Utility of single and double balloon endoscopy in patients with difficult colonoscopy: a randomized controlled trial.

AIM: To compare the utility of single-balloon colonoscopy (SBC) or double-balloon colonoscopy (DBC) for difficult colonoscopies. METHODS: Between August 2008 and June 2010, patients in whom total colonoscopy failed within 30 min of insertion were assigned randomly to undergo either SBC or DBC. No sedatives were used. After the endoscopy, all patients were asked to evaluate pain during the procedure on a 10-point analog scale (1 = no pain; 10 = worst imaginable pain) with a questionnaire. The study outcomes were the cecal intubation rate and time, endoscopic findings, complications, and pain score. RESULTS: The SBC and DBC groups included 11 and 10 patients, respectively. All but one SBC patient achieved total colonoscopy successfully. The cecal intubation times were 18 min (range: 10-85 min) and 12.8 min (range: 9.5-42 min) in the SBC and DBC groups, respectively (P = 0.17). No difference was observed in the prevalence of colon polyps between the SBC and DBC groups (45% vs 30%, P = 0.66). SBC showed advanced colon cancer in the ascending colon, which was inaccessible using conventional colonoscopy. The respective pain scores were 5 (1-10) [median (range)] and 5 (1-6) in the SBC and DBC groups (P = 0.64). No complications were noted in any patient. CONCLUSION: The utility of single- and double-balloon endoscopy for colonoscopy seems comparable in patients with incomplete colonoscopy using a conventional colonoscope.

Incidental pancreatic cysts found by magnetic resonance imaging and their relationship with pancreatic cancer.

OBJECTIVES: We examined whether the presence of pancreatic cysts could be a risk for pancreatic cancer by comparing the incidence and characteristics of cysts found by magnetic resonance (MR) imaging in patients with and without pancreatic cancer. METHODS: Half-Fourier rapid acquisition with relaxation enhancement images and MR cholangiopancreatography were performed in 116 patients with pancreatic cancer (PC group) and 1226 with nonpancreatic disease (NP group). Incidence and characteristics of cysts were analyzed. RESULTS: Pancreatic cysts were detected in 65 patients (56%) of the PC group and in 123 patients (10%) of the NP group. According to the multivariate analysis, cyst presence was a significant risk factor for pancreatic cancer (odds ratio [OR], 10.27; P < 0.01), especially cysts larger than 10 mm (OR, 4.718; P < 0.01). When the definition of cyst presence in the PC group was restricted to the 33 cases with cysts considered to have existed before the development of cancer, the incidence was still high (OR, 2.976; P < 0.01) and size remained significant (OR, 4.428; P < 0.01). CONCLUSIONS: Patients with pancreatic cysts, especially larger than 10 mm, were considered to be at an increased risk of pancreatic cancer over the entire pancreas.

Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In this study we examined the differences in genetic alteration(s) among the IPMN subtypes. METHODS: Surgically resected IPMNs (n = 25) were classified into four subtypes by hematoxylin and eosin (H&E) and mucin immunostaining. Mutations in KRAS, BRAF, and PIK3CA genes and expression of CDKN2A, TP53, SMAD4, phospho-ERK, and phospho-SMAD1/5/8 proteins were examined. RESULTS: There were 11 gastric, 11 intestinal, one pancreatobiliary, and two oncocytic types in this study. We then compared the two major subtypes, gastric-type and intestinal-type IPMN. Gastric-type IPMN showed a significantly higher incidence of KRAS mutations (9/11, 81.8%) compared with intestinal type (3/11, 27.3%; p < 0.05), although the intestinal type showed a higher grade of dysplasia than gastric type (p < 0.01). All cases with KRAS mutations showed phospho-ERK immunostaining. In contrast, intestinal type (9/11, 81.8%) showed more frequent SMAD1/5/8 phosphorylation compared with gastric-type IPMN (3/11, 27.3%; p < 0.05%). CONCLUSIONS: There may be distinct mechanisms of pancreatic cancer progression in the different subtypes of IPMN. In particular, KRAS mutation and bone morphogenetic protein-SMAD signaling status may be crucial diverging steps for the two representative pathways to pancreatic cancer in IPMN patients.

