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ESD is the treatment of choice for superficial neoplasms of the oesophagus; ESD is oncologically efficient and associated with less morbidity than the surgical alternative. ESD requires a high level of skill, being both technically challenging and time consuming. Therefore, ESD is often reserved for experts. A combination of a tunnel technique with clip-line traction may enable optimisation of oesophageal ESD. From January 2015 to December 2016, we performed a prospective two-centre case study of consecutive “tunnel + clip” oesophageal ESD. Four young operators (each of whom had performed fewer than 50 ESDs and fewer than five oesophageal ESDs) treated patients requiring ESD using the tunnel + clip method. This involves generation of a classic tunnel beneath the lesion, with constant traction being applied by a clip with a line placed at the oral side of the tunnel. Sixty-two lesions (25 SCCs and 34 ADK/HGDs complicating Barrett’s oesophagus) were consecutively resected. The en bloc, R0, and curative resection rates were 100% (62/62), 88.7% (55/62), and 74.2% (46/62), respectively. No perforation was noted. The mean ESD velocity was 24.5 mm2/min for lesions of mean length 59.6 mm. The tunnel + clip approach greatly aided the procedure. No pathological damage caused by clipping was evident. Use of the tunnel + clip strategy to treat oesophageal ESD is effective and safe, even when performed by physicians with little prior experience. It is thus possible to standardise ESD of superficial oesophageal neoplasms and increase the velocity of dissection. Our procedure will encourage the use of oesophageal ESD in Western countries.

Background & Aims Renal toxicity of first generation protease inhibitors (PIs) was not a safety signal in phase III clinical trials, but was recently reported in recent studies. It appeared important to determine the clinical significance of these findings. Methods We retrospectively analysed 101 HCV patients receiving triple therapy with telaprevir (n = 36) or boceprevir (n = 26) or double therapy (n = 39) with peginterferon and ribavirin and having a close monitoring of eGFR (MDRD formula) during and after treatment. EGFR decline over time was assessed by a linear mixed-effects model (LMEM) with search for possible explanatory covariates. Results Patients treated with telaprevir presented a significant decrease of eGFR with the same kinetics: initial decrease at W (week) 4, nadir at W8 (mean decrease 17.0 ± 18.9 ml/min/1.73 m2) and return to baseline at W16. The W8 eGFR was correlated with the D0 eGFR (R2 = 0.49). The LMEM showed that interindividual variability in the slope of eGFR vs time between D0 and W8 was non-significant and eGFR nadir could be predicted from eGFR obtained at D0. In multivariate analysis, eGFR intercept (i.e. baseline value) was associated with older age and male sex. Conclusion The eGFR significantly varied in telaprevir group only. Our model showed that eGFR nadir mainly depended on initial eGFR. As telaprevir has been shown to inhibit mostly the drug transporter OCT2 which interacts with creatinine transport, the early decrease of eGFR observed could be a benign phenomenon. However, as unpredictable true renal toxicity may occur during therapy, we recommend a thorough follow-up of eGFR.

RésuméL’ascite, dans 20 % des cas, n’est pas liée à une cirrhose hépatique. Elle obéit alors le plus souvent à une physiopathologie différente. La compréhension de ces mécanismes physiopathologiques conduit au diagnostic étiologique. La démarche diagnostique est basée essentiellement sur la ponction et l’étude du liquide, particulièrement la concentration en protides et le gradient sérum-ascite d’albumine, qui aideront à en discriminer les grands cadres étiologiques. Dans les pays occidentaux, les pathologies tumorales et cardiaques sont dominantes, tandis que les pays en voie de développement sont concernés surtout par les pathologies infectieuses, au premier rang desquels figure la tuberculose. D’autres causes plus rares doivent être connues et constituent parfois le mode d’entrée de la maladie. Leur connaissance facilitera l’approche thérapeutique.AbstractAscites, in 20% of cases, is not linked to liver cirrhosis. The pathophysiology is most often different. The understanding of these pathophysiological mechanisms can lead to etiologic diagnosis. The diagnostic approach is mainly based on the biological study of ascites, especially protein concentration and albumin gradient between serum and ascites. In Western countries, tumors and heart diseases are the predominant causes, while developing countries are mainly concerned by infectious diseases, among which tuberculosis is the leading cause. Other uncommon causes must be recognized, as ascites may be the presenting feature of the disease. Their knowledge will facilitate the therapeutic approach.

