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Hepatocellular Carcinoma Surveillance Rates: Results From a Large Cirrhotic Database Analysis of a VA Medical Center
an impact on survival or tumor response. Methods: We conducted a retrospective analysis of 158 cirrhotic patients who underwent 280 TACE treatments for hepatocellular carcinoma. Cytolysis was defined as an increase of AST value above 100 IU/L with at least doubling of the baseline value within the first five days following treatment. Our primary outcome was the 18 months survival rate following a first treatment of TACE. Secondary outcomes were the radiologic tumor response as measured according to the EASL guidelines (objective response defined as complete or partial response), mean time for disease progression and predictors of cytolysis. Results: Cytolysis was present in 126 patients and absent in 32 at the time of their first treatment. 18 patients died and 29 had a surgical procedure (hepatectomy or transplant) in the cytolysis group versus 8 and 3 respectively in the group without cytolysis. Patients that had a surgical intervention were censored from the survival analysis. The death rate was 14% vs. 25% if cytolysis was present or absent respectively (adjusted hazard ratio of death in cytolysis group 0.7465 ; 95% CI 0.32-1.73, p = 0.49). Regarding the radiologic response, there was no difference in the proportion of treatments resulting in an objective response ( cytolysis: 71/201, cytolysis absent: 18/72, odds-ratio 0.6103 , 95% CI 0.33271.1197, p = 0.1107). The mean time for disease progression was 4.8 months in the cytolysis group and 4.04 months in the group without cytolysis (95% CI 3.8-5.6 vs. 2.86-5.22 months respectively) and was not significantly different between the two groups (p=0.43). In a multivariate analysis, tumor size and AST value before treatment were the only predictors for the incidence of cytolysis. Conclusion: The occurrence of cytolysis after a TACE has no impact on survival at 18 months. It is not associated with a better radiologic response or time for disease progression and has no prognostic significance.
from 2008 until present time, using a combination of cirrhosis-related ICD9 codes and thrombocytopenia of <150K (Table 1). These identified patients were separated into four groups: cirrhotic by ICD9 code, cirrhotics by clinical evaluation but previously undocumented, non-cirrhotics and undetermined patients requiring further workup. The rates of HCC surveillance were then determined in the first two groups and a chi-square analysis was performed between them. Further subgroup analysis was performed to distinguish between the types of physicians initiating the screening. Results: The database comprised a total of 1653 patients, of which 712 were randomly chosen for further evaluation. Of these 712 patients, 111 (15.6%) were categorized as cirrhotic by ICD9 code, while 59 (8.3%) were categorized as clinically cirrhotic. Of these 170 cirrhotics, 92 (57.1%) patients were currently enrolled in an HCC surveillance program as per the VA guidelines. The HCC surveillance rate was 62.6% (67 patients) amongst the patients categorized as cirrhotic by ICD9 code, while it was only 46.3% (25 patients) in previously undocumented cirrhotics. The difference in surveillance rates between these two groups was very significant ( p= 0.048). Among all patients being screened for HCC, the majority were being screened by gastroenterologists (82.4%) and the remainder (17.6%) were screened by primary care physicians. Conclusion: Inspite of societal guidelines, HCC surveillance remains a largely underutilized tool in cirrhotics. Almost half of our patients are not enrolled in a surveillance program. It is imperative that an initiative be taken for improved education and awareness of HCC surveillance guidelines. The instatement of clinical reminders, based on proper ICD9 coding of cirrhosis, might help increase the HCC screening rates to levels comparable to those of colorectal cancer screening. Cirrhosis associated ICD9 codes
Sa1840
AASLD Abstracts
