Case Series of 11 CDH1 Families (47 Carriers) Including Incidental Findings, Signet Ring Cell Colon Cancer and Review of the Literature.

Germline pathogenic variants in E-cadherin (CDH1) confer high risk of developing lobular breast cancer and diffuse gastric cancer (DGC). The cumulative risk of DGC in CDH1 carriers has been recently reassessed (from 40-83% by age 80 to 25-42%) and varies according to the presence and number of gastric cancers in the family. As there is no accurate estimate of the risk of gastric cancer in families without DGC, the International Gastric Cancer Linkage Consortium recommendation is not straightforward: prophylactic gastrectomy or endoscopic surveillance should be proposed for these families. The inclusion of CDH1 in constitutional gene panels for hereditary breast and ovarian cancer and for gastrointestinal cancers, recommended by the French Genetic and Cancer Consortium in 2018 and 2020, leads to the identification of families with lobular cancer without DGC but also to incidental findings of pathogenic variants. Management of CDH1 carriers in case of incidental findings is complex and causes dilemmas for both patients and providers. We report eleven families (47 CDH1 carriers) from our oncogenetic department specialized in breast and ovarian cancer, including four incidental findings. We confirmed that six families did not have diffuse gastric cancer in their medical records. We discuss the management of the risk of diffuse gastric cancer in Hereditary Lobular Breast Cancer (HLBC) through a family of 11 CDH1 carriers where foci were identified in endoscopic surveillance. We also report a new colon signet ring cancer case in a CDH1 carrier, a rare aggressive cancer included in CDH1-related malignancies.

Lactobacillus gasseri LA806 Supplementation in Patients with Irritable Bowel Syndrome: A Multicenter Study.

The potential benefits of Lactobacillus gasseri LA806 in IBS were previously identified in a comprehensive preclinical research program. The purpose of this multicenter study was to explore in real-life conditions changes in IBS symptoms and quality of life in patients receiving a 4-week supplementation with L. gasseri LA806. Altogether 119 patients meeting Rome IV criteria for IBS were included, of whom 118 received the supplement. The majority of patients (71.8% (95% CI 63.6−79.9%)) manifested a ≥30% decrease in abdominal pain at 4 weeks, the mean abdominal pain score diminishing by 54.2% (from 5.3 ± 2.2 to 2.2 ± 2.4, p < 0.0001). A statistically significant decrease in abdominal pain was seen as early as the first week. A decrease of ≥30% in both abdominal pain score and global IBS symptom score was attained in 61.5% of patients (95% CI 51.7−71.2%). The mean IBS-SSS score fell by 152 ± 112 points (p = 0.001), with symptoms being attenuated in 85% of patients (CGI-I). Supplementation led to a 10-fold decrease in the number of patients reporting severe IBS symptoms. The concomitant intake of antidiarrheals, antispasmodics and analgesics decreased and quality of life scores significantly improved. These preliminary results warrant confirmation by a randomized, placebo-controlled study that this study will allow a better design.

Prokaryotic and Eukaryotic Fecal Microbiota in Irritable Bowel Syndrome Patients and Healthy Individuals Colonized With Blastocystis.

Blastocystis is the most frequently isolated protozoan from human stool. Its role in human health is still debated, and a high prevalence was reported in irritable bowel syndrome (IBS) subjects, suggesting a potential link with microbiota. In the present study, we aimed to investigate prokaryotic and eukaryotic microbiota in both IBS-C (constipated) and healthy individuals. We recruited 35 IBS-C patients and 23 healthy subjects, from which 12 and 11 carried Blastocystis, respectively. We performed 16S and 18S rRNA high-throughput sequencing on feces. Whereas we did not observe differences between infected and non-infected controls, several phyla were significantly modified in IBS-C patients according to the presence of Blastocystis. Tenericutes phylum and Ruminococcaceae family were especially increased in Blastocystis carriers. Furthermore, colonization with Blastocystis was associated with discrete changes in the microbial eukaryome, particularly among the Fungi taxa. Depending on the group of patients considered, the mycobiota changes do not go in the same direction and seem more deleterious in the IBS-C group. These results encourage further in vivo and in vitro investigations concerning the role of Blastocystis in the gut environment.

The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.

BACKGROUND: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe. METHODS: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT. FINDINGS: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres. INTERPRETATION: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need. FUNDING: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).

