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.     

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.     

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.     

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     

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.     

Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome

Background  Hepatocellular carcinoma (HCC) is uncommon in young adults. This study examined the clinical characteristics and survival outcome of young HCC patients compared with those in older patients. Methods  Data were prospectively collected from 638 patients diagnosed with HCC over a 9-year period. Patients aged ≤40 years at diagnosis of HCC were defined as young HCC patients. Their clinical characteristics and survival was compared with those aged >40 years. Results  The prevalence of young HCC was 8.6% (55/638). Young HCC patients had a significantly higher rate of hepatitis B-related disease (HBsAg positivity: 85.5% vs. 59.7%, P = 0.003), better Child-Pugh status (Child-Pugh class A: 69.1% vs. 43.9%, P = 0.002), and lower rates of cirrhosis (12.7% vs. 34.3%, P = 0.001) compared with the older group. They had more advanced disease at diagnosis, with higher α-fetoprotein levels (>12 000 μg/l: 45.4% vs. 30.5%, P = 0.026), a higher incidence of portal vein involvement (63.6% vs. 40%, P = 0.003), and a more advanced TNM stage (TNM IV: 83.6% vs. 66.4%, P = 0.018). More young patients were eligible for surgical resection (18.2% vs. 8.2%, P = 0.014). The overall survival between the two groups was similar, but when the patients were stratified for stage of disease, the median survival of young patients with early disease was superior to that of older patients (51.2 vs. 11.6 months, P = 0.025). Conclusions  HCC in young adults occurs mainly in hepatitis B carriers and is often diagnosed at an advanced stage. Their survival outcome is not different from that of older patients because the advanced disease at presentation offsets the advantages of better liver function and a higher resection rate. However, there is a distinct survival advantage for young patients diagnosed with early disease. These results support the importance of extending HCC surveillance to young hepatitis B carriers.     

Hepatocellular Carcinoma in Young Adults: The Clinical Characteristics, Prognosis, and Findings of a Patient Survival Analysis

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, HCC is rare in young Japanese patients and the clinical features of young patients with HCC have not yet been fully studied. This study was designed to determine the clinical characteristics and prognosis of patients with HCC who are younger than aged 40 years. A retrospective analysis was performed for patients newly diagnosed with HCC and observed from January 1990 to December 2003 at our hospitals. Patients younger than aged 40 years at the diagnosis of HCC were defined as the young group and were reviewed. There were 20 patients (16 males) with HCC who were younger than aged 40 years. The mean age at diagnosis was 33.6 (range, 20–39) years. Fifteen of 20 patients were positive for hepatitis B surface antigen (HBsAg) and 2 patients were positive for hepatitis C virus antibody. According to the Child-Pugh grading, the liver function was relatively good in all patients. Because most of the patients did not receive periodic follow-up, this disease often was discovered at an advanced stage, usually after the appearance of some symptoms. Although intensive treatment was performed for such young patients, the survival was nevertheless poor. Most patients died from this cancer within 1 year. However, one patient who received periodic follow-up and also was in relatively good physical condition had a better prognosis, and he survived for 88 months. Young patients with HCC tended to have a poor prognosis because of advanced stage of HCC, despite a well-preserved liver function and aggressive treatment. Screening for HCC and an early diagnosis is needed for such patients to demonstrate an improved prognosis, especially for HBsAg-positive patients.     

Do young hepatocellular carcinoma patients with relatively good liver function have poorer outcomes than elderly patients?

