----------------------------------------------------

[1]

TÍTULO / TITLE:  - Impact of FOLFIRINOX Compared With Gemcitabine on Quality of Life in Patients With Metastatic Pancreatic Cancer: Results From the PRODIGE 4/ACCORD 11 Randomized Trial.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 1;31(1):23-9. doi: 10.1200/JCO.2012.44.4869. Epub 2012 Dec 3.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.4869

AUTORES / AUTHORS:  - Gourgou-Bourgade S; Bascoul-Mollevi C; Desseigne F; Ychou M; Bouche O; Guimbaud R; Becouarn Y; Adenis A; Raoul JL; Boige V; Berille J; Conroy T

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Centre Alexis Vautrin, 6 avenue de Bourgogne, Vandoeuvre-les-Nancy CEDEX, France CS 305; t.conroy@nancy.unicancer.fr.

RESUMEN / SUMMARY:  - PURPOSE To compare the quality of life (QoL) of patients receiving oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) or gemcitabine as first-line chemotherapy and to assess whether pretreatment QoL predicts survival  in patients with metastatic pancreatic cancer. PATIENTS AND METHODS Three hundred forty-two patients with performance status 0 or 1 were randomly assigned to receive FOLFIRINOX (oxaliplatin, 85 mg/m(2); irinotecan, 180 mg/m(2); leucovorin, 400 mg/m(2); and fluorouracil, 400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-hour continuous infusion, once every 2 weeks) or gemcitabine 1,000 mg/m(2) weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. QoL was assessed using  European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30 every 2 weeks. Results Improvement in global health status (GHS; P < .001) was observed in the FOLFIRINOX arm and improvement in emotional functioning (P < .001) was observed in both arms, along with a decrease in pain,  insomnia, anorexia, and constipation in both arms. A significant increase in diarrhea was observed in the FOLFIRINOX arm during the first 2 months of chemotherapy. Time until definitive deterioration >/= 20 points was significantly longer for FOLFIRINOX compared with gemcitabine for GHS, physical, role, cognitive, and social functioning, and six symptom domains (fatigue, nausea/vomiting, pain, dyspnea, anorexia, and constipation). Physical functioning, constipation, and dyspnea were independent significant prognostic factors for survival with treatment arm, age older than 65 years, and low serum albumin. CONCLUSION FOLFIRINOX significantly reduces QoL impairment compared with gemcitabine in patients with metastatic pancreatic cancer. Furthermore, baseline  QoL scores improved estimation of survival probability when added to baseline clinical and demographic variables.

 

----------------------------------------------------

[2]

TÍTULO / TITLE:  - Survival Is Associated With Genetic Variation in Inflammatory Pathway Genes Among Patients With Resected and Unresected Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e318275b7e5

AUTORES / AUTHORS:  - Reid-Lombardo KM; Fridley BL; Bamlet WR; Cunningham JM; Sarr MG; Petersen GM

INSTITUCIÓN / INSTITUTION:  - *Division of Gastroenterologic and General Surgery daggerDivision of Biomedical Statistics and Informatics double daggerDepartment of Laboratory Medicine and Pathology section signDivision of Epidemiology at Mayo Clinic, Rochester, MN.

RESUMEN / SUMMARY:  - OBJECTIVE:: To test whether or not the association between inflammation and pancreatic ductal adenocarcinoma (PC) is facilitated by host susceptibility, specifically by genetic polymorphisms in inflammation-related genes. SUMMARY BACKGROUND DATA:: Inflammation has been linked to PC. Reports have cited an increased expression of proinflammatory mediators, such as NF-kappaB and COX, in  PC but not in normal adjacent tissue, suggesting a possible role in carcinogenesis. We sought to further understand the role that genetic variants in the NF-kappaB inflammatory pathway play in the development and progression of PC. METHODS:: We genotyped 1536 tag single nucleotide polymorphisms (SNPs) in 102 candidate genes of multiple inflammatory pathways in 1308 white patients with PC  who were divided into 3 groups on the basis of the extent of disease: resected for cure (n = 400), locally advanced/unresected (n = 443), and metastatic (n = 465). Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards regression models. Statistical significance was set at less  than 0.001 to control for multiple testing. RESULTS:: Median age was 67 (28.0-91.0) years, and 57% were men. Median survival for each of the 3 groups (resected, locally advanced, and metastatic) was 23.7, 9.4, and 6.6 months, respectively (P < 0.0001). In the resected group, carriers of a minor allele for  either rs3824872 (MAPK8IP1) or rs8064821 (SOCS3) were associated with a 10- and 6-month survival advantage compared with noncarriers in patients with resected disease, with an additional 2-year survival if both minor alleles were present. With locally advanced disease, SNP rs1124736 (IGF1R) was associated with improved survival if they had a copy of the G allele, hazard ratio of 0.57 (95% confidence interval: 0.42-0.77); P = 0.0002. In addition, 4 SNPs in patients with metastatic disease were found to be associated with worse survival and 2 associated with improved overall survival, but the differences in survival were deemed not clinically significant. CONCLUSIONS:: SNPs in the inflammatory pathway genes MAPK8IP1 and SOCS3 were associated with increased overall survival in patients undergoing potentially curative resection and may be used in the future as markers to predict survival. Future research is needed to determine the functional relevance of these loci.

 

----------------------------------------------------

[3]

TÍTULO / TITLE:  - The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Genes Dev. 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 1101/gad.204453.112

AUTORES / AUTHORS:  - Reichert M; Takano S; von Burstin J; Kim SB; Lee JS; Ihida-Stansbury K; Hahn C; Heeg S; Schneider G; Rhim AD; Stanger BZ; Rustgi AK

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology.

RESUMEN / SUMMARY:  - Pancreatic exocrine cell plasticity can be observed during development, pancreatitis with subsequent regeneration, and also transformation. For example,  acinar-ductal metaplasia (ADM) occurs during acute pancreatitis and might be viewed as a prelude to pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) development. To elucidate regulatory processes that overlap ductal development, ADM, and the progression of normal cells to PanIN lesions, we undertook a systematic approach to identify the Prrx1  paired homeodomain Prrx1 transcriptional factor as a highly regulated gene in these processes. Prrx1 annotates a subset of pancreatic ductal epithelial cells in Prrx1creER(T2)-IRES-GFP mice. Furthermore, sorted Prrx1(+) cells have the capacity to self-renew and expand during chronic pancreatitis. The two isoforms,  Prrx1a and Prrx1b, regulate migration and invasion, respectively, in pancreatic cancer cells. In addition, Prrx1b is enriched in circulating pancreatic cells (Pdx1cre;LSL-Kras(G12D/+);p53(fl/+);R26YFP). Intriguingly, the Prrx1b isoform, which is also induced in ADM, binds the Sox9 promoter and positively regulates Sox9 expression. This suggests a new hierarchical scheme whereby a Prrx1-Sox9 axis may influence the emergence of acinar-ductal metaplasia and regeneration. Furthermore, our data provide a possible explanation of why pancreatic cancer is  skewed toward a ductal fate.

 

----------------------------------------------------

[4]

TÍTULO / TITLE:  - Vaccination with ENO1 DNA Prolongs Survival of Genetically Engineered Mice with Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastroenterology. 2013 Jan 16. pii: S0016-5085(13)00077-2. doi: 10.1053/j.gastro.2013.01.020.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.gastro.2013.01.020

AUTORES / AUTHORS:  - Cappello P; Rolla S; Chiarle R; Principe M; Cavallo F; Perconti G; Feo S; Giovarelli M; Novelli F

INSTITUCIÓN / INSTITUTION:  - Center for Experimental Research and Medical Studies (CERMS), Citta della Salute  e della Scienza di Torino; Department of Molecular Biotechnology and Health Science, University of Torino, 10125 Torino, Italy.

RESUMEN / SUMMARY:  - BACKGROUND & AIMS:: Pancreatic ductal adenocarcinoma (PDA) is an aggressive tumor, and patients typically present with late-stage disease; rates of 5-year survival after pancreaticoduodenectomy are low. Antibodies against -enolase (ENO1), a glycolytic enzyme, are detected in more than 60% of patients with PDA,  and ENO1-specific T cells inhibit the growth of human pancreatic xenograft tumors in mice. We investigated whether an ENO1DNA vaccine elicits anti-tumor immune responses and prolongs survival of mice that spontaneously develop autochthonous, lethal pancreatic carcinomas. METHODS:: We injected and electroporated a plasmid  encoding ENO1 (or a control plasmid) into Kras(G12D)/Cre mice (KC) and Kras(G12D)/Trp53 (R172H) /Cre (KPC) mice when they were 4 weeks old (when pancreatic intraepithelial lesions are histologically evident). Anti-tumor humoral and cellular responses were analyzed by histology, immunohistochemistry,  ELISAs, flow cytometry, and ELISpot and cytotoxicity assays. Survival was analyzed by Kaplan-Meier analysis. RESULTS:: The ENO1 vaccine induced antibody and a cellular responses and increased survival times by a median 138 days in KC  mice and 42 days in KPC mice, compared with mice given the control vector. In histologic analysis, the vaccine appeared to slow tumor progression. The vaccinated mice had increased serum levels of anti-ENO1 immunoglobulin G, which bound the surface of carcinoma cells and induced complement-dependent cytotoxicity. ENO1 vaccination reduced numbers of myeloid-derived suppressor cells and T-regulatory cells, and increased T-helper 1 and 17 responses. CONCLUSIONS:: In a genetic model of pancreatic carcinoma, vaccination with ENO1DNA elicits humoral and cellular immune responses against tumors, delays tumor progression, and significantly extends survival. This vaccination strategy  might be developed as a neo-adjuvant therapy for patients with PDA.

 

----------------------------------------------------

[5]

TÍTULO / TITLE:  - Concomitant Vascular Reconstruction During Pancreatectomy for Malignant Disease:  A Propensity Score-Adjusted, Population-Based Trend Analysis Involving 10 206 Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Surg. 2012 Dec 17:1-8. doi: 10.1001/jamasurg.2013.1058.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jamasurg.2013.1058

AUTORES / AUTHORS:  - Worni M; Castleberry AW; Clary BM; Gloor B; Carvalho E; Jacobs DO; Pietrobon R; Scarborough JE; White RR

RESUMEN / SUMMARY:  - OBJECTIVE To assess trends in the frequency of concomitant vascular reconstructions (VRs) from 2000 through 2009 among patients who underwent pancreatectomy, as well as to compare the short-term outcomes between patients who underwent pancreatic resection with and without VR. DESIGN Single-center series have been conducted to evaluate the short-term and long-term outcomes of VR during pancreatic resection. However, its effectiveness from a population-based perspective is still unknown. Unadjusted, multivariable, and propensity score-adjusted generalized linear models were performed. SETTING Nationwide Inpatient Sample from 2000 through 2009. PATIENTS A total of 10 206 patients were involved. MAIN OUTCOME MEASURES Incidence of VR during pancreatic resection, perioperative in-hospital complications, and length of hospital stay.  RESULTS Overall, 10 206 patients were included in this analysis. Of these, 412 patients (4.0%) underwent VR, with the rate increasing from 0.7% in 2000 to 6.0%  in 2009 (P &lt; .001). Patients who underwent pancreatic resection with VR were at a higher risk for intraoperative (propensity score-adjusted odds ratio, 1.94;  P = .001) and postoperative (propensity score-adjusted odds ratio, 1.36; P = .008) complications, while the mortality and median length of hospital stay were  similar to those of patients without VR. Among the 25% of hospitals with the highest surgical volume, patients who underwent pancreatic surgery with VR had significantly higher rates of postoperative complications and mortality than patients without VR. CONCLUSIONS The frequency of VR during pancreatic surgery is increasing in the United States. In contrast with most single-center analyses, this population-based study demonstrated that patients who underwent VR during pancreatic surgery had higher rates of adverse postoperative outcomes than their  counterparts who underwent pancreatic resection only. Prospective studies incorporating long-term outcomes are warranted to further define which patients benefit from VR.

 

----------------------------------------------------

[6]

TÍTULO / TITLE:  - Combined analysis of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression is a powerful predictor of survival in patients with pancreatic carcinoma treated with adjuvant gemcitabine-based chemotherapy after operative resection.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surgery. 2012 Dec 17. pii: S0039-6060(12)00628-9. doi: 10.1016/j.surg.2012.10.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2012.10.010

AUTORES / AUTHORS:  - Nakagawa N; Murakami Y; Uemura K; Sudo T; Hashimoto Y; Kondo N; Sueda T

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: naoyaman423@hiroshima-u.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: Although postoperative adjuvant chemotherapy for pancreatic carcinoma improves survival in some patients, its efficacy varies among individuals. The aim of this study was to determine the usefulness of intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) as predictive markers of the efficacy of adjuvant gemcitabine-based chemotherapy for pancreatic carcinoma after operative resection. METHODS: The expression of intratumoral hENT1 and RRM1 was examined immunohistochemically in 109 patients with pancreatic carcinoma who received adjuvant gemcitabine-based chemotherapy after operative resection. Relationships  between clinicopathologic factors, including hENT1 and RRM1 expression, and disease-free and overall survival (DFS and OS) were evaluated by univariate and multivariate analyses. RESULTS: The 5-year DFS and OS rates for the 109 patients  were 26% and 31%, respectively. In univariate analysis, both hENT1 and RRM1 expression were significantly associated with DFS (hENT1, P = .004; RRM1, P = .011) and OS (hENT1, P = .001; RRM1, P = .040). In multivariate analysis, both were independent factors for DFS (hENT1, P = .001; RRM1, P = .009) and OS (hENT1, P = .001, RRM1, P = .019). Evaluation of the combination analysis of both was also identified as a powerful independent predictor of DFS (P < .001) and OS (P < .001). CONCLUSION: Expression of hENT1 and RRM1 is predictive of the efficacy of  adjuvant gemcitabine-based chemotherapy for pancreatic carcinoma after operative  resection. In addition, their combined analysis has greater predictive value than either factor alone.

 

----------------------------------------------------

[7]

TÍTULO / TITLE:  - A Prospective Study of Plasma Adiponectin and Pancreatic Cancer Risk in Five US Cohorts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Natl Cancer Inst. 2013 Jan 16;105(2):95-103. doi: 10.1093/jnci/djs474. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/jnci/djs474

AUTORES / AUTHORS:  - Bao Y; Giovannucci EL; Kraft P; Stampfer MJ; Ogino S; Ma J; Buring JE; Sesso HD; Lee IM; Gaziano JM; Rifai N; Pollak MN; Cochrane BB; Kaklamani V; Lin JH; Manson JE; Fuchs CS; Wolpin BM

INSTITUCIÓN / INSTITUTION:  - Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115. ying.bao@channing.harvard.edu.

RESUMEN / SUMMARY:  - Background The adipocyte-secreted hormone adiponectin has insulin-sensitizing and anti-inflammatory properties. Although development of pancreatic cancer is associated with states of insulin resistance and chronic inflammation, the mechanistic basis of the associations is poorly understood. Methods To determine  whether prediagnostic plasma levels of adiponectin are associated with risk of pancreatic cancer, we conducted a nested case-control study of 468 pancreatic cancer case subjects and 1080 matched control subjects from five prospective US cohorts: Health Professionals Follow-up Study, Nurses’ Health Study, Physicians’  Health Study, Women’s Health Initiative, and Women’s Health Study. Control subjects were matched to case subjects by prospective cohort, year of birth, smoking status, fasting status, and month of blood draw. All samples for plasma adiponectin were handled identically in a single batch. Odds ratios were calculated with conditional logistic regression, and linearity of the association between adiponectin and pancreatic cancer was modeled with restricted cubic spline regression. All statistical tests were two-sided. Results Median plasma adiponectin was lower in case subjects versus control subjects (6.2 vs 6.8 microg/mL, P = .009). Plasma adiponectin was inversely associated with pancreatic cancer risk, which was consistent across the five prospective cohorts (P (heterogeneity) = .49) and independent of other markers of insulin resistance (eg, diabetes, body mass index, physical activity, plasma C-peptide). Compared with the lowest quintile of adiponectin, individuals in quintiles 2 to 5 had multivariable odds ratios ([ORs] 95% confidence intervals [CIs]) of OR = 0.61 (95% CI = 0.43 to 0.86), OR = 0.58 (95% CI = 0.41 to 0.84), OR = 0.59 (95% CI = 0.40 to 0.87), and OR = 0.66 (95% CI = 0.44 to 0.97), respectively (P (trend) = .04). Restricted cubic spline regression confirmed a nonlinear association (P (nonlinearity) < .01). The association was not modified by sex, smoking, body mass index, physical activity, or C-peptide (all P (interaction) > .10). Conclusions In this pooled analysis, low prediagnostic levels of circulating adiponectin were associated with an elevated risk of pancreatic cancer.

 

----------------------------------------------------

[8]

TÍTULO / TITLE:  - Identifying people at a high risk of developing pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Cancer. 2013 Jan;13(1):66-74. doi: 10.1038/nrc3420. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrc3420

AUTORES / AUTHORS:  - Klein AP

INSTITUCIÓN / INSTITUTION:  - Departments of Oncology and Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA. aklein1@jhmi.edu.

RESUMEN / SUMMARY:  - Pancreatic cancer is a leading cause of cancer death, and it has the poorest prognosis of any major tumour type. Familial pancreatic cancer registries are important for investigating the genetic aetiology of this devastating disease. Using data from our familial pancreatic cancer registry and other registries, this Review discusses the usefulness of family registries in the study of pancreatic and other cancers, and also how such registries provide a unique opportunity for laboratory, population and clinical research.

 

----------------------------------------------------

[9]

TÍTULO / TITLE:  - Randomized Phase III Multi-Institutional Study of TNFerade Biologic With Fluorouracil and Radiotherapy for Locally Advanced Pancreatic Cancer: Final Results.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.7516

AUTORES / AUTHORS:  - Herman JM; Wild AT; Wang H; Tran PT; Chang KJ; Taylor GE; Donehower RC; Pawlik TM; Ziegler MA; Cai H; Savage DT; Canto MI; Klapman J; Reid T; Shah RJ; Hoffe SE; Rosemurgy A; Wolfgang CL; Laheru DA

INSTITUCIÓN / INSTITUTION:  - Joseph M. Herman, Aaron T. Wild, Hao Wang, Phuoc T. Tran, Gretchen E. Taylor, Ross C. Donehower, Timothy M. Pawlik, Mark A. Ziegler, Hongyan Cai, Dionne T. Savage, Christopher L. Wolfgang, and Daniel A. Laheru, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine; Marcia  I. Canto, Johns Hopkins University School of Medicine, Baltimore, MD; Kenneth J.  Chang, H.H. Chao Comprehensive Digestive Disease Center, University of California Irvine Medical Center, Orange; Tony Reid, Rebecca and John Moores Cancer Center,  University of California San Diego School of Medicine, La Jolla, CA; Jason Klapman, Sarah E. Hoffe, Alexander Rosemurgy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; and Raj J. Shah, University of Colorado School of  Medicine, Aurora, CO.

RESUMEN / SUMMARY:  - PURPOSETNFerade biologic is a novel means of delivering tumor necrosis factor alpha to tumor cells by gene transfer. We herein report final results of the largest randomized phase III trial performed to date among patients with locally  advanced pancreatic cancer (LAPC) and the first to test gene transfer against this malignancy.Patients And methodsIn all, 304 patients were randomly assigned 2:1 to standard of care plus TNFerade (SOC + TNFerade) versus standard of care alone (SOC). SOC consisted of 50.4 Gy in 28 fractions with concurrent fluorouracil (200 mg/m(2) per day continuous infusion). TNFerade was injected intratumorally before the first fraction of radiotherapy each week at a dose of 4 x 10(11) particle units by using either a percutaneous transabdominal or an endoscopic ultrasound approach. Four weeks after chemoradiotherapy, patients began gemcitabine (1,000 mg/m(2) intravenously) with or without erlotinib (100 to 150 mg per day orally) until progression or toxicity.ResultsThe analysis included 187 patients randomly assigned to SOC + TNFerade and 90 to SOC by using a modified intention-to-treat approach. Median follow-up was 9.1 months (range, 0.1 to 50.5 months). Median survival was 10.0 months for patients in both the SOC + TNFerade and SOC arms (hazard ratio [HR], 0.90; 95% CI, 0.66 to 1.22; P = .26). Median progression-free survival (PFS) was 6.8 months for SOC + TNFerade versus 7.0 months for SOC (HR, 0.96; 95% CI, 0.69 to 1.32; P = .51). Among patients treated on the SOC + TNFerade arm, multivariate analysis showed that TNFerade injection by an endoscopic ultrasound-guided transgastric/transduodenal approach  rather than a percutaneous transabdominal approach was a risk factor for inferior PFS (HR, 2.08; 95% CI, 1.06 to 4.06; P = .032). The patients in the SOC + TNFerade arm experienced more grade 1 to 2 fever and chills than those in the SOC arm (P < .001) but both arms had similar rates of grade 3 to 4 toxicities (all P  > .05). CONCLUSIONSOC + TNFerade is safe but not effective for prolonging survival in patients with LAPC.

 

----------------------------------------------------

[10]

TÍTULO / TITLE:  - Plasma adiponectin: a possible link between fat metabolism and pancreatic cancer  risk.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Natl Cancer Inst. 2013 Jan 16;105(2):79-80. doi: 10.1093/jnci/djs522. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/jnci/djs522

AUTORES / AUTHORS:  - Zhang J; Hochwald SN

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. steven.hochwald@roswellpark.org.

 

----------------------------------------------------

[11]

TÍTULO / TITLE:  - Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Exp Immunol. 2013 Jan;171(1):82-90. doi: 10.1111/j.1365-2249.2012.04675.x.

            ●● Enlace al texto completo (gratuito o de pago) 1111/j.1365-2249.2012.04675.x

AUTORES / AUTHORS:  - Gorus FK; Balti EV; Vermeulen I; Demeester S; Van Dalem A; Costa O; Dorchy H; Tenoutasse S; Mouraux T; De Block C; Gillard P; Decochez K; Wenzlau JM; Hutton JC; Pipeleers DG; Weets I

INSTITUCIÓN / INSTITUTION:  - Diabetes Research Center, Brussels Free University, Brussels, Belgium.

RESUMEN / SUMMARY:  - In first-degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA-2) and zinc transporter 8 (ZnT8) antibody status (IA-2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies [antibodies against insulin (IAA),  glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA-2A with or without ZnT8A] in identifying children, adolescents and  adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow-up of 6444 siblings and offspring aged 0-39 years at inclusion and recruited consecutively by the Belgian Diabetes  Registry. We identified 394 persistently IAA(+) , GADA(+) , IA-2A(+) and/or ZnT8A(+) relatives (6.1%). After a median follow-up time of 52 months, 132 relatives developed type 1 diabetes. In each age category tested (0-9, 10-19 and  20-39 years) progression to diabetes was significantly quicker in the presence of IA-2A and/or ZnT8A than in their joint absence (P < 0.001). Progression rate was  age-independent in IA-2A(+) and/or ZnT8A(+) relatives but decreased with age if only GADA and/or IAA were present (P = 0.008). In the age group mainly considered for immune interventions until now (10-39 years), screening for IA-2A and ZnT8A alone identified 78% of the rapid progressors (versus 75% if positive for >/= 2 antibodies among IAA, GADA, IA-2A and ZnT8A or versus 62% without testing for ZnT8A). Screening for IA-2A and ZnT8A alone allows identification of the majority of rapidly progressing prediabetic siblings and offspring regardless of age and is more cost-effective to select participants for intervention trials than conventional screening.

 

----------------------------------------------------

[12]

TÍTULO / TITLE:  - KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Invest. 2013 Jan 16. pii: 64535. doi: 10.1172/JCI64535.

            ●● Enlace al texto completo (gratuito o de pago) 1172/JCI64535

AUTORES / AUTHORS:  - Tzatsos A; Paskaleva P; Ferrari F; Deshpande V; Stoykova S; Contino G; Wong KK; Lan F; Trojer P; Park PJ; Bardeesy N

RESUMEN / SUMMARY:  - Epigenetic mechanisms mediate heritable control of cell identity in normal cells  and cancer. We sought to identify epigenetic regulators driving the pathogenesis  of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers. We found that KDM2B (also known as Ndy1, FBXL10, and JHDM1B), an H3K36 histone demethylase implicated in bypass of cellular senescence and somatic cell reprogramming, is markedly overexpressed in human PDAC, with levels increasing with disease grade and stage, and highest expression in metastases. KDM2B silencing abrogated tumorigenicity of PDAC cell lines exhibiting loss of epithelial differentiation, whereas KDM2B overexpression cooperated with KrasG12D to promote PDAC formation in mouse models. Gain- and loss-of-function experiments coupled to genome-wide gene expression and ChIP studies revealed that KDM2B drives tumorigenicity through 2 different transcriptional mechanisms. KDM2B repressed developmental genes through cobinding with Polycomb group (PcG) proteins at transcriptional start sites, whereas it activated a module of metabolic genes, including mediators of protein synthesis and mitochondrial function, cobound by the MYC oncogene and the histone demethylase KDM5A. These results defined epigenetic programs through which KDM2B subverts cellular differentiation and drives the pathogenesis of an aggressive subset of PDAC.

 

----------------------------------------------------

[13]

TÍTULO / TITLE:  - Phase I trial of gemcitabine combined with capecitabine and erlotinib in advanced pancreatic cancer: a clinical and pharmacological study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chemotherapy. 2012;58(5):371-80. doi: 10.1159/000343969. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000343969

AUTORES / AUTHORS:  - Francois E; Bennouna J; Chamorey E; Etienne-Grimaldi MC; Renee N; Senellart H; Michel C; Follana P; Mari V; Douillard JY; Milano G

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Antoine Lacassagne Cancer Research Center, Nice,  France.

RESUMEN / SUMMARY:  - Background: The aim of this phase I trial was to define the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT) and the recommended dose of erlotinib combined with capecitabine and gemcitabine in the treatment of advanced pancreatic cancer (APC). Methods: Gemcitabine was administered intravenously at 1,000 mg/m(2)/week (days 1, 8 and 15) and oral capecitabine from day 1 to day 21  at 1,660 mg/m(2)/day. Oral erlotinib was administered daily continuously at escalating doses (28-day cycle). Dose levels (DLs) 1, 2, 3 and 4 were 50, 75, 100 and 125 mg/day, respectively. Pharmacokinetic analysis of the three drugs was performed in the first cycle. Results: Nineteen patients were enrolled. At the MTD (DL4; 125 mg/day erlotinib), 100% of patients developed DLT consisting of grade 4 febrile neutropenia and nonhematological grade 3 events (vomiting, diarrhea, stomatitis, rash). The most common toxicities, regardless of grade, were neutropenia, anemia, rash and diarrhea. Erlotinib systemic exposure was significantly related to the administered dose. Of note, toxicity was significantly associated with elevated systemic exposure of capecitabine anabolites. Conclusion: When combined concurrently with 1,000 mg/m(2)/week gemcitabine and 1,660 mg/m(2)/day capecitabine, erlotinib can be administered safely at a daily dose of 100 mg in APC patients.

 

----------------------------------------------------

[14]

TÍTULO / TITLE:  - Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase ½ Dose Escalation Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2012 Dec 19. pii: S0360-3016(12)03817-5. doi: 10.1016/j.ijrobp.2012.11.020.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.11.020

AUTORES / AUTHORS:  - Vainshtein JM; Schipper M; Zalupski MM; Lawrence TS; Abrams R; Francis IR; Khan G; Leslie W; Ben-Josef E

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. Electronic address: jvainsh@med.umich.edu.

RESUMEN / SUMMARY:  - PURPOSE: Although established in the postresection setting, the prognostic value  of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. METHODS AND MATERIALS: Forty-six patients with unresectable LAPC were treated at  the University of Michigan on a phase ½ trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. RESULTS: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and  female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 </=90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88,  P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90  U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and  it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). CONCLUSIONS: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.

 

----------------------------------------------------

[15]

TÍTULO / TITLE:  - Pancreatic cancer: Tracing origins.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Cancer. 2013 Jan;13(1):5. doi: 10.1038/nrc3439.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrc3439

AUTORES / AUTHORS:  - Seton-Rogers S

 

----------------------------------------------------

[16]

TÍTULO / TITLE:  - Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 17. doi: 10.1038/bjc.2012.546.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2012.546

AUTORES / AUTHORS:  - Kawaguchi T; Komatsu S; Ichikawa D; Morimura R; Tsujiura M; Konishi H; Takeshita H; Nagata H; Arita T; Hirajima S; Shiozaki A; Ikoma H; Okamoto K; Ochiai T; Taniguchi H; Otsuji E

INSTITUCIÓN / INSTITUTION:  - Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.

RESUMEN / SUMMARY:  - Background:Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We tested miR-221 and miR-375, which are frequently reported to be highly and poorly expressed in pancreatic cancer (PCa), as candidates for plasma biomarkers in PCa.Methods:This study was divided into three parts: (1) Confirmation of higher miR-221 levels in primary PCa tissue and  cell lines than normal pancreatic tissues. (2) Evaluation of plasma miR-221 and miR-375 concentrations by comparing results from 47 consecutive PCa patients and  30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in PCa patients.Results:(1) Expression of miR-221 was significantly higher in PCa tissues and cell lines than normal pancreatic tissues. (2) Plasma miR-221 concentrations were significantly higher in PCa patients than that in benign pancreatic tumours (P=0.016) and controls (P<0.0005), while plasma miR-375 concentrations tended to be lower in PCa patients (P=0.064), and the miR-221/miR-375 ratio was significantly higher (P<0.0001) in PCa patients than in controls. (3) Plasma miR-221 concentrations were significantly reduced in postoperative samples (P=0.018). Furthermore, PCa patients with high plasma miR-221 concentrations had significant correlation with distant metastasis (P=0.041), and non-resectable status (P=0.021).Conclusion:Plasma miR-221 could be a useful biomarker for cancer detection, monitoring tumour dynamics and predicting malignant outcomes in PCa patients, and may contribute to clinical decision making in PCa treatments.British Journal of Cancer advance online publication, 17 January 2013; doi:10.1038/bjc.2012.546 www.bjcancer.com.

 

----------------------------------------------------

[17]

TÍTULO / TITLE:  - Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cancer Res Clin Oncol. 2013 Jan 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00432-012-1371-3

AUTORES / AUTHORS:  - Haas M; Heinemann V; Kullmann F; Laubender RP; Klose C; Bruns CJ; Holdenrieder S; Modest DP; Schulz C; Boeck S

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377,  Munich, Germany.

RESUMEN / SUMMARY:  - PURPOSE: CA 19-9 is the only established tumor marker in pancreatic cancer (PC);  the prognostic role of other serum markers like CEA, CRP, LDH or bilirubin has not yet been defined. METHODS: We pooled pre-treatment data on CA 19-9, CEA, CRP, LDH and bilirubin levels from two German multicenter randomized phase II trials together with prospective patient data from one high-volume German Cancer Center. Marker levels were assessed locally before the start of palliative first-line therapy for advanced PC and serially during treatment (for CA 19-9 only). Clinical and biomarker data (overall 12 variables) were correlated with the efficacy endpoints time-to-progression (TTP) and overall survival (OS) by using uni- and multivariate Cox models. RESULTS: Data from 291 patients were included in this pooled analysis; 253 patients (87 %) received treatment within prospective clinical trials. Median TTP in the study cohort was 5.1 months and median OS 9.0 months. In univariate analysis, pre-treatment CA 19-9 (HR 1.55), LDH (HR 2.04) and CEA (HR 1.89) levels were significantly associated with TTP. Regarding OS, baseline CA 19-9 (HR 1.46), LDH (HR 2.07), CRP (HR 1.69) and bilirubin (HR 1.62) were significant prognostic factors. Within multivariate analyses, pre-treatment log [CA 19-9] (as continuous variable for TTP) and log [bilirubin] as well as log [CRP] (for OS) had an independent prognostic value. A  CA 19-9 decline of >/=25 % during the first two chemotherapy cycles was predictive for TTP and OS, independent of the applied CA 19-9 assay. CONCLUSION:  Baseline CA 19-9 and CA 19-9 kinetics during first-line chemotherapy are prognostic in advanced PC. Besides that finding other serum markers like CRP, LDH and bilirubin can also provide prognostic information on TTP and OS.

 

----------------------------------------------------

[18]

TÍTULO / TITLE:  - A patient with retroperitoneal fibrosis treated with tamoxifen who develops pancreatic carcinoma: remarks regarding the presence of estrogen receptors-a relationship between fibrosis and neoplastic processes?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2013 Jan;42(1):174-5. doi: 10.1097/MPA.0b013e318255adec.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318255adec

AUTORES / AUTHORS:  - Velciov S; Gluhovschi C; Petrica L; Gluhovschi A

INSTITUCIÓN / INSTITUTION:  - Department of Nephrology County Emergency Hospital Timisoara “V. Babes” University of Medicine and Pharmacy Timisoara, Romania s_velciov@yahoo.com Department of Obstetrics and Gynecology County Emergency Hospital Timisoara “V. Babes” University of Medicine and Pharmacy Timisoara, Romania.

 

----------------------------------------------------

[19]

TÍTULO / TITLE:  - Unresectable locally advanced pancreatic cancer: treatment with neoadjuvant leucovorin, Fluorouracil, irinotecan, and oxaliplatin and assessment of surgical  resectability.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 20;31(3):e37-9. doi: 10.1200/JCO.2012.44.0339. Epub 2012 Dec 10.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.0339

AUTORES / AUTHORS:  - Mondo EL; Noel MS; Katz AW; Schoeniger LO; Hezel AF

INSTITUCIÓN / INSTITUTION:  - James P. Wilmot Cancer Center, University of Rochester Medical Center School of Medicine and Dentistry, 601 Elmwood Ave, Box 704, Rochester, NY 14642; Aram_Hezel@URMC.Rochester.edu.

 

----------------------------------------------------

[20]

TÍTULO / TITLE:  - Pancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Med Genet. 2013 Jan;50(1):59-64. doi: 10.1136/jmedgenet-2012-101277.

            ●● Enlace al texto completo (gratuito o de pago) 1136/jmedgenet-2012-101277

AUTORES / AUTHORS:  - Korsse SE; Harinck F; van Lier MG; Biermann K; Offerhaus GJ; Krak N; Looman CW; van Veelen W; Kuipers EJ; Wagner A; Dekker E; Mathus-Vliegen EM; Fockens P; van Leerdam ME; Bruno MJ

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology & Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands. s.korsse@erasmusmc.nl

RESUMEN / SUMMARY:  - BACKGROUND: Although Peutz-Jeghers syndrome (PJS) is known to be associated with  pancreatic cancer (PC), estimates of this risk differ widely. This hampers counselling of patients and implementation of surveillance strategies. We therefore aimed to determine the PC risk in a large cohort of Dutch PJS patients. METHODS: PJS was defined by diagnostic criteria recommended by the WHO, a proven  LKB1 mutation, or both. All patients with a presumptive diagnosis of pancreatic,  ampullary or distal bile duct cancer were identified. Cases were reviewed clinically, radiologically and immunohistochemically. Cumulative PC risks were calculated by Kaplan-Meier analysis and relative risks by Poisson regression analysis. RESULTS: We included 144 PJS patients (49% male) from 61 families (5640 person years follow-up). Seven (5%) patients developed PC at a median age of 54 years. Four patients (3%) were diagnosed with distal bile duct (n=2) or ampullary cancer (n=2) at a median age of 55 years. The cumulative risk for PC was 26% (95% CI 4% to 47%) at age 70 years and relative risk was 76 (95% CI 36 to 160; p<0.001). The cumulative risk for pancreatico-biliary cancer was 32% (95% CI 11%  to 52%) at age 70 years, with a relative risk of 96 (95% CI 53 to 174; p<0.001).  CONCLUSIONS: PJS patients have a highly increased risk for pancreatico-biliary cancer. Therefore, patients are eligible for surveillance within well defined research programmes to establish the benefit of such surveillance.

 

----------------------------------------------------

[21]

TÍTULO / TITLE:  - Genetic Alterations of K-ras, p53, c-erbB-2, and DPC4 in Pancreatic Ductal Adenocarcinoma and Their Correlation With Patient Survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31825b6ab0

AUTORES / AUTHORS:  - Shin SH; Kim SC; Hong SM; Kim YH; Song KB; Park KM; Lee YJ

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Surgery and daggerPathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

RESUMEN / SUMMARY:  - OBJECTIVES: The objective of this study was to evaluate genetic alterations of K-ras, p53, c-erbB-2, and deleted in pancreatic cancer, locus 4 (DPC4) genes in pancreatic ductal adenocarcinoma and correlate these changes with patients’ overall survival. METHODS: Between April 2004 and December 2008, 272 patients with pancreatic ductal adenocarcinoma underwent surgical resection at a single institute. Genetic analyses and immunohistochemical stains were reviewed retrospectively. RESULTS: Alterational rates of each gene were as follows: K-ras, 53.8%; p53, 38.2%; c-erbB-2, 7.3%; DPC4, 81.6%. Subtypes of K-ras gene were as follows: GGT (wild type), 46.2%; GAT, 31.2%; GTT, 14.5%; CGT, 5.6%; TGT, 1.7%; CTG, 0.4%; AGT, 0.4%. K-ras mutation (especially GAT subtype) and DPC4 inactivation resulted in a reduction of postresection survival (P = 0.001 and P = 0.047). Univariate analysis revealed 8 factors affecting to the survival, and multivariate analysis revealed that 6 of them were independently responsible for  poor survival of patients: presence of lymphovascular tumor emboli, DPC4 inactivation, poorly differentiated carcinoma, K-ras mutation, presence of lymph  node metastasis, and elevated CA-19-9 (>37 U/mL). CONCLUSIONS: This study may help to understand the genetic feature of pancreatic cancer and its survival effect in our population. This shows that additional genetic insights would contribute to the improvement of patients’ prognosis.

 

----------------------------------------------------

[22]

TÍTULO / TITLE:  - The use of a novel MUC1 antibody to identify cancer stem cells and circulating MUC1 in mice and patients with pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Surg Oncol. 2013 Jan 17. doi: 10.1002/jso.23316.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jso.23316

AUTORES / AUTHORS:  - Curry JM; Thompson KJ; Rao SG; Besmer DM; Murphy AM; Grdzelishvili VZ; Ahrens WA; McKillop IH; Sindram D; Iannitti DA; Martinie JB; Mukherjee P

INSTITUCIÓN / INSTITUTION:  - Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVES: MUC1 is over-expressed and aberrantly glycosylated in  >60% of human pancreatic cancer (PC). Development of novel approaches for detection and/or targeting of MUC1 are critically needed and should be able to detect MUC1 on PC cells (including cancer stem cells) and in serum. METHODS: The  sensitivity and specificity of the anti-MUC1 antibody, TAB 004, was determined. CSCs were assessed for MUC1 expression using TAB 004-FITC on in vitro PC cell lines, and on lineage(-) cells from in vivo tumors and human samples. Serum was assessed for shed MUC1 via the TAB 004 EIA. RESULTS: In vitro and in vivo, TAB 004 detected MUC1 on >95% of CSCs. Approximately, 80% of CSCs in patients displayed MUC1 expression as detected by TAB 004. Shed MUC1 was detected serum in mice with HPAF-II (MUC1(high) ) but not BxPC3 tumors (MUC1(low) ). The TAB 004 EIA was able to accurately detect stage progression in PC patients. CONCLUSIONS:  The TAB 004 antibody may be explored as a therapeutic targeting agent for CSCs in PC. The TAB 004 EIA detected circulating MUC1 in a stage-dependent manner in patients with PC and thus may be explored as a PC stage diagnostic biomarker. J.  Surg. Oncol © 2013 Wiley Periodicals, Inc.

 

----------------------------------------------------

[23]

TÍTULO / TITLE:  - The receptor for advanced glycation end products promotes pancreatic carcinogenesis and accumulation of myeloid-derived suppressor cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Immunol. 2013 Feb 1;190(3):1372-9. doi: 10.4049/jimmunol.1201151. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 4049/jimmunol.1201151

AUTORES / AUTHORS:  - Vernon PJ; Loux TJ; Schapiro NE; Kang R; Muthuswamy R; Kalinski P; Tang D; Lotze MT; Zeh HJ 3rd

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDA) has an aggressive natural history and is resistant to therapy. The receptor for advanced glycation end products (RAGE) is  a pattern recognition receptor for many damage-associated molecular pattern molecules. RAGE is overexpressed in both human and murine models of PDA as well as most advanced epithelial neoplasms. The immunosuppressive nature of the PDA microenvironment is facilitated, in part, by the accumulation of regulatory immune cell infiltrates such as myeloid-derived suppressor cells (MDSCs). To study the role of RAGE expression in the setting of mutant Ras-promoted pancreatic carcinogenesis (KC), a triple-transgenic model of spontaneous murine PDA in a RAGE-null background (KCR) was generated. KCR mice had markedly delayed  pancreatic carcinogenesis and a significant diminution of MDSCs compared with KC  mice at comparable time points postweaning. Although RAGE was not required for the development or suppressor activity of MDSCs, its absence was associated with  temporally limited pancreatic neoplasia and altered phenotype and function of the myeloid cells. In lieu of MDSCs, KCR animals at comparable time points exhibited  mature CD11b(+)Gr1(-)F4/80(+) cells that were not immunosuppressive in vitro. KCR mice also maintained a significantly less suppressive milieu evidenced by marked  decreases in CCL22 in relation to CXCL10 and diminished serum levels of IL-6.

 

----------------------------------------------------

[24]

TÍTULO / TITLE:  - Risk of Cancer in Patients With Autoimmune Pancreatitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Gastroenterol. 2013 Jan 15. doi: 10.1038/ajg.2012.465.

            ●● Enlace al texto completo (gratuito o de pago) 1038/ajg.2012.465

AUTORES / AUTHORS:  - Shiokawa M; Kodama Y; Yoshimura K; Kawanami C; Mimura J; Yamashita Y; Asada M; Kikuyama M; Okabe Y; Inokuma T; Ohana M; Kokuryu H; Takeda K; Tsuji Y; Minami R; Sakuma Y; Kuriyama K; Ota Y; Tanabe W; Maruno T; Kurita A; Sawai Y; Uza N; Watanabe T; Haga H; Chiba T

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

RESUMEN / SUMMARY:  - OBJECTIVES:Although simultaneous occurrences of autoimmune pancreatitis (AIP) and cancer are occasionally observed, it remains largely unknown whether cancer and AIP occur independently or these disorders are interrelated. The aim of this study was to examine the relationship between AIP and cancer.METHODS:We conducted a multicenter, retrospective cohort study. One hundred and eight patients who met the Asian diagnostic criteria for AIP were included in the study. We calculated the proportion, standardized incidence ratio (SIR), relative risk, and time course of cancer development in patients with AIP. We also analyzed the clinicopathological characteristics of AIP patients with cancer in comparison with those without cancer.RESULTS:Of the 108 AIP patients, 18 cancers were found  in 15 patients (13.9%) during the median follow-up period of 3.3 years. The SIR of cancer was 2.7 (95% confidence interval (CI) 1.4-3.9), which was stratified into the first year (6.1 (95% CI 2.3-9.9)) and subsequent years (1.5 (95% CI 0.3-2.8)) after AIP diagnosis. Relative risk of cancer among AIP patients at the  time of AIP diagnosis was 4.9 (95% CI 1.7-14.9). In six of eight patients whose cancer lesions could be assessed before corticosteroid therapy for AIP, abundant  IgG4-positive plasma cell infiltration was observed in the cancer stroma. These six patients experienced no AIP relapse after successful cancer treatment.CONCLUSIONS:Patients with AIP are at high risk of having various cancers. The highest risk for cancer in the first year after AIP diagnosis and absence of AIP relapse after successful treatment of the coexisting cancers suggest that AIP may develop as a paraneoplastic syndrome in some patients.Am J Gastroenterol advance online publication, 15 January 2013; doi:10.1038/ajg.2012.465.

 

----------------------------------------------------

[25]

TÍTULO / TITLE:  - Pirfenidone Inhibits Pancreatic Cancer Desmoplasia by Regulating Stellate Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3180

AUTORES / AUTHORS:  - Kozono S; Ohuchida K; Eguchi D; Ikenaga N; Fujiwara K; Cui L; Mizumoto K; Tanaka M

INSTITUCIÓN / INSTITUTION:  - Departments of Surgery and Oncology, Kyushu University.

RESUMEN / SUMMARY:  - Pancreatic stellate cells (PSCs), which are implicated in desmoplasia in pancreatic cancer, enhance the malignancy of cancer cells and confer resistance to established treatments. We investigated whether the antifibrotic agent pirfenidone can suppress desmoplasia and exert anti-tumor effects against pancreatic cancer. Primary PSCs were established from pancreatic cancer tissue obtained during surgery. In vitro, pirfenidone inhibited the proliferation, invasiveness, and migration of PSCs in a dose-dependent manner. Although supernatants of untreated PSCs increased the proliferation, invasiveness, and migration of pancreatic cancer cells (PCCs), supernatants of pirfenidone-treated  PSCs decreased these effects. Exposure to PCC supernatant increased the production of platelet-derived growth factor-A, hepatic growth factor, collagen type I, fibronectin, and periostin in PSCs, which was significantly reduced by pirfenidone. Mice were subcutaneously implanted with PCCs (SUIT-2 cells) and PSCs into the right flank and PCCs alone into the left flank. Oral administration of pirfenidone to these mice significantly reduced tumor growth of co-implanted PCCs and PSCs, but not of PCCs alone. Pirfenidone also decreased the proliferation of  PSCs and the deposition of collagen type I and periostin in tumors. In mice with  orthotopic tumors consisting of PCCs co-implanted with PSCs, pirfenidone suppressed tumor growth, reduced the number of peritoneal disseminated nodules, and reduced the incidence of liver metastasis. Pirfenidone in combination with gemcitabine more effectively suppressed orthotopic tumor growth compared with pirfenidone or gemcitabine alone. In conclusion, our findings indicate that pirfenidone is a promising antitumor agent for pancreatic cancer, owing to its suppression of desmoplasia through regulating PSCs.

 

----------------------------------------------------

[26]

TÍTULO / TITLE:  - Loss of phosphatase and tensin homolog expression is associated with recurrence and poor prognosis in patients with pancreatic ductal adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hum Pathol. 2012 Dec 19. pii: S0046-8177(12)00329-2. doi: 10.1016/j.humpath.2012.09.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.09.001

AUTORES / AUTHORS:  - Foo WC; Rashid A; Wang H; Katz MH; Lee JE; Pisters PW; Wolff RA; Abbruzzese JL; Fleming JB; Wang H

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

RESUMEN / SUMMARY:  - Phosphatase and tensin homolog (PTEN) is a tumor suppressor in the AKT/mTOR pathway. Animal model studies have shown that loss of PTEN function is involved in the progression of pancreatic cancer. However, the prognostic significance of  loss of PTEN expression in pancreatic cancer is unclear. PTEN expression was evaluated by immunohistochemistry on tissue microarrays consisting of multiple cores of 133 resected stage II pancreatic ductal adenocarcinomas. A PTEN expression score was calculated as the product of the percentage of positive tumor cells and the intensity of PTEN staining. We categorized PTEN expression for each tumor as retained (PTEN score >5) or lost (PTEN score </=5). Thirty-four (25.6%) patients had tumors with loss of PTEN expression, and 99 (74.4%) had tumors with retained PTEN expression. Recurrence/Metastasis was observed in 88.2% (30/34) of patients whose tumors showed loss of PTEN compared with 68.7% (68/99)  of patients whose tumors showed retained PTEN (P = .03). Patients whose tumors showed loss of PTEN had a shorter overall survival (median, 19.9 +/- 3.6 months)  than did patients whose tumors had retained PTEN (32.7 +/- 5.0 months, P = .03).  In a multivariate analysis, loss of PTEN expression was an independent prognostic factor for poor overall survival in patients with stage II pancreatic ductal adenocarcinoma. No significant correlations between loss of PTEN expression and other clinicopathologic parameters were observed (P > .05). Assessment of PTEN expression may be used as a prognostic marker for patients with resected pancreatic ductal adenocarcinoma.

 

----------------------------------------------------

[27]

TÍTULO / TITLE:  - Phosphorylation of ribosomal protein S6 attenuates DNA damage and tumor suppression during development of pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2014

AUTORES / AUTHORS:  - Khalaileh A; Dreazen A; Kahtib A; Apel R; Swisa A; Kidess-Bassir N; Maitra A; Meyuhas O; Dor Y; Zamir G

INSTITUCIÓN / INSTITUTION:  - Developmental Biology and Cancer Research, Hebrew University Medical School.

RESUMEN / SUMMARY:  - The signaling pathways that mediate the development of pancreatic ductal adenocarcinoma (PDAC) downstream of mutant Kras remain incompletely understood. Here we focus on ribosomal protein S6 (rpS6), an mTOR effector not implicated previously in cancer. Phosphorylation of rpS6 was increased in pancreatic acinar  cells upon implantation of the chemical carcinogen dimethylbenzanthracene (DMBA)  or transgenic expression of mutant Kras. To examine the functional significance of rpS6 phosphorylation, we utilized knockin mice lacking all five phosphorylatable sites in rpS6 (termed rpS6P-/- mice). Strikingly, the development of pancreatic cancer precursor lesions induced by either DMBA or mutant Kras was greatly reduced in rpS6P-/- mice. rpS6 mutants expressing oncogenic Kras showed increased p53 along with increased staining of gamma-H2AX and 53bp1 (Trp53bp1) in areas of acinar-ductal metaplasia, suggesting that rpS6 phosphorylation attenuates Kras-induced DNA damage and p53-mediated tumor suppression. These results reveal that rpS6 phosphorylation is important for the  initiation of pancreatic cancer.

 

----------------------------------------------------

[28]

TÍTULO / TITLE:  - Hypomethylating therapy in an aggressive stroma-rich model of pancreatic carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 15;73(2):885-96. doi: 10.1158/0008-5472.CAN-12-1880. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-1880

AUTORES / AUTHORS:  - Shakya R; Gonda T; Quante M; Salas M; Kim S; Brooks J; Hirsch S; Davies J; Cullo A; Olive K; Wang TC; Szabolcs M; Tycko B; Ludwig T

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Institute for Cancer Genetics; Division of Digestive and Liver Diseases, Department of Medicine; and Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that resists current treatments. To test epigenetic therapy against this cancer, we used the DNA demethylating drug 5-aza-2’-deoxycytidine (DAC) in an aggressive mouse model  of stromal rich PDAC (KPC-Brca1 mice). In untreated tumors, we found globally decreased 5-methyl-cytosine (5-mC) in malignant epithelial cells and in cancer-associated myofibroblasts (CAF), along with increased amounts of 5-hydroxymethyl-cytosine (5-HmC) in CAFs, in progression from pancreatic intraepithelial neoplasia to PDAC. DAC further reduced DNA methylation and slowed PDAC progression, markedly extending survival in an early-treatment protocol and  significantly though transiently inhibiting tumor growth when initiated later, without adverse side effects. Escaping tumors contained areas of sarcomatoid transformation with disappearance of CAFs. Mixing-allografting experiments and proliferation indices showed that DAC efficacy was due to inhibition of both the  malignant epithelial cells and the CAFs. Expression profiling and immunohistochemistry highlighted DAC induction of STAT1 in the tumors, and DAC plus IFN-gamma produced an additive antiproliferative effect on PDAC cells. DAC induced strong expression of the testis antigen deleted in azoospermia-like (DAZL) in CAFs. These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy. Cancer Res; 73(2); 885-96. ©2012 AACR.

 

----------------------------------------------------

[29]

TÍTULO / TITLE:  - Therapeutic efficacy of bifunctional siRNA combining TGF-beta1 silencing with RIG-I activation in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 21.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-11-3850

AUTORES / AUTHORS:  - Ellermeier J; Wei J; Duewell P; Hoves S; Stieg MR; Adunka T; Noerenberg D; Anders HJ; Mayr D; Poeck H; Hartmann G; Endres S; Schnurr MM

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, University of Munich.

RESUMEN / SUMMARY:  - Deregulated transforming growth factor-beta (TGF-beta) signaling in pancreatic cancer promotes tumor growth, invasion, metastasis, and a potent immunosuppressive network. A strategy for disrupting this tumor-promoting pathway is silencing TGF-beta by small interfering RNA (siRNA). By introducing a triphosphate group at the 5’ end of siRNA (ppp-siRNA) gene silencing can be combined with immune activation via the cytosolic helicase retinoic acid-inducible gene I (RIG-I), a ubiquitously expressed receptor recognizing viral RNA. We validated RIG-I as a therapeutic target by showing that activation  of RIG-I in pancreatic carcinoma cells induced IRF-3 phosphorylation, production  of type I interferon (IFN), the chemokine CXCL10, as well as caspase-9 mediated tumor cell apoptosis. Next, we generated a bifunctional ppp-siRNA that combines RIG-I activation with gene silencing of TGF-beta1 (ppp-TGF-beta) and studied its  therapeutic efficacy the orthotopic Panc02 mouse model of pancreatic cancer. Intravenous injection of ppp-TGF-beta reduced systemic and tumor-associated TGF-beta levels. In addition, it induced high levels of type I IFN and CXCL10 in  serum and tumor tissue, systemic immune cell activation and profound tumor cell apoptosis in vivo. Treatment of mice with established tumors with ppp-TGF-beta significantly prolonged survival, as compared to ppp-RNA or TGF-beta siRNA alone. Furthermore, we observed the recruitment of activated CD8+ T cells to the tumor and a reduced frequency of CD11b+ Gr-1+ myeloid cells. Therapeutic efficacy was dependent on CD8+ T cells whereas NK cells were dispensable. In conclusion, combing TGF-beta gene silencing with RIG-I signaling confers potent anti-tumor efficacy against pancreatic cancer by braking tumor-induced CD8+ T cell suppression.

 

----------------------------------------------------

[30]

TÍTULO / TITLE:  - A Rare Pancreatic Tumor in a 52-Year-Old Chinese Woman.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastroenterology. 2013 Jan 17. pii: S0016-5085(12)01507-7. doi: 10.1053/j.gastro.2012.10.016.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.gastro.2012.10.016

AUTORES / AUTHORS:  - Jiang CY; Wang W; Yuan ZR

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Huadong Hospital, Fudan University, Shanghai, PR China.

 

----------------------------------------------------

[31]

TÍTULO / TITLE:  - Low expression of nucleus accumbens-associated protein 1 predicts poor prognosis  for patients with pancreatic ductal adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pathol Int. 2012 Dec;62(12):802-10. doi: 10.1111/pin.12020.

            ●● Enlace al texto completo (gratuito o de pago) 1111/pin.12020

AUTORES / AUTHORS:  - Nishi T; Maruyama R; Urano T; Nakayama N; Kawabata Y; Yano S; Yoshida M; Nakayama K; Miyazaki K; Takenaga K; Tanaka T; Tajima Y

INSTITUCIÓN / INSTITUTION:  - Department of Digestive and General Surgery, Shimane University Faculty of Medicine, Izumo, Japan.

RESUMEN / SUMMARY:  - Nucleus accumbens-associated protein 1 (NAC1) is overexpressed in various carcinomas including ovarian, cervical, breast, and pancreatic carcinomas. High expression of NAC1 is considered to have adverse effects on prognosis through negative regulation of growth arrest and DNA-damage-inducible 45-gamma interacting protein 1 (GADD45GIP1) in ovarian and cervical carcinomas. In the present study, the expression of NAC1 in pancreatic ductal adenocarcinoma (PDA) was measured using immunohistochemistry and computer-assisted image analysis in order to investigate its correlation with various clinicopathological parameters  and prognosis. Patients with low-NAC1 PDA had worse overall survival (P = 0.0010) and a shorter disease-free survival (P = 0.0036) than patients with high-NAC1 PDA. This was a clinical effect opposite to that reported in ovarian and cervical carcinomas. Furthermore, knockdown of NAC1 in pancreatic carcinoma cell lines did not increase expression of the GADD45GIP1 protein. These results indicate that the gene(s) regulated by NAC1 vary depending on the types of carcinoma or originating tissue, and that low expression of NAC1 predicts poor prognosis for patients with PDA.

 

----------------------------------------------------

[32]

TÍTULO / TITLE:  - Risk for Mortality From Causes Other Than Pancreatic Cancer in Patients With Intraductal Papillary Mucinous Neoplasm of the Pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318270ea97

AUTORES / AUTHORS:  - Kawakubo K; Tada M; Isayama H; Sasahira N; Nakai Y; Takahara N; Miyabayashi K; Yamamoto K; Mizuno S; Mohri D; Kogure H; Sasaki T; Yamamoto N; Tateishi R; Hirano K; Ijichi H; Tateishi K; Koike K

INSTITUCIÓN / INSTITUTION:  - From the Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

RESUMEN / SUMMARY:  - OBJECTIVES: The long-term prognosis in patients with intraductal papillary mucinous neoplasm (IPMN) has not been determined. The aim of this study was to elucidate the risk for nonpancreatic cancer-specific mortality in patients with IPMN. METHODS: Seven hundred ninety-three patients with IPMN who were followed up more than 1 year were included in this study. Fine and Gray competing risk regression was used to assess the risk for mortality unrelated to pancreatic cancer. A comorbidity score at diagnosis was assigned using the Adult Comorbidity Evaluation 27. RESULTS: After a median follow-up of 50 months, a high comorbidity score and age at diagnosis were significantly associated with a risk for mortality unrelated to pancreatic cancer. Adjusted hazards ratio and 95% confidence interval of each comorbidity burden were as follows: none, 1; mild, 2.68 (0.76-9.45; P = 0.124); moderate, 10.9 (3.19-37.1; P < 0.001); and severe, 32.0 (9.41-108.8; P < 0.001). Comorbidity burden did not affect the risk for pancreatic cancer-specific mortality. CONCLUSIONS: Comorbidity and age at diagnosis was significantly related to mortality unrelated to pancreatic cancer in patients with IPMN. For patients at high risk for nonpancreatic cancer mortality, a follow-up management may be more reasonable than surgery.

 

----------------------------------------------------

[33]

TÍTULO / TITLE:  - Inhibition of nuclear factor kappa-B enhances the antitumor effect of combination treatment with tumor necrosis factor-alpha gene therapy and gemcitabine for pancreatic cancer in mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Am Coll Surg. 2013 Feb;216(2):320-332.e3. doi: 10.1016/j.jamcollsurg.2012.09.016. Epub 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jamcollsurg.2012.09.016

AUTORES / AUTHORS:  - Fujiwara Y; Shiba H; Iwase R; Haruki K; Furukawa K; Uwagawa T; Misawa T; Ohashi T; Yanaga K

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan; Department of Gene Therapy, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: sheetan@jikei.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: Combination therapy with tumor necrosis factor-alpha (TNF-alpha) gene delivery and gemcitabine is a new therapeutic approach for pancreatic cancer. However, the efficacy of both TNF-alpha and gemcitabine is suppressed due to activation of nuclear factor-kappa B (NF-kappaB). We hypothesized that nafamostat mesilate (FUT175), an NF-kappaB inhibitor, enhances the antitumor effect of combination treatment with an adenoviral vector-expressing TNF-alpha (AxCAhTNF-alpha) and gemcitabine for pancreatic cancer in mice. STUDY DESIGN: In  vitro, we assessed that FUT175 inhibited both TNF-alpha- and gemcitabine-induced  NF-kappaB activation and enhanced apoptosis in human pancreatic cancer cell lines (MIAPaCa-2 and AsPC-1). In vivo, we established a xenograft pancreatic cancer model in mice by subcutaneous injection of MIAPaCa-2 and AsPC-1. The animals were treated with AxCAhTNF-alpha intratumorally and gemcitabine intraperitoneally once a week (combination group) or AxCAhTNF-alpha intratumorally and gemcitabine intraperitoneally once a week as well as FUT175 intraperitoneally 3 times a week  (triple combination group). RESULTS: In vitro, FUT175 inhibited both TNF-alpha- and gemcitabine-induced NF-kappaB activation and enhanced induction of apoptosis. In the triple combination group, tumor growth in vivo was significantly slower and there were more apoptotic cells than in the combination group (p < 0.05). CONCLUSIONS: Inhibition of NF-kappaB by FUT175 enhances the antitumor effect of combined TNF-alpha gene therapy and gemcitabine for pancreatic cancer.

 

----------------------------------------------------

[34]

TÍTULO / TITLE:  - Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT Within Patients with Gastroenteropancreatic Neuroendocrine Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Nucl Med. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 2967/jnumed.112.111724

AUTORES / AUTHORS:  - Wild D; Bomanji JB; Benkert P; Maecke H; Ell PJ; Reubi JC; Caplin ME

INSTITUCIÓN / INSTITUTION:  - Institute of Nuclear Medicine, University College Hospital, London, United Kingdom.

RESUMEN / SUMMARY:  - Somatostatin receptor PET tracers such as [(68)Ga-DOTA,1-Nal(3)]-octreotide ((68)Ga-DOTANOC) and [(68)Ga-DOTA,Tyr(3)]-octreotate ((68)Ga-DOTATATE) have shown promising results in patients with neuroendocrine tumors, with a higher lesion detection rate than is achieved with (18)F-fluorodihydroxyphenyl-l-alanine PET, somatostatin receptor SPECT, CT, or MR imaging. (68)Ga-DOTANOC has high affinity  for somatostatin receptor subtypes 2, 3, and 5 (sst(2,3,5)). It has a wider receptor binding profile than (68)Ga-DOTATATE, which is sst(2)-selective. The wider receptor binding profile might be advantageous for imaging because neuroendocrine tumors express different subtypes of somatostatin receptors. The goal of this study was to prospectively compare (68)Ga-DOTANOC and (68)Ga-DOTATATE PET/CT in the same patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and to evaluate the clinical impact of (68)Ga-DOTANOC PET/CT. METHODS: Eighteen patients with biopsy-proven GEP-NETs were evaluated with (68)Ga-DOTANOC and (68)Ga-DOTATATE using a randomized crossover design. Labeling of DOTANOC and DOTATATE with (68)Ga was standardized using a fully automated synthesis device. PET/CT findings were compared with 3-phase CT scans and in some patients with MR imaging, (18)F-FDG PET/CT, and histology. Uptake in organs and tumor lesions was quantified and compared by calculation of maximum standardized uptake values (SUVmax) using volume computer-assisted reading. RESULTS: Histology revealed low-grade GEP-NETs (G1) in 4 patients, intermediate grade (G2) in 7, and high grade (G3) in 7. (68)Ga-DOTANOC and (68)Ga-DOTATATE were false-negative in only 1 of 18 patients.  In total, 248 lesions were confirmed by cross-sectional and PET imaging. The lesion-based sensitivity of (68)Ga-DOTANOC PET was 93.5%, compared with 85.5% for (68)Ga-DOTATATE PET (P = 0.005). The better performance of (68)Ga-DOTANOC PET is  attributed mainly to the significantly higher detection rate of liver metastases  rather than tumor differentiation grade. Multivariate analysis revealed significantly higher SUVmax in G1 tumors than in G3 tumors (P = 0.009). This finding was less pronounced with (68)Ga-DOTANOC (P > 0.001). Altogether, (68)Ga-DOTANOC changed treatment in 3 of 18 patients (17%). CONCLUSION: The sst(2,3,5)-specific radiotracer (68)Ga-DOTANOC detected significantly more lesions than the sst(2)-specific radiotracer (68)Ga-DOTATATE in our patients with GEP-NETs. The clinical relevance of this finding has to be proven in larger studies.

 

----------------------------------------------------

[35]

TÍTULO / TITLE:  - Autoimmune Chronic Pancreatitis with IgG4-Related Pancreatic Pseudocyst in a Patient Undergoing Total Pancreatectomy Followed by Autologous Islet Transplantation: A Case Report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2013 Jan;42(1):175-177.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e3182546e37

AUTORES / AUTHORS:  - Takita M; Itoh T; Matsumoto S; Shimoda M; Chujo D; Iwahashi S; Tamura Y; Onaca N; Naziruddin B; Bartlett BL; Levy MF

INSTITUCIÓN / INSTITUTION:  - Islet Cell Laboratory Baylor Research Institute Dallas, TX Division of Cardiology Department of Internal Medicine Baylor University Medical Center Dallas, TX Baylor Institute for Immunology Research Dallas, TX Islet Cell Laboratory Baylor  Research Institute Dallas, TX The Annette C. and Harold C. Simmons Transplant Institute at Baylor University Medical Center Dallas, TX Department of Pathology  Baylor All Saints Medical Center Fort Worth, TX The Annette C. and Harold C. Simmons Transplant Institute at Baylor University Medical Center Dallas, TX marlonl@BaylorHealth.edu.

 

----------------------------------------------------

[36]

TÍTULO / TITLE:  - Gemcitabine and cisplatin combined with regional hyperthermia as second-line treatment in patients with gemcitabine-refractory advanced pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Hyperthermia. 2013;29(1):8-16. doi: 10.3109/02656736.2012.740764. Epub 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02656736.2012.740764

AUTORES / AUTHORS:  - Tschoep-Lechner KE; Milani V; Berger F; Dieterle N; Abdel-Rahman S; Salat C; Issels RD

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine III, Klinikum Grosshadern Medical Centre, Ludwig-Maximilians-University , Munich , Germany.

RESUMEN / SUMMARY:  - Purpose: There is no standard second-line therapy for patients with advanced pancreatic cancer (APC) after gemcitabine (G) failure. Cisplatin (Cis)-based chemotherapy has shown activity in APC. It is proven that cytotoxicity of G and Cis is enhanced by heat exposure at 40 degrees to 42 degrees C. Therefore G plus  Cis with regional hyperthermia (RHT) might be beneficial for patients with G-refractory APC. Patients and methods: We retrospectively analysed 23 patients with advanced (n = 2) or metastatic (n = 21) pancreatic cancer with relapse after G mono first-line chemotherapy (n = 23). Patients had received G (day 1, 1000 mg/m(2)) and Cis (day 2 and 4, 25 mg/m(2)) in combination with RHT (day 2 and 4,  1 h) biweekly for 4 months. We analysed feasibility, toxicity, time to second progression (TTP2), overall survival (OS) and clinical response. Results: Between October 1999 and August 2008 23 patients were treated. Haematological toxicity was low with no grade 4 event. Hyperthermia-associated toxicity consisted of discomfort because of bolus pressure (3%), power-related pain (7%) or position-related pain (17%). Median TTP1 was 5.9 months (95% confidence interval  (CI): 2.6-9.2), median TTP2 was 4.3 months (95%CI: 1.2-7.4) and OS 12.9 months (95%CI: 9.9-15.9). The disease control rate in 16 patients with available CT scans was 50%. Conclusion: We show first clinical data of G plus Cis with RHT being clinically active in G-pretreated APC with low toxicity. A prospective controlled phase II second-line clinical trial (EudraCT: 2005-003855-11) and a randomised phase III adjuvant clinical trial offering this treatment (HEAT; EudraCT: 2008-004802-14) are currently open for recruitment.

 

----------------------------------------------------

[37]

TÍTULO / TITLE:  - DNA Index as a Strong Prognostic Factor in Patients With Adenocarcinoma of the Pancreatic Head: Results of a 5-Year Prospective Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e3182773eb6

AUTORES / AUTHORS:  - Kamphues C; Al-Abadi H; Durr A; Al-Abadi N; Schricke D; Bova R; Muller V; Stenzinger A; Klauschen F; Seehofer D; Neuhaus P; Bahra M

INSTITUCIÓN / INSTITUTION:  - From the *Department of General, Visceral and Transplantation Surgery, Charite University Hospital, Berlin, Germany; daggerInstitute of Pathology, University Hospital, Heidelberg, Germany; and double daggerInstitute of Pathology, Charite University Hospital, Berlin, Germany.

RESUMEN / SUMMARY:  - OBJECTIVES: To improve the devastating prognosis of pancreatic cancer; the identification of reliable predictive factors is crucial. The aim of the present  study was to prospectively assess the prognostic value of DNA index determined by image cytometry as an predictive factor in pancreatic head cancer. METHODS: The DNA ploidy and the DNA index of 61 patients were evaluated by DNA image cytometry and were found to be correlated, as well as standard histopathologic parameters,  with patient survival. RESULTS: Through the DNA image cytometry, 15 tumors (24.6%) were identified as diploid and 46 (75.6%) as nondiploid. The median DNA index in the entire cohort was 1.9 (range, 1.0-2.5). Tumor stage, lymph node status, lymph node index, lymphatic invasion, and DNA index were identified as prognostic factors in the univariate analysis, but only DNA index (hazard ratio,  3.137; 95% confidence interval, 1.149-8.566; P = 0.026) and lymph node status (hazard ratio, 0.377; 95% confidence interval, 0.186-0.765; P = 0.007) were identified as independent predictive factors in the multivariate analysis. CONCLUSIONS: The DNA index represents an independent predictive marker in patients with pancreatic head cancer and a potential tool in designing specific treatment strategies for patients with pancreatic cancer.

 

----------------------------------------------------

[38]

TÍTULO / TITLE:  - Clinical utility of high-throughput glycome analysis in patients with pancreatic  cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastroenterol. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00535-012-0732-7

AUTORES / AUTHORS:  - Nouso K; Amano M; Ito YM; Miyahara K; Morimoto Y; Kato H; Tsutsumi K; Tomoda T; Yamamoto N; Nakamura S; Kobayashi S; Kuwaki K; Hagihara H; Onishi H; Miyake Y; Ikeda F; Shiraha H; Takaki A; Nakahara T; Nishimura SI; Yamamoto K

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8558, Japan, nouso@cc.okayama-u.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: Most of the glycan changes reported in cancers were based on the examinations of a small number of patients or particular proteins. The aim of this study was to determine the changes of the serum N-glycan profile comprehensively in a large number of pancreatic cancer patients and investigate its clinical utility. METHODS: Glycan levels in the serum of 92 pancreatic cancer patients and 243 healthy volunteers (HLT) were examined by comprehensive quantitative high-throughput glycome analysis and were compared with clinical parameters. RESULTS: Out of 66 glycans detected, 15 were differentially expressed in pancreatic cancer, and 10 out of the 15 glycans were significantly up-regulated in cases with distant metastasis. There was a clear increase in overall expression of serum glycans, especially highly-branched glycans with fucose moieties, in pancreatic cancer. Among these 15 glycans, a tri-antennary complex type glycan (m/z 3195) showed the highest area under the receiver operating characteristic curve (AUROC = 0.799) for the diagnosis of pancreatic cancer. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) was found to be significantly higher in pancreatic cancer than in HLT (median = 1.11 and 0.41, respectively; p < 0.0001, AUROC = 0.831). For this pair ratio, the hazard ratio for survival (2.60, 95 % CI = 1.44-4.79) was higher than that of any single glycan and 1-year survival of patients with a  high and low ratio was 36.9 and 69.2 %, respectively, (p = 0.001). CONCLUSIONS: Comprehensive glycome analysis can be used to know the presence of pancreatic cancer, distant metastasis, and patient prognosis, simultaneously.

 

----------------------------------------------------

[39]

TÍTULO / TITLE:  - Soluble receptor of advanced glycation end products (sRAGE) indicates response to chemotherapy in pancreatic cancer patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Pharmacol Ther. 2013 Jan;51(1):67-9.

AUTORES / AUTHORS:  - Wittwer C; Boeck S; Heinemann V; Haas M; Stieber P; Nagel D; Holdenrieder S

INSTITUCIÓN / INSTITUTION:  - University Hospital Munich, Institute of Clinical Chemistry, University Hospital  Munich, Department of Internal Medicine III and Comprehensive Cancer Center, Munich, and University Hospital Bonn, Institute of Clinical Chemistry and Clinical Pharmacology, Bonn, Germany.

 

----------------------------------------------------

[40]

TÍTULO / TITLE:  - Diagnostic accuracy of an “amended” insulin-glucose ratio for the biochemical diagnosis of insulinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Intern Med. 2012 Dec 4;157(11):767-75. doi: 10.7326/0003-4819-157-11-201212040-00004.

            ●● Enlace al texto completo (gratuito o de pago) 7326/0003-4819-157-11-201212040-00004

AUTORES / AUTHORS:  - Nauck MA; Meier JJ

INSTITUCIÓN / INSTITUTION:  - Diabeteszentrum Bad Lauterberg, Kirchberg 21, D-37431 Bad Lauterberg im Harz, Germany. nauck@diabeteszentrum.de

RESUMEN / SUMMARY:  - BACKGROUND: Recent biochemical diagnostic guidelines for insulinomas require demonstration of hypoglycemia with inappropriately elevated (nonsuppressed) insulin, C-peptide, or proinsulin, but these criteria may overlap with those in patients without insulinomas. Use of an “amended” insulin-glucose ratio that accounts for the normal variation in insulin secretion according to prevailing glycemia may improve diagnostic accuracy. OBJECTIVE: To compare the diagnostic accuracy of current diagnostic guideline criteria with the amended insulin-glucose ratio in patients with a suspected insulinoma. DESIGN: Retrospective cohort study. SETTING: 2 specialized university departments in Germany. PATIENTS: 114 patients with suspected hypoglycemia over 10 years having  diagnostic prolonged fasts. MEASUREMENTS: Glucose, insulin, C-peptide, and the amended insulin-glucose ratio were measured during and at discontinuation of prolonged fasts. RESULTS: Of 114 patients who were evaluated, 49 had surgical resection of histologically confirmed insulinomas. Insulinoma was excluded in 65  patients; follow-up for a mean of 10 years (range, 0 to 16 years) showed no progressively severe hypoglycemic events or diagnoses of insulinoma. Patients with insulinoma had lower glucose levels and higher insulin and C-peptide levels  overall than did control patients at the end of prolonged fasts, but there was considerable overlap. The amended insulin-glucose ratio correctly identified 48 of 49 patients with insulinoma and excluded the diagnosis in 64 of 65 control patients, resulting in positive and negative predictive values of 0.98 (95% CI, 0.89 to 1.00) and 0.99 (CI, 0.92 to 1.00), respectively, compared with 0.75 (CI,  0.63 to 0.85) and 0.98 (CI, 0.89 to 1.00), respectively, for glucose, insulin, and C-peptide concentration criteria. LIMITATION: The study had a retrospective design, no proinsulin concentrations were available, and a nonspecific insulin immunoassay (crossreactive with proinsulin) was used. CONCLUSION: The amended insulin-glucose ratio showed improved diagnostic accuracy over established criteria that use glucose, insulin, and C-peptide concentrations. PRIMARY FUNDING SOURCE: None.

 

----------------------------------------------------

[41]

TÍTULO / TITLE:  - Novel HIF2A mutations disrupt oxygen sensing leading to polycythemia, paragangliomas and somatostatinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Blood. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1182/blood-2012-10-460972

AUTORES / AUTHORS:  - Yang C; Sun MG; Matro J; Huynh TT; Rahimpour S; Prchal JT; Lechan R; Lonser R; Pacak K; Zhuang Z

INSTITUCIÓN / INSTITUTION:  - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States;

RESUMEN / SUMMARY:  - Hypoxia inducible factors (HIFs) control the cellular response to hypoxia and when dysregulated, contribute to tumorigenesis. Previously, we identified two gain-of-function somatic mutations in patients presenting with multiple paragangliomas or somatostatinomas, and polycythemia. Here we report two additional unique HIF2A mutations, which disrupt the hydroxylation domain recognized by prolyl hydroxylase domain-2 containing protein (PHD2), leading to stabilization of HIF-2alpha and increased expression of hypoxia-related genes.

 

----------------------------------------------------

[42]

TÍTULO / TITLE:  - Dosimetric Analysis of Organs at Risk During Expiratory Gating in Stereotactic Body Radiation Therapy for Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2012 Dec 27. pii: S0360-3016(12)03311-1. doi: 10.1016/j.ijrobp.2012.07.2366.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.07.2366

AUTORES / AUTHORS:  - Taniguchi CM; Murphy JD; Eclov N; Atwood TF; Kielar KN; Christman-Skieller C; Mok E; Xing L; Koong AC; Chang DT

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.

RESUMEN / SUMMARY:  - PURPOSE: To determine how the respiratory phase impacts dose to normal organs during stereotactic body radiation therapy (SBRT) for pancreatic cancer. METHODS  AND MATERIALS: Eighteen consecutive patients with locally advanced, unresectable  pancreatic adenocarcinoma treated with SBRT were included in this study. On the treatment planning 4-dimensional computed tomography (CT) scan, the planning target volume (PTV), defined as the gross tumor volume plus 3-mm margin, the duodenum, and the stomach were contoured on the end-expiration (CT(exp)) and end-inspiration (CT(insp)) phases for each patient. A separate treatment plan was constructed for both phases with the dose prescription of 33 Gy in 5 fractions with 95% coverage of the PTV by the 100% isodose line. The dose-volume histogram  (DVH) endpoints, volume of duodenum that received 20 Gy (V(20)), V(25), and V(30) and maximum dose to 5 cc of contoured organ (D(5cc)), D(1cc), and D(0.1cc), were  evaluated. RESULTS: Dosimetric parameters for the duodenum, including V(25), V(30), D(1cc), and D(0.1cc) improved by planning on the CT(exp) compared to those on the CT(insp). There was a statistically significant overlap of the PTV with the duodenum but not the stomach during the CT(insp) compared to the CT(exp) (0.38 +/- 0.17 cc vs 0.01 +/- 0.01 cc, P=.048). A larger expansion of the PTV, in accordance with a Danish phase 2 trial, showed even more overlapping volume of duodenum on the CT(insp) compared to that on the CT(exp) (5.5 +/- 0.9 cc vs 3.0 +/- 0.8 cc, P=.0003) but no statistical difference for any stomach dosimetric DVH parameter. CONCLUSIONS: Dose to the duodenum was higher when treating on the inspiratory than on the expiratory phase. These data suggest that expiratory gating may be preferable to inspiratory breath-hold and free breathing strategies for minimizing risk of toxicity.

 

----------------------------------------------------

[43]

TÍTULO / TITLE:  - Phase II study of sunitinib in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Invest New Drugs. 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10637-012-9910-y

AUTORES / AUTHORS:  - Ito T; Okusaka T; Nishida T; Yamao K; Igarashi H; Morizane C; Kondo S; Mizuno N; Hara K; Sawaki A; Hashigaki S; Kimura N; Murakami M; Ohki E; Chao RC; Imamura M

INSTITUCIÓN / INSTITUTION:  - Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, Japan, itopapa@intmed3.med.kyushu-u.ac.jp.

RESUMEN / SUMMARY:  - Background. Pancreatic neuroendocrine tumors (NETs) are rare but are frequently diagnosed at advanced stages and require systemic therapy. Patients and methods.  This multicenter, open-label, phase II study evaluated sunitinib in Japanese patients with well-differentiated pancreatic NET. Patients received sunitinib 37.5 mg/day on a continuous daily dosing (CDD) schedule. The primary endpoint was clinical benefit rate (CBR; percentage of complete responses [CRs] plus partial responses [PRs] plus stable disease [SD] >/=24 weeks). Secondary endpoints included objective response rate (ORR), tumor shrinkage, progression-free survival (PFS) probability, safety, pharmacokinetics, and biomarkers. Results. Twelve patients received treatment. The CBR was 75 % (95 % confidence interval [CI], 43-94) and included 6 patients with a PR and 3 with SD. The ORR was 50 % (95 % CI, 21-79). PFS probability was 91 % (95 % CI, 54-99) at 6 months and 71 %  (95 % CI, 34-90) at 12 months. Commonly reported treatment-emergent (all-causality), any-grade adverse events included diarrhea (n = 10), hand-foot syndrome and hypertension (both n = 8), fatigue and headache (both n = 7), and neutropenia (n = 6). No deaths on study were reported; one death due to disease progression occurred >28 days after end of treatment. Sunitinib on a CDD schedule resulted in sustained drug concentrations without accumulation across cycles. Tumor responses in all 12 patients did not appear to correlate with decreases in  chromogranin A levels. Conclusions. Sunitinib 37.5 mg/day on a CDD schedule demonstrated antitumor activity in Japanese patients with unresectable, well-differentiated pancreatic NET. Commonly reported adverse events were consistent with the known safety profile of sunitinib.

 

----------------------------------------------------

[44]

TÍTULO / TITLE:  - Low-dose gemcitabine depletes regulatory T cells and improves survival in the orthotopic Panc02 model of pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Cancer. 2012 Dec 12. doi: 10.1002/ijc.27990.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.27990

AUTORES / AUTHORS:  - Shevchenko I; Karakhanova S; Soltek S; Link J; Bayry J; Werner J; Umansky V; Bazhin AV

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, University of Heidelberg, Germany; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Heidelberg, Germany.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human neoplasms with extremely poor prognosis and a low survival rate. Immunosuppressive cell populations, e.g. regulatory T cells (Treg), appear to be  important in PDAC, contributing to patient’s poor prognosis. Therefore, we investigated the PDAC microenvironment with a focus on conventional and regulatory T cells in view of their potential therapeutic importance. We found that tumors from the murine Panc02 orthotopic model of PDAC were infiltrated with high numbers of Treg. Remarkably, these cells exhibited the effector/memory phenotype, suggesting their enhanced suppressive activity and higher proliferation capacity. Although we observed a steady increase in transforming growth factor-beta (TGF-beta) levels in the tumors, treatment with a specific inhibitor of TGF-beta receptor I kinase failed to abrogate Treg accumulation. A CCR4 antagonist did not affect Treg percentage in the tumor either. However, intense Treg cell division in the tumor microenvironment was demonstrated, suggesting local proliferation as a major mechanism of Treg accumulation in PDAC. Notably, this accumulation was reduced by low-dose gemcitabine administration, resulting in a modestly increased survival of PDAC mice. Our results provide an insight into mechanisms of immunosuppression in PDAC, suggesting an important role for proliferative expansion of effector/memory Treg. Low-dose gemcitabine therapy selectively depletes Treg, providing a basis for new modalities of PDAC therapy.

 

----------------------------------------------------

[45]

TÍTULO / TITLE:  - Tumor Size on Abdominal MRI Versus Pathologic Specimen in Resected Pancreatic Adenocarcinoma: Implications for Radiation Treatment Planning.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Jan 3. pii: S0360-3016(12)03816-3. doi: 10.1016/j.ijrobp.2012.11.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.11.019

AUTORES / AUTHORS:  - Hall WA; Mikell JL; Mittal P; Colbert L; Prabhu RS; Kooby DA; Nickleach D; Hanley K; Sarmiento JM; Ali AN; Landry JC

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Emory University, Atlanta, Georgia; Winship Cancer Institute, Emory University, Atlanta, Georgia. Electronic address: whall4@emory.edu.

RESUMEN / SUMMARY:  - PURPOSE: We assessed the accuracy of abdominal magnetic resonance imaging (MRI) for determining tumor size by comparing the preoperative contrast-enhanced T1-weighted gradient echo (3-dimensional [3D] volumetric interpolated breath-hold [VIBE]) MRI tumor size with pathologic specimen size. METHODS AND MATERIALS: The  records of 92 patients who had both preoperative contrast-enhanced 3D VIBE MRI images and detailed pathologic specimen measurements were available for review. Primary tumor size from the MRI was independently measured by a single diagnostic radiologist (P.M.) who was blinded to the pathology reports. Pathologic tumor measurements from gross specimens were obtained from the pathology reports. The maximum dimensions of tumor measured in any plane on the MRI and the gross specimen were compared. The median difference between the pathology sample and the MRI measurements was calculated. A paired t test was conducted to test for differences between the MRI and pathology measurements. The Pearson correlation coefficient was used to measure the association of disparity between the MRI and  pathology sizes with the pathology size. Disparities relative to pathology size were also examined and tested for significance using a 1-sample t test. RESULTS:  The median patient age was 64.5 years. The primary site was pancreatic head in 81 patients, body in 4, and tail in 7. Three patients were American Joint Commission on Cancer stage IA, 7 stage IB, 21 stage IIA, 58 stage IIB, and 3 stage III. The  3D VIBE MRI underestimated tumor size by a median difference of 4 mm (range, -34-22 mm). The median largest tumor dimensions on MRI and pathology specimen were 2.65 cm (range, 1.5-9.5 cm) and 3.2 cm (range, 1.3-10 cm), respectively. CONCLUSIONS: Contrast-enhanced 3D VIBE MRI underestimates tumor size by 4 mm when compared with pathologic specimen. Advanced abdominal MRI sequences warrant further investigation for radiation therapy planning in pancreatic adenocarcinoma before routine integration into the treatment planning process.

 

----------------------------------------------------

[46]

TÍTULO / TITLE:  - Show Us the Money: Role of Pancreatectomy and Vascular Reconstruction in Pancreatic Cancer in the Coming Era of Value-Based Payment Comment on “Concomitant Vascular Reconstruction During Pancreatectomy for Malignant Disease”

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Surg. 2012 Dec 17:1. doi: 10.1001/jamasurg.2013.1068.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jamasurg.2013.1068

AUTORES / AUTHORS:  - Ellison EC

 

----------------------------------------------------

[47]

TÍTULO / TITLE:  - Left-sided portal hypertension secondary to pancreatic cancer: clinical features, surgical treatment and outcome of 48 cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hepatogastroenterology. 2013 Jan 9;60(126). doi: 10.5754/hge12986.

            ●● Enlace al texto completo (gratuito o de pago) 5754/hge12986

AUTORES / AUTHORS:  - Yalin K; Hongyi Z; Xiaojun H; Chengli L; Mei X; Di W; Gang Z; Yuying Z

RESUMEN / SUMMARY:  - Background Features of LSPH secondary to pancreatic cancer is ambiguous, and controversy remains in the treatment. Methods 48 cases from our department were retrospectively analyzed to evaluate the clinical features, as well as the feasibility and effect of surgical treatment. Results 16 patients had gastrointestinal hemorrhage history. Laboratory findings showed normocytic and normochromic anemia, thrombocytopenia, lymphocyte reduction, and elevated liver enzyme. Tumor markers were normal in 12 patients. Ultrasonography showed splenic  venous obstruction in 40 patients and splenomegaly in 35. Esophagogastric varices could be detected by endoscopy in 40 patients and by CT in 37. Radical resection  was performed in 43 patients and splenectomy or additional devascularization in 29. 15 patients had gastrointestinal bleeding during follow-up, and the median survival time was 11.0 months. Conclusion Associated LSPH brought special features to pancreatic cancer. Radical resection, as well as splenectomy or additional devascularization for varices above Grade II, was worth performing.

