Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma ≤4 cm
2004; Elsevier BV; Volume: 127; Issue: 6 Linguagem: Inglês
10.1053/j.gastro.2004.09.003
ISSN1528-0012
AutoresShi‐Ming Lin, Chun‐Jung Lin, Chen‐Chun Lin, Chao‐Wei Hsu, Yi‐Cheng Chen,
Tópico(s)Ovarian cancer diagnosis and treatment
ResumoBackground & Aims: The aim of this study was to compare the clinical outcome of percutaneous radiofrequency (RF) ablation, conventional percutaneous ethanol injection (PEI), and higher-dose PEI in treating hepatocellular carcinoma (HCC) 4 cm or less. Methods: A total of 157 patients with 186 HCCs 4 cm or less were randomly assigned to 3 groups (52 patients in the conventional PEI group, 53 in the higher-dose PEI group, and 52 in the RF group). Clinical outcomes in terms of complete tumor necrosis, overall survival, local tumor progression, additional new tumors, and cancer-free survival were compared across 3 groups. Results: The rate of complete tumor necrosis was 88% in the conventional PEI group, 92% in the higher-dose PEI group, and 96% in the RF group. Significantly fewer sessions were required to achieve complete tumor necrosis in the RF group than in the other 2 groups (P < .01). The local tumor progression rate was lowest in the RF group (vs the conventional PEI group, P = .012; vs the higher-dose PEI group, P = .037). The overall survival rate was highest in the RF group (vs the conventional PEI group, P = .014; vs the higher-dose PEI group, P = .023). The cancer-free survival rate was highest in the RF group (vs the conventional PEI group, P = .019; vs the higher-dose PEI group, P = .024). Multivariate analysis determined that tumor size, tumor differentiation, and the method of treatment (RF vs both methods of PEI) were significant factors in relation to local tumor progression, overall survival, and cancer-free survival. Conclusions: The results show that RF ablation yielded better clinical outcomes than conventional and higher-dose PEI in treating HCC 4 cm or less. Background & Aims: The aim of this study was to compare the clinical outcome of percutaneous radiofrequency (RF) ablation, conventional percutaneous ethanol injection (PEI), and higher-dose PEI in treating hepatocellular carcinoma (HCC) 4 cm or less. Methods: A total of 157 patients with 186 HCCs 4 cm or less were randomly assigned to 3 groups (52 patients in the conventional PEI group, 53 in the higher-dose PEI group, and 52 in the RF group). Clinical outcomes in terms of complete tumor necrosis, overall survival, local tumor progression, additional new tumors, and cancer-free survival were compared across 3 groups. Results: The rate of complete tumor necrosis was 88% in the conventional PEI group, 92% in the higher-dose PEI group, and 96% in the RF group. Significantly fewer sessions were required to achieve complete tumor necrosis in the RF group than in the other 2 groups (P < .01). The local tumor progression rate was lowest in the RF group (vs the conventional PEI group, P = .012; vs the higher-dose PEI group, P = .037). The overall survival rate was highest in the RF group (vs the conventional PEI group, P = .014; vs the higher-dose PEI group, P = .023). The cancer-free survival rate was highest in the RF group (vs the conventional PEI group, P = .019; vs the higher-dose PEI group, P = .024). Multivariate analysis determined that tumor size, tumor differentiation, and the method of treatment (RF vs both methods of PEI) were significant factors in relation to local tumor progression, overall survival, and cancer-free survival. Conclusions: The results show that RF ablation yielded better clinical outcomes than conventional and higher-dose PEI in treating HCC 4 cm or less. Surveillance with ultrasonography (US) and α-fetoprotein level can be used for early detection of small hepatocellular carcinomas (HCCs).1Liaw Y.F. Tai D.Y. Chu C.M. Lin D.Y. Sheen I.S. Chen T.J. Pao C.C. Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. A prospective study.Gastroenterology. 1986; 90: 263-267Abstract PubMed Google Scholar Various treatment options are available. Surgical resection may be effective in selected patients with a single small tumor, but fewer than 20% of patients are candidates for surgery.2Makuuchi M. Kosuge T. Takayama T. Yamazaki S. Kakazu T. Miyagawa S. Kawasaki S. Surgery for small liver cancers.Semin Surg Oncol. 1993; 9: 298-304Crossref PubMed Scopus (676) Google Scholar, 3Livraghi T. Makuuchi M. Buscarini L. Therapeutic guidelines.in: Livraghi T Makuuchi M Buscarini L Diagnosis and treatment of hepatocellular carcinoma. Greenwich Medical Media, London1997: 413-424Google Scholar As a result, various local therapies have been proposed and accepted as possible modalities for treating patients with HCC.2Makuuchi M. Kosuge T. Takayama T. Yamazaki S. Kakazu T. Miyagawa S. Kawasaki S. Surgery for small liver cancers.Semin Surg Oncol. 1993; 9: 298-304Crossref PubMed Scopus (676) Google Scholar, 3Livraghi T. Makuuchi M. Buscarini L. Therapeutic guidelines.in: Livraghi T Makuuchi M Buscarini L Diagnosis and treatment of hepatocellular carcinoma. Greenwich Medical Media, London1997: 413-424Google Scholar, 4Castells A. Bruix J. Bru C. Fuster J. Vilana R. Navasa M. Ayuso C. Boix L. Visa J. Rodes J. Treatment of small hepatocellular carcinoma in cirrhotic patients a cohort study comparing surgical resection and percutaneous ethanol injection.Hepatology. 1993; 18: 1121-1126PubMed Google Scholar, 5Arii S. Yamaoka Y. Futagawa S. Inoue K. Kobayashi K. Kojiro M. Makuuchi M. Nakamura Y. Okita K. Yamada R. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinoma a retrospective and nation wide survey in Japan. The Liver Cancer Study Group of Japan.Hepatology. 2000; 32: 1224-1229Crossref PubMed Scopus (707) Google Scholar, 6Shiina S. Tagawa K. Niwa Y. Unuma T. Komatsu Y. Yoshiura K. Hamada E. Takahashi M. Shiratori Y. Yerano A. Omata M. Percutaneous ethanol injection therapy for hepatocellular carcinoma in 146 patients.Am J Roentgenol. 1993; 160: 1023-1028Crossref PubMed Scopus (374) Google Scholar, 7Livraghi T. Giorgio A. Mann G. Salmi A. de Sio I. Bolondi L. Pompili M. Brunello F. Lazzaroni S. Torzilli G. Zucchi A. Hepatocellular carcinoma and cirrhosis in 746 patients long-term results of percutaneous ethanol injection.Radiology. 1995; 197: 101-108PubMed Google Scholar Among various local ablative modalities, percutaneous ethanol injection (PEI) is considered the most easily performed and effective modality of direct ablation therapy for HCC.2Makuuchi M. Kosuge T. Takayama T. Yamazaki S. Kakazu T. Miyagawa S. Kawasaki S. Surgery for small liver cancers.Semin Surg Oncol. 1993; 9: 298-304Crossref PubMed Scopus (676) Google Scholar, 3Livraghi T. Makuuchi M. Buscarini L. Therapeutic guidelines.in: Livraghi T Makuuchi M Buscarini L Diagnosis and treatment of hepatocellular carcinoma. Greenwich Medical Media, London1997: 413-424Google Scholar, 4Castells A. Bruix J. Bru C. Fuster J. Vilana R. Navasa M. Ayuso C. Boix L. Visa J. Rodes J. Treatment of small hepatocellular carcinoma in cirrhotic patients a cohort study comparing surgical resection and percutaneous ethanol injection.Hepatology. 