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PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition.We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction.We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77-0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression.The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection.

Main Recommendations MR1 ESGE recommends small-bowel capsule endoscopy as the first-line examination, before consideration of other endoscopic and radiological diagnostic tests for suspected small-bowel bleeding, given the excellent safety profile of capsule endoscopy, its patient tolerability, and its potential to visualize the entire small-bowel mucosa.Strong recommendation, moderate quality evidence. MR2 ESGE recommends small-bowel capsule endoscopy in patients with overt suspected small-bowel bleeding as soon as possible after the bleeding episode, ideally within 48 hours, to maximize the diagnostic and subsequent therapeutic yield.Strong recommendation, high quality evidence. MR3 ESGE does not recommend routine second-look endoscopy prior to small-bowel capsule endoscopy in patients with suspected small-bowel bleeding or iron-deficiency anemia.Strong recommendation, low quality evidence. MR4 ESGE recommends conservative management in those patients with suspected small-bowel bleeding and high quality negative small-bowel capsule endoscopy.Strong recommendation, moderate quality evidence. MR5 ESGE recommends device-assisted enteroscopy to confirm and possibly treat lesions identified by small-bowel capsule endoscopy.Strong recommendation, high quality evidence. MR6 ESGE recommends the performance of small-bowel capsule endoscopy as a first-line examination in patients with iron-deficiency anemia when small bowel evaluation is indicated.Strong recommendation, high quality evidence. MR7 ESGE recommends small-bowel capsule endoscopy in patients with suspected Crohn’s disease and negative ileocolonoscopy findings as the initial diagnostic modality for investigating the small bowel, in the absence of obstructive symptoms or known bowel stenosis.Strong recommendation, high quality evidence. MR8 ESGE recommends, in patients with unremarkable or nondiagnostic findings from dedicated small-bowel cross-sectional imaging, small-bowel capsule endoscopy as a subsequent investigation if deemed likely to influence patient management.Strong recommendation, low quality evidence. MR9 ESGE recommends, in patients with established Crohn’s disease, the use of a patency capsule before small-bowel capsule endoscopy to decrease the capsule retention rate.Strong recommendation, moderate quality evidence. MR10 ESGE recommends device-assisted enteroscopy (DAE) as an alternative to surgery for foreign bodies retained in the small bowel requiring retrieval in patients without acute intestinal obstruction.Strong recommendation, moderate quality evidence. MR11 ESGE recommends DAE-endoscopic retrograde cholangiopancreatography (DAE-ERCP) as a first-line endoscopic approach to treat pancreaticobiliary diseases in patients with surgically altered anatomy (except for Billroth II patients).Strong recommendation, moderate quality evidence.

Background Motorized spiral enteroscopy (MSE) has been shown to be safe and effective for deep enteroscopy in studies performed at expert centers with limited numbers of patients without previous abdominal surgery. This study aimed to investigate the safety, efficacy, and learning curve associated with MSE in a real-life scenario, with the inclusion of patients after abdominal surgery and with altered anatomy. Methods Patients with indications for deep enteroscopy were enrolled in a prospective observational multicenter study. The primary objective was the serious adverse event (SAE) rate; secondary objectives were the diagnostic and therapeutic yield, procedural success, time, and insertion depth. Data analysis was subdivided into training and core (post-training) study phases at centers with different levels of MSE experience. Results 298 patients (120 women; median age 68, range 19–92) were enrolled. In the post-training phase, 21.5 % (n = 54) had previous abdominal surgery, 10.0 % (n = 25) had surgically altered anatomy. Overall, SAEs occurred in 2.3 % (7/298; 95 %CI 0.9 %–4.8 %). The SAE rate was 2.0 % (5/251) in the core group and 4.3 % (2/47) in the training group, and was not increased after abdominal surgery (1.9 %). Total enteroscopy was achieved in half of the patients (n = 42) undergoing planned total enteroscopy. In 295/337 procedures (87.5 %), the anatomical region of interest could be reached. Conclusions This prospective multicenter study showed that MSE was feasible and safe in a large cohort of patients in a real-life setting, after a short learning curve. MSE was shown to be feasible in postsurgical patients, including those with altered anatomy, without an increase in the SAE rate.

International audience; Only a few patients with germline AXIN2 variants and colorectal adenomatous polyposis or cancer have been described, raising questions about the actual contribution of this gene to colorectal cancer (CRC) susceptibility. To assess the clinical relevance for AXIN2 testing in patients suspected of genetic predisposition to CRC, we collected clinical and molecular data from the French Oncogenetics laboratories analyzing AXIN2 in this context. Between 2004 and June 2020, 10 different pathogenic/likely pathogenic AXIN2 variants were identified in 11 unrelated individuals. Eight variants were from a consecutive series of 3322 patients, which represents a frequency of 0.24%. However, loss‐of‐function AXIN2 variants were strongly associated with genetic predisposition to CRC as compared with controls (odds ratio: 11.89, 95% confidence interval: 5.103–28.93). Most of the variants were predicted to produce an AXIN2 protein devoid of the SMAD3‐binding and DIX domains, but preserving the β‐catenin‐binding domain. Ninety‐one percent of the AXIN2 variant carriers who underwent colonoscopy had adenomatous polyposis. Forty percent of the variant carriers developed colorectal or/and other digestive cancer. Multiple tooth agenesis was present in at least 60% of them. Our report provides further evidence for a role of AXIN2 in CRC susceptibility, arguing for AXIN2 testing in patients with colorectal adenomatous polyposis or cancer.

