Journal of Liver Cancer

Volume 12(2); September 2012

Review Articles

Management of Cirrhotic Complications in Hepatocellular Carcinoma: Portal Hypertension, Ascites, and Variceal Beeding: Young Kul Jung, Duck Joo Choi; Journal of the Korean Liver Cancer Study Group. 2012;12(2):85-87. Published online September 30, 2012

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Abstract PDF: Hepatocellular carcinoma (HCC) causes approximately one million deaths every year. Due to advanced stage at diagnosis, HCC carries a five-year survival rate of less than 5%, if diagnosed with unresectable disease. And also HCC is responsible for significant morbidity and mortality in cirrhosis. It leads to decompensation of cirrhosis and is the cause of death in up to 25% of cirrhotic patients. The purpose of this article is to provide an overview of the complexity in complication management of patients with terminal stage of HCC. The occurrence of complications in HCC patients is common, and includes portal hypertension, ascites, and variceal bleedings. Because of the limitations in the efficacy of current treatment options for terminal stage HCC, complication management is a key to preserving physical functioning and quality of life in these patients. Until now, diuretics remain the gold standard in management of ascites in cancer patients, and endoscopic treatment and vasoconstrictor are good choice for acute variceal bleedings. In several studies, sorafenib showed a potential as therapeutics for portal hypertension in patients with advanced HCC.

Transarterial Chemoembolization with Drug-Eluting Beads for Hepatocellular Carcinoma: Myeong Jun Song; Journal of the Korean Liver Cancer Study Group. 2012;12(2):88-92. Published online September 30, 2012

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Abstract PDF: Transarterial chemoembolization (TACE) has been widely used as a standard treatment for HCC patients who are not suitable candidates for curative treatments and as a bridge to liver transplantation. The rationale for TACE is that the intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, will result in a strong cytotoxic effect combined with ischemia (conventional TACE). Recently, drug-eluting beads (DC Bead®) for the transcatheter treatment of HCC have been developed to deliver higher doses of chemotherapeutic agent and to prolong contact time with the tumor. DC Bead® has the ability to actively sequester doxorubicin hydrochloride from solution and release it in a controlled and sustained fashion. Treatment with DC Bead® has been shown to substantially diminish the amount of chemotherapeutic agent that reaches the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment efficacy and safety of TACE with the drug-eluting bead for the treatment of hepatocellular carcinoma and discuss future therapeutic possibilities.

Transarterial Approach in Early Stage HCC: From Palliative Therapy to Curative Therapy: Jung Suk Oh, Ho Jong Chun; Journal of the Korean Liver Cancer Study Group. 2012;12(2):93-96. Published online September 30, 2012

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Abstract PDF: Early stage hepatocellular carcinoma (HCC) based on BCLC staging system can be curatively treated by liver transplantation, surgical resection or percutaneous ablation. However, transarterial approaches, including transarterial chemoembolization (TACE) or transarterial radioembolization (TARE), are standard of care for intermediate stage HCC and can be an alternative treatment in the patients with early stage HCC which are unresectable, unsuitable for percutaneous ablation, or not eligible for liver transplantation. Many previous TACE studies in early stage HCC revealed that the overall survival rate was competitive with those of curative therapies considering their operation risks, but recurrence-free survival rate was significantly lower than curative therapies. Moreover, the histopathologic reports about TACE in early stage HCC demonstrated that only 38% of the HCC nodules were completely necrotic after TACE and only 81% of the nodules with complete response by EASL criteria showed complete necrosis. Although there is no long-term survival data about TARE in early stage HCC, a histopathologic report about TARE showed that 73% of the HCC nodules were completely necrotic after TARE and 100% of the nodules with complete response by EASL criteria showed complete necrosis. In conclusion, TACE is now limited to be categorized into a curative therapy in early stage HCC, according to the previous data about TACE. However, new recent technologies including C-arm CT, superselective embolization technique, drug-eluting bead (DEB) may sufficiently improve the survival data of TACE to prove its curative role. Considering its RFA-comparable histopathologic tumor response, TARE may prove to be a potential curative therapeutic for early stage HCC.

