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Patients with one-anastomosis gastric bypass (OAGB) can develop gastroesophageal reflux disease (GERD). The nature of this GERD (acid or biliary) remains unclear. To assess the nature of GERD via impedance pH testing in patients presenting with reflux post OAGB. Retrospective analysis of a prospectively collected database of 43 patients with OAGB backgrounds who developed postoperative GERD and were investigated with impedance pH monitoring between 2006 and 2019. Mean age was 52.48 ± 9 years. Mean body mass index (BMI) prior to OAGB was 46.82 kg/m2. None of these patients had clinical GERD before surgery. The median time interval between surgery and investigation with 24-h impedance pH monitoring was 64 (56) months. The mean BMI at the time of investigations was 32.67 ± 6.9 kg/m2. The type of reflux was acid in 13 (30.2%), non-acid (biliary) in 12 (27.9%), and mixed (acid and biliary) in 5 (11.6%) patients. However, it remained not confirmed in 13 (30.2%). Median DeMeester score was 48.95 (27.67) in patients with acid, 2.8 (7.4) in patients with biliary, and 28.7 (5.6) in patients with mixed reflux. Median percent of time spent with pH < 4 was 9.65 (8) in patients with acid, 0.6 (1.75) in patients with biliary, and 7.7 (3.9) in patients with mixed reflux. Acid reflux seems to be as common as bile reflux in patients presenting with GERD after OAGB. In case of revisional surgery for severe GERD post OAGB, 24-h impedance pH monitoring could be essential to determine the surgical procedure of choice.

International audience; In this study, we investigated the combination of extracellular (nano) vesicles (EVs) from pig adipose tissue-derived stromal cells (ADSCs) and a thermoresponsive gel, Pluronic (R) F-127 (PF-127), to prevent stricture formation after endoscopic resection in a porcine model. ADSC EVs were produced at a liter scale by a high-yielding turbulence approach from ADSCs 3D cultured in bioreactors and characterized in terms of size, morphology and membrane markers. The thermoresponsive property of the PF-127 gel was assessed by rheology. The pro-regenerative potency of ADSC EVs was investigated ex vivo in esophageal biopsies under starvation. In vivo tests were performed in a porcine model after extended esophageal endoscopic mucosal dissection (ESD). Pigs were randomized into 3 groups: control (n = 6), gel (n = 6) or a combination of 1.45 x 10(12) EVs + gel (n = 6). Application of gel +/- EVs was performed just after ESD with a follow-up finalized on day 21 post-ESD. There was a trend towards less feeding disorder in the EV + gel group in comparison with the gel and the control groups (16.67% vs. 66.7% vs. 83.33%, respectively) but without reaching a statistically significant difference. A significant decrease in the esophageal stricture rate was confirmed by endoscopic, radiological and histological examination for the EV + gel group. A decrease in the mean fibrosis area and larger regenerated muscularis mucosae were observed for the EV + gel group. In summary, the application of EVs + gel after extended esophageal endoscopic resection succeeded in preventing stricture formation with an anti-fibrotic effect. This nano-therapy may be of interest to tackle an unmet medical need considering that esophageal stricture is the most challenging delayed complication after extended superficial cancer resection by endoscopy.

Extracellular vesicles (EVs), especially from stem/stromal cells (SCs), represent a cell-free alternative in regenerative medicine holding promises to promote tissue healing while providing safety and logistic advantages in comparison to cellular counterparts. Herein, we hypothesize that SC EVs, administered locally in a thermoresponsive gel, is a therapeutic strategy for managing post-surgical colo-cutaneous fistulas. This disease is a neglected and challenging condition associated to low remission rates and high refractoriness. Herein, EVs from a murine SC line were produced by a high-yield scalable method in bioreactors. The post-surgical intestinal fistula model was induced via a surgical cecostomy communicating the cecum and the skin in Wistar rats. Animals were treated just after cecostomy with PBS, thermoresponsive Pluronic F-127 hydrogel alone or containing SC EVs. A PET-monitored biodistribution investigation of SC EVs labelled with 89Zr was performed. Fistula external orifice and output assessment, probe-based confocal laser endomicroscopy, MRI and histology were carried out for therapy follow-up. The relevance of percutaneous EV administration embedded in the hydrogel vehicle was indicated by the PET-biodistribution study. Local administration of SC EVs in the hydrogel reduced colo-cutaneous fistula diameter, output, fibrosis and inflammation while increasing the density of neo-vessels when compared to the PBS and gel groups. This multi-modal investigation pointed-out the therapeutic potential of SC EVs administered locally and in a thermoresponsive hydrogel for the management of challenging post-surgical colon fistulas in a minimally-invasive cell-free strategy.

