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Peroralcholangio-pancreatoscopy (POCP) is used for diagnosis and treatment of biliopancreatic disease when standard endoscopy (ERCP) or pre-operative imaging workup failed. We aimed to evaluate the diagnostic and therapeutic performance of POCP in complex biliary and pancreatic diseases.Patients with indeterminate biliary or pancreatic duct (PD) strictures, and patients with failure of complex biliary or pancreatic stones removal, were enrolled (six centers). The primary endpoint evaluated malignancy diagnostic performances (accuracy, sensitivity, specificity) and therapeutic performances (biliary or pancreatic stones extraction). Secondary endpoints evaluated: technical success in lesion visualization, ease of maneuvering, image quality and 30-days complications.From November 2016 to March 2018, 66 patients were included: 29/37 women/men, median age (IQR): 73 (64-82). Fifty-three patients had diagnostic POCP and 13 patients therapeutic POCP. One endoscopist with one or two endoscopy nurses performed 94% of the POCP. The 'POCP visual impression' of malignancy showed 92.0% sensitivity, 92.9 % specificity and 92.5 % overall accuracy compared with the final diagnosis. 'POCP-guided samples histological analysis' showed 75.0 % sensitivity and 91.6% specificity. The technical success for lesion visualization was 98.5%. The median VAS scores for insertions in bile and PD were respectively 9.0 (8.1-9.6) and 9.0 (8.8-10.0). Median VAS score for access to the lesion and image quality were respectively 9.0 (7.7-9.6) and 9.0 (7.9-9.7). Only three 30-day minor complications occurred without any major complications.POCP was an effective, safe and easy-to-use tool in routine clinical practice for the management of complex diagnostic and therapeutic biliary and pancreatic diseases (NCT03190343).

To describe the working conditions during pregnancy of medical residents. To describe adverse outcomes and to identify professional factors associated with these outcomes.This observational study described the working conditions during pregnancy of medical residents and the outcomes. An online questionnaire was sent to the 773 residents, of all specialties, enrolled in medical school in Nancy, France.Three hundred and one residents participated in the study (38,9 %). The average daily working time of students was closed to 9hours, regardless the trimester, with a break time that rarely exceed one hour. Residents said continued to be on call beyond 10 weeks of gestation in 87.5 % of cases, the legal term for stopping these. The rate of adverse outcomes was 42.6 % (23/54). The rates of preterm labors and preterm births were 22.5 % and 15 % respectively. A significant association was found between working more than 10hours per day during 2nd trimester and adverse outcomes.A strengthening of health monitoring at work with adaptation of workstation, information campaigns, as well as the designation of resource persons within the faculties seem essential.

BACKGROUND: DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanced neoplasia. Several studies recently demonstrated the ability of next-generation sequencing (NGS) analysis to detect DNA mutations in pancreatic CF, but few studies have performed a systematic comparative analysis between pancreatic CF and neoplastic surgical tissue (NT). The value of CF-NGS analysis indicators for determining surgical resection necessitates evaluation. AIM: To confirm whether CF genomic profiles are a reliable malignancy predictor by comparing NGS mutational analyses of CF and NT. METHODS: Patients requiring surgery for high-risk pancreatic cysts were included in a multicenter prospective pilot study. DNA from CF (collected by endoscopic ultrasound-guided fine needle aspiration (known as EUS-FNA)) and NT (collected by surgery) were analyzed by NGS. The primary objective was to compare the mutation profiles of paired DNA samples. The secondary objective was to correlate the presence of specific mutations (KRAS/GNAS, RAF/ PTPRD/CTNNB1/RNF43/POLD1/TP53) with a final cancer diagnosis. Sensitivity and specificity were also evaluated. RESULTS: Between December 2016 and October 2017, 20 patients were included in this pilot study. Surgery was delayed for 3 patients. Concordant CF-NT genotypes were found in 15/17 paired DNA, with a higher proportion of mutated alleles in CF than in NT. NGS was possible for all pancreatic CF collected by EUS-FNA. In 2 cases, the presence of a KRAS/GNAS mutation was discordant between CF and NT. No mutations were found in 3 patients with NT or pancreatic cysts with high-grade dysplasia. The sensitivity and specificity of KRAS/GNAS mutations in CF to predict an appropriate indication for surgical resection were 0.78 and 0.62, respectively. The sensitivity and specificity of RAF/PTPRD/CTNNB1 /RNF43/POLD1/TP53 mutations in CF were 0.55 and 1.0, respectively. CONCLUSION: Mutational analyses of CF and NT were highly concordant, confirming the value of NGS analysis of CF in the preoperative malignancy assessment. However, these results need to be confirmed on a larger scale.

Background The aim of this prospective multicenter study was to compare a flexible 19 G needle with nitinol shaft (19 G Flex) with a standard 22 G needle for transduodenal endoscopic ultrasound (EUS)-guided sampling of pancreatic head tumors. Methods Patients with pancreatic head tumors requiring tissue diagnosis were randomized into two arms: puncture with either a 19 G Flex needle or a 22 G needle. The primary end point was diagnostic accuracy for malignancy. The secondary end points were ergonomic scores, sample cytohistological quality, and complications. A 6-month follow-up was performed. Results 125 patients were randomized and 122 were analyzed: 59 patients in the 19 G Flex arm and 63 patients in the 22 G arm. The final diagnosis was malignancy in 111 patients and benign condition in 11. In intention-to-treat analysis, the diagnostic accuracy for malignancy of the 19 G Flex and 22 G needles was 69.5 % (95 % confidence interval [CI] 56.1 % – 80.8 %) vs. 87.3 % (95 %CI 76.5 % – 94.4 %), respectively (P = 0.02). In per-protocol analysis excluding eight technical failures in the 19 G Flex group, the diagnostic accuracy of the 19 G Flex and 22 G needles was not statistically different: 80.4 % (95 %CI 66.9 % – 90.2 %) vs. 87.3 % (95 %CI 76.5 % – 94.4 %; P = 0.12). Technical success was higher in the 22 G arm than in the 19 G Flex arm: 100 % (95 %CI 94.3 % – 100 %) vs. 86.4 % (95 %CI 75.0 % – 94.0 %), respectively (P = 0.003). Transduodenal EUS-guided sampling was more difficult with the 19 G Flex (odds ratio 0.68, 95 %CI 0.47 – 0.97). Conclusion The 19 G Flex needle was inferior to a standard 22 G needle in diagnosing pancreatic head cancer and more difficult to use in the transduodenal approach.

Background Endoscopic access to common bile duct (CBD) remains difficult in 10% of cases, requiring alternative techniques. This retrospective study with historical controls aimed to evaluate the benefit of the double guidewire (DGW) technique as part of a standardized protocol in CBD access, after failure of standard cannulation and to compare successful CBD access rates, complication rates and length of hospital stay (LOS) in two groups. Method From January 2012 to December 2014, all consecutive patients requiring therapeutic endoscopic retrograde cholangiopancreatography (ERCP) with “difficult” access to CBD were included in a “studied group”. CBD access was “difficult” after either: 5 unsuccessful attempts, 5 unintentional insertions in the pancreatic duct or more than 10-minute-long unsuccessful attempts. This group was compared to a historical control group undergoing ERCP from January 2009 to December 2011. In the studied group, a sequential strategy including DGW technique was performed when the guidewire was unintentional passed into the pancreatic duct. In the control group, only precut 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) vs 67%(12/18) p=0.0215. Complication rates were similar in both groups: 28% vs 20%, p=0.5207. LOS was shorter in the studied group (9.2±8.5 days vs. 14.4±7.4 days, p=0.0028). Post-ERCP cholangitis were lower in the study group: 2%(1/55) vs 22%(4/18), p = 0.0118. Conclusion After standard cannulation failure, DGW technique increased successful CBD access rate and decreased LOS without increasing complications. This article is protected by copyright. All rights reserved.

Noninvasive indexes have been developed to predict fibrosis staging. The aim of this study was to assess the diagnostic accuracy of these indexes in comparison with liver histology in hepatitis C virus (HCV)-infected patients. A total of 235 consecutive patients with HCV infection from the Fibropaca multicentre independent study were included in this paper. FibroTest (FT), aspartate aminotransferase to platelet ratio index (APRI) and Forns score were assessed in the cohort and compared with liver histology performed on the same day. The main end point was the area under characteristic curves (AUCs) for the diagnosis of significant fibrosis (F2-F4) and cirrhosis (F4) by the METAVIR classification. Mean age was 46 (+/-11) years, 55% were males, 42% (n = 99) had significant fibrosis (F2-F4) and 7% (n = 16) had cirrhosis (F4). For the diagnosis of significant fibrosis, respective AUCs of FT, APRI and Forns score were 0.81 (95% confidence interval: 0.76-0.86), 0.71 (0.67-0.79) and 0.76 (0.70-0.82); for cirrhosis prognosis, AUCs of FT and APRI were 0.82 (0.77-0.87) and 0.81 (0.76-0.86) (AUCs not significantly different). Using each index independently, all patients were classified by FT, 214 (91%) patients were classified by APRI and 129 (55%) by Forns score. There were significantly more cases of discordances between APRI and liver biopsy than between FT or Forns score and liver biopsy (P < 0.05). Performing all scores (FT, Forns and APRI) without liver biopsy allowed fibrosis to be well evaluated in 191 patients (81.3%), including patients with FT failure. Liver biopsy remained mandatory to evaluate fibrosis in 44 patients (18.7%). Our study shows that performing all the tests and liver biopsy improves the diagnostic accuracy for liver fibrosis in chronic hepatitis C patients without patent comorbidities. The combination of all tests with liver biopsy allowed 225/235 (96%) patients to be correctly classified. The combination of all tests without liver biopsy allowed 191/235 (81.3%) patients to be correctly classified; liver biopsy remained mandatory in some patients (18.7%).

The standard of care (SOC) for the treatment of HCV genotype 2 (HCV-2) was pegylated interferon alpha plus ribavirin (PEG-IFN/RBV) at weight-based doses for a response-guided duration. The launches of sofosbuvir and daclatasvir in 2014 have resulted in new, better tolerated and shorter treatment. The combination of sofosbuvir and RBV for 12 weeks appears to be the new SOC in both European and American guidelines. The cost and therefore the access to this treatment remains a problem in many countries because of major economic constraints. For the few more difficult-to-treat patients, a combination of direct acting antivirals may be suitable and is being studied in ongoing trials. Because of rapidly changing treatment recommendations, the decision to treat HCV-2 patients with currently approved drugs or to wait until a better option is available in the future, must be made according to the stage of fibrosis.

Off-label prescribing matches the using of medications outside the summary of product characteristics. Adverse drug reactions are often poorly studied in off-label situations, which may expose patients to additional safety risks, and impose taking specific precautions. The current off-label prescribing practice of baclofen for alcohol-dependence in France is a typical illustration of such a situation. CAMTEA is a regional system set up in 2010 in Northern France, which gathers addiction and pharmacovigilance specialists, and aims at strengthening the prescription supervising and the monitoring of some off-label medication used for addictive disorders, especially baclofen. Until now, institution or office-based pharmacists have not been implicated, whereas they engaged their liability when delivering off-labeled treatment and they may highly contribute to the patient monitoring and the spotting of adverse events. We propose hereby possible measures for involving pharmacists into the patient supervising system developed within CAMTEA. In the current French context concerning the off-label use of baclofen, which will be the first off-label prescribing practice to be framed by a new legal disposition called "temporary use recommendation", the key role of pharmacists should be highlighted.

Worldwide, 50-70 million subjects are infected with an hepatitis C virus (HCV) genotype 2, 3, 4, 5 or 6. In these patients, the combination of PEG-INF-α and ribavirin remains the currently approved standard-of-care treatment. The identification of different potential therapeutic targets in the HCV life cycle has led to the development of both direct antiviral agents (DAAs) and reagents targeting host functions essential for viral replication. DAAs comprise so far first-generation, second-wave and second-generation NS3/4A protease inhibitors (PIs), nucleos(t)ide (NIs) and non-nucleoside inhibitors of the NS5B RNA polymerase and NS5A complex inhibitors. The main host-protein-directed antiviral agents are cyclophilin inhibitors and silibinin. Whereas the launch of first-generation PIs was a major landmark in the management of genotype 1 (GT-1)-infected patients, these drugs are inactive in most non-GT-1-infected patients. Several of these and other drugs have now reached phase II and even phase III clinical stage development. The purpose of this article is to provide an overview of the clinical results recently reported for the treatment for non-GT-1 HCV infection with a focus on the most promising new compounds and combinations.

Summary Background Non-invasive liver fibrosis scores such as Hepascore (HS) have been proposed as an alternative to liver biopsy in hepatitis C virus (HCV)-infected patients. Aim To validate HS as an alternative to liver biopsy and Fibrotest (FT) and propose five optimized combination algorithms to improve diagnostic accuracy. Methods The cohort included 467 patients with HCV. There were 274/467 (59%) men, and mean age was 47 ± 12 years. Results Hepascore area under ROC curves (AUC) for ≥F2, F3F4 and F4 diagnosis were 0.82, 0.84 and 0.90 respectively, in the same range as FT. HS and FT were concordant in 387/467 (82%) for fibrosis staging. Among these patients, 342/387 (88%) were concordant with liver biopsy. AUCs of aspartate aminotransferase (AST) to Platelets Ratio Index (APRI) and Forns for ≥F2 were 0.76 and 0.73 (0.65–0.79) respectively. The algorithm combining APRI and HS had the highest rate of avoided liver biopsies (45%) with a high diagnostic accuracy (91%). Conclusions Hepascore is an accurate non-invasive marker for ≥F2 and F4 diagnosis in HCV patients. In a pragmatic approach, a stepwise optimized algorithm combining APRI and FT or HS considerably increases diagnostic accuracy and avoided liver biopsies.

Hepatitis C virus (HCV) genotypes are distributed differently depending on geography and route of infection. We characterized the distribution of genotypes in a large cohort of patients with chronic hepatitis C in the South-east of France and evaluated the relative prevalence according to time of acquisition. One thousand, one hundred-and-eighty-three patients who were anti-HCV-positive were studied. HCV genotype distribution has changed significantly from the 1960s to 2000. The prevalence of genotype 1b decreased from 47% before 1978 to 18.8% in the 1990s while the prevalence of genotype 1a and 3a increased during the same period from 18% and 15.3% to 28.8% and 26.3%, respectively. The logistic regression model showed that genotype 1a was significantly more common in patients infected through intravenous drug injection odds ratio ((OR): 2.08, P < 0.01) and after 1990 (OR: 1.98, P < 0.05). Genotype 1b was significantly less frequent in patients infected through intravenous drug injection (OR: 0.17, P < 0.001) and has decreased since 1978 (OR: 0.27, P < 0.001). Genotype 3a was independently associated with intravenous drug injection (OR: 6.1, P < 0.001) and tattooing (OR: 8.01, P < 0.001) and was more frequent in the 1979-90 period (OR: 2.05 and 1.74, P < 0.001 and P < 0.05). Our results show a modification of HCV genotypes distribution over the last four decades due to an increase of intravenous drug use (IVDU) contamination and an evolution of HCV genotypes distribution only in IVDU population characterized by a decrease of genotype 1b, an increase of genotype 3a from 1970 to 1990 and a higher increase of genotype 1a which is currently the predominant genotype in our population.