Per-Oral Pyloromyotomy (POP) in the treatment of medical refractory gastroparesis : A randomized, sham-controlled trial

项目总结/摘要： 胃轻瘫是一种慢性的，使人衰弱的胃功能性疾病，其特征在于 胃排空延迟，无机械性梗阻证据。经典病因 胃轻瘫包括特发性、手术后/医源性和糖尿病性。的发生率 胃轻瘫与发达国家的糖尿病流行同时迅速增加。 胃轻瘫的初始管理包括饮食调整和促动力和/或 止吐药物;然而，这些药物往往随着时间的推移而失去疗效，并且通常与 无法忍受的副作用胃轻瘫的手术治疗通常进行一次 最大的药物治疗不再有效并且可以包括胃电刺激， 胃旁路术或胃大部切除术。胃幽门括约肌破裂 （幽门成形术，幽门肌切开术）最近显示出作为保留胃的选择的希望， 不涉及胃切除术所需的显著解剖学重排。经口 幽门肌切开术（POP）是一种新型的内窥镜手术，已显示出有前途的效用， 在几项小型单中心研究中治疗难治性胃轻瘫。这 介入包括通过内窥镜方法分开胃幽门， 完成腹腔镜或开放性幽门环肌切开术相同的功能结局， 开放或腹腔镜手术的侵入性。先前的非比较性回顾性研究 显示胃轻瘫症状改善和胃排空改善。到 迄今为止，尚无前瞻性研究评价该手术的疗效， 与控制程序进行比较。我们的目标是探索POP在生产中的效用 通过经验证的评分评价的胃肠道相关症状的症状缓解 系统（目标1）和通过固相荧光成像测量的目标胃排空 胃排空研究（目的2）。这项研究的创新之处在于， 通过对接受POP与假手术的患者设盲，额外控制安慰剂效应 干预这一贡献将是重要的，因为传统的胃轻瘫疗法不 充分满足临床需求，并支持NIDDK评估新的 临床试验中的治疗选择。POP是一种潜在的干预措施， 与其他手术方式相比，安全性和发病率更低。

PROJECT SUMMARY/ABSTRACT: Gastroparesis is a chronic, debilitating functional disorder of the stomach characterized by a delay in gastric emptying without evidence of mechanical obstruction. Classic etiologies of gastroparesis include idiopathic, post-surgical/iatrogenic, and diabetic. The incidence of gastroparesis is rapidly increasing coinciding with the diabetes epidemic in developed countries. Initial management of gastroparesis includes dietary modifications and prokinetic and/or antiemetic medications; however, these tend to lose efficacy over time and are often associated with intolerable side effects. Surgical therapy for gastroparesis is typically pursued once maximal medical therapy is no longer efficacious and may include gastric electrical stimulation, gastric bypass or subtotal gastrectomy in most cases. Disruption of the gastric pyloric sphincter (pyloroplasty, pyloromyotomy) has recently shown promise as a stomach-preserving option that does not involve the significant anatomical rearrangement required of gastrectomy. Per-oral pyloromyotomy (POP) is a novel endoscopic surgery that has shown promising utility for the management of medically refractory gastroparesis in several small single center studies. This intervention involves the division of the gastric pylorus via an endoscopic approach, accomplishing the same functional outcome of laparoscopic or open pyloromyotomy, without the invasiveness of open or laparoscopic surgery. Prior non-comparative retrospective studies have demonstrated both improvement of gastroparesis symptoms and improved gastric emptying. To date, there have been no prospective studies evaluating the efficacy of this procedure or comparisons to a control procedure. We aim to explore the utility of POP in producing symptomatic relief of gastroparesis-related symptoms as evaluated by validated scoring systems (Objective 1) and objective gastric emptying as measured by solid-phase scintigraphic gastric emptying studies (Objective 2). The proposed research is innovative in that it would additionally control for the placebo effect by blinding patients to receiving POP versus a sham intervention. This contribution would be significant as traditional gastroparesis therapies do not adequately address the clinical need, and supports the mission of the NIDDK to assess new therapeutic options in clinical trials. POP represents a potential intervention with far greater safety profile and less morbidity compared to other surgical modalities.