Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn.

BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).

Once-daily Mesalamine Formulation for Maintenance of Remission in Ulcerative Colitis: A Randomized, Placebo-controlled Clinical Trial.

GOALS: To evaluate the efficacy and safety of mesalamine granules 1.5 g once daily for maintenance of ulcerative colitis (UC) remission. BACKGROUND: Mesalamine is a first-line treatment for induction and maintenance of UC remission. STUDY: A phase 3, randomized, double-blind, placebo-controlled trial of patients with a history of mild to moderate UC, currently in remission, who received mesalamine granules once daily for 6 months. The primary efficacy endpoint was percentage of patients maintaining UC remission at 6 months. RESULTS: A significantly greater percentage of patients receiving mesalamine granules versus placebo were in remission at 6 months (79.9% vs. 66.7%; P=0.03). A greater percentage of patients receiving mesalamine granules maintained a revised Sutherland Disease Activity Index (SDAI)≤2 with no individual component of revised SDAI>1 and rectal bleeding=0 at 6 months (72.0% vs. 58.1%; P=0.04). No significant differences between groups were observed for change from baseline to 6 months for total SDAI score or its components (ie, stool frequency, rectal bleeding, mucosal appearance, physician's rating of disease). Mesalamine granules treatment resulted in a significantly longer remission duration versus placebo (P=0.02) and decreased patients' risk of relapse by 43% (hazard ratio=0.57; 95% confidence interval, 0.35-0.93; P=0.02). Mesalamine granules were well tolerated, and adverse events related to hepatic, renal, and pancreatic function-potential concerns with long-term treatment-occurred at a rate similar to placebo. CONCLUSIONS: Once-daily mesalamine granules are efficacious and safe for the maintenance of UC remission.

Long-Term Benefit of Mesalamine Granules for Patients Who Achieved Corticosteroid-Induced Ulcerative Colitis Remission.

BACKGROUND: Patients with ulcerative colitis (UC) who achieve remission with corticosteroids often relapse after tapering or discontinuation; alternative treatments limiting steroid exposure and UC relapse would be beneficial. It remains uncertain whether patients with corticosteroid-induced remission experience benefit with mesalamine granules (MG), a locally acting aminosalicylate extended-release capsule formulation for maintenance of UC remission in adults. AIMS: Efficacy and safety of MG 1.5 g once daily was evaluated in patients with UC in corticosteroid-induced remission. METHODS: Data from patients with previous corticosteroid use to achieve baseline UC remission were analyzed from two 6-month randomized, double-blind, placebo-controlled trials and a 24-month open-label extension (OLE). Six-month relapse-free rates were assessed using the revised Sutherland Disease Activity Index. UC-related adverse events (AEs) were recorded during the 30 months. RESULTS: Included were 158 steroid-treated patients in UC remission (MG, n = 105; placebo, n = 53) and 74/105 MG-treated patients who continued MG in the OLE. A significantly larger percentage of patients remained relapse-free at 6 months with MG (77.1 %) versus placebo (54.7 %; P = 0.006), with a 55 % reduction in relapse risk (hazard ratio [HR] 0.45; 95 % CI 0.25-0.79). There was a similar (49.2 %) reduction in risk of UC-related AEs at 6 months (HR 0.51; 95 % CI 0.31-0.84; P = 0.009) that was sustained during the OLE. CONCLUSIONS: MG 1.5 g once daily administered for maintenance of corticosteroid-induced remission was associated with low risk of relapse and UC-related AEs. CLINICALTRIALS.GOV: NCT00744016, NCT00767728, and NCT00326209.

Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial.

