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236 Hepatic arterial 90yttrium microspheres therapy and follow-up in 102 patients with unresectable hepatocellular carcinoma (HCC)
Category 3: Liver Tumors (Epidemiology, Diagnosis, Management) AENs that disappear on two further MR studies are likely consistent with after:o-portal shunting within the cirrhotic liver and maybe followed by serial ultrasound.
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OCCULT HBV INFECTION IS ASSOCIATED WITH THE DEVELOPMENT OF HCC IN CHRONIC HEPATITIS PATIENTS
G. Squadrito, T. Pollicino, G. Cacc~uno. I. Cacciola, T. Resmccia, T. La Masa, G. Raimondo. Unit of Clinical and Molecular Hepatology.
University of Mess:ha, Mess:ha, Italy Occult HBV infection frequently occurs in patients with chronic liver disease, and much evidence suggests that it is significantly associated with cirrhosis and hepatocellular carcinoma (HCC). However, no follow-up study has been performed so far evaluating over time the risk of HCC development in chronic hepatitis patients with or without occult HBV infection. We considered tile cohort of file 380 patients with HBsAg negative chronic liver disease (326 positive and 54 negative for HCV) attending our unit from 1991 to 2000 and tested for occult HBV DNA by the analysis of their liver biopsy specimens. Tile patients with and those without occult HBV were, respectively, 133 (35%) and 247 (65%), and the most severe forms of liver disease were siguificanfly associated with oc~flt HBV infection (p = 0.001) in accordance with previous reports. No other demographic, clinical or virological difference was found between subjects with or without occult HBV One hundred thirty-four of these patients (124 positive and 10 negative for HCV infection) were followed up in our out patient Clinic for a minimum of 50 months (median time of 82.8±32.6 months). This group did not show any statistically significant difference with the 246 cases lost at the follow up. Fifty-three (39%) of these 134 patients had and 81 (61%) had not HBV-DNA sequences in tile liver. Nine cases developed HCC during the follow up, 8 with and 1 without occult HBV infection (p 0.001). This observational cohort study confirms that, among the HBsAg negative patients with chronic hepatitis, HCC mostly develops in carriers of occult HBV Therefore, tile evaluation of HBV genomes in chronic hepatitis patients appears to be a powerful tool for the identification of the individuals at higher risk o f HCC development.
[•6•
HEPATIC ARTERIAL 9°Y-ITRIUM MICROSPHERES T H E R A P Y AND FOLLOW-UP IN 102 PATIENTS WITH UNRESECTABLE HEPATOCELLULAR C A R C I N O M A (HCC)
B.I. Carr I , A.B. Zajko 2, J.L. Steel I . :Liver Cancer Center, USA,"
2Department of Radiology, USA Tile tumor responses, long-term survival and toxic:ties are reported for a large group of U.S. patients (pts) with unresectable, multifocal, and bilobar HCC, trested with 9°Yttrium microspheres (Therasphere). All pts had biopsy-proven HCC, a bilirubin of <2.5 mg/dl and no baseline metastases. 76% had cirrhosis; males :females 2:1, ages 21-86yrs. Results: 80 pts are available for follow-up >1 year. All are available for toxic:ties. 30% had PIL 50% had minor response or stable disease, and 20% progressed. Responses by CT provided an underestimate of actual benefit, since 80% ofpts had major decrease in tumor vascularity by Cq2 Survivals were: Okuda I: median=628 days; Okuda II: median 281 days; CLIP 0: median 812 days; CLIP 1-2: median 384 days; CLIP>2: median 194 days. 5 pts are alive >3 yr. Responders were heterogeneous with respect to size, vascularity or PV thrombosis. These results were remarkable since 70% of pts required only one treatment cycle ever, 30% had two cycles, and 5% ofpts had three treatment cycles. The mean liver dose of radiation actually delivered was 145 Gy, after a typical 5 or 10 GBq dose. Main clinical tuxicities were episodic nausea and abdominal pain and fatigue. Only 7 pts had post-embolization syndrome. There were essentially no myelo-toxicities. Bilirubin increased by 100-150% in 24%
91
ofpts, 150-200% in 15% ofpts, and >200% in 38% ofpts, of which half were transient. Remarkably, lymphocytes decreased in 90% of pts, often by >70% and lasted many months. There were no clinical consequences of this. Conclusions: 9°Yt.trium rnicrospheres (Therasphere) appears to represent a major new, relatively nontoxic treatment for advanced-stage HCC, which is the commonest presentation in the U.S.A.
