Ideal strategy for nonvariceal upper gastrointestinal bleeding.

PURPOSE OF REVIEW: Over 300 000 hospital admissions in the United States each year are due to patients with upper gastrointestinal (GI) bleeding (UGIB). Common etiologies of nonvariceal UGIB include peptic ulcers, mucosal erosions of the esophagus, stomach or duodenum, Mallory-Weiss tears, Dieulafoy lesions, upper GI tract malignancy, or other etiology. RECENT FINDINGS: Peptic ulcers classified as Forrest Ia, Ib, or IIa require endoscopic hemostasis, while IIb ulcers may be considered for endoscopic clot removal with endoscopic treatment of any underlying major stigmata. Endoscopic hemostasis for ulcers classified as Forrest IIc or III is not advised due to the low risk of recurrent bleeding. Endoscopic hemostasis in ulcer bleeding can be achieved using injection, thermal, and/or mechanical modalities. SUMMARY: This review focuses on the currently recommended endoscopic therapies of patients presenting with acute nonvariceal upper gastrointestinal hemorrhage.

ACG Clinical Guidelines: Diagnosis and Management of Achalasia.

Achalasia is an esophageal motility disorder characterized by aberrant peristalsis and insufficient relaxation of the lower esophageal sphincter. Patients most commonly present with dysphagia to solids and liquids, regurgitation, and occasional chest pain with or without weight loss. High-resolution manometry has identified 3 subtypes of achalasia distinguished by pressurization and contraction patterns. Endoscopic findings of retained saliva with puckering of the gastroesophageal junction or esophagram findings of a dilated esophagus with bird beaking are important diagnostic clues. In this American College of Gastroenterology guideline, we used the Grading of Recommendations Assessment, Development and Evaluation process to provide clinical guidance on how best to diagnose and treat patients with achalasia.

Assessment of provider-perceived barriers to clinical use of pharmacogenomics during participation in an institutional implementation study.

OBJECTIVE: The objective of this study was to study provider attitudes of and perceived barriers to the clinical use of pharmacogenomics before and during participation in an implementation program. PARTICIPANTS AND METHODS: From 2012 to 2017, providers were recruited. After completing semistructured interviews (SSIs) about pharmacogenomics, providers received training on and access to a clinical decision support tool housing patient-specific pharmacogenomic results. Thematic analysis of SSI was conducted (inter-rater reliability κ≥0.75). Providers also completed surveys before and during study participation, and provider-perceived barriers to pharmacogenomic implementation were analyzed. RESULTS: Seven themes emerged from the SSI (listed from most frequent to least): decision-making, concerns with pharmacogenomic adoption, outcome expectancy, provider knowledge of pharmacogenomics, patient attitudes, individualized treatment, and provider interest in pharmacogenomics. Although there was prestudy enthusiasm among all providers, concerns with clinical utility, time, results accession, and knowledge of pharmacogenomics were frequently stated at baseline. Despite this, adoption of pharmacogenomics was robust, as patient-specific results were accessed at 64% of visits, and medication changes were influenced by provided pharmacogenomic information 42% of the time. Providers reported they had enough time to evaluate the information and the results were easily understood on 74 and 98% of surveys, respectively. Nevertheless, providers consistently felt there was insufficient pharmacogenomic information for most drugs they prescribed and clear guidelines for using pharmacogenomic information were lacking. CONCLUSION: Despite initial concerns about adequate time and knowledge for adoption, providers frequently utilized pharmacogenomic results. Provider-perceived barriers to wider use included lack of clear guidelines and evidence for most drugs, highlighting important considerations for the field of pharmacogenomics.

Patient-provider communications about pharmacogenomic results increase patient recall of medication changes.

Effective doctor-patient communication is critical for disease management, especially when considering genetic information. We studied patient-provider communications after implementing a point-of-care pharmacogenomic results delivery system to understand whether pharmacogenomic results are discussed and whether medication recall is impacted. Outpatients undergoing preemptive pharmacogenomic testing (cases), non-genotyped controls, and study providers were surveyed from October 2012-May 2017. Patient responses were compared between visits where pharmacogenomic results guided prescribing versus visits where pharmacogenomics did not guide prescribing. Provider knowledge of pharmacogenomics, before and during study participation, was also analyzed. Both providers and case patients frequently reported discussions of genetic results after visits where pharmacogenomic information guided prescribing. Importantly, medication changes from visits where pharmacogenomics influenced prescribing were more often recalled than non-pharmacogenomic guided medication changes (OR = 3.3 [1.6-6.7], p = 0.001). Case patients who had separate visits where pharmacogenomics did and did not, respectively, influence prescribing more often remembered medication changes from visits where genomic-based guidance was used (OR = 3.4 [1.2-9.3], p = 0.02). Providers also displayed dramatic increases in personal genomic understanding through program participation (94% felt at least somewhat informed about pharmacogenomics post-participation, compared to 61% at baseline, p = 0.04). Using genomic information during prescribing increases patient-provider communications, patient medication recall, and provider understanding of genomics, important ancillary benefits to clinical use of pharmacogenomics.

