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Artículos originales (todos) *** Original articles (all)

Pancreatic cancer.

February - March 2013

 

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[1]

TÍTULO / TITLE:  - Case records of the Massachusetts General Hospital. Case 6-2013. A 54-year-old man with recurrent diarrhea.

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

REVISTA / JOURNAL:  - N Engl J Med. 2013 Feb 21;368(8):757-65. doi: 10.1056/NEJMcpc1208149.

            ●● Enlace al texto completo (gratuito o de pago) 1056/NEJMcpc1208149

AUTORES / AUTHORS:  - Simmons LH; Guimaraes AR; Zukerberg LR

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Massachusetts General Hospital, Boston, USA.

 

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[2]

TÍTULO / TITLE:  - Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer.

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

REVISTA / JOURNAL:  - Ann Oncol. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt066

AUTORES / AUTHORS:  - Wolpin BM; O’Reilly EM; Ko YJ; Blaszkowsky LS; Rarick M; Rocha-Lima CM; Ritch P; Chan E; Spratlin J; Macarulla T; McWhirter E; Pezet D; Lichinitser M; Roman L; Hartford A; Morrison K; Jackson L; Vincent M; Reyno L; Hidalgo M

INSTITUCIÓN / INSTITUTION:  - Dana-Farber Cancer Institute, Boston.

RESUMEN / SUMMARY:  - BackgroundWe evaluated AGS-1C4D4, a fully human monoclonal antibody to prostate stem cell antigen (PSCA), with gemcitabine in a randomized, phase II study of metastatic pancreatic cancer.Patients and methodsPatients with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and previously untreated, metastatic pancreatic adenocarcinoma were randomly assigned 1:2 to gemcitabine (1000 mg/m2 weekly seven times, 1 week rest, weekly three times q4weeks) or gemcitabine plus AGS-1C4D4 (48 mg/kg loading dose, then 24 mg/kg q3weeks IV). The primary end point was 6-month survival rate (SR). Archived tumor samples were collected for pre-planned analyses by PSCA expression.ResultsBetween April 2009 and May 2010, 196 patients were randomly assigned to gemcitabine (n =  63) or gemcitabine plus AGS-1C4D4 (n = 133). The 6-month SR was 44.4% (95% CI, 31.9-57.5) in the gemcitabine arm and 60.9% (95% CI, 52.1-69.2) in the gemcitabine plus AGS-1C4D4 arm (P = 0.03), while the median survival was 5.5 versus 7.6 months and the response rate was 13.1% versus 21.6% in the two arms, respectively. The 6-month SR was 57.1% in the gemcitabine arm versus 79.5% in the gemcitabine plus AGS-1C4D4 arm among the PSCA-positive subgroup and 31.6% versus  46.2% among the PSCA-negative subgroup.ConclusionsThis randomized, phase II study achieved its primary end point, demonstrating an improved 6-month SR with addition of AGS-1C4D4 to gemcitabine among patients with previously untreated, metastatic pancreatic adenocarcinoma.ClinicalTrials.gov identifier: NCT00902291.

 

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[3]

TÍTULO / TITLE:  - Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway.

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

REVISTA / JOURNAL:  - Nature. 2013 Apr 4;496(7443):101-5. doi: 10.1038/nature12040. Epub 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nature12040

AUTORES / AUTHORS:  - Son J; Lyssiotis CA; Ying H; Wang X; Hua S; Ligorio M; Perera RM; Ferrone CR; Mullarky E; Shyh-Chang N; Kang Y; Fleming JB; Bardeesy N; Asara JM; Haigis MC; DePinho RA; Cantley LC; Kimmelman AC

INSTITUCIÓN / INSTITUTION:  - Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

RESUMEN / SUMMARY:  - Cancer cells have metabolic dependencies that distinguish them from their normal  counterparts. Among these dependencies is an increased use of the amino acid glutamine to fuel anabolic processes. Indeed, the spectrum of glutamine-dependent tumours and the mechanisms whereby glutamine supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma  (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate dehydrogenase (GLUD1) to convert glutamine-derived glutamate into alpha-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into  malate and then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumours.

 

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[4]

TÍTULO / TITLE:  - Dormant Cancer Cells Contribute to Residual Disease in a Model of Reversible Pancreatic Cancer.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Mar 15;73(6):1821-1830. Epub 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2067

AUTORES / AUTHORS:  - Lin WC; Rajbhandari N; Liu C; Sakamoto K; Zhang Q; Triplett AA; Batra SK; Opavsky R; Felsher DW; Dimaio DJ; Hollingsworth MA; Morris JP 4th; Hebrok M; Witkiewicz AK; Brody JR; Rui H; Wagner KU

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Eppley Institute for Research in Cancer and Allied Diseases; Departments of Biochemistry and Molecular Biology and Pathology and Microbiology, University of Nebraska Medical Center, Nebraska Medical Center, Omaha; Departments of Cancer Biology, Pathology, and Surgery, Thomas Jefferson University, Philadelphia, Philadelphia; Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford; and Diabetes Center, Department of Medicine, University of California, San Francisco, California.

RESUMEN / SUMMARY:  - The initiation and progression of pancreatic ductal adenocarcinoma (PDAC) is governed by a series of genetic and epigenetic changes, but it is still unknown whether these alterations are required for the maintenance of primary and metastatic PDAC. We show here that the c-Myc oncogene is upregulated throughout the entire process of neoplastic progression in human PDAC and in genetically engineered mice that express mutant Kras. To experimentally address whether c-Myc is essential for the growth and survival of cancer cells, we developed a novel mouse model that allows a temporally and spatially controlled expression of this  oncogene in pancreatic progenitors and derived lineages of the exocrine pancreas. Unlike previous reports, upregulation of c-Myc was sufficient to induce the formation of adenocarcinomas after a short latency without additional genetic manipulation of cell survival pathways. Deficiency in Cdkn2a increased the rate of metastasis but had no effect on tumor latency or c-Myc-mediated cancer maintenance. Despite a macroscopically complete regression of primary, metastatic, and transplantable tumors following the ablation of c-Myc, some cancer cells remained dormant. A significant number of these residual neoplastic  cells expressed cancer stem cell markers, and re-expression of exogenous c-Myc in these cells led to rapid cancer recurrence. Collectively, the results of this study suggest that c-Myc plays a significant role in the progression and maintenance of PDAC, but besides targeting this oncogene or its downstream effectors, additional therapeutic strategies are necessary to eradicate residual  cancer cells to prevent disease recurrence. Cancer Res; 73(6); 1821-30. ©2012 AACR.

 

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[5]

TÍTULO / TITLE:  - Immunohistochemically Detected Expression of 3 Major Genes (CDKN2A/p16, TP53, and SMAD4/DPC4) Strongly Predicts Survival in Patients With Resectable Pancreatic Cancer.

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

REVISTA / JOURNAL:  - Ann Surg. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e3182827a65

AUTORES / AUTHORS:  - Oshima M; Okano K; Muraki S; Haba R; Maeba T; Suzuki Y; Yachida S

INSTITUCIÓN / INSTITUTION:  - *Departments of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan daggerDepartment of Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan double daggerDepartment of Laboratory Medicine,  Social Insurance Ritsurin Hospital, Takamatsu, Kagawa, Japan section signDepartment of Surgery, Social Insurance Ritsurin Hospital, Takamatsu, Kagawa, Japan paragraph signDivision of Refractory Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.

RESUMEN / SUMMARY:  - OBJECTIVE:: The goal of this retrospective study was to clarify the clinical implications of the status of the 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4). BACKGROUND:: Recent whole-exome sequencing had shown that the landscape of the pancreatic ductal adenocarcinoma (PDAC) genome is notable for 4  frequently mutated genes (KRAS, TP53, CDKN2A/p16, and SMAD4/DPC4). METHODS:: We determined immunohistochemically the status of TP53, CDKN2A/p16, and SMAD4/DPC4 among the 4 genes because the KRAS gene is mutated in virtually all PDAC patients, and analyzed relationships with clinicopathological findings, including survival and patterns of disease progression, in 106 patients with PDAC undergoing radical surgery. RESULTS:: Abnormal immunolabeling of p53 was detected in 81.1% of PDACs and was significantly associated with tumor dedifferentiation (P = 0.022) and the presence of locoregional recurrence (P = 0.020). Loss of p16  and Smad4/Dpc4 immunolabeling was identified in 67.0% and 60.4%, respectively. Loss of p16 immunolabeling was associated with lymphatic invasion (P = 0.012) and postoperative widespread metastases (P < 0.001). A significant correlation was found between Smad4/Dpc4 immunolabeling and tumor size (P = 0.006), lymphatic invasion (P = 0.033), and lymph node metastasis (P = 0.006). Interestingly, all of the 6 patients demonstrating 5-year survival had intact SMAD4/DPC4. Kaplan-Meier survival analysis showed that lymph node metastasis (P = 0.001), lymphatic invasion (P = 0.008), the tumor (T) factor (T3 vs. T1/T2, P = 0.004), loss of p16 immunolabeling (P = 0.029), and loss of Smad4/Dpc4 immunolabeling (P  < 0.001) were significantly associated with shorter overall survival. Multivariate analysis revealed that loss of Smad4/Dpc4 immunolabeling was an independent and significant poor prognostic factor for overall and disease-free survival. On analysis of combinations of the status of these 3 genes, increasing  number of alterations reflected poorer survival. CONCLUSIONS:: Genetic alterations of these 3 genes and their accumulation are strongly associated with  malignant behavior of PDAC. Their immunohistochemical assessment at the time of diagnosis may provide a new prognostic tool, assisting in deciding optimal therapeutic strategies for patients.

 

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[6]

TÍTULO / TITLE:  - Circulating tumor cells in pancreatic cancer patients: Methods of detection and clinical implications.

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

REVISTA / JOURNAL:  - Int J Cancer. 2013 Feb 28. doi: 10.1002/ijc.28134.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28134

AUTORES / AUTHORS:  - Tjensvoll K; Nordgard O; Smaaland R

INSTITUCIÓN / INSTITUTION:  - Department of Haematology and Oncology, Stavanger University Hospital, N-4068, Stavanger, Norway.

RESUMEN / SUMMARY:  - The poor prognosis of pancreatic cancer patients is associated with the frequent  and early dissemination of the disease, as well as late detection due to unspecific and late symptoms from the primary tumor. Pancreatic cancers frequently spread to the liver, lung and skeletal system, suggesting that pancreatic tumor cells must be able to intravasate and travel through the circulation to distant organs. Circulating tumor cells (CTCs) are tumor cells that have acquired the ability to enter the circulatory system; this cell population is ultimately responsible for the development of metastases in distant organs. Clinical studies have revealed that the presence of CTCs in blood is correlated with disease progression for other cancers, such as breast, colorectal and prostate cancer. However, as CTCs are extremely rare, both enrichment and sensitive methods of detection are required for their enumeration. This review highlights various enrichment procedures and methods for the detection of CTCs. Furthermore, we systematically review previously reported studies of the clinical relevance of CTC detection in pancreatic cancer patients. There is evidence that  the presence of CTCs also correlates with an unfavorable outcome in pancreatic cancer patients. However, technical/methodological issues may explain why some studies only show a trend toward an association between CTC detection and disease progression. Larger studies, as well as characterization of the CTC population, are required to achieve further insight into the clinical implications of CTC detection in pancreatic cancer patients.

 

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[7]

TÍTULO / TITLE:  - Whole blood interferon-gamma levels predict the therapeutic effects of adoptive T-cell therapy in patients with advanced pancreatic cancer.

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

REVISTA / JOURNAL:  - Int J Cancer. 2013 Feb 19. doi: 10.1002/ijc.28117.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28117

AUTORES / AUTHORS:  - Ishikawa T; Kokura S; Sakamoto N; Okayama T; Endo M; Tsuchiya R; Okajima M; Matsuyama T; Adachi S; Kamada K; Katada K; Uchiyama K; Handa O; Takagi T; Yagi N; Ando T; Uno K; Naito Y; Yoshikawa T

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Cancer ImmunoCell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

RESUMEN / SUMMARY:  - A core challenge in administering immune-based treatments for cancer is the establishment of easily accessible immunological assays that can predict patients’ clinical responses to immunotherapy. In this study, our aim was to predict the therapeutic effects of adoptive T-cell therapy in patients with advanced pancreatic cancer. To do this, we evaluated whole blood cytokine levels  and peripheral regulatory T cells (Tregs) in 46 patients with unresectable or recurrent pancreatic cancer who received adoptive T-cell therapy at 2-week intervals. To test immune function, venous blood was obtained from patients before the start of therapy and 2 weeks after the 4th treatment. Whole blood interferon (IFN)-alpha levels (after stimulation with the Sendai virus) were evaluated, as well as the levels of 9 cytokines stimulated with phytohemagglutinin [interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12(p70), IL-13, tumor necrosis factor-alpha, IFN-gamma, and granulocyte-monocyte colony-stimulating factor]. Peripheral Tregs were analyzed by flow cytometry. Using the obtained data, we then observed the relationship between these immunological parameters and clinical outcome of patients. We found that the whole blood production of IFN-gamma, IL-2, IL-4, IL-5 and IL-13 significantly increased after adoptive T-cell therapy, whereas the number of peripheral Tregs did not change. Multivariate Cox proportional hazards analyses indicated that the number of peripheral Tregs before receiving adoptive T-cell therapy and the change in IFN-gamma levels after adoptive T-cell therapy were independent variables predicting overall survival. The findings of this study indicate that the assay of whole blood IFN-gamma production offers promise for evaluating the clinical response of patients to cancer immunotherapy.

 

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[8]

TÍTULO / TITLE:  - Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial.

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

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Mar;71(3):765-75. doi: 10.1007/s00280-013-2070-8. Epub 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2070-8

AUTORES / AUTHORS:  - Welsh JL; Wagner BA; van’t Erve TJ; Zehr PS; Berg DJ; Halfdanarson TR; Yee NS; Bodeker KL; Du J; Roberts LJ 2nd; Drisko J; Levine M; Buettner GR; Cullen JJ

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, 1528 JCP-UIHC, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Treatment for pancreatic cancer with pharmacological ascorbate (ascorbic acid, vitamin C) decreases tumor progression in preclinical models. A phase I clinical trial was performed to establish safety and tolerability of pharmacological ascorbate combined with gemcitabine in patients with biopsy-proven stage IV pancreatic adenocarcinoma. DESIGN: Nine subjects received  twice-weekly intravenous ascorbate (15-125 g) employing Simon’s accelerated titration design to achieve a targeted post-infusion plasma level of >/=350 mg/dL (>/=20 mM). Subjects received concurrent gemcitabine. Disease burden, weight, performance status, hematologic and metabolic laboratories, time to progression and overall survival were monitored. RESULTS: Mean plasma ascorbate trough levels were significantly higher than baseline (1.46 +/- 0.02 vs. 0.78 +/- 0.09 mg/dL, i.e., 83 vs. 44 muM, p < 0.001). Adverse events attributable to the drug combination were rare and included diarrhea (n = 4) and dry mouth (n = 6). Dose-limiting criteria were not met for this study. Mean survival of subjects completing at least two cycles (8 weeks) of therapy was 13 +/- 2 months. CONCLUSIONS: Data suggest pharmacologic ascorbate administered concurrently with  gemcitabine is well tolerated. Initial data from this small sampling suggest some efficacy. Further studies powered to determine efficacy should be conducted.

 

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[9]

TÍTULO / TITLE:  - Pancreatic cancer associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-4601

AUTORES / AUTHORS:  - Mace TA; Ameen Z; Collins A; Wojcik SE; Mair M; Young GS; Fuchs JR; Eubank TD; Frankel WL; Bekaii-Saab T; Bloomston M; Lesinski GB

INSTITUCIÓN / INSTITUTION:  - Internal Medicine, The Ohio State University.

RESUMEN / SUMMARY:  - Pancreatic stellate cells (PSC) are a subset of pancreatic cancer-associated fibroblasts. These cells provide pro-survival signals to tumors, however little is known regarding their interactions with immune cells within the tumor microenvironment. We hypothesized that factors produced by human PSC could enhance myeloid-derived suppressor cell (MDSC) differentiation and function, which promotes an immunosuppressive microenvironment. Primary PSC cell lines (n=7) were generated from human specimens and phenotypically confirmed via expression of vimentin, alpha-smooth muscle actin (alpha-SMA), and glial fibrillary acidic protein (GFAP). Luminex analysis indicated that PSC but not human fetal primary pancreatic fibroblast cells (HPF; negative controls) produced MDSC-promoting cytokines (IL-6, VEGF, M-CSF) and chemokines (SDF-1, MCP-1). Culture of peripheral blood mononuclear cells (PBMC, n=3 donors) with PSC supernatants or IL-6/GM-CSF (positive control) for 7 days promoted PBMC differentiation into an MDSC (CD11b+CD33+) phenotype and a sub-population of polymorphonuclear CD11b+CD33+CD15+ cells. The resulting CD11b+CD33+ cells functionally suppressed autologous T lymphocyte proliferation. In contrast, supernatants from HPF did not induce an MDSC phenotype in PBMCs. Culture of normal PBMCs with PSC supernatants led to STAT3 but not STAT1 or STAT5 phosphorylation. IL-6 was an important mediator as its neutralization inhibited PSC supernatant-mediated STAT3 phosphorylation and MDSC differentiation. Finally, the FLLL32 STAT3 inhibitor abrogated PSC supernatant-mediated MDSC differentiation, PSC viability, and reduced autocrine IL-6 production indicating  these processes are STAT3 dependent. These results identify a novel role for PSC  in driving immune escape in pancreatic cancer and extend the evidence that STAT3  acts as a driver of stromal immunosuppression to enhance its interest as a therapeutic target.

 

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[10]

TÍTULO / TITLE:  - Borderline Resectable Pancreatic Cancer: Need for Standardization and Methods for Optimal Clinical Trial Design.

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

REVISTA / JOURNAL:  - Ann Surg Oncol. 2013 Feb 23.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2886-9

AUTORES / AUTHORS:  - Katz MH; Marsh R; Herman JM; Shi Q; Collison E; Venook AP; Kindler HL; Alberts SR; Philip P; Lowy AM; Pisters PW; Posner MC; Berlin JD; Ahmad SA

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA, mhgkatz@mdanderson.org.

RESUMEN / SUMMARY:  - BACKGROUND: Methodological limitations of prior studies have prevented progress in the treatment of patients with borderline resectable pancreatic adenocarcinoma. Shortcomings have included an absence of staging and treatment standards and pre-existing biases with regard to the use of neoadjuvant therapy and the role of vascular resection at pancreatectomy. METHODS: In this manuscript, we review limitations of studies of borderline resectable PDAC reported to date, highlight important controversies related to this disease stage, emphasize the research infrastructure necessary for its future study, and  present a recently-approved Intergroup pilot study (Alliance A021101) that will provide a foundation upon which subsequent well-designed clinical trials can be performed. RESULTS: We identified twenty-three studies published since 2001 which report outcomes of patients with tumors labeled as borderline resectable and who  were treated with neoadjuvant therapy prior to planned pancreatectomy. These studies were heterogeneous in terms of the populations studied, the metrics used  to characterize therapeutic response, and the indications used to select patients for surgery. Mechanisms used to standardize these and other issues that are incorporated into Alliance A021101 are reviewed. CONCLUSIONS: Rigorous standards  of clinical trial design incorporated into trials of other disease stages must be adopted in all future studies of borderline resectable pancreatic cancer. The Intergroup trial should serve as a paradigm for such investigations.

 

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[11]

TÍTULO / TITLE:  - Phase II trial of erlotinib plus capecitabine as first-line treatment for metastatic pancreatic cancer (XELTA study).

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Feb;33(2):717-23.

AUTORES / AUTHORS:  - Lopez R; Mendez CM; Fernandez MJ; Reinoso CR; Aldana GQ; Fernandez MS; DE LA Camara Gomez J; Lopez MR; Vazquez MR; Folgar SC

INSTITUCIÓN / INSTITUTION:  - Servicio de Oncologia Medica, Complejo Hospitalario Universitario de Santiago de  Compostela, Travesia de Choupana s/n. 15706 Santiago de Compostela, España. Rafael.Lopez.Lopez@sergas.es

RESUMEN / SUMMARY:  - AIM: To evaluate the efficacy and safety of erlotinib plus capecitabine for metastatic pancreatic cancer. PATIENTS AND METHODS: This was a multicenter, uncontrolled, phase II trial. Patients with untreated metastatic pancreatic cancer received oral capecitabine at 1,000 mg/m(2) twice daily on days 1-14, of a 21-day treatment cycle; and oral erlotinib at 150 mg daily. RESULTS: Thirty-two patients were enrolled. The overall response rate (ORR) was 6%, with a median time to treatment failure of 2.1 months. The median follow-up was 7.6 months. The median progression-free survival was 2.1 months and median overall survival was 4.3 months. The one-year survival rate was 22%. Major grade 1 and 2 non-hematological toxicities were skin rash (34%), asthenia (31%) and diarrhea (31%). Grade 3 hematological toxicity was <13%. No grade 4 toxicities were detected. None of the patients died due to treatment toxicity. CONCLUSION: The combination of capecitabine with erlotinib is an active regimen with a favorable  safety profile for patients with metastatic pancreatic cancer.

 

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[12]

TÍTULO / TITLE:  - Disrupting Cytokine Signaling in Pancreatic Cancer: A Phase I/II Study of Etanercept in Combination With Gemcitabine in Patients With Advanced Disease.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279b87f

AUTORES / AUTHORS:  - Wu C; Fernandez SA; Criswell T; Chidiac TA; Guttridge D; Villalona-Calero M; Bekaii-Saab TS

INSTITUCIÓN / INSTITUTION:  - From the *Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research, Institute; daggerCenter for Biostatistics, The Ohio State University; and double daggerMark H Zangmeister Center, Columbus, OH.

RESUMEN / SUMMARY:  - OBJECTIVES: Etanercept blocks tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine that plays a role in cancer-related cachexia and tumor growth. A phase I/II study was conducted to assess the tolerability and efficacy  of gemcitabine and etanercept in advanced pancreatic cancer. METHODS: Twenty-five patients received etanercept 25 mg subcutaneously twice weekly with gemcitabine.  A control cohort of 8 patients received gemcitabine alone. The primary end point  was progression-free survival at 6 months. Blood specimens were analyzed for TNF-alpha, IL-1beta, IL-6, interferon-gamma, IL-10, and NF-kappabeta activation.  The trial is registered with ClinicalTrials.gov, number NCT00201838. RESULTS: Thirty-eight patients participated in this study. In the gemcitabine-etanercept cohort, grade ¾ drug-related toxicities included leucopenia (3) and neutropenia (6). There were 3 (12%) patients with partial response and 8 (32%) patients with  stable disease. The rate of progression-free survival at 6 months was 28% [n = 7; 95% confidence interval (CI), 20%-36%]. Median time to progression was 2.23 months (95% CI, 1.86-4.36 months) and median overall survival was 5.43 months (95% CI, 3.30-10.23 months). Clinical benefit rate was 33% of the evaluable patients. A correlation was seen between IL-10 levels and clinical benefit. CONCLUSIONS: Etanercept added to gemcitabine is safe but did not show significant enhancement of gemcitabine in patients with advanced pancreatic cancer.

 

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[13]

TÍTULO / TITLE:  - Enhancer of Zeste Homolog 2 Silences MicroRNA-218 in Human Pancreatic Ductal Adenocarcinoma Cells by Inducing Formation of Heterochromatin.

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

REVISTA / JOURNAL:  - Gastroenterology. 2013 Feb 7. pii: S0016-5085(13)00154-6. doi: 10.1053/j.gastro.2013.01.058.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.gastro.2013.01.058

AUTORES / AUTHORS:  - Li CH; To KF; Tong JH; Xiao Z; Xia T; Lai PA; Chow SC; Zhu YX; Chan SL; Marquez VE; Chen Y

INSTITUCIÓN / INSTITUTION:  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

RESUMEN / SUMMARY:  - BACKGROUND & AIMS: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is overexpressed by pancreatic ductal adenocarcinoma (PDAC) cells and increases their aggressiveness. We identified microRNAs (miRs) that are regulated by EZH2 and studied their functions in PDAC cells. METHODS: We performed miR profile analysis of PDAC cells incubated with EZH2 inhibitor 3-deazaneplanocin A, and pancreatic ductal epithelial cells that overexpressed EZH2. Expression levels of miRs and the targets of miRs were analyzed by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. We expressed different forms of EZH2 to analyze functional  domains and used small interfering RNAs to reduce its level in PDAC cells. RESULTS: Expression of miR-218 was repressed by EZH2 in PDAC cells. Levels of miR-218 were significantly reduced in primary PDAC tumor samples compared with paired, adjacent nontumor tissue. Overexpression of miR-218 in SW1990 cells reduced their proliferation and tumor formation and metastasis in nude mice. Loss of miR-218 from SW1990 cells increased levels of UDP-glycosyltransferase 8 and miR-218 was found to bind to its 3’ -UTR. Levels of UDP-glycosyltransferase protein and messenger RNA were associated with the metastatic potential of PDAC cell lines and progression of tumors in patients. EZH2 was found to silence miR-218 by binding to its promoter, promoting heterochromatin formation, and recruiting the DNAs methyltransferase 1, 3A, and 3B. CONCLUSIONS: EZH2 is up-regulated in PDAC samples from patients and silences miR-218. MicroRNA-218 prevents proliferation of PDAC cells in culture, and tumor growth and metastasis  in nude mice. MicroRNA-218 reduces levels of UDP-glycosyltransferase, which is associated with the metastatic potential of PDAC tumors in mice and progression of human PDAC.

 

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[14]

TÍTULO / TITLE:  - Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial.

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

REVISTA / JOURNAL:  - Lancet Oncol. 2013 Mar 5. pii: S1470-2045(13)70021-4. doi: 10.1016/S1470-2045(13)70021-4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/S1470-2045(13)70021-4

AUTORES / AUTHORS:  - Mukherjee S; Hurt CN; Bridgewater J; Falk S; Cummins S; Wasan H; Crosby T; Jephcott C; Roy R; Radhakrishna G; McDonald A; Ray R; Joseph G; Staffurth J; Abrams RA; Griffiths G; Maughan T

INSTITUCIÓN / INSTITUTION:  - Gray Institute for Radiation Oncology and Biology, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: somnath.mukherjee@oncology.ox.ac.uk.

RESUMEN / SUMMARY:  - BACKGROUND: In the UK, chemotherapy is the standard treatment for inoperable, locally advanced, non-metastatic pancreatic cancer. Chemoradiotherapy is also an  acceptable treatment option, for which gemcitabine, fluorouracil, or capecitabine can be used as concurrent chemotherapy agents. We aimed to assess the activity, safety, and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer. METHODS: In this open-label, randomised, two-arm, phase 2 trial, patients aged 18 years or older with histologically proven, locally advanced pancreatic cancer (with a tumour diameter of 7 cm or less) were recruited from 28 UK centres between Dec 24, 2009 and Oct 25, 2011. After 12 weeks of induction gemcitabine and capecitabine chemotherapy (three cycles of gemcitabine [1000 mg/m2 on days 1, 8, 15 of a 28-day cycle] and capecitabine [830 mg/m2 twice daily on days 1-21 of a 28-day cycle]), patients with stable or responding disease, tumour diameter of 6 cm or less, and WHO performance status 0-1 were randomly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine (300 mg/m2 once per week) or capecitabine (830 mg/m2 twice daily, Monday to Friday only), both in combination with radiation (50.4 Gy in 28 fractions). Randomisation (1:1) was done via a central computerised system and used stratified minimisation. The primary endpoint was 9-month progression-free survival, analysed by intention to  treat including only those patients with valid CT assessments. This trial is registered with ISRCTN, number 96169987. FINDINGS: 114 patients were registered and 74 were randomly allocated (38 to the gemcitabine group and 36 to the capecitabine group). After 9 months, 22 of 35 assessable patients (62.9%, 80% CI  50.6-73.9) in the capecitabine group and 18 of 35 assessable patients (51.4%, 39.4-63.4) in the gemcitabine group had not progressed. Median overall survival was 15.2 months (95% CI 13.9-19.2) in the capecitabine group and 13.4 months (95% CI 11.0-15.7) in the gemcitabine group (adjusted hazard ratio [HR] 0.39, 95% CI 0.18-0.81; p=0.012). 12-month overall survival was 79.2% (95% CI 61.1-89.5) in the capecitabine group and 64.2 (95% CI 46.4-77.5) in the gemcitabine group. Median progression-free survival was 12.0 months (95% CI 10.2-14.6) in the capecitabine group and 10.4 months (95% CI 8.9-12.5) in the gemcitabine group (adjusted HR 0.60, 95% CI 0.32-1.12; p=0.11). Eight patients in the capecitabine  group had an objective response at 26 weeks, as did seven in the gemcitabine group. More patients in the gemcitabine group than in the capecitabine group had  grade 3-4 haematological toxic effects (seven [18%] vs none, p=0.008) and non-haematological toxic effects (ten [26%] vs four [12%], p=0.12) during chemoradiation treatment; the most frequent events were leucopenia, neutropenia,  and fatigue. Two patients in the capecitabine group progressed during the fourth  cycle of induction chemotherapy. Of the 34 patients in the capecitabine group who received chemoradiotherapy, 25 (74%) received the full protocol dose of radiotherapy, compared with 26 (68%) of 38 patients in the gemcitabine group. Quality-of-life scores were not significantly different between the treatment groups. INTERPRETATION: Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer. However, these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small. FUNDING: Cancer Research UK.

 

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[15]

TÍTULO / TITLE:  - Pathohistological Subtype Predicts Survival in Patients With Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas.

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

REVISTA / JOURNAL:  - Ann Surg. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e318287ab73

AUTORES / AUTHORS:  - Distler M; Kersting S; Niedergethmann M; Aust DE; Franz M; Ruckert F; Ehehalt F; Pilarsky C; Post S; Saeger HD; Grutzmann R

INSTITUCIÓN / INSTITUTION:  - *Department of General, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany daggerDepartment of  General Surgery, Alfred Krupp Hospital, Essen, Germany double daggerInstitute for Pathology, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany section signDepartment of Surgery, University Hospital Mannheim, Mannheim, Germany.

RESUMEN / SUMMARY:  - OBJECTIVE:: To investigate different subtypes of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and their prognostic value. BACKGROUND:: IPMNs  of the pancreas are estimated to have a better prognosis than pancreatic ductal adenocarcinomas (PDACs). In addition to the different growth types (ie, main duct vs. branch duct types), the histological subtypes of IPMNs (ie, intestinal, pancreatobiliary, gastric, and oncocytic type) are prognostically relevant. These subtypes can be characterized by different mucin (MUC) expression patterns. In this study, we analyzed the IPMNs from 2 pancreatic cancer referral centers by correlating the MUC expression, histological subtype, and clinical outcome. METHODS:: We re-evaluated all resections due to a pancreatic tumor over a period  of 15 years. Cases with IPMNs were identified, and the subtypes were distinguished using histopathological analysis, including the immunohistochemical analysis of MUC (ie, MUC1, MUC2, and MUC5AC) expression. Furthermore, we determined clinical characteristics and patient outcome. RESULTS:: A total of 103 IPMNs were identified. On the basis of the MUC profile, histopathological subtypes were classified into the following categories: intestinal type [n = 45 (44%)], pancreatobiliary type [n = 41 (40%)], gastric type [n = 13 (12%)], and oncocytic type [n = 4 (4%)]. The following types of resections were performed: pancreatic head resections [n = 77 (75%)], tail resections [n = 16 (15%)], total  pancreatectomies [n = 5 (5%)], and segment resections [n = 5 (5%)]. The 5-year survival of patients with intestinal IPMNs was significantly better than pancreatobiliary IPMNs (86.6% vs. 35.6%; P < 0.001). The pancreatobiliary subtype was strongly associated with malignancy [odds ratio (OR): 6.76], recurrence (P <  0.001), and long-term survival comparable with that of PDAC patients. CONCLUSIONS:: Evaluation of IPMN subtypes supports postoperative patient prognosis prediction. Therefore, subtype differentiation could lead to improvements in clinical management. Potentially identifying subgroups with the need for adjuvant therapy may be possible.

 

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[16]

TÍTULO / TITLE:  - A prospective, comparative trial to optimize sampling techniques in EUS-guided FNA of solid pancreatic masses.

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

REVISTA / JOURNAL:  - Gastrointest Endosc. 2013 Feb 21. pii: S0016-5107(12)03062-3. doi: 10.1016/j.gie.2012.12.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gie.2012.12.009

AUTORES / AUTHORS:  - Lee JK; Choi JH; Lee KH; Kim KM; Shin JU; Lee JK; Lee KT; Jang KT

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Dongguk University, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - BACKGROUND: There is no standardization of the use of suction during puncturing of a target in pancreatic EUS-guided FNA (EUS-FNA). It is also debatable whether  expressing aspirates from the needle by the traditional method of reinserting the stylet is more effective than by air flushing, which is easier and safer. OBJECTIVE: To optimize sampling techniques in pancreatic EUS-FNA. DESIGN: Prospective, comparative trial. SETTING: Tertiary-care referral center. PATIENTS: Eighty-one consecutive patients with solid pancreatic masses. INTERVENTION: Four  punctures were performed for each mass in random order by a 2 x 2 factorial design. Sample quality and diagnostic yield were compared between samples with suction (S+) versus no suction (S-) and expressed by reinserting the stylet (RS)  versus air flushing (AF). MAIN OUTCOME MEASUREMENTS: Sample quality by the number of diagnostic samples, cellularity, bloodiness, and air-drying artifact; diagnostic yield by accuracy, sensitivity, and specificity. RESULTS: The number of diagnostic samples (72.8% vs 58.6%; P = .001), cellularity (odds ratio [OR] 2.12; 95% confidence interval [CI], 1.37-3.30; P < .001), bloodiness (OR 1.46; CI, 1.28-1.68; P < .001), accuracy (85.2% vs 75.9%; P = .004), and sensitivity (82.4% vs 72.1%; P = .005) were higher in S+ than in S-. Bloodiness was lower in  AF than in RS (OR 1.16; CI, 1.03-1.30; P = .017). LIMITATIONS: Single-center trial, 2 kinds of needle gauges, and no immediate cytopathology evaluation. CONCLUSION: Puncturing with suction and expressing by air flushing may be used preferentially in pancreatic EUS-FNA because they were more effective and convenient techniques. (Clinical trial registration number: NCT01354795.).

 

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[17]

TÍTULO / TITLE:  - Phase II randomised proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Mar 5;108(4):766-70. doi: 10.1038/bjc.2013.62. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.62

AUTORES / AUTHORS:  - Heinemann V; Ebert MP; Laubender RP; Bevan P; Mala 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.

RESUMEN / SUMMARY:  - Background:To evaluate the efficacy and tolerability of the urokinase plasminogen activator (uPA) inhibitor upamostat in combination with gemcitabine in locally advanced pancreatic adenocarcinoma (LAPC).Methods:Within a prospective multicenter study, LAPC patients were randomly assigned to receive 1000 mg m of gemcitabine IV weekly either alone (arm A) or in combination with 200 mg (arm B)  or 400 mg (arm C) oral upamostat daily. Efficacy endpoints of this proof-of-concept study included response rate, time to first metastasis, progression-free and overall survival (OS).Results:Of the 95 enroled patients, 85 were evaluable for response and 93 for safety. Median OS was 12.5 months (95% CI  8.2-18.2) in arm C, 9.7 months (95% CI 8.4-17.1) in arm B and 9.9 months (95% CI  7.4-12.1) in arm A; corresponding 1-year survival rates were 50.6%, 40.7% and 33.9%, respectively. More patients achieved a partial remission (confirmed responses by RECIST) with upamostat combination therapy (arm C: 12.9%; arm B: 7.1%; arm A: 3.8%). Overall, only 12 patients progressed by developing detectable distant metastasis (arm A: 4, arm B: 6, arm C: 2). The most common adverse events considered to be related to upamostat were asthenia, fever and nausea.Conclusion:In this proof-of-concept study targeting the uPA system in LAPC, the addition of upamostat to gemcitabine was tolerated well; similar survival results were observed for the three treatment arms.

 

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[18]

TÍTULO / TITLE:  - Up-regulation of p21WAF1/CIP1 by small activating RNA inhibits the in vitro and in vivo growth of pancreatic cancer cells.

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

REVISTA / JOURNAL:  - Tumori. 2012 Nov;98(6):804-11. doi: 10.1700/1217.13507.

            ●● Enlace al texto completo (gratuito o de pago) 1700/1217.13507

AUTORES / AUTHORS:  - Zhang Z; Wang Z; Liu X; Wang J; Li F; Li C; Shan B

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Road, Jinan, China.

RESUMEN / SUMMARY:  - AIMS AND BACKGROUND: To study the inhibitory effect of p21WAF1/CIP1 activation by saRNA on the growth of human pancreatic cancer cells PANC-1 in vitro and in vivo. METHODS AND STUDY DESIGN: A dsRNA (dsP21) targeting the p21WAF1/CIP1 gene promoter at position-322 relative to the transcription start site was transfected into PANC-1 cells. Expression of mRNA and protein was evaluated by semiquantitative RT-PCR and Western blotting. Proliferation of PANC-1 cells was measured by the MTT method, and the apoptosis rate was detected by flow cytometry. PANC-1 cells were transplanted subcutaneously in nude mice, and the inhibitory effect of dsP21 on tumor growth was observed. RESULTS: The introduction of dsP21 was shown to efficiently up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells according to the results of RT-PCR and Western  blotting (P <0.01, compared with controls). The inhibitory effect on cell proliferation was confirmed by the MTT test (P <0.05, compared with controls). The apoptosis rate of PANC-1 cells treated with dsP21 was significantly higher than that of the control cells (P <0.01). Our experimental data showed that dsP21-mediated up-regulation of p21 expression exerted an apparent growth inhibitory effect on PANC-1 cells in vivo. CONCLUSIONS: dsP21 targeting the p21WAF1/CIP1 gene promoter can specifically up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells. It therefore has a substantially inhibitory effect on cell proliferation in vitro and in vivo and can be used as a new method and material for the gene therapy of pancreatic cancer.

 

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[19]

TÍTULO / TITLE:  - Randomized trial comparing fanning with standard technique for endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic mass lesions.

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

REVISTA / JOURNAL:  - Endoscopy. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1326268

AUTORES / AUTHORS:  - Bang JY; Magee SH; Ramesh J; Trevino JM; Varadarajulu S

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

RESUMEN / SUMMARY:  - Background and study aims: The fanning technique for endoscopic ultrasound-guided fine-needle aspiration (EUS - FNA) involves sampling multiple areas within a lesion with each pass. The aim of this study was to compare the fanning and standard techniques for EUS - FNA of solid pancreatic masses.Patients and methods: Consecutive patients with solid pancreatic mass lesions were randomized  to undergo EUS - FNA using either the standard or the fanning technique. The main outcome measure was the median number of passes required to establish diagnosis.  The secondary outcome measures were the diagnostic accuracy, technical failure, and complication rate of the two techniques.Results: Of 54 patients, 26 were randomized to the standard technique and 28 to the fanning technique. There was no difference in diagnostic accuracy (76.9 % vs. 96.4 %; P = 0.05), technical failure or complication rates (none in either cohort). There was a significant difference in both the number of passes required to establish diagnosis (median 1 [interquartile range 1 - 3] vs. 1 [1 - 1]; P = 0.02) and the percentage of patients in whom a diagnosis was achieved on pass one (57.7 % vs. 85.7 %; P = 0.02) between the standard and fanning groups, respectively.Conclusions: The fanning technique of FNA was superior to the standard approach because fewer passes were required to establish the diagnosis. If these promising data are confirmed by other investigators, consideration should be given to incorporating  the fanning technique into routine practice of EUS - FNA. Registered at Clinical  Trials.gov (NCT 01501903).

 

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[20]

TÍTULO / TITLE:  - Histone deacetylase inhibitors and pancreatic cancer: Are there any promising clinical trials?

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

REVISTA / JOURNAL:  - World J Gastroenterol. 2013 Feb 28;19(8):1173-81. doi: 10.3748/wjg.v19.i8.1173.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i8.1173

AUTORES / AUTHORS:  - Koutsounas I; Giaginis C; Theocharis S

INSTITUCIÓN / INSTITUTION:  - Ioannis Koutsounas, Constantinos Giaginis, Stamatios Theocharis, Department of Forensic Medicine and Toxicology, Medical School, University of Athens, GR-11527  Athens, Greece.

RESUMEN / SUMMARY:  - Pancreatic cancer, although not very frequent, has an exceptionally high mortality rate, making it one of the most common causes of cancer mortality in developed countries. Pancreatic cancer is difficult to diagnose, allowing few patients to have the necessary treatment at a relatively early stage. Despite a marginal benefit in survival, the overall response of pancreatic cancer to current systemic therapy continues to be poor, and new therapies are desperately  needed. Histone deacetylase (HDAC) enzymes play an important role in the development and progression of cancer and HDAC inhibitors (HDACIs) have been shown to induce differentiation and cell cycle arrest, activate the extrinsic or  intrinsic pathways of apoptosis, and inhibit invasion, migration and angiogenesis in different cancer cell lines. As a result of promising preclinical data, various HDACIs are being tested as either monotherapeutic agents or in combination regimens for both solid and hematological malignancies. Vorinostat was the first HDACI approved by the Food and Drug Administration for patients with cutaneous T-cell lymphoma. The use of HDACIs in clinical trials, in pretreated and relapsed patients suffering from advanced pancreatic cancer is discussed. Unfortunately, clinical data for HDACIs in patients with pancreatic cancer are inadequate, because only a few studies have included patients suffering from this type of neoplasm and the number of pancreatic cancer patients that entered HDACIs phase II/III trials, among others with advanced solid tumors, is very limited. More studies recruiting patients with pancreatic cancer remain to determine the efficiency of these therapies.

 

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[21]

TÍTULO / TITLE:  - Restoration of Mannose-Binding Lectin Complement Activity Is Associated With Improved Outcome in Patients With Advanced Pancreatic Cancer Treated With Gemcitabine and Intravenous omega-3 Fish Oil.

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

REVISTA / JOURNAL:  - JPEN J Parenter Enteral Nutr. 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0148607113476304

AUTORES / AUTHORS:  - Arshad A; Chung W; Isherwood J; Steward W; Metcalfe M; Dennison A

INSTITUCIÓN / INSTITUTION:  - Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Leicester, UK.

RESUMEN / SUMMARY:  - Background: Pancreatic cancer has an extremely poor clinical outcome. Surrogate biomarkers for outcome are scarce. There is mixed evidence for the association of high mannose-binding lectin (MBL) complement activity with cancer outcomes, including reduced survival and increased infectious complications. omega-3-rich fatty acids (omega-3FA) attenuate production of proinflammatory cytokines and potentially manipulate complement activity. Materials and Methods: As part of a single-arm phase II trial in a university hospital, patients with advanced pancreatic adenocarcinoma were treated with weekly omega-3FA-rich intravenous infusion (Lipidem [B. Braun Melsungen AG, Melsungen, Germany]: up to 100 g/wk) plus gemcitabine chemotherapy until withdrawal or tumor progression. Primary outcome measure was objective response rate. Changes in complement activity, which were a secondary outcome measure, were analyzed and relation to clinical outcome determined. Results: Twenty-three patients were assessable for time to progression (TTP), overall survival (OS), and complement activity. No hypoactivity in alternative and classical pathways was demonstrated. Baseline MBL was low in 10 of 23 patients (43.5%). There was no difference in OS or TTP between low- and high-baseline MBL patients. Of these 10 patients, 5 were classified as MBL responders. MBL responders had a tendency toward improved OS over nonresponders (8.9 vs 4.4 months, P = .07). MBL responders had significantly improved TTP over nonresponders (10.6 vs 5.3 months, P = .03). Conclusion: MBL restoration had an association with improved outcome in the cohort of patients with low MBL activity at baseline. The independent contribution of omega-3FA to this effect warrants further investigation in the form of randomized clinical trials.

 

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[22]

TÍTULO / TITLE:  - Phosphorylation on Ser-279 and Ser-282 of connexin43 regulates endocytosis and gap junction assembly in pancreatic cancer cells.

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

REVISTA / JOURNAL:  - Mol Biol Cell. 2013 Mar;24(6):715-33. doi: 10.1091/mbc.E12-07-0537. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1091/mbc.E12-07-0537

AUTORES / AUTHORS:  - Johnson KE; Mitra S; Katoch P; Kelsey LS; Johnson KR; Mehta PP

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry and Molecular Biology and Department of Oral Biology,  Eppley Institute for Research in Cancer and Allied Diseases, Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198.

RESUMEN / SUMMARY:  - The molecular mechanisms regulating the assembly of connexins (Cxs) into gap junctions are poorly understood. Using human pancreatic tumor cell lines BxPC3 and Capan-1, which express Cx26 and Cx43, we show that, upon arrival at the cell  surface, the assembly of Cx43 is impaired. Connexin43 fails to assemble, because  it is internalized by clathrin-mediated endocytosis. Assembly is restored upon expressing a sorting-motif mutant of Cx43, which does not interact with the AP2 complex, and by expressing mutants that cannot be phosphorylated on Ser-279 and Ser-282. The mutants restore assembly by preventing clathrin-mediated endocytosis of Cx43. Our results also document that the sorting-motif mutant is assembled into gap junctions in cells in which the expression of endogenous Cx43 has been knocked down. Remarkably, Cx43 mutants that cannot be phosphorylated on Ser-279 or Ser-282 are assembled into gap junctions only when connexons are composed of Cx43 forms that can be phosphorylated on these serines and forms in which phosphorylation on these serines is abolished. Based on the subcellular fate of Cx43 in single and contacting cells, our results document that the endocytic itinerary of Cx43 is altered upon cell-cell contact, which causes Cx43 to traffic by EEA1-negative endosomes en route to lysosomes. Our results further show that gap-junctional plaques formed of a sorting motif-deficient mutant of Cx43, which  is unable to be internalized by the clathrin-mediated pathway, are predominantly  endocytosed in the form of annular junctions. Thus the differential phosphorylation of Cx43 on Ser-279 and Ser-282 is fine-tuned to control Cx43’s endocytosis and assembly into gap junctions.

