Japan Integrated Staging Score Research Articles

C-reactive protein to albumin ratio predicts survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib

We investigated the impact of C-reactive protein to albumin ratio (CAR) on predicting outcomes in 522 patients with unresectable hepatocellular carcinoma (HCC) treated with lenvatinib. We determined the optimal CAR cutoff value with time-dependent receiver operating characteristic curve analysis. Additionally, we clarified the relationship between CAR and liver function or HCC progression. Median overall survival was 20.0 (95% confidence interval (CI), 17.2–22.6) months. The optimal CAR cutoff value was determined to be 0.108. Multivariate analysis showed that high CAR (≥ 0.108) (hazard ratio (HR), 1.915; 95% CI, 1.495–2.452), Eastern Cooperative Oncology Group performance status ≥ 1 (HR, 1.429), and α-fetoprotein ≥ 400 ng/mL (HR, 1.604) were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high CAR (p < 0.001). Median progression-free survival was 7.5 (95% CI, 6.7–8.1) months. Multivariate analysis showed that age, CAR ≥ 0.108 (HR, 1.644; 95% CI, 1.324–2.043), and non-hepatitis B, non-hepatitis C etiology (HR, 0.726) were independently associated with progression-free survival. Cumulative progression-free survival differed significantly between patients with low versus high CAR (p < 0.001). CAR values were significantly higher as Japan Integrated Staging score increased (p < 0.001). In conclusion, CAR can predict outcomes in patients with unresectable HCC treated with lenvatinib.

Role of rapid arc-image-guided radiotherapy in hepatocellular carcinoma with portal vein tumor thrombosis: A study from tertiary care center in Punjab, India.

Treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is very challenging with poor outcome. In this situation, radiotherapy has become an alternative treatment modality, more precisely due to advances in radiation techniques. The goal of our study is to do analysis of these patients treated with rapid arc image-guided technology (RA-IGRT) at our institution. Thirteen patients were included in the study. As per intuition policy, patient set up, contouring, and treatment plans were generated. Radiological response assessment was done 1-month post-radiotherapy. Survival analysis curve along with Chi-square test for prognostic factors assessment was done using SPSS. With median dose of 45 Gy in 20 fractions, we were able to achieve 27.3% objective response rate with median survival of 5 months in eligible patients. One-year overall survival up to 30% can be achieved in HCC with PVTT, especially in patients with objective response to radiotherapy with Japan Integrated Staging score 2, provided it is precisely hit by RA-IGRT.

Nomogram for prediction of long-term survival with hepatocellular carcinoma based on NK cell counts

IntroductionAmong all immune cells, natural killer (NK) cells play an important role as the first line of defense against tumor. The purpose of our study is to observe whether the NK cell counts can predict the overall survival of patients with hepatocellular carcinoma (HCC). MethodsTo develop a novel model, from January 2010 to June 2015, HCC patients enrolled in Beijing Ditan hospital were divided into training and validation cohort. Cox multiple regression analysis was used to analyze the independent risk factors for 1-year, 3-year and 5-year overall survival (OS) of patients with HCC, and the nomogram was used to establish the prediction model. In addition, the decision tree was established to verify the contribution of NK cell counts to the survival of patients with HCC. ResultsThe model used in predicting overall survival of HCC included six variables (namely, NK cell counts, albumin (ALB) level, alpha-fetoprotein (AFP) level, portal vein tumor thrombus (PVTT), tumor number and treatment). The C-index of nomogram model in HCC patients predicting 1-year, 3-year and 5-year overall survival was 0.858, 0.788 and 0.782 respectively, which was higher than tumor–lymph node–metastasis (TNM) staging system, Okuda, model for end-stage liver disease (MELD), MELD-Na, the Chinese University Prognostic Index (CUPI) and Japan Integrated Staging (JIS) scores (p < 0.001). The decision tree showed the specific 5-year OS probability of HCC patients under different risk factors, and found that NK cell counts were the third in the column contribution. ConclusionsOur study emphasizes the utility of NK cell counts for exploring interactions between long-term survival of HCC patients and predictor variables.

Potential of PALBI-T score as a prognostic model for hepatocellular carcinoma in alcoholic liver disease.