 

----------------------------------------------------

[48]

TÍTULO / TITLE:  - Glucose and lipid metabolism in patients with advanced pancreatic cancer receiving palliative chemotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2013 Jan;33(1):287-92.

AUTORES / AUTHORS:  - Zeiss K; Parhofer KG; Heinemann V; Haas M; Laubender RP; Holdenrieder S; Schulz C; Boeck S

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, D-81377 Munich, Germany. stefan.boeck@med.uni-muenchen.de.

RESUMEN / SUMMARY:  - BACKGROUND: The role of diabetes mellitus (DM) in the pathogenesis of pancreatic  cancer (PC) and its prognostic role on patients with advanced disease remain undefined. PATIENTS AND METHODS: Within a prospective single-center pilot study,  30 consecutive patients with advanced PC underwent metabolic profiling for glucose (fasting glucose level, oral glucose tolerance test (oGTT), serum insulin levels) and lipid metabolism (cholesterol, triglycerides, lipoprotein a) at the initiation of and two months after chemotherapy. Subgroups (DM vs. non-DM) were analyzed with regard to metabolic and outcome parameters. RESULTS: Sixteen patients (53%) had DM, in seven of whom DM was newly-diagnosed by an oGTT. Patients in the DM subgroup had a higher prevalence of hypertension (p=0.05) and  a higher BMI (p=0.01), but with no significant differences in pre-treatment cholesterol (p=0.55) and triglyceride levels (p=0.37). Regarding baseline oncological parameters, patients with DM more often had a reduced performance status (p=0.06), and were more likely to present with metastatic disease (p=0.09). The median overall survival was 3.9 months in the DM group and 8.3 months in the non-DM group (hazard ratio=0.67, 95% confidence interval=0.31-1.45, p=0.31), respectively. CONCLUSION: The incidence of DM is high in patients with PC and the lipid profile associated with DM may be different from that of patients with metabolic syndromes. The role of DM as a negative prognostic factor in advanced PC remains to be determined.

 

----------------------------------------------------

[49]

TÍTULO / TITLE:  - Organic Anion Transporting Polypeptides Expressed in Pancreatic Cancer May Serve  As Potential Diagnostic Markers and Therapeutic Targets for Early Stage Adenocarcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pharm Res. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11095-012-0962-7

AUTORES / AUTHORS:  - Hays A; Apte U; Hagenbuch B

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, Kansas, 66160, USA.

RESUMEN / SUMMARY:  - PURPOSE: Organic Anion Transporting Polypeptides (OATPs) are expressed in various epithelial tissues in the body. Because they can be expressed in cancers and because they can transport anticancer drugs, OATPs could be potential targets for cancer therapy. Therefore we examined their expression in human pancreatic ductal adenocarcinomas. METHODS: Expression of all 11 human OATPs was measured at the mRNA level and OATPs with highest expression were characterized at the protein level. RESULTS: Transcripts of SLCO1B3, SLCO2A1, SLCO3A1 and SLCO4A1 were detected in all the tested pancreatic tissues. OATP1B3, OATP2A1, OATP3A1 and OATP4A1 protein expression was confirmed in these tissues and expression of all four transporters increased in pancreatic adenocarcinoma compared to normal pancreas. OATP1B3 expression was highest in pancreatic hyperplasia and stage one  adenocarcinomas compared to stage two and three adenocarcinomas. CONCLUSION: OATP1B3, OATP2A1, OATP3A1 and OATP4A1 are up-regulated in pancreatic adenocarcinoma and could potentially be used to target anticancer drugs to pancreatic cancer. Additionally, because expression of OATP1B3 is highest in pancreatitis and stage one adenocarcinoma, which leads to pancreatic cancer, OATP1B3 is a potential marker to diagnose patients with early stage pancreatic adenocarcinomas.

 

----------------------------------------------------

[50]

TÍTULO / TITLE:  - Adjuvant Pharmacotherapy in the Management of Elderly Patients with Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Drugs Aging. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s40266-013-0049-0

AUTORES / AUTHORS:  - Marechal R; Demols A; Van Laethem JL

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, GI Cancer Unit, Erasme University Hospital, Universite Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium, raphael.marechal@erasme.ulb.ac.be.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is the fourth or fifth leading cause of death from cancer in Western industrialized countries. Surgical resection is the  only chance of cure, but only 15-20 % of cases are potentially resectable at presentation, and despite complete resection, the overall prognosis remains relatively poor. Adjuvant therapy has modestly improved cure rates. The majority  of patients with pancreatic cancer are over the age of 65 years. But this age group is underrepresented within clinical trials, and it is unknown whether older patients achieve similar results to younger ones in terms of survival and treatment tolerance. In addition, there are no clinical trials dedicated to the elderly. Retrospective studies coming from the non-resectable setting provide some understanding on outcomes in older patients with PDAC. To date, we can reasonably argue that selected elderly patients with PDAC can benefit from curative surgery and postoperative chemotherapy as do their younger counterparts, without a significant increase in morbidity and mortality. Gemcitabine should be  preferred to 5-fluorouracil on the basis of a better risk-benefit balance.

 

----------------------------------------------------

[51]

TÍTULO / TITLE:  - Deciphering the Mechanisms of Tumorigenesis in Human Pancreatic Ductal Epithelial Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-0032

AUTORES / AUTHORS:  - Chang Z; Li Z; Wang X; Kang Y; Yuan Y; Niu J; Wang H; Chatterjee D; Fleming JB; Li M; Abbruzzese JL; Chiao PJ

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Molecular and Cellular Oncology, Surgical Oncology, and Pathology, Breast Medical Oncology, and Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center; The Cancer Biology Program of The University of Texas Graduate School of Biomedical Sciences at Houston; The Vivian L. Smith Department of Neurosurgery, Department of Integrative Biology and Pharmacology, The University of Texas Medical School at Houston, Houston, Texas; Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.

RESUMEN / SUMMARY:  - PURPOSE: The most common genetic lesions in pancreatic ductal adenocarcinoma (PDAC) have been identified. However, significant gaps still exist in our understanding of how such genetic alterations act in concert to induce PDAC development. In this study, we investigated the mechanism of tumorigenic transformation in the immortalized human pancreatic ductal epithelial (HPDE) cell line by sequentially introducing PDAC signature alterations into this cell line.EXPERIMENTAL DESIGN: The phenotype for stable expression of mutant K-ras, Her2, p16/p14shRNA, and Smad4shRNA in HPDE cells was examined by assays for cell  proliferation, migration, invasion, soft agar, and orthotopic tumorigenesis. The  mechanisms of tumorigenic transformation were further explored by gene expression profiling and pathway analyses.RESULTS: The transformed cells exhibited enhanced  proliferation, migration, and invasion, displayed anchorage-independent growth in soft agar, and grew orthotopic tumors with some histopathologic features of PDAC. We found that Smad4 played key roles in the tumorigenic transformation of HPDE cells. We further found that MDM2 and Bmi-1 were overexpressed in the tumorigenic HPDE cells and that Bmi-1 overexpression was regulated by Smad4. Ingenuity Pathway Analysis software analysis of microarray data revealed that dysregulation of integrin-linked kinase signaling and the cell cycle were the most significant  changes involved in tumorigenic transformation. Altogether, this cell culture model closely recapitulated human pancreatic carcinogenesis from gene lesions, activation of specific signaling pathways, and some histopathologic features.CONCLUSION: The combination of activated K-ras and Her2 with inactivated p16/p14 and Smad4 was sufficient and essential to transform HPDE cells, thus revealing the potential tumorigenic mechanism. Clin Cancer Res; 19(3); 1-11. ©2012 AACR.

 

----------------------------------------------------

[52]

TÍTULO / TITLE:  - Alleviating visceral cancer pain in patients with pancreatic cancer using cryoablation and celiac plexus block.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cryobiology. 2012 Dec 23. pii: S0011-2240(12)00272-6. doi: 10.1016/j.cryobiol.2012.12.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cryobiol.2012.12.002

AUTORES / AUTHORS:  - Niu L; Wang Y; Yao F; Wei C; Chen Y; Zhang L; Chen J; Li J; Zuo J; Xu K

INSTITUCIÓN / INSTITUTION:  - Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, Guangdong,  China; Fuda Institute of Cryosurgery for Cancer, Guangzhou, Guangdong, China.

RESUMEN / SUMMARY:  - Little is known about the effects of pancreas cryoablation (PCA) on abdominalgia  in pancreatic cancer patients or its synergism with celiac plexus block (CPB). In patients without abdominalgia, to investigate the effects of PCA; in patients with abdominalgia, to investigate the pain-alleviating effects of PCA+CPB. Sixty-two patients were enrolled in this retrospective review; 12 without abdominalgia refused PCA, 15 without abdominalgia received PCA to reduce their tumor load and 35 with abdominalgia received PCA+CPB to reduce tumor load and alleviate pain. All PCA and PCA+CPB procedures were performed successfully. Some  slight adverse effects (e.g. increased serum amylase, abdominal distension and nausea, abdominal bleeding) had disappeared by 3weeks, spontaneously or after symptomatic treatment. In patients without abdominalgia, pain occurred in one-third of cases (all with pancreatic head cancer) after PCA but had stopped 1-12days after treatment; in patients with abdominalgia before treatment, pain stopped immediately after PCA+CPB in 18 cases and 2-24days after treatment in 17  (all with pancreatic head cancer); a significant difference was found between pretreatment and post-treatment pain frequency (P=0.0019), regardless of the presence of advanced (P=0.0096) or metastatic (P=0.0072) cancer. The average time to pain relief was approximately 7days after both PCA and PCA+CPB, and abdominalgia did not recur for more than 8weeks. PCA may cause short-term pain in some pancreatic cancer patients. Combined PCA+CPB can alleviate cancer pain for more than 8weeks, without severe side effects.

 

----------------------------------------------------

[53]

TÍTULO / TITLE:  - CA19-9 as a Predictor of Resectability in Patients with Borderline Resectable Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hepatogastroenterology. 2013 Jan 16;60(126). doi: 10.5754/hge12921.

            ●● Enlace al texto completo (gratuito o de pago) 5754/hge12921

AUTORES / AUTHORS:  - He Z; Lu H; Du X; Hu W; Zhaoda BT

RESUMEN / SUMMARY:  - Background/Aims: The aim of the present study was to evaluate whether CA19-9 level related to the curative resection and prevented unnecessary laparotomy in patients with borderline resectable pancreatic cancer. Methodology: Retrospectively, logistic multivariate regression analysis was used to analyze data from 207 patients who underwent laparotomy for planned surgical resection at West China Hospital, during a 5-year period, and performed to identify CA19-9 levels contributing significantly to surgical resection. Inoperable patients were excluded. Results: Patients with CA19-9 >150U/mL had a frequency of surgical resection 11.7% (14/120) vs. 34.5% (30/87) in those patients with a lower level of CA19-9 (p<0.001). Patients with larger tumor size had a 1.98-fold increased risk of unresectability compared to those with smaller tumor size (p=0.046). Using multivariate analysis adjusted the effects of other factors, high level of  CA19-9 and larger tumor size were both considered to be an important risk factor  for influencing surgical resection. Conclusions: CA19-9 should be a good predictor of surgical resection possibility in patients with borderline resectable pancreatic cancer. Furthermore, it is useful in prognosis and optimizing surgical strategy.

 

----------------------------------------------------

[54]

TÍTULO / TITLE:  - Collagen triple helix repeat containing-1 promotes pancreatic cancer progression  by regulating migration and adhesion of tumor cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgs378

AUTORES / AUTHORS:  - Park EH; Kim S; Jo JY; Kim SJ; Hwang Y; Kim JM; Song SY; Lee DK; Koh SS

INSTITUCIÓN / INSTITUTION:  - Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.

RESUMEN / SUMMARY:  - Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein involved in vascular remodeling, bone formation and developmental morphogenesis. CTHRC1 has recently been shown to be expressed in human cancers such as breast cancer and melanoma. In this study, we show that CTHRC1 is highly expressed in human pancreatic cancer tissues and plays a role in the progression and metastasis of the disease. CTHRC1 promoted primary tumor growth and metastatic spread of cancer cells to distant organs in orthotopic xenograft tumor mouse models. Overexpression of CTHRC1 in cancer cells resulted in increased motility and adhesiveness, whereas these cellular activities were diminished by down-regulation of the protein. CTHRC1 activated several key signaling molecules, including Src, focal adhesion kinase, paxillin, mitogen-activated protein kinase  kinase (MEK), extracellular signal-regulated kinase and Rac1. Treatment with chemical inhibitors of Src, MEK or Rac1 and expression of dominant-negative Rac1  attenuated CTHRC1-induced cell migration and adhesion. Collectively, our results  suggest that CTHRC1 has a role in pancreatic cancer progression and metastasis by regulating migration and adhesion activities of cancer cells.

 

----------------------------------------------------

[55]

TÍTULO / TITLE:  - Methylation-mediated silencing of the miR-124 genes facilitates pancreatic cancer progression and metastasis by targeting Rac1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncogene. 2013 Jan 21. doi: 10.1038/onc.2012.598.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2012.598

AUTORES / AUTHORS:  - Wang P; Chen L; Zhang J; Chen H; Fan J; Wang K; Luo J; Chen Z; Meng Z; Liu L

INSTITUCIÓN / INSTITUTION:  - 1] Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

RESUMEN / SUMMARY:  - Previous studies have demonstrated that microRNA (miRNA) expression is altered in human cancer. However, the molecular mechanism underlying these changes in miRNA  expression remains unclear. In this study, we investigated the epigenetic modification of miR-124 genes and the potential function of miR-124 in pancreatic cancer. Using pyrosequencing analysis, we found that miR-124 genes (including miR-124-1, miR-124-2 and miR-124-3) are highly methylated in pancreatic cancer tissues compared with in non-cancerous tissues. Hypermethylation mediated the silencing of miR-124, which was a frequent event in pancreatic duct adenocarcinoma (PDAC). Furthermore, miR-124 downregulation was significantly associated with worse survival of PDAC patients. Functional studies showed that miR-124 inhibited cell proliferation, invasion and metastasis. Furthermore, we characterized Rac1 as a direct target of miR-124, and miR-124 interacted with the 3’-untranslated region of Rac1, which we showed to be a putative tumor promoter in pancreatic cancer. Thus, the miR-124-mediated downregulation of Rac1 led to the inactivation of the MKK4-JNK-c-Jun pathway. Therefore, our study demonstrates that miR-124 is a tumor suppressor miRNA that is epigenetically silenced in pancreatic cancer. Our findings suggest a previously unidentified molecular mechanism involved in the progression and metastasis of pancreatic cancer.Oncogene advance online publication, 21 January 2013; doi:10.1038/onc.2012.598.

 

----------------------------------------------------

[56]

TÍTULO / TITLE:  - Tspan8, CD44v6 and alpha6beta4 are biomarkers of migrating pancreatic cancer initiating cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Cancer. 2013 Jan 22. doi: 10.1002/ijc.28044.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28044

AUTORES / AUTHORS:  - Wang H; Rana S; Giese N; Buchler MW; Zoller M

INSTITUCIÓN / INSTITUTION:  - Department of Tumor Cell Biology, University Hospital of Surgery, Heidelberg, Germany.

RESUMEN / SUMMARY:  - Pancreatic adenocarcinoma (PaCa) being the deadliest cancer is partly due to early metastatic spread. Thus, we searched for PaCa initiating cell (PaCIC) markers with emphasis on markers contributing to metastatic progression. PaCIC were enriched from long-term and freshly-established lines by repeated selection  for spheroid or holoclone growth in advance of evaluating PaCIC markers. Sphere and holoclone formation steeply increased by re-cloning and remained stable thereafter. Cells not forming spheres or holoclones died upon re-cloning. PaCIC enrichment in spheres and holoclones was accompanied by increased motility, anchorage-independence and up-regulated CXCR4 expression. After subcutaneous injection in NOD/SCID mice tumorigenicity and, impressively, recovery of metastasizing tumor cells in peripheral blood, spleen, bone marrow, lung and pancreas was strongly increased in spheres and holoclones. PaCIC-enrichment in spheres and holoclones was accompanied, besides CXCR4, by up-regulated CD44v6, alpha6beta4, weakly CD133 and tetraspanin Tspan8 expression. Notably, CD44v6, alpha6beta4, CXCR4 and Tspan8 expressing PaCa cells had a growth advantage in vivo and became dominating in migrating and in distant organs settled tumor cells. This is the first report showing that CD44v6, alpha6beta4, Tspan8 and CXCR4 are biomarkers in PaCIC allowing for long-term survival, expansion and migration in immunocompromised mice. The stability of the percentage of PaCIC in  long-term and freshly-established lines after a roughly 8-fold enrichment by cloning indicates PaCIC, though required for long-term survival, concomitantly depending on support by non-CIC. © 2013 Wiley Periodicals, Inc.

 

----------------------------------------------------

[57]

TÍTULO / TITLE:  - Resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus: Role of type I interferon signaling.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Virology. 2013 Feb 5;436(1):221-34. doi: 10.1016/j.virol.2012.11.014. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.virol.2012.11.014

AUTORES / AUTHORS:  - Moerdyk-Schauwecker M; Shah NR; Murphy AM; Hastie E; Mukherjee P; Grdzelishvili VZ

INSTITUCIÓN / INSTITUTION:  - Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.

RESUMEN / SUMMARY:  - Oncolytic virus (OV) therapy takes advantage of common cancer characteristics, such as defective type I interferon (IFN) signaling, to preferentially infect and kill cancer cells with viruses. Our recent study (Murphy et al., 2012. J. Virol.  86, 3073-87) found human pancreatic ductal adenocarcinoma (PDA) cells were highly heterogeneous in their permissiveness to vesicular stomatitis virus (VSV) and suggested at least some resistant cell lines retained functional type I IFN responses. Here we examine cellular responses to infection by the oncolytic VSV recombinant VSV-DeltaM51-GFP by analyzing a panel of 11 human PDA cell lines for  expression of 33 genes associated with type I IFN pathways. Although all cell lines sensed infection by VSV-DeltaM51-GFP and most activated IFN-alpha and beta  expression, only resistant cell lines displayed constitutive high-level expression of the IFN-stimulated antiviral genes MxA and OAS. Inhibition of JAK/STAT signaling decreased levels of MxA and OAS and increased VSV infection, replication and oncolysis, further implicating IFN responses in resistance. Unlike VSV, vaccinia and herpes simplex virus infectivity and killing of PDA cells was independent of the type I IFN signaling profile, possibly because these two viruses are better equipped to evade type I IFN responses. Our study demonstrates heterogeneity in the type I IFN signaling status of PDA cells and suggests MxA and OAS as potential biomarkers for PDA resistance to VSV and other  OVs sensitive to type I IFN responses.

 

----------------------------------------------------

[58]

TÍTULO / TITLE:  - Thioredoxin-Mimetic Peptides (TXM) Reverse Auranofin Induced Apoptosis and Restore Insulin Secretion in Insulinoma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Pharmacol. 2013 Jan 14. pii: S0006-2952(13)00020-8. doi: 10.1016/j.bcp.2013.01.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bcp.2013.01.003

AUTORES / AUTHORS:  - Cohen-Kutner M; Khomsky L; Trus M; Aisner Y; Niv MY; Benhar M; Atlas D

INSTITUCIÓN / INSTITUTION:  - Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 919104, Israel.

RESUMEN / SUMMARY:  - The thioredoxin reductase/thioredoxin system (TrxR/Trx1) plays a major role in protecting cells from oxidative stress. Disruption of the TrxR-Trx1 system keeps  Trx1 in the oxidized state leading to cell death through activation of the ASK1-Trx1 apoptotic pathway. The potential mechanism and ability of tri- and tetra oligopeptides derived from the canonical -CxxC- motif of the Trx1-active site to mimic and enhance Trx1 cellular activity, was examined. The Trx mimetics  peptides (TXM) protected insulinoma INS832/13 cells from oxidative stress induced by selectively inhibiting TrxR with auranofin (AuF). TXM reversed the AuF-effects preventing apoptosis, and increasing cell-viability. The TXM peptides were effective in inhibiting AuF-induced MAPK, JNK and p38(MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation. The ability to form a disulfide-bridge-like conformation was estimated from molecular dynamics simulations. The TXM peptides restored insulin secretion and displayed Trx1 denitrosylase activity. Their potency was 10 to 100 fold higher than redox reagents like NAC, AD4, or ascorbic acid. Unable to reverse ERK1/2 phosphorylation, TXM-CB3 (NAc-Cys-Pro-Cys amide) appeared to function in part, through inhibiting ASK1-Trx dissociation. These highly effective anti-apoptotic effects of Trx1 mimetic peptides exhibited in INS832/13 cells could become valuable in treating adverse oxidative-stress related disorders such as diabetes.

 

----------------------------------------------------

[59]

TÍTULO / TITLE:  - Activation of TLR4 Is Required for the Synergistic Induction of Dual Oxidase 2 and Dual Oxidase A2 by IFN-gamma and Lipopolysaccharide in Human Pancreatic Cancer Cell Lines.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Immunol. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 4049/jimmunol.1201725

AUTORES / AUTHORS:  - Wu Y; Lu J; Antony S; Juhasz A; Liu H; Jiang G; Meitzler JL; Hollingshead M; Haines DC; Butcher D; Roy K; Doroshow JH

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular Pharmacology of the Center for Cancer Research, National  Cancer Institute, National Institutes of Health, Bethesda, MD 20892;

RESUMEN / SUMMARY:  - Pancreatitis is associated with release of proinflammatory cytokines and reactive oxygen species and plays an important role in the development of pancreatic cancer. We recently demonstrated that dual oxidase (Duox)2, an NADPH oxidase essential for reactive oxygen species-related, gastrointestinal host defense, is  regulated by IFN-gamma-mediated Stat1 binding to the Duox2 promoter in pancreatic tumor lines. Because LPS enhances the development and invasiveness of pancreatic  cancer in vivo following TLR4-related activation of NF-kappaB, we examined whether LPS, alone or combined with IFN-gamma, regulated Duox2. We found that upregulation of TLR4 by IFN-gamma in BxPC-3 and CFPAC-1 pancreatic cancer cells was augmented by LPS, resulting in activation of NF-kappaB, accumulation of NF-kappaB (p65) in the nucleus, and increased binding of p65 to the Duox2 promoter. TLR4 silencing with small interfering RNAs, as well as two independent  NF-kappaB inhibitors, attenuated LPS- and IFN-gamma-mediated Duox2 upregulation in BxPC-3 cells. Induction of Duox2 expression by IFN-gamma and LPS may result from IFN-gamma-related activation of Stat1 acting in concert with NF-kappaB-related upregulation of Duox2. Sustained extracellular accumulation of  H(2)O(2) generated by exposure to both LPS and IFN-gamma was responsible for an approximately 50% decrease in BxPC-3 cell proliferation associated with a G(1) cell cycle block, apoptosis, and DNA damage. We also demonstrated upregulation of Duox expression in vivo in pancreatic cancer xenografts and in patients with chronic pancreatitis. These results suggest that inflammatory cytokines can interact to produce a Duox-dependent pro-oxidant milieu that could increase the pathologic potential of pancreatic inflammation and pancreatic cancer cells.

 

----------------------------------------------------

[60]

TÍTULO / TITLE:  - Failure Patterns in Resected Pancreas Adenocarcinoma: Lack of Predicted Benefit to SMAD4 Expression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e31827fe9ce

AUTORES / AUTHORS:  - Winter JM; Tang LH; Klimstra DS; Liu W; Linkov I; Brennan MF; D’angelica MI; Dematteo RP; Fong Y; Jarnagin WR; O’reilly EM; Allen PJ

INSTITUCIÓN / INSTITUTION:  - *Department of Surgery, Thomas Jefferson University, Philadelphia, PA Departments of daggerPathology double daggerSurgery section signMedicine, Memorial Sloan-Kettering Cancer Center, New York, NY.

RESUMEN / SUMMARY:  - OBJECTIVE:: To determine whether SMAD4 expression is associated with recurrence pattern after resection for pancreatic ductal adenocarcinoma (PDA). BACKGROUND::  SMAD4 expression status has been reported to be associated with patterns of failure in PDA, but studies have not examined recurrence patterns after resection. METHODS:: A tissue microarray was constructed including 127 patients with resected PDA and either short-term (<12 months) or long-term (>30 months) survival. SMAD4 expression was evaluated by immunohistochemistry and categorized  as present or lost in tumor cells. Conventional pathologic features (lymph node metastases, positive resection margin, poor grade, and tumor size) were recorded, and disease-specific outcomes (eg, recurrence pattern and early cancer-specific mortality) were determined. RESULTS:: Loss of SMAD4 expression in pancreatic adenocarcinoma was identified in 40 of 127 patients (32%). SMAD4 loss occurred in 27% of patients who experienced isolated local recurrence, 33% of patients with a distant recurrence, 33% of patients who experienced local and distant site recurrences, and 25% of patients who were without evidence of recurrence (Fisher  exact, P = 0.9). In a multivariate analysis, the presence of regional lymph node  metastases was the only factor associated with the development of distant metastases (odds ratio = 4.7, P = 0.02). SMAD4 was neither associated with recurrence pattern (odds ratio = 0.9, P = 0.9) nor associated with early death (odds ratio = 0.5, P = 0.15). CONCLUSIONS:: Primary tumor SMAD4 expression status was not a predictor of recurrence pattern in a large cohort of patients with resected PDA.

 

----------------------------------------------------

[61]

TÍTULO / TITLE:  - Development and preliminary validation of the pancreatic cancer disease impact score.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Support Care Cancer. 2013 Jan 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00520-012-1713-3

AUTORES / AUTHORS:  - Heiberg T; Nordby T; Kvien TK; Buanes T

INSTITUCIÓN / INSTITUTION:  - Division of Cancer, Surgery and Transplantation, Oslo University Hospital, PO Box 4956, Oslo, 0424, Norway, Turid.Heiberg@ldh.no.

RESUMEN / SUMMARY:  - OBJECTIVE: Patient-reported outcomes are important for clinical practice and research, and should reflect what patients perceive as important. The objective of this study was to develop and preliminarily validate a brief, patient-derived, disease-specific tool, the pancreatic cancer disease impact (PACADI) score. METHODS: The development was performed in two phases. Forty-one patients with confirmed pancreatic cancer (PC) selected dimensions of health related to the impact of the disease. A weighting of the eight most frequently reported dimensions was performed in a second sample of 80 PC patients who also rated the  impact on eight numeric rating scales (NRS, range 0 to 10). The relative weights  and the scores from the NRS were used to compute the PACADI score (range 0 to 10). The patients also completed Edmonton Symptom Assessment System (ESAS) and EQ-5D. RESULTS: Dimensions reported by more than 20 % of the patients were included in the PACADI score (relative weights in parenthesis): pain/discomfort (0.16), fatigue (0.16), anxiety (0.15), bowel/digestive problems (0.14), loss of  appetite (0.13), dry mouth (0.11), itchiness (0.08), and nausea (0.07). The PACADI score in the 80 PC patients had a mean (SD) value of 3.26 (2.06) (95 % CI  2.80, 3.71), was moderately to strongly correlated to ESAS sense of well-being (r = 0.69) and EQ-5D (r = -0.52), and discriminated significantly between patients with and without PC. CONCLUSION: The PACADI score is a new eight-item, patient-derived, disease-specific measure. Preliminary validation regarding construct validity and discrimination encourages further validation in independent patient samples.

 

----------------------------------------------------

[62]

TÍTULO / TITLE:  - Prolonged survival and delayed progression of pancreatic intraepithelial neoplasia in LSL-KrasG12D/+;Pdx-1-Cre mice by vitamin E delta-tocotrienol.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt002

AUTORES / AUTHORS:  - Husain K; Centeno BA; Chen DT; Fulp WJ; Perez M; Zhang Lee G; Luetteke N; Hingorani SR; Sebti SM; Malafa MP

INSTITUCIÓN / INSTITUTION:  - Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.

RESUMEN / SUMMARY:  - The highly lethal nature of pancreatic cancer and the increasing recognition of high-risk individuals have made research into chemoprevention a high priority. Here, we tested the chemopreventive activity of delta-tocotrienol, a bioactive vitamin E derivative extracted from palm fruit, in the LSL-Kras(G12D/+);Pdx-1-Cre pancreatic cancer mouse model. At 10 weeks of age, mice (n = 92) were randomly allocated to three groups: (i) no treatment; (ii) vehicle and (iii) delta-tocotrienol (200mg/kg x 2/day, PO). Treatment was continued for 12 months.  Mice treated with delta-tocotrienol showed increased median survival from the onset of treatment (11.1 months) compared with vehicle-treated mice (9.7 months)  and non-treated mice (8.5 months; P < 0.025). Importantly, none of the mice treated with delta-tocotrienol harbored invasive cancer compared with 10% and 8%  in vehicle-treated and non-treated mice, respectively. Furthermore, delta-tocotrienol treatment also resulted in significant suppression of mouse pancreatic intraepithelial neoplasm (mPanIN) progression compared with vehicle-treated and non-treated mice: mPanIN-1: 47-50% (P < 0.09), mPanIN-2: 6-11% (P < 0.001), mPanIN-3: 3-15% (P < 0.001) and invasive cancer: 0-10% (P < 0.001). delta-Tocotrienol treatment inhibited mutant Kras-driven pathways such as MEK/ERK, PI3K/AKT and NF-kB/p65, as well as Bcl-xL and induced p27. delta-Tocotrienol also induced biomarkers of apoptosis such as Bax and activated  caspase 3 along with an increase in plasma levels of CK18. In summary, delta-tocotrienol’s ability to interfere with oncogenic Kras pathways coupled with the observed increase in median survival and significant delay in PanIN progression highlights the chemopreventative potential of delta-tocotrienol and warrants further investigation of this micronutrient in individuals at high risk  for pancreatic cancer.

 

----------------------------------------------------

[63]

TÍTULO / TITLE:  - The Clinical Efficacy and Safety of Modified Miwa’s Augmented Regional Pancreatoduodenectomy in the Treatment of Ductal Adenocarcinoma of the Pancreas in the Uncinate Process.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hepatogastroenterology. 2012 Dec 16;60(122). doi: 10.5754/hge12713.

            ●● Enlace al texto completo (gratuito o de pago) 5754/hge12713

AUTORES / AUTHORS:  - Jing W; He T; Hu X; Jin G; Shao C; Li G; Song B; Zhang Y

RESUMEN / SUMMARY:  - Background/Aims: En bloc resection of a tumor located in the uncinate process of  the pancreas is a challenging problem. The aim of this study was to analyze outcomes of modified Miwa’s augmented regional pancreatoduodenectomy for patients with pancreatic cancer in the uncinate process involving the root of the mesentery. Methodology: We analyzed by summarizing the 48 cases of ductal adenocarcinoma in the uncinate process of the pancreas during January 2004 to December 2010 with Miwa’s augmented regional pancreatoduodenectomy in our hospital and examined the clinical effect and safety of this procedure. Results:  We performed extended pancreaticoduodenectomy combined with isolation of full-length superior mesentery artery (SMA) for 48 patients. Sixteen of the forty-eight patients were combined with PV/SMV resection and reconstruction. There was no operative death and 20 cases developed complications, including mild to severe diarrhea in 17 cases. During follow-up survey among all patients of 6 to 45 months (median 20 months), 9 died of liver metastasis, 10 died of local recurrence, and 5 died of non-tumor causes. The 1-, 2- and 3-year accumulated survival rates were 69.1%, 35.1% and 20.2%, respectively. Conclusions: Full-length SMA isolation and involved mesentery resection with extended pancreaticoduodenectomy is safe and effective.

 

----------------------------------------------------

[64]

TÍTULO / TITLE:  - A Resequence Analysis of Genomic Loci on Chromosomes 1q32.1, 5p15.33, and 13q22.1 Associated With Pancreatic Cancer Risk.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318264cea5

AUTORES / AUTHORS:  - Parikh H; Jia J; Zhang X; Chung CC; Jacobs KB; Yeager M; Boland J; Hutchinson A; Burdett L; Hoskins J; Risch HA; Stolzenberg-Solomon RZ; Chanock SJ; Wolpin BM; Petersen GM; Fuchs CS; Hartge P; Amundadottir L

INSTITUCIÓN / INSTITUTION:  - From the *Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, daggerDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD; double daggerCore Genotyping Facility, SAIC-Frederick, Inc, NCI-Frederick, Frederick, MD; section signYale University School of Public Health, School of Medicine, New Haven, CT; parallelDepartment of Medical Oncology, Dana-Farber Cancer Institute, and paragraph signChanning Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; and #Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

RESUMEN / SUMMARY:  - OBJECTIVE: The objective of this study was to fine-map common pancreatic cancer susceptibility regions. METHODS: We conducted targeted Roche-454 resequencing across 428 kb in 3 genomic regions identified in genome-wide association studies  (GWAS) of pancreatic cancer, on chromosomes 1q32.1, 5p15.33, and 13q22.1. RESULTS: An analytical pipeline for calling genotypes was developed using HapMap  samples sequenced on chr5p15.33. Concordance to 1000 Genomes data for chr5p15.33  was greater than 96%. The concordance for chr1q32.1 and chr13q22.1 with pancreatic cancer GWAS data was greater than 99%. Between 9.2% and 19.0% of variants detected were not present in 1000 Genomes for the respective continental population. The majority of completely novel single-nucleotide polymorphisms (SNPs) were less common (minor allele frequency [MAF], </=5%) or rare (MAF, </=2%), illustrating the value of enlarging test sets for discovery of less common variants. Using the data set, we examined haplotype blocks across each region using a tag SNP analysis (r > 0.8 for MAF of >/=5%) and determined that at least 196, 243, and 63 SNPs are required for fine-mapping chr1q32.1, chr5p15.33,  and chr13q22.1, respectively, in European populations. CONCLUSIONS: We have characterized germline variation in 3 regions associated with pancreatic cancer risk and show that targeted resequencing leads to the discovery of novel variants and improves the completeness of germline sequence variants for fine-mapping GWAS susceptibility loci.

 

----------------------------------------------------

[65]

TÍTULO / TITLE:  - Flavonoid intake and risk of pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study Cohort.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 8. doi: 10.1038/bjc.2012.584.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2012.584

AUTORES / AUTHORS:  - Arem H; Bobe G; Sampson J; Subar AF; Park Y; Risch H; Hollenbeck A; Mayne ST; Stolzenberg-Solomon RZ

INSTITUCIÓN / INSTITUTION:  - 1] Yale School of Public Health, New Haven, CT, USA [2] Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

RESUMEN / SUMMARY:  - Background:Limited epidemiological studies show inverse associations between dietary flavonoid intake and pancreatic cancer risk, but results are inconsistent and are based on few cases. We examined the association between intake of flavonoids and pancreatic cancer risk in the large, prospective National Institutes of Health-AARP Diet and Health Study Cohort.Methods:During follow-up through 2006 (median follow-up 10.6 years), 2379 pancreatic cancer cases were identified. We used Cox proportional hazards modelling to estimate hazard ratios  (HRs) and 95% confidence intervals (CIs).Results:We found no association between  total flavonoid intake (Q5 vs Q1 HR=1.09, 95% CI: 0.96-1.24) or any flavonoid subtypes and pancreatic cancer risk. Significant interactions were not observed by age, sex, smoking status, BMI or diabetes.Conclusion:Our results do not support the hypothesis that flavonoids have a protective role in pancreatic cancer carcinogenesis.British Journal of Cancer advance online publication, 8 January 2013; doi:10.1038/bjc.2012.584 www.bjcancer.com.

 

----------------------------------------------------

[66]

TÍTULO / TITLE:  - Intraductal tubular adenoma of the pancreas as a possible rare variant of gastric-type intraductal papillary mucinous neoplasm: a report of two cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anal Quant Cytol Histol. 2012 Dec;34(6):325-30.

AUTORES / AUTHORS:  - Teng X; Xue D; Lai M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang  University, Hangzhou 310058, China.

RESUMEN / SUMMARY:  - BACKGROUND: Intraductal tubular adenoma (ITA) of the pancreas has been reported recently, but no more than 20 cases have been documented. Two cases of ITA are described in order to investigate histogenesis and discuss the relationship between ITA and intraductal papillary mucinous neoplasm (IPMN). CASE: Two patients were hospitalized because of midsection discomfort and pancreatic mass.  Both tumors presented as polypoid tumor in the cysts, located in the main pancreatic duct. Histologically they were composed of closely packed tubular glands or had a branching tubular growth pattern mimicking pyloric-type glands. The epithelia within the same cyst appeared typical of gastric IPMN. Pancreatic intraepithelial neoplasia (PanIN) IA and IB were present in smaller ducts around  the tumors in both cases. The tumors predominantly showed neutral mucin. CK7 and  MUCSAC stains were positive, whereas MUC1, MUC2, CK20 and CDX2 were negative; both of the IPMNs and associated PanINs shared the same immunohistochemical profile. The 2 patients had no recurrence of disease at 142 months and 38 months  postoperatively, respectively. CONCLUSION: ITA is a rare, benign tumor almost always accompanied by gastric-type IPMN. It may be a variant of gastric-type IPMN. Smaller ducts around the tumor with low-grade PanIN are one of the features of the tumor.

 

----------------------------------------------------

[67]

TÍTULO / TITLE:  - CA19-9 in Potentially Resectable Pancreatic Cancer: Perspective to Adjust Surgical and Perioperative Therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2809-1

AUTORES / AUTHORS:  - Hartwig W; Strobel O; Hinz U; Fritz S; Hackert T; Roth C; Buchler MW; Werner J

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

RESUMEN / SUMMARY:  - PURPOSE: In pancreatic cancer, genetic markers to aid clinical decision making are still lacking. The present study was designed to determine the prognostic role of perioperative serum tumor marker carbohydrate antigen 19-9 (CA19-9) in pancreatic adenocarcinoma, with a focus on implications for pre- and postoperative therapeutic consequences. METHODS: Of a total of 1,626 consecutive  patients who underwent surgery for primary pancreatic adenocarcinoma, data from 1,543 patients with preoperative serum levels of CA19-9 were evaluated for tumor  stage, resectability, and prognosis. Preoperative to postoperative CA19-9 changes were analyzed for long-term survival. A control cohort of 706 patients with chronic pancreatitis was used to assess the predictability of malignancy by CA19-9 and the effects of hyperbilirubinemia on CA19-9 levels. RESULTS: The more  that preoperative CA19-9 increased, the lower were tumor resectability and survival rates. Resectability and 5-year survival varied from 80 to 38 % and from 27 to 0 % for CA19-9 <37 versus >/=4,000 U/ml, respectively. The R0 resection rate was as low as 15 % in all patients with CA19-9 levels >/=1,000 U/ml. CA19-9  increased with the stage of the disease and was highest in AJCC stage IV. Patients with an early postoperative CA19-9 increase had a dismal prognosis. Hyperbilirubinemia did not markedly affect CA19-9 levels (correlation coefficient </=0.135). CONCLUSIONS: In patients with pancreatic adenocarcinoma, CA19-9 predicts resectability, stage of disease, as well as survival. Highly elevated preoperative or increasing postoperative CA19-9 levels are associated with low resectability and poor survival rates, and demand the adjustment of surgical and  perioperative therapy.

 

----------------------------------------------------

[68]

TÍTULO / TITLE:  - Antioxidant intake and pancreatic cancer risk: The Vitamins and Lifestyle (VITAL) Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer. 2012 Dec 21. doi: 10.1002/cncr.27936.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27936

AUTORES / AUTHORS:  - Han X; Li J; Brasky TM; Xun P; Stevens J; White E; Gammon MD; He K

INSTITUCIÓN / INSTITUTION:  - Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; American Cancer Society, Atlanta, Georgia. xuesong.han@cancer.org.

RESUMEN / SUMMARY:  - BACKGROUND: Oxidative stress causes damage to many components of human cells (ie, proteins, lipids, and DNA) and is involved in carcinogenesis. Nutrients with antioxidant properties may protect against oxidative stress. In this study, the authors examined the intake of antioxidants from diet and supplements in relation to pancreatic cancer risk among participants of the Vitamins and Lifestyle (VITAL) Study. METHODS: The participants included 77,446 men and women ages 50 to 76 years who were residents of western Washington State and who completed a baseline questionnaire between 2000 and 2002. Participants reported usual diet over the past year and use of supplements over the past 10 years in addition to demographic and lifestyle factors. During a median follow-up of 7.1 years, 184 participants developed pancreatic adenocarcinoma. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for 7 antioxidants: beta-carotene, lutein plus zeaxanthin, lycopene, vitamin C, vitamin E, selenium, and zinc. RESULTS: An inverse association was observed between dietary selenium and the risk of pancreatic cancer (medium vs low intake: HR, 0.58; 95% CI, 0.35-0.94; high vs low intake: HR, 0.44; 95% CI, 0.23-0.85; P(trend) = .01); however, when supplemental  and dietary exposures were combined, the association was no longer statistically  significant. CONCLUSIONS: Dietary selenium intake was inversely associated with the risk of pancreatic cancer, and the observed association was attenuated by selenium supplementation. Cancer 2012. © 2012 American Cancer Society.

 

----------------------------------------------------

[69]

TÍTULO / TITLE:  - Intravenous genetic mesothelin vaccine based on human adenovirus 40 inhibits growth and metastasis of pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Cancer. 2012 Dec 11. doi: 10.1002/ijc.27983.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.27983

AUTORES / AUTHORS:  - Yamasaki S; Miura Y; Davydova J; Vickers SM; Yamamoto M

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University of Minnesota, Minneapolis, MN.

RESUMEN / SUMMARY:  - High pancreatic cancer mortality and poor prognosis are caused by the difficulty  for early diagnosis and extremely low rates of resection because of metastasis. Mesothelin overexpression in pancreatic cancer is a remarkable biomarker for tumor progression, especially for invasion and metastasis. Here, we generated a novel replication-defective recombinant adenovirus 40 (rAd40), whose gene delivery properties are totally different from a conventional rAd5. In this study, we have identified intravenous administration with rAd40 expressing mouse  mesothelin (Msln) as an effective prophylactic cancer vaccine against metastatic  lesions of pancreatic cancer in mice. Intravenous administration of rAd40 (rAd40  i.v.) achieved transgene delivery in wider range of organs compared to rAd5 i.v., while rAd5 was distributed mainly to the liver, spleen, and lungs. Additionally,  rAd40 i.v. showed less transduction of the liver or inflammatory responses, resulted in reduced liver toxicity compared to rAd5 i.v. Also, more robust systemic antigen-specific immune responses were stimulated by rAd40 i.v. Pretreatment with a single ovalbumin-expressing rAd40 i.v. prevented tumor growth in mouse subcutaneous models of ovalbumin-expressing pancreatic cancer. When used with Msln-expressing rAd40 i.v., Msln protein expression and metastases were suppressed in a syngeneic orthotopic mouse model of pancreatic cancer, corresponding to the detection of Msln- and tumor-specific cytotoxic T lymphocyte (CTL). Our novel methods generated antitumor effects against antigen-expressing tumors through antigen- and tumor-specific CTL-mediated immunity. Thus, our results indicate that a rAd40-based intravenous vaccine provides a new strategy for the effective control of metastatic pancreatic cancer and novel therapy against other cancers and infectious diseases.

 

----------------------------------------------------

[70]

TÍTULO / TITLE:  - Targeting the Yin and the Yang: Combined Inhibition of the Tyrosine Kinase c-Src  and the Tyrosine Phosphatase SHP-2 Disrupts Pancreatic Cancer Signaling and Biology In Vitro and Tumor Formation In Vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e3182793fd7

AUTORES / AUTHORS:  - Gomes EG; Connelly SF; Summy JM

INSTITUCIÓN / INSTITUTION:  - From the Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando, FL.

RESUMEN / SUMMARY:  - OBJECTIVES: Although c-Src (Src) has emerged as a potential pancreatic cancer target in preclinical studies, Src inhibitors have not demonstrated a significant therapeutic benefit in clinical trials. The objective of these studies was to examine the effects of combining Src inhibition with inhibition of the protein tyrosine phosphatase SHP-2 in pancreatic cancer cells in vitro and in vivo. METHODS: SHP-2 and Src functions were inhibited by siRNA or small molecule inhibitors. The effects of dual Src/SHP-2 functional inhibition were evaluated by Western blot analysis of downstream signaling pathways; cell biology assays to examine caspase activity, viability, adhesion, migration, and invasion in vitro;  and an orthotopic nude mouse model to observe pancreatic tumor formation in vivo. RESULTS: Dual targeting of Src and SHP-2 induces an additive or supra-additive loss of phosphorylation of Akt and ERK-1/2 and corresponding increases in expression of apoptotic markers, relative to targeting either protein individually. Combinatorial inhibition of Src and SHP-2 significantly reduces viability, adhesion, migration, and invasion of pancreatic cancer cells in vitro  and tumor formation in vivo, relative to individual Src/SHP-2 inhibition. CONCLUSIONS: These data suggest that the antitumor effects of Src inhibition in pancreatic cancer may be enhanced through simultaneous inhibition of SHP-2.

 

----------------------------------------------------

[71]

TÍTULO / TITLE:  - Type 2 diabetes mellitus and survival in pancreatic adenocarcinoma: A retrospective cohort study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer. 2013 Jan 15;119(2):404-10. doi: 10.1002/cncr.27731. Epub 2012 Aug 1.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27731

AUTORES / AUTHORS:  - Hwang A; Narayan V; Yang YX

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania.

RESUMEN / SUMMARY:  - BACKGROUND: Recent evidence has identified pre-existing type 2 diabetes mellitus  (T2DM) as a risk factor for the development of PAC, but relatively little is known about its effects on survival. Our aim was to determine the effect of varying durations of pre-existing T2DM on survival in patients with PAC. METHODS: We conducted a retrospective cohort study using The Health Improvement Network (THIN), a primary care electronic medical record database from the UK (2003-2010). The study cohort included all subjects with a diagnostic code for PAC. Subjects with a diagnostic code for T2DM before their PAC diagnosis were classified as exposed; otherwise, subjects were classified as unexposed. The primary outcome was overall survival. The analysis was performed using univariate and multivariable Cox proportional-hazards models. Additional analysis was performed to assess the effect of increasing duration of pre-existing T2DM [i.e., <90 days, 90 days to <1 year, 1 to <3 years, 3 to 5 years, >5 years] on survival. RESULTS: The study included 3,147 patients with PAC, with 745 patients having pre-existing T2DM and 2,402 patients without pre-existing T2DM. In the primary multivariate analysis, there was no difference in survival between those exposed  and those unexposed to pre-existing T2DM (HR 1.02 [0.93, 1.12], p = 0.620). In the secondary analysis, only those patients with T2DM > 5 years duration had a significantly increased mortality (HR 1.16 [1.00, 1.33], p < 0.05). CONCLUSIONS:  Long-term pre-existing T2DM is associated with increased mortality in patients diagnosed with PAC. Cancer 2013. © 2012 American Cancer Society.

 

----------------------------------------------------

[72]

TÍTULO / TITLE:  - SOX15 is a candidate tumor suppressor in pancreatic cancer with a potential role  in Wnt/beta-catenin signaling.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncogene. 2013 Jan 14. doi: 10.1038/onc.2012.595.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2012.595

AUTORES / AUTHORS:  - Thu KL; Radulovich N; Becker-Santos DD; Pikor LA; Pusic A; Lockwood WW; Lam WL; Tsao MS

INSTITUCIÓN / INSTITUTION:  - BC Cancer Research Centre, Vancouver, BC, Canada.

RESUMEN / SUMMARY:  - Pancreatic cancer is among the top five deadliest cancers in developed countries. Better knowledge of the molecular mechanisms contributing to its tumorigenesis is imperative to improve patient prognosis. Identification of novel tumor suppressor genes (TSGs) in pancreatic cancer will reveal new mechanisms of pathway deregulation and will ultimately help improve our understanding of this aggressive disease. According to Knudson’s two-hit model, TSGs are classically disrupted by two concerted genetic events. In this study, we combined DNA methylation profiling with copy number and mRNA expression profiling to identify  novel TSGs in a set of 20 pancreatic cancer cell lines. These data sets were integrated for each of approximately 12 000 genes in each cell line enabling the  elucidation of those genes that undergo DNA hypermethylation, copy-number loss and mRNA downregulation simultaneously in multiple cell lines. Using this integrative genomics strategy, we identified SOX15 (sex determining region Y-box  15) as a candidate TSG in pancreatic cancer. Expression of SOX15 in pancreatic cancer cell lines with undetectable expression resulted in reduced viability of cancer cells both in vitro and in vivo demonstrating its tumor suppressive capability. We also found reduced expression, homozygous deletion and aberrant DNA methylation of SOX15 in clinical pancreatic tumor data sets. Furthermore, we  deduced a novel role for SOX15 in suppressing the Wnt/beta-catenin signaling pathway, which we hypothesize is a pathway through which SOX15 may exert its tumor suppressive effects in pancreatic cancer.Oncogene advance online publication, 14 January 2013; (2012) 0, 000-000. doi:10.1038/onc.2012.595.

 

----------------------------------------------------

[73]

TÍTULO / TITLE:  - Knockdown of Pyruvate Carboxylase or Fatty Acid Synthase Lowers Numerous Lipids and Glucose-Stimulated Insulin Release in Insulinoma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Biochem Biophys. 2013 Jan 25. pii: S0003-9861(13)00007-6. doi: 10.1016/j.abb.2013.01.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.abb.2013.01.002

AUTORES / AUTHORS:  - Macdonald MJ; Hasan NM; Dobrzyn A; Stoker SW; Ntambi JM; Liu X; Sampath H

INSTITUCIÓN / INSTITUTION:  - Childrens Diabetes Center, University of Wisconsin School of Medicine and Public  Health, Madison, WI 53706. Electronic address: mjmacdon@wisc.edu.

RESUMEN / SUMMARY:  - We previously showed that knockdown of the anaplerotic enzyme pyruvate carboxylase in the INS-1 832/13 insulinoma cell line inhibited glucose-stimulated insulin release and glucose carbon incorporation into lipids. We now show that knockdown of fatty acid synthase (FAS) mRNA and protein also inhibits glucose-stimulated insulin release in this cell line. Levels of numerous phospholipids, cholesterol esters, diacylglycerol, triglycerides and individual fatty acids with C(14)-C(24) side chains were acutely lowered about 20% in glucose-stimulated pyruvate carboxylase knockdown cells over a time course that coincides with insulin secretion. In FAS knockdown cells glucose carbon incorporation into lipids and the levels of the subclasses of phospholipids and cholesterol ester species were lower by 20-30% without inhibition of glucose oxidation. These studies suggest that rapid lipid modification is essential for normal glucose-stimulated insulin secretion.

 

----------------------------------------------------

[74]

TÍTULO / TITLE:  - Gastroenteropancreatic neuroendocrine tumors: role of imaging in diagnosis and management.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiology. 2013 Jan;266(1):38-61. doi: 10.1148/radiol.12112512.

            ●● Enlace al texto completo (gratuito o de pago) 1148/radiol.12112512

AUTORES / AUTHORS:  - Sahani DV; Bonaffini PA; Fernandez-Del Castillo C; Blake MA

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Division of Abdominal Imaging and Interventional Radiology, and Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, White 270, Boston, MA 02114.

RESUMEN / SUMMARY:  - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of neoplasms that arise from cells of the diffuse neuroendocrine system and are characterized by a wide spectrum of clinical manifestations. All NETs are potentially malignant but differ in their biologic characteristics and the probability of metastatic disease. The pathologic classification of these tumors  relies on their proliferation and differentiation. In the past decades, several nomenclatures have been proposed to stratify neuroendocrine tumors, but the World Health Organization classification is the one that is most widely accepted and used. The diagnosis of neuroendocrine tumor relies on clinical manifestation, laboratory parameters, imaging features, and tissue biomarkers in a biopsy specimen. With improved understanding of the natural history and lesion biology,  management of GEP-NETs has also evolved. Although surgery remains the only potentially curative therapy for patients with primary GEP-NETs, other available  treatments include chemotherapy, interferon, somatostatin analogs, and targeted therapies. Recent improvements in both morphologic and functional imaging methods have contributed immensely to patient care. Morphologic imaging with contrast agent-enhanced multidetector computed tomography and magnetic resonance imaging is most widely used for initial evaluation and staging of disease in these patients, whereas functional imaging techniques are useful both for detection and prognostic evaluation and can change treatment planning. ©RSNA, 2013.

 

----------------------------------------------------

[75]

TÍTULO / TITLE:  - Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Causes Control. 2013 Jan 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10552-012-0138-0

AUTORES / AUTHORS:  - Leenders M; Bhattacharjee S; Vineis P; Stevens V; Bueno-de-Mesquita HB; Shu XO; Amundadottir L; Gross M; Tobias GS; Wactawski-Wende J; Arslan AA; Duell EJ; Fuchs CS; Gallinger S; Hartge P; Hoover RN; Holly EA; Jacobs EJ; Klein AP; Kooperberg C; Lacroix A; Li D; Mandelson MT; Olson SH; Petersen G; Risch HA; Yu K; Wolpin BM; Zheng W; Agalliu I; Albanes D; Boutron-Ruault MC; Bracci PM; Buring JE; Canzian F; Chang K; Chanock SJ; Cotterchio M; Gaziano JM; Giovanucci EL; Goggins M; Hallmans G; Hankinson SE; Hoffman-Bolton JA; Hunter DJ; Hutchinson A; Jacobs KB; Jenab M; Khaw KT; Kraft P; Krogh V; Kurtz RC; McWilliams RR; Mendelsohn JB; Patel AV; Rabe KG; Riboli E; Tjonneland A; Trichopoulos D; Virtamo J; Visvanathan K; Elena JW; Yu H; Zeleniuch-Jacquotte A; Stolzenberg-Solomon RZ

INSTITUCIÓN / INSTITUTION:  - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK, M.Leenders-6@umcutrecht.nl.

RESUMEN / SUMMARY:  - PURPOSE: The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related  to OCM and PanCa was assessed. METHODS: Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association  with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (<0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition. RESULTS: When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers. CONCLUSIONS: This is the largest genetic study to date to  examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis.

 

----------------------------------------------------

[76]

TÍTULO / TITLE:  - ICAT is a novel PTF1A interactor that regulates pancreatic acinar differentiation and displays altered expression in tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem J. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1042/BJ20120873

AUTORES / AUTHORS:  - Campos ML; Sanchez-Arevalo Lobo V; Rodolosse A; Gottardi CJ; Mafficini A; Beghelli S; Scardoni M; Bassi C; Scarpa A; Real FX

RESUMEN / SUMMARY:  - The Pancreas Transcription Factor 1 (PTF1) complex is a master regulator of differentiation of acinar cells, responsible for the production of digestive enzymes. In the adult pancreas, PTF1 contains two pancreas-restricted transcription factors: Ptf1a and Rbpjl. PTF1 recruits P/CAF which acetylates Ptf1a and enhances its transcriptional activity. Using a yeast two hybrid screening, we identified ICAT (Inhibitor of ss-Catenin and Tcf4) as a novel Ptf1a interactor. ICAT regulates the Wnt pathway and cell proliferation. We validated and mapped the ICAT-Ptf1a interaction in vitro and in vivo. We demonstrated that  - upon its overexpression in acinar tumor cells - ICAT negatively regulates PTF1  activity in vitro and in vivo. This effect was independent of beta-catenin and was mediated by direct binding to Ptf1a and displacement of P/CAF. ICAT also modulated the expression of Pdx1 and Sox9 in acinar tumor cells. ICAT overexpression reduced the interaction of Ptf1a with Rbpjl and P/CAF and impaired Ptf1a acetylation by P/CAF. ICAT did not affect the subcellular localization of Ptf1a. In human pancreas, ICAT displayed a cell-type specific distribution: in acinar and endocrine cells it was nuclear; in ductal cells, it was cytoplasmic. In ductal adenocarcinomas, ICAT displayed mainly a nuclear or mixed distribution  and the former was an independent marker of survival. ICAT regulates acinar differentiation and it does so through a novel, Wnt pathway-independent, mechanism that may contribute to pancreatic disease.

 

----------------------------------------------------

[77]

TÍTULO / TITLE:  - Factors Determining Diagnostic Yield of Endoscopic Ultrasound Guided Fine-Needle  Aspiration for Pancreatic Cystic Lesions: A Multicentre Asian Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Dig Dis Sci. 2013 Jan 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10620-012-2528-2

AUTORES / AUTHORS:  - Lim LG; Lakhtakia S; Ang TL; Vu CK; Dy F; Chong VH; Khor CJ; Lim WC; Doshi BK; Varadarajulu S; Yasuda K; Wong JY; Chan YH; Nga ME; Ho KY

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology and Hepatology, National University Health System, 10 Kent Ridge Crescent, Singapore, 119260, Singapore.

RESUMEN / SUMMARY:  - BACKGROUND AND AIM: The purpose of this study was to determine (1) the diagnostic yield for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with pancreatic cystic lesions, (2) additional value of EUS-FNA over EUS alone in the diagnosis of pancreatic cysts, and (3) diagnostic sensitivity and specificity of EUS and EUS-FNA in the subset of patients where histopathology of  surgical specimens were available. METHODS: All patients who underwent EUS examination for the evaluation of pancreatic cystic lesions in six Asian centres  were included in the study. RESULTS: Of 298 patients with pancreatic cysts who underwent EUS, 132 (44.3 %) underwent FNA. In the entire cohort, pseudocysts and  intraductal papillary mucinous neoplasm (IPMN) were the predominant cystic lesions. The cytologic yield of EUS-FNA was 47 %. On univariate analysis, factors associated with higher cytologic yield included vascular involvement on EUS, presence of solid cystic component, and increased number of needle passes during  EUS-FNA. On multivariate analysis, presence of solid cystic components and increased number of needle passes during EUS-FNA were associated with higher diagnostic yield of EUS-FNA. For pancreatic cysts with a solid component, the diagnostic yield of EUS-FNA increased significantly from 44 % with one pass to 78 % with more than one pass (p = 0.016). In the absence of a solid component, the diagnostic yield was 29 % with one pass and was not significantly different from  the diagnostic yield of 50 % with more than one pass, p = 0.081. CONCLUSION: The  cytologic yield of EUS-FNA was 47 %. When a solid component was present in the cyst, doing more than one pass during EUS-FNA increased its diagnostic yield.

 

----------------------------------------------------

[78]

TÍTULO / TITLE:  - Expression of NEDD9 in pancreatic ductal adenocarcinoma and its clinical significance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-012-0624-8

AUTORES / AUTHORS:  - Xue YZ; Sheng YY; Liu ZL; Wei ZQ; Cao HY; Wu YM; Lu YF; Yu LH; Li JP; Li ZS

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, The Third Hospital Affiliated to Nantong University, No. 585, Xingyuan North RD, Wuxi, 214041, Jiangsu Province, China, xueyz2008@yahoo.com.cn.

RESUMEN / SUMMARY:  - The aim of this study was to investigate the expression and prognostic significance of NEDD9 in pancreatic ductal adenocarcinoma (PDA). Expressional levels of NEDD9 mRNA and protein in paired pancreatic cancer lesions and adjacent noncancerous tissues were examined by quantitative real-time PCR and western blotting. NEDD9 expression was analyzed by immunohistochemistry in 106 patients with PDA. The correlations between NEDD9 immunostaining levels and clinicopathologic factors, as well as the follow-up data of patients, were analyzed statistically. NEDD9 protein and mRNA levels were elevated in pancreatic carcinoma lesions compared with the paired adjacent noncancerous tissues. A high  level of expression of NEDD9 was significantly correlated with clinical staging (P < 0.001), lymph node metastasis (P < 0.001), and histological differentiation  (P < 0.001). Patients with a higher NEDD9 expression had a significantly shorter  survival time than those patients with lower NEDD9 expression. The multivariate analysis revealed that NEDD9 could serve as an independent factor of poor prognosis. Our finding indicates that NEDD9 could be used as prognostic molecular marker and therapeutic target for PDA.

 

----------------------------------------------------

[79]

TÍTULO / TITLE:  - Potential role of acid ceramidase in conversion of cytostatic to cytotoxic end-point in pancreatic cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-012-2050-4

AUTORES / AUTHORS:  - Morad SA; Messner MC; Levin JC; Abdelmageed N; Park H; Merrill AH Jr; Cabot MC

INSTITUCIÓN / INSTITUTION:  - Department of Experimental Therapeutics, John Wayne Cancer Institute, 2200 Santa  Monica Blvd, Santa Monica, CA, 90404, USA.

RESUMEN / SUMMARY:  - PURPOSE: Acid ceramidase (AC) occupies an important place in the control of cancer cell proliferation. We tested the influence of AC inhibition on the effects of PSC 833, a P-glycoprotein antagonist with potent ceramide-generating capacity, to determine whether AC could be a therapeutic target in pancreatic cancer. METHODS: Ceramide metabolism was followed using (3)H-palmitate, and molecular species were determined by mass spectroscopy. Apoptosis was measured by DNA fragmentation, autophagy by acridine orange staining, and cell cycle was assessed by flow cytometry and RB phosphorylation. AC was measured in intact cells using fluorescent substrate. RESULTS: Exposure of human PANC-1 or MIA-PaCa-2 cells to PSC 833 promoted increases in de novo (dihydro)ceramides, (dihydro)glucosylceramides, and (dihydro)sphingomyelins, demarking ceramide generation and robust metabolism. Despite the multifold increases in (dihydro)ceramide levels, cells were refractory to PSC 833. However, PSC 833 produced a dose-dependent decrease in DNA synthesis and dose- and time-dependent  decreases in RB phosphorylation, consistent with cell cycle arrest as demonstrated at G1. Cytostatic effects of PSC 833 were converted to cytotoxic end-point by acid ceramidase inhibition. Cytotoxicity was accompanied by formation of acridine orange-stained acidic vesicles and an increase in LC3 expression, indicative of autophagic response. Cell death was not reversed by preexposure to myriocin, which blocks PSC 833-induced ceramide generation. CONCLUSION: Although the role of ceramide in end-point cytotoxicity is unclear, our results suggest that acid ceramidase is a viable target in pancreatic cancer. We propose that AC inhibition will be effective in concert with other anticancer  therapies.

 

----------------------------------------------------

[80]

TÍTULO / TITLE:  - The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncogene. 2013 Jan 14. doi: 10.1038/onc.2012.631.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2012.631

AUTORES / AUTHORS:  - Kang R; Tang D; Schapiro NE; Loux T; Livesey KM; Billiar TR; Wang H; Van Houten B; Lotze MT; Zeh HJ

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.

RESUMEN / SUMMARY:  - Tumor cells require increased adenosine triphosphate (ATP) to support anabolism and proliferation. The precise mechanisms regulating this process in tumor cells  are unknown. Here, we show that the receptor for advanced glycation endproducts (RAGE) and one of its primary ligands, high-mobility group box 1 (HMGB1), are required for optimal mitochondrial function within tumors. We found that RAGE is  present in the mitochondria of cultured tumor cells as well as primary tumors. RAGE and HMGB1 coordinately enhanced tumor cell mitochondrial complex I activity, ATP production, tumor cell proliferation and migration. Lack of RAGE or inhibition of HMGB1 release diminished ATP production and slowed tumor growth in  vitro and in vivo. These findings link, for the first time, the HMGB1-RAGE pathway with changes in bioenergetics. Moreover, our observations provide a novel mechanism within the tumor microenvironment by which necrosis and inflammation promote tumor progression.Oncogene advance online publication, 14 January 2013; doi:10.1038/onc.2012.631.

 

----------------------------------------------------

[81]

TÍTULO / TITLE:  - Molecular Markers for Novel Therapeutic Strategies in Pancreatic Endocrine Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826cb243

AUTORES / AUTHORS:  - Gilbert JA; Adhikari LJ; Lloyd RV; Halfdanarson TR; Muders MH; Ames MM

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Molecular Pharmacology and Experimental Therapeutics, daggerLaboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; double daggerUniversity of Wisconsin School of Medicine, Madison, WI; section signDepartment of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA; and parallelInstitute of Pathology, University Hospital Carl Gustav Carus, Dresden, Germany.

RESUMEN / SUMMARY:  - OBJECTIVES: Pancreatic endocrine tumors (PETs) share numerous features with gastrointestinal neuroendocrine (carcinoid) tumors. Targets of novel therapeutic  strategies previously assessed in carcinoid tumors were analyzed in PETs (44 cases). METHODS: Activating mutations in EGFR, KIT, and PDGFRA and nonresponse mutations in KRAS were evaluated. Copy number of EGFR and HER-2/neu was quantified by fluorescence in situ hybridization. Expression of EGFR, PDGFRA, VEGFR1, TGFBR1, Hsp90, SSTR2A, SSTR5, IGF1R, mTOR, and MGMT was measured immunohistochemically. RESULTS: Elevated EGFR copy number was found in 38% of cases but no KRAS nonresponse mutations. VEGFR1, TGFBR1, PDGFRA, SSTR5, SSTR2A, and IGF1R exhibited the highest levels of expression in the largest percentages of PETs.Anticancer drugs BMS-754807 (selective for IGF1R/IR), 17-(allylamino)-17-demethoxygeldanamycin (17-AAG, targeting Hsp90), and axitinib  (directed toward VEGFR1-3/PDGFRA-B/KIT) induced growth inhibition of human QGP-1  PET cells with IC50 values (nM) of 273, 723, and 743, respectively. At growth-inhibiting concentrations, BMS-754807 inhibited IGF1R phosphorylation; 17-AAG induced loss of EGFR, IGF1R, and VEGFR2; and axitinib increased p21(CDKN1A) expression without inhibiting VEGFR2 phosphorylation. CONCLUSIONS: Results encourage further research into multidrug strategies incorporating inhibitors targeting IGF1R or Hsp90 and into studies of axitinib combined with conventional chemotherapeutics toxic to tumor cells in persistent growth arrest.

 

----------------------------------------------------

[82]

TÍTULO / TITLE:  - VEGFR-2, CXCR-2 and PAR-1 germline polymorphisms as predictors of survival in pancreatic carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Oncol. 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mds634

AUTORES / AUTHORS:  - Uzunoglu FG; Kolbe J; Wikman H; Gungor C; Bohn BA; Nentwich MF; Reeh M; Konig AM; Bockhorn M; Kutup A; Mann O; Izbicki JR; Vashist YK

INSTITUCIÓN / INSTITUTION:  - Department of General, Visceral and Thoracic Surgery;

RESUMEN / SUMMARY:  - BackgroundHypoxic environment of pancreatic cancer (PC) implicates high vascular  in-growth, which may be influenced by angiogenesis-related germline polymorphisms. Our purpose was to evaluate polymorphisms of vascular endothelial  growth factor receptor 2 (VEGFR-2), CXC chemokine receptor 2 (CXCR-2), proteinase-activated receptor 1 (PAR-1) and endostatin (ES) as prognostic markers for disease-free (DFS) and overall survival (OS) in PC.Patients and methodsGenotyping of 173 patients, surgically treated for PC between 2004 and 2011, was carried out by TaqMan(®) genotyping assays or polymerase chain reaction. Chi-square test, Kaplan-Meier estimator and Cox regression hazard model were used to assess the prognostic value of selected polymorphisms.ResultsVEGFR-2 -906 T/T and PAR-1 -506 Del/Del genotypes predicted longer DFS (P = 0.003, P = 0.014) and OS (VEGFR-2 -906, P = 0.011). CXCR-2 +1208 T/T genotype was a negative predictor for DFS (P < 0.0001). Combined analysis for DFS and OS indicated that patients with the fewest number of favorable genotypes simultaneously present (VEGFR-2 -906 T/T, CXCR-2 +1208 C/T or C/C and PAR-1 -506 Del/Del) were at the highest risk for recurrence or death (P < 0.0001).ConclusionVEGFR-2 -906 C>T, CXCR-2 +1208 C>T and PAR-1 -506 Ins/Del polymorphisms are potential predictors for survival in PC.

 

----------------------------------------------------

[83]

TÍTULO / TITLE:  - Comparison of uncovered and covered stents for the treatment of malignant duodenal obstruction caused by pancreaticobiliary cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Endosc. 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00464-012-2705-6

AUTORES / AUTHORS:  - Woo SM; Kim DH; Lee WJ; Park KW; Park SJ; Han SS; Kim TH; Koh YH; Kim HB; Hong EK

INSTITUCIÓN / INSTITUTION:  - Center for Liver Cancer, National Cancer Center, 111 Junbalsan-ro, Ilsandong-gu,  Goyang, Gyeonggi, 410-769, South Korea, wsm@ncc.re.kr.

RESUMEN / SUMMARY:  - BACKGROUND: Few clinical studies to date have compared different types of self-expandable metallic stents (SEMS) and their outcomes in patients with pure duodenal obstruction caused by pancreaticobiliary cancer. The aim of this study was to compare the clinical effectiveness and side effects of uncovered and covered SEMS for the palliation of duodenal obstruction caused by pancreaticobiliary cancer. METHODS: We retrospectively analyzed all patients with pancreaticobiliary cancer who underwent upper endoscopy with SEMS placement for malignant duodenal obstruction at the National Cancer Center of Korea between April 2003 and December 2010. The technical and clinical success rates of the procedure, complications, and durations of stent patency and overall survival were evaluated. RESULTS: We identified 70 patients with a mean age of 51.2 years  (range = 39-81 years); of these, 46 (65.7 %) had pancreatic cancer, 9 (12.9 %) had bile duct cancer, 11 (15.7 %) had gallbladder cancer, and 4 (5.7 %) had cancer of the ampulla of Vater. Twenty-four patients (34.3 %) received covered SEMSs and 46 (65.7 %) received uncovered SEMSs. Technical and clinical success rates were similar for the covered and uncovered stent groups. The complication rate was higher in the covered than in the uncovered group (62.5 vs. 34.8 %, P =  0.025), due primarily to a significantly higher stent migration rate (20.8 vs. 0  %, P = 0.004). Perforation as a late complication occurred in four patients, two  in each group (8.3 vs. 4.3 %, P = 0.425). Stent patency tended to be shorter for  covered than for uncovered duodenal stents (13.7 +/- 8.6 weeks vs. not reached, P = 0.069). CONCLUSIONS: The use of uncovered stents may be a preferred option for  duodenal obstruction secondary to pancreaticobiliary malignancies, since they were effective in preventing stent migration and tended to have longer patency than covered stents. Careful attention should be paid to signs and symptoms of perforation during follow-up.

 

----------------------------------------------------

[84]

TÍTULO / TITLE:  - Diabetes mellitus does not impact on clinically relevant pancreatic fistula after partial pancreatic resection for ductal adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surgery. 2012 Dec 28. pii: S0039-6060(12)00633-2. doi: 10.1016/j.surg.2012.10.015.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2012.10.015

AUTORES / AUTHORS:  - Malleo G; Mazzarella F; Malpaga A; Marchegiani G; Salvia R; Bassi C; Butturini G

INSTITUCIÓN / INSTITUTION:  - Unit of General Surgery B, Pancreas Institute, G.B. Rossi Hospital, Department of Surgery, University of Verona Hospital Trust, Verona, Italy.

RESUMEN / SUMMARY:  - BACKGROUND: The prevalence of diabetes mellitus (DM) in patients with pancreatic  ductal adenocarcinoma (PDAC) ranges from 20 to 80%. In patients undergoing resection, it is unclear whether DM impacts on clinically relevant pancreatic fistula (CR-PF). METHODS: To address this issue, data from 602 consecutive partial pancreatic resections were analyzed using univariate and multivariate models. RESULTS: There were 120 patients with DM; 84 had longstanding DM and 36 a new-onset DM. The incidence of CR-PF was greater among nondiabetics (11.8% vs 5.0%; P = .043), who were also more likely to have a soft pancreatic texture (79.5% vs 46.0%; P = .001) or combined presence of soft texture and small pancreatic duct (high-risk pancreas; P = .001). All these variables did not differ when stratifying by DM type. Univariate analysis showed that gender (P = .005), body mass index (P = .05), DM (P = .043), pancreatic texture (P = .001), pancreatic duct size (P = .012), and the combined presence of soft parenchyma and small duct (P = .001) were associated with CR-PF. On multivariate analysis, DM resulted to be a negative predictor of CR-PF (odds ratio [OR], 0.53; P = .047). Additional variables associated with an increased probability of CR-PF formation  were male gender (OR, 3.48; P = .002), soft pancreatic texture (OR, 2.19), pancreatic duct size <3 mm (OR, 1.79), and the combined presence of soft pancreas and small duct (OR, 2.24). CONCLUSION: DM is not a risk factor for CR-PF after resection of PDAC. The decreased incidence of CR-PF in diabetics is likely to be  a consequence of a decreased frequency of high-risk features of the pancreatic gland (soft texture and/or small duct).

 

----------------------------------------------------

[85]

TÍTULO / TITLE:  - MUC5AC protects pancreatic cancer cells from TRAIL-induced death pathways.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar;42(3):887-93. doi: 10.3892/ijo.2013.1760. Epub 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1760

AUTORES / AUTHORS:  - Hoshi H; Sawada T; Uchida M; Iijima H; Kimura K; Hirakawa K; Wanibuchi H

INSTITUCIÓN / INSTITUTION:  - Biomedical Research Laboratories, Kureha Corporation, Shinjuku-ku, Tokyo 169-8503, Japan.

RESUMEN / SUMMARY:  - We have previously reported that a specific siRNA transfected MUC5AC could knockdown MUC5AC expression and suppress in vivo tumor growth and metastasis, although it had no effects on in vitro cell growth, cell survival, proliferation  and morphology. In the present study, we investigated which host immune cells induced these effects and how the effects were induced using immunocyte-depleted  animal models. The tumor growth of SW1990/si-MUC5AC cells, which show no tumor growth when implanted subcutaneously into a nude mouse, was recovered when neutrophils were removed by anti-Gr-1 mAb administration. This result suggests that MUC5AC may suppress the antitumor effects of neutrophils by allowing tumor cells to escape the host immune system. Subsequently, we investigated the effects of MUC5AC on apoptosis induction mediated by TNF-related apoptosis-inducing ligand (TRAIL), one of the antitumor mechanisms of neutrophils. SW1990/si-MUC5AC  cells showed significantly increased active caspase 3 expression after the addition of TRAIL. On the other hand, SW1990/si-mock cells showed no such changes. Our results indicate that MUC5AC inhibits TRAILinduced apoptosis in human pancreatic cancer and may serve as an important indicator in diagnosis and  prognosis.

 

----------------------------------------------------

[86]

TÍTULO / TITLE:  - Highly lymphatic metastatic pancreatic cancer cells possess stem cell-like properties.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar;42(3):979-84. doi: 10.3892/ijo.2013.1780. Epub 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1780

AUTORES / AUTHORS:  - Luo G; Long J; Cui X; Xiao Z; Liu Z; Shi S; Liu L; Liu C; Xu J; Li M; Yu X

INSTITUCIÓN / INSTITUTION:  - Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, P.R.  China.

RESUMEN / SUMMARY:  - Cancer stem cells are thought to be the origin of tumor metastasis. However, evidence of cancer stem cells as the source of lymphatic metastasis in pancreatic cancer is not clear. In this study, we examined the stem cell-like properties of  the highly lymphatic metastatic pancreatic cancer cells BxPC-3-LN. Compared with  the parental BxPC-3 cells, the BxPC-3-LN cells showed stem cell-like properties,  including high lymphatic metastasis potential, self-renewal ability and chemoresistance. In addition, the BxPC-3-LN cells also expressed higher levels of sonic hedgehog and migrating cancer stem cell surface markers (CD133 and CXCR4) compared to the parental BxPC-3 cells. The growth of BxPC-3-LN cells was significantly inhibited by gemcitabine combined with the sonic hedgehog inhibitor cyclopamine. The BxPC-3-LN cells expressed lower levels of let-7, miR-34, miR-107, miR-125, miR-128, miR-130, miR-132 and miR-141 than the parental BxPC-3  cells detected by microRNA PCR array, which were reported to have close relation  to stem cell factors. This study provides evidence that cancer stem cells are the major sources of pancreatic cancer lymphatic metastasis, and microRNAs may regulate lymphatic metastasis in pancreatic cancer through modulating cancer stem cells.

 

----------------------------------------------------

[87]

TÍTULO / TITLE:  - Ectopic expression of the heterotrimeric G15 protein in pancreatic carcinoma and  its potential in cancer signal transduction.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Signal. 2013 Mar;25(3):651-9. doi: 10.1016/j.cellsig.2012.11.018. Epub 2012  Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cellsig.2012.11.018

AUTORES / AUTHORS:  - Giovinazzo F; Malpeli G; Zanini S; Parenti M; Piemonti L; Colombatti M; Valenti MT; Dalle Carbonare L; Scarpa A; Sinnett-Smith J; Rozengurt E; Bassi C; Innamorati G

INSTITUCIÓN / INSTITUTION:  - Laboratory of Translational Surgery, University Laboratories of Medical Research  (LURM), University of Verona, 37134 Verona, Italy; Department of Surgery, University of Verona, 37134 Verona, Italy.

RESUMEN / SUMMARY:  - G15 is a heterotrimeric G protein selectively expressed in immature cell lineages in adult tissues that feature higher cell renewal potential. It promiscuously couples a wide variety of G protein-coupled receptors (GPCRs) to phospholipase C. Intriguingly, G15 is poorly affected by GPCR desensitization. We show here that G15 alpha-subunit (Galpha15) supports sustained stimulation of PKD1 by a constitutively desensitized GPCR co-transfected over a negative cell background.  Based on the fact that PKD1 is a multifunctional protein kinase activated by PKC  and known for promoting oncogenic signaling, we hypothesized that, if expressed out of its natural cell context, G15 might promote tumor growth. A screening for  Galpha15 mRNA expression pointed to pancreatic carcinoma among different human cancer cell types and revealed significant expression in human tumor biopsies xenografted in mice. In addition, G15 ectopic presence could functionally contribute to the transformation process since siRNA-induced depletion of Galpha15 in pancreatic carcinoma cell lines dramatically inhibited anchorage-independent growth and resistance to the lack of nutrients. Altogether, our findings suggest that G15 supports tumorigenic signaling in pancreas and hence it may be considered as a novel potential target for the therapy of this form of cancer.

 

----------------------------------------------------

[88]

TÍTULO / TITLE:  - Non-operative treatment versus percutaneous drainage of pancreatic pseudocysts in children.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Surg Int. 2012 Dec 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00383-012-3236-x

AUTORES / AUTHORS:  - Russell KW; Barnhart DC; Madden J; Leeflang E; Jackson WD; Feola GP; Meyers RL; Scaife ER; Rollins MD

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University of Utah, Salt Lake City, UT, 84113, USA, Katie.Russell@hsc.utah.edu.

RESUMEN / SUMMARY:  - PURPOSE: The objective of this study was to characterize the clinical course and  outcomes of children with pancreatic pseudocysts that were initially treated non-operatively or with percutaneous drainage. METHODS: A retrospective review of children with pancreatic pseudocysts over a 12-year period was completed. Categorical variables were compared using Fischer’s exact method and the Student’s t test was used to compare continuous variables. Analysis was done using logistic and linear regression models. RESULTS: Thirty-six children met the criteria for pancreatic pseudocyst and 33 children were treated either non-operatively or with percutaneous drainage. Of the 22 children managed non-operatively, 17 required no additional intervention (77 %) and five required  surgery. Operative procedures were: Frey procedure (3), distal pancreatectomy (1), and cystgastrostomy (1). Eight of the 11 children treated with initial percutaneous drainage required no additional treatment (72 %). The other three children underwent distal pancreatectomy. Success of non-operative management or  percutaneous drainage was not dependent on size or complexity of the pseudocyst Logistic regression did not identify any patient demographic (gender, age, and weight), etiologic (trauma, non-traumatic pancreatitis) or pseudocyst characteristic (size, septations) that predicted failure of non-operative therapy. CONCLUSIONS: In children, pancreatic pseudocysts can frequently be managed without surgery regardless of size or complexity of the pseudocyst. When  an intervention is needed, percutaneous drainage can be performed successfully, avoiding the need for major surgical intervention in the majority of patients.

 

----------------------------------------------------

[89]

TÍTULO / TITLE:  - Lack of replication of seven pancreatic cancer susceptibility lociidentified in two Asian populations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Epidemiol Biomarkers Prev. 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1055-9965.EPI-12-1182

AUTORES / AUTHORS:  - Campa D; Rizzato C; Bauer AS; Werner J; Capurso G; Costello E; Talar-Wojnarowska R; Jamroziak K; Pezzilli R; Gazouli M; Khaw KT; Key TJ; Bambi F; Mohelnikova-Duchonova B; Heller A; Landi S; Vodickova L; Theodoropoulos G; Bugert P; Vodicka P; Hoheisel J; Delle Fave G; Neoptolemos J; Soucek P; Buchler MW; Giese NA; Canzian F

INSTITUCIÓN / INSTITUTION:  - 1Genomic epidemiology, DKFZ.

RESUMEN / SUMMARY:  - BACKGROUND: Two recent genome-wide association studies (GWAS) of pancreatic ductal adenocarcinoma (PDAC), conducted respectively in a Japanese and in a Chinese population, identified eight novel loci affecting PDAC risk. METHODS: We  attempted to replicate the novel loci in a series of PDAC and healthy controls of European ancestry in the context of the newly formed PANcreatic Disease ReseArch  (PANDoRA) consortium. We genotyped seven single nucleotide polymorphisms (SNPs):  rs12413624, rs1547374, rs372883, rs5768709, rs6464375, rs708224, rs9502893 (one SNP identified in the Chinese GWAS is not polymorphic in Caucasians) in 1299 PDAC cases and 2884 controls. We also attempted stratified analysis considering the different stages of the disease and addressed the possible involvement of the selected SNPs on the survival of patients. RESULTS: None of the SNPs were significantly associated with PDAC risk if considering the overall population of  the consortium. When stratifying for country of origin we found that in the Polish subgroup the G allele of rs372883 was statistically significantly associated with increased risk (OR=6.40; CI 95% 2.28-17.91). However the sample size of the subgroups was rather small, therefore this result can be due to chance. None of the SNPs was associated with disease progression or survival. Conclusions and Impact: None of the SNPs associated with PDAC risk in two Asian populations were convincingly associated with PDAC risk in individuals of European descent. This study illustrates the importance of evaluation of PDAC risk markers across ethnic groups.

 

----------------------------------------------------

[90]

TÍTULO / TITLE:  - Types of Fish Consumed and Fish Preparation Methods in Relation to Pancreatic Cancer Incidence: The VITAL Cohort Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Epidemiol. 2013 Jan 15;177(2):152-60. doi: 10.1093/aje/kws232. Epub 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1093/aje/kws232

AUTORES / AUTHORS:  - He K; Xun P; Brasky TM; Gammon MD; Stevens J; White E

RESUMEN / SUMMARY:  - The associations of types of fish and fish preparation methods with pancreatic cancer risk remain unknown. The authors conducted a prospective cohort study in western Washington State among 66,616 adults, aged 50-76 years, who participated  in the VITamins And Lifestyle cohort study. Diet was assessed by a food frequency questionnaire. Pancreatic cancer cases were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. During an average follow-up of 6.8 years, 151 participants developed pancreatic cancer (adenocarcinoma). Long-chain (n-3) polyunsaturated fatty acids (LC-PUFAs) and nonfried fish intake were inversely associated with pancreatic cancer incidence.  When the highest and lowest tertiles of exposure were compared, the multivariable-adjusted hazard ratio of pancreatic cancer was 0.62 (95% confidence interval: 0.40, 0.98) (P(trend) = 0.08) for LC-PUFAs and 0.55 (95% confidence interval: 0.34, 0.88) (P(trend) = 0.045) for nonfried fish. Docosahexaenoic acid  showed a greater inverse association with pancreatic cancer than eicosapentaenoic acid. No statistically significant associations were observed with fried fish and shellfish consumption. The potential health impact of fish consumption may depend on the types of fish consumed and fish preparation methods. LC-PUFAs, particularly docosahexaenoic acid, and nonfried fish, but not shellfish or fried  fish, may be beneficial in the primary prevention of pancreatic cancer.

 

----------------------------------------------------

[91]

TÍTULO / TITLE:  - Treatment of unresectable pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AJR Am J Roentgenol. 2013 Feb;200(2):467. doi: 10.2214/AJR.12.9353.

            ●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.9353

AUTORES / AUTHORS:  - Hall FM

INSTITUCIÓN / INSTITUTION:  - Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

 

----------------------------------------------------

[92]

TÍTULO / TITLE:  - Mutations in K-Ras linked to levels of osteoprotegerin and sensitivity to TRAIL-induced cell death in pancreatic ductal adenocarcinoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Mol Pathol. 2012 Dec 5. pii: S0014-4800(12)00174-8. doi: 10.1016/j.yexmp.2012.11.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.yexmp.2012.11.003

AUTORES / AUTHORS:  - Kanzaki H; Ohtaki A; Merchant FK; Greene MI; Murali R

INSTITUCIÓN / INSTITUTION:  - Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA.

RESUMEN / SUMMARY:  - Osteoprotegerin (OPG) is a soluble receptor expressed in the serum of patients with diabetes, arthritis and pancreatic cancer. While OPG has been considered a tumor survival factor for bone metastasizing breast and prostate cancers, the role of OPG in pancreatic cancer, which itself rarely metastasizes to bone, is not known. Pancreatic ductal adenocarcinoma (PDAC) cell lines were found to secrete OPG and the level of OPG production correlated with sensitivity to TRAIL-induced apoptosis. Silencing OPG sensitized cells to TRAIL-induced apoptosis. Interestingly, a positive correlation was noted between OPG production level and K-Ras mutation status. Earlier studies implicated K-Ras in conferring resistance to TRAIL-induced apoptosis in pancreatic cells and this study demonstrates that K-Ras mediated TRAIL resistance in pancreatic cancer cells occurs due to increased OPG production. Silencing K-Ras in pancreatic cancer cells decreased OPG levels and increased sensitivity to TRAIL-induced apoptosis.  These observations indicate that OPG can play a role in both cell survival and in PDAC cell sensitivity to TRAIL-induced apoptosis, which may contribute to metastasis. Targeted inhibition of OPG binding to TRAIL may represent a therapeutic approach in the treatment of pancreatic cancer.

