Olmesartan-induced enteropathy.

Olmesartan-induced enteropathy (OIE) typically presents with a constellation of signs and symptoms including chronic diarrhoea, weight loss and villous atrophy on biopsy. We describe a 68-year-old Caucasian woman with a history of hypothyroidism and hypertension who presented to our hospital with recurrent episodes of acute intermittent diarrhoea, nausea, vomiting, renal failure and 15 lbs weight loss. After an extensive workup, she was diagnosed with possible OIE. Cessation of the offending drug resulted in improvement of clinical symptoms and also hospital admissions for severe diarrhoea reinforcing the diagnosis of OIE. Among the adverse effects of drug therapy, diarrhoea is a relatively frequent adverse event accounting for about 7%. This report serves as an addition to existing literature and to increase the awareness of olmesartan-induced sprue-like enteropathy among the primary care physicians and gastroenterologists.

The impact of diet liberalization on bowel preparation for colonoscopy.

Background and study aims Dietary restrictions are integral to colonoscopy preparation and impact patient satisfaction. Utilizing split-dose, lower-volume polyethylene glycol 3350-electrolyte solution (PEG-ELS), this study compared colon preparation adequacy of a low-residue diet to clear liquids using a validated grading scale. Patients and methods This was a prospective, randomized, single-blinded, single-center non-inferiority study evaluating diet the day prior to outpatient colonoscopy. Subjects were randomized to a Low-Residue diet for breakfast and lunch, or Clears only. All subjects received split dose PEG-ELS. The primary endpoint was preparation adequacy using the Boston Bowel Preparation Scale (BBPS), with adequate defined as a score > 5. Secondary endpoints included mean BBPS scores for the entire colon and individual segments, satisfaction, adverse events, polyp and adenoma detection rates, and impact on sleep and daily activities. Results Final analysis included 140 subjects, 72 assigned to Clears and 68 to Low-Residue. The Low-Residue diet was non-inferior to Clears (risk difference = - 5.08 %, P = 0.04) after adjusting for age. Mean colon cleansing scores were not significantly different overall and for individual colonic segments. Satisfaction with the Low-Residue diet was significantly greater (P = 0.01). The adenoma detection rate was not statistically significantly different between study groups, but the number of adenomas detected was significantly greater with Clears (P = 0.01). Adverse events and impact on sleep and activities did not differ significantly between diet arms. Conclusions A low-residue diet for breakfast and lunch the day prior to colonoscopy was non-inferior to clear liquids alone for achieving adequate colon cleansing when using split dose PEG-ELS.

Role of muscarinic-3 receptor antibody in systemic sclerosis: correlation with disease duration and effects of IVIG.

Gastrointestinal dysmotility in systemic sclerosis (SSc) is associated with autoantibodies against muscarinic-3 receptor (M3-R). We investigated the temporal course of the site of action of these autoantibodies at the myenteric neurons (MN) vs. the smooth muscle (SM) M3-R in relation to disease duration, and determined the role of intravenous immunoglobulin (IVIG) in reversing these changes. Immunoglobulins purified from SSc patients (SScIgG) were used to assess their differential binding to MN and SM (from rat colon) employing immunohistochemistry (IHC). Effect of SScIgG on neural and direct muscle contraction was determined by cholinergic nerve stimulation and bethanechol-induced SM contraction. Effects of IVIG and its antigen-binding fragment F(ab')2 on SScIgG binding were studied by enzyme-linked immunosorbent assay (ELISA) of rat colonic longitudinal SM myenteric plexus (LSMMP) lysate and to second extracellular loop peptide of M3-R (M3-RL2). SScIgG from all patients demonstrated significantly higher binding to MN than to SM. With progression of SSc duration, binding at MN and SM increased in a linear fashion with a correlation coefficient of 0.696 and 0.726, respectively (P < 0.05). SScIgG-mediated attenuation of neural and direct SM contraction also increased with disease duration. ELISA analysis revealed that IVIG and F(ab')2 significantly reduced SScIgG binding to LSMMP lysate and M3-RL2. Dysmotility in SSc occurs sequentially, beginning with SScIgG-induced blockage of cholinergic neurotransmission (neuropathy), which progresses to inhibition of acetylcholine action at the SM cell (myopathy). IVIG reverses this cholinergic dysfunction at the neural and myogenic receptors by anti-idiotypic neutralization of SScIgG.

Spiral Enteroscopy Utilizing Capsule Location Index for Achieving High Diagnostic and Therapeutic Yield.

