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• W2034654528 abstract "See article on page 860 Hepatocellular carcinoma (HCC) is among the more common fatal solid tumours encountered worldwide. 1 Its incidence is steadily rising and 300 000 new cases are reported each year. 2,3 It is a unique cancer in the sense that the underlying aetiology is identifiable in most cases and it usually occurs in the background of chronic liver disease. In regions with high incidence of HCC, current or prior infection with hepatitis B virus is the dominant underlying aetiology. Among the patients with HCC, 70% are positive for hepatitis B surface antigen (HBsAg) and 90% are antibody to hepatitis B core antigen (anti-HBc) positive for antibodies. 4 In low-incidence areas for hepatitis B infection such as USA, Europe and Japan, 50–75% of patients with HCC are hepatitis C virus antibody (anti-HCV) positive. 5,6 In the series by Pawarode et al., which is reported in this issue of the journal, hepatitis B seems to be the dominant aetiological factor, as 70% of the patients with HCC were HBsAg positive, whereas only 9% were anti-HCV positive. 7 Studies from other parts of the world have shown that combinations of factors such as hepatitis B and C, alcoholism and hepatitis C, and aflatoxin and hepatitis B enhance carcinogenesis. 8,9 In the study by Pawarode et al., comprehensive evaluation for the presence of infection due to hepatitis viruses is lacking. Moreover, the authors have not mentioned the presence of other known aetiological factors for HCC, such as alcohol or aflatoxin. Thus, a comment on the interplay of various aetiological factors in the pathogenesis of HCC in Thailand is not possible from this study. 7 By the time patients with HCC present with symptoms due to the tumour per se, the disease is already too advanced for curative therapy. 10 In the study by Pawarode et al., most patients presented with advanced disease; 84% of them had Okuda stage II or III disease and 17% had metastatic disease. 7 The best outcome has been achieved in those patients who were detected during a screening programme or were found incidentally at the time of imaging studies or transplantation. 11 Unfortunately, none of the patients in this series were detected in the above manner. The choice of therapy depends on parameters such as tumour characteristics (size, number, number of lobes involved, portal vein involvement, metastasis, etc.), underlying liver function and expertise and facilities available in that particular centre. 11 Surgical resection is the best available form of therapy if the lesion is resectable and is preferably ≤ 5 cm in size. 11,12 Only 16% of the patients in the series by Pawarode et al. underwent resection, as the majority were considered unresectable. 7 The reasons for tumours being unresectable, although unspecified in this study, are usually poor functional status of the liver, presence of extrahepatic metastasis, large tumour size, multicentricity of the tumour or involvement of major vascular structures. 10,11 The highest resectability rate reported is 18% from Japan, among a population who were regularly screened for HCC. 13 The series by Pawarode et al. has reported higher than expected resectability rates, possibly because it has used less stringent criteria for patient selection. This possibly accounts for lower 1 year survival figures of 50% in this series, in contrast to other series where survival of 80% has been reported. 14,15 The 5-year survival in other series is 50%, as most of the patients succumb to their illness due to recurrent disease or poor liver function. The authors mention that the 5-year survival in the surgically resected group was 33%. However, they have not commented on how their patients were followed up for tumour recurrence and the incidence of the same in their patients. Addition of adjuvant chemotherapy to surgery has been shown to marginally improve the overall outcome. 11,16 However, in the study by Pawarode et al. the survival in the adjuvant-chemotherapy group was poorer than the surgery-only group. 7 This is possibly due to selection bias, as this was not a randomized controlled study. Patients who received adjuvant therapy had more advanced disease than those treated with resection alone. Chemoembolization with combination of materials such as gelfoam, and chemotherapeutic agents, induces tumour necrosis and delivers the drug locally. 17 The addition of lipidiol allows better targeting of the tumour tissue. 18 When chemoembolization is used alone, there is an objective reduction in tumour size, but the survival is unaltered. 19 However, chemoembolization is effective as an adjunctive therapy to resection or transplantation if it induces tumour necrosis. 20 In the study by Pawarode et al., chemoembolization was used alone, and the treated group had better survival than the untreated group. This conclusion is not valid as the study was not designed to compare the efficacy of different treatment modalities. One of the best options for therapy for patients with HCC is liver transplantation. This not only removes the tumour and the site for future HCC; it also replaces a diseased liver. The best result obtained for tumours less than 5 cm in size in patients with tumour node metastasis (TNM) stage I or II is 85% 4-year survival. 