IMPORTANCE: Clostridium difficile is the most common cause of health care-associated infection in US hospitals. Recurrence occurs in 25% to 30% of patients. OBJECTIVE: To determine the safety, fecal colonization, recurrence rate, and optimal dosing schedule of nontoxigenic C. difficile strain M3 (VP20621; NTCD-M3) for prevention of recurrent C. difficile infection (CDI). DESIGN, SETTING, AND PARTICIPANTS: Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from June 2011 to June 2013 among 173 patients aged 18 years or older who were diagnosed as having CDI (first episode or first recurrence) and had successfully completed treatment with metronidazole, oral vancomycin, or both at 44 study centers in the United States, Canada, and Europe. INTERVENTIONS: Patients were randomly assigned to receive 1 of 4 treatments: oral liquid formulation of NTCD-M3, 10(4) spores/d for 7 days (n = 43), 10(7) spores/d for 7 days (n = 44), or 10(7) spores/d for 14 days (n = 42), or placebo for 14 days (n = 44). MAIN OUTCOMES AND MEASURES: The primary outcome was safety and tolerability of NTCD-M3 within 7 days of treatment. Exploratory secondary outcomes included fecal colonization with NTCD-M3 from end of study drug through week 6 and CDI recurrence from day 1 through week 6. RESULTS: Among 168 patients who started treatment, 157 completed treatment. One or more treatment-emergent adverse events were reported in 78% of patients receiving NTCD-M3 and 86% of patients receiving placebo. Diarrhea and abdominal pain were reported in 46% and 17% of patients receiving NTCD-M3 and 60% and 33% of placebo patients, respectively. Serious treatment-emergent adverse events were reported in 7% of patients receiving placebo and 3% of all patients who received NTCD-M3. Headache was reported in 10% of patients receiving NTCD-M3 and 2% of placebo patients. Fecal colonization occurred in 69% of NTCD-M3 patients: 71% with 10(7) spores/d and 63% with 10(4) spores/d. Recurrence of CDI occurred in 13 (30%) of 43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (odds ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006); the lowest recurrence was in 2 (5%) of 43 patients receiving 10(7) spores/d for 7 days (OR, 0.1; 95% CI, 0.0-0.6; P = .01 vs placebo]). Recurrence occurred in 2 (2%) of 86 patients who were colonized vs 12 (31%) of 39 patients who received NTCD-M3 and were not colonized (OR, 0.01; 95% CI, 0.00-0.05; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with CDI who clinically recovered following treatment with metronidazole or vancomycin, oral administration of spores of NTCD-M3 was well tolerated and appeared to be safe. Nontoxigenic C. difficile strain M3 colonized the gastrointestinal tract and significantly reduced CDI recurrence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01259726.

Appropriateness of fecal immunochemical testing utilization for colorectal cancer screening at an academic center.

Fecal immunochemical testing (FIT) has become the most utilized test for colorectal cancer (CRC) screening. This retrospective quality assurance report analyzed data for 411 patients from one academic center in Central New York who underwent FIT between September 2015 and September 2016. All 67 positive tests and 344 of 952 negative tests were analyzed. Subjects from the FIT-negative "control group" were chosen at random. The mean age was 67 years and the male/female distribution was 391/20, with differences between the FIT-positive and -negative groups. FIT was inappropriately used in 210 (51%) of the 411 patients. The most common reasons for inappropriate FIT use were a documented refusal of colonoscopy (39.60% of inappropriate use), FIT occurring within the recommended surveillance interval from previous colonoscopy (27.98%), and a Charlson Co-Morbidity Index score ≥5 (22.87%). Other reasons were a history of adenoma (9.25%), family history of CRC/high-risk adenoma <60 years of age (5.84%), active/overt gastrointestinal bleed (4.87%), history of CRC (1.46%), and history of inflammatory bowel disease (1.46%). The results of this study show that FIT is being utilized inappropriately about 50% of the time.

Coffee grounds emesis: not just an upper GI bleed.

BACKGROUND: Acute upper gastrointestinal (UGI) bleeding manifests as hematemesis, melena, or hematochezia. Initial management is identical, irrespective of nasogastric (NG) aspirate results. Current practice includes early upper endoscopy. Significantly fewer high-risk bleeding lesions are found on endoscopy in patients with coffee grounds vs. bloody NG aspirates. OBJECTIVE: We present a case series to illustrate that patients with coffee grounds emesis (CGE) often have other unsuspected illnesses that may be overlooked due to preoccupation with the GI bleed. CASE REPORTS: A retrospective chart review of a series of 6 patients presenting with CGE and admitted for upper GI bleeding was performed. All 6 patients were hemodynamically stable at admission. NG lavage showed coffee grounds that cleared easily. None of the patients required blood transfusions during their hospital stay. Endoscopy in 3 of 6 patients failed to find any significant UGI lesions or stigmata of recent bleed. CONCLUSION: Although patients were admitted for UGI bleeding, the more significant associated diagnoses included acute myocardial infarction, urosepsis, small bowel obstruction, bilateral pulmonary emboli, and acute renal failure. Hemodynamically stable patients presenting with coffee grounds NG aspirate and no fall in hemoglobin/hematocrit should be evaluated for other non-GI bleeding-related conditions even as the GI bleed is being managed.

Idiopathic Esophageal Lipomatosis: An Incidental Benign Discovery.

