Expression and clinical significance of TAp73α, p53, PCNA and apoptosis in hepatocellular carcinoma

AIM: To study the prognostic role of TAp73α, p53,proliferating cell nuclear antigen (PCNA) and apoptosis in patients with hepatocellular carcinoma (HCC) after surgical tumor ablation.METHODS: Forty-seven human resected HCC tissues and 42 adjacent non-cancerous tissues were studied with 10 normal liver tissues as control group. TAp73α, p53, and PCNA were detected with Elivision immunohistochemistry.Terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP-biotin nick-end labeling (TUNEL) method was used to detect the apoptosis cells. All clinical and pathological materials were analyzed by SPSS10.0statistical package.RESULTS: TAp73α overexpressed in HCC tissues (36.2%)when compared with adjacent non-cancerous tissues(2.38%, P<0.005) and normal liver tissues (0, P<0.01).Mutant type p53 (rot-p53) overexpressed in HCC tissues(38.3%) when contracted with adjacent non-cancerous tissues (16.7%, P<0.05) and normal liver tissues (0,P<0.01). Proliferation index (PI) level in HCC tissues was significantly higher than that in adjacent non-cancerous tissues (30.34%±4.46% vs27.88%±5.89%, t, P= 0.028).Apoptosis index (AI) level in HCC tissues was higher than that in adjacent non-cancerous tissues (8.62%±2.28%vs7.38%±2.61%, t, P = 0.019). Expression of TAp73α was associated with lymph node metastasis and rot-p53,with r = 0.407 and 0.265, respectively. Expression of rot-p53 was associated with Edmondson‘s stage and AFP,with r = 0.295 and -0.357, respectively. In Kaplan-Meier univariant analysis, TAp73α, AFP, TNM stage, portal vein invasion, liver membrane invasion and HBsAg correlated with prognosis (log rank, P= 0.039, 0.012, 0.002, 0.000,0.014, 0.007, respectively). Multivariant Cox regression analysis showed that TAp73α, AFP, TNM stage, portalve in invasion, liver membrane invasion and age were independent factors of prognosis.CONCLUSION: These results suggest that TAp73α can be used as a prognostic indicator of patients with HCC undergoing surgical tumor ablation. AFP, TNM, portal vein invasion, liver membrane invasion and age also have a potency of predicting the prognosis of HCC.     

Long-term outcomes after hepatectomy of huge hepatocellular carcinoma: A single-center experience in China

Background: Currently, hepatectomy remains the first-line therapy for hepatocellular carcinoma(HCC). However, surgery for patients with huge( 10 cm) HCCs is controversial. This retrospective study aimed to explore long-term survival after hepatectomy for patients with huge HCC. Methods: The records of 188 patients with pathologically confirmed HCC who underwent curative hepatectomy between 2007 and 2017 were reviewed; patients were divided into three groups according to tumor size: huge( 10 cm; n = 84), large(5–10 cm; n = 51) and small( 5 cm; n = 53) HCC. Kaplan-Meier analysis was used to assess overall survival(OS) and disease-free survival(DFS), and log-rank analysis was performed for pairwise comparisons among the three groups. Risk factors for survival and recurrence were analyzed using the Cox proportional hazard model. Results: The median follow-up period was 20 months. Although the prognosis of small HCC was better than that of huge and large HCC, OS and DFS were not significantly different between huge and large HCC( P = 0.099 and P = 0.831, respectively). A family history of HCC, poor Child-Pugh class, vascular invasion, diolame, pathologically positive margins, and operative time ≥240 min were identified as independent risk factors for OS and DFS in a multivariate model. Tumor size( 10 cm) had significant effect on OS, and postoperative antiviral therapy and postoperative complications also had significant effects on DFS. Conclusions: Huge HCC is not a contraindication of hepatectomy. Although most of these patients experienced recurrence after surgery, OS and DFS were not significantly different from those of patients with large HCC after resection.     

Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score

AIM: The survival time of patients with hepatocellular carcinoma (HCC) after resection is hard to predict. Both residual liver function and tumor extension factors should be considered. A new scoring system has recently been proposed by the Cancer of the Liver Italian Program (CLIP).CUP score was confirmed to be one of the best ways to stage patients with HCC. To our knowledge, however, the literature concerning the correlation between CLIP score and prognosis for patients with HCC after resection was not pubhshed. The aim of this study is to evaluate the recurrence and prognostic value of CLIP score for the patients with HCC after resection.METHODS: A retrospective survey was carried out in 174patients undergoing resection of HCC from January 1986 toJune 1998. Six patients who died in the hospital afteroperation and 11 patients with the recurrence of the diseasewere excluded at 1 month after hepatectomy. By the end ofJune 2001, 4 patients were lost and 153 patients with curativeresection have been followed up for at least three years.Among 153 patients, 115 developed intrahepatic recurrenceand 10 developed extrahepatic recurrence, whereas the other28 remained free of recurrence. Recurrences were classifiedinto early ( ＜ / = 3 year) and late ( ＞ 3 year) recurrence. TheCLIP score included the parameters involved in the Child-Pugh stage (0-2), plus macroscopic tumor morphology (0-2), AFP levels (0-1), and the presence or absence of portalthrombosis (0-1)o By contrast, portal vein thrombosis wasdefined as the presence of tumor emboli within vascularchannel analyzed by microscopic examination in this study.Risk factors for recurrence and prognostic factors forsurvival in each group were analyzed by the chi-square test,the Kaplan-Meier estimation and the COX proportionalhazards model respectively.RESULTS: The 1-, 3-, 5-, 7-, andl0-year disease-free survivalrates after curative resection of HCC were 57.2 %、 28.3 %、23.5 %、 18.8 % and 17.8 %, respectively. Median survivaltime was 28,16,10,4,and 5 mo for CLIP score 0,1,2,3, and 4to 5, respectively. Early and late recurrence developed in109 patients and 16 patients respectively. By the chi-squaretest, tumor size, micrusatsllite, venous invasion, tumortype (uninodular, muitinodular, massive), tumor extension( ＜ / = or ＞ 50 % of liver parenchyna replaced by tumor),TNM stage,CLIP score,and resection margin were the risk factors for early recurrence,whereas CLIP score and Child-Pugh stage were significant risk factors for late recurrence. in univariate survival analysis,Child-Pugh stages,resection margin,tumor size,microsatellite,venous invasion,tumor type,tumor extension,TNM stages,and CLIP score were associated with prognosis.The multivariale analysis by COX proportional hazards modes showed that the independent predictive factors of survival were resection margins and TNM stages. CONCLUSION:CLIP score has displayed a unique superiority in predictin the tumor early and late recurrence and prognosis in the patients with HCC after resection.     

Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma

AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 ± 10.1), 31 cirrhosis patients(mean age of59.3 ± 6.3) and 33 healthy volunteers(mean age of51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein(AFP) values with HCC clinicopathological features, such as tumor size,number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion(diameters; ≤ 3 cm, 3-5 cmand ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer(BCLC)criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alphafetoprotein levels were kept at-80 ℃ until use.Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.RESULTS: In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number,presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls(P 0.001). Prolidase levels were significantly associated with tumor size and number(P 0.001, P = 0.002,respectively). Prolidase levels also differed in patients in terms of BCLC staging classification(P 0.001).Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis(P 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately(P = 0.032,P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation(r = 0.616; P 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification,whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.     