Vitamin D Receptor (VDR) is Expressed in Woodchuck Hepatocellular Cancer (HCC) Roopa Yarlagadda, Richard Cheney, Bud Tennant, Renuka Iyer Introduction: Vitamin D has been shown to have anti-proliferative effects in-vitro in various cell lines and In Vivo models of human cancers including HCC. It exerts the majority of these effects via a nuclear vitamin D receptor (VDR). This receptor is present in various normal tissues related to calcium metabolism as well in several human and rodent tumors and has correlated with responsiveness to the anti-tumor effects of vitamin D and its analogues. The woodchuck is a well characterized model of HCC that develops spontaneously in the context of chronic woodchuck hepatitis B viral (WHV) infection and has been the gold standard for testing various antiviral agents to control human hepatitis B viral infection. To evaluate the anti-proliferative and anti-angiogenic effects of vitamin D in woodchucks we undertook this study to examine the prevalance of VDR in woodchuck HCC cells. Methods: Woodchucks were bred and innoculated at birth with sera from known chronic WHV carrier woodchucks and their WHV titers were serially evaluated. Chronic carriers were followed until ultrasound evidence of tumors in the liver and sacrificed. The expression of nuclear VDR in tumor and adjacent normal liver cells of woodchucks by immunohistochemistry using cross reactive antibodies as no commercial woodhcuck reagents are available. Formalin fixed paraffin sections from 5 woodchuck HCCs and adjacent non-neoplastic liver tissue were cut at 5μm. Antigen retrieval was done. Primary VDR antibody from Affinity Bio Reagents diluted to 2.5μg/ml was used. An isotype-matched control [2.5μg/ml Rat IgG2b] was used on a duplicate slide in place of the primary antibody as a negative control. After counterstain with hematoxyline, the percentage of stained cells for VDR and the intensity of staining for VDR were determined in both tumor cells and adjacent non neoplastic hepatocytes. Results: Median time to development of HCC in chronic WHV carrier woodchucks was 24 months. Strong intensity of nuclear VDR staining was seen in all woodchuck HCCs stained (one USG detected lesion was non malignant). Adjacent non-neoplastic liver tissue showed positive VDR, but intensity was low. The mean percentage of stained cells for VDR was 100% in tumor cells compared to 60% in nonneoplastic cells. Conclusion: Strong nuclear VDR expression is present and can be detected by crossreactive reagents in woodchuck HCC compared to adjacent liver tissue in chronic WHV carrier woodchucks. Our results support evaluating the potential of vitamin D in this highly clinical relevant animal model for prevention and treatment of human HCC. Immunohistochemistry Results of VDR Expression
Sa1842 Observation of Bubbles and Detection of Hepatocytes in the Portal Vein During Radiofrequency Chiaki Kawamoto, Ken-ichi Manaka, Atsushi Yamauchi, Keiko Kaneko, Akiko Miyamoto, Hideji Shimizu, Kyoichi Mizuno [Background and Aims] Radiofrequency ablation (RFA) for hepatocellular carcinoma is considered as a less-invasive therapeutic technique associated with favorable local control. Although RFA was initially expected to decrease the incidence of local recurrence, sporadic cases of unexpected recurrence, such as intrahepatic dissemination, have been described following RFA. Some of these recurrences may be caused by increased intratumoral pressure. During RFA, high echoic areas can be observed by ultrasound in the vessels. Such high echoic areas are thought to represent steam (bubbles) generated by increased intrahepatic pressure in rapidly heated tissue. Therefore, we used an angioscope to observe the bubbles generated during RFA, and examined hepatocytes in the portal vein. [Subjects and Methods] Under general anesthesia, laparotomy was performed on 4 pigs. Bubbles in the portal vein were observed by angioscope using a 16-Fr sheath inserted into the portal vein. The 16-Fr sheath was directly inserted into the portal vein. After inserting a 3.8-mm angioscope into the sheath, a guidewire was used to guide the angioscope to the portal vein, and RFA was performed. A 20-mm LeVeen needle electrode and a cooled-tip RF needle electrode were used for RFA. The down-streaming blood in the vessel attached to the irradiated part was collected and separated by using Ficoll-gradient method, and cultured for 15 hours to examine the existence of intact hepatocytes. [Results] The outflow of bubbles from the RFA site was observed by angioscope at the same time as high echoic areas were observed on ultrasonography. In the fraction of the blood separated by using Ficoll-gradient method, albumin-positive cell clusters were found and were assumedly intact hepatocyte in their morphology. [Conclusions] The present results demonstrate that increased intrahepatic pressure causes bubbles, and the cell cluster was assumedly pushed out into the portal vein from the hepatic lobules by RFA. These results suggested that some risk of dissemination due to RFA exists.
