Multicenter, Prospective Trial of Nonendoscopic Biomarker-Driven Detection of Barrett's Esophagus and Esophageal Adenocarcinoma.

INTRODUCTION: Preliminary data suggest that an encapsulated balloon (EsoCheck), coupled with a 2 methylated DNA biomarker panel (EsoGuard), detects Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with high accuracy. The initial assay requires sample freezing upon collection. The purpose of this study was to assess a next-generation EsoCheck sampling device and EsoGuard assay in a much-enlarged multicenter study clinically enhanced by using a Clinical Laboratory Improvement Amendments of 1988-compliant assay and samples maintained at room temperature. METHODS: Cases with nondysplastic BE (NDBE), dysplastic BE (indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia), EAC, junctional adenocarcinoma, plus endoscopy controls without esophageal intestinal metaplasia, were prospectively enrolled. Medical assistants at 6 institutions delivered the encapsulated balloon per orally with inflation in the stomach. The inflated balloon sampled the distal 5 cm of the esophagus and then was deflated and retracted into the capsule, preventing sample contamination. EsoGuard bisulfite sequencing assayed levels of methylated vimentin and methylated cyclin A1. RESULTS: A total of 243 evaluable patients-88 cases (median age 68 years, 78% men, 92% White) and 155 controls (median age 57 years, 41% men, 88% White)-underwent adequate EsoCheck sampling. The mean procedural time was approximately 3 minutes. Cases included 31 with NDBE, 16 with indefinite for dysplasia/low-grade dysplasia, 23 with high-grade dysplasia, and 18 with EAC/junctional adenocarcinoma. Thirty-seven NDBE and dysplastic BE cases (53%) were short-segment BE (<3 cm). Overall sensitivity was 85% (95% confidence interval 0.78-0.93) and specificity was 85% (95% confidence interval 0.79-0.90). Sensitivity for NDBE was 84%. EsoCheck/EsoGuard detected 100% of cancers (n = 18). DISCUSSION: EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.

Liquid nitrogen spray cryotherapy for eradication of dysplastic Barrett's esophagus: results from a multicenter prospective registry.

BACKGROUND AND AIMS: Liquid nitrogen spray cryotherapy (SCT) is an alternative to radiofrequency ablation (RFA) for eradication of dysplastic Barrett's esophagus (BE). We aimed to assess the safety, efficacy, and durability of SCT in a multicenter U.S. registry. METHODS: This is a multicenter prospective registry of adults with BE treated with truFreeze Spray Cryotherapy (Steris, Mentor, Ohio, USA) (4 community and 11 academic sites, 2013-2022). Complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) were assessed in BE with dysplasia or intramucosal adenocarcinoma. Kaplan-Meier analysis of CEIM and CED was performed. Hazard ratios for CEIM stratified by baseline risk factors were calculated. RESULTS: Among 138 subjects with low-grade dysplasia (24%), high-grade dysplasia (49%), and intramucosal adenocarcinoma (27%), 34% received prior RFA therapy. Subjects received a median of 2 SCT sessions. Adverse events were uncommon, with 5.5% reporting strictures and 0.7% a perforation. Rates of CEIM and CED, respectively, were 66% and 84% after 2 years and 67% and 92% after 3 years. In RFA-naive patients, CEIM was 77% and CED was 96% at 3 years. Increasing BE length (per centimeter: adjusted hazard ratio, 0.90; 95% confidence interval, 0.83-0.96) and prior treatment with RFA (adjusted hazard ratio, 0.39; 95% confidence interval, 0.22-0.69) were associated with a lower rate of CEIM. Recurrence occurred in 8.8% (n = 6) at a mean follow-up of 2.5 years after CEIM. CONCLUSION: In this largest reported prospective cohort, liquid nitrogen SCT was safe and effective for the treatment of dysplastic and neoplastic BE. Response was lower in those with prior failed RFA; in that cohort, approximately 50% attained CEIM at 3 years.