Background Campylobacter fetus infections usually occur in immunodepressed patients or patients presenting with diabetes mellitus or cancer. They rarely cause diarrhea but frequently cause bacteremia or vascular diseases. The therapeutic management is not well codified and fluoroquinolone resistance is continuously increasing. Methods We conducted a retrospective study of C. fetus infections from January 2007 to August 2013 at the Limoges teaching hospital. The infections were defined by at least 1 bacteriological sample positive for C. fetus. Results Twenty patients were included (15 men), with an average age of 73 years (43–91). Sixteen presented with cancer, 12 with solid cancer including 9 of the urinary tract, and 9 patients with hematologic diseases. Five patients presented with diabetes mellitus, 9 with isolated bacteremia, 3 with cellulitis, and 3 with septic arthritis. The diagnosis was made by blood cultures for 17 patients. Twenty percent of the isolates were resistant to amoxicillin and 30% to fluoroquinolones. The therapeutic regimens and the treatment duration were quite different. The outcome was unfavorable for 3 patients whose implanted port had not been removed and 1 with subdural hematoma infection. 1 patient died. Conclusions C. fetus infection occurs in case of underlying diseases, most frequently promoting urinary tract cancer. Fluoroquinolones must not be used without susceptibility testing and catheters should be removed.

Patients with psychiatric disorders are usually more exposed to multiple somatic illnesses, including liver diseases. Specific links are established between psychiatric disorders and alcohol hepatitis, hepatitis B, and hepatitis C in the population as a whole, and specifically in drug abusers. Metabolic syndrome criteria, and associated steatosis or non-alcoholic steato-hepatitis (NASH) are frequent in patients with chronic psychiatric disorders under psychotropic drugs, and should be screened. Some psychiatric medications, such as neuroleptics, mood stabilizers, and a few antidepressants, are often associated with drug-induced liver injury (DILI). In patients with advanced chronic liver diseases, the prescription of some specific psychiatric treatments should be avoided. Psychiatric disorders can be a limiting factor in the decision-making and following up for liver transplantation.

We read with great interest the paper of Bahin et al comparing piecemeal endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for large colorectal laterally spreading lesions (LSLs) from a medico-economic point of view.1 Since the expanded use of ESDs in Japan that began in the early 2000s, a debate still persists in Western countries about the absolute need for en bloc resection of large colorectal lesions with a low risk of submucosal cancer.2 3 ESDs are associated with a high en bloc resection rate, low risk of recurrence and perfect pathological analysis.4 Defenders of piecemeal EMR point out the higher risk of ESD, the long duration of procedures, the discrepancies between Eastern and Western series, and the low proportion of lesions with superficial submucosal cancer.5 They also point out the good results of wide-field (WF)-EMR for complete eradication even when several sessions are needed.6 Economic reasons are not often mentioned, although they could be considered …

Introduction L’objectif etait de determiner la prevalence des plaintes abdominales chez les patients atteints de syndrome de Sjogren primitif (SSp) conformement aux criteres ACR-EULAR de 2016, et d’evaluer leur relation avec les caracteristiques de la maladie, en particulier l’activite systemique, la penibilite et le statut serologique. Patients et methodes Cent cinquante patients avec un SSp ont ete interroges sur leurs symptomes abdominaux en utilisant un score global de symptomes (GSS). L’etude a ete menee entre juillet 2017 et juin 2018 dans un centre hospitalier francais. Les donnees concernant les caracteristiques cliniques et biologiques du SSp, son activite (score ESSDAI) et sa penibilite (score ESSPRI) ont ete collectees dans le meme temps. Resultats Quatre-vingt-quinze pour cent des patients atteints de SSp presentaient des symptomes abdominaux avec un score GSS median de 9,7 ± 6,2 points sur 36. Le symptome le plus frequent etait la sensation de tension abdominale (68 %). Plus de la moitie des patients souffraient egalement d’epigastralgies (54 %), d’inconfort abdominal (58 %) et/ou de constipation (54 %). En ce qui concerne les elements du score ESSDAI, une atteinte generalisee ou du systeme nerveux central etait associe a un score GSS eleve. Il existait une correlation entre le score ESSPRI total et le score GSS (p Conclusion Cette etude a revele que plus de 90 % des patients atteints de SSp presentent des symptomes abdominaux. Il existe une correlation entre les plaintes digestives et la penibilite ressentie. Le dysfonctionnement du systeme nerveux autonome semble occuper une place importante. Au cours du SSp, des auto-anticorps diriges contre les recepteurs muscariniques pourraient expliquer la neuropathie autonome et entrainer des troubles gastro-intestinaux. La gastro paresie semble particulierement responsable des symptomes.

