Factors associated with early failure of peroral endoscopic myotomy in achalasia.

BACKGROUND AND AIMS: Achalasia can be treated very effectively with peroral endoscopic myotomy (POEM), but factors associated with early failure remain to be determined, especially in European cohorts. METHODS: All consecutive adult patients who underwent a first POEM to treat primary achalasia were included in this multicenter retrospective study. Early failure was defined by an Eckardt score (ES) >3 at 3 months after POEM. When evaluating factors predictive of early failure, 2 cohorts were considered: one consisted of the total population, for whom only basic variables were collected, and the other a cohort built for a case-control study that included matched early-failure and early-success patients (ratio, 1:2). RESULTS: Among 746 patients, the early failure rate was 9.4%. Predictive factors were age ≤45 years (P = .019), achalasia types I and III (P < .001), and the development of a severe adverse event during the procedure (P = .023). In the case-control study, the only additional independent risk factor for early failure was a high pre-POEM ES (P = .001). Only the retrosternal pain subscore was significantly associated with the early failure rate. CONCLUSION: The early failure rate of POEM used to treat primary achalasia is <10%. Younger age, type I/III achalasia, and a high pre-POEM ES were significantly associated with failure.

The risk of COVID-19 in IBD patients is increased by urban living and is not influenced by disease activity or intravenous biologics.

Background: Patients with inflammatory bowel disease (IBD) may have a modified immune response to SARS-CoV-2. The objectives were to evaluate the prevalence of COVID-19 in patients treated with infliximab or vedolizumab, to analyze the factors associated with the infection, the impact of treatments and trough levels. Methods: Patients with IBD treated with intravenous biologics in 14 French centers were included between March and June 2020 and followed-up for 6 months. Blood samples were collected for serologies and trough levels. The analysis of factors associated with COVID-19 was conducted in a matched 1:1 case-control sub-study with positive patients. Results: In total, 1026 patients were included (74.9% infliximab). Over the follow-up period, 420 patients reported the occurrence of COVID-19 symptoms; 342 had been tested of whom 18 were positive. At the end of follow-up, 38 patients had a positive serology. Considering both nasal tests and serologies together, 46 patients (4.5%) had been infected. The risk of COVID-19 was related neither to the use of treatments (whatever the trough levels) nor to disease activity. Infections were more frequent when using public transport or living in flats in urban areas. Conclusions: The prevalence rate of COVID-19 in this IBD population treated with intravenous infliximab or vedolizumab was the same as the one in the French population before the start of the vaccination campaign. The risk was increased by urban living and was not influenced by disease activity or biologics. Sanitary barrier measures remain the best way to protect against SARS-CoV-2 in patients with IBD in biological therapy.

Peroral endoscopic myotomy: is it better to perform it in naive patients or as second-line therapy? Results of an open-label-controlled study in 105 patients.

BACKGROUND: Whether Peroral Endoscopic Myotomy (POEM) can be proposed as a second-line treatment in patients with achalasia remains to be confirmed in real-life series. OBJECTIVE: This study aimed to compare the efficacy, feasibility and safety of POEM between treatment-naïve patients and patients who had prior endoscopic or surgical therapies for achalasia. METHODS: All consecutive patients who underwent a POEM procedure for achalasia in our centre from June 2015 to September 2018 were included in this retrospective study. They were classified into treatment-naïve patients (POEM1) and patients who had at least one previous endoscopic and/or surgical treatment for achalasia (POEM2). RESULTS: A total of 105 patients were included, 52 in the POEM1 group and 53 in the POEM2 group. Clinical success (defined as an Eckardt score ≤ 3) at 6 months was observed in 93% of POEM1 patients and 84% of POEM2 patients (p = 0.18). Technical success rate was not significantly different between the two groups (100% vs 96%, respectively; p = 0.50). No significant difference was noted in terms of adverse event rate (19% vs 19%, respectively; p = 1.00). Post-procedure pain occurred in 12% of treatment-naive and 9% of non-naïve patients (p = 0.76). The median length of hospital stay was 3 days in both groups (p = 0.17). Symptomatic gastroesophageal reflux occurred in 25% of POEM1 patients and 16% of POEM2 patients (p = 0.24). CONCLUSION: Efficacy, feasibility and safety of POEM are not different between treatment-naïve and non-naïve patients. POEM is a valuable second-line approach in patients with persistent symptoms of achalasia after surgical or endoscopic treatments.

Prognosis and chemosensitivity of non-colorectal alimentary tract cancers with microsatellite instability.

BACKGROUND: Data on outcomes of microsatellite instable and/or mismatch repair deficient (dMMR/MSI) digestive non-colorectal tumors are limited. AIMS: To evaluate overall survival (OS) of patients with dMMR/MSI digestive non-colorectal tumor. METHODS: All consecutive patients with a dMMR/MSI digestive non-colorectal tumor were included in this French retrospective multicenter study. RESULTS: One hundred and sixteen patients were included with a mean age of 63.6 years and 32.6% with a Lynch syndrome. Most tumors were oesophago-gastric (54.3%) or small bowel (32.8%) adenocarcinomas and at a localized stage at diagnosis (86.7%). In patients with localized tumors and R0 resection, median OS was 134.0 ± 64.2 months. Median disease-free survival (DFS) was 100.3 ± 65.7 months. Considering oesophago-gastric tumors, median DFS was improved when chemotherapy was added to surgery (not reached versus 22.8 ± 10.0 months, p = 0.03). In patients with advanced tumors treated by chemotherapy, median OS was 14.2 ± 1.9 months and median progression-free survival was 7.4 ± 1.6 months. CONCLUSION: dMMR/MSI digestive non-colorectal tumors are mostly diagnosed at a non-metastatic stage with a good prognosis. Advanced dMMR/MSI digestive non-colorectal tumors have a poor prognosis with standard chemotherapy.

Risk factors for clinical failure of peroral endoscopic myotomy in achalasia.

The recent development of per oral endoscopic myotomy (POEM) has been a game changer in the management of patients with achalasia. However, approximately 1 in 10 patients will not experience clinical success. The aim of this mini-review is to describe the current state of knowledge about the risk factors associated with POEM failure for the treatment of achalasia. Suspected risk factors are detailed into pre-, intra-, and post-procedural factors and put into perspective. Pre-procedural factors have been described, such as pre-treatment Eckardt score, previous treatments for achalasia, sigmoid type esophagus, significant esophageal dilatation, non-type II achalasia, young age and long duration of symptoms. An intra-procedural factor, mucosal injury during POEM, has also been associated with POEM failure. The occurrence of post-POEM GERD was identified as a controversial post-procedural factor associated with failure. The presumed mechanisms of POEM failure are incomplete myotomy or ineffective LES disruption, as confirmed by high-resolution manometry. However, when manometry confirms a significant decrease in LES pressure, it is likely that either impaired peristalsis or a morphologic abnormality such as extreme esophageal dilatation or severe tortuosity, which are not treated by POEM, should be suspected. Notably, a recently described adverse effect of POEM is the formation of a pseudo-diverticulum at the site of the myotomy (blown out myotomy). We finally stress the importance of performing a complete workup in case of POEM failure as different mechanisms of POEM failure should lead to different management.

Impact of antibiotic prophylaxis and conditioning modalities in per-oral endoscopic myotomy for esophageal motor disorders.

BACKGROUND AND AIMS: No recommendation regarding antibiotic prophylaxis and preparation modalities are available for patients with esophageal motor disorders who benefit from Per-Oral Endoscopic Myotomy (POEM). The aim of our study was to evaluate their impact on the POEM's safety. PATIENTS AND METHODS: This study was a comparative and multicentric retrospective analysis of a database prospectively collected. Patients over 18 years old with esophageal motor disorders confirmed by prior manometry, who underwent POEM were included. The primary endpoint was the occurrence of adverse events, as classified by Cotton, based on whether or not antibiotic prophylaxis was administered. RESULTS: A total of 226 patients (median age 52.9 ± 19.12 years [18-105], 116 women [51.3%]) were included. The indication for POEM was mainly type 2 achalasia (n = 135, 60.3%). Antibiotic prophylaxis was administered to 170 patients (75.2%) during 3.93 ± 3.46 days [1-21]. The overall adverse events rate was 9.3% (n = 21). Antibiotic prophylaxis was associated with the occurrence of adverse events (p = .003), but had no impact on their severity (p = .238). Antibiotic prophylaxis didn't influence the effectiveness of POEM (1 [0-4] vs 1 [0-9], p = .231). The use of a liquid diet in the 48 h prior to the procedure was significantly associated with a lower adverse events rate (3.1% vs 6.19%, p = .0002). CONCLUSION: The antibiotic prophylaxis during POEM does not prevent adverse events, had no impact on their severity and the efficacy of the procedure. A liquid diet before the procedure should be systematically proposed.

Altered epithelial barrier functions in the colon of patients with spina bifida.

Our objectives were to better characterize the colorectal function of patients with Spina Bifida (SB). Patients with SB and healthy volunteers (HVs) completed prospectively a standardized questionnaire, clinical evaluation, rectal barostat, colonoscopy with biopsies and faecal collection. The data from 36 adults with SB (age: 38.8 [34.1-47.2]) were compared with those of 16 HVs (age: 39.0 [31.0-46.5]). Compared to HVs, rectal compliance was lower in patients with SB (p = 0.01), whereas rectal tone was higher (p = 0.0015). Ex vivo paracellular permeability was increased in patients with SB (p = 0.0008) and inversely correlated with rectal compliance (r = - 0.563, p = 0.002). The expression of key tight junction proteins and inflammatory markers was comparable between SB and HVs, except for an increase in Claudin-1 immunoreactivity (p = 0.04) in SB compared to HVs. TGFß1 and GDNF mRNAs were expressed at higher levels in patients with SB (p = 0.02 and p = 0.008). The levels of acetate, propionate and butyrate in faecal samples were reduced (p = 0.04, p = 0.01, and p = 0.02, respectively). Our findings provide evidence that anorectal and epithelial functions are altered in patients with SB. The alterations in these key functions might represent new therapeutic targets, in particular using microbiota-derived approaches.Clinical Trials: NCT02440984 and NCT03054415.

Serum Pepsinogens Combined with New Biomarkers Testing Using Chemiluminescent Enzyme Immunoassay for Non-Invasive Diagnosis of Atrophic Gastritis: A Prospective, Multicenter Study.

BACKGROUND: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), a gastric precancerous lesion, is of growing interest for identification of patients at increased risk of gastric cancer. The aim was to analyze the diagnostic performance of serum pepsinogen testing using another method, chemiluminescent enzyme immunoassay (CLEIA), as well as of other new potential biomarkers. MATERIAL AND METHODS: The sera of patients considered at increased risk of gastric cancer and undergoing upper endoscopy collected in our previous prospective, multicenter study were tested for pepsinogen I (PGI) and II (PGII), interleukin-6 (IL-6), human epididymal protein 4 (HE-4), adiponectin, ferritin and Krebs von den Lungen (KL-6) using the CLEIA. The diagnostic performance for the detection of AG was calculated by taking histology as the reference. RESULTS: In total, 356 patients (162 men (46%); mean age 58.6 (±14.2) years), including 152 with AG, were included. For the detection of moderate to severe corpus AG, sensitivity and specificity of the pepsinogen I/II ratio were of 75.0% (95%CI 57.8-87.9) and 92.6% (88.2-95.8), respectively. For the detection of moderate to severe antrum AG, sensitivity of IL-6 was of 72.2% (95%CI 46.5-90.3). Combination of pepsinogen I/II ratio or HE-4 showed a sensitivity of 85.2% (95%CI 72.9-93.4) for the detection of moderate to severe AG at any location. CONCLUSION: This study shows that PG testing by CLEIA represents an accurate assay for the detection of corpus AG. Additionally, IL-6 and HE-4 may be of interest for the detection of antrum AG. MINI-ABSTRACT: Pepsinogens testing by chemiluminescent enzyme immunoassay is accurate for the detection of corpus atrophic gastritis. IL-6 and HE-4 maybe of interest for the detection of antrum atrophic gastritis.

