Treatment of hepatocellular carcinoma

Hepatocellular carcinoma is one of the most common cancers worldwide. The incidence of this disease is also increasing in the Western world. Typically, HCC is diagnosed when patients have already reached an advanced stage of the disease and the prognosis is poor. Potentially curative treatment options include surgical resection or liver transplantation and can be offered to patients with adequate liver function and tumour stage. Other non-surgical treatment options such as radiofrequency ablation, cryoablation, ethanol or acetic acid injection, transarteriel chemoembolisation radiation therapy and systemic chemotherapy can be offered either alone or in combination to selected groups of patients. These treatments can improve (tumour-free) survival and in a few cases even cure the patient.     

Treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. The major etiologies and risk factors for HCC development are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for early HCC detection in patients at risk, patient survival has not improved during the last three decades. This is due in part to the advanced stage of the disease at the time of clinical presentation, in part due to the limited therapeutic options. These fall into four main categories: (1) surgical interventions, including tumour resection and liver transplantation, (2) percutaneous interventions, including ethanol injection and radiofrequency thermal ablation, (3) transarterial interventions, including embolisation and chemoembolisation and (4) drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomised controlled clinical trials that are the basis for therapeutic recommendations. While surgery and percutaneous as well as transarterial interventions are effective in patients with limited disease (1-3 lesions, < 5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce morbidity and mortality from HCC, therefore, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Further, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should further elucidate the molecular events underlying HCC development and identify novel diagnostic markers as well as therapeutic and preventive targets.     

Treatment of hepatocellular carcinoma

Opinion statement Hepatocellular carcinoma is the fifth leading cause of cancer worldwide and its incidence is increasing. Surveillance programs allow doctors to identify patients at early stages of the disease, when the tumor may be curable by radical treatments such as resection, liver transplantation, or local ablation. In the West, these treatments can be applied to 30% to 40% of patients. Resection yields favorable results in patients with single tumors and a well-preserved liver function (5-year survival rate is 60%). Recurrence complicates two thirds of the cases, and there is no effective adjuvant treatment. Liver transplantation is the best treatment for patients with single tumors that are less than 5 cm in diameter and liver failure, or in those presenting with three nodules less than 3 cm, but organ shortage greatly limits its applicability. Long-term survival is expected to be around 50% to 70% at 5 years depending upon the drop-out rate of patients on the waiting list. Chemoembolization and local ablation are the neo-adjuvant treatments applied to patients on the waiting list to prevent tumor progression; no controlled study proving their efficacy has yet been published. In nonsurgical candidates, percutaneous treatments (ethanol injection or radiofrequency ablation) are the best therapeutic approach and improve survival in Child-Pugh A class patients with small tumors that achieve initial complete response (5-year survival rate is 40% to 50%). At more advanced stages, chemoembolization, a technique combining intra-arterial chemotherapy and selected ischemia, has shown to slightly improve survival in a meta-analysis of randomized trials. No survival advantages have been demonstrated with intra-arterial or systemic chemotherapy, hormonal compounds, or radiation. New agents, such as inhibitors of the tyrosine kinase receptors of growth factors and antiangiogenic agents, are currently being tested in phase II/III trials.     

Treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third cause of cancer-related death. Despite therapeutic advances, the overall survival of patients with HCC has not significantly improved in the last two decades. In the majority of the cases there is underlying cirrhosis, so the prognosis of HCC depends on not only tumor stage but also liver function. There is not a widely accepted HCC staging system. In our group we have developed a new staging classification that stratifies HCC patients into four major categories and simultaneously links staging with treatment. Patients at an early stage are those who present with an asymptomatic single HCC with a maximum diameter of 5cm or up to three nodules each less than 3cm. They will benefit from curative therapies, including resection, liver transplantation (LT), and percutaneous ablation. Patients exceeding these limits, but who are free of cancer-related symptoms and vascular invasion or extrahepatic spread fit into the intermediate stage and may benefit from palliation with chemoembolization. The patients with mild cancer-related symptoms and/or vascular invasion or extrahepatic spread are included in the advanced stage. In this stage there is not effective therapy, and these patients may profit from new therapies in the setting of randomized controlled trials (RCTs). Finally, the patients with severe cancer-related symptoms or great tumor burden belong to the terminal stage and only benefit from symptomatic treatment.     

