Advances in post-operative prognostic models for hepatocellular carcinoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Surgery remains the primary and most successful therapy option for the treatment of early- and mid-stage HCCs, but the high heterogeneity of HCC renders prognostic prediction challenging. The construction of relevant prognostic models helps to stratify the prognosis of surgically treated patients and guide personalized clinical decision-making, thereby improving patient survival rates. Currently, the prognostic assessment of HCC is based on several commonly used staging systems, such as Tumor-Node-Metastasis (TNM), Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer (BCLC). Given the insufficiency of these staging systems and the aim to improve the accuracy of prognostic prediction, researchers have incorporated further prognostic factors, such as microvascular infiltration, and proposed some new prognostic models for HCC. To provide insights into the prospects of clinical oncology research, this review describes the commonly used HCC staging systems and new models proposed in recent years.

Risk factors of intrahepatic recurrence after resection for Barcelona Clinic Liver Cancer stage 0 hepatocellular carcinoma / 中华肝胆外科杂志

Objective To investigate the risk factors of intrahepatic recurrence after resection for Barcelona Clinic Liver Cancer (BCLC) stage 0 hepatocellular carcinoma (HCC).Methods 58 patients with pathologically confirmed BCLC stage 0 HCC treated with liver resection at the Zhongshan Hospital,Fudan University from January to December 2011 were included in this study.The male/female ratio was 50/8.The age ranged from 31 to 72 years.The clinical,pathological and MR imaging features of these patients were analyzed.The recurrence-free survival rates between patients with HCC ≤ 1.5 cm (n=27) and ＞ 1.5 cm (n=31) were compared.The risk factors of intrahepatic recurrence for HCCs were compared using the Cox regression analysis.Results Intrahepatic recurrence was identified in 25 patients,and the median recurrence time was 33 months.The 3-and 5-year cumulative recurrence-free survival rates were 73.0％ (95％CI:60.7％～85.3％) and 52.3％ (95％CI:37.2％～67.4％).No significant differences were found in the recurrence-free survival rates between tumors ≤ 1.5 cm and ＞ 1.5 cm (P＞0.05).Multivariate analyses demonstrated that serum alpha-fetoprotein level ＞20 g/L (HR 3.773,95％CI:1.628～8.745;P＜0.05) and irregular tumor shape (HR 4.584,95％CI:1.485～ 14.155;P＜0.05) were independent risk factors of intrahepatic recurrence.Conclusions Elevated serum alpha-fetoprotein level and irregular tumor shape were associated with an increased risk of intrahepatic recurrence for BCLC stage 0 HCC patients after resection.They could be used as early prognostic indicators in clinical practice.

Hepatectomy combined with splenectomy in patients with hepatocellular carcinoma with Barcelona Clinic Liver Cancer Stage A and portal hypertension / 中华肝胆外科杂志

Objective To evaluate the peri-operative and survival outcomes of hepatectomy combined with splenectomy in patients with hepatocellular carcinoma with Barcelona Clinic Liver Cancer Stage A and portal hypertension.Methods We retrospectively analyzed the data on patients with hepatocellular carcinoma with Barcelona Clinic Liver Cancer Stage A and portal hypertension who underwent surgery at the Shengli Oilfield Central Hospital between July 2008 and June 2015.According to the operative method,the patients were classified as the experimental group (hepatectomy combined with splenectomy) and the control group (hepatectomy).We compared and analyzed the clinical data between these two groups,which included the operation time,blood loss,duration of hepatic portal occlusion,width of surgical resection margin,liver function,PLT,HBV reactivation,time to remove drainage tube,complications,upper gastrointestinal hemorrhage rate and survival outcomes.Results (1) The operation time,blood loss,PLT at 1 week and 1 month after surgery in the experimental group were all significantly higher than the control group [(161.4 ± 38.3) min vs.(119.2±36.4) min,(268.7±72.1) vs.(201.3±61.3) ml,(189.2±51.3) ×109/L vs.(81.9±32.2) ×109/L,(327.4±69.1) ×109/L vs.(84.5±28.5) × 109/L (all P＜0.05),respectively].The time to remove drainage tube,duration of hepatic portal occlusion,width of resection surgical margin,TBil,complications and upper gastrointestinal hemorrhage rates of the two groups were not significantly different (all P ＞ 0.05).The HBV reactivation rate,ALT and AST in the experimental group were significantly lower than the control group [3.9％ (2/51) vs.18.2％ (12/66),(45.7 ± 11.4) U/L vs.(58.3±14.7) U/L,(48.1±12.4) U/Lvs.(61.3±15.1) U/L (allP＜0.05),respectively].(2) The 1,3 and 5-year recurrence free survival rates were not significantly different between the experimental and control groups [84.3 ％,34.1％,27.3 ％ vs.78.8 ％,42.1％,9.7 ％ (all P ＞ 0.05),respectively].The 1,3 and 5-year overall survival rates in the experimental Group were significantly higher than the control group [94.1％,66.3 ％,33.5 ％ vs.90.9％,46.7％,16.1％ (all P ＜ 0.05),respectively].Conclusion Combined liver and spleen resection was a safe and efficacious modality to treat patients with BCLC A hepatocellular carcinoma,which reduced the incidence of HBV reactivation and improved the overall survival.

