Journal of Liver Cancer

Volume 9(1); June 2009

Review Articles

Prediction of Tumor Biology in Hepatocellular Carcinoma: Won Kim; Journal of the Korean Liver Cancer Study Group. 2009;9(1):1-6. Published online June 30, 2009

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Abstract PDF: Hepatocellular carcinoma (HCC) surveillance programs have led to an increase in the adoption of radical therapies. Nevertheless, HCCs often present at an advanced stage and the prognosis remains dismal even after resection due to the high rate of recurrence. The study of tumor biology is important to predict clinical outcome enabling more appropriate therapeutic decisions for HCC patients. Understanding molecular mechanisms of hepatocarcinogenesis may also lead to effective strategies in chemoprevention. However, current staging systems based on clinicopathologic factors are limited in prognostic prediction. Recently, there has been great interest in the study of gene expression profile in relation to prognosis of HCC. Global gene expression profiling may be the most appropriate technology to unravel the pathogenesis of HCC and explore its heterogeneous origin. The elucidation of tumor biology of HCC is of paramount clinical importance in the new era of molecular target therapy.

Is the treatment needed for massive hepatocellular carcinoma? Pros: Si Hyun Bae; Journal of the Korean Liver Cancer Study Group. 2009;9(1):7-12. Published online June 30, 2009

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Abstract PDF: Although advanced HCCs larger than 10 cm in diameter are still often seen, the survival benefit and safety of the treatments for patients with huge hepatocellular carcinoma is uncertain. With conservative management, median survival in patients whose huge tumor invades the main portal vein is approximately 3 months. Surgical resection is the only way to cure the disease for patients with big tumours. However, huge tumors frequently present with poor liver reserve, vascular invasion and intrahepatic dissemination, all the factors limit the resectability of huge HCC. Transcatheter arterial chemoembolization (TACE) is a main palliative treatment for unresectable HCC. For unresectable HCC larger than 10 cm in diameter, TACE is the only treatment option. Responses to transarterial chemotherapy are infrequent and there exists considerable skepticism as to the value of the therapy because it could give rise to excessive liver damage for huge HCCs. The recent study suggests that patients with HCC larger than 10 cm in diameter are not suitable candidates for TACE treatment because of a high mortality rate due to serious side effects. Whether TACE is beneficial or not for this type of patient deserves further study. Several investigators have sought to delineate potential benefits of various therapies, although the lack of consensus regarding standards of care in advanced HCC. There are only a limited number of reports to date focusing on TACE for patients with HCC larger than 10 cm in diameter. Herein, we conducted this retrospective, case– control study to elucidate the outcome of multimodal therapies based on TACE for patients with huge unresectable HCC and determine the factors that are independently associated with the survival.

Should We Treat Patients with Massive Hepatocellular Carcinoma? Cons: Han Chu Lee; Journal of the Korean Liver Cancer Study Group. 2009;9(1):13-16. Published online June 30, 2009

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Abstract PDF: Massive hepatocellular carcinoma (HCC) is defined as a tumor(s) involving 1 segment or more, with indistinct boundary in ≥50% of margins. There have been only few studies regarding the treatment response in patients with massive HCC. Therefore, in this review, the author focused on the treatment response in HCC of ≥10 cm in size. Reported survival rates after surgical resection are 61~66% at 1 year, 38~44% at 3 years, and 28~31% at 5 years. However, surgical resection is usually performed in patients with solitary tumor and good hepatic reserve function, and without gross vascular invasion. In addition, it was reported that surgical complication rate or mortality increases in tumors of ≥10 cm. Therefore, these data do not represent the outcome after surgical resection in patients with massive HCC. Transarterial chemoembolization (TACE) can induce objective response in about 65% of patients with HCC(s) of ≥10 cm according to modified EASL criteria. However, frequent intra- and extra-hepatic metastases are unavoidable and the survival rate was 43% at 1 year and 20% at 2 years. Of note, 11% of cases suffered from serious adverse effects such as renal impairment, sepsis and/or hepatic failure after TACE. Recently, sorafenib has been shown to increase patient’s survival, but the survival benefit is not still satisfactory. Other systemic chemotherapies using various combinations of cytotoxic agents usually show 10-20% of objective response, but there has been no evidence that it can prolong overall patient’s survival. There also has been no evidence that intra-arterial chemotherapy with or without implantable drug delivery system is superior to conventional chemotherapy or can prolong patient’s survival. In summary, treatment response in large HCC(s) is not still satisfactory and treatment-related adverse effects are considerable. Therefore, treatment should be performed in well-selected patients.

