Comparison of EsophyX2.0 and MUSE systems for transoral incisionless fundoplication: Technical aspects and outcomes up to 3 years.

OBJECTIVES: We compared the efficacy and safety of transoral incisionless fundoplication (TIF) with the EsophyX2.0 and MUSE systems for treatment of gastroesophageal reflux disease (GERD). METHODS: TIF outcomes from prospective protocols (Esophy2.0X: 2007-2012; MUSE: 2015-2019) were retrospectively compared regarding technical success, moderate/severe adverse events, morpho-functional findings up to 1 year, and clinical outcomes up to 3 years. Inclusion criteria were: (i) at least 6-month symptomatic GERD, full/partial response to proton pump inhibitors (PPI), esophagitis, and nonerosive reflux disease/hypersensitive esophagus (both protocols); (ii) hiatal hernia <3 cm (Esophy2.0X) and ≤2.5 cm (MUSE); and (iii) Barrett's esophagus <3 cm (MUSE). RESULTS: In the 50 EsophyX2.0 and 46 MUSE procedures, technical success and adverse event rates were similar, but MUSE-related adverse events (4.4%) were life-threatening. At 12 months, hiatal hernia recurred more frequently after EsophyX2.0 (P = 0.008). At 6 months, significantly fewer total and acid refluxes were reported after both TIF, but not more significantly at 1 year. Symptoms improved after both TIF up to 1 year (P < 0.0001), but to a greater extent in MUSE patients up to 3 years (P < 0.0001 vs. P < 0.01 for EsophyX2.0). The rates of 3-year off-PPI therapy patients were 73.5% in the MUSE and 53.3% in the EsophyX2.0 series (P = 0.069). CONCLUSION: Although no conclusion could be drawn from this limited study, the MUSE technique seemed more effective in the long term in patients with hiatal hernia; however, there were more severe adverse events than with EsophyX2.0.

Cost-effectiveness Analysis of Radiofrequency Ablation in Patients With Barrett Esophagus and High-grade Dysplasia or Low-grade Dysplasia.

PURPOSE: Clinical guidelines recommend radiofrequency ablation (RFA) for eradication of Barrett esophagus in patients with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), but evidence on whether RFA provides good value for money is still sparse. This study evaluates the cost-effectiveness of RFA in Italy. METHODS: A Markov model was used to estimate lifelong costs and consequences of disease progression with different treatments. RFA was compared with esophagectomy in the HGD group or endoscopic surveillance in the LGD group. Clinical and quality-of-life parameters were derived from a review of the literature and expert opinions, whereas Italian national tariffs were used as a proxy for costs. FINDINGS: RFA dominated esophagectomy in patients with HGD with a probability of 83%. For patients with LGD, RFA was more effective and more costly than active surveillance (incremental cost-effectiveness ratio, €6276 per quality-adjusted life-year). At a cost-effectiveness threshold of €15,272, the probability of RFA being the optimal strategy in this population was close to 100%. Model results were sensitive to the cost of the interventions and utility weights used in the different disease states. IMPLICATIONS: RFA is likely to be the optimal choice for patients with LGD and HGD in Italy. Italy is discussing the implementation of a national program for the health technology assessment of medical devices, requiring more studies to prove value for money of emerging technologies.

Factors influencing the presence of potentially explosive gases during colonoscopy: Results of the SATISFACTION study.

This study tested the hypothesis that bowel preparation with mannitol should not affect the colonic concentration of H2 and CH4 . Therefore, the SATISFACTION study, an international, multicenter, randomized, parallel-group phase II-III study investigated this issue. The phase II dose-finding part of the study evaluated H2 , CH4 , and O2 concentrations in 179 patients randomized to treatment with 50 g, 100 g, or 150 g mannitol. Phase III of the study compared the presence of intestinal gases in 680 patients randomized (1:1) to receive mannitol 100 g in single dose or a standard split-dose 2 L polyethylene glycol (PEG)-Asc preparation (2 L PEG-Asc). Phase II results showed that mannitol did not influence the concentration of intestinal gases. During phase III, no patient in either group had H2 or CH4 concentrations above the critical thresholds. In patients with H2 and/or CH4 levels above detectable concentrations, the mean values were below the risk thresholds by at least one order of magnitude. The results also highlighted the effectiveness of standard washing and insufflation maneuvers in removing residual intestinal gases. In conclusion, bowel cleansing with mannitol was safe as the concentrations of H2 and CH4 were the same as those found in patients prepared with 2 L PEG-Asc. In both groups, the concentrations of gases were influenced more by the degree of cleansing achieved and the insufflation and washing maneuvers performed than by the preparation used for bowel cleansing. The trial protocol was registered with ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04759885) and with EudraCT (eudract_number: 2019-002856-18).

