Measurement of Salivary Pepsin to Detect Gastroesophageal Reflux Disease Is Not Ready for Clinical Application.

A noninvasive test for gastroesophageal reflux disease (GERD) is desirable for adults and children. Salivary pepsin measurement has been proposed as such a test.1-3 A previous study from our group demonstrated that a maximal salivary pepsin cutoff of >210 ng/mL using the PepTest device (RD Biomed, Hull, United Kingdom) had excellent specificity of 96% but modest sensitivity of 44% to diagnose GERD,4 leading to optimism about its potential use. In this study, we aimed to confirm the previously reported sensitivity and specificity in healthy volunteers and patients with heartburn, evaluate the association between a positive PepTest and response to proton pump inhibitor (PPI) therapy, assess if test-sensitivity can be improved for GERD when samples are taken over a 72-hour sampling period, and establish normal values of salivary pepsin in infants.

200 mL Rapid Drink Challenge During High-resolution Manometry Best Predicts Objective Esophagogastric Junction Obstruction and Correlates With Symptom Severity.

BACKGROUND/AIMS: Single swallow integrated relaxation pressure (IRP) on high-resolution manometry (HRM) does not always accurately predict esophagogastric outflow obstruction on timed barium esophagogram (TBE). Furthermore, neither single swallow IRP or TBE is reliable in predicting symptoms, particularly after treatment with dilatation or myotomy. A 200 mL rapid drink challenge (RDC) has been proposed as an adjunctive test during HRM. This serves as a "stress-test" to the esophagogastric junction, and may yield clinically useful parameters. We aim to assess HRM parameters during RDC, and their ability to predict outflow obstruction on TBE in patients with dysphagia, and to correlate with symptoms in patients' achalasia. METHODS: Thirty patients with dysphagia were recruited. All underwent standard single swallow HRM analysis, 200 mL RDC, then TBE. RDC parameters, including esophagogastric pressure gradient, IRP, and RDC duration were evaluated. Multiple regression analysis was performed to assess the best predictive parameter for obstruction on TBE. A further 21 patients with achalasia were evaluated with Eckhardt score, single swallow HRM, RDC, and TBE. Parameter correlation with Eckhardt score was evaluated. RESULTS: Mean IRP during RDC was the best HRM parameter at predicting outflow obstruction on TBE. This performed much better in untreated patients (sensitivity 100% and specificity 85.5%) than in previously treated patients (sensitivity 50% and specificity 66%). In patients with achalasia, mean IRP during RDC was the only parameter that correlated with symptom score. CONCLUSION: Mean IRP during RDC appears to be a clinically useful "stress test" to the esophagogastric junction during HRM.

Superficial Esophageal Mucosal Afferent Nerves May Contribute to Reflux Hypersensitivity in Nonerosive Reflux Disease.

BACKGROUND & AIMS: Little is known about the causes of heartburn in patients with gastro-esophageal reflux disease. Visible epithelial damage is seldom associated with symptom severity, evidenced by the significant symptom burden in patients with nonerosive reflux disease (NERD) compared with patients with erosive reflux disease (ERD) or Barrett's esophagus (BE). We studied the distribution of mucosal nerve fibers in patients with NERD, ERD, and BE, and compared the results with those of healthy subjects. METHODS: We performed a prospective study of 13 patients with NERD, 11 patients with ERD, and 16 patients with BE undergoing endoscopic evaluation in the United Kingdom or Greece. Biopsies were obtained from the proximal and distal esophageal mucosa of patients with NERD, from the distal esophageal mucosa of patients with ERD, and the distal-most squamous epithelium of patients with BE. These were examined for the presence and location of nerve fibers that reacted with a labeled antibody against calcitonin gene-related peptide (CGRP), a marker of nociceptive sensory nerves. The results were compared with those from 10 healthy volunteers (controls). RESULTS: The distribution of CGRP-positive nerves did not differ significantly between the distal esophageal mucosa of controls (median, 25.5 cell layers to surface; interquartile range [IQR], 21.4-28.8) vs patients with ERD (median, 23 cell layers to surface; IQR, 16-27.5), or patients with BE (median, 21.5 cell layers to surface; IQR, 16.1-27.5). However, CGRP-positive nerves were significantly more superficial in mucosa from patients with NERD-both distal (median, 9.5 cell layers to surface; IQR, 1.5-13.3; P < .0001 vs ERD, BE, and controls) and proximal (median, 5.0 cell layers to surface; IQR, 2.5-9.3 vs median 10.4 cell layers to surface; IQR, 8.0-16.9; P = .0098 vs controls). CONCLUSIONS: Proximal and distal esophageal mucosa of patients with NERD have more superficial afferent nerves compared with controls or patients with ERD or BE. Acid hypersensitivity in patients with NERD might be partially explained by the increased proximity of their afferent nerves to the esophageal lumen, and therefore greater exposure to noxious substances in refluxate.