Background and Aims Histological healing may represent the ultimate therapeutic goal in ulcerative colitis [UC], but it requires biopsies. Our aim was to develop a non-invasive index able to assess histological disease activity in ulcerative colitis, using probe-based confocal laser endomicroscopy [pCLE]. Methods One hundred patients with quiescent UC were prospectively included in five French centres. After fluorescein intravenous injection, during colonoscopy, the colorectal mucosa was analysed by white light imaging and pCLE, and then biopsied in different locations. Five endoscopists performed central reading of pCLE images blinded to clinical, endoscopic, and histological data. One expert pathologist performed a central histological reading [Nancy index: gold standard]. Univariate and multivariate analyses were performed to identify the endomicroscopic items associated with the presence of histologically active disease. Results Over 1000 pCLE videos sequences performed in 100 UC patients in endoscopic remission [Mayo 0 and 1] were evaluated. We observed that vessel diameter >20 µm, dilated crypt lumen, fluorescein leakage, and irregular crypt architecture were statistically associated with histologically proven inflammation according to the Nancy index. Hence, we built a pCLE index of mucosal inflammation with overall accuracy of 79.6% and overall sensitivity and specificity of, respectively, 57.8% and 82.8%. Negative predictive value, especially when a pCLE index ≤1 was observed, was high [93.1%]. Conclusions Using a robust methodology, large vessel diameter, dilated crypt lumen, fluorescein leakage,and irregular crypt architecture are reliable endomicroscopic items defining the ENHANCE index for real-time assessment of histological disease activity in UC.

Background Narrow-band imaging (NBI) is as sensitive as Lugol chromoendoscopy to detect esophageal squamous cell carcinoma (SCC) but its specificity, which appears higher than that of Lugol chromoendoscopy in expert centers, remains to be established in general practice. This study aimed to prove the superiority of NBI specificity over Lugol chromoendoscopy in the detection of esophageal SCC and high grade dysplasia (HGD) in current general practice (including tertiary care centers, local hospitals, and private clinics). Methods This prospective randomized multicenter trial included consecutive patients with previous or current SCC of the upper aerodigestive tract who were scheduled for gastroscopy. Patients were randomly allocated to either the Lugol or NBI group. In the Lugol group, examination with white light and Lugol chromoendoscopy were successively performed. In the NBI group, NBI examination was performed after white-light endoscopy. We compared the diagnostic characteristics of NBI and Lugol chromoendoscopy in a per-patient analysis. Results 334 patients with history of SCC were included and analyzed (intention-to-treat) from 15 French institutions between March 2011 and December 2015. In per-patient analysis, sensitivity, specificity, positive and negative likelihood values were 100 %, 66.0 %, 21.2 %, and 100 %, respectively, for Lugol chromoendoscopy vs. 100 %, 79.9 %, 37.5 %, and 100 %, respectively, for NBI. Specificity was greater with NBI than with Lugol (P = 0.002). Conclusions As previously demonstrated in expert centers, NBI was more specific than Lugol in current gastroenterology practice for the detection of early SCC, but combined approaches with both NBI and Lugol could improve the detection of squamous neoplasia.

Lynch syndrome (LS) is an inherited predisposition to colorectal cancer (CRC), responsible for 3-5% of all CRC. This syndrome is characterized by the early occurrence of colorectal neoplastic lesions, with variable incidences depending on the type of pathogenic variants in MMR genes (MLH1, MSH2, MSH6, PMS2 and EPCAM) and demographics factors such as gender, body mass index, tobacco use and physical activity. Similar to sporadic cancers, colorectal screening by colonoscopy is efficient because it is associated with a reduction >50% of both CRC incidence and CRC related mortality. To that end, most guidelines recommend high definition screening colonoscopies in dedicated centers, starting at the age of 20-25 years old, with a surveillance interval of 1-2 years. In this review, we discuss the importance of high definition colonoscopies, including the compliance to specific key performance indicators, as well as the expected benefits of specific imaging modalities including virtual chromoendoscopy and dye-spray chromoendoscopy.

Resume Les patients presentant une predisposition genetique aux cancers digestifs sont a haut risque de developper une neoplasie et doivent etre suivis au sein de reseaux specialises. Le reseau PRED-IdF a ete mis en place par l’INCa en 2009 pour l’ensemble de la region Ile-de-France et comporte depuis 2012 (deploiement du dispositif national d’oncogenetique) 7 centres experts dans la prise en charge des predispositions genetiques aux cancers digestifs. L’objectif de ce reseau est de proposer aux patients une prise en charge et un suivi multidisciplinaire specifique a chaque syndrome de predisposition. Tout patient presentant une suspicion de syndrome de predisposition peut etre adresse a l’un des centres du reseau pour un avis specialise. Les principales missions du reseau incluent l’etablissement d’un plan personnalise de suivi (PPS) et sa coordination, la mise en place d’activite de recours et d’expertise pour les cas difficiles et le developpement de l’activite recherche. Depuis 2009, 3384 patients ont ete inclus dans le reseau dont 1925 pour syndrome de Lynch et 539 pour polypose adenomateuse familiale (mutations APC et MUTYH), representant ainsi 72,8 % de la cohorte PRED-IdF. L’impact benefique du reseau a ete recemment demontre pour les patients suivis pour syndrome de Lynch, marque par une diminution de la survenue de cancers colorectaux apres inclusion. Le reseau s’implique aussi dans de nombreux projets de recherche, allant du developpement de collaborations en recherche fondamentale a la participation aux etudes controlees randomisees. L’objectif a terme, etant de proposer une medecine personnalisee a l’ensemble des patients inclus dans le reseau.