[Intestinal microbiota and allogeneic stem cell transplantation]. / Microbiote intestinal et allogreffe de cellules souches hématopoïétiques.

Allogeneic hematopoïetic stem cell transplantation is one of the most efficient curative treatment for acute leukemia. But it is also a heavy process with an important risk of complications, particularly infection and graft versus host disease. Increasing data in literature show that an alteration of the intestinal microbiota of allogeneic stem cell recipients is associated with these complications. Indeed, treatments used during conditioning regimen lead to an impaired microbiota, which cannot fulfill its protective functions anymore. To limit this microbiota impairment, we could restore a healthy microbiota by a fecal microbiota transplantation, which has already shown its efficiency in the treatment of Clostridium difficile infection. The aim of this review is to describe the intestinal microbiota, the link between microbiota and complications of allogeneic stem cells transplantation, and the recent published data on fecal microbiota transplantation in this field.

Assessment of the effectiveness and safety of ethosuximide in the treatment of abdominal pain related to irritable bowel syndrome - IBSET: protocol of a randomised, parallel, controlled, double-blind and multicentre trial.

INTRODUCTION: Irritable bowel syndrome (IBS) is characterised by the association of abdominal chronic pain with bowel habit disorders in the absence of identifiable organic disease. This is the first reason for consultation in gastroenterology, with an estimated prevalence of 10%-15% in industrialised countries. Although this is a benign gastrointestinal disease, its chronicity profoundly impacts the patient's quality of life and causes considerable health spending. Actual medical treatments are poorly efficient on IBS-related abdominal pain, making it a major public health concern. The mechanisms causing IBS symptoms are unknown. Recent studies have shown the involvement of T-type channel in abdominal pain. We aim to evaluate the therapeutic potential of ethosuximide, a T-type channel blocker, on the abdominal pain of patients presenting an IBS. METHODS AND ANALYSIS: The IBSET trial is a randomised, controlled, parallel, double-blind and multicentre study. It is the first clinical trial evaluating the efficacy and safety of ethosuximide on abdominal pain related to IBS. Adults with IBS that report significant abdominal pain (≥4/10) at least for 3 months will be included. 290 patients will be randomly assigned to receive either ethosuximide or placebo over 12 weeks after 1 week of run-in period. The primary endpoint is the rate of responders (pain reduction ≥30% and Subject Global Assessment of Relief score ≥4). The intensity of abdominal pain will be assessed by an 11-point Numerical Rating Scale before and after 12 weeks of treatment and the score of the Subject Global Assessment of Relief scale at the end of treatment. The secondary endpoints are the safety of ethosuximide, the intensity and features of IBS and quality of life. ETHICS AND DISSEMINATION: The study was approved by an independent medical ethics committee (CPP Sud-Est VI, Clermont-Ferrand, France). The results will be published in a peer-review journal and presented at international congresses. TRIAL REGISTRATION NUMBER: NCT02973542; Pre-results.

Adenoma detection with blue-water infusion colonoscopy: a randomized trial.

Background and aims Colonoscopy is currently the reference method to detect colorectal neoplasia, yet some adenomas remain undetected. The water infusion technique and dying with indigo carmine has shown interesting results for reducing this miss rate. The aim of this study was to compare the adenoma detection rate (adenoma and adenocarcinoma; ADR) and the mean number of adenomas per patient (MAP) for blue-water infusion colonoscopy (BWIC) versus standard colonoscopy. Methods We performed a multicenter, randomized controlled trial in eight units, including patients with a validated indication for colonoscopy (symptoms, familial or personal history, fecal occult blood test positive). Consenting patients were randomized 1:1 to BWIC or standard colonoscopy. All colonoscopies were performed by experienced colonoscopists. All colonoscopy quality indicators were prospectively recorded. Results Among the 1065 patients included, colonoscopies were performed completely for 983 patients (514 men; mean age 59.1). The ADR was not significantly different between the groups; 40.4 % in the BWIC group versus 37.5 % in the standard colonoscopy group (odds ratio [OR] 1.13; 95 % confidence interval [CI] 0.87 - 1.48; P = 0.35). MAP was significantly greater in the BWIC group (0.79) than in the standard colonoscopy group (0.64; P = 0.005). For advanced adenomas, the results were 50 (10.2 %) and 36 (7.3 %), respectively (P = 0.10). The cecal intubation rate was not different but the time to cecal intubation was significantly longer in BWIC group (9.9 versus 6.2 minutes; P < 0.001). Conclusion Despite the higher MAP with BWIC, the routine use of BWIC does not translate to a higher ADR. Whether increased detection ultimately results in a lower rate of interval carcinoma is not yet known. CLINICAL TRIALS REGISTRATION: EudraCT 2012-A00548 - 35; NCT01937429.