Background and study aims Prophylactic surgery of familial adenomatous polyposis (FAP) includes total colectomy with ileorectal anastomosis (IRA) to proctocolectomy with ileoanal anastomosis (IAA). Surgical guidelines rely on studies without systematic endoscopic follow-up and treatment. Our aim was to report our experience based on a different approach: therapeutic follow-up, comparing in this setting IRA and IAA in terms of oncological safety and quality of life. Patients and methods Between January 1965 and November 2015, all patients who underwent prophylactic surgery for FAP with therapeutic endoscopic follow-up in Lyon University hospital: systematic endoscopic treatment of adenomas, were retrospectively and prospectively (since 2011) included. Results A total of 296 patients were analyzed: 92 had proctocolectomy with IAA (31.1 %), 197 total colectomy with IRA (66.5 %), and seven abdominoperineal resections (2.4 %). Median follow-up was 17.1 years (range, 0–38.1). Incidence of secondary cancer (IR vs. IAA) was 6.1 % vs. 1.1 % (P = 0.06; 95 %CI 0.001–0.36). The 15-year cancer-free and overall survival (IR vs. IAA) were 99.5 % vs 100 % (P = 0.09) and 98.9 % vs. 98.8 % (P = 0.82), respectively. Postoperative morbidity occurred in 44 patients: 29 (14.7 %) in the IRA and 15 (16.3 %) in the IAA group (P = 0.72). The mean number of stools per day in the respective groups were 4.4 (2.5) vs. 5.5 (2.6) (P = 0.001). Fecal incontinence occurred in 14 patients (7.1 %) in the IRA vs. 16 (17.4 %) in the IAA group (P = 0.03). Conclusions A combination of therapeutic endoscopic treatment and extended rectal preservation appears to be a safe alternative to ileoanal J-pouch anastomosis.

Background Superficial oesophageal adenocarcinoma can be resected endoscopically, but data to define a curative endoscopic resection are scarce. Objective Our study aimed to assess the risk of lymph node metastasis depending on the depth of invasion and histological features of oesophageal adenocarcinoma. Methods We retrospectively included all patients undergoing an endoscopic resection for T1 oesophageal adenocarcinoma among seven expert centres in France in 2004–2016. Mural invasion was defined as either intramucosal or submucosal tumours; the latter were further divided into superficial submucosal (1000 mm). Absence or presence of lymphovascular invasion and/or poorly differentiated cancer (G3) defined a low‐risk or a high‐risk tumour, respectively. For submucosal tumours, invasion depth and histological features were systematically confirmed after a second dedicated histological assessment (new 2‐mm thick slices) performed by a second pathologist. Occurrence of lymph node metastasis was recorded during the follow‐up from histological or PET CT reports when an invasive procedure was not possible. Results In total, 188 superficial oesophageal adenocarcinomas were included with a median follow‐up of 34 months. No lymph node metastases occurred for intramucosal oesophageal adenocarcinomas (n = 135) even with high‐risk histological features. Among submucosal oesophageal adenocarcinomas, only tumours with lymphovascular invasion or poorly differentiated cancer or with a depth of invasion >1000 μm developed lymph node metastasis tumours (n = 10/53%; 18.9%; hazard ratio 12.04). No metastatic evolution occurred under a 1000‐mm threshold for all low‐risk tumours (0/25), nor under 1200 mm (0/1) and three over this threshold (3/13%, 23.1%). Conclusion Intramucosal and low‐risk tumours with shallow submucosal invasion up to 1200 mm were not associated with lymph node metastasis during follow‐up. In case of high‐risk features and/or deep submucosal invasion, endoscopic resections are not sufficient to eliminate the risk of lymph node metastasis, and surgical oesophagectomy should be carried out. These results must be confirmed by larger prospective series., Key Summary Superficial oesophageal adenocarcinoma (OAC) can be resected endoscopically.Data to define a curative endoscopic resection with a low lymph node metastasis (LNM) risk are scarce especially for tumours invading the submucosa.Curative endoscopic resections have been reported in selected OAC invading the first 500 mm of the submucosa, but surgical series showed an LNM risk ranging from 0% to 50%, making endoscopic resection a questionable curative treatment.High‐risk histological features were not associated with LNM in intramucosal tumours.LNM occurred only for tumours invading the submucosa with a depth ≥1200 mm or with high‐risk histological features regardless of the depth of invasion.Endoscopic resection may be a valid and curative therapeutic option for all intramucosal tumours and for submucosal oesophageal adenocarcinoma with an invasion depth ≤1000 mm and low‐risk histological features.

International audience; Introduction: Desmoid tumor (DT) of the abdomen is a challenging and rare disease. The level of evidence available to document their treatment is relatively low, however, recent publications of prospective studies have allowed to precise their management.Methods: This document is a summary of the French intergroup guidelines realized by all French medical and surgical societies involved in the management of DT located in the abdomen or associated with adenomatous polyposis. Recommendations are graded in four categories (A, B, C and D), according to the level of evidence found in the literature until January 2021.Results: When the diagnosis of DT is suspected a percutaneous biopsy should be performed when possible. A molecular analysis looking for pathogenic mutations of the CTNNB1 and APC genes should be systematically performed. When a somatic pathogenic variant of the APC gene is present, an intestinal polyposis should be searched. Due to a high rate of spontaneous regression, non-complicated DT should first benefit from an active surveillance with MRI within 2 months after diagnosis to assess the dynamic of tumor growth. The treatment decision must be discussed in an expert center, favoring the less toxic treatments which can include broad spectrum tyrosine kinase inhibitor or conventional chemotherapy (methotrexate-vinblastine). Surgery, outside the context of emergency, should only be considered for favorable location in an expert center.Conclusion: French guidelines for DT management were elaborated to help offering the best personalized therapeutic strategy in daily clinical practice as the DT therapeutic landscape is complexifying. Each individual case must be discussed within a multidisciplinary expert team.