INTRODUCTION: Enteroscopy resection of small bowel polyps in Peutz-Jeghers syndrome has only been described in small case series. Herein, we aimed to assess the efficacy of enteroscopy resection of small bowel polyps within a specialised tertiary care centre and the impact on intraoperative enteroscopy. METHODS: This was an observational single-centre study. All adult Peutz-Jeghers syndrome patients followed in the Predisposition Digestive Ile-de-France network who underwent an endoscopic resection of at least one small bowel polyp ≥ 1 cm by enteroscopy between 2002–2015 were included. Small bowel polyps were detected under a dedicated screening programme by previous capsule endoscopy and/or magnetic resonance enterography, performed every 2–3 years. Complete treatment was defined as the absence of polyps ≥ 1 cm after conventional endoscopic resection. Intraoperative enteroscopy or surgical resection were indicated in incomplete treatments. The overall complete treatment rate including conventional enteroscopy and intraoperative enteroscopy was also considered. RESULTS: Endoscopic resection of 216 small bowel polyps (median: 8.6 per patient, size: 6–60 mm) was performed by 50 enteroscopies in 25 patients (mean age: 36 years, range: 18–71, 56% male) with small bowel polyp ≥ 1 cm. Twenty-three patients (92%) underwent 42 screening capsule endoscopies and 14 (57%) had 23 magnetic resonance enterographies during a median follow-up of 60 months. Complete treatment was achieved in 76%. Intraoperative enteroscopy and surgical resection were performed in four (16%) and two (8%) patients. Intraoperative enteroscopy improved by 16% the complete treatment rate and the overall rate was 92%. The complication rate was 6%. CONCLUSION: This long-term study confirmed the efficacy and safety of endoscopic resection of small bowel polyps in Peutz-Jeghers syndrome. Intraoperative enteroscopy can be a complementary approach in selected cases.

Summary Background Refractory coeliac disease type 2 is a rare subtype of coeliac disease with high mortality rates; interleukin 15 (IL-15) is strongly implicated in its pathophysiology. This trial aimed to investigate the effects of AMG 714, an anti-IL-15 monoclonal antibody, on the activity and symptoms of refractory coeliac disease type 2. Methods This was a randomised, double-blind, placebo-controlled, phase 2a study of adults with a confirmed diagnosis of refractory coeliac disease type 2. Patients were randomly assigned at a 2:1 ratio to receive seven intravenous doses over 10 weeks of AMG 714 (8 mg/kg) or matching placebo. Biopsy samples were obtained at baseline and week 12 for cellular analysis and histology. The change in the proportion of aberrant intraepithelial lymphocytes from baseline to week 12 with respect to all intraepithelial lymphocytes was the primary endpoint and was quantified using flow cytometry. Secondary endpoints were the change in aberrant intraepithelial lymphocytes with respect to intestinal epithelial cells; intestinal histological scores (villous height-to-crypt depth ratio; VHCD); intraepithelial lymphocyte counts; Marsh score; and patient-reported symptom measures, including the Bristol stool form scale (BSFS) and gastrointestinal symptom rating scale (GSRS). Main analyses were done in the per-protocol population of patients who received their assigned treatment, provided evaluable biopsy samples, and did not have major protocol deviations; only patients with non-atypical disease were included in the analyses of aberrant intraepithelial lymphocytes, including the primary analysis. Safety was assessed in all patients who received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02633020) and EudraCT (2015-004063-36). Findings From April 13, 2016, to Jan 19, 2017, 28 patients were enrolled and randomly assigned to AMG 714 (n=19) and placebo (n=9). Six patients were not included in the primary analysis because of protocol deviation (one in the AMG 714 group), insufficient biopsy samples (one in the AMG 714 group), and atypical intraepithelial lymphocytes (three in the AMG 714 group and one in the placebo group). At 12 weeks, the least square mean difference between AMG 714 and placebo in the relative change from baseline in aberrant intraepithelial lymphocyte percentage was −4·85% (90% CI −30·26 to 20·56; p=0·75). The difference between the AMG 714 and placebo groups in aberrant intraepithelial lymphocytes with respect to epithelial cells at 12 weeks was −38·22% (90% CI −95·73 to 19·29; nominal p=0·18); the difference in change in Marsh score from baseline was 0·09% (95% CI −1·60–1·90; nominal p=0·92); the difference in VHCD ratio was 10·67% (95% CI −38·97 to 60·31; nominal p=0·66); and the difference in change in total intraepithelial lymphocyte count was −12·73% (95% CI −77·57–52·12); nominal p=0·69). Regarding symptoms, the proportion of patients with diarrhoea per the BSFS score decreased from ten (53%) of 19 at baseline to seven (37%) of 19 at week 12 in the AMG 714 group and increased from two (22%) of nine at baseline to four (44%) of nine at week 12 in the placebo group (nominal p=0·0008); and the difference between the groups in change in GSRS score was −0·14 (SE 0·19; nominal p=0·48). Eight (89%) patients in the placebo group and 17 (89%) in the AMG 714 group had treatment-emergent adverse events, including one (11%) patient in the placebo group and five (26%) in the AMG 714 group who had serious adverse events. The most common adverse event in the AMG 714 group was nasopharyngitis (eight [42%] patients vs one [11%] in the placebo group). Interpretation In patients with refractory coeliac disease type 2 who were treated with AMG 714 or placebo for 10 weeks, there was no difference between the groups in terms of the primary endpoint of aberrant intraepithelial lymphocyte reduction from baseline. Effects on symptoms and other endpoints suggest that further research of AMG 714 may be warranted in patients with refractory coeliac disease type 2. Funding Celimmune and Amgen.

