Biological Therapy ; Carcinoma, Hepatocellular ; drug therapy ; radiotherapy ; therapy ; Humans ; Liver Neoplasms ; drug therapy ; radiotherapy ; therapy ; Radiography, Interventional ; Ultrasonic Therapy

Hepatocellular carcinoma (HCC) is one of the most critical global health issues. With frequent association of viral liver disease, HCC is highly complex, harboring both cancer and chronic liver disease. The tumor stage and underlying liver function are both major determinants of the treatment selection as well as prognosis in HCC patients, thus allowing no more than a 20% chance for potentially curative therapies. Radiotherapy technology has been evolved remarkably during the past decade, and radiation can be precisely delivered, thereby permitting higher doses to the tumour and reduced doses to surrounding normal tissues. There has been increasing interest in the merits of radiotherapy in HCC over the past few years, as indicated by a Pub Med search. Radiotherapy has been used as the definitive therapy with curative intent in early stage tumours. It has been used also in combination with TACE for intermediate stage tumours. In locally advanced tumours, radiotherapy has been combined with systemic agents. Despite its efficacy, radiotherapy has not yet been incorporated into the standard management guidelines of HCC. The lack of high evidence level data, especially randomized controlled trials, has posed an obstacle in including radiotherapy into the routine treatment schema of HCC. Therefore, well-designed prospective studies are strongly recommended using developing technology for radiotherapy alone or combination therapies. Also, many issues such as the optimal dose-fractionation, intra- or extrahepatic metastasis after radiotherapy, and radiation-induced hepatic dysfunction remain to be solved. In this review, current status of radiotherapy for HCC will be discussed with regard to technical consideration and combination strategy. The limitation and future perspectives will also be discussed.
Carcinoma, Hepatocellular/drug therapy/radiography/*radiotherapy ; Humans ; Liver/radiation effects ; Liver Neoplasms/drug therapy/radiography/*radiotherapy ; Neoplasm Metastasis ; Radiation Dosage ; Radiotherapy, Adjuvant/adverse effects/methods ; Treatment Outcome

BACKGROUND/AIMS: There has been no standard treatment for advanced hepatocellular carcinoma (HCC) until now. The aim of this study was to evaluate the efficacy of hepatic arterial infusion therapy (HAIT) using 5-fluorouracil (5-FU) and cisplatin (CDDP) for advanced HCC. METHODS: Twenty patients received repeated HAIT using an implanted drug delivery system. Of the 20 patients, eight patients had HCC with portal vein tumor thrombosis (PVTT), eleven patients had residual tumor despite transcatheter arterial chemoembolization (TACE) or percutaneous ethanol injection therapy (PEIT), and one patient had multiple recurrent HCC nodules after surgical resection. The patients were repeatedly treated with an arterial infusion of 5-FU (250 mg/5 hours on day 1-5) and CDDP (10 mg/1 hour on day 1-5) via the drug delivery system at three weekly intervals. RESULTS: Of the 20 patients, three patients were excluded from the study due to death within the first 1 week of treatment or during follow-up before evaluation. The response rate according to tumor size on abdominal CT was 29.4% (5 patients). One of the five patients showed a complete response (CR, 5.9%), three patients showed partial responses (PR, 17.6%), and one patient showed a minor response (MR, 5.9%). Chemotherapy- related side effect, such as grade I-II nausea (n=2), grade II vomiting (n=1), fever (n=1), drug eruption (n=1) and catheter-related complication such as dislodgement of the catheter (n=2), occurred in six patients. CONCLUSIONS: HAIT using the FP regimen is another option for patients having advanced HCC with PVTT or for patients showing an ineffective response to other therapies.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy/radiography ; Cisplatin/administration & dosage ; English Abstract ; Fluorouracil/administration & dosage ; *Hepatic Artery ; Humans ; Infusion Pumps, Implantable ; *Infusions, Intra-Arterial ; Liver Neoplasms/*drug therapy/radiography ; Male ; Middle Aged

Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.
Aged ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Hepatocellular/drug therapy/physiopathology/*radiography ; Female ; Humans ; Liver Neoplasms/drug therapy/physiopathology/*radiography ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Niacinamide/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/*therapeutic use ; Tomography, X-Ray Computed

OBJECTIVETo explore the feasibility and outcome of radiofrequency ablation (RFA) in blocking feeding vessels of hypervascular hepatocellular carcinoma (HCC).

METHODSTotally 101 patients pathologically confirmed hypervascular HCC were included in the study. In percutaneous arterial ablation (PAA) + RFA group, 71 patients with 74 HCC underwent PAA before classical RFA of the other regions of the tumors, while in the RFA group, another 83 patients with 102 HCC were treated with RFA directly. For another 30 patients who responded poorly to transcatheter arterial chemoembolization were treated with percutaneous arterial embolization (PAE), followed by RFA; another 23 patients were treated with RFA alone were regarded as the control group. Contrast-enhanced CT and magnetic resonance imaging were used as post-RFA imaging follow-up at 1, 3, and 6 month.

