Journal of Liver Cancer

Volume 8(1); June 2008

Review Articles

Hepatocellular Carcinoma Invading Bile Duct: Geum Youn Gwak; Journal of the Korean Liver Cancer Study Group. 2008;8(1):1-7. Published online June 30, 2008

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Abstract PDF: Although invasion of portal veins and hepatic veins is common in hepatocellular carcinoma (HCC), macroscopic bile duct invasion is rare. Bile duct thrombi have been identified in 0.5% to 9% of HCC patients. In general, these patients have a worse clinical course and shorter survival than patients without bile duct thrombi, probably attributable to the low resectability rate secondary to poor functional reserve caused by obstructive jaundice and cholangitis, and combined major vascular invasion. However, a few data demonstrated that an aggressive operative approach after appropriate preoperative management offered a better chance of long-term survival in some patients with HCC with bile duct thrombi. Herein, we describe some cases of HCC with bile duct thrombi and summarize clinical features and treatment outcomes on the basis of the literatures published to date.

Current Experience of Metastasectomy of HCC - When and for Whom?: Sang Jae Park; Journal of the Korean Liver Cancer Study Group. 2008;8(1):8-11. Published online June 30, 2008

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Abstract PDF: Intrahepatic (IH) metastasis is more frequent but extrahepatic (EH) metastasis results in worse prognosis and proper treatment on IH and EH metastasis is essential for improving the long-term survival. The purpose of this report is to review the current experience of EH metastasectomy and also to review the results of re-hepatectomy on IH metastasis after hepatectomy of HCC. EH metastasis can occur in lung, lymph nodes, bone, adrenal gland and brain in frequency. Indications of EH metastatectomy of HCC are 1) cured or controlled IH lesion, 2) acceptable operation risk, 3) complete removal of EH lesions seems possible. After lung metastasectomy, 5-year survival rates in previous reports are 23-67% according to the indications. The poor prognosis factors after lung metastasectomy are short disease-free interval between hepatectomy and lung resection, high alpha-fetoprotein. In selected patients with EH metastasis of HCC, long-term survival can be achieved by proper and aggressive surgery. The 5-year recurrence rate after hepatectomy of HCC ranges 60-100% and more than half of them is IH recurrence. IH recurrence can be classified to IH metastasis and multicentric occurrence (MO) by mode of recurrence, and MO is known to be related to HCV infection, long disease-free interval and better survival. Though it is impossible to discriminate IH metastasis and MO, re-hepatectomy should be considered in patients with single nodule recurrence and with more than 1-year of disease-free survival after hepatectomy of HCC.

Clinical Experience of Tomotherapy in Oligometastasis and Metastatic Hepatocellular Carcinoma: Chul Seung Kay, Jee Yoon Kim, Jeong Won Jang; Journal of the Korean Liver Cancer Study Group. 2008;8(1):12-15. Published online June 30, 2008

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Abstract PDF: Extracranialoligometastasis is most common in lung, liver and bone. The standard treatment is systemic chemotherapy but the value of chemotherapy is limited. So, we can suppose the beneficial effects from the addition of local therapy such as metastasectomy, cooling or heating method of tumor and radiotherapy. Stereotactic body radiotherapy is an alternative approach for surgically unresectable lesions because of proximity to blood vessels or other critical structures and multilobar involvement and for the medically inoperable patients or patients who do not require surgery. Extrahepatic metastasis from hepatocellular carcinoma has no general agreement on the optimal treatment strategy. Helical tomotherapy, a new type of dynamic radiotherapy, is an intensity modulated radiotherapy system equipped with megavoltage computed tomography image guidance. We can precisely deliver high dose of radiation to the tumor with maximal sparing of around normal tissue and simultaneously irradiate the multiple tumor using tomotherapy. We introduce the clinical experience of tomotherapy in oligometastasis and metastatic hepatocellular carcinoma for the last several years.

New Targeted Agents for Hepatocellular Carcinoma: Joong-Won Park; Journal of the Korean Liver Cancer Study Group. 2008;8(1):16-17. Published online June 30, 2008

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Abstract PDF: Most patients with hepatocellular carcinoma (HCC) present with advanced stage tumors at the time of initial diagnosis, only about 30%, who present with early stage tumors, undergo radical therapies such as resection, liver transplantation, and percutaneous ablation. Thus, over 50% of HCC patients receive palliative treatments. The newly developed, molecularly targeted agents, sorafenib is the first agent that has shown significant survival benefits for European and American patients with advanced HCC and sets the new standard for the first-line treatment of these patients. The role of sorafenib and other promising agents should be examined in the adjuvant setting after RFA, TACE, surgical resection or selective settings in liver transplantation in an attempt to improve further the outcomes of these patients.