An Italian prospective multicenter study on colonoscopy practice and quality: What has changed in the last 10 years.

BACKGROUND: A relevant number of adenomas can be missed during colonoscopy. AIMS: Assess the current status of colonoscopy procedures in Italian centers. METHODS: A prospective observational study involving 17 hospitals (34 endoscopists) included consecutive patients undergoing standard colonoscopy. In the first phase, endoscopists performed consecutive colonoscopies. In the second phase, retraining via an online learning platform was planned, while in the third phase data were collected analogously to phase 1. RESULTS: A total of 3,504 patients were enrolled. Overall, a BBPS score ≥6 was obtained in 95.6% of cases (94.8% and 96.9% in the pre- and post-training phases, respectively). 88.4% of colonoscopies had a withdrawal time ≥6 min (88.2% and 88.7% in the pre- and post-training phases). Median adenoma detection rate (ADR) was 39.1%, with no significant differences between the pre- and post-training phases (40.1% vs 36.9%; P = 0.83). In total, 81% of endoscopists had a ADR performance above the 25% threshold. CONCLUSION: High colonoscopy quality standards are achieved by the Italian hospitals involved. Quality improvement initiatives and repeated module-based colonoscopy-training have been promoted in Italy during the last decade, which appear to have had a significant impact on quality colonoscopy metrics together with the activation of colorectal cancer screening programs.

Continuous clinical remission with biologics in ulcerative colitis: the 'AURORA' comparison study.

OBJECTIVES: Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR). METHODS: In a retrospective, multicentre study, all UC patients treated with adalimumab, infliximab biosimilar, golimumab or vedolizumab between 2014 and 2019 were included. All drugs were compared to each other according to the 1-year CCR rate, defined as Mayo partial score ≤2, with bleeding subscore = 0, without any relapse or optimization with dose escalation, topical treatments or steroid use after first clinical remission. RESULTS: Four-hundred sixteen patients (adalimumab = 90, infliximab biosimilar = 105, golimumab = 79, vedolizumab = 142) were included. CCR was achieved in similar percentages among the groups (33%, 37%, 28%, 37%, respectively). All drugs were equivalent in biologic-naive patients, while vedolizumab was better than a second anti-TNFα in prior anti-TNFα agent failures. No differences were found according to type of adverse events or severe adverse events. CONCLUSIONS: Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year. Changing to vedolizumab is more effective than switching to another anti-TNFα in TNFα failures.

Transoral incisionless fundoplication with Medigus ultrasonic surgical endostapler (MUSE) for the treatment of gastro-esophageal reflux disease: outcomes up to 3 years.

BACKGROUND: Transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) is a new intervention for treatment of gastro-esophageal reflux disease (GERD). We aimed at assessing the clinical, functional, and endoscopic effects of TIF by MUSE. METHODS: Forty-six patients underwent TIF. Proton pump inhibitor (PPI) consumption, GERD-health-related quality of life (HRQL) and reflux symptom index (RSI) questionnaires, upper gastrointestinal (GI) endoscopy, esophageal 24-h pH-impedance recording, and high-resolution manometry (HRM) were done before TIF and scheduled 6 and 12 months later (HRM only at 6-month). PPI consumption and symptoms were then assessed yearly. Data up to 3 years are reported in this study (PP- and ITT-analysis). RESULTS: TIF was successfully performed in 45/46 patients; in one patient esophageal intubation was impossible. Perforation occurred in two cases. One patient required surgery within 6 months. Clinical follow-up was available for 42 patients at 6 months and 1 year, 35 patients at 2 years, and 31 patients at 3 years. At 1, 2, and 3 years, PPI consumption was stopped, respectively, in 64.3%, 62.9%, and 74.2% of cases (ITT-analysis: 58.7%, 56.4%, and 65.7%). GERD-HRQL and RSI scores decreased at least 50%, respectively, in 71.5% and 76.2%, 71.4% and 68.6%, and 67.7% of cases (ITT-analysis: 65.2% and 69.6%, 64.1% and 61.5%, and 60%). A significant improvement of both scores was observed up to 3 years. 6-month and 1-year functional follow-up were possible in 31 and 20 patients. HRM showed significant increase of the median lower esophageal sphincter length and rate of peristaltic waves. Esophageal pH-impedance recording found significantly fewer acid, proximal and total refluxes, and percentage of esophageal pH < 4 total time at 6 months, but not at 1 year. CONCLUSION: TIF by MUSE significantly improved symptoms and PPIs consumption up to 3 years. However, esophagitis still persisted in one-third of cases at 1 year and functional improvement at 6 months was not confirmed at 1 year. Severe complications requiring surgery occurred in two cases. CLINICALTRIALS: GOV: ID: NCT03669874.

