Mutations in carboxy-terminal part of E2 including PKR/eIF2αphosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b:Their correlation with response to interferon monotherapy and viral load

AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR) and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-lb-infected patients treated with IFN. METHODS: The C-terminal part of E2 (codons 617-711) including PKR/eIF2a phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS: The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to IFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2 was significantly correlated with both small viral load (33.9% vs 13.8%, P = 0.0394) and sustained response to IFN (25.0% vs 6.9 %, P = 0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P < 0.0001) and sustained response to IFN (85.7% vs 2.9%, P < 0.0001). In multivariate analysis, ISDR in nonstructural (NS) 5A (OR = 0.39, P < 0.0001) and N-terminal variable region (OR = 0.51, P = 0.039) was selected as the independent predictors for small viral load, and ISDR (OR = 39.0, P < 0.0001) was selected as the only independent predictor for sustained response. CONCLUSION: The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.

Clinical oncology for pancreatic and biliary cancers:Advances and current limitations

In the early 2000s,the main stream of endoscopic ultrasonography(EUS)changed from a mechanical scanning method to electronic radial or linear scanning methods.Subsequently,useful applications in trans-abdominal ultrasonography came within reach of EUS.In particular,contrast-enhanced EUS(CE-EUS)and EUS-elastography became cutting-edge diagnostic modalities for pancreatic disorders.Each type of pancreatic disorder has characteristic hemodynamics.CE-EUS uses color Doppler flow imaging and harmonic imaging to classify pancreatic lesions.EUS-elastography can assess tissue hardness by measuring its elasticity.This parameter appears to correlate with the malignant potential of the lesions.Tissue elasticity studies can provide information on both its pattern and distribution.The former is the conventional method of morphological diagnosis,but it is restricted to observations made in a region of interest(ROI).The latter is an unbiased analysis that can be performed by image analysis software and is theoretically constant,regardless of the ROI.Though EUSfine needle aspiration(FNA)is also a very useful diagnostic tool,there are several limitations.Diagnostic EUS-FNA of pancreatic cystic lesions has marginal utility mainly due to low sensitivity.Therefore,in particular,endoscopists should keep this limitation in mind.

Pancreatolithiasis with an anatomic variant of Wirsung duct:a case report

Introduction In contrast to familiar developmental anomalies,such as pancreatobiliary maljunction and pancreas divisum,a double orifice of the ampulla of Vater is a much more rare congenital malformation.We encountered a patient with pancreatolithiasis associated with anatomic variation of Wirsung duct showing a single major duodenal papilla with a double orifice and no minor papilla.