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Aims: Determining prognosis following poor response to neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma (OAC) remains challenging. An immunosuppressive tumour microenvironment (TME) as well as immune infiltrate density and composition are considered to play a critical role in the immune interaction between host and tumour and can predict therapy response and survival in many cancers, including gastrointestinal malignancies. The aim of this study was to establish the TME characteristics associated with survival following a poor response to nCRT. Methods and results: The prognostic significance of OAC-associated CD3+, CD4+, CD8+, forkhead box protein 3 (FoxP3+) and programmed cell death ligand 1 (PD-L1) expression was studied by immunohistochemistry and quantified by automated image analysis in 123 patients who underwent nCRT and curative resection. Results from good and poor responders were contrasted and immune infiltration was related to disease course in both groups. Subsequently a cohort of 57 patients with a moderate response to nCRT was analysed in a similar fashion. Tumour cell percentage positively correlated to immune infiltration markers. In good and moderate responders, none of the immune infiltrate parameters was associated with survival; in poor responders CD8+ was an independent negative predictor of OS in univariate analysis (P = 0.03) and high CD8+ infiltration was associated with worse OS (15 versus 32 months, P = 0.042). Conclusion: A high CD8+ density is an independent biomarker of poor OS in poor responders to nCRT, but not in good and moderate responders. Our results suggest that patients with a poor response to nCRT but concomitant high CD8+ counts in the resection specimen require adjuvant therapy.

Background Patients with hereditary diffuse gastric cancer and a CDH1 mutation have a 60–80 per cent lifetime risk of developing diffuse gastric cancer. Total prophylactic gastrectomy eliminates this risk, but is associated with considerable morbidity. The effectiveness (removal of all gastric mucosa) and outcomes of this procedure were evaluated retrospectively. Methods All consecutive individuals undergoing a prophylactic gastrectomy for a CDH1 mutation or gastric signet ring cell foci at the authors' institute between 2005 and 2017 were included. Results In 25 of 26 patients, intraoperative frozen-section examination (proximal resection margin) was used to verify complete removal of gastric mucosa. All definitive resection margins were free of gastric mucosa, but only after the proximal margin had been reresected in nine patients. In the first year after surgery, five of the 26 patients underwent a relaparotomy for adhesiolysis (2 patients) or jejunostomy-related complications (3 patients). Six patients were readmitted to the hospital within 1 year for nutritional and/or psychosocial support (4 patients) or surgical reintervention (2 patients). Mean weight loss after 1 year was 15 (95 per cent c.i. 12 to 18) per cent. For the 25 patients with a follow-up at 1 year or more, functional complaints were reported more frequently at 1 year than at 3 months after the operation: bile reflux (15 versus 11 patients respectively) and dumping (11 versus 7 patients). The majority of patients who worked or studied before surgery (15 of 19) had returned fully to these activities within 1 year. Conclusion The considerable morbidity and functional consequences of gastrectomy should be considered when counselling individuals with an inherited predisposition to diffuse gastric cancer. Intraoperative frozen-section examination is recommended to remove all risk-bearing gastric mucosa.

Background Patients with a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer may benefit from non-surgical management. The aim of this study was to determine the diagnostic performance of visual response assessment of the primary tumour after nCRT on T2-weighted (T2W) and diffusion-weighted (DW) MRI. Methods Patients with locally advanced oesophageal cancer who underwent T2W- and DW-MRI (1·5 T) before and after nCRT in two hospitals, between July 2013 and September 2017, were included in this prospective study. Three radiologists evaluated T2W images retrospectively using a five-point score for the assessment of residual tumour in a blinded manner and immediately rescored after adding DW-MRI. Histopathology of the resection specimen was used as the reference standard; ypT0 represented a pCR. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC) and interobserver agreement were calculated. Results Twelve of 51 patients (24 per cent) had a pCR. The sensitivity and specificity of T2W-MRI for detection of residual tumour ranged from 90 to 100 and 8 to 25 per cent respectively. Respective values for T2W + DW-MRI were 90–97 and 42–50 per cent. AUCs for the three readers were 0·65, 0·66 and 0·68 on T2W-MRI, and 0·71, 0·70 and 0·70 on T2W + DW-MRI (P = 0·441, P = 0·611 and P = 0·828 for readers 1, 2 and 3 respectively). The κ value for interobserver agreement improved from 0·24–0·55 on T2W-MRI to 0·55–0·71 with DW-MRI. Conclusion Preoperative assessment of residual tumour on MRI after nCRT for oesophageal cancer is feasible with high sensitivity, reflecting a low chance of missing residual tumour. However, the specificity was low; this results in overstaging of complete responders as having residual tumour and, consequently, overtreatment.