Treatment of hepatocellular carcinoma

Hepatocellular carcinoma develops in more of 90% of patients in the setting of cirrhosis. The increasing prevalence seems related with the wide-spread distribution of hepatitis C virus infection, as 80% of cases arise on chronic infection caused by this agent. Either conventional resection or orthotopic liver transplantation are often curative but suitable for few patients, If the surgical approach is not adequate, percutaneous ablation using ethanol injection or radiofrequency current may be considered. However, only 15-20% of patients can benefit from these therapies. Chemoembolization is considered when the previous options are contra-indicated but benefits on survival are still a matter of debate. The impact of new agents as tamoxifen, interferon o diverse chemotherapies on both survival and symptoms also remains to be stablished.     

Treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and is the third highest cause of cancer-related mortality. HCC usually develops in patients with chronic liver disease, particularly in those who also have cirrhosis. The possibility of curative treatment depends on both the stage of tumor and liver function. Effective treatments for HCC include percutaneous ablation, surgical resection, and liver transplantation. Both percutaneous ablation and surgical resection provide a high rate of complete responses and are assumed to improve survival that should exceed 50% at 5 years. Liver transplantation results in a better survival rate, and is not contraindicated by advanced liver dysfunction. However, its application is limited by the scarcity of donor organs. Treatments for advanced HCC include transarterial chemoembolization and chemotherapy. Although short-term prognosis of HCC patients has improved recently due to advances in early diagnosis and treatment, long-term prognosis is as yet far from satisfactory due to frequent recurrence. Prevention of recurrence of HCC remains one of the most challenging tasks in current hepatology.     

Treatment of hepatocellular carcinoma

Summary. Treatment of patients with hepatocellular carcinoma (HCC) is largely influenced by local resources and the clinical stage of the disease. Hepatic resection is the treatment of choice for patients with HCC and normal liver. Tumour size and number, and liver status are common guidelines for choosing treatment in patients with cirrhosis. Hepatic resection and liver transplantation offered the best chances of cure in patients with a single small tumour. The 3-year survival of these patients was definitively better than that of historical controls. In the setting of patients with well-preserved liver function, a controlled study comparing the cost-efficacy of resection and transplantation is deemed necessary by many, but it is hardly feasible for both ethical and practical considerations. One major drawback of surgery in patients with a small tumour is early tumour spread to regional lymph-nodes, which favours early tumour recurrence after operation. Patients with more advanced tumour disease were rarely eligible for surgery and had dismal prognoses. For those with small tumours who were not eligible for surgery, percutaneous ethanol injection appeared to be a cost-saving and effective treatment modality. Arterial embolization is the only recom-mendable palliative treatment of patients with large tumours and poor hepatic function.     

Treatment of hepatocellular carcinoma in cirrhotic patients

Hepatocellular carcinoma (HCC) is a frequent tumor with increasing incidence in relation with hepatitis C virus infection endemic. Known treatments are rather unsatisfactory and only liver transplantation, surgical resection or percutaneous ablation are considered as curative options for HCCs of small size. No palliative therapeutic option has clearly demonstrated any benefit on overall survival. While standard antineoplastic options as systemic chemotherapy and external radiotherapy are unsatisfactory, conformal radiotherapy and proton therapy might be of interest. Interferon and differentiating agents could probably play a key role in modulating liver oncogenesis while they have rather poor efficacy for controlling tumor growth. Primary and secondary chemoprophylaxis of HCC as well as neoadjuvant and adjuvant options have to be developed to improve the prognosis of this tumor.     

Treatment of spontaneous ruptured hepatocellular carcinoma.

BACKGROUND/AIMS: Spontaneous rupture with bleeding is a potentially life-threatening complication of hepatocellular carcinoma (HCC). We review our experience with treatments of ruptured HCC. METHODOLOGY: Between January 1988 and December 1997, 18 patients with ruptured HCC were admitted. The patients were divided into 4 groups according to the treatment type of ruptured HCC. Group 1 consisted of 10 patients treated by transarterial embolization (TAE) followed by elective hepatectomy. Group 2 consisted of 2 patients treated by only TAE. Group 3 consisted of 3 patients treated by emergency operation. Group 4 consisted of 3 patients who could not be treated by TAE or surgery. RESULTS: In Group 1, 4 of the 10 patients died; 3 from recurrent HCC and 1 from cerebral hemorrhage, and hospital mortality was absent. The 1-year survival rate was 87.5%. In Group 2, both patients recovered sufficiently well to be discharged. The 1-year survival rate was 50%. In Groups 3 and 4, hospital mortality rate was 100%. CONCLUSIONS: TAE followed by elective hepatectomy was an effective treatment in patients with ruptured HCC.     

