Extent of eosinophilic esophagitis predicts response to treatment.

Background and study aim The clinical impact of eosinophilic esophagitis (EoE) limited to the distal esophagus (Lim-EE) vs. diffuse involvement (Dif-EE) is unknown. This study compared clinical characteristics and outcomes of Lim-EE vs. Dif-EE. Patients and methods This retrospective, single-center study of patients with EoE between December 2011 and December 2019 evaluated treatment response based on repeated pathology and/or clinical improvement using comparative statistics. Results 479 patients were identified (126 Lim-EE, 353 Dif-EE). Lim-EE patients had a higher incidence of endoscopically identified esophagitis (23.0 % vs. 14.7 %; P  = 0.04), were older (50.8 [SD 16.2] vs. 46.4 [SD 15.3] years; P  = 0.007), and were more likely to present with iron deficiency anemia (5.6 % vs. 1.7 %; P  = 0.05), dyspepsia (15.1 % vs. 8.8 %; P  = 0.06) or for Barrett's surveillance (10.3 % vs. 3.7 %; P  = 0.02). Patients with Dif-EE presented more frequently with dysphagia (57.2 % vs. 45.2 %; P  = 0.02). Both groups had similar proton pump inhibitor (87.2 % vs. 83.3 %; P  = 0.37) and steroid (12.8 % vs. 21.4 %; P  = 0.14) use. Patients with Lim-EE had a better clinicopathologic response (61.5 % vs. 44.8 %; P  = 0.009). On multivariate analysis, EoE extent predicted treatment response with an odds ratio of 1.89 (95 % confidence interval 1.13-3.20; P  = 0.02). However, treatment response based only on repeat biopsy results showed no statistical difference between Lim-EE (52.5 %) and Dif-EE (39.7 %; P  = 0.15). Conclusions Lim-EE may represent a distinct phenotype separate from Dif-EE, with more overlap with gastroesophageal reflux disease and better treatment response.

Medication use and polypharmacy in patients referred to a tertiary gastroenterology practice.

Introduction. Commonly prescribed medications are associated with various gastrointestinal (GI) side effects but few data are available on prescription medication use and polypharmacy in a gastroenterology outpatient practice. We aimed to examine the prevalence of polypharmacy, defined as the simultaneous use of 5 or more medications.Methods. A descriptive correlational study of consecutive outpatient consultations in 988 patients referred to a tertiary gastroenterology practice. Main outcome measurements were frequency of prescription medication use and polypharmacy.Results. The most common GI symptoms were abdominal pain (72%), nausea (57%), and constipation (53%). The frequency of polypharmacy was 10%. Eighty percent of patients took at least one medication and 60% took two or more. The most frequently used medication classes were proton pump inhibitors (43%), followed by benzodiazepines (30%), selective serotonin-reuptake or norepinephrine-reuptake inhibitors (28%), non-steroidal anti-inflammatory drugs (27%), and opioids (21%).Conclusion. There was a higher use of prescription medicine including antidepressants, and a lower frequency of polypharmacy in our study cohort compared to the general population. The use of medications may have contributed to the symptoms leading to our study's population GI consultation.

Creation of a score to predict risk of high conscious sedation requirements in patients undergoing endoscopy.