Gastrointestinal (GI) lipomatosis has been reported in the GI medicine literature, but esophageal lipomatosis has never been reported at all. We report the case of an 86-year-old man with multiple medical comorbidities who was admitted to our hospital for community-acquired pneumonia. Computed tomography angiography of his pulmonary arteries ruled out the possibility of pulmonary embolism but showed a 9-mm circumferential wall thickening in the proximal esophagus measuring -172 HU, which is similar in opacity to the adipose tissue. The patient was asymptomatic and without any current or prior symptoms of dysphagia or odynophagia. The barium esophagogram was unremarkable; there were no strictures, masses, or mucosal abnormalities. There was no evidence of esophageal dilatation on either imaging modality. Esophageal lipomatosis is only described in a few case reports in the radiological literature and, to our knowledge, has not been reported in the GI literature at all. It is important to highlight in the GI literature this as a benign entity that does not cause symptoms and typically does not warrant invasive diagnostic or therapeutic interventions.

Postpolypectomy bleeding in patients undergoing colonoscopy on uninterrupted clopidogrel therapy.

BACKGROUND: The risk of postpolypectomy bleeding (PPB) in patients undergoing colonoscopy on uninterrupted clopidogrel therapy has not been established. OBJECTIVE: To assess the PPB rate and outcome and identify risk factors associated with PPB in patients taking clopidogrel. DESIGN: Single-center, retrospective study. Demographics, clinical parameters, polyp characteristics, polypectomy techniques, and postpolypectomy events in the groups were compared by univariate analysis. Stepwise logistic regression analyses identified independent risk factors associated with PPB. SETTING: Veterans Affairs Medical Center. PATIENTS: A total of 142 patients (375 polypectomies) taking clopidogrel (cases) and 1243 patients (3226 polypectomies) not taking clopidogrel (controls). INTERVENTIONS: None. MAIN OUTCOME MEASUREMENTS: Postpolypectomy bleeding, hospitalization, and mortality. RESULTS: The immediate (intraprocedural) bleeding rate was similar in the 2 groups (2.1% vs 2.1%). Delayed (postprocedural) PPB rate was higher in the group taking clopidogrel (3.5% vs 1.0%, P = .02). Delayed bleeding of significance requiring hospitalization and transfusion/intervention was also higher in patients taking clopidogrel (2.1% vs 0.4%, P = .04). The length of hospital stay and interventions for PPB were comparable between the 2 groups. There was no mortality. Concomitant use of clopidogrel and aspirin/other nonsteroidal anti-inflammatory drugs (odds ratio 3.7; 95% CI, 1.6-8.5) and the number of polyps removed (OR 1.3; 95% CI, 1.2-1.4) were the only significant risk factors associated with PPB. Clopidogrel alone was not an independent risk factor for PPB. LIMITATIONS: Retrospective study and small number of patients with PPB. CONCLUSIONS: The PPB rate is significantly higher in patients undergoing polypectomy while taking clopidogrel and concomitant aspirin/nonsteroidal anti-inflammatory drugs; however, the risk is small and the outcome is favorable. Routine cessation of clopidogrel in patients before colonoscopy/polypectomy is not necessary.

Outcome of retinopathy in chronic hepatitis C patients treated with peginterferon and ribavirin.

The purpose of this study is to evaluate the incidence and outcome of retinopathy in chronic hepatitis C patients treated with peginterferon and ribavirin. A total of 74 hepatitis C patients with baseline eye exams and eye exams during therapy were included. Retinopathy was defined as development of cotton wool spots and/or intra-retinal hemorrhage. Demographics, hepatitis C viral characteristics, treatment and laboratory data, and eye exam findings were compared in groups with and without retinopathy. Retinopathy developed in 28 (38%), early in therapy. Pre-treatment eye exams did not predict risk of retinopathy. Therapy was continued in all but one; cotton wool spots resolved in 24 of 26. All nine patients with intra-retinal hemorrhage had resolution. No patient had retinopathy-related visual deterioration. Retinopathy is common with peginterferon therapy, but the outcome is favorable. Cessation of therapy for retinopathy is not warranted. Severe visual disturbances and scotomas deserve further evaluation.

Hunt for the Shunt: An Unusual Case of Late-onset Hydrothorax in a Patient on Peritoneal Dialysis.

