An Endoscopic Scoring System for Achalasia: The CARS score.

BACKGROUND AND AIMS: The diagnosis of achalasia is associated with an average delay of two years. Endoscopic features may prompt an earlier diagnosis. We aimed to develop and test a novel endoscopic CARS score for the prediction of achalasia. METHODS: Part 1: Twenty endoscopic videos were taken from patients undergoing endoscopy for dysphagia or reflux. A survey with videos and endoscopic criteria options was distributed to 6 esophagologists and 6 general gastroenterologists. Inter-rater reliability (IRR) was measured and logistic regression was used to evaluate predictive performance. Three rounds of review were conducted to select the final score of four components. PART 2: A retrospective review was conducted for consecutive patients who had comprehensive esophageal testing. Each patient had a CARS endoscopic score calculated based on findings reported at endoscopy. RESULTS: From a video review and analysis of score components, IRR ranged from 0.23 to 0.57 for score components. The final CARS score was selected based on the following four components: Contents, Anatomy, Resistance, and Stasis. In a mixed effects model, the mean score across raters was higher for achalasia compared to non-achalasia subjects (4.44 vs. 0.87, p = < 0.01). In part 2 of the study, achalasia patients had a higher mean CARS score compared to those with no / ineffective motility disorder (mean 4.1 vs 1.3, p = < 0.01). CONCLUSIONS: We developed a CARS score based on reliability performance in a video-based survey and tested the score in clinical setting. The CARS score performed well in predicting achalasia.

A Delphi Method for Development of a Barrett's Esophagus Question Prompt List as a Communication Tool for Optimal Patient-physician Communication.

BACKGROUND METHODS: The question prompt list content was derived through a modified Delphi process consisting of 3 rounds. In round 1, experts provided 5 answers to the prompts "What general questions should patients ask when given a new diagnosis of Barrett's esophagus" and "What questions do I not hear patients asking, but given my expertise, I believe they should be asking?" Questions were reviewed and categorized into themes. In round 2, experts rated questions on a 5-point Likert scale. In round 3, experts rerated questions modified or reduced after the previous rounds. Only questions rated as "essential" or "important" were included in Barrett's esophagus question prompt list (BE-QPL). To improve usability, questions were reduced to minimize redundancy and simplified to use language at an eighth-grade level (Fig. 1). RESULTS: Twenty-one esophageal medical and surgical experts participated in both rounds (91% males; median age 52 years). The expert panel comprised of 33% esophagologists, 24% foregut surgeons, and 24% advanced endoscopists, with a median of 15 years in clinical practice. Most (81%), worked in an academic tertiary referral hospital. In this 3-round Delphi technique, 220 questions were proposed in round 1, 122 (55.5%) were accepted into the BE-QPL and reduced down to 76 questions (round 2), and 67 questions (round 3). These 67 questions reached a Flesch Reading Ease of 68.8, interpreted as easily understood by 13 to 15 years olds. CONCLUSIONS: With multidisciplinary input, we have developed a physician-derived BE-QPL to optimize patient-physician communication. Future directions will seek patient feedback to distill the questions further to a smaller number and then assess their usability.

Frequent discrepancies among diagnostic tests for detecting lower esophageal sphincter-related obstruction.

BACKGROUND: There are frequent discrepancies among high-resolution manometry (HRM), functional lumen imaging probe (FLIP), and esophagram in identifying lower esophageal sphincter (LES)-related obstruction. We aimed to determine the frequency of those discrepancies and how they influenced clinical treatment/outcomes. METHODS: We identified patients who had all three tests (HRM, FLIP, and esophagram) and endoscopy performed for evaluation of esophageal symptoms in our Center for Esophageal Diseases. Discrepancies among the tests for the presence of LES obstruction were noted, and the performance of individual tests was compared against a consensus opinion rendered by a panel of esophagologists. Binary logistical regression was performed, and ROC curves were generated for prediction of the consensus clinical diagnosis of LES obstruction. KEY RESULTS: A total of 126 patients (mean age 57.9 ± 17.0 years; 67% female) met inclusion criteria. All three tests agreed on the presence or absence of LES obstruction in only 72 (57%) patients [no LES obstruction in 57 (45%), LES obstruction in 15 (12%)]. Thirteen patients (10%) had a change in management based on additional findings on FLIP +/- esophagram not seen on HRM with 69% having symptomatic improvement after LES-directed intervention. FLIP was the strongest predictor of a consensus diagnosis of LES obstruction by logistic regression and ROC (OR 23.36, AUC 0.796), followed by HRM (OR 15.41, AUC 0.764). CONCLUSIONS & INFERENCE: High-resolution manometry, functional lumen imaging probe, and esophagram each have considerable limitations for identifying LES obstruction, and discrepancies among these tests occur frequently. Multimodal testing is often required for adequate evaluation of LES-related obstruction.

