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Figure 1: Association of hepatocellular carcinoma with HBV and HCV by ethnicity Sa1848 Radiofrequency Ablation Using a Balloon Catheter for Hepatocellular Carcinoma Adjacent to the Gastrointestinal Tract: Experimental and Clinical Study Hidetaka Takenaka, Katsuyoshi Tamaki, Tatsuya Taniguchi, Tetsu Tomonari, Rie Harada, Katsutaka Sannomiya, Momoko Sato, Toshiya Okahisa, Seisuke Okamura, Tetsuji Takayama Purpose: Radiofrequency ablation (RFA) is a safe and effective technique for hepatocellular carcinoma and it has minimal morbidity and mortality. One of the most important major complications of RFA is perforation of the gastrointestinal tract, which occurs when the tumor is adjacent to the digestive tract. In particular, the risk is much higher in patients with lesions located within 1 cm from the liver surface in proximity to the digestive tract. In such cases, an artificial ascites technique has been employed. However, the separation of adjacent digestive organ from the liver is insufficient in this method. Therefore, in this study, to overcome this problem, we devised a novel RFA technique using a double-balloon catheter. In the first step, an animal experiment was performed to evaluate the safety and feasibility of the balloon RFA method. In the second step, the human pilot trial was carried out to evaluate the safety, feasibility and effectiveness of this method. Materials and Methods: We produced an 8 Fr silicone catheter equipped with 2 balloons of 2.5 cm diameter. In experiments using pigs, we first inserted this balloon catheter percutaneously into the peritoneal space between the liver and gastrointestinal tracts, filled it with cooled water, and performed RFA for in normal liver 1 cm from the liver surface. Then, heat damage to the excised liver and gastrointestinal tract was evaluated macroscopically and microscopically. In a human pilot study, balloon catheter RFA was performed in 4 patients with HCC (1.5 ± 0.7 cm) abutting the gastrointestinal tract. Results: In pigs, we performed each 6 RFA sessions with or without balloon catheter. It was technically easy to place the balloon catheter between liver and gastrointestinal tracts to separate them. Heat damage reached the liver surface in all lesions. In the group with balloon catheter, no heat damage of the gastrointestinal tracts was observed (0%, 0/6). In contrast, in the group without balloon catheter, heat damage was observed in 5/6 (83.3%): stomach (2/6), small intestine (2/6), and omentum (1/6). The coolant temperature in the balloon was significantly increased after RFA, suggesting that the heat generated by RFA was absorbed by the coolant. In the human pilot study, balloon catheter RFA was easily performed in all patients without associated complications. CT confirmed complete ablation with an appreciable safety margin in all patients, without recurrence for 20.3 ± 4.5 months. Conclusions: RFA with our balloon catheter is safe and effective for the treatment of HCC abutting the gastrointestinal tract, suggesting an expanded indication of these lesions for RFA. Sa1849 Serum Ferritin Level and Risk of Liver Cancer Development in Patients With Chronic Liver Diseases Koji Uchino, Ryosuke Tateishi, Hayato Nakagawa, Toru Arano, Kenichiro Enooku, Eriko Goto, Ryota Masuzaki, Yuji Kondo, Yoshinari Asaoka, Tadashi Goto, Shuichiro Shiina, Hitoshi Ikeda, Masao Omata, Haruhiko Yoshida, Kazuhiko Koike Backgrounds and Aims: Elevated serum ferritin level indicates increased liver iron concentra- tion that leads to exacerbation of hepatic necroinflammation in chronic liver diseases. The aim of this study was to determine whether serum ferritin concentration is a risk factor for liver cancer development in chronic viral and non-viral liver diseases. Methods: We measured serum ferritin levels in 520 patients (mean age=61.8 ±11.5 yrs, M/F=234/286) who visited the authors' liver clinic between January 2004 and December 2005. Patients with hepatocellular carcinoma (HCC), iron-deficient anemia or decompensated disease at visit were excluded. They were divided into 5 groups according to serum ferritin levels: G1 (100 ng/mL, N= 270), G2 (101-200 ng/mL, N=132), G3 (201-300 ng/mL, N=41), G4 (301-400 ng/mL, N= 36) and G5 (>400 ng/mL, N=41). Patients were followed by periodical ultrasonography with tumor markers for HCC development. We assessed the impact of serum ferritin level on the hepatocarcinogenesis adjusted by multivariate Cox proportional hazard regression with other risk factors found significant in univariate analysis. Results: During mean follow up period of 3.4 years, HCC developed in 55 patients. A V-shape relationship between serum ferritin levels and risk of HCC development was observed by univariate analysis using G2 as a reference (hazard ratio [HR] for G1, G3, G4 and G5 were 1.63, 2.19, 2.86 and 3.69, respectively). Multivariate analysis with stepwise variable selection revealed that serum ferritin level > 400 ng/mL was a significant risk factor for HCC development (HR=2.492, p=0.02) along with sex, age, serum albumin level and liver stiffness measured by Fibroscan. Conclusions: Low ferritin levels might be a surrogate marker for more advanced disease. Excessive serum ferritin was a risk factor for HCC development in patients with chronic liver diseases. S-925 AASLD Abstracts Sa1850 Serum Alfa-Feto Protein Level Does Not Predict Micro-Vascular Invasion in Patients Undergoing Orthotopic Liver Transplantation for Hepatocellular Carcinoma Frank Czul, Andres Yarur, Cynthia Levy, Steven Rueda, Paul Martin Background Multiple systems to predict the prognosis of hepatocellular carcinoma (HCC) have been formulated. Among them vascular invasion is a major determinant of outcome after orthotopic liver transplantation (OLT). Different preoperative means of assessing the probability of micro-vascular invasion (MVI) have been studied