Hepatocellular carcinoma in Central Europe: prognostic features and survival

Schöniger–Hekele, Maximilian; Müller, Christian; Kutilek, Mathilde; Oesterreicher, C.; Ferenci, Péter; Gangl, Alfred

doi:10.1136/gut.48.1.103

Cited by 215 publications

(179 citation statements)

References 38 publications

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“…30 Tumor burden had also been shown to be an important prognostic indicator, but the cutoff used in previous studies has varied from more than 5 cm diameter of the largest nodule to a tumor involving more than 50% of the liver. 31,32 As expected, patients who were eligible for some form of treatment had better survival than those who were too moribund for any treatment. Nevertheless, treatment in general significantly improved survival even after performance status, MELD score, portal vein thrombosis, and tumor size were controlled for.…”

Section: Discussionmentioning

confidence: 84%

Prognosis of hepatocellular carcinoma

et al. 2005

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Currently there is no consensus which staging system is best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aims of this study were to identify independent predictors of survival and to compare 7 available prognostic staging systems in patients with HCC. A total of 239 consecutive patients with cirrhosis and HCC seen between January 1, 2000, and December 31, 2003, were included. Demographic, laboratory, and tumor characteristics and performance status were determined at diagnosis and before therapy. Predictors of survival were identified using the Kaplan-Meir test and the Cox model. Sixty-two percent of patients had hepatitis C, 56% had more than 1 tumor nodule, 24% had portal vein thrombosis, and 29% did not receive any cancer treatment. At the time of censorship, 153 (63%) patients had died. The 1-and 3-year survival of the entire cohort was 58% and 29%, respectively. The independent predictors of survival were performance status (P < .0001), MELD score greater than 10 (P ‫؍‬ .001), portal vein thrombosis (P ‫؍‬ .0001), and tumor diameter greater than 4 cm (P ‫؍‬ .001). Treatment of HCC was related to overall survival. The Barcelona Clinic Liver Cancer (BCLC) staging system had the best independent predictive power for survival when compared with the other 6 prognostic systems. In conclusion, performance status, tumor extent, liver function, and treatment were independent predictors of survival mostly in patients with cirrhosis and HCC. The BCLC staging system includes aspects of all of these elements and provided the best prognostic stratification for our cohort of patients with HCC. ( H epatocellular carcinoma (HCC) is the fifth most common tumor worldwide. In the United States, the incidence of HCC has been rising, 1 and it is the tumor with the largest increase in incidence over the last 12 years. 2 Furthermore, the overall survival of patients with HCC has not improved over the last 20 years, with the incidence rate almost equal to the death rate. 3 It is projected that the increase in incidence of HCC will continue over the next 20 years in the United States. 4 Therefore, it is important to understand the factors that predict survival of patients with HCC.

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Section: Discussionmentioning

confidence: 84%

Prognosis of hepatocellular carcinoma

et al. 2005

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“…In previous reports, factors including the size and number of tumor nodules, micro/macrovascular invasion, and high serum AFP levels were associated with hepatocellular carcinoma recurrence after resection 3,12 and liver transplantation. 4 Similar to other investigators, we found that high serum AFP levels were associated with hepatocellular carcinoma recurrence.…”

Section: Discussionmentioning

confidence: 87%

“…6,7 Mutation of p53 has been implicated in the development of cancers of the breast, colon, lung, prostate, bladder, skin, as well as hepatocellular carcinoma. 6,[8][9][10][11][12] The Ki-67 protein is associated with active cell proliferation. It is expressed in all phases of the cell cycle, except G0, with the highest expression seen in G2/M.…”

