Background: Postoperative complications after resection of oesophagogastric carcinoma can result in considerable early morbidity and mortality. However, the long-term effects on survival are less clear. Methods: All patients undergoing intentionally curative resection for oesophageal or gastric cancer between 2006 and 2016 were selected from an institutional database. Patients were categorized by complication severity according to the Clavien-Dindo classification (grades 0-V). Complications were defined according to an international consensus statement. The effect of leak and severe non-leak-related complications on overall survival, recurrence and disease-free survival was assessed using Kaplan-Meier analyses to evaluate differences between groups. All factors significantly associated with survival in univariable analysis were entered into a Cox multivariable regression model with stepwise elimination. Results: Some 1100 patients were included, with a median age of 69 (range 28-92) years; 48⋅1 per cent had stage III disease and cancer recurred in 428 patients (38⋅9 per cent). Complications of grade III or higher occurred in 244 patients (22⋅2 per cent). The most common complications were pulmonary (29⋅9 per cent), with a 13⋅0 per cent incidence of pneumonia. Rates of atrial dysrhythmia and anastomotic leak were 10⋅0 and 9⋅6 per cent respectively. Patients with a grade III-IV leak did not have significantly reduced overall survival compared with those who had grade 0-I complications. However, patients with grade III-IV non-leak-related complications had reduced median overall survival (19⋅7 versus 42⋅7 months; P < 0⋅001) and disease-free survival (18⋅4 versus 36⋅4 months; P < 0⋅001). Cox regression analysis identified age, tumour stage, resection margin and grade III-IV non-leak-related complications as independent predictors of poor overall and disease-free survival. Conclusion: Beyond the acute postoperative period, anastomotic leak does not adversely affect survival, however, other severe postoperative complications do reduce long-term overall and disease-free survival. Statistical analysisContinuous variables are described as median (i.q.r. or range) or mean(s.d.), and were compared using the Mann-Whitney U test and Student's t test respectively. The χ 2 test was used for analysis of discrete data. OS was

BackgroundA model to predict chemotherapy response would provide a marked clinical benefit, enabling tailored treatment of oesophageal cancer, where less than half of patients respond to the routinely administered chemotherapy.MethodsCancer cells were established from tumour biopsies taken from individual patients about to undergo neoadjuvant chemotherapy. A 3D-tumour growth assay (3D-TGA) was developed, in which cancer cells were grown with or without supporting mesenchymal cells, then subjected to chemo-sensitivity testing using the standard chemotherapy administered in clinic, and a novel emerging HDAC inhibitor, Panobinostat.RESULTSIndividual patients cancer cells could be expanded and screened within a clinically applicable timescale of 3 weeks. Incorporating mesenchymal support within the 3D-TGA significantly enhanced both the growth and drug resistance profiles of the patients cancer cells. The ex vivo drug response in the presence, but not absence, of mesenchymal cells accurately reflected clinical chemo-sensitivity, as measured by tumour regression grade. Combination with Panobinostat enhanced response and proved efficacious in otherwise chemo-resistant tumours.ConclusionsThis novel method of establishing individual patient oesophageal cancers in the laboratory, from small endoscopic biopsies, enables clinically-relevant chemo-sensitivity testing, and reduces use of animals by providing more refined in vitro models for pre-screening of drugs. The 3D-TGA accurately predicted chemo-sensitivity in patients, and could be developed to guide tailored patient treatment. The incorporation of mesenchymal cells as the stromal cell component of the tumour micro-environment had a significant effect upon enhancing chemotherapy drug resistance in oesophageal cancer, and could prove a useful target for future drug development.

These results suggest the benefit of the adjuvant portion of chemotherapy is limited to those who demonstrate a histopathological response to neoadjuvant chemotherapy. The administration of the adjuvant portion of chemotherapy to patients without a response to neoadjuvant chemotherapy may not provide any survival benefit, while potentially causing increased morbidity.

Aim Postoperative complications following the resection of oesophago-gastric carcinoma can result in considerable early morbidity and mortality, however the long-term effects are less clear. Literature reports are mixed, so it remains unclear if complications reduce survival, as has been demonstrated in colorectal cancer. Background & Methods Some 1100 patients who underwent oesophago-gastric resection between 2006-16 were stratified by complication severity to determine the effect of leak and severe non-leak related complications on overall survival, recurrence and disease free survival. Results The median age was 69 years, 48% had stage III disease, with cancer recurrence in 39%. Clavien-Dindo (CD) complications ≥ III occurred in 22.2% of patients. The most common complications were pulmonary (30%), with a 13% incidence of pneumonia, 10% atrial dysrhythmia and 9.6% anastomotic leak. In comparison to CD 0-I complication free patients, those with CD III-IV leak did not suffer a significantly reduced survival. However patients with CD III-IV non-leak related complications were associated with a significant reduction in median overall survival (19.7 vs. 42.7 months) and disease free survival (18.4 vs. 36.4 months). Cox regression revealed age, stage, resection margin, and CD III-IV non-leak complications as independently associated with poor overall and disease free survival. Conclusion This cohort demonstrates that whilst leak does not affect long-term survival, other severe postoperative complications do significantly reduce overall survival and disease recurrence. A reduction in these complications, such as pneumonia, seen with adoption of hybrid / minimally invasive surgery may help change this pattern of disease recurrence and reduced survival.