Systematic Resection of the Visible Scar After Incomplete Endoscopic Resection of Rectal Neuroendocrine Tumors.

INTRODUCTION: When initial resection of rectal neuroendocrine tumors (r-NETs) is not R0, persistence of local residue could lead to disease recurrence. This study aimed to evaluate the interest of systematic resection of non-R0 r-NET scars. METHODS: Retrospective analysis of all the consecutive endoscopic revisions and resections of the scar after non-R0 resections of r-NETs. RESULTS: A total of 100 patients were included. Salvage endoscopic procedure using endoscopic submucosal dissection or endoscopic full-thickness resection showed an R0 rate of near 100%. Residual r-NET was found in 43% of cases. DISCUSSION: In case of non-R0 resected r-NET, systematic scar resection by endoscopic full-thickness resection or endoscopic submucosal dissection seems necessary.

The PRSS3P2 and TRY7 deletion copy number variant modifies risk for chronic pancreatitis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Endoscopic resection of early esophageal tumors in patients with cirrhosis or portal hypertension: a multicenter observational study.

BACKGROUND: Liver cirrhosis and esophageal cancer share several risk factors, such as alcohol intake and excess weight. Endoscopic resection is the gold standard treatment for superficial tumors. Portal hypertension and coagulopathy may increase the bleeding risk in these patients. This study aimed to assess the safety and efficacy of endoscopic resection for early esophageal neoplasia in patients with cirrhosis or portal hypertension. METHODS: This retrospective multicenter international study included consecutive patients with cirrhosis or portal hypertension who underwent endoscopic resection in the esophagus from January 2005 to March 2021. RESULTS: 134 lesions in 112 patients were treated, including by endoscopic submucosal dissection in 101 cases (75 %). Most lesions (128/134, 96 %) were in patients with liver cirrhosis, with esophageal varices in 71 procedures. To prevent bleeding, 7 patients received a transjugular intrahepatic portosystemic shunt, 8 underwent endoscopic band ligation (EBL) before resection, 15 received vasoactive drugs, 8 received platelet transfusion, and 9 underwent EBL during the resection procedure. Rates of complete macroscopic resection, en bloc resection, and curative resection were 92 %, 86 %, and 63 %, respectively. Adverse events included 3 perforations, 8 delayed bleedings, 8 sepsis, 6 cirrhosis decompensations within 30 days, and 22 esophageal strictures; none required surgery. In univariate analysis, cap-assisted endoscopic mucosal resection was associated with delayed bleeding (P = 0.01). CONCLUSIONS: In patients with liver cirrhosis or portal hypertension, endoscopic resection of early esophageal neoplasia appeared to be effective and should be considered in expert centers with choice of resection technique, following European Society of Gastrointestinal Endoscopy guidelines to avoid undertreatment.

Use of endoscopic submucosal dissection or full-thickness resection device to treat residual colorectal neoplasia after endoscopic resection: a multicenter historical cohort study.

INTRODUCTION : Residual colorectal neoplasia (RCN) after previous endoscopic mucosal resection is a frequent challenge. Different management techniques are feasible including endoscopic full-thickness resection using the full-thickness resection device (FTRD) system and endoscopic submucosal dissection (ESD). We aimed to compare the efficacy and safety of these two techniques for the treatment of such lesions. METHODS : All consecutive patients with RCN treated either using the FTRD or by ESD were retrospectively included in this multicenter study. The primary outcome was the R0 resection rate, defined as an en bloc resection with histologically tumor-free lateral and deep margins. RESULTS : 275 patients (median age 70 years; 160 men) who underwent 177 ESD and 98 FTRD procedures for RCN were included. R0 resection was achieved in 83.3 % and 77.6 % for ESD and FTRD, respectively (P = 0.25). Lesions treated by ESD were however larger than those treated by FTRD (P < 0.001). The R0 rates for lesions of 20-30 mm were 83.9 % and 57.1 % in the ESD and FTRD groups, respectively, and for lesions of 30-40 mm were 93.6 % and 33.3 %, respectively. On multivariable analysis, ESD procedures were associated with statistically higher en bloc and R0 resection rates after adjustment for lesion size (P = 0.02 and P < 0.001, respectively). The adverse event rate was higher in the ESD group (16.3 % vs. 5.1 %), mostly owing to intraoperative perforations. CONCLUSION: ESD is effective in achieving R0 resection for RCN whatever the size and location of the lesions. When residual lesions are smaller than 20 mm, the FTRD is an effective alternative.