Background and AimWith the control of viral hepatitis, alcoholic hepatocellular carcinoma (HCC) is becoming increasingly important in Japan. In alcoholic cirrhosis, the impact of portal hypertension is significant. Thus, it may be difficult to predict prognosis accurately with the reported prognostic scores. Here we propose the platelet‐albumin‐bilirubin tumor nodes metastasis (TNM) score (PALBI‐T score) as a prognostic model for HCC in alcoholic liver disease, and investigate its usefulness. The PALBI‐T score is an integrated score based on the TNM stage and PALBI grade including platelets, reflecting portal hypertension.MethodsThis study included 163 patients with alcoholic HCC treated at our Center from 1997 to 2018. We compared the prognostic prediction abilities of the Japan Integrated Staging (JIS) score, ALBI‐T score, and PALBI‐T score. The PALBI‐T score was calculated similarly to the JIS and ALBI‐T scores. Areas under the receiver operating characteristic curve (AUC) were calculated for predicting overall survival (OS).ResultsIn predicting the 1‐year survival, the JIS score had a larger AUC (AUC = 0.925) than the ALBI‐T score (AUC = 0.895) and PALBI‐T score (AUC = 0.891). On the other hand, there was no significant difference in predicting OS among the integrated scores. The PALBI‐T score (AUC = 0.740) had the largest AUC, and the JIS score (AUC = 0.729) and ALBI‐T score (AUC = 0.717) were not significantly different from the PALBI grade (AUC = 0.634). The PALBI grade reflected the degree of portal hypertension.ConclusionIn patients with alcoholic HCC, the Japan Integrated Staging score is useful for predicting short‐term prognosis. The PALBI‐T score, which reflects portal hypertension, appears to be a more valid prognostic score for predicting long‐term prognosis.

Relationship between presarcopenia and event occurrence in patients with primary hepatocellular carcinoma

Presarcopenia is a prognostic factor in patients with hepatocellular carcinoma (HCC). The Japan integrated staging (JIS) score is a prognostic method that combines the Child–Turcotte–Pugh classification and the tumor-node-metastasis (TNM) staging for HCC. We investigated the relationship between presarcopenia, the JIS score, and prognosis in patients with primary HCC. This retrospective study included 153 patients with primary HCC who were hospitalized from October 2011 to March 2018 at Municipal Hospital of Kofu. The skeletal muscle mass was measured using simplified psoas muscle mass index (PMI) based on CT imaging, and PMI using the volume analyzer SYNAPSE VINCENT ver3.0. We diagnosed presarcopenia based on the cut off value according to the assessment criteria for sarcopenia in liver disease defined by the Japan Society of Hepatology. Forty-three patients (28%) were diagnosed with presarcopenia. The median event-free survival was significantly worse in patients with presarcopenia than those without presarcopenia (P = 0.016). In multivariate analysis, presence of presarcopenia, JIS score ≥3, alpha-fetoprotein ≥200 ng/ml, and prothrombin induced by vitamin K absence-II ≥ 200 mAU/ml were significant prognostic factors. Among the patients with JIS scores ≥3, there was no difference in the event occurrence rate with presence of presarcopenia (P = 0.96). Among the patients with JIS scores ≤2, the median event-free-survival was significantly shorter in those with presarcopenia than those without presarcopenia (P = 0.045). Presarcopenia was an independent prognostic factor in patients with primary HCC. In patients with JIS scores ≤2, the median event-free survival was significantly shorter in those with presarcopenia compared to those without presarcopenia. In the patients with JIS scores ≥3, there was no difference in the event occurrence rates in those with and without presarcopenia.

Prognostic value of the albumin-bilirubin grade in patients with hepatocellular carcinoma and other liver diseases.

One of the most commonly used systems for grading liver function in hepatocellular carcinoma (HCC) patients is the Child-Pugh (CP) score. However, the CP scoring system is not without its shortcomings: for example, the cut-off values for the parameters are calculated arbitrarily and the assessment of ascites and hepatic encephalopathy is subjective. More recently, an alternative to traditional CP grade has emerged in the form of albumin-bilirubin (ALBI) grade. The predictive value provided for HCC patients by the ALBI grade is comparable to that of the CP grade; however, it can also surpass CP grade by greatly reducing subjectivity and further subdividing CP A patients into several different groups, thus improving the prognosis judgment and helping to inform clinicians’ optimal decision-making. The application of the ALBI grade into currently used HCC staging systems such as the Barcelona Clinic Liver Cancer (BCLC) staging system, the Cancer of the Liver Italian Program (CLIP) staging system, and the Japan Integrated Staging (JIS) score, etc., as well as newly produced systems like the ALBI-PLT grade, the ALBI and progression disease (ALBI-PD) grade and Modified Intermediate Stage of Liver Cancer (MICAN) criteria, greatly elevates prognostic power.

