Tomoaki Ando

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.

Usefulness of transpapillary bile duct brushing cytology and forceps biopsy for improved diagnosis in patients with biliary strictures

Background and Aim:  Transpapillary bile duct brushing cytology and/or forceps biopsy was performed in the presence of an indwelling guidewire in patients with biliary stricture, and the treatment time, overall diagnosis rate, diagnosis rate of each disease, complications, and influences on subsequent biliary drainage were investigated.

Diagnostic procedures for IgG4-related sclerosing cholangitis

Background/purposeIgG4-related sclerosing cholangitis (IgG4-SC) is one of several diseases associated with autoimmune pancreatitis (AIP). However, diffuse cholangraphic abnormalities seen in association with AIP may resemble those seen in primary sclerosing cholangitis (PSC), and the presence of segmental stenosis suggests cholangiocarcinoma. IgG4-SC responds well to steroid therapy, whereas in contrast, liver transplantation is the only effective therapy for PSC, and surgical intervention is also needed for cholangiocarcinoma. The aim of this review was to establish the diagnostic procedures for IgG4-SC.MethodsA literature search was conducted, covering English-language articles dealing with IgG4-SC published between 1991 and March 2010. As clinical data on IgG4-SC are limited, the author also took into consideration his own clinical experience with the treatment of IgG4-SC over a period of more than 19 years.ResultsWhen intrapancreatic stenosis is detected, pancreatic cancer should be ruled out. If multiple intrahepatic stenosis is evident, PSC should be discriminated on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining. An association with inflammatory bowel disease (IBD) is suggestive of PSC. If stenosis is demonstrated in the hepatic hilar region, cholangiocarcinoma should be discriminated by US, EUS, IDUS, and bile duct biopsy.ConclusionFor diagnosis of IgG4-SC, coexistence of AIP is the most useful finding. However, the most important consideration for clinicians is to be aware of IgG4-SC when encountering patients with obstructive jaundice.

Blockage of angiotensin II type 1 receptor regulates TNF-α-induced MAdCAM-1 expression via inhibition of NF-κB translocation to the nucleus and ameliorates colitis

Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is an important target in the treatment of inflammatory bowel disease (IBD). Recently, treatment of IBD with an antibody to alpha4beta7-integrin, a ligand for MAdCAM-1, has been an intense focus of research. Our aim was to clarify the mechanism by which MAdCAM-1 is regulated via angiotensin II type 1 receptor (AT1R), and to verify if AT1R might be a novel target for IBD treatment. The role of AT1R in the expression of MAdCAM-1 in SVEC (a murine high endothelial venule cell) and MJC-1 (a mouse colonic endothelial cell) was examined following cytokine stimulation. We further evaluated the effect of AT1R on the pathogenesis of immune-mediated colitis using AT1R-deficient (AT1R-/-) mice and a selective AT1R blocker. AT1R blocker significantly suppressed MAdCAM-1 expression induced by TNF-alpha, but did not inhibit phosphorylation of p38 MAPK or of IkappaB that modulate MAdCAM-1 expression. However, NF-kappaB translocation into the nucleus was inhibited by these treatments. In a murine colitis model induced by dextran sulfate sodium, the degree of colitis, judged by body weight loss, histological damage, and the disease activity index, was much milder in AT1R-/- than in wild-type mice. The expression of MAdCAM-1 was also significantly lower in AT1R-/- than in wild-type mice. These results suggest that AT1R regulates the expression of MAdCAM-1 under colonic inflammatory conditions through regulation of the translocation of NF-kappaB into the nucleus. Furthermore, inhibition of AT1R ameliorates colitis in a mouse colitis model. Therefore, AT1R might be one of new therapeutic target of IBD via regulation of MAdCAM-1.