BACKGROUND AND AIMS: The administration of intravenous conscious sedation to patients undergoing GI endoscopy carries a risk of cardiopulmonary adverse events. Our study aim was to create a score that stratifies the risk of occurrence of either high-dose conscious sedation requirements or a failed procedure. METHODS: Patients receiving endoscopy via endoscopist-directed conscious sedation were included. The primary outcome was occurrence of sedation failure, which was defined as one of the following: (1) high-dose sedation, (2) the need for benzodiazepine/narcotic reversal agents, (3) nurse-documented poor patient tolerance to the procedure, or (4) aborted procedure. High-dose sedation was defined as >10 mg of midazolam and/or >200 µg of fentanyl or the meperidine equivalent. Patients with sedation failure (n = 488) were matched to controls (n = 976) without a sedation failure by endoscopist and endoscopy date. RESULTS: Significant associations with sedation failure were identified for age, sex, nonclonazepam benzodiazepine use, opioid use, and procedure type (EGD, colonoscopy, or both). Based on these 5 variables, we created the high conscious sedation requirements (HCSR) score, which predicted the risk of sedation failure with an area under the curve of 0.70. Compared with the patients with a risk score of 0, risk of a sedation failure was highest for patients with a score ≥3.5 (odds ratio, 17.31; P = 2 × 10-14). Estimated area under the curve of the HCSR score was 0.68 (95% confidence interval, 0.63-0.72) in a validation series of 250 cases and 250 controls. CONCLUSIONS: The HCSR risk score, based on 5 key patient and procedure characteristics, can function as a useful tool for physicians when discussing sedation options with patients before endoscopy.

Prophylactic Snare Tip Soft Coagulation and Its Impact on Adenoma Recurrence After Colonic Endoscopic Mucosal Resection.

BACKGROUND: Up to 20% of patients can have recurrence of adenomatous tissue at first surveillance study after colon endoscopic mucosal resection of large polyps. AIMS: To determine whether an educational intervention discussing thermal ablation of lateral margins of the mucosectomy site of post-endoscopic mucosal resection defect with snare tip soft coagulation (STSC) would decrease adenoma recurrence. METHODS: We performed a single-center quality improvement project from November 1, 2016, to November 30, 2017. Gastroenterologists underwent an educational intervention demonstrating the treatment of peripheral margins of mucosectomy site with STSC after standard mucosectomy technique. These cases (intervention group) were compared with consecutive procedures performed prior to commencement of the quality improvement study (pre-intervention group). Patients with large colorectal lesions (≥ 20 mm) were included. RESULTS: Of the 120 patients here included, overall demographics of the groups were similar and the most common histology was sessile serrated adenoma (study group 45% vs 32% control group). Adenoma recurrence on intervention group and pre-intervention group was 12% versus 30%; p = 0.01. On univariate analysis, biopsy prior to mucosectomy, intraprocedural bleeding, and application of STSC on mucosectomy defect were the strongest predictors of adenoma recurrence. Adenoma recurrence in the intervention group was significantly lower than in the pre-intervention group in both univariate (odds ratio, 0.3 [95% CI, 0.11-0.80]) and multivariate analyses (odds ratio, 0.2 [95% CI, 0.12-0.92]). CONCLUSIONS: The implementation of STSC of post-endoscopic mucosal resection peripheral defects is clinically feasible and significantly decreased adenoma recurrence.

Endoscopic scar assessment after colorectal endoscopic mucosal resection scars: when is biopsy necessary (EMR Scar Assessment Project for Endoscope (ESCAPE) trial).