Temporary placement of a covered duodenal stent can avoid riskier anterograde biliary drainage when ERCP for obstructive jaundice fails due to duodenal invasion.

BACKGROUND: Duodenal stenosis is one of the most common causes of failed ERCP for obstructive jaundice. Alternative approaches include anterograde biliary drainage, with higher morbidity. We report in this study the efficacy and safety of temporary placement of a covered duodenal self-expandable metal stent (cSEMS) in order to access the papilla and achieve secondary retrograde biliary drainage in patients with obstructive jaundice and failed ERCP due to concomitant duodenal stenosis. METHODS: From June 2006 to March 2014, a total of 26 consecutive patients presenting obstructive jaundice without severe sepsis with failed ERCP due to duodenal invasion were enrolled. A temporary 7-day duodenal cSEMS was placed during the failed ERCP, and a second ERCP was attempted at day 7 after duodenal stent removal. RESULTS: Duodenal cSEMS placement and retrieval were technically successful in all cases. Access to the papilla at day 7 was possible in 25 cases (96 %, 95 % CI 80-99 %). Secondary successful ERCP was achieved in 19 cases (76 %, 95 % CI 55-91 %, i.e., 73 %, 95 % CI 73-86 %, in an intention-to-treat analysis). Mean bilirubin level was 102 ± 90 µmol/L at baseline rising to 164 ± 121 µmol/L at day 7. There were 6 stent migrations and no adverse events recorded between the two ERCPs. CONCLUSIONS: When ERCP for obstructive jaundice fails due to duodenal invasion, temporary cSEMS placement offers a safe and effective way to achieve successful secondary ERCP while avoiding riskier endoscopic ultrasound or percutaneous transhepatic anterograde biliary drainage.

Faecal microbiota transplantation in recurrent Clostridium difficile infection: Recommendations from the French Group of Faecal microbiota Transplantation.

Faecal microbiota transplantation is effective for treating recurrent forms of Clostridium difficile infection and its use in this indication is recommended in the most recent European and North American guidelines. In this context, faecal microbiota transplantation is beginning to be performed in France in clinical practice, while the rules governing this procedure have been defined in France only for clinical trials. To unify, secure, and evaluate practice in this field in France, the French Group of Faecal microbiota Transplantation (FGFT) was created in October 2014 with the support of the French National Society of Gastroenterology, the French Infectious Disease Society, and the National Academy of Pharmacy. We present here the deliberations of this group regarding the use of faecal microbiota transplantation for recurrent Clostridium difficile infection. The issues addressed are the indications, therapeutic sequence, delivery procedures, donor selection, methods and conditions of specimen preparation, and traceability.

Diffusion-weighted magnetic resonance enterocolonography in predicting remission after anti-TNF induction therapy in Crohn's disease.

BACKGROUND: Diffusion-weighted magnetic resonance entero-colonography (DW-MREC) with no rectal distension and with no bowel cleansing is accurate to assess inflammatory activity in ileocolonic Crohn's disease (CD). AIM: To study DW-MREC parameters as predictors of remission (CDAI < 150 and CRP < 5mg/L) after anti-TNF induction therapy. METHODS: Forty consecutive CD patients were prospectively and consecutively included. All the patients underwent DW-MREC with apparent diffusion coefficient (ADC) and MaRIA calculation before starting anti-TNF. Mean ADC was defined as the mean of the segmental ADC. RESULTS: Twenty patients (50.0%) experienced remission at W12. Low mean ADC (2.05 ± 0.22 vs 1.89 ± 0.25, p = 0.03) and high total MaRIA (39.2 ± 16.6 vs 51.7 ± 18.2, p = 0.03) were predictive of remission at W12. Using a ROC curve, we determined a mean ADC of 1.96 as predictive cut-off of remission at W12 (AUC = 0.703 [0.535-0.872]) with sensitivity, specificity, positive predictive value and negative predictive value of 70.0%, 65.0%, 66.7% and 68.4%, respectively. In multivariate analysis, mean ADC < 1.96 (OR = 4.87, 95% CI [1.04-22.64]) and total MaRIA > 42.5 (OR = 5.11, 95% CI [1.03-25.37]), reflecting high inflammatory activity, were predictive of remission at week 12. CONCLUSIONS: DW-MREC using quantitative parameters i.e. ADC, is useful in detecting and assessing inflammatory activity but also to predict efficacy of anti-TNF induction therapy in CD.

