- Email: [email protected]
S1280 Ethnicity, Alcohol Consumption, and Cigarette use as Predictors for Hepatocellular Carcinoma: A Prospective Study
US was falsely negative and CT found a lesion, the mean alpha fetoprotein (AFP) value was 32,325 ng/mL. This included 2 patients whose AFP values were greater than 400 ng/mL (1,136 and 257,115 ng/mL), 4 patients whose AFP values were greater than 20 and less than 400 (28, 50, 65, and 185 ng/mL), and 2 patients with AFP values less than 20 (3.6 and 19 ng/mL). In 125 patients with a true negative US the mean AFP was 17.14 ng/mL. This group had only 12 patients, or 9.6%, with an AFP greater than 20 ng/mL, and only 1 who had an AFP greater than 400 ng/mL. In the entire population of patients who met our sequencing criteria, the positive predictive value of US for detecting HCC was 96.3%, while the negative predictive value was 94.0%. Combining US with the AFP level, and using a cutoff of 20 ng/mL, the sensitivity was increased to 87.5%. In this series of 160 patients, only 2 patients had a negative US and a normal AFP level and still had HCC. Conclusion: The data suggests that screening for HCC in high risk populations can effectively be performed by using US as the initial screening exam. In this series alone, 74 CT or MRI studies could have been avoided with the combined use of US and AFP for screening. However, 12 unnecessary CT or MRI studies would also have been performed. In combination with regular monitoring of AFP levels, US can eliminate more expensive imaging studies until confirmation is necessary, thus reducing the overall cost of medical monitoring for patients in HCC screening populations.
The Effect of Type 2 Diabetes Mellitus on Sustained Virologic Response Rates for Hepatitis C Treatment Among Urban Patients at a Safety-Net Hospital Ashley L. Reid, Melissa K. Osborn, Akilah Strawder, Shelly-Ann Fluker, Lesley Miller Purpose: Prior studies suggest that there is an intimate relationship between glucose abnormalities and hepatitis C virus (HCV) infection. Chronic HCV infection is associated with an increased risk of developing type 2 diabetes mellitus (DM2). There is also evidence that DM2 portends a poor virological response to treatment for HCV infection. The objective of this study was to compare the sustained virologic response (SVR) rates for hepatitis C treatment of patients with and without DM2 at a large, urban, hepatitis C clinic (Liver Clinic). Methods: A retrospective chart review was conducted of all patients with at least one visit to the Liver Clinic at Grady Memorial Hospital in Atlanta, Georgia from May 2002 through December 2007. A total of 870 charts were reviewed. Data was collected on patient demographics, HCV genotype, HCV treatment response, and medical co-morbidities, including DM2. From the 870 charts reviewed, 113 patients had been treated with pegylated interferon and ribavirin. Twenty-six of the treated patients had DM2. Charts of treated DM2 patients were reviewed for pre-treatment HgbA1c values. For treated patients, the SVR rate of the DM2 patients was compared to that for non-DM2 patients. Statistical analysis was performed using SAS. Results: Patients with DM2 had a 38% SVR rate compared to 28% for the non-DM2 patients. Eighty-eight percent of DM2 cohort had genotype 1 HCV compared to 85% of the non-DM2 cohort. The DM2 cohort had 61% African Americans, compared to 70% in the non-DM2 cohort. The mean weight for the DM2 and non-DM2 cohorts was 88 and 84 kgs respectively. The mean HgbA1c in the DM2 group before treatment was 6.24%. Conclusion: Prior studies indicate that DM2 patients have significantly lower SVR rates than those without diabetes (16% versus 45%). It is therefore unexpected that the treated DM2 patients in this population had a superior SVR rate (38%) compared to the treated non-DM2 patients (28%,). The patients with DM2 in this cohort achieved a higher SVR rate despite having a higher percentage of genotype 1 patients and a higher mean weight than the non-DM2 patients, although this did not reach statistical significance. Factors that may contribute to these findings include a clinic protocol that approves only wellcontrolled DM2 patients for hepatitis C treatment (as evidenced by the low pre-treatment hemoglobin A1C). Also, in this patient population, medication non-adherence is a major barrier to disease control. It is likely that low HgbA1c serves as a marker for overall adherence to therapy, including to hepatitis C treatment, in the DM2 patients.
S1279 Treatment of Neoplastic Stenosis of the Biliary Tract With Self Expandable Metal Stents: A Retrospective Study of 211 Consecutive Procedures Comparaison of Percutaneous Versus Endoscopic Drainage Romain Legros, Leila Kanafi, Anne Le Sidaner, Sébastien Seillan, Paul Carrier, Alexandre Giraud, Virginie Valgueblasse, Francois Cessot, Denis Sautereau Introduction: Few studies compare the endoscopic and the percutaneous technique for drainage of neoplastic stenosis of the biliary tract with self expendable metal stents. We compared the clinical outcomes of these 2 methods of biliary decompression in these patients. Patients and methods: We selected procedures from 2005 to 2008. They received percutaneous or endoscopic treatment after antibioprophylaxy by cefalolizine. Wallstent®, Wallflex® or Bonastent® were used for the endoscopic drainage. Luminexx® were used for the percutaneous drainage. Data concerning every patient and every procedure were reviewed retrospectively. A same patient could have several procedures. Results: Two hundred eleven consecutive procedures were enrolled, 107 with percutaneous drainage and 104 with endoscopic drainage. In procedures led with percutaneous 62 concerned hilar stenosis and 44 concerned common bile duct. In procedures led with endoscopy, 23 concerned hilia stenosis and 81 concerned common bile duct. The main etiologies (63 %) were the pancreatic cancer and the cholangiocarcinoma. The patients were older in procedures led with endoscopic treatment. Score ASA, number of metastatic patients and rate of anatomopathological samples were more raised in the group treated with percutaneous technique. The rates of technical and clinical successes were comparable for two techniques. On the other hand there were more immediate complications for the percutaneous drainage (35% versus 8% with p=0,0002) and mortality in 30 days was more high (28% versus 6% with p=0,02). Main complication in the two groups was the angiocholitis. They were significantly higher in the percutaneous group (p=0,001) and three of them had lethal issue. The comparaison of percutaneous versus endoscopic technique for only hilar stenosis or only common bile duct stenosis show more immediate complications for the percutaneous drainage with respectively p=0,0073 and p=0,0075. There were no differences for the rates of technical and clinical successes regardless of the location. Stent patency and total days hospitalization were similar in the two study groups. Discussion: In front of a weaker morbidity for a rate of success identical to the percutaneous drainage, it seems that the endoscopic treatment should be used in first intention, including in hilar stenosis. In case of failure the percutaneous drainage can be used in 2nd intention.
