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Volume 4, Supplement 2, 2004

Volume 4, Supplement 2, 2004

Table of Contents

Definitions, Epidemiology, and Impact of Chronic Constipation
Constipation, however it is defined, is a common problem in the community. The exact prevalence of constipation depends on the definition used; prevalence estimates range from 2% to 28%. The prevalence of constipation has been stable because the onset and disappearance rates over time are similar, but accurate data on the incidence of constipation are lacking. Approximately one third of those individuals with constipation seek health care; this is an expensive fraction due to investigational and medication costs. The evidence that life-style factors are causally linked to constipation is weak, although nonsteroidal anti-inflammatory drug use and the use of other constipation-inducing medications are important risk factors. Constipation is not of clinical importance until it causes physical risks or impairs quality of life. There is accumulating evidence that self-reported constipation and functional constipation as defined by the Rome Criteria lead to significant impairment of quality of life, with the implication that this is a serious condition in the majority of people afflicted. Constipation may have other serious consequences; an increased risk of colon cancer has been reported but could be explained by confounding. Although hemorrhoids have been attributed to constipation, this association has been questioned. The costs of testing in patients presenting with constipation has been conservatively estimated to be 6.9 billion dollars annually in the United States; treatment costs add substantially to the health care burden. [Rev Gastroenterol Disord. 2004;4(suppl 2):S3-S10]
Subtypes of Constipation: Sorting Out the Confusion
In patients with chronic constipation, identifying subtypes based on underlying physiology guides subsequent therapeutic choices. Chronic constipation subtypes include slow-transit constipation, pelvic floor dyssynergia, functional constipation, and irritable bowel syndrome with constipation. Chronic constipation subtypes are defined by the result of colonic transit, pelvic floor function, and the presence or absence of significant abdominal pain. Although a variety of tests are available, the most straightforward approach uses the 5-day colonic marker test of transit and anorectal manometry with balloon expulsion testing to evaluate for pelvic floor dysfunction. Patients with normal physiologic tests have either irritable bowel syndrome with constipation or normal-transit constipation. Significant overlap exists between subtypes and a clear distinction is not always possible, with up to a 50% overlap between patients with slowtransit constipation and irritable bowel syndrome, approximately 10% of patients evaluated exhibiting both slow transit and pelvic floor dyssynergia, and 50% of patients with pelvic floor dyssynergia also found to have slow transit. Symptom severity assessment provides the rationale for pursuing further testing and directing the aggressiveness of treatment as patients with greater symptom severity have reduced quality of life and poor physical functioning scores. Few constipation-specific validated measures exist for measuring symptom severity in chronic constipation. In clinical practice severity may be defined as mild symptoms having minimal impact upon daily activities or moderate to severe symptoms that increasingly interfere with daily life. [Rev Gastroenterol Disord. 2004;4(suppl 2):S11-S16]
Pathogenesis of Slow Transit and Pelvic Floor Dysfunction: From Bench to Bedside
The colon and anorectum function together to provide intraluminal mixing, absorption of water, electrolytes, and short chain fatty acids, dehydration of fecal material, storage, and ultimately, elimination in a socially appropriate manner. Normal function and continence require accommodation of the colon and rectum to the entry of fecal materials, which includes receptive relaxation, perception, and discrimination of rectal contents, and voluntary and reflex motor function of the anorectum. Defecation, on the other hand, requires the reflex relaxation of the internal anal sphincter, voluntary and reflexive relaxation of the external anal sphincters and pelvic floor structures, and adequate rectosigmoid tone to allow funneling of contents through the anal canal. The sensation of urgency with rectal filling, and the motivation and prior learning of the appropriate responses are also required. Continence and defecation, therefore, involve complex sensory, structural, and motor mechanisms that involve both the colon and pelvic floor. These mechanisms and their relative importance to the pathogenesis of slow-transit constipation and pelvic floor dysfunction will be reviewed. [Rev Gastroenterol Disord. 2004:4(suppl 2):S17-S27]
Diagnosis of Constipation in Primary and Secondary Care
The evaluation of chronic constipation involves a careful delineation of its duration and characteristics as well as a physical examination including neurologic, anorectal, and perineal assessment. In patients who fail to respond to fiber supplements or simple laxatives, diagnostic studies such as barium radiography, rectal biopsy, and colonic transit studies may be warranted. Studies of defecation and anorectal function may be useful in those who complain of excessive straining or who use digital manipulation to facilitate evacuation. Most patients, however, do not require diagnostic studies beyond a careful history and physical examination, and are easily managed in the primary care setting. [Rev Gastroenterol Disord. 2004;4(suppl 2):S28-S33]
Current Treatment Options for Chronic Constipation
Various agents are used for the medical management of chronic constipation but few have been carefully studied. This review examines available data concerning several bulk and fiber products, lubricating agents, stimulants, and osmotic laxatives, alone and in combination. Popular therapeutic options for initial treatment of chronic constipation are dietary fiber and medicinal bulk. Subsequent treatments if fiber is not successful or tolerated would include saline osmotic laxatives, lactulose, or stimulants like senna or bisacodyl. Recent data demonstrate polyethylene glycol laxative to be safe and effective as an initial or second-line agent for chronic constipation. Indications and use of surgery and biofeedback are also discussed. [Rev Gastroenterol Disord. 2004;4(suppl 2):S34-S42]
New and Emerging Treatment Options for Chronic Constipation
Chronic constipation remains a therapeutic challenge for today’s physicians. Traditional approaches include use of fiber, osmotic laxatives, stimulant laxatives, prokinetic agents, biofeedback training, and surgery. These often are tried sequentially and episodically and have little evidence of long-term efficacy. Patients often report inadequate relief of symptoms. There is room for improvement, therefore, in the therapy of chronic constipation. Future advances largely will be based on insights into the enteric nervous system (ENS), the structure and function of which is being revealed in great detail. Manipulating the ENS pharmacologically offers the opportunity to reprogram this key control system to improve bowel function. For example, interneurons in the ENS display 5-HT4 receptors, activation of which enhances the peristaltic reflex. Prokinetic agents that stimulate those receptors, such as tegaserod and prucalopride, have demonstrated efficacy as investigational agents for the treatment of chronic constipation in large studies. Less well studied investigational drugs with presumed activity in the ENS include opiate antagonists and the nerve growth factor neurotrophin-3. Both of these types of agents have been shown to be effective in small groups of patients with constipation. Another approach under development is to stimulate colonic fluid secretion by opening chloride channels in the epithelium pharmacologically. Existing nonpharmacological treatments that can be improved include biofeedback training for pelvic floor dysfunction and surgery. Future developments include investigation of electrical stimulation of the colon and use of stem cells to repopulate degenerated populations of neurons, interstitial cells of Cajal, or smooth muscle cells [Rev Gastroenterol Disord. 2004;4(suppl 2):S43-S51]