Long-term outcomes of transoral incisionless fundoplication for gastro-esophageal reflux disease: systematic-review and meta-analysis.

Background and study aims Few reports exist about long-term outcomes of transoral incisionless fundoplication (TIF) for treating refractory gastro-esophageal reflux disease (GERD). Methods A literature search of four major scientific databases was performed up to May 2020 for studies reporting on more than 3-year outcomes of TIF. Data on atient satisfaction, proton pump inhibitor (PPI) daily consumption, PPI use reduction, GERD health-related quality-of-life (GERD-HRQL) score, and normalization of heartburn and regurgitation scores were pooled and summarized with forest plots. Publication bias and heterogeneity were explored. Results Overall, eight studies (418 patients, 232 men; 55.5 %) with a mean follow-up of 5.3 years (range: 3-10 years) were included. The pooled proportion of patient-reported satisfaction before and after TIF was 12.3 % (95 % CI:12.3-35.1 %, I 2  = 87.4 %) and 70.6 % (95 % CI:51.2-84.6, I 2  = 80 %), respectively, corresponding to an odds ratio of 21.4 (95 % CI:3.27-140.5). Pooled rates of patients completely off PPIs and on occasional PPIs were 53.8 % (95 %CI: 42.0 %-65.1 %) and 75.8 % (95 %CI: 67.6-82.6), respectively. The pooled estimated mean GERD-HRQL scores off PPI before and after TIF werey 26.1 (95 %CI: 21.5-30.7; range: 20.0-35.5) and 5.9, respectively (95 %CI:0.35.1-11.4; range: 5.3-9.8; P  < 0.001). The overall pooled rates of heartburn and regurgitation scores normalization were 73.0 % (95 %CI: 0.62-0.82) and 86 %, respectively (95 %CI: 75.0-91.0 %). Conclusion Our study shows that TIF appears to offer a long-term safe therapeutic option for selected patients with GERD who refuse life-long medical therapy or surgery, are intolerant to PPIs, or are at increased surgical risk.

Oral and Fecal Microbiota in Lynch Syndrome.

BACKGROUND: The role of microbiota in Lynch syndrome (LS) is still under debate. We compared oral and fecal microbiota of LS saliva and stool samples with normal healthy controls (NHC). METHODS: Total DNA was purified from feces and saliva to amplify the V3-V4 region of the 16s rRNA gene. Sequences with a high-quality score and length >250 bp were used for taxonomic analysis with QIIME software. RESULTS: Compared to NHC, LS fecal samples demonstrated a statistically significant increase of Bacteroidetes and Proteobacteria and a significant decrease of Firmicutes at the phylum level and of Ruminococcaceae at the family level. Moreover, LS oral samples exhibited a statistically significant increase of Veillonellaceae and Leptotrichiaceae and a statistically significant decrease of Pasteurellaceae. A beta-diversity index allowed differentiation of the two groups. CONCLUSIONS: A peculiar microbial signature is associated with LS, similar to that of sporadic colorectal cancer and Crohn's disease. These data suggest a possible role of proinflammatory bacteria in tumor development in a condition of genetic predisposition, such as LS.

Transoral incisionless fundoplication with an ultrasonic surgical endostapler for the treatment of gastroesophageal reflux disease: 12-month outcomes.

BACKGROUND: Transoral incisionless fundoplication (TIF) with the Medigus ultrasonic surgical endostapler (MUSE) is a new intervention for the treatment of the gastroesophageal reflux disease (GERD). The aim of this study was to assess the 12-month clinical, functional, and endoscopic effects of TIF by MUSE. METHODS: Patients undergoing MUSE completed the GERD-Health Related Quality of Life (GERD-HRQL) and Reflux Symptom Index (RSI) questionnaires, and underwent endoscopy, esophageal 24-hour pH-impedance recording, and high resolution manometry (HRM) before the TIF procedure and 12 months later, or after 6 months for HRM. RESULTS: Among the 37 patients treated, esophageal intubation was not possible in one and esophageal perforation occurred in another. Clinical and endoscopic follow-up at 12 months was completed in 20 patients, with significant improvements in GERD-HRQL, RSI, heartburn, regurgitation scores, and proton pump inhibitor (PPI) consumption observed. One patient required surgery for persisting symptoms. Functional follow-up was possible in 13 patients and showed no significant improvements in the analyzed parameters. CONCLUSIONS: TIF with MUSE significantly improved symptoms at 1-year follow-up, allowing the consumption of PPIs to be stopped or halved in 90 % of patients.

