Use of a non-endoscopic immunocytological device (Cytosponge™) for post chemoradiotherapy surveillance in patients with oesophageal cancer in the UK (CYTOFLOC): A multicentre feasibility study.

Background: Effective surveillance strategies are required for patients diagnosed with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC) for whom chemoradiotherapy (CRT) is used as a potentially-curative, organ-sparing, alternative to surgery. In this study, we evaluated the safety, acceptability and tolerability of a non-endoscopic immunocytological device (the Cytosponge™) to assess treatment response following CRT. Methods: This multicentre, single-arm feasibility trial took place in 10 tertiary cancer centres in the UK. Patients aged at least 16 years diagnosed with OSCC or OAC, and who were within 4-16 weeks of completing definitive or neo-adjuvant CRT, were included. Participants were required to have a Mellow-Pinkas dysphagia score of 0-2 and be able to swallow tablets. All patients underwent a single Cytosponge™ assessment in addition to standard of care (which included post-treatment endoscopic evaluation with biopsy for patients undergoing definitive CRT; surgery for those who received neo-adjuvant CRT). The primary outcome was the proportion of consented, evaluable patients who successfully underwent Cytosponge™ assessment. Secondary and tertiary outcomes included safety, study consent rate, acceptance rate, the suitability of obtained samples for biomarker analysis, and the comparative efficacy of Cytosponge™ to standard histology (endoscopy and biopsy or post-resection specimen) in assessing for residual disease. The trial is registered with ClinicalTrials.gov, NCT03529669. Findings: Between 18th April 2018 and 16th January 2020, 41 (42.7%; 95% confidence interval (CI) 32.7-53.2) of 96 potentially eligible patients consented to participate. Thirty-nine (95.1%, 95% CI 83.5-99.4) successfully carried out the Cytosponge™ procedure. Of these, 37 (95%) would be prepared to repeat the procedure. There were only two grade 1 adverse events attributed to use of the Cytosponge™. Thirty-five (90%) of the completed Cytosponge™ samples were suitable for biomarker analysis; 29 (83%) of these were concordant with endoscopic biopsies, three (9%) had findings suggestive of residual cancer on Cytosponge™ not found on endoscopic biopsies, and three (9%) had residual cancer on endoscopic biopsies not detected by Cytosponge™. Interpretation: Use of the CytospongeTM is safe, tolerable, and acceptable for the assessment of treatment response following CRT in OAC and OSCC. Further evaluation of Cytosponge™ in this setting is warranted. Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council.

Standard versus simplified radiofrequency ablation protocol for Barrett's esophagus: comparative analysis of the whole treatment pathway.

Background and study aims The standard radiofrequency ablation (RFA) protocol for Barrett's esophagus (BE) encompasses an intermediary cleaning phase between two ablation sessions. A simplified protocol omitting the cleaning phase is less labor-intensive but equally effective in studies based on single ablation procedures. The aim of this study was to compare efficacy and safety of the standard and simplified RFA protocols for the whole treatment pathway for BE, including both circumferential and focal devices. Patients and methods We performed a retrospective analysis of prospectively collected data on patients receiving RFA between January 2007 and August 2017 at two institutions. Outcomes assessed were: 1) complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM) at 18 months; and 2) rate of esophageal strictures. Results One hundred forty-five patients were included of whom 73 patients received the standard and 72 patients received the simplified protocol. CR-D was achieved in 94.5 % and 95.8 % of patients receiving the standard and simplified protocol, respectively ( P  = 0.71). CR-IM was achieved in 84.9 % and 77.8 % of patients treated with the standard and simplified protocol, respectively ( P  = 0.27). Strictures were significantly more common among patients who received the simplified protocol (12.5 %) compared to the standard protocol (1.4 %; P  = 0.008). The median number of esophageal dilations was one. Conclusion The simplified RFA protocol is as effective as the standard protocol in eradicating BE but carries a higher risk of strictures. This needs to be taken into account, particularly in patients with higher pretreatment risk of strictures, such as those with esophageal narrowing from previous endoscopic mucosal resection (EMR).