BACKGROUND AND AIM: The risk of hepatocellular carcinoma (HCC) is known to be age dependent; the influence of age on prognosis is, however, controversial. The aim of this study was to compare the tumor characteristics and survival rates of young and old HCC patients, with respect to tumor stage. METHODS: We reviewed the clinical data and survival times of 71 young HCC patients from 1987 to 2003 and compared these with those of their older counterparts (n = 239). Patients were categorized into three age groups: group A, age <30 years (n = 71); group B, age >/=30 to <61 years (n = 168); and group C, age >/=61 years (n = 81). Kaplan-Meier methods and Cox proportional hazards regression were used to analyze survival. RESULTS: The overall survival time of group A was shorter than groups B or C (P = 0.0071). Survival was not different in the three groups in subgroup analysis according to several tumor staging systems (e.g. Japan Integrated Staging score, Cancer of the Liver Italian Program scoring system and Barcelona Clinic Liver Cancer staging classification). The multivariate hazard ratio of group B was 0.840 (95% confidence interval [CI] 0.490-1.440) and that of group C was 0.770 (95% CI 0.410-1.446) in reference to group A. CONCLUSIONS: Young HCC patients showed a poorer prognosis than older HCC patients because they have a more advanced tumor stage at diagnosis. However, age was not an independent prognostic factor when stages were matched. Therefore, we suggest that periodic surveillance in young chronic hepatitis B virus carriers would improve outcomes.     

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.     

肝移植治疗原发性肝癌

目的评价原位肝移植治疗原发性肝癌的疗效和受体选择,探讨原位肝移植在原发性肝癌治疗中的作用和地位.方法回顾性分析1999年1月至2005年2月完成的9 2例原发性肝癌肝移植患者的临床资料.结果原发性肝癌肝移植92例,根据国际抗癌协会的国际癌症病期分类（TNM）,Ⅰ期8例,ChildPugh均为A级;Ⅱ期13例,Child-Pugh A级11例、B级2例;Ⅲ期12例,Child-Pugh A级8例、B级3例、C级1例;Ⅳ期59例,Child-Pugh A级52例、B级5例、C级2例.手术成功75例,成功率81.5%,围手术期死亡17例,病死率18.5%.随访6～68个月,最短生存40 d,最长无瘤生存68个月,肿瘤最短51 d复发,生存时间3年以上的7例患者至今仍无瘤生存.Ⅰ期：1年生存者5例,2年生存者3例,3年生存者2例,5年生存者1例;Ⅱ期：1年生存者6例,2年生存者2例,3年生存者2例;Ⅲ期：1年生存者3例,无生存超过2年者;Ⅳ期：1年生存者18例,2年生存者5例,3年生存者3例,5年生存者1例.Ⅰ、Ⅱ期的生存率显著高于Ⅲ、Ⅳ期.术后出现原发性肝癌复发35例,总复发率为46.7%.Ⅰ、Ⅱ、Ⅲ、Ⅳ期的复发率分别为12.5%、0、50.0%和47.5%,Ⅲ、Ⅳ期的复发率明显高于Ⅰ、Ⅱ期.结论不同期原发性肝癌肝移植术后的生存情况差别较大,肝移植治疗早期原发性肝癌效果显著,进展期原发性肝癌由于移植效果差应持慎重态度.     

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.     

Poorer prognosis in young patients with gastric cancer?

BACKGROUND/AIMS: Although the relationship between prognosis and age of patients with gastric cancer is controversial, a poorer prognosis in young patients has been suggested by most investigators. To further examine the hypothesis, a retrospective study was undertaken to analyze a large series of patients with gastric cancer in Taiwan. METHODOLOGY: A total of 1,642 consecutive patients diagnosed with gastric cancer and receiving further management at one medical center from 1988 to 1993 were reviewed. The gender, TNM tumor stage, rate of curative resection and survival of the patients were compared in the young age group (< or = 39 years) and the old age group (> 39 years). Survival was estimated with the product-limit method and difference in survival was tested by the log-rank test. Multivariate analysis was done by the Cox proportional hazard model. RESULTS: Among the 1,642 patients, 61 patients were in the young age group and 1,581 patients were in the old age group. There was no significant difference for the 2 groups of patients in the distribution of TNM stage (stage I: 20%; II: 8%; III: 13%; IV: 59% vs. 19%, 11%, 25% and 45% respectively, in the old age group, p = 0.098) and rate of curative resection (38% vs 51% in the old age group, p = 0.059). The overall 5-year survival showed no significant difference between the 2 groups (25% vs. 29% in the old). Subgroup analyses showed that survival after curative resection and survival without curative treatment (including palliative resection and no resection) also had no difference in the 2 groups. Multivariate analysis also showed that age was not an independent factor. CONCLUSIONS: Although most reports suggested a dismal prognosis in young patients with gastric cancer, based on our findings, young patients (< or = 39 years) do not have a worse prognosis than older patients.     