Patients With Esophageal Adenocarcinoma With Prior Gastroesophageal Reflux Disease Symptoms Are Similar to Those Without Gastroesophageal Reflux Disease: A Cross-Sectional Study.

INTRODUCTION: A substantial proportion of patients with esophageal adenocarcinoma (EAC) do not report gastroesophageal reflux disease (GERD) symptoms. This study aimed to compare the risk factor profiles and cancer stage at presentation of patients with EAC with and without prior GERD. METHODS: In this retrospective cross-sectional study, patients with EAC were divided into 2 cohorts: (i) EAC with prior GERD: patients who reported typical GERD symptoms (heartburn or regurgitation) ≥1 year before cancer diagnosis and (ii) EAC without prior GERD: patients who did not report prior GERD symptoms or reported symptoms within 1 year of their cancer diagnosis. Baseline demographics, risk factors, and cancer stage at presentation were compared between the 2 cohorts. In addition, the distribution of patients based on numbers of BE/EAC-associated risk factors (1, 2, 3, 4, and 5 or more) was examined in the symptomatic and asymptomatic cohorts. RESULTS: Over 13 years, 388 patients with EAC with prior GERD and 245 patients with EAC without prior GERD were recruited. Both groups had similar baseline demographics and risk factors, but patients with EAC with prior GERD were more likely to have a history of BE. Asymptomatic patients had more advanced disease. Patients with 3 or more BE/EAC-related risk factors formed the largest proportion of patients in both the symptomatic and asymptomatic cohorts. DISCUSSION: Patients with EAC with and without prior GERD symptoms are phenotypically similar, suggesting that BE screening efforts to prevent or detect early EAC should not be restricted to just those with GERD.

NON-ENDOSCOPIC ESOPHAGEAL SAMPLING DEVICE AND BIOMARKER PANEL FOR DETECTION OF BARRETT'S ESOPHAGUS (BE) AND ESOPHAGEAL ADENOCARCINOMA (EAC).

BACKGROUND: We previously reported an encapsulated balloon (EsoCheck TM , EC), which selectively samples the distal esophagus, that coupled with a two methylated DNA biomarker panel (EsoGuard TM , EG), detected Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), with a sensitivity and specificity of 90.3% and 91.7%, respectively. This previous study utilized frozen EC samples. AIM: To assess a next generation EC sampling device and EG assay that utilizes a room temperature sample preservative to enable office-based testing. METHODS: Cases with nondysplastic (ND) and dysplastic (indefinite=IND, low grade dysplasia = LGD, high grade dysplasia = HGD) BE, EAC, junctional adenocarcinoma (JAC) and controls with no intestinal metaplasia (IM) were included. Nurses or physician assistants at six institutions, who were trained in EC administration, delivered the encapsulated balloon per orally and inflated it in the stomach. The inflated balloon was pulled back to sample 5 cm of the distal esophagus, then deflated and retracted into the EC capsule to prevent sample contamination from proximal esophagus. Nextgen EG sequencing assays performed on bisulfite-treated DNA extracted from EC samples determined levels of methylated Vimentin (mVIM) and methylated Cyclin A1 (mCCNA1) in a CLIA-certified laboratory, blinded to patients' phenotypes. RESULTS: A total of 243 evaluable patients - 88 cases (median age 68 years, 78% men, 92% white) and 155 controls (median age 57 years, 41% men, 88% white) - underwent adequate EC sampling. Mean time for EC sampling was just over 3 minutes. The cases included 31 NDBE, 16 IND/LGD, 23 HGD, and 18 EAC/JAC. Thirty-seven (53%) of the non-dysplastic and dysplastic BE cases were short-segment BE (SSBE; < 3 cm). Overall sensitivity for detecting all cases was 85% (95% CI= 0.78-0.93) and specificity was 85% (95% CI=0.79-0.90). Sensitivity for NDBE was 84% (n=37). The EC/EG test detected 100% of cancers. CONCLUSION: The next-generation EC/EG technology has been both successfully updated to incorporate a room temperature sample collection preservative and successfully implemented in a CLIA certified laboratory. When performed by trained personnel, EC/EG detects non-dysplastic BE, dysplastic BE, and cancer with high sensitivity and specificity, replicating the operating characteristics of the initial pilot study of this technology. Future applications utilizing EC/EG to screen broader populations at risk for developing cancer are proposed. SIGNIFICANCE: This multi-center study demonstrates the successful performance of a commercially available clinically implementable non-endoscopic screening test for BE in the U.S., as recommended in the most recent ACG Guideline and AGA Clinical Update. It transitions and validates a prior academic laboratory-based study of frozen research samples over to a CLIA laboratory, one that also integrates a clinically practical room temperature method for sample acquisition and storage, enabling office-based screening.