in the past. Serum Alfa- fetoprotein (AFP) is a tumor marker, widely used to determine prognosis and recurrence of disease. We sought to identify if serum levels of AFP before the OLT were correlated to the degree of MVI found in the explanted livers. Methods A cohort of 179 patients who underwent OLT for HCC between January of 2004 and December of 2008 at Jackson Memorial Hospital (Miami, FL) were identified, 28 were excluded because AFP was not available. Pathologic evidence of MVI was denoted on 49 (32%) of the studied population. AFP level was recorded before OLT on each patient. Other data such as ethnicity, tumor location, size, level of differentiation and relation to hepatitis B and C was also abstracted. The primary outcome was correlation of AFP levels and MVI defined as invasion of the peripheral portal or hepatic veins in the resected liver. The associations between the continu- ous and the categorical clinico-pathological variables and MVI were analyzed using ANOVA and chi-square test respectively. Logistic regression was used to identify association between MVI and the studied variables. Results Data from 151 patients was abstracted; patients with MVI (n=49,32%) had a mean serum AFP of 137 ng/ml compared to a mean serum AFP of 81,1 ng/ml on patients where MVI was not found (p = 0.54). In the multivariate model, the adjusted OR for developing MVI for AFP level was 1.0 (95%CI 0.98-1.02). Twenty five percent of patients with single tumors and 43% with multiple tumors had MVI (p = 0.02). Only 18% of patients with tumors less than 2 cm had MVI compared to 30% and 78% with tumors greater than 2 to 5 cm and larger than 5 cm, respectively (p = 0.001). Among 120 (79%) patients who had positive hepatitis C antibody, 33% had MVI compared to the counterpart population negative for hepatitis C antibody where 29% had MVI (p = 0.83). Tumor grade was also analyzed: 23% of patients with well-differentiated tumors had MVI, compared to 30% and 75% with moderately or poorly differentiated tumors respectively (p = 0.01). Conclusions In our population, pre-operative serum AFP levels do not correlate with MVI in patients undergoing OLT for hepatocellular carcinoma. The independent pre- dictors of MVI were tumor size greater than 5 cm, tumor grade (poorly differentiated) and multiple tumors. Sa1851 Palliative Care for Hepatocellular Carcinoma Patients Yaa Oppong, Victor J. Navarro, Barbara Reville, Parminder K. Bath Sohal, Susan Parks Management of patients with hepatocellular carcinoma (HCC) is usually focused on medical therapy aimed at prolonging life. The most effective therapy, liver transplantation, is offered by convention only to patients with early stage disease. Few effective therapies are available for patients with advanced HCC which offer a substantive prolongation of life, making palliative care an important intervention in this group. Palliative care focuses on symptom management and end-of-life decision-making during medical care. The National Compre- hensive Cancer Network (NCCN) clinical guidelines support the incorporation of palliative care (PC) into the treatment of cancer at time of diagnosis regardless of stage. However, there is little research on PC interventions for patients with hepatocellular carcinoma (HCC). To expand the body of literature on PC in HCC, we retrospectively examined our center's experience of the frequency of PC interventions, defined as referral to our PC service, hospice program, or discussion about end-of-life preferences, code status, and family meetings, among these patients. Our HCC program is multidisciplinary and has been in place since 2003, caring for approximately 100 patients at any one time. We identified 474 HCC patients treated between 2004 and September 2010. Overall, PC interventions, as defined above, occurred in 62 patients (13%); 8.4% had referral to our inpatient palliative care team and 4.4% to hospice. 3.8% of patients had documented code status, of these, 78% were DNI/ DNR. Family meetings were documented in less than 1% of all patients.186 patients were identified with early disease (stage I), these are patients who at time of diagnosis where eligible for transplant, only 17 (9%) received transplants and none had any end-of-life intervention. PC interventions for patients with advanced HCC were infrequent. Specifically, of 141 patients identified as having advanced HCC, defined as either stage III or IV disease, or involvement of the portal vessels; only 15 (10.6%) had any PC intervention. Our single center experience indicates that any PC intervention is an infrequent occurrence, even in advanced HCC. Given the growing incidence of HCC, and the limited survival despite therapy, particularly for advanced disease, our findings indicate the need for fuller integration of palliative care in this population. Sa1852 The Advantage in Long-Term Survival of Radiofrequency Ablation for Hepatocellular Carcinoma Patients: Historical Comparison With Ethanol Injection Satoshi Oeda, Toshihiko Mizuta, Hiroshi Isoda, Takuya Kuwashiro, Shinji Iwane, Yasunori Kawaguchi, Iwata Ozaki, Kazuma Fujimoto Background and Aim: In 1999, we adopted radiofrequency ablation (RFA) for treatment of small hepatocellular carcinoma (HCC). Since this time, the main local therapy for HCC has shifted from percutaneous ethanol injection (PEI) to RFA. However, little is known on whether there is a difference in the long-term efficacy between the two methods. Therefore, we historically compared the long-term survival rates of HCC patients treated with RFA with those treated with PEI. Patients and Methods: Among 213 patients with HCC who were initially treated with PEI or RFA at Saga Medical School Hospital between 1990 and 2004, we examined 190 patients who could be followed up for more than 3 years after treatment. They consisted of 98 patients treated with PEI (PEI group) from 1990 to 1999 AASLD Abstracts