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confidence: 99%

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients

et al. 2005

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Patients with hepatocellular carcinoma who undergo orthotopic liver transplantation (OLT) are at risk for posttransplant tumor recurrence. The aim of this study was to evaluate whether expression of p53 and Ki-67 in hepatocellular carcinoma lesions present in explanted liver tissue was associated with time to tumor recurrence after OLT. Subjects consisted of 20 consecutive patients who underwent OLT and were found to have hepatocellular carcinoma in the liver explant. Immunostaining for p53 and Ki-67 was performed by standard methods. The presence of nuclear immunostaining in 410% of the tumor tissue was considered positive. Time to recurrence of hepatocellular carcinoma after OLT was compared between patients with positive and negative immunostaining by the log rank test. Multivariate analysis was performed using a Cox regression model to control for potentially confounding clinical factors. Time to post-transplant hepatocellular carcinoma recurrence was significantly more rapid in p53 þ (P ¼ 0.0007) and Ki-67 þ cases (P ¼ 0.001). These associations remained significant in multivariate analysis. Furthermore, time to recurrent hepatocellular carcinoma was significantly shorter in patients with a serum alpha feto-protein (AFP) level Z100 ng/ml at time of diagnosis, compared to those with an AFP level o100 ng/ml (P ¼ 0.003). In conclusion, expression of p53 and Ki-67 in hepatocellular carcinoma lesions, and a serum AFP level Z100 ng/ml were associated with more rapid recurrence of hepatocellular carcinoma after OLT. Identification of patients at risk for early post-transplant recurrence could be used to guide surveillance and adjuvant treatment strategies.

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“…In one study involving 245 HCC cases, the median survival from the point of diagnosis was only 8 months (6). In another study of 336 patients, survival was as little as 0.7 months for stage III HCC versus 11.5 months for stage I tumors, with a median survival rate of 2.1 months (7).…”

Section: Introductionmentioning

confidence: 99%

pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular Carcinoma

Claudio

Russo

Kumar

et al. 2004

Clinical Cancer Research

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Hepatocarcinoma (HCC) is the fifth most common cancer, with more than one million fatalities occurring annually worldwide. Multiple risk factors are associated with HCC disease etiology, the highest incidence being in patients with chronic hepatitis B virus and hepatitis C virus, although other factors such as genetic makeup and environmental exposure are involved. Multiple genetic alterations including the activation of oncogenes and inactivation of tumor suppressor genes are required for malignancy in human cancers and are correlated with increased stages of carcinogenesis and further tumor progression. In this study of 21 HCC patients, we analyzed pRb2/p130, vascular endothelial growth factor (VEGF), p27 (KIP1) , and proliferating cell nuclear antigen as potential HCC molecular biomarkers. In our sample set, we found that p27 (KIP1) was absent. Univariate survival analysis showed that proliferating cell nuclear antigen expression (diffuse staining >50% of positive cells in tumor) was confirmed as a significant HCC prognostic biomarker for determining patient survival agreeing with previous studies (P ‫؍‬ 0.0126, log-rank test). Lower pRb2/p130 expression was associated to a borderline P value of inverse correlation with tumor malignancy and to a positive correlation with respect to the time from HCC diagnosis (Spearman coefficient ‫؍‬ 0.568; P < 0.05). Conversely, higher VEGF expression was associated with a poor survival (P ‫؍‬ 0.0257, log-rank test). We demonstrate for the first time that pRb2/p130 is inversely correlated with VEGF expression and tumor aggressiveness (P < 0.05) in p27 (KIP1) -negative HCC patients. pRb2/p130 and VEGF expression are independent from tumor staging, suggesting their possible role as independent prognostic molecular biomarkers in HCC. Furthermore, we have evidence that VEGF together with pRb2/p130 may act as new HCC biomarkers in a p27 (KIP1) -independent manner. Additional studies with larger numbers of patient data would allow the use of multivariable techniques and would be able to further identify patients with poorer survival.

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Hepatocellular carcinoma in Central Europe: prognostic features and survival

Abstract: Background and aims-We (Gut 2001;48:103-109)

Cited by 215 publications

References 38 publications

Prognosis of hepatocellular carcinoma

Prognosis of hepatocellular carcinoma

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients

pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular Carcinoma

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