Sa1841 Hepatocellular Carcinoma Surveillance Rates: Results From a Large Cirrhotic Database Analysis of a VA Medical Center Eliezer Weiss, Sabina Kirtich, Pallav K. Parakh, Marina S. Kaufman, Samy McFarlane, Ayse Aytaman
Sa1843 Safety and Efficacy of Loco-Regional Treatment Modalities of Hepatocellular Carcinoma in a Geriatric Population Erik Rahimi, Manhal J. Olaywi, John F. Reinus, Paul J. Gaglio, Harmit S. Kalia, Edward Norkus, Hatef Massoumi
Introduction/Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death world-wide, and the ninth leading cause of cancer related death in the United States. As per 2010 AASLD guidelines HCC surveillance should be performed by ultrasonography at 6 month intervals, while the VA recommendations still include the use of , serum alpha-fetoprotein. This form of surveillance may detect early HCC and increase survival. Despite this, prior studies have demonstrated suboptimal rates of surveillance. Methods: A retrospective database was created by a search of the VA New York Harbor Health System Brooklyn Campus (VA NYHHS BK) electronic medical software (VistA)
Introduction: Older patients with hepatocellular carcinoma (HCC) may be less likely to undergo curative surgeries such as liver transplantation or hepatectomy. Therefore, the locoregional treatments such as Trans Arterial Chemo Embolization (TACE), Radiofrequency Ablation (RFA), Percutaneous Ethanol Injection (PEI) and Selective Internal Radiation (SIRsphere) therapies remain only therapeutic option in many of these patients. The aim of our study was to assess the safety and efficacy of these modalities in an elderly population.
S-923
AASLD Abstracts
from 2008 until present time, using a combination of cirrhosis-related ICD9 codes and thrombocytopenia of <150K (Table 1). These identified patients were separated into four groups: cirrhotic by ICD9 code, cirrhotics by clinical evaluation but previously undocumented, non-cirrhotics and undetermined patients requiring further workup. The rates of HCC surveillance were then determined in the first two groups and a chi-square analysis was performed between them. Further subgroup analysis was performed to distinguish between the types of physicians initiating the screening. Results: The database comprised a total of 1653 patients, of which 712 were randomly chosen for further evaluation. Of these 712 patients, 111 (15.6%) were categorized as cirrhotic by ICD9 code, while 59 (8.3%) were categorized as clinically cirrhotic. Of these 170 cirrhotics, 92 (57.1%) patients were currently enrolled in an HCC surveillance program as per the VA guidelines. The HCC surveillance rate was 62.6% (67 patients) amongst the patients categorized as cirrhotic by ICD9 code, while it was only 46.3% (25 patients) in previously undocumented cirrhotics. The difference in surveillance rates between these two groups was very significant ( p= 0.048). Among all patients being screened for HCC, the majority were being screened by gastroenterologists (82.4%) and the remainder (17.6%) were screened by primary care physicians. Conclusion: Inspite of societal guidelines, HCC surveillance remains a largely underutilized tool in cirrhotics. Almost half of our patients are not enrolled in a surveillance program. It is imperative that an initiative be taken for improved education and awareness of HCC surveillance guidelines. The instatement of clinical reminders, based on proper ICD9 coding of cirrhosis, might help increase the HCC screening rates to levels comparable to those of colorectal cancer screening. Cirrhosis associated ICD9 codes
Sa1840
AASLD Abstracts
Vitamin D Receptor (VDR) is Expressed in Woodchuck Hepatocellular Cancer (HCC) Roopa Yarlagadda, Richard Cheney, Bud Tennant, Renuka Iyer Introduction: Vitamin D has been shown to have anti-proliferative effects in-vitro in various cell lines and In Vivo models of human cancers including HCC. It exerts the majority of these effects via a nuclear vitamin D receptor (VDR). This receptor is present in various normal tissues related to calcium metabolism as well in several human and rodent tumors and has correlated with responsiveness to the anti-tumor effects of vitamin D and its analogues. The woodchuck is a well characterized model of HCC that develops spontaneously in the context of chronic woodchuck hepatitis B viral (WHV) infection and has been the gold standard for testing various antiviral agents to control human hepatitis B viral infection. To evaluate the anti-proliferative and anti-angiogenic effects of vitamin D in woodchucks we undertook this study to examine the prevalance of VDR in woodchuck HCC cells. Methods: Woodchucks were bred and innoculated at birth with sera from known chronic WHV carrier woodchucks and their WHV titers were serially evaluated. Chronic carriers were followed until ultrasound evidence of tumors in the liver and sacrificed. The expression of nuclear VDR in tumor and adjacent normal liver cells of woodchucks by immunohistochemistry using cross reactive antibodies as no commercial woodhcuck reagents are available. Formalin fixed paraffin sections from 5 woodchuck HCCs and adjacent non-neoplastic liver