Efficacy of a metallic stent covered with a paclitaxel-incorporated membrane versus a covered metal stent for malignant biliary obstruction: a prospective comparative study.

BACKGROUND: The placement of a self-expandable metallic stent (SEMS) is a widely used nonsurgical treatment method in patients with unresectable malignant biliary obstructions but SEMS is susceptible to occlusion by tumor ingrowth or overgrowth. AIM: The efficacy and safety of a metallic stent covered with a paclitaxel-incorporated membrane (MSCPM) in which paclitaxel provided an antitumoral effect was compared prospectively with those of a covered metal stent (CMS) in patients with malignant biliary obstructions. METHODS: Patients with unresectable distal malignant biliary obstructions (n = 106) were prospectively enrolled in this study at multiple treatment centers. A MSCPM was inserted endoscopically in 60 patients, and a CMS was inserted in 46 patients. Patients underwent systemic chemotherapy regimens alternatively according to disease characteristics. RESULTS: The two groups did not differ significantly in mean age, male to female ratio, or mean follow-up period. Stent occlusion due to tumor ingrowth occurred in 12 patients who received MSCPMs and in eight patients who received CMSs. Stent patency and survival time did not differ significantly between the two groups (p = 0.116, 0.981). Chemotherapy had no influence on stent patency, but gemcitabine-based chemotherapy was a significant prognostic factor for survival time (p = 0.012). Complications, including cholangitis and pancreatitis, were found to be acceptable in both groups. CONCLUSIONS: Although the use of a MSCPM produced no significant differences in stent patency or patient survival in patients with malignant biliary obstructions compared with the use of a CMS, this study demonstrated that MSCPM can be used safely in humans.

Factors predictive of adverse events following endoscopic papillary large balloon dilation: results from a multicenter series.

BACKGROUND: Lack of established guidelines for endoscopic papillary large balloon dilation (EPLBD) may be a reason for aversion of its use in removal of large common bile duct (CBD) stones. AIMS: We sought to identify factors predictive of adverse events (AEs) following EPLBD. METHODS: This multicenter retrospective study investigated 946 consecutive patients who underwent attempted removal of CBD stones ≥10 mm in size using EPLBD (balloon size 12-20 mm) with or without endoscopic sphincterotomy (EST) at 12 academic medical centers in Korea and Japan. RESULTS: Ninety-five (10.0 %) patients exhibited AEs including bleeding in 56, pancreatitis in 24, perforation in nine, and cholangitis in six; 90 (94.7 %) of these were classified as mild or moderate in severity. There were four deaths, three as a result of perforation and one due to delayed massive bleeding. Causative factors identified in fatal cases were full-EST and continued balloon inflation despite a persistent waist seen fluoroscopically. Multivariate analyses showed that cirrhosis (OR 8.03, p = 0.003), length of EST (full-EST: OR 6.22, p < 0.001) and stone size (≥16 mm: OR 4.00, p < 0.001) were associated with increased bleeding, and distal CBD stricture (OR 17.08, p < 0.001) was an independent predictor for perforation. On the other hand, balloon size was associated with deceased pancreatitis (≥14 mm: OR 0.27, p = 0.015). CONCLUSIONS: EPLBD appears to be a safe and effective therapeutic approach for retrieval of large stones in patients without distal CBD strictures and when performed without full-EST.

The increase in balloon size to over 15 mm does not affect the development of pancreatitis after endoscopic papillary large balloon dilatation for bile duct stone removal.

BACKGROUND: Endoscopic papillary large balloon dilatation (EPLBD) after endoscopic sphincterotomy (EST) has recently become widely used for common bile duct (CBD) stone removal, but many clinicians remain concerned about post-procedural pancreatitis with increasing the balloon size to over 15 mm. AIMS: We aimed to evaluate the safety and efficacy of EPLBD with a relatively large balloon (15-20 mm) after EST and to evaluate the factors related to post-EPLBD pancreatitis. METHODS: A retrospective review was undertaken of the endoscopic database of 101 patients with CBD stones who underwent EPLBD using a larger balloon size of over 15 mm (15-20 mm). Clinical parameters, endoscopic data, and outcomes were analyzed. RESULTS: The mean age of the subjects was 69 years. All patients had a dilated CBD of over 11 mm (mean = 22.6 mm). The mean size of balloon used in EPLBD was 17.1 ± 1.9 mm (range 15-20 mm). Mechanical lithotripsy was required in seven patients (6.9%). The rate of complete stone removal in the first session was 92.1%. Post-procedural pancreatitis developed in five cases (5.4%), but none were graded as severe. The smaller dilatation of the CBD, longer cannulation time, and longer time for stone removal were associated with post-procedural pancreatitis, but larger size of balloon did not affect the development of post-EPLBD pancreatitis. CONCLUSIONS: EPLBD with a large balloon of over 15 mm with EST is an effective and safe procedure with a very low probability of severe post-procedural pancreatitis. Post-EPLBD pancreatitis was not associated with larger balloon size, but was associated with longer procedure time and smaller dilatation of the CBD.

