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

Neuroendocrine tumors.

February - March 2013


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TÍTULO / TITLE:  - Case records of the Massachusetts General Hospital. Case 5-2013. A 52-year-old woman with a mass in the thyroid.

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

REVISTA / JOURNAL:  - N Engl J Med. 2013 Feb 14;368(7):664-73. doi: 10.1056/NEJMcpc1210080.

            ●● Enlace al texto completo (gratuito o de pago) 1056/NEJMcpc1210080

AUTORES / AUTHORS:  - Wirth LJ; Ross DS; Randolph GW; Cunnane ME; Sadow PM

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




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.




TÍTULO / TITLE:  - Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer.

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

REVISTA / JOURNAL:  - N Engl J Med. 2013 Feb 14;368(7):623-32. doi: 10.1056/NEJMoa1209288.

            ●● Enlace al texto completo (gratuito o de pago) 1056/NEJMoa1209288

AUTORES / AUTHORS:  - Ho AL; Grewal RK; Leboeuf R; Sherman EJ; Pfister DG; Deandreis D; Pentlow KS; Zanzonico PB; Haque S; Gavane S; Ghossein RA; Ricarte-Filho JC; Dominguez JM; Shen R; Tuttle RM; Larson SM; Fagin JA

INSTITUCIÓN / INSTITUTION:  - Head and Neck Oncology Service, Department of Medicine, Memorial Sloan-Kettering  Cancer Center and Weill Cornell Medical College, New York, NY 10065, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Metastatic thyroid cancers that are refractory to radioiodine (iodine-131) are associated with a poor prognosis. In mouse models of thyroid cancer, selective mitogen-activated protein kinase (MAPK) pathway antagonists increase the expression of the sodium-iodide symporter and uptake of iodine. Their effects in humans are not known. METHODS: We conducted a study to determine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. After stimulation with thyrotropin alfa, dosimetry with iodine-124 positron-emission tomography (PET) was performed before and 4 weeks after treatment with selumetinib (75 mg twice daily). If the second iodine-124 PET study indicated that a dose of iodine-131 of 2000 cGy or more could be delivered to the metastatic lesion or lesions, therapeutic radioiodine was administered while the patient was receiving selumetinib. RESULTS: Of 24 patients screened for the study, 20 could be evaluated. The median age was 61 years (range, 44 to 77), and 11 patients were men. Nine patients had tumors with  BRAF mutations, and 5 patients had tumors with mutations of NRAS. Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients with BRAF mutations and 5 of 5 patients with NRAS mutations). Eight of these 12 patients reached the dosimetry threshold for radioiodine therapy, including all 5 patients with NRAS mutations. Of the 8 patients treated with radioiodine, 5 had confirmed partial responses and 3 had stable disease; all patients had decreases  in serum thyroglobulin levels (mean reduction, 89%). No toxic effects of grade 3  or higher attributable by the investigators to selumetinib were observed. One patient received a diagnosis of myelodysplastic syndrome more than 51 weeks after radioiodine treatment, with progression to acute leukemia. CONCLUSIONS: Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. (Funded by the American Thyroid Association and others; ClinicalTrials.gov number, NCT00970359.).




TÍTULO / TITLE:  - Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d’etude des Tumeurs Endocrines (GTE) cohort study.

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

REVISTA / JOURNAL:  - Hum Mol Genet. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1093/hmg/ddt039

AUTORES / AUTHORS:  - Thevenon J; Bourredjem A; Faivre L; Cardot-Bauters C; Calender A; Murat A; Giraud S; Niccoli P; Odou MF; Borson-Chazot F; Barlier A; Lombard-Bohas C; Clauser E; Tabarin A; Parfait B; Chabre O; Castermans E; Beckers A; Ruszniewski P; Le Bras M; Delemer B; Bouchard P; Guilhem I; Rohmer V; Goichot B; Caron P; Baudin E; Chanson P; Groussin L; Du Boullay H; Weryha G; Lecomte P; Penfornis A; Bihan H; Archambeaud F; Kerlan V; Duron F; Kuhn JM; Verges B; Rodier M; Renard M; Sadoul JL; Binquet C; Goudet P

INSTITUCIÓN / INSTITUTION:  - CHU de Dijon, Centre de Genetique et Centre de Reference Anomalies du Developpement et Syndromes Malformatifs, Universite de Bourgogne, EA4271 GAD Dijon, France.

RESUMEN / SUMMARY:  - Multiple endocrine neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes  mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear, but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities. We report on a cohort of MEN1 patients from the Groupe d’etude des Tumeurs Endocrines. Patients with a molecular diagnosis and a  clinical follow-up, totaling 262 families and 806 patients, were included. Associations between mutation type, location or interacting factors of the MENIN  protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families.  Accounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR = 1.88: 95%-CI = 1.15-3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR = 2.34; 95%-CI = 1.23-4.43). This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and  should thus be considered for surgical indications, genetic counseling and follow-up.




TÍTULO / TITLE:  - A multi-histology trial of fostamatinib in patients with advanced colorectal, non-small cell lung, head and neck, thyroid, and renal cell carcinomas, and pheochromocytomas.

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

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Apr;71(4):981-90. doi: 10.1007/s00280-013-2091-3. Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2091-3

AUTORES / AUTHORS:  - Park SR; Speranza G; Piekarz R; Wright JJ; Kinders RJ; Wang L; Pfister T; Trepel JB; Lee MJ; Alarcon S; Steinberg SM; Collins J; Doroshow JH; Kummar S

INSTITUCIÓN / INSTITUTION:  - Division of Cancer Treatment and Diagnosis, National Cancer Institute, 31 Center  Drive, 3A44, Bethesda, MD, 20892, USA.

RESUMEN / SUMMARY:  - PURPOSE: A multi-cohort phase II study of fostamatinib, an oral multi-kinase inhibitor, was conducted to determine the response rate in patients with advanced colorectal (CRC), thyroid, non-small cell lung, head and neck, and renal cell carcinomas, and pheochromocytomas. METHODS: Patients received 200 mg fostamatinib BID in 4-week cycles with response assessed every 2 cycles. Blood was collected for pharmacokinetic analysis and measurements of circulating tumor cells and circulating endothelial (progenitor) cells (CE(P)Cs). RESULTS: A total of 37 patients (22 CRC), median of 4 prior therapies, were enrolled. Due to toxicities  in four of the first five patients, the study was amended to incorporate a dose escalation phase for each histology. The maximum-tolerated dose was established at 50 mg BID in CRC but was not established for the other cancers. Common grade ¾ toxicities included transaminitis, hyperbilirubinemia, and hypertension. Pharmacokinetic profile was similar to previous reports. Seventy-three percent of CRC patients had liver involvement and 91 % had prior anti-angiogenic therapy. Patients with abnormal liver tests at baseline were more likely to experience grade >/=2 hepatotoxicity than those with normal tests (44 vs. 0 %). No responses were observed; disease stabilization rate was 27 % in CRC. Reduction in CECs following treatment was associated with a better disease stabilization rate (75 vs. 0 %) in CRC. CONCLUSION: Fostamatinib had limited anti-tumor activity in this first clinical trial in patients with advanced refractory solid tumors; reduction in CECs and CEPs was indicative of anti-angiogenic effects. Abnormal liver testing at baseline appeared to influence drug tolerability.




TÍTULO / TITLE:  - Unilateral proptosis.

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

REVISTA / JOURNAL:  - JAMA. 2013 Feb 13;309(6):605-6. doi: 10.1001/jama.2013.233.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jama.2013.233

AUTORES / AUTHORS:  - Munoz J; Kurzrock R

INSTITUCIÓN / INSTITUTION:  - Investigational Cancer Therapeutics (Phase I Clinical Trials Program), MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 455, Houston, TX 77030, USA. jlmunoz@mdanderson.org




TÍTULO / TITLE:  - Peptide receptor radionuclide therapy with Y-DOTATATE/Y-DOTATOC in patients with  progressive metastatic neuroendocrine tumours: assessment of response, survival and toxicity.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Mar 14. doi: 10.1038/bjc.2013.103.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.103

AUTORES / AUTHORS:  - Vinjamuri S; Gilbert TM; Banks M; McKane G; Maltby P; Poston G; Weissman H; Palmer DH; Vora J; Pritchard DM; Cuthbertson DJ

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool, UK, L7 8XP.

RESUMEN / SUMMARY:  - Background:Peptide receptor radionuclide therapy (PRRT) is an established treatment for patients with metastatic neuroendocrine tumours (NETs), although which factors are associated with an improved overall survival (OS) remains unclear. The primary aim of this study is to determine to what extent a radiological response to 90Y-DOTATOC/90Y-DOTATATE PRRT is associated with an improved OS. The association of biochemical and clinical response to OS were assessed as secondary outcome measures.Methods:A retrospective analysis was conducted on 57 patients: radiological response was classified using RECIST criteria, biochemical response was classified using WHO criteria and clinical response was assessed subjectively. Responses were recorded as positive response  (PR), stable disease (SD) or progressive disease (PD), and survival analysed.Results:Radiological response was achieved in 71.5% (24.5% PR, 47% SD) and was associated with a greater OS (51 and 56 months, respectively), compared with PD (18 months). A biochemical or clinical response post PRRT were not associated with a statistically significant improvement in OS. However, when combined with radiological response a survival benefit was observed according to  the number of outcomes (radiological, biochemical, clinical), in which a response was observed. Mild haematological toxicity was common, renal toxicity was rare.Conclusion:In patients with progressive metastatic NETs receiving 90Y-DOTATOC/90Y-DOTATATE PRRT, a radiological response with either a PR or a SD post therapy confers a significant OS benefit.British Journal of Cancer advance online publication, 14 March 2013; doi:10.1038/bjc.2013.103 www.bjcancer.com.




TÍTULO / TITLE:  - Liver Transplantation for Neuroendocrine Tumors in Europe-Results and Trends in Patient Selection: A 213-Case European Liver Transplant Registry Study.

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.0b013e31828ee17c

AUTORES / AUTHORS:  - Le Treut YP; Gregoire E; Klempnauer J; Belghiti J; Jouve E; Lerut J; Castaing D; Soubrane O; Boillot O; Mantion G; Homayounfar K; Bustamante M; Azoulay D; Wolf P; Krawczyk M; Pascher A; Suc B; Chiche L; de Urbina JO; Mejzlik V; Pascual M; Lodge J; Gruttadauria S; Paye F; Pruvot FR; Thorban S; Foss A; Adam R

INSTITUCIÓN / INSTITUTION:  - *Hopital La Conception, Marseille, France daggerMedizinische Hochschule, Hannover, Germany double daggerHopital Beaujon, Clichy, France section signCliniques Universitaires St Luc, Brussels, Belgium ||Hopital Paul Brousse, Villejuif, France paragraph signHopital Cochin, Paris, France **Hopital Edouard Herriot, Lyon, France daggerdaggerHopital Jean Minjoz, Besancon, France double daggerdouble daggerGeorg August Universitat, Gottingen, Germany section sign section signComplexo Hospitalario Universitario, Santiago de Compostela, España || ||Hopital Henri Mondor, Creteil, France paragraph sign paragraph signHopital de Hautepierre, Strasbourg, France ***Medical University, Warsaw, Poland daggerdaggerdaggerCharite Campus Virchow-Klinikum, Berlin, Germany double daggerdouble daggerdouble daggerHopital Rangueil, Toulouse, France section sign section sign section signHopital Cote de Nacre, Caen, France || || ||Hospital de  Cruces, Bilbao, España paragraph sign paragraph sign paragraph signCenter of transplantation, Brno, Czech Republik ****CH Universitaire Vaudois, Lausanne, Switzerland daggerdaggerdaggerdaggerSt James University Hospital, Leeds, United Kingdom double daggerdouble daggerdouble daggerdouble daggerISMETT, Palermo, Italy section sign section sign section sign section signHopital St Antoine, Paris, France || || || ||Hopital Claude Huriez, Lille, France paragraph sign paragraph sign paragraph sign paragraph signTechnische Universitat, Munchen, Germany *****Rikshospitalet, Oslo, Norway.

RESUMEN / SUMMARY:  - OBJECTIVE:: The purpose of thisstudy was to assess outcomes and indications in a  large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period. BACKGROUND:: LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases. METHODS:: This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients  had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25  months (range, 1-149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures. RESULTS:: Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from  diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in  relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors  of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT. CONCLUSIONS:: LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.




TÍTULO / TITLE:  - Somatic uniparental isodisomy explains multifocality of glomuvenous malformations.

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

REVISTA / JOURNAL:  - Am J Hum Genet. 2013 Feb 7;92(2):188-96. doi: 10.1016/j.ajhg.2012.12.017. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajhg.2012.12.017

AUTORES / AUTHORS:  - Amyere M; Aerts V; Brouillard P; McIntyre BA; Duhoux FP; Wassef M; Enjolras O; Mulliken JB; Devuyst O; Antoine-Poirel H; Boon LM; Vikkula M

INSTITUCIÓN / INSTITUTION:  - Laboratory of Human Molecular Genetics, de Duve Institute, Universite catholique  de Louvain, Brussels, Belgium.

RESUMEN / SUMMARY:  - Inherited vascular malformations are commonly autosomal dominantly inherited with high, but incomplete, penetrance; they often present as multiple lesions. We hypothesized that Knudson’s two-hit model could explain this multifocality and partial penetrance. We performed a systematic analysis of inherited glomuvenous malformations (GVMs) by using multiple approaches, including a sensitive allele-specific pairwise SNP-chip method. Overall, we identified 16 somatic mutations, most of which were not intragenic but were cases of acquired uniparental isodisomy (aUPID) involving chromosome 1p. The breakpoint of each aUPID is located in an A- and T-rich, high-DNA-flexibility region (1p13.1-1p12).  This region corresponds to a possible new fragile site. Occurrences of these mutations render the inherited glomulin variant in 1p22.1 homozygous in the affected tissues without loss of genetic material. This finding demonstrates that a double hit is needed to trigger formation of a GVM. It also suggests that somatic UPID, only detectable by sensitive pairwise analysis in heterogeneous tissues, might be a common phenomenon in human cells. Thus, aUPID might play a role in the pathogenesis of various nonmalignant disorders and might explain local impaired function and/or clinical variability. Furthermore, these data suggest that pairwise analysis of blood and tissue, even on heterogeneous tissue, can be used for localizing double-hit mutations in disease-causing genes.




TÍTULO / TITLE:  - In vivo RAF signal transduction as a potential biomarker for sorafenib efficacy in patients with neuroendocrine tumours.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Apr 2;108(6):1298-305. doi: 10.1038/bjc.2013.64. Epub 2013 Feb  14.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.64

AUTORES / AUTHORS:  - Quintela-Fandino M; Krzyzanowska M; Duncan G; Young A; Moore MJ; Chen EX; Stathis A; Colomer R; Petronis J; Grewal M; Webster S; Wang L; Siu LL

INSTITUCIÓN / INSTITUTION:  - 1] Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre,  University Health Network, University of Toronto, 610 University Avenue, Suite 5-718, Toronto, Ontario, Canada M5G2M9 [2] CNIO - Spanish National Cancer Research Center Clinical Program, Melchor Fernandez Almagro 3, Madrid 28029, España.

RESUMEN / SUMMARY:  - Background:Targeted therapies elicit anticancer activity by exerting pharmacodynamic effects on specific molecular targets. Currently, there is limited use of pharmacodynamic assessment to guide drug administration in the routine oncology setting.Methods:We developed a phosphoshift (pShift) flow cytometry-based test that measures RAF signal transduction capacity in peripheral blood cells, and evaluated it in a phase II clinical trial of oral sorafenib plus low-dose cyclophosphamide in patients with advanced neuroendocrine tumours (NETs), in order to predict clinical course and/or guide individual dose-titration.Results:Twenty-two patients were enrolled. Median progression-free survival (PFS) was 3 months (95% CI 2-10.7), and one patient had a partial response. PFS was longer among five patients who demonstrated an increase in pShift after 7 days of sorafenib compared with those who did not (14.9 months vs  2.8 months; P=0.047). However, pShift did not add value to toxicity-based dose-titration.Conclusion:The pharmacodynamic assessment of RAF transduction may  identify selected patients with advanced NETs most likely to benefit from the combination of sorafenib plus cyclophosphamide. Further investigation of this test as a potential biomarker is warranted.




TÍTULO / TITLE:  - Inherited Mutations in Pheochromocytoma and Paraganglioma: Why All Patients Should Be Offered Genetic Testing.

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

REVISTA / JOURNAL:  - Ann Surg Oncol. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2942-5

AUTORES / AUTHORS:  - Fishbein L; Merrill S; Fraker DL; Cohen DL; Nathanson KL

INSTITUCIÓN / INSTITUTION:  - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA,  USA.

RESUMEN / SUMMARY:  - BACKGROUND: Pheochromocytomas (PCC) and paragangliomas (PGL) are neuroendocrine tumors that, although rare, are an important cause of secondary hypertension because of the high morbidity and mortality. PCC/PGL are still thought of as the  “tumor of tens,” with 10 % being hereditary; however, recent population based studies suggest that up to 32 % of patients have a germline mutation in one of the known common susceptibility genes (including NF1, VHL, RET, SDHB, SDHD, and SDHC). Despite this, most patients in the United States are not referred for clinical genetic testing by their physicians. We aimed to examine the mutation prevalence in a clinic-based population in the United States. METHODS: We performed a retrospective chart review of 139 consecutive patients with PCC/PGL from the medical genetics clinic at the hospital of the University of Pennsylvania from January 2004 through February 2012. RESULTS: We found a 41 % overall mutation detection rate. Twenty-six percent of the cohort had a mutation  in the SDHB or SDHD genes. Of patients with at least one PGL tumor outside the adrenal gland, 53 % had an identified mutation. CONCLUSIONS: Forty-one percent of the cohort had a heritable mutation. The most commonly mutated gene was SDHB, which carries the highest risk of malignancy. These data, together with American  Society of Clinical Oncology guidelines suggesting that genetic testing be performed if the risk of a hereditable mutation is at least 10 % or if it will affect medical management, strongly suggest that all patients with PCC/PGL should undergo clinical genetic testing.




TÍTULO / TITLE:  - Tumor staging but not grading is associated with adverse clinical outcome in neuroendocrine tumors of the appendix: a retrospective clinical pathologic analysis of 138 cases.

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

REVISTA / JOURNAL:  - Am J Surg Pathol. 2013 Apr;37(4):606-12. doi: 10.1097/PAS.0b013e318275d1d7.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e318275d1d7

AUTORES / AUTHORS:  - Volante M; Daniele L; Asioli S; Cassoni P; Comino A; Coverlizza S; De Giuli P; Fava C; Manini C; Berruti A; Papotti M

INSTITUCIÓN / INSTITUTION:  - *Department of Clinical & Biological Sciences, University of Turin at San Luigi Hospital, Orbassano daggerDepartment of Biomedical Sciences & Oncology, University of Turin at Molinette Hospital section signDivision of Pathology, Giovanni Bosco Hospital paragraph signDivision of Pathology, Mauriziano Hospital  #Division of Pathology, Santa Croce Hospital, Moncalieri, Turin double daggerDivision of Pathology, Santa Croce Hospital parallelDivision of Pathology,  Alba Hospital, Alba, Cuneo, Italy.

RESUMEN / SUMMARY:  - Appendiceal neuroendocrine neoplasms (NENs) are rare and usually incidentally discovered. Most cases are clinically indolent, although the rare aggressive ones are poorly predictable. The aim of this study was to test the applicability and prognostic significance of the new World Health Organization (WHO) classification and to test the several pathologic features and TNM staging systems (American Joint Committee on Cancer and European Neuroendocrine Tumor Society) in these tumors. A multi-institutional retrospective series of 138 appendiceal NENs was selected on the basis of the availability of both pathologic material and clinical information, including follow-up data. All cases were reviewed to record pathologic features and to apply year 2000 and 2010 WHO classifications, as well  as European Neuroendocrine Tumor Society and American Joint Committee on Cancer TNM stages. Clinical and pathologic characteristics were compared with disease outcome by contingency, univariate, and multivariate survival analyses. Although  up to one third of cases presented several malignancy-associated pathologic features, only 4 patients died of the disease. Adverse outcome was significantly  associated with extramural extension (including mesoappendix), well-differentiated carcinoma diagnosis (2000 WHO classification), pT3-4 stage, older age, and presence of positive resection margins, but not with tumor size, mitotic or proliferative indexes, and, consequently, 2010 WHO grading. In the appendix, at variance with midgut/hindgut NENs, the 2000 WHO classification performs better than the grading-based 2010 WHO scheme and, together with tumor stage, is the most relevant parameter associated with clinical aggressiveness.




TÍTULO / TITLE:  - Bone Metastases and Skeletal-Related Events in Patients with Malignant Pheochromocytoma and Sympathetic Paraganglioma.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-4231

AUTORES / AUTHORS:  - Ayala-Ramirez M; Palmer JL; Hoffman MC; de la Cruz M; Moon BS; Waguespack SG; Habra MA; Jimenez C

INSTITUCIÓN / INSTITUTION:  - Departments of Endocrine Neoplasia and Hormonal Disorders (M.A.-R., M.-C.H., S.G.W., M.A.H., C.J.), Biostatistics (J.L.P.), Palliative Care and Rehabilitation Medicine (M.d.l.C.), and Orthopaedic Oncology (B.S.M.), The University of Texas MD Anderson Cancer Center, Houston, Texas 77030.

RESUMEN / SUMMARY:  - Context:Bone metastases (BM) can cause severe pain, spinal cord compression, pathological fractures, and/or hypercalcemia. These skeletal-related events (SREs) may cause immobilization, loss of independence, poor quality of life, and  reduced survival. There is limited information on the clinical effects of BM and  SREs in patients with malignant pheochromocytoma or sympathetic paraganglioma (PHEO/sPGL).Objectives:We studied the prevalence and clinical characteristics of  BM and SREs in patients with PHEO/sPGL and investigated the risk factors for SRE  development.Design:Using a large institutional database, we conducted a retrospective study of 128 patients with malignant PHEO/sPGL at The University of Texas MD Anderson Cancer Center from 1967 through 2011.Results:Of the patients, 91 (71%) had BM, and 57 of these (63%) developed metachronous BM at a median time of 3.4 years (range, 5 months to 23 years) after the primary tumor diagnosis. Metastatic disease was confined exclusively to the skeleton in 26 of 128 (20%) patients. Sufficient information to assess SRE occurrence was available for 67 patients, and 48 of 67 (72%) patients had at least 1 SRE. The median overall survival for the 128 patients was 12 years for patients with only BM, 7.5 years for patients with nonosseous metastases, and 5 years for patients with both BM and nonosseous metastases (log rank test P value = .005). We were unable to identify factors predictive of SRE development, but the occurrence of a first SRE was associated with the development of subsequent SREs in 48% of subjects. In responsive patients, the use of systemic therapy was associated with fewer SREs (P < .0001).Conclusions:BM and SREs are frequent in patients with malignant PHEO/sPGL. SREs often develop shortly after the diagnosis of BM; severe pain is the most frequent SRE. These patients should be followed long-term by a multidisciplinary team to promptly identify the need for medical or surgical intervention.




TÍTULO / TITLE:  - Neuroendocrine and epithelial phenotypes in small-cell lung cancer: implications  for metastasis and survival in patients.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Mar 21. doi: 10.1038/bjc.2013.112.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.112

AUTORES / AUTHORS:  - Stovold R; Meredith SL; Bryant JL; Babur M; Williams KJ; Dean EJ; Dive C; Blackhall FH; White A

INSTITUCIÓN / INSTITUTION:  - 1] Faculty of Life Sciences, Manchester Academic Health Sciences Centre, University of Manchester, 3.016 AV Hill Building, Manchester M13 9PT, UK [2] Paterson Institute for Cancer Research, University of Manchester, Manchester M20  4BX, UK.

RESUMEN / SUMMARY:  - Background:Small-cell lung cancer (SCLC) has a very aggressive clinical course with early metastasis. This study investigated how the distinctive neuroendocrine characteristics contribute to disease progression and invasion in human SCLC.Methods:The neuroendocrine phenotype (pro-opiomelanocortin (POMC)) was quantified by ELISA in blood samples from 43 SCLC patients. The neuroendocrine (POMC, chromogranin A, neuron-specific enolase, NCAM) and epithelial (cytokeratin and E-cadherin) phenotypes were investigated, using ELISA and immunocytochemistry/immunohistochemistry.Results:In SCLC patients, 16% had elevated circulating POMC, which was associated with significantly worse survival (P=0.02) and liver metastases (P=0.004). In addition, POMC correlated with epithelial-positive circulating tumour cells (P=0.0002). In a panel of SCLC cell  lines, all POMC-secreting cell lines expressed cytokeratin (40% of total). Even after cloning, DMS 79 cells expressed both neuroendocrine and epithelial markers. DMS 79 xenografts secreted POMC into the blood, which mirrored the tumour volume. These xenografts expressed both neuroendocrine and epithelial phenotypes in all tumours, with both phenotypes prevalent in cells invading the surrounding tissue.Conclusion:Both neuroendocrine and epithelial phenotypes coexist in human  SCLC tumours in vitro and in vivo and this persists in invading tumour cells. In  patients, POMC secretion predicts poor survival and liver metastases, suggesting  a crucial role of the neuroendocrine phenotype.British Journal of Cancer advance  online publication, 21 March 2013; doi:10.1038/bjc.2013.112 www.bjcancer.com.




TÍTULO / TITLE:  - Interleukin-1beta promotes skeletal colonization and progression of metastatic prostate cancer cells with neuroendocrine features.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3970

AUTORES / AUTHORS:  - Liu Q; Russell MR; Shahriari K; Jernigan DL; Lioni MI; Garcia FU; Fatatis A

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacology & Physiology, Drexel University College of Medicine.

RESUMEN / SUMMARY:  - Despite the progress made in the early detection and treatment of prostate adenocarcinoma, the metastatic lesions from this tumor are incurable. We used genome-wide expression analysis of human prostate cancer cells with different metastatic behavior in animal models to reveal that bone-tropic phenotypes up-regulate three genes encoding for the cytokine Interleukin-1beta (IL1B, IL-1beta), the chemokine CXCL6 (GCP-2) and the protease inhibitor Elafin (PI3). The Oncomine database revealed that these three genes are significantly upregulated in human prostate cancer versus normal tissue and correlate with Gleason scores >/=7. This correlation was further validated for IL-1beta by immuno-detection in prostate tissue arrays. Our study also shows that the exogenous over-expression of IL-1beta in non-metastatic cancer cells promotes their growth into large skeletal lesions in mice, whereas its knockdown significantly impairs the bone progression of highly metastatic cells. In addition, IL-1beta secreted by metastatic cells induced the over-expression of COX-2 (PTGS2) in human bone mesenchymal cells treated with conditioned media from bone metastatic prostate cancer cells. Finally, we inspected human tissue specimens from skeletal metastases and detected prostate cancer cells positive for both IL-1beta and synaptophysin (SYP) while concurrently lacking prostate specific antigen (PSA, KLK3) expression. Collectively, these findings indicate that IL-1beta supports the skeletal colonization and metastatic progression of prostate cancer cells with an acquired neuroendocrine phenotype.




TÍTULO / TITLE:  - Clinical outcomes for rectal carcinoid tumors according to a new (AJCC 7th edition) TNM staging system: A single institutional analysis of 122 patients.

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

REVISTA / JOURNAL:  - J Surg Oncol. 2013 Mar 15. doi: 10.1002/jso.23327.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jso.23327

AUTORES / AUTHORS:  - Kim MS; Hur H; Min BS; Baik SH; Lee KY; Kim NK

INSTITUCIÓN / INSTITUTION:  - Section of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVES: This study aimed to describe clinical outcomes of rectal carcinoids according to the 7th American Joint Council on Cancer (AJCC) TNM staging system. METHODS: We retrospectively reviewed 122 patients who were treated for rectal carcinoids between 1995 and 2010. RESULTS: Among 122 patients, 81.2% (n = 99) were classified as stage I, 4.9% (n = 6) as stage II, 11.5% (n = 14) as stage III, and 2.5% (n = 3) as stage IV. Lymph node (LN) metastasis rates  for pT1a, 1b, 2, and 3 stages were 1.2% (1/85), 16.7% (3/18), 0% (0/4) and 84.6%  (11/13), respectively. The 5-year overall survival (OS) rate was 88.4%. The 5-year OS rates were estimated to be 100%, 80%, 51.4% and 0% for stage I, II, III, and IV, respectively (P < 0.001). The 5-year disease-free survival (DFS) rate was 82.3%. The 5-year DFS rates were estimated to be 97.7%, 62.5%, 17.1%, and 0% for stages I, II, III, and IV, respectively (P < 0.001). CONCLUSIONS: Using the new TNM stage, we confirmed a prognostic difference in LN metastasis rates, OS, and DFS for rectal carcinoids. In clinical practice, the new TNM stage can be very useful for predicting prognosis. J. Surg. Oncol © 2013 Wiley Periodicals, Inc.




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.




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.




TÍTULO / TITLE:  - First description of Merkel Cell polyomavirus DNA detection in a patient with Stevens-Johnson syndrome.

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

REVISTA / JOURNAL:  - J Med Virol. 2013 May;85(5):918-23. doi: 10.1002/jmv.23550.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jmv.23550

AUTORES / AUTHORS:  - Maximova N; Granzotto M; Kiren V; Zanon D; Comar M

INSTITUCIÓN / INSTITUTION:  - Institute for Maternal and Child Health, IRCCS Burlo Garofolo, University of Trieste, Trieste, Italy.

RESUMEN / SUMMARY:  - Merkel Cell polyomavirus (MCPyV), a ubiquitous DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukaemia while  other associations are still being explored. MCPyV sequences have also been detected in normal tissues of tumor patients and in the blood of healthy donors.  This report documents a new MCPyV association with the Stevens-Johnson syndrome,  a rare immune-modulated mucocutaneous process particularly associated with specific drugs and infective agents. A high MCPyV viral load was detected simultaneously in fluid from skin lesions (2.0 x 10(4) copies/ml) and in matched  blood (7.4 x 10(5) copies/ml) from a young adult patient after bone marrow transplant for a relapsed T-cell acute lymphatic leukaemia. MCPyV clearance concurred with the complete resolution of skin lesions after 5 days of cidofovir  treatment. DNA sequencing classified the amplicons as the European/Italian MKL-1  strain. Given its ubiquitous nature, MCPyV could account for part of Stevens-Johnson syndrome idiopathic cases. J. Med. Virol. 85:918-923, 2013. © 2013 Wiley Periodicals, Inc.




TÍTULO / TITLE:  - FG has no added value in prediction of mortality after partial and radical nephrectomy for chromophobe renal cell carcinoma patients.

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

REVISTA / JOURNAL:  - Mod Pathol. 2013 Feb 1. doi: 10.1038/modpathol.2012.230.

            ●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2012.230

AUTORES / AUTHORS:  - Meskawi M; Sun M; Ismail S; Bianchi M; Hansen J; Tian Z; Hanna N; Trinh QD; Graefen M; Montorsi F; Perrotte P; Karakiewicz PI

INSTITUCIÓN / INSTITUTION:  - Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada.

RESUMEN / SUMMARY:  - Our objective was to test whether FG (FG) is applicable in the context of chromophobe renal cell carcinoma patients treated with partial and radical nephrectomy. Patients (n=1862) with chromophobe renal cell carcinoma treated with partial and radical nephrectomy were identified within the Surveillance, Epidemiology, and End Results (1988-2008). Univariable and multivariable Cox regression analyses were fitted to predict cancer-specific mortality. Discriminant properties were assessed for the conventional four-tiered FG scheme. Additionally, discrimination of the three-tiered FG scheme (1-2 vs 3 vs 4) and the two-tiered FG scheme (1-2 vs 3-4) was also assessed. The statistical significance of the differences in accuracy estimates was compared using the Mantel-Haenszel test. A total of 65 of the 1862 died of the disease. The overall  5-year cancer-specific mortality-free survival rate was 94.8% (95% confidence interval: 93.5-96.2). In univariable analyses, none of the FG strata were significantly associated with cancer-specific mortality. Furthermore, FG was less informative (63%) than tumor size (72%) and tumor stage (69%), using measures of  discrimination in univariable analyses. After accounting for all covariates, prediction of 5-year cancer-specific mortality was 79.0% vs 80.3% accurate, respectively, with vs without the consideration of FG (P=0.01). Similar discrimination estimates were obtained for the modified three-tiered FG scheme (78.5%; P=0.009) and the modified two-tiered FG scheme (79.5%; P=0.02). In conclusion, FG is not an informative predictor of prognosis, defined as cancer-specific mortality, after partial and radical nephrectomy for chromophobe  renal cell carcinoma patients.Modern Pathology advance online publication, 1 February 2013; doi:10.1038/modpathol.2012.230.




TÍTULO / TITLE:  - 68Ga-DOTANOC PET/CT for Baseline Evaluation of Patients with Head and Neck Paraganglioma.

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

REVISTA / JOURNAL:  - J Nucl Med. 2013 Mar 21.

            ●● Enlace al texto completo (gratuito o de pago) 2967/jnumed.112.115485

AUTORES / AUTHORS:  - Sharma P; Thakar A; Suman Kc S; Dhull VS; Singh H; Naswa N; Reddy RM; Karunanithi S; Kumar R; Kumar R; Malhotra A; Bal C

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India; and.

RESUMEN / SUMMARY:  - The purpose of this study was to evaluate the role of 68Ga-labeled DOTANOC PET/CT for baseline evaluation of patients with head and neck paragangliomas (HNPs). METHODS: The data for 26 patients (mean age +/- SD, 34.3 +/- 10.4 y; 50% men) with known or suspected HNPs who underwent 68Ga-DOTANOC PET/CT for staging were retrospectively analyzed. PET/CT was performed after intravenous injection of 132-222 MBq of 68Ga-DOTANOC. The images were evaluated by 2 experienced nuclear medicine physicians in consensus, both qualitatively and quantitatively. The PET/CT findings were grouped as HNPs, paraganglioma at other sites (non-HNPs), and metastatic disease. The size and maximum standardized uptake values (SUVmax)  were measured for all lesions. All of the patients also underwent whole-body 131I-metaiodobenzylgunanidine (131I-MIBG) scintigraphy and conventional imaging (CT/MR imaging) of the head and neck region. Their results were compared with those of 68Ga-DOTANOC PET/CT. RESULTS: 68Ga-DOTANOC PET/CT findings were positive in all 26 patients, and 78 lesions were detected. PET/CT imaging demonstrated 45  HNPS, 10 non-HNPs, and 23 metastatic sites. Fifteen patients (57.6%) had more than one site of disease on PET/CT. Among 45 HNPs, 26 were carotid body tumors (CBTs), 15 glomus jugulare, 3 glomus tympanicum, and 1 laryngeal paraganglioma. A positive correlation was seen between size and SUVmax of HNPs (rho = 0.323; P = 0.030). The SUVmax of the CBTs was higher than that of jugulotympanic paragangliomas (P = 0.026). No correlation was seen between size and SUVmax (rho  = 0.069; P = 0.854) of non-HNPs. The size and SUVmax of non-HNPs were significantly less than those of HNPs (P = 0.029 and 0.047, respectively). 131I-MIBG scintigraphy showed only 30 of the 78 lesions and was inferior to PET/CT (P < 0.0001). Conventional imaging (CT/MR imaging) was positive for 42 of  49 head and neck lesions and was inferior to PET/CT on direct comparison (P = 0.015). A combination of CT/MR imaging and 131I-MIBG scintigraphy detected only 53 of 78 (67.9%) lesions and was also inferior to PET/CT (P < 0.0001). CONCLUSION: 68Ga-DOTANOC PET/CT is useful for the baseline evaluation of patients with HNPs and can demonstrate synchronous paragangliomas at other sites and distant metastases. It is superior to 131I-MIBG scintigraphy and conventional imaging (CT/MR imaging) for this purpose.




TÍTULO / TITLE:  - Suspected pheochromocytoma in a patient with guillain-barre syndrome.

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

REVISTA / JOURNAL:  - Pediatrics. 2013 Mar;131(3):e955-8. doi: 10.1542/peds.2012-1445. Epub 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 1542/peds.2012-1445

AUTORES / AUTHORS:  - Abdel-Salam F; Basu AP; Johnson S; Devlin AM

INSTITUCIÓN / INSTITUTION:  - Great North Children’s Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom NE1 4LP. f.abdel-salam@doctors.org.uk.

RESUMEN / SUMMARY:  - Autonomic instability is well recognized in Guillain-Barre syndrome (GBS), particularly in the acute inflammatory demyelinating polyneuropathy subtype. Hypertension occurs in up to two-thirds of children with GBS but is rarely the main presenting feature. We describe a teenager who presented with tachycardia, dizziness, flushing, and significant hypertension as well as ascending limb weakness and sensory disturbance with areflexia. Because the predominant initial  concern was hypertension, she was referred to pediatric nephrology and appropriate investigations for hypertension were conducted. Her neurologic findings prompted a neurology referral, and a diagnosis of GBS was made. The investigations for hypertension subsequently revealed increased urinary normetadrenaline levels in a range consistent with pheochromocytoma, prompting the question of dual pathology. Both autonomic symptoms and urinary metadrenaline levels subsided with GBS resolution, and further investigations excluded the diagnosis of pheochromocytoma. Our case highlights that significant dysautonomia  can occur in children with GBS, with hypertension being a prominent early feature. Recognition that urinary metadrenalines can increase to levels seen in pheochromocytoma is important in avoiding diagnostic confusion.




TÍTULO / TITLE:  - Mitochondria-Targeted Nitroxide, Mito-CP, Suppresses Medullary Thyroid Carcinoma  Cell Survival in Vitro and in Vivo.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3671

AUTORES / AUTHORS:  - Starenki D; Park JI

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.

