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BackgroundThe WHO classified pancreatic neuroendocrine neoplasms in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to the Ki67 labeling index (LI). However, the clinical behavior of NEC is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs.MethodsWe retrospectively evaluated the clinicopathological characteristics, KRAS mutation status, treatment response, and the overall survival of eleven pNEC patients diagnosed between 2001 and 2014 according to the WHO 2010. We subclassified WHO-NECs into well-differentiated NEC (WDNEC) and poorly differentiated NEC (PDNEC). The latter was further subdivided into large-cell and small-cell subtypes.ResultsThe median Ki67 LI was 69.1 % (range 40–95 %). Eleven WHO-NECs were subclassified into 4 WDNECs and 7 PDNECs. The latter was further separated into 3 large-cell and 4 small-cell subtypes. Comparisons of WDNEC vs. PDNEC revealed the following traits: hypervascularity on CT, 50 % (2/4) vs. 0 % (0/7) (P = 0.109); median Ki67 LI, 46.3 % (40–53 %) vs. 85 % (54–95 %) (P = 0.001); Rb immunopositivity, 100 % (4/4) vs. 14 % (1/7) (P = 0.015); KRAS mutations, 0 % (0/4) vs. 86 % (6/7) (P = 0.015); response rates to platinum-based chemotherapy, 0 % (0/2) vs. 100 % (4/4) (P = 0.067), and median survival, 227 vs. 186 days (P = 0.227).ConclusionsThe WHO-NEC category may be composed of heterogeneous disease entities, namely WDNEC and PDNEC. These subgroups tended to exhibit differing profiles of Ki67 LI, Rb immunopositivity and KRAS mutation, and distinct response to chemotherapy. Further studies for the reevaluation of the current WHO 2010 classification are warranted.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-014-0987-2) contains supplementary material, which is available to authorized users.

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BackgroundOccult hepatitis C virus (HCV) infection (OCI) is characterized by the detection of HCV-RNA in non-serum reservoirs, such as peripheral blood mononuclear cells (PBMCs) and/or hepatocytes with undetectable HCV-RNA or antibodies in the serum. In this study, we tried to evaluate the prevalence and possible predictors of OCI in patients who achieved sustained virologic response (SVR) post sofosbuvir/daclatasvir (SOF/DCV) therapy.Patients and methodsA cross-sectional multicenter study was designed to enroll 1,280 HCV-infected patients who received SOF (400 mg) plus DCV (60 mg) once daily ± ribavirin regimen for 12 weeks and achieved SVR 12 weeks post treatment. They were randomly recruited from three dedicated Egyptian centers for management of HCV. Real-time PCR was performed to detect HCV-RNA in serum and PBMCs and to evaluate the different risk factors pertaining to the existence of OCI.ResultsHCV-RNA was detected in PBMCs of 50 (3.9%) of them. All OCI cases exhibited significant fibrosis score and raised pre-treatment alanine aminotransferase (ALT) levels. Logistic regression analysis comparing OCI with non-OCI revealed that high pre-treatment viral load, raised ALT, advanced fibrosis score, prolonged prothrombin time, low albumin, Child B score, antiviral experienced patients, and raised bilirubin are the most significant predictor for the possibility of OCI presence with Odds Ratio as 7.03, 5.13, 4.4, 2.68, 2.52, 1.9, 1.5, and 1.2, respectively.ConclusionIn spite of its remote possibility, OCI post SOF/DCV therapy may be present in some cases, and this may entail a re-auditing for the definition of SVR by dual testing in both serum and PBMCs.

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Gallbladder carcinoma sampling using ERC and EUS-FNA should be incorporated into the diagnostic workup of GB lesions as complementary tools, and EUS-FNA should be applied in the setting of failed or not indicated ERC.