Endoscopic Vacuum Therapy in Patients with Transmural Defects of the Upper Gastrointestinal Tract: A Systematic Review with Meta-Analysis.

A transmural defect of the upper gastrointestinal (UGI) tract is a life-threatening condition associated with high morbidity and mortality. Recently, endoscopic vacuum therapy (EVT) was used for managing UGI defects and showed promising results. We conducted a systematic review and meta-analysis to synthesize evidence on the efficacy of EVT in patients with transmural defects of the UGI tract. We searched the PubMed, Cochrane Library, and Embase databases for publications on the effect of EVT on successful closure, mortality, complications, and post-EVT strictures. Methodological quality was assessed using the Newcastle-Ottawa quality assessment scale. This meta-analysis included 29 studies involving 498 participants. The pooled estimate rate of successful closure with EVT was 0.85 (95% confidence interval [CI]: 0.81-0.88). The pooled estimate rates for mortality, complications, and post-EVT strictures were 0.11, 0.10, and 0.14, respectively. According to the etiology of the transmural defect (perforation vs. leak and fistula), no significant difference was observed in successful closure (odds ratio [OR]: 1.45, 95% CI: 0.45-4.67, p = 0.53), mortality (OR: 0.77, 95% CI: 0.24-2.46, p = 0.66), complications (OR: 0.94, 95% CI: 0.17-5.15, p = 0.94), or post-EVT stricture rates (OR: 0.70, 95% CI: 0.12-4.24, p = 0.70). The successful closure rate was significantly higher with EVT than with self-expanding metal stent (SEMS) placement (OR: 3.14, 95% CI: 1.23-7.98, p = 0.02). EVT is an effective and safe treatment for leaks and fistulae, as well as for perforations in the UGI. Moreover, EVT seems to be a better treatment option than SEMS placement for UGI defects.

Outcome of adjuvant therapy for gallbladder cancer.

OBJECTIVES: The aim of this study was to evaluate the outcome of adjuvant therapy on the overall survival (OS) and disease-free survival (DFS) after curative resection (RO) of patients with TNM stage II gallbladder (GB) cancer. METHODS: A total of 160 patients who had received curative resection (RO) between January 2000 and December 2009 were retrospectively reviewed. Among 61 stage II GB cancer patients, 43 received adjuvant therapy, while 18 others received surgery alone. The median follow-up period was 27.3 months (range 2.2-98.9 months). RESULTS: OS was not significantly different among the adjuvant therapies (p = 0.180), but DFS was (p = 0.033). The 3-year OS and DFS from surgery alone, adjuvant chemotherapy, adjuvant radiotherapy, and adjuvant concurrent chemo-radiotherapy were 64, 78, 36 and 36%, and 56, 69, 14 and 47%, respectively. Overall, the chemotherapy group had a better prognosis, although there were no significant differences. CONCLUSIONS: The data from this study do not provide evidence that adjuvant therapy is an effective treatment option for curative resected GB cancer. A large randomized controlled study is necessary to confirm the efficacy of adjuvant therapy. Newer adjuvant studies should be focused on gemcitabine-based chemotherapy or chemo-radiotherapy with molecular-based target agents.

[Extrapancreatic tumors in intraductal papillary mucinous neoplasm of the pancreas].

