Clonal evolution of a tumor ecosystem depends on different selection pressures that are principally immune and treatment mediated. We integrate RNA-seq, DNA sequencing, TCR-seq and SNP array data across multiple regions of liver cancer specimens to map spatio-temporal interactions between cancer and immune cells. We investigate how these interactions reflect intra-tumor heterogeneity (ITH) by correlating regional neo-epitope and viral antigen burden with the regional adaptive immune response. Regional expression of passenger mutations dominantly recruits adaptive responses as opposed to hepatitis B virus and cancer-testis antigens. We detect different clonal expansion of the adaptive immune system in distant regions of the same tumor. An ITH-based gene signature improves single-biopsy patient survival predictions and an expression survey of 38,553 single cells across 7 regions of 2 patients further reveals heterogeneity in liver cancer. These data quantify transcriptomic ITH and how the different components of the HCC ecosystem interact during cancer evolution.

Objective To test postoperative serum albumin drop (ΔAlb) as a marker of surgical stress response and early predictor of clinical outcomes. Design Prospective cohort study (NCT02356484). Albumin was prospectively measured in 138 patients undergoing major abdominal surgery. Blood samples were collected before surgery and on postoperative days 0, 1 2 and 3. ΔAlb was compared to the modified estimation of physiologic ability and surgical stress (mE-PASS) score and correlated to the performances of C reactive protein (CRP), procalcitonin (PCT) and lactate (LCT). Postoperative outcomes were postoperative complications according to Clavien classification and Comprehensive Complication Index (CCI), and length of hospital stay (LoS). Setting Department of abdominal surgery in a European tertiary centre. Participants Adult patients undergoing elective major abdominal surgery, with anticipated duration ≥2 hours. Patients on immunosuppressive or antibiotic treatments before surgery were excluded. Results The level of serum albumin rapidly dropped after surgery. ΔAlb correlated to the mE-PASS score (r=0.275, p=0.01) and to CRP increase (r=0.536, p<0.001). ΔAlb also correlated to overall complications (r=0.485, p<0.001), CCI (r=0.383, p<0.001) and LoS (r=0.468, p<0.001). A ΔAlb ≥10 g/L yielded a sensitivity of 77.1% and a specificity of 67.2% (AUC: 78.3%) to predict complications. Patients with ΔAlb ≥10 g/L on POD 1 showed a threefold increased risk of overall postoperative complications. Conclusions Early postoperative decrease of serum albumin correlated with the extent of surgery, its metabolic response and with adverse outcomes such as complications and length of stay. A decreased concentration of serum albumin ≥10 g/L on POD 1 was associated with a threefold increased risk of overall postoperative complications and may thus be used to identify patients at risk.

Background Enhanced recovery after surgery (ERAS) programmes have been shown to decrease complications and hospital stay. The cost‐effectiveness of such programmes has been demonstrated for colorectal surgery. This study aimed to assess the economic outcomes of a standard ERAS programme for pancreaticoduodenectomy. Methods ERAS for pancreaticoduodenectomy was implemented in October 2012. All consecutive patients who underwent pancreaticoduodenectomy until October 2014 were recorded. This group was compared in terms of costs with a cohort of consecutive patients who underwent pancreaticoduodenectomy between January 2010 and October 2012, before ERAS implementation. Preoperative, intraoperative and postoperative real costs were collected for each patient via the hospital administration. A bootstrap independent t test was used for comparison. ERAS‐specific costs were integrated into the model. Results The groups were well matched in terms of demographic and surgical details. The overall complication rate was 68 per cent (50 of 74 patients) and 82 per cent (71 of 87 patients) in the ERAS and pre‐ERAS groups respectively (P = 0·046). Median hospital stay was lower in the ERAS group (15 versus 19 days; P = 0·029). ERAS‐specific costs were €922 per patient. Mean total costs were €56 083 per patient in the ERAS group and €63 821 per patient in the pre‐ERAS group (P = 0·273). The mean intensive care unit (ICU) and intermediate care costs were €9139 and €13 793 per patient for the ERAS and pre‐ERAS groups respectively (P = 0·151). Conclusion ERAS implementation for pancreaticoduodenectomy did not increase the costs in this cohort. Savings were noted in anaesthesia/operating room, medication and laboratory costs. Fewer patients in the ERAS group required an ICU stay.