Yoshifumi Arisaka

Balloon-occluded retrograde transvenous obliteration of high risk gastric fundal varices.

OBJECTIVE:Balloon-occluded retrograde transvenous obliteration is an effective new method for treating gastric fundal varices, but subsequent occurrence of esophageal varices creates a problem. The relationship between portal hemodynamics and the occurrence of esophageal varices after prophylactic balloon-occluded retrograde transvenous obliteration was investigated.METHODS:Ten cirrhotic patients considered to have high risk gastric fundal varices underwent angiography. Six patients showed a communication between blood flow in gastric wall vessels and that in the gastrorenal shunt (type I), whereas the others (type II) did not. Depending on the flow direction in the left gastric vein, the two groups were further divided into hepatopetal (a) and hepatofugal (b) subgroups. The therapeutic effect on portal hemodynamics and the relationship between pretreatment portal hemodynamics and posttreatment occurrence of esophageal varices were investigated.RESULTS:Fundal varices disappeared endoscopically in all 10 patients and the gastrorenal shunt was also occluded after the procedure. No patient showed worsening of liver function or systemic complications during follow-up. The increase in portal blood flow was more significant in type Ib patients than in the others. Esophageal varices occurred in all type I patients, and as to those in type Ib, high risk varices developed within 6 months after treatment. On the other hand, esophageal varices did not occur in type II patients.CONCLUSIONS:This procedure was effective for treating gastric fundal varices. However, type Ib patients are likely to develop high risk esophageal varices after occlusion of the gastrorenal shunt.

Covered self-expandable metal stents with an anti-migration system improve patency duration without increased complications compared with uncovered stents for distal biliary obstruction caused by pancreatic carcinoma: a randomized multicenter trial.

OBJECTIVES:The requirements of biliary stents used in the palliation of malignant biliary obstruction are a long duration of patency and minimal adverse effects. Covered self-expandable metal stents (SEMSs) have been shown to prevent tumor ingrowth, which is the most frequent complication of uncovered SEMSs. However, because they are prone to migration, the superiority of covered SEMS has yet to be convincingly demonstrated. The aim of this study was to evaluate the superiority of covered over uncovered SEMSs in the palliation of distal biliary obstruction due to unresectable pancreatic carcinoma, using both stent types with relatively low axial force and uncovered flared ends to prevent their migration.METHODS:From April 2009 to December 2010, 120 patients who were admitted to 22 tertiary-care centers because of distal biliary obstruction from unresectable pancreatic carcinomas were enrolled in this prospective randomized multicenter study. Patients were randomly assigned to receive a covered or uncovered SEMS deployed at the site of the biliary stricture during endoscopic retrograde cholangiopancreatography. Stent patency time, patient survival time, patient survival time without stent dysfunction (time to stent dysfunction or patient death), cause of stent dysfunction (ingrowth, overgrowth, migration, or sludge formation), and serious adverse events were compared between covered and uncovered SEMS groups.RESULTS:Patient survival time in the two groups did not significantly differ (median: 285 and 223 days, respectively; P=0.68). Patient survival time without stent dysfunction was significantly longer in the covered than in the uncovered SEMS group (median: 187 vs. 132 days; P=0.043). Stent patency was also significantly longer in the covered than in the uncovered SEMS group (mean±s.d.: 219.3±159.1 vs. 166.9±124.9 days; P=0.047). Reintervention for stent dysfunction was performed in 14 of 60 patients with covered SEMSs (23%) and in 22 of 60 patients with uncovered SEMSs (37%; P=0.08). Stent dysfunction was caused by tumor ingrowth, tumor overgrowth, and sludge formation in 0 (0%), 3 (5%), and 11 (18%) patients in the covered SEMSs group, and in 15 (25%), 2 (3%), and 6 (10%) patients in the uncovered SEMSs group, respectively. Stent migration was not observed in either group. Rates of tumor overgrowth and sludge formation did not significantly differ between the two groups, whereas the rate of tumor ingrowth was significantly lower in the covered than in the uncovered SEMS group (P<0.01). Acute pancreatitis occurred in only one patient in the covered SEMS group. Acute cholecystitis occurred in one patient in the covered SEMS group and in two patients in the uncovered SEMS group. There was no significant difference between the two groups in the incidence of serious adverse events.CONCLUSIONS:By preventing tumor ingrowth and migration, covered SEMSs with an anti-migration system had a longer duration of patency than uncovered SEMSs, which recommends their use in the palliative treatment of patients with biliary obstruction due to pancreatic carcinomas.

Results of a Japanese multicenter, randomized trial of endoscopic stenting for non-resectable pancreatic head cancer (JM-test): Covered Wallstent versus DoubleLayer stent.