Efficacy of Pharmacologic Therapy for Eosinophilic Esophagitis: A Systematic Review and Network Meta-Analysis.

GOALS: In order to provide a comparative evaluation of available pharmacologic treatments for eosinophilic esophagitis (EoE), we conducted a network meta-analysis. BACKGROUND: A variety of pharmacologic treatments for EoE have been reported, however there exists a paucity of direct comparisons. STUDY: We searched randomized controlled trials using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials database through December 2014. Studies were analyzed using a random-effects network meta-analysis to identify the most effective therapy. Subgroup analysis was performed among studies that excluded gastroesophageal reflux disease or proton-pump inhibitor responsive esophageal eosinophilia, and also among pediatric and adult populations. The ranking probability for the efficacy of each treatment was analyzed. Consistency of the included randomized controlled trials was checked by applying inconsistency and node-splitting models. RESULTS: Eleven studies of a total of 456 patients were identified. Six pharmacologic treatments (budesonide suspension and viscous, fluticasone, prednisone, esomeprazole, and mepolizumab) and placebo were included in our analysis. Meta-analysis showed superiority of budesonide viscous, budesonide suspension, and fluticasone over placebo. Network meta-analysis demonstrated the rank order of efficacy as budesonide viscous, esomeprazole, prednisone, budesonide suspension, fluticasone, mepolizumab, and placebo. The results were consistent from the inconsistency model analysis and node-splitting analysis. Subgroup analysis demonstrated prednisone, budesonide suspension, and esomeprazole were the most effective when network meta-analyses were performed among studies that excluded gastroesophageal reflux disease or proton-pump inhibitor responsive esophageal eosinophilia, and among pediatric and adult populations, respectively. CONCLUSIONS: On the basis of this network meta-analysis, viscous budesonide was shown to be the most effective pharmacologic therapy for EoE among the reported pharmacologic treatments.

Mucosal impedance discriminates GERD from non-GERD conditions.

BACKGROUND & AIMS: Current diagnostic tests for gastroesophageal reflux disease (GERD) are suboptimal and do not accurately and reliably measure chronicity of reflux. A minimally invasive device has been developed to assess esophageal mucosal impedance (MI) as a marker of chronic reflux. We performed a prospective longitudinal study to investigate MI patterns in patients with GERD and common nonreflux conditions, to assess MI patterns before and after treatment with proton pump inhibitors and to compare the performance of MI and wireless pH tests. METHODS: We evaluated MI in 61 patients with erosive esophagitis, 81 with nonerosive but pH-abnormal GERD, 93 without GERD, 18 with achalasia, and 15 with eosinophilic esophagitis. MI was measured at the site of esophagitis and at 2, 5, and 10 cm above the squamocolumnar junction in all participants. MI was measured before and after acid suppressive therapy, and findings were compared with those from wireless pH monitoring. RESULTS: MI values were significantly lower in patients with GERD (erosive esophagitis or nonerosive but pH-abnormal GERD) or eosinophilic esophagitis than in patients without GERD or patients with achalasia (P < .001). The pattern of MI in patients with GERD differed from that in patients without GERD or patients with eosinophilic esophagitis; patients with GERD had low MI closer to the squamocolumnar junction, and values increased axially along the esophagus. These patterns normalized with acid suppressive therapy. MI patterns identified patients with esophagitis with higher levels of specificity (95%) and positive predictive values (96%) than wireless pH monitoring (64% and 40%, respectively). CONCLUSIONS: Based on a prospective study using a prototype device, measurements of MI detect GERD with higher levels of specificity and positive predictive values than wireless pH monitoring. Clinical Trials.gov, Number: NCT01556919.

Use of direct, endoscopic-guided measurements of mucosal impedance in diagnosis of gastroesophageal reflux disease.

