- Email: [email protected]
30 ROLE OF SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA IN THE BARCELONA-CLINIC-LIVER-CANCER CLASSIFICATION: A PROSPECTIVE STUDY
S14
Thursday, 24 April
29 NEITHER MULTIPLE TUMORS NOR PORTAL HYPERTENSION ARE OPERATIVE CONTRAINDICATIONS FOR HEPATOCELLULAR CARCINOMA T. Ishizawa, K. Hasegawa, T. Aoki, M. Takahashi, Y. Inoue, H. Imamura, Y. Sugawara, N. Kokudo, M. Makuuchi. Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan E-mail: [email protected] Background and Aims: The surgical indications for multiple hepatocellular carcinomas (HCCs) and for HCC with portal hypertension (PHT) remain controversial. Methods: We reviewed 434 patients who had undergone an initial resection for HCC and divided them into multiple (n = 126) and single (n = 308) groups according to the tumor number. We also classified 386 of them into PHT (n = 136) and no PHT (n = 250) groups, according to the definition of PHT (the presence of esophageal varices or platelet count <100,000/mL associated with splenomegaly). The indications for liver resection and operative procedures were determined according to the decision criteria based on the presence or absence of uncontrolled ascites, the serum bilirubin level, and the indocyanine green retention rate at 15 minutes. Results: Among Child-Pugh class A patients, the overall survival rates were satisfactory, even in the multiple group (58% at 5 years) and the PHT group (56%), although they were lower than those in the single (68%, P = 0.035) or the no PHT groups (71%, P = 0.008), respectively. The cumulative recurrence rates for Child-Pugh class A patients were higher in the multiple group (75% at 5 years) and the PHT group (75%) than those in the single (60%, P < 0.001) or the no PHT groups (58%, P = 0.008), respectively. Long-term results in Child-Pugh class B patients with multiple HCCs were unsatisfactory (the 5-year overall survival rate and cumulative recurrence rate were 19% and 100%, respectively). Multivariate analyses revealed that the presence of multiple tumors independently increased a risk of postoperative recurrence (relative risk, 1.64; 95% confidence interval, 1.23−2.18; P = 0.001). A second resection provided a satisfactory overall survival after the diagnosis of recurrence in the multiple (73% at 3 years) or PHT (73%) groups as well as in the single (79%) or no PHT (81%) groups. Conclusions: Resection can provide survival benefits even for patients with multiple tumors in a background of Child-Pugh class A cirrhosis as well as in those with PHT. 30 ROLE OF SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA IN THE BARCELONA-CLINIC-LIVER-CANCER CLASSIFICATION: A PROSPECTIVE STUDY M. Donadon, F. Procopio, D. Del Fabbro, F. Botea, A. Palmisano, M. Marconi, M. Montorsi, G. Torzilli. Third Department of Surgery, University of Milan, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy E-mail: [email protected] Background: For patients with multiple and/or with vascular invasive hepatocellular carcinoma (HCC) palliation is the only feasible approach according with the Barcelona-Clinic-Liver-Cancer classification (BCLC). However, some authors reported survival benefit after surgery even in more advanced patients. We prospectively evaluated the short- and longterm outcome of patients resected for HCC based on a selection process, in which the BCLC intermediate and advanced stages were not contraindicated. Methods: Patients wee selected for surgery based on presence-absence of ascites, serum bilirubin level and expected remnant liver volume. Esophageal varices were not a contraindication once eradicated endoscopically. Surgical strategy was based on the relationship between the tumor and the intrahepatic vascular structures at intraoperative ultrasonography
(IOUS). Mortality, morbidity, rate of cut-edge local recurrences, and longterm outcome were evaluated. A P value less than 0.05 was considered statistically significant. Results: One-hundred-fifty-two patients underwent surgery and 143 (94%) were resected: of them, 81 were BCLC stage 0-A, 34 B, and 28 C. The BCLC C stage was, in all patients, due to macroscopic vascular invasion. Hospital mortality at 30-days was 1.3%. The overall morbidity rate was 28% and major morbidity occurred in 6%. Surgical clearance was achieved in all cases without local recurrence. For BCLC 0-A, B, and C the 3-year overall survival was respectively: 81%; 67%; 74% (P = 0.235). Similarly, the 3-year disease-free survival was respectively: 30%; 35%; 15% (P = 0.853). The 3-year hepatic disease-free survival was respectively: 39%; 44%; 17% (P = 0.791). Conclusions: This study showed that hepatic resection might offer survival benefits for patients with HCC in BCLC class B and C when resection is feasible and safe under strict IOUS guidance. These results should induce to reconsider the BCLC treatment recommendations.