\u201cSarcopenia and intramuscular fat deposition are associated with poor survival in Indonesian patients with hepatocellular carcinoma: a retrospective study\u201d

BackgroundA large-scale Japanese study showed that low skeletal muscle index (SMI) and intramuscular fat (IMF) deposition are associated with hepatocellular carcinoma (HCC) survival. Here, we evaluated the effects of SMI and IMF on the survival of Indonesian HCC patients, whose characteristics differ from those of Japanese patients.MethodsSMI and mean muscle attenuation (MA) were evaluated using computed tomography images of the third lumbar vertebra (L3) in a prospective cohort of 100 Indonesian HCC patients. Clinical, laboratory and body composition data were analysed using the Kaplan–Meier method and Cox regression model to investigate which factors are associated with prognosis.ResultsOf 100 patients, 31 were diagnosed with sarcopenia (L3 SMI value ≤36.2 cm2/m2 for men and ≤ 29.6 cm2/m2 for women), and 65 had IMF deposition (MA value ≤44.4 HU for men and ≤ 39.3 HU for women). These groups had shorter median survival than the reference groups (both P < 0.0001). In multivariable analysis, sarcopenia (hazard ratio [HR], 1.921; P = 0.016), IMF deposition (HR, 3.580; P < 0.001), Barcelona Clinic Liver Cancer (BCLC) stages C and D (HR: 2.396, P < 0.01 and HR: 6.131, P < 0.01, respectively), Japan Integrated Staging (JIS) score 4 (HR: 2.067, P = 0.020), and male gender (HR: 3.211, P < 0.001) were independently associated with mortality.ConclusionSarcopenia and IMF deposition showed superior value in combination with BCLC stage and JIS score for predicting the survival of Indonesian HCC patients. Increased awareness and strategies to prevent or reverse these factors might improve patient outcomes. (Electric word counts: 249).

Utility of FIB4-T as a Prognostic Factor for Hepatocellular Carcinoma.

Background: Most integrated scores for predicting the prognosis of patients with hepatocellular carcinoma (HCC) comprise tumor progression factors and liver function variables. The FIB4 index is an indicator of hepatic fibrosis calculated on the basis of age, aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels, and platelet count, but it does not include variables directly related to liver function. We propose a new staging system, referred to as “FIB4-T,” comprising the FIB4 index as well as tumor progression factors, and examine its usefulness. Method: Subjects included 3800 cases of HCC registered in multiple research centers. We defined grades 1, 2, and 3 as a Fibrosis-4 (FIB4) index of <3.25, 3.26–6.70, and >6.70 as FIB4, respectively, and calculated the FIB4-T in the same manner in which the JIS (Japan Integrated Staging Score) scores and albumin-bilirubin tumor node metastasis (ALBI-T) were calculated. We compared the prognostic prediction ability of FIB4-T with that of the JIS score and ALBI-T. Results: Mean observation period was 37 months. The 5-year survival rates (%) of JIS score (0/1/2/3/4/5), ALBI-T (0/1/2/3/4/5) and FIB4-T (0/1/2/3/4/5) were 74/60/36/16/0, 82/66/45/22/5/0 and 88/75/65/58/32/10, respectively. Comparisons of the Akaike information criteria among JIS scores, ALBI-T, and FIB4-T indicated that stratification using the FIB4-T system was comparable to those using ALBI-T and JIS score. The risk of mortality significantly increased (1.3–2.8 times/step) with an increase in FIB4-T, and clear stratification was possible regardless of the treatment. Conclusions: FIB4-T is useful in predicting the prognosis of patients with HCC from a new perspective.

