Jianjun 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.

Risk factors and surgical outcomes for spontaneous rupture of BCLC stages A and B hepatocellular carcinoma: A case-control study

AIM To investigate the risk factors and surgical outcomes for spontaneous rupture of Barcelona Clinic Liver Cancer (BCLC) stages A and B hepatocellular carcinoma (HCC). METHODS From April 2002 to November 2006, 92 consecutive patients with spontaneous rupture of BCLC stage A or B HCC undergoing hepatic resection were included in a case group. A control arm of 184 cases (1:2 ratio) was chosen by matching the age, sex, BCLC stage and time of admission among the 2904 consecutive patients with non-ruptured HCC undergoing hepatic resection. Histological confirmation of HCC was available for all patients and ruptured HCC was confirmed by focal discontinuity of the tumor with surrounding perihepatic hematoma observed intraoperatively. Patients with microvascular thrombus in the hepatic vein branches were excluded from the study. Clinical data and survival time were collected and analysed. RESULTS Sixteen patients were excluded from the study based on exclusion criteria, of whom 3 were in the case group and 13 in the control group. Compared with the control group, more patients in the case group had underlying diseases of hypertension (10.1% vs 3.5%, P = 0.030) and liver cirrhosis (82.0% vs 57.9%, P < 0.001). Tumors in 67 (75.3%) patients in the case group were located in segments II, III and VI, and the figure in the control group was also 67 (39.7%) (P < 0.001). On multivariate analysis, hypertension (HR = 7.38, 95%CI: 1.91-28.58, P = 0.004), liver cirrhosis (HR = 6.04, 95%CI: 2.83-12.88, P < 0.001) and tumor location in segments II, III and VI (HR = 5.03, 95%CI: 2.70-6.37, P < 0.001) were predictive for spontaneous rupture of HCC. In the case group, the median survival time and median disease-free survival time were 12 mo (range: 1-78 mo) and 4 mo (range: 0-78 mo), respectively. The 1-, 3- and 5-year overall survival rates and disease-free survival rates were 66.3%, 23.4% and 10.1%, and 57.0%, 16.8% and 4.5%, respectively. Only radical resection remained predictive for overall survival (HR = 0.32, 95%CI: 0.08-0.61, P = 0.015) and disease-free survival (HR = 0.12, 95%CI: 0.01-0.73, P = 0.002). CONCLUSION Tumor location, hypertension and liver cirrhosis are associated with spontaneous rupture of HCC. One-stage hepatectomy should be recommended to patients with BCLC stages A and B disease.

Elevated expression of eukaryotic translation initiation factor 3H is associated with proliferation, invasion and tumorigenicity in human hepatocellular carcinoma

Aim We studied the role of eukaryotic translation initiation factor 3 subunit H (EIF3H) in hepatocellular carcinoma (HCC) progression. Results High EIF3H expression was observed in 50.23% patients. Upregulation of EIF3H is an independent predictor for greater rates of cancer recurrence and shorter overall survival in HCC patients. Knockdown of EIF3H expression in HCC cells promoted apoptosis, and inhibited cell growth, colony formation, migration, as well as xenograft growth. TGF-βand MAPK pathways are potentially targeted by EIF3H. Methods EIF3H mRNA expression was measured in HCC tissue samples and paired non-tumor samples (N=60) and results were validated in another dataset of 215 HCC patients. Then EIF3H expression and clinical outcomes were correlated. Malignant phenotypes were studied after EIF3H expression was knocked down with siRNA in HCC cell lines. EIF3H targeted pathways were identified by microarray analysis. Conclusion EIF3H is frequently upregulated and is an independent prognostic marker for HCC patients and EIF3H inhibition mitigates the malignant phenotype. Our data provide novel insight into the function of EIF3H in HCC progression, and suggest that EIF3H may be a potentially valuable biomarker for HCC.

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.

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.

Liver resection for hepatocellular carcinoma: personal experiences in a series of 1330 consecutive cases in China: Liver resection for HCC

Liver resection to treat early stage hepatocellular carcinoma (HCC) is widely practised but surgery for intermediate and advanced stages of HCC is not included in the treatment algorithm of the Barcelona Clinic Liver Cancer, which has been adopted in official guidelines; nevertheless, resection beyond early stages is frequently undertaken and documented.

Pulmonary embolism after transcatheter arterial chemoembolization for hepatocellular carcinoma： a retrospective analysis on 10 years＇ experience

Abstract Objective To study the clinical characteristics and treatment of pulmonary embolism (PE) after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Methods The clinical records of 13 512 patients diagnosed with HCC and received TACE from January 2000 to December 2009 were reviewed. Among these patients, 5 031 were allocated into group A who had one or more disorders like diabetes, hypertension, coronary heart disease, obesity or varicose vein of lower limb, while the other 8 481 patients who did not have such disorders were in group B. Results A total of 39 185 TACE procedures were performed for the 13 512 patients. Five (0.01%) patients in group A developed PE after TACE, of whom two recovered 4 and 5 d later with early anticoagulant therapy while the hypertension, coronary heart disease, obesity or varicose vein of lower limb are possibly more likely to develop PE other 3 died of respiratory failure within 5 h. The mortality of PE was 60% (3/5). Conclusion: HCC patients with diabetes, after TACE than those without such disorders. Patients who have such disorders should be more carefully observed after TACE and early treatment with heparin should be applied once PE develops.