Search

Diabetes mellitus (DM) is recognized as a risk factor for pancreatic cancer (PaC) and expected to be a clue for early diagnosis. However, it is still obscure whether a diagnostic strategy using DM as a clue can improve the prognosis or not.We retrospectively reviewed 540 patients with PaC, and investigated the prognosis with regard to the reasons for diagnosis. We compared patients diagnosed by imaging studies performed when DM was newly diagnosed or deteriorated, and patients diagnosed by symptoms.The prevalence of DM in PaC patients was 45% (256/540) and did not differ between disease stages. More than half of DM in PaC patients (150/256) were new-onset (2 years in duration). One hundred sixty one patients (30%) were asymptomatic at PaC diagnosis. There were 38 patients diagnosed in association with DM (by new-onset DM, 16; by aggravation of long-standing DM, 22). Asymptomatic patients had smaller primary tumor and were diagnosed at an earlier stage. The prognosis of PaC patients complicated with DM did not differ from that of patients without DM; however, patients had better prognosis if they were diagnosed in association with DM alone (median survival time, 20.2 months), compared with patients diagnosed by symptoms (10.2 months, P 0.01).Our analysis revealed that patients diagnosed in association with DM had better survival than symptomatic patients. Given the high prevalence of DM in PaC patients, DM can be a useful diagnostic clue for screening and lead to improvement of prognosis in PaC patients.

The long-term prognosis in patients with intraductal papillary mucinous neoplasm (IPMN) has not been determined. The aim of this study was to elucidate the risk for nonpancreatic cancer-specific mortality in patients with IPMN.Seven hundred ninety-three patients with IPMN who were followed up more than 1 year were included in this study. Fine and Gray competing risk regression was used to assess the risk for mortality unrelated to pancreatic cancer. A comorbidity score at diagnosis was assigned using the Adult Comorbidity Evaluation 27.After a median follow-up of 50 months, a high comorbidity score and age at diagnosis were significantly associated with a risk for mortality unrelated to pancreatic cancer. Adjusted hazards ratio and 95% confidence interval of each comorbidity burden were as follows: none, 1; mild, 2.68 (0.76-9.45; P = 0.124); moderate, 10.9 (3.19-37.1; P0.001); and severe, 32.0 (9.41-108.8; P0.001). Comorbidity burden did not affect the risk for pancreatic cancer-specific mortality.Comorbidity and age at diagnosis was significantly related to mortality unrelated to pancreatic cancer in patients with IPMN. For patients at high risk for nonpancreatic cancer mortality, a follow-up management may be more reasonable than surgery.

Background Feasibility of antireflux metal stent (ARMS), designed to prevent duodenobiliary reflux, was reported in patients with distal malignant biliary obstruction. In this prospective pilot study, we aimed to evaluate a newly designed ARMS as a reintervention for self-expandable metallic stent (SEMS) occlusion believed to be caused by duodenobiliary reflux. Patients and Methods Patients with non-resectable distal malignant biliary obstruction were included in whom a prior SEMS was occluded as a result of sludge or food impaction between March 2010 and January 2012 at two Japanese tertiary referral centers. The occluded SEMS were endoscopically removed, if possible, and subsequently replaced by a newly designed ARMS. We evaluated the technical success rate and complications of ARMS and compared the time to occlusion of ARMS with that of prior SEMS. Results A total of 13 patients were included. ARMS was successfully placed in all patients in a single procedure. No procedure-related complications were identified. ARMS occlusion occurred in two patients (15%), the causes of which were sludge in one patient and unknown in the other. ARMS migration occurred in four patients (31%). ARMS patency time was significantly longer than that of prior SEMS (median, not available vs 58 days; P = 0.039). Conclusions This newly designed ARMS is a technically feasible, safe, and effective reintervention for SEMS occlusion as a result of sludge or food impaction. An anti-migration mechanism to improve the outcomes of ARMS should be considered.

The aim of this study was to clarify the impact of diabetes mellitus (DM) as well as antidiabetic, antihypertensive, and antihyperlipidemic medications such as metformin and statins on survival in patients with advanced pancreatic cancer receiving chemotherapy.We retrospectively reviewed the medical records of 250 patients with advanced pancreatic cancer receiving chemotherapy. Multivariate analyses of prognostic factors for survival were performed both in overall population and in subgroups with and without DM.Diabetes mellitus was diagnosed in 124 patients (50%) who had less distant metastasis and more hypertension. Thirty patients received statin for hyperlipidemia. Overall survival was 13.3 versus 10.0 months with and without DM (P = 0.084), but hazard ratio of DM was 1.05 (P = 0.758) in the multivariate analysis. Subgroup analysis of diabetic patients, but not in non-diabetic patients, demonstrated use of statins (hazard ratio, 0.40; P = 0.010) as a prognostic factor, as well as distant metastasis, performance status, combination therapy with gemcitabine and S-1, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. No antidiabetic medications were prognostic factors.Neither DM nor antidiabetic treatment had prognostic impact on advanced pancreatic cancer. Statin use was associated with better survival in the diabetic patients.

Endoscopic placement of covered self-expandable metallic stents (CSEMSs) is effective for distal malignant biliary obstruction. However, management of dysfunctional CSEMSs has not been established. Between March 1998 and July 2007, a total of 74 patients who underwent endoscopic re-interventions for CSEMS dysfunction were analyzed. Second stent insertion (CSEMS or plastic stent) or mechanical cleaning of the occluded CSEMS was performed endoscopically. The period between second stent insertion and stent dysfunction or patient death (time to dysfunction; TTD) was calculated. The cleaned initial CSEMSs were analyzed as second stents. Dysfunction of the second stent occurred in 17 of 37 patients (45.9 %) in the CSEMS group, 16 of 20 (80.0 %) in the plastic stent group, and 13 of 17 (76.5 %) in the cleaning group. The median TTD of each group was 176, 57, and 46 days, respectively. The cumulative TTD was significantly higher in the CSEMS group than in the plastic stent and cleaning groups (P = 0.08). From the multivariate analysis, sludge occlusion of the first CSEMS was identified as a significant risk factor for second stent dysfunction (HR, 2.51; 95 % CI, 1.19–5.46), and placement of the second CSEMS significantly reduced the risk of dysfunction (HR, 0.39; 95 % CI, 0.18–0.79). Insertion of a new CSEMS should be considered as the treatment of choice for the management of dysfunctional CSEMSs.

