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Background: Active surveillance has been proposed for patients with oesophageal cancer in whom there is a complete clinical response after neoadjuvant chemoradiotherapy (nCRT). However, endoscopic biopsies have limited negative predictive value in detecting residual disease. This study determined the location of residual tumour following surgery to improve surveillance and endoscopic strategies., Methods: The present study was based on patients who participated in the prospective preSANO trial with adenocarcinoma or squamous cell carcinoma of the oesophagus or oesophagogastric junction treated in four Dutch hospitals between 2013 and 2016. Resection specimens and endoscopic biopsies taken during clinical response evaluations after nCRT were reviewed by two expert gastrointestinal pathologists. The exact location of residual disease in the oesophageal wall was determined in resection specimens. Endoscopic biopsies were assessed for the presence of structures representing the submucosal layer of the oesophageal wall., Results: In total, 119 eligible patients underwent clinical response evaluations after nCRT followed by standard surgery. Residual tumour was present in endoscopic biopsies from 70 patients, confirmed on histological analysis of the resected organ. Residual tumour was present in the resection specimen from 27 of the other 49 patients, despite endoscopic biopsies being negative. Of these 27 patients, residual tumour was located in the mucosa in 18, and in the submucosa beneath tumour-free mucosa in eight. One patient had tumour in muscle beneath tumour-free mucosa and submucosa., Conclusion: Most residual disease after nCRT missed by endoscopic biopsies was located in the mucosa. Active surveillance could be improved by more sampling and considering submucosal biopsies., (© 2020 The Authors. British Journal of Surgery published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

The vast majority of esophageal adenocarcinoma cases are sporadic and caused by somatic mutations. However, over the last decades several families have been identified with clustering of Barrett's esophagus and esophageal adenocarcinoma. This observation suggests that one or more hereditary factors may play a role in the initiation of Barrett's esophagus and esophageal adenocarcinoma in these families. A Dutch family with clustering of Barrett's esophagus and esophageal adenocarcinoma was identified. Normal DNA obtained from the proband diagnosed with Barrett's esophagus was analyzed with SNP array and exome sequencing. A custom-made panel consisting of potential germline variants was verified in the normal DNA of the affected family members. In addition, the respective tumors were analyzed for somatic loss of the wild type allele or the presence of an inactivating somatic mutation in the wild type allele. Exome sequencing revealed 244 candidate variants in the normal DNA of the proband, of which 212 variants were verified successfully. After the normal DNA of the affected family members was analyzed for the presence of the 212 potential germline variants and subsequently the respective tumors, only one potential germline variant in MSX1 (chr4: 4861985 T > G, c.359T > G, p.V120G, NM_002448) showed loss of the wild type allele in the tumor DNAs of the affected family members. A germline variant in MSX1 was identified in a Dutch family with clustering of Barrett's esophagus and esophageal adenocarcinoma. This finding indicates that the germline defect in MSX1 may be associated with Barrett's esophagus and cancer in this particular family.

Objective: Endoscopic surveillance for Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of evidence that it prevents advanced oesophageal adenocarcinoma (OAC). The aim of this study was to evaluate the impact of endoscopic BO surveillance on tumour stage and survival of patients with neoplastic progression., Design: 783 patients with BO of at least 2 cm were included in a multicentre prospective cohort and followed during surveillance according to the American College of Gastroenterology guidelines. Cases of high-grade dysplasia and OAC were identified during follow-up. OAC staging was performed according to the 7th UICC-AJCC classification. Survival data were collected and crosschecked using death and municipal registries. Data from patients with OAC in the general population were obtained from the Dutch cancer registry. We compared survival of patients with BO with neoplastic progression during surveillance with those of patients without neoplastic progression and patients with OAC in the general population., Results: 53 patients with BO developed high-grade dysplasia or OAC during surveillance. Thirty-five (66%) were classified as stage 0, 14 (26%) as stage 1 and 4 (8%) as stage 2. OAC was diagnosed at an earlier stage during BO surveillance than in the general population (p<0.001). Survival of patients with BO with neoplastic progression was not significantly worse than those of patients without neoplastic progression and similar to survival of patients with stage 0 or stage 1 OAC in the general population., Conclusions: OAC is detected at an earlier stage during BO surveillance than in the general population with good survival rates., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Surveillance is recommended for Barrett's oesophagus (BO) to detect early oesophageal adenocarcinoma (OAC). The aim of this study was to evaluate the cost-effectiveness of surveillance., Design: We included 714 patients with long-segment BO in a multicentre prospective cohort study and used a multistate Markov model to calculate progression rates from no dysplasia (ND) to low-grade dysplasia (LGD), high-grade dysplasia (HGD) and OAC. Progression rates were incorporated in a decision-analytic model, including costs and quality of life data. We evaluated different surveillance intervals for ND and LGD, endoscopic mucosal resection (EMR), radiofrequency ablation (RFA) and oesophagectomy for HGD or early OAC and oesophagectomy for advanced OAC. The incremental cost-effectiveness ratio (ICER) was calculated in costs per quality-adjusted life-year (QALY)., Results: The annual progression rate was 2% for ND to LGD, 4% for LGD to HGD or early OAC and 25% for HGD or early OAC to advanced OAC. Surveillance every 5 or 4 years with RFA for HGD or early OAC and oesophagectomy for advanced OAC had ICERs of €5.283 and €62.619 per QALY for ND. Surveillance every five to one year had ICERs of €4.922, €30.067, €32.531, €41.499 and €75.601 per QALY for LGD. EMR prior to RFA was slightly more expensive, but important for tumour staging., Conclusions: Based on a Dutch healthcare perspective and assuming a willingness-to-pay threshold of €35.000 per QALY, surveillance with EMR and RFA for HGD or early OAC, and oesophagectomy for advanced OAC is cost-effective every 5 years for ND and every 3 years for LGD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)