Journal of Liver Cancer

Volume 11(2); September 2011

Review Articles

Toll-like Receptors and Carcinogenesis: Geum-Youn Gwak; Journal of the Korean Liver Cancer Study Group. 2011;11(2):97-103. Published online September 30, 2011

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Abstract PDF: Toll-like receptors are a family of pattern recognition receptors that allow the immune system to sense molecules that are present in most classes of pathogens such as bacteria and viruses, but not the host, and to coordinate defense mechanisms against these pathogens. Emerging evidence also suggests that TLRs have an important role in maintaining tissue homeostasis by regulating the inflammatory and tissue repair responses to injury. Due to the important role in inflammation, tissue regeneration and fibrogenesis, TLRs are potential candidates to mediate effects of the innate immune system on carcinogenesis. Although the role of TLRs in carcinogenesis is far from being completely understood, current data suggest a dual role of TLRs in carcinogenesis: anti-tumor effects versus tumor-promoting effects. Here we discuss how TLRs function in the context of carcinogenesis.

Roles of Surgical Treatment for Patients with Advanced Hepatocellular Carcinoma: Hyung Jun Kwon, Yoon Jin Hwang; Journal of the Korean Liver Cancer Study Group. 2011;11(2):104-110. Published online September 30, 2011

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Abstract PDF: Hepatic resection for Hepatocellular carcinoma (HCC) is potentally curative treatment for selected patients. However, the roles of surgical treatment for advanced hepatocellular carcinoma are still uncertain. Although aggressive surgical approach is not recommandable to all patients with advanced HCC, it is clear there is a group of patients that will benefit. In this review article, the authors would like to examine the roles of surgical treatment for patients with advanced hepatocellular carcinoma (HCC) by ascertaining the feasiability and results of surgical resection.

Response Evaluation Assessment in HCC: Modified RECIST: So Yeon Kim; Journal of the Korean Liver Cancer Study Group. 2011;11(2):111-115. Published online September 30, 2011

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Abstract PDF: The accurate evaluation of response to treatment is a key aspect in cancer therapy, because an objective response may become a surrogate marker of improver survival. For cytotoxic drugs, tumor response evaluation according to the World Health Organization (WHO) criteria or the Response Evaluation Criteria in Solid Tumors (RECIST) guideline offers simple approaches based on the size of the lesions. However, considering the nature of locoregional therapy or new cytostatic agent for hepatocellular carcinoma (HCC), which do not decrease the size of the tumor but induce tumor necrosis, original WHO or RECIST criteria will not reflect clinical benefit exactly. Recently, modified RECIST assessment is proposed by AASLD-JNCI guidelines. Given that complete necrosis was well correlated with better survival, modified RECIST criteria consider changes in tumor viability, which can be measured as the area of arterial enhancement, with maintaining overall response assessment similar to RECIST. The proposed modified RECIST assessment is expected to provide a reliable method for assessing tumor response in HCC clinical trials.

Percutaneous Intratumoral Chemo-Immunotherapy with 5-Fluorouracil and Recombinant Interferon-Gamma for Advanced Hepatocellular Carcinoma: Young Min Park; Journal of the Korean Liver Cancer Study Group. 2011;11(2):116-129. Published online September 30, 2011

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Abstract PDF: Transarterial chemo-embolization using adriamycin or cisplatin, lipiodol and gelfoam (TACE-Adr or -CDDP) has been recommended for the treatment of hepatocellular carcinoma (HCC), which are not indicated for the curative therapy, such as liver transplantation, operation, and radiofrequency ablation therapy (RFA). However, TACE-Adr/-CDDP protocol is effective only for single or few nodular HCCs with largest diameter less than 6 cm and without major vascular involvement or distant metastasis (AJCC/UICC 6th.edition-TNM-II). To treat more complicated far advanced HCCs, various multiplicinary approaches have been tried, but most studies are too preliminary and immature to be used as standard treatment protocols. In such situation, a combination protocol, called TACE-EC/F, in which TAC-Epirubicin and Cisplatin is followed by systemic intra-venous infusion of 5-fluorouracil (5-FU), has been a good option. To improve its therapeutic efficacy, I replaced its systemic 5-FU (for 5 days continuous) infusion part to the (one time) percutaneous intratumoral injection chemotherapy (PIC) with a mixture of high dose 5-FU and recombinant interferon-gamma (IFN-gamma), named PIC-IF. This protocol was developed based on both the
results
of several experimental data and many clinical experience of percutaneous ethanol injection therapy (PEIT). This TACE-EC/PIC-IF protocol showed a possibility of new multimodality approach for the treatment of advanced HCC.