21,22 The problems associated with transplantation are organ scarcity, need for an established programme, cost, antirejection medication, and considerable perioperative morbidity and mortality. Moreover, recent studies comparing transplantation and surgical resection by an intention to treat analysis, found that resection offers better results, especially if the waiting period for transplantation is more than 6 months. 23 Cryoablation is useful for tumours which are not amenable to resection. Repeated freeze–thaw cycles at −198°C, delivered through a cryoprobe, destroy tumours up to 6 cm in diameter. 11,24 The 1- and 5-year survival among patients with tumours ≤ 5 cm is 93% and 51%, respectively. 25 Microwave coagulation therapy with a percutaneously placed needle electrode is useful in destroying small tumours and combining this therapy with simultaneous temporary interruption of blood supply yields better results. 26 The risk of thrombosis precludes the use of this method for tumours near blood vessels. Recently, radiofrequency ablation has been found to be safer and more effective than cryoablation or microwave therapy. Through needle electrodes placed percutaneously, or at the time of surgery, complete coagulative necrosis is achieved in situ in 80% of the cases. 27,28 Alcohol or acetic acid injection therapy is just as effective as surgical resection in small HCC. 29,30 It is especially useful among patients with decompensated liver disease who would not tolerate surgery. Proton beam irradiation has been found to be a safe and effective mode of therapy in patients with unresectable HCC and has 80–90% efficacy of tumour control. As the beam can be accurately targeted onto the tumorous tissue, the injury to the surrounding liver parenchyma is minimal. 31 The role of chemotherapy (systemic or intra-arterial) is limited, as hepatoma cells are quite often resistant to these drugs. 10 Doxorubicin alone is of little value. However, combination therapies, which include cisplatinum, 5-fluorouracil, mitomycin C, fluorodeoxuridine, seem to have some effect. 10 High doses of interferon-α reduces the tumour volume, however, there is no survival benefit. 32 Thus, for patients with small tumours (< 5 cm), the best treatment option, liver function permitting, is surgical resection. 33 Larger tumours in the absence of underlying liver disease can be tackled by surgical resection, preferably with preoperative chemoembolization or postoperative chemotherapy. For those with small tumours (< 5 cm) without portal vein invasion, liver transplantation is the most effective mode of therapy, especially if the liver function is poor. Whenever transplantation is not possible, various forms of local ablative therapies, like alcohol or acetic acid injection, chemoembolization, cryosurgery, radiofrequency ablation or microwave therapy can be tried. For those with large, unresectable tumours and poor liver function, the treatment options are limited to cryosurgery, chemoembolization, proton beam irradiation and chemotherapy. 33 The authors have not commented on the HCC stages of the patients in each treatment group. Patients receiving different modes of therapy are not comparable unless they are evaluated in a prospective, randomized, controlled trial. Thus, the survival data of various subgroups are not comparable. Moreover, it would be inappropriate to compare the treated and the untreated, as these again were not matched with respect to the stage of the disease. Also, the patients who were not offered treatment were those with tumours at an advanced stage, whose prognosis was inevitably poorer than those who were treated. Underlying liver function plays an important role in the prognosis of a patient with HCC. 11 In the study by Pawarode et al., patient death occurred more often, due to deteriorating liver function or portal hypertension (42%), rather than due to the tumour itself (36%). 7 The Okuda staging system which incorporates liver functional status in the staging system is thus more useful in predicting patient outcome. 34 Also, Pawarode et al., found that the Okuda staging system was an independent prognostic factor. 7 It is understandable that patients with multiple lesions and lymph node metastasis had a poorer outcome. However, it may be inappropriate to assess ‘treatment’ as a prognostic factor for the reasons mentioned. In conclusion, the most effective modalities for treating HCC, if feasible, are resection and transplantation. Ideally, to improve the overall outcome for a particular patient, combinations of various modalities of proven benefit should be used. However, the most effective way to decrease HCC-related morbidity and mortality, is to detect small HCC by screening the population at risk and to prevent hepatitis B and C infection." @default.
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• W2034654528 title "Treatment of hepatocellular carcinoma" @default.
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