Parallel Session 4: ALCOHOLIC LIVER DISEASE AND NAFLD
31 VALIDATION OF A DIAGNOSTIC BIOMARKER PANEL FOR NON-ALCOHOLIC STEATOHEPATITIS (NASH) Z.M. Younossi1,2,3 , M. Jarrar2,3 , C. Nugent1,3 , M. Randhawa2,3 , M. Afendy1,3 , M. Stepanova1,3 , A. Afendy1,3 , N. Rafiq1,3 , Z. Goodman4 , V. Chandhoke2,3 , A. Baranova1,2,3 . 1 Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, 2 Center for the Study of Genomics in Liver Diseases, Molecular and Microbiology Department, George Mason University, Fairfax, VA, 3 Translational Research Institute, Inova Health System, Falls Church, VA, 4 Armed Forces Institute of Pathology, Washington DC, VI, USA E-mail: [email protected] Background: Within the spectrum of non-alcoholic fatty liver disease (NAFLD), only patients with biopsy-proven NASH have convincingly been shown to progress. Given that liver biopsy is expensive with an associated small risk, there is a need to develop non-invasive diagnostic biomarkers for NASH. Recent data suggest that apoptosis and adipo-cytokines play an important role in the pathogenesis of NASH. Aim: To validate a non-invasive diagnostic biomarker for NASH. Methods: A total of 101 NAFLD patients with available liver biopsies were included. All liver biopsies were interpreted by a single hepatopathologist. NASH was defined as steatosis, lobular inflammation and ballooning degeneration with or without Mallory hyalines and/or fibrosis. Of patients enrolled, 69 were included in the Biomarker Development Set and 32 were included in the Biomarker Validation Set. Clinical data and serum samples were collected at the time of biopsy. Fasting serum was assayed for adiponectin, resistin, insulin, glucose, TNF-alpha, IL-6, IL-8, Cytokeratin CK-18, and caspase cleaved CK-18. Results: Data analysis revealed that histologic NASH could be reliably predicted by a panel which included four components: 1) Cleaved CK-18, 2) A serum marker of necrosis (obtained by subtracting Cleaved CK18 from intact CK-18), 3) Serum adiponectin, and 4) Serum resistin. This panel had a sensitivity of 95.45% sensitivity, specificity of 70.21%, and AUC of 0.908 (p < 10−4 ) for diagnosing NASH. Blinded validation of this panel using the Biomarker Validation set of NAFLD patients confirmed its ability to accurately separate NASH from Simple Steatosis. Extension of the model to the entire NAFLD cohort suggested an optimal threshold of 0.4320 for the panel with AUC of 0.854 (95% CI 0.770−0.917, p < 2.1×10−7 ).
Thursday, 24 April
29 NEITHER MULTIPLE TUMORS NOR PORTAL HYPERTENSION ARE OPERATIVE CONTRAINDICATIONS FOR HEPATOCELLULAR CARCINOMA T. Ishizawa, K. Hasegawa, T. Aoki, M. Takahashi, Y. Inoue, H. Imamura, Y. Sugawara, N. Kokudo, M. Makuuchi. Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan E-mail: [email protected] Background and Aims: The surgical indications for multiple hepatocellular carcinomas (HCCs) and for HCC with portal hypertension (PHT) remain controversial. Methods: We reviewed 434 patients who had undergone an initial resection for HCC and divided them into multiple (n = 126) and single (n = 308) groups according to the tumor number. We also classified 386 of them into PHT (n = 136) and no PHT (n = 250) groups, according to the definition of PHT (the presence of esophageal varices or platelet count <100,000/mL associated with splenomegaly). The indications for liver resection and operative procedures were determined according to the decision criteria based on the presence or absence of uncontrolled ascites, the serum bilirubin level, and the indocyanine green retention rate at 15 minutes. Results: Among Child-Pugh class A patients, the overall survival rates were satisfactory, even in the multiple group (58% at 5 years) and the PHT group (56%), although they were lower than those in the single (68%, P = 0.035) or the no PHT groups (71%, P = 0.008), respectively. The cumulative recurrence rates for Child-Pugh class A patients were higher in the multiple group (75% at 5 years) and the PHT group (75%) than those in the single (60%, P < 0.001) or the no PHT groups (58%, P = 0.008), respectively. Long-term results in Child-Pugh class B patients with multiple HCCs were unsatisfactory (the 5-year overall survival rate and cumulative recurrence rate were 19% and 100%, respectively). Multivariate analyses revealed that the presence of multiple tumors independently increased a risk of postoperative recurrence (relative risk, 1.64; 95% confidence interval, 1.23−2.18; P = 0.001). A second resection provided a satisfactory overall survival after the diagnosis of recurrence in the multiple (73% at 3 years) or PHT (73%) groups as well as in the single (79%) or no PHT (81%) groups. Conclusions: Resection can provide survival benefits even for patients with multiple tumors in a background of Child-Pugh class A cirrhosis