BACKGROUND & AIMS: Diagnostic tests for gastroesophageal reflux disease (GERD) are constrained because measurements are made at a single time point, so the long-term effects on the mucosa cannot be determined. We developed a minimally invasive system to assess changes in esophageal mucosal impedance (MI), a marker of reflux. We measured the extent of changes in MI along the esophagus and show that the device to assess MI can be used to diagnose patients with GERD. METHODS: A single-channel MI catheter composed of a unique sensor array was designed to easily traverse the working channel of an upper endoscope. We performed a prospective longitudinal study of patients with erosive esophagitis (n = 19), nonerosive but pH-positive GERD (n = 23), and those without GERD (n = 27). MI was measured at the site of esophagitis as well as 2, 5, and 10 cm above the squamocolumnar junction. The MI values were compared among groups, at different levels along the esophageal axis. RESULTS: Median MI values were significantly lower at the site of erosive mucosa (811 Ω; range, 621-1272 Ω) than other nonerosive regions (3723 Ω; range, 2421-4671 Ω; P = .001), and were significantly lower at 2 cm above the squamocolumnar junction in patients with GERD (2096 Ω; range, 1415-2808 Ω), compared with those without GERD (3607 Ω; range, 1973-4238 Ω; P = .008). There was a significant and graded increase in MI along the axis of the distal to proximal esophagus in patients with GERD that was not observed in individuals without reflux (P = .004). CONCLUSIONS: Measurements of MI along the esophagus can be used to identify patients with GERD. ClinicalTrials.gov, number NCT01194323.

Symptom reports are not reliable during ambulatory reflux monitoring.

OBJECTIVES: Patient reporting of symptom events during ambulatory reflux monitoring is commonly performed with little data regarding its accuracy. We employed a novel time-synchronized ambulatory audio recording of symptom events simultaneously with prolonged pH/impedance monitoring to assess temporal accuracy of patient-reported symptoms. METHODS: An acoustic monitoring system was employed to detect cough events via tracheal and chest wall sounds and it was temporally synchronized with an ambulatory impedance/pH monitoring system. Patients were instructed to record their symptoms in the usual manner. Six separate observers independently listened to the 24-h audio recordings and logged the exact timing of each cough event. Patients were blinded to study design and the audio reviewers were blinded to their own reports and those of patients and other reviewers. Concurrence of audio recordings and patient-reported symptoms were tested for three separate time thresholds: 1, 2, and 5 min. RESULTS: The median (interquartile range (IQR)) number of cough events by audio detection was significantly (P<0.001) higher than those reported by patients: 216 (90-275) and 34 (22-60), respectively. There was significantly (P<0.001) higher agreement among the audio recording listeners (substantial to almost perfect agreement; kappa=0.77-0.82) than between the audio recording and patient-reported symptoms (slight to fair agreement; kappa=0.13-0.27). Patients did not report 91, 82, and 71% of audible cough events based on 1-, 2-, and 5-min concordance time windows, respectively. CONCLUSIONS: We found that patients do not report the majority of their symptoms during ambulatory reflux monitoring even within a 5-min time window of the true event and advise caution in clinical decision-making based solely on symptom indices.

Diagnosis and Treatment of Peptic Ulcer Disease.

Peptic ulcer disease continues to be a source of significant morbidity and mortality worldwide. Approximately two-thirds of patients found to have peptic ulcer disease are asymptomatic. In symptomatic patients, the most common presenting symptom of peptic ulcer disease is epigastric pain, which may be associated with dyspepsia, bloating, abdominal fullness, nausea, or early satiety. Most cases of peptic ulcer disease are associated with Helicobacter pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs), or both. In this review, we discuss the role of proton pump inhibitors in the management of peptic ulcer disease, highlight the latest guidelines about the diagnosis and management of H. pylori, and discuss the latest evidence in the management of complications related to peptic ulcer disease, including endoscopic intervention for peptic ulcer-related bleeding. Timely diagnosis and treatment of peptic ulcer disease and its sequelae are crucial in order to minimize associated morbidity and mortality, as is prevention of peptic ulcer disease among patients at high risk, including those infected with H. pylori and users of NSAIDs.

Cerebral edema and hyperammonemia after transjugular intrahepatic portosystemic shunt placement in a cirrhotic patient.

Transjugular intrahepatic portosystemic shunt (TIPS) placement has been widely performed for nearly two decades and has been shown to alleviate refractory ascites in patients with cirrhosis. Hepatic encephalopathy after TIPS is rarely severe; however, a risk of cerebral edema resulting from hyperammonemia after TIPS does exist. Here we describe a case demonstrating the development of severe hepatic encephalopathy with cerebral edema caused by hyperammonemia as a complication of TIPS in a patient with chronic liver disease with relatively preserved liver function.

Demographic Features of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an increasingly prevalent chronic condition characterized by eosinophilic infiltration of the esophageal epithelium accompanied by esophageal symptoms. The number of new diagnoses is growing worldwide in both pediatric and adult populations. Differences in disease distribution and presentation have been found, varying by gender, race, and other characteristics. This review examines the existing literature and provides insight into the demographic features of EoE.

