Identification of endoscopic predictors of biliary malignancy during digital cholangioscopy.

OBJECTIVES: Biliary brushings and biopsies obtained during endoscopic retrograde cholangiopancreatography (ERCP) have a low sensitivity for the diagnosis of malignant biliary strictures. While cholangioscopic analysis is useful, visual criteria have not yet been defined. The aim of this study was to identify visual criteria for the diagnosis of indeterminate biliary strictures (IDBS). METHODS: A multicenter study was conducted based on the analysis of cholangioscopic recordings of IBDS. Diagnostic criteria were identified in a study group and verified in a validation group. RESULTS: Four criteria were identified to be associated with malignancy, one negatively ("endobiliary material," odds ratio [OR] 0.62, 95% confidence interval [CI] 0.41-0.92) and three positively ("vascularized villous projections," OR 1.52, 95% CI 1.03-2.24; "twisted or dilated vessels," OR 2.18, 95% CI 1.47-3.24; and "dark color of the mucosa," OR 1.82, 95% CI 1.23-2.70). Between two playbacks, the mean (95% CI) sensitivity of the observer's visual diagnosis increased from 66.1% (60-72) to 73.8% (69-78) (P = 0.004); in the second playback, the kappa value for interobserver agreement ranged between 0.36 (color) and 0.56 (endobiliary material), with a significant improvement (P = 0.0031-0.0001) between the first and second playbacks. Blind assessment by endoscopists not involved in this study had a diagnostic accuracy of 73% (71.4-74.5). CONCLUSION: The four identified cholangioscopic features are easy to implement in clinical practice and have the potential to increase the level of diagnostic confidence during the workup of IDBS.

Endoscopic radiofrequency ablation or surveillance in patients with Barrett's oesophagus with confirmed low-grade dysplasia: a multicentre randomised trial.

OBJECTIVE: Due to an annual progression rate of Barrett's oesophagus (BO) with low-grade dysplasia (LGD) between 9% and 13% per year endoscopic ablation therapy is preferred to surveillance. Since this recommendation is based on only one randomised trial, we aimed at checking these results by another multicentre randomised trial with a similar design. DESIGN: A prospective randomised study was performed in 14 centres comparing radiofrequency ablation (RFA) (maximum of 4 sessions) to annual endoscopic surveillance, including patients with a confirmed diagnosis of BO with LGD. Primary outcome was the prevalence of LGD at 3 years. Secondary outcomes were the prevalence of LGD at 1 year, the complete eradication of intestinal metaplasia (CE-IM) at 3 years, the rate of neoplastic progression at 3 years and the treatment-related morbidity. RESULTS: 125 patients were initially included, of whom 82 with confirmed LGD (76 men, mean age 62.3 years) were finally randomised, 40 patients in the RFA and 42 in the surveillance group. At 3 years, CE-IM rates were 35% vs 0% in the RFA and surveillance groups, respectively (p<0.001). At the same time, the prevalence LGD was 34.3% (95% CI 18.6 to 50.0) in the RFA group vs 58.1% (95% CI 40.7 to 75.4) in the surveillance group (OR=0.38 (95% CI 0.14 to 1.02), p=0.05). Neoplastic progression was found in 12.5% (RFA) vs 26.2% (surveillance; p=0.15). The complication rate was maximal after the first RFA treatment (16.9%). CONCLUSION: RFA modestly reduced the prevalence of LGD as well as progression risk at 3 years. The risk-benefit balance of endoscopic ablation therapy should therefore be carefully weighted against surveillance in patients with BO with confirmed LGD. TRIAL REGISTRATION NUMBER: NCT01360541.

Impact of peroral cholangioscopy on the management of indeterminate biliary conditions: a multicentre prospective trial.

