BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

Humans ; Carcinoma, Hepatocellular/surgery* ; Liver Neoplasms/pathology* ; Cholangiocarcinoma/pathology* ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/pathology*

Recurrence of hepatocellular carcinoma (HCC) after surgery is a major factor affecting the efficacy of the treatment of patients. Neoadjuvant treatment is an effective therapeutic method to reduce postoperative recurrence and prolong patient survival. However,there is no generally accepted neoadjuvant treatment regimen that has been proven to be effective so far. Recently,with the progress in systemic antitumor therapies,represented by targeted molecular agents and immune checkpoint inhibitors,and the improvement in local regional therapies,these treatment approaches have shown promising efficacy and safety in the field of neoadjuvant treatment for HCC. Under the organizational leadership of Committee of Digestive Surgery of Chinese Research Hospital Association and Committee of Liver Cancer of Chinese Anti-Cancer Association,Alliance of Chinese Expert Consensus on Neoadjuvant Therapy for Hepatocellular Carcinoma has discussed and revised several times and finally formulated the Chinese expert consensus on neoadjuvant therapy for hepatocellular carcinoma (2023 edition). This consensus aimed to review the Chinese characteristics of the diagnosis and treatment of HCC,to provide specific guidance and suggestions for preoperative treatment strategies for HCC,and further promote the management of the clinical pathway for neoadjuvant treatment of HCC.
Humans ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/surgery* ; China ; Consensus ; Liver Neoplasms/pathology* ; Neoadjuvant Therapy

Clinical practice using associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) or its modified procedures in treatment of primary hepatocellular carcinoma(HCC) with insufficient future liver remnant(FLR) in the past 10 years has failed to meet our expectations both in achieving decreased perioperative complications and mortality.The efficacy of ALPPS in improving long-term survival outcome of HCC still remains poor.Due to the trauma of two surgery within a short period,and patients with inadequate FLR are all diagnosed at advanced disease stages,ALPPS can only achieve surgical rather than biological tumor-curability.Previous studies have demonstrated comparable 5-year survival rates between early and advanced stages of HCC who underwent regional treatments.Therefore,tumor biological conversion is the key strategy prior to liver remnant volume conversion in improving treatment outcomes for HCC patients with insufficient FLR.Target therapy,immunotherapy together with locally treatment were expected to improve the conversion efficacy.Looking back at the development of ALPPS for the last decade,the rapid proliferation of FLR should be passed on,while the technology costs high risks and result in poor long-term outcome must be cautiously selected.
Carcinoma, Hepatocellular/surgery* ; Hepatectomy ; Humans ; Ligation ; Liver ; Liver Neoplasms/surgery* ; Portal Vein/surgery* ; Technology ; Treatment Outcome

Objective: To investigate the clinical value of the bipolar tweezers-clamp for the hepatic parenchymal transection in the resection of hepatocellular carcinoma. Methods: From January 2020 to January 2021,63 patients with the hepatocellular carcinoma for hepatectomy at Department of Hepatopancreatobiliary Surgery,Yuebei People's Hospital Affiliated to Shantou University Medical College were analyzed retrospectively.According to the different instruments used in the hepatic parenchymal transection,the patients were divided into bipolar tweezers-clamp group and ultrasonic scalpel group.There were 32 patients in bipolar tweezers-clamp group,with age of (55.5±10.5)years(range:37 to 78 years),including 22 males and 10 females,tumor size was (6.0±3.4)cm(range:2.4 to 13.4 cm). There were 6 patients with portal vein tumor thrombus and 5 patients with portal hypertension. There were 31 patients in ultrasonic scalpel group,with aged(57.8±10.1)years(range:37 to 79 years),including 27males and 4 females,tumor size was(7.9±5.1)cm(range: 2.4 to 21.3 cm),3 patients with portal vein tumor thrombus and 2 patients with portal hypertension. The preoperative baseline data,operation time,blood loss,postoperative liver function and the complications were compared between two groups using t test,χ² test and Fisher exact probabilityrespectively. Results: The operation was successfully completed in both groups.Compared with the ultrasonic scalpel group,the operation time was significantly shorter((219.3±76.4)minutes vs.(294.0±100.8)minutes,t=-3.322,P=0.002),the blood loss was less((250(475)ml vs. 500(1 050)ml,t=-2.307,P=0.026),the concentrate red blood cells transfusion volume was less(0.92(0.88)U vs. 2.32(4.00)U,Z=-1.987,P=0.047) in the bipolar tweezers-clamp group.The postoperative serum ALB level was higher in the bipolar tweezers-clamp group than that in the ultrasonic scalpel group((33.5±6.1)g/L vs. (29.5±4.2)g/L,t=3.226,P=0.020) on postoperative day 1;((35.7±4.5)g/L vs.(30.1±3.2)g/L,t=5.575,P<0.01) on postoperative day 3;((33.2±3.7)g/L vs. (31.0±4.4)g/L,t=3.020,P=0.004) on postoperative day 7. There was no significant difference in serum ALT,TBIL and PT level between the two groups(all P>0.05).No postoperative bile leakage occurred in both groups.The postoperative complications occurred in 8 cases(25.0%)in the bipolar tweezers-clamp group,including liver failure in one,and in 11 cases(35.5%)in the ultrasonic scalpel group,including liver failure in two(P>0.05). Conclusion: The bipolar tweezers-clamp is a safe and reliable method for the hepatic parenchymal transaction,which is quick and less bleeding during the hepatic resection.
Blood Loss, Surgical ; Carcinoma, Hepatocellular/surgery* ; Female ; Hemorrhage ; Hepatectomy/methods* ; Humans ; Hypertension, Portal/surgery* ; Liver Failure ; Liver Neoplasms/surgery* ; Male ; Retrospective Studies ; Treatment Outcome

