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W1775 Significance of Perihepatic Lymphadenopathy in Patients with Cirrhosis Undergoing Liver Transplantation
HCV-infected patients with HCC still do not receive any specific potentially curative or palliative therapies. The reasons for this possible underutilization need to be examined.
W1776
W1774 Cost Effectiveness of Radiofrequency Ablation Versus Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma Less Than 4.5 CM in Diameter Robert Rahimi, Clark Hair, George Stukenborg, Abdullah M. Al-Osaimi, Curtis K. Argo, Patrick G. Northup, Stephen H. Caldwell Background: While 5 year survival and tumor progression after radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) have been studied, data on cost-effectiveness (CE) comparing these 2 procedures are lacking. Using Markov models, we assessed whether RFA or TACE was more costeffective. Methods: Clinical and financial data were obtained for RFA or TACE patients from June 2006 - June 2008. Patient's age, gender, tumor size, treatment course, and direct costs were recorded. Costs of complications were excluded when entering direct procedure costs into the model. Probabilities of tumor progression after RFA or TACE were obtained from published studies. Data was analyzed using TreeAge Pro 2008 Suite 1.2 (TreeAge Software Inc, Williamstown, MA). A Markov model was developed to compare costs and survival outcomes over 5 years, and sensitivity analyses assessed whether model results were stable within plausible ranges of the estimated components. Results: 95 patients were evaluated, 16 received RFA (age = 62.5 ± 11.4 yrs; 10M), and 79 received TACE (age = 64.4 ± 10.6 yrs; 58M). Average tumor size for RFA was 2.23 x 1.84 cm ± 0.96 x 0.83 cm, while for TACE was 3.02 x 2.43 cm ± 1.38 x 1.31 cm. The baseline estimate of the probability of tumor progression after RFA was 0.056 (range = 0.036-0.06) and with TACE was 0.43 (range = 0.19-0.68). Average cost of RFA is $3133 (range=$1760 to $8063) while TACE is $6828 (range=$6687 to $7132). The incremental cost-effectiveness ratio average is $2908 (range= $2086 to $3730). Over 5 years, RFA direct costs were $9,373 with 4.54 life years obtained, while direct costs for TACE were $15,791 with 1.87 life years obtained. Results from the model were not sensitive to any estimated component. Conclusions: Identifying direct costs and overall effects of non-surgical therapies are important factors to consider in managing HCC. Our analysis indicates that RFA is the most cost-effective strategy across all ranges of direct costs when compared to TACE. While RFA had a wider range of direct costs, results from the Markov model demonstrate that RFA is more cost-effective than TACE for any plausible range of estimates for cost and tumor progression. Future randomized controlled trials are needed to compare CE of all non-surgical therapies for HCC.
Background: Hepatocellular carcinoma (HCC) has become the fifth most common cancer worldwide and the third most fatal. Curative resection is feasible in less than 10% of patients due to their underlying liver disease. Thus, there is clearly a need for new clinical interventions. Methods: Our group established and utilized an In Vitro HCC and In Vivo rat HCC model with reproducible hepatic tumors to examine the utility of laser-induced local heating of cellular structures (through photothermal (PT) mechanisms), mediated by lightabsorbing nanoparticles. 106 rat H4IIE HCC cells were inoculated into hepatic lobes of male ACI rats to generate hepatic tumors. Tumor derived HCC cells from In Vivo resected HCC samples were isolated, cultured and utilized to examine the effect of nanoparticles (NP) acting as localized sources of laser-induced heat leading to nano-thermolysis and consequent cellular damage and death. Uncoated gold/gold sulfide nanoparticles (GNP), with a peak resonance of 830 nm were utilized. Samples were diluted to an optical density (OD) of 1.0 and 2.0 corresponding to a concentration of approximately 1x1011 (GNP1) and 2x1011 (GNP2) particles respectively. Cells were grown, rinsed and incubated with GNP in media for 6 hours prior to laser irradiation. Laser irradiation was accomplished using an Integrated Fiber Array Packet, FAP-I System, with a wavelength of 818 nm (Coherent, Santa Clara, CA) using laser outputs of 2-6 Watts. Cell survival and death was assessed via MTT and quantitative DNA fragmentation analysis. Results: Histopathological analysis of the tumors at 21 days demonstrated that they had retained diminished trabecular structure and neo-vasculature along with increased cell density. Hepatic tissue removed from the nontumor-burdened lobes was confirmed as histologically normal and without micrometastasis. Examination of the effect of GNP and laser on the tumor derived cells showed that GNP or laser irradiation had no significant impact on the survival of the hepatic tumor cells. However, the combined effect of GNP plus laser irradiation led to a dramatic loss of cell survival involving necrotic and apoptotic forms of cell death. Notably, the combination of GNP and laser irradiation generated a high degree of synergy in drastically reducing tumor cell survival with the induction of apoptotic death involving caspase-dependent DNA fragmentation. Conclusions: Overall these data demonstrate a novel In Vitro and In Vivo model for HCC therapeutic testing. GNP in combination with laser irradiation In Vitro is an efficacious therapeutic approach against HCC and is currently being evaluated in the In Vivo model for HCC.
