Jia-Zhou Ye

Appropriate treatment strategies improve survival of hepatocellular carcinoma patients with portal vein tumor thrombus

AIM To evaluate the survival benefits of different treatment strategies for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to determine the prognosis factors. METHODS Between 2007 and 2009, 338 HCC patients treated for PVTT were retrospectively studied. The patients were divided into 4 groups that underwent different treatments: the conservative treatment group (n = 75), the transarterial chemoembolization (TACE) group (n = 86), the hepatic resection group (n = 90), and the hepatic resection associated with postoperative TACE group (n = 87). Survival rates were determined using the Kaplan-Meier method and differences between the groups were identified through log-rank analysis. Coxs proportional hazard model was used to identify the risk factors for survival. RESULTS The mean survival periods for patients in the conservative treatment, TACE, hepatic resection and hepatic resection associated with postoperative TACE groups were 3.8, 7, 8.2 and 15.1 mo, respectively. Significant differences were observed in the survival rates. For the surgical resection associated with postoperative TACE group, the survival rates after 1, 2 and 3 years were 49%, 37% and 19%, respectively. These results were significantly higher than those of the other groups (P < 0.05). Meanwhile, the 1, 2 and 3 year survival rates for the surgical resection group were 28%, 20% and 15%, whereas those for the TACE group were 17.5%, 0% and 0%, respectively. These values significantly increased after hepatic resection compared with those after TACE (P < 0.05). CONCLUSION Surgical resection is the most effective therapeutic strategy for HCC patients with PVTT and results in high hepatic functional reserve. For patients who can tolerate the procedure, postoperative TACE is necessary to prevent recurrence and prolong the survival period.

Lymphocyte to monocyte ratio and neutrophil to lymphocyte ratio are superior inflammation‐based predictors of recurrence in patients with hepatocellular carcinoma after hepatic resection

The purpose of this study was to investigate which inflammation‐based marker more accurately predict recurrence in patients receiving hepatectomy for hepatocellular carcinoma (HCC).

Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion

AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer (BCLC) early (A) and intermediate (B) stage hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). METHODS A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival (RFS) and overall survival (OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE. RESULTS Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/mL, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/mL, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/mL, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE. CONCLUSION PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early- and intermediate-stage HCC patients with MVI.

High expression of AKR1B10 predicts low risk of early tumor recurrence in patients with hepatitis B virus-related hepatocellular carcinoma.

To clarify the relationship between aldo-keto reductase family 1 member B10 (AKR1B10) expression and early hepatocellular carcinoma (HCC) recurrence, this study detected AKR1B10 expression in tumor and adjacent non-tumor tissues from 110 patients with hepatitis B virus (HBV)-related HCC underwent liver resection and analyzed its correlations with clinicopathological characteristics and prognosis of these patients. Detected by quantitative reverse transcription polymerase chain reaction, AKR1B10 mRNA expression showed significantly higher in HCC tissues than in adjacent non-tumor tissues, with a low level in normal liver tissues. Similar results was confirmed at the protein level using immunohistochemistry and Western blotting. High AKR1B10 expression was negatively correlated with serum alpha-fetoprotein level and positively correlated with HBV-DNA level. Patients with high AKR1B10 expression had significantly higher disease-free survival than those with low expression within 2 years after liver resection. Multivariate analysis also confirmed high AKR1B10 expression to be a predictor of low risk of early HCC recurrence. In addition, high AKR1B10 expression was found to be a favorable factor of overall survival. These results suggest that AKR1B10 is involved in HBV-related hepatocarcinogenesis, but its high expression could predict low risk of early tumor recurrence in patients with HBV-related HCC after liver resection.

Surgical resection for hepatocellular carcinoma with portal vein tumor thrombus in the Asia-Pacific region beyond the Barcelona Clinic Liver Cancer treatment algorithms: a review and update