Performance of endoscopic procedures is associated with a risk of infection from COVID-19. This risk can be reduced by the use of personal protective equipment (PPE). However, shortage of PPE has emerged as an important issue in managing the pandemic in both traditionally high and low-resource areas. A group of clinicians and researchers from thirteen countries representing low, middle, and high-income areas has developed recommendations for optimal utilization of PPE before, during, and after gastrointestinal endoscopy with particular reference to low-resource situations. We determined that there is limited flexibility with regard to the utilization of PPE between ideal and low-resource settings. Some compromises are possible, especially with regard to PPE use, during endoscopic procedures. We have, therefore, also stressed the need to prevent transmission of COVID-19 by measures other than PPE and to conserve PPE by reduction of patient volume, limiting procedures to urgent or emergent, and reducing the number of staff and trainees involved in procedures. This guidance aims to optimize utilization of PPE and protection of health care providers.

A typical capsule endoscopy (CE) case generates tens of thousands of images, with abnormalities often confined to a just few frames. Omni Mode is a novel EndoCapsule software algorithm (Olympus, Tokyo, Japan) that proposes to intelligently remove duplicate images while maintaining accuracy in lesion detection.This prospective multicenter study took place across 9 European centers. Consecutive, unselected CE cases were read conventionally in normal mode, with every captured frame reviewed. Cases were subsequently anonymized and randomly allocated to another center where they were read using Omni Mode. Detected lesions and reading times were recorded, with findings compared between both viewing modes. The clinical significance of lesions was described according to the P classification (P0, P1, and P2). Where a discrepancy in lesion detection in either mode was found, expert blinded review at a consensus meeting was undertaken.The patient population undergoing CE had a mean age of 49.5 years (range, 18-91), with the investigation of anemia or GI bleeding accounting for 71.8% of cases. The average small-bowel transit time was 4 hours, 26 minutes. The mean reading time in normal mode was 42.5 minutes. The use of Omni Mode was significantly faster (P .0001), with an average time saving of 24.6 minutes (95% confidence interval, 22.8-26.9). The 2127 lesions were identified and classified according to the P classification as P0 (1234), P1 (656), and P2 (237). Lesions were identified using both reading modes in 40% (n = 936), and 1186 lesions were identified by either normal or Omni Mode alone. Normal mode interpretation was associated with 647 lesions being missed, giving an accuracy of .70. Omni Mode interpretation led to 539 lesions being missed, with an accuracy of .75. There was no significant difference in clinical conclusions made between either reading mode.This study shows that CE reading times can be reduced by an average of 40%, without any reduction in clinical accuracy.

Background Gastric hyperplastic polyps (GHPs) have a risk of neoplastic transformation reaching 5 %. Current endoscopic resection techniques appear suboptimal with a high risk of local recurrence. This study assessed the outcomes of endoscopic resection for GHPs and identified risk factors for recurrence and neoplastic transformation. Methods This retrospective, multicenter, European study included adult patients with at least one GHP ≥ 10 mm who underwent endoscopic resection and at least one follow-up endoscopy. Patients with recurrent GHPs or hereditary gastric polyposis were excluded. All data were retrieved from the endoscopy, pathology, and hospitalization reports. Results From June 2007 to August 2018, 145 GHPs in 108 patients were included. Recurrence after endoscopic resection was 51.0 % (74 /145) in 55 patients. R0 resection or en bloc resection did not impact the risk of polyp recurrence. In multivariate analysis, cirrhosis was the only risk factor for recurrence (odds ratio [OR] 4.82, 95 % confidence interval [CI] 1.33 – 17.46; P = 0.02). Overall, 15 GHPs (10.4 %) showed neoplastic transformation, with size > 25 mm (OR 10.24, 95 %CI 2.71 – 38.69; P Conclusions Results confirmed the risk of recurrence and neoplastic transformation of large GHPs. The risk of neoplastic change was significantly increased for lesions > 25 mm, with a risk of high grade dysplasia appearing in polyps ≥ 50 mm. The risk of recurrence was high, particularly in cirrhosis patients, and long-term follow-up is recommended in such patients.

Background Endoscopic submucosal dissection (ESD) of residual or locally recurrent (RLR) colonic lesions after previous endoscopic mucosal resection (EMR) is an attractive but challenging technique. The present study aimed to evaluate the effectiveness and safety of ESD with double clip and rubber band traction (DCT-ESD) of RLR colonic lesions. Methods We retrospectively analyzed all consecutive DCT-ESD procedures for RLR colonic lesions (rectum excluded) performed in two French centers. The frequency of en bloc and R0 resections, procedure speed, additional surgery, and complications were evaluated. R0 resection was also used to investigate the learning curve. Results Among the 53 resections, 49 (92.5 %) were performed en bloc and 42 (79.2 %) achieved R0. The median procedure speed was 21 mm2/min. There were four (7.5 %) intraoperative perforations and one delayed bleeding; these were successfully treated endoscopically. There was no salvage surgery for complications. The R0 rate increased from 16/26 (61.5 %) for the first 26 procedures to 26/27 (96.3 %, P = 0.002) for the last 27 procedures. Conclusions DCT-ESD appears to be a safe and effective treatment for RLR colonic lesions after EMR.