Background and Aim. Spiral enteroscopy (SE) is a new small bowel endoscopic technique. Our aim is to review the diagnostic and therapeutic yield, safety of SE, and the predictive role of prior capsule endoscopy (CE) at an academic center. Methods. A retrospective review of patients undergoing SE after prior CE between 2008 and 2013 was performed. Capsule location index (CLI) was defined as the fraction of total small bowel transit time when the lesion was seen on CE. Results. A total of 174 SEs were performed: antegrade (147) and retrograde (27). Abnormalities on SE were detected in 65% patients. The procedure was safe in patients with surgically altered bowel anatomy (n = 12). The diagnostic yield of antegrade SE decreased with increasing CLI range. The diagnostic yield of retrograde SE decreased on decreasing CLI range. A CLI cutoff of 0.6 was derived that determined the initial route of SE. Vascular ectasias seen on CE were detected in 83% cases on SE; p < 0.01. Conclusions. SE is safe with a high diagnostic and therapeutic yield. CLI is predictive of the success of SE and determines the best route of SE. The type of small bowel pathology targeted by SE may affect its utility and yield.

Low but significant yield of endosonography in patients with suspected Sphincter of Oddi Dysfunction Type III with normal imaging studies.

AIM: To determine the yield of endosonography (EUS) in patients with suspected Sphincter of Oddi Dysfunction (SOD) Type III in detecting abdominal abnormalities in those with normal upper endoscopy and imaging studies. METHODS: A retrospective review of patients with suspected SOD who underwent EUS prior to undergoing an ERCP was performed. The inclusion criteria were: 1. patients with right upper quadrant abdominal pain for >/= 3 months; 2. no evidence of abnormalities on upper endoscopy, imaging studies and laboratory tests. Exclusion criteria were: history of acute or chronic pancreatitis, pancreas divisum, jaundice or any significant abnormality detected on prior studies. The main outcome measurements were to determine the diagnostic yield of EUS to diagnose the etiology of abdominal pain and detect clinically significant lesions. RESULTS: We identified 143 patients with suspected SOD type III who had undergone EUS. A diagnosis of the etiology of abdominal pain by EUS was made in 12 of 143 patients (8%) with previously normal endoscopy and imaging studies. EUS identified the following: changes consistent with chronic pancreatitis (n=5), biliary stone (n=1), side-branch intraductal papillary mucinous neoplasms of the pancreas (n=3), benign bile duct stricture (n=1). Papillary stenosis was diagnosed in two patients with common bile duct dilation detected by EUS. CONCLUSIONS: EUS may detect significant abnormalities in a small subset of patients with suspected SOD with previous normal endoscopies and imaging studies. Although the yield of EUS is low, it should be considered in patients with persistent pain and those with a high clinical suspicion for pancreatic pathology.

Long-term use of angiotensin converting enzyme inhibitors is associated with decreased incidence of advanced adenomatous colon polyps.

BACKGROUND: The long-term use of angiotensin converting enzyme (ACE) inhibitors may reduce the risk of developing colorectal cancer (CRC). GOAL: The aim of our study was to determine how long-term use of lisinopril influences the development of advanced adenomatous polyps (APs). STUDY: We performed a retrospective study of patients who were found to have 1 or more histologically confirmed APs on an index colonoscopy, and who also had a follow-up colonoscopy 3 to 5 years later. APs found on the follow-up colonoscopy were evaluated for location, size, number, and advanced features. Patients were divided into 2 groups: (1) those who used lisinopril continuously during the interval between colonoscopies and (2) those who were lisinopril naive. Clinical factors were evaluated for their association with advanced APs in both the groups. RESULTS: A total of 4660 patients with a history of AP were identified. There were 1760 continuous lisinopril users and 2900 nonusers. Univariate analysis showed that patients with lisinopril use had fewer right-side APs (odds ratio=0.68, P<0.001) and fewer total number of APs (P<0.001). Lisinopril users had a 41% reduced incidence of advanced APs compared with the nonusers (odds ratio=0.59, P<0.001). A Mann-Whitney U test revealed that among lisinopril users, patients with advanced APs were on a lower dose of the medication compared with patients without advanced APs (mean dose=17.2 mg vs. 20.1 mg, respectively; P<0.001). Spearman correlation analyses indicated an inverse relationship between lisinopril dosage and number of polyps (P<0.001). There was also an inverse relationship between dosage and size of polyps (P<0.001); higher dosages of lisinopril were significantly associated with smaller size of polyps. The protective effect of lisinopril was significant even when adjusted for age, body mass index, aspirin/nonsteroidal anti-inflammatory drug use, and statin use. CONCLUSIONS: The use of lisinopril was associated with a 41% reduction in the incidence of advanced APs during a period of 3 to 5 years, even after adjustment for other known polyp risk factors. We speculate that long-term ACE inhibitors use may reduce the development of CRCs by reducing the development of advanced APs.

