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Background Bacterial translocation plays a pivotal role in the natural course of cirrhosis and its complications. Serum-derived bovine immunoglobulin (SBI) is an oral medical food that has been shown to both reduce inflammation in the intestines and neutralize bacteria. It represents a unique intervention that has not been studied in this population. Methodology We conducted a prospective open-label trial with an eight-week treatment phase of SBI. Individuals were assessed using lactulose breath testing, serum markers for enterocyte damage and bacterial translocation, and the Chronic Liver Disease Questionnaire (CLDQ) prior to and after completion of the treatment phase. Results We evaluated nine patients with a diagnosis of decompensated cirrhosis with ascites. Subjects had a mean Model for End-Stage Liver Disease (MELD) score of 11.6 ± 3.0 and were not taking lactulose or antibiotics. All subjects tolerated SBI well with no significant adverse events or changes to any of the six domains of the CLDQ. Laboratory tests including liver tests and MELD score remained stable over the course of treatment. There were no significant changes in the rates of small intestinal bacterial overgrowth (55.6% vs 55.6%, p = 1.00) or serum levels of lipopolysaccharide-binding protein, intestinal fatty acid-binding protein, or soluble CD14 (p-values 0.883, 0.765, and 0.748, respectively) when comparing values prior to and immediately after treatment. Conclusions No adverse events or significant changes to the quality of life were detected while on treatment. There were no statistically significant differences in our outcomes when comparing individuals before and after treatment in this small prospective proof-of-concept pilot study. Further prospective randomized studies could be beneficial.

Cholestatic hepatitis has not been reported as a paraneoplastic syndrome of endometrial adenocarcinoma to our knowledge. We present a patient who, shortly after endometrial adenocarcinoma diagnosis, presented with elevated liver chemistries in the setting of an acute, paraneoplastic sensorimotor polyneuropathy. Infectious, autoimmune, pharmacologic, malignant, metabolic, and structural causes of cholestatic hepatitis were screened for and ruled out. Our patient was diagnosed with simultaneous cholestatic hepatitis and acute sensorimotor polyneuropathy as possible paraneoplastic syndromes of endometrial adenocarcinoma. Clinicians should include paraneoplastic processes of cancer in the differential diagnosis for liver injury, especially when workup for alternative causes is unrevealing.

Primary mucinous adenocarcinoma of the appendix is a rare gastrointestinal malignancy. Fistulous tract formation is a complication that is cited in literature. An 85-year-old man with multiple comorbidities presented with several weeks of persistent non-bloody diarrhea. Laboratory work-up was non-diagnostic. Abdominal imaging with barium contrast showed an enterocolonic fistulous tract extending from the duodenum to the cecum involving an enlarged appendiceal mass. Subsequent biopsy confirmed mucinous appendiceal neoplasm with peritoneal spread to the liver and mesentery. This is the first report describing an enterocolonic fistula formation resulting from this malignancy.

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. GNβ3 825CT 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 GNβ3 825CT and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy.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 GNβ3 825CT and 5-HTT LPR was performed utilizing PCR-based methods.GNβ3 825CT 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 GNβ3 825CT 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).GNβ3 825CT and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.

SummaryBackground Functional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89–90%), postprandial fullness (75–88%), and early satiety (50–82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non-specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive. Aim To present current management options for the treatment of FD (therapeutic gain/response rate noted when available). Results The utility of Helicobacter pylori eradication for the treatment of FD is modest (6–14% therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI) (7–10% therapeutic gain), histamine-type-2-receptor antagonists (8–35% therapeutic gain), prokinetic agents (18–45%), tricyclic antidepressants (TCA) (response rates of 64–70%), serotonin reuptake inhibitors (no better than placebo) is limited and hampered by inadequate data. This review discusses dietary interventions and analyses studies involving complementary and alternative medications, and psychological therapies. Conclusions A reasonable treatment approach based on current evidence is to initiate therapy with a daily PPI in H. pylori-negative FD patients. If symptoms persist, a therapeutic trial with a tricyclic antidepressant may be initiated. If symptoms continue, the clinician can possibly initiate therapy with an anti-nociceptive agent, a prokinetic agent, or some form of complementary and alternative medications, although evidence from prospective studies to support this approach is limited.

Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease. The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux. Guidelines for esophageal reflux testing are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Issues regarding the utilization of conventional, catheter-based pH monitoring are discussed. Improvements in the interpretation of esophageal pH recordings through the use of symptom-reflux association analyses as well as limitations gleaned from recent studies are reviewed. The clinical utility of pH recordings in the proximal esophagus and stomach is examined. Newly introduced techniques of duodenogastroesophageal reflux, wireless pH capsule monitoring and esophageal impedance testing are assessed and put into the context of traditional methodology. Finally, recommendations on the clinical applications of esophageal reflux testing are presented.

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.

This clinical review on the treatment of patients with gastroparesis is a consensus document developed by the American Motility Society Task Force on Gastroparesis. It is a multidisciplinary effort with input from gastroenterologists and other specialists who are involved in the care of patients with gastroparesis. To provide practical guidelines for treatment, this document covers results of published research studies in the literature and areas developed by consensus agreement where clinical research trials remain lacking in the field of gastroparesis.

An abnormality in transit is commonly considered to account for unexplained gastrointestinal (GI) symptoms. Since the symptoms of delayed transit overlap with those of accelerated transit, direct measurement of GI transit is needed to establish an accurate diagnosis. Similarly, since symptoms originating from one part of the gut may overlap with symptoms from another, localizing transit abnormality to one organ vs. another using direct measurement is an important part of diagnostic evaluations. Consequently, noninvasive tests of GI transit should be done early in the evaluation to guide therapy. We now have tools to measure transit accurately; results of transit tests often depend on the conditions selected for the test, so test results will match clinical expectations most closely when test conditions are selected to reproduce the circumstances for symptom production. This review describes the most commonly used methods for the measurement of GI transit including the gastric emptying test for some dyspeptic symptoms, small bowel transit test for dyspeptic symptoms and diarrhea, colonic transit test for constipation, and factors that influence the result of these studies. As we make progress in our understanding of the pathophysiology of transit disorders, the clinical usefulness of these diagnostic tests will be further enhanced.

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.

OBJECTIVES: The aim of this study was to describe the clinical, manometric, and serological characteristics of 12 patients with paraneoplastic GI motor dysfunction and to assess the contributory role of diagnostic tests. METHODS: Twelve patients diagnosed with malignant tumors and GI motor dysfunction were identified at the Mayo Clinic from 1985 to 1996. RESULTS: Cancers identified were: nine small cell lung carcinoma (SCLC), one anaplastic lung adenocarcinoma, one retroperitoneal lymphoma, and one ovarian papillary serous adenocarcinoma. GI symptoms preceded the tumor diagnosis in all cases of SCLC (mean, −8.7 months, range, −1 to −24 months, n = 9). The diagnosis of a malignant tumor preceded the onset of GI symptoms in the three patients with other neoplasms (6, 12, and 24 months). Five of the nine patients found to have SCLC had no evidence of tumor on initial chest x-ray. One or more paraneoplastic autoantibodies were found in 10 of the 11 patients tested by autoimmune serology. Type 1 antineuronal nuclear antibody (ANNA-1 or anti-Hu) was detected in eight of the nine patients with SCLC (one patient was not tested). The patient with ovarian carcinoma had type 1 Purkinje cell cytoplasmic antibody (PCA-1 or anti-Yo). N-type calcium channel antibodies were found in one patient with SCLC, one with a retroperitoneal B cell lymphoma, and one with ovarian carcinoma. Gastric emptying was delayed in 89% (eight of nine tested) and 80% (four of five tested) had esophageal dysmotility. Autonomic reflex tests were abnormal in the seven patients tested. CONCLUSIONS: The diagnosis of paraneoplastic GI motor dysfunction requires a high index of clinical suspicion. A panel of serological tests for paraneoplastic autoantibodies, scintigraphic gastric emptying, and esophageal manometry are useful as first-line screening tests. Seropositivity for ANNA-1, PCA-1, or N-type calcium channel-binding antibodies should prompt further evaluation for an underlying malignancy even when routine imaging studies are negative.