BACKGROUND/AIMS: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a favorable prognosis, but seems to be associated with a high incidence of extrapancreatic tumors. The purpose of this study was to evaluate the incidence and clinicopathological features of extrapancreatic tumors associated with IPMN. METHODS: Thirty-seven patients with IPMN of the pancreas, confirmed by surgical resection and typical findings of endoscopic ultrasonography and CT imaging between October 1, 1998 and August 31, 2006 were included. Seventeen patients were diagnosed with surgical resection and biopsy, and others by typical imaging findings of IPMN. These patients were examined for the development of extrapancreatic tumors. RESULTS: Of 37 patients with IPMN, 14 (38%) had 18 extrapancreatic tumors, and 10 (27%) had 13 extrapancreatic malignancies. Five, six, and two extrapancreatic malignancies had been diagnosed before, during, and after the diagnosis of IPMN. Gastric adenocarcinoma (3 patients, 23%) and colorectal carcinoma (3 patients, 23%) were the most common neoplasms. Other extrapancreatic tumors included lung cancer (n=2), prostatic cancer (n=1), renal cell carcinoma (n=1), cholangiocellular carcinoma (n=1), urinary bladder cancer (n=1), and gallbladder cancer (n=1), respectively. As benign tumor, there were two gallbladder adenoma, one gastric adenoma, one colonic adenoma and one benign ovarian cystic neoplasm, respectively. CONCLUSIONS: IPMN is associated with high incidence of extrapancreatic tumors, particularly gastric and colorectal neoplasms. Upper gastrointestinal endoscopy and colonoscopy should be done, and systemic surveillance for the possible occurrence of other tumors may allow early detection of extrapancreatic tumor in patients with IPMN.

Salvage chemotherapy with docetaxel and epirubicin for advanced/metastatic gastric cancer.

BACKGROUND: We conducted a phase II study to assess the efficacy and tolerability of docetaxel and epirubicin as salvage chemotherapy in advanced/metastatic gastric cancer patients with documented progression after 5-fluorouracil/platinum-based combination chemotherapy. METHODS: Docetaxel 75 mg/m(2) and epirubicin 50 mg/m(2) were administered on days 1 and 2, respectively, every 3 weeks. Treatment continued until progression of disease or until a life-threatening adverse event occurred. The primary objectives of this study were to evaluate the safety profile and response rate to this treatment regimen. RESULTS: Thirty-four patients were enrolled in the study. Twenty-six patients had locally advanced or metastatic disease at the time of diagnosis, and 8 patients had recurrent disease after surgical resection of the primary tumor. A total of 157 chemotherapy cycles were administered. Seven (21.8%) patients had a partial response and 12 (37.5%) patients had stable disease. The median time to progression and overall survival were 4.1 and 13.4 months, respectively. Grade III/IV hematologic toxicities included neutropenia in 16 patients (47%) and febrile neutropenia in 8 patients (24%). Nonhematologic toxicities were rare. CONCLUSION: A combination of chemotherapy with docetaxel and epirubicin showed moderate activity as salvage treatment in advanced/metastatic gastric cancer, especially in patients who had responded to prior chemotherapy.

Common bile duct stones associated with pancreatobiliary reflux and disproportionate bile duct dilatation.

Occult pancreatobiliary reflux (PBR) in patients with a normal pancreatobiliary junction has been studied by various methods, but the exact etiology, mechanisms, and implications of this reflux have not yet been clarified. The aim of this study was to investigate the degree of PBR and patterns of biliary ductal dilatation in patients with acute calculous cholangitis by endoscopic retrograde cholangiopancreatography (ERCP).We retrospectively evaluated the degree of PBR and pattern of bile duct dilatation in patients with acute calculous cholangitis due to distal CBD (common bile duct) stones (Group A) as compared with patients with malignant CBD obstruction due to distal CBD cancer (Group B). All related data were prospectively collected. Bile juice was aspirated at the proximal CBD for measurement of biliary amylase and lipase before the injection of contrast dye. The diameters of the CBD and the peripheral intrahepatic duct (IHD) were calculated after contrast dye injection. Patients with pancreatobiliary maljunction and/or gallstone pancreatitis were excluded from the study.ERCP was performed on 33 patients with calculous cholangitis (Group A) and 12 patients with malignant CBD obstruction (Group B). Mean levels of bile amylase and lipase were significantly higher (P < .05) in group A (1387 and 6737 U/l, respectively) versus those in group B (32 and 138 U/l, respectively). Thirty patients in group A (90.9%) showed disproportionate dilatation (i.e., CBD was and IHD was not dilated), whereas only 4 patients in group B (33%) showed disproportionate dilatation.The results of this study suggest that patients with calculous cholangitis exhibit PBR that is associated with disproportionate bile duct dilatation.