Role of blood AFP mRNA and tumor grade in the preoperative prognostic evaluation of patients with hepatoceiluiar carcinoma

AIM: To explore the potential prognostic role of preoperative tumor grade and blood AFP mRNA in a cohort of patients with hepatocellular carcinoma (HCC) eligible for radical therapies according to a well-defined treatment algorithm not including nodule size and number as absolute selection criteria. METHODS: Fifty patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (1) histological assessment of tumor grade by means of percutaneous biopsies; (2) determination of AFP mRNA status in the blood; (3) patient's eligibility for radical therapies. RESULTS: At preoperative evaluation, 54% of the study group had a well-differentiated HCC, 42% had AFP mRNA in the blood, 40% had a tumor larger than 5 cm and 56% had more than one nodule. Surgery (resection or liver transplantation) was performed in 29 patients, while 21 had percutaneous ablation procedures. After a median follow-up of 28 mo, 12-, 24-, and 36-mo survival rates were 78%, 58%, and 51%, respectively. Surgical therapy, performance status and three tumor-related variables (AFP mRNA, HCC grade and gross vascular invasion) resulted as significant survival predictors at univariate analysis. Nodule size and number did not perform as significant prognosticators. Multivariate study selected only surgical therapy and a biologically early HCC profile (AFP mRNA negative and well-differentiated tumor without gross vascular invasion) as independent survival variables. CONCLUSION: The preoperative determination of tumor grade and blood AFP mRNA status may potentially refine the prognostic evaluation of HCC patients and improve the selection process for radical therapies.     

Relationship between the expression of iNOS,VEGF,tumor angiogenesis and gastric cancer

AIM：To in vestigate the relationship between the expression of inducible nitric oxide synthase(iNOS),vascular endothelial growth factor(VEGF),the microvascular density(MVD)and the pathological features and clinical staging of gastric cancer.METHODS:Immunohistochemical staining was used for detecting the expression of iNOS and VEGFin46resected specimens of gastric carcinoma;the monoclonal antibody against CD34 was used for displaying vascular endothelial cells,and MVD was detected by counting of CD34-positive vascular endothelial cells.RESULTS:Of 46resected specimens of gastric carcinoma,the rates of expressions of iNOS and VEGF were 58.70%and76.09%,respectively,and MVDaveraged55.59±19.39,Judged by the standard TNM criteria,the rate of expression of iNOS in stageⅣ（84.46%)was higher than those in stageⅠ,Ⅱ,Ⅲ（Fish exact probabilities test,P=0.019,0.023and 0.033,respectively);the rates of expression of VEGFin stage Ⅲ,Ⅳ（76.0%,92.31%,respectively)were higher than those in stageⅠ,Ⅱ（Fis exact probabilities test,P=0.031,0.017,0.022and0.019).MVDs in stageⅢ,Ⅳ（64.72±14.96,67.09±18.29,respectively)were higher than those in stageⅠ,Ⅱ(t\2.378,4.015,2.503and2.450,P<0.05,P<0.001,P<0.001,P<0.05,respectively),In37gastric carcinoma specimens with lymph node metastasis,MVD(68.69±18.07)and the rates of expression of iNOS and VEGF(70.27%,83.78%,respectively)were higher than those in the specimens with absence of metastasis(t=2.205,X^2=6.3587,X^2=6.2584,P<0.01,P<0.05,P<0.05,respectively),MVD and the expressions of iNOS and EGF were not correlated to the location,size or grade of tumor,nor with the depth of invasion of tumor;MVDs in the positive iNOS and VEGF specimens(59.88±18.02,58.39±17.73,repectively)were higher than those in the negative iNOS and VEGF specimens(X^2=6.3587and 6.1574,P<0.05,P<0.05,respectively);thus the expressions of iNOS and VEGF was correlated to MVD,but the expression of iNOS was not correlated to that of VEGF,In addition.of the 46 surviving patients,the 5-year survival rate of patients with positive iNOS or VEGF tumors was significantly less than that of patients with negative iNOS-or VEGF tumors(X^2=4.3842and 5.4073,P<0.05,P<0.05.respectively).CONCLUSION:The expressions of iNOS and VEGF are colosely related to tumor angiogenesis,and are involved in the advancement and the lymph node metastasis;thusMVD and the expressions of iNOS and EGF may serve indexes for evaluating staging of gastric carcinoma and forecasting its risk of metastasis,which will help establish a comprehensive therapeutical measure of post-operative patients and provide a new approach to tumor therapy.     

