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INTRODUCTION: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is increasingly used in the setting of malignant gastric outlet obstruction (GOO). However, little is known about the role of primary EUS-GE. The aim of the present study is to compare the outcomes of EUS-GE by using the freehand technique as a first- and second-line approach after enteral stenting (ES). METHODS: This is an observational single-center study using a prospectively collected database. All consecutive patients who underwent an EUS-GE using the freehand technique due to malignant GOO were included. Patients with previous gastric surgery, a wire-guided EUS-GE technique, or those presenting without GOO were excluded. The primary outcome was the clinical success, defined as a solid oral intake at 1 week after the procedure (GOO Score, GOOSS ≥ 2). The secondary outcomes were technical success and adverse event (AE) rates. The impact on nutritional parameters was also assessed. RESULTS: Forty-five patients underwent an EUS-GE for all indications. Finally, 28 patients (mean age: 63 ± 17.2 years, 57.1% male) with (n = 13, 46.4%) and without (n = 15, 53.6%) a previous ES were included. The technical success was achieved in 25 cases (89.3%), with no differences between the two groups (92.3% vs. 86.7%, p = 1). The median limb diameter and procedure time were 27 mm (range:15-48) and 37 min. Overall, clinical success was achieved in 22 cases (88%), with three failures due to AEs (n = 2) or peritoneal carcinomatosis (n = 1). The diet progression was quicker in patients with a previous ES (GOOSS at 48 h, 2 vs. 1, p = 0.023), but the GOOSS at 1 week (p = 0.299), albumin gain (p = 0.366), and BMI gain (0.257) were comparable in the two groups. The AE rate was 7.1%. CONCLUSIONS: EUS-GE achieves a high technical and clinical success in patients with GOO regardless of the presence of a previous ES. Patients with previous ES may have a quicker progression of their diet, but the GOOSS and nutritional status in the long term at 1 week or 1 month are comparable. Primary EUS-GE might require fewer procedures and less discontinuation of chemotherapy to achieve a comparable result. ispartof: CANCERS vol:14 issue:22 ispartof: location:Switzerland status: published

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.

biodegradable stents of various designs are reportedly used in pancreato-biliary conditions with promising results. Their major advantage is the avoidance of repeat endoscopic procedure for stent removal, thereby reducing overall costs and endoscopic retrograde cholangiopancreatography (ERCP) associated adverse events. The aim of the study was to evaluate the feasibility and safety of a new biodegradable stent in patients with pancreato-biliary diseases.a prospective multicenter pilot study was performed. All consecutive patients ≥ 18 years old who underwent biliary or pancreatic stenting using the new biodegradable Archimedes stent were included in the study. There were three biodegradation profiles. Technical and clinical success and feasibility and safety were assessed during a pre-established follow-up schedule.fifty-three patients (mean age: 48.54 ± 19.29, 66 % male) with biliary (n = 29, 54.7 %) or pancreatic (n = 24, 45.3 %) indications were included. The distribution of stents used according to degradation properties were as follows: fast (n = 11, 20.8 %), medium (n = 16, 30.2 %) and slow (n = 26, 49.1 %). The technical and clinical success were 100 % and 77.8 %, respectively. Thirty-five patients were followed for a median of 26 weeks (range: 4-56, 66 %). There were nine procedure-related adverse events (17 %), all mild, including one uneventful stent-related event (external migration).the biodegradable Archimedes stent placement is feasible and safe in pancreato-biliary diseases.

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.

OBJECTIVES: Endoscopic ultrasound-guided digestive anastomosis (EUS-A) is a new alternative under evaluation in patients presenting with afferent limb syndrome (ALS) after Whipple surgery. The aim of the present study is to analyze the safety and effectiveness of EUS-A in ALS. METHODS: This is an observational multicenter study. All patients ≥18 years old with previous Whipple surgery presenting with ALS who underwent an EUS-A using a lumen-apposing metal stent (LAMS) between 2015 and 2021 were included. The primary outcome was clinical success, defined as resolution of the ALS or ALS-related cholangitis. Furthermore, technical success, adverse event rate, and mortality were evaluated. RESULTS: Forty-five patients (mean age: 65.5 ± 10.2 years; 44.4% male) were included. The most common underlying disease was pancreatic cancer (68.9%). EUS-A was performed at a median of 6 weeks after local tumor recurrence. The most common approach used was the direct/freehand technique (66.7%). Technical success was achieved in 95.6%, with no differences between large (≥15 mm) and small LAMS (97.4% vs. 100%, P = 0.664). Clinical success was retained in 91.1% of patients. A complementary treatment by dilation of the stent followed by endoscopic retrograde cholangiopancreatography through the LAMS was performed in three cases (6.7%). There were six recurrent episodes of cholangitis (14.6%) and two procedure-related adverse events (4.4%) after a median follow-up of 4 months. Twenty-six patients (57.8%) died during the follow-up due to disease progression. CONCLUSION: EUS-A is a safe and effective technique in the treatment of malignant ALS, achieving high clinical success with an acceptable recurrence rate. ispartof: DIGESTIVE ENDOSCOPY vol:34 issue:7 pages:1433-1439 ispartof: location:Australia status: published

Background. In case of high risk of lymph node invasion after endoscopic resection (ER) of superficial esophageal squamous cell carcinoma (SCC), adjuvant chemoradiotherapy (CRT) can be an alternative to surgery. We assessed long-term clinical outcomes of adjuvant therapy by CRT after non-curative ER for superficial SCC. Methods. We performed a retrospective multicenter study. From April 1999 to April 2018, all consecutive patients who underwent ER for SCC with tumor infiltration beyond the muscularis mucosae were included. Results. A total of 137 ER were analyzed. The overall nodal or metastatic recurrence-free survival rate at 5 years was 88% and specific recurrence-free survival rates at 5 years with and without adjuvant therapy were, respectively, 97.9% and 79.1% (p = 0.011). Independent factors for nodal and/or distal metastatic recurrence were age (HR = 1.075, p = 0.031), Sm infiltration depth > 200 µm (HR = 4.129, p = 0.040), and the absence of adjuvant CRT or surgery (HR = 11.322, p = 0.029). Conclusion. In this study, adjuvant therapy is associated with a higher recurrence-free survival rate at 5 years after non-curative ER. This result suggests this approach may be considered as an alternative to surgery in selected patients.

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.

The aim of our study was to compare clear liquid diet with 2 different polyethylene glycol (PEG)-based bowel preparation methods regarding diagnostic yield of small bowel capsule endoscopy (SBCE) in patients with suspected small bowel bleeding (SBB).In this prospective multicenter randomized controlled trial, consecutive patients undergoing SBCE for suspected SBB between September 2010 and February 2016 were considered. Patients were randomly assigned to standard regimen, that is, clear fluids only (prep 1), standard regimen plus 500 mL PEG after SBCE ingestion (prep 2), or standard regimen plus 2 L PEG plus 500 mL PEG after SBCE ingestion (prep 3). The primary outcome was the detection of at least one clinically significant lesion in the small bowel. The quality of small bowel cleansing was assessed. A questionnaire on the clinical tolerance was filled by the patients.We analyzed 834 patients. No significant difference was observed for detection of P1 or P2 small bowel lesions between prep1 group (40.5%), prep 2 group (40.2%), and prep 3 group (38.5%). Small bowel cleansing was improved in prep 2 and 3 groups compared with that in prep 1 group. Compliance to the preparation and tolerance was better in prep 2 group than in prep 3 group.Small bowel purgative before SBCE allowed better quality of cleansing. However, it did not improve diagnostic yield of SBCE for suspected SBB.

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.

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/mAcid 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.

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