The occurrence of corticosteroid-induced hepatitis is a rare event that has been recently described in the literature. We report the case of an acute cytolytic hepatitis in a patient treated with methylprednisolone for multiple sclerosis associated with an autoimmune thyroid dysfunction. After ruling out other etiologies, we concluded that the acute liver injury was due to steroids, and we analyzed the specific circumstances in the literature where methylprednisolone may have been responsible for acute hepatitis.

Introduction: Gastroparesis, or delayed gastric emptying, can be diagnosed with gastric emptying scintigraphy. Manometric studies of patients with gastroparesis show increased pyloric tone (pylorospasm). Among the recent endoscopic therapies for pylorospasm is peroral endoscopic pylorotomy (POP). In this study, we explored the effect of POP on gastric emptying in healthy pigs. Material and methods: Four mini-pigs underwent POP following general anaesthesia. The mucosal entrance was situated 5 cm above the pylorus. POP was performed through a submucosal tunnel dissection. The duration of gastric emptying was assessed by scintigraphy before and after the procedure. The pigs were then euthanised for necropsy and pathologic assessment of the pylorus. Results: The mean duration of the procedure was 55 (± 4 SD) min. All surgeries were performed in their entirety with 100 % feasibility. There were no cases of bleeding. The one case of perforation had no clinical significance. The duration of gastric emptying was 2.22-fold shorter after POP compared with before POP (T½ post-POP = 84.5 [± 35.7 SD] min vs. T½ pre-POP = 188.4 [± 87.3 SD] min; P = 0.029). In agreement with the endoscopic observations, sectioning of the pyloric muscle in each pig was histologically complete. Conclusion: The efficacy of the procedure provides indirect proof of the involvement of the pyloric ring in delayed gastric emptying and suggests new therapies for patients with gastroparesis. Our protocol combining gastric emptying scintigraphy and POP validated the use of anaesthetised mini-pigs as a learning and training model for POP or other endoscopic/surgical procedures related to gastric emptying.

Before the advent of direct acting antiviral agents (DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the present era of new potent DAAs, a place is still devoted to the drug. Ribavirin associated with sofosbuvir alone is efficient in the treatment of most cases of G2 infected patients. All options currently available for the last difficult-to-treat cirrhotic G3 patients contain ribavirin. Reducing treatment duration to 12 wk in G1 or G4 cirrhotic compensated patients is feasible thanks to ribavirin. Retreating patients with acquired anti NS5A resistance-associated variants using ribavirin-based strategies could be useful. The addition of ribavirin with DAAs combinations however, leads to more frequent but mild adverse events especially in cirrhotic patients. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized even in difficult-to-treat patients: The optimization of ribavirin dosage according to an early monitoring of blood levels has been suggested to be relevant in double therapy with peginterferon or sofosbuvir but not with very potent combinations of more than two DAAs.