Endoscopic submucosal dissection is an effective and safe therapy for early gastric neoplasms: a multicenter feasible study.

BACKGROUND AND AIM: The technique of endoscopic submucosal dissection (ESD) was introduced to obtain en bloc specimens of large early gastrointestinal neoplasms. The drawback of ESD is its technical difficulty and, consequently, its higher rate of complication. In this multicenter study, we investigated the therapeutic outcomes of ESD in consecutive patients. METHODS: From January 2002 to December 2008, 485 early gastric neoplasms in 418 patients were consecutively treated by using ESD procedure performed by 6 endoscopists in 4 institutions in Tokyo. Demorgraphics, tumor location, therapeutic outcomes, and complication rates were analyzed. RESULTS: The rates of en bloc resection, complete en bloc resection, submucosal invasion, and piecemeal resection were 93.6%, 85.4%, 10.9%, and 5.4%, respectively. In multivariate analysis, the en bloc resection rate was independently lower in lesions in upper portion than in lower portion (P<0.01), lower in larger lesions (>30 mm, P<0.05; 20 to 30 mm, P<0.05), and lower in lesions with a scar (P<0.01). Delayed bleeding occurrence was independently high in larger lesions (>30 mm, P<0.01; 20 to 29 mm, P<0.01) than in small lesions (<20 mm). Institution and endoscopists were not risk factors of en bloc resection and complications CONCLUSIONS: ESD is an effective and safe therapy in the management of early gastric neoplasms when performed by well-trained endoscopists. Endoscopists should recognize the difficulty to perform ESD for en bloc resection of upper lesion, and the risk of delayed bleeding in cases of lesions >2 cm in size.

Fever-based antibiotic therapy for acute cholangitis following successful endoscopic biliary drainage.

BACKGROUND: The current management of acute cholangitis consists of antibiotic therapy in combination with biliary drainage. However, the optimal duration of antibiotic therapy after the resolution of clinical symptoms by biliary drainage is unclear. We aimed to evaluate whether discontinuing antibiotic therapy for acute cholangitis immediately after the resolution of clinical symptoms, achieved by endoscopic biliary drainage, was safe and effective. METHODS: This prospective study included patients with moderate and severe acute cholangitis. Cefmetazole sodium and meropenem hydrate were used as initial antibiotic therapy for patients with moderate and severe acute cholangitis, respectively. All patients underwent endoscopic biliary drainage within 24 h of diagnosis. When the body temperature of < 37 ° C was maintained for 24 h, administration of antibiotics was stopped. The primary endpoint was the recurrence of acute cholangitis within 3 days after the withdrawal of antibiotic therapy. RESULTS: Eighteen patients were subjected to the final analysis. The causes of cholangitis were bile duct stone (n = 17) and bile duct cancer (n = 1). The severity of acute cholangitis was moderate in 14 patients and severe in 4. Body temperature of < 37 ° C was achieved in all patients after a median of 2 days (range 1-6) following endoscopic biliary drainage. Antibiotic therapy was administered for a median duration of 3 days (range 2-7). None of the patients developed recurrent cholangitis within 3 days after the withdrawal of antibiotics. CONCLUSIONS: Fever-based antibiotic therapy for acute cholangitis is safe and effective when resolution of fever is achieved following endoscopic biliary drainage.

A large volume of visceral adipose tissue leads to severe acute pancreatitis.

BACKGROUND: Obesity plays an important role in acute pancreatitis. Assuming that the volume of visceral adipose tissue (VAT) directly influences the severity of acute pancreatitis, we investigated the relationship between VAT and acute pancreatitis. METHODS: Data were collected consecutively from 124 patients who were diagnosed with acute pancreatitis. Body mass index (BMI) was calculated from the database. Computed tomography was performed in all patients, and VAT, subcutaneous adipose tissue (SAT), and waist circumference (WC) were measured at the level of the intervertebral disk between L2 and L3. Atlanta criteria were adopted to define severe acute pancreatitis. Clinical courses were investigated, and the Ranson and acute physiology and chronic health evaluation II (APACHE II) scores were calculated for all patients. RESULTS: Forty-eight patients had severe acute pancreatitis (38.7%), and 76 were mild cases. BMI, VAT, SAT, and WC were correlated with the severity of acute pancreatitis in a univariate analysis, but only VAT had a strong correlation with severe acute pancreatitis in the multivariate analysis. In a trend analysis, not only severity but also the presence of pseudocysts (local complication) and prognostic factors (Ranson and APACHE II scores) were significantly related to VAT volume. In particular, the presence of a pancreatic pseudocyst was strongly related to VAT volume (p < 0.001). CONCLUSION: In acute pancreatitis, peripancreatic VAT has a stronger correlation with severe acute pancreatitis than BMI or WC. VAT volume is strongly correlated with the formation of a pseudocyst and with systemic inflammatory response syndrome in patients with acute pancreatitis and high VAT volume may lead to severe acute pancreatitis.

