Wen-Chao Zhao

Postoperative adjuvant transcatheter arterial chemoembolisation improves survival of intrahepatic cholangiocarcinoma patients with poor prognostic factors: Results of a large monocentric series

BACKGROUND The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is currently unsatisfactory. The aims of this study were to identify prognostic factors after curative ICC resection, and to evaluate the effects of postoperative transcatheter arterial chemoembolisation (TACE). METHODS A retrospective analysis was conducted of 114 ICC patients who underwent curative resection from January 2005 to December 2006. Relationships between survival and clinicopathological factors were evaluated using univariate and multivariate analyses. The benefits of adjuvant TACE were investigated separately. RESULTS The cumulative 1-, 3-, and 5-year survival rates were 63%, 26%, and 15%, respectively. Multivariate analysis revealed that tumour size ≥ 5 cm (hazard ratio [HR] 1.875, 95% CI 1.139-3.088, P=0.013) and advanced TNM stage (stage III or IV) (HR 1.681, 95% CI 1.035-2.732, P=0.036) were independently associated with poor prognosis. Fifty-seven patients underwent adjuvant TACE. In patients with poor prognostic factors, TACE improved the survival rate (P<0.001). However, in patients without poor prognostic factors, TACE did not significantly change the survival rate (P=0.724). CONCLUSIONS Postoperative adjuvant TACE can prolong survival in ICC patients with tumour size ≥ 5 cm or advanced TNM stage.

Preoperative predictors of short-term survival after hepatectomy for multinodular hepatocellular carcinoma

AIM To investigate preoperative factors associated with poor short-term outcome after resection for multinodular hepatocellular carcinoma (HCC) and to assess the contraindication of patients for surgery. METHODS We retrospectively analyzed 162 multinodular HCC patients with Child-Pugh A liver function who underwent surgical resection. The prognostic significance of preoperative factors was investigated by univariate analysis using the log-rank test and by multivariate analysis using the Cox proportional hazards model. Each independent risk factor was then assigned points to construct a scoring model to evaluate the indication for surgical intervention. A receiver operating characteristics (ROC) curve was constructed to assess the predictive ability of this system. RESULTS The median overall survival was 38.3 mo (range: 3-80 mo), while the median disease-free survival was 18.6 mo (range: 1-79 mo). The 1-year mortality was 14%. Independent prognostic risk factors of 1-year death included prealbumin < 170 mg/L [hazard ratio (HR): 5.531, P < 0.001], alkaline phosphatase > 129 U/L (HR: 3.252, P = 0.005), α fetoprotein > 20 μg/L (HR: 7.477, P = 0.011), total tumor size > 8 cm (HR: 10.543; P < 0.001), platelet count < 100 × 10⁹/L (HR: 9.937, P < 0.001), and γ-glutamyl transpeptidase > 64 U/L (HR: 3.791, P < 0.001). The scoring model had a strong ability to predict 1-year survival (area under ROC: 0.925, P < 0.001). Patients with a score ≥ 5 had significantly poorer short-term outcome than those with a score < 5 (1-year mortality: 62% vs 5%, P < 0.001; 1-year recurrence rate: 86% vs 33%, P < 0.001). Patients with score ≥ 5 had greater possibility of microvascular invasion (P < 0.001), poor tumor differentiation (P = 0.003), liver cirrhosis with small nodules (P < 0.001), and intraoperative blood transfusion (P = 0.010). CONCLUSION A composite preoperative scoring model can be used as an indication of prognosis of HCC patients after surgical resection. Resection should be considered with caution in patients with a score ≥ 5, which indicates a contraindication for surgery.

Dexamethasone decreases hepatocellular carcinoma cell sensitivity to cisplatin-induced apoptosis.