 

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[23]

TÍTULO / TITLE:  - Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma.

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

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3919-24. doi: 10.1073/pnas.1219555110. Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1219555110

AUTORES / AUTHORS:  - Guillaumond F; Leca J; Olivares O; Lavaut MN; Vidal N; Berthezene P; Dusetti NJ; Loncle C; Calvo E; Turrini O; Iovanna JL; Tomasini R; Vasseur S

INSTITUCIÓN / INSTITUTION:  - Centre de Recherche en Cancerologie de Marseille (CRCM), Unite 1068, Institut National de la Sante et de la Recherche Medicale, F-13009 Marseille, France.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma is one of the most intractable and fatal cancer. The decreased blood vessel density displayed by this tumor not only favors its resistance to chemotherapy but also participates in its aggressiveness due to the consequent high degree of hypoxia. It is indeed clear that hypoxia promotes selective pressure on malignant cells that must develop adaptive metabolic responses to reach their energetic and biosynthetic demands. Here, using a well-defined mouse model of pancreatic cancer, we report that hypoxic areas from  pancreatic ductal adenocarcinoma are mainly composed of epithelial cells harboring epithelial-mesenchymal transition features and expressing glycolytic markers, two characteristics associated with tumor aggressiveness. We also show that hypoxia increases the “glycolytic” switch of pancreatic cancer cells from oxydative phosphorylation to lactate production and we demonstrate that increased lactate efflux from hypoxic cancer cells favors the growth of normoxic cancer cells. In addition, we show that glutamine metabolization by hypoxic pancreatic tumor cells is necessary for their survival. Metabolized glucose and glutamine converge toward a common pathway, termed hexosamine biosynthetic pathway, which allows O-linked N-acetylglucosamine modifications of proteins. Here, we report that hypoxia increases transcription of hexosamine biosynthetic pathway genes as  well as levels of O-glycosylated proteins and that O-linked N-acetylglucosaminylation of proteins is a process required for hypoxic pancreatic cancer cell survival. Our results demonstrate that hypoxia-driven metabolic adaptive processes, such as high glycolytic rate and hexosamine biosynthetic pathway activation, favor hypoxic and normoxic cancer cell survival  and correlate with pancreatic ductal adenocarcinoma aggressiveness.

 

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[24]

TÍTULO / TITLE:  - ABO blood groups and pancreatic cancer risk and survival: results from the PANcreatic Disease ReseArch (PANDoRA) consortium.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Apr;29(4):1637-44. doi: 10.3892/or.2013.2285. Epub 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2285

AUTORES / AUTHORS:  - Rizzato C; Campa D; Pezzilli R; Soucek P; Greenhalf W; Capurso G; Talar-Wojnarowska R; Heller A; Jamroziak K; Khaw KT; Key TJ; Bambi F; Landi S; Mohelnikova-Duchonova B; Vodickova L; Buchler MW; Bugert P; Vodicka P; Neoptolemos JP; Werner J; Hoheisel JD; Bauer AS; Giese N; Canzian F

INSTITUCIÓN / INSTITUTION:  - Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

RESUMEN / SUMMARY:  - There is strong epidemiologic evidence indicating that common genetic variability could be implicated in pancreatic cancer risk and, to date, various loci have been proposed. In particular, there is increasing evidence of the involvement of  ABO gene variability and pancreatic cancer risk. In a large multicentric study of 1,028 pancreatic ductal adenocarcinoma cases and 2,257 controls in the context of the PANcreatic Disease ReseArch (PANDoRA) consortium, we investigated the suggested association with increased risk for carriers of single nucleotide polymorphisms (SNPs) determining the A or B allele in comparison with the O allele, which encodes for a non-functional enzyme. Since glycosyltransferase activity, encoded by ABO, is higher for the A1 variant compared with the A2 variant, we investigated the hypothesis that A1 carriers were at an increased risk of pancreatic cancer. In our analysis, carriers of the A1 were indeed at greater risk of developing the disease. In addition, we investigated the possible influence that genetic variability at the ABO locus may have in pancreatic cancer survival, but we observed no effect in our population.

 

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[25]

TÍTULO / TITLE:  - Hypoglycemia reduces vascular endothelial growth factor a production by pancreatic Beta cells as a regulator of Beta cell mass.

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

REVISTA / JOURNAL:  - J Biol Chem. 2013 Mar 22;288(12):8636-46. doi: 10.1074/jbc.M112.422949. Epub 2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.422949

AUTORES / AUTHORS:  - Xiao X; Guo P; Chen Z; El-Gohary Y; Wiersch J; Gaffar I; Prasadan K; Shiota C; Gittes GK

INSTITUCIÓN / INSTITUTION:  - From the Division of Pediatric Surgery, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.

RESUMEN / SUMMARY:  - VEGF-A expression in beta cells is critical for pancreatic development, formation of islet-specific vasculature, and Insulin secretion. However, two key questions  remain. First, is VEGF-A release from beta cells coupled to VEGF-A production in  beta cells? Second, how is the VEGF-A response by beta cells affected by metabolic signals? Here, we show that VEGF-A secretion, but not gene transcription, in either cultured islets or purified pancreatic beta cells, was significantly reduced early on during low glucose conditions. In vivo, a sustained hypoglycemia in mice was induced with Insulin pellets, resulting in a significant reduction in beta cell mass. This loss of beta cell mass could be significantly rescued with continuous delivery of exogenous VEGF-A, which had no  effect on beta cell mass in normoglycemic mice. In addition, an increase in apoptotic endothelial cells during hypoglycemia preceded an increase in apoptotic beta cells. Both endothelial and beta cell apoptosis were prevented by exogenous  VEGF-A, suggesting a possible causative relationship between reduced VEGF-A and the loss of islet vasculature and beta cells. Furthermore, in none of these experimental groups did beta cell proliferation and islet vessel density change,  suggesting a tightly regulated balance between these two cellular compartments. The average islet size decreased in hypoglycemia, which was also prevented by exogenous VEGF-A. Taken together, our data suggest that VEGF-A release in beta cells is independent of VEGF-A synthesis. Beta cell mass can be regulated through modulated release of VEGF-A from beta cells based on physiological need.

 

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[26]

TÍTULO / TITLE:  - An unusual cause of pancreatic mass lesion.

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

REVISTA / JOURNAL:  - Gastroenterology. 2013 Apr;144(4):e3-4. doi: 10.1053/j.gastro.2012.11.029. Epub 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.gastro.2012.11.029

AUTORES / AUTHORS:  - Panic N; Inzani F; Larghi A

INSTITUCIÓN / INSTITUTION:  - Digestive Endoscopy Unit, Catholic University, Rome, Italy; Department of Public  Health, Catholic University, Rome, Italy; University of Belgrade, Belgrade, Serbia.

 

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[27]

TÍTULO / TITLE:  - Microparticle-associated tissue factor activity in patients with pancreatic cancer: correlation with clinicopathological features.

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

REVISTA / JOURNAL:  - Eur J Clin Invest. 2013 Mar;43(3):277-85. doi: 10.1111/eci.12042. Epub 2013 Feb 9.

            ●● Enlace al texto completo (gratuito o de pago) 1111/eci.12042

AUTORES / AUTHORS:  - Thaler J; Ay C; Mackman N; Metz-Schimmerl S; Stift J; Kaider A; Mullauer L; Gnant M; Scheithauer W; Pabinger I

INSTITUCIÓN / INSTITUTION:  - Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

RESUMEN / SUMMARY:  - BACKGROUND: Patients with pancreatic cancer have an unfavourable prognosis. A central role in pancreatic cancer progression has been suggested for tissue factor (TF), the main initiator of the blood coagulation cascade. We hypothesized that elevated levels of plasma microparticle (MP)-associated TF activity might indicate the presence of poorly differentiated pancreatic cancer, disease dissemination and infiltration of peripancreatic vessels. METHODS: MP-TF activity was measured in 73 pancreatic cancer patients and 22 healthy controls. Abdominal  computerized tomography (CT) scans performed at study inclusion were investigated for probability of tumoural vascular invasion. In addition, intratumoural TF expression, D-dimer and CA 19-9 levels were determined. RESULTS: MP-TF activity (pg/mL) was significantly higher in patients (median: 0.37 [range: 0.00-11.91]) than in controls (median: 0.05 [range: 0.00-0.76]; P < 0.001). When pancreatic cancer patients were compared with regard to stage and grade, significantly elevated levels of MP-TF activity were only present in those with poorly differentiated metastatic nonresectable tumours (n = 11, median: 2.95 [range: 0.25-11.91]). In three patients with poorly differentiated tumours, a high probability of vascular invasion was found (MP-TF activity in these cases: 2.95,  7.00 and 10.34). MP-TF activity correlated strongly with CA 19-9 (r = 0.60) and weakly with D-dimer (r = 0.33) levels. Immunohistochemical staining for TF was positive in 14 of 15 resected tumours. MP-TF activity was associated with an increased risk of mortality (HR: 1.8 per doubling in MP-TF activity, [95% CI: 1.4-2.4, P < 0.001]). CONCLUSION: MP-TF activity might represent a biomarker for  a poorly differentiated and invasive pancreatic cancer phenotype and poor survival.

 

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[28]

TÍTULO / TITLE:  - Everolimus in advanced pancreatic neuroendocrine tumors: the clinical experience.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Mar 1;73(5):1449-53. doi: 10.1158/0008-5472.CAN-12-3923. Epub 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3923

AUTORES / AUTHORS:  - Yao JC; Phan AT; Jehl V; Shah G; Meric-Bernstam F

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Gastrointestinal Medical Oncology and Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Novartis Pharmaceuticals Corporation, Basel, Switzerland; and Novartis Pharmaceuticals Corporation, Florham Park, New Jersey.

RESUMEN / SUMMARY:  - The incidence of neuroendocrine tumors (NET) has increased dramatically in the past 30 years. This information has revitalized basic and clinical research into  the molecular biology of NET and has resulted in the recent approval of new therapies for pancreatic NET (pNET), including the oral inhibitor of the mTOR everolimus. Everolimus significantly improved progression-free survival among patients with pNET in the phase III RADIANT-3 study. Here, we review the clinical studies showing the efficacy of everolimus in pNET and summarize the translational science from these studies. To understand the mechanisms of resistance and cause of treatment failure, we compared the type of progression events observed in the everolimus and placebo arms of the RADIANT-3 study. Comparison of the everolimus arm to the placebo arm indicated the fractions of progression events due to new metastasis only (21% vs. 22%), growth of preexisting lesions only (54% vs. 49%), and new metastasis along with growth of preexisting lesions (24% vs. 27%) were similar. These results suggest that although everolimus delays disease progression in patients with pNET, patients who experience disease progression while on everolimus do not appear to have a more aggressive metastatic phenotype than those whose disease progresses while on placebo. Cancer Res; 73(5); 1449-53. ©2013 AACR.

 

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[29]

TÍTULO / TITLE:  - KRAS mutation status is not predictive for objective response to anti-EGFR treatment with erlotinib in patients with advanced pancreatic cancer.

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

REVISTA / JOURNAL:  - J Gastroenterol. 2013 Feb 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00535-013-0767-4

AUTORES / AUTHORS:  - Boeck S; Jung A; Laubender RP; Neumann J; Egg R; Goritschan C; Ormanns S; Haas M; Modest DP; Kirchner T; Heinemann V

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

RESUMEN / SUMMARY:  - BACKGROUND: It has not yet been defined if KRAS has a prognostic value or is a predictive biomarker for the efficacy of erlotinib in advanced pancreatic cancer  (PC). METHODS: AIO-PK0104 was a phase III trial comparing gemcitabine/erlotinib followed by capecitabine with capecitabine/erlotinib followed by gemcitabine in advanced PC. For this post hoc subgroup analysis, biomarker data on the KRAS exon 2 mutation status were correlated with objective response to 1st-line therapy and with overall survival after start of 2nd-line chemotherapy (OSc). RESULTS: KRAS codon 12 was mutated in 121 of 173 (70 %) patients. The KRAS status showed no association with objective response (p = 0.40), but KRAS wildtype patients had an improved OS (HR 1.68, p = 0.005). A trend for a survival benefit was also observed during (non-erlotinib containing) 2nd-line chemotherapy, with a HR of 1.47 (p = 0.10) for the OSc. CONCLUSION: This post hoc analysis of AIO-PK0104 supports the assumption that KRAS is rather a prognostic than a predictive biomarker in PC.

 

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[30]

TÍTULO / TITLE:  - Bitter melon juice activates cellular energy sensor AMP-activated protein kinase  causing apoptotic death of human pancreatic carcinoma cells.

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

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt081

AUTORES / AUTHORS:  - Kaur M; Deep G; Jain AK; Raina K; Agarwal C; Wempe MF; Agarwal R

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences and.

RESUMEN / SUMMARY:  - Prognosis of pancreatic cancer is extremely poor, suggesting critical needs for additional drugs to improve disease outcome. In this study, we examined efficacy  and associated mechanism of a novel agent bitter melon juice (BMJ) against pancreatic carcinoma cells both in culture and nude mice. BMJ anticancer efficacy was analyzed in human pancreatic carcinoma BxPC-3, MiaPaCa-2, AsPC-1 and Capan-2  cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide, cell death enzyme-linked immunosorbent assay and annexin/propidium iodide assays. BMJ  effect on apoptosis regulators was assessed by immunoblotting. In vivo BMJ efficacy was evaluated against MiaPaCa-2 tumors in nude mice, and xenograft was analyzed for biomarkers by immunohistochemistry (IHC). Results showed that BMJ (2-5% v/v) decreases cell viability in all four pancreatic carcinoma cell lines by inducing strong apoptotic death. At molecular level, BMJ caused caspases activation, altered expression of Bcl-2 family members and cytochrome-c release into the cytosol. Additionally, BMJ decreased survivin and X-linked inhibitor of  apoptosis protein but increased p21, CHOP and phosphorylated mitogen-activated protein kinases (extracellular signal-regulated kinase ½ and p38) levels. Importantly, BMJ activated adenosine monophosphate-activated protein kinase (AMPK), a biomarker for cellular energy status, and an AMPK inhibitor (Compound C) reversed BMJ-induced caspase-3 activation suggesting activated AMPK involvement in BMJ-induced apoptosis. In vivo, oral administration of lyophilized BMJ (5mg in 100 microl water/day/mouse) for 6 weeks inhibited MiaPaCa-2 tumor xenograft growth by 60% (P < 0.01) without noticeable toxicity in nude mice. IHC  analyses of MiaPaCa-2 xenografts showed that BMJ also inhibits proliferation, induces apoptosis and activates AMPK in vivo. Overall, BMJ exerts strong anticancer efficacy against human pancreatic carcinoma cells, both in vitro and in vivo, suggesting its clinical usefulness.

 

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[31]

TÍTULO / TITLE:  - Marked Expansion of Exocrine and Endocrine Pancreas with Incretin Therapy in Humans with increased Exocrine Pancreas Dysplasia and the potential for Glucagon-producing Neuroendocrine Tumors.

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

REVISTA / JOURNAL:  - Diabetes. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 2337/db12-1686

AUTORES / AUTHORS:  - Butler AE; Campbell-Thompson M; Gurlo T; Dawson DW; Atkinson M; Butler PC

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California.

RESUMEN / SUMMARY:  - Controversy exists regarding the potential regenerative influences of incretin therapy on pancreatic beta cells versus possible adverse pancreatic proliferative effects. Examination of pancreata from age matched organ donors with type 2 diabetes (DM) treated by incretin therapy (n=8) or other therapy (n=12) and non diabetic controls (n=14) reveals a approximately 40% increased pancreatic mass in DM treated with incretin therapy with both increased exocrine cell proliferation  (p<0.0001) and dysplasia (increased pancreatic intraepithelia neoplasia, p<0.01). Pancreas in DM treated with incretin therapy was notable for alpha cell hyperplasia and glucagon expressing microadenomas (3/8) and a neuroendocrine tumor. beta cell mass was reduced by approximately 60% in those with DM, yet a 6  fold increase was observed in incretin treated subjects although diabetes persists. Endocrine cells co-staining for insulin and glucagon were increased in  DM compared to non diabetic controls (p<0.05) and markedly further increased by incretin therapy (p<0.05). In conclusion, in humans, incretin therapy resulted in a marked expansion of the exocrine and endocrine pancreatic compartments, the former being accompanied by increased proliferation and dysplasia, the latter by  alpha cell hyperplasia with the potential for evolution into neuroendocrine tumors.

 

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[32]

TÍTULO / TITLE:  - Holy Basil leaf extract decreases tumorigenicity and metastasis of aggressive human pancreatic cancer cells in vitro and in vivo: Potential role in therapy.

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

REVISTA / JOURNAL:  - Cancer Lett. 2013 Mar 21. pii: S0304-3835(13)00245-0. doi: 10.1016/j.canlet.2013.03.017.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.03.017

AUTORES / AUTHORS:  - Shimizu T; Torres MP; Chakraborty S; Souchek JJ; Rachagani S; Kaur S; Macha M; Ganti AK; Hauke RJ; Batra SK

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry and Molecular Biology, University of Nebraska Medical  Center, Omaha, NE, USA.

RESUMEN / SUMMARY:  - There is an urgent need to develop alternative therapies against lethal pancreatic cancer (PC). Ocimum sanctum (“Holy Basil”) has been used for thousands of years in traditional Indian medicine, but its anti-tumorigenic effect remains  largely unexplored. Here, we show that extracts of O. sanctum leaves inhibit the  proliferation, migration, invasion, and induce apoptosis of PC cells in vitro. The expression of genes that promote the proliferation, migration and invasion of PC cells including activated ERK-1/2, FAK, and p65 (subunit of NF-kappaB), was downregulated in PC cells after O. sanctum treatment. Intraperitoneal injections  of the aqueous extract significantly inhibited the growth of orthotopically transplanted PC cells in vivo (p<0.05). Genes that inhibit metastasis (E-cadherin) and induce apoptosis (BAD) were significantly upregulated in tumors  isolated from mice treated with O. sanctum extracts, while genes that promote survival (Bcl-2 and Bcl-xL) and chemo/radiation resistance (AURKA, Chk1 and Survivin) were downregulated. Overall, our study suggests that leaves of O. sanctum could be a potential source of novel anticancer compounds in the future.

 

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[33]

TÍTULO / TITLE:  - Safety and efficacy of neoadjuvant FOLFIRINOX treatment in a series of patients with borderline resectable pancreatic ductal adenocarcinoma.

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

REVISTA / JOURNAL:  - Acta Oncol. 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2013.771821

AUTORES / AUTHORS:  - Tinchon C; Hubmann E; Pichler A; Keil F; Pichler M; Rabl H; Uggowitzer M; Jilek K; Leitner G; Bauernhofer T

INSTITUCIÓN / INSTITUTION:  - Department of Hemato-Oncology , General Hospital Leoben , Austria.

 

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[34]

TÍTULO / TITLE:  - Targeting miR-21 for the Therapy of Pancreatic Cancer.

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

REVISTA / JOURNAL:  - Mol Ther. 2013 Mar 12. doi: 10.1038/mt.2013.35.

            ●● Enlace al texto completo (gratuito o de pago) 1038/mt.2013.35

AUTORES / AUTHORS:  - Sicard F; Gayral M; Lulka H; Buscail L; Cordelier P

INSTITUCIÓN / INSTITUTION:  - 1] INSERM U1037, Cancer Research Center of Toulouse, Toulouse, France [2] Universite Paul Sabatier Toulouse III, Toulouse, France.

RESUMEN / SUMMARY:  - Despite tremendous efforts worldwide from clinicians and cancer scientists, pancreatic ductal adenocarcinoma (PDA) remains a deadly disease for which no cure is available. Recently, microRNAs (miRNAs) have emerged as key actors in carcinogenesis and we demonstrated that microRNA-21 (miR-21), oncomiR is expressed early during PDA. In the present study, we asked whether targeting miR-21 in human PDA-derived cell lines using lentiviral vectors (LVs) may impede  tumor growth. We demonstrated that LVs-transduced human PDA efficiently downregulated miR-21 expression, both in vitro and in vivo. Consequently, cell proliferation was strongly inhibited and PDA-derived cell lines died by apoptosis through the mitochondrial pathway. In vivo, miR-21 depletion stopped the progression of a very aggressive model of PDA, to induce cell death by apoptosis; furthermore, combining miR-21 targeting and chemotherapeutic treatment provoked tumor regression. We demonstrate herein for the first time that targeting oncogenic miRNA strongly inhibit pancreatic cancer tumor growth both in vitro and in vivo. Because miR-21 is overexpressed in most human tumors; therapeutic delivery of miR-21 antagonists may still be beneficial for a large number of cancers for which no cure is available.Molecular Therapy (2013); doi:10.1038/mt.2013.35.

 

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[35]

TÍTULO / TITLE:  - KRAS Mutations and Their Correlation With Survival of Patients With Advanced Pancreatic Cancer.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Apr;42(3):543-544.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826b388b

AUTORES / AUTHORS:  - Bournet B; Muscari F; Guimbaud R; Cordelier P; Buscail L

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology and INSERM U1037 University Hospital Center Rangueil-Larrey CHU of Toulouse University Paul Sabatier Toulouse, France Department of Digestive Surgery University Hospital Center Rangueil-Larrey CHU of Toulouse University Paul Sabatier Toulouse, France Department of Oncology University Hospital Center Rangueil-Larrey CHU of Toulouse University Paul Sabatier Toulouse, France INSERM U1037 University Hospital Center Rangueil-Larrey University Paul Sabatier Toulouse, France Department of Gastroenterology and INSERM U1037 University Hospital Center Rangueil-Larrey CHU of Toulouse University Paul Sabatier Toulouse, France Buscail.L@chu-toulouse.fr.

 

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[36]

TÍTULO / TITLE:  - Alkaline Phosphatase ALPPL-2 Is a Novel Pancreatic Carcinoma-Associated Protein.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Mar 15;73(6):1934-45. doi: 10.1158/0008-5472.CAN-12-3682. Epub 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3682

AUTORES / AUTHORS:  - Dua P; Kang HS; Hong SM; Tsao MS; Kim S; Lee DK

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Department of Medical Biotechnology, Dongguk University; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul; Global Research Laboratory of RNAi Medicine, Department of Chemistry, Sungkyunkwan University, Suwon, Korea; and Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Canada.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a  very low median survival rate. The lack of early sensitive diagnostic markers is  one of the main causes of PDAC-associated lethality. Therefore, to identify novel pancreatic cancer biomarkers that can facilitate early diagnosis and also help in the development of effective therapeutics, we developed RNA aptamers targeting pancreatic cancer by Cell-systematic evolution of ligands by exponential enrichment (SELEX) approach. Using a selection strategy that could generate aptamers for 2 pancreatic cancer cell lines in one selection scheme, we identified an aptamer SQ-2 that could recognize pancreatic cancer cells with high specificity. Next, by applying 2 alternative approaches: (i) aptamer-based target pull-down and (ii) genome-wide microarray-based identification of differentially  expressed mRNAs in aptamer-positive and -negative cells, we identified alkaline phosphatase placental-like 2 (ALPPL-2), an oncofetal protein, as the target of SQ-2. ALPPL-2 was found to be ectopically expressed in many pancreatic cancer cell lines at both mRNA and protein levels. RNA interference-mediated ALPPL-2 knockdown identified novel tumor-associated functions of this protein in pancreatic cancer cell growth and invasion. In addition, the aptamer-mediated identification of ALPPL-2 on the cell surface and cell secretions of pancreatic cancer cells supports its potential use in the serum- and membrane-based diagnosis of PDAC. Cancer Res; 73(6); 1934-45. ©2012 AACR.

 

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[37]

TÍTULO / TITLE:  - Anxiety and perception of cancer risk in patients undergoing endoscopic ultrasonography for pancreas cystic lesions.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Apr;42(3):548-9. doi: 10.1097/MPA.0b013e31826b39bb.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826b39bb

AUTORES / AUTHORS:  - Shieh FK; Siddiqui UD; Padda M; Dharan M; Rossi F; Aslanian HR

INSTITUCIÓN / INSTITUTION:  - Section of Digestive DiseasesYale University New Haven, CT fshieh@gmail.com.

 

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[38]

TÍTULO / TITLE:  - Species-specific vesicular monoamine transporter 2 (VMAT2) expression in mammalian pancreatic beta cells: implications for optimising radioligand-based human beta cell mass (BCM) imaging in animal models.

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

REVISTA / JOURNAL:  - Diabetologia. 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00125-013-2847-7

AUTORES / AUTHORS:  - Schafer MK; Hartwig NR; Kalmbach N; Klietz M; Anlauf M; Eiden LE; Weihe E

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University Marburg, Robert-Koch-Strasse 8, 35037, Marburg, Germany, mkh.schafer@staff.uni-marburg.de.

RESUMEN / SUMMARY:  - AIMS/HYPOTHESIS: Imaging of beta cell mass (BCM) is a major challenge in diabetes research. The vesicular monoamine transporter 2 (VMAT2) is abundantly expressed in human beta cells. Radiolabelled analogues of tetrabenazine (TBZ; a low-molecular-weight, cell-permeant VMAT2-selective ligand) have been employed for pancreatic islet imaging in humans. Since reports on TBZ-based VMAT2 imaging  in rodent pancreas have been fraught with confusion, we compared VMAT2 gene expression patterns in the mouse, rat, pig and human pancreas, to identify appropriate animal models with which to further validate and optimise TBZ imaging in humans. METHODS: We used a panel of highly sensitive VMAT2 antibodies developed against equivalently antigenic regions of the transporter from each species in combination with immunostaining for insulin and species-specific in situ hybridisation probes. Individual pancreatic islets were obtained by laser-capture microdissection and subjected to analysis of mRNA expression of VMAT2. RESULTS: The VMAT2 protein was not expressed in beta cells in the adult pancreas of common mouse or rat laboratory strains, in contrast to its expression in beta cells (but not other pancreatic endocrine cell types) in the pancreas of  pigs and humans. VMAT2- and tyrosine hydroxylase co-positive (catecholaminergic)  innervation was less abundant in humans than in rodents. VMAT2-positive mast cells were identified in the pancreas of all species. CONCLUSIONS/INTERPRETATION: Primates and pigs are suitable models for TBZ imaging of beta cells. Rodents, because of a complete lack of VMAT2 expression in the endocrine pancreas, are a ‘null’ model for assessing interference with BCM measurements by VMAT2-positive mast cells and sympathetic innervation in the pancreas.

 

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[39]

TÍTULO / TITLE:  - Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy.

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

REVISTA / JOURNAL:  - Cancer Gene Ther. 2013 Mar 8. doi: 10.1038/cgt.2013.9.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2013.9

AUTORES / AUTHORS:  - Camp ER; Wang C; Little EC; Watson PM; Pirollo KF; Rait A; Cole DJ; Chang EH; Watson DK

INSTITUCIÓN / INSTITUTION:  - 1] Department of Surgery, Medical University of South Carolina, Charleston, SC, USA [2] Ralph H Johnson VA Medical Center, Charleston, SC, USA.

RESUMEN / SUMMARY:  - To overcome gene therapy barriers such as low transfection efficiency and nonspecific delivery, liposomal nanoparticles targeted by a single-chain antibody fragment to the transferrin receptor (TfRscFv) delivering wild-type (wt) human p53 (SGT-53) were developed for tumor-specific targeting. We hypothesize that SGT-53 in combination with gemcitabine will demonstrate enhanced therapeutic benefit in an in vivo metastatic pancreatic cancer model. Intrasplenic injection  of 1 x 106 Panc02 murine pancreatic cancer cells was used to generate in vivo hepatic metastatic tumors. Nanoparticle localization was assessed by tail vein injection of TfRscFv with fluorescently labeled oligonucleotides (6-carboxyfluorescein phosphoramidite (6FAM) ODN) imaged by Xenogen IVIS 200 scan. SGT-53 (equivalent to 30 mug of p53 intravenously) and gemcitabine (20 mg/kg intraperitoneally) alone and in combination were administered biweekly and  compared with untreated mice. Survival was determined by blinded daily assessment of morbidity. Human wtp53 expression and transferrin levels in the tumors were assessed by western blot analysis. Tumor burden was quantified by liver weight. Xenogen imaging demonstrated tumor-specific uptake of TfRscFv-6FAM ODN. Exogenous human wtp53 protein was detected in the SGT-53-treated tumors compared with control. Compared with untreated mice with metastatic tumors demonstrating median survival of 20 days, SGT-53, gemcitabine and the combination demonstrated improved median survival of 29, 30 and 37 days, respectively. The combination treatment prolonged median survival when compared with single drug treatment and  decreased tumor burden. The tumor targeting liposomal-based SGT-53 nanoparticle is capable of sensitizing pancreatic cancer to conventional chemotherapy in pancreatic cancer models. This approach has the potential to be translated into a new, more effective therapy for pancreatic cancer. Further optimization is ongoing, moving towards a Phase 1B/2 clinical trial.Cancer Gene Therapy advance online publication, 8 March 2013; doi:10.1038/cgt.2013.9.

 

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[40]

TÍTULO / TITLE:  - MAZ-binding G4-decoy with locked nucleic acid and twisted intercalating nucleic acid modifications suppresses KRAS in pancreatic cancer cells and delays tumor growth in mice.

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

REVISTA / JOURNAL:  - Nucleic Acids Res. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1093/nar/gkt127

AUTORES / AUTHORS:  - Cogoi S; Zorzet S; Rapozzi V; Geci I; Pedersen EB; Xodo LE

INSTITUCIÓN / INSTITUTION:  - Department of Medical and Biological Sciences, School of Medicine, P.le Kolbe 4,  33100 Udine, Italy, Department of Life Science, University of Trieste, Via Giorgieri 7-9, 34100 Trieste, Italy and Nucleic Acid Center, Institute of Physics, Chemistry and Pharmacy University of Southern Denmark, DK-5230 Odense M, Denmark.

RESUMEN / SUMMARY:  - KRAS mutations are primary genetic lesions leading to pancreatic cancer. The promoter of human KRAS contains a nuclease-hypersensitive element (NHE) that can  fold in G4-DNA structures binding to nuclear proteins, including MAZ (myc-associated zinc-finger). Here, we report that MAZ activates KRAS transcription. To knockdown oncogenic KRAS in pancreatic cancer cells, we designed oligonucleotides that mimic one of the G-quadruplexes formed by NHE (G4-decoys). To increase their nuclease resistance, two locked nucleic acid (LNA) modifications were introduced at the 3’-end, whereas to enhance the folding and stability, two polycyclic aromatic hydrocarbon units (TINA or AMANY) were inserted internally, to cap the quadruplex. The most active G4-decoy (2998), which had two para-TINAs, strongly suppressed KRAS expression in Panc-1 cells. It also repressed their metabolic activity (IC50 = 520 nM), and it inhibited cell growth and colony formation by activating apoptosis. We finally injected 2998 and control oligonucleotides 5153, 5154 (2 nmol/mouse) intratumorally in SCID mice bearing a Panc-1 xenograft. After three treatments, 2998 reduced tumor xenograft  growth by 64% compared with control and increased the Kaplan-Meier median survival time by 70%. Together, our data show that MAZ-specific G4-decoys mimicking a KRAS quadruplex are promising for pancreatic cancer therapy.

 

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[41]

TÍTULO / TITLE:  - Risk factors for pancreatic ductal adenocarcinoma specifically stimulate pancreatic duct glands in mice.

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

REVISTA / JOURNAL:  - Am J Pathol. 2013 Mar;182(3):965-74. doi: 10.1016/j.ajpath.2012.11.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2012.11.016

AUTORES / AUTHORS:  - Bobrowski A; Spitzner M; Bethge S; Mueller-Graf F; Vollmar B; Zechner D

INSTITUCIÓN / INSTITUTION:  - Institute for Experimental Surgery, University of Rostock, Rostock, Germany.

RESUMEN / SUMMARY:  - Diabetes mellitus type 2 and chronic pancreatitis are regarded as risk factors for pancreatic cancer. Pancreatic duct glands (PDGs) were recently described as a new compartment of the major duct in humans and mice. To evaluate the influence of diabetes and chronic pancreatitis on PDGs, cerulein was injected i.p., repetitively over 10 weeks, in mice exhibiting obesity and a type 2 diabetes-like syndrome (B6.V-Lep(ob/ob)) and in lean littermates. By using 5-bromo-2’-deoxyuridine (BrdU), a label-retaining cell population was characterized in PDGs. Cerulein administration led to more BrdU(+) cells in PDGs  of obese mice compared with lean mice. The observed increase was specific to PDGs, because BrdU incorporation in cells of the pancreatic duct was not increased. In addition, the expression of distinct tumor markers in PDGs was characterized by Muc5ac, S100P, regenerating islet-derived 3beta, 14-3-3 sigma, and prostate stem cell antigen immunochemistry. Type 2 diabetes-like syndrome, accompanied by chronic pancreatitis, enhanced nuclear localization of S100P. Both risk factors for pancreatic cancer also induced the production of Muc5ac and the  nuclear localization of S100P. These results demonstrate that diabetes and chronic pancreatitis jointly enhance BrdU incorporation and production of pancreatic cancer-specific proteins in PDGs. The observed alterations suggest that pancreatic tumors might originate from the newly discovered histomorphological structures, called PDGs, which could represent a target for future anticancer therapies.

 

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[42]

TÍTULO / TITLE:  - Update on the role of somatostatin analogs for the treatment of patients with gastroenteropancreatic neuroendocrine tumors.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):56-68. doi: 10.1053/j.seminoncol.2012.11.006.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.006

AUTORES / AUTHORS:  - Toumpanakis C; Caplin ME

INSTITUCIÓN / INSTITUTION:  - Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK.

RESUMEN / SUMMARY:  - Somatostatin analogs (SA) are the standard of care for controlling symptoms of patients with functional gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). SA control symptoms in more than 70% of patients with carcinoid syndrome. Similar results are obtained in patients with functional, hormone-secreting, pancreatic NETs. The use of SA as antiproliferative agents has been established only recently. Retrospective studies have shown stabilization of tumor growth in >50% of patients with progressive disease. The results of a recent randomized phase III trial (PROMID) demonstrated that the median time to progression in patients with midgut carcinoid tumors treated with octreotide LAR  (Long-Acting-Repeatable, Novartis, Basel, Switzerland) was more than twice as long compared to that of patients treated with placebo. The results of a phase III study of lanreotide versus placebo in nonfunctional NETs are not yet available. More studies are needed to determine whether combining SA with novel targeted treatments will result in enhanced antiproliferative activity compared to treatment with a SA alone. Studies are ongoing using pan-receptor agonists (eg, pasireotide) and chimeric dimers, which possess features of somatostatin and dopamine agonists (dopastatins) and are thought to enhance symptom control by binding multiple receptors (somatostatin and dopamine receptors). Somatostatin receptor antagonists are also currently being developed for clinical use. Peptide receptor radionuclide therapy (PRRT), consisting of yttrium-90 and lutetium-177 isotopes conjugated with SA appear to be efficacious in advanced NETs. Randomized studies are needed to definitively establish the safety and efficacy of this strategy compared to other available treatments, and to determine which radiolabeled isotopes or combinations are most effective.

 

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[43]

TÍTULO / TITLE:  - Erlotinib prolongs survival in pancreatic cancer by blocking gemcitabine-induced  MAPK signals.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Apr 1;73(7):2221-34. doi: 10.1158/0008-5472.CAN-12-1453. Epub 2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-1453

AUTORES / AUTHORS:  - Miyabayashi K; Ijichi H; Mohri D; Tada M; Yamamoto K; Asaoka Y; Ikenoue T; Tateishi K; Nakai Y; Isayama H; Morishita Y; Omata M; Moses HL; Koike K

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Gastroetnterology and Molecular Pathology,  Graduate School of Medicine, Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo; Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba; Yamanashi Prefectural Hospital Organization, Yamanashi, Japan; and Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, Tennessee.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers worldwide. Although many regimens have been used for PDAC treatment, the combination of the EGF receptor (EGFR) inhibitor erlotinib with gemcitabine has been the only molecular-targeted drug tested so far that has been superior to gemcitabine alone. The mechanism underlying this effective combinational regimen  remains unknown. Here, we show that the combination is superior to gemcitabine alone in blocking progression and prolonging survival in a murine model of PDAC (Kras activation with Tgfbr2 knockout). We found that gemcitabine induced mitogen-activated protein kinase signaling, which was dramatically inhibited by erlotinib even in the Kras-activated PDAC cells in the mouse model. Mechanistic investigations suggested that gemcitabine induces EGFR ligand expression and ERBB2 activation by increasing heterodimer formation with EGFR, thereby maintaining high levels of ERBB2 protein in PDAC cells. Overall, our findings suggest a significant role of ERBB in PDAC treatment. Cancer Res; 73(7); 2221-34. ©2013 AACR.

 

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[44]

TÍTULO / TITLE:  - Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Mar 14. doi: 10.1038/bjc.2013.108.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.108

AUTORES / AUTHORS:  - Eto K; Kawakami H; Kuwatani M; Kudo T; Abe Y; Kawahata S; Takasawa A; Fukuoka M; Matsuno Y; Asaka M; Sakamoto N

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.

RESUMEN / SUMMARY:  - Background:Pancreatic ductal carcinoma (PDC) is one of the most lethal human carcinomas. Expression patterns of some genes may predict gemcitabine (GEM) treatment efficacy. We examined predictive indicators of survival in GEM-treated  patients by quantifying the expression of several genes in pre-treatment endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples from patients with PDC.Methods:The expressions of human equilibrative nucleoside transporter 1 (hENT1), deoxycitidine kinase, ribonucleoside reductase 1, ribonucleoside reductase 2 and Notch3 in EUS-FNA tissue samples from 71 patients  with unresectable PDC were quantified using real-time reverse transcription-polymerase chain reactions and examined for correlations with GEM sensitivity.Results:The log-rank test detected no significant differences in overall survival between GEM-treated patients with low and high mRNA levels of all genes examined. However, low Notch3 mRNA expression was significantly associated with longer overall survival in a multivariate analysis for survival (P=0.0094). High hENT1 expression level was significantly associated with a longer time to progression (P=0.039). Interaction tests for GEM administration and hENT1 or Notch3 mRNA expression were statistically significant (P=0.0054 and  0.0047, respectively).Conclusion:hENT1 and Notch3 mRNA expressions in EUS-FNA specimens were the key predictive biomarkers of GEM effect and GEM sensitivity in patients with unresectable PDC.British Journal of Cancer advance online publication, 14 March 2013; doi:10.1038/bjc.2013.108 www.bjcancer.com.

 

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[45]

TÍTULO / TITLE:  - Growth inhibition of pancreatic cancer cells by Histone Deacetylase inhibitor belinostat through suppression of multiple pathways including HIF, NFkB, and mTOR signaling in vitro and in vivo.

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

REVISTA / JOURNAL:  - Mol Carcinog. 2013 Mar 8. doi: 10.1002/mc.22024.

            ●● Enlace al texto completo (gratuito o de pago) 1002/mc.22024

AUTORES / AUTHORS:  - Chien W; Lee DH; Zheng Y; Wuensche P; Alvarez R; Wen DL; Aribi AM; Thean SM; Doan NB; Said JW; Koeffler HP

INSTITUCIÓN / INSTITUTION:  - Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma is a devastating disease with few therapeutic options. Histone deacetylase inhibitors are a novel therapeutic approach to cancer treatment; and two new pan-histone deacetylase inhibitors (HDACi), belinostat and panobinostat, are undergoing clinical trials for advanced hematologic malignancies, non-small cell lung cancers and advanced ovarian epithelial cancers. We found that belinostat and panobinostat potently inhibited, in a dose-dependent manner, the growth of six (AsPc1, BxPc3, Panc0327, Panc0403,  Panc1005, MiaPaCa2) of 14 human pancreatic cancer cell lines. Belinostat increased the percentage of apoptotic pancreatic cancer cells and caused prominent G2 /M growth arrest of most pancreatic cancer cells. Belinostat prominently inhibited PI3K-mTOR-4EBP1 signaling with a 50% suppression of phorphorylated 4EBP1 (AsPc1, BxPc3, Panc0327, Panc1005 cells). Surprisingly, belinostat profoundly blocked hypoxia signaling including the suppression of hypoxia response element reporter activity; as well as an approximately 10-fold decreased transcriptional expression of VEGF, adrenomedullin, and HIF1alpha at 1% compared to 20% O2 . Treatment with this HDACi decreased levels of thioredoxin mRNA associated with increased levels of its endogenous inhibitor thioredoxin binding protein-2. Also, belinostat alone and synergistically with gemcitabine significantly (P = 0.0044) decreased the size of human pancreatic tumors grown in immunodeficiency mice. Taken together, HDACi decreases growth, increases apoptosis, and is associated with blocking the AKT/mTOR pathway. Surprisingly, it blocked hypoxic growth related signals. Our studies of belinostat suggest it may  be an effective drug for the treatment of pancreatic cancers when used in combination with other drugs such as gemcitabine. © 2013 Wiley Periodicals, Inc.

 

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[46]

TÍTULO / TITLE:  - Cost-Utility Estimations of Palliative Care in Patients With Pancreatic Adenocarcinoma: A Retrospective Analysis.

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

REVISTA / JOURNAL:  - World J Surg. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00268-013-2003-z

AUTORES / AUTHORS:  - Ljungman D; Hyltander A; Lundholm K

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden.

RESUMEN / SUMMARY:  - BACKGROUND: We earlier reported cost-utility estimates in patients who undergo resection aimed at cure for pancreatic carcinoma. The present study describes similar information on patients with unresectable tumors who experienced palliative care only. METHODS: A population-based cohort of patients with exocrine pancreatic adenocarcinoma during 1998-2005 was evaluated retrospectively (n = 444). Total direct health care costs at departments of surgery and oncology, for primary health care, and at hospice were achieved. Self-estimated health-related quality of life (HRQL) was assessed by the SF-36. A single preference-based utility index, SF-6D, was derived from SF-36 items to estimate quality-adjusted life years (QALYs). Results were compared to similar findings in a previously reported group of patients with pancreatic carcinoma resected for cure (n = 31). RESULTS: Palliative care patients (n = 305) had impaired HRQL particularly related to physical domains. The mean preference-based health utility index at diagnosis was 0.65 +/- 0.02 [95 % confidence interval (CI) 0.61-0.69] compared to 0.77 +/- 0.02 (95 % CI 0.75-0.79) in healthy reference individuals. Total direct health care costs were 50 % in patients on palliative care compared to costs for surgical R0 resections (23,701 and 50,950<euro>, respectively). QALYs for 1 year from diagnosis were 0.2 (95 % CI 0.17-0.23) in patients on palliative care and 0.48 (95 % CI 0.44-0.54) in resection patients. Costs per QALY were 118,418<euro> and 106,146<euro>, respectively (95 % CI 103,048-139,418<euro> and 94,352-115,795<euro>). CONCLUSIONS: Optimized palliative care of patients with exocrine pancreatic carcinoma had costs per achieved utility similar to those for surgical resections aimed at cure.

 

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[47]

TÍTULO / TITLE:  - FDG PET or PET/CT in patients with pancreatic cancer: when does it add to diagnostic CT or MRI?

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

REVISTA / JOURNAL:  - Clin Imaging. 2013 Mar;37(2):295-301. doi: 10.1016/j.clinimag.2012.07.005. Epub 2012 Aug 24.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.07.005

AUTORES / AUTHORS:  - Javery O; Shyn P; Mortele K

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. Electronic address: ojavery@partners.org.

RESUMEN / SUMMARY:  - OBJECTIVE: Assess the impact of FDG-PET or PET/CT (PI) on pancreatic cancer management when added to CT or MRI (CDI). MATERIALS AND METHODS: Forty-nine patients underwent 79 PI exams. Discordant findings on PI and CDI were assessed for clinical impact. RESULTS: Fifteen of 79 PI-CDI pairs were discordant. Ten of  79 PI favorably and 5 of 79 unfavorably altered management. PI favorably altered  management more often when ordered for therapy monitoring compared to staging [risk ratio 13.00 (95% CI 1.77-95.30)] or restaging [risk ratio 18.5 (95% CI 2.50-137.22)]. CONCLUSION: PI favorably alters management more often when used for therapy monitoring compared to staging or restaging.

 

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[48]

TÍTULO / TITLE:  - Risk Factors for Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas:  A Multicentre Case-Control Study.

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

REVISTA / JOURNAL:  - Am J Gastroenterol. 2013 Mar 5. doi: 10.1038/ajg.2013.42.

            ●● Enlace al texto completo (gratuito o de pago) 1038/ajg.2013.42

AUTORES / AUTHORS:  - Capurso G; Boccia S; Salvia R; Del Chiaro M; Frulloni L; Arcidiacono PG; Zerbi A; Manta R; Fabbri C; Ventrucci M; Tarantino I; Piciucchi M; Carnuccio A; Boggi U; Leoncini E; Costamagna G; Delle Fave G; Pezzilli R; Bassi C; Larghi A

INSTITUCIÓN / INSTITUTION:  - Digestive and Liver Disease Unit, Faculty of Medicine and Psychology, Sapienza University of Rome at S. Andrea Hospital, Rome, Italy.