BACKGROUND AND AIMS: Single-operator cholangioscopy (SOC) can help diagnose biliopancreatic conditions. The impact of SOC on patient outcome has never been specifically addressed. PATIENTS AND METHODS: Consecutive patients bearing indeterminate biliary strictures (IDBS), or primary sclerosing cholangitis (PSC) with suspected cholangiocarcinoma, were included. Patients with IDBS had at least one previous inconclusive endoscopic retrograde cholangio pancreatography (ERCP) + cytology. Primary endpoint was the difference in adequacy of management planned before and after SOC with regard to final diagnosis obtained after surgery or 24 months follow-up. DESIGN: Prospective open-label multicentre trial. RESULTS: 61 patients were included (IDBS: 48; PSC: 13); 70.5% had a benign lesion (IDBS 66.7%, PSC 84.6%). The management adequacy rate was significantly higher after SOC than before SOC overall (p<10-5), in IDBS (p<0.001) and PSC (p<0.05) patients. SOC induced changes in the management of the majority of patients in all groups (60.3%). The overall sensitivity of combined visual impression and biopsy ranged from 52% to 63.6% depending on investigator or independent expert rating (κ 0.92-0.96), whereas specificity, positive and negative predictive values of SOC were, respectively, 100%, 100% and 83.6%. Patient management observed at the end of follow-up was consistent with that anticipated after SOC in 88.5% overall. CONCLUSION: Despite a moderate sensitivity for the diagnosis of malignancy, SOC has a dramatic impact on the management of patients with IDBS and PSC with suspected carcinoma. Cholangioscopy might be implemented in the workup of selected patients with challenging diagnosis, when a significant impact on outcome (essentially resection vs conservative management) is to be expected.

Postprandial bile acid levels in intestine and plasma reveal altered biliary circulation in chronic pancreatitis patients.

Bile acid (BA) secretion and circulation in chronic pancreatitis (CP) patients with exocrine pancreatic insufficiency (EPI) were investigated by simultaneously measuring postprandial levels of individual BAs in duodenal contents and blood plasma using LC-MS/MS. CP patients and healthy volunteers (HVs) were intubated with gastric and duodenal tubes prior to the administration of a test meal and continuous aspiration of duodenal contents. Pancreatic lipase outputs in CP patients were very low (0.7 ± 0.2 mg) versus HVs (116.7 ± 68.1 mg; P < 0.005), thus confirming the severity of EPI. Duodenal BA outputs were reduced in CP patients (1.00 ± 0.89 mmol; 0.47 ± 0.42 g) versus HVs (5.52 ± 4.53 mmol; 2.62 ± 2.14 g; P < 0.15). Primary to secondary BA ratio was considerably higher in CP patients (38.09 ± 48.1) than HVs (4.15 ± 2.37; P < 0.15), indicating an impaired transformation of BAs by gut microbiota. BA concentrations were found below the critical micellar concentration in CP patients, while a high BA concentration peak corresponding to gallbladder emptying was evidenced in HVs. Conversely, BA plasma concentration was increased in CP patients versus HVs suggesting a cholangiohepatic shunt of BA secretion. Alterations of BA circulation and levels may result from the main biliary duct stenosis observed in these CP patients and may aggravate the consequences of EPI on lipid malabsorption.

Efficacy and safety of pasireotide-LAR for the treatment of refractory bleeding due to gastrointestinal angiodysplasias: results of the ANGIOPAS multicenter phase II noncomparative prospective double-blinded randomized study.

BACKGROUND: Gastrointestinal angiodysplasias (GIADs) could be responsible for recurrent bleeding and severe anemia. Somatostatin analogs could reduce transfusion requirements in these patients but no randomized controlled study is available. The main objective of the ANGIOPAS phase II double-blinded randomized, noncomparative study was to assess the effectiveness of pasireotide-LAR in reducing transfusion requirements in patients with refractory GIADs bleeding. METHODS: A total of 22 patients with transfusion requirements ⩾6 units of packed red blood cells (pRBCs) during the 6 months prior to inclusion were randomized to receive pasireotide-LAR 60 mg (n = 10) or placebo (n = 12) every 28 days for 6 months. Patients were then followed for an additional 6 months after stopping treatment. RESULTS: The pasireotide-LAR and placebo groups were equivalent for age, sex, comorbidities and transfusion requirement during the reference period (median 13 and 9.5 pRBCs). A 50 and 83% success rate (success defined as a decrease of at least 30% of transfused pRBCs) was observed in the pasireotide-LAR arm in the Intent to Treat (ITT) and per protocol (PP) analysis respectively. The need for transfusion during the intervention period was 3 pRBC units in the pasireotide-LAR group (range 0-26) and 11.5 pRBC units in the placebo group (range 0-23). Overall, three cases with glycemic control impairment were observed in the pasireotide-LAR group including one de novo diabetes. CONCLUSION: This double-blinded noncomparative randomized phase II study suggests, for the first time, the effectiveness of pasireotide-LAR 60 mg every 28 days to decrease the transfusion requirement in patients with recurrent bleeding due to GIADs.