Gastric Ectopic Pancreas With Pseudocyst Formation Causing Gastric Outlet Obstruction.

Ectopic pancreas is a rare entity referring to the presence of pancreatic tissue at an anatomic location distinct from the pancreas. Ectopic pancreatic lesions in the stomach present a diagnostic challenge because the lack of distinguishing imaging and endoscopic features make them difficult to differentiate from other types of submucosal lesions. We report a case of ectopic pancreas presenting as a gastric antral mass with a unique combination of rare complications: chronic pancreatitis and pseudocyst formation causing gastric outlet obstruction. This case highlights complications that can occur from ectopic pancreatic lesions and the challenges of diagnosing ectopic pancreas.

The broad impact of functional lumen imaging probe panometry in addition to high-resolution manometry in an esophageal clinical practice.

High-resolution manometry (HRM) with the Chicago Classification (CC) is the standard paradigm to define esophageal motility disorders. Functional lumen imaging probe (FLIP) panometry utilizes impedance planimetry to characterize esophageal compliance and secondary peristalsis. The aim of this study was to explore the clinical impact of FLIP panometry in addition to HRM. A retrospective chart review was performed on FLIP panometry cases utilizing the 322N catheter. Cases with prior foregut surgeries or botulinum injection within 6 months of FLIP panometry were excluded. EGJ-diameter and distensibility index (DI) and secondary contraction patterns at increasing balloon volumes were recorded. An EGJ-DI of ≥2.8 mm2/mm Hg at 60 mL was considered as a normal EGJ distensibility. CC diagnosis, Eckhardt score, Brief Esophageal Dysphagia Questionnaire, and clinical outcomes were obtained for each FLIP case. A total of 186 cases were included. Absent contractility and achalasia types 1 and 2 showed predominantly absent secondary contraction patterns, while type 3 had a variety of secondary contractile patterns on FLIP panometry. Among 77 cases with EGJ outflow obstruction (EGJOO), 60% had a low EGJ-DI. Among those with no motility disorder or ineffective esophageal motility on HRM, 27% had a low DI and 47% had sustained contractions on FLIP, raising concern for an esophageal dysmotility process along the achalasia and/or spastic spectrum. FLIP panometry often confirmed findings on HRM in achalasia and absent contractility. FLIP panometry is useful in characterizing EGJOO cases. Spastic features on FLIP panometry may raise concern for a motility disorder on the spastic spectrum not captured by HRM. Further studies are needed on FLIP panometry to determine how to proceed with discrepancy with HRM and explore diagnoses beyond the CC.

Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy Consensus Conference.

Endoscopy plays a critical role in caring for and evaluating the patient with eosinophilic esophagitis (EoE). Endoscopy is essential for diagnosis, assessment of response to therapy, treatment of esophageal strictures, and ongoing monitoring of patients in histologic remission. To date, less-invasive testing for identifying or grading EoE severity has not been established, whereas diagnostic endoscopy as integral to both remains the criterion standard. Therapeutic endoscopy in patients with adverse events of EoE may also be required. In particular, dilation may be essential to treat and attenuate progression of the disease in select patients to minimize further fibrosis and stricture formation. Using a modified Delphi consensus process, a group of 20 expert clinicians and investigators in EoE were assembled to provide guidance for the use of endoscopy in EoE. Through an iterative process, the group achieved consensus on 20 statements yielding comprehensive advice on tissue-sampling standards, gross assessment of disease activity, use and performance of endoscopic dilation, and monitoring of disease, despite an absence of high-quality evidence. Key areas of controversy were identified when discussions yielded an inability to reach agreement on the merit of a statement. We expect that with ongoing research, higher-quality evidence will be obtained to enable creation of a guideline for these issues. We further anticipate that forthcoming expert-generated and agreed-on statements will provide valuable practice advice on the role and use of endoscopy in patients with EoE.

