Hiroko Oka

Validation of a New Prognostic Staging System for Hepatocellular Carcinoma: the JIS Score Compared With the CLIP Score

The Japan Integrated Staging score (JIS score), which combines the Child‐Turcotte‐Pugh classification and tumor‐node‐metastasis staging, has been proposed as a better prognostic staging system for hepatocellular carcinoma (HCC) than the Cancer of the Liver Italian Program (CLIP) scoring system. In this study, validation was performed among a larger patient population. A total of 4,525 consecutive patients with HCC who had been diagnosed at five institutions were included. Stratification ability, prognostic predictive power, and reproducibility were analyzed and compared with results from the CLIP scoring system. Only 45% (1,951 of 4,525) of all patients were categorized as early stage HCC according to JIS score (0 or 1), whereas 63% (2,878 of 4,525) of the patients were categorized as having a CLIP score of 0 or 1. Significant differences in survival curves were not observed among CLIP scores 3 to 6. In contrast, survival curves showed significant differences among all the JIS scores. The same JIS scoring subgroups showed a similar prognosis, and good internal reproducibility was observed in each of the institutions. Multivariate analysis of the prognosis in all 4,525 patients proved the JIS score to be the best prognostic factor. Furthermore, the Akaike information criteria proved that the JIS scoring system was statistically a better model for predicting outcome than the CLIP scoring system. In conclusion, the stratification ability and prognostic predictive power of the JIS score were much better than that of the CLIP score and were simple to obtain and remember. (HEPATOLOGY 2004; 40:1396–1405.)

Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive α-fetoprotein1

Background and Aim: The Lens culinaris agglutinin‐reactive fraction of α‐fetoprotein (AFP‐L3) has been reported to be a highly useful marker for hepatocellular carcinoma (HCC) compared with a conventional serum AFP concentration, which allows earlier detection of HCC compared with using other imaging modalities and predicting prognosis after therapy. A collaborative prospective study involving nine Japanese hospitals was conducted to analyze the relationships between the tumor characteristics of a HCC patient and the percentage of AFP‐L3/AFP total at the initial detection.

Prognostic value of pretreatment levels of tumor markers for hepatocellular carcinoma on survival after curative treatment of patients with HCC

BACKGROUND/AIMS We evaluated the prognostic value of the pretreatment elevation of tumor markers for hepatocellular carcinoma (HCC) in patients who underwent curative treatment. METHODS We studied 801 patients who had been diagnosed as initial HCC and fulfilled the following criteria: maximum tumor size, < or = 3 cm; number of tumors, < or = 3; remnant liver function, Child-Pugh class A or B; treated by hepatectomy or locoregional thermal ablation (LTA); and alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma carboxy prothrombin (DCP) were measured at diagnosis. We analyzed the effects of elevated tumor markers on patient survival in these 2 distinct groups with different types of treatment, i.e. hepatectomy and LTA. RESULTS By multivariate analysis in 345 patients who underwent hepatectomy, no tumor marker significantly affected decreased survival rate. In the 456 patients who underwent LTA, the elevation of AFP-L3 (p=0.0171) and DCP (p=0.0004) significantly affected decreased survival rate; DCP elevation had the strongest effect on patient survival. CONCLUSIONS The prognostic value of pretreatment tumor marker elevation was different in patients who underwent the curative treatment according to the type of treatment. Pretreatment elevation of AFP-L3 and DCP had prognostic values only in patients treated with LTA.

Severe Complications of Radiofrequency Ablation Therapy for Hepatocellular Carcinoma: An Analysis of 3,891 Ablations in 2,614 Patients

Objective: To clarify information on and frequency of complications as well as mortality rate after radiofrequency ablation (RFA) for hepatocellular carcinoma.Methods: The results of a questionnaire obtained mainly from members of the Osaka Liver Cancer Study Group at 43 departments of 38 facilities were analyzed in order to clarify the current status of RFA, and information on and frequency of complications and death occurring after RFA. Results: Between January 1999 and May 2002, a total of 3,891 RFA therapies were performed percutaneously in 2,542 patients, laparoscopically in 23, and operatively in 49 (2,614 patients in total). Complications were observed in 207 of 2,614 patients (7.9%), and 9 (0.3%) died within 3 months after RFA. Among these 9 nonsurvivors, 3 had liver failure, 3 rapid progression and sarcomatous changes, 1 biliary injury, 1 gastrointestinal bleeding, and 1 acute myocardial infarction. The departments that treated larger numbers of patients per month had a smaller number of complications and deaths. Conclusion: It is possible that complications of RFA can be reduced by gathering experience.

Effect of vitamin K2 on the recurrence of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, even after curative treatment. Vitamin K2, which has been reported to reduce HCC development, may be effective in preventing HCC recurrence. Patients who underwent curative ablation or resection of HCC were randomly assigned to receive placebo, 45 mg/day, or 90 mg/day vitamin K2 in double‐blind fashion. HCC recurrence was surveyed every 12 weeks with dynamic computed tomography/magnetic resonance imaging, with HCC‐specific tumor markers monitored every 4 weeks. The primary aim was to confirm the superiority of active drug to placebo concerning disease‐free survival (DFS), and the secondary aim was to evaluate dose‐response relationship. Disease occurrence and death from any cause were treated as events. Hazard ratios (HRs) for disease occurrence and death were calculated using a Cox proportional hazards model. Enrollment was commenced in March 2004. DFS was assessed in 548 patients, including 181 in the placebo group, 182 in the 45‐mg/day group, and 185 in the 90‐mg/day group. Disease occurrence or death was diagnosed in 58, 52, and 76 patients in the respective groups. The second interim analysis indicated that vitamin K2 did not prevent disease occurrence or death, with an HR of 1.150 (95% confidence interval: 0.843‐1.570, one‐sided; P = 0.811) between the placebo and combined active‐drug groups, and the study was discontinued in March 2007.