258 Background: The data of second-line treatment for advanced biliary tract cancer is still limited. We have previously reported feasibility study of gemcitabine and cisplatin combination therapy for refractory biliary tract cancer (Sasaki T et al, Invest New Drugs 2011). In this feasibility study, only 20 pts were enrolled, and both second-line and third-line treatments were involved. Therefore, we conducted a retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment to clarify the treatment outcome of this combination therapy. Methods: Pts with advanced biliary tract cancer who were refractory to gemcitabine containing regimen were enrolled in this study. Gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2were administered intravenously on days 1 and 8 repeated every 3 weeks. Results: Fifty-nine pts were enrolled in this study. Patient characteristics were: median age 68 (range 25-84); male/female 32/27; performance status 0/1/2 (15/38/6). The primary tumor site was; 24 pts in gallbladders, 18 pts in intrahepatic bile ducts, 15 pts in extrahepatic bile ducts, and 2 pts in ampulla of Vater. The numbers of the pts with locally advanced, metastatic, and recurrent cases were 8, 44, and 7, respectively. Four pts received gemcitabine monotherapy and 55 pts received gemcitabine and S-1 combination therapy as first-line treatment. Response rate and disease control rate were 1.7% and 56.0%, respectively. The median time-to-progression and median overall survival were 3.9 months (95%CI, 2.6 – 5.0 months) and 6.4 months (95%CI, 4.9 – 8.0 months), respectively. Conclusions: Gemcitabine and cisplatin combination therapy showed a moderate efficacy for the treatment of advanced biliary tract cancer as second-line treatment.

Removal of large bile duct stones by endoscopic papillary large balloon dilation (EPLBD) with endoscopic sphincterotomy (EST) has been proven safe and effective. Little evidence supports the benefits of a preceding EST in reducing complications. Recent studies suggest that large bile duct stone removal by EPLBD alone may be safe and effective.We removed large bile duct stones by EPLBD with EST from March 2008 to February 2010 and without EST from March 2010 to October 2011. Efficacy and safety of EPLBD with or without EST and late biliary complication outcomes were assessed.Forty-two patients (men/women, 27/15; mean age, 76 years) underwent EPLBD: 14 underwent EPLBD with EST and 28 underwent EPLBD without EST. The mean stone size was 14 mm (9-30 mm). Overall complete stone removal rate was 98%, with 83% achieved in 1 session. Complete duct clearance by EPLBD alone was achieved in 79%. Mechanical lithotripsy was required in 4 (10%) patients. Extracorporeal shock wave lithotripsy and electrohydraulic lithotripsy were required in 4 (10%) and 1 (2%) patients, respectively. Pancreatitis and perforation occurred in 2 (5%) and 1 (2%) patients, respectively. Patients treated by EPLBD with EST and by EPLBD alone did not differ in complication outcomes. Six (14%) patients had recurrent bile duct stones, with a significant correlation to dilated common bile duct (p = 0.0351).EPLBD is safe and effective in patients with large bile duct stones. Preceding EST may be unnecessary.

Although the combination of biliary and duodenal self-expandable metal stents (SEMS) is useful, the exacerbating effect of duodenal SEMS placement on biliary SEMS has not been documented. We conducted a multicenter retrospective study to evaluate the effect of duodenal SEMS placement on biliary SEMS. Patients who underwent first-time biliary SEMS placement for a distal malignant biliary obstruction between September 1994 and November 2010 were included. Time to dysfunction of biliary SEMS was analyzed to identify risk factors for biliary SEMS dysfunction. Duodenal SEMS placement was analyzed as a time-dependent covariate. In total, 410 eligible patients were identified. Duodenal SEMS were placed in 33 patients (8 %). The median time to dysfunction of biliary SEMS was 170 days. Male gender (hazard ratio 1.37, 95 % confidence interval 1.03–1.83, P = 0.029) and duodenal SEMS placement (hazard ratio 2.00, 95 % confidence interval 1.16–3.45, P = 0.013) were risk factors in the multivariate Cox model. In patients undergoing duodenal SEMS, biliary SEMS dysfunction was observed in 17 (52 %) with a median time to dysfunction of 64 days after duodenal SEMS placement. As many as 60 % of the patients with biliary SEMS dysfunction after duodenal SEMS placement needed permanent percutaneous transhepatic biliary external drainage. Duodenal SEMS placement is a risk factor for biliary SEMS dysfunction. Alternative methods for biliary drainage should be considered for better biliary drainage in patients with a gastric outlet obstruction.

Background and Aim: A single-operator cholangiopancreatoscopy was developed to overcome a problem in conventional peroral cholangiopancreatoscopy. The aim of this pilot study was to clarify the clinical utility of single-operator cholangiopancreatoscopy using a SpyGlass probe through an endoscopic retrograde cholangiopancreatography (ERCP) catheter. Methods: Patients undergoing ERCP with a SpyGlass probe passed through a catheter were included in this study. The SpyGlass probe was inserted into the catheter following successful cannulation, and cholangiopancreatoscopy was performed by a single operator. We retrospectively analyzed the successful visualization rate of this technique. Results: Fifteen patients were included in this study. SpyGlass cholangiopancreatoscopy was technically successful in all patients. Successful visualization was obtained in nine patients (60%). The median SpyGlass procedure time was 10 min. Cholangiopancreatoscopic diagnoses were as follows: bile duct carcinoma in three patients; intraductal papillary mucinous adenoma in two; and intraductal pancreatic stone, benign biliary stricture, gallbladder cholesterolosis, and gallbladder carcinoma in one each. There were no cases of post-ERCP pancreatitis. Conclusions: While the low rate of successful visualization must be improved, single-operator cholangiopancreatoscopy using a SpyGlass probe through an ERCP catheter is a safe and effective procedure.

Patients with pancreatic cancer frequently suffer from both biliary and duodenal obstruction. For such patients, both biliary and duodenal self-expandable metal stent placement is necessary to palliate their symptoms, but it was difficult to cross two metal stents. Recently, endoscopic ultrasonography-guided choledochoduodenostomy (EUS-CDS) was reported to be effective for patients with an inaccessible papilla. We report two cases of pancreatic cancer with both biliary and duodenal obstructions treated successfully with simultaneous duodenal metal stent placement and EUS-CDS. The first case was a 74-year-old man with pancreatic cancer. Duodenoscopy revealed that papilla had been invaded with tumor and duodenography showed severe stenosis in the horizontal portion. After a duodenal uncovered metal stent was placed across the duodenal stricture, EUS-CDS was performed. The second case was a 63-year-old man who previously had a covered metal stent placed for malignant biliary obstruction. After removing the previously placed metal stent, EUS-CDS was performed. Then, a duodenal covered metal stent was placed across the duodenal stenosis. Both patients could tolerate a regular diet and did not suffer from stent occlusion. EUS-CDS combined with duodenal metal stent placement may be an ideal treatment strategy in patients with pancreatic cancer with both duodenal and biliary malignant obstruction.