Prognostic and subgroup analysis of 162 patients with Barcelona Clinical Liver Cancer (BCLC)stage B hepatocellular carcinoma after hepatectomy / 中华肝胆外科杂志

Objectives To analyze prognosis and risk factors of Barcelona Clinical Liver Cancer (BCLC) stage B hepatocellular carcinoma patients treated with hepatectomy.Methods Clinical data of 162 BCLC stage B patients who underwent hepatectomy at Tianjin Medical University Cancer Institute & Hospital and the Second Hospital of Tianjin Medical University from June 2007 to December 2013 were retrospectively studied.The correlations between factors (age,gender) and long-term outcome were analyzed to determine independent risk factors.Subsequently,subgroup analysis of BCLC stage B hepatocellular carcinoma was performed.Results Multiple tumors,maximum tumor diameter ＞ 10 cm and AFP ＞ 100 μg/L were con firmed as independent risk factors of overall survival in postoperative BCLC B patients.Based on the risk factors,patients were divided into two groups,namely low-risk subgroup (≤ 1 risk factor) and high-risk subgroup (≥ 2 risk factors).In low-risk subgroup,1,3 and 5-year overall survival (OS) rates were 91.6％,65.5％,61.9％ respectively,and mean OS was 72 months.By contrast,1,3 and 5-year OS rates in high-risk subgroup were 67.4％,25.6％,10.8％ respectively,and mean OS was 29 months.Further more,1,3 and 5-year OS rates of all patients were 85.2％,54.9％,48.0％ respectively,and mean OS was 61 months.Conclusions Relatively favorable long-term outcomes could be yielded in BCLC stage B hepatocellular carcinoma patients treated with liver resection.The independent risk factors including multiple tumors,maximum tumor diameter ＞ 10 cm and AFP ＞ 100 μg/L were closely correlated with overall survival.BCLC stage B hepatocellular carcinoma patients could be divided into low-risk and high-risk subgroups based on the risk factors mentioned above.Survival rates in low-risk subgroup are remarkably superior to those in high-risk subgroup.

Surgical Perspectives of Hepatocellular Carcinoma beyond the Barcelona Clinical Liver Cancer Guideline; Focusing on Liver Transplantation

The management of hepatocellular carcinoma (HCC) is decided according to the evidence base recommendations generated by international societies especially by Barcelona clinical liver cancer (BCLC) guideline. However, the BCLC guideline based on studies of the Western countries, has not been well matched to real life cohort in Korea. In Western countries, a deceased donor liver transplantation has been well allocated to the HCC patients with preserved liver function. Patients with mild to moderate portal hypertension and certain BCLC B patients could be eligible for hepatic resection if a chance for 50% survival rate at 5 years is perceived. If liver transplantation (LT) is back up for liver resection in those patients as a salvage therapy, widening indication of liver resection could be much easily acceptable. On the other hands, new selection criteria of HCC beyond Milan criteria considering tumor biology, has been provided in the field of LT resulting in more than 50% survival rate at 5 years. Herein, surgical perspectives beyond the BCLC recommendation for LT for HCC would be reviewed in the respect of Korean surgeon's view in this article.