Effect of Delayed Endoscopy Protocol on Timing and Safety of Endoscopy for Foreign Body Ingestion and Esophageal Food Impaction.

BACKGROUND AND AIMS: Endoscopic procedures for foreign body ingestion (FBI) and esophageal food impactions (EFI) performed during on-call hours are associated with increased stress, risk, and cost. We implemented a Foreign Body Algorithm (FBA) designed to delay all but the most urgent endoscopy for EFI and FBI until regular working hours. METHODS: Using endoscopy records from multiple academic and community hospitals within a large integrated health system in the United states, we identified esophagogastroduodenoscopy (EGD) performed for food impactions and foreign body ingestions occurring between May 2011 and February 2021. RESULTS: We identified 479 EGDs performed for FBI and EFI. The introduction of the FBA was associated with a shorter length of stay (LOS) for overall cases (0.35 vs. 0.8 d P <0.001), day cases (0.16 vs. 1.0 d P <0.001), and night cases (0.40 vs. 0.6 d P =0.03). The introduction of the FBA did not change the rate of overall adverse events (AE) or night AE. AE from the entire cohort was rare (3%; 16 total). Of the AE, most were sedation related. The introduction of the FBA did not affect the overall rate of night cases or AE, but the rate of after-hours endoscopy for intentional ingestions decreased from 17.2% to 3.1% ( P =0.01). CONCLUSION: This is one of the largest studies of esophageal impactions and foreign bodies in adults in the United States, and the first to examine the effects of a protocol designed to avoid after-hours endoscopy. These results suggest that postponing after-hours EGD until the daytime is not associated with adverse safety outcomes or increased LOS.

Outcomes for endoscopic submucosal dissection of pathologically staged T1b esophageal cancer: a multicenter study.

BACKGROUND AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) for T1b esophageal cancer (EC) and its recurrence rates remain unclear in the West. Using a multicenter cohort, we evaluated technical outcomes and recurrence rates of ESD in the treatment of pathologically staged T1b EC. METHODS: We included patients who underwent ESD of T1b EC at 7 academic tertiary referral centers in the United States (n = 6) and Brazil (n = 1). We analyzed demographic, procedural, and histopathologic characteristics and follow-up data. Time-to-event analysis was performed to evaluate recurrence rates. RESULTS: Sixty-six patients with pathologically staged T1b EC after ESD were included in the study. A preprocedure staging EUS was available in 54 patients and was Tis/T1a in 27 patients (50%) and T1b in 27 patients (50%). En-bloc resection rate was 92.4% (61/66) and R0 resection rate was 54.5% (36/66). Forty-nine of 66 patients (74.2%) did not undergo surgery immediately after resection and went on to surveillance. Ten patients had ESD resection within the curative criteria, and no recurrences were seen in a 13-month (range, 3-18.5) follow-up period in these patients. Ten of 39 patients (25.6%) with noncurative resections had residual/recurrent disease. Of the 10 patients with noncurative resection, local recurrence alone was seen in 5 patients (12.8%) and metastatic recurrence in 5 patients (12.8%). On univariate analysis, R1 resection had a higher risk of recurrent disease (hazard ratio, 6.25; 95% confidence interval, 1.29-30.36; P = .023). CONCLUSIONS: EUS staging of T1b EC has poor accuracy, and a staging ESD should be considered in these patients. ESD R0 resection rates were low in T1b EC, and R1 resection was associated with recurrent disease. Patients with noncurative ESD resection of T1b EC who cannot undergo surgery should be surveyed closely, because recurrent disease was seen in 25% of these patients.