Compliance with follow-up guidelines after high-risk colorectal polyp removal: a population-based study.

BACKGROUND AND AIMS: After high-risk colorectal adenoma removal, colorectal cancer risk remains higher than that in the general population. Depending on polyp characteristics, a 3-month or 3-year follow-up colonoscopy is recommended, and clear follow-up instructions must be given to the patient. Our primary aim was to evaluate compliance with French follow-up recommendations. Second, we evaluated the impact of how the information was given and if patients actually underwent their control colonoscopy according to the instructions given. METHODS: We collected data from the Burgundy polyp population-based registry and medical records from the endoscopy centers of the area. Between June 30, 2014 and July 1, 2015, 405 patients were included in this study. RESULTS: Written follow-up instructions were provided to 345 patients (85.2%), and 184 of them (53.3%) complied with guidelines. For 29.9% the interval to follow-up colonoscopy was longer than recommended, and for 6.4% the interval was shorter. Among the 303 patients who had clear follow-up instructions, 42.2% had their control colonoscopy and 83.6% respected the stipulated interval. Follow-up instructions were found in the colonoscopy report in at least 49% of cases. CONCLUSIONS: Compliance with follow-up guidelines was poor: Inappropriate intervals were often longer than recommended. Patients with written follow-up instructions and those who underwent follow-up colonoscopy mostly followed these instructions. Ensuring compliance with guidelines and giving written instructions to patients should be primary goals to achieve effective follow-up. Gastroenterologist training should be improved in this way.

Continuous Anti-TNFα Use Throughout Pregnancy: Possible Complications For the Mother But Not for the Fetus. A Retrospective Cohort on the French National Health Insurance Database (EVASION).

OBJECTIVES: Inflammatory bowel diseases (IBD) need long-term treatment, which can influence pregnancies in young women. Uncontrolled IBD is associated with poor pregnancy outcomes. Despite the labeling of Anti-tumor necrosis factor (TNF) antibodies (anti-TNFα) which indicates that their use is not recommended during pregnancy, anti-TNFα are increasingly being used during pregnancy and may expose women and their fetuses to treatment-related complications. Existing recommendations on the timing of treatment during pregnancy are inconsistent. We aimed to assess the safety of anti-TNFα treatment in pregnant women with IBD, and up to the first year of life for their children. METHODS: An exposed/non exposed retrospective cohort was conducted on the French national health system database SNIIRAM (Système National d'Information Inter-Régimes de l'Assurance Maladie). All IBD women who became pregnant between 2011 and 2014 were included. Women with concomitant diseases potentially treated with anti-TNFα were excluded. Anti-TNFα exposure (infliximab, adalimumab, golimumab or certolizumab pegol) during pregnancy was retrieved from the exhaustive prescription database in SNIIRAM. The main judgment criterion was a composite outcome of disease-, treatment- and pregnancy-related complications during pregnancy for the mother, and infections during the first year of life for children. RESULTS: We analyzed data from 11,275 pregnancies (8726 women with IBD), among which 1457 (12.9%) pregnancies were exposed to anti-TNFα, mainly infliximab or adalimumab, with 1313/7722 (17.0%) suffering from Crohn's disease and 144/3553 (4.1%) from ulcerative colitis. After adjusting for disease severity, steroid use, age, IBD type, and duration and concomitant 6-mercaptopurine use, anti-TNFα treatment was associated with a higher risk of overall maternal complications (adjusted Odds Ratio (aOR) = 1.49; 95% confidence interval (CI): 1.31-1.67) and infections (aOR = 1.31; 95% CI: 1.16-1.47). Maintaining anti-TNFα after 24 weeks did not increase the risk of maternal complication, but interrupting the anti-TNFα increased relapse risk. No increased risk for infection was found in children (aOR = 0.89; 95% CI: 0.76-1.05) born to mother exposed to anti-TNFα during pregnancy. CONCLUSIONS: Anti-TNFα treatment during pregnancy increased the risk of maternal complications compared to unexposed; however, discontinuation before week 24 increased the risk of disease flare. There was no increased risk for children exposed to anti-TNFα up to 1 year of life.

A French national survey on the use of antibiotic prophylaxis in cirrhotic patients.