Spastic secondary contractile patterns identified by FLIP panometry in symptomatic patients with unremarkable high-resolution manometry.

BACKGROUND: Functional lumen imaging probe (FLIP) panometry can show spastic secondary contractile patterns of unclear significance in symptomatic patients who have no esophageal obstructive disorders, and no motility disorders on high-resolution manometry (HRM). METHODS: We retrospectively analyzed non-obstructed, symptomatic patients with HRM findings of no motility disorder or ineffective esophageal motility (IEM) for whom spastic secondary contractile patterns identified by FLIP panometry were used to guide treatment. Symptoms were scored using the Brief Esophageal Dysphagia Questionnaire (BEDQ). KEY RESULTS: We identified ten symptomatic patients treated at our medical center who met inclusion criteria (seven women; mean age 56 years; eight no motility disorder, two IEM). On FLIP panometry, seven had spastic secondary contractions at 60 ml, two at 40 ml, and one at both 40 ml and 60 ml balloon volumes. Eight patients (80%) had improvement in BEDQ scores with therapies that targeted the spastic secondary contractile patterns identified by FLIP (five botulinum toxin injection, two Esoflip dilation, and one Heller myotomy). Interestingly, review of HRM tracings revealed that all patients had a novel HRM finding of mid-vertical pressurization in at least 20% swallows, with seven exhibiting this finding in >50% of swallows. CONCLUSIONS: This case series demonstrates that treatments targeting spastic secondary contractions identified by FLIP panometry can result in symptomatic improvement in patients with no obstructive disorder and no diagnostic motility disorder on HRM. In such patients, we have identified the novel HRM finding of mid-vertical pressurization, which might be the manometric manifestation of spasm limited to the mid-esophagus.

Advanced Imaging and Sampling in Barrett's Esophagus: Artificial Intelligence to the Rescue?

Because the current Barrett's esophagus (BE) surveillance protocol suffers from sampling error of random biopsies and a high miss-rate of early neoplastic lesions, many new endoscopic imaging and sampling techniques have been developed. None of these techniques, however, have significantly increased the diagnostic yield of BE neoplasia. In fact, these techniques have led to an increase in the amount of visible information, yet endoscopists and pathologists inevitably suffer from variations in intra- and interobserver agreement. Artificial intelligence systems have the potential to overcome these endoscopist-dependent limitations.

Prospective development and validation of a volumetric laser endomicroscopy computer algorithm for detection of Barrett's neoplasia.

BACKGROUND AND AIMS: Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used to detect Barrett's esophagus (BE) dysplasia. However, real-time interpretation of VLE scans is complex and time-consuming. Computer-aided detection (CAD) may help in the process of VLE image interpretation. Our aim was to train and validate a CAD algorithm for VLE-based detection of BE neoplasia. METHODS: The multicenter, VLE PREDICT study, prospectively enrolled 47 patients with BE. In total, 229 nondysplastic BE and 89 neoplastic (high-grade dysplasia/esophageal adenocarcinoma) targets were laser marked under VLE guidance and subsequently underwent a biopsy for histologic diagnosis. Deep convolutional neural networks were used to construct a CAD algorithm for differentiation between nondysplastic and neoplastic BE tissue. The CAD algorithm was trained on a set consisting of the first 22 patients (134 nondysplastic BE and 38 neoplastic targets) and validated on a separate test set from patients 23 to 47 (95 nondysplastic BE and 51 neoplastic targets). The performance of the algorithm was benchmarked against the performance of 10 VLE experts. RESULTS: Using the training set to construct the algorithm resulted in an accuracy of 92%, sensitivity of 95%, and specificity of 92%. When performance was assessed on the test set, accuracy, sensitivity, and specificity were 85%, 91%, and 82%, respectively. The algorithm outperformed all 10 VLE experts, who demonstrated an overall accuracy of 77%, sensitivity of 70%, and specificity of 81%. CONCLUSIONS: We developed, validated, and benchmarked a VLE CAD algorithm for detection of BE neoplasia using prospectively collected and biopsy-correlated VLE targets. The algorithm detected neoplasia with high accuracy and outperformed 10 VLE experts. (The Netherlands National Trials Registry (NTR) number: NTR 6728.).