Biosimilar strategic implementation at a large health system.

PURPOSE: This article highlights one health system's response to the market influx of biosimilars with the establishment of a process for formulary review and selection of preferred agents and support for therapeutic interchanges. SUMMARY: Through assessment of available literature, insurance payor coverage, and manufacturer-anticipated approvals of biosimilars, a strategic stance was developed to guide biosimilar order preparation, review, adoption, and implementation. The electronic medical record (EMR) is prepared for biosimilar implementation at least 6 to 12 months ahead of anticipated formulary review. The review includes assessment of a class (reference product and available biosimilars) after at least 2 biosimilars become available. Key health-system departments and clinicians are enlisted to support review of clinical, safety, and economic implications. Implementation of a preferred product relies on standard education, formulary availability, and staff awareness to address any perceived patient safety concerns and gather provider support. The standard steps developed now apply to all future biosimilar reviews, adoption plans, and ongoing monitoring. Barriers evaluated include changes in payor coverage and challenges in preparation of the EMR for future biosimilars, meeting precertification team education needs, and providing operational support for pharmacy inventory. CONCLUSION: To date, use of 5 preferred biosimilar products has led to significant cost savings to the institution, and the process has been endorsed by providers. The institution's successes can be attributed to clear communication with stakeholders and the development of a deliberate process, led by a multidisciplinary leadership team, for managing formulary, safety, and operational barriers in a thoughtful and systematic manner.

A survey of physician training and credentialing in endoscopic submucosal dissection in the United States.

BACKGROUND: Endoscopic submucosal dissection (ESD) is technically challenging, has a longer learning curve and a greater complication rate than most new endoscopic procedures. Formal training and credentialing guidelines for ESD are currently lacking in the United States (US). AIM: To survey ESD experts across the US to determine their learning process and obtain their opinion on how training and credentialing for ESD should develop. DESIGN: Anonymous electronic survey. SUBJECTS: ASGE members who are practicing US endoscopists. METHODS: The survey was developed by iterative revisions of questions administered to three investigators who have been performing ESD for > 5 years. The final survey was distributed electronically to US endoscopists who had previously attended ESD expert conferences. RESULTS: Thirty-five (58.3%) of 60 practicing ESD experts responded to the survey. A majority (91%) were in university-based, community, or tertiary care hospitals. All practitioners practiced on porcine explants and observed live ESD procedures as part of the training. Out of the participants, 75.8% received formal supervised hands-on training on porcine explants and/or humans before performing ESD independently. Fifty percent indicated that their facility had written guidelines specifically for ESD credentialing. Four out of 5 felt that credentialing requirements should include attending weekend ESD courses, observing live procedures, practicing on explants, and advanced endoscopic training in interventional endoscopy such as an additional year of fellowship. LIMITATIONS: Survey completion rate of 58.3%. CONCLUSION: ESD training should include practicing on explants, observation of live procedures, training in interventional endoscopy, and attending educational courses. Credentialing guidelines for ESD based on expert opinion need to be developed in the US.

Endoscopic submucosal dissection vs. endoscopic mucosal resection for early Barrett's neoplasia in the West: a retrospective study.