New Treatment Response Evaluation Criteria and Current Therapeutics for Hepatocellular Carcinoma: Hyung Joon Yim; Journal of the Korean Liver Cancer Study Group. 2009;9(1):17-23. Published online June 30, 2009

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Abstract PDF: There has been no proven effective therapy in the setting of advanced HCC (hepatocellular carcinoma) according to BCLC (Barcelona Clinic Liver Cancer). Targeted therapy opened a new era in this subset of patients. Although sorafenib showed survival benefit, objective tumor response is uncommon, while systemic chemotherapies sometimes show partial tumor response without statistically significant survival benefits. These findings suggest evaluation of treatment response should not depend on conventional treatment response evaluation criteria. Overall survival is now considered to be the most important endpoint and time to disease progression can be secondary endpoint. Time to recurrence is the primary endpoint after the curative therapy. Currently, targeted therapy in addition to known curative or palliative therapy is now under investigation for synergistic effects, and new therapeutic agents are under development. Such advancement in the treatment of HCC will certainly have a great impact on patients’ survival in the near future.

Is Hepatocellular Carinoma in Young Patients More Aggressive than Old Patients?: Jung Min Lee, Do Young Kim; Journal of the Korean Liver Cancer Study Group. 2009;9(1):24-28. Published online June 30, 2009

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Abstract PDF: In Korea, hepatocellular carcinoma (HCC) is a fourth leading malignancy with poor prognosis of 5 year survival reaching just 18.9%. The peak incidence is 6th decade and the incidence drops with decreasing age. However, young patients with HCC are not uncommonly encountered in clinical practice, and notably, even though managements with all available modalities are undertaken in these patients, the prognosis does not seem to be better. As such, many physicians feel that the behavior of HCC in young patients takes a more aggressive course than that in old patients. From this perspective, we performed a systemic review of previous literatures focusing on the question whether or not HCC in young patients is more aggressive; it was found that young patients with HCC had presentation of more advanced stage, more preserved liver function, but poor or equivocal survival rate. In the multivariate analysis, however, the poor outcome resulted not from young age, but from advanced stage, which was supported by similar or better outcome when the prognosis was compared with the same stage between young and old patients. Consequently, it could be inferred that an earlier detection of the tumor through earlier starting point of surveillance might improve the prognosis of young patients with HCC. However, a matter of cost-effectiveness should also be considered, which necessitates a further analysis on this issue.

Case Reports

A Case of Hepatocellular Carcinoma with Early Multiple Recurrences after Liver Resection: Jae Hong Ahn, Hyung Joon Yim, Seung Young Kim, Jeong Han Kim, Yeon Seok Seo, Seung Hwa Lee, Hwan Hoon Chung, Tae Jin Song, Hong Sik Lee, Sang Woo Lee, Soon Ho Um, Jai Hyun Choi, Ho Sang Ryu; Journal of the Korean Liver Cancer Study Group. 2009;9(1):29-32. Published online June 30, 2009

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Abstract PDF: Hepatic resection is a standard curative therapy for hepatocellular carcinoma (HCC) although only 10~30% of patients are indicated due to advanced stage or poor hepatic reserve. Five year survival rate after resection was reported as a mean of 55% (25~93%), but cases of early recurrence after hepatic resection had poor prognosis. As early recurrence after hepatic resection is the one of the most important factors that determines the prognosis, many investigators have been trying to determine the factors associated with early recurrence. We report a case of early multiple recurrence of HCC after curative hepatic resection probably due to microvascular invasion of tumor and too close resection margin. We would like to suggest that additional prophylactic measures need to be sought in this group of patients because these factors may influence on early recurrence.

