No abstract

Background and aim: Covered self-expandable metal stents (EMS) were recently developed to overcome tumour ingrowth in conventional EMS. However, supporting evidence for the efficacy of covered EMS is lacking. Patients and methods: We enrolled 112 patients with unresectable distal biliary malignancies. They were randomly assigned to polyurethane covered (n = 57) or original diamond stent (n = 55). Results: Stent occlusion occurred in eight patients (14%) after a mean of 304 days in the covered group, and in 21 patients (38%) after a mean of 166 days in the uncovered group. The incidence of covered EMS occlusion was significantly lower than that of uncovered EMS (p = 0.0032). The cumulative stent patency of covered stents was significantly higher than that of uncovered stents (p = 0.0066). No tumour ingrowth occurred in the covered group while it was observed in 15 patients in the uncovered group. In subgroup analysis, the cumulative patency of the covered EMS was significantly higher in pancreatic cancer (p = 0.0363) and metastatic lymph nodes (p = 0.0354). There was no significant difference in survival between the two groups. Acute cholecystitis was observed in two of the covered group and in none of the uncovered group. Mild pancreatitis occurred in five of the covered group and in one of the uncovered group. Conclusions: Covered diamond stents successfully prevented tumour ingrowth and were significantly superior to uncovered stents for the treatment of patients with distal malignant biliary obstruction. However, careful attention must be paid to complications specific to covered self-expandable metal stents, such as acute cholecystitis and pancreatitis.

No abstract

Objectives: Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis, and has a favourable response to corticosteroid treatment (CST). Little is known, however, about the long-term outcome of AIP. This study aimed to document the prognosis without and with CST, and to examine the indication for CST. Patients and methods: The prognosis and clinical features of 23 patients without CST and 19 patients treated with CST from onset were investigated. In addition, factors concerning the late occurrence of unfavourable events related to AIP were examined. Results: The patients without CST were 19 men and four women, with an average age of 66 years. After an average observation period of 25 months, 16 patients (70%) developed unfavourable events including obstructive jaundice as a result of distal bile duct stenosis in four, growing pseudocyst in one, sclerogenic changes of extrapancreatic bile duct in nine, hydronephrosis as a result of retroperitoneal fibrosis in one, and interstitial nephritis in one. Patients with obstructive jaundice at onset showed a higher cumulative event occurrence rate (p = 0.025). The patients treated with CST were 16 men and three women, with an average age of 64 years. After an average observation period of 23 months, six patients (32%) developed unfavourable events consisting of interstitial pneumonia in three, and a recurrence of obstructive jaundice in three. In multivariate analysis, CST (HR 0.33, 95% CI 0.12-0.89, p = 0.029) and obstructive jaundice at onset (HR 3.09, 95% CI 1.14-8.32, p = 0.026) were significant predictive factors for unfavourable events. Conclusion: CST could reduce AIP-related unfavourable events. The early introduction of CST is recommended especially for patients with obstructive jaundice.

Purpose: To investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for prediction of tumor differentiation, P-glycoprotein (P-gp) expression, and outcome in hepatocellular carcinoma (HCC) patients. Experimental Design: Seventy HCC patients who underwent curative resection were prospectively enrolled in the study. FDG-PET was done 2 weeks preoperatively, and the standardized uptake value (SUV) and the tumor to nontumor SUV ratio (TNR) were calculated from FDG uptake. Tumor differentiation and P-gp expression were examined with H&E and immunohistochemical staining, respectively. Results: SUV and TNR were significantly higher in poorly differentiated HCCs than in welldifferentiated (P = 0.001 and 0.002) and moderately differentiated HCCs (P < 0.0001 and P < 0.0001). The percentage P-gp^positive area was significantly higher in well-differentiated HCCs than in poorly differentiated (P < 0.0001) and moderately differentiated HCCs (P = 0.0001). Inverse correlations were found between SUV and P-gp expression (r = À0.44; P < 0.0001) and between TNR and P-gp expression (r = À0.47; P = 0.01). Forty-three (61.4%) patients had postoperative recurrence. The overall and disease-free survival rates in the highTNR (z2.0) group were significantly lower than in the lowTNR (<2.0) group (P = 0.0001and 0.0002). In multivariate analysis, a high a-fetoprotein level (risk ratio, 5.46; P = 0.003; risk ratio, 8.78; P = 0.006) and high TNR (risk ratio, 1.3; P = 0.03; risk ratio, 1.6; P = 0.02) were independent predictors of postoperative recurrence and overall survival. Conclusions: The results suggest that preoperative FDG-PET reflects tumor differentiation and P-gp expression and may be a good predictor of outcome in HCC.

CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) is a key component in endoplasmic reticulum (ER) stress-mediated apoptosis. The goal of the study was to investigate the role of CHOP in cholestatic liver injury. Acute liver injury and liver fibrosis were assessed in wild-type (WT) and CHOP-deficient mice following bile duct ligation (BDL). In WT livers, BDL induced overexpression of CHOP and Bax, a downstream target in the CHOP-mediated ER stress pathway. Liver fibrosis was attenuated in CHOP-knockout mice. Expression levels of α-smooth muscle actin and transforming growth factor-β1 were reduced, and apoptotic and necrotic hepatocyte death were both attenuated in CHOP-deficient mice. Hepatocytes were isolated from WT and CHOP-deficient mice and treated with 400 μM glycochenodeoxycholic acid (GCDCA) for 8 h to examine bile acid-induced apoptosis and necrosis. GCDCA induced overexpression of CHOP and Bax in isolated WT hepatocytes, whereas CHOP-deficient hepatocytes had reduced cleaved caspase-3 expression and a lower propidium iodide index after GCDCA treatment. In conclusion, cholestasis induces CHOP-mediated ER stress and triggers hepatocyte cell death, and CHOP deficiency attenuates this cell death and subsequent liver fibrosis. The results demonstrate an essential role of CHOP in development of liver fibrosis due to cholestatic liver damage.

BACKGROUND & AIMS: Long-term outcomes of patients with branch-duct intraductal papillary mucinous neoplasms (IPMNs), particularly those after 5 years of surveillance, have not been fully evaluated in large studies. We analyzed incidences of IPMN-derived carcinoma and concomitant ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]) over 20 years in a large population of patients. METHODS: We identified 1404 consecutive patients (52% women; mean age, 67.5 years) with a diagnosis of branch-duct IPMN, from 1994 through 2017, at the University of Tokyo in Japan. Using a competing risk analysis, we estimated cumulative incidence of pancreatic carcinoma, overall and by carcinoma type. We used competing risks proportional hazards models to estimate subdistribution hazard ratios (SHRs) for incidences of carcinomas. To differentiate IPMN-derived and concomitant carcinomas, we collected genomic DNA from available paired samples of IPMNs and carcinomas and detected mutations in GNAS and KRAS by polymerase chain reaction and pyrosequencing. RESULTS: During 9231 personyears of follow-up, we identified 68 patients with pancreatic carcinomas (38 patients with IPMN-derived carcinomas and 30 patients with concomitant PDACs); the overall incidence rates were 3.3%, 6.6%, and 15.0% at 5, 10, and 15 years, respectively. Among 804 patients followed more than 5 years, overall cumulative incidence rates of pancreatic carcinoma were 3.5% at 10 years and 12.0% at 15 years from the initial diagnosis. The size of the IPMN and the diameter of the main pancreatic duct associated with incidence of IPMNderived carcinoma (SHR 1.85; 95% confidence interval 1.38-2.48 for a 10-mm increase in the IPMN size and SHR 1.56; 95% confidence interval 1.33-1.83 for a 1-mm increase in the main pancreatic duct diameter) but not with incidence of concomitant PDAC. CONCLUSIONS: In a large long-term study of patients with branch-duct IPMNs, we found the 5year incidence rate of pancreatic malignancy to be 3.3%, reaching 15.0% at 15 years after IPMN diagnosis. We observed heterogeneous risk factor profiles between IPMNderived and concomitant carcinomas.

No abstract