RESUMEN / SUMMARY:  - OBJECTIVES:To investigate environmental, personal, and hereditary risk factors associated with the occurrence of intraductal papillary mucinous neoplasms of the pancreas (IPMNs).METHODS:Multicentre case-control study. Risk factors were identified from a questionnaire collecting data on family and medical history, and environmental factors. Cases were prevalent IPMNs seen at the participating units within an 18-month timeframe. Matched controls were enrolled alongside patients seen at outpatient clinics.RESULTS:Three-hundred and ninety patients with IPMN and 390 matched controls (166 males, mean age 65 in each group) were enrolled. Of the IPMNs, 310 had branch-duct involvement and 80 main-duct involvement. The only cancer with a 1st degree family history significantly higher in IPMN was pancreatic ductal adenocarcinoma (PDAC) (5.4% vs. 1.5%). Previous history of diabetes (13.6% vs. 7.5%), chronic pancreatitis (CP) (3.1% vs. 0.3%), peptic ulcer (7.2% vs. 4.3%), and insulin use (4.9% vs. 1.1%) were all more frequent with IPMNs. Logistic regression multivariate analysis revealed that history of diabetes (odds ratio (OR): 1.79, confidence interval (CI) 95%: 1.08-2.98), CP (OR: 10.10, CI 95%: 1.30-78.32), and family histories of PDAC (OR: 2.94, CI 95%: 1.17-7.39) were all independent risk factors. However, when analysis was restricted to diabetics who had taken insulin, risk of IPMN became stronger (OR: 6.03, CI 95%: 1.74-20.84). The association with all these risk factors seemed stronger for the subgroup with main duct involvement.CONCLUSIONS:A previous history of diabetes, especially with insulin use, CP, and family history of PDAC are all relevant risk factors for the development of IPMN. These results  suggest an overlap between certain risk factors for PDAC and IPMN.Am J Gastroenterol advance online publication, 5 March 2013; doi:10.1038/ajg.2013.42.

 

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[49]

TÍTULO / TITLE:  - Phase I/II study of albumin-bound nab-paclitaxel plus gemcitabine administered to Chinese patients with advanced pancreatic cancer.

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

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Apr;71(4):1065-72. doi: 10.1007/s00280-013-2102-4. Epub 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2102-4

AUTORES / AUTHORS:  - Zhang DS; Wang DS; Wang ZQ; Wang FH; Luo HY; Qiu MZ; Wang F; Li YH; Xu RH

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Oncology in South China, Department of Medical Oncology,  Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China.

RESUMEN / SUMMARY:  - PURPOSE: The primary objective of this study was to evaluate the dose-limiting toxicities (DLTs) and identify the maximum-tolerated dose (MTD) and recommended dose of nab-paclitaxel plus gemcitabine as a first-line treatment in Chinese patients with advanced pancreatic ductal adenocarcinoma (PDA). METHODS: Patients  with previously untreated advanced PDA were treated with nab-paclitaxel followed  by gemcitabine (1,000 mg/m(2)) administered intravenously for 30 min on days 1 and 8 and repeated every 21 days. RESULTS: Patients received nab-paclitaxel at the following dose levels: 80 mg/m(2) (n = 3), 100 mg/m(2) (n = 6), and 120 mg/m(2) (n = 12). The DLTs evaluated were elevated alanine aminotransferase and febrile neutropenia. However, there had no two out of three to six patients experienced DLTs, the MTD was not met. A total of 93 cycles were administered. The most common grade ¾ toxicities were neutropenia (9.52 %), thrombocytopenia  (4.76 %), and sensory neuropathy (4.76 %). For 12 patients receiving 120 mg/m(2), the overall response rate and disease control rate were 41.67 and 83.33 %, respectively, and the median progression-free survival and overall survival were  5.23 and 12.17 months, respectively. CONCLUSIONS: Treatment with albumin-bound nab-paclitaxel (120 mg/m(2)) plus gemcitabine has a favorable safety profile with an encouraging antitumor effect in Chinese patients.

 

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[50]

TÍTULO / TITLE:  - Toxicity study of gemcitabine, oxaliplatin, and bevacizumab, followed by 5-fluorouracil, oxaliplatin, bevacizumab, and radiotherapy, in patients with locally advanced pancreatic cancer.

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

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2147-4

AUTORES / AUTHORS:  - Sohal DP; Metz JM; Sun W; Giantonio BJ; Plastaras JP; Ginsberg G; Kochman ML; Teitelbaum UR; Harlacker K; Heitjan DF; Feldman MD; Drebin JA; O’Dwyer PJ

INSTITUCIÓN / INSTITUTION:  - Cleveland Clinic, Taussig Cancer Institute, 9500 Euclid Avenue, R35, Cleveland, OH, 44195, USA, sohald@ccf.org.

RESUMEN / SUMMARY:  - PURPOSE: Platinum compounds or bevacizumab, in combination with gemcitabine, achieved good response rates in early studies in advanced pancreatic cancer. This prompted an evaluation of an aggressive approach to allow better local control and resectability in locally advanced disease. METHODS: We piloted a combination  of gemcitabine/oxaliplatin/bevacizumab Q2w for four cycles, followed by oxaliplatin and bevacizumab added to infusional 5-FU and radiotherapy, in patients with locally advanced pancreatic cancer. RESULTS: Nineteen patients were treated, of whom 17 completed the protocol-specified treatment. Median age was 60 years. Fifteen had unresectable, and four had borderline resectable disease. Toxicity of chemotherapy was moderate: grade III neutropenia (5) and grade I/II nausea, vomiting, fatigue, and neuropathy. During chemoradiation, major grade III toxicities were nausea and vomiting (3 each). One patient had intractable pain early on, necessitating treatment cessation. Response rate for 18 evaluable patients was 11 % (by RECIST); five patients (4 inoperable, 1 borderline, 26 %) went on to have surgery. One-year overall survival was 58 % and progression-free  survival was 37 %. CONCLUSIONS: This combination, associated with higher response rates in metastatic disease, had a lower than expected response rate in primary tumors. Although tolerable, our approach failed to affect clinical outcomes meaningfully.

 

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[51]

TÍTULO / TITLE:  - New Syndrome of Paraganglioma and Somatostatinoma Associated With Polycythemia.

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.47.1912

AUTORES / AUTHORS:  - Pacak K; Jochmanova I; Prodanov T; Yang C; Merino MJ; Fojo T; Prchal JT; Tischler AS; Lechan RM; Zhuang Z

INSTITUCIÓN / INSTITUTION:  - Karel Pacak, Ivana Jochmanova, and Tamara Prodanov, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Maria J. Merino and Tito Fojo, National Cancer Institute; Chunzhang Yang and Zhengping Zhuang, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Josef T. Prchal, University of Utah School of Medicine and  VA Hospital, Salt Lake City, UT; and Arthur S. Tischler and Ronald M. Lechan, Tufts Medical Center, Boston, MA.

RESUMEN / SUMMARY:  - PURPOSEThe occurrence of >/= two distinct types of tumors, one of them paraganglioma (PGL), is unusual in an individual patient, except in hereditary cancer syndromes. PATIENTS AND METHODSFour unrelated patients were investigated,  with thorough clinical evaluation. Plasma and tissue catecholamines and metanephrines were measured by high-performance liquid chromatography. Anatomic and functional imaging were performed for tumor visualization. Germline and tumor tissue DNA were analyzed for hypoxia-inducible factor 2 alpha (HIF2A) mutations.  The prolyl hydroxylation and stability of the mutant HIF2alpha protein, transcriptional activity of mutant HIF2A, and expression of hypoxia-related genes were also investigated. Immunohistochemical staining for HIF1/2alpha was performed on formalin-fixed, paraffin-embedded tumor tissue.ResultsPatients were  found to have polycythemia, multiple PGLs, and duodenal somatostatinomas by imaging or biochemistry with somatic gain-of-function HIF2A mutations. Each patient carried an identical unique mutation in both types of tumors but not in germline DNA. The HIF2A mutations in these patients were clustered adjacent to an oxygen-sensing proline residue, affecting HIF2alpha interaction with the prolyl hydroxylase domain 2-containing protein, decreasing the hydroxylation of HIF2alpha, and reducing HIF2alpha affinity for the von Hippel-Lindau protein and  its degradation. An increase in the half-life of HIF2alpha was associated with upregulation of the hypoxia-related genes EPO, VEGFA, GLUT1, and END1 in tumors.  CONCLUSIONOur findings indicate the existence of a new syndrome with multiple PGLs and somatostatinomas associated with polycythemia. This new syndrome results from somatic gain-of-function HIF2A mutations, which cause an upregulation of hypoxia-related genes, including EPO and genes important in cancer biology.

 

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[52]

TÍTULO / TITLE:  - Differences in the pattern of structural abnormalities on CT in patients with cystic fibrosis and pancreatic sufficiency or insufficiency.

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

REVISTA / JOURNAL:  - Chest. 2013 Feb 7. doi: 10.1378/chest.12-1226.

            ●● Enlace al texto completo (gratuito o de pago) 1378/chest.12-1226

AUTORES / AUTHORS:  - Simanovsky N; Cohen-Cymberknoh M; Shoseyov D; Gileles-Hillel A; Wilschanski M; Kerem E; Hiller N

INSTITUCIÓN / INSTITUTION:  - Dr. Simanovsky and Dr. Cohen-Cymberknoh contributed equally to the preparation of this manuscript.

RESUMEN / SUMMARY:  - ABSTRACT BACKGROUND Cystic fibrosis (CF) genotypes characterized by pancreatic sufficiency (CF-PS) are generally associated with milder disease versus those with pancreatic insufficiency (CF-PI); however, the correlation between pancreatic status and type and severity of structural lung changes has not been studied. We aimed to evaluate differences in the severity and distribution of pulmonary manifestations of CF, in patients with PS vs PI. METHODS We retrospectively evaluated changes in individual lobes and in the whole lung on chest CT using the modified Brody score in 84 CF patients (39 females, 45 males;  ages 4-68 years, mean 20.5) treated from 2000-2010. Our IRB waived the requirement for informed consent. The severity of lung changes and distribution of pulmonary disease were compared for 28 patients with CF-PS and 56 with CF-PI using the Student’s t-test, nonparametric Pearson chi-square, or mixed-design ANOVA. Correlations were evaluated with the Pearson (continuous variables) or Spearman’s rho (nonparametric variables) tests. A linear regression model was used for multivariate analyses. RESULTS In comparison to patients with CF-PS, those with CF-PI had more severe lung disease (p=0.001) with predominant upper lobe involvement (p=0.002), and significant differences in Brody scores for bronchiectasis and bronchial wall thickening. Lung manifestations in patients with CF-PS did not show predominant involvement of any one area (p=0.133). CONCLUSIONS In patients with CF-PI, structural lung changes are more severe with  upper lobe predominance, prominent bronchiectasis, and bronchial wall thickening  versus lower severity and more general distribution of changes in those with CF-PS.

 

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[53]

TÍTULO / TITLE:  - Comparative proteomic and phosphoproteomic profiling of pancreatic adenocarcinoma cells treated with CB1 or CB2 agonists.

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

REVISTA / JOURNAL:  - Electrophoresis. 2013 Mar 6. doi: 10.1002/elps.201200402.

            ●● Enlace al texto completo (gratuito o de pago) 1002/elps.201200402

AUTORES / AUTHORS:  - Brandi J; Dando I; Palmieri M; Donadelli M; Cecconi D

INSTITUCIÓN / INSTITUTION:  - Department of Biotechnology, Proteomics and Mass Spectrometry Laboratory.

RESUMEN / SUMMARY:  - The pancreatic adenocarcinoma cell line Panc1 was treated with cannabinoid receptor ligands (ACPA or GW405833) in order to elucidate the molecular mechanism of their anticancer effect. A proteomic approach was used to analyse the protein  and phosphoprotein profiles. Western blot and functional data mining were also employed in order to validate results, classify proteins, and explore their potential relationships. We demonstrated that the two cannabinoids act through a  widely common mechanism involving up and down-regulation of proteins related to energetic metabolism and cell growth regulation. Overall, the results reported might contribute to the development of a therapy based on cannabinoids for pancreatic adenocarcinoma.

 

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[54]

TÍTULO / TITLE:  - Structure-Based Design and Evaluation of Naphthalene Diimide G-Quadruplex Ligands As Telomere Targeting Agents in Pancreatic Cancer Cells.

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

REVISTA / JOURNAL:  - J Med Chem. 2013 Apr 2.

            ●● Enlace al texto completo (gratuito o de pago) 1021/jm301899y

AUTORES / AUTHORS:  - Micco M; Collie GW; Dale AG; Ohnmacht SA; Pazitna I; Gunaratnam M; Reszka AP; Neidle S

INSTITUCIÓN / INSTITUTION:  - The School of Pharmacy, University College London, London WC1N 1AX, U.K.

RESUMEN / SUMMARY:  - Tetra-substituted naphthalene diimide (ND) derivatives with positively charged termini are potent stabilizers of human telomeric and gene promoter DNA quadruplexes and inhibit the growth of human cancer cells in vitro and in vivo. The present study reports the enhancement of the pharmacological properties of earlier ND compounds using structure-based design. Crystal structures of three complexes with human telomeric intramolecular quadruplexes demonstrate that two of the four strongly basic N-methyl-piperazine groups can be replaced by less basic morpholine groups with no loss of intermolecular interactions in the grooves of the quadruplex. The new compounds retain high affinity to human telomeric quadruplex DNA but are 10-fold more potent against the MIA PaCa-2 pancreatic cancer cell line, with IC50 values of approximately 10 nM. The lead compound induces cellular senescence but does not inhibit telomerase activity at  the nanomolar dosage levels required for inhibition of cellular proliferation. Gene array qPCR analysis of MIA PaCa-2 cells treated with the lead compound revealed significant dose-dependent modulation of a distinct subset of genes, including strong induction of DNA damage responsive genes CDKN1A, DDIT3, GADD45A/G, and PPM1D, and repression of genes involved in telomere maintenance, including hPOT1 and PARP1.

 

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[55]

TÍTULO / TITLE:  - Is it necessary to follow patients after resection of a benign pancreatic intraductal papillary mucinous neoplasm?

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

REVISTA / JOURNAL:  - J Am Coll Surg. 2013 Apr;216(4):657-65. doi: 10.1016/j.jamcollsurg.2012.12.026. Epub 2013 Feb 6.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jamcollsurg.2012.12.026

AUTORES / AUTHORS:  - He J; Cameron JL; Ahuja N; Makary MA; Hirose K; Choti MA; Schulick RD; Hruban RH; Pawlik TM; Wolfgang CL

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD.

RESUMEN / SUMMARY:  - BACKGROUND: Little is known about the risk of subsequently developing a new or progressive intraductal papillary mucinous neoplasm (IPMN) after partial pancreatic resection of a noninvasive IPMN. STUDY DESIGN: One hundred thirty patients with more than 1 year of follow-up after resection were included in this analysis. RESULTS: At a median follow-up of 38 months, 22 (17%) developed imaging evidence of a new or progressive IPMN. Eleven (8%) underwent completion resection. Three of the 11 patients had invasive adenocarcinoma. Two other patients developed metastatic pancreatic adenocarcinoma and did not undergo resection. All 5 patients (4%) with cancer had negative margins at initial operation. Sixteen of 100 patients (16%) with negative margins for IPMN at the initial operation developed a new IPMN vs 6 of 30 patients (20%) with margins positive for IPMN (p = ns). Five of 22 patients (23%) with a new IPMN had a family history of pancreatic cancer, while 8 of 108 patients (7%) without a new IPMN had a family history (p < 0.05). Overall, the chances of developing a new IPMN at 1, 5, and 10 years after the initial surgery were 4%, 25%, and 62%, respectively, and of requiring surgery were 1.6%, 14%, and 18%, respectively. The estimated chances of developing invasive pancreatic cancer were 0%, 7%, and 38% at 1, 5, and 10 years, respectively. CONCLUSIONS: Patients who have undergone resection for noninvasive IPMN require indefinite close surveillance because of the risks of developing a new IPMN, of requiring surgery, and of developing cancer. A family history of pancreatic cancer, but not margin status or degree of dysplasia, is associated with a risk of development of a new or progressive IPMN.

 

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[56]

TÍTULO / TITLE:  - Palladin promotes invasion of pancreatic cancer cells by enhancing invadopodia formation in cancer-associated fibroblasts.

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

REVISTA / JOURNAL:  - Oncogene. 2013 Mar 25. doi: 10.1038/onc.2013.68.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.68

AUTORES / AUTHORS:  - Goicoechea SM; Garcia-Mata R; Staub J; Valdivia A; Sharek L; McCulloch CG; Hwang RF; Urrutia R; Yeh JJ; Kim HJ; Otey CA

INSTITUCIÓN / INSTITUTION:  - Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

RESUMEN / SUMMARY:  - The stromal compartment surrounding epithelial-derived pancreatic tumors is thought to have a key role in the aggressive phenotype of this malignancy. Emerging evidence suggests that cancer-associated fibroblasts (CAFs), the most abundant cells in the stroma of pancreatic tumors, contribute to the tumor’s invasion, metastasis and resistance to therapy, but the precise molecular mechanisms that regulate CAFs behavior are poorly understood. In this study, we utilized immortalized human pancreatic CAFs to investigate molecular pathways that control the matrix-remodeling and invasion-promoting activity of CAFs. We showed previously that palladin, an actin-associated protein, is expressed at high levels in CAFs of pancreatic tumors and other solid tumors, and also in an immortalized line of human CAFs. In this study, we found that short-term exposure of CAFs to phorbol esters reduced the number of stress fibers and triggered the appearance of individual invadopodia and invadopodial rosettes in CAFs. Molecular analysis of invadopodia revealed that their composition resembled that of similar structures (that is, invadopodia and podosomes) described in other cell types. Pharmacological inhibition and small interfering RNA knockdown experiments demonstrated that protein kinase C, the small GTPase Cdc42 and palladin were necessary for the efficient assembly of invadopodia by CAFs. In addition, GTPase  activity assays showed that palladin contributes to the activation of Cdc42. In mouse xenograft experiments using a mixture of CAFs and tumor cells, palladin expression in CAFs promoted the rapid growth and metastasis of human pancreatic tumor cells. Overall, these results indicate that high levels of palladin expression in CAFs enhance their ability to remodel the extracellular matrix by regulating the activity of Cdc42, which in turn promotes the assembly of matrix-degrading invadopodia in CAFs and tumor cell invasion. Together, these results identify a novel molecular signaling pathway that may provide new molecular targets for the inhibition of pancreatic cancer metastasis.Oncogene advance online publication, 25 March 2013; doi:10.1038/onc.2013.68.

 

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[57]

TÍTULO / TITLE:  - Macrophage scavenger receptor a promotes tumor progression in murine models of ovarian and pancreatic cancer.

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

REVISTA / JOURNAL:  - J Immunol. 2013 Apr 1;190(7):3798-805. doi: 10.4049/jimmunol.1203194. Epub 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 4049/jimmunol.1203194

AUTORES / AUTHORS:  - Neyen C; Pluddemann A; Mukhopadhyay S; Maniati E; Bossard M; Gordon S; Hagemann T

INSTITUCIÓN / INSTITUTION:  - Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.

RESUMEN / SUMMARY:  - Alternatively activated macrophages express the pattern recognition receptor scavenger receptor A (SR-A). We demonstrated previously that coculture of macrophages with tumor cells upregulates macrophage SR-A expression. We show in this study that macrophage SR-A deficiency inhibits tumor cell migration in a coculture assay. We further demonstrate that coculture of tumor-associated macrophages and tumor cells induces secretion of factors that are recognized by SR-A on tumor-associated macrophages. We tentatively identified several potential ligands for the SR-A receptor in tumor cell-macrophage cocultures by mass spectrometry. Competing with the coculture-induced ligand in our invasion assay recapitulates SR-A deficiency and leads to similar inhibition of tumor cell invasion. In line with our in vitro findings, tumor progression and metastasis are inhibited in SR-A(-/-) mice in two in vivo models of ovarian and pancreatic cancer. Finally, treatment of tumor-bearing mice with 4F, a small peptide SR-A ligand able to compete with physiological SR-A ligands in vitro, recapitulates the inhibition of tumor progression and metastasis observed in SR-A(-/-) mice. Our observations suggest that SR-A may be a potential drug target in the prevention of metastatic cancer progression.

 

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[58]

TÍTULO / TITLE:  - Sirtuin-1 Regulates Acinar-to-Ductal Metaplasia and Supports Cancer Cell Viability in Pancreatic Cancer.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Apr 1;73(7):2357-2367. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3359

AUTORES / AUTHORS:  - Wauters E; Sanchez-Arevalo Lobo VJ; Pinho AV; Mawson A; Herranz D; Wu J; Cowley MJ; Colvin EK; Njicop EN; Sutherland RL; Liu T; Serrano M; Bouwens L; Real FX; Biankin AV; Rooman I

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Cancer Research Program, Garvan Institute of Medical Research, Sydney, Australia; Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium; St Vincent’s Clinical School, University New South Wales, Australia; Programa de Patologia Molecular and Programa de Oncologia Molecular, CNIO (Spanish National Cancer Research Center), Madrid, España; Children’s Cancer Institute Australia for Medical Research, Randwick, Australia;  and Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, España.

RESUMEN / SUMMARY:  - The exocrine pancreas can undergo acinar-to-ductal metaplasia (ADM), as in the case of pancreatitis where precursor lesions of pancreatic ductal adenocarcinoma  (PDAC) can arise. The NAD+-dependent protein deacetylase Sirtuin-1 (Sirt1) has been implicated in carcinogenesis with dual roles depending on its subcellular localization. In this study, we examined the expression and the role of Sirt1 in  different stages of pancreatic carcinogenesis, i.e. ADM models and established PDAC. In addition, we analyzed the expression of KIAA1967, a key mediator of Sirt1 function, along with potential Sirt1 downstream targets. Sirt1 was co-expressed with KIAA1967 in the nuclei of normal pancreatic acinar cells. In ADM, Sirt1 underwent a transient nuclear-to-cytoplasmic shuttling. Experiments where during ADM, we enforced repression of Sirt1 shuttling, inhibition of Sirt1  activity or modulation of its expression, all underscore that the temporary decrease of nuclear and increase of cytoplasmic Sirt1 stimulate ADM. Our results  further underscore that important transcriptional regulators of acinar differentiation, that is, Pancreatic transcription factor-1a and beta-catenin can be deacetylated by Sirt1. Inhibition of Sirt1 is effective in suppression of ADM  and in reducing cell viability in established PDAC tumors. KIAA1967 expression is differentially downregulated in PDAC and impacts on the sensitivity of PDAC cells to the Sirt1/2 inhibitor Tenovin-6. In PDAC, acetylation of beta-catenin is not affected, unlike p53, a well-characterized Sirt1-regulated protein in tumor cells. Our results reveal that Sirt1 is an important regulator and potential therapeutic target in pancreatic carcinogenesis. Cancer Res; 73(7); 2357-67. ©2012 AACR.

 

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[59]

TÍTULO / TITLE:  - PARI overexpression promotes genomic instability and pancreatic tumorigenesis.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3313

AUTORES / AUTHORS:  - O’Connor KW; Dejsuphong D; Park E; Nicolae CM; Kimmelman AC; D’Andrea AD; Moldovan GL

INSTITUCIÓN / INSTITUTION:  - Dept. Radiation Oncology, Dana-Farber Cancer Institute.

RESUMEN / SUMMARY:  - Treatment options for patients with pancreatic ductal adenocarcinoma remain limited. Therapeutic targets of interest include mutated molecules that predispose to pancreatic cancer such as KRAS and TP53. Here we show that an element of the homologous recombination pathway of DNA repair, the PARP-binding protein C12orf48/PARI (PARPBP), is overexpressed specifically in pancreatic cancer cells where it is an appealing candidate for targeted therapy. PARI upregulation in pancreatic cancer cells or avian DT40 cells conferred DNA repair  deficiency and genomic instability. Significantly, PARI silencing compromised cancer cell proliferation in vitro, leading to cell cycle alterations associated  with S phase delay, perturbed DNA replication and activation of the DNA damage response pathway in the absence of DNA damage stimuli. Conversely, PARI overexpression produced tolerance to DNA damage by promoting replication of damaged DNA. In a mouse xenograft model of pancreatic cancer, PARI silencing was  sufficient to reduce pancreatic tumor growth in vivo. Taken together, our findings offered a preclinical proof-of-concept for PARI as candidate therapeutic target to treat pancreatic ductal adenocarcinoma.

 

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[60]

TÍTULO / TITLE:  - Metastatic Gastrinoma in a Pediatric Patient With Zollinger-Ellison Syndrome.

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

REVISTA / JOURNAL:  - J Pediatr Hematol Oncol. 2013 Feb 15.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e318282dadf

AUTORES / AUTHORS:  - Massaro SA; Emre SH

INSTITUCIÓN / INSTITUTION:  - *Section of Hematology/Oncology, Department of Pediatrics daggerYale Stem Cell Center, Yale University School of Medicine double daggerSection of Transplantation and Immunology, Department of Surgery section signYale New Haven  Transplant Center, New Haven, CT.

RESUMEN / SUMMARY:  - Metastatic neuroendocrine tumors of childhood are extremely rare, and as such present diagnostic and therapeutic challenges. Here, we report a case of gastrinoma with extensive hepatic metastases in a pediatric patient with Zollinger-Ellison Syndrome who underwent orthotopic liver transplant followed by  cytotoxic chemotherapy, somatostatin analog therapy, and immune modulation.

 

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[61]

TÍTULO / TITLE:  - Risk of pancreatic cancer in breast cancer families from the Breast Cancer Family Registry.

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

REVISTA / JOURNAL:  - Cancer Epidemiol Biomarkers Prev. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1055-9965.EPI-12-0195

AUTORES / AUTHORS:  - Mocci E; Milne RL; Yuste Mendez-Villamil E; Hopper JL; John EM; Andrulis IL; Chung WK; Daly MB; Buys SS; Malats N; Goldgar DE

INSTITUCIÓN / INSTITUTION:  - 1Spanish National Cancer Research Centre (CNIO).

RESUMEN / SUMMARY:  - BACKGROUND: Increased risk of pancreatic cancer (PC) has been reported in breast  cancer (BC) families carrying BRCA1and BRCA2 mutations; however, PC risk in mutation-negative (BRCAX) families has not been explored to date. The aim of this study was to estimate PC risk in high-risk BC families according to the BRCA mutation status. METHODS: A retrospective cohort analysis was applied to estimate standardized incidence ratios (SIR) for PC. A total of 5,799 families with >/=1 BC case tested for mutations in BRCA1 and/or BRCA2 were eligible. Families were divided into four classes: BRCA1, BRCA2, BRCAX with >/=2 BC diagnosed before age  50 (class 3), and the remaining BRCAX families (class 4). RESULTS: BRCA1 mutation carriers were at increased risk of PC (SIR= 4.11; 95% confidence interval [CI], 2.94-5.76) as were BRCA2 mutation carriers (SIR=5.79; 95% CI, 4.28-7.84). BRCAX family members were also at increased PC risk, which did not appear to vary by number of members with early-onset breast cancer (SIR=1.31; 95%CI, 1.06-1.63 for  Class 3 and SIR=1.30; 95%CI, 1.13-1.49 for class 4). CONCLUSIONS: Germline mutations in BRCA1 and BRCA2 are associated with an increased risk of PC. Members of BRCAX families are also at increased risk of PC, pointing to the existence of  other genetic factors that increase the risk of both PC and BC. Impact:This study clarifies the relationship between familial breast cancer and pancreatic cancer.  Given its high mortality, PC should be included in risk assessment in familial breast cancer counseling.

 

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[62]

TÍTULO / TITLE:  - Predictors of Malignancy in Intraductal Papillary Mucinous Neoplasm of the Pancreas: Analysis of 310 Pancreatic Resection Patients at Multiple High-Volume Centers.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31827a7b84

AUTORES / AUTHORS:  - Shimizu Y; Yamaue H; Maguchi H; Yamao K; Hirono S; Osanai M; Hijioka S; Hosoda W; Nakamura Y; Shinohara T; Yanagisawa A

INSTITUCIÓN / INSTITUTION:  - From the *Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya; daggerThe Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama; double daggerCenter for Gastroenterology, Teine-Keijinkai Hospital, Sapporo; Departments of section signGastroenterology and parallelPathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya; paragraph signDepartment of Clinical Laboratory Medicine, Wakayama Medical University, School of Medicine, Wakayama; #Department  of Pathology, Teine-Keijinkai Hospital, Sapporo; and **Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

RESUMEN / SUMMARY:  - OBJECTIVES: The present study was a retrospective investigation of predictors of  malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: The subjects were 310 patients who underwent pancreatic resection at 3 high-volume centers. Preoperative laboratory and imaging findings were analyzed in logistic regression analyses. Endoscopic ultrasonography measurements were essential for the size of mural nodules, and a central review was conducted for pathological diagnosis. RESULTS: Pathological diagnosis was benign IPMN in 150 cases and malignant in 160 (noninvasive carcinoma, n = 100; invasive, n = 60). In multivariate analysis, size of mural nodules, diameter of main pancreatic duct, and cyst size of branch pancreatic duct were independent predictors of malignancy, and areas under the receiver operating characteristic curve for these 3 factors were 0.798, 0.643, and 0.601, respectively. With 7 mm taken as the cutoff value for the size of mural nodules, the diagnosis of malignant IPMN had sensitivity of 74.3% and specificity of 72.7%. Carcinoma without nodules was present in 15 patients (15/160 [9.4%]). CONCLUSIONS: The size of mural nodules measured with endoscopic ultrasonography showed high predictive ability. However, about 10% of carcinoma patients did not have nodules, and the handling of the diagnosis in such cases is a problem for the future.

 

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[63]

TÍTULO / TITLE:  - Gemcitabine plus capecitabine in unselected patients with advanced pancreatic cancer.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Apr;42(3):511-5. doi: 10.1097/MPA.0b013e31826c6aee.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826c6aee

AUTORES / AUTHORS:  - Hubner RA; Worsnop F; Cunningham D; Chau I

INSTITUCIÓN / INSTITUTION:  - From the *Department of Medical Oncology, Christie Hospital Foundation Trust, Manchester; daggerDepartment of Medicine, Royal Marsden Hospital, London, United  Kingdom.

RESUMEN / SUMMARY:  - OBJECTIVES: Gemcitabine in combination with capecitabine (GEMCAP) is a treatment  option for patients with advanced pancreatic cancer (APC), but data are lacking concerning outcomes in unselected patients not enrolled to a randomized trial. METHODS: Baseline demographic, clinical, toxicity, tumor response, and survival data were collected for previously untreated patients with APC receiving off-protocol GEMCAP at a single institution between 2005 and 2009. RESULTS: Data  from 113 patients were included in the study. The mean age was 65 years; 51% of patients had metastatic disease; and 80% were of World Health Organization performance status 0 or 1. Patients received a mean of 20 weeks of chemotherapy.  The objective response rate was 9.7%; the median overall survival was 8.7 months  (95% confidence interval, 6.7-10.7), and 34% of patients were alive 1 year after  starting treatment. Performance status (0 or 1 vs 2) was a significant prognostic factor (P < 0.0001). Grade 3 or 4 adverse events, excluding nonfebrile neutropenia, were experienced by 37 patients (33%), the commonest being lethargy  (8%), hand-foot syndrome (8%), diarrhea (7%), thrombocytopenia (4%), and febrile  neutropenia (6%). CONCLUSIONS: Gemcitabine in combination with capecitabine is effective and tolerable in unselected patients with APC, and outcomes are comparable with those of patients receiving GEMCAP in clinical trials.

 

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[64]

TÍTULO / TITLE:  - Simultaneous 68Ga-DOTATOC PET/MRI in Patients With Gastroenteropancreatic Neuroendocrine Tumors: Initial Results.

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

REVISTA / JOURNAL:  - Invest Radiol. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLI.0b013e3182871a7f

AUTORES / AUTHORS:  - Beiderwellen KJ; Poeppel TD; Hartung-Knemeyer V; Buchbender C; Kuehl H; Bockisch A; Lauenstein TC

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Diagnostic and Interventional Radiology and Neuroradiology, and daggerNuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Essen; and double daggerDepartment of Diagnostic and Interventional Radiology, University of Dusseldorf, Dusseldorf, Germany.

RESUMEN / SUMMARY:  - OBJECTIVES: The aim of this pilot study was to demonstrate the potential of simultaneously acquired 68-Gallium-DOTA-D-Phe1-Tyr-octreotide (Ga-DOTATOC) positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison with Ga-DOTATOC PET/computed tomography (PET/CT) in patients with known gastroenteropancreatic neuroendocrine tumors (NETs). MATERIALS AND METHODS: Eight patients (4 women and 4 men; mean [SD] age, 54 [17] years; median, 55 years; range 25-74 years) with histopathologically confirmed NET and scheduled Ga-DOTATOC PET/CT were prospectively enrolled for an additional integrated PET/MRI scan. Positron emission tomography/computed tomography was performed using a triple-phase contrast-enhanced full-dose protocol. Positron emission tomography/magnetic resonance imaging encompassed a diagnostic, contrast-enhanced whole-body MRI protocol. Two readers separately analyzed the PET/CT and PET/MRI data sets including their subscans in random order regarding lesion localization, count, and characterization on a 4-point ordinal scale (0, not visible; 1, benign; 2, indeterminate; and 3, malignant). In addition, each lesion was rated in consensus on a binary scale (allowing for benign/malignant only). Clinical imaging, existing prior examinations, and histopathology (if available) served as the standard of reference. In PET-positive lesions, the standardized uptake value (SUVmax) was measured in consensus. A descriptive, case-oriented data analysis was performed, including determination of frequencies and percentages in detection of malignant, benign, and indeterminate lesions in connection to their  localization. In addition, percentages in detection by a singular modality (such  as PET, CT, or MRI) were calculated. Interobserver variability was calculated (Cohen’s kappa). The SUVs in the lesions in PET/CT and PET/MRI were measured, and the correlation coefficient (Pearson, 2-tailed) was calculated. RESULTS: According to the reference standard, 5 of the 8 patients had malignant NET lesions at the time of the examination. A total of 4 patients were correctly identified by PET/CT, with the PET and CT component correctly identifying 3 patients each. All 5 patients positive for NET disease were correctly identified  by PET/MRI, with the MRI subscan identifying all 5 patients and the PET subscan identifying 3 patients. All lesions considered as malignant in PET/CT were equally depicted in and considered using PET/MRI. One liver lesion rated as “indetermined” in PET/CT was identified as metastasis in PET/MRI because of a diffusion restriction in diffusion-weighted imaging. Of the 4 lung lesions characterized in PET/CT, only 1 was depicted in PET/MRI. Of the 3 lymph nodes depicted in PET/CT, only 1 was characterized in PET/MRI. Interobserver reliability was equally very good in PET/CT (kappa = 0.916) and PET/MRI (kappa =  1.0). The SUVmax measured in PET/CT and in PET/MRI showed a strong correlation (Pearson correlation coefficient, 0.996). CONCLUSIONS: This pilot study demonstrates the potential of Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic NET, with special advantages in the characterization of abdominal lesions yet certain weaknesses inherent to MRI, such as lung metastases and hypersclerotic bone lesions.

 

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[65]

TÍTULO / TITLE:  - Aberrant Expression of Mucin Core Proteins and O-Linked Glycans Associated with Progression of Pancreatic Cancer.

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

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Apr 3.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2662

AUTORES / AUTHORS:  - Remmers N; Anderson JM; Linde EM; Dimaio DJ; Lazenby AJ; Wandall HH; Mandel U; Clausen H; Yu F; Hollingsworth MA

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Biochemistry and Molecular Biology and Pathology and Microbiology; Eppley Institute for Research in Cancer and Allied Diseases; Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska; Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine; and School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

RESUMEN / SUMMARY:  - PURPOSE: Mucin expression is a common feature of most adenocarcinomas and features prominently in current attempts to improve diagnosis and therapy for pancreatic cancer and other adenocarcinomas. We investigated the expression of a  number of mucin core proteins and associated O-linked glycans expressed in pancreatic adenocarcinoma-sialyl Tn (STn), Tn, T antigen, sialyl Lewis A (CA19-9), sialyl Lewis C (SLeC), Lewis X (LeX), and sialyl LeX (SLeX)-during the  progression of pancreatic cancer from early stages to metastatic disease.EXPERIMENTAL DESIGN: Immunohistochemical analyses of mucin and associated glycan expression on primary tumor and liver metastatic tumor samples were conducted with matched sets of tissues from 40 autopsy patients diagnosed with pancreatic adenocarcinoma, 14 surgically resected tissue samples, and 8 normal pancreata.RESULTS: There were significant changes in mucin expression patterns throughout disease progression. MUC1 and MUC4 were differentially glycosylated as the disease progressed from early pancreatic intraepithelial neoplasias to metastatic disease. De novo expression of several mucins correlated with increased metastasis indicating a potentially more invasive phenotype, and we show the expression of MUC6 in acinar cells undergoing acinar to ductal metaplasia. A “cancer field-effect” that included changes in mucin protein expression and glycosylation in the adjacent normal pancreas was also seen.CONCLUSIONS: There are significant alterations in mucin expression and posttranslational processing during progression of pancreatic cancer from early lesions to metastasis. The results are presented in the context of how mucins influence the biology of tumor cells and their microenvironment during progression of pancreatic cancer. Clin Cancer Res; 19(8); 1-13. ©2013 AACR.

 

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[66]

TÍTULO / TITLE:  - Inflammatory Plasma Markers and Pancreatic Cancer Risk: a Prospective Study of 5  U.S. Cohorts.

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

REVISTA / JOURNAL:  - Cancer Epidemiol Biomarkers Prev. 2013 Mar 5.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1055-9965.EPI-12-1458

AUTORES / AUTHORS:  - Bao Y; Giovannucci E; Kraft P; Qian ZR; Wu C; Ogino S; Gaziano JM; Stampfer MJ; Ma J; Buring JE; Sesso H; Lee IM; Rifai N; Pollak MN; Jiao L; Lessin LS; Cochrane BB; Manson JE; Fuchs CS; Wolpin BM

INSTITUCIÓN / INSTITUTION:  - 1Department of Medicine, Brigham and Women’s Hospital.

RESUMEN / SUMMARY:  - BACKGROUND: Chronic inflammation may play a role in the development of pancreatic cancer. However, few prospective studies have examined the association between plasma inflammatory markers and pancreatic cancer risk. METHODS: In a prospective, nested case-control study of 470 cases and 1094 controls from Health Professionals Follow-up Study, Nurses’ Health Study, Physicians’ Health Study, Women’s Health Initiative, and Women’s Health Study, we investigated the association of prediagnostic circulating C-reactive protein (CRP), interleukin-6  (IL-6), and tumor necrosis factor-alpha-receptor II (TNF-alphaR2) with subsequent pancreatic cancer risk. The median follow-up time of cases was 7.2 years (range 1-26 years). RESULTS: No association was observed between plasma CRP, IL6, and TNF-alphaR2 and risk of pancreatic cancer. Comparing extreme quintiles, the multivariate ORs were 1.10 (95% CI, 0.74-1.63; Ptrend= 0.81) for CRP, 1.19 (95% CI, 0.81-1.76; Ptrend = 0.08) for IL6, and 0.88 (95% CI, 0.58-1.33; Ptrend = 0.57) for TNF-alphaR2. CONCLUSIONS: Pre-diagnostic levels of circulating CRP, IL6, and TNF-alphaR2 were not associated with risk of pancreatic cancer. Impact:  Systemic inflammation as measured by circulating inflammatory factors is unlikely to play a major role in the development of pancreatic cancer.

 

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[67]

TÍTULO / TITLE:  - Role of SUVmax obtained by 18F-FDG PET/CT in patients with a solitary pancreatic  lesion: predicting malignant potential and proliferation.

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

REVISTA / JOURNAL:  - Nucl Med Commun. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MNM.0b013e328360668a

AUTORES / AUTHORS:  - Hu SL; Yang ZY; Zhou ZR; Yu XJ; Ping B; Zhang YJ

INSTITUCIÓN / INSTITUTION:  - Departments of aNuclear Medicine bDiagnostic Radiology cPancreas & Hepatobililary Surgery dPathology, Fudan University Shanghai Cancer Center eDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

RESUMEN / SUMMARY:  - OBJECTIVES: Maximum standardized uptake value (SUVmax) is a marker of tumor glucose metabolism detected by [F]-fluorodeoxyglucose (F-FDG) PET/computed tomography (PET/CT) and reflects tumor aggressiveness. The aim of the study was to evaluate the value of SUVmax in differentiating benign from malignant solitary pancreatic lesions and explore the correlation between SUVmax and tumor proliferative activity. MATERIALS AND METHODS: F-FDG PET/CT scans were performed  in 80 patients with solitary pancreatic lesions who were scheduled for resective  surgery. The relationships between SUVmax and postoperative pathologic diagnosis, histologic grade, and Ki-67 proliferation index (PI) were analyzed. RESULTS: Of these 80 patients, 54 had malignant lesions. The SUVmax of malignant tumors (6.3+/-2.4) was significantly greater than that of benign lesions (2.9+/-2.0) (P<0.001). Receiver-operating characteristic curve analysis showed that the SUVmax cutoff value of 3.5 had a high sensitivity (92.6%) and specificity (76.9%) for the diagnosis of malignancies. Among pancreatic cancers with low (Ki-67<5%),  moderate (5%</=Ki-67<50%), and high (Ki-67>/=50%) PI, SUVmax increased significantly from 4.2+/-1.2, through 6.0+/-1.7, to 8.6+/-2.5 (P<0.001). The SUVmax had a positive correlation with Ki-67 PI (P<0.001, r=0.60). CONCLUSION: The SUVmax of F-FDG PET/CT can be used in the differential diagnosis of solitary  pancreatic lesions and can also aid in the prediction of proliferative activity of pancreatic cancer.

 

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[68]

TÍTULO / TITLE:  - Initial impact of a systematic multidisciplinary approach on the management of patients with gastroenteropancreatic neuroendocrine tumor.

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

REVISTA / JOURNAL:  - Endocrine. 2013 Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12020-013-9910-5

AUTORES / AUTHORS:  - Tamagno G; Sheahan K; Skehan SJ; Geoghegan JG; Fennelly D; Collins CD; Maguire D; Traynor O; Brophy DP; Cantwell C; Swan N; McGowan L; O’Toole D; O’Shea D

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology & Diabetes Mellitus, St Vincent’s University Hospital-University College Dublin, 4 Elm Park, Dublin 4, Ireland, gianlucatamagno@tiscali.it.

RESUMEN / SUMMARY:  - According to the international guidelines, a multidisciplinary approach is currently advised for the optimal care of patients with a gastroenteropancreatic  neuroendocrine tumor (GEP NET). In our institution (tertiary care center), a systematic multidisciplinary approach was established in May 2007. In this study, we have aimed to assess the initial impact of establishing a systematic multidisciplinary approach to the management of GEP NET patients. We have collected and compared the biochemical, imaging, and pathological data and the therapeutic strategies in GEP NET patients diagnosed, treated, or followed-up from January 1993 to April 2007 versus GEP NET patients attending our institution after the multidisciplinary approach starting, from May 2007 to October 2008. Data of 91 patients before and 42 patients after the establishment of the multidisciplinary approach (total: 133 consecutive GEP NET patients) have been finally collected and analyzed. Before the establishment of the multidisciplinary approach, a lack of consistency in the biochemical, imaging, and pathological findings before treatment initiation as well as during follow-up of GEP NET patients was identified. These inconsistencies have been reduced by the systematic multidisciplinary approach. In addition, the therapeutic management of GEP NET patients has been altered by the multidisciplinary approach and became more consistent with recommended guidelines. We think that a systematic multidisciplinary approach significantly impacts on GEP NET patient care and should be established in all centers dealing with these tumors.

 

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[69]

TÍTULO / TITLE:  - Targeting the NF-kappaB and mTOR pathways with a quinoxaline urea analog that inhibits IKKbeta for pancreas cancer therapy.

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

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2909

AUTORES / AUTHORS:  - Radharkrishnan P; Bryant VC; Blowers EC; Rajule R; Gautham N; Anwar MM; Mohr AM; Grandgenett PM; Bunt S; Arnst JL; Lele SM; Alnouti Y; Hollingsworth MT; Natarajan A

INSTITUCIÓN / INSTITUTION:  - Eppley Cancer Center, University of Nebraska Medical Center.

RESUMEN / SUMMARY:  - PURPOSE: The presence of TNFalpha in ~ 50% of surgically resected tumors suggests that the canonical NF-kappaB and the mTOR pathways are activated. IkappaB kinase  beta (IKKbeta) acts as the signaling node that regulates transcription via the p-IkappaBalpha / NF-kappaB axis and regulates translation via the mTOR / p-S6K /  p-eIF4EBP axis. A kinome screen identified a quinoxaline urea analog 13-197 as an IKKbeta inhibitor. We hypothesized that targeting the NF-kappaB and mTOR pathways with 13-197 will be effective in malignancies driven by these pathways. EXPERIMENTAL DESIGN: Retrospective clinical and preclinical studies in pancreas cancers have implicated NF-kappaB. We examined the effects of 13-197, on the downstream targets of the NF-kappaB and mTOR pathways in pancreatic cancer cells, pharmacokinetics, toxicity and tumor growth and metastases in vivo. RESULTS: 13-197 inhibited the kinase activity of IKKbeta in vitro and TNFalpha mediated NF-kappaB transcription in cells with low-muM potency. 13-197 inhibited the phosphorylation of IkappaBalpha, S6K and eIF4EBP, induced G1 arrest and down regulated the expression of antiapoptotic proteins in pancreatic cancer cells. Prolonged administration of 13-197 did not induce granulocytosis and protected mice from LPS-induced death. Results also show that 13-197 is orally available with extensive distribution to peripheral tissues and inhibited tumor growth and  metastasis in an orthotopic pancreatic cancer model without any detectable toxicity. CONCLUSIONS: These results suggest that 13-197 targets IKKbeta and thereby inhibits mTOR and NF-kappaB pathways. Oral availability along with in vivo efficacy without obvious toxicities makes this quinoxaline urea chemotype, a viable cancer therapeutic.

 

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[70]

TÍTULO / TITLE:  - New-onset diabetic patients need pancreatic cancer screening.