Dedicated Barrett's surveillance sessions managed by trained endoscopists improve dysplasia detection rate.

Background and study aim Barrett's esophagus (BE)-associated dysplasia is an important marker for risk of progression to esophageal adenocarcinoma (EAC) and an indication for endoscopic therapy. However, BE surveillance technique is variable. The aim of this study was to assess the effect of dedicated BE surveillance lists on dysplasia detection rate (DDR). Patients and methods This was a prospective study of patients undergoing BE surveillance at two hospitals - community (UHL) and upper gastrointestinal center (GSTT). Four endoscopists (Group A) were trained in Prague classification, Seattle protocol biopsy technique, and lesion detection prior to performing BE surveillance endoscopies at both sites, with dedicated time slots or lists. The DDR was then compared with historical data from 47 different endoscopists at GSTT and 24 at UHL (Group B) who had undertaken Barrett's surveillance over the preceding 5-year period. Results A total of 729 patients with BE underwent surveillance endoscopy between 2007 and 2012. There was no significant difference in patient age, sex, or length of BE between the two groups. There was a significant difference in detection rate of confirmed indefinite or low grade dysplasia and high grade dysplasia (HGD)/EAC between the two groups: 18 % (26 /142) Group A vs. 8 % (45/587) in Group B (P  < 0.001). Documentation of Prague criteria and adherence to the Seattle protocol was significantly higher in Group A. Conclusion This study demonstrated that a group of trained endoscopists undertaking Barrett's surveillance on dedicated lists had significantly higher DDR than a nonspecialist cohort. These findings support the introduction of dedicated Barrett's surveillance lists.

Chicago Classification of Esophageal Motility Disorders: Applications and Limits in Adults and Pediatric Patients with Esophageal Symptoms.

The Chicago classification (CC) is most valued for its systematic approach to esophageal disorders and great impact in unifying practice for esophageal manometric studies. In view of the ever-growing wealth of knowledge and experience gained by the expanding use of high-resolution manometry (HRM) in various clinical scenarios, the CC is regularly updated. Its clinical impact and ability to predict clinical outcome, both in adults and pediatrics, will be further promoted by recognizing its current limitations, incorporating new metrics in its diagnostic algorithms and adjusting the HRM protocols based on the clinical question posed. Herein, we discuss the current limitations of the CC and highlight some areas of improvement for the future.

Supragastric belching.

PURPOSE OF REVIEW: Supragastric belching has recently gained recognition as a belching disorder of behavioral origin that can be accurately diagnosed on esophageal impedance monitoring. Its contribution to numerous other gastrointestinal disorders is beginning to be appreciated. Improved knowledge of its pathophysiology has enabled identification of therapeutic goals, some of which have been subject to formal study and demonstrated good outcomes. This review sets out to present and discuss new findings related to the improved understanding of the relationship between supragastric belching and other gastrointestinal disorders, as well as fresh concepts in terms of management. RECENT FINDINGS: Supragastric belching is now shown to be associated with globus, as well as reflux symptoms in proton pump inhibitor nonresponders. Patients with supragastric belching experience higher frequency of belching events if they have concurrent esophageal hypomotility. Gum chewing and sleeve gastrectomy have no impact on supragastric belching. Pediatric studies suggest an overlap with aerophagia that is not observed in adults. Successful treatments trialed recently include psychoeducation and behavioral therapy delivered by a health psychologist with expertise in gastroenterology. SUMMARY: With the foreseeable increase in recognition and diagnosis of pathological supragastric belching, there is a clear need to better understand its pathophysiology, especially in terms of its emerging importance in relation to other gastrointestinal disorders. Further study is justified to uncover additional therapeutic options for this benign but disabling condition.

Winner of Young Writer's Competition: How loud is the unquiet mind? William Sargant (1907-88) and British psychiatry in the mid-20th century.

William Walters Sargant (1907-1988) is credited, for better or for worse, with putting physicalist psychiatry on the map--at the expense of the dictum 'primum non nocere' (first do no harm). He was an outspoken supporter and practitioner of what he termed the 'practical rather than philosophical approaches' to the treatment of mental illness. This paper examines Sargant's fascinating career, beginning with the reasons behind lifelong passion for radical psychiatry, then discusses the various physical treatments he pioneered and publicized during his three decades at St Thomas' including prolonged electroconvulsive therapy, insulin coma therapy, dangerous combinations of antidepressants and, most notably, prefrontal leucotomy. His heady mix of dogma and charisma enabled him to get away with flying in the face of evidence-based medicine--but not without courting the considerable controversy and contempt that was to so blacken his reputation posthumously. This paper ends with comments on misguided and misplaced enthusiasm in the history of therapeutics, acknowledgement of Sargant's positive contributions to psychiatry and finally a reminder not to be tempted to pass post hoc judgement on the man or his legacy all too quickly.