Clinical outcome after biliary drainage for metastatic colorectal cancer: Survival analysis and prognostic factors.

INTRODUCTION: Biliary obstruction secondary to colorectal cancer liver metastases is associated with a poor prognosis especially when chemotherapy cannot be re-started. The aim of this study was to determine the survival after biliary drainage and the associated prognostic factors. METHODS: Patients from two French centers were included retrospectively after first biliary endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography drainage for biliary obstruction secondary to liver metastases of colorectal cancer, occurring during chemotherapy. RESULTS: The final analysis included 69 patients. Overall median survival was 115 days. In univariate analysis, a previous liver surgery, technical and functional success of drainage and restarted chemotherapy were significantly associated with an improved survival. Chemotherapy was restarted after a median of 27 days. When drainage was efficient, survival improved from 33 to 262days (p<0.001). In multivariate analysis, significant protective factors for survival included previous a hepatectomy (HR 0.41) and functional success of the drainage (HR 0.29). Predictive factors for death included increased lines of chemotherapy (HR 1.68) and fever before drainage (HR 2.97). CONCLUSIONS: This is the first study concerning the benefits of biliary drainage for malignant biliary obstruction during the course of chemotherapy for colorectal cancer. A successful biliary drainage leads to improved survival and allows achievement of chemotherapy for 70% of patients.

Double guidewire endoscopic technique, a major evolution in endoscopic retrograde cholangiopancreatography: Results of a retrospective study with historical controls comparing two therapeutic sequential strategies.

BACKGROUND AND AIM: Endoscopic access to the common bile duct (CBD) remains difficult in 10% of cases, requiring alternative techniques .CBD access was difficult after either five unsuccessful attempts, five unintentional insertions into the pancreatic duct or >10-min-long unsuccessful attempts. This retrospective study with historical controls aimed to evaluate the benefit of the double guidewire (DGW) technique after failure of standard CBD cannulation. METHODS: From January 2012 to December 2014, all patients requiring therapeutic endoscopic retrograde cholangiopancreatography (ERCP) with difficult access to CBD were included in a Studied group. This group was compared to a historical ERCP control group from January 2009 to December 2011. In the Studied group, a sequential strategy including DGW technique was done when the guidewire was unintentionally passed into the pancreatic duct. In the control group, only pre-cut technique was used. RESULTS: Among the 538 patients with naive papilla eligible for ERCP, 73 had difficult CBD access. Successful CBD access rate was higher in the Studied group: 91% (50/55) versus 67% (12/18) P = 0.0215. Complication rates were similar in both groups: 28% versus 20%, P = 0.5207. LOS was shorter in the Studied group (9.2 ± 8.5 vs 14.4 ± 7.4 days, P = 0.0028). Post-ERCP cholangitis were lower in the Studied group: 2% (1/55) versus 22% (4/18), P = 0.0118. CONCLUSION: After standard cannulation failure, DGW technique increased successful CBD access rate and decreased LOS without increasing complications.

Temporary placement of fully covered self-expandable metal stents for the treatment of benign biliary strictures.

