Kazumichi Kawakubo

Multicenter retrospective study of endoscopic ultrasound-guided biliary drainage for malignant biliary obstruction in Japan

Endoscopic ultrasound‐guided biliary drainage (EUS‐BD) is considered to be an effective salvage procedure for failed endoscopic retrograde cholangiopancreatography in patients with unresectable malignant biliary obstruction. The aim of this retrospective study was to evaluate the efficacy and feasibility of EUS‐BD.

Incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasms of the pancreas

Background and aims Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been reported to be associated with extrapancreatic malignancies, but there have been no prospective studies evaluating the incidence of extrapancreatic cancers in patients with IPMNs. In this study, the frequency of patients with IPMNs developing extrapancreatic cancers during follow-up was examined. Methods 642 patients with IPMNs were prospectively followed up for 4.8 years on average. They underwent clinical examination at least twice a year. The incidence of the observed extrapancreatic malignancies was compared with the expected incidence of the age- and gender-matched general Japanese population based on the Vital Statistics of Japan. Results 40 extrapancreatic cancers developed in 39 patients during follow-up (1.3% per year). The most common malignancies were hepatocellular (n=7), colorectal (n=6), gastric (n=6), lung (n=5) and prostate cancers (n=4). The calculated standardised incidence rate of each of the malignancies was not significant, as follows: hepatocellular 2.17 (95% CI 0.87 to 4.47), colorectal 1.02 (0.37 to 2.21), gastric 0.76 (0.28 to 1.66), lung 0.75 (0.24 to 1.76) and prostate 1.00 (0.71 to 1.29). Pancreatic cancer was observed in 17 patients during the same period, with a standardised incidence rate of 10.7 (6.2 to 17.1). Conclusions The incidence of extrapancreatic malignancies in patients with IPMNs was similar to that in the general population, whereas the incidence of pancreatic cancers was significantly high. Intraductal papillary mucinous neoplasms are not associated with systemic carcinogenesis except for pancreatic cancer.

Management of malignant gastric outlet obstruction with a modified triple-layer covered metal stent

BACKGROUND A high incidence of migration with covered metal stents has been reported in malignant gastric outlet obstruction (GOO). A newly modified, partially covered, triple-layer nitinol stent was developed that has a longer uncovered portion (5-15 mm) to prevent stent migration. OBJECTIVE To estimate the efficacy and safety of the modified covered, triple-layer metal stent. DESIGN Multicenter, prospective cohort study. SETTING Three tertiary referral centers. PATIENTS Fifty consecutive patients (26 with pancreatic carcinoma, 14 with gastric carcinoma, 9 with cholangiocarcinoma, 1 with a metastatic node) who presented with symptomatic unresectable malignant GOO between April 2007 and March 2010. INTERVENTIONS Endoscopic placement of the modified covered, triple-layer metal stent. MAIN OUTCOME MEASUREMENTS The primary endpoint was to improve the GOO scoring system (GOOSS) score. Secondary endpoints were success rate, patency, and complications. RESULTS The median GOOSS score improved significantly (P < .0001) after stenting (from 0 to 3). The technical and clinical success rates were 100% and 90%, respectively. Stent occlusion by tumor overgrowth or ingrowth at the uncovered portion developed in 5 patients (10%). Asymptomatic stent migration occurred in 3 patients (6%) receiving chemotherapy at 95, 230, and 553 days after stent placement, but these patients tolerated solid food 68, 260, and 142 days after stent migration, respectively. Other complications occurred in 1 patient with insufficient expansion, cholangitis, and pancreatitis. No procedure-related deaths occurred. LIMITATIONS A single-arm study in tertiary-care centers. CONCLUSIONS The modified covered, triple-layer metal stent was effective and safe for managing malignant GOO and can prevent tumor ingrowth and stent migration. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000004566.).

Japanese multicenter estimation of wallflex duodenal stent for unresectable malignant gastric outlet obstruction

This retrospective study estimated the efficacy and safety of the WallFlex duodenal stent for malignant gastric outlet obstruction (GOO) in Japan.