The Role of TIS21/BTG2/PC3 during Hepatocarcinogenesis: Tae Jun Park; Journal of the Korean Liver Cancer Study Group. 2011;11(2):130-135. Published online September 30, 2011

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Abstract PDF: A functional and biochemical features of TIS21(/BTG2/PC3) was explored in hepatocarcinogenesis. Growth of hepatocellular carcinoma (HCC), developed by a single injection of diethylnitrosamine (DEN) was significantly higher in the TIS21 knockout mice at 9 months. Expression of BTG2/TIS21 was significantly lower in both human and mouse hepatocellular carcinoma than in the surrounding normal tissues. Over-expression of TIS21 inhibited cell proliferation and tumorigenic potential of Huh7 hepatoma cells. At the molecular mechanistic level, TIS21 inhibited FoxM1 phosphorylation, by reducing cyclin B1-cdk1 activity. Furthermore, TIS21 inhibited FoxM1 transcriptional activity. In conclusion, TIS21 negatively regulated hepatocarcinogenesis in part by disruption of the FoxM1-cyclin B1 regulatory loop, thereby inhibiting proliferation of transformed cells developed in mouse and human livers.

Changes of Hepatocellular Carcinoma Guidelines during the Last Ten-Year Period: Do Seon Song, Si Hyun Bae; Journal of the Korean Liver Cancer Study Group. 2011;11(2):136-143. Published online September 30, 2011

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Abstract PDF: Hepatocellular carcinoma (HCC) is the third most common cause of cancer death in the world. There has been many advances in diagnosis of HCC during the last ten-year period, especially imaging techniques. The Korean Liver cancer study group (KLCSG), European Association for the Study of the Liver (EASL), American Association for the Study of Liver disease (AASLD) and Asian-Pacific Association for the Study of Liver (APASL) have made and changed HCC guidelines with advances of imaging technique and results of research on HCC. We reviewed the changes of imaging guidelines in HCC diagnosis according to the advances of imaging. In addition, further studies will be needed to solve the controversies in diagnosis of HCC smaller than 1 cm in size.

Complications Associated with Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma: Sun Hong Yoo, Si Hyun Bae; Journal of the Korean Liver Cancer Study Group. 2011;11(2):144-148. Published online September 30, 2011

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Abstract PDF: Transcatheter arterial chemoembolization (TACE) is one of the most effective treatments for patients with inoperable hepatocellular carcinoma (HCC). However, variable complications can occur after TACE. Complications resulting from TACE contain postembolization syndrome, liver abscess, bile duct injury, ruptured HCC, acute hepatic failure, variceal bleeding, acute kidney injury, pulmonary lipiodol embolization, femoral artery pseudoaneurysm, femoral arteriovenous fistula, abdominal aortic dissection, spinal cord injury, and others. Complications after TACE are occasionally fatal. Therefore, it is important that we are well acquainted ourselves with these complications, and need care promptly the patient who develop symptoms of complication.

Clinical Safety and Efficacy of JX-594, a Targeted Multi-Mechanistic Oncolytic Pox Virus in Advanced Hepatocellular Carcinoma: Jeong Heo; Journal of the Korean Liver Cancer Study Group. 2011;11(2):149-154. Published online September 30, 2011

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Abstract PDF: JX-594 is a targeted oncolytic vaccinia virus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ras pathway activation. Direct oncolysis plus granulocyte macrophage-colony stimulating factor (GM-CSF) expression is accompanied by tumor vascular shutdown and anti-tumoral immunity. In a Phase 1 trial, JX-594 injection into hepatocellular carcinoma (HCC) was well-tolerated and associated with viral replication, anti-cancer immunity, decreased tumor perfusion and tumor necrosis. JX-594 has been shown to be well-tolerated by intravenous (IV) infusion and intratumoral (IT) injection and JX-594 is being developed as a novel therapy for patients with refractory or advanced HCC. Synergistic anti-tumor effects are predicted with JX-594 and sorafenib due to acute vascular shut down effect and tumor-specific antibody formation of JX-594 and chronic anti-angiogenic effects of sorafenib. JX-594 shows promise as a novel agent for the treatment of advanced HCC.