Validation of Modified ALBI Grade for More Detailed Assessment of Hepatic Function in Hepatocellular Carcinoma Patients: A Multicenter Analysis

Background/Aim: The frequency of hepatocellular carcinoma (HCC) in patients with good hepatic reserve function has been increasing in Japan along with the progression of antiviral therapies and aging of the society. We evaluated the usefulness of modified albumin-bilirubin (ALBI) grade as a tool for assessment of hepatic reserve function. Materials/Methods: We enrolled 6,649 naïve HCC patients treated from 2000 to 2017 and divided them into training (Ehime Prefecture group: E group, n = 2,357) and validation (validation group: V group, n = 4,292) cohorts. Child-Pugh classification and ALBI and modified ALBI (mALBI) grading were compared using with Japan Integrated Staging (JIS), ALBI-TNM (ALBI-T), and mALBI-T scores, which were calculated based on TNM stage and each assessment tool, retrospectively. Results: In the E group, Akaike’s Information Criterion (AIC) and c-index values for mALBI-T (13,725.2/0.744) were better as compared to those of ALBI-T (13,772.6/0.733) and JIS score (13,874.7/0.720), with similar results observed in the V group (mALBI-T: 27,727.4/0.760; ALBI-T: 27,817.8/0.750; JIS: 27,807.5/0.748). Although there were some significant differences between the groups with regard to clinical background factors (age, etiology, tumor size, tumor number, treatment modalities), for all patients the AIC and c-index values of mALBI-T (45,327.1/0.755) were also better than those of ALBI-T (45,467.7/0.744) and JIS scores (45,555.8/0.739), indicating its superior stratification ability and prognostic predictive value in patients with HCC. Conclusion: The detailed stratification ability of mALBI grade for hepatic reserve function is suitable for the recent trend of HCC patients, while mALBI-T may provide a more accurate predictive value than existing total staging scoring systems.

Comparison and validation of the prognostic value of preoperative systemic immune cells in hepatocellular carcinoma after curative hepatectomy.

In this study, we aimed to compare and validate the prognostic abilities of preoperative systemic immune cells in hepatocellular carcinoma (HCC) after curative hepatectomy. We developed two nomograms to predict the postoperative recurrence‐free survival (RFS) and overall survival (OS) after comparisons of the systemic immune cell prognostic scores. The two nomograms were constructed based on 305 patients who underwent curative hepatectomy for HCC. The predictive accuracy and discriminative ability of the nomograms were compared with six commonly used staging systems for HCC. The results were validated using bootstrap resampling and an internal validation cohort of 142 patients and an external validation cohort of 169 patients. Necroinflammatory activity in peritumoral liver tissues in the primary cohort was evaluated by hematoxylin and eosin (H&E) staining. Neutrophil, monocyte, and lymphocyte ratio (NMLR) had a higher area under the receiver operating characteristic curves (AUROC) value at both RFS (AUC = 0.603) and OS (AUC = 0.726) compared to that of other systemic immune cell prognostic scores. The independent predictors of RFS or OS, including α‐fetoprotein (AFP), tumor size, tumor number, microvascular invasion, and NMLR, were incorporated into the two nomograms. In the primary cohort, the C‐indexes of the RFS and OS nomograms were 0.705 and 0.797, respectively. The ROC analyses showed that the two nomograms had larger AUC values (0.664 for RFS and 0.821 for OS) than those of the American Joint Commission on Cancer seventh edition, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, Japan Integrated Staging Score, Okuda stage, and the Vauthey's system. These results were verified by internal and external validations. The nomogram‐predicted probability of RFS was associated with peritumoral necroinflammatory activity scores (r = 0.304, P < 0.001). The proposed nomograms had accurate prognostic prediction in patients with HCC after curative hepatectomy.

Prognostic significance of combined albumin-bilirubin and tumor-node-metastasis staging system in patients who underwent hepatic resection for hepatocellular carcinoma.

In recent years, the establishment of new staging systems for hepatocellular carcinoma (HCC) has been reported worldwide. The system combining albumin-bilirubin (ALBI) with tumor-node-metastasis stage, developed by the Liver Cancer Study Group of Japan, was called the ALBI-T score. Patient data were retrospectively collected for 357 consecutive patients who had undergone hepatic resection for HCC with curative intent between January 2004 and December 2015. The overall survival and recurrence-free survival were compared by the Kaplan-Meier method, using different staging systems: the Japan integrated staging (JIS), modified JIS, and ALBI-T. Multivariate analysis identified five poor prognostic factors (higher age, poor differentiation, the presence of microvascular invasion, the presence of intrahepatic metastasis, and blood transfusion) that influenced overall survival, and four poor prognostic factors (the presence of intrahepatic metastasis, serum α-fetoprotein level, blood transfusion, and each staging system (JIS, modified JIS, and ALBI-T score)) that influenced recurrence-free survival. Patients for each these three staging system had a significantly worse prognosis regarding recurrence-free survival, but not with overall survival. The modified JIS score showed the lowest Akaike information criteria statistic value, indicating it had the best ability to predict overall survival compared with the other staging systems. This retrospective analysis showed that, in post-hepatectomy patients with HCC, the ALBI-T score is predictive of worse recurrence-free survival, even when adjustments are made for other known predictors. However, modified JIS is better than ALBI-T in predicting overall survival.