BACKGROUND: The difference in clinical outcomes after endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for early Barrett's esophagus (BE) neoplasia remains unclear. We compared the recurrence/residual tissue rates, resection outcomes, and adverse events after ESD and EMR for early BE neoplasia. METHODS: We included patients who underwent EMR or ESD for BE-associated high grade dysplasia (HGD) or T1a esophageal adenocarcinoma (EAC) at eight academic hospitals. We compared demographic, procedural, and histologic characteristics, and follow-up data. A time-to-event analysis was performed to evaluate recurrence/residual disease and a Kaplan-Meier curve was used to compare the groups. RESULTS: 243 patients (150 EMR; 93 ESD) were included. EMR had lower en bloc (43 % vs. 89 %; P < 0.001) and R0 (56 % vs. 73 %; P = 0.01) rates than ESD. There was no difference in the rates of perforation (0.7 % vs. 0; P > 0.99), early bleeding (0.7 % vs. 1 %; P > 0.99), delayed bleeding (3.3 % vs. 2.1 %; P = 0.71), and stricture (10 % vs. 16 %; P = 0.16) between EMR and ESD. Patients with non-curative resections who underwent further therapy were excluded from the recurrence analysis. Recurrent/residual disease was 31.4 % [44/140] for EMR and 3.5 % [3/85] for ESD during a median (interquartile range) follow-up of 15.5 (6.75-30) and 8 (2-18) months, respectively. Recurrence-/residual disease-free survival was significantly higher in the ESD group. More patients required additional endoscopic resection procedures to treat recurrent/residual disease after EMR (EMR 24.2 % vs. ESD 3.5 %; P < 0.001). CONCLUSIONS: ESD is safe and results in more definitive treatment of early BE neoplasia, with significantly lower recurrence/residual disease rates and less need for repeat endoscopic treatments than with EMR.

A nationwide analysis of pancreatic cancer trial enrollment reveals disparities and participation problems.

BACKGROUND: Our research group recently surveyed the clinical trial landscape in pancreatic adenocarcinoma and identified 430 active trials. These represent an opportunity to expand treatment options for patients with pancreatic adenocarcinoma. Our primary objective was to detail clinical trial participation among patients with pancreatic adenocarcinoma. Our secondary objective was to evaluate survival. METHODS: We queried the National Cancer Database (2004-2016) for patients with pancreatic adenocarcinoma. Patients were stratified by trial participation: clinical trial or non-trial. Multivariable logistic regression was used to identify variables associated with trial participation. The Kaplan-Meier method and multivariable Cox hazards regression were used to analyze survival. RESULTS: In total, 261,483 patients were included: 1,110 (0.4%) were enrolled in a clinical trial. A total of 57 Black patients participated in a clinical trial (0.19% of Black patients). This was lower compared to White patients (n = 955, 0.49% of White patients, P < .001). After adjusting for demographic and clinical factors, Black patients were less likely to be enrolled in a clinical trial (odds ratio = 0.387, P < .001). Patients treated at nonacademic medical centers were less likely to be in a clinical trial. Trial participation was associated with an increased median survival relative to non-trial patients (stage IV: 9.0 vs 3.8 months, P < .001), and this association remained on multivariable regression (hazard ratio = 0.779, P < .001). CONCLUSION: Fewer than 1% of patients with pancreatic adenocarcinoma participated in a clinical trial. There are racial and sociodemographic disparities in clinical trial enrollment. An association was observed between clinical trial participants and prolonged survival.

Massively Parallel Sequencing of Esophageal Brushings Enables an Aneuploidy-Based Classification of Patients With Barrett's Esophagus.

BACKGROUND & AIMS: Aneuploidy has been proposed as a tool to assess progression in patients with Barrett's esophagus (BE), but has heretofore required multiple biopsies. We assessed whether a single esophageal brushing that widely sampled the esophagus could be combined with massively parallel sequencing to characterize aneuploidy and identify patients with disease progression to dysplasia or cancer. METHODS: Esophageal brushings were obtained from patients without BE, with non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (EAC). To assess aneuploidy, we used RealSeqS, a technique that uses a single primer pair to interrogate ∼350,000 genome-spanning regions and identify specific chromosome arm alterations. A classifier to distinguish NDBE from EAC was trained on results from 79 patients. An independent validation cohort of 268 subjects was used to test the classifier at distinguishing patients at successive phases of BE progression. RESULTS: Aneuploidy progression was associated with gains of 1q, 12p, and 20q and losses on 9p and 17p. The entire chromosome 8q was often gained in NDBE, whereas focal gain of 8q24 was identified only when there was dysplasia. Among validation subjects, a classifier incorporating these features with a global measure of aneuploidy scored positive in 96% of EAC, 68% of HGD, but only 7% of NDBE. CONCLUSIONS: RealSeqS analysis of esophageal brushings provides a practical and sensitive method to determine aneuploidy in BE patients. It identifies specific chromosome changes that occur early in NDBE and others that occur late and mark progression to dysplasia. The clinical implications of this approach can now be tested in prospective trials.