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

REVISTA / JOURNAL:  - J Clin Gastroenterol. 2013 Apr;47(4):372. doi: 10.1097/MCG.0b013e318275895b.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MCG.0b013e318275895b

AUTORES / AUTHORS:  - Lai SW; Liao KF

INSTITUCIÓN / INSTITUTION:  - *School of Medicine, China Medical University daggerDepartment of Family Medicine, China Medical University Hospital double daggerDepartment of Internal Medicine Taichung Tzu Chi General Hospital parallelDepartment of Health Care Administration, Central Taiwan University of Science and Technology, Taichung section signGraduate Institute of Integrated Medicine, China Medical University,  Taichung, Taiwan.

 

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[71]

TÍTULO / TITLE:  - Safety evaluation of high-intensity focused ultrasound in patients with pancreatic cancer.

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

REVISTA / JOURNAL:  - Onkologie. 2013;36(3):88-92. doi: 10.1159/000348530. Epub 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000348530

AUTORES / AUTHORS:  - Wang K; Zhu H; Meng Z; Chen Z; Lin J; Shen Y; Gao H

INSTITUCIÓN / INSTITUTION:  - Department of Integrated Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

RESUMEN / SUMMARY:  - Introduction: This study was performed to analyze the safety of high-intensity focused ultrasound (HIFU) for treating pancreatic cancer. Methods: 224 cases with advanced pancreatic cancer were enrolled into this study. Real-time sonographic images were taken, and vital signs, liver and kidney function, skin burns, local  reactions, and systemic effects were monitored and recorded before, during, and after HIFU. Computed tomography or magnetic resonance imaging (MRI) was also performed before and after HIFU. Results: Serum amylase level increased in 16 cases (7.1%) 1 day after HIFU treatment, and 9 of these cases also had abnormal urinary amylase levels. Gastrointestinal (GI) dysfunction such as abdominal distension and anorexia with slight nausea was observed in 10 cases (4.5%) after  HIFU treatment. 1 case with pancreatic head cancer developed obstructive jaundice 2 weeks after HIFU treatment. Vertebral injury, identified by MRI, occurred in 2  cases, although no symptoms were seen. No severe complications such as skin burns, lesion bleeding, GI tract bleeding or GI perforation were observed in any  of the cases. Conclusion: For specific patients, HIFU treatment is a safe, non-invasive treatment for pancreatic cancer but requires careful preoperative preparation and exact operative performance.

 

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[72]

TÍTULO / TITLE:  - Decision making for pancreatic resection in patients with intraductal papillary mucinous neoplasms.

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

REVISTA / JOURNAL:  - World J Gastroenterol. 2013 Mar 7;19(9):1451-7. doi: 10.3748/wjg.v19.i9.1451.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i9.1451

AUTORES / AUTHORS:  - Xu B; Ding WX; Jin DY; Wang DS; Lou WH

INSTITUCIÓN / INSTITUTION:  - Bin Xu, Wei-Xing Ding, Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China.

RESUMEN / SUMMARY:  - AIM: To identify a practical approach for preoperative decision-making in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: Between March 1999 and November 2006, the clinical characteristics, pathological data and computed tomography/magnetic resonance imaging (CT/MRI) of  54 IPMNs cases were retrieved and analyzed. The relationships between the above data and decision-making for pancreatic resection were analyzed using SPSS 13.0 software. Univariate analysis of risk factors for malignant or invasive IPMNs was performed with regard to the following variables: carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and the characteristics from CT/MRI images. Receiver operating characteristic (ROC) curve analysis for pancreatic resection was performed using significant factors from the univariate analysis. RESULTS: CT/MRI images, including main and mixed duct IPMNs, tumor size > 30 mm or a solid component appearance in the lesion, and preoperative serum CA19-9 > 37 U/mL had good predictive value for determining pancreatic resection (P < 0.05), but with limitations. Combining the above factors (CT/MRI images and CA19-9) improved the  accuracy and sensitivity for determining pancreatic resection in IPMNs. Using ROC analysis, the area under the curve reached 0.893 (P < 0.01, 95%CI: 0.763-1.023),  with a sensitivity, specificity, positive predictive value and negative predictive value of 95.2%, 83.3%, 95.2% and 83.3%, respectively. CONCLUSION: Combining preoperative CT/MRI images and CA19-9 level may provide useful information for surgical decision-making in IPMNs.

 

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[73]

TÍTULO / TITLE:  - Mechanistic insights into self-reinforcing processes driving abnormal histogenesis during the development of pancreatic cancer.

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

REVISTA / JOURNAL:  - Am J Pathol. 2013 Apr;182(4):1078-86. doi: 10.1016/j.ajpath.2012.12.004. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2012.12.004

AUTORES / AUTHORS:  - Iovanna JL; Marks DL; Fernandez-Zapico ME; Urrutia R

INSTITUCIÓN / INSTITUTION:  - Cancer Research Center of Marseille, Inserm U1068, CNRS, UMR7258, Institute Paoli-Calmettes, Aix-Marseille University, Marseille, France.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma, one of the most feared lethal and painful diseases, is increasing in incidence. The poor prognosis of pancreatic ductal adenocarcinoma-affected patients primarily is owing to our inability to develop effective therapies. Mechanistic studies of genetic, epigenetic, and cell-to-cell signaling events are providing clues to molecular pathways that can be targeted in an attempt to cure this disease. The current review article seeks to draw inferences from available mechanistic knowledge to build a theoretical framework  that can facilitate these approaches. This conceptual model considers pancreatic  cancer as a tissue disease rather than an isolated epithelial cell problem, which develops and progresses in large part as a result of three positive feedback loops: i) genetic and epigenetic changes in epithelial cells modulate their interaction with mesenchymal cells to generate a dynamically changing process of  abnormal histogenesis, which drives more changes; ii) the faulty tissue architecture of neoplastic lesions results in unsynchronized secretion of signaling molecules by cells, which generates an environment that is poor in oxygen and nutrients; and iii) the increased metabolic needs of rapidly dividing  cells serve as an evolutionary pressure for them to adapt to this adverse microenvironment, leading to the emergence of resistant clones. We discuss how these concepts can guide mechanistic studies, as well as aid in the design of novel experimental therapeutics.

 

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[74]

TÍTULO / TITLE:  - Protein kinase Calpha inhibitor protects against downregulation of claudin-1 during epithelial-mesenchymal transition of pancreatic cancer.

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

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt057

AUTORES / AUTHORS:  - Kyuno D; Kojima T; Yamaguchi H; Ito T; Kimura Y; Imamura M; Takasawa A; Murata M; Tanaka S; Hirata K; Sawada N

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and.

RESUMEN / SUMMARY:  - Protein kinase Calpha (PKCalpha) is highly expressed in pancreatic cancer. However, the effects of PKCalpha on Snail and claudin-1, which play crucial roles in epithelial cell polarity during epithelial-mesenchymal transition (EMT), remain unclear. In this study, we investigated the mechanisms of regulation of Snail and claudin-1 via a PKCalpha signal pathway during EMT in pancreatic cancer cells and in normal human pancreatic duct epithelial cells (HPDEs). By immunostaining, overexpression of PKCalpha and downregulation of claudin-1 were observed in poorly differentiated human pancreatic cancer tissues and the pancreatic cancer cell line PANC-1. Treatment with the PKCalpha inhibitor Go6976  transcriptionally decreased Snail and increased claudin-1 in PANC-1 cells. The PKCalpha inhibitor prevented upregulation of Snail and downregulation of claudin-1 during EMT induced by transforming growth factor-beta1 (TGF-beta1) treatment and under hypoxia in PANC-1 cells. The effects of the PKCalpha inhibitor were in part regulated via an extracellular signal-regulated kinase (ERK) signaling pathway. The PKCalpha inhibitor also prevented downregulation of  the barrier function and fence function during EMT in well-differentiated pancreatic cancer cell line HPAC. In normal HPDEs, the PKCalpha inhibitor transcriptionally induced not only claudin-1 but also claudin-4, -7 and occludin  without a change of Snail. Treatment with the PKCalpha inhibitor in normal HPDEs  prevented downregulation of claudin-1 and occludin by TGF-beta1 treatment and enhanced upregulation of claudin-1, -4, -7 and occludin under hypoxia. These findings suggest that PKCalpha regulates claudin-1 via Snail- and mitogen-activated protein kinase/ERK-dependent pathways during EMT in pancreatic  cancer. Thus, PKCalpha inhibitors may be potential therapeutic agents against the malignancy of human pancreatic cancer cells.

 

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[75]

TÍTULO / TITLE:  - Characteristics of Notch2 pancreatic cancer stem-like cells and the relationship  with centroacinar cells.

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

REVISTA / JOURNAL:  - Cell Biol Int. 2013 Mar 28. doi: 10.1002/cbin.10102.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cbin.10102

AUTORES / AUTHORS:  - Ni QX

INSTITUCIÓN / INSTITUTION:  - 270 Dongan Road, Shanghai, China, 200032.

RESUMEN / SUMMARY:  - Notch2, a surface marker in cell lines, is used to isolate, identify and localize pancreatic cancer stem-like cells and is a target for therapy of these cells. Sphere formation was induced in Panc-1 and Bxpc-3 pancreatic cancer cell lines, and Notch2+ cells were separated from Bxpc-3 and Panc-1 cell lines by magnetic activated cell sorting (MACS). Expression of stem cell-related markers, OCT4, Nanog and PDX1, were measured by immunofluoresent (IF) staining. Expression of Notch2 was also determined immunohistochemically in pancreatic tissues. Notch2+ cells were transplanted in subcutaneous of mice. AQP1 and AQP5 were also measured by IF in Bxpc-3 cells. The Notch signal pathway inhibitor, Compound E (CE), was used to treat Notch2+ Bxpc-3 cells, and their vitalities were subsequently measured by the CCK-8 method. Positive expression of OCT4, Nanog and PDX1 was observed in Notch2+ cells. Notch2+ cells at centroacinar cell (CAC) and terminal  ductal locations expressed AQP1 and AQP5. They were strongly tumorigenic in mice, and CE inhibited proliferation of Notch2+ Bxpc-3 cells to some degree. OCT4 and Nanog can be used as markers of self-renewal in pancreatic cancer stem cells. Notch2+ cells in human pancreatic cancer Bxpc-3 and Panc-1 cell lines had the properties of cancer stem cells. The results suggest that Notch2+ pancreatic cancer stem-like cells had a close relationship with CAC.

 

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[76]

TÍTULO / TITLE:  - The Cost-Effectiveness of Neoadjuvant Chemoradiation is Superior to a Surgery-First Approach in the Treatment of Pancreatic Head Adenocarcinoma.

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

REVISTA / JOURNAL:  - Ann Surg Oncol. 2013 Feb 10.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2882-0

AUTORES / AUTHORS:  - Abbott DE; Tzeng CW; Merkow RP; Cantor SB; Chang GJ; Katz MH; Bentrem DJ; Bilimoria KY; Crane CH; Varadhachary GR; Abbruzzese JL; Wolff RA; Lee JE; Evans DB; Fleming JB

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA.

RESUMEN / SUMMARY:  - BACKGROUND: In treating pancreatic cancer, there is no clearly defined optimal sequence of chemotherapy, radiation therapy and surgery. Therefore, cost-effectiveness should be considered. The objective of this study was to compare cost and outcomes between a surgery-first approach versus neoadjuvant chemoradiation followed by surgery for resectable pancreatic head cancer. METHODS: A decision analytic model was constructed to compare the 2 approaches. Data from the National Cancer Database, National Surgical Quality Improvement Program, and literature populated the surgery-first arm. Data from our prospectively maintained institutional pancreatic cancer database populated the neoadjuvant arm. Costs were estimated by Medicare payment (2011 U.S. dollars). Survival was reported in quality-adjusted life-months (QALMs). RESULTS: The neoadjuvant chemoradiation arm consisted of 164 patients who completed preoperative therapy. Of these, 36 (22 %) did not proceed to surgery; 12 (7 %) underwent laparotomy but had unresectable disease; and 116 (71 %) underwent definitive resection. The surgery-first approach cost $46,830 and yielded survival of 8.7 QALMs; the neoadjuvant chemoradiation approach cost $36,583 and yielded survival of 18.8 QALMs. In the neoadjuvant arm, costs and survival times  for patients not undergoing surgery, those with unresectable disease at laparotomy, and those completing surgery were $12,401 and 7.7 QALMs, $20,380 and  7.1 QALMs, and $45,673 and 23.4 QALMs, respectively. CONCLUSIONS: Neoadjuvant chemoradiation for pancreatic cancer identifies patients with early metastases or poor performance status, who can be spared an ineffective or prohibitively morbid operation, and is associated with improved survival at significantly lower cost than a surgery-first approach. Neoadjuvant chemoradiation followed by surgery is  a strategy that provides more cost-effective care than a surgery-first approach.

 

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[77]

TÍTULO / TITLE:  - Do patient- and tumor-related factors predict the peritoneal spread of pancreatic adenocarcinoma?

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

REVISTA / JOURNAL:  - Surg Today. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00595-013-0546-0

AUTORES / AUTHORS:  - Konigsrainer I; Zieker D; Symons S; Horlacher K; Konigsrainer A; Beckert S

INSTITUCIÓN / INSTITUTION:  - Department of General, Visceral and Transplant Surgery, University of Tubingen Comprehensive Cancer Center, Hoppe-Seyler-Strasse 3, 72076, Tubingen, Germany, ingmar.koenigsrainer@med.uni-tuebingen.de.

RESUMEN / SUMMARY:  - PURPOSE: In pancreatic cancer, the presence of peritoneal carcinomatosis (PC) precludes the possibility of a surgical cure, irrespective of the resectability of the primary tumor. However, peritoneal spread cannot be reliably detected radiographically during preoperative tumor staging. METHODS: The pancreatic adenocarcinoma database of the Tubingen Comprehensive Cancer Center included 29 patients in whom PC was incidentally detected during the surgery. These patients  were retrospectively compared for patient- and tumor-related factors with 29 randomly selected patients without PC who underwent curative resection. RESULTS:  Clinical jaundice and diarrhea were more frequently present in patients without PC. The CA 19-9 levels were significantly higher in patients with PC compared to  those in patients without PC. No other differences were observed in the patient-  or tumor-related factors between the two groups. CONCLUSION: In pancreatic cancer patients, markedly elevated CA 19-9 levels may serve as surrogate marker for peritoneal dissemination, irrespective of the local resectability of the tumor. In such patients, laparoscopy should be considered as an additional staging tool  to rule out peritoneal carcinomatosis.

 

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[78]

TÍTULO / TITLE:  - Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area.

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

REVISTA / JOURNAL:  - Nutr Cancer. 2013;65(1):157-64. doi: 10.1080/01635581.2012.725502.

            ●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2012.725502

AUTORES / AUTHORS:  - Chan JM; Gong Z; Holly EA; Bracci PM

INSTITUCIÓN / INSTITUTION:  - Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94158-9001, USA. june.chan@ucsf.edu

RESUMEN / SUMMARY:  - Pancreatic cancer is highly lethal, and identifying modifiable risk factors could have substantial public health impact. In this population-based case-control study (532 cases, 1701 controls), we used principal component analysis and multivariable unconditional logistic regression models to examine whether a particular dietary pattern was associated with risk of pancreatic cancer, adjusting for other known risk factors. A prudent dietary pattern, characterized  by greater intake of vegetables, fruit, fish, poultry, whole grains, and low-fat  dairy, was associated with an approximate 50% reduction in pancreatic cancer risk among men [odds ratio (OR) = 0.51, 95% confidence intervals (CI) = 0.31-0.84, P trend = 0.001] and women (OR = 0.51, 95% CI = 0.29-0.90, P trend = 0.04). A Western dietary pattern, characterized by higher intake of red and processed meats, potato chips, sugary beverages, sweets, high fat dairy, eggs, and refined  grains, was associated with a 2.4-fold increased risk of pancreatic cancer among  men (95% CI = 1.3-4.2, P trend = 0.008) but was not associated with risk among women. Among men, those in the upper quintiles of the Western diet and lower quintiles of the prudent diet had a threefold increased risk. Consistent with what has been recommended for several other chronic diseases, consuming a diet rich in plant-based foods, whole grains, and white meat, might reduce risk of pancreatic cancer.

 

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[79]

TÍTULO / TITLE:  - Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody.

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

REVISTA / JOURNAL:  - Int J Oncol. 2013 Apr;42(4):1229-38. doi: 10.3892/ijo.2013.1821. Epub 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1821

AUTORES / AUTHORS:  - Wu Y; Antony S; Hewitt SM; Jiang G; Yang SX; Meitzler JL; Juhasz A; Lu J; Liu H; Doroshow JH; Roy K

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

RESUMEN / SUMMARY:  - Dual oxidase 2 (Duox2), one of the seven members of the NADPH oxidase gene family, plays a critical role in generating H2O2 for thyroid hormone biosynthesis and as an integral part of the host defense system of the respiratory epithelium  and the gastrointestinal tract. Recent evidence suggests that the regulation of Duox2 expression is under the control of pro-inflammatory cytokines and that Duox2-induced reactive oxygen species (ROS) contribute to the inflammation-related tissue injury that occurs in two pre-malignant, inflammatory conditions: chronic pancreatitis and inflammatory bowel disease. Because no reliable Duox antibodies are commercially available, we report the development of a murine monoclonal antibody (MAb) to Duox2 (clone Duox S-12) and its use for the characterization of Duox2 expression in human tumors, tumor cell lines and normal tissues. Duox S-12 specifically detected both endogenously- and ectopically-expressed Duox2 protein by immunoblotting, immunofluorescence microscopy and immunohistochemistry (where both membranous and cytoplasmic staining were present). Duox2 expression detected by Duox S-12 was functionally coupled to the generation of H2O2 in pancreatic cancer cells that expressed Duox2 and its cognate maturation factor DuoxA2. Although Duox S-12 recognizes ectopically expressed Duox1 protein because of the extensive amino acid homology  between Duox1 and Duox2, the lack of substantial Duox1 mRNA expression in human tumors (except thyroid cancer) allowed us to evaluate Duox2 expression across a wide range of normal and malignant tissues by immuno-histochemistry. Duox2 was expressed at elevated levels in many human cancers, most notably tumors of the prostate, lung, colon and breast while brain tumors and lymphomas demonstrated the lowest frequency of expression. The Duox-specific monoclonal antibody described here provides a promising tool for the further examination of the role  of Duox-dependent reactive oxygen production in inflammation-related carcinogenesis, where alterations in oxidant tone play a critical role in cell growth and proliferation.

 

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[80]

TÍTULO / TITLE:  - Heparin-binding epidermal growth factor-like growth factor eliminates constraints on activated Kras to promote rapid onset of pancreatic neoplasia.

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

REVISTA / JOURNAL:  - Oncogene. 2013 Feb 4. doi: 10.1038/onc.2013.3.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.3

AUTORES / AUTHORS:  - Ray KC; Moss ME; Franklin JL; Weaver CJ; Higginbotham J; Song Y; Revetta FL; Blaine SA; Bridges LR; Guess KE; Coffey RJ; Crawford HC; Washington MK; Means AL

INSTITUCIÓN / INSTITUTION:  - Division of Surgical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.

RESUMEN / SUMMARY:  - Pancreatic cancer remains as one of the most deadly cancers with few treatment options at late stages and little information about how it develops through earlier stages. Activating mutation of the Kras gene has been implicated in, but  is not sufficient for, tumorigenesis. In mouse models of pancreatic cancer, loss  of tumor suppressor genes in conjunction with Kras mutation leads to gradual stochastic acquisition of neoplastic precursors and carcinomas, whereas many cells remain phenotypically unaltered in younger mice. Here, we demonstrate that  two oncogenic events, mutation of Kras and production of the growth factor heparin-binding epidermal growth factor-like growth factor (HB-EGF), are sufficient for rapid and complete neoplastic transformation of the exocrine pancreas. We found that macrophages are the major source of HB-EGF production in  pancreatic cancer tissue samples, and that macrophages are present in high density and in close association with human pancreatic cancer lesions. In a mouse model, high macrophage density was observed at the earliest stages of neoplastic  transformation. The consequence of elevated HB-EGF signaling was investigated without the confounding effects of other macrophage-produced factors via transgenic overexpression of the active form of HB-EGF. In this model, HB-EGF was sufficient to promote Kras-initiated tumorigenesis, inducing rapid and complete neoplastic transformation of the entire exocrine pancreas shortly after birth. HB-EGF overexpression and Kras(G12D) together, but neither alone, increased proliferation with increased cyclinD1 and decreased Cdkn2a/2d (p16/p19(Ink4A/Arf)). These findings establish the importance of oncogenic synergy in cancer initiation and promotion, and establish a molecular link between inflammation and the earliest stages of tumor induction.Oncogene advance  online publication, 4 February 2013; doi:10.1038/onc.2013.3.

 

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[81]

TÍTULO / TITLE:  - Frequency and Intensity of Postoperative Surveillance After Curative Treatment of Pancreatic Cancer: A Cost-Effectiveness Analysis.

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

REVISTA / JOURNAL:  - Ann Surg Oncol. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2889-6

AUTORES / AUTHORS:  - Tzeng CW; Abbott DE; Cantor SB; Fleming JB; Lee JE; Pisters PW; Varadhachary GR; Abbruzzese JL; Wolff RA; Ahmad SA; Katz MH

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, cdtzeng@mdanderson.org.

RESUMEN / SUMMARY:  - BACKGROUND: Few data exist to guide oncologic surveillance following curative treatment of pancreatic cancer. We sought to identify a rational, cost-effective  postoperative surveillance strategy. METHODS: We constructed a Markov model to compare the cost-effectiveness of 5 postoperative surveillance strategies. No scheduled surveillance served as the baseline strategy. Clinical evaluation and carbohydrate antigen (CA) 19-9 testing without/with routine computed tomography and chest X-ray at either 6- or 3-month intervals served as the 4 comparison strategies of increasing intensity. We populated the model with symptom, recurrence, treatment, and survival data from patients who had received intensive surveillance after multimodality treatment at our institution between 1998 and 2008. Costs were based on Medicare payments (2011 US dollars). RESULTS: The baseline strategy of no scheduled surveillance was associated with a postoperative overall survival (OS) of 24.6 months and a cost of $3837/patient. Clinical evaluation and CA 19-9 assay every 6 months until recurrence was associated with a 32.8-month OS and a cost of $7496/patient, with an incremental  cost-effectiveness ratio (ICER) of $5364/life-year (LY). Additional routine imaging every 6 months incrementally increased total cost by $3465 without increasing OS. ICERs associated with clinic visits every 3 months without/with routine imaging were $127,680 and $294,696/LY, respectively. Sensitivity analyses changed the strategies’ absolute costs but not the relative ranks of their ICERs. CONCLUSIONS: Increasing the frequency and intensity of postoperative surveillance of patients after curative therapy for pancreatic cancer beyond clinical evaluation and CA 19-9 testing every 6 months increases cost but confers no clinically significant survival benefit.

 

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[82]

TÍTULO / TITLE:  - Exploiting inflammation for therapeutic gain in pancreatic cancer.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Mar 19;108(5):997-1003. doi: 10.1038/bjc.2013.24. Epub 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.24

AUTORES / AUTHORS:  - Steele CW; Jamieson NB; Evans TR; McKay CJ; Sansom OJ; Morton JP; Carter CR

INSTITUCIÓN / INSTITUTION:  - 1] The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK [2] Department  of Surgery, West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G4 0SF, UK.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC.

 

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[83]

TÍTULO / TITLE:  - Added value of diffusion-weighted imaging to MR cholangiopancreatography with unenhanced MR imaging for predicting malignancy or invasiveness of intraductal papillary mucinous neoplasm of the pancreas.

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

REVISTA / JOURNAL:  - J Magn Reson Imaging. 2013 Feb 6. doi: 10.1002/jmri.24022.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jmri.24022

AUTORES / AUTHORS:  - Kang KM; Lee JM; Shin CI; Baek JH; Kim SH; Yoon JH; Han JK; Choi BI

INSTITUCIÓN / INSTITUTION:  - Department of Radiology and Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea.

RESUMEN / SUMMARY:  - PURPOSE: To investigate the added value of diffusion-weighted imaging (DWI) to magnetic resonance cholangiopancreatography (MRCP) with unenhanced MR imaging for predicting the malignancy or invasiveness of intraductal papillary mucinous neoplasms (IPMNs). MATERIALS AND METHODS: Following Institutional Review Board (IRB) approval, this retrospective study included 52 patients with surgically resected IPMNs and who underwent MRCP, unenhanced MRI, and DWI. Three blinded radiologists evaluated the two image sets, ie, MRCP with unenhanced MR images vs. the combined set with MRCP, unenhanced MR images, and DWI, and scored their confidence for malignancy or for invasiveness of IPMNs. The mean apparent diffusion coefficient (ADC) values of benign IPMNs and of intraductal mucinous carcinomas (IPMCs) were compared. The diagnostic accuracy was calculated using receiver operating characteristic (ROC) curve analysis. ESULTS: The mean ADC of malignant IPMNs (2.05 +/- 0.66 x 10(-3) mm(2) /sec) was significantly lower than  that of benign IPMNs (2.95 +/- 0.32 x 10(-3) mm(2) /sec, P < 0.0001). Invasive IPMCs (1.51 +/- 0.32 x 10(-3) mm(2) /sec) showed significantly lower ADC than that of noninvasive IPMCs (2.67 +/- 0.23 x 10(-3) mm(2) /sec, P = 0.0003). The area of diffusion restriction was more frequently seen in malignant IPMNs than in benign IPMNs (P < 0.00001). The addition of DWI to MRCP with unenhanced MRI did not show a significant improvement for predicting malignant IPMN (P> 0.05), but resulted in a tendency to improve the diagnostic accuracy for the prediction of invasive IPMN in two observers (P = 0.072, P = 0.085). CONCLUSION: The addition of DWI to MRCP with unenhanced MRI may improve the diagnosis of malignant IPMN and further increase the prediction of invasive IPMC. J. Magn. Reson. Imaging 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2013 Wiley Periodicals, Inc.

 

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[84]

TÍTULO / TITLE:  - LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.

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

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Apr 5;433(2):157-62. doi: 10.1016/j.bbrc.2013.02.038. Epub 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.02.038

AUTORES / AUTHORS:  - Amsterdam A; Raanan C; Schreiber L; Polin N; Givol D

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Cell Biology, The Weizmann Institute of Science, 234, Herzl Street, Rehovot 76100, Israel. Electronic address: abraham.amsterdam@weizmann.ac.il.

RESUMEN / SUMMARY:  - Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet’s beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer.

 

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[85]

TÍTULO / TITLE:  - A case of primary pancreatic Burkitt’s lymphoma diagnosed by EUS-guided FNA.

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

REVISTA / JOURNAL:  - Gastrointest Endosc. 2013 Mar 20. pii: S0016-5107(13)00096-5. doi: 10.1016/j.gie.2013.01.039.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gie.2013.01.039

AUTORES / AUTHORS:  - Nakaji S; Hirata N; Yoshimura S; Shiratori T; Kobayashi M; Ishii E; Matsue K

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Kameda Medical Center, Kamogawa City, Chiba, Japan.

 

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[86]

TÍTULO / TITLE:  - WNT7B mediates autocrine Wnt/beta-catenin signaling and anchorage-independent growth in pancreatic adenocarcinoma.

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

REVISTA / JOURNAL:  - Oncogene. 2013 Feb 18. doi: 10.1038/onc.2013.23.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.23

AUTORES / AUTHORS:  - Arensman MD; Kovochich AN; Kulikauskas RM; Lay AR; Yang PT; Li X; Donahue T; Major MB; Moon RT; Chien AJ; Dawson DW

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Laboratory Medicine, David Geffen School of Medicine  at UCLA, Los Angeles, CA, USA.

RESUMEN / SUMMARY:  - Developmental and cancer models show Wnt/beta-catenin-dependent signaling mediates diverse phenotypic outcomes in the pancreas that are dictated by context, duration and strength of activation. While generally assumed to be pro-tumorigenic, it is unclear to what extent dysregulation of Wnt/beta-catenin signaling impacts tumor progression in pancreatic adenocarcinoma (PDAC). In the present study, Wnt/beta-catenin activity was characterized across a spectrum of PDAC cell lines and primary tumors. Reporter and gene expression-based assays revealed wide heterogeneity in Wnt/beta-catenin transcriptional activity across PDAC cell lines and patient tumors, as well as variable responsiveness to exogenous Wnt ligand stimulation. An experimentally generated, pancreas-specific  gene expression signature of Wnt/beta-catenin transcriptional activation was used to stratify pathway activation across a cohort of resected, early-stage PDAC tumors (N=41). In this cohort, higher Wnt/beta-catenin activation was found to significantly correlate with lymphvascular invasion and worse disease-specific survival (median survival time 20.3 versus 43.9 months, log-rank P=0.03). Supporting the importance of Wnt ligand in mediating autocrine Wnt signaling, Wnt/beta-catenin activity was significantly inhibited in PDAC cell lines by WLS gene silencing and the small-molecule inhibitor IWP-2, both of which functionally block Wnt ligand processing and secretion. Transcriptional profiling revealed elevated expression of WNT7B occurred in PDAC cell lines with high levels of cell autonomous Wnt/beta-catenin activity. Gene-knockdown studies in AsPC-1 and HPAF-2 cell lines confirmed WNT7B-mediated cell autonomous Wnt/beta-catenin activation,  as well as an anchorage-independent growth phenotype. Our findings indicate WNT7B can serve as a primary determinant of differential Wnt/beta-catenin activation in PDAC. Disrupting the interaction between Wnt ligands and their receptors may be a particularly suitable approach for therapeutic modulation of Wnt/beta-catenin signaling in PDAC and other cancer contexts where Wnt activation is mediated by ligand expression rather than mutations in canonical pathway members.Oncogene advance online publication, 18 February 2013; doi:10.1038/onc.2013.23.

 

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[87]

TÍTULO / TITLE:  - Systems Biology Approaches to Pancreatic Cancer Detection, Prevention and Treatment.

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

REVISTA / JOURNAL:  - Curr Pharm Des. 2013 Mar 19.

AUTORES / AUTHORS:  - Alian OM; Philip PA; Sarkar FH; Azmi AS

INSTITUCIÓN / INSTITUTION:  - Department of Pathology Wayne State University School of Medicine 4100 John R HWCRC Room 732 Detroit MI, 48201 USA. azmia@karmanos.org.

RESUMEN / SUMMARY:  - Pancreatic cancer [PC] is a complex disease harboring multiple genetic alterations. It is now well known that deregulation in the expression and function of oncogenes and tumor suppressor genes contributes to the development and progression of PC. The last 40 years have not seen any major improvements in  the dismal overall cure rate for PC where drug resistance is an emerging and recurring obstacle for successful treatment of PC. Additionally, the lack of molecular biomarkers for patient selection limits drug availabilities for tailored therapy for patients diagnosed with PC. The very high failure rate of new drugs in Phase III clinical trials in PC calls for a more robust pre-clinical and clinical testing of new compounds. In order to rationally choose combinations of targeted agents that may improve therapeutic outcome by overcoming drug resistance, one needs to apply newer research tools such as systems and network biology. These newer tools are expected to assist in the design of effective drug combinations for the treatment of PC and are expected to become an important part in any future clinical trials. In this review we will provide background information on the current state of PC research, the reasons for drug failure and how to overcome these issues using systems sciences. We conclude this review with an example on how systems and network methodologies can help design efficacious drug combinations for this deadly and by far incurable disease.

 

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[88]

TÍTULO / TITLE:  - Multiple KRAS Mutations in Pancreatic Adenocarcinoma: Molecular Features of Neoplastic Clones Indicate the Selection of Divergent Populations of Tumor Cells.

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

REVISTA / JOURNAL:  - Int J Surg Pathol. 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1066896912475073

AUTORES / AUTHORS:  - Visani M; de Biase D; Baccarini P; Fabbri C; Polifemo AM; Zanini N; Pession A; Tallini G

RESUMEN / SUMMARY:  - KRAS is one of the most common genes mutated in pancreatic adenocarcinoma. Multiple KRAS mutations may be detected within the same pancreatic adenocarcinoma, but it is usually unclear whether the different mutations represent biologically irrelevant molecular events or whether they indicate the coexistence of distinct sizable neoplastic clones within a given tumor. We identified a case of pancreatic adenocarcinoma with 5 different mutations in the  KRAS gene and have been able to characterize the allelic distribution of the KRAS mutations and the size of the neoplastic clones using allele-specific locked nucleic acid polymerase chain reaction and next-generation sequencing (454 GS-Junior). The results indicate that the tumor is composed of 5 distinct cell populations: one is KRAS G12V mutated (~38% of neoplastic cells), the second is KRAS G12V in one allele and KRAS G12D in the other (~32%), the third is KRAS G12V in one allele and KRAS G12R in the other (~24%), and the fourth is KRAS G12V in one allele and KRAS G12C in the other (~6%). The fifth clone, representing a minority of neoplastic cells, has a KRAS Q61H mutation in addition to one of the  above alterations. Microsatellite analysis identified mutation of the NR21 marker out of the 13 tested, indicating that the tumor has a defect in maintaining DNA integrity different from loss of conventional DNA mismatch repair. These results  are consistent with the successive selection of divergent populations of tumor cells and underscore the relevance of nucleotide instability in pancreatic adenocarcinoma.

 

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[89]

TÍTULO / TITLE:  - Metabolomic and transcriptomic profiling of human K-ras oncogene transgenic rats  with pancreatic ductal adenocarcinomas.

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

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt053

AUTORES / AUTHORS:  - Yabushita S; Fukamachi K; Tanaka H; Fukuda T; Sumida K; Deguchi Y; Mikata K; Nishioka K; Kawamura S; Uwagawa S; Suzui M; B Alexander D; Tsuda H

INSTITUCIÓN / INSTITUTION:  - Environmental Health Science Laboratory, Sumitomo Chemical Co., Osaka 554-8558, Japan.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most debilitating malignancies in humans, and one of the reasons for this is the inability to diagnose this disease early in its development. To search for biomarkers that can be used for early diagnosis of PDAC, we established a rat model of human PDAC in  which expression of a human K-rasG12V oncogene and induction of PDAC are regulated by the Cre/lox system. In the present study, transgenic rats bearing PDAC and control transgenic rats with normal pancreatic tissues were used for metabolomic analysis of serum and pancreatic tissue by non-targeted and targeted  gas chromatography-mass spectrometry and transcriptomic analysis of pancreatic tissue by microarray. Comparison of the metabolic profiles of the serum and pancreatic tissue of PDAC-bearing and control rats identified palmitoleic acid as a metabolite, which was significantly decreased in the serum of PDAC-bearing animals. Transcriptomic analysis indicated that several transcripts involved in anaerobic glycolysis and nucleotide degradation were increased and transcripts involved in the trichloroacetic acid cycle were decreased. Other transcripts that were changed in PDAC-bearing rats were adenosine triphosphate citrate lyase (decreased: fatty acid biosynthesis), fatty acid synthase (increased: fatty acid  biosynthesis) and arachidonate 5-lipoxygenase activating protein (increased: arachidonic acid metabolism). Overall, our results suggest that the decreased serum levels of palmitoleic acid in rats with PDAC was likely due to its decrease in pancreatic tissue and that palmitoleic acid should be investigated in human samples to assess its diagnostic significance as a serum biomarker for human PDAC.

 

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[90]

TÍTULO / TITLE:  - Prognostic Significance of Autophagy-Related Protein Expression in Resected Pancreatic Ductal Adenocarcinoma.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279d0dc

AUTORES / AUTHORS:  - Ko YH; Cho YS; Won HS; Jeon EK; An HJ; Hong SU; Park JH; Lee MA

INSTITUCIÓN / INSTITUTION:  - From the Divisions of *Oncology and daggerGastroenterology, Department of Internal Medicine, Uijeongbu St Mary’s Hospital, Catholic University, Uijeongbu-si; double daggerDepartment of Maritime Medicine, Maritime Medical Center, Jinhae; section signDepartment of Biomedical Science, College of Medicine, Catholic University; and parallelDivision of Oncology, Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University, Seoul, South Korea.

RESUMEN / SUMMARY:  - OBJECTIVES: Autophagy is a critical intracellular pathway for the removal of aggregated proteins and damaged organelles. The aim of this study was to explore  the contribution of autophagy-related proteins to clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). METHODS: The expression of 5 autophagy-related proteins in the PDAC tissues of 73 patients was evaluated by  immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. RESULTS: Of the 73 patients, autophagy-related protein expression frequencies were 49.3% (36/73) for Atg5, 63.9% (46/72) for Ambra1, 47.9% (35/73) for beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was significant for all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (P = 0.059). Multivariate analysis revealed that beclin-1 overexpression and increases in the alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio of 5.365, P = 0.001 and hazard ratio of 5.270,  P = 0.022, respectively). CONCLUSIONS: The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The detection and inhibition of autophagy offers a potential therapeutic target for PDAC.

 

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[91]

TÍTULO / TITLE:  - Preoperative Histological Subtype Classification of Intraductal Papillary Mucinous Neoplasms (IPMN) by Pancreatic Juice Cytology With MUC Stain.

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

REVISTA / JOURNAL:  - Ann Surg. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e318281b824

AUTORES / AUTHORS:  - Hara T; Ikebe D; Odaka A; Sudo K; Nakamura K; Yamamoto H; Itami M; Hirata T; Kashimura J; Yamaguchi T

INSTITUCIÓN / INSTITUTION:  - *Division of Endoscopy, Chiba Cancer Center, Chiba, Japan daggerDivision of Gastroenterology, Chiba Cancer Center, Chiba, Japan double daggerDivision of Surgical Pathology, Chiba Cancer Center, Chiba, Japan section signDivision of Gastroenterological Surgery, Chiba Cancer Center, Chiba, Japan paragraph signInternal Medicine, Mito Saiseikai General Hospital, Ibaraki, Japan.

RESUMEN / SUMMARY:  - OBJECTIVE:: To prospectively evaluate the diagnostic value of preoperative histological subtyping of intraductal papillary mucinous neoplasms (IPMNs) by pancreatic juice cytology (PJC) with mucin (MUC) stain. BACKGROUND:: IPMNs are classified into four subtypes based on their histomorphology and mucin phenotype, and varied degrees of malignant nature and prognosis among these subtypes have been shown. METHODS:: The subjects were 36 patients with surgically confirmed IPMNs, who underwent PJC preoperatively by endoscopic retrograde cholangiopancreatography. Histological subtyping of cytological samples with or without MUC stain (MUC1, MUC2, and MUC5AC) was compared with that of resected specimens. RESULTS:: Histologically, low-grade dysplasia was found in 4 patients, intermediate in 10, high grade in 11, and invasive carcinoma in 11. Gastric, intestinal, pancreatobiliary, and oncocytic subtypes corresponded to 16, 14, 5, and 1 patient, respectively. The rate of high-grade dysplasia (HGD) and/or invasive IPMNs was 25% for gastric subtype, 85.7% for intestinal subtype, and 100% for both pancreatobiliary and oncocytic subtypes, showing a significant correlation between histological subtype and rate of HGD and/or invasive IPMN (P  < 0.01 for gastric vs nongastric).Histological subtype was successfully diagnosed by PJC in 42% (15/36) without MUC stain, and the rate was significantly improved  to 89% (32/36) with MUC stain (P < 0.01). The sensitivity, specificity, and overall accuracy of PJC with MUC stain were 86%, 100%, and 94% for intestinal subtype, respectively. When cytological grade was combined with MUC stain, the diagnosis of HGD/invasive IPMN showed 77.2% sensitivity, 85.7% specificity, and 80.5% accuracy. CONCLUSIONS:: Preoperative PJC with MUC stain proved to be highly reliable for identifying the histological subtype of IPMN and may provide useful  information for deciding surgical indication.

 

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[92]

TÍTULO / TITLE:  - Intraductal Papillary Mucinous Neoplasms of the Pancreas With Distinct Pancreatic Ductal Adenocarcinomas Are Frequently of Gastric Subtype.

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

REVISTA / JOURNAL:  - Ann Surg. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e31828cd008

AUTORES / AUTHORS:  - Ideno N; Ohtsuka T; Kono H; Fujiwara K; Oda Y; Aishima S; Ito T; Ishigami K; Tokunaga S; Ohuchida K; Takahata S; Nakamura M; Mizumoto K; Tanaka M

INSTITUCIÓN / INSTITUTION:  - Departments of *Surgery and Oncology, daggerAnatomic Pathology, double daggerMedicine and Bioregulatory Science, and, section signClinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, paragraph signMedical Information Center, Kyushu University Hospital, Fukuoka, Japan ||Department of Gastrointestinal Surgery, Kawasaki Medical School, Okayama, Japan.

RESUMEN / SUMMARY:  - OBJECTIVE:: To identify a high-risk group of patients with pancreatic ductal adenocarcinoma (PDAC), independently arising in the pancreas with intraductal papillary mucinous neoplasm (IPMN), using histopathologic subtypes. BACKGROUND::  Pathologic features of IPMN with distinct PDAC, including histopathologic subtypes of IPMN and PDAC phenotypes, have not been well characterized. Mucin expression patterns and the mutational status of GNAS and KRAS are useful to explore the relationship between these 2 lesion types. METHODS:: Clinicopathologic data of 179 resected IPMNs and 180 resected PDACs without IPMNs as a control group were reviewed. IPMNs were classified into 4 grades (low-grade, intermediate-grade, high-grade dysplasia, and an associated invasive carcinoma) and 4 subtypes (gastric, intestinal, pancreatobiliary, and oncocytic). The expression of MUC1, MUC2, MUC5AC, MUC6, and CDX2 was investigated by immunohistochemistry in IPMNs and PDACs with and without IPMNs. The mutational status of GNAS and KRAS was evaluated by cycle sequencing in PDACs and pre-/coexisting IPMNs. RESULTS:: Twenty-six synchronous or metachronous PDACs were identified in 20 patients (11.2%) with IPMNs. Occurrence of concomitant PDACs was more frequently observed in gastric-type IPMNs (18/110, 16.4%) compared with intestinal (1/49, 2.0%), pancreatobiliary (1/17, 5.9%), or oncocytic-type (0/3, 0%) (P = 0.047). Both PDACs with and without IPMNs were frequently positive for MUC1, MUC5AC, and MUC6 expression, as assessed by immunohistochemistry, but were negative for MUC2 and CDX2. The mucin-staining patterns were similar to those of invasive tubular adenocarcinoma arising from gastric-type IPMNs. Mutation of GNAS within codon 201 was not detected in PDACs and gastric-type IPMNs, whereas most of these exhibited KRAS mutations. However, the R201H GNAS mutation was detected in 1 intestinal-type IPMN with distinct PDAC. CONCLUSIONS:: Mucin expression patterns demonstrate that PDAC without GNAS mutations of an aggressive phenotype frequently arise in the pancreas with benign gastric-type IPMN in the absence of GNAS mutations.

 

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[93]

TÍTULO / TITLE:  - Treatment with the Radiolabelled Somatostatin Analog Lu-DOTATATE for Advanced Pancreatic Neuroendocrine Tumors.

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

REVISTA / JOURNAL:  - Neuroendocrinology. 2013 Feb 2.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000348394

AUTORES / AUTHORS:  - Sansovini M; Severi S; Ambrosetti A; Monti M; Nanni O; Sarnelli A; Bodei L; Garaboldi L; Bartolomei M; Paganelli G

INSTITUCIÓN / INSTITUTION:  - Unit of Radiometabolic Medicine, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola, Italy.

RESUMEN / SUMMARY:  - Background: We evaluated the activity and safety profile of (177)Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced G1-G2 pancreatic neuroendocrine tumors (P-NETs). Patients and Methods: Fifty-two consecutive patients were treated at two different therapeutic dosages of 18.5 GBq or 27.8 GBq in five cycles, according to the patient’s kidney function and bone marrow reserve, which are known to be the critical organs in PRRT. Results:  Twenty-six patients received a mean full dosage (FD) of 25.5 GBq (range 20.7-27.8) and 26 a mean reduced dosage (RD) of 17.8 GBq (range 11.1-19.9). Both  therapeutic dosages resulted in antitumor activity (Disease Control Rate in the entire case series 81%), with 12% complete response (CR), 27% partial response (PR) and 46% stable disease (SD) in the FD group, whereas we observed 4% CR, 15%  PR and 58% SD in the RD group. Median progression-free survival (PFS) was not reached in the FD group and was 20 months in the RD group. No major acute or delayed hematological toxicity occurred. Conclusion: Lu-PRRT showed antitumor activity in advanced P-NETs even at a reduced total activity of 18.5 GBq. However, PFS was significantly longer (p = 0.05) after a total activity of 27.8 GBq, which can thus be considered the recommended dosage in eligible patients.

 

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[94]

TÍTULO / TITLE:  - Prognostic factors in gemcitabine-cisplatin polychemotherapy regimens in pancreatic cancer: XPD-Lys751Gln polymorphism strikes back.

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

REVISTA / JOURNAL:  - Int J Cancer. 2013 Feb 7. doi: 10.1002/ijc.28078.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28078

AUTORES / AUTHORS:  - Avan A; Pacetti P; Reni M; Milella M; Vasile E; Mambrini A; Vaccaro V; Caponi S; Cereda S; Peters GJ; Cantore M; Giovannetti E

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.