Treatment with rapamycin can restore regulatory T-cell function in IPEX patients.

BACKGROUND: Immune-dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a lethal disease caused by mutations in a transcription factor critical for the function of thymus-derived regulatory T (Treg) cells (ie, FOXP3), resulting in impaired Treg function and autoimmunity. At present, hematopoietic stem cell transplantation is the therapy of choice for patients with IPEX syndrome. If not available, multiple immunosuppressive regimens have been used with poor disease-free survival at long-term follow-up. Rapamycin has been shown to suppress peripheral T cells while sparing Treg cells expressing wild-type FOXP3, thereby proving beneficial in the clinical setting of immune dysregulation. However, the mechanisms of immunosuppression selective to Treg cells in patients with IPEX syndrome are unclear. OBJECTIVE: We sought to determine the cellular and molecular basis of the clinical benefit observed under rapamycin treatment in 6 patients with IPEX syndrome with different FOXP3 mutations. METHODS: Phenotype and function of FOXP3-mutated Treg cells from rapamycin-treated patients with IPEX syndrome were tested by flow cytometry and in vitro suppression assays, and the gene expression profile of rapamycin-conditioned Treg cells by droplet-digital PCR. RESULTS: Clinical and histologic improvements in patients correlated with partially restored Treg function, independent of FOXP3 expression or Treg frequency. Expression of TNF-receptor-superfamily-member 18 (TNFRSF18, glucocorticoid-induced TNF-receptor-related) and EBV-induced-3 (EBI3, an IL-35 subunit) in patients' Treg cells increased during treatment as compared with that of Treg cells from untreated healthy subjects. Furthermore inhibition of glucocorticoid-induced TNF-receptor-related and Ebi3 partially reverted in vitro suppression by in vivo rapamycin-conditioned Treg cells. CONCLUSIONS: Rapamycin is able to affect Treg suppressive function via a FOXP3-independent mechanism, thus sustaining the clinical improvement observed in patients with IPEX syndrome under rapamycin treatment.

Needle-knife fistulotomy vs. standard biliary sphincterotomy for choledocholithiasis: common bile duct stone recurrence and complication rate.

Background and study aims With common bile duct (CBD) stones, access to the CBD can be achieved through the papilla orifice followed by standard biliary sphincterotomy (SBS), or through precut fistulotomy (PF) in case of difficult cannulation. The two methods alter papilla anatomy differently, potentially leading to a different rate of stone recurrence. No data have been published on stone recurrence after PF in patients with CBD stones. The aim of this study was to evaluate CBD stone recurrence, reintervention rate after PF versus SBS, and complications. Patients and methods This was a retrospective single-center cohort study including patients undergoing for the first time endoscopic retrograde cholangiopancreatography (ERCP) for CBD stones with PF in case of failed repeated cannulation attempts, matched for sex/age to patients with SBS randomly extracted from our database. T -test and Fisher's tests were used for continuous and categorical variable comparison. Recurrence probability was calculated with Kaplan-Meier curve. Factors associated with ERCP repetition were evaluated with logistic regression through a Cox's proportional hazards model. Results Eighty-five patients with PF were included, with 85 matched controls (mean age 68.7 years, 45.9 % males). Overall, patients with PF had the same reintervention rate as those with SBS (14.1 % vs. 12.9 %) with a hazard ratio (HR) of 1.11 (95 % CI 0.49 - 2.50; P  = 0.81), but mean time to reintervention was significantly lower (74.9 ±â€Š74.6 vs. 765.6 ±â€Š961.3 days; P  < 0.0001), with 100 % of stones recurring within the first year in the PF group vs. 54.5 % in the SBS group ( P  = 0.01). The only factor associated with ERCP repetition risk was incomplete CBD clearing. Complications, including pancreatitis, did not differ significantly. Conclusions The reintervention rate was significantly higher in the short term after PF. Therefore, closer follow-up in the first 6 to 12 months after ERCP might be appropriate for patients underoing PF.

Inverted "upside-down" esophageal fully-covered self-expanding metal stent is effective for temporary treatment of colorectal strictures: a pilot case series.