Endoscopic submucosal dissection (ESD) is a validated treatment for early rectal tumors, but whether this therapy is efficient or not for rectal tumors extending to the dentate line (RTDL) remains unclear. We performed a systematic review and meta-analysis to assess the effectiveness and safety of ESD in RTDL compared to non-RTDL. A search in PubMed, Scopus and the Cochrane library up to April 2020 was conducted to identify studies that compared ESD in both localizations (RTDL and non-RTDL), reporting at least one main outcome (en bloc, complete resection, recurrence). Secondary outcomes were adverse event occurrence. Five observational studies including 739 patients with a total of 201 RTDL and 538 non-RTDL were considered. The proportion of female sex (66% vs. 36.9%, P0.001) and tumor size [mean difference = 7.75, 95% confidence interval (CI): 3.01-12.49, P = 0.001] were higher in the RTDL group. There were no differences in en bloc resection rates between RTDL and non-RTDL groups [odds ratio (OR): 0.95, 95% CI: 0.50-1.79, P = 0.087]. The complete resection rate was significantly higher in the non-RTDL group (OR: 1.72, 95% CI: 1.18-2.53, P = 0.005, I2 = 0%). However, recurrence rates were comparable (RD: -0.04, 95% CI: -0.07 to 0.00, P = 0.06, I2 = 0%). Concerning adverse events, there were no differences in terms of perforation (OR: 0.9, 95% CI: 0.26-3.08, P = 0.86, I2 = 0%) or delayed bleeding (OR: 0.64, 95% CI: 0.17-2.42, P = 0.51, I2 = 35%). Anal pain rate was 28% (95% CI: 21.4-35.8%). ESD is an effective and safe therapeutic approach for RTDL with comparable recurrence rate to non-RTDL. The lower complete resection rate in RTDL needs to be clarified in studies.

This guideline presents recommendations for the management of coeliac disease (CD) and other gluten-related disorders both in adults and children. There has been a substantial increase in the prevalence of CD over the last 50 years and many patients remain undiagnosed. Diagnostic testing, including serology and biopsy, should be performed on a gluten-containing diet. The diagnosis of CD is based on a combination of clinical, serological and histopathological data. In a group of children the diagnosis may be made without biopsy if strict criteria are available. The treatment for CD is primarily a gluten-free diet (GFD), which requires significant patient education, motivation and follow-up. Slow-responsiveness occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms necessitate a review of the original diagnosis, exclude alternative diagnoses, confirm dietary adherence (dietary review and serology) and follow-up biopsy. In addition, evaluation to exclude complications of CD, such as refractory CD or lymphoma, should be performed. The guideline also deals with other gluten-related disorders, such as dermatitis herpetiformis, which is a cutaneous manifestation of CD characterized by granular IgA deposits in the dermal papillae. The skin lesions clear with gluten withdrawal. Also, less well-defined conditions such as non-coeliac gluten sensitivity (NCGS) and gluten-sensitive neurological manifestations, such as ataxia, have been addressed. Newer therapeutic modalities for CD are being studied in clinical trials but are not yet approved for use in practice.

Background: Patients with Lynch syndrome are at increased risk of gastric and duodenal cancer. Upper gastrointestinal endoscopy surveillance is generally proposed, even though little data are available on upper gastrointestinal endoscopy in these patients. The aim of this retrospective study was to evaluate the prevalence and incidence of gastrointestinal lesions following upper gastrointestinal endoscopy examination in Lynch patients. Methods: A large, multicentre cohort of 172 patients with a proven germline mutation in one of the mismatch repair genes and at least one documented upper gastrointestinal endoscopy screening was assessed. Detailed information was collected on upper gastrointestinal endoscopy findings and the outcome of endoscopic follow-up. Results: Seventy neoplastic gastrointestinal lesions were diagnosed in 45 patients (26%) out of the 172 patients included. The median age at diagnosis of upper gastrointestinal lesions was 54 years. The prevalence of cancer at initial upper gastrointestinal endoscopy was 5% and the prevalence of precancerous lesions was 12%. Upper gastrointestinal lesions were more frequent after 40 years of age (p &lt, 0.001). Helicobacter pylori infection was associated with an increased prevalence of gastric, but not duodenal, lesions (p &lt, 0.001). Conclusions: Neoplastic upper gastrointestinal lesions are frequent in patients with Lynch syndrome, especially in those over 40 years of age. The results of our study suggest that Lynch patients should be considered for upper gastrointestinal endoscopic and Helicobacter pylori screening.