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study.

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log(des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.

Usefulness of albumin–bilirubin grade for evaluation of prognosis of 2584 Japanese patients with hepatocellular carcinoma

The Child-Pugh classification has some non-objective factors, with chronic hepatitis indistinguishable from early liver cirrhosis in Child-Pugh A. We retrospectively evaluated the efficacy of albumin-bilirubin (ALBI) grade, which has been proposed as a new classification for hepatic function, for grading hepatocellular carcinoma (HCC) patients based on hepatic function and predicting their prognosis. From 2000 to 2014, 2584 naïve HCC [69.0 ± 9.8 years old, 1850 men, 734 female, Child-Pugh class A:B:C = 1871:558:155] were enrolled. TNM staging was determined using the classification of the Liver Cancer Study Group of Japan and ALBI grade, instead of Child-Pugh classification (ALBI with TNM score: ALBI-T score) (Table1), and is similar to the Japan Integrated Staging (JIS) score. We retrospectively compared ALBI-T and JIS scores in these patients. Of patients classified as Child-Pugh A (n = 1871), 1285 with 5 points were divided into 858 with ALBI grade 1 and 427 with grade 2, while 586 with 6 points were divided into 53 with grade 1 and 533 with grade 2. The ratio of ALBI grade 2 patients with a Child-Pugh score of 6 points (91.0%) was similar to that of those with 7 points (91.8%). Patients with a lower ALBI-T score (0-5 points) showed a better median survival time than those with a corresponding lower JIS score [137.7:83.2:53.4:27.4:5.0:1.4 vs 97.6:74.9:39.7:15.0:4.0:1.0 months]. Albumin-bilirubin grade was found to be superior for distinguishing patients with better hepatic function. ALBI-T scoring may be a better total prognostic scoring system for predicting survival of Japanese patients with HCC.

Comparison of the Predictive Values of Eight Staging Systems for Primary Liver Cancer in Prognosis of Combined Hepatocellular-cholangiocellular Carcinoma Patients after Surgery

To compare the predictive values of eight staging systems for primary liver cancer in the prognosis of combined hepatocellular-cholangiocellular carcinoma (cHCC-CC) patients after surgery. The clinical data of 54 cHCC-CC patients who underwent hepatectomy or liver transplantation from May 2005 to Augest 2013 in Chinese PLA General Hospital were collected. We evaluated the prognostic value of the Okuda staging system, Cancer of the Liver Italian Program (CLIP) score, French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system, 7th edition of tumour-node-metastasis (TNM) staging system for hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC), Japan Integrated Staging (JIS) score, and Chinese University Prognostic Index. The distribution, Kaplan-Meier method, Log-rank test, and area under a receiver operating characteristic curve were used to compare the prognosis-predicting ability of these different staging systems in 54 cHCC-CC patients after surgery. The TNM staging system for ICC and JIS score had a better distribution of cases. The 12-and 24-month survivals of the entire cohort were 65.5% and 56.3%, respectively. A Log-rank test showed that there was a significant difference existing in the cumulative survival rates of different stage patients when using TNM staging system for ICC (stage 1 vs. stage 2, P=0.012; stage 2 vs. stage 3-4, P=0.002), Okuda staging system (stage 1 vs. stage 2, P=0.025), and French staging system (stage A and stage B, P=0.045). The 12-and 24-month area under curve of TNM staging system for ICC, BCLC staging system, JIS score, and CLIP score were 0.836 and 0.847, 0.744 and 0.780, 0.723 and 0.764, and 0.710 and 0.786, respectively. The 7th edition of TNM staging system for ICC has superior prognostic value to other seven staging systems in cHCC-CC patients undergoing surgical treatment.

