Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution's experience with 398 consecutive patients

BACKGROUND: Surgical resection is an important curative treatment for hepatocellular carcinoma (HCC); however, some patients experience an unexpected recurrence even after hepatectomy. The present study aimed to investigate risk factors and predictive criteria for early and late recurrence of HCC after resection.METHODS: A retrospective analysis of 398 Chinese patients who received curative resection for HCC was conducted. Patients were divided into three groups: without recurrence, early recurrence and late recurrence. Prognostic factors and predictive criteria for early and late recurrence were statistically analyzed. RESULTS: The cumulative recurrence-free survival rates at1, 2, 3, 4, and 5 years were 75.5%, 58.2%, 54.1%, 40.5%, and28.7%, respectively. The distribution of the time to recurrence suggested that recurrence could be divided into early phase(before 2 years; n=164) and late phase (after 2 years; n=83)Cox’s multivariate proportional hazard model analysis revealed that multiplicity of tumors (P=0.004) and venous infiltration(P=0.002) were independent risk factors associated with early recurrence. In contrast, indocyanine green retention rate at 15minutes (P=0.007), serum albumin level (P=0.045), and HBeAg status ( =0.028) proved to be significant independent adverse prognostic factors for late recurrence. Patients with at least 1of the 2 early recurrence risk factors (multiplicity of tumors ≥2and venous infiltration) or with 2 or more late recurrence risk factors are often susceptible to recurrence (P=1.36e-4 and 1.0e-6respectively).CONCLUSIONS: Early and late recurrences correlate with different risk factors and predictive criteria. Early recurrence primarily results from intrahepatic metastases, while late recurrence may be multicentric in origin.

An accurate predictor of liver failure and death after hepatectomy:A single institution's experience with 478 consecutive cases

AIM:To establish a reliable definition of postoperative liver failure(PLF)and allow the prediction of outcomes after hepatectomy.METHODS:The clinical data of 478 consecutive patients who underwent hepatectomy were retrospectively analyzed.The examined prognostic factors included the ratio of total bilirubin(TBIL)on postoperative day(POD)X to TBIL on POD 1(TBIL-r1)and the ratio of the international normalized ratio(INR)on POD X to the INR on POD 1(INR-r1)for PODs 3,5 and 7.Student’s t test,theχ2test,logistic regression,survival analysis and receiver operating curve analysis were used to evaluate risk factors and establish the definition of postoperative liver failure(PLF).RESULTS:Fourteen patients(2.9%)died of liver failure within 3 mo of surgery.Significant differences were found between patients who died of liver failure and the remaining patients in terms of TBIL-r1 and INR-r1on PODs 3,5 and 7.The combination of TBIL-r1 and INR-r1 on POD 5 showed strong predictive power for liver failure-related death(sensitivity 92.9%and specificity 90.1%).The hepatic damage score(HDs),which was derived from TBIL-r1 and INR-r1,was used to define the degree of metabolic functional impairment after resection as mild(HDs=0),reversible hepatic"dysfunction"(HDs=1)or fatal hepatic failure(HDs=2).Furthermore,the indocyanine green retention rate at 15 min(ICG-R15)and the number of resected segments(RSs)were identified as independent predictors of the HDs.A linear relationship was found between ICG-R15 and RSs in the HDs=2 group.The regression equation was:RSs=-0.168×ICG-R15+5.625(r2=0.613,F=14.257,P=0.004).CONCLUSION:PLF can be defined by the HDs,which accurately predicts liver failure-related death after liver resection.Furthermore,the ICG-R15 and RSs can be used as selection criteria for hepatectomy.

Mesohepatectomy versus extended hemihepatectomy for centrally located hepatocellular carcinoma

BACKGROUND: Extended hemihepatectomy is usually recommended to treat large centrally located hepatocellular carcinoma (HCC). However, the morbidity and mortality are high because of the postoperative liver failure. Mesohepatectomy is seldom used because of its technical complexity This study aimed to evaluate the short-term and long-term curative effect of mesohepatectomy. METHODS: From January 2002 to September 2008, a total of 198 consecutive patients with centrally located HCC underwent hepatectomy in our department. According to the surgical procedures, they were divided into mesohepatectomy (group M, n=118), extended right hemihepatectomy (group RE, n=47) and extended left hemihepatectomy (group LE, n=33) groups. The surgical techniques, clinical pathological characteristics and outcomes were compared between group M, group RE and group LE. RESULTS: The operative time of group M was significantly longer than that of the other two groups (P<0.05); however the total bilirubin on postoperative day 3 in group M was the lowest among the three groups (P<0.01). In group M, the number of the patients whose resection margin achieving 1 cm was significantly lower than that of the other two groups (P<0.05). The mortality rates in groups M, RE and LE were 2.5%, 8.5% and 3.0%, respectively (P>0.05). The morbidity rate in group M was significantly lower than that in group RE (37.3% vs 55.3%, P=0.034), but not in group LE (37.3% vs 24.2%, P=0.163). The biliary leakage tended to be more common in group M (10.2%, P>0.05). The incidence of postoperative liver failure in group M was significantly lower than that in group RE (1.7% vs 10.6%, P=0.032), but not in group LE (1.7% vs 6.1%, P=0.208). The 1-, 3- and 5-year tumor-free survival rates and the overall survival rates after mesohepatectomy were 53.4%, 30.5% and 16.9% and 67.8%, 45.5% and 28.9%, respectively. CONCLUSIONS: Mesohepatectomy is a safe and effective technique for centrally located HCC patients. Compared with extended right hemihepatectomy, mesohepatectomy can retain residual liver volume to the maximum limit and reduce postoperative liver failure rate. But no significant advantage was found compared mesohepatectomy to extended left hemihepatectomy.

MicroRNAs involved in drug resistance of breast cancer by regulating autophagy

Autophagy is a conserved catabolic process characterized by degradation and recycling of cytosolic components or organelles through a lysosome-dependent pathway.It has a complex and close relationship to drug resistance in breast cancer.MicroRNAs(miRNAs)are small noncoding molecules that can influence numerous cellular processes including autophagy,through the posttranscriptional regulation of gene expression.Autophagy is regulated by many proteins and pathways,some of which in turn have been found to be regulated by miRNAs.These mi RNAs may affect the drug resistance of breast cancer.Drug resistance is the main cause of distant recurrence,metastasis and death in breast cancer patients.In this review,we summarize the causative relationship between autophagy and drug resistance of breast cancer.The roles of autophagy-related proteins and pathways and their associated miRNAs in drug resistance of breast cancer are also discussed.