The Role of Allergy Testing in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is defined as a chronic, immune/antigen-mediated esophageal disease that can lead to symptoms of esophageal dysfunction. This disease is seen in both children and adults. Approximately 70% of patients with EoE have food antigen sensitization or other atopic conditions, suggesting an allergic etiology in the pathogenesis of the disease. The role of allergy testing to identify foods that lead to EoE is unclear. Three types of allergy tests currently exist: skin prick testing, atopy patch testing, and immunoassays for serum food-specific immunoglobulin E. It is important for gastroenterologists to work in conjunction with allergist colleagues in the care of patients with EoE, particularly in the management of comorbid atopic conditions.

Current Diagnostic and Treatment Strategies for Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus diagnosed by the presence of esophageal symptoms accompanied by an esophageal eosinophilic infiltrate. EoE has an increasing worldwide prevalence and can be a cause of dysphagia and food impactions. There is an important role for the use of proton pump inhibitors in the diagnostic pathway of EoE. Treatment paradigms for EoE aim to minimize esophageal inflammation and improve symptom control. Dietary therapy targets dietary allergens and encompasses the elemental diet, the allergy testing-directed elimination diet, and the empiric elimination diet. Pharmacologic options include topical corticosteroids as the standard first-line treatment. Multiple other pharmacologic interventions are currently under investigation and are not recommended in the most recent guidelines. Endoscopic dilation is usually reserved for patients who relapse on pharmacologic or dietary regimens or who have symptomatic stricturing disease. This article provides a comprehensive discussion of existing diagnostic and management strategies for EoE.

Laparoscopic Antireflux Surgery: Importance of Patient's Selection and Preoperative Workup.

BACKGROUND: Laparoscopic antireflux surgery (LARS) is an excellent option for patients with symptoms refractory to medical treatment, for patients who have complications secondary to the use of proton pump inhibitors, and for those who do not want to take medications for a long period of time. HYPOTHESIS: We hypothesized that (1) LARS has excellent outcomes if a complete preoperative workup and proper patient selection are performed and (2) recurrent symptoms often are not due to failure of the fundoplication to control the pathologic reflux. PATIENTS AND METHODS: Every patient referred for antireflux surgery underwent a detailed symptomatic evaluation, barium swallow, esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM), and pH monitoring. A fundoplication was performed in all of them. Data were analyzed to determine outcomes across 8 years. RESULTS: From 2008 to 2016, 176 patients with gastroesophageal reflux disease (GERD) underwent LARS. One hundred and thirty-four patients (76.1%) had a total fundoplication, 31 (17.6%) had an anterior partial fundoplication, and 11 (6.3%) had a posterior partial fundoplication. Thirty-nine patients (22.2%) referred persistent or recurrent symptoms after the procedure and underwent EGD, HRM, and pH monitoring. Abnormal reflux was documented in 5 patients (2.8%). Among these failures, 3 patients had a body mass index (BMI) ≥30 and 2 had ≥35. CONCLUSIONS: The results of this study showed that (1) laparoscopic fundoplication is an effective procedure for GERD; (2) patient's BMI can affect the outcome of a fundoplication; and (3) pH monitoring is important to establish if recurrent symptoms are secondary to failure of the operation.

Multidisciplinary Approach to Esophageal Achalasia: A Single Center Experience.

BACKGROUND: The treatment of achalasia is palliative. Pneumatic dilatation (PD) or laparoscopic Heller myotomy (LHM) just eliminates the outflow obstruction allowing easier emptying of the esophagus. The aim of this study was to evaluate the results of a multidisciplinary approach to esophageal achalasia. MATERIALS AND METHODS: A consecutive series of patients with achalasia treated by a multidisciplinary esophageal team consisting of radiologists, gastroenterologists, and surgeons in a quaternary care center between May 2008 and April 2015 were analyzed. RESULTS: A total of 147 patients with achalasia underwent LHM and partial fundoplication. Sixty-two patients (42%) had been treated preoperatively with PD and/or botulinum toxin (BT). The preoperative Eckardt score (ES) was 6.4 ± 2. At a median follow-up of 22 months, 128 patients (87%) did well and required no further treatment (ES 0.1). The remaining 19 patients (13%) had recurrence of symptoms and required further treatment: 12 were treated with PD and improved (ES 0.7); 4 were treated with PD and BT and improved (ES 1.3); 3 failed PD. These 3 patients had been treated with multiple sessions of PD and BT before the myotomy. Overall, 144 patients (98%) did well with laparoscopic (87%) or laparoscopic and endoscopic treatment (11%). CONCLUSIONS: The results of this study show that (a) LHM is an effective treatment modality, (b) PD improved symptoms in the majority of patients with recurrent dysphagia after myotomy and (c) multiple preoperative endoscopic treatments seem to affect outcomes of LHM. Patients with achalasia should be treated in a quaternary care center by a multidisciplinary team.