Defecation mechanisms and subtyping of constipation patients with Fecobionics

点击翻译按钮获取中文摘要

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.