Portal vein tumor thrombus (PVTT) usually worsens prognosis of hepatocellular carcinoma (HCC), as characterized by aggressive disease progression, impaired liver function and tolerance to treatment. Conventionally, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) accepted the Barcelona Clinical Liver Cancer (BCLC) treatment algorithms, identifying PVTT as an absolute contra-indication of surgical resection for HCC. HCC-PVTT patients are offered sorafenib as the standard treatment. Evidently, SHARP and Asia-Pacific trials demonstrated that sorafenib only improves overall survival by approximately 3 months in patients with advanced HCC. Besides, BCLC treatment algorithm does not provide different therapeutic recommendations for different degree of PVTT, and only supports single treatment option for each stage of HCC rather than a combination of comprehensive treatments, which limited individual and best care for every HCC-PVTT patients. In the past few years, many surgeons do not restrict surgical resection to HCC with PVTT. There have been new reports demonstrated that surgical treatment is feasible for selected HCC-PVTT patients with resectable tumor and moderate liver function to prolong survival period and elevate life quality as long as PVTT limited to the first-order branch, whereas non-surgical treatments fail to provide comparable therapeutic effects. At present, guidelines on HCC management from mainland China, Japan, and Hong Kong have been updated and a consensus of Asia-Pacific experts has established that portal venous invasion is not an absolute contradiction of surgical resection for HCC. This review summarized the emerging data on surgical resection for HCC-PVTT patients beyond the BCLC treatment algorithms and discussed recent therapeutic conceptualchanges in the Asia-Pacific region.Portal vein tumor thrombus (PVTT) usually worsens prognosis of hepatocellular carcinoma (HCC), as characterized by aggressive disease progression, impaired liver function and tolerance to treatment. Conventionally, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) accepted the Barcelona Clinical Liver Cancer (BCLC) treatment algorithms, identifying PVTT as an absolute contra-indication of surgical resection for HCC. HCC-PVTT patients are offered sorafenib as the standard treatment. Evidently, SHARP and Asia-Pacific trials demonstrated that sorafenib only improves overall survival by approximately 3 months in patients with advanced HCC. Besides, BCLC treatment algorithm does not provide different therapeutic recommendations for different degree of PVTT, and only supports single treatment option for each stage of HCC rather than a combination of comprehensive treatments, which limited individual and best care for every HCC-PVTT patients. In the past few years, many surgeons do not restrict surgical resection to HCC with PVTT. There have been new reports demonstrated that surgical treatment is feasible for selected HCC-PVTT patients with resectable tumor and moderate liver function to prolong survival period and elevate life quality as long as PVTT limited to the first-order branch, whereas non-surgical treatments fail to provide comparable therapeutic effects. At present, guidelines on HCC management from mainland China, Japan, and Hong Kong have been updated and a consensus of Asia-Pacific experts has established that portal venous invasion is not an absolute contradiction of surgical resection for HCC. This review summarized the emerging data on surgical resection for HCC-PVTT patients beyond the BCLC treatment algorithms and discussed recent therapeutic conceptualchanges in the Asia-Pacific region.

Pre‐ and post‐operative HBsAg levels may predict recurrence and survival after curative resection in patients with HBV‐associated hepatocellular carcinoma

To investigate pre‐ and post‐operative levels of HBsAg influence prognosis of patients with hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) after curative resection.

Comprehensive treatments for hepatocellular carcinoma with tumor thrombus in major portal vein.

AIM To evaluate the efficacy of transcatheter arterial chemoembolisation (TACE) compared with surgical intervention and sorafenib for treatment of hepatocellular carcinoma (HCC) in patients with tumor thrombus extending to the main portal vein. METHODS From 2009 to 2013, a total of 418 HCC patients with tumor thrombus extending to the main portal vein were enrolled in this study and divided into four groups. These groups underwent different treatments as follows: TACE (n = 307), surgical intervention (n = 54), sorafenib (n = 15) and palliative treatment (n = 42). Overall survival rates were determined by Kaplan-Meier method, and differences between the groups were identified through log-rank analysis. Coxs proportional hazard model was used to identify the risk factors for survival. RESULTS The mean survival periods for patients in the TACE, surgical intervention, sorafenib and palliative treatment groups were 10.39, 4.13, 5.54 and 2.82 mo, respectively. For the TACE group, the 3-, 6-, 12- and 24-mo survival rates were 94.1%, 85.9%, 51.5% and 0.0%, respectively. The corresponding rates were 60.3%, 22.2%, 0.0% and 0.0% for the surgical intervention group and 50.9%, 29.5%, 0.0% and 0.0% for the sorafenib group. Evidently, the results in the TACE group were significantly higher than those in the other groups (P < 0.0001). Furthermore, no significant difference among survival rates was observed between TACE with/without sorafenib (10.22 mo vs 10.52 mo, P = 0.615). No significant difference in survival rates was also found among the surgical intervention, sorafenib and palliative treatment groups (P > 0.05). These values significantly increased after TACE with/without sorafenib compared with other treatments (P < 0.05). CONCLUSION For HCC patients with tumor thrombus extending to the main portal vein, TACE can yield a higher survival rate than surgical intervention or sorafenib treatment.