 

----------------------------------------------------

[93]

TÍTULO / TITLE:  - Islet-1 Is a Sensitive But Not Entirely Specific Marker for Pancreatic Neuroendocrine Neoplasms and Their Metastases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Surg Pathol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e31826f042c

AUTORES / AUTHORS:  - Graham RP; Shrestha B; Caron BL; Smyrk TC; Grogg KL; Lloyd RV; Zhang L

INSTITUCIÓN / INSTITUTION:  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

RESUMEN / SUMMARY:  - Islet-1 (Isl1) is a transcription factor involved in the embryogenesis of islets  of Langerhans. Immunohistochemically, Isl1 is a sensitive lineage-specific marker for pancreatic neuroendocrine neoplasms (NENs) and their metastases. Its specificity has not been documented, nor have large numbers of NENs from other parts of the gut or other organs been studied. We examined Isl1 expression in 203 primary NENs (gastroenteropancreatic, lung, breast, and ovarian neoplasms) and 40 hepatic NEN metastases (enteropancreatic and lung neoplasms) from known primaries. The correlation between Isl1 and CDX2 expression was studied using a tissue microarray containing 46 pancreatic NENs. Immunostaining for Isl1 and CDX2 was also performed in selected NENs from other sites. Isl1 was positive in 90% of pancreatic, 89% of duodenal, 100% of rectal, 38% of colonic, 14% of appendiceal,  and 6% of ileal primaries. Isl1 was negative in all other NENs. Among metastatic  neoplasms, 76% of pancreatic and 2 of 2 rectal NEN metastases were Isl1 positive, whereas all other tested metastases were negative. The overall sensitivity and specificity of Isl1 in identifying primary pancreatic NENs was 88% and 80%, respectively. Thirty-six of 46 pancreatic NENs in the tissue microarray were Isl1 positive; 4 were Isl1 negative but CDX2 positive. Our findings confirm that Isl1  is a sensitive marker of pancreatic origin in cases of metastatic NEN. However, Isl1 does not distinguish pancreatic NEN from duodenal and colorectal NEN, even when used in association with CDX2.

 

----------------------------------------------------

[94]

TÍTULO / TITLE:  - Staging and treatment response evaluation in a metastatic neuroendocrine tumor of the pancreas with G2 grading: insights from multimodality diagnostic approach by  F-18-FDG and Ga-68-DOTANOC PET/CT.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocrine. 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12020-012-9858-x

AUTORES / AUTHORS:  - Treglia G; Plastino F; Campitiello M

INSTITUCIÓN / INSTITUTION:  - Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Largo A.  Gemelli 8, 00168, Rome, Italy, giorgiomednuc@libero.it.

 

----------------------------------------------------

[95]

TÍTULO / TITLE:  - Re-resection for Isolated Local Recurrence of Pancreatic Cancer is Feasible, Safe, and Associated with Encouraging Survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2762-z

AUTORES / AUTHORS:  - Strobel O; Hartwig W; Hackert T; Hinz U; Berens V; Grenacher L; Bergmann F; Debus J; Jager D; Buchler M; Werner J

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.

RESUMEN / SUMMARY:  - BACKGROUND: Local recurrence of pancreatic cancer occurs in 80 % of patients within 2 years after potentially curative resections. Around 30 % of patients have isolated local recurrence (ILR) without evidence of metastases. In spite of  localized disease these patients usually only receive palliative chemotherapy and have a short survival. PURPOSE: To evaluate the outcome of surgery as part of a multimodal treatment for ILR of pancreatic cancer. METHODS: All consecutive operations performed for suspected ILR in our institution between October 2001 and October 2009 were identified from a prospective database. Perioperative outcome, survival, and prognostic parameters were assessed. RESULTS: Of 97 patients with histologically proven recurrence, 57 (59 %) had ILR. In 40 (41 %) patients surgical exploration revealed metastases distant to the local recurrence. Resection was performed in 41 (72 %) patients with ILR, while 16 (28  %) ILR were locally unresectable. Morbidity and mortality were 25 and 1.8 % after resections and 10 and 0 % after explorations, respectively. Median postoperative  survival was 16.4 months in ILR versus 9.4 months in metastatic disease (p < 0.0001). In ILR median survival was significantly longer after resection (26.0 months) compared with exploration without resection (10.8 months, p = 0.0104). R0 resection was achieved in 18 patients and resulted in 30.5 months median survival. Presence of metastases, incomplete resection, and high preoperative CA  19-9 serum values were associated with lesser survival. CONCLUSIONS: Resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with favorable survival outcome. This concept warrants further evaluation in other institutions and in randomized controlled trials.

 

----------------------------------------------------

[96]

TÍTULO / TITLE:  - Double inhibition of NF-kappaB and XIAP via RNAi enhances the sensitivity of pancreatic cancer cells to gemcitabine.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Jan 23. doi: 10.3892/or.2013.2246.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2246

AUTORES / AUTHORS:  - Cao LP; Song JL; Yi XP; Li YX

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, Xiangya Hospital, Central South University, Hunan  410008, P.R. China.

RESUMEN / SUMMARY:  - The majority of patients with pancreatic cancer are resistant to gemcitabine. One of the mechanisms involved is the anti-apoptotic ability of these cells. The median lethal dose (LD50) of gemcitabine for PANC-1 cells was higher than that for Mia PaCa-2 cells and the former had higher nuclear factor-kappaB (NF-kappaB)  and X-linked inhibitor of apoptosis protein (XIAP) levels. NF-kappaB contributes  to the inhibition of apoptosis by the downregulation of downstream genes, such as XIAP and Bcl-2 and it confers chemoresistance. The two cell lines were infected with NF-kappaB p65 small interfering RNA (siRNA). p65 protein was effectively downregulated accompanied by the downregulation of XIAP protein. The combination  treatment with gemcitabine and p65 siRNA increased the apoptotic rates in both cell lines; however, this was not sufficient. XIAP is involved in apoptosis to a  greater extent compated to Bcl-2. XIAP may serve as another factor affecting the  sufficiency of chemotherapy. XIAP siRNA was designed to knockdown XIAP. Mia PaCa-2 and PANC-1 cells were co-infected with XIAP siRNA and p65 siRNA. XIAP and  p65 proteins were effectively downregulated and the gemcitabine-induced apoptotic rates were significantly increased. These results suggest that XIAP and NF-kappaB are two important factors conferring the chemoresistance of pancreatic cancer cells, and that their downregulation via RNAi effectively enhances the chemosensitivity of pancreatic cancer cells to gemcitabine.

 

----------------------------------------------------

[97]

TÍTULO / TITLE:  - Synergistic anticancer activity of HS-173, a novel PI3K inhibitor in combination  with Sorafenib against pancreatic cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Jan 20. pii: S0304-3835(13)00029-3. doi: 10.1016/j.canlet.2013.01.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.007

AUTORES / AUTHORS:  - Yun SM; Jung KH; Lee H; Son MK; Seo JH; Yan HH; Park BH; Hong S; Hong SS

INSTITUCIÓN / INSTITUTION:  - College of Medicine, Inha University, 3-ga, Sinheung-dong, Jung-gu, Incheon 400-712, Republic of Korea.

RESUMEN / SUMMARY:  - The RAF/MEK/ERK and PI3K/AKT pathways are highly implicated in the development of pancreatic cancer. The principal objective of this study was to assess the synergic effect between Sorafenib (a RAF inhibitor) and HS-173 (a novel PI3K inhibitor) to gain insight into novel therapeutic strategies for treating pancreatic cancer. We first investigated the cytotoxic effect of co-treatment with Sorafenib and HS-173 using the Calcusyn program. Combined treatment of the two drugs synergistically inhibited the viability of Panc-1 cells (combination index<1). Concomitantly, the co-treatment induced G2/M arrest and increased apoptosis with the loss of mitochondrial membrane potential. Apoptosis resulting  from the co-treatment was accompanied by increased levels of cleaved caspase-3 and PARP as well as greater numbers of TUNEL-positive apoptotic cells compared to treatment with either drug alone. Furthermore, combined treatment with these drugs decreased the expression of HIF-1alpha and VEGF which play an important role in angiogenesis. This anti-angiogenic effect was confirmed by the suppressed tube formation of VEGF-induced human umbilical vein endothelial cells and inhibition of blood vessel formation in a Matrigel plug assay in mice. Taken together, our study demonstrates that combined treatment with Sorafenib and HS-173 has a synergistic anti-cancer effect on pancreatic cancer cells, indicating that simultaneously targeting the RAF/MEK and PI3K/AKT pathways can induce a synergistic inhibitory effect on pancreatic cancers in which both pathways are activated. Based on the observations from our study, we suggest that the combined administration of these two drugs may be considered to be a new therapeutic regimen for treating pancreatic cancer.

 

----------------------------------------------------

[98]

TÍTULO / TITLE:  - The clinical significance of SWI/SNF complex in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Feb;42(2):403-10. doi: 10.3892/ijo.2012.1723. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2012.1723

AUTORES / AUTHORS:  - Numata M; Morinaga S; Watanabe T; Tamagawa H; Yamamoto N; Shiozawa M; Nakamura Y; Kameda Y; Okawa S; Rino Y; Akaike M; Masuda M; Miyagi Y

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterological Surgery, Kanagawa Cancer Center, Asahi-ku, Yokohama, Kanagawa 241-0815, Japan.

RESUMEN / SUMMARY:  - Chromatin remodeling factors have been the subject of great interest in oncology. However, little is known about their role in pancreatic cancer. The objective of  this study was to clarify the clinical significance of the SWItch/sucrose non-fermentable (SWI/SNF) complex in patients with pancreatic cancer. A total of  68 patients with pancreatic cancer who underwent R0, 1 resection were enrolled. Cancer tissues were processed to tissue microarray, then stained immunohistochemically by using antibody of SWI/SNF components; BRM, BRG1, BAF250a, BAF180 and BAF47. The correlation of expression levels and clinicopathological outcomes were analyzed, followed by the multivariate analysis of prognostic factors for overall survival. The expression levels of the SWI/SNF  components were categorized as low or high according to the median value of Histoscore. Statistical analysis revealed that BRM expression was related to tumor size, T factor, M factor, lymphatic invasion and stage BRG1 expression to histology and stage BAF180 expression to tumor size and BAF47 expression to lymphatic invasion, respectively. Multivariate Cox proportional hazard analysis showed that high BRM and low BAF180 expression levels were independent predictors of worse survival in patients with pancreatic cancer. High BRM, and low BAF180 were also independent prognostic factors for poor survival in the subgroup with adjuvant gemcitabine. These results suggest that the specific cofactors of SWI/SNF chromatin remodeling complex certainly have roles in pancreatic cancer. High BRM, and low BAF180 are useful biomarkers for poor prognosis in pancreatic cancer.

 

----------------------------------------------------

[99]

TÍTULO / TITLE:  - Autophagy induced by p53-reactivating molecules protects pancreatic cancer cells  from apoptosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Apoptosis. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10495-012-0790-6

AUTORES / AUTHORS:  - Fiorini C; Menegazzi M; Padroni C; Dando I; Dalla Pozza E; Gregorelli A; Costanzo C; Palmieri M; Donadelli M

INSTITUCIÓN / INSTITUTION:  - Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Strada Le Grazie 8, 37134, Verona, Italy.

RESUMEN / SUMMARY:  - TP53 mutations compromising p53 transcriptional function occur in more than 50 %  of human cancers, including pancreatic adenocarcinoma, and render cancer cells more resistant to conventional therapy. In the last few years, many efforts have  been addressed to identify p53-reactivating molecules able to restore the wild-type transcriptionally competent conformation of the mutated proteins. Here, we show that two of these compounds, CP-31398 and RITA, induce cell growth inhibition, apoptosis, and autophagy by activating p53/DNA binding and p53 phosphorylation (Ser15), without affecting the total p53 amount. These effects occur in both wild-type and mutant p53 pancreatic adenocarcinoma cell lines, whereas they are much less pronounced in normal human primary fibroblasts. Furthermore, CP-31398 and RITA regulate the axis SESN1-2/AMPK/mTOR by inducing AMPK phosphorylation on Thr172, which has a crucial role in the autophagic response. The protective role of autophagy in cell growth inhibition by CP-31398  and RITA is supported by the finding that the AMPK inhibitor compound C or the autophagy inhibitors chloroquine or 3-methyladenine sensitize both pancreatic adenocarcinoma cell lines to the apoptotic response induced by p53-reactivating molecules. Our results demonstrate for the first time a survival role for autophagy induced by p53-reactivating molecules, supporting the development of an anti-cancer therapy based on autophagy inhibition associated to p53 activation.

 

----------------------------------------------------

[100]

TÍTULO / TITLE:  - A small-molecule induces apoptosis and suppresses metastasis in pancreatic cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Pharm Sci. 2013 Jan 10. pii: S0928-0987(13)00002-X. doi: 10.1016/j.ejps.2012.12.023.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejps.2012.12.023

AUTORES / AUTHORS:  - Li D; Liu Z; Zhao W; Zheng X; Wang J; Wang E

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China.

RESUMEN / SUMMARY:  - Pancreatic cancer is one of the most malignant tumor diseases with the characters of aggressive growth and metastasis. With the inefficiency of the current therapeutics, new potential targets and new therapeutic agents for healing of pancreatic cancer are critically needed. We have previously found a small molecule, named 4-tert-butyl-2-[(cyclohexylamino) methyl]-6-methylphenol (TBMMP,  NSC number: 48160), which can freeze the intermediate of Ras-GTP hydrolysis in the open non-signaling conformation with high affinity and high specificity in silico. In this work, we studied the effect and mechanism of TBMMP on two pancreatic cancer cell lines, CFPAC-1 and BxPC-3. The results showed that TBMMP could restrain the growth of the pancreatic cancer cells with IC(50) value 84.3muM for CPFAC-1 and 94.5muM for BxPC-3, respectively. Additionally, TBMMP increased cytochrome c release, reduced mitochondrial membrane potential, activated caspase-3, -9, elevated ROS and increased expression of the Bax in the  pancreatic cancer cell lines. Collectively, the results indicated that TBMMP induced the apoptosis of pancreatic cancer cells through the mitochondrial pathway. Further, we also found that TBMMP could suppress the metastasis of both  pancreatic cancer cells in vitro. Taken together, we proposed that TBMMP might be a therapeutic potential lead for treating patients with pancreatic cancer.

 

----------------------------------------------------

[101]

TÍTULO / TITLE:  - Nutrient-based dietary patterns and pancreatic cancer risk.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Epidemiol. 2013 Jan 16. pii: S1047-2797(12)00457-7. doi: 10.1016/j.annepidem.2012.12.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.annepidem.2012.12.005

AUTORES / AUTHORS:  - Bosetti C; Bravi F; Turati F; Edefonti V; Polesel J; Decarli A; Negri E; Talamini R; Franceschi S; La Vecchia C; Zeegers MP

INSTITUCIÓN / INSTITUTION:  - Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy. Electronic address: cristina.bosetti@marionegri.it.

RESUMEN / SUMMARY:  - PURPOSE: Few data are available on the role of combinations of foods and/or nutrients on pancreatic cancer risk. To add further information on dietary patterns potentially associated to pancreatic cancer, we applied an exploratory principal component factor analysis on 28 major nutrients derived from an Italian case-control study. METHODS: Cases were 326 incident pancreatic cancer cases and  controls 652 frequency-matched controls admitted to hospital for non-neoplastic diseases. Dietary information was collected through a validated and reproducible  food frequency questionnaire. Multiple logistic regression models adjusted for sociodemographic variables and major recognized risk factors for pancreatic cancer were used to estimate the odds ratios (OR) of pancreatic cancer for each dietary pattern. RESULTS: We identified four dietary patterns-named “animal products,” “unsaturated fats,” “vitamins and fiber,” and “starch rich,” that explain 75% of the total variance in nutrient intake in this population. After allowing for all the four patterns, positive associations were found for the animal products and the starch rich patterns, the OR for the highest versus the lowest quartiles being 2.03 (95% confidence interval [CI], 1.29-3.19) and 1.69 (95% CI, 1.02-2.79), respectively; an inverse association emerged for the vitamins and fiber pattern (OR, 0.55; 95% CI, 0.35-0.86), whereas no association  was observed for the unsaturated fats pattern (OR, 1.13; 95% CI, 0.71-1.78). CONCLUSIONS: A diet characterized by a high consumption of meat and other animal  products, as well as of (refined) cereals and sugars, is positively associated with pancreatic cancer risk, whereas a diet rich in fruit and vegetables is inversely associated.

 

----------------------------------------------------

[102]

TÍTULO / TITLE:  - Endosonography-guided transmural drainage of pancreatic pseudocysts using an exchange-free access device: initial clinical experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Endosc. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00464-012-2682-9

AUTORES / AUTHORS:  - Binmoeller KF; Weilert F; Shah JN; Bhat YM; Kane S

INSTITUCIÓN / INSTITUTION:  - Paul May and Frank Stein Center for Interventional Endoscopy, California Pacific  Medical Center, San Francisco, CA, USA, kbinmoeller@endovision.com.

RESUMEN / SUMMARY:  - BACKGROUND: Endosonography (EUS)-guided transmural pseudocyst drainage is a multistep procedure currently performed with different “off-the-shelf” accessories developed for other applications. Multiple device exchanges over-the-wire is time consuming and risks loss of wire access. This report describes the technical feasibility and outcomes for EUS-guided drainage of pancreatic fluid collections using a novel exchange-free device developed for translumenal therapy. METHODS: Between April and November 2010, 14 patients (9 men; mean age, 49.9 years) with pancreatic fluid collection (mean size, 102 mm) underwent 16 EUS-guided drainage procedures using the exchange-free access device at a single tertiary care center. The trocar of the exchange-free device was used to gain pseudocyst access. The dual-balloon catheter then was advanced over the trocar, followed by inflation of the (first) anchor balloon. Cyst contents were sampled, and contrast was injected to define the pseudocyst anatomy. The first guidewire was inserted into the cyst cavity. The cystenterostomy tract was dilated to 10 mm with the (second) dilation balloon, followed by a second guidewire insertion. The exchange-free access device was removed, leaving the two guidewires in place for two double-pigtail stents. RESULTS: The procedure was technically successful for all the patients. No acute procedure-related complications occurred. Late complications included a symptomatic leak in a patient who underwent drainage of a pancreatic uncinate pseudocyst from the second duodenum, a self-limited transfusion-dependent bleed after transbulbar drainage, and symptomatic pseudocyst infection. CONCLUSION: Pseudocyst access, cystenterostomy tract dilation, and placement of two guidewires for dual stent drainage are technically feasible using an exchange-free access device. The device has the potential to standardize, simplify, and streamline EUS-guided pseudocyst drainage with a single instrument. Comparative studies with alternative tools and methods for pseudocyst drainage are warranted.

 

----------------------------------------------------

[103]

TÍTULO / TITLE:  - Long-term Analysis of Gemcitabine-based Chemoradiation after Surgical Resection for Pancreatic Adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2767-7

AUTORES / AUTHORS:  - Mattiucci GC; Ippolito E; D’Agostino GR; Alfieri S; Antinori A; Crucitti A; Balducci M; Deodato F; Luzi S; Macchia G; Smaniotto D; Morganti AG; Valentini V

INSTITUCIÓN / INSTITUTION:  - Department of Radiotherapy, Policlinico Universitario “Agostino Gemelli”, Catholic University, Rome, Italy.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the efficacy in terms of local control (LC) of 24 h infusion of gemcitabine plus radiotherapy after surgery for pancreatic cancer. METHODS: Weekly gemcitabine (100 mg/m(2)) was provided as a 24-hour infusion during the course of radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). Patients subsequently received five cycles of gemcitabine monochemotherapy (1,000 mg/m(2)  1, 8, q21). The primary end point of the study was to achieve a 2-year LC rate of >/=80 % with type I and II errors of 5 and 20 %. The study was designed to accrue a maximum sample size of 35 patients. Secondary end points were toxicity evaluation, metastasis-free survival (MFS), and overall survival (OS). RESULTS: Data of 35 patients were available. Most of the patients (n = 27; 77.1 %) had duodeno-cephalo-pancreatectomy, 5 (14.3 %) distal pancreatectomy, and 3 (8.6 %) total pancreatectomy. The pathological stages were T1-T2 (n = 7; 20.0 %), T3-T4 (n = 28; 80.0 %), N0 (n = 17; 48.6 %), and N1 (n = 18; 51.4 %). Thirty patients (85.7 %) completed chemoradiation. Twenty-three patients (65.7 %) received further sequential chemotherapy. Acute toxicity was acceptable. No late toxicity  occurred. The median follow-up period was 64 (range 24-118) months, and 2-year crude rate of LC was 83 (median not reached). Median MFS and OS were 26.5 and 22.5 months, respectively. CONCLUSIONS: The rate of LC met the main goal of the study. The regimen resulted in a high LC rate but failed to show a benefit in terms of OS or MFS, thus suggesting the need for a more intensified multimodal approach.

 

----------------------------------------------------

[104]

TÍTULO / TITLE:  - Downregulation of Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 Enhances the Sensitivity of Human Pancreatic Cancer Cells to Radiotherapy In Vitro.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Biother Radiopharm. 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1266

AUTORES / AUTHORS:  - Chen S; Xiong G; Wu S; Mo J

INSTITUCIÓN / INSTITUTION:  - 1 Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Jiao-Tong University School of Medicine Renji Hospital; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University) , Shanghai, China .

RESUMEN / SUMMARY:  - Abstract Background: Radiotherapy is an important treatment for the patients with advanced pancreatic cancer. Emerging studies determined apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) might associate with the resistance of human pancreatic cancer cells to radiotherapy. Aims: To investigate whether downregulation of APE1/Ref-1 expression by ribonucleic acid interference would increase the sensitivity of chromic-P32 phosphate to pancreatic cancer cells. Methods: The plasmids containing APE-specific and unspecific short hairpin were transfected into Patu-8898 cells. Stable cell clones were selected by G418. The mRNA expression of APE1/Ref-1 was detected by semiquantitative reverse transcription-polymerase chain reaction and the protein expression of APE1/Ref-1  was detected by Western blot analysis; cell proliferation was studied by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and colony formation assay; apoptosis was detected by flow cytometry. Results: After 24 hours irradiation, APE1/Ref-1 mRNA and protein expression were upregulated, in a  concentration-dependent manner. Suppression of APE1/Ref-1 by siRNA increased the  pancreatic cancer cells hypersensitive to (32)P-CP. In the combination of (32)P-CP and siRNA group, MTT assay showed that the cell inhibition increased to  (74.33%+/-9.02%), the surviving fraction in the colony formation assay was only 25.00%, and the apoptosis rate was up to (16.77%+/-0.98%). Conclusions: Knockdown APE1/Ref-1 gene expression may significantly sensitize the Patu-8988 cells to radiotherapy, which may be a useful target for modifying radiation resistance of  pancreatic cancer cells to irradiation.

 

----------------------------------------------------

[105]

TÍTULO / TITLE:  - Etiology and oncogenesis of pancreatic carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Coll Antropol. 2012 Sep;36(3):1063-7.

AUTORES / AUTHORS:  - Dobrila-Dintinjana R; Vanis N; Dintinjana M; Radic M

INSTITUCIÓN / INSTITUTION:  - University of Rijeka, Rijeka University Hospital Center, Department of Radiotherapy and Oncology, Rijeka, Croatia. renatadobrila@windowslive.com

RESUMEN / SUMMARY:  - Pancreatic cancer is the fourth leading cause of cancer death overall. The factors that favor the development of pancreatic cancer can be divided into hereditary and acquired. Cancerogenesis is best explained by a “multi-hit” hypothesis, charcterized with the developmental sequence of cellular mutatitions, forcing mutant cell to inappropriate proliferation and preventing its repair and  programmed cell death (apoptosis). The most common mutations involve K-ras gene,  epidermal growth factor (EGF-R) and HER2 gene. Continuous stimulation and secretion of vascular endothelial growth factor (VEGF) enhances the permeability  of blood vessels provides nutrient supply to tumor site through newly formed vascular channels. This phenomena is known as vasculogenic mimicry. Loss of function of tumor-suppressor genes has been documented in pancreatic cancer, especially in CDKN2a, p53, DPC4 and BRCA2 genes. SDKN2A gene inactivation occurs  in 95% of pancreatic adenocarcinoma. As regards acquired factors, smoking is only confirmed risk factor that increases the risk of pancreatic cancer. Diabetes, alcohol consumption, central obesity in men, infection with Helicobacter pylori and chronic pancreatitis are suspected, but not proven risk factors. Consumption  of fruits and vegetables does not protect, while the consumption of meat processed at high temperatures increases the risk of pancreatic cancer. According to some studies, lykopene and folate levels are reduced in pancreatic carcinoma patients, reduced folate intake increases the risk of pancreatic carcinoma (48%), and this risk can be diminished by introducing folate-rich foods to diet, not by  using pharmaceutical products. Occupational exposure to chlorinated hydrocarbons, vinyl chloride, nickel, chromium, insecticides and acrylic amide minimally increases the risk for pancreatic cancer. Exposure to cadmium (metal industry) associated with smoking result in the accumulation of cadmium in pancreatic tissue and the possible impact on carcinogenesis.

 

----------------------------------------------------

[106]

TÍTULO / TITLE:  - Combined pancreas and liver therapies: Resection and ablation in hepato-pancreatico-biliary malignancies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Surg Oncol. 2013 Jan 17. doi: 10.1002/jso.23318.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jso.23318

AUTORES / AUTHORS:  - Edwards J; Scoggins C; McMasters K; Martin R

INSTITUCIÓN / INSTITUTION:  - Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky.

RESUMEN / SUMMARY:  - BACKGROUND: Combined pancreatic and liver resection for hepato-pancreatico-biliary disease is generally considered contraindicated since  it is thought to provide little if any survival benefit with high risk of morbidity. Our goal was to review our experience with combined pancreatic and liver resections to better define characteristics that increase risk for perioperative complications after combined resections. METHODS: A review of prospectively collected IRB approved hepato-pancreatico-biliary database was performed from October 2002 to April 2012. RESULTS: Twenty-one cases were identified including all histologies. Perioperative outcomes were examined and the overall mean length of stay was 12.1 days (range: 6-26 days) and no perioperative mortalities (<90 days) were observed. With respect to morbidity 43% of patients experienced any grade of complication, 29% were Grade 3 with no Grade 4 or 5 complications noted. We found a statistically indicated association between BMI > 25 and risk of Grade 3 complications (P = 0.149). The median survival following operation was 11 months (range: 3-148 months). CONCLUSION: Combined pancreas and liver resection for metastatic disease should only be considered in highly selected patients. Tumor histology as well as BMI > 25 (overweight and obese patients) should be considered in the decision making process in an effort to minimize surgical morbidity while potentially improving survival. J. Surg. Oncol © 2013 Wiley Periodicals, Inc.

 

----------------------------------------------------

[107]

TÍTULO / TITLE:  - Viral Therapy for Pancreatic Cancer: Tackle the Bad Guys with Poison.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Jan 24. pii: S0304-3835(13)00078-5. doi: 10.1016/j.canlet.2013.01.035.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.035

AUTORES / AUTHORS:  - Xu C; Li H; Su C; Li Z

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Changhai Hospital, Second military medical university, Shanghai 200433, China.

RESUMEN / SUMMARY:  - Pancreatic cancer is one of the most devastating diseases with very poor prognosis. Only a small proportion is curable by surgical resection, whilst standard chemotherapy for patients with advanced disease has only modest effect with substantial toxicity. Therefore, there is an urgent need for the development of novel therapeutic approaches to improve the patient outcome. Recently the viral therapy is emerging as a novel effective therapeutic approach for cancer with the potential to selectively treat both primary tumor and metastatic lesions. This review provides an overview of the current status of viral treatment for pancreatic cancer, both in the laboratories and in clinical settings.

 

----------------------------------------------------

[108]

TÍTULO / TITLE:  - Radical treatment of stage IV pancreatic cancer by the combination of cryosurgery and iodine-125 seed implantation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Gastroenterol. 2012 Dec 21;18(47):7056-62. doi: 10.3748/wjg.v18.i47.7056.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v18.i47.7056

AUTORES / AUTHORS:  - Chen JB; Li JL; He LH; Liu WQ; Yao F; Zeng JY; Zhang Y; Xu KQ; Niu LZ; Zuo JS; Xu KC

INSTITUCIÓN / INSTITUTION:  - Ji-Bing Chen, Jia-Liang Li, Wei-Qun Liu, Fei Yao, Jian-Ying Zeng, Central Lab of  Guangzhou Fuda Cancer Hospital, Guangzhou 510665, Guangdong Province, China.

RESUMEN / SUMMARY:  - AIM: To investigate the therapeutic effect of radical treatment and palliative treatment in stage IV pancreatic cancer patients. METHODS: 81 patients were enrolled in the study. Radical treatment was performed on 51 patients, while 30 patients were put under palliative treatment. The procedural safety and interval  survival for stage IV pancreatic cancer (IS-IV) was assessed by almost 2.5 years  of follow-ups. The IS-IV of patients under the two kinds of treatment, and the effects of treatment timing and frequency on IS-IV, were compared. RESULTS: The IS-IV of patients who received radical treatment was significantly longer than those who received palliative treatment (P < 0.001). The IS-IV of patients who received delayed radical or palliative treatment was longer than those who received accordingly timely treatment (P = 0.0034 and 0.0415, respectively). Multiple treatments can play an important role in improving the IS-IV of patients who received radical treatment (P = 0.0389), but not for those who received palliative treatment (P = 0.99). CONCLUSION: The effect of radical treatment was  significantly more obvious than that of palliative treatment, and multiple radical treatments may contribute more to patients than a single radical treatment.

 

----------------------------------------------------

[109]

TÍTULO / TITLE:  - Evolution of Pancreatic Function during the First Year in Infants with Cystic Fibrosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr. 2012 Dec 11. pii: S0022-3476(12)01155-9. doi: 10.1016/j.jpeds.2012.10.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jpeds.2012.10.008

AUTORES / AUTHORS:  - O’Sullivan BP; Baker D; Leung KG; Reed G; Baker SS; Borowitz D

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, University of Massachusetts Medical School, Worcester,  MA. Electronic address: Brian.O’Sullivan@umassmemorial.org.

RESUMEN / SUMMARY:  - OBJECTIVE: To describe pancreatic function during the first year of life in infants diagnosed with cystic fibrosis (CF) using serial fecal elastase measurements. STUDY DESIGN: This was a longitudinal study of 82 infants diagnosed with CF through newborn screening. Monthly stool samples were sent to a central laboratory for fecal elastase measurements. RESULTS: A total of 61 infants had an initial stool sample obtained at age <3.5 months and a final stool sample obtained at age >9 months. Twenty-six of 29 infants with a fecal elastase value <50 mug/g at study entry had a fecal elastase value <200 mug/g (the accepted cutoff value for pancreatic insufficiency) on all measurements during the year; all 29 had a value <200 mug/g at the end of the study. Of the 48 infants with initial fecal elastase value <200 mug/g, 13 had at least 1 fecal elastase value >200 mug/g but had a final stool fecal elastase value <200 mug/g; however, 4 infants with an initial fecal elastase value <200 mug/g ended the year with a value >200 mug/g. Eleven of 13 infants with an initial fecal elastase value of >200 mug/g still had a value >200 mug/g at the end of the first year. CONCLUSION: Infants with CF exhibit variability in fecal elastase values during the first year. Infants with a fecal elastase level of 50-200 mug/g at diagnosis should be  treated with pancreatic enzyme replacement therapy, but fecal elastase should be  remeasured at age 1 year to ensure that those with a falsely low value do not continue to receive pancreatic enzyme replacement therapy unnecessarily. Those with a fecal elastase value >200 mug/g initially can become pancreatic insufficient with time.

 

----------------------------------------------------

[110]

TÍTULO / TITLE:  - Identification of common variants in BRCA2 and MAP2K4 for susceptibility to sporadic pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt004

AUTORES / AUTHORS:  - Huang L; Wu C; Yu D; Wang C; Che X; Miao X; Zhai K; Chang J; Jiang G; Yang X; Cao G; Hu Z; Zhou Y; Zuo C; Wang C; Zhang X; Zhou Y; Yu X; Dai W; Li Z; Shen H; Liu L; Chen Y; Zhang S; Wang X; Liu Y; Sun M; Cao W; Gao J; Ma Y; Zheng X; Cheung ST; Jia Y; Tan W; Wu T; Lin D

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

RESUMEN / SUMMARY:  - Germline mutations in genes that cause hereditary syndromes are highly predisposed to familial pancreatic cancer. However, genetic susceptibility to sporadic pancreatic cancer is largely uncovered. We conducted a two-stage association study on pancreatic cancer that included 981 cases and 1991 controls  in the first stage followed by a second stage (2603 cases and 2877 controls). Using an approach based on candidate genes whose roles in pancreatic cancer have  been well known, we identified two new susceptibility loci. rs11571836 located in the BRCA2 3’-untranslated region was significantly associated with lower expression of BRCA2 transcript and increased pancreatic cancer risk [odds ratio = 1.30, 95% confidence interval = 1.14-1.47, P = 7.64 x 10(-5)] in a recessive manner. rs12939944 located in the MAP2K4 intron was associated with decreased risk (odds ratio = 0.82, 95% confidence interval = 0.74-0.91, P = 0.0001) in a dominant manner. Our results demonstrate for the first time that common variants  in BRCA2 and MAP2K4 are susceptibility to sporadic pancreatic cancer.

 

----------------------------------------------------

[111]

TÍTULO / TITLE:  - Preoperative Chemoradiotherapy, Surgery and Adjuvant Therapy for Resectable Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hepatogastroenterology. 2013 Jan 16;60(126). doi: 10.5754/hge12974.

            ●● Enlace al texto completo (gratuito o de pago) 5754/hge12974

AUTORES / AUTHORS:  - Eguchi H; Nagano H; Tanemura M; Takeda Y; Marubashi S; Kobayashi S; Kawamoto K; Wada H; Hama N; Akita H; Mori M; Doki Y

RESUMEN / SUMMARY:  - Background/Aims: In order to improve the poor prognosis of pancreatic cancer, a combination therapy consisting of preoperative chemoradiotherapy, surgery and postoperative chemotherapy may be an ideal strategy; nevertheless, the influence  of preoperative therapy to postoperative therapy is not investigated. Methodology: Thirty patients with resectable pancreatic ductal adenocarcinoma were enrolled. A 40Gy of radiation (2Gy/day x 20 fractions/4 weeks) was administered together with intravenous infusion of gemcitabine (800mg/m2, days 1, 8 and 15) before surgery. Surgery was performed 3-7 weeks after the final fraction of radiation, and postoperative chemotherapy consisting of 1000mg/m2 gemcitabine (days 1, 8 and 15 every 4 weeks for 6 cycles) was started within 8 weeks after surgery. Results: All 30 patients successfully completed preoperative therapy. Re-staging after such therapy showed radiologically unresectable disease in 4 patients and 1 patient rejected surgery. Among the 25 patients who underwent laparotomy, 21 underwent curative resection. After curative resection, 4 were inadequate in performance status, thus postoperative therapy could not be started. Ten patients completed postoperative adjuvant therapy. Conclusions: The  combination therapy for resectable pancreatic cancer seems a feasible and effective approach, though preoperative therapy may reduce the feasibility of postoperative therapy.

 

----------------------------------------------------

[112]

TÍTULO / TITLE:  - Artificial neural networks predict survival from pancreatic cancer after radical  surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Surg. 2013 Jan;205(1):1-7. doi: 10.1016/j.amjsurg.2012.05.032.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.amjsurg.2012.05.032

AUTORES / AUTHORS:  - Ansari D; Nilsson J; Andersson R; Regner S; Tingstedt B; Andersson B

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Clinical Sciences Lund, Lund University, Skane University  Hospital, Lund, Sweden.

RESUMEN / SUMMARY:  - BACKGROUND: Artificial neural networks (ANNs) are nonlinear pattern recognition techniques that can be used as a tool in medical decision making. The objective of this study was to develop an ANN model for predicting survival in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: A flexible nonlinear survival model based on ANNs was designed by using clinical and histopathological data from 84 patients who underwent resection for PDAC. RESULTS: Seven of 33 potential risk variables were selected to construct the ANN, including lymph node metastasis, differentiation, body mass index, age, resection margin status, peritumoral inflammation, and American Society of Anesthesiologists grade. Three  variables (ie, lymph node metastasis, leukocyte count, and tumor location) were significant according to Cox regression analysis. Harrell’s concordance index for the ANN model was .79, and for Cox regression it was .67. CONCLUSIONS: For the first time, ANNs have been used to successfully predict individual long-term survival for patients after radical surgery for PDAC.

 

----------------------------------------------------

[113]

TÍTULO / TITLE:  - Distal splenorenal and temporary mesocaval shunting at the time of pancreatectomy for cancer: Initial experience from the Medical College of Wisconsin.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surgery. 2013 Jan 7. pii: S0039-6060(12)00732-5. doi: 10.1016/j.surg.2012.11.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2012.11.019

AUTORES / AUTHORS:  - Christians KK; Riggle K; Keim R; Pappas S; Tsai S; Ritch P; Erickson B; Evans DB

INSTITUCIÓN / INSTITUTION:  - Division of Surgical Oncology, Department of Surgery, Pancreatic Cancer Program,  Medical College of Wisconsin, Milwaukee, WI. Electronic address: kchristi@mcw.edu.

RESUMEN / SUMMARY:  - BACKGROUND: Vascular resection/reconstruction at the time of pancreatectomy is performed when limited vascular involvement is the only barrier to complete resection. Splenic vein (SV) ligation facilitates resection/reconstruction of the superior mesenteric vein (SMV)-portal vein (PV) confluence and widely exposes the superior mesenteric artery and celiac origin. If the inferior mesenteric vein does not provide for retrograde decompression, SV ligation may result in sinistral portal hypertension; creation of a distal splenorenal shunt (DSRS) can  prevent this complication. Additional complexity occurs in the setting of cavernous transformation of the PV. A mesocaval shunt (MCS) can be utilized to temporarily divert portal flow allowing for a safe portal dissection. Herein we report our initial experience utilizing DSRS and MCS at the time of pancreatectomy for cancer. METHODS: We reviewed all patients who underwent pancreatic resection for cancer and had either a DSRS and/or MCS performed between January 1, 2009 and February 1, 2012. RESULTS: Of 11 patients identified, 10 had adenocarcinoma, 9 underwent standard or extended pancreaticoduodenectomy,  and 2 underwent total pancreatectomy. Median operative time was 9.5 hours, median blood loss was 1,000 mL and median duration of stay was 10 days. There were no mortalities. There was 1 Clavien grade III complication during the index admission and 3 others were readmitted. No patient required reoperation. CONCLUSION: We provide proof of concept that extended pancreatic resection in the setting of limited vascular involvement can be safely performed. This is the first report utilizing MCS and DSRS to facilitate resection of the SMV-PV confluence in the setting of cavernous transformation of the PV.

 

----------------------------------------------------

[114]

TÍTULO / TITLE:  - 50 years ago in the journal of pediatrics: the effect of N-acetylcysteine on the  viscosity of tracheobronchial secretions in cystic fibrosis of the pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr. 2013 Jan;162(1):85. doi: 10.1016/j.jpeds.2012.08.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jpeds.2012.08.006

AUTORES / AUTHORS:  - Bear CE

INSTITUCIÓN / INSTITUTION:  - Program in Molecular Structure and Function, The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

 

----------------------------------------------------

[115]

TÍTULO / TITLE:  - Intrapapillary mucinous tumor of the pancreas (with video).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastrointest Endosc. 2013 Jan 21. pii: S0016-5107(12)02874-X. doi: 10.1016/j.gie.2012.11.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gie.2012.11.005

AUTORES / AUTHORS:  - El Majzoub NW; Eloubeidi MA

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine and the Division of Gastroenterology and Hepatology, The American University of Beirut Medical Center, Beirut, Lebanon.

 

----------------------------------------------------

[116]

TÍTULO / TITLE:  - Pancreatic duct lavage cytology with the cell block method for discriminating benign and malignant branch-duct type intraductal papillary mucinous neoplasms.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastrointest Endosc. 2013 Jan 2. pii: S0016-5107(12)02879-9. doi: 10.1016/j.gie.2012.11.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gie.2012.11.008

AUTORES / AUTHORS:  - Sai JK; Nobukawa B; Matsumura Y; Watanabe S

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Juntendo University, Tokyo, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Differentiation between benign and malignant branch-duct type intraductal papillary mucinous neoplasms (IPMNs) remains challenging. OBJECTIVE:  To examine the usefulness of pancreatic duct lavage cytology with cell block method for discriminating benign and malignant branch-duct type IPMNs. PATIENTS AND METHODS: Between December 2007 and April 2011, patients with branch-duct type IPMNs having mural nodules on EUS were examined by pancreatic duct lavage cytology by using the cell block method. Cell block sections underwent hematoxylin and eosin staining and mucin immunostainings (MUCs 1, 2, 5AC, and 6). DESIGN: Single-center, prospective study. SETTING: Academic medical center. MAIN  OUTCOME MEASUREMENTS: The sensitivity and specificity of cytology were assessed.  The agreement between cytological and histological results for MUC was also examined. RESULTS: Cytology with this method was investigated in 44 patients. Cell block diagnosis was cancer positive (class V or IV) in 11 patients and negative (classes I, II, III, and noninformative) in 33. The sensitivity, specificity, and positive and negative predictive values of this method were 92%, 100%, 100%, and 97%, respectively. The cytological and histological results of MUCs 1, 2, 5AC, and 6 agreed in 88% (15/17), 94% (16/17), 88% (15/17), and 100% (17/17), respectively. LIMITATIONS: Single center and small number of patients. CONCLUSIONS: Pancreatic duct lavage cytology with the cell block method may be useful to differentiate between benign and malignant IPMNs preoperatively and as  well as to determine their mucin type.

 

----------------------------------------------------

[117]

TÍTULO / TITLE:  - An evaluation of the accuracy of CT when determining resectability of pancreatic  head adenocarcinoma after neoadjuvant treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Radiol. 2012 Dec 31. pii: S0720-048X(12)00604-3. doi: 10.1016/j.ejrad.2012.12.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2012.12.002

AUTORES / AUTHORS:  - Cassinotto C; Cortade J; Belleannee G; Lapuyade B; Terrebonne E; Vendrely V; Laurent C; Sa-Cunha A

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Hopital du Haut-Leveque, Universitary Hospital Center of Bordeaux, France. Electronic address: christophe.cassinotto@chu-bordeaux.fr.

RESUMEN / SUMMARY:  - BACKGROUND: To evaluate the accuracy of MDCT for determination of resectability R0 after neoadjuvant therapy in patients with pancreatic head adenocarcinoma locally advanced. METHODS: From January 2005 to December 2010, 80 patients with pancreatic head adenocarcinoma underwent multidetector CT before surgery. Of these, 38 patients received neoadjuvant therapy because tumor was considered locally advanced on baseline CT scan. We retrospectively correlated imaging interpretations with operative and histological data and compared results in patients without (control group) or with (neoadjuvant group) preoperative treatment. RESULTS: 41/42 patients in control group and 31/38 patients in neoadjuvant group finally had curative resection. While resection R0 is similar in both groups (83% and 81%), CT accuracy in determining resectability R0 was significantly decreased in neoadjuvant group (58% versus 83%; p=0.039). CT scan specificity was significantly lower after neoadjuvant therapy (52% versus 88% in  control group) due to an overestimation of vascular invasion: 12/31 patients with complete resection in neoadjuvant group were evaluated at high risk of incomplete resection on CT scan. Tumor size tends to be underestimated in control group (-2mm) and overestimated in neoadjuvant group (+10mm). T-staging accuracy was decreased in neoadjuvant group (39% versus 78% in control group; p=0.002). CONCLUSION: Neoadjuvant therapy significantly decreases the accuracy of CT scan in determining operability, T-staging, and resectability R0 of pancreatic head carcinoma. Overestimation of tumor size and vascular invasion significantly reduces CT scan specificity after preoperative treatment.

 

----------------------------------------------------

[118]

TÍTULO / TITLE:  - Lymphoepithelial cyst of the pancreas in female children—report of two cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Surg. 2012 Dec;47(12):e51-4. doi: 10.1016/j.jpedsurg.2012.10.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jpedsurg.2012.10.006

AUTORES / AUTHORS:  - Ibrahim M; Ibrahim GK; Mohammad MA; Malami S; Umar AB; Nurkenovich AN; Rassulbek AR

INSTITUCIÓN / INSTITUTION:  - Murtala Mohammad Specialist Hospital, Department of Surgery, Kano, Nigeria. zarenawa1@yahoo.com

RESUMEN / SUMMARY:  - Lymphoepithelial cyst (LEC) of the pancreas is almost always reported as a case report or in small series mostly in male adult patients with vague clinical manifestations and difficult pre-operative diagnosis. Between the years 2007 and  2012, two female children with LEC of the pancreas were operated on at the Children’s Surgical Unit of Murtala Mohammad Specialist Hospital, Kano in northern Nigeria. Satisfactory outcomes were achieved after distal pancreatectomy and splenectomy in one and a Whipple procedure in the other. This benign lesion of the pancreas should be considered in the differential diagnosis of cystic lesions of the pancreas in children.

 

----------------------------------------------------

[119]

TÍTULO / TITLE:  - Does Autoimmune Pancreatitis Increase the Risk of Pancreatic Carcinoma?: A Retrospective Analysis of Pancreatic Resections.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826bef91

AUTORES / AUTHORS:  - Gupta R; Khosroshahi A; Shinagare S; Fernandez C; Ferrone C; Lauwers GY; Stone JH; Deshpande V

INSTITUCIÓN / INSTITUTION:  - From the *Department of Pathology, daggerDivision of Rheumatology, Department of  Medicine, and double daggerDepartment of Surgery, Massachusetts General Hospital  and Harvard Medical School, Boston, MA.

RESUMEN / SUMMARY:  - OBJECTIVES: To estimate the risk of malignancy in autoimmune pancreatitis (AIP).  METHODS: We examined resected pancreata to compare the prevalence of pancreatic intraepithelial neoplasia (PanIN) in 28 cases of AIP and 30 cases of chronic pancreatitis not otherwise specified (CP-NOS). We also reviewed a cohort of 84 AIP cases. RESULTS: The mean age of the AIP cohort (57 years) was significantly higher than that of the cohort of CP-NOS (47 years) (P = 0.01). Twenty-three cases (82%) of AIP showed PanIN, and 7 cases (25%) showed grade 2 PanIN. Grade 3  PanIN was identified in one case of AIP. There was no statistically significant difference in the number of cases with high-grade PanIN lesions between the cases of type 1 as opposed to type 2 AIP. In comparison to CP-NOS, a comparable percentage of patients with AIP had PanIN (82% of AIP cases vs 63% of CP-NOS cases) (P = NS) and PanIN 2 (25% AIP vs 20% CP-NOS) (P = NS). Of the 84 AIP cases at our institution (mean follow-up, 49 months), 2 cases of pancreatic carcinoma were identified 6 and 10 years after the diagnoses of AIP. CONCLUSIONS: These findings raise concern that AIP is associated with an elevated risk of malignancy and should prompt additional studies.

 

----------------------------------------------------

[120]

TÍTULO / TITLE:  - Evaluation of ADC measurements among solid pancreatic masses by respiratory-triggered diffusion-weighted MR imaging with inversion-recovery fat-suppression technique at 3.0T.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Magn Reson Imaging. 2012 Nov 29. pii: S0730-725X(12)00360-8. doi: 10.1016/j.mri.2012.09.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.mri.2012.09.006

AUTORES / AUTHORS:  - Yao XZ; Yun H; Zeng MS; Wang H; Sun F; Rao SX; Ji Y

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Zhongshan Hospital of Fudan University and Department of Medical Image, Shanghai Medical College of Fudan university, Xuhui District, Shanghai, 200032, China. Electronic address: yao.xiuzhong@zs-hospital.sh.cn.

RESUMEN / SUMMARY:  - PURPOSE: The objective of this paper was to investigate the value of apparent diffusion coefficients (ADCs) for differential diagnosis among solid pancreatic masses using respiratory triggered diffusion-weighted MR imaging with inversion-recovery fat-suppression technique (RT-IR-DWI) at 3.0T. MATERIALS AND METHODS: 20 normal volunteers and 72 patients (Pancreatic ductal adenocarcinoma [PDCA, n=30], mass-forming pancreatitis [MFP, n=15], solid pseudopapillary neoplasm [SPN, n=12], and pancreatic neuroendocrine tumor[PNET, n=15]) underwent  RT-IR-DWI (b values: 0 and 600s/mm(2)) at 3.0T. Results were correlated with histopathologic data and follow-up imaging. ADC values among different types of pancreatic tissue were statistically analyzed and compared. RESULTS: Statistical  difference was noticed in ADC values among normal pancreas, MFP, PDCA, SPN and PNET by ANOVA (p<.001). Normal pancreas had the highest ADC value, then followed  by PNET, PDCA, MFP and SPN. There was noticeable statistical difference in ADC values among PDCA, MFP and normal pancreas by Least Significant Difference (LSD)  (p<.001). ADC of SPN was statistically lower than that of PNET (p=0.1800x10(-4)), PDCA (p=0.0300x10(-4)) and normal pancreas (p=0.0007x10(-4)). ADC of PNET was statistically lower than that of normal pancreas (p=0.0360) and higher than that  of MFP (p=9.3000x10(-4)). CONCLUSIONS: ADC measurements using RT-IR-DWI at 3.0T may aid to disclose the histopathological pattern of normal pancreas and solid pancreatic masses, which may be helpful in characterizing solid pancreatic lesions.

 

----------------------------------------------------

[121]

TÍTULO / TITLE:  - Tumor-stroma interaction in orthotopic primary pancreatic cancer xenografts during Hedgehog pathway inhibition.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Cancer. 2012 Dec 27. doi: 10.1002/ijc.28006.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28006

AUTORES / AUTHORS:  - Chang Q; Foltz WD; Chaudary N; Hill RP; Hedley DW

INSTITUCIÓN / INSTITUTION:  - Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada.

RESUMEN / SUMMARY:  - To test the effects of Hedgehog pathway inhibition on the stroma of orthotopically-grown primary pancreatic cancer xenografts, and investigate the potential to monitor these effects non-invasively using magnetic resonance imaging (MRI), mice bearing orthotopically-grown primary pancreatic cancer xenografts were treated with the Hedgehog neutralizing antibody 5E1. Pathway inhibition was determined by RT-PCR using primer sets for human and mouse Hedgehog pathway genes, and effects on stroma assessed by automated image analysis of tissue sections stained for collagen and alpha-smooth muscle actin (alphaSMA). MRI provided quantitative biomarkers of stromal density based on magnetization transfer (MT-MRI) and dynamic contrast enhancement (DCE-MRI). Modest growth inhibition was seen in both models tested using 5E1, but was greater in OCIP19, which showed high expression of mouse Hedgehog pathway genes and an extensive fibrous stroma. However, despite profound inhibition of both mouse and human Hedgehog pathway genes, in neither model did we observe depletion of the stroma. Alignment of MT-MRI ratio images to histological sections showed co-registration with areas of fibrosis, although this was confounded by the presence of tumor necrosis. Due to the lack of stromal depletion by 5E1 it was not possible to determine the utility of MT-MRI for monitoring this effect. Cancer- and stromal cell-derived Hedgehog signaling elements are expressed in orthotopic primary pancreatic cancer xenografts, and selective targeting is growth-inhibitory. In contrast to some recent reports, growth inhibition does not involve attenuation of the tumor stroma, pointing to additional effects of Hedgehog signaling in pancreatic cancer. © 2012 Wiley Periodicals, Inc.

 

----------------------------------------------------

[122]

TÍTULO / TITLE:  - Lenalidomide in combination with gemcitabine as first-line treatment for patients with metastatic carcinoma of the pancreas: A Sarah Cannon Research Institute phase II trial.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Biol Ther. 2013 Jan 28;14(4).

AUTORES / AUTHORS:  - Infante JR; Arkenau HT; Bendell JC; Rubin MS; Waterhouse D; Jones GT; Spigel DR; Lane CM; Hainsworth JD; Burris HA

INSTITUCIÓN / INSTITUTION:  - Sarah Cannon Research Institute; Nashville, TN USA; Tennessee Oncology, PLLC; Nashville, TN USA.

RESUMEN / SUMMARY:  - Objectives: To evaluate the 6-mo overall survival, safety and tolerability of lenalidomide in combination with standard gemcitabine as first-line treatment for patients with metastatic pancreatic cancer. Methods: Eligibility included: previously untreated metastatic adenocarcinoma of the pancreas with metastases incurable by surgery/radiation therapy; ECOG PS 0-2; adequate organ function; prophylactic anticoagulation for venous thromboembolic events (VTEs). Patients received lenalidomide 25 mg PO (days 1-21) and gemcitabine 1,000 mg/m ( 2) IV (days 1, 8 and 15) each 28-day cycle, with response evaluations every eight weeks. Results: Between 5/2009-4/2010, 72 patients (median age 64 years; 68% male; 42% ECOG PS 0) were enrolled in this multicenter, community-based study. Six-month OS was 37% (95% CI 26-48%). Median PFS and OS were 2.3 (95% CI 1.9-3.5) and 4.7 (95% CI 3.4-5.7) months, respectively. Eight partial responses (11%) were documented. Thirty-nine patients (54%) experienced thrombocytopenia (2 patients,  3% grade 4). Hematologic toxicities resulted in dose modifications for the majority of patients. Twenty patients (28%) developed VTEs during treatment. Conclusions: The observed 6-month OS (37%) of lenalidomide with gemcitabine does  not suggest improvement compared with historical results with gemcitabine alone.  Toxicities and dose modifications likely limited dose intensity. Further development of this regimen in pancreas cancer is not recommended.

 

----------------------------------------------------

[123]

TÍTULO / TITLE:  - Minimally invasive treatment of pancreatic necrosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Gastroenterol. 2012 Dec 14;18(46):6829-35. doi: 10.3748/wjg.v18.i46.6829.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v18.i46.6829

AUTORES / AUTHORS:  - Bello B; Matthews JB

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, School of Medicine, University of Chicago, Chicago, IL 60637, USA.

RESUMEN / SUMMARY:  - AIM: To systematically review these minimally invasive approaches to infected pancreatic necrosis. METHODS: We used the MEDLINE database to investigate studies between 1996 and 2010 with greater than 10 patients that examined these techniques. Using a combination of Boolean operators, reports were retrieved addressing percutaneous therapy (341 studies), endoscopic necrosectomy (574 studies), laparoscopic necrosectomy via a transperitoneal approach (148 studies), and retroperitoneal necrosectomy (194 studies). Only cohorts with at least 10 or  more patients were included. Non-English papers, letters, animal studies, duplicate series and reviews without original data were excluded, leaving a total of 27 studies for analysis. RESULTS: Twenty-seven studies with 947 patients total were examined (eight studies on percutaneous approach; ten studies on endoscopic  necrosectomy; two studies on laparoscopic necrosectomy via a transperitoneal approach; five studies on retroperitoneal necrosectomy; and two studies on a combined percutaneous-retroperitoneal approach). Success rate, complications, mortality, and number of procedures were outcomes that were included in the review. We found that most published reports were retrospective in nature, and thus, susceptible to selection and publication bias. Few reports examined these techniques in a comparative, prospective manner. CONCLUSION: Each minimally invasive approach though was found to be safe and feasible in multiple reports. With these new techniques, treatment of infected pancreatic necrosis remains a challenge. We advocate a multidisciplinary approach to this complex problem with  treatment individualized to each patient.

 

----------------------------------------------------

[124]

TÍTULO / TITLE:  - High level of FOXC1 expression is associated with poor prognosis in pancreatic ductal adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2012 Dec 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-012-0617-7

AUTORES / AUTHORS:  - Wang L; Gu F; Liu CY; Wang RJ; Li J; Xu JY

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, First People’s Hospital of Changshu City, Changshu Hospital Affiliated to Soochow University, Changshu, 215500, Jiangsu Province, China.

RESUMEN / SUMMARY:  - Accumulating evidence for overexpression of FOXC1 in various types of human cancer suggests that it plays a key role in tumor biology. However, little is known about the function of FOXC1 in pancreatic ductal adenocarcinoma (PDA). This study was to investigate the expression profile of FOXC1 in PDA and its clinical  significance. We detected the expression profile of FOXC1 mRNA and protein in PDA tissue and in corresponding normal tissue by quantitative reverse-transcriptase polymerase chain reaction and western blotting. Immunohistochemistry was also used in the detection of FOXC1 protein expression. The clinicopathological implications of these proteins were analyzed statistically. Survival analysis was performed to assess prognostic significance. FOXC1 mRNA was overexpressed in PDA  tissue when compared with corresponding normal tissue, so was FOXC1 protein. The  overexpression of FOXC1 was significantly associated with the degree of clinical  stage (p < 0.001), histological differentiation (p = 0.002), and lymph node metastases (p < 0.001). Survival analysis revealed that overexpression of FOXC1 is associated with a poorer prognosis. These observations suggest that FOXC1 plays a key role in PDA and therefore may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in PDA.

 

----------------------------------------------------

[125]

TÍTULO / TITLE:  - Expression of UbcH10 in pancreatic ductal adenocarcinoma and its correlation with prognosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2013 Jan 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0671-9

AUTORES / AUTHORS:  - Zhao ZK; Wu WG; Chen L; Dong P; Gu J; Mu JS; Yang JH; Liu YB

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University, No. 1665, Kongjiang Rd., Shanghai, 200092, China.

RESUMEN / SUMMARY:  - The aim of this current study was to investigate the clinicopathologic features and prognostic significance of UbcH10 in pancreatic ductal adenocarcinoma (PDA).  Real-time quantitative RT-PCR was employed to examine UbcH10 expression in 20 pairs of PDA and adjacent non-cancerous tissues. In addition, UbcH10 expression was analyzed by immunohistochemistry in 94 clinicopathologically characterized PDA cases. The correlation of UbcH10 expression with patients’ survival rate was  assessed by Kaplan-Meier and Cox regression. Our results showed that the expression levels of UbcH10 mRNA and protein in PDA tissues were both significantly higher than those in non-cancerous tissues. Simultaneously, high expression of UbcH10 was significantly correlated with the clinical stage (p < 0.001), degree of histological differentiation (p < 0.001), and lymph node metastasis (p = 0.001). Moreover, high expression of UbcH10 was significantly associated with poor overall survival in PDA patients. In conclusion, UbcH10 might play a positive role in tumor development and could serve as an independent predictor of poor prognosis for PDA.

 

----------------------------------------------------

[126]

TÍTULO / TITLE:  - Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2012 Nov 29. pii: S0360-3016(12)03645-0. doi: 10.1016/j.ijrobp.2012.09.035.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.09.035

AUTORES / AUTHORS:  - Kelly P; Das P; Pinnix CC; Beddar S; Briere T; Pham M; Krishnan S; Delclos ME; Crane CH

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

RESUMEN / SUMMARY:  - PURPOSE: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC. METHODS AND MATERIALS: Medical records and  treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods. RESULTS: Twenty patients had treatment-related duodenal toxicity events, such as  duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade >/=2 was associated with tumor location, low platelet count, an absolute volume (cm(3)) receiving a dose of at least 55 Gy (V(55 Gy) > 1 cm(3)), and a maximum point dose >60 Gy. Of these factors, only V(55 Gy) >/=1 cm(3) was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002). CONCLUSIONS: This study demonstrates that a duodenal V(55 Gy) >1 cm(3) is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a dosimetric constraint when treating patients with unresectable pancreatic cancer  with concurrent chemoradiation.

 

----------------------------------------------------

[127]

TÍTULO / TITLE:  - MicroRNA expression signatures in intraductal papillary mucinous neoplasm of the  pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surgery. 2013 Jan 7. pii: S0039-6060(12)00729-5. doi: 10.1016/j.surg.2012.11.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2012.11.016

AUTORES / AUTHORS:  - Lubezky N; Loewenstein S; Ben-Haim M; Brazowski E; Marmor S; Pasmanik-Chor M; Oron-Karni V; Rechavi G; Klausner JM; Lahat G

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and the Nicolas and Elizabeth Slezak Cathedra in Experimental Surgery, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: nir_lubezky@hotmail.com.

RESUMEN / SUMMARY:  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) represent a spectrum  of tumors that range from low-grade (LG) dysplastic tumors to invasive cancer. Identification of IPMN at high risk for malignant transformation is important for the prevention and early treatment of pancreatic cancer. The roles of microRNA expression in the development of IPMN have not been extensively evaluated. METHODS: Expression patterns of 846 human microRNAs (miRNAs) was analyzed using microRNA microarray in 55 tissues, including LG IPMN (n = 10), moderate-grade (MG) IPMN (n = 5), high-grade (HG) IPMN (n = 5), invasive cancer with IPMN (IPMC; n = 10), pancreatic ductal adenocarcinoma without IPMN (PDA; n = 5), LG IPMN extracted from specimens that contain IPMC (LG_Ca; n = 10), and normal pancreatic tissues (n = 10). RESULTS: Fourteen miRNAs were differentially expressed in all IPMN tissues compared with normal pancreatic tissue. Expression level of 3 miRNAs was proportional to dysplasia level. Hierarchical clustering demonstrated grouping of 2 IPMN subgroups: LG and MG IPMN verses HG IPMN and IPMC. Expression  of 15 miRNAs was significantly different between these groups. LG_Ca tissues clustered with the HG IPMC group, and 12 miRNAs were differentially expressed in  LG_Ca, HG lesions, and IPMC compared with LG lesions. The expression patterns of  selected miRNAs were validated using quantitative reverse-transcription real-time polymerase chain reaction. Hierarchical clustering demonstrated microRNA expression profile in IPMC was significantly different from PDA, suggesting that  different pathways are involved in these cancer types. CONCLUSION: This study demonstrates that miRNAs are involved in the development and progression of IPMN. We identified potential targets for diagnosis, prognostication, and treatment of  IPMN.

 

----------------------------------------------------

[128]

TÍTULO / TITLE:  - Hyaluronan, fluid pressure, and stromal resistance in pancreas cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 15;108(1):1-8. doi: 10.1038/bjc.2012.569. Epub 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2012.569

AUTORES / AUTHORS:  - Provenzano PP; Hingorani SR

INSTITUCIÓN / INSTITUTION:  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinomas (PDAs) are notoriously aggressive and resistant to treatment. They distinguish themselves further by their robust fibroinflammatory, or desmoplastic, stromal reaction and degree of hypovascularity. Recent findings have revealed multiple mechanisms of stromal complicity in disease pathogenesis and resistance. In this review, we focus on altered physicomechanics as one mechanism of what we term as ‘stromal resistance’ in PDA. Extremely high interstitial fluid pressures and a dense extracellular matrix combine to limit the delivery and distribution of therapeutic agents. We discuss the genesis and consequences of altered fluid dynamics in PDA and strategies to restore them.

 

----------------------------------------------------

[129]

TÍTULO / TITLE:  - Toward the goal of personalized therapy in pancreatic cancer by targeting the molecular phenotype.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Adv Exp Med Biol. 2013;779:91-143. doi: 10.1007/978-1-4614-6176-0_5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-4614-6176-0_5

AUTORES / AUTHORS:  - Yee NS

INSTITUCIÓN / INSTITUTION:  - Division of Hematology-Oncology, Department of Medicine, Penn State College of Medicine, Penn State Hershey Cancer Institute, Milton S. Hershey Medical Center,  Pennsylvania State University, Hershey, PA, USA, nyee@hmc.psu.edu.

RESUMEN / SUMMARY:  - The purpose of this article is to provide a critical review of the molecular alterations in pancreatic cancer that are clinically investigated as therapeutic  targets and their potential impact on clinical outcomes. Adenocarcinoma of exocrine pancreas is generally associated with poor prognosis and the conventional therapies are marginally effective. Advances in understanding the genetic regulation of normal and neoplastic development of pancreas have led to development and clinical evaluation of new therapeutic strategies that target the signaling pathways and molecular alterations in pancreatic cancer. Applications have begun to utilize the genetic targets as biomarkers for prediction of therapeutic responses and selection of treatment options. The goal of accomplishing personalized tumor-specific therapy with tolerable side effects for patients with pancreatic cancer is hopefully within reach in the foreseeable future.

 

----------------------------------------------------

[130]

TÍTULO / TITLE:  - Usefulness of circulating tumor cell detection in pancreatic adenocarcinoma diagnosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Gastroenterol. 2013 Jan;108(1):152-5. doi: 10.1038/ajg.2012.367.

            ●● Enlace al texto completo (gratuito o de pago) 1038/ajg.2012.367

AUTORES / AUTHORS:  - Iwanicki-Caron I; Basile P; Toure E; Antonietti M; Lecleire S; Di Fiore A; Oden-Gangloff A; Blanchard F; Lemoine F; Di Fiore F; Sabourin JC; Michel P

INSTITUCIÓN / INSTITUTION:  - Digestive oncology Unit, Department of Hepatogastroenterology, Rouen University Hospital, University of Rouen, Rouen, France.

 

----------------------------------------------------

[131]

TÍTULO / TITLE:  - Malignant insulinoma misdiagnosed and treated as epilepsy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Endocrinol (Paris). 2013 Jan 22. pii: S0003-4266(12)01208-5. doi: 10.1016/j.ando.2012.11.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ando.2012.11.002

AUTORES / AUTHORS:  - Louda F; Chadli A; Elaziz S; Elghomari H; Farouqi A

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology and Diabetology, University Hospital Ibn Rochd, Riad  2 No. 198, El Alia Mohammedia 002010, Casablanca, Morocco. Electronic address: fatimalouda@yahoo.fr.

RESUMEN / SUMMARY:  - Pancreatic neuroendocrine tumors (PNET) are extremely rare, and although insulinomas are the commonest, less than 10% of insulinomas are malignant. Most patients with insulinomas present neuroglycopenic symptoms. Because of the rarity of the condition, we report the case of a 56-year-old man with malignant insulinoma, which was misdiagnosed as epilepsy. Timely diagnosis of this disease  is of paramount importance to prevent neurologic sequelae of hypoglycemia. Insulinomas should be regarded from the beginning as potentially malignant, although the majority of malignant insulinomas progresses slowly.

 

----------------------------------------------------

[132]

TÍTULO / TITLE:  - Long-Term Outcome of Laparoscopic Surgery for Pancreatic Neuroendocrine Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Surg. 2012 Dec 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00268-012-1893-5

AUTORES / AUTHORS:  - Haugvik SP; Marangos IP; Rosok BI; Pomianowska E; Gladhaug IP; Mathisen O; Edwin B

INSTITUCIÓN / INSTITUTION:  - Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Sognsvannsveien 20, 0372, Oslo, Norway, svhaug@ous-hf.no.

RESUMEN / SUMMARY:  - BACKGROUND: As most pancreatic neuroendocrine tumors (PNET) are relatively small  and solitary, they may be considered well suited for removal by a minimally invasive approach. There are few large series that describe laparoscopic surgery  for PNET. The primary aim of this study was to describe the feasibility, outcome, and histopathology associated with laparoscopic pancreatic surgery (LS) of PNET in a large series. METHODS: All patients with PNET who underwent LS at a single hospital from March 1997 to April 2011 were included retrospectively in the study. RESULTS: A total of 72 patients with PNET underwent 75 laparoscopic procedures, out of which 65 were laparoscopic resections or enucleations. The median operative time of all patients who underwent resections or enucleations was 175 (60-520) min, the median blood loss was 300 (5-2,700) ml, and the median  length of hospital stay was 7 (2-27) days. The overall morbidity rate was 42 %, with a surgical morbidity rate of 21 % and postoperative pancreatic fistula (POPF) formation in 21 %. Laparoscopic enucleations were associated with a higher rate of POPF than were laparoscopic resections. Five-year disease-specific survival rate was 90 %. The T stage, R stage, and a Ki-67 cutoff value of 5 % significantly predicted 5-year survival. CONCLUSION: LS of PNET is feasible with  acceptable morbidity and a good overall disease-specific long-term prognosis.

 

----------------------------------------------------

[133]

TÍTULO / TITLE:  - Role of PET/CT in the clinical management of locally advanced pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumori. 2012 Sep-Oct;98(5):643-51. doi: 10.1700/1190.13207.

            ●● Enlace al texto completo (gratuito o de pago) 1700/1190.13207

AUTORES / AUTHORS:  - Picchio M; Giovannini E; Passoni P; Busnardo E; Landoni C; Giovacchini G; Bettinardi V; Crivellaro C; Gianolli L; Di Muzio N; Messa C

INSTITUCIÓN / INSTITUTION:  - Nuclear Medicine, San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy. picchio.maria@hsr.it

RESUMEN / SUMMARY:  - AIM: To evaluate the role of 18F-fluorodeoxyglucose (FDG) PET/CT in: a) the selection of patients with locally advanced pancreatic cancer for helical tomotherapy with concurrent chemotherapy (HTT-ChT); b) monitoring HTT-ChT treatment efficacy in comparison with contrast-enhanced CT (c.e.CT). METHODS: Forty-two consecutive patients with unresectable locally advanced pancreatic cancer referred for HTT-ChT were enrolled in the study. All patients were pretreated with induction ChT. Before the beginning of HTT-ChT treatment patients underwent diagnostic c.e.CT (CT0) and FDG PET/CT (PET/CT0) for staging. After staging, patients received HTT-ChT. Three months after the end of HTT-ChT a control c.e.CT (CT1) was done. FDG PET/CT (PET/CT1) was repeated only in patients with positive PET/CT0. PET/CT1 and CT1 were compared with baseline imaging results to assess treatment efficacy. RESULTS: In 31/42 cases (74%) PET/CT0 documented pathological uptake in pancreatic lesions, while in the remaining 11/42 cases it showed no uptake. In 7/42 (17%) patients, PET/CT0 also detected distant metastases, prompting a change in the therapeutic approach. Compared to PET/CT0, PET/CT1 (n = 18) documented 3 complete metabolic responses, 9 partial metabolic responses, 2 instances of stable metabolic disease, and 4 instances of  progressive metabolic disease. In the same group of 18 patients, CT1 showed 0 complete responses, 3 partial responses, 8 instances of stable disease, and 7 instances of progressive disease compared to CT0. Concordance between PET/CT and  CT response was seen in 33% of cases. In 50% of cases, PET/CT1 documented a response to therapy that was not evident on CT. CONCLUSIONS: PET/CT influenced the treatment strategy by detecting distant metastases not documented by CT, thus accurately selecting patients for HTT-ChT after induction ChT. In monitoring treatment efficacy, PET/CT can detect a metabolic response to treatment not identified by CT.

 

----------------------------------------------------

[134]

TÍTULO / TITLE:  - A phase I study of sorafenib, oxaliplatin and 2 days of high dose capecitabine in advanced pancreatic and biliary tract cancer: a Wisconsin oncology network study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Invest New Drugs. 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10637-012-9916-5

AUTORES / AUTHORS:  - Loconte NK; Holen KD; Schelman WR; Mulkerin DL; Deming DA; Hernan HR; Traynor AM; Goggins T; Groteluschen D; Oettel K; Robinson E; Lubner SJ

INSTITUCIÓN / INSTITUTION:  - University of Wisconsin Carbone Cancer Center and the University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, K6/548 CSC, Madison, WI, 53792, USA, Ns3@medicine.wisc.edu.

RESUMEN / SUMMARY:  - Chemotherapy has yielded minimal clinical benefit in pancreatic and biliary tract cancer. A high-dose, short course capecitabine schedule with oxaliplatin, has shown some efficacy with a lower incidence of palmar-plantar erythrodysesthesia.  Achieving high exposures of the targeted agent sorafenib may be possible with this shorter schedule of capecitabine by avoiding dermatologic toxicity. All patients had pancreatic or biliary tract cancer. Patients in both cohorts received oxaliplatin 85 mg/m2 followed by capecitabine 2,250 mg/m2 PO every 8 h x 6 doses starting on days 1 and 15 of a 28 day cycle, or 2DOC (2 Day Oxaliplatin/Capecitabine). Cohort 1 used sorafenib 200 mg BID, and cohort 2 used  sorafenib 400 mg BID. Sixteen patients were enrolled. Across all cycles the most  common grade 1 or 2 adverse events were fatigue (10 pts), diarrhea (10 pts), nausea (9 pts), vomiting (8 pts), sensory neuropathy (8 pts), thrombocytopenia (7 pts), neutropenia (5 pts), and hand-foot syndrome (5 pts). Grade 3 toxicites included neutropenia, mucositis, fatigue, vomiting and diarrhea. Cohort 1 represented the MTD. Two partial responses were seen, one each in pancreatic and  biliary tract cancers. The recommended phase II dose of sorafenib in combination  with 2DOC is 200 mg BID. There were infrequent grade 3 toxicities, most evident with sorafenib at 400 mg BID.

 

----------------------------------------------------

[135]

TÍTULO / TITLE:  - Hemoglobin-Based Oxygen Carrier Mitigates Transfusion-Mediated Pancreas Cancer Progression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2842-0

AUTORES / AUTHORS:  - Lo KK; Bey EA; Patra B; Benson DD; Boothman DA; Silliman CC; Barnett CC Jr

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Denver Health Medical Center, University of Colorado Denver, Denver, CO, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Perioperative blood transfusion in pancreatic cancer patients is linked to decreased survival; however, a causal mechanism has not been determined. Previously we have shown that the plasma fraction of stored packed red blood cells (pRBCs) promotes pancreas cancer progression and associated morbidity. We hypothesize these untoward effects will be mitigated by use of a hemoglobin-based oxygen carrier (HBOC). METHODS: Cytokines and growth factors were measured in the plasma fraction from stored pRBCs and in an HBOC via cytokine array followed by formal enzyme-linked immunosorbent assay (ELISA). In an immunocompetent murine model, pancreas cancer progression was determined in vivo by bioluminescence, tumor weight, and number of metastases. RESULTS: Elevated levels of epidermal growth factor (EGF), platelet-derived growth factor  BB (PDGF-BB), and regulated upon activation, normal T cell expressed and secreted (RANTES) were present in the plasma fraction of stored pRBCs, but were not found  in the HBOC. Intravenous delivery of plasma fraction to mice with pancreatic cancer resulted in increased bioluminescence activity compared with mice that received HBOC. Metastatic events and pancreatic primary tumor weights were significantly higher in animals receiving plasma fraction from stored pRBCs compared with animals receiving HBOC. CONCLUSIONS: Intravenous receipt of the acellular plasma fraction of stored pRBCs promotes pancreatic cancer progression  in an immunocompetent mouse model. These untoward events are mitigated by use of  an HBOC.

 

----------------------------------------------------

[136]

TÍTULO / TITLE:  - Primary malignant pancreatic neoplasms in children and adolescents: a 20 year experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Surg. 2012 Dec;47(12):2199-204. doi: 10.1016/j.jpedsurg.2012.09.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jpedsurg.2012.09.005

AUTORES / AUTHORS:  - Rojas Y; Warneke CL; Dhamne CA; Tsao K; Nuchtern JG; Lally KP; Vasudevan SA; Hayes-Jordan AA; Cass DL; Herzog CE; Hicks MJ; Kim ES; Austin MT

INSTITUCIÓN / INSTITUTION:  - Department of Pediatric Surgery, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Malignant pancreatic neoplasms in children and adolescents are rare.  The clinical presentation, pathologic characteristics, management, and outcomes at two institutions are discussed. METHODS: We retrospectively reviewed all pediatric patients (age <= 18 years) treated for malignant pancreatic neoplasms at two institutions between 1991 and 2011. RESULTS: Thirty-one patients were identified with median age of 14.7 years (4-18 years). The most common histology  was solid pseudopapillary tumor (SPT) (n=22, 71%) followed by neuroendocrine tumors (n=4, 13%), pancreatoblastoma (n=4, 13%), and one unclassified spindle cell neoplasm (3%). Most patients presented with abdominal pain (n=22, 71%). Complications included pancreatic leak, pseudocyst formation, pancreatitis, pancreatic insufficiency, and small bowel obstruction. The overall 1- and 5-year  survival was 96% (95% CI 74%-99%) and 78% (95% CI 43%-93%). Median follow-up among patients alive at the end of follow-up was 20 months (<1 month-16.2 years). Patients with SPT had better overall survival compared to patients with neuroendocrine tumors or pancreatoblastomas (Log-rank; p=0.0143). CONCLUSION: The majority of pediatric and adolescent patients present with SPTs which are usually resectable and associated with an excellent prognosis. Other histologic subtypes  more often present with distant metastases and portend a worse prognosis.

 

----------------------------------------------------

[137]

TÍTULO / TITLE:  - Usefulness of 18F-FDG PET/CT in an unusual case of solid-pseudopapillary pancreatic tumor in childhood with aggressive behavior.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Jan;38(1):e35-7. doi: 10.1097/RLU.0b013e31824c5e92.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31824c5e92

AUTORES / AUTHORS:  - Treglia G; Caporale N; Rufini V; Callea F; Locatelli F; Giordano A

INSTITUCIÓN / INSTITUTION:  - Institute of Nuclear Medicine, Department of Bioimaging and Radiological Sciences, Catholic University of the Sacred Heart, and Department of Oncohematology, Pediatric Hospital Bambino Gesu, Rome, Italy. giorgiomednuc@libero.it

RESUMEN / SUMMARY:  - We report an unusual case of a solid-pseudopapillary pancreatic tumor (SPPT) with aggressive behavior that occurred in a 16-year-old male patient. (1)(8)F fluorodeoxyglucose PET/CT showed increased radiopharmaceutical uptake in a solid  mass of the body of the pancreas, in several liver lesions, and in multiple peritoneal implants, corresponding to an SPPT with liver and peritoneal metastases, respectively. Based on PET/CT findings, the patient was referred to chemotherapy. In this unusual case of pediatric SPPT with aggressive behavior, (1)(8)F fluorodeoxyglucose PET/CT has been useful in staging the disease and in treatment planning.

 

----------------------------------------------------

[138]

TÍTULO / TITLE:  - Quartz crystal microbalance with dissipation (QCM-D) as tool to exploit antigen-antibody interactions in pancreatic ductal adenocarcinoma detection.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biosens Bioelectron. 2012 Oct 22;42C:646-652. doi: 10.1016/j.bios.2012.10.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bios.2012.10.012

AUTORES / AUTHORS:  - Bianco M; Aloisi A; Arima V; Capello M; Ferri-Borgogno S; Novelli F; Leporatti S; Rinaldi R

INSTITUCIÓN / INSTITUTION:  - NNL-Institute of Nanoscience (NANO), CNR, Via per Arnesano 16, Lecce I-73100, Italy.

RESUMEN / SUMMARY:  - Novel synthetic peptides represent smart molecules for antigen-antibody interactions in several bioanalytics applications, from purification to serum screening. Their immobilization onto a solid phase is considered a key point for  sensitivity increasing. In this view, we exploited Quartz Crystal Microbalance with simultaneous frequency and dissipation monitoring (QCM-D) with a double aim, specifically, as investigative tool for spacers monolayer assembling and its functional evaluation, as well as high sensitive method for specific immunosorbent assays. The method was applied to pancreatic ductal adenocarcinoma  (PDAC) detection by studying the interactions between synthetic phosphorylated and un-phosphorylated alpha-enolase peptides with sera of healthy and PDAC patients. The synthetic peptides were immobilized on the gold surface of the QCM-D sensor via a self-assembled alkanethiol monolayer. The presented experimental results can be applied to the development of surfaces less sensitive to non-specific interactions with the final target to suggest specific protocols  for detecting PDAC markers with un-labeled biosensors.

 

----------------------------------------------------

[139]

TÍTULO / TITLE:  - Molecular markers in pancreatic cancer diagnosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Chim Acta. 2013 Jan 8. pii: S0009-8981(13)00005-3. doi: 10.1016/j.cca.2012.12.025.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cca.2012.12.025

AUTORES / AUTHORS:  - Herreros-Villanueva M; Gironella M; Castells A; Bujanda L

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Universidad del Pais Vasco UPV/EHU, San Sebastian, España; Division of Oncology Research, Schulze Center for Novel Therapeutics, College of Medicine, Mayo Clinic, Rochester, MN, United States.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) represents a fatal neoplasia with a high  mortality rate. Effective early detection methods are needed since this is the best way to cure this disease. During the last several years, many investigations focused on determining relevant biomarkers that may be present during early stages of pancreatic tumor development. Although several biomarkers have been proposed for pancreatic cancer detection, the clinical applicability has been confusing. Currently, although CA19-9 is one test used, the sensitivity and specificity for the disease are less than optimal. Here, we review several new potential serum, plasma and stool markers that are currently under evaluation. Although these have not been sufficiently validated for routine clinical use, these markers could prove valuable with further investigations. We keep the hope  that a combination of some of these novel biomarkers can be a useful tool for early PDAC diagnosis before image techniques and/or patient’s symptoms reveal disease in an incurable state.

 

----------------------------------------------------

[140]

TÍTULO / TITLE:  - Antitumor Effect of Everolimus in Preclinical Models of High Grade Gastroenteropancreatic Neuroendocrine Carcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuroendocrinology. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000347063

AUTORES / AUTHORS:  - Bollard J; Couderc C; Blanc M; Poncet G; Lepinasse F; Hervieu V; Gouysse G; Ferraro-Peyret C; Benslama N; Walter T; Scoazec JY; Roche C

INSTITUCIÓN / INSTITUTION:  - Endocrine Differentiation and Tumorigenesis Laboratory, Centre de Recherche en Cancerologie de Lyon, INSERM U1052-CNRS UMR5286, Universite de Lyon, Faculte Laennec, Lyon, France.

RESUMEN / SUMMARY:  - Background/Aims: While the range of therapeutic options for well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP NETs) has recently increased with the emergence of targeted therapies, such as mTOR inhibitors, there is no recent progress in the treatment of poorly differentiated neuroendocrine carcinomas (PDNECs). Since PDNECs have been shown to strongly express mTOR pathway components, the aim of the present study was to assess the antitumor effect of the mTOR inhibitor everolimus in preclinical models of PDNECs. Methods: Thee expression of mTOR pathway components and their response to everolimus were  assessed in two neuroendocrine cell lines: STC-1 and GluTag. A xenograft model of intra-hepatic dissemination in the nude mouse, based on the intrasplenic injection of either STC-1 and GluTag tumor cells, was used. Animals were started  on everolimus treatment 3 days after injection. The effects of treatment on tumor growth, proliferative capacities, apoptosis and in situ expression of mTOR pathway components were assessed. Results: The expression of mTOR pathway components was comparable in STC-1 and GluTag cells and in human PDNECs and could be inhibited in vitro by everolimus. In vivo, the tumor volume of STC-1 and GluTag xenografts was significantly reduced in treated animals (6.05% +/- 1.84 as compared to 21.76 +/- 3.88% in controls). Everolimus treatment also induced a significant decrease in Ki67 index and in the phosphorylation levels of the two major effectors of mTOR, p70S6K and 4E-BP1. Conclusion: Our experimental data suggest that mTOR inhibition could be considered a therapeutic option for high grade GEP NETs.

 

----------------------------------------------------

[141]

TÍTULO / TITLE:  - Diagnosis and management of cystic pancreatic lesions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AJR Am J Roentgenol. 2013 Feb;200(2):343-54. doi: 10.2214/AJR.12.8862.

            ●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.8862

AUTORES / AUTHORS:  - Sahani DV; Kambadakone A; Macari M; Takahashi N; Chari S; Castillo CF

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Division of Abdominal Imaging and Intervention, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, White 270, Boston, MA 02114.

RESUMEN / SUMMARY:  - OBJECTIVE: The purpose of this review is to outline the management guidelines for the care of patients with cystic pancreatic lesions. CONCLUSION: The guidelines are as follows: Annual imaging surveillance is generally sufficient for benign serous cystadenomas smaller than 4 cm and for asymptomatic lesions. Asymptomatic  thin-walled unilocular cystic lesions smaller than 3 cm or side-branch intraductal papillary mucinous neoplasms should be followed up with CT or MRI at  6 and 12 months interval after detection. Cystic lesions with more complex features or with growth rates greater than 1 cm/year should be followed more closely or recommended for resection if the patient’s condition allows surgery. Symptomatic cystic lesions, neoplasms with high malignant potential, and lesions  larger than 3 cm should be referred for surgical evaluation. Endoscopic ultrasound with fine-needle aspiration (FNA) biopsy can be used preoperatively to assess the risk of malignancy.

 

----------------------------------------------------

[142]

TÍTULO / TITLE:  - Notch 1 tumor expression is lacking in highly proliferative pancreatic neuroendocrine tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocrine. 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12020-012-9850-5

AUTORES / AUTHORS:  - Krausch M; Kroepil F; Lehwald N; Lachenmayer A; Schott M; Anlauf M; Cupisti K; Knoefel WT; Raffel A

INSTITUCIÓN / INSTITUTION:  - Department of General, Visceral and Pediatric Surgery, Heinrich-Heine-University  Dusseldorf, Moorenstrasse 5, 40225, Dusseldorf, Germany.

RESUMEN / SUMMARY:  - To date, very little is known about the development of benign organic hyperinsulinism and its metastatic potential. Typical morphologic, biochemical, or genetic differentiations for benign or malign tumor course of insulinomas do not exist. As signaling pathways may affect pancreatic cancer development and the maintenance of the neoplastic phenotype, the purpose of this study was to examine the role of Notch1 expression in organic hyperinsulinism. We examined 32 well-differentiated pancreatic endocrine tumors (wd PET); 11 wd PET of unknown behavior (wd PET ub); and 15 wd pancreatic endocrine cancer (wd PEC) for Notch1 expression by immunohistochemistry. Demographic data, clinical data, and follow-up of all patients were analyzed. Islets of the Langerhans show the strongest Notch1 staining in nearly 90 %. Positive Notch1 staining was absent in  the acinar of the pancreas. In patients with a wd PET more than every second tumor (56.3 %/n = 18/32) demonstrated a negative Notch1 staining. The other 14 patients were positive for Notch1. Tumors of unknown behavior (wd PET ub) and malignant insulinomas had no signs of Notch expression in contrast to benign insulinomas. Considering the clinical and histomorphological tumor behavior, no correlation between Notch1 expression and clinical data was found. The missing Notch expression in the malignant tumor course might be used as a potential predictive marker, but further studies are needed to investigate the underlying molecular mechanism.

 

----------------------------------------------------

[143]

TÍTULO / TITLE:  - Pancreatic Neuroendocrine Tumor Associated With Humoral Hypercalcemia of Malignancy and Carcinoid Tumor: A Case Report and Review of the Literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318267c987

AUTORES / AUTHORS:  - Shah RH; Martinez D

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, UCLA Medical Center, Los Angeles, CA, renashah@mednet.ucla.edu Department of Endocrinology, UCLA Medical Center, Los Angeles, CA.