W1775
W1777
Significance of Perihepatic Lymphadenopathy in Patients with Cirrhosis Undergoing Liver Transplantation Muhammad A. Asim, Saleem Farooqui, Muhammad Bilal, Meer A. Ali, Satheesh Nair
the Impact of Ethnicity On the Presentation and Prognosis of Hepatocellular Carcinoma Raul Cubillas, Richard Guerrero, Geri Brown
Perihepatic lymphadenopathy, found incidentally during a liver transplant evaluation raises the concern for lymphoma or metastatic involvement from hepatocellular carcinoma Aim: To find the prevalence of enlarged perihepatic lymph nodes in cirrhosis and correlate with etiology and stage of hepatocellular carcinoma. Method: The following data was extracted from 154 consecutive patients(100 males, 54 females, median age 53 yrs, 120 Caucasians and 28 African Americans and 6 Hispanics) who underwent liver transplantation: the etiology of cirrhosis, liver function tests,AFP level,and MELD score. The diagnosis and stage of HCC was determined after reviewing the explant pathology by a single pathologist. Explanted livers in our institution are routinely examined in thin sections to look for HCC. Patients also undergo either chemoembolization or radiofrequency ablation while waiting for transplantation. Lymph node biopsies were also reviewed whenever available. All the pre transplant imaging studies were reexamined by a single radiologist (SF) to determine the lymph node size and distribution. Fisher Exact test and Mann-Whitney U test were used for comparing categorical and continuous variables respectively. A p value of less than 0.05 was considered significant. Results: The etiology of cirrhosis was chronic viral hepatitis (n=87), autoimmune (PBC, PSC, AIH n=26), Chemical (n=26), Metabolic (n=8), miscellaneous (n=7). Enlarged lymph nodes were found in 48% viral, 38% autoimmune, 40% chemical , 25% metabolic and 42% miscellanoeous group.Univariate analysis of different variables with presence and absence of enlarged lymph nodes is shown in table 2. Prevalence of ELN in cirrhosis was found to be 39.6% (68/154).No statistically significant variation in frequency, location or size of ELN was seen with different etiologies of cirrhosis. Forty one patients (26%)had HCC as per the explant pathology. Nineteen patients were T1,19 were T2 and 2 were T3 (By AJCC 6 criteria). In one patient, who had an RFA prior to transplant, explant pathology did not show HCC (but had classical radiological features prior to transplant). 22 patients (53%) with HCC had lymphadenopathy (p value =NS)Presence of lymphadenopathy did not correlate with stage/vascular invasion of HCC. Conclusion: Enlarged perihepatic lymph nodes are common in patients with cirrhosis and do not correlate with etiology or presence of hepatocellular carcinoma. Table 1.Univariate analysis of prevalence of ELN.