RESUMEN / SUMMARY:  - Context:Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the RET proto-oncogene. For MTC therapy, the U.S. Food and Drug Administration recently approved vandetanib and cabozantinib, multikinase inhibitors targeting RET and other tyrosine kinase receptors of vascular endothelial growth factor, epidermal growth factor, or hepatocyte growth factor.  Nevertheless, not all patients with the progressive MTC respond to these drugs, requiring the development of additional therapeutic modalities that have distinct activity.Objective:We aimed to evaluate mitochondria-targeted carboxy-proxyl (Mito-CP), a mitochondria-targeted redox-sensitive agent, for its tumor-suppressive efficacy against MTC.Design:In vitro cultures of 2 human MTC cell lines, TT and MZ-CRC-1, and TT xenografts in mice were treated with Mito-CP  in comparison with vandetanib. The effects on cell survival/death, RET expression, mitochondrial integrity, and oxidative stress were determined.Results:Contrary to vandetanib, Mito-CP induced RET downregulation and strong cytotoxic effects in both cell lines in vitro, including caspase-dependent apoptosis. These effects were accompanied by mitochondrial membrane depolarization, decreased oxygen consumption, and increased oxidative stress in cells. Intriguingly, Mito-CP-induced cell death, but not RET downregulation, was  partially inhibited by the reactive oxygen species scavenger, N-acetyl-cysteine,  indicating that Mito-CP mediates tumor-suppressive effects via redox-dependent as well as redox-independent mechanisms. Orally administered Mito-CP effectively suppressed TT xenografts in mice, with an efficacy comparable to vandetanib and relatively low toxicity to animals.Conclusion:Our results suggest that Mito-CP can effectively suppress MTC cell growth/survival via a mechanism distinct from vandetanib effects. Mitochondrial targeting may be a potential strategy for MTC therapy.




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.




TÍTULO / TITLE:  - Tumoral EPAS1 (HIF2A) mutations explain sporadic pheochromocytoma and paraganglioma in the absence of erythrocytosis.

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

REVISTA / JOURNAL:  - Hum Mol Genet. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1093/hmg/ddt069

AUTORES / AUTHORS:  - Comino-Mendez I; de Cubas AA; Bernal C; Alvarez-Escola C; Sanchez-Malo C; Ramirez-Tortosa CL; Pedrinaci S; Rapizzi E; Ercolino T; Bernini G; Bacca A; Leton R; Pita G; Alonso MR; Leandro-Garcia LJ; Gomez-Grana A; Inglada-Perez L; Mancikova V; Rodriguez-Antona C; Mannelli M; Robledo M; Cascon A

INSTITUCIÓN / INSTITUTION:  - Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, España.

RESUMEN / SUMMARY:  - Pheochromocytomas (PCCs) and paragangliomas (PGLs) are chromaffin-cell tumors that arise from the adrenal medulla and extra-adrenal paraganglia, respectively.  The dysfunction of genes involved in the cellular response to hypoxia, such as VHL, EGL nine homolog 1, and the succinate dehydrogenase (SDH) genes, leads to a  direct abrogation of hypoxia inducible factor (HIF) degradation, resulting in a pseudo-hypoxic state implicated in PCC/PGL development. Recently, somatic post-zygotic mutations in EPAS1 (HIF2A) have been found in patients with multiple PGLs and congenital erythrocytosis. We assessed 41 PCCs/PGLs for mutations in EPAS1 and herein describe the clinical, molecular and genetic characteristics of  the 7 patients found to carry somatic EPAS1 mutations; 4 presented with multiple  PGLs (3 of them also had congenital erythrocytosis), whereas 3 were single sporadic PCC/PGL cases. Gene expression analysis of EPAS1-mutated tumors revealed similar mRNA EPAS1 levels to those found in SDH-gene- and VHL-mutated cases and a significant up-regulation of two hypoxia-induced genes (PCSK6 and GNA14). Interestingly, single nucleotide polymorphism array analysis revealed an exclusive gain of chromosome 2p in three EPAS1-mutated tumors. Furthermore, multiplex-PCR screening for small rearrangements detected a specific EPAS1 gain in another EPAS1-mutated tumor and in three non-EPAS1-mutated cases. The finding  that EPAS1 is involved in the sporadic presentation of the disease not only increases the percentage of PCCs/PGLs with known driver mutations, but also highlights the relevance of studying other hypoxia-related genes in apparently sporadic tumors. Finally, the detection of a specific copy number alteration affecting chromosome 2p in EPAS1-mutated tumors may guide the genetic diagnosis of patients with this disease.




TÍTULO / TITLE:  - Dosimetric analyses of kidneys, liver, spleen, pituitary gland, and neuroendocrine tumors of patients treated with 177Lu-DOTATATE.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar;38(3):188-94. doi: 10.1097/RLU.0b013e3182814ac1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182814ac1

AUTORES / AUTHORS:  - Gupta SK; Singla S; Thakral P; Bal CS

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

RESUMEN / SUMMARY:  - OBJECTIVES: The aim of this work was to calculate the radiation absorbed dose to  kidneys, liver, spleen, pituitary gland, and neuroendocrine tumors (NETs) of patients treated with (177)Lu-DOTATATE. METHODS: We enrolled 61 patients (male/female patients, 40/21) with mean age of 48.1 +/- 15.3 years affected by different types of NETs diagnosed with (68)Ga-DOTANOC PET-CT and biochemical markers. For radiation protection of kidneys, amino acid mixture (lysine and arginine) was coinfused; 3.7 to 7.4 GBq (100-200 mCi) of (177)Lu-DOTATATE was infused to each patient over 30 minutes. Each patient underwent a series of 9 whole-body scans at 30 minutes (prevoid) and 4, 8, 12, 24, 48, 96, 144, and 168 h. The organs included in dosimetric calculation were kidney, liver, spleen, pituitary gland, and NETs. All dosimetric calculations were done using the OLINDA/EXM 1.0 software. RESULTS: Physiological uptake of (177)Lu-DOTATATE was seen in all patients in kidneys, liver, spleen, and pituitary gland. Radiation absorbed doses were calculated: 0.57 +/- 0.09 mGy/MBq for kidneys, 0.27 +/- 0.05  mGy/MBq for liver, 1.17 +/- 0.14 mGy/MBq for spleen, 0.058 +/- 0.011 mGy/MBq for  pituitary gland, and 3.41 +/- 0.68 mGy/MBq for NETs. CONCLUSIONS: The maximum cumulative activity of (177)Lu-DOTATATE that can be safely administered to a patient within permissible renal threshold in our study was found to be 40 GBq (1100 mCi). However, there are considerable interpatient differences in absorbed  doses of all organs requiring individualized dosimetry for optimizing tumor dose.




TÍTULO / TITLE:  - Preoperative detection and predictors of level V lymph node metastasis in patients with papillary thyroid carcinoma (Br J Surg 2013; 100: 497-503).

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

REVISTA / JOURNAL:  - Br J Surg. 2013 Mar;100(4):503-4. doi: 10.1002/bjs.9056.

            ●● Enlace al texto completo (gratuito o de pago) 1002/bjs.9056

AUTORES / AUTHORS:  - Kirkby-Bott J

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, Southampton University Hospital, Tremona Road, Southampton SO16 6YD, UK. james.kirkby1@mac.com




TÍTULO / TITLE:  - Evaluation of Feasibility and Image Quality of 68Ga-DOTATOC Positron Emission Tomography/Magnetic Resonance in Comparison With Positron Emission Tomography/Computed Tomography in Patients With Neuroendocrine Tumors.

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

REVISTA / JOURNAL:  - Invest Radiol. 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLI.0b013e31828234d0

AUTORES / AUTHORS:  - Gaertner FC; Beer AJ; Souvatzoglou M; Eiber M; Furst S; Ziegler SI; Brohl F; Schwaiger M; Scheidhauer K

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Nuclear Medicine and daggerRadiology, Technische Universitaet Muenchen, Klinikum rechts der Isar, Muenchen, Germany.

RESUMEN / SUMMARY:  - OBJECTIVES: The primary aims of this study were to evaluate the feasibility of simultaneous (DOTA-Phe-Tyr)octreotide positron emission tomography (PET)/magnetic resonance (MR) acquisition on a fully integrated PET/MR scanner in patients and to compare the quality of PET images acquired with a PET/MR device with those acquired with a PET/computed tomography (CT) scanner. PATIENTS AND METHODS: Sequential PET/CT and PET/MR imaging was performed in 24 patients with neuroendocrine tumors using a single-injection/dual-imaging protocol. After intravenous injection of Ga-DOTATOC (mean, 120 MBq), PET/CT imaging including low-dose CT was performed at a mean time of 17 minutes post injection, and subsequently, PET/MR imaging including a Dixon sequence for attenuation correction was started at a mean time of 82 minutes post injection. The PET/CT and PET/MR images were analyzed visually using a 4-point scale for quality, coregistration, anatomical correlation, and lesion conspicuity. The standardized  uptake value of background organs and focal lesions was measured and compared between the PET/CT and PET/MR acquisitions. RESULTS: Ga-DOTATOC PET acquired on the PET/MR delivered images with a good diagnostic quality (average visual rating PET/CT, 2.83; PET/MR, 2.08; P < 0.01). The standardized uptake value of focal lesions did not differ between the PET/CT and PET/MR acquisitions (P > 0.3) and correlated in a linear fashion (correlation coefficient rho = 0.90). Lesion conspicuity was slightly, but significantly, higher on the PET/CT acquisitions (PET/CT, 2.71; PET/MR, 2.62; P = 0.01). Positron emission tomography/MR detected  153 of 157 lesions identified by PET/CT; however, there was no difference in sensitivity on a patient basis or organ system basis. Anatomical correlates for focal PET lesions could significantly more often be delineated using MR Dixon images compared with low-dose CT (average visual rating PET/CT, 1.78; PET/MR, 2.30; P < 0.01). Coregistration of functional and morphological data was better on PET/MR compared with PET/CT, which, however, did not reach significance (average visual rating PET/CT, 2.17; PET/MR, 2.46; P = 0.10). CONCLUSIONS: Ga-DOTATOC PET/MR imaging is feasible in patients, with good image quality, and detectability of focal PET lesions was equivalent to PET/CT on a patient basis and organ system basis. Now, the clinical value of Ga-DOTATOC PET/MR with additional diagnostic MR protocols has to be evaluated against PET/CT with multiphase contrast-enhanced CT protocols in future studies.




TÍTULO / TITLE:  - Phase I study of sorafenib in combination with everolimus (RAD001) in patients with advanced neuroendocrine tumors.

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

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Mar 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2118-9

AUTORES / AUTHORS:  - Chan JA; Mayer RJ; Jackson N; Malinowski P; Regan E; Kulke MH

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA, JANG@PARTNERS.ORG.

RESUMEN / SUMMARY:  - PURPOSE: Sorafenib and everolimus are both active against neuroendocrine tumors (NET). Because of potential synergy between VEGF pathway and mTOR inhibitors, we  performed a phase I study to evaluate the safety and feasibility of combining sorafenib and everolimus in patients with advanced NET. METHODS: Patients were treated with everolimus 10 mg daily in combination with sorafenib (dose level 1:  200 mg twice daily; dose level 2: 200 mg per morning, 400 mg per evening) using standard phase I dose escalation design. Dose-limiting toxicity (DLT) was defined within the first cycle (28 days) of therapy. Treatment was continued until tumor  progression, unacceptable toxicity, or withdrawal of consent. Twelve additional patients were treated at the maximum tolerated dose (MTD) level to further characterize safety and a preliminary assessment of activity. RESULTS: One patient in Cohort 1 experienced DLT (grade 3 skin rash); the cohort was expanded  to 6 patients with no further DLTs. All 3 patients in Cohort 2 experienced DLT, consisting of thrombocytopenia, hand-foot skin reaction, and rash/allergic reaction. Sorafenib 200 mg twice daily in combination with everolimus 10 mg daily was established as the MTD. Independently reviewed best objective responses revealed that 62 % of patients had some degree of tumor shrinkage. By RECIST, we  observed partial response in 1 patient, stable disease in 13 patients, and progressive disease in 3 patients. CONCLUSION: Sorafenib 200 mg twice daily with  everolimus 10 mg daily represents the MTD of this combination in patients with advanced NET. While the combination is active, toxicity concerns may preclude more widespread use.




TÍTULO / TITLE:  - Conservative Management of Bilateral Vestibular Schwannomas in Neurofibromatosis  Type 2 Patients: Hearing and Tumor Growth Results.

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

REVISTA / JOURNAL:  - Neurosurgery. 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e31828bae28

AUTORES / AUTHORS:  - Peyre M; Goutagny S; Bah A; Bernardeschi D; Larroque B; Sterkers O; Kalamarides M

INSTITUCIÓN / INSTITUTION:  - 1AP-HP, Hopital Beaujon, Department of Neurosurgery, Clichy, F-92110, France 2Universite Paris 7 - Denis Diderot, Paris, F-75010, France 3AP-HP, Hopital Beaujon, Department of ENT surgery, Clichy, F-92110, France 4AP-HP, Hopital Beaujon, Epidemiology, Biostatistics and Clinical Research Unit, Clichy F-92110,  France.

RESUMEN / SUMMARY:  - BACKGROUND:: As new treatment modalities develop for the management of vestibular schwannomas (VS) in patients with Neurofibromatosis Type 2 (NF2), it remains crucial to ascertain the natural history of the disease. OBJECTIVE:: To determine the relationship between hearing and tumor growth in patients undergoing conservative VS management. METHODS:: Patients harboring bilateral VS with at least one year of radiological follow-up were selected. Conservative management was proposed based on the small tumor size and/or serviceable hearing at presentation. Tumor size was calculated using the two-component box model and reported as Mean Tumor Diameter (MTD). Hearing was evaluated using pure tone average and the AAO-HNS classification. RESULTS:: Forty-six patients harboring 92 VS were included. The mean clinical and radiological follow-up times were 6.0 and 4.2 years, respectively. The mean MTD was 13 mm at presentation and 20 mm at the  end of follow-up. Mean tumor growth rate was 1.8 mm/year. During follow-up, 17 patients (37%) underwent surgery for VS. Surgery-free rate for VS was 88% at 5 years. The number of patients with at least one serviceable ear was 39 (85%) at presentation and 34 (74%) at the end of follow-up, including 22 (66%) with binaural serviceable hearing maintained. There was no statistical correlation between tumor growth rate and preservation of serviceable hearing. Tumor growth rates and age at presentation were inversely correlated. CONCLUSION:: This study  illustrates the high variability among NF2 patients regarding hearing status and  VS growth rate and justifies the choice of initial conservative management in selected cases.




TÍTULO / TITLE:  - Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma Cells Do Not Require Expression of the Viral Small T Antigen.

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

REVISTA / JOURNAL:  - J Invest Dermatol. 2013 Feb 25. doi: 10.1038/jid.2013.82.

            ●● Enlace al texto completo (gratuito o de pago) 1038/jid.2013.82

AUTORES / AUTHORS:  - Angermeyer S; Hesbacher S; Becker JC; Schrama D; Houben R

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, University Hospital Wurzburg, Wurzburg, Germany.

RESUMEN / SUMMARY:  - Increasing evidence suggests that Merkel cell carcinoma (MCC) is caused by the Merkel cell polyomavirus (MCV). The viral sequence encodes for two potential oncoproteins, i.e., the small T antigen (sT) and the large T antigen (LT). Indeed, sT has recently been shown to bear transforming activity. Here, we confirm this observation by demonstrating focus formation upon expression of MCV  sT in NIH3T3 fibroblasts. On the other hand, however, we provide evidence that established MCC cells do not require sT for growth and survival. Silencing of sT  protein expression by two different sT-specific short hairpin RNAs (shRNAs) leads to variable degrees of growth retardation in MCV-positive MCC cell lines. However, these effects are not sT specific, as proliferation of MCV-negative cell lines is similarly affected by these sT shRNAs. Furthermore, ectopic expression of shRNA-insensitive sT does not revert the growth inhibition implicated by sT silencing. Finally, the unambiguous and specific growth inhibition induced by means of an shRNA targeting both T antigens, can be completely rescued by ectopic expression of LT alone, thus demonstrating a dispensable role of sT. Altogether,  our results indicate that MCV LT is more relevant in maintaining the proliferation and survival of established MCC cell lines.Journal of Investigative Dermatology advance online publication, 4 April 2013; doi:10.1038/jid.2013.82.




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.




TÍTULO / TITLE:  - Gadoxetate-enhanced versus diffusion-weighted MRI for fused Ga-68-DOTANOC PET/MRI in patients with neuroendocrine tumours of the upper abdomen.

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

REVISTA / JOURNAL:  - Eur Radiol. 2013 Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00330-013-2785-2

AUTORES / AUTHORS:  - Mayerhoefer ME; Ba-Ssalamah A; Weber M; Mitterhauser M; Eidherr H; Wadsak W; Raderer M; Trattnig S; Herneth A; Karanikas G

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20,  1090, Vienna, Austria, marius.mayerhoefer@meduniwien.ac.at.

RESUMEN / SUMMARY:  - OBJECTIVES: To compare fused gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI (diffusion-weighted imaging) for the assessment of abdominal neuroendocrine tumours (NETs). METHODS: Eighteen patients with suspected or histologically proven NETs of the abdomen were enrolled in this retrospective study. All patients underwent Ga-68-DOTANOC PET/CT for a primary search, staging, or restaging, and received an additional MRI, including dynamic  gadoxetate-enhanced T1-weighted sequences and DWI (b-values 50, 300 and 600). Co-registered gadoxetate-enhanced PET/MRI and PET/DWI were separately analysed for NET lesions by a nuclear medicine physician and a radiologist in consensus. Sensitivity and specificity were calculated on a per-region, per-organ and per-patient basis. RESULTS: Eighty-seven out of 684 anatomical regions, and 23 out of 270 organs, were NET-positive in 14 out of 18 patients. Region-based sensitivities and specificities were 97.7 % and 99.7 % for gadoxetate-enhanced PET/MRI and 98.9 % and 99.7 % for PET/DWI. Organ-based sensitivities and specificities were 91.3 % and 99.6 % for gadoxetate-enhanced PET/MRI and 95.7 % and 99.6 % for PET/DWI. Finally, patient-based sensitivities and specificities were 100 % and 100 % for gadoxetate-enhanced PET/MRI and 100 % and 75 % for PET/DWI. Sensitivities and specificities of the two methods did not differ significantly. CONCLUSIONS: Gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI are equally useful for the assessment of abdominal NETs. KEY POINTS: * Positron emission tomography and magnetic resonance imaging can both assess neuroendocrine tumours. * Fusion of PET/MR imaging provides helpful information. * Gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI assess neuroendocrine tumours equally well. * PET/DWI is inherently simpler than gadoxetate-enhanced PET/MRI. * Only benign hepatic lesions pose a potential diagnostic dilemma for PET/DWI.




TÍTULO / TITLE:  - Extrahepatic disease should not preclude transarterial chemoembolization for metastatic neuroendocrine carcinoma.

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

REVISTA / JOURNAL:  - Ann Surg Oncol. 2013 Apr;20(4):1114-20. doi: 10.1245/s10434-012-2786-4. Epub 2013 Mar 2.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2786-4

AUTORES / AUTHORS:  - Arrese D; McNally ME; Chokshi R; Feria-Arias E; Schmidt C; Klemanski D; Gregory G; Khabiri H; Shah M; Bloomston M

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Riverside Methodist Hospital, Columbus, OH, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Transarterial chemoembolization (TACE) is often utilized for patients with inoperable neuroendocrine carcinoma liver metastases. Often, metastatic disease is not limited to the liver. The impact of extrahepatic disease (EHD) on  outcomes and response after TACE has not been described. METHODS: We reviewed 192 patients who underwent TACE for large hepatic tumor burden, progression of liver  metastases, or poorly controlled carcinoid syndrome due to neuroendocrine carcinoma. Demographics, clinicopathologic characteristics, response to TACE, complications, and survival were compared between patients with (n = 123) and without (n = 69) EHD. RESULTS: Demographics, histopathologic characteristics, and complications were similar between groups. As well, those with and without EHD had similar biochemical (85 vs. 88 %) and radiographic response (76 vs. 79 %) to  TACE (all p = NS); however, symptomatic responses were improved in those with EHD (79 vs. 60 %, p = 0.01). The group without EHD had better overall survival compared to those with EHD disease at the time of TACE (median 62 vs. 28 months,  p = 0.001). DISCUSSION: Although patients with EHD from neuroendocrine carcinoma  experience shorter overall survival after TACE compared to those without EHD, they had similar symptomatic, biochemical, and radiographic response to TACE. Meaningful response to TACE is still possible in the presence of EHD and should be considered, particularly in those with carcinoid syndrome.




TÍTULO / TITLE:  - High Sensitivity of Diffusion-weighted MR Imaging for the Detection of Liver Metastases from Neuroendocrine Tumors: Comparison with T2-weighted and Dynamic Gadolinium-enhanced MR Imaging.

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

REVISTA / JOURNAL:  - Radiology. 2013 Mar 26.

            ●● Enlace al texto completo (gratuito o de pago) 1148/radiol.13121628

AUTORES / AUTHORS:  - d’Assignies G; Fina P; Bruno O; Vullierme MP; Tubach F; Paradis V; Sauvanet A; Ruszniewski P; Vilgrain V

INSTITUCIÓN / INSTITUTION:  - Departments of Radiology, Pathology, Hepatobiliary Surgery, and Gastroenterology, Assistance-Publique Hopitaux de Paris, Hopital Beaujon, 100 bd du General Leclerc, 92110 Clichy, France; Universite Paris Diderot, Sorbonne Paris Cite, INSERM Centre de Recherche Biomedicale Bichat Beaujon, CRB3 U773, Paris, France.

RESUMEN / SUMMARY:  - Purpose:To compare the sensitivity and specificity of diffusion-weighted (DW) magnetic resonance (MR) imaging for identifying liver metastases from neuroendocrine tumor (NET) to those of T2-weighted fast spin-echo (FSE) and three-dimensional dynamic gadolinium-enhanced MR imaging, with surgical and histopathologic findings as the reference standard.Materials and Methods:This retrospective study was approved by institutional review board, and informed consent was waived. Fifty-nine patients with NETs (41 patients with 162 liver metastases, and 18 control subjects with no liver metastases) underwent MR imaging that included DW, T2-weighted FSE, and dynamic gadolinium-enhanced MR sequences. Images were retrospectively reviewed by two abdominal radiologists, independently, for the detection and characterization of liver metastases. MR findings were compared with histopathologic and intraoperative ultrasonography findings for metastasis on a lesion-by-lesion basis to determine the sensitivity  of each MR sequence alone and combined. Specificity was calculated by using the control population. Interreader agreement for each MR sequence and McNemar test were also calculated.Results:There was excellent agreement between observers 1 and 2 for characterizing liver metastases at per-lesion analysis (kappa coefficient: 0.86-1.00). DW MR was more sensitive (observer 1: sensitivity, 71.6% [116 of 162], 95% confidence interval [CI]: 64.2%, 78.0%; observer 2: sensitivity, 71.0% [115 of 162], 95% CI: 63.6%, 77.4%) than T2-weighted FSE (observer 1: sensitivity, 55.6% [90 of 162], 95% CI: 47.9%, 63.0%; observer 2: sensitivity, 55.6% [90 of 162], 95% CI: 47.9%, 63.0%) and dynamic gadolinium-enhanced MR (observer 1: sensitivity, 47.5% [77 of 162], 95% CI: 34.0%, 55.2%; observer 2: sensitivity, 48.1% [78 of 162], 95% CI: 40.6%, 55.8%) (P < .001 for both, McNemar test). The specificity of these sequences ranged from 88.9% to 100% (DW MR vs T2-weighted FSE MR: P > .99, DW MR vs dynamic gadolinium-enhanced MR: P = .61, and T2-weighted FSE MR vs dynamic gadolinium-enhanced MR: P = .61, McNemar test).Conclusion:DW MR imaging was more  sensitive for the detection and characterization of liver metastases from NETs than T2-weighted FSE and dynamic gadolinium-enhanced MR imaging and should be systematically performed.© RSNA, 2013.




TÍTULO / TITLE:  - Joint Guidance on Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors.

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

REVISTA / JOURNAL:  - J Nucl Med. 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 2967/jnumed.113.123190

AUTORES / AUTHORS:  - Delbeke D; Graham MM

INSTITUCIÓN / INSTITUTION:  - Vanderbilt University Medical Center Nashville, Tennessee.




TÍTULO / TITLE:  - Multicentre phase II study of cisplatin-etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study.

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

REVISTA / JOURNAL:  - Ann Oncol. 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt009

AUTORES / AUTHORS:  - Le Treut J; Sault MC; Lena H; Souquet PJ; Vergnenegre A; Le Caer H; Berard H; Boffa S; Monnet I; Damotte D; Chouaid C

INSTITUCIÓN / INSTITUTION:  - Department of Pneumology, Aix en Provence.

RESUMEN / SUMMARY:  - BackgroundThe optimal treatment of large-cell neuroendocrine carcinoma (LCNEC) of the lung remains unclear. Here, our primary objective was to assess the efficacy  of cisplatin-etoposide doublet chemotherapy in advanced LCNEC. Accuracy of the pathological diagnosis and treatment toxicity were assessed as secondary objectives.Patients and methodsProspective, multicentre, single-arm, phase II study with a centralised review of treatment-response and pathological data. Patients had untreated performance status (PS) 0/1 stage IV/IIIB LCNEC and received cisplatin (80 mg/m22 d1) and etoposide (100 mg/m22 d1-3) every 21 days.ResultsEighteen centres included 42 patients (mean age, 59 +/- 9 years; 69%  men; median of four cycles/patient). At least one grade-3/4 toxicity occurred in  59% of patients (neutropaenia, thrombocytopaenia, and anaemia in 32%, 17%, and 12%, respectively). The median progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% confidence interval, CI, 3.1-6.6) and 7.7 months (95% CI, 6.0-9.6), respectively. The centralised pathologist review reclassified 11 of 40 (27.5%) patients: 9 as small-cell lung cancer, 1 as undifferentiated non-small-cell lung cancer, and 1 as atypical carcinoid. Survival data were not significantly changed by excluding the reclassified patients.ConclusionsThe pathological diagnosis of LCNEC is difficult. The outcomes of advanced LCNEC treated with cisplatin-etoposide doublets are poor, similar to those of patients with advanced small-cell lung carcinoma (SCLC).




TÍTULO / TITLE:  - 68Ga DOTA-TATE PET/CT Uptake in Spinal Lesions and MRI Correlation on a Patient With Neuroendocrine Tumor: Potential Pitfalls.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31827a2325

AUTORES / AUTHORS:  - Klinaki I; Al-Nahhas A; Soneji N; Win Z

INSTITUCIÓN / INSTITUTION:  - From the Department of Nuclear Medicine, Imperial College Healthcare NHS Trust, London, UK.

RESUMEN / SUMMARY:  - A 62-year-old female patient with suspected insulinoma underwent Ga DOTA-TATE PET/CT for characterization and staging. This demonstrated a focus of uptake in the pancreas and 3 foci of uptake in the spine. An MRI of the spine performed to  further characterize the lesions revealed the presence of a meningioma and degenerative changes, both of which showed Ga DOTA-TATE uptake. A vertebral metastasis seen on PET was occult on CT and MRI. A vertebral hemangioma had no discrete tracer uptake. Awareness of sources of error in interpreting Ga DOTA-TATE scans is important in order to avoid pitfalls.




TÍTULO / TITLE:  - Malignant Neuroendocrine Tumors: Incidence and Outcomes in Pediatric Patients.

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

REVISTA / JOURNAL:  - Eur J Pediatr Surg. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0033-1333643

AUTORES / AUTHORS:  - Allan B; Davis J; Perez E; Lew J; Sola J

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University of Miami, Miami, Florida, United States.

RESUMEN / SUMMARY:  - Introduction Malignant neuroendocrine tumors (NETs) are rare solid tumors infrequently seen in children. This study examines current incidence trends and outcomes for children with NETs.Materials and Methods The Surveillance Epidemiology and End Results registry was examined for patients between birth and 19 years of age between 1973 and 2005 with NETs.Results Overall, 481 patients were identified with malignant NETs. Tumors were classified as malignant carcinoid (n = 189, 39%), central nervous system tumors (n = 127, 26%), medullary thyroid carcinoma (n = 88, 18%), neuroendocrine carcinoma (n = 50, 10%), pheochromocytoma (n = 17, 3.5%), and paraganglioma (n = 7, 1.5%). Children less than 5 years of age had worse 5-year survival ( < 50 vs. > 76% if older, p = 0.009). Blacks had lower 5-year survival compared with whites (61 vs. 81%, p = 0.001). Tumor locations with favorable prognosis included the appendix, lung, and thyroid ( > 95% 5-year survival), whereas soft tissue and ovary location were associated with poor survival (p < 0.001). In multivariate analysis, distant disease at diagnosis (odds ratio [OR] 14.9; 95% confidence interval [CI], 6.9 to  32.1) and black race (OR 3.3; 95% CI, 1.4 to 7.4) were independent predictors of  death.Conclusion Whites have the highest incidence of pediatric NETs. Colon/rectum, appendix, or thyroid tumor location portends favorable prognosis. Black children and those less than 5 years of age had poorer prognosis.




TÍTULO / TITLE:  - Patient with lingual thyroid and squamous cell carcinoma of the tongue base—case report.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:227-9.

AUTORES / AUTHORS:  - Candrlic B; Pusic M; Kukuljan M; Cvjetkovic N; Matana Z; Miletic D

INSTITUCIÓN / INSTITUTION:  - University of Rijeka, Rijeka University Hospital Center, Department of Radiology, Rijeka, Croatia. barbaracandrlic@yahoo.com

RESUMEN / SUMMARY:  - We demonstrate a rare case of lingual thyroid together with squamous cell carcinoma of the base of tongue. 54-year-old patient presented with left sided lymph node enlargement in regions II, III and IV without any clinical symptoms. Physical examination revealed semicircular bulge at the base of tongue measuring  30 x 20 mm and tumorous lesion was suspected. Neck ultrasound showed pathological enlargement of lymph nodes and FNA of lymph node revealed squamous carcinoma cells in the smear. Further investigation included CT and MRI of the neck depicted ectopic thyroid tissue in base of tongue and enlarged and necrotic lymph nodes in regions II and III. Primary carcinoma could not be depicted. Biopsy of the lingual mass was performed and histology confirmed ectopic thyroid tissue. Physical examination of the oral cavity was repeated and suspicious area on the left side of the tongue base near ectopic thyroidal tissue was identified. Histology after biopsy confirmed squamous cell carcinoma with superficial growth. This case emphasizes the important role that collaboration of radiologist and otorhinolaryngologyst has in correctly diagnosing oropharyngeal pathology. Also,  we underline the importance of careful oropharyngeal region screening in case of  unknown pathologic lymphadenopathy, when the possibility of oropharyngeal cancer  has to be considered.




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.




TÍTULO / TITLE:  - Vitamin D deficiency is associated with greater tumor size and poorer outcome in  Merkel cell carcinoma patients.

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

REVISTA / JOURNAL:  - J Eur Acad Dermatol Venereol. 2013 Feb 1. doi: 10.1111/jdv.12101.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jdv.12101

AUTORES / AUTHORS:  - Samimi M; Touze A; Laude H; Le Bidre E; Arnold F; Carpentier A; Gardair C; Carlotti A; Maubec E; Dupin N; Aubin F; Avril MF; Rozenberg F; Avenel-Audran M; Guyetant S; Lorette G; Machet L; Coursaget P

INSTITUCIÓN / INSTITUTION:  - INRA ISP, UMR 1282, Tours, France; Universite Francois Rabelais, Tours, France; CHRU de Tours, Service de Dermatologie, Tours, France.

RESUMEN / SUMMARY:  - BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study  was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens  investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.




TÍTULO / TITLE:  - Practical guide to supportive care of patients with functional neuroendocrine tumors.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):45-55. doi: 10.1053/j.seminoncol.2012.11.002.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.002


INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Markey Cancer Center, University of Kentucky, Lexington,  KY 40536, USA. Lowell.anthony@uky.edu

RESUMEN / SUMMARY:  - Supportive care of patients with functional neuroendocrine tumors (NETs) has evolved to include the use of multiple targeted agents to control paraneoplastic  states and newer surgical and interventional radiologic techniques to reduce tumor bulk. Challenges encountered by the clinician are the recognition of specific symptom complexes, selecting the relevant laboratory tests and radiologic/scintigraphic scans, and the timing of intervention(s). Individual variables such as the severity of symptoms in the context of primary and metastatic disease sites, tumor bulk, comorbidities, and previous treatment are factors determining the prioritization of specific treatment regimens for patients with functional NETs. Symptoms such as flushing, secretory diarrhea, hypercalcemia, hyper /hypoglycemia, hypercortisolism, and peptic ulcers should improve with decreasing the elevated amino acid and/or peptide levels produced by NETs. These paraneoplastic symptoms may be accompanied by complaints related to tumor burden such as fatigue, pain, early satiety, anorexia, weight loss, night sweats, and/or symptoms secondary to adverse drug effects such as mucositis, dysgeusia, diarrhea, rash, hypertension, and myelosuppression. Developing a comprehensive continuum of care plan early in disease management assists in controlling the presenting signs and symptoms, and in minimizing disease- and/or  treatment-related side effects. This guide serves as a framework to manage the signs and symptoms of metastatic functional neuroendocrine tumors.




TÍTULO / TITLE:  - Primary High-grade Neuroendocrine Carcinoma of the Esophagus: A Clinicopathologic and Immunohistochemical Study of 42 Resection Cases.

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

REVISTA / JOURNAL:  - Am J Surg Pathol. 2013 Apr;37(4):467-83. doi: 10.1097/PAS.0b013e31826d2639.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e31826d2639

AUTORES / AUTHORS:  - Huang Q; Wu H; Nie L; Shi J; Lebenthal A; Chen J; Sun Q; Yang J; Huang L; Ye Q

INSTITUCIÓN / INSTITUTION:  - *Department of Pathology, the Nanjing Drum Tower Hospital, Nanjing, China Departments of daggerPathology and Laboratory Medicine section signThoracic Surgery, Veterans Affairs Boston Healthcare System, West Roxbury double daggerHarvard Medical School, Boston, MA parallelTulane University School of Medicine, New Orleans, LA.

RESUMEN / SUMMARY:  - Primary high-grade neuroendocrine carcinoma of the esophagus (HNCE) is rare and poorly understood. In this study, we aimed at delineating the clinicopathologic and immunohistochemical characteristics of HNCE diagnosed on the basis of the World Health Organization criteria for pulmonary neuroendocrine carcinomas. We identified 42 (3.8%) consecutive resection cases of HNCE among 1105 esophageal cancers over a 7-year period. Patients’ mean age was 62 years (range, 47 to 79 y) with a male to female ratio of 3.7. Dysphagia was present in 79% of patients and  tobacco abuse in 50%. Most tumors were centered in the middle (52%) or lower (36%) esophagus; 48% were ulcerated and 31% exophytic. All tumors were sharply demarcated with a pushing border in either solid sheet (83%) or nodular (17%) growth patterns. Pure HNCE was found in 57%, and the remainder also exhibited small components of squamous cell carcinoma (SqCC) or glandular, signet ring cell differentiations. SqCC in situ was present in 50%. Most tumors (88%) were the small cell type with pure oat-like cells in 52%, and the larger spindled, anaplastic, and giant cells were common. Tumor crush artifact (98%) and the Azzopardi effect (88%) were widespread. Extensive lymphovascular (50%) and perineural (33%) invasion and metastasis to regional (48%) and abdominal celiac lymph nodes (29%) were observed. Neoplastic cells were immunoreactive to synaptophysin (100%), CD56 (93%), chromogranin A (67%), p63 (55%), TTF-1 (71%), CK8/18 (90%), CD117 (86%), HER2 (16%), and p16 (84%) antibodies. The 5-year survival rate was 25%, similar to that of SqCC. Lymphovascular and perineural invasion was associated with a worse prognosis.




TÍTULO / TITLE:  - Molecular Pathogenesis of Neuroendocrine Tumors: Implications for Current and Future Therapeutic Approaches.

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

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3458

AUTORES / AUTHORS:  - Oberg KE; Casanovas O; Castano JP; Chung DC; Delle Fave G; Denefle P; Harris P; Khan MS; Kulke MH; Scarpa A; Tang LH; Wiedenmann B

INSTITUCIÓN / INSTITUTION:  - Endocrine Oncology Unit, University of Uppsala.

RESUMEN / SUMMARY:  - The treatment landscape and biological understanding of neuroendocrine tumors (NETs) has shifted dramatically in recent years. Recent studies have shown that somatostatin analogs have the potential to not only control symptoms of hormone hypersecretion, but also have the ability to slow tumor growth in patients with advanced carcinoid. The results of clinical trials have further shown that the vascular endothelial growth factor (VEGF) pathway inhibitor sunitinib and the mammalian target of rapamycin (mTOR) inhibitor everolimus have efficacy in patients with advanced pancreatic NETs. The efficacy of these targeted therapies  in NET suggests that the molecular characterization of NETs may provide an avenue to both predict which patients may most benefit from treatment and to overcome potential drug resistance. Recent genomic studies of NETs have further suggested  that pathways regulating chromatin remodeling and epigenetic modification may play a key role in regulating NET growth. These observations offer the potential  for new therapeutic and diagnostic advances for patients with NET.




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.




TÍTULO / TITLE:  - First Report of Bilateral Pheochromocytoma in the Clinical Spectrum of HIF2A-Related Polycythemia-Paraganglioma Syndrome.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2013-1217

AUTORES / AUTHORS:  - Taieb D; Yang C; Delenne B; Zhuang Z; Barlier A; Sebag F; Pacak K

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine (D.T.), La Timone University Hospital, Centre Europeen de Recherche en Imagerie Medicale, Aix-Marseille University, 13005 Marseille, France; Surgical Neurology Branch (C.Y., Z.Z.), National Institute of  Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892; Department of Endocrinology (B.D.), Aix-en-Provence General Hospital, 13616 Aix-en-Provence France; Laboratory of Biochemistry and Molecular  Biology (A.B.), Conception Hospital, Aix-Marseille University, 13005 Marseille, France; Department of Endocrine Surgery (F.S.), La Timone University Hospital, Aix-Marseille University, 13005 Marseille, France; and Program in Reproductive and Adult Endocrinology (K.P.), Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, Maryland 20892.

