8Treatment of hepatocellular carcinoma
Section snippets
HCC staging and natural course
For the staging of HCCs five systems have been proposed for the assessment of the extent and of the prognosis of the disease: the Okuda staging system (Table 228), the TNM classification and its modification by the ‘Union International Contre Cancer (UICC)’, the ‘Barcelona Clinic Liver Cancer (BCLC)’ classification (Table 329), and the ‘Cancer of the Liver Italian Program (CLIP)’ score (Table 430). The Okuda staging system is very effective for the identification of a subgroup of patients
Treatment of HCC
Therapies for HCC can be devided into four categories: surgical interventions (tumour resection and liver transplantation), percutaneous interventions (ethanol injection, radiofrequency thermal ablation), transarterial interventions (embolisation, chemoperfusion, or chemoembolisation) and drugs, including gene and immune therapy (Figure 2). Potentially curative therapies are tumour resection, liver transplantation, and percutaneous interventions that can result in complete responses and
Resection
In patients without concomitant liver cirrhosis (5% in Western countries, 40% in Subsahara Africa and Asia) HCC resection is the treatment of choice with low rates of life-threatening complications. By comparison, in the majority of patients with cirrhosis, strict selection is required to avoid resection-related complications, especially postoperative liver failure. Apart from bilirubin and albumin concentration as well as platelet count and indocyanine green clearance,31, 32 a recent study
Percutaneous interventions
Percutaneous interventions are the best options for small unresectable HCCs.44 Tumor ablations can be achieved chemically by percutaneous ethanol injection (PEI) or acetic acid injection (PAI) or thermally by radiofrequency thermal ablation (RFTA), microwave-heat induced thermotherapy (HiTT), laser induced thermotherapy (LiTT), or cryoablation. Apart from percutaneous interventions, these techniques can be applied also laparoscopically or after laparotomy.
Transarterial interventions
Transarterial embolisation and chemoembolisation are the most widely used treatments for HCCs that are unresectable or cannot be effectively treated by percutaneous interventions).51, 52, 53, 54 Embolisation agents may be administered alone (embolisation) or after selective intra-arterial chemotherapy (generally doxorubicin, mitomycin or cisplatin) mixed with lipiodol (chemoembolisation). Transarterial embolisation or chemoembolisation results in partial responses in 15–55% of patients, delays
Drugs
A number of systemic chemotherapies, hormonal and other drugs (Table 5) have been evaluated in clinical trials.56, 57, 58 While most chemotherapeutic agents, tamoxifen,59 octreotide60 and interferon51 have not been shown to be effective in randomised controlled clinical trials, there are a number of substances that may deserve further clinical evaluation, e.g. gemcitabine,61, 62 thymostimulin,63 α-1-thymosin,64 pravastatin,65 thalidomide,66 megestrol acetate,67 several antiangiogenic small
Future treatment strategies
In view of the limited therapeutic options for advanced HCCs a number of experimental strategies are being evaluated (Figure 4), incl. gene and immune therapies based on suicide, cytokine and antiangiogenic genes or DNA vaccination with tumour-specific genes,68, 69 oncolytic viruses70 as well as novel drugs, e.g. 3-bromopyruvate.71
HCC prevention
HCC prevention falls into two categories. Primary prevention that is aimed at the prevention of HCC development in patients with chronic liver diseases of different etiologies and secondary prevention that is aimed at preventing the recurrence and/or the development of new HCC lesions after successful surgical or non-surgical HCC treatment.
Summary and perspectives
HCC is one of the most common malignant tumours in some areas of the world with an extremely poor prognosis. HCC treatment is based on randomised controlled trials and many observational studies. Treatment options fall into four main categories: (1) surgical interventions, incl. tumour resection and liver transplantation, (2) percutaneous interventions, incl. ethanol injection and radiofrequency thermal ablation, (3) transarterial interventions, incl. embolisation and chemoembolisation and (4)
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Advances in drug delivery for post-surgical cancer treatment
2019, BiomaterialsCitation Excerpt :With this multilayer structure, a successive release profile of DCA and oxaliplatin was obtained. 50%–80% hepatocellular carcinoma (HCC, the most common type of liver cancer) patients suffered from the postoperative recurrence [94–96]. In another example, Liu et al. developed a controlled drug release asymmetric multilayer polylactide nanofiber (AMPN) mats to inhibit post-surgical liver cancer recurrence [97].
Use of asymmetric multilayer polylactide nanofiber mats in controlled release of drugs and prevention of liver cancer recurrence after surgery in mice
2015, Nanomedicine: Nanotechnology, Biology, and MedicineInvolvement of catalase in the apoptotic mechanism induced by apigenin in HepG2 human hepatoma cells
2011, Chemico-Biological InteractionsCitation Excerpt :The incidence of HCC has tripled in the United States over the past two decades as a result of an increase in hepatitis C infections [1,2]. Current treatment options for HCC remain limited, therefore, development of more-effective therapeutic tools and strategies is greatly desirable [3]. In order to develop an effective drug against several types of cancer, considerable attention has been devoted to identifying plant-derived compounds displaying anti-tumor activity, such as the flavonoids [4].
Radiochemotherapy of hepatocarcinoma via lentivirus-mediated transfer of human sodium iodide symporter gene and herpes simplex virus thymidine kinase gene
2011, Nuclear Medicine and BiologyCitation Excerpt :While surgery and percutaneous as well as transarterial interventions are effective in patients with limited disease (1–3 lesions, <5 cm in diameter), at the time of diagnosis, more than 80% of patients present with multicentric hepatocarcinoma and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. Furthermore, adjuvant therapy for prevention of recurrences after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with hepatocarcinoma [27]. Unfortunately, both systemic chemotherapy and targeted therapy provide only limited efficacy.
Applicability of staging systems for patients with hepatocellular carcinoma is dependent on treatment method - Analysis of 2010 Taiwanese patients
2009, European Journal of CancerCitation Excerpt :Regular sonographic examination can help detect small HCC early,4 and many therapeutic modalities are available for HCCs.3 However, 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.5 Staging systems are used to define prognosis and treatment options.