Prognosis of hepatocellular carcinoma: Assessment of eleven staging systems

Multiple staging systems have been proposed for hepatocellular carcinoma (HCC). However there is no consensus regarding which system provides the best prognostic accuracy. We aimed to investigate the performance of 11 currently used HCC staging systems. Between 2002 and 2013, a large prospective dataset of 3182 HCC patients were enrolled. The baseline characteristics and staging information were collected. Independent predictors of survival were identified. Homogeneity and corrected Akaike information criterion (AICc) were compared between each system. The median follow-up duration was 17months. Independent predictors of adverse outcome were serum albumin <3.5g/dl, bilirubin ⩾1mg/dl, creatinine ⩾1mg/dl, alpha-fetoprotein ⩾20ng/ml, alkaline phosphatase ⩾200IU/L, presence of ascites, multiple tumor nodules, maximal tumor size >5cm, presence of vascular invasion, presence of extrahepatic metastasis, and poor performance status (all p<0.001). Significant differences in survival were found across all stages of the 11 systems except between Hong Kong Liver Cancer stage IV and V, Japan Integrated Staging score 4 and 5, and Tokyo score 5 through 8. The Cancer of the Liver Italian Program (CLIP) score was associated with the highest homogeneity and lowest AICc value in the entire cohort. In subgroup analysis, the CLIP score was also superior in patients with hepatitis B- or hepatitis C-related HCC and in patients receiving curative or non-curative treatments. The CLIP staging system is stable and consistently the best prognostic model in all patients and in patients with different viral etiology and treatment strategy.

Evaluation of eight different clinical staging systems associated with overall survival of chinese patients with hepatocellular carcinoma.

Background:Hepatocellular carcinoma (HCC) is a common cancer in China, an area of high hepatitis B virus (HBV) infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients.Methods:This study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic.Results:The overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer (BCLC) staging systems had the best stratification ability and showed the lowest Akaike information criterion (AIC) values (2896.577), followed by tumor-node-metastasis 7th (TNM 7th) (AIC = 2899.980), TNM 6th (AIC = 2902.17), Japan integrated staging score (AIC = 2918.085), Tokyo (AIC = 2938.822), Cancer of the Liver Italian Program score (AIC = 2941.950), Chinese University Prognostic Index grade (AIC = 2962.027), and Okuda (AIC = 2979.389).Conclusions:BCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.

Clinical implication of performance status in patients with hepatocellular carcinoma complicating with cirrhosis.

Background and aims: The aims of our study were to elucidate the relationship between baseline characteristics of hepatocellular carcinoma (HCC) patients complicating with liver cirrhosis (LC) and performance status (PS) and to investigate the impact of PS on survival in patients with HCC complicating with LC.Methods: In a total of 1003 patients diagnosed with HCC complicating with LC, we divided into two groups of PS ≥1 (n=251) and PS 0 (n=752) as evaluated by using the Eastern Cooperative Oncology Group criteria at the time of HCC diagnosis. Baseline characteristics between these two groups were compared. We also performed univariate and multivariate analyses of factors contributing to overall survival (OS).Results: The median follow-up period was 1.6 years in the PS ≥1 group and 3.1 years in the PS 0 group. The 1-, 3- and 5-year OS rates after each initial therapy for HCC were 90.3%, 67.4% and 49.8%, respectively, in the PS 0 group and 73.4%, 42.0% and 17.7%, respectively, in the PS ≥1 group (P<0.001). A worse PS was significantly associated with age, gender, Child-Pugh classification, HCC stage, Japan Integrated Staging score, initial treatment option for HCC, maximum tumor size, alanine aminotransferase value, hypoalbuminemia, hyperbilirubinemia, renal insufficiency, hyponatremia, prothrombin time prolongation, platelet count and tumor marker level. In multivariate analyses, poorer PS was an independent predictor linked to OS with a hazard ratio of 1.773 (P<0.001).Conclusions: PS was closely associated with status of HCC patients with LC and could be an important predictor for these populations.

Hepatic arterial infusion chemotherapy with cisplatin before radical local treatment of early hepatocellular carcinoma (JIS score 0/1) improves survival.