 

----------------------------------------------------

[144]

TÍTULO / TITLE:  - Intrapancreatic gastric duplication cyst-A rare cause of chronic abdominal pain in childhood.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Ultrasound. 2013 Jan 9. doi: 10.1002/jcu.22029.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jcu.22029

AUTORES / AUTHORS:  - Lee CL; Daud CZ; Ismail RB

INSTITUCIÓN / INSTITUTION:  - Sabah Women and Children Hospital, Kota Kinabalu, Sabah, Malaysia. chiewleng@gmail.com.

RESUMEN / SUMMARY:  - We report a rare case of a gastric duplication cyst in the tail of the pancreas in a child presenting with chronic abdominal pain which was cured by excision of  the cyst and adjacent pancreas. This case report highlights the role of sonography as an excellent imaging tool for depiction of the bowel wall and, hence, in aiding diagnosis even when clinical picture and findings of other modalities are nonspecific. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 2013.

 

----------------------------------------------------

[145]

TÍTULO / TITLE:  - Concomitant Occurrence of Pulmonary Invasive Aspergillosis and Pneumocystis Pneumonia During FOLFIRINOX Chemotherapy for Pancreatic Carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2013 Jan;42(1):178-80. doi: 10.1097/MPA.0b013e31825486f8.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31825486f8

AUTORES / AUTHORS:  - Peron J; Derbel O; Penet AS; Stella M; Meeus P; Orlandini F; Perol M; Fouchardiere Cde L

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology University of Lyon-Leon Berard Cancer Center Lyon, France Department of Surgery University of Lyon-Leon Berard Cancer Center Lyon, France Department of Radiology University of Lyon-Leon Berard Cancer Center Lyon, France Department of Medical Oncology University of Lyon-Leon Berard Cancer Center Lyon, France christelle.delafouchardiere@lyon.unicancer.fr.

 

----------------------------------------------------

[146]

TÍTULO / TITLE:  - How Good Is Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Diagnosing the Correct Etiology for a Solid Pancreatic Mass?: A Meta-Analysis and Systematic Review.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2013 Jan;42(1):20-26.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e3182546e79

AUTORES / AUTHORS:  - Puli SR; Bechtold ML; Buxbaum JL; Eloubeidi MA

INSTITUCIÓN / INSTITUTION:  - From the *Division of Gastroenterology and Hepatology, Massachusetts General Hospital and Brigham Women’s Hospital, Harvard School of Medicine, Boston, MA; daggerDivision of Gastroenterology and Hepatology, University of Missouri-Columbia, Columbia, MO; double daggerDivision of Gastroenterology and Hepatology, University Southern California, Keck School of Medicine, CA; and section signDepartment of Medicine, the Division of Gastroenterology and Hepatology, and the Pancreatico-biliary Center, University of Alabama at Birmingham, Birmingham, AL.

RESUMEN / SUMMARY:  - OBJECTIVES: The objective of this study was to evaluate the accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in diagnosing the correct etiology for a solid pancreatic mass. METHOD: Data extracted from EUS-FNA studies with a criterion standard (either confirmed by surgery or appropriate follow-up) were selected. Articles were searched in MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials & Database of Systematic Reviews. Pooling was conducted by both fixed- and random-effects models. RESULTS: Initial search identified 3610 reference articles, of these 360 relevant articles were selected  and reviewed. Data were extracted from 41 studies (N = 4766) which met the inclusion criteria. Pooled sensitivity of EUS-FNA in diagnosing the correct etiology for solid pancreatic mass was 86.8% (95% confidence interval [CI], 85.5-87.9). Endoscopic ultrasound-guided FNA had a pooled specificity of 95.8% (95% CI, 94.6-96.7). Positive likelihood ratio of EUS was 15.2 (95% CI, 8.5-27.3), and the negative likelihood ratio was 0.17 (95% CI, 0.13-0.21). CONCLUSIONS: Endoscopic ultrasound-guided FNA is an excellent diagnostic tool to  detect the correct etiology for solid pancreatic masses. When available, EUS-FNA  should be strongly considered as the first diagnostic tool for sampling these lesions to optimize patient management.

 

----------------------------------------------------

[147]

TÍTULO / TITLE:  - A and B blood group antigens in human pancreatic ductal adenocarcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncology. 2013;84(3):141-9. doi: 10.1159/000345028. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345028

AUTORES / AUTHORS:  - Handra-Luca A

INSTITUCIÓN / INSTITUTION:  - Departments of Pathology, and Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Md., USA.

RESUMEN / SUMMARY:  - Objectives: The aim of this study was to determine the clinicopathological significance of blood group expression patterns in patients with surgically resected pancreatic ductal adenocarcinomas. Methods: Pancreatic ductal adenocarcinomas from 459 patients were analyzed for immunohistochemical expression of A and B blood group antigens on tissue microarrays. Correlations were established by Fisher’s test, chi(2) test, and logistic regression models, and relationships to postsurgical overall survival were analyzed by Kaplan-Meier  method, log-rank test, and multivariate Cox models. Results: Tumors expressing blood group A antigen predicted fewer lymph node metastases (<3) and had longer postoperative survival by univariate and multivariate analysis. Loss of A antigen tumor expression in A blood group type patients correlated to vascular invasion.  Conclusion: In patients with resectable pancreatic ductal adenocarcinomas, blood  group A antigen expression predicted fewer lymph node metastases and was associated with improved outcome after pancreaticoduodenectomy.

 

----------------------------------------------------

[148]

TÍTULO / TITLE:  - Combination chemotherapy of serine protease inhibitor nafamostat mesilate with oxaliplatin targeting NF-kappaB activation for pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Jan 21. pii: S0304-3835(13)00048-7. doi: 10.1016/j.canlet.2013.01.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.019

AUTORES / AUTHORS:  - Gocho T; Uwagawa T; Furukawa K; Haruki K; Fujiwara Y; Iwase R; Misawa T; Ohashi T; Yanaga K

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: gocho@jikei.ac.jp.

RESUMEN / SUMMARY:  - In this study, we assessed if nafamostat mesilate may enhance anti-tumor effects  of oxaliplatin on Panc-1 cells and pancreatic cancer mouse model. In combination  treatment with nafamostat mesilate and oxaliplatin, NF-kappaB activation was inhibited by suppressing IkappaBalpha phosphorylation, and caspase-8-mediated apoptosis was more prominent than that treated with oxaliplatin alone, both in vitro and in vivo. Nafamostat mesilate reduced proliferation rate of Panc-1 cells as compared with oxaliplatin alone in vitro and enhanced oxaliplatin-induced tumor growth inhibition in vivo. Combination chemotherapy using nafamostat mesilate and oxaliplatin induces synergistic cytotoxicity in pancreatic cancer and could be a novel strategy for treatment.

 

----------------------------------------------------

[149]

TÍTULO / TITLE:  - GANT-61 inhibits pancreatic cancer stem cell growth in vitro and in NOD/SCID/IL2R gamma null mice xenograft.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Mar 1;330(1):22-32. doi: 10.1016/j.canlet.2012.11.018. Epub 2012 Nov 28.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2012.11.018

AUTORES / AUTHORS:  - Fu J; Rodova M; Roy SK; Sharma J; Singh KP; Srivastava RK; Shankar S

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Laboratory Medicine, The University of Kansas Cancer  Center, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.

RESUMEN / SUMMARY:  - Multiple lines of evidence suggest that the Sonic Hedgehog (Shh) signaling pathway is aberrantly reactivated in pancreatic cancer stem cells (CSCs). The objectives of this study were to examine the molecular mechanisms by which GANT-61 (Gli transcription factor inhibitor) regulates stem cell characteristics  and tumor growth. Effects of GANT-61 on CSC’s viability, spheroid formation, apoptosis, DNA-binding and transcriptional activities, and epithelial-mesenchymal transition (EMT) were measured. Humanized NOD/SCID/IL2R gamma(null) mice were used to examine the effects of GANT-61 on CSC’s tumor growth. GANT-61 inhibited cell viability, spheroid formation, and Gli-DNA binding and transcriptional activities, and induced apoptosis by activation of caspase-3 and cleavage of Poly-ADP ribose Polymerase (PARP). GANT-61 increased the expression of TRAIL-R1/DR4, TRAIL-R2/DR5 and Fas, and decreased expression of PDGFRalpha and Bcl-2. GANT-61 also suppressed EMT by up-regulating E-cadherin and inhibiting N-cadherin and transcription factors Snail, Slug and Zeb1. In addition, GANT-61 inhibited pluripotency maintaining factors Nanog, Oct4, Sox-2 and cMyc. Suppression of both Gli1 plus Gli2 by shRNA mimicked the changes in cell viability, spheroid formation, apoptosis and gene expression observed in GANT-61-treated pancreatic CSCs. Furthermore, GANT-61 inhibited CSC tumor growth  which was associated with up-regulation of DR4 and DR5 expression, and suppression of Gli1, Gli2, Bcl-2, CCND2 and Zeb1 expression in tumor tissues derived from NOD/SCID IL2Rgamma null mice. Our data highlight the importance of Shh pathway for self-renewal and metastasis of pancreatic CSCs, and also suggest  Gli as a therapeutic target for pancreatic cancer in eliminating CSCs.

 

----------------------------------------------------

[150]

TÍTULO / TITLE:  - A rare case of acute pancreatitis induced by a gastrointestinal stromal tumor arising from the gastric fundus.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endoscopy. 2012 Dec;44 Suppl 2:E426-7. doi: 10.1055/s-0032-1325863. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1325863

AUTORES / AUTHORS:  - Sun J; Shen X; Li Z; Zhu J

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Jinan Central Hospital, Shandong University, Jinan, China.

 

----------------------------------------------------

[151]

TÍTULO / TITLE:  - The natural history of a branch-duct intraductal papillary mucinous neoplasm of the pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surgery. 2012 Dec 20. pii: S0039-6060(12)00686-1. doi: 10.1016/j.surg.2012.11.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2012.11.003

AUTORES / AUTHORS:  - Crippa S; Partelli S; Tamburrino D; Falconi M

INSTITUCIÓN / INSTITUTION:  - Division of Surgery, Ospedale “Sacro Cuore-Don Calabria,” Negrar, (VR), Italy; Department of Surgery, University of Verona, Verona, Italy; Division of Pancreatic and Digestive Surgery, Universita Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy. Electronic address: ste.crippa@libero.it.

 

----------------------------------------------------

[152]

TÍTULO / TITLE:  - FDG PET/CT Findings of Solid Pseudopapillary Tumor of the Pancreas With CT and MRI Correlation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318270868a

AUTORES / AUTHORS:  - Dong A; Wang Y; Dong H; Zhang J; Cheng C; Zuo C

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Nuclear Medicine, daggerPathology, Changhai Hospital; and double daggerDepartment of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

RESUMEN / SUMMARY:  - PURPOSE: The aim of this study was to evaluate retrospectively F-FDG PET/CT findings of solid pseudopapillary tumor of the pancreas (SPTP). PATIENTS AND METHODS: FDG PET/CT findings were reviewed in 8 patients with SPTP confirmed by pathology. Early PET/CT scans were performed 1 hour after FDG injection in all 8  patients. After an interval of 1 hour, delayed PET/CT scans were performed in 6 patients. All patients underwent enhanced CT and 4 patients underwent MRI. RESULTS: A total of 8 tumors were detected in all 8 patients. CT and MRI findings included encapsulation (n = 2), solid and cystic components (n = 4), focal calcification (n = 7), and weak enhancement during the arterial phase on enhanced CT or MRI and increasing enhancement during the portal venous phase (n = 8). All  the tumors showed increased FDG uptake. The mean SUVmax of all tumors was 8.9, with a high variability of SUVmax among lesions ranging from 2.5 to 29.1. The tumors (n = 6) with high cellularity had stronger FDG uptake, whereas the tumors  (n = 2) with low cellularity had relatively low FDG uptake. The tumors (n = 6) with pancreatic parenchymal, vascular, or perineural invasions had intense FDG uptake, whereas the tumors (n = 2) without invasions had slight-to-moderate FDG uptake. Two tumors with relatively high proliferative index had very strong FDG uptake, whereas those (n = 6) with low proliferative index or negative Ki-67 staining result had relatively lower FDG uptake. On delayed FDG PET/CT images, The SUVmax of SPTP increased in 4 patients and slightly decreased in 2 patients.  CONCLUSIONS: CT or MRI demonstrated morphological features of SPTP and FDG PET/CT that reflected the histopathological composition of the tumors. FDG uptake of SPTP may be related to tumor cellularity, proliferative index, or histological malignancy. Familiarity with the morphological and functional imaging findings of SPTP may be helpful for correct diagnosis and appropriate treatment.

 

----------------------------------------------------

[153]

TÍTULO / TITLE:  - Splenic artery aneurysm masquerading as a pancreatic tumor - diagnosis by contrast-enhanced endoscopic ultrasound.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endoscopy. 2012 Dec;44 Suppl 2:E428-9. doi: 10.1055/s-0032-1325861. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1325861

AUTORES / AUTHORS:  - Ogura T; Masuda D; Kurisu Y; Ohama H; Imoto A; Takii M; Takeuchi T; Inoue T; Tokioka S; Umegaki E; Higuchi K

INSTITUCIÓN / INSTITUTION:  - 2nd Department of Internal Medicine, Osaka Medical College, Osaka, Japan.

 

----------------------------------------------------

[154]

TÍTULO / TITLE:  - Usefulness of MALDI-TOF/MS Identification of Low-MW Fragments in Sera for the Differential Diagnosis of Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318273096c

AUTORES / AUTHORS:  - Padoan A; Seraglia R; Basso D; Fogar P; Sperti C; Moz S; Greco E; Marchet A; de Manzoni G; Zambon CF; Navaglia F; Cristadoro L; Di Chiara A; Nitti D; Pedrazzoli S; Pavanello G; Plebani M

INSTITUCIÓN / INSTITUTION:  - From the *Department of Laboratory Medicine, University of Padova; daggerCNR-ISTM; Departments of double daggerSurgical Oncological and Gastroenterological Sciences (DiSCOG) and section signMedicine (DIMED), University of Padova, Padova; parallelFirst Division of General Surgery, University of Verona, Verona; paragraph signGeneral Surgery, Pieve di Coriano Hospital, Mantova; and #SIPRES, Gruppo Pavanello, Padova, Italy.

RESUMEN / SUMMARY:  - OBJECTIVES: To identify new biomarkers of pancreatic cancer (PaCa), we performed  MALDI-TOF/MS analysis of sera from 22 controls, 51 PaCa, 37 chronic pancreatitis, 24 type II diabetes mellitus (DM), 29 gastric cancer (GC), and 24 chronic gastritis (CG). METHODS: Sera were purified by Sep-Pak C18 before MALDI-TOF/MS Anchorchip analysis. RESULTS: Features present in at least 5% of all spectra were selected (n = 160, m/z range, 1200-5000). At univariate analysis, 2 features (m/z 2049 and 2305) correlated with PaCa, 3 (m/z 1449, 1605, and 2006) with DM. No feature characterized gastric cancer or chronic gastritis. Ten-fold cross-validation binary recursive partitioning trees were obtained for patients’  classification. The tree (CA 19-9, age, m/z 2006, 2599, 2753, and 4997), built considering only patients with diabetes, allowed a distinction between DM [area under the receiver operating characteristic curve (AUC), 0.997], chronic pancreatitis (AUC, 0.968), and PaCa (AUC, 0.980), with an overall correct classification rate of 89%. The tree including CA 19-9, 1550, and 2937 m/z features, achieved an AUC of 0.970 in distinguishing localized from advanced PaCa. MALDI-TOF-TOF analysis revealed the 1550 feature as a fragment of Apo-A1, which was determined as whole protein and demonstrated to be closely correlated with PaCa. CONCLUSIONS: The findings made demonstrate a role for serum peptides identified using MALDI-TOF/MS for addressing PaCa diagnosis.

 

----------------------------------------------------

[155]

TÍTULO / TITLE:  - Endoscopic Ultrasound Elastography for Differential Diagnosis of Pancreatic Masses: A Meta-Analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Dig Dis Sci. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10620-012-2428-5

AUTORES / AUTHORS:  - Hu DM; Gong TT; Zhu Q

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

RESUMEN / SUMMARY:  - BACKGROUND: Distinguishing malignant from benign pancreatic tumors is challenging with current imaging techniques. Endoscopic ultrasound (EUS) elastography has further improved the efficacy of EUS for characterizing pancreatic lesions. AIMS: To assess, by combining data from existing trials, the accuracy of EUS elastography in diagnosing malignant tumors for patients with pancreatic masses.  METHODS: All relevant studies published were identified by systematic searching of databases. A meta-analysis was performed using a random-effects model to combine study results. RESULTS: Seven studies involving 752 patients were included. The sensitivity of EUS elastography for differential diagnosis of solid pancreatic masses was 97 % (95 % CI, 0.95-0.98), and the specificity was 76 % (95 % CI, 0.69-0.82). The area under the curve under summary receiver operating characteristic (SROC) was 0.9529. The combined positive likelihood ratio was 3.71 (95 % CI, 2.72-5.07), and the negative likelihood ratio was 0.05 (95 % CI, 0.02-0.13). CONCLUSION: Our meta-analysis shows that EUS elastography is a useful tool for differential diagnosis of solid pancreatic neoplasms with very high sensitivity and relatively low specificity. The results indicate that EUS elastography not only provides information complementary to that from EUS but also potentially increases the yield of fine needle aspiration and reduces the number of unnecessary biopsies.

 

----------------------------------------------------

[156]

TÍTULO / TITLE:  - Appraisal of the surgical management for pancreatic serous cystic neoplasms.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Endosc. 2013 Jan 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00464-012-2783-5

AUTORES / AUTHORS:  - Malleo G; Bassi C; Salvia R

INSTITUCIÓN / INSTITUTION:  - Unit of General Surgery B-Pancreas Institute, “G.B. Rossi” Hospital, Department of Surgery, University of Verona Hospital Trust, P.le L.A. Scuro 10, 37134, Verona, Italy, giuseppe.malleo@ospedaleuniverona.it.

 

----------------------------------------------------

[157]

TÍTULO / TITLE:  - Is Peng’s pancreaticojejunal anastomosis more effective than mucosa-mucosa anastomosis in duodenopancreatectomy for pancreatic and peri-ampullary tumours?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cir Esp. 2012 Dec 5. pii: S0009-739X(12)00175-3. doi: 10.1016/j.ciresp.2012.04.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ciresp.2012.04.010

AUTORES / AUTHORS:  - Targarona J; Barreda L; Pando E; Barreda C

INSTITUCIÓN / INSTITUTION:  - Departamento de Cirugia General, Hospital Edgardo Rebagliati Martins, Lima, Peru. Electronic address: jtargaronam@gmail.com.

RESUMEN / SUMMARY:  - INTRODUCTION: The pancreatic fistula is the most feared complication after a duodenopancreatectomy, and is the most common independent factor of post-surgical mortality. Peng et al. recently published a pancreaticojejunal anastomosis technique (binding anastomosis) which showed 0% pancreatic fistulas. The objective of this study is to evaluate and validate this new anastomosis technique compared with the conventional pancreaticoduodenectomy with end-to-side duct-to-mucosa anastomosis. MATERIAL AND METHOD: A prospective, non-randomised study was conducted to evaluate and validate this new anastomosis technique compared with the conventional pancreaticojejunal terminolateral duct to mucosa anastomosis. The study included 63 patients who were subjected to a duodenopancreatectomy due to having a pancreatic or periampullary neoplasm. A binding pancreaticojejunostomy according to the technique described by Peng et al. was performed on 30 patients (Group A), and a pancreaticoduodenectomy with end-to-side duct-to-mucosa anastomosis (conventional technique) was performed on  33 patients (Group B). RESULTS: When the results of the 2 techniques were compared, 2/30 (6%) of patients had a pancreatic fistula with the Peng technique, and 4/33 (12%) with the conventional technique, but this was not statistically significant (P=.674). Nor were there any significant differences between the 2 groups on comparing, morbidity, hospital stay and mortality. CONCLUSION: The results of this study show that the anastomosis method described by Peng is safe, but is not associated with a lower frequency of pancreatic fistula, general morbidity, or mortality. This leads to the uncertainty of whether it really has any advantages over other techniques.

 

----------------------------------------------------

[158]

TÍTULO / TITLE:  - Delta like ligand 4 induces impaired chemo-drug delivery and enhanced chemoresistance in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Mar 1;330(1):11-21. doi: 10.1016/j.canlet.2012.11.015. Epub 2012 Nov 27.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2012.11.015

AUTORES / AUTHORS:  - Kang M; Jiang B; Xu B; Lu W; Guo Q; Xie Q; Zhang B; Dong X; Chen D; Wu Y

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Second Affiliated Hospital, Zhejiang University School of  Medicine, Hangzhou, China; Key Laboratory of Cancer Prevention and Intervention,  China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

RESUMEN / SUMMARY:  - The stubborn chemoresistance of pancreatic ductal adenocarcinoma (PDA) is simultaneously influenced by tumor parenchymal and stromal factors, and the ctritical role of Notch ligand Delta-like 4 (DLL4) in the regulation of tumor malignancies has been observed. DLL4 positive expression ratio between duct cells from clinical tumor and adjacent tissues was statistically significant, and the overactivation of DLL4/Notch pathway enhanced the phenotype of EMT and cancer stem cell, even can induce multi-chemoresistance in vitro. Notably, the accompanied defective angiogenesis directly induced inefficient chemo-drug delivery in vivo. Collectively, overexpressed DLL4 on neoplastic cells can enhance chemoresistance through angiogenesis-dependent/independent mechanisms in  PDA.

 

----------------------------------------------------

[159]

TÍTULO / TITLE:  - Ratio of Pancreatic Duct Caliber to Width of Pancreatic Gland by Endosonography Is Predictive of Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31827305b8

AUTORES / AUTHORS:  - Eloubeidi MA; Luz LP; Tamhane A; Khan M; Buxbaum JL

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Gastroenterology and Hepatology; and daggerBiostatistics, University of Alabama in Birmingham, Birmingham, AL.

RESUMEN / SUMMARY:  - OBJECTIVES: This study aimed to determine whether (1) a pancreatic duct (PD) diameter to pancreatic gland width (G) ratio (PDG) by endoscopic ultrasonography  (EUS) predicts pancreatic cancer (PC) and (2) whether this ratio better indicates PC compared to PD dilation alone. METHODS: Patients presenting for EUS were classified into the following 4 categories: (1) normal, (2) noncalcific chronic pancreatitis (NCCP), (3) calcific CP (CCP), and (4) PC. RESULTS: There were 198 patients enrolled. Final diagnoses were PC (n = 34), CCP (n = 16), and normal/NCCP (n = 148). The median PD diameter (8, 5, and 2 mm, respectively; P =  <0.001), G (16, 20, and 17 mm, respectively; P = 0.002), and PDG ratio were significantly different among groups (0.54, 0.25, and 0.12, respectively; P < 0.001). Patients with PC were more likely to have a PDG ratio of greater than or  equal to 0.34 compared to CCP, and normal/NCCP groups (94%, 19%, 1.3%, respectively; P < 0.001). The positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of PDG greater than or equal to 0.34 for detecting cancer were 87%, 99%, 94%, 97%, and 97%, respectively. The accuracy and positive predictive value of PD dilation alone for diagnosing PC were 83% and 50%, respectively. CONCLUSIONS: A PDG ratio is a good predictor of PC and is better than PD dilation. This sign should be routinely used by endosonographers to improve EUS diagnostic capability of PC.

 

----------------------------------------------------

[160]

TÍTULO / TITLE:  - Incidental Neuroendocrine Tumors of the Pancreas: MDCT Findings and Features of Malignancy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AJR Am J Roentgenol. 2013 Feb;200(2):355-62. doi: 10.2214/AJR.11.8037.

            ●● Enlace al texto completo (gratuito o de pago) 2214/AJR.11.8037

AUTORES / AUTHORS:  - Gallotti A; Johnston RP; Bonaffini PA; Ingkakul T; Deshpande V; Castillo CF; Sahani DV

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, University Hospital “G. B. Rossi,” University of Verona, Verona, Italy.

RESUMEN / SUMMARY:  - OBJECTIVE: The objective of our study was to evaluate the MDCT features of incidentally detected neuroendocrine tumors (NETs) of the pancreas, identify features that can predict tumor biology or aggressiveness and long-term outcome,  and determine the incidence of “nonbenign” behavior. MATERIALS AND METHODS: In this retrospective study, 60 histologically verified pancreatic NETs incidentally detected with contrast-enhanced MDCT were included. Various MDCT features such as size, morphology, enhancement, and presence of calcifications were evaluated and  were correlated with tumor biology on histopathology. The sensitivity, specificity, predictive values, and accuracy were calculated for MDCT features in predicting nonbenign biology and risk of recurrence. RESULTS: A total of 32 of 60 (53%) NETs were nonbenign: most were large (mean, 29.1 mm) with a solid or complex pattern. NET size of 3 cm or larger yielded a positive predictive value of 61% for nonbenign tumors and 100% when calcification was present. In 12 patients with recurrence, 92% of NETs were nonbenign. The presence of calcification, local invasion, main pancreatic duct dilatation, vascular invasion, and lymph node enlargement along with angioinvasion and a Ki-67 index greater than 2% on histology were associated with a nonbenign diagnosis and a higher risk of recurrence. CONCLUSION: Approximately 50% of incidental NETs show  uncertain or malignant behavior. Solid tumors 3 cm or larger are commonly nonbenign; however, about 30% of tumors smaller than that size cutoff can be malignant. Nonbenign tumors and those with invasive features on MDCT have a higher incidence of recurrence.

 

----------------------------------------------------

[161]

TÍTULO / TITLE:  - ABCB2 (TAP1) as the downstream target of SHH signaling enhances pancreatic ductal adenocarcinoma drug resistance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Jan 20. pii: S0304-3835(13)00021-9. doi: 10.1016/j.canlet.2013.01.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.002

AUTORES / AUTHORS:  - Xu M; Li L; Liu Z; Jiao Z; Xu P; Kong X; Huang H; Zhang Y

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

RESUMEN / SUMMARY:  - Hedgehog signaling plays critical roles in drug resistance of PDAC. We demonstrate that SHH is highly expressed in PDAC patients and cell lines. SHH signaling protects PDAC cells against gemcitabine induced apoptosis, because either over-expression or knockdown of SHH in PDAC cells affects the sensitivity  to gemcitabine. Mechanistic studies show that ABCB2 serves as the downstream target of SHH signaling, leading to the drug resistance of PDAC cells. Combinational treatments with gemcitabine and cyclopamine yield synergistic antitumor effects in vitro and in vivo. Our study suggests that inhibiting SHH signaling or targeting ABCB2 gene improves the efficacy of chemotherapy in patients with PDAC.

 

----------------------------------------------------

[162]

TÍTULO / TITLE:  - Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Mar;29(3):1124-32. doi: 10.3892/or.2012.2210. Epub 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2012.2210

AUTORES / AUTHORS:  - Hao K; Tian XD; Qin CF; Xie XH; Yang YM

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, Peking University First Hospital, Beijing 100034,  P.R. China.

RESUMEN / SUMMARY:  - Pancreatic cancer is one of the most aggressive and devastating malignancies. The Hedgehog (Hh) pathway has been reported to play an important role in pancreatic cancer development and progression. The aim of this study was to examine the activation of the Hh pathway in human pancreatic cancer tissue samples and pancreatic cancer cell lines, and the molecular mechanisms involved in the Hh pathway mediated effects on pancreatic cancer cell proliferation and invasion. The expression levels of Hh molecules in human pancreatic cancer tissue samples and pancreatic cancer cell lines were evaluated using RT-PCR. The role of the Hh  pathway in cell proliferation and invasion was evaluated using flow cytometry, MTT, colony formation assays and transwell invasion assays, and the expression of cancer stem cell markers and epithelial-mesenchymal transition (EMT) were evaluated using flow cytometry and RT-PCR. Tumorigenicity assays were used to further investigate the role of the Hh pathway in vivo. Hh molecules were highly  expressed in human pancreatic cancer tissue samples and pancreatic cancer cell lines. Inhibition of the Hh pathway notably decreased cell proliferation and induced apoptosis through inhibition of the PI3K/AKT pathway and cancer stem cells. Furthermore, inhibition of the Hh signaling pathway significantly inhibited EMT by suppressing the activation of transcription factors Snail and Slug, which are correlated with significantly reduced pancreatic cancer cell invasion, suggesting that the Hh signaling pathway is involved in early metastasis. These results indicate that activation of the Hh pathway is a common  event. Inhibition of the Hh pathway may be a potential molecular target of new therapeutic strategies for pancreatic cancer.

 

----------------------------------------------------

[163]

TÍTULO / TITLE:  - Role of (18) F-fluorodeoxyglucose positron emission tomography/computed tomography in the characterization of pancreatic masses: Experience from tropics.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastroenterol Hepatol. 2013 Feb;28(2):255-61. doi: 10.1111/jgh.12068.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jgh.12068

AUTORES / AUTHORS:  - Santhosh S; Mittal BR; Bhasin D; Srinivasan R; Rana S; Das A; Nada R; Bhattacharya A; Gupta R; Kapoor R

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine and PET, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

RESUMEN / SUMMARY:  - BACKGROUND AND AIM: Early detection and differentiation of malignant from benign  pancreatic tumors is very essential as mass-forming pancreatitis is a frequently  encountered problem. Positron emission tomography (PET) has a role in establishing the diagnosis of pancreatic carcinoma when the conventional imaging  modalities or biopsies are nondiagnostic. In this prospective study, the utility  of fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in the characterization  of mass-forming lesions of the pancreas was reported. METHODS: (18) F-FDG-PET/CT  was prospectively performed in 87 patients diagnosed to have periampullary or pancreatic mass. Lesions with focally increased FDG uptake in PET/CT were considered malignant, whereas those with diffuse or no FDG uptake were considered benign. Semiquantitative analysis with maximum standardized uptake value (SUVmax) was also calculated. The PET/CT results were compared with histopathological results in all patients. RESULTS: Based on the FDG uptake pattern, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for FDG-PET/CT in characterizing the periampullary and pancreatic masses into benign and malignant lesions were 93%, 90%, 95%, 87%, and 92% respectively. Receiver operating characteristics curve analysis of the SUVmax of the lesions yielded a cut-off value of 2.8, with a sensitivity and specificity of 87.5% and 45% respectively. CONCLUSION: The FDG uptake pattern in PET/CT can differentiate  malignant from benign mass-forming lesions of the pancreas with high accuracy and a discrete cut-off value of SUVmax could not be defined for the same as even lesions with pancreatic tuberculosis showed very high FDG uptake. Hence, in patients with a suspicion of malignancy in the pancreas, a focally increase FDG uptake in PET/CT suggests the diagnosis of malignancy.

 

----------------------------------------------------

[164]

TÍTULO / TITLE:  - Gastric Intramural Pseudocyst: A Rare Complication of Pancreatic Pseudocyst.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2013 Jan;42(1):182-184.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e3182546e56

AUTORES / AUTHORS:  - Oka A; Amano Y; Uchida Y; Kagawa K; Tada Y; Kusunoki R; Fukuba N; Moriyama I; Yuki T; Ishihara S; Kinoshita Y

INSTITUCIÓN / INSTITUTION:  - Second Department of Internal Medicine Shimane University School of Medicine Izumo, Shimane, Japan Division of Endoscopy Shimane University Hospital Izumo, Shimane, Japan amano@med.shimane-u.ac.jp Department of Gastroenterology Matsue Red Cross Hospital Matsue, Shimane, Japan Second Department of Internal Medicine  Shimane University School of Medicine Izumo, Shimane, Japan Division of Endoscopy Shimane University Hospital Izumo, Shimane, Japan Second Department of Internal Medicine Shimane University School of Medicine Izumo, Shimane, Japan.

 

----------------------------------------------------

[165]

TÍTULO / TITLE:  - Role of Endoscopic Ultrasonography in Evaluation of Metastatic Lesions to the Pancreas: A Tertiary Cancer Center Experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826c276d

AUTORES / AUTHORS:  - Atiq M; Bhutani MS; Ross WA; Raju GS; Gong Y; Tamm EP; Javle M; Wang X; Lee JH

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Gastroenterology, daggerPathology, double daggerRadiology, section signMedical Oncology, and parallelBiostatistics, University of Texas-MD Anderson Cancer Center, Houston, TX.

RESUMEN / SUMMARY:  - OBJECTIVES: Metastatic lesions to the pancreas pose diagnostic challenges with regards to their differentiation from primary pancreatic cancer. Data on the yield of endoscopic ultrasonography (EUS)-guided fine-needle aspiration in detection of these lesions are limited. METHODS: This is a retrospective review of 23 patients referred to a tertiary referral center for further evaluation of suspected pancreatic metastases. Main outcome measures were diagnostic yield of endoscopic ultrasonography-guided fine-needle aspiration in evaluation of metastatic lesions to the pancreas. RESULTS: Of 644 patients, 23 (3.6%) undergoing EUS of the pancreas were diagnosed to have metastatic disease to the pancreas based on clinical, radiological, and cytological results. Mean (SD) age  was 64.3 (11.7) years. Of the 23 patients, 18 (78.3%) were asymptomatic. Mean (SD) size of lesion on EUS was 39.1 (19.9) mm. A diagnosis of malignant lesion was made in 21 of 23 cases, with a diagnostic accuracy of 91.3%. CONCLUSIONS: Metastatic lesions to the pancreas present as incidental, solitary mass lesions on staging or surveillance imaging. Endoscopic ultrasonography-guided fine-needle aspiration is an important tool in the characterization and further differentiation of metastatic lesions to the pancreas from primary pancreatic cancer.

 

----------------------------------------------------

[166]

TÍTULO / TITLE:  - Lentivirus-mediated shRNA interference targeting vascular endothelial growth factor inhibits angiogenesis and progression of human pancreatic carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Mar;29(3):1019-26. doi: 10.3892/or.2012.2203. Epub 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2012.2203

AUTORES / AUTHORS:  - Zhao X; Zhu DM; Gan WJ; Li Z; Zhang JL; Zhao H; Zhou J; Li DC

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

RESUMEN / SUMMARY:  - Angiogenesis is known to be essential to the survival, growth, invasion and metastasis of cancer cells. Vascular endothelial growth factor (VEGF) is an important factor regulating tumor angiogenesis. In the present study, we analyzed the effect of lentivirus-mediated shRNA interference targeting vascular endothelial growth factor (VEGF) on angiogenesis and progression in the pancreatic cancer cell line Patu8988 in vitro and in vivo. The study aimed to construct a recombinant lentivirus carrying targeted VEGF shRNA (LV-RNAi) to be used to transfect Patu8988 cells, and we investigated its anti-angiogenic and growth inhibitory effects on pancreatic cancer. VEGF expression was measured by RQ-PCR, western blotting and enzyme-linked immunosorbent assay (ELISA). In subcutaneous transplantation models, tumor volumes were determined, and the expression levels of VEGF and CD34 were assessed by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was used to determine apoptosis. In the orthotopic transplantation models, tumor volume and liver metastasis were determined. We successfully constructed LV-RNAi  and confirmed that it knocked down the VEGF gene at the mRNA and protein levels in Patu8988 cells. In the subcutaneous transplantation models, tumors with low levels of VEGF expression exhibited reduced pancreatic carcinoma angiogenesis and growth, and the apoptotic index was significantly higher. In the orthotopic transplantation models, tumors with low levels of VEGF expression exhibited significantly reduced pancreatic carcinoma growth, but no significant difference  was observed between the three mouse groups, LV-RNAi, LV-NC and the control, in regards to liver metastasis. In summary, lentivirus-mediated RNAi silencing of VEGF inhibited tumor angiogenesis and growth, and increased apoptosis of the pancreatic cancer cell line Patu8988. VEGF targeted gene silencing approach has the potential to serve as a novel treatment for pancreatic cancer.

 

----------------------------------------------------

[167]

TÍTULO / TITLE:  - Cystic pancreatic neuroendocrine tumors: endoscopic ultrasound and fine-needle aspiration characteristics.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endoscopy. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1325990

AUTORES / AUTHORS:  - Yoon WJ; Daglilar ES; Pitman MB; Brugge WR

INSTITUCIÓN / INSTITUTION:  - Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

RESUMEN / SUMMARY:  - Background and study aims: Limited data are available on the endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) characteristics of cystic pancreatic neuroendocrine tumors (CPanNets). The aims of this study were to describe the EUS and FNA characteristics of pathologically confirmed CPanNets and to compare these characteristics with mucinous cysts from matched patients.Patients and methods: From an EUS - FNA database (between 1999 and 2011), 19 patients with a pathologically confirmed CPanNet were identified. Patient characteristics, cyst fluid carcinoembryonic antigen (CEA) levels, pathology, and EUS findings were analyzed. For comparison, age- and sex-matched patients with mucinous cysts were randomly chosen from the same database.Results: Of the 19 patients, two had multiple endocrine neoplasia type 1 and two had metastases. The median diameter of the lesions was 24 mm. EUS revealed unilocular lesions in 7 patients, thinly septated lesions with thin walls in 1, and mixed solid-cystic lesions in 11. EUS - FNA cytology confirmed neoplasm in 12 of the 19 patients (63.2 %). The median cyst fluid CEA level (n = 15) was 1.1 ng/mL (range  0.3 - 500 ng/mL). Compared with matched patients with mucinous cysts, the median  cyst fluid CEA was lower (1.1 ng/mL vs. 400 ng/mL), thick walls were more common  (66.7 % vs. 13.3 %), and diagnostic cytology was more likely (73.3 % vs. 20.0 %).Conclusions: Analysis of EUS and FNA results showed that the cyst fluid from CPanNets had a lower CEA concentration, a higher frequency of thick walls on EUS, and higher diagnostic cytology compared with mucinous cysts. These findings may aid in the diagnosis of CPanNets.

 

----------------------------------------------------

[168]

TÍTULO / TITLE:  - Prognostic Significance of PUMA in Pancreatic Ductal Adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Int Med Res. 2012;40(6):2066-72.

AUTORES / AUTHORS:  - Du QH; Zhang KJ; Jiao XL; Zhao J; Zhang M; Yan BM; Xu YB

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Shandong Provincial-owned Hospital, Jinan, Shandong, China.

RESUMEN / SUMMARY:  - OBJECTIVES: To investigate retro spectively whether alterations of p53 upregulated mediator of apoptosis (PUMA) protein levels and somatic mutations of  the PUMA gene are characteristic of pancreatic ductal adenocarcinoma (PDAC). METHODS: Immunohistochemical analyses of PUMA were performed in pancreatic tumour tissue samples, and paired normal pancreatic tissue samples, from patients with PDAC. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assay. RESULTS: A total of 70 patients with PDAC had samples available; 49 cases (70.0%) had high PUMA protein  levels. PUMA was not detected in paired normal tissue samples. Significantly higher levels of PUMA protein were detected in low-grade tumours (tumour -node-metastasis stages I and II), compared with higher grade (stage III) tumours. Of the PDAC cases, the mean apoptosis index value for PUMA-positive specimens was significantly higher than that for PUMA-negative specimens. Overall survival was significantly associated with PUMA immunoreactivity. CONCLUSIONS: High levels of PUMA in PDAC tumour cells suggest that PUMA expression may play a  role in pancreatic tumourigenesis.

 

----------------------------------------------------

[169]

TÍTULO / TITLE:  - Marginally Calcified Totally Necrotic Tumor of the Pancreas: A Subset of Solid Pseudopapillary Tumor With Near-Total Necrosis?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2013 Jan;42(1):184-186.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318254f4f7

AUTORES / AUTHORS:  - Kang CM; Hwang HK; Kim H; Kim H; Chung YE; Park JS; Yoon DS; Lee WJ

INSTITUCIÓN / INSTITUTION:  - Department of Surgery College of Medicine Pancreatobiliary Cancer Clinic Institute of Gastroenterology Yonsei University Health System Seoul, Korea Department of Pathology College of Medicine Yonsei University Seoul, Korea Department of Radiology College of Medicine Yonsei University Seoul, Korea Department of Surgery College of Medicine Yonsei University Gangnam Severance Hospital Seoul, Korea dsy6110@yuhs.ac Department of Surgery College of Medicine Pancreatobiliary Cancer Clinic Institute of Gastroenterology Yonsei University Health System Seoul, Korea.

 

----------------------------------------------------

[170]

TÍTULO / TITLE:  - Genome-wide sequencing to identify the cause of hereditary cancer syndromes: With examples from familial pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2012 Nov 27. pii: S0304-3835(12)00655-6. doi: 10.1016/j.canlet.2012.11.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2012.11.008

AUTORES / AUTHORS:  - Roberts NJ; Klein AP

INSTITUCIÓN / INSTITUTION:  - Ludwig Center for Cancer Genetics and Therapeutics, The Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.

RESUMEN / SUMMARY:  - Advances in our understanding of the human genome and next-generation technologies have facilitated the use of genome-wide sequencing to decipher the genetic basis of Mendelian disease and hereditary cancer syndromes. However, the  application of genome-wide sequencing in hereditary cancer syndromes has had mixed success, in part, due to complex nature of the underlying genetic architecture. In this review we discuss the use of genome-wide sequencing in both Mendelian diseases and hereditary cancer syndromes, highlighting the potential and challenges of this approach using familial pancreatic cancer as an example.

 

----------------------------------------------------

[171]

TÍTULO / TITLE:  - Renal cell carcinoma metastases to the pancreas: value of arterial phase imaging  at MDCT.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Radiol. 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 1258/ar.2012.120693

AUTORES / AUTHORS:  - Corwin MT; Lamba R; Wilson M; McGahan JP

INSTITUCIÓN / INSTITUTION:  - University of California, Davis Medical Center, Department of Radiology, Sacramento, CA.

RESUMEN / SUMMARY:  - BackgroundThe pancreas is an increasingly recognized site of renal cell carcinoma metastases. It is important to determine the optimal MDCT protocol to best detect RCC metastases to the pancreas.PurposeTo compare the rate of detection of renal cell carcinoma metastases to the pancreas between arterial and portal venous phase MDCT.Material and MethodsA retrospective review of CTs of the abdomen yielded six patients with metastatic RCC to the pancreas. Five of six patients had pathologically proven clear cell RCC. Two blinded reviewers independently reported the number of pancreatic lesions seen in arterial and venous phases. Each lesion was graded as definite or possible. The number of lesions was determined by consensus review of both phases. Attenuation values were obtained for metastatic lesions and adjacent normal pancreas in both phases.ResultsThere were a total of 24 metastatic lesions to the pancreas. Reviewer 1 identified 20/24 (83.3%) lesions on the arterial phase images and 13/24 (54.2%) lesions on the venous phase. Seventeen of 20 (85.0%) arterial lesions were deemed definite and 9/13 (69.2%) venous lesions were definite. Reviewer 2 identified 19/24 (79.2%) lesions on the arterial phase and 14/24 (58.3%) on the venous phase. Seventeen of 19 (89.5%) arterial lesions were definite and 7/14 (50%) venous lesions were definite. Mean attenuation differential between lesion and pancreas  was 114 HU and 39 HU for arterial and venous phases, respectively (P < 0.0001).ConclusionDetection of RCC metastases to the pancreas at MDCT is improved using arterial phase imaging compared to portal venous phase imaging.

 

----------------------------------------------------

[172]

TÍTULO / TITLE:  - B7-H3 overexpression in pancreatic cancer promotes tumor progression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Mol Med. 2013 Feb;31(2):283-91. doi: 10.3892/ijmm.2012.1212. Epub 2012 Dec  13.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijmm.2012.1212

AUTORES / AUTHORS:  - Zhao X; Li DC; Zhu XG; Gan WJ; Li Z; Xiong F; Zhang ZX; Zhang GB; Zhang XG; Zhao H

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China.

RESUMEN / SUMMARY:  - B7-H3, a member of the B7-family molecules, plays an important role in adaptive immune responses. In addition, B7-H3 is also expressed in several types of human  cancers and is correlated with the poor outcome of cancer patients. However, its  exact role in cancer is not known. In the present study, we compared B7-H3 expression in normal pancreas and pancreatic cancer tissue specimens, and determined the effects of low B7-H3 expression on the human pancreatic cancer cell line Patu8988 using lentivirus-mediated RNA interference. B7-H3 expression in pancreatic specimens was determined by enzyme-linked immunosorbent assay (ELISA). A Patu8988 cell line with low B7-H3 expression was established by lentivirus-mediated RNA interference to investigate the effect of B7-H3 on cell proliferation, migration and invasion in vitro. By establishing subcutaneous transplantation tumor and orthotopic transplantation pancreatic cancer mouse models, the effect of B7-H3 on cell proliferation, migration and invasion was studied in vivo. B7-H3 in tissue samples was significantly higher in the pancreatic cancer group than in the normal pancreas group (mean +/- SD, 193.6+/-9.352 vs. 87.74+/-7.433 ng/g; P<0.0001). B7-H3 knockdown by RNA interference decreased cell migration and Transwell invasion up to 50% in vitro.  No apparent impact was observed on cell proliferation in vitro. In the subcutaneous transplantation tumor mouse model, the tumor growth rate was reduced by the knockdown of B7-H3. In the orthotopic transplantation pancreatic cancer mouse model, the effect of inhibiting metastasis by knocking down B7-H3 was assessed in terms of the average postmortem abdominal visceral metastatic tumor weight. This demonstrated that inhibition of B7-H3 expression reduced pancreatic  cancer metastasis in vivo. In conclusion, B7-H3 is aberrantly expressed in pancreatic cancer. In addition to modulating tumor immunity, B7-H3 may have a novel role in regulating pancreatic tumor progression.

 

----------------------------------------------------

[173]

TÍTULO / TITLE:  - Automatic differential diagnosis of pancreatic serous and mucinous cystadenomas based on morphological features.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Comput Biol Med. 2013 Jan 1;43(1):1-15. doi: 10.1016/j.compbiomed.2012.10.009. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.compbiomed.2012.10.009

AUTORES / AUTHORS:  - Song JW; Lee JH; Choi JH; Chun SJ

INSTITUCIÓN / INSTITUTION:  - Department of Computer & Information Engineering, Inha University, 253, Yonghyun-dong, Nam-gu, Incheon 402 751, Republic of Korea. Electronic address: sjw@datamining.inha.ac.kr.

RESUMEN / SUMMARY:  - Generally, pathological diagnosis using an electron microscope is time-consuming  and likely to result in a subjective judgment, because pathologists perform manual screening of tissue slides at high magnifications. Recently, the advent of digital pathology technology has provided the basis for convenient screening and  quantitative analysis by digitizing tissue slides through a computer system. However, a screening process with high magnification still takes quite a long time. To solve these problems, recently the use of computer-aided design techniques for performing pathologic diagnosis has been increasing in digital pathology. For pathological diagnosis, we need different diagnostic methods for different regions with different characteristics. Therefore, in order to effectively diagnose different lesions and types of diseases, a quantitative method for extracting specific features is required in computerized pathologic diagnosis. This study is about an automated differential diagnosis system to differentiate between benign serous cystadenoma and possibly-malignant mucinous cystadenoma. In order to diagnose cystic tumors, the first step is identifying a  cystic region and inspecting its epithelial cells. First, we identify the lumen boundary of a cyst using the Direction Cumulative Map considering 8-ways. Then, the Epithelial Nuclei Identification algorithm is used to discern epithelial nuclei. After that, three morphological features for the differential diagnosis of mucinous and serous cystadenomas are extracted. To demonstrate the superiority of the proposed features, the experiments compared performance of the classifiers learned by using the proposed morphological features and the classical morphological features based on nuclei. The classifiers in the simulations are as follows; Bayesian Classifier, k-Nearest Neighbors, Support Vector Machine, and Artificial Neural Network. The results show that all classifiers using the proposed features have the best classification performance.

 

----------------------------------------------------

[174]

TÍTULO / TITLE:  - Intraductal papillary mucinous neoplasm originating from a jejunal heterotopic pancreas: report of a case.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Today. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00595-012-0486-0

AUTORES / AUTHORS:  - Okamoto H; Fujishima F; Ishida K; Tsuchida K; Shimizu T; Goto H; Sato A; Satomi S; Sasano H

INSTITUCIÓN / INSTITUTION:  - Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan, hi_ok_0531@yahoo.co.jp.

RESUMEN / SUMMARY:  - We report a rare case of an intraductal papillary mucinous neoplasm (IPMN) originating from a jejunal heterotopic pancreas, found incidentally during surgery. A 75-year-old woman was referred to our department for surgical treatment of an abdominal aortic aneurysm (AAA) and a concurrent oropharyngeal tumor. During surgery to correct the AAA, we found a jejunal tumor incidentally and performed partial resection of the jejunum. Microscopically, the jejunal tumor showed dilated ducts containing intraluminal papillae lined with mucinous epithelium with low-grade cytological and architectural atypia within the pancreatic tissue. Immunohistochemical staining revealed MUC1 (-), MUC2 (-), MUC5AC (+), and MUC6 (-) proteins. To the best of our knowledge, only six cases of IPMN originating from a heterotopic pancreas have been reported in English, and this is the first report of an IPMN originating from a jejunal heterotopic pancreas.

 

----------------------------------------------------

[175]

TÍTULO / TITLE:  - Rapid on-site evaluation by endosonographer during endoscopic ultrasound-guided fine needle aspiration for pancreatic solid masses.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastroenterol Hepatol. 2013 Jan 10. doi: 10.1111/jgh.12122.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jgh.12122

AUTORES / AUTHORS:  - Hayashi T; Ishiwatari H; Yoshida M; Ono M; Sato T; Miyanishi K; Sato Y; Kobune M; Takimoto R; Mitsuhashi T; Asanuma H; Ogino J; Hasegawa T; Sonoda T; Kato J

INSTITUCIÓN / INSTITUTION:  - Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine.

RESUMEN / SUMMARY:  - BACKGROUND AND AIM: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an established diagnostic method for patients with suspected pancreatic ductal carcinoma (PDC). Rapid on-site evaluation (ROSE) has been reported to improve the accuracy. However, an on-site cytopathologist is not routinely available in many  institutions. One of the solutions may be ROSE by endosonographer. The aim was to examine whether diagnostic accuracy increases through ROSE by endosonographer using our cytological criteria. METHODS: Patients who underwent EUS-FNA of solid  pancreatic masses from January 2006 until August 2009 (n=53, Period 1) and September 2009 to April 2011 (n=85, Period 2) were retrospectively identified. Before initiating ROSE at the start of period 2, two endosonographers underwent training for cytological interpretation, which was focused on four cytological features of PDC: anisonucleosis, nuclear membrane irregularity, overlapping, and  enlargement. During EUS-FNA in period 2, endosonographers classified the Diff-Quik smears under three atypical grades and evaluated the adequacy. All diagnoses were made by one pathologist without knowledge of clinical information. RESULTS: The rate of “inconclusive” diagnoses, interpreted as “suspicious”, “atypical” and “inadequate for diagnosis” was reduced from 26.4% in period 1 to 8.2% in period 2 (P=0.004). Moreover, diagnostic accuracy was increased from 69.2% in period 1 to 91.8% in period 2 (P<0.001). CONCLUSIONS: This cytological grading system used in ROSE by endosonographers is invaluable for diagnosis of pancreatic solid masses.

 

----------------------------------------------------

[176]

TÍTULO / TITLE:  - Intraductal Polypoid Lipid-Rich Neuroendocrine Tumor of the Pancreas with Entrapped Ductules: Case Report and Review of the Literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocr Pathol. 2013 Jan 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12022-012-9231-x

AUTORES / AUTHORS:  - Hechtman JF; Franssen B; Labow DM; Gordon RE; Dimaio CJ; Wilck EJ; Carrasco-Avino G; Zhu H

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Mount Sinai School of Medicine, One Gustave L Levy Place, 1194, New York, NY, 10029, USA, jaclyn.hechtman@mountsinai.org.

RESUMEN / SUMMARY:  - Pancreatic neuroendocrine tumors of the main pancreatic duct are rare and usually small due to symptoms of pancreatic duct obstruction. We present a case of a large (3 cm), well-differentiated (G1) lipid-rich polypoid neuroendocrine tumor of the pancreas completely occluding the main pancreatic duct with non-neoplastic-entrapped ductules and CK19 positivity. Clinical, radiological, gross, microscopic, immunohistochemical, and ultrastructural findings are discussed. The literature pertaining to the unique features of this case is reviewed including clinical and pathologic pitfalls and the possible etiologic and prognostic significance of these findings.

 

----------------------------------------------------

[177]

TÍTULO / TITLE:  - Melatonin is involved in the apoptosis and necrosis of pancreatic cancer cell line SW-1990 via modulating of Bcl-2/Bax balance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biomed Pharmacother. 2012 Nov 15. pii: S0753-3322(12)00097-2. doi: 10.1016/j.biopha.2012.10.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biopha.2012.10.005

AUTORES / AUTHORS:  - Xu C; Wu A; Zhu H; Fang H; Xu L; Ye J; Shen J

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Canglang District, Suzhou 215006, Jiangsu Province, PR China.

RESUMEN / SUMMARY:  - Melatonin influences a number of physiological processes and is believed to play  an antitumoral role in several types of cancers, but its impact on pancreatic cancer is not fully clarified. The growth inhibitory effect of melatonin on pancreatic cancer cell line SW-1990 was detected in vitro and in vivo. Annexin V/PI assay was applied to detect apoptosis and necrosis in SW-1990 cells. Changes of Bcl-2 and Bax expression were investigated by RT-PCR and Western blot. An obvious growth inhibition was found in SW-1990 after melatonin or combined treatment with melatonin and gemicitabine through both apoptosis and necrosis in  vitro, and also found in transplanted tumors in nude mice. RT-PCR and Western blot showed that Bcl-2 expression was downregulated, while Bax expression was upregulated, after melatonin treatment. Melatonin may be a pro-apoptotic and pro-necrotic agent for pancreatic cancer cells via its modulation of Bcl-2/Bax balance.

 

----------------------------------------------------

[178]

TÍTULO / TITLE:  - Adjuvant Radiotherapy and Lymph Node Status for Pancreatic Cancer: Results of a Study From the Surveillance, Epidemiology, and End Results (SEER) Registry Data.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Oncol. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31826e0570

AUTORES / AUTHORS:  - Opfermann KJ; Wahlquist AE; Garrett-Mayer E; Shridhar R; Cannick L; Marshall DT

INSTITUCIÓN / INSTITUTION:  - Departments of *Radiation Oncology daggerMedicine, Division of Biostatistics and  Epidemiology, Medical University of South Carolina, Charleston, SC double daggerDepartment of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.

RESUMEN / SUMMARY:  - OBJECTIVES:: This study explores the relationship of lymph node ratio (LNR) and radiotherapy (RT) to overall survival (OS) for patients with resected pancreatic  cancer. The impact of adjuvant RT, number of lymph nodes (LN) resected, positive  LN resected, and disease extension was also evaluated. METHODS:: The SEER database from 1998 to 2006 was reviewed, and 3314 patients with nonmetastatic carcinoma of the pancreas, surgical resection, examination of the regional LN, and a survival of >2 months were identified. Of these, 1597 patients received RT. Cox proportional hazards regression models and the logrank test were used to determine whether specific variables were related to OS. RESULTS:: Median OS for  patients having surgery alone was 14 months (1-y survival 58.1%, 2-y survival 33.6%) and for patients having adjuvant RT was 19 months (1-y survival 73.5%, 2-y survival 41.4%), P<0.001. For patients with LNR of 0%, OS was better compared with patients with any LN involvement, regardless of treatment group. Multivariable analysis found OS significantly related to LNR, total LN resected,  positive resected LN, year of diagnosis, and regional extent of disease in patients without adjuvant RT. In patients who received adjuvant RT, OS significance was only persistent for LNR, the total LN resected, and positive resected LN. CONCLUSIONS:: A higher LNR was indicative of worse OS in all patients. A strong association with improvement in OS was seen in patients having received adjuvant RT.

 

----------------------------------------------------

[179]

TÍTULO / TITLE:  - Primary mixed germ cell tumor arising in the pancreatic head.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Surg. 2013 Jan;48(1):e21-4. doi: 10.1016/j.jpedsurg.2012.10.054.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jpedsurg.2012.10.054

AUTORES / AUTHORS:  - Wang J; Zheng Z; Qiu Y; Tou J; Liu W; Xiong Q; Gu W; Gao Z

INSTITUCIÓN / INSTITUTION:  - Children’s Hospital, Zhejiang University School of Medicine.

RESUMEN / SUMMARY:  - Germ cell tumors, comprised of gonadal and extra-gonadal types, are relatively rare tumors arising from primordial germ cells. Extra-gonadal germ cell tumors have been reported to occur at many non-gonadal locations, from the brain to the  sacrococcygeal region. However, primary germ cell tumors in the pancreas are extremely rare. Herein, we present the first case of a 12-month-old girl with a primary mixed germ cell tumor, consisting of both endodermal sinus tumor and mature teratoma, in the pancreatic head.

 

----------------------------------------------------

[180]

TÍTULO / TITLE:  - Ectopic pancreas presenting with pancreatitis and a mesenteric mass.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Surg. 2013 Jan;48(1):e29-32. doi: 10.1016/j.jpedsurg.2012.10.062.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jpedsurg.2012.10.062

AUTORES / AUTHORS:  - Ginsburg M; Ahmed O; Rana KA; Boumendjel R; Dachman AH; Zaritzky M

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, University of Chicago Medical Center, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. Electronic address: michael.ginsburg@uchospitals.edu.

RESUMEN / SUMMARY:  - Ectopic pancreas is defined by the presence of abnormally situated pancreatic tissue that lacks contact with normal pancreas and possesses its own duct system  and vascular supply. Ectopic pancreas in the gastrointestinal tract is not uncommon. Moreover, there are several reported cases of adult ectopic pancreatitis in the literature, but to date, only two cases of pediatric ectopic  pancreatitis have been reported. We describe a 15-year-old female with acute right upper quadrant pain and elevated serum lipase and amylase, in whom the radiological diagnosis was mesenteric soft tissue mass with adjacent inflammatory changes. The surgical pathology diagnosis, however, was mesenteric ectopic pancreas complicated by pancreatitis. We advocate for ectopic pancreatitis to be  considered in a pediatric patient with acute abdominal pain, laboratory findings  consistent with pancreatitis, and imaging findings of a mesenteric mass and normal orthotopic pancreas.

 

----------------------------------------------------

[181]

TÍTULO / TITLE:  - Hepatobiliary and Pancreatic: Fatal tumor embolism caused by hepatocellular carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastroenterol Hepatol. 2013 Feb;28(2):380. doi: 10.1111/jgh.12048.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jgh.12048

AUTORES / AUTHORS:  - Wu CH; Wong YC; Wu MY; Nan YY; Lin WL

INSTITUCIÓN / INSTITUTION:  - Division of Emergency and Critical Care Radiology, Chang Gung Memorial Hospital,  Chang Gung University, Gueishan, Taoyuan, Taiwan.

 

----------------------------------------------------

[182]

TÍTULO / TITLE:  - Pancreatic cancer - cost for overtreatment with gemcitabine.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Oncol. 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2012.744140

AUTORES / AUTHORS:  - Ansari D; Tingstedt B; Andersson R

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Clinical Sciences Lund , Skane University Hospital and Lund University , Sweden.

RESUMEN / SUMMARY:  - Gemcitabine has been the standard chemotherapeutic agent in pancreatic cancer. However, two-thirds of pancreatic tumors display low expression of human equilibrative nucleoside transporter 1 (hENT1), which mediates cellular entry of  the drug, and do not respond to gemcitabine therapy. The objective was to determine the costs of gemcitabine overtreatment and the cost-effectiveness of hENT1 testing using a Swedish pancreatic cancer cohort. Material and methods. The study population included 87 patients that were diagnosed with pancreatic cancer  during 2008-2010 at Skane University Hospital, Lund. A detailed review of treatments, side effects and resource utilization was performed. The proportion of hENT1-low was estimated at two-thirds based on previous evaluations of tumor samples from the Radiation Therapy Oncology Group (RTOG) trial 9704, the German AIO Pancreatic Cancer Group (AIO-PK) trial 0104, the Low hENT1 and Adenocarcinoma of the Pancreas (LEAP) trial and the authors’ own institution. The cost of the hENT1 test was estimated at euro50-200. Results. Sixty patients received gemcitabine and the other 27 best supportive care. Drug administration and hospitalization were the main expenditures. Grade 3 and 4 toxicities occurred in  42%, the most common being neutropenia (18%). The hospital costs related to gemcitabine overtreatment amounted to euro5358 per pancreatic cancer patient, corresponding to as much as one-third of the total treatment cost. The health economical costs amounted to euro9449 per patient when including indirect costs.  Using hENT1 testing to select patients for gemcitabine therapy would save euro8.6 million in Sweden each year. Conclusion. Total costs related to gemcitabine overtreatment were high. Individualizing gemcitabine treatment is cost-saving and would reduce unnecessary treatment-related toxicity.

 

----------------------------------------------------

[183]

TÍTULO / TITLE:  - Management of primary hepatopancreatobiliary small cell carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Surg Oncol. 2012 Dec 27. doi: 10.1002/jso.23305.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jso.23305

AUTORES / AUTHORS:  - Groeschl RT; Christians KK; Turaga KK; Gamblin TC

INSTITUCIÓN / INSTITUTION:  - Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVES: Primary small cell carcinomas (SCC) of the pancreas, liver, gallbladder, and bile ducts have only been described in case reports. We hypothesized that surgical treatment was associated with improved overall survival (OS) for patients with localized hepatopancreatobiliary SCC. METHODS: The Surveillance, Epidemiology, and End-Results (SEER) database was queried for patients with SCC from 1998 to 2008. Survival was analyzed with Cox proportional  hazards models. RESULTS: Eighty-five patients had nonmetastatic hepatopancreatobiliary SCC and operative treatment data. Hepatic SCC was associated with a 2 month median OS, and no patient underwent surgery. Stage-adjusted median OS for pancreatobiliary SCC patients undergoing resection (19 months, 95% confidence interval [CI]: 10-42 months) was greater than those who were not resected (8 months, 95% CI: 4-12 months, P = 0.0052). Both surgical  resection (hazard ratio [HR]: 0.42, 95% CI: 0.29-0.63, P < 0.001) and administration of radiation therapy (HR: 0.50, 95% CI: 0.35-0.71, P < 0.001) independently predicted prolonged OS in adjusted models. CONCLUSION: Surgical resection was associated with prolonged survival for patients with localized pancreatic, gallbladder, and biliary primaries. While we recognize several biases inherent in a population-based study, these results provide insight into the survival that can be achieved with surgical resection of SCC in these specific locations. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.

 

----------------------------------------------------

[184]

TÍTULO / TITLE:  - Extensive distal pancreatectomy for pancreatic tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2013 Jan;33(1):267-70.

AUTORES / AUTHORS:  - Nakamura M; Ohtsuka T; Nakashima H; Nagayoshi Y; Kono H; Tsutsumi K; Takahata S; Tanaka M

INSTITUCIÓN / INSTITUTION:  - Department of Digestive Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan. mnakamura@med.kawasaki-m.ac.jp.

RESUMEN / SUMMARY:  - Aim: The purpose of this study was to evaluate the feasibility and advantages of  extensive distal pancreatectomy (ExDP). PATIENTS AND METHODS: We retrospectively  analyzed our experience in 24 patients, who underwent ExDP or total pancreatectomy (TP) for the treatment of pancreatic cancer (22 patients) or benign tumor (two patients). RESULTS: ExDP was associated with less blood loss (p=0.0189), shorter operative times (p=0.024), lower rates of worsening of diabetes mellitus (p<0.0001), and shorter hospital stays (p=0.0009) than TP. ExDP also had a lower complication rate than TP (1/11 cases versus 4/13 cases), but this was not a significant difference. There was no difference in the curative resection rate for pancreatic cancer between the two procedures (p=0.685). CONCLUSION: ExDP is a feasible and function-preserving operation for the treatment of pancreatic tumors in the body of the pancreas near the portal vein.

 

----------------------------------------------------

[185]

TÍTULO / TITLE:  - Silencing of the ARP2/3 Complex Disturbs Pancreatic Cancer Cell Migration.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2013 Jan;33(1):45-52.

AUTORES / AUTHORS:  - Rauhala HE; Teppo S; Niemela S; Kallioniemi A

INSTITUCIÓN / INSTITUTION:  - Institute of Biomedical Technology, FIN_33014 University of Tampere, Finland. anne.kallioniemi@uta.fi.

RESUMEN / SUMMARY:  - BACKGROUND: Actin-related protein 2/3 (ARP2/3) complex is an actin nucleator responsible for actin cytoskeleton branching which is essential for efficient cell migration. MATERIALS AND METHODS: The expression of the seven ARP2/3 complex subunits was assessed in pancreatic cancer cell lines and in normal pancreatic samples by quantitative RT-PCR. siRNA-mediated silencing was used to study the contribution of each ARP2/3 complex member to pancreatic cancer cell migration. RESULTS: ARPC3 and ARPC4 were the most highly expressed complex members, while ARPC1B and ARPC2 were expressed at low levels. Silencing of the ARP2/3 complex subunits typically resulted in reduced cell migration capacity. In particular, silencing of ARPC4 significantly reduced cell migration in all studied cell lines, with a major impact on Hs700T and HPAFII migration (50% and 68% decrease,  p<0.001). CONCLUSION: We offer comprehensive expression data on the ARP2/3 complex members for pancreatic cancer and normal pancreas. In addition, we show cell line-specific differences in ARP2/3 complex subunit dependency on cell migratory potential, and suggest ARPC4 to be one of the key members of the ARP2/3 complex in pancreatic cancer.

 

----------------------------------------------------

[186]

TÍTULO / TITLE:  - PET/CT in the management and prognosis of pancreatic exocrine tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Jan;38(1):33-4. doi: 10.1097/RLU.0b013e318270892d.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318270892d

AUTORES / AUTHORS:  - Nanni C; Fanti S; Colletti PM; Rubello D

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Azienda Ospedaliero Universitaria di Bologna, Policlinico Sant’Orsola-Malpighi, Bologna, Italy.

 

----------------------------------------------------

[187]

TÍTULO / TITLE:  - NPTX2 Hypermethylation in Pure Pancreatic Juice Predicts Pancreatic Neoplasms.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Med Sci. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MAJ.0b013e31827b94b6

AUTORES / AUTHORS:  - Yao F; Sun M; Dong M; Jing F; Chen B; Xu H; Wang S

INSTITUCIÓN / INSTITUTION:  - Departments of Breast Surgery (FY, FJ, BC, HMX, SBW), Surgical Oncology (FY, FJ,  BC, HMX, SBW), Endoscopy (MJS); and General Surgery (MD), Research Unit of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

RESUMEN / SUMMARY:  - ABSTRACT:: The neuronal pentraxin II (NPTX2) gene is methylated in over 90% primary pancreatic cancer tissues but rarely in normal pancreatic ductal epithelia. Here, the authors investigated the utility of methylated NPTX2 as a diagnostic marker for pancreatic cancer in pure pancreatic juice samples of patients with benign and malignant pancreatic diseases, including pancreatic cancer, intraductal papillary mucinous neoplasm or chronic pancreatitis using methylation-specific polymerase chain reaction (MSP) and quantitative MSP. MSP assays revealed that the incidence of aberrant NPTX methylation in pure pancreatic juice samples was 64.5% (20 of 31) in patients with pancreatic cancer, 70.0% (7 of 10) in patients with malignant intraductal papillary mucinous neoplasm, 33.3% (2 of 6) in patients with benign intraductal papillary mucinous neoplasm and 21.7% (5 of 23) in patients with chronic pancreatitis. NPTX2 hypermethylation in patients with chronic pancreatitis was significantly lower than that of pancreatic cancer (P < 0.01) or patients with intraductal papillary  mucinous neoplasm (P < 0.05). At a cutoff value of 1.39 for quantitative MSP, the incidence of aberrant NPTX2 methylation was 61.3% (19 of 31) in patients with pancreatic cancer, 50.0% (5 of 10) in patients with malignant intraductal papillary mucinous neoplasm, 0% in patients with benign intraductal papillary mucinous neoplasm and 8.7% (2 of 23) in patients with chronic pancreatitis. There was a significant difference in NPTX2 methylation between pancreatic cancer and chronic pancreatitis (P < 0.01). Our findings indicate that detection of aberrant methylation of NPTX2 in pure pancreatic juice samples could be useful as a molecular marker to discriminate between patients with malignant and benign disease of the pancreas.

 

----------------------------------------------------

[188]

TÍTULO / TITLE:  - Hepatobiliary and Pancreatic: Clear cell myomelanotic tumor of ligamentum teres.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastroenterol Hepatol. 2013 Feb;28(2):381. doi: 10.1111/jgh.12047.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jgh.12047

AUTORES / AUTHORS:  - Coker D; Kench J; Ansari N; Zhou R; Sandroussi C

INSTITUCIÓN / INSTITUTION:  - University of Sydney Medical School, Sydney, Australia.

 

----------------------------------------------------

[189]

TÍTULO / TITLE:  - Gastrointestinal: Villous adenoma of the ampulla of Vater causing acute pancreatitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastroenterol Hepatol. 2013 Feb;28(2):379. doi: 10.1111/jgh.12050.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jgh.12050

AUTORES / AUTHORS:  - Costa A; Fasih N; Thipphavong S

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, The Ottawa Hospital, Ottawa, Canada.

 

----------------------------------------------------

[190]

TÍTULO / TITLE:  - Hepatobiliary and Pancreatic: Intrapancreatic splenunculus mimics a hypervascular neoplasm.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastroenterol Hepatol. 2013 Jan;28(1):205. doi: 10.1111/jgh.12014.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jgh.12014

AUTORES / AUTHORS:  - Chanyaputhipong J; Sittampalam K; Goh B; Cheow P

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, Singapore General Hospital, Singapore.

 

----------------------------------------------------

[191]

TÍTULO / TITLE:  - Pancreatic cancer: Lack of association between apparent diffusion coefficient values and adverse pathological features.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Radiol. 2013 Jan 10. pii: S0009-9260(12)00575-2. doi: 10.1016/j.crad.2012.11.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.crad.2012.11.006

AUTORES / AUTHORS:  - Rosenkrantz AB; Matza BW; Sabach A; Hajdu CH; Hindman N

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, NYU Langone Medical Center, 550 First Avenue, New York,  NY 10016, USA. Electronic address: Andrew.Rosenkrantz@nyumc.org.

RESUMEN / SUMMARY:  - AIM: To identify retrospectively potential associations between apparent diffusion coefficient (ADC) values of pancreatic adenocarcinoma and tumour grade  as well as other pathological features, using histopathological assessment from the Whipple procedure as the reference standard. MATERIALS AND METHODS: Thirty patients with pancreatic adenocarcinoma underwent magnetic resonance imaging (MRI) including diffusion-weighted imaging with b-values of 0 and 500 s/mm(2) before the Whipple procedure. Two radiologists independently recorded the ADC values of the tumour and benign pancreas for all cases. ADC values were compared  with histopathological findings following the Whipple procedure. RESULTS: The intra-class correlation coefficient was 0.689 for benign pancreas and 0.695 for tumours, indicating good inter-reader agreement for ADC values. The mean ADC value was significantly lower in tumours than in benign pancreas for both readers (reader 1: 1.74 +/- 0.34 x 10(-3) mm(2)/s versus 2.08 +/- 0.48 x 10(-3) mm(2)/s,  respectively, p = 0.006; reader 2: 1.69 +/- 0.41 x 10(-3) mm(2)/s versus 2.11 +/- 0.54 x 10(-3) mm(2)/s, respectively, p < 0.001). However, there was no significant difference in mean ADC between poorly and well/moderately differentiated tumours for either reader (reader 1: 1.69 +/- 0.36 x 10(-3) mm(2)/s versus 1.78 +/- 0.33 x 10(-3) mm(2)/s, respectively, p = 0.491; reader 2: 1.62 +/- 0.33 x 10(-3) mm(2)/s versus 1.75 +/- 0.49 x 10(-3) mm(2)/s, respectively, p = 0.405). The area under the curve (AUC) for differentiation of poorly and well/moderately differentiated tumours was 0.611 and 0.596 for readers 1 and 2, respectively, and was not significantly better than an AUC of 0.500 for  either reader (p >/= 0.306). In addition, ADC was not significantly different for either reader between tumours with stage T3 versus stage T1/T2, between tumours with and without metastatic peri-pancreatic lymph nodes, or between tumours located in the pancreatic head versus other pancreatic regions (p >/= 0.413). CONCLUSION: No associations between ADC values of pancreatic adenocarcinoma and tumour grade or other adverse pathological features were observed.

 

----------------------------------------------------

[192]

TÍTULO / TITLE:  - Large Pancreatic Mucinous Cystic Neoplasm during Pregnancy: What Should Be Done?.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gynecol Obstet Invest. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000346176

AUTORES / AUTHORS:  - Tica AA; Tica OS; Saftoiu A; Camen D; Tica VI

INSTITUCIÓN / INSTITUTION:  - Department of Mother and Child, Emergency County Hospital Craiova, Craiova, Romania.

RESUMEN / SUMMARY:  - Pancreatic mucinous cystic neoplasms are uncommon and their occurrence in pregnancy is extremely rare. The authors report the unique case of a newborn weighing 3,620 g, delivered vaginally with no complications by a patient with a large ‘silent’ pancreatic mucinous cystic neoplasms, and analyze the very few other reports. With no available protocol, this case highlights an interesting dilemma on the management of pregnancy and delivery as well on the timing of pancreatic surgery. Despite its limitations, MRI remains the most accurate investigation either for differentiating the mucinous from nonmucinous cysts or for evaluating the malignancy, but echography is also very useful. Without symptoms, all low-grade malignant potential tumors, independent of the moment of  their diagnosis during pregnancy, should be resected 2-3 months after delivery and we believe that the best option is a term vaginal birth, even in the presence of a large cyst and large fetus. On the contrary, all high-grade malignant potential tumors, discovered in the first two trimesters of pregnancy should be resected during the second trimester, and followed by a vaginal delivery at term. If high-grade malignant potential tumor is diagnosed in the third trimester, an early vaginal delivery followed by surgery is recommended. Finally, the patient’s preference is crucial.

 

----------------------------------------------------

[193]

TÍTULO / TITLE:  - The Role of EUS and EUS-FNA in the Management of Pancreatic Masses: Five-Year Experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hepatogastroenterology. 2013 Jan 24;60(126). doi: 10.5754/hge121100.

            ●● Enlace al texto completo (gratuito o de pago) 5754/hge121100

AUTORES / AUTHORS:  - Caglar E; Senturk H; Atasoy D; Sisman G; Canbakan BI; Tuncer M

RESUMEN / SUMMARY:  - Background/Aims: The efficacy of endoscopic ultrasound with fine-needle aspiration (EUS-FNA) in the diagnosis and staging of pancreatic malignancy is quite well established. The aim of this study is to describe a single-centre’s experience. Methodology: Data were collected retrospectively on all patients with solid pancreatic masses undergoing EUS-FNA from January 2006 to March 2011. In tumor cases, TNM staging using EUS was compared with the results of histopathological staging. Results: EUS-FNA of pancreatic lesions was performed in 125 patients. Of these patients, data of 75 were available (69% men, mean age  59.97+/-11.12 (SD) years); 58 (76%) of the lesions were ductal adenocarcinoma, 11 (14.5%) were chronic pancreatitis, 4 (%5) were intraductal papillary mucinous carcinoma (IPMN) and 2 (%3) were insulinoma. Diagnostic yield of the EUS-FNA procedure was 74.7% (56/75). Specimens from six patients were inadequate. In multivariate analysis, lesion diameter below 2cm was an independent predictor for the inadequacy of material (p=0.04). Conclusions: In patients with pancreatic mass with suspected malignancy, EUS-FNA provided a diagnosis with accuracy rate of 75%. Inadequate material with EUS-FNA was significantly more frequent in lesions below 2cm.

 

----------------------------------------------------

[194]

TÍTULO / TITLE:  - Multi-centric solid-pseudopapillary neoplasm of the pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):330. doi: 10.1007/s12032-012-0330-9. Epub 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0330-9

AUTORES / AUTHORS:  - Li HX; Zhang Y; Du ZG; Tang F; Qi XQ; Yin B; Jiang YJ; Yang F; Subedi S

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China.

RESUMEN / SUMMARY:  - Multi-centric solid-pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor: only 4 cases are reported in the literature. The clinical and pathological features have not yet been fully clarified. We report 3 cases of multi-centric SPN and discuss their clinical presentations and histological and immunohistochemical features, comparing with solitary SPN. Among the total of 7 cases, 6 were female and 1 was male. Patients had nonspecific symptoms at presentation. Tumors were often large and well demarcated with cystic degeneration and clear margin between lumps. Histologically, characteristic pseudopapilla was formed with uniform cells surrounding the delicate blood vessels. Tumor cells were positive for vimentin, synaptophysin, progesterone receptor, and CD10 and demonstrated nuclear localization of beta-catenin. The prognosis of patients was excellent after complete surgical resections. Multi-centric SPN shares similar clinical and pathological features to solitary SPN.

 

----------------------------------------------------

[195]

TÍTULO / TITLE:  - Undifferentiated carcinoma of the pancreas involving intraductal pedunculated polypoid growth.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Intern Med. 2012;51(24):3373-7. Epub 2012 Dec 15.

AUTORES / AUTHORS:  - Ishii S; Kobayashi G; Fujita N; Noda Y; Ito K; Horaguchi J; Koshita S; Kanno Y; Ogawa T; Masu K; Hashimoto S; Sawai T; Uzuki M

INSTITUCIÓN / INSTITUTION:  - Departemetnt of Gastroenterology, Sendai City Medical Center, Japan.

RESUMEN / SUMMARY:  - We herein report a case of pancreatic undifferentiated carcinoma involving intraductal pedunculated polypoid growth. Duodenoscopy disclosed a congested polypoid mass protruding from the orifice of the papilla of Vater. Endoscopic retrograde pancreatography (ERP) showed a polypoid lesion in Wirsung’s duct and Santorini’s duct. Pancreatic juice cytology using the cell block method revealed  the presence of undifferentiated carcinoma. No extraductal invasion was detected  on endoscopic ultrasonography and or intraductal ultrasonography. The patient therefore underwent pancreaticoduodenectomy. A histological examination revealed  an intraductal polypoid tumor with a thin stalk without extraductal invasion. The tumor was composed of an abundant mixture of pleomorphic cells, spindle cells, giant cells, and a small amount of adenocarcinoma.

 

----------------------------------------------------

[196]

TÍTULO / TITLE:  - Small serotonin-positive pancreatic endocrine tumors caused obstruction of the main pancreatic duct.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Gastroenterol. 2012 Dec 7;18(45):6669-73. doi: 10.3748/wjg.v18.i45.6669.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v18.i45.6669

AUTORES / AUTHORS:  - Ogawa M; Kawaguchi Y; Maruno A; Ito H; Nakagohri T; Hirabayashi K; Yamamuro H; Yamashita T; Mine T

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan. ma_ogawa@tokai-u.jp

RESUMEN / SUMMARY:  - We report 2 cases of pancreatic endocrine tumors that caused obstruction of the main pancreatic duct (MPD). A 49-year-old asymptomatic man was referred to our institution because dilation of the MPD was revealed by abdominal ultrasonography (US). No tumor was detected by endoscopic ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). The diameter of the MPD was > 20 mm at the body, and no dilation was noted at the head. Although malignancy was not confirmed through cytology or imaging, pancreatic cancer was strongly suspected.  Pancreaticoduo- denectomy was performed. Pathological and immunohistochemical examination revealed a 5 mm x 3 mm serotonin-positive endocrine tumor. Fibrosis was present around the MPD and seemed to cause stricture. A 32-year-old asymptomatic man had elevated serum amylase, and US demonstrated dilation of the  MPD. No tumor was detected by CT and MRI. Pancreatic cancer was suspected due to  stricture and dilation of the MPD. Pancreatectomy of middle part of pancreas was  performed. Pathological and immunohistochemical examination revealed a serotonin-positive endocrine tumor sized 5 mm x 4 mm. We report 2 cases of serotonin-positive pancreatic endocrine tumors that caused stricture of the MPD in spite of the small size of the tumor.

 

----------------------------------------------------

[197]

TÍTULO / TITLE:  - Sister Mary Joseph’s nodule as a first sign of pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Gastroenterol. 2012 Dec 7;18(45):6686-9. doi: 10.3748/wjg.v18.i45.6686.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v18.i45.6686

AUTORES / AUTHORS:  - Bai XL; Zhang Q; Masood W; Masood N; Tang Y; Cao CH; Fu QH; Zhang Y; Gao SL; Liang TB

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China.

RESUMEN / SUMMARY:  - Sister Mary Joseph’s nodule (SMJN) refers to a metastatic tumor of the umbilicus. It is a rare entity which arises from a malignancy in the intra-abdominal cavity. We herein describe a patient who presented with SMJN as his first sign of pancreatic cancer. It is an even more unusual case of SMJN. We therefore, suggest that pancreatic cancer should be included in the differential diagnosis when an umbilical mass is found. With the progress made in surgical procedures and other  modalities, an early diagnosis will dramatically improve the prognosis of the patients.

 

----------------------------------------------------

[198]

TÍTULO / TITLE:  - Neuroendocrine carcinoma of the pancreas with soft tissue metastasis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Gastroenterol. 2012 Dec 7;18(45):6682-5. doi: 10.3748/wjg.v18.i45.6682.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v18.i45.6682

AUTORES / AUTHORS:  - Chen J; Zheng Q; Yang Z; Huang XY; Yuan Z; Tang J

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Shanghai 6th People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.

RESUMEN / SUMMARY:  - Neuroendocrine carcinoma (NEC) of the pancreas is rare. We report the case of a 34-year-old man with pancreatic NEC with soft tissue metastasis. The patient presented with right upper abdominal discomfort. Computed tomography revealed a low-density heterogeneous mass in the tail and body of the pancreas that encroached on the greater curvature of the stomach and spleen. We performed exploratory laparotomy and total pancreatectomy with splenectomy and total gastrectomy. Histopathological analysis showed spindle-shaped cells with scanty cytoplasm and hyperchromatic nuclei, confirming a primary pancreatic NEC. One month after the surgery, the patient experienced leg swelling. Positron emission  tomography-computed tomography revealed high uptake of fludeoxyglucose in the left leg, and the leg was amputated. Histopathological analysis confirmed metastasis of pancreatic NEC. The patient was followed up and received chemotherapy (etoposide and cisplatin). One month after amputation, the level of  tumor marker neuron-specific enolase was 142.70 mug/L and computed tomography scan revealed an aggravated metastatic lesion. The patient suffered from unbearable pain and we treated him with odynolysis. Four months postoperatively,  the patient died of respiratory failure.

 

----------------------------------------------------

[199]

TÍTULO / TITLE:  - Spontaneous pancreatic pseudocyst-portal vein fistula: a rare and potentially life-threatening complication of pancreatitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann R Coll Surg Engl. 2013 Jan;95(1):7-9. doi: 10.1308/003588413X13511609955616.

            ●● Enlace al texto completo (gratuito o de pago) 1308/003588413X13511609955616

AUTORES / AUTHORS:  - Raza SS; Hakeem A; Sheridan M; Ahmad N

INSTITUCIÓN / INSTITUTION:  - Leeds Teaching Hospitals NHS Trust, UK.

RESUMEN / SUMMARY:  - Pseudocyst formation following acute and chronic pancreatitis is a well known complication. A pancreatic pseudocyst fistulating into the portal vein is a rare  and potentially fatal complication. We report a case of pancreatic pseudocyst - portal vein fistula, which was managed with a conservative approach.

 

----------------------------------------------------

[200]

TÍTULO / TITLE:  - Adenocarcinoma arising from heterotopic pancreas in the duodenum.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int Surg. 2012 Oct;97(4):351-5. doi: 10.9738/CC148.1.

            ●● Enlace al texto completo (gratuito o de pago) 9738/CC148.1

AUTORES / AUTHORS:  - Kinoshita H; Yamaguchi S; Shimizu A; Sakata Y; Arii K; Mori K; Nasu T

INSTITUCIÓN / INSTITUTION:  - 1 Department of Surgery and.

RESUMEN / SUMMARY:  - Abstract We present a rare case of adenocarcinoma arising from a heterotopic pancreas in the duodenum, and review the associated literature. A 62-year-old woman was admitted to our hospital, complaining of vomiting and epigastralgia. Imaging studies revealed advanced gastric cancer with a gastric outlet obstruction. Whipple’s operation and resection of the regional lymph node were performed because of a direct invasion to the pancreas. Histopathologic examination of the resected specimen demonstrated the malignant transformation of a hetrotopic pancreas in the duodenum. At the 12-month follow-up, there was no recurrence of symptoms. The prognosis of adenocarcinoma arising from a heterotopic pancreas is not known. Further accumulation of cases and investigation of this entity are necessary.

 

----------------------------------------------------

[201]

TÍTULO / TITLE:  - Inhibitory effects of acetylsalicylic acid on exocrine pancreatic carcinogenesis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biotech Histochem. 2013 Jan 21.

            ●● Enlace al texto completo (gratuito o de pago) 3109/10520295.2012.758779

AUTORES / AUTHORS:  - Yildiz H; Oztas H; Yildiz D; Koc A; Kalipci E

INSTITUCIÓN / INSTITUTION:  - Mustafa Kemal University , Faculty of Science, Department of Biology , Antakya.

RESUMEN / SUMMARY:  - We investigated short (6 months) and long (12 months) term inhibitory effects of  low (200 ppm) and high (400 ppm) dosages of acetylsalicylic acid (aspirin) on exocrine pancreatic carcinogenesis. It is known that exocrine pancreatic carcinogenesis can be detected by the presence of atypical acinar cell foci (AACF) in pancreas. We investigated possible inhibitory effects of acetylsalicylic acid in an azaserine-treated rat model. AACF were produced in rats by injection with azaserine according to previous studies. Our findings showed that the number, volume and diameter of pancreatic AACF were reduced after acetylsalicylic acid application. These observations suggest that acetylsalicylic acid may exert a protective effect against neoplastic development of pancreatic acinar cells in azaserine injected rats. Our findings corroborate reports in the  literature concerning the effects of aspirin in reducing neoplastic development.