Aim Stent migration due to peristalsis of the colon is one of the unresolved complications of colonic self-expandable metallic stent (SEMS) placement. Axial force (AF), a recovery force of the stent to a straight position after bending, has been considered a factor influencing the conformability of the digestive tract. An uncovered SEMS (Niti-S Enteral Colonic Uncovered Stent, D-type; Taewoong, Inc., Gimpo, South Korea) with improved conformability is considered to decrease migration. Methods Thirty three consecutive patients with symptomatic colorectal obstruction between March 2006 and December 2011 underwent endoscopic stent placement for palliation to estimate the efficacy and safety of Niti-S stents prospectively in four tertiary referral centers. Results Technical and clinical success rates were 100% and 97%, respectively. Seventeen patients had the following complications: ingrowth (n = 6), overgrowth (n = 1), collapse of the SEMS (n = 1), stool impaction (n = 2), migration (n = 1), bleeding (n = 3), and tenesmus (n = 3). The patient with migration had no recurrent symptoms until death. Of these 17 patients, 10 required re-interventions. Seven patients underwent an additional SEMS implantation. One patient underwent surgery for stoma creation. Two patients had stool impaction, and they underwent endoscopic cleaning. The median duration of patency was 347.0 ± 65.5 days. The mean survival time after stent insertion was 240.1 ± 39.9 days. Conclusion The new SEMS effectively relieves malignant colorectal obstruction. Good conformability, according to the very low AF, may contribute to the low incidence of migration.

Endoscopic biliary stent placement is widely accepted as palliation for malignant biliary obstruction or as a treatment of benign biliary stricture. Although various biliary stent designs have become available since self-expandable metallic stents were introduced, no single ideal stent has been developed. An ideal stent should be patent until death, or surgery, in patients with resectable malignant biliary obstruction. Fewer complications, maneuverability, cost-effectiveness, and removability are also important factors. Alternatively, should we develop a novel method for biliary drainage other than biliary stenting via endoscopic retrograde cholangiopancreatography? This article reviews the current status of biliary stenting for malignant biliary obstructions.

Aim This retrospective study estimated the efficacy and safety of the WallFlex duodenal stent for malignant gastric outlet obstruction (GOO) in Japan. Methods Forty-two consecutive patients with symptomatic malignant GOO were treated using WallFlex duodenal stents between January 2010 and October 2010. Results The technical and clinical success rates were 100% and 83.3%, respectively.The median gastric outlet obstruction scoring system increased significantly, from 0 to 2, after stent placement (P

Endoscopic papillary balloon dilation (EPBD) is a less hazardous alternative to endoscopic sphincterotomy for managing bile duct stones in patients with a coagulopathy. However, little information on EPBD is available for patients with bile duct stones who are undergoing hemodialysis (HD). We aimed to evaluate the safety and efficacy of EPBD for such patients.This was a retrospective cohort study with prospectively collected data for 37consecutive patients with bile duct stones who were undergoing HD and who also underwent EPBD between December 1995 and April 2010 at four institutions in Tokyo, Japan. The main outcome was the safety and efficacy of EPBD for managing bile duct stones in patients undergoing HD.The bile duct stones were completely removed in one session in 24 patients (64.8%). Overall success was achieved using EPBD alone in all patients. Complications occurred in five patients (13.5%), including two with hemorrhage (5.4%). No hemorrhage developed in any of the 33 patients who had no additional bleeding risk except for HD. Pancreatitis and perforation developed in two (5.4%) and one (2.7%) patient, respectively.EPBD seems to be a safe and effective treatment to extract bile duct stones in patients undergoing HD. However, EPBD should be performed carefully in patients with additional bleeding risk factors, such as Child-Pugh class C liver cirrhosis and those taking anti-platelet agents at the time of EPBD.

To determine the optimal method of endoscopic preoperative biliary drainage for malignant distal biliary obstruction.Multicenter retrospective study was conducted in patients who underwent plastic stent (PS) or nasobiliary catheter (NBC) placement for resectable malignant distal biliary obstruction followed by surgery between January 2010 and March 2012. Procedure-related adverse events, stent/catheter dysfunction (occlusion or migration of PS/NBC, development of cholangitis, or other conditions that required repeat endoscopic biliary intervention), and jaundice resolution (bilirubin level3.0 mg/dL) were evaluated. Cumulative incidence of jaundice resolution and dysfunction of PS/NBC were estimated using competing risk analysis. Patient characteristics and preoperative biliary drainage were also evaluated for association with the time to jaundice resolution and PS/NBC dysfunction using competing risk regression analysis.In total, 419 patients were included in the study (PS, 253 and NBC, 166). Primary cancers included pancreatic cancer in 194 patients (46%), bile duct cancer in 172 (41%), gallbladder cancer in three (1%), and ampullary cancer in 50 (12%). The median serum total bilirubin was 7.8 mg/dL and 324 patients (77%) had ≥ 3.0 mg/dL. During the median time to surgery of 29 d [interquartile range (IQR), 30-39 d]. PS/NBC dysfunction rate was 35% for PS and 18% for NBC [Subdistribution hazard ratio (SHR) = 4.76; 95%CI: 2.44-10.0, P0.001]; the pig-tailed tip was a risk factor for PS dysfunction. Jaundice resolution was achieved in 85% of patients and did not depend on the drainage method (PS or NBC).PS has insufficient patency for preoperative biliary drainage. Given the drawbacks of external drainage via NBC, an alternative method of internal drainage should be explored.

Aim: As for self-expandable metallic stents (SEMS) for malignant gastric outlet obstruction (GOO), some predictive factors of stent patency have been reported, although re-canalization of GOO by SEMS does not necessarily lead to favorable food intake. Therefore, we analyzed the predictive factors of oral food intake following SEMS placement. Methods: A total of 97 consecutive patients in whom SEMS were placed for malignant GOO in five hospitals were included in this retrospective study. Clinical outcomes and predictive factors influencing solid food intake were analyzed. Results: The technical and clinical success rates were 97.9% and 87.6%, respectively. The mean gastric outlet obstruction scoring system (GOOSS) improved from 0.39 to 2.24 after SEMS placement (P

Background and Aim: Wire-guided cannulation (WGC) might increase the biliary cannulation rate and decrease the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). We assessed the learning curve for WGC in therapeutic biliary ERCP (study 1) and compared WGC and conventional contrast-assisted cannulation (CC) by a matched case-control study (study 2). Methods: Prospectively collected data of 500 therapeutic biliary ERCP cases (250 consecutive cases of WGC and 250 matched controls of CC) were retrospectively studied. Rate and time of biliary cannulation, total procedure time, PEP, and hyperamylasemia were analyzed. Results: In study 1, biliary cannulation by WGC was successful in 96% of the first 50 cases, with a median time to cannulation of 3 min. Rates of hyperamylasemia were within 10% after 100 WGC. In study 2, there were no significant differences in the overall cannulation rate and PEP between WGC and CC, but the total procedure time was shorter in WGC (30 vs 35 min, P = 0.059). Rates of hyperamylasemia and the change in serum amylase levels was lower (9% vs 14%, P = 0.069, and + 62.8 U/L vs+ 169.5 U/L, P = 0.043) in WGC, which was more prominent in experienced endoscopists (9% vs 17%, P = 0.025, and + 68.9 U/L vs+ 229.3 U/L, P = 0.014). Conclusions: The introduction of WGC was effective in the first 50 cases and did not increase the rate of PEP in biliary therapeutic ERCP.