Postoperative adjuvant arterial chemoembolization improves survival of hepatocellular carcinoma patients with risk factors for residual tumor： A retrospective control study

AIM: To evaluate the effect of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on the prognosis of hepatocellular carcinoma (HCC) patients with or without risk factors for the residual tumor. METHODS: From January 1995 to December 1998, 549 consecutive HCC patients undergoing surgical resection were included in this research. There were 185 patients who underwent surgical resection with adjuvant TACE and 364 patients who underwent surgical resection only. Tumors with a diameter more than 5 cm, multiple nodules, and vascular invasion were defined as risk factors for residual tumor and used for patient stratification. Kaplan-Meier method was used to analyze survival curve and Cox proportional hazard model was used to evaluate the prognostic significance of adjuvant TACE.RESULTS: In the patients without any risk factors for the residual tumor, the 1-, 3-, 5-year survival rates were 93.48%,75.85%, 62.39% in the control group and 97.39%, 70.37%,50.85% in the adjuvant TACE group, respectively. There was no significant difference in the survival between two groups (P = 0.3956). However, in the patients with risk factors for residual tumor, postoperative adjuvant TACE significantly prolonged the patients‘ survival. There was a statistically significant difference in survival between two groups (P= 0.0216). The 1-, 3-, 5-year survival rates were 69.95%, 49.86%, 37.40% in the control group and 89.67%,61.28%, 44.36% in the adjuvant TACE group, respectively. Cox proportional hazard model showed that tumor diameter and cirrhosis, but not the adjuvant TACE, were the significantly independent prognostic factors in the patients without risk factors for residual tumor. However, in the patients with risk factors for residual tumor adjuvant TACE, and also tumor diameter, AFP level, vascular invasion, were the significantly independent factors associated with the decreasing risk for patients‘ death from HCC. CONCLUSION: Postoperative adjuvant TACE can prolong the survival of patients with risk factors for residual tumor,but can not prolong the survival of patients without risk factors for residual tumor.     

Multivariate statistical analysis of clinicopathologic factors influencing survival of patients with bile duct carcinoma

AIM：To evaluate the influence of various clinicopathologic factors on survival of patients with bile duct carcinoma after cuative resection.METHODS:A retrospective analysis was made for 86cases of bile duct carcinoma treated from January 1981to September1995,Fifteen clinicopathologic factors possibly influencing survival were selected.Independent variables were first analyzed by univariate methods.Survival for variable was estimated by the method of Kaplan and Meier.The variables that were statistically significant by univariate analysis were included in a multivariate analysis,which were confirmed using the Cox stepwise proportion hazard model with the help of SPSS10.0for Windows software.RESULTS:The overall cumulative survival rate was72.6%at 1year,32.4%at3years,and18.7%at5years,The results of univariate analysis showed that the major significant prognostic factors influencing survival of these patients were histological type of lesion.lymap node metastasis,pancreatic invasion.duodenal invasion,perineural invasion,macroscopic vessel involvement,resected surgical margin and depth of cancer invasion(P=0.02,0.02,0.004,0.005,0.01,0.43,0.03and0.04).Age,sex,location of tumor,size of tumor,macroscopic type of lesions,hepatic metastasis,and hepatic invasion were n ot significantly associated with prognosis(P>0.05).Pancreatic invasion.perineural invasion and lymph node metastases were the three most imprtant prognostic factors by multivariate analysis using the Cox proortional hazards model.CONCLUSION;Pancreatic invasion.perineural invasion and lymph node metastases are the most important prognostic factors for bile duct carcinoma after curative resection.     

Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To analyze hepatocellular carcinoma(HCC) patients with portal vein tumor thrombosis(PVTT) using the tumor-node-metastasis(TNM) staging system.METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009.We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system(7th edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center.Portal vein invasion(vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein,vp2 as an invasion or tumor thrombus in the second branch of the portal vein,vp3 as an invasion or tumor thrombus in the first branch of the portal vein,and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side.RESULTS: The cumulative 5-year overall survival(5yr OS) and 5-year disease-free survival(5yr DFS) rates of the 372 patients were 58.3% and 31.3%,respectively.The 5yr DFS and 5yr OS of vp3-4 patients(n = 10) were 20.0%,and 30.0%,respectively,which was comparable with the corresponding survival rates of vp1-2 patients(P = 0.466 and 0.586,respectively).In the subgroup analysis of patients with macroscopic PVTT(vp2-4),the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not(P = 0.747).There was a significant difference in the DFS between patients with stage Ⅰ HCC and those with stage Ⅱ HCC(5yr DFS 39.2% vs 23.1%,P 0.001); however,theDFS for stage Ⅱ was similar to that for stage Ⅲ(5yrD FS 23.1% vs 13.8%,P = 0.330).In the subgroup analysis of stage Ⅱ-Ⅲ HCC(n = 148),only alpha-fetoprotein(AFP) 100 mg/dL was independently associated with DFS.CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2.AFP stratified the stage Ⅱ-Ⅲ HCC patients according to prognosis.     

Transcatheter arterial embolization treatment in patients with hepatocellular carcinoma and risk of pulmonary metastasis

AIM: To investigate the relationship between transcatheter arterial embolization (TAE) and pulmonary metastasis in subjects with hepatocellular cardnoma (HCC).METHODS: A total of 287 patients with HCC followed up for more than i week were included. 102 patients underwent transcatheter arterial embolization (TAE group) and 185 received conservative treatment (control group). Thepatients′ chest x-rays and chest CT scans were examined for pulmonary metastasis.RESULTS: Patients with TAE had a median survival of 19.3 months while that of the control group was only 10.0 months(P<0.05). Pulmonary metastasis occurred in 14 (13.7 %) patients in the TAE group and 14 (7.6 %) patients in the control group, there was no significant difference (P>O.05).The l-year, 2-year and 5-year cumulative incidence of pulmonary metastasis was 11.8 %, 17.6 % and 24.0 % in the TAE group and 7.0 %, 13.0 % and 21.7 % in the control group, respectively (P>0.O5). On the univariate analysis,tumor size, abnormal serum alanine aminotransferase levels and heterogeneity on sonography were significantly associated with pulmonary metastasis. However, on the multivariate analysis, only tumor size was significantly predictive of pulmonary metastasis.CONCLUSION: TAE is effective on prolonging survival of patients with HCC. It does not significantly increase the risk of pulmonary metastasis. Tumor size is the only significant predictive factor associated with lung metastasis.     

Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion

AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer(BCLC) early(A) and intermediate(B) stage hepatocellular carcinoma(HCC) patients with microvascular invasion(MVI).METHODS A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival(RFS) and overall survival(OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE. RESULTS Univariate and multivariate analyses demonstrated that serum AFP level 400 ng/m L, tumor size 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size 5 cm, HBV-DNA copies 1 x 104 IU/m L, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level 400 ng/m L, tumor size 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE.CONCLUSION PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early-and intermediate-stage HCC patients with MVI.     

High expression of TRAF4 in hepatocelullar carcinoma as an independent negative survival and recurrence predictor

Objective: To identify potential tumor markers for the development and recurrence of hepatocelullar carcinoma(HCC), this research studied the relationship between the expression of the tumor necrosis factor receptor-associated factor 4(TRAF4) and tumor angiogenesis together with its survival time of HCC patients. Methods: The expressions of TRAF4,vascular endothelial growth factor and CD34 were performed upon 90 patients with curative liver resection between August 2006 and November 2009 by immunohistochemical method in locally advanced HCC and adjacent non-tumoral liver. The expression of TRAF4 was determined by the Spearman rank correlation. Their prognostic factors on disease free survival(DFS) and overall survival(OS) were guaranteed by Kaplan-Meier and Cox regression analyses. The detection of the levels of vascular endothelial growth factor and CD34 was fulfilled in 90 cases of HCC. Results: TRAF4 expression was both significantly higher in HCC than in surrounding non-tumor tissues(57.8% vs. 22.2 %; P0.001) and significantly correlated with tumor size and tumor staging. High TRAF4 was correlated with reduced DFS rate(P=0.001) and overall OS rate(P0.001) and were displayed in Kaplan-Meier survival analysis. Conclusions: TRAF4 is involved with multifarious clinicopathologic features.TRAF4 expression, as an independent adverse prognostic factor, DFS and OS in HCC, is associated with increased tumor angiogenesis. The combined detection of TRAF4 in locally advanced HCC is a trustworthy predictive factor for the tumor development and recurrence.     