 

----------------------------------------------------

[202]

TÍTULO / TITLE:  - Detection of hypoxia with 18F-fluoromisonidazole (18F-FMISO) PET/CT in suspected  or proven pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Jan;38(1):1-6. doi: 10.1097/RLU.0b013e3182708777.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182708777

AUTORES / AUTHORS:  - Segard T; Robins PD; Yusoff IF; Ee H; Morandeau L; Campbell EM; Francis RJ

INSTITUCIÓN / INSTITUTION:  - Nuclear Medicine Department/WA PET Service, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, Australia. Tatiana.segard@health.wa.gov.au

RESUMEN / SUMMARY:  - PURPOSE OF THE REPORT: Pancreatic carcinoma is known to demonstrate molecular features of hypoxia. The aim of this prospective pilot study is to analyze the hypoxia agent fluoromisonidazole (FMISO) using PET/CT in pancreatic carcinoma and to compare FMISO activity with glucose metabolism reflected by FDG. PATIENTS AND  METHODS: Ten patients with pancreatic carcinoma underwent FMISO and FDG PET scans. FMISO and FDG PET/CT scans were analyzed by 2 PET physicians. Regions of interest drawn on the FDG images were transposed to the FMISO images after study  coregistration. The FDG SUVmax was used to quantify metabolic activity and FMISO  SUVmax and tumor-to-background (muscle) ratio to quantify hypoxia. RESULTS: Seven patients were diagnosed with pancreatic adenocarcinoma. The remaining patients had a neuroendocrine tumor, poorly differentiated/sarcomatoid carcinoma, and mucinous neoplasm. Visual analysis demonstrated increased FMISO activity in 2 pancreatic adenocarcinomas. All patients, however, had increased FDG activity at  the tumor site. Mean FDG SUVmax was 6 (range: 3.8 to 9.5) compared to 2.3 for FMISO (range: 1 to 3.4). The 2 positive studies on visual analysis of FMISO did not correspond to the largest tumors, the studies with the highest FMISO or FDG SUVmax. There was no significant correlation between FMISO and FDG SUVmax values. CONCLUSIONS: The hypoxia imaging agent, FMISO, demonstrates minimal activity in pancreatic tumors. If FMISO PET/CT is to be included in clinical trial protocols  of hypoxia in pancreatic cancer, it would require correlation with other imaging  modalities to localize the tumor and allow semiquantitative analysis.

 

----------------------------------------------------

[203]

TÍTULO / TITLE:  - Pancreatic neuroendocrine tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Dis Mon. 2013 Jan;59(1):5-19. doi: 10.1016/j.disamonth.2012.10.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.disamonth.2012.10.002

AUTORES / AUTHORS:  - Muniraj T; Vignesh S; Shetty S; Thiruvengadam S; Aslanian HR

 

----------------------------------------------------

[204]

TÍTULO / TITLE:  - Phase II trial of capecitabine combined with thalidomide in second-line treatment of advanced pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreatology. 2012 Nov-Dec;12(6):475-9. doi: 10.1016/j.pan.2012.09.007. Epub 2012 Oct 6.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.pan.2012.09.007

AUTORES / AUTHORS:  - Shi SB; Wang M; Niu ZX; Tang XY; Liu QY

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Shang Dong Tumor Hospital, Jinan 250117, PR China.

RESUMEN / SUMMARY:  - BACKGROUND: To evaluate the efficacy and tolerability of capecitabine combined with thalidomide in patients with advanced pancreatic cancer (APC) who have previously received gemcitabine-based therapy. METHODS: A total of 31 patients were recruited prospectively in Shandong Tumor Hospital from May 2007 to April 2009. Capecitabine was offered to patients twice a day at a dose of 1250 mg/m(2)  for 14-day then followed by 7-day rest. Thalidomide was administered 100 mg/day without interruption until disease progression or occurrence of unacceptable toxicity. RESULTS: Two patients presented partial response (PR), 11 patients showed stable disease (SD) and eighteen patients presented progressive disease (PD). The median progression-free survival (PFS) was 2.7 months (95% confidence interval (CI), 2.4-3.3) and the median overall survival (OS) was 6.1 months (95%  CI, 5.3-6.9). In the subgroup analysis, PFS had a significant difference between  the serum CA19-9 level decreasing >25% and decreasing <25%, with 3.0 months (95%  CI, 2.5-3.6) and 2.5 months (95% CI, 1.8-3.2), (Log Rank = 0.02), respectively. Hematological toxicity included leukocytopenia, anemia and neutropenia. Non-hematological toxicities included diarrhea, skin rash, nausea/vomiting, hand-foot syndrome, fatigue, dizziness, drowsiness and constipation. CONCLUSION:  Capecitabine combined with thalidomide is a well-tolerated second-line regimen, in patients with APC refractory to gemcitabine.

 

----------------------------------------------------

[205]

TÍTULO / TITLE:  - Association Between KRAS Mutation, Detected in Pancreatic Cyst Fluid, and Long-term Outcomes of Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Gastroenterol Hepatol. 2012 Dec 23. pii: S1542-3565(12)01508-X. doi: 10.1016/j.cgh.2012.12.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cgh.2012.12.008

AUTORES / AUTHORS:  - Rockacy MJ; Zahid M; McGrath KM; Fasanella KE; Khalid A

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

RESUMEN / SUMMARY:  - BACKGROUND & AIMS: Endoscopic ultrasound (EUS) with fine-needle aspiration is routinely used to evaluate pancreatic cysts. We investigated the association between results from DNA analysis of cyst fluid and patient outcomes. METHODS: In a retrospective analysis, we collected data from 113 patients with pancreatic cysts who underwent EUS with fine-needle aspiration at a tertiary care center from June 2004-June 2007. Detailed follow-up data were obtained through October 2010 (mean, 47 months). Pancreatic cysts were categorized as non-benign or benign on the basis of pathology analysis of surgical samples and patients’ outcomes. We compared the patient characteristics, presenting symptoms, EUS imaging characteristics, and results from analysis of cyst fluid, including cytology results, levels of carcinoembryonic antigen, and DNA sequencing results. RESULTS: Fifty-one patients underwent pancreatic surgery (10 had malignant, 18 had mucinous, and 16 had benign cysts), 63 patients were followed long-term, and 13 patients died of pancreatic cancer. On the basis of multivariate regression analysis, the presence of cyst solid component, patient symptoms, cyst size >3 cm, and detection of KRAS mutations at codons 12 and 13 in cyst fluid were independently associated with a non-benign course. CONCLUSIONS: KRAS mutations, detected in pancreatic cyst fluid, are associated with mucinous cysts and progression and development of malignancy and should be considered in assessing pancreatic cysts. The presence of a cyst solid component, patient symptoms, and cyst size greater than 3 cm were additional high-risk factors for a malignant course of disease.

 

----------------------------------------------------

[206]

TÍTULO / TITLE:  - Quantitative real-time PCR expression analysis of peripheral blood mononuclear cells in pancreatic cancer patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:157-73. doi: 10.1007/978-1-62703-287-2_8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_8

AUTORES / AUTHORS:  - Baine MJ; Mallya K; Batra SK

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE, USA.

RESUMEN / SUMMARY:  - The ability of peripheral blood mononuclear cells (PBMCs) to act as a surrogate window into the presence and physiologic effects of pancreatic cancer is becoming increasingly apparent. In this chapter, we describe the techniques for isolation, lysis, RNA extraction, cDNA synthesis, and Q-RT PCR analysis of PBMCs as well as  reasonable alternatives and the advantages and disadvantages of each. We further  discuss the noteworthy considerations necessary for successful isolation and conversion of the high-quality PBMC RNA required to acquire interpretable and reproducible results for PBMC genetic expression analysis.

 

----------------------------------------------------

[207]

TÍTULO / TITLE:  - Growth inhibition of pancreatic cancer by experimental treatment with 4-phenylbutyrate is associated with increased expression of Connexin 43.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Res. 2012;20(2-3):103-11.

AUTORES / AUTHORS:  - Dovzhanskiy DI; Hartwig W; Lazar NG; Schmidt A; Felix K; Straub BK; Hackert T; Krysko DV; Werner J

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

RESUMEN / SUMMARY:  - Histone deacetylase inhibitors are a new and promising drug family with a strong  anticancer activity and potent modulation of connexin expression. The restoration of connexins in cancer cells has been suggested as a possible mechanism to control tumor progression. The aim of this study was to investigate the effects of 4-phenylbutyrate (4-PB) on the growth of human pancreatic cell lines in vitro  and in vivo with a focus on connexin modulation. The proliferation of tumor cells was determined using an MTT assay, and the effect of 4-PB in vivo was studied in  a chimeric mouse model. The expression and localization of connexin 43 (Cx43) were assessed by Western blot, immunofluorescence microscopy, and immunohistochemistry. Antitumoral activity was assessed by immunohistochemistry for Ki-67 and histone H4. Treatment with 4-PB resulted in the significant in vitro and in vivo growth inhibition of pancreatic tumor cells. The reduction of the xenograft tumor volume was associated with the inhibition of histone deacetylation and decrease in cell proliferation. Treatment with 4-PB caused a significant increase in the Cx43 expression in T3M4 cells (up to 2.8-fold). The newly synthesized Cx43 was localized in the cytoplasm but not on the cell membrane. Treatment with 4-PB inhibited the proliferation of human pancreatic tumor cells in vitro and in vivo and increased the expression of Cx43. Therefore, 4-PB might be useful in the therapy of pancreatic cancer.

 

----------------------------------------------------

[208]

TÍTULO / TITLE:  - Mutant TP53 in Duodenal Samples of Pancreatic Juice From Patients With Pancreatic Cancer or High-Grade Dysplasia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Gastroenterol Hepatol. 2012 Nov 28. pii: S1542-3565(12)01413-9. doi: 10.1016/j.cgh.2012.11.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cgh.2012.11.016

AUTORES / AUTHORS:  - Kanda M; Sadakari Y; Borges M; Topazian M; Farrell J; Syngal S; Lee J; Kamel I; Lennon AM; Knight S; Fujiwara S; Hruban RH; Canto MI; Goggins M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions.

RESUMEN / SUMMARY:  - BACKGROUND & AIMS: Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated wither mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer. METHODS: We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls. RESULTS: TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2 of 22), 17.8% of PanIN-2 (8 of 45), 38.1% of high-grade IPMNs (8 of 21), 47.6% of PanIN-3 (10 of 21), and 75% of invasive pancreatic adenocarcinomas (15 of 20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29 of 43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52-0.80) and 4 of 8 patients with  high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions. CONCLUSIONS: We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dysplasia. Clinical Trial numbers: NCT00438906 and NCT00714701.

 

----------------------------------------------------

[209]

TÍTULO / TITLE:  - Upregulation of Transgelin is an independent factor predictive of poor prognosis  in patients with advanced pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Sci. 2013 Jan 18. doi: 10.1111/cas.12107.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cas.12107

AUTORES / AUTHORS:  - Zhou L; Zhang R; Zhang L; Sun Y; Yao W; Zhao A; Li J; Yuan Y

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

RESUMEN / SUMMARY:  - Transgelin is a known actin-binding protein, which plays a role in regulating the functions of smooth muscle cells or fibroblasts. Recent evidence indicates that transgelin has been involved in diverse human cancers, yet its role in pancreatic cancer remains unclear. We therefore evaluated the expression characteristics and function of transgelin in pancreatic cancer. Immunohistochemical analysis of benign (n = 30 patients) and malignant (n = 114 patients) pancreatic ductal cells showed significantly higher transgelin staining in malignant cells. Lymph node metastasis (P=0.026) and diabetes (P = 0.041) were shown to significantly correlate with transgelin protein expression. Patients with high transgelin expression showed a shorter 5-year overall survival and a lower tumor-specific survival than those with low transgelin expression. Multivariate analysis revealed that transgelin was an independent factor affecting pancreatic tumor-specific survival (P=0.025). In vitro, RNA interference-mediated transgelin knockdown resulted in inhibition of pancreatic cancer cell proliferation, migration and invasion. Depletion of transgelin expression could suppress pancreatic tumorigenicity and tumor growth in vivo, and produce enhanced cytotoxic effects of gemcitabine on pancreatic cancer cells both in vitro and in  vivo. Our results indicate that transgelin plays a promoting role in tumor progression, and appears to be a novel prognostic marker for advanced pancreatic  cancer.

 

----------------------------------------------------

[210]

TÍTULO / TITLE:  - Insulinoma in a patient with type 2 diabetes mellitus proved at autopsy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocr Pract. 2012 Nov 1;18(6):1038.

AUTORES / AUTHORS:  - Kunieda T; Yamakita N; Yasuda K

INSTITUCIÓN / INSTITUTION:  - Department of General Internal Medicine, Matsunami General Hospital, Dendai 185-1 Kasamatsu-cho, Hashima-gun Gifu 501-6062, Japan.

 

----------------------------------------------------

[211]

TÍTULO / TITLE:  - The Role of Cytology in the Preoperative Assessment and Management of Patients with Pancreaticobiliary Tract Neoplasms.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Surg. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11605-012-2133-x

AUTORES / AUTHORS:  - Pang JC; Minter RM; Kwon RS; Simeone DM; Roh MH

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Michigan Health System, 1500 E. Medical Center Dr., 2G340, Ann Arbor, MI, 48109-5054, USA, jcpang@med.umich.edu.

RESUMEN / SUMMARY:  - OBJECTIVE: Endoscopic ultrasound-guided fine-needle aspiration and bile duct brushings are utilized in the cytologic evaluation of solid and cystic pancreaticobiliary tract lesions. We sought to determine the diagnostic accuracy  of cytology. METHODS: Five hundred seventy-nine pancreatic resections with 727 corresponding cytology specimens were identified from 1997 to 2012. Histologic diagnoses included benign, carcinoma, pancreatic endocrine neoplasm (PEN), nonepithelial neoplasms, cystic neoplasms, and ampullary adenomas. Standard interpretative categories-nondiagnostic, negative, atypical, suspicious, and positive-were utilized for preoperative cytology specimens. RESULTS: For solid masses, the sensitivity and specificity of positive fine-needle aspiration (FNA)  cytology for detecting carcinoma were 74 and 100 %, respectively. FNAs performed  better than brushings (sensitivity, 40 %; specificity, 98 %) in detecting carcinomas. Similar findings were seen for PENs and nonepithelial neoplasms. For  cystic lesions, the sensitivity of FNA for predicting malignancy was lower (24 %) with a specificity of 97 %. Sequentially combining suspicious and atypical categories with the positive category resulted in increases in sensitivity and decreases in specificity for all cases except for cystic lesions. CONCLUSIONS: Cytology adds to the assessment of solid masses, but its utility in cystic lesions is less clear. Consideration of a suspicious cytologic interpretation as  a positive diagnosis for triaging patients to surgery is supported by our study.

 

----------------------------------------------------

[212]

TÍTULO / TITLE:  - Very high concentration of d-dimers in portal blood in patients with pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pol Przegl Chir. 2012 Dec 1;84(10):521-5. doi: 10.2478/v10035-012-0087-z.

            ●● Enlace al texto completo (gratuito o de pago) 2478/v10035-012-0087-z

AUTORES / AUTHORS:  - Durczynski A; Szymanski D; Nowicki M; Hogendorf P; Poznanska G; Strzelczyk J

RESUMEN / SUMMARY:  - The aim of the study Nowadays, increasing attention has been focused on relation  between increased D-dimer levels and cancer among patients without detectable thrombosis. was to measure plasma D-dimer levels in portal and peripheral blood in pancreatic cancer patients with absence of venous thromboembolism. Material and methods. Fifteen consecutive patients hospitalized in the Department of General and Transplant Surgery of Medical University in Lodz, from January to March 2012 who underwent surgery due to a pancreatic cancer were enrolled. At laparotomy, portal and peripheral blood were sampled concurrently. D-dimer and fibrinogen levels were measured. Moreover, to investigate overall coagulation function prothrombin time (PT), prothrombin index (PI), international normalized  ratio (INR), thrombin time (TT), activated partial thromboplastin time (APTT), TT and APTT index were evaluated. Results. Peripheral plasma D-dimmer levels above normal range were found in 10/15 patients (66,67%), whereas D-dimer above normal  values were confirmed in all portal blood samples. Mean D-dimer values were higher in portal than in peripheral blood (3279.37 vs 824.64, by 297%, p=0,025).  These discrepancies were accompanied by normal limits of portal and peripheral levels of fibrinogen and comparable coagulation function indexes. Conclusion. Our preliminary study showed the close relation between activation of hemostasis, reflected by elevated D-dimers in portal blood and presence of pancreatic cancer. These data suggest that measurement of portal blood D-dimer levels may be a potentially useful technique for screening the pancreatic cancer.

 

----------------------------------------------------

[213]

TÍTULO / TITLE:  - Circadian Gene Expression and Clinicopathologic Correlates in Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Surg. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11605-012-2112-2

AUTORES / AUTHORS:  - Relles D; Sendecki J; Chipitsyna G; Hyslop T; Yeo CJ; Arafat HA

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Thomas Jefferson University, 1015 Walnut Street, Suite 618 Curtis, Philadelphia, PA, 19107, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: The circadian rhythm is responsible for physiologic homeostasis, behavior, and components of multiple metabolic processes. Disruption of the circadian rhythm is associated with cancer development, and several circadian clock genes have been implicated in loss of cell cycle control, impaired DNA damage repair, and subsequent tumor formation. Here, we investigated the expression profiles of several circadian clock genes in pancreatic ductal adenocarcinoma (PDA). METHODS: Quantitative real-time polymerase chain reaction was used to examine the circadian clock genes (brain-muscle-like (Bmal)-ARNTL, circadian locomotor output cycles kaput (Clock), cryptochrome 1 (Cry1), cryptochrome 2 (Cry2), casein kinase 1epsilon (CK1epsilon), period 1 (Per1), period 2 (Per2), period 3 (Per3), timeless (Tim), and timeless-interacting protein (Tipin)) in PDA, as well as matching adjacent and benign tissue. Logistic regression models with robust variance were used to analyze the gene expression levels, and Kaplan-Meier survival curves were generated based on gene expression. RESULTS: In the tumor tissue of PDA patients, compared to their matched adjacent  tissue, expression levels of all circadian genes were lower, with statistical significance for Per1, Per2, Per3, Cry1, Cry2, Tipin, Tim, CK1epsilon, Bmal-ARNTL, and Clock (p < 0.025). PDA tumors also expressed significantly lower  levels of the circadian genes when compared to benign lesions for Per1, Per2, Per3, Cry2, Tipin, and CK1epsilon. A significant association between low levels of expression in the tumors and reduced survival was found with Per1, Per2, Per3, Cry2, Tipin, CK1epsilon, Clock, and Bmal-ARNTL. CONCLUSIONS: Our results reveal for the first time a dysregulated transcription of several circadian genes in PDA. Elevation of the gene levels in the benign and matched adjacent tissues may  be indicative of their role during the process of tumorigenesis. The potential of using circadian genes as predictive markers of the outcomes and survival and distinguishing PDA from benign pancreas must be studied in larger populations to  validate and demonstrate their eventual clinical utility.

 

----------------------------------------------------

[214]

TÍTULO / TITLE:  - Safety and Effectiveness of Gemcitabine in 855 Patients with Pancreatic Cancer under Japanese Clinical Practice Based on Post-marketing Surveillance in Japan.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Jpn J Clin Oncol. 2013 Feb;43(2):139-45. doi: 10.1093/jjco/hys211. Epub 2012 Dec  28.

            ●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hys211

AUTORES / AUTHORS:  - Ioka T; Katayama K; Tanaka S; Takakura R; Ashida R; Kobayashi N; Taniai H

INSTITUCIÓN / INSTITUTION:  - *Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka 537-8511, Japan. ioka-ta@mc.pref.osaka.jp.

RESUMEN / SUMMARY:  - OBJECTIVE: When gemcitabine was approved as an anti-cancer drug, there were limited data for Japanese patients treated with gemcitabine. Generally, advanced  or metastatic pancreatic cancer patients experience poor prognosis and suffer from debilitating disease-related symptoms. Reports and information on gemcitabine use within a large patient pool will be beneficial to aid physicians. Therefore, this post-marketing surveillance was conducted as a non-interventional, observational study on the use of gemcitabine in a clinical practice setting in Japan. METHODS: Patients had no previous treatment with gemcitabine and were diagnosed with pancreatic cancer by an attending physician.  Patients were registered between May 2001 and December 2003 in Japan. The patients were treated with gemcitabine. Data such as patient background, treatment details, adverse events, tumor response, serum CA19-9 levels and drug-related symptom improvement were assessed. RESULTS: Of the 890 patients registered for the study, 855 were included in the analysis of gemcitabine for safety. Four hundred and forty-three (51.9%) patients reported drug-related adverse events, with 97 patients (11.4%) experiencing serious adverse events. The incidence of interstitial lung disease was 0.7% (six patients). Six hundred patients were evaluated for tumor response. The overall response rate was 6.0% and the disease control rate was 54.0%. CA19-9 decreased in 63.6% of the 335 evaluable patients, with a >/=75% decrease seen in 19.4% of the total group. Drug-related symptom improvement was observed in 27.0% of the 686 evaluable patients. CONCLUSIONS: This large-scale surveillance could confirm the safety of  gemcitabine for Japanese pancreatic cancer patients as well as elucidate the efficacy profile, measured by drug-related symptom improvement, for Japanese pancreatic cancer patients.

 

----------------------------------------------------

[215]

TÍTULO / TITLE:  - The prevention and genetics of pancreatic cancer: a programmatic approach.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:205-14. doi: 10.1007/978-1-62703-287-2_10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_10

AUTORES / AUTHORS:  - Lucas AL; Chang MM; Lipsyc MD; Frucht H

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Columbia University Medical Center, New York, NY, USA.

RESUMEN / SUMMARY:  - Pancreatic cancer (PC) is typically a fatal disease due to its rapid growth and the lack of early diagnostic -techniques. Because approximately 10% of PCs are attributable to a hereditary susceptibility, identifying and studying patients with a family history of PC or known genetic predisposition to PC can improve the prevention, diagnosis, and treatment of PC. A skilled team of study investigators, physicians, genetic counselors, and data managers must work with patients and families to confidentially store and organize data from PC patients  and high-risk patients. This data, collected in conjunction with patients’ tissue and blood specimens, will contribute to the understanding of the biology, etiology, and epidemiology of PC, and can ultimately improve screening and management for patients with an underlying hereditary predisposition to PC.

 

----------------------------------------------------

[216]

TÍTULO / TITLE:  - The Clinical Utility of CA 19-9 in Pancreatic Adenocarcinoma: Diagnostic and Prognostic Updates.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Mol Med. 2013 Jan 15.

AUTORES / AUTHORS:  - Poruk KE; Gay DZ; Brown K; Mulvihill JD; Boucher KM; Scaife CL; Firpo MA; Mulvihill SJ

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT  84132, USA. matt.firpo@hsc.utah.edu.

RESUMEN / SUMMARY:  - CA 19-9 and CEA are the most commonly used biomarkers for diagnosis and management of patients with pancreatic cancer. Since the original compendium by Steinberg in 1990, numerous studies have reported the use of CA 19-9 and, to a lesser extent, CEA in the diagnosis of pancreatic cancer. Here we update an evaluation of the accuracy of CA 19-9 and CEA, and, unlike previous reviews, focus on discrimination between malignant and benign disease instead of normal controls. In 57 studies involving 3,285 pancreatic carcinoma cases, the combined  sensitivity of CA 19-9 was 78.2% and in 37 studies involving 1,882 cases with benign pancreatic disease the specificity of CA 19-9 was 82.8%. From the combined analysis of studies reporting CEA, the sensitivity was 44.2% (1,324 cases) and the specificity was 84.8% (656 cases). These measurements more appropriately reflect the expected biomarker accuracy in the differential diagnosis of patients with periampullary diseases. We also present a summary of the use of CA 19-9 as a prognostic tool and evaluate CA 19-9 diagnostic and prognostic utility in a 10-year, single institution experience.

 

----------------------------------------------------

[217]

TÍTULO / TITLE:  - Targeting of MAPK-associated molecules identifies SON as a prime target to attenuate the proliferation and tumorigenicity of pancreatic cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer. 2012 Dec 10;11(1):88.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1476-4598-11-88

AUTORES / AUTHORS:  - Furukawa T; Tanji E; Kuboki Y; Hatori T; Yamamoto M; Shimizu K; Shibata N; Shiratori K

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Pancreatic cancer is characterized by constitutive activation of mitogen-activated protein kinase (MAPK). Activation of MAPK is associated with the upregulation of genes implicated in the proliferation and survival of pancreatic cancer cells. We hypothesized that knockdown of these MAPK-associated molecules could produce notable anticancer phenotypes. METHODS: A RNA interference-mediated knockdown screening of 78 MAPK-associated molecules previously identified was performed to find molecules specifically associated with proliferation of pancreatic cancer cells in vitro. Expression of an identified molecule in pancreatic cancer tissues was examined by immunohistochemistry. In vivo tumorigenicity of cancer cells with stable knockdown of the molecule was assayed by using xenograft models. Flow cytometry and live cell imaging were employed to assess an association of the molecule with cell cycle. RESULTS: The knockdown screening revealed that knockdown of SON, the  gene encoding SON, which is a large serine/arginine-rich protein involved in RNA  processing, substantially suppressed pancreatic cancer cell proliferation and survival in vitro and tumorigenicity in vivo. SON expression was higher in ductal adenocarcinomas than in cells of normal ducts and precursor lesions in pancreatic cancer tissues. Knockdown of SON induced G2/M arrest and apoptosis in cultured cancer cells. The suppressive effect of SON knockdown on proliferation was less pronounced in cultured normal duct epithelial cells. SON formed nuclear speckles  in the interphase of the cell cycle and dispersed in the cytoplasm during mitosis. Live cell imaging showed that SON diffusely dispersed in the early mitotic phase, accumulated in some foci in the cytoplasm in the late mitotic phase, and gradually reassembled into speckles after mitosis. CONCLUSION: These results indicate that SON plays a critical role in the proliferation, survival, and tumorigenicity of pancreatic cancer cells, suggesting that SON is a novel therapeutic molecular target for pancreatic cancer.

 

----------------------------------------------------

[218]

TÍTULO / TITLE:  - Polysaccharide-K (PSK) increases p21(WAF/Cip1) and promotes apoptosis in pancreatic cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreatology. 2012 Nov-Dec;12(6):467-74. doi: 10.1016/j.pan.2012.09.004. Epub 2012 Sep 23.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.pan.2012.09.004

AUTORES / AUTHORS:  - Rosendahl AH; Sun C; Wu D; Andersson R

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Clinical Sciences, Lund University, SE-221 84 Lund, Sweden.

RESUMEN / SUMMARY:  - BACKGROUND: Polysaccharide-K (PSK, Krestin(®)) is a natural remedy and one of the most commonly used medicinal mushroom extracts. It has been used as oral adjuvant treatment in cancer therapy in Japan and other Asian countries for more  than 40 years. PSK is thought to be an immune modulator, however, its antitumor actions remain undefined. The aim of the present study was to investigate underlying mechanisms by which PSK exerts its antitumor effects on malignant epithelial cells. METHODS: Antitumor activities of PSK were evaluated on multiple human pancreatic adenocarcinoma cells in vitro. Cell viability, apoptotic pathways, cytokine expression and involvement of TLR2 and TLR4 were monitored by  MTT, flow cytometry, Western blotting and protein arrays. RESULTS: We demonstrate that PSK acts as a growth inhibitor for pancreatic cancer cells, known otherwise  to be highly resistant to conventional chemotherapies. Pancreatic cancer cells can be protected against PSK-mediated growth inhibition by neutralizing antibodies against TLR2 and TLR4. The antiproliferative actions were associated with upregulated cell cycle regulatory p21(WAF/Cip1) and pro-apoptotic protein Bax levels, resulting in cell cycle arrest and induction of apoptosis. In addition, a significant growth inhibition and additive effect was observed with PSK and gemcitabine administered as combined treatment. CONCLUSION: While previous studies have emphasized the potential importance of PSK in immune activation, the present results uncover additional mechanisms on epithelial cells that may contribute to the antitumor effects provided by PSK as suggested by clinical observations.

 

----------------------------------------------------

[219]

TÍTULO / TITLE:  - Therapeutic effect of c-Jun N-terminal kinase inhibition on pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Sci. 2012 Dec 12. doi: 10.1111/cas.12080.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cas.12080

AUTORES / AUTHORS:  - Takahashi R; Hirata Y; Sakitani K; Nakata W; Kinoshita H; Hayakawa Y; Nakagawa H; Sakamoto K; Hikiba Y; Ijichi H; Moses HL; Maeda S; Koike K

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo.

RESUMEN / SUMMARY:  - c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase (MAPK) family, and it is reportedly involved in the development of several cancers. However, the role of JNK in pancreatic cancer has not been elucidated. We assessed t he involvement of JNK in the development of pancreatic cancer and investigated the therapeutic effect of JNK inhibitors on this deadly cancer. Small interfering RNAs against JNK or the JNK inhibitor SP600125 were used to examine the role of JNK in cellular proliferation and the cell cycles of pancreatic cancer cell lines. Ptf1a(cre/+) ;LSL-Kras(G12D/+) ;Tgfbr2(flox/flox) mice were treated with the JNK inhibitor to examine pancreatic histology and survival. The effect of JNK inhibition on tumor angiogenesis was also assessed using cell lines and murine pancreatic cancer specimens. JNK was frequently activated in human and murine pancreatic cancer in vitro and in vivo. Growth of human pancreatic cancer cell lines was suppressed by JNK inhibition through G1 arrest in the cell cycle with decreased cyclin D1 expression. In addition, oncogenic K-ras expression led to activation of JNK in pancreatic cancer cell lines. Treatment of Ptf1a(cre/+) ;LSL-Kras(G12D/+) ;Tgfbr2(flox/flox) mice with the JNK inhibitor decreased growth of murine pancreatic cancer and prolonged survival of the mice significantly. Angiogenesis was also decreased by JNK inhibition in vitro and in vivo. In conclusion, activation of JNK promotes development of pancreatic cancer, and JNK may be a potential therapeutic target for pancreatic cancer.

 

----------------------------------------------------

[220]

TÍTULO / TITLE:  - Interaction of the Sympathetic Nerve with Pancreatic Cancer Cells Promotes Perineural Invasion through the Activation of STAT3 Signaling.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer Ther. 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0809

AUTORES / AUTHORS:  - Guo K; Ma Q; Li J; Wang Z; Shan T; Li W; Xu Q; Xie K

INSTITUCIÓN / INSTITUTION:  - 1Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University.

RESUMEN / SUMMARY:  - Perineural invasion (PNI) is one of the most important causes of local recurrence and poor survival in pancreatic cancer. However, the exact mechanism of PNI is still not clear. In this study, we sought to identify the reciprocal signaling interactions between sympathetic nerves and pancreatic cancer cells and the underlying mechanisms. We used mouse dorsal root ganglia and pancreatic cancer cells co-cultured in vitro, cellular and molecular biology and animal models to evaluate the function of the sympathetic neurotransmitter norepinephrine (NE) in  PNI progression and pathogenesis. NE promoted PNI of pancreatic cancer cells and  increased levels of phosphorylated STAT3 in a concentration-dependent manner. NE-mediated activation of STAT3 was inhibited by blocking beta-adrenergic receptors (AR) and by blocking protein kinase A but not through blocking alpha-AR. Blocking STAT3 could inhibit NE-induced NGF, MMP2 and MMP9 expression and attenuate the migratory, invasive ability and PNI of pancreatic cancer cells. Furthermore, PNI of pancreatic cancer cells was blocked by treatment with a STAT3 phosphorylation inhibitor in vivo. These studies show that NE plays a critical role in pancreatic cancer PNI development and progression through the beta-AR/PKA/STAT3 signaling pathway. Reciprocal signaling interactions between the sympathetic nerves and pancreatic cancer cells critically contribute to pancreatic cancer PNI pathogenesis. Inhibition of the activity of sympathetic nerves or STAT3 may be potential strategies for pancreatic cancer PNI therapy.

 

----------------------------------------------------

[221]

TÍTULO / TITLE:  - Transmural endoscopic necrosectomy of infected pancreatic necroses and drainage of infected pseudocysts: A tailored approach.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Scand J Gastroenterol. 2013 Feb;48(2):231-40. doi: 10.3109/00365521.2012.752029.  Epub 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 3109/00365521.2012.752029

AUTORES / AUTHORS:  - Rische S; Riecken B; Degenkolb J; Kayser T; Caca K

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Klinikum Ludwigsburg , Posilipostrasse 4, 71640 Ludwigsburg , Germany.

RESUMEN / SUMMARY:  - Abstract Objective. Transmural endoscopic drainage and necrosectomy have become favored treatment modes for infected pancreatic pseudocysts and necroses. In this analysis, we summarize the outcome of 40 patients with complicated course of acute pancreatitis after endoscopic treatment. Material and methods. From January 2006 through May 2011, 40 patients of our department with complicated pancreatitis were included in this retrospective analysis. All patients underwent endosonographic transgastric puncture followed by wire-guided insertion of one or more double pigtail stents. Patients with extensive necroses were treated repeatedly with transgastric necrosectomy. Treatment success was determined by clinical, laboratory, and radiological parameters. Results. Nine patients had interstitial pancreatitis (IP) with pancreatic pseudocysts. Thirty-one patients had necrotizing pancreatitis (NP) with acute pancreatic necroses (n = 4) or walled-off pancreatic necrosis (n = 27). All patients with IP and nine patients with NP had pseudocysts without solid material and underwent transgastric drainage only. In this group major complications occurred in 11.1% and no mortality was observed. Twenty-two NP patients were treated with additional repeated necrosectomy. In patients with localized peripancreatic necroses (n = 10) no need of surgery or mortality was observed, major complications occurred in 10%. In patients with extensive necroses reaching the lower abdomen (n = 12), three needed subsequent surgery and three died. Conclusions. Transgastric endoscopy is an effective minimally invasive procedure even in patients with advanced pancreatic necroses. Complication rate is low particularly in patients with sole pseudocysts or localized necroses. The extent of the fluid collections  and necroses is a new predictive parameter for the outcome of the patients.

 

----------------------------------------------------

[222]

TÍTULO / TITLE:  - Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Mol Med. 2013 Jan 15.

AUTORES / AUTHORS:  - Yang J; Zhang Y; Cui X; Yao W; Yu X; Cen P; Hodges SE; Fisher WE; Brunicardi FC; Chen C; Yao Q; Li M

INSTITUCIÓN / INSTITUTION:  - The Vivian L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, Texas 77030, USA. Min.Li@uth.tmc.edu.

RESUMEN / SUMMARY:  - Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs  and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human  zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results  and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might  serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

 

----------------------------------------------------

[223]

TÍTULO / TITLE:  - Sphere-forming assays for assessment of benign and malignant pancreatic stem cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:281-90. doi: 10.1007/978-1-62703-287-2_15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_15

AUTORES / AUTHORS:  - Wang YJ; Bailey JM; Rovira M; Leach SD

INSTITUCIÓN / INSTITUTION:  - McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

RESUMEN / SUMMARY:  - Sphere-forming assays are an in vitro technique to assay both normal and neoplastic cells for clonogenic growth potential. Currently, the identification of adult progenitors in the pancreas remains an area of intense investigation. The use of sphere-forming assays provides a critical step to identify new cell types in the pancreas that are capable of clonogenic growth and differentiation.  In the field of cancer biology, cancer stem cells have been defined functionally  by two major criteria: their ability to undergo self-renewal and their ability to produce differentiated progeny, two conditions which satisfy the criteria of stem cells. Here we briefly review both the capabilities of pancreatosphere and pancreatic tumorsphere assays, discuss important caveats regarding their use, and provide detailed protocols for the assay of both normal and neoplastic cells.

 

----------------------------------------------------

[224]

TÍTULO / TITLE:  - The use of fluorescent probes in the study of reactive oxygen species in pancreatic cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:321-9. doi: 10.1007/978-1-62703-287-2_18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_18

AUTORES / AUTHORS:  - Dinnen RD; Mao Y; Fine RL

INSTITUCIÓN / INSTITUTION:  - Experimental Therapeutics Program, Division of Medical Oncology, Columbia University Medical Center, New York, NY, USA.

RESUMEN / SUMMARY:  - The use of fluorescent probes can be an easy and quick method to analyze whether  or not reactive oxygen species (ROS) are involved in a particular cellular process or the result of a particular drug treatment. ROS activate a variety of cell signaling and death pathways including apoptosis and necrosis (Raha and Robinson. Am J Med Gen 106:62-70, 2001). Here we describe a number of different probes, their specificities, advantages and limitations, as well as useful techniques important for their use.

 

----------------------------------------------------

[225]

TÍTULO / TITLE:  - Targeted Degradation of KRAS by an Engineered Ubiquitin Ligase Suppresses Pancreatic Cancer Cell Growth in vitro and in vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer Ther. 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0650

AUTORES / AUTHORS:  - Ma YH; Gu YM; Zhang Q; Han YQ; Yu SN; Lu ZH; Chen J

INSTITUCIÓN / INSTITUTION:  - 1Dept. of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.

RESUMEN / SUMMARY:  - KRAS is an attractive pancreatic ductal adenocarcinoma (PDAC) therapeutic target. E3 ligase is thought to be the component of the ubiquitin conjugation system that is directly responsible for substrate recognition. In this study, an engineered E3 ubiquitin ligase (RC-U) was generated to target the KRAS oncoprotein for ubiquitination and degradation. The engineered E3 ubiquitin ligases (RC-U) were constructed (pRC-U and lentivirus expressing RC-U). After transfecting the pRC-U  plasmid into human pancreatic cancer cells, KRAS expression levels were determined. KRAS expression was also evaluated in cells transfected with pRC-U and treated with MG-132 or cycloheximide. Interactions between RC-U and KRAS as well as whether RC-U could ubiquitinate KRAS were investigated. Extracellular signal-regulated protein kinase ½ (ERK1/2) and phosphorylated ERK ½ (pERK1/2) levels were examined in pancreatic cancer cells transfected with pRC-U. The effects of RC-U on pancreatic cancer cell growth were assessed. RC-U decreased KRAS protein levels. After pRC-U transfection, KRAS stability was increased in the presence of MG-132. HEK 293T cells were transfected with a mutant KRAS construct together with pRC-U and incubated with cycloheximide to inhibit new protein synthesis. The exogenous mutant KRAS oncoprotein was degraded more quickly. RC-U can bind KRAS, and KRAS can be ubiquitinated by RC-U. pERK1/2 protein levels were decreased. RC-U resulted in reduced cell proliferation in vitro and in vivo. KRAS destruction by RC-U occurs through a ubiquitin-dependent, proteasome-mediated degradation pathway. RC-U inhibited pancreatic cancer cell growth in vitro and in vivo.

 

----------------------------------------------------

[226]

TÍTULO / TITLE:  - Analysis of the potential for pancreatic cancer metastasis in vitro and in vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:301-19. doi: 10.1007/978-1-62703-287-2_17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_17

AUTORES / AUTHORS:  - Huang C; Xie K

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, Shanghai, PRChina.

RESUMEN / SUMMARY:  - Pancreatic cancer remains a challenging disease, with an overall 5-year survival  rate below 5%, the main reason being that it has an extremely high potential for  invasion and metastasis. This potential may contribute to the fact that in more than three fourths of patients diagnosed with pancreatic cancer, it has already spread locally and to distant organs, precluding curative resection. Therefore, improved understanding of the mechanisms underlying pancreatic cancer metastasis  is urgently needed. In this chapter, we describe our approaches to determining the metastatic potential of pancreatic cancer cells. Specifically, we report the  details of these approaches, including in vitro assays of migration, invasion, adhesion, and angiogenesis and in vivo models of liver and lung metastasis and angiogenesis.

 

----------------------------------------------------

[227]

TÍTULO / TITLE:  - Genetic susceptibility to pancreatic cancer and its functional characterisation:  The PANcreatic Disease ReseArch (PANDoRA) consortium.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Dig Liver Dis. 2013 Feb;45(2):95-9. doi: 10.1016/j.dld.2012.09.014. Epub 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.dld.2012.09.014

AUTORES / AUTHORS:  - Campa D; Rizzato C; Capurso G; Giese N; Funel N; Greenhalf W; Soucek P; Gazouli M; Pezzilli R; Pasquali C; Talar-Wojnarowska R; Cantore M; Andriulli A; Scarpa A; Jamroziak K; Delle Fave G; Costello E; Khaw KT; Heller A; Key TJ; Theodoropoulos G; Malecka-Panas E; Mambrini A; Bambi F; Landi S; Pedrazzoli S; Bassi C; Pacetti P; Piepoli A; Tavano F; di Sebastiano P; Vodickova L; Basso D; Plebani M; Fogar P; Buchler MW; Bugert P; Vodicka P; Boggi U; Neoptolemos JP; Werner J; Canzian F

INSTITUCIÓN / INSTITUTION:  - German Cancer Research Center (DKFZ), Heidelberg, Germany; See Appendix A. Electronic address: d.campa@dkfz.de.

RESUMEN / SUMMARY:  - Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n=86), chronic pancreatitis (n=272) and 3847 healthy controls have been collected. As a collective effort of  the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going.

 

----------------------------------------------------

[228]

TÍTULO / TITLE:  - Neoadjuvant Therapy for Potentially Resectable Pancreatic Cancer: An Emerging Paradigm?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Oncol Rep. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11912-012-0291-3

AUTORES / AUTHORS:  - Brunner TB

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Freiburg University, Robert-Koch-Str. 3, 79106, Freiburg, Germany, thomas.brunner@uniklinik-freiburg.de.

RESUMEN / SUMMARY:  - Although neoadjuvant chemoradiotherapy has been tested for more than two decades  and can be safely delivered to patients with non-metastatic pancreatic cancer, no randomised trials have been reported until now. Here we provide an overview of the first randomised trial in patients with potentially resectable cancer and of  the latest developments in neoadjuvant therapy for this group of patients. It is  necessary to continue to perform clinical trials in this field to accurately identify the effect on survival and quality of life in patients with potentially  resectable, borderline resectable and unresectable pancreatic cancer. Aspects of  imaging for restaging and clinical prognostic factors are also discussed given they will be useful instruments for future trials.

 

----------------------------------------------------

[229]

TÍTULO / TITLE:  - Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer: a phase 2 study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Surg. 2013 Jan;17(1):94-101. doi: 10.1007/s11605-012-2064-6. Epub  2012 Nov 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11605-012-2064-6

AUTORES / AUTHORS:  - Hardacre JM; Mulcahy M; Small W; Talamonti M; Obel J; Krishnamurthi S; Rocha-Lima CS; Safran H; Lenz HJ; Chiorean EG

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University Hospitals Seidman Cancer Center and Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106, USA, jeffrey.hardacre@UHhospitals.org.

RESUMEN / SUMMARY:  - BACKGROUND: Despite continued investigation, limited progress has been made in the adjuvant treatment of resected pancreatic cancer. Novel or targeted therapies are needed. METHODS: Multi-institutional, open-label, dose-finding, phase 2 trial evaluating the use of algenpantucel-L (NewLink Genetics Corporation, Ames, IA) immunotherapy in addition to chemotherapy and chemoradiotherapy in the adjuvant setting for resected pancreatic cancer (ClinicalTrials.gov identifier, NCT00569387). The primary outcome was 12-month disease-free survival. Secondary outcomes included overall survival and toxicity. RESULTS: Seventy patients were treated with gemcitabine and 5-fluorouracil-based chemoradiotherapy as well as algenpantucel-L (mean 12 doses, range 1-14). After a median follow-up of 21 months, the 12-month disease-free survival was 62 %, and the 12-month overall survival was 86 %. The most common adverse events were injection site pain and induration. CONCLUSIONS: The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A multi-institutional, phase 3 study is ongoing (ClinicalTrials.gov identifier, NCT01072981).

 

----------------------------------------------------

[230]

TÍTULO / TITLE:  - Pancreatic Neuroendocrine Tumors: Signal Pathways and Targeted Therapies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Mol Med. 2013 Jan 15.

AUTORES / AUTHORS:  - Peng L; Schwarz RE

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, UT Southwestern Medical Center, 5909 Harry Hines Boulevard, Dallas, TX 75390-9234, USA. lan.peng@utsouthwestern.edu.

RESUMEN / SUMMARY:  - Pancreatic neuroendocrine tumors (PNETs) are rare but are well understood to cover a broad spectrum of clinical presentation, tumor biology and prognosis. More than 60% of PNETs are diagnosed at advanced disease stage and are ineligible for surgical resection. Prior to 2011, streptozocin was the only approved agent for unresectable advanced PNETs. In recent years, breakthroughs in signal pathway research have led to the identification of new therapeutic targets and agents directed at the molecular level. In 2011, two new targeted therapeutic agents, sunitinib and everolimus, were approved by the Food and Drug Administration (FDA). Sunitinib is an inhibitor of multiple tyrosine kinases, and everolimus is  an inhibitor of the mammalian target of rapamycin (mTOR) pathway. This review discusses the major signaling pathways that are frequently mutated or deregulated in PNETs, and the implications of molecular alterations for PNET therapy. Biologic therapy through targeting relevant pathways represents a promising approach in the therapy of advanced and unresectable PNETs.

 

----------------------------------------------------

[231]

TÍTULO / TITLE:  - Designing and Developing S100P Inhibitor 5-methyl Cromolyn (C5OH) for Pancreatic  Cancer Therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer Ther. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0771

AUTORES / AUTHORS:  - Arumugam T; Ramachandran V; Maxwell D; Bornmann WG; Logsdon CD

INSTITUCIÓN / INSTITUTION:  - 1Cancer Biology, The University of Texas MD Anderson Cancer Center.

RESUMEN / SUMMARY:  - We have previously shown that the anti-allergic drug cromolyn blocks S100P interaction with its receptor RAGE and improves gemcitabine effectiveness in pancreatic ductal adenocarcinoma (PDAC). However, the concentration required to achieve its effectiveness was high (100muM). In this current study, we designed and synthesized analogs of cromolyn and analyzed their effectiveness compared to  the parent molecule. An ELISA was used to confirm the binding of S100P with RAGE  and to test the effectiveness of the different analogs. Analog 5-methyl cromolyn  (C5OH) blocked S100P binding as well as the increases in NFkappaB activity, cell  growth and apoptosis normally caused by S100P. In vivo C5OH systemic delivery reduced NFkappaB activity to a greater extent than cromolyn and at ten times lesser dose (50mg vs 5mg). Treatment of mice bearing syngeneic PDAC tumors showed that C5OH treatment reduced both tumor growth and metastasis. C5OH treatment of nude mice bearing orthotopic highly aggressive pancreatic Mpanc96 cells, increased the overall animal survival. Therefore, the cromolyn analog, C5OH, was  found to be more efficient and potent than cromolyn as a therapeutic for PDAC.

 

----------------------------------------------------

[232]

TÍTULO / TITLE:  - Role of alpha-gal epitope/anti-Gal antibody reaction in immunotherapy and its clinical application in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Sci. 2012 Dec 15. doi: 10.1111/cas.12084.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cas.12084

AUTORES / AUTHORS:  - Tanemura M; Miyoshi E; Nagano H; Eguchi H; Taniyama K; Kamiike W; Mori M; Doki Y

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure, Hiroshima, 737-0023, Japan; Surgery, Gastroenterological Surgery, Osaka University Graduate School of Medicine.

RESUMEN / SUMMARY:  - Pancreatic cancer is one of the commonest causes of death from cancer. Despite the availability of various treatment modalities, such as surgery, chemotherapy,  and radiotherapy, the 5-year survival remains poor. Although gemcitabine-based chemotherapy is typically offered as the standard care, most patients do not survive longer than 6 months. Therefore, new therapeutic approaches are needed. The alpha-gal epitope (Galalpha1-3Galbeta1-4GlcNAc-R) is abundantly synthesized from glycoproteins and glycolipids in non-primate mammals and New World monkeys,  but is absent in humans, apes and Old World monkeys. Instead, they produce anti-Gal antibody (Ab) (forming about 1% of circulating immunoglobulins), which specifically interacts with alpha-gal epitopes. Anti-Gal Ab can be exploited in cancer immunotherapy as vaccines that target antigen presenting cells (APC) to increase their immunogenicity. Tumor cells or tumor cell membranes from pancreatic cancer are processed to express alpha-gal epitopes. Subsequent vaccination with such processed cell membranes result in in vivo opsonization by  anti-Gal IgG in cancer patients. The interaction of the Fc portion of the vaccine-bound anti-Gal with Fcgamma receptors of APC induces effective uptake of  the vaccinating tumor cell membranes by the APC, followed by effective transport  of the vaccinating tumor membranes to the regional lymph nodes, and processing and presentation of the tumor-associated antigens (TAAs). Activation of tumor-specific B and T cells could elicit an immune response that in some patients is potent enough to eradicate the residual cancer cells that remain after completion of standard therapy. This review addresses these topics and new  avenues of clinical importance related to this unique antigen/antibody system (alpha-gal epitope/anti-Gal Ab) and advances in immunotherapy in pancreatic cancer.

 

----------------------------------------------------

[233]

TÍTULO / TITLE:  - Towards a clinical use of miRNAs in pancreatic cancer biopsies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Rev Mol Diagn. 2013 Jan;13(1):31-4. doi: 10.1586/erm.12.136.

            ●● Enlace al texto completo (gratuito o de pago) 1586/erm.12.136

AUTORES / AUTHORS:  - Frampton AE; Gall TM; Castellano L; Stebbing J; Jiao LR; Krell J

INSTITUCIÓN / INSTITUTION:  - HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London, W12 0HS, UK.

RESUMEN / SUMMARY:  - Evaluation of: Ali S, Saleh H, Sethi S, Sarkar FH, Philip PA. MicroRNA profiling  of diagnostic needle aspirates from patients with pancreatic cancer. Br. J. Cancer 107(8), 1354-1360 (2012). Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, despite advances in imaging, surgery and a greater understanding of its molecular biology. Patient outcomes remain poor due to an inability to detect disease early and resistance to anticancer treatments. miRNAs are promised to become ideal cancer biomarkers, as they are tumor and tissue specific and also incredibly stable molecules. So far, large profiling studies of the PDAC miRNome have identified the ‘usual suspects’ known to be deregulated in  solid tumors, such as oncomiR-21, as well as others that could be more robust for differentiating malignant from benign pancreatic disease. However, many of these  are yet to be validated clinically. The paper under evaluation provides further evidence for the use of miRNAs as diagnostic biomarkers for PDAC. We have reviewed the use of miRNAs as diagnostic analytes for detecting PDAC in biopsies.

 

----------------------------------------------------

[234]

TÍTULO / TITLE:  - 18-Fluorodeoxyglucose Positron Emission Tomography Does Not Aide in Diagnosis of  Pancreatic Ductal Adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Gastroenterol Hepatol. 2013 Jan 22. pii: S1542-3565(13)00091-8. doi: 10.1016/j.cgh.2012.12.033.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cgh.2012.12.033

AUTORES / AUTHORS:  - Matsumoto I; Shirakawa S; Shinzeki M; Asari S; Goto T; Ajiki T; Fukumoto T; Kitajima K; Ku Y

INSTITUCIÓN / INSTITUTION:  - Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine. Electronic address: imatsu@med.kobe-u.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND & AIMS: There are no accurate and reliable tools for diagnosis of early-stage pancreatic ductal adenocarcinoma (PDA) or small metastatic lesions. It is also a challenge to differentiate PDA from focal mass-forming pancreatitis  (FMP). There is controversy over the efficacy of 18-fluorodeoxyglucose positron-emission tomography (FDG-PET) in diagnosis of PDA. We investigated whether FDG-PET provides information that, combined with data from other imaging  techniques, can aide in decision making for patients with suspected PDA. METHODS: We performed a retrospective analysis of data collected from 232 consecutive patients with suspected PDA at Kobe University Hospital from January 2006 through June 2012. All patients underwent a diagnostic imaging protocol that included multi-detector row computed tomography (MDCT), super-paramagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), and FDG-PET. Based on endoscopic ultrasonography, fine-needle aspiration biopsy, or endoscopic retrograde cholangiopancreatography analyses, 218 patients had PDA (89 underwent  resection and 129 did not) and 14 had FMP (8 had focal mass-forming chronic pancreatitis [FMCP] and 6 had focal mass-forming autoimmune pancreatitis [(FMAIP]). RESULTS: FDG-PET detected 50% of stage 0 and I, 91.9% of stage II, 100% of stage III, and 96.8% of stage IV tumors. Detection was significantly affected by tumor size (P =.024) and T stage (P =.023) in resected tumors. MDCT and SPIO-MRI detected significantly more liver metastases than FDG-PET. Few para-aortic lymph node or peritoneal metastases were detected by FDG-PET. FDG-PET correctly identified 11 of the 14 patients with FMP (5/8 with FMCP and 6/6 with FMAIP). CONCLUSIONS: FDG-PET is not effective in detecting early-stage PDA and small metastases, or in differentiating PDA from FMP. Combining FDG-PET with current diagnostic techniques for PDA did not provide any decisive information, so it should not be included in this analysis.

 

----------------------------------------------------

[235]

TÍTULO / TITLE:  - Glucagon-like peptide-1 receptor imaging with [Lys(40)(Ahx-HYNIC- (99m)Tc/EDDA)NH (2)]-exendin-4 for the detection of insulinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-012-2299-1

AUTORES / AUTHORS:  - Sowa-Staszczak A; Pach D; Mikolajczak R; Macke H; Jabrocka-Hybel A; Stefanska A; Tomaszuk M; Janota B; Gilis-Januszewska A; Malecki M; Kaminski G; Kowalska A; Kulig J; Matyja A; Osuch C; Hubalewska-Dydejczyk A

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Jagiellonian University Medical College, Kopernika 17, 31-501, Cracow, Poland, sowiana@gmail.com.

RESUMEN / SUMMARY:  - PURPOSE: The objective of this article is to present a new method for the diagnosis of insulinoma with the use of [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH(2)]-exendin-4. METHODS: Studies were performed in 11 patients with negative results of all available non-isotopic diagnostic methods (8 with symptoms of insulinoma, 2 with malignant insulinoma and 1 with nesidioblastosis). In all patients glucagon-like peptide-1 (GLP-1) receptor imaging (whole-body and single photon emission computed tomography/CT examinations) after the injection of 740 MBq of the tracer was performed. RESULTS: Both sensitivity and specificity of GLP-1 receptor imaging were assessed to be 100 % in patients with benign insulinoma. In all eight cases with suspicion of insulinoma a focal uptake in the pancreas was found. In six patients surgical  excision of the tumour was performed (type G1 tumours were confirmed histopathologically). In one patient surgical treatment is planned. One patient was disqualified from surgery. In one case with malignant insulinoma pathological accumulation of the tracer was found only in the region of local recurrence. The  GLP-1 study was negative in the other malignant insulinoma patient. In one case with suspicion of nesidioblastosis, a focal accumulation of the tracer was observed and histopathology revealed coexistence of insulinoma and nesidioblastosis. CONCLUSION: [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH(2)]-exendin-4 seems to be a promising diagnostic tool in the localization of small insulinoma tumours, but requires verification in a larger series of patients.

 

----------------------------------------------------

[236]

TÍTULO / TITLE:  - N0/N1, PNL, or LNR? The Effect of Lymph Node Number on Accurate Survival Prediction in Pancreatic Ductal Adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Surg. 2013 Feb;17(2):257-66. doi: 10.1007/s11605-012-1974-7. Epub  2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11605-012-1974-7

AUTORES / AUTHORS:  - Valsangkar NP; Bush DM; Michaelson JS; Ferrone CR; Wargo JA; Lillemoe KD; Fernandez-Del Castillo C; Warshaw AL; Thayer SP

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and Andrew L. Warshaw, M.D., Institute for Pancreatic Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: We evaluated the prognostic accuracy of LN variables (N0/N1), numbers of positive lymph nodes (PLN), and lymph node ratio (LNR) in the context  of the total number of examined lymph nodes (ELN). METHODS: Patients from SEER and a single institution (MGH) were reviewed and survival analyses performed in subgroups based on numbers of ELN to calculate excess risk of death (hazard ratio, HR). RESULTS: In SEER and MGH, higher numbers of ELN improved the overall  survival for N0 patients. The prognostic significance (N0/N1) and PLN were too variable as the importance of a single PLN depended on the total number of LN dissected. LNR consistently correlated with survival once a certain number of lymph nodes were dissected (>/=13 in SEER and >/=17 in the MGH dataset). CONCLUSIONS: Better survival for N0 patients with increasing ELN likely represents improved staging. PLN have some predictive value but the ELN strongly  influence their impact on survival, suggesting the need for a ratio-based classification. LNR strongly correlates with outcome provided that a certain number of lymph nodes is evaluated, suggesting that the prognostic accuracy of any LN variable depends on the total number of ELN.

 

----------------------------------------------------

[237]

TÍTULO / TITLE:  - Adherence to pancreatic enzyme supplementation in adolescents with cystic fibrosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Can J Diet Pract Res. 2012 Winter;73(4):196-9.

AUTORES / AUTHORS:  - Faulkner C; Taper LJ; Scott M

INSTITUCIÓN / INSTITUTION:  - Department of Applied Human Nutrition, Mount Saint Vincent University, Halifax, NS.

RESUMEN / SUMMARY:  - PURPOSE: Levels of adherence to pancreatic enzyme supplementation were investigated in Atlantic Canada adolescents with cystic fibrosis (CF). METHODS: Participants were recruited from CF clinics at the Izaak Walton Killam Health Centre in Halifax, Nova Scotia, and the Janeway Children’s Health & Rehabilitation Centre in St. John’s, Newfoundland and Labrador. Self-report questionnaires were mailed to potential participants (n=51) by clinic staff and completed surveys (n=9) were mailed to the principal investigator. RESULTS: Nine  adolescents (mean age 15.2 +/- 1.9 years) participated in the study. The adherence survey indicated that the majority perceived themselves to be adherent  to taking enzymes with meals (67%), but only 44% perceived themselves to be adherent to taking enzymes with snacks. Recorded amounts of enzymes, taken over three days, indicated that 67% of participants were actually adherent to taking enzymes with meals and 56% with snacks. Including those who correctly predicted non-adherence, 56% and 44% of participants accurately predicted their adherence to taking enzymes with meals and snacks, respectively. CONCLUSIONS: Adherence rates in the literature vary because of differences in definition and measurement. In the CF population, adherence has been shown to have a positive effect on quality of life. Results for this small group of patients suggest that  Atlantic Canada adolescents with CF are able to estimate correctly their adherence to taking pancreatic enzymes, but definite conclusions cannot be made because of the small number of respondents.

 

----------------------------------------------------

[238]

TÍTULO / TITLE:  - Biliary Findings Assist in Predicting Enlargement of Intraductal Papillary Mucinous Neoplasms of the Pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Gastroenterol Hepatol. 2012 Dec 4. pii: S1542-3565(12)01427-9. doi: 10.1016/j.cgh.2012.11.027.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cgh.2012.11.027

AUTORES / AUTHORS:  - Matsuzaki J; Suzuki H; Okuda S; Tanimoto A; Asakura K; Fukuhara S; Okada S; Hirata K; Mori H; Masaoka T; Higuchi H; Hozawa S; Kuribayashi S; Takebayashi T; Hibi T

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

RESUMEN / SUMMARY:  - BACKGROUND & AIMS: There is controversy over the optimal management strategy for  patients with branch-duct type intraductal papillary mucinous neoplasms of the pancreas (BD-IPMN), precursors to pancreatic cancer. We aimed to identify factors associated with the presence of BD-IPMN and changes in their diameter. METHODS: Two separate analyses were conducted in a cohort of patients who underwent magnetic resonance cholangiopancreatography (MRCP) in a single year (2006). MRCP  findings and clinical outcomes of these patients were followed for a maximum of 6 years. We evaluated initial MRCP findings and demographics associated with the presence of BD-IPMN at baseline, and increase in BD-IPMN diameter over time. RESULTS: Over the follow-up period, 154 patients developed BD-IPMN and 322 patients did not. Older age, diabetes mellitus, gallbladder adenomyomatosis, and  absence of gallstones were associated with the presence of BD-IPMN at baseline. Increases in diameter of BD-IPMNs were associated with 3 baseline factors: BD-IPMN diameter greater than 17 mm, gallbladder adenomyomatosis, and a common bile duct (CBD) diameter less than 5.5 mm. Patients with BD-IPMN could be stratified into 4 groups with varying risk for the enlargement of BD-IPMN over time: those with 3 risk factors (hazard ratio [HR] 11.4; 95% confidence interval  [CI], 3.4-37.8), 2 risk factors (HR 4.7; 95% CI, 1.7-12.8), or 1 risk factor (HR  3.1; 95% CI, 1.2-8.2) compared to those without risk factors. CONCLUSIONS: For patients with BD-IPMN, careful follow-up evaluation is particularly important for those with BD-IPMN>17 mm in size, CBD diameter <5.5 mm, or gallbladder adenomyomatosis.

 

----------------------------------------------------

[239]

TÍTULO / TITLE:  - Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Med. 2012 Oct;1(2):207-17. doi: 10.1002/cam4.27. Epub 2012 Aug 16.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cam4.27

AUTORES / AUTHORS:  - Arcaroli J; Quackenbush K; Dasari A; Powell R; McManus M; Tan AC; Foster NR; Picus J; Wright J; Nallapareddy S; Erlichman C; Hidalgo M; Messersmith WA

INSTITUCIÓN / INSTITUTION:  - University of Colorado Cancer Center Denver, Colorado.

RESUMEN / SUMMARY:  - Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used.  Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] “top scoring pairs” polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3’  untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible.

----------------------------------------------------

[240]

TÍTULO / TITLE:  - Robotic-Assisted Minimally Invasive Central Pancreatectomy: Technique and Outcomes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Surg. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11605-012-2137-6

AUTORES / AUTHORS:  - Abood GJ; Can MF; Daouadi M; Huss HT; Steve JY; Ramalingam L; Stang M; Bartlett DL; Zeh HJ 3rd; Moser AJ

INSTITUCIÓN / INSTITUTION:  - Division of Surgical Oncology, Department of Surgery, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL, 60153, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Central pancreatectomy is a definitive treatment for low-grade tumors of the pancreatic neck that preserves pancreatic and splenic function at the potential expense of postoperative pancreatic fistula. We analyzed outcomes after robot-assisted central pancreatectomy (RACP) to reexamine the risk-benefit profile in the era of minimally invasive surgery. METHODS: Retrospective analysis of nine RACP performed between August 2009 through June 2010 at a single institution. RESULTS: The average age of the cohort was 64 (range 18-75 years) with six women (67 %). Indications for surgery included: five benign cystic neoplasm and four pancreatic neuroendocrine tumor. Median operative time was 425  min (range 305-506 min) with 190 ml median blood loss (range 50-350 ml) and one conversion to open due to poor visualization. Median tumor size was 3.0 cm (range 1.9-6.0 cm); all patients achieved R0 status. Pancreaticogastrostomy was performed in seven cases and pancreaticojejunostomy in two. The median length of  hospital stay was 10 days (range 7-19). Two clinically significant pancreatic fistulae occurred with one requiring percutaneous drainage. No patients exhibited worsening diabetes or exocrine insufficiency at the 30-day postoperative visit. CONCLUSIONS: RACP can be performed with safety and oncologic outcomes equivalent  to published open series. Although the rate of pancreatic fistula was high, only  22 % had clinically significant events, and none developed worsening pancreatic endocrine or exocrine dysfunction.

 

----------------------------------------------------

[241]

TÍTULO / TITLE:  - An interesting case of isolated pancreatic teratoma: lessons to learn.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Ter. 2012 Nov;163(6):495-7.

AUTORES / AUTHORS:  - Razman J; Azlanudin A; Eyad AJ; Zahiah M; Das S

INSTITUCIÓN / INSTITUTION:  - Departments of Surgery, and Radiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia;  Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abd Aziz, 56000, Kuala Lumpur, Malaysia.

RESUMEN / SUMMARY:  - Mature cystic teratomas of the pancreas are extremely rare tumours encountered in day-to-day clinical practice. Only few cases have been reported to date involving all age groups. The management, diagnosis and evaluation of this tumor are questionable, with definitive diagnosis taking place intra-operatively. We hereby report the case in a 30 year-old-male who presented with newly diagnosed diabetes mellitus and during the follow up he was noted to have elevated liver enzymes clinically, he was asymptomatic. The computerized tomography revealed a retropancreatic mass and pushing the mesenteric veins anteriorly. The mass was hypodense in nature and there was presence of calcification. Although the patient was asymptomatic, the decision for resecting the mass was made in view of the size and possibility of malignancy. In conclusion, considering the size and approximity of the mass to the pancreas, Whipple procedure’s is the most appropriate approach although the histological diagnosis has not been established preoperatively. Clin Ter 2012; 163(6):495-497.

 

----------------------------------------------------

[242]

TÍTULO / TITLE:  - The Prognostic Influence of Resection Margin Clearance Following Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Surg. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11605-012-2131-z

AUTORES / AUTHORS:  - Jamieson NB; Chan NI; Foulis AK; Dickson EJ; McKay CJ; Carter CR

INSTITUCIÓN / INSTITUTION:  - West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, UK, nigel.jamieson@glasgow.ac.uk.

RESUMEN / SUMMARY:  - INTRODUCTION: The poor overall survival associated with pancreatic ductal adenocarcinoma (PDAC) despite complete resection suggests that occult metastatic  disease is present in most at the time of surgery. Resection margin involvement (R1) following resection is an established poor prognostic factor. However, the definition of an R1 resection varies and the impact of margin clearance on outcome has not been examined in detail. METHODS: In a cohort of 217 consecutive  patients who underwent pancreaticoduodenectomy for PDAC with curative intent at a single institution between 1996 and 2011, the prognostic significance of the proximity of margin clearance was investigated. Microscopic margin clearance was  stratified by 0.5 mm increments from tumor present at the margin to >2.0 mm. Groups were dichotomized into clear and involved groups according to the different R1 definitions. Multivariate survival analysis was used to establish independent prognostic factors. RESULTS: For the 38 patients (17.5 %) where the tumor was >1.5 mm from the closest involved margin, there was a significantly prolonged overall median survival (63.1 months; 95 % confidence interval, 32.5-93.8) compared to R1 resections (16.9 months; 95 % confidence interval, 14.5-19.4; P < 0.0001, log-rank test). This cutoff represented the optimum distance for predicting long-term survival. As margin clearance increased, R1 status became a more powerful independent predictor of outcome; however, margin clearance did not relate to site of tumor recurrence. CONCLUSION: These data demonstrate that margin clearance by at least 1.5 mm identifies a subgroup of patients which may potentially achieve long-term survival. This study further confirms the need to achieve standardization across pancreatic specimen reporting. Stratification of patients into future clinical trials based upon the  degree of margin clearance may identify those patients likely to benefit from adjuvant therapy.

 

----------------------------------------------------

[243]

TÍTULO / TITLE:  - Borderline resectable pancreatic cancer: pushing the technical limits of surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Bull Am Coll Surg. 2013 Jan;98(1):61-3.

AUTORES / AUTHORS:  - Katz MH; Ahmad S; Nelson H

INSTITUCIÓN / INSTITUTION:  - mhgkatz@mdanderson.org

 

----------------------------------------------------

[244]

TÍTULO / TITLE:  - Up-regulation of MBD1 Promotes Pancreatic Cancer Cell Epithelial-Mesenchymal Transition and Invasion by Epigenetic Down-regulation of E-cadherin.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Mol Med. 2013 Jan 15.

AUTORES / AUTHORS:  - Xu J; Zhu W; Xu W; Yao W; Zhang B; Xu Y; Ji S; Liu C; Long J; Ni Q; Yu X

INSTITUCIÓN / INSTITUTION:  - Department of Pancreas and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China, 270 Dong An Road, Shanghai 200032, China. yuxianjun88@hotmail.com.

RESUMEN / SUMMARY:  - Methyl-CpG binding domain protein 1 (MBD1) has been implicated in transcriptional regulation, heterochromatin formation, genomic stability, cell-cycle progression  and development. It is also predicted that MBD1 might be involved in tumor development and progression. However, whether and how MBD1 is involved in tumorigenesis, especially in pancreatic cancer (PC), is currently unknown. We found that MBD1 was significantly up-regulated in PC tissues compared with the surrounding normal tissues according to RT-PCR data. Tissue microarray (TMA) based immunohistochemical study from 58 surgically resected PC specimens indicated that higher MBD1 expression correlated with lymph node metastasis and poor survival in PC patients. Gain- and loss-of-function studies in vitro validated MBD1 as a potent oncogene promoting PC cell invasion as well as epithelial-mesenchymal transition (EMT). Mechanistically, MBD1 is associated with Twist and NAD-dependent deacetylase sirtuin-1 (SIRT1), thereby forming the Twist-MBD1-SIRT1 complex on the CDH1 promoter, which resulted in reduced E-cadherin transcription activity and increased cell EMT ability. Significantly,  targeting MBD1 reversed the EMT phenotype of PC and restored sensitivity to chemotherapy. Taken together, the results of our study revealed a novel function  of MBD1 in PC invasion and metastasis by providing a molecular mechanism underlying MBD1-promoted EMT. Thus MBD1 may serve as a potential therapeutic target for PC.

 

----------------------------------------------------

[245]

TÍTULO / TITLE:  - Molecular characteristics of a pancreatic adenocarcinoma associated with Shwachman-Diamond syndrome.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Blood Cancer. 2013 Jan 9. doi: 10.1002/pbc.24453.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pbc.24453

AUTORES / AUTHORS:  - Dhanraj S; Manji A; Pinto D; Scherer SW; Favre H; Loh ML; Chetty R; Wei AC; Dror Y

INSTITUCIÓN / INSTITUTION:  - Cell Biology Program, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

RESUMEN / SUMMARY:  - BACKGROUND: Shwachman-Diamond syndrome (SDS) is characterized by hypoplasia of the bone marrow and exocrine pancreas and a high risk of leukemia. It is unknown  whether solid tumors are part of the disease phenotype. PROCEDURE: We performed copy number alterations using Affymetrix human SNP 6.0 array. Furthermore, we did direct sequencing of pancreatic cancer-related genes and immunohistochemical expression of selective proteins. RESULTS: Among 41 patients with SDS who enrolled on the registry, we identified one male patient with a solid tumor: moderately differentiated pancreatic ductal adenocarcinoma. The tumor harbored 41 copy number alterations (CNAs) and had no regions of loss of heterozygosity (LOH). None of these CNAs were exclusive to the tumor. One copy of the tumor suppressor genes CTNNA3 and LGALS9C was lost in both the peripheral blood and tumor. Direct sequencing of TP53, KRAS, and NRAS revealed no mutations. Immunohistochemical staining for cyclin D1, E-cadherin, p53 MLH1 and MSH2 and beta-catenin, was similar to that seen in non-hereditary pancreatic cancer. CONCLUSIONS: Our case raises the possibility that solid tumors are associated with SDS, thereby broadening the clinical phenotype of the disease. The relatively young age at cancer diagnosis and the specific involvement of the pancreas make the possibility of an association with SDS likely. Similar to leukemia in SDS, the pancreatic cancer developed in hypoplastic tissues. This observation and the relative genomic stability of the tumor strengthen the hypothesis of improved adaptation of malignant clones among a population of disadvantaged cells as a mechanism for tumor expansion in SDS. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

 

----------------------------------------------------

[246]

TÍTULO / TITLE:  - Evaluating dietary compounds in pancreatic cancer modeling systems.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:225-48. doi: 10.1007/978-1-62703-287-2_12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_12

AUTORES / AUTHORS:  - Mascarinas E; Eibl G; Grippo PJ

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

RESUMEN / SUMMARY:  - With the establishment of outstanding rodent models of pancreatic neoplasia and cancer, there are now systems available for evaluating the role diet, dietary supplements, and/or therapeutic compounds (which can be delivered in the diet) play in disease suppression. Several outstanding reports, which demonstrate clear inhibition or regression of pancreatic tumors following dietary manipulations, represent a noticeable advancement in the field by allowing for the contribution  of diet and natural and synthetic compounds to be identified. The real goal is to provide support for translational components that will provide true chemoprevention to individuals at higher risk for developing pancreatic cancer. In addition, administration of molecules with proven efficacy in an in vivo system will screen likely candidates for future clinical trials. Despite this growing enthusiasm, it is important to note that the mere one-to-one translation  of findings in rodent models to clinical outcomes is highly unlikely. Thus, careful consideration must be made to correlate findings in rodents with those in human cells with full disclosure of the subtle but often critical differences between animal models and humans. Additional concern should also be placed on the approaches employed to establish dietary components with real potential in the clinic.This chapter is focused on procedures that provide a systematic design for evaluating dietary compounds in cell culture and animal models to highlight which ones might have the greatest potential in people. The general format for this text is a stepwise use of fairly well-known approaches covered briefly but annotated with certain considerations for dietary studies. These methods include  administration of a compound or a diet, measuring the cellular and molecular effects (histology, proliferation, apoptosis, RNA and protein expression, and signaling pathways), measuring the level of certain metabolites, and assessing the stability of active compounds. Though this chapter is divided into in vitro and in vivo sections, it is not an implication as to the order of experiments but an endorsement for utilizing human cells to complement work in a rodent modeling  system. The notion that cell culture can provide the basis for further in vivo work is an attractive starting point, though the lack of a response in a single cell type should not necessarily prevent diet studies in rodents. The advantage of cell culture over animal models is the human origin of these cells and the ease and directness of manipulating a single cell type (particularly when exploring mechanism of action in that cell). Of course, the full effect of a diet, diet supplement, or therapeutic can only be wholly appreciated in an intact living organism with similar anatomical and physiological relevance. Thus, both approaches are considered in this chapter as each can provide unique strengths to determining the effectiveness of various dietary compounds or supplements on pancreatic neoplasia and cancer.

 

----------------------------------------------------

[247]

TÍTULO / TITLE:  - Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal  mechanism for initiation of pancreatic ductal adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Cell. 2012 Dec 11;22(6):737-50. doi: 10.1016/j.ccr.2012.10.025. Epub 2012  Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ccr.2012.10.025

AUTORES / AUTHORS:  - Kopp JL; von Figura G; Mayes E; Liu FF; Dubois CL; Morris JP 4th; Pan FC; Akiyama H; Wright CV; Jensen K; Hebrok M; Sander M

INSTITUCIÓN / INSTITUTION:  - Departments of Pediatrics and Cellular and Molecular Medicine, University of California-San Diego, La Jolla, CA 92093-0695, USA.

RESUMEN / SUMMARY:  - Tumors are largely classified by histologic appearance, yet morphologic features  do not necessarily predict cellular origin. To determine the origin of pancreatic ductal adenocarcinoma (PDA), we labeled and traced pancreatic cell populations after induction of a PDA-initiating Kras mutation. Our studies reveal that ductal and stem-like centroacinar cells are surprisingly refractory to oncogenic transformation, whereas acinar cells readily form PDA precursor lesions with ductal features. We show that formation of acinar-derived premalignant lesions depends on ectopic induction of the ductal gene Sox9. Moreover, when concomitantly expressed with oncogenic Kras, Sox9 accelerates formation of premalignant lesions. These results provide insight into the cellular origin of PDA and suggest that its precursors arise via induction of a duct-like state in acinar cells.

 

----------------------------------------------------

[248]

TÍTULO / TITLE:  - Development of orthotopic pancreatic tumor mouse models.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:215-23. doi: 10.1007/978-1-62703-287-2_11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_11

AUTORES / AUTHORS:  - Qiu W; Su GH

INSTITUCIÓN / INSTITUTION:  - Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.

RESUMEN / SUMMARY:  - Genetically engineered mouse models of pancreatic cancer that recapitulate human  pancreatic tumorigenesis have been established. However, the cost associated with generating and housing these mice can be -prohibitive. Tumor latency and progression to invasive diseases in these models are also highly variable. Xenograft mouse models of human pancreatic cancer including heterotopic and orthotopic have been widely used in preclinical studies for their comparatively low cost and rapid, predictable tumor growth. Of the two, orthotopic tumor mouse  models are preferred because they offer tissue site-specific pathology, allow studies of metastasis, and are generally deemed more clinically relevant. Here we describe the procedures of implanting cancer cell lines to generate orthotopic mouse models for pancreatic cancer.

 

----------------------------------------------------

[249]

TÍTULO / TITLE:  - Quantification of murine pancreatic tumors by high-resolution ultrasound.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:249-66. doi: 10.1007/978-1-62703-287-2_13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_13

AUTORES / AUTHORS:  - Sastra SA; Olive KP

INSTITUCIÓN / INSTITUTION:  - Herbery Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.

RESUMEN / SUMMARY:  - Ultrasonography is a powerful imaging modality that enables noninvasive, real-time visualization of abdominal organs and tissues. This technology may be adapted for use in mice through the utilization of higher frequency transducers,  allowing for extremely high-resolution imaging of the mouse pancreas. This technique is particularly well suited to pancreas imaging due to the ultrasonographic properties of the normal mouse pancreas, easily accessible imaging planes for the head and tail of the mouse pancreas, and the comparative difficulty in imaging the mouse pancreas with other technologies. A suite of measurement tools is available to characterize the normal and diseased states of  tissues. Of particular utility for cancer applications is the ability to use tomography to construct a 3D tumor volume, enabling longitudinal imaging studies  to track tumor development, or response to therapies.Here, we describe a detailed method for performing high-resolution ultrasound to detect and measure pancreatic lesions in a genetically engineered mouse model of pancreatic ductal using the VisualSonics Vevo2100 High Resolution Ultrasound System. The method includes preparation of the animal for imaging, 2D and 3D image acquisition, and post-acquisition analysis of tumor volumes. The combined procedure has been utilized extensively by our group and others for the preclinical evaluation of novel therapeutic agents in the treatment of pancreatic ductal adenocarcinoma (Olive et al., Science 324:1457-1461, 2009; Cook et al., Methods Enzymol 439:73-85, 2008; Singh et al., Nat Biotechnol 28:585-593, 2010; Beatty et al., Science 331:1612-1616, 2011).

 

----------------------------------------------------

[250]

TÍTULO / TITLE:  - Development of a cytokine-modified allogeneic whole cell pancreatic cancer vaccine.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:175-203. doi: 10.1007/978-1-62703-287-2_9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_9

AUTORES / AUTHORS:  - Laheru D; Biedrzycki B; Jaffee EM

INSTITUCIÓN / INSTITUTION:  - The Sidney Kimmel Cancer Center, the Skip Viragh Clinical Pancreatic Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA, Laherda@jhmi.edu.

RESUMEN / SUMMARY:  - Management of patients with pancreatic cancer is a multidisciplinary approach that presents enormous challenges to the clinician. Overall 5-year survival for all patients remains <3%. Symptoms of early pancreas cancer are nonspecific. As such, only a fraction of patients are candidates for surgery. While surgical resection provides the only curative option, most patients will develop tumor recurrence and die of their disease. To date, the clinical benefits of chemotherapy and radiation therapy have been important but have led to modest improvements. Tumor vaccines have the potential to specifically target the needle of pancreas cancer cells amidst the haystack of normal tissue. The discovery of pancreas tumor-specific antigens and the subsequent ability to harness this technology has become an area of intense interest for tumor immunologists and clinicians alike. Without knowledge of specific antigen targets, the whole tumor  cell represents the best source of immunizing antigens. This chapter will focus on the development of whole tumor cell vaccine strategies for pancreas cancer.

 

----------------------------------------------------

[251]

TÍTULO / TITLE:  - Identification and analysis of precursors to invasive pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:1-12. doi: 10.1007/978-1-62703-287-2_1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_1

AUTORES / AUTHORS:  - Matthaei H; Molin MD; Maitra A

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Oncology, The Sol Goldman Pancreatic Cancer Research  Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

RESUMEN / SUMMARY:  - Precursor lesions of pancreatic cancer have been recognized about a century ago.  The development of a consistent reproducible nomenclature and classification system for these lesions has been a major advance in the study of these noninvasive precursors. Pancreatic intraepithelial neoplasia (PanIN) as microscopic precursor lesions can be distinguished from mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMN) that are cystic and can often be recognized on imaging. Since precursor lesions harbor the unique chance to treat a patient before a fatal pancreatic cancer can arise a molecular  characterization is essential to understand the biology and to find diagnostic and therapeutic targets to fight this disease of near uniform lethality. In order to study precursor lesions on a molecular level a meticulous isolation of the neoplastic cells is inevitable. We present the salient histopathologic and molecular features of precursor lesions of pancreatic cancer as well as methods that have proved to be useful within experimental studies.

 

----------------------------------------------------

[252]

TÍTULO / TITLE:  - Significance of Notch1-signaling Pathway in Human Pancreatic Development and Carcinogenesis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Appl Immunohistochem Mol Morphol. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAI.0b013e3182655ab7

AUTORES / AUTHORS:  - Hu H; Zhou L; Awadallah A; Xin W

INSTITUCIÓN / INSTITUTION:  - *Department of Pathology, University Hospitals Case Medical Center daggerDepartment of Pathology, Case Western Reserve University, Cleveland, OH.

RESUMEN / SUMMARY:  - In animal studies, Notch1-signaling pathway plays an important role in the pancreatic embryogenesis by promoting pancreatic progenitor cells self-renewal and exocrine linage development. The persistent activation of Notch pathway could arrest the organ development and keep cells at an undifferentiated stage. Studies have shown that Notch1-signaling pathway is upregulated in invasive pancreatic ductal adenocarcinoma (PDAC). Here we examined the expression pattern of Notch1 and Hes1 in human fetal pancreatic tissues to elucidate the role of Notch1 in human pancreatic embryonic development. We also compared Notch1 expression in tissues from PDAC, chronic pancreatitis and pancreatic intraepithelial neoplasm.  Our data show that Notch1/Hes1-signaling pathway is activated during early pancreatic embryogenesis and reaches the highest at birth. After pancreas is fully developed, Notch1/Hes1 pathway is inactivated even though Notch1 protein cell-surface expression is upregulated. We also showed that the expression of both Notch1 and Hes1 are present in 50% (33/66) of PDACs, but not in pancreatic intraepithelial neoplasms. These findings indicate that Notch1 activation is only apparent in late stage of pancreatic carcinogenesis, suggesting that treatment with Notch-signaling inhibitors including gamma-secretase should be selectively used for PDACs with confirmed Notch1-signaling activation.

 

----------------------------------------------------

[253]

TÍTULO / TITLE:  - Lipoma of the pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreatology. 2012 Nov-Dec;12(6):493-4.

AUTORES / AUTHORS:  - Maderuelo MM; Gonzalez Valverde FM; Marin-Blazquez AA

INSTITUCIÓN / INSTITUTION:  - Surgery Department, Hospital General Universitario Reina Sofia de Murcia, Avda. Intendente Jorge Palacios n degrees 1, 30003 Murcia, España.

 

----------------------------------------------------

[254]

TÍTULO / TITLE:  - Celiac plexus block and neurolysis for pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Pain Headache Rep. 2013 Feb;17(2):310. doi: 10.1007/s11916-012-0310-y.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11916-012-0310-y

AUTORES / AUTHORS:  - Bahn BM; Erdek MA

INSTITUCIÓN / INSTITUTION:  - The Johns Hopkins University School of Medicine, Baltimore, MD, USA, Bahn@TPMclinic.com.

RESUMEN / SUMMARY:  - Neurolytic celiac plexus blocks (NCPB) have been performed for many years for the treatment of cancer and some non-cancer pain conditions associated with the upper gastrointestinal tract. The block can provide adequate pain relief from the area  of the distal esophagus to the transverse colon, and can be approached from a variety of ways. This is a review of the anatomy, patient selection, technique, medications used, possible complications, and efficacy of the treatment.

 

----------------------------------------------------

[255]

TÍTULO / TITLE:  - Considerations for sequencing analyses of pancreatic cancer progression and metastasis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:121-9. doi: 10.1007/978-1-62703-287-2_6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_6

AUTORES / AUTHORS:  - Makohon-Moore A; Iacobuzio-Donahue CA

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

RESUMEN / SUMMARY:  - Sequencing analyses have been invaluable in identifying the genes associated with pancreatic -carcinogenesis. However, whereas gene discovery related to carcinogenesis can be fairly straightforward, there are several additional aspects of experimental design that need to be considered when performing genetic analyses of metastatic disease. This chapter aims to review these issues and provide examples of the types of data generated.

 

----------------------------------------------------

[256]

TÍTULO / TITLE:  - MicroRNA-34b inhibits pancreatic cancer metastasis through repressing Smad3.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Mol Med. 2013 Jan 9.

AUTORES / AUTHORS:  - Liu C; Cheng H; Shi S; Cui X; Yang J; Chen L; Cai X; Lu Y; Wu C; Yao W; Qin Y; Liu L; Long J; Xu J; Li M; Yu X

INSTITUCIÓN / INSTITUTION:  - The Vivian L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, Texas 77030, USA. Min.Li@uth.tmc.edu.

RESUMEN / SUMMARY:  - Pancreatic cancer is characterized by extremely poor prognosis because of early recurrence and metastasis, and increasing evidence supports the critical role of  microRNA in cancer progression. Here we identified that microRNA-34b functioned as a tumor-suppressing microRNA by targeting oncogenic Smad3 in pancreatic cancer. As a hypovascular tumor with a potential endoplasmic reticulum stress microenvironment, miR-34b was silenced after ER stress inducer thapsigargin (Tg)  treatment and negatively regulated by ER stress chaperone glucose regulated protein 78 (GRP78) in pancreatic cancer cells. In human specimens, we found that  miR-34b was down-regulated in pancreatic cancer tissues and low level of miR-34b  expression was positively correlated with tumor-node-metastasis (TNM) stage, lymph-node metastasis and overall survival. Functional assays showed that over-expression of miR-34b inhibited pancreatic cancer progression in vitro and in vivo. In addition, Smad3 was demonstrated as a direct target of miR-34b and negatively regulated by miR-34b at mRNA and protein levels. Luciferase assays confirmed that miR-34b could directly bind to the 3’untranslated region of Smad3. An inverse correlation between miR-34b and Smad3 was observed in 64 pancreatic cancer tissues. Our findings indicate that miR-34b acts as a tumor metastasis suppressor through negatively modulating Smad3, which may provide a potential therapeutic strategy for pancreatic cancer.

 

----------------------------------------------------

[257]

TÍTULO / TITLE:  - Disputed paternity: the uncertain ancestry of pancreatic ductal neoplasia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Cell. 2012 Dec 11;22(6):701-3. doi: 10.1016/j.ccr.2012.11.015.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ccr.2012.11.015

AUTORES / AUTHORS:  - Maitra A; Leach SD

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA.

