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.

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.

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.).

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.

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.

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.

Risk of infection transmission in curvilinear array echoendoscopes: results of a prospective reprocessing and culture registry.

BACKGROUND AND AIMS: The complex design of the elevator mechanism in duodenoscopes has been recognized as a challenge for disinfection and recently implicated as a potential source of persistent bacterial contamination. Curvilinear array (CLA) echoendoscopes also have an elevator mechanism; however, there are no recommendations or data regarding the risk of persistent bacterial contamination of echoendoscopes. Here we hoped to determine the yield of microbial growth with routine bacterial surveillance cultures of reprocessed CLA echoendoscopes. METHODS: Beginning in February 2015 to February 2016, CLA echoendoscopes at a single tertiary care center underwent prospective bacterial surveillance cultures after reprocessing. Any growth of gram-negative bacilli was considered to be critical. Echoendoscopes with a positive result underwent quarantine followed by repeat disinfection and culture. RESULTS: During the study period, 540 cultures were obtained; 521 (96.5%) were primary cultures obtained from 18 CLA echoendoscopes. Twenty-two primary cultures (4.2%) were positive for gram-negative bacilli after high-level disinfection reprocessing. Eleven different bacteria were isolated: Klebsiella pneumoniae, Citrobacter freundii, Escherichia coli, Pseudomonas aeruginosa, Klebsiella oxytoca, Sphingomonas paucimobilis, Acinetobacter baumanii, Enterobacter cloacae, Hafnia alvei, Pseudomonas putida, and Stenotrophomonas maltophilia. Antibiotic sensitivity data on 19 of 24 bacteria (79.2%) isolated from positive primary cultures revealed no documented cases of carbapenem-resistant enterobacteriaceae, cephalosporin-resistant-Klebsiella, or multidrug-resistant Acinetobacter. There have been no documented cases of patient-to-patient transmission. CONCLUSIONS: After following standard high-level disinfection and reprocessing, CLA echoendoscopes can remain culture positive for high-concern organisms. Recommendations regarding infection risk should take into consideration elevator-containing echoendoscopes in addition to duodenoscopes to ensure patient safety and endoscope reprocessing efficacy.

Acquisition of Portal Venous Circulating Tumor Cells From Patients With Pancreaticobiliary Cancers by Endoscopic Ultrasound.

BACKGROUND & AIMS: Tumor cells circulate in low numbers in peripheral blood; their detection is used predominantly in metastatic disease. We evaluated the feasibility and safety of sampling portal venous blood via endoscopic ultrasound (EUS) to count portal venous circulating tumor cells (CTCs), compared with paired peripheral CTCs, in patients with pancreaticobiliary cancers (PBCs). METHODS: In a single-center cohort study, we evaluated 18 patients with suspected PBCs. Under EUS guidance, a 19-gauge EUS fine needle was advanced transhepatically into the portal vein and as many as four 7.5-mL aliquots of blood were aspirated. Paired peripheral blood samples were obtained. Epithelial-derived CTCs were sorted magnetically based on expression of epithelial cell adhesion molecules; only those with a proper morphology and found to be CD45 negative and positive for cytokeratins 8, 18, and/or 19 and 4',6-diamidino-2-phenylindole were considered to be CTCs. For 5 samples, CTCs also were isolated by flow cytometry and based on CD45 depletion. ImageStream was used to determine the relative protein levels of P16, SMAD4, and P53. DNA was extracted from CTCs for sequencing of select KRAS codons. RESULTS: There were no complications from portal vein blood acquisition. We detected CTCs in portal vein samples from all 18 patients (100%) vs peripheral blood samples from only 4 patients (22.2%). Patients with confirmed PBCs had a mean of 118.4 ± 36.8 CTCs/7.5 mL portal vein blood, compared with a mean of 0.8 ± 0.4 CTCs/7.5 mL peripheral blood (P < .01). The 9 patients with nonmetastatic, resectable, or borderline-resectable PBCs had a mean of 83.2 CTCs/7.5 mL portal vein blood (median, 62.0 CTCs/7.5 mL portal vein blood). In a selected patient, portal vein CTCs were found to carry the same mutations as those detected in a metastatic lymph node and expressed similar levels of P16, SMAD4, and P53 proteins. CONCLUSIONS: It is feasible and safe to collect portal venous blood from patients undergoing EUS. We identified CTCs in all portal vein blood samples from patients with PBCs, but less than 25% of peripheral blood samples. Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue. This technique might be used to study the pathogenesis and progression of PBCs, as well as a diagnostic or prognostic tool to stratify risk of cancer recurrence or developing metastases.

Safety and efficacy of EMR for sporadic, nonampullary duodenal adenomas: a single U.S. center experience (with video).

