PREcision MEDicine In Achalasia--PREMEDIA

项目摘要/摘要 食道神经肌肉功能异常导致正常吞咽机制的中断 身体或下食道括约肌(LES)与显著的发病率和生活质量影响有关， 以及与营养不良、吸入和癌症有关的死亡率增加。失弛缓症是典型的 食道动力障碍的发病率为1-5/10万，患病率为10-20/10万。 不幸的是，失弛缓症的病因尚不清楚，目前的治疗主要是代偿性的。 并专注于通过内窥镜扩张或外科肌切开术破坏LES以改善排空。完毕 在过去的5年里，已经从扩张术和外科手术向经口腔内窥镜肌切开术发展 (POEM)由于其与手术相比侵入性更小，与扩张术相比其疗效更好。 然而，关于诗歌的有效性和风险以及诗歌的影响的重要问题仍然存在。 肌切开入路(位置、长度、深度)对结果的影响也不清楚。标准诗《肌肉切割法》是 通常长8-10厘米，伸入心内2-3厘米，上方约6-7厘米 鳞状突交界处，可采用穿壁或浅层入路，仅针对 环状肌肉。我们最近报道，膨胀式肌切开术(BOM)是贲门失弛缓症的常见机制 治疗失败与肌切开处的局部扩张有关，严重影响排空。这个 这项研究的科学前提是，目前对诗歌中肌切开术的武断方法与一种 倾向于通过其对远端食道的影响而增加GERD和BOM的形成。我们假设 使用POEM的创新精确方法可以改善结果并减少并发症。因此，我们 正在提议一项多中心随机试验(目标1)来检验这样一种假设，即一首短的、量身定做的诗将是 不劣于标准的POSE，与较少的反流病和BOM的形成减少相关。 此外，我们还将致力于更好地了解手提钻食道和痉挛运动的结果。 通过严格的前瞻性研究(目标2)评估长期定制肌切开术的反应。vbl.使用 来自研究参与者的数据和样本，我们还旨在提炼和验证报告的一名新的贲门失弛缓症患者 结果(APRO)衡量(目标3)并建立生物标本储存库，以帮助阐明 失弛缓症的病理生理学。这项研究将重塑食道动力障碍的管理和 通过与翻译人员分享标本来提高我们对这些疾病发病机制的理解 科学家们专注于神经胃肠病学。

PROJECT SUMMARY/ABSTRACT An interruption in the normal swallowing mechanism due to abnormal neuromuscular function in the esophageal body or the lower esophageal sphincter (LES) is associated with significant morbidity and quality of life impact, as well as increased mortality related to malnutrition, aspiration and cancer. Achalasia is the prototypical esophageal motility disorder and has an incidence of 1-5 per 100,000 and a prevalence of 10-20 per 100,000. Unfortunately, the cause of achalasia is unknown and the current therapies are primarily compensatory in nature and focus on disrupting the LES to improve emptying using either endoscopic dilation or surgical myotomy. Over the last 5 years, there has been an evolution away from dilation and surgery toward per oral endoscopic myotomy (POEM) due to its less invasive approach compared to surgery and its superior efficacy compared to dilation. However, important questions regarding the effectiveness and risks of POEM remain and the impact of the myotomy approach (position, length, depth) on outcomes is also unclear. The standard POEM myotomy is typically 8-10 cm in length, extending 2-3 cm into the cardia and approximately 6-7 cm above the squamocolumnar junction and it is performed with either a transmural or superficial approach targeting only the circular muscle. We recently reported that blown out myotomy (BOM) is a common mechanism of achalasia treatment failure related to focal dilatation along the myotomy site that profoundly impairs emptying. The scientific premise of this study is that the current arbitrary approach to myotomy in POEM is associated with a predilection to increased GERD and BOM formation through its effects on the distal esophagus. We hypothesize that an innovative precision approach with POEM can improve outcomes and reduce complications. Thus, we are proposing a multicenter randomized trial (Aim 1) to test the hypothesis that a short, tailored POEM will be non-inferior to the standard POEM and associated with less reflux disease and a reduction in BOM formation. Additionally, we will also aim to better understand outcomes in jackhammer esophagus and spastic motility disorders through a rigorous prospective study (Aim 2) assessing response to a long tailored myotomy. Using data and samples from study participants, we also aim to refine and validate a new Achalasia Patient Reported Outcome (APRO) measure (Aim 3) and establish a repository of biological specimens to help elucidate the pathophysiology of achalasia. This study will reshape the management of esophageal motility disorders and improve our understanding of the pathogenesis of these disorders by sharing specimens with translational scientists focused on neurogastroenterology.