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Figure 1: Association of hepatocellular carcinoma with HBV and HCV by ethnicity

Sa1848

Radiofrequency Ablation Using a Balloon Catheter for HepatocellularCarcinoma Adjacent to the Gastrointestinal Tract: Experimental and ClinicalStudyHidetaka Takenaka, Katsuyoshi Tamaki, Tatsuya Taniguchi, Tetsu Tomonari, Rie Harada,Katsutaka Sannomiya, Momoko Sato, Toshiya Okahisa, Seisuke Okamura, TetsujiTakayama

Purpose: Radiofrequency ablation (RFA) is a safe and effective technique for hepatocellularcarcinoma and it has minimal morbidity and mortality. One of the most important majorcomplications of RFA is perforation of the gastrointestinal tract, which occurs when thetumor is adjacent to the digestive tract. In particular, the risk is much higher in patientswith lesions located within 1 cm from the liver surface in proximity to the digestive tract.In such cases, an artificial ascites technique has been employed. However, the separationof adjacent digestive organ from the liver is insufficient in this method. Therefore, in thisstudy, to overcome this problem, we devised a novel RFA technique using a double-ballooncatheter. In the first step, an animal experiment was performed to evaluate the safety andfeasibility of the balloon RFA method. In the second step, the human pilot trial was carriedout to evaluate the safety, feasibility and effectiveness of this method. Materials and Methods:We produced an 8 Fr silicone catheter equipped with 2 balloons of 2.5 cm diameter. Inexperiments using pigs, we first inserted this balloon catheter percutaneously into theperitoneal space between the liver and gastrointestinal tracts, filled it with cooled water,and performed RFA for in normal liver 1 cm from the liver surface. Then, heat damage tothe excised liver and gastrointestinal tract was evaluated macroscopically andmicroscopically.In a human pilot study, balloon catheter RFA was performed in 4 patients with HCC (1.5± 0.7 cm) abutting the gastrointestinal tract. Results: In pigs, we performed each 6 RFAsessions with or without balloon catheter. It was technically easy to place the balloon catheterbetween liver and gastrointestinal tracts to separate them. Heat damage reached the liversurface in all lesions. In the groupwith balloon catheter, no heat damage of the gastrointestinaltracts was observed (0%, 0/6). In contrast, in the group without balloon catheter, heatdamage was observed in 5/6 (83.3%): stomach (2/6), small intestine (2/6), and omentum(1/6). The coolant temperature in the balloon was significantly increased after RFA, suggestingthat the heat generated by RFA was absorbed by the coolant. In the human pilot study,balloon catheter RFA was easily performed in all patients without associated complications.CT confirmed complete ablation with an appreciable safety margin in all patients, withoutrecurrence for 20.3 ± 4.5 months. Conclusions: RFA with our balloon catheter is safe andeffective for the treatment of HCC abutting the gastrointestinal tract, suggesting an expandedindication of these lesions for RFA.