Mechanisms of drug-tolerance remain poorly understood and have been linked to genomic but also to non-genomic processes. 5-fluorouracil (5-FU), the most widely used chemotherapy in oncology is associated with resistance. While prescribed as an inhibitor of DNA replication, 5-FU alters all RNA pathways. Here, we show that 5-FU treatment leads to the production of fluorinated ribosomes exhibiting altered translational activities. 5-FU is incorporated into ribosomal RNAs of mature ribosomes in cancer cell lines, colorectal xenografts, and human tumors. Fluorinated ribosomes appear to be functional, yet, they display a selective translational activity towards mRNAs depending on the nature of their 5′-untranslated region. As a result, we find that sustained translation of IGF-1R mRNA, which encodes one of the most potent cell survival effectors, promotes the survival of 5-FU-treated colorectal cancer cells. Altogether, our results demonstrate that “man-made” fluorinated ribosomes favor the drug-tolerant cellular phenotype by promoting translation of survival genes., Different mechanisms have been reported to explain resistance to chemotherapy in cancer. Here, the authors show that the chemotherapeutic drug 5-fluorouracil alters the function of ribosomes to promote pro-survival gene translation leading to chemotherapy resistance.

Juvenile polyposis represents an heterogeneous disease as different genetic dominant backgrounds have been evidenced leading to different clinical presentations. It is associated in some patients with a different syndrome, Hereditary Hemorragic Telangiectasia, justifying a complementary and different management. Recent international recommendations help in managing this very rare disease, and this management should probably be restricted to expert centers able to take care of the multiple manifestations and risks of these patients and families. This paper will focus on the poorly known and evaluated aspects of juvenile polyposis, excluding the colonic involvement and epidemiology that are addressed in a different article of this issue.

Current evidence suggests that 30–50% of cancers are attributable to established lifestyle risk factors. Cancer-screening has been identified as an opportunity for delivering advice on lifestyle behaviour change for cancer prevention. This study aimed to evaluate the feasibility and acceptance of promoting advice on the latest evidence-based lifestyle recommendations for cancer prevention at the time of colorectal cancer screening at two hospitals in Lyon, France. This feasibility study included 49 patients (20 men and 29 women) who were invited for colonoscopy. Patients received a leaflet with lifestyle recommendations for cancer prevention, accompanied with a logbook to plan and monitor their behavioural changes. Feedback from patients, hospital staff, and researchers was received via evaluation questionnaires (n = 26) completed after testing the educational material for at least two weeks and via two focus group discussions (n = 7 and n = 9 respectively) organized at the end of the study. All interviewed patients were interested in lowering their cancer risk, and the majority felt ready to change their lifestyle (88%), although most did not know how to decrease their risk of cancer (61%). All patients found the educational material easy to understand and sufficiently attractive and 50% of the patients reported having achieved at least one of the healthy behaviours recommended within the two weeks following the intervention. All hospital staff and almost all patients (92%) involved found that the screening program and the visits planned for colonoscopy was an appropriate moment to provide them with the educational material. This feasibility study has shown that the content, paper-based format, and time of delivery of the intervention were adequate. Health professionals seem to be willing to provide lifestyle recommendations, and patients appear interested in receiving advice for lowering their cancer risk during screening visits.

Climate change has been described as the biggest global health threat of the 21st century1 and has significant implications for gastrointestinal (GI) health and disease,2 which is the focus of this consensus commentary provided by the World Gastroenterology Organisation (WGO) Climate Change Working Group (CCWG). The CCWG has members from 18 countries representing high-income, medium-income and low-income populations. The WGO includes gastroenterology societies from 108 countries, which represent more than 60 000 medical practitioner members. The CCWG members, who have coauthored this consensus commentary, aim to review the scientific literature on climate and GI health, to encourage education and the undertaking of actionable measures including advocacy, and to further research and collaborations within the global GI community. The CCWG’s objective is to assist GI health providers worldwide to adapt to, and mitigate, the effects of climate change on health. The CCWG has partnered with three major GI journals, which are copublishing this commentary, given the timeliness and importance of the topic.3 4 ### Climate change The earth’s climate is changing because of increasing concentrations of greenhouse gases in the atmosphere, which has already warmed by more than 1°C compared with preindustrial times. The aim of mitigation efforts is to keep the rise in global mean surface temperature (GMST) below 2°C by 2100. An increase of 2°C might not seem like a major change, but variations of similar magnitude have been associated with profound alterations of climate in the past. It is important to note that even if this somewhat arbitrary target can be met, catastrophic changes in earth ecosystems can still occur. The Intergovernmental Panel on Climate Change was established in 1988 with a mandate to assess relevant scientific literature related to climate change. It produces regular reports and updates about climate change. The Intergovernmental Panel on Climate Change projects that …

Partial response to chemotherapy leads to disease resurgence. Upon treatment, a subpopulation of cancer cells, called drug-tolerant persistent cells, display a transitory drug tolerance that lead to treatment resistance 1,2. Though drug-tolerance mechanisms remain poorly known, they have been linked to non-genomic processes, including epigenetics, stemness and dormancy 2–4. 5-fluorouracil (5-FU), the most widely used chemotherapy in cancer treatment, is associated with resistance. While prescribed as an inhibitor of DNA replication, 5-FU alters all RNA pathways 5–9. Here, we show that 5-FU treatment leads to the unexpected production of fluorinated ribosomes, exhibiting altered mRNA translation. 5-FU is incorporated into ribosomal RNAs of mature ribosomes in cancer cell lines, colorectal xenografts and human tumours. Fluorinated ribosomes appear to be functional, yet, they display a selective translational activity towards mRNAs according to the nature of their 5’-untranslated region. As a result, we found that sustained translation of IGF-1R mRNA, which codes for one of the most potent cell survival effectors, promoted the survival of 5-FU-treated colorectal cancer cells. Altogether, our results demonstrate that “man-made” fluorinated ribosomes favour the drug-tolerant cellular phenotype by promoting translation of survival genes. This could be exploited for developing novel combined therapies. By unraveling translation regulation as a novel gene expression mechanism helping cells to survive a drug-challenge, our study extends the spectrum of molecular mechanisms driving drug-tolerance.