An open-label, single-arm study assessing the efficacy and safety of L: -menthol sprayed onto the gastric mucosa during upper gastrointestinal endoscopy.

BACKGROUND AND AIMS: The results of a phase III, placebo-controlled study demonstrated that endoscopic direct spraying of L: -menthol onto the gastric mucosa effectively suppressed gastric peristalsis in the study patients. The aim of the study reported here was to determine whether the anti-peristaltic effect of an L: -menthol preparation facilitates endoscopic examinations in a clinical setting. METHODS: This was a multicenter, open-label, single-arm trial in which the study cohort comprised patients in whom L: -menthol was likely to be used to facilitate endoscopic examination in clinical settings. The primary outcome was the proportion of subjects with no peristalsis (Grade 1) after treatment and at the end of endoscopy (defined as the complete suppression of gastric peristalsis). This variable was assessed according to the level of anti-Helicobacter pylori immunoglobulin G (IgG) antibody, pepsinogen test results, whether sedation was performed, and whether subjects were considered unsuitable for the use of conventional antispasmodics. RESULTS: Of the 119 enrolled subjects, data from 112 were included in the primary efficacy analysis. Gastric peristalsis was completely suppressed in 37.5% of the patients [42/112 patients; 95% confidence interval (CI) 28.5-47.1]. Subgroup analyses revealed that the rate of peristalsis suppression was significantly higher in patients with elevated levels of anti-H. pylori IgG antibody (26/44, 59.1%; 95% CI 43.2-73.7); P < 0.001] and positive pepsinogen test results (21/35, 65.6%; 95% CI 46.8-81.4; P < 0.001]. There was no significant difference according to sedation (17/52, 32.7%; 95% CI 20.3-47.1; P = 0.434) or whether subjects were considered unsuitable for use of conventional antispasmodic agents (14/28, 50.0%; 95% CI 30.6-69.4; P = 0.12]. CONCLUSION: These findings are comparable to those of the phase III placebo-controlled study and provide further evidence that endoscopic direct spraying of L: -menthol effectively suppresses gastric peristalsis during upper gastrointestinal endoscopy.

Effect of vitamin K2 on the recurrence of hepatocellular carcinoma.

UNLABELLED: Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, even after curative treatment. Vitamin K2, which has been reported to reduce HCC development, may be effective in preventing HCC recurrence. Patients who underwent curative ablation or resection of HCC were randomly assigned to receive placebo, 45 mg/day, or 90 mg/day vitamin K2 in double-blind fashion. HCC recurrence was surveyed every 12 weeks with dynamic computed tomography/magnetic resonance imaging, with HCC-specific tumor markers monitored every 4 weeks. The primary aim was to confirm the superiority of active drug to placebo concerning disease-free survival (DFS), and the secondary aim was to evaluate dose-response relationship. Disease occurrence and death from any cause were treated as events. Hazard ratios (HRs) for disease occurrence and death were calculated using a Cox proportional hazards model. Enrollment was commenced in March 2004. DFS was assessed in 548 patients, including 181 in the placebo group, 182 in the 45-mg/day group, and 185 in the 90-mg/day group. Disease occurrence or death was diagnosed in 58, 52, and 76 patients in the respective groups. The second interim analysis indicated that vitamin K2 did not prevent disease occurrence or death, with an HR of 1.150 (95% confidence interval: 0.843-1.570, one-sided; P=0.811) between the placebo and combined active-drug groups, and the study was discontinued in March 2007. CONCLUSION: Efficacy of vitamin K2 in suppressing HCC recurrence was not confirmed in this double-blind, randomized, placebo-controlled study.