Review of Currently Used Staging Systems for Hepatocellular Carcinoma: Jeong Won Jang; Journal of the Korean Liver Cancer Study Group. 2008;8(1):18-23. Published online June 30, 2008

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Abstract PDF: Although a number of systems have been proposed to predict the prognosis for hepatocellular carcinoma (HCC) over the past 20 years, there is no general acceptance on which of these is the most useful and reliable. The reason for this is that HCC population is heterogeneous in hepatic reserve even in the same tumor stage, and the patient survival is indeed affected by a number of factors such as underlying liver function, performance status, treatment efficacy, as well as the extent of tumor burden. In this paper, several current staging models taking into account tumor and other clinical parameters are overviewed, and their characteristics and clinical applicability for HCC patients are discussed.

Comparative Analysis of the Variable Prognostic Staging Systems for Hepatocellular Carcinoma: Sang Hoon Park; Journal of the Korean Liver Cancer Study Group. 2008;8(1):24-27. Published online June 30, 2008

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Abstract PDF: There are several worldwide prognostic staging systems for hepatocellular carinoma (HCC) since Okuda staging system was proposed in 1985. However, there is no consensus which staging system is best in predicting the survival of patients with HCC. In this review, the author investigated the value and the usefulness of known prognostic systems using the literatures. Comparative analysis was taken with focused on 1) the status of validation (internal and/or external validation), 2) the homogeneity within classification groups (treatment, survival), 3) the adequacy of study design (prospective or retrospective, single center or multi-center, and number of patients), 4) the adequacy of statistical method and 5) the concordance of between predicted and observed outcomes between all staging systems. In overall, the CLIP, BCLC and JIS staging systems provided the good stratification of patients with HCC. Although these scoring system have been well validated by many authors, they have some problems and limitations when applied to individual HCC patients, We should try to find more simple and better discriminatory prognostic scoring systems in the future

Studies for Stage and Prognosis of Hepatocellular Carcinoma in Korea: Sang Young Han; Journal of the Korean Liver Cancer Study Group. 2008;8(1):28-31. Published online June 30, 2008

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Abstract PDF: Hepatocellular carcinoma is the fifth most common cancer in the world, and the 3rd leading cause of cancer-related death. The precise stage system of hepatocellular carcinoma, which classifies patients to the same prognosis group, is important, so that it can help to choose proper treatment strategy. Staging systems used for hepatocellular carcinoma are Okuda, TNM, CLIP, French, CUPI, JIS score and BCLC classification, these staging systems have limitations in predicting patient prognosis, because these do not include tumor morphology, characteristics, clinical variables and treatment modalities properly. The staging system of hepatocellular carcinoma is still insignificantly studied in domestic. A large scale cohort study is needed including multivariables.

Hepatic Resection Following Adjuvant Treatments in Hepatocellular Carcinoma: Sae-Byeol Choi, Kyung Sik Kim; Journal of the Korean Liver Cancer Study Group. 2008;8(1):32-38. Published online June 30, 2008

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Abstract PDF: The optimal treatment of hepatocellular carcinoma has become increasingly complex with myriad of available treatment options. Although recently the liver transplantation has been accepted the best treatment for survival, the shortage of donor limits the extension of this procedures. As the neoadjuvant chemotherapy is being increasingly employed to downsize colorectal metastasis, the clinical trials have been extended to the hepatocellular carcinoma. Therefore we reviewed the use of liver resection following tumor downstaging with chemotherapeutic agents and Radiation therapy to treat unresectable HCC. Key Words: Hepatic resection․Downstaging․Transarterial chemoembolization․Radiation

Multistep Carcinogenesis of Hepatocellular Carcinoma: Ja-June Jang; Journal of the Korean Liver Cancer Study Group. 2008;8(1):39-46. Published online June 30, 2008