RESUMEN / SUMMARY:  - The use of platinated agents in combination chemotherapy regimens for advanced pancreatic cancer is controversial owing to the lack of an outstanding impact on  the outcome and a substantial increase in hematologic and extra-hematologic toxicities. Pharmacogenetic studies to identify patients who could benefit most from such therapies are urgently needed. The Xeroderma-Pigmentosum group-D polymorphism at codon-751 (XPD-Lys751Gln) emerged as the most significant independent predictor for death- and progression-risk in our previous study on functional polymorphisms in 122 advanced pancreatic cancer patients treated with  cisplatin-docetaxel-capecitabine-gemcitabine and cisplatin-epirubicin-capecitabine-gemcitabine (or EC-GemCap). To confirm the prognostic role of this variable, we further evaluated the correlation of XPD-Lys751Gln with outcome in another 125 patients treated with the same regimens, and 90 treated with gemcitabine monotherapy. Genotyping was successfully carried out in the vast majority of DNA samples. Genotype frequencies followed Hardy-Weinberg equilibrium, and XPD-Lys751Gln was associated with differential progression-free and overall-survival. Multivariate analysis confirmed its prognostic significance in platinum-based regimens. In particular,  XPD-Gln751Gln was significantly associated with risk of death (hazard ratio, HR = 1.7, 95% confidence interval [CI], 1.1-2.6, p = 0.011) and risk of progression (HR = 1.7, 95% CI, 1.1-2.5, p = 0.013). No correlation was observed in gemcitabine monotherapy-treated patients. The analysis of DNA damage using extra-long-PCR in lymphocytes supported the association of XPD-Gln751Gln with greater resistance to cisplatin-induced damage. The increasing evidence of XPD-Lys751Gln impact on the outcome of gemcitabine-cisplatin-based polychemotherapy leads to plan prospective studies to validate the role of this polymorphism as a new tool for optimization of the currently available treatments in pancreatic cancer.

 

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[95]

TÍTULO / TITLE:  - miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Feb 21. doi: 10.3892/or.2013.2297.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2297

AUTORES / AUTHORS:  - Cai B; An Y; Lv N; Chen J; Tu M; Sun J; Wu P; Wei J; Jiang K; Miao Y

INSTITUCIÓN / INSTITUTION:  - Institute of Tumor Biology, Jiangsu Province Academy of Clinical Medicine, Nanjing, Jiangsu 210029, P.R. China.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease and is usually resistant to chemotherapy. MicroRNA181b (miR-181b) has been reported to be associated with chemoresistance in various types of cancer. In this study, we investigated the effects of miR-181b on the chemosensitivity of PDAC cells to gemcitabine and the underlying molecular events. miR-181b mimics and inhibitors were synthesized for transient gene transfection in vitro. Lentivirus carrying miR-181b mimics were used to infect PDAC cells for nude mouse xenograft assays by implanting infected PDAC cells into recipient mice. Cell viability was determined by MTT assays, while gene expression was assessed using qRT-PCR, western blot analysis and enzyme-linked immunosorbent assay (ELISA). miR-181b targeting BCL-2  expression was assessed by a dual-luciferase activity assay. The data showed that miRNA-181b expression sensitized PDAC cells to gemcitabine treatment. Although gemcitabine-resistant PDAC cell sublines (SW1990/GR and CFPAC-1/GR) expressed higher levels of miRNA-181b, gemcitabine induced higher levels of apoptosis in PDAC cells transfected with miRNA-181b mimics. The nude mouse xenograft assay data showed that miR-181b transfection also sensitized the cells to gemcitabine treatment in vivo. Molecularly, bioinformatics data predicted that miR-181b was able to bind to BCL-2 mRNA 3’UTR. The dual luciferase activity assay revealed that miRNA-181b downregulated BCL-2 expression. The results from western blot analysis showed a reduced BCL-2 expression following miR-181b transfection but an enhanced caspase-3 activity in miRNA-181b mimic-transfected PDAC cells. This study demonstrates that miRNA-181b sensitizes PDAC cells to gemcitabine by targeting BCL-2.

 

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[96]

TÍTULO / TITLE:  - Evolution and dynamics of pancreatic cancer progression.

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

REVISTA / JOURNAL:  - Oncogene. 2013 Feb 18. doi: 10.1038/onc.2013.29.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.29

AUTORES / AUTHORS:  - Yachida S; Iacobuzio-Donahue CA

INSTITUCIÓN / INSTITUTION:  - 1] Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA [2] Division of Refractory Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.

RESUMEN / SUMMARY:  - Efficient metastasis is believed as the result of multiple genetic, epigenetic and/or post-translational events in the lifetime of a carcinoma. At the genetic level, these events may be categorized into those that occur during carcinogenesis, and those that occur during subclonal evolution. This review summarizes current knowledge of the genetics of pancreatic cancer from its initiation within a normal cell until the time that is has disseminated to distant organs, many features of which can be extrapolated to other solid tumor types. The implications of these findings to personalize genome analyses of an individual patient’s tumor are also discussed.Oncogene advance online publication, 18 February 2013; doi:10.1038/onc.2013.29.

 

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[97]

TÍTULO / TITLE:  - The differential diagnosis of squamous cells in pancreatic aspirates: from contamination to adenosquamous carcinoma.

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

REVISTA / JOURNAL:  - Acta Cytol. 2013;57(2):139-46. doi: 10.1159/000346326. Epub 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000346326

AUTORES / AUTHORS:  - Olson MT; Siddiqui MT; Ali SZ

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.

RESUMEN / SUMMARY:  - BACKGROUND: This study was conducted to describe the frequency and significance of squamous cells in fine needle aspiration (FNA) specimens of the pancreas in benign and malignant processes. METHODS: A retrospective review was performed of  102 patients with squamous cells in their pancreatic FNA specimens from 1986 to 2012. The malignant cases were classified as adenosquamous carcinoma (ASqC) or metastatic squamous cell carcinoma, and a double institutional review of the ASqC cases was undertaken to characterize the clinical and pathological features and survival statistics of patients who present with unresectable or metastatic ASqC  and have no follow-up surgery. Survival analyses were performed. RESULTS: Of the  4,094 pancreas FNA procedures performed in the study, squamous features were found in 102 (2.5%) of all cases, and 48% of these cases represented ASqC. The other cases were contamination (52%) or atypical (<1%). ASqC constituted 4.5% (46/1,025) of all primary pancreatic exocrine malignancies. When compared with conventional adenocarcinoma, ASqC demonstrated a significantly poorer overall median survival (11.0 vs. 6.51 months; p = 0.023), and this difference was also seen in patients presenting with metastatic disease (median survival of 9.1 vs. 4.2 months; p = 0.025). CONCLUSIONS: Squamous cells in FNA specimens from the pancreas have a broad differential diagnosis that ranges from contamination to ASqC.

 

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[98]

TÍTULO / TITLE:  - The Differentiation of Pancreatic Tumor-Initiating Cells by Vitronectin Can Be Blocked by Cilengitide.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279d568

AUTORES / AUTHORS:  - Cabarcas SM; Sun L; Mathews L; Thomas S; Zhang X; Farrar WL

INSTITUCIÓN / INSTITUTION:  - From the *Cancer Stem Cell Section, Laboratory of Cancer Prevention, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick; daggerNational Center for Translational Therapeutics, National Chemical Genomics  Center National Human Genome Research Institute, Rockville; double daggerMedImmune, Gaithersburg; and section signSAIC-Frederick Inc, Frederick National Laboratory for Cancer Research, Frederick, MD.

RESUMEN / SUMMARY:  - OBJECTIVE: Pancreatic cancer is a leading cancer type and its molecular pathology is poorly understood. The only potentially curative therapeutic option available  is complete surgical resection; however, this is inadequate as most of the patients are diagnosed at an advanced or metastatic stage. Tumor-initiating cells (TICs) constitute a subpopulation of cells within a solid tumor that sustain tumor growth, metastasis, and chemo/radioresistance. Within pancreatic cancer, TICs have been identified based on the expression of specific cell surface markers. METHODS: We use a sphere formation assay to enrich putative TICs and use human serum as a driver of differentiation. We demonstrate by using specific blocking reagents that we can inhibit the differentiation process and maintain TIC-associated markers and genes. RESULTS: We can induce differentiation of pancreatospheres with the addition of human serum, and we identified vitronectin  as an inducer of differentiation. We inhibit differentiation by human serum using an arginine-glycine-aspartate-specific peptide, which is Cilengitide; hence, demonstrating this differentiation is mediated via specific integrin receptors. CONCLUSIONS: Overall, our studies further the definition of pancreatic TICs and provide further insight into both the maintenance and differentiation of this lethal population.

 

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[99]

TÍTULO / TITLE:  - Use of EUS-FNA in diagnosing pancreatic neoplasm without a definitive mass on CT.

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

REVISTA / JOURNAL:  - Gastrointest Endosc. 2013 Mar 21. pii: S0016-5107(13)00097-7. doi: 10.1016/j.gie.2013.01.040.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gie.2013.01.040

AUTORES / AUTHORS:  - Wang W; Shpaner A; Krishna SG; Ross WA; Bhutani MS; Tamm EP; Raju GS; Xiao L; Wolff RA; Fleming JB; Lee JH

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Hepatology, and Nutrition, MD Anderson Cancer Center, Houston, Texas, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Diagnosis of pancreatic neoplasm is challenging in patients with inconclusive findings on pancreatic multidetector row CT (MDCT). OBJECTIVE: To determine the diagnostic accuracy and to identify predictors of pancreatic neoplasm by EUS with FNA in this setting. DESIGN: Retrospective chart review during the study period of January 2002 to December 2010. SETTING: Tertiary referral center. PATIENTS: Of the 1046 patients who underwent pancreatic EUS, 116 patients were selected because their clinical presentation was suspicious for pancreatic malignancy, but their MDCT findings were inconclusive. INTERVENTION: EUS with FNA. MAIN OUTCOME MEASUREMENTS: Diagnostic yield of malignancy and significance of clinical variables. RESULTS: When surgical pathology or subsequent clinical course was used as the criterion standard, EUS with FNA had a sensitivity, specificity, positive predictive value, and accuracy of 87.3%, 98.3%, 98.5%, and 92.1%, respectively, in diagnosing a pancreatic neoplasm that was indeterminate on MDCT. Factors significantly associated with EUS detection of pancreatic ductal adenocarcinoma were total bilirubin level greater than 2 mg/dL  (P < .001), CT finding of pancreatic duct dilation (P < .001), bile duct stricture (P < .001), and tumor size 1.5 cm or larger detected by EUS (P = .004). Among them, pancreatic duct dilation on CT (odds ratio 4.10; 95% confidence interval, 1.52-11.05), and tumor size 1.5 cm or larger detected by EUS (odds ratio 8.46; 95% confidence interval, 2.02-35.45) were independent risk factors. LIMITATIONS: Retrospective design and patient referral bias. CONCLUSIONS: When MDCT is indeterminate, EUS is a highly sensitive and accurate modality for the detection of pancreatic neoplasm, especially when the tumor is smaller than 2.0 cm.

 

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[100]

TÍTULO / TITLE:  - Synthesis and evaluation of cholecystokinin trimers: A multivalent approach to pancreatic cancer detection and treatment.

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

REVISTA / JOURNAL:  - Bioorg Med Chem Lett. 2013 Apr 15;23(8):2422-5. doi: 10.1016/j.bmcl.2013.02.022.  Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bmcl.2013.02.022

AUTORES / AUTHORS:  - Brabez N; Nguyen KL; Saunders K; Lacy R; Xu L; Gillies RJ; Lynch RM; Chassaing G; Lavielle S; Hruby VJ

INSTITUCIÓN / INSTITUTION:  - UPMC Paris 06, UMR 7203, Laboratoire des BioMolecules, Universite P. et M. Curie, 75005 Paris, France; CNRS, UMR 7203, France; ENS, UMR 7203, Departement de Chimie, Ecole Normale Superieure, 75005 Paris, France; University of Arizona, Department of Chemistry and Biochemistry, Tucson, AZ 85721, USA.

RESUMEN / SUMMARY:  - In the quest for novel tools for early detection and treatment of cancer, we propose the use of multimers targeting overexpressed receptors at the cancer cell surface. Indeed, multimers are prone to create multivalent interactions, more potent and specific than their corresponding monovalent versions, thus enabling the potential for early detection. There is a lack of tools for early detection of pancreatic cancer, one of the deadliest forms of cancer, but CCK2-R overexpression on pancreatic cancer cells makes CCK based multimers potential markers for these cells. In this Letter, we describe the synthesis and evaluation of CCK trimers targeting overexpressed CCK2-R.

 

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[101]

TÍTULO / TITLE:  - Prognosis of Minimally Invasive Carcinoma Arising in Mucinous Cystic Neoplasms of the Pancreas.

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

REVISTA / JOURNAL:  - Am J Surg Pathol. 2013 Apr;37(4):601-605.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e318273f3b0

AUTORES / AUTHORS:  - Lewis GH; Wang H; Bellizzi AM; Klein AP; Askin FB; Schwartz LE; Schulick RD; Wolfgang CL; Cameron JL; O’Reilly EM; Yu KH; Hruban RH

INSTITUCIÓN / INSTITUTION:  - Departments of *Pathology parallelEpidemiology paragraph signOncology **Surgery,  The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD daggerDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX double daggerDepartment of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA section signDepartment of Pathology, Brigham and Women’s Hospital, Boston, MA #Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA daggerdaggerDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.

RESUMEN / SUMMARY:  - Although patients with surgically resected noninvasive mucinous cystic neoplasms  (MCNs) of the pancreas are cured, the behavior of surgically resected minimally invasive adenocarcinomas arising in MCN has not been well established. We report  16 surgically resected MCNs with minimal invasion defined as unifocal or multifocal microscopic invasive adenocarcinoma confined to the ovarian stroma of  the MCN without capsular or pancreatic parenchymal invasion. Pathologic findings  were correlated with patient demographics, type of surgery, and long-term follow-up. Our study included 15 women and 1 man ranging in age from 25 to 66 years. The patients were followed up for a mean of 48.6 months (range, 12 to 148  mo). The MCNs ranged in size from 3.5 to 25 cm and were all located in the body/tail of the gland. Lymphovascular invasion was not identified in any of the  cases, and all lymph nodes were negative for tumor. Ten neoplasms had unifocal invasion, whereas 6 had multifocal invasion. Twelve of the neoplasms were partially submitted for microscopic examination, whereas 4 were submitted entirely. Only 1 of the 16 minimally invasive MCNs recurred, and that tumor had been lighlty sampled pathologically. Our study demonstrates that the majority of  patients with minimally invasive adenocarcinoma arising in MCNs are cured by surgery, particularly if the neoplasms are completely examined histologically.

 

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[102]

TÍTULO / TITLE:  - Senescence in pancreatic carcinogenesis: from signalling to chromatin remodelling and epigenetics.

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

REVISTA / JOURNAL:  - Gut. 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1136/gutjnl-2012-302793

AUTORES / AUTHORS:  - Singh SK; Ellenrieder V

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Philipps University of Marburg, , Marburg, Germany.

RESUMEN / SUMMARY:  - Mutational activation of K-Ras is a key genetic event involved in the initiation  of pancreatic carcinogenesis. However, K-Ras generally fails to transform precursor lesions into invasive cancers due to activation of powerful fail-safe programmes that counteract transformation and growth. The importance of cellular  senescence, a permanent cell growth arrest, is increasingly being recognised as a critical fail-safe programme in pancreatic carcinogenesis. Emerging evidence suggests that oncogene-induced senescence requires transcriptional induction of the CDKN2A gene locus as well as comprehensive chromatin modifications involved in epigenetic silencing of pro-proliferative genes. Moreover, recent work in pancreatic cancer mouse models proposes that inactivation of the CDKN2A tumour suppressor locus is the molecular switch required for senescence evasion and unleashed K-Ras driven malignant transformation in the pancreas.

 

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[103]

TÍTULO / TITLE:  - Molecular analysis of the inhibitory effect of N-acetyl-L-cysteine on the proliferation and invasiveness of pancreatic cancer cells.

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

REVISTA / JOURNAL:  - Anticancer Drugs. 2013 Jun;24(5):504-18. doi: 10.1097/CAD.0b013e32836009d7.

            ●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32836009d7

AUTORES / AUTHORS:  - Mezencev R; Wang L; Xu W; Kim B; Sulchek TA; Daneker GW; McDonald JF

INSTITUCIÓN / INSTITUTION:  - aSchool of Biology and the Petit Institute of Bioengineering and Bioscience bThe  George W. Woodruff School of Mechanical Engineering cThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta dCancer Treatment Centers of America, Newnan, Georgia, USA.

RESUMEN / SUMMARY:  - Preliminary studies have suggested that the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) may be effective in inhibiting the growth of  pancreatic cancer cells. In-depth cellular and molecular analyses were carried out to determine NAC’s mode of action in inhibiting the growth of a well-characterized pancreatic cancer cell line (AsPC-1). Standardized assays were used to monitor cellular growth, apoptosis, levels of ROS, cellular senescence, migration, and invasiveness. Cell stiffness was measured using atomic force microscopy. Gene expression was monitored by quantitative PCR. NAC significantly  inhibits the growth and metastatic potential of AsPC-1 cells by inducing cell-cycle arrest in G1 and subsequent cellular senescence and decreased invasiveness. These anticancer properties are associated with an unexpected increase in the intracellular concentrations of ROS. NAC does not decrease the susceptibility of AsPC-1 cells to the anticancer drugs gemcitabine, mitomycin C,  and doxorubicin. NAC-induced changes in gene expression are consistent with the onset of mesenchymal-to-epithelial transition. In conclusion, our findings indicate that NAC induces an integrated series of responses in AsPC-1 cells that  make it a highly promising candidate for development as a pancreatic cancer therapeutic.

 

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[104]

TÍTULO / TITLE:  - A comparison between intraductal papillary neoplasms of the biliary tract (BT-IPMNs) and intraductal papillary mucinous neoplasms of the pancreas (P-IPMNs) reveals distinct clinical manifestations and outcomes.

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

REVISTA / JOURNAL:  - Eur J Surg Oncol. 2013 Mar 15. pii: S0748-7983(13)00261-8. doi: 10.1016/j.ejso.2013.02.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejso.2013.02.016

AUTORES / AUTHORS:  - Minagawa N; Sato N; Mori Y; Tamura T; Higure A; Yamaguchi K

INSTITUCIÓN / INSTITUTION:  - Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Intraductal papillary mucinous neoplasm of the biliary tract (BT-IPMN) has been increasingly recognized as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas (P-IPMN). However, there  is limited information regarding whether BT-IPMNs and P-IPMNs behave in a similar fashion. METHODS: We retrospectively compared clinicopathological variables between 9 patients with BT-IPMN and 44 patients with P-IPMN. RESULTS: There was no significant difference in age between patients with BT-IPMN and those with P-IPMN. The male/female ratio was significantly higher in patients with P-IPMN than in those with BT-IPMN (P = 0.012). Clinical presentation with jaundice was more common in patients with BT-IPMN (67%) than in those with P-IPMN (4.5%, P = 0.002). In addition, serum levels of CEA and CA19-9 were higher in patients with  BT-IPMN than in those with P-IPMN (P = 0.019 and P = 0.002, respectively). The pathological diagnosis of malignancy was significantly more common in patients with BT-IPMN (89%) than in those with P-IPMN (23%, P = 0.002). The association with invasive carcinoma was significantly more frequent in patients with BT-IPMN  (44.4%) than in those with P-IPMN (6.8%, P = 0.008). Furthermore, survival time after surgical resection was significantly shorter in patients with BT-IPMN than  in those with P-IPMN (P = 0.002). CONCLUSION: These findings reveal differences in clinicopathological features and prognosis between BT-IPMN and P-IPMN, thereby suggesting distinct biological pathways underlying the pathogenesis of these neoplasms.

 

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[105]

TÍTULO / TITLE:  - Systemic delivery of gemcitabine triphosphate via LCP nanoparticles for NSCLC and pancreatic cancer therapy.

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

REVISTA / JOURNAL:  - Biomaterials. 2013 Apr;34(13):3447-58. doi: 10.1016/j.biomaterials.2013.01.063. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.01.063

AUTORES / AUTHORS:  - Zhang Y; Kim WY; Huang L

INSTITUCIÓN / INSTITUTION:  - Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA.

RESUMEN / SUMMARY:  - Nucleoside analogs are a significant class of anti-cancer agent. As prodrugs, they terminate the DNA synthesis upon transforming to their active triphosphate metabolites. We have encapsulated a biologically activate nucleotide analog (i.e. gemcitabine triphosphate (GTP)), instead of the nucleoside (i.e. gemcitabine) derivative, into a novel Lipid/Calcium/Phosphate nanoparticle (LCP) platform. The therapeutic efficacy of LCP-formulated GTP was evaluated in a panel of human non-small-cell lung cancer (NSCLC) and human pancreatic cancer models after systemic administrations. GTP-loaded LCPs induced cell death and arrested the cell cycle in the S phase. In vivo efficacy studies showed that intravenously injected GTP-loaded LCPs triggered effective apoptosis of tumor cells, significant reduction of tumor cell proliferation and cell cycle progression, leading to dramatic inhibition of tumor growth, with little in vivo toxicity. Broadly speaking, the current study offers preclinical proof-of-principle that many active nucleotide or phosphorylated nucleoside analogs could be encapsulated in the LCP nanoplatform and delivered systemically for a wide variety of therapeutic applications.

 

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[106]

TÍTULO / TITLE:  - MicroRNA-100 regulates IGF1-receptor expression in metastatic pancreatic cancer cells.

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

REVISTA / JOURNAL:  - Biotech Histochem. 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 3109/10520295.2012.762460

AUTORES / AUTHORS:  - Huang J; Egger M; Grizzle W; McNally L

INSTITUCIÓN / INSTITUTION:  - University of Louisville , Louisville , Kentucky.

RESUMEN / SUMMARY:  - Patients with pancreatic adenocarcinoma have the lowest 5 year survival rate and  yearly rates of incidence are nearly equal to the mortality rates. Long term cure rates by standard therapies are disappointing owing to disseminated disease at diagnosis and chemotherapeutic resistance. New therapeutic targets are necessary  to decrease the progression of pancreatic cancer and the ability to identify targets specific to metastasis would improve patient care. We evaluated the levels of microRNA of metastatic and non-metastatic cell lines. The expression levels of microRNAs and mRNAs were determined using microarray analysis to examine and compare five pancreatic cancer cell lines, two that can metastasize in vivo (S2VP10 and S2CP9) and three that do not metastasize (MiaPaCa2, Panc-1 and ASPC-1). MicroRNA analysis indicated an increase in miR-100 and a decrease in miR-138 expression in metastatic cancer cells. Microarray analysis of different expressions of mRNAs in metastatic and non-metastatic pancreatic cell lines also  indicated significantly increased insulin growth factor-1 receptor (IGF1-R) expression in metastatic pancreatic cancer cell lines compared to non-metastatic  pancreatic cancer cell lines. To confirm microarray analysis results, western blot and immunocytochemistry were performed. Western blot revealed that IGF1-R expression exhibited in metastatic cancer cell lines a seven-fold increase compared to non-metastatic cell lines. In addition, downstream expressions of the proteins, GRB2 and phosphorylated PI3K, also were increased in aggressive cancer  cell lines. Immunocytochemistry confirmed the linkage of IGF1-R to miR-100, because cells transfected with miR-100 inhibitor showed a decrease in IGF1-R. Cells transfected with a miR-138 mimic, however, did not affect IGF1-R expression.

 

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[107]

TÍTULO / TITLE:  - Lactate dehydrogenase A is overexpressed in pancreatic cancer and promotes the growth of pancreatic cancer cells.

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

REVISTA / JOURNAL:  - Tumour Biol. 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0679-1

AUTORES / AUTHORS:  - Rong Y; Wu W; Ni X; Kuang T; Jin D; Wang D; Lou W

INSTITUCIÓN / INSTITUTION:  - Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan University, 180th Feng Lin Road, Shanghai, 200031, China.

RESUMEN / SUMMARY:  - The prognosis for pancreatic cancer is very poor, and developing new therapeutic  strategies for this cancer is needed. Recently, the Warburg effect (aerobic glycolysis) has attracted much attention for its function in the tumorigenesis. Lactate dehydrogenase A (LDHA) executes the final step of aerobic glycolysis and  has been reported to be involved in the tumor progression. However, the function  of LDHA in pancreatic cancer has not been studied. Here, we found that the expression of LDHA was elevated in the clinical pancreatic cancer samples. Forced expression of LDHA promoted the growth of pancreatic cancer cells, while knocking down the expression of LDHA inhibited cell growth dramatically. Moreover, silencing the expression of LDHA inhibited the tumorigenicity of pancreatic cancer cells in vivo. Mechanistically, knocking down the expression of LDHA activated apoptosis pathway. Taken together, our study revealed the oncogenic role of LDHA in pancreatic cancer and suggested that LDHA might be a potential therapeutic target.

 

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[108]

TÍTULO / TITLE:  - The gep Proto-Oncogene Galpha13 Mediates Lysophosphatidic Acid-Mediated Migration of Pancreatic Cancer Cells.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279c577

AUTORES / AUTHORS:  - Gardner JA; Ha JH; Jayaraman M; Dhanasekaran DN

INSTITUCIÓN / INSTITUTION:  - From the *Penn State Milton S. Hershey Medical Center, Hershey, PA; daggerCollege of Pharmacy, Seoul National University, Seoul, Republic of Korea; and double daggerPeggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK.

RESUMEN / SUMMARY:  - OBJECTIVES: Tumor microenvironment, defined by a variety of growth factors including lysophosphatidic acid (LPA), whose levels are increased in pancreatic cancer patients, plays a major role in the genesis and progression of pancreatic  cancer. Because the gep proto-oncogenes, Galpha12 and Galpha13, are implicated in LPA-stimulated oncogenic signaling, this study is focused on evaluating the role  of these proto-oncogenes in LPA-stimulated invasive migration of pancreatic cancer cells. METHODS: Effect of LPA on the migration and proliferation of pancreatic cancer cells was assessed using BxPC3, Dan-G, MDAPanc-28, Panc-1, and  PaCa-2 cell lines. The role of Galpha13 in the migration of pancreatic cancer cells was interrogated by disrupting lysophosphatidic acid receptor-Galpha13 interaction using CT13, a dominant negative mutant of Galpha13, and by silencing  the expression of Galpha13. RESULTS: Results indicate that LPA stimulates the migration of pancreatic cancer cells and such LPA-stimulated migratory response is mediated by Galpha13. Furthermore, the results establish that the silencing of Galpha13, but not Galpha12, abrogates LPA-stimulated invasive migration of pancreatic cancer cells. CONCLUSIONS: These results report for the first time a critical role for Galpha13 in LPA-stimulated invasive migration of pancreatic cancer cells. These findings identify LPA-lysophosphatidic acid receptor-Galpha13 signaling node as a novel therapeutic target for pancreatic cancer treatment and  control.

 

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[109]

TÍTULO / TITLE:  - Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer.

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

REVISTA / JOURNAL:  - Cancer Lett. 2013 Feb 10. pii: S0304-3835(13)00119-5. doi: 10.1016/j.canlet.2013.01.054.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.054

AUTORES / AUTHORS:  - Yabuuchi S; Pai SG; Campbell NR; de Wilde RF; De Oliveira E; Korangath P; Streppel MM; Rasheed ZA; Hidalgo M; Maitra A; Rajeshkumar NV

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore,  MD, USA. Electronic address: s1-yabuuchi@surg1.med.tohoku.ac.jp.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDA) remains a lethal human malignancy with historically limited success in treatment. The role of aberrant Notch signaling,  which requires the constitutive activation of gamma-secretase, in the initiation  and progression of PDA is well defined and inhibitors of this pathway are currently in clinical trials. Here we investigated the in vivo therapeutic effect of PF-03084014, a selective gamma-secretase inhibitor, alone and in combination with gemcitabine in pancreatic cancer xenografts. PF-03084014 treatment inhibited the cleavage of nuclear Notch 1 intracellular domain and Notch targets Hes-1 and  Hey-1. Gemcitabine treatment showed good response but not capable of inducing tumor regressions and targeting the tumor-resident cancer stem cells (CD24(+)CD44(+) and ALDH(+) tumor cells). A combination of PF-03084014 and gemcitabine treatment resulted tumor regression in 3 of 4 subcutaneously implanted xenograft models. PF-03084014, and in combination with gemcitabine reduced putative cancer stem cells, indicating that PF-03084014 target the especially dangerous and resilient cancer stem cells within pancreatic tumors. Tumor re-growth curves plotted after drug treatments demonstrated that the effect of the combination therapy was sustainable than that of gemcitabine. Notably, in  a highly aggressive orthotopic model, PF-03084014 and gemcitabine combination was effective in inducing apoptosis, inhibition of tumor cell proliferation and angiogenesis, resulting in the attenuation of primary tumor growth as well as controlling metastatic dissemination, compared to gemcitabine treatment. In summary, our preclinical data suggest that PF-03084014 has greater anti-tumor activity in combination with gemcitabine in PDA and provides rationale for further investigation of this combination in PDA.

 

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[110]

TÍTULO / TITLE:  - Interfractional dose variations in the stomach and the bowels during breathhold intensity-modulated radiotherapy for pancreatic cancer: Implications for a dose-escalation strategy.

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

REVISTA / JOURNAL:  - Med Phys. 2013 Feb;40(2):021701. doi: 10.1118/1.4773033.

            ●● Enlace al texto completo (gratuito o de pago) 1118/1.4773033

AUTORES / AUTHORS:  - Nakamura A; Shibuya K; Nakamura M; Matsuo Y; Shiinoki T; Nakata M; Mizowaki T; Hiraoka M

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology and Image-applied Therapy, Kyoto University, Kyoto, Japan.

RESUMEN / SUMMARY:  - PURPOSE: This study aims to evaluate the interfractional dose variations in the organs-at-risk (OARs) during pancreatic breathhold intensity-modulated radiotherapy (IMRT) and to assess the impacts of “planning organs-at-risk volume” (POV) structures generated by isotropically expanding the dose-limiting OARs, based on the comparison of the interfractional doses to the OARs between IMRT plans and conventional three-dimensional-conformal radiotherapy (3D-CRT) plans. METHODS: Thirty repeat CT scans were acquired from ten consecutive patients who were receiving chemoradiotherapy for pancreatic cancer. Six IMRT plans for each patient with two levels of prescription (45 and 51 Gy in 15 fractions) and 3 POV  margin sizes (5, 7, and 10 mm) were generated based on the initial CT scan under  predetermined constraints. Two 3D-CRT plans (39 and 42 Gy in 15 fractions) were simultaneously generated. The dose distribution of all of the treatment plans was recalculated with the repeat CT scans. The interfractional dose variations in the three OARs (stomach, duodenum, and small intestine) were evaluated, and the absolute volumes >/=39 Gy (V39Gy) of the OARs in the IMRT plans were compared to  those in the 3D-CRT plans. Regression analyses were performed to assess the relative impact of the factors of interest on the interfractional dose variations of the OARs. RESULTS: Substantial dose excesses to the three OARs were observed at all of the prescription dose levels and the POV margin sizes on the repeat CT  scans. The safety threshold based on the mean stomach V39Gy on the recalculated 39 Gy-3D-CRT plans was 1.9 ml. Statistically significant and marginally insignificant mean V39Gy values above the safety thresholds were observed in the  stomach in the 51 Gy-IMRT plans (2.6 and 2.1 ml with the 5- and 7-mm PRV margins, respectively (P = 0.015 and 0.085)). Only in the case of the 10-mm POV margin did the metric fall below the safety threshold to 1.5 ml (P = 0.634). The duodenum and the small intestine did not violate the safety thresholds (1.4 and 3.8 ml, respectively). From the multiple regression analyses, only the margin size (P < 0.001) and the POV V39Gy (P < 0.001) were significantly associated with the distribution of recalculated V39Gy for the stomach. Multiple factors, including the margin size (P = 0.020) and the POV V39Gy (P < 0.001) were associated with the recalculated V39Gy for the duodenum. However, none of the POV parameters for  the small intestine were associated with the recalculated V39Gy. CONCLUSIONS: Considerable interfractional dose variation was observed in three critical OARs.  At the escalated prescription dose of breathhold IMRT, the dose variations could  exceed the dose variations using 3D-CRT at the safe prescription dose level, indicating that a dose-escalation strategy based solely on the initial advantageous dose distribution in a breathhold IMRT can be problematic. Given the current limitations for predicting or coping with variation throughout the treatment course, the use of POV should be considered for safely delivering escalated doses to patients with pancreatic cancer.

 

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[111]

TÍTULO / TITLE:  - ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin.

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

REVISTA / JOURNAL:  - Mod Pathol. 2013 Mar 15. doi: 10.1038/modpathol.2013.40.

            ●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2013.40

AUTORES / AUTHORS:  - Agaimy A; Erlenbach-Wunsch K; Konukiewitz B; Schmitt AM; Rieker RJ; Vieth M; Kiesewetter F; Hartmann A; Zamboni G; Perren A; Kloppel G

INSTITUCIÓN / INSTITUTION:  - Institute of Pathology, University Hospital, Erlangen, Germany.

RESUMEN / SUMMARY:  - The human insulin gene enhancer-binding protein islet-1 (ISL1) is a transcription factor involved in the differentiation of the neuroendocrine pancreatic cells. Recent studies identified ISL1 as a marker for pancreatic well-differentiated neuroendocrine neoplasms. However, little is known about ISL1 expression in pancreatic poorly differentiated and in extrapancreatic well and poorly differentiated neuroendocrine neoplasms. We studied the immunohistochemical expression of ISL1 in 124 neuroendocrine neoplasms. Among pancreatic neuroendocrine neoplasms, 12/13 with poor differentiation were negative, whereas  5/7 with good differentiation but a Ki67 >20% were positive. In extrapancreatic neuroendocrine neoplasms, strong positivity was found in Merkel cell carcinomas (25/25), pulmonary small cell neuroendocrine carcinomas (21/23), medullary thyroid carcinomas (9/9), paragangliomas/pheochromocytomas (6/6), adrenal neuroblastomas (8/8) and head and neck neuroendocrine carcinomas (4/5), whereas no or only weak staining was recorded in pulmonary carcinoids (3/15), olfactory neuroblastomas (1/4) and basaloid head and neck squamous cell carcinomas (0/15).  ISL1 stained the neuroendocrine carcinoma component of 5/8 composite carcinomas and also normal neuroendocrine cells in the thyroid, adrenal medulla, stomach and colorectum. Poorly differentiated neuroendocrine neoplasms, regardless of their ISL1 expression, were usually TP53 positive. Our results show the almost ubiquitous expression of ISL1 in extrapancreatic poorly differentiated neuroendocrine neoplasms and neuroblastic malignancies and its common loss in pancreatic poorly differentiated neuroendocrine neoplasms. These findings modify  the role of ISL1 as a marker for pancreatic neuroendocrine neoplasms and suggest  that ISL1 has a broader involvement in differentiation and growth of neuroendocrine neoplasms than has so far been assumed.Modern Pathology advance online publication, 15 March 2013; doi:10.1038/modpathol.2013.40.

 

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[112]

TÍTULO / TITLE:  - Sunitinib for the Treatment of Metastatic Paraganglioma and Vasoactive Intestinal Polypeptide-Producing Tumor (VIPoma).

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar;42(2):348-52. doi: 10.1097/MPA.0b013e31825c53fa.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31825c53fa

AUTORES / AUTHORS:  - Bourcier ME; Vinik AI

INSTITUCIÓN / INSTITUTION:  - From the Strelitz Diabetes Center and Neuroendocrine Unit, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA.

RESUMEN / SUMMARY:  - OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (NETs) are rare tumors of the endocrine and nervous systems. Whereas early surgical resection can significantly reduce tumor mass, there are few data available concerning the control of hormonal secretion and associated symptoms. Studies have shown that the tyrosine kinase inhibitor sunitinib significantly prolongs progression-free survival in patients with pancreatic NETs. Here, we present 2 case reports of sunitinib in patients with different types of NETs. METHODS: The patients were a  12-year-old boy with metastatic vasoactive intestinal polypeptide-producing tumor (VIPoma) and a 70-year-old woman with metastatic paraganglioma/NET. Both were treated in an outpatient clinical setting. Sunitinib was titrated to 37.5 mg on a continuous daily dosing schedule in the patient with VIPoma, and the dose was 50  mg/d (4 weeks on, 2 weeks off) in the patient with the paraganglioma/NET. RESULTS: The patient with the paraganglioma/NET had a confirmed complete radiographic response and the patient with VIPoma had a confirmed partial response (Response Evaluation Criteria in Solid Tumors). In both patients, improvements were observed in biochemical tumor markers, clinical responses, and  quality of life. CONCLUSIONS: In these patients, sunitinib reduced biochemical markers and stabilized or reduced tumor bulk and may therefore be a potential therapeutic option for these tumor types.

 

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[113]

TÍTULO / TITLE:  - EpCAM-associated claudin-7 supports lymphatic spread and drug resistance in rat pancreatic cancer.

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

REVISTA / JOURNAL:  - Int J Cancer. 2013 Feb 6. doi: 10.1002/ijc.28085.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28085

AUTORES / AUTHORS:  - Thuma F; Zoller M

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

RESUMEN / SUMMARY:  - Pancreatic cancer has a dismal prognosis because of early metastatic spread, a suggested feature of cancer-initiating cells (CIC). To control for a functional contribution of the pancreatic CIC-marker EpCAM, we explored metastasis formation by a stable EpCAM-knockdown (ASML-EpCkd ) of the rat pancreatic adenocarcinoma line BSp73ASML (ASMLwt ). As EpCAM associates with claudin-7, an ASML-claudin-7-knockdown (ASML-cld7kd ) was included to differentiate between EpC- and EpC-cld7-mediated effects. The metastatic capacity of ASML-EpCkd and more pronounced ASML-cld7kd cells is strikingly reduced. EpC-associated cld7 interferes with EpC-mediated cell-cell adhesion and supports migration. This requires cld7 phosphorylation and formation of an EpC-cld7-tetraspanin-alpha6beta4 complex in glycolipid-enriched membrane domains  (GEM), where cld7 associates via the tetraspanin-alpha6beta4 complex with phosphorylated ezrin. The association of cld7 with alpha6beta4 and cytoskeleton strongly stimulates tumor cell migration. However, EpC does not actively contribute. Instead, GEM-located cld7 associates with presenilin-2, which facilitates EpC cleavage and thereby tumor cell proliferation. Finally, the EpC-cld7 complex promotes drug resistance. Both EpC and cld7 support MAPK and JNK activation, such that in ASML-EpCkd and ASML-cld7kd cells an undue expansion of proapoptotic molecules is observed. Only cld7 promotes activation of the PI3K/Akt pathway by a strong downregulation of Pten. Accordingly, cisplatin treatment prolongs the survival time of ASML-cld7kd -bearing rats. Taken together, cld7 supports tumorigenic features of EpC by provoking EpC cleavage and thereby its cotranscription factor activity. On the other hand, only cld7 is directly engaged in motility and apoptosis resistance. Thus, at least in concern of migrating CIC, it is cld7 that acts as a CIC biomarker.

 

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[114]

TÍTULO / TITLE:  - Mixed acinar-endocrine carcinoma of the pancreas: new clinical and pathological features in a contemporary series.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Apr;42(3):429-35. doi: 10.1097/MPA.0b013e318264d073.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318264d073

AUTORES / AUTHORS:  - Yu R; Jih L; Zhai J; Nissen NN; Colquhoun S; Wolin E; Dhall D

INSTITUCIÓN / INSTITUTION:  - From the *Division of Endocrinology,Departments of daggerPathology, double daggerSurgery, and section signDivision of Oncology, Cedars-Sinai Medical Center, Los Angeles, CA.

RESUMEN / SUMMARY:  - OBJECTIVE: The objective of this study was to characterize the novel clinical and pathological features of mixed acinar-endocrine carcinoma of the pancreas. METHODS: This was a retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of mixed acinar-endocrine carcinoma of the pancreas at Cedars-Sinai Medical Center between 2005 and 2011. Additional immunohistochemistry was performed on the specimens of some patients.  RESULTS: Five patients were identified. The median age at presentation was 74 years (range, 59-89 years), and all patients were male. The presenting symptoms were all related to tumor mass effects. The median size of the tumor was 10 cm (range, 3.9-16 cm). Preoperative clinical diagnosis aided by fine-needle aspiration biopsy was incorrect in all 5 cases. Most tumors (3/5) exhibited predominantly endocrine differentiation without hormonal production. Only 10% to  30% of cells were truly amphicrine, whereas most were differentiated into either  endocrine or acinar phenotype. The clinical behavior ranged from moderate to aggressive with postoperative survival from 2.5 months to more than 3 years. Four patients received neoadjuvant or adjuvant chemotherapy with variable responses. CONCLUSIONS: Mixed acinar-endocrine carcinoma of the pancreas appears to be not uncommon in men, may harbor predominantly endocrine component, is often misdiagnosed by cytology, and exhibits variable clinical behavior. Mixed acinar-endocrine carcinoma of the pancreas should be considered in older patients with sizable pancreatic mass and may warrant aggressive surgical resection and chemotherapy.

 

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[115]

TÍTULO / TITLE:  - Recurrent pancreatitis caused by pancreatic ductal villous adenoma treated with endoscopic snare polypectomy.

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

REVISTA / JOURNAL:  - Endoscopy. 2013;45 Suppl 2 UCTN:E23-4. doi: 10.1055/s-0032-1326108. Epub 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1326108

AUTORES / AUTHORS:  - Ramesh J; Council L; Wilcox CM

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. j1ramesh@gmail.com

 

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[116]

TÍTULO / TITLE:  - Inhibition of AKT in Human Pancreatic, Renal and Colorectal Cancer Cells by Four  Cardiac Hormones.

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Mar;33(3):785-90.

AUTORES / AUTHORS:  - Skelton WP 4th; Skelton M; Vesely DL

INSTITUCIÓN / INSTITUTION:  - Director, USF Cardiac Hormone Center, J.A. Haley Veterans Medical Center-151, 13000 Bruce B. Downs Blvd., Tampa, FL 33612, U.S.A. david.vesely@va.gov.

RESUMEN / SUMMARY:  - BACKGROUND: Protein kinase-B (AKT) is a serine/threonine protein kinase that has  a key role in cell proliferation and cancer cell invasiveness. Four cardiac peptide hormones, namely vessel dilator, atrial natriuretic peptide (ANP), kaliuretic peptide, and long-acting natriuretic peptide (LANP) have anticancer effects both in vitro and in vivo. MATERIALS AND METHODS: Four cardiac hormones were examined for their ability to inhibit AKT, measured with a solid-phase enzyme-linked immunosorbent assay (ELISA) in human colorectal, pancreatic, and renal cancer cells. RESULTS: Vessel dilator, kaliuretic peptide, ANP, and LANP maximally reduced the concentration of AKT by 47%, 45%, 52%, and 46% in human colorectal cancer cells (p<0.0001), by 60%, 61%, 64%, and 59% in human pancreatic carcinoma cells (p<0.0001), and by 31%, 32%, 31%, and 31% in renal adenocarcinoma cells (p<0.001). CONCLUSION: These four cardiac hormones are significant inhibitors of AKT in human cancer cells, as part of their anticancer mechanism(s) of action.

 

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[117]

TÍTULO / TITLE:  - PI3K/Akt/mTOR pathway inhibitors in the therapy of pancreatic neuroendocrine tumors.

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

REVISTA / JOURNAL:  - Cancer Lett. 2013 Feb 16. pii: S0304-3835(13)00128-6. doi: 10.1016/j.canlet.2013.02.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.016

AUTORES / AUTHORS:  - Wolin EM

INSTITUCIÓN / INSTITUTION:  - Division of Hematology/Oncology, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA. Electronic address: edward.wolin@cshs.org.

RESUMEN / SUMMARY:  - The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is implicated in the pathogenesis of pancreatic neuroendocrine tumors (pNETs). Activation of this pathway is driven by aberrant tyrosine kinase receptor activities. Mutations in the PI3K/Akt/mTOR pathway occur in 15% of pNETs, and expression of genes of the PI3K/Akt/mTOR pathway is altered in the majority of pNETs. The mTOR inhibitor everolimus has been approved by the FDA for the treatment of pNET, but its efficacy may be limited by its inability to prevent mTORC2-mediated activation of Akt. Specific inhibitors of PI3K, Akt, or other pathway nodes, and their concomitant use with mTOR inhibitors, or agents with dual activity, may be more effective. Preclinical studies demonstrate that inhibitors of the PI3K pathway have antitumor activity in pNET cells, either through direct inhibition of individual pathway nodes or indirect inhibition of molecular chaperones such as heat-shock protein 90. Clinical studies are underway evaluating individual node and dual node inhibitors.

 

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[118]

TÍTULO / TITLE:  - Differential ezrin and phosphorylated ezrin expression profiles between pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and invasive ductal carcinoma of the pancreas.

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

REVISTA / JOURNAL:  - Hum Pathol. 2013 Mar 1. pii: S0046-8177(12)00449-2. doi: 10.1016/j.humpath.2012.12.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.12.001

AUTORES / AUTHORS:  - Oda Y; Aishima S; Morimatsu K; Hayashi A; Shindo K; Fujino M; Mizuuchi Y; Hattori M; Tanaka M; Oda Y

INSTITUCIÓN / INSTITUTION:  - Department of Anatomic Pathology, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.

RESUMEN / SUMMARY:  - Intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanINs) are important premalignant lesions of pancreatic cancer. Ezrin is a member of the ezrin, radixin, and moesin protein family and acts as a cross-linker between the plasma membrane and the actin cytoskeleton. We investigated the roles of ezrin during carcinogenesis in IPMN and invasive ductal carcinoma and examined whether ezrin was a prognostic factor. We examined ezrin and phosphorylated ezrin (p-ezrin) expression in 131 IPMNs, 47 PanINs, and 59 invasive ductal carcinomas by immunohistochemical staining. Ezrin and p-ezrin (tyr354) expressions were significantly higher in IPMN with an associated invasive carcinoma, compared with those in IPMN with high-grade dysplasia (P = .03 and P = .0007, respectively). In all grades of PanINs, ezrin and p-ezrin (tyr353) were highly expressed. In patients with invasive ductal carcinoma, the presence of PanIN-2 or PanIN-3 was significantly correlated with positive ezrin and p-ezrin (tyr353) expression of the invasive ductal carcinoma component (P = .01 and P = .0004). The negative p-ezrin (tyr353) expression group of invasive ductal carcinoma showed a significantly worse prognosis than did the positive p-ezrin (tyr353) expression group by survival analysis (P = .04) and was a statistically significant adverse prognostic factor by both univariate and multivariate analyses (P = .048 and P = .015). Ezrin phosphorylation sites differ between the developments of IPMN and PanIN. Although p-ezrin (tyr354) expression  in IPMNs is associated with tumor invasion, p-ezrin (tyr353) expression in invasive ductal carcinoma plays an important role not in tumor invasion and metastasis but in the early development of PanINs.

 

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[119]

TÍTULO / TITLE:  - Proton therapy with concomitant capecitabine for pancreatic and ampullary cancers is associated with a low incidence of gastrointestinal toxicity.

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

REVISTA / JOURNAL:  - Acta Oncol. 2013 Apr;52(3):498-505. doi: 10.3109/0284186X.2012.762997.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2012.762997

AUTORES / AUTHORS:  - Nichols RC Jr; George TJ; Zaiden RA Jr; Awad ZT; Asbun HJ; Huh S; Ho MW; Mendenhall NP; Morris CG; Hoppe BS

INSTITUCIÓN / INSTITUTION:  - University of Florida Proton Therapy Institute , Jacksonville, Florida , USA.

RESUMEN / SUMMARY:  - Abstract Background. To review treatment toxicity for patients with pancreatic and ampullary cancer treated with proton therapy at our institution. Material and methods. From March 2009 through April 2012, 22 patients were treated with proton therapy and concomitant capecitabine (1000 mg PO twice daily) for resected (n = 5); marginally resectable (n = 5); and unresectable/inoperable (n = 12) biopsy-proven pancreatic and ampullary adenocarcinoma. Two patients with unresectable disease were excluded from the analysis for reasons unrelated to treatment. Proton doses ranged from 50.40 cobalt gray equivalent (CGE) to 59.40 CGE. Results. Median follow-up for all patients was 11 (range 5-36) months. No patient demonstrated any grade 3 toxicity during treatment or during the follow-up period. Grade 2 gastrointestinal toxicities occurred in three patients, consisting of vomiting (n = 3); and diarrhea (n = 2). Median weight loss during treatment was 1.3 kg (1.75% of body weight). Chemotherapy was well-tolerated with a median 99% of the prescribed doses delivered. Percentage weight loss was reduced (p = 0.0390) and grade 2 gastrointestinal toxicity was eliminated (p = 0.0009) in patients treated with plans that avoided anterior and left lateral fields which were associated with reduced small bowel and gastric exposure. Discussion. Proton therapy may allow for significant sparing of the small bowel and stomach and is associated with a low rate of gastrointestinal toxicity. Although long-term follow-up will be needed to assess efficacy, we believe that the favorable toxicity profile associated with proton therapy may allow for radiotherapy dose escalation, chemotherapy intensification, and possibly increased acceptance of preoperative radiotherapy for patients with resectable or marginally resectable disease.

 

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[120]

TÍTULO / TITLE:  - Evaluation of Clinical Meaning of Histological Subtypes of Intraductal Papillary  Mucinous Neoplasm of the Pancreas.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31827cddbc

AUTORES / AUTHORS:  - Kang MJ; Lee KB; Jang JY; Han IW; Kim SW

INSTITUCIÓN / INSTITUTION:  - From the *Department of Surgery and Cancer Research Institute and daggerDepartment of Pathology, Seoul National University College of Medicine, Seoul, South Korea.

RESUMEN / SUMMARY:  - OBJECTIVES: Prognostic value of histological subtypes of pancreatic intraductal papillary mucinous neoplasm (IPMN) has been reported to have conflicting results. The authors investigated the clinicopathological characteristics and prognostic significance of the histological subtypes of IPMNs with various degrees of dysplasia. METHODS: Two hundred thirteen patients with surgically treated pancreatic IPMN at a single tertiary care referral center were included. Pathological slides were thoroughly reviewed by a specialized pathologist. RESULTS: Of the 213 patients, 38 low-grade, 97 intermediate-grade, and 18 high-grade dysplasia and 59 IPMNs with an associated invasive carcinoma (invasive IPMN) were identified. Histological subtypes consisted of 135 gastric (63.4%), 38 intestinal (17.8%), 38 pancreatobiliary (17.8%), and 2 oncocytic types (0.9%). Histological subtypes were associated with radiological type (P < 0.001), degree  of dysplasia (P < 0.001), and T stage (P < 0.001). The proportions of invasive IPMN were 14.1%, 42.1%, 57.9%, and 100% of gastric, intestinal, pancreatobiliary, and oncocytic types, respectively. Disease-specific survival was not affected by  histological subtype in overall patients (P = 0.881). For invasive IPMNs, histological subtypes had a marginal significance on survival (P = 0.050), which  lost statistical significance after multivariate analysis (P = 0.341). CONCLUSIONS: Although histological subtypes are associated with the degree of dysplasia, histological subtypes have limited prognostic value for pancreatic IPMNs.

 

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[121]

TÍTULO / TITLE:  - Protein-bound polysaccharide decreases invasiveness and proliferation in pancreatic cancer by inhibition of hedgehog signaling and HIF-1alpha pathways under hypoxia.

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

REVISTA / JOURNAL:  - Cancer Lett. 2013 Feb 26. pii: S0304-3835(13)00167-5. doi: 10.1016/j.canlet.2013.02.041.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.041

AUTORES / AUTHORS:  - Onishi H; Morisaki T; Nakao F; Odate S; Morisaki T; Katano M

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: ohnishi@surg1.med.kyushu-u.ac.jp.

RESUMEN / SUMMARY:  - To develop an effective therapeutic approach to pancreatic ductal adenocarcinoma  (PDAC), we focused on the antitumor mechanism of protein-bound polysaccharide (PSK) under hypoxia. PSK decreased proliferation in PDAC cells under hypoxia but  not normoxia. PSK also showed anti-tumor effects in vivo, inhibited invasiveness  of PDAC cells, and decreased the expression of HIF-1alpha and hedgehog (Hh) signaling-related molecules under hypoxia. Inhibition of HIF-1alpha and Hh signaling reduced proliferation and invasiveness in PDAC cells under hypoxia. In  conclusion, we found new PSK-related pathways in invasiveness and proliferation in PDAC under hypoxia. PSK may be a promising therapeutic drug to treat refractory PDAC.

 

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[122]

TÍTULO / TITLE:  - MTA2 expression is a novel prognostic marker for pancreatic ductal adenocarcinoma.

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

REVISTA / JOURNAL:  - Tumour Biol. 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0685-3

AUTORES / AUTHORS:  - Chen DW; Fan YF; Li J; Jiang XX

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, The PLA 117 Hospital, No. 14, Lingyin Rd., Hangzhou, 310013, China.

RESUMEN / SUMMARY:  - The aim of this study was to detect MTA2 expression in pancreatic ductal adenocarcinoma (PDA) and to analyze its association with prognosis of PDA patients. MTA2 mRNA and protein expression were determined by real-time quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry in specimens of primary cancer and their adjacent noncancerous tissues in PDA patients. We found that MTA2 mRNA and protein expression levels were both significantly upregulated in PDA lesions compared with adjacent noncancerous tissues. Immunohistochemistry showed that high MTA2 expression was correlated with poor tumor differentiation, TNM stage, and lymph node metastasis. Kaplan-Meier survival analysis showed that patients with high expression levels of MTA2 showed lower overall survival rate than those with low  expression levels. Multivariate analysis showed that high MTA2 protein expression was an independent prognostic factor for PDA patients. Our study suggests that overexpression of MTA2 may play an important role in the progression of PDA and MTA2 expression may serve as a biomarker for poor prognosis for PDA.

 

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[123]

TÍTULO / TITLE:  - FDG PET/CT Detects Clinically Occult Pancreatic Cancer in a Case of Von Hippel-Lindau Syndrome.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31826c0de9

AUTORES / AUTHORS:  - Kulkarni M; Purandare N; Zade A; Agrawal A; Shah S; Rangarajan V

INSTITUCIÓN / INSTITUTION:  - From the Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Parel, Mumbai, India.

RESUMEN / SUMMARY:  - Von Hippel-Lindau (VHL) disease is a rare, inherited, multisystem disorder that is characterized by development of a variety of benign and malignant tumors. We report an incidental detection of clinically occult pancreatic malignancy on FDG  PET/CT in a patient of VHL who underwent restaging for a previously treated endolymphatic sac tumor.

 

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[124]

TÍTULO / TITLE:  - Metastatic Pancreatic Insulinoma with Treatment-limiting Thrombocytopenia.

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

REVISTA / JOURNAL:  - Am Surg. 2013 Mar;79(3):124-6.

AUTORES / AUTHORS:  - Nguyen AH; Donahue TR

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

 

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[125]

TÍTULO / TITLE:  - Novel role of VMP1 as modifier of the pancreatic tumor cell response to chemotherapeutic drugs.

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

REVISTA / JOURNAL:  - J Cell Physiol. 2013 Mar 4. doi: 10.1002/jcp.24343.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jcp.24343

AUTORES / AUTHORS:  - Gilabert M; Vaccaro MI; Fernandez-Zapico ME; Calvo EL; Turrini O; Secq V; Garcia S; Moutardier V; Lomberk G; Dusetti N; Urrutia R; Iovanna JL

INSTITUCIÓN / INSTITUTION:  - Cancer Research Center of Marseille, Inserm U1068; Institut Paoli-Calmettes; Aix-Marseille University; CNRS, UMR7258, F-13288, Marseille, France.

RESUMEN / SUMMARY:  - We hypothesized that inhibiting molecules that mediate the adaptation response to cellular stress can antagonize the resistance of pancreatic cancer cells to chemotherapeutic drugs. Toward this end, here, we investigated how VMP1, a stress-induced autophagy-associated protein, modulate stress responses triggered  by chemotherapeutic agents in PDAC. We find that VMP1 is particularly over-expressed in poorly differentiated human pancreatic cancer. Pharmacological  studies show that drugs that work, in part, via the endoplasmic reticulum stress  response, induce VMP1 expression. Similarly, VMP1 is induced by known endoplasmic reticulum stress activators. Genetic inactivation of VMP1 using RNAi-based antagonize the pancreatic cancer stress response to antitumoral agents. Functionally, we find that VMP1 regulates both autophagy and chemotherapeutic resistance even in the presence of chloroquin, ATG5 or Beclin 1 siRNAs, or a Beclin 1-binding VMP1 mutant. In addition, VMP1 modulates endoplasmic reticulum stress independently of its coupling to the molecular and cellular autophagy machinery. Preclinical studies demonstrate that xenografts expressing an inducible and tractable form of VMP1 show increased resistance to the gemcitabine treatment. These results underscore a novel role for VMP1 as a potential therapeutic target for combinatorial therapies aimed at sensitizing pancreatic cancer cells to chemotherapeutic agents as well as provide novel molecular mechanisms to better understand this phenomenon. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.

 

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[126]

TÍTULO / TITLE:  - Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells.

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

REVISTA / JOURNAL:  - World J Gastroenterol. 2013 Mar 14;19(10):1582-92. doi: 10.3748/wjg.v19.i10.1582.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i10.1582

AUTORES / AUTHORS:  - Tang XP; Tang GD; Fang CY; Liang ZH; Zhang LY

INSTITUCIÓN / INSTITUTION:  - Xi-Ping Tang, Guo-Du Tang, Chun-Yun Fang, Zhi-Hai Liang, Lu-Yi Zhang, Department  of Gastroenterology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.

RESUMEN / SUMMARY:  - AIM: To investigate the effects of ginsenoside Rh2 on the human pancreatic cancer cell line Bxpc-3. METHODS: The human pancreatic cancer cell line Bxpc-3 was cultured in vitro and treated with or without ginsenoside Rh2. Growth rates for Bxpc-3 cells were assessed by methyl thiazolyl tetrazolium (MTT) and colony formation assays. Cell cycle changes were analyzed by flow cytometry. Apoptosis was measured by flow cytometry and Hoechst 33258 fluorescence staining. A scratch assay and a Matrigel invasion assay were used to detect cell migration and invasion. Expression of Bax, Bcl-2, survivin, cyclin D1, matrix metalloproteinase (MMP)-2, MMP-9, cleaved caspase-3, caspase-8, and caspase-9 mRNA were determined  by reverse transcriptase-polymerase chain reaction (RT-PCR). Bax, Bcl-2, survivin, cyclin D1, cleaved caspase-3, caspase-8 and caspase-9 protein levels were examined by western blotting. Expression of MMP-2 and MMP-9 proteins in culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Rh2 significantly inhibited Bxpc-3 cell proliferation in a dose- and time-dependent manner, as evaluated by the MTT (P < 0.05) and colony formation assays (P < 0.05). Compared to the control group, Rh2 significantly increased the percentage of Bxpc-3 cells in the G0/G1 phase from 43.32% +/- 2.17% to 71.32% +/- 1.16%, which was accompanied by a decrease in S phase (from 50.86%  +/- 1.29% to 28.48% +/- 1.18%) and G2/M phase (from 5.81% +/- 1.19% to 0.20% +/-  0.05%) in a dose-dependent manner (P < 0.05), suggesting that Rh2 arrested cell cycle progression at the G0/G1 phase, as measured by flow cytometry. Compared to  the control group, cells treated with Rh2 showed significantly higher apoptosis ratios in a dose-dependent manner (percentage of early apoptotic cells: from 5.29% +/- 2.28% to 38.90% +/- 3.42% (F = 56.20, P < 0.05); percentage of late apoptotic cells: from 4.58% +/- 1.42% to 36.32% +/- 2.73% (F = 86.70, P < 0.05).  Rh2 inhibited Bxpc-3 cell migration and invasion, as detected by scratch wound healing assay and Matrigel invasion assay [percentages of scratch wound healing for 12 h, 24 h and 48 h (control vs experimental group): 37.3% +/- 4.8% vs 18.30% +/- 1.65%, 58.7% +/- 3.5% vs 38.00% +/- 4.09% and 93.83% +/- 4.65% vs 65.50% +/-  4.09%, respectively; t = 6.489, t = 6.656 and t = 7.926, respectively, P < 0.05;  the number of cells invading at various concentrations (0 mumol/L, 35 mumol/L, 45 mumol/L and 55 mumol/L): 81.10 +/- 9.55, 46.40 +/- 6.95, 24.70 +/- 6.88 and 8.70  +/- 3.34, respectively (F = 502.713, P < 0.05)]. RT-PCR, western blotting or ELISA showed that mRNA and protein expression of Bax, cleaved caspase-3 and caspase-9 were upregulated (P < 0.05), while mRNA and protein expression of Bcl-2, survivin, cyclin D1, MMP-2 and MMP-9 were downregulated (P < 0.05). CONCLUSION: Ginsenoside Rh2 inhibits proliferation, migration and invasion and induces apoptosis of the human pancreatic cancer cell line Bxpc-3.

 

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[127]

TÍTULO / TITLE:  - CacyBP/SIP enhances multidrug resistance of pancreatic cancer cells by regulation of P-gp and Bcl-2.

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

REVISTA / JOURNAL:  - Apoptosis. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0831-9

AUTORES / AUTHORS:  - Chen X; Zheng P; Xue Z; Li J; Wang W; Chen X; Xie F; Yu Z; Ouyang X

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian, China, cxzpc81@gmail.com.

RESUMEN / SUMMARY:  - Our former report indicates that calcyclin-binding protein or Siah-1-interacting  protein (CacyBP/SIP) is over-expressed in the SGC7901/ADR cell line. However, the potential role of CacyBP/SIP in the development of multidrug resistance (MDR) of  pancreatic cancer is still uncertain. In this paper, we investigated the role of  CacyBP/SIP in MDR of pancreatic cancer cells and its possible underlying mechanisms, and found that CacyBP/SIP was over-expressed in the Gemcitabine induced MDR pancreatic cancer cell PC-3/Gem compared with its parental cell PC-3. Up-regulation of CacyBP/SIP expression could enhance resistance of chemotherapy drugs on PC-3 cells and inhibit Adriamycin-induced apoptosis accompanied by decreased accumulation of intracellular Adriamycin. Furthermore, CacyBP/SIP could significantly up-regulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene. In addition, the decrease of CacyBP/SIP expression using RNA interference or P-gp inhibitor could partially reverse CacyBP/SIP-mediated MDR. In brief, our study demonstrated that CacyBP/SIP could enhance the MDR phenotype  of pancreatic cancer cells by increasing the expression of P-gp and Bcl-2, thus inhibiting apoptosis of pancreatic cancer cell.

 

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[128]

TÍTULO / TITLE:  - Distinct claudin expression profiles of hepatocellular carcinoma and metastatic colorectal and pancreatic carcinomas.

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

REVISTA / JOURNAL:  - J Histochem Cytochem. 2013 Apr;61(4):294-305. doi: 10.1369/0022155413479123. Epub 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1369/0022155413479123

AUTORES / AUTHORS:  - Holczbauer A; Gyongyosi B; Lotz G; Szijarto A; Kupcsulik P; Schaff Z; Kiss A

INSTITUCIÓN / INSTITUTION:  - 2nd Department of Pathology (AH,BG,GL,ZS,AK), Semmelweis University, Budapest, Hungary.

RESUMEN / SUMMARY:  - Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin  expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 colorectal adenocarcinomas (CRLMs) and 15 pancreatic adenocarcinomas (PLMs) were studied together with paired surrounding non-tumorous liver samples and 5 normal liver samples. Strong claudin-3 and -7 immunohistochemical positivities were detected in CRLM samples, each with significantly stronger staining when compared with HCC and PLM groups. Claudin-1  protein was found highly expressed in CRLM, in contrast to lower expression in PLM and HCC. CRLMs and PLMs also were strongly positive for claudin-4, while being virtually undetectable in HCC. Claudin-2 showed strong positivity in non-tumorous liver tissue, whereas significantly weaker positivity was observed in all tumors. Differences in mRNA expression were mostly similar to those found  by immunohistochemistry. In conclusion, HCC and both CRLM and PLM display distinct claudin expression profiles, which might provide better understanding of the pathobiology of these lesions and might be used for differential diagnosis.

 

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[129]

TÍTULO / TITLE:  - Systemic therapy for advanced pancreatic neuroendocrine tumors.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):75-83. doi: 10.1053/j.seminoncol.2012.11.010.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.010

AUTORES / AUTHORS:  - Kulke MH

INSTITUCIÓN / INSTITUTION:  - Program in Neuroendocrine and Carcinoid Tumors, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USA. Matthew_Kulke@dfci.harvard.edu

RESUMEN / SUMMARY:  - Neuroendocrine tumors (NETs) occur throughout the body, and share similar histologic characteristics. However, it has become increasingly evident that pancreatic NETs tend to respond differently to therapeutic agents than do other NET subtypes. In most cases, systemic therapy has been more effective in NETs of  pancreatic origin than in NETs arising from other locations. Traditional systemic treatment options for pancreatic NETs include somatostatin analogs or cytotoxic chemotherapy. Recently, the biologically targeted agents everolimus and sunitinib were approved for use in patients with metastatic disease. Novel agents, as well  as novel drug combinations, are currently under investigation.

 

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[130]

TÍTULO / TITLE:  - Follow-up after curative surgery for pancreatic ductal adenocarcinoma: Asymptomatic recurrence is associated with improved survival.

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

REVISTA / JOURNAL:  - Eur J Surg Oncol. 2013 Mar 13. pii: S0748-7983(13)00265-5. doi: 10.1016/j.ejso.2013.02.020.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejso.2013.02.020

AUTORES / AUTHORS:  - Nordby T; Hugenschmidt H; Fagerland MW; Ikdahl T; Buanes T; Labori KJ

INSTITUCIÓN / INSTITUTION:  - Department for Hepato-Pancreato-Biliary Surgery, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Sognsvannsveien 20, N-0027 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of  Oslo, Norway.

RESUMEN / SUMMARY:  - AIM: There is no consensus on the optimal follow-up schedule of patients after surgery for pancreatic cancer. In this retrospective study, recurrence and survival were investigated for patients presenting with either symptomatic or asymptomatic recurrence. Patient, tumor and treatment characteristics that predicted the length of postrecurrence survival were identified. METHODS: Clinical records of 164 patients who underwent a pancreatic resection (R0/R1) for pancreatic ductal adenocarcinoma from January 2000 to December 2010 were retrieved. Patients underwent a systematic follow-up program. Patient, tumor and  treatment characteristics were compared between patients with asymptomatic and symptomatic recurrence. RESULTS: Of 164 consecutive patients, 144 patients (88%)  had recurrence (29 asymptomatic, 115 symptomatic). The most frequent reported symptoms were abdominal pain, fatigue/weakness, back pain, weight loss, nausea/loss of appetite and jaundice. Median time to recurrence was 12.0 months for asymptomatic and 7.0 months for symptomatic patients (P = 0.036). Median postrecurrence survival was 10.0 months for asymptomatic and 4.0 months for symptomatic patients (P < 0.0001). Median overall survival was 24.5 months for asymptomatic and 11.0 months for symptomatic patients (P < 0.0001). Symptomatic recurrence, disease free survival <12 months, and no adjuvant chemotherapy were the only independent predictors of poor postrecurrence survival. 72% of asymptomatic and 37% of symptomatic patients received oncological treatment. CONCLUSIONS: Patients with asymptomatic pancreatic cancer recurrence have improved recurrence-free, postrecurrence and overall survival. Symptoms when recurrence is diagnosed are a good surrogate marker of biological aggressiveness. Detection of asymptomatic recurrence may facilitate patient eligibility for investigational studies or other forms of treatment.

 

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[131]

TÍTULO / TITLE:  - Kindlin-2 Expression in Peritumoral Stroma Is Associated With Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279bd66

AUTORES / AUTHORS:  - Mahawithitwong P; Ohuchida K; Ikenaga N; Fujita H; Zhao M; Kozono S; Shindo K; Ohtsuka T; Mizumoto K; Tanaka M

INSTITUCIÓN / INSTITUTION:  - From the *Departments of Surgery and Oncology, and daggerAnatomic Pathology, Kyushu University, Fukuoka, Japan.

RESUMEN / SUMMARY:  - OBJECTIVES: Kindlin-2 is a novel focal adhesion protein reported to be expressed  in breast, lung, and gastric cancers. This study aimed to investigate the significance of kindlin-2 expression in pancreatic ductal adenocarcinomas (PDACs). METHODS: We performed immunohistochemical analysis on kindlin-2 on PDAC  samples from 95 patients. We investigated the association between kindlin-2 expression and clinicopathological parameters of PDAC and the survival time of patients with PDAC who underwent pancreatectomy. RESULTS: Kindlin-2 was highly expressed in the peritumoral stroma of PDACs. Stromal kindlin-2 expression was related to nodal metastasis (P = 0.03). Univariate analysis showed that patients  with positive kindlin-2 expression had significantly shorter survival times than  those with negative kindlin-2 expression (P = 0.01). In addition, multivariate analysis revealed that kindlin-2 expression was an independent factor of poor prognosis in patients with PDAC after R0 resection (RR = 2.15; P = 0.04). CONCLUSIONS: Kindlin-2 expression in stromal components is significantly associated with poor prognosis of patients with PDAC, suggesting that kindlin-2 is a prognostic marker for patients with PDAC.

 

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[132]

TÍTULO / TITLE:  - Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Mar 5;108(4):914-23. doi: 10.1038/bjc.2013.32. Epub 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.32

AUTORES / AUTHORS:  - Ino Y; Yamazaki-Itoh R; Shimada K; Iwasaki M; Kosuge T; Kanai Y; Hiraoka N

INSTITUCIÓN / INSTITUTION:  - Division of Molecular Pathology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

RESUMEN / SUMMARY:  - Background:The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact.Methods:Using immunohistochemistry, we examined  tumour-infiltrating CD68 pan-macrophages, HLA-DRCD68 M1 macrophages (M1), CD163 or CD204 M2 macrophages (M2), CD66b neutrophils (Neu), CD4 T cells (CD4T), CD8 T  cells (CD8T), and FOXP3CD4 regulatory T cells (Treg) in 212 cases of PDC, and conducted correlation and survival analyses using the Kaplan-Meier method and Cox proportional hazards model.Results:Higher levels of tumour-infiltrating pan-macrophages, M2, Neu, or the ratio of Tregs to CD4T (%Treg) were significantly associated with shorter survival, whereas higher levels of tumour-infiltrating CD4T, CD8T, or the ratio of M1 to pan-macrophages (%M1) were  significantly associated with longer survival. Survival analysis of pairs of these variables revealed that some of the resulting patient groups had exclusively longer survival. We then connected the apparently related factors, and two significant variables emerged: tumour-infiltrating CD4T/CD8T/%Treg and tumour-infiltrating %M1/M2. Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio.Conclusion:Tumour-infiltrating CD4T/CD8T/%Treg and %M1/M2 are independent prognosticators useful for evaluating the immune microenvironment of  PDC.

 

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[133]

TÍTULO / TITLE:  - Molecular biology of adenocarcinoma of the pancreatic duct, current state and future therapeutic avenues.

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

REVISTA / JOURNAL:  - Surg Oncol. 2013 Feb 15. pii: S0960-7404(12)00092-8. doi: 10.1016/j.suronc.2012.12.002.

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

AUTORES / AUTHORS:  - Abbas S

INSTITUCIÓN / INSTITUTION:  - Deakin University, Barwon Health, Bellerine St, Geelong 3200, Vic, Australia. Electronic address: salehabbas@yahoo.com.

RESUMEN / SUMMARY:  - Pancreatic adenocarcinoma is a lethal disease; currently surgery offers five years survival of less than 5%. Any improvement in the outcome is likely to be through novel therapeutic agents that will target the genetic machinery of the cell. Knowledge of genetic alterations in the process of carcinogenesis is expanding rapidly, the targeted therapy, however, is progressing slowly. Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lend the cancer cells their ability not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes involve genetic alteration in oncogenes, cancer suppressor genes, changes in cell cycle, pathways of apoptosis and also changes in epithelial to mesenchymal transition. Monotherapeutic targeted agents seem(s) to  have limited effect on cancer cells. The near future is likely to show an improvement in the treatment outcome, which is likely to be a result of the combination of targeted agents with surgery and chemotherapy.

 

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[134]

TÍTULO / TITLE:  - Controversial issues of neoadjuvant treatment in borderline resectable pancreatic cancer.

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

REVISTA / JOURNAL:  - Surg Oncol. 2013 Mar 18. pii: S0960-7404(13)00025-X. doi: 10.1016/j.suronc.2013.02.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.suronc.2013.02.007

AUTORES / AUTHORS:  - Kang CM; Hwang HK; Choi SH; Lee WJ

INSTITUCIÓN / INSTITUTION:  - 50 Yonsei-ro, Seodaemun-gu, Department of Surgery, Yonsei University College of Medicine, Pancreaticobiliary Cancer Clinic, Institute of Gastroenterology, Severance Hospital, Seoul 120752, Republic of Korea.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma is known as one of the most fatal malignant diseases in gastrointestinal system. Approximately 20% of patients are deemed resectable at the time of diagnosis. Preoperative neoadjuvant therapy to the borderline resectable pancreatic cancer (BRPC) has been challenged to achieve down-staging of cancer, to avoid unnecessary major operation if the pancreatic cancer progresses and distant metastasis develops during preoperative treatment,  and to avoid delayed adjuvant treatment after major operation due to postoperative complications and poor general condition after major surgery. However, there are some controversial issues influencing the clinical interpretation of surgical and oncologic outcomes of pancreatectomy following neoadjuvant treatment in managing BRPC. This manuscript reviews the current controversial issues in managing BRPC in order to enhance proper understanding the current status and potential role of neoadjuvant treatment in managing BRPC.

 

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[135]

TÍTULO / TITLE:  - Kindlin-1 expression is involved in migration and invasion of pancreatic cancer.

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

REVISTA / JOURNAL:  - Int J Oncol. 2013 Apr;42(4):1360-6. doi: 10.3892/ijo.2013.1838. Epub 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1838

AUTORES / AUTHORS:  - Mahawithitwong P; Ohuchida K; Ikenaga N; Fujita H; Zhao M; Kozono S; Shindo K; Ohtsuka T; Aishima S; Mizumoto K; Tanaka M

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

RESUMEN / SUMMARY:  - Kindlin-1 is a novel focal adhesion protein that belongs to the kindlin family. Expression of kindlin-1 has recently been reported in lung and colon cancers, but there have been no studies on its expression in pancreatic cancer. This study aimed to investigate the expression and function of kindlin-1 in pancreatic cancer. Quantitative RT-PCR of Kindlin-1 mRNA was performed in various pancreatic cancer cell lines as well as normal pancreatic epithelial cells and fibroblasts.  Immunohistochemical analysis of kindlin-1 was performed for pancreatic cancer tissues. The effects of kindlin-1 on the proliferation, migration and invasion of pancreatic cancer cells were investigated using an RNA interference technique. Kindlin-1 mRNA was highly expressed in the pancreatic cancer cell lines, but only slightly expressed in normal pancreatic epithelial cells and fibroblasts. The Kindlin-1 protein was heterogeneously expressed in the cytoplasm and membrane of  pancreatic cancer cells, while normal ductal epithelial cells and stromal cells showed no expression. In vitro experiments involving knockdown of kindlin-1 in AsPC-1 and KP-2 cells revealed that the migratory and invasive abilities of the cells were significantly decreased (P<0.001), while the proliferation abilities were not affected. The present findings suggest that kindlin-1 expression is involved in the progression of pancreatic cancer via enhancement of cell migration and invasion.

 

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[136]

TÍTULO / TITLE:  - Delayed Small Bowel Transit in Children with Cystic Fibrosis and Pancreatic Insufficiency.

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

REVISTA / JOURNAL:  - J Pediatr Gastroenterol Nutr. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPG.0b013e318290d112

AUTORES / AUTHORS:  - Rovner AJ; Schall JI; Mondick JT; Zhuang H; Mascarenhas MR

INSTITUCIÓN / INSTITUTION:  - *Division of Gastroenterology, Hepatology and Nutrition daggerDepartment of Radiology double daggerThe Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Metrum Institute, Tariffville, CT.

RESUMEN / SUMMARY:  - OBJECTIVE:: Gastrointestinal (GI) disturbances are common in people with cystic fibrosis (CF); however, motility studies in this population have yielded inconsistent results.This study examined gastric emptying (GE) and small bowel transit (SBT) time in children with CF and pancreatic insufficiency (PI) compared to a healthy adult reference group. METHODS:: Participants consumed an 8-ounce liquid test meal (approximately 550 calories, 32 grams of fat) labeled with 300 uCi 99m Technetium (Tc) sulfur colloid. Subjects with CF received a standard dose of pancreatic enzymes prior to consuming the test meal. GE and SBT were measured  using a standard nuclear medicine scan. GE was determined after correcting for 99mTc decay in both anterior and posterior images. SBT was determined by following the movement of the tracer from the stomach to the cecum. The percent arrival of total small bowel activity at the terminal ileum and cecum/ascending colon at 6 hours was used as an index of SBT. A one way analysis of covariance (ANCOVA) was performed for comparisons between groups after adjustment forage, gender and BMI. RESULTS:: Subjects with CF (n = 16) had similar GE compared to the healthy reference group (n = 12). However, subjects with CF had significantly prolonged SBT time. At 6 hours 37.2 +/- 25.4% (95%CI: 23.7, 50.7) of the tracer reached the terminal ileum and colon compared to 68.6 +/- 13.1% (95%CI: 60.2, 76.9) for the reference group (p < 0.001). After controlling forgender, age and BMI this difference remained statistically significant (F = 12.06, adjusted R = 0.44, p < 0.002). CONCLUSIONS:: Children with CF and PI had unaltered GE but delayed SBT time when taking pancreatic enzymes.

 

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[137]

TÍTULO / TITLE:  - A potential window onto early pancreatic cancer development: evidence of cancer stem cell growth after exposure to cadmium chloride in vitro.

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

REVISTA / JOURNAL:  - Environ Health Perspect. 2012 Sep;120(9):A363.

AUTORES / AUTHORS:  - Barrett JR

 

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[138]

TÍTULO / TITLE:  - Vascular proliferation is associated with survival in pancreatic ductal adenocarcinoma.

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

REVISTA / JOURNAL:  - APMIS. 2013 Mar 13. doi: 10.1111/apm.12057.

            ●● Enlace al texto completo (gratuito o de pago) 1111/apm.12057

AUTORES / AUTHORS:  - Hoem D; Straume O; Immervoll H; Akslen LA; Molven A

INSTITUCIÓN / INSTITUTION:  - Department of Gastrointestinal Surgery, Haukeland University Hospital, Bergen, Norway.

RESUMEN / SUMMARY:  - In pancreatic ductal adenocarcinoma (PDAC), the benefit of current chemotherapy and radiation therapy is very limited, even in radically resected patients. New treatment strategies, for example based on the inhibition of the tumour’s blood supply, need to be explored. We have investigated angiogenesis markers and their  associations with relapse and survival in 52 histologically confirmed cases of PDAC. Angiogenesis in the primary tumour was evaluated by microvessel density (MVD), vascular proliferation index (VPI) and the presence of glomeruloid microvascular proliferations (GMP). These features were analysed in the context of clinicopathological variables, KRAS mutation status, relapse location and survival. MVD (median 134 microvessels/mm2 , range 88-177) and VPI (median 3.2%,  range 1.6-4.9) were associated with larger tumour size and lymph node metastasis. MVD was also related to the occurrence of liver metastases. Both variables were associated with survival in univariate and multivariate analyses. GMPs were present in 32 (62%) of the cases. Patients who exhibited MVD and VPI values above median, and GMP positivity, had a median survival of only 4.2 months after surgery. In conclusion, the angiogenesis markers MVD and VPI have a significant impact on survival. By also including GMP, a subgroup of PDAC patients with particularly short survival could be identified.

 

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[139]

TÍTULO / TITLE:  - Preoperative evaluation of the cystic duct for laparoscopic cholecystectomy: comparison of navigator-gated prospective acquisition correction- and conventional respiratory-triggered techniques at free-breathing 3D MR cholangiopancreatography.

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

REVISTA / JOURNAL:  - Eur Radiol. 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00330-013-2790-5

AUTORES / AUTHORS:  - Itatani R; Namimoto T; Kajihara H; Yoshimura A; Katahira K; Nasu J; Matsushita I; Sakamoto F; Kidoh M; Yamashita Y

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Kumamoto Chuo Hospital, 1-5-1, Tainoshima, Kumamoto, 862-0965, Japan.

RESUMEN / SUMMARY:  - OBJECTIVE: To evaluate the quality of magnetic resonance cholangiopancreatography (MRCP) images obtained with a three-dimensional navigator-gated (NG) technique and compare findings with conventional respiratory-triggered (RT) images in pre-laparoscopic cholecystectomy patients. METHODS: Turbo-spin-echo (TSE) RT-MRCP (average 242 s) and balanced turbo-field-echo (bTFE) NG-MRCP (average 263 s) were acquired at 1.5-T MRI for 49 pre-laparoscopic cholecystectomy patients. Two radiologists independently assessed image quality, visibility of anatomical structures, common bile duct (CBD) stones, and signal-to-noise ratios (SNRs). Interobserver agreement was also evaluated. RESULTS: The anatomical details of the cystic duct were clearly demonstrated in 33 (67.3 %, reader A) and 35 (71.4 %, reader B) patients on RT-MRCP, and in 45 (91.8 %) and 44 (89.7 %) patients on  NG-MRCP. On NG-MRCP, visualisation of the cystic duct (3.22/3.12), its origin (3.57/3.55), and the gallbladder(3.61/3.59) was statistically better than on RT-MRCP (2.90/2.78, 3.29/3.12, 2.98/2.88, respectively). The overall image quality was statistically better on NG-MRCP than RT-MRCP. Each technique identified the presence of CBD stones in all affected patients. The SNR was significantly higher on NG-MRCP (CHD 22.40, gallbladder 17.13) than RT-MRCP (CHD  17.05, gallbladder 9.30). Interobserver agreement was fair to perfect. CONCLUSION: Navigator-gated MRCP is more useful than respiratory-triggered MRCP for evaluating the gallbladder and cystic duct in patients scheduled for laparoscopic cholecystectomy. KEY POINTS : * Magnetic resonance cholangiopancreatography (MRCP) provides important cystic duct information before laparoscopic cholecystectomy. * Navigator-gated (NG) MRCP images were better than conventional respiratory-triggered (RT) MRCP. * The signal-to-noise ratio was significantly higher for NG-MRCP than for conventional RT-MRCP. * Balanced turbo-field-echo NG-MRCP is useful for evaluating the gallbladder and cystic duct.

 

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[140]

TÍTULO / TITLE:  - Serum osteopontin and tissue inhibitor of metalloproteinase 1 as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar;42(2):193-7. doi: 10.1097/MPA.0b013e31825e354d.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31825e354d

AUTORES / AUTHORS:  - Poruk KE; Firpo MA; Scaife CL; Adler DG; Emerson LL; Boucher KM; Mulvihill SJ

INSTITUCIÓN / INSTITUTION:  - From the *Department of Surgery, daggerHuntsman Cancer Institute, double daggerDivision of Gastroenterology and Hepatology, Department of Internal Medicine, section signDepartment of Pathology, and parallelDepartment of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT.

RESUMEN / SUMMARY:  - OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival  rate of 5%. There is an urgent need for early detection while the tumors are small and surgically resectable. We assessed serum osteopontin (OPN) and tissue inhibitor of metalloproteinase 1 (TIMP-1) as possible diagnostic and prognostic biomarkers in a novel cohort of patients with pancreatic cancer. METHODS: Osteopontin and TIMP-1 levels were determined in sera from 86 patients with PDAC, 86 healthy control subjects, and 48 patients with chronic pancreatitis. Regression models were used to relate OPN and TIMP-1 to sex, age, stage, class, and treatment. Survival analyses were performed using univariate and multivariate Cox models. RESULTS: The serum levels of both OPN and TIMP-1 distinguished PDAC from chronic pancreatitis (P </= 0.0001) and healthy control subjects (P < 0.0001). The serum levels of both OPN and TIMP-1 also distinguished early-stage resectable PDAC cases from chronic pancreatitis (P < 0.04) and healthy control subjects (P < 0.01). High serum levels of OPN were significantly correlated with  reduced patient survival. CONCLUSIONS: Serum OPN and TIMP-1 have use as diagnostic biomarkers in PDAC. Our data suggest a potential benefit of using OPN, TIMP-1, and CA 19-9 in a panel to improve diagnostic accuracy in PDAC.

 

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[141]

TÍTULO / TITLE:  - Spontaneous rupture of solid pseudopapillary neoplasm of the pancreas during pregnancy.

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

REVISTA / JOURNAL:  - Obstet Gynecol. 2013 Feb;121(2 Pt 2 Suppl 1):486-8. doi: 10.1097/AOG.0b013e31826d292f.

AUTORES / AUTHORS:  - Huang SC; Wu TH; Chen CC; Chen TC

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Taoyuan, Taiwan.

RESUMEN / SUMMARY:  - BACKGROUND: Spontaneous rupture of solid pseudopapillary neoplasm of the pancreas is an unusual complication during pregnancy. CASE: At 19 weeks of gestation, a 29-year-old woman presented with a pancreatic mass and upper abdominal pain radiating to the back. On the third day of admission, shock and peritoneal signs  developed. Exploratory laparotomy and subsequent subtotal pancreatectomy were performed for a bleeding tumor. Solid pseudopapillary neoplasm was confirmed by pathological examination. The patient delivered a healthy full-term girl vaginally. Eight months postoperatively, the clinical courses of both mother and  infant have been uneventful. CONCLUSION: Ruptured solid pseudopapillary neoplasms can cause an acute abdomen during pregnancy. The expression of progesterone receptors in solid pseudopapillary neoplasm is a possible cause of this potentially devastating event.

 

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[142]

TÍTULO / TITLE:  - Synergistic interactions between sorafenib and everolimus in pancreatic cancer xenografts in mice.

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

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Mar 3.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2117-x

AUTORES / AUTHORS:  - Pawaskar DK; Straubinger RM; Fetterly GJ; Hylander BH; Repasky EA; Ma WW; Jusko WJ

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA.

RESUMEN / SUMMARY:  - PURPOSE: Molecular targeting of cellular signaling pathways is a promising approach in cancer therapy, but often fails to achieve sustained benefit because  of the activation of collateral cancer cell survival and proliferation pathways.  We tested the hypothesis that a combination of targeted agents that inhibit compensatory pathways would be more effective than single agents in controlling pancreatic cancer cell growth. We investigated whether everolimus, an mTOR inhibitor, and sorafenib, a multi-kinase inhibitor, would together inhibit growth of low-passage, patient-derived pancreatic cancer xenografts in mice more efficaciously than either agent alone. METHODS: Tumor volume progression was measured following treatment with both drugs as single agents, in combination, and at multiple doses. Pharmacokinetics in tumors and other tissues was also assessed. Pharmacodynamic interactions were evaluated quantitatively. RESULTS: A  5-week regimen of daily oral doses of 10 mg/kg sorafenib and 0.5 mg/kg everolimus, alone and in combination, did not achieve significant tumor growth inhibition. Higher doses (20 mg/kg of sorafenib and 1 mg/kg of everolimus) inhibited tumor growth significantly when given alone and caused complete inhibition of growth when given in combination. Tumor volume progression was described by a linear growth model, and drug effects were described by Hill-type  inhibition. Using population modeling approaches, dual-interaction parameter estimates indicated a highly synergistic pharmacodynamic interaction between the  two drugs. CONCLUSIONS: The results indicate that combinations of mTOR and multi-kinase inhibitors may offer greater efficacy in pancreatic cancer than either drug alone. Drug effects upon tumor stromal elements may contribute to the enhanced anti-tumor efficacy.

 

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[143]

TÍTULO / TITLE:  - The effect of gadolinium chelate contrast agent on diffusion-weighted imaging of  pancreatic ductal adenocarcinoma.

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

REVISTA / JOURNAL:  - Acta Radiol. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0284185112471795

AUTORES / AUTHORS:  - Liu K

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Fudan University Shanghai Cancer Center.

RESUMEN / SUMMARY:  - Background:There are only two studies that discuss the effect of a gadolinium chelate contrast agent on pancreatic diffusion-weighted imaging (DWI). However, both studies only included normal pancreas and/or pancreas with pancreatitis and  did not include pancreatic ductal adenocarcinoma (PDA). Purpose: To investigate the effect of gadolinium chelate contrast agent on DWI of PDA.Material and Methods:Twenty-two patients (13 men, 9 women; mean age 62 years) with histopathologically proven PDA were included in this study. DWI was acquired before and after administration of gadopentetate dimeglumine (Magnevist) with two b-values: 0 and 1000 s/mm2. The signal intensity (SI), signal-to-noise ratio (SNR), and the apparent diffusion coefficient (ADC) of the lesion were recorded for comparison.Results:The mean time interval between the initiation of contrast  administration and the start of the postcontrast DWI series was 393 s (range, 350-510 s). The SIs and SNRs of lesions of b1000 and b0 images of enhanced images were significantly higher than non-enhanced images (P, 0.001, P, 0.001 for b1000  s/mm2; P &frac14; 0.001, P &frac14; 0.001 for b0 s/mm2). The ADC of all PDAs revealed no statistically significant difference between non-enhanced and enhanced images (P &frac14; 0.709). There was also no significant difference between non-enhanced and enhanced images in subgroups based on grades of differentiation and locations of lesion.Conclusion: With increasing SI and SNR of PDA, intravenous contrast administration does not result in a significant difference in quantitative ADC measurements when comparing precontrast to postcontrast DWI when acquired approximately 6-7 min after administration.

 

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[144]

TÍTULO / TITLE:  - CA 19-9 Nonproduction Is Associated With Poor Survival After Resection of Pancreatic Adenocarcinoma.

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

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e318280d5f0

AUTORES / AUTHORS:  - Hayman AV; Stocker SJ; Baker MS; Bentrem DJ; Prinz RA; Marsh RD; Talamonti MS

INSTITUCIÓN / INSTITUTION:  - *Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago daggerDepartment of Surgery, NorthShore University HealthSystem double daggerDepartment of Medicine, Division of Hematology/Oncology, NorthShore University HealthSystem, Evanston, IL.

RESUMEN / SUMMARY:  - BACKGROUND:: Carbohydrate antigen (CA) 19-9 is the most common serum biomarker used in pancreatic adenocarcinoma (PC). Elevated preoperative levels have been shown to correlate with more advanced stage, greater risk of unresectability, and overall worse survival. The prognostic value of CA 19-9 nonproduction, which is present in an estimated 5% to 15% of the population, is unclear. We sought to determine whether CA 19-9 nonproduction was associated with worse survival after  PC resection. METHODS:: We retrospectively reviewed our institution’s prospective pancreatic database for all PC patients with documented preoperative CA 19-9 values who underwent resection with curative intent from March 1992 to August 2009. After excluding 10 perioperative deaths, 200 patients remained for analysis. RESULTS:: Mean and median follow-up was 23.3 and 16.1 months, respectively. Median survival in months for patients with preoperative CA 19-9 levels in U/mL by category was as follows: normal (5.1 to 36.9): 32, nonproduction (</=5): 21, mildly elevated (37 to 99.9): 35, highly elevated (100+): 16. Factors significantly associated with worse overall survival were: nonwhite race, nonproduction or highly elevated preoperative CA 19-9 (>/=100 U/mL), estimated blood loss >/=1 L, tumor size (>/=2 cm), lymph node-positivity,  and advanced (3/4) histologic grade. On multivariate analysis, only CA 19-9 nonproduction or highly elevated production, estimated blood loss >/=1 L, advanced histologic grade, and node positivity remained significant in the final  model. CONCLUSIONS:: CA 19-9 nonproduction is not associated with improved survival after pancreatic cancer resection, as has previously been asserted, when compared with patients with normal and elevated levels.

 

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[145]

TÍTULO / TITLE:  - Lipocalin-2 is Associated With a Good Prognosis and Reversing Epithelial-to-Mesenchymal Transition in Pancreatic Cancer.

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

REVISTA / JOURNAL:  - World J Surg. 2013 Mar 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00268-013-2009-6

AUTORES / AUTHORS:  - Xu B; Jin DY; Lou WH; Wang DS

INSTITUCIÓN / INSTITUTION:  - Department of Hepato-biliary-pancreatic Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China, pfdbs1@yahoo.com.cn.

RESUMEN / SUMMARY:  - BACKGROUND: Lipocalin-2 is a multifaceted modulator in cancer progression. Its clinical significance is not clear in pancreatic cancer. The purpose of this study was to investigate whether lipocalin-2 is associated with good prognosis by reversing epithelial-to-mesenchymal transition (EMT) in pancreatic cancer. METHODS: Lipocalin-2, E-cadherin, or vimentin expression was detected in 60 pancreatic adenocarcinoma specimens. Correlations between lipocalin-2 expression  and EMT, the clinicopathologic characteristics, and prognosis were investigated.  Whether pancreatic cancer cells’ migration and invasion (some characteristics of  EMT) were affected by lipocalin-2 was also explored. RESULTS: High lipocalin-2 expression was significantly associated with a good prognosis in pancreatic cancer (p < 0.05). Overexpression of lipocalin-2 correlated with a lower extent of EMT (p < 0.05), increased E-cadherin expression (p < 0.05), decreased vimentin expression (p < 0.05), and reduced cancer cell migration and invasion in pancreatic cancer. CONCLUSIONS: Lipocalin-2 may be considered an epithelial inducer, which may reverse EMT and predict a good prognosis in pancreatic cancer.

 

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[146]

TÍTULO / TITLE:  - Induction of pancreatic cancer cell apoptosis, invasion, migration, and enhancement of chemotherapy sensitivity of gemcitabine, 5-FU, and oxaliplatin by  hnRNP A2/B1 siRNA.

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

REVISTA / JOURNAL:  - Anticancer Drugs. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e3283608bc5

AUTORES / AUTHORS:  - Gu WJ; Liu HL

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, the Ninth People’s Hospital, School of Medicine,  Shanghai Jiao Tong University, Shanghai, China.

RESUMEN / SUMMARY:  - We investigated the effects of inhibiting heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) expression on apoptosis, invasion, migration, and the chemotherapy sensitivity of pancreatic cancer cells to gemcitabine, 5-FU, and oxaliplatin chemotherapy using small interfering RNA (siRNA). Chemically synthesized siRNA hnRNP A2/B1 was transfected into the human pancreatic cancer cell lines SW1990 and BxPC-3. The IC50 of gemcitabine, 5-FU, and oxaliplatin was  determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis and cycle were detected using flow cytometry. The expressions of apoptosis-related genes, p53, Bax, Bcl-2, TRAIL, Survivin, multidrug resistance 1 (MDR1), E-cadherin, and matrix metalloproteinases-2 (MMP-2) were detected using real-time PCR and western blot. Plate colony formation assay, wound scratch assay, invasion, and migration were also examined. Gemcitabine, 5-FU, and oxaliplatin inhibit the proliferation of SW1990 and BxPC-3 cells in a concentration-dependent manner. Inhibition of hnRNP A2/B1 expression significantly reduced the IC50 of gemcitabine, 5-FU, and oxaliplatin (P<0.01). hnRNP A2/B1 siRNA combined with gemcitabine, 5-FU and Oxaliplatin significantly increased (P<0.01) apoptosis of pancreatic cancer cell lines SW1990 and BxPC-3, increased the expression level of Bax mRNA, decreased Bcl-2 mRNA and MDR1 mRNA expression (P<0.01), and induced no change in p53, TRAIL, and Survivin mRNA expression in SW1990. In the western blot analysis, the expression level of Bax protein increased (P<0.01); the expression of both P-glycoprotein (Pg-p) protein  and Bcl-2 protein decreased (P<0.01). Silencing hnRNP A2/B1 decreased invasion and migration in the cell line SW1990. Silencing hnRNP A2/B1 in SW1990 also correlated with an increase in E-cadherin expression and a decrease in MMP-2 expression at the same time. Inhibition of hnRNP A2/B1 expression can induce apoptosis in pancreatic cancer cells and improve chemosensitivity to gemcitabine, 5-FU, and oxaliplatin. hnRNP A2/B1 may play a role in invasion and migration in the pancreatic cancer cell line SW1990 through the regulation of E-cadherin and expression of MMP-2.

 

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[147]

TÍTULO / TITLE:  - Role of Insulin and Igf signaling in pancreatic cancer.

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

REVISTA / JOURNAL:  - J Mol Endocrinol. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1530/JME-12-0259

AUTORES / AUTHORS:  - Trajkovic-Arsic M; Kalideris E; Siveke JT

INSTITUCIÓN / INSTITUTION:  - M Trajkovic-Arsic, II Medical department, Klinikum rechts der Isar, Munich, Germany.

RESUMEN / SUMMARY:  - Abstract The importance of the insulin-like growth factor system in carcinogenesis has been established for many solid cancers. It is well known that individuals with higher circulating levels of the insulin-like growth factor 1(IGF1) ligand present an increased risk of cancer. However, therapies with monoclonal antibodies targeting the IGF1 receptor (IGF1R) have been largely unsuccessful. One of the potential reasons for this failure is the existence of the highly homologous insulin receptor (IR) which appears to be at least as equally efficient as the IGF1R in the transition of mitogenic signals to the nucleus and promotion of cell growth. Furthermore, IGF1 and insulin receptors can form hybrid receptors sensitive to stimulation of all three ligands of the system: insulin, insulin-like growth factor 1 and insulin-like growth factor 2. Although the connection between insulin, diabetes and cancer has been established for years now, clear evidence that demonstrate the redundancy of insulin and insulin receptors and insulin-like growth factors and their receptors in cancer are missing. In this review, we focus on the contribution of insulin and IGFs to  carcinogenesis in the insulin-producing organ, the pancreas. We give a short summary on the complexity of insulin and the IGF system in the pancreas and their potential roles in pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC). Finally, we discuss drug targeting options of this system and the rationale of simultaneous targeting of both the insulin and IGF systems.

 

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[148]

TÍTULO / TITLE:  - Identification and impact of hepatitis B virus DNA and antigens in pancreatic cancer tissues and adjacent non-cancerous tissues.

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

REVISTA / JOURNAL:  - Cancer Lett. 2013 Mar 7. pii: S0304-3835(13)00224-3. doi: 10.1016/j.canlet.2013.03.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.03.001

AUTORES / AUTHORS:  - Jin Y; Gao H; Chen H; Wang J; Chen M; Li G; Wang L; Gu J; Tu H

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Diagnostics, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

RESUMEN / SUMMARY:  - Increasing evidence suggests that a link exists between hepatitis B virus (HBV) serum markers and pancreatic cancer (PC). In this study, HBsAg and HBcAg were expressed in 21.0% (34/162) of PC and 29.0% (47/162) of non-tumor pancreatic tissues, and they were significantly associated with chronic pancreatitis (P=0.000). The HBV S, C and X genes were identified in 20% (6/30) of PC and 26.9% (7/26) of non-tumor tissues by PCR. A serological survey revealed that the prevalence of HBV DNA and anti-HBc was significantly increased in PC patients compared with healthy controls. Our data suggest that HBV infection in the pancreas may play an etiologic role in PC.

 

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[149]

TÍTULO / TITLE:  - Contrast-Enhanced Ultrasound in the Differential Diagnosis of Exocrine Versus Neuroendocrine Pancreatic Tumors.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31827a7b01

AUTORES / AUTHORS:  - Serra C; Felicani C; Mazzotta E; Piscitelli L; Cipollini ML; Tomassetti P; Pezzilli R; Casadei R; Morselli-Labate AM; Stanghellini V; Corinaldesi R; De Giorgio R

INSTITUCIÓN / INSTITUTION:  - From the *Department of Medical and Surgical Sciences/Digestive Diseases and Internal Medicine, St Orsola-Malpighi Hospital; daggerDivision of Angiology and Blood Coagulation, and double daggerDepartment of Medical and Surgical Sciences,  St Orsola-Malpighi Hospital; and section signCentro Interdipartimentale di Ricerca sull Alimentazione Umana (CIRAU), University of Bologna; Bologna, Italy.

RESUMEN / SUMMARY:  - OBJECTIVES: Contrast-enhanced ultrasound (CEUS) has been developed to better characterize the microvasculature of solid masses in several organs, including the pancreas. In this study, we assessed CEUS accuracy in differentiating exocrine from endocrine pancreatic tumors. METHODS: A total of 127 patients with  single, undetermined pancreatic masses were prospectively examined with transabdominal ultrasound and CEUS, before surgical resection or percutaneous biopsy. RESULTS: Exocrine and endocrine pancreatic tumors showed different intralesional vascularization patterns: 98.9% (90/91) of exocrine tumors were hypoenhancing, whereas 95.8 % (23/24) of endocrine tumors had a hypervascular supply. A hypoenhancing pattern, indicative of ductal adenocarcinoma, had a significant (P < 0.001) diagnostic accuracy of 91.3% with a sensitivity of 96.8%, a specificity of 85.3%, a positive predictive value and a negative predictive value of 94.7% and 90.6%, respectively. The hyperenhancing pattern, indicative of endocrine tumors, had a significant (P = 0.031) diagnostic accuracy of 73.8% with a sensitivity of 83.3%, a specificity of 60.0%, a positive predictive value and negative predictive value of 83.3% and 60.0%, respectively. CONCLUSIONS: Contrast-enhanced ultrasound has a valuable diagnostic accuracy in differentiating exocrine from endocrine pancreatic tumors, which is a fundamental step to address appropriate histological evaluation, therapeutic approach, and follow-up.

 

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[150]

TÍTULO / TITLE:  - Virtual analysis of pancreatic cystic lesion fluid content by ultrasound acoustic radiation force impulse quantification.

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

REVISTA / JOURNAL:  - J Ultrasound Med. 2013 Apr;32(4):647-51.

AUTORES / AUTHORS:  - D’Onofrio M; Crosara S; Canestrini S; Demozzi E; De Robertis R; Salvia R; Bassi C; Mucelli RP

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, University Hospital G. B. Rossi, University of Verona, Piazzale L. A. Scuro 10, 37134 Verona, Italy. mirko.donofrio@univr.it.

RESUMEN / SUMMARY:  - Objectives The purpose of this study was to prospectively evaluate the application of acoustic radiation force impulse (ARFI) imaging implemented with Virtual Touch tissue quantification (Siemens AG, Erlangen, Germany) in the study  of pancreatic cystic lesions by using different analysis methods compared with the final diagnosis (pathologic or by magnetic resonance imaging and endoscopic sonographic findings). Methods Thirty-eight patients with pancreatic cystic focal lesions (diameter >3 cm and located at a depth of 5.5 cm) were included in the study and underwent conventional sonography. For every patient, 5 measurements in the Virtual Touch tissue quantification region of interest were obtained. To distinguish mucinous (potentially malignant) from serous (mainly benign) cystic lesions, the result XXXX/0 was considered to mean simple liquids (comparable to water), and the accuracy of Virtual Touch tissue quantification in differentiating pancreatic cystic lesions was calculated. To consider a lesion as containing complex fluids (potentially mucinous), two different reading methods were applied: (1) at least 2 numerical values when obtaining 5 measurements; and  (2) the prevalence of numerical values irrespective of the number of measurements. The sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for the differential diagnosis between mucinous and nonmucinous cystic lesions. Results By the first reading method, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the group of cystic lesions were 68.8%, 77.3%, 68.8%, 77.3%, and  73.7%, respectively; by the second method, the values were 37.5%, 100%, 100%, 68.8%, and 73.3%. Conclusions Acoustic radiation force impulse imaging with Virtual Touch tissue quantification can have a role in the noninvasive characterization of pancreatic cystic lesions during conventional sonographic examinations.

 

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[151]

TÍTULO / TITLE:  - Is extended hemihepatectomy plus pancreaticoduodenectomy justified for advanced bile duct cancer and gallbladder cancer?

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

REVISTA / JOURNAL:  - Surgery. 2013 Feb 13. pii: S0039-6060(12)00737-4. doi: 10.1016/j.surg.2012.11.024.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2012.11.024

AUTORES / AUTHORS:  - Sakamoto Y; Nara S; Kishi Y; Esaki M; Shimada K; Kokudo N; Kosuge T

INSTITUCIÓN / INSTITUTION:  - Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: yosakamo-tky@umin.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: Major hepatopancreaticoduodenectomy (HPD) is an extensive surgical procedure offering the highest curability for patients with advanced biliary cancer. However, surgical morbidity associated with major HPD is high, and optimal indications for this procedure remain unclear. METHODS: Between 1989 and  2010, 14 patients with widespread bile duct cancer and 5 with gallbladder cancer  having biliary infiltration underwent major HPD at our hospital. Preoperative portal vein embolization was performed in 17 patients undergoing right HPD. Clinicopathologic factors and survivals following HPD were compared between patients with bile duct cancer and those with gallbladder cancer. RESULTS: One patient who underwent right HPD for gallbladder cancer died of hepatic failure (5.3%) and 18 of the 19 patients (95%) developed postoperative pancreatic fistulas. The median hospital stay was 47 days. Depth of invasion was T3 in 1 patient and T4 in 2 patients with bile duct cancer and was T4 in all 5 patients with gallbladder cancer (P = .002). The clinical stage was IV in 3 patients (21%) with bile duct cancer and in all 5 patients with gallbladder cancer (P = .002). The 5-year survival rates and median survival rates of patients with bile duct cancer and gallbladder cancer were 45% vs 0 and 3.3 years vs 8 months, respectively (P < .001). CONCLUSION: HPD can be an acceptable treatment option for widespread bile duct cancer. However, the indication for HPD in advanced-stage gallbladder cancer should be considered carefully, considering the high morbidity rate and the advanced stage of the disease.

 

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[152]

TÍTULO / TITLE:  - Histopathologic findings of multifocal pancreatic intraductal papillary mucinous  neoplasms on CT.

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

REVISTA / JOURNAL:  - AJR Am J Roentgenol. 2013 Mar;200(3):563-9. doi: 10.2214/AJR.12.8924.

            ●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.8924

AUTORES / AUTHORS:  - Raman SP; Kawamoto S; Blackford A; Hruban RH; O’Brien-Lennon AM; Wolfgang CL; Rezaee N; Edil B; Fishman EK

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Johns Hopkins University, 601 N Caroline St, JHOC 3251,  Baltimore, MD 21287, USA. srsraman3@gmail.com

RESUMEN / SUMMARY:  - OBJECTIVE: The criteria for resection of solitary pancreatic side-branch intraductal papillary mucinous neoplasm (IPMN) have been well described by the Sendai consensus statement. However, the management of multiple pancreatic cystic lesions is less certain, with no clear guidelines in the literature to date. The  purpose of this study was to evaluate the histopathologic findings in pancreatic  IPMNs in patients with multiple (>/= 4) pancreatic cysts. MATERIALS AND METHODS:  The CT scans of all patients with a pathologically proven IPMN at our institution were reviewed, and a total of 52 patients with four or more pancreatic cysts were found. Each case was reviewed for the number of cysts and the presence of signs of invasive malignancy including a coexistent solid pancreatic mass, pancreatic ductal dilatation, and mural nodularity. RESULTS: A total of 52 patients (19 men, 33 women; mean age, 71.8 years) were found to have multifocal IPMNs, defined as four or more cysts, on CT. Of these 52 patients, nine also had evidence of a solid pancreatic mass on CT. Retrospective review of the pathologic results for the remaining 43 patients (17 men, 26 women; mean age, 71.76 years) showed 18 cases of an IPMN with either high-grade dysplasia or a coexistent invasive carcinoma. Most important, 37% (7/19 patients) had no CT findings of an invasive  malignancy according to the Sendai criteria (i.e., cysts >/= 3 cm in the axial plane, main pancreatic ductal dilatation >/= 6 mm, or mural nodularity within a cyst) but were found to have an IPMN with either high-grade dysplasia or invasive carcinoma. When the pancreas contained 10 or more cysts, high-grade dysplasia or  invasive carcinoma tended to be more likely than low- or intermediate-grade dysplasia (odds ratio, 3.83; 95% CI, 0.87-16.8; p = 0.075). CONCLUSION: The presence of multiple pancreatic cysts should be looked on with suspicion, particularly when there are a large number of cysts, even when none of the cysts  individually meet the imaging criteria for resection according to the Sendai consensus recommendations. At the very least, these patients need to be followed  very closely.

 

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[153]

TÍTULO / TITLE:  - Differences in Transcript Levels of ABC Transporters Between Pancreatic Adenocarcinoma and Nonneoplastic Tissues.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279b861

AUTORES / AUTHORS:  - Mohelnikova-Duchonova B; Brynychova V; Oliverius M; Honsova E; Kala Z; Muckova K; Soucek P

INSTITUCIÓN / INSTITUTION:  - From the *Department of Toxicogenomics, National Institute of Public Health, Prague; daggerDepartment of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc; double dagger3rd Faculty of Medicine, Charles University, Prague, Czech Republic; Departments of section signTransplantation Surgery and parallelClinical and Transplantation Pathology, Institute of Clinical and Experimental Medicine, Prague; and Departments of paragraph signSurgery and #Pathology, Masaryk University Hospital and Faculty of Medicine, Brno Bohunice.

RESUMEN / SUMMARY:  - OBJECTIVES: The aim of this study was to evaluate transcript levels of all 49 human ATP-binding cassette transporters (ABCs) in one of the most drug-resistant  cancers, namely, the pancreatic ductal adenocarcinoma (PDAC). Association of ABCs levels with clinical-pathologic characteristics and KRAS mutation status was followed as well. METHODS: Tumors and adjacent nonneoplastic tissues were obtained from 32 histologically verified PDAC patients. The transcript profile of ABCs was assessed using quantitative real-time polymerase chain reaction with a relative standard curve. KRAS mutations in exon 2 were assessed by high-resolution melting analysis and sequencing. RESULTS: Most ABCs were deregulated in PDAC and 10 ABCs were associated with clinical-pathologic characteristics. KRAS mutations did not change the global expression profile of ABCs. CONCLUSIONS: The expression of ABC transporters was significantly deregulated in PDAC tumors when compared to nonmalignant tissues. The observed up-regulation of ABCB4, ABCB11, ABCC1, ABCC3, ABCC5, ABCC10, and ABCG2 in tumors  may contribute to the generally poor treatment response of PDAC. The up-regulation of ABCA1, ABCA7, and ABCG1 implicates a serious impairment of cellular cholesterol homeostasis in PDAC. On the other hand, the observed down-regulation of ABCA3, ABCC6, ABCC7, and ABCC8 suggests a possible role of stem cells in the development and progression of PDAC.

 

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[154]

TÍTULO / TITLE:  - A rare case of transient hypercortisolemia resulting from an inflammatory adrenal mass following acute pancreatitis.

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

REVISTA / JOURNAL:  - Endocrine. 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12020-013-9900-7

AUTORES / AUTHORS:  - Miyata M; Yoshida M; Ueda H; Fukuoka K; Oiso Y

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology and Diabetes, Nagoya Ekisaikai Hospital, 4-66 Shounen-cho, Nakagawa-ku, Nagoya, 454-8502, Japan.

 

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[155]

TÍTULO / TITLE:  - Pancreatic cancer-associated Cathepsin E as a drug activator.

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

REVISTA / JOURNAL:  - J Control Release. 2013 Feb 26;167(3):221-227. doi: 10.1016/j.jconrel.2013.02.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jconrel.2013.02.007

AUTORES / AUTHORS:  - Abd-Elgaliel WR; Cruz-Monserrate Z; Wang H; Logsdon CD; Tung CH

INSTITUCIÓN / INSTITUTION:  - Department of Translational Imaging, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, USA.

RESUMEN / SUMMARY:  - Pancreatic ductal adenocarcinoma (PDAC) is challenging to treat, and better means to detect and/or treat pancreatic cancer are urgently needed to save lives. Cathepsin E (Cath E) is a proteolytic enzyme highly expressed in PDAC. In this study, a novel approach using Cath E activation of a Cath E-specific prodrug was  demonstrated. Specific activation of the prodrug is expected to kill pancreatic cancer cells without harming normal pancreatic cells. A novel 5-aminolevulinic acid (5-ALA) prodrug was custom-designed to be activated selectively by endogenous Cath E within the PDAC cells. The 5-ALA prodrug was incubated with Cath E-positive and -negative tumor cells and illuminated with various doses of light. In addition, mice genetically engineered to develop PDAC were injected intravenously with the 5-ALA prodrug, and the pancreas was treated with light irradiation. One day after treatment, PDAC tissue was assessed for apoptosis. The 5-ALA prodrug was activated within the Cath E-positive tumor but not in the normal pancreatic tissue. When used in combination with light treatment, it allowed delivery of selective photodynamic therapy (PDT) to the cancerous tissues, with minimal harm to the adjacent normal tissues. With this novel Cath E activation approach, it is possible to detect pancreatic cancer cells accurately  and specifically impair their viability, while sparing normal cells. This treatment could result in fewer side effects than the non-specific treatments currently in use. Cath E is a specific and effective drug activator for PDAC treatment.

 

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[156]

TÍTULO / TITLE:  - Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center at Columbia University experience.

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

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Mar;71(3):663-70. doi: 10.1007/s00280-012-2055-z. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-012-2055-z

AUTORES / AUTHORS:  - Fine RL; Gulati AP; Krantz BA; Moss RA; Schreibman S; Tsushima DA; Mowatt KB; Dinnen RD; Mao Y; Stevens PD; Schrope B; Allendorf J; Lee JA; Sherman WH; Chabot JA

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, Experimental Therapeutics Program, The Pancreas Center at Columbia, New York Presbyterian-Columbia University Medical Center, New York, NY 10032, USA. rlf20@columbia.edu

RESUMEN / SUMMARY:  - PURPOSE: We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ). METHODS: A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LAR (100%), chemotherapy (61%), and hepatic chemoembolization (50%).  Patients received capecitabine at 600 mg/m(2) orally twice daily on days 1-14 (maximum 1,000 mg orally twice daily) and TMZ 150-200 mg/m(2) divided into two doses daily on days 10-14 of a 28-day cycle. Imaging was performed every 2 cycles, and serum tumor markers were measured every cycle. RESULTS: Using RECIST  parameters, 1 patient (5.5%) with midgut carcinoid achieved a surgically proven complete pathological response (CR), 10 patients (55.5%) achieved a partial response (PR), and 4 patients (22.2%) had stable disease (SD). Total response rate was 61%, and clinical benefit (responders and SD) was 83.2%. Of four carcinoid cases treated with CAPTEM, there was 1 CR, 1 PR, 1 SD, and 1 progressive disease. Median progression-free survival was 14.0 months (11.3-18.0  months). Median overall survival from diagnosis of liver metastases was 83 months (28-140 months). The only grade 3 toxicity was thrombocytopenia (11%). There were no grade 4 toxicities, hospitalizations, opportunistic infections, febrile neutropenias, or deaths. CONCLUSIONS: CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.

 

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[157]

- CASTELLANO -

TÍTULO / TITLE:Pseudoquiste pancreatico fistulizado a cavidad pleural. Una rara causa de derrame pleural masivo.

TÍTULO / TITLE:  - Pancreatic pseudocyst fistulised to pleural space: A rare cause of a massive pleural effusion.

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

REVISTA / JOURNAL:  - Cir Esp. 2013 Feb 26. pii: S0009-739X(13)00030-4. doi: 10.1016/j.ciresp.2012.11.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ciresp.2012.11.009

AUTORES / AUTHORS:  - Caballero Rodriguez E; Hidalgo Rodriguez MA; Herrero Collantes J; Garcia Franco CE

INSTITUCIÓN / INSTITUTION:  - Servicio de Cirugia Gral y del Aparato Digestivo, Hospital Universitario Nuestra  Senora de Candelaria, Santa Cruz de Tenerife, España. Electronic address: eugenia0005@gmail.com.

 

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[158]

TÍTULO / TITLE:  - The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Apr;29(4):1671-7. doi: 10.3892/or.2013.2276. Epub 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2276

AUTORES / AUTHORS:  - Thakkar A; Sutaria D; Grandhi BK; Wang J; Prabhu S

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.

RESUMEN / SUMMARY:  - Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with ~37,000 deaths each year. The present study evaluated the chemopreventive potential of a combination of aspirin (ASP), curcumin (CUR) and sulforaphane (SFN) in low doses to human pancreatic cancer cells, MIA PaCa-2 and  Panc-1. Results demonstrated that low doses of ASP (1 mM), CUR (10 microM) and SFN (5 microM) (ACS) combination reduced cell viability by ~70% (P<0.001), and also induced cell apoptosis by ~51% (P<0.001) accompanied by activation of caspase-3 and Poly(ADP-ribose) polymerase (PARP) proteins. The NF-kappaB DNA binding activity was inhi-bited by ~45% (P<0.01) and ~75% (P<0.001) in MIA PaCa-2 and Panc-1 cells, respectively. Mechanistic studies revealed that ACS promoted increase expression of phospho extracellular signal-regulated kinase ½ (P-ERK1/2), c-Jun, p38 MAPK and p53 proteins. Furthermore, the cells pretreated with U0126 (ERK1/2 inhibitor) partially abolished the effect of ACS on cell viability. Data from this study demonstrate that a low-dose ACS combination inhibits cell growth by inducing cell apoptosis, and proposes sustained activation of the ERK1/2 signaling pathway as one of the possible mechanisms.

 

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[159]

TÍTULO / TITLE:  - Tumor Necrosis Factor-alpha Levels Early in Severe Acute Pancreatitis: Is There Predictive Value Regarding Severity and Outcome?

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

REVISTA / JOURNAL:  - J Clin Gastroenterol. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MCG.0b013e31828a6cfc

AUTORES / AUTHORS:  - Surbatovic M; Radakovic S

INSTITUCIÓN / INSTITUTION:  - *Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy daggerFaculty of Medicine of the Military Medical Academy, University of Defense  double daggerSector of Preventive Medicine, Military Medical Academy, Belgrade, Serbia.

RESUMEN / SUMMARY:  - GOAL AND BACKGROUND:: One of the most important cytokines in pathogenesis of acute pancreatitis is tumor necrosis factor (TNF)-alpha. The aim of our study was to determine whether the plasma levels of TNF-alpha in patients with severe acute pancreatitis (SAP) on admission correlate with severity and outcome of SAP. STUDY:: Blood samples were obtained from 100 patients with SAP. Patients were divided into 2 groups according to severity: SAP group (n=69) and SAP-induced multiple organ dysfunction syndrome (MODS) group (n=31). Survivors were patients  who were alive 90 days after taking the blood sample for cytokine measurement (53/100). Blood sample for cytokine measurement was drawn immediately after admission. TNF-alpha was measured by commercial ELISA test in plasma. RESULTS:: When comparing SAP group with SAP-induced MODS group, we found that mean values of TNF-alpha on admission were 191.5-fold lower in group with SAP-induced MODS (P<0.01). When comparing nonsurvivors with survivors, we found that mean values of TNF-alpha on admission were 63-fold higher in survivors (P<0.01). At cut-off level of 7.95 pg/mL sensitivity was 83.9% and specificity was 72.5%. Patients with TNF-alpha level lower than 7.95 pg/mL had 3.2-fold higher probability to develop SAP with MODS. At cut-off level of 10.5 pg/mL sensitivity was 83% and specificity was 77.4%. Patients with TNF-alpha level higher than 10.5 pg/mL had 4.8-fold higher probability to survive. CONCLUSIONS:: TNF-alpha is good predictor of severity and outcome. Low TNF-alpha concentration in patients with SAP predicts development of MODS and fatal outcome.

 

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[160]

TÍTULO / TITLE:  - Pancreatic cancer and supportive care-pancreatic exocrine insufficiency negatively impacts on quality of life.

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

REVISTA / JOURNAL:  - Support Care Cancer. 2013 Feb 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00520-013-1729-3

AUTORES / AUTHORS:  - Gooden HM; White KJ

INSTITUCIÓN / INSTITUTION:  - Cancer Nursing Research Unit, Sydney Nursing School, University of Sydney, Camperdown, Australia, helen.gooden@sydney.edu.au.

RESUMEN / SUMMARY:  - PURPOSE: Pancreatic cancer is a fatal cancer with a median survival from diagnosis of around 5 months Speer et al. (Med J Aust 196(8):511-515, 2012). Given the short survival time for people with pancreatic cancer, effective supportive care is imperative to enable best quality of life. This article presents an unexpected finding from research into the psychosocial supportive care needs of people affected by pancreatic cancer that management of pancreatic  exocrine insufficiency is an area of unmet need that severely impacts on quality  of life and increases carer burden in people affected by pancreatic cancer. METHODS: A qualitative inquiry framework was used to explore participants’ perspectives and experience. Two groups of participants (N = 35) were recruited across Australia from people accessing the Cancer Helpline or direct referral from clinicians/nurses: patients diagnosed with pancreatic cancer (N = 12) and carers/family (N = 23) including a subgroup of bereaved participants (N = 14). Sampling continued until saturation. A thematic content analysis was conducted. RESULTS: The findings revealed that the major quality of life theme was difficulty in managing gut symptoms and complex dietary issues. Issues were related to lack of information about malabsorption and managing symptoms of pancreatic exocrine insufficiency. This was compounded by a lack of routine dietary consultation: perceived reluctance of clinicians to prescribe enzyme supplements and poor understanding of dose to diet guidelines. CONCLUSION: Participants expressed distress relating to the effects of pancreatic exocrine insufficiency. Pancreatic enzyme supplement therapy with clear dosage guidelines  and associated dietary advice could resolve symptoms of malabsorption and markedly improve quality of life. For people affected by pancreatic cancer, this  is an essential supportive care.

 

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[161]

TÍTULO / TITLE:  - Pancreatic neuroendocrine tumor with cystlike changes: evaluation with MDCT.

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

REVISTA / JOURNAL:  - AJR Am J Roentgenol. 2013 Mar;200(3):W283-90. doi: 10.2214/AJR.12.8941.

            ●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.8941

AUTORES / AUTHORS:  - Kawamoto S; Johnson PT; Shi C; Singhi AD; Hruban RH; Wolfgang CL; Edil BH; Fishman EK

INSTITUCIÓN / INSTITUTION:  - The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N Caroline St, JHOC 3235A, Baltimore,  MD 21287, USA. skawamo1@jhmi.edu

RESUMEN / SUMMARY:  - OBJECTIVE: The objective of our study was to determine the prevalence and CT appearance of cystlike changes of pancreatic neuroendocrine tumor (NET), particularly of small (</= 3 cm) tumors. MATERIALS AND METHODS: The clinical records, images, and pathologic reports of 74 consecutive patients (average age,  55.5 years) with surgically resected pancreatic NETs who underwent preoperative CT were retrospectively reviewed. The size and location of the pancreatic NETs were recorded. The tumors were classified on the basis of CT appearance as small  (</= 3 cm) or large (> 3 cm) and as solid, partially (</= 50% or > 50%) cystic, or purely ( approximately 100%) cystic. Peripheral contrast enhancement on CT was characterized, and lymph node and liver metastases found by pathologic examination were recorded. RESULTS: A total of 78 pancreatic NETs were reviewed.  Five were not visualized on CT, leaving 73 pancreatic NETs in 69 patients (multiple tumors were visualized on CT of three patients) for analysis. The mean  size of the 73 tumors was 3.0 +/- 2.6 (SD) cm (range, 0.7-13.1 cm); 52 tumors were 3 cm or smaller and 21 tumors were larger than 3 cm. Gross pathologic results confirmed that 13 of the 73 (17.8%) tumors were predominantly (> 50% or approximately 100%) cystic: 10 of the 52 (19.2%) tumors 3 cm or smaller and three of the 21 (14.3%) tumors larger than 3 cm. Peripheral contrast enhancement was seen in 11 of the 13 (85%) predominantly cystic pancreatic NETs. Compared with solid pancreatic NETs, predominantly cystic pancreatic NETs were less commonly associated with lymph node and liver metastases. CONCLUSION: Cystic pancreatic NETs are not rare and should be included in the differential diagnosis of a cystic pancreatic mass, particularly if the cystic mass is associated with peripheral contrast enhancement. A minority of cystic pancreatic NETs can present with no peripheral enhancement.

 

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[162]

TÍTULO / TITLE:  - Retrospective study of gemcitabine plus S-1 versus gemcitabine alone in cases with unresectable advanced pancreatic cancer.

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

REVISTA / JOURNAL:  - Hepatogastroenterology. 2013 Mar 11;60(127). doi: 10.5754/hge121235.

            ●● Enlace al texto completo (gratuito o de pago) 5754/hge121235

AUTORES / AUTHORS:  - Suzuki S

 

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[163]

TÍTULO / TITLE:  - The CT findings of pancreatic acinar cell carcinoma in five cases.

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

REVISTA / JOURNAL:  - Clin Imaging. 2013 Mar;37(2):302-7. doi: 10.1016/j.clinimag.2012.06.003. Epub 2012 Jul 15.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.06.003

AUTORES / AUTHORS:  - Liu K; Peng W; Zhou Z

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

RESUMEN / SUMMARY:  - OBJECTIVES: The aim of this study is to analyze the computed tomographic (CT) findings of pancreatic acinar cell carcinoma (ACC). MATERIALS AND METHODS: The CT features and clinical presentations of five patients (four men, one woman; mean age, 52 years) with pathology-proven pancreatic ACC were reviewed. The image characteristics included the lesion location and size, the exophytic nature of the tumor, intratumoral hemorrhage, calcification, the presence of cystic or necrotic components, bile or pancreatic duct dilation, attenuation on the noncontrast image, attenuation on the arterial- and venous-phase images, peripancreatic invasion, peripancreatic lymphadenopathy, and distant metastases.  RESULTS: The tumors were located at the pancreatic tail in three cases and at the pancreatic head in two cases. The average lesion size was 5.3 cm. Exophytic features and cystic/necrotic components were found in 80% (4/5) and 60% (3/5) of  cases, respectively. The ACC showed a mild hypodense appearance on noncontrast CT in 100% (3/3) of cases and a hypodense appearance on arterial-/venous-phase CT in 80% (4/5) of cases. The exception was one lesion that showed a significantly hyperdense appearance and a mildly hyperdense appearance on the arterial- and venous-phase images. None of the CT images showed enhancement of a capsule, calcification, intratumoral hemorrhage, bile or pancreatic duct dilation, vascular encasement, or distant metastatic disease, but three cases showed peripancreatic invasion and lymphadenopathy. CONCLUSIONS: With persistent mild enhancement, the typical ACC appears as an exophytic tumor with a focal cystic/necrotic component and the lack of ductal dilatation. The predilection for older male patients and elevated serum alpha fetoprotein are useful clinical features for confirming an ACC diagnosis.

 

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[164]

TÍTULO / TITLE:  - Glucagonoma with necrolytic migratory erythema exhibiting responsiveness to subcutaneous octreotide injections.

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

REVISTA / JOURNAL:  - QJM. 2013 Feb 6.

            ●● Enlace al texto completo (gratuito o de pago) 1093/qjmed/hct027

AUTORES / AUTHORS:  - Lo CH; Ho CL; Shih YL

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine.

 

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[165]

TÍTULO / TITLE:  - Laparoscopic Partial Sleeve Duodenectomy (PSD) for Nonampullary Duodenal Neoplasms: Avoiding a Whipple by Separating the Duodenum from the Pancreatic Head.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Apr;42(3):461-6. doi: 10.1097/MPA.0b013e3182649956.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e3182649956

AUTORES / AUTHORS:  - Stauffer JA; Raimondo M; Woodward TA; Goldberg RF; Bowers SP; Asbun HJ

INSTITUCIÓN / INSTITUTION:  - From the Departments of *General Surgery, and daggerGastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL.

RESUMEN / SUMMARY:  - OBJECTIVE: To learn the clinical outcome of patients undergoing laparoscopic partial sleeve duodenectomy (PSD) for lesions, which require sleeve resection of  the duodenum. Traditionally, these lesions require en bloc excision of the head of the pancreas performed in an open fashion. METHODS: A retrospective review of  medical records of patients with nonampullary large or circumferential duodenal lesions, which were not amenable to endoscopic or local resection for complete removal, was performed. Characteristics, complications, and technical details were analyzed. RESULTS: Ten patients (5 men and 5 women; mean age, 70 years) with duodenal lesions including adenoma (n = 5), adenocarcinoma (n = 2), lymphangiolipoma (n = 1), leiomyoma (n = 1), and neuroendocrine tumor (n = 1) were included. All patients underwent a laparoscopic approach with either a proximal PSD (n = 3) or distal PSD (n = 7) after separation of the duodenum from  the pancreatic head. Reconstruction was carried out by a side-to-side duodenojejunostomy (n = 7), end-to-side duodenojejunostomy (n = 2), or gastrojejunostomy (n = 1). Mean length of stay was 5.6 days, and complications were 20%. CONCLUSIONS: Laparoscopic PSD seems to be a safe and easily applicable  technique for treatment of duodenal lesions not involving the ampulla, which requires separation of the duodenum from the pancreas head with sleeve resection  of the duodenum and subsequent reconstruction.

 

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[166]

TÍTULO / TITLE:  - Pancreatic Endocrine Tumour with Disseminated Pulmonary Thromboembolism in an Owl Monkey (Aotus nancymae).

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

REVISTA / JOURNAL:  - J Comp Pathol. 2013 Feb 28. pii: S0021-9975(12)00423-9. doi: 10.1016/j.jcpa.2012.11.235.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jcpa.2012.11.235

AUTORES / AUTHORS:  - Gozalo AS; Zerfas PM; Starost MF; Lambert LE; Elkins WR

INSTITUCIÓN / INSTITUTION:  - Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: gozaloa@niaid.nih.gov.

RESUMEN / SUMMARY:  - Pulmonary thromboembolism associated with pancreatic endocrine neoplasia is extremely uncommon in man and animals. Post-mortem examination of an adult owl monkey (Aotus nancymae) revealed extensive pulmonary arterial thromboembolism and a well-demarcated mass attached to the pancreas. Microscopically, the mass consisted of areas of interstitial fibrosis with loss of acini and islets and replacement by nests and sheets of polygonal cells with amphophilic cytoplasm, an eccentric round nucleus with stippled chromatin and, in some cells, with a single prominent eccentric nucleolus. Clusters of these cells were noted within vessels  and adjacent lymph nodes. The cells did not express S100 or insulin, but were labelled strongly with SP-1/chromogranin. Rare individual cells expressed glucagon and somatostatin. A few cells in pulmonary thrombi/emboli and the adjacent lymph node also expressed SP-1/chromogranin. Based on cell morphology, location and immunohistochemistry the tumour was classified as pancreatic endocrine (islet cell) carcinoma with metastasis to regional lymph nodes and lung.

 

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[167]

TÍTULO / TITLE:  - A minimally invasive and simple screening test for detection of pancreatic ductal adenocarcinoma using biomarkers in duodenal juice.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar;42(2):187-92. doi: 10.1097/MPA.0b013e3182649979.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e3182649979

AUTORES / AUTHORS:  - Mori Y; Ohtsuka T; Kono H; Nagayoshi Y; Ideno N; Aso T; Kozono S; Ohuchida K; Takahata S; Nakamura M; Mizumoto K; Tanaka M

INSTITUCIÓN / INSTITUTION:  - From the Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

RESUMEN / SUMMARY:  - OBJECTIVES: The aim of this study was to establish a minimally invasive and simple screening test for detection of pancreatic ductal adenocarcinoma (PDAC) using duodenal juice (DJ). METHODS: Duodenal juice was collected prospectively before endoscopic retrograde cholangiopancreatography in 46 patients. A protease  inhibitor was not added to the samples collected during the initial 2.5 minutes but was added in the latter 2.5 minutes. Thereafter, secretin was administered intravenously, and DJ was subsequently collected for additional 10 minutes. The sensitivities of carcinoembryonic antigen (CEA), S100 calcium-binding protein P (S100P), and interleukin 8 in DJ and pancreatic juice were assessed. RESULTS: There were 30 patients with PDAC and 16 with benign lesions. It was possible to collect an adequate amount of DJ without secretin administration. In the PDAC group, CEA concentrations in DJ were significantly higher than those in the benign group, even without the use of a protease inhibitor. S100P levels in DJ in the PDAC group were significantly higher than those in the benign group in the presence of the protease inhibitor. CONCLUSIONS: Duodenal juice collection during routine upper endoscopy and assessments of CEA and S100P in DJ might become a useful screening test for detection of PDAC.

 

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[168]

TÍTULO / TITLE:  - Intraductal Papillary Mucinous Neoplasm Associated With Autoimmune Pancreatitis.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Apr;42(3):552-554.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826cc2fc

AUTORES / AUTHORS:  - Naitoh I; Nakazawa T; Notohara K; Miyabe K; Hayashi K; Shimizu S; Kondo H; Yoshida M; Yamashita H; Umemura S; Ohara H; Joh T

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences Nagoya, Japan tnakazaw@med.nagoya-cu.ac.jp Department  of Pathology Kurashiki Central Hospital Kurashiki, Japan Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences Nagoya, Japan Department of Community-based Medical Education Nagoya City University Graduate School of Medical Sciences Nagoya, Japan Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences Nagoya, Japan.

 

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[169]

TÍTULO / TITLE:  - Branch duct intraductal papillary mucinous neoplasms of the pancreas: watch and wait is not harmless.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar;42(2):358. doi: 10.1097/MPA.0b013e31826ae338.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826ae338

AUTORES / AUTHORS:  - Fritz S; Werner J; Buchler MW

INSTITUCIÓN / INSTITUTION:  - Department of General and Visceral Surgery University of Heidelberg Heidelberg, Germany Markus.Buechler@med.uni-heidelberg.de.

 

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[170]

TÍTULO / TITLE:  - Metformin Inhibits the Growth of Human Pancreatic Cancer Xenografts.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31827aec40

AUTORES / AUTHORS:  - Kisfalvi K; Moro A; Sinnett-Smith J; Eibl G; Rozengurt E

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Medicine, daggerSurgery, and double daggerCURE: Digestive Diseases Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA.

RESUMEN / SUMMARY:  - OBJECTIVE: Pancreatic ductal adenocarcinoma is a devastating disease, with an overall 5-year survival rate of only 3% to 5%. As the current therapies offer very limited survival benefits, novel therapeutic strategies are urgently required to treat this disease. Here, we determined whether metformin administration inhibits the growth of PANC-1 and MiaPaCa-2 tumor xenografts in vivo. METHODS: Different xenograft models, including orthotopic implantation, were used to determine whether intraperitoneal or oral administration of metformin inhibits the growth of pancreatic cancer in vivo. RESULTS: We demonstrate that metformin given once daily intraperitoneally at various doses (50-250 mg/kg) to nude mice inhibited the growth of PANC-1 xenografts in a dose-dependent manner. A significant effect of metformin was obtained at 50 mg/kg and maximal effect at 200 mg/kg. Metformin administration also caused a significant reduction in the phosphorylation of ribosomal S6 protein and ERK in these xenografts. Metformin also inhibited the growth of pancreatic cancer xenografts when administered orally (2.5 mg/mL) either before or after tumor implantation. Importantly, oral administration of metformin also inhibited the growth of MiaPaCa-2 tumors xenografted orthotopically. CONCLUSIONS: The studies presented here provide further evidence indicating that metformin offers a potential novel approach for pancreatic ductal adenocarcinoma prevention and therapy.

 

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[171]

TÍTULO / TITLE:  - Complete Pathological Remission of Locally Advanced, Unresectable Pancreatic Cancer (LAPC) after Intensified Neoadjuvant Chemotherapy.

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

REVISTA / JOURNAL:  - Onkologie. 2013;36(3):123-5. doi: 10.1159/000348527. Epub 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000348527

AUTORES / AUTHORS:  - Hartlapp I; Muller J; Kenn W; Steger U; Isbert C; Scheurlen M; Germer CT; Einsele H; Kunzmann V

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine II, University of Wurzburg, Germany.

RESUMEN / SUMMARY:  - Background: Unresectable locally advanced pancreatic cancer (LAPC) has an extremely poor prognosis. Results of neoadjuvant (radio-)chemotherapy approaches  aiming at achieving resectability are currently not satisfactory. Case Report: We report the case of a 67-year-old woman with histologically confirmed pancreas carcinoma that was not resectable on first surgical exploration who achieved a well-documented complete pathological remission (pCR). The carcinoma became resectable after consecutive neoadjuvant treatment with nanoparticle albumin-bound (nab)-paclitaxel/gemcitabine and FOLFIRINOX chemotherapy regimens.  Conclusion: This is the first reported LAPC case in which neoadjuvant chemotherapy alone has been shown to lead to demonstrated pCR. CA19-9 levels, but not imaging criteria, were useful for response prediction and timing of the Whipple’s procedure. The findings in this case suggest possible conceptual changes in the treatment approach for LAPC, and indicate that the new effective chemotherapy regimens should be integrated into clinical trials for LAPC.

 

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[172]

TÍTULO / TITLE:  - Adenosquamous carcinoma of the pancreas: multidetector-row computed tomographic manifestations and tumor characteristics.

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

REVISTA / JOURNAL:  - J Comput Assist Tomogr. 2013 Mar;37(2):125-33. doi: 10.1097/RCT.0b013e31827bc452.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RCT.0b013e31827bc452

AUTORES / AUTHORS:  - Yin Q; Wang C; Wu Z; Wang M; Cheng K; Zhao X; Yuan F; Tang Y; Miao F

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Radiology, daggerGeneral Surgery, and double daggerPathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

RESUMEN / SUMMARY:  - OBJECTIVE: The purpose of this article was to present the adenosquamous carcinoma (ASqC) of the pancreas: multidetector-row computed tomographic (CT) features and  tumor characteristics. MATERIALS AND METHODS: The clinical data and CT studies of 12 patients with pathologically proven ASqC of the pancreas between the dates February 2001 and February 2010 were retrospectively analyzed. RESULTS: The presenting symptoms of ASqC of the pancreas were nonspecific. Elevated serum levels of carbohydrate antigen 19-9, carbohydrate antigen 12-5, and carcinoembryonic antigen were noted. The tumor was most commonly involved in the  pancreatic head in 6 patients, with the dilation of the common bile duct and the  upstream main pancreatic duct. All ASqCs exhibited invasive growth. No calcification and intratumoral hemorrhage were noted in ASqCs. Ten tumors showed  enhancement in the early arterial phase and persistent enhancement in the portal  vein phase. CONCLUSION: The typical CT appearance of ASqC was solitary oval or round without any capsule and a defined margin. The dilation of the main pancreatic duct and/or the common bile duct was always discovered. The huge infiltrative lesion outside the pancreas was detected in the tail and/or the body of the pancreas. Not only the elevation of carbohydrate antigen 19-9 is common, but also Ca12-5 and CEA, whereas human alpha fetoprotein elevation is not observed. The enhancement pattern of tumor showed persistence in the portal vein  phase.

 

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[173]

TÍTULO / TITLE:  - Hepatobiliary and Pancreatic: Cystic bile duct remnant after surgery for a choledochal cyst.

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

REVISTA / JOURNAL:  - J Gastroenterol Hepatol. 2013 Apr;28(4):754. doi: 10.1111/jgh.12126.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jgh.12126

AUTORES / AUTHORS:  - Matsuura K; Hashimoto D; Ikuta Y; Chikamoto A; Beppu T; Baba H

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.

 

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[174]

TÍTULO / TITLE:  - VEGF-C ShRNA inhibits pancreatic cancer growth and lymphangiogenesis in an orthotopic fluorescent nude mouse model.

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Feb;33(2):409-17.

AUTORES / AUTHORS:  - Shi Y; Tong M; Wu Y; Yang Z; Hoffman RM; Zhang Y; Tian Y; Qi M; Lin Y; Liu Y; Dai L; Sun Y; Wang Z

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, East Hospital, Tongji University School of Medicine. 150 Jimo Road, Shanghai 200120, PR China.

RESUMEN / SUMMARY:  - The aim of this study was to assess the inhibitory efficacy of short hairpin RNA  (ShRNA) targeting vascular endothelial growth factor C (VEGF-C) in an orthotopic  pancreatic cancer mouse model. BxPC-3 human pancreatic cancer cells expressing green fluorescent protein (GFP) were orthotopically implanted onto the pancreas of nude mice. All mice were randomly divided into four groups when the average tumor size had reached 100 mm(3) and were treated with either vehicle or gemcitabine at 150 mg/kg; or intravenous VEGF-C ShRNA at 150 mg/kg; or intratumoral VEGF-C ShRNA at 150 mug/kg. In vivo fluorescence imaging was performed to monitor tumor growth and metastasis during the study. Real-time quantitative polymerase chain reaction (RT-qPCR) and an enzyme-linked immunosorbent assay (ELISA) were performed to determine the mRNA and protein level of VEGF-C in tumor tissues. Lymphatic vessel marker D2-40, blood vessel marker CD31 and proliferation marker Ki67 expression of the tumor tissues were analyzed by immunohistochemistry staining. Intravenous and intratumoral VEGF-C ShRNA treatment significantly inhibited tumor growth, downregulated the expression of VEGF-C mRNA, reduced tumor microlymphatic vessel density (MLVD), and inhibited cancer cell proliferation. Gemcitabine, as the standard treatment for pancreatic cancer, demonstrated a stronger inhibitory effect on tumor growth, with less inhibition of MLVD and more inhibition of microvessel density (MVD) and proliferation than VEGF-C ShRNA. These results indicate that different mechanisms are associated with the efficacy of gemcitabine and VEGF-C ShRNA.

 

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[175]

TÍTULO / TITLE:  - Diabetes, insulin use, smoking, and pancreatic cancer mortality in Taiwan.

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

REVISTA / JOURNAL:  - Acta Diabetol. 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00592-013-0471-0

AUTORES / AUTHORS:  - Tseng CH

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, National Taiwan University College of Medicine,  No. 7 Chung-Shan South Road, Taipei, 100, Taiwan, ccktsh@ms6.hinet.net.

RESUMEN / SUMMARY:  - The aim of the study was to evaluate the link between diabetes and pancreatic cancer (PC) mortality and the joint effect of smoking and insulin use on PC mortality. A total of 39,988 men and 46,909 women with type 2 diabetes, aged >/=25 years and recruited in 1995-1998, were followed to 2006 for PC mortality. Age-sex-specific mortality rate ratios for diabetic patients versus the general population were calculated. Cox regression was used to evaluate hazard ratios for PC mortality for covariates including age, sex, diabetes duration, body mass index, smoking, insulin use, and area of residence. The interaction and joint effect of smoking and insulin use were also evaluated. A total of 89 men and 63 women died of PC. The mortality rate ratios (95 % CI) showed a significantly higher risk in diabetic patients with a magnitude most remarkable at the youngest age: 1.51 (1.15, 1.98), 2.02 (1.35, 3.03), and 8.36 (5.39, 12.98) for >/=65, 55-64, and 25-54 years old, respectively, for men; and 1.16 (0.84, 1.59), 2.12 (1.39, 3.23) and 3.33 (1.14, 9.68), respectively, for women. In multivariable Cox regression analysis, only age was significantly predictive for PC mortality. Although smoking and insulin use might be associated with a 50 % higher risk when analyzed as individual risk factors, they did not reach statistical significance. The interaction term of smoking and insulin use was also not statistically significant in additional modeling. However, smoking and insulin use jointly increased the risk with an adjusted hazard ratio (95 % CI) of 3.04 (1.37, 6.73) when compared to patients who did not smoke and did not use insulin. Diabetic patients have a significantly higher risk of PC mortality. In patients with type  2 diabetes, smoking and insulin use may jointly increase the risk by threefold.

 

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[176]

TÍTULO / TITLE:  - BCL10 as a useful marker for pancreatic acinar cell carcinoma, especially using endoscopic ultrasound cytology specimens.

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

REVISTA / JOURNAL:  - Pathol Int. 2013 Mar;63(3):176-82. doi: 10.1111/pin.12045.

            ●● Enlace al texto completo (gratuito o de pago) 1111/pin.12045

AUTORES / AUTHORS:  - Hosoda W; Sasaki E; Murakami Y; Yamao K; Shimizu Y; Yatabe Y

INSTITUCIÓN / INSTITUTION:  - Departments of Pathology and Molecular Diagnostics.

RESUMEN / SUMMARY:  - Acinar cell carcinomas (ACCs) of the pancreas are characterized by the histological and immunohistochemical features of acinar cell differentiation. Recently, BCL10, originally identified as a recurrent t(1;14)(p22;q32) translocation in MALT B-cell lymphoma, was found to be immunohistochemically positive in some solid tumors, including ACC. To evaluate its diagnostic efficacy, we performed BCL10 immunohistochemistry and evaluated molecular markers correlated to pancreatic tumor lineages (neuroendocrine markers and a mutation analysis of KRAS and GNAS) using samples from 126 pancreatic tumors (17 ACCs, 24  pancreatic ductal adenocarcinomas, 4 adenosquamous carcinomas, 9 intraductal papillary mucinous neoplasms, 10 mucinous cystic neoplasms, 44 neuroendocrine tumors, 9 serous cystic tumors and 10 solid-pseudopapillary neoplasms). BCL10 was exclusively expressed in normal acini. In pancreatic tumors, 14 of 17 (82%) ACCs  and 2 of 4 (50%) adenosquamous carcinomas were positive, while the other subtypes were almost negative. We subsequently examined the diagnostic utility of BCL10 in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens using 57  pancreatic tumors. BLC10 correctly identified ACCs (9/13) and adenosquamous carcinomas (2/4) but none of the other subtypes (n = 41). Therefore, we suggested that BCL10 expression is a useful marker for acinar cell differentiation, particularly in the diagnosis of EUS-FNA specimens.

 

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[177]

TÍTULO / TITLE:  - Invaginated ampulla of Vater in synchronous malignant intraductal papillary mucinous neoplasm of the pancreas and common bile duct cancer.

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

REVISTA / JOURNAL:  - Endoscopy. 2013;45 Suppl 2 UCTN:E25-6. doi: 10.1055/s-0032-1326106. Epub 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1326106

AUTORES / AUTHORS:  - Han JW; Jang SI; Ma DW; Yoon SO; Lee DK

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

 

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[178]

TÍTULO / TITLE:  - A Case of Insulinoma Detected by 68Ga-DOTANOC PET/CT and Missed by 18F-Dihydroxyphenylalanine PET/CT.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31825b222f

AUTORES / AUTHORS:  - Treglia G; Inzani F; Campanini N; Rindi G; Agnes S; Giordano A; Rufini V

INSTITUCIÓN / INSTITUTION:  - From the *Institute of Nuclear Medicine, Department of Bioimaging and Radiological Sciences and daggerInstitute of Pathology, Catholic University of the Sacred Heart, Rome; double daggerDepartment of Pathology and Laboratory Medicine, University of Parma, Parma; and section signDepartment of Surgery, Catholic University of the Sacred Heart, Rome, Italy.

RESUMEN / SUMMARY:  - ABSTRACT: A 65-year-old woman with suspected insulinoma on the basis of clinical, biochemical, and conventional imaging data underwent F-dihydroxyphenylalanine (DOPA) PET/CT and Ga-DOTANOC PET/CT. F-DOPA PET/CT did not show any focal uptake  in the pancreas, whereas Ga-DOTANOC PET/CT showed a focal area of intense uptake  in the pancreatic tail. The patient underwent surgery and an insulinoma of about  20 mm in diameter was detected in the pancreatic tail. F-DOPA PET may fail in localizing insulin secreting tumors in adults; in these cases, the use of Ga-somatostatin analogs may lead to the correct diagnosis.

 

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[179]

TÍTULO / TITLE:  - A Rare Case of Ectopic Adrenocorticotropic Hormone Syndrome Caused by a Metastatic Neuroendocrine Tumor of the Pancreas Detected by 68Ga-DOTANOC and 18F-FDG PET/CT.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318279ec68

AUTORES / AUTHORS:  - Treglia G; Salomone E; Petrone G; Giaccari A; Rindi G; Rufini V

INSTITUCIÓN / INSTITUTION:  - From the *Institute of Nuclear Medicine, Department of Bioimaging and Radiological Sciences, daggerDivision of Endocrinology and Metabolic Diseases, and double daggerInstitute of Pathology, Catholic University of the Sacred Heart, Rome, Italy.

RESUMEN / SUMMARY:  - We report a rare case of ectopic adrenocorticotropic hormone (ACTH) syndrome caused by a metastatic neuroendocrine tumor (NET) of the pancreas detected by PET/CT using different tracers. A 43-year-old female patient with Cushing syndrome (CS) by suspected ectopic ACTH secretion underwent a Ga-DOTANOC and a F-FDG PET/CT. Both these functional imaging techniques revealed increased tracer  uptake in a pancreatic mass and multiple liver metastases. Histology showed the presence of a mildly differentiated pancreatic NET. Ga-DOTANOC PET/CT may be a useful functional imaging method, complementary to F-FDG PET/CT, in detecting ACTH-secreting pancreatic NETs.

 

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[180]

TÍTULO / TITLE:  - Diagnosis and management of insulinoma.

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

REVISTA / JOURNAL:  - World J Gastroenterol. 2013 Feb 14;19(6):829-37. doi: 10.3748/wjg.v19.i6.829.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i6.829

AUTORES / AUTHORS:  - Okabayashi T; Shima Y; Sumiyoshi T; Kozuki A; Ito S; Ogawa Y; Kobayashi M; Hanazaki K

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Kochi Health Sciences Center, Kochi 781-8555, Japan. takehiro_okabayashi@khsc.or.jp

RESUMEN / SUMMARY:  - Insulinomas, the most common cause of hypoglycemia related to endogenous hyperinsulinism, occur in 1-4 people per million of the general population. Common autonomic symptoms of insulinoma include diaphroresis, tremor, and palpitations, whereas neuroglycopenenic symptoms include confusion, behavioural changes, personality changes, visual disturbances, seizure, and coma. Diagnosis of suspected cases is based on standard endocrine tests, especially the prolonged fasting test. Non-invasive imaging procedures, such as computed tomography and magnetic resonance imaging, are used when a diagnosis of insulinoma has been made to localize the source of pathological insulin secretion. Invasive modalities, such as endoscopic ultrasonography and arterial stimulation venous sampling, are  highly accurate in the preoperative localization of insulinomas and have frequently been shown to be superior to non-invasive localization techniques. The range of techniques available for the localization of insulinomas means that blind resection can be avoided. Intraoperative manual palpation of the pancreas by an experienced surgeon and intraoperative ultrasonography are both sensitive methods with which to finalize the location of insulinomas. A high proportion of  patients with insulinomas can be cured with surgery. In patients with malignant insulinomas, an aggressive medical approach, including extended pancreatic resection, liver resection, liver transplantation, chemoembolization, or radiofrequency ablation, is recommended to improve both survival and quality of life. In patients with unresectable or uncontrollable insulinomas, such as malignant insulinoma of the pancreas, several techniques should be considered, including administration of ocreotide and/or continuous glucose monitoring, to prevent hypoglycemic episodes and to improve quality of life.

 

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[181]

TÍTULO / TITLE:  - EUS for Pancreas Cysts: What Should We Be Sampling?

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

REVISTA / JOURNAL:  - Dig Dis Sci. 2013 Mar 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10620-013-2617-x

AUTORES / AUTHORS:  - Sreenarasimhaiah J

INSTITUCIÓN / INSTITUTION:  - University of Texas Southwestern Medical Center, Dallas, TX, USA, jayaprakash.sree@yahoo.com.

 

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[182]

TÍTULO / TITLE:  - Tumor-positive resection margins reflect an aggressive tumor biology in pancreatic cancer.

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

REVISTA / JOURNAL:  - J Surg Oncol. 2013 Feb 28. doi: 10.1002/jso.23299.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jso.23299

AUTORES / AUTHORS:  - Kimbrough CW; St Hill CR; Martin RC; McMasters KM; Scoggins CR

INSTITUCIÓN / INSTITUTION:  - Division of Surgical Oncology, The Hiram C. Polk, J.R., M.D. Department of Surgery, University of Louisville, Louisville, Kentucky.

RESUMEN / SUMMARY:  - BACKGROUND: Resection margin status has been shown to impact outcomes for pancreatic adenocarcinoma (PAC), yet it remains unknown whether margin status is  a reflection of tumor biology or surgical technique. METHODS: Two hundred eighty-three consecutive patients with pancreatic adenocarcinoma were identified  in a prospectively maintained database. Only patients with R0 (n = 207) or R1 (n  = 76) tumors were included. Each operative surgeon’s first 50 cases were excluded to control for technical inexperience. Univariable and multivariable analyses of  clinicopathologic and intra-operative factors were performed. RESULTS: The median follow-up for the cohort was 30.3 months with a median overall survival (OS) of 19.0 months. The R1 group had a higher rate of lymph node ratio >0.2 (41% vs. 25%; P = 0.013), and more microvascular invasion (64% vs. 44%; P = 0.007). R0 resections had both improved overall survival (22.7 months vs. 15.0 months, P = 0.004) and disease free survival (13.5 months vs. 10.7 months, P = 0.026). Factors independently associated with overall survival were microvascular invasion (HR 2.26; P = 0.001), pre-existing pulmonary disease (HR 2.18, P = 0.043), and cardiac disease (HR 1.78, P = 0.033). CONCLUSION: Factors associated  with an R1 resection reflect a biologically more aggressive tumor, with a higher  likelihood of microvascular invasion and increased positive lymph node ratio. J.  Surg. Oncol © 2013 Wiley Periodicals, Inc.

 

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[183]

TÍTULO / TITLE:  - Psammoma bodies and abundant stromal amyloid in an endoscopic ultrasound guided fine needle aspirate (EUS-FNA) of a pancreatic neuroendocrine tumor: A potential  pitfall.

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

REVISTA / JOURNAL:  - Diagn Cytopathol. 2013 Feb 28. doi: 10.1002/dc.22975.

            ●● Enlace al texto completo (gratuito o de pago) 1002/dc.22975

AUTORES / AUTHORS:  - Samad A; Attam R; Jessurun J; Pambuccian SE

INSTITUCIÓN / INSTITUTION:  - Department of Laboratory Medicine and Pathology, and Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.

 

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[184]

TÍTULO / TITLE:  - Hepatobiliary and Pancreatic: Intrahepatic biliary cystadenocarcinoma.

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

REVISTA / JOURNAL:  - J Gastroenterol Hepatol. 2013 Apr;28(4):753. doi: 10.1111/jgh.12127.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jgh.12127

AUTORES / AUTHORS:  - Okano K; Oshima M; Yamamoto N; Yachida S; Suzuki Y

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.

 

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[185]

TÍTULO / TITLE:  - Contemporary management of perihilar cholangiocarcinoma in a nontransplant hepatopancreatobiliary center.

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

REVISTA / JOURNAL:  - Eur J Gastroenterol Hepatol. 2013 Mar 5.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MEG.0b013e32835fba3a

AUTORES / AUTHORS:  - Jegatheeswaran S; Sheen AJ; Siriwardena AK

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Regional Hepatopancreatobiliary Surgery Unit, Manchester Royal Infirmary, Manchester, UK.

RESUMEN / SUMMARY:  - BACKGROUND: Perihilar cholangiocarcinoma (PHCC) is a rare tumor with a poor prognosis. Outcomes may be optimized by centralization. Recent trends suggest further improvement by localization to transplant centers. This study examines outcomes from the management of PHCC in a nontransplant hepatopancreatobiliary center. METHODS: Data were collected prospectively from patients undergoing treatment for PHCC from October 1999 to May 2011. Twenty-four patients underwent  surgery. A further 54 patients had inoperable PHCC. Outcome data are reported. RESULTS: Twenty-two of 24 patients required liver resection with histological R0  status in 12 (50%). In-hospital mortality occurred in two (8%). The mean survival of patients undergoing resection was 39 (95% CI: 16-61) months. The mean survival of nonresected patients was 5 (95% CI: 3-7) months (P<0.0001; log-rank; Mantel-Cox test). CONCLUSION: Currently acceptable standards of holistic care for patients with PHCC can be provided in a nontransplant regional hepatopancreatobiliary center. Further centralization may improve resection volumes and allow more patients to benefit from extended liver resection techniques.

 

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[186]

TÍTULO / TITLE:  - Concentrations and activities of metalloproteinases 2 and 9 and their inhibitors  (TIMPS) in chronic pancreatitis and pancreatic adenocarcinoma.

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

REVISTA / JOURNAL:  - J Physiol Pharmacol. 2012 Dec;63(6):589-99.

AUTORES / AUTHORS:  - Lekstan A; Lampe P; Lewin-Kowalik J; Olakowski M; Jablonska B; Labuzek K; Jedrzejowska-Szypulka H; Olakowska E; Gorka D; Filip I; Dranka-Bojarowska D

INSTITUCIÓN / INSTITUTION:  - Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice,  Poland. andrzejlekstan@gmail.com

RESUMEN / SUMMARY:  - Pancreatic cancer (PC) and chronic pancreatitis (CP) are still significant problems. The aim of this study was a comparative analysis of the activity and concentrations of matrix metalloproteinases 2 and 9 and the concentrations of their tissue inhibitors (TIMP 1 and 2) in the PC compared to CP tissue homogenates. The study was performed in a group of 63 patients with pancreatic cancer or chronic pancreatitis selected for resection procedures. Group 1 consisted of 31 patients with CP, group 2 consisted of 32 patients with PC. There was no coincidence of pancreatic cancer in CP group. The pancreatic tumor samples have been properly prepared in order to perform electrophoresis and immunoassay testing. The activity of MMPs and the concentrations of MMPs and TIMPs were evaluated. Results: the revealed activities of gelatinases and concentrations levels of the gelatinases and their inhibitors were significantly higher in the PC tissue samples compared to CP. In both groups, higher concentrations of MMP9 compared to MMP2 and TIMP2 compared to TIMP1 were shown. High potential for tumor invasiveness demonstrated by the formation of lymph node metastases was characterized by the higher concentrations of MMP9 and TIMP2. However, in the case of infiltration of the nerve fibers, a decrease in the concentration of MMP2 was found. Conclusions: gelatinases and their inhibitors play important role in the pathogenesis of the CP as well as PC. The activity and concentration of gelatinases and the concentration of their inhibitors were all significantly higher in the PC group.

 

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[187]

TÍTULO / TITLE:  - Intraductal growing acinar cell carcinoma of the pancreas.

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

REVISTA / JOURNAL:  - Abdom Imaging. 2013 Mar 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00261-013-9993-8

AUTORES / AUTHORS:  - Kim HJ; Kim YK; Jang KT; Lim JH

INSTITUCIÓN / INSTITUTION:  - Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul, 135-710, Korea.

RESUMEN / SUMMARY:  - Acinar cell carcinoma (ACC) is a rare pancreatic exocrine neoplasm characterized  by a huge, exophytic well-circumscribed hypovascular mass. There has been several reports describing intraductal and papillary variant of ACC and they showed different radiologic features from usual ACC. We present histologically confirmed cases of intraductal and papillary variant of ACC that had been found in two patients, who underwent CT and MRI. This report provides CT and MRI features of intraductal and papillary variant of ACC in pancreas with pathologic correlation  after surgical excision.

 

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[188]

TÍTULO / TITLE:  - Hypocellular pancreatic cyst aspirates—what are we missing?

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

REVISTA / JOURNAL:  - Diagn Cytopathol. 2013 Mar;41(3):189-91. doi: 10.1002/dc.21797. Epub 2011 Aug 26.

            ●● Enlace al texto completo (gratuito o de pago) 1002/dc.21797

AUTORES / AUTHORS:  - Kapur U; Staerkel GA

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Loyola University Medical Center, Maywood, Illinois 60153, USA. ukapur@lumc.edu

 

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[189]

TÍTULO / TITLE:  - Inflammatory networks and immune surveillance of pancreatic carcinoma.

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

REVISTA / JOURNAL:  - Curr Opin Immunol. 2013 Feb 16. pii: S0952-7915(13)00007-1. doi: 10.1016/j.coi.2013.01.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.coi.2013.01.006

AUTORES / AUTHORS:  - Vonderheide RH; Bayne LJ

INSTITUCIÓN / INSTITUTION:  - 8-121 Smilow Center for Translational Research, 3400 Civic Center Blvd, Abramson  Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: rhv@exchange.upenn.edu.

RESUMEN / SUMMARY:  - Cancer-associated inflammation plays an important role in restraining anti-tumor  immunity, particularly in pancreatic ductal adenocarcinoma (PDA) for which a massive infiltration of immunosuppressive leukocytes into the tumor stroma is an  early and consistent event in oncogenesis. Intratumoral effector T cells are rare. This pathophysiology is in contrast to many other solid tumors for which infiltration of effector T cells is often prominent, associated with improved clinical outcomes, and mechanistically contributes to tumor immunoediting that ultimately can mediate immune escape. In PDA, increasing evidence suggests that the ras oncogene drives an inflammatory program that establishes immune privilege in the tumor microenvironment. Indeed, PDA cells might remain intrinsically sensitive to T cell killing because they have never been exposed to T cell selective pressure in vivo. In support of this hypothesis, recent studies demonstrate that derailing immune suppressive pathways in the PDA microenvironment, such as tumor derived GM-CSF, facilitates T-cell mediated tumor rejection. These findings carry major implications for the development of novel,  combination immunotherapies for pancreatic cancer.

 

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[190]

TÍTULO / TITLE:  - Metachronous colonic metastasis from pancreatic cancer seven years post-pancreatoduodenectomy.

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

REVISTA / JOURNAL:  - World J Gastroenterol. 2013 Mar 14;19(10):1665-8. doi: 10.3748/wjg.v19.i10.1665.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i10.1665

AUTORES / AUTHORS:  - Inada K; Shida D; Noda K; Inoue S; Warabi M; Umekita N

INSTITUCIÓN / INSTITUTION:  - Kentaro Inada, Dai Shida, Kazumasa Noda, Satoru Inoue, Nobutaka Umekita, Department of Surgery, Tokyo Metropolitan Bokutoh Hospital, Sumida-ku, Tokyo 1308575, Japan.

RESUMEN / SUMMARY:  - Colonic metastasis from other organs is very rare. Here we report the case of a 62-year-old man with a history of pancreatoduodenectomy for stage IIB pancreatic  head cancer performed seven years back. He presented with abdominal distension and pain. Under the preoperative diagnosis of bowel obstruction, surgical treatment was performed, and a circumferential lesion causing bowel obstruction of the ascending colon was detected. A right hemicolectomy with lymph node dissection was performed. The specimen showed a 5-cm wall thickening with a cobble-stone like appearance of the ascending colon, which morphologically appeared scirrhous. Histological examination revealed cancer nests invading from  the subserosa to the muscular and submucosal layers of the colon. Immunohistochemical analysis of the tumor cells demonstrated positive staining for cytokeratin 7, but negative for cytokeratin 20, which was the same as the previous pancreatic cancer specimen. These pathological and immunohistochemical features strongly supported the diagnosis of colonic metastasis from the pancreas. Thereafter, the patient received systemic chemotherapy, but unfortunately, he died 14 mo after the surgery.

 

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[191]

TÍTULO / TITLE:  - Middle segmental pancreatectomy: A safe and organ-preserving option for benign and low-grade malignant lesions.

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

REVISTA / JOURNAL:  - World J Gastroenterol. 2013 Mar 7;19(9):1458-65. doi: 10.3748/wjg.v19.i9.1458.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i9.1458

AUTORES / AUTHORS:  - Du ZY; Chen S; Han BS; Shen BY; Liu YB; Peng CH

INSTITUCIÓN / INSTITUTION:  - Zhi-Yong Du, Ying-Bing Liu, Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.

RESUMEN / SUMMARY:  - AIM: To study the feasibility and safety of middle segmental pancreatectomy (MSP) compared with pancreaticoduodenectomy (PD) and extended distal pancreatectomy (EDP). METHODS: We studied retrospectively 36 cases that underwent MSP, 44 patients who underwent PD, and 26 who underwent EDP with benign or low-grade malignant lesions in the mid-portion of the pancreas, between April 2003 and December 2009 in Ruijin Hospital. The perioperative outcomes and long-term outcomes of MSP were compared with those of EDP and PD. Perioperative outcomes included operative time, intraoperative hemorrhage, transfusion, pancreatic fistula, intra-abdominal abscess/infection, postoperative bleeding, reoperation,  mortality, and postoperative hospital time. Long-term outcomes, including tumor recurrence, new-onset diabetes mellitus (DM), and pancreatic exocrine insufficiency, were evaluated. RESULTS: Intraoperative hemorrhage was 316.1 +/- 309.6, 852.2 +/- 877.8 and 526.9 +/- 414.5 mL for the MSP, PD and EDP groups, respectively (P < 0.05). The mean postoperative daily fasting blood glucose level was significantly lower in the MSP group than in the EDP group (6.3 +/- 1.5 mmol/L vs 7.3 +/- 1.5 mmol/L, P < 0.05). The rate of pancreatic fistula was higher in the MSP group than in the PD group (42% vs 20.5%, P = 0.039), all of the fistulas after MSP corresponded to grade A (9/15) or B (6/15) and were sealed following conservative treatment. There was no significant difference in the mean postoperative hospital stay between the MSP group and the other two groups. After a mean follow-up of 44 mo, no tumor recurrences were found, only one patient (2.8%) in the MSP group vs five (21.7%) in the EDP group developed new-onset insulin-dependent DM postoperatively (P = 0.029). Moreover, significantly fewer patients in the MSP group than in the PD (0% vs 33.3%, P < 0.001) and EDP (0% vs  21.7%, P = 0.007) required enzyme substitution. CONCLUSION: MSP is a safe and organ-preserving option for benign or low-grade malignant lesions in the neck and proximal body of the pancreas.

 

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[192]

TÍTULO / TITLE:  - Limited Efficacy of 18F-FDG PET/CT for Differentiation Between Metastasis-Free Pancreatic Cancer and Mass-Forming Pancreatitis.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182817d9d

AUTORES / AUTHORS:  - Kato K; Nihashi T; Ikeda M; Abe S; Iwano S; Itoh S; Shimamoto K; Naganawa S

INSTITUCIÓN / INSTITUTION:  - From the *Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine; daggerDepartment of Radiology, Nagoya University Hospital; double daggerDepartment of Radiology, Nagoya University Graduate School of Medicine; and section signDepartment of Radiology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.

RESUMEN / SUMMARY:  - OBJECTIVE: Differentiation between metastasis-free pancreatic cancer and mass-forming pancreatitis is important to avoid unnecessary operative procedures. This study was aimed at evaluating the efficacy of PET/CT with F-FDG (FDG PET/CT) for the differential diagnosis between them. PATIENTS AND METHODS: FDG-PET/CT was performed in 47 study patients with pancreatic masses and without any detectable  metastases, 33 of which cases were finally diagnosed as pancreatic cancer and the other 14 as pancreatitis, and the corresponding imaging data were evaluated retrospectively. The maximal SUV (SUVmax) within the masses were determined at 1  hour and mostly at 2 hours after intravenous injection of FDG. RESULTS: SUVmax at 1 hour in pancreatic cancer was significantly higher than that in mass-forming pancreatitis, and the change in SUVmax from 1- to 2-hour time points was more consistent with pancreatic cancer than with mass-forming pancreatitis. However, there remained considerable overlapping between the SUVmax values of both diseases except either at the higher range for pancreatic cancer (>7.7 at 1 hour  or >9.98 at 2 hours) or at the lower range for mass-forming pancreatitis (<3.37 at 1 hour or <3.53 at 2 hours). No obvious difference was found in the FDG uptake patterns of the mass areas between both diseases. CONCLUSIONS: Differentiation between metastasis-free pancreatic cancer and mass-forming pancreatitis is difficult by FDG-PET/CT due to considerable overlapping between the SUVmax values of the two diseases, although the differential diagnosis may be possible either at the higher range of SUVmax (> 7.7 at 1 hour or >9.98 at 2 hours) for pancreatic cancer or at the lower range of SUVmax (<3.37 at 1 hour or <3.53 at 2  hours) for mass-forming pancreatitis.

 

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[193]

TÍTULO / TITLE:  - Enhancing sorafenib-mediated sensitization to gemcitabine in Experimental Pancreatic Cancer through EMAP II.

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

REVISTA / JOURNAL:  - J Exp Clin Cancer Res. 2013 Mar 6;32(1):12.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1756-9966-32-12

AUTORES / AUTHORS:  - Awasthi N; Zhang C; Hinz S; Schwarz MA; Schwarz RE

RESUMEN / SUMMARY:  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies and tends to be relatively resistant to conventional therapies. Activated Ras oncogene mutations are found in up to 90% of PDAC, leading to activation of the Ras/Raf/MEK/ERK signaling pathway. Sorafenib is a multikinase inhibitor of the Ras/Raf/MEK/ERK pathway and of tumor angiogenesis. Endothelial monocyte activating polypeptide II (EMAP) enhances gemcitabine effects in PDAC. Antitumor activity of sorafenib was evaluated in combination with gemcitabine (Gem) and the antiangiogenic agent EMAP in experimental PDAC. METHODS: Cell proliferation and protein expression were analyzed by WST-1 assay and Western blotting. Animal survival studies were performed in murine PDAC xenografts. RESULTS: Sorafenib decreased phospho-MEK, phospho-ERK1/2, phospho-p70S6K and phospho-4EBP-1 expression in PDAC cells. Sorafenib inhibited in vitro proliferation of all four PDAC cell lines tested. Additive effects on cell proliferation inhibition were observed in the gemcitabine-sorafenib combination in PDAC cells, and in combinations of sorafenib or EMAP with gemcitabine in endothelial (HUVEC) and fibroblast (WI-38) cells. Sorafenib, alone or in combination with gemcitabine and EMAP, induced apoptosis in HUVECs and WI-38 cells as observed via increased expression of cleaved poly (ADP-ribose) polymerase-1 (PARP-1) and caspase-3 proteins. Compared to controls (median survival: 22 days), animal survival increased after Gem therapy (29 days) but not in sorafenib (23 days) or EMAP therapy alone (both 25 days). Further increases in survival occurred in combination therapy groups Gem+sorafenib (30 days, p=0.004), Gem+EMAP (33 days, p=0.002), and Gem+sorafenib+EMAP (36 days, p=0.004), but not after the sorafenib+EMAP combination (24 days). CONCLUSIONS: These findings demonstrate that the addition of a polymechanistic antiangiogenic agent such as EMAP can enhance the combination treatment effects of sorafenib and cytotoxic PDAC therapy.

 

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[194]

TÍTULO / TITLE:  - Misleading features of neuroimaging and electroencephalography: insulinoma misdiagnosed as temporal lobe epilepsy.

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

REVISTA / JOURNAL:  - Epileptic Disord. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1684/epd.2013.0556

AUTORES / AUTHORS:  - Aupy J; Benoilid A; Sarhan M; Dalvit C; Valenti MP; Hirsch E

INSTITUCIÓN / INSTITUTION:  - Departement de Neurologie, Hopital Universitaire de Strasbourg, Strasbourg, Departement de Neurologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux.

RESUMEN / SUMMARY:  - Epilepsy is a common disorder but diagnosis remains largely clinical. Although MRI and EEG significantly aid the diagnosis of epilepsy, these techniques may also be misleading and indicate abnormalities not related to phenomenology. Consequences of erroneous diagnosis of epilepsy may lead to aggressive and escalating pharmacotherapy with potentially serious side effects. Metabolic disorders, which may mimic epilepsy, should always be considered as they are potentially curable and may be fatal if untreated. We report a case of an insulinoma, misdiagnosed as temporal lobe epilepsy. We highlight the risks associated with misinterpretation of neuroimaging and EEG and outline an approach to differentiate between symptoms of insulinoma or neuroglycopenia and temporal epileptic seizures.

 

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[195]

TÍTULO / TITLE:  - A Patient With Pancreas Divisum, Recurrent Acute Pancreatitis, and Homozygosity for the Cystic Fibrosis Transmembrane Regulator-Associated Protein 5T Allele.

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

REVISTA / JOURNAL:  - Clin Gastroenterol Hepatol. 2013 Feb 13. pii: S1542-3565(13)00189-4. doi: 10.1016/j.cgh.2013.02.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cgh.2013.02.012

AUTORES / AUTHORS:  - Montagnani M; Cazzato S; Mutignani M; Cevenini M; Guidetti E; Zvi IB; Aldini R; Saraceni G; Cavoli C; Garagnani P; Ferrari S; Mantovani V

INSTITUCIÓN / INSTITUTION:  - Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S Orsola-Malpighi-Universita di Bologna, Bologna, Italy; Centro unificato di Ricerca Biomedica Applicata, Policlinico S Orsola-Malpighi-Universita di Bologna, Bologna, Italy. Electronic address: marco.montagnani@unibo.it.

RESUMEN / SUMMARY:  - Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) have been reported to increase the risk of recurrent acute pancreatitis in patients with pancreas divisum. We assessed the CFTR gene in a young male patient with pancreas divisum and recurrent acute pancreatitis. Magnetic resonance cholangiopancreatography and computed tomography revealed that the patient had pancreas divisum, with an enlarged and tortuous pancreatic duct; he also had positive results from the cystic fibrosis sweat test. Genetic analysis did not identify any common CFTR mutations, but did show that he was homozygous for the 5T allele in intron 8 IVS8 5T-12TG (which affects splicing at intron 8). Endoscopic sphincterotomy and stenting of papilla minor was performed. The IVS8 5T-12TG variant has been associated with abnormal organ development, therefore it is possible that CFTR has an important role in the development of the pancreatic  duct. We propose this patient has recurrent acute pancreatitis resulting from a developmental defect associated with a suboptimal CFTR function.

 

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[196]

TÍTULO / TITLE:  - Prediction of invasive candidal infection in critically ill patients with severe  acute pancreatitis.

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

REVISTA / JOURNAL:  - Crit Care. 2013 Mar 18;17(2):R49.

            ●● Enlace al texto completo (gratuito o de pago) 1186/cc12569

AUTORES / AUTHORS:  - Hall A; Poole L; Renton B; Wozniak A; Fisher M; Neal T; Halloran CM; Cox T; Hampshire PA

RESUMEN / SUMMARY:  - INTRODUCTION: Patients with severe acute pancreatitis are at risk of candidal infections carrying the potential risk of an increase in mortality. Since early diagnosis is problematic, several clinical risk scores have been developed to identify patients at risk. Such patients may benefit from prophylactic antifungal therapy while those patients who have a low risk of infection may not benefit and may be harmed. The aim of this study was to assess the validity and discrimination of existing risk scores for invasive candidal infections in patients with severe acute pancreatitis. METHODS: Patients admitted with severe acute pancreatitis to the intensive care unit were analysed. Outcomes and risk factors of admissions with and without candidal infection were compared. Accuracy and discrimination of three existing risk scores for the development of invasive  candidal infection (Candida score, Candida Colonisation Index Score and the Invasive Candidiasis Score) were assessed. RESULTS: 101 patients were identified  from 2003 - 2011. 18 (17.8%) patients developed candidal infection. 30 patients died, giving an overall hospital mortality of 29.7%. Hospital mortality was significantly higher in patients with candidal infection (55.6% compared to 24.1%, p=0.02). Candida colonisation was associated with subsequent candidal infection on multivariate analysis. The Candida Colonisation Index Score was the  most accurate test, with specificity of 0.79 (0.68-0.88), sensitivity of 0.67 (0.41-0.87), negative predictive value of 0.91 (0.82-0.97) and a positive likelihood ratio of 3.2 (1.9-5.5). The Candida Colonisation Index Score showed the best discrimination with area under the receiver operating characteristic curve of 0.79 (0.69-0.87). CONCLUSIONS: In this study the Candida Colonisation Index Score was the most accurate and discriminative test at identifying which patients with severe acute pancreatitis are at risk of developing candidal infection. However its low sensitivity may limit its clinical usefulness.

 

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[197]

TÍTULO / TITLE:  - Frequency and characterization of gastro-entero-pancreatic neuroendocrine tumor patients with high-grade of uptake at somatostatin receptor scintigraphy.

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

REVISTA / JOURNAL:  - Endocr Relat Cancer. 2013 Mar 22;20(2):229-39. doi: 10.1530/ERC-12-0169. Print 2013.

            ●● Enlace al texto completo (gratuito o de pago) 1530/ERC-12-0169

AUTORES / AUTHORS:  - Chougnet CN; Leboulleux S; Caramella C; Lumbroso J; Borget I; Deandreis D; Duvillard P; Elias D; de Baere T; Velayoudom-Cephise FL; Guigay J; Ducreux M; Schlumberger M; Baudin E

INSTITUCIÓN / INSTITUTION:  - Departments of Nuclear Medicine and Endocrine Tumors Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Institut Gustave Roussy, University Paris-Sud, 114 Rue Edouard Vaillant, 94805 Villejuif Cedex, France Department of Endocrinology, University Hospital of Pointe-a-Pitre, Pointe-a-Pitre, Guadeloupe, France Departments of Medical Oncology, Digestive Oncology, Institut Gustave Roussy, University Paris-Sud, 114 Rue Edouard Vaillant, 94805 Villejuif Cedex, France.

RESUMEN / SUMMARY:  - Recent studies suggest that the somatostatin receptor scintigraphy (SRS) grade of uptake is a predictor of response to peptide receptor radionuclide therapy (PRRT). To identify and characterize patients with well-differentiated (WD) neuroendocrine neoplasm (NEN) displaying a high-grade uptake at SRS. Patients with WD-NEN, whose SRS films were available for review, were retrospectively included. SRS was reviewed by three independent readers and classified into four  subgroups based on a modified Krenning’s scale (mKS): no uptake (group-0), homogeneous grade 1-2 uptake (group-1), homogeneous grade 3-4 (group-2), and heterogeneous grade 1-4 (group-3). A simplified scale (sS) of SRS was also used to look for characteristics of patients with high-grade uptake. One hundred and six WD-NEN patients were enrolled. Group-0, group-1, group-2, and group-3 were found in 17, 8, 33, and 42% of cases respectively. High-grade uptake at sS (75% of cases) was correlated with older age, functioning NEN, high chromogranin-A level, and grade 1 (G1) NEN based on mitotic count. Based on the mKS or sS scales, no difference on survival was found. Thirty-three to seventy-five percent of metastatic NEN patients can be considered candidates for PRRT based on homogeneous or heterogeneous high-grade uptake. Functioning G1 NEN patients could be the best candidates for PRRT. Randomized trials are expected to confirm this result.

 

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[198]

TÍTULO / TITLE:  - Efficacy of Everolimus in Patients with Metastatic Insulinoma and Refractory Hypoglycemia.

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

REVISTA / JOURNAL:  - Eur J Endocrinol. 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1530/EJE-12-1101

AUTORES / AUTHORS:  - Bernard V; Lombard-Bohas C; Taquet MC; Caroli-Bosc FX; Ruszniewski P; Niccoli-Sire P; Guimbaud R; Chougnet CN; Goichot B; Rohmer V; Borson-Chazot F; Baudin E

INSTITUCIÓN / INSTITUTION:  - V Bernard, Nuclear Medicine and Endocrine Oncology, Gustave Roussy Institute, Villejuif, 94800, France.

RESUMEN / SUMMARY:  - BACKGROUND: Refractory hypoglycemia in patients with metastatic insulinoma is an  important cause of morbidity and mortality. Everolimus could be a new therapeutic option. METHODS: Within the French Group, we conducted a retrospective, multicentric study of endocrine tumors to evaluate the time to first recurrence of symptomatic hypoglycemia, after everolimus initiation, in patients with metastatic insulinoma and refractory hypoglycemia. Ongoing hyperglycemic medical  options, tumor response, and safety information were recorded. RESULTS: Twelve patients with metastatic insulinoma and refractory hypoglycemia treated with everolimus between May 2007 and June 2011 were reviewed. Everolimus (starting dose, 10 mg/d, except in 1 patient, 5 mg/d) was given after a median of 4 previous therapeutic lines. Clinical benefit was observed in 11 patients, allowing withdrawal of hyperglycemic therapy in 6 patients. After a median duration of 6.5 months (range, 1 to 35+ months), median time to first recurrence  of symptomatic hypoglycemia was 6.5 months (range, 0 to 35+ months). Three patients discontinued everolimus because of cardiac and/or pulmonary adverse events at 1, 1.5, and 7 months after initiation, which led to 2 deaths. Three patients discontinued everolimus because of tumor progression at 2, 3, and 10 months after initiation, without recurrence of hypoglycemia. CONCLUSION: Everolimus appears to be a new effective treatment for patients with metastatic insulinoma and refractory hypoglycemia. Tolerance should be carefully monitored.

 

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[199]

TÍTULO / TITLE:  - CA 19-9 Concentration in Peripheral and Portal Blood of Patients Operated on for  Pancreatic Tumor.

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

REVISTA / JOURNAL:  - Pol Przegl Chir. 2013 Jan 1;85(1):20-8. doi: 10.2478/pjs-2013-0004.

            ●● Enlace al texto completo (gratuito o de pago) 2478/pjs-2013-0004

AUTORES / AUTHORS:  - Szwedziak K; Strzelczyk J

RESUMEN / SUMMARY:  - Pancreatic cancer is one of the most common malignant diseases in the world. Morbidity rate increases and now reaches around 200 000 new cases yearly. Poor prognosis mainly results from usually late diagnosis and non-specific symptoms. Despite of advances in radiological diagnosis of pancreatic diseases, differentiation between malignant and inflammatory pancreatic tumors still remains difficult. The aim of the studywas the assessment of clinical utility of  CA 19-9 in peripheral and portal blood of patients with pancreatic tumor. Material and methods.66 patients were hospitalized at the Department of General and Transplant Surgery between October 2010 nad July 2012 due to pancreatic tumor. Blood samples were collected from peripheral vein before surgery and intraoperatively from the portal vein to measure CA 19-9 concentration. 57 patients were diagnosed with malignant tumor and 9 with inflammatory lesion. Metastases to the liver were present in 7 of all patients. Radical surgery (Whipple’s procedure in 27 cases) were performed in 34 patients. Results.Significantly higher CA 19-9 concentration in the peripheral blood and in the portal blood as well was found in the pancreatic cancer group than in the inflammatory lesions group (51.2 vs <3 and 52.1 vs 6.3 respectively). Marker concentration in case of malignant lesions was significantly higher in the portal blood than in the peripheral blood (52.1 vs 51.2; p<0.05). CA 19-9 concentration  of patients with malignant pancreatic tumors but without metastases to the liver  was significanlty higher in the portal blood than in the peripheral blood (19.32  vs 18.65; p<0.01). Conclusions.Determination of the CA 19-9 concentration not only in the peripheral blood but in the portal blood as well might be a useful diagnostic tool in order to differentiate between the malignant and inflammatory  pancreatic tumors. We did not see any statistically significant dependency between the CA 19-9 concentrations in the peripheral blood and portal blood and if the surgery was radical or not, but significantly higher concentrations of CA  19-9 in the portal blood than the peripheral blood among the patients suffering from the malignant pancreatic tumor without metastases to the liver might be useful tool when decisions on performing pancreatoduodenectomy are being made since this surgery is forborne from when metastases are present.

 

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[200]

TÍTULO / TITLE:  - The angiotensin II type I receptor blocker olmesartan inhibits the growth of pancreatic cancer by targeting stellate cell activities in mice.