1993; 18: 1121-1126PubMed Google Scholar, 5Arii S. Yamaoka Y. Futagawa S. Inoue K. Kobayashi K. Kojiro M. Makuuchi M. Nakamura Y. Okita K. Yamada R. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinoma a retrospective and nation wide survey in Japan. The Liver Cancer Study Group of Japan.Hepatology. 2000; 32: 1224-1229Crossref PubMed Scopus (707) Google Scholar, 6Shiina S. Tagawa K. Niwa Y. Unuma T. Komatsu Y. Yoshiura K. Hamada E. Takahashi M. Shiratori Y. Yerano A. Omata M. Percutaneous ethanol injection therapy for hepatocellular carcinoma in 146 patients.Am J Roentgenol. 1993; 160: 1023-1028Crossref PubMed Scopus (374) Google Scholar, 7Livraghi T. Giorgio A. Mann G. Salmi A. de Sio I. Bolondi L. Pompili M. Brunello F. Lazzaroni S. Torzilli G. Zucchi A. Hepatocellular carcinoma and cirrhosis in 746 patients long-term results of percutaneous ethanol injection.Radiology. 1995; 197: 101-108PubMed Google Scholar Radiofrequency (RF) ablation is being considered as an effective therapy for HCC.8Livraghi T. Goldberg S.N. Lazzaroni S. Meloni F. Solbiati L. Gazelle G.S. Small hepatocellular carcinoma treatment with radio-frequency ablation versus ethanol injection.Radiology. 1999; 210: 655-661Crossref PubMed Scopus (1194) Google Scholar, 9Lencioni R.A. Aligaier H.P. Cioni D. Oischewski M. Deibert P. Crocetti L. Frings H. Laubenberger J. Zuber I. Blum H.E. Bartolozzi C. Small hepatocellular carcinoma in cirrhosis randomized comparison of radiofrequency thermal ablation versus percutaneous ethanol injection.Radiology. 2003; 228: 235-240Crossref PubMed Scopus (880) Google Scholar, 10McGahan J.P. Dodd G.D. Radiofrequency ablation of the liver current status.Am J Roentgenol. 2001; 176: 3-16Crossref PubMed Scopus (576) Google Scholar Additionally, RF ablation has been reported to be superior to conventional PEI because of a slightly higher rate of complete tumor necrosis (RF vs conventional PEI, 90% vs 80%), the need for fewer treatment sessions (RF vs conventional PEI, 1.2 vs 4.8) in HCC ≤3 cm,8Livraghi T. Goldberg S.N. Lazzaroni S. Meloni F. Solbiati L. Gazelle G.S. Small hepatocellular carcinoma treatment with radio-frequency ablation versus ethanol injection.Radiology. 1999; 210: 655-661Crossref PubMed Scopus (1194) Google Scholar and a significantly higher local recurrence-free survival in HCC ≤5 cm.9Lencioni R.A. Aligaier H.P. Cioni D. Oischewski M. Deibert P. Crocetti L. Frings H. Laubenberger J. Zuber I. Blum H.E. Bartolozzi C. Small hepatocellular carcinoma in cirrhosis randomized comparison of radiofrequency thermal ablation versus percutaneous ethanol injection.Radiology. 2003; 228: 235-240Crossref PubMed Scopus (880) Google Scholar However, conventional PEI may yield a more than 90% rate of complete necrosis in other reports, including HCC ≤3 cm or ≤5 cm.2Makuuchi M. Kosuge T. Takayama T. Yamazaki S. Kakazu T. Miyagawa S. Kawasaki S. Surgery for small liver cancers.Semin Surg Oncol. 1993; 9: 298-304Crossref PubMed Scopus (676) Google Scholar, 3Livraghi T. Makuuchi M. Buscarini L. Therapeutic guidelines.in: Livraghi T Makuuchi M Buscarini L Diagnosis and treatment of hepatocellular carcinoma. Greenwich Medical Media, London1997: 413-424Google Scholar, 4Castells A. Bruix J. Bru C. Fuster J. Vilana R. Navasa M. Ayuso C. Boix L. Visa J. Rodes J. Treatment of small hepatocellular carcinoma in cirrhotic patients a cohort study comparing surgical resection and percutaneous ethanol injection.Hepatology. 1993; 18: 1121-1126PubMed Google Scholar, 5Arii S. Yamaoka Y. Futagawa S. Inoue K. Kobayashi K. Kojiro M. Makuuchi M. Nakamura Y. Okita K. Yamada R. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinoma a retrospective and nation wide survey in Japan. The Liver Cancer Study Group of Japan.Hepatology. 