A Case of Hepatocellular Carcinoma Presenting Early Intrahepatic Recurrence Following Hepatic Resection: Jaejun Shim, Byung-Ho Kim, Young Hwangbo, Sang Wook Lee, Young Ju Lee, Seung Hyung Ha, Jae Young Jang, Seok Ho Dong, Hyo Jong Kim, Young Woon Chang, Rin Chang, Sang Mok Lee; Journal of the Korean Liver Cancer Study Group. 2009;9(1):33-36. Published online June 30, 2009

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Abstract PDF: Long term results of hepatic resection for hepatocellular carcinoma (HCC) are not satisfactory due to a high incidence of postoperative recurrence. To improve the prognosis in patients who underwent hepatic resection, identification of risk factors for recurrence and development of effective preventive strategies are required. A single nodular mass was found in the right hepatic lobe of 53-year old male with B viral cirrhosis by surveillance ultrasonography. Dynamic abdominal CT showed a 3 cm-sized hypervascular mass in the right posteroinferior segment (S6). AFP was 359 ng/mL. Child-Pugh classification was A, and ICG R15 was 18.8%. After preoperative transarterial chemoembolization (TACE), right hepatic wedge resection was performed. Resection margin was free of tumor. Microinvasions in the surrounding vessels, lymphatics, bile ducts were not found and microsatellite nodules were absent in the resected specimen. Although there were no risk factors that associated with high postoperative recurrence, multifocal intrahepatic recurrence in the right lobe and left medial lobe occurred at 7 months after hepatic resection. He underwent two sessions of TACE.

Early Intrahepatic Recurrence of Hepatocellular Carcinoma with Metastasis to Lung and Brain after Radiofrequency Ablation: Jin Dong Kim, Jung Hyun Kwon, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Young Jun Lee, Sung Eun Rha, Ho Jong Chun, Byung Gil Choi, Hae Giu Lee; Journal of the Korean Liver Cancer Study Group. 2009;9(1):37-40. Published online June 30, 2009

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Abstract PDF: Radiofrequency ablation (RFA) is the preferred method of local ablation for patients with small (<3 cm sized) hepatocellular carcinoma (HCC) when surgical resection cannot be applied. If RFA procedure is sufficiently completed, it provides lower local tumor recurrence, and longer overall as well as disease-free survival. We experienced a case of early stage HCC which recurred at 2 months after successful RFA procedure, and rapidly metastasized to lung and brain.

A Case of Early Recurred Hepatocellular Carcinoma with Initial Expectation of Good outcome by Surgical Resection: Jung Min Lee, Jun Yong Park, Do Young Kim, Kyung Sik Kim, Young Nyun Park, Myeong-Jin Kim, Chae Yoon Chon, Kwang-Hyub Han; Journal of the Korean Liver Cancer Study Group. 2009;9(1):41-44. Published online June 30, 2009

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Abstract PDF: Hepatocellular carcinoma (HCC) is one of the cancers with poor prognosis as HCC develops on base of cirrhosis in majority cases, which requires multidisciplinary approach. If feasible, however, surgical resection is the choice of treatment, and many previous studies and guidelines offered appropriate indications for surgical resection; firstly, preservation of liver function should be confirmed with traditional Child-Pugh classification or more recently with Indocyanine Green retention test or absence of portal hypertension. Secondly, several variables about the size, number, and vascular invasion of tumor should be taken into consideration. It is suggested that to lessen the risk of recurrence gross vascular invasion be absent and the number of tumor be single. Regarding the size of tumor, although risk of dissemination increases with size, some tumors may grow as a single mass and thus the size of tumor is not a clear-cut limiting factor. Based on above suggestions, we herein offer our experience of a patient with initial hopeful expectation of good outcome with surgical resection, but who eventually turned out to result in disseminated tumor recurrence. Further study, maybe regarding a combination of adjuvant or neoadjuvant transarterial chemoembolization/chemotherapy or radiotherapy, is necessary on how to manage such patient.

