Yiqun Yan

Perioperative reactivation of hepatitis B virus replication in patients undergoing partial hepatectomy for hepatocellular carcinoma

Background and Aim:  Reactivation of hepatitis B virus (HBV) replication happens in patients who receive transarterial chemoembolization or systemic chemotherapy for hepatocellular carcinoma (HCC). The incidence and risk factors of HBV reactivation during the perioperative period in HCC patients receiving hepatic resection is unknown.

Predictors and clinical outcomes for spontaneous rupture of hepatocellular carcinoma

AIM To determine the risk factors for hepatocellular carcinoma (HCC) rupture, and report the management and long-term survival results of patients with spontaneous rupture of HCC. METHODS Among 4209 patients with HCC who were diagnosed at Eastern Hepatobiliary Surgery Hospital from April 2002 to November 2006, 200 (4.8%) patients with ruptured HCC (case group) were studied retrospectively in term of their clinical characteristics and prognostic factors. The one-stage therapeutic approach to manage ruptured HCC consisted of initial management by conservative treatment, transarterial embolization (TACE) or hepatic resection. Results of various treatments in the case group were evaluated and compared with the control group (202 patients) without ruptured HCC during the same study period. Continuous data were expressed as mean ± SD or median (range) where appropriate and compared using the unpaired t test. Categorical variables were compared using the Chi-square test with Yates correction or the Fisher exact test where appropriate. The overall survival rate in each group was determined using the Kaplan-Meier method and a log-rank test. RESULTS Compared with the control group, more patients in the case group had underlying diseases of hypertension (7.5% vs 3.0%, P =0.041) and liver cirrhosis (87.5% vs 56.4%, P < 0.001), tumor size >5 cm (83.0% vs 57.4%, P < 0.001), tumor protrusion from the liver surface (66.0% vs 44.6%, P < 0.001), vascular thrombus (30.5% vs 8.9%, P < 0.001) and extrahepatic invasion (36.5% vs 12.4%, P < 0.001). On multivariate logistic regression analysis, underlying diseases of hypertension (P = 0.002) and liver cirrhosis (P < 0.001), tumor size > 5 cm (P < 0.001), vascular thrombus (P = 0.002) and extrahepatic invasion (P < 0.001) were predictive for spontaneous rupture of HCC. Among the 200 patients with spontaneous rupture of HCC, 105 patients underwent hepatic resection, 33 received TACE, and 62 were managed with conservative treatment. The median survival time (MST) of all patients with spontaneous rupture of HCC was 6 mo (range, 1-72 mo), and the overall survival at 1, 3 and 5 years were 32.5%, 10% and 4%, respectively. The MST was 12 mo (range, 1-72 mo) in the surgical group, 4 mo (range, 1-30 mo) in the TACE group and 1 mo (range, 1-19 mo) in the conservative group. Ninety-eight patients in the control group underwent hepatic resection, and the MST and median disease-free survival time were 46 mo (range, 6-93 mo) and 23 mo (range, 3-39 mo) respectively, which were much longer than that of patients with spontaneous rupture of HCC undergoing hepatic resection (P < 0.001). The 1-, 3-, and 5-year overall survival rates and the 1-, 3- and 5-year disease-free survival rates in patients with ruptured HCC undergoing hepatectomy were 57.1%, 19.0% and 7.6%, 27.6%, 14.3% and 3.8%, respectively, compared with those of 77.1%, 59.8% and 41.2%, 57.1%, 40.6% and 32.9% in 98 patients without ruptured HCC undergoing hepatectomy (P < 0.001). CONCLUSION Prolonged survival can be achieved in selected patients undergoing one-stage hepatectomy, although the survival results were inferior to those of the patients without ruptured HCC.

Antiviral therapy decreases viral reactivation in patients with hepatitis B virus-related hepatocellular carcinoma undergoing hepatectomy: a randomized controlled trial.

This prospective randomized controlled trial investigated whether antiviral therapy decreases the risk of perioperative viral reactivation in patients with hepatitis B virus–induced hepatocellular carcinoma. Patients with hepatitis B virus–related hepatocellular carcinoma undergoing liver resection were screened. Eighty‐four patients with low viral load were randomly assigned to receive either antiviral treatment with telbivudine or no therapy. The primary outcome was reactivation of viral replication. Secondary outcomes included liver function recovery and postoperative liver insufficiency. A total of 15 patients developed HBV reactivation during the perioperative period, of which 8 (57.1%) were within the first week after hepatectomy. The incidence of viral reactivation during the perioperative period was 2.5% (1/40) in the antiviral‐treated group, compared with 31.8% (14/44) in the control group [HR 0.07 (95%CI 0.01–0.65); P = 0.001]. Liver function recovery was achieved in 82.5% (33/40) patients in the antiviral group on day 30 after hepatectomy, compared with 91.0% (40/44) in the nonantiviral group [HR 1.23 (95%CI 0.98–2.55); P = 0.109]. A total of 7 patients (8.9%) had postoperative liver insufficiency in both groups, but there was no relevant difference between the two groups. Antiviral therapy with telbivudine can significantly decrease the perioperative reactivation of viral replication in patients with hepatitis B virus–related hepatocellular carcinoma undergoing liver resection. Antiviral therapy is an appropriate option for all patients with viral replication undergoing liver resection. (Chinese Clinical Trial Registry, number ChiCTR‐TRC‐0900615).