Background:  No study has compared covered metallic stents with Tannenbaum stents. We evaluated the efficacy of the DoubleLayer stent (DLS) and Covered Wallstent (CWS) in patients with pancreatic head cancer (PHC).

A multicenter, prospective, randomized study of selective bile duct cannulation performed by multiple endoscopists: the BIDMEN study

BACKGROUND Wire-guided cannulation (WGC) with a sphincterotome (S) for selective bile duct cannulation (SBDC) has been reported to have a higher success rate and lower incidence of post-ERCP pancreatitis (PEP) than conventional methods in some randomized, controlled trials (RCTs) that were both single center and limited to only a few endoscopists. OBJECTIVE To estimate the difference in SBDC according to the method and catheter used in a multicenter and multiendoscopist study. DESIGN A prospective, multicenter RCT with a 2 × 2 factorial design. SETTING Fifteen referral endoscopy units. PATIENTS In total, 400 consecutive patients with naive papillae who were candidates for ERCP were enrolled and randomized. INTERVENTIONS Patients were assigned to 4 groups according to combined catheter (S or catheter [C]) and method (with/without guidewire [GW]). MAIN OUTCOME MEASUREMENTS Success rate of SBDC performed in 10 minutes, SBDC time, fluoroscopy time, and incidence of complications. RESULTS There was no significant difference in the SBDC success rate between the groups with and without GW, between C and S, or among the 4 groups (C+GW, C, S+GW, S). WGC had a tendency to significantly shorten cannulation and fluoroscopy times only in approximately 70% of patients in this study in whom SBDC was achieved in 10 minutes or less (P = .036 and .00004, respectively). All 4 groups resulted in similar outcomes in PEP (4%, 5.9%, 2%, and 2.1%, respectively). LIMITATIONS Non-double-blind study. CONCLUSIONS WGC appears to significantly shorten cannulation and fluoroscopy times. However, neither the method nor type of catheter used resulted in significant differences in either SBDC success rate or incidence of PEP in this RCT. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000002572.).

Long‐term histological prognosis and serum fibrosis markers in chronic hepatitis C patients treated with interferon

Background: Interferon (IFN) therapy is effective in 20–40% of patients with chronic hepatitis C, but the relationship between histological changes and the response to interferon is still unclear. We investigated the long‐term histological prognosis and the changes of serum fibrosis markers after interferon therapy relation to the response.

Adenocarcinoma arising in a heterotopic pancreas (Heinrich type III): a case report

IntroductionHeterotopic pancreatic cancer in the duodenum is a very rare disease. Only twelve cases have been reported worldwide to date. We report a rare case of malignant transformation of heterotopic pancreas (Heinrich type III) in the duodenum with long-term survival of the patient, and review the 12 cases in the literature.Case presentationA 75-year-old Japanese man was admitted to our hospital complaining of nausea and vomiting. Endoscopy and upper gastrointestinal contrast study showed marked duodenal stenosis. A pylorus-preserving pancreaticoduodenectomy was performed. Histopathological examination of the surgically resected specimen showed malignant transformation of heterotopic pancreas (Heinrich type III) in the duodenum. The postoperative course was uneventful, and the patient was discharged from the hospital on postoperative day 30. He is well and shows no signs of recurrence at the time of writing, six years after the surgery.ConclusionAdenocarcinoma arising within the heterotopic pancreas appears to be rare. It is difficult to obtain a correct diagnosis preoperatively. The management of heterotopic pancreas depends on the presence or absence of symptoms. If the patient is asymptomatic or benign, conservative treatment with regular follow-up is recommended. When the patient is symptomatic or there is a suspicion of malignancy, surgical management with intra-operative frozen section diagnosis is indicated.

The application of methylation specific electrophoresis (MSE) to DNA methylation analysis of the 5' CpG island of mucin in cancer cells