A new classification for hepatocellular carcinoma with portal vein tumor thrombus

Background/purpose

We aimed to correlate the survival of patients with hepatocellular carcinoma (HCC) with macroscopic portal vein tumor thrombus (PVTT) who underwent partial hepatectomy with or without portal thrombectomy with our PVTT classification. Currently, different staging systems for HCC are widely used in clinical practice. However, they lack the refinement in giving prognosis and guiding surgical treatment once macroscopic PVTT is present.

Methods

A retrospective study was carried out, in a single tertiary center, from January 2001 to December 2004 on 441 patients who underwent partial hepatectomy with or without portal thrombectomy for HCC with macroscopic PVTT. Overall survival was examined to determine whether it was correlated with our PVTT classification, and with the TNM staging, Cancer of the Liver Italian Program (CLIP) scoring system, and the Japan Integrated Staging (JIS) scoring system.

Results

With our PVTT classification, the numbers (percentages) of patients with types I, II, III, and IV PVTT were 144 (32.7%), 189 (42.9%), 86 (19.5%), and 22 (5.0%), respectively. The corresponding 1-, 2-, and 3-year overall survival rates for types I to IV PVTT were 54.8, 33.9, and 26.7%; 36.4, 24.9, and 16.9%; 25.9, 12.9, and 3.7%; and 11.1, 0, and 0%, respectively (log-rank of the survival curves P?<?0.0001). Using the TNM system, the majority of patients were classified as stage III (n?=?379 or 85.9%). Similarly, the majority of patients (n?=?388 or 88.0%) were classified as having CLIP scores of 2 (n?=?143, or 32.4%), 3 (n?=?171, or 38.8%), and 4 (n?=?74, or 16.8%). The 1-, 2-, and 3-year overall survivals for these 3 CLIP scores were very similar. Using the JIS score, the majority of patients (n?=?372 or 84.4%) were classified with a JIS score of 2. The 1-, 2-, and 3-year overall survivals of patients with a JIS score of 2 were worse than those of the patients with a JIS score of 1 (this was expected) as well as being worse than those with a JIS score of 3 (this was unexpected). Thus, the latter 3 systems of classification were not refined enough, and they were inadequate for stratifying HCC with macroscopic PVTT treated with partial hepatectomy with or without thrombectomy.

Conclusions

In patients with HCC with macroscopic PVTT treated by partial hepatectomy with or without thrombectomy, our PVTT classification better stratified and predicted prognosis than the TNM staging, CLIP scoring system, and JIS scoring system, which were unrefined and inadequate for this group of patients.     

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.     

Osteopontin,a single marker for predicting the prognosis of patients with tumor‐node‐metastasis stage I hepatocellular carcinoma after surgical resection

Background and Aim: Osteopontin (OPN) has been linked to clinical outcomes in several solid tumors. However, it has not been fully evaluated whether OPN could be used as a single marker for the prognosis of patients with hepatocellular carcinoma (HCC), particularly in patients of the tumor‐node‐metastasis (TNM) stage I. Methods: A total of 151 patients with HCC who underwent surgical resection were enrolled, including 112 patients of the TNM stage I. OPN expression was evaluated using immunohistochemistry in the tissue microarrays derived from these patients. Immunoreactivity was classified according to the percentage and intensity of staining: negative (?), weak (+) and strong (++). The impact of OPN expression on survival of patients was analyzed. Results: In total, 65.6% (99 of 151) of HCC tissues expressed OPN. Overall survival in patients of OPN (?) group was significantly higher than those of OPN (+) or OPN (++) group (P = 0.049 and P = 0.001). Interestingly, in patients of the TNM stage I, OPN expression was correlated with the early recurrence after surgical resection (P = 0.001). Multivariate analysis showed that OPN expression was an independent prognostic factor for overall survival and disease‐free survival in patients with the TNM stage I HCC (hazard ratio, 2.272, P = 0.014 and 1.982, P = 0.037). Conclusions: These results suggest that OPN is commonly expressed in HCC and is a useful marker for predicting the prognosis of patients with the TNM stage I HCC, contributing to determining which individual patient needs adjuvant therapy to prevent the early recurrence after surgical resection.     