Rapid recurrence following living donor liver transplantation for hepatocellular carcinoma within Milan criteria: Hyun Young Woo, Jin Dong Kim, Jung Hyun Kwon, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Sung Eun Rha, Jae Young Byun, Ho Jong Chun, Byung Gil Choi, Hae Kyu Lee, Young Kyoung You, Dong Gu Kim; Journal of the Korean Liver Cancer Study Group. 2009;9(1):45-48. Published online June 30, 2009

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Abstract PDF: Liver transplantation is curative therapy for hepatocellular carcinoma especially if ,within Milan criteria, 4 year survival and recurrence-free survival was reported to be 85% and 92%, respectively. Herein we report a patient who experience rapid recurrence following living donor liver transplantation (LDLT) for hepatocellular carcinoma within Milan criteria. A 52 year-old-men patient with known liver cirrhosis associated with hepatitis B virus was admitted for the treatment of hepatocellular carcinoma (HCC). Abdominal CT revealed two nodules less than 3 cm in right hepatic lobe. After single session of transcatheter arterial chemoembolization (TACE), the patient underwent LDLT. After seven months following transplantation, recurrent HCC was detected on transplanted liver with concurrent metastatic nodule in lung. Although TACE and metastsectomy were performed for recurrent intrahepatic mass and lung metastasis, recurrent HCC showed rapid progression and patient died of progressive tumor after 10 months following LDLT.

A Case of Hepatocelluar Carcinoma with Portal Vein Tumor Thrombus arterial: Jong Kyu Park, Young Seok Kim, Sang Gyune Kim, Seung Won Jeong, Jae Young Jang, Hyun Jong Choi, Jong Ho Moon, Hong Soo Kim, Moon Sung Lee, Chan Sup Shim, Boo Sung Kim; Journal of the Korean Liver Cancer Study Group. 2009;9(1):49-52. Published online June 30, 2009

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Abstract PDF: Recent progress in imaging techniques has permitted the diagnosis of hepatocelluar carcinoma (HCC) at an early stage. However, portal vein invasion is still found in 12.5~39.7%. HCC with tumor thrombosis of the portal vein has a poor prognosis. Previous studies showed that the median survival time of patients with HCC with involving portal vein was 2.7~4 months if effective treatment was not administered. Thus, for such HCC with portal vain invasion, an effective therapy that will maintain quality of life is required. We report a case of HCC with portal vein tumor thrombus treated by intra-arterial chemotherapy.

Treatment of Massive Hepatocellular Carcinoma with Portal Vein Invasion: Jung Hyun Kwon, Jong Young Choi, Jin Dong Kim, Hyun Young Woo, Si Hyun Bae, Seung Kew Yoon, Young Jun Lee, Ho Jong Chun; Journal of the Korean Liver Cancer Study Group. 2009;9(1):53-58. Published online June 30, 2009

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Abstract PDF: A 52 year-old-man patient was admitted for evaluation of hepatic mass which was detected on screening ultrasonography. His abdominal CT showed a massive infiltrating mass in left hepatic lobe and another 2.4 cm nodule in S6 of Rt. Hepatic lobe with arterial enhancement and rapid wash out underlying liver cirrhosis. Also, low density tumor thrombus are filled in Lt. portal vein and extended into main portal vein. He was finally diagnosed HCC (UICC stage IVa) with liver cirrhosis (Child-Pugh class A) and hepatitis B. With the four times of trasnarterial chemo-lipiodolization and seven times of intraarterial infusion chemotherapy for huge mass and one time Radiofrequency ablation (RFA) for daughter nodule, his HCC showed no stain in hepatic angiogram at nine month from initial diagnosis. After additional eight times of intra-arterial infusion chemotherapy, new small nodule developed in S6 and was ablated with RFA. At eighteen months after initial diagnosis, he shows no viable lesion on the imaging study and tumor markers are normalized.