High grade dysplasia or esophageal adenocarcinoma in patients with a history of Roux-en-Y gastric bypass surgery: a case series.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is the favored bariatric option in patients with gastroesophageal reflux and Barrett's esophagus because it prevents reflux. Weight loss and decreased reflux following RYGB could theoretically minimize the risk of progression to cancer. We aimed to demonstrate the management of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) developing in patients after RYGB. METHODS: A prospectively maintained database was searched to identify cases of HGD and cancer in RYGB patients. Charts were reviewed for past history, endoscopic findings, endoscopic therapy, and pathology findings. RESULTS: There were five cases where HGD/EAC developed several years after RYGB. The prior bariatric surgery precluded curative esophagectomy, illustrating the management challenges. All but one of the patients were uniquely and successfully managed with endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). CONCLUSIONS: RYGB patients are still at risk of developing esophageal cancer. Patients at risk should be screened prior to RYGB and those with Barret's esophagus need to undergo rigorous endoscopic surveillance following surgery. If detected early, EMR and ESD are invaluable in managing those who progress.

Multifocal Cryoballoon Ablation for Eradication of Barrett's Esophagus-Related Neoplasia: A Prospective Multicenter Clinical Trial.

INTRODUCTION: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE. METHODS: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1-6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year. RESULTS: One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR. DISCUSSION: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).

Clinical, imaging, endoscopic findings, and management of patients with CMV colitis: a single-institute experience.

PURPOSE: To evaluate clinical, laboratory, imaging, endoscopic findings, treatment, and outcomes of patients with CMV colitis. METHODS: The electronic medical records of 652 patients who had an impression of colitis of unspecified etiology via endoscopic findings between 2011 and 2019 were retrospectively reviewed. There were 9 patients with biopsy-proven CMV colitis and associated CT imaging performed within 1 month of diagnosis. Demographic data, past medical history, symptoms, laboratory, imaging, endoscopic and biopsy findings, colitis-related adverse events, treatment, and management were recorded. RESULTS: Within the group of 9 patients (2 men; median age, 60 years), all were in an immunosuppressed state (8/9 on immunosuppressive medication regimen and 1/9 with untreated AIDS). Presenting symptoms of CMV colitis included bloody stools (9/9), abdominal pain (7/9), and diarrhea (7/9). The most common imaging findings were pericolonic stranding (9/9) and bowel wall thickening (9/9). Endoscopic evaluation noted inflammation (9/9), ulceration (9/9), and erythema (8/9) as the most prevalent impressions. As determined by both imaging and endoscopy, the sigmoid colon was most commonly affected. Patients were treated with valganciclovir alone (3/9) or ganciclovir followed by valganciclovir (6/9). Outcomes included perforated colon (1/9), persistent colitis (3/9), discharge to hospice (1/9), and resolution (4/9). CONCLUSIONS: CMV colitis is generally associated with an immunosuppressed state. Imaging and endoscopic findings can mimic inflammatory, ischemic, and infectious colitides. However, CMV colitis should be included in the differential diagnosis in immunocompromised adults who present to emergency department with bloody stools, acute abdominal pain or diarrhea, and have bowel wall thickening and pericolonic stranding on imaging.