BACKGROUND: Endoscopic treatment of benign biliary strictures (BBS) can be challenging. OBJECTIVE: To evaluate the efficacy of fully covered self-expandable metal stents (FCSEMS) in BBS. METHODS: Ninety-two consecutive patients with BBS (chronic pancreatitis (n = 42), anastomotic after liver transplantation (n = 36), and post biliary surgical procedure (n = 14)) were included. FCSEMS were placed across strictures for 6 months before endoscopic extraction. Early success rate was defined as the absence of biliary stricture or as a minimal residual anomaly on post-stent removal endoscopic retrograde cholangiopancreatography (ERCP). Secondary outcomes were the final success and stricture recurrence rates as well as procedure-related morbidity. RESULTS: Stenting was successful in all patients. Stenting associated complications were minor and occurred in 22 (23.9%) patients. Migration occurred in 23 (25%) patients. Stent extraction was successful in all but two patients with proximal stent migration. ERCP after the 6 months stenting showed an early success in 84.9% patients (chronic pancreatitis patients: 94.7%, liver transplant: 87.9%, post-surgical: 61.5%) (p = 0.01). Final success was observed in 57/73 (78.1%) patients with a median follow-up of 12 ± 3.56 months. Recurrence of biliary stricture occurred in 16/73 (21.9%) patients. CONCLUSIONS: FCSEMS placement is efficient for patients with BBS, in particular for chronic pancreatitis patients. Stent extraction after 6 months indwelling, although generally feasible, may fail in a few cases.

Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers.

Pancreatic cancer (PC) is a devastating disease progressing asymptomatically until death within months after diagnosis. Defining at-risk populations should promote its earlier diagnosis and hence also avoid its development. Considering the known involvement in pancreatic disease of exon 11 of the bile salt-dependent lipase (BSDL) gene that encodes variable number of tandem repeat (VNTR) sequences, we hypothesized upon the existence of a genetic link between predisposition to PC and mutations in VNTR loci. To test this, BSDL VNTR were amplified by touchdown-PCR performed on genomic DNA extracted from cancer tissue or blood samples from a French patient cohort and amplicons were Sanger sequenced. A robust method using probes for droplet digital (dd)-PCR was designed to discriminate the C/C major from C/T or T/T minor genotypes. We report that the c.1719C > T transition (SNP rs488087) present in BSDL VNTR may be a useful marker for defining a population at risk of developing PC (occurrence: 63.90% in the PC versus 27.30% in the control group). The odds ratio of 4.7 for the T allele was larger than those already determined for other SNPs suspected to be predictive of PC. Further studies on tumor pancreatic tissue suggested that a germline T allele may favor Kras G12R/G12D somatic mutations which represent negative prognostic factors associated with reduced survival. We propose that the detection of the T allele in rs488087 SNP should lead to an in-depth follow-up of patients in whom an association with other potential risk factors of pancreatic cancer may be present.

Real-life conditions of use of sodium phosphate tablets for colon cleansing before colonoscopy.

BACKGROUND AND STUDY AIMS: The purpose of this study was to describe the real-life conditions of use, efficacy, safety, and acceptability of sodium phosphate (NaP) tablets for colon cleansing in routine medical practice in France. PATIENTS AND METHODS: A total of 996 patients undergoing bowel preparation were enrolled by 108 gastroenterologists in this observational, longitudinal, prospective, multicenter study. The conditions of use of NaP tablets were assessed with a composite endpoint, which included six criteria for patient compliance with the recommended administration scheme and a criterion for the absence of contraindications to NaP use. RESULTS: Adequate use of NaP was reported for 75.1 % of the patients. The main reasons for misuse were a smaller fluid intake than expected with a dose of 4 tablets and noncompliance with age-related contraindications. The quality of cleansing was satisfactory: the Boston Bowel Preparation Scale (BBPS) total score was 7 or higher in 75.4 % of the patients. Gastroscopy associated with colonoscopy in 38.9 % of the patients revealed gastric lesions, which were considered as possibly related to the use of NaP tablets in 10.3 % of them. Vomiting occurred in 9.8 % of the patients, and 0.6 % discontinued bowel preparation after an adverse event. No electrolyte disorders or renal impairment was reported, even if not systematically sought. The acceptability of the NaP tablets was high, particularly among patients who previously had undergone other methods of bowel preparation. CONCLUSIONS: Despite being defined according to strict criteria, adequate use of NaP tablets was observed in a high percentage of patients. The quality of colon cleansing and the safety and acceptability of NaP tablets were satisfactory and consistent with data from randomized clinical studies.

Yarrowia lipolytica Lipase 2 Is Stable and Highly Active in Test Meals and Increases Fat Absorption in an Animal Model of Pancreatic Exocrine Insufficiency.