2000; 32: 1224-1229Crossref PubMed Scopus (707) Google Scholar, 6Shiina S. Tagawa K. Niwa Y. Unuma T. Komatsu Y. Yoshiura K. Hamada E. Takahashi M. Shiratori Y. Yerano A. Omata M. Percutaneous ethanol injection therapy for hepatocellular carcinoma in 146 patients.Am J Roentgenol. 1993; 160: 1023-1028Crossref PubMed Scopus (374) Google Scholar, 7Livraghi T. Giorgio A. Mann G. Salmi A. de Sio I. Bolondi L. Pompili M. Brunello F. Lazzaroni S. Torzilli G. Zucchi A. Hepatocellular carcinoma and cirrhosis in 746 patients long-term results of percutaneous ethanol injection.Radiology. 1995; 197: 101-108PubMed Google Scholar, 9Lencioni R.A. Aligaier H.P. Cioni D. Oischewski M. Deibert P. Crocetti L. Frings H. Laubenberger J. Zuber I. Blum H.E. Bartolozzi C. Small hepatocellular carcinoma in cirrhosis randomized comparison of radiofrequency thermal ablation versus percutaneous ethanol injection.Radiology. 2003; 228: 235-240Crossref PubMed Scopus (880) Google Scholar Given HCC >3 cm, the effectiveness of conventional PEI monotherapy is assumed to be less satisfactory owing to limited spread of ethanol.11Livraghi T. Festi D. Monti F. Salmi A. Vettori C. US-guided percutaneous alcohol injection of small hepatic and abdominal tumors.Radiology. 1986; 161: 309-312PubMed Google Scholar, 12Vilana R. Bruix J. Bru C. Ayuso S. Sole M. Rodes J. Tumor size determines the efficacy of percutaneous ethanol injection for the treatment of small hepatocellular carcinoma.Hepatology. 1992; 16: 353-357Crossref PubMed Scopus (266) Google Scholar To solve this problem, Livraghi et al injected a large volume of ethanol in HCC >5 cm in a single session under general anesthesia,13Livraghi T. Lazzaroni S. Pellicano S. Ravasi S. Torzilli G. Vettori C. Percutaneous ethanol injection of hepatic tumors single session therapy with general anesthesia.Am J Roentgenol. 1994; 161: 1065-1069Crossref Scopus (118) Google Scholar whereas Shiina et al injected higher-dose ethanol into various parts of the tumor by inserting 3 needles in HCC >3 cm to enable the ethanol to distribute throughout the lesion rapidly.14Shiina S. Hata Y. Niwa Y. Komatsu Y. Tanaka T. Yoshiura K. Hamada E. OhShima M. Mutoh H. Kurita M. Multiple-needle insertion method in percutaneous ethanol injection therapy for liver neoplasms.Gastroenterol Jpn. 1991; 26: 47-50PubMed Google Scholar Therefore, if the clinician can perform PEI with high-dose ethanol via simultaneous multiple needle injection, its effect may be higher and require fewer sessions. Like the limited effect of conventional PEI for HCC with dimensions of 3–5 cm, RF ablation also achieved a lower rate of complete necrosis compared with the effect yielded in HCC ≤3 cm (HCC ≤3 cm vs >3 cm, 90% vs 71%).8Livraghi T. Goldberg S.N. Lazzaroni S. Meloni F. Solbiati L. Gazelle G.S. Small hepatocellular carcinoma treatment with radio-frequency ablation versus ethanol injection.Radiology. 1999; 210: 655-661Crossref PubMed Scopus (1194) Google Scholar, 15Livraghi T. Goldberg S.N. Lazzaroni S. Meloni F. Ierace T. Solbiati L. Gazelle G.S. Hepatocellular carcinoma radio-frequency ablation of medium and large lesions.Radiology. 2000; 214: 761-768Crossref PubMed Scopus (967) Google Scholar Therefore, the comparative effectiveness of conventional PEI, higher-dose PEI, and RF ablation in HCC measuring 3–5 cm remains uncertain and randomized controlled studies are lacking, although HCC ≤5 cm was generally accepted as the indicator of the level for both conventional PEI and RF ablation.2Makuuchi M. Kosuge T. Takayama T. Yamazaki S. Kakazu T. Miyagawa S. Kawasaki S. Surgery for small liver cancers.Semin Surg Oncol. 