RESUMEN / SUMMARY:  - In this issue of Cancer Cell, Kopp and colleagues report that pancreatic ductal cells are largely refractory to the induction of pancreatic neoplasia. Whereas a  rare ductal subpopulation may still prove capable of neoplastic transformation, these findings refocus attention on acinar and other non-ductal cell types as initiators of this deadly neoplasm.

 

----------------------------------------------------

[258]

TÍTULO / TITLE:  - A Method for Conducting Highly Sensitive MicroRNA In Situ Hybridization and Immunohistochemical Analysis in Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:43-59. doi: 10.1007/978-1-62703-287-2_4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_4

AUTORES / AUTHORS:  - Sempere LF; Korc M

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Dartmouth Hitchcock Medical Center, Hanover, NH, USA.

RESUMEN / SUMMARY:  - Profiling experiments in whole tissue biopsies have linked altered expression of  microRNAs (miRNAs) to different types of cancer, including pancreatic ductal adenocarcinoma (PDAC). Emerging evidence indicates that altered miRNA expression  can occur in different cellular compartments (cancer and non-cancer cells) in tumor lesions, and thus it is important to ascertain which specific cell type expresses a particulars miRNA in PDAC tissues. Here, we describe a highly sensitive fluorescence-based ISH method to visualize miRNA accumulation within individual cells in formalin-fixed paraffin-embedded (FFPE) tissue sections using 5’ and 3’ terminally fluorescein-labeled locked nucleic acid (LNA)-modified probes. We describe a multicolor ISH/IHC method based on sequential rounds of horseradish peroxidase (HRP)-mediated tyramide signal amplification (TSA) reactions with different in-house synthesized fluorochrome-conjugated substrates  that enable co-detection of miRNAs, abundant noncoding RNAs and protein markers for signal quantification, and cell type co-localization studies in FFPE pancreatic tissue sections from clinical specimens and mouse models of PDAC.

 

----------------------------------------------------

[259]

TÍTULO / TITLE:  - Tumor-stromal interactions in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Crit Rev Oncog. 2013;18(1-2):135-51.

AUTORES / AUTHORS:  - Whatcott C; Han H; Posner RG; Von Hoff DD

INSTITUCIÓN / INSTITUTION:  - Clinical Translational Research Division, The Translational Genomics Research Institute (TGEN), Phoenix, Arizona.

RESUMEN / SUMMARY:  - The tumor associated stroma has been described in recent years as being complicit in tumor growth in pancreatic cancer. The stroma hosts a variety of components of both cellular and molecular makeup. In normal tissues, the stroma provides nutrients and regulatory signals for proper cellular polarity and function. However, following oncogenic transformation, the stromal compartment is conscripted to provide stimulatory signals and protection to tumor cells. It is these tumor-stromal interactions that are currently of great therapeutic interest. Several key reports have suggested that therapeutic targeting of the tumor-stromal interactions in pancreatic cancer has the potential to offer survival benefit. In this review, we will discuss the tumor-stromal interactions  that contribute to tumor growth and progression, and ways in which we might counter these interactions.

 

----------------------------------------------------

[260]

TÍTULO / TITLE:  - The Role of the FOLFIRINOX Regimen for Advanced Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Oncol Rep. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11912-012-0290-4

AUTORES / AUTHORS:  - Conroy T; Gavoille C; Samalin E; Ychou M; Ducreux M

INSTITUCIÓN / INSTITUTION:  - EA 4360 and Department of Medical Oncology, Centre Alexis Vautrin, Universite de  Lorraine, CS 30519, 54519, Vandoeuvre-les-Nancy Cedex, France, t.conroy@nancy.unicancer.fr.

RESUMEN / SUMMARY:  - In 2010, the FOLFIRINOX regimen (bolus and infusional 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) emerged as a new option in patients with metastatic  pancreatic cancer and a good performance status. However, at that time, some doubts were raised regarding safety issues. Similarly, no data on FOLFIRINOX were published in patients with unresectable/locally advanced or borderline resectable pancreatic cancer. This article presents the available experience with FOLFIRINOX outside clinical trials in metastatic and locally advanced pancreatic cancer patients. The safety of the regimen in patients with biliary stents and in previously treated patients is also described. FOLFIRINOX usage in clinical practice, including modification of the regimen (omission of bolus 5-fluorouracil; FOLFOXIRI regimen), is also presented. These data suggest that a  phase III randomized study is warranted to further explore the role of FOLFIRINOX in locally advanced pancreatic cancer.

 

----------------------------------------------------

[261]

TÍTULO / TITLE:  - Cystic Neoplasms of the Pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Surg. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11605-012-2072-6

AUTORES / AUTHORS:  - Lennon AM; Wolfgang C

INSTITUCIÓN / INSTITUTION:  - The Johns Hopkins Hospital, Baltimore, MD, USA, amlennon@jhmi.edu.

RESUMEN / SUMMARY:  - Pancreatic cysts are being identified with increasing frequency due to a combination of increased awareness and more frequent use of cross sectional imaging. Cystic neoplasms of the pancreas range from completely benign to frankly malignant. Identifying pre-malignant cysts offers the opportunity to prevent the  development of pancreatic cancer. This article reviews the presentation, workup,  and non-operative and operative management of premalignant and malignant pancreatic cysts.

 

----------------------------------------------------

[262]

TÍTULO / TITLE:  - Immunohistochemistry of pancreatic neoplasia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;980:29-42. doi: 10.1007/978-1-62703-287-2_3.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-287-2_3

AUTORES / AUTHORS:  - Kaur S; Shimizu T; Baine MJ; Kumar S; Batra SK

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry and Molecular Biology, University of Nebraska Medical  Center, Omaha, NE, USA.

RESUMEN / SUMMARY:  - Immunohistochemistry (IHC) is a valuable tool to visualize the distribution and localization of specific cellular components within morphologically preserved tissue sections or cell preparations. It combines the histologic morphology of tissues for detecting the actual antigen distribution, specificity of antibody-antigen interaction for optimal detection, and sensitivity of immunochemical methods for assessing the amount of antigen in tissues. It is routinely used clinically to diagnose type (benign or malignant), stage, and grade of cancer using specific tumor markers. The application of IHC ranges from  disease diagnosis and prognosis to drug development and analysis of the pathobiological roles of various molecular players during disease development. Due to better availability of highly specific antibodies and optimal methodologies for performing immunohistochemical studies, IHC is being used at an expanding rate to understand pancreatic tumor biology as well as to study the fate of various molecular markers during the initiation, progression, and metastasis of pancreatic neoplasia. Herein, we describe the detailed protocol for IHC analyses of pancreatic intraepithelial neoplasia in tissues and fine needle aspirates from both human and mouse samples.

 

----------------------------------------------------

[263]

TÍTULO / TITLE:  - Acute pancreatitis: the onset digestive manifestation, in a patient with adult T-cell leukemia/lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Rom J Morphol Embryol. 2012;53(3 Suppl):847-50.

AUTORES / AUTHORS:  - Popescu M; Popov V; Popescu G; Dobrea C; Sandu A; Grigorean VT; Strambu V; Plesea IE

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Emergency County Hospital, Pitesti, Romania.

RESUMEN / SUMMARY:  - Acute pancreatitis is a common complication, which occurs with patients suffering from vesicular biliary lithiasis or chronic alcoholism. Hypercalcemia may determine acute pancreatitis, its causes being multiple: primary or secondary hyperparathyroidism, metabolic diseases of the bone, metastatic bone neoplasm, as well as lymphoproliferative syndromes caused by the HTLV-1 virus-adult T-cell leukemia/lymphoma (ATLL). ATLL is a malignant and aggressive lymphoproliferation  with the T-cell, associated with the infection caused by the HTLV-1 retrovirus. Organomegaly, cutaneous conditions, and hypercalcemia represent the main characteristics of the disease. From a hematologic point of view, we can notice the atypical lymphocytes (also known as flower cells, due to the shape of their nucleus), with a distinct CD4+ CD25+ phenotype. There have been reported few cases of patients who showed acute pancreatitis in the onset of the disease. We will describe the case of a patient whose diagnosis has not been an easy one, as  it showed multiple complications from a very early stage. CONCLUSIONS: The atypical onset of ATLL with acute pancreatitis is rarely reported. Its etiology seems to be hypercalcemia but pancreatic infiltration with ATLL cells cannot be ruled out. An attentive investigation of the peripheral blood sample and flow-cytometric tests of peripheral and medullar blood smear are very important for diagnosis. The patient showed from the very beginning severe neurological manifestations which developed to a coma. Causes could have been metabolic as well as CNS infiltration (as shown by the CT examination).

 

----------------------------------------------------

[264]

TÍTULO / TITLE:  - Clinicopathological features of 30 autopsy cases of pancreatic carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Nippon Med Sch. 2012;79(6):459-67.

AUTORES / AUTHORS:  - Matsuda Y; Hagio M; Naito Z; Ishiwata T

INSTITUCIÓN / INSTITUTION:  - Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School.

RESUMEN / SUMMARY:  - The annual incidence of pancreatic carcinoma has been increasing worldwide, and the overall 5-year survival rate has remained at approximately 5%. We re-evaluated 30 autopsy cases histologically diagnosed as pancreatic carcinoma from 1994 through 2010 at Nippon Medical School Hospital. The mean patient age was 69.5 years, with no significant differences between male and female patients. The location of the primary tumor was most often the head of the pancreas (46.7%), followed by the body (36.7%) and tail (16.7%). All patients had advanced-stage pancreatic carcinoma at diagnosis, which limited the therapeutic options. Surgical resection, radiation, and surgical resection with chemotherapy  were each performed for a single patient, and chemotherapy was performed for 5 patients. The other patients received only symptomatic therapy. The mean survival time from the first medical examination to death was short (5.5 months; range, 1-40 months). The cases were classified into 28 ductal adenocarcinomas, 1 acinar  cell carcinoma, and 1 intraductal papillary mucinous neoplasm (IPMN) with an associated invasive carcinoma. Death in most cases was directly related to the pancreatic carcinoma, including cachexia, carcinomatous peritonitis and pleuritis, hepatic failure and ileus due to metastasis, and malignancy-related disorders, such as coagulation disorders and immunodeficiency. The most frequent  site of metastasis was the lymph nodes, followed by the liver, peritoneum, spleen, lung and/or pleura, small intestine, adrenal gland, kidney, omentum, diaphragm, and bone. We classified the autopsy cases as showing distant metastasis or local infiltration. All cases with local infiltration were located  in the pancreatic head, but no difference was seen in other clinicopathological features between cases with local infiltration and cases with distant metastasis. Thus, the autopsies revealed an extremely poor prognosis for pancreatic carcinoma due to the tumor itself and malignancy-related disorders. The progression pattern (i.e., local infiltration or distant metastasis) may correlate with the location  of the primary tumor.

 

----------------------------------------------------

[265]

TÍTULO / TITLE:  - Ultra-high-resolution Images of Nestin and Vimentin in Pancreatic Carcinoma Cells Using 2 Novel Microscopy Systems.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Nippon Med Sch. 2012;79(6):392-3.

AUTORES / AUTHORS:  - Yoshimura H; Matsuda Y; Naito Z; Murase M; Kawamoto Y; Ishiwata T

INSTITUCIÓN / INSTITUTION:  - Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School.

 

----------------------------------------------------

[266]

TÍTULO / TITLE:  - High-intensity focused ultrasound treatment for patients with unresectable pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hepatobiliary Pancreat Dis Int. 2012 Dec 15;11(6):655-60.

AUTORES / AUTHORS:  - Li PZ; Zhu SH; He W; Zhu LY; Liu SP; Liu Y; Wang GH; Ye F

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, Third Xiangya Hospital, Central South University,  Changsha 410013, China.

RESUMEN / SUMMARY:  - BACKGROUND: High-intensity focused ultrasound (HIFU) is a non-invasive method of  solid tissue ablation therapy. However, only a few studies have reported the effect of HIFU for unresectable pancreatic cancer. This study aimed to evaluate the clinical benefits, survival time and complications associated with the use of HIFU ablation in patients with unresectable pancreatic cancer. METHODS: Twenty-five patients with unresectable pancreatic cancer were enrolled in our study. All patients received HIFU therapy for tumors at least once. The therapeutic effects of HIFU was evaluated in terms of Karnofsky performance status (KPS) scores, pain relief, serum CA19-9, and imaging by B-US and CT before and after the therapy. We also recorded median overall survival time and complications caused by the treatment. RESULTS: In the 25 patients, KPS scores were above 60, and increased KPS was observed in 23 patients after treatment. Pain relief occurred in 23 patients. Serum CA19-9 levels were significantly reduced one month after HIFU treatment and became negative in 5 patients. B-US revealed enhanced tumor echogenicity in 13 patients and decreased tumor blood supply in 9. Tumor necrosis was confirmed by CT in 8 patients one month after HIFU treatment. The median overall survival time was 10 months, and the 1-year survival rate was 42%. No severe complications were observed after HIFU treatment. CONCLUSION: HIFU can effectively relieve pain, increase KPS, decrease  tumor growth and prolong the survival time of patients with unresectable pancreatic cancer.

 

----------------------------------------------------

[267]

TÍTULO / TITLE:  - New developments in pancreatic cancer treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Minerva Gastroenterol Dietol. 2012 Dec;58(4):427-43.

AUTORES / AUTHORS:  - Krug S; Michl P

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Endocrinology and Metabolism, Philipps University Marburg, Marburg, Germany - michlp@med.uni-marburg.de.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinomas belong to the most aggressive solid malignancies. The devastating prognosis of this tumor entity is associated with a high degree of resistance to systemic therapy approaches. Although new combination chemotherapy regimens have recently demonstrated a significant survival benefit compared to gemcitabine-based therapies, the search for novel treatment options still remains a huge challenge. After numerous potential targets have proven to be futile in clinical trials, recent efforts have been made to both improve drug delivery and to identify drugs targeting novel signalling pathways within the tumors including the putative stem cell compartment and the tumor stroma. Furthermore, predictive markers are needed to define tailored treatment regimens according to the molecular profile of individual tumors. In this review, current therapeutic strategies as well as emerging avenues for systemic therapy and response prediction for individualized  therapy of pancreatic cancer patients are discussed which are currently evaluated to overcome the highly drug-resistant phenotype of this malignancy.

 

----------------------------------------------------

[268]

TÍTULO / TITLE:  - Oral agents for treatment of patients with advanced pancreatic neuroendocrine tumors: could pharmaeconomic, cost-effectiveness data play a significant role?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JOP. 2013 Jan 10;14(1):102-4. doi: 10.6092/1590-8577/1354.

AUTORES / AUTHORS:  - Barna ME; Uomo I; Pastorello M

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacy, Local Health Unit. Palermo, Italy. ilariauomo@libero.it.

----------------------------------------------------

[269]

TÍTULO / TITLE:  - K-RAS mutation analysis in a case of pancreatic cystic tumour: an additional tool in making decision of surgical management.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Minerva Chir. 2012 Oct;67(5):464-6.

AUTORES / AUTHORS:  - Boldorini R; Garavoglia M; Gentili S; Oldani A; Portigliotti L

INSTITUCIÓN / INSTITUTION:  - Department of Medical Sciences, Faculty of Medicine, University of the Eastern Piedmont Amedeo Avogadro, Novara, Italy - alberto.oldani@libero.it.

 

----------------------------------------------------

[270]

TÍTULO / TITLE:  - Self-expanding metal stents (SEMS) provide superior outcomes compared to plastic  stents for pancreatic cancer patients undergoing neoadjuvant therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Oncol. 2012 Dec;3(4):309-13. doi: 10.3978/j.issn.2078-6891.2011.050.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2078-6891.2011.050

AUTORES / AUTHORS:  - Adams MA; Anderson MA; Myles JD; Khalatbari S; Scheiman JM

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System;

RESUMEN / SUMMARY:  - BACKGROUND: Neoadjuvant therapy is increasingly utilized for pancreatic cancer patients to decrease tumor burden in anticipation of later surgical resection. However, infectious complications such as life threatening cholangitis may occur  for those with biliary obstruction. We hypothesized that placement of metal rather than plastic stents in such patients results in lower rates of stent-related complications, leading to improved clinical outcomes. METHODS: Retrospective cohort of pancreatic cancer patients treated by the University of Michigan Multidisciplinary Pancreatic Cancer Destination Program between January  2005 and June 2010. Only patients undergoing neoadjuvant therapy with one or more biliary stents placed for malignant obstruction were studied. Time to stent complication was compared between metal and plastic stents. The complication rate was estimated as the ratio of complications to total stent exposure time and 95%  confidence intervals were calculated. RESULTS: 52 patients met inclusion criteria. A total of 113 stents were placed in 52 patients (70 plastic, 43 metal). The complication rate was almost 7 times higher with plastic stents, 0.20 (95% CI, 0.14-0.30), than with metal stents, 0.03 (95% CI, 0.01-0.06). Moreover,  the rate of hospitalization for stent-related complications was 3-fold higher in  the plastic stent group than the metal stent group. The first quartile estimate of time to stent complication was almost 5 times longer for metal than for plastic stents (44 vs. 200 days) (P<0.0001). CONCLUSION: Compelling evidence indicates that self-expanding metal, not plastic stents should be used for malignant biliary obstruction in patients undergoing neoadjuvant therapy for pancreatic cancer.

----------------------------------------------------

[271]

TÍTULO / TITLE:  - Extensive propagation of a pancreatic pseudocyst along the lower limb through the sciatic foramen.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JBR-BTR. 2012 Sep-Oct;95(5):289-93.

AUTORES / AUTHORS:  - Coulier B; Maldague P; Bueres-Dominguez I; Ramboux A; Pierard F; Bienfait B

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Radiology, Clinique St Luc, Bouge, Namur, Belgium. bcoulier@skynet.be

RESUMEN / SUMMARY:  - The extremely rare extensive propagation of a giant retroperitoneal pancreatic pseudocyst into the posterior compartment of the lower limb as far as the knee is reported. The extension was found producing through the sciatic foramen and the full diagnosis was made by MDCT. A complete healing was progressively obtained in the 78-year old female after a six months period of sequential multidisciplinary  therapeutic approach comprising combined medical and surgical intra-abdominal and external drainage.

 

----------------------------------------------------

[272]

TÍTULO / TITLE:  - Is determination of matrix metalloproteinases and their tissue inhibitors serum concentrations useful in patients with gastroenteropancreatic and bronchopulmonary neuroendocrine neoplasms?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endokrynol Pol. 2012;63(6):470-6.

AUTORES / AUTHORS:  - Blicharz-Dorniak J; Kos-Kudla B; Foltyn W; Kajdaniuk D; Marek B; Zemczak A; Strzelczyk J

RESUMEN / SUMMARY:  - Introduction: Gastroenteropancreatic (GEP) and bronchopulmonary (BP) neurendocrine neoplasms (NENs) are rare and slowly growing tumours. Matrix metalloproteinases (MMPs) degrade extracellular matrix and are responsible for invasion and metastasis. Tissue inhibitors of matrix metalloproteinases (TIMPs) affect the invasiveness of tumour cells and the formation of distant metastases.  The aim of this study was to evaluate selected MMPs (MMP2 and MMP9) and their tissue inhibitors (TIMP1 and TIMP2) depending on the pTNM classification, grading, and the occurrence of metastases. Material and methods: The study group  consisted of 86 patients with GEP NENs. The control group consisted of 31 healthy volunteers. Serum levels of TIMP1, TIMP2, MMP2 and MMP9 were determined by ELISA  (R&D Systems) in all the study subjects. The statistical calculations were performed using MedCalc. Results: We observed significant differences in MMP2 and TIMP1 levels between the study group with NENs and the control group. TIMP1 levels were significantly higher in patients with high-grade NEN (NEC, neuroendocrine carcinoma) compared to patients with low-grade tumour (NET G1, neuroendocrine tumours G1) (p < 0.017). We also observed a significant correlation between TIMP1 levels and the presence of metastases in the group of patients with GEP NENs, and also higher TIMP1 levels than those in the patients without metastases (p < 0.05). We also found a higher likelihood of metastases in patients with GEP NENs with TIMP1 levels exceeding 206.4 ng/mL. Conclusions: Patients with NENs secreted larger quantities of MMP2 and TIMP1. TIMP1 may be considered a marker of metastases in patients with GEP NENs. (Endokrynol Pol 2012; 63 (6): 470-476).

 

----------------------------------------------------

[273]

TÍTULO / TITLE:  - Self-expanding metal stents for preoperative biliary drainage in patients receiving neoadjuvant therapy for pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Oncol. 2012 Dec;3(4):304-5. doi: 10.3978/j.issn.2078-6891.2012.048.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2078-6891.2012.048

AUTORES / AUTHORS:  - Singh A; Lee JH

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Hepatology, and Nutrition, M D Anderson Cancer Center, Houston, Texas, USA.

----------------------------------------------------

[274]

TÍTULO / TITLE:  - The actual management of early pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Minerva Gastroenterol Dietol. 2012 Dec;58(4):321-30.

AUTORES / AUTHORS:  - Iglesias Garcia J; Larino-Noia J; Dominguez-Munoz JE

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology and Foundation for Research in Digestive Diseases  (FIENAD) University Hospital, Santiago de Compostela, España - julio.iglesias.garcia@sergas.es.

RESUMEN / SUMMARY:  - Pancreatic cancer (PC) is a highly lethal disease. Early diagnosis remains the only possibility nowadays for an intention to cure the disease, since prognosis of PC is significantly better in patients diagnosed of small (<2 cm), well differentiated, stages I and II pancreatic tumors. However, the best approach would be to detect precursor lesions, like Intraductal papillary mucinous neoplasm (IPMN) or PanIN lesions. In this setting the best technique to diagnose  either small PC and/or IPMN and PanIN lesions is clearly endoscopic ultrasound. However, detection of these lesions is very difficult, hampered by the absence of clinical manifestations of PC at these early stages. The implementation of screening programs, which - given the incidence of PC - is not cost effective for the general population, in high-risk individuals, may lead to increase the detection of PC an early stages as well as precursor lesion. When focusing on treatment, PC patients are best cared by multidisciplinary teams. For patients with resectable disease surgery remains the treatment of choice, followed by postoperative treatment. When precursor lesions are detected, mainly IPMN, treatment should be individualized, following latest international guidelines.

 

----------------------------------------------------

[275]

TÍTULO / TITLE:  - Discovering the route from inflammation to pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Minerva Gastroenterol Dietol. 2012 Dec;58(4):283-97.

AUTORES / AUTHORS:  - Momi N; Kaur S; Krishn SR; Batra SK

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry and Molecular Biology, University of Nebraska Medical  Center, Omaha, NE, USA - sbatra@unmc.edu.

RESUMEN / SUMMARY:  - Pancreatic cancer (PC) remains a complex malignancy with the worst prognosis, lack of early diagnostic symptoms and resistance to conventional chemo- and radiotherapies. A better understanding of the etiology and early developmental events of PC requires profound attention. The evolution of fully blown PC from initial pancreatic injury is a multi-factorial phenomenon with a series of sequential events. The initial acute infection or tissue damage triggers inflammation that, in conjunction with innate immunity, establishes a state of homeostasis to limit harm to the body. Recurrent pancreatic injuries due to genetic susceptibility, smoking, unhealthy diet, and alcohol abuse induces a pro-inflammatory milieu, consisting of various types of immune cells, cytokines,  chemokines, growth factors and restructured extracellular matrix, leading to prolonged inflammatory/chronic conditions. Cells having sustained DNA damage and/or mutagenic assault take advantage of this prolonged inflammatory response and aid in the initiation and development of neoplastic/fibrotic events. Eventually, many tumor-stromal interactions result in a chaotic environment accompanied by a loss of immune surveillance and repair response, thereby leading to PC. A better understanding of the inflammatory markers defining this “injury-inflammation-cancer” pathway would help to identify novel molecular targets for early screening and therapeutic intervention for this lethal malignancy.

 

----------------------------------------------------

[276]

TÍTULO / TITLE:  - Pancreatic neuroendocrine neoplasms.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Minerva Gastroenterol Dietol. 2012 Dec;58(4):401-26.

AUTORES / AUTHORS:  - Horsch D; Bert T; Schrader J; Hommann M; Kaem-Merer D; Petrovitch A; Zaknun J; Baum RP

INSTITUCIÓN / INSTITUTION:  - Center for Neuroendocrine Tumors Bad Berka ENETS Center of excellence, Bad Berka, Germany - dieter.hoersch@zentralklinik.de.

RESUMEN / SUMMARY:  - Pancreatic neuroendocrine tumors originate from the diffuse neuroendocrine system in the pancreatic region. These tumors exhibit a rising incidence despite their rareness and due to their benign behavior a considerable prevalence. Pathogenesis of pancreatic neuroendocrine tumors is characterized by common pathways of hereditary and sporadic tumors. Pancreatic neuroendocrine tumors may secrete peptide hormones or biogenic amines in an autonomous fashion as functional active tumors. Pathological grading and staging by TNM systems has been established in recent years classifying well and moderately differentiated pancreatice neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Chromogranin A and less so pancreatic polypeptide are suitable tumor markers for  pancreatic neuroendocrine tumors. Expression of receptors for somatostatin is the basis of treatment of pancreatic neuroendocrine tumors with somatostatin analogues as antisecretive and antiproliferative agents. In addition, somatostatin scintigraphy or PET/CT allows comprehensive diagnosis of pancreatic  neuroendocrine tumors, which should be supported by (endoscopic and contrast enhanced) ultrasound, CT and MRI. Therapy of pancreatic neuroendocrine tumors consists of somatostatin analogues, chemotherapy, targeted therapy and peptide receptor radionuclide therapy. Two molecular substances hav been registered for pancreatic neuroendocrine tumors recently, sunitinib (Sutent®) and everolimus (Afinitor®). Predominant tumor load in the liver may be treated by local ablative therapy or liver transplantation. These treatment options have been included in guidelines of several professional societies and weighted for sequential therapy of patients with pancreatic neuroendocrine tumors according to effects and side effects.

 

----------------------------------------------------

[277]

TÍTULO / TITLE:  - Diabetes and pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Minerva Gastroenterol Dietol. 2012 Dec;58(4):331-46.

AUTORES / AUTHORS:  - Muniraj T; Chari ST

INSTITUCIÓN / INSTITUTION:  - Yale University School of Medicine, New Haven, CT USA - chari.suresh@mayo.edu.

RESUMEN / SUMMARY:  - The relationship between diabetes and pancreatic cancer is complex. Diabetes or impaired glucose tolerance is present in more than 2/3rd of pancreatic cancer patients. Epidemiological studies have consistently shown a modest increase in the risk of pancreatic cancer in type 2 diabetes, with an inverse relationship to duration of disease. Additionally, recent studies suggest that anti-diabetic medications may modulate the risk of pancreatic cancer in type 2 diabetes. Subjects >50 years of age with new onset diabetes are at higher risk of having pancreatic cancer. However, to screen new-onset diabetes for pancreatic cancer, additional markers are needed that can distinguish pancreatic cancer-associated diabetes from type 2 diabetes.

 

----------------------------------------------------

[278]

TÍTULO / TITLE:  - Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2012;2:209. doi: 10.3389/fonc.2012.00209. Epub 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2012.00209

AUTORES / AUTHORS:  - Karamitopoulou E

INSTITUCIÓN / INSTITUTION:  - Clinical Pathology Division, Institute of Pathology, University of Bern Bern, Switzerland.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a  5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and  resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and  to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

----------------------------------------------------

[279]

TÍTULO / TITLE:  - Increased plasma microRNA and CD133/CK18-positive cancer cells in the pleural fluid of a pancreatic cancer patient with liver and pleural metastases and correlation with chemoresistance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Oct;4(4):691-694. Epub 2012 Jul 13.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.798

AUTORES / AUTHORS:  - Ren C; Chen H; Han C; Wang D; Fu D

INSTITUCIÓN / INSTITUTION:  - Medical Laboratory;

RESUMEN / SUMMARY:  - We report a case of notably increased plasma levels of microRNA (miR)-21, miR-25, miR-103 and miR-151 in a pancreatic cancer patient with liver and pleural metastases. CD45-coated immunomagnetic beads detected an enrichment of malignant  cancer cells in the pleural fluid, and CD133(+)CK18(+) cancer cells were identified. Using computer tomography (CT) combined with cancer cells stained in  the pleural fluid, a previously healthy 60-year-old male was diagnosed with pancreatic cancer with multiple liver tumor metastases. Cancer antigen 19-9 (CA19-9), alkaline phosphatase (ALP) and gamma-glutamate-transpeptidase (gamma-GT) were notably increased in the serum, and carcinoembryonic antigen (CEA) was increased in the pleural fluid. The patient succumbed to the disease three months following standard chemotherapy. The increased levels of plasma miR-21, miR-25, miR-103 and miR-151, as well as the identification of CD133(+)CK18(+) cells in the pleural fluid of a pancreatic cancer patient with liver metastases, may regulate the molecular mechanisms involved in chemoresistance. The patient was insensitive to chemotherapy and succumbed 3 months later. Full elucidation of the molecular and pathological features of pancreatic cancer may be a novel strategy for diagnosis and tailored therapy.

----------------------------------------------------

[280]

TÍTULO / TITLE:  - Quantitative low mechanical index contrast-enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Gastroenterol. 2013 Jan 3;13(1):2. doi: 10.1186/1471-230X-13-2.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-230X-13-2

AUTORES / AUTHORS:  - Gheonea DI; Streba CT; Ciurea T; Saftoiu A

INSTITUCIÓN / INSTITUTION:  - Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy, Craiova, 200349, Romania. costinstreba@gmail.com.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Second-generation intravenous blood-pool ultrasound contrast agents are increasingly used in endoscopic ultrasound (EUS) for characterization of microvascularization, differential diagnosis of benign and malignant focal lesions, as well as improved staging and guidance of therapeutic  procedures. METHODS: The aim of our study was to prospectively compare the vascularisation patterns in chronic pseudotumoral pancreatitis and pancreatic cancer using quantitative low mechanical index (MI) contrast-enhanced EUS. We included 51 patients with chronic pseudotumoral pancreatitis (n = 19) and pancreatic cancer (n = 32). Perfusion imaging started with a bolus injection of Sonovue (2.4 ml), followed by analysis in the early arterial (wash-in) and late venous (wash-out) phase. Perfusion analysis was performed by post-processing of the raw data (time intensity curve [TIC] analysis). TIC analysis was performed inside the tumor and the pancreatic parenchyma, with depiction of the dynamic vascular pattern generated by specific software. Statistical analysis was performed on raw data extracted from the TIC analysis. Final diagnosis was based  on a combination of EUS-FNA, surgery and follow-up of minimum 6 months in negative cases. RESULTS: The sensitivity and specificity of low MI contrast enhanced EUS using TIC were sensitivity and specificity of low MI contrast enhanced EUS using TIC analysis were 93.75% (95% CI = 77.77 - 98.91%) and 89.47%  (95% CI = 65.46 - 98.15%), respectively. Pseudotumoral chronic pancreatitis showed in the majority of cases a hypervascular appearance in the early arterial  phase of contrast-enhancement, with a dynamic enhancement pattern similar with the rest of the parenchyma. Statistical analysis of the resulting series of individual intensities revealed no statistically relevant differences (p = .78).  Pancreatic adenocarcinoma was usually a hypovascular lesion, showing low contrast-enhancement during the early arterial and also during the late venous phase of contrast-enhancement, also lower than the normal surrounding parenchyma. We found statistically significant differences in values during TIC analysis (p < .001). CONCLUSIONS: Low MI contrast enhanced EUS technique is expected to improve the differential diagnosis of focal pancreatic lesions. However, further multicentric randomized studies will confirm the exact role of the technique and  its place in imaging assessment of focal pancreatic lesions.

 

----------------------------------------------------

[281]

TÍTULO / TITLE:  - WNT5A-NFAT Signaling Mediates Resistance to Apoptosis in Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neoplasia. 2013 Jan;15(1):11-22.

AUTORES / AUTHORS:  - Griesmann H; Ripka S; Pralle M; Ellenrieder V; Baumgart S; Buchholz M; Pilarsky C; Aust D; Gress TM; Michl P

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology and Endocrinology, University Hospital, Philipps-University, Marburg, Germany.

RESUMEN / SUMMARY:  - INTRODUCTION: WNT5A belongs to the Wnt family of secreted signaling molecules. Using transcriptional profiling, we previously identified WNT5A as target of the  antiapoptotic transcription factor CUX1 and demonstrated high expression levels in pancreatic cancer. However, the impact of WNT5A on drug resistance and the signaling pathways employed by WNT5A remain to be elucidated. OBJECTIVES: This project aims to decipher the impact of WNT5A on resistance to apoptosis and the signaling pathways employed by WNT5A in pancreatic cancer. METHODS: The impact of WNT5A and its downstream effectors on tumor growth and drug resistance was studied in vitro and in xenograft models in vivo. Tissue microarrays of pancreatic cancer specimens were employed for immunohistochemical studies. RESULTS: Knockdown of WNT5A results in a significant increase in drug-induced apoptosis. In contrast, overexpression of WNT5A or addition of recombinant WNT5A  mediates resistance to apoptosis in vitro. In our attempt to identify downstream  effectors of WNT5A, we identified the transcription factor nuclear factor of activated T cells c2 (NFATc2) as transcriptional target of WNT5A signaling. NFATc2 confers a strong antiapoptotic phenotype mediating at least in part the effects of WNT5A on drug resistance and tumor cell survival. In vivo, WNT5A expression leads to resistance to gemcitabine-induced apoptosis in a xenograft model, which is paralleled by up-regulation of NFATc2. Both WNT5A and NFATc2 proteins are highly expressed in human pancreatic cancer tissues and their expression levels correlated significantly. CONCLUSION: We identified the WNT5A-NFATc2 axis as important mediator of drug resistance in pancreatic cancer.

 

----------------------------------------------------

[282]

TÍTULO / TITLE:  - Endogenous n-3 Polyunsaturated Fatty Acids Delay Progression of Pancreatic Ductal Adenocarcinoma in Fat-1-p48(Cre/+)-LSL-Kras(G12D/+) Mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neoplasia. 2012 Dec;14(12):1249-59.

AUTORES / AUTHORS:  - Mohammed A; Janakiram NB; Brewer M; Duff A; Lightfoot S; Brush RS; Anderson RE; Rao CV

INSTITUCIÓN / INSTITUTION:  - Center for Cancer Prevention and Drug Development, Department of Medicine, Hematology/Oncology Section, Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK.

RESUMEN / SUMMARY:  - Preclinical studies suggest that diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for prevention of pancreatic cancer. Nutritional intervention studies are often complex, and there is no clear evidence, without potential confounding factors, on whether conversion of n-6 PUFAs to n-3 PUFAs in pancreatic tissues would provide protection. Experiments were designed using n-3 fatty acid desaturase (Fat-1) transgenic mice, which can  convert n-6 PUFA to n-3 FAs endogenously, to determine the impact of n-3 PUFAs on pancreatic intraepithelial neoplasms (PanINs) and their progression to pancreatic ductal adenocarcinoma (PDAC). Six-weekold female p48(Cre/+)-LSL-Kras(G12D/+) andcompoundFat-1-p48(Cre/+)-LSL-Kras(G12D/+) mice were fed (AIN-76A) diets containing 10% safflower oil for 35 weeks. Pancreata were evaluated histopathologically for PanINs and PDAC. Results showed a dramatic reduction in incidence of PDAC (84%; P < .02) in Fat-1-p48(Cre/+)-LSL-Kras(G12D/+) mice compared to p48(Cre/+)-LSL-Kras(G12D/+) mice. Importantly, significant reductions of pancreatic ducts with carcinoma (90%; P < .0001) and PanIN 3 ( approximately 50%; P < .001) lesions were observed in the compound transgenic mice. The levels  of n-3 PUFA were much higher (>85%; P < .05-0.01) in pancreas of compound transgenic mice than in those of p48(Cre/+)-LSL-Kras(G12D/+) mice. Molecular analysis of the pancreas showed a significant down-regulation of proliferating cell nuclear antigen, cyclooxygenase-2, 5-lipoxygenase (5-LOX), 5-LOX-activating  protein, Bcl-2, and cyclin D1 expression levels in Fat-1-p48(Cre/+)-LSL-Kras(G12D/+) mice compared to p48(Cre/+)-LSL-Kras(G12D/+) mice. These data highlight the promise of dietary n-3 FAs for chemoprevention of  pancreatic cancer in high-risk individuals.

 

----------------------------------------------------

[283]

TÍTULO / TITLE:  - Nicotine Induces Inhibitor of Differentiation-1 in a Src-dependent Pathway Promoting Metastasis and Chemoresistance in Pancreatic Adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neoplasia. 2012 Dec;14(12):1102-14.

AUTORES / AUTHORS:  - Trevino JG; Pillai S; Kunigal S; Singh S; Fulp WJ; Centeno BA; Chellappan SP

INSTITUCIÓN / INSTITUTION:  - Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

RESUMEN / SUMMARY:  - Smoking is a significant risk factor for pancreatic cancer, but the molecular mechanisms by which tobacco smoke components promote the growth and progression of these cancers are not fully understood. While nicotine, the addictive component of tobacco smoke, is not a carcinogen, it has been shown to promote the growth of non-small cell lung and pancreatic cancers in a receptor-dependent fashion. Here, we show that stimulation of pancreatic cancer cells with nicotine  concentrations that are within the range of human exposure results in activation  of Src kinase, which facilitated the induction of the inhibitor of differentiation-1 (Id1) transcription factor. Depletion of Id1 prevented nicotine-mediated induction of proliferation and invasion of pancreatic cancer cells, indicating that it is a major mediator of nicotine function. Nicotine could promote the growth and metastasis of pancreatic cancers orthotopically implanted into SCID mice; in addition, cells stably expressing a short hairpin RNA for Id1 did not grow or metastasize in response to nicotine. Nicotine could also confer resistance to apoptosis induced by gemcitabine in pancreatic cancer cells in vitro and depletion of Src or Id1 rendered the cells sensitive to gemcitabine. Further, nicotine could effectively inhibit the chemotherapeutic effects of gemcitabine on pancreatic tumors xenografted into mice. Clinical analyses of resected pancreatic cancer specimens demonstrated a statistically significant correlation between Id1 expression and phospho-Src, tumor grade/differentiation, and worsening overall patient survival. These results demonstrate that exposure to tobacco smoke components might promote pancreatic cancer progression, metastasis, and chemoresistance and highlight the role of Id1 in these processes.

 

----------------------------------------------------

[284]

TÍTULO / TITLE:  - Gamma-amino Butyric Acid (GABA) Prevents the Induction of Nicotinic Receptor-Regulated Signaling by Chronic Ethanol in Pancreatic Cancer Cells and Normal Duct Epithelia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Prev Res (Phila). 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1940-6207.CAPR-12-0388

AUTORES / AUTHORS:  - Al-Wadei MH; Al-Wadei HA; Schuller HM

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: 1Experimental Oncology Laboratory, Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee; and 2Sana’a University, Sana’a, Yemen.

RESUMEN / SUMMARY:  - Pancreatic cancer has a high mortality rate and alcoholism is a risk factor independent of smoking. We have shown that nicotinic acetylcholine receptors (nAChR) regulate pancreatic ductal epithelia and pancreatic ductal adenocarcinoma (PDAC) cells in an autocrine fashion by stimulating their production of the stress neurotransmitters noradrenaline and adrenaline that signal through beta-adrenergic receptors (beta-AR). Our current study has investigated the modulation of this autocrine regulatory loop by chronic ethanol and explored the  potential prevention of these effects by gamma-amino butyric acid (GABA).Using MTT assays, cell migration assays, Western blotting, immunoassays, and gene knockdown of individual nAChRs in two PDAC cell lines and in immortalized human pancreatic duct epithelial cells, our data show that treatment for seven days with ethanol induced the protein expression and sensitivity of nAChRs alpha3, alpha5, and alpha7 resulting in increased production of noradrenaline and adrenaline, which drive proliferation and migration via cyclic AMP (cAMP)-dependent signaling downstream of beta-ARs. Treatment with GABA prevented  all of these responses to chronic ethanol, reducing cell proliferation and migration below base levels in untreated cells.Our findings suggest that alcoholism induces multiple cAMP-dependent PDAC stimulating signaling pathways by upregulating the protein expression and sensitivity of nAChRs that regulate stress neurotransmitter production. Moreover, our data identify GABA as a promising agent for the prevention of PDAC in individuals at risk due to chronic  alcohol consumption. Cancer Prev Res; 1-10. ©2012 AACR.

----------------------------------------------------

[285]

TÍTULO / TITLE:  - Successful adjuvant bi-weekly gemcitabine chemotherapy for pancreatic cancer without impairing patients’ quality of life.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Surg Oncol. 2013 Jan 9;11(1):3. doi: 10.1186/1477-7819-11-3.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-11-3

AUTORES / AUTHORS:  - Toyama Y; Yoshida S; Saito R; Kitamura H; Okui N; Miyake R; Ito R; Son K; Usuba T; Nojiri T; Yanaga K

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, The Jikei University Kashiwa Hospital, 163-1, Kashiwashita, Kashiwa City, Chiba Prefecture, 277-8567, Japan. yoichitoyama@jikei.ac.jp.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Although adjuvant gemcitabine (GEM) chemotherapy for pancreatic cancer is standard, the quality of life (QOL) in those patients is still impaired by the standard regimen of GEM. Therefore, we studied whether mild dose-intensity adjuvant chemotherapy with bi-weekly GEM administration could provide a survival benefit with acceptable QOL to the patients with pancreatic cancer. METHODS: After a phase I trial, an adjuvant bi-weekly 1,000 mg/m2 of GEM  chemotherapy was performed in 58 patients with pancreatic cancer for at least 12  courses (Group A). In contrast, 36 patients who declined the adjuvant bi-weekly GEM chemotherapy underwent traditional adjuvant 5FU-based chemotherapy (Group B). Careful periodical follow-ups for side effects of GEM and disease recurrence, and assessment of patients’ QOL using the EORTC QOL questionnaire (QLQ-C30) and pancreatic cancer-specific supplemental module (QLQ-PAN26) were performed. Retrospectively, the degree of side effects, patients’ QOL, compliance rate, disease-free survival (DFS), and overall survival (OS) in Group A were compared with those in Group B. RESULTS: No severe side effects (higher than Grade 2 according to the common toxicity criteria of ECOG) were observed, except for patients in Group B, who were switched to the standard GEM chemotherapy. Patients’ QOL was better in Group A than B (fatigue: 48.9 +/- 32.1 versus 68.1 +/- 36.3, nausea and vomiting: 26.8 +/- 20.4 versus 53.7 +/- 32.6, diarrhea: 21.0 +/- 22.6 versus 53.9 +/- 38.5, difficulty gaining weight: 49.5 +/- 34.4 versus 67.7 +/- 40.5, P < 0.05). Compliance rates in Groups A and B were 93% and 47%. There was a significant difference in the median DFS between both groups (Group A : B =12.5 : 6.6 months, P < 0.001). The median OS of Group A was prolonged markedly compared with Group B (20.2 versus 11.9 months, P < 0.005). For OS between both groups, univariate analysis revealed no statistical difference in 69-year-old or under females, and T1-2 factors, moreover, multivariate analysis indicated three factors, such as bi-weekly adjuvant GEM chemotherapy, T2 or less, and R0. CONCLUSIONS: Adjuvant chemotherapy with bi-weekly GEM offered not only the advantage of survival benefits but the excellent compliance with acceptable QOL for postoperative pancreatic cancer patients.

----------------------------------------------------

[286]

TÍTULO / TITLE:  - Hypoxia-Induced Aggressiveness of Pancreatic Cancer Cells Is Due to Increased Expression of VEGF, IL-6 and miR-21, Which Can Be Attenuated by CDF Treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e50165. doi: 10.1371/journal.pone.0050165. Epub 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0050165

AUTORES / AUTHORS:  - Bao B; Ali S; Ahmad A; Azmi AS; Li Y; Banerjee S; Kong D; Sethi S; Aboukameel A; Padhye SB; Sarkar FH

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, United States of America.

RESUMEN / SUMMARY:  - Hypoxia is known to play critical roles in cell survival, angiogenesis, tumor invasion, and metastasis. Hypoxia mediated over-expression of hypoxia-inducible factor (HIF) has been shown to be associated with therapeutic resistance, and contributes to poor prognosis of cancer patients. Emerging evidence suggest that  hypoxia and HIF pathways contributes to the acquisition of epithelial-to-mesenchymal transition (EMT), maintenance of cancer stem cell (CSC) functions, and also maintains the vicious cycle of inflammation-all which lead to therapeutic resistance. However, the precise molecular mechanism(s) by which hypoxia/HIF drives these events are not fully understood. Here, we show, for the  first time, that hypoxia leads to increased expression of VEGF, IL-6, and CSC signature genes Nanog, Oct4 and EZH2 consistent with increased cell migration/invasion and angiogenesis, and the formation of pancreatospheres, concomitant with increased expression of miR-21 and miR-210 in human pancreatic cancer (PC) cells. The treatment of PC cells with CDF, a novel synthetic compound inhibited the production of VEGF and IL-6, and down-regulated the expression of Nanog, Oct4, EZH2 mRNAs, as well as miR-21 and miR-210 under hypoxia. CDF also led to decreased cell migration/invasion, angiogenesis, and formation of pancreatospheres under hypoxia. Moreover, CDF decreased gene expression of miR-21, miR-210, IL-6, HIF-1alpha, VEGF, and CSC signatures in vivo in a mouse orthotopic model of human PC. Collectively, these results suggest that the anti-tumor activity of CDF is in part mediated through deregulation of tumor hypoxic pathways, and thus CDF could become a novel, and effective anti-tumor agent for PC therapy.

----------------------------------------------------

[287]

TÍTULO / TITLE:  - Phase I Study of Oxaliplatin in Combination with Gemcitabine, Irinotecan, and 5-Fluorouracil/Leucovorin (G-FLIE) in Patients with Metastatic Solid Tumors Including Adenocarcinoma of the Pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Cancer. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12029-012-9466-2

AUTORES / AUTHORS:  - Olszewski AJ; Grossbard ML; Chung MS; Chalasani SB; Malamud S; Mirzoyev T; Kozuch PS

INSTITUCIÓN / INSTITUTION:  - St. Luke’s-Roosevelt Hospital Center, Continuum Cancer Centers of New York, 10th  Ave and 59th St, New York, NY, 10019, USA.

RESUMEN / SUMMARY:  - PURPOSE: The aims of this study were to establish the maximum tolerated dose (MTD) of oxaliplatin in combination with fixed doses of gemcitabine, irinotecan,  and 5-fluorouracil/leucovorin (G-FLIE) in solid tumors, including advanced pancreatic cancer, and to evaluate the toxicity of the regimen. METHODS: Patients with metastatic solid tumors were treated with a regimen consisting of gemcitabine (500 mg/m(2) by fixed-dose-rate infusion), irinotecan (120 mg/m(2)),  leucovorin 300 mg, bolus/infusion 5-fluorouracil (400 and 1,500 mg/m2, respectively), and oxaliplatin at doses from 50 to 85 mg/m(2) according to the escalation schema. Treatment was repeated every 14 days. RESULTS: The study enrolled 25 patients with a median age of 64 years and median Karnofsky performance score of 80. Patients had metastatic adenocarcinomas of pancreas (n = 9), as well as gastroesointestinal, hepatobiliary, or unknown primary tumors. With only one dose limiting toxicity (neutropenia and constipation), the MTD of oxaliplatin was not reached up to the pre-specified maximum level of 85 mg/m(2).  Other toxicities predictably included cytopenias, fatigue, sensory neuropathy, nausea/vomiting, diarrhea, and constipation. Four partial responses and ten disease stabilizations were observed. The overall median time to disease progression was 17 weeks (2-110 weeks) with median overall survival of 31.5 weeks (7-139 weeks). CONCLUSIONS: G-FLIE is a tolerable multi-agent chemotherapy regimen with the oxaliplatin dose up to 85 mg/m(2). The combination of full-dose  oxaliplatin with gemcitabine, irinotecan, and 5-fluorouracil is feasible with attenuated doses of the drugs, but further optimization is necessary before assessment of efficacy.

----------------------------------------------------

[288]

TÍTULO / TITLE:  - CD271(+) Subpopulation of Pancreatic Stellate Cells Correlates with Prognosis of  Pancreatic Cancer and Is Regulated by Interaction with Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52682. doi: 10.1371/journal.pone.0052682. Epub 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052682

AUTORES / AUTHORS:  - Fujiwara K; Ohuchida K; Mizumoto K; Shindo K; Eguchi D; Kozono S; Ikenaga N; Ohtsuka T; Takahata S; Aishima S; Tanaka M

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

RESUMEN / SUMMARY:  - Pancreatic stellate cells (PSCs) play a crucial role in the aggressive behavior of pancreatic cancer. Although heterogeneity of PSCs has been identified, the functional differences remain unclear. We characterized CD271(+) PSCs in human pancreatic cancer. Immunohistochemistry for CD271 was performed for 31 normal pancreatic tissues and 105 pancreatic ductal adenocarcinomas (PDACs). We performed flow cytometry and quantitative RT-PCR, and assessed CD271 expression in PSCs isolated from pancreatic tissues and the changes in CD271 expression in PSCs cocultured with cancer cells. We also investigated the pattern of CD271 expression in a SCID mouse xenograft model. In the immunohistochemical analyses,  the CD271-high staining rates in pancreatic stroma in normal pancreatic tissues and PDACs were 2/31 (6.5%) and 29/105 (27.6%), respectively (p = 0.0069). In PDACs, CD271(+) stromal cells were frequently observed on the edge rather than the center of the tumors. Stromal CD271 high expression was associated with a good prognosis (p = 0.0040). Flow cytometric analyses demonstrated CD271-positive rates in PSCs were 0-2.1%. Quantitative RT-PCR analyses revealed that CD271 mRNA  expression was increased in PSCs after coculture with pancreatic cancer cells. However, the level of CD271 mRNA expression subsequently decreased after the transient increase. Furthermore, CD271 mRNA expression was decreased in PSCs migrating toward pancreatic cancer cells through Matrigel. In the xenograft model, CD271(+) PSCs were present at tumor margins/periphery and were absent in the tumor core. In conclusion, CD271 was expressed in PSCs around pancreatic tumors, but not in the center of the tumors, and expression decreased after long  coculture with pancreatic cancer cells or after movement toward pancreatic cancer cells. These findings suggest that CD271(+) PSCs appear at the early stage of pancreatic carcinogenesis and that CD271 expression is significantly correlated with a better prognosis in patients with PDAC.

----------------------------------------------------

[289]

TÍTULO / TITLE:  - Pancreatic Tumors and Immature Immunosuppressive Myeloid Cells in Blood and Spleen: Role of Inhibitory Co-Stimulatory Molecules PDL1 and CTLA4. An In Vivo and In Vitro Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54824. doi: 10.1371/journal.pone.0054824. Epub 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054824

AUTORES / AUTHORS:  - Basso D; Fogar P; Falconi M; Fadi E; Sperti C; Frasson C; Greco E; Tamburrino D; Teolato S; Moz S; Bozzato D; Pelloso M; Padoan A; De Franchis G; Gnatta E; Facco M; Zambon CF; Navaglia F; Pasquali C; Basso G; Semenzato G; Pedrazzoli S; Pederzoli P; Plebani M

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, University of Padova, Padova, Italy.

RESUMEN / SUMMARY:  - BACKGROUND: Blood and spleen expansion of immature myeloid cells (IMCs) might compromise the immune response to cancer. We studied in vivo circulating and splenic T lymphocyte and IMC subsets in patients with benign and malignant pancreatic diseases. We ascertained in vitro whether pancreatic adenocarcinoma (PDAC)-associated IMC subsets are induced by tumor-derived soluble factors and whether they are immunosuppressive focusing on the inhibitory co-stimulatory molecules PDL1 and CTLA4. METHODOLOGY AND PRINCIPAL FINDINGS: 103 pancreatic and/or splenic surgical patients were enrolled including 52 PDAC, 10 borderline and 10 neuroendocrine tumors (NETs). Lymphocytes and IMCs were analysed by flow cytometry in blood, in spleen and in three PDAC cell conditioned (CM) or non conditioned PBMC. PDL1 and CTLA4 were studied in 30 splenic samples, in control and conditioned PBMC. IMCs were FACS sorted and co-coltured with allogenic T lymphocytes. In PDAC a reduction was found in circulating CD8(+) lymphocytes (p = 0.004) and dendritic cells (p = 0.01), which were reduced in vitro by one PDAC CM (Capan1; p = 0.03). Blood myeloid derived suppressive cells (MDSCs) CD33(+)CD14(-)HLA-DR(-) were increased in PDAC (p = 0.022) and were induced in vitro by BxPC3 CM. Splenic dendritic cells had a higher PDL1 expression (p = 0.007), while CD33(+)CD14(+)HLA-DR(-) IMCs had a lower CTLA4 expression (p = 0.029) in PDAC patients. In vitro S100A8/A9 complex, one of the possible inflammatory mediators of immune suppression in PDAC, induced PDL1 (p = 0.018) and reduced CTLA4 expression (p = 0.028) among IMCs. IMCs not expressing CTLA4 were demonstrated to be immune suppressive. CONCLUSION: In PDAC circulating dendritic and cytotoxic T cells are reduced, while MDSCs are increased and this might favour tumoral growth and progression. The reduced CTLA4 expression found among splenic IMCs of PDAC patients was demonstrated to characterize an immune suppressive phenotype and to be consequent to the direct exposure of myeloid cells to pancreatic cancer derived products, S100A8/A9 complex in particular.

----------------------------------------------------

[290]

TÍTULO / TITLE:  - Effective combination gene therapy using CEACAM6-shRNA and the fusion suicide gene yCDglyTK for pancreatic carcinoma in vitro.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Ther Med. 2013 Jan;5(1):155-161. Epub 2012 Oct 30.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.774

AUTORES / AUTHORS:  - Long H; Li Q; Wang Y; Li Q; Liu T; Peng J

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

RESUMEN / SUMMARY:  - The incidence of pancreatic carcinoma, a gastrointestinal malignancy, is on the increase and effective therapeutic strategies are therefore required. This study  aimed to construct a recombinant plasmid pcDNA3.1(-) shCEACAM6-yCDglyTK from CEACAM6 targeting shRNA and the fusion suicide gene yCDglyTK for inhibition of SW1990 human pancreatic carcinoma cell growth and invasion. A plasmid containing  hU6 promoter and CEACAM6 targeting short hairpin RNA (CEACAM6-shRNA) frame was constructed. It was subcloned to a CEA promoter-driven fusion suicide gene pcDNA3.1(-)yCDglyTK. The recombinant plasmid pcDNA3.1(-) shCEACAM6-yCDglyTK was identified by restriction endonuclease analysis and DNA sequencing. The recombinant plasmid was delivered into SW1990 human pancreatic carcinoma cells, the mRNA and protein expression of yCDglyTK and CEACAM6 was examined by RT-PCR, western blot analysis and immunofluorescence. SW1990 cells were treated with the  prodrug 5-fluorocytosine (5-FC), and the cell viability was evaluated using the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. The invasiveness and migration of SW1990 cells were evaluated by transwell migration  assays. The restriction endonuclease analysis and DNA sequencing confirmed the construction of the recombinant plasmid pcDNA3.1(-) shCEACAM6-yCDglyTK. Reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis outcomes showed that yCDglyTK was expressed in SW1990 cells and expression of CEACAM6 in SW1990 cells was significantly knocked down. MTT assay showed that the mean viability of SW1990 cells was significantly reduced after administration of  the prodrug 5-FC in vitro. Transwell migration assays showed that invasion and migration action of SW1990 cells was significantly inhibited. In conclusion, recombinant plasmid pcDNA3.1(-) shCEACAM6-yCDglyTK was successfully constructed.  The recombinant plasmid may therefore serve as a novel gene therapy approach for  pancreatic carcinoma.

----------------------------------------------------

[291]

TÍTULO / TITLE:  - The technical feasibility of an image-guided intensity-modulated radiotherapy (IG-IMRT) to perform a hypofractionated schedule in terms of toxicity and local control for patients with locally advanced or recurrent pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiat Oncol. 2012 Dec 5;7:203. doi: 10.1186/1748-717X-7-203.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-7-203

AUTORES / AUTHORS:  - Son SH; Song JH; Choi BO; Kang YN; Lee MA; Kang KM; Jang HS

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul, Korea. hsjang11@catholic.ac.kr.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: The purpose of this study was to evaluate the technical feasibility of an image-guided intensity modulated radiotherapy (IG-IMRT) using involved-field technique to perform a hypofractionated schedule for patients with locally advanced or recurrent pancreatic cancer. METHODS: From May 2009 to November 2011, 12 patients with locally advanced or locally recurrent pancreatic  cancer received hypofractionated CCRT using TomoTherapy Hi-Art with concurrent and sequential chemotherapy at Seoul St. Mary’s Hospital, the Catholic University of Korea. The total dose delivered was 45 Gy in 15 fractions or 50 Gy in 20 fractions. The target volume did not include the uninvolved regional lymph nodes. Treatment planning and delivery were performed using the IG-IMRT technique. The follow-up duration was a median of 31.1 months (range: 5.7-36.3 months). RESULTS: Grade 2 or worse acute toxicities developed in 7 patients (58%). Grade 3 or worse gastrointestinal and hematologic toxicity occurred in 0% and 17% of patients, respectively. In the response evaluation, the rates of partial response and stable disease were 58% and 42%, respectively. The rate of local failure was 8% and no regional failure was observed. Distant failure was the main cause of treatment failure. The progression-free survival and overall survival durations were 7.6 and 12.1 months, respectively. CONCLUSION: The involved-field technique  and IG-IMRT delivered via a hypofractionated schedule are feasible for patients with locally advanced or recurrent pancreatic cancer.

----------------------------------------------------

[292]

TÍTULO / TITLE:  - Clinical Value of Dual-energy CT in Detection of Pancreatic Adenocarcinoma: Investigation of the Best Pancreatic Tumor Contrast to Noise Ratio.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin Med Sci J. 2013 Jan;27(4):207-12.

AUTORES / AUTHORS:  - He YL; Zhang DM; Xue HD; Jin ZY

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

RESUMEN / SUMMARY:  - Objective To quantitatively compare and determine the best pancreatic tumor contrast to noise ratio (CNR) in different dual-energy derived datasets. Methods  In this retrospective, single center study, 16 patients (9 male, 7 female, average age 59.4+/-13.2 years) with pathologically diagnosed pancreatic cancer were enrolled. All patients received an abdominal scan using a dual source CT scanner 7 to 31 days before biopsy or surgery. After injection of iodine contrast agent, arterial and pancreatic parenchyma phase were scanned consequently, using  a dual-energy scan mode (100 kVp/230 mAs and Sn 140 kVp/178 mAs) in the pancreatic parenchyma phase. A series of derived dual-energy datasets were evaluated including non-liner blending (non-linear blending width 0-500 HU; blending center -500 to 500 HU), mono-energetic (40-190 keV), 100 kVp and 140 kVp. On each datasets, mean CT values of the pancreatic parenchyma and tumor, as  well as standard deviation CT values of subcutaneous fat and psoas muscle were measured. Regions of interest of cutaneous fat and major psoas muscle of 100 kVp  and 140 kVp images were calculated. Best CNR of subcutaneous fat (CNRF) and CNR of the major psoas muscle (CNRM) of non-liner blending and mono-energetic datasets were calculated with the optimal mono-energetic keV setting and the optimal blending center/width setting for the best CNR. One Way ANOVA test was used for comparison of best CNR between different dual-energy derived datasets. Results The best CNRF (4.48+/-1.29) was obtained from the non-liner blending datasets at blending center -16.6+/-103.9 HU and blending width 12.3+/-10.6 HU. The best CNRF (3.28+/-0.97) was obtained from the mono-energetic datasets at 73.3+/-4.3 keV. CNRF in the 100 kVp and 140 kVp were 3.02+/-0.91 and 1.56+/-0.56  respectively. Using fat as the noise background, all of these images series showed significant differences (P<0.01) except best CNRF of mono-energetic image  sets vs. CNRF of 100 kVp image (P=0.460). Similar results were found using muscle as the noise background (mono-energetic image vs. 100 kVp image: P=0.246; mono-energetic image vs. non-liner blending image: P=0.044; others: P<0.01). Conclusion Compared with mono-energetic datasets and low kVp datasets, non-linear blending image at automatically chosen blending width/window provides better tumor to the pancreas CNR, which might be beneficial for better detection of pancreatic tumors.

 

----------------------------------------------------

[293]

TÍTULO / TITLE:  - Safety and efficacy of sunitinib in patients with unresectable pancreatic neuroendocrine tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Med Insights Oncol. 2012;6:381-93. doi: 10.4137/CMO.S7350. Epub 2012 Nov 20.

            ●● Enlace al texto completo (gratuito o de pago) 4137/CMO.S7350

AUTORES / AUTHORS:  - Wiedmann MW; Mossner J

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine I, St. Mary’s Hospital, Berlin, Germany. ; Division of Gastroenterology and Rheumatology, Department of Medicine, Neurology  and Dermatology, University Hospital of Leipzig, Leipzig, Germany.

RESUMEN / SUMMARY:  - Pancreatic neuroendocrine tumors (PNETs) are becoming increasingly common, with the majority of patients presenting with either lymph node involvement or metastatic disease, thus requiring systemic therapy. Targeted therapy is a type of medication that blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth rather than by simply interfering with rapidly dividing cells (eg, with traditional chemotherapy). In this review article, pharmacologic inhibition of multiple targets including vascular endothelial growth factor receptor (VEGF-R), platelet-derived growth factor receptor (PDGF-R), stem cell factor receptor (c-KIT-R), FML-like tyrosine kinase-3 receptor (FLT3-R), colony stimulating factor 1 receptor (CSF1-R), and glial cell-line derived neurotrophic factor receptor (RET-R) with sunitinib in patients with unresectable PNETs is discussed. Phase III data indicate that additional treatment with sunitinib can improve prognosis in these patients.

----------------------------------------------------

[294]

TÍTULO / TITLE:  - Peripherally-inserted central catheter-related fungemia due to hansenula polymorpha in a patient with pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Glob Infect Dis. 2012 Oct;4(4):220-1. doi: 10.4103/0974-777X.103903.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0974-777X.103903

AUTORES / AUTHORS:  - Garbati MA

INSTITUCIÓN / INSTITUTION:  - Division of Infectious Diseases, Department of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia.

RESUMEN / SUMMARY:  - The methylotrophic yeast Hansenula polymorpha, used mainly as an industrial agent in the production of pharmaceuticals, has rarely been reported to cause disease.  The case of a 47-year old Pilipino male with pancreatic cancer presented here is  the second reported in the literature. Major risk factors for this infection included underlying malignancy, abdominal surgery and the use of a peripherally-inserted central catheter for total parenteral nutrition. He was successfully treated with a two-week’s course of voriconazole.

----------------------------------------------------

[295]

TÍTULO / TITLE:  - Mucinous cystic neoplasm of the pancreas with neuroendocrine cells and malignant  stroma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Saudi Med J. 2013 Jan;34(1):80-5.

AUTORES / AUTHORS:  - Asberry DE; Youngberg GA; Al-Abbadi MA

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Laboratory Medicine, James H. Quillen VA Medical Center, East Tennessee State University College of Medicine, Johnson City, Tennessee, United States of America.

RESUMEN / SUMMARY:  - Mucinous cystic neoplasms (MCN) with malignant sarcomatous stroma are rare aggressive tumors and there are few recorded cases. We report a case of MCN that  had adenocarcinoma in situ and invasive adenocarcinoma with foci of sarcomatous stroma in a 40-year-old woman. Clear transition from adenocarcinoma areas into sarcomatoid foci was noted. The stromal component showed immunoreactivity for CK7 and Cam 5.2 supporting epithelial origin of the sarcomatoid areas. Associated areas of cytologically benign MCN epithelium were present and were immunoreactive for positive staining with pan-cytokeratin (AE1/AE3), cytokeratin 7 (CK 7), cytokeratin 20 (CK 20), pan-cytokeratin (Cam 5.2), epithelial membrane antigen (EMA), muscle specific actin (MSA), and carcino-embryonic antigen (CEA). Interestingly, definite scattered pear-shaped neuroendocrine cells, as evidenced  by strong immunoreactivity for chromogranin and synaptophysin, were identified in the cytologically benign MCN lining but not in the malignant epithelial component. We found that these tumor cells probably arise from a single precursor cell capable of divergent differentiation.

 

----------------------------------------------------

[296]

TÍTULO / TITLE:  - Clinical and CT imaging features of pancreatic acinar cell carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiol Med. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11547-012-0908-5

AUTORES / AUTHORS:  - Hu S; Hu S; Wang M; Wu Z; Miao F

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197, Ruijin 2nd Road, Shanghai, 200025, China.

RESUMEN / SUMMARY:  - PURPOSE: This study was undertaken to analyse the clinical characteristics and computed tomography (CT) imaging features of patients with pancreatic acinar cell carcinoma and to clarify characteristic imaging features. MATERIALS AND METHODS:  Clinical and CT imaging records of ten patients with pancreatic acinar cell carcinoma (three women and seven men; mean age, 58 years) examined using multidetector CT scanners were retrospectively studied. CT features emphasised included lesion location, size, shape, margin, solid or cystic component, density and enhancement. Imaging results were correlated with intraoperative surgical and pathological results. RESULTS: Lesions were distributed throughout the pancreatic head (n=3), body (n=3), tail (n=2) and both body and tail (n=2). The average diameter was 6.1 cm, varying from 2.3 cm to 15.8 cm. The tumours were round or oval (n=7) or lobular (n=3). Seven tumours appeared as enhanced solid pancreatic  masses, with the large masses having hypodense areas; three had >75 % cystic component; seven (70%), including four solid and three cystic masses, had wellcircumscribed or partially well-defined thin, enhanced encapsulation. After contrast injection, the masses presented heterogeneous enhancement. CONCLUSIONS:  Acinar cell carcinoma should always be considered when a large pancreatic mass with typical imaging is found in solid masses with variably sized central cystic  areas or cystic masses.

----------------------------------------------------

[297]

TÍTULO / TITLE:  - A novel missense mutation (N78D) in a family with von Hippel-Lindau disease with  central nervous system haemangioblastomas, pancreatic and renal cysts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Fam Cancer. 2012 Dec 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10689-012-9586-7

AUTORES / AUTHORS:  - Cingoz S; van der Luijt RB; Kurt E; Apaydin M; Akkol I; Ozgen MH

INSTITUCIÓN / INSTITUTION:  - Department of Medical Biology and Genetic, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

RESUMEN / SUMMARY:  - von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome caused by mutations in the VHL tumor suppressor gene. In a family with VHL, we identified a novel missense mutation (N78D), which affects a fully conserved residue in the VHL protein. Interestingly, several other missense mutations reported at same codon in the VHL protein that might be associated with a low risk of renal cell carcinoma (RCC) but not pheochromocytoma appear to be associated with a VHL type  1 phenotype. At the moment, RCC is present in none of the affected mutation carriers in the family described here. In contrast to other missense changes at codon 78, the change in our VHL family is predicted to have a mild effect on VHL  function, which apparently is insufficient to cause predisposition to RCC. Our findings suggest that the risk of RCC in VHL is attributable to the severity of the amino acid substitution at this particular codon in the VHL protein.

----------------------------------------------------

[298]

TÍTULO / TITLE:  - Tanshinone IIA inhibits the growth of pancreatic cancer BxPC3 cells by decreasing protein expression of TCTP, MCL1 and BclxL.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Med Report. 2013 Jan 25. doi: 10.3892/mmr.2013.1290.

            ●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1290

AUTORES / AUTHORS:  - Huang CY; Chiu TL; Kuo SJ; Chien SY; Chen DR; Su CC

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C.

RESUMEN / SUMMARY:  - Pancreatic cancer remains a challenging disease worldwide. Tanshinone IIA (TanIIA) is one of the active constituents of Danshen (Radix Salviae miltiorrhizae). TanIIA has been hypothesized to inhibit numerous human cancer cells by various molecular mechanisms. However, the efficacy and molecular mechanism of TanIIA action in pancreatic cancer has not been well studied. In the present study, the cytotoxicity of TanIIA in human pancreatic cancer BxPC3 cells  was evaluated by MTT assay. Cell cycle analysis of BxPC3 cells treated with TanIIA was performed by flow cytometry (FACS). Protein expression levels of TCTP, Mcl1, BclxL, Bax and Caspase3 in BxPC3 cells were measured by western blot analysis. The results revealed that TanIIA inhibited BxPC3 cells in a time and dosedependent manner. FACS analysis demonstrated that TanIIA increases the rate of subG1 phase. BxPC3 cells treated with TanIIA were identified to upregulate protein expression of Bax and Caspase3 and downregulate expression of TCTP, Mcl1  and BclxL. These results indicate that TanIIA may inhibit BxPC3 human pancreatic  cancer cells through the induction of apoptosis by decreasing protein expression  of TCTP, Mcl1 and BclxL and increasing Bax expression in vitro. The chemotherapeutic potential of TanIIA for human pancreatic cancer warrants further study.

----------------------------------------------------

[299]

TÍTULO / TITLE:  - Non-invasive measurement of liver and pancreas fibrosis in patients with cystic fibrosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cyst Fibros. 2013 Jan 26. pii: S1569-1993(13)00006-4. doi: 10.1016/j.jcf.2012.12.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jcf.2012.12.013

AUTORES / AUTHORS:  - Friedrich-Rust M; Schlueter N; Smaczny C; Eickmeier O; Rosewich M; Feifel K; Herrmann E; Poynard T; Gleiber W; Lais C; Zielen S; Wagner TO; Zeuzem S; Bojunga J

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine 1, J.W. Goethe-University Hospital, Frankfurt, Germany. Electronic address: Mireen.Friedrich-Rust@kgu.de.

RESUMEN / SUMMARY:  - BACKGROUND: Patients with cystic fibrosis (CF) have a relevant morbidity and mortality caused by CF-related liver-disease. While transient elastography (TE) is an established elastography method in hepatology centers, Acoustic-Radiation-Force-Impulse (ARFI)-Imaging is a novel ultrasound-based elastography method which is integrated in a conventional ultrasound-system. The  aim of the present study was to evaluate the prevalence of liver-fibrosis in patients with CF using TE, ARFI-imaging and fibrosis blood tests. METHODS: 106 patients with CF were prospectively included in the present study and received ARFI-imaging of the left and right liver-lobe, ARFI of the pancreas TE of the liver and laboratory evaluation. RESULTS: The prevalence of liver-fibrosis according to recently published best practice guidelines for CFLD was 22.6%. Prevalence of significant liver-fibrosis assessed by TE, ARFI-right-liver-lobe, ARFI-left-liver-lobe, Fibrotest, Fibrotest-corrected-by-haptoglobin was 17%, 24%, 40%, 7%, and 16%, respectively. The best agreement was found for TE, ARFI-right-liver-lobe and Fibrotest-corrected-by-haptoglobin. Patients with pancreatic-insufficiency had significantly lower pancreas-ARFI-values as compared to patients without. CONCLUSIONS: ARFI-imaging and TE seem to be promising non-invasive methods for detection of liver-fibrosis in patients with CF.

----------------------------------------------------

[300]

TÍTULO / TITLE:  - Recurrent acute pancreatitis in a patient with wirsungocele and neuroendocrine tumor of ampulla of vater.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JOP. 2013 Jan 10;14(1):99-101. doi: 10.6092/1590-8577/1310.

AUTORES / AUTHORS:  - Dhir V; Joshi N; Vivekanandarajah S; Bhandari S; Bapat M; Maydeo A

INSTITUCIÓN / INSTITUTION:  - Baldota Institute of Digestive Sciences. Mumbai, India. vinaydhir@gmail.com.

RESUMEN / SUMMARY:  - CONTEXT: Wirsungocele has recently been shown to be associated with acute recurrent, severe necrotizing pancreatitis and chronic pancreatitis or chronic pain in abdomen. Till to date there is no report on association of wirsungocele with an ampullary neuroendocrine tumor, and recurrent pancreatitis. CASE REPORT:  We report a first ever case of wirsungocele diagnosed on EUS, its association with neuroendocrine tumor of ampulla and recurrent acute pancreatitis. CONCLUSION: This case report highlights the diagnostic utility of EUS in diagnosing small ampullary pathology like wirsungocele and neuroendocrine tumor.

----------------------------------------------------

[301]

TÍTULO / TITLE:  - Inhibiting the Interaction of cMET and IGF-1R with FAK Effectively Reduces Growth of Pancreatic Cancer Cells in Vitro and in Vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Agents Med Chem. 2012 Dec 14.

AUTORES / AUTHORS:  - Ucar DA; Magis AT; He DH; Lawrence NJ; Sebti SM; Kurenova E; Zajac-Kaye M; Zhang J; Hochwald SN

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA. steven.hochwald@roswellpark.org.

RESUMEN / SUMMARY:  - Pancreatic cancer is one of the most lethal diseases with no effective treatment. Previously, we have shown that FAK is overexpressed in pancreatic cancer and plays a key role in cancer cell survival and proliferation. FAK has been shown to interact with growth factor receptors including cMET and IGF-1R. As a novel therapeutic approach, we targeted the protein interaction of FAK with growth factor receptors to block tumor growth, alter signaling pathways and sensitize cells to chemotherapy. We have selected a small molecule compound (INT2-31) that  decreases phosphorylation of AKT via disrupting interaction of FAK with cMET and  IGF-1R. Our results demonstrate that interaction of a small molecule compound with FAK decreases phosphorylation of FAK Y397 while increasing FAK Y407 phosphorylation, without inhibiting the kinase activity of FAK and dramatically reduces downstream signaling to AKT. Our lead compound, INT2-31, demonstrates significant inhibition of tumor cell growth in two orthotopic models of pancreatic cancer. In addition, INT2-31increases sensitivity to gemcitabine chemotherapy in a direct fresh biopsy xenograft model of pancreatic cancer growth.

----------------------------------------------------

[302]

TÍTULO / TITLE:  - Unicentric Castleman’s Disease Masquerading Pancreatic Neoplasm.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Oncol Med. 2012;2012:793403. doi: 10.1155/2012/793403. Epub 2012 Nov 25.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/793403

AUTORES / AUTHORS:  - Jain S; Chatterjee S; Swain JR; Rakshit P; Chakraborty P; Sinha S

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, Medical College Hospital, Kolkata, 88 College Street, Kolkata 700073, India.

RESUMEN / SUMMARY:  - Castleman’s disease is a rare nonclonal proliferative disorder of the lymph nodes with an unknown etiology. Common locations of Castleman’s disease are mediastinum, neck, axilla, and abdomen. Castleman’s disease of a peripancreatic location masquerading as pancreatic neoplasm is an even rarer entity. On search of published data, we came across about 17 cases published on peripancreatic Castleman’s disease until now. Here we are reporting a case of retropancreatic Castleman’s disease masquerading as retroperitoneal neoplasm in a 46-year-old male patient.

----------------------------------------------------

[303]

TÍTULO / TITLE:  - Class I and Class II Histone Deacetylases Are Potential Therapeutic Targets for Treating Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52095. doi: 10.1371/journal.pone.0052095. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052095

AUTORES / AUTHORS:  - Wang G; He J; Zhao J; Yun W; Xie C; Taub JW; Azmi A; Mohammad RM; Dong Y; Kong W; Guo Y; Ge Y

INSTITUCIÓN / INSTITUTION:  - The State Engineering Laboratory of AIDS Vaccine, College of Life Science, Jilin  University, Changchun, China.

RESUMEN / SUMMARY:  - BACKGROUND: Pancreatic cancer is a highly malignant disease with an extremely poor prognosis. Histone deacetylase inhibitors (HDACIs) have shown promising antitumor activities against preclinical models of pancreatic cancer, either alone or in combination with chemotherapeutic agents. In this study, we sought to identify clinically relevant histone deacetylases (HDACs) to guide the selection  of HDAC inhibitors (HDACIs) tailored to the treatment of pancreatic cancer. METHODOLOGY: HDAC expression in seven pancreatic cancer cell lines and normal human pancreatic ductal epithelial cells was determined by Western blotting. Antitumor interactions between class I- and class II-selective HDACIs were determined by MTT assays and standard isobologram/CompuSyn software analyses. The effects of HDACIs on cell death, apoptosis and cell cycle progression, and histone H4, alpha-tubulin, p21, and gammaH2AX levels were determined by colony formation assays, flow cytometry analysis, and Western blotting, respectively. RESULTS: The majority of classes I and II HDACs were detected in the pancreatic cancer cell lines, albeit at variable levels. Treatments with MGCD0103 (a class I-selective HDACI) resulted in dose-dependent growth arrest, cell death/apoptosis, and cell cycle arrest in G2/M phase, accompanied by induction of p21 and DNA double-strand breaks (DSBs). In contrast, MC1568 (a class IIa-selective HDACI) or Tubastatin A (a HDAC6-selective inhibitor) showed minimal effects. When combined simultaneously, MC1568 significantly enhanced MGCD0103-induced growth arrest, cell death/apoptosis, and G2/M cell cycle arrest, while Tubastatin A only synergistically enhanced MGCD0103-induced growth arrest.  Although MC1568 or Tubastatin A alone had no obvious effects on DNA DSBs and p21  expression, their combination with MGCD0103 resulted in cooperative induction of  p21 in the cells. CONCLUSION: Our results suggest that classes I and II HDACs are potential therapeutic targets for treating pancreatic cancer. Accordingly, treating pancreatic cancer with pan-HDACIs may be more beneficial than class- or  isoform-selective inhibitors.

----------------------------------------------------

[304]

TÍTULO / TITLE:  - Genetics: Variants in SBF2 gene associated with survival in pancreatic adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Gastroenterol Hepatol. 2012 Dec 11;10(1):4. doi: 10.1038/nrgastro.2012.244. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrgastro.2012.244

AUTORES / AUTHORS:  - Franks I

----------------------------------------------------

[305]

TÍTULO / TITLE:  - Erratum to: Celastrol suppresses invasion of colon and pancreatic cancer cells through the downregulation of expression of CXCR4 chemokine receptor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Mol Med (Berl). 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00109-012-0987-8

AUTORES / AUTHORS:  - Yadav VR; Sung B; Prasad S; Kannappan R; Cho SG; Liu M; Chaturvedi MM; Aggarwal BB

INSTITUCIÓN / INSTITUTION:  - Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

----------------------------------------------------

[306]

TÍTULO / TITLE:  - GPC-1 may serve as a predictor of perineural invasion and a prognosticator of survival in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian J Surg. 2013 Jan;36(1):7-12. doi: 10.1016/j.asjsur.2012.08.001. Epub 2012 Sep 16.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.asjsur.2012.08.001

AUTORES / AUTHORS:  - Duan L; Hu XQ; Feng DY; Lei SY; Hu GH

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.

RESUMEN / SUMMARY:  - OBJECTIVE: The purpose of this study was to investigate the expression of glial cell derived neurotrophic factor (GDNF), glypican-1 (GPC-1), and matrix metalloproteinase-9 (MMP-9), and their association with clinicopathologic characteristics as well as prognostic significance in pancreatic cancer. METHODS: Immunohistochemical assessment of GDNF, GPC-1, and MMP-9 was performed in 62 cases of surgically resected pancreatic cancer. Perineural invasion in pancreatic cancer was observed by marking nerve fiber with S-100, while 16 normal pancreatic tissues were used as normal control. Correlations of GDNF, GPC-1 and MMP-9 expressions with clinicopathologic parameters were analyzed. A survival analysis  was performed to find the prognostic significance. RESULTS: The expressions of GDNF, GPC-1 and MMP-9 in pancreatic cancer tissue were significantly higher than  of those in normal pancreatic tissues (41/62 vs. 5/16 for GDNF, 35/62 vs. 2/16 for GPC-1, and 37/62 vs. 3/16 for MMP-9; p<0.01, respectively). The overexpression of GDNF, GPC-1, and MMP-9 in pancreatic cancer tissue was significantly related to the perineural invasion (p<0.05). Although the overexpression of these genes was related to poor survival, GPC-1 had an independent prognostic effect on overall survival. CONCLUSION: GPC-1 is significantly related to the perineural invasion of pancreatic cancer, holding some prognostic significance in patients with pancreatic cancer.

 

----------------------------------------------------

[307]

TÍTULO / TITLE:  - Group VIB Phospholipase A(2) promotes proliferation of INS-1 insulinoma cells and attenuates lipid peroxidation and apoptosis induced by inflammatory cytokines and oxidant agents.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oxid Med Cell Longev. 2012;2012:989372. doi: 10.1155/2012/989372. Epub 2012 Nov 11.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/989372

AUTORES / AUTHORS:  - Bao S; Song H; Tan M; Wohltmann M; Ladenson JH; Turk J

INSTITUCIÓN / INSTITUTION:  - Mass Spectrometry Resource, Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, Campus Box 8127, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.

RESUMEN / SUMMARY:  - Group VIB Phospholipase A(2) (iPLA(2)gamma) is distributed in membranous organelles in which beta-oxidation occurs, that is, mitochondria and peroxisomes, and is expressed by insulin-secreting pancreatic islet beta-cells and INS-1 insulinoma cells, which can be injured by inflammatory cytokines, for example, IL-1beta and IFN-gamma, and by oxidants, for example, streptozotocin (STZ) or t-butyl-hydroperoxide (TBHP), via processes pertinent to mechanisms of beta-cell  loss in types 1 and 2 diabetes mellitus. We find that incubating INS-1 cells with IL-1beta and IFN-gamma, with STZ, or with TBHP causes increased expression of iPLA(2)gamma mRNA and protein. We prepared INS-1 knockdown (KD) cell lines with reduced iPLA(2)gamma expression, and they proliferate more slowly than control INS-1 cells and undergo increased membrane peroxidation in response to cytokines  or oxidants. Accumulation of oxidized phospholipid molecular species in STZ-treated INS-1 cells was demonstrated by LC/MS/MS scanning, and the levels in  iPLA(2)gamma-KD cells exceeded those in control cells. iPLA(2)gamma-KD INS-1 cells also exhibited higher levels of apoptosis than control cells when incubated with STZ or with IL-1beta and IFN-gamma. These findings suggest that iPLA(2)gamma promotes beta-cell proliferation and that its expression is increased during inflammation or oxidative stress as a mechanism to mitigate membrane injury that  may enhance beta-cell survival.

----------------------------------------------------

[308]

TÍTULO / TITLE:  - A Cancer-Specific Variant of the SLCO1B3 Gene Encodes a Novel Human Organic Anion Transporting Polypeptide 1B3 (OATP1B3) Localized Mainly in the Cytoplasm of Colon and Pancreatic Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Pharm. 2013 Jan 7;10(1):406-16. doi: 10.1021/mp3005353. Epub 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 1021/mp3005353

AUTORES / AUTHORS:  - Thakkar N; Kim K; Jang ER; Han S; Kim K; Kim D; Merchant N; Lockhart AC; Lee W

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, United States.

RESUMEN / SUMMARY:  - OATP1B3 is a member of the OATP (organic anion transporting polypeptides) superfamily, responsible for mediating the transport of numerous endogenous and xenobiotic substances. Although initially reported to be exclusively expressed in the liver, several studies reported that OATP1B3 is frequently expressed in multiple types of cancers and may be associated with differing clinical outcomes. However, a detailed investigation on the expression and function of OATP1B3 protein in cancer has been lacking. In this study, we confirmed that colon and pancreatic cancer cells express variant forms of OATP1B3, different from OATP1B3  wild-type (WT) expressed in the normal liver. OATP1B3 variant 1 (V1), the most prevalent form among the variants, contains alternative exonic sequences (exon 2a) instead of exons 1 and 2 present in OATP1B3 WT. The translated product of OATP1B3 V1 is almost identical to OATP1B3 WT, with exception to the first 28 amino acids at the N-terminus. Exogenous expression of OATP1B3 V1 revealed that OATP1B3 V1 undergoes post-translational modifications and proteasomal degradation to a differing extent compared to OATP1B3 WT. OATP1B3 V1 showed only modest transport activity toward cholecystokin-8 (CCK-8, a prototype OATP1B3 substrate)  in contrast to OATP1B3 WT showing a markedly efficient uptake of CCK-8. Consistent with these results, OATP1B3 V1 was localized mainly in the cytoplasm with a much lower extent of trafficking to the surface membrane compared to OATP1B3 WT. In summary, our results demonstrate that colon and pancreatic cancer  cells express variant forms of OATP1B3 with only limited transport activity and different subcellular localization compared to OATP1B3 WT. These observed differences at the molecular and functional levels will be important considerations for further investigations of the biological and clinical significance of OATP1B3 expression in cancer.

----------------------------------------------------

[309]

TÍTULO / TITLE:  - Resveratrol induces apoptosis of pancreatic cancers cells by inhibiting miR-21 regulation of BCL-2 expression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Oncol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0999-4

AUTORES / AUTHORS:  - Liu P; Liang H; Xia Q; Li P; Kong H; Lei P; Wang S; Tu Z

INSTITUCIÓN / INSTITUTION:  - Department of Medical Laboratory, Chongqing University of Medical Science, Chongqing, China.

RESUMEN / SUMMARY:  - OBJECTIVE: Resveratrol is an edible polyphenolic phytoalexin present in different plant species and plays important role in inhibiting proliferation and inducing apoptosis of pancreatic cancer cells. In this paper, the mechanism of resveratrol on PANC-1, CFPAC-1 and MIA Paca-2 cells apoptosis was examined. METHODS: We first evaluated the effect of resveratrol on viability of PANC-1, CFPAC-1 and MIA Paca-2 cells using MTT assay. Next, we performed real-time PCR to assess the effect of resveratrol on miR-21 expression. We also used Western blot to measure  BCL-2 protein levels after down-regulation of miR-21 expression. Finally, we evaluated the effect of miR-21 on resveratrol-induced anti-tumor activity using miR-21 mimic. RESULTS: Resveratrol induced a significant inhibition of PANC-1, CFPAC-1 and MIA Paca-2 cells viability in a dose-dependent manner. Resveratrol also decreased the expression of miR-21. Besides, down-regulation of miR-21 expression can inhibit BCL-2 expression in PANC-1, CFPAC-1 and MIA Paca-2 cells.  Over-expression of miR-21 expression can reverse down-regulation of BCL-2 expression and apoptosis induced by resveratrol. CONCLUSIONS: In this study, we demonstrated that the effect of resveratrol on apoptosis is due to inhibiting miR-21 regulation of BCL-2 expression.

