Lipham, John C.

Goals: A systematic review and meta-analysis of published clinical validity studies was conducted to evaluate the predictive performance of the TSP-9 test. Background: Identifying patients with Barrett’s esophagus (BE) who will progress to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) is challenging. The tissue systems pathology (TSP-9) test can predict risk of progression to HGD/EAC in BE patients. Study: Databases were searched for studies that assessed the clinical validity of TSP-9, and data describing progressors, non-progressors, TSP-9 results, and hazard ratios (HR) with 95% confidence intervals (CIs) were extracted. Odds ratios (OR), sensitivity, specificity, and prevalence-adjusted positive and negative predictive values (PPV adj /NPV adj ) were calculated and used for meta-analysis. Results: Six studies met eligibility criteria, comprising 699 patients. ORs and HRs for TSP-9 had mean common effect size estimates of 6.52 (95% CI: 4.40-9.66, P <0.0001, I 2 =33%) and 6.66 (95% CI: 4.59-9.66, P <0.0001, I 2 =0%), respectively, for predicting progression to HGD/EAC. Mean common effect size estimates were 61% (95% CI: 54%-68%) for sensitivity, 81% (95% CI: 78%-84%) for specificity, 28% (95% CI: 17%-42%) for PPV adj (high risk), 14% (95% CI: 9%-21%) for PPV adj (high/int risk), and 97% (95% CI: 96%-98%) for NPV adj with minimal inter-study heterogeneity ( I 2 =79%, 21%, 0%, 0%, and 0%, respectively). Conclusions: Effect estimates of TSP-9 performance demonstrate that the test provides risk stratification for BE patients. The TSP-9 test can provide clinically impactful results to enable escalation of care for high-risk patients or to identify low-risk patients who can be safely managed with routine surveillance.

Background: Pathologic reflux is a common debilitating digestive condition and anti-reflux surgery is an effective treatment option. Depending on the specifics of the procedure, anti-reflux surgery leads to distinct changes in the endoscopic appearance of the esophagogastric junction (EGJ). This American Foregut Society (AFS) white paper develops nomenclature for describing the endoscopic characteristics of the EGJ after commonly performed laparoscopic antireflux operations. Methods: The AFS Anti-Reflux Barrier Collaborative analyzed the anatomic manipulation and corresponding endoscopic appearance of the EGJ after commonly performed anti-reflux surgery including: (1) 360° anterior/posterior (AP) fundoplication (Nissen); (2) posterior partial fundoplication (Toupet); (3) anterior partial fundoplication (Watson, Dor); (4) magnetic sphincter augmentation; and (5) concomitant hiatal hernia repair with transoral fundoplication (cTIF). Results: Characteristics common to the anti-reflux surgery procedures include restoration of intra-abdominal esophageal length and crural diaphragm repair such that the hiatal aperture is no longer visible in the retroflexed endoscopic view. With regard to the geometry of anti-reflux procedures, the Collaborative established that when evaluated endoscopically in retroflection, the surgically constructed valve should be described in reference to the angle of His and the extent of anatomic change described in terms of (1) the depth of the anterior and posterior grooves, (2) the apposition of the valve collar to the endoscope, (3) the length of the valve, and (4) the position of the squamocolumnar junction relative to the lip of the valve. Conclusions: Current anti-reflux operations share much in common but employ varying degrees of valvular reconstruction leading to distinct endoscopic characteristics. Developing a consistent nomenclature for describing the appearance of the post-surgical valve is essential to develop a better understanding of how variables such as the tightness of the hiatal repair, tightness of the valve collar, and length of the valve can impact the outcome of anti-reflux surgery and predict reflux recurrence.