Treatment strategies for hepatocellular carcinoma in Japan

The main methods of treatment for hepatocellular carcinoma (HCC) in Japan are hepatic resection, radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Meticulous follow up is then undertaken to check for recurrence, which is treated using repeated RFA or TACE. Hepatic arterial infusion chemotherapy has been introduced as treatment for advanced HCC, and the molecular‐targeted drug sorafenib is also now available. Rigorous medical care using these treatment methods and early diagnosis mean that the prognosis for HCC in Japan is the best in the world. This paper reviews the treatment strategies for HCC in Japan.     

Treatment of hepatocellular carcinoma in Child-Pugh B patients

Background

The frequency with which patients in Child-Pugh B having hepatocellular carcinoma are treated following the international guidelines according to the Barcelona Clinic Liver Cancer stages is unknown.

Aims

To investigate treatment allocation for Child-Pugh B patients in different tumour stages, with particular interest in the intermediate stage.

Methods

Patients were retrospectively identified from a consecutively collected series. Treatment was carried out primarily according to the guidelines.

Results

Of 86 Child-Pugh B patients, 45 were Barcelona early stage, of which the Child-Pugh scores were 46.7% B7, 33.3% B8, 20.0% B9; 27 patients were intermediate stage (B7 59.3%, B8 37.0% and B9 3.7% respectively), 12 were advanced (41.7% B7, 25.0% B8 and 33.3% B9) and 2 were terminal (both B9). In the intermediate stage, transarterial chemoembolization (or ablation) was performed in 68.8% of the Child-Pugh B7 patients, 50% of the B8 patients and 0% of the B9 patients. Median survival of the intermediate patients was 8.0 months (9.0 in B7 vs. 6.0 in -B8/B9, P = 0.048). Survival of the intermediate stage patients undergoing chemoembolisation was 22.0 months in Child-Pugh B7 and 6.0 in B8.

Conclusions

Approximately half of the intermediate stage patients can undergo locoregional treatment with good survival when in the Child-Pugh B7. The Child-Pugh numeric score impacts survival, suggesting that this tumour stage be refined.     

Treatment of hepatocellular carcinoma by percutaneous interventional methods

In the treatment of early and intermediate hepatocellular carcinoma the range of indications for percutaneous ablation techniques is becoming wider than surgery or intra-arterial therapies. Indeed, whereas for some years only patients with up to three small tumors were treated, with the introduction of the single-session technique performed under general anesthesia, even patients with more advanced disease are now being treated. Although it is understood that partial resection assures the highest local control, the survival rates after surgery are roughly comparable with percutaneous ethanol injection. The explanation is due to a balance among advantages and disadvantages of the two therapies. Percutaneous ethanol injection survival curves are better than curves of resected patients who present adverse prognostic factors, and this means that surgery needs a better selection of the patients. Indications for both of these therapies are reported. An open question remains about the choice between percutaneous ethanol injection and other new ablation procedures. In our department we currently use radiofrequency ablation in the majority of patients but consider percutaneous ethanol injection and segmental transarterial chemoembolization complementary, and use them according to the features of the disease and the response. Evaluation of their therapeutic efficacy, techniques and results are reported.     

Treatment of hepatocellular carcinoma by percutaneous laser hyperthermia

BACKGROUND: AND AIM: The majority of patients with hepatocellular carcinoma (HCC) are unsuitable for partial liver resection or transplantation because of unfavorable tumor characteristics or underlying severe liver disease. Techniques of in situ tumor ablation may be an alternative to resection and have the advantage of reduced morbidity and mortality. Percutaneous laser-induced hyperthermia produces predictable areas of tumor necrosis with minimal complications. This study assesses the effectiveness of percutaneous interstitial laser hyperthermia in eight patients with hepatocellular carcinoma occurring on a background of chronic liver disease. METHODS: Patients with confirmed HCC with less than five tumor nodules of less than 7 cm maximum diameter were selected for treatment. Tumor response was monitored by dynamic CT, alpha-fetoprotein levels and liver function tests. Patients were discharged within 24 h. RESULTS: There were six males and two females, with liver disease of Child-Pugh grade C in five, and grade B in the others. Two patients had tumor recurrence following previous segmental resection. Four had solitary lesions, and individual lesion size ranged between 3 and 7 cm. Avascularity and significant necrosis of the tumor was achieved on all lesions less than 4 cm, but was unsuccessful in tumors greater than 5 cm despite repeated treatments. Survival of patients ranged from 3 to 18 months. CONCLUSIONS: Percutaneous laser hyperthermia produces significant tumor necrosis and has the advantage of low morbidity, and cost effectiveness. Further refinement is needed to achieve elimination of viable tumor cells at the tumor host interface by further knowledge of appropriate dosimetry levels, manipulation of blood flow and synergistic effects with other therapeutic modalities.