Sa1849

Serum Ferritin Level and Risk of Liver Cancer Development in Patients WithChronic Liver DiseasesKoji Uchino, Ryosuke Tateishi, Hayato Nakagawa, Toru Arano, Kenichiro Enooku, ErikoGoto, Ryota Masuzaki, Yuji Kondo, Yoshinari Asaoka, Tadashi Goto, Shuichiro Shiina,Hitoshi Ikeda, Masao Omata, Haruhiko Yoshida, Kazuhiko Koike

Backgrounds and Aims: Elevated serum ferritin level indicates increased liver iron concentra-tion that leads to exacerbation of hepatic necroinflammation in chronic liver diseases. Theaim of this study was to determine whether serum ferritin concentration is a risk factor forliver cancer development in chronic viral and non-viral liver diseases.Methods:Wemeasuredserum ferritin levels in 520 patients (mean age=61.8 ±11.5 yrs, M/F=234/286) who visited theauthors' liver clinic between January 2004 and December 2005. Patients with hepatocellularcarcinoma (HCC), iron-deficient anemia or decompensated disease at visit were excluded.They were divided into 5 groups according to serum ferritin levels: G1 (≤100 ng/mL, N=270), G2 (101-200 ng/mL, N=132), G3 (201-300 ng/mL, N=41), G4 (301-400 ng/mL, N=36) and G5 (>400 ng/mL, N=41). Patients were followed by periodical ultrasonographywith tumor markers for HCC development. We assessed the impact of serum ferritin levelon the hepatocarcinogenesis adjusted by multivariate Cox proportional hazard regressionwith other risk factors found significant in univariate analysis. Results: During mean followup period of 3.4 years, HCC developed in 55 patients. A V-shape relationship betweenserum ferritin levels and risk of HCC development was observed by univariate analysis usingG2 as a reference (hazard ratio [HR] for G1, G3, G4 and G5 were 1.63, 2.19, 2.86 and3.69, respectively). Multivariate analysis with stepwise variable selection revealed that serumferritin level > 400 ng/mL was a significant risk factor for HCC development (HR=2.492,p=0.02) along with sex, age, serum albumin level and liver stiffness measured by Fibroscan.Conclusions: Low ferritin levels might be a surrogate marker for more advanced disease.Excessive serum ferritin was a risk factor for HCC development in patients with chronicliver diseases.

S-925 AASLD Abstracts

Sa1850

Serum Alfa-Feto Protein Level Does Not Predict Micro-Vascular Invasion inPatients Undergoing Orthotopic Liver Transplantation for HepatocellularCarcinomaFrank Czul, Andres Yarur, Cynthia Levy, Steven Rueda, Paul Martin