1993; 9: 298-304Crossref PubMed Scopus (676) Google Scholar, 3Livraghi T. Makuuchi M. Buscarini L. Therapeutic guidelines.in: Livraghi T Makuuchi M Buscarini L Diagnosis and treatment of hepatocellular carcinoma. Greenwich Medical Media, London1997: 413-424Google Scholar, 4Castells A. Bruix J. Bru C. Fuster J. Vilana R. Navasa M. Ayuso C. Boix L. Visa J. Rodes J. Treatment of small hepatocellular carcinoma in cirrhotic patients a cohort study comparing surgical resection and percutaneous ethanol injection.Hepatology. 1993; 18: 1121-1126PubMed Google Scholar, 5Arii S. Yamaoka Y. Futagawa S. Inoue K. Kobayashi K. Kojiro M. Makuuchi M. Nakamura Y. Okita K. Yamada R. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinoma a retrospective and nation wide survey in Japan. The Liver Cancer Study Group of Japan.Hepatology. 2000; 32: 1224-1229Crossref PubMed Scopus (707) Google Scholar, 6Shiina S. Tagawa K. Niwa Y. Unuma T. Komatsu Y. Yoshiura K. Hamada E. Takahashi M. Shiratori Y. Yerano A. Omata M. Percutaneous ethanol injection therapy for hepatocellular carcinoma in 146 patients.Am J Roentgenol. 1993; 160: 1023-1028Crossref PubMed Scopus (374) Google Scholar, 7Livraghi T. Giorgio A. Mann G. Salmi A. de Sio I. Bolondi L. Pompili M. Brunello F. Lazzaroni S. Torzilli G. Zucchi A. Hepatocellular carcinoma and cirrhosis in 746 patients long-term results of percutaneous ethanol injection.Radiology. 1995; 197: 101-108PubMed Google Scholar, 8Livraghi T. Goldberg S.N. Lazzaroni S. Meloni F. Solbiati L. Gazelle G.S. Small hepatocellular carcinoma treatment with radio-frequency ablation versus ethanol injection.Radiology. 1999; 210: 655-661Crossref PubMed Scopus (1194) Google Scholar, 9Lencioni R.A. Aligaier H.P. Cioni D. Oischewski M. Deibert P. Crocetti L. Frings H. Laubenberger J. Zuber I. Blum H.E. Bartolozzi C. Small hepatocellular carcinoma in cirrhosis randomized comparison of radiofrequency thermal ablation versus percutaneous ethanol injection.Radiology. 2003; 228: 235-240Crossref PubMed Scopus (880) Google Scholar, 10McGahan J.P. Dodd G.D. Radiofrequency ablation of the liver current status.Am J Roentgenol. 2001; 176: 3-16Crossref PubMed Scopus (576) Google Scholar, 11Livraghi T. Festi D. Monti F. Salmi A. Vettori C. US-guided percutaneous alcohol injection of small hepatic and abdominal tumors.Radiology. 1986; 161: 309-312PubMed Google Scholar, 12Vilana R. Bruix J. Bru C. Ayuso S. Sole M. Rodes J. Tumor size determines the efficacy of percutaneous ethanol injection for the treatment of small hepatocellular carcinoma.Hepatology. 1992; 16: 353-357Crossref PubMed Scopus (266) Google Scholar, 14Shiina S. Hata Y. Niwa Y. Komatsu Y. Tanaka T. Yoshiura K. Hamada E. OhShima M. Mutoh H. Kurita M. Multiple-needle insertion method in percutaneous ethanol injection therapy for liver neoplasms.Gastroenterol Jpn. 1991; 26: 47-50PubMed Google Scholar, 15Livraghi T. Goldberg S.N. Lazzaroni S. Meloni F. Ierace T. Solbiati L. Gazelle G.S. Hepatocellular carcinoma radio-frequency ablation of medium and large lesions.Radiology. 2000; 214: 761-768Crossref PubMed Scopus (967) Google Scholar, 16Lin S.M. Lin D.Y. Lin C.J. Percutaneous ethanol injection therapy in 47 cirrhotic patients with hepatocellular carcinoma 5 cm or less a long-term result.Int J Clin Pract. 1999; 53: 257-262PubMed Google Scholar, 17Curley S.A. Izzo F. Delrio P. Ellis L.M. Granchi J. Vallone P. Fiore F. Pignata S. Daniele B. Cremona F. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies results in 123 patients.Ann Surg. 1999; 230: 1-8Crossref PubMed Scopus (1024) Google Scholar, 18Ikeda M. Okada S. Ueno H. Okusaka T. Kuriyama H. Radiofrequency ablation and percutaneous ethanol injection in patients with small hepatocellular carcinoma a comparative study.Jpn J Clin Oncol. 2001; 31: 297-298Crossref PubMed Scopus (5) Google Scholar, 19Lin S.M. Lin C.J. Chung H.J. Hsu C.W. Peng C.Y. Power rolloff during interactive radiofrequency ablation can enhance necrosis when treating hepatocellular carcinoma.Am J Roentgenol. 2003; 180: 151-157Crossref PubMed Scopus (25) Google Scholar To our knowledge, recently there has been only one randomized study comparing RF ablation and conventional PEI in HCC ≤5 cm.9Lencioni R.A. Aligaier H.P. Cioni D. Oischewski M. Deibert P. Crocetti L. Frings H. Laubenberger J. Zuber I. Blum H.E. Bartolozzi C. Small hepatocellular carcinoma in cirrhosis randomized comparison of radiofrequency thermal ablation versus percutaneous ethanol injection.Radiology. 2003; 228: 235-240Crossref PubMed Scopus (880) Google Scholar Moreover, that study did not report any further stratification of tumor size in relation to the outcome.9Lencioni R.A. Aligaier H.P. Cioni D. Oischewski M. Deibert P. Crocetti L. Frings H. Laubenberger J. Zuber I. Blum H.E. Bartolozzi C. Small hepatocellular carcinoma in cirrhosis randomized comparison of radiofrequency thermal ablation versus percutaneous ethanol injection.Radiology. 2003; 228: 235-240Crossref PubMed Scopus (880) Google Scholar Therefore, we conducted a randomized controlled trial comparing the clinical outcomes among RF ablation and PEI with conventional and higher-dose ethanol injection per session in treating HCC ≤4 cm and conducted an extensive analysis that stratified tumor size in relation to outcome. The study was conducted with the approval of the institutional ethics board. Written informed consent was obtained from each patient and family member. At the time this study was designed, only a LeVeen RF needle 3.5 cm in diameter was available in our institute. In addition, successful ablation of an HCC tumor >3 cm was assumed to be difficult by conventional PEI alone,11Livraghi T. Festi D. Monti F. Salmi A. Vettori C. US-guided percutaneous alcohol injection of small hepatic and abdominal tumors.Radiology. 1986; 161: 309-312PubMed Google Scholar, 12Vilana R. Bruix J. Bru C. Ayuso S. Sole M. Rodes J. Tumor size determines the efficacy of percutaneous ethanol injection for the treatment of small hepatocellular carcinoma.Hepatology. 1992; 16: 353-357Crossref PubMed Scopus (266) Google Scholar but successful ablation has been achieved in up to 69 (95%) of 73 HCC ≤5 cm.9Lencioni R.A. Aligaier H.P. Cioni D. Oischewski M. Deibert P. Crocetti L. Frings H. Laubenberger J. Zuber I. Blum H.E. Bartolozzi C. Small hepatocellular carcinoma in cirrhosis randomized comparison of radiofrequency thermal ablation versus percutaneous ethanol injection.Radiology. 2003; 228: 235-240Crossref PubMed Scopus (880) Google Scholar RF ablation also was less satisfactory for HCC >3 cm, reported as successful ablation in 36 (71%) of 51 HCC measuring 3.1–5 cm in diameter.15Livraghi T. Goldberg S.N. Lazzaroni S. Meloni F. Ierace T. Solbiati L. Gazelle G.S. Hepatocellular carcinoma radio-frequency ablation of medium and large lesions.Radiology. 2000; 214: 761-768Crossref PubMed Scopus (967) Google Scholar Therefore, we selected HCC ≤4 cm for this study because these 3 treatments are readily comparable for this group. In addition, at the time of the planning of this study, a local recurrence rate after PEI was reported to be 10.5%–26%6Shiina S. Tagawa K. Niwa Y. Unuma T. Komatsu Y. Yoshiura K. Hamada E. Takahashi M. Shiratori Y. Yerano A. Omata M. Percutaneous ethanol injection therapy for hepatocellular carcinoma in 146 patients.Am J Roentgenol. 