Blastocystis is associated with decrease of fecal microbiota protective bacteria: comparative analysis between patients with irritable bowel syndrome and control subjects.

Blastocystis is a protistan parasite living in the digestive tract of many animals, including humans. This highly prevalent intestinal parasite is suspected to be linked to Irritable Bowel Syndrome (IBS), a chronic functional bowel disorder. Here, we first compared the prevalence of Blastocystis among 56 IBS patients (40 IBS with constipation (IBS-C), 9 IBS with diarrhea (IBS-D), 4 mixed IBS (IBS-M) and 3 unsubtyped IBS (IBS-U) according to the Rome III criteria) and 56 control (i.e. without any diagnosed chronic or acute gastrointestinal disorder) subjects. The highest prevalence of Blastocystis spp. was observed in the IBS group, but was only statistically significant in men (36.8% in the IBS group versus 4.8% in the control group). We then conducted a meta-analysis including epidemiological studies attempting to determine whether Blastocystis carriage could be linked to IBS, and highlighted that IBS patients had a relative risk of 2.34 to be infected by Blastocystis when compared to non-IBS subjects. We also looked for Dientamoeba fragilis, which is often associated with IBS, and identified this parasite only in some IBS patients (n = 6/56). Several studies provided evidence for a major role of the gut microbiota in the pathophysiology of IBS. Thus, we investigated the possible impact of Blastocystis carriage on the enteric bacterial community through quantification of 8 major bacterial groups from the enteric flora. Our data indicated that men with IBS-C had a significant decrease in Bifidobacterium sp. when infected by Blastocystis. Interestingly, in control subjects (i.e. without any gastrointestinal disorder) positive for Blastocystis, Faecalibacterium prausnitzii, which is known for its anti-inflammatory properties, was significantly decreased in men. Our results support the hypothesis that Blastocystis might be linked to the pathophysiology of IBS-C and intestinal flora imbalance.

Pancreatic intubation facilitated by methylene blue injection decreases the risk for postpapillectomy acute pancreatitis.

OBJECTIVES: Endoscopic snare papillectomy (ESP) is a viable alternative to surgical treatment of ampullary adenomas and T1N0 stage ampullary carcinomas. The main drawback of this technique is the high risk of acute pancreatitis post procedure.The aim of this study was to assess the efficacy, safety, and long-term results of this procedure, and to determine whether routine pancreatic intubation facilitated by intraductal methylene blue (MB) injection reduces the risk for pancreatitis. PATIENTS AND METHODS: Between 2004 and 2011, 56 consecutive patients underwent ESP. Before resection, the pancreatic duct was cannulated, and MB was injected intraductally to facilitate stent placement after ampullectomy. RESULTS: ESP was performed en bloc in 45 patients with histological findings of low-grade dysplasia (39%), high-grade dysplasia (25%), carcinoma (32.5%), and others (3.5%). The morbidity rate was 19.5%: acute pancreatitis (n=6), bleeding (n=4), perforation (n=1), and sepsis (n=1). Pancreatic intubation was performed in 89% of the patients. Postprocedure pancreatitis occurred significantly less in the patients with a pancreatic stent than in those without: 3/49 versus 3/6, P=0.013. ESP was considered as curative in 39 patients (75%). Of the 12 recurrences (25%), 10 were managed endoscopically, but with higher morbidity (acute pancreatitis=40%). CONCLUSION: Endoscopic papillectomy is safe and effective in the hands of experts. Pancreatic-duct stent placement in fewer cannulation attempts could be facilitated by injection of MB before papillectomy, and this decreases the risk for postprocedure pancreatitis. Recurrences can be managed endoscopically, but with a higher risk for pancreatitis.