Duodenal invasion is a risk factor for the early dysfunction of biliary metal stents in unresectable pancreatic cancer.

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 (<3 months) SEMS dysfunction in unresectable pancreatic cancer. 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.

Clinical Outcomes of Chemotherapy for Diabetic and Nondiabetic Patients With Pancreatic Cancer: Better Prognosis With Statin Use in Diabetic Patients.

Objectives 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. Methods 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. Results 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. Conclusions Neither DM nor antidiabetic treatment had prognostic impact on advanced pancreatic cancer. Statin use was associated with better survival in the diabetic patients.

Predictive factors of solid food intake in patients with malignant gastric outlet obstruction receiving self‐expandable metallic stents for palliation

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.

Impact of S-1 on the survival of patients with advanced pancreatic cancer.

Objective: The aim of this study was to investigate the effect of S-1 on the prognosis of advanced pancreatic cancer. Methods: In total, 112 patients with pancreatic cancer who received chemotherapy between April 2001 and April 2007 were divided into 2 groups: PreS-1 (53 patients who started chemotherapy before January 2005) and PostS-1 (59 patients who started chemotherapy after February 2005, the time of S-1 introduction). Patient characteristics and clinical outcomes were compared, and prognostic factors were analyzed. Results: Patient characteristics did not significantly differ between the 2 groups. S-1 was administered as a second-line monotherapy in 5.7% of the PreS-1 group and combined with gemcitabine as a first-line therapy in 27.1% or as second-line monotherapy in 23.7% in the PostS-1 group. Both progression-free survival and overall survival improved after introduction of S-1 (median progression-free survival, 4.4 and 5.3 months; P = 0.043; median overall survival, 9.5 and 13.1 months; P = 0.048 in PreS-1 and PostS-1 groups, respectively). Multivariate analysis revealed that the PostS-1 group (hazards ratio, 0.52; P = 0.003), performance status, and carcinoembryonic antigen were significant prognostic factors for survival. Conclusions: Introduction of S-1 may improve the prognosis of Japanese patients with advanced pancreatic cancer.

Short- and long-term outcomes of endoscopic papillary large balloon dilation with or without sphincterotomy for removal of large bile duct stones.

Abstract Objective. 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. Material and methods. 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. Results. 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). Conclusions. EPLBD is safe and effective in patients with large bile duct stones. Preceding EST may be unnecessary.

Clinical significance of bile cytology via an endoscopic nasobiliary drainage tube for pathological diagnosis of malignant biliary strictures

Background/purposeIn patients in whom there is a suspicion of malignant biliary strictures, bile cytology via an endoscopic nasobiliary drainage tube (ENBD cytology) is often performed, in addition to aspirated bile cytology, brush cytology, and forceps biopsy, during the initial endoscopic retrograde cholangiopancreatography (ERCP). We aimed to reveal the significance of ENBD cytology for the pathological diagnosis of malignant biliary strictures.MethodsWe studied 214 patients with malignant biliary strictures. We performed aspirated bile cytology, brush cytology, and forceps biopsy in 93, 130, and 114 patients, respectively. ENBD cytology was performed one or more times in 79 patients. We examined the sensitivity of each sampling method, and analyzed the utility of ENBD cytology.ResultsThe sensitivities of each sample acquisition method were as follows: 30% (28/93) for aspirated bile cytology, 48% (62/130) for brush cytology, 41% (47/114) for forceps biopsy, and 24% (19/79) for ENBD cytology. In 19 patients who showed positive ENBD cytology, other methods were performed in 11. Aspirated bile cytology, brush cytology, and forceps biopsy, were performed in 7, 5, and 6 patients, and the results were negative in 3 (43%), 2 (40%), and 1 (17%) patient, respectively. Three patients showed positive results only on ENBD cytology.ConclusionsAlthough the sensitivity of ENBD cytology was inferior to that of the other methods used, ENBD cytology may contribute to the improvement of the total diagnostic sensitivity for malignancy.