Characteristics at presentation and outcome of hepatocellular carcinoma (HCC) in the elderly. A study of the Cancer of the Liver Italian Program (CLIP)

PURPOSE: To describe the characteristics at presentation and the outcome of elderly patients (> or =70 years old) with HCC, a retrospective analysis using a CLIP database was performed. PATIENTS AND METHODS: The database included 650 patients. Chi2-test, logistic and Cox model were applied. RESULTS: Baseline characteristics and stage were similarly among elderly (n=158) and non-elderly (n=492) patients. More elderly patients did not receive any local treatment (56% versus 38%, p<0.0001). Age and CLIP score were independently predictive of the odds of locoregional treatment. Prognosis was worse for elderly patients with a hazard ratio of death of 1.49 (95% CI 1.20-1.86) at multivariable analysis. The survival difference disappeared when patients were compared within each treatment group, suggesting a close link between undertreatment and shorter survival. CONCLUSION: Elderly patients with HCC have a worse prognosis compared to non-elderly ones. Such difference seems the consequence of undertreatment.     

Surgical resection of hepatocellular carcinoma in elderly cirrhotic patients.

BACKGROUND/AIMS: Both cirrhosis and old age have been reported to be risk factors for hepatic resection. This study evaluated the clinical results of hepatic resection in elderly hepatocellular carcinoma (HCC) patients with cirrhosis. METHODOLOGY: During a 5-year period, 248 patients with HCC underwent curative hepatic resection. Among them, 24 elderly patients (age: > or = 70 years) with cirrhosis (Group I), 24 patients (age: > or = 70 years) without cirrhosis (Group II), and 98 patients (age: < 70 years) with cirrhosis (Group III) were selected for the study. The clinical and pathologic parameters, including pre-operative demographic features, surgical factors, pathological factors, DNA flow-cytometric analysis of the resected specimen, and post-resection prognosis were compared among the three groups. RESULTS: Group I patients had a significantly higher incidence of small-size tumors, hepatitis C infection, concomitant esophageal varices, and minor resection with a shorter surgical margin in the resected specimen. The surgical morbidity and mortality of Group I was similar to that of Group II and III patients. However, the disease-free survival rate was significantly lower in the Group I patients than in Group II (p = 0.02) and Group III patients (p = 0.04). CONCLUSIONS: Our findings indicate that although hepatic resection can be done safely in elderly cirrhotic HCC patients, the prognosis for these patients was less favorable even when curative resection was performed.     

CLIP score as a prognostic indicator for hepatocellular carcinoma: experience with patients in the Middle East

OBJECTIVE: To assess the prognostic ability of the Cancer of the Liver Italian Programme (CLIP) score and compare it with the Okuda system in patients with hepatocellular carcinoma from the Middle East, where the majority (70%) present with intermediate or advanced stages of the disease and do not receive any tumour-specific treatment. METHODS: The medical records of 145 patients (113 males; mean age, 58.8 +/- 12.2 years) diagnosed with hepatocellular carcinoma over a 6-year period were reviewed and the disease was staged according to the CLIP and Okuda systems. The survival was compared by Kaplan-Meier curves and Cox regression analysis. RESULTS: The overall median survival of patients with hepatocellular carcinoma was 8.3 months (95% confidence interval, 6.6-9.4). The median survivals for CLIP score 0, 1, 2, 3 and 4-6 were 35, 29, 9, 6, and 2 months, respectively; for Okuda stages I, II and III, they were 24, 9 and 4 months, respectively. The CLIP system was judged to be statistically more efficient and consistent than the Okuda in predicting survival in the Cox proportional hazard model. CONCLUSIONS: These data from patients with hepatocellular carcinoma in the Middle East suggest that the CLIP score is more reliable than the Okuda system in predicting survival and can be used efficiently to determine prognosis in patients who present with intermediate or late stage of the disease.     