BACKGROUND & AIMS: Pancreatic exocrine insufficiency (PEI) reduces pancreatic secretion of digestive enzymes, including lipases. Oral pancreatic enzyme replacement therapy (PERT) with pancreatin produces unsatisfactory results. The lipase 2 produced by the yeast Yarrowia lipolytica (YLLIP2; GenBank: AJ012632) might be used in PERT. We investigated its ability to digest triglycerides in a test meal and its efficacy in reducing fecal fat in an animal model of PEI. METHODS: YLLIP2 was produced by genetically engineered Y lipolytica and purified from culture media. YLLIP2 or other gastric (LIPF) and pancreatic (PNLIPD) lipases were added to a meal paste containing dietary triglycerides, at a range of pH values (pH 2-7), with and without pepsin or human bile and incubated at 37°C. We collected samples at various time points and measured lipase activities and stabilities. To create an animal model of PEI, steatorrhea was induced by embolization of the exocrine pancreas gland and pancreatic duct ligation in minipigs. The animals were given YLLIP2 (1, 4, 8, 40, or 80 mg/d) or pancreatin (100,000 US Pharmacopeia lipase units/d, controls) for 9 days. We then collected stool samples, measured fat levels, and calculated coefficient of fat absorption (CFA) values. RESULTS: YLLIP2 was highly stable and poorly degraded by pepsin, and had the highest activity of all lipases tested on meal triglyceride at pH 4-7 (pH 6 with bile: 94 ± 34 U/mg; pH 4 without bile: 43 ± 13 U/mg). Only gastric lipase was active and stable at pH 3, whereas YLLIP2 was sensitive to pepsin hydrolysis after pH inactivation. From in vitro test meal experiments, the lipase activity of YLLIP2 (10 mg) was estimated to be equivalent to that of pancreatin (1200 mg; 100,000 US Pharmacopeia units) at pH 6. In PEI minipigs, CFA values increased from 60.1% ± 9.3% before surgery to 90.5% ± 3.2% after administration of 1200 mg pancreatin (P < .05); CFA values increased to a range of 84.6% ± 3.0% to 90.0% ± 3.8% after administration of 4-80 mg YLLIP2 (P < .05). CONCLUSIONS: The yeast lipase YLLIP2 is stable and has high levels of activity against test meal triglycerides in a large pH range, with and without bile. Oral administration of milligram amounts of YLLIP2 significantly increased CFA values, similar to that of 1.2 g pancreatin, in a minipig model of PEI.

A Metagenomic Investigation of the Duodenal Microbiota Reveals Links with Obesity.

BACKGROUND: Few studies have tested the small intestine microbiota in humans, where most nutrient digestion and absorption occur. Here, our objective was to examine the duodenal microbiota between obese and normal volunteers using metagenomic techniques. METHODOLOGY/PRINCIPAL FINDINGS: We tested duodenal samples from five obese and five normal volunteers using 16S rDNA V6 pyrosequencing and Illumina MiSeq deep sequencing. The predominant phyla of the duodenal microbiota were Firmicutes and Actinobacteria, whereas Bacteroidetes were absent. Obese individuals had a significant increase in anaerobic genera (p < 0.001) and a higher abundance of genes encoding Acyl-CoA dehydrogenase (p = 0.0018) compared to the control group. Obese individuals also had a reduced abundance of genes encoding sucrose phosphorylase (p = 0.015) and 1,4-alpha-glucan branching enzyme (p = 0.05). Normal weight people had significantly increased FabK (p = 0.027), and the glycerophospholipid metabolism pathway revealed the presence of phospholipase A1 only in the control group (p = 0.05). CONCLUSIONS/SIGNIFICANCE: The duodenal microbiota of obese individuals exhibit alterations in the fatty acid and sucrose breakdown pathways, probably induced by diet imbalance.

Factors related to bowel cleansing failure before colonoscopy: Results of the PACOME study.