S1277 Serum Immunoglobulins in Patients With Chronic Viral Hepatitis B and C Prior to Any Therapy Paul B. Southern, Melpomeni Rompola, Chrysoula Fragkopoulou, Sulleman Moreea Introduction: The significance of moderate polyclonal gammaglobulinemia which is a common finding in patients with chronic hepatitis B and C has not been fully explored. Aims: To analyse the immunoglobulin levels (IgG, IgA and IgM g/L) and non-organ-specific autoantibody (NOSA) status in patients with chronic hepatitis B (HBV) and C(HCV) and to study any differences between ethnic groups. Methods: The following data from our viral hepatitis databases was obtained for patients prior to any therapy: demographics, ethnicity, Ig G/A/ M levels and NOSA. Results: Data from 682 patients-413 HCV(M=251, F=159 mean age 39.9), 269 HBV (M=143, F=126, mean age 39.1) showed that IgG was more commonly elevated in HCV vs HBV: 49.2% vs 25.7% IgG (p<0.05). Both IgG and IgM were also more significantly elevated in HCV vs HBV: 16.6g/L vs 14.4g/L for IgG (p<0.05) and 1.63g/L vs 1.14 g/L for IgM (p<0.05). Mean IgG levels were compared by race (African (14.7g/L), South-East Asian (16.5g/L), Chinese (14.04g/L), Caucasian (14.5g/L)) and significant differences were found between South-East Asians and Chinese (p=0.028) and also white Caucasians (P<0.005). Mean IgM levels when compared by race (African (1.06g/L), South-East Asian (1.32g/L), Chinese (1.05g/L), Caucasian (1.82g/L)) also showed significant differences between Caucasians and Africans (p<0.005), South-East Asians (p<0.005) and Chinese (p<0.005). When immunoglobulins were examined using sex, the significant findings were for IgG and IgM levels in HCV (IgG 16.1g/L males, vs. 17.6g/L females (p=0.003) and IgM 1.53g/L males vs. 1.81g/L females (p=0.006)). In HBV IgA levels (2.31g/L female vs. 2.68g/ L male (p=0.002) and IgM 1.23g/L female vs. 1.07g/L male (p=0.039) were found to be significant. NOSA status examined in 117 patients (17.2%) were found to be significantly positive for HCV vs HBV (19.9% vs 13% - p<0.05). Conclusion: This study shows that patients are significantly more likely to have abnormal IgG and M levels with HCV than HBV and there is also an ethnic and age difference. It is unclear whether these differences are due to a cause (immunoglobulins are fibrogenic) or an effect (fibrosis is immunogenic).
S1280 Ethnicity, Alcohol Consumption, and Cigarette use as Predictors for Hepatocellular Carcinoma: A Prospective Study Nghi B. Ha, Nghiem B. Ha, Aijaz Ahmed, Walid Ayoub, Tami Daugherty, Glen A. Lutchman, Gabriel Garcia, Allen D. Cooper, Peter B. Gregory, Emmet B. Keeffe, Mindie H. Nguyen PURPOSE: Data on alcohol and/or cigarette use as risk factors for hepatocellular carcinoma (HCC) has been conflicting and inconclusive. In the case of alcohol, it is not clear whether the effect is due to alcohol itself or alcohol-related cirrhosis. Thus, we proposed a study to examine alcohol use and cigarette use as risk factors associated with HCC in a large casecontrol study with a prospective questionnaire. METHODS: We conducted a case-control study of 984 patients: 253 HCC cases and 731 controls without HCC enrolled by convenience sampling between February 2001 and October 2009 at a university liver clinic in California. The ethnic make-up of the total study population was as follows: 42% Whites, 14% Hispanics, 3% African-Americans, 39% Asian Americans and 2% Others. Risk factors were examined through medical records and a prospective 12-page risk factor questionnaire administered by a research coordinator. All patients gave written informed consent. Alcohol use was calculated by cumulative grams of alcohol consumed up to the time of this study. Tobacco use was calculated by cumulative pack(s) of cigarette consumed up to the time of this study. Risk factors were evaluated using multivariate logistic regression. RESULTS: Cases were older (60±11 vs. 52±11, p<0.0001), more likely to be male (81% vs. 61.2%, p<0.0001), and more likely to have cirrhosis (85.6% vs. 73.6%, p<0.0001). Patients with cirrhosis consumed a significantly greater average amount of alcohol in total grams (log10) (5.6 vs. 4.9, p<0.00001) and used a significantly greater average amount of tobacco in cumulative packs (917 vs. 333, p=0.004). Cases had significantly greater lifetime tobacco use (1,202 vs. 635 packs, p=0.006). There were no significant differences in proportions of patients with family history of HCC or exposure to vinyl chloride among cases and controls. In multivariate logistic regression also inclusive of CPT score, etiologies of primary liver disease, and alcohol, significant independent predictors for HCC included age over 40 (OR=6.3, p= 0.001), male sex (OR=2.6, p<0.0001), presence of cirrhosis (OR=3.7, p<0.001), cumulative tobacco use > 1000 packs (OR=1.9, p=0.02), and Asian ethnicity compared to Whites and
S1278 Use of Ultrasound as the Initial Imaging Exam for Hepatocellular Carcinoma in High Risk Populations Jason B. Welch, Richa Shukla, Nnenna L. Igbo, Ashwani K. Singal, Joao F. Kazan-Tannus, Roger D. Soloway Background and Aims: Detection of Hepatocellular Carcinoma (HCC) in high risk populations has traditionally involved the use of ultrasound (US), followed by computed tomography (CT) or Magnetic Resonance Imaging (MRI) for confirmation of suspected lesions. No studies to date have specifically compared the accuracy of US in detecting HCC with that of CT or MRI. The aim of our study was to determine, retrospectively, in an unselected population of patients with cirrhosis, if an initial US could be as accurate as a subsequent CT or MRI in detecting HCC. Methods: We conducted a search of cases in which screening was performed with US and followed by CT or MRI within 6 months. Any patient with known HCC prior to a screening US was excluded. 1600 consecutive patients from 2004-2007 who had an initial US were reviewed, of which 160 fulfilled this sequence. This group included 34 cases of suspected HCC. Results: Of these 34 patients, 26 were correctly identified as having HCC by abdominal US, representing a sensitivity of 76.5%. The specificity for US in the detection of HCC was found to be 99.2% (1 false positive). In 8 cases where
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Hispanics (OR=2.9, p<0.0001). CONCLUSIONS: Cumulative tobacco use of > 1000 packs was an independent predictor for HCC but not alcohol consumption. Other significant independent predictors for HCC were Asian ethnicity, age over 40, male sex, and cirrhosis. Patients with risk factors for HCC should be strongly advised against tobacco use.