Advances in endoscopy for colorectal polyp detection and classification.

While colonoscopy is considered the gold standard for colon cancer screening, recent advancements in endoscopes have allowed for improved visualization of the colonic mucosa and improved polyp detection rates. Newer technologies also allow for assessment of structural changes for polyp discrimination and determination of histologic type. Classification of polyps prevents the need for a histopathologic report, which requires the additional time and expertise of a pathologist and adds to the overall cost. This review considered advances in endoscopic technologies reported in PubMed over the past 12 years. Technologies that allow for increased visual field of colonic mucosa and may lead to improved colon polyp detection rates include cap-assisted colonoscopy, RetroView, extra-wide-angle view colonoscope, full-spectrum endoscopy, Third Eye Retroscope, NaviAid G-EYE balloon colonoscope, EndoRings, and Endocuff. Image-enhancing methods allow for pit pattern analysis of colorectal lesions, which enables the physician to classify colorectal polyps according to certain polyp characteristics. Image-enhancing methods include chromoendoscopy, autofluorescence, and virtual chromoendoscopy, including narrow band imaging, i-SCAN, flexible spectral imaging chromoendoscopy, and STORZ professional image enhancement systems. In addition, advancements have been made in in vivo microscopic evaluation of colonic epithelium, including confocal laser endomicroscopy, endocytoscopy, optical coherence tomography, spectroscopy, and autofluorescence spectroscopy. Colon capsule endoscopy also has a role in colon polyp detection and classification. The advancements in polyp detection and classification have great promise for earlier detection and removal of advanced adenomas before they advance to colorectal cancer.

Barrett's Esophagus and Esophageal Carcinoma: Can Biomarkers Guide Clinical Practice?

PURPOSE OF REVIEW: Despite gastrointestinal societal recommendations for endoscopic screening and surveillance of Barrett's esophagus, the rates of esophageal adenocarcinoma continue to rise. Furthermore, this current practice is costly to patients and the medical system without clear evidence of reduction in cancer mortality. The use of biomarkers to guide screening, surveillance, and treatment strategies might alleviate some of these issues. RECENT FINDINGS: Incredible advances in biomarker identification, biomarker assays, and minimally-invasive modalities to acquire biomarkers have shown promising results. We will highlight recently published, key studies demonstrating where we are with using biomarkers for screening and surveillance in clinical practice, and what is on the horizon regarding novel non-invasive and minimally invasive methods to acquire biomarkers. Proof-of principle studies using in silico models demonstrate that biomarker-guided screening, surveillance, and therapeutic intervention strategies can be cost-effective and can reduce cancer deaths in patients with Barrett's esophagus.

Aberrant p53 Immunostaining in Barrett's Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses.

Risk stratification of patients with Barrett's esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p < .001 (95% CI 2.79-5.27) and OR 5.95, p < .001 (95% CI 2.68-13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p < .001 (95% CI 9.35-32.08) and RR = 14.25, p < .001 (95% CI 6.76-30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.

Biomarkers of Barrett's Esophagus: From the Laboratory to Clinical Practice.