BACKGROUND: The factors associated with inadequate bowel cleansing leading to colonoscopy failure are not well known. OBJECTIVE: We conducted a multicentre, prospective, observational case-control study in order to identify these factors. METHODS: Investigators included one patient with colonoscopy failure due to inadequate bowel cleansing (failure group) and the following patient with complete colonoscopy (success group). Data related to demographics, medical history, and preparation were collected and compared. Factors associated with bowel cleansing failure were identified by multivariate logistical regression analysis. RESULTS: A total of 101 gastroenterologists included 202 patients from 1 November 2009 to 15 January 2010. There was no difference between both groups with regards to baseline characteristics. In univariate analysis, factors significantly associated with bowel cleansing failure were vomiting during preparation (p = 0.0007), incomplete intake of the preparation (p = 0.002), and constipation (p = 0.02). Type and timing of preparation were not significantly different between groups. In multivariate analysis, incomplete intake of the preparation (OR 4.5, 95% CI 1.2-17.3), constipation (OR 4.2, 95% CI 1.2-14.9), and treatment with neuroleptics or antidepressants (OR 9.9 (95% CI 1.4-71.0) were independent predictors of colonoscopy failure. CONCLUSIONS: Factors associated with bowel cleansing failure were incomplete intake of the preparation, constipation, and treatment with psychotropic drugs. Interventions to reduce poor colonoscopy preparations should be targeted at these at-risk patients.

Endoscopic papillectomy for early ampullary tumors: long-term results from a large multicenter prospective study.

BACKGROUND AND STUDY AIMS: Endoscopic papillectomy of early tumors of the ampulla of Vater is an alternative to surgery. This large prospective multicenter study was aimed at evaluating the long-term results of endoscopic papillectomy. PATIENTS AND METHODS: Between September 2003 and January 2006, 10 centers included all patients referred for endoscopic papillectomy and meeting the inclusion criteria: biopsies showing at least adenoma, a uT1N0 lesion without intraductal involvement at endoscopic ultrasound (EUS), and no previous treatment. A standardized endoscopic papillectomy was done, with endoscopic monitoring with biopsies 4 - 8 weeks later where complications were recorded and complementary resection performed when necessary. Follow-up with duodenoscopy, biopsies, and EUS was done at 6, 12, 18, 24 and 36 months. Therapeutic success was defined as complete resection (no residual tumor found at early monitoring) without duodenal submucosal invasion in the resection specimen in the case of adenocarcinoma and without relapse during follow-up. RESULTS: 93 patients were enrolled. Mortality was 0.9 % and morbidity 35 %, including pancreatitis in 20 %, bleeding 10 %, biliary complications 7 %, perforation 3.6 %, and papillary stenosis in 1.8 %. Adenoma was not confirmed in the resection specimen in 14 patients who were therefore excluded. Initial treatment was insufficient in 9 cases (8 carcinoma with submucosal invasion; 1 persistence of adenoma). During follow-up, 5 patients had tumor recurrence and 7 died from unrelated diseases without recurrence. Finally, 81.0 % of patients were cured (95 % confidence interval 72.3 % - 89.7 %). CONCLUSION: Endoscopic papillectomy of selected ampullary tumors is curative in 81.0 % of cases. It must be considered to be the first-line treatment for early tumors of the ampulla of Vater without intraductal invasion.

Factors associated with adenoma detection rate and diagnosis of polyps and colorectal cancer during colonoscopy in France: results of a prospective, nationwide survey.

INTRODUCTION: Colonoscopy can prevent deaths due to colorectal cancer (CRC) through early diagnosis or resection of colonic adenomas. We conducted a prospective, nationwide study on colonoscopy practice in France. METHODS: An online questionnaire was administered to 2,600 French gastroenterologists. Data from all consecutive colonoscopies performed during one week were collected. A statistical extrapolation of the results to a whole year was performed, and factors potentially associated with the adenoma detection rate (ADR) or the diagnosis of polyps or cancer were assessed. RESULTS: A total of 342 gastroenterologists, representative of the overall population of French gastroenterologists, provided data on 3,266 colonoscopies, corresponding to 1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and 38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001), personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001, respectively), and positive fecal occult blood test (p=0.0005). The prevalence of CRC was three times higher in patients with their first colonoscopy (4.2% vs. 1.4%; p<0.0001). CONCLUSIONS: For the first time in France, we report nationwide prospective data on colonoscopy practice, including histological results. We found an average ADR of 17.7%, and observed reduced CRC incidence in patients with previous colonoscopy.