Maximizing the Effectiveness of Colonoscopy in the Prevention of Colorectal Cancer.

Colonoscopy is a proven screening test for colorectal cancer; maximizing its effectiveness is the best way to decrease interval colorectal cancer. The adenoma detection rate can be improved by monitoring physician detection rates. Assistive devices and innovative endoscopic equipment may also decrease adenoma miss rates. Complete polypectomy of adenomatous lesions and recommending the proper date for the next examination are important considerations. Advanced polypectomy techniques including endoscopic mucosal resection and endoscopic mucosal dissection have a clear role in the nonsurgical management of large laterally spreading adenomatous polyps that previously would have required surgical resection.

Cryotherapy and Radiofrequency Ablation for Eradication of Barrett's Esophagus with Dysplasia or Intramucosal Cancer.

BACKGROUND AND AIMS: Endoscopic ablation therapy has become the mainstay of treatment of Barrett's associated dysplasia and intramucosal cancer (IMC). The widely available techniques for ablation are radiofrequency ablation (RFA) and cryotherapy. Our aim was to compare eradication rates of metaplasia and dysplasia with both these modalities. PATIENTS AND METHODS: Retrospective review of prospectively collected database of patients who underwent endoscopic therapy for Barrett's dysplasia or IMC from 2006 to 2011 was performed. Demographic features, comorbidities, and endoscopic data including length of Barrett's segment, hiatal hernia size, interventions during the endoscopy and histological results were reviewed. RESULTS: Among 154 patients included, 73 patients were in the RFA and 81 patients were in the cryotherapy group. There was complete eradication of intestinal metaplasia (CE-IM) in 81 (52.6%), complete eradication of dysplasia (CE-D) in 133 (86.4%), and persistent dysplasia or cancer in 19 patients (12.3%). Compared to RFA, cryotherapy patients were found to be older and less likely to have undergone endoscopic mucosal resection. On multivariate analysis, patients who underwent RFA had a threefold higher odds of having CE-IM than those who underwent cryotherapy (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.4-6.0, p = 0.004), but CE-D were similar between the two groups (OR 1.7, 95% CI 0.66-4.3, p = 0.28). CONCLUSIONS: Endoscopic therapy is highly effective in eradication of Barrett's associated neoplasia. Patients who underwent cryotherapy were equally likely to achieve CE-D but not CE-IM than patients who underwent RFA. Patient characteristics and preferences may effect choice of treatment selection and outcomes.

Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett's esophagus.

We report a biomarker-based non-endoscopic method for detecting Barrett's esophagus (BE) based on detecting methylated DNAs retrieved via a swallowable balloon-based esophageal sampling device. BE is the precursor of, and a major recognized risk factor for, developing esophageal adenocarcinoma. Endoscopy, the current standard for BE detection, is not cost-effective for population screening. We performed genome-wide screening to ascertain regions targeted for recurrent aberrant cytosine methylation in BE, identifying high-frequency methylation within the CCNA1 locus. We tested CCNA1 DNA methylation as a BE biomarker in cytology brushings of the distal esophagus from 173 individuals with or without BE. CCNA1 DNA methylation demonstrated an area under the curve of 0.95 for discriminating BE-related metaplasia and neoplasia cases versus normal individuals, performing identically to methylation of VIM DNA, an established BE biomarker. When combined, the resulting two biomarker panel was 95% sensitive and 91% specific. These results were replicated in an independent validation cohort of 149 individuals who were assayed using the same cutoff values for test positivity established in the training population. To progress toward non-endoscopic esophageal screening, we engineered a well-tolerated, swallowable, encapsulated balloon device able to selectively sample the distal esophagus within 5 min. In balloon samples from 86 individuals, tests of CCNA1 plus VIM DNA methylation detected BE metaplasia with 90.3% sensitivity and 91.7% specificity. Combining the balloon sampling device with molecular assays of CCNA1 plus VIM DNA methylation enables an efficient, well-tolerated, sensitive, and specific method of screening at-risk populations for BE.