BackgroundMethylation of CpG sites in genomic DNA plays an important role in gene regulation and especially in gene silencing. We have reported mechanisms of epigenetic regulation for expression of mucins, which are markers of malignancy potential and early detection of human neoplasms. Epigenetic changes in promoter regions appear to be the first step in expression of mucins. Thus, detection of promoter methylation status is important for early diagnosis of cancer, monitoring of tumor behavior, and evaluating the response of tumors to targeted therapy. However, conventional analytical methods for DNA methylation require a large amount of DNA and have low sensitivity.MethodsHere, we report a modified version of the bisulfite-DGGE (denaturing gradient gel electrophoresis) using a nested PCR approach. We designated this method as methylation specific electrophoresis (MSE). The MSE method is comprised of the following steps: (a) bisulfite treatment of genomic DNA, (b) amplification of the target DNA by a nested PCR approach and (c) applying to DGGE. To examine whether the MSE method is able to analyze DNA methylation of mucin genes in various samples, we apply it to DNA obtained from state cell lines, ethanol-fixed colonic crypts and human pancreatic juices.ResultThe MSE method greatly decreases the amount of input DNA. The lower detection limit for distinguishing different methylation status is < 0.1% and the detectable minimum amount of DNA is 20 pg, which can be obtained from only a few cells. We also show that MSE can be used for analysis of challenging samples such as human isolated colonic crypts or human pancreatic juices, from which only a small amount of DNA can be extracted.ConclusionsThe MSE method can provide a qualitative information of methylated sequence profile. The MSE method allows sensitive and specific analysis of the DNA methylation pattern of almost any block of multiple CpG sites. The MSE method can be applied to analysis of DNA methylation status in many different clinical samples, and this may facilitate identification of new risk markers.

Diagnosis of Pancreatic Neoplasms Using a Novel Method of DNA Methylation Analysis of Mucin Expression in Pancreatic Juice

Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs). Our immunohistochemistry (IHC) studies have shown a consensus position on mucin expression profiles in pancreatic neoplasms as follows: MUC1-positive but MUC2-negative expression in PDACs; MUC1-negative but MUC2-positive expression in intestinal-type IPMNs (dangerous type); MUC1-negative and MUC2-negative expression in gastric-type IPMNs (safe type); High MUC4 expression in PDAC patients with a poor outcome; and MUC4-positive expression in intestinal-type IPMNs. We also showed that three mucin genes (MUC1, MUC2 and MUC4) expression in cancer cell line was regulated by DNA methylation. We have developed a novel ‘methylation-specific electrophoresis (MSE)’ method to analyze the DNA methylation status of mucin genes by high sensitivity and resolution. By using the MSE method, we evaluated pancreatic juice samples from 45 patients with various pancreatic lesions. The results were compared with final diagnosis of the pancreatic lesions including IHC of mucin expression in the paired pancreatic tissues. The results indicated that the DNA methylation status of MUC1, MUC2 and MUC4 in pancreatic juice matched with the mucin expression in tissue. Analyses of the DNA methylation status of MUC1, MUC2 and MUC4 were useful for differential diagnosis of human pancreatic neoplasms, with specificity and sensitivity of 87% and 80% for PDAC; 100% and 88% for intestinal-type IPMN; and 88% and 77% for gastric-type IPMN, respectively. In conclusion, MSE analysis of human pancreatic juice may provide useful information for selection of treatment for pancreatic neoplasms.

Smoking Status and the Incidence of Pancreatic Cancer Concomitant With Intraductal Papillary Mucinous Neoplasm.

Objectives The effect of smoking status on the incidence of pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN) has not been clarified. This study investigated the association of smoking status with PDAC concomitant with IPMN. Methods The subjects were 124 consecutive patients undergoing resection of IPMNs (intraductal papillary mucinous adenoma (IPMA): N = 77, invasive IPMN: N = 31, and PDAC with IPMN: N = 16) between April 2008 and October 2015. The associations between smoking status (never/former/current smoker) or cumulative pack-years (0–19/20–39/≥40) and the incidence of PDAC concomitant with IPMN or invasive IPMN were evaluated. Results Current smoking, not former smoking, was associated with the incidence of PDAC concomitant with IPMN (PDAC with IPMN vs IPMN alone; P = 0.004, PDAC with IPMN vs IPMA; P = 0.004, PDAC with IPMN vs invasive IPMN; P = 0.04, respectively), but not that of invasive IPMN (invasive IPMN vs IPMA; P = 0.85). Cumulative pack-years were higher in patients who had PDAC concomitant with IPMN than in patients with invasive IPMN (P = 0.04). Cumulative pack-years were not associated with smoking status (current vs former). Conclusions Current smoking, not former smoking, was associated with the incidence of PDAC concomitant with IPMN. Cessation of smoking may be recommended for patients with IPMN.

A case of lymphoepithelial cyst of pancreas with unique “cheerios-like” appearance in EUS

Lymphoepithelial cyst (LEC) of the pancreas is a rare benign lesion, which is difficult to diagnose preoperatively. We describe a case of a 60-year-old male, incidentally diagnosed as having LEC of the pancreas, which was managed by laparoscopic distal pancreatectomy. Most of the reported cases of LEC were asymptomatic and diagnosed incidentally. A high index of suspicion under EUS may help in making a diagnosis and avoiding unnecessary surgery in asymptomatic patients. In particular, the unique “cheerios-like” appearance of the lesion in EUS, which was also found in this case, might be helpful in the differential diagnosis of pancreatic cystic lesions.