Clinical staging and treatment strategy for hepatocellular carcinoma / 国际外科学杂志

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death worldwide.Increase in incidence has been shown in HCC over the last few years and more than half of the cases were reported in China,where hepatitis B virus (HBV) infection is the main etiologic factor.Heterogeneity in HCC's distribution worldwide and difference in etiology may result in a more complicated issue about prognosis-estimation and choosing of treatment options for HCC patients.In the past decade,there have been several clinical staging systems developed in terms of relevant prognostic factors.Among them,the Barcelona Clinic Liver Cancer (BCLC) and the Hong Kong Liver Cancer (HKLC) staging system are the only two classifications that link prognostic classification to treatment indications.In this review,we mainly focus on the application of BCLC and HKLC staging systems in guiding decision making for HCC,the respective advantages and disadvantages of each classification,and the future perspective of our own prediction model in which some new clinical factors will be integrated.

Applicability of the BCLC staging system to patients with hepatocellular carcinoma in Korea: analysis at a single center with a liver transplant center / 대한간학회지

BACKGROUND/AIMS: The Barcelona Clinic Liver Cancer (BCLC) staging system is logical for the staging and treatment of hepatocellular carcinoma (HCC) because it was based on survival data. This study evaluated the applicability of the BCLC staging system and reasons for divergence from BCLC-recommended treatments in Korean HCC patients. METHODS: One hundred and sixty consecutive HCC patients were prospectively enrolled. Treatments were generally recommended according to the guideline of the American Association for the Study of Liver Diseases, but patients were also informed about alternative treatments. The final decision was made with patient agreement, and was based on the doctor's preferences when a patient was unable to reach a decision. RESULTS: There were 2 (1%), 101 (64%), 20 (12.5%), 34 (21.5%), and 3 (1%) patients with very early-, early-, intermediate-, advanced-, and terminal-stage disease, respectively. Only 64 patients (40%) were treated according to BCLC recommendations. The treatment deviated from BCLC recommendations in 68% (69/101) and 79% (27/34) of patients with early and advanced stage, respectively. The main causes of deviation were refusal to undergo surgery, the presence of an indeterminate malignancy nodule, the absence of a suitable donor, or financial problems. CONCLUSIONS: Donor shortage, financial problems, the relatively limited efficacy of molecular targeting agents, and the presence of an indeterminate nodule were the main causes of deviation from BCLC recommendations. Even after excluding cases in which decisions were made by patient preference, only 66% of the HCC patients were treated according to BCLC recommendations. Treatment guidelines that reflect the Korean situation are mandatory for HCC patients.

Are Surgical Indications of Barcelona Clinic Liver Cancer Staging Classification justified? / 华中科技大学学报（医学）（英德文版）

Liver resection is the most effective treatment for hepatocellular carcinoma (HCC).The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly accepted as a guideline for HCC treatment,but it only recommends liver resection for the patients with HCC at stage 0 to A1.The surgical indications of the BCLC staging system need to be re-evaluated.120 HCC patients undergoing curative liver resection were retrospectively stratified to the BCLC staging system,and the survival of the patients at stages A,B and C was analyzed.The justification of the BCLC staging system was re-evaluated.Fifty-two patients were classified at stage A,51 at stage B and 17 at stage C respectively.The hospital mortality of this cohort was zero and the morbidity was 24.1％.The 1-,2-,3-year overall survival rate of this cohort was 81.6％,68.3％,and 57.5％ respectively.There was no significant difference in the survival rate between the patients at stage A and B (P＞0.05).If the treatment guidelines of BCLC staging system were followed,the majority of the patients at stages A and B (77.7％,80/103) would not have been treated surgically.Our data suggest that the surgical indications of the BCLC staging system are not justified for HCC treatment.More studies may be needed as for how to further broaden the surgical indications of the BCLC staging system in the future.

Comparison of 7 staging systems in north Indian cohort of hepatocellular carcinoma.

Background & Aim: Many liver staging systems have been proposed for patients with hepatocellular carcinoma (HCC); however it is still controversial which staging system is best. The aim of this study was to compare the ability of 7 different staging systems in predicting survival in an Indian cohort of patients with HCC. Methods: In this prospective study, 101 HCC patients were diagnosed and stratified according to 7 different staging systems; along with analysis of independent predictors of survival and their correlation with it (Kaplan-Meier analysis). Results: CLIP, Tokyo score and BCLC staging system showed a significant difference in the probability of survival. All other staging systems failed to show a significant difference in survival. Age, portal vein thrombosis, serum bilirubin, MELD score showed a significant difference with survival in univariate analysis. However, serum bilirubin was the independent predictor of survival with a hazard ratio of 1.609 (95% CI 1.015-2.553, p= 0.043). Conclusion: The CLIP, Tokyo score and BCLC are the most useful staging systems in an Indian cohort.