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Abstract PDF: Epidemiological and experimental data have demonstrated that the process of carcinogenesis is progressive and multistage in nature. Model systems in animals exhibit this property of cancer development for several organ systems. The rat liver is one of the most extensively studied models of carcinogenesis. Multiple formats have been described for the analysis of cancer development in this organ, including the resistant hepatocyte selection regimens, the neonatal rat model and the partial hepatectomy model. The evolution of hepatic neoplasia is a slow process leading from the normal state via preneoplasia to benign and malignant neoplasia. On the histological level, hepatic preneoplasia usually emerges as foci of altered hepatocytes (FAH) which are perfectly integrated in the normal liver parenchyma and have no obvious neoplastic nature. The early emergence of FAH seems to be a general phenomenon of hepatocarcinogenesis in all species, no matter how this process has been elicited. The hallmark for the definition and detection of hepatic preneoplasia are biochemical and morphological changes in the hepatocellular phenotypes, which are neither uniform nor stable. In rodent liver treated with various chemical carcinogens, most of phenotypes have been shown to represent successive stages in an ordered sequence of cellular changes, progressing from glycogenic, clear and eosinophilic cell foci, through intermediate, mixed and basophilic cell populations, to hepatocellular adenomas and carcinomas, the fast growing variants of which consist of glycogen-poor, basophilic (ribosome-rich) cells. The identification of the placental isozyme of glutathione S-transferase (GST-P) as a highly expressed cytoplasmic protein during early carcinogenesis has led to its use as a marker of hepatic tumor development in early focal lesions, nodules and carcinomas. Different lesions have been suggested to represent preneoplastic conditions in human liver. They include large-cell change, small-cell change, foci of altered hepatocytes and dysplastic nodules. Experimental results suggest that multiple progressive factors are also involved in human hepatocarcinogenesis.

Case Reports

A Case of Hepatocellular Carcinoma With Bile Duct Thrombi Presenting Obstructive Jaundice: Su Rin Shin, Geum-Youn Gwak, Cheol Keun Park, Won Jae Lee, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Won Paik, Byung Chul Yoo; Journal of the Korean Liver Cancer Study Group. 2008;8(1):47-50. Published online June 30, 2008

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Abstract PDF: Although invasion into blood vessels, particularly the portal vein, is a common feature of hepatocellular carcinoma (HCC), intrabile duct invasion has been considered rare. HCC with bile duct thrombi is occasionally misdiagnosed as biliary carcinoma or stone, and tends to have a worse clinical course than HCC without bile duct thrombi, probably attributable to the low resectability rate secondary to poor functional reserve caused by obstructive jaundice, and combined major vascular invasion. However, a few data demonstrated that obstructive jaundice aroused an early detection of HCC, leading to a better survival. Herein, we describe a case of HCC with bile duct thrombi, which was diagnosed at an early stage with obstructive jaundice and had a favorable course after surgical resection.

Extrahepatic Bile Duct Hepatocellular Carcinoma Presenting as Obstructive Jaundice: Ju Hyun Shim, Joong-Won Park, Sung-Sik Han, Joon-Il Choi, Seong Hoon Kim, Sang Jae Park, Eun Kyung Hong, Chang-Min Kim; Journal of the Korean Liver Cancer Study Group. 2008;8(1):51-54. Published online June 30, 2008

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Abstract PDF: Obstructive jaundice is a rare initial symptom of hepatocellular carcinoma (HCC) patients. We herein report a patient with extrahepatic bile duct HCC mimicking common bile duct (CBD) cancer. A 55-year-old woman with no risk factors developed jaundice of the obstructive type. On dynamic computed tomography, a low attenuated mass located in the lumen of CBD with the invasion of right posterior hepatic parenchyma was identified. After percutaneous transhepatic biliary drainage, we performed hepatectomy. Pathologic examination of the lesion confirmed the diagnosis of hepatocellular carcinoma with biliary cell differentiation extended in the CBD.

A Case of Hepatocellular Carcinoma with Bile Duct Invasion: Danbi Lee, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Young-Hwa Chung, Yung Sang Lee, Dong Jin Suh; Journal of the Korean Liver Cancer Study Group. 2008;8(1):55-58. Published online June 30, 2008

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Abstract PDF: Bile duct invasion of hepatocellular carcinoma (HCC) is rare, ranging from 1.2% to 9 %. A 51-year-old male patient visited our hospital due to jaundice. He had been infected with hepatitis B virus. He had icteric sclera without abdominal distension or tenderness. The level of total and direct bilirubin was 16.7 and 7.8 mg/dL, each other. The level of AFP was 4690 ng/mL. CT scan showed ill-defined hypervascular mass involving left hepatic lobe, left intrahepatic duct and common hepatic duct. He had been diagnosed as HCC on liver biopsy. We performed total 3 PTBDs in right, left lateral, and left medial side of the bile duct. After then, he was treated with two transarterial chemoembolizations. Finally, we carried out extended left lobectomy. After the surgery, he has been taken care at OPD without evidence of recurrence during 8 months.