RESUMEN / SUMMARY:  - Context:Molecular genetic research has so far resulted in the identification of 10 well-characterized susceptibility genes for hereditary pheochromocytoma (PHEO) or paraganglioma (PGL). Recently, a new syndrome characterized by multiple PGLs and somatostatinomas associated with congenital polycythemia due to somatic mutations in HIF2A has been reported.Objective:The aim of the study was to define the genetic defect in a new case of bilateral PHEO and multiple PGLs associated with congenital polycythemia.Patient:A female patient presented with neonatal polycythemia (treated by phlebotomies, 1 session approximately every 4 mo), mildly enlarged cerebral ventricles, and bilateral PHEO and multiple PGLs. There  was no family history of any neuroendocrine tumor or polycythemia. Surgical removal of the tumors only temporarily normalized plasma erythropoietin (Epo) levels and discontinued phlebotomies. No germline mutations were initially detected in the SDHB, SDHC, SDHD, VHL, and PHD2 genes, known to be associated with polycythemia. The PHEOs presented with a typical noradrenergic biochemical phenotype.Results:A heterozygous missense mutation (c.1589C>T) was identified in  exon 12 of HIF2A, resulting in an alanine 530 substitution in the HIF-2alpha protein with valine (A530V). This somatic mutation was detected in the tissue from 1 PHEO and 1 PGL, with no HIF2A germline mutation found. This mutation led to stabilization of HIF-2alpha and hence a gain-of-function phenotype, as in previously published studies.Conclusion:This case represents the first association of a somatic HIF2A gain-of-function mutation with PHEO and congenital polycythemia, and it alerts physicians to perform proper genetic screening in patients presenting with multiple norepinephrine-producing PHEOs and polycythemia. This report also extends the previous findings of a new syndrome of only multiple PGLs, somatostatinomas, and polycythemia to multiple PHEOs.




TÍTULO / TITLE:  - Prognostic value and management of spinal tumors in neurofibromatosis type 2 patients.

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

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-012-1590-z

AUTORES / AUTHORS:  - Aboukais R; Baroncini M; Zairi F; Bonne NX; Schapira S; Vincent C; Lejeune JP

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Lille University Hospital, rue E. Laine, 59037, Lille cedex, France, rabihdoc@hotmail.com.

RESUMEN / SUMMARY:  - PURPOSE: Neurofibromatosis type 2 (NF2) is a well-studied disease. Although spinal tumors are frequent, many issues concerning their prognosis and management still have to be clarified. The authors studied the clinical impact and radiological progression of spinal tumors in patients with NF2 to determine their prognostic value. METHODS: A total of 80 NF2 patients were followed in the Lille  University Hospital between 1987 and 2011. Clinical, radiological and genetic data were retrospectively recorded and analyzed. Patients underwent annual cranial and spinal MRI. Both the location and size of each tumor were reported. The diagnosis of NF2 was confirmed either because the patient met the Manchester  criteria or by the presence of genetic mutation. RESULTS: The mean follow-up period was 8.8 years (range 1 to 24 years; SD: +/-0.8), and the mean age at diagnosis was 27.2 years (range 6 to 73 years; SD: +/-1.7). Among all patients, 48 harbored spinal tumors. Twenty of them were symptomatic, and 21 were operated  on. Patients with spinal tumors had a lower age at diagnosis (p = 0.02), a higher number of intracranial meningiomas (p = 0.028) and schwannomas (p = 0.03), and more nonsense and frameshift mutations (p = 0.04). CONCLUSION: Spinal tumors are  common in NF2, and all patients should be regularly monitored by spinal MRI. The  presence of spinal tumors seems to be a factor indicating poor prognosis. Clinical and radiological monitoring of spinal tumors could lead to early treatment both when clinical symptoms are present and in case of proven radiological evolution, maintaining a favorable functional prognosis as long as possible.




TÍTULO / TITLE:  - Metastatic Mediastinal Carcinoid Presenting as Superior Mediastinal Syndrome and  Treated With Peptide Receptor Radionuclide Therapy.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182815cff

AUTORES / AUTHORS:  - Malhotra G; Asopa RV

INSTITUCIÓN / INSTITUTION:  - From the Radiation Medicine Centre, Parel, Mumbai, India.

RESUMEN / SUMMARY:  - A 43-year-old man with known superior mediastinal syndrome due to Tc HYNIC DOTA SPECT/CT and F-FDG PET tracer avid inoperable metastatic carcinoid received peptide receptor based radionuclide therapy (PRRT) with Lu-DOTATATE. Repeat evaluation at 3 months post-therapy demonstrated stable disease with alleviation  of patient’s symptoms and remarkable improvement in the quality of life. PRRT with Lu-DOTATATE may be an option for inoperable mediastinal carcinoids with superior mediastinal syndrome.




TÍTULO / TITLE:  - The prevalence of Merkel cell polyomavirus in Japanese patients with Merkel cell  carcinoma.

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

REVISTA / JOURNAL:  - J Dermatol Sci. 2013 Mar 6. pii: S0923-1811(13)00066-2. doi: 10.1016/j.jdermsci.2013.02.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jdermsci.2013.02.010

AUTORES / AUTHORS:  - Hattori T; Takeuchi Y; Takenouchi T; Hirofuji A; Tsuchida T; Kabumoto T; Fujiwara H; Ito M; Shimizu A; Okada E; Motegi SI; Tamura A; Ishikawa O

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan. Electronic address: tohatt@gunma-u.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: A novel polyomavirus, the Merkel cell polyomavirus (MCPyV) has been implicated in the pathogenesis of Merkel cell carcinoma (MCC); however, the prevalence of MCPyV in Japan has not been extensively investigated. OBJECTIVE: To clarify the prevalence of MCPyV in Japanese patients with MCC. METHODS: MCPyV DNA was examined by polymerase chain reaction (PCR) in formalin-fixed paraffin-embedded (FFPE) or frozen tissue samples from 26 patients with MCC diagnosed in four medical centers in Japan. Immunohistochemistry was simultaneously performed using a monoclonal antibody against the viral large T (LT) antigen. FFPE samples from basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were also analyzed as controls. RESULTS: Twenty-three out of 26 cases (88.5%) were positive for MCPyV DNA by PCR. The amplified products harbored 4 patterns of mutations. Phylogenetic analysis demonstrated that one of our strains was closely related to the other Japanese strains previously reported. The LT antigen was expressed in various degrees in 20 of 26 cases (76.9%) by immunohistochemistry. Histological type had little relation to CM2B4 positivity,  whereas 3 of 5 trabecular-type tumors showed no staining. The immunoreactivity for CM2B4 did not correlate with the relative viral DNA load. In BCC and SCC, the LT antigen was immunohistochemically positive, but MCPyV DNA was not detected by  PCR. The cells around some MCC and non-MCC tumors were stained with CM2B4 with a  distribution similar to CD20- and CD45RO- (especially CD8-) positive lymphocytes. CONCLUSION: MCPyV was highly positive in Japanese patients with MCC. It is of note that the positive rate differs depending upon the detection method.




TÍTULO / TITLE:  - Tumor-Specific T Cells in Human Merkel Cell Carcinomas: A Possible Role for Tregs and T-Cell Exhaustion in Reducing T-Cell Responses.

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

REVISTA / JOURNAL:  - J Invest Dermatol. 2013 Feb 18. doi: 10.1038/jid.2013.75.

            ●● Enlace al texto completo (gratuito o de pago) 1038/jid.2013.75

AUTORES / AUTHORS:  - Dowlatshahi M; Huang V; Gehad AE; Jiang Y; Calarese A; Teague JE; Dorosario AA; Cheng J; Nghiem P; Schanbacher CF; Thakuria M; Schmults CD; Wang LC; Clark RA

INSTITUCIÓN / INSTITUTION:  - Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

RESUMEN / SUMMARY:  - Merkel cell carcinomas (MCCs) are rare but highly malignant skin cancers associated with a recently described polyomavirus. MCC tumors were infiltrated by T cells, including effector, central memory, and regulatory T cells. Infiltrating T cells showed markedly reduced activation as evidenced by reduced expression of  CD69 and CD25. Treatment of MCC tumors in vitro with IL-2 and IL-15 led to T-cell activation, proliferation, enhanced cytokine production, and loss of viable tumor cells from cultures. Expanded tumor-infiltrating lymphocytes showed TCR repertoire skewing and upregulation of CD137. MCC tumors implanted into immunodeficient mice failed to grow unless human T cells in the tumor grafts were depleted with denileukin diftitox, suggesting that tumor-specific T cells capable of controlling tumor growth were present in MCC. Both CD4+ and CD8+ FOXP3+ regulatory T cells were frequent in MCC. Fifty percent of nonactivated T cells in MCC-expressed PD-1, a marker of T-cell exhaustion, and PD-L1 and PD-L2 were expressed by a subset of tumor dendritic cells and macrophages. In summary, we observed tumor-specific T cells with suppressed activity in MCC tumors. Agents that stimulate T-cell activity, block regulatory T cell function, or inhibit PD-1 signaling may be effective in the treatment of this highly malignant skin cancer.Journal of Investigative Dermatology advance online publication, 4 April 2013; doi:10.1038/jid.2013.75.




TÍTULO / TITLE:  - Secondary malignancy in patients with sporadic neuroendocrine neoplasia.

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

REVISTA / JOURNAL:  - Endocrine. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12020-013-9911-4

AUTORES / AUTHORS:  - Krausch M; Raffel A; Anlauf M; Schott M; Lehwald N; Krieg A; Kropil F; Cupisti K; Knoefel WT

INSTITUCIÓN / INSTITUTION:  - Department of General, Visceral and Pediatric Surgery, Heinrich-Heine-University  Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany, krausch@med.uni-duesseldorf.de.

RESUMEN / SUMMARY:  - The incidence of neuroendocrine neoplasias (NENs), especially of the gastro-entero-pancreatic (GEP), system relatively increased over the past decades, as a result of advanced diagnostic tools, a better clinical awareness, and distinguished pathological diagnostic recognition. Previous reports hypothesized an increased risk for secondary malignancies in patients with NEN especially in GEP-NENs. The present study was designed to investigate the coincidence of NENs and secondary malignancies in a large patient collective. A retrospective analysis was performed on 161 patients (85 female and 76 male) with NEN of various origins. Clinical data of these patients, different classification systems (TNM/WHO), proliferations-based grading, and clinical follow-up were collected and analyzed. Out of 143 patients with a sporadic NEN, 15 (10.49 %) patients were identified with secondary malignant tumors. Median age at the time  of the primary operation for NEN was 65 years, whereas the median age of initial  diagnosis of associated tumors was 59 years. Mean follow-up time was 61 months. The risk of developing a secondary malignancy was most elevated for patients with an NEN of the lung, the stomach, and the ileum (60, 50 and 20 %, respectively). The spectrum of secondary malignancies included various types of cancer. Kaplan-Meier survival analysis shows a difference suggesting that patients with a secondary malignancy demonstrate a worse survival compared to patients without a  secondary tumor; no significance was detected (p = 0.349). Our data suggest that  secondary malignancies in patients with NEN’s especially in GEP-NENs are found more frequently than in general population. Therefore, patients with NEN need a continuous and detailed follow-up. The reason for the increased incidence of secondary malignancies in patients with NENs remains to be elucidated.




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.




TÍTULO / TITLE:  - Disomy as the Genetic Underlying Mechanisms of Loss of Heterozigosity in SDHD-Paragangliomas.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-4083

AUTORES / AUTHORS:  - Beristain E; Vicente MA; Guerra I; Gutierrez-Corres FB; Garin I; de Nanclares GP

INSTITUCIÓN / INSTITUTION:  - Molecular (Epi)Genetics Laboratory (E.B., I.Ga., G.P.d.N.), Endocrinology and Nutrition Service (M.-A.V.), and Pathology Service (I.Gu., F.-B.G.-C.), Hospital  Universitario Araba-Txagorritxu, BioAraba, 01009 Vitoria-Gasteiz, España.

RESUMEN / SUMMARY:  - Context:Succinate dehydrogenase complex, subunit D (SDHD) mutations cause pheochromocytoma/paraganglioma syndrome. SDHD, located at chromosome 11q23, shows a parent-of-origin effect because the disease is observed almost exclusively when the mutation is transmitted from the father, although some cases of maternal transmission have been reported. Several hypotheses have been proposed for this peculiar inheritance pattern, but the underlying mechanisms have not yet been clearly elucidated.Objective:The objective of the study was to explain the parent-of-origin effect in a family, mainly affected by paternally transmitted paragangliomas, and with a maternally transmitted renal tumor.Patients:Peripheral blood DNA from 15 carriers and 7 tumor DNA samples from SDHD-p.Trp5* carriers were studied.Methods:We conducted mutation genotyping and microsatellite marker analysis in germline and tumor DNA and methylation status analysis in tumor DNA by methylation-specific multiplex ligation-dependent probe amplification.Results:Mutation genotyping and microsatellite marker analysis demonstrated loss of heterozygosity of the wild-type allele (maternal) in all studied tumors, except the renal tumor, which lost the mutated allele (maternal), and the prostate tumor, which had no loss of heterozygosity. The methylation-specific multiplex ligation-dependent probe amplification demonstrated that the methylation profile corresponded exclusively to the paternal chromosome without genomic loss, suggesting paternal uniparental disomy  as the mechanism underlying the parent-of-origin effect in this SDHD family.Conclusions:The paternal uniparental disomy involves the loss of maternally imprinted cell cycle regulators and the overexpression of paternally imprinted growth activators, leading to tumorigenesis in this syndrome.




TÍTULO / TITLE:  - FDG-PET Imaging in Patients With Pulmonary Carcinoid Tumor.

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.0b013e318279f0f5

AUTORES / AUTHORS:  - Moore W; Freiberg E; Bishawi M; Halreiner MS; Matthews R; Baram D; Bilfinger TV

INSTITUCIÓN / INSTITUTION:  - From the Department of Radiology, Stony Brook University Medical Center, Stony Brook, NY.

RESUMEN / SUMMARY:  - PURPOSE: This study aimed to assess the imaging findings in patients with pathologically proven carcinoid tumors and determine if SUV can help to differentiate typical from atypical (more aggressive) pulmonary carcinoid tumors. PATIENTS AND METHODS: A retrospective review of patients with a biopsy-proven diagnosis of a pulmonary carcinoid tumor at our institution from 2002 to 2010 that had a preoperative PET scan was performed after institutional review board approval was obtained. PET results, including SUV uptake and location, were recorded as well as all data from pathology reports. Carcinoids were considered to be more aggressive if they showed pathological diagnosis consistent with atypical carcinoid, lymph node invasion, poor histological grade (poorly differentiated), or evidence of systemic metastases. Atypical carcinoid pathology consisted of focal necrosis or a higher mitotic index (2-10 per square millimeter) with features of nests, trabeculae, pleomorphic cells, or dense hyperchromasia. SUV uptake was then evaluated and compared between the typical and atypical carcinoid groups using nonparametric statistical methods. RESULTS: We identified 29 patients from 2002 to 2010 at our institution with a pathological diagnosis of pulmonary carcinoid. Twenty-three were histopathologically typical, and the other 6 showed atypia. Mean (SD) nodule size was 2.4 (1.3) cm in the typical group versus 5.0 (3.2) cm in the atypical group (P = 0.065). Mean (SD) SUV uptake in the typical carcinoid group was 2.7 (1.6) and in the atypical group the SUV was 8.1 (4.1) (P < 0.01). A cutoff SUV of 6 or  greater is predictive of malignancy (odds ratio, 23.6; P < 0.01), as well as a nodule size of 3.5 cm or greater (odds ratio, 5.1; P = 0.024). CONCLUSIONS: Preoperative PET imaging result is frequently positive in carcinoid tumors, and the biological behavior correlates well with SUV; however, size is not as strong  of a predictor of malignancy. Size of 3.5 cm or greater and SUV of 6 or greater have a predictive value of greater than 95% for malignant histology.




TÍTULO / TITLE:  - The value of serum thyreoglobulin levels and whole body (I-131) scintigraphy in the follow-up of the thyroid cancer patients after thyroidectomy.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:67-71.

AUTORES / AUTHORS:  - Kucukalic-Selimovic E; Alagic J; Valjevac A; Hadzovic-Dzuvo A; Begic A; Beslic N

INSTITUCIÓN / INSTITUTION:  - Clinical Center University of Sarajevo, Clinic for Nuclear Medicine, Sarajevo, Bosnia and Herzegovina. elma.kucukalic@yahoo.com

RESUMEN / SUMMARY:  - Serum thyreoglobulin (Tg) and whole body scintigraphy (I-131 WBS) have been used  to detect recurrent and metastatic thyroid cancers postoperatively. However, discordant results of Tg measurement and 131I WBS have been reported. Negative 131I WBS and a positive Tg test are usually found, but less common occurrence of  positive 131I WBS and a negative Tg test has also been demonstrated in a small but significant number of cases. Therefore, the aim of the study was to retrospectively analyse patients with positive 131I WBS after total thyreoidectomy and again 1 year after the radioactive iodine. There were 52 patients included in the study. Four weeks after surgery, during which thyroid hormone treatment was not introduced, each patient received an ablative dose of 131I. The evaluation of the WBS was qualitative and considered positive if thyroid remnant, lymphatic node or metastasis were detected. WBS and serum Tg was measured 12 months after 131I ablation with thyroid hormone suppression. We considered positive any Tg level above the sensitivity values and negative if lower than this level. Tg levels were related to the existence of a positive scan or a negative one. In our 52 WBS positive patients concordant positive Tg levels  were observed in 42 patients while in 10 patients we found a negative Tg levels after the surgery. After 1-year follow-up, out of initially 42 concordant patients 8 patients showed remaining concordant positive Tg and WBS values. Discordant results were observed in 13 patients (4 patients were Tg- and WBS+ while 9 patients were Tg+ and WBS-). In the majority of patients (50%) remained with concordant results but changed from Tg+ and WBS+ to Tg- and WBS-. Diagnostic WBS is an additional valuable tool, besides Tg levels, in the follow up of patients after total thyreoidectomy.




TÍTULO / TITLE:  - Cardiac paraganglioma.

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

REVISTA / JOURNAL:  - J Am Coll Cardiol. 2013 Mar 7. pii: S0735-1097(13)00931-5. doi: 10.1016/j.jacc.2012.10.061.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jacc.2012.10.061


INSTITUCIÓN / INSTITUTION:  - Department of Ultrasound, Second Affiliated Hospital, the Third Military Medical  University, Chongqing, 400037 China. Electronic address: digitalheart@163.com.




TÍTULO / TITLE:  - Merkel Cell Polyomavirus Detection in a Patient with Familial Epidermodysplasia Verruciformis.

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

REVISTA / JOURNAL:  - Pediatr Dermatol. 2013 Mar 28. doi: 10.1111/pde.12130.

            ●● Enlace al texto completo (gratuito o de pago) 1111/pde.12130

AUTORES / AUTHORS:  - Kwon EK; Halvorson CR; Rady P; Tyring S; Nguyen HP; Kao GF; Gaspari AA

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, School of Medicine, University of Maryland, Baltimore, Maryland.

RESUMEN / SUMMARY:  - We report a case of Merkel cell polyomavirus detection in the skin of a patient with epidermodysplasia verruciformis (EDV) and a family history remarkable for an unusual inheritance pattern for EDV.




TÍTULO / TITLE:  - Immunohistochemical evidence for an impairment of autophagy in tumorigenesis of gastric carcinoids and adenocarcinomas in rodent models and patients.

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

REVISTA / JOURNAL:  - Histol Histopathol. 2013 Apr;28(4):531-42. Epub 2013 Feb 7.

AUTORES / AUTHORS:  - Vigen RA; Kodama Y; Viset T; Fossmark R; Waldum H; Kidd M; Wang TC; Modlin IM; Chen D; Zhao CM

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

RESUMEN / SUMMARY:  - Background/Aim: Autophagy has dual roles in tumorigenesis: tumor-promoting or tumor-suppressing. The aim of the present study was to examine autophagy-related  markers by immunohistochemistry in gastric carcinoids and adenocarcinomas in rodent models and patients. Methods: Gastric carcinoids in Mastomys were induced  by loxtidine treatment. Spontaneously developed gastric adenocarcinomas in Japanese cotton rats and INS-GAS transgenic mice were included. Patient tissue samples of gastric carcinoids or adenocarcinomas were collected. Immunohistochemistry was performed against autophagy-related gene protein-6 (ATG-6, also called beclin-1), ATG-5 and ATG-16. Results: In tumor-free Mastomys, ATG-5, ATG-16 and beclin-1 were immunepositive in the gastric mucosa. In tumor-bearing Mastomys, ATG-5 and ATG-16 were negative in the tumors, whereas beclin-1 was positive in four of five animals. In carcinoid patients, ATG-5 was negative in six of ten, ATG-16 negative in nine of ten, and beclin-1 negative in  three of ten patients. In cotton rats, ATG-5 and ATG-16 were negative in all tumors. Beclin-1 was negative in three of five rats. In INS-GAS mice, ATG-5 and beclin-1 were positive in the tumor area, but the numbers of immunopositive cells per gland were reduced by about 50% in comparison with wild-type mice. In adenocarcinoma patients, ATG-5 and ATG-16 were negative in eight of ten, and beclin-1 positive in all ten patients. Conclusions: An impaired autophagy took place at the stage of formation of ATG-5-ATG-12-ATG-16 complex in both gastric carcinoids and adenocarcinoma of both rodent models and patients. ATG-5 and ATG-16 might be better markers than beclin-1 in assessing autophagy in these lesions.




TÍTULO / TITLE:  - A large functioning parathyroid cyst in a patient with multiple endocrine neoplasia type 1.

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

REVISTA / JOURNAL:  - Endocr J. 2013 Feb 2.

AUTORES / AUTHORS:  - Tamiya H; Miyakawa M; Suzuki H; Takeshita A; Ohashi K; Usui T; Miura D; Takeuchi Y

INSTITUCIÓN / INSTITUTION:  - Division of Endocrinology, Toranomon Hospital Endocrine Center, Tokyo 105-8470, Japan.

RESUMEN / SUMMARY:  - A 62-year-old woman presented with a mass on the left side of the neck. Biochemical testing revealed primary hyperparathyroidism. Further, a prolactinoma was detected, and the patient’s son and daughter also had primary hyperparathyroidism, indicating that the patient had multiple endocrine neoplasia type 1 (MEN1). Neck ultrasonography revealed several cystic nodules (</=30 mm) that appeared to be adenomatous. After parathyroidectomy with autotransplantation, the largest cystic mass, in the left lower thyroid lobe, was pathologically diagnosed as a functioning parathyroid cyst, and all laboratory data returned to normal. On genetic analysis of blood, we found a novel single base insertion (duplication) in exon 10 codon 552 of the MEN1 gene (c1659dupT) that creates an early stop codon. This is the first case report of a parathyroid  cyst resulting from parathyroid hyperplasia in a MEN1 patient.




TÍTULO / TITLE:  - Pasireotide, a multi-somatostatin receptor ligand with potential efficacy for treatment of pituitary and neuroendocrine tumors.

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

REVISTA / JOURNAL:  - Drugs Today (Barc). 2013 Feb;49(2):89-103. doi: 10.1358/dot.2013.49.2.1915142.

            ●● Enlace al texto completo (gratuito o de pago) 1358/dot.2013.49.2.1915142

AUTORES / AUTHORS:  - Feelders RA; de Herder WW; Neggers SJ; van der Lely AJ; Hofland LJ

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands. r.feelders@erasmusmc.nl

RESUMEN / SUMMARY:  - Somatostatin receptors are an important target for medical treatment of pituitary and neuroendocrine tumors. To date, five somatostatin receptor (sst) subtypes have been identified. The currently available somatostatin analogues octreotide and lanreotide have predominantly affinity for sst. Pasireotide is a sst multireceptor ligand with affinity for sst, sst, sst and sst and this broader binding profile may translate into a higher efficacy with respect to suppression  of hormone production and cell growth in certain tumors. Experimental animal studies and in vitro studies with cultured tumor cells have shown that pasireotide strongly suppresses growth hormone and adrenocorticotropin production. In addition, pasireotide can influence tumor cell growth via effects  on apoptosis and angiogenesis. In this review, the role of somatostatin receptors in pituitary and neuroendocrine tumors is briefly discussed followed by an overview of possible applications of pasireotide based on recent trials in patients with acromegaly, Cushing’s disease and neuroendocrine tumors.




TÍTULO / TITLE:  - Hypermetabolic Mesenteric Brown Adipose Tissue on Dual-Time Point FDG PET/CT in a Patient With Benign Retroperitoneal Pheochromocytoma.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182816515

AUTORES / AUTHORS:  - Dong A; Wang Y; Lu J; Zuo C

INSTITUCIÓN / INSTITUTION:  - From the *Department of Nuclear Medicine, Changhai Hospital, Shanghai, China, daggerDepartment of Pathology, and double daggerDepartment of Radiology, Changhai Hospital, Shanghai, China.

RESUMEN / SUMMARY:  - Intense FDG uptake of the mesenteric brown adipose tissue (BAT) is rare. We present a case of benign retroperitoneal pheochromocytoma showing multiple hypermetabolic regions corresponding with common locations of BAT. Furthermore, the mesenteric region showed intense FDG uptake, with SUVmax of 10.6. FDG PET/CT  findings of this case supports the previous theories that the incidence of BAT may be higher in patients with pheochromocytoma than in patients without, and the intra-abdominal fat of human adults, including the omental fat, which is brown adipose tissue in infancy, becomes reactivated in the presence of high circulating noradrenaline concentrations.




TÍTULO / TITLE:  - INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors.

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

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Mar 22;432(4):586-92. doi: 10.1016/j.bbrc.2013.02.042. Epub 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.02.042

AUTORES / AUTHORS:  - Mashima H; Ohno H; Yamada Y; Sakai T; Ohnishi H

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. Electronic address: hmashima1-tky@umin.ac.jp.

RESUMEN / SUMMARY:  - Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5-RXFP4 signaling might play a role in  an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.




TÍTULO / TITLE:  - Depletion of the novel p53-target gene carnitine palmitoyltransferase 1C delays tumor growth in the neurofibromatosis type I tumor model.

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

REVISTA / JOURNAL:  - Cell Death Differ. 2013 Apr;20(4):659-68. doi: 10.1038/cdd.2012.168. Epub 2013 Feb 15.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cdd.2012.168

AUTORES / AUTHORS:  - Sanchez-Macedo N; Feng J; Faubert B; Chang N; Elia A; Rushing EJ; Tsuchihara K; Bungard D; Berger SL; Jones RG; Mak TW; Zaugg K

INSTITUCIÓN / INSTITUTION:  - Laboratory for Applied Radiation Oncology, Department of Radiation Oncology, University Hospital, Zurich, Switzerland.

RESUMEN / SUMMARY:  - Despite the prominent pro-apoptotic role of p53, this protein has also been shown to promote cell survival in response to metabolic stress. However, the specific mechanism by which p53 protects cells from metabolic stress-induced death is unknown. Earlier we reported that carnitine palmitoyltransferase 1C (CPT1C), a brain-specific member of a family of mitochondria-associated enzymes that have a  central role in fatty acid metabolism promotes cell survival and tumor growth. Unlike other members of the CPT family, the subcellular localization of CPT1C and its cellular function remains elusive. Here, we report that CPT1C is a novel p53-target gene with a bona fide p53-responsive element within the first intron.  CPT1C is upregulated in vitro and in vivo in a p53-dependent manner. Interestingly, expression of CPT1C is induced by metabolic stress factors such as hypoxia and glucose deprivation in a p53 and AMP activated kinase-dependent manner. Furthermore, in a murine tumor model, depletion of Cpt1c leads to delayed tumor development and a striking increase in survival. Taken together, our results indicate that p53 protects cells from metabolic stress via induction of CPT1C and that CPT1C may have a crucial role in carcinogenesis. CPT1C may therefore represent an exciting new therapeutic target for the treatment of hypoxic and otherwise treatment-resistant tumors.




TÍTULO / TITLE:  - Merkel Cell Polyomavirus Large T Antigen has Growth Promoting and Inhibitory Activities.

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

REVISTA / JOURNAL:  - J Virol. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1128/JVI.00385-13

AUTORES / AUTHORS:  - Cheng J; Rozenblatt-Rosen O; Paulson KG; Nghiem P; Decaprio JA

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

RESUMEN / SUMMARY:  - Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. In at least 80% of all MCC, Merkel cell polyomavirus (MCPyV) DNA has undergone clonal integration into the host cell genome and most tumors express the MCPyV large and small T antigens. In all cases of MCC reported to date, the integrated MCPyV genome has undergone mutations in large T antigen. These mutations result in expression of a truncated large T antigen that retains the Rb binding or LXCXE motif but deletes the DNA binding and helicase domains. However, it is not known  what are the transforming functions of full-length and truncated MCPyV large T antigen. We compared the transforming activities of full-length, truncated, as well as the alternatively spliced 57kT forms of MCPyV large T antigen. MCPyV large T antigen could bind to Rb but was unable to bind to p53. Furthermore, MCPyV truncated large T antigen was more effective than full-length and 57kT large T antigen in promoting the growth of human and mouse fibroblasts. In contrast, expression of the MCPyV large T antigen C-terminal 100 residues could inhibit the growth of several different cell types. These data imply that the deletion of the C-terminus of MCPyV large T antigen found in MCC serves not only  to disrupt viral replication but also results in the loss of a distinct growth inhibitory function intrinsic to this region.




TÍTULO / TITLE:  - A Rare Case of Neuroendocrine Tumor of the Middle Ear Detected by Gallium-68-DOTANOC-PET/CT.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-4046

AUTORES / AUTHORS:  - Treglia G; Baldelli R; Cristalli G; Visca P; Barnabei A; Rufini V; Appetecchia M

INSTITUCIÓN / INSTITUTION:  - Institute of Nuclear Medicine (G.T., V.R.), Catholic University, 00168 Rome, Italy; and Endocrinology Unit (R.B., A.B., M.A.), Department of Otolaryngology (G.C.), and Department of Pathology (P.V.), Regina Elena National Cancer Institute, 00144 Rome, Italy.

RESUMEN / SUMMARY:  - Abstract Not Available.




TÍTULO / TITLE:  - CD44 and OTP are strong prognostic markers for pulmonary carcinoids.

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-12-3078

AUTORES / AUTHORS:  - Swarts DR; Henfling ME; Van Neste L; van Suylen RJ; Dingemans AM; Dinjens WN; Haesevoets A; Rudelius M; Thunnissen E; Volante M; Van Criekinge W; Engeland M van; Ramaekers FC; Speel EJ

INSTITUCIÓN / INSTITUTION:  - Molecular Cell Biology, Maastricht University.

RESUMEN / SUMMARY:  - PURPOSE: Pulmonary carcinoids are well-differentiated neuroendocrine tumors showing usually a favorable prognosis. However, there is a risk for late recurrence and/or distant metastasis. Because histological classification in typical and atypical (AC) carcinoids is difficult and its reliability to predict  disease outcome varies, we evaluated three genes as potential prognostic markers, i.e., OTP, CD44 and RET. EXPERIMENTAL DESIGN: These genes were analyzed in 56 frozen carcinoids by quantitative RT-PCR. RET was further studied by methylation  and mutation analysis. Immunohistochemistry for CD44 and OTP protein expression was performed on 292 carcinoids. RESULTS: Low mRNA expression levels of CD44 (p=1.8e-5) and OTP (p=0.00054), and high levels of RET (p=0.025), were strongly associated with a low 20-year survival of carcinoid patients. High RET expression was not related to promoter hypomethylation or gene mutations. A direct link between gene expression and protein levels was confirmed for CD44 and OTP, but not for RET. Within all carcinoids as well as ACs, absence of CD44 protein was significantly associated with low 20-year survival (p=0.00014 and p=0.00013, respectively). The absence of nuclear OTP followed by complete loss of expression was also significantly associated with unfavorable disease outcome in all carcinoids (p=5.2-6). Multivariate analyses revealed that age at diagnosis, histopathology, stage and cytoplasmic OTP immunoreactivity were independent predictors of prognosis. CONCLUSIONS: Our study indicates that CD44 and OTP are strong indicators of poor outcome. We therefore argue for implementation of these markers in routine diagnostics in addition to histopathology to improve subclassification of pulmonary carcinoids into prognostically relevant categories.




TÍTULO / TITLE:  - Papillary thyroid microcarcinoma: clinical and pathological study of 321 cases.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:39-45.

AUTORES / AUTHORS:  - Dzepina D; Bedekovic V; Cupic H; Kruslin B

INSTITUCIÓN / INSTITUTION:  - University of Zagreb, “Sestre milosrdnice” University Clinical Hospital Center, Department of ENT - Head and Neck Surgery, Zagreb, Croatia. dzepina.davor@gmail.com

RESUMEN / SUMMARY:  - The primary aim of the study was to investigate microcarcinoma characteristics of aggressivity, multicentricity and metastasis. Though its features are not significantly different from those of other papillary carcinomas, the optimal therapeutic approach continues to be an issue of controversy, most notably appropriate surgical approach and indications for neck dissection. The study is retrospective analysis of 321 microcarcinoma cases, operated upon with total thyroidectomy, with or without neck dissection. These cases were compared to larger papillary cancers. We found that 35.1% tumors were aggressive; 25.2% were  multicentric, with foci in the contralateral lobe nearly twice as often as in the ipsilateral lobe; and 18.2% were metastatic. In comparison to groups of < or = 2  cm and < or = 3 cm, microcarcinomas were less aggressive, multicentric and metastatic. Male gender and age < 45 were unfavorable parameters. Multivariate analysis revealed contralateral lobe multicentricity and male gender as risk factors for metastasis. Although microcarcinoma demonstrated better characteristics than larger tumors, this subgroup behaves aggressively and should be approached cautiously.




TÍTULO / TITLE:  - Cognitive Impairment Associated With Carcinoid Syndrome.

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

REVISTA / JOURNAL:  - Ann Surg. 2013 Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e318288ff6d

AUTORES / AUTHORS:  - Pasieka JL; Longman RS; Chambers AJ; Rorstad O; Rach-Longman K; Dixon E

INSTITUCIÓN / INSTITUTION:  - *Department of Surgery, Division of General Surgery and Surgical Oncology, University of Calgary and Tom Baker Cancer Center, Calgary, Alberta, Canada daggerDepartment of Medicine, Division of Endocrinology, University of Calgary and Tom Baker Cancer Center, Calgary, Alberta, Canada double daggerDepartment of  Psychology, Foothills Hospital, Calgary, Alberta, Canada.

RESUMEN / SUMMARY:  - OBJECTIVES:: To evaluate the cognitive performance of patients with carcinoid syndrome (CS) compared with population norms and cancer patients with non-neuroendocrine (non-NET) liver metastases. BACKGROUND:: The release of serotonin into the systemic circulation from metastatic small bowel neuroendocrine tumors (SB NET) causes CS. Many patients with CS followed in a multidisciplinary NET clinic seemed to exhibit a unique cognitive impairment. Because serotonin is known to influence a range of cognitive function, the question arouse as to whether cognitive impairment is another manifestation of CS. METHODS:: Patients were recruited from the multidisciplinary NET and the hepatobilary cancer clinics at the cancer center. The CS group consisted of patients with proven SB NETs metastatic to liver; the cancer comparison group consisted of patients with liver metastases from non-NET cancer. All completed a  self-reported cognitive questionnaire and a battery of 6 standardized neurocognitive tests. Both groups were compared to age/sex/educational-matched norms. RESULTS:: Thirty-six patients with CS and 20 with non-NET metastases were  enrolled. Patients with CS reported greater cognitive dysfunction in all cognitive domains than both norms and the comparison cancer group. On cognitive testing, patients with CS demonstrated weakness in initiation, processing speed,  visual memory, cognitive efficiency, and delayed verbal recall compared with norms. Although the patients with non-NET cancer also demonstrated some cognitive dysfunction compared with norms, the patients with CS did significantly worse on  delayed recall (P = 0.03) and marginally slower on speeded mental flexibility (P  = 0.097) compared with patients with non-NET cancer. CONCLUSION:: This study confirmed our clinical observation that patients with CS suffer from cognitive impairment that is different from the non-NET cancer group and population norms.




TÍTULO / TITLE:  - Development of a novel electrochemical sensor using pheochromocytoma cells and its assessment of acrylamide cytotoxicity.

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

REVISTA / JOURNAL:  - Biosens Bioelectron. 2013 Jun 15;44:122-6. doi: 10.1016/j.bios.2013.01.031. Epub  2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bios.2013.01.031

AUTORES / AUTHORS:  - Sun X; Ji J; Jiang D; Li X; Zhang Y; Li Z; Wu Y

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Food Science and Technology, School of Food Science of Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address: sxlzzz@jiangnan.edu.cn.

RESUMEN / SUMMARY:  - We report on a sensitive, simple, label-free cell-based electrochemical sensor to monitor the toxic effect of acrylamide on the Pheochromocytoma cells. The surface of the electrode was modified with gold nanoparticles and electrochemically reduced graphene oxide. Cyclic voltammetry, impedance spectroscopy and differential pulse voltammetry were applied to characterize the modified electrode. Reduced graphene oxide was proved to increase electron-transfer rate between the cell and the surface of electrode, while gold nanoparticle retain cell bioactivity. The sensor exhibited good correlation to the logarithmic value  of cell numbers ranging from 1.6x10 to 1.6x10 cells mL, with R.S.D value of 1.68%. The value of differential pulse voltammetry (cell adsorption concentration of 1.6x10 cells mL) decreased with the concentration of acrylamide in range of 0.1-5mM with the detection limit as 0.04mM. Scanning electron microscope-based morphological and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis confirmed the results of the electrochemical study. This sensor was proved to be a useful tool for probing the toxicity of cells, and assisted in the development of a labeling-free, simple, rapid and immediate detection method.