RESULTSIn PAA + RFA group, post-PAA imaging showed blocked blood flow in 65 (87.8%) HCC. There were average 2.76 +/- 1.12 ablated foci per HCC in PAA + RFA group and 3.36 +/- 1.60 ablated foci per HCC in control group (P = 0.01). The tumor necrosis rate at 1 month after RFA was 90. 5% (67/74) in PAA + RFA group and 90.2% (92/102) in control group. HCC recurrence rate at 6 month after RFA was 17.6% (13/74) in PAA + RFA group and 31.4% (32/102) in control group (P = 0.038). In PAE + RFA group, 88.6% of the main feeding vessels were blocked. The tumor necrosis rate at 1 and 6 month after FRA was 92.6% (25/27) and 85.2% (23/27) in PAA + RFA group and 65.2% (15/ 23) (P = 0.030) and 56.5% (13/23) (P = 0.024) in control group.

CONCLUSIONPAA and PAE can block the feeding vessels of HCC, enhance the ablated necrosis in the tumor, decrease post-RFA recurrence, and therefore provides a safe and feasible method for treating hypervascular HCC.

Aged ; Carcinoma, Hepatocellular ; blood supply ; diagnostic imaging ; drug therapy ; therapy ; Catheter Ablation ; Chemoembolization, Therapeutic ; Female ; Humans ; Liver Neoplasms ; blood supply ; diagnostic imaging ; drug therapy ; therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Radiography

OBJECTIVE: To assess the technical feasibility and local efficacy of percutaneous radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) for an intermediate-sized (3-5 cm in diameter) hepatocellular carcinoma (HCC) under the dual guidance of biplane fluoroscopy and ultrasonography (US). MATERIALS AND METHODS: Patients with intermediate-sized HCCs were treated with percutaneous RFA combined with TACE. RFA was performed under the dual guidance of biplane fluoroscopy and US within 14 days after TACE. We evaluated the rate of major complications on immediate post-RFA CT images. Primary technique effectiveness rate was determined on one month follow-up CT images. The cumulative rate of local tumor progression was estimated with the use of Kaplan-Meier method. RESULTS: Twenty-one consecutive patients with 21 HCCs (mean size: 3.6 cm; range: 3-4.5 cm) were included. After TACE (mean: 6.7 d; range: 1-14 d), 20 (95.2%) of 21 HCCs were visible on fluoroscopy and were ablated under dual guidance of biplane fluoroscopy and US. The other HCC that was poorly visible by fluoroscopy was ablated under US guidance alone. Major complications were observed in only one patient (pneumothorax). Primary technique effectiveness was achieved for all 21 HCCs in a single RFA session. Cumulative rates of local tumor progression were estimated as 9.5% and 19.0% at one and three years, respectively. CONCLUSION: RFA combined with TACE under dual guidance of biplane fluoroscopy and US is technically feasible and effective for intermediate-sized HCC treatment.
Aged ; Antibiotics, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Carcinoma, Hepatocellular/*drug therapy/radiography/*surgery/ultrasonography ; Catheter Ablation/*methods ; Chemoembolization, Therapeutic/*methods ; Combined Modality Therapy ; Disease Progression ; Doxorubicin/administration & dosage ; Ethiodized Oil/administration & dosage ; Feasibility Studies ; Female ; Fluoroscopy ; Humans ; Liver Neoplasms/*drug therapy/radiography/*surgery/ultrasonography ; Male ; Postoperative Complications ; *Radiography, Interventional ; Retrospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome ; *Ultrasonography, Interventional

BACKGROUND/AIMS: Advanced hepatocellular carcinoma (HCC) with multiple lung metastases has a poor prognosis with no effective treatment having been established. This study evaluated the outcomes of systemic chemotherapy for advanced HCC with multiple lung metastases. METHODS: Between January 2000 and December 2006, 68 patients were diagnosed with HCC presenting with multiple lung metastases. Sixteen patients in the terminal stage, such as Child-Pugh grade `C' or an Eastern Cooperative Oncology Group performance status exceeding grade 2, were excluded from the analysis. The following treatment modalities were applied: 26 patients received primary tumor treatment (transarterial chemoembolization or intra-arterial chemotherapy) with systemic chemotherapy, 10 patients received primary treatment only, 8 patients received systemic chemotherapy only, and 8 patients received highly supportive care. The treatment responses and median survival times for the modalities were analyzed and compared. RESULTS: The median age of the 52 analyzed patients (45 males) was 52.4 years. The most common etiology of HCC was chronic hepatitis B virus infection (n=44, 84.6%) followed by hepatitis C virus infection (n=2, 3.8%), with the etiology being unknown in 6 cases (11.5%). The treatment modality had no significant effect on the treatment response rate (P=0.432) or median survival time (133, 66, 74, and 96 days for primary tumor treatment with systemic chemotherapy, primary tumor treatment only, systemic chemotherapy only, and highly supportive care, respectively; P=0.067). CONCLUSIONS: We found that systemic chemotherapy was not effective in treating HCC presenting with multiple lung metastases. Improving the effectiveness of systemic treatment and selecting patients who would benefit from such treatment remains a major challenge.
Adult ; Carcinoma, Hepatocellular/*drug therapy/radiography/*secondary ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Data Interpretation, Statistical ; Female ; Humans ; Liver Neoplasms/*drug therapy/pathology/radiography ; Lung Neoplasms/radiography/*secondary ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Severity of Illness Index ; Survival Analysis ; Treatment Outcome