A Case of Hepatocellular Carcinoma with Invasion to Bile Duct: Hyun Seok Cho, Joo Hyun Sohn, Tae Jun Byun, Sang Bong Ahn, Tae Yeob Kim, Chang Soo Eun, Yong Cheol Jeon, Dong Soo Han; Journal of the Korean Liver Cancer Study Group. 2008;8(1):59-63. Published online June 30, 2008

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Abstract PDF: A 59-year-old male patient with chronic hepatitis B and liver cirrhosis was admitted due to fever and right upper quadrant (RUQ) pain. Two years ago, he had been diagnosed with hepatocellular carcinoma with bile duct invasion and underwent left lateral segmentectomy of liver and cholecystectomy. One year after, hepatocellular carcinoma recurred in the 4th and 5th segments and transarterial chemoembolization was done for them 3 times at 2 or 3 month intervals. On this visit, he complained of general weakness, RUQ pain, fever, and weight loss. Total bilirubin was 3.1 mg/dL, ALT/AST was 81/109 IU/L, and AFP was 2.14 ng/mL. Abdomen computed tomography showed diffuse dilatation of both intrahepatic bile ducts and several small low density lesions with rim enhancement in the 4th and 8th segments. Cholangitis with liver abscesses was suspected and treatment with antibiotics started. ERCP showed narrowing of proximal and hilar portions of common bile duct and irregular shaped filling defects in the right anterior, posterior and left medial portion of intrahepatic ducts, which were believed as tumor thrombi. Despite of endoscopic retrograde biliary drainage, he died of aggravated biliary sepsis and hepatic failure.

Poorly Differentiated Hepatocellular Carcinoma with Intraluminal Metastasis to the Bile Duct: Jae Gil Lee, Yong Il Kim, Soon Hee Sung; Journal of the Korean Liver Cancer Study Group. 2008;8(1):64-68. Published online June 30, 2008

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Abstract PDF: Stem cells of the liver are differentiated to both hepatocytes and cholangiole. So bidirectional malignant transformation may be occurred. Hepatocellular carcinoma with bile-duct tumor thrombi is clinically rare and cause the obstructive jaundice. We experienced the poorly differentiated hepatocellular carcinoma showed the bidirectional differentiation. And she had metastatic foci in right intrahepatic duct with tumor thrombi to the common bile duct. A 72-year-old female patient was admitted to hospital by pruritus, general weakness and dark urine for 15 days. She was diagnosed liver cirrhosis due to chronic HBV 15 years ago. She showed icteric sclerae. The laboratory findings were followed; total bilirubin/direct bilirubin was 9.7/7.3 mg/dL, SGOT/SGPT was 59/115 IU/L, alkaline phosphatase 681 IU/L, alpha-fetoprotein was 16.9 ng/mL and CA19-9 was 76.2 U/mL. ICG-R15 was 11.8%. The hilar cholangiocarcinoma type IIIa with liver abscess was diagnosed by CT scan and MRI scan. She underwent Rt. hepatectomy with resection of CBD, Roux-en-Y hepaticojejunostomy. After pathologic examination, the poorly differentiated hepatacellular carcinoma with bile duct metastasis was confirmed. Metastasis to right lower lung was detected at 1 years after 1st operation. So, she underwent wedge resection of RLL. She remains without any problems 6 months after 2nd operation.

A Case of Hepatocellular Carcinoma with Bile Duct Invasion: Yeon Seok Seo, Beom Jin Park, Yun Hwan Kim, Soon Ho Um; Journal of the Korean Liver Cancer Study Group. 2008;8(1):69-73. Published online June 30, 2008

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Abstract PDF: Cholestatic type hepatocellular carcinoma (HCC), in which obstructive jaundice is presented as the initial presentation of HCC, is rare. The prognosis of cholestatic type HCC is generally poor and most of the patients die from cholangitis or sepsis. Although some authors reported cases of successfully treated cholestatic type HCC with surgical resection, most of the patients are inoperable at the time of diagnosis. Several reports suggested that transarterial chemoembolization (TACE) showed a beneficial effect in improving the survival time and therefore, TACE should be tried as a first choice of therapy in patients with cholestatic HCC with sufficient liver reserve function. We experienced a case of obstructive jaundice as the initial presentation of HCC. His obstructive jaundice showed significant improvement after several sessions of TACE.

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