PREcision MEDicine In Achalasia--PREMEDIA

贲门失弛缓症精准医学--PREMEDIA

• 批准号: 10722321
• 负责人: JOHN E PANDOLFINO
• 金额: $ 38.96万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10722321
• 关键词: Achalasia; Address; Adoption; Anatomy; Anxiety; Barium; Biological Specimen Banks; Caring; Clinical; Current Procedural Terminology Codes; Data; Deformity; Deglutition; Dilatation - action; Disease; Distal; Eating; Effectiveness; Endoscopy; Esophageal motility disorders; Esophageal spasm; Esophagectomy; Esophagogastric Junction; Esophagus; Evolution; Functional disorder; Gastroesophageal reflux disease; Guidelines; Impairment; Incidence; Inferior esophageal sphincter structure; Interruption; Length; Malignant Neoplasms; Malignant neoplasm of esophagus; Malnutrition; Manometry; Maps; Measures; Modeling; Morbidity - disease rate; Muscle; Nature; Observational Study; Obstruction; Operative Surgical Procedures; Oral; Outcome; Outcome Measure; Participant; Pathogenesis; Patient Outcomes Assessments; Patients; Phenotype; Physiological; Positioning Attribute; Prevalence; Procedures; Professional Organizations; Prospective Studies; Prospective, cohort study; Psychophysiology; Quality of life; Randomized; Reflux; Reporting; Resolution; Risk; Sampling Studies; Severities; Shapes; Site; Skin; Specimen; Surgical incisions; Symptoms; Techniques; Testing; Thick; Treatment Failure; United States Centers for Medicare and Medicaid Services; Visceral; aspirate; clinical practice; comparative efficacy; efficacy evaluation; electric impedance; improved; improved outcome; in silico; innovation; minimally invasive; mortality; motility disorder; neuromuscular function; novel; personalized approach; precision medicine; primary endpoint; prospective; public health relevance; randomized trial; response; secondary endpoint; spasticity; standard care; stomach cardia; surgical risk; translational scientist; treatment response

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.

项目总结/摘要 食管神经肌肉功能异常导致正常吞咽机制中断 身体或下食管括约肌（LES）与显著的发病率和生活质量影响相关， 以及与营养不良、误吸和癌症有关的死亡率增加。贲门失弛缓症是 食管动力障碍，发病率为1-5/100，000，患病率为10-20/100，000。 不幸的是，贲门失弛缓症的原因是未知的，目前的治疗主要是补偿性质的 并专注于破坏LES，以改善排空，使用内窥镜扩张或手术切开术。超过 在过去的5年里，已经从扩张和手术发展到经口内镜下肌切开术 （POEM），因为其与手术相比侵入性更小，且其与扩张相比具有上级功效。 然而，关于POEM的有效性和风险的重要问题仍然存在， 肌切开术入路（位置、长度、深度）对结局的影响也不清楚。标准POEM肌切开术是 通常长度为8-10 cm，延伸到贲门内2-3 cm，并在贲门上方约6-7 cm。 鳞状柱状连接处，采用透壁或浅表入路，仅针对 环状肌我们最近报道，吹出肌切开术（BOM）是一种常见的机制失弛缓症 治疗失败与肌切开术部位沿着的局灶性扩张相关，严重损害排空。的 这项研究的科学前提是，目前在POEM中进行肌切开术的任意方法与 通过其对远端食管的影响，更倾向于增加GERD和BOM的形成。我们假设 POEM的创新精确方法可以改善结果并减少并发症。因此我们 正在提出一项多中心随机试验（目标1），以检验一个简短的假设，定制的POEM将 不劣于标准POEM，并且与反流疾病较少和BOM形成减少相关。 此外，我们还将旨在更好地了解手提钻食管和痉挛性运动的结果 通过一项严格的前瞻性研究（目标2）评估对长期定制的肌切开术的反应。使用 从研究参与者的数据和样本，我们还旨在完善和验证一个新的贲门失弛缓症患者报告 结果（APRO）措施（目标3），并建立一个生物标本库，以帮助阐明 贲门失弛缓症的病理生理学。这项研究将重塑食管动力障碍的管理， 通过与翻译人员共享标本，提高我们对这些疾病发病机制的理解 专注于神经胃肠病学的科学家