Strategies for the Curative Therapy of Early Stage HCC: Resection, Is It Real First Choice?: Wan-Bae Kim; Journal of the Korean Liver Cancer Study Group. 2012;12(2):97-101. Published online September 30, 2012

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Abstract PDF: Early stage HCC has generally been defined as the “Milan criteria”: a solitary tumor ≤ 5 cm in size, or ≤ 3 tumors each ≤ 3 cm in size and no evidence of gross vascular invasion. HCC is now increasingly detected at earlier stages. In addition, both liver transplantation and percutaneous ablative therapies have emerged as effective alternatives to hepatic resection. As a result, the ideal treatment strategy for patients with early stage HCC, particularly in the setting of well-preserved hepatic function, has become increasingly controversial. In the recent studies, the survival rates for transplantation in early stage HCC patients are excellent. However, when intention-to-treat analysis is used, dropouts from the waiting list due to death or disease progression clearly diminish long-term survival results and therefore patients are unlikely to benefit from liver transplantation. In addition, salvage transplantation after HCC resection may be performed without excessive morbidity and may result in equivalent survival rates compared with primary liver transplantation. In some studies, salvage transplantation may be feasible in up to 75-80% of patients with recurrence following hepatic resection. Similarly, locoregional therapies serve to sustain patients with HCC on the waiting list until a transplantation become available. While RFA and TACE are commonly used to prevent dropout, pretransplant therapy has not been associated with improved overall survival or disease-free survival due to persistenceof viable tumor. It is important to note that, while resection is a more invasive procedure, the benefit that it holds over nonresectional therapies is the complete removal of the tumor allowing for subsequent detailed pathologic examination of both the tumor and surrounding liver parenchyma. In conclusion, in patients with well-preserved hepatic function, liver resection remains the most appropriate and effective treatment.

Strategies for the Curative Therapy of Early Stage HCC: First or SalvageTransplantation?: Nam-Joon Yi; Journal of the Korean Liver Cancer Study Group. 2012;12(2):102-108. Published online September 30, 2012

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Abstract PDF: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide, especially in Asian countriesas well as Korea, and liver transplantation (LT) has potentials to improve survival for patients with HCC. However, major hamper to LT for HCC has been graft shortage. To solve this problem, liver resection (LR) has to be rejuvenated in the general algorithm of HCC treatment in the light of salvage transplantation (ST) strategies. The LR followed by ST in case of HCC recurrence is an attractive concept in early stage HCC and cirrhosis with acceptable liver function. These challenges in technique, indications, pre-LT observation and treatments for recurred HCC, and prioritization policies of patients on the waiting list have to be precise through prospective investigations that have to include individualization of prognosis, biological variables and pathology surrogates as stratification criteria. Accepting this challenges have been part of the history of LT and will endure for the future. This article will focus on the ST after LR in terms of intention-to-analysis

Can Radiofrequency Ablation Replace Surgical Treatment of Hepatocellular Carcinoma?: Min Woo Lee; Journal of the Korean Liver Cancer Study Group. 2012;12(2):109-112. Published online September 30, 2012

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Abstract PDF: According to updated BCLC guideline, radiofrequency ablation (RFA) is now accepted as a standard treatment for hepatocellular carcinomas (HCCs) smaller than 2 cm in diameter in patients who are not considered for liver transplantation. This is because of acceptable local tumor control and survival gain of RFA for small HCCs compared to those of surgical resection. However, for RFA to be a standard treatment of small HCCs, not only expertise of operator but also optimal guiding and ablation techniques such as fusion imaging, contrast-enhanced ultrasonography, artificial ascites, and switching monopolar RFA using multiple electrodes are necessary. Since RFA and surgical resection are equally effective for very early stage HCC; tumor location (i.e., central vs. peripheral location, proximity to central bile duct) and individual condition of patients should be taken into consideration for choosing appropriate treatment. Microwave ablation, which is an emerging thermal ablation technique, is expected to play a key role in the local ablation therapy of small HCCs in the near future. However, more evidence and data is required to verify the efficacy of microwave ablation for the treatment of small HCCs.