Background Although the placement of self-expandable metal stents (SEMSs) has been widely accepted as palliation for distal malignant biliary obstruction, the risk factors for their early dysfunction remain unclear. Objective To identify risk factors for early ( Design A multicenter retrospective study. Setting Five tertiary referral centers. Patients Patients were included who underwent first-time SEMS placement for distal malignant biliary obstruction caused by pancreatic cancer between April 1994 and August 2010. Main Outcome Measurements Rates and causes of early dysfunction were evaluated, and risk factors were analyzed. Results In all, 317 eligible patients were identified. Covered SEMSs were placed in 82% of patients. Duodenal invasion was observed endoscopically in 37%. The median time to dysfunction was 170 days. The rates of all and early SEMS dysfunction were 55% and 31%, respectively. The major causes of SEMS dysfunction were food impaction and nonocclusion cholangitis (21% each) in early dysfunction and sludge (29%) in nonearly dysfunction. The rate of early dysfunction was 42% with duodenal invasion and 24% without duodenal invasion ( P = .001). Early dysfunction caused by food impaction was more frequent in patients with duodenal invasion (10% and 4%, P = .053). Duodenal invasion was a risk factor (odds ratio 2.35; 95% CI, 1.43–3.90; P = .001) in a multiple logistic regression model. Limitations A retrospective design. Conclusions Duodenal invasion is a risk factor for early SEMS dysfunction in patients with pancreatic cancer.

In the endoscopic management of unresectable malignant biliary obstructions, covered metallic stents (CMSs) showed longer patency and lower incidence of stent occlusion than uncovered metallic stents (UMCs). However, there are very few reports on factors influencing the results of inserting CMSs. We evaluated differences in clinical results according to stent type.We reviewed the results of four types of CMS (polyurethane-covered Diamond stent (PCD), silicone-covered WALLSTENT (SCW), ComVi stent, and VIABIL biliary stent) and an uncovered MS (UMS), based on our experience and the literature. CMSs were characterized according to the axial and radial forces, covering (partial, full), smoothness of the inner surface, and presence of an anti-migration system.CMSs were patent significantly longer than UMSs. There were differences in stent patency among the CMSs, including the cause of occlusion and other complications. The PCD had good patency and a low incidence of migration. The ComVi stent occluded early due to food impaction, but had the longest median stent patency and a low migration rate. The incidence of migration of SCW was relatively high and the SCW was occluded primarily by sludge.We should assess the differences between the various CMSs and select the best one for each patient.

Distal malignant biliary obstruction (MBO) due to lymph node metastases (LNM) is a common problem in advanced malignant disease. However, the role of covered self-expandable metal stents (SEMS) in treating MBO has not been studied. The aim of this study was to evaluate the efficacy and safety of covered SEMS for the treatment of distal MBO due to LNM.Between November 1994 and December 2009, a total of 65 patients with distal MBO due to LNM underwent covered (n = 44) and uncovered (n = 21) SEMS placement.Successful drainage was achieved in all patients. There was no significant difference in patient survival. The cumulative stent patency of covered SEMS was significantly higher than that of uncovered SEMS (P = 0.0020). Stent occlusion occurred in 5 patients (11%) with covered SEMS and in 8 (38%) with uncovered SEMS. There was no tumor ingrowth in covered SEMS, but seven in the uncovered SEMS group showed some ingrowth. Cholecystitis was not observed, but mild pancreatitis was observed in 6 (14%) of those with covered SEMS. No stent-insertion-related deaths occurred.Covered SEMS are safe and effective for treatment of distal malignant biliary obstruction due to LNM.

Background: The renin–angiotensin system (RAS) is thought to have a role in carcinogenesis, and RAS inhibition may prevent tumour growth. Methods: We retrospectively investigated the impact of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 155 patients with pancreatic cancer receiving gemcitabine monotherapy. Patients were divided into three groups: the ACEI/ARB group (27 patients receiving an ACEI or ARB for hypertension (HT)), the non-ACEI/ARB with HT group (25 patients receiving antihypertensive drugs other than ACEIs or ARBs), and the non-HT group (103 patients receiving no antihypertensive drugs). Results: Patient characteristics were not different, except for age and HT medications. Progression-free survival (PFS) was 8.7 months in the ACEI/ARB group, 4.5 months in the non-ACEI/ARB with HT group, and 3.6 months in the non-HT group. Overall survival (OS) was 15.1 months in the ACEI/ARB group, 8.9 months in the non-ACEI/ARB with HT group, and 9.5 months in the non-HT group. The use of ACEIs/ARBs was a significant prognostic factor for both PFS (P=0.032) and OS (P=0.014) in the multivariate analysis. Conclusions: The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer. Prospective trials are needed to test this hypothesis.

Genome-wide association studies (GWASs) have identified many single nucleotide polymorphisms (SNPs) that are significantly associated with pancreatic cancer susceptibility. We sought to replicate the associations of 61 GWAS-identified SNPs at 42 loci with pancreatic cancer in Japanese and to develop a risk model for the identification of individuals at high risk for pancreatic cancer development in the general Japanese population. The model was based on data including directly determined or imputed SNP genotypes for 664 pancreatic cancer case and 664 age- and sex-matched control subjects. Stepwise logistic regression uncovered five GWAS-identified SNPs at five loci that also showed significant associations in our case-control cohort. These five SNPs were included in the risk model and also applied to calculation of the polygenic risk score (PRS). The area under the curve determined with the leave-one-out cross-validation method was 0.63 (95% confidence interval, 0.60–0.66) or 0.61 (0.58–0.64) for versions of the model that did or did not include cigarette smoking and family history of pancreatic cancer in addition to the five SNPs, respectively. Individuals in the lowest and highest quintiles for the PRS had odds ratios of 0.62 (0.42–0.91) and 1.98 (1.42–2.76), respectively, for pancreatic cancer development compared with those in the middle quintile. We have thus developed a risk model for pancreatic cancer that showed moderately good discriminatory ability with regard to differentiation of pancreatic cancer patients from control individuals. Our findings suggest the potential utility of a risk model that incorporates replicated GWAS-identified SNPs and established demographic or environmental factors for the identification of individuals at increased risk for pancreatic cancer development.