The prognostic value of circulating plasma DNA level and its allelic imbalance on chromosome 8p in patients with hepatocellular carcinoma

Purpose: We demonstrated that chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma (HCC). This study assesses the value of circulating plasma DNA level and its allelic imbalance (AI) on chromosome 8p in the prediction of HCC prognosis. Methods: Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. The HCC and adjacent non-tumor liver tissues were obtained from surgical specimens. Plasma DNA was extracted and quantified. Two microsatellite markers on chromosome 8p, D8S258 and D8S264, were selected and used in the AI analysis. Results: The circulating plasma DNA level was found to closely associate with tumor size (P=0.008) and TNM stage (P=0.040), negatively associate with the 3-year disease-free survival (DFS) (P=0.017) and overall survival (OS) (P=0.001). AI at D8S258 in plasma DNA was significantly correlated with tumor differentiation (P=0.050), TNM stage (P=0.010), and vascular invasion (P=0.023), negatively correlated with the 3-year DFS (P=0.005) and OS (P=0.036). However, AI at D8S264 was only closely associated with 3-year DFS (P=0.014). Combined detection of AI at D8S258 and circulating plasma DNA level was independently associated with DFS (P=0.018) and OS (P=0.002) of patients with HCC. For patients with both AI at D8S258 and a higher level of plasma DNA, the 3-year DFS and 3-year OS rates were decreased remarkably (P=0.014 and 0.044). Conclusion: Combination of circulating plasma DNA level and AI at D8S258 might be an independent predictor for prognosis of HCC patients.     

Prognostic significance of p53 overexpression after hepatic resection of hepatocellular carcinoma.

BACKGROUND/AIMS: p53 mutation is the most common genetic abnormality in human cancers. However, although it has been reported that p53 overexpression in hepatocellular carcinoma (HCC) is associated with the aggressive behavior of tumor, the prognostic significance of p53 overexpression in HCC remains controversial. The aims of the present study were to examine the correlations between p53 overexpression and the clinicopathologic parameters of HCCs, and to determine the prognostic significance of p53 overexpression in HCC. METHODS: Immunohistochemical analysis of p53 overexpression was performed in 105 consecutive cases of HCC who underwent curative hepatic resection. Survival curves were calculated using the Kaplan-Meier method and multivariate analysis of outcome predictors for HCCs was assessed by logistic regression analysis. RESULTS: p53 overexpression was observed in 20 of 105 HCCs (19.0%). Multivariate analysis identified significant correlations between p53 overexpression and microvascular invasion (p=0.027), liver cirrhosis (p=0.035), 1-year survival rate (p=0.016), multiple tumors (p=0.014), and the presence of tumor capsule (p=0.010). The 2-year survival rate was poorer in patients without tumor capsule (p=0.043). CONCLUSIONS: Our results show a positive association between p53 overexpression and microvascular invasion in HCC, and indicate that p53 overexpression is a poor prognostic factor of survival, especially within 1 year after liver resection in HCC patients.     

Surgical resection for advanced hepatocellular carcinoma according to Barcelona Clinic Liver Cancer (BCLC) staging

Purpose

The BCLC staging classification has been widely endorsed to predict the prognosis of patients with HCC. However, its validity as a means of therapeutic instructions needs to be challenged. This study aimed to evaluate perioperative and long-term outcomes of surgical resection in patients with advanced hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer (BCLC) staging.

Methods

This study used a prospectively maintained database consisting of a consecutive series of 511 Chinese patients with advanced HCC who underwent surgical resection in a hepatobiliary surgical center from 2001 to 2007. Mortality, morbidity, long-term overall survival (OS) and disease-free survival (DFS) were evaluated.