men and 13 women, 24 rectal cancer and 17 colon cancer, 61.4 years old) who underwent liver resection from September 2001 to January 2008. All patients underwent complete resection of the primary carcinoma with lymph nodes dissection. Radio frequency ablation therapy was performed by use of cool tip 2 cm or 3 cm. The duration of ablation was 6 minutes each time. Patient survival calculated by Kaplan-Meier method, complication, complication and hopital stay were compared between each group. [Results] The average diameter and number of liver metastasis was 2.8 cm, 2.5 in RF group and 3.8 cm, 1.5 in liver resection group (no significant difference). There was no significant difference about the number of therapy (1.53 (RF group) vs. 1.08 (liver resection group)). We found significantly shorter hospital stay among RF group patients than that among liver resection group (7.5 vs 27.9 days). The average follow-up time was 2.9 years in RF group and 2.8 years in liver resection group. No significant difference was found about 6 years patient survival between two groups (31.7 % in RF group vs. 31.1 % in liver resection group). There were one complication (5.6 %) in RF group (subserosal hematoma) and 4 (9.8 %) in liver resection group (2 bile leakage, one intestinal obstruction, one wound infection). No additional surgery was necessary for those patients with complication. There was no difference about the contents of chemotherapy after the treatment for liver metastasis between both of groups. [Discussion] Radio frequency ablation therapy can be safely performed and is effective treatment for liver metastasis from colorectal carcinoma.
S1281 Evaluation of the Effects of Molecular Target Agents by Tumor Marker Doubling Time Kenichiro Enooku, Ryosuke Tateishi, Fumihiko Kanai, Haruhiko Yoshida, Koji Uchino, Toru Arano, Eriko Goto, Ryota Masuzaki, Noriyo Yamashiki, Tadashi Goto, Shuichiro Shiina, Masao Omata, Kazuhiko Koike BACKGROUND/AIMS For the evaluation of response to cytostatic agents, determination of changes in tumor growth speed seems to be essential. RECIST, which lacks the dimension of time, may not be particularly suitable for these agents. The aim of this study is to elucidate the usefulness of tumor marker doubling time (DT) in the evaluation of response to a molecular target agent. PATIENTS AND METHODS A total of 25 patients with advanced HCC participated in the phase I/II clinical trial of TSU-68, a novel tyrosine kinase inhibitor of VEGF. We enrolled 15 patients whose alpha-fetoprotein (AFP) or des-gamma-carboxyprothrombin (DCP) showed exponential increase during wash-out phase before TSU administration. We analyzed the relationship between tumor marker DT and tumor volume DT measured on two CT examinations before the commencement of TSU-68 administration. Next, tumor marker DT in the first 8 weeks of TSU-68 administration was similarly calculated, and compared with DT before TSU-68 administration. DT should be elongated, or turn negative, if TSU-68 was effective. The evaluation based on tumor marker DT was compared with RECIST. Lastly, tumor marker DT after the cessation of TSU-68 was calculated and compared with DT in 4 weeks immediately before the cessation. RESULTS DT of tumor marker level and that of tumor volume before TSU-68 administration were almost identical (R2=0.94, P<0.001). The evaluation based on tumor marker DT comparison between before and during TSU-68 administration and that based on RECIST were compatible in most cases (12/15); discordance was observed in 3 cases judged as disease progression by RECIST due to substantial tumor necrosis without volume shrinkage or appearance of new lesions in spite of apparent effects on target lesions. In these cases DT elongation was observed, which suggested cytostatic effect of TSU-68. Tumor marker DT after the cessation of TSU86 administration was evaluated in 4 cases, where DT was shortened after the cessation. CONCLUSION Serum tumor marker levels can be used to evaluate viable tumor burden irrespective of the presence of tumor necrosis, which may compromise radiographic evaluation. This may be applicable to the evaluation of response to chemotherapy with cytostatic agents in particular.