as well as in those with PHT. 30 ROLE OF SURGICAL RESECTION FOR HEPATOCELLULAR CARCINOMA IN THE BARCELONA-CLINIC-LIVER-CANCER CLASSIFICATION: A PROSPECTIVE STUDY M. Donadon, F. Procopio, D. Del Fabbro, F. Botea, A. Palmisano, M. Marconi, M. Montorsi, G. Torzilli. Third Department of Surgery, University of Milan, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy E-mail: [email protected] Background: For patients with multiple and/or with vascular invasive hepatocellular carcinoma (HCC) palliation is the only feasible approach according with the Barcelona-Clinic-Liver-Cancer classification (BCLC). However, some authors reported survival benefit after surgery even in more advanced patients. We prospectively evaluated the short- and longterm outcome of patients resected for HCC based on a selection process, in which the BCLC intermediate and advanced stages were not contraindicated. Methods: Patients wee selected for surgery based on presence-absence of ascites, serum bilirubin level and expected remnant liver volume. Esophageal varices were not a contraindication once eradicated endoscopically. Surgical strategy was based on the relationship between the tumor and the intrahepatic vascular structures at intraoperative ultrasonography
(IOUS). Mortality, morbidity, rate of cut-edge local recurrences, and longterm outcome were evaluated. A P value less than 0.05 was considered statistically significant. Results: One-hundred-fifty-two patients underwent surgery and 143 (94%) were resected: of them, 81 were BCLC stage 0-A, 34 B, and 28 C. The BCLC C stage was, in all patients, due to macroscopic vascular invasion. Hospital mortality at 30-days was 1.3%. The overall morbidity rate was 28% and major morbidity occurred in 6%. Surgical clearance was achieved in all cases without local recurrence. For BCLC 0-A, B, and C the 3-year overall survival was respectively: 81%; 67%; 74% (P = 0.235). Similarly, the 3-year disease-free survival was respectively: 30%; 35%; 15% (P = 0.853). The 3-year hepatic disease-free survival was respectively: 39%; 44%; 17% (P = 0.791). Conclusions: This study showed that hepatic resection might offer survival benefits for patients with HCC in BCLC class B and C when resection is feasible and safe under strict IOUS guidance. These results should induce to reconsider the BCLC treatment recommendations.
Parallel Session 4: ALCOHOLIC LIVER DISEASE AND NAFLD
31 VALIDATION OF A DIAGNOSTIC BIOMARKER PANEL FOR NON-ALCOHOLIC STEATOHEPATITIS (NASH) Z.M. Younossi1,2,3 , M. Jarrar2,3 , C. Nugent1,3 , M. Randhawa2,3 , M. Afendy1,3 , M. Stepanova1,3 , A. Afendy1,3 , N. Rafiq1,3 , Z. Goodman4 , V. Chandhoke2,3 , A. Baranova1,2,3 . 1 Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, 2 Center for the Study of Genomics in Liver Diseases, Molecular and Microbiology Department, George Mason University, Fairfax, VA, 3 Translational Research Institute, Inova Health System, Falls Church, VA, 4 Armed Forces Institute of Pathology, Washington DC, VI, USA E-mail: [email protected] Background: Within the spectrum of non-alcoholic fatty liver disease (NAFLD), only patients with biopsy-proven NASH have convincingly been shown to progress. Given that liver biopsy is expensive with an associated small risk, there is a need to develop non-invasive diagnostic biomarkers for NASH. Recent data suggest that apoptosis and adipo-cytokines play an important role in the pathogenesis of NASH. Aim: To validate a non-invasive diagnostic biomarker for NASH. Methods: A total of 101 NAFLD patients with available liver biopsies were included. All liver biopsies were interpreted by a single hepatopathologist. NASH was defined as steatosis, lobular inflammation and ballooning degeneration with or without Mallory hyalines and/or fibrosis. Of patients enrolled, 69 were included in the Biomarker Development Set and 32 were included in the Biomarker Validation Set. Clinical data and serum samples were collected at the time of biopsy. Fasting serum was assayed for adiponectin, resistin, insulin, glucose, TNF-alpha, IL-6, IL-8, Cytokeratin CK-18, and caspase cleaved CK-18. Results: Data analysis revealed that histologic NASH could be reliably predicted by a panel which included four components: 1) Cleaved CK-18, 2) A serum marker of necrosis (obtained by subtracting Cleaved CK18 from intact CK-18), 3) Serum adiponectin, and 4) Serum resistin. This panel had a sensitivity of 95.45% sensitivity, specificity of 70.21%, and AUC of 0.908 (p < 10−4 ) for diagnosing NASH. Blinded validation of this panel using the Biomarker Validation set of NAFLD patients confirmed its ability to accurately separate NASH from Simple Steatosis. Extension of the model to the entire NAFLD cohort suggested an optimal threshold of 0.4320 for the panel with AUC of 0.854 (95% CI 0.770−0.917, p < 2.1×10−7 ).