Specific increase in serum autotaxin activity in patients with pancreatic cancer.

OBJECTIVES: To evaluate the potential clinical significance of serum autotaxin (ATX) level in patients with cancers of the digestive system. DESIGN AND METHODS: Serum ATX activity was measured as the lysophospholipase D activity in patients with cancer of the esophagus (n=8), stomach (n=18), colorectum (n=21), biliary tract (n=19), or pancreas (n=103) and in patients with benign pancreatic diseases (n=73). RESULTS: Among patients with various cancers of digestive system, increased serum ATX activity was predominantly observed among pancreatic cancer patients. Serum ATX activity was not increased in patients with chronic pancreatitis or pancreatic cysts. In the diagnosis of pancreatic cancer, the area under the receiver operating curve for serum ATX activity was 0.541 (95% CI, 0.435-0.648) for men and 0.772 (95% CI, 0.659-0.885) for women. No significant correlation was observed between serum ATX activity and CEA, CA19-9 or Dupan2 levels. CONCLUSION: Serum ATX activity may be useful for identifying pancreatic cancer when used together with other serum markers of pancreatic cancer.

Surveillance of small intestinal abnormalities in patients with hepatocellular carcinoma: a prospective capsule endoscopy study.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) sometimes suffer from obscure gastrointestinal bleeding. Portal hypertension (PH), common in cirrhosis, induces esophagogastric varices. Because of the location, PH also may influence mucosal abnormalities in the small intestine. The objective of this study is to estimate the prevalence of small intestinal mucosal abnormalities in HCC patients using capsule endoscopy (CE). PATIENTS AND METHODS: We prospectively conducted CE in HCC patients, and analyzed the findings in relation to hepatic function, the number and size of HCC tumor and findings obtained by conventional endoscopy. RESULTS: Thirty-six patients (aged 66.7 ± 7.5 years, 29 men) underwent CE. Abnormal findings in the small bowel were found in 16 patients (44%), angioectasias in eight patients (22%), erosions in five (14%), varices in four (11%), polyps in four (11%), and submucosal tumor in one (3%). The patients with angioectasia had a larger spleen index than the no abnormal lesions group (85.4 ± 15.8 vs 59.0 ± 24.4, P = 0.02). The former group had been more frequently treated for esophageal varices endoscopically (62% vs 15%, P = 0.02). Large HCC nodules seemed more common in the patients with angioectasia than subjects without abnormal lesions (38% vs 5%, P = 0.06). Small intestinal varices also seemed to have a positive association with large HCC. During the follow up after CE, one patient with small intestinal polyps suffered from obscure gastrointestinal bleeding. CONCLUSIONS: CE revealed that HCC patients frequently have small intestinal mucosal lesions. In particular, small intestinal angioectasia, which may cause obscure gastrointestinal bleeding, seems to be associated with portal hypertension.

Single-balloon versus double-balloon endoscopy for achieving total enteroscopy: a randomized, controlled trial.

BACKGROUND: Balloon endoscopy has been accepted as an effective tool for examining the small intestine. Two types of balloon endoscopy, single and double, are commercially available. The difference in performance between these 2 types of balloon endoscopy has not yet been elucidated. OBJECTIVE: To compare the yield of single-balloon endoscopy (SBE) and double-balloon endoscopy (DBE). DESIGN: Single-center, randomized, controlled trial. SETTING: University hospital in Tokyo, Japan. PATIENTS: Patients with suspected small-bowel disease. INTERVENTIONS: SBE and DBE. MAIN OUTCOME MEASUREMENTS: Outcomes were the total enteroscopy rate, diagnostic yield, complication rate, and clinical outcomes. Analysis was done by intent to treat. RESULTS: The study started in April 2008 and was terminated in April 2010 because of an obvious disadvantage for the SBE group. Thirty-eight patients were enrolled in the study; 18 patients were assigned to the SBE group and 20 to the DBE group. The total enteroscopy rate was 0% in the SBE group and 57.1% in the DBE group (P = .002). In terms of complications, the DBE group had 1 patient with Mallory-Weiss syndrome, and the SBE group had 1 patient with hyperamylasemia. There was no difference in the overall diagnosis rate between the SBE and DBE groups (61.1% vs 50.0%, P = .49). There was no difference in therapeutic outcome between the SBE and DBE groups (27.8% vs 35.0%, P = .63). LIMITATIONS: Relatively small number of study patients. CONCLUSIONS: Total enteroscopy is more easily performed with DBE than with SBE.