Background and study aims Placement of a fully-covered self-expanding metal stent (FC-SEMS) is a valid alternative for benign and malignant colorectal strictures treatment. Despite the reportedly high technical success rate, stenting is still challenging, due to high rates of adverse events. Migration still represents the main issue, although several anti-migration systems have been proposed. Patients and methods Before insertion, esophageal Beta Niti-S FC-SEMSs were inverted and reloaded on the deployment device to invert the proximal and distal parts of the stent, with the largest end placed above the stricture to contrast peristaltic activity. The inverted "upside-down" Beta Niti-S FC-SEMS was placed in five consecutive patients: four pts with benign anastomotic stricture unresponsive to repeated balloon dilation and persisting for at least 10 weeks, and one with malignant rectal neoplasia. In five patients, six inverted FC-SEMSs were placed. Results The modified FC-SEMS did not migrate in 5/6 cases (83 %). Stent migration occurred in the neoplastic case, induced by neoadjuvant chemotherapy. The "upside-down" esophageal Beta Niti-S FC-SEMS stayed in place for an average of 6 weeks, achieving resolution of stricture in all patients but one, who required an additional stent placement, due to incomplete stricture resolution after 6 weeks. Conclusion The inverted esophageal Beta Niti-S FC-SEMSs proved to be effective in treating colorectal stricture in all cases, with no spontaneous migration or significant side effects, and achieved resolution of strictures where a traditional approach, recommended by guidelines, failed.

Transoral incisionless fundoplication with EsophyX for gastroesophageal reflux disease: clinical efficacy is maintained up to 10 years.

Background Transoral incisionless fundoplication with EsophyX is reported to be effective in patients with gastroesophageal reflux disease in short-medium term follow-up. Aim To examine clinical outcomes up to 10 years. Methods In total, 51 procedures were performed in 50 patients. All entered a yearly clinical follow-up schedule including gastroesophageal reflux disease health-related quality-of-life questionnaires, heartburn and regurgitation scores, and daily proton pump inhibitor consumption. Results The procedure was successfully performed in 49/50 patients. Severe complications occurred in 2/51 procedures. The remaining 49 patients were re-evaluated at 2 and 3 years, 41 after 5 years, 30 after 7 years, and 14 after 10 years. Eight patients were lost to follow-up between 3 and 5 years. Seven patients who were unresponsive to endoscopic fundoplication underwent surgical fundoplication. The mean scores at 2 years were significantly lower than before the procedure and did not change substantially during the follow-up. The rates of patients who had stopped or halved antisecretive therapy 2, 3, 5, 7, and 10 years after the procedure were 86.7 %, 84.4 %, 73.5 %, 83.3 %, and 91.7 %, respectively. Conclusions Transoral incisionless fundoplication with EsophyX is an effective therapeutic option for symptomatic gastroesophageal reflux disease patients, with Hill grades I - II or hiatal hernia < 2 cm, who refuse life-long medical therapy or surgery.

Prospective evaluation of ERCP performance in an Italian regional database study.

BACKGROUND: Prospective studies about endoscopic retrograde cholangio-pancreatography (ERCP) in a community setting are rare. AIM: To assess success and complication rates of routinely-performed ERCP in a regional setting, and the priority quality indicators for ERCP practice. METHODS: Prospective region wide observational study on consecutive patients undergoing ERCP during a 6-month period. A centralized online ERCP questionnaire was built and used for data storage. Primary quality indicators provided by the American Society of Gastrointestinal Endoscopy (ASGE) were considered. RESULTS: 38 endoscopists from 18 centers performed a total of 2388 ERCP. The most common indication for ERCP was choledocholitiasis (54.8%) followed by malignant jaundice (22.6%). Cannulation of the desired duct was obtained in 2293 cases (96%) and ERCP was successful in 2176 cases (91.1%). Success and ERCP difficulty were significantly related to the experience of the operator (p = 0.001 and p < 0.001, respectively). ERCP difficulty was also significantly related to volume centers (p < 0.01). The overall complication rate was 8.4%: post-ERCP pancreatitis (PEP) occurred in 4.1% of procedures, bleeding in 2.9%, infection in 0.8%, perforation in 0.4%. Mortality rate was 0.4%. All the ASGE priority quality indicators for ERCP were confirmed. CONCLUSIONS: The procedural questionnaire proved to be an important tool to assess and verify the quality of routinely-performed ERCP performance in a community setting.

G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma detection rate: an international randomized controlled trial (with videos).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged ≥50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial registration number: NCT01917513.).

Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP. METHODS: We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses. RESULTS: Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only. CONCLUSIONS: The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP.