Dumot, John A.

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.

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.

Abstract 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.

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).

INTRODUCTION: While esophagectomy is the standard treatment for submucosal (T1b) esophageal adenocarcinoma (EAC) and squamous cell cancer (SCC), many elderly patients -the age group that esophageal cancer tends to affect- are not candidates for surgery. Endoscopic submucosal dissection (ESD) is a minimally invasive procedure that allows for en-bloc resection of early esophageal cancer and allows for precise histopathologic staging of the tumor. ESD could be curative in submucosal cancer without lymph node metastasis, and it allows for precise histopathologic staging. To evaluate the long-term outcomes of ESD in patients with EUS-staged T1b esophageal cancer. METHODS: A retrospective multicenter study was performed at three academic hospitals in the U.S. Patients who underwent ESD with a pre-procedural or post-procedural histopathologic diagnosis of T1b N0 M0 EAC or SCC were included in the study. Data was collected on demographics, tumor and procedure characteristics, procedure pathology, and follow-up. Local recurrence was confirmed by endoscopic findings and pathological analysis. Metastasis was confirmed by cross-sectional imaging. The main outcome was a composite of rate of metastasis and local recurrence. Follow-up time was defined as months from initial procedure to recurrence or last follow-up visit if recurrence-free. A time-to-event analysis was performed to evaluate recurrence. RESULTS: Fifty-two patients underwent ESD (mean age 69.6 years +/-9; 35 males) (Table 1). Based on available comorbidity data, 42% patients were not fit for surgery, as determined by an age-adjusted Charlson Comorbidity Index > 6. Twenty tumors (62%) were found to be HGD or T1a on post-ESD specimen analysis, while one was staged as T2. Nineteen patients were staged as T1b after ESD. Immediately after ESD, 6 patients were referred for surgery, 3 underwent chemoradiation therapy, and 6 radiation alone (Table 2). Patients were followed for a median of 18 months, and the calculated 24-month recurrence rate was 13% (Figure 1). CONCLUSION: This multicenter trial showed that ESD for T1b esophageal cancer can be acceptable for patients who deemed not surgical candidates. However, close follow up is necessary. ESD can also serve as a staging procedure, as our data confirms inaccurate EUS-staging of T1b cancer, with 62% of tumors being down-staged to T1a, as has been previously reported.

INTRODUCTION: The difference in long-term outcomes of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for Barrett’s related superficial neoplasia remains unclear. We aimed to compare the rates of local and metachronous recurrence of ESD and EMR in patients with clinically staged BE-associated high-grade dysplasia (HGD) and T1a esophageal adenocarcinoma (EAC). METHODS: Multicenter study at six academic hospitals in the U.S. including patients who underwent ESD for BE-HGD or T1a EAC. Primary outcome was a composite of metastasis and local recurrence rate. A time-to-event analysis was performed to evaluate recurrence. A Kaplan-Meier plot was constructed, and a log-rank test was used to compare the groups. A Cox hazard ratio regression analysis was performed to identify predictors of recurrence. RESULTS: A total of 241 patients were included. 154 underwent EMR, while 84 underwent ESD (Table 1). ESD had higher en bloc (96% vs 33%, P < 0.0001), R0 (76% vs 54%, P = 0.0009) and curative resection rates (75% vs 32%, P < .0001) when compared to EMR. The 24-month local recurrence rate for EMR and ESD was 43% and 11%, respectively ( P = 0.0007) (Figure 1). Significantly more endoscopic resection procedures were required to treat recurrence after EMR compared to after ESD (Table 1). EMR, piecemeal resection, positive margins, and non-curative resection were identified as predictors of recurrence on univariate analysis. En bloc resection remained significant after multivariate analysis (Table 2). CONCLUSION: This multicenter study showed that ESD results in more definitive treatment of BE-associated early neoplasia than EMR, with significant lower recurrence rates and less need for repeat endoscopic therapeutic procedures than EMR.

Combining DNA methylation markers with a swallowable device for sampling the distal esophagus effectively detects Barrett’s neoplasias.

83 Background: Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity and mortality. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study was to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal cancer. Methods: This study includes patients enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from twelve academic and community practices. Endoscopic spray cryotherapy was performed until local tumor eradication was confirmed by biopsy or until treatment was halted due to progression of disease, patient withdrawal or co-morbidities. Results: One-hundred and eight patients (median age 75.5, 79.6% male, 93.5% adenocarcinoma, mean length 5.2 cm) underwent 442 treatments (mean 4.2 per patient). Tumor stages included 40 with T1a, 27 with T1b, 10 with unspecified T1, 15 with T2, and 16 with no T stage reported. One-hundred and six patients completed treatment with complete response of intraluminal disease in 54.7%, including complete response in 74.4% for T1a, 50% for T1b, 65.3% for all T1, 6.7% for T2, and 50% for those with no T stage reported. Mean follow-up was 17.3 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 11 of 108 patients (10.2%) but were present before spray cryotherapy in 3 of 11. Conclusions: This study suggests that endoscopic spray cryotherapy is safe, well tolerated and effective for early esophageal cancer in patients who are not candidates for conventional therapy.