BACKGROUND: Guidelines recommend antibiotic prophylaxis (AP) in well-selected groups of cirrhotic patients, but the impact of these recommendations has not been assessed in France. AIM: To evaluate AP prescription tendencies for gastrointestinal bleeding, and primary and secondary prophylaxis of spontaneous bacterial peritonitis (SBP). METHODS: Practitioners (n = 1,159) working in general hospitals (GH) or in university hospitals (UH) received a self-administered questionnaire. RESULTS: Three hundred and eighty-nine (33.6%; GH 35% and UH 30.4%) practitioners responded. AP was prescribed by 97.7%, 72.3% and 94.8% of practitioners, without significant differences between UH and GH, respectively, for gastrointestinal bleeding (quinolones 48.2%, third-generation cephalosporins 27.7% and amoxicillin-clavulanic acid 22.2%), primary (quinolones 97.2%) and secondary prophylaxis of SBP (quinolones 99%). For gastrointestinal bleeding, ofloxacin (47.6%) and norfloxacin (37.4%) were the main quinolones prescribed, and ceftriaxone (77%) was the main third-generation cephalosporin prescribed. The principal reasons for prescribing AP were a decrease in bacterial infection (88.9% for gastrointestinal bleeding, 91.3% for primary and 94.3% for secondary prophylaxis of SBP), a recommendation by a consensus conference (83%, 38% and 74.4% respectively) and an improvement in survival (72.8%, 41.3% and 57.7% respectively). Only 31.7% of practitioners (39.6% for UH vs. 28.6% for GH; P = 0.038) believed that AP may reduce the risk of bleeding recurrence. Reported side effects (28%) of AP mainly concerned the risk of quinolone resistance (62% of cases). CONCLUSION: Antibiotic prophylaxis is well-recognized by French practitioners, but its routine use depends on the expertise of practitioners. Quinolones remain the main antibiotic class prescribed irrespective of the type of prophylaxis.

High serum levels of free cortisol indicate severity of cirrhosis in hemodynamically stable patients.

BACKGROUND AND AIM: We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T(30)) the low-dose 1-µg short synacthen test (LD-SST); and (ii) the prognostic value of SFC and STC. METHODS: Consecutive, hemodynamically stable, cirrhotic patients (34 Child-Pugh class A, 29B, and 32C) underwent the LD-SST. Patients were followed for at least 12 months to assess non-transplant-related mortality. RESULTS: Child-Pugh class C patients had significantly higher basal levels of SFC than Child-Pugh class A or B patients. Prevalence of suspected adrenal dysfunction ranged between 7.4% (T(0) STC < 138 nmol/L) and 49.4% (change in STC < 250 nmol/L) according to the threshold used. In receiver-operator curve analysis, the area-under-the-curve values were 0.67 for T(30) SFC (0.51-0.79), 0.81 for Child-Pugh score (0.70-0.88), and 0.79 for albumin level (0.63-0.88). During the follow-up period, 16 patients with high T(30) SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T(30) SFC (< 78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T(30) SFC, log-rank test). Albeit not statistically significant, the risk of death for patients with T(30) SFC ≥ 78.9 nmol/L was fivefold higher than for patients with lower levels after adjusting for cirrhosis severity and level of albumin. CONCLUSIONS: One-year, non-transplant-related mortality is high among patients with T(30) levels of SFC ≥ 78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress in hemodynamically stable cirrhotic patients, detected by adrenal testing.

A colonoscopy quality improvement intervention in an endoscopy unit.

Many studies identified colonoscopy quality indicators in order to improve performance and safety. We conducted a colonoscopy improvement study. Our study was designed according to a Plan-Do-Study-Act cycle: first recording of our quality indicators and identification of shortcomings, second identification of improvement targets and implementation of new procedures, third second recording of quality indicators, fourth validation of procedures and identification of new goals. Quality indicators derived from European and French guidelines were recorded before and after our improvement actions. We were mainly interested in the quality indicators of the colonic preparation, the description of the diagnosed lesions and on the examination reports. The data of 134 patients prospectively included in January-February 2017 were compared to 133 patients included in May-June 2019, after implementation of improvement procedures, in the digestive endoscopy unit of the university hospital of Dijon, France. Our intervention, and in particular the implementation of new standardized forms, improved preparation quality: Boston Bowel Preparation Scale scores increased significantly from 7.8 to 8.2. Cecal intubation rate increased by 6%, and more adenomas were diagnosed and removed (+3.3%). Adenoma detection rate increased significantly from 26 to 42%. The completion of withdrawal time measure improved from 6.7 to 100%. Our study led to the rapid implementation of corrective actions and improved quality in our unit and in our personal practice. This quality improvement strategy could be easily implemented in every digestive endoscopy unit.

