Evaluation of predictive value of CLIP, Okuda, TNM and JIS staging systems for hepatocellular carcinoma patients undergoing surgery

BACKGROUND: An accurate staging system is required to assess hepatocellular carcinoma (HCC) patients in order to benefit from hepatic resection before surgery. Cancer of the Liver Italian Program (CLIP) score was considered to be better than the Okuda staging system to predict survival. Japan Integrated Staging Score (JIS score) includes tumor, nodes, metastases (TNM) stage and Child-Pugh grade as a new staging system for HCC. The purpose of the present paper was to compare the CLIP, Okuda, TNM and JIS staging systems for HCC patients undergoing surgery. METHODS: From 1991 to 1995, 599 patients undergoing hepatic resection for HCC from four medical centers in Taiwan were evaluated. All patients were classified by Okuda, CLIP, TNM and JIS systems. Factors associated survivals were analyzed. RESULTS: There was no statistical difference in survival between CLIP 0 and 1 patients, or among CLIP 2-4 patients. The prognostic validation of the Okuda and CLIP scoring systems in discriminating survival in HCC patients undergoing surgery was not satisfied. The TNM system was successful in predicting survival for HCC patients undergoing surgery. The JIS score could also differentiate survivals for those patients except for JIS 3. By multivariate analysis, age > or =60 years old, serum albumin <3.5 g/dL, tumor size >5 cm and TNM stage were associated with survival. CONCLUSION: Both the Okuda and CLIP systems are not superior to TNM staging for HCC patients who undergo surgical resection. Whether JIS score is feasible for those patients with advanced HCC needs further evaluation.     

Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre

BACKGROUND: Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring systems) in a large series of cirrhotic patients with HCC undergoing non-surgical treatment in terms of their ability to classify patients into different risk groups METHODS: We retrospectively studied 268 Italian patients with HCC. A total of 146 patients were treated with ablation, 132 with percutaneous ethanol injection, and 14 with radiofrequency ablation; 103 underwent transcatheter arterial chemoembolisation and 19 had supportive care alone. Factors determining survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, CLIP, and BCLC scores evaluated before treatment were applied. RESULTS: Median survival was 25.7 months. In a multivariate analysis, portal vein thrombosis, alpha fetoprotein, total bilirubin, and tumour size were significant predictors of survival. Okuda, CLIP, and BCLC scores were all able to predict survival (p<0.001). They identified two, four, and six risk groups, respectively, with a median survival ranging from 27 to 19 months for Okuda, 30 to 5 months for CLIP, and 43 to 7 months for BCLC. CONCLUSIONS: Both CLIP and BCLC scores were more effective than the Okuda score in stratifying patients into different risk groups with early-intermediate HCC. However, the BCLC scoring system gave a better prediction of prognosis in patients with disease diagnosis at a very early stage.     

Tumour staging, morphology and p53 overexpression concur in predicting survival in hepatocellular carcinoma

BACKGROUND/AIMS: The prognosis of hepatocellular carcinoma (HCC) on cirrhosis is hard to predict as it depends on tumour stage, underlying liver disease, type of treatment and, possibly, biological factors of the tumour itself. METHODS: We prospectively evaluated the survival of 91 consecutive patients with HCC on cirrhosis, diagnosed between January 1998 and December 1999. Clinical features and histological/biological aspects, including histotype, grade, p53 overexpression, cytoproliferation and apoptotic markers were analysed. RESULTS: Child-Pugh (P = 0.01), Okuda (P < 0.0001), Cancer of the Liver Italian Program (CLIP) staging (P < 0.0001) and type of treatment (P = 0.0001) were significantly related to survival. In the Cox model, CLIP staging was included as independent predictor of survival at step 1 (P < 0.0001) with Okuda at step 2 (P = 0.013). Amongst the biological factors, p53 overexpression and histotype were significantly related with survival (P = 0.0044 and 0.017 respectively). When clinical and biological variables were examined together in the Cox model, CLIP and Okuda were confirmed as being statistically related with survival (P < 0.0001 and =0.012) followed by histotype and p53 overexpression (P = 0.019 and 0.02). CONCLUSIONS: CLIP, Okuda, histotype and p53 overexpression are the strongest predictors of survival in this series of patients. These data confirm that staging of the tumour and underlying liver disease are strictly related to prognosis but support the concurrent role of clinical and biological factors in upgrading our capacity of predicting the fate of HCC patients.     