IgG4-related hepatic inflammatory pseudotumor with sclerosing cholangitis: a case report and review of the literature

IntroductionInflammatory pseudotumor is rare benign mass composed of chronic inflammatory cell infiltration and proliferating fibrous tissue. Some cases of inflammatory pseudotumor show abundant infiltrating IgG4-positive plasma cells and obliterative phlebitis, which are the pathologic hallmarks of autoimmune pancreatitis.Case presentationA 77-year-old Japanese man was admitted to our hospital because of epigastric pain. A solitary mass with delayed enhancement by dynamic computed tomography was present in the left hepatic lobe. Endoscopic retrograde cholangiography showed only segmental stenosis of the left intrahepatic bile duct. No abnormal findings were detected in the pancreas. The patient was clinically diagnosed as having intrahepatic cholangiocarcinoma and underwent surgery. Histological examination of the hepatic mass and bile duct wall showed abundant IgG4-positive plasma cell infiltration with obliterative phlebitis. The final diagnosis was IgG4-related hepatic inflammatory pseudotumor with sclerosing cholangitis. Delayed enhancement by computed tomography is a characteristic feature of IgG4-related inflammatory pseudotumor similar to that of autoimmune pancreatitis.ConclusionIgG4-related hepatic inflammatory pseudotumor unassociated with autoimmune pancreatitis should be one of the entities considered for differential diagnosis of liver tumors. Delayed enhancement on computed tomography might be useful finding for diagnosing IgG4-related hepatic inflammatory pseudotumor.

Gastroesophageal and laryngopharyngeal reflux symptoms correlate with histopathologic inflammation of the upper and lower esophagus.

Background The presence of laryngopharyngeal reflux disease is controversial when abnormal sensation of the laryngopharynx is felt without heartburn. Goals The aims of this study were to investigate the relationship between abnormal sensation of the laryngopharynx and gastroesophageal reflux, and to elucidate the pathology of laryngopharyngeal reflux disease by investigating histopathologic findings of the upper and lower esophagus. Study Upper and lower esophageal tissues were biopsied by endoscopy in 300 consenting patients, excluding those with serious diseases. Results Fifty-seven patients (19.0%) reported reflux symptoms alone (reflux symptom group), 48 patients (16.0%) reported abnormal sensation of the laryngopharynx alone (abnormal laryngopharyngeal sensation group), and 74 patients (24.7%) reported both reflux symptoms and abnormal sensation of the laryngopharynx (complication group), whereas 121 patients (40.3%) did not report subjective reflux symptoms and abnormal sensation of the laryngopharynx (control group). Histopathologic inflammation of the upper esophagus was significantly greater in the complication and abnormal laryngopharyngeal sensation groups compared with the control group. Histologic inflammation of the lower esophagus was significantly higher in the complication and reflux symptom groups compared with the control group. Conclusions The histopathologic findings of the upper and lower esophagus elucidated an association between gastroesophageal reflux and abnormal sensation of the laryngopharynx.

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.

Hemosuccus Pancreaticus Associated with Segmental Arterial Mediolysis Successfully Treated by Transarterial Embolization

CONTEXT Hemosuccus pancreaticus, a rare cause of intermittent upper gastrointestinal bleeding, is usually caused by the rupture of an aneurysm associated with chronic pancreatitis. Segmental arterial mediolysis is a rare non-arteriosclerotic, non-inflammatory vascular disease characterized by vacuolization and lysis of the arterial smooth muscle cells. Segmental arterial mediolysis often causes intra-abdominal hemorrhage through aneurysm rupture. To our knowledge, hemosuccus pancreaticus associated with segmental arterial mediolysis has not previously been reported. CASE REPORT A 59-year-old man had suffered from recurrent episodes of epigastric pain and melena. Laboratory data showed mild anemia and an elevated serum amylase level. Upper gastrointestinal endoscopy revealed bloody pancreatic juice exuding from the papilla of Vater. There were no findings suggestive of chronic pancreatitis, such as pancreatic calcification, irregularity of the pancreatic duct and atrophy of the pancreas. Contrast-enhanced computed tomography revealed a large fusiform aneurysm of the middle-distal splenic artery, and dissection of the proximal splenic artery and celiac artery. Leakage of contrast medium from the aneurysm into the main pancreatic duct was also evident. Angiography clearly revealed a fusiform aneurysm of the splenic artery. This was managed successfully by transarterial coil embolization and the patient has subsequently shown no recurrence of epigastric pain or melena. CONCLUSION Segmental arterial mediolysis is a very rare cause of hemosuccus pancreaticus not associated with chronic pancreatitis. Transcatheter arterial embolization is useful for treatment of ruptured aneurysm associated with segmental arterial mediolysis.