OBJECTIVE: It is unclear whether endoscopic assessment of scars after colorectal endoscopic mucosal resection (EMR) has to include biopsies, even if endoscopy is negative. Vice versa, endoscopic diagnosis of recurrent adenoma may not require biopsy before endoscopic reinterventions. We prospectively analysed various endoscopic modalities in the diagnosis of recurrence following EMR. DESIGN: We conducted a prospective study of patients undergoing colonoscopy after EMR of large (≥20 mm) colorectal neoplasia. Endoscopists predicted recurrence and confidence level with four imaging modes: high-definition white light (WL) and narrow-band imaging (NBI) with and without near focus (NF). Separately, 26 experienced endoscopists assessed offline images. RESULTS: Two hundred and thirty patients with 255 EMR scars were included. The prevalence of recurrent adenoma was 24%. Diagnostic values were high for all modes (negative predictive value (NPV) ≥97%, positive predictive value (PPV) ≥81%, sensitivity ≥90%, specificity ≥93% and accuracy ≥93%). In high-confidence cases, NBI with NF had NPV of 100% (95% CI 98% to 100%) and sensitivity of 100% (95% CI 93% to 100%). Use of clips at initial EMR increased diagnostic inaccuracy (adjusted OR=1.68(95% CI 1.01 to 2.75)). In offline assessment, specificity was high for all imaging modes (mean: ≥93% (range: 55%-100%)), while sensitivity was significantly higher for NBI-NF (82%(72%-93%)%)) compared with WL (69%(38%-86%); p<0.001), WL-NF (68%(55%-83%); p<0.001) and NBI (71%(59%-90%); p<0.001). CONCLUSION: Our study demonstrates very high sensitivity and accuracy for all four imaging modalities, especially NBI with NF, for diagnosis of recurrent neoplasia after EMR. Our data strongly suggest that in cases of high confidence negative optical diagnosis based on NBI-NF, no biopsy is needed to confirm absence of recurrence during colorectal EMR follow-up. A high confidence positive optical diagnosis can lead to immediate resection of any suspicious area. In all cases of low confidence, biopsy is still required. TRIAL REGISTRATION NUMBER: NCT02668198.

Adenoma recurrence after endoscopic mucosal resection: propensity score analysis of old and new colonoscopes and Sydney recurrence tool implementation.

BACKGROUND AND STUDY AIMS: Risk factors for colorectal adenoma recurrence after endoscopic mucosal resection (EMR) have been well documented. We assessed the efficacy of the newer 190 colonoscope versus the standard 180 colonoscope for complete resection of lateral spreading lesions. PATIENTS AND METHODS: A single-center, retrospective study of patients who underwent EMR with Olympus 180 or 190 colonoscopes from January 1, 2010 to September 30, 2016. We included patients with lesions ≥ 20 mm and surveillance colonoscopy (SC1) after index EMR. A propensity score approach with inverse probability weighting was used to control for potential confounders. A secondary aim was to identify risk factors for recurrence and assess the applicability of the Sydney EMR recurrence tool (SERT) by grading each lesion of our cohort and analyzing associations with recurrence. RESULTS: Two hundred ninety-one lesions met inclusion criteria for the study. Odds ratio (OR) for recurrence with the 190 colonoscope was 1.06 ( P  = .85). Adenoma size ( P  = .02) and use of argon plasma coagulation (APC; P  < .001) were risk factors for recurrence. Lesions with SERT scores > 0 had a higher recurrence risk during follow-up (32 % vs 21 %; OR 1.71; P  = .05). Lesions with SERT scores = 0 reached a plateau for recurrence at 12 and 18 months in Kaplan-Meier curves. CONCLUSIONS: The use of 190 colonoscopes did not measurably affect adenoma recurrence at SC1. Recurrence was associated with adenoma size, complementary APC for resection, and SERT scores > 0. Lesions with SERT scores = 0 that remain negative for recurrence at 18 months may return to routine surveillance.

Polymorphisms of 5-HTT LPR and GNß3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial.

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.

Epidemiology and management of chronic constipation in elderly patients.

Constipation is a common functional gastrointestinal disorder, with prevalence in the general population of approximately 20%. In the elderly population the incidence of constipation is higher compared to the younger population, with elderly females suffering more often from severe constipation. Treatment options for chronic constipation (CC) include stool softeners, fiber supplements, osmotic and stimulant laxatives, and the secretagogues lubiprostone and linaclotide. Understanding the underlying etiology of CC is necessary to determine the most appropriate therapeutic option. Therefore, it is important to distinguish from pelvic floor dysfunction (PFD), slow and normal transit constipation. Evaluation of a patient with CC includes basic blood work, rectal examination, and appropriate testing to evaluate for PFD and slow transit constipation when indicated. Pelvic floor rehabilitation or biofeedback is the treatment of choice for PFD, and its efficacy has been proven in clinical trials. Surgery is rarely indicated in CC and can only be considered in cases of slow transit constipation when PFD has been properly excluded. Other treatment options such as sacral nerve stimulation seem to be helpful in patients with urinary dysfunction. Botulinum toxin injection for PFD cannot be recommended at this time with the available evidence. CC in the elderly is common, and it has a significant impact on quality of life and the use of health care resources. In the elderly, it is imperative to identify the etiology of CC, and treatment should be based on the patient's overall clinical status and capabilities.

