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.

项目摘要/摘要 食管中神经肌肉功能异常引起的正常吞咽机制中断 身体或下食道括约肌（LES）与显着的发病率和生活质量影响有关， 以及与营养不良，抽吸和癌症有关的死亡率增加。 Achalasia是原型的 食管运动障碍，每100,000次发病率为1-5，患病率为10-20，每100,000次。 不幸的是，阿萨拉氏症的原因尚不清楚，目前的疗法本质上主要是补偿性的 并专注于使用内窥镜扩张或手术肌切开术来破坏LES以改善排空。超过 在过去的5年中，从扩张和手术到每个口腔内镜肌切开术，已经有了进化 （诗）由于其与手术相比与扩张相比，其具有侵入性的方法及其优越的功效。 但是，关于诗的有效性和风险仍然存在的重要问题以及 肌切割方法（位置，长度，深度）在结果上也不清楚。标准诗的肌关节是 通常长8-10厘米，将2-3厘米延伸到卡迪亚，在大约6-7厘米上方 smocamocomartar结，并以透壁或表面方法仅针对 圆形肌肉。我们最近报道说，爆破的肌切开术（BOM）是阿acalasia的常见机制 与沿肌关节部位的局灶性扩张有关的治疗失败严重损害了排空。这 这项研究的科学前提是，当前的诗歌肌关节切开术与 通过对远端食道的影响而偏爱增加的GERD和BOM形成。我们假设 诗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（AIM 1），以检验以下假设：简短量身定制的诗是 不属于标准诗，与较少的回流疾病和BOM形成减少有关。 此外，我们还将旨在更好地了解钉锤食管和痉挛性运动的结果 通过一项严格的前瞻性研究（AIM 2）评估对长期定制的肌切开术的反应。使用 来自研究参与者的数据和样本，我们还旨在完善和验证新的Achalasia患者报告 结果（APRO）度量（AIM 3）并建立生物标本的存储库，以帮助阐明 阿萨拉氏症的病理生理学。这项研究将重塑食管运动障碍的管理 通过与翻译共享标本，提高我们对这些疾病发病机理的理解 科学家专注于神经胃肠病学。