Minor Endoscopic Sphincterotomy for Recurrent Acute Pancreatitis with Pancreas Divisum

项目总结 急性胰腺炎是美国住院治疗最常见的胃肠道原因之一。 大约五分之一的急性胰腺炎患者会反复发作。复发性急性胰腺炎 (RAP)是进展为慢性胰腺炎的强烈危险因素，慢性胰腺炎是一种不可逆转的纤维炎症性疾病。 这极大地影响了生活质量，也是胰腺癌的风险因素。导管内压升高 是引发急性胰腺炎的公认原因。胰腺分裂，见于7%-10%的 一般人群，当背侧和腹侧胰管融合不完全或不存在时发生 在早期胚胎发育过程中。根据这一原理，内窥镜医生经常进行内窥镜逆行手术 特发性乳头括约肌小切开术的胰胆管造影术 RAP(IRAP)和胰腺分裂，目的是减少后续攻击(S)。这种做法仍然非常普遍 有争议的是，由于可用数据的主要限制，这些数据几乎完全来自小的， 具有不一致和主观结果的回溯性队列研究。这是最高风险之一 ERCP的适应证，ERCP术后胰腺炎的发生率为10-20%。全面、精心设计的临床试验 有了充分的随访和盲目治疗，显然需要分配来对疗效进行经验性的评估 在iRAP和胰腺分裂的背景下的MIES，包括量化这一累积收益 疾病负担干预及其与自然病史的关系。 利用最近完成的episod试验和NAPS2的现有基础设施，我们 提出一项假对照、单盲、结果评估、随机试验，评估 MIES对胰腺分裂患者iRAP自然病程的影响主要结果是 降低后续急性胰腺炎的风险(事件发生时间)，次要结果衡量标准为 发作密度的变化，以患者为中心的结果，以及进展为慢性胰腺炎。通过拥有 足够的样本量来衡量ERCP的好处，我们将能够最终确定 ERCP在iRAP合并胰腺分裂患者中的治疗作用将建立一个生物信息库，用于 复发性急性胰腺炎进展为慢性胰腺炎的新危险因素的未来探索性研究 胰腺炎及其后遗症，以及与MIES反应相关的因素。符合入选标准的患者 但拒绝参加随机试验的人将被纳入观察队列。而不考虑 结果，这项研究将通过确认或驳斥治疗作用对患者护理产生直接影响 ERCP在iRAP合并胰腺分裂患者中的应用。

Project summary Acute pancreatitis is among the most common gastrointestinal causes for hospitalization in the U.S. Roughly one in five patients with acute pancreatitis will have recurrent bouts. Recurrent acute pancreatitis (RAP) is a strong risk factor for progression to chronic pancreatitis, an irreversible fibroinflammatory disease that greatly impacts quality of life, and is also a risk factor for pancreatic cancer. Increased intraductal pressure is an accepted cause for precipitating an episode of acute pancreatitis. Pancreas divisum, seen in 7-10% of the general population, occurs when the dorsal and ventral pancreatic ducts have incomplete or nonexistent fusion during early embryologic development. Using this rationale, endoscopists often perform endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla sphincterotomy (miES) in patients who have idiopathic RAP (iRAP) and pancreas divisum with a goal to reduce subsequent attack(s). This practice remains highly controversial, due to major limitations in the available data which are derived almost exclusively from small, retrospective cohort studies with inconsistent and subjective outcomes. This is one of the highest risk indications for ERCP, having post-ERCP pancreatitis rates of 10-20%. A full scale, well-designed clinical trial with adequate follow-up and blinded treatment allocation is clearly needed to empirically evaluate the efficacy of miES in the setting of iRAP and pancreas divisum, including quantifying the cumulative benefit of this intervention on disease burden and to study its relationship with its natural history. Capitalizing on the existing infrastructure of the recently completed EPISOD trial and NAPS2, we propose a sham-controlled, single blind with a blinded outcome assessment, randomized trial evaluating the impact of miES on the natural history of iRAP in patients with pancreas divisum. The primary outcome is reducing the risk of subsequent acute pancreatitis (time-to-event), with secondary outcome measures being the change in density of attacks, patient-centered outcomes, and progression to chronic pancreatitis. By having an adequate sample size to measure the benefit of ERCP, we will be able to definitively establish the therapeutic role of ERCP in patients with iRAP and pancreas divisum. A biorepository will be established for future exploratory studies of novel risk factors for recurrent acute pancreatitis, progression to chronic pancreatitis and its sequelae, and factors associated with response to miES. Patients fulfilling the entry criteria but refusing enrollment into the randomized trial will be enrolled into an observational cohort. Irrespective of the outcome, this study will have an immediate impact on patient care by confirming or refuting the therapeutic role of ERCP in patients with iRAP and pancreas divisum.