Early Detection of HCC: What is the Best Strategy?: Do Young Kim; Journal of the Korean Liver Cancer Study Group. 2012;12(2):113-119. Published online September 30, 2012

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Abstract PDF: HCC is an appropriate cancer to apply surveillance program for early cancer detection. Currently, liver ultrasonography (US) combined with serum biomarker, alpha‐fetoprotein (AFP), measurement every 6 months is the standard method of HCC surveillance. Although US is the most widely used tool, its sensitivity in early HCC (within Milan criteria) detection during surveillance is only 63%. AFP is the representative biomarker for both HCC surveillance and diagnosis. The unsatisfactory performance of AFP as a surveillance tool requires discovery of novel biomarker or combination with other serum markers. Desgamma‐ carboxy prothrombin (DCP) and AFP‐L3 are candidate biomarkers which are complementary to AFP. AFP‐L3 is an emerging biomarker for diagnosis of HCC, but it needs to be validated as a surveillance tool. Regarding surveillance interval, 6 months or less seems to be superior to more longer interval in terms of early HCC detection and survival improvement. The strategies of HCC surveillance are different in countries according to health care system including available resources and health insurance coverage. Many studies demonstrated that rate of early cancer detection and application of curative therapies was increased, along with survival benefit, by HCC surveillance which is now the standard care, not just a recommendation. Improved ultrasound technology and biomarker discovery such as a specific microRNA are necessary to make more progress in HCC surveillance.

Nutrition and Management of Hepatic Encephalopathy: Jin-Woo Lee; Journal of the Korean Liver Cancer Study Group. 2012;12(2):120-127. Published online September 30, 2012

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Abstract PDF: It has been estimated that at least 25% of patients with liver cirrhosis experience hepatic encephalopathy during the natural history of the disease. Hepatic encephalopathy is more frequent in patients with more severe liver disease. Also, malnutrition is common in patients with liver cirrhosis, and is considered a significant prognostic factor affecting quality of life, outcome, and survival. Inadequate intake of nutrients, the hypermetabolic state, the diminished synthetic capacity of the liver and the impaired absorption of nutrients are themain reasons that disrupt the metabolic balance in cirrhosis. In the general approach to cirrhotic patients, the initial and most important step for the clinician is to recognize the extent of malnutrition. Unfortunately, the Child-Pugh-Turcotte classification and the model for end-stage liver disease (MELD) do not include an assessment of nutritional status in spite of the fact that malnutrition plays an important role in morbidity and mortality in end-stage liver failure. To date, the practice of dietary protein restriction for patients with liver cirrhosis is deeply embedded among medical practitioners and dietitians. However, the negative effects of protein restriction are clear, that is, increased protein catabolism, the release of amino acids from the muscle, and possible worsening of hepatic encephalopathy. Nutritional support with sufficient protein requirements, antioxidants, vitamins as well as probiotics may improve nutritional status, liver function, and hepatic encephalopathy in patients with liver cirrhosis.

Case Reports

A Case of Combination Therapy Using Radioembolization and Transarterial Chemoembolization with Drug-eluting Beads in Bilobar Hepatocellular Carcinomas: Hee Yeon Kim, Chung-Hwa Park, Do Seon Song, Myeong Jun Song, Jong Young Choi, Seung Kew Yoon, Si Hyun Bae, Ho Jung Chun; Journal of the Korean Liver Cancer Study Group. 2012;12(2):128-132. Published online September 30, 2012