Background: Within the spectrum of gastroesophageal reflux disease (GERD), pathologic reflux applies to the subset of patients with either erosive esophagitis or abnormal esophageal acid exposure on pH-metry, consequences of a dysfunctional antireflux barrier (ARB). Methods: The American Foregut Society (AFS) tasked a 13-member working group of expert foregut surgeons and esophagologists (The ARB Cooperative) to develop a white paper on ARB function, dysfunction, and mechanisms of action of antireflux surgery through discussion of relevant literature summarized herein. Results: The ARB Cooperative concluded that pathologic reflux is a consequence of the interplay between progressive anatomical distortion of the ARB and physiology. Factors contributing to ARB dysfunction include (1) separation of crural diaphragm from the lower esophageal sphincter with widening of the hiatus and diminished crural diaphragm sphincteric function; (2) loss of the intra-abdominal lower esophageal sphincter segment with complete disabling of the flap valve component of the ARB; (3) axial hiatal hernia leading to reflux during swallow-induced lower esophageal sphincter (LES) relaxation, LES hypotension, inspiration related reflux, a lowered threshold for eliciting transient LES relaxations, and increased compliance of the gastroesophageal junction leading to greater diameter of sphincter opening during transient LES relaxations. With regard to antireflux surgery, the objectives include: (1) reduction of hiatal hernia and restoration of the intra-abdominal esophageal segment; (2) repair of the dilated hiatus; (3) restoring flap valve function by modifying gastroesophageal anatomy; and (4) restricting gastroesophageal junction opening during periods of relaxation. Conclusions: This ARB Cooperative white paper supports the concept of there being 3 major inter-related mechanisms promoting ARB competence: the LES as an intrinsic sphincter, the crural diaphragm as an extrinsic sphincter, and the gastroesophageal valve, a mechanical 1-way valve. Pathological reflux occurs with progressive anatomical disruption of the ARB which in turn leads to physiological dysfunction, the severity of which parallels the extent of anatomical disruption. The corollary of this is that the primary mechanism of antireflux surgery is to restore the ARB by eliminating or compensating for its anatomical disruption. It is the hope of the cooperative that understanding the proposed framework will help clinicians and researchers in improving antireflux procedures.

Background: The American Foregut Society (AFS) is dedicated to advancing patient care and digestive health within the realm of foregut disease. One of the most common and debilitating esophageal conditions is gastroesophageal reflux disease (GERD). The Hill grade is an endoscopic classification of the esophagogastric junction (EGJ) based on the appearance of the gastroesophageal flap valve from a retroflexed view of the hiatus. This endoscopic classification provides insight into the anatomic disruption of the EGJ which has been shown to correlate with GERD. However, clinical utilization of this classification by endoscopists has been limited due to the perceived relevance and subjectivity of the classification. With the advent of endoscopic treatment options for GERD, there is renewed enthusiasm to develop a grading system of the EGJ that can objectively define anatomical impairment and reduce interobserver grading variability. Methods: The AFS convened a 13-member working group tasked with reviewing the Hill grade classification and formulating a proposal for its revision utilizing a modified Delphi method. This white paper summarizes the output from this working group. Results: The working group concluded that all components of the antireflux barrier—the lower esophageal sphincter and its sling fibers, the crural diaphragm, and the gastroesophageal flap valve—contribute to EGJ integrity. Using defined objective parameters of extent of hiatal axial herniation and crural disruption and presence or absence of a flap valve, the new AFS classification stratifies EGJ integrity from normal (grade 1) to increasing degrees of EGJ disruption (grade 2-4) beginning with loss of the flap valve and progressing to increasing degrees of crural disruption and hiatus hernia. This AFS classification also stipulates appropriate endoscopic methodology to utilize in making the assessment and provides a basic nomenclature for communication among endoscopists. Conclusions: The AFS endoscopic classification of the EGJ expands on the Hill classification by including assessment of axial hiatal hernia length (L), hiatal aperture diameter (D), and presence or absence of the flap valve (F) making it more comprehensive - LDF components. Future directions include validation studies correlating the ability of the AFS classification in predicting the presence and severity of GERD.

SUMMARY Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291