----------------------------------------------------

[310]

TÍTULO / TITLE:  - Dual inhibition of Janus and Src family kinases by novel indirubin derivative blocks constitutively-activated Stat3 signaling associated with apoptosis of human pancreatic cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Oncol. 2012 Nov 16. pii: S1574-7891(12)00122-6. doi: 10.1016/j.molonc.2012.10.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.molonc.2012.10.013

AUTORES / AUTHORS:  - Nam S; Wen W; Schroeder A; Herrmann A; Yu H; Cheng X; Merz KH; Eisenbrand G; Li H; Yuan YC; Jove R

INSTITUCIÓN / INSTITUTION:  - Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA. Electronic address: snam@coh.org.

RESUMEN / SUMMARY:  - Constitutively-activated JAK/Stat3 or Src/Stat3 signaling plays a crucial role in tumor cell survival, proliferation, angiogenesis and immune suppression. Activated JAK/Stat3 or Src/Stat3 has been validated as a promising molecular target for cancer therapy. However, prolonged inhibition of Src family kinases (SFKs) leads to reactivation of signal transducer and activator of transcript 3 (Stat3) and tumor cell survival through altered JAK/Stat3 interaction. This compensatory feedback suggests that dual inhibition of Janus kinases (JAKs) and SFKs might be a promising strategy for targeting downstream Stat3 signaling in the clinic. In this study, we identify that the natural product derivative E738 is a novel dual inhibitor of JAKs and SFKs. The IC(50) values of E738 against recombinant JAKs and SFKs in vitro are in the ranges of 0.7-74.1 nM and 10.7-263.9 nM, respectively. We observed that phosphorylation of both Jak2 and Src was substantially inhibited in the submicromolar range by E738 in cultured human pancreatic tumor cells, followed by blockade of downstream Stat3 activation. E738 down-regulated expression of the Stat3 target proteins Mcl-1 and survivin, associated with induction of apoptosis. Computational models and molecular dynamics simulations of E738/Tyk2 or E738/Src in silico suggest that E738 inhibits both tyrosine kinase 2 (Tyk2) and Src as an ATP-competitive ligand. Moreover, the planar E738 molecule demonstrates a strong binding affinity in the  compact ATP-binding site of Tyk2. In sum, E738 is the first dual inhibitor of JAKs and SFKs, followed by inhibition of Stat3 signaling. Thus, according to in vitro experiments, E738 is a promising new therapeutic agent for human pancreatic cancer treatment by blocking both oncogenic pathways simultaneously.

----------------------------------------------------

[311]

TÍTULO / TITLE:  - Epithelial-Mesenchymal Transition Markers and HER3 Expression Are Predictors of Elisidepsin Treatment Response in Breast and Pancreatic Cancer Cell Lines.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e53645. doi: 10.1371/journal.pone.0053645. Epub 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053645

AUTORES / AUTHORS:  - Teixido C; Mares R; Aracil M; Ramon Y Cajal S; Hernandez-Losa J

INSTITUCIÓN / INSTITUTION:  - Molecular Pathology Group, Vall d’Hebron Research Institute, Universidad Autonoma of Barcelona, Barcelona, España.

RESUMEN / SUMMARY:  - Elisidepsin (elisidepsin trifluoroacetate, Irvalec®, PM02734) is a new synthetic depsipeptide, a result of the PharmaMar Development Program that seeks  synthetic products of marine origin-derived compounds. Elisidepsin is a drug with antiproliferative activity in a wide range of tumors. In the present work we studied and characterized the mechanisms associated with sensitivity and resistance to elisidepsin treatment in a broad panel of tumor cell lines from breast and pancreas carcinomas, focusing on different factors involved in epithelial-mesenchymal transition (EMT) and the use of HER family receptors in predicting the in vitro drug response. Interestingly, we observed that the basal  protein expression levels of EMT markers show a significant correlation with cell viability in response to elisidepsin treatment in a panel of 12 different breast  and pancreatic cancer cell lines. In addition, we generated three elisidepsin treatment-resistant cell lines (MCF-7, HPAC and AsPC-1) and analyzed the pattern  of expression of different EMT markers in these cells, confirming that acquired resistance to elisidepsin is associated with a switch to the EMT state. Furthermore, a direct correlation between basal HER3 expression and sensitivity to elisidepsin was observed; moreover, modulation of HER3 expression levels in different cancer cell lines alter their sensitivities to the drug, making them more resistant when HER3 expression is downregulated by a HER3-specific short hairpin RNA and more sensitive when the receptor is overexpressed. These results  show that HER3 expression is an important marker of sensitivity to elisidepsin treatment.

----------------------------------------------------

[312]

TÍTULO / TITLE:  - Melatonin inhibits the expression of vascular endothelial growth factor in pancreatic cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2012 Dec;24(4):310-6. doi: 10.3978/j.issn.1000-9604.2012.09.03.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.1000-9604.2012.09.03

AUTORES / AUTHORS:  - Lv D; Cui PL; Yao SW; Xu YQ; Yang ZX

INSTITUCIÓN / INSTITUTION:  - Gastroenterology Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.

RESUMEN / SUMMARY:  - OBJECTIVE: To investigate the effects of melatonin on cellular proliferation and  endogenous vascular endothelial growth factor (VEGF) expression in pancreatic carcinoma cells (PANC-1). METHODS: PANC-1 cells were cultured for this study. The secreted VEGF concentration in the culture medium was determined using ELISA method, VEGF production in the tumor cells was detected by immunocytochemistry, and VEGF mRNA expression was determined by RT-PCR. RESULTS: Higher melatonin concentrations significantly inhibited cellular proliferation, with 1 mmol/L concentration exhibiting the highest inhibitory effect (P<0.01). VEGF concentrations in the cell culture supernatants and intra-cellules were all significantly reduced after melatonin (1 mmol/L) incubation (P<0.05). VEGF mRNA expression decreased markedly in a time-dependent manner during the observation period (P<0.05). CONCLUSIONS: High melatonin concentrations markedly inhibited the proliferation of pancreatic carcinoma cells. The endogenous VEGF expression was also suppressed by melatonin incubation.

----------------------------------------------------

[313]

TÍTULO / TITLE:  - Exposure to bisphenol A induces dysfunction of insulin secretion and apoptosis through the damage of mitochondria in rat insulinoma (INS-1) cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Death Dis. 2013 Jan 17;4:e460. doi: 10.1038/cddis.2012.206.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2012.206

AUTORES / AUTHORS:  - Lin Y; Sun X; Qiu L; Wei J; Huang Q; Fang C; Ye T; Kang M; Shen H; Dong S

INSTITUCIÓN / INSTITUTION:  - Key Lab of Urban Environment and Health, Department of Environmental and Molecular Toxicology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.

RESUMEN / SUMMARY:  - Bisphenol A (BPA) is widely used in plastic products, through which humans are exposed to it. Accumulating evidence suggests that BPA exposure is associated with beta-cell dysfunction. Mitochondrial defects can cause impairment and failure of beta cells, but there is little information about the effects of BPA on the mitochondrial function of beta cells. In this study, we assessed the role  of mitochondria-mediated mechanisms underlying BPA-induced beta-cell dysfunction  and resulting beta-cell apoptosis. INS-1 cells were cultured with 0, 0.0020, 0.020, 0.20, or 2.0 muM BPA. Cell viability, glucose-stimulated insulin secretion (GSIS), and mitochondrial function were examined. The mitochondrial apoptotic pathway was also analyzed at molecular level. We found that BPA suppressed cell viability and disturbed GSIS in a dose-dependent manner. Positive Annexin- propidium iodide (PI) staining and altered expression of Bcl-2 family members and caspases in INS-1 cells indicated that the cells progressively became apoptotic after BPA exposure. Additionally, BPA-induced apoptosis was associated with mitochondrial defects in beta cells, as evidenced by depletion of ATP, release of cytochrome c, loss of mitochondrial mass and membrane potential, and alterations  in expression of genes involved in mitochondrial function and metabolism. Taken together, these findings provide strong evidence that BPA triggers INS-1 cells dysfunction and apoptosis may be meditated via the mitochondrial pathway.

----------------------------------------------------

[314]

TÍTULO / TITLE:  - Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995-2012) in South China.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Endocr Disord. 2012 Nov 29;12:30. doi: 10.1186/1472-6823-12-30.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1472-6823-12-30

AUTORES / AUTHORS:  - Wang YH; Lin Y; Xue L; Wang JH; Chen MH; Chen J

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, People’s Republic of China. chenminhu@vip.163.com.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine tumors accounting for 65-75% of neuroendocrine neoplasms (NENs). Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China. METHODS: Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively. RESULTS: Pancreas was found the most common site of involvement (34.8%). 149 patients (83.7%) presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%); carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA) and synaptophysin (Syn) immunhistochemically were 69.1% and  90.2%, respectively. 87 patients (51.5%) had G1 tumors, 31(18.3%) G2 tumors and 51 (30.2%) G3 tumors. Neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC)  and mixed adenoendocrine carcinoma (MANEC) were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4%) patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors. CONCLUSIONS: Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological  classification. Multidisciplinary treatments could help improve the outcome.

----------------------------------------------------

[315]

TÍTULO / TITLE:  - MR imaging and MR Cholangiopancreatography of multiple biliary hamartomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Quant Imaging Med Surg. 2012 Jun;2(2):133-4. doi: 10.3978/j.issn.2223-4292.2012.03.01.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2223-4292.2012.03.01

AUTORES / AUTHORS:  - Gong J; Kang W; Xu J

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Shenzhen People’s Hospital, Jinan University Second Clinical Medicine College, Shenzhen 518020, China.

RESUMEN / SUMMARY:  - Multiple biliary hamartomas (MBH), also known as von Meyenberg complexes, are rare benign malformations of the intrahepatic bile ducts. It is thought that MBH  result from ductal plate malformations involving the small interlobular bile ducts. Proliferation of bile ducts’ cuboidal epithelium in fibrous stroma subsequently leads to duct dilation. Macroscopically, MBH appear as well-defined  subcapsular or parenchymal grayish-white nodules less than 0.5 cm in diameter without true capsulation in an abundant fibrous stroma. MR imaging is considered  the best imaging modality for demonstrating MBH. We herein reported MR imaging and MR cholangiopancreatography of a patient with typical MBH appearance. Multiple tiny T1 hypointense and T2 hyperintense lesions of uniform distribution  in the hepatic parenchyma were revealed. At MR cholangiopancreatography, the lesions were also hyperintense. Maximum intense projection (MIP) of MR cholangiopancreatography showed uniformly distributed hyperintense lesions appearing as “starry sky” configuration.

----------------------------------------------------

[316]

TÍTULO / TITLE:  - Prolonged Survival in an Aged Labrador Retriever with a Metastatic Insulinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Am Anim Hosp Assoc. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 5326/JAAHA-MS-5860

AUTORES / AUTHORS:  - Rychel J; Worley DR; Hardy CS; Webb BT

INSTITUCIÓN / INSTITUTION:  - Fort Collins Veterinary Emergency and Rehabilitation Hospital, Fort Collins, CO,  Colorado State University, Fort Collins, CO.

RESUMEN / SUMMARY:  - This case report highlights an unusually prolonged, asymptomatic, disease-free interval in an aged male Labrador retriever that underwent partial pancreatectomy for a functionally active pancreatic insulinoma with histologically confirmed hepatic metastasis. The patient developed pancreatitis and nonseptic suppurative  peritonitis 24 hr after surgical resection of the insulinoma and was managed medically until discharge. Three mo after surgery, the dog was diagnosed with exocrine pancreatic insufficiency (EPI) that was effectively managed with parenteral pancreatic enzymes. Due to normal glucose levels 3 mo postsurgically,  liver samples from the initial surgery were resubmitted for immunohistochemistry. Results confirmed insulinoma metastasis with insulin expression. Ten mo postsurgically, the blood glucose was normal and serum insulin levels were slightly above the upper reference limit. The first hypoglycemic episode was documented 23 mo postoperatively, which was effectively managed with prednisone.  The cause for the prolonged disease remission and survival was unknown, but was possibly a result of pancreatitis and peritonitis, partial spontaneous regression of metastatic lesions, or idiopathic. Despite life-threatening postoperative complications, this patient enjoyed a profoundly longer than expected survival. This case highlights the importance of removing the primary tumor (insulinoma) despite the presence of metastatic disease.

 

----------------------------------------------------

[317]

TÍTULO / TITLE:  - Antitumor effects of rapamycin in pancreatic cancer cells by inducing apoptosis and autophagy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Mol Sci. 2012 Dec 21;14(1):273-85. doi: 10.3390/ijms14010273.

            ●● Enlace al texto completo (gratuito o de pago) 3390/ijms14010273

AUTORES / AUTHORS:  - Dai ZJ; Gao J; Ma XB; Kang HF; Wang BF; Lu WF; Lin S; Wang XJ; Wu WY

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, the Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an 710004, China. dzj0911@126.com.

RESUMEN / SUMMARY:  - Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This  study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechanism involved in  antitumor activities. MTT assays showed that the inhibition of proliferation of PC-2 cells in vitro was in a time- and dose-dependent manner. By using transmission electron microscopy, apoptosis bodies and formation of abundant autophagic vacuoles were observed in PC-2 cells after Rapa treatment. Flow cytometry assays also showed Rapa had a positive effect on apoptosis. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in PC-2 cells was greater in the Rapa treatment group than  in the control group. RT-PCR revealed that the expression levels of p53, Bax and  Beclin 1 were up-regulated in a dose-dependent manner, indicating that Beclin 1 was involved in Rapa induced autophagy and Rapa induced apoptosis as well as p53  up-regulation in PC-2 cells. The results demonstrated that Rapa could effectively inhibit proliferation and induce apoptosis and autophagy in PC-2 cells.

----------------------------------------------------

[318]

TÍTULO / TITLE:  - Mechanistic evaluation of a novel small molecule targeting mitochondria in pancreatic cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54346. doi: 10.1371/journal.pone.0054346. Epub 2013 Jan 21.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054346

AUTORES / AUTHORS:  - Shabaik YH; Millard M; Neamati N

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, United States of America.

RESUMEN / SUMMARY:  - BACKGROUND: Pancreatic cancer is one of the deadliest cancers with a 5-year survival rate of 6%. Therapeutic options are very limited and there is an unmet medical need for safe and efficacious treatments. Cancer cell metabolism and mitochondria provide unexplored targets for this disease. We recently identified  a novel class of triphenylphosphonium salts, TP compounds, with broad- spectrum anticancer properties. We examined the ability of our prototypical compound TP421- chosen for its fluorescent properties - to inhibit the growth of pancreatic cancer cells and further investigated the molecular mechanisms by which it exerts its anticancer effects. METHODOLOGY/PRINCIPAL FINDINGS: TP421 exhibited sub-micromolar IC(50) values in all the pancreatic cancer cell lines tested using MTT and colony formation assays. TP421 localized predominantly to mitochondria and induced G(0)/G(1) arrest, ROS accumulation, and activation of several stress-regulated kinases. Caspase and PARP-1 cleavage were observed indicating an apoptotic response while LC3B-II and p62 were accumulated indicating inhibition of autophagy. Furthermore, TP421 induced de-phosphorylation of key signaling molecules involved in FAK mediated adhesion that correlated with inhibition of cell migration. CONCLUSIONS/SIGNIFICANCE: TP421 is a representative compound of a new promising class of mitochondrial-targeted agents useful for pancreatic cancer treatment. Because of their unique mechanism of action and efficacy further development is warranted.

----------------------------------------------------

[319]

TÍTULO / TITLE:  - Pancreatic neuroendocrine tumors: biology, diagnosis, and treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer. 2012 Dec 14. doi: 10.5732/cjc.012.10295.

            ●● Enlace al texto completo (gratuito o de pago) 5732/cjc.012.10295

AUTORES / AUTHORS:  - Ro C; Chai W; E Yu V; Yu R

INSTITUCIÓN / INSTITUTION:  - Cedars-Sinai Medical Center, Los Angeles, California 90048, USA run.yu@cshs.org.

RESUMEN / SUMMARY:  - Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in  the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are understood to some degree while the molecular  pathogenesis of PNETs is still unclear. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is not readily predictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally portend less favorable prognosis. Endocrine testing, imaging, and histological evidence are needed for accurate diagnosis of PNETs. An “aggressive” treatment approach with 4 components: surgery, locoregional therapy, systemic therapy, and complication control, has becomes a trend in academic centers throughout the world. The optimal use of the multiple modalities of systemic therapy is still being developed; efficacy, safety, availability, and cost should be considered when treating a specific patient. Clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including a novel Mahvash disease, are summarized.

----------------------------------------------------

[320]

TÍTULO / TITLE:  - Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Death Dis. 2012 Dec 6;3:e441. doi: 10.1038/cddis.2012.181.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2012.181

AUTORES / AUTHORS:  - Fokas E; Prevo R; Pollard JR; Reaper PM; Charlton PA; Cornelissen B; Vallis KA; Hammond EM; Olcina MM; Gillies McKenna W; Muschel RJ; Brunner TB

INSTITUCIÓN / INSTITUTION:  - Gray Institute for Radiation Oncology and Biology, Oxford University, Oxford, UK.

RESUMEN / SUMMARY:  - Combined radiochemotherapy is the currently used therapy for locally advanced pancreatic ductal adenocarcinoma (PDAC), but normal tissue toxicity limits its application. Here we test the hypothesis that inhibition of ATR (ATM-Rad3-related) could increase the sensitivity of the cancer cells to radiation or chemotherapy without affecting normal cells. We tested VE-822, an ATR inhibitor, for in vitro and in vivo radiosensitization. Chk1 phosphorylation  was used to indicate ATR activity, gammaH2AX and 53BP1 foci as evidence of DNA damage and Rad51 foci for homologous recombination activity. Sensitivity to radiation (XRT) and gemcitabine was measured with clonogenic assays in vitro and  tumor growth delay in vivo. Murine intestinal damage was evaluated after abdominal XRT. VE-822 inhibited ATR in vitro and in vivo. VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. VE-822 decreased survival of pancreatic cancer cells but not normal cells in response to XRT or gemcitabine. VE-822 markedly prolonged growth delay of pancreatic cancer xenografts after XRT and gemcitabine-based chemoradiation without augmenting normal cell or tissue toxicity. These findings support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC.

----------------------------------------------------

[321]

TÍTULO / TITLE:  - Cystic “feminine” pancreatic neoplasms in men. Do any clinical alterations correlate with these uncommon entities?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Surg. 2012 Dec 27. pii: S1743-9191(12)00855-2. doi: 10.1016/j.ijsu.2012.12.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijsu.2012.12.008

AUTORES / AUTHORS:  - Regi P; Salvia R; Cena C; Girelli R; Frigerio I; Bassi C

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, HPB Unit, Casa di Cura Dott. Pederzoli, Peschiera Del Garda, Verona, Italy. Electronic address: paoloregi@tiscali.it.

RESUMEN / SUMMARY:  - INTRODUCTION: Mucinous cystic neoplasm (MCN) and solid pseudopapillary neoplasm (SPN) of the pancreas are uncommon hormone-related pancreatic tumors (HRPTs) with a clear predominance in young women. This trial aims to investigate the possible  association between HRPTs development in males and phenotypic and sex hormone alterations. METHODS: We performed a retrospective analysis of our database between February 1990 and February 2012. Risk factors for sexual dysfunction were considered exclusion criteria. We investigated secondary sexual characteristics development, sex hormone level and overall sexual dysfunction degree according with the International Index of Erectile Function Questionnaire (IIEF). RESULTS:  We initially identified 25 patients [(MCN: n = 16 (64%); SPN: n = 9 (36%)]. At follow-up, 5 patients were lost, 8 resulted dead and 3 were excluded according to exclusion criteria. We finally enrolled 9 patients (MCN: n = 5; SPN: n = 4). Puberty occurred within physiological age for 7 patients, whereas it was delayed  in 2 cases. Three patients revealed mild to moderate sexual dysfunction, along with low testosterone level in two cases. One patient presented hormonal alteration with a normal IIEF score. DISCUSSION: In this study, the first in literature with similar aim, hormonal and/or sexual dysfunction was present in 4  out 9 patients affected by HRPT. The rarity of these lesions makes further trials to be needed for reliable conclusions.

----------------------------------------------------

[322]

TÍTULO / TITLE:  - Spontaneous choledochal cyst rupture in pregnancy with concomitant chronic pancreatitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Indian J Gastroenterol. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12664-012-0286-x

AUTORES / AUTHORS:  - Pal S; Simon EG; Koshy AK; Ramakrishna BS; Raju RS; Vyas FL; Joseph P; Sitaram V; Eapen A

INSTITUCIÓN / INSTITUTION:  - Department of Gastrointestinal Sciences, Christian Medical College, Vellore, 632  004, Tamil Nadu, India, drsandippall@gmail.com.

RESUMEN / SUMMARY:  - Choledochal cysts are rare cystic transformations of the biliary tree that are increasingly diagnosed in adult patients. We report here a case of spontaneous rupture of a choledochal cyst in a pregnant young lady with chronic pancreatitis.

 

----------------------------------------------------

[323]

TÍTULO / TITLE:  - Pathogenesis of Metastatic Calcification and Acute Pancreatitis in Adult T-Cell Leukemia under Hypercalcemic State.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Leuk Res Treatment. 2012;2012:128617. doi: 10.1155/2012/128617. Epub 2011 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/128617

AUTORES / AUTHORS:  - Senba M; Kawai K; Mori N

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.

RESUMEN / SUMMARY:  - Human T-cell leukemia virus type-1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL). Hypercalcemia is common in patients with ATL. These patients rarely develop metastatic calcification and acute pancreatitis. The underlying pathogenesis of this condition is osteoclast hyperactivity with associated overproduction of parathyroid hormone-related protein, which results in hypercalcemia in association with bone demineralization. The discovery of the  osteoclast differentiation factor receptor activator of nuclear factor-kappaB ligand (RANKL), its receptor RANK, and its decoy receptor osteoprotegerin (OPG),  enhanced our understanding of the mechanisms of ATL-associated hypercalcemia. Macrophage inflammatory protein-1-alpha, tumor necrosis factor-alpha, interleukin-1, and interleukin-6 are important molecules that enhance the migration and differentiation of osteoclasts and the associated enhanced production of RANKL for osteoblast formation. In this paper, we focus on metastatic calcification and acute pancreatitis in ATL, highlighting recent advances in the understanding of the molecular role of the RANKL/RANK/OPG system  including its interaction with various cytokines and calciotropic hormones in the regulation of osteoclastogenesis for bone resorption in hypercalcemic ATL patients.

----------------------------------------------------

[324]

TÍTULO / TITLE:  - Treatment of pancreatic cancer in a nude mouse model using high-intensity focused ultrasound.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Ther Med. 2013 Jan;5(1):39-44. Epub 2012 Oct 10.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.744

AUTORES / AUTHORS:  - Jiang L; Hu B; Guo Q; Chen L

INSTITUCIÓN / INSTITUTION:  - Department of Ultrasonography, Shanghai Jiaotong University Affiliated No. 6 Hospital, Shanghai 200233, P.R. China.

RESUMEN / SUMMARY:  - The purpose of this study was to determine whether high-intensity focused ultrasound (HIFU) is an effective treatment for pancreatic cancer in an athymic nude mouse model. Female athymic nude mice (n=44) were inoculated subcutaneously  with 5-7x10(6) SW1990 human pancreatic cancer cells. Thirty-six animals developed tumours and were randomly divided into three groups: HIFU (n=18), sham treatment  (n=9) and control (n=9). The sonographic appearance of the tumours during therapy was recorded. After therapy, the tumours were examined transcutaneously by ultrasound every 4 days for 4 weeks. Tissue samples were taken from the treatment sites and histopathologically examined by light or electron microscopy. Two weeks after HIFU treatment, a 100% reduction in tumour volume was observed in all animals in the HIFU group, whereas tumours in the sham-treated and control groups continued to grow. Pathological examination of HIFU-treated tumour tissue samples showed complete coagulation necrosis in the tumour. Our results indicate that HIFU appears to be an effective therapy for pancreatic tumours in an athymic nude mouse model. Thus, the treatment may hold promise for the clinical treatment of late-stage and recurrent pancreatic cancer.

----------------------------------------------------

[325]

TÍTULO / TITLE:  - Balanced Tiam1-rac1 and RhoA Drives Proliferation and Invasion of Pancreatic Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer Res. 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0632

AUTORES / AUTHORS:  - Guo X; Wang M; Jiang J; Xie C; Peng F; Li X; Tian R; Qin R

INSTITUCIÓN / INSTITUTION:  - Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

RESUMEN / SUMMARY:  - Tiam1 is a rac1 specific guanine nucleotide exchange factor and Tiam1-rac1 is involved in a number of cellular processes. Rac1 and RhoA act as molecular switches that cycle between GTP- and GDP-bound states to balance the activities of rac1 and RhoA. The down-regulation of rac1 activity leads to up-regulation of  RhoA activity, which promotes invasion and migration of pancreatic cancers cells. At present, however, the role of Tiam1-rac1 and RhoA in pancreatic cancers is not fully understood. We found that Tiam1 was up-regulated in pancreatic cancers and  was significantly expressed in tumors without lymph node involvement or distant metastasis compared with cancers where there was involvement. Although Tiam1-rac1 signaling promoted pancreatic cancer cell proliferation and tumor growth via the  Wnt signaling pathway in vitro and in vivo, inhibiting Tiam1-rac1 signaling did not prolong the overall survival time in vivo. This provided evidence that there  was a balance between rac1 and RhoA activities in pancreatic cancers. Furthermore, only the combined inhibition of Tiam1-rac1 and RhoA had a beneficial effect on the growth of pancreatic cancers in vivo. Taken together, these results suggest that the progression of pancreatic tumors is partially controlled by the  balance between Tiam1-rac1 and RhoA.

----------------------------------------------------

[326]

TÍTULO / TITLE:  - Novel molecular targets for the treatment of gastroenteropancreatic endocrine tumors: answers and unsolved problems.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Mol Sci. 2012 Dec 20;14(1):30-45. doi: 10.3390/ijms14010030.

            ●● Enlace al texto completo (gratuito o de pago) 3390/ijms14010030

AUTORES / AUTHORS:  - Capurso G; Fendrich V; Rinzivillo M; Panzuto F; Bartsch DK; Delle Fave G

INSTITUCIÓN / INSTITUTION:  - Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome at S. Andrea Hospital, Via di Grottarossa 1035, 00189 Rome, Italy. gianfranco.dellefave@uniroma1.it.

RESUMEN / SUMMARY:  - As more knowledge on molecular alterations favoring carcinogenesis and spreading  of gastroenteropancreatic endocrine tumors has become available, a number of targeted agents interfering with key growth and angiogenic pathways have been explored in preclinical and clinical studies. The mTOR inhibitor Everolimus, and  the multi-target antiangiogenetic agent Sunitinib, have been shown to be effective and thus have been approved by the FDA for treatment of pancreatic endocrine tumors. However, there is little data on the primary resistance to targeted agents on these tumors. The goals of the present review are to elucidate the possible advantage of combined treatments in overcoming induced resistances,  and to identify biomarkers able to predict clinical efficacy. Moreover, the role  of interesting targets for which a strong biological rationale exists, and specific inhibitors are available, such as the Src Family Kinases and the Hedgehog Pathway, are discussed. There is now need for more preclinical studies on cell lines and animal models to provide a stronger preclinical background in this field, as well as clinical trials specifically comparing one targeted therapy with another or combining different targeted agents.

----------------------------------------------------

[327]

TÍTULO / TITLE:  - Is preoperative diagnosis possible? A clinical and radiological review of lymphoepithelial cysts of the pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JOP. 2013 Jan 10;14(1):15-20. doi: 10.6092/1590-8577/1198.

AUTORES / AUTHORS:  - Osiro S; Rodriguez JR; Tiwari KJ; Rodriguez II; Mathenge N; Tubbs RS; Loukas M

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Woodhull Medical and Mental Health Center. Brooklyn, NY,  USA. berilonson@gmail.com.

RESUMEN / SUMMARY:  - Lymphoepithelial cysts of the pancreas are rare lesions found mainly in middle-aged men. They are usually benign and have no clear natural history except one study linking their occurrence with HIV infection. Nevertheless, they often cause enormous psychological stress to patients as they tend to mimic pancreatic  neoplasms which are known to carry poor prognosis. The authors have therefore assessed the published literature from PubMed in order to determine whether lymphoepithelial cysts can be diagnosed preoperatively using novel imaging techniques. Based on our findings, it is evident that three-dimensional computed  tomography scans, in-phase and out-of phase magnetic resonance imaging studies, and endosonography have enabled better characterization of pancreatic lymphoepithelial cysts than a decade ago. Endoscopic ultrasound-guided fine needle aspiration has also added considerably to the promise of preoperative diagnosis. Thus, the authors can affirm that despite surgical excision of the cyst with pathological examination being the gold standard for diagnosis, it is possible that a combination of the modern imaging techniques and/or minimally-invasive approach can enable patients avoid unnecessary surgery in the  future.

----------------------------------------------------

[328]

TÍTULO / TITLE:  - Ectopic mediastinal parathyroid carcinoma presenting as acute pancreatitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Chin Med Assoc. 2013 Feb;76(2):108-11. doi: 10.1016/j.jcma.2011.10.015. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jcma.2011.10.015

AUTORES / AUTHORS:  - Tseng CW; Lin SZ; Sun CH; Chen CC; Yang AH; Chang FY; Lin HC; Lee SD

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology, Department of Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan, ROC; College of Medicine, Tzu Chi University, Hualien, Taiwan, ROC; Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.

RESUMEN / SUMMARY:  - Parathyroid carcinoma is a rare cause of hyperparathyroidism, accounting for fewer than 1% of cases. The incidence of acute pancreatitis in patients with hyperparathyroidism was reported to be only 1.5%. We report a very rare case of ectopic mediastinal parathyroid carcinoma presenting as acute pancreatitis. A 72-year-old man presented with acute pancreatitis and hypercalcemia. During the work-up for hypercalcemia, a mediastinal parathyroid tumor was identified by (99m)Tc-sestamibi scintigraphy and magnetic resonance imaging. The tumor was completely removed via a lower cervical collar incision. The histopathology revealed parathyroid carcinoma. There was no tumor recurrence or abdominal symptoms at 3-year follow-up.

 

----------------------------------------------------

[329]

TÍTULO / TITLE:  - Parameter Identifiability and Sensitivity Analysis Predict Targets for Enhancement of STAT1 Activity in Pancreatic Cancer and Stellate Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS Comput Biol. 2012 Dec;8(12):e1002815. doi: 10.1371/journal.pcbi.1002815. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pcbi.1002815

AUTORES / AUTHORS:  - Rateitschak K; Winter F; Lange F; Jaster R; Wolkenhauer O

INSTITUCIÓN / INSTITUTION:  - Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany.

RESUMEN / SUMMARY:  - The present work exemplifies how parameter identifiability analysis can be used to gain insights into differences in experimental systems and how uncertainty in  parameter estimates can be handled. The case study, presented here, investigates  interferon-gamma (IFNgamma) induced STAT1 signalling in two cell types that play  a key role in pancreatic cancer development: pancreatic stellate and cancer cells. IFNgamma inhibits the growth for both types of cells and may be prototypic of agents that simultaneously hit cancer and stroma cells. We combined time-course experiments with mathematical modelling to focus on the common situation in which variations between profiles of experimental time series, from  different cell types, are observed. To understand how biochemical reactions are causing the observed variations, we performed a parameter identifiability analysis. We successfully identified reactions that differ in pancreatic stellate cells and cancer cells, by comparing confidence intervals of parameter value estimates and the variability of model trajectories. Our analysis shows that useful information can also be obtained from nonidentifiable parameters. For the  prediction of potential therapeutic targets we studied the consequences of uncertainty in the values of identifiable and nonidentifiable parameters. Interestingly, the sensitivity of model variables is robust against parameter variations and against differences between IFNgamma induced STAT1 signalling in pancreatic stellate and cancer cells. This provides the basis for a prediction of therapeutic targets that are valid for both cell types.

----------------------------------------------------

[330]

TÍTULO / TITLE:  - Pancreatic extragastrointestinal stromal tumors, interstitial cajal like cells, and telocytes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JOP. 2013 Jan 10;14(1):1-14. doi: 10.6092/1590-8577/1293.

AUTORES / AUTHORS:  - Padhi S; Sarangi R; Mallick S

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Pondicherry Institute of Medical Sciences. Ganapathychettykulam, Kalapet, Puducherry, India. somanath.padhi@gmail.com.

RESUMEN / SUMMARY:  - CONTEXT: The discovery and subsequent ultrastructural characterization of the interstitial Cajal like cells (now called telocytes) in virtually every anatomic  sites of the human body, by Laurentiu M Popescu and co-workers, have dramatically improved the understanding the function of these cells and pathogenesis of extragastrointestinal stromal tumors (EGIST). Pancreatic extragastrointestinal stromal tumors (pEGIST), phenotypically similar to pancreatic interstitial Cajal  like cells, are extremely rare with an unpredictable biological behavior. OBJECTIVE: To review the clinicopathological, radiological, immunohistochemical,  and therapeutic outcome data of all reported cases of pEGIST, and highlight the developments in the field of pancreatic interstitial Cajal like cells/telocytes.  METHODS: A systematic review of English literature (January 2000 to July 2012) was done by using the search engine of PubMed, PubMed Central, Google Scholar, and the Directory of Open Access Journals. RESULTS: There have been 19 reported cases of pEGIST during the last decade, over an age range of 31 to 84 years (mean: 56 years) with equal gender predilection ((male:female ratio: 9:10). Preoperative radiological characteristics have been mostly nondiagnostic though these were used, in some, for tissue diagnosis. Majority of pEGIST were localized to pancreatic head (8/19, 42.1%), and 15 of 19 patients (78.9%) were symptomatic  at first presentation. The mean size ranged from 2.5 to 35cm (mean: 14 cm). Histomorphological features were that of predominantly spindle cell tumor which consistently expressed c-KIT/CD117 and CD34 by immunohistochemistry, making these two as the most sensitive markers at this site. RESULTS: from studies involving discovery on gastrointestinal stromal tumor 1 (DOG-1), the most specific biomarker of GIST/EGIST, has been inconclusive and this was found to be positive  in one case only. Neoadjuvant chemotherapy with imatinib mesylate and sunitinib were used in few cases, and genetic analysis of c-KIT proto-oncogene was done in  two. By univariate analysis, none of the clinicopathological parameters, except surgical resection with microscopic free margin (R0 resection) (P&lt;0.05), were  found to be an important indicators of outcome. CONCLUSION: The biological behavior of pEGIST, at present, seems unpredictable which requires indefinite period of follow-up. Large number of such cases with genetic analysis supplemented with immunohistochemistry studies will hopefully throw more light in these tumors.

----------------------------------------------------

[331]

TÍTULO / TITLE:  - Neurotransmitter substance P mediates pancreatic cancer perineural invasion via NK-1R in cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer Res. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0609

AUTORES / AUTHORS:  - Li X; Ma G; Ma Q; Li W; Liu J; Han L; Duan W; Xu Q; Liu H; Wang Z; Sun Q; Wang F; Wu E

INSTITUCIÓN / INSTITUTION:  - First Affiliated Hospital of Medical College, Xi’an Jiaotong University.

RESUMEN / SUMMARY:  - Pancreatic cancer significantly affects the quality of life due to the severe abdominal pain. However, the underlying mechanism is not clear. This study aimed  to determine the relationship between SP and pancreatic cancer perineural invasion (PNI) as well as mechanism of SP mediating pancreatic cancer PNI which cause pain in patients with pancreatic cancer. Human pancreatic cancer cells and  newborn dorsal root ganglions (DRGs) were used to determine the expression of SP  or NK-1R in pancreatic cancer cells and DRGs cells by QT-PCR and Western blotting. The effects of SP on pancreatic cancer cell proliferation and invasion  were analyzed using MTT assay and Transwell matrigel invasion assay, respectively. Alterations in the neurotropism of pancreatic cancer cells were assessed by co-culture system which mimics the interaction of tumor/neuron in vivo. SP is not only widely distributed in the neurite outgrowth from newborn DRGs but also expressed in MIA PaCa-2 and BxPC-3 cells. NK-1R is found to be overexpressed in the pancreatic cancer cell lines examined. SP induces cancer cell proliferation and invasion as well as the expression of MMP-2 in pancreatic  cancer cells; and NK-1R antagonists inhibit these effects. Furthermore, SP promotes neurite outgrowth and the migration of pancreatic cancer cell cluster to the DRGs, which is blocked by NK-1R antagonists in the co-culture model. Our results suggest that SP plays an important role in the development of pancreatic  cancer metastasis and PNI; and blocking the SP/NK-1R signaling system is a novel  strategy for the treatment of pancreatic cancer.

----------------------------------------------------

[332]

TÍTULO / TITLE:  - Glycolysis in Panc-1 human pancreatic cancer cells is inhibited by everolimus.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Ther Med. 2013 Jan;5(1):338-342. Epub 2012 Nov 1.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.787

AUTORES / AUTHORS:  - Liu L; Gong L; Zhang Y; Li N

INSTITUCIÓN / INSTITUTION:  - National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

RESUMEN / SUMMARY:  - The aim of this study was to evaluate the effects and molecular mechanisms of everolimus on Panc-1 human pancreatic cancer cells. Panc-1 human pancreatic cancer cells were treated with everolimus (10 mug/ml) at selected time points (6, 12 and 24 h). Cell proliferation and apoptosis were evaluated by MTT and flow cytometric analyses. The glycolytic activity was determined by measuring the activity of the key enzyme lactate dehydrogenase (LDH) and lactate production. The activity of mammalian target of rapamycin (mTOR) signaling was measured by western blotting. The expression of genes, including hexokinase 2 (HK2) and microRNA-143 (miR-143), was evaluated by real-time polymerase chain reaction (PCR). The administration of everolimus time-dependently inhibited proliferation  and glycolysis and induced apoptosis in the Panc-1 human pancreatic cancer cells. As the time of treatment with everolimus increased, the mTOR signaling activity decreased, indicated by lower phosphorylation levels of S6 kinase; however, the phosphorylation levels of mTOR barely changed. Moreover, our data showed an everolimus-induced increase in miR-143 and decrease in HK2 in Panc-1 cells in a time-dependent manner. In conclusion, the current study indicates a novel role of everolimus in its antitumor effect as an inhibitor of glycolysis in Panc-1 human  pancreatic cancer cells. Furthermore, our data highlights the significance of exploring the mechanisms of everolimus and miR-143 in malignant tumors.

----------------------------------------------------

[333]

TÍTULO / TITLE:  - Naringenin Decreases Invasiveness and Metastasis by Inhibiting TGF-beta-Induced Epithelial to Mesenchymal Transition in Pancreatic Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e50956. doi: 10.1371/journal.pone.0050956. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0050956

AUTORES / AUTHORS:  - Lou C; Zhang F; Yang M; Zhao J; Zeng W; Fang X; Zhang Y; Zhang C; Liang W

INSTITUCIÓN / INSTITUTION:  - Department of Gastrointestinal Medical Oncology, The Affiliated Third Hospital of Harbin Medical University, Institute of Prevention and Treatment of Cancer of Heilongjiang Province, Harbin, People’s Republic of China ; Protein & Peptide Pharmaceutical Laboratory, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People’s Republic of China.

RESUMEN / SUMMARY:  - Epithelial to mesenchymal transition (EMT) promotes cellular motility, invasiveness and metastasis during embryonic development and tumorigenesis. Transforming growth factor-beta (TGF-beta) signaling pathway is a key regulator of EMT. A lot of evidences suggest that this process is Smad3-dependent. Herein we showed that exposure of aspc-1 and panc-1 pancreatic cancer cells to TGF-beta1 resulted in characteristic morphological alterations of EMT, and enhancement of cell motility and gemcitabine (Gem) resistance along with an up-regulation of EMT markers genes such as vimentin, N-cadherin, MMP2 and MMP9. Naringenin (Nar) down-regulated EMT markers expression in both mRNA and protein levels by inhibiting TGF-beta1/Smad3 signal pathway in the pancreatic cancer cells. Consequently, Nar suppressed the cells migration and invasion and reversed their  resistance to Gem.

----------------------------------------------------

[334]

TÍTULO / TITLE:  - Garcinol sensitizes human pancreatic adenocarcinoma cells to gemcitabine in association with microRNA signatures.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Nutr Food Res. 2013 Feb;57(2):235-48. doi: 10.1002/mnfr.201200297. Epub 2013  Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1002/mnfr.201200297

AUTORES / AUTHORS:  - Parasramka MA; Ali S; Banerjee S; Deryavoush T; Sarkar FH; Gupta S

INSTITUCIÓN / INSTITUTION:  - Department of Nutrition and Food Science, School of Liberal Arts and Science, Wayne State University, Detroit, MI, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Alterations in microRNA (miRNA/miR) genes are of biological importance in the pathophysiology of cancers, including pancreatic cancer (PaCa). Although growing evidence supports the role of miRNA in cancer, their response to dietary phytochemicals is less known. Previously, we showed that garcinol induces PaCa cell growth arrest and apoptosis in vitro. The present study, discusses chemo-sensitization by garcinol in synergism with first-line PaCa drug, gemcitabine. The miRNA expression profile of gemcitabine-resistant Panc-1 cells treated with garcinol and/or gemcitabine was also evaluated. METHODS AND RESULTS: Garcinol synergizes with gemcitabine to inhibit cell proliferation and induce apoptosis in PaCa cells with significant modulation of key cancer regulators including PARP, VEGF, MMPs, ILs, caspases, and NF-kappaB. In addition, biostatistical analyses, quantitative reverse transcription PCR data, and in silico modeling using TargetScan5, PicTar, and DNA intelligent analysis, microT-V.B4 database showed that these two agents modulated a number of microRNAs (miR-21, miR-196a, miR-495, miR-605, miR-638, and miR-453) linked to various canonical oncogenic signaling pathways. CONCLUSION: We identified garcinol-specific miRNA biomarkers that sensitize PaCa cells to gemcitabine treatment, thus attenuating the drug-resistance phenotype. These results prompt further interest in garcinol and gemcitabine combination strategy as a drug modality to improve treatment outcome in patients diagnosed with PaCa.

----------------------------------------------------

[335]

TÍTULO / TITLE:  - ADAM15 is involved in MICB shedding and mediates the effects of gemcitabine on MICB shedding in PANC-1 pancreatic cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Med Report. 2013 Jan 11. doi: 10.3892/mmr.2013.1272.

            ●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1272

AUTORES / AUTHORS:  - Duan X; Mao X; Sun W

INSTITUCIÓN / INSTITUTION:  - Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, Changsha 410005, P.R. China.

RESUMEN / SUMMARY:  - The aim of this study was to investigate the role of ADAM15 in MHC class I polypeptide-related sequence B (MICB) protein ectodomain shedding and observe whether or not gemcitabine affects MICB shedding from PANC-1 cells. In this study, immunohistochemistry of MICB and ADAM15 were performed on tumor samples obtained from 93 patients with pancreatic ductal adenocarcinoma (PDAC). The expression of MICB and ADAM15 in the PDAC tissues was significantly higher compared with that in the normal tissues of the pancreas. Statistical analysis showed a significant correlation between the expression of MICB and certain classic clinicopathological characteristics (i.e., histological grade and TNM stage). ADAM15 expression was found to correlate with lymph node metastasis and TNM stage. The Spearman’s rank test suggested that the expression of MICB was inversely correlated with that of ADAM15 in PDAC tissues. Knockdown of ADAM15 in  PANC-1 cells clearly upregulated MICB expression on the cellular surface and downregulated soluble MICB (sMICB) levels in the culture supernatants. A non-toxic dose of 0.5 micromol/l gemcitabine suppresses ADAM15 expression leading, at the same time, to an increase in MICB expression and a decrease in sMICB production in PANC-1 cells. The mRNA levels of MICB did not change following PANC-1 exposure to gemcitabine. Further study suggests that the suppressive effect of gemcitabine on MICB shedding in PANC-1 cells is mediated by ADAM15 downregulation. In conclusion, the results of the present study support the hypothesis that ADAM15 is involved in MICB shedding of PANC-1 cells and that  gemcitabine inhibits MICB ectodomain shedding through the suppression of ADAM15.

----------------------------------------------------

[336]

TÍTULO / TITLE:  - Beam angle selection for intensity-modulated radiotherapy (IMRT) treatment of unresectable pancreatic cancer: are noncoplanar beam angles necessary?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Oncol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0998-5

AUTORES / AUTHORS:  - Chang DS; Bartlett GK; Das IJ; Cardenes HR

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, IU Simon Cancer Center, Indiana University School of Medicine, 535 Barnhill Dr., RT 041, Indianapolis, IN, 46202, USA, dschang@iupui.edu.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE: External beam radiation therapy with concurrent chemotherapy (CRT) is widely used for the treatment of unresectable pancreatic cancer. Noncoplanar (NCP) 3D conformal radiotherapy (3DCRT) and coplanar (CP) IMRT have been reported to lower the radiation dose to organs at risk (OARs). The purpose of this article is to examine the utility of noncoplanar beam angles in IMRT for the management of pancreatic cancer. MATERIALS AND METHODS: Sixteen patients who were treated with CRT for unresectable adenocarcinoma of the pancreatic head or neck were re-planned using CP and NCP beams in 3DCRT and IMRT  with the Varian Eclipse treatment planning system. RESULTS: Compared to CP IMRT,  NCP IMRT had similar target coverage with slightly increased maximum point dose,  5,799 versus 5,775 cGy (p = 0.008). NCP IMRT resulted in lower mean kidney dose,  787 versus 1,210 cGy (p < 0.0001) and higher mean liver dose, 1,208 versus 1,061  cGy (p < 0.0001). Also, NCP IMRT resulted in similar mean stomach dose, 1,257 versus 1,248 cGy (p = 0.86) but slightly higher mean small bowel dose, 981 versus 866 cGy (p < 0.0001). CONCLUSIONS: The NCP IMRT was able to significantly decrease bilateral kidney dose, but did not improve other dose-volume criteria. The use of NCP beam angles is preferred only in patients with risk factors for treatment-related kidney dysfunction.

----------------------------------------------------

[337]

TÍTULO / TITLE:  - Surgical treatment of multiple spine metastases from gastrinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Evid Based Spine Care J. 2011 Nov;2(4):45-50. doi: 10.1055/s-0031-1274756.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0031-1274756

AUTORES / AUTHORS:  - Crabtree KL; Anderson KK; Haynes NG; Arnold PM

INSTITUCIÓN / INSTITUTION:  - University of Kansas Medical Center, Kansas City, KS, USA.

RESUMEN / SUMMARY:  - Study design: Case report.Clinical question: To report successful surgical therapy for spinal cord compression in a patient with spinal metastases from a pancreatic gastrinoma.Methods: A 43-year-old man presented three times within 4 years with cervical and upper thoracic spinal cord compression because of metastatic gastrinoma. He had two previous spine metastases to the lower thoracic and lumbar spine, a T11 compressive lesion which required a T9L1 fusion, and an L4 lesion that was treated with chemotherapy and stereotactic radiation. The compression was relieved each time by surgery.Results: The patient underwent three surgeries in 4 years: (1) debulking and removal of the rib head on the left at T3, and debulking of the tumor at T3 with hemilaminectomy and spinal cord decompression with internal fixation from T1-T5 using posterolateral instrumented fusion and allograft; (2) anterior C7 corpectomy with placement of a cage from C7-T1 with both anterior and posterior fusion of C2C7; and (3) T1-T3 laminectomy, T1-T3 exploration of wound, revision of hardware, T1-T3 removal of spinal tumor,  and T3 bilateral transpedicular circumferential decompression. The patient is alive and regained the ability to walk 8 years after initial diagnosis, despite the appearance of spinal metastases 1 year after the diagnosis of liver metastases.Conclusion: Surgery for spinal cord compression in patients with metastatic neuroendocrine tumors can be effective in relieving radicular pain, weakness and numbness, and while not curative can greatly improve quality of life.

----------------------------------------------------

[338]

TÍTULO / TITLE:  - Stent patency using competing risk model in unresectable pancreatic cancers inserted with biliary self-expandable metallic stent.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Dig Endosc. 2013 Jan;25(1):67-75. doi: 10.1111/j.1443-1661.2012.01335.x. Epub 2012 Jun 11.

            ●● Enlace al texto completo (gratuito o de pago) 1111/j.1443-1661.2012.01335.x

AUTORES / AUTHORS:  - Eum YO; Kim YT; Lee SH; Park SW; Hwang JH; Yoon WJ; Ryu JK; Yoon YB; Han JK; Yoon CJ; Cho JH; Choi Y

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Internal Medicine, Cheongju St Mary’s Hospital, Cheongju, Korea.

RESUMEN / SUMMARY:  - BACKGROUND AND AIM: Biliary self-expandable metallic stents (SEMS) play an important role in the quality of life and palliative treatment in unresectable pancreatic cancer patients. We aimed to determine the factors affecting the patency of biliary SEMS and the survival in unresectable pancreatic cancer with obstructive jaundice. METHODS: Considering the competing risk and survival, we retrospectively evaluated the patency in 107 unresectable pancreatic cancer patients with obstructive jaundice who were successfully treated with biliary SEMS from January 2000 to April 2010. RESULTS: There were 107 incidents of biliary drainage that were clinically successful and the overall survival period  was a median of 133 days. Stent occlusion before death was observed in 36 (33.6%) of 107 patients. Cumulative stent obstruction rates were4.7%, 16.8%, and 24.4% at 1, 3, and 6 months, respectively. Lower cancer stage (<5 month’s hazard ratio [HR] = 2.327, >5 month’s HR = 0.108) was only associated with the longer patency  of the stents in a multivariable analysis using a Fine and Gray model that considered competing risk. In multivariable analysis, lower cancer stage, uncovered stent and normalized serum bilirubin level were associated with a longer survival period (HR = 2.335, 1.906 and 1.795 respectively, P < 0.05). CONCLUSION: The patency of biliary SEMS in unresectable pancreatic cancers might  be affected by the stage. Lower cancer stage and normalized bilirubin are associated with longer survival.

----------------------------------------------------

[339]

TÍTULO / TITLE:  - CXCR4 expression predicts early liver recurrence and poor survival after resection of pancreatic adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Gastroenterol. 2012 Sep 13;3:e22. doi: 10.1038/ctg.2012.18.

            ●● Enlace al texto completo (gratuito o de pago) 1038/ctg.2012.18

AUTORES / AUTHORS:  - Liao WC; Wang HP; Huang HY; Wu MS; Chiang H; Tien YW; Lin YL; Lin JT

INSTITUCIÓN / INSTITUTION:  - 1] Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan [2] Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.

RESUMEN / SUMMARY:  - OBJECTIVES: Liver metastasis develops in 60% of patients after resection of pancreatic adenocarcinoma (PAC) and carries a dismal prognosis, but factors predictive of liver recurrence are poorly understood. Experimental evidence suggests that liver metastasis of PAC is mediated by CXCL12/CXCR4 signaling and can be inhibited by CXCR4 antagonist. We aimed to verify whether CXCR4 expression predicts early liver recurrence and poor survival after resection, and to explore the usefulness of CXCR4 status for prognosis prediction. METHODS: Ninety-seven consecutive PAC patients undergoing R0 resection were analyzed. CXCR4 expression  was analyzed by immunohistochemistry, and its associations with liver recurrence-free survival and overall survival were analyzed by Kaplan-Meier estimates and multivariable Cox and accelerated failure time regression models. RESULTS: CXCR4-positive patients had a worse prognosis than CXCR4-negative patients, with a shorter liver recurrence-free survival (median: 8.7 vs. 39.7 months; P=0.004) and overall survival (median: 10.2 vs. 22.3 months; P<0.001). Overall survival for CXCR4-positive stage IIa patients was similar to that for stage IIb patients and significantly shorter than that for CXCR4-negative stage IIa patients (median: 9.7 vs. 27.4 months; P=0.002). CXCR4 positivity was significantly associated with liver recurrence (adjusted hazard ratio 2.22, 95% confidence interval (CI) 1.15-4.30; P=0.018) and predicted a 46% (95% CI 9-68%) and 35% (95% CI 7-54%) reduction in liver recurrence-free survival and overall survival, respectively. CONCLUSIONS: Tumor CXCR4 expression independently predicts early liver recurrence and poor overall survival after resection of PAC. CXCR4 status stratifies stage IIa patients into two groups with a striking difference in prognosis.

----------------------------------------------------

[340]

TÍTULO / TITLE:  - Metastatic pancreatic cancer: are we making progress in treatment?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastroenterol Res Pract. 2012;2012:898931. doi: 10.1155/2012/898931. Epub 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/898931

AUTORES / AUTHORS:  - Chiu J; Yau T

INSTITUCIÓN / INSTITUTION:  - University Department of Medicine, Queen Mary Hospital, Hong Kong.

RESUMEN / SUMMARY:  - Development of systemic treatment for advanced pancreatic cancer (APC) has been challenging. After fluorouracil, gemcitabine (GEM) became the treatment of choice based on its benefit of symptom relief. Many cytotoxic agents have been combined  with GEM in search of regimens with improved survival benefit. However, there were only marginal benefits in people with good performance status. Recently, the combination regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) was found to achieve unprecedented survival benefit and has become the preferred option for patients with good clinical conditions. On the other hand, many biological agents have been combined with GEM, but only erlotinib was found to derive statistically significant survival advantage. However, the effect was too small to be appreciated clinically. The effort in development of targeted therapy in APC continues. This paper summarized key findings in the development of chemotherapy and targeted therapy for APC patients and discussed future directions in management.

----------------------------------------------------

[341]

TÍTULO / TITLE:  - Treatment of locally advanced unresectable pancreatic cancer: a 10-year experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Oncol. 2012 Dec;3(4):326-34. doi: 10.3978/j.issn.2078-6891.2012.029.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2078-6891.2012.029

AUTORES / AUTHORS:  - Malik NK; May KS; Chandrasekhar R; Wee W; Flaherty L; Iyer R; Gibbs J; Kuvshinoff B; Wilding G; Warren G; Yang GY

INSTITUCIÓN / INSTITUTION:  - Departments of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California, USA.

RESUMEN / SUMMARY:  - PURPOSE: We retrospectively analyzed the results of patients with locally advanced unresectable pancreatic cancer (LAPC) treated with either chemoradiation (CRT) or chemotherapy alone over the past decade. METHODS AND MATERIALS: Between  December 1998 and October 2009, 116 patients with LAPC were treated at our institution. Eighty-four patients received concurrent chemoradiation [RT (+) group], primarily 5-flourouracil based (70%). Thirty-two patients received chemotherapy alone [RT (-) group], the majority gemcitabine based (78%). Progression-free survival (PFS) and overall survival (OS) were calculated from date of diagnosis to date of first recurrence and to date of death or last follow-up, respectively. Univariate statistical analysis was used to determine significant prognostic factors for overall survival. RESULTS: Median patient age  was 67 years. Sixty patients were female (52%). Median follow-up was 11 months (range, 1.6-59.4 months). The RT (+) group received a median radiation dose of 50.4 Gy, was more likely to present with ECOG 0-1 performance status, and experienced less grade 3-4 toxicity. PFS was 10.9 versus 9.1 months (P=0.748) and median survival was 12.5 versus 9.1 months (P=0.998) for the RT (+) and RT (-) groups respectively (P=0.748). On univariate analysis, patients who experienced grade 3-4 toxicity had worse overall survival than those who did not (P=0.02). CONCLUSIONS: Optimal management for LAPC continues to evolve. Patients who developed treatment-related grade 3-4 toxicity have a poorer prognosis. Survival  rates were not statistically significant between chemotherapy and chemoradiotherapy groups.

----------------------------------------------------

[342]

TÍTULO / TITLE:  - Effects of a Non Thermal Plasma Treatment Alone or in Combination with Gemcitabine in a MIA PaCa2-luc Orthotopic Pancreatic Carcinoma Model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52653. doi: 10.1371/journal.pone.0052653. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052653

AUTORES / AUTHORS:  - Brulle L; Vandamme M; Ries D; Martel E; Robert E; Lerondel S; Trichet V; Richard S; Pouvesle JM; Le Pape A

INSTITUCIÓN / INSTITUTION:  - Centre d’Imagerie du Petit Animal (CIPA) TAAM, UPS44 CNRS, Orleans, France ; Centre de Recherche Biologique (CERB), Baugy, France.

RESUMEN / SUMMARY:  - Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun) was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects  of Plasma Gun alone or in combination with gemcitabine. During a 36 days period,  quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties.

----------------------------------------------------

[343]

TÍTULO / TITLE:  - Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biol Open. 2012 Apr 15;1(4):295-307. Epub 2012 Feb 10.

            ●● Enlace al texto completo (gratuito o de pago) 1242/bio.2012539

AUTORES / AUTHORS:  - Yee NS; Zhou W; Chun SG; Liang IC; Yee RK

INSTITUCIÓN / INSTITUTION:  - Division of Hematology-Oncology, Department of Medicine, Penn State College of Medicine; Penn State Hershey Cancer Institute; Penn State Milton S. Hershey Medical Center; The Pennsylvania State University , Hershey, PA 17033 , USA ; Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department  of Internal Medicine, Carver College of Medicine; Program of Cancer Signaling and Experimental Therapeutics, Holden Comprehensive Cancer Center; The University of  Iowa, Iowa City , IA 52242 , USA.

RESUMEN / SUMMARY:  - Histone deacetylases (HDACs) and RNA polymerase III (POLR3) play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis in zebrafish. We aim to  test the hypothesis that Hdacs and Polr3 cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A) and an inhibitor of Polr3 (ML-60218) synergistically prohibited the expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and ML-60218 produced augmented suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive upregulation of the pro-apoptotic regulator BAX and the cyclin-dependent kinase inhibitor p21(CDKN1A). tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators of exocrine pancreas can be translated into an approach with potential impact on therapeutic response in pancreatic cancer, and  suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity.

----------------------------------------------------

[344]

TÍTULO / TITLE:  - An update on minimally invasive therapies for pancreatic necrosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Rev Gastroenterol Hepatol. 2012 Dec;6(6):745-53. doi: 10.1586/egh.12.48.

            ●● Enlace al texto completo (gratuito o de pago) 1586/egh.12.48

AUTORES / AUTHORS:  - Easler JJ; Zureikat A; Papachristou GI

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh, PA, USA.

RESUMEN / SUMMARY:  - Pancreatic necrosis is a local complication of severe acute pancreatitis associated with multiple organ dysfunction, infection and increased mortality. While surgery is the mainstay for invasive management, studies have demonstrated  that delaying necrosectomy translates to improved patient outcomes. Minimally invasive therapies have been described both for early and late management of necrotic pancreatic collections and fall into three broad categories: endoscopic, radiology assisted percutaneous drainage and laparoscopic or retroperitoneal surgical techniques. Such interventions may serve as temporizing measures delaying necrosectomy, but more importantly, as best demonstrated in recent randomized controlled trials, can serve as alternative approaches resulting in improved patient outcomes. Access to these techniques is based on their availability at expert centers. Minimally invasive therapies have increased in popularity, with a general consensus among experts being that reduced complications and mortality rates are realized by approaches other than open necrosectomy. However, additional well-designed, randomized trials are needed.

----------------------------------------------------

[345]

TÍTULO / TITLE:  - Solid pseudopapillary tumor of pancreas in a male child: A diagnosis by fine needle aspiration cytology.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Fetal Pediatr Pathol. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 3109/15513815.2012.754522

AUTORES / AUTHORS:  - Nasit JG; Jetly D; Shah M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, P.D.U. Govt. Medical College , Rajkot, Gujrat , India.

RESUMEN / SUMMARY:  - Solid pseudopapillary tumor (SPT) is an uncommon pancreatic neoplasm with low malignant potential. It occurs predominantly in young women. It is very rare in males and nonrelated pediatrics. In children, SPT commonly present as abdominal mass and pain. A 10-year-old male presented with progressively growing palpable tumor in upper abdomen. SPT of pancreas is diagnosed on preoperative fine needle  aspiration cytology. This was subsequently confirmed by histopathology and immunohistochemistry. Due to rarity, SPT is not the first option to rule out, especially in children. Preoperative cytological diagnosis of SPT helps in management of this surgically curable neoplasm with good prognosis.

----------------------------------------------------

[346]

TÍTULO / TITLE:  - Pancreatic cyst cytology: Optimization of cancer risk profiling.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Cytopathol. 2013 Jan;121(1):2-3. doi: 10.1002/cncy.21267.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncy.21267

AUTORES / AUTHORS:  - Schmidt CM

INSTITUCIÓN / INSTITUTION:  - Departments of Surgery and Biochemistry/Molecular Biology and Indiana University  Health Pancreatic Cyst and Cancer Early Detection Center.

----------------------------------------------------

[347]

TÍTULO / TITLE:  - Sorafenib inhibits tumor growth and improves survival in a transgenic mouse model of pancreatic islet cell tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - ScientificWorldJournal. 2012;2012:529151. doi: 10.1100/2012/529151. Epub 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1100/2012/529151

AUTORES / AUTHORS:  - Fendrich V; Maschuw K; Rehm J; Buchholz M; Holler JP; Slater EP; Bartsch DK; Waldmann J

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University Hospital Giessen and Marburg, Baldinger Strasse, 35043 Marburg, Germany.

RESUMEN / SUMMARY:  - Background. The purpose of the study was to evaluate Sorafenib (BAY 43-9006) derived receptor tyrosine kinase inhibition on tumor progression in murine islet  cell tumors. Sorafenib is considered to be a potent inhibitor of tumor angiogenesis and neovascularization in various solid tumors. Rip1Tag2 mice were treated in two different groups according to the model of tumor progression: the  early treatment group received vehicle or Sorafenib from 10 to 14 weeks of age and the late treatment group from week 12 until death. Tumor surface, tumor cell  proliferation, and apoptosis were measured in both treatment groups to assess the in vivo effects of Sorafenib. Survival was recorded for the late treatment group. In the early treatment group Sorafenib led to a dramatic decrease in tumor volume compared to the control group. Apoptosis was significantly augmented and cell proliferation was inhibited. As a single therapy Sorafenib significantly improved survival in the late treatment group. Conclusion. Sorafenib may provide a new paradigm for the therapy of islet cell tumors.

----------------------------------------------------

[348]

TÍTULO / TITLE:  - A contemporary analysis of survival for resected pancreatic ductal adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - HPB (Oxford). 2013 Jan;15(1):49-60. doi: 10.1111/j.1477-2574.2012.00571.x. Epub 2012 Sep 24.

            ●● Enlace al texto completo (gratuito o de pago) 1111/j.1477-2574.2012.00571.x

AUTORES / AUTHORS:  - Lewis R; Drebin JA; Callery MP; Fraker D; Kent TS; Gates J; Vollmer CM Jr

INSTITUCIÓN / INSTITUTION:  - Departments of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, 19104, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: Survival after a resected pancreatic ductal adenocarcinoma (PDAC) appears to be improving. Yet, in spite of advancements, prognosis remains disappointing. This study analyses a contemporary experience and identifies features associated with survival. METHODS: Kaplan-Meier analysis was conducted for 424 PDAC resections performed at two institutions (2001-2011). Multivariate analysis was performed to elicit characteristics independently associated with survival. RESULTS: The median, 1-, and 5-year survivals were 21.3 m, 76%, and 23%, with 30/90-day mortalities of 0.7%/1.7%. 76% of patients received adjuvant therapy. Patients with major complications (Clavien Grade IIIb-IV) survived equivalently to patients with no complications (P = 0.33). The median and 5-year  survival for a total pancreatectomy was 32.2 m/49%; for 90 ‘favourable biology’ patients (R0/N0/M0) was 37.3 m/40%; and for IPMN (9% of series) was 21.2 m/46%. Elderly (>75 yo) and nonelderly patients had similar survival. Favorable prognostic features by multivariate analysis include lower POSSUM physiology score, R0 resection, absence of operative transfusion, G1/G2 grade, absence of lymphovascular invasion, T1/T2 stage, smaller tumor size, LN ratio <0.3, and receipt of adjuvant therapy. CONCLUSION: This experience with resected PDAC shows decreasing morbidity and mortality rates along with modestly improving long-term  survival, particularly for certain subgroups of patients. Survival is related to  pathological features, pre-operative physiology, operative results and adjuvant therapy.

----------------------------------------------------

[349]

TÍTULO / TITLE:  - Morphological Analysis and Differentiation of Benign Cystic Neoplasms of the Pancreas Using Computed Tomography and Magnetic Resonance Imaging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Rofo. 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1325551

AUTORES / AUTHORS:  - Grieser C; Heine G; Stelter L; Steffen IG; Rothe JH; Walter TC; Fischer C; Bahra M; Denecke T

INSTITUCIÓN / INSTITUTION:  - Klinik fur Radiologie, Campus Virchow-Klinikum, Charite - Universitatsmedizin Berlin.

RESUMEN / SUMMARY:  - Purpose: To evaluate morphologic characteristics and establish a standardized diagnostic algorithm to differentiate benign cystic pancreatic tumors (CPTs) in non-pancreatitis patients using multidetector computed tomography (CT) and magnetic resonance imaging (MRI).Materials and Methods: Patients with histopathologically proven CPTs who had undergone MRI and/or CT and subsequent tumor resection in our institution were retrospectively identified. Images were analyzed for morphology and enhancement patterns by three independent blinded observers. Preoperative image findings were correlated with histopathological results. Based on the evaluated morphologic parameters, a standardized diagnostic algorithm was designed to help characterize the lesions.Results: A total of 62 consecutive patients with 64 CPTs were identified from the surgical database (21  intraductal papillary mucinous neoplasms; 10 mucinous cystic neoplasms; 12 serous microcystic adenomas; 3 serous oligocystic adenomas; 6 solid pseudopapillary tumors; 12 neuroendocrine neoplasms). The overall averaged accuracy for the 3 observers was 89.9 % for CT and 93.1 % for MRI with increasing overall accuracy in relation to the experience of the observer (88.2 %, 91.5 %, and 93.8 %, respectively). Overall, the generalized kappa value was 0.69 (CT, 0.64; MRI, 0.76); p < 0.001). The accuracy of the standardized diagnostic algorithm was 91.1 %.Conclusion: It is possible to characterize benign CPTs with MRI and CT, while MRI appears to be superior to CT. Diagnostic accuracy depends on the observer’s experience. The standardized algorithm can aid in the differential diagnosis but  still needs to be tested in other patient populations.

----------------------------------------------------

[350]

TÍTULO / TITLE:  - Radiotherapy: MRI underestimates the size of pancreatic adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Clin Oncol. 2013 Jan 22. doi: 10.1038/nrclinonc.2013.7.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrclinonc.2013.7

----------------------------------------------------

[351]

TÍTULO / TITLE:  - Annexin A1, A2, A4 and A5 play important roles in breast cancer, pancreatic cancer and laryngeal carcinoma, alone and/or synergistically.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):107-112. Epub 2012 Oct 9.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.959

AUTORES / AUTHORS:  - Deng S; Wang J; Hou L; Li J; Chen G; Jing B; Zhang X; Yang Z

INSTITUCIÓN / INSTITUTION:  - Department of Anatomy and ; Morphometric Research Laboratory, North Sichuan Medical College;

RESUMEN / SUMMARY:  - Annexins are associated with metastasis and infiltration of cancer cells. Proteomic analysis and immunohistochemical staining were used to understand whether several annexins play important roles in cancer alone and/or synergistically. Seven fresh breast cancer samples with 23 paraffin specimens, three fresh pancreatic samples and five fresh laryngeal carcinoma samples with 25 paraffin specimens were obtained from humans, as well as ten golden hamster pancreatic cancer tissue samples, and they were used to observe differential expression of annexins compared with normal tissues using proteomics and immunohistochemical staining. Annexin A2, A4 and A5 were overexpressed in human breast cancer and laryngeal carcinoma tissues and in golden hamster pancreatic cancer tissue samples, respectively, as shown by proteomics and immunohistochemical staining. In addition, annexin A4 and A5 were expressed in breast cancer tissues, while annexin A1 was not expressed. Annexin A1, A2 and A4  were expressed in human laryngeal carcinoma tissues as shown by immunohistochemical staining. Annexin A1, A2, A4 and A5 played important roles in breast cancer, pancreatic cancer and laryngeal carcinoma, alone and/or synergistically, and they may be targets of therapy for malignant tumors. The choice of which annexins to target should depend on their respective biological behaviors.

----------------------------------------------------

[352]

TÍTULO / TITLE:  - Expression of novel tumor markers of pancreatic adenocarcinomas in intrahepatic cholangiocarcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Onco Targets Ther. 2013;6:19-23. doi: 10.2147/OTT.S39646. Epub 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S39646

AUTORES / AUTHORS:  - Zong M; Jia L; Li L

INSTITUCIÓN / INSTITUTION:  - Zibo Vocational Institute, Zibo, China.

RESUMEN / SUMMARY:  - Intrahepatic cholangiocarcinomas (IHCCs) are morphologically and biologically similar to pancreatic ductal adenocarcinomas (PDACs), so newly identified PDAC-associated genes or proteins could provide clues for screening novel biomarkers for IHCC. In this study, the expression of three novel PDAC tumor markers (T-box transcription factor-4 [TBX4], heat shock protein-60 [HSP60], and  Parkinson protein-7 [DJ-1]) identified in previous proteomic studies in IHCC tumors were immunohistochemically detected. The current study confirmed that three novel pancreatic cancer biomarkers TBX4, HSP60, and DJ-1 were also overexpressed in IHCC tumors, but with a relatively lower expression level than PDAC. No significant association was found between tumor marker expression and the clinicopathological characteristics of IHCC patients except that TBX4 expression correlated with tumor grades. Moreover, DJ-1 was demonstrated to be an independent prognostic factor for these patients. The current findings suggest that DJ-1 might play an important role in the malignant progression of IHCC, and  its exact mechanism during IHCC progression deserves further investigation.

----------------------------------------------------

[353]

TÍTULO / TITLE:  - Correlation of monoclonal and polyclonal somatostatin receptor 5 antibodies in pancreatic neuroendocrine tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Exp Pathol. 2013;6(1):49-54. Epub 2012 Nov 20.

AUTORES / AUTHORS:  - Kaemmerer D; Lupp A; Peter L; Fischer E; Schulz S; Kloppel G; Hommann M

INSTITUCIÓN / INSTITUTION:  - Department of General and Visceral Surgery, Zentralklinik Bad Berka Bad Berka, Germany. Daniel.Kaemmerer@zentralklinik.de

RESUMEN / SUMMARY:  - AIMS: To evaluate the frequency of somatostatin-receptor 5 (SSTR 5) in pancreatic neuroendocrine tumors by using monoclonal and polyclonal antibodies. MATERIAL AND METHOD: we analyzed 66 proven pancreatic neuroendocrine tumors immunohistochemically with monoclonal (clone UMB-4) and polyclonal SSTR 5-antibodies. Immunoreactive score (IRS) and DAKO-score Her2/neu were evaluated.  RESULTS: Immunohistochemistry analysis demonstrated for the IRS a significant higher staining of all specimen using the monoclonal antibodies ( IRS SSTR5 poly  vs IRS SSTR 5 mono; 20.0% vs 30.3% p < 0.001) by a correlation of 0.21; p = 0.04. For the HER2 score there was also a significant higher staining in the monoclonal group (Her2 SSTR 5 poly vs Her2 SSTR 5 mono; 21.5% vs 28.8% p < 0.001) by a correlation of 0.20; p = 0.08. CONCLUSION: Both antibodies are useful in staining of SSTR, although UMB-4 demonstrated a 10% higher SSTR 5 staining. Due to the previous underestimated expression rate of SSTR 5, current standards in diagnostics and therapy should be reconsidered. The increasing usage of long-acting pansomatostatin receptor analogues will rise the adverse effects connected to SSTR5 binding.

----------------------------------------------------

[354]

TÍTULO / TITLE:  - Pancreatic pseudocyst formation due to non-traumatic pancreatitis in a 3-year-old child.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2012 Nov 30;2012. pii: bcr2012006208. doi: 10.1136/bcr-2012-006208.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-006208

AUTORES / AUTHORS:  - Chaudhari HD; Bhatt CJ; Desai AB; Patel NK

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Smt. NHL Municipal Medical College, Ahmedabad, Gujarat,  India. drhdc1@yahoo.com

RESUMEN / SUMMARY:  - A pancreatic pseudocyst is a localised collection of pancreatic secretions that lacks a true epithelial lining and is walled off by granulation tissue. A rare case of pancreatic pseudocyst formation due to non-traumatic pancreatitis in a 3-year-old boy is described. The child was presented with fever, abdominal pain and vomiting for a period of 5 days. Ultrasonography and CT scan examinations were performed and biochemical and haematological investigations were undertaken. A pancreatic pseudocyst was identified and operatively managed by cystogastrostomy.

----------------------------------------------------

[355]

TÍTULO / TITLE:  - Solid pseudopapillary neoplasm of the pancreas in an old man: age does not matter.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pan Afr Med J. 2012;13:8. Epub 2012 Sep 11.

AUTORES / AUTHORS:  - Bouassida M; Mighri MM; Bacha D; Chtourou MF; Touinsi H; Azzouz MM; Sassi S

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Mohamed Tahar Maamouri Hospital, 8000 Mrazga, Nabeul, Tunisia.

RESUMEN / SUMMARY:  - Solid pseudopapillary tumor (SPN) of the pancreas is a rare tumor, but has favorable prognosis. It is typically observed in young women. Only few cases have been reported in young men. We report the observation of a 73-year-old man presented with a palpable mass in the left upper abdomen. CT scan showed 10 cm mass at the tail of the pancreas. This mass had mixed cystic and solid components. The patient underwent a distal pancreatectomy and splenectomy. SPN of the pancreas was diagnosed based on histopathological features. The patient recovered uneventfully and didn’t receive adjuvant therapy. A CT scan performed 16 months postoperatively showed no evidence of disease recurrence. Although SPN  of the pancreas is typically observed in young women, the diagnosis should not be discounted in old male patients. Male patients and those with old age, atypical histopathology and incomplete resection may have a higher risk of recurrence and  death, deserving particular attention.

----------------------------------------------------

[356]

TÍTULO / TITLE:  - Intraductal Delivery of Adenoviruses Targets Pancreatic Tumors in Transgenic Ela-myc Mice and Orthotopic Xenografts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncotarget. 2012 Jan 12.

AUTORES / AUTHORS:  - Jose A; Sobrevals L; Camacho-Sanchez JM; Huch M; Andreu N; Ayuso E; Navarro P; Alemany R; Fillat C

INSTITUCIÓN / INSTITUTION:  - Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona.

RESUMEN / SUMMARY:  - Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of  ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice  bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p<0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application  than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

----------------------------------------------------

[357]

TÍTULO / TITLE:  - Percutaneous fine needle biopsy in pancreatic tumors: a study of 42 cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastroenterol Res Pract. 2012;2012:908963. doi: 10.1155/2012/908963. Epub 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/908963

AUTORES / AUTHORS:  - Lewitowicz P; Matykiewicz J; Heciak J; Koziel D; Gluszek S

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Jan Kochanowski (UJK), Al. IX Wiekow Kielc 19, 25-317 Kielce, Poland.

RESUMEN / SUMMARY:  - The technological progress within the range of methods of pancreas imaging and their more common accessibility selects a group of patients requiring a microscopic diagnosis. Percutaneous fine needle aspiration biopsy under the control of ultrasonography (PCFNA/USG) is the method commonly used in determining the character of a focal pancreatic lesion. Aim of the Work. An assessment of the accessibility of PCFNA biopsy in the assessment of solid and cystic changes in a  pancreas and the correlation of the results of imaging examination, cytological smear and concentration of a serous marker CA19-9. Material and Methodology. In our material we analysed 43 cases of tumors of the pancreas among the patients who were at the average age of 59 +/- 10.4 (14 women, 28 men) diagnosed by PCFNA  biopsy. Results. In a group we are 23 cases of cancer, 12 cases of inflammation and 7 cases of cellular atypia for which 2 cases of IPMN were included. The sensitivity of the method was 92.5% but specificity was 68%. In our opinion PCFNA/USG is a method of the comparable sensitivity and specificity with fine needle aspiration biopsy with EUS control and its efficiency depends to a considerable degree on experience and interdisciplinary collaboration.

----------------------------------------------------

[358]

TÍTULO / TITLE:  - Complexity of molecular alterations impacts pancreatic cancer prognosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Gastrointest Oncol. 2013 Jan 15;5(1):1-3. doi: 10.4251/wjgo.v5.i1.1.

            ●● Enlace al texto completo (gratuito o de pago) 4251/wjgo.v5.i1.1

AUTORES / AUTHORS:  - Regel I; Kong B; Bruns P; Michalski CW; Kleeff J

INSTITUCIÓN / INSTITUTION:  - Ivonne Regel, Bo Kong, Philipp Bruns, Christoph W Michalski, Jorg Kleeff, Department of Surgery, Technische Universitat Munchen, 81675 Munchen, Germany.

RESUMEN / SUMMARY:  - Individualized cancer treatment (e.g. targeted therapy) based on molecular alterations has emerged as an important strategy to improve the current standard-of-care chemotherapy. A large number of studies have demonstrated the importance of biomarkers not only in predicting prognosis but more importantly in predicting the response towards therapies. For example, amplification or mutation status of the two biomarkers HER2 (human epidermal growth factor 2) and BRCA (breast cancer) can be used to decide on a specific targeted therapy in breast cancer. However, no biomarkers with a similar clinical impact have been identified in pancreatic ductal adenocarcinoma. Although many genome-wide and proteome-based high-throughput studies have identified candidate genes or proteins as promising biomarkers, none of them were eventually transferred into the clinical setting. Notably, the most reliable markers for predicting prognosis are still the tumor stage and grade and biomarkers for therapy response remain undefined. One reason lies in the lack of systemic approaches to analyze the complexity of dominating cancer pathways and the impact of such signal complexity on prognosis and therapy response.

----------------------------------------------------

[359]

TÍTULO / TITLE:  - Altered PTEN, ATRX, CHGA, CHGB, and TP53 Expression Are Associated with Aggressive VHL-Associated Pancreatic Neuroendocrine Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Horm Cancer. 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12672-013-0134-1

AUTORES / AUTHORS:  - Weisbrod AB; Zhang L; Jain M; Barak S; Quezado MM; Kebebew E

INSTITUCIÓN / INSTITUTION:  - Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.

RESUMEN / SUMMARY:  - Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome in which 8-17 %  of germline mutation carriers develop pancreatic neuroendocrine tumors (PNETs). There is limited data on prognostic markers for PNETs other than Ki-67, which is  included in the World Health Organization classification system. Recently, specific genes and pathways have been identified by whole exome sequencing which  may be involved in the tumorigenesis of PNETs and may be markers of disease aggressiveness. The objective of this study was to identify molecular markers of  aggressive disease in VHL-associated PNETs. The protein expression of eight genes (PTEN, CHGA, CHGB, ATRX, DAXX, CC-3, VEGF, and TP53) was analyzed in PNETs by immunohistochemistry and compared to clinical data, VHL genotype, functional imaging results, and pathologic findings. Subcellular distribution of phosphatase and tensin (PTEN), chromogranin A (CHGA), and alpha thalassemia/mental retardation syndrome X-linked (ATRX) were significantly different by WHO classifications (p </= 0.05). There was decreased PTEN nuclear to cytoplasmic ratio (p < 0.01) and decreased CHGA nuclear expression (p = 0.03) in malignant samples as compared to benign. Lower cytoplasmic chromogranin B (CHGB) expression (p = 0.03) was associated with malignant tumors and metastasis. Higher nuclear expression of PTEN was associated with VHL mutations in exon 3 (p = 0.04). Higher PTEN and CHGB expression was associated with higher FDG-PET avidity (p < 0.05). Cytoplasmic expression of CC-3 was associated with higher serum chromogranin A levels (rho = 0.72, p = 0.02). Lastly, greater cytoplasmic expression of p53 was  associated with metastasis. Our findings suggest that altered PTEN, ATRX, CHGA, and CHGB expression are associated with aggressive PNET phenotype in VHL and may  serve as useful adjunct prognostic markers to Ki-67 in PNETs.

----------------------------------------------------

[360]

TÍTULO / TITLE:  - Differential Processing of let-7a Precursors Influences RRM2 Expression and Chemosensitivity in Pancreatic Cancer: Role of LIN-28 and SET Oncoprotein.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e53436. doi: 10.1371/journal.pone.0053436. Epub 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053436

AUTORES / AUTHORS:  - Bhutia YD; Hung SW; Krentz M; Patel D; Lovin D; Manoharan R; Thomson JM; Govindarajan R

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutical and Biomedical Sciences, The University of Georgia,  Athens, Georgia, United States of America.

RESUMEN / SUMMARY:  - Overexpression of ribonucleotide reductase subunit M2 (RRM2), involved in deoxyribonucleotide synthesis, drives the chemoresistance of pancreatic cancer to nucleoside analogs (e.g., gemcitabine). While silencing RRM2 by synthetic means has shown promise in reducing chemoresistance, targeting endogenous molecules, especially microRNAs (miRNAs), to advance chemotherapeutic outcomes has been poorly explored. Based on computational predictions, we hypothesized that the let-7 tumor suppressor miRNAs will inhibit RRM2-mediated gemcitabine chemoresistance in pancreatic cancer. Reduced expression of the majority of let-7 miRNAs with an inverse relationship to RRM2 expression was identified in innately gemcitabine-resistant pancreatic cancer cell lines. Direct binding of let-7 miRNAs to the 3’ UTR of RRM2 transcripts identified post-transcriptional regulation of RRM2 influencing gemcitabine chemosensitivity. Intriguingly, overexpression of human precursor-let-7 miRNAs led to differential RRM2 expression and chemosensitivity responses in a poorly differentiated pancreatic cancer cell line, MIA PaCa-2. Defective processing of let-7a precursors to mature forms, in part, explained the discrepancies observed with let-7a expressional outcomes. Consistently, the ratios of mature to precursor let-7a were progressively reduced in gemcitabine-sensitive L3.6pl and Capan-1 cell lines induced to acquire gemcitabine resistance. Besides known regulators of let-7 biogenesis (e.g., LIN-28), short hairpin RNA library screening identified several novel RNA binding proteins, including the SET oncoprotein, to differentially impact let-7 biogenesis and chemosensitivity in gemcitabine-sensitive versus -resistant pancreatic cancer cells. Further, LIN-28 and SET knockdown in the cells led to profound reductions in cellular proliferation and colony-formation capacities. Finally, defective processing of let-7a precursors with a positive correlation to RRM2 overexpression was identified in patient-derived pancreatic ductal adenocarcinoma (PDAC) tissues. These data demonstrate an intricate post-transcriptional regulation of RRM2 and chemosensitivity by let-7a and that the manipulation of regulatory proteins involved in let-7a transcription/processing may provide a mechanism for improving chemotherapeutic and/or tumor growth control responses in pancreatic cancer.

----------------------------------------------------

[361]

TÍTULO / TITLE:  - Influence of diet and tobacco smoking on pancreatic cancer incidence in poland in 1960-2008.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastroenterol Res Pract. 2012;2012:682156. doi: 10.1155/2012/682156. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/682156

AUTORES / AUTHORS:  - Jarosz M; Sekula W; Rychlik E

INSTITUCIÓN / INSTITUTION:  - National Food and Nutrition Institute, Powsinska Street 61/63, 02-903 Warsaw, Poland.

RESUMEN / SUMMARY:  - The aim of the study was to investigate the relationship between pancreatic cancer incidence and selected dietary factors, alcohol consumption, and tobacco smoking in Poland in 1960-2008. Data on pancreatic cancer morbidity were derived  from the National Cancer Registry and on food consumption from the national food  balance sheets. In 1960-1989 correlations were found between pancreatic cancer incidence rates and energy (0.60 for males and 0.57 for females), cholesterol (0.87 and 0.80), fibre (-0.84 and -0.89) and folate (-0.45 and -0.49) intake, the consumption of total fats (0.94 and 0.91), animal fats (0,90 and 0,82), sugar (0.88 and 0.87), cereals (-0.93 and -0.91), and alcohol (0.86 and 0.82). In 1990-2008 morbidity correlated with the consumption of red meat (0.67 and 0.48),  poultry (-0.88 and -0.57), and fruit (-0.62 and -0.50). Correlation with tobacco  smoking was observed in the whole studied period (0.55 and 0.44). Increased incidence of pancreatic cancer in 1960-1995 was probably related to adverse dietary patterns up to 1989, especially high consumption of fats, sugar, and alcohol. Further positive changes in the diet such as lowering red meat consumption and increasing fruit consumption could influence incidence reduction  in recent years. Also changes in tobacco smoking could affect the morbidity.

----------------------------------------------------

[362]

TÍTULO / TITLE:  - Molecular Biologic Approach to the Diagnosis of Pancreatic Carcinoma Using Specimens Obtained by EUS-Guided Fine Needle Aspiration.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastroenterol Res Pract. 2012;2012:243524. doi: 10.1155/2012/243524. Epub 2012 Nov 8.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/243524

AUTORES / AUTHORS:  - Kato K; Kamada H; Fujimori T; Aritomo Y; Ono M; Masaki T

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa Prefecture, Takamatsu 761-0793, Japan.

RESUMEN / SUMMARY:  - We review the utility of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), a rapid, safe, cost-effective, and accurate diagnostic modality for evaluating pancreatic tumors. EUS-FNA is currently used for the diagnosis and staging of pancreatic tumors. The sensitivity of EUS-FNA for pancreatic malignancy ranges from 75% to 94%, and its specificity approaches 100% in most studies. However, EUS-FNA has some limitations in the diagnosis of well-differentiated or early-stage cancers. Recent evidence suggests that molecular biological analysis using specimens obtained by EUS-FNA improves diagnostic sensitivity and specificity, especially in borderline cytological cases. It was also reported that additional information regarding patient response to chemotherapy, surgical resectability, time to metastasis, and overall survival was acquired from the genetic analysis of specimens obtained by EUS-FNA. Other studies have revealed that the analysis of KRAS, MUC, p53, p16, S100P, SMAD4, and microRNAs is helpful in making the diagnosis of pancreatic carcinoma.  In this paper, we describe the present state of genetic diagnostic techniques for use with EUS-FNA samples in pancreatic diseases. We also discuss the role of molecular biological analyses for the diagnosis of pancreatic carcinoma.