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A C C U R A C Y OF HELICAL COMPUTED T O M O G R A P H Y FOR A S S E S S M E N T OF LOCAL RESPONSE OF HEPATOCARCINOMA AFTER PERCUTANEOUS ETHANOL INJECTION: A PROSPECTIVE STUDY USING THE EXPLANTED LIVER AS GOLD-STANDARD
J.F. Castroagud/n ~, C. Villalba 2, M.B. Delgado 1, S.M. Mart/nez I , I. Abdulkader 3, J. Forteza 3, M. Bustarnante I , J. Martlnez I , R. Conde I , F.R. Segade ~, E. Varo ~. :Liver Transplantation Unit, Spain, 2Department
of Radiology, Spain," 3Department of Pathology, Spain Background: Helical computed tomography (hCT) is considered file imaging technique of choice for assessment of local response of hepatocellular carcinoma (HCC) to percutaneous ethanol injection (PEI). Nevertheless, accuracy of hCT in comparison with the histepathologic analysis of liver has not been adequately evaluated. Aim: To evaluate the accuracy of hCT for assessment of local response of HCC to PEI. Methods: 33 patients (26 male, mean age 58.7±7.1 years) with HCC listed for liver transplantation (LT) were included. Etiology of cirrhoais was alcoholic in 12 patients, viral infection in 16, haemochromatosis in 2, and cryptegenic in 3 patients. Pre-treamaent Child-Pugh score was 6.5±1.7. CHC was single in 29 patients (87.9%). Tumor diameter was 31±12 mm. Basal AFP was 5.2±194ng/ml (range 1-1042). PEI was performed in 38 nodules, with a mean of 3±1.8 sessions and injected volume of 37.7±28.2 ml of ethanol by lesion, hCT was performed at 4th week after PEI, and every three months until LT. Scans were evaluated by a blind radiologist. Analysed variables inchlded number of lesions, diameter, and area of necrosis (%), defined as non-enhanced areas after injection of intravenous contrast. After LT, tile e'~planted liver was examinated throughout 0.5 can wide cross-sections by a blind pathologist. Local response was defined as percentage of necrosis respect to total diameter. Results: 15 patients (11 male, age 56.1±7.4 years) with 16 nodules of HCC finished tile period study. Tumor diameter observed by hCT was 31.6± 10.4 mm, with a mean necrosis of 77.5% (range 0-100%). Tumor diameter was 3 0 ± 1 2 . 8 m m in the explanted liver. Necrosis >90% was observed in 11 lesions, 50 90% in 3, and <50% in the remaining 2 lesions. Mean necrosis was 81.9% (range 30-100%). No differences between hCT and pathologic examination with respect to tumor diameter and percentage of necrosis were observed. Sensitivity, specificity, positive and negative predictive values o f h C T for assessment of complete response were 81.8%, 100%, 100% and 71.4%, respectively. Overall accuracy was 87.5%. Conclusions: hCT is an accurate imaging technique for the assessment of local response of HCC to PEI. In our series, an adequate correlation between hCT and pathologic findings was observed.
[•
OCCULT HBV INFECTION IS ASSOCIATED WITH THE DEVELOPMENT OF HCC IN CHRONIC HEPATITIS PATIENTS
G. Squadrito, T. Pollicino, G. Cacc~uno. I. Cacciola, T. Resmccia, T. La Masa, G. Raimondo. Unit of Clinical and Molecular Hepatology.
University of Mess:ha, Mess:ha, Italy Occult HBV infection frequently occurs in patients with chronic liver disease, and much evidence suggests that it is significantly associated with cirrhosis and hepatocellular carcinoma (HCC). However, no follow-up study has been performed so far evaluating over time the risk of HCC development in chronic hepatitis patients with or without occult HBV infection. We considered tile cohort of file 380 patients with HBsAg negative chronic liver disease (326 positive and 54 negative for HCV) attending our unit from 1991 to 2000 and tested for occult HBV DNA by the analysis of their liver biopsy specimens. Tile patients with and those without occult HBV were, respectively, 133 (35%) and 247 (65%), and the most severe forms of liver disease were siguificanfly associated with oc~flt HBV infection (p = 0.001) in accordance with previous reports. No other demographic, clinical or virological difference was found between subjects with or without occult HBV One hundred thirty-four of these patients (124 positive and 10 negative for HCV infection) were followed up in our out patient Clinic for a minimum of 50 months (median time of 82.8±32.6 months). This group did not show any statistically significant difference with the 246 cases lost at the follow up. Fifty-three (39%) of these 134 patients had and 81 (61%) had not HBV-DNA sequences in tile liver. Nine cases developed HCC during the follow up, 8 with and 1 without occult HBV infection (p 0.001). This observational cohort study confirms that, among the HBsAg negative patients with chronic hepatitis, HCC mostly develops in carriers of occult HBV Therefore, tile evaluation of HBV genomes in chronic hepatitis patients appears to be a powerful tool for the identification of the individuals at higher risk o f HCC development.