ObjectiveEnteropathy-associated T-cell lymphoma (EATL) is a rare but severe complication of celiac disease (CeD), often preceded by low-grade clonal intraepithelial lymphoproliferation, referred to as type II refractory CeD (RCDII). Knowledge on underlying oncogenic mechanisms remains scarce. Here, we analysed and compared the mutational landscape of RCDII and EATL in order to identify genetic drivers of CeD-associated lymphomagenesis.DesignPure populations of RCDII-cells derived from intestinal biopsies (n=9) or sorted from blood (n=2) were analysed by whole exome sequencing, comparative genomic hybridization and RNA-sequencing. Biopsies from RCDII (n=50), EATL (n=19), type I refractory CeD (n=7) and uncomplicated CeD (n=7) were analysed by targeted next-generation sequencing. Moreover, functional in vitro studies and drug testing were performed in RCDII-derived cell lines.Results80% of RCDII and 90% of EATL displayed somatic gain-of-functions mutations in the JAK1-STAT3 pathway, including a remarkable p.G1097 hotspot mutation in the JAK1 kinase-domain in approximately 50% of cases. Other recurrent somatic events were deleterious mutations in NFκB-regulators TNFAIP3 and TNIP3 and potentially oncogenic mutations in TET2, KMT2D and DDX3X. JAK1 inhibitors and the proteasome inhibitor bortezomib could block survival and proliferation of malignant RCDII-cell lines.ConclusionMutations activating the JAK1-STAT3 pathway appear to be the main drivers of CeD-associated lymphomagenesis. In concert with mutations in negative regulators of NFκB, they may favour the clonal emergence of malignant lymphocytes in the cytokine-rich coeliac intestine. The identified mutations are attractive therapeutic targets to treat RCDII and block progression towards EATL.

Summary This case report relates to the first-in-man use of a vessel occluder gel medical device as a fistula occluder in a repurposing strategy. A patient with chronic colocutaneous fistula received an off-label treatment with a thermoresponsive Poloxamer 407 gel (20%) via percutaneous administration and injected under endoscopic control. Treatment consisted in the association of esophageal stent placement and gel injection. The product was administered just after the stent placement at

Background and aims: The role of small bowel neoplasia (SBN) screening in asymptomatic patients with Lynch syndrome (LS) is uncertain. The aim of our study was to assess the effectiveness of screening by capsule endoscopy (CE) in these patients. Methods: This study was an observational, analytical, and retrospective single-center study within the PRED-IdF network. All consecutive asymptomatic patients older than 35 years-old with confirmed LS and no personal history of SBN who started the screening from 2010–2015 were included. The baseline screening and 24 months follow-up were performed by CE. The CE diagnostic yield (positive tumor or polyp) and accuracy, using the follow-up as gold standard, were evaluated. Results: A total of 150 patients underwent the SBN screening program and 135 (52.7 ± 11.2 years-old, 37.8% male) met the inclusion criteria. The baseline CE diagnostic yield was 4.4% (3 polyps, 3 tumors) and the proximal small bowel was the most common location ( n = 4, 66.7%). In total, 87 patients underwent follow-up and the diagnostic yield was 4.6%. Four patients were considered positive at follow-up (2 adenomas, 2 adenocarcinomas). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CE were 60%, 100%, 100%, 96.9%, and 97%, respectively. Conclusions: CE is an accurate procedure for baseline screening of SBN in LS patients and may be efficient for follow-up procedures. However, the optimal starting age of screening and intervals of follow-up must be clarified.

Introduction: the aim of this study was to determine the risk factors for rebleeding following device-assisted enteroscopy therapy of small bowel vascular lesions. Methods: this is a systematic review and meta-analysis. A literature search was performed from January 2003 to October 2019. All studies reporting on at least one risk factor for bleeding recurrence after endoscopic therapy of small bowel vascular lesions were included. A meta-analysis of those risk factors reported in at least three studies was performed to assess their association with rebleeding. The OR and 95 % CI were used for binary outcome data. Heterogeneity analysis was performed using the Tau and I2 index. If I2 > 20 %, potential sources of heterogeneity were identified by sensitivity analyses and a random-effect model was used. Results: the search identified a total of 572 articles and 35 full-text records were assessed for eligibility after screening. Finally, eight studies that included 548 patients were selected. The overall median rebleeding rate was 38.5 % (range: 10.9-53.3 %) with a median follow-up of 24.5 months. Female sex (OR: 1.96, 95 % CI: 1.14-3.37, p = 0.01, I2 = 0 %), Osler-Weber syndrome (OR: 4.35, 95 % CI: 1.22-15.45, p = 0.02, I2 = 0 %) and cardiac disease (OR: 1.89, 95 % CI: 1.12-2.97, p = 0.005, I2: 0 %) were associated with rebleeding. According to the sensitivity analysis, overt bleeding (OR: 2.13, 95 % CI: 1.22-3.70, p = 0.007, I2 = 0 %), multiple lesions (OR: 4.57, 95 % CI: 2.04-10.22, p < 0.001, I2 = 0 %) and liver cirrhosis (OR: 2.61, 95 % CI: 1.11-6.13, p = 0.03, I2 = 0 %) were also predictors for rebleeding. Conclusions: patient characteristics and comorbidities should be considered for follow-up patient management after effective device-assisted endoscopic therapy, as they can predict rebleeding.