Efficacy of a Multiplex Paclitaxel Emission Stent Using a Pluronic® Mixture Membrane versus a Covered Metal Stent in Malignant Biliary Obstruction: A Prospective Randomized Comparative Study.

BACKGROUND/AIMS: A drug-eluting stent for unresectable malignant biliary obstruction was developed to increase stent patency by preventing tumor ingrowth. The safety and efficacy of a new generation of metallic stents covered with a paclitaxel-incorporated membrane using a Pluronic® mixture (MSCPM-II) were compared prospectively with those of covered metal stents (CMSs) in patients with malignant biliary obstructions. METHODS: This study was initially designed as a prospective randomized trial but was closed early because of a high incidence of early occlusion. Therefore, the data were analyzed using the intent-to-treat method. A total of 72 patients with unresectable distal malignant biliary obstructions were prospectively enrolled. RESULTS: The two groups did not differ significantly in basic characteristics and mean follow-up period (MSCPM-II 194 days vs CMS 277 days, p=0.063). Stent occlusion occurred in 14 patients (35%) who received MSCPM-II and in seven patients (21.9%) who received CMSs. Stent patency and survival time did not significantly differ between the two groups (p=0.355 and p=0.570). The complications were mild and resolved by conservative management in both groups. CONCLUSIONS: There were no significant differences in stent patency or patient survival in MSCPM-II and CMS patients with malignant biliary obstructions.

Prognostic Factors and Scoring Model for Survival in Metastatic Biliary Tract Cancer.

PURPOSE: Metastatic biliary tract cancer (mBTC) has a dismal prognosis. In this study, an independent dataset of patients with mBTC was used to implement and validate a routine clinico-laboratory parameter-based scoring model for risk group identification. MATERIALS AND METHODS: From September 2006 to February 2015, 482 patients with mBTC were assigned randomly (ratio, 7:3) into investigational (n=340) and validation datasets (n=142). The continuous variables were dichotomized using a normal range or the best cutoff values determined using the Contal and O'Quigley statistical methods. Following a Cox's proportional hazard model, the scoring model was derived by summing the rounded chi-square scores for the factors identified by multivariate analysis. RESULTS: The performance status (Eastern Cooperative Oncology Group 3-4), hypoalbuminemia (< 3.4 mg/dL), carcinoembryonic antigen (≥ 9 ng/mL), neutrophil-to-lymphocyte ratio (≥ 3.0), and carbohydrate antigen 19-9 (≥ 120 U/mL) were identified as independent prognosticators (Harrell's C index, 0.682; integrated area under the curve, 0.653). Survival was clearly correlated with the risk groups (low, intermediate, and high, 14.0, 7.3, and 2.3 months, respectively; p < 0.001). The prognosis was also discriminative in the validation data set (median survival, 16.7, 7.5, and 1.9 months, respectively; p < 0.001). Chemotherapy did not offer any survival benefits for high-risk patients. CONCLUSION: These proposed prognostic criteria for mBTC can facilitate accurate patient risk stratification and treatment-related decision-making.

Factors affecting long-term clinical outcomes of endoscopic mucosal resection of early gastric cancer.

BACKGROUND/AIMS: Endoscopic mucosal resection (EMR) has been widely accepted as a treatment option for early gastric cancer (EGC) in selected cases. The purposes of this study were to evaluate the long-term outcomes and the factors affecting the clinical outcomes, of EMR performed in EGC. METHODOLOGY: Between April 1996 and March 2005, 147 patients have undergone EMR to treat EGC at Yonsei University Medical Center, Seoul, Korea. We assessed the clinical outcomes of the EMR for EGC in a long-term follow-up period. We also reviewed the medical records of the patients including demographic data, endoscopic characteristics of the lesion and histopathologic findings. RESULTS: The histopathologic evaluations after the EMR treatment showed that overall complete resection rate was 84.6% (126/149) while complete resec tion rate of 93.5% was achieved in mucosal cancers (115/123). The success of complete resection was significantly affected by endoscopic gross type (depressed lesion), the degree of differentiation, and the depth of invasion, independently. There were only 5 cases of local recurrence during the follow-up periods, and the recurred or incompletely resected lesions were successfully treated by salvage operation or endoscopic retreatment. There was no disease-related or treatment-related mortality during the follow-up period. CONCLUSIONS: EMR is a good and safe curative treatment option with feasible clinical outcomes in patients with EGC. It must be emphasized that a proper selection of candidates is mandatory to improve the clinical outcome of EMR in EGC.