Prognostic factors and survival according to the Okuda stage in patients with hepatocellular carcinoma]

BACKGROUND/AIMS: There are several staging systems to decide the stage of hepatocellular carcinoma (HCC), but yet incomplete. Okuda stage which includes both tumor characteristics and liver function is widely used. The aims of this study were to assess the usefulness of known prognostic factors and Okuda staging system in 237 cases of HCC. METHODS: A retrospective analysis of 237 cases of HCC diagnosed from 2000 to 2002 was performed. We analyzed prognostic factors such as age, sex, liver cirrhosis, Child-Pugh classification, tumor size, albumin, bilirubin, alpha-FP, ascites, encephalopathy and Okuda stage. Prognostic analysis was performed for single variables and estimating survival distributions were analyzed by the Kaplan-Meier method, statistically compared by the log-rank test. RESULTS: Patients had a mean age of 57.5 years and were predominantly men (79.7%). Liver cirrhosis were noticed in 214 cases (90.3%). The overall median survival period was 25.7 months. The median survival period was correlated to bilirubin, ascites, alpha-FP, tumor size, and Child-Pugh classification, but not to age, sex, and pattern of viral infection. The median survival period of the Okuda stage I, II and III cases was 35.8, 11.9 and 8.5 months (p<0.001). CONCLUSIONS: The median survival period of patients with HCC is significantly correlated to Okuda staging system, and survival period has improved than the initial data when the Okuda staging system was published in 1985. However, in order to discriminate early staged HCC more accurately, other prognostic factors such as alpha-FP and tumor morphology should be included in future staging system for HCC.     

Prognostic factors for survival in patients with hepatocellular carcinoma after radiofrequency ablation]

BACKGROUND/AIMS: Currently there is no consensus on which staging system is the best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aim of this study was to identify independent factors to predict survival and to compare 4 available prognostic staging systems in patients with early HCC after radiofrequency ablation. METHODS: We retrospectively studied 100 Korean patients with early HCC. Prognostic factors for survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, Cancer of the Liver Italian Program (CLIP), TNM and Japanese integrated staging score (JIS score) were evaluated before the treatments. RESULTS: Overall survival rates of 12, 24 and 36 months were 89%, 76%, and 64% respectively and the mean survival duration was 45 months. Multivariable analysis showed that albumin, total bilirubin and size of tumor were independent prognostic factors. Multivariate analysis showed that TNM and JIS score staging systems were significant staging systems for the prediction of prognosis. CONCLUSIONS: Both TNM and JIS score are more effective than the Okuda and CLIP staging systems in stratifying patients into different risk groups with early HCC. However, JIS score gives better prediction of prognosis in patients with HCC after radiofrequency ablation.     

Value of the model for end-stage liver disease for predicting survival in hepatocellular carcinoma patients treated with transarterial chemoembolization

Objective. The aim of this study was to evaluate the prognostic value of the model for end-stage liver disease (MELD) and its modified forms, and to compare these scoring systems with other staging systems for hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). Material and methods. A total of 325 patients who underwent TACE for the initial treatment of HCC between January 2000 and May 2007 were enrolled in the study. Before TACE was carried out, MELD, MELD-Na, Child-Pugh score, Okuda stage, CLIP score, JIS score, BCLC stage, and UICC stage were checked. After one month, ?MELD and ?MELD-Na were calculated. Results. Mean MELD/MELD-Na/?MELD/?MELD-Na scores were 7.5±3.7, 8.0±4.7, ?0.2±3.5 and 0.04±4.5, respectively. MELD (p=0.009) and MELD-Na (p=0.017) significantly correlated with survival, but ?MELD and ?MELD-Na did not (p >0.05). The Child-Pugh score and other staging systems correlated significantly with survival (p <0.05). The AUROC values for 3, 12, and 36 months’ survival were 0.633, 0.545, and 0.615 for MELD; 0.655, 0.555, and 0.612 for MELD-Na; 0.639, 0.616, and 0.691 for Child-Pugh score; 0.714, 0.662, and 0.717 for the Okuda score; 0.837, 0.86, and 0.792 for the CLIP score; 0.859, 0.814, and 0.808 for the JIS score; 0.846, 0.833, and 0.749 for BCLC stage; and 0.878, 0.812, and 0.735 for UICC stage, respectively. Conclusions. MELD and MELD-Na showed good correlations with survival, especially for patients with early-stage disease. However, these were not superior to those of other staging systems or Child-Pugh score. These parameters should only be used as supportive data.     

Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. The Cancer of the Liver Italian Program (CLIP) Investigators

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage. As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with HCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection.     

Staging of hepatocellular carcinoma: assessment of the CLIP,Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto

BACKGROUND: A new staging system for hepatocellular carcinoma (HCC) has recently been reported from Italy (CLIP classification). It combines Child-Pugh staging with tumour criteria: tumour morphology, portal invasion, and alpha fetoprotein levels. AIMS: To validate the use of the CLIP staging in a cohort of HCC patients and compare it with Okuda staging. PATIENTS AND METHODS: A retrospective analysis of patients with HCC diagnosed in the Toronto General Hospital between October 1994 and December 1998. RESULTS: A total of 313 patients were identified; 19 patient with insufficient data and 37 transplant patients were excluded. Hence 257 patients in whom complete data for clinical staging were available were included in the study. The median survival of the cohort was 22.8 months. The CLIP stage 0 group (23.1% of the cohort) and the Okuda stage 1 group (50.7% of the cohort) had a five year survival rate of 67% and 35%, respectively (p<0.02). The CLIP stage 0 criteria more accurately defined patients with a good prognosis. The Okuda classification failed to identify two thirds of the 37 patients with a poor prognosis, who were identified by the CLIP criteria. Patients with a CLIP score > or =4 shared a very poor prognosis (median survival 1-3 months). Further classification above stage 4 was unnecessary. SUMMARY: The CLIP classification for HCC is easy to implement and more accurate than the Okuda classification. Our cohort was different from the CLIP cohort (more hepatitis B) but the results were still consistent.     

Transcatheter arterial chemoembolization therapy for patients with hepatocellular carcinoma: a case-controlled study.

BACKGROUND & AIMS: Transcatheter arterial chemoembolization (TACE) currently is used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its efficacy still is debated. Our aim was to assess the impact of TACE on patient survival and to identify prognostic factors for survival. METHODS: Fifty-six cirrhotic patients with unresectable HCC undergoing at least 1 course of TACE were matched 1:1 for sex, age (in 5-year periods), parameters of Child-Pugh score, Okuda stage, and tumor type with a control group who had received only supportive care. RESULTS: The 2 groups were comparable for cause of cirrhosis, alpha-fetoprotein serum levels, and Cancer of the Liver Italian Program (CLIP) score. The 56 patients in the TACE group received a total of 123 treatment courses. The median follow-up period was 16 months (range, 1-67 mo) in the TACE group and 5 months (range, 1-77 mo) in the supportive care group. Survival rates at 12, 24, and 30 months in patients receiving TACE were 74.3%, 52.1%, and 38.8%, respectively, with a median survival time of 25 months, whereas in supportive care patients the rates were 39.4%, 25.4%, and 19%, respectively, with a median survival time of 7 months (P = .0004). At univariate analysis, TACE, tumor type, presence of ascites, alpha-fetoprotein serum level, CLIP score, and Okuda stage were associated significantly with survival. Only TACE and CLIP score proved to be independent predictors of survival at multivariate analysis. CONCLUSIONS: TACE is an effective therapeutic option for cirrhotic patients with unresectable HCC and a CLIP score of 3 or less.     

Prognosis of a large cohort of patients with hepatocellular carcinoma in a single European centre

BACKGROUND/AIM: Only a few follow up data are available for patients with hepatocellular carcinoma (HCC) in Europe and the USA. Therefore, we analysed all HCC patients admitted to our hospital between 1988 and 1999. METHODS: We documented aetiology, stage (HCC: Okuda and UICC classifications, liver cirrhosis: Child-Pugh score), and diagnostic and therapeutic measures of 281 consecutive HCC patients. Survival time was calculated as a function of staging and therapy. RESULTS: Cirrhosis was diagnosed in all patients. Seventy-two patients underwent liver resection, 28 liver transplantation, 31 transarterial chemoembolization and 14 percutaneous ethanol injection. One hundred and thirty-six patients received no treatment. The Okuda and the Child-Pugh classification predicted a significant decrease of median survival time, whereas the UICC classification was less powerful. CONCLUSIONS: HCC occurred only in patients with liver cirrhosis. Survival time correlated with therapy (or no therapy) and with the Child-Pugh Score. In European patients the Okuda classification is superior to the UICC classification and should be compared to novel classification systems.     