OBJECTIVE: We wanted to investigate the prevalence and causative factors of extrahepatic arterial blood supply to hepatocellular carcinoma (HCC) at its initial presentation and during chemoembolization. MATERIALS AND METHODS: Between February 1998 and April 2000, consecutive 479 patients with newly diagnosed HCC were prospectively enrolled into this study. A total of 1629 sessions of transcatheter arterial chemoembolization (TACE) were performed in these patients (range: 1-15 sessions; mean: 3.4 sessions) until April 2004. For each TACE procedure, we determined the potential extrahepatic collateral arteries (ExCAs) depending on the location of the tumor, and we performed selective angiography of all suspected collaterals that could supply the tumor. The prevalence of ExCAs and the causative factors were analyzed. RESULTS: At initial presentation, 82 (17%) of these 479 patients showed 108 ExCAs supplying tumors. Univariate analysis showed that tumor size (p < 0.01), patient age (p = 0.02), a surface location (p < 0.01), and a bare area location (p < 0.01) were significantly associated with the presence of ExCAs. Multiple logistic regression analysis showed that only tumor size was predictive of ExCA formation (p < 0.01, odds ratio = 1.737, confidence interval: 1.533 to 1.969). During repeated TACE sessions, 97 additional ExCAs were detected in 70 (14%) patients. The cumulative probability of ExCAs in patients with a large tumor (> or = 5 cm) was significantly higher than that for those patients with a small tumor (< 5 cm) (p < 0.01). CONCLUSION: The presence of ExCAs supplying HCC is rather common, and the tumor size is a significant causative factor for the development of these collateral arteries.
Neovascularization, Pathologic/*etiology/physiopathology/radiography ; Middle Aged ; Male ; Logistic Models ; Liver Neoplasms/physiopathology/*therapy ; Humans ; Female ; Collateral Circulation/drug effects/physiology ; Chemoembolization, Therapeutic/*methods ; Carcinoma, Hepatocellular/physiopathology/*therapy ; Angiography ; Aged, 80 and over ; Aged ; Adult

Hepatoblastoma usually occurs in children under the age of 2 years, with very few cases reported in adults. We experienced a case of adult hepatoblastoma in a 36-year-old female with chronic hepatitis B . She had experienced sudden onset abdominal pain. Her serum alpha-fetoprotein level was markedly elevated, and abdominal CT showed a 9-cm mass with internal hemorrhage in the right hepatic lobe with hemoperitoneum, so an emergency hepatic central bisectionectomy was performed. The initial histologic examination revealed that the mass mimicked combined hepatocellular carcinoma and cholangiocarcinoma with spindle-cell metaplasia of the cholangiocarcinoma element. Follow-up abdominal CT performed 3 months later showed a 5.5-cm metastatic mass in the left subphrenic area. Laparoscopic splenectomy with mass excision was performed, and hepatoblastoma was confirmed histologically. A histologic re-examination of previously obtained surgical specimens also confirmed the presence of hepatoblastoma. Metastatic hepatoblastoma was found at multiple sites of the abdomen during follow-up, and so chemotherapy with cisplatin, 5-fluorouracil (5-FU), and vincristine was applied, followed by carboplatin and doxorubicin . Despite surgery and postoperative chemotherapy, she died 12 months after symptom onset.
Adult ; Carcinoma, Hepatocellular/pathology ; Cholangiocarcinoma/pathology ; Cisplatin/therapeutic use ; Diagnostic Errors ; Doxorubicin/therapeutic use ; Drug Therapy, Combination ; Female ; Fluorouracil/therapeutic use ; Hepatitis B, Chronic/complications/diagnosis ; Hepatoblastoma/drug therapy/*pathology/radiography ; Humans ; Liver Neoplasms/drug therapy/*pathology/radiography ; Tomography, X-Ray Computed ; Vincristine/therapeutic use

Hepatocellular carcinoma (HCC) is a critical global health issue and the third most common cause of cancer-related deaths worldwide. The majority of patients who present HCC are already at an advanced stage and their tumors are unresectable. Sorafenib is a multi-kinase inhibitor of the vascular endothelial growth factor pathway and was recently introduced as a therapy for advanced HCC. Furthermore, studies have shown that oral sorafenib has beneficial effects on survival. However, many patients experience diverse side effects, and some of these are severe. Liver abscess development has not been previously documented to be associated with sorafenib administration in HCC. Here, we report the case of a HCC patient that developed a liver abscess while being treated with sorafenib.
Anti-Bacterial Agents/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy/radiography ; Clostridium/isolation & purification ; Clostridium Infections/drug therapy/microbiology ; Humans ; Liver Abscess/etiology/*microbiology ; Liver Neoplasms/*drug therapy/radiography ; Male ; Middle Aged ; Niacinamide/adverse effects/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/adverse effects/*therapeutic use ; Tomography, X-Ray Computed