S1284 Predictive Value of FDG PET-CT for Early Recurrence in Surgical Resection Against Hepatocellular Carcinoma Atsushi Hiraoka, Kojiro Michitaka, Masao Miyagawa, Hideki Kawasaki, Satoshi Hidaka, Takahide Uehara, Aki Hasebe, Yasunao Miyamoto, Tomoyuki Ninomiya, Hironori Ochi, Masashi Hirooka, Yoshimasa Yamashita, Norio Horiike, Yoichi Hiasa, Bunzo Matsuura, Morikazu Onji Background/Aim: The clinical efficacy of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) Positron Emission Tomography (PET) computed tomography (CT) for hepatocellular carcinoma (HCC) has not been established. Hepatic resection for HCC has been performed widely in Japan due to lack of donor for liver transplantation. Early recurrence of HCC has been known as a poor prognostic factor for death. Herein, we associated the predictive value of PET-CT for early recurrence in hepatic resection. Methods: From April 2006 to October 2009, 53 patients with naïve HCC who were examined by PET-CT before hepatic resection were enrolled. Accumulations of FDG [standardized uptake value (SUVmax)] in HCC and in liver, and the ratio of SUVmax (HCC/liver) (R-SUV) were calculated. Patients were divided into high R-SUV (1.5≤, H-group, n=19) and low R-SUV (1.5>, L-group, n=34). We evaluated prognostic factors for early recurrence after resection. Results: One was tumor node metastasis (TNM) stage I, 35 were II, 14 were III, and 3 were IV. Though, the frequencies with the high levels of protein induced by vitamin K absence or antagonist II (PIVKA-II: 200mAU/ ml<) and fucosylated alfa-fetoprotein (AFP) (AFP-L3: 15%<) were larger in H-group (52.9 vs 21.1%, 38.2 vs 10.5%, P<0.01), whereas there were no significant differences in the frequencies with high levels of AFP (100ng/ml<) and with large tumor diameter (5cm<), Child-Pugh class, the number of tumor, and TNM stage between both groups. The recurrentfree rate of L-group were higher than H-group (1- and 2-year recurrent-free rate: 100 and 67% vs 67 and 17%, respectively, P<0.01). PIVKA-II (200mAU/ml<), AFP-L3 (15%<), and total bilirubin (2mg/dl), and the high R-SUV (1.5≤) were the risk factors for early recurrence in univariate analysis (P<0.05, respectively). In multivariate analysis, high R-SUV (1.5≤) was the only risk factor (P<0.05). In pathological analysis, all were typical HCC. HCC nodules with Edmondson III showed higher R-SUV (3.0±1.8) than those with I and II (1.4±0.3 and 1.9±0.9) (P<0.01). Nodules with micro vascular invasion (vp) (+), micro intrahepatic metastasis (im) (+), and the nonboundary type nodules (single nodular type with extranodular growth, confluent multinodular or invasive type) showed higher R-SUV than those with vp (-), im (-), or the boundary type (vaguely nodular or single nodular type) (3.6±2.4 vs 2.0±0.9, 3.5±2.3 vs 1.9±0.8, 2.9±1.8 vs 1.6±0.5, respectively, P<0.01). Conclusion: HCC with high R-SUV (1.5≤) related to early recurrence of HCC after resection. RSUV had relation to pathological findings. R-SUV was found to be a useful prediction marker for the early recurrence of HCC after resection.
S1282 Rate of Stage Transition From Early to Advanced Hepatocellular Carcinoma Toru Arano, Ryosuke Tateishi, Shuichiro Shiina, Koji Uchino, Keniciro Enooku, Eriko Goto, Ryota Masuzaki, Hayato Nakagawa, Yuji Kondo, Noriyo Yamashiki, Tadashi Goto, Hajime Fujie, Masao Omata, Haruhiko Yoshida, Kazuhiko Koike Background and Aims: In spite of advances in diagnosis and treatment of hepatocellular carcinoma (HCC), recurrence of HCC is very frequent even after curative treatments, resulting in uncontrollable cancer or hepatic failure, and long-term prognosis of HCC remains poor. We analyzed progression rates from early stage HCC to terminal stage and death, and simulated expected effects of intervention in each stage. Methods: Among 666 patients with HCC who received radiofrequency ablation at the authors' hospital between 1999 and 2004, 359 patients who presented HCC not more than 3 in number and not larger than 3 cm in diameter were enrolled. Clinical stages after initial treatment were divided into A (n ≦ 3 and size ≦ 3 cm), B (n > 3 or size > 3cm), C (with extrahepatic metastasis or vascular invasion) according to BCLC staging classification. The progression rates between stages were calculated by using competing event model, and temporal transition between stages was simulated based on a Markov chain model. Results: Enrolled patients consists of 232 males and 127 females (mean ± SD age, 68 ± 8.1 years; mean tumor size, 2.1 ± 0.5 cm; mean tumor number, 1.5 ± 0.7; Child A/B, 246/111; HCV/HBV, 290/31). By fitting an exponential model to the results of competing event analysis, the annual rate of stage transition from A to B, A to C and A to death were calculated as 6.3, 1.3% and 3.5%, respectively. Among those who advanced to stage B, the annual rates of transition to stage C and death were 16.1% and 14.2%, respectively. The annual rate of transition from C to death was 72%. When the analysis was performed with respect to liver function (Child A vs. B/C), significant difference was observed in the rates of transition from A to death (2.4% vs. 7.5%). By fitting Markov chain model, 3- and 5-year survival rates of Child A vs. B/C patients were estimated as 88.4% and 76.4% vs. 75.7% and 59.1%, respectively. When compared to actual data (89.1% and 71.4% for Child A and 71.7% and 51.8% for Child B/C), the survival rates were slightly overestimated at 5 years. The effects of a treatment that prolongs the duration of stage A, B and C by 1.5 times were estimated as increase in 5-year survival rates of 2.6%, 0.8% and 1.5%, respectively. Conclusion: To divide the complicated clinical course of HCC into several stages, we can evaluate the effects of treatments such as recurrence suppression, adjuvant therapy or molecular targeting therapy on the overall survival independently.