BackgroundHemodynamic monitoring during digestive endoscopy is usually minimal and involves intermittent brachial pressure measurements. New continuous noninvasive devices to acquire instantaneous arterial blood pressure may be more sensitive to detect procedural hypotension.PurposeTo compare the ability of noninvasive continuous monitoring with that of intermittent oscillometric measurements to detect hypotension during digestive endoscopy.MethodsIn this observational prospective study, patients scheduled for gastrointestinal endoscopy and colonoscopy under sedation were monitored using intermittent pressure measurements and a noninvasive continuous technique (ClearSight™, Edwards). Stroke volume was estimated from the arterial pressure waveform. Mean arterial pressure and stroke volume values were recorded at T1 (prior to anesthetic induction), T2 (after anesthetic induction), T3 (gastric insufflation), T4 (end of gastroscopy), T5 (colonic insufflation). Hypotension was defined as mean arterial pressure < 65 mmHg.ResultsTwenty patients (53±17 years) were included. Six patients (30%) had a hypotension detected using intermittent pressure measurements versus twelve patients (60%) using noninvasive continuous monitoring (p = 0.06). Mean arterial pressure decreased during the procedure with respect to T1 (p < 0.05), but the continuous method provided an earlier warning than the intermittent method (T3 vs T4). Nine patients (45%) had at least a 25% reduction in stroke volume, with respect to baseline.ConclusionNoninvasive continuous monitoring was more sensitive than intermittent measurements to detect hypotension. Estimation of stroke volume revealed profound reductions in systemic flow. Noninvasive continuous monitoring in high-risk patients undergoing digestive endoscopy under sedation could help in detecting hypoperfusion earlier than the usual intermittent blood pressure measurements.

Post-laparoscopic sleeve gastrectomy (LSG) fistula is a major complication, responsible for high morbidity. Endoscopic treatment represents an alternative to surgical management, with variable approaches and success rates. In this study, we aimed to evaluate the efficacy of endoscopic treatment in a tertiary care center. Between March 2010 and March 2015, all patients referred to our center for endoscopic treatment of fistula related to laparoscopic sleeve gastrectomy were included. The primary endpoint was defined as a complete closure of the fistula without recurrence within the 2 months. A total of 26 patients were retrospectively included (73% female). The mean time between fistula diagnosis and first endoscopy was 27.4 days (± 22). Twenty-three (88.4%) patients had a complete fistula closure after endoscopic treatment. The healing delay was 76.4 days (± 42.8), and an average of 3.5 (± 1.4) endoscopic procedures were required. Clinical efficacy was 100% when the endoscopic treatment was performed within the first 3 weeks, or 70% afterwards (p = 0.046). The fistula closure rate was similar between patients with endoscopic drainage (with or without other endoscopic techniques) and patient with closing techniques alone (85.7% vs. 89.5%, respectively). Endoscopic treatment of fistula after LSG is efficient but requires early procedures within the first 3 weeks. Endoscopic strategies involving closing procedure or drainage procedure seem to be similar, but these data must be confirmed in large prospective clinical studies.

Extreme hypomagnesemia (hypoMg) can be encountered in many situations, but little data currently exist. Our aim is to describe the epidemiological, clinical, etiological characteristics, and the biological abnormalities of consecutive inpatients with extreme hypomagnesemia. In our observational monocentric study, between 1st July 2000 and April 2015, all inpatients with extreme hypomagnesemia, defined by at least one plasma magnesium concentration (PMg) below 0.3 mmol/L, were included. Demographic, clinical, biological characteristics and the drugs prescribed before the qualifying PMg measurement were retrospectively collected. 41,069 patients had at least one PMg assessment. The prevalence of extreme hypomagnesemia is 0.3% (119 inpatients). The median age is 70 years, 52% are women. The patients were mainly hospitalized in intensive care (n = 37, 31.1%), oncology (n = 21, 17.6%), gastroenterology (n = 18, 15.1%) and internal medicine (n = 16, 13.4%) departments. One hundred patients (84%) had a medical history of gastrointestinal disease (39% with bowel resections, 24% with stoma), and 50 (42%) had a cancer history. The drugs most commonly prescribed (known to induce hypoMg) are proton pump inhibitors (PPI) (n = 77, 70%), immunosuppressive regimens (n = 25, 22.5%), platinum salt-based chemotherapies (n = 19, 17.1%), and diuretics (n = 22, 19.8%). The suspected causes of hypomagnesemia are often multiple, but drugs (46%, including PPI in 19%) and chronic gastrointestinal disorders (37%) are prominent. Associated electrolyte disturbances include hypocalcemia (77%) and mild hypokalemia (51%). The 1-month mortality from all causes is 16%. Extreme hypomagnesemia is rare in inpatients, and is frequently associated with severe hypocalcemia. Digestive disorders and drugs are the main contributory causes.