tissue were cut at 5μm. Antigen retrieval was done. Primary VDR antibody from Affinity Bio Reagents diluted to 2.5μg/ml was used. An isotype-matched control [2.5μg/ml Rat IgG2b] was used on a duplicate slide in place of the primary antibody as a negative control. After counterstain with hematoxyline, the percentage of stained cells for VDR and the intensity of staining for VDR were determined in both tumor cells and adjacent non neoplastic hepatocytes. Results: Median time to development of HCC in chronic WHV carrier woodchucks was 24 months. Strong intensity of nuclear VDR staining was seen in all woodchuck HCCs stained (one USG detected lesion was non malignant). Adjacent non-neoplastic liver tissue showed positive VDR, but intensity was low. The mean percentage of stained cells for VDR was 100% in tumor cells compared to 60% in nonneoplastic cells. Conclusion: Strong nuclear VDR expression is present and can be detected by crossreactive reagents in woodchuck HCC compared to adjacent liver tissue in chronic WHV carrier woodchucks. Our results support evaluating the potential of vitamin D in this highly clinical relevant animal model for prevention and treatment of human HCC. Immunohistochemistry Results of VDR Expression
Sa1842 Observation of Bubbles and Detection of Hepatocytes in the Portal Vein During Radiofrequency Chiaki Kawamoto, Ken-ichi Manaka, Atsushi Yamauchi, Keiko Kaneko, Akiko Miyamoto, Hideji Shimizu, Kyoichi Mizuno [Background and Aims] Radiofrequency ablation (RFA) for hepatocellular carcinoma is considered as a less-invasive therapeutic technique associated with favorable local control. Although RFA was initially expected to decrease the incidence of local recurrence, sporadic cases of unexpected recurrence, such as intrahepatic dissemination, have been described following RFA. Some of these recurrences may be caused by increased intratumoral pressure. During RFA, high echoic areas can be observed by ultrasound in the vessels. Such high echoic areas are thought to represent steam (bubbles) generated by increased intrahepatic pressure in rapidly heated tissue. Therefore, we used an angioscope to observe the bubbles generated during RFA, and examined hepatocytes in the portal vein. [Subjects and Methods] Under general anesthesia, laparotomy was performed on 4 pigs. Bubbles in the portal vein were observed by angioscope using a 16-Fr sheath inserted into the portal vein. The 16-Fr sheath was directly inserted into the portal vein. After inserting a 3.8-mm angioscope into the sheath, a guidewire was used to guide the angioscope to the portal vein, and RFA was performed. A 20-mm LeVeen needle electrode and a cooled-tip RF needle electrode were used for RFA. The down-streaming blood in the vessel attached to the irradiated part was collected and separated by using Ficoll-gradient method, and cultured for 15 hours to examine the existence of intact hepatocytes. [Results] The outflow of bubbles from the RFA site was observed by angioscope at the same time as high echoic areas were observed on ultrasonography. In the fraction of the blood separated by using Ficoll-gradient method, albumin-positive cell clusters were found and were assumedly intact hepatocyte in their morphology. [Conclusions] The present results demonstrate that increased intrahepatic pressure causes bubbles, and the cell cluster was assumedly pushed out into the portal vein from the hepatic lobules by RFA. These results suggested that some risk of dissemination due to RFA exists.
Sa1841 Hepatocellular Carcinoma Surveillance Rates: Results From a Large Cirrhotic Database Analysis of a VA Medical Center Eliezer Weiss, Sabina Kirtich, Pallav K. Parakh, Marina S. Kaufman, Samy McFarlane, Ayse Aytaman
Sa1843 Safety and Efficacy of Loco-Regional Treatment Modalities of Hepatocellular Carcinoma in a Geriatric Population Erik Rahimi, Manhal J. Olaywi, John F. Reinus, Paul J. Gaglio, Harmit S. Kalia, Edward Norkus, Hatef Massoumi
Introduction/Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death world-wide, and the ninth leading cause of cancer related death in the United States. As per 2010 AASLD guidelines HCC surveillance should be performed by ultrasonography at 6 month intervals, while the VA recommendations still include the use of , serum alpha-fetoprotein. This form of surveillance may detect early HCC and increase survival. Despite this, prior studies have demonstrated suboptimal rates of surveillance. Methods: A retrospective database was created by a search of the VA New York Harbor Health System Brooklyn Campus (VA NYHHS BK) electronic medical software (VistA)
Introduction: Older patients with hepatocellular carcinoma (HCC) may be less likely to undergo curative surgeries such as liver transplantation or hepatectomy. Therefore, the locoregional treatments such as Trans Arterial Chemo Embolization (TACE), Radiofrequency Ablation (RFA), Percutaneous Ethanol Injection (PEI) and Selective Internal Radiation (SIRsphere) therapies remain only therapeutic option in many of these patients. The aim of our study was to assess the safety and efficacy of these modalities in an elderly population.
S-923
AASLD Abstracts