Double primary hepatic cancer (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) in a single patient: A clinicopathologic study of 35 resected cases

Combined hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) coexisting in the liver have rarely been reported before. The aim of this study is to report on the clinicopathological features and prognosis of patients with double hepatic cancer.

microRNA-23b suppresses epithelial-mesenchymal transition (EMT) and metastasis in hepatocellular carcinoma via targeting Pyk2

Numerous microRNAs (miRNAs) have been shown to play important roles in various cancers, including hepatocellular carcinoma (HCC). However, the functions and mechanisms of the miRNAs involved in HCC progress and metastasis still remain unknown. We downloaded the normalized data of microRNA expression profiling of HCC comparing primary tumor with lung metastasis from GEO database (GSE26323), and gain a group of metastasis-related candidate miRNAs. Among the candidate miRNAs, we focused on miR-23b for further study. The association of metastasis-related miR-23b with survival was also explored. Furthermore, the effects of miR-23b on biological role in HCC were demonstrated by MTT proliferation assay, wound healing and migration assay and the EMT related markers was analyzed by Western blot. Potential target genes of miR-23b were predicted using TargetScan and PicTar and confirmed by luciferase activity assay. A rescue experiment was performed to verify whether the function of miR-23b was exerted via regulation of its target. Our results showed that miR-23b expression was significantly decreased in HCC tissues, which was more importantly, positively correlated to the intrahepatic metastasis of HCC. Meanwhile, patients with low miR-23b expression had significantly poorer prognosis. Overexpression of miR-23b could inhibit MHCC97L cell proliferation, migration, invasion and regulate the expression of MMPs and EMT-associated genes. Moreover, Pyk2, one of the crucial regulators of EMT, was identified as a direct target of miR-23b. In addition, the inhibitory effects of miR-23b overexpression on the metastasis could be restored by Pyk2 overexpression. This study revealed that miR-23b was a tumor suppressor which may regulate HCC migration and invasion by targeting Pyk2 via regulation of EMT, implicating a potential prognostic biomarker and therapeutic target for HCC treatment.

Prognostic factors for survival after hepatic resection of early hepatocellular carcinoma in HBV-related cirrhotic patients

OBJECTIVE The study aimed to identify clinico-pathologic factors that predict survival in early hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV)-related cirrhosis undergoing liver resection. METHODS A population-based cohort was investigated to identify cirrhotic patients with confirmed early HCC (tumor size≤5cm and absence of nodal involvement, metastases, or major vascular invasion) after hepatic resection at the Eastern Hepatobiliary Surgery Hospital (Shanghai, China) from April 2005 and November 2010 using the Surveillance, Epidemiology, and End Results (SEER) database. These patients were studied retrospectively in terms of their clinical characteristics and prognostic factors. Predictors for survival were evaluated using Kaplan-Meier methods and Cox proportional hazards models. Besides, a simple prognostic scoring system was proposed to stratify these patients. RESULTS Of 537 (2.6% of all HCC patients in this period) cirrhotic patients with early HCC identified who had underwent liver resection, 87% were male. Median tumor size was 2.9cm, and 67% of patients had tumors>2cm. Following hepatic resection, overall median and 5-year survival were 75 months and 58%, respectively. Tumor size>2cm (hazard ratio [HR]=1.56), multifocality (HR=1.34), non-anatomic resection (HR=1.44) and vascular invasion (HR=2.03) were associated with worse prognosis (P<0.05). Moreover, these patients could be further stratified into 4 distinct prognostic groups based on the prognostic scoring system developed. CONCLUSION Tumor size>2cm, multifocality, non-anatomic resection and vascular invasion may be used to stratify HBV-related cirrhotic patients with early HCC after resection. Besides, these data also indicate that pathologic staging is important even in small HCC.

Intrahepatic cholangiocarcinoma: a clinicopathologic study of 37 resected cases.

