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OBJECTIVES: The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNß3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNß3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy. METHODS: Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNß3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods. RESULTS: GNß3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy-Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNß3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43). CONCLUSIONS: GNß3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.

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BACKGROUND & AIMS: Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. METHODS: We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. RESULTS: An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life. CONCLUSIONS: Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.

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Gastrointestinal causes of abdominal pain are numerous. These causes are reviewed in brief here, divided into 2 categories: acute abdominal pain and chronic abdominal pain. They are further subcategorized by location of pain as it pertains to the abdomen.

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BACKGROUND: Functional dyspepsia (FD) is a common problem affecting up to 10-25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment. OBJECTIVES: The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD. DESIGN: The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNß3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo. METHODS: The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651).

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Barrett's esophagus (BE) results from prolonged uncontrolled gastroesophageal reflux (GERD). Patients at risk for BE should be screened with upper endoscopy. Dysplasia is identified pathologically on endoscopic biopsy. The finding of low grade dysplasia indicates the need for more surveillance. High grade dysplasia warrants intervention with ablative techniques or surgery due to the extremely high rate of malignant transformation to esophageal adenocarcinoma. All patients should receive measures to control GERD (life-style modifications and acid suppression).

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Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. In 2008, screening recommendations for CRC were updated. Successful reduction in CRC prevalence and deaths depends on a thorough understanding and correct implementation of these guidelines. This paper reviews the most recent CRC screening guidelines, in order to promote increased screening and effective adherence to these guidelines.

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Constipation is a common complaint in pregnancy. Its symptoms may include infrequent defecation, hard or scybalous stool, or excessive straining. An extensive evaluation is usually unnecessary for women who present with constipation for the first time during pregnancy. Most patients respond to dietary measures or simple laxatives. Few laxatives have been evaluated in clinical trials for use in pregnancy. Evidence supports treatment with fiber supplements and senna. The use of a pharmacologic agent for treatment of constipation during pregnancy must be weighed against possible adverse effects. Most laxatives carry a pregnancy category B or C classification. First-line therapy includes increasing fiber intake through diet or supplements. Osmotic laxatives may be beneficial for some patients. The short-term use of osmotic or stimulant laxatives is generally reserved for patients who fail to respond to dietary changes or bulking agents.

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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 slow-transit 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.

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BACKGROUND & AIMS: The impact of education on irritable bowel syndrome (IBS) is not well known. This study evaluated the effect of a onetime group education program on patient-based outcomes in IBS. METHODS: All adults referred by Mayo Clinic physicians to the Gastroenterology Division with a diagnosis of IBS between May 1997 and March 1998 were asked to participate. Questionnaires were administered at baseline and 6 months. Symptom resolution, change in pain severity, quality of life, Health-Promoting Lifestyle Profile score, overall patient satisfaction, and health care utilization were compared among those patients who attended the multidisciplinary class and those who did not. RESULTS: Of the 506 patients approached, 403 (80%) agreed to participate. The clinical diagnosis was confirmed in 344 patients (85%) on chart review; 211 patients (61%) subsequently completed a follow-up questionnaire. Overall, 29% of class attendees who met Rome criteria for IBS at baseline no longer met Rome criteria at follow-up, compared with 7% of nonattendees. By multivariate analysis, class attendance predicted higher odds of not meeting Rome criteria at follow-up in individuals meeting Rome criteria at baseline (odds ratio, 7.91; 95% confidence interval, 0.97-64.41) than in nonattendees, but the opposite effect was seen with class attendance in those not meeting Rome criteria at baseline. This interaction between baseline Rome status and class attendance was significant (P < 0.05). Class attendance was associated with improvement in Health-Promoting Lifestyle Profile scores (P < 0.05) but not with change in pain, quality of life, satisfaction, or health care utilization. CONCLUSIONS: A onetime, multidisciplinary class for patients with IBS was associated with improvement in symptoms and health-promoting lifestyle behavior.

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Identification of physiologic factors that predict response to fecal incontinence therapy would be helpful in choosing the optimal treatment and advising patients on the likelihood of a successful outcome. However, few physiologic parameters have been consistently identified as important in predicting response to either biofeedback or surgery. The process of isolating these factors has been hampered by heterogeneity in the definition of fecal incontinence, lack of consensus on what constitutes a successful outcome, lack of follow-up data, variations in the way "standard" treatments are implemented, and lack of properly powered randomized controlled trials. Among the physiologic variables that studies have generally found to be predictive of successful outcomes in biofeedback treatment are the threshold for external anal sphincter contraction after treatment, the inclusion of sensory training in treatment, and a reduction in volume for the first sensation after treatment. Factors that have not been found to be important in predicting outcome following biofeedback retraining include the duration of fecal incontinence, pudendal nerve damage, patient age, symptom severity, pretreatment anal canal pressures, and results of anal ultrasonography. The presence of some degree of anorectal sensation is the only preoperative assessment that has been found to be predictive of response to surgical therapy. It is recommended that outcome measures for fecal incontinence be more clearly defined, that future biofeedback studies elaborate the predictive value of pretreatment anorectal sensation and the response to sensory retraining, and that postsurgical measurements such as anal squeeze pressure and sphincter length be taken into account.

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Fecal incontinence is an underreported problem in the general population; it is especially common in elderly persons (aged >or=65 years) residing in the community or in long-term care settings. It affects more women than men during younger years, but this differential narrows with age. Physiological changes such as sphincter muscle and sensory abnormalities in the anorectal region contribute to this problem, as do factors such as dementia, physical disability, and fecal impaction. Treatment with biofeedback is feasible in many elderly patients. Those with advanced dementia or physical disability may benefit from a bowel habit training program. Selected patients may require surgical sphincter repair. Minimally invasive techniques such as radiofrequency energy application offer promising future treatment options. The purpose of this review is to provide current information on fecal incontinence and its management in the elderly.

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Statistics abound demonstrating the aging of the population, and this comes as no news to physicians caring for an increasing number of elderly patients. This group experiences the expected age-related physiologic declines, including systems critical to integrative functions such as immunologic, neurologic, and metabolic systems. Although an increased prevalence of several common gastrointestinal disorders occurs in the elderly person, aging per se appears to have less direct effect on most gastrointestinal functions, in large part because of the functional reserve of the gastrointestinal tract. Although irritable bowel symptoms decrease with aging, there seems to be an increase in many gastrointestinal disorders of function and motility. The gastroenterologist will frequently encounter elderly patients with complaints of dysphagia, anorexia, dyspepsia, and disorders of colonic function. Understanding age-related changes in gastrointestinal physiology and effects of common comorbid illnesses enhances the ability to evaluate and treat these common, troublesome symptoms.

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