RESUMO
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.
Assuntos
Pancreatite Crônica , Tripsinogênio , Humanos , Alelos , Variações do Número de Cópias de DNA/genética , Predisposição Genética para Doença , Genótipo , Mutação , Pancreatite Crônica/genética , Tripsina/genética , Tripsinogênio/genéticaRESUMO
INTRODUCTION: Early reports of endoscopic submucosal dissection (ESD) in Europe suggested high complication rates and disappointing outcomes compared to publications from Japan. Since 2008, we have been conducting a nationwide survey to monitor the outcomes and complications of ESD over time. MATERIAL AND METHODS: All consecutive ESD cases from 14 centers in France were prospectively included in the database. Demographic, procedural, outcome and follow-up data were recorded. The results obtained over three years were compared to previously published data covering the 2008-2010 period. RESULTS: Between November 2010 and June 2013, 319 ESD cases performed in 314 patients (62% male, mean (±SD) age 65.4 ± 12) were analyzed and compared to 188 ESD cases in 188 patients (61% male, mean (±SD) age 64.6 ± 13) performed between January 2008 and October 2010. The mean (±SD) lesion size was 39 ± 12 mm in 2010-2013 vs 32.1 ± 21 for 2008-2010 (p = 0.004). En bloc resection improved from 77.1% to 91.7% (p < 0.0001) while R0 en bloc resection remained stable from 72.9% to 71.9% (p = 0.8) over time. Complication rate dropped from 29.2% between 2008 and 2010 to 14.1% between 2010 and 2013 (p < 0.0001), with bleeding decreasing from 11.2% to 4.7% (p = 0.01) and perforations from 18.1% to 8.1% (p = 0.002) over time. No procedure-related mortality was recorded. CONCLUSIONS: In this multicenter study, ESD achieved high rates of en bloc resection with a significant trend toward better outcomes over time. Improvements in lesion delineation and characterization are still needed to increase R0 resection rates.