Adjuvant transarterial chemoembolization to improve the prognosis of hepatocellular carcinoma following curative resection

The present study aimed to investigate the prognostic factors for recurrence of hepatocellular carcinoma (HCC) following curative resection, and evaluate the efficacy of postoperative adjuvant transarterial chemoembolization (TACE) in improving prognosis. A total of 166 patients who underwent curative resection followed by adjuvant TACE, and 190 patients who underwent curative resection alone were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors of recurrence. Separated based on risk factors, subgroup studies were conducted and the association between TACE and recurrence rates was examined. Postoperative overall survival rates were determined using the Kaplan-Meier method and differences between the two therapeutic strategies were identified through log-rank analysis. Computerized tomography (CT)/magnetic resonance imaging (MRI) images were used to evaluate the function of postoperative adjuvant TACE for enhancing the efficacy of CT/MRI in detecting recurrence. The results of the univariate and multivariate analyses revealed that tumor capsule invasion, vascular invasion, and multiple nodules were risk factors of early recurrence. For patients with these risk factors, recurrence rates were markedly decreased at 6 and 12 months, but not at 18 and 24 months, if TACE was added to curative resection. The hepatitis B virus (HBV) was a risk factor for late recurrence. Postoperative TACE was not effective in reducing the recurrence rate in patients with HBV. Survival increased following curative resection with TACE compared with curative resection alone. Furthermore, adjuvant TACE enhanced the efficacy of CT/MRI in detecting recurrence. Postoperative adjuvant TACE may improve the prognosis of HCC following curative resection.

Negative regulation of MAVS-mediated innate immune response by ASC

Stringent control of the type I interferon signaling pathways is critical to effective host immune responses, however, the molecular mechanisms that negatively regulate these pathways are still poorly understood. Here, we show that apoptosis speck-like protein (ASC), an adaptor protein of inflammasome complex, can inhibit IFN-β signaling response by interacting with mitochondrial antiviral signaling protein (MAVS). Importantly, ASC-specific siRNA knockdown enhanced virus-induced type I interferon production, with consequent reduction of virus replication. Taken together, these results suggest that ASC, as a negative regulator of the MAVS-mediated innate immunity, may play an important role in host protection upon virus infection.

Identification of Candidate Biomarkers in Malignant Ascites from Patients with Hepatocellular Carcinoma by iTRAQ-Based Quantitative Proteomic Analysis

Almost all the patients with hepatocellular carcinoma (HCC) at advanced stage experience pathological changes of chronic liver cirrhosis, which generally leads to moderate ascites. Recognition of novel biomarkers in malignant ascites could be favorable for establishing a diagnosis for the HCC patients with ascites, and even predicting prognosis, such as risk of distant metastasis. To distinguish the proteomic profiles of malignant ascites in HCC patients from those with nonmalignant liver cirrhosis, an iTRAQ pipeline was built up to analyze the differentially distributed proteins in the malignant ascites from HCC patients (n=10) and benign ascites from hepatic decompensation (HD) controls (n=9). In total, 112 differentially distributed proteins were identified, of which 69 proteins were upregulated and 43 proteins were downregulated (ratio <0.667 or >1.3, respectively) in the malignant ascites. Moreover, 19 upregulated proteins (including keratin 1 protein and rheumatoid factor RF-IP20, ratio>1.5) and 8 downregulated proteins (including carbonic anhydrase 1, ratio<0.667) were identified from malignant ascites samples. Functional categories analyses indicated that membrane proteins, ion regulation, and amino acid metabolism are implicated in the formation of HCC malignant ascites. Pathways mapping revealed that glycolysis/gluconeogenesis and complement/coagulation cascades are the mostly affected cell life activities in HCC malignant ascites, suggesting the key factors in these pathways such as Enolase-1 and fibrinogen are potential ascitic fluid based biomarkers for diagnosis and prognosis for HCC.