International audience; Background and aimsCurrent artificial intelligence (AI)-based solutions for capsule endoscopy (CE) interpretation are proprietary. We aimed to evaluate an AI solution trained on a specific CE system (Pillcam®, Medtronic) for the detection of angiectasias on images captured by a different proprietary system (MiroCam®, Intromedic).Material and methodsAn advanced AI solution (Axaro®, Augmented Endoscopy), previously trained on Pillcam® small bowell images, was evaluated on independent datasets with more than 1200 Pillcam® and MiroCam® still frames (equally distributed, with or without angiectasias). Images were reviewed by experts before and after AI interpretation.ResultsSensitivity for the diagnosis of angiectasia was 97.4% with Pillcam® images and 96.1% with Mirocam® images, with specificity of 98.8% and 97.8%, respectively. Performances regarding the delineation of regions of interest and the characterization of angiectasias were similar in both groups (all above 95%). Processing time was significantly shorter with Mirocam® (20.7 ms) than with Pillcam® images (24.6 ms, p

Background and study aims Colon capsule endoscopy (CCE) has been proposed as an alternative to colonoscopy for screening patients at average risk of colorectal cancer (CRC). A prospective national cohort was developed to assess relevance of CCE in real-life practice and its short- and long-term impacts on clinical management. Patients and methods All patients who underwent a CCE in France were prospectively enrolled from January 2011 to May 2016 and reached annually by phone until May 2017. All CCE and colonoscopy reports were systematically collected. Results During the study period, 689 CCEs were analyzed from 14 medical centers. Median follow-up time was 35 months [IQR: 12–50]. Indication for CCE was mainly for elderly patients (median age: 70 years, IQR: [61–79]) due to anesthetic or colonoscopy contraindication (n = 307; 44.6 %). Only 337 CCEs (48.9 %) were both complete and with adequate bowel preparation. Advanced neoplasia (adenoma with high-grade dysplasia or CRC) was diagnosed following 32 CCEs (4.6 %). Among patients who underwent colonoscopy or therapeutic surgery following CCE, 18.8 % of all advanced neoplasias (6/32) had not been diagnosed by CCE mainly due to technical issues. Performing a colonoscopy in the case of significant polyps or insufficient bowel cleansing or after an incomplete CCE allowed the diagnosis of 96.9 % of all identified advanced neoplasias (31/32). Conclusions Outside the scope of academic trials, improvement is needed to increase the reliability of CCE as less than half were considered optimal i. e. complete with adequate bowel cleansing. Most of missed colonic advanced neoplasia were due to incomplete CCE with distal neoplasia location.

5-Fluorouracil (5-FU) is a chemotherapeutic drug widely used to treat patients with solid tumours, such as colorectal and pancreatic cancers. Colorectal cancer (CRC) is the second leading cause of cancer-related death and half of patients experience tumour recurrence. Used for over 60 years, 5-FU was long thought to exert its cytotoxic effects by altering DNA metabolism. However, 5-FU mode of action is more complex than previously anticipated since 5-FU is an extrinsic source of RNA modifications through its ability to be incorporated into most classes of RNA. In particular, a recent report highlighted that, by its integration into the most abundant RNA, namely ribosomal RNA (rRNA), 5-FU creates fluorinated active ribosomes and induces translational reprogramming. Here, we review the historical knowledge of 5-FU mode of action and discuss progress in the field of 5-FU-induced RNA modifications. The case of rRNA, the essential component of ribosome and translational activity, and the plasticity of which was recently associated with cancer, is highlighted. We propose that translational reprogramming, induced by 5-FU integration in ribosomes, contributes to 5-FU-driven cell plasticity and ultimately to relapse., Graphical Abstract Graphical Abstract5-FU integration in ribosomes contributes to cell plasticity through translational reprogramming.

Main RecommendationsESGE recommends that individuals with hereditary gastrointestinal polyposis syndromes should be surveilled in dedicated units that provide monitoring of compliance and endoscopic performance measures. Strong recommendation, moderate quality of evidence, level of agreement 90 %.ESGE recommends performing esophagogastroduodenoscopy, small-bowel examination, and/or colonoscopy earlier than the planned surveillance procedure if a patient is symptomatic. Strong recommendation, low quality of evidence, level of agreement 100 %.