An independent evaluation of modern prognostic scores in a central European cohort of 120 patients with hepatocellular carcinoma

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is a common cancer worldwide. As prognosis of HCC patients depends not only on tumour extension but also on liver function, TNM staging of HCC is of limited value. The Okuda score incorporating the variables of liver function and tumour extension is used widely. However, among patients with an intermediate Okuda score, survival varies considerably. Several newer scores promise to perform better than the Okuda score in stratifying HCC patients. We therefore tested the ability of several newer scores to predict survival in comparison to the Okuda score in a European cohort of HCC patients. PATIENTS AND METHODS: A total of 120 patients with sufficient follow-up data were identified retrospectively among the 130 patients with HCC first seen between 1997 and 2000 in our department. Child-Pugh score, Okuda score, Vienna survival model for HCC (VISUM-HCC) score, Chevret score, Barcelona clinic liver cancer (BCLC) classification and cancer of the liver Italian programme (CLIP) score were calculated. Survival analysis was performed for all eligible patients stratified according to each scoring system. Receiver operating characteristics analysis was performed using six months survival as the outcome measure. Univariate and stepwise logistic regression analyses were performed to identify prognostic factors. RESULTS: Survival times of HCC patients grouped according to all scores were significantly different. All scores performed similarly to the Okuda score in the receiver operating characteristic analysis. Prognostic factors for survival were albumin concentration and the presence of portal obstruction. CONCLUSION: In our central European cohort, there was no advantage of using the newer scores instead of the Okuda score.     

Clinical usefulness of ^18F-FDG PET/CT in the restaging of esophageal cancer after surgical resection and radiotherapy

AIM： To evaluate the clinical usefulness of lSF-fluorodeoxyglucose positron emission and computed tomography QSF-FDG PET/CT） in restaging of esophageal cancer after surgical resection and radiotherapy. METHODS： Between January 2007 and Aug 2008, twenty histopathologically diagnosed esophageal cancer patients underwent 25 PET/CT scans （three patients had two scans and one patient had three scans） for restaging after surgical resection and radiotherapy. The standard reference for tumor recurrence was histopathologic confirmation or clinical follow-up for at least ten months after ^18F-FDG PET/CT examinations. RESULTS： Tumor recurrence was confirmed histopathologically in seven of the 20 patients （35%） and by clinical and radiological follow-up in 13 （65%）. ^18F-FDG PET/CT was positive in 14 patients （68.4%） and negative in six （31.6%）. ^18F-FDG PET/CT was true positive in 11 patients, false positive in three and true negative in six. Overall, the accuracy of ^18F-FDG PET/CT was 85%, negative predictive value （NPV） was 100%, and positive predictive value （PPV） was 78.6%.The three false positive PET/CT findings comprised chronic inflammation of mediastinal lymph nodes （n = 2） and anastomosis inflammation （n = 1）. PET/ CT demonstrated distant metastasis in 10 patients. ^18F-FDG PET/CT imaging-guided salvage treatment in nine patients was performed. Treatment regimens were changed in 12 （60%） patients after introducing ^18F-FDG PET/CT into their conventional post-treatment follow-up program. CONCLUSION： Whole body ^18F-FDG PET/CT is effective in detecting relapse of esophageal cancer after surgical resection and radiotherapy. It could also have important clinical impact on the management of esophageal cancer, influencing both clinical restaging and salvage treatment of patients.     

Prognostic factors for survival in patients with unresectable hepatocellular carcinoma undergoing chemoembolization with doxorubicin drug-eluting beads: a preliminary study

Background:

Transarterial chemoembolization (TACE) with drug-eluting beads (DEB) is a new treatment modality. Little is known about prognostic factors affecting survival after DEB TACE for patients with hepatocellular carcinoma (HCC).

Methods:

Patients who underwent TACE with doxorubicin DEB for unresectable HCC during 2006–2008 were studied. Survival was calculated from the day of first transcatheter therapy. Survival analysis was performed using Kaplan–Meier estimations. Survival curves were compared using the log-rank test.

