Minor Endoscopic Sphincterotomy for Recurrent Acute Pancreatitis with Pancreas Divisum

项目摘要 急性胰腺炎是美国住院治疗的最常见胃肠道原因之一。 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（一种不可逆的纤维炎性疾病）的一个强风险因素 这对生活质量有很大影响，也是胰腺癌的一个危险因素。导管内压升高 是诱发急性胰腺炎发作的公认原因。胰腺分裂，见于7-10%的 一般人群，发生在背侧和腹侧胰管不完全融合或不融合时 在早期胚胎发育过程中。使用这个原理，内窥镜医生经常进行内窥镜逆行 胰胆管造影术（ERCP）联合乳头括约肌小切开术（miES）治疗特发性 RAP（iRAP）和胰腺分裂，目的是减少后续发作。这一做法仍然很严重。 有争议的是，由于现有数据的主要局限性，这些数据几乎完全来自小， 回顾性队列研究，结果不一致且主观。这是最高的风险之一 ERCP适应症，ERCP后胰腺炎发生率为10- 20%。一个全面的，精心设计的临床试验 通过充分的随访和盲态治疗分配，显然需要经验性地评估疗效 在iRAP和胰腺分裂的情况下，miES的作用，包括量化这种治疗的累积获益， 干预疾病负担，并研究其与自然史的关系。 利用最近完成的EPISOD试验和NAPS 2的现有基础设施， 提出一项假对照、单盲和盲态结局评估的随机试验， miES对胰腺分裂患者iRAP自然病程的影响。主要结局是 降低随后发生急性胰腺炎的风险（至事件发生时间），次要结局指标为 发作密度的变化、以患者为中心的结局以及慢性胰腺炎的进展。通过具有 有足够的样本量来衡量ERCP的益处，我们将能够明确地确定 ERCP在iRAP合并胰腺分裂患者中的治疗作用将建立一个生物储存库， 急性胰腺炎复发、进展为慢性胰腺炎的新风险因素的未来探索性研究 胰腺炎及其后遗症，以及与对miES反应相关的因素。符合入选标准的患者 但拒绝入组随机试验的患者将被纳入观察队列。不论 结果，这项研究将通过证实或反驳治疗作用对患者护理产生直接影响。 ERCP对iRAP合并胰腺分裂的诊断价值。

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.