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.

Comparison of 20-gauge Procore® and 22-gauge Acquire® needles for EUS-FNB of solid pancreatic masses: an observational study.

Background and Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) has been proposed to obtain high-quality tissue samples for pancreatic tumors. We performed an observational study to compare EUS-FNB with a 20-gauge Procore® needle versus a 22-gauge Acquire® needle. Our primary endpoint was the quantity of the obtained tissue, as defined by the mean cumulative length of tissue core biopsies per needle pass. Methods: Sixty-eight EUS-FNB were consecutively performed on patients with a pancreatic mass. The choice of needle depended on availability at the time of admission: 34 punctures were performed with each needle. Histological material was studied in a blinded manner with respect to the needle, and the cumulative length of tissue core biopsies per needle pass was determined. Intraobserver and interobserver variability of this criterion was then evaluated. Results: There were no between-group differences. Histological diagnosis was achieved and core biopsy specimens were obtained in 28 out of 34 patients (82%) in the 20-gauge Procore® group and in 33 out of 34 patients (97%) in the 22-gauge Acquire® group (p = .1). The mean cumulative length of tissue core biopsies per needle pass was significantly higher with the 22-gauge Acquire® needle with 8.2 ± 4.2 mm versus 4.2 ± 3.8 mm for the 20-gauge Procore® needle (p < .01). No intra and inter-observer variability of this criterion was observed. Conclusions: Our results suggest significant differences, with a mean cumulative length of tissue core biopsies per needle pass significantly higher with the 22-gauge Acquire® needle. This simple criterion seems reliable and reproducible.

Features of Autoimmune Pancreatitis Associated With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Few people know of autoimmune pancreatitis (AIP), a rare disorder associated with inflammatory bowel diseases (IBD). We aimed to describe phenotype and outcomes of IBD and AIP when associated. METHODS: We performed a retrospective study of cases of AIP in IBD identified from the multicenter Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif in Belgium and France from July 2012 through July 2015. Patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria for AIP. A definitive AIP diagnosis was based on histological analysis of pancreatic resection specimens or samples collected by fine-needle aspiration during endoscopic ultrasound. Patients with probable type 1 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, level of serum immunoglobulin G4, and involvement of other organs. Patients with probable type 2 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, and association with IBD. The primary objective was to collect information on the characteristics of AIP in patients with IBD. We also compared features of patients with IBD with and without AIP in a case-control analysis, using multivariate analysis. RESULTS: We analyzed data from 91 individuals with AIP and IBD (47 women) seen at 23 centers (58 had ulcerative colitis [UC] and 33 Crohn's disease [CD]). Eighty-nine patients had type 2 AIP, and 2 patients had type 1 AIP. The mean age at diagnosis of AIP was 35 ± 12 years, and for IBD it was 32 ± 12 years. AIP preceded IBD in 19 patients (21%). Over a mean follow-up period of 5.7 ± 4.9 years, 31 patients (34%) relapsed, 11 patients (12%) developed diabetes, and 17 patients (19%) developed exocrine pancreatic insufficiency. In patients with UC, factors independently associated with AIP included proctitis (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.3; P = .007) and colectomy (OR, 7.1; 95% CI, 2.5-20; P = .0003). In patients with CD, AIP was significantly associated with fewer perianal lesions (OR, 0.16; 95% CI, 0.03-0.77; P = .023), non-stricturing non-penetrating CD (OR, 6.7; 95% CI, 1.25-33.3; P = .0029), and higher rate of colectomy (OR, 27.8; 95% CI, 3.6-217; P = .0029). CONCLUSIONS: In a multicenter retrospective analysis of patients with AIP and IBD, followed for an average of 5.7 ± 4.9 years, we found most to have type 2 AIP. Two-thirds of patients have UC, often with proctitis. One-third of patients have CD, often with inflammatory features. Patients with IBD and AIP have higher rates of colectomy than patients with just IBD.

Microscopic colitis or functional bowel disease with diarrhea: a French prospective multicenter study.

