Defecation mechanisms and subtyping of constipation patients with Fecobionics

摘要 慢性便秘（CC）是一种常见的疾病，影响多达25%的北美人口， 发病率上升，对医疗费用构成重大负担。这种情况的病理生理学是 人们对此知之甚少，因此治疗不足。主要问题有：（1） 对排便反射的不完全理解和2）缺乏生理相关性和实用性 用于识别潜在机制的诊断测试。目前的诊断测试提供不完整的， 往往是相互矛盾的信息。毫不奇怪，这些测试的结果与症状相关性很差， 治疗结果。我们的目标是提供一个更好的理解的机制， 使用新型Fecobionics设备进行映射的健康受试者和CC患者的排便模式 疏散期间的几何和压力分布。Fecobionics是一种电子模拟凳子， 正常粪便的稠度和形状。该装置记录压力、横截面积、方向， 弯曲，形状和粘弹性的直肠和肛管的同时。我们的中央 假设直肠扩张是排便反射的关键组成部分， 目前的诊断测试模式。新型Fecobionics装置将模仿自然排便， 为肛门直肠生理学和病理生理学提供新的机制见解，以促进 开发CC的新治疗方法。Fecobionics可以提供完整的图片正常排便 包括直肠蠕动反射、装置的可变形性和装置的可扩张性的模式（“签名”）。 健康受试者和各种亚型CC患者的肛门括约肌。具体目标为 1）采用Fecobionics法研究正常人的排便动力学。我们将建立 直肠收缩/扩张在正常排泄过程中的作用。2)定义排便模式， 与排便障碍相关的CC患者。我们要确定直肠收缩异常 贡献给CC。3)利用粪仿生学肛门直肠通道的数学模型， 了解正常和异常的排便模式，包括长度-张力特性， 直肠和肛门括约肌我们的建议旨在通过提供一个凳子来改变目前的CC研究 使用一种新的装置来检查排便反射的生理参数的替代物， 直肠和肛管的压力、变形性、生物力学、向量和地形变化。的 将使用无线Fecobionics设备记录所注意到的参数，该设备可以详细检查 健康和疾病中排便反射/过程的机械基础（压力和变形）。的 该项目的影响是，它评估了一种新型、安全、低成本、侵入性较小、低风险、无辐射的器械， 它能够更好地了解疏散和应急机制，从而促进 创新疗法的未来发展。该改进可以导致诊断和治疗方面的改进。 治疗模式，并降低与肛门直肠疾病相关的医疗保健成本。

ABSTRACT Chronic constipation (CC) is a common condition that affects up to 25% of the population in North America with rising incidence that poses a major burden on the healthcare cost. The pathophysiology of this condition is poorly understood and consequently there are inadequate treatments. The significant problems are, 1) incomplete understanding of the defecation reflex and 2) lack of physiologically relevant and practical diagnostic test for identifying the underlying mechanism(s). Current diagnostic tests provide incomplete and often conflicting information. Not surprisingly, results of these tests correlate poorly with symptoms and treatment outcomes. Our objective is to provide an improved understanding of the continence mechanisms and defecation patterns in healthy subjects and patients with CC using a novel Fecobionics device for mapping the geometric and manometric profiles during evacuation. Fecobionics is an electronic simulated stool that has the consistency and shape of normal stool. The device records pressures, cross-sectional area, orientation, bending, shape, and viscoelastic properties of the rectum and anal canal simultaneously. Our central hypothesis is that rectal peristalsis is a key component of the defecatory reflex which is not assessed in the current paradigm of diagnostic testing. The novel Fecobionics device will mimic the natural defecation and provide new mechanistic insights into the anorectal physiology and pathophysiology to facilitate the development of new treatments for CC. Fecobionics can provide complete picture of the normal defecation pattern (“signatures”) that includes rectal peristaltic reflex, deformability of the device and distensibility of the anal sphincters in healthy subjects and patients with various subtypes of CC. The Specific Aims are as follows: 1) Study the defecation dynamics in normal control subjects using Fecobionics. We will establish the role of rectal contraction/peristalsis in the normal evacuation process. 2) Define the defecatory patterns in patients with CC associated with defecatory disorders. We will determine if abnormalities of rectal contraction contribute to the CC. 3) Use a mathematical model of anorectal passage of Fecobionics for enhanced understanding of the normal and abnormal defecatory patterns, including the length-tension properties of the rectum and anal sphincter muscles. Our proposal seeks to shift current CC research by providing a stool surrogate for examining the physiologic parameters of defecation reflex using a novel device that will record, pressure, deformability, biomechanics, vectoral and topographic changes in the rectum and anal canal. The noted parameters will be recorded using a wireless Fecobionics device that can examine in detail the mechanistic underpinnings (stress and deformation) of defecation reflex/process in health and disease. The impact of this project is that it assesses a novel, safe, low cost, less invasive, low-risk, radiation-free device in its ability to provide better understanding of evacuation and continence mechanisms and thereby facilitate future development of innovative therapies. The improvement can lead to improvement in diagnostic and therapeutic modalities and reduce healthcare costs associated with anorectal disorders.