Generation of nitric oxide in the opossum lower esophageal sphincter during physiological experimentation.

Lipopolysaccharide (LPS), given in vivo, modulates opossum esophageal motor functions by inducing the inducible nitric oxide synthase (iNOS), which increases nitric oxide (NO) production. Superoxide, a NO scavenger, is generated during this endotoxemia. Superoxide is cleared by superoxide dismutase (SOD) and catalase (CAT) to protect the physiological function of NO. This study examined whether lower esophageal sphincter (LES) motility, NO release, and iNOS and nitrotyrosine accumulation in the LES are affected by LPS in vitro. Muscle strips from the opossum LES were placed in tissue baths containing oxygenated Krebs buffer. NO release was measured with a chemiluminescence NOx analyzer, and Western blots were performed to analyze iNOS and nitrotyrosine production. The percent change in resting LES tone after a 6-hour exposure to LPS was significantly increased compared to pretreatment values. The percent LES relaxation upon electrical stimulation was significantly decreased in the control group at 6 hours, indicating that the LPS treatment had an effect. The NO concentration in the tissue bath of LPS- treated muscle without nerve stimulation was significantly less than that of LPS treatment combined with SOD/CAT or SOD/CAT alone. iNOS and nitrotyrosine were detectable and increased over time in the LES muscle of both the control and LPS-treated groups. Antioxidant enzymes may play a role in regulating NO-mediated neuromuscular functions in the LES.

Prognostic Scoring Index for Patients with Metastatic Pancreatic Adenocarcinoma.

PURPOSE: This study focused on implementation of a prognostic scoring index based on clinico-laboratory parameters measured routinely on admission in metastatic pancreatic cancer patients. MATERIALS AND METHODS: Records from 403 patients of metastatic disease were analyzed retrospectively. Continuous variables were dichotomized according to the normal range or the best cut-off values statistically determined by Contal and O'Quigley method, and then analyzed in association with prognosis-overall survival (OS), using Cox's proportional hazard model. Scores were calculated by summing the rounded chi-square scores for the factors that emerged in the multivariate analysis. RESULTS: Performance status, hemoglobin, leucocyte count, neutrophil-lymphocyte ratio, and carcinoembryonic antigen were independent factors for OS. When patients were divided into three risk groups according to these factors, median survival was 11.7, 6.2, and 1.3 months for the low, intermediate, and high-risk groups, respectively (p < 0.001). Palliative chemotherapy has a significant survival benefit for low and intermediate-risk patients (median OS; 12.5 months vs. 5.9 months, p < 0.001 and 8.0 months vs. 2.0 months, p < 0.001, respectively). CONCLUSION: We advocate the use of a multivariable approach with continuous variables for prognostic modeling. Our index is helpful in accurate patient risk stratification and may aid in treatment selection.

Clinicopathological features of choledocholithiasis patients with high aminotransferase levels without cholangitis: Prospective comparative study.

