Laparoscopic central hepatectomy using a parenchymal-first approach: how we do it.

BACKGROUND: Laparoscopic central hepatectomy (LCH) is a difficult and challenging procedure. This study aimed to describe our experience with LCH using a parenchymal-first approach. METHODS: Between July 2017 and June 2021, 19 consecutive patients underwent LCH using a parenchymal-first approach at our institution. Herein, the details of this procedural strategy are described, and the demographic and clinical data of the included patients were retrospectively analyzed. RESULTS: There were 1 female and 18 male patients, all with hepatocellular carcinoma without major vascular invasion. The mean age was 57 ± 10 years. No patients underwent conversion to open surgery, and no blood transfusions were needed intraoperatively. The average operative duration and the average Pringle maneuver duration were 223 ± 65 min and 58 ± 11 min. respectively. The median blood loss was 200 ml (range: 100-800 ml). Postoperative morbidities occurred in 3 patients (15.8%), including 2 cases of bile leakage and 1 case of acquired pulmonary infection; there were no postoperative complications happened such as bleeding, hepatic failure, or mortality. The average postoperative hospital stay was 10 ± 3 days. CONCLUSION: The optimized procedure of LCH using a parenchymal-first approach is not only feasible but also expected to provide an advantage in laparoscopic anatomical hepatectomy.

Ceramides and sphingosine-1-phosphate mediate the distinct effects of M1/M2-macrophage infusion on liver recovery after hepatectomy.

Post-hepatectomy liver dysfunction is a life-threatening morbidity that lacks efficient therapy. Bioactive lipids involved in macrophage polarization crucially regulate tissue injury and regeneration. Herein, we investigate the key bioactive lipids that mediate the cytotherapeutic potential of polarized-macrophage for post-hepatectomy liver dysfunction. Untargeted lipidomics identified elevation of ceramide (CER) metabolites as signature lipid species relevant to M1/M2 polarization in mouse bone-marrow-derived-macrophages (BMDMs). M1 BMDMs expressed a CER-generation-metabolic pattern, leading to elevation of CER; M2 BMDMs expressed a CER-breakdown-metabolic pattern, resulting in upregulation of sphingosine-1-phosphate (S1P). After infusing M1- or M2-polarized BMDMs into the mouse liver after hepatectomy, we found that M1-BMDM infusion increased M1 polarization and CER accumulation, resulting in exaggeration of hepatocyte apoptosis and liver dysfunction. Conversely, M2-BMDM infusion enhanced M2 polarization and S1P generation, leading to alleviation of liver dysfunction with improved hepatocyte proliferation. Treatment of exogenous CER and S1P or inhibition CER and S1P synthesis by siRNA targeting relevant enzymes further revealed that CER induced apoptosis while S1P promoted proliferation in post-hepatectomy primary hepatocytes. In conclusion, CER and S1P are uncovered as critical lipid mediators for M1- and M2-polarized BMDMs to promote injury and regeneration in the liver after hepatectomy, respectively. Notably, the upregulation of hepatic S1P induced by M2-BMDM infusion may have therapeutic potential for post-hepatectomy liver dysfunction.

The preventive effect of Chinese herbal preparation Xuebijing against hyperactive inflammation after hepato-pancreato-biliary surgery.

BACKGROUND: Hepato-pancreato-biliary (HPB) surgery is a primary treatment for benign and malignant diseases of the liver, biliary tract, and pancreas. Hyperactive inflammation has been indicated as a critical risk factor of post-operation death after HPB surgery. Xuebijing is an anti-inflammatory intravenous herbal preparation made from traditional Chinese medicines. Emerging evidence has implicated a protective role of Xuebijing against hyperactive inflammation. METHODS: A retrospective cohort study was conducted. We analyzed a total of 638 cases of HPB surgery, including hepatectomy, Whipple's surgery, and surgeries for cholelithiasis, which were divided into a Xuebijing treatment group and a conventional treatment group according to whether they were treated with Xuebijing injection or not. Clinical data related to liver function and inflammation were compared between the two groups after operation, including liver function index, white blood cell (WBC) count, neutrophil percentage (NE%), C-reactive protein (CRP), serum interleukin-6 (IL-6), body temperature, mortality, incidence of adverse reaction, length of postoperative hospital stay, and hospitalization cost. RESULTS: Xuebijing injection was found to decrease the levels of inflammatory markers in the blood significantly, including WBC, NE%, CRP, IL-6, and reduce the incidence of postoperative fever without prolonging in-hospital length or increasing cost compared to the conventional treatment group. Moreover, our data demonstrated that Xuebijing injection did not impact liver function after hepatectomy. CONCLUSIONS: These results suggest that Xuebijing injection alleviates hyperactive inflammation caused by HPB surgery, and support the application of Xuebijing injection as a safe therapeutic approach against hyperactive inflammation in patients with HPB surgery.

Prediction and analysis of weighted genes in hepatocellular carcinoma using bioinformatics analysis.