S1285 Type 2 Diabetes Mellitus is Associated With Hepatic Fibrosis in Chronic Hepatitis C Patients in Taiwan Chia-Yen Dai, Jee-Fu Huang, Ming-Yen Hsieh, Nai-Jen Hou, Zu-Yau Lin, Shinn-Cherng Chen, Liang-Yen Wang, Wan-Long Chuang, Ming-Lung Yu Background and aims: Type 2 diabetes mellitus (DM) is one of the extrahepatic manifestations of hepatitis C virus (HCV) infection. The aims of the study were to elucidate the association between DM and severity of fibrosis and the associations between these parameters and the virological characteristics in CHC patients in Taiwan. Methods: A large scale study enrolling CHC patients with biopsy-proven chronic hepatitis was conducted. Serum HCV RNA, HCV RNA levels and HCV genotypes 1a, 1b, 2a, 2b and 3a were determined. The liver histology was assessed using the modified histologic activity index (HAI) scoring system and steatosis was quantified as the percentage of hepatocytes that contained fat droplets. Results: We enrolled 927 CHC patients (547 males, mean age: 51.0 years, 506 with type 1 infection) with 37.8% and 27.6% patients having hepatic steatosis and severe fibrosis (F3-4), respectively. DM was diagnosed in 19.2% patients. Multivariate logistic regression analyses showed that male gender, a higher ALT level, the presence of steatosis, severe fibrosis (F3-4) and a higher BMI were independent factors associated with DM. Variables independently associated with steatosis were presence of DM, a higher necroinflammatory score, and a higher BMIin CHC patients. Presence of DM, a higher necroinflammatory score, and a higher BMI were independent factors associated with severe fibrosis in CHC patients. The virologic characteristics including HCV genotype and HCV RNA levels were not associated with DM, severe fibrosis and steatosis in CHC patients. Conclusion: we found in the large scale study that DM was associated with histological characteristics of steatosis and severe fibrosis. DM, BMI and necroinflammation activity are factors commonly associated both steatosis and severe
S1283 Effect of Radio Frequency Ablation Therapy for Liver Metastasis From Colorectal Cancer Masaru Hirata [Background] We compared the complication and patient survival between radio frequency ablation therapy and liver resection for liver metastasis from colorectal cancer. [Patients and Method] Patients consisted of 18 cases (12 men and 6 women, 9 rectal cancer and 9 colon cancer, 63.1 years old) who underwent radio frequency ablation therapy and 41 cases (28
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The Effect of Type 2 Diabetes Mellitus on Sustained Virologic Response Rates for Hepatitis C Treatment Among Urban Patients at a Safety-Net Hospital Ashley L. Reid, Melissa K. Osborn, Akilah Strawder, Shelly-Ann Fluker, Lesley Miller Purpose: Prior studies suggest that there is an intimate relationship between glucose abnormalities and hepatitis C virus (HCV) infection. Chronic HCV infection is associated with an increased risk of developing type 2 diabetes mellitus (DM2). There is also evidence that DM2 portends a poor virological response to treatment for HCV infection. The objective of this study was to compare the sustained virologic response (SVR) rates for hepatitis C treatment of patients with and without DM2 at a large, urban, hepatitis C clinic (Liver Clinic). Methods: A retrospective chart review was conducted of all patients with at least one visit to the Liver Clinic at Grady Memorial Hospital in Atlanta, Georgia from May 2002 through December 2007. A total of 870 charts were reviewed. Data was collected on patient demographics, HCV genotype, HCV treatment response, and medical co-morbidities, including DM2. From the 870 charts reviewed, 113 patients had been treated with pegylated interferon and ribavirin. Twenty-six of the treated patients had DM2. Charts of treated DM2 patients were reviewed for pre-treatment HgbA1c values. For treated patients, the SVR rate of the DM2 patients was compared to that for non-DM2 patients. Statistical analysis was performed using SAS. Results: Patients with DM2 had a 38% SVR rate compared to 28% for the non-DM2 patients. Eighty-eight percent of DM2 cohort had genotype 1 HCV compared to 85% of the non-DM2 cohort. The DM2 cohort had 61% African Americans, compared to 70% in the non-DM2 cohort. The mean weight for the DM2 and non-DM2 cohorts was 88 and 84 kgs respectively. The mean HgbA1c in the DM2 group before treatment was 6.24%. Conclusion: Prior studies indicate that DM2 patients have significantly lower SVR rates than those without diabetes (16% versus 45%). It is therefore unexpected that the treated DM2 patients in this population had a superior SVR rate (38%) compared to the treated non-DM2 patients (28%,). The patients with DM2 in this cohort achieved a higher SVR rate despite having a higher percentage of genotype 1 patients and a higher mean weight than the non-DM2 patients, although this did not reach statistical significance. Factors that may contribute to these findings include a clinic protocol that approves only wellcontrolled DM2 patients for hepatitis C treatment (as evidenced by the low pre-treatment hemoglobin A1C). Also, in this patient population, medication non-adherence is a major barrier to disease control. It is likely that low HgbA1c serves as a marker for overall adherence to therapy, including to hepatitis C treatment, in the DM2 patients.
S1279 Treatment of Neoplastic Stenosis of the Biliary Tract With Self Expandable Metal Stents: A Retrospective Study of 211 Consecutive Procedures Comparaison of Percutaneous Versus Endoscopic Drainage Romain Legros, Leila Kanafi, Anne Le Sidaner, Sébastien Seillan, Paul Carrier, Alexandre Giraud, Virginie Valgueblasse, Francois Cessot, Denis Sautereau Introduction: Few studies compare the endoscopic and the percutaneous technique for drainage of neoplastic stenosis of the biliary tract with self expendable metal stents. We compared the clinical outcomes of these 2 methods of biliary decompression in these patients. Patients and methods: We selected procedures from 2005 to 2008. They received percutaneous or endoscopic treatment after antibioprophylaxy by cefalolizine. Wallstent®, Wallflex® or Bonastent® were used for the endoscopic drainage. Luminexx® were used for the percutaneous drainage. Data concerning every patient and every procedure were reviewed retrospectively. A same patient could have several procedures. Results: Two hundred eleven consecutive procedures were enrolled, 107 with percutaneous drainage and 104 with endoscopic drainage. In procedures led with percutaneous 62 concerned hilar stenosis and 44 concerned common bile duct. In procedures led with endoscopy, 23 concerned hilia stenosis and 81 concerned common bile duct. The main etiologies (63 %) were the pancreatic cancer and the cholangiocarcinoma. The patients were older in procedures led with endoscopic treatment. Score ASA, number of metastatic patients and rate of anatomopathological samples were more raised in the group treated with percutaneous technique. The rates of technical and clinical successes were comparable for two techniques. On the other hand there were more immediate complications for the percutaneous drainage (35% versus 8% with p=0,0002) and mortality in 30 days was more high (28% versus 6% with p=0,02). Main complication in the two groups was the angiocholitis. They were significantly higher in the percutaneous group (p=0,001) and three of them had lethal issue. The comparaison of percutaneous versus endoscopic technique for only hilar stenosis or only common bile duct stenosis show more immediate complications for the percutaneous drainage with respectively p=0,0073 and p=0,0075. There were no differences for the rates of technical and clinical successes regardless of the location. Stent patency and total days hospitalization were similar in the two study groups. Discussion: In front of a weaker morbidity for a rate of success identical to the percutaneous drainage, it seems that the endoscopic treatment should be used in first intention, including in hilar stenosis. In case of failure the percutaneous drainage can be used in 2nd intention.