Common bile duct (CBD) stones are generally associated with greater elevations of alkaline phosphatase and gamma-glutamyl transpeptidase levels than aspartate aminotransferase and alanine aminotransferase levels. However, some patients with CBD stones show markedly increased aminotransferase levels, sometimes leading to the misdiagnosis of liver disease. Therefore, the aim of this study was to investigate the clinicopathologic features of patients with CBD stones and high aminotransferase levels.This prospective cohort study included 882 patients diagnosed with CBD stones using endoscopic retrograde cholangiopancreatography (ERCP). Among these patients, 38 (4.3%) exhibited aminotransferase levels above 400 IU/L without cholangitis (gallstone hepatitis [GSH] group), and 116 (13.2%) exhibited normal aminotransferase levels (control group). We compared groups in terms of clinical features, laboratory test results, radiologic images, and ERCP findings such as CBD diameter, CBD stone diameter and number, and periampullary diverticulum. Liver biopsy was performed for patients in the GSH group.GSH patients were younger and more likely to have gallbladder stones than control patients, implying a higher incidence of gallbladder stone migration. Also, GSH patients experienced more severe, short-lasting abdominal pain. ERCP showed narrower CBDs in GSH patients than in control patients. Histological analysis of liver tissue from GSH patients showed no abnormalities except for mild inflammation.Compared with control patients, GSH patients were younger and showed more severe, short-lasting abdominal pain, which could be due to a sudden increase of CBD pressure resulting from the migration of gallstones through narrower CBDs. These clinical features could be helpful not only for the differential diagnosis of liver disease but also for investigating the underlying mechanisms of liver damage in obstructive jaundice. Moreover, we propose a new definition of "gallstone hepatitis" based on the specific clinicopathologic characteristics observed in our patients.

The diagnostic value of endoprobe for small esophageal leiomyomas derived from the muscularis mucosae.

Esophageal leiomyoma derived from the muscularis mucosae (MM) is a rare condition, and the optimal modality for diagnosis and treatment is controversial. Endoscopic ultrasonography can provide an accurate image of esophageal layer structure, providing information on lesion suitability for potential endoscopic therapy. We attempted to investigate the diagnostic value of a transendoscopic balloon-tipped miniature ultrasonic endoprobe for small esophageal leiomyomas derived from MM. We resected 7 small esophageal leiomyomas derived from MM by endoscopic mucosal resection (EMR), all of which were diagnosed by a balloon-tipped endoprobe. The endosonographic and pathologic features of 7 cases of small esophageal leiomyomas derived from MM were compared. The balloon-tipped endoprobe clearly showed all 7 small esophageal leiomyomas derived from MM, even those under 5 mm in size (smallest lesion, 3.0 mm). The endosonographic characteristics of small esophageal leiomyomas derived from MM were a hypoechoic mass with smooth, regular, and a well-defined outer margin and homogenous inner echogram arising from the second hypoechoic layer. Complete resections were possible in all 7 cases by EMR without any complications. Tumor size was 3.0-13.5 mm (mean 7.8 mm) in maximum diameter. In all cases, endosonographic findings by endoprobe were exactly concordant with pathologic finding in determining the tumors depth in the esophageal wall, tissue origin and characteristics, growth pattern, and size. We detail the balloon-tipped endoprobe is a simple, convenient, and very useful in making accurate diagnosis of small esophageal leiomyomas derived from the MM and the appropriate applications of EMR.

A Phase II study of capecitabine combined with gemcitabine in patients with advanced gallbladder carcinoma.

Capecitabine and gemcitabine are used in the treatment of a variety of solid tumors including pancreatic and biliary tract carcinomas. The authors evaluated survival, response, and toxicity associated with using a combination of capecitabine and gemcitabine to treat patients with unresectable or metastatic gallbladder adenocarcinoma (GBC). Eligible patients had histologically- or cytologically-confirmed GBC, no prior systemic therapy with capecitabine or gemcitabine, Karnofsky Performance Status 70%, serum total bilirubin up to three times normal, and measurable disease. Treatment consisted of gemcitabine 1000 mg/m2 IV on Days 1 and 8 concurrent with administration of capecitabine 1000 mg/m2 PO BID on Days 1 through 14, on a 3-week cycle. Tumor response was assessed by the response evaluation criteria in solid tumors (RECIST criteria) and survival was calculated from initiation of CapGem therapy. A total of 24 patients were enrolled. Median age at the time of diagnosis was 62 years (range, 41-78 years). Fourteen patients had undergone prior surgery. Results showed that eight patients achieved partial response (33%) with an additional 10 patients achieving stable disease (42%). The overall median time to disease progression was 6.0 months (95% CI, 3.8-8.1 months) and overall survival was 16 months (95% CI, 13.8-18.3 months). The one-year survival rate was 58%. No Grade 4 toxicity was seen. Transient Grade 3 neutropenia/ thrombocytopenia and manageable nausea, hand-foot syndrome and anorexia were the most common toxicities. Our study shows that CapGem is an active and well-tolerated chemotherapy regimen in patients with advanced GBC.

Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study.

Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p = 0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0 --> 4.2, p = 0.000); lactulose group (11.3 --> 5.0, p = 0.000)). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.

Gemcitabine Combined with Capecitabine Compared to Gemcitabine with or without Erlotinib as First-Line Chemotherapy in Patients with Advanced Pancreatic Cancer.

PURPOSE: The purpose of this study is to retrospectively compare the efficacy and tolerability between three regimens for first-line chemotherapy-gemcitabine plus capecitabine (GEM-X), gemcitabine plus erlotinib (GEM-T), and gemcitabine monotherapy (GEM)-in patients with advanced pancreatic cancer. MATERIALS AND METHODS: There was a total of 127 patients who underwent chemotherapy for pancreatic cancer between January 2007 and November 2011 at our institution. Patients were treated with either GEM (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks), GEM-T (gemcitabine 1,000 mg/m(2) on days 1 and 8 every 3 weeks and erlotinib 100 mg daily), or GEM-X (gemcitabine 1,000 mg/m(2) on days 1 and 8 every 3 weeks and capecitabine 850 mg/m(2) twice daily for 2 weeks followed by 1 week's rest) as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity were evaluated. RESULTS: The patient population was divided into groups depending on their first-line treatment: GEM (n=47), GEM-T (n=44), and GEM-X (n=36). GEM-X significantly improved ORR (21.2% vs. 12.7% and 15.9%), PFS (8.9 vs. 5.2 and 3.9 months; p < 0.001), and OS (12.1 vs. 10.4 and 9.9 months; p = 0.03) compared to GEM and GEM-T, respectively. There were higher incidences of some non-hematologic adverse events with GEM-X and GEM-T compared to GEM, but most were grade 1 or 2. CONCLUSION: GEM-X presented better clinical efficacy and acceptable tolerability than GEM-T and GEM in advanced pancreatic cancers. It is worthy to further investigate which agent has a clinical advantage as a combination drug with gemcitabine in pancreatic cancer and to explore the predictive markers leading to personalize anti-cancer treatment.

[Type of electric currents used for standard endoscopic sphincterotomy does not determine the type of complications].

BACKGROUND/AIMS: The blended current is usually used for endoscopic sphincterotomy (EST) to minimize bleeding. The pure cutting current may induce less edema of the ampulla and therefore result in less injury to the pancreas theoretically. The aim of this study was to evaluate effects of electric currents used on the development of serum pancreatic enzyme evaluation, clinical pancreatitis or bleeding after EST. METHODS: One hundred and eighteen consecutive patients who underwent EST with standard papillotome alone for the treatment of choledocholithiasis were reviewed. All EST had been performed by two endoscopists whose experience on EST was similar: one uses 'blended current' (BC group, n=74), while the other uses 'pure cutting current' (PC group, n=44). RESULTS: Baseline clinical, laboratory, and procedural parameters were similar in both groups. The incidences of hyperamylasemia and hyperlipasemia were similar between two groups. There was no significant difference in the incidence of clinical pancreatitis between two groups (BC 6.8% vs PC 0.0%, p=0.1557). All episodes of pancreatitis were mild. No episodes of significant bleeding occurred after EST. The incidences of sepsis, cholangitis and perforation were also not different between two groups. CONCLUSIONS: Development of complications after standard EST such as hyperamylasemia, clinical pancreatitis, and bleeding may not depend on the electric current used.

[A case of duodenal adenocarcinoma arising from the heterotopic pancreas].

Heterotopic pancreas, defined as the presence of pancreatic tissue that lacks anatomic and vascular continuity with the pancreas proper, may be more likely to undergo malignant change. However, malignancy arising from heterotopic pancreas is rare. In Korea, only one case of adenocarcinoma arising from a gastric heterotopic pancreas has been reported. Recently, we experienced a case of duodenal carcinoma arising from heterotopic pancreas in a 64-year-old man. Endoscopic biopsy of the stenotic duodenum was positive for adenocarcinoma, and he underwent a pancreaticoduodenectomy with subtotal gastrectomy. Histologic examination of the resected specimen satisfied the proposed conditions that are necessary to prove that a malignancy arose from heterotopic pancreas. Despite an adjuvant chemotherapy, he died 10 months after surgery. Herein, we report a case of duodenal adenocarcinoma arising from heterotopic pancreas with a review of the relevant literature.