Background and study aims Large scale data on esophagogastroduodenoscopy (EGD) in Western countries are scarce. We conducted a prospective study on the diagnostic yield of upper gastrointestinal endoscopy in France. Patients and methods An online questionnaire was sent to all French gastroenterologists practicing endoscopy. Data from EGDs performed during one week were collected. A statistical extrapolation of the results to a whole year was performed. Results 342 gastrointestinal endoscopists, representative of the population of French gastroenterologists, provided data on 2735 EGDs, corresponding to 1 006 316 (95%CI = 937 080−1 075 552) procedures for the entire year. 1770 (64.7%) EGDs were performed under sedation or general anesthesia, and 930 (34%) were associated with a colonoscopy. 896 (32.8%) EGDs were normal. Hiatal hernia and esophagitis were the most frequent esophageal diagnoses, in 496 (18.1%) and 374 (13.7%) cases, respectively. Barrett’s esophagus was diagnosed in 109 (4%) patients. Among gastric lesions, endoscopic gastritis was reported in 572 (20.9%) patients; ulcer, polyps, and suspected malignancy in 78 (2.9%), 62 (2.3%), and 19 (0.7%), respectively. 1597 (58.4%) EGDs included mucosal biopsies, and 141 (5.1%) were associated with a therapeutic procedure. Conclusions We report nationwide prospective data on upper gastrointestinal endoscopy practice in France. Our data suggest that about 300 000 normal EGDs each year in France could potentially be avoided by a diagnostic strategy relying on upper GI capsule endoscopy, providing significant relief on healthcare practitioners.

Background and study aims Over-the-scope clip (OTSC) has been recently used in management of gastrointestinal perforations, but data on it are still limited. The aim of this study was to compare management of iatrogenic perforations before and after the OTSC was available in our endoscopy unit. Patients and methods We conducted a monocentric retrospective study from June 2007 to June 2015. All iatrogenic gastrointestinal perforations detected during endoscopy were included. Two time periods were compared in terms of surgery and mortality rates: before use of OTSC (June 2007 to June 2011) and after OTSC became available (June 2011 to June 2015). Results During the first period, 24 perforations were recorded. Fifteen (62.5 %) were managed with surgery. The mortality rate was 8 %. During the second period, 16 perforations occurred. In 11 patients (68.7 %), an OTSC was used to close the perforation, with complete sealing of the perforation in 100 % of cases. However, 2 patients with sigmoid perforation had to undergo surgery due to right ureteral obstruction by the clip in 1 case and to presence of a localized peritonitis in the other. The surgery rate during this period was 12.5 % (2 /16), with a statistically significant difference compared to the first period (P = 0.002). There was no mortality in the second period versus 8 % in the first one (P = 0.23). Conclusions OTSC is effective for endoluminal closure of iatrogenic perforations and results in a significant decrease in surgery rate.

Intraoperative enteroscopy (IOE) to explore obscure gastrointestinal bleeding is now rarely indicated. IOE allows complete small bowel exploration in 57% to 100% of cases, finds a bleeding source in 80% of cases, allows the recurrence-free management of gastrointestinal bleeding in 76% of cases, but carries a high morbidity and mortality. IOE only remains indicated to guide the intraoperative treatment of preoperatively identified small bowel lesions when nonoperative treatments are unavailable and/or when intraoperative localization by external examination is impossible.

Colonoscopic screening with indigo carmine chromoendoscopy (ICC) in patients with Lynch syndrome (LS) improves the adenoma detection rate but is time consuming and poorly used in clinical practice. Narrow-band imaging (NBI), a virtual chromoendoscopy technique, highlights superficial mucosal vessels and improves adenoma characterization. We conducted a prospective multicenter trial in a back-to-back fashion to compare the third-generation NBI with ICC for detecting colonic adenomas in patients with LS.In a multicenter, prospective, noninferiority trial, 138 patients underwent a double colonoscopy, first with NBI, followed by ICC, in a back-to-back design. The primary noninferiority outcome measure was the number of patients with at least one adenoma after NBI compared with the number of patients with at least one adenoma after NBI and ICC.The 138 analyzable patients were all proven mismatch repair mutation carriers for LS (MLH1 = 33%, MSH2 = 47%, MSH6 = 15%, PMS2 = 4%, and EPCAM = 1%). The mean age (SD) was 40.5 (14.7) years, and 64 (46.4%) were men. The median withdrawal time for an NBI procedure was 8 minutes (interquartile range 6-11) compared with 13 minutes (interquartile range 8-17) for ICC. At least one adenoma was detected during the initial NBI pass in 28 patients (20.3%), and 42 patients (30.4%) had at least one adenoma detected after both NBI and ICC (difference, 10.1%; 95% confidence interval, -0.1%-20.3%); this represents an increase of 50.0% of the adenoma detection rate. ICC detected additional adenomas in 25 patients (18.1%).Colonoscopy combining NBI and ICC detects more adenomas than third-generation NBI alone in patients with LS, respectively, 30.4% vs 20.3% (difference, 10.1%; 95% confidence interval, -0.1 to 20.3), thus failing the noninferiority assumption of NBI compared with combined NBI and ICC. Although less time consuming, colonoscopy using the third-generation NBI cannot be recommended to replace ICC in patients with LS.