Antiviral efficacy of lamivudine versus entecavir in patients with hepatitis B virus-related advanced hepatocellular carcinoma

Background and Aim: Little information is available about the antiviral efficacy of lamivudine (LAM) and entecavir (ETV) in patients with hepatitis B virus (HBV)‐related advanced hepatocellular carcinoma (HCC). Thus, we compared the antiviral efficacy of LAM and ETV in these patients. Methods: The medical records of 134 antiviral therapy‐naïve patients with HBV‐related advanced HCC (modified Union for International Cancer Control [UICC] Tumor, Nodes, and Metastases [TNM] stages III–IV) treated between January 2005 and September 2009 were reviewed. After HCC diagnosis, 87 (64.9%) and 47 (35.1%) patients received LAM and ETV, respectively. Results: The mean age of patients (115 men, 19 women) was 53 years. Sixty‐five (48.5%) and 69 (51.5%) patients had TNM stages III and IV HCC, respectively. Treatment outcomes during follow‐up, including virologic, biochemical, and serologic responses and appearance of antiviral resistance, were similar in the LAM and ETV groups (all P > 0.05). Multivariate analysis identified Child–Pugh class, α‐fetoprotein, and TNM stage as independent predictors of overall survival (all P < 0.05). Antiviral agent type (LAM vs ETV) did not influence overall survival (median 9.6 months in LAM vs 13.6 months in ETV group; P = 0.493). HCC treatment was not interrupted due to HBV flare up in any patient. Conclusions: The antiviral efficacy of LAM and ETV was similar and the type of antiviral agent did not influence overall survival in patients with HBV‐related advanced HCC. Thus, LAM, which is less expensive than ETV in Korea, might be sufficient to control HBV in these patients.     

Prospective validation of the Chinese University Prognostic Index and comparison with other staging systems for hepatocellular carcinoma in an Asian population

Background and Aim: Hepatitis B viral (HBV) infection is the predominant etiology of hepatocellular carcinoma (HCC) in Asia. Our group previously reported a staging system known as the Chinese University Prognostic Index (CUPI) for HCC populations of which HBV infection is the predominant etiology. This study aims to validate CUPI and compare with other published staging systems. Methods: We analyzed a prospective cohort of patients with newly diagnosed HCC from 2003 to 2005. All patients were staged with CUPI, Barcelona Clinic Liver Cancer Classification (BCLC), Cancer of the Liver Italian Program score (CLIP), tumor‐node‐metastasis (TNM) and Okuda systems at diagnosis. They were followed with survival data and the performance of each staging system (in terms of homogeneity, discriminatory ability and monotonicity of gradient) were analyzed and compared. Results: A total of 595 patients (80.2% with chronic HBV infection) were analyzed. The median follow‐up was 41.4 months and the median survival was 6.6 months. Multivariate analyses identified symptomatic disease, ascites, vascular involvement, Child‐Pugh‐stage, alpha‐fetoprotein and treatment to be the independent prognostic factors. CUPI could identify three groups with statistically significant survival difference (P < 0.0001). Both CUPI and CLIP had the most favorable performance in terms of discriminatory ability, homogeneity and monotonicity. CUPI performed the best in predicting 3‐month survival while CLIP performed better in predicting the outcome of 6‐ and 12‐month survival rate. BCLC was inferior to CLIP and CUPI in the overall performance. Conclusion: We have validated CUPI in a population composed of predominant HBV‐related HCC. CUPI is an appropriate staging system for HBV‐related HCC. In patients with advanced HCC, both CUPI and CLIP offer good risk stratification.