Background: Previous studies have found that the frequency of certain clinical features of hepatocellular carcinoma (HCC) can vary among different ethnic groups in the United States. However, those studies did not focus on veteran patients, who have a high prevalence of chronic hepatitis C, a known risk factor for HCC. Our aim was to explore the influence of ethnicity on HCC presentation, treatment and survival in veteran patients. Methods: We conducted a retrospective, cohort study of patients with a confirmed diagnosis of HCC at the Dallas VA Medical Center between January 2002 and July 2008. Patient demographics (age, risk factor), tumor-related features on initial presentation (diagnosis by screening, Barcelona Clinic Liver Cancer [BCLC] staging, portal vein thrombosis [PVT], alpha-fetoprotein [AFP]), treatments administered and overall survival were compared between white, African-American (AA) and Hispanic patients. Results: We identified 179 patients with HCC; 109 (60.9%) white, 51 (28.5%) AA and 19 (10.6%) Hispanic. The prevalence of viral induced HCC was significantly higher in AA patients (96%) than in white (82%) or Hispanic (63%) patients (p=0.001). PVT was significantly more common in AA patients (37%) than in white (20%) or Hispanic (11%) patients (p=0.03), and later stages (BCLC C and D) were found more frequently at presentation for AA patients (59%) than for white (36%) or Hispanic (36%) patients (p=0.02). Multivariable logistic regression confirmed that AA patients presented at later stages compared to whites (odds ratio [OR], 3.08; 95% confidence interval [CI], 1.123-8.485). Sixty-six of the total 179 patients (37%) received treatment for HCC. Multivariable logistic regression revealed that patients with earlier HCC stages (BCLC 0, A and B) were more likely to receive treatment than those with later stages (OR, 9.5; 95% CI, 2.7-32.9), irrespective of ethnicity. The median overall survival was 8 months, and there was no significant difference among the ethnic groups (log-rank test, p=0.26). A Cox proportional-hazard model showed that later stages at diagnosis increased mortality risk (hazard ratio [HR], 3.74; 95% CI, 1.97-7.1) and that treatment was the strongest predictor of survival (HR, 0.07; 95% CI, 0.03-0.14); the model showed no significant influence of ethnicity on mortality. Conclusions: Viral induced HCC, PVT and later stages on initial presentation are more frequent in AA than whites or Hispanic veterans. Nevertheless, there is no significant difference in survival among the ethnic groups. The administration of HCC treatment is associated with improved survival, irrespective of ethnicity. W1778 Relationships Among Type 2 Diabetes Mellitus, Antidiabetic Therapy and Hepatocellular Carcinoma Antonio Perciaccante, Massimiliano Balbi, Pietro Casarin, Giorgio Zanette, Valter Donadon Background and aims: Type 2 diabetes mellitus (DM2) is associated with increased risk and mortality for cancer, particularly hepatocellular carcinoma (HCC). The aims of this study are to evaluate the prevalence of DM2 in various etiologies of HCC patients, describe the timing between the onset of diabetes and the development of HCC and investigate the effects of antidiabetic therapy on HCC risk. Research Design and Methods: we recruited 465 HCC patients compared with 618 cirrhotics and 490 control subjects. We evaluated the prevalence
ELN Enlarged lymph nodes MW Mann-Whittney U test FE Fisher Exact test
A-859
AASLD Abstracts
AASLD Abstracts
Development and Evaluation of Gold Nanoparticle Based Laser Nano Thermolysis As a Potential New Active Intervention: A Novel Therapeutic Approach to Hepatocellular Cancer Joseph Buell, Swati Joshi-Barve, Andre Gobin, Leila Gobejishvili, Jingwen Zhang, Yan Li, Craig J. McClain, Shirish Barve
W1776
W1774 Cost Effectiveness of Radiofrequency Ablation Versus Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma Less Than 4.5 CM in Diameter Robert Rahimi, Clark Hair, George Stukenborg, Abdullah M. Al-Osaimi, Curtis K. Argo, Patrick G. Northup, Stephen H. Caldwell Background: While 5 year survival and tumor progression after radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) have been studied, data on cost-effectiveness (CE) comparing these 2 procedures are lacking. Using Markov models, we assessed whether RFA or TACE was more costeffective. Methods: Clinical and financial data were obtained for RFA or TACE patients from June 2006 - June 2008. Patient's age, gender, tumor size, treatment course, and direct costs were recorded. Costs of complications were excluded when entering direct procedure costs into the model. Probabilities of tumor progression after RFA or TACE were obtained from published studies. Data was analyzed using TreeAge Pro 2008 Suite 1.2 (TreeAge Software Inc, Williamstown, MA). A Markov model was developed to compare costs and survival outcomes over 5 years, and sensitivity analyses assessed whether model results were stable within plausible ranges of the estimated components. Results: 95 patients were evaluated, 16 received RFA (age = 62.5 ± 11.4 yrs; 10M), and 79 received TACE (age = 64.4 ± 10.6 yrs; 58M). Average tumor size for RFA was 2.23 x 1.84 cm ± 0.96 x 0.83 cm, while for TACE was 3.02 x 2.43 cm ± 1.38 x 1.31 cm. The baseline estimate of the probability of tumor progression after RFA was 0.056 (range = 0.036-0.06) and with TACE was 0.43 (range = 0.19-0.68). Average cost of RFA is $3133 (range=$1760 to $8063) while TACE is $6828 (range=$6687 to $7132). The incremental cost-effectiveness ratio average is $2908 (range= $2086 to $3730). Over 5 years, RFA direct costs were $9,373 with 4.54 life years obtained, while direct costs for TACE were $15,791 with 1.87 life years obtained. Results from the model were not sensitive to any estimated component. Conclusions: Identifying direct costs and overall effects of non-surgical therapies are important factors to consider in managing HCC. Our analysis indicates that RFA is the most cost-effective strategy across all ranges of direct costs when compared to TACE. While RFA had a wider range of direct costs, results from the Markov model demonstrate that RFA is more cost-effective than TACE for any plausible range of estimates for cost and tumor progression. Future randomized controlled trials are needed to compare CE of all non-surgical therapies for HCC.