Transient elastography (with the FibroScan® apparatus) is a recently developed method for evaluating the severity of liver fibrosis by measuring liver elasticity. Liver elasticity may differ from the normal level in patients with obstructive jaundice because the retained bile may expand the liver. Because little is known about liver elasticity in patients with obstructive jaundice, we evaluated this feature in these patients. Between April 2007 and April 2008, 178 patients with biliary or pancreatic disease underwent transient elastography at the University of Tokyo Hospital. We excluded 77 patients because of concomitant cirrhotic liver disease, liver tumors, or a history of abdominal surgery. The remaining 101 patients were included in the study and were divided into obstructive jaundice (OJ; n = 43) and nonobstructive jaundice (NJ; n = 58) groups. The basic patient characteristics did not differ significantly between the two groups, except for the causative diseases. The mean liver elasticity was significantly higher in the OJ group than in the NJ group (12.0 vs. 6.2 kPa, p

Whether uni- or bilateral drainage should be performed for malignant hilar biliary obstruction remains a matter of debate. Moreover, endoscopic placement of bilateral metallic stents has been considered difficult and complicated. Although the Y-stent with a central wide-open mesh facilitates bilateral stent placement, it has limitations. This study evaluated the feasibility and efficacy of the Niti-S large cell D-type biliary stent (LCD) with a uniform large cell for both uni- and bilateral drainage of malignant hilar biliary obstruction.From April 2008 to March 2009, a total of 12 consecutive patients with unresectable malignant hilar biliary obstruction of Bismuth type 2 or greater underwent placement of LCD. Before LCD placement, all the patients underwent endoscopic unilateral biliary drainage using a plastic stent or a nasobiliary drainage tube. If jaundice improved after the procedure, the plastic stent or nasobiliary drainage tube was replaced with the unilateral LCD. If jaundice did not resolve or contralateral cholangitis occurred, bilateral LCD placement was performed.Seven patients had unilateral and five patients had bilateral LCD placement. Technical success was achieved for all 12 patients. An early complication occurred for one patient (8%), and stent occlusion occurred for six patients (50%) because of tumor ingrowth (n=4) or sludge (n=2). These patients were managed by insertion of plastic stents (n=4) or percutaneous transhepatic biliary drainage (n=2). The median stent patency period was 202 days.The newly designed endoscopic metallic stent may be feasible and effective for malignant hilar biliary obstruction, and endoscopic reintervention is relatively simple.

Background: The efficacy of double-balloon enteroscopy (DBE) for biliary interventions has been shown in patients with surgical anatomy. However, the use of available endoscopic retrograde cholangiography accessories during this procedure is limited because of the length of the conventional instrument (200 cm). The aim of this study was to evaluate the feasibility of short DBE for managing biliary disorders in patients with a Roux-en-Y gastrectomy or hepaticojejunostomy (HJ). Patients and Methods: Using a short enteroscope (152 cm) and commercially available endoscopic retrograde cholangiography accessories, biliary interventions were performed in six patients with Roux-en-Y reconstruction or HJ anastomosis. Results: A total of 12 biliary interventions were performed; balloon dilations of the HJ anastomosis or intrahepatic ducts (four patients), nasobiliary drainages (three patients), bile duct stone removal after endoscopic papillary large balloon dilation with or without small sphincterotomy (two patients), and a biliary stent placement (one patient). One patient showed retroperitoneal air following endoscopic papillary large balloon dilation, but recovered conservatively. Conclusions: Biliary interventions via DBE using a short enteroscope are feasible in patients with surgical anatomy.

Cytochrome P450 2C19 (CYP2C19) is clinically important for the metabolism of many therapeutic drugs. CYP2C19 has two main point mutation sites leading to low metabolic capacity. Several CYP enzymes are also important for the metabolism of chemical carcinogens, and several studies have reported associations between CYP polymorphism and cancer susceptibility. Speculating on a potential association between CYP2C19 polymorphism and cancer susceptibility, we conducted this study in two phases. Cell lines of various gastroenterological cancers were screened in the first phase. A clinical investigation was then conducted to confirm the association with the candidate cancer in the second phase. Genetic polymorphism of CYP2C19 was investigated in a total of 114 cell lines of five gastroenterological cancers. Based on this screening investigation suggesting an association with biliary tract cancer, we conducted a related study by recruiting 65 patients with biliary tract cancer and 566 patients with benign diseases as controls. Among the 114 cell lines investigated, biliary tract cancer was suggested to be most strongly associated with poor metabolizers of CYP2C19. Among 65 patients with biliary tract cancer, 18 (28%) were poor metabolizers of CYP2C19, whereas 87 (15%) of 566 control patients were poor metabolizers. The age- and gender-adjusted odds ratios for intermediate and poor metabolizers regarding the risk of biliary tract cancer were 1.5 (95% CI: 0.8–3.0, P = 0.17) and 2.7 (1.3–5.9, P = 0.006) compared to extensive metabolizers. A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer.

The aim of this study was to evaluate short- and long-term outcomes in relatively young patients (≤ 60 years old) who underwent endoscopic papillary balloon dilation (EPBD) for bile duct stone removal.Immediate and long-term outcomes were evaluated in 311 patients who were 60 years old or younger at the time of EPBD. The stone recurrence rate was compared among four groups stratified according to gallbladder (GB) status before and after EPBD (cholecystectomy after EPBD, GB left in situ with stones, GB left in situ without stones, and cholecystectomy before EPBD).Bile duct stones were completely removed via EPBD alone in 304 patients (97.7%). Post-EPBD pancreatitis occurred in 24 patients (7.7%), and was mild in 18 patients, moderate in 5 patients, and severe in 1 patient. The rate of pancreatitis was significantly higher in these patients than in patients aged more than 60 years who underwent EPBD during the same study period (4.7%). Long-term outcomes were evaluated in 217 patients who were followed for at least 1 year after complete stone removal via EPBD. During a mean follow-up period of 5.6 years (range, 1.0-13.4 years), stone recurrence was observed in 13 patients (6.0%). The cumulative stone recurrence rates at 5 and 10 years after EPBD were 5.9 and 7.1%, respectively. Patients in the cholecystectomy after EPBD group had the lowest risk of stone recurrence among the four groups (2.0%).EPBD removes bile duct stones in the majority of younger patients without increasing the risk of severe pancreatitis. Post-EPBD pancreatitis is more likely to occur in younger patients as compared to older patients. The long-term outcomes of EPBD appear favorable, especially in patients who have undergone cholecystectomy after EPBD.

