Shah, Tilak

INTRODUCTION: The study aimed to develop consensus recommendations for the safe and appropriate use of liquid nitrogen spray cryotherapy in Barrett's esophagus and esophageal cancer. METHODS: Statements were initially formulated and grouped into categories of indications, training, preprocedure, intraprocedure, and postprocedure recommendations, frequency/timing of repeat procedures, and contraindications. Two investigators assessed the strength of the evidence for each statement using Grading of Recommendations Assessment, Development, and Evaluation methodology. Nineteen experts were invited to participate in a modified Delphi process. For statements that received >80% agreement, minor iterative edits were performed until there was unanimous consensus. If a threshold of 80% agreement was not reached, the statement was modified based on feedback and included in the next Delphi round. Statements were rejected if no consensus was reached after 3 rounds. RESULTS: After 3 Delphi rounds, 41 of 42 statements were accepted either in their original version (n = 11) or after modification based on expert input (n = 30). DISCUSSION: Through a modified Delphi process, we developed expert and evidence-based consensus recommendations to guide safe and appropriate use of liquid nitrogen spray cryotherapy in Barrett's esophagus and esophageal cancer.

Background Dysphagia palliation in inoperable esophageal cancer continues to be a challenge. Self-expandable metal stents have been the mainstay of endoscopic palliation but have a significant risk of adverse events (AEs). Liquid nitrogen spray cryotherapy is an established modality that can be used with systemic therapy. This study reports the outcomes of cryotherapy, including dysphagia and quality of life (QoL), in patients receiving systemic therapy. Methods This was a prospective multicenter cohort study of adults with inoperable esophageal cancer who underwent cryotherapy. QoL and dysphagia scores before and after cryotherapy were compared. Results 55 patients received 175 cryotherapy procedures. After a mean of 3.2 cryotherapy sessions, mean QoL improved from 34.9 at baseline to 29.0 at last follow-up (P < 0.001) and mean dysphagia improved from 1.9 to 1.3 (P = 0.004). Patients receiving more intensive cryotherapy (≥ 2 treatments within 3 weeks) showed a significantly greater improvement in dysphagia compared with those not receiving intensive therapy (1.2 vs. 0.2 points; P = 0.003). Overall, 13 patients (23.6 %) received another intervention (1 botulinum toxin injection, 2 stent, 3 radiation, 7 dilation) for dysphagia palliation. Within the 30-day post-procedure period, there were three non-cryotherapy-related grade ≥ 3 AEs (all deaths). The median overall survival was 16.4 months. Conclusion In patients with inoperable esophageal cancer receiving concurrent systemic therapy, adding liquid nitrogen spray cryotherapy was safe and associated with improvement in dysphagia and QoL without causing reflux. More intensive treatment showed a greater improvement in dysphagia and should be considered as the preferred approach.

260 Background: dysphagia (dys) palliation in non-operable esophageal cancer (EC) continues to be a challenge. While chemotherapy and radiation help with dys, many patients require endoscopic interventions during their illness. Self-expanding metal stents have been the mainstay of endoscopic interventions but have a significant risk of severe adverse events and prevent the patient from being able to lie flat without severe reflux. Cryotherapy (cryo) is an emerging technique that can be used while the patient is receiving systemic therapy (ST). Previous retrospective studies showed improvement in dys with a favorable adverse event profile but did not report on quality of life (QOL) or reflux symptoms in patients receiving ST. Prospective studies have shown modest improvement in dys and QOL in patients not receiving ST. This prospective study reports the outcomes of cryo including dys, QOL, reflux symptoms and adverse events (AE) in patients receiving ST. Methods: A prospective multicenter cohort study of 35 adult inoperable EC patients undergoing cryo from Sep 2017 to Aug 2021. QoL was assessed using a modified EORTC QLQ-OES18 questionnaire (score 18 to 72, higher scores indicating worse QoL) while dys was measured using a 4-point Likert scale (0, no Dys; 1, Dys to solids; 2, Dys to semi-solids; 3, Dys to liquids; 4, Dys to saliva) at the start of cyro and 1-2 weeks post cryo. Paired t-test was used to evaluate changes in QoL and Dys between pre- and post-cryo. Results: There were 29 males and 6 females (30 stage IV and 5 stage III at diagnosis). Among 35 patients, a total of 104 cryo procedures were performed, with a mean of 3 per patient. The median number of tumor sites treated per cryo was 2 while the median number of cryo cycles delivered per tumor site was 3. The median total freeze time per tumor site was 60 seconds. The mean QoL score improved significantly from 31.8 pre-cryo to 28.2 with one cryo session (improvement of 3.6 points; p < 0.001). The mean dysphagia score improved significantly from 1.42 to 1.05 per cryo session (improvement of 0.37 points; p = 0.002). The mean After a mean of 3 cryo sessions, QoL score improved significantly from 35.9 pre-cryo to 29.8 post-cryo (improvement of 6 points; p = 0.001) and the mean dysphagia score improved significantly from 1.97 pre-cryo to 1.25 post-cryo (improvement of 0.72 points; p = 0.004). 86.5% of patient were able to sleep lying flat without heartburn or regurgitation. 6 patients received another intervention (1 stenting, 3 radiation and 2 dilation) for Dys palliation. 8 patients underwent feeding tube placement. Cryotherapy related grade 3 or higher adverse events occurred after 3 cryo sessions. Conclusions: Cryotherapy for palliation in non operable esophageal cancer improved dysphagia and quality of life without causing reflux and had a favorable adverse event profile with most patients not needing another intervention for dysphagia palliation.

Abstract Background For surveillance of Barrett’s esophagus (BE), the current standard of random 4-quadrant biopsies misses 10 – 50 % of esophageal neoplasms, and does not permit real-time decision-making. Probe-based confocal laser endomicroscopy (pCLE) permits real-time in vivo histologic assessment of esophageal mucosa during upper endoscopy. Prospective studies comparing the accuracy of pCLE to 4-quadrant biopsies in routine clinical practice are lacking. Methods Consecutive patients with BE underwent high definition white light and narrow-band imaging followed by pCLE and targeted biopsy or mucosal resection. Four-quadrant biopsies were obtained during the same session. Baseline variables, real-time pCLE interpretation, and histology results were prospectively recorded. Blinded expert review of pCLE sequences and histology specimens was performed. A sample size of 64 patients was calculated a priori based on 3 % estimated prevalence of high grade dysplasia (HGD) or cancer. Results In total, 66 patients were included in the study. The prevalence of HGD or cancer was 4.55 %. Both real-time and blinded pCLE correctly identified all cases of cancer. For the primary outcome, real-time pCLE was 98 % specific but only 67 % sensitive for HGD/cancer compared to non-blinded pathologist interpretation. For HGD and cancer, inter-observer agreement was substantial between real-time and blinded endomicroscopists (kappa = 0.6). pCLE identified dysplasia in 75 % of cases where both blinded and unblinded pathology interpretation was low grade dysplasia. Conclusions pCLE demonstrates high specificity for detecting dysplasia and cancer, but lower sensitivity may limit its utility in routine BE surveillance. pCLE may have a role in confirming LGD in real-time before eradication therapy.