Relamorelin Relieves Constipation and Accelerates Colonic Transit in a Phase 2, Placebo-Controlled, Randomized Trial.

BACKGROUND & AIMS: Ghrelin receptors are located in the colon. Relamorelin is a pentapeptide selective agonist of ghrelin receptor 1a with gastric effects, but its effects in the colon are not known. We aimed to evaluate the effects of relamorelin on bowel movements (BMs) and gastrointestinal and colonic transit (CT) in patients with chronic constipation. METHODS: We performed a study of 48 female patients with chronic constipation who fulfilled the Rome III criteria and had 4 or fewer spontaneous BMs (SBMs)/wk. In a randomized (1:1), double-blind, parallel-group, placebo-controlled trial, the effects of relamorelin (100 µg/d, given subcutaneously) were tested during 14 days after a 14-day baseline, single-blind phase in which patients were given placebo at 2 Mayo Clinic sites. The participants' mean age was 40.6 ± 1.5 y, with a mean body mass index of 25.7 ± 0.6 kg/m(2), with 1.7 ± 0.1 SBM/wk, and a mean stool consistency of 1.2 ± 0.1 on the Bristol scale during this baseline period. The effect of treatment on transit was measured in 24 participants with colonic transit of less than 2.4 (geometric center at 24 h) during the baseline period. Gastric emptying, small-bowel transit, and CT were measured during the last 2 days that patients received relamorelin or placebo. Bowel function was determined from daily diaries kept by patients from days 1 through 28. Study end points were time to first BM, SBMs/wk, complete SBMs/wk, stool form, and ease of stool passage. Effects of relamorelin were assessed by analysis of covariance. RESULTS: Compared with placebo, relamorelin accelerated gastric emptying half-time (P = .027), small-bowel transit (P = .051), and CT at 32 hours (P = .040) and 48 hours (P = .017). Relamorelin increased the number of SBMs (P < .001) and accelerated the time to first BM after the first dose was given (P = .004) compared with placebo, but did not affect stool form. Adverse events associated with relamorelin included increased appetite, fatigue, and headache. CONCLUSIONS: Relamorelin acts in the colon to significantly reduce symptoms of constipation and accelerate CT in patients with chronic constipation, compared with placebo. ClinicalTrial.Gov registration number: NCT01781104.

Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

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.

Accuracy of in vivo colorectal polyp discrimination by using dual-focus high-definition narrow-band imaging colonoscopy.