Background and Aim The diagnostic evaluation and management of patients with chronic dyspepsia may differ geographically according to patient age, prevalence of Helicobacter pylori or parasitic infection, and risk of gastric cancer. The characteristics and appropriate investigation of Cambodian patients with dyspepsia have not previously been studied. The aim of this study was to investigate the characteristics of Cambodian patients with chronic dyspepsia, the yield of upper endoscopy in these patients, and the value of alarm features in identifying patients with organic causes of dyspepsia. Methods We conducted a retrospective, single‐center study of 1231 adults with chronic dyspepsia who underwent upper endoscopy. We compared clinical characteristics, H. pylori prevalence, and endoscopic and histological findings of patients with functional or organic causes of dyspepsia. This study was approved by the National Ethics Committee for Health Research. Results The majority of patients had overlapping symptoms of epigastric pain/burning and postprandial fullness/early satiety (40.6%), followed by epigastric pain/burning alone (29.7%) and postprandial fullness/early satiety alone (29.7%). Organic lesions were diagnosed in 6.9% of patients. The overall prevalence of H. pylori infection was 46% and was similar in the three clinical subgroups. The sensitivity and specificity of alarm features for organic causes of dyspepsia were 14 and 96%, respectively. The majority of patients with gastric cancer were 40 years of age or older. Conclusions The majority of patients with chronic dyspepsia seen at our outpatient center were diagnosed with functional or H. pylori‐associated dyspepsia. The presence of alarm features was not sensitive or specific for differentiating organic and functional dyspepsia., This paper is the first to describe the clinical and endoscopic correlates of patients with dyspepsia in Cambodia, including predictors for organic causes of dyspepsia such as peptic ulcer disease or gastric cancer. The results are synthesized into a proposed algorithm for the management of dyspepsia in Cambodia.

The European Society of Gastrointestinal Endoscopy (ESGE) together with the United European Gastroenterology (UEG) recently developed a short list of performance measures for small-bowel endoscopy (i.e. small-bowel capsule endoscopy and device-assisted enteroscopy) with the final goal of providing endoscopy services across Europe with a tool for quality improvement. Six key performance measures both for small-bowel capsule endoscopy and for device-assisted enteroscopy were selected for inclusion, with the intention being that practice at both a service and endoscopist level should be evaluated against them. Other performance measures were considered to be less relevant, based on an assessment of their overall importance, scientific acceptability, and feasibility. Unlike lower and upper gastrointestinal endoscopy, for which performance measures had already been identified, this is the first time small-bowel endoscopy quality measures have been proposed. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:7 issue:5 pages:614-641 ispartof: location:England status: published

Purpose of review Benign small bowel polyps or mass are clinically poorly distinguishable from malignant small bowel masses, and the diagnostic conditions are almost the same. The important point for clinicians is first to take advantage of the different available diagnostic tools to optimize the diagnostic algorithm of a small bowel polyp or mass. Next, according to the clinical situation, associated disease or sporadic situation, the difficulty is to adapt the treatment decision to the patient situation. Recent findings The last 20 years have been marked by the development of major diagnostic tools for small bowel diseases (capsule endoscopy, cross-sectional imaging with enteroclysis and balloon-assisted enteroscopy) and by the major decrease of intra-operative enteroscopy as a diagnostic mean. Summary On the basis of considerable development of capsule endoscopy and the improvement of cross-sectional small bowel imagining, small bowel polyps represent now a frequent clinical situation for gastroenterologists.

Liver transplantation (LT) has been proposed as a curative treatment in hereditary hemorrhagic telangiectasia (HHT) with severe hepatic involvement. We provide a long-term evaluation of graft status after LT for HHT, with a focus on the risk of recurrence. The present study included all patients prospectively followed up after LT for HHT in the Lyon Liver Transplant Unit from 1993 to 2010, with a survival of more than 1 year. Protocol clinical, radiological, and histological examinations were performed at regular intervals. Fourteen patients were included (13 women and one man). Median age at LT was 52.5 years (range: 33.1-66.7). In eight patients (seven female), disease recurrence was diagnosed by abnormal radiological features, suggestive of microcirculatory disturbances. Typical vascular lesions, including telangiectasia, were demonstrated by liver biopsy in five of these patients. The median interval between LT and diagnosis of recurrence was 127 months (range: 74-184). The risk of recurrence increased over time; estimated cumulative risk was 47.9% at 15 years. Liver tissue analysis found the coexistence of an angiogenic process combined with endothelial microchimerism, as shown by the presence of vascular lining cells of recipient origin. Conclusion: The present data show that disease recurrence occurs, usually after a long delay, in a significant number of patients treated by LT for liver complications of HHT. This strongly supports the necessity of a lifelong follow-up and suggests that therapeutic strategy needs discussion and evaluation, especially of the role of potential adjuvant treatments to LT, such as antiangiogenic medications, when recurrent disease appears.

Background and study aims Nomenclature and descriptions of small bowel (SB) vascular lesions in capsule endoscopy (CE) are scarce in the medical literature. They are mostly based on the reader's opinion and thus differ between experts, with a potential negative impact on clinical care, teaching and research regarding SBCE. Our aim was to better define a nomenclature and to give a description of the most frequent vascular lesions in SBCE. Methods A panel of 18 European expert SBCE readers was formed during the UEGW 2016 meeting. Three experts constructed an Internet-based four-round Delphi consensus, but did not participate in the voting process. They built questionnaires that included various still frames of vascular lesions obtained with a third-generation SBCE system. The 15 remaining participants were asked to rate different proposals and description of the most common SB vascular lesions. A 6-point rating scale (varying from ‘strongly disagree’ to ‘strongly agree’) was used successive rounds. The consensus was reached when at least 80 % voting members scored the statement within the ‘agree’ or ‘strongly agree’. Results Consensual terms and descriptions were reached for angiectasia/angiodysplasia, erythematous patch, red spot/dot, and phlebectasia. A consensual description was reached for more subtle vascular lesions tentatively named “diminutive angiectasia” but no consensus was reached for this term. Conclusion An international group has reached a consensus on the nomenclature and descriptions of the most frequent and relevant SB vascular lesions in CE. These terms and descriptions are useful in daily practice, for teaching and for medical research purposes.