BACKGROUND/AIMS Despite the fact that dexamethasone (DEX), a synthesized glucocorticoid (GCs), in vitro has pro-apoptotic effects on lymphoid cells, it has been suggested to induce apoptosis resistance toward chemotherapy in lung, cervical and breast cancer cell lines. However, the mechanisms by which GCs inhibit apoptosis in some cells have not been elucidated. The aim of this study is to investigate the effect of DEX on cisplatin (CIS)-induced hepatocellular carcinoma cell proliferation, apoptosis and to determine apoptosis-related gene expression on mRNA and protein levels. METHODOLOGY MTT assay, annexin V-FITC as well as Hoechst33258 staining were performed to detect hepatocellular carcinoma cell proliferation and apoptosis, respectively. RT-PCR and western blot were used to determine Bcl-2 and Bcl-xL expression. RESULTS DEX alone did not cause any obvious change to HepG2 and SNU449 cell proliferation. When pretreated with DEX followed by CIS treatment, cells showed resistance to CIS-induced cytotoxicity by MTT assay and apoptosis detected by Annexin V-FITC kit double staining. Hoechst33258 staining showed that CIS caused cell nuclear condensation, a sign of apoptosis and DEX pretreatment reduced the proportion of apoptotic cells. Anti-apoptotic genes Bcl-2 and Bcl-xL expression levels decreased after CIS treatment, but increased again after DEX addition. CONCLUSIONS DEX can decrease hepatocellular carcinoma cell sensitivity to CIS-induced cell death by preventing cell apoptosis.

Alpha-fetoprotein: the predictor of microvascular invasion in solitary small hepatocellular carcinoma and criterion for anatomic or non-anatomic hepatic resection.

BACKGROUND/AIMS This study aimed to identify the preoperative predictors of microvascular invasion (MVI) in solitary small hepatocellular carcinoma (HCC) and evaluate their application in surgical treatment. METHODOLOGY We retrospectively analyzed 161 patients with solitary small HCC who underwent curative hepatic resection. Overall and disease-free survival rates were calculated by Kaplan-Meier method and compared by log-rank test. The independent predictors were identified by Cox proportional hazards model. RESULTS MVI was an independent predictor of both overall and disease-free survival. In 51 patients with MVI, anatomic resection achieved better survival than non-anatomic resection. However, anatomic resection and non-anatomic resection brought similar survival in patients without MVI. Alpha-fetoprotein (AFP) was identified as the unique predictor of MVI (HR=2.773, p=0.004). Anatomic resection achieved better survival outcome than non-anatomic resection when AFP >100μg/L (5-year overall survival rate: 85% vs. 55%, p=0.024; 5-year disease-free survival rate: 37% vs. 21%, p=0.025), while there was no statistical survival difference between anatomic and non-anatomic resection when AFP <=100μg/L (5-year overall survival rate: 85% vs. 76%, p=0.838; 5-year disease-free survival rate: 48% vs. 49%, p=0.921). CONCLUSIONS Compared with non-anatomic resection, anatomic hepatic resection improves overall and disease-free survival of solitary small HCC patients with AFP >100μg/L.

Porcine Partial Liver Transplantation Without Veno-venous Bypass: An Effective Model for Small-for-Size Liver Graft Injury

OBJECTIVE Partial liver transplantation is currently gaining wider acceptance, which alleviates donor organ shortage, but also reveals the problem of small-for-size (SFS) syndrome. The precise mechanism behind it remains unknown. Large animal models for SFS syndrome are being developed using veno-venous bypass (VVB), however, splenectomies have often become necessary making the models useless for clinical situations. This study establishes a clinically well-simulated and effective model of SFS graft injury without VVB. METHODS In this study, 30% and 100% of liver grafts were orthotopically transplanted to pigs in groups A (n = 12) and B (n = 5), respectively, both without VVB. Intraoperative hemodynamics and metabolic parameters were assessed consecutively. The operative survival rates were evaluated during 7 days of follow-up as well as the serum biochemical profiles, the kinesis of portal pressure gradient, and the pathological findings. RESULTS All the recipients survived the anhepatic period except one in group A who died of irretrievable acidosis. The tolerance rate for non-VVB were 91.7% (11/12) in group A and 100% (5/5) in group B with no significant differences. The 7-day survival rate in group A was significantly less than that for group B (50% versus 100%, P < .05) with more prolonged prothrombin times, increased bilirubin and alanine aminotransferase levels, and persistantly higher values of portal pressure gradient during almost the entire follow-up period. Accordingly, the pathological findings clarified more severe microvascular impairments in group A than group B. CONCLUSION These data suggest that the model of pigs transplanting with 30% liver grafts without VVB is safe and reproducible. The good clinical simulation on operative procedures and clinicopathological performance indicates it is a more rational model for further research on SFS syndrome.