OBJECTIVES: To describe the characteristics of a cohort of patients with microscopic colitis (MC; lymphocytic (LC) or collagenous (CC) colitis) and to compare them with patients with functional bowel disorder with diarrhea (FBD-D). METHODS: Between September 2010 and June 2012, patients fulfilling the following inclusion criteria were prospectively included in 26 centers in France: (i) having at least three bowel movements daily with change in stool consistency; (ii) duration of abnormal bowel habit >4 weeks; and (iii) normal or near-normal colonoscopy. Each patient underwent a colonoscopy and colonic biopsies. We compared the demographic, clinical, biological, and etiological characteristic of patients with MC (CC and LC) with those of control patients with FBD-D. RESULTS: A total of 433 patients were included: 129 with MC (87 LC and 42 CC), 23 with another organic disease, and 278 with FDB-D, including patients with diarrhea and abdominal pain who met the criteria of Rome III (irritable bowel syndrome with diarrhea) and patients with functional diarrhea without abdominal pain. Logistic regression analysis identified the following independent predictors of MC: age >50 years (odds ratio (OR)=3.1, 95% confidence interval (CI)=1.6-5.9), presence of nocturnal stools (OR=2, 95% CI=1.1-3.9), weight loss (OR=2.5, 95% CI=1.3-4.7), duration of diarrhea <12 months (OR=2.0, 95% CI=1.1-3.5), recent introduction of new drugs (OR=3.7, 95% CI=2.1-6.6; P<0.0001), and the presence of a known autoimmune disorder (OR=5.5, 95% CI=2.5-12). CONCLUSIONS: Age >50 years, the presence of nocturnal stools, weight loss, the introduction of a new drug, and the presence of a known autoimmune disease increase the probability of MC and thus the indication for colonoscopy with biopsies.

Hepatitis B Delta: assessment of the knowledge and practices of hepato-gastroenterologists practicing in non-academic settings in France.

BACKGROUND: Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. OBJECTIVE: We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. METHODS: A Google form document was sent to those HGs from May to September 2021. RESULTS: A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. CONCLUSION: Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.

Over 90% of cases of Microscopic Colitis can be diagnosed by performing a short colonoscopy.

AIMS: To determinate the topographical distribution of key diagnostic histological features of lymphocytic colitis (LC) and collagenous colitis (CC) and to establish what correlations may exist between the histological findings and the causes and severity of MC. PATIENTS AND METHODS: Patients with MC were included in a prospective multicentre French study from September 2010 to October 2012. MC was diagnosed by performing total colonoscopy with multiple biopsies of the rectum and colon collected in separate jars and analyzed separately for each site (descending and sigmoid colon, transverse colon, ascending colon). CC was defined as a subepithelial collagen layer>10µm thick and LC as an intraepithelial lymphocyte (IEL) count>20 lymphocytes per 100 epithelial cells without any associated thickening of the subepithelial collagen. RESULTS: Ninety-five patients, 69 with LC 26 and with CC, were included in the analysis. The sensitivity of the biopsies for diagnosing MC was maximum in the transverse colon and minimum in the rectum. Rectal and left colonic biopsies resulted in the diagnosis of CC and CL in 93% and 94% of cases, respectively. All the remaining cases of MC were diagnosed by performing additional biopsies beyond the splenic flexure. In patients with LC, a higher rate of IELs was associated with the absence of abdominal pain (P=0.01) and a shorter duration of diarrhea (P=0.001). In patients with CC, a lower level of collagen thickness in the basement membrane was associated with the presence of an autoimmune disease (P=0.02). CONCLUSION: More than 90% of cases of microscopic colitis were diagnosed in this study by performing rectal and left colonic biopsies.

Middle-term mortality and re-bleeding after initial diverticular bleeding: A nationwide study of 365 mostly elderly French patients.