New method of covered wallstents for distal malignant biliary obstruction to reduce early stent-related complications based on characteristics.

AIM: We previously reported a low occlusion rate with covered Wallstents for malignant biliary obstruction, but stent-related complications other than occlusion posed a problem. A modified covered Wallstent insertion method based on stent characteristics was evaluated to reduce stent-related complications. METHODS: A total of 138 patients with distal malignant biliary obstruction received covered Wallstent placement. From October 2001 to October 2003, 69 patients received covered Wallstent placement (Group 1). Thereafter, we modified our stent insertion method and 69 patients received stent placement using this modified method from November 2003 to January 2007 (Group 2). The modified insertion method consists of endoscopic sphincterotomy carried out in patients without pancreatic duct invasion and longer stent placement with the center of the stent located in the center of the biliary stricture to prevent pancreatitis, kinking of the bile duct, and stent dislocation. A comparative analysis was carried out using prospectively collected data in these two cohorts. RESULTS: Tumor ingrowth was not observed, and stent occlusion rate was 18.8% in Group 1 and 23.2% in Group 2. The overall rates of stent-related complications did not differ (39.1% in Group 1 and 30.4% in Group 2), but stent-related complications within 3months decreased from 22 episodes in Group 1 to 13 episodes in Group 2. Median event-free survival was prolonged by modified stent insertion method (125days in Group 1 and 268days in Group 2, P=0.020), although cumulative survival and stent patency were not significantly different. CONCLUSIONS: Our modified method of covered Wallstent placement showed improved event-free survival.

A phase I/II trial of the oral antiangiogenic agent TSU-68 in patients with advanced hepatocellular carcinoma.

PURPOSE: We studied the safety and effectiveness of TSU-68, an oral tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor and fibroblast growth factor receptor, in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients with unresectable or metastatic HCC were eligible for enrollment. In phase I, the safety, tolerability and pharmacokinetics were assessed in patients stratified based on liver function, from no cirrhosis to Child-Pugh class B. The safety and effectiveness were assessed in phase II at the dose determined in phase I. RESULTS: Twelve patients were enrolled in phase I. Dose-limiting toxicities were found with TSU-68 at the dose of 400 mg bid in Child-Pugh B patients, and 200 mg bid was established as the phase II dose. Phase II included 23 additional patients, and the safety and efficacy were evaluated in a total of 35 patients. One patient (2.9%) had a complete response. Two patients (5.7%) had a partial response, and 15 patients (42.8%) showed a stable disease. The median time to progression was 2.1 months, and the median overall survival was 13.1 months. Common adverse events were hypoalbuminemia, diarrhea, anorexia, abdominal pain, malaise, edema and AST/ALT elevation. The analysis of angiogenesis-related parameters suggests that serum-soluble vascular cell adhesion molecule-1 is a possible marker to show the response. CONCLUSIONS: TSU-68 at a dose of 200 mg bid determined by stratification into liver function, showed promising preliminary efficacy with a high safety profile in patients with HCC who had been heavily pre-treated.

Increased liver elasticity in patients with biliary obstruction.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.01). In 24 patients from the OJ group, transient elastography was performed before and after biliary drainage; there was a marked reduction in the elasticity after the procedure in these patients (p < 0.01). CONCLUSIONS: Liver elasticity increases in patients with biliary obstruction. This increase is reduced after biliary drainage, implying that the increased FibroScan® values before drainage are not due to liver fibrosis, but to temporarily increased elasticity.

Experiences of biliary interventions using short double-balloon enteroscopy in patients with Roux-en-Y anastomosis or hepaticojejunostomy.

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.

A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer.

Endoscopic papillary balloon dilation for bile duct stone removal in patients 60 years old or younger.

BACKGROUND: 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. METHODS: 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). RESULTS: 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%). CONCLUSION: 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.

Bezafibrate for the treatment of primary sclerosing cholangitis.

BACKGROUND: It is known that bezafibrate decreases serum alkaline phosphatase (ALP) in patients with hyperlipidemia, and the efficacy of this drug for the treatment of primary biliary cirrhosis has been confirmed. However, there has been little evidence of its efficacy for the treatment of primary sclerosing cholangitis (PSC). METHODS: Bezafibrate (400 mg/day) was orally administered to 7 consecutive patients with PSC, and we analyzed their clinical features and the drug efficacy in terms of the effect on hepatobiliary enzymes, including ALP, gamma-glutamyl transpeptidase (gamma-GTP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) after 6 months. The latest hepatobiliary enzyme levels were also evaluated. RESULTS: In 3 patients (effective group), the levels of all hepatobiliary enzymes had decreased after 6 months. Mean ALP had decreased to approximately 40% of the baseline in this group. The efficacy of bezafibrate was observed for a long period (range, 8-27 months) in these 3 patients. There seemed to be no definite association between the efficacy of bezafibrate and the clinical features in the short term. CONCLUSIONS: This study showed that bezafibrate could lower the levels of hepatobiliary enzymes in about half of a cohort of patients with PSC.

Endoscopic management of biliocutaneous fistula after percutaneous radiofrequency ablation therapy for hepatocellular carcinoma.

Our patient was a 70-year-old man with hepatocellular carcinoma (HCC) and liver cirrhosis (Child-Pugh B). He had a history of distal gastrectomy with Billroth II reconstruction for duodenal ulcer and hepatectomy for HCC. One month after percutaneous radiofrequency ablation (RFA) for recurrent HCC, biliocutaneous fistula was observed. The cholangiogram demonstrated leakage of contrast material from an intrahepatic duct into the fistula, and a nasobiliary catheter was placed. Subsequently, the discharge of bile steadily decreased and stopped. Follow-up cholangiogram revealed no evidence of bile leakage. Biliocutaneous fistula is an extremely rare complication after percutaneous RFA, and the present case report suggests that endoscopic drainage is the first-line therapy for bile leaks after RFA.

Macroscopic morphologic subtypes of laterally spreading colorectal tumors showing distinct molecular alterations.

Recent advances in colonoscopic techniques have resulted in more frequent detection of superficial-type colorectal tumors, that is, laterally spreading tumors (LSTs), although little is known about the characteristic clinical features and genetic alterations of LSTs. To elucidate the molecular characteristics of LSTs, genetic alterations in the KRAS, BRAF and PIK3CA genes and abnormal expression of the p53, beta-catenin and MYC proteins were analyzed using direct DNA sequencing and immunohistochemistry for 50 protruded-type tumors (Protruded), 35 granular-type LSTs (LST-G) and 19 nongranular-type LSTs (LST-NG). In addition, loss of heterozygosity (LOH) close to the adenomatous polyposis coli (APC) gene (5q21) was examined in these tumors. In univariate analyses, significant differences were noted in the percentages with KRAS mutations (Protruded, LST-G, LST-NG = 30.0%, 54.3%, 21.1%, respectively, p = 0.0156), nuclear accumulation of beta-catenin (Protruded, LST-G, LST-NG = 50.0%, 37.1%, 68.4%, respectively, p = 0.0267), expression of MYC (Protruded, LST-G, LST-NG = 26.0%, 17.1%, 42.1%, respectively, p = 0.0456) and LOH at the APC gene locus (Protruded, LST-G, LST-NG = 22.0%, 20.0%, 47.4%, respectively, p = 0.0302). Multivariate analysis demonstrated that the macroscopic subtype of LST was significantly associated with KRAS mutation (for LST-NG: odds ratio [OR] 0.23, 95% CI 0.06-0.90) and nuclear accumulation of beta-catenin (for LST-NG: OR 4.05, 95% CI 1.11-14.8). Our data revealed that the 2 subtypes of LST have different molecular characteristics, suggesting that 2 or more different molecular mechanisms result in colorectal tumors with a similar growth pattern.