Validation of a new prognostic staging system for hepatocellular carcinoma: a comparison of the biomarker-combined Japan Integrated Staging Score, the conventional Japan Integrated Staging Score and the BALAD Score.

Objectives: The conventional Japan Integrated Staging (c-JIS) score has been reported to effectively stratify patients with hepatocellular carcinoma (HCC). Recently, two new staging systems, the biomarker-combined JIS (bm-JIS) score and the BALAD score, have been proposed. Both staging systems include three tumor markers: α-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP and des-γ-carboxy prothrombin specific for HCC. The aim of this study is to evaluate the performance of these three staging systems. Methods: A total of 1,173 HCC patients were included in this study. The stratification ability and prognostic predictive power were compared between these three staging systems. Results: These three staging systems effectively predicted the patient survival. When accounting for the best prognostic subgroup of each staging systems (i.e. score of 0), there were significant differences between the bm-JIS score and the BALAD score and, likewise, between the c-JIS score and the BALAD score. The likelihood ratio χ2 test showed the highest value and the Akaike information criterion value was lowest in the bm-JIS score. Conclusions: The bm-JIS score showed good stratification ability and was thus demonstrated to be a better predictor of the prognosis than the c-JIS score and the BALAD score, especially for the patients with a good prognosis.

Erythrocytosis caused by an erythropoietin-producing hepatocellular carcinoma

A case of erythrocytosis caused by a hepatocellular carcinoma (HCC) that produced erythropoietin (Epo) is described. A 64‐year‐old man, with a huge HCC tumor in the right lobe of the liver, showed a high concentration of hemoglobin and increased levels of serum Epo, α‐fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA‐II). Right lobectomy of the liver was performed. Histological findings of the specimen showed a moderately differentiated HCC. The existence of Epo was confirmed immunohistochemically only in the tumor tissue and not in the normal liver tissue. Erythrocytosis disappeared and the serum levels of Epo, AFP, and PIVKA‐II returned to the normal range after the operation. Within 2 months after the operation, recurrent tumors appeared in the remnant liver, and the patient died 13 months after the operation. J. Surg. Oncol. 2000;75:197–202.

Spontaneous Regression of Hepatocellular Carcinoma: Report of a Case

A spontaneous regression of hepatocellular carcinoma is an extremely rare phenomenon. A 69-year-old Japanese man with hepatitis C virus-related chronic hepatitis presented with a liver tumor. We diagnosed the tumor to be hepatocellular carcinoma in the course of spontaneous regression, by imaging studies and changes in the tumor markers. Because the possible presence of viable cancer cells could not be ruled out, we recommended surgery. He refused all treatments at first, but finally agreed to undergo surgery about 10 months after presentation. A hepatectomy was performed. Histologically, no viable tumor cells were found. In our case, the vascularity of the tumor according to the imaging findings was followed up during the clinical course. The patient is now doing well and without any evidence of recurrence at 37 months after surgery.

A New Prognostic Staging System for Hepatocellular Carcinoma: Value of the Biomarker Combined Japan Integrated Staging Score

Objectives: The Japan Integrated Staging (JIS) score has been reported to have good stratification ability in patients with hepatocellular carcinoma (HCC). However, the JIS score could not estimate malignant grade of HCC. The aim of this study was to evaluate the performance of a new staging system: the biomarker combined JIS (bm-JIS) which includes three tumor markers: α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP and des-γ-carboxy prothrombin with the conventional JIS score. Methods: A total of 1,924 HCC patients were included in this study. We compared their overall survival, the stratification ability and suitability as a prognostic model according to the bm-JIS score and the conventional JIS score. Results: There were significant differences between the survival curves for all bm-JIS scores. For the conventional JIS scores of 0, 1, 2 and 3, the survival curves differed greatly according to the bm-JIS score (p < 0.0001). The independent homogenizing ability and the stratification value of the JIS score and the bm-JIS score determined by the likelihood ratio test using the Cox proportional hazard regression model showed the bm-JIS score to have a higher value(χ2 = 717.348) than the JIS score (χ2 = 668.91). Conclusions: The bm-JIS score showed superior stratification ability and thus was found to be a better predictor of the prognosis than the conventional JIS score, especially for the patients with good prognosis.

Role of tumor markers in assessment of tumor progression and prediction of outcomes in patients with hepatocellular carcinoma

The efficacies of tumor markers, alfa‐fetoprotein (AFP), Lens culinaris agglutinin A‐reactive fraction of alfa‐fetoprotein (AFP‐L3), and des‐gamma‐carboxy prothrombin (DCP) were evaluated for assessment of progression of hepatocellular carcinoma (HCC) and patient prognosis. The prevalence of elevated levels of each tumor marker increased with progression of tumor stage for all three markers among patients with HCC. Survival was poorer among patients with elevated levels of tumor markers than among those without elevated levels.Evaluation of tumor progression with tumor markers was based only on the results of laboratory tests. The tests are objective, simple to perform, and easy to repeat, and therefore, may be useful to supplement conventional tumor staging for the evaluation of tumor progression and prediction of patient outcome.