BACKGROUND: Discriminating neoplastic from non-neoplastic polyps can significantly reduce the cost of colonoscopy. The American Society for Gastrointestinal Endoscopy (ASGE) recently set threshold levels for optical diagnostic accuracy to be acceptable for clinical use. OBJECTIVE: In this study, we compare a novel colonoscope capable of dual-focus imaging with standard colonoscopy with respect to the ASGE guidelines. SETTING: An academic medical center ambulatory surgical center. PATIENTS AND INTERVENTIONS: Patients at average risk were randomized to standard colonoscopy (Olympus CF-H180 and Exera II 180 colonoscopes, Olympus America, Center Valley, Pa) or dual-focus colonoscopy (Olympus CF-HQ190 and Exera III 190 colonoscopes, Olympus America). All polyps were given an optical diagnosis and compared with histology. RESULTS: A total of 600 patients were consented and 522 completed all aspects of the procedure. A total of 927 polyps were analyzed. Optical diagnostic accuracy was 79% (95% confidence interval, 74%-83%) for the 190 and 77% (95% confidence interval, 73%-81%) for the 180 colonoscope. Adenoma detection rates were also similar between the 2 groups (50% for the 190 vs 52% for the 180 colonoscope). For small distal rectosigmoid polyps with a high confidence diagnosis, the negative predictive value for adenoma was 96% (range 89%-99%) for the 180 in the narrow-band imaging (NBI) mode and 97% (range 88%-99%) for the 190 colonoscope in NBI mode. Agreement of surveillance intervals by using optical diagnosis was 94% to 95% for all modalities (180 and 190 colonoscopes, white light imaging, NBI). LIMITATIONS: Our study evaluated the accuracy of the 180 and 190 colonoscopes at a center with already-established expertise in endoscopic imaging. CONCLUSIONS: Both traditional and new dual-focus colonoscopes provide highly accurate optical polyp discrimination. There was no difference between the 2 systems in terms of discrimination or adenoma detection. Both systems are consistent with ASGE guidelines for optical diagnosis of selected colorectal polyps without histological confirmation.

Colonic endoscopic mucosal resection of large polyps: Is it safe in the very elderly?

BACKGROUND: Outcomes on colon endoscopic mucosal resection in the very elderly patient population are unknown. AIMS: Aims of this study were to evaluate the outcomes and safety of colon endoscopic mucosal resection in this target population. METHODS: Observational, retrospective study of patients ≥ 80 years of age that underwent colon endoscopic mucosal resection ≥ 2 cm. Demographics, American Society of Anesthesiologists classification, procedural data, and surgical treatment data were collected. RESULTS: One-hundred-and-thirty-one colon endoscopic mucosal resections were performed on 99 patients ≥ 80 years of age with a mean age of 84. The majority of American Society of Anesthesiologists class was II. Mean lesion size was 3.3 cm (range, 2-12.5 cm), more procedures were performed in the right colon and adenoma/tubulovillous adenoma was the most common pathology. En bloc resection was performed on 26.7% of polyps (N=35). Eight procedure-related adverse events (8/131, 6.1%) occurred. No anaesthesia related adverse events or deaths occurred. Six patients required a colonic operation, and overall, 94% of the patient cohort evaded a colon operation. CONCLUSIONS: Colon endoscopic mucosal resection in very elderly patients can be performed at experienced endoscopy centres with a low rate of complications and offers these patients a non-surgical option of management of colorectal lesions.

Gastroparesis: from concepts to management.

While the symptoms of gastroparesis are common, an accurate diagnosis is based on a combination of those symptoms with a documented delay in gastric emptying. Typical symptoms include nausea, vomiting, early satiety, postprandial fullness, bloating, and abdominal discomfort. Patients with gastroparesis face many diagnostic and therapeutic challenges. The most common origins of gastroparesis are idiopathic causes and diabetes mellitus. The increased use of certain medications in medicine today, including opiates and drugs with anticholinergic properties, can alter gastrointestinal functions and mimic symptoms of gastroparesis. Accordingly, alternative explanations for symptoms and altered gastrointestinal function need to be considered. Numerous clinical sequelae, including weight loss and severe protein-calorie malnutrition, may be seen in advanced stages of gastroparesis. This article provides an overview of gut sensorimotor function to help the reader better understand the clinical presentation of patients with dyspepsia and those who may have accompanying delayed gastric emptying that meets criteria for gastroparesis. Techniques available for diagnosing motor dysfunction and the principles of gastroparesis management are reviewed. Nutrition recommendations and a review of pharmacologic agents, nonpharmacologic techniques, and novel treatment modalities are provided.

Linaclotide, novel therapy for the treatment of chronic idiopathic constipation and constipation-predominant irritable bowel syndrome.