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.




TÍTULO / TITLE:  - A case report of metastatic atypical thymic carcinoid with ectopic ACTH production: locoregional control after adaptive radiation treatment.

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

REVISTA / JOURNAL:  - Tumori. 2012 Nov;98(6):172e-5e. doi: 10.1700/1217.13516.

            ●● Enlace al texto completo (gratuito o de pago) 1700/1217.13516

AUTORES / AUTHORS:  - Valeriani M; Agolli L; Falco T; Osti MF; De Sanctis V; Enrici RM

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Sant’Andrea Hospital, Sapienza University, Rome, Italy.

RESUMEN / SUMMARY:  - Thymic carcinoid is an extremely rare malignancy. This tumor is often associated  with endocrine disorders such as Cushing’s syndrome, multiple endocrine neoplasia type 1 and superior vena cava syndrome. We describe the case of a 44-year-old Italian woman with metastatic atypical thymic carcinoid secreting ectopic adrenocorticotropic hormone who was treated with adaptive radiation therapy with  a curative dose schedule for a symptomatic mediastinal tumor. After 22 months, the patient was in good clinical condition, presenting stable disease without any evidence of local or systemic progression. To our knowledge there are no previously reported data regarding radical radiotherapy in the treatment of thymic carcinoids.




TÍTULO / TITLE:  - Changes in Energy Metabolism in Pheochromocytoma.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3625

AUTORES / AUTHORS:  - Petrak O; Haluzikova D; Kavalkova P; Strauch B; Rosa J; Holaj R; Brabcova Vrankova A; Michalsky D; Haluzik M; Zelinka T; Widimsky J Jr

INSTITUCIÓN / INSTITUTION:  - Third Department of Medicine (O.P., P.K., B.S., J.R., R.H., A.B.V., M.H., T.Z., J.W.), Department of Endocrinology and Metabolism, First Department of Surgery (D.M.), Department of Abdominal, Thoracic Surgery, and Traumatology, Institute of Sports Medicine (D.H.), and Institute of Medical Biochemistry and Laboratory Medicine (A.B.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague 2 128 08, Czech Republic.

RESUMEN / SUMMARY:  - Context:Catecholamine overproduction in pheochromocytoma affects basal metabolism, resulting in weight loss despite normal food intake.Objective:The objective of the study was to evaluate changes in energy metabolism expressed as  resting energy expenditure (REE) in patients with pheochromocytoma before and after adrenalectomy and the possible relationship with circulating inflammatory markers.Design:We measured REE in 17 patients (8 women) with pheochromocytoma by  indirect calorimetry (Vmax-Encore 29N system) before and 1 year after adrenalectomy. Body fat percentage was measured with a Bodystat device. Inflammatory markers (leukocytes count and C-reactive protein) and cytokines (TNF-alpha, IL-6, and IL-8) were analyzed with a Luminex 200.Results:REE measured in the pheochromocytoma group was 10.4% higher than the predicted value (1731 +/- 314 vs 1581 +/- 271 kcal/d; P = .004). Adrenalectomy significantly increased body mass index (P =0.004) and the percentage of body fat (P = .01), with a proportional increase in fat distribution (waist circumference, P = .045; hip circumference, P = .001). REE significantly decreased after adrenalectomy (1731 +/- 314 vs 1539 +/- 215 kcal/d; P = .002), even after adjustments in body surface and body weight (P < .001). After adrenalectomy, we found a significant decrease  in leukocyte counts (P = .014) and in the levels of TNF-alpha (P < .001), IL-6 (P = .048), and IL-8 (P = .007) but not C-reactive protein (P = .09). No significant correlations among calorimetry parameters, hormones, and proinflammatory markers  were detected.Conclusions:Chronic catecholamine overproduction in pheochromocytoma may lead to a proinflammatory and hypermetabolic state characterized by increased REE. Adrenalectomy leads to the normalization of energy metabolism followed by an increase in body mass index and body fat content and decreases in inflammatory markers and cytokines.




TÍTULO / TITLE:  - Is the excess cardiovascular morbidity in pheochromocytoma related to blood pressure or to catecholamines?

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar;98(3):1100-6. doi: 10.1210/jc.2012-3669. Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3669

AUTORES / AUTHORS:  - Stolk RF; Bakx C; Mulder J; Timmers HJ; Lenders JW

INSTITUCIÓN / INSTITUTION:  - MD, PhD, Department of Medicine, Division of General Internal Medicine, Radboud University Medical Center Nijmegen, Geert Grooteplein Zuid 8, 6525GA, Nijmegen, The Netherlands. j.lenders@aig.umcn.nl.

RESUMEN / SUMMARY:  - Background: It is generally accepted that pheochromocytoma is associated with an  increased cardiovascular risk. This is however not based on studies with an appropriate control group of patients with essential hypertension. Aim of the Study: We examined whether patients with pheochromocytoma have an excess cardiovascular morbidity as compared to hypertensive patients. Methods: In a retrospective case-control study we reviewed the medical charts of 109 pheochromocytoma patients for cardiovascular events within 5 years prior to the diagnosis. These patients were matched to control patients with essential hypertension for gender and year of birth and diagnosis. Outcome variables were ischemic heart disease, cerebrovascular accidents, and transient ischemic attacks. Classical cardiovascular risk factors were also assessed. Results: A significantly higher rate of patients with pheochromocytoma suffered a cardiovascular event (13.8%; 95% confidence interval: 7.9%-21.6%) as compared to  hypertensive patients (1.1%, 95% confidence interval: 0.1%-3.9%) (P < .001). Blood pressure level was lower in pheochromocytoma patients (153/91 +/- 35/15 mm  Hg) than in hypertensive patients (170/103 +/- 18/8 mm Hg) (P < .001), even after correction for use of antihypertensive medication (P < .02). The difference in event rates could not be attributed to differences in other cardiovascular risk factors. Conclusions: Pheochromocytoma patients have a clearly higher rate of cardiovascular events than patients with essential hypertension. This cannot be attributed to differences in blood pressure or other cardiovascular risk factors. The most likely explanation for the excess event rate is the prolonged exposure to the toxic effects of tumoral catecholamines. These data underpin the importance of a timely diagnosis and treatment of pheochromocytoma.




TÍTULO / TITLE:  - Radioembolization for treatment of liver metastases from neuroendocrine tumors: correlation with imaging and biomarkers.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar;42(2):358-60. doi: 10.1097/MPA.0b013e31825f4087.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31825f4087

AUTORES / AUTHORS:  - Ozao-Choy J; Friedman ML; Kim AS; Wachsman A; Wolin EM; Yu R; Nissen NN; Colquhoun SD

INSTITUCIÓN / INSTITUTION:  - Department of Surgery Cedars-Sinai Medical Center Los Angeles, CA Department of Radiology Cedars-Sinai Medical Center Los Angeles, CA Department of Surgery Cedars-Sinai Medical Center Los Angeles, CA Department of Radiology Cedars-Sinai  Medical Center Los Angeles, CA Department of Medicine Cedars-Sinai Medical Center Los Angeles, CA Department of Surgery Cedars-Sinai Medical Center Los Angeles, CA colquhouns@cshs.org.




TÍTULO / TITLE:  - Urapidil in the Preoperative Treatment of Pheochromocytomas: A Safe and Cost-effective Method.

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

REVISTA / JOURNAL:  - World J Surg. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00268-013-1933-9

AUTORES / AUTHORS:  - Habbe N; Ruger F; Bojunga J; Bechstein WO; Holzer K

INSTITUCIÓN / INSTITUTION:  - Department of General and Visceral Surgery, Hospital of the Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany, nils.habbe@kgu.de.

RESUMEN / SUMMARY:  - BACKGROUND: Surgery for pheochromocytoma may lead to uncontrolled catecholamine secretion with severe hypertension and cardiac failure. Perioperative alpha(1)-receptor-blockade with orally administered phenoxybenzamine or intravenous urapidil therefore is a standard procedure in the treatment regime prior to surgery. METHODS: Medical records of 30 patients who underwent surgery for pheochromocytoma during the years 2002-2011 were retrospectively analyzed. We investigated the difference in the clinical course of patients undergoing surgery for pheochromocytoma with either phenoxybenzamine or urapidil pretreatment with special regard to the intraoperative course and length of hospital stay and costs. RESULTS: Nineteen (16 female, 3 male) patients (63 %) received a preoperative alpha-block with orally administered phenoxybenzamine. Eleven patients (6 female, 5 male) (37 %) were treated with intravenous urapidil for 3 days prior to surgery. Intraoperative episodes of hypertension or hypotension did not differ significantly. The median total hospital stay in phenoxybenzamine-treated patients was 17 days in contrast to 11 days in the urapidil group (p = 0.0087). Patients who received i.v. pretreatment spent significantly fewer days in the hospital prior to operation [median: 3 days (range: 3-7 days) versus 9 days (range: 3-21 days); p = 0.0001]. The reduction in the number of days in the hospital in the urapidil group led to a significantly elevated revenue per day (<euro>637.49/day versus <euro>412.50/day; p = 0.001). CONCLUSIONS: Perioperative treatment with the selective alpha(1) blocker urapidil remains a simple and cost effective method in the treatment regime of patients with pheochromocytoma.




TÍTULO / TITLE:  - Misidentification of Putative Medullary Thyroid Cancer Cell Lines RO-H85-1 and RO-D81-1.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar;98(3):954-5. doi: 10.1210/jc.2012-4181.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-4181

AUTORES / AUTHORS:  - Dadon T; Ball D; Nelkin BD

INSTITUCIÓN / INSTITUTION:  - Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street,  Baltimore, Maryland 21287. bnelkin@jhmi.edu.




TÍTULO / TITLE:  - Unilateral and bilateral adrenalectomy for pheochromocytoma requires adjustment of urinary and plasma metanephrine reference ranges.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar;98(3):1076-83. doi: 10.1210/jc.2012-3418. Epub  2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3418

AUTORES / AUTHORS:  - Osinga TE; van den Eijnden MH; Kema IP; Kerstens MN; Dullaart RP; de Jong WH; Sluiter WJ; Links TP; van der Horst-Schrivers AN

INSTITUCIÓN / INSTITUTION:  - MD, PhD, Department of Endocrinology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. a.n.a.van.der.horst@umcg.nl.

RESUMEN / SUMMARY:  - Context: Follow-up after adrenalectomy for pheochromocytoma is recommended because of a recurrence risk. During follow-up, plasma and/or urinary metanephrine (MN) and normetanephrine (NMN) are interpreted using reference ranges obtained in healthy subjects. Objective: Because adrenalectomy may decrease epinephrine production, we compared MN and NMN concentrations in patients after adrenalectomy to concentrations in a healthy reference population. Design: A single-center cohort study was performed in pheochromocytoma patients after adrenalectomy between 1980 and 2011. Subjects: Seventy patients after unilateral and 24 after bilateral adrenalectomy were included. Main Outcome Measures: Plasma-free and urinary-deconjugated MN and NMN determined at 3 to 6 months and annually until 5 years after adrenalectomy were compared with concentrations in a reference population. Data are presented in median (interquartile range). Results: Urinary and plasma MN concentrations 3 to 6 months after unilateral adrenalectomy were lower compared with the reference population (39 [31-53] mumol/mol creatinine and 0.14 [0.09-0.18] nmol/L vs 61 [49-74] mumol/mol creatinine and 0.18 [0.13-0.23] nmol/L, respectively, both P <  .05). Urinary MN after bilateral adrenalectomy was reduced even further (7 [1-22] mumol/mol creatinine; P < .05). Urinary and plasma NMN were higher after unilateral adrenalectomy (151 [117-189] mumol/mol creatinine and 0.78 [0.59-1.00] nmol/L vs 114 [98-176] mumol/mol creatinine and 0.53 [0.41-0.70] nmol/L; both P < .05). Urinary NMN after bilateral adrenalectomy was higher (177 [106-238] mumol/mol creatinine; P < .05). Changes in urinary and plasma MNs persisted during follow-up. Conclusion: Concentrations of MN are decreased, whereas NMN concentrations are increased after unilateral and bilateral adrenalectomy. Adjusted reference values for MN and NMN are needed in the postsurgical follow-up of pheochromocytoma patients.




TÍTULO / TITLE:  - Promyelocytic leukemia zinc finger and histone H1.5 differentially stain low- and high-grade pulmonary neuroendocrine tumors: a pilot immunohistochemical study.

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

REVISTA / JOURNAL:  - Hum Pathol. 2013 Feb 14. pii: S0046-8177(12)00442-X. doi: 10.1016/j.humpath.2012.11.014.

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

AUTORES / AUTHORS:  - Hechtman JF; Beasley MB; Kinoshita Y; Ko HM; Hao K; Burstein DE

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Mount Sinai School of Medicine and Medical Center, New York, NY 10029. Electronic address: jaclyn.hechtman@mountsinai.org.

RESUMEN / SUMMARY:  - Promyelocytic leukemia zinc finger is a zinc finger transcription factor that functions as a transcriptional repressor. Its expression has been shown to be down-regulated in hematopoietic, melanocytic, and mesothelial malignancies. Histone H1.5 is a variant of histone H1, a family of linker proteins that organizes chromosomes into higher order structures. Its function is of key importance in gene expression and has been linked to more aggressive forms of prostatic carcinoma. This study aimed to investigate the immunohistochemical detectability of promyelocytic leukemia zinc finger and histone H1.5 in pulmonary neuroendocrine tumors, comprising 11 carcinoid tumorlets, 24 typical carcinoids,  12 atypical carcinoids, 20 small cell carcinomas, 11 large cell neuroendocrine carcinomas, and 2 combined small cell carcinomas-large cell neuroendocrine carcinomas. Promyelocytic leukemia zinc finger immunohistochemistry revealed moderate or strong nuclear staining in all carcinoid tumorlets, 23 of 24 typical  carcinoids, and 7 of 12 atypical carcinoids in contrast to 9 of 11 large cell neuroendocrine carcinomas, all small cell carcinoma, and both combined small cell carcinoma-large cell neuroendocrine carcinomas, which showed no nuclear immunoreactivity. Histone H1.5 immunohistochemistry revealed only focal or no immunoreactivity in all carcinoid tumorlets and 19 of 24 typical carcinoids, whereas 7 of 12 atypical carcinoids, 19 of 20 small cell carcinomas, 10 of 11 large cell neuroendocrine carcinomas, and both combined small cell carcinomas-large cell neuroendocrine carcinomas displayed positive (>/=10%) nuclear immunoreactivity-ranging from a minority of weak staining to a majority of strong staining cases. Our data suggest that the relative expression ratios of promyelocytic leukemia zinc finger and histone H1.5 may correlate with grade of pulmonary neuroendocrine tumors. Immunohistochemical stains for these markers, especially on small biopsies with crush artifact, may prove to be diagnostically  useful.




TÍTULO / TITLE:  - Paraganglioma of the Carotid Body: Treatment Strategy and SDH-gene Mutations.

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

REVISTA / JOURNAL:  - Eur J Vasc Endovasc Surg. 2013 Feb 19. pii: S1078-5884(13)00058-0. doi: 10.1016/j.ejvs.2013.01.018.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejvs.2013.01.018

AUTORES / AUTHORS:  - Fruhmann J; Geigl JB; Konstantiniuk P; Cohnert TU

INSTITUCIÓN / INSTITUTION:  - Department of Vascular Surgery, Medical University of Graz, Auenbruggerplatz 29,  8036 Graz, Austria. Electronic address: johanna.fruhmann@medunigraz.at.

RESUMEN / SUMMARY:  - OBJECTIVES: The aim of the present study was to review treatment results in patients with paraganglioma (PGL) of the neck presenting as carotid body tumour,  long-term follow-up and relevance of genetic testing for succinate dehydrogenase  (SDH)-gene mutations. DESIGN: Retrospective analysis of prospectively collected data and prospective genetic analysis. MATERIALS AND METHODS: Over a 25-year period (1987-2011) 50 patients were operated for 63 PGLs of the neck. Pre-, intra- and postoperative findings were analysed. Sanger sequencing was performed  for genetic testing of SDH-gene mutations (SDH B, SDHC and SDHD). RESULTS: Fifty  patients underwent resection of 63 PGLs (62 benign, one malignant) without mortality. Eight patients underwent preoperative embolisation. Vascular surgical  procedures were required in 15 operations (15/63 = 23.8%). Nerve lesions occurred after 13 operations (13/63 = 20.6%) and were associated with large tumours. A total of 44 patients are alive after a mean follow-up of 9.8 years. In 40 patients 17 SDH-gene mutations were detected (17/40 = 42.5%): 14 SDHD mutations,  two SDHB mutations and one rare SDHC mutation. CONCLUSION: Surgery for PGL is recommended. All PGL patients should be screened for SDH mutations because it impacts the individual follow-up strategy. Whereas all PGL patients require annual ultrasound control, mutation carriers and family members with proven mutations should in addition be regularly examined by magnetic resonance imaging  (MRI) of head, neck, thorax, abdomen and pelvis.




TÍTULO / TITLE:  - Achaete-scute homolog 1 as a marker of poorly differentiated neuroendocrine carcinomas of different sites: a validation study using immunohistochemistry and  quantitative real-time polymerase chain reaction on 335 cases.

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

REVISTA / JOURNAL:  - Hum Pathol. 2013 Jan 31. pii: S0046-8177(12)00441-8. doi: 10.1016/j.humpath.2012.11.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.11.013

AUTORES / AUTHORS:  - La Rosa S; Marando A; Gatti G; Rapa I; Volante M; Papotti M; Sessa F; Capella C

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Ospedale di Circolo, 21100 Varese, Italy. Electronic address: stefano.larosa@ospedale.varese.it.

RESUMEN / SUMMARY:  - Neuroendocrine carcinomas show overlapping morphological and immunohistochemical  features independently of their site of origin, which makes identification of the primary location problematic when they are diagnosed as metastases of unknown origin. Neuroendocrine carcinomas are easily morphologically differentiated from  neuroendocrine tumors in surgical material, although this distinction can be difficult when using small biopsy specimens. The diagnostic usefulness of different transcription factors as site-specific markers or as discriminating markers between neuroendocrine carcinomas and neuroendocrine tumors has been previously studied with sometimes contradictory results. In this respect, the role of achaete-scute homolog 1 has been poorly investigated, although some recent findings demonstrate its expression in neuroendocrine carcinomas. Using immunohistochemistry and quantitative real-time polymerase chain reaction, we investigated the expression of achaete-scute homolog 1 in 335 neuroendocrine neoplasms (194 neuroendocrine carcinomas and 141 neuroendocrine tumors) of different sites, to check its possible utility as diagnostic marker. High concordance between immunohistochemical and molecular findings was found. Achaete-scute homolog 1 expression was identified in 82% of lung neuroendocrine carcinomas and 70% of extrapulmonary neuroendocrine carcinomas. Achaete-scute homolog 1 was not detected in any gastroenteropancreatic neuroendocrine tumor and was found in only a minority of lung carcinoids. The diagnostic sensitivity and specificity of achaete-scute homolog 1 expression were 82.4% and 89.7% in distinguishing neuroendocrine carcinomas from neuroendocrine tumors of the lung,  40.6% and 100% to differentiate extrapulmonary neuroendocrine carcinomas from neuroendocrine tumors, and 82.4% and 59.4% in distinguishing lung from extrapulmonary neuroendocrine carcinomas. Our data suggest that achaete-scute homolog 1 is not a site-specific marker. However, achaete-scute homolog 1 may be  proposed as a diagnostic marker of poor differentiation and may help to differentiate neuroendocrine carcinomas from neuroendocrine tumors in difficult cases.




TÍTULO / TITLE:  - Brain carcinoid metastases: outcomes and prognostic factors.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Apr;118(4):889-95. doi: 10.3171/2013.1.JNS121556. Epub 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.JNS121556

AUTORES / AUTHORS:  - Mallory GW; Fang S; Giannini C; Van Gompel JJ; Parney IF

INSTITUCIÓN / INSTITUTION:  - Departments of Neurologic Surgery and.

RESUMEN / SUMMARY:  - Object Carcinoid tumors are rare and have generally been regarded as indolent neoplasms. Systemic disease is often incurable; however, patients may live years  with this disease. Furthermore, metastatic brain lesions are extremely uncommon.  As such, few series have examined outcomes and prognostic factors in those with brain involvement. Methods The authors performed a retrospective review of patients who underwent primary treatment at Mayo Clinic in Rochester, Minnesota,  for metastatic carcinoid tumors to the brain between 1986 and 2011. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier statistics. Cox proportional hazards were used to determine predictors of survival. Results Fifteen patients underwent primary treatment for  metastatic carcinoid tumors to the brain between 1986 and 2011. Their mean age was 58 +/- 12 years. Eighty percent (n = 12) of patients underwent surgery, whereas 2 received stereotactic radiosurgery and 1 had whole-brain radiation therapy (WBRT) as the primary treatment. The median follow-up duration was 19 months (maximum 124 months). Systemic disease progression occurred in 73% and was the leading cause of death in known cases, while intracranial disease recurred in 40%. The median PFS and OS were 21 and 19 months, respectively. The use of adjuvant WBRT correlated with improved PFS (HR 0.15, CI 0.0074-0.95, p = 0.044).  Those who underwent surgery as primary modalities trended toward longer progression-free intervals (p = 0.095), although this did not reach significance. Conclusions Metastatic carcinoid disease to the brain appears to have a worse prognosis than that of other extracranial metastases. Although there was a trend  toward a survival advantage in patients who underwent surgery and WBRT, further study is needed to establish definitive treatment recommendations.




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.




TÍTULO / TITLE:  - Improving the Diagnosis and Management of Neuroendocrine Tumors: Utilizing New Advances in Biomarker and Molecular Imaging Science.

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

REVISTA / JOURNAL:  - Neuroendocrinology. 2013 Feb 23.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000348832

AUTORES / AUTHORS:  - Giandomenico V; Modlin I; Ponten F; Nilsson M; Landegren U; Bergqvist J; Khan M; Millar R; Langstrom B; Borlak J; Eriksson B; Nielsen B; Baltzer L; Waterton JC; Ahlstrom H; Oberg K

INSTITUCIÓN / INSTITUTION:  - Department of Medical Sciences, Endocrine Oncology, University Hospital, Uppsala, Sweden.

RESUMEN / SUMMARY:  - Neuroendocrine tumors (NET) are malignant solid tumors that arise in hormone secreting tissue of the diffuse neuroendocrine system or endocrine glands. Although traditionally understood to be a rare disease, the incidence and prevalence of NET has increased greatly in the past three decades. However, during this time progress in diagnosis and outcome of NET has generally been modest. In order to achieve improved outcome in NET, a better understanding of NET biology, along with more reliable serum markers and better techniques to identify tumor localization and small lesions are needed. Although some NET biomarkers exist, sensitive and specific markers that predict tumor growth and behavior are generally absent. In addition, the integration of new molecular imaging technologies in patient diagnosis and follow up has the potential to enhance care. To discuss developments and issues required to improve diagnostics  and management of patients with NET, with specific focus on the latest advances in molecular imaging and biomarker science, 17 global leaders in the fields of NET, molecular imaging and biomarker technology gathered to participate in a 2-day meeting hosted by Professor Kjell Oberg at the University of Uppsala, Uppsala, Sweden. During this time, findings were presented regarding methods with potential prognostic and treatment applications in NET or other types of cancers. This manuscript describes the symposium presentations and resulting discussions.




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.




TÍTULO / TITLE:  - Local bystander effect induces dormancy in human medullary thyroid carcinoma model in vivo.

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

REVISTA / JOURNAL:  - Cancer Lett. 2013 Feb 26. pii: S0304-3835(13)00166-3. doi: 10.1016/j.canlet.2013.02.040.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.040

AUTORES / AUTHORS:  - Kucerova L; Feketeova L; Matuskova M; Kozovska Z; Janega P; Babal P; Poturnajova M

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular Oncology, Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovakia. Electronic address: exonkuce@savba.sk.

RESUMEN / SUMMARY:  - The extent of local bystander effect induced by fusion yeast cytosine deaminase::uracil phosphoribosyltransferase (yCD) in combination with 5-fluorocytosine (5FC) was evaluated in xenogeneic model of human medullary thyroid carcinoma (MTC). This approach to gene-directed enzyme/prodrug therapy (GDEPT) induces strong bystander cytotoxicity. Effector yCD-TT mixed with target  EGFP-TT cells in a ratio 2:9 could achieve significant tumor regression and 14-fold decrease in serum marker calcitonin upon 5FC administration. Histopathological analysis unraveled that antitumor effect resulted in tumor dormancy and proliferation arrest of remaining tumor cell clusters in vivo. yCD/5FC combination represents another GDEPT approach to achieve tumor growth control in MTC.




TÍTULO / TITLE:  - Clinical outcomes of atypical carcinoid tumors of the lung and thymus: 7-year experience of a rare malignancy at single institute.

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

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):479. doi: 10.1007/s12032-013-0479-x. Epub 2013 Feb 3.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0479-x

AUTORES / AUTHORS:  - Han B; Sun JM; Ahn JS; Park K; Ahn MJ

INSTITUCIÓN / INSTITUTION:  - Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea. hborbor@naver.com

RESUMEN / SUMMARY:  - Atypical carcinoid tumors above the diaphragm are extremely rare and are associated with unfavorable clinical outcomes compared to typical carcinoid tumors. We described various clinical and histological features and investigated  outcomes in patients with atypical carcinoid tumor of the lung and thymus. Medical records were reviewed in patients diagnosed with atypical carcinoid tumor of the lung or thymus at Samsung Medical Center between December 2003 and April 2010. We reviewed patient characteristics and treatment modalities and analyzed patient outcome in terms of disease-free survival and overall survival. Of the nineteen study patients, there were twelve patients with atypical carcinoid tumors of the lung and seven patients with thymic ones. All patients except one underwent complete resection as the main treatment. All patients who had tumors with lesser mitoses (</=5/10 high-power fields) are presently alive; moreover, they are all free of recurrence except for one patient who is also alive with recurrent tumor without any palliative treatment. Distant metastasis after curative resection developed in six patients and two of them died of progressive  disease 25-31 months after recurrence even after palliative systemic chemotherapy. Atypical carcinoid tumor of the lung and thymus was a malignant disease that was prone to metastasize to distant sites even after curative resection and adjuvant treatment. Number of mitosis was a predicting factor for recurrence of disease and death in patients with atypical carcinoid tumor of the  lung and thymus.




TÍTULO / TITLE:  - Overexpression of the Insulin-like growth factor 1 receptor (IGF-1R) is associated with malignancy in familial pheochromocytomas and paragangliomas.

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

REVISTA / JOURNAL:  - Clin Endocrinol (Oxf). 2013 Mar 18. doi: 10.1111/cen.12205.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cen.12205

AUTORES / AUTHORS:  - Fernandez MC; Martin A; Venara M; Calcagno ML; Sanso G; Quintana S; Chemes HE; Barontini M; Pennisi PA

INSTITUCIÓN / INSTITUTION:  - Centro de Investigaciones Endocrinologicas, CEDIE-CONICET. Hospital de Ninos Dr.  R. Gutierrez, Gallo 1360 C1425EFD, Buenos Aires, Argentina.

RESUMEN / SUMMARY:  - CONTEXT: Pheochromocytomas and paragangliomas (pheo/pgl) are neuroendocrine tumors derived from chromaffin cells. Although mostly benign, up to 26% of pheo/pgl will undergo malignant transformation. Reliable histological signs to differentiate benign pheo/pgl from malignant tumors are currently lacking. Increased IGF-1R expression has been shown during progression to metastatic phenotypes of several types of cancer. OBJECTIVE: to analyze the distribution and expression of the IGF-1R in pheo/pgl of different genetic origin and degree of malignancy. MEASUREMENTS: we studied the expression of the IGF-1R protein by immunohistochemistry, in 40 primary tumors from patients with pheo/pgl from different genetic etiology (11/29 metastatic/non-metastatic disease). Results: We found a strong association between increased expression of IGF-1R and malignant behavior regardless the age at diagnosis and the genetic etiology. IGF-1R labeling was mostly weak in primary tumors from patients with non-metastatic pheo/pgl. Conversely, intense IGF-1R labeling was predominant in cases of pheo/pgl with confirmed metastatic disease. The risk of metastases was 11.7 times higher if tumor IGF-1R labeling was intense independently of age at diagnosis. The probability of remaining free of metastases was higher in patients with pheo/pgl scored weak for IGF-1R at 60 months and more than two fold higher at 120 months of follow-up than in patients with intense IGF-1R labeling in their primary tumors. CONCLUSIONS: Our results strongly suggest that IGF-1R is associated with malignancy in familial pheo/pgl and that IGF-1R expression in the primary tumor might be a useful tool to detect those patients harboring pheo/pgl  that have an increased risk of metastasis. © 2013 Blackwell Publishing Ltd.




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


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.




TÍTULO / TITLE:  - PAX8-PPARgamma oncogene in follicular thyroid tumors: RT-PCR and immunohistochemical analyses.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:79-82.

AUTORES / AUTHORS:  - Pauzar B; Karner I; Glavas-Obrovac L; Stefanic M; Dmitrovic B

INSTITUCIÓN / INSTITUTION:  - “J. J. Strossmayer” University, Osijek University Hospital Center, Department of  Clinical Cytology, Osijek, Croatia. pauzar.biljana@kbo.hr

RESUMEN / SUMMARY:  - US-guided fine needle aspiration cytology is currently the best diagnostic tool for thyroid nodules. However, it is not sensitive and specific enough for differentiating between benign and malignant follicular tumors. A potentially useful marker for this differentiation is the PAX8-PPARgamma rearrangement, identified in follicular thyroid carcinomas, but not in follicular adenomas or other types of thyroid tumors. The aim of this research was to determine the clinical significance of the PAX8-PPARgamma oncogene in diagnostics follicular thyroid tumors. The study included 62 patients with follicular or Hurthle cell tumors. Gene expression was determined by reverse transcription-polymerase chain  reaction (RT-PCR) from paraffin embedded tissues, and PCR products were checked using the agarose gel electrophoresis. The immunohistochemical analysis was performed on archive paraffin embedded tissues with the monoclonal PPARgamma antibody. The statistical analysis has indicated that neither the expression of PAX8-PPARgamma mRNA, nor the immunohystochemical analysis with the PPARgamma antibody correlate with the patohystological diagnosis. The oncogene, PAX8-PPARgamma has not met the expectations as a reliable tumor marker for differentiation between benign and malignant thyroid tumors, which makes the only reliable histological criteria—capsular and vascular invasion.




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.




TÍTULO / TITLE:  - Neuroendocrine Tumor in Liver With Positive ACTH Receptor: A Case Report.

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

REVISTA / JOURNAL:  - J Pediatr Hematol Oncol. 2013 Mar 21.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e318286d2ba

AUTORES / AUTHORS:  - Zein ME; Vali R; Charron M; Manson D; Perlman K; Shammas A

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Imaging, Division of Nuclear Medicine, The Hospital for  Sick Children, University of Toronto, Toronto, ON, Canada.

RESUMEN / SUMMARY:  - A rare case of possible primary ectopic adrenocorticotropic hormone (ACTH)-producing tumor in the liver mimicking a liver hemangioma is reported. A 9-year-old boy, with Cushing syndrome, was referred for the assessment of ectopic ACTH-producing tumor. Ultrasound, CT scan, and MRI of the abdomen revealed a liver lesion suggestive of a hemangioma. In-octreotide scintigraphy revealed focal activity in the liver, indicative of a somatostatin-positive lesion. Tc-labeled RBC scintigraphy was negative for hemangioma. After surgical resection of the tumor, the cortisol level converted to a normal range indicative of a rare possible primary ACTH-producing tumor in the liver, which was confirmed by histopathology.




TÍTULO / TITLE:  - POU domain transcription factor BRN2 is crucial for expression of ASCL1, ND1 and  neuroendocrine marker molecules and cell growth in small cell lung cancer.

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

REVISTA / JOURNAL:  - Pathol Int. 2013 Mar;63(3):158-68. doi: 10.1111/pin.12042.

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

AUTORES / AUTHORS:  - Ishii J; Sato H; Sakaeda M; Shishido-Hara Y; Hiramatsu C; Kamma H; Shimoyamada H; Fujiwara M; Endo T; Aoki I; Yazawa T

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama; Department of Pathology, Kyorin University School of Medicine, Mitaka.

RESUMEN / SUMMARY:  - BRN2 is a developmental neural cell-specific POU domain transcription factor and  is crucial for cell lineage determination. We investigated the importance of BRN2 in the expression of the lineage-specific transcription factors (achaete-scute homolog-like 1 (ASCL1) and NeuroD1 (ND1)) and neural/neuroendocrine marker molecules (neural cell adhesion molecule 1 (NCAM1), synaptophysin (SYP) and chromogranin A (CHGA)) in small cell lung cancer (SCLC) using cultured lung cancer cells. All examined SCLC cell lines expressed BRN2, as well as ASCL1, ND1, NCAM1, SYP and CHGA. The expression levels of ASCL1, ND1, NCAM1, SYP and CHGA considerably decreased when BRN2 was knocked down in SCLC cells, and the addition of a BRN2 transgene into non-SCLC (NSCLC) cells induced the expression of ASCL1,  ND1, NCAM1, SYP and CHGA. However, the BRN2 gene was not activated by the forced  expression of ASCL1 or ND1 in NSCLC cells. The knockdown of BRN2 caused significant growth retardation with decrease of S to G2 phase population and mitotic cell rates and unaltered Ki-67-labeled or apoptotic cell rates in SCLC cells, indicating increase of G1 phase population. These findings suggest that BRN2 is a higher level regulator than ASCL1 and ND1 and BRN2 might be involved in aggressiveness of SCLC.




TÍTULO / TITLE:  - Primary renal carcinoid: Treatment and prognosis.

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

REVISTA / JOURNAL:  - Crit Rev Oncol Hematol. 2013 Mar 8. pii: S1040-8428(13)00046-2. doi: 10.1016/j.critrevonc.2013.02.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.critrevonc.2013.02.003

AUTORES / AUTHORS:  - Korkmaz T; Seber S; Yavuzer D; Gumus M; Turhal NS

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey. Electronic address: taner.korkmaz@gmail.com.

RESUMEN / SUMMARY:  - Primary carcinoid tumors of the kidney are very rare, malignant tumors consisting of neuroendocrine cells. The pathogenesis of renal carcinoid is unclear because neuroendocrine cells are not normally found in adult renal parenchyma. Electron microscopy, immunohistochemistry, octreotide scan, positron emission tomography along with conventional radiographic imaging techniques are used in diagnosis and follow-up. Presenting symptoms usually include flank pain and haematuria. Early stage disease is treated with surgery only. However, randomized trials are lacking because of the very low number of reported cases. Thus, the role of debulking surgery, chemotherapy, radiotherapy, octreotide and targeted therapy in the management of advanced disease remains an open question. In this article the  clinicopathologic features and prognosis of this very rare disease along with treatment outcomes of the reported cases are reviewed. In addition, we report a new case of a metastatic primary renal atypical carcinoid tumor treated with octreotide therapy.




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


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.




TÍTULO / TITLE:  - Systemic therapeutic options for carcinoid.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):84-99. doi: 10.1053/j.seminoncol.2012.11.003.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.003

AUTORES / AUTHORS:  - Pavel M; Kidd M; Modlin I

INSTITUCIÓN / INSTITUTION:  - Charite University Medicine, 13353 Berlin, Germany. marianne.pavel@charite.de

RESUMEN / SUMMARY:  - “Carcinoids” are mostly slow-growing neuroendocrine neoplasms (NENs) with low proliferative activity. A wide range of therapeutic options with variable efficacy exist, including locoregional ablative strategies. Thereafter, some patients may not require medical therapy for years depending on the rate of progression or recurrence. However, the majority of patients require systemic treatment and therein lies the dilemma, since no antiproliferative agent is currently approved for carcinoids. Somatostatin analogs (SSAs), and to a lesser extent interferon-alpha, are standard therapy for carcinoids associated with the  carcinoid syndrome. These drugs have some antiproliferative efficacy. SSAs rarely lead to tumor remission but may modestly prolong time to tumor progression. Chemotherapy is of limited value in carcinoids with low proliferation indices but may be useful in higher grade tumors. Peptide receptor-targeted radionuclide therapy may be of benefit and is mostly used after medical therapies fail. However, it is considered an investigational modality. More recently, targeted drugs such as mammalian target of rapamycin (mTOR) inhibitors and anti-angiogenics have been investigated. Objective remissions are rare. Their value remains to be rigorously elucidated. Increased efficacy requires a better understanding of the underlying tumor biology and identification of molecular pathological criteria to allow appropriate preselection of candidates for targeted therapies.




TÍTULO / TITLE:  - Anesthetic management for resection of hepatic paraganglioma metastatic from the  donor organ in an orthotopic liver transplant recipient: a case report.

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

REVISTA / JOURNAL:  - Transplant Proc. 2013 Mar;45(2):817-9. doi: 10.1016/j.transproceed.2012.10.043.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.transproceed.2012.10.043

AUTORES / AUTHORS:  - Sharma S; Wray C; Nourmand H

INSTITUCIÓN / INSTITUTION:  - University of California-Los Angeles, Los Angeles, California, USA. Electronic address: shasharma@mednet.ucla.edu.