Background: Hepatocellular carcinoma (HCC) has become the fifth most common cancer worldwide and the third most fatal. Curative resection is feasible in less than 10% of patients due to their underlying liver disease. Thus, there is clearly a need for new clinical interventions. Methods: Our group established and utilized an In Vitro HCC and In Vivo rat HCC model with reproducible hepatic tumors to examine the utility of laser-induced local heating of cellular structures (through photothermal (PT) mechanisms), mediated by lightabsorbing nanoparticles. 106 rat H4IIE HCC cells were inoculated into hepatic lobes of male ACI rats to generate hepatic tumors. Tumor derived HCC cells from In Vivo resected HCC samples were isolated, cultured and utilized to examine the effect of nanoparticles (NP) acting as localized sources of laser-induced heat leading to nano-thermolysis and consequent cellular damage and death. Uncoated gold/gold sulfide nanoparticles (GNP), with a peak resonance of 830 nm were utilized. Samples were diluted to an optical density (OD) of 1.0 and 2.0 corresponding to a concentration of approximately 1x1011 (GNP1) and 2x1011 (GNP2) particles respectively. Cells were grown, rinsed and incubated with GNP in media for 6 hours prior to laser irradiation. Laser irradiation was accomplished using an Integrated Fiber Array Packet, FAP-I System, with a wavelength of 818 nm (Coherent, Santa Clara, CA) using laser outputs of 2-6 Watts. Cell survival and death was assessed via MTT and quantitative DNA fragmentation analysis. Results: Histopathological analysis of the tumors at 21 days demonstrated that they had retained diminished trabecular structure and neo-vasculature along with increased cell density. Hepatic tissue removed from the nontumor-burdened lobes was confirmed as histologically normal and without micrometastasis. Examination of the effect of GNP and laser on the tumor derived cells showed that GNP or laser irradiation had no significant impact on the survival of the hepatic tumor cells. However, the combined effect of GNP plus laser irradiation led to a dramatic loss of cell survival involving necrotic and apoptotic forms of cell death. Notably, the combination of GNP and laser irradiation generated a high degree of synergy in drastically reducing tumor cell survival with the induction of apoptotic death involving caspase-dependent DNA fragmentation. Conclusions: Overall these data demonstrate a novel In Vitro and In Vivo model for HCC therapeutic testing. GNP in combination with laser irradiation In Vitro is an efficacious therapeutic approach against HCC and is currently being evaluated in the In Vivo model for HCC.
W1775
W1777
Significance of Perihepatic Lymphadenopathy in Patients with Cirrhosis Undergoing Liver Transplantation Muhammad A. Asim, Saleem Farooqui, Muhammad Bilal, Meer A. Ali, Satheesh Nair
the Impact of Ethnicity On the Presentation and Prognosis of Hepatocellular Carcinoma Raul Cubillas, Richard Guerrero, Geri Brown
Perihepatic lymphadenopathy, found incidentally during a liver transplant evaluation raises the concern for lymphoma or metastatic involvement from hepatocellular carcinoma Aim: To find the prevalence of enlarged perihepatic lymph nodes in cirrhosis and correlate with etiology and stage of hepatocellular carcinoma. Method: The following data was extracted from 154 consecutive patients(100 males, 54 females, median age 53 yrs, 120 Caucasians and 28 African Americans and 6 Hispanics) who underwent liver transplantation: the etiology of cirrhosis, liver function tests,AFP level,and MELD score. The diagnosis and stage of HCC was determined after reviewing the explant pathology by a single pathologist. Explanted livers in our institution are routinely examined in thin sections to look for HCC. Patients also undergo either chemoembolization or radiofrequency ablation while waiting for transplantation. Lymph node biopsies were also reviewed whenever available. All the pre transplant imaging studies were reexamined by a single radiologist (SF) to determine the lymph node size and distribution. Fisher Exact test and Mann-Whitney U test were used for comparing categorical and continuous variables respectively. A p value of less than 0.05 was considered significant. Results: The etiology of cirrhosis was chronic viral hepatitis (n=87), autoimmune (PBC, PSC, AIH n=26), Chemical (n=26), Metabolic (n=8), miscellaneous (n=7). Enlarged lymph nodes were found in 48% viral, 38% autoimmune, 40% chemical , 25% metabolic and 42% miscellanoeous group.Univariate analysis of different variables with presence and absence of enlarged lymph nodes is shown in table 2. Prevalence of ELN in cirrhosis was found to be 39.6% (68/154).No statistically significant variation in frequency, location or size of ELN was seen with different etiologies of cirrhosis. Forty one patients (26%)had HCC as per the explant pathology. Nineteen patients were T1,19 were T2 and 2 were T3 (By AJCC 6 criteria). In one patient, who had an RFA prior to transplant, explant pathology did not show HCC (but had classical radiological features prior to transplant). 22 patients (53%) with HCC had lymphadenopathy (p value =NS)Presence of lymphadenopathy did not correlate with stage/vascular invasion of HCC. Conclusion: Enlarged perihepatic lymph nodes are common in patients with cirrhosis and do not correlate with etiology or presence of hepatocellular carcinoma. Table 1.Univariate analysis of prevalence of ELN.