Endoscopy to Diagnose and Prevent Digestive Cancers in Lynch Syndrome.

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.

Full-field optical coherence tomography: novel imaging technique for extemporaneous high-resolution analysis of mucosal architecture in human gut biopsies.

Full-field optical coherence tomography (FFOCT) is an imaging technique of biological tissue based on tissue light reflectance analysis. We evaluated the feasibility of imaging fresh digestive mucosal biopsies after a quick mounting procedure (5 min) using two distinct modalities of FFOCT. In static FFOCT mode, we gained high-resolution images of general gut tissue-specific architecture, such as oesophageal papillae, gastric pits, duodenal villi and colonic crypts. In dynamic FFOCT mode, we imaged individual epithelial cells of the mucosal lining with a cellular or subcellular resolution and identified cellular components of the lamina propria. FFOCT represents a promising dye-free imaging tool for on-site analysis of gut tissue remodelling.

A panel of stomach-specific biomarkers (GastroPanel®) for the diagnosis of atrophic gastritis: A prospective, multicenter study in a low gastric cancer incidence area.

BACKGROUND: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence. MATERIAL AND METHODS: In this prospective, multicenter, cross-sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin-17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference. RESULTS: Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P = .015] and corpus AG [61.0% (95% CI 49.2; 72.0), P = .004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P = .068). CONCLUSION: Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.

First Detection in Helicobacter suis of a Mutation Conferring Resistance to Clarithromycin in Helicobacter pylori: Case Report and Review of the Literature.

Helicobacter pylori and non-H. pylori Helicobacter (NHPH) are associated with gastritis, ulcer, and gastric neoplasia. Because of the impossibility to culture them, diagnosis remains based on microscopic examination and molecular analysis of biopsies. Owing to the lack of data concerning antibiotic resistance of NHPH, infected patients are usually treated using antibiotics, including clarithromycin. Herein, we describe, for the first time a human infection by Helicobacter suis harboring a mutation associated to clarithromycin resistance in H. pylori. Eradication was successful with a metronidazole-based treatment. This observation highlights the benefit to use genotypic detection of resistance to improve therapeutic management of NHPH infections.

Defecation disorders in Spina Bifida: Realistic goals and best therapeutic approaches.

AIMS: Spina Bifida (SB) is a rare congenital condition that frequently impairs the neurological control of both fecal continence and defecation. Several therapeutic strategies have been proposed but impact assessment is lacking. Our objectives were to quantify the symptomatic improvement and to determine the optimal strategy in this rare condition where randomized controlled trials are difficult to conduct. METHODS: Data were extracted from a prospective database. The present analysis focused on patients having undergone at least two gastroenterological assessments. A standardized therapeutic approach was used from the first visit. Improvement was quantified by the variation of quantified symptomatic scores. RESULTS: The data of of 57 adults with SB (gender F/M: 30/27 [52.6/47.4%]; mean age: 33.8 [18.5] years) were extracted. After a mean follow-up of 46 months, 23/57 patients (40.4%) had at least improvement of one point of the Cleveland Clinic Incontinence score (CCIS); 13/57 (22.8%) reported a significant improvement of continence (delta score >50%). Five of the twelve patients (41.6%) with CCIS < 5 at baseline became incontinent over time. The neurological level was not associated with a worse continence outcome. Work on stool consistency and transanal irrigation were the most useful strategies in those with significant improvement of continence. CONCLUSIONS: Using conventional strategies, a benefit on fecal continence occurs in only one out of five patients suffering from Spina Bifida and continent patients at baseline can develop fecal incontinence over time. A strategy targeting improved control of defecation (transanal irrigation) and a standardization of follow-up protocol might be beneficial.