John M. Wo

Proton Pump Inhibitor Therapy for Suspected GERD-Related Chronic Laryngitis: A Meta-Analysis of Randomized Controlled Trials

OBJECTIVE:The role of proton pump inhibitors (PPIs) in suspected GERD-related chronic laryngitis (CL) is controversial. Hence, we performed a meta-analysis of the existing randomized controlled trials (RCTs) to evaluate the efficacy of PPIs in this disorder.METHODS:Data extracted from MEDLINE (1966 to August 2005), Cochrane Controlled Trials Register (1997 to August 2005), EMBASE (1980 to August 2005), ClinicalTrials.gov website, and meetings presentations (1999–2005). Published and unpublished randomized placebo-controlled trials of PPIs in suspected GERD-related CL were selected by consensus. Random effects model was utilized with standard approaches to quality assessment, sensitivity analysis, and an exploration of heterogeneity and publication bias. The primary outcome measure was defined as the proportion of patients with ≥50% reduction in self-reported laryngeal symptoms.RESULTS:Pooled data from 8 studies (N = 344, PPI 195, placebo 149; mean age 51 yr; males 55%; study duration 8–16 wk) were analyzed. No significant quantitative heterogeneity was found among the studies (χ2 = 11.22, P = 0.13). Overall, PPI therapy resulted in a nonsignificant symptom reduction compared to placebo (relative risk 1.28, 95% confidence interval 0.94–1.74). No clinical predictors of PPI response were identified on meta-regression analysis done at study level.CONCLUSIONS:PPI therapy may offer a modest, but nonsignificant, clinical benefit over placebo in suspected GERD-related CL. Validated diagnostic guidelines may facilitate the recognition of those patients most likely to respond favorably to PPI treatment.

Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects

Background  Gastric emptying scintigraphy (GES) using a radio‐labelled meal is used to measure gastric emptying. A nondigestible capsule, SmartPill, records luminal pH, temperature, and pressure during gastrointestinal transit providing a measure of gastric emptying time (GET).

Gastric Electrical Stimulation With Enterra Therapy Improves Symptoms From Diabetic Gastroparesis in a Prospective Study

BACKGROUND & AIMS Gastric electrical stimulation (GES) treats refractory gastroparesis by delivering electric current, via electrodes, to gastric smooth muscle. Enterra therapy (Medtronic, Inc, Minneapolis, MN) uses an implantable neurostimulator with a high-frequency, low-energy output. We performed a controlled, multicenter, prospective study to evaluate the safety and efficacy of Enterra therapy in patients with chronic intractable nausea and vomiting from diabetic gastroparesis (DGP). METHODS Patients with refractory DGP (n = 55; mean age, 38 y; 66% female, 5.9 years of DGP) were given implants of the Enterra gastric stimulation system. After surgery, all patients had the stimulator turned on for 6 weeks and then they randomly were assigned to groups that had consecutive 3-month, cross-over periods with the device on or off. After this period, the device was turned on in all patients and they were followed up, unblinded, for 4.5 months. RESULTS The median reduction in weekly vomiting frequency (WVF) at 6 weeks, compared with baseline, was 57% (P < .001). There was no difference in WVF between patients who had the device turned on or off during the cross-over period (median reduction, 0%; P = .215). At 1 year, the WVF of all patients was significantly lower than baseline values (median reduction, 67.8%; P < .001). Patients also had significant improvements in total symptom score, gastric emptying, quality of life, and median days in the hospital. CONCLUSIONS In patients with intractable DGP, 6 weeks of GES therapy with Enterra significantly reduced vomiting and gastroparetic symptoms. Patients had improvements in subjective and objective parameters with chronic stimulation after 12 months of GES, compared with baseline.