Results

Hospital mortality was 2.3%, and overall morbidity was 31.3%. After a median follow-up period of 27.8?months (range, 0–112?months), the 1-, 3- and 5-year OS rate was 69.9, 41.2 and 30.5%, and the 1-, 3- and 5-year DFS rate was 48.2, 30.3 and 24.0%, respectively. The 1-, 3- and 5-year OS and DFS rates were significantly poorer in patients with vascular invasion and/or extrahepatic spread than those in patients without (both P?P?Conclusions Surgical resection could be considered in part of patients with advanced HCC (BCLC stage C), with low mortality, acceptable morbidity and favorable survival benefits. These results imply that BCLC recommendations for treatment schedules of advanced HCC need to be re-evaluated.     

Prognostic factors and long-term outcomes of hilar cholangiocarcinoma:A single-institution experience in China

AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution.METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival(OS) and disease-free survival(DFS) were evaluated by univariate and multivariate analyses.RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio(HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease(HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation(HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion(HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins(HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease(HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation(HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion(HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins(HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio(OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter(OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures(OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage(OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion(OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumorfree margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent factors for OS and DFS. Surgical procedures can indirectly affect survival outcome by influencing the tumor resection margin.     

Do the existing staging systems for primary liver cancer apply to combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma?

Background:The incidence of combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma(c HCC-ICC) is relatively low,and the knowledge about the prognosis of c HCC-ICC remains obscure.In the study,we aimed to screen existing primary liver cancer staging systems and shed light on the prognosis and risk factors for c HCC-ICC.Methods:We retrospectively reviewed 206 c HCC-ICC patients who received curative surgical resection from April 1999 to March 2017.The correlation of survival measures with the histological types or with tumor staging systems was determined and predictive values of tumor staging systems with c HCC-ICC prognosis were compared.Results:The histological type was not associated with overall survival(OS)(P = 0.338) or disease-free survival(DFS)(P = 0.843) of patients after curative surgical resection.BCLC,TNM for HCC,and TNM for ICC stages correlated with both OS and DFS in c HCC-ICC(all P 0.05).The predictive values of TNM for HCC and TNM for ICC stages were similar in terms of predicting postoperative OS(P = 0.798) and DFS(P = 0.191) in c HCC-ICC.TNM for HCC was superior to BCLC for predicting postoperative OS(P = 0.022) in c HCC-ICC.Conclusion:The TNM for HCC staging system should be prioritized for clinical applications in predicting c HCC-ICC prognosis.     

Morphologic classification of microvessels in hepatocellular carcinoma is associated with the prognosis after resection

Background and Aim: The relationship between neovasculature in hepatocellular carcinoma (HCC) and the prognosis of patients still remains controversial. The aim of the present study was to investigate the prognostic significance of morphologic features of the microvessels in patients with HCC after resection. Methods: The paraffin‐embedding specimens of 98 consecutive HCC patients, who received primary resection between 2000 and 2002, were collected from our prospective established tumor bank. The intratumoral microvessels were evaluated by immunohistochemical staining for CD31 and CD34. The disease‐free survival (DFS) and overall survival (OS) of patients were analyzed by Kaplan–Meier analysis and Cox proportional hazards regression model. Results: There are two distinct microvessel types: capillary‐like and sinusoid‐like were identified in tumor tissues. The patients could be divided into two groups according to their microvessel types. Both DFS and OS of capillary group patients (n = 65) were better than those of sinusoid group patients (n = 33). Multivariate analyses showed that the microvessel type was an independent risk factor for DFS (P = 0.016) and OS (P = 0.004) of this cohort. Capillary‐like microvessels were more common in small HCC, and were significantly associated with higher microvessel density, while sinusoid‐like microvessels were significantly correlated with lower microvessel density. Conclusions: The results of our study suggested that the microvessel type is an effective predictor of survival in patients with HCC after resection, which might serve as potential novel therapeutic targets for prevention of the recurrence of HCC after resection.