Case Reports

A Case of Early and Massive Recurred Hepatocellular Carcinoma in Patients with Ruptured Hepatocellular Carcinoma Underwent Staged-Surgical Resection: Sung Hoon Kim, Jin Hong Lim, Sang Hoon Ahn, Kyung Sik Kim; Journal of the Korean Liver Cancer Study Group. 2011;11(2):155-159. Published online September 30, 2011

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Abstract PDF: The rupture of hepatocellular carcinoma (HCC) has been uncommon complication. Because the diagnosis of early HCC has been increase due to development of imaging modality and surveillance program, the incidence of ruptured HCC has been decreased. The paradigm of treatment for ruptured HCC has shifted from surgical hemostasis to transcatheteric chemoembolization (TACE) at acute phase. After the control of acute phase, the definitive treatment for HCC is still debate. However, many studies have advocated staged-liver resection. Some studies reported that the patients underwent staged-liver resection showed a similar survival rate compared with survival rate in patient with non-ruptured HCC. The staged-liver resection was usually performed in the patients with well-preserved liver function. The decision of optimal time for surgery after TACE and surgical indications for ruptured HCC after any other primary treatment are controversy. We experienced a cases of early and massive recurrence HCC in patients with well-preserved liver function and the rupture of HCC. The further study may be needed to decide the optimal time of surgery after TACE and surgical indication for rutprued-HCC.

A Case of Concurrent Liver Resection and Splenectomy in Patients with Hepatocellular Carcinoma and Decompensated Liver Cirrhosis: Sung Hoon Kim, JIn Hong Lim, Sang Hoon Ahn, Kyung Sik Kim; Journal of the Korean Liver Cancer Study Group. 2011;11(2):160-164. Published online September 30, 2011

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Abstract PDF: Hepatocellular carcinoma (HCC) develops on chronic liver disease and often accompanies portal hyperternsion. Portal hypertension induces hypersplenism with splenomegaly. Because hypersplenism results in pancytopenia, especially thrombocytopenia, it is not easy to decide the hepatic resection for many surgeons in patients with HCC and hypersplenism. Although liver transplantation is the most ideal treatment for HCC and hypersplenism, liver resection has been performed commonly because of donor shortage. Splenectomy has performed to control intractable varices as a Hassab’s operation (=decongestion of upper gastric marginal veins and splenectomy). Recently, as a development of surgical techniques and equipments, especially laparoscopic surgery, splenectomy has been performed safely and easily. Some studies reported that splenectomy improved the liver function. Splenectomy in patients with HCC expanded the indication of liver resection and increased disease free survival (DFS). However, portal vein thrombosis (PVT) is a one of well-recognized complications of splenectomy and recent prospective study reported the 50% rate of PVT in non-cirrhotic splenectomized patients. Some studies reported that splenectomy with simultaneously or staged liver resection was performed safely without a significant complication and operative mortality. We experienced a case that underwent simultaneously liver resection and splenectomy and then recovered without complication. The further study may be needed to evaluate the role of splenectomy in patients with HCC and hypersplenism.

A Case of Paraplegia after Successful Treatment of Cyberknife for Hepatocellular Carcinoma: Geum Youb Noh, Chul Ju Han, Youn Joo Kim, Ki Young Yang, Su Cheol Park, Jin Kim, Yu Cheol Kim, Mi Sook Kim; Journal of the Korean Liver Cancer Study Group. 2011;11(2):165-171. Published online September 30, 2011

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Abstract PDF: Radiation therapy (RT) is one of the managements for unresectable hepatocellular carcinoma (HCC). Traditionally, RT has played only a limited role in HCC treatment because of its low efficacy and the low tolerance of the liver for this modality. However, as the technology of RT grows rapidly in recent years, indication of RT for HCC has been extended remarkably. Stereotactic body radiation therapy (SBRT) is a technique that allows precise delivery of a large ablative radiation dose to the tumor while sparing normal surrounding tissue in 1 to 5 fractions. As RT becomes useful therapeutic strategy, the important problem is that there could be serious complication after RT. Here we present a case of 54 years old male with advanced stage of HCC, who underwent a serious neurologic complication of paraplegia following Cyberknife (CK) treatment. He had a huge HCC in right lobe of the liver, and initially transarterial chemoembolization (TACE) was performed with an unsatisfactory response. Therefore, CK was performed, and another TACE was done for a new lesion, which was followed by remarkable complete remission of the tumor. However, paraplegia developed in both of his lower extremities a year after CK. Investigation has shown radiation myelitis as the cause of paralysis. Three and a half years have passed since CK treatment, and HCC is still in complete remission state, however, paraplegia is persistent now. Radiation myelitis should be considered as a complication, when CK is applied to treatment of HCC.