Background: Previous studies have found that the frequency of certain clinical features of hepatocellular carcinoma (HCC) can vary among different ethnic groups in the United States. However, those studies did not focus on veteran patients, who have a high prevalence of chronic hepatitis C, a known risk factor for HCC. Our aim was to explore the influence of ethnicity on HCC presentation, treatment and survival in veteran patients. Methods: We conducted a retrospective, cohort study of patients with a confirmed diagnosis of HCC at the Dallas VA Medical Center between January 2002 and July 2008. Patient demographics (age, risk factor), tumor-related features on initial presentation (diagnosis by screening, Barcelona Clinic Liver Cancer [BCLC] staging, portal vein thrombosis [PVT], alpha-fetoprotein [AFP]), treatments administered and overall survival were compared between white, African-American (AA) and Hispanic patients. Results: We identified 179 patients with HCC; 109 (60.9%) white, 51 (28.5%) AA and 19 (10.6%) Hispanic. The prevalence of viral induced HCC was significantly higher in AA patients (96%) than in white (82%) or Hispanic (63%) patients (p=0.001). PVT was significantly more common in AA patients (37%) than in white (20%) or Hispanic (11%) patients (p=0.03), and later stages (BCLC C and D) were found more frequently at presentation for AA patients (59%) than for white (36%) or Hispanic (36%) patients (p=0.02). Multivariable logistic regression confirmed that AA patients presented at later stages compared to whites (odds ratio [OR], 3.08; 95% confidence interval [CI], 1.123-8.485). Sixty-six of the total 179 patients (37%) received treatment for HCC. Multivariable logistic regression revealed that patients with earlier HCC stages (BCLC 0, A and B) were more likely to receive treatment than those with later stages (OR, 9.5; 95% CI, 2.7-32.9), irrespective of ethnicity. The median overall survival was 8 months, and there was no significant difference among the ethnic groups (log-rank test, p=0.26). A Cox proportional-hazard model showed that later stages at diagnosis increased mortality risk (hazard ratio [HR], 3.74; 95% CI, 1.97-7.1) and that treatment was the strongest predictor of survival (HR, 0.07; 95% CI, 0.03-0.14); the model showed no significant influence of ethnicity on mortality. Conclusions: Viral induced HCC, PVT and later stages on initial presentation are more frequent in AA than whites or Hispanic veterans. Nevertheless, there is no significant difference in survival among the ethnic groups. The administration of HCC treatment is associated with improved survival, irrespective of ethnicity. W1778 Relationships Among Type 2 Diabetes Mellitus, Antidiabetic Therapy and Hepatocellular Carcinoma Antonio Perciaccante, Massimiliano Balbi, Pietro Casarin, Giorgio Zanette, Valter Donadon Background and aims: Type 2 diabetes mellitus (DM2) is associated with increased risk and mortality for cancer, particularly hepatocellular carcinoma (HCC). The aims of this study are to evaluate the prevalence of DM2 in various etiologies of HCC patients, describe the timing between the onset of diabetes and the development of HCC and investigate the effects of antidiabetic therapy on HCC risk. Research Design and Methods: we recruited 465 HCC patients compared with 618 cirrhotics and 490 control subjects. We evaluated the prevalence
ELN Enlarged lymph nodes MW Mann-Whittney U test FE Fisher Exact test
A-859
AASLD Abstracts
AASLD Abstracts
Development and Evaluation of Gold Nanoparticle Based Laser Nano Thermolysis As a Potential New Active Intervention: A Novel Therapeutic Approach to Hepatocellular Cancer Joseph Buell, Swati Joshi-Barve, Andre Gobin, Leila Gobejishvili, Jingwen Zhang, Yan Li, Craig J. McClain, Shirish Barve