The aim of this study was to evaluate results of completion gastrectomy for severe postgastrectomy gastric stasis. A total of 51 women and 11 men underwent completion gastrectomy for gastric stasis between 1985 and 1996; follow-up was complete in 98% at 5.4 +/- 5 years. All patients had modified Visick scores preoperatively of grade III (37%) or IV (63%). Presentation included combinations of nausea, vomiting, postprandial pain, chronic abdominal pain, and chronic narcotic use. All had undergone prior vagotomy and had a median of four previous gastric operations. Hospital mortality was zero. Complications occurred in 25 patients (40%) and included the following: narcotic withdrawal syndrome (18%), ileus (10%), wound infection (5%), intestinal obstruction (2%), and anastomotic leak (5%). All or most symptoms were relieved in 43% (Visick grade I or II), but 57% of the patients remained in Visick grade III or IV. Nausea, vomiting, and postprandial pain were reduced from 93% to 50%, 79% to 30%, and 58% to 30%, respectively (P

Effects of an irritable bowel syndrome educational class on health-promoting behaviors and symptoms

Our aims were to measure antral axial forces in patients with suspected upper gut dysmotilities and to compare the number of antral contractions detected by an axial force catheter and by manometric sensors in the distal antrum and pylorus. Fifteen patients (2 men, 13 women; mean age 42 years) underwent studies for 3 hr fasting, 2 hr postprandially, and up to 60 min after intravenous erythromycin (3mg/kg). Seven patients had gastroparesis or chronic intestinal pseudoobstruction, five functional disease, and three subacute obstruction. Postprandially, the number of peaks detected by the two methods was not significantly different; however, after erythromycin, the axial catheter detected more contractions (P = 0.02). Erythromycin significantly increased the number of postprandial axial forces (from 1.2 +/- 0.3/min to 2.5 +/- 0.3/min, Por = 0.01) in the whole group and in the organic dysmotility group (P = 0.01). Erythromycin significantly increases the number of axial forces in functional and organic upper gut dysmotilities, but the axial force catheter is not advantageous over manometry for postprandial measurements of antral motility.

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.

The propulsive forces involved in gastric emptying of solid and liquid chyme are incompletely characterized, and the contribution of the proximal region of the stomach to overall propulsion has not been quantifiable. We have used an axial force catheter to characterize longitudinally directed forces during gastric emptying in man. The topography of these forces has been described relative to circumferential contractions, and the contribution of axial forces in experimental models of dumping and gastric stasis were quantified by assessing the effects of intravenous erythromycin and intraduodenal lipid, respectively. There is an excellent correlation between axial forces and gastric emptying of solids in health and in models of gastric dysmotility, suggesting that the axial force catheter semiquantitatively measures propulsive forces during emptying of the human stomach.

The aim of this study was to assess the relationship between altered axial forces and gastric emptying of solids by experimentally inhibiting or stimulating gastric axial forces by intraduodenal lipid or intravenous erythromycin, respectively. In 15 healthy volunteers, we simultaneously measured gastric emptying of solids by scintigraphy, gastroduodenal motility by manometry, and forces along the longitudinal axis of the distal stomach by an axial force transducer. When 25% of the radiolabel had emptied from the stomach, subjects (n = 5 in each group) received normal saline (controls), intraduodenal lipid, or intravenous erythromycin. The test period consisted of the infusion period (10 min) and the subsequent 30 min. Lipid significantly reduced and erythromycin increased axial forces compared with control (lipid: median 0.6 N [0-1.4 interquartile range (IQR)]; erythromycin: median 18.2 N (16.5-20.5 IQR); control: median 4.7 N (3.9-5.2 IQR); P < 0.01). Similarly, antral phasic pressure activities were different relative to control. Gastric axial forces correlated significantly with gastric emptying (Spearman rank correlation = 0.86; P < 0.01). These data are consistent with the hypothesis that axial forces affect gastric emptying of solids and suggest that measurement of axial forces provides an assessment of overall gastric propulsion during the emptying of solids.

