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

International audienceBACKGROUND: 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

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

Pancreatology

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

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

International audienc