Background and study aims: The hemostatic powder TC-325 (Hemospray; Cook Medical, Winston-Salem, North Carolina, USA) has shown promising results in the treatment of upper gastrointestinal bleeding (UGIB) in expert centers in pilot studies. The aim of this study was to evaluate the feasibility and efficacy of TC-325 in a large prospective registry of use in routine practice. Patients and methods: The data of all patients treated with TC-325 were prospectively collected through a national registry. Outcomes were the immediate feasibility and efficacy of TC-325 application, as well as the rates of rebleeding at Day 8 and Day 30. Multivariate analysis was performed to determine predictive factors of rebleeding. Results: A total of 202 patients were enrolled and 64 endoscopists participated from 20 centers. TC-325 was used as salvage therapy in 108 patients (53.5 %). The etiology of bleeding was an ulcer in 75 patients (37.1 %), tumor in 61 (30.2 %), postendoscopic therapy in 35 (17.3 %), or other in 31 (15.3 %). Application of the hemostatic powder was found to be very easy or easy in 31.7 % and 55.4 %, respectively. The immediate efficacy rate was 96.5 %. Recurrence of UGIB was noted at Day 8 and Day 30 in 26.7 % and 33.5 %, respectively. Predictive factors of recurrence at Day 8 were melena at initial presentation and use of TC-325 as salvage therapy. Conclusion: These multicenter data confirmed the high rate of immediate hemostasis, excellent feasibility, and good safety profile of TC-325, which could become the treatment of choice in bleeding tumors or postendoscopic bleeding but not in bleeding ulcers where randomized studies are needed. Trial registration: ClinicalTrials.gov (NCT02595853)

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Nous rapportons la seconde description endoscopique d’infection a Listeria mocoytogenes, chez un patient de 30 ans suivi pour une rectocolite hemorragique et traite par azathioprine. L’endoscopie montrait la presence d’ulcerations aphtoides. L’evolution fut favorable avec une antibiotherapie adaptee. Il s’agit d’une complication infectieuse rare mais devant etre connue des patients porteurs deMICI et traites par immunosuppresseurs, notamment l’azathioprine.

Background & Aims Hepatitis C virus-related B-cell proliferation is a model of virus-driven autoimmune/neoplastic disorder leading to mixed cryoglobulinaemia and/or B-cell non-Hodgkin lymphoma. These lymphomas are often marginal zone lymphomas or diffuse large B-cell lymphomas. Peginterferon/Ribavirin therapy has proved its crucial role in the cure of these non-Hodgkin lymphomas, but data are lacking concerning new direct anti-viral agents. Methods We report five cases of Hepatitis C virus-associated B-cell non-Hodgkin lymphoma treated with direct anti-viral agents: two marginal zone lymphomas received direct anti-viral agents alone (one with a leukaemic phase only, one with splenic and deep lymph nodes localizations); one renal marginal zone lymphoma with renal insufficiency received direct anti-viral agents and four rituximab infusions simultaneously; two diffuse large B-cell lymphomas were treated with direct ant-viral agents following chemotherapy. Results Sustained virological response was obtained in all patients, and complete remission of NHL was noted 6 months after cessation of any treatment except for one patient with a persistent small leukaemic phase. Conclusion Direct anti-viral agents might be proposed as a first-line treatment in marginal zone lymphomas in the case of no life-threatening complications with the precaution of a long-term follow-up. In the setting of diffuse large B-cell lymphomas, well-tolerated direct anti-viral agents could potentially be introduced very early not only to prevent relapse of these lymphomas but also to limit the liver toxicity of chemotherapy and rituximab by preventing outbreaks of viral load. New observations and trials should support these assumptions.

Endoscopic submucosal dissection (ESD) is the treatment of choice for superficial gastrointestinal neoplasms but is technically very difficult, challenging, and timeconsuming. It should only be performed by experts. Good exposure of the submucosal layer is key in terms of procedural efficiency and safety [1]. Many have sought to optimize exposure of the submucosal layer using countertraction [2], creation of a pocket, or by tunneling beneath the lesion [3,4]. The mucosal incision is performed blind at the beginning of the procedure and can be very challenging. Indeed, an incision that is too deep carries the risk of perforation, but one that is too superficial slows the procedure considerably because persisting submucosal or mucosal fibers grip the lesion, making it very difficult to position the tip of the scope beneath the lesion. In addition, bleeding is common during this step because the submucosal vessels cannot be identified beforehand. This phase is particularly challenging for physicians at the beginning of their learning curves, and when the lesion lies in front of and perpendicular to the scope – a tangential position being ideal. We report a new way in which to facilitate exposure of the submucosal layer at the commencement of a colorectal ESD. After marking around the lesion, we perform mucosectomy of the normal mucosa surrounding the lesion using a 10-mm stiff snare (Olympus, Japan) and endocut current. Several contiguous mucosectomies are performed outside the marks. This allows immediate exposure of the submucosal space without any bleeding (● " Fig.1; ● " Video 1) and direct exposure of the submucosal vessels, which can now be immediately and prophylactically coagulated. Next, a pocket is easily and safely created with constant good exposure of the submucosal fibers. The mucosal incision is easily enlarged, with minimal (dangerous) blind dissection and more accurate knife positioning because the mucosal incision is relatively deep. This new “tip” may be helpful, particularly when a colonic ESD is difficult, or when the physician is inexperienced.

As the world's population becomes older, the burden of hepatitis B virus in elderly has to be considered. The liver changes with aging and its function is eventually altered. The prevalence of hepatitis B virus is paradoxically more important in elderly in areas having vaccination programs, because of a loosening of the prevention in older patients. Some differences in hepatitis B presentation must be enhanced in elderly: lower spontaneous hepatitis B surface antigen clearance after a recent contamination, major risk of cirrhosis and hepatocarcinoma. Acute hepatitis B seems to be more often symptomatic, with a great risk of chronicity. Hepatocarcinoma linked to hepatitis B virus has a higher prevalence and a different presentation in elderly. Its treatment is the same as in younger people but is less often possible. Liver transplantation is contraindicated after 70 years old. Hepatitis B treatment panel is the same as in younger people (pegylated interferon, nucleoside or nucleotide agents). It gives identical results with no particular adverse events if the precautions for use are followed. Vaccination is less efficient, as in immunocompromised patients, and needs specific protocols.

Hepatic encephalopathy is a severe complication of liver cirrhosis and is an important therapeutic challenge, with a social and economic issue. If, now, the pathophysiology is not totally understood (main role of ammonia, but a better understanding of cerebral mechanisms), the clinical presentation is well-known. Some treatments are useful (disaccharides, treatment of the trigger) but their efficiency is limited. Nevertheless, the emergence of new treatments, such as non-absorbable antibiotics (rifaximin essentially), is an interesting therapeutic tool.

We report the case of a 17-year-old male admitted to our academic hospital with massive rectal bleeding. Since childhood he had reported recurrent gastrointestinal bleeding and had two exploratory laparotomies 5 and 2 years previously. An emergency abdominal computed tomography scan, gastroscopy and colonoscopy, performed after hemodynamic stabilization, were considered normal. High-dose intravenous proton pump inhibitor (PPI) therapy was initiated and bleeding stopped spontaneously. Two other massive rectal bleeds occurred 8 h after each cessation of PPI which led to a hemostatic laparotomy after negative gastroscopy and small bowel capsule endoscopy. This showed long tubular duplication of the right colon, with fresh blood in the duplicated colon. Obscure lower gastrointestinal bleeding is a difficult medical situation and potentially life-threatening. The presence of ulcerated ectopic gastric mucosa in the colonic duplication explains the partial efficacy of PPI therapy. Obscure gastrointestinal bleeding responding to empiric anti-acid therapy should probably evoke the diagnosis of bleeding ectopic gastric mucosa such as Meckel’s diverticulum or gastrointestinal duplication, and gastroenterologists should be aware of this potential medical situation.

Hepatitis C virus (HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease (CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in end-stage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents (DAAs) while avoiding peginterferon and ribavirin. The first results were convincing. To aid in the correct use of these drugs in patients with renal insufficiency, their pharmacokinetic properties and potential renal toxicity must be known. The renal toxicity of these new drugs was not a safety signal in clinical trials, and the drugs are generally efficient in these frail populations. These drugs are usually well tolerated, but recent cohort studies have demonstrated that these new regimens may be associated with renal side effects, especially when using sofosbuvir combinations. HCV, renal diseases and comorbidities are intimately linked. The close monitoring of renal function is required, particularly for at-risk patients (transplanted, HIV-coinfected, CKD, hypertensive or diabetic patients). New DAA regimens, which will soon be approved, will probably change the landscape.

