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Background: Short-term perioperative administration of probiotics was shown to alleviate postoperative complications and promote liver recovery among patients undergoing resection for liver malignancy. The mechanisms by which probiotic bacteria effectively influence the gut microbiome composition during the perioperative time are controversial. Here, we aim to elucidate the short-term direct biological effect of probiotic microbiota–derived vesicles on host liver cells during the perioperative period. Methods: Probiotic-derived vesicles (pbMVs) were administered postoperatively. pbMVs were isolated and characterized from probiotics, mainly from the bacteria genus Lactobacillus, Bifidobacterium, and Lactococcus. Mice underwent bile duct ligation, sham laparotomy (SHAM), or 70% partial hepatectomy (70%PH). pbMVs were tracked in vivo, and intrahepatic cellular and molecular aspects were analyzed by flow cytometry and qRT-PCR techniques. Liver sinusoidal endothelial cells (LSECs) analysis for Vascular Cell Adhesion Molecule-1(VCAM-1) expression following pbMV stimulation of cultured liver non-parenchymal cells which had been activated by LPS. Results: The administered pbMV rapidly translocated to the liver after surgery. pbMV administrations following surgeries enhanced neutrophil clearance; there was a dramatic decline in the liver neutrophil-to-lymphocyte ratio Ly6G+/CD3+ and an increase in IL6 levels. pbMVs reduced intrahepatic VCAM1 and ICAM2 expression compared with control following SHAM and decrease in IL10 levels following 70%PH. The administration of pbMV improved liver regeneration 72 hours following surgical liver resection with a significant decrease in IL17 expression. pbMVs modulated VCAM-1 on liver sinusoidal endothelial cells in liver cell culture. Conclusions: Our study findings provide mechanistic insights into the liver-gut axis following surgery and illustrate how probiotic vesicles can reduce adhesion molecule expression and affect immune cell invasion and liver immunity, resulting in improved liver recovery following hepatic surgery.

Background: The risk of recurrence after hepatectomy for colorectal liver metastasis (CRLM) remains high. The objective of the current study was to develop a novel online calculator to estimate the risk of CRLM recurrence using pathological, genetic, and morphologic tumor characteristics. Methods: Patients who underwent hepatectomy for CRLM between 2001-2018 were identified from a multi-institutional international database. A prognostic model was developed in the training set and validated using an external cohort. Patients were categorized into three risk groups (low, intermediate, and high-risk) based on the model score. An online calculator to estimate 1, 3, 5-year recurrence free survival (RFS) was developed and compared with the clinical risk score (CRS) using Harell's c-index. Results: Among 1,125 patients who underwent CRLM resection, median tumor number was 2 (IQR, 1-3) and median tumor size was 3.0cm (IQR, 2.0-5.0). Median CEA level was 9.9 ng/mL (IQR, 3.8-44.8), while a subset of patients presented with synchronous disease (n=792, 70.4%). On pathology, one-third of patients had mtKRAS (n=343, 30.4%), while 69.6% (n=782) had wtKRAS. Overall 1-, 3-, 5-year RFS was 61.1%, 33.9%, and 28.1 %, respectively. The CRS performed relatively poorly with a