RESUMEN / SUMMARY:  - This is a case report of the anesthetic management for the hepatic resection of a metastatic paraganglioma in a patient with a history of prior orthotopic liver transplantation. Of interest, the metastatic paraganglioma originated from the donor organ. The patient is an 80-year-old woman with multiple medical problems including a history of cryptogenic cirrhosis who underwent successful orthotopic  liver transplantation 9 years prior. She later presented with signs and symptoms  of catecholamine excess suggestive of a catecholamine-producing tumor (paraganglioma or pheochromocytoma). Elevated urine catecholamine levels and radiographic evidence of a paraganglioma in the transplanted liver metastatic from the donor organ confirmed the diagnosis. Radiofrequency ablation of the tumor and surgical resection was previously attempted without success. We describe the anesthetic management for the successful resection of the metastatic hepatic paraganglioma, which was complicated by profound intraoperative hypertension and hypotension that necessitated the use of multiple vasoactive infusions, extensive surgical blood loss requiring blood transfusion, and difficult glycemic control in an insulin-dependent diabetic patient. The postoperative course is also described. This unique case presented the anesthesia team with challenges specific to both surgery for hepatic resection as well as for catecholamine-secreting tumors. We are not aware of any reports of paragangliomas of either donor or recipient origin involving a transplanted liver, making this the first such report to the best of our knowledge.




TÍTULO / TITLE:  - Merkel cell carcinoma with divergent differentiation: histopathological and immunohistochemical study of 15 cases with PCR analysis for Merkel cell polyomavirus.

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

REVISTA / JOURNAL:  - Histopathology. 2013 Apr;62(5):711-22. doi: 10.1111/his.12091.

            ●● Enlace al texto completo (gratuito o de pago) 1111/his.12091

AUTORES / AUTHORS:  - Martin B; Poblet E; Rios JJ; Kazakov D; Kutzner H; Brenn T; Calonje E

INSTITUCIÓN / INSTITUTION:  - Dermatopathology Department, St John’s Institute of Dermatology, St Thomas’ Hospital, London, UK.

RESUMEN / SUMMARY:  - AIMS: To report on 15 cases of Merkel cell carcinoma (MCC) with divergent differentiation, to characterize its clinicopathological spectrum and its relationship with Merkel cell polyomavirus (MCV). METHODS AND RESULTS: Fifteen patients with a mean age of 81 years were included. Follow-up was available for 13 cases (range 12 days to 6 years; median 6 months). Recurrence, metastasis and  mortality rates were 15.4%, 53.8% and 61.5%, respectively. All tumours showed the typical histological and immunohistochemical features of MCC, with at least one additional divergent component. Eight cases had a single aberrant component (squamous in six cases, follicular in one case, and porocarcinoma in one case), six cases had two aberrant components (squamous and sarcomatous in three cases, glandular and squamous in two cases, and sarcomatous and neuroblastic in one case), and one case had three aberrant components (glandular, squamous, and sarcomatous). All cases had dysplastic changes in the overlying epithelium, and four of 15 showed epidermotropism. PCR analysis for Merkel cell polyomavirus (MCV) gave negative results in all 12 cases tested. CONCLUSIONS: Merkel cell carcinoma with divergent differentiation is a highly aggressive tumour that might be difficult to recognize, owing to its wide histological variability. Negativity for MCV suggests that the virus is not implicated in the development of this subtype of MCC.




TÍTULO / TITLE:  - Acute upper extremity arterial thrombosis and stroke in an unresected pheochromocytoma.

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

REVISTA / JOURNAL:  - J Vasc Surg. 2013 Mar 7. pii: S0741-5214(13)00092-X. doi: 10.1016/j.jvs.2012.12.058.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jvs.2012.12.058

AUTORES / AUTHORS:  - Kaiser S; Chronakos J; Dietzek AM

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Danbury Hospital, Danbury, Conn.

RESUMEN / SUMMARY:  - Pheochromocytoma is a rare cause of hypertension in the general population. Only  isolated reports show an association with acute obstructive arterial thrombosis.  A 50-year-old chronically noncompliant woman with a known unresected pheochromocytoma presented to the emergency department with ataxia. Imaging confirmed a right-sided ischemic stroke. During her hospital stay, the patient developed signs consistent with acute right upper extremity ischemia resulting from occlusion in the distal right subclavian, axillary, and proximal brachial arteries. Emergent open thrombectomy was successfully performed. In patients with an unresected pheochromocytoma, one must consider acute arterial thrombosis as a  rare but potentially limb-threatening and even life-threatening complication.




TÍTULO / TITLE:  - Skip metastases in papillary thyroid cancer.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:59-62.

AUTORES / AUTHORS:  - Kliseska E; Makovac I

INSTITUCIÓN / INSTITUTION:  - University of Zagreb, Zagreb University Hospital Centre, Department of Otorhinolaryngology and Head and Neck Surgery, Zagreb, Croatia. kliseska_elena@yahoo.com

RESUMEN / SUMMARY:  - Papillary thyroid carcinoma (PTC) is the most common malignant thyroid disease characterized by a high rate of cervical metastases (30-80%), especially due to paratracheal lymph node involvement. “Skip metastasis” are defined as a lateral lymph node metastasis without central lymph node involvement. The aim of this prospective study was to establish the lateral nodal metastasis pattern according to neck level, general occurrence and significance of skip metastasis in PTC. Forty-two previously untreated patients who presented between 2007 and 2011 with  concomitant diagnosis of papillary thyroid cancer and metastatic disease of the lateral neck, underwent total thyroidectomy and central and lateral neck dissection. Skip metastases were encountered in 8 (19.5%) patients, four female and four male, with a mean age of 43.3 years. In all patients with lateral skip metastasis, level III nodes were most frequently involved (75%) followed by level IV (50%), while no metastatic disease was found in level IIb. Based on our research, skip metastasis are not uncommon (a lateral lymph node metastasis without central lymph node involvement) and present in approximately 1/5 of PTC patients with cervical lymph node metastasis.




TÍTULO / TITLE:  - Thyroid metastasis from breast carcinoma resembling medullary thyroid carcinoma.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:63-6.

AUTORES / AUTHORS:  - Slipac J; Janjanin S; Ljepava D; Hutinec Z; Bence-Zigman Z

INSTITUCIÓN / INSTITUTION:  - University of Zagreb, Zagreb University Hospital Center, University Department of Head and Neck Surgery, Zagreb, Croatia. jslipac@gmail.com

RESUMEN / SUMMARY:  - We are reporting a case of a 42-yr-old female with a history of right breast carcinoma. She was surgically treated (breast quadrantectomy with axillary dissection) and receiving a third cycle of adjuvant chemotherapy when a feeling of a constant pressure in the front of the neck and lack of air occurred. Subsequent work-up revealed a node in the right thyroid lobe with enlarged paratracheal bilateral and right mid and lower jugular lymph nodes. Fine-needle aspiration cytology, repeated within a 20 days window and analyzed by two different cytologists, showed a medullary thyroid carcinoma with a cervical lymph nodes metastasis so the patient underwent total thyroidectomy with selective and  paratracheal neck dissection. Histology and immunohistochemistry revealed the specimen to be metastasis of breast carcinoma. During regular follow-up of our patient, eighteen months after initial diagnosis, no new metastases were found. To our best knowledge, this is the first described case of a thyroid metastasis of breast carcinoma that was cytologically misdiagnosed as a medullary thyroid carcinoma.




TÍTULO / TITLE:  - Lung parenchymal invasion in pulmonary carcinoid tumor: An important histologic feature suggesting the diagnosis of atypical carcinoid and poor prognosis.

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

REVISTA / JOURNAL:  - Lung Cancer. 2013 Feb 2. pii: S0169-5002(13)00012-3. doi: 10.1016/j.lungcan.2013.01.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.005

AUTORES / AUTHORS:  - Ha SY; Lee JJ; Cho J; Hyeon J; Han J; Kim HK

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Republic of Korea.

RESUMEN / SUMMARY:  - The majority of previous studies on pulmonary carcinoid tumor have usually focused on clinical behavior or outcome, seldom considering histopathologic features. We retrospectively collected 63 cases of resected pulmonary carcinoid tumors from 1995 to 2011 at Samsung Medical Center, Seoul, Korea. The clinical and pathological features were correlated and survival analyses were performed. Forty cases (63.5%) were classified as typical carcinoid (TC) and 23 cases (36.5%) were classified as atypical carcinoid (AC) according to WHO classification criteria. AC patients showed a higher frequency of current smoking status and a higher stage of the tumor by the American Joint Committee on Cancer  than TC patients. The disease was associated with death and recurrence in five and seven patients, respectively, with almost all of the associations found in AC patients. The five-year survival rate of TC and AC were 100% and 83.5%, respectively, with AC showing poorer prognosis than TC in overall survival (OS) and disease free survival (DFS) (p=0.005 and p=0.002). Lung parenchymal invasion  was observed more commonly in AC than in TC (39.1% vs 12.5%, p=0.01) and was a poor prognostic factor in OS and DFS. Rosette-like arrangements were found only in six cases of AC, while abundant basophilic cytoplasm mimicking paraganglioma and ossification were found only in TC. Through the comprehensive study of pulmonary carcinoid tumor in Korea, we suggest that lung parenchymal invasion could be a useful histologic feature to suspect the diagnosis of AC in daily practice as well as to predict the prognosis of carcinoid tumor.




TÍTULO / TITLE:  - Commentary: Merkel cell carcinoma: bridging the gap.

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

REVISTA / JOURNAL:  - Dermatol Surg. 2013 Feb;39(2):239. doi: 10.1111/dsu.12003.

            ●● Enlace al texto completo (gratuito o de pago) 1111/dsu.12003


INSTITUCIÓN / INSTITUTION:  - Beer Dermatology, University of Miami, West Palm Beach, Florida, USA. kenbeer@aol.com




TÍTULO / TITLE:  - The genetics of neuroendocrine tumors.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):37-44. doi: 10.1053/j.seminoncol.2012.11.005.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.005


INSTITUCIÓN / INSTITUTION:  - Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden. kjell.oberg@medsci.uu.se

RESUMEN / SUMMARY:  - Neuroendocrine tumors (NETs) present a wide spectrum of malignant diseases from rather benign to very malignant variants. The majority of these tumors are sporadic, but there are several familial (inherited) syndromes to consider, such  as multiple endocrine neoplasia type 1 and type 2 (MEN-1 and MEN-2), von Hippel-Lindau syndrome (VHL), tuberosclerosis, and neurofibromatosis syndromes. The MEN-1 gene is mutated not only in MEN-1 families, but a recent study shows that more than 40% of sporadic pancreatic NETs (PNETs) harbor MEN-1 gene mutations. The same study reported that ATRX/DAXX genes are mutated in a significant number of tumors, as are genes encoding components of the mammalian target of rapamycin (mTOR) signal transduction pathway. These findings have implications for the new therapies that have been approved for the treatment of PNETs, such as the tyrosine kinase inhibitor sunitinib, as well the mTOR inhibitor everolimus. Small intestinal NETs show a less varied mutational pattern in that the majority of genetic alterations are found on chromosome 18. There seem to be no differences between the sporadic and the familiar type of small intestinal NETs (carcinoids). A wide range of genetic alterations have been described for the different subtypes of NETs, but the mechanisms underlying tumor development are essentially unknown except for MEN-2, in which an activating mutation of the RET proto-oncogene drives tumor progression and affords a direct  genotype/phenotype correlation. Genome-wide screening of different types of NETs  can now be performed for a reasonable price and is likely to generate new insights into the tumor biology and carcinogenesis in various subtypes of NETs.




TÍTULO / TITLE:  - Importance of measurement of thyroglobulin and anti-thyroglobulin antibodies in differentiated thyroid cancer.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:33-8.

AUTORES / AUTHORS:  - Alagic-Smailbegovic J; Kucukalic-Selimovic E; Setic I; Becirovic M; Begovic L

INSTITUCIÓN / INSTITUTION:  - Clinical Center University of Sarajevo, Clinic of Otorhinolaryngology, Sarajevo,  Bosnia and Herzegovina. j.alagic@gmail.com

RESUMEN / SUMMARY:  - Differentiated thyroid cancers include papillary and follicular carcinomas, both  originating from follicular epithelium. Treatment of choice is usually total or near total thyroidectomy, followed by ablative radioiodine 131I treatment, and by the long-term administration of thyroid hormone. Despite its excellent prognosis, recurrent disease does occur in approximately 20-40% of patients. Guidelines for  the follow-up management of differentiated thyroid cancer are commonly based on circulating thyrogobulin measurement in the complete absence of eutopic thyroid tissue. A retrospective review was conducted on 116 patients (66 papillary and 50 follicular carcinoma, mean age 51.2 years) who had undergone total or near total  thyroidectomy and radioactive iodine remnant ablation. Serum thyroglobulin (Tg) and anti-thyroglobulin antibodies (TgAb) levels were measured preoperatively, 1 month after thyroidectomy (before 131I treatment) and 6 and 12 months after ablation therapy (Tg1, TgAb1 and Tg2, TgAb2, respectively). During one year of follow-up, in a total of 24 patients (21%) recurrent disease were confirmed by ultrasonography and whole-body-scanning, mostly. It was found significant correlation between serum Tg levels (measured preoperatively and postoperatively) and recurrent diseases (p < 0.05), while serum TgAb levels did not have any statistical significance. However, in multivariate regression analysis only Tg levels measured 12 months after the therapy (Tg2) remained a significant predictor of recurrent disease (p = 0.008). Although a high Tg level before surgery does not indicate that tumor is present, in the postoperative period and  after ablative therapy Tg has proven predictive value because stimulated Tg levels above 10 ng/ml confirmed that indicate residual or recurrent cancer, and its periodically measurements is recommended.




TÍTULO / TITLE:  - Two case reports of pilot percutaneous cryosurgery in familial multiple endocrine neoplasia type 1.

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

REVISTA / JOURNAL:  - Pancreas. 2013 Mar;42(2):353-7. doi: 10.1097/MPA.0b013e318258f233.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318258f233

AUTORES / AUTHORS:  - Li J; Zhang C; Chen J; Yao F; Zeng J; Huang L; Yang X; Liu W; Chen F; Xu K; Yang D; Niu L; Zuo J; Xu K; Liu D

INSTITUCIÓN / INSTITUTION:  - From the *National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; daggerGuangzhou Fuda Cancer Hospital, Guangzhou City, Guangdong Province, China; and double daggerGuangzhou Fuda Hospital, Guangzhou City, Guangdong Province, China.

RESUMEN / SUMMARY:  - ABSTRACT: We report 2 cases of familial multiple endocrine neoplasia type 1 syndrome (MEN 1) in related Malaysian Chinese individuals: the son had simultaneous primary lesions in the pancreatic tail, parathyroid, adrenal gland,  and hypophysis, with metastatic tumors in the left lung, mediastinum and spine; his mother had simultaneous primary lesions in the pancreatic head, parathyroid,  and hypophysis, with metastatic tumors in the liver, spine, ilium, chest wall, and rib. Genetic testing of the 2 patients showed the same mutation in exon 9 of  MEN1 (c.1288G>T, Glu430, encoding a stop codon). The tumors with the poorest prognosis and clinical sequelae were in the pancreas of both patients, and these  were treated by percutaneous cryoablation. The number of hypoglycemic episodes in the son improved for more than 120 days, and the abdominal space occupying lesion resolved in his mother.




TÍTULO / TITLE:  - Diffuse sclerosing variant of thyroid carcinoma presenting as Hashimoto thyroiditis: a case report.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:219-21.

AUTORES / AUTHORS:  - Vukasovic A; Kuna SK; Ostovic KT; Prgomet D; Banek T

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Dubrava University Hospital, Zagreb, Croatia. anamarijavukasovic@gmail.com

RESUMEN / SUMMARY:  - The aim of report is to present a case of a rare diffuse sclerosing variant of a  papillary thyroid carcinoma. A 15-year old girl referred for ultrasound examination because of painless thyroid swelling lasting 10 days before. An ultrasound of the neck showed diffusely changed thyroid parenchyma, without nodes, looking as lymphocytic thyroiditis Hashimoto at first, but with snow-storm appearance, predominantly in the right lobe. Positive thyroid peroxidase antibodies (TPO-AT) also suggested Hashimoto thyroiditis. Repeated US-FNAB (fine  needle-aspiration biopsy) of the right lobe revealed diffuse sclerosing variant of papillary thyroid carcinoma and patient underwent total thyreoidectomy. Patohistologic finding confirmed diffuse sclerosing variant of a papillary thyroid carcinoma in the both thyroid lobes and several metastatic lymph nodes. Two months later patient recived radioablative therapy with 3700 MBq (100 mCi) of 1-131 followed by levothyroxine replacement. At the moment, patient is without evidence of local or distant metastases and next regular control is scheduled in  6 months. In conclusion, a diffuse sclerosing variant is rare form of papillary thyroid carcinoma that echographically looks similar to Hashimoto thyroiditis and sometimes could be easily overlooked.




TÍTULO / TITLE:  - Lack of Prognostic Significance of Neuroendocrine Differentiation and Stem Cell Antigen Co-Expression in Resected Early-stage Non-small Cell Lung Cancer.

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Mar;33(3):981-90.

AUTORES / AUTHORS:  - Gottschling S; Jensen K; Herth FJ; Thomas M; Schnabel PA; Herpel E

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Oncology, Thorax Clinic/University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany. sandra.gottschling@thoraxklinik-heidelberg.de.

RESUMEN / SUMMARY:  - BACKGROUND: Neuroendocrine (NE) carcinomas of the lung exhibit expression of various stem cell antigens, and except for carcinoid tumours, carry a poor prognosis. Despite the fact that 10%-30% of all non-small cell lung carcinomas (NSCLC) which are not classified as NE carcinomas also show expression of NE markers, data on their prognostic significance are conflicting and analyses of the expression and relevance of stem cell antigens in this subgroup are lacking.  MATERIALS AND METHODS: Tissue specimens of 100 resected early-stage NSCLC were analyzed by immunohistochemistry for the expression and prognostic significance of NE markers. Moreover, the subgroup of NSCLC with NE differentiation (ND) were  assessed for the expression and prognostic significance of the stem cell antigens CD117, CD133 and breast cancer resistance protein-1 (ABCG2). RESULTS: ND correlated significantly with adenocarcinoma histology (p=0.035), but not with prognosis. In the subgroup of ND-NSCLC (n=80), the stem cell antigens CD117, CD133 and ABCG2 were expressed in 51%, 14% and 33% of the cases, but likewise, showed no association with prognosis or clinicopathological characteristics. CONCLUSION: This study indicates that neither ND, nor co-expression of the stem cell antigens CD117, CD133 or ABCG2, have a prognostic significance in resected early-stage NSCLC.




TÍTULO / TITLE:  - Hedgehog Signaling in Medullary Thyroid Carcinoma: A Novel Signaling Pathway.

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

REVISTA / JOURNAL:  - Thyroid. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1089/thy.2012.0474

AUTORES / AUTHORS:  - Bohinc B; Michelotti G; Diehl AM

INSTITUCIÓN / INSTITUTION:  - Duke University Hospital, Endocrinology, Diabetes, and Metabolism, 201 Trent Drive, Durham, North Carolina, United States, 27705, 440-376-9444, (919)-613-6984 ; brittany.bohinc@duke.edu.

RESUMEN / SUMMARY:  - Background: Locally or widely metastatic medullary thyroid carcinoma (MTC) is difficult to treat and therapeutic options are limited. Recently, kinase inhibitors have shown partial efficacy in this cancer, but there is a continued need for the development of novel therapeutics. Within this context, the Hedgehog (Hh) pathway has been implicated in several types of human tumors, and early clinical trials with Hh antagonists have validated Hh as a novel therapeutic target. For the first time, we evaluated Hh pathway activity in MTC and examined  the effect of Hh pathway perturbation in highly characterized MTC cell lines. Methods: We examined immunohistochemical expression of Hh signaling mediators Sonic Hedgehog (Shh) and Glioblastoma (Gli)2 in paraffin-embedded normal versus histologically characterized human MTC tissue. We examined pharmacologic disruption of Hh signaling in vitro using two established MTC cell lines (TT and  MZ-CRC-1). Hh signaling was either pharmacologically activated (SAG) or inhibited (GDC-0449) in MTC cell lines; Hh activity was assessed by qRT-PCR, Western blot analysis, and quantification of cellular growth and apoptotic activity. Results:  Our data showed increased expression of Hh signaling factors in human MTC compared to normal tissue. In vitro, activation of the Hh pathway resulted in increased expression of key Hh signaling components Smoothened (Smo) and Gli2. Conversely, inhibition of the Hh pathway decreased expression of these genes, leading to significantly reduced cellular growth and increased apoptosis. Conclusions: Hedgehog signaling components are markedly upregulated in MTC. Hh pathway inhibitors have potential as novel therapeutic options in patients with metastatic and/or surgically unresectable MTC.




TÍTULO / TITLE:  - A 45-year-old with neuroendocrine carcinoma of the prostate.

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

REVISTA / JOURNAL:  - Urology. 2013 Apr;81(4):714-6. doi: 10.1016/j.urology.2012.12.029. Epub 2013 Feb  13.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.urology.2012.12.029

AUTORES / AUTHORS:  - Reichard C; Gilligan T; Watts KE; Magi-Galluzzi C; Klein EA

INSTITUCIÓN / INSTITUTION:  - Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH. Electronic address: reichac@ccf.org.




TÍTULO / TITLE:  - Giant interaortocaval pheochromocytoma.

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

REVISTA / JOURNAL:  - Urology. 2013 Feb;81(2):e19-20. doi: 10.1016/j.urology.2012.10.034.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.urology.2012.10.034

AUTORES / AUTHORS:  - Kumar S; Kumar SD

INSTITUCIÓN / INSTITUTION:  - Department of Urology, Postgraduate Institute of Medical Education and Research,  Chandigarh, India. santoshsp1967jaimatadi@yahoo.co.in

RESUMEN / SUMMARY:  - Tumors arising from chromaffin cells, which are derived embryologically from neural crest cells, are known as pheochromocytomas or paragangliomas. These tumors in the retroperitoneum are usually located in close proximity to the aorta and inferior vena cava. Radical surgical resection is the treatment of choice for these tumors. We present a rare case of a postmenopausal woman who presented to us with a symptomatic giant retroperitoneal mass situated in the interaortocaval  region that we managed with surgical resection.




TÍTULO / TITLE:  - Bilateral pheochromocytomas, hemihyperplasia, and subtle somatic mosaicism: The importance of detecting low-level uniparental disomy.

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

REVISTA / JOURNAL:  - Am J Med Genet A. 2013 Mar 26. doi: 10.1002/ajmg.a.35831.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ajmg.a.35831

AUTORES / AUTHORS:  - Kalish JM; Conlin LK; Mostoufi-Moab S; Wilkens AB; Mulchandani S; Zelley K; Kowalski M; Bhatti TR; Russo P; Mattei P; Mackenzie WG; Livolsi V; Nichols KE; Biegel JA; Spinner NB; Deardorff MA

INSTITUCIÓN / INSTITUTION:  - Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania.

RESUMEN / SUMMARY:  - We report on a patient with early onset pediatric bilateral pheochromocytomas caused by mosaic chromosome 11p15 paternal uniparental isodisomy (UPD). Hemihyperplasia of the arm was diagnosed in a 4-month-old female and clinical methylation testing for 11p15 in the blood was normal, with a reported detection  threshold for mosaicism of 20%. She was subsequently diagnosed at 18 months with  bilateral pheochromocytomas. Single-nucleotide polymorphism (SNP) array analysis  of pheochromocytoma tissue demonstrated mosaic deletions of 8p12pter, 21q21.1qter, 22q11.23qter; commonly seen in pheochromocytomas. In addition, mosaic 11p15.3pter homozygosity was noted. Molecular testing for other causes of  pheochromocytomas was normal, suggesting that 11p15 homozygosity was the primary  event. Subsequent SNP array analysis of skin fibroblasts from the hyperplastic side demonstrated 5% mosaic paternal UPD for 11p15. We have subsequently used SNP array analysis to identify four patients with subtle hemihyperplasia with low-level mosaic UPD that was not detected by methylation analysis. Given the increased sensitivity of SNP array analysis to detect UPD along with the increased incidence of tumorigenesis in these UPD patients, we suggest that it has high utility in the clinical work-up of hemihyperplasia. The present case also suggests that 11p15 paternal UPD may be an under-detected mechanism of sporadic pheochromocytoma in the pediatric population. Furthermore, a review of the literature suggests that patients with 11p15 paternal UPD may present after 8 years of age with pheochromocytoma and raises the possibility that ultrasound screening could be considered beyond 8 years of age in this subset of hemihyperplasia and Beckwith-Wiedemann syndrome patients. © 2013 Wiley Periodicals, Inc.




TÍTULO / TITLE:  - Small cell neuroendocrine tumor of the larynx—a small case series.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:201-4.

AUTORES / AUTHORS:  - Mikic A; Zvrko E; Trivic A; Stefanovic D; Golubovic M

INSTITUCIÓN / INSTITUTION:  - Clinical Center of Serbia, Institute of Otorhinolaryngology and Maxillofacial Surgery, Belgrade, Serbia. braca5@eunet.rs

RESUMEN / SUMMARY:  - Neuroendocrine tumors are the most common nonsquamous types of laryngeal neoplasms. They are classified as typical carcinoids, atypical carcinoids, small-cell neuroendocrine carcinomas, and paragangliomas. The aim of the paper is to present four patients with small-cell neuroendocrine tumor arising in larynx.  There were one woman and three men whose ages were 47-77 years; all of them had metastases when first seen. The clinical presentation and management of such type of tumor are discussed. Small-cell neuroendocrine carcinomas are very aggressive  neoplasms. Patients could benefit from surgery, but radiotherapy and chemotherapy remain the treatment of choice. Examination of a large series is required to define the most useful diagnostic methods and the most successful treatment modalities.




TÍTULO / TITLE:  - Multiple endocrine neoplasia type 2A due to an exon 8 (G533C) mutation in a large North American kindred.

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

REVISTA / JOURNAL:  - Thyroid. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1089/thy.2012.0599

AUTORES / AUTHORS:  - Castro MR; Thomas BC; Richards M; Zhang J; Morris JC 3rd

INSTITUCIÓN / INSTITUTION:  - Mayo Clinic, Endocrinology, Metabolism & Nutrition, Rochester, Minnesota, United  States; castro.regina@mayo.edu.

RESUMEN / SUMMARY:  - Background: Medullary thyroid cancer, although most commonly sporadic, may be part of multiple endocrine neoplasia type 2 (MEN2) syndromes, generally due to mutations in the RET proto-oncogene. The majority of these mutations are located  in exons 10, 11, and 13-16. More rarely, mutations in other exons have been described. We report for the first time, a family from the United States with a rare mutation involving exon 8 of the RET proto-oncogene, corresponding to a Gly533Cys substitution (G533C) leading to the development of MEN2A syndrome in several affected family members. This mutation had only been previously described in a large family in Brazil and in 7.75% of patients with apparently sporadic medullary thyroid cancer (MTC) in Greece. Methods: Given strong index of suspicion, a genetic analysis to evaluate for uncommon mutations in the RET proto-oncogene identified the presence of the G533C missense mutation, despite initial negative screening for common mutations. We describe a family with a total of 47 individuals from 5 generations with multiple members affected with this mutation. Results: Our data suggest that in patients with this mutation, pheochromocytoma is more common than previously reported and that in some cases this mutation may be associated with a more aggressive phenotype than initially described. Conclusions: MEN2A due to the G533C mutation in Exon 8 may be more common and more aggressive than previously recognized. In patients with MTC with  negative screening for common mutations in RET oncogene, but a strong index of suspicion, DNA sequence analysis of less commonly involved exons should be considered.




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.




TÍTULO / TITLE:  - Merkel cell polyomavirus large T antigen is detected in rare cases of nonmelanoma skin cancer.

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

REVISTA / JOURNAL:  - J Cutan Pathol. 2013 Feb 26. doi: 10.1111/cup.12129.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cup.12129

AUTORES / AUTHORS:  - Mertz KD; Paasinen A; Arnold A; Baumann M; Offner F; Willi N; Cathomas G

INSTITUCIÓN / INSTITUTION:  - Institut fur Pathologie, Kantonsspital Baselland, Liestal, Switzerland.

RESUMEN / SUMMARY:  - BACKGROUND: Studies of Merkel cell polyomavirus (MCPyV) in nonmelanoma skin cancers (NMSC) other than Merkel cell carcinoma (MCC) produced controversial results. Therefore, we studied the prevalence of MCPyV in basal cell carcinoma (BCC) and in squamous cell carcinoma (SCC). METHODS: Tissue specimens were analyzed for the presence of MCPyV DNA by conventional polymerase chain reaction  (PCR). Expression of MCPyV large T protein was determined by immunohistochemistry. RESULTS: MCPyV DNA was frequently detected in skin cancers  by PCR, in 36 of 88 BCCs, in 21 of 75 SCCs and in 10 of 47 normal skin samples. In BCC, a significant difference in the detection rate compared to normal skin was observed. In contrast, weak reactivity for MCPyV large T antigen was detected only sporadically in immunosuppressed patients (2 of 88 BCCs, 1 of 75 SCCs). Mutations of the large T antigen of MCPyV were more frequently observed in MCC than in BCC/SCC. CONCLUSIONS: Our results suggest that the frequent detection of  the MCPyV genome in NMSC by PCR reflects ubiquitous spread of the virus. However, the low immunohistochemical detection rate of MCPyV and the lack of MCC-specific  MCPyV mutations argue against an essential role of MCPyV in the development of skin cancers other than MCC.




TÍTULO / TITLE:  - Pregnancy, Cesarean, and Pheochromocytoma: A Case Report and Literature Review.

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

REVISTA / JOURNAL:  - J Forensic Sci. 2013 Mar 25. doi: 10.1111/1556-4029.12107.

            ●● Enlace al texto completo (gratuito o de pago) 1111/1556-4029.12107

AUTORES / AUTHORS:  - Plu I; Sec I; Barres D; Lecomte D

INSTITUCIÓN / INSTITUTION:  - Institut medico-legal, 2 place Mazas, 75012, Paris, France.

RESUMEN / SUMMARY:  - A 43-year-old full-term pregnant woman (gravida 2, para 1, medical history of gestational diabetes mellitus) developed a sudden and malignant hypertension with hemoptysis, sweat, and tachycardia during a scheduled C-section. A dead newborn was delivered and was successfully resuscitated. The mother died after resistant  cardiac arrest. Autopsy and pathological analyses revealed an acute pulmonary edema and a necrotic and hemorrhagic voluminous tumor of the left adrenal gland,  which was a pheochromocytoma. Pheochromocytoma is a rare tumor of the adrenal glands which secretes catecholamines. In pregnant women, its symptoms can mimic gestational hypertension, preeclampsia or eclampsia, and gestational diabetes mellitus. The gestational diabetes mellitus was presumed to be a symptom of the pheochromocytoma, and cardiopulmonary failure the result from the necrosis of the tumor provoked by gravid uterus compression. From a medico-legal point of view, the tumor could not have been suspected during the pregnancy.




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.




TÍTULO / TITLE:  - Merkel cell carcinoma of the head and neck and associated second primary cancers: report of three cases.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:213-7.

AUTORES / AUTHORS:  - Snovak N; Bilic M; Zarkovic K

INSTITUCIÓN / INSTITUTION:  - Dr. Ivo Pedisic General Hospital, Department of Otorhinolaryngology and Oral Surgery, Sisak, Croatia. natalija.snovak@gmail.com

RESUMEN / SUMMARY:  - Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin carcinoma. The purpose of this study is to describe clinical and pathological characteristics, diagnostic procedure and treatment outcomes of the patients with MCC of the head and neck treated in Otorhinolaryngology, Head and Neck Surgery Department of the University Hospital Center Zagreb between the years 2007 and 2011. Three patients with MCC of the head and neck were treated during this period. First patient was diagnosed with MCC of the left retroauricular region with metastases in the lymph nodes of the left side of the neck, pT2N2M0 Stage IIIB. Second patient was diagnosed with anaplastic carcinoma of the lower lip, pT1N1bM0 Stage IIIB and third patient was diagnosed with MCC of the face which was previously treated as benign lesion, cT1N1bM0 Stage IIIB. Two of the patients had second primary tumor of different histology. All of the patients were treated with wide surgical excision of the tumor and neck dissection combined with adjuvant radiotherapy. Treatment outcome was poor and reason for this was late detection of disease. Menagment of the MCC patients requires multidisciplinary approach with high clinical suspicion of the treating specialist and pathologist  due to immunohistochemical techniques required for diagnosis. Detection of the MCC in earlier stages is necessary for the better survival rate.




TÍTULO / TITLE:  - Neurotransmitters and synaptic components in the Merkel cell-neurite complex, a gentle-touch receptor.

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

REVISTA / JOURNAL:  - Ann N Y Acad Sci. 2013 Apr;1279(1):13-21. doi: 10.1111/nyas.12057.

            ●● Enlace al texto completo (gratuito o de pago) 1111/nyas.12057

AUTORES / AUTHORS:  - Maksimovic S; Baba Y; Lumpkin EA

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology.

RESUMEN / SUMMARY:  - Merkel cells are an enigmatic group of rare cells found in the skin of vertebrates. Most make contacts with somatosensory afferents to form Merkel cell-neurite complexes, which are gentle-touch receptors that initiate slowly adapting type I responses. The function of Merkel cells within the complex remains debated despite decades of research. Numerous anatomical studies demonstrate that Merkel cells form synaptic-like contacts with sensory afferent terminals. Moreover, recent molecular analysis reveals that Merkel cells express  dozens of presynaptic molecules that are essential for synaptic vesicle release in neurons. Merkel cells also produce a host of neuroactive substances that can act as fast excitatory neurotransmitters or neuromodulators. Here, we review the  major neurotransmitters found in Merkel cells and discuss these findings in relation to the potential function of Merkel cells in touch reception.




TÍTULO / TITLE:  - Metastatic carcinoid tumors-are we making the cut?

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

REVISTA / JOURNAL:  - Am J Surg. 2013 Feb 13. pii: S0002-9610(13)00057-3. doi: 10.1016/j.amjsurg.2012.05.036.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.amjsurg.2012.05.036

AUTORES / AUTHORS:  - Coan KE; Gray RJ; Schlinkert RT; Pockaj BA; Wasif N

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Mayo Clinic, 5777 E Mayo Boulevard, Phoenix, AZ 85054, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Although controversial, surgical resection for metastatic carcinoid tumors (MCTs) can potentially prolong survival. METHODS: Patients with MCTs were  identified from the Surveillance, Epidemiology and End Results database. Patients undergoing surgery were compared to unresected patients. RESULTS: Surgery was performed in 33% of patients. Predictors of surgery included age <50 years (odds  ratio [OR], 2.4), low grade (OR, 3.1), and the appendix (OR, 36.2) or small intestine (OR, 27.2) as the primary site. Predictors of adverse survival included high grade (hazard ratio, 2.4) and no surgery (hazard ratio, 2.5) or surgery on only primary or distant disease (hazard ratio, 1.5) compared with surgery for both. Survival at 5 years was 5% with no surgery, 28% with surgery on either site, and 46% with surgery at both sites (P < .001). CONCLUSIONS: Surgery for MCTs is more common in younger patients, those with low-grade disease, and those  with small bowel or appendiceal primary tumors. Although selection bias cannot be excluded, these data lend support to “debulking” for MCT.




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.




TÍTULO / TITLE:  - Hypocalcaemia after thyroid surgery for differentiated thyroid carcinoma: preliminary study report.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:73-8.

AUTORES / AUTHORS:  - Radivojevic RC; Prgomet D; Markesic J; Ezgeta C

INSTITUCIÓN / INSTITUTION:  - University of Zagreb, Zagreb University Hospital Centre, Department of Anesthesiology and Intensive Care Unit, Zagreb, Croatia. renata.curic@gmail.com

RESUMEN / SUMMARY:  - Hypocalcaemia is one of the most common major complications after thyroid surgery with the wide range of incidence from 6.9 to 46%. Thyroidectomy is usually first  choice treatment for differentiated thyroid carcinoma (DTC). The study comprised  46 adult patients operated at Zagreb University Hospital Centre. Intraoperative and postoperative ionized calcium and intact parathyroid hormone (iPTH) were studied. The object of this study is to investigate risk factors, incidence of hypocalcaemia after surgical treatment of differentiated thyroid carcinoma, and the role of iPTH in comparison to ionized calcium as a predictor for hypocalcaemia.




TÍTULO / TITLE:  - Synchronous occurrence of paraganglioma of the glomus jugulare and olfactory groove meningioma.

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

REVISTA / JOURNAL:  - Clin Neuropathol. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300606

AUTORES / AUTHORS:  - Mittal S; Monsell EM; Narayanan S; Kupsky WJ; Guthikonda M; Mittal S




TÍTULO / TITLE:  - A rare association of pulmonary carcinoid, lymphoma, and sjogren syndrome.

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

REVISTA / JOURNAL:  - Ann Thorac Surg. 2013 Mar;95(3):1086-7. doi: 10.1016/j.athoracsur.2012.06.051.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.06.051

AUTORES / AUTHORS:  - Taylor WS; Vaughan P; Trotter S; Rajesh PB

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Heartlands Hospital, Birmingham, United Kingdom.  wstjtaylor@doctors.org.uk

RESUMEN / SUMMARY:  - Pulmonary carcinoid and pulmonary lymphoma are both rare cancers and are seldom seen together. Cases have been reported of their coexistence in the gastrointestinal tract, but our literature searches only found a single case of their coexistence in the lung. We discuss our case as well as the literature to try to find a connection and explanation for this occurrence.




TÍTULO / TITLE:  - Multiple endocrine neoplasia type 1 with upper gastrointestinal hemorrhage and perforation: A case report and review.

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

REVISTA / JOURNAL:  - World J Gastroenterol. 2013 Feb 28;19(8):1322-6. doi: 10.3748/wjg.v19.i8.1322.