A previous cholecystectomy increases the risk of developing advanced adenomas of the colon.

BACKGROUND: There is limited data assessing the relationship between cholecystectomy and colorectal adenomatous polyps (AP). Our aim was to determine if cholecystectomy was associated with an increased prevalence of advanced AP in male veterans. METHODS: The relationship of whether prior cholecystectomy modified the natural history of AP was investigated in a retrospective study. The patients were divided into two groups: 1) those with AP and a history of cholecystectomy, and 2) those with AP, but without a history of cholecystectomy. Factors in each group associated with advanced AP were examined by univariate analysis (UA) and stepwise logistic regression analysis to determine independent predictors of aggressive clinical characteristics of polyps. Statistical significance was determined at a P < or = 0.05. RESULTS: We identified a total of 1234 patients with AP (cases = 127, controls = 1107). The mean age of patients was 64.1 +/- 1.9 (standard deviation) years. By UA, those with a prior cholecystectomy had a greater mean number of AP (4.2 vs. 3.5; P = 0.04) and more advanced polyps (P = 0.037) than those without a cholecystectomy. By logistic regression, prior cholecystectomy was associated with more advanced AP (OR = 1.5 [1.0-2.2]; P = 0.04). Patients who had a cholecystectomy were 51% more likely to have advanced AP. There appeared to be a trend towards increased time from cholecystectomy being associated with advanced polyps (9.69 years vs. 8.99 years, P = 0.056). CONCLUSIONS: A prior cholecystectomy was independently associated with an increased risk of developing advanced AP. Also, there appeared to be a trend toward a greater prevalence of advanced lesions as postcholecystectomy time increased.

Potential anti-inflammatory effects of proton pump inhibitors: a review and discussion of the clinical implications.

Proton pump inhibitors (PPIs) are potent blockers of gastric acid secretion, and are widely regarded as the agents of choice for the treatment of acid-peptic disorders. For patients with upper gastrointestinal symptoms of uncertain etiology, improvement with PPI therapy is considered prima facie evidence of a pathogenetic role for acid-peptic disease. In addition to anti-secretory effects, however, PPIs have been found to have anti-oxidant properties and direct effects on neutrophils, monocytes, endothelial, and epithelial cells that might prevent inflammation. Those anti-inflammatory effects of the PPIs might influence a variety of inflammatory disorders, both peptic and non-peptic, within and outside of the gastrointestinal tract. The purpose of this report is to review the mechanisms whereby PPIs might exert anti-inflammatory effects exclusive of gastric acid inhibition, to discuss the clinical implications of those effects, and to emphasize that a clinical response to PPIs should not be construed as proof for an underlying acid-peptic disorder.

Effect of percentage of positive prostate biopsy cores on biochemical outcome in low-risk PCa treated with brachytherapy or 3D-CRT.

OBJECTIVES: To investigate the significance of the percentage of positive biopsy cores (PPBCs) in predicting the biochemical outcome in patients with low-risk prostate cancer undergoing brachytherapy or three-dimensional conformal external beam radiotherapy (3D-CRT). METHODS: We retrospectively reviewed 360 patients with low-risk prostate cancer who had undergone low dose-rate brachytherapy ((125)I) or 3D-CRT from 1993 to 2006. Of the 360 patients, 189 had undergone 3D-CRT and 171 had undergone brachytherapy. The patients were stratified according to treatment modality and PPBCs (<34%, 34%-50%, >50%). Biochemical failure was defined by the 2006 Radiation Therapy Oncology Group-American Society for Therapeutic Radiology and Oncology, Phoenix Consensus Conference definition. RESULTS: The median follow-up in the 3D-CRT and brachytherapy groups was 51 and 37 months, respectively. The number of patients who had a PPBCs of <34%, 34%-50%, and >50% in the 3D-CRT and brachytherapy cohorts was 154, 26, and 9 and 133, 25, and 15, respectively. The 5-year freedom from biochemical failure rate for 3D-CRT and brachytherapy was 95% and 96%, respectively; the corresponding median prostate-specific antigen nadirs were 0.7 and 0.3 ng/mL (P < .001). No significant differences were found in age, stage, Gleason score, or PPBCs between the 2 cohorts. Cox regression analysis showed that the pretreatment prostate-specific antigen level, stage, PPBCs, and treatment modality did not predict for the time to biochemical failure. When stratified by PPBCs, no significant difference in FFBF for either modality was seen. CONCLUSIONS: In patients with low-risk prostate cancer, brachytherapy and 3D-CRT remain excellent treatment choices, regardless of the tumor volume as estimated by the PPBCs. Longer follow-up and the recruitment of men with a greater volume of disease (>50% PPBCs) are needed to confirm these preliminary findings.