Significance of Intestinal Metaplasia in Different Areas of Esophagus Including Esophagogastric Junction

Over the past two decades, the incidence ofadenocarcinoma of the esophagus and gastric cardia hasincreased at a rate exceeding that of any other cancer.Barretts esophagus is the only known risk factor for these malignancies. Recently, emphasis hasbeen placed on the significance of specializedintestinal metaplasia (SIM) on esophageal biopsies. Ouraim was to compare the prevalence of SIM at different esophageal locations in patients who are athigher risk of developing esophageal adenocarcinoma(Caucasians) and patients with lower risk of developingesophageal adenocarcinoma (African-Americans).Eighty-seven unselected patients (42 Caucasians and 45African-Americans) underwent routine upper endoscopywith biopsies from the proximal margin of columnarmucosa. We classified patients into those with acolumnar-lined esophagus with SIM (CLE with SIM); CLE withoutSIM; or SIM with a normal-appearing gastroesophagealjunction (SIM-GEJ). The prevalence of CLE with SIM, CLEwithout SIM, and SIM-GEJ was 28%, 10%, and 10% in Caucasians compared to 0%, 18% and 11% inAfrican-Americans (P = 0.0001, 0.26, and 0.81,respectively). We found CLE with SIM only in patientswith reflux symptoms at least twice a week. It isconcluded that CLE with SIM is seen most commonly inpatients thought to be at risk for esophagealadenocarcinoma (Caucasians with reflux symptoms). It israrely seen in other groups with lower risk for thismalignancy (African-Americans, nonrefluxers). Conversely,SIM-GEJ and CLE without SIM are common in all groups andare of questionable significance.

Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: a randomized, placebo-controlled study

Background  Gastroparesis, a chronic disorder of abnormal gastric motility, is common in patients with diabetes mellitus. A synthetic, selective ghrelin receptor agonist, TZP‐101, is in clinical development for treatment of gastroparesis. This double‐blind, randomized, placebo‐controlled study evaluated the safety and efficacy of multiple TZP‐101 doses in patients with moderate to severe symptomatic diabetic gastroparesis.

Double-Blind, Placebo-Controlled Trial with Single-Dose Pantoprazole for Laryngopharyngeal Reflux

OBJECTIVES:Results of randomized treatment trials for laryngopharyngeal reflux (LPR) are mixed. The cause and effect between gastroesophageal reflux and laryngeal symptoms remain elusive.AIMS:To determine the efficacy of single-dose pantoprazole in newly diagnosed LPR and to correlate hypopharyngeal reflux with symptom improvement.METHODS:Randomized, double-blind, placebo-controlled trial was performed with a 2-wk run-in, 12-wk treatment period (pantoprazole 40 mg q.a.m. or placebo), and 4-wk follow-up. Study criteria were laryngeal complaints >3 days/wk and a positive triple-sensor pH test. Laryngeal exam was graded using a reflux finding score before and after treatment. Repeat pH test was performed on study drug at week 12. Weekly diaries were kept on symptom severity and global assessment. Total laryngeal symptom score was defined as the sum of six laryngeal symptoms. Mann-Whitney U, Wilcoxon, and Pearson tests were used.RESULTS:Thirty-nine subjects (13 M/26 F, median age 39 yr) were randomized; 35 completed the study. During the treatment period, total laryngeal symptom scores significantly improved compared with pretreatment scores in both study groups, but there were no significant differences between them. Forty percent of pantoprazole group reported adequate relief at week 12, compared with 42% of placebo group (p = 0.89). No significant improvement in hypopharyngeal reflux was found in either study group. There were no significant correlations between laryngeal reflux finding scores and hypopharyngeal reflux episodes with symptom improvement.CONCLUSIONS:Response was similar between single-dose pantoprazole and placebo in newly diagnosed LPR. Our results suggested that laryngeal exam was not useful in following treatment response. Hypopharyngeal reflux may represent acid reflux or artifacts, but is not likely the underlying cause.

Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule.

Background  The wireless motility capsule (WMC) measures intraluminal pH and pressure, and records transit time and contractile activity throughout the gastrointestinal tract. Our hypothesis is that WMC can differentiate antroduodenal pressure profiles between healthy people and patients with upper gut motility dysfunctions.

Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis

BACKGROUND & AIMS It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.

A phase 2a, randomized, double‐blind 28‐day study of TZP‐102 a ghrelin receptor agonist for diabetic gastroparesis

Background  Gastroparesis causes significant morbidity and treatment options are limited. TZP‐102 a novel, macrocyclic, selective, oral ghrelin receptor agonist, was evaluated in a randomized, double‐blind, placebo‐controlled trial in patients with diabetic gastroparesis.

Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting – randomised clinical study subset data

Aliment Pharmacol Ther 2011; 33: 679–688