            ●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i8.1322

AUTORES / AUTHORS:  - Lu YY; Zhu F; Jing DD; Wu XN; Lu LG; Zhou GQ; Wang XP

INSTITUCIÓN / INSTITUTION:  - Ying-Ying Lu, Feng Zhu, Da-Dao Jing, Xie-Ning Wu, Lun-Gen Lu, Xing-Peng Wang, Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

RESUMEN / SUMMARY:  - Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary syndrome known to predispose subjects to endocrine neoplasms in a variety of tissues such as the parathyroid glands, pituitary gland, pancreas and gastrointestinal tract. We herein report a patient with a past history of pituitary adenoma, presenting with symptoms of chronic diarrhea for nearly one year and a sudden upper gastrointestinal hemorrhage as well as perforation without signs. Nodules in the  duodenum and in the uncinate process and tail of pancreas and enlargement of the  parathyroid glands were detected on preoperative imaging. Gastroscopy revealed significant ulceration and esophageal reflux diseases. The patient underwent subtotal parathyroidectomy and autotransplantation, pylorus-preserving pancreaticoduodenectomy and pancreatic tail resection and recovered well. The results observed in our patient suggest that perforation and bleeding of intestine might be symptoms of Zollinger-Ellison Syndrome in patients with MEN1.




TÍTULO / TITLE:  - Notch1-Hes1 signalling axis in the tumourigenesis of biliary neuroendocrine tumours.

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

REVISTA / JOURNAL:  - J Clin Pathol. 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1136/jclinpath-2012-201273

AUTORES / AUTHORS:  - Harada K; Sato Y; Ikeda H; Hsu M; Igarashi S; Nakanuma Y

INSTITUCIÓN / INSTITUTION:  - Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan.

RESUMEN / SUMMARY:  - AIMS: Biliary neuroendocrine tumours (NETs) are rare and mostly exist as a component of mixed adenoneuroendocrine carcinomas (MANECs). Although the NET component in biliary MANECs is generally more malignant and clinically more important to the prognosis than the ordinary adenocarcinomatous component, the histogenesis of biliary NET has not been clarified. In this study, the role of the Notch1-Hes1 signalling axis in the histogenesis of biliary NETs was examined. METHODS: Immunohistochemistry for Notch1, its ligand Jagged1 and Hes1 was performed using surgical specimens from 11 patients with biliary MANEC. Moreover, after the knock-down of Notch1 mRNA expression in a cholangiocarcinoma cell line, the expression of chromogranin A (a neuroendocrine marker) and Ascl1 (a neuroendocrine-inducing molecule inhibited by activated Hes1) was examined by quantitative PCR. RESULTS: Histological examination revealed that the adenocarcinomatous components were predominately located at the luminal surface of the MANEC and the majority of stromal invasion involved NET components. Ordinary adenocarcinomas and non-neoplastic biliary epithelium constantly expressed Notch1, Jagged1 and Hes1, but the expression of Notch1 and Hes1 was decreased or absent in NET components, suggesting interference with the Notch1-Hes1 signalling axis in biliary NET. Moreover, in the cholangiocarcinoma cell line in which the expression of Notch1 mRNA was knocked down, the mRNA expression of Ascl1 and chromogranin A was increased. CONCLUSIONS: The Notch1-Hes1 signalling axis suppresses neuroendocrine differentiation and maintains tubular/acinar features in adenocarcinoma and non-neoplastic epithelium in the biliary tree. Moreover, a disruption of this signalling axis may be associated with the tumourigenesis of NETs in biliary MANEC.




TÍTULO / TITLE:  - Intramuscular corpora amylacea adjacent to ileal low-grade neuroendocrine tumours (typical carcinoids): a light microscopic, immunohistochemical and ultrastructural study.

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

REVISTA / JOURNAL:  - J Clin Pathol. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1136/jclinpath-2012-201415

AUTORES / AUTHORS:  - Hechtman JF; Gordon RE; Harpaz N

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Mount Sinai School of Medicine, New York, New York, USA.

RESUMEN / SUMMARY:  - AIMS: The purposes of this study are to (1) document the prevalence of intracytoplasmic inclusions adjacent to ileal well-differentiated neuroendocrine  tumours (WNETs), (2) examine whether and how tumour and patient characteristics are associated with inclusions and (3) investigate their properties on special stains and electron microscopy in comparison with corpora amylacea (CA). METHODS: We examined the resection slides from 26 ileal, 5 gastric and 5 rectal cases of WNET. Inclusions were readily identified with H&E staining. Histochemical, immunohistochemical and ultrastructural evaluations were performed on the block with the highest number of inclusions. RESULTS: Intracytoplasmic inclusions occurred adjacent (<1 mm) to 15 of 26 (57.7%) ileal WNETs. Patients with and without inclusions were of similar mean ages (59.5 vs 57.4 years; p=0.88), but NETs with inclusions were larger than those without inclusions (3.3 vs 1.7 cm, p=0.03). Inclusions were neither associated with gastric (mean age=65 years, mean diameter=1.5 cm) or rectal WNETs (mean age=47.8 years, mean diameter=0.5 cm) (p=0.01), nor were they present >1 mm from ileal NETs. CA stained strongly for ubiquitin, DPAS and Alcian blue; faintly and peripherally for desmin and smooth muscle actin and negatively for calcium. Ultrastructurally, their appearance was  consistent with filaments, some with cores of particle matter. CONCLUSIONS: Our results suggest that these inclusions are virtually identical to CA and present adjacent to the majority of ileal WNET. They may be the result of a degenerative  process, possibly due to chronic myocyte stress from an infiltrating slow growing tumour mass or local hormonal effects.




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


INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine.




TÍTULO / TITLE:  - Pathology reporting of neuroendocrine tumors: essential elements for accurate diagnosis, classification, and staging.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):23-36. doi: 10.1053/j.seminoncol.2012.11.001.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.001


INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. klimstrd@mskcc.org

RESUMEN / SUMMARY:  - Much recent debate has focused on the optimal classification of epithelial neuroendocrine tumors (NETs). Multiple different systems of terminology, grading, and staging have been proposed, and some systems combine elements of grade and stage into a single prognostic classification. Recently, national and international consensus groups have attempted to standardize the classification of NETs, especially for those arising in the gastrointestinal tract and pancreas. Furthermore, the recognition that common classification criteria (such as proliferative rate) span multiple different systems allows the basic data necessary to predict outcome and tailor therapy to be included in pathology reports, even though a single uniform system of terminology may remain elusive. Formal tumor-node-metastasis (TNM)-based staging systems also have been developed recently, and advances in the treatment of some NETs (pancreatic in particular) are pointing towards the need to assess therapeutic biomarkers in routine practice. This review will present the most widely used systems for classifying,  grading, and staging NETs and will summarize the recommendations for the data to  be included in standard pathology reports of these uncommon tumors.




TÍTULO / TITLE:  - Mixed adenoneuroendocrine carcinoma (MANEC) of the esophagogastric junction predominantly consisting of poorly differentiated neuroendocrine carcinoma.

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

REVISTA / JOURNAL:  - Endoscopy. 2013;45 Suppl 2 UCTN:E16-7. doi: 10.1055/s-0032-1326113. Epub 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1326113

AUTORES / AUTHORS:  - Veits L; Lang-Schwarz C; Volkholz H; Falkeis C; Vieth M; Schulz H

INSTITUCIÓN / INSTITUTION:  - Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany. lothar.veits@klinikum-bayreuth.de




TÍTULO / TITLE:  - A Unique Retrorectal Tumor With Neuroendocrine Differentiation: Case Report and Review of the Literature.

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

REVISTA / JOURNAL:  - Int J Surg Pathol. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1066896913476738

AUTORES / AUTHORS:  - Misawa S; Horie H; Yamaguchi T; Kobayashi S; Kumano H; Lefor AT; Yasuda Y

RESUMEN / SUMMARY:  - Retrorectal or presacral tumors are very rare. We report a unique case of a retrorectal tumor with neuroendocrine differentiation, consisting of high- and low-grade components. A 53-year-old woman treated for a perianal abscess at another clinic was referred to our hospital for continued anal pain. Digital rectal examination identified a soft tumor with a smooth surface in the lower rectum. Pelvic computed tomography and magnetic resonance imaging detected a large cystic tumor measuring 8 cm in diameter in the retrorectal space of the pelvis. The border between the tumor and rectal wall, levator ani and vaginal wall was obscure. Fine-needle aspiration cytology was highly suggestive of carcinoma. Abdominoperineal resection was performed, and the tumor was histologically diagnosed as a neuroendocrine carcinoma based on immunohistochemical staining. No previous case has been reported with cystic growth of a neuroendocrine carcinoma in the retrorectal space.




TÍTULO / TITLE:  - Imaging of neuroendocrine tumors.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):109-19. doi: 10.1053/j.seminoncol.2012.11.008.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.008

AUTORES / AUTHORS:  - Leung D; Schwartz L

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Columbia University, New York, NY 10032, USA.

RESUMEN / SUMMARY:  - Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that differ in their biological, chemical, and physical behaviors depending on the degree of  differentiation and locations. Consequently, evaluation of these tumors is complex, requiring clinical history, physical examination, laboratory data, and imaging. With advances in morphologic and functional imaging techniques, we now have tools for caring of patients with these tumors at diagnosis, staging, treatment assessment, and prognosis prediction. In general, no single imaging modality can provide all the necessary information. However, well-chosen combinations of available imaging modalities based on the indications, strength and limitations of the modalities, and local expertise will provide optimal evaluation of patients with NETs.




TÍTULO / TITLE:  - Carcinoid of the Ovary: Diagnostic Challenge on Fine-Needle Aspiration Cytology.

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

REVISTA / JOURNAL:  - Diagn Cytopathol. 2013 Mar 1. doi: 10.1002/dc.22960.

            ●● Enlace al texto completo (gratuito o de pago) 1002/dc.22960

AUTORES / AUTHORS:  - Kumar M; Rajwanshi A; Dey P

INSTITUCIÓN / INSTITUTION:  - Department of Cytology, Post Graduate Institute of Medical Eduaction and Research, Chandigarh, India.

RESUMEN / SUMMARY:  - Carcinoid of the ovary is an uncommon tumor. In the present article we have described the cytological features of carcinoid of the ovary in a 53-year old post-menopausal female. The patient presented with abdominal discomfort and loose stools. Ultrasound-guided fine-needle aspiration cytology (FNAC) of the left adnexal mass showed clusters and also scattered, relatively monomorphic population of tumor cells with vague rosette-like structures. Cytological diagnosis of malignant ovarian tumor possibly sex cord stromal tumor or carcinoid of ovary was offered and subsequent histopathology and immunohistochemistry confirmed the diagnosis of carcinoid. Diagn. Cytopathol. 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.




TÍTULO / TITLE:  - Malignant and Benign Sinonasal Paragangliomas.

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

REVISTA / JOURNAL:  - Laryngoscope. 2013 Jan 31. doi: 10.1002/lary.23985.

            ●● Enlace al texto completo (gratuito o de pago) 1002/lary.23985

AUTORES / AUTHORS:  - Papaspyrou K; Welkoborsky HJ; Gouveris H; Mann WJ

INSTITUCIÓN / INSTITUTION:  - Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz.

RESUMEN / SUMMARY:  - OBJECTIVES/HYPOTHESIS: To report on the clinical course and management of sinonasal paragangliomas (PGLs). STUDY DESIGN AND METHODS: Retrospective chart review of six patients with PGLs of the nasal cavity and paranasal sinuses. RESULTS: Three patients had tumors with malignant clinical behavior with cerebral metastases or infiltration of brain and local recurrence, despite surgery and/or  radiotherapy, while three patients demonstrated a benign course. CONCLUSION: Sinonasal paragangliomas are frequently malignant. If malignant, they are very aggressive, with rapid local spread as well as high metastatic potential despite  surgical resection; and they have a poor prognosis. Malignancy cannot be diagnosed on histology, but only on the basis of clinical behavior. Intracranial  metastasis is commonly expected. Long-term follow-up, with particular emphasis put on the intracranial structures, is mandatory as recurrences or metastasis may occur even after a long time interval. LEVEL OF EVIDENCE: 4. Laryngoscope, 2012.




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.




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.




TÍTULO / TITLE:  - Pheochromocytoma and markers of oxidative stress.

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

REVISTA / JOURNAL:  - Physiol Res. 2013 Mar 14.

AUTORES / AUTHORS:  - Turkova H; Petrak O; Skrha J; Widimsky J Jr; Zelinka T

INSTITUCIÓN / INSTITUTION:  - Third Medical Department of the First Faculty of Medicine and General University  Hospital, Prague, Czech Republic. tzeli@lf1.cuni.cz.

RESUMEN / SUMMARY:  - High levels of catecholamines in pheochromocytoma (PHEO) are associated with risk of cardiovascular complications. In this study, we looked for potential differences in markers of oxidative stress - vitamin C, superoxide dismutase (SOD) and malondialdehyde (MDA) in PHEO before and after the operation. We studied 18 subjects with PHEO who were examined before and approximately one year after the successful tumor removal (free of disease). All subjects had elevated urinary epinephrine and/or norepinephrine levels before the operation. Vitamin C  levels increased significantly after the operation from 61+/-27 to 77+/-20 micromol/l (P=0.02), and MDA decreased significantly after the tumor removal from 2.6+/-0.4 to 2.0+/-0.6 micromol/l (P=0.01). However, no changes were found in SOD activity before and after the operation. In conclusion, increased catecholamine production in PHEO is accompanied by decreased levels of vitamin C and increased  levels of MDA which may indicate the activation of oxidative stress in PHEO. Successful operation was associated with lowering of oxidative stress by using both biomarkers. On the contrary, no changes in SOD activity before and after the tumor removal were noted.




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.




TÍTULO / TITLE:  - Can C-Arm Cone-Beam CT Detect a Micro-Embolic Effect After TheraSphere Radioembolization of Neuroendocrine and Carcinoid Liver Metastasis?

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

REVISTA / JOURNAL:  - Cancer Biother Radiopharm. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1390

AUTORES / AUTHORS:  - Pellerin O; Lin M; Bhagat N; Shao W; Geschwind JF

INSTITUCIÓN / INSTITUTION:  - 1 Division of Vascular and Interventional Radiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital , Baltimore, Maryland.

RESUMEN / SUMMARY:  - Abstract Rational and Objective: Radioembolization with yttrium-90 microspheres is a therapy that is used for hepatic tumors. 20-30 mum microspheres loaded with  Y90 are supposedly occluding tumor vessels at the capillary level. Then, these spheres deliver high-dose radiation to the tumor. However, this theoretical embolic effect has never been appreciated in imaging. Dual-Phase cone-beam computed tomography (DPCBCT) is a multi-phasic intra-procedural scan that uses only one contrast media injection to visualize early (feeding vessel) and delayed (capillary level) tumor enhancement. The purpose of this study was to determine whether there is a micro-embolic effect induced by TheraSpheres® (MDS Nordion,  Ottawa, Ontario, Canada) at the capillary level by using DPCBCT imaging. Material and Methods: 14 patients with 72 carcinoid or neuroendocrine tumors were treated  with radioembolization, and all underwent DPCBCT (Allura Xper, Philips Healthcare) imaging before and immediately after radioembolization with TheraSpheres®. Tumor enhancement was measured in each phase by drawing a region of interest within the tumors. Results: 72 tumors were evaluated: average tumor density in the early arterial phase was 241 and 230 Hounsfield units (HU) (p<0.001) before and after radioembolization, respectively; the average density in the delayed arterial phase was 226 and 161 HU (p<0.001) before and after radioembolization, respectively. Average difference in tumor attenuation before and after radioembolization in early arterial and delayed phase was 11 HU and 64  HU (p<0.001), respectively. Conclusion: The significant decrease in tumor enhancement in the DPCBCT delayed phase after TheraSpheres® injection indicates that there is an appreciable microembolic effect at the tumor capillary bed level.




TÍTULO / TITLE:  - Laparoscopic resection of adrenal and extra-adrenal pheochromocytoma.

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

REVISTA / JOURNAL:  - J Endourol. 2013 Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 1089/end.2012.0745


INSTITUCIÓN / INSTITUTION:  - Faculty of Medicine, National University Corporation, University of Toyama, Department of Urology, 2630 Sugitani, Toyama, Japan, 930-0194, +81-76-434-2281; nozaki0921@yahoo.co.jp.

RESUMEN / SUMMARY:  - OBJECTIVES: Laparoscopic resection of extra-adrenal pheochromocytoma (EAPs) requires meticulous surgical procedures because of changes in anatomical disposition and/or proximity to major blood vessels. Complete resection can be traumatic and may cause an increase in catecholamine levels. We present our experiences with laparoscopic resection of EAP (LEAP) and compare the intraoperative hemodynamics with those during laparoscopic resection of adrenal pheochromocytoma (LAP). METHODS: We retrospectively reviewed the medical records  of 5 patients who underwent LEAP (retrocaval EAP, n = 2; interaortocaval EAP, n = 1; periadrenal EAP, n = 2) and 5 who underwent LAP between October 2001 and October 2011. We also evaluated fluctuations in blood pressure (BP) reported during both surgeries. RESULTS: The tumors were successfully resected under laparoscopic guidance in both groups, and conversion to open surgery or blood transfusion was not required. Intraoperative hypertension (BP >200 mmHg) was observed in 3 LEAP and 4 LAP patients, whereas intraoperative hypotension (BP <80 mmHg) was observed in 5 LEAP and 3 LAP patients. However, no significant differences were observed between groups. CONCLUSIONS: Laparoscopy is the method  of choice for surgeons experienced in EAP resection because it is feasible and reproducible with appropriate preoperative planning, similar to LAP.




TÍTULO / TITLE:  - Carotid body paragangliomas: a systematic study on management with surgery and radiotherapy.

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

REVISTA / JOURNAL:  - Eur Arch Otorhinolaryngol. 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00405-013-2384-5

AUTORES / AUTHORS:  - Suarez C; Rodrigo JP; Mendenhall WM; Hamoir M; Silver CE; Gregoire V; Strojan P; Neumann HP; Obholzer R; Offergeld C; Langendijk JA; Rinaldo A; Ferlito A

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology, Hospital Universitario Central de Asturias Oviedo,  Oviedo, España.

RESUMEN / SUMMARY:  - The definitive universally accepted treatment for carotid body tumors (CBT) is surgery. The impact of surgery on cranial nerves and the carotid artery has often been underestimated. Alternatively, a few CBTs have been followed without treatment or irradiation. The goal of this study is to summarize the existing evidence concerning the efficacy and safety of surgery and external beam radiotherapy (EBRT) for CBT. Relevant articles were identified using strict criteria for systematic searches. Sixty-seven articles met the criteria which included 2,175 surgically treated patients. On the other hand, 17 articles including 127 patients treated with EBRT were found. Long-term control of the disease was obtained in 93.8 % of patients who received surgical treatment and in 94.5 % of the radiotherapy group. Surgery resulted in 483 (483/2,175 = 22.2 %) new cranial nerve permanent deficits, whereas in the EBRT group, no new deficits  were recorded (p = 0.004). The common/internal carotid artery was resected in 271 (12.5 %) patients because of injury or tumor encasement, with immediate reconstruction in 212 (9.7 %) patients. Three percent (60) of patients developed  a permanent stroke and 1.3 % (26) died due to postoperative complications. The major complications rates and the mortality after completion of the treatment also were significantly higher in surgical series compared to EBRT series. This systematic analysis highlights evidence that EBRT offers a similar chance of tumor control with lower risk of morbidity as compared to surgery in patients with CBT. This questions the traditional notion that surgery should be the mainstay of treatment.




TÍTULO / TITLE:  - Giant neuroendocrine tumour localized to the thoracoabdomen.

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

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2013 Mar 3.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezt113

AUTORES / AUTHORS:  - Pikin O; Sidorov D; Amiraliev A; Kirsanova O

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, P.A. Hertzen Moscow Oncology Research Institute,  Moscow, Russia.




TÍTULO / TITLE:  - Can Hybrid SPECT-CT Overcome the Limitations Associated With Poor Imaging Properties of 131I-MIBG?: Comparison With Planar Scintigraphy and SPECT in Pheochromocytoma.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318279bcb2

AUTORES / AUTHORS:  - Sharma P; Dhull VS; Jeph S; Reddy RM; Singh H; Naswa N; Bal C; Kumar R

INSTITUCIÓN / INSTITUTION:  - From the Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

RESUMEN / SUMMARY:  - OBJECTIVE: This study aimed to evaluate the incremental value of I-MIBG hybrid SPECT-CT over planar scintigraphy (PS) and SPECT alone in patients with clinical  or biochemical suspicion of pheochromocytoma. METHODS: A total of 126 adrenals of 63 patients (mean [SD] age, 28.6 [15.7] years; male patients, n = 34; female patients, n = 29) with clinical or biochemical suspicion of pheochromocytoma were retrospectively evaluated. All patients had undergone I-MIBG SPECT-CT of adrenal  region. The PS, SPECT, and SPECT-CT images were independently evaluated by 2 nuclear medicine physicians with 6 years (R1) and 2 years (R2) experience and in  separate sessions 1 week apart. A scoring scale of 1 to 5 was used, in which 1 is definitely abnormal, 2 is probably abnormal, 3 is indeterminate, 4 is probably normal, and 5 is definitely normal. Sensitivity, specificity, predictive values were calculated taking a score 2 or less as abnormal. With receiver operating characteristic (ROC) curve analysis, areas under the curve (AUC) were calculated  for each modality and compared. Histopathology and/or clinical/imaging follow-up  were taken as reference standard. RESULTS: Of the 126 adrenals evaluated, 29 were indeterminate on PS for R1 and 48 for R2, 39 were indeterminate on SPECT for both, and on SPECT-CT, 1 was indeterminate for R1 and 2 for R2. SPECT-CT correctly characterized 28 of 29 indeterminate adrenals on PS and 37 of 39 indeterminate adrenals on SPECT for R1. Similarly, for R2, SPECT-CT correctly characterized 45 of 48 indeterminate adrenals on PS and 33 of 39 indeterminate adrenals on SPECT. On ROC comparison, PS was inferior to SPECT (P = 0.040 for R1; P < 0.001 for R2) and SPECT-CT (P = 0.001 for R1; P < 0.001 for R2) for both the  observers. Moreover, SPECT was inferior to SPECT-CT for both the observers (P = 0.017 for R1 and P = 0.001 for R2). Accuracy of SPECT-CT (R1, 97.6%; R2, 97.6%) was higher than PS (R1, 91.2%; R2, 84.1%) and SPECT (R1, 94.4%; R2, 86.5%). Interobserver agreement was highest for SPECT-CT (kappa = 0.966) as compared with PS (kappa = 0.815) and SPECT (kappa = 0.826). CONCLUSIONS: I-MIBG hybrid SPECT-CT shows high sensitivity and specificity for characterizing adrenal lesions in patients with clinical or biochemical suspicion of pheochromocytoma and is superior to PS and SPECT alone. It will be especially useful in countries where I-MIBG is not available.




TÍTULO / TITLE:  - Comparison of 18F-FDG PET/CT and 68Ga-DOTATATE PET/CT Imaging in Metastasized Merkel Cell Carcinoma.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Apr;38(4):283-4. doi: 10.1097/RLU.0b013e318281658e.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318281658e

AUTORES / AUTHORS:  - Epstude M; Tornquist K; Riklin C; di Lenardo F; Winterhalder R; Hug U; Strobel K

INSTITUCIÓN / INSTITUTION:  - From the *Departments of Nuclear Medicine and Radiology, daggerOncology, double daggerRadiation Oncology, and section signHand and Plastic Surgery, Cantonal Hospital Lucerne, Lucerne, Switzerland.

RESUMEN / SUMMARY:  - Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine tumor of the skin in elderly patients with higher mortality compared with melanoma. No evidence-based standardized chemotherapy exists for metastasized patients.We report the case of an 87-year-old patient with the history of resection of a large MCC of the parietal scalp planned for radiotherapy and staged with FDG PET/CT showing disseminated distant metastases. Ga-DOTATATE PET/CT revealed more  extensive tumor load compared with FDG, and due to the intensive expression of somatostatin receptors the patient qualified for Y DOTATOC therapy.




TÍTULO / TITLE:  - Non-functional parathyroid gland carcinoma, a rare malignant tumor of the head and neck.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:23-5.

AUTORES / AUTHORS:  - Kotromanovic Z; Birtic D; Vceva A; Medic D; Zubcic Z; Mihalj H; Kotromanovic Z; Eric S; Dmitrovic B; Stefanic M

INSTITUCIÓN / INSTITUTION:  - “J. J. Strossmayer” University, Osijek University Hospital Centre, Department of  Otorhinolaryngology Head and Neck Surgery, Osijek, Croatia.

RESUMEN / SUMMARY:  - Carcinoma of the parathyroid gland is a very rare tumor of the head and neck. The largest number of carcinomas are discovered by chance. (intraoperatively, during  surgery removal of the parathyroid gland are adenomas). Around 1% of the primary  parathyreoidism is caused by the cancer of parathyroid glands. Only 10% of these  rare tumors make up dysfunctional cancer of parathyroid glands. There have been 24 cases reported of this disease in the literature. The focus of our study is to present a case of this disease and to review the published literature to date.




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.




TÍTULO / TITLE:  - Carcinoid tumors of the small-bowel: Evaluation with 64-section CT-enteroclysis.

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

REVISTA / JOURNAL:  - Eur J Radiol. 2013 Mar 4. pii: S0720-048X(13)00083-1. doi: 10.1016/j.ejrad.2013.02.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2013.02.013

AUTORES / AUTHORS:  - Soyer P; Dohan A; Eveno C; Dray X; Hamzi L; Hoeffel C; Kaci R; Boudiaf M

INSTITUCIÓN / INSTITUTION:  - Department of Body and Interventional Imaging, Hopital Lariboisiere - AP-HP, 2 rue Ambroise Pare, 75475 Paris Cedex 10, France; Universite Paris-Diderot, Sorbonne-Paris Cite, 10 rue de Verdun, 75010 Paris, France; UMR INSERM 965, Hopital Lariboisiere, 2 rue Amboise Pare, 75010 Paris, France. Electronic address: philippe.soyer@lrb.aphp.fr.

RESUMEN / SUMMARY:  - PURPOSE: To describe the imaging presentation of carcinoid tumors of the small-bowel at 64-section CT-enteroclysis and determine the sensitivity of this technique for tumor detection. PATIENTS AND METHODS: The 64-section CT-enteroclysis examinations of 22 patients with histopathologically proven small-bowel carcinoid tumors and those of 6 patients with suspected recurrence after small-bowel resection for carcinoid tumor were reviewed. Images were analyzed with respect to imaging presentation. Sensitivity, specificity, and accuracy, of 64-section CT-enteroclysis for the diagnosis of carcinoid tumor of the small-bowel were estimated with 95% confidence intervals (CIs). RESULTS: Twenty-five carcinoid tumors were confirmed in 22 patients (prevalence, 22/28; 79%). Overall sensitivity for carcinoid tumor detection was 76% (19/25; 95%CI: 55-91%) on a per-lesion basis. On a per-patient basis, 64-section CT-enteroclysis had a sensitivity of 86% (19/22; 95%CI: 65-97%), a specificity of 100% (6/6; 95%CI: 54-100%) and an accuracy of 89% (25/28; 95%CI: 72-98%) for the diagnosis of carcinoid tumor. Focal small-bowel wall thickening, mesenteric stranding, and  mesenteric mass were found in 20/22 (91%), 18/22 (82%) and 15/22 (68%) patients with pathologically confirmed tumors. CONCLUSION: 64-Section CT-enteroclysis shows highly suggestive features for the diagnosis of carcinoid tumor of the small-bowel and achieves high degrees of sensitivity for tumor detection.




TÍTULO / TITLE:  - Management of an incidentally discovered hypoglossal paraganglioma.

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

REVISTA / JOURNAL:  - Am Surg. 2013 Mar;79(3):114-5.

AUTORES / AUTHORS:  - Harmon L; Viney S; Frazee R; Van Husen R

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Texas Tech University Health Sciences, Center-Permian Basin, Odessa, Texas, USA.




TÍTULO / TITLE:  - The management of extrapulmonary poorly differentiated (high-grade) neuroendocrine carcinomas.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):100-8. doi: 10.1053/j.seminoncol.2012.11.011.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.011

AUTORES / AUTHORS:  - Smith J; Reidy-Lagunes D

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Division of Colorectal Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

RESUMEN / SUMMARY:  - Extrapulmonary high-grade neuroendocrine carcinomas (HGNECs) are rare but aggressive tumors that can be found throughout the body but are most commonly located in the gastrointestinal (GI) and the genitourinary tracts. They also have been described in the thymus, breast, oropharynx, and other organs. Due to the rarity of these tumors, publications are limited to small series and, as a result, treatment regimens are extrapolated from more robust data published on pulmonary HGNECs. For metastatic disease, platinum-based chemotherapy is the backbone of treatment. For localized disease, there are currently no standard treatment algorithms. Surgical resection with low morbidity is a reasonable treatment option, particularly in lesions where the possibility of obstruction is high. However, given the very high risk of disease recurrence, a multimodality approach with either neoadjuvant or adjuvant therapy is warranted. For locally advanced disease, chemoradiation should be considered, incorporating a platinum-based regimen when possible. Chemoradiation also should be considered when primary resection would lead to significant morbidity, such as with rectal,  pancreas, and esophageal HGNECs.




TÍTULO / TITLE:  - Update on the management of unusual neuroendocrine tumors: pheochromocytoma and paraganglioma, medullary thyroid cancer and adrenocortical carcinoma.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):120-33. doi: 10.1053/j.seminoncol.2012.11.009.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.009

AUTORES / AUTHORS:  - Strosberg JR

INSTITUCIÓN / INSTITUTION:  - Gastrointestinal and Neuroendocrine Tumor Division, H. Lee Moffitt Cancer Center  and Research Institute, Tampa, FL 33612, USA. jonathan.strosberg@moffitt.org

RESUMEN / SUMMARY:  - Pheochromocytomas, paragangliomas, and medullary thyroid carcinomas (MTCs) originate in cells that share a common neuroectodermal origin. Like other neuroendocrine neoplasms, they are characterized by a propensity to secrete amines (epinephrine and norepinephrine) and peptide hormones (calcitonin). Improved understanding of underlying molecular pathways, such as mutations of the RET (rearranged during transfection) proto-oncogene, has led to new rational targeted therapies. Adrenocortical carcinomas (ACCs) originate in the steroid hormone-producing adrenal cortex. While tumors of the adrenal cortex are not, strictly speaking, part the “diffuse neuroendocrine system,” they are often included in neuroendocrine tumor guidelines due to their orphan status. In this update on management of unusual neuroendocrine tumors, we review the biology and  treatment of these rare neoplasms.




TÍTULO / TITLE:  - Management of well-differentiated gastrointestinal neuroendocrine tumors metastatic to the liver.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):69-74. doi: 10.1053/j.seminoncol.2012.11.007.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.007

AUTORES / AUTHORS:  - Wang SC; Fidelman N; Nakakura EK

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Division of Surgical Oncology and UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

RESUMEN / SUMMARY:  - Neuroendocrine tumors (NETs) can have indolent clinical courses and patients with metastatic disease may live many years after the initial diagnosis. Recent studies have suggested that aggressive treatments may extend survival. In this review, we assess the recent literature regarding management of well-differentiated NETs from the gastrointestinal (GI) tract metastatic to the liver. We focus on studies regarding surgical resection, embolization, or ablation of hepatic lesions. We also present a management algorithm for patients  who present with metastatic lesions but the primary lesion cannot be located. Since NETs are rare, all of the available evidence is based on retrospective studies that have limited sample size. As a result, recommendations are offered with caution.




TÍTULO / TITLE:  - The evolving landscape of neuroendocrine tumors.

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

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):4-22. doi: 10.1053/j.seminoncol.2012.11.013.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.013

AUTORES / AUTHORS:  - Bergsland EK

INSTITUCIÓN / INSTITUTION:  - UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94115, USA. emilyb@medicine.ucsf.edu

RESUMEN / SUMMARY:  - Neuroendocrine tumors (NET) encompass a heterogeneous group of tumors demonstrating varied clinical behavior. The field has recently witnessed several  important developments stemming from improvements in histopathological classification schemes, advanced imaging techniques, and a deeper understanding of the molecular mechanisms underlying tumor progression (in both sporadic and hereditary cancers). Platinum-based chemotherapy remains the mainstay of therapy  for high grade carcinomas. In contrast, the treatment of advanced well-differentiated NET depends on site of origin, underlying tumor biology, and  whether or not the patient is symptomatic. Somatostatin analogs continue to play  a key role in controlling hormone-mediated symptoms. In addition, octreotide has  demonstrated anti-tumor activity in midgut carcinoids. Novel somatostatin analogs (for use alone or in the context of peptide receptor radiotherapy or imaging) are on the horizon. Agents targeting VEGF- and mTOR-pathway signaling have been approved for pancreatic neuroendocrine tumors. In addition, two RET inhibitors have been approved for medullary thyroid cancer, evidence for a fundamentally new treatment paradigm (based on the use of targeted agents). Despite the advances, there remains a serious unmet need for additional treatment options for refractory high-grade neuroendocrine carcinomas, paragangliomas/pheochromocytomas, adrenocortical carcinomas, and progressive carcinoid tumors. Furthermore, the role of liver-directed therapy in the context  of available systemic approaches needs clarification. Steady progress is anticipated, however, given the unprecedented number of ongoing clinical trials related to NET (including studies focused on symptom control, genetics, imaging,  and novel therapies).




TÍTULO / TITLE:  - Two different types of carcinoid tumors of the lung: immunohistochemical and ultrastructural investigation and their histogenetic consideration.

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

REVISTA / JOURNAL:  - Ultrastruct Pathol. 2013 Feb;37(1):23-35. doi: 10.3109/01913123.2012.707962.

            ●● Enlace al texto completo (gratuito o de pago) 3109/01913123.2012.707962


INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Deaconess Hospital, University of Oklahoma, College of Medicine, Oklahoma City, Oklahoma 73112, USA. kyungwhanmin@yahoo.com

RESUMEN / SUMMARY:  - Carcinoid tumors have been an interesting clinical and pathological entity for pathologists because of their unique histopathologic pattern of “Zellballen” (cell ball) and the hormones they produce demonstrable by histochemical and biochemical methods, including immunohistochemistry, and the presence of cytoplasmic dense-core particles demonstrable by electron microscopy. Since carcinoid tumors were established as an entity more than a century ago by Oberndorfer, who was credited with coining the term “carcinoid,” meaning carcinoma-like tumors, tumors presenting with similar characteristics have been reported in most of parenchymal organs, including lungs. Carcinoid tumors in the  lungs usually occur as bronchocentric tumors and present with typical histopathologic characteristics of carcinoid tumors, but they may present with significant variation in their cellular compositions, in contrast to the midgut carcinoid tumors. In the latter, tumor cells are quite similar to enterochromaffin granule containing crypt cells, which are regarded as their progenitor cells. Currently, a similar histogenetic explanation is applied to all carcinoid tumors occurring elsewhere. The bronchus is one of the most common anatomic sites in which the carcinoid tumors occur. However, bronchial carcinoid  tumors differ from the midgut counterparts in microscopic appearance, showing more variability in cellular shape and composition from the classical form of midgut carcinoid tumors. In the lungs, neuroendocrine cells (NEC) are normally found in two different ways. Firstly, they are found as randomly scattered single cells (Kultchitsky cells) similar to enteric counterparts, and, secondly, they are found in aggregates known as “neuroepithelial bodies” (NEB) usually found in  the branching point of bronchi. Interestingly, they keep a close anatomic relationship with parasympathetic nerve structures and even form synapses. NEB are usually found in the early stage of fetal development and are claimed to play an important role in the branching of bronchi and regeneration of bronchial epithelial cells following tissue injury. They are claimed to play an important function as a chemoreceptor apparatus related to oxygen tension of the breathing  air. To test the hypothesis that histopathologic variability found in bronchial carcinoids may be related to the fact that lungs are endowed with more than one type of NEC, the author reviewed 36 cases of bronchial carcinoids and found 8 cases in which tumor cells varied significantly from typical carcinoids in cell shape and arrangement. Tumor cells tend to be spindly with frequent presence of S-100-positive sustentacular cells. The latter was designated as type II carcinoid and the rest as type I. Ultrastructurally, tumor cells in type I exhibited features more typical for epithelial cells. The tumor cells were usually polygonal, forming closely packed cell masses, and cell membranes were closely apposed with frequent primitive cell junctions. The membrane-bound dense-core granules were of variable size and appearance and larger than those seen in type II in which the size of granules ranged from 160 to 350 nm. In 2 cases of type I, frequent cells contained myelin bodies similar to those found in type II alveolar cells. In 14 cases of type I tumors, tumor cells formed lumens into which microvilli were converging. In 5 cases, some areas showed increased cell size exceeding the usual limit of pathologist’s comfortable range of small cells. In 2 cases, the tumor contained areas of adenocarcinoma. Tumor cells in type II were rather oblong and closely packed without any intercellular spaces and the majority of tumor cells contained dense-core granules typical for so-called P granules. These cells seem to give out slender cell processes containing a few dense-core granules. In rare foci, groups of thin cell processes aggregate where profiles of processes cut at different angles can be seen. In such areas one can recognize the profiles of microtubules in many of them. In one tumor, which was previously reported by the author (Ultrapath 2001;25:207), microtubule-containing dendrites were common, as seen esthesioneuroblastomas. They appeared similar to dendrites of neurons. In addition to these chief cells,  there were variable numbers of agranulated cells usually found at the periphery of cell balls bordering the interstitium. Some of these cells contained large aggregates of polymorphic dense bodies. However, no definite premelanosomes were  found in our series. The results indicate that there exist at least two different types of carcinoid tumors in the lungs and their immunohistochemical and ultrastructural characteristics are quite different. The type I tumors are quite  similar to those found in the midgut and their histogenesis might be similar. The type II tumors showed rather definite neural features in their immunophenotypic and ultrastructural characteristics, which is difficult to explain by the same histogenesis applied to type I. We postulate that type II tumors have a different histogenesis from type I. They may derive from NEC of neuroepithelial bodies rather than Kultchitsky cells. In this regard, it is interesting to note the similarity between neuroepithelial bodies of the lungs and olfactory bulbs in their cellular composition and anatomic arrangement of epithelial cells and nerves, and the similarity between tumors they produce, bronchial carcinoid tumors in our type II and olfactory neuroblastomas. It is concluded that there are two types of bronchial carcinoid tumors having two different histogenetic pathways. Detailed analysis of the ultrastructural characteristics is the best and definite means to differentiate two types of pulmonary carcinoid tumors.




TÍTULO / TITLE:  - Recurrent multiple spinal paragangliomas as a manifestation of a metastatic composite paraganglioma-ganglioneuroblastoma.

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

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1678-0

AUTORES / AUTHORS:  - Gempt J; Baldawa SS; Weirich G; Delbridge C; Hempel M; Lohse P; Meyer B; Ringel F

INSTITUCIÓN / INSTITUTION:  - Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Str. 22, 81675, Munchen, Germany, Jens.Gempt@lrz.tum.de.




TÍTULO / TITLE:  - Thyroid cancer in Tuzla region of Bosnia and Herzegovina: a 10-year study (1999-2008).

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:53-7.

AUTORES / AUTHORS:  - Salkic A; Brkic F; Cickusic A; Cickusic E; Altumbabic H

INSTITUCIÓN / INSTITUTION:  - University Clinical Centre Tuzla, Department of ENT Surgery, Tuzla, Bosnia and Herzegovina. almir.salkic@gmail.com

RESUMEN / SUMMARY:  - Bosnia and Herzegovina (B&H) is one of the Eastern European countries with lacking data on thyroid cancer (TC) epidemiology. We aimed to assess the incidence of TC in Tuzla Canton of B&H during a 10-year period (1999-2008). We retrospectively evaluated 65000 hospital records of both inpatients and outpatients with possible thyroid symptoms residing in Tuzla Canton of B&H (total of 496280 inhabitants) between 1999 and 2008. Patients with histological proof of TC were included in study. Incidence rates were calculated with age standardisation using European standard population. Trends in incidence were evaluated as moving three-year averages. During observed period 117 patients met  the diagnostic criteria for TC with male to female ratio of 1:4.85. Median age of all cases was 51 years (interquartile range: 41 to 60) with men in average 9 years older than women at the time of diagnosis. The mean annual standardized incidence was found to be 2.30/10(5) (% 95 CI = 1.38-3.22) inhabitants ranging from 1.0 to 3.2 per 10(5). The average crude incidence in men was 0.82/10(5) and  3.83/10(5) in women. The prevalence of TC, at the end of the observed period was  found to be 23.58/10(5) (% 95 CI = 19.3-27.58). There is a slight decline of incidence in our region during the observed period, but with the increase in the  latest years of the study. This increase is probably the result of combination of various factors, mainly the better detection of new cases due to wider availability of diagnostics. Based on depicted trends, we believe that in the future years, TC incidence in our region will continue to rise.




TÍTULO / TITLE:  - Primary high-grade neuroendocrine carcinoma of the heart.

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

REVISTA / JOURNAL:  - Tex Heart Inst J. 2013;40(1):71-4.

AUTORES / AUTHORS:  - Guajardo-Salinas GE; Anaya-Ayala JE; Rice DC; Moran CA; Reardon MJ

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery (Drs. Guajardo-Salinas, Moran, Reardon, and  Rice), University of Texas MD Anderson Cancer Center; and Department of Cardiovascular Surgery (Drs. Anaya-Ayala, Guajardo-Salinas, and Reardon), Methodist DeBakey Heart & Vascular Center; Houston, Texas 77030.

RESUMEN / SUMMARY:  - We report the successful resection of a solitary, apparently primary, high-grade  neuroendocrine carcinoma of the heart, in a 70-year-old man who had presented with progressive dyspnea. The tumor occupied the right atrium and almost completely obstructed the superior and inferior venae cavae; it also involved the aortic root and the interatrial septum. To postpone the patient’s impending cardiac failure, we resected the gross tumor except in the region of the aortic root and the trigone, which we debulked. We completely reconstructed the right atrium with pericardium and the interatrial septum with a pericardial patch. The  patient recovered uneventfully; 18 months postoperatively, he had experienced only local recurrence in the tumor bed. This case shows that the palliative resection of large neuroendocrine tumors of the heart can yield good outcomes and prolong patient survival. To our knowledge, ours is the only report of a high-grade neuroendocrine cardiac tumor of apparently primary origin to have been resected with good palliative results.




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.




TÍTULO / TITLE:  - MIBG Superscan of Metastatic Paraganglioma Occurring With Neurofibromatosis Type  1.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182816777

AUTORES / AUTHORS:  - Harrison CE; Barron BJ

INSTITUCIÓN / INSTITUTION:  - From the Department of Radiology and Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Emory University, Atlanta, GA.

RESUMEN / SUMMARY:  - A Tc MDP bone superscan occurs when osseous activity is extremely intense and genitourinary and soft tissue activity is not identified. A similar phenomenon has been described with metaiodobenzylguanidine (MIBG) in metastatic pheochromocytoma and neuroblastoma. We present a case of metastatic paraganglioma resulting in an MIBG superscan. Neuroendocrine bone metastasis alters the biodistribution of MIBG such that the liver, heart, and urinary bladder are not well visualized. Our case occurred in association with neurofibromatosis type 1 and in the absence of an identified primary tumor.




TÍTULO / TITLE:  - Pulmonary Neuroendocrine Tumor Incidentally Detected by 18F-CH PET/CT.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Apr;38(4):e196-9. doi: 10.1097/RLU.0b013e318266cbf1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318266cbf1

AUTORES / AUTHORS:  - Treglia G; Lococo F; Petrone G; Inzani F; Perotti G; Porziella V; Granone P; Rindi G; Giordano A; Rufini V

INSTITUCIÓN / INSTITUTION:  - From the *Institute of Nuclear Medicine and daggerDepartment of Thoracic Surgery; and double daggerInstitute of Pathology, Catholic University of the Sacred Heart, Rome, Italy.

RESUMEN / SUMMARY:  - We report the case of a pulmonary neuroendocrine tumor (NET) incidentally detected by F-CH PET/CT performed during restaging in a 68-year-old patient affected by prostate cancer. To clarify the nature of the pulmonary lesion, the patient underwent a CT-guided biopsy which revealed the presence of a pulmonary NET. A subsequent Ga-DOTANOC PET/CT demonstrated the somatostatin receptor expression in the pulmonary lesion. The patient underwent a right lung lobectomy; at pathology, a well-differentiated NET was confirmed. Our case highlights that pulmonary NETs should be considered in the differential diagnosis of pulmonary lesions showing uptake of radiolabeled choline.




TÍTULO / TITLE:  - Multifocal Extra-Adrenal Paraganglioma Evaluated With Different PET Tracers: Comparison Between 18F-FDG, 18F-DOPA and 68Ga DOTANOC 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.0b013e31827088d9

AUTORES / AUTHORS:  - Treglia G; Cardillo G; Stefanelli A; Di Franco D; Enang GN; Giordano A; Rufini V

INSTITUCIÓN / INSTITUTION:  - From the *Department of Bioimaging and Radiological Sciences, Institute of Nuclear Medicine, Catholic University of the Sacred Heart; and daggerDepartment of Thoracic Surgery, Carlo Forlanini Hospital, Rome, Italy.

RESUMEN / SUMMARY:  - A 40-year-old female patient with suspected multifocal extra-adrenal paraganglioma, on the basis of biochemical, genetic, and conventional imaging data, underwent F-FDG, F-DOPA and Ga DOTANOC PET/CT. FDOPA- and FDG-PET/CT detected a multifocal mediastinal and cervical paraganglioma. Ga-DOTANOC PET/CT detected 2 additional lesions compared to the other PET/CT methods. In our case,  somatostatin receptor PET/CT with Ga-DOTANOC correctly assessed the extent of the disease in a patient with multifocal paraganglioma.




TÍTULO / TITLE:  - Merkel cell carcinoma from 2008 to 2012: Reaching a new level of understanding.

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

REVISTA / JOURNAL:  - Cancer Treat Rev. 2013 Jan 31. pii: S0305-7372(13)00004-2. doi: 10.1016/j.ctrv.2012.12.009.

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

AUTORES / AUTHORS:  - Prieto Munoz I; Pardo Masferrer J; Olivera Vegas J; Medina Montalvo MS; Jover Diaz R; Perez Casas AM

INSTITUCIÓN / INSTITUTION:  - Radiation Oncology Department, Capio Fundacion Jimenez Diaz University Hospital,  Avenida Reyes Catolicos No. 2, 28040 Madrid, España. Electronic address: iprieto@fjd.es.

RESUMEN / SUMMARY:  - Merkel cell carcinoma (MCC) is a rare primary cutaneous carcinoma of the skin who has high aggressiveness, high risk of locoregional and distant spread, a mortality rate considerably higher than that of cutaneous melanoma and a poor survival. Its incidence has increased during the past twenty years. The studies published from 2008 to early 2012 have introduced interesting changes in the understanding of its epidemiology, pathogenesis and consequently in the diagnostic codes and the therapeutic approach. Early and detailed nodal diagnosis with posterior multidisciplinary decision is mandatory. Surgery and Radiotherapy  play a fundamental role in the management of this tumor. Both are associated with improved locoregional control and disease free survival; but patients continue to have distant failure because, currently, there is no effective systemic treatment available. Consequently, there remain controversies about its appropriate management, and this review is an attempt to contribute to their clarification.




TÍTULO / TITLE:  - Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients.

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

REVISTA / JOURNAL:  - Endocr Relat Cancer. 2013 Mar 5.

            ●● Enlace al texto completo (gratuito o de pago) 1530/ERC-12-0223

AUTORES / AUTHORS:  - Hilfenhaus G; Gohrig A; Pape UF; Neumann T; Jann H; Zdunek D; Hess G; Stassen JM; Wiedenmann B; Detjen K; Pavel M; Fischer C

INSTITUCIÓN / INSTITUTION:  - G Hilfenhaus, ECRC, Experimental and Clinical Research Center, a joint cooperation between the Charite Medical Faculty and the Max-Delbruck Center for Molecular Medicine, Berlin, Germany.

RESUMEN / SUMMARY:  - Placental growth factor (PlGF), a VEGF-homolog implicated in tumor angiogenesis and adaptation to antiangiogenic therapy, is emerging as candidate target in malignancies. Here, we addressed the expression, function and prognostic value of PlGF in neuroendocrine tumors (NETs). PlGF was determined in sera of NET patients collected retrospectively (n=88) and prospectively (n=87) using Roche-Elecsys and correlated with clinicopathological data. Tumoral PlGF was evaluated by immunohistochemistry, effects of PlGF on proliferation and migration in vitro were assessed using different NET cell lines and effects on tumor growth in vivo  in orthotopic xenografts. Circulating and tumoral PlGF were elevated in patients  with pancreatic NETs (pNETs) as compared to control sera and respective healthy tissue. De novo PlGF expression occurred primarily in the tumor stroma, suggesting paracrine stimulatory circuits. Indeed, PlGF enhanced NET proliferation and migration in vitro and, conversely, neutralizing antibodies to  PlGF reduced tumor growth in vivo. Elevated circulating PlGF levels in NET patients correlated with advanced tumor grading and were associated with reduced  tumor-related survival in pNETs. Subsequent determinations confirmed and extended our observation of elevated PlGF levels in a prospective cohort of grade 1 and grade 2 pNETs (n=30) and intestinal NETs (n=57). In low-grade pNETs, normal circulating PlGF levels were associated with better survival. In intestinal NETs, circulating PlGF above median emerged as an independent prognostic factor for shorter time-to-progression in multivariate analyses. These data assign to PlGF a novel function in the pathobiology of NETs and propose PlGF as prognostic parameter and therapeutic target.




TÍTULO / TITLE:  - Role of (18)FDG PET/CT in patients treated with (177)Lu-DOTATATE for advanced differentiated neuroendocrine tumours.

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

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-013-2369-z

AUTORES / AUTHORS:  - Severi S; Nanni O; Bodei L; Sansovini M; Ianniello A; Nicoletti S; Scarpi E; Matteucci F; Gilardi L; Paganelli G

INSTITUCIÓN / INSTITUTION:  - Unit of Radiometabolic Medicine, Cancer Institute of Romagna (IRST), Meldola, FC, Italy.

RESUMEN / SUMMARY:  - PURPOSE: The prognostic value of FDG PET for neuroendocrine tumours (NETs) has been reported. In this study we evaluated the role of FDG PET in predicting response and progression-free survival (PFS) after (177)Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced well-differentiated grade ½ NETs. METHODS: We retrospectively evaluated 52 patients with progressive advanced NETs overexpressing somatostatin receptors and treated with Lu-PRRT with a cumulative activity up to 27.7 GBq divided into five  courses. According to WHO 2010/ENETS classification, patients were stratified into two groups: those with grade 1 tumour (Ki-67 index </=2 %, 19 patients), and those with grade 2 tumour (Ki-67 index >3 % to <20 %, 33 patients). On the basis  of the FDG PET scan, 33 patients were classified as PET-positive (PET+) and 19 as PET-negative (PET-). RESULTS: FDG PET was positive in 57 % of patients with grade 1 NET and in 66 % of patients with grade 2 NET, and the rates of disease control  (DC, i.e. complete response + partial response + stable disease) in grade 1 and grade 2 patients were 95 % and 79 %, respectively (P = 0.232). In PET- and PET+ patients, the DC rates were 100 % and 76 % (P = 0.020) with a PFS of 32 and 20 months, respectively (P = 0.033). Of the PET+ patients with grade 1 NET, 91 % showed disease control, whereas about one in three PET+ patients with grade 2 NET (32 %) progressed after Lu-PRRT (DC rate 68 %). CONCLUSION: These results suggest that FDG PET evaluation is useful for predicting response to Lu-PRRT in patients  with grade ½ advanced NETs. Notably, none of PET- patients had progressed at the first follow-up examination after Lu-PRRT. Grade 2 NET and PET+ (arbitrary SUV cutoff >2.5) were frequently associated with more aggressive disease. PET+ patients with grade 2 NET, 32 % of whom did not respond to Lu-PRRT monotherapy, might benefit from more intensive therapy protocols, such as the combination of chemotherapy and PRRT.




TÍTULO / TITLE:  - Genetics of pheochromocytoma and paraganglioma in Spanish pediatric patients.

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

REVISTA / JOURNAL:  - Endocr Relat Cancer. 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1530/ERC-12-0339

AUTORES / AUTHORS:  - Cascon A; Inglada-Perez L; Comino-Mendez I; de Cubas AA; Leton R; Mora J; Marazuela M; Galofre JC; Quesada-Charneco M; Robledo M

INSTITUCIÓN / INSTITUTION:  - A Cascon, Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, España.

RESUMEN / SUMMARY:  - Pheochromocytomas and paragangliomas are neuroendocrine tumors developed in the adrenal medulla and in the extra-adrenal thoraco-abdominal sympathetic and parasympathetic paraganglia, respectively. Although clinical diagnosis of these tumors is infrequent during childhood, there have been reports of pediatric patients either carrying germline alterations in one of ten major pheochromocytoma/paraganglioma susceptibility genes, or without known mutations.  While new PCC/PGL susceptibility genes have recently been identified, little is known regarding their involvement in pediatric tumor development. We discuss here clinical and genetic criteria relevant to management of pheochromocytoma/paraganglioma patients diagnosed before age 18 years. Clinical and genetic data obtained from 36 pediatric non-related probands, tested for alterations in nine major pheochromocytoma/paraganglioma susceptibility genes (VHL, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX), were compared to data obtained from 411 genetically characterized non-pediatric cases. Seventy percent of probands had germline mutations affecting SDHB, SDHD, VHL, RET or MAX, with an over-representation of truncating SDHB mutations in the pediatric cases compared to non-pediatric patients. Amongst cases without mutations, we found a significantly higher proportion of pediatric patients with clinical features (bilateral pheochromocytoma and coexistence of pheochromocytoma and paraganglioma) suggestive of a hereditary condition (p=0.008). Genetic screening  for mutations in the susceptibility genes SDHB, SDHD, VHL, RET and MAX is strongly recommended in children developing PCC/PGL, starting with the metastasis-related gene SDHB. Alterations affecting still unidentified PCC/PGL susceptibility genes are probably responsible for a high proportion of the mutation-negative pediatric cases.




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.




TÍTULO / TITLE:  - High penetrance of pheochromocytoma in multiple endocrine neoplasia 2 caused by germ line RET codon 634 mutation in Japanese patients.

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

REVISTA / JOURNAL:  - Eur J Endocrinol. 2013 Feb 15.

            ●● Enlace al texto completo (gratuito o de pago) 1530/EJE-12-1106

AUTORES / AUTHORS:  - Imai T; Uchino S; Okamoto T; Suzuki SI; Kosugi S; Kikumori T; Sakurai A

INSTITUCIÓN / INSTITUTION:  - T Imai, Breast & Endocrine Surgery, Aichi Medical University, Nagakute, Japan.

RESUMEN / SUMMARY:  - ObjectiveThe precise penetrance of pheochromocytoma (PHEO) in multiple endocrine  neoplasia type 2 (MEN2) has not been reported in a large cohort. In this study we aimed to clarify the codon specific penetrance of PHEO in MEN2.DesignWe established a study group designated the “MEN Consortium of Japan” in 2008, and asked physicians and surgeons to provide clinical and genetic information on patients they had treated up to 2011.MethodsData were collected on patients identified as carriers of the RET mutation or diagnosed with medullary thyroid carcinoma (MTC) and/or PHEO with family history from 52 institutions all over Japan.ResultsOf 493 registered MEN2 patients, RET mutation data was available for 390. Of these, 144 developed PHEOs, while 246 did not. The penetrance of PHEO was 25% by age 30, 52% by age 50, and 88% by age 77 in RET mutation-carriers with a codon 634 mutation. All patients with a codon 918 mutation (MEN2B) developed PHEO by age 56. Less than 32% penetrance of PHEO was seen in patients with mutations at codons other than 634 and 918.ConclusionsMost patients with a codon 634 mutation develop PHEOs as well as MTC during their lifetime.




TÍTULO / TITLE:  - Quality of life is decreased in patients with paragangliomas.

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-12-0968

AUTORES / AUTHORS:  - van Hulsteijn LT; Louisse A; Havekes B; Kaptein AA; Jansen J; Hes FJ; Smit JW; Corssmit EP

INSTITUCIÓN / INSTITUTION:  - L van Hulsteijn, Endocrinology & Metabolic Diseases, Leiden University Medical Center, Leiden, 2333 ZA, Netherlands.

RESUMEN / SUMMARY:  - CONTEXT: Germline mutations in succinate dehydrogenase (SDH) genes predispose carriers for developing paragangliomas and studies on their quality of life (QoL) are scarce. OBJECTIVES: The objectives of this study were to assess QoL in patients with paragangliomas, to evaluate long-term QoL and to explore potential  differences in QoL between SDH-mutation carriers and paraganglioma patients without an SDH-mutation. DESIGN: Cross-sectional, case-control study. SETTING: Tertiary referral center. SUBJECTS: 174 paraganglioma patients were included; 25  SDHB-, 2 SDHC- and 122 SDHD-mutation carriers and 25 patients without an SDH-mutation. They provided 100 peers as control persons. Furthermore, patients were compared to age-adjusted reference populations. MAIN OUTCOME MEASURES: QoL was assessed using three validated health related QoL questionnaires: the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Fatigue Index  (MFI-20) and the Short Form 36 (SF-36). RESULTS: Patients reported a significantly impaired QoL compared to their own controls, mainly on fatigue and  physical condition subscales. Compared to age-adjusted literature values, patients had significantly impaired scores on physical, psychological and social  subscales. A decreased QoL was mainly related to paraganglioma-associated complaints. THERE WAS NO DIFFERENCE IN QOL BETWEEN THE VARIOUS SDH-MUTATION CARRIERS OR PARAGANGLIOMA PATIENTS WITHOUT AN SDH-MUTATION. QOL IN ASYMPTOMATIC MUTATION CARRIERS, I.E. WITHOUT MANIFEST DISEASE, DID NOT DIFFER FROM QOL OF THE  GENERAL POPULATION.LONG-TERM RESULTS IN 41 PATIENTS SHOWED NO ALTERATION IN QOL,  BESIDES A REDUCED LEVEL OF ACTIVITY.CONCLUSION: QoL is decreased in paraganglioma patients, but stable when measured over time.




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.




TÍTULO / TITLE:  - Perioperative Management of a Patient with a Non-Resectable Pheochromocytoma.

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

REVISTA / JOURNAL:  - Endocr Pract. 2013 Feb 20:1-8.

            ●● Enlace al texto completo (gratuito o de pago) 4158/EP12343.CR

AUTORES / AUTHORS:  - Badri M; Gibbons AV; Popii V; Yih D; Cohen-Stein DL; Patel SM

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Lankenau Medical Center, Wynnewood, Pennsylvania.

RESUMEN / SUMMARY:  - Objective: To describe the clinical course of a patient with a non-resectable pheochromocytoma during urgent hip surgery.Methods: To describe the clinical management and postoperative outcome of the patient and review the relevant literature.Results: An 85 year old male with a non-resectable pheochromocytoma required urgent hip surgery following a traumatic hip fracture. To avoid potential pheochromocytoma-related complications, he was managed with phenoxybenzamine, metyrosine and metoprolol perioperatively. He remained hemodynamically stable and recovered from the surgery without complications.Conclusions: This case illustrates the successful management of a patient requiring urgent surgery in the setting of a non-resectable pheochromocytoma, which is rarely described in the literature.




TÍTULO / TITLE:  - White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma.

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

REVISTA / JOURNAL:  - Biochim Biophys Acta. 2013 Feb 20. pii: S1388-1981(13)00044-9. doi: 10.1016/j.bbalip.2013.02.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbalip.2013.02.005

AUTORES / AUTHORS:  - Frontini A; Vitali A; Perugini J; Murano I; Romiti C; Ricquier D; Guerrieri M; Cinti S

INSTITUCIÓN / INSTITUTION:  - Department of Experimental and Clinical Medicine, Center for the Study of Obesity-United Hospitals University of Ancona (Politecnica delle Marche), 60126 Ancona, Italy.

RESUMEN / SUMMARY:  - In all mammals, white adipose tissue (WAT) and brown adipose tissue (BAT) are found together in several fat depots, forming a multi-depot organ. Adrenergic stimulation induces an increase in BAT usually referred to as “browning”. This phenomenon is important because of its potential use in curbing obesity and related disorders; thus, understanding its cellular mechanisms in humans may be useful for the development of new therapeutic strategies. Data in rodents have supported the direct transformation of white into brown adipocytes. Biopsies of pure white omental fat were collected from 12 patients affected by the catecholamine-secreting tumor pheochromocytoma (pheo-patients) and compared with  biopsies from controls. Half of the omental fat samples from pheo-patients contained uncoupling protein 1 (UCP1)-immunoreactive-(ir) multilocular cells that were often arranged in a BAT-like pattern endowed with noradrenergic fibers and dense capillary network. Many UCP1-ir adipocytes showed the characteristic morphology of paucilocular cells, which we have been described as cytological marker of transdifferentiation. Electron microscopy showed increased mitochondrial density in multi- and paucilocular cells and disclosed the presence of perivascular brown adipocyte precursors. Brown fat genes, such as UCP1, PR domain containing 16 (PRDM16) and beta3-adrenoreceptor, were highly expressed in  the omentum of pheo-patients and in those cases without visible morphologic re-arrangement. Of note, the brown determinant PRDM16 was detected by immunohistochemistry only in nuclei of multi- and paucilocular adipocytes. Quantitative electron microscopy and immunohistochemistry for Ki67 suggest an unlikely contribution of proliferative events to the phenomenon. The data support the idea that, in adult humans, white adipocytes of pure white fat that are subjected to adrenergic stimulation are able to undergo a process of direct transformation into brown adipocytes. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.




TÍTULO / TITLE:  - Radioactive Iodine in the treatment of Medullary Thyroid Carcinoma: a controlled  multicenter study.

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

REVISTA / JOURNAL:  - Eur J Endocrinol. 2013 Mar 5.

            ●● Enlace al texto completo (gratuito o de pago) 1530/EJE-12-0943

AUTORES / AUTHORS:  - Meijer JA; Bakker L; Valk GD; de Herder W; de Wilt H; Netea-Maier RT; Schaper N; Fliers E; Lips P; Plukker J; Links T; Smit JW

INSTITUCIÓN / INSTITUTION:  - J Meijer, Internal Medicine, Albert Schweitzer hospital, Dordrecht, 3318 AT, Netherlands.

RESUMEN / SUMMARY:  - ABSTRACTOBJECTIVE: Radioactive iodine (RAI) therapy in medullary thyroid carcinoma (MTC) is applied in some centers, based on the assumption that cross-irradiation from thyroid follicular cells may be beneficial. However, no systematic studies on the effect of RAI treatment in MTC have been performed. The aim of this study was to analyse the effect of RAI treatment on survival in MTC patients. DESIGN: Retrospective multicenter study in 8 University Medical Centers in the Netherlands. METHODS: 293 MTC patients without distant metastases who had  undergone a total thyroidectomy were included between 1980 and 2007. Patients were stratified by clinical appearance, hereditary stage, screening status, and localization. All patients underwent regular surgical treatment with additional RAI treatment in 61 patients. Main outcome measures were disease free survival (DFS) and disease specific survival (DSS). Cure was defined as biochemical and radiological absence of disease. RESULTS: In multivariate analysis stratification according to clinical appearance (p= 0.72), hereditary stage (p= 0.96), localization (p= 0.69), and screening status (p= 0.31) revealed no significant effects of RAI treatment on DFS. Multivariate analysis showed no significant difference in DSS for the two groups stratified according to clinical appearance  (p=0.14). Due to limited number of events, multivariate analysis was not possible for DSS in the other groups of stratification. CONCLUSIONS: Based on the results  of the present analysis, we conclude that RAI has no place in the treatment of MTC.




TÍTULO / TITLE:  - The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours.

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

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-012-2330-6

AUTORES / AUTHORS:  - Zaknun JJ; Bodei L; Mueller-Brand J; Pavel ME; Baum RP; Horsch D; O’Dorisio MS; O’Dorisiol TM; Howe JR; Cremonesi M; Kwekkeboom DJ

INSTITUCIÓN / INSTITUTION:  - Nuclear Medicine Section, Division of Human Health, International Atomic Energy Agency, IAEA, Vienna, Austria, J.zaknun@hotmail.com.

RESUMEN / SUMMARY:  - Peptide receptor radionuclide therapy (PRRNT) is a molecularly targeted radiation therapy involving the systemic administration of a radiolabelled peptide designed to target with high affinity and specificity receptors overexpressed on tumours.  PRRNT employing the radiotagged somatostatin receptor agonists (90)Y-DOTATOC ([(90)Y-DOTA(0),Tyr(3)]-octreotide) or (177)Lu-DOTATATE ([(177)Lu-DOTA(0),Tyr(3),Thr(8)]-octreotide or [(177)Lu-DOTA(0),Tyr(3)]-octreotate) have been successfully used for the past 15  years to target metastatic or inoperable neuroendocrine tumours expressing the somatostatin receptor subtype 2. Accumulated evidence from clinical experience indicates that these tumours can be subjected to a high absorbed dose which leads to partial or complete objective responses in up to 30 % of treated patients. Survival analyses indicate that patients presenting with high tumour receptor expression at study entry and receiving (177)Lu-DOTATATE or (90)Y-DOTATOC treatment show significantly higher objective responses, leading to longer survival and improved quality of life. Side effects of PRRNT are typically seen in the kidneys and bone marrow. These, however, are usually mild provided adequate protective measures are undertaken. Despite the large body of evidence regarding efficacy and clinical safety, PRRNT is still considered an investigational treatment and its implementation must comply with national legislation, and ethical guidelines concerning human therapeutic investigations.  This guidance was formulated based on recent literature and leading experts’ opinions. It covers the rationale, indications and contraindications for PRRNT, assessment of treatment response and patient follow-up. This document is aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRNT and to deliver the treatment in a safe and effective manner. This document  is largely based on the book published through a joint international effort under the auspices of the Nuclear Medicine Section of the International Atomic Energy Agency.




TÍTULO / TITLE:  - Difficulties in the diagnosis of thyroid paraganglioma: a clinical case.

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

REVISTA / JOURNAL:  - Clin Ter. 2013 Jan;164(1):e35-9. doi: 10.7417/CT.2013.1519.

AUTORES / AUTHORS:  - Calo PG; Lai ML; Guaitoli E; Pisano G; Favoriti P; Nicolosi A; Pinna G; Sorrenti S

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Sciences, University of Cagliari; A.O.U. Presidio di Monserrato, Cagliari; Department of Surgical Sciences, Sapienza, University of Rome; Endocrinology, Nuova casa di cura Decimomannu, Cagliari, Italy.

RESUMEN / SUMMARY:  - Thyroid Paragangliomas are exceptionally rare tumors and only 35 documented cases have been reported in the literature. We report an additional unusual male case of thyroid Paraganglioma associated to a chronic lymphocytic thyroiditis and a papillary microcarcinoma. A 45-year-old man presented with a solitary thyroid nodule. Physical examination revealed a smooth, well-circumscribed, firm, mobile, painless thyroid nodule in the right lobe measuring 3 cm. Ultrasound examination  showed a 40 mm hypoechoic, non-homogeneous nodule with peri- and intra-nodular vascular flow. An ultrasound-guided fine needle aspiration biopsy was performed showing the presence of atypical cells (Thy 3). He underwent a total thyroidectomy associated to VI level lymphectomy. Histology showed a thyroid Paraganglioma associated to a chronic lymphocytic thyroiditis and a papillary microcarcinoma measuring 0.3 cm in the greatest dimension. Thyroid Paraganglioma  is an elusive tumor. It is difficult to diagnose and should be included in the differential diagnosis of all neuroendocrine tumors of the thyroid, even those arising in men or behaving in a locally aggressive fashion. Clin Ter 2013; 164(1):e35-39. doi:10.7417/CT.2013.1519.




TÍTULO / TITLE:  - Spontaneous resolution of pituitary apoplexy in a giant boy under 10 years old.

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

REVISTA / JOURNAL:  - J Pediatr Endocrinol Metab. 2012;25(11-12):1177-9.

AUTORES / AUTHORS:  - Chentli F; Bey A; Belhimer F; Azzoug S

INSTITUCIÓN / INSTITUTION:  - Department of Endocrine, and Metabolic Diseases, Bab El Oued University Hospital, Algiers, Algeria. endofarida@hotamail.fr

RESUMEN / SUMMARY:  - AIM: Pituitary gigantism is a very rare condition; the occurrence of pituitary apoplexy in children younger than 10 years old is even rarer. The aim of our study is to report this exceptional association. OBSERVATION: A boy aged 9 years  and 6 months was hospitalized for the first time in November 2011 for symptoms suggesting pituitary apoplexy. The onset of his disease was difficult to determine as his health record has been poorly maintained. On October 10, 2011, he presented to an emergency department with a sudden drop of visual acuity with  diplopia and retro-orbital headaches. An ophthalmological exam found very low visual acuity (1/20) with papillary edema. An MRI of the patient’s brain revealed a hemorrhagic pituitary process reaching the chiasma, which was compressed, especially on the right side. Thereafter, the patient’s vision improved spontaneously. Clinical examination was normal except for gigantism (+5 SD compared to the target stature). Hormonal assessment argued for mixed secretion [growth hormone (GH) = 39 ng/mL, n </= 5, prolactin ( PRL) = 470 ng/mL, n < 15].  Other pituitary functions were normal. Visual acuity normalized after 2 months, and an MRI showed a spontaneous reduction of the pituitary tumor. CONCLUSION: This unusual observation is a model of symptomatic pituitary apoplexy with spontaneous resolution in a boy with pituitary gigantism: phenomenon quite exceptional and worth to be reported.




TÍTULO / TITLE:  - Familial Risk of Small Intestinal Carcinoid and Adenocarcinoma.

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

REVISTA / JOURNAL:  - Clin Gastroenterol Hepatol. 2013 Mar 15. pii: S1542-3565(13)00314-5. doi: 10.1016/j.cgh.2013.02.025.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cgh.2013.02.025

AUTORES / AUTHORS:  - Kharazmi E; Pukkala E; Sundquist K; Hemminki K

INSTITUCIÓN / INSTITUTION:  - Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. Electronic address: e.kharazmi@dkfz.de.

RESUMEN / SUMMARY:  - BACKGROUND & AIMS: Small intestinal cancer (SIC) is rare and its etiology is poorly understood. We compared clusters of families with SICs of different histologic subtypes. METHODS: By using the nationwide family cancer data sets of  Sweden and Finland, we identified a cohort of 9964 first-degree relatives of 1799 patients with SIC, diagnosed from 1961 through 2009. Data were collected from time periods as long as 47 years (mean, 35.4 y) and cancer incidence was determined. Standardized incidence ratios (SIRs) were calculated and stratified by sex, age, time period, and cancer type, using the incidence rates for the entire national population as the reference. RESULTS: Among the 1799 SIC cases, 1.1% had a sibling with SIC, so the SIR was 11.8 (95% confidence interval [CI], 7.2-18.2); 1.1% had a parent or child with SIC (SIR, 3.5; 95% CI, 2.0-5.6). The SIR of concordant carcinoid histology of SIC among siblings was 28.4 (95% CI, 14.7-49.6; n = 12) and in parent-child pairs was 9.9 (95% CI, 5.4-16.6; n = 14).  The familial risk of concordant histologic subtypes increased for siblings diagnosed with adenocarcinoma, but only 2 familial cases were identified. In family members of patients with SIC of the adenocarcinoma subtype, risks of colorectal and bladder cancer were modestly but significantly increased compared  with the general population. Family members of patients with SIC of the carcinoid subtype had an increased risk for kidney cancer and polycythemia vera. CONCLUSIONS: Based on data from our population-based study, first-degree relatives of patients with small intestinal carcinoid tumors have developed these tumors with high incidence. Because of the rareness of this tumor, the absolute risk remains moderate even within families. Gastroenterologists could inform patients with small intestinal carcinoids about the familial risk and encourage counseling for their first-degree relatives. Studies are needed to identify genetic factors that affect susceptibility to SIC.




TÍTULO / TITLE:  - In vivo and in vitro oncogenic effects of HIF2A mutations in pheochromocytomas and paragangliomas.

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

REVISTA / JOURNAL:  - Endocr Relat Cancer. 2013 Mar 26.

            ●● Enlace al texto completo (gratuito o de pago) 1530/ERC-13-0101

AUTORES / AUTHORS:  - Toledo RA; Qin Y; Srikantan S; Morales NP; Li Q; Deng Y; Kim S; Pereira MA; Toledo SP; Su X; Aguiar RC; Dahia P

INSTITUCIÓN / INSTITUTION:  - R Toledo, Medicine, UTHSCSA, San Antonio, United States.

RESUMEN / SUMMARY:  - Pheochromocytomas and paragangliomas are highly vascular tumors of the autonomic  nervous system. Germline mutations, including those in hypoxia-related genes, occur in one-third of the cases, but somatic mutations are rare in these tumors.  Using exome sequencing of 6 paired constitutive and tumor DNA from sporadic pheochromocytomas and paragangliomas, we identified a somatic mutation in the HIF2A (EPAS1) gene. Screening of an additional 239 pheochromocytomas/paragangliomas uncovered three other HIF2A variants in sporadic (4/167, 2.3%), but not in hereditary tumors or controls. Three of the mutations involved proline 531, one of the two residues that controls HIF2alpha stability by hydroxylation. The fourth mutation, on Ser71, was adjacent to the DNA binding  domain. No mutations were detected in the homologous regions of the HIF1A gene in 132 tumors. Mutant HIF2A tumors had increased expression of HIF2alpha target genes, suggesting an activating effect of the mutations. Ectopically expressed HIF2alpha mutants in HEK293, renal cell carcinoma 786-0 or rat pheochromocytoma PC12 cell lines showed increased stability, resistance to VHL-mediated degradation, target induction and reduced chromaffin cell differentiation. Furthermore, mice injected with cells expressing mutant HIF2A developed tumors, and those with Pro531Thr- and Pro531Ser mutations had shorter latency than tumors from mice with wild-type HIF2A. Our results support a direct oncogenic role for HIF2A in human neoplasia and strengthen the link between hypoxic pathways and pheochromocytomas and paragangliomas.




TÍTULO / TITLE:  - Emerging and Mechanism-Based Therapies for Recurrent or Metastatic Merkel Cell Carcinoma.

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

REVISTA / JOURNAL:  - Curr Treat Options Oncol. 2013 Feb 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11864-013-0225-9

AUTORES / AUTHORS:  - Miller NJ; Bhatia S; Parvathaneni U; Iyer JG; Nghiem P

INSTITUCIÓN / INSTITUTION:  - Departments of Medicine/Dermatology, Pathology, University of Washington, 850 Republican Street, Seattle, WA, 98109, USA, njmiller@uw.edu.

RESUMEN / SUMMARY:  - OPINION STATEMENT: Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer with a disease-specific mortality of approximately 40  %. The association of MCC with a recently discovered polyomavirus, combined with  the increased incidence and mortality of MCC among immunocompromised patients, highlight the importance of the immune system in controlling this cancer. Initial management of MCC is summarized within the NCCN guidelines and in recently published reviews. The high rate of recurrent and metastatic disease progression  in MCC, however, presents a major challenge in a cancer that lacks mechanism-based, disease-specific therapies. Traditional treatment approaches have focused on cytotoxic chemotherapy that, despite frequent initial efficacy, rarely provides durable responses and has high morbidity among the elderly. In addition, the immunosuppressive nature of chemotherapy is of concern when treating a virus-associated cancer for which survival is unusually tightly linked to immune function. With a median survival of 9.6 months after development of an  initial metastasis (n = 179, described herein), and no FDA-approved agents for this cancer, there is an urgent need for more effective treatments. We review diverse management options for patients with advanced MCC, with a focus on emerging and mechanism-based therapies, some of which specifically target persistently expressed viral antigens. These treatments include single-dose radiation and novel immunotherapies, some of which are in clinical trials. Due to their encouraging efficacy, low toxicity, and lack of immune suppression, these therapies may offer viable alternatives to traditional cytotoxic chemotherapy.




TÍTULO / TITLE:  - Pheochromocytoma treated with 131 i metaiodo.

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

REVISTA / JOURNAL:  - Tunis Med. 2013 Feb;91(2):161-2.

AUTORES / AUTHORS:  - Khiari K; Hadj Ali I; Lakhoua Y; McHirgui N; Hammami H; Ben Abdallah N




TÍTULO / TITLE:  - Combined partial cystectomy and cesarean delivery in a pregnant female with bladder pheochromocytoma.

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

REVISTA / JOURNAL:  - Can J Urol. 2013 Feb;20(1):6646-8.

AUTORES / AUTHORS:  - Hsi RS; Welty CJ; Sorensen MD; Koreishi AF; Wessells H

INSTITUCIÓN / INSTITUTION:  - Department of Urology, University of Washington School of Medicine, Seattle, Washington 98195, USA.

RESUMEN / SUMMARY:  - We report the first known case of concurrent partial cystectomy and cesarean delivery in a pregnant female with bladder pheochromocytoma. A 28-year-old G4P2 female presented at 28 weeks gestation with labile blood pressures requiring three antihypertensive medications. Urinary catecholamines were elevated, and a subsequent MRI showed a 2.6 cm x 3.2 cm bladder wall mass. She underwent combined cesarian section and partial cystectomy at 37 weeks. Fluid resuscitation and vasopressors were required in the immediate postoperative period. While bladder pheochromocytoma with pregnancy is a rare occurrence, concurrent delivery and removal of the bladder tumor can be performed safely.




TÍTULO / TITLE:  - Pheochromocytoma in ectopic pregnancy: a case report.

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

REVISTA / JOURNAL:  - Clin Exp Obstet Gynecol. 2012;39(4):553-5.

AUTORES / AUTHORS:  - Le A; Shang L; Xiao T; Zhuo R; Wang Z

INSTITUCIÓN / INSTITUTION:  - Department of the Gynaecology, The affiliated Shenzhen Nanshan People’s Hospital, Guangdong Medical College, Shenzhen, China. leaiwen@126.com

RESUMEN / SUMMARY:  - OBJECTIVE: To study pregnancy characteristics in women with pheochromocytoma and  to improve awareness of this comorbidity among obstetricians and gynecologists. METHODS: The diagnosis and treatment of a case of ectopic pregnancy with pheochromocytoma is described. RESULTS: The patient was diagnosed with a ruptured left Fallopian tube isthmus due to pregnancy, with comorbid left adrenal pheochromocytoma. CONCLUSION: Ectopic pregnancy with heavy bleeding and elevated  blood pressure is indicative of pheochromocytoma. Measurement of the levels of urinary vanillylmandelic acid and urinary and serum catecholamines, as well as ultrasonography, can help diagnose this comorbidity.




TÍTULO / TITLE:  - Comparison of abdominal MRI with diffusion-weighted imaging to Ga-DOTATATE PET/CT in detection of neuroendocrine tumors of the pancreas.

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

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2013 Mar 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-013-2371-5

AUTORES / AUTHORS:  - Schmid-Tannwald C; Schmid-Tannwald CM; Morelli JN; Neumann R; Haug AR; Jansen N; Nikolaou K; Schramm N; Reiser MF; Rist C

INSTITUCIÓN / INSTITUTION:  - Institute for Clinical Radiology, Ludwig Maximilians University Hospital Munich,  Marchioninistr. 15, 81377, Munich, Germany.

RESUMEN / SUMMARY:  - PURPOSE: The aim of the study was to evaluate contrast-enhanced MRI, diffusion-weighted MRI (DW MRI), and 68Ga-DOTATATE positron emission tomography (PET)/CT in the detection of intermediate to well-differentiated neuroendocrine tumors (NET) of the pancreas. METHODS: Eighteen patients with pathologically proven pancreatic NET who underwent MRI including DW MRI and PET/CT within 6 weeks of each other were included in this retrospective study. Two radiologists evaluated T2-weighted (T2w), T2w + DW MRI, T2w + contrast-enhanced T1-weighted (CE T1w) MR images, and PET/CT for NET detection. The sensitivity and level of diagnostic confidence were compared among modalities using McNemar’s test and a Wilcoxon signed rank test. Apparent diffusion coefficients (ADC) of pancreatic NETs and normal pancreatic tissue were compared with Student’s t test. RESULTS: Of the NETs, 8/23 (34.8 %) and 9/23 (39.1 %) were detected on T2w images by observers 1 and 2, respectively. Detection rates improved significantly by combining T2w images with DW MRI (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05) or CE T1w images (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05). Detection rates of pancreatic NET with PET/CT (both observers: 23/23 = 100 %) were statistically significantly higher than with MRI (p < 0.05).  The mean ADC value of NET (1.02 +/- 0.26 x 10-3 mm2/s) was statistically significantly lower than that of normal pancreatic tissue (1.48 +/- 0.39 x 10-3 mm2/s). CONCLUSION: DW MRI is a valuable adjunct to T2w imaging and comparable to CE T1w imaging in pancreatic NET detection, quantitatively differentiating between NET and normal pancreatic tissue with ADC measurements. 68Ga-DOTATATE PET/CT is more sensitive than MRI in the detection of pancreatic NET.




TÍTULO / TITLE:  - Small Cell Neuroendocrine Carcinoma Masquerading as Cellulitis and Causing Blindness via Bilateral Orbital Involvement.

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

REVISTA / JOURNAL:  - Orbit. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 3109/01676830.2013.772209

AUTORES / AUTHORS:  - Atik A; Krilis M; Shannon K

INSTITUCIÓN / INSTITUTION:  - Royal Prince Alfred Hospital, Medical Teaching and Administration Unit , Missenden Road, Camperdown , 2050 Australia.

RESUMEN / SUMMARY:  - ABSTRACT Case report: We report the first case of small cell neuroendocrine carcinoma involving both orbits and causing complete blindness. The patient was initially prescribed antibiotics for right periorbital cellulitis, but magnetic resonance imaging demonstrated abnormal enhancing tissue in the superomedial and  superior right orbit with destruction of the anterior lamina papyracea, extension into the anterior ethmoid air cells, further extension into the right frontal bone and pockets of fluid in the right frontal lobe. Histopathology from the orbital tissue and right frontal subdural empyema demonstrated small cell neuroendocrine carcinoma of ‘small blue cell’ subtype. The patient received multidisciplinary treatment combining surgery, chemotherapy (both systemic and intra-arterial) and radiotherapy but passed away in the second year of treatment. Comment: Primary small cell neuroendocrine carcinoma is an extremely rare tumour, most frequently occurring in the lungs. An understanding of the pathology has been difficult, due to its rarity and the complexity of the histological diagnosis. Neuroendocrine carcinoma has a very poor prognosis and further research is required for more effective treatment options.




TÍTULO / TITLE:  - A Large Cell Neuroendocrine Carcinoma of the Gall Bladder: Diagnosis with 18FDG-PET/CT-guided Biliary Cytology and Treatment with Combined Chemotherapy Achieved a Long-term Stable Condition.

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

REVISTA / JOURNAL:  - Jpn J Clin Oncol. 2013 Mar 26.

            ●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hyt033

AUTORES / AUTHORS:  - Okuyama Y; Fukui A; Enoki Y; Morishita H; Yoshida N; Fujimoto S

INSTITUCIÓN / INSTITUTION:  - 1Department of Gastroenterology, Japan Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.

RESUMEN / SUMMARY:  - Poorly differentiated neuroendocrine cell carcinomas of the gallbladder are rare  and patients with such tumors have a poor prognosis. We describe a 64-year-old male with a large cell neuroendocrine carcinoma of the gallbladder and multiple lymph node metastases. Diagnostic excisional biopsy of the left axillary lymph nodes revealed atypical cells with predominantly large-sized round-to-oval nuclei, proliferating in a solid and focal nesting pattern. The tumor cells were  positive for synaptophysin and chromogranin A, and strongly positive for Ki-67, leading to a diagnosis of poorly differentiated neuroendocrine cell carcinoma of  the gallbladder, of large cell type. Using 18F-fluorodeoxy glucose-positron emission tomography/computed tomography to determine the origin of these tumors,  we observed the accumulation of 18F-fluorodeoxy glucose in multiple large lymph nodes, a small part of the liver and the fundus of the gallbladder. Computed tomography-guided aspiration of the gallbladder showed the same pleomorphic tumor cells as the lymph nodes. The patient was diagnosed with a large cell neuroendocrine carcinoma of the gallbladder, only approximately 25 mm in diameter. Combination chemotherapy with cisplatin and docetaxel, the regimen used for non-small cell lung carcinomas, and probably large cell lung carcinomas, resulted in the disappearance of the lymph node metastases and a marked improvement in the performance status for approximately 22 months. The poor prognosis of patients with these aggressive tumors may be improved by the use of  minimally invasive diagnostic procedures and combined systemic chemotherapy as soon as possible.




TÍTULO / TITLE:  - A rare case of merkel cell carcinoma metastasis to the adrenal resected robotically.

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

REVISTA / JOURNAL:  - Surg Laparosc Endosc Percutan Tech. 2013 Feb;23(1):e35-7. doi: 10.1097/SLE.0b013e31827479a1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SLE.0b013e31827479a1

AUTORES / AUTHORS:  - Alguraan Z; Agcaoglu O; Aliyev S; Berber E

INSTITUCIÓN / INSTITUTION:  - Endocrinology and Metabolism Institute, Division of Endocrine Surgery, Cleveland  Clinic, Cleveland, OH, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: Merkel cell carcinoma (MCC) is an uncommon skin malignancy that has a high propensity for metastatic spread and there is no consensus regarding the optimal therapeutic approach. The relative roles of surgery, radiotherapy, and chemotherapy are still controversial. As the robotic approaches are gaining more  popularity over the recent years, herein we report our result for MCC using robotics. METHODS: We herein describe a patient with MCC metastases to the left adrenal gland, which was resected robotically. The procedure was performed under  general anesthesia using the robotic camera and 2 robotic working ports. RESULTS: A 59-year-old woman, who was diagnosed to have MCC of the left forearm 1 year ago with stage T2 N1 and removed by wide excision, underwent left robotic lateral transabdominal adrenalectomy because of MCC metastasis to the left adrenal gland. She was discharged home on postoperative day 2 uneventfully and is currently alive at 18 months with no evidence of recurrent disease on imaging studies. CONCLUSIONS: This case report demonstrates that minimally invasive adrenalectomy  may be performed for isolated MCC metastasis.




TÍTULO / TITLE:  - High incidence of extraadrenal paraganglioma in families with SDHx syndromes detected by functional imaging with [(18)F]fluorodihydroxyphenylalanine PET.

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

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2013 Feb 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-013-2346-6

AUTORES / AUTHORS:  - Miederer M; Fottner C; Rossmann H; Helisch A; Papaspyrou K; Bartsch O; Mann WJ; Musholt TJ; Weber MM; Lackner KJ; Schreckenberger M

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, University Medical Centre of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany, Matthias.miederer@unimedizin-mainz.de.

RESUMEN / SUMMARY:  - PURPOSE: Knowledge of the genetic backgrounds of hereditary syndromes, which are  increasingly being characterized, enables genetic screening of family members of  affected patients. Upon detection of a mutation, genetic counselling and clinical screening including imaging modalities and biochemical analyses are commonly performed. METHODS: Unaffected, mutation-positive relatives of index patients with hereditary paraganglioma syndromes were offered PET imaging with [(18)F]fluorodihydroxyphenylalanine and the incidence of pathological findings was retrospectively analysed in relation to mutations of the succinate dehydrogenase enzyme complex. PET only or PET/CT was performed in 21 individuals  from eight families with SDHD, one family with SDHC and two families with SDHB mutations. Screening was offered every 2 to 5 years. RESULTS: Of the 21 individuals, 14 showed paraganglioma during screening. In particular, in only 2 of 15 patients with a SDHD mutation were the findings completely unremarkable on  PET screening. However, false-negative lesions for abdominal manifestations in two SDHD-positive patients were detected. CONCLUSION: FDOPA PET is a sensitive imaging modality which should be offered to patients with a detected SDHx (SDHD)  mutation, preferably using a hybrid technique.





TÍTULO / TITLE:Phaochromozytomkrise mit kardiogenem Schock.

TÍTULO / TITLE:  - Pheochromocytoma crisis presenting with cardiogenic shock.

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

REVISTA / JOURNAL:  - Herz. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00059-013-3778-2

AUTORES / AUTHORS:  - Chatzizisis YS; Ziakas A; Feloukidis C; Paramythiotis D; Hadjimiltiades S; Iliadis A; Basdanis G; Styliadis I

INSTITUCIÓN / INSTITUTION:  - First Department of Cardiology, AHEPA University Hospital, Aristotle University Medical School, 1 Stilponos Kyriakidi Street, 54636, Thessaloniki, Greece, joc@med.auth.gr.

RESUMEN / SUMMARY:  - Pheochromocytoma is a catecholamine-secreting tumor of the adrenal glands whose typical presentation includes the triad of headache, palpitations, and diaphoresis. Pheochromocytoma crisis is an urgent medical condition whose diagnosis and management constitute a challenge for physicians. We present the case of a 55-year-old man who developed cardiogenic shock in the setting of a pheochromocytoma crisis. After stabilizing blood pressure with combined administration of alpha- and beta-blockers, the tumor was surgically removed. Our diagnostic and therapeutic challenges are discussed.




TÍTULO / TITLE:  - (18)F-Fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type.

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

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2013 Feb 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-013-2342-x

AUTORES / AUTHORS:  - Balogova S; Talbot JN; Nataf V; Michaud L; Huchet V; Kerrou K; Montravers F

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Comenius University & St. Elisabeth Institute, Heydukova 10, 812 50, Bratislava, Slovakia, sona.balogova@tnn.aphp.fr.

RESUMEN / SUMMARY:  - 6-Fluoro-((18)F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, (123)I-metaiodobenzylguanidine (MIBG) and (111)In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with  a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1-77.6] for FDOPA vs 44 % (95 % CI 35-53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4-97.1) for FDOPA vs 69 % (95 % CI 60.2-77.1) for (123)I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3-95.3) for FDOPA vs 80 % (95 % CI 69.2-88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity  (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in  some rare NET, such as small cell prostate cancer, or in emerging indications, such as metastatic NET of unknown primary (CUP-NET) or adrenocorticotropic hormone (ACTH) ectopic production. An evidence-based strategy in NET functional imaging is as yet affected by a low number of comparative studies. Then the suggested diagnostic trees, being a consequence of the analysis of present data,  could be modified, for some indications, by a wider experience mainly involving face-to-face studies comparing FDOPA and (68)Ga-labelled peptides.




TÍTULO / TITLE:  - Pharmacotherapy of Zollinger-Ellison syndrome.

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

REVISTA / JOURNAL:  - Expert Opin Pharmacother. 2013 Feb;14(3):307-21. doi: 10.1517/14656566.2013.767332. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1517/14656566.2013.767332

AUTORES / AUTHORS:  - Ito T; Igarashi H; Uehara H; Jensen RT

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

RESUMEN / SUMMARY:  - INTRODUCTION: The role of pharmacotherapy in the management of patients with Zollinger-Ellison syndrome (ZES) is often equated with the medical management of  acid hypersecretion. However, pharmacotherapy is also increasingly involved in the other management areas of these patients. AREAS COVERED: This paper reviews the role of pharmacotherapy in all aspects of the management of patients with ZES. Newer aspects are emphasized. This includes the difficulty of diagnosing ZES in patients taking proton pump inhibitors. Also covered is the role of pharmacotherapy in controlling acid hypersecretion and other hormonal hypersecretory states these patients may develop, including hyperparathyroidism in patients with multiple endocrine neoplasia type 1 and ZES; tumor localization; and the treatment of advanced metastatic disease. The last includes chemotherapy, liver-directed therapies, biotherapy (somatostatin/interferon), peptide radio-receptor therapy and molecular-targeted therapies including the use of mTor inhibitors (everolimus) and tyrosine kinase inhibitors (sunitinib). EXPERT OPINION: Pharmacotherapy is now involved in all aspects of the management of patients with ZES, with the result that ZES has progressed from being considered  an entirely surgical disease initially to the present where medical treatment plays a major role in almost all aspects of the management of these patients.




TÍTULO / TITLE:  - Sentinel lymph node in Merkel cell carcinoma: To biopsy or not to biopsy?

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

REVISTA / JOURNAL:  - J Dermatol. 2013 Feb 18. doi: 10.1111/1346-8138.12072.

            ●● Enlace al texto completo (gratuito o de pago) 1111/1346-8138.12072

AUTORES / AUTHORS:  - Sattler E; Geimer T; Sick I; Flaig MJ; Ruzicka T; Berking C; Kunte C

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology and Allergology, Ludwig-Maximilian University of Munich, Munich, Germany.

RESUMEN / SUMMARY:  - Sentinel lymph node biopsy (SLNB) is commonly recommended for patients with primary Merkel cell carcinoma (MCC). However, it is critically discussed whether  survival rates improve by SLNB in MCC patients in general or in subgroups of higher risk (e.g. with primary tumor size >1 cm). The present study correlates clinical data, histology and lymph node status with follow-up and survival data to see if subgroups can be identified for modification of the current recommendations. The medical records of 47 patients with histologically confirmed MCC treated between 1995 and 2010 at a German dermatosurgery department were reviewed. Nineteen patients with excision of the primary tumor and SLNB were compared to 28 patients with excision of the primary tumor but without SLNB. End-points of this study were disease-free survival (DFS) and overall survival (OS). In addition, clinical course was correlated with tumor size and size of safety margin. The group of patients who received SLNB showed a significant advantage in terms of OS (P < 0.05), but not in terms of DFS. Tumors of smaller size were associated with a significantly better DFS and a trend towards better OS. Comparing the groups with different safety margins (1-3 cm), no differences in DFS and OS could be found. Our data support the current recommendation for SLNB in all MCC patients and question the use of extensive safety margins in MCC  surgery. Larger prospective multicenter studies with multivariate analysis are needed to confirm whether a prolonged OS is really due to the SLNB procedure or biased by other factors.




TÍTULO / TITLE:  - Endoscopic Ultrasonography - A Sensitive Tool in the Preoperative Localization of Insulinoma.

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

REVISTA / JOURNAL:  - Endocr Pract. 2013 Feb 20:1-16.

            ●● Enlace al texto completo (gratuito o de pago) 4158/EP12122.OR

AUTORES / AUTHORS:  - Joseph AJ; Kapoor N; Simon EG; Chacko A; Thomas EM; Eapen A; Abraham DT; Jacob PM; Paul T; Rajaratnam S; Thomas N

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Christian Medical College and Hospital, Vellore,  Tamil Nadu, India.

RESUMEN / SUMMARY:  - Objective: A number of imaging modalities have been used in the preoperative localization of insulinomas. CT is the modality that is in widespread use. Endoscopic ultrasound (EUS) allows the transducer to be placed in close proximity to the pancreas, thereby yielding images of higher quality, leading to accurate localization. An accurate preoperative localization results in minimal invasive surgery and a lower occurrence of residual tumours translating into a better clinical outcome.Methods: We analyzed the hospital records of all adult patients  (age > 18 yrs), who were diagnosed to have insulinoma, over a period of 6 yrs, from Oct 2004 to Sept 2010. The diagnosis was based on the clinical practice guidelines of the American Endocrine Society. The sensitivity of EUS was compared with MDCT in localization of the lesion.Results: Eighteen patients were seen over a period of 6 years, from 2004 to 2010. EUS was conducted in all 18 patients. Multi-detector CT scans were carried out in 17 patients. EUS had greater sensitivity (89%)in localizing insulinomas in comparison to CT (69%). In this series, the lesions which were missed on CT, but were picked up on EUS were smaller (less than 12 mm, p = <0.001). Lesions which were close to the mesenteric vessels and those located in the head of the pancreas were more likely to be missed on CT.Conclusions: EUS has a greater sensitivity in identifying and localizing insulinomas preoperatively. With increasing availability, the EUS should be part of a preoperative insulinoma workup.




TÍTULO / TITLE:  - Parasitic myomas after laparoscopic-assisted myomectomy in multiple endocrine neoplasia type 1.

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

REVISTA / JOURNAL:  - J Obstet Gynaecol Res. 2013 Mar 17. doi: 10.1111/jog.12009.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jog.12009

AUTORES / AUTHORS:  - Takeda A; Sakurai A; Imoto S; Nakamura H

INSTITUCIÓN / INSTITUTION:  - Department of Obstetrics and Gynecology, Gifu Prefectural Tajimi Hospital, Tajimi, Japan.

RESUMEN / SUMMARY:  - Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disorder that develops multiple tumors arising from various endocrine  organs, including the parathyroid gland, endocrine pancreas and pituitary gland.  Although mesenchymal tumors can be an integral part of the syndrome, parasitic peritoneal myomas have never been described in an MEN1 patient. Seven years after laparoscopic-assisted myomectomy, parasitic peritoneal myomas were diagnosed in a 31-year-old woman with situs inversus totalis and previous history of parathyroid adenoma. Subsequently, MEN1 was clinically diagnosed by identification of endocrine pancreatic, adrenal and pituitary tumors. Genetic analysis revealed a heterozygous germline mutation in the splice donor sequence of intron 6 of the MEN1 gene. Although rare, parasitic peritoneal myomas could potentially be associated with MEN1 syndrome.




TÍTULO / TITLE:  - Neuroendocrine tumours: cracking the epigenetic code.

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

REVISTA / JOURNAL:  - Endocr Relat Cancer. 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1530/ERC-12-0338

AUTORES / AUTHORS:  - Karpathakis A; Dibra H; Thirlwell C

INSTITUCIÓN / INSTITUTION:  - A Karpathakis, Cancer Institute, University College London, London, United Kingdom.

RESUMEN / SUMMARY:  - The field of epigenetics has evolved rapidly over recent years providing insight  into the tumorigenesis of many solid and haematological malignancies. Determination of epigenetic modifications in neuroendocrine tumour (NET) development is imperative if we are to improve our understanding of the biology of this heterogenous group of tumours. Epigenetic marks such as methylation of RASSF1A are frequent findings in NETs of all origins and may be associated with worse prognosis. Micro RNA signatures and histone modifications have been identified which differentiate subtypes of NET and distinguish NET from adenocarcinoma in cases of diagnostic uncertainty. Historically candidate gene driven approaches have yielded limited insight to the epigenetics of NET. Recent  progress has been facilitated by development of high throughput tools including second generation sequencing and arrays for analysis of the ‘epigenome’ of tumour and normal tissue, permitting unbiased approaches such as exome sequencing which  identified mutations of chromatin remodelling genes ATRX/DAXX in 44% of pancreatic NETs. Epigenetic changes are reversible and therefore represent an attractive therapeutic target, to date clinical outcomes of epigenetic therapies  in solid tumours have been disappointing, however in vitro studies on NET are promising and further clinical trials are required to determine utility of this class of novel agents. In this review we perform a comprehensive evaluation of epigenetic changes found in neuroendocrine tumours to date, including rare NETs such as phaeochromocytoma and adrenocortical tumours. We suggest priorities for future research and discuss potential clinical applications and novel therapies.




TÍTULO / TITLE:  - “Leiomyomatoid angiomatous neuroendocrine tumor” (LANT) of the pituitary reflects idiosyncratic angiogenesis in adenomas of the gonadotroph cell lineage.

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

REVISTA / JOURNAL:  - Pathol Res Pract. 2013 Mar;209(3):155-60. doi: 10.1016/j.prp.2013.01.003. Epub 2013 Feb 15.

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

AUTORES / AUTHORS:  - Schurch C; Birrer M; Estella I; Kappeler A; Hewer E; Vajtai I

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Pathology, Institute of Pathology, University of Bern, Switzerland.

RESUMEN / SUMMARY:  - Based on a single-case observation, the descriptive label “leiomyomatoid angiomatous neuroendocrine tumor” (LANT) has been tentatively applied to what was perceived as a possible novel type of dual-lineage pituitary neoplasm with biphasic architecture. We report on two additional examples of an analogous phenomenon encountered in male patients, aged 59 years (Case 1) and 91 years (Case 2). Both tumors were intra- and suprasellar masses, measuring 5.6cmx4.4cmx3.4cm, and 2.7cmx2cmx1.7cm, respectively. Histologically, Case 1 was  an FSH-cell adenoma interwoven by vascularized connective tissue septa that tended to exhibit incremental stages of adventitial overgrowth. The epithelial component of Case 2 corresponded to an LH-cell adenoma, and lay partitioned by a  maze of paucicellular to hyalinized vascular axes. Irrespective of architectural  variations, perivascular spindle cells exhibited immunopositivity for vimentin, muscular actin, and smooth muscle actin. Conversely, negative results were obtained for CD34, EMA, S100 protein, GFAP, and TTF-1. Ultrastructural study failed to reveal metaplastic cell forms involving transitional features between adenohypophyseal-epithelial and mesenchymal-contractile phenotype. We propose that LANT be regarded as a peculiar reflection of maladaptive angiogenesis in some pituitary adenomas, rather than a genuine hybrid neoplasm. While no mechanistic clue is forthcoming to account for this distinctive pattern, hemodynamic strain through direct arterial - rather than portal - supply of the adenoma’s capillary bed may be one such explanatory factor. The apparent predilection of the LANT pattern for macroadenomas of the gonadotroph cell lineage remains unexplained.





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

REVISTA / JOURNAL:  - Eur J Endocrinol. 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1530/EJE-13-0023

AUTORES / AUTHORS:  - Rossi ED; Martini M; Capodimonti S; Straccia P; Cenci T; Lombardi CP; Pontecorvi A; Larocca LM; Fadda G

INSTITUCIÓN / INSTITUTION:  - E Rossi, Anatomic Pathology, Catholic University, Rome, 00168, Italy.

RESUMEN / SUMMARY:  - OBJECTIVE: In the field of Fine Needle Aspiration Cytology (FNAC), the category of suspicious for malignancy (SM) thyroid lesions which bears 55-85% risk of malignant histology, is a challenging topic in which morphology alone is not always able to make a correct diagnosis. Recently, immunocytochemistry (ICC) has  been referred as helpful in differentiating low and high malignant risk lesions and BRAF activating mutations have been identified in a significant amount of papillary thyroid carcinomas (PTC). The introduction of the liquid-based cytology (LBC) may simplify the application of these techniques to thyroid cytology.DESIGN Our aim is to evaluate the diagnostic and prognostic role of both ICC and BRAF mutation for the SM category on LBC.METHODS From October 2010 through June 2011,  113 LBC cytological cases (including 37 SM and 76 PTC) underwent surgery. All cases were studied for BRAF mutation and ICC.RESULTS In detail, ICC resulted positive in 26 (86.6%) histologically malignant SM with 15 of which (40.5%) expressed a BRAF mutation. Overall 63 cases showed a BRAF mutation histological resulting as PTC.Concerning the prognostic role of BRAF mutation for the two categories, we reported a significant correlation with multifocality, nodal involvement and extracapsular invasion (p<0.0001).CONCLUSIONS Special techniques  such as ICC and molecular might be successfully carried out on LBC- processed material. For both categories, ICC is more sensitive whereas BRAF analysis is an  interesting support due to its high specificity adding a prognostic value in both SM and PTCs.




TÍTULO / TITLE:  - Malignant paraganglioma of the thyroid gland with synchronous bilateral carotid body tumors.

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

REVISTA / JOURNAL:  - Ear Nose Throat J. 2013 Feb;92(2):E20-3.

AUTORES / AUTHORS:  - Mohyuddin N; Ferrer K; Patel U

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.

RESUMEN / SUMMARY:  - We describe a case of primary malignant paraganglioma of the thyroid gland that was found in a 55-year-old woman who had undergone surgery for bilateral carotid  body tumors. The paraganglioma was treated with a total thyroidectomy followed by radiation therapy, and the patient was disease-free after more than 2 years of follow-up. Malignant paragangliomas of the thyroid gland are extremely rare. The  diagnosis of malignancy is based on histopathologic findings, tumor behavior, and metastasis. These tumors can be misdiagnosed as other types of thyroid malignancies, thus resulting in less than optimal treatment. A genetic etiology was suspected in our patient.




TÍTULO / TITLE:  - Medullary Thyroid Carcinoma.

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

REVISTA / JOURNAL:  - Endocr Pract. 2013 Mar 19:1-31.

            ●● Enlace al texto completo (gratuito o de pago) 4158/EP12430.RA

AUTORES / AUTHORS:  - Griebeler ML; Gharib H; Thompson GB

INSTITUCIÓN / INSTITUTION:  - Mayo Clinic College of Medicine, Rochester, Minnesota.

RESUMEN / SUMMARY:  - Objective: This review outlines the advances in the diagnosis, genetic testing and the progress in medullary thyroid cancer (MTC) treatment in light of the most recent evidence.Methods: English-language articles of medullary thyroid cancer published up to 2012 were reviewed. The pertinent articles and their references were obtained and those considered relevant were reviewed for inclusion.Results:  Medullary thyroid carcinoma (MTC), an uncommon neuroendocrine malignancy, accounts for 5% of thyroid cancers. MTC presents in the sporadic and also familial form (MEN 2A, MEN 2B or familial MTC syndromes). The familial forms are  secondary to germline mutations in the RET proto-oncogene. Early diagnosis and treatment is paramount. Genetic testing has made possible early detection in asymptomatic carriers and high risk patients, with early or prophylactic surgery  being curative in many. All carriers of a RET mutation should be evaluated and treated surgically for MTC. The primary treatment in all patients diagnosed with  MTC is total thyroidectomy with central lymph node dissection. Calcitonin (Ct) and carcinoembryonic antigen (CEA) levels can be used as prognostic factors and as tumor markers. If elevated, further investigation including imaging modalities may be necessary for evaluation of metastatic disease. Surgery remains the main treatment for local and locally advanced disease.Conclusion: MTC is rare but morbidity and mortality remain high if untreated. Genetic testing should be offered to all patients. Treatment of choice remains total thyroidectomy and central lymph node dissection. Palliative treatment for advanced disease includes surgery, radiation, standard chemotherapy, chemoembolization and, more recently,  targeted therapies (tyrosine kinase inhibitors).




TÍTULO / TITLE:  - Primary Large-cell Neuroendocrine Tumor of the Breast.

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

REVISTA / JOURNAL:  - Breast J. 2013 Mar;19(2):204-6. doi: 10.1111/tbj.12081.

            ●● Enlace al texto completo (gratuito o de pago) 1111/tbj.12081

AUTORES / AUTHORS:  - Hanna MY; Leung E; Rogers C; Pilgrim S

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Queens Hospital, Burton on Trent, UK.




TÍTULO / TITLE:  - Unsuspected pheochromocytoma multisystem crisis: a fatal outcome in a young male  patient.

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

REVISTA / JOURNAL:  - J Assoc Physicians India. 2012 Aug;60:53-6.

AUTORES / AUTHORS:  - Gundgurthi A; Gupta S; Garg MK; Ganguly P; Bhardwaj R

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Army Hospital (Research and Referral), Delhi Cantt.  110010

RESUMEN / SUMMARY:  - Pheochromocytoma is a great mimicker and has varied presentation. It can present  as medical emergency with hypertensive emergencies, acute cardiac event, neurological manifestations, systemic inflammatory response syndrome, acute respiratory distress syndrome, and metabolic emergencies. Here we report a young  individual who after a bout of exercise developed breathlessness and rapidly developed multiorgan failure which was fatal and post mortem examination revealed pheochromocytoma in right adrenal gland. Pheochromocytoma multisystem crisis is discussed.




TÍTULO / TITLE:  - Diagnosis and treatment of multiple endocrine neoplasia type 1 (MEN1).

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

REVISTA / JOURNAL:  - Minerva Endocrinol. 2013 Mar;38(1):17-28.

AUTORES / AUTHORS:  - Gaztambide S; Vazquez F; Castano L

INSTITUCIÓN / INSTITUTION:  - Hospital Universitario Cruces - Ciberer-UPV-EHU, Barakaldo, España - mariasonia.gaztambidesaenz@osakidetza.net.

RESUMEN / SUMMARY:  - Multiple endocrine neoplasia type 1 (MEN1; formerly known as Wermer syndrome) is  a rare disorder characterized by the combined occurrence of two or more tumors involving parathyroid, pancreatic islets and anterior pituitary glands; some other tumors have also been described. In most cases it is inherited in an autosomic dominant manner but it may occur sporadically. The MEN1 gene (MEN1) is  located on chromosome 11q13, it is composed of ten exons that encode a 610 amino  acid protein called menin. Menin, with no homology to any other known protein, interacts with several different proteins and plays an important role in regulation of cell growth, cell cycle, genome stability and synapse plasticity. Familiar MEN1 has a high degree of penetrance with clinical or biochemical manifestations of the disease in 80% and 98%, respectively, by the fifth decade.  Clinical manifestations are related to tumor localizations and their secretory products. Hyperparathyroidism is the most common feature of MEN1 (95% of patients), pancreatic islet tumors or pancreatic NET (neuroendocrine tumor) occur in 40-70% and pituitary tumors in 30-40% of MEN 1 patients. In addition, other tumors, such as adrenal cortical tumors, carcinoid tumors, lipomas, angiofibromas, colagenomas and meningiomas may be present. Occurrence of de novo  mutations appear in 10% of all patients with MEN1. A correlation between genotype and phenotype has not been found and, even more, combinations of these tumors may be different in members of the same family. Untreated patients have a decreased life expectancy, with a 50% probability of death by the age of 50 years and the cause of death is mostly directly related to MEN1, being the most important causes malignant pancreatic neuroendocrine tumors (NET) and thymic carcinoids. Treatment for each type of endocrine tumor is generally similar as in non-MEN1 associated tumors, but results are less successful according to multiplicity of tumors, higher metastatic disease, larger and more aggressive tumors and more resistant to treatment. The prognosis might improve by preclinical tumor diagnosis and appropriated treatment.




TÍTULO / TITLE:  - Combined Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Epidermal Growth Factor Receptor Mutation in a Female Patient Who Never Smoked.

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

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2013 Mar 22.

AUTORES / AUTHORS:  - Yoshida Y; Ota S; Murakawa T; Takai D; Nakajima J

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine.

RESUMEN / SUMMARY:  - A female patient in her sixties, who had never smoked, was found to have a 5-mm nodule in a computed tomography (CT) scan. The follow-up CT scan after 19 months  showed that the nodule had grown to 26 mm. We performed a left upper lobectomy. Pathological examination revealed a combined large cell neuroendocrine carcinoma  (LCNEC) and adenocarcinoma with components of large cell carcinoma and bronchioloalveolar carcinoma (BAC). Tumor cells were separately collected from components of both the LCNEC and adenocarcinoma, and a mutational analysis of the epidermal growth factor receptor (EGFR) gene demonstrated that both components had the same L861Q mutation at exon 21. We assume that the LCNEC originated from  the adenocarcinoma based on the fact that the patient was a non-smoking female, the tumor was located in the periphery, the tumor had a BAC component, and the same EGFR mutation was found in both the LCNEC and adenocarcinoma components.




TÍTULO / TITLE:  - Hypercalcitoninemia in thyroid conditions other than medullary thyroid carcinoma: a comparative analysis of calcium and pentagastrin stimulation of serum calcitonin.

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

REVISTA / JOURNAL:  - Langenbecks Arch Surg. 2013 Mar;398(3):403-9. doi: 10.1007/s00423-013-1049-6. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00423-013-1049-6

AUTORES / AUTHORS:  - Lorenz K; Elwerr M; Machens A; Abuazab M; Holzhausen HJ; Dralle H

INSTITUCIÓN / INSTITUTION:  - Department of General, Visceral, and Vascular Surgery, University of Halle-Wittenberg, Halle, Germany, kerstin.lorenz@uk-halle.de.

RESUMEN / SUMMARY:  - PURPOSE: Calcitonin screening aims at uncovering occult medullary thyroid cancer  (MTC) in patients with nodular thyroid disease. Elevated basal calcitonin serum levels call for calcitonin stimulation, the level of which may direct the extent  of surgery. Because pentagastrin has become restricted, calcium has increasingly  been used instead for stimulation. This study identified a new spectrum of patients demonstrating a false-positive hypercalcitoninemia in the absence of C-cell disease, carrying multinodular goiter (MNG), thyroiditis, and non-MTC thyroid malignancy, and endeavored to explore the feasibility of extrapolating pentagastrin-stimulated to calcium-stimulated calcitonin thresholds. METHODS: Altogether, 43 (9.5 %) of 455 patients with nodular thyroid disease revealed increased basal calcitonin serum levels between 2005 and 2012, for which they underwent intravenous stimulation with pentagastrin (31 patients) or calcium gluconate (12 patients) before and after primary thyroidectomy. RESULTS: Stimulation with calcium gluconate resulted in significantly higher and more variable preoperative calcitonin serum levels after 2 (241.2 vs. 104.9 pg/mL; P = 0.018) and 5 min (240.6 vs. 87.4 pg/mL; P = 0.007) than stimulation with pentagastrin. Stimulation with calcium gluconate produced 10-fold (nodular goiter), 15-fold (thyroiditis), and 21-fold (thyroid neoplasia other than MTC) calcitonin increases over baseline, as opposed to 5-fold, 10-fold, and 8-fold increases after stimulation with pentagastrin. None of the 43 patients, all of whom reverted to undetectable calcitonin serum levels after thyroide