Endoscopic training during fellowship: A nationwide French study: Impact of theoretical courses and simulation-based training during fellowship.

BACKGROUND: In France, it is mandatory that gastroenterology fellows have mastered the basic level of endoscopy by the end of training. The aim of this study was to assess improvement in the quality of fellows' endoscopy training in France during the last four years. METHODS: All fellows in France in training were eligible for participation. A 21-item questionnaire was sent out. The primary outcome was the completion by fourth year fellows of all the number of procedures recommended. Results were compared with those of a 2016 survey. RESULTS: Two-hundred-and-sixty-five fellows responded to the survey. The participation rate was 47.0%. The mean age was 27.3 ± 1.0 years and 56.4% were female. Access to theoretical courses (63.7% vs. 30.6%, p < 0.001) and simulation-based training (virtual reality simulator: 58.4% vs. 28.2%, p < 0.001, animal models: 29.4% vs. 17.2%, p < 0.001) was significantly higher in 2020. Although the number of procedures did not increase, significantly higher perception of skill acquisition in colonoscopy as well as diminished pressure to advance procedures were noted. CONCLUSION: Access to theoretical courses and simulation-based training and perceived acquisition of numerous skills has gotten better. However, the quality of training in endoscopy still needs improvement.

Safety of first year vaccination in children born to mothers with inflammatory bowel disease and exposed in utero to anti-TNFα agents: a French nationwide population-based cohort.

BACKGROUND: Children born to mothers with IBD may be exposed to anti-TNFα agents antenatally. Current European guidelines recommend postponing live vaccines until after 6 months of life in this population. Data on the safety of live vaccines administration in the first year of life of these children are sparse with one reported fatality following bacillus Calmette-Guerin (BCG) administration. AIMS: To describe the use and safety of vaccines administered in children born to mothers with IBD and exposed antenatally to anti-TNFα agents METHODS: Data from children born to mothers with IBD between 2013 and 2014 were collected retrospectively from the French Health Insurance Database. Vaccines recommended before or at 1 year of age were considered. RESULTS: Among 4741 children, 670 (14.1%) were exposed to anti-TNFα agents antenatally, with concomitant thiopurines in 16.0% (n = 107) and steroids in 19.3% (n = 214). Among these 670 children, 315 (47%) were exposed up to delivery. Exposed children were less likely than non-exposed to receive BCG (88/670, 13.1% vs 780/4071, 19.2% respectively, P < .05) and received it later in life (months, mean ± SD, 4.3 ± 3.9 and 2.4 ± 2.9 respectively, P < .001). In exposed children, 64/88 (73%) received BCG vaccination before 6 months of age, but with no BCG-related severe adverse event observed during the first year. Uptake of other vaccines recommended before 6 months was above 85% in both groups. CONCLUSION: In children exposed antenatally to anti-TNFα agents, vaccinations are often not postponed in keeping with the recommendations, but no BCG-related severe adverse events were reported in children vaccinated before 6 months of life.

Assessment of adrenal function in patients with acute hepatitis using serum free and total cortisol.

BACKGROUND: Adrenal dysfunction is frequently reported in severe acute hepatitis using serum total cortisol. AIMS: Because 90% of serum cortisol is bound to proteins that are altered during stress, we investigated the effect of decreased cortisol-binding proteins on serum total and free cortisol in severe acute hepatitis. METHODS: 43 severe and 31 non-severe acute hepatitis and 29 healthy controls were enrolled consecutively and studied prospectively. Baseline (T0) and cosyntropin-stimulated (T60) serum total and free cortisol concentrations were measured. RESULTS: T0 and T60 serum total cortisol did not differ significantly between severe, non-severe hepatitis and healthy controls. Conversely, serum free cortisol (T0p=0.012; T60p<0.001) concentrations increased from healthy controls to severe hepatitis, accompanied by a decrease in corticosteroid-binding globulin and albumin (all p<0.001). In acute hepatitis (n=74), patients with "low" corticosteroid-binding globulin (<28mg/L) had higher T0 serum free cortisol than others (103.1 [61.2-157] vs. 56.6 [43.6-81.9]nmol/L, p=0.0024). Analysis of covariance showed that at equal concentration of total cortisol, the free cortisol concentration was significantly higher in severe than in non-severe hepatitis (p<0.001) or healthy controls (p<0.001). CONCLUSIONS: In severe hepatitis, the decrease in cortisol-binding proteins impairs correct diagnosis of adrenal dysfunction. This could be corrected by measuring or estimating free cortisol.