Results:

Fifty patients underwent chemoembolization with doxorubicin DEB. They included 39 women and 11 men, with a median age of 57.5 years (range 28–91 years). Eighteen patients died during the study period and 32 remained alive. Overall survival rates at 6 months, 1 year and 2 years from the first administration of doxorubicin DEB TACE were 71%, 65% and 51%, respectively. Prognostic factors found to be significant on univariate analysis were Child–Pugh class, Okuda staging, bilirubin > 2 mg/dl, albumin < 3.0 g/dl, Model for End-stage Liver Disease (MELD) score, serum alphafetoprotein (AFP), Cancer of the Liver Italian Programme (CLIP) score, tumour satisfying Milan criteria, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and Barcelona Clinic Liver Cancer (BCLC) staging.

Conclusions:

Child–Pugh class, Okuda staging, bilirubin > 2 mg/dl, albumin < 3 g/dl, MELD score, serum AFP, CLIP score, Milan criteria, ECOG PS and BCLC staging were found to be prognostic markers of survival after treatment with doxorubicin DEB TACE in patients with unresectable HCC.     

Prognosis of hepatocellular carcinoma in anti-HCV positive cirrhotic patients: a single-centre comparison amongst four different staging systems

BACKGROUND: Epidemiological studies have foreseen an increase in the incidence of hepatocellular carcinoma (HCC) in the near future and it is estimated that this trend will mostly affect hepatitis C virus (HCV) positive cirrhotic patients. Therefore, accuracy of HCC staging is an important clinical issue. AIM: To investigate the prognostic usefulness of a series of newly proposed HCC prognostic systems such as the Cancer of the Liver Italian Program (CLIP) score, the Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire (GRETCH) model and the Barcelona Clinic Liver Cancer (BCLC) staging classification when compared with the usefulness of a known staging system such as the Okuda staging system in a group of anti-HCV positive cirrhotic patients with HCC seen at a single centre. METHODS: Okuda stage, CLIP score, GRETCH model and BCLC stages were retrospectively computed in 81 anti-HCV positive cirrhotic patients with HCC. We evaluated and compared the ability of these methods to assess survival prognosis. RESULTS: As of December 2001, 51 patients had died and overall median survival was 18 months. All the staging systems were able to identify various patient subgroups with different survival. The CLIP score, the GRETCH model and the BCLC staging classification were better at characterizing the 1-year prognosis of the patients when compared with the Okuda staging system, whilst the 3-year prognostic evaluation was improved only by using the CLIP score or the BCLC staging classification. CONCLUSIONS: The prognostic value and usefulness of the CLIP score, the GRETCH model and the BCLC staging classification was reproduced in a single-centre analysis of anti-HCV positive HCC cirrhotic patients. These scores provided a prognostic assessment of our patients which is superior to what was obtained by the Okuda staging system.     

Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients. Cancer of the Liver Italian Program

To reliably estimate the prognoses of patients with hepatocellular carcinoma (HCC), both liver function and tumor-related factors should be accounted for. However, there are few worldwide staging systems that assess prognostic value in the context of selecting individual patients for randomized stratification in therapeutic and clinical trials. We investigated the value of known prognostic systems and verified the usefulness of the new scoring system proposed by the Cancer of the Liver Italian Program (CLIP), as determined from 662 Japanese patients. A retrospective analysis of the HCC diagnoses at 4 Japanese institutions from 1990 and 1998 was performed. Overall survival was the only end point used in the analysis. Discriminatory ability and predictive power of the CLIP score were compared with those of Okuda stage and AJCC TNM stage. Compared with the Okuda and AJCC staging systems, the CLIP score's enhanced discriminatory capacity, which was tested by the linear trend test and Harrels' c-index, revealed a class of patients with an impressively more favorable prognosis and another class with a relatively shorter life expectancy. Moreover, the likelihood ratio test showed that the CLIP score had additional homogeneity of survival within each score above that of the Okuda stage or the AJCC stage. This was true for 3 subgroups of patients who received surgery, transcatheter arterial chemoembolizations, and percutaneous ethanol injections. Collectively, these findings indicate that the CLIP score has the highest stratification ability with regard to prognosis in patients with HCC. The CLIP score could be used internationally to stratify randomization groups in therapeutic and clinical trials.     