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Abstract PDF: Bilobar multifocal hepatocellular carcinomas (HCCs) can be treated with transarterial radioembolization in a sequential lobar, or whole liver manner. However, radioembolization could result in a risk of radiation-induced liver toxicity in patients with reduced functional reserve. Here we describe a case with bilobar HCCs successfully treated with a combination therapy using radioembolization and transarterial chemoembolization with drug-eluting beads without significant side effects. A 72-year-old female with liver cirrhosis was diagnosed of hepatocellular carcinoma with bilobar involvement. The main mass in the left lobe was treated with radioembolization while the other lesion in the right lobe was treated with transarterial chemoembolization using drug-eluting beads, and the patient was tolerable. A combination of radioembolization and selective transarterial chemoem- bolization may be considered for an alternative option in patients with bilobar multifocal HCCs with decreased liver function.

A Case of Hepatocellular Carcinoma which Showed Response to Transarterial Chemoembolization with DC Bead® in the Patient who Showed No Response to Conventional Transarterial Chemoembolization: Do Seon Song, Hee Yeon Kim, Myeong Jun Song, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Ho Jong Chun; Journal of the Korean Liver Cancer Study Group. 2012;12(2):133-136. Published online September 30, 2012

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Abstract PDF: Hepatocellular carcinoma (HCC) is one of the most important cause of cancer death in South Korea. Approximately two thirds of the HCC patients are diagnosed in the unresectable stage. Conventional transarterial chemoembolization (TACE) showed survival benefit in the unresectable HCC patients, but it had some limitations, such as low response rate and systemic toxicity. Drug eluting bead has been reported low systemic toxicity and higher tumor necrosis rate. We report a case which showed response to TACE with DC bead in patient that showed no response to conventional TACE.

A Case of Hepatocellular Carcinoma in a 10 Year Old Child Treated with Yttrium Radioembolization and Transarterial Chemoembolization: Sung Won Lee, Hee Yeon Kim, Do Seon Song, Chung-Hwa Park, Myeong Jun Song, Jong Young Choi, Seung Kew Yoon, Jung Suk Oh, Ho Jong Chun, Si Hyun Bae; Journal of the Korean Liver Cancer Study Group. 2012;12(2):137-140. Published online September 30, 2012

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Abstract PDF: Hepatocellular carcinoma (HCC) in childhood is rare but is the second most common malignant liver neoplasm after hepatoblastoma in children. Surgical resectability is the foundation of curative therapy but only one third of newly diagnosed HCCs are resectable, and unresectable HCC remains largely unresponsive to systemic chemotherapy. In all reported series of HCC in children, therapeutic results are poor with overall survival less than 30%. Systemic chemotherapy is only partially effective but if preoperative downstaging can be achieved, it would result in a higher survival rate. There are scarce data regarding local ablative treatments such as transarterial chemoembolization (TACE) and therefore survival benefits are still unclear. TACE may be considered as a therapeutic alternative in cases of unresectable tumors after systemic chemotherapy or in unresectable, non-metastatic HCCs. The use of orthotopic liver transplantation in childhood HCC remains controversial. Radioembolization is a mode of treatment that aims to selectively target radiation to all liver tumors using yttrium-90 microspheres while limiting the dose to normal liver parenchyma. It may be considered as another treatment option in childhood HCC with the purpose of preoperative downstaging but further studies are required to determine the treatment benefits and safety of radioembolization treatment.

A Case of Hepatocellular Carcinoma with Tumor Thrombus in Inferior Vena Cava and Right Atrium: Hyun Jung Lee, Hyung Joon Yim, Hwan Hoon Chung, Seung Hwa Lee, Hae Rim Kim, Jong Jin Hyun, Sung Woo Jung, Ja Seol Koo, Sang Woo Lee, Jai Hyun Choi; Journal of the Korean Liver Cancer Study Group. 2012;12(2):141-145. Published online September 30, 2012

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Abstract PDF: In patients with advanced hepatocellular carcinoma (HCC), tumor thrombus in inferior vena cava (IVC) and right atrium (RA) are not uncommon findings and are usually associated with extremely poor outcome. Although aggressive surgical interventions such as extracorporeal circulation and tumor excision have been performed, the reported results were still unsatisfactory. Herein, we report the favorable result of combined treatment with radiation therapy and transarterial chemoembolization in a patient with advanced HCC with extensive tumor thrombus through the IVC into the RA. In conclusion, noninvasive combined modalities, such as transarterial chemoembolization and radiation therapy may sometimes provide effective palliation for patients with far advanced HCC with IVC/RA tumor thrombus and who are not candidates for alternative treatment options.