The aim of the present study was to identify the differentially expressed genes (DEGs) between primary tumor tissue and adjacent non­tumor tissue of hepatocellular carcinoma (HCC) samples in order to investigate the mechanisms of HCC. The microarray data of the datasets GSE76427, GSE84005 and GSE57957 were downloaded from the Gene Expression Omnibus database. DEGs were identified using the limma package in the R programming language. Following the intersection of the DEGs screened from the three datasets, 218 genes were selected for further study. A protein­protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes database. The construction and analysis of modules were performed using Cytoscape and the module with the highest score was selected for further analysis. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted for genes involved in the PPI network and the selected subnetwork. The network of the enriched pathways and their associated genes was constructed using Cytoscape. For the genes in the global PPI network, metabolism­associated pathways were significantly enriched; whereas, for the genes in the subnetwork, 'cell cycle', 'oocyte meiosis' and 'DNA replication' pathways were significantly enriched. To demonstrate the portability and repeatability of the prognostic value of the weighted genes, a validation cohort was obtained from datasets of The Cancer Genome Atlas and Kaplan­Meier survival analysis was conducted. Evidence is presented that the expression levels of aldehyde dehydrogenase 2 family member, cytochrome P450 family 2 subfamily C member 8, alcohol dehydrogenase 4 (class II), pi polypeptide, alcohol dehydrogenase 1B (class I), ß polypeptide and cytochrome P450 family 2 subfamily C member 9 were associated with the overall survival of patients with HCC and that the expression levels of pituitary tumor­transforming 1, cell division cycle 20, DNA topoisomerase II α and cyclin B2 were negatively associated with the overall survival of patients with HCC. In conclusion, 9 weighted genes, involved in the development and progression of HCC, were identified using bioinformatics and survival analyses.

[Effect of Xuebijing injection on postoperative inflammatory response in patients after hepatobiliary and pancreatic surgeries: a retrospective cohort study].

OBJECTIVE: To analyze the effect of Xuebijing injection on inflammatory response in patients after hepatobiliary and pancreatic surgeries, and to evaluate its safety and clinical value. METHODS: A retrospective cohort study was conducted. 708 patients received hepatobiliary and pancreatic surgeries of Nanfang Hospital, Southern Medical University from January 2015 to September 2017 were enrolled and divided into Xuebijing treatment group and conventional treatment group according to whether they were treated with Xuebijing injection or not. The inflammatory response indexes included white blood cell count (WBC), neutrophil (NE), C-reactive protein (CRP), body temperature, which were compared between the two groups at 1, 3, and 5 days after operation. The incidence of adverse reactions, the length of postoperative hospital stays and hospitalization costs were compared. RESULTS: A total of 209 patients were prescribed with Xuebijing injection, and 499 patients were allocated into conventional treatment group. The two groups were stratified by liver, biliary and pancreatic surgery types, and further 1:1 propensity score matching was performed. After propensity score match, 189 patients were included in each group, with 101, 46, and 42 patients undergoing liver, biliary, and pancreas surgery, respectively. There were no significant differences in baseline data such as gender, age and inflammatory response indexes before surgery between the two groups. In both groups, the WBC and NE showed a gradual decline after operation, CRP were increased gradually and then decreased after 3 days. Compared with the conventional treatment group, Xuebijing treatment group showed obvious anti-inflammatory effect from 3 days after operation [WBC (×109/L): 10.1±4.0 vs. 11.0±3.5, NE: 0.71±0.10 vs. 0.76±0.12, CRP (mg/L): 73.1±38.7 vs. 82.2±41.8, all P < 0.05]. On the 5th day, it still showed a strong anti-inflammatory trend [WBC (×109/L): 7.0±2.8 vs. 7.9±2.6, NE: 0.62±0.10 vs. 0.68±0.12, CRP (mg/L): 43.4±31.0 vs. 50.9±25.3, all P < 0.05]. The cases of postoperative fever in the Xuebijing treatment group were significantly less than that in the conventional treatment group (cases: 98 vs. 119, χ2 = 4.711, P = 0.029). There was no significant different in the total incidence of adverse drug reactions such as rash, nausea and vomiting (5.0% vs. 3.2%), the length of postoperative hospital stays [days: 9.3 (6.1, 13.5) vs. 9.1 (5.5, 13.3)] and hospitalization costs [wanyuan: 5.8 (3.6, 9.5) vs. 5.7 (3.5, 9.8)] between Xuebijing treatment group and conventional treatment group (all P > 0.05). CONCLUSIONS: Xuebijing injection has a good anti-inflammatory effect on patients undergoing hepatobiliary and pancreatic surgeries. Xuebijing injection has good safety and can be applied to the prevention and treatment of excessive inflammatory reaction after hepatobiliary and pancreatic surgeries.

Expression of Allograft Inflammatory Factor-1 (AIF-1) in Hepatocellular Carcinoma.

BACKGROUND Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein cloned from activated macrophages in human and rat allografts. AIF-1 has been identified as a modulator of inflammatory response, and recently published studies have shown its increased expression in carcinogenesis. However, there are still limited data on the potential functional role of AIF-1 in hepatocellular carcinoma (HCC). MATERIAL AND METHODS We evaluated the expression of AIF-1 in 104 cases of paired HCC and adjacent non-cancerous liver tissues using immunohistochemistry, Western blotting, and qPCR analysis, and sought to determine whether its expression was correlated with clinicopathological features. In vitro assays, including cell proliferation and migration assays, were used to study the effects of AIF-1 knockdown in L02 human hepatocyte, and Huh7 and SMMC7721 liver cancer cell lines. RESULTS Expression of AIF-1 was increased in HCC compared to adjacent normal liver tissues and was positively correlated with median tumor size (p=0.046), number of tumor deposits (p=0.009), the Barcelona Clinic Liver Cancer (BCLC) stage (p=0.004), and portal vein tumor thrombus (PVTT) (p<0.001). Huh7 and SMMC7721 human HCC cells demonstrated upregulated AIF-1 expression compared to normal hepatocytes. Small interfering RNA (siRNA)-mediated silencing of AIF-1 expression resulted in a reduction in cell proliferation and migration in human HCC cells. CONCLUSIONS These findings suggest AIF-1 may have roles as a diagnostic or prognostic biomarker and a promising therapeutic target in HCC.