ObjectivesPrimary GI T-cell lymphoproliferative diseases (T-LPD) are heterogeneous entities, which raise difficult diagnosis and therapeutic challenges. We have recently provided evidences that lymphomas complicating coeliac disease (CD) arise from innate-like lymphocytes, which may carry NK receptors (NKRs).DesignNKRs expression was compared by flow cytometry in intraepithelial lymphocytes (IEL) from CD, type I or type II refractory CD (RCD). NKp46 was next assessed by immunohistochemistry in paraffin-embedded biopsies from 204 patients with CD, RCDI, RCDII or GI T-cell lymphomas and from a validation cohort of 61 patients. The cytotoxic properties of an anti-NKp46 monoclonal antibody conjugated to pyrrolobenzodiazepine (PBD) was tested ex vivo in human primary tumour cells isolated from fresh duodenal biopsies.ResultsNKp46 (but not CD94, NKG2A, NKG2C, NKG2D) was significantly more expressed by malignant RCDII IEL than by normal IEL in CD and RCDI. In paraffin biopsies, detection of >25 NKp46+ IEL per 100 epithelial cells discriminated RCDII from CD and RCDI. NKp46 was also detected in enteropathy-associated T-cell lymphomas (EATL, 24/29) and in monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL, 4/4) but not in indolent T-LPD (0/15). Treatment with anti-NKp46-PBD could efficiently and selectively kill human NKp46+ primary IEL ex vivo.ConclusionNKp46 is a novel biomarker useful for diagnosis and therapeutic stratification of GI T-LPD. Strong preclinical rationale identifies anti-NKp46-PBD as a promising therapy for RCDII, EATL and MEITL.

Background The feasibility of endoscopic submucosal dissection (ESD) in rectal tumors extending to the dentate line (RTDL) is unclear. Aims To analyze the outcomes of ESD in RTDL compared to non-RTDL, with a special focus on the lower rectum location. Methods Observational multicenter retrospective study. All patients with a rectal tumor who underwent ESD in 2013–2017 were included. A comparative analysis between RTDL and non-RTDL groups was done. Results Two-hundred and twenty-eight patients (median age: 69 years, range: 33–89, 51.3% male) with RTDL (n = 65, 28.5%) and non-RTDL lesions (n = 163, 71.5%) were included. There were no significant differences between the en-bloc (89.2% vs. 90.8%, p = 0.718), complete (60% vs. 71.8%, p = 0.084) and curative resection rates (58.5% vs. 68.7%, p = 0.141). The overall complication rate (4.6% vs. 8%, p = 0.370) was not different, independently of the rectal location. Local recurrence was higher in RTDL (7.3% vs. 1.5%, p = 0.065). The indication for surgery due to non-curative resections in the lower rectum was lower in RTDL (9.2% vs. 14.6%, p = 0.378). Conclusion The safety, effectiveness and long-term impact of ESD in RTDL and non-RTDLs is comparable. Local recurrence in the lower rectum may be higher in RTDL.

SummaryBackground Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. Aim To create a prognostic model to estimate survival of patients with refractory coeliac disease. Methods We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. Results The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11–63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38–3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22–6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61–0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. Conclusions Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up.

Cell sheet technology opens new perspectives in tissue regeneration therapy by providing readily implantable, scaffold-free 3D tissue constructs. Many studies have focused on the therapeutic effects of cell sheet implantation while relatively little attention has concerned the fate of the implanted cells in vivo. The aim of the present study was to track longitudinally the cells implanted in the cell sheets in vivo in target tissues. To this end we (i) endowed bone marrow-derived mesenchymal stem cells (BMMSCs) with imaging properties by double labeling with fluorescent and magnetic tracers, (ii) applied BMMSC cell sheets to a digestive fistula model in mice, (iii) tracked the BMMSC fate in vivo by MRI and probe-based confocal laser endomicroscopy (pCLE), and (iv) quantified healing of the fistula. We show that image-guided longitudinal follow-up can document both the fate of the cell sheet-derived BMMSCs and their healing capacity. Moreover, our theranostic approach informs on the mechanism of action, either directly by integration of cell sheet-derived BMMSCs into the host tissue or indirectly through the release of signaling molecules in the host tissue. Multimodal imaging and clinical evaluation converged to attest that cell sheet grafting resulted in minimal clinical inflammation, improved fistula healing, reduced tissue fibrosis and enhanced microvasculature density. At the molecular level, cell sheet transplantation induced an increase in the expression of anti-inflammatory cytokines (TGF-s2 and IL-10) and host intestinal growth factors involved in tissue repair (EGF and VEGF). Multimodal imaging is useful for tracking cell sheets and for noninvasive follow-up of their regenerative properties.