1993; 160: 1023-1028Crossref PubMed Scopus (374) Google Scholar, 7Livraghi T. Giorgio A. Mann G. Salmi A. de Sio I. Bolondi L. Pompili M. Brunello F. Lazzaroni S. Torzilli G. Zucchi A. Hepatocellular carcinoma and cirrhosis in 746 patients long-term results of percutaneous ethanol injection.Radiology. 1995; 197: 101-108PubMed Google Scholar, 16Lin S.M. Lin D.Y. Lin C.J. Percutaneous ethanol injection therapy in 47 cirrhotic patients with hepatocellular carcinoma 5 cm or less a long-term result.Int J Clin Pract. 1999; 53: 257-262PubMed Google Scholar and RF ablation to be 3.6%–15%.17Curley S.A. Izzo F. Delrio P. Ellis L.M. Granchi J. Vallone P. Fiore F. Pignata S. Daniele B. Cremona F. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies results in 123 patients.Ann Surg. 1999; 230: 1-8Crossref PubMed Scopus (1024) Google Scholar, 18Ikeda M. Okada S. Ueno H. Okusaka T. Kuriyama H. Radiofrequency ablation and percutaneous ethanol injection in patients with small hepatocellular carcinoma a comparative study.Jpn J Clin Oncol. 2001; 31: 297-298Crossref PubMed Scopus (5) Google Scholar Based on the assumption that a local HCC recurrence rate would be 20% or more in the PEI group, we calculated that about 50 patients would be required in each group to achieve a power of .80 and a significant level of .05 in assessing the difference across the 3 groups. Starting in April 2000, we conducted a randomized controlled trial comparing RF ablation and PEI for the treatment of cirrhotic patients with 1–3 pathology or cytology-proven HCCs for each tumor measuring 1–4 cm in greatest dimension. The primary end point of the study was local tumor progression. Secondary end points were overall survival and cancer-free survival. The exclusion criteria were patients with Child–Pugh grade C, previous HCC treatment, and the tumor located within 5 mm of liver hila or the common bile duct, owing to the risk of injury to the major bile duct following RF ablation. Between April 2000 and April 2002, 157 patients were randomly allocated to 3 groups: 52 in the conventional PEI group, 53 in the higher-dose PEI group, and 52 in the RF group. Of these, 6 patients in the conventional PEI group, 3 patients in the higher-dose PEI group, and 2 patients in the RF group did not receive a complete course of treatment or did not achieve complete tumor necrosis following 2 courses of therapy8Livraghi T. Goldberg S.N. Lazzaroni S. Meloni F. Solbiati L. Gazelle G.S. Small hepatocellular carcinoma treatment with radio-frequency ablation versus ethanol injection.Radiology. 1999; 210: 655-661Crossref PubMed Scopus (1194) Google Scholar, 9Lencioni R.A. Aligaier H.P. Cioni D. Oischewski M. Deibert P. Crocetti L. Frings H. Laubenberger J. Zuber I. Blum H.E. Bartolozzi C. Small hepatocellular carcinoma in cirrhosis randomized comparison of radiofrequency thermal ablation versus percutaneous ethanol injection.Radiology. 2003; 228: 235-240Crossref PubMed Scopus (880) Google Scholar, 12Vilana R. Bruix J. Bru C. Ayuso S. Sole M. Rodes J. Tumor size determines the efficacy of percutaneous ethanol injection for the treatment of small hepatocellular carcinoma.Hepatology. 