458 Background: Both FOLFIRINOX (FFX) and Nab-paclitaxel plus Gemcitabine(GnP) standard treatment in first-line treatment of metastatic pancreatic adenocarcinoma (MPA). It could be of interest to use them consecutively, knowing that there is currently no standard for second-line treatments for MPA. The aim of this study was to compare second-line modified FFX (mFFX) after GnP failure with second-line GnP after mFFX failure. Methods: From January 2015 to Jul 2017, medical records were retrospectively reviewed for consecutive patients receiving mFFX or GnP for a histologically proven MPA after failure of GnP or mFFX respectively. Patients were treated with mFFX (intravenous oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 h, no bolus 5-FU) or GnP (Gemcitabine 1000 mg/m2/, nab-paclitaxel 125mg/m2 d1,8 15) until disease progression, patient refusal or unacceptable toxicity. Results: Second-line mFFX was administered to 50 patients and GnP was 25 patients. At baseline of second-line treatment, there was no difference in patient’s characteristics between mFFX group and GnP group. No significant difference in the response rate (mFFX, 16.6% vs. GnP, 10.5%, P = 0.63) or the disease control rate (mFFX, 50% vs. GnP, 64%, P = 0.82) was seen between the two groups. Median Progression free survival of GnP/mFFx were 4.3 months/4.6 months (p=0.89) and median survival (OS) from the 2nd line treatment of GnP/mFFx were 10.4 months/10.8 months (p=0.65) and OS from the first-line treatment of GnP/mFFx were 20.6 months/16.5 months (p=0.34). No toxic death occurred in both groups. There was no difference in the incident of adverse event between mFFX group and GnP group. Conclusions: Second-line mFFX and GnP achieved similar disease control and survival in unresectable pancreatic cancer. The use of the FFX and GnP in sequence is an attractive option to maximize disease control and survival. We need the clinical trial to compare with mFFX and GnP in sequence to guide the selection of initial chemotherapy.

Intrapancreatic bile duct stricture in autoimmune pancreatitis (AIP) is usually diagnosed as sclerosing cholangitis even if the stricture is limited to the intrapancreatic area. However, it is not known whether compression caused by pancreatic edema or biliary wall thickening causes such a biliary stricture.Our purpose was to clarify the factor that contributes to intrapancreatic biliary stricture in AIP: pancreatic head lesion or biliary wall thickening.Single-center retrospective study.This study was performed in a tertiary care academic medical center.Fifty-six patients with AIP were included.The relationship between the presence of a pancreatic head lesion and intrapancreatic biliary stricture was examined. In addition, the relationship between the extent of the intrapancreatic biliary stricture and the wall thickening was evaluated.Among 44 patients with a pancreatic head lesion, 41 (93%) had intrapancreatic bile duct stricture. Among 12 patients without a pancreatic head lesion, only 2 had such a stricture (P.0001). Intraductal US showed average intrapancreatic biliary wall thickening with severe stricture of 2.7 +/- 1.0 mm, significantly thicker than that with mild stricture (1.9 +/- 0.35 mm; P = .0200).Intraductal US was not performed in all patients.Both pancreatic edema and biliary wall thickening influenced intrapancreatic biliary stricture in AIP. This type of stricture should be differentiated from extrapancreatic biliary stricture that may be caused by biliary wall thickening only.

To evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer.Patients with a measurable lesion and no previous history of chemotherapy or radiotherapy were enrolled. Gemcitabine was administered intravenously at a dose of 1,000 mg/m(2) over 30 min on day 1 and 15, repeated every 4 weeks. S-1 was administered orally at a dose of 40 mg/m(2) b.i.d. on days 1-14. Tumor response was assessed every two cycles using Response Evaluation Criteria in Solid Tumors criteria.As much as 35 patients were enrolled between December 2006 and July 2008; 14 patients (40%) with gallbladder cancer and 14 (40%) with intrahepatic cholangiocarcinoma were included and 7 patients (20%) had received previous surgical resection. The overall response rate was 34.3% and the overall disease control rate was 82.9%. The median overall survival time was 11.6 months (95% CI, 7.3-15.6 months), and the median time to progression was 5.9 months (95% CI, 4.0-7.7 months). The grade 3/4 toxicities were leucopenia (23%), neutropenia (34%), anemia (20%), thrombocytopenia (6%) and anorexia (3%).Gemcitabine and S-1 combination chemotherapy has promising efficacy and good tolerability in patients with advanced biliary tract cancer.

Infiltration of IgG4-positive plasma cells in the pancreas and other organs is characteristic of autoimmune pancreatitis (AIP). However, it is undetermined whether needle or forceps biopsy of pancreas or other organs is indeed useful for the diagnosis of AIP. We aimed to clarify this point. Among 39 AIP patients, tissue sampling without laparotomy was performed in 27. Biopsy of pancreas, gastric mucosa, liver, bile duct, and duodenal papilla was performed in 15, 17, 11, 5 and 7, respectively. The obtained specimens were examined for IgG4-positive plasma cells. We also examined gastric mucosa of 18 patients with pancreatic cancer as controls. When the number of IgG4-positive plasma cells was more than 10 per high-power field, we regarded it as diagnostic. Diagnostic sensitivity in pancreas, gastric mucosa, liver, bile duct, and duodenal papilla was 47% (7/15), 47% (8/17), 36% (4/11), 0% (0/5), and 57% (4/7), respectively. Sensitivity of IgG4 immunostaining was unsatisfactory when tissue sampling was performed by needle or forceps biopsy. Biopsy of gastric mucosa might be a good subsidiary diagnostic tool.

Endoscopists seek to conduct more aggressive surgical procedures that surpass the limitations of existing endoscopic procedures. Endoscopic pancreatic necrosectomy and natural orifice transluminal endoscopic surgery (NOTES) are typical examples of this new trend; both are performed through the gastrointestinal wall without a skin incision. Endoscopic necrosectomy is effective for managing organized pancreatic necrosis and abscesses. The necrotic tissues are removed endoscopically by directly entering the cavity of the organized pancreatic necrosis. NOTES is a possible advance over surgical intervention, as it is a less invasive, more cosmetic, and effective procedure. There are various approaches, including the esophagus, stomach, colon, and vagina; Various procedures are possible using NOTES, such as cholecystectomy, appendectomy, full-thickness stomach resection, splenectomy, gastrointestinal (GI) anastomosis, and peritoneoscopy. The requirements for NOTES include high proficiency in endoscopic techniques, including knowledge of various devices, anatomy, and surgical procedures. Since most GI endoscopists have no surgical background, to increase the usage of NOTES, GI endoscopists should form and lead teams that include various specialists. We believe that endoscopic necrosectomy and NOTES represent a major shift in the treatment paradigm because physicians can treat beyond the gastrointestinal wall and endoscopic procedures will replace surgical treatment.

Objectives: We performed a pilot study of a modified combination chemotherapy regimen with S-1 plus gemcitabine for patients with advanced pancreatic cancer. Methods: Gemcitabine was administered at a dose of 1,000 mg/m2 in a 30-min intravenous injection on days 1 and 15. S-1 was administered orally at a dose of 40 mg/m2 twice daily for 14 consecutive days followed by a 14-day rest. Each cycle was repeated every 28 days. Results: Sixteen patients were enrolled. No complete response was observed and partial response was observed in 5 patients (31.3%), stable disease in 10 patients (62.5%) and progressive disease in 1 patient (6.3%). The median time to progression was 10.0 months (95% CI 4.4–N.A.) and the median survival time was 20.4 months (95% CI 8.6–24.1 months). The major toxicities were grade 3 neutropenia (25.0%) and grade 3 anemia (6.3%). There were no grade 4 toxicities. Conclusions: Combination therapy with gemcitabine and S-1 using the modified 4-week schedule was well tolerated and efficacious for advanced pancreatic cancer.