Simple Summary Lynch syndrome is characterized by a higher relative risk of developing certain cancers, especially digestive cancers. Many guidelines from different scientific societies are now available and allow excellent follow-up for these patients, but occasionally propose divergent management approaches. We provide here a synthesis of these guidelines and a focus on prevention, diagnosis, and endoscopic follow-up of these digestive cancers and early neoplasia. Abstract Lynch syndrome patients could benefit from various recommendations to prevent digestive cancers. In this review, we summarize the criteria to identify Lynch syndrome in patients with digestive cancers. We detail endoscopic screening procedures in patients with Lynch syndrome for gastric, small bowel, pancreatic, and colorectal cancers. We review the precise modalities of endoscopic follow-up, particularly the discrepancies that exist between the guidelines of the various scientific societies. We discuss the treatment of colorectal cancers in Lynch syndrome cases and patient adherence to endoscopic follow-up programs.

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.

Background and aims: Current guidelines recommend colonoscopy every 3–5 years for colorectal cancer (CRC) screening of individuals with a familial history of CRC. The objective of this study was to compare the cost effectiveness of screening alternatives in this population. Methods: Eight screening strategies were compared with no screening: fecal immunochemical test (FIT), Stool DNA and blood-based screening every 2 years, colonoscopy, computed tomography colonography, colon capsules, and sigmoidoscopy every 5 years, and colonoscopy at 45 years followed, if negative, by FIT every 2 years. Screening test and procedures performance were obtained from the literature. A microsimulation model reproducing the natural history of CRC was used to estimate the cost (€2018) and effectiveness [quality-adjusted life-years (QALYs)] of each strategy. A lifetime horizon was used. Costs and effectiveness were discounted at 3.5% annually. Results: Compared with no screening, colonoscopy and sigmoidoscopy at a 30% uptake were the most effective strategy (46.3 and 43.9 QALY/1000). FIT at a 30 µg/g threshold with 30% uptake was only half as effective (25.7 QALY). Colonoscopy was associated with a cost of €484,000 per 1000 individuals whereas sigmoidoscopy and FIT were associated with much lower costs (€123,610 and €66,860). Incremental cost-effectiveness rate for FIT and sigmoidoscopy were €2600/QALY ( versus no screening) and €3100/QALY ( versus FIT), respectively, whereas it was €150,000/QALY for colonoscopy ( versus sigmoidoscopy). With a lower threshold (10 µg/g) and a higher uptake of 45%, FIT was more effective and less costly than colonoscopy at a 30% uptake and was associated with an incremental cost–effectiveness ratio (ICER) of €4240/QALY versus no screening. Conclusion: At 30% uptake, current screening is the most effective screening strategy for high-risk individuals but is associated with a high ICER. Sigmoidoscopy and FIT at lower thresholds (10 µg/g) and a higher uptake should be given consideration as cost-effective alternatives. Plain Language Summary Cost-effectiveness analysis of colorectal cancer screening strategies in high-risk individuals Fecal occult blood testing with an immunochemical test (FIT) is generally considered as the most cost-effective alternative in colorectal cancer screening programs for average risk individuals without family history. Current screening guidelines for high-risk individuals with familial history recommend colonoscopy every 3–5 years. Colonoscopy every 3–5 years for individuals with familial history is the most effective strategy but is associated with a high incremental cost–effectiveness ratio. Compared with colonoscopy, if screening based on FIT is associated with a higher participation rate, it can achieve a similar effectiveness at a lower cost.

Background and aimAlthough recommended, the P-score used for assessing the pertinence / relevance of findings seen in small bowel (SB) capsule endoscopy (CE) is based on a low level of knowledge. The aim of this study was to evaluate the clinical relevance of the most frequent SBCE findings through an illustrated script questionnaire.Materials and MethodsSixteen types of SBCE findings were illustrated four times each in three different settings (occult and overt obscure gastrointestinal bleeding and suspected Crohn's disease), and with a variable number (n = 1/n = 2–5/n ≥ 6), thus providing a questionnaire with 192 scenarios and 576 illustrated questions. Fifteen international experts were asked to rate the finding's relevance for each question as very unlikely (−2) / unlikely (−1) / doubtful (0) / likely (+1) / very likely (+2). The median score (≤−0.75, between -0.75 and 0.75, or ≥0.75) obtained for each scenario determined a low (P0), intermediate (P1) or high (P2) relevance, respectively.Results8064 answers were analyzed. Participation and completion rates were 93% and 100%, respectively. In overt or occult OGIB, resultant P2 findings were 'typical angiectasia', 'deep ulceration', 'stenosis', and'blood', whatever their numbers, and 'superficial ulcerations' when multiple. While in suspected CD, consensus P2 lesions were 'deep ulceration' and 'stenosis' whatever their numbers, and 'aphthoid erosions' and 'superficial ulcerations' when multiple.ConclusionThis study establishes a guide for the evaluation of relevance of SBCE findings. It represents a step forward for SB-CE interpretation and is intended to be used as a tool for teaching and academic research.

Although duodenal adenomas and cancer appear to occur significantly less frequently in autosomal recessive MUTYH-associated polyposis (MAP) than in autosomal dominant familial adenomatous polyposis (FAP),1 current guidelines recommend similar endoscopic surveillance for both disorders.2-4 This involves gastro-duodenoscopy starting at 25 to 35 years of age and repeated at intervals determined by Spigelman staging based on the number, size, histological type and degree of dysplasia of adenomas, and by ampullary staging. Case reports of duodenal cancers in MAP suggest that they may develop in the absence of advanced Spigelman stage benign disease and even without coexisting adenomas.1 Recent molecular analyses suggest thatMAPduodenal adenomashave a higher mutational burden than FAP adenomas and are more likely to harbor oncogenic drivermutations, such as those in KRAS.5 These apparent differences in the biology and natural history of duodenal polyposis in FAP and MAP challenge the assumption that the same surveillance should be applied in both conditions.