BACKGROUND AND AIMS: EMR is increasingly used for resection of sporadic, nonampullary duodenal adenomas (SNDAs), but there are no guidelines for the management of these lesions. The aims of this study were to evaluate the safety and efficacy of EMR exclusively for SNDAs and to determine the factors predictive of outcomes. METHODS: We performed a retrospective review of patients with SNDAs referred for endoscopic therapy from 2006 to 2013. The outcomes studied were successful endoscopic resection, major adverse events, early and late recurrences, and clinical remission. RESULTS: Sixty-eight patients with SNDAs were included and 51 (75%) underwent EMR. The mean adenoma size was 22.0 ± 8.9 mm. Successful resection was achieved in 49 of 51 patients (96.1%), and major adverse events were noted in 8 of 51 patients (15.7%). Early and late recurrences were noted in 25.6% and 5.2% of patients, respectively, and were treated endoscopically. Clinical remission was achieved in 89.7% of patients after a median follow-up of 15 months. Presence of villous histology was associated with increased recurrence (P = .019), but no association of recurrence was noted with other endoscopic features or resection technique. Large adenoma size (P = .0057) and need for intraprocedural hemostasis (P = .006) were associated with increased adverse events, but no association of adverse events was noted with location or resection technique. CONCLUSIONS: Large duodenal adenomas can be effectively managed with EMR at a referral center with experienced endoscopists. However, EMR has a significant recurrence rate, especially early recurrence, and the risk of adverse events is not negligible. Endoscopic therapy is successful in managing recurrent adenomas.

Needle-based confocal endomicroscopy for pancreatic cysts: the current agreement in interpretation.

BACKGROUND AND AIMS: Diagnosis of pancreatic cystic lesions (PCLs) remains challenging. EUS with FNA is limited by sampling error and nondiagnostic cytology. Needle-based confocal laser endomicroscopy (nCLE) performed during EUS can be used to improve diagnostic yield via FNA by providing in vivo histology of PCLs. However, the interobserver agreement (IOA) of nCLE of PCLs has yet to be studied. METHODS: Fifteen deidentified nCLE video clips of PCLs were sent to 6 interventional endoscopists at 5 institutions. Six variables were assessed for IOA: presence or absence of (1) vessels, (2) villi, (3) dark clumps, (4) reticular pattern, (5) acinar cells pattern, and (6) debris. PCL interpretation was categorized as mucinous, serous, pseudocyst, malignant, or indeterminate and final diagnosis as benign, malignant, or indeterminate. RESULTS: IOA ranged from "poor" to "fair." The K statistics were -.04 (SE = .05) for vessels, .16 (SE = .07) for villi, .22 (SE = .06) for dark clumps, .13 (SE = .06) for reticular pattern, .14 (SE = .06) for acinar cells pattern, .06 (SE = .06) for debris, .15 (SE = .03) for interpretation, .13 (SE = .05) for final diagnosis, and .19 (SE = .05) for image quality. The final diagnosis was malignant (10), benign (13), and indeterminate (2). The mean accuracy of the observers was 46%, with the lowest being 20% and highest being 67%. CONCLUSIONS: The IOA and accuracy for PCL diagnosis were low. The results of this study support the need to identify and validate imaging criteria to determine whether nCLE has diagnostic value for pancreatic pathology. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02166086.).

A single-center experience of endoscopic submucosal dissection performed in a Western setting.

BACKGROUND: Compared with the piecemeal resection associated with endoscopic mucosal resection, endoscopic submucosal dissection (ESD) enables en bloc resection of larger lesions, allows for more accurate histological assessments, and has reduced recurrence rates. ESD is not widely performed in Western countries given increased technical difficulty, high complication rates, and long procedure times. AIMS: To evaluate the safety and efficacy of ESD in a single center in the USA. METHODS: A retrospective study on a prospectively collected database identified cases in which a single operator (IW) performed ESD at a tertiary referral center. Twenty cases were identified, nine in the upper digestive tract (four esophagus and five stomach) and 11 in the lower digestive tract (nine rectal and two sigmoid colon). Data regarding lesion location, pathology, method of ESD (composition/volume of lifting injection and resection method), post-procedure complications, and margin involvement were collected. RESULTS: En bloc resection was obtained in 14/20 patients (70 %). The average procedure time was 202 min in the esophagus, 148 min in the stomach, and 106 min for lower lesions. A major complication (perforation) occurred in 1/20 cases (5 %). Complete resection was obtained in 14/20 (70 %). R0 resection was obtained in 16/20 (80 %) cases. CONCLUSIONS: The complication, en bloc resection, and complete resection rates of this study are similar to those found in large studies on ESD performed in Eastern settings. ESD is safe and efficacious for en bloc resections of pre-malignant and early-invasive lesions, and should be offered to patients with suitable lesions in Western settings.

Complete endoscopic mucosal resection is effective and durable treatment for Barrett's-associated neoplasia.