A Case of Progressive Superior Mesenteric Vein Thrombosis after Percutaneous Transhepatic Obliteration in Infiltrative Hepatocellular Carcinomaswith Portal Vein Thrombosis: Hee Yeon Kim, Chung-Hwa Park, Sung won Lee, Do Seon Song, Myeong Jun Song, Jong Young Choi, Seung Kew Yoon, Si Hyun Bae, Jung Suk Oh, Ho Jong Chun; Journal of the Korean Liver Cancer Study Group. 2012;12(2):146-150. Published online September 30, 2012

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Abstract PDF: Percutaneous transhepatic obliteration of gastroesophageal varices is one of the effective emergency procedure when endoscopic therapy is not indicated or has been failed. One of the major complications of this procedure is portal thrombosis. A 53-year-old male with hepatitis B virus infection was diagnosed of infiltrative hepatocellular carcinoma with right portal vein thrombosis. On the next day after being hospitalization, the patient developed variceal bleeding. With medical management, endoscopic therapy was initially attempted, however, it ended in failure. Emergency percutaneous transhepatic obliteration of bleeding gastroesophageal varices was considered as a next option. Bleeding from gastroesophageal varices was stopped after percutaneous obliateration, however, portal thrombosis was extended to splenic vein or superior mesenteric veins.

A Case of Refractory Hepatocellular Carcinoma Presented with Brain Metastasis: Eui Bae Kim, Soung Won Jeong, Jae Young Jang, Sae Hwan Lee, Sang Gyune Kim, Young Seok Kim, Hong Soo Kim, Boo Sung Kim, A ram Jang; Journal of the Korean Liver Cancer Study Group. 2012;12(2):151-154. Published online September 30, 2012

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Abstract PDF: Hepatocellular carcinoma (HCC) is the sixth most common tumor worldwide and the third leading cause of tumor mortality. The majority of tumors are diagnosed when advanced and then a 5-year survival rate of HCC is below 5%. However, recent progress in the diagnosis and treatment of HCC has made it possible for the patient to survive longer, and as a result, distant metastasis from HCC has increased and attracted more attention than before. HCC can be metastasized to all organs through blood and lymphatic channel. Of the various metastatic sites, the most common site is the lungs, followed by the lymph nodes, musculoskeletal, adrenal and omentum. Also, spleen, small bowel, large bowel and esophagus can be invloved. Brain metastasis can be occurred rarely, and then it is regarded to oncologic emergency. We report a patient who present with brain metastasis of progressing HCC despite of treatment.

A Case of Necrotizing Pancreatitis after Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: Mi Na Kim, Jung Hyun Cho, Young Eun Chon, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Chae Yoon Chon; Journal of the Korean Liver Cancer Study Group. 2012;12(2):155-159. Published online September 30, 2012

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Abstract PDF: Acute pancreatitis is a rare but severe postprocedural complication after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma with an incidence of 1.7-4%. The proposed mechanism of this complication is inadvertent embolization through collateral vessels or regurgitation of chemotherapeutic agents to the arteries of other organs. Here, we present a fatal necrotizing pancreatitis case which developed 10 days after TACE, caused by the regurgitation of the chemotherapeutic agents to the pancreas during the procedure. The patient recovered with conservative care at first, but after suffering from several times of recurrent pancreatitis, he died of peritoneal septic shock 5 months after the initial pancreatitis attack.

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