Humans ; Carcinoma, Hepatocellular/secondary* ; Liver Neoplasms/surgery* ; Thyroid Neoplasms/surgery* ; Neoplasms, Second Primary

Surgical resection (SR) is recommended as a radical procedure in the treatment of hepatocellular carcinoma (HCC). However, postoperative recurrence negatively affects the long-term efficacy of SR, and preoperative adjuvant therapy has therefore become a research hotspot. Some clinicians adopt transcatheter arterial chemoembolization (TACE) as a preoperative adjuvant therapy in patients undergoing SR to increase the resection rate, reduce tumor recurrence, and improve the prognosis. However, the findings of the most relevant studies remain controversial. Some studies have confirmed that preoperative TACE cannot improve the long-term survival rate of patients with HCC and might even negatively affect the resection rate. Which factors influence the efficacy of preoperative TACE combined with SR is a topic worthy of investigation. In this review, existing clinical studies were analyzed with a particular focus on several topics: screening of the subgroups of patients most likely to benefit from preoperative TACE, exploration of the optimal treatment regimen of preoperative TACE, and determination of the extent of tumor necrosis as the deciding prognostic factor.
Carcinoma, Hepatocellular/surgery* ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Hepatectomy ; Humans ; Liver Neoplasms/surgery* ; Neoplasm Recurrence, Local

BACKGROUND: Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. METHODS: Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. RESULTS: The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS. CONCLUSIONS Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.
Antiviral Agents/therapeutic use* ; Carcinoma, Hepatocellular/surgery* ; Guanine/analogs & derivatives* ; Hepatectomy ; Hepatitis B virus ; Hepatitis B, Chronic/drug therapy* ; Humans ; Liver Neoplasms/surgery* ; Retrospective Studies ; Tenofovir/therapeutic use*

BACKGROUND: The clinical trials emerged centromere protein E inhibitor GSK923295 as a promising anticancer drug, but its function in hepatocellular carcinoma (HCC) remain needs to be fully elucidated, especially as chemotherapy after hepatectomy for liver tumors. We aimed to describe anti-HCC activities of GSK923295 and compare its antiproliferative effects on liver regeneration after partial hepatectomy (PH). METHODS: All subjects were randomized to treatment with either vehicle or GSK923295. Antitumor activity of GSK923295 was assessed by xenograft growth assays. The C57BL/6 mice were subjected to 70% PH and the proliferation was calculated by liver coefficient, further confirmed by immunohistochemistry. The proliferation and cell cycle analysis of liver cell AML12 and HCC cells LM3, HUH7, and HepG2 were investigated using the cell counting kit-8 assay and Flow Cytometry. The chromosome misalignment and segregation in AML12 cells were visualized by immunofluorescence. RESULTS: Treatment with GSK923295 induced antiproliferation in HCC cell lines. It also caused delay on HCC tumor growth instead of regression both in a HCC cell line xenograft model and patient-derived tumor xenograft model. With microarray analysis, CENtromere Protein E was gradually increased in mouse liver after PH. Exposure of liver cells to GSK923295 resulted in delay on a cell cycle in mitosis with a phenotype of misaligned chromosomes and chromosomes clustered. In 70% PH mouse model, GSK923295 treatment also remarkably reduced liver regeneration in later stage, in parallel with the mitotic marker phospho-histone H3 elevation. CONCLUSION The anticancer drug GSK923295 causes a significant delay on HCC tumor growth and liver regeneration after PH in later stage.
Animals ; Antineoplastic Agents ; therapeutic use ; Blotting, Western ; Bridged Bicyclo Compounds, Heterocyclic ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; surgery ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Chromosomal Proteins, Non-Histone ; antagonists & inhibitors ; Electrophoresis, Polyacrylamide Gel ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Liver Neoplasms ; drug therapy ; surgery ; Liver Regeneration ; physiology ; Mice ; Mice, Inbred C57BL ; Real-Time Polymerase Chain Reaction ; Sarcosine ; analogs & derivatives ; therapeutic use ; Xenograft Model Antitumor Assays

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. Liver transplantation (LT) is known as a curative and therapeutic modality. However, the survival rates of recipients after LT are still not good enough because of tumor recurrence. To improve the survival rates of recipients after LT, identifying predictive factors for prognosis after LT and establishing a model assessing prognosis are very important to HCC patients. There has recently been a lot of clinical and basic research on recurrence and prognosis after LT. Progress has been made, especially in selection criteria for LT recipients and risk factors for predicting prognosis after LT. Hangzhou criteria, in line with China's high current incidence rate of primary liver, are first proposed by Chinese scholars of LT, and are accepted world-wide, and make an important contribution to the development of LT.
Carcinoma, Hepatocellular ; mortality ; surgery ; China ; epidemiology ; Humans ; Liver Neoplasms ; mortality ; surgery ; Liver Transplantation ; Neoplasm Recurrence, Local ; mortality ; Patient Selection ; Prognosis ; Risk Factors ; Survival Rate