BACKGROUND AND AIMS: The aim of this study was to determine the mortality and re-bleeding rates, and the risk factors involved, in a cohort of patients with previous diverticular bleeding (DB). METHODS: In 2007, data on 2462 patients with lower gastrointestinal (GI) bleeding were collected prospectively at several French hospitals. We studied the follow-up of patients with DB retrospectively. The following data were collected: age, mortality rates and re-bleeding rates, drug intake, surgery and comorbidities. RESULTS: Data on 365 patients, including 181 women (mean age 83.6 ± 9.8 years) were available. The median follow-up time was 3.9 years (IQR 25-75: 1.7-5.4). Of these, 148 patients died (40.5%). Among the 70 patients (19.2%) who had at least one re-bleeding episode, nine died and three underwent surgical procedures. Anticoagulation and antiplatelet therapy was discontinued in 70 cases (19.2%). The independent risk factors contributing to mortality were age > 80 years (HR = 3.18 (2.1-4.9); p < 0.001) and a Charlson comorbidity score > 2 (1.91 (1.31-2.79); p = 0.003). Discontinuation of therapy was not significantly associated with a risk of death due to cardiovascular events. No risk factors responsible for re-bleeding were identified, such as antiplatelet and anticoagulant therapy in particular. CONCLUSIONS: In this cohort, the rates of mortality and DB re-bleeding after a median follow-up time of 3.9 years were 19.2% and 40.5%, respectively. The majority of the deaths recorded were not due to re-bleeding.

High prevalence of deficient mismatch repair phenotype and the V600E BRAF mutation in elderly patients with colorectal cancer.

AIMS: Colorectal cancer (CRC) occurs mostly in the elderly. However, the biology of CRC in elderly has been poorly studied. This study examined the prevalence of deficient mismatch repair phenotype (dMMR) and BRAF mutations according to age. PATIENTS AND METHODS: MMR phenotype was prospectively determined by molecular analysis in patients of all ages undergoing surgery for CRC. BRAF V600E mutation status was analysed in a subset of dMMR tumours. RESULTS: A total of 754 patients who underwent surgery between 2005 and 2008 were included in the study. Amongst them, 272 (36%) were ≥75years old. The proportion of women <75 was 38% and that ≥75 was 53% (p<0.0001). The prevalence of dMMR was 19.4% in patients ≥75 and 10.7% in patients <75 (p=0.0017). For patients ≥75, the prevalence of dMMR was significantly higher in women than in men (27% vs 10.2%, respectively; p=0.003) but was similar in women and men <75 (12.5% vs 9.7%, respectively; p=0.4). We examined BRAF mutation status in 80 patients with dMMR tumours. The V600E BRAF mutation was significantly more frequent in patients ≥75 than in patients <75 (72.2% vs 11.4%, respectively; p<0.001). In patients ≥75, there was no difference in the prevalence of the BRAF V600E mutation according to sex (78% in women and 70% in men, p=0.9). CONCLUSIONS: The prevalence of dMMR in CRC is high in patients over 75. In elderly patients, dMMR tumours are significantly more frequent in women than in men. The BRAF mutation is frequent in elderly patients with CRC.

Klebsiella oxytoca as an agent of antibiotic-associated hemorrhagic colitis.

BACKGROUND & AIMS: Klebsiella oxytoca has been isolated from stools and colonic biopsy specimens of patients with Clostridium difficile-negative antibiotic-associated hemorrhagic colitis (AAHC), but the pathogenic role of the germ has not been established. The purpose of this study was to investigate the presence of K. oxytoca in patients with AAHC from a prospective cohort of patients with acute colitis, and to test the cytotoxicity on HEp-2 cells of K. oxytoca strains from patients with AAHC and healthy carriers. METHODS: Colonic biopsy specimens and a sample of colonic fluid from 93 consecutive patients with acute colitis were cultured on selective media for 7 established pathogens and K. oxytoca. The 2 K. oxytoca strains isolated in the 4 patients with C. difficile-negative AAHC of this cohort and 105 additional K. oxytoca strains from patients with C. difficile-negative AAHC (n = 15) and healthy carriers (n = 90) were tested for cytotoxicity using a HEp-2 cell culture assay. RESULTS: K. oxytoca was isolated in 50% (2 of 4) of the patients of the prospective cohort with C. difficile-negative AAHC compared with 2% (1 of 41) of the patients with acute colitis caused by established pathogens (P = 0.02). The rate of cytotoxic strains of K. oxytoca was higher in patients with AAHC (82%) than in healthy carriers (42%, P = 0.003). CONCLUSIONS: We conclude that K. oxytoca is isolated with a significant high rate in patients with C. difficile-negative AAHC, and that K. oxytoca strains from patients with AAHC are cytotoxic more frequently on HEp-2 cells than strains from healthy carriers. These results strengthen the hypothesis of a causative role of K. oxytoca in some of the patients with AAHC.