Impact of preoperative statin medication on long-term outcomes after pancreatoduodenectomy for ductal adenocarcinoma: an international multicentric cross-sectional study.

PURPOSE Statin treatment has been shown in certain population studies and meta-analyses to improve survival of patients with pancreatic ductal adenocarcinoma (PDAC). This study assessed if patients with statin treatment had better overall survival (OS) and disease-free survival (DFS) after upfront pancreatoduodenectomy for PDAC. METHODS Consecutive PDAC patients were retrospectively collected from three centers in Europe and USA (study period: 2000-2017). Adult patients who underwent upfront pancreatoduodenectomy and survived the first 90 postoperative days were included. Patients with metastasis at diagnosis or with macroscopic incomplete resection were excluded. Patients were considered under statin if started at least one month before pancreatoduodenectomy. Survival rates were calculated using Kaplan-Meier method and compared with log-rank test. RESULTS A total of 496 patients were included. Median age was 67 years (IQR 59-75), 48% (n = 236) were women, and 141 patients (28%) received statin treatment already preoperatively. Patients with and without statin treatment were comparable in terms of demographics and pre-/intraoperative characteristics, except for age and pre-existing diabetes. Median OS and DFS were similar in patients with and without statin treatment (OS: 29, 95% CI 22-36 vs. 27 months, 95% CI 22-32, p = 0.370, DFS: 18, 95% CI 14-22 vs. 16 months, 95% CI 14-18, p = 0.430). On multivariable Cox regression, lymph node involvement (HR 1.9, 95% CI 1.6-2.2, p < 0.001), tumor differentiation (HR 1.3, 95% CI 1.1-1.6, p = 0.003), and postoperative chemotherapy (HR 0.5, 95% CI 0.4-0.7, p < 0.001) were predictors of OS, whereas statin treatment was not a prognostic factor (HR 0.9, 95% CI 0.7-1.2, p = 0.376). CONCLUSION In this international cohort of PDAC patients, statin treatment did not influence survival after upfront pancreatoduodenectomy. Nodal involvement, tumor differentiation, and postoperative chemotherapy were independent predictors of OS

An algorithm based on the postoperative decrease of albumin (ΔAlb) to anticipate complications after liver surgery

International audienceBackground Perioperative decrease of albumin (Delta Alb) appeared as a promising predictor of complications after digestive surgery, but its role after liver surgery remains unclear. This study aimed to analyze whether and how Delta Alb can be used to predict complications after liver surgery. Methods A bicentric retrospective analysis of patients undergoing liver surgery (2010-2016) was performed, following TRIPOD guidelines. The preoperative and postoperative difference of albumin was calculated on POD 0 and defined as Delta Alb. Patients with any missing variable were excluded. The primary endpoint was overall complications according to the Clavien classification. A multiparametric algorithm based on Delta Alb was generated to optimize prediction performance. Results A total of 110 patients were analyzed. At least one complication occurred in 66 (60%) patients. Patients with and without complication showed a Delta Alb of 15.8 vs. 9.5 g/L (p&lt;0.001). Area under ROC curve (AUC) of Delta Alb was 0.75 (p&lt;0.01.). The Delta Alb-based algorithm showed an AUC of 0.84 (p&lt;0.01), significantly improving performance (p=0.03). Multivariable analysis identified Delta Alb as independent predictor of complications (HR, 1.12; 95% CI, 1.01-1.07; p = 0.002). Conclusions Delta Alb appeared as a promising predictor independently associated with the risk of complication after liver surgery. The study presents a novel decision-tree based on Delta Alb to anticipate complications

External validation of three lymph node ratio-based nomograms predicting survival using an international cohort of patients with resected pancreatic head ductal adenocarcinoma.

INTRODUCTION Lymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms using an international cohort. MATERIALS AND METHODS Consecutive PDAC patients who underwent upfront pancreatoduodenectomy from six centers (Europe/USA) were collected (2000-2017). Patients with metastases, R2 resection, missing LNR data, and who died within 90 postoperative days were excluded. The updated Amsterdam nomogram, the nomogram by Pu et al., and the nomogram by Li et al. were selected. For the validation, calibration, discrimination capacity, and clinical utility were assessed. RESULTS After exclusion of 176 patients, 1'113 patients were included. Median overall survival (OS) of the cohort was 23 months (95% CI: 21-25). For the three nomograms, Kaplan-Meier curves showed significant OS diminution with increasing scores (p < 0.01). All nomograms showed good calibration (non-significant Hosmer-Lemeshow tests). For the Amsterdam nomogram, area under the ROC curve (AUROC) for 3-year OS was 0.64 and 0.67 for 5-year OS. Sensitivity and specificity for 3-year OS prediction were 65% and 59%. Regarding the nomogram by Pu et al., AUROC for 3- and 5-year OS were 0.66 and 0.70. Sensitivity and specificity for 3-year OS prediction were 68% and 53%. For the Li nomogram, AUROC for 3- and 5-year OS were 0.67 and 0.71, while sensitivity and specificity for 3-year OS prediction were 63% and 60%. CONCLUSION The three nomograms were validated using an international cohort. Those nomograms can be used in clinical practice to evaluate survival after pancreatoduodenectomy for PDAC

Intratumoral heterogeneity and clonal evolution in liver cancer

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

Assessment of the Predictive Value of Preoperative Serum Albumin and Postoperative Albumin Drop (&Delta;Alb) for Complications after Pancreas Surgery: A Single-Center Cross-Sectional Study

Background: Serum albumin has been shown to be predictive of complications after various gastrointestinal operations. The present study aimed to assess whether preoperative serum albumin and serum albumin drop on postoperative day 1 are associated with postoperative complications after pancreatic surgery. Methods: A single-center cross-sectional study was performed. All patients who underwent pancreatectomy between January 2010 and June 2019 and had preoperative serum albumin value and serum albumin value on postoperative day 1 were included. &Delta;Alb was defined as the difference between preoperative serum albumin and serum albumin on postoperative day 1. Binary logistic regressions were performed to determine independent predictors of postoperative complications. Results. A total of 185 patients were included. Pancreatoduodenectomies were performed in 133 cases, left pancreatectomies in 36, and other pancreas operations in 16. The preoperative serum albumin value was found to be an independent predictor of complications (OR 0.9, 95%CI 0.9&ndash;1.0, p = 0.041), whereas &Delta;Alb was not significantly associated with postoperative complications (OR 1.0, 95%CI 0.9&ndash;1.1, p = 0.787). The threshold of 44.5 g/L for preoperative albumin level was found to have the highest combined sensitivity and specificity based on the maximum Youden index. Patients with preoperative albumin &lt; 44.5 g/L had a higher incidence of postoperative complications and higher median comprehensive complication index than patients with preoperative albumin &ge;&nbsp;44.5 g/L. Conclusions: This study highlighted that preoperative serum albumin is an independent predictor of postoperative complications after pancreas surgery