Our aim was to measure axial forces in the stomach and to evaluate their relation to circumferential contractions of the gastric walls and the emptying of gastric content. We used a combination of simultaneous radioscintigraphy, gastroduodenal manometry, and an axial force transducer with an inflatable 2-ml balloon fluoroscopically placed in the antrum. In vitro studies demonstrated that the axial force transducer records only antegrade forces along the longitudinal axis of this probe in an intensity-dependent manner. In vivo studies were performed in five healthy subjects for at least 3 h after ingestion of radiolabeled meals. When administered separately, the emptying of liquids or solids from the stomach is associated with generation of antral axial forces and coincident phasic pressure activity; however, almost 20% (average) of gastric axial forces during emptying of liquids or solids are unassociated with proximal or distal antral pressure activity ("isolated" forces). High amplitude antral axial forces and pressures occur during both lag and postlag emptying phases. During emptying of liquids, there is a trend for axial forces to be coincident more often with proximal than with distal antral pressure activity and vice versa for the emptying of solids (P = 0.015). These data suggest that when placed in the antrum, the transducer can semiquantitatively record axial forces during gastric emptying. By combining these observations with the data from in vitro studies, it appears that axial forces predominantly result from traction on the balloon by the longitudinal vector resulting from circumferential gastric contractions. The combination of radioscintigraphy and measurement of antral axial forces is a promising method to evaluate mechanical forces involved in the emptying of the human stomach.

Tests of gastric, small intestinal and colonic motor function provide relevant physiological information and are useful for diagnosing and guiding the management of dysmotilities. Intraluminal pressure measurements may include concurrent measurements of transit or intraluminal pH. A consensus statement was developed and based on reports in the literature, experience of the authors, and discussions conducted under the auspices of the American Neurogastroenterology and Motility Society in 2008. The article reviews the indications, methods, performance characteristics, and clinical utility of intraluminal measurements of pressure activity and tone in the stomach, small bowel and colon in humans. Gastric and small bowel motor function can be measured by intraluminal manometry, which may identify patterns suggestive of myopathy, neuropathy, or obstruction. Manometry may be most helpful when it is normal. Combined wireless pressure and pH capsules provide information on the amplitude of contractions as they traverse the stomach and small intestine. In the colon, manometry assesses colonic phasic pressure activity while a barostat assesses tone, compliance, and phasic pressure activity. The utility of colonic pressure measurements by a single sensor in wireless pressure/pH capsules is not established. In children with intractable constipation, colonic phasic pressure measurements can identify patterns suggestive of neuropathy and predict success of antegrade enemas via cecostomy. In adults, these assessments may be used to document severe motor dysfunction (colonic inertia) prior to colectomy. Thus, intraluminal pressure measurements may contribute to the management of patients with disorders of gastrointestinal and colonic motility.

To the Editor: We present a case of primary esophageal invasion by histiocytic sarcoma (HS), which to the best of our knowledge has not been reported in the literature to date.

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.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.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 (P0.05). Class attendance was associated with improvement in Health-Promoting Lifestyle Profile scores (P0.05) but not with change in pain, quality of life, satisfaction, or health care utilization.A onetime, multidisciplinary class for patients with IBS was associated with improvement in symptoms and health-promoting lifestyle behavior.

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.