Background Multiple systems to predict the prognosis of hepatocellular carcinoma (HCC)have been formulated. Among them vascular invasion is a major determinant of outcomeafter orthotopic liver transplantation (OLT). Different preoperative means of assessing theprobability of micro-vascular invasion (MVI) have been studied in the past. Serum Alfa-fetoprotein (AFP) is a tumor marker, widely used to determine prognosis and recurrenceof disease. We sought to identify if serum levels of AFP before the OLT were correlated tothe degree of MVI found in the explanted livers. Methods A cohort of 179 patients whounderwent OLT for HCC between January of 2004 and December of 2008 at JacksonMemorial Hospital (Miami, FL) were identified, 28 were excluded because AFP was notavailable. Pathologic evidence of MVI was denoted on 49 (32%) of the studied population.AFP level was recorded before OLT on each patient. Other data such as ethnicity, tumorlocation, size, level of differentiation and relation to hepatitis B and C was also abstracted.The primary outcome was correlation of AFP levels and MVI defined as invasion of theperipheral portal or hepatic veins in the resected liver. The associations between the continu-ous and the categorical clinico-pathological variables and MVI were analyzed using ANOVAand chi-square test respectively. Logistic regression was used to identify association betweenMVI and the studied variables. Results Data from 151 patients was abstracted; patients withMVI (n=49,32%) had a mean serum AFP of 137 ng/ml compared to a mean serum AFP of81,1 ng/ml on patients where MVI was not found (p = 0.54). In the multivariate model,the adjusted OR for developing MVI for AFP level was 1.0 (95%CI 0.98-1.02). Twenty fivepercent of patients with single tumors and 43% with multiple tumors had MVI (p = 0.02).Only 18% of patients with tumors less than 2 cm had MVI compared to 30% and 78%with tumors greater than 2 to 5 cm and larger than 5 cm, respectively (p = 0.001). Among120 (79%) patients who had positive hepatitis C antibody, 33% had MVI compared to thecounterpart population negative for hepatitis C antibody where 29% had MVI (p = 0.83).Tumor grade was also analyzed: 23% of patients with well-differentiated tumors had MVI,compared to 30% and 75% with moderately or poorly differentiated tumors respectively(p = 0.01). Conclusions In our population, pre-operative serum AFP levels do not correlatewith MVI in patients undergoing OLT for hepatocellular carcinoma. The independent pre-dictors of MVI were tumor size greater than 5 cm, tumor grade (poorly differentiated) andmultiple tumors.

Sa1851

Palliative Care for Hepatocellular Carcinoma PatientsYaa Oppong, Victor J. Navarro, Barbara Reville, Parminder K. Bath Sohal, Susan Parks

Management of patients with hepatocellular carcinoma (HCC) is usually focused on medicaltherapy aimed at prolonging life. The most effective therapy, liver transplantation, is offeredby convention only to patients with early stage disease. Few effective therapies are availablefor patients with advanced HCC which offer a substantive prolongation of life, makingpalliative care an important intervention in this group. Palliative care focuses on symptommanagement and end-of-life decision-making during medical care. The National Compre-hensive Cancer Network (NCCN) clinical guidelines support the incorporation of palliativecare (PC) into the treatment of cancer at time of diagnosis regardless of stage. However,there is little research on PC interventions for patients with hepatocellular carcinoma (HCC).To expand the body of literature on PC in HCC, we retrospectively examined our center'sexperience of the frequency of PC interventions, defined as referral to our PC service, hospiceprogram, or discussion about end-of-life preferences, code status, and family meetings,among these patients. Our HCC program is multidisciplinary and has been in place since2003, caring for approximately 100 patients at any one time. We identified 474 HCC patientstreated between 2004 and September 2010. Overall, PC interventions, as defined above,occurred in 62 patients (13%); 8.4% had referral to our inpatient palliative care team and4.4% to hospice. 3.8% of patients had documented code status, of these, 78% were DNI/DNR. Family meetings were documented in less than 1% of all patients.186 patients wereidentified with early disease (stage I), these are patients who at time of diagnosis whereeligible for transplant, only 17 (9%) received transplants and none had any end-of-lifeintervention. PC interventions for patients with advanced HCC were infrequent. Specifically,of 141 patients identified as having advanced HCC, defined as either stage III or IV disease,or involvement of the portal vessels; only 15 (10.6%) had any PC intervention. Our singlecenter experience indicates that any PC intervention is an infrequent occurrence, even inadvanced HCC. Given the growing incidence of HCC, and the limited survival despitetherapy, particularly for advanced disease, our findings indicate the need for fuller integrationof palliative care in this population.

Sa1852

The Advantage in Long-Term Survival of Radiofrequency Ablation forHepatocellular Carcinoma Patients: Historical Comparison With EthanolInjectionSatoshi Oeda, Toshihiko Mizuta, Hiroshi Isoda, Takuya Kuwashiro, Shinji Iwane, YasunoriKawaguchi, Iwata Ozaki, Kazuma Fujimoto

Background and Aim: In 1999, we adopted radiofrequency ablation (RFA) for treatment ofsmall hepatocellular carcinoma (HCC). Since this time, the main local therapy for HCC hasshifted from percutaneous ethanol injection (PEI) to RFA. However, little is known onwhether there is a difference in the long-term efficacy between the two methods. Therefore,we historically compared the long-term survival rates of HCC patients treated with RFAwith those treated with PEI. Patients and Methods: Among 213 patients with HCC whowere initially treated with PEI or RFA at Saga Medical School Hospital between 1990 and2004, we examined 190 patients who could be followed up for more than 3 years aftertreatment. They consisted of 98 patients treated with PEI (PEI group) from 1990 to 1999

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