Hydrothorax is a rare complication of peritoneal dialysis occurring in about 2% of continuous ambulatory peritoneal dialysis (CAPD) patients. These effusions occur soon after the onset of dialysis and are usually right-sided. We describe an unusual case of late-onset, left-sided, and recurrent effusions in the setting of CAPD. A 67-year-old patient with end-stage renal disease on CAPD for the last three years was admitted to our hospital with acute hypoxic respiratory failure secondary to a left-sided effusion. Although previously asymptomatic, he had three admissions for bilateral (left predominant) effusions in the last year, all of which were found to be transudative on analysis. Therapeutic thoracentesis once again revealed a transudative effusion with an elevated pleural fluid-serum glucose gradient. On this occasion, pleuro-peritoneal scintigraphy with technetium-99m was performed, uncovering a communication between the peritoneal cavity and the left pleural cavity. The peritoneal dialysis was substituted with hemodialysis, and the patient showed an eventual resolution of left-sided effusions within 18 months. Hydrothorax in peritoneal dialysis is due to the transudation of fluid across congenital or acquired pleuro-peritoneal communications. Pleural fluid with protein content less than 3 g/dl, high glucose, and low lactate dehydrogenase (LDH) relative to blood, and the presence of both D and L isomers of lactic acid suggest a transdiaphragmatic leak. Early diagnosis via peritoneal scintigraphy and appropriate management can prevent significant morbidity and mortality.

Unexplained iron deficiency anemia: does Helicobacter pylori have a role to play?

BACKGROUND AND AIM: Testing for Helicobacter pylori (Hp) infection is recommended for work-up of unexplained iron deficiency anemia (IDA), although the evidence supporting this recommendation is scant. The aim of this study was to investigate the association between Hp infection and unexplained iron deficiency (ID) or IDA in the older adult population without significant upper gastrointestinal source of blood loss. METHODS: Retrospective single-center cohort study; 523 out of 1253 consecutive patients who underwent esophagogastroduodenoscopy with no significant upper and/or lower gastrointestinal source for blood loss or risk factors for IDA. Comparisons were made between the Hp-positive and Hp-negative groups using Fisher exact test, chi-square test and Student's t-test. Univariate and multiple logistic regression analyses were used to identify significant risk factors associated with ID and IDA. RESULTS: One hundred and three subjects (19.7%) had Hp infection and 420 (80.3%) were negative for Hp. Sixty-eight (22.1%) out of 307 subjects with available serum iron profile had unexplained ID and 28 (5.4%) out of 510 subjects with available hemoglobin profile had unexplained IDA. No association was found between ID/IDA and Hp infection in univariate and multiple logistic regression analyses. CONCLUSION: We found no association between unexplained ID or IDA and Hp infection in older adult population without peptic ulcer disease or significant upper gastrointestinal source of blood loss.

Once-daily mesalamine granules for maintaining remission of ulcerative colitis: pooled analysis of efficacy, safety, and prognostic factors.

OBJECTIVES: A capsule formulation of mesalamine granules (MG) was developed for once-daily dosing and better compliance. The study aim was to evaluate MG efficacy and tolerability in maintaining ulcerative colitis (UC) remission. METHODS: Pooled analysis of 2 identical phase 3, randomized, double-blind trials of once-daily MG 1.5 g or placebo for up to 6 months. The primary endpoint was percentage of patients remaining relapse-free at month 6 versus placebo. Relapse was defined as revised Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, UC flare, or UC-related adverse event (AE). RESULTS: Data were pooled for patients receiving MG (n = 373) and placebo (n = 189). Significantly more patients were relapse-free at 6 months with MG (79.4%) than placebo (62.4%; P < 0.001) and across subgroups based on select demographic and baseline characteristics (P < 0.05). Secondary outcome measures including rectal bleeding, physician rating of disease activity, stool frequency, total SDAI score, and relapse-free duration favored MG (P < 0.01). Common AEs with MG and placebo, respectively, were headache (10.9% and 7.6%), diarrhea (7.9% and 7.0%), and abdominal pain (6.3% and 6.5%). CONCLUSION: Once-daily MG was more efficacious than and as well tolerated as placebo in maintaining UC remission. ClinicalTrials.gov identifiers: NCT00744016 and NCT00767728.

Study on wound healing activity of Punica granatum peel.