Background: Self-expandable metallic stents (EMSs) have been widely used for the palliative treatment of unresectable malignant biliary obstructions, but EMSs are often occluded owing to tumor ingrowth via the wire mesh. Currently, there is no consensus on the management of occluded EMSs. We evaluated the efficacy of a covered EMS as a second endoprosthesis in patients with an occluded EMS. Methods: Forty patients with an occluded uncovered EMS (14 men, 26 women; mean age 72 y, range 41 to 89 y) were studied. The patients suffered from the following: pancreatic cancer in 18, bile duct cancer in 11, gallbladder cancer in 5, lymph node metastasis in 4, and papillary cancer in 2. Of these, 26, 7, and 7 were treated with a covered EMS, an uncovered EMS, and a plastic stent (PS), respectively. The second stent was inserted as a stent-in-stent. Results: The mean patent period for the covered EMS was 220 days, whereas the mean patent periods for the uncovered EMS and plastic stent were 141 and 58 days, respectively. The cumulative patency of the covered EMS group was significantly higher (P = 0.0404) than that of the uncovered EMS group. No significant differences in survival were observed between the covered and uncovered groups. No serious complications occurred. Conclusion: Insertion of a covered EMS is an effective and safe treatment for an occluded uncovered EMS.

Objective: To chart molecular genetic events in pancreatic cancer. Methods: We analyzed genome-wide copy number alterations and loss of heterozygosity (LOH) in 25 established pancreatic cancer cell lines using a high-density single nucleotide polymorphism (SNP) array. We verified the data using genomic PCR and applied them to clinical samples. Results: Twenty-six homozygous deletion regions were detected in at least 1 cell line and LOH was found at 9p, 18q, 17p, 8p, 13q, 6q, 3p, 6p, 22q, 9q and 12q with high frequency (>50%), consistent with a previous study. Moreover, we found 23 amplified regions in at least 2 cell lines, including 8 unreported loci. We then examined representative genes at the 8 amplified loci in matched pairs of pancreatic cancer and normal tissues. The amplification was detected in 1 (7.1%) to 5 (35.7%) of 14 microdissected tissue specimens. Conclusion: Using high-resolution SNP arrays, we studied genome-wide copy number alterations and LOH simultaneously. We identified several novel and minute genomic amplifications, which contained candidate oncogenes in human pancreatic cancers.

Background: The efficacy of gemcitabine alone has not been established in comparison with conventional chemoradiotherapy for locally advanced pancreatic cancer. Methods: Of 180 consecutive patients with unresectable advanced pancreatic cancer, 93 were locally advanced. Among these 93 patients, 45 were treated with gemcitabine, 18 with concurrent radiotherapy and 5-fluorouracil-based chemotherapy, and 30 received best supportive care (BSC). In cases of metastatic disease, 42 were treated with gemcitabine and 32 received BSC. Overall survival and adverse events were analyzed retrospectively. Results: Median survival time and 1-year survival rate were 11.6, 9.3, 6.7, 7.8 and 2.4 months and 47, 39, 27, 21 and 7% in the groups of gemcitabine, chemoradiotherapy, BSC of locally advanced cancer, and in those of gemcitabine, BSC of metastatic disease, respectively. Gemcitabine and chemoradiotherapy prolonged overall survival time compared with BSC (p = 0.0071). No significant difference in survival was observed between gemcitabine and chemoradiotherapy for locally advanced cases. Adverse events >grade 3 were observed in 25 of 87 (29%) of gemcitabine-treated and in 3 of 18 (17%) of chemoradiotherapy-treated patients. Conclusion: Gemcitabine monotherapy for locally advanced pancreatic cancer could be as effective as previous chemoradiotherapy.

Acute suppurative cholangitis is fatal unless adequate biliary drainage is obtained in a timely manner. The major cause of acute suppurative cholangitis is bile duct stones, but it is not known which patients with bile duct stones are likely to develop acute suppurative cholangitis.Between May 1994 and December 2005, 343 consecutive patients with bile duct stones were referred to our department. Of these, 38 patients presented with acute suppurative cholangitis. A nasobiliary catheter or biliary stent was emergently inserted endoscopically to control acute suppurative cholangitis in those patients. Risk factors for the development of acute suppurative cholangitis in the 343 patients were investigated using univariate and multivariate analyses.A nasobiliary catheter or stent was inserted endoscopically in all 38 patients with acute suppurative cholangitis. Although biliary drainage was considered to be effective in all patients, two patients (5.3%) died of deteriorating comorbid diseases despite subsiding cholangitis. In the univariate analysis, ageor=70 years, neurological disease, and peripapillary diverticulum were identified as risk factors for the development of acute suppurative cholangitis. In the multivariate analysis, these three factors remained significant.Advanced age, comorbid neurological disease, and peripapillary diverticulum were identified as independent risk factors for the development of acute suppurative cholangitis in patients with bile duct stones.

Extracorporeal shockwave lithotripsy (ESWL) and endoscopic lithotripsy are useful for the fragmentation and extraction of pancreatic stones. However, pancreatic stones often recur, for which an adequate strategy is needed. Treatment for stricture of the main pancreatic duct (MPD) with a pancreatic stent after clearance of pancreatic stones may reduce the recurrence of pancreatic symptoms and stones.Forty patients with chronic pancreatitis with MPD stones were treated with ESWL in combination with endoscopic stone extraction. After clearance of the stones, a pancreatic stent was inserted when a stricture of MPD was observed on pancreatography. The stent was exchanged every 3 months and removed after a total of 1 year. We examined episodes of recurrent pain and pancreatitis in patients with and without stenting, as well as the MPD diameter, during follow-up.MPD stricture was seen in 27 patients, and a stent was successfully inserted in 24 of them. Pancreatic symptoms recurred in five patients (21%) in the stenting group and in three patients (23%) in the control group during a mean follow-up period of 1.5 and 1.2 years, respectively. The diameter of the MPD, before, just after, and 1 year after treatment, was 7.6, 5.4, and 5.8 mm, respectively. It was significantly decreased after 1 year of follow-up, as well as just after stent removal, compared with before treatment (P0.05).Additional stenting for MPD after extraction of pancreatic stones may reduce the risk of recurrence of pancreatic symptoms.

Among the etiologies of pyogenic liver abscess (PLA), bacterial spread from the biliary tract or portal flow is the major cause, while the onset of PLA due to arterial bacterial transmission is rare. We herein report two cases of PLA thought to be caused by arterial transmission from dental disease. In both cases, there was benign biliary stricture as a result of alcoholic chronic pancreatitis, although normal oral flora was detected as the causative bacteria and oral hygiene was poor in both patients. We presumed that the origin of PLA was dental disease and successfully treated the patients with percutaneous drainage, antibiotics and dental procedures.

