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Introduction In oesophageal adenocarcinoma with an apparent pathological complete response (pCR) to neoadjuvant therapy (NAT) there remains debate as to whether oesophagectomy is required. Single Cell RNA sequencing (scRNAseq) enables identification and characterisation of cell populations at higher resolution than diagnostic techniques. Method ScRNAseq was used to determine transcriptomic profiles of cell populations in 24 OAC tumours and 13 matched normal samples. Five were also analysed using bulk RNA sequencing and high-precision mass spectrometry proteomics. Immunohistochemistry (IHC) was used to validate pCR. Paired scRNAseq analysis of pre-and post-treatment specimens from three further patients was used to compare transcriptomic profiles before and after NAT. Cancer cells (CCs) were assigned a cancer stem cell (CSC) score curated from published gene sets. Result We analysed a total of 22,738 single cells forming 29 different cell phenotypes. In two samples with apparent pCR, IHC staining, bulk RNA sequencing and proteomics of post-treatment samples failed to identify CCs. ScRNAseq, conversely, revealed persistent CCs (12/978 and 45/774). Transcriptomic analysis identified upregulation of stem cell markers and high CSC scores in these cells. Conclusion We have shown that CCs persist beneath the lower detection limit of standard approaches in apparent pCR. These cells express marker genes and expression programs consistent with CSCs. CSCs are a critical subpopulation that drive tumour initiation, growth, invasion, metastasis and resistance to therapy. These gene expression programs are not enriched in non-responders and straight to surgery samples. Oesophagus sparing treatment algorithms in pCR may subject patients to unnecessary risk of progression. Take-home message Cancer cells remain within tumours after apparent complete pathological response. These cells express stem cell markers associated with resistance to therapy and cancer progression.

Introduction: Boerhaave's syndrome is a life-threatening spontaneous perforation of the esophagus associated with significant morbidity and mortality. Historically, thoracotomy has been the mainstay of treatment, but is associated with high morbidity and pain. Minimally invasive approaches provide alternative treatment possibilities. This systematic review together with inclusion of a case series from a tertiary esophagogastric unit assesses current evidence focused on minimally invasive surgical management of this condition. Methods: A systematic review was conducted in line with MOOSE (Meta-analyses Of Observational Studies in Epidemiology) guidelines. Electronic databases PubMed, MEDLINE, and Cochrane Library were searched, and articles focusing on the minimally invasive management of Boerhaave's syndrome were identified and scrutinized. We also report demographics and outcomes for a consecutive case series of patients with acute Boerhaave's syndrome managed via thoracoscopy. Results: Fifteen studies were included comprising 5 retrospective cohort studies and 10 case reports. Management strategies were divided into three categories: thoracoscopic, endoscopic, and laparoscopic. Overall mortality rates for each treatment modality were 2%, 13%, and 33%, and treatment success rates 98%, 38%, and 67%, respectively. Postoperative infective complications were seen in 79% of patients, with only 2 patients requiring salvage thoracotomy. In our local case series, we report 4 consecutive patients managed with thoracoscopy, with a 100% treatment success rate. Conclusion: Minimally invasive approaches in the management of Boerhaave's syndrome are safe and effective. We propose a selective management algorithm involving a minimally invasive approach to management of this life-threatening condition. Registered with local clinical outcomes team as service evaluation. (Approval number sev/0171).

Background Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20–30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. Methods Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. Results A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal–external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). Conclusion The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients., Early recurrence after surgery for adenocarcinoma of the oesophagus is common. A risk prediction model was derived using modern machine learning methods that accurately predicts risk of early recurrence using postoperative pathology. Machine learning may help

The outcome after laparoscopic Nissen fundoplication can be assessed by either clinical symptoms or objective tests. Outcomes from objective tests are often held in higher regard than clinical data when determining the merits, or otherwise, of various antireflux surgery procedures. In this study, we sought to determine whether there is a relationship between postoperative symptoms and parameters measured by esophageal manometry to determine whether early postoperative esophageal manometry is a useful investigation for the routine assessment of post fundoplication outcome.One hundred and forty-three patients who had undergone a laparoscopic Nissen fundoplication, clinical follow-up at 3 months and 5 years after surgery, and esophageal manometry at 3 months after fundoplication as part of routine follow-up in 1 of 5 clinical trials were studied. Nineteen of these patients also underwent manometry 5 years after fundoplication. Postoperative symptoms were prospectively determined by applying a standardized questionnaire, which assessed dysphagia, heartburn, bloat symptoms, and overall satisfaction using analog scales. Patients were classified into different groups according to the analog scores for clinical symptoms. Correlations between clinical and postoperative manometry outcomes were sought.No significant associations were found between parameters measured by esophageal manometry (lower esophageal sphincter resting and residual relaxation pressures, peristaltic amplitude and normal peristaltic propagation) and clinical parameters (dysphagia, heartburn, bloating, and overall satisfaction) for all time points -- 3 months postoperative manometry vs symptoms at 3 months and 5 years, 5 years postoperative manometry vs symptoms at 5 years, except for a weak (r = -0.17, p = 0.042) correlation between the percentage of successfully propagated swallows at 3 months and dysphagia for solids at 5 years.Postoperative esophageal manometry parameters at 3 months and 5 years after surgery were not associated with any clinically important differences in the postoperative symptoms of heartburn, dysphagia, bloat or with overall satisfaction with the surgical outcome. The routine use of esophageal manometry to assess the outcome after Nissen fundoplication does not predict clinical outcome.

Background Laparoscopic Nissen fundoplication is now the most common operative procedure for treatment of gastroesophageal reflux disease, although longterm clinical outcomes after this procedure remain uncertain. Study Design Outcomes for 250 patients who underwent Nissen (total) fundoplication at least 10 years ago (September 1991 to August 1995) were determined prospectively using a structured questionnaire that evaluated clinical symptom scores for heartburn, dysphagia, and satisfaction with clinical outcomes. Results Clinical followup data for at least 10 years (120 to 167 months) after operation were available for 226 patients, an additional 21 patients had died, making outcomes for 247 patients (99%). Of the three (1%) remaining patients, one was lost to followup and dementia developed in two. One hundred eighty-seven (83%) patients were highly satisfied with the clinical outcomes. One hundred eighty-nine (84%) had good or excellent control of heartburn. Symptom scores for heartburn, dysphagia, and overall satisfaction were unchanged from 5-year followup data. Forty-two (17%) patients underwent revision operations, 28 (22%) were in the first 125 patients and 14 (11%) in the subsequent 125 patients. Antireflux medication use increased gradually, resulting in 47 (21%) patients using medication at 10 years. Of 21 deaths, 1 was postoperative and the remaining 20 were similar to that predicted for a matched population. A high preoperative heartburn score correlated with high patient satisfaction and lower dysphagia score at 10 or more years (p = 0.038 and p=0.041, respectively). Conclusions Laparoscopic Nissen fundoplication is an effective longterm treatment for gastroesophageal reflux disease.