A Case of Massive HCC Treated with Surgical Resection: Shin Young Lee, Hee Bok Chae, Dong Hee Ryu, Il Hun Bae, Rohyun Sung; Journal of the Korean Liver Cancer Study Group. 2009;9(1):59-62. Published online June 30, 2009

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Abstract PDF: A 59-year-old male patient visited ER complaining of persistent pain in his right upper quadrant abdomen. He had suffered from end stage renal disease secondary to long-term hypertension and had been under the maintenance hemodialysis for 13 years. Half a month ago, he recognized a mass at his epigastric area. He did not have any history of liver disease in his lifetime. Physical exams revealed that he had a tender and hard mass on his right upper quadrant and epigastric area. Total bilirubin was 0.6 mg/dL, AST/ALT was 59/75 IU/L, and AFP was 105,740 ng/mL. Computed tomography showed the huge liver mass in the left lobe and its size was estimated about 16cm. The regional lymph node was also found in the porta hepatis area. He received complete resection of the hepatoma and was discharged. We concerned about high probability of recurrence because of the pre-operative AFP level and vascular invasion in the pathologic specimen.

A Case of Massive Hepatocellular Carcinoma Treated by Hepatic Resection, which did not Respond to Transarterial Chemoembolization: Jeong Han Kim, Hyung Joon Yim, Seung Young Kim, Jae Hong Ahn, Ji Hoon Kim, Yeon Seok Seo, Seung Hwa Lee, Hwan Hoon Chung, Tae Jin Song, Hong Sik Lee, Sang Woo Lee, Jai Hyun Choi; Journal of the Korean Liver Cancer Study Group. 2009;9(1):63-66. Published online June 30, 2009

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Abstract PDF: Surgical resection is the treatment of choice for hepatocellular carcinoma (HCC) in non-cirrhotic patients. The optimal indication for resection is a single tumor in a suitable location for resection. However, limit of the tumor size is not clear. We report a case of successful hepatic resection in patients with massive HCC sized more than 15 cm that did not respond to transarterial chemoembolization (TACE). A 49-year-old male patient had received TACE two times for massive HCC. However, the tumor size increased. Right hemihepatectomy was performed despite the extensive tumor size and underlying liver cirrhosis. Ascites and wound infection were developed after resection, but the patient’s general condition got recovered soon. Until 6 months after surgery, recurrence has not been detected. However, distant metastasis was noted at 7th month. Although recurrence with distant metastasis was noted, we think aggressive surgical approach prolonged this patient’s survival.

A Case of Curative Resection of Advanced Hepatocellular Carcinoma After Localized Concurrent Chemo-Radiation Therapy: Jee Suk Kwon, Jeong Eun Lee, Woo Young Park, Kyung In Lee, Eun Soo Kim, Byoung Kuk Jang, Woo Jin Chung, Kyung Sik Park, Kwang Bum Cho, Jaeseok Hwang; Journal of the Korean Liver Cancer Study Group. 2009;9(1):67-70. Published online June 30, 2009

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Abstract PDF: Advanced hepatocellular carcinoma (HCC) with portal vein thrombosis is not suitable candidates for surgical treatment at the most of diagnosis because of poor liver function, extensive tumor involvement of the liver, vascular involvement, and/or intra/extrahepatic metastasis. We attempted localized concurrent chemo-radiation therapy (CCRT) in patients having locally advanced HCC with left and main portal vein thrombosis. We report a case of locally advanced HCC patient who became surgically resectable by downstaging after localized CCRT. Localized CCRT was performed with a total radiation dose of 5,040 cGy (180 cGy×28 times) and hepatic arterial infusion of 5-fluorouracil (5-FU, 250 mg/day) and cisplatin (10 mg/day) for 5 days via implantable port system during the second and the fifth weeks of the radiotherapy. Marked contraction of HCC was noted on follow up computerized tomography (CT) after localized CCRT, and subsequently surgical resection with curative aim was performed. He was gave a additional transcatheter arterial chemoembolization (TACE) because follow up CT revealed intrahepatic metastasis at subcapsular portion of right hepatic lobe after 3 months of operation. The patient is in complete remission status without recurrence to date.

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