A Case of Intractable Duodenal Ulcer Bleeding Followed by Hepatic Abscess after Transarterial Chemoembolization on Recurrent Hepatocellular Carcinoma: Keun Soo Ahn, Koo Jeong Kang, Young Hoon Kim, Tae Jin Lim; Journal of the Korean Liver Cancer Study Group. 2011;11(2):172-177. Published online September 30, 2011

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Abstract PDF: Transarterial chemoembolization (TACE) is widely used in patients with hepatocellular carcinoma (HCC). Although this procedure is being performed safely and effectively, severe complications including liver abscess, upper gastrointestinal bleeding and liver failure can be rarely occurred. A 63-year-old female patient was admitted due to hematochezia for 1 day. She underwent central bisectionectomy for HCC 3 months ago. On follow up computed tomography, large recurred HCC was found at left lateral section and she underwent TACE. Ten days after TACE, she complained anorexia, general weakness and hematochezia and admitted. On gastroduodenoscopy, diffuse and shallow ulcer with bleeding was noted at duodenal bulb and it was controlled by epinephrine injection. However, recurrent ulcer bleeding was occurred and she underwent a dozen times of endoscopic intervention and one time of angiographic intervention to control bleeding. Although ulcer bleeding was stopped, it was followed by liver abscess in the left lateral section. The abscess was drained by pig-tail catheter, however the patient resulted in dead by hepatic failure. It is hard to manage the severe complications after TACE, therefore TACE should be applied judiciously including super selection of hepatic artery and early detection of complications and appropriate management is necessary.

A Case of Hepatocellular Carcinoma Recurred Extensively during Treatment of Biliary Complication Occurring after Transarterial Chemoembolization: Hyun Jung Oh, Hana Park, Kwang Hoon Lee, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Chae Yoon Chon, Jun Yong Park; Journal of the Korean Liver Cancer Study Group. 2011;11(2):178-184. Published online September 30, 2011

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Abstract PDF: Hepatocellular carcinoma(HCC) is one of the cancers with poor prognosis. Transarterial chemoembolization(TACE) has been widely used for treating unresectable HCC. Although TACE is considered as a less invasive and relative safe procedure, severe complications such as hepatic failure, pulmonary embolism, liver abscess, biloma formationcan occur rarely after TACE. These complications sometimes may lead to fatal clinical situation, even death. We reported a case of HCC recurred extensively during treatment of biliary complication after TACE. A 44-year-old male with HCC was admitted due to fever for 3 days after undergoing TACE. Three weeks before the admission, he had been diagnosed with HCC recurrence which presented as two arterial enhancing nodules in MRI and treated with TACE. CT scan showed 7 cm sized air containing fluid collections with necrosis suggestive of liver abscess and 15 cm sized biloma formation. Because the patient was in septic shock at admission, percutaneous catheter drainage was performed with use of broad spectrum antibiotics. After treatment of 3 months, the sizes of hepatic abscess and biloma were remarkably decreased. However, 1 month later, large size tumor recurrence and perihepatic lymph node metastasis were found on a follow-up CT scan. In this case, the cause of rapid growing recurrence after TACE is uncertain, but the development of unanticipated complication seems to affect the progression to poor prognosis. Therefore, early recognization of predisposing factors with proper management would be needed to prevent these serious complications after TACE.

Conus Medullaris Syndrome after Transcatheter Arterial Chemoembolization in Patient with Hepatocellular Carcinoma: Sun Hong Yoo, Si Hyun Bae, Pil Soo Sung, Hee Yeon Kim, Do Seon Song, Myeong Jun Song, Jong Young Choi, Seung Kew Yoon, Ho Jong Chun; Journal of the Korean Liver Cancer Study Group. 2011;11(2):185-189. Published online September 30, 2011

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Abstract PDF: Hepatocellular carcinoma (HCC) is the fourth most common cancer in Korea and a common cause of cancer death. Transcatheter arterial chemoembolization (TACE) is used as palliative therapy for patients with inoperable HCC. TACE is an effective treatments for inoperable HCC, but variable complications due to using embolic agents can occur after TACE. Complications due to embolic agents include pulmonary lipiodol embolism, splenic infarction, cerebral lipiodol infarction, and spinal cord injury. This is a rare case of spinal cord injury after a sixth TACE via right T9 intercostal artery.

A Case of Aggressive Treatment with Transarterial Embolization Using Drug-Eluting Beads for Hepatocellular Carcinoma in Decompensated Liver Cirrhosis Patient: Eileen L. Yoon, 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. 2011;11(2):190-194. Published online September 30, 2011

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Abstract PDF: Conventional transarterical chemoembolization (TACE) is the first-line treatment for patients with intermediate stage of hepatocellular carcinoma (HCC). However, irreversible liver failure after the procedure is one of the most feared complications and therefore, decompensated Child-Pugh C patients may not be the indication of the conventional TACE. Drug-eluting beads loaded with doxorubicin is a novel drug delivery embolization system and reported to have non inferior efficacy compared to conventional TACE. Also drug-eluting beads loaded with doxorubicin is associated with lower rates of acute liver failure after the procedure and lower rates of systemic toxicity of the chemotherapeutic agents. Herein, we report a case of aggressive treatment with transarterial embolization using drug-eluting beads loaded with doxorubicin for HCC in decompensated liver cirrhosis patient who was not eligible for conventional TACE treatment.

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