S1277 Serum Immunoglobulins in Patients With Chronic Viral Hepatitis B and C Prior to Any Therapy Paul B. Southern, Melpomeni Rompola, Chrysoula Fragkopoulou, Sulleman Moreea Introduction: The significance of moderate polyclonal gammaglobulinemia which is a common finding in patients with chronic hepatitis B and C has not been fully explored. Aims: To analyse the immunoglobulin levels (IgG, IgA and IgM g/L) and non-organ-specific autoantibody (NOSA) status in patients with chronic hepatitis B (HBV) and C(HCV) and to study any differences between ethnic groups. Methods: The following data from our viral hepatitis databases was obtained for patients prior to any therapy: demographics, ethnicity, Ig G/A/ M levels and NOSA. Results: Data from 682 patients-413 HCV(M=251, F=159 mean age 39.9), 269 HBV (M=143, F=126, mean age 39.1) showed that IgG was more commonly elevated in HCV vs HBV: 49.2% vs 25.7% IgG (p<0.05). Both IgG and IgM were also more significantly elevated in HCV vs HBV: 16.6g/L vs 14.4g/L for IgG (p<0.05) and 1.63g/L vs 1.14 g/L for IgM (p<0.05). Mean IgG levels were compared by race (African (14.7g/L), South-East Asian (16.5g/L), Chinese (14.04g/L), Caucasian (14.5g/L)) and significant differences were found between South-East Asians and Chinese (p=0.028) and also white Caucasians (P<0.005). Mean IgM levels when compared by race (African (1.06g/L), South-East Asian (1.32g/L), Chinese (1.05g/L), Caucasian (1.82g/L)) also showed significant differences between Caucasians and Africans (p<0.005), South-East Asians (p<0.005) and Chinese (p<0.005). When immunoglobulins were examined using sex, the significant findings were for IgG and IgM levels in HCV (IgG 16.1g/L males, vs. 17.6g/L females (p=0.003) and IgM 1.53g/L males vs. 1.81g/L females (p=0.006)). In HBV IgA levels (2.31g/L female vs. 2.68g/ L male (p=0.002) and IgM 1.23g/L female vs. 1.07g/L male (p=0.039) were found to be significant. NOSA status examined in 117 patients (17.2%) were found to be significantly positive for HCV vs HBV (19.9% vs 13% - p<0.05). Conclusion: This study shows that patients are significantly more likely to have abnormal IgG and M levels with HCV than HBV and there is also an ethnic and age difference. It is unclear whether these differences are due to a cause (immunoglobulins are fibrogenic) or an effect (fibrosis is immunogenic).
S1280 Ethnicity, Alcohol Consumption, and Cigarette use as Predictors for Hepatocellular Carcinoma: A Prospective Study Nghi B. Ha, Nghiem B. Ha, Aijaz Ahmed, Walid Ayoub, Tami Daugherty, Glen A. Lutchman, Gabriel Garcia, Allen D. Cooper, Peter B. Gregory, Emmet B. Keeffe, Mindie H. Nguyen PURPOSE: Data on alcohol and/or cigarette use as risk factors for hepatocellular carcinoma (HCC) has been conflicting and inconclusive. In the case of alcohol, it is not clear whether the effect is due to alcohol itself or alcohol-related cirrhosis. Thus, we proposed a study to examine alcohol use and cigarette use as risk factors associated with HCC in a large casecontrol study with a prospective questionnaire. METHODS: We conducted a case-control study of 984 patients: 253 HCC cases and 731 controls without HCC enrolled by convenience sampling between February 2001 and October 2009 at a university liver clinic in California. The ethnic make-up of the total study population was as follows: 42% Whites, 14% Hispanics, 3% African-Americans, 39% Asian Americans and 2% Others. Risk factors were examined through medical records and a prospective 12-page risk factor questionnaire administered by a research coordinator. All patients gave written informed consent. Alcohol use was calculated by cumulative grams of alcohol consumed up to the time of this study. Tobacco use was calculated by cumulative pack(s) of cigarette consumed up to the time of this study. Risk factors were evaluated using multivariate logistic regression. RESULTS: Cases were older (60±11 vs. 52±11, p<0.0001), more likely to be male (81% vs. 61.2%, p<0.0001), and more likely to have cirrhosis (85.6% vs. 73.6%, p<0.0001). Patients with cirrhosis consumed a significantly greater average amount of alcohol in total grams (log10) (5.6 vs. 4.9, p<0.00001) and used a significantly greater average amount of tobacco in cumulative packs (917 vs. 333, p=0.004). Cases had significantly greater lifetime tobacco use (1,202 vs. 635 packs, p=0.006). There were no significant differences in proportions of patients with family history of HCC or exposure to vinyl chloride among cases and controls. In multivariate logistic regression also inclusive of CPT score, etiologies of primary liver disease, and alcohol, significant independent predictors for HCC included age over 40 (OR=6.3, p= 0.001), male sex (OR=2.6, p<0.0001), presence of cirrhosis (OR=3.7, p<0.001), cumulative tobacco use > 1000 packs (OR=1.9, p=0.02), and Asian ethnicity compared to Whites and
