Study On Ductular Reactions In The Inflammatory Microenvironment And The Association With Prognosis Of Hepatocellular Carcinoma Following Resection

PartⅠStudy on the correlation between peritumoral DR andclinicopathology in hepatocellular carcinomaObjective: To evaluate the peritumoral ductular reaction (DR) in hepatocellularcarcinoma (HCC), and its relationship with the clinicopathological features.Methods: The clinicopathological features and DR were analyzed in106HCCpatients who received curative hepatectomy at the Eastern Hepatobiliary SurgeryHospital from January2001to June2003. Follow-up was completed in December2009. DR was performed by immunohistochemical analysis on peritumoral tissuesections. Relationship between peritumoral DR and clinicopathological features wasperformed by statistical analysis.Results: Increased DR correlated with advanced BCLC stage (p=0.003), TNMstage (p=0.002), with elevated serum ALT (p=0.017), ALP (p=0.007), AFP (p=0.010) and HBsAg (+)(p=4.9E-4). Increased DR was also tended to correlate withmultiple nodules (p=0.004), absence of tumor capsule (p=0.027), severemicroscopic vascular invasion (p=0.031) and early recurrence (p=0.010).Conclusions：Significantly peritumoral DR correlated with aggressive clinico-pathological features. It plays a critical role in the aggressiveness of HCC. PartⅡPeritumoral ductular reaction and survival analysis of hepato-cellular carcinoma after hepatectomyObjective: To appraise the relationship of risk factors with poor overall survivaland recurrence free survival in hepatocellular carcinoma after curative hepatectomy.Methods: The clinicopathological characteristics and DR was analyzed in106HCC patients who received curative hepatectomy at the Eastern HepatobiliarySurgery Hospital from Junuary2001to June2003. The Kaplan–Meier method wasused in overall survival rates and recurrence free survival rates. The Log-Rank testwas used in survival curves. Variables were subjected to multivariate Cox regressionmodeling using forward stepwise variable selection when they with p <0.05inunivariate analysis.Results: The1-,3-,5-,7-year RFS and OS rates were54.7%,24.5%,19.8%,8.5%and71.7%,36.8%,32.1%,20.8%respectively. Both DR and tumor size wereindependent prognostic factors for RFS and OS. DR was associated with elevatedrisks of recurrence (HR=2.380,95%CI=1.250-4.534, p=0.008) and death (HR=4.294,95%CI=2.255-8.177, p=9.3E-06). Tumor size was associated with elevatedrisks of recurrence (HR=1.804,95%CI=1.057-3.080, p=0.031) and death (HR=2.950,95%CI=1.694-5.137, p=1.3E-04). Besides, TNM and necroinflammatorygrade were demonstrated as independent predictors for RFS; while BCLC stage wasindependent prognostic factors for OS.Conclusions：Peritumoral DR is an independent factor which affects overallsurvival and recurrence free survival of HCC. PartⅢStudy on the correlation between peritumoral DR andNecroinflammatory grade, Fibrotic stageObjective: To evaluate association between the peritumoral DR andnecroinflammatory grade, fibrotic stage in the non-tumor liver tissue.Methods: The pathological specimens of liver tissues were obtained from106HCC patients who received curative hepatectomy at the Eastern HepatobiliarySurgery Hospital from January2001to June2003. Peritumoral DR was performed byimmunohistochemical analysis, necroinflammatory grade and fibrotic stage innon-tumor liver sections were scored by H&E. Association between peritumoral DRand necroinflammatory grade, fibrotic stage was performed by statistical analysis.Results: The relationship of peritumoral DR and necroinflammatory grade,fibrotic stage was found significantly. Peritumoral DR significantly correlated withnecroinflammatory grade (r=0.563, p=3.4E-10) and fibrotic stage (r=0.435, p=3.1E-06) in HCC patients.Conclusions： A necroinflammatory microenvironment perhaps promotedperitumoral ductular reactions in HCC. PartⅣStudy on the correlation between peritumoral DR and tumoralEpCAM expressionObjective: To evaluate the peritumoral DR in the non-tumor liver tissue and itsrelationship with expression of tumoral EpCAM in HCC.Methods: The pathological specimens of liver tissues were obtained from106HCC patients who received curative hepatectomy at the Eastern HepatobiliarySurgery Hospital from January2001to June2003. Peritumoral DR and tumoralEpCAM was performed by immunohistochemical analysis on non-tumoral liversections and tumoral tissues. Association between peritumoral DR and tumoralEpCAM expression was performed by statistical analysis.Results: The relationship of peritumoral DR and tumoral EpCAM expressionwas found significantly. Elevated peritumoral DR was closely associated with tumoralEpCAM expression in HCC patients (p=0.016).Conclusions：Elevated peritumoral DR was closely associated with tumoralEpCAM expression in HCC. Peritumoral DR was perhaps associated activation andproliferation of hepatic progenitor cell in HCC.