Background: Serotonin (5-HT) signaling in the small intestine is involved in motor, sensory and secretory pathways. Studies of neuroendocrine cell mapping in functional dyspepsia (FD), characterized by upper gastrointestinal motor and sensory disturbances, are scarce although it has been previously noted that there is no significant difference in numbers of 5HT cells in duodenum in post infectious FD vs. controls1. In patients with irritable bowel syndrome, another functional bowel disorder, a low density of duodenal neuroendocrine cells is also described2. Aim: To examine the content of neuroendocrine cells in the duodenum of subjects with FD, specifically the relative content of serotonin (5-HT) containing cells and to investigate a possible relationship between neuroendocrine cell numbers and FD subtypes. Methods: A random sample of an adult Swedish population (n = 1000) (the Kalixanda study) underwent upper endoscopy and biopsies taken from the duodenal bulb (D1) and the second part of duodenum (D2). From this study 23 subjects with FD were identified, 13 with postprandial distress syndrome (PDS), 10 with epigastric pain syndrome (EPS) and 12 healthy controls. Immunocytochemistry was performed for Chromogranin A (CGA) and 5-HT. Positive cells were quantified per mm2. Results: Cases and controls showed similar demographics. The number of CGA stained cells was significantly lower in FD patients both in D1 (p = 0.01) and D2 (p = 0.04) whereas there was no significant difference in 5-HT content. See figure. When EPS and PDS were studied separately, the number of CGA stained cells was significantly decreased in D1 in patients with EPS (p = 0.03). Conclusions: The number of duodenal neuroendocrine cells is decreased in FD compared with control subjects, but this is not due to a reduction in the number of 5-HT containing cells. It is possible that this reduction reflects reduced cellular densities of other hormones (e.g. somatostatin) which could result in a high secretion of gastric acid, with a change in motility or visceral sensitivity leading to dyspeptic symptoms in these cases. 1. Futagami S et al. Am J Gastroenterol. 2010 ;105:1835-42. 2. El-Salhy M et al. Scand J Gastroenterol. 2010 ;45:1435-9.

The Functional Dyspepsia Treatment Trial (FDTT): 5-HTT LPR and Gnβ3 825C>T Are Not Pharmacogenetic Markers for FD Antidepressant Treatment Response Yuri A. Saito, Ann E. Almazar, Giles R. Locke, Ernest P. Bouras, Colin W. Howden, Brian E. Lacy, John K. DiBaise, Charlene M. Prather, Bincy Abraham, Hashem El-Serag, Paul Moayyedi, Lawrence A. Szarka, Linda M. Herrick, Katherine E. Tilkes, Cathy D. Schleck, Alan R. Zinsmeister, Nicholas J. Talley

Background & Aims: This study evaluated the effects of a partial 5-hydroxytryptamine (5-HT) 4 agonist, tegaserod, on gastric small bowel and colonic transit in constipation-predominant irritable bowel syndrome (IBS). Methods: After a 1 week run-in period, 24 patients with constipation-predominant IBS were randomized to 1 week of tegaserod, 2 mg twice daily, or placebo treatment. Scintigraphic gastric emptying, small bowel transit, and colonic transit were determined before administration of study drug and after 1 week on the medication. Colonic transit was also measured using radiopaque markers and a single radiograph on day 5. Results: Gastric emptying was unaltered by tegaserod. Proximal colonic filling at 6 hours, a measure of orocecal transit, was accelerated by tegaserod (70.4% ± 1.3% [mean ± SEM] vs. placebo, 46.4 ± 1.9; P = 0.015). Proximal colonic emptying half-time and geometric center at 48 hours were also accelerated by tegaserod compared with baseline, but not compared with placebo. Mean colonic transit time was similar in both groups at baseline and after drug administration (tegaserod, 59.5 ± 2.1 hours; placebo, 62.1 ± 2.1 hours). Conclusions: Tegaserod accelerates orocecal transit, tends to accelerate colonic transit, and deserves further study in patients with constipation-predominant IBS. GASTROENTEROLOGY 2000;118:463-468