Major bile duct injuries during cholecystectomy in children: conservative laparoscopic approach is possible.

Major bile duct injury is an inherent complication in cases of both open and laparoscopic cholecystectomies. In case of choledochal lesion, conservative treatment or internal derivation by a Roux-en-Y can be proposed. We report the case of a 5-year-old boy referred to our center for an iatrogenic choledochal ligation after open cholecystectomy (performed 20 d before) for asymptomatic gallbladder stone. We performed a laparoscopic conservative treatment with a consistent good result 5 years after the procedure.

Treatment of malignant gastroduodenal obstruction with a nitinol self-expanding metal stent: an international prospective multicentre registry.

BACKGROUND: Duodenal stenting has become a broadly accepted first line of treatment for patients with advanced malignant gastroduodenal obstruction as these patients are difficult to treat and are poor surgical candidates. AIMS: To document duodenal stent performance for palliative management of malignant gastroduodenal obstruction. METHODS: Multicentre, single arm, prospective registry documenting peroral endoscopic duodenal stenting procedures in 202 patients. RESULTS: Technical success achieved in 98% (CI, 95%, 99%) of stent placements. Increase of Gastric Outlet Obstruction Score by at least 1 point compared to baseline was achieved in 91% (CI, 86%, 95%) of patients persisting for a median of 184 days (CI, 109, 266). By day 5 (CI, 4, 6) after stent placement, 50% of patients experienced a score increase of at least 1 point. Improvement from 14% of patients at baseline tolerating soft solids or low residue/normal diet to 84% at 15 days, 86% at 30 days, 81% at 90 days, 79% at 180 days, and 70% at 270 days. Complications included stent ingrowth and/or overgrowth (12.4%), transient periprocedural symptoms (3%), bleeding (3%), stent migration (1.5%), and perforation (0.5%). CONCLUSIONS: Safety and effectiveness of duodenal stenting for palliation of malignant gastroduodenal obstruction was confirmed in the largest international prospective series to date.

Adefovir combined with hepatitis C virus treatment may prevent hepatitis B reactivation after hepatitis C virus eradication in hepatitis B and C virus carriers.

This observation reports that a hepatitis B virus (HBV) reactivation, as the result of hepatitis C virus (HCV) eradication on a dominant HCV coinfected HBV/HCV patient, was subsequently prevented by treating both viral infections together. This finding raises the question as to whether preemptive HBV treatment should be prescribed along with HCV treatment to prevent HBV from being reactive after HCV eradication in coinfected HBV/HCV patients.

Further biochemical characterization of human pancreatic lipase-related protein 2 expressed in yeast cells.

Recombinant human pancreatic lipase-related protein 2 (rHPLRP2) was produced in the protease A-deficient yeast Pichia pastoris. A major protein with a molecular mass of 50 kDa was purified from the culture medium using SP-Sepharose and Mono Q chromatography. The protein was found to be highly sensitive to the proteolytic cleavage of a peptide bond in the lid domain. The proteolytic cleavage process occurring in the lid affected both the lipase and phospholipase activities of rHPLRP2. The substrate specificity of the nonproteolyzed rHPLRP2 was investigated using pH-stat and monomolecular film techniques and various substrates (glycerides, phospholipids, and galactolipids). All of the enzyme activities were maximum at alkaline pH values and decreased in the pH 5-7 range corresponding to the physiological conditions occurring in the duodenum. rHPLRP2 was found to act preferentially on substrates forming small aggregates in solution (monoglycerides, egg phosphatidylcholine, and galactolipids) rather than on emulsified substrates such as triolein and diolein. The activity of rHPLRP2 on monogalactosyldiglyceride and digalactosyldiglyceride monomolecular films was determined and compared with that of guinea pig pancreatic lipase-related protein 2, which shows a large deletion in the lid domain. The presence of a full-length lid domain in rHPLRP2 makes it possible for enzyme activity to occur at higher surface pressures. The finding that the inhibition of nonproteolyzed rHPLRP2 by tetrahydrolipstatin and diethyl-p-nitrophenyl phosphate does not involve any bile salt requirements suggests that the rHPLRP2 lid adopts an open conformation in aqueous media.