----------------------------------------------------

[363]

TÍTULO / TITLE:  - One case of common bile duct cancer mimicking cystic neoplasm of the pancreas, arising 9 years after excision of a choledochal cyst.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Endosc. 2012 Nov;45(4):435-9. doi: 10.5946/ce.2012.45.4.435. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 5946/ce.2012.45.4.435

AUTORES / AUTHORS:  - Park SW; Lee SH; Eum YO; Oh HS; Lee D; Jin E; Chung K; Hwang JH

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

RESUMEN / SUMMARY:  - A 42-years-old woman had undergone operation for cholecochal cyst with gallbladder cancer 9 years ago. Pathology revealed a polypoid mass in the gallbladder with liver infiltration as poorly differentiated adenocarcinoma. Computed tomography, magnetic resonance cholangiopancreatography, and endoscopic  ultrasound showed a newly developed suspected solid nodule in the peripheral portion of cystic lesion in the pancreas head. She underwent a pylorus preserving pancreaticoduodenectomy for the suspected mucinous cystic neoplasm of the pancreas. Pathology revealed poorly differentiated adenocarcinoma. The remnant choledochal cyst had developed to cholangiocarcinoma, which mimicked cystic neoplasm of the pancreas.

----------------------------------------------------

[364]

TÍTULO / TITLE:  - Intraductal oncocytic papillary neoplasm of the pancreas: report of a case requiring completion pancreatectomy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JOP. 2013 Jan 10;14(1):77-80. doi: 10.6092/1590-8577/1259.

AUTORES / AUTHORS:  - Wohlauer MV; McManus M; Fukami N; Gajdos C

INSTITUCIÓN / INSTITUTION:  - Section of GI, Tumor and Endocrine Surgery, Department of Surgery, University of  Colorado at Denver. Aurora, CO, USA. csaba.gajdos@ucdenver.edu.

RESUMEN / SUMMARY:  - CONTEXT: Cystic tumors of the pancreas have been diagnosed with increasing frequency. Intraductal oncocytic papillary neoplasm is a rare type of cystic pancreatic tumor. Intraductal oncocytic papillary neoplasm is considered a distinct entity with the potential of developing into invasive carcinoma and it should be differentiated from other cystic tumors of the pancreas, including mucinous cystic neoplasm and other forms of intraductal papillary mucinous neoplasm (IPMN). Histologically, the formation of oncocytic cells and the complex morphology of the papillae distinguish intraductal oncocytic papillary neoplasm from IPMN. While the number of publications addressing the diagnosis, management  and follow-up of patients with IPMN has been increasing, the behavior differences between IPMN and intraductal oncocytic papillary neoplasm have not been elucidated, secondary to very limited clinical experience. CASE REPORT: Here, we  are presenting a case of a patient with the diagnosis of intraductal oncocytic papillary neoplasm of the pancreas developing into invasive cancer. CONCLUSION: This case stresses the necessity for lifelong surveillance of the remnant pancreas following partial pancreatectomy for intraductal oncocytic papillary neoplasm, due to the risk of developing multifocal disease.

----------------------------------------------------

[365]

TÍTULO / TITLE:  - Giant mucinous cystic neoplasms of pancreas and liver with unusual adipose tissue component: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Oncol. 2012 Dec;3(4):353-7. doi: 10.3978/j.issn.2078-6891.2012.010.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2078-6891.2012.010

AUTORES / AUTHORS:  - Ghatak S; Ray S; Sonar PK; Das S; Basu K; Mridha AR; Bhattacharyya A; Sarkar R

INSTITUCIÓN / INSTITUTION:  - School of digestive & liver diseases, Kolkata, West Bengal, India.

RESUMEN / SUMMARY:  - Simultaneous occurrence of pancreatic and hepatic mucinous cystic neoplasms is very rarely reported in the literature. We present a case with extensive fatty component of the pancreatic tumour arising from the head of the pancreas and attaining a huge size before being treated by Whipple’s pancreatoduodenectomy and subsequently by a right hepatectomy for the hepatic tumour.

----------------------------------------------------

[366]

TÍTULO / TITLE:  - Neoadjuvant chemotherapy with capecitabine and temozolomide for unresectable pancreatic neuroendocrine tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Oncol. 2012 Sep;5(3):622-6. doi: 10.1159/000345369. Epub 2012 Sep 20.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345369

AUTORES / AUTHORS:  - Devata S; Kim EJ

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Mich., USA.

RESUMEN / SUMMARY:  - Pancreatic neuroendocrine tumors (PNETs) are relatively rare tumors that arise in the endocrine cells of the pancreas. Historically, somatostatin analogues have been used in this disease primarily for symptom control and, to a limited extent, disease stability. More recently, sunitinib and everolimus have been approved for advanced stage PNETs based on a survival benefit. However, both agents have a <10% actual response rate and cause nontrivial side effect profiles that limit duration of therapy. In locally advanced disease, there is a paucity of data to support an optimal neoadjuvant approach with the expectation of down-staging to allow for curative resection. We describe in this case a young woman who was successfully down-staged using a chemotherapy regimen of capecitabine and temozolomide with minimal toxicity.

----------------------------------------------------

[367]

TÍTULO / TITLE:  - Salvage chemoradiotherapy after primary chemotherapy for locally advanced pancreatic cancer: a single-institution retrospective analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 20;12:609. doi: 10.1186/1471-2407-12-609.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-609

AUTORES / AUTHORS:  - Mayahara H; Ito Y; Morizane C; Ueno H; Okusaka T; Kondo S; Murakami N; Morota M; Sumi M; Itami J

INSTITUCIÓN / INSTITUTION:  - Division of Radiation Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. hmayahar@ncc.go.jp.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: There is no consensus on the indication for salvage chemoradiotherapy (CRT) after failure of primary chemotherapy for locally advanced pancreatic cancer (LAPC). Here we report on the retrospective analysis of patients who received salvage CRT after primary chemotherapy for LAPC. The primary objective of this study was to evaluate the efficacy and safety of salvage CRT after primary chemotherapy for LAPC. METHODS: Thirty patients who underwent salvage CRT, after the failure of primary chemotherapy for LAPC, were retrospectively enrolled from 2004 to 2011 at the authors’ institution. All the patients had histologically confirmed pancreatic adenocarcinoma. RESULTS: Primary chemotherapy was continued until progression or emergence of unacceptable toxicity. Eventually, 26 patients (87%) discontinued primary chemotherapy because of local tumor progression, whereas four patients (13%) discontinued chemotherapy because of interstitial pneumonitis caused by gemcitabine. After a median period  of 7.9 months from starting chemotherapy, 30 patients underwent salvage CRT combined with either S-1 or 5-FU. Toxicities were generally mild and self-limiting. Median survival time (MST) from the start of salvage CRT was 8.8 months. The 6 month, 1-year and 2-year survival rates from the start of CRT were  77%, 33% and 26%, respectively. Multivariate analysis revealed that a lower pre-CRT serum CA 19-9 level (</= 1000 U/ml; p = 0.009) and a single regimen of primary chemotherapy (p = 0.004) were independent prognostic factors for survival after salvage CRT. The MST for the entire patient population from the start of primary chemotherapy was 17.8 months, with 2- and 3-year overall survival rates of 39% and 22%, respectively. CONCLUSIONS: CRT had moderate anti-tumor activity and an acceptable toxicity profile in patients with LAPC, even after failure of gemcitabine-based primary chemotherapy. If there are any signs of failure of primary chemotherapy without distant metastasis, salvage CRT could be a treatment of choice as a second-line therapy. Patients with relatively low serum CA19-9 levels after primary chemotherapy may achieve higher survival rates after salvage CRT. The strategy of using chemotherapy alone as a primary treatment for LAPC, followed-by CRT with salvage intent should be further investigated in prospective clinical trials. TRIAL REGISTRATION: 2011-136.

----------------------------------------------------

[368]

TÍTULO / TITLE:  - Contrast-enhanced ultrasound for diagnosing, staging and assessment of operability of pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Dan Med J. 2012 Dec;59(12):B4536.

AUTORES / AUTHORS:  - Grossjohann HS

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Section of Ultrasound, Copenhagen University Hospital, Rigshospitalet, Denmark. hannesonder@dadlnet.dk.

RESUMEN / SUMMARY:  - We have evaluated the usefulness of contrast-enhanced ultrasound (CEUS) for diagnosing, staging and assessment of operability of pancreatic head tumors. For  some years CEUS has been used with great success for diagnosis of focal liver lesions but when we started our trial, it was still relatively untested in the pancreas. This PhD thesis is based on a methodological study, two clinical studies and an intra-/interobserver study. The methodological study consists of material collected from investigations made on 14 experimental pigs. First, we examined the pig pancreas with CEUS. Hereafter we repeated the CEUS examination after venous injection of the gastrointestinal hormones secretin and cholecystokinin. We investigated if the contrast-enhancement would intensify after hormone stimulation. The clinical studies consist of material collected from examinations of 49 patients referred to our hospital with the diagnosis, suspicion of pancreatic cancer. All patients had a conventional ultrasound examination and a CEUS examination. In addition, some of the patients also had a  CEUS examination after stimulation with secretin and cholecystokinin. All patients had a 64-slice-CT examination and a biopsy was taken for histopathological verification. We studied whether CEUS was useful for assessment of tumor classification, tumor staging and tumor resectability. We also tested if hormone stimulation of the pancreas during CEUS could intensify contrast-enhancement of healthy pancreatic tissue and thus contribute to a better demarcation of a tumor. Finally, we tested the intra-/interobserver agreement of  our visual interpretation of the contrast-enhanced ultrasound images and the concordance between the visual interpretation and histopathological test results. From the results of the methodological study it seemed possible to intensify contrast-enhancement using the gastrointestinal hormones by 3%. During the clinical studies it emerged that hormone stimulation did not improve the visual impression of the CEUS examinations in any cases. We found that CEUS may be a useful diagnostic tool in the diagnosis of pancreatic head tumors, with a sensitivity of 86% (CI: 79-96) in the diagnosis of pancreatic adenocarcinomas with histopathology as gold standard. Our intra-/interobserver agreements of the  visual interpretation of tumor enhancement using CEUS showed substantial or almost perfect agreement with kappa values between 0.75 and 0.89. CEUS was useful for assessment of liver metastases but not as useful for assessment of the local  tumor area and thereby not very useful for assessment of tumor resectability. By  performing the US+CEUS and 64-CT we additionally found 35% and 45% respectively nonresectable patients of a group of patients, who were considered resectable on  the primary radiological image material. In conclusion this thesis points to CEUS as a useful but not sufficient tool in the diagnosis, staging and assessment of operability of patients with pancreatic cancer.

----------------------------------------------------

[369]

TÍTULO / TITLE:  - Notch3 and HEY-1 as prognostic biomarkers in pancreatic adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e51119. doi: 10.1371/journal.pone.0051119. Epub 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051119

AUTORES / AUTHORS:  - Mann CD; Bastianpillai C; Neal CP; Masood MM; Jones DJ; Teichert F; Singh R; Karpova E; Berry DP; Manson MM

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, Leicestershire, United Kingdom.

RESUMEN / SUMMARY:  - In order to achieve a better outcome for pancreatic cancer patients, reliable biomarkers are required which allow for improved diagnosis. These may emanate from a more detailed molecular understanding of the aggressive nature of this disease. Having previously reported that Notch3 activation appeared to be associated with more aggressive disease, we have now examined components of this  pathway (Notch1, Notch3, Notch4, HES-1, HEY-1) in more detail in resectable (n =  42) and non-resectable (n = 50) tumours compared to uninvolved pancreas. All three Notch family members were significantly elevated in tumour tissue, compared to uninvolved pancreas, with expression maintained within matched lymph node metastases. Furthermore, significantly higher nuclear expression of Notch1, -3 and -4, HES-1, and HEY-1 (all p </= 0.001) was noted in locally advanced and metastatic tumours compared to resectable cancers. In survival analyses, nuclear  Notch3 and HEY-1 expression were significantly associated with reduced overall and disease-free survival following tumour resection with curative intent, with nuclear HEY-1 maintaining independent prognostic significance for both outcomes on multivariate analysis. These data further support a central role for Notch signalling in pancreatic cancer and suggest that nuclear expression of Notch3 and its target gene, HEY-1, merit validation in biomarker panels for diagnosis, prognosis and treatment efficacy. A peptide fragment of Notch3 was detected in plasma from patients with inoperable pancreatic cancer, but due to wide inter-individual variation, mean levels were not significantly different compared to age-matched controls.

----------------------------------------------------

[370]

TÍTULO / TITLE:  - Aberrant glycogen synthase kinase 3beta in the development of pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Carcinog. 2012;11:15. doi: 10.4103/1477-3163.100866. Epub 2012 Sep 13.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1477-3163.100866

AUTORES / AUTHORS:  - Shimasaki T; Kitano A; Motoo Y; Minamoto T

INSTITUCIÓN / INSTITUTION:  - Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University and Hospital, 13-1 Takara-machi, Kanazawa 920-0934, Japan ; Division of Translational and Clinical Oncology, Cancer Research Institute and Cancer Center, Kanazawa University and Hospital, 13-1 Takara-machi, Kanazawa 920-0934, Japan.

RESUMEN / SUMMARY:  - Development and progression of pancreatic cancer involves general metabolic disorder, local chronic inflammation, and multistep activation of distinct oncogenic molecular pathways. These pathologic processes result in a highly invasive and metastatic tumor phenotype that is a major obstacle to curative surgical intervention, infusional gemcitabine-based chemotherapy, and radiation therapy. Many clinical trials with chemical compounds and therapeutic antibodies  targeting growth factors, angiogenic factors, and matrix metalloproteinases have  failed to demonstrate definitive therapeutic benefits to refractory pancreatic cancer patients. Glycogen synthase kinase 3beta (GSK3beta), a serine/threonine protein kinase, has emerged as a therapeutic target in common chronic and progressive diseases, including cancer. Here we review accumulating evidence for  a pathologic role of GSK3beta in promoting tumor cell survival, proliferation, invasion, and resistance to chemotherapy and radiation in pancreatic cancer. We also discuss the putative involvement of GSK3beta in mediating metabolic disorder, local inflammation, and molecular alteration leading to pancreatic cancer development. Taken together, we highlight potential therapeutic as well as preventive effects of GSK3beta inhibition in pancreatic cancer.

----------------------------------------------------

[371]

TÍTULO / TITLE:  - Silk fibroin hydrolysate exerts an anti-diabetic effect by increasing pancreatic  beta cell mass in C57BL/KsJ-db/db mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Vet Sci. 2012 Dec;13(4):339-44.

AUTORES / AUTHORS:  - Do SG; Park JH; Nam H; Kim JB; Lee JY; Oh YS; Suh JG

INSTITUCIÓN / INSTITUTION:  - Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon 200-702, Korea.

RESUMEN / SUMMARY:  - Components of silk including silk fibroin have long been used as anti-diabetic remedies in oriental medicine. However, detailed mechanisms underlying these antidiabetic effects remain unclear. In this study, we examined the anti-diabetic activity of silk fibroin hydrolysate (SFH) in C57BL/KsJ db/db (db/db) mice, a well-known animal model of non-insulin dependent diabetes mellitus. When the db/db mice were administered SFH in drinking water for 6 weeks, hyperglycemia in  the animals gradually disappeared and the level of glycosylated hemoglobin decreased, indicating that SFH plays important role in reducing the symptoms of diabetes. In addition, SFH-treated db/db mice exhibited improved glucose tolerance with increased plasma insulin levels. Immunohistochemical and morphological analyses showed that SFH up-regulated insulin production by increasing pancreatic beta cell mass in the mice. In summary, our results suggest that SFH exerts anti-diabetic effects by increasing pancreatic beta cell mass in  a non-insulin dependent diabetes mellitus mouse model.

 

----------------------------------------------------

[372]

TÍTULO / TITLE:  - Metastatic pancreatic cancer is dependent on oncogenic Kras in mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e49707. doi: 10.1371/journal.pone.0049707. Epub 2012 Dec 3.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0049707

AUTORES / AUTHORS:  - Collins MA; Brisset JC; Zhang Y; Bednar F; Pierre J; Heist KA; Galban CJ; Galban S; di Magliano MP

INSTITUCIÓN / INSTITUTION:  - Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan, United States of America.

RESUMEN / SUMMARY:  - Pancreatic cancer is one of the deadliest human malignancies, and its prognosis has not improved over the past 40 years. Mouse models that spontaneously develop  pancreatic adenocarcinoma and mimic the progression of the human disease are emerging as a new tool to investigate the basic biology of this disease and identify potential therapeutic targets. Here, we describe a new model of metastatic pancreatic adenocarcinoma based on pancreas-specific, inducible and reversible expression of an oncogenic form of Kras, together with pancreas-specific expression of a mutant form of the tumor suppressor p53. Using  high-resolution magnetic resonance imaging to follow individual animals in longitudinal studies, we show that both primary and metastatic lesions depend on  continuous Kras activity for their maintenance. However, re-activation of Kras* following prolonged inactivation leads to rapid tumor relapse, raising the concern that Kras*-resistance might eventually be acquired. Thus, our data identifies Kras* as a key oncogene in pancreatic cancer maintenance, but raises the possibility of acquired resistance should Kras inhibitors become available for use in pancreatic cancer.

----------------------------------------------------

[373]

TÍTULO / TITLE:  - Pancreatic tumor preparation in mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cold Spring Harb Protoc. 2012 Dec 1;2012(12). pii: pdb.prot072363. doi: 10.1101/pdb.prot072363.

            ●● Enlace al texto completo (gratuito o de pago) 1101/pdb.prot072363

AUTORES / AUTHORS:  - Jain RK; Munn LL; Fukumura D

RESUMEN / SUMMARY:  - Pancreatic cancer has a poor prognosis, and treatment strategies conducted from preclinical research have not succeeded in extending a patient’s survival appreciably. This protocol describes how to prepare an abdominal window in mice.  This allows both direct intravital microscopy and chronic observation during pancreas tumor growth and the response to treatment.

----------------------------------------------------

[374]

TÍTULO / TITLE:  - Pancreatic cancer: Endoscopic-ultrasonography-guided fine-needle aspiration is effective for diagnosing pancreatic cystic neoplasms.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Gastroenterol Hepatol. 2013 Jan 15. doi: 10.1038/nrgastro.2013.4.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrgastro.2013.4

----------------------------------------------------

[375]

TÍTULO / TITLE:  - Towards pancreatic cancer diagnosis using EIS biochips.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lab Chip. 2013 Jan 22;13(4):730-4. doi: 10.1039/c2lc41127j.

            ●● Enlace al texto completo (gratuito o de pago) 1039/c2lc41127j

AUTORES / AUTHORS:  - Chiriaco MS; Primiceri E; Monteduro AG; Bove A; Leporatti S; Capello M; Ferri-Borgogno S; Rinaldi R; Novelli F; Maruccio G

INSTITUCIÓN / INSTITUTION:  - NNL Istituto Nanoscienze - CNR and Dipartimento di Matematica e Fisica “Ennio De  Giorgi”, Scuola Superiore ISUFI, Universita del Salento, Via per Arnesano, I-73100 Lecce, Italy. serena.chiriaco@unisalento.it giuseppe.maruccio@unisalento.it.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal  cancers in Europe and the United States. It has a very low 5 years-survival rate  and its diagnosis is often late and imprecise due to the lack of specificity of currently used markers for PDAC. As previously demonstrated PDAC patients’ sera may contain autoantibodies towards phosphorylated alpha-enolase (ENOA), which in  combination with other standard markers can increase specificity in diagnosis of  PDAC. In this context we realized a microfluidic platform with integrated EIS biosensors. We achieved a specific antibodies detection by immobilizing onto electrodes peptides corresponding to a portion of ENOA. Phosphorylation of peptides was found to influence the recognition of antibodies in PDAC patients’ sera detected by the developed biochip thus validating the EIS technique as a strong tool for quick, cost-saving and label-free analysis of serum samples. Biochip results are in agreement with those from traditional techniques, such as  ELISA and western blot, but measurements are much more sensitive and specific, increasing the possibility of PDAC diagnosis. In addition this approach is faster and more reproducible compared to traditional techniques making the developed biochips ideal for a quick, cost-saving and label-free analysis of serum samples.

----------------------------------------------------

[376]

TÍTULO / TITLE:  - Quantitative Targeted Absolute Proteomics-Based Large-Scale Quantification of Proline-Hydroxylated alpha-Fibrinogen in Plasma for Pancreatic Cancer Diagnosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Proteome Res. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1021/pr3008144

AUTORES / AUTHORS:  - Yoneyama T; Ohtsuki S; Ono M; Ohmine K; Uchida Y; Yamada T; Tachikawa M; Terasaki T

INSTITUCIÓN / INSTITUTION:  - Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University , Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.

RESUMEN / SUMMARY:  - Pancreatic cancer is a devastating disease and early diagnosis and treatment are  essential to improve the prognosis. We previously showed that alpha-fibrinogen containing hydroxylated proline residues at positions 530 and 565 is increased in plasma of pancreatic cancer patients. However, no antibody specific for hydroxylated proline-530 is available. Therefore, the purposes of this study were to develop a quantification method specific for both proline-hydroxylated alpha-fibrinogens by selected/multiple reaction monitoring (SRM/MRM), and to validate these modifications as pancreatic cancer markers. The target peptide for hydroxylated proline-530 contained methionine, and since variable partial oxidation of this residue would affect the quantification, hydrogen peroxide treatment was carried out to ensure complete oxidation. Quantification values of  modified and unmodified alpha-fibrinogen were well correlated with those obtained by immunoblotting. Concentrations of modified and unmodified alpha-fibrinogen were quantified in 70 pancreatic cancer patients and 27 healthy controls. Percent hydroxylation of alpha-fibrinogen and concentration of hydroxylated alpha-fibrinogen were significantly greater in the plasma of patients. Furthermore, among 8 carbohydrate antigen 19-9 (CA19-9)-negative patients in stages I/II, 6 were positive for proline-hydroxylated alpha-fibrinogen. These results indicate that plasma concentration of proline-hydroxylated alpha-fibrinogen measured by SRM/MRM analysis may be a good pancreatic cancer marker, especially in CA19-9-negative patients.

----------------------------------------------------

[377]

TÍTULO / TITLE:  - FNA diagnosis of osteoclast-like giant cell tumor of the pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cytol. 2012 Oct;29(4):270-2. doi: 10.4103/0970-9371.103951.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0970-9371.103951

AUTORES / AUTHORS:  - Sivanandham S; Subashchandrabose P; Muthusamy KR

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India.

RESUMEN / SUMMARY:  - Osteoclast-like giant cell tumor of the pancreas is a rare non-endocrine neoplasm composed of reactive multinucleated giant cells admixed with mononuclear stromal  cells. We report a case of osteoclast-like giant cell tumor of the pancreas in a  58-year-old female with vague clinical symptoms. Endoscopic ultrasound-guided aspirate from the mass revealed numerous characteristic osteoclast-like giant cells.

----------------------------------------------------

[378]

TÍTULO / TITLE:  - Necrolytic migratory erythema associated with glucagonoma syndrome diagnosed by (68) Ga-DOTANOC PET-CT.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asia Pac J Clin Oncol. 2012 Dec 26. doi: 10.1111/ajco.12048.

            ●● Enlace al texto completo (gratuito o de pago) 1111/ajco.12048

AUTORES / AUTHORS:  - Sahoo MK; Gupta S; Singh I; Pahwa S; Durgapal P; Bal CS

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

RESUMEN / SUMMARY:  - Necrolytic migratory erythema (NME) is a rare dermatological condition which presents a diagnostic challenge. Repeated negative skin biopsies and non-detection of any pancreatic tumor in conventional imaging modalities like a computed tomography (CT) scan and ultrasonogram (USG) make the diagnosis more difficult. By the time the diagnosis is made, the patient usually presents with metastasis. We present a rare case of difficult to diagnose NME, as repeated skin biopsies and conventional imaging modalities like CT and USG could not detect the underlying glucagonoma. A (68) Ga-DOTANOC positron emission tomography PET-CT was able to detect the underlying cause of NME as glucagonoma of the pancreas and the same investigation confirmed the absence of any metastasis elsewhere in the body. The tumor was excised and patient dramatically improved, and all skin lesions disappeared.

----------------------------------------------------

[379]

TÍTULO / TITLE:  - SOX4 Transcriptionally Regulates Multiple SEMA3/Plexin Family Members and Promotes Tumor Growth in Pancreatic Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e48637. doi: 10.1371/journal.pone.0048637. Epub 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0048637

AUTORES / AUTHORS:  - Huang HY; Cheng YY; Liao WC; Tien YW; Yang CH; Hsu SM; Huang PH

INSTITUCIÓN / INSTITUTION:  - Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China ; Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.

RESUMEN / SUMMARY:  - Semaphorin signaling through Plexin frequently participates in tumorigenesis and  malignant progression in various types of cancer. In particular, the role of semaphorin signaling in pancreatic ductal adenocarcinoma (PDAC) remains unexplored, despite a high likelihood of metastasis and mortality. Unlike other epithelial malignancies that often express a small number of specific genes in the Semaphorin/Plexin family, five or more are often expressed in human PDAC. Such concomitant expression of these SEMA3/Plexin family members is not a result  of gene amplification, but (at least partially) from increased gene transcription activated by SOX4 de novo expressed in PDAC. Via chromatin-immunoprecipitation, luciferase promoter activity assay and electrophoresis mobility shift assay, SOX4 is demonstrated to bind to the consensus site at the promoter of each SEMA3 and Plexin gene to enhance transcription activity. Conversely, RNAi-knockdown of SOX4 in PDAC cell lines results in decreased expression of SEMA3/Plexin family members and is associated with restricted tumor growth both in vitro and in SCID mice. We further demonstrate that SOX4 levels parallel with the summed expression of SEMA3/Plexin family members (P = 0.033, NPar Kruskal-Wallis one-way analysis), which also correlates with poor survival in human PDAC (P = 0.0409, Kaplan-Meier  analysis). Intriguingly, miR-129-2 and miR-335, both of which target SOX4 for degradation, are co-repressed in human PDAC cases associated with up-regulated SOX4 in a statistically significant way. In conclusion, we disclose a miR-129-2(miR-335)/SOX4/Semaphorin-Plexin regulatory axis in the tumorigenesis of pancreatic cancer.

----------------------------------------------------

[380]

TÍTULO / TITLE:  - Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by  capsaicin in the human pancreatic cancer cell line PANC-1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):43-48. Epub 2012 Oct 24.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.991

AUTORES / AUTHORS:  - Zhang JH; Lai FJ; Chen H; Luo J; Zhang RY; Bu HQ; Wang ZH; Lin HH; Lin SZ

INSTITUCIÓN / INSTITUTION:  - Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325027;

RESUMEN / SUMMARY:  - Capsaicin, one of the major pungent ingredients found in red peppers, has been recently demonstrated to induce apoptosis in various malignant cell lines through an unclear mechanism. In this study, the effect of capsaicin on proliferation and apoptosis in the human pancreatic cancer cell line PANC-1 and its possible mechanism(s) of action were investigated. The results of a Cell Counting Kit-8 (CCK-8) assay revealed that capsaicin significantly decreased the viability of PANC-1 cells in a dose-dependent manner. Capsaicin induced G0/G1 phase cell cycle arrest and apoptosis in PANC-1 cells as demonstrated by a flow cytometric assessment. Caspase-3 expression at both the protein and mRNA level was promoted  following capsaicin treatment. Furthermore, we revealed that phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473) in PANC-1 cells were downregulated in response to capsaicin. Moreover, capsaicin gavage significantly inhibited the growth of pancreatic cancer PANC-1 cell xenografts in athymic nude mice. An increased number of TUNEL-positive cells and cleaved caspase-3 were observed in capsaicin-treated mice. In vivo, capsaicin downregulated the expression of phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473). In conclusion, we have  demonstrated that capsaicin is an inhibitor of growth of PANC-1 cells, and downregulation of the phosphoinositide 3-kinase/Akt pathway may be involved in capsaicin-induced apoptosis in vitro and in vivo.

----------------------------------------------------

[381]

TÍTULO / TITLE:  - Insulinoma causing liver metastases 15 years after initial surgery, accompanied by glomerulonephritis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Report Endocrinol. 2012;2012:168671. doi: 10.1155/2012/168671. Epub 2012 Dec 3.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/168671

AUTORES / AUTHORS:  - Janez A

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical  Center Ljubljana, Zaloska 7, 1000 Ljubljana, Slovenia.

RESUMEN / SUMMARY:  - Insulinoma is a rare pancreatic endocrine tumor that is typically sporadic, solitary, and less than 2 cm in diameter. Ninety percent of all insulinomas are benign. Up to 10 percent are malignant and are usually larger in size. We report  a case of an unusual, not yet described association of two diseases: a malignant  pancreatic insulinoma recurred as a multiple liver metastasis 15 years after the  initial complete enucleation of a primary tumor with a histomorphological fairly  benign outlook, accompanied by ANCA positive crescentic glomerulonephritis.

----------------------------------------------------

[382]

TÍTULO / TITLE:  - Is there a ‘margin’ for error in pancreatic cancer surgery?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Future Oncol. 2013 Jan;9(1):31-4. doi: 10.2217/fon.12.175.

            ●● Enlace al texto completo (gratuito o de pago) 2217/fon.12.175

AUTORES / AUTHORS:  - Frampton AE; Gall TM; Krell J; Ahmad R; Jiao LR

INSTITUCIÓN / INSTITUTION:  - HPB Surgical Unit, Department of Surgery & Cancer, Imperial College, Hammersmith  Hospital campus, Du Cane Road, London, W12 0HS, UK.

RESUMEN / SUMMARY:  - Evaluation of: Gnerlich JL, Luka SR, Deshpande AD et al. Microscopic margins and  patterns of treatment failure in resected pancreatic adenocarcinoma. Arch. Surg.  147(8), 753-760 (2012). Pancreatic ductal adenocarcinoma (PDAC) is a devastating  disease with one of the worst 5-year survival rates of any malignancy. Even after potentially curative surgical resection, disease may progress rapidly. It is therefore important to identify clinicopathologic factors that influence survival and may be modified to improve outcomes. The evaluated article presents data from a retrospective review of patients who underwent surgical resection for PDAC. Local recurrence (LR), distant recurrence and survival were compared between patients with a negative resection margin (R0) and those with a positive resection margin (R1). Patients with R1 posterior margins, in particular, were more likely to have LR and worse LR-free survival. In addition, this was more pronounced if patients had lymph-node involvement. Similar results have been reported in other studies and this study illustrates that standardized pathological reporting of PDAC specimens may allow further investigation of factors affecting R1 patients.

----------------------------------------------------

[383]

TÍTULO / TITLE:  - MACC1: A potential molecule associated with pancreatic cancer metastasis and chemoresistance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Oct;4(4):783-791. Epub 2012 Jul 2.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.784

AUTORES / AUTHORS:  - Wang G; Kang MX; Lu WJ; Chen Y; Zhang B; Wu YL

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Cancer Institute of Zhejiang University, Hangzhou, Zhejiang  310009, P.R. China.

RESUMEN / SUMMARY:  - It has been suggested that the newly identified metastasis-associated in colon cancer-1 (MACC1) oncogene is involved in the progression and metastasis of cancer. Several studies have indicated that MACC1 has potential as a novel biomarker. In this study, we aimed to investigate the functions and serum expression levels of MACC1 in pancreatic cancer patients. Blood serum samples from 60 cancer patients and 49 controls were analyzed for serum MACC1 by ELISA. The results revealed that high expression levels of MACC1 were correlated with lymph node metastasis, distant metastasis and a later TNM stage. Inhibition of MACC1 by siRNAs significantly suppressed pancreatic cancer cell proliferation and migration. Furthermore, it was found that the downregulation of MACC1 sensitized  pancreatic cancer cells to gemcitabine treatment through the inhibition of the Ras/ERK signaling pathway. Our findings suggest that MACC1 may aid in the diagnosis of pancreatic cancer and serve as a potential therapeutic target.

----------------------------------------------------

[384]

TÍTULO / TITLE:  - Differentiating Branch Duct and Mixed IPMN in Endoscopically Collected Pancreatic Cyst Fluid via Cytokine Analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastroenterol Res Pract. 2012;2012:247309. doi: 10.1155/2012/247309. Epub 2012 Dec 25.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/247309

AUTORES / AUTHORS:  - Lee LS; Bellizzi AM; Banks PA; Sainani NI; Kadiyala V; Suleiman S; Conwell DL; Paulo JA

INSTITUCIÓN / INSTITUTION:  - Center for Pancreatic Disease and Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.

RESUMEN / SUMMARY:  - Background. Differentiating branch duct from mixed intraductal papillary mucinous neoplasm (BD-IPMN) is problematic, but clinically important as mixed IPMNs are managed surgically, while some BD-IPMN may be followed. Inflammatory mediator proteins (IMPs) have been implicated in acute and chronic inflammatory and malignant pancreatic diseases. Aim. To compare IMP profile of pancreatic cyst fluid collected endoscopically from BD-IPMN and mixed IPMN. Methods. Pancreatic cyst fluid from ten patients (5 BD-IPMN and 5 mixed IPMN) was collected by endoscopic ultrasound-guided fine needle aspiration or endoscopic retrograde cholangiopancreatography. Concentrations of 89 IMPs in these samples were determined using a multiplexed bead-based microarray protein assay and compared between BD-IPMN and mixed IPMN. Results. Eighty-six of 89 IMPs were detected in at least one of the 10 samples. Fourteen IMPs were detected only in mixed IPMN, while none were only in BD-IPMN. Of these, TGF-beta1 was most prevalent, present  in 3 of 5 mixed IPMNs. Seventy-two IMPs were detected in both BD-IPMN and mixed IPMNs. Of these, only G-CSF (P < 0.05) was present in higher concentrations in mixed IPMNs. Conclusion. TGF-beta1 and G-CSF detected in endoscopically collected pancreatic cyst fluid are potential diagnostic biomarkers capable of distinguishing mixed IPMN from BD-IPMN.

----------------------------------------------------

[385]

TÍTULO / TITLE:  - Biliary stents for pancreas cancer with obstruction: the problem with plastic.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Oncol. 2012 Dec;3(4):306-8. doi: 10.3978/j.issn.2078-6891.2012.047.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2078-6891.2012.047

AUTORES / AUTHORS:  - Boulay BR

INSTITUCIÓN / INSTITUTION:  - Section of Digestive Diseases & Nutrition, University of Illinois Hospital & Health Sciences System, Chicago, Illinois USA.

----------------------------------------------------

[386]

TÍTULO / TITLE:  - Cadmium exposure and pancreatic cancer in South louisiana.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Environ Public Health. 2012;2012:180186. doi: 10.1155/2012/180186. Epub 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/180186

AUTORES / AUTHORS:  - Luckett BG; Su LJ; Rood JC; Fontham ET

INSTITUCIÓN / INSTITUTION:  - Epidemiology Program, School of Public Health, Louisiana State University Health  Sciences Center, 2020 Gravier Street, 3rd Floor, New Orleans, LA 70112, USA ; Department of Global Community Health and Behavioral Sciences, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, Suite 2300, New Orleans, LA 70112, USA.

RESUMEN / SUMMARY:  - Cadmium has been hypothesized to be a pancreatic carcinogen. We test the hypothesis that cadmium exposure is a risk factor for pancreatic cancer with a population-based case-control study sampled from a population with persistently high rates of pancreatic cancer (south Louisiana). We tested potential dietary and nondietary sources of cadmium for their association with urinary cadmium concentrations which reflect long-term exposure to cadmium due to the accumulation of cadmium in the kidney cortex. Increasing urinary cadmium concentrations were significantly associated with an increasing risk of pancreatic cancer (2nd quartile OR = 3.34, 3rd = 5.58, 4th = 7.70; test for trend P </= 0.0001). Potential sources of cadmium exposure, as documented in the scientific literature, found to be statistically significantly associated with increased risk of pancreatic cancer included working as a plumber, pipefitter or  welder (OR = 5.88) and high consumption levels of red meat (4th quartile OR = 6.18) and grains (4th quartile OR = 3.38). Current cigarette smoking, at least 80 pack years of smoking, occupational exposure to cadmium and paints, working in a  shipyard, and high consumption of grains were found to be statistically significantly associated with increased concentrations of urinary cadmium. This study provides epidemiologic evidence that cadmium is a potential human pancreatic carcinogen.

----------------------------------------------------

[387]

TÍTULO / TITLE:  - Cyst fluid carcinoembryonic antigen concentration and cytology by endosonography-guided fine needle aspiration in predicting maglinant pancreatic mucinous cystic neoplasms.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Dig Dis. 2012 Dec 25. doi: 10.1111/1751-2980.12027.

            ●● Enlace al texto completo (gratuito o de pago) 1111/1751-2980.12027

AUTORES / AUTHORS:  - Zhan XB; Wang B; Liu F; Ye XF; Jin ZD; Li ZS

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Changhai Hospital.

RESUMEN / SUMMARY:  - OBJECTIVE: To assess the value of CEA level and cytology examination obtained by  endosonography-guided fine needle aspiration (EUS-FNA) in predicting the malignancy of pancreatic mucinous cystic neoplasms (MCNs). METHODS: The data of patients with pancreatic MCNs who underwent EUS-FNA in Changhai Hospital, Second  Military Medical Univesrity (Shanghai, China) from November 2005 to April 2010 were collected and analyzed. The area under the receiver operating characteristics curve, sensitivity, specificity, positive predictive value (PPV)  and negative predictive value (NPV) of the cytology as well as cyst fluid CEA were determined. RESULTS: Of the total 20 MCNs confirmed by surgical pathology, 10 were malignant and the other 10 were premalignant. Cytology had some value in  differentiating malignant from premalignant MCNs with a sensitivity of 60%, specificity of 100%, PPV of 100%, and NPV of 71.4%. CEA with a cut-off value of 692.8 ng/mL was able to predict malignancy (P = 0.007) with sensitivity of 80.0%, specificity of 90.0%, PPV of 88.9% and NPV of 81.8%. CONCLUSION: Cyst fluid CEA levels and cytology obtained by EUS-FNA are useful to predict the malignancy of pancreatic MCNs.

----------------------------------------------------

[388]

TÍTULO / TITLE:  - Anterior mediastinal gastroenteric cyst containing pancreatic tissue influenced the diabetes mellitus status.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Interact Cardiovasc Thorac Surg. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1093/icvts/ivs496

AUTORES / AUTHORS:  - Shoji F; Takeo S; Shikada Y; Katsura M

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.

RESUMEN / SUMMARY:  - The mediastinal gastroenteric cyst is a rare developmental cyst. In general, the  majority of mediastinal gastroenteric cysts are recognized in infancy and are commonly located in the posterior mediastinum. In addition, gastroenteric cysts occasionally contain pancreatic tissue; however, no studies have reported that these cysts influenced the diabetes mellitus status of the patient. We report here an extremely rare case of an adult gastroenteric cyst with pancreatic tissue originating from the anterior mediastinum, influencing the severity of diabetes mellitus in a patient. This case report presents two remarkable findings. First,  the location of the gastroenteric cyst (anterior mediastinum) and the patient’s age at the time of detection (adulthood) were extremely rare. Secondly, the present case is also unusual in terms of glycometabolism. As this tumour decreased in size, the glycosylated haemoglobin value increased, which suggested  a worsening of the patient’s diabetes mellitus. The diabetes mellitus further worsened after removal of the tumour.

----------------------------------------------------

[389]

TÍTULO / TITLE:  - Pancreatic pseudocyst after endoscopic ultrasound-guided fine needle aspiration of pancreatic mass.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Endosc. 2012 Nov;45(4):431-4. doi: 10.5946/ce.2012.45.4.431. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 5946/ce.2012.45.4.431

AUTORES / AUTHORS:  - Chung KH; Ryu JK; Oh HS; Seo JY; Jin E; Lee DH; Kim YT; Yoon YB

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is well known as a  safe diagnostic procedure. We report the first case of pancreatic pseudocyst after EUS-FNA of the pancreatic body mass. A 60-year-old male underwent EUS-FNA for incidentally detected pancreatic solid mass which was suspected as neuroendocrine tumor. Two weeks later, the patient visited emergency room with acute abdominal pain and right upper quadrant tenderness; leukocytosis and elevated C-reactive protein, amylase, and lipase levels were noted. Computed tomography discovered newly developed 11.5x9.5 cm sized cystic mass communicating with the main pancreatic duct. Cyst fluid analysis revealed amylase level of 3,423 U/L and fluid culture isolated Streptococcus parasanguinis. The cystic mass corresponds with pancreatic pseudocyst. FNA induced main pancreatic duct injury and fluid leakage may cause it. Endoscopists who perform EUS-FNA must remember that pancreatic main duct injury can occur as one of severe complications and that it could be treated successfully with endoscopic internal drainage.

----------------------------------------------------

[390]

TÍTULO / TITLE:  - In vitro study of SPIO-labeled human pancreatic cancer cell line BxPC-3.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Contrast Media Mol Imaging. 2013 Mar;8(2):101-7. doi: 10.1002/cmmi.1499.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cmmi.1499

AUTORES / AUTHORS:  - Tong M; Xiong F; Shi Y; Luo S; Liu Z; Wu Z; Wang Z

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, People’s Republic of China; Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, People’s Republic of China.

RESUMEN / SUMMARY:  - The survivin gene is highly expressed in pancreatic cancer. The purpose of this study was to design and synthesize functionalized magnetic iron oxide nanoparticles (MNPs) targeting survivin gene for the detection of pancreatic cancer. The pancreatic cancer cell line BxPC-3 with survivin gene expression was  selected in this study. The healthy lung fibroblast cell was used as a control. Chitosan-coated MNPs (CS@MNPs) and antisense oligodeoxynucleotide of survivin gene were conjugated to MNPs to give Sur-MNPs. Fourier transform infrared spectroscopy was performed to confirm the conjunction of chitosan. The interactions of MNPs, CS@MNPs, and Sur-MNPs in BxPC-3 cells were observed, recorded and analyzed. The size, morphology, cell uptake, cytotoxicity and stability of those particles were assessed by transmission electron microscope, Prussian blue staining, MTT assay and agarose gel electrophoresis. The magnetic resonance signal intensities of pancreatic cells labeled with CS@MNPs and MNPs, and Sur-MNPs, were compared on T(2) -weighted images. The results demonstrated that the level of cellular uptake of CS@MNPs was higher than that of naked MNPs.  The Sur-MNPs had a suitable size (12 nm sized core), high stability, no cytotoxicity and good water dispersion. Sur-MNPs did not accumulate in healthy lung fibroblast cells, while being taken up by BxPC-3 cells. The Sur-MNPs in BxPC-3 cells could be visualized on T(2) -weighted images, which suggested that Sur-MNPs could be used to detect the expression of survivin gene. Thus, Sur-MNPs  may be a potential molecular imaging probe targeting survivin gene for early detection of pancreatic cancer cells. Copyright © 2012 John Wiley & Sons, Ltd.

----------------------------------------------------

[391]

TÍTULO / TITLE:  - Downregulation of TRAF2 Mediates NIK-Induced Pancreatic Cancer Cell Proliferation and Tumorigenicity.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e53676. doi: 10.1371/journal.pone.0053676. Epub 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053676

AUTORES / AUTHORS:  - Doppler H; Liou GY; Storz P

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, Florida, United States of America.

RESUMEN / SUMMARY:  - BACKGROUND: Increased levels of NF-kappaB are hallmarks of pancreatic ductal adenocarcinoma (PDAC) and both classical and alternative NF-kappaB activation pathways have been implicated. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that  activation of the alternative pathway is a source for the high basal NF-kappaB activity in PDAC cell lines. Increased activity of the p52/RelB NF-kappaB complex is mediated through stabilization and activation of NF-kappaB-inducing kinase (NIK). We identify proteasomal downregulation of TNF receptor-associated factor 2 (TRAF2) as a mechanism by which levels of active NIK are increased in PDAC cell lines. Such upregulation of NIK expression and activity levels relays to increased proliferation and anchorage-independent growth, but not migration or survival of PDAC cells. CONCLUSIONS/SIGNIFICANCE: Rapid growth is one characteristic of pancreatic cancer. Our data indicates that the TRAF2/NIK/NF-kappaB2 pathway regulates PDAC cell tumorigenicity and could be a valuable target for therapy of this cancer.

----------------------------------------------------

[392]

TÍTULO / TITLE:  - The impact of simultaneous liver resection for occult liver metastases of pancreatic adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastroenterol Res Pract. 2012;2012:939350. doi: 10.1155/2012/939350. Epub 2012 Nov 8.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/939350

AUTORES / AUTHORS:  - Klein F; Puhl G; Guckelberger O; Pelzer U; Pullankavumkal JR; Guel S; Neuhaus P; Bahra M

INSTITUCIÓN / INSTITUTION:  - Department of General, Visceral, and Transplantation Surgery, Charite Campus Virchow, Universitatsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

RESUMEN / SUMMARY:  - Backround. Pancreas resection is the only curative treatment for pancreatic adenocarcinoma. In the event of unexpected incidental liver metastases during operative exploration patients were traditionally referred to palliative treatment arms. With continuous progress in the surgical expertise simultaneous pancreas and liver resections seem technically feasible nowadays. The aim of this study therefore was to analyze the impact of synchronous liver-directed therapy on operative outcome and overall survival in patients with hepatic metastasized pancreatic adenocarcinoma (HMPA). Methods. 22 patients who underwent simultaneous pancreas resection and liver-directed therapy for HMPA between January 1, 2004 and January 1, 2009 were compared to 22 patients who underwent classic pancreas resection for nonmetastasized pancreatic adenocarcinoma (NMPA) in a matched pair  study design. Postoperative morbidity, preoperative, and operative data and overall survival were analyzed. Results. Overall survival was significantly decreased in the HMPA group. Postoperative morbidity and mortality and median operation time did not significantly differ between the groups. Conclusion. The results of our study showed that simultaneous pancreas resection and liver-directed therapy may safely be performed and may therefore be applied in individual patients with HMPA. However, a potential benefit of this radical surgical approach with regard to overall survival and/or quality of life remains  to be proven.

----------------------------------------------------

[393]

TÍTULO / TITLE:  - Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: the role of neutrophils and neutrophil-derived elastase.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Dev Immunol. 2012;2012:720768. doi: 10.1155/2012/720768. Epub 2012 Nov 20.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/720768

AUTORES / AUTHORS:  - Grosse-Steffen T; Giese T; Giese N; Longerich T; Schirmacher P; Hansch GM; Gaida MM

INSTITUCIÓN / INSTITUTION:  - Institut fur Immunologie, Universitat Heidelberg, Germany. t.grosse-steffen@web.de

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with fibrosis and a prominent inflammatory infiltrate in the desmoplastic stroma. Moreover, in  PDAC, an epithelial-to-mesenchymal transition (EMT) is observed. To explore a possible connection between the infiltrating cells, particularly the polymorphonuclear neutrophils (PMN) and the tumor cell transition, biopsies of patients with PDAC (n = 115) were analysed with regard to PMN infiltration and nuclear expression of beta-catenin and of ZEB1, well-established indicators of EMT. In biopsies with a dense PMN infiltrate, a nuclear accumulation of beta-catenin and of ZEB1 was observed. To address the question whether PMN could  induce EMT, they were isolated from healthy donors and were cocultivated with pancreatic tumor cells grown as monolayers. Rapid dyshesion of the tumor cells was seen, most likely due to an elastase-mediated degradation of E-cadherin. In parallel, the transcription factor TWIST was upregulated, beta-catenin translocated into the nucleus, ZEB1 appeared in the nucleus, and keratins were downregulated. EMT was also induced when the tumor cells were grown under conditions preventing attachment to the culture plates. Here, also in the absence of elastase, E-cadherin was downmodulated. PMN as well as prevention of adhesion  induced EMT also in liver cancer cell line. In conclusion, PMN via elastase induce EMT in vitro, most likely due to the loss of cell-to-cell contact. Because in pancreatic cancers the transition to a mesenchymal phenotype coincides with the PMN infiltrate, a contribution of the inflammatory response to the induction  of EMT and-by implication-to tumor progression is possible.

----------------------------------------------------

[394]

TÍTULO / TITLE:  - Mass Spectrometry-Based (GeLC-MS/MS) Comparative Proteomic Analysis of Endoscopically (ePFT) Collected Pancreatic and Gastroduodenal Fluids.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Gastroenterol. 2012 May 3;3:e14. doi: 10.1038/ctg.2012.7.

            ●● Enlace al texto completo (gratuito o de pago) 1038/ctg.2012.7

AUTORES / AUTHORS:  - Paulo JA; Kadiyala V; Banks PA; Steen H; Conwell DL

INSTITUCIÓN / INSTITUTION:  - 1] Department of Pathology, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA [2] Proteomics Center at Children’s Hospital Boston, Boston, Massachusetts, USA [3] Center for Pancreatic Disease, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

RESUMEN / SUMMARY:  - OBJECTIVES: The secretin-stimulated endoscopic pancreatic function test (ePFT) allows for the safe collection of gastroduodenal and pancreatic fluid from the duodenum. We test the hypothesis that these endoscopically collected fluids have  different proteomes. As such, we aim to show that the ePFT method can be used to  collect fluid enriched in pancreatic proteins to test for pancreatic function. METHODS: Gastroduodenal and pancreatic fluid were collected sequentially from chronic pancreatitis patients undergoing an ePFT. Proteins from each fluid type were extracted using previously published optimized methods and subjected to GeLC-MS/MS analysis for protein identification and bioinformatics analysis. RESULTS: Mass spectrometry analysis identified proteins that were exclusive in either gastroduodenal (46) or pancreatic fluid (234). Subsequent quantitative analysis revealed proteins that were differentially abundant with statistical significance. As expected, proteolytic enzymes and protease inhibitors were among the differentially detected proteins. The proteases pepsinogens and gastrin were  enriched in gastroduodenal fluid, while common pancreatic enzymes (e.g., aminopeptidase N, chymotrypsin C, elastase-3A, trypsin, and carboxypeptidase A1,  and elastase 2B) were found in greater abundance in pancreatic fluid. Similarly for protease inhibitors, members of the cystatin family were exclusive to gastroduodenal fluid, while serpins A11, B4, and D1 were exclusive to pancreatic  fluid. CONCLUSIONS: We have shown that ePFT collection coupled with mass spectrometry can be used to identify differentially detected proteins in gastroduodenal and pancreatic fluids. The data obtained using GeLC-MS/MS techniques provide further evidence supporting the feasibility of using ePFT-collected fluid to study specific diseases of the upper gastrointestinal tract, such as chronic pancreatitis.

----------------------------------------------------

[395]

TÍTULO / TITLE:  - Pancreatic cystic neoplasms: Predictors of malignant behavior and management.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Saudi J Gastroenterol. 2013 Jan;19(1):45-53. doi: 10.4103/1319-3767.105927.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1319-3767.105927

AUTORES / AUTHORS:  - Atef E; El Nakeeb A; El Hanafy E; El Hemaly M; Hamdy E; El-Geidie A

INSTITUCIÓN / INSTITUTION:  - Gastroenterology Surgical Center, Mansoura University, Egypt.

RESUMEN / SUMMARY:  - Background/Aim: Pancreatic cystic neoplasms are being increasingly identified with the widespread use of advanced imaging techniques. In the absence of a good  radiologic or pathologic test to preoperatively determine the dianosis, clinical  characteristics might be helpful. The objectives of this analysis were to define  the incidence and predictors of malignancy in pancreatic cysts. Patients and Methods: Patients with true pancreatic cysts who were treated at our institution  were included. Patients with documented pseudocysts were excluded. Demographic data, clinical manifestations, radiological, surgical, and pathological records of those patients were reviewed. Results: Eighty-one patients had true pancreatic cyst. The mean age was 47 +/- 15.5 years. There were 28.4% serous cystadenoma, 21% mucinous cystadenoma, 6.2% intraductal papillary tumors, 8.6% solid pseudopapillary tumors, 1.2% neuroendocrinal tumor, 3.7% ductal adenocarcinoma, and 30.9% mucinous cystadenocarcinoma. Malignancy was significantly associated with men (P = 0.04), older age (0.0001), cysts larger than 3 cm in diameter (P =  0.001), presence of solid component (P = 0.0001), and cyst wall thickening (P = 0.0001). The majority of patients with malignancy were symptomatic (26/28, 92.9%). The symptoms that correlated with malignancy included abdominal pain (P = 0.04) and weight loss (P = 0.0001). Surgical procedures were based on the location and extension of the lesion. Conclusion: The most common pancreatic cysts were serous and mucinous cysts. These tumors were more common in females. Old age, male gender, large tumor, presence of solid component, wall thickness, and presence of symptoms may predict malignancy in the cyst.

----------------------------------------------------

[396]

TÍTULO / TITLE:  - Concomitant intraductal papillary mucinous neoplasm and neuroendocrine tumor of the pancreas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):63-67. Epub 2012 Oct 3.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.952

AUTORES / AUTHORS:  - Ishida M; Shiomi H; Naka S; Tani T; Okabe H

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology;

RESUMEN / SUMMARY:  - Intraductal papillary mucinous neoplasm (IPMN) and neuroendocrine tumor (NET) of  the pancreas are rare tumors and their association is not expected to be frequent. However, certain studies have suggested that the concomitant occurence  of these tumors may be more frequent than previously thought. In the current study, we describe a case of concomitant occurrence of IPMN and NET of the pancreas and review the clinicopathological features of previously published cases and the current one. A 68-year-old female was incidentally found to have dilatation of the main pancreatic duct. A distal pancreatectomy was performed under the clinical diagnosis of IPMN. Histopathological analysis revealed concomitant IPMN (low-grade) and NET G1 of the pancreas. Review of the clinicopathological features of the 15 previously reported cases of concomitant IPMN and NET of the pancreas as well as the present one indicated that: i) this condition mainly affects middle-aged females; ii) the main symptom is abdominal or back pain, or no symptoms; iii) a hormone production symptom was observed in only one case; iv) the most common degree of dysplasia of IPMN is low grade; and  v) the size of the NET is not particularly large (average 15.1 mm), although the  clinical behavior is not always indolent (metastasis was observed in 3 cases). It is well known that IPMNs are associated with a high incidence of extrapancreatic  malignancies, including colorectal and gastric carcinomas. Concomitant pancreatic NET and extrapancreatic malignancies may occur, therefore, systemic surveillance  of extrapancreatic neoplasms and detection of concomitant NETs of the pancreas are necessary for patients with IPMN.

----------------------------------------------------

[397]

TÍTULO / TITLE:  - Superior efficacy of co-treatment with dual PI3K/mTOR inhibitor NVP-BEZ235 and pan-histone deacetylase inhibitor against human pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncotarget. 2012 Nov;3(11):1416-27.

AUTORES / AUTHORS:  - Venkannagari S; Fiskus W; Peth K; Atadja P; Hidalgo M; Maitra A; Bhalla KN

INSTITUCIÓN / INSTITUTION:  - The University of Kansas Cancer Center, Kansas City, KS, USA.

RESUMEN / SUMMARY:  - Genetic alterations activating K-RAS and PI3K/AKT signaling are also known to induce the activity of mTOR kinase through TORC1 and TORC2 complexes in human pancreatic ductal adenocarcinoma (PDAC). Here, we determined the effects of the dual PI3K and mTOR inhibitor, NVP-BEZ235 (BEZ235), and the pan-histone deacetylase inhibitor panobinostat (PS) against human PDAC cells. Treatment with  BEZ235 or PS inhibited cell cycle progression with induction of the cell cycle inhibitory proteins, p21waf1 and p27kip1. BEZ235 and PS also dose dependently induced loss of cell viability of the cultured PDAC cells, associated with depletion of phosphorylated (p) AKT, as well as of the TORC1 substrates 4EBP1 and p70S6 kinase. While inhibiting p-AKT, treatment with PS induced the levels of the pro-apoptotic proteins BIM and BAK. Co-treatment with BEZ235 and PS synergistically induced apoptosis of the cultured PDAC cells. This was accompanied by marked attenuation of the levels of p-AKT and Bcl-xL but induction of BIM. Although in vivo treatment with BEZ235 or PS reduced tumor growth, co-treatment with BEZ235 and PS was significantly more effective in controlling the xenograft growth of Panc1 PDAC cells in the nude mice. Furthermore, co-treatment with BEZ235 and PS more effectively blocked tumor growth of primary  PDAC heterotransplants (possessing K-RAS mutation and AKT2 amplification) subcutaneously implanted in the nude mice than each agent alone. These findings demonstrate superior activity and support further in vivo evaluation of combined  treatment with BEZ235 and PS against PDAC that possess heightened activity of RAS-RAF-ERK1/2 and PI3K-AKT-mTOR pathways.

----------------------------------------------------

[398]

TÍTULO / TITLE:  - MSH2 and CXCR4 involvement in malignant VIPoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Surg Oncol. 2012 Dec 11;10:264. doi: 10.1186/1477-7819-10-264.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-10-264

AUTORES / AUTHORS:  - Muller S; Kupka S; Konigsrainer I; Northoff H; Sotlar K; Bock T; Kandolf R; Traub F; Konigsrainer A; Zieker D

INSTITUCIÓN / INSTITUTION:  - Department of General, Visceral and Transplant Surgery, Tubingen, Germany. derek.zieker@med.uni-tuebingen.de.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Vasoactive intestinal polypeptide secreting tumors(VIPomas) are rare endocrine tumors of the pancreas with an estimated incidence of 0.1 per  million per year. The molecular mechanisms that mediate development of VIPomas are poorly investigated and require definition. METHODS: A genome- and gene expression analysis of specimens of a primary pancreatic VIPoma with hepatic metastases was performed. The primary tumor, the metastases, the corresponding healthy tissue of the liver, and the pancreas were compared with each other using oligonucleotide microarrays and loss of heterozygosity (LOH). RESULTS: The results revealed multiple LOH events and several differentially expressed genes.  Our finding of LOH and downregulation was conspicuous in the microarray analysis  for the mismatch repair gene MSH2 in the primary pancreatic VIPoma tumor, the hepatic metastasis but not in the corresponding healthy tissue. Further a strong  overexpression of the chemokine CXCR4 was detected in the hepatic metastases compared to its pancreatic primary. With a review of the literature we describe the molecular insights of metastatic development in VIPoma. CONCLUSION: In VIPoma, defects in the mismatch repair system especially in MSH2 may contribute to carcinogenesis, and increased CXCR4 may be associated with liver metastasis.

----------------------------------------------------

[399]

TÍTULO / TITLE:  - Solid serous cystic neoplasm of the pancreas with invasive growth.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Hepatobiliary Pancreat Sci. 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00534-012-0575-x

AUTORES / AUTHORS:  - Lee SD; Han SS; Hong EK

INSTITUCIÓN / INSTITUTION:  - Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Republic of Korea.

----------------------------------------------------

[400]

TÍTULO / TITLE:  - Frankincense essential oil prepared from hydrodistillation of Boswellia sacra gum resins induces human pancreatic cancer cell death in cultures and in a xenograft  murine model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Complement Altern Med. 2012 Dec 13;12:253. doi: 10.1186/1472-6882-12-253.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1472-6882-12-253

AUTORES / AUTHORS:  - Ni X; Suhail MM; Yang Q; Cao A; Fung KM; Postier RG; Woolley C; Young G; Zhang J; Lin HK

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, Long Hua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China. zjzzzq@sina.com.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Regardless of the availability of therapeutic options, the  overall 5-year survival for patients diagnosed with pancreatic cancer remains less than 5%. Gum resins from Boswellia species, also known as frankincense, have been used as a major ingredient in Ayurvedic and Chinese medicine to treat a variety of health-related conditions. Both frankincense chemical extracts and essential oil prepared from Boswellia species gum resins exhibit anti-neoplastic  activity, and have been investigated as potential anti-cancer agents. The goals of this study are to identify optimal condition for preparing frankincense essential oil that possesses potent anti-tumor activity, and to evaluate the activity in both cultured human pancreatic cancer cells and a xenograft mouse cancer model. METHODS: Boswellia sacra gum resins were hydrodistilled at 78 degrees C; and essential oil distillate fractions were collected at different durations (Fraction I at 0-2 h, Fraction II at 8-10 h, and Fraction III at 11-12  h). Hydrodistillation of the second half of gum resins was performed at 100 degrees C; and distillate was collected at 11-12 h (Fraction IV). Chemical compositions were identified by gas chromatography-mass spectrometry (GC-MS); and total boswellic acids contents were quantified by high-performance liquid chromatography (HPLC). Frankincense essential oil-modulated pancreatic tumor cell viability and cytotoxicity were determined by colorimetric assays. Levels of apoptotic markers, signaling molecules, and cell cycle regulators expression were characterized by Western blot analysis. A heterotopic (subcutaneous) human pancreatic cancer xenograft nude mouse model was used to evaluate anti-tumor capability of Fraction IV frankincense essential oil in vivo. Frankincense essential oil-induced tumor cytostatic and cytotoxic activities in animals were assessed by immunohistochemistry. RESULTS: Longer duration and higher temperature hydrodistillation produced more abundant high molecular weight compounds, including boswellic acids, in frankincense essential oil fraactions. Human pancreatic cancer cells were sensitive to Fractions III and IV (containing higher molecular weight compounds) treatment with suppressed cell viability and increased cell death. Essential oil activated the caspase-dependent apoptotic pathway, induced a rapid and transient activation of Akt and Erk1/2, and suppressed levels of cyclin D1 cdk4 expression in cultured pancreatic cancer cells. In addition, Boswellia sacra essential oil Fraction IV exhibited anti-proliferative and pro-apoptotic activities against pancreatic tumors in the  heterotopic xenograft mouse model. CONCLUSION: All fractions of frankincense essential oil from Boswellia sacra are capable of suppressing viability and inducing apoptosis of a panel of human pancreatic cancer cell lines. Potency of essential oil-suppressed tumor cell viability may be associated with the greater  abundance of high molecular weight compounds in Fractions III and IV. Although chemical component(s) responsible for tumor cell cytotoxicity remains undefined,  crude essential oil prepared from hydrodistillation of Boswellia sacra gum resins might be a useful alternative therapeutic agent for treating patients with pancreatic adenocarcinoma, an aggressive cancer with poor prognosis.

----------------------------------------------------

[401]

TÍTULO / TITLE:  - Sonic advance: CCN1 regulates sonic hedgehog in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cell Commun Signal. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12079-012-0187-x

AUTORES / AUTHORS:  - Leask A

INSTITUCIÓN / INSTITUTION:  - Department of Dentistry, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1, Andrew.Leask@schulich.uwo.ca.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer internationally. As the precise molecular pathways that regulate pancreatic cancer are incompletely understood, appropriate targets for drug intervention remain elusive. It is being increasingly appreciated that the cellular microenvironment plays an important role in driving tumor growth and metastasis.  CCN1, a member of the CCN family of secreted matricellular proteins, is overexpressed in pancreatic cancer, and may represent a novel target for therapy. Sonic hedgehog (SHh) is responsible for PDAC cell proliferation, epithelial-mesenchymal transition (EMT), maintenance of cancer stemness, migration, invasion, and metastatic growth; in a recent report, it was shown that CCN1 is a potent regulator of SHh expression via Notch-1. CCN1 activity was mediated, at least in part, through altering proteosome activity. These results suggest that CCN1 may be an ideal target for treating PDAC.

----------------------------------------------------

[402]

TÍTULO / TITLE:  - Association of diabetes and perineural invasion in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Med. 2012 Dec;1(3):357-62. doi: 10.1002/cam4.43. Epub 2012 Oct 30.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cam4.43

AUTORES / AUTHORS:  - Sahin IH; Shama MA; Tanaka M; Abbruzzese JL; Curley SA; Hassan M; Li D

INSTITUCIÓN / INSTITUTION:  - Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center Houston, Texas.

RESUMEN / SUMMARY:  - Diabetes and perineural invasion are frequently observed in pancreatic cancer. In this study, we tested possible relations between diabetes and perineural invasion in patients with resected pancreatic cancer. We conducted a retrospective study in 544 cases of resected pancreatic adenocarcinoma seen at the University of Texas MD Anderson Cancer Center during 1996-2011. Information on tumor characteristics, diabetes history, and survival time was collected by personal interview and medical record review. Patients with diabetes before or at the time of the pancreatic cancer diagnosis were considered diabetes only. Pearson chi(2)  test was used to compare categorical variables in diabetic and nondiabetic groups. Kaplan-Meier plot, log-rank test, and Cox proportional regression models  were applied in survival analysis. The prevalence of diabetes and perineural invasion was 26.5% and 86.9%, respectively, in this study population. Patients with diabetes had a significantly higher prevalence of perineural invasion (92.4%) than those without diabetes (85%) (P = 0.025, chi(2) test). Diabetes was  not associated with other pathological characteristics of the tumor, such as tumor size, lymphovascular invasion, tumor grade, lymph node metastasis, and resection margin status. Diabetic patients had a significantly lower frequency of abdominal pain (P = 0.01), but a slightly higher frequency of weight loss (P = 0.078) as early symptoms of their cancer. Both diabetes and perineural invasion were related to worse survival and increased risk of death after adjusting for tumor grade and margin and node status (P = 0.036 and 0.019, respectively). The observed associations of diabetes and perineural invasion as well as reduced frequency of pain as early symptom of pancreatic cancer support the hypothesis that diabetes may contribute to pancreatic progression via the mechanism of nerve damage.

----------------------------------------------------

[403]

TÍTULO / TITLE:  - Non-umbilical cutaneous metastasis of a pancreatic adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Jan 9;2013. pii: bcr2012007931. doi: 10.1136/bcr-2012-007931.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-007931

AUTORES / AUTHORS:  - Kaoutzanis C; Chang MC; Abdul Khalek FJ; Kreske E

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Saint Joseph Mercy Health System, Ann Arbor, Michigan, USA.

RESUMEN / SUMMARY:  - Pancreatic adenocarcinoma is one of the deadliest human malignancies with the majority of cases diagnosed late in the course of the disease. Cutaneous metastases originating from pancreatic cancer are rare. The most common site reported is the umbilicus. Non-umbilical cutaneous metastases are far less common with only a few cases reported in the literature. Our case involved a 43-year-old man with pancreatic carcinoma who was offered resection and a Whipple procedure was planned. Intraoperatively, the patient was found to have a widely metastatic  disease not seen on preoperative imaging. Postoperatively, cutaneous metastasis in the scalp was discovered. Although rare, the recognition of non-umbilical cutaneous metastases of pancreatic adenocarcinoma can be of value because they can not only detect an underlying tumour but also guide management.

----------------------------------------------------

[404]

TÍTULO / TITLE:  - Pedunculated insulinoma on the anterior border of the head of the pancreas: An unusual location to be aware of.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Diagn Interv Imaging. 2013 Jan 23. pii: S2211-5684(12)00174-X. doi: 10.1016/j.diii.2012.04.025.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.diii.2012.04.025

AUTORES / AUTHORS:  - Sebbag-Sfez D; Berrod JL; Palazzo L; Zins M

INSTITUCIÓN / INSTITUTION:  - Department of Radiology and Digestive Surgery, fondation hopital Saint-Joseph, 185, rue Raymond-Losserand, 75014 Paris, France. Electronic address: delphinesebbag@gmail.com.

----------------------------------------------------

[405]

TÍTULO / TITLE:  - Primary hepatic gastrinoma as an unusual manifestation of zollinger-ellison syndrome.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Gastroenterol. 2012 Sep;6(3):590-5. doi: 10.1159/000343157. Epub 2012 Sep 18.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000343157

AUTORES / AUTHORS:  - Naoe H; Iwasaki H; Kawasaki T; Ozaki T; Tsutsumi H; Okuda A; Konoe T; Nonaka K; Kaku E; Shono T; Yokomine K; Sakurai K; Iyama K; Hirota M; Sasaki Y

INSTITUCIÓN / INSTITUTION:  - Departments of Gastroenterology and Hepatology.

RESUMEN / SUMMARY:  - We report a rare case of primary hepatic gastrinoma. A 77-year-old woman exhibited continuous watery diarrhea for 8 months and weight loss. Bacterial cultures of the stools were negative and colonoscopy revealed no abnormalities. Esophagogastroduodenoscopy showed severe reflux esophagitis and multiple duodenal erosions. Computed tomography and magnetic resonance imaging detected two solid masses measuring <2 cm in diameter in the right lobe of the non-cirrhotic liver.  Microscopically, the tumor was consistent with neuroendocrine tumor (grade 2) with abundant gastrin-immunoreactive cells. Endoscopic ultrasound detected no other alternative primary source of an endocrine tumor. The serum gastrin levels  exceeded 40,000 pg/ml in the absence of H(2) receptor antagonist and proton pump  inhibitor administrations. Based on an arterial stimulation and venous sampling test, the patient was diagnosed as primary gastrinoma of the liver. Our findings  demonstrated the presence of Zollinger-Ellison syndrome in a patient who was subsequently cured by surgical resection of the liver tumors.

----------------------------------------------------

[406]

TÍTULO / TITLE:  - Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 22;12:614. doi: 10.1186/1471-2407-12-614.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-614

AUTORES / AUTHORS:  - Erdas E; Aste N; Pilloni L; Nicolosi A; Licheri S; Cappai A; Mastinu M; Cetani F; Pardi E; Mariotti S; Pomata M

INSTITUCIÓN / INSTITUTION:  - General Surgery Unit, Department of Surgical Sciences, San Giovanni di Dio Hospital, University of Cagliari, Cagliari, Italy. enricoerdas@medicina.unica.it.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is  commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case  of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in  which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. CASE PRESENTATION: The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight  loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations,  functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition.  Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation,  the patient is well and shows no signs or symptoms of recurrence. CONCLUSIONS: Despite well-defined diagnostic criteria and guidelines, diagnosis of MEN1 can still be challenging. When diagnosis is doubtful, appropriate management may be difficult to establish.

----------------------------------------------------

[407]

TÍTULO / TITLE:  - Microenvironment elements involved in the development of pancreatic cancer tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gastroenterol Res Pract. 2012;2012:585674. doi: 10.1155/2012/585674. Epub 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/585674

AUTORES / AUTHORS:  - Gardian K; Janczewska S; Durlik M

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Research and Transplantology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland.

RESUMEN / SUMMARY:  - Introduction. In spite of intensive research during many years, pancreatic adenocarcinoma remains one of the deadliest cancers. The surgical intervention remains main possibility of treatment because chemotherapy and radiotherapy has a minimal impact on long-term survival. We are still looking for the weak points of this devastating disease. Materials and Methods. Pancreatic tumor tissue samples  were collected from 36 patients. Immunohistochemistry staining was used to evaluate expression of growth factors and immune infiltrates. Activity of MMP2 and MMP9 was assessed by gelatin zymography on 7.5% SDS-PAGE gel with 0.1% gelatin. Results. All growth factors were strongly expressed in pancreatic tumor  tissue. We found that level of expression of c-Met receptor was higher for G3 tumors than for G2 tumors. Also we found that active MMP2 was present at all stages of tumor while active MMP9 just at more advanced tumors. Abundant immune cells infiltration was distinctive for tumor tissue, especially macrophages were  infiltrating tumor tissue. We found that amount of macrophages was associated with lymph nodes metastases. Conclusion. In our research we demonstrated that among many factors influencing tumor microenvironment c-Met receptor, infiltrating macrophages and MMP2 have significant influence on development and invasion of pancreatic cancer.

----------------------------------------------------

[408]

TÍTULO / TITLE:  - B Cell Activating Factor of the Tumor Necrosis Factor Family (BAFF) Behaves as an Acute Phase Reactant in Acute Pancreatitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54297. doi: 10.1371/journal.pone.0054297. Epub 2013 Jan 14.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054297

AUTORES / AUTHORS:  - Pongratz G; Hochrinner H; Straub RH; Lang S; Brunnler T

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

RESUMEN / SUMMARY:  - OBJECTIVE: To determine if B cell activating factor of the tumor necrosis factor  family (BAFF) acts as an acute phase reactant and predicts severity of acute pancreatitis. METHODS: 40 patients with acute pancreatitis were included in this  single center cohort pilot study. Whole blood and serum was analyzed on day of admission and nine consecutive days for BAFF, c-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and leucocyte numbers. Different severity Scores (Ranson, APACHE II, SAPS II, SAPS III) and the clinical course of the patient (treatment, duration of stay, duration ICU) were recorded. RESULTS: Serum BAFF correlates with CRP, an established marker of severity in acute pancreatitis at day of admission with a timecourse profil similar to IL-6 over the first nine days. Serum BAFF increases with Ranson score (Kruskal-Wallis: Chi2 = 10.8; p = 0.03) similar to CRP (Kruskal-Wallis: Chi2 = 9.4; p = 0.05 ). Serum BAFF, IL-6, and CRP levels are elevated in patients that need intensive care for  more than seven days and in patients with complicated necrotizing pancreatitis. Discriminant analysis and receiver operator characteristics show that CRP (wilks-lambda = 0.549; ROC: AUC 0.948) and BAFF (wilks-lambda = 0.907; ROC: AUC 0.843) serum levels at day of admission best predict severe necrotizing pancreatitis or death, outperforming IL-6, PCT, and number of leucocytes. CONCLUSION: This study establishes for the first time BAFF as an acute phase reactant with predictive value for the course of acute pancreatitis. BAFF outperforms established markers in acute pancreatitis, like IL-6 and PCT underscoring the important role of BAFF in the acute inflammatory response.

----------------------------------------------------

[409]

TÍTULO / TITLE:  - Notch1 Is Not Required for Acinar-to-Ductal Metaplasia in a Model of Kras-Induced Pancreatic Ductal Adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52133. doi: 10.1371/journal.pone.0052133. Epub 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052133

AUTORES / AUTHORS:  - Avila JL; Troutman S; Durham A; Kissil JL

INSTITUCIÓN / INSTITUTION:  - Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma is believed to arise from precursor lesions termed pancreatic intraepithelial neoplasia (PanIN). Mouse models have demonstrated that targeted expression of activated K-ras to mature acinar cells in the pancreas induces the spontaneous development of PanIN lesions; implying acinar-to-ductal metaplasia (ADM) is a key event in this process. Recent studies  suggest Notch signaling is a key regulator of ADM. To assess if Notch1 is required for K-ras driven ADM we employed both an in vivo mouse model and in vitro explant culture system, in which an oncogenic allele of K-ras is activated  and Notch1 is deleted simultaneously in acinar cells. Our results demonstrate that oncogenic K-ras is sufficient to drive ADM both in vitro and in vivo but that loss of Notch1 has a minimal effect on this process. Interestingly, while loss of Notch1 in vivo does not affect the severity of PanIN lesions observed, the overall numbers of lesions were greater in mice with deleted Notch1. This suggests Notch1 deletion renders acinar cells more susceptible to formation of K-ras-induced PanINs.

----------------------------------------------------

[410]

TÍTULO / TITLE:  - Immunohistochemical Staining of B7-H1 (PD-L1) on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Vis Exp. 2013 Jan 3;(71). pii: 4059. doi: 10.3791/4059.

            ●● Enlace al texto completo (gratuito o de pago) 3791/4059

AUTORES / AUTHORS:  - Bigelow E; Bever KM; Xu H; Yager A; Wu A; Taube J; Chen L; Jaffee EM; Anders RA; Zheng L

INSTITUCIÓN / INSTITUTION:  - The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine.

RESUMEN / SUMMARY:  - B7-H1/PD-L1, a member of the B7 family of immune-regulatory cell-surface proteins, plays an important role in the negative regulation of cell-mediated immune responses through its interaction with its receptor, programmed death-1 (PD-1) (1,2). Overexpression of B7-H1 by tumor cells has been noted in a number of human cancers, including melanoma, glioblastoma, and carcinomas of the lung, breast, colon, ovary, and renal cells, and has been shown to impair anti-tumor T-cell immunity(3-8). Recently, B7-H1 expression by pancreatic adenocarcinoma tissues has been identified as a potential prognostic marker(9,10). Additionally, blockade of B7-H1 in a mouse model of pancreatic cancer has been shown to produce an anti-tumor response(11). These data suggest the importance of B7-H1 as a potential therapeutic target. Anti-B7-H1 blockade antibodies are therefore being  tested in clinical trials for multiple human solid tumors including melanoma and  cancers of lung, colon, kidney, stomach and pancreas(12). In order to eventually  be able to identify the patients who will benefit from B7-H1 targeting therapies, it is critical to investigate the correlation between expression and localization of B7-H1 and patient response to treatment with B7-H1 blockade antibodies. Examining the expression of B7-H1 in human pancreatic adenocarcinoma tissues through immunohistochemistry will give a better understanding of how this co-inhibitory signaling molecule contributes to the suppression of antitumor immunity in the tumor’s microenvironment. The anti-B7-H1 monoclonal antibody (clone 5H1) developed by Chen and coworkers has been shown to produce reliable staining results in cryosections of multiple types of human neoplastic tissues(4,8), but staining on paraffin-embedded slides had been a challenge until recently(13-18). We have developed the B7-H1 staining protocol for paraffin-embedded slides of pancreatic adenocarcinoma tissues. The B7-H1 staining protocol described here produces consistent membranous and cytoplasmic staining of B7-H1 with little background.

----------------------------------------------------

[411]

TÍTULO / TITLE:  - Metastatic pancreatic carcinoma to the orbital apex presenting as a superior divisional third cranial nerve palsy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Ophthalmol. 2012;6:1941-3. doi: 10.2147/OPTH.S30208. Epub 2012 Nov 23.

            ●● Enlace al texto completo (gratuito o de pago) 2147/OPTH.S30208

AUTORES / AUTHORS:  - Pecen PE; Ramey NA; Richard MJ; Bhatti MT

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA;

RESUMEN / SUMMARY:  - Metastatic tumors to the orbit are rare, especially from a primary pancreatic carcinoma. A 59-year-old man presented with 4 weeks of right eye pain and eyelid  swelling. There was right upper eyelid ptosis associated with a right supraduction deficit consistent with a superior divisional third cranial nerve (CN III) palsy. Magnetic resonance imaging revealed a right orbital apex lesion.  A right orbital exenteration was performed for intractable and severe pain. Surgical pathology demonstrated a poorly differentiated carcinoma that was ultimately felt to be derived from the pancreas. In this report, we describe the  clinical and neurological imaging findings of a superior divisional CN III palsy  as the presenting manifestation of a presumed metastatic pancreatic carcinoma to  the orbital apex, and review the neuroanatomy of CN III with particular emphasis  on the anatomical bifurcation of the nerve into a superior and inferior division.

----------------------------------------------------

[412]

TÍTULO / TITLE:  - Huge cystic lymphangioma of the pancreas mimicking pancreatic cystic neoplasm.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Report Med. 2012;2012:951358. doi: 10.1155/2012/951358. Epub 2012 Nov 6.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/951358

AUTORES / AUTHORS:  - Dalla Bona E; Beltrame V; Blandamura S; Liessi F; Sperti C

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Oncology, and Gastroenterology, University of Padua, 35128 Padua, Italy.

RESUMEN / SUMMARY:  - Lymphangiomas of the pancreas are very rare benign tumors of lymphatic origin, accounting for less than 1% of these neoplasms. We report a case of a 55-year-old woman who presented with a palpable mass in the left abdomen. Abdominal sonography and computed tomography showed a lobulated, hypodense mass extending from the left diaphragm to the pelvis, measuring 10 x 25 cm. A preoperative diagnosis of mucinous cystadenoma of the pancreas was suggested and the patient underwent laparotomy. Distal pancreatectomy with splenectomy was performed, encompassing a segment of descending colon because of close relationship to the mass. The cystic mass was histologically diagnosed as lymphangioma of the pancreas. The patient is well and free of disease 12 months after surgery. Pancreatic lymphangioma should be kept in mind when a huge, multiloculated mass is encountered in the abdomen, especially in adult women. Although lymphangioma is considered a benign tumor, involvement of adjacent organs sometimes occurs and extended resection is required to obtain a radical treatment.

----------------------------------------------------

[413]

TÍTULO / TITLE:  - EZH2 is required for breast and pancreatic cancer stem cell maintenance and can be used as a functional cancer stem cell reporter.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stem Cells. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://stemcells.alphamedpress.org/ 

            ●● Cita: Stem Cells: <> Transl Med. 2013 Jan;2(1):43-52. doi: 10.5966/sctm.2012-0036. Epub 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 5966/sctm.2012-0036

AUTORES / AUTHORS:  - van Vlerken LE; Kiefer CM; Morehouse C; Li Y; Groves C; Wilson SD; Yao Y; Hollingsworth RE; Hurt EM

INSTITUCIÓN / INSTITUTION:  - Department of Oncology Research, Medlmmune, LLC, MD, USA.

RESUMEN / SUMMARY:  - Although cancer is largely seen as a disease stemming from genetic mutations, evidence has implicated epigenetic regulation of gene expression as a driving force for tumorigenesis. Epigenetic regulation by histone modification, specifically through polycomb group (PcG) proteins such as EZH2 and BMI-1, is a major driver in stem cell biology and is found to be correlated with poor prognosis in many tumor types. This suggests a role for PcG proteins in cancer stem cells (CSCs). We hypothesized that epigenetic modification by EZH2, specifically, helps maintain the CSC phenotype and that in turn this epigenetic modifier can be used as a reporter for CSC activity in an in vitro high-throughput screening assay. CSCs isolated from pancreatic and breast cancer  lines had elevated EZH2 levels over non-CSCs. Moreover, EZH2 knockdown by RNA interference significantly reduced the frequency of CSCs in all models tested, confirming the role of EZH2 in maintenance of the CSC population. Interestingly,  genes affected by EZH2 loss, and therefore CSC loss, were inversely correlated with genes identified by CSC enrichment, further supporting the function of EZH2  CSC regulation. We translated these results into a novel assay whereby elevated EZH2 staining was used as a reporter for CSCs. Data confirmed that this assay could effectively measure changes, both inhibition and enrichment, in the CSC population, providing a novel approach to look at CSC activity. This assay provides a unique, rapid way to facilitate CSC screening across several tumor types to aid in further CSC-related research.

----------------------------------------------------

[414]

TÍTULO / TITLE:  - Metastatic leiomyosarcoma of the intrapancreatic bile duct.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Korean Surg Soc. 2013 Jan;84(1):66-9. doi: 10.4174/jkss.2013.84.1.66. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 4174/jkss.2013.84.1.66

AUTORES / AUTHORS:  - Perysinakis I; Katopodi A; Avlonitis S; Georgiadou D; Choreftaki T; Christopoulos G; Margaris I

INSTITUCIÓN / INSTITUTION:  - 3rd Surgical Department, George Gennimatas General Hospital of Athens, Athens, Greece.

RESUMEN / SUMMARY:  - We report the case of a patient with a history of surgically treated pulmonary leiomyosarcoma, presenting with recurrent acute cholangitis and metastatic leiomyosarcoma of the common bile duct. Preoperative examinations had revealed a  high grade malignant neoplasm and bilateral lung metastases. The patient underwent pylorus-preserving pancreaticoduodenectomy and survived for 5.5 years after the first diagnosis.

----------------------------------------------------

[415]

TÍTULO / TITLE:  - Probing pathways for pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Discov. 2013 Jan;3(1):6. doi: 10.1158/2159-8290.CD-NB2012-142. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-NB2012-142

RESUMEN / SUMMARY:  - Analysis of 99 pancreatic cancers revealed 2,016 mutations, including mutated genes involved in DNA damage repair, modification of chromatin, and axon guidance.

----------------------------------------------------

[416]

TÍTULO / TITLE:  - Immunotherapy updates in pancreatic cancer: are we there yet?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ther Adv Med Oncol. 2013 Jan;5(1):81-9. doi: 10.1177/1758834012462463.

            ●● Enlace al texto completo (gratuito o de pago) 1177_1758834012462463 [pii

            ●● Enlace al texto completo (gratuito o de pago) 1177/1758834012462463

AUTORES / AUTHORS:  - Gunturu KS; Rossi GR; Saif MW

INSTITUCIÓN / INSTITUTION:  - Division of Hematology/Onocology and Department of Medicine and Cancer Center, Tufts Medical Center, Boston, MA, USA.

RESUMEN / SUMMARY:  - Pancreatic cancer is a lethal disease and remains one of the most resistant cancers to traditional therapies. Historically, chemotherapy or radiotherapy did  not provide meaningful survival benefit in advanced pancreatic cancer. Gemcitabine and recently FOLFIRINOX (5-flourouracil, leucovorin, oxaliplatin and  irinotecan) have provided some limited survival advantage in advanced pancreatic  cancer. Targeted agents in combination with gemcitabine had not shown significant improvement in the survival. Current therapies for pancreatic cancer have their limitations; thus, we are in dire need of newer treatment options. Immunotherapy  in pancreatic cancer works by recruiting and activating T cells that recognize tumor-specific antigens which is a different mechanism compared with chemotherapy and radiotherapy. Preclinical models have shown that immunotherapy and targeted therapies like vascular endothelial growth factor and epidermal growth factor inhibitors work synergistically. Hence, new immunotherapy and targeted therapies  represent a viable option for pancreatic cancer. In this article, we review the vaccine therapy for pancreatic cancer.

----------------------------------------------------

[417]

TÍTULO / TITLE:  - Bufalin enhances the antitumor effect of gemcitabine in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Oct;4(4):792-798. Epub 2012 Jul 2.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.783

AUTORES / AUTHORS:  - Chen Y; Guo Q; Zhang B; Kang M; Xie Q; Wu Y

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang  University, Hangzhou, Zhejiang 310009, P.R. China.

RESUMEN / SUMMARY:  - Bufalin, an active component of the Chinese medicine chan’su, has been reported to have an inhibitory effect on the growth of various types of cancer cells. In the present study, we investigated whether gemcitabine combined with bufalin enhanced the antitumor efficacy in pancreatic cancer. Three pancreatic cancer cell lines (Bxpc-3, Mia PaCa-2 and Panc-1) were treated with gemcitabine and/or bufalin in vitro. The combination treatment demonstrated greater inhibition of cellular growth and apoptosis. The activity of apoptosis signal-regulating kinase 1 (ASK1)/JNK was upregulated in gemcitabine-induced apoptosis when combined with  bufalin. We also observed that tumor growth was significantly inhibited by the combination therapy in a tumor-bearing mouse model, and upregulation of ASK1 activity was validated by immunohistochemical staining. These results suggest that bufalin may be a potential chemotherapeutic agent for pancreatic cancer, which could enhance the antitumor efficacy of gemcitabine when used in combination, possibly through the activation of ASK1/JNK.

----------------------------------------------------