BACKGROUND & AIMS: Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal carcinoma (IMC) is treated by complete eradication of areas of BE by endoscopic mucosal resection (EMR). By using this approach, histologic analysis also can be performed. We investigated the effectiveness, safety, and durability of this approach, as well as its use in diagnosis after a single referral. METHODS: We collected data from 107 patients who were referred to the Center for Endoscopic Research and Therapeutics at the University of Chicago for BE (mean length, 3.6 cm) with suspected HGD or IMC, from August 2003 through December 2012. All patients underwent EMR and were followed up through January 2014 (mean follow-up time, 40.6 mo). The primary outcome was treatment efficacy (complete eradication of BE and associated neoplasia); secondary outcomes included safety, durability, and accuracy of diagnosis. RESULTS: BE was eradicated completely by EMR in 80.4% (86 of 107) of patients based on intention-to-treat analysis, and in 98.8% (79 of 80) of patients based on per-protocol analysis. The diagnosis was changed for 25% of patients after EMR, including 4 cases that initially were diagnosed as HGD by biopsy analysis and subsequently were found to have evidence of submucosal invasion when EMR specimens were assessed. Strictures and symptomatic dysphagia developed in 41.1% and 37.3% of patients, respectively, with an average of 2.3 dilations required. Perforations occurred in 2 patients after EMR and in 1 patient after dilation. HGD and IMC recurred in 1 patient each; both were treated successfully with EMR. Based on pathology analysis of the most recently collected specimens, 71.6% of patients (53 of 74) were in complete remission from intestinal metaplasia and 100% were in complete remission from HGD (74 of 74) or cancer (74 of 74). CONCLUSIONS: For patients with BE with HGD or neoplasia, complete EMR is an effective and durable treatment and is a relatively safe technique. Specimens collected by EMR also can be analyzed histologically to aid in diagnosis. The common complication of EMR is esophageal stricture, which can be addressed with endoscopic dilation.

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.

Evaluation of microvascular density in Barrett's associated neoplasia.

Angiogenesis has an important role in the carcinogenesis of esophageal adenocarcinoma, however, the diagnostic and prognostic utility of microvascular density counts have not been clinically established. The aim of this study is to assess the correlation between microvascular density and disease progression of non-dysplastic Barrett's esophagus, low-grade dysplasia, high-grade dysplasia and invasive carcinoma in the superficial aspects of the tissue. Archival histological specimens from two referral centers for Barrett's esophagus and esophageal cancer were selected for review. A total of 160 regions marked according to histological grade were assessed with digitally interactive software to measure microvascular density. This was quantified in three levels: 0-50, 50-100 and 100-150 µm. In the areas of gastric cardia, Barrett's esophagus, low-grade dysplasia, high-grade dysplasia and cancer, microvascular density was significantly different (P<0.0001) among the five groups in the most superficial 150 µm of the mucosa. Furthermore, when examining the pairwise difference between the groups, there was a significant difference between cancer and each of the lower grades of histology (P<0.05) and between high-grade dysplasia and each of the lower grades of histology (P<0.05). These statistically significant differences were preserved in examining the depth at the most superficial 50 µm. We have used digital pathology to demonstrate a significant and stepwise increase in microvascular density, which supports the hypothesis that angiogenesis has a key role in Barrett's carcinogenesis. Furthermore, the differences in the most superficial mucosal layers are consistent with findings of increased vascularity by depth-restricted imaging modalities.

Nanoscale markers of esophageal field carcinogenesis: potential implications for esophageal cancer screening.

BACKGROUND AND STUDY AIMS: Esophageal adenocarcinoma (EAC) has a dismal prognosis unless treated early or prevented at the precursor stage of Barrett's esophagus-associated dysplasia. However, some patients with cancer or dysplastic Barrett's esophagus (DBE) may not be captured by current screening and surveillance programs. Additional screening techniques are needed to determine who would benefit from endoscopic screening or surveillance. Partial wave spectroscopy (PWS) microscopy (also known as nanocytology) measures the disorder strength (Ld ), a statistic that characterizes the spatial distribution of the intracellular mass at the nanoscale level and thus provides insights into the cell nanoscale architecture beyond that which is revealed by conventional microscopy. The aim of the present study was to compare the disorder strength measured by PWS in normal squamous epithelium in the proximal esophagus to determine whether nanoscale architectural differences are detectable in the field area of EAC and Barrett's esophagus. METHODS: During endoscopy, proximal esophageal squamous cells were obtained by brushings and were fixed in alcohol and stained with standard hematoxylin and Cyto-Stain. The disorder strength of these sampled squamous cells was determined by PWS. RESULTS: A total of 75 patient samples were analyzed, 15 of which were pathologically confirmed as EAC, 13 were DBE, and 15 were non-dysplastic Barrett's esophagus; 32 of the patients, most of whom had reflux symptoms, acted as controls. The mean disorder strength per patient in cytologically normal squamous cells in the proximal esophagus of patients with EAC was 1.79-times higher than that of controls (P<0.01). Patients with DBE also had a disorder strength 1.63-times higher than controls (P<0.01). CONCLUSION: Intracellular nanoarchitectural changes were found in the proximal squamous epithelium in patients harboring distal EAC and DBE using PWS. Advances in this technology and the biological phenomenon of the field effect of carcinogenesis revealed in this study may lead to a useful tool in non-invasive screening practices in DBE and EAC.