Chronic constipation (CC) and irritable bowel syndrome with constipation (IBS-C) are common gastrointestinal (GI) disorders. Current treatment options, either prescription or nonprescription medications, have limited efficacy in a subset of patients. There is significant demand for more efficacious medications for the treatment of CC and IBS-C. Linaclotide, a secretagogue, has a novel mechanism of action designed to treat patients with CC and IBS-C. It has a low oral bioavailability with negligible systemic side effects, and it acts locally in the intestinal lumen. In several clinical trials, in health and disease, linaclotide has demonstrated durable efficacy and safety in CC and IBS-C. Linaclotide received approval by the Federal Drug Administration in August 2012 to treat chronic idiopathic constipation and IBS-C.

Factors associated with increased bleeding post-endoscopic mucosal resection.

OBJECTIVE: Our aim was to identify patient and procedure characteristics that correlate with increased likelihood of bleeding during and after endoscopic mucosal resection (EMR), and thus anticipate the need for preventative therapy. METHODS: This was a retrospective, observational, descriptive study using a prospective EMR database, performed in a tertiary-care center. A total of 935 EMR of various locations within the gastrointestinal tract were collected. The main outcome measurement was early bleeding (occurring during the procedure) and delayed bleeding (occurring after the completion of the procedure and up to 30 days after). RESULTS: Early bleeding occurred in 5.3% (50/935) of the procedures. In multivariate logistic regression analysis, esophageal EMR (OR 2.5, 95% CI 1.2-5, P = 0.0009) and increase in lesion size (OR 1.24, 95% CI 1.1-1.5, P = 0.003) were both associated with higher odds of early bleeding in EMR when controlling for age, gender and non-steroidal anti-inflammatory drugs (NSAIDs)/clopidogrel use. Delayed bleeding occurred after 3.1% (n = 29) of the procedures. Of these, 86.2% (25/29) required hospital admission and endoscopic intervention to confirm and/or treat bleeding site. In multivariate logistic regression analysis, increased lesion size (OR 1.3, 95% CI 1.1-1.5, P = 0.004) was associated with higher incidence of delayed bleeding post-EMR. CONCLUSIONS: In experienced hands bleeding during and after EMR appears to be uncommon. Larger lesions are at increased risk of early and delayed bleeding.

Functional Dyspepsia Treatment Trial (FDTT): a double-blind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating symptoms, psychopathology, pathophysiology and pharmacogenetics.

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).

Chronic constipation in the elderly.

Chronic constipation is a common problem in the elderly, with a variety of causes, including pelvic floor dysfunction, medication effects, and numerous age-specific conditions. A stepwise diagnostic and therapeutic approach to patients with chronic constipation based on historical and physical examination features is recommended. Prudent use of fiber supplements and laxative agents may be helpful for many patients. Based on their capabilities, patients with pelvic floor dysfunction should be considered for pelvic floor rehabilitation (biofeedback), although efficacy in the elderly is uncertain. Clinical awareness and focused testing to identify the physiologic abnormalities underlying constipation, while being mindful of situations unique to the elderly, facilitate management, and improve patient outcomes.

Prevalence and impact of musculoskeletal injury among endoscopists: a controlled pilot study.

BACKGROUND: Endoscopy-associated musculoskeletal injury has not been well studied. Our aim was to identify the frequency and significance of musculoskeletal injury among gastroenterologists compared with a similar group of nonprocedure-oriented internal medicine specialists and subspecialists. METHODS: An electronic survey was developed and administered to all gastroenterologists and hepatologists [gastroenterologists (GI) group] and a sampling of nonprocedure-oriented internal medicine specialists and subspecialists (non-GI group) employed by Mayo Clinic. The questionnaire assessed several areas including current or past pain injury associated with performing endoscopy, location and description of pain or injury, impact of pain or injury, and prevention strategies. A modified survey was sent to the control group. RESULTS: The response rate was 63% in the GI group and 45% in the non-GI group. The 2 groups were of similar age and level of physical activity. The frequency of musculoskeletal injury was higher in the GI group (74% vs. 35%; P<0.001). The most common sites of injury among the GI group were the thumb (19%), low back (19%), hand (17%), and neck (10%). There was no significant association between volume of endoscopy or years performing endoscopy and injury. Most of the GI group made modifications in their endoscopic practice to reduce injury risk. CONCLUSIONS: Musculoskeletal injury occurs more commonly among gastroenterologists than nonprocedure-oriented internal medicine specialists. Most reported minor injuries, but members of the GI group tended to have more severe repercussions relating to ability to work. More attention to injury prevention is needed among gastroenterologists.