The currently recommended approach to managing cancer risk for patients with Barrett's esophagus is endoscopic surveillance including a biopsy protocol to sample the esophageal tissue randomly to detect dysplasia. However, there are numerous limitations in this practice that rely on the histopathological grading of dysplasia alone to make clinical decisions. The availability of in silico models demonstrating the potential cost-effectiveness of biomarker-based stratification has increased interest in finding a clinically relevant "Barrett's biomarker." The success of endoscopic eradication therapy in preventing neoplastic progression of dysplastic Barrett's esophagus has promoted the desire to stratify non-dysplastic Barrett's esophagus to those with "high risk" that may benefit from endotherapy. Furthermore, on the other end of the spectrum, there is interest in searching for a "low risk" marker that may identify those that would not likely benefit from endoscopy screening or surveillance. This review highlights recent data from the genomics (r)evolution revealing new genetic biomarkers of susceptibility to the development of Barrett's esophagus and novel pathways for its neoplastic progression, addresses the development of new modes of tissue sampling and imaging to detect early neoplasia in Barrett's esophagus, and discusses current progress in moving biomarkers from the laboratory into clinical practice in the era of precision medicine.

Efficacy, Durability, and Safety of Complete Endoscopic Mucosal Resection of Barrett Esophagus: A Systematic Review and Meta-Analysis.

GOALS: To report the rate of eradication and recurrence of both neoplasia and intestinal mucosa and the rate of adverse events for complete endoscopic resection (CER) of Barrett esophagus (BE). BACKGROUND: There is limited composite data on the clinical efficacy of CER of BE with high-grade dysplasia or neoplasia. STUDY: We performed a systematic review and meta-analysis of cohort studies that reported the clinical outcome of patients with BE who underwent CER and had at least 15-month follow-up after the time of elimination of BE. Main outcome of interests were pooled estimated rates of complete eradication of intestinal metaplasia and neoplasia, recurrence of intestinal metaplasia and neoplasia, and incidence of esophageal stricture, bleeding, and perforation. RESULTS: We identified 8 studies reporting on 676 patients (high-grade dysplasia 54%) that met our criteria. Pooled estimated rates of complete eradication of intestinal metaplasia and complete eradication of intestinal neoplasia were 85.0% [95% confidence interval (CI), 79.4%-89.2%] and 96.6% (95% CI, 94.0%-98.1%), respectively, and rates of recurrence of intestinal metaplasia and recurrence of intestinal neoplasia were 15.7% (95% CI, 8.0%-28.4%) and 5.8% (95% CI, 3.9%-8.6%), respectively. Estimated incidences of adverse events were stricture 37.4 (95% CI, 24.4%-52.6%), bleeding 7.9% (95% CI, 4.4%-13.8%) and perforation 2.3% (95% CI, 1.3%-4.1%). CONCLUSIONS: CER achieves an 85% complete eradication rate of BE with recurrent rate of neoplasia of 6%. Estimated rate of postprocedural stricture was 37.4%. On the basis of this high rate of adverse events and significant heterogeneity in the studies included, the present meta-analysis cannot endorse CER as sole therapy for BE.

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.

Importance of Esophageal Manometry and pH Monitoring in the Evaluation of Patients with Refractory Gastroesophageal Reflux Disease: A Multicenter Study.

BACKGROUND: Patients who have heartburn are treated with acid-reducing medications on the assumption that gastroesophageal reflux disease (GERD) is causing the symptom. In the absence of a response to therapy, patients are often assumed to have refractory GERD, and they are referred for laparoscopic antireflux surgery (LARS), often without further diagnostic evaluation. HYPOTHESIS: We hypothesized that (1) in some patients with refractory GERD, the heartburn is not secondary to reflux, but rather to stasis and fermentation of food in the presence of achalasia and (2) esophageal manometry and pH monitoring are essential to establish proper diagnosis. PATIENTS AND METHODS: Five hundred twenty-four patients, whose final diagnosis was achalasia, were referred to two quaternary care centers. Symptomatic evaluation, barium swallow, endoscopy, manometry, and pH monitoring were performed in all patients. RESULTS: One hundred fifty-two patients (29%) had been treated with acid-reducing medications for an average of 29.3 months, and were referred for LARS because of lack of response to medical therapy. One patient had already been treated with a Nissen fundoplication. All patients were diagnosed with achalasia and underwent Heller myotomy and partial fundoplication. CONCLUSIONS: The results of this study showed that (1) one-third of achalasia patients complained of heartburn and (2) patients with heartburn not responding to medical treatment must be carefully evaluated before referral to surgery. These data confirm the importance of esophageal manometry and pH monitoring in any patient considered for LARS.