BACKGROUND/AIMS This study aimed to evaluate prognostic factors for intrahepatic cholangiocarcinoma (ICC) patients who underwent surgical procedure. METHODOLOGY A total of 37 ICC patients who underwent curative hepatic resection in our department from November 2006 to June 2009 were recruited in this study. Eighteen clinicopathological factors that might influence survival were selected. Survival rates of patients were calculated using the Kaplan-Meier method and the prognostic factors were selected by the Cox proportional hazard model. RESULTS The overall 1-, 3- and 5- year survival rates were 37.1%, 17.1% and 11.4%, respectively. Univariate analysis showed that tumor thrombus, intrahepatic bile duct dilatation, hepatolithiasis, high serum levels of carbohydrate antigen 19-9 (CA19-9), high serum levels of total bilirubin (TB), low serum levels of prealbumin, high serum levels of γ-glutamyltransferase (γ-GT), high serum levels of alkaline phosphatase (ALP), transfusion, lymph node metastases, advanced UICC stages were significant risk factors for survival. Multivariate analysis identified CA19-9, prealbumin as independent risk factors for postoperative survival. CONCLUSIONS This study suggested serum prealbumin levels could effectively predict the survival of the ICC patients with the treatment of operation. High serum CA19-9 level was associated with poor survival of ICC patients who underwent operation.

Iodine-125 interstitial brachytherapy for experimental liver cancer

Objective:To study the effect of iodine-125 interstitial brachytherapy on liver cancer. Methods: Animal model of human liver cancer was established by injecting SMMC-7721 cells cultivated in vitro subcutaneously into the flank of BALB/c nude mice. Nude mice with tumor of 5 mm in diameter were randomly divided into 2 groups (n = 10). One iodine-125 seed of apparent activity 0. 8 mCi was implanted into the center of tumor in treatment group, whereas an inactive seed was implanted in control group. The other 20 nude mice with tumor reaching 10 mm in diameter were also treated as above. The size of tumor was determined weekly after implantation, and pathological examination and blood routine were taken on the 28th day. Results: Tumor growth was obviously inhibited in treatment group of tumor of 5 mm in diameter, and there was statistically significant difference in tumor volume between treatment and control groups (P0. 01). Around iodine-125 seed, apparent necrosis of tumor was shown in treatment group, accompanied by karyopyknosis and reduced plasma in residual tumor cells microscopically. Tumor growth was not inhibited in either treatment or control group of tumor of 10 mm in diameter. There was no obvious adverse effect except for decreased white blood cells in treatment groups. Conclusion: There is certain effect of iodine-125 interstitial brachytherapy on liver cancer, which is associated with the size of tumor.

Can sorafenib be discontinued in hepatocellular carcinoma patients with a complete response to treatment

Sorafenib is a multi-kinase inhibitor that inhibits angiogenesis by targeting the vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor pathways while blocking cell proliferation by targeting the Ras/mitogen-activated protein kinase signaling pathway. Two global phase III trials [Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP)[1] and Asia-Pacific trial[2]] showed that sorafenib prolonged the survival of patients with advanced hepatocellular carcinoma (HCC). The results of these studies were rapidly disseminated worldwide and were enthusiastically accepted by physicians specializing in liver cancer treatment. Based on the positive results of the SHARP trial,[1] the EU and USA approved sorafenib for advanced HCC in October and November 2007, respectively. Sorafenib was also approved for patients with unresectable and metastatic HCC in July 2008 in China, but patients have to pay the cost by themselves.

Predictive factors for the success of "one-off" ablation in single hepatocellular carcinoma patients who underwent percutaneous radiofrequency ablation

Aim: To investigate the technique’s effectiveness and evaluate the risk factors affecting the success of “one-off” percutaneous ultrasound-guided radiofrequency ablation (RFA) for single hepatocellular carcinoma (HCC). Methods: A total of 462 consecutive patients who received RFA from February 2010 to December 2013 at a single center (Eastern Hepatobiliary Surgery Hospital, Shanghai, China) were enrolled in the study. The patients were followed up for at least 6 months. Herein, this study adopted a new terminology named “one-off” ablation which is defined as achieving complete necrosis and no local residual or recurrent tumor within 6 months after single-session RFA. The incidence of “one-off” RFA was observed and the attributing risk factors were analyzed. A multivariate analysis was conducted to determine the independent predictive factors for the success of “one-off” ablation. Results: The technique’s effectiveness was 90.0% (416/462). After 6 months, 281 patients achieved “one-off” ablation, while 181 patients failed. On univariate analysis, tumor size ≤ 3 cm and tumor further from organs were found to be significantly correlated with “one-off” complete ablation (P = 0.003, and P = 0.010, respectively). On multivariate analysis using a logistic regression, tumor size ≤ 3 cm [odds ratio (OR), 0.534; 95% confidence interval (CI): 0.346-0.825, P = 0.005] and tumor further from organs (OR, 0.593; 95% CI: 0.387-0.909, P = 0.017) remained predictive. Conclusion: Tumor size and tumor location are the predictive factors for the success of “one-off” ablation in patients with single HCC.