Patient and operative factors influence delayed discharge following bariatric surgery in an enhanced recovery setting.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) programs have been widely adopted in bariatric surgery. However, not all patients are successfully managed in the ERAS setting and there is currently little way of predicting the patients who will deviate from the program. Early identification of these patients could allow for more tailored protocols to be implemented preoperatively to address the issues, thereby improving patient outcomes. OBJECTIVES: The aim of this study was to elucidate the factors which preclude discharge by comparing patients who were successfully discharged by the end of the first postoperative day (POD 0/1) to those who stayed longer, including revisional surgery in this analysis. SETTING: A tertiary, high-volume Bariatric Centre, United Kingdom. METHODS: A retrospective analysis was performed of all patients undergoing bariatric surgery in a single centre in 1 year. Multivariate analyses compared patient and operative variables between patients who were discharged on POD 0/1 and those who stayed longer. RESULTS: A total of 288 bariatric operations were performed: 78% of operations performed were laparoscopic Roux-en-Y gastric bypass; 22% laparoscopic sleeve gastrectomy. Of these cases, 13% were revisional operations. Four patients returned to theatre on the index admission. 81% of patients were discharged by POD 0/1. A re-presentation within 30 days was seen in 6% of patients. There was no significant difference in length of stay for the type of operation performed (P = .86). Patients who had a revisional procedure were not more likely to stay longer. Length of stay was also independent of age, BMI, and comorbidities. Caucasian patients were more likely to be discharged on POD 0/1 than those of other ethnicities (90% versus 78%; P = .02). Operations performed by trainee surgeons, under consultant supervision, were significantly more likely to be discharged on POD 0/1 (P = .03). However, a logistic regression analysis was unable to predict patients who had a prolonged stay. CONCLUSIONS: Patient length of stay is independent of BMI, operation, and comorbidities and these factors do not need special consideration in ERAS pathways. Patients undergoing revisional procedures can be managed in the same way as those having primary procedures, with a routine POD 0/1 discharge. However, the impact of individual patient factors, and their interaction, is complex and cannot predict overstay.

Extrachromosomal DNA in the cancerous transformation of Barrett's oesophagus.

Oncogene amplification on extrachromosomal DNA (ecDNA) drives the evolution of tumours and their resistance to treatment, and is associated with poor outcomes for patients with cancer1-6. At present, it is unclear whether ecDNA is a later manifestation of genomic instability, or whether it can be an early event in the transition from dysplasia to cancer. Here, to better understand the development of ecDNA, we analysed whole-genome sequencing (WGS) data from patients with oesophageal adenocarcinoma (EAC) or Barrett's oesophagus. These data included 206 biopsies in Barrett's oesophagus surveillance and EAC cohorts from Cambridge University. We also analysed WGS and histology data from biopsies that were collected across multiple regions at 2 time points from 80 patients in a case-control study at the Fred Hutchinson Cancer Center. In the Cambridge cohorts, the frequency of ecDNA increased between Barrett's-oesophagus-associated early-stage (24%) and late-stage (43%) EAC, suggesting that ecDNA is formed during cancer progression. In the cohort from the Fred Hutchinson Cancer Center, 33% of patients who developed EAC had at least one oesophageal biopsy with ecDNA before or at the diagnosis of EAC. In biopsies that were collected before cancer diagnosis, higher levels of ecDNA were present in samples from patients who later developed EAC than in samples from those who did not. We found that ecDNAs contained diverse collections of oncogenes and immunomodulatory genes. Furthermore, ecDNAs showed increases in copy number and structural complexity at more advanced stages of disease. Our findings show that ecDNA can develop early in the transition from high-grade dysplasia to cancer, and that ecDNAs progressively form and evolve under positive selection.

Identification of Subtypes of Barrett's Esophagus and Esophageal Adenocarcinoma Based on DNA Methylation Profiles and Integration of Transcriptome and Genome Data.

BACKGROUND & AIMS: Esophageal adenocarcinomas (EACs) are heterogeneous and often preceded by Barrett's esophagus (BE). Many genomic changes have been associated with development of BE and EAC, but little is known about epigenetic alterations. We performed epigenetic analyses of BE and EAC tissues and combined these data with transcriptome and genomic data to identify mechanisms that control gene expression and genome integrity. METHODS: In a retrospective cohort study, we collected tissue samples and clinical data from 150 BE and 285 EAC cases from the Oesophageal Cancer Classification and Molecular Stratification consortium in the United Kingdom. We analyzed methylation profiles of all BE and EAC tissues and assigned them to subgroups using non-negative matrix factorization with k-means clustering. Data from whole-genome sequencing and transcriptome studies were then incorporated; we performed integrative methylation and RNA-sequencing analyses to identify genes that were suppressed with increased methylation in promoter regions. Levels of different immune cell types were computed using single-sample gene set enrichment methods. We derived 8 organoids from 8 EAC tissues and tested their sensitivity to different drugs. RESULTS: BE and EAC samples shared genome-wide methylation features, compared with normal tissues (esophageal, gastric, and duodenum; controls) from the same patients and grouped into 4 subtypes. Subtype 1 was characterized by DNA hypermethylation with a high mutation burden and multiple mutations in genes in cell cycle and receptor tyrosine signaling pathways. Subtype 2 was characterized by a gene expression pattern associated with metabolic processes (ATP synthesis and fatty acid oxidation) and lack methylation at specific binding sites for transcription factors; 83% of samples of this subtype were BE and 17% were EAC. The third subtype did not have changes in methylation pattern, compared with control tissue, but had a gene expression pattern that indicated immune cell infiltration; this tumor type was associated with the shortest time of patient survival. The fourth subtype was characterized by DNA hypomethylation associated with structure rearrangements, copy number alterations, with preferential amplification of CCNE1 (cells with this gene amplification have been reported to be sensitive to CDK2 inhibitors). Organoids with reduced levels of MGMT and CHFR expression were sensitive to temozolomide and taxane drugs. CONCLUSIONS: In a comprehensive integrated analysis of methylation, transcriptome, and genome profiles of more than 400 BE and EAC tissues, along with clinical data, we identified 4 subtypes that were associated with patient outcomes and potential responses to therapy.