Endoscopic measurement of gastric pH associates with persistent acid reflux in patients treated with proton-pump inhibitors for gastroesophageal reflux disease.

Background: Proton-pump inhibitors (PPIs) are the mainstay of gastroesophageal reflux disease (GERD) treatment, however, up to 30% of patients have a poor symptomatic response. PH-impedance is the gold standard to assess whether this is due to persistent acid reflux. We aimed to characterize clinical predictors of persistent esophageal acid reflux on PPIs including gastric pH measured during endoscopy. Methods: We prospectively recruited patients with GERD and/or Barrett's esophagus (BE) on PPIs. All patients completed a symptom questionnaire (RDQ) and underwent gastroscopy with gastric pH analysis, immediately followed by ambulatory 24-hour pH-impedance. We used a modified cut-off of 1.3% for pathological esophageal acid exposure time (AET). Multiple linear regression model was used to analyze the correlation between AET and predictive variables. Results: We recruited 122 patients, of which 92 (75.4%) were included in the final analysis [44 male (47.8%), median age 53 years (IQR: 43-66)]. Forty-four patients (47.8%) had persistent acid reflux with a median total AET of 2.2 (IQR1.2-5.0), as compared to 0.1 (IQR 0.0-0.2) in patients without persistent reflux (n=48; P<.001). There was no difference in age, gender, BMI, PPI-regimen, diagnosis of hiatus hernia or BE, and severity of symptoms between patients with normal and abnormal AET. Median gastric pH was significantly lower in patients with abnormal AET (5.8 vs 6.6, P=0.032) and it correlated with the total AET (P=.045; R2=12.0%). With a pH cut-off of 5.05, single point endoscopic gastric pH analysis had an area under the ROC curve (AUC) of 63.0% (95%CI 51.3-74.7) for prediction of pathological esophageal AET. Conclusions: Symptoms and clinical characteristics are not useful to predict persistent acid reflux in patients on PPIs. One-point gastric pH correlates with 24-hour esophageal AET and could guide clinicians to assess response to PPIs, however, its utility needs validation in larger studies.

Comparative outcomes of radiofrequency ablation for Barrett's oesophagus with different baseline histology.

BACKGROUND: Radiofrequency ablation (RFA) is currently recommended for dysplastic Barrett's oesophagus (BO); however, there are limited data on treatment response when stratified by baseline histology. OBJECTIVE: The objective of this article is to evaluate RFA outcomes and durability for BO with different baseline histology. METHODS: Patients treated with RFA between 2007 and 2017 at a single institution were retrospectively included. Outcome measures were: (a) complete remission of dysplasia (CRD) and intestinal metaplasia (CRIM) at 18 months, (b) complication rate and (c) durability of CRD and CRIM. RESULTS: A total of 148 patients underwent RFA, of whom 113 completed the treatment protocol (21 low-grade dysplasia (LGD), 46 high-grade dysplasia (HGD) and 46 intramucosal carcinoma (IMC)). CRD and CRIM were achieved in 94.7% and 78.8% of patients, respectively. When stratified by baseline histology, there was no significant difference in CRD between groups (LGD, 95.2%; HGD, 95.7%; and IMC, 93.5%; p = 0.89). Similarly, there was no significant difference in CRIM between groups (LGD, 71.4%; HGD, 76.1% and IMC, 87.0%; p = 0.39). CRD and CRIM durability at 24 months for LGD, HGD and IMC were 100%, 97.7% and 100% (log rank p = 0.31), and 100%, 89.0% and 95.5%, respectively (log rank p = 0.62). CONCLUSION: Baseline histology is not a predictor of RFA response. Once CRD and CRIM are achieved, these effects are durable over time.