A 71-year-old male who had a bile-duct cancer with liver metastases underwent systemic chemotherapy with cisplatin (25 mg/m) followed by gemcitabine (GC) (1000 mg/m). Two days after the first administration, he complained of ‘crampy’ abdominal pain. White blood cell count and levels of C-reactive protein and liver enzymes were elevated but those of creatine phosphokinase and lactate Figure 1. Japanese Journal of Clinical Oncology, 2015, 45(4) 402–403 doi: 10.1093/jjco/hyv038 Image of the Month

Background & Aims: K-ras mutation is frequently detected in pancreatic juice of patients with pancreatic small cystic lesions, as well as those with pancreatic cancer. Those cystic lesions are often found by chance with modern radiologic imaging modalities. In this study, we prospectively examined the prognosis of patients with pancreatic cystic lesions, focusing on pancreatic cancer development. Methods: A total of 197 patients with pancreatic cystic lesions, 80 with intraductal papillary mucinous neoplasm (IPMN) and 117 with non-IPMN cysts, were followed up for 3.8 years on average. Blood tests and imaging diagnosis were performed twice a year. The observed incidence of pancreatic cancer was compared with the expected incidence calculated on the basis of age- and gender-matched mortality of pancreatic cancer in the general Japanese population. Results: Pancreatic cancer developed in 7 patients during the observation period (0.95% per year), infiltrating ductal carcinoma in 5 and intraductal papillary mucinous carcinoma in 2. Three of the ductal cancer cases had pancreatic non-IPMN cyst as preexisting lesion. At least 2 of the carcinomas arose in regions remote from preexisting lesions. The observed incidence of pancreatic cancer was 22.5 times higher (95% confidence interval, 11.0–45.3) than expected mortality from this cancer among general population. Conclusions: Patients with pancreatic cystic lesions are at a considerably high risk for pancreatic cancer, with a standardized incidence rate of 22.5. Cancer might develop in regions remote from the preexisting cystic lesion, suggesting diffuse pathologic changes predisposing to malignant transformation in the entire pancreas harboring cystic lesions.

Background & Aims: Cholecystitis after metallic stent (MS) placement is an issue requiring attention. From our experience, cholecystitis seemed to occur mainly in patients with tumor involvement to the cystic duct orifice. The aim of the present study was to identify risk factors for cholecystitis in patients treated with covered or uncovered MS. Methods: We analyzed 246 patients who received MS placement (covered MS in 171 and uncovered in 75) between August 1997 and May 2005 for the treatment of unresectable distal malignant biliary obstruction. Causative diseases were as follows: pancreatic cancer in 162, papillary cancer in 10, bile duct cancer in 41, and metastatic nodes in 33 patients. Tumor involvement to orifice of the cystic duct (OCD) was diagnosed based on cholangiography and intraductal ultrasonography. Results: Cholecystitis after MS placement was found in 13 patients (5.3%). There was no significant difference in the incidence of cholecystitis between covered (5.8%) and uncovered (4.0%) MS. By univariate analysis, tumor involvement of the OCD, MS placed above the papilla, and stricture located at midportion were associated significantly with cholecystitis. By multivariate analysis, only tumor involvement of the OCD was a risk factor, with an odds ratio of 47.206 (95% confidence interval, 5.84–381.60). Conclusions: Cholecystitis after MS placement is associated with tumor involvement to the orifice of the cystic duct, regardless of the type of stent.

Autoimmune pancreatitis (AIP) has extrapancreatic complications such as Sjögren's syndrome, retroperitoneal fibrosis and sclerosing cholangitis. We studied 30 patients with AIP. Of these, we identified pulmonary involvement in four patients during follow up. Among them, two patients had respiratory failure. They showed good response to steroid therapy, but a higher dose of prednisolone was necessary to maintain remission than that required in biliary involvement. Elevation of immunoglobulin G(4) and Krebs von den Lungen-6 levels were characteristic of pulmonary involvement. They may be useful for early detection of pulmonary complication.

Objectives: New modalities, namely, endoscopic ultrasonography (EUS), magnetic resonance cholangiopancreatography (MRCP), and helical computed-tomographic cholangiography (HCT-C), have been introduced recently for the detection of common bile duct (CBD) stones and shown improved detectability compared to conventional ultrasound or computed tomography. We conducted this study to compare the diagnostic ability of EUS, MRCP, and HCT-C in patients with suspected choledocholithiasis. Methods: Twenty-eight patients clinically suspected of having CBD stones were enrolled, excluding those with cholangitis or a definite history of choledocholithiasis. Each patient underwent EUS, MRCP, and HCT-C prior to endoscopic retrograde cholangio-pancreatography (ERCP), the result of which served as the diagnostic gold standard. Results: CBD stones were detected in 24 (86%) of 28 patients by ERCP/IDUS. The sensitivity of EUS, MRCP, and HCT-C was 100%, 88%, and 88%, respectively. False negative cases for MRCP and HCT-C had a CBD stone smaller than 5 mm in diameter. No serious complications occurred while one patient complained of itching in the eyelids after the infusion of contrast agent on HCT-C. Conclusions: When examination can be scheduled, MRCP or HCT-C will be the first choice because they were less invasive than EUS. MRCP and HCT-C had similar detectability but the former may be preferable considering the possibility of allergic reaction in the latter. When MRCP is negative, EUS is recommended to check for small CBD stones.

Background & Aims: Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP), and hyperenzymemia after ERCP is common. Because ulinastatin, a protease inhibitor, has proved effective in the treatment of acute pancreatitis, the aim of this study was to assess the efficacy of ulinastatin for the prevention of post-ERCP pancreatitis and hyperenzymemia. Methods: In a multicenter, randomized, double-blind, placebo-controlled trial, patients undergoing a first ERCP were randomized to receive ulinastatin (150,000 U) or placebo by intravenous infusion for 10 minutes starting immediately before ERCP. All patients were hospitalized at least 24 hours after ERCP for evaluation of clinical symptoms. Serum pancreatic enzyme levels were measured before and at 4 and 18 hours after ERCP. The primary end point was the incidence of post-ERCP pancreatitis and the secondary objective was the occurrence of hyperenzymemia. Results: A total of 406 patients were enrolled (204 in the ulinastatin group and 202 in the placebo group). There were no differences between the 2 groups regarding baseline characteristics, details of fluoroscopic findings, or endoscopic procedure. The incidence of hyperenzymemia was significantly lower in the ulinastatin group than in the placebo group (amylase, P = .011; lipase, P = .008). Six patients in the ulinastatin group and 15 patients in the placebo group developed pancreatitis (2.9% vs. 7.4%, P = .041). There was no case of severe pancreatitis in either group. Patients who received ulinastatin did not present any side effects related to the medication. Conclusions: Prophylactic short-term administration of ulinastatin decreases the incidence of pancreatitis and hyperenzymemia after ERCP.