Comparison of seven staging systems in cirrhotic patients with hepatocellular carcinoma in a cohort of patients who underwent radiofrequency ablation with complete response

BACKGROUND AND AIMS: Many staging systems for hepatocellular carcinoma (HCC) have been proposed but the best tool for staging of HCC remains controversial. The aim of the present study was to identify the best staging system evaluating the predictive ability for outcome for each of the seven different staging systems applied in a homogeneous group of patients who underwent percutaneous radiofrequency ablation (RFA). METHODS: We analyzed retrospectively 112 patients with HCC and cirrhosis treated with percutaneous RFA from January, 1998 to April, 2005. Response to treatment after 30 days and for long-term follow-up was evaluated with computed tomography (CT) or magnetic resonance imaging (MRI) and serum alpha-fetoprotein level (AFP). All of the 112 patients were grouped according to each one of the seven different staging systems: Okuda, TNM, BCLC, CLIP, GRETCH, CUPI, JIS. RESULTS: The mean follow-up time of the 112 patients submitted to RFA was 24 months (range 3-92 months) with survival rates at 1, 3, and 5 yr of 82%, 40%, and 18%, respectively. Univariate and multivariate analyses showed that factors related to survival were Child-Pugh score (P相似文献   

Presentación,clasificación y evolución de los pacientes con carcinoma hepatocelular en un centro de Veracruz,México

BackgroundHepatocellular carcinoma (HCC) staging provides a basis for calculating disease prognosis and therapeutic guidance. Liver resection and transplantation are curative options, and ablation therapies are applied to patients that are not candidates for curative treatment. Survival after liver resection or ablation therapies varies.AimsTo describe the presentation, staging, management, and outcome in patients with HCC in our center.Patients and methodsForty-two patients had a 7-year prospective follow-up. Survival was calculated with the Kaplan-Meier analysis and the log-rank test was used for its comparison between the staging systems (Okuda, BCLC, and CLIP) and types of treatment (liver resection, radiofrequency ablation, and no surgical treatment).ResultsThe mean age of the patients was 68.9 ± 9.5 years; 57% were women. A total of 54% of the patients presented with cirrhosis and 31% were infected with hepatitis C virus (HCV). The mean tumor size was 6.48 ± 2.52 cm. The CLIP 0, Okuda I, and BCLC A stages had better survival rates than the other stages (P<0.05). Survival with resection was superior (median of 32 months and survival at 1, 3, and 5 years of 83, 39, and 19.7%, respectively) to that of both radiofrequency ablation (median of 25 months and survival at 1 and 3 years of 90 and 17.2%, respectively) and no surgical treatment (1 year < 5%) (P<0.05).ConclusionThe patients at our center were diagnosed at late stages of HCC, as is the case in other Mexican populations. Outcome in relation to CLIP and BCLC was similar to the prognoses reported in the literature. The best results were observed in the patients with early stage disease and those that underwent HCC resection surgery.     

Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations,and a proposal for a new staging system,the Japan Integrated Staging Score (JIS score)

A clinical staging system for cancer patients provides guidance for patient assessment and making therapeutic decisions. It is useful in deciding whether to treat a patient aggressively, and in avoiding the overtreatment of patients who would not tolerate the treatment or patients whose life expectancy rules out any chance of treatment. Clinical staging is also an essential tool for comparison between groups in therapeutic trials and for comparison between different studies. The current classifications most commonly used for hepatocellular carcinoma (HCC) are the Okuda stages, the Child-Pugh staging system, tumor node metastasis (TNM) staging, and the Cancer of the Liver Italian Program (CLIP) score. Among these, the CLIP score is currently the most commonly used integrated staging score, including both tumor stage and liver disease stage. Although the CLIP score has been well validated by many authors in terms of its prognostic value in HCC patients, this score has some problems and limitations when applied to currently diagnosed HCC patients, who are diagnosed in the early stage of disease. First, the CLIP score can discriminate score 0- to 3-patient populations, but it is not able to discriminate score 4- to 6-patient groups. Second, the definition of tumor morphology in the best prognostic group is too advanced, i.e., uninodular and a tumor extent of less than 50% of the liver. As a result, the prognosis of the CLIP system best prognostic group is not so good. In other words, this system cannot identify the best prognostic group who would benefit from curative and aggressive treatment. Third, nearly 80% of the patient population is classified as having a CLIP score of 0–2, as confirmed by many studies, which shows poor stratification ability. In contrast, a new staging system based on the Liver Cancer Study Group of Japan (LCSGJ), the Japan Integrated Staging (JIS) score is currently proposed in Japan. This staging system combines Child-Pugh grade (grade A, score 0; grade B, score 1; grade C, score 2) and TNM staging by the LCSGJ criteria (stage I, score 0; stage II, score 1; stage III, score 2; stage IV, score 3). The stratification ability of the JIS scoring system is much better than that of the CLIP scoring system. The JIS scoring system also performed better than the CLIP scoring system in selecting the best prognostic patient group. The cumulative 10-year survival rates of the best prognostic groups in the CLIP staging system (CLIP score 0) and JIS staging system (JIS score 0) were 23% and 65%, respectively (P < 0.01). All scoring systems arise as a compromise between simplicity and discriminatory ability. We confirmed that the JIS score increases predictive efficacy, while remaining simple compared with the CLIP score. Because the JIS score is quite easily obtained and is objective, we strongly propose it for widespread use as a prognostic staging system for HCC in clinical practice. Received: December 19, 2002 / Accepted: December 19, 2002 Reprint requests to: M. Kudo     

Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy

Background We previously reported the effectiveness of the modified Cancer of the Liver Italian Program (CLIP) score in hepatocellular carcinoma (HCC) staging. To determine the best predictive staging system for HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 230 Japanese HCC patients following hepatic resection. Methods We compared overall survival as predicted by different staging systems: the tumor node metastasis (TNM) system by the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), the modified JIS score using liver damage grade, the CLIP score, and our modified CLIP score using protein induced by vitamin K absence or the antagonist II (PIVKA-II). Results By a univariate analysis the PIVKA-II level (cut-off level, 400 mAU/ml) was significantly associated with patient survival (P = 0.031); however, alpha-fetoprotein level was not related to survival. Liver damage grade was significantly associated with patient survival (P = 0.039), although Child-Pugh classification was not related to survival. Univariate analysis showed that prediction of survival, according to disease stage, was better with the modified JIS score than with the TNM system, CLIP, modified CLIP, or JIS score. Multivariate analysis showed the modified JIS score showed the best ability to predict overall survival according to disease stage (Hazard ratio, 1.77; P = 0.002), and its Akaike information criteria statistic was the lowest (634.3). Conclusions The modified JIS score, a staging system that combines tumor factors and hepatic function, is a better predictor of prognosis than other systems in HCC patients who have undergone hepatic resection.     

Cancer of the Liver Italian Program score helps identify potential candidates for transarterial chemoembolization in patients with Barcelona Clinic Liver Cancer stage C

BACKGROUND: The Barcelona Clinic Liver Cancer(BCLC)staging system for hepatocellular carcinoma(HCC) recommends transarterial chemoembolization(TACE) as the first line therapy for stage B patients and sorafenib treatment for stage C patients.However, stage C patients exhibit variations in terms of tumor burden, liver function, and extrahepatic metastasis, which could potentially affect disease outcome. Here, we assessed whether the Cancer of the Liver Italian Program(CLIP) scores can help identify stage C patients likely to benefit from TACE.METHODS: Out of 295 BCLC stage C HCC patients enrolled between January 2009 and December 2011, those with platelet counts 30×10~9 cells/L, total bilirubin 51 μmo L/L, and an unobstructed main portal vein were scheduled for TACE(n=195). The remaining patients received best supportive care(BSC, n=100).All the patients were followed up for symptoms, performance status, and Child-Pugh classification scores every 4 weeks until death or December 2013. The prognosis of each group was evaluated by using the log-rank test and Cox-Mantel test.RESULTS: The median overall survival(OS) was 6 months [95% confidence interval(CI): 4.64-7.36]. The OS was 9 months for the TACE group and 4 months for the BSC group. The TACE group had a longer OS than the BSC subgroup for CLIP scores 0-2 [13 months(95% CI: 8.55-17.45) vs 4 months(95% CI:0.00-10.96), P=0.001]. No significant differences were found between the TACE and BSC groups for CLIP scores 3-5. The CLIP score and treatment methods were found to be independent prognostic factors.CONCLUSIONS: BCLC stage C HCC patients exhibit definite disease heterogeneity and can be reclassified by using the CLIP scoring system. Moreover, patients with CLIP scores 0-2 are likely to benefit from TACE. However, additional studies with long-term follow-up will be required to validate these findings.