1992; 16: 353-357Crossref PubMed Scopus (266) Google Scholar and all of them underwent transarterial chemoembolization. The randomization of the treatment was according to the computer-generated randomization list that was not available to the treating physician. Tumor diameters were determined as the largest dimension measured by US. The numbers of tumors were determined by US, artery angiography, and computed tomography (CT) during arterioportography. Routine color Doppler US was used to detect the vascular invasion and any vessel surrounding the target tumor. The 3 groups exhibited no significant differences in respect to all clinical parameters (Table 1).Table 1Clinical Characteristics in the RF Ablation, Conventional PEI, and Higher-Dose PEI GroupsCharacteristicsRF ablationConventional PEIHigher-dose PEINo. of patients525253Age (y)aMean ± SD.62 ± 1159 ± 1061 ± 12Male/female ratiobData are expressed as numbers (%).35 (67)/17 (33)34 (65)/18 (35)36 (70)/17 (30)Child–Pugh class: A/BbData are expressed as numbers (%).41 (79)/11 (21)39 (75)/12 (25)39 (74)/14 (26)Underlying liver disease: HBV/HCV/othersbData are expressed as numbers (%).35/16/1 (67/31/2)37/14/1 (71/27/2)37/16/1 (69/30/1)No. of tumors: 1/2/3bData are expressed as numbers (%).38/11/3 (73/21/6)40/9/3 (77/17/6)41/10/2 (77/19/4)Ratio of tumor of 1–2/2.1–3/3.1–4 cmbData are expressed as numbers (%).14/23/15 (27/44/29)16/22/14 (31/42/27)17/22/14 (32/42/26)Size of main tumor (cm)aMean ± SD.2.9 ± .82.8 ± .82.8 ± .9Edmondson’s grade of tumor: I or II/III or IVbData are expressed as numbers (%).39 (57)/30 (43)39 (58)/28 (42)40 (60)/27 (40)Baseline laboratory parameters AST (IU/L)aMean ± SD.79 ± 3081 ± 3491 ± 40 ALT (IU/L)aMean ± SD.72 ± 2676 ± 2779 ± 21 Albumin (g/dL)aMean ± SD.3.7 ± .83.8 ± 1.03.8 ± 1.1 Platelet count (×1000/mm3)aMean ± SD.8.4 ± 2.08.6 ± 2.18.8 ± 2.3 α-fetoprotein (ng/mL)bData are expressed as numbers (%). 4008 (15)9 (17)9 (17)Follow-up (mo)aMean ± SD.24.5 ± 11.323.8 ± 10.424.1 ± 0.7NOTE. There was no significant difference in each characteristic among the 3 groups by either the Student t test or χ2 test with Yates’ correction.AST, aspartate aminotransferase; ALT, alanine aminotransferase.a Mean ± SD.b Data are expressed as numbers (%). Open table in a new tab NOTE. There was no significant difference in each characteristic among the 3 groups by either the Student t test or χ2 test with Yates’ correction. AST, aspartate aminotransferase; ALT, alanine aminotransferase. Conventional liver biochemical tests, prothrombin time, and complete blood cell counts were measured before treatment. Three-phase helical CT was used to detect any enhancement of the tumor throughout the study period. The first session of conventional PEI was performed 1 day following CT arterioportography. Conventional PEI was performed at the outpatient clinic if there was no severe adverse effect after the first PEI during hospitalization.2Makuuchi M. Kosuge T. Takayama T. Yamazaki S. Kakazu T. Miyagawa S. Kawasaki S. Surgery for small liver cancers.Semin Surg Oncol. 1993; 9: 298-304Crossref PubMed Scopus (676) Google Scholar, 3Livraghi T. Makuuchi M. Buscarini L. Therapeutic guidelines.in: Livraghi T Makuuchi M Buscarini L Diagnosis and treatment of hepatocellular carcinoma. Greenwich Medical Media, London1997: 413-424Google Scholar, 4Castells A. Bruix J. Bru C. Fuster J. Vilana R. Navasa M. Ayuso C. Boix L. Visa J. Rodes J. Treatment of small hepatocellular carcinoma in cirrhotic patients a cohort study comparing surgical resection and percutaneous ethanol injection.Hepatology. 1993; 18: 1121-1126PubMed Google Scholar, 5Arii S. Yamaoka Y. Futagawa S. Inoue K. Kobayashi K. Kojiro M. Makuuchi M. Nakamura Y. Okita K. Yamada R. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinoma a retrospective and nation wide survey in Japan. 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