It has not yet been determined whether hepatic arterial infusion (HAI) chemotherapy improves survival in patients with early hepatocellular carcinoma (HCC). We evaluated the effectiveness of HAI with high-concentration cisplatin (DDP-H) for the treatment of HCC by comparing outcomes between patients who received HAI with DDP-H before radical local treatment of early-stage HCC [Japan Integrated Staging (JIS) score 0/1] and patients who did not receive HAI chemotherapy. Survival was analyzed in 114 patients with early-stage HCC who underwent radical local treatment. The patients were divided into two groups: a HAI group (n = 79) who received DDP-H infusion into the whole liver via the proper hepatic artery, and a non-HAI group (n = 35) who did not receive HAI chemotherapy. The cumulative survival rates at 1, 3, and 5 years were 77.4%, 69.2%, and 55.3% in the non-HAI group and 97.4%, 87.0%, and 84.4% in the HAI group, respectively. Survival time prolonged significantly in the HAI group compared with the non-HAI group (log-rank test: P = 0.023; generalized Wilcoxon test: P = 0.012) Multivariate analysis using the Cox proportional hazards model identified HAI with DDP-H as the most important factor affecting survival. Whole-liver HAI with DDP-H before radical local treatment can improve the prognosis of patients with early-stage HCC.

Nationwide Study of 4741 Patients With Non-B Non-C Hepatocellular Carcinoma With Special Reference to the Therapeutic Impact

To examine the prognostic factors and outcomes after several types of treatments in patients with hepatocellular carcinoma (HCC) negative for hepatitis B surface antigen and hepatitis C antibody, so-called "non-B non-C HCC" using the data of a nationwide survey. The proportion of non-B non-C HCC is rapidly increasing in Japan. A total of 4741 patients with non-B non-C HCC, who underwent hepatic resection (HR, n = 2872), radiofrequency ablation (RFA, n = 432), and transcatheter arterial chemoembolization (TACE, n = 1437) as the initial treatment, were enrolled in this study. The exclusion criteria included extrahepatic metastases and/or Child-Pugh C. Significant prognostic variables determined by a univariate analysis were subjected to a multivariate analysis using a Cox proportional hazard regression model. The degree of liver damage in the HR group was significantly lower than that in the RFA and TACE groups. The HR and TACE groups had significantly more advanced HCC than the RFA group. The 5-year survival rates after HR, RFA, and TACE were 66%, 49%, and 32%, respectively. Stratifying the survival rates, according to the TNM stage and the Japan Integrated Staging (JIS) score, showed the HR group to have a significantly better prognosis than the RFA group in the stage II and in the JIS scores "1" and "2." The multivariate analysis showed 12 independent prognostic factors. HR offers significant prognostic advantages over TACE and RFA. The findings of this large prospective cohort study indicated that HR may be recommended, especially in patients with TNM stage II and JIS scores "1" and "2" of non-B non-C HCC.

Influence of etiology on host immunity in liver cirrhosis patients with advanced hepatocellular carcinoma receiving intra-arterial chemotherapy.

We have shown that continuous intra-arterial combination chemotherapy (IACC) might be more effective for advanced HCC (aHCC) in patients with HCV-related (C-LC) or alcoholic (A-LC) liver cirrhosis (LC) patients than in patients with HBV-related LC (B-LC). This study retrospectively assesses the difference of etiology on host immunity in LC patients with aHCC treated by IACC. Forty-seven adult LC patients with aHCC were treated by IACC between 2005 and 2008, with inoperable tumors according to CT findings. IACC (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was delivered via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system. The control group comprised 13 healthy volunteers. Twelve of the 47 patients with aHCC had B-LC, 27 had C-LC, and 8 had A-LC. In the B-LC group, 1 out of 12 patients had a Japan Integrated Staging (JIS) score of 2, 4 had a JIS score of 3, 7 had a JIS score of 4, and no patients had a JIS score of 5, while the respective numbers were 6, 9, 10 and 2 in the C-LC group, and 1, 1, 5 and 1 in the A-LC group. The response rates were 37.0%, 37.5% and 8.3% in the C-LC, A-LC and B-LC group, respectively. In the C-LC group, the percentage of Th1 cells before and after chemotherapy was significantly higher than in the control group. In the B-LC group, the percentage of Th2 cells after chemotherapy was significantly higher than that in the control group. However, there were no significant differences of Th1 and Th2 cells between the A-LC group and the control group. These results indicate that IACC was more effective for aHCC in A-LC patients with normal Th1/Th2 balance and in C-LC patients without Th2 dominance than in B-LC patients who showed Th2 dominance after chemotherapy.