Effects of amitriptyline on gastric sensorimotor function and postprandial symptoms in healthy individuals: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Low-dose tricyclic antidepressants have been used to treat chronic somatic and gastrointestinal pain disorders, including refractory functional dyspepsia. However, there are only limited data on the effects of these drugs on upper gastrointestinal function. AIM: To compare the effects of two doses of amitriptyline (AMT) and placebo on gastric accommodation, emptying, satiation, and postprandial symptoms in healthy volunteers. METHODS: Using a parallel-group, double-blind, placebo-controlled design, 41 healthy volunteers were randomized to AMT 25 mg, AMT 50 mg, or placebo for 2 wk. During the final 3 days of therapy, the following end points were assessed: fasting and postprandial gastric volumes, 2- and 4-h gastric emptying, time and volume to maximum satiation using a nutrient drink test, and postprandial symptoms 30 min later using 10-cm visual analog scales. AMT and metabolite levels were measured. RESULTS: AMT slowed gastric emptying at 2 h (median 75% for placebo, 57% for AMT 25 mg, 67% for AMT 50 mg; P= 0.037) and 4 h (median 98% for placebo, 96% for AMT 25 mg, 92% for AMT 50 mg; P= 0.003). AMT did not affect gastric volumes or satiation volume, but it did reduce nausea scores at 30 min in a dose-dependent manner (median 2.1 for placebo, 0.9 for AMT 25 mg, and 0.0 for AMT 50 mg; P= 0.009). CONCLUSION: In healthy volunteers, AMT slows gastric emptying of solids, but it does not significantly affect gastric volumes or satiation. AMT reduces nausea after challenge with a high calorie liquid load.

Prospective, controlled tandem endoscopy study of narrow band imaging for dysplasia detection in Barrett's Esophagus.

BACKGROUND & AIMS: High-resolution endoscopy with narrow band imaging (NBI) enhances the visualization of mucosal glandular and vascular structures. This study assessed whether narrow band targeted biopsies could detect advanced dysplasia using fewer biopsy samples compared with standard resolution endoscopy. METHODS: We conducted a prospective, blinded, tandem endoscopy study in a tertiary care center with 65 patients with Barrett's esophagus undergoing evaluation for previously detected dysplasia. Standard resolution endoscopy was used first to detect visible lesions. Narrow band endoscopy was then used by another gastroenterologist to detect and biopsy areas suspicious for dysplasia. The lesions initially detected by standard resolution endoscopy were then disclosed and biopsied, after biopsy of the lesions targeted with NBI. Finally, random 4-quadrant biopsies were taken throughout the segment of Barrett's mucosa. RESULTS: Higher grades of dysplasia were found by NBI in 12 patients (18%), compared with no cases (0%) in whom standard resolution white light endoscopy with random biopsy detected a higher grade of histology (P < .001). Correspondingly, narrow band directed biopsies detected dysplasia in more patients (n = 37; 57%) compared with biopsies taken using standard resolution endoscopy (n = 28; 43%). In addition, more biopsies were taken using standard resolution endoscopy with random biopsy compared with narrow band targeted biopsies (mean 8.5 versus 4.7; P < .001). CONCLUSIONS: In patients evaluated for Barrett's esophagus with dysplasia, NBI detected significantly more patients with dysplasia and higher grades of dysplasia with fewer biopsy samples compared with standard resolution endoscopy.