Introduction Les atteintes digestives touchent plus de la moitie des malades souffrant de syndrome de Gougerot-Sjogren (SGS). Les symptomes digestifs hauts (epigastralgies, nausees, vomissements, inconfort epigastrique…) sont tres frequents [1] . Une seule etude a rapporte un retard de vidange gastrique chez 28 patients souffrant de SGS primitifs compares a 50 volontaires sains sans lien avec une quelconque symptomatologie [2] . Nous rapportons une cohorte retrospective de patients souffrant de SGS avec une gastroparesie identifiee par scintigraphie de vidange gastrique dans le cadre de symptomes digestifs hauts inexpliques. Patients et methodes Cohorte retrospective descriptive de patients souffrant de SGS primitifs averes selon la classification americano-europeenne avec une gastroparesie definie par des symptomes digestifs hauts inexpliques associees a un ralentissement significatif de la vidange gastrique (T1/2 > 113 min) lors d’une scintigraphie. Les symptomes digestifs hauts etaient consideres « inexpliques » en absence d’atteinte organique (FOGD normale, pas d’Helicobacter pylori) et ne repondant pas aux IPP. Resultats Entre septembre 2013 et juillet 2015, 7 patients SGS ont ete consideres gastroparetiques. Le temps moyen de demi-vidange gastrique etait de 521 min. Le delai moyen entre les symptomes digestifs hauts et le diagnostic de gastroparesie etait long (> 24 mois) ; 57,1 % decrivaient des douleurs epigastriques, 71,4 % une sensation de pesanteur post-prandiale, 42,8 % des nausees et 28,5 % un amaigrissement avec des signes de denutrition en lien avec leur trouble digestif. Tous souffraient d’un syndrome sec buccal ou oculaire, 100 % avaient des ANA positifs (50 % = SSA/B) et 75 % une atteinte articulaire inflammatoire ; 71,4 % souffraient d’une atteinte neurologique (centrale 14,2 %, axonale 14,2 %, des petites fibres 14,2 % ou vegetative 28,5 %). Parmi les patients, 71,4 % ont ete traites par Plaquenil et 57,1 % par Immunosuppresseurs dans le cadre d’une atteinte articulaire ou cutanee evolutive. Conclusion La gastroparesie doit etre evoquee chez les patients souffrant de SGS et presentant des symptomes digestifs hauts inexpliques. La scintigraphie de vidange gastrique represente le gold standard pour poser ce diagnostic. Une atteinte neurologique du SGS pourrait expliquer ce trouble. Une cohorte prospective evaluant systematiquement le temps de vidange gastrique en cas de symptomes digestifs hauts inexpliques est necessaire pour evaluer la prevalence precise de la gastroparesie dans cette population et identifier des facteurs de risque.

Summary Sirolimus is currently used as an immunosuppressive agent in kidney transplantation due to its lack of nephrotoxicity and antiproliferative properties. However, a large number of side effects has been described with the use of mTor inhibitors. Most are reversible when treatment is withdrawn. Hepatotoxicity is one of these side effects, considered as a benign condition and resulting generally in a transitory and small increase in transaminase levels. We report here, to the best of our knowledge, the first case of severe sirolimus-induced acute hepatitis confirmed by liver biopsy, in a renal transplant recipient. This condition was completely cured in few weeks after sirolimus withdrawal.

A Novel Hemostatic Powder for the Endoscopic Treatment of Gastrointestinal Bleeding: Results From a Multicenter Prospective Study Performed in Routine Practice (the ‘Graphe' Registry) Sami Haddara, Julien Branche, Stephane Lecleire, Jeremie Jacques, Laurent Heyries, Jocelyn Privat, Philippe Bichard, Philippe Grandval, Yann Lebaleur, Ulriikka Chaput, Stephane Koch, Jonathan Levy, Bruno Godart, Antoine Charachon, Jean-Francois Bourgaux, Emmanuel Coron