The methanolic extract of dried pomegranate (Punica granatum) peels showed the presence of a high content of phenolic compounds (44.0%) along with other constituents. This extract was formulated as a 10% (wt/wt) water-soluble gel and was studied for its wound healing property against an excision wound on the skin of Wistar rats. The activity was compared with that of a commercial topical antibacterial applicant. The wound healing activity was assessed by measuring the percent contraction in skin and estimation of collagen content in terms of hydroxyproline content. Healed skin was also subjected to histopathological studies to examine the microscopic changes. The animals treated with 2.5% gel showed moderate healing (55.8% and 40.8% healing compared with negative and positive controls, respectively), whereas the group treated with 5.0% gel showed good healing (59.5% and 44.5% healing compared with negative and positive controls, respectively). The amount of hydroxyproline increased by twofold in the group treated with 5.0% gel. Histopathological studies also supported the wound healing on application of the gels. The group of rats that received 5.0% gel showed complete healing after 10 days, whereas in rats treated with 2.5% gel, healing was observed on day 12, in contrast to the positive control animals receiving the blank gel, which took 16-18 days for complete healing. The results of this study may be extended to different types of wounds so that the formulation could be exploited to develop it as a topical dermatological formulation. High-performance liquid chromatography analysis of the extract showed the presence of gallic acid and catechin as major components.

Bleeding risk after invasive procedures in aspirin/NSAID users: polypectomy study in veterans.

BACKGROUND: Aspirin, by virtue of inhibition of platelet hemostatic function, is withheld before many invasive procedures because of the bleeding risk. American Society of Gastrointestinal Endoscopy guidelines acknowledge the paucity of "high quality data" to make recommendations regarding the use of aspirin (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) before endoscopic procedures. Yet the majority of endoscopists hold ASA/NSAIDs before polypectomy. METHODS: This single-center, retrospective, cohort study was conducted at Veterans Affairs Medical Center, Syracuse, NY. The objectives were to assess the postpolypectomy bleeding risk in ASA/NSAID users in a large cohort of veterans undergoing colonoscopic polypectomy and to identify risk factors associated with postpolypectomy bleeding. All patients undergoing polypectomy between January 2002 and October 2007 were eligible. Patients on anticoagulants/other antiplatelet agents were excluded. Patients were selected randomly by cluster sampling techniques. Electronic medical and pharmacy records were reviewed for patient demographics, polypectomy techniques, and postpolypectomy bleeding rates. Univariate analysis was performed between patients on ASA and NSAIDs (group A) versus those not on ASA or NSAIDs (group B). Multiple regression analysis was performed to identify independent risk factors associated with postpolypectomy bleeding. RESULTS: Five hundred two (43%) of 1174 patients (mean age 66 years, 92% white) were on ASA or NSAIDs, or both. There was no significant difference between postpolypectomy bleeding rates among the 2 groups (3.2% vs 3.0%). Age, sex, polyp characteristics, and polypectomy techniques were comparable between groups A and B. In multiple logistic regression analysis, ASA or NSAID use was not a significant risk factor for postpolypectomy bleeding. Number of polyps removed per patient was the only risk factor significantly associated with postpolypectomy bleeding (P <.01, odds ratio 1.3, 95% confidence interval, 1.18-1.43). CONCLUSIONS: In this large study, use of ASA or NSAIDs did not increase the risk of postpolypectomy bleeding. Cessation of ASA/NSAIDs before colonoscopy/polypectomy is therefore unnecessary.

Successful medical management of emphysematous gastritis with concomitant portal venous air: a case report.

INTRODUCTION: The causes of diffuse abdominal pain following pelvic surgery are numerous. We present a rare case of acute abdominal pain in a woman in the post-partum period. CASE PRESENTATION: A 25-year-old Caucasian woman with neurofibromatosis type 1 presented to our hospital with diffuse abdominal pain immediately after a cesarean section. The patient was acutely ill and toxic with a fever of 38.8 degrees C, a pulse of 120 beats per minute and a distended abdomen with absent bowel sounds. A computed tomography scan showed air in the wall of the stomach and portal venous system. The patient was successfully treated with intravenous antibiotics, bowel rest and total parenteral nutrition. CONCLUSION: It is rare for a case of emphysematous gastritis associated with portal venous air to be treated successfully without surgery. To the best of our knowledge, to date there has been no reported association of emphysematous gastritis with neurofibromatosis.

An unusual presentation of cirrhotic pleural effusion in a patient with no ascites: a case report.

Pleural effusion that develops in a patient with cirrhosis and portal hypertension, in the absence of cardiopulmonary disease, is termed hepatic hydrothorax. Hepatic hydrothorax very rarely presents in the absence of ascites. Although the exact mechanism is somewhat controversial, pleural effusion occurs when ascitic fluid moves through diaphragmatic defects which are opened up by increased intra-abdominal pressure. We report a case report of cirrhotic pleural effusion in a patient with no clinical or radiographic evidence of ascites and discuss the pathogenesis, diagnosis and management of this condition.