S1278 Use of Ultrasound as the Initial Imaging Exam for Hepatocellular Carcinoma in High Risk Populations Jason B. Welch, Richa Shukla, Nnenna L. Igbo, Ashwani K. Singal, Joao F. Kazan-Tannus, Roger D. Soloway Background and Aims: Detection of Hepatocellular Carcinoma (HCC) in high risk populations has traditionally involved the use of ultrasound (US), followed by computed tomography (CT) or Magnetic Resonance Imaging (MRI) for confirmation of suspected lesions. No studies to date have specifically compared the accuracy of US in detecting HCC with that of CT or MRI. The aim of our study was to determine, retrospectively, in an unselected population of patients with cirrhosis, if an initial US could be as accurate as a subsequent CT or MRI in detecting HCC. Methods: We conducted a search of cases in which screening was performed with US and followed by CT or MRI within 6 months. Any patient with known HCC prior to a screening US was excluded. 1600 consecutive patients from 2004-2007 who had an initial US were reviewed, of which 160 fulfilled this sequence. This group included 34 cases of suspected HCC. Results: Of these 34 patients, 26 were correctly identified as having HCC by abdominal US, representing a sensitivity of 76.5%. The specificity for US in the detection of HCC was found to be 99.2% (1 false positive). In 8 cases where
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Hispanics (OR=2.9, p<0.0001). CONCLUSIONS: Cumulative tobacco use of > 1000 packs was an independent predictor for HCC but not alcohol consumption. Other significant independent predictors for HCC were Asian ethnicity, age over 40, male sex, and cirrhosis. Patients with risk factors for HCC should be strongly advised against tobacco use.
men and 13 women, 24 rectal cancer and 17 colon cancer, 61.4 years old) who underwent liver resection from September 2001 to January 2008. All patients underwent complete resection of the primary carcinoma with lymph nodes dissection. Radio frequency ablation therapy was performed by use of cool tip 2 cm or 3 cm. The duration of ablation was 6 minutes each time. Patient survival calculated by Kaplan-Meier method, complication, complication and hopital stay were compared between each group. [Results] The average diameter and number of liver metastasis was 2.8 cm, 2.5 in RF group and 3.8 cm, 1.5 in liver resection group (no significant difference). There was no significant difference about the number of therapy (1.53 (RF group) vs. 1.08 (liver resection group)). We found significantly shorter hospital stay among RF group patients than that among liver resection group (7.5 vs 27.9 days). The average follow-up time was 2.9 years in RF group and 2.8 years in liver resection group. No significant difference was found about 6 years patient survival between two groups (31.7 % in RF group vs. 31.1 % in liver resection group). There were one complication (5.6 %) in RF group (subserosal hematoma) and 4 (9.8 %) in liver resection group (2 bile leakage, one intestinal obstruction, one wound infection). No additional surgery was necessary for those patients with complication. There was no difference about the contents of chemotherapy after the treatment for liver metastasis between both of groups. [Discussion] Radio frequency ablation therapy can be safely performed and is effective treatment for liver metastasis from colorectal carcinoma.
S1281 Evaluation of the Effects of Molecular Target Agents by Tumor Marker Doubling Time Kenichiro Enooku, Ryosuke Tateishi, Fumihiko Kanai, Haruhiko Yoshida, Koji Uchino, Toru Arano, Eriko Goto, Ryota Masuzaki, Noriyo Yamashiki, Tadashi Goto, Shuichiro Shiina, Masao Omata, Kazuhiko Koike BACKGROUND/AIMS For the evaluation of response to cytostatic agents, determination of changes in tumor growth speed seems to be essential. RECIST, which lacks the dimension of time, may not be particularly suitable for these agents. The aim of this study is to elucidate the usefulness of tumor marker doubling time (DT) in the evaluation of response to a molecular target agent. PATIENTS AND METHODS A total of 25 patients with advanced HCC participated in the phase I/II clinical trial of TSU-68, a novel tyrosine kinase inhibitor of VEGF. We enrolled 15 patients whose alpha-fetoprotein (AFP) or des-gamma-carboxyprothrombin (DCP) showed exponential increase during wash-out phase before TSU administration. We analyzed the relationship between tumor marker DT and tumor volume DT measured on two CT examinations before the commencement of TSU-68 administration. Next, tumor marker DT in the first 8 weeks of TSU-68 administration was similarly calculated, and compared with DT before TSU-68 administration. DT should be elongated, or turn negative, if TSU-68 was effective. The evaluation based on tumor marker DT was compared with RECIST. Lastly, tumor marker DT after the cessation of TSU-68 was calculated and compared with DT in 4 weeks immediately before the cessation. RESULTS DT of tumor marker level and that of tumor volume before TSU-68 administration were almost identical (R2=0.94, P<0.001). The evaluation based on tumor marker DT comparison between before and during TSU-68 administration and that based on RECIST were compatible in most cases (12/15); discordance was observed in 3 cases judged as disease progression by RECIST due to substantial tumor necrosis without volume shrinkage or appearance of new lesions in spite of apparent effects on target lesions. In these cases DT elongation was observed, which suggested cytostatic effect of TSU-68. Tumor marker DT after the cessation of TSU86 administration was evaluated in 4 cases, where DT was shortened after the cessation. CONCLUSION Serum tumor marker levels can be used to evaluate viable tumor burden irrespective of the presence of tumor necrosis, which may compromise radiographic evaluation. This may be applicable to the evaluation of response to chemotherapy with cytostatic agents in particular.