Supplemental material, sj-docx-1-tag-10.1177_17562848211002359 for Cost-effectiveness analysis of alternative colorectal cancer screening strategies in high-risk individuals by Robert Benamouzig, Stéphanie Barré, Jean-Christophe Saurin, Henri Leleu, Alexandre Vimont, Sabrine Taleb and Frédéric De Bels in Therapeutic Advances in Gastroenterology

Background Cleanliness scores in small-bowel capsule endoscopy (SBCE) have poor reproducibility. The aim of this study was to evaluate a neural network-based algorithm for automated assessment of small-bowel cleanliness during capsule endoscopy. Methods 600 normal third-generation SBCE still frames were categorized as “adequate” or “inadequate” in terms of cleanliness by three expert readers, according to a 10-point scale, and served as a training database. Then, 156 third-generation SBCE recordings were categorized in a consensual manner as “adequate” or “inadequate” in terms of cleanliness; this testing database was split into two independent 78-video subsets for the tuning and evaluation of the algorithm, respectively. Results Using a threshold of 79 % “adequate” still frames per video to achieve the best performance, the algorithm yielded a sensitivity of 90.3 %, specificity of 83.3 %, and accuracy of 89.7 %. The reproducibility was perfect. The mean calculation time per video was 3 (standard deviation 1) minutes. Conclusion This neural network-based algorithm allowing automatic assessment of small-bowel cleanliness during capsule endoscopy was highly sensitive and paves the way for automated, standardized SBCE reports.

International audience; Many studies have focused on understanding the regulation and functions of aberrant protein synthesis in colorectal cancer (CRC), leaving the ribosome, its main effector, relatively underappreciated in CRC. The production of functional ribosomes is initiated in the nucleolus, requires coordinated ribosomal RNA (rRNA) processing and ribosomal protein (RP) assembly, and is frequently hyperactivated to support the needs in protein synthesis essential to withstand unremitting cancer cell growth. This elevated ribosome production in cancer cells includes a strong alteration of ribosome biogenesis homeostasis that represents one of the hallmarks of cancer cells. None of the ribosome production steps escape this cancer-specific dysregulation. This review summarizes the early and late steps of ribosome biogenesis dysregulations described in CRC cell lines, intestinal organoids, CRC stem cells and mouse models, and their possible clinical implications. We highlight how this cancer-related ribosome biogenesis, both at quantitative and qualitative levels, can lead to the synthesis of ribosomes favoring the translation of mRNAs encoding hyperproliferative and survival factors. We also discuss whether cancer-related ribosome biogenesis is a mere consequence of cancer progression or is a causal factor in CRC, and how altered ribosome biogenesis pathways can represent effective targets to kill CRC cells. The association between exacerbated CRC cell growth and alteration of specific steps of ribosome biogenesis is highlighted as a key driver of tumorigenesis, providing promising perspectives for the implementation of predictive biomarkers and the development of new therapeutic drugs.

International audience; MUTYH-associated polyposis (MUTYH-associated polyposis, MAP) is an autosomal recessive inheritance disorder related to bi-allelic constitutional pathogenic variants of the MUTYH gene which was first described in 2002. In 2011, a group of French experts composed of clinicians and biologists, performed a summary of the available data on this condition and drew up recommendations concerning the indications and the modalities of molecular analysis of the MUTYH gene in index cases and their relatives, as well as the management of affected individuals. In view of recent developments, some recommendations have become obsolete, in particular with regard to the molecular analysis strategy since MUTYH gene has been recently included in a consensus panel of 14 genes predisposing to colorectal cancer. This led us to revise all the points of the previous expertise. We report here the revised version of this work which successively considers the phenotype and the tumor risks associated with this genotype, the differential diagnoses, the indication criteria and the strategy of the molecular analysis and the recommendations for the management of affected individuals. We also discuss the phenotype and the tumor risks associated with mono-allelic pathogenic variants of MUTYH gene.

Main RecommendationsESGE recommends that individuals with Lynch syndrome should be followed in dedicated units that practice monitoring of compliance and endoscopic performance measures.Strong recommendation, low quality evidence, level of agreement 100 %.ESGE recommends starting colonoscopy surveillance at the age of 25 years for MLH1 and MSH2 mutation carriers and at the age of 35 years for MSH6 and PMS2 mutation carriers.Strong recommendation, moderate quality evidence, level of agreement 100 %. ESGE recommends the routine use of high-definition endoscopy systems in individuals with Lynch syndrome. Strong recommendation, high quality evidence, level of agreement 100 %. ESGE suggests the use of chromoendoscopy may be of benefit in individuals with Lynch syndrome undergoing colonoscopy; however routine use must be balanced against costs, training, and practical considerations.Weak recommendation, moderate quality evidence, level of agreement 89 %.ESGE recommends definition of familial risk of colorectal cancer as the presence of at least two first-degree relatives with colorectal cancer or at least one first-degree relative with colorectal cancer before the age of 50 years.Strong recommendation, moderate quality evidence, level of agreement 92 %.ESGE recommends colonoscopy surveillance in first-degree relatives of colorectal cancer patients in families that fulfill the definition of familial risk of colorectal cancer.Strong recommendation, moderate quality evidence, level of agreement 100 %.