[•6•
HEPATIC ARTERIAL 9°Y-ITRIUM MICROSPHERES T H E R A P Y AND FOLLOW-UP IN 102 PATIENTS WITH UNRESECTABLE HEPATOCELLULAR C A R C I N O M A (HCC)
B.I. Carr I , A.B. Zajko 2, J.L. Steel I . :Liver Cancer Center, USA,"
2Department of Radiology, USA Tile tumor responses, long-term survival and toxic:ties are reported for a large group of U.S. patients (pts) with unresectable, multifocal, and bilobar HCC, trested with 9°Yttrium microspheres (Therasphere). All pts had biopsy-proven HCC, a bilirubin of <2.5 mg/dl and no baseline metastases. 76% had cirrhosis; males :females 2:1, ages 21-86yrs. Results: 80 pts are available for follow-up >1 year. All are available for toxic:ties. 30% had PIL 50% had minor response or stable disease, and 20% progressed. Responses by CT provided an underestimate of actual benefit, since 80% ofpts had major decrease in tumor vascularity by Cq2 Survivals were: Okuda I: median=628 days; Okuda II: median 281 days; CLIP 0: median 812 days; CLIP 1-2: median 384 days; CLIP>2: median 194 days. 5 pts are alive >3 yr. Responders were heterogeneous with respect to size, vascularity or PV thrombosis. These results were remarkable since 70% of pts required only one treatment cycle ever, 30% had two cycles, and 5% ofpts had three treatment cycles. The mean liver dose of radiation actually delivered was 145 Gy, after a typical 5 or 10 GBq dose. Main clinical tuxicities were episodic nausea and abdominal pain and fatigue. Only 7 pts had post-embolization syndrome. There were essentially no myelo-toxicities. Bilirubin increased by 100-150% in 24%
91
ofpts, 150-200% in 15% ofpts, and >200% in 38% ofpts, of which half were transient. Remarkably, lymphocytes decreased in 90% of pts, often by >70% and lasted many months. There were no clinical consequences of this. Conclusions: 9°Yt.trium rnicrospheres (Therasphere) appears to represent a major new, relatively nontoxic treatment for advanced-stage HCC, which is the commonest presentation in the U.S.A.
•
A C C U R A C Y OF HELICAL COMPUTED T O M O G R A P H Y FOR A S S E S S M E N T OF LOCAL RESPONSE OF HEPATOCARCINOMA AFTER PERCUTANEOUS ETHANOL INJECTION: A PROSPECTIVE STUDY USING THE EXPLANTED LIVER AS GOLD-STANDARD
J.F. Castroagud/n ~, C. Villalba 2, M.B. Delgado 1, S.M. Mart/nez I , I. Abdulkader 3, J. Forteza 3, M. Bustarnante I , J. Martlnez I , R. Conde I , F.R. Segade ~, E. Varo ~. :Liver Transplantation Unit, Spain, 2Department
of Radiology, Spain," 3Department of Pathology, Spain Background: Helical computed tomography (hCT) is considered file imaging technique of choice for assessment of local response of hepatocellular carcinoma (HCC) to percutaneous ethanol injection (PEI). Nevertheless, accuracy of hCT in comparison with the histepathologic analysis of liver has not been adequately evaluated. Aim: To evaluate the accuracy of hCT for assessment of local response of HCC to PEI. Methods: 33 patients (26 male, mean age 58.7±7.1 years) with HCC listed for liver transplantation (LT) were included. Etiology of cirrhoais was alcoholic in 12 patients, viral infection in 16, haemochromatosis in 2, and cryptegenic in 3 patients. Pre-treamaent Child-Pugh score was 6.5±1.7. CHC was single in 29 patients (87.9%). Tumor diameter was 31±12 mm. Basal AFP was 5.2±194ng/ml (range 1-1042). PEI was performed in 38 nodules, with a mean of 3±1.8 sessions and injected volume of 37.7±28.2 ml of ethanol by lesion, hCT was performed at 4th week after PEI, and every three months until LT. Scans were evaluated by a blind radiologist. Analysed variables inchlded number of lesions, diameter, and area of necrosis (%), defined as non-enhanced areas after injection of intravenous contrast. After LT, tile e'~planted liver was examinated throughout 0.5 can wide cross-sections by a blind pathologist. Local response was defined as percentage of necrosis respect to total diameter. Results: 15 patients (11 male, age 56.1±7.4 years) with 16 nodules of HCC finished tile period study. Tumor diameter observed by hCT was 31.6± 10.4 mm, with a mean necrosis of 77.5% (range 0-100%). Tumor diameter was 3 0 ± 1 2 . 8 m m in the explanted liver. Necrosis >90% was observed in 11 lesions, 50 90% in 3, and <50% in the remaining 2 lesions. Mean necrosis was 81.9% (range 30-100%). No differences between hCT and pathologic examination with respect to tumor diameter and percentage of necrosis were observed. Sensitivity, specificity, positive and negative predictive values o f h C T for assessment of complete response were 81.8%, 100%, 100% and 71.4%, respectively. Overall accuracy was 87.5%. Conclusions: hCT is an accurate imaging technique for the assessment of local response of HCC to PEI. In our series, an adequate correlation between hCT and pathologic findings was observed.