S1284 Predictive Value of FDG PET-CT for Early Recurrence in Surgical Resection Against Hepatocellular Carcinoma Atsushi Hiraoka, Kojiro Michitaka, Masao Miyagawa, Hideki Kawasaki, Satoshi Hidaka, Takahide Uehara, Aki Hasebe, Yasunao Miyamoto, Tomoyuki Ninomiya, Hironori Ochi, Masashi Hirooka, Yoshimasa Yamashita, Norio Horiike, Yoichi Hiasa, Bunzo Matsuura, Morikazu Onji Background/Aim: The clinical efficacy of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) Positron Emission Tomography (PET) computed tomography (CT) for hepatocellular carcinoma (HCC) has not been established. Hepatic resection for HCC has been performed widely in Japan due to lack of donor for liver transplantation. Early recurrence of HCC has been known as a poor prognostic factor for death. Herein, we associated the predictive value of PET-CT for early recurrence in hepatic resection. Methods: From April 2006 to October 2009, 53 patients with naïve HCC who were examined by PET-CT before hepatic resection were enrolled. Accumulations of FDG [standardized uptake value (SUVmax)] in HCC and in liver, and the ratio of SUVmax (HCC/liver) (R-SUV) were calculated. Patients were divided into high R-SUV (1.5≤, H-group, n=19) and low R-SUV (1.5>, L-group, n=34). We evaluated prognostic factors for early recurrence after resection. Results: One was tumor node metastasis (TNM) stage I, 35 were II, 14 were III, and 3 were IV. Though, the frequencies with the high levels of protein induced by vitamin K absence or antagonist II (PIVKA-II: 200mAU/ ml<) and fucosylated alfa-fetoprotein (AFP) (AFP-L3: 15%<) were larger in H-group (52.9 vs 21.1%, 38.2 vs 10.5%, P<0.01), whereas there were no significant differences in the frequencies with high levels of AFP (100ng/ml<) and with large tumor diameter (5cm<), Child-Pugh class, the number of tumor, and TNM stage between both groups. The recurrentfree rate of L-group were higher than H-group (1- and 2-year recurrent-free rate: 100 and 67% vs 67 and 17%, respectively, P<0.01). PIVKA-II (200mAU/ml<), AFP-L3 (15%<), and total bilirubin (2mg/dl), and the high R-SUV (1.5≤) were the risk factors for early recurrence in univariate analysis (P<0.05, respectively). In multivariate analysis, high R-SUV (1.5≤) was the only risk factor (P<0.05). In pathological analysis, all were typical HCC. HCC nodules with Edmondson III showed higher R-SUV (3.0±1.8) than those with I and II (1.4±0.3 and 1.9±0.9) (P<0.01). Nodules with micro vascular invasion (vp) (+), micro intrahepatic metastasis (im) (+), and the nonboundary type nodules (single nodular type with extranodular growth, confluent multinodular or invasive type) showed higher R-SUV than those with vp (-), im (-), or the boundary type (vaguely nodular or single nodular type) (3.6±2.4 vs 2.0±0.9, 3.5±2.3 vs 1.9±0.8, 2.9±1.8 vs 1.6±0.5, respectively, P<0.01). Conclusion: HCC with high R-SUV (1.5≤) related to early recurrence of HCC after resection. RSUV had relation to pathological findings. R-SUV was found to be a useful prediction marker for the early recurrence of HCC after resection.
S1282 Rate of Stage Transition From Early to Advanced Hepatocellular Carcinoma Toru Arano, Ryosuke Tateishi, Shuichiro Shiina, Koji Uchino, Keniciro Enooku, Eriko Goto, Ryota Masuzaki, Hayato Nakagawa, Yuji Kondo, Noriyo Yamashiki, Tadashi Goto, Hajime Fujie, Masao Omata, Haruhiko Yoshida, Kazuhiko Koike Background and Aims: In spite of advances in diagnosis and treatment of hepatocellular carcinoma (HCC), recurrence of HCC is very frequent even after curative treatments, resulting in uncontrollable cancer or hepatic failure, and long-term prognosis of HCC remains poor. We analyzed progression rates from early stage HCC to terminal stage and death, and simulated expected effects of intervention in each stage. Methods: Among 666 patients with HCC who received radiofrequency ablation at the authors' hospital between 1999 and 2004, 359 patients who presented HCC not more than 3 in number and not larger than 3 cm in diameter were enrolled. Clinical stages after initial treatment were divided into A (n ≦ 3 and size ≦ 3 cm), B (n > 3 or size > 3cm), C (with extrahepatic metastasis or vascular invasion) according to BCLC staging classification. The progression rates between stages were calculated by using competing event model, and temporal transition between stages was simulated based on a Markov chain model. Results: Enrolled patients consists of 232 males and 127 females (mean ± SD age, 68 ± 8.1 years; mean tumor size, 2.1 ± 0.5 cm; mean tumor number, 1.5 ± 0.7; Child A/B, 246/111; HCV/HBV, 290/31). By fitting an exponential model to the results of competing event analysis, the annual rate of stage transition from A to B, A to C and A to death were calculated as 6.3, 1.3% and 3.5%, respectively. Among those who advanced to stage B, the annual rates of transition to stage C and death were 16.1% and 14.2%, respectively. The annual rate of transition from C to death was 72%. When the analysis was performed with respect to liver function (Child A vs. B/C), significant difference was observed in the rates of transition from A to death (2.4% vs. 7.5%). By fitting Markov chain model, 3- and 5-year survival rates of Child A vs. B/C patients were estimated as 88.4% and 76.4% vs. 75.7% and 59.1%, respectively. When compared to actual data (89.1% and 71.4% for Child A and 71.7% and 51.8% for Child B/C), the survival rates were slightly overestimated at 5 years. The effects of a treatment that prolongs the duration of stage A, B and C by 1.5 times were estimated as increase in 5-year survival rates of 2.6%, 0.8% and 1.5%, respectively. Conclusion: To divide the complicated clinical course of HCC into several stages, we can evaluate the effects of treatments such as recurrence suppression, adjuvant therapy or molecular targeting therapy on the overall survival independently.
S1285 Type 2 Diabetes Mellitus is Associated With Hepatic Fibrosis in Chronic Hepatitis C Patients in Taiwan