Katsuyuki Miyabe

Unilateral versus bilateral endoscopic metal stenting for malignant hilar biliary obstruction.

Background and Aim:  The extent of liver drainage for palliative treatment of malignant hilar biliary obstruction is controversial. The aim of this study was to compare endoscopic unilateral versus bilateral drainage in patients with malignant hilar biliary obstruction using a self‐expanding metal stent (SEMS).

Clinical significance of extrapancreatic lesions in autoimmune pancreatitis.

Objectives: To clarify the frequency and clinical significance of extrapancreatic lesions in autoimmune pancreatitis (AIP). Methods: The frequency and clinical characteristics of extrapancreatic lesions during the clinical course of AIP were investigated retrospectively in 64 patients with AIP. The predictive factors for relapse of AIP at clinical onset were also examined. Results: Extrapancreatic lesions occurred in 95% (61/64) during the clinical course of AIP. The frequencies of sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis, and mediastinal or hilar lymphadenopathy were 84% (54/64), 23% (15/64), 16% (10/64), and 77% (27/35), respectively. Patients with sclerosing sialadenitis or extrapancreatic bile duct sclerosing cholangitis had a significantly higher serum immunoglobulin G concentration than those without (P = 0.005 and P = 0.016, respectively). Univariate analysis revealed that sclerosing sialadenitis (P = 0.005), diffuse pancreatic ductal changes (P = 0.028), and a high serum immunoglobulin G concentration (P = 0.030) at clinical onset of AIP were significant predictive factors for relapse. Multivariate analysis revealed that diffuse pancreatic ductal changes (P = 0.005) and sclerosing sialadenitis (P = 0.012) were significant independent predictive factors for relapse of AIP. Conclusions: The frequency of extrapancreatic lesions with AIP during the clinical course was high. The presence of sclerosing sialadenitis at clinical onset is a significant predictive factor for relapse of AIP.

Diagnosis of IgG4-related sclerosing cholangitis.

IgG4-related sclerosing cholangitis (IgG4-SC) is often associated with autoimmune pancreatitis. However, the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis (PSC), and the presence of segmental stenosis suggests cholangiocarcinoma (CC). IgG4-SC responds well to steroid therapy, whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention. Since IgG4-SC was first described, it has become a third distinct clinical entity of sclerosing cholangitis. The aim of this review was to introduce the diagnostic methods for IgG4-SC. IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical, serological, morphological, and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis. When intrapancreatic stenosis is detected, pancreatic cancer or CC should be ruled out. If multiple intrahepatic stenoses are evident, PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining. Associated inflammatory bowel disease is suggestive of PSC. If stenosis is demonstrated in the hepatic hilar region, CC should be discriminated by ultrasonography, intraductal ultrasonography, bile duct biopsy, and a higher cutoff serum IgG4 level of 182 mg/dL.

Predictive factors for pancreatitis and cholecystitis in endoscopic covered metal stenting for distal malignant biliary obstruction

Pancreatitis and cholecystitis are major complications after self‐expandable metal stent (SEMS) placement in distal malignant biliary obstruction. We aimed to clarify predictive factors for pancreatitis and cholecystitis after covered SEMS placement.

Comparison of intraductal ultrasonography findings between primary sclerosing cholangitis and IgG4-related sclerosing cholangitis

Comparisons of intraductal ultrasonography (IDUS) findings between primary sclerosing cholangitis (PSC) and IgG4‐related sclerosing cholangitis (IgG4‐SC) have not been elucidated. We aimed to clarify the differences in transpapillary IDUS findings between PSC and IgG4‐SC.

Clinical differences between mass-forming autoimmune pancreatitis and pancreatic cancer

Abstract Objective. Autoimmune pancreatitis (AIP) needs to be differentiated from pancreatic cancer (PC). We aimed to clarify the findings specific for AIP by comparing the clinical differences between mass-forming AIP and PC. Material and methods. We retrospectively compared 36 patients with mass-forming AIP and 60 with PC without metastasis regarding clinical, imaging, serological, histological differences and other organ involvement (OOI). We evaluated the sensitivity, specificity and accuracy of these findings for the differential diagnosis between AIP and PC. Results. The findings 100% specific for AIP were a capsule-like rim on computed tomography (CT), skipped lesion of main pancreatic duct (MPD) on endoscopic retrograde pancreatography (ERP) or magnetic resonance cholangiopancreatography (MRCP), γ-globulin > 2 g/dl, OOI (extrapancreatic biliary stricture, salivary gland swelling and retroperitoneal fibrosis) and ruling out PC by histopathological findings of endoscopic ultrasonography-guided fine-needle aspiration. The findings over 90% specific were IgG4 > 280 mg/dl (98%), IgG > 1800 mg/dl (97%), maximal diameter of upstream MPD < 5 mm on MRCP (95%) and IgG4 > 135 mg/dl (94%), respectively. Conclusions. Clinical, imaging, serological, histological findings and OOI differed between mass-forming AIP and PC. Capsule-like rim on CT, skipped lesion of MPD on ERP or MRCP, IgG4 > 280 mg/dl, and OOI were highly specific findings for AIP. These findings are useful in the differential diagnosis of mass-forming AIP from PC.

Comparative evaluation of the Japanese diagnostic criteria for autoimmune pancreatitis.

Objectives: The aim of the study was to clarify the problems of the Japanese criteria for autoimmune pancreatitis (AIP) in comparison with the other criteria. Methods: We retrospectively investigated the clinical, imaging, serological, and histopathogic features, together with other organ involvement and response to steroid, in 50 patients with AIP diagnosed on the basis of the Japanese, Korean, HISORt, and Asian criteria. Thirty-five patients with pancreatic cancer were enrolled as a control group. Results: Forty (80%) of 50 patients received a diagnosis of AIP on the basis of the Japanese criteria. Imaging findings and serological parameters fulfilled the Japanese criteria in 40 (80%) and 50 (100%) of the patients. Pathological findings fulfilled the Japanese criteria in 6 (43%) of 14 patients. All of the 10 patients who did not have a diagnosis of AIP did not fulfill the imaging criteria. Serological parameters fulfilled the Japanese criteria in 8 (23%) of 35 patients with pancreatic cancer. The sensitivities of the Japanese, Korean, HISORt, and Asian criteria for AIP were 80%, 86%, 92%, and 82%, respectively. The specificities of those 4 criteria were 89%, 89%, 97%, and 89%, respectively. Conclusions: The low sensitivity of imaging criteria and low specificity of serological criteria were the problems in the Japanese criteria.

A case of advanced-stage sclerosing cholangitis with autoimmune pancreatitis not responsive to steroid therapy.

CONTEXT Autoimmune pancreatitis and sclerosing cholangitis associated with autoimmune pancreatitis respond well to steroid therapy. Some criteria used for the differential diagnosis of autoimmune pancreatitis and sclerosing cholangitis with autoimmune pancreatitis include the response to a steroid trial. CASE REPORT A 68-year-old woman was diagnosed as having type 3 sclerosing cholangitis with autoimmune pancreatitis four years after clinical onset. Seven years after clinical onset, imaging findings revealed multiple pancreatic stones in an atrophic pancreas, stenosis of the main pancreatic duct in the head of the pancreas and upstream dilatation and a longer stretch of stenosis in the hilar hepatic region. We tried steroid therapy in an attempt to ameliorate stenosis of both the bile duct and the pancreatic duct and prevent further progression. Neither lesion responded to steroid therapy. CONCLUSION Advanced-stage sclerosing cholangitis with autoimmune pancreatitis may sometimes be unresponsive to steroid therapy, and this should be borne in mind when attempting a steroid trial for the diagnosis of sclerosing cholangitis with autoimmune pancreatitis. Early administration of steroid is important for the prevention of disease progression.

Chemopreventive effect of resveratrol and apocynin on pancreatic carcinogenesis via modulation of nuclear phosphorylated GSK3β and ERK1/2

Despite progress in clinical cancer medicine in multiple fields, the prognosis of pancreatic cancer has remained dismal. Recently, chemopreventive strategies using phytochemicals have gained considerable attention as an alternative in the management of cancer. The present study aimed to evaluate the chemopreventive effects of resveratrol (RV) and apocynin (AC) in N-Nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamster. RV- and AC-treated hamsters showed significant reduction in the incidence of pancreatic cancer with a decrease in Ki-67 labeling index in dysplastic lesions. RV and AC suppressed cell proliferation of human and hamster pancreatic cancer cells by inhibiting the G1 phase of the cell cycle with cyclin D1 downregulation and inactivation of AKT-GSK3β and ERK1/2 signaling. Further, decreased levels of GSK3βSer9 and ERK1/2 phosphorylation and cyclin D1 expression in the nuclear fraction were observed in cells treated with RV or AC. Nuclear expression of phosphorylated GSK3βSer9 was also decreased in dysplastic lesions and adenocarcinomas of hamsters treated with RV or AC in vivo. These results suggest that RV and AC reduce phosphorylated GSK3βSer9 and ERK1/2 in the nucleus, resulting in inhibition of the AKT-GSK3β and ERK1/2 signaling pathways and cell cycle arrest in vitro and in vivo. Taken together, the present study indicates that RV and AC have potential as chemopreventive agents for pancreatic cancer.

Feasibility of endoscopic retrograde cholangiopancreatography-related procedures in hemodialysis patients

The opportunities of endoscopic retrograde cholangiopancreatography (ERCP)‐related procedure for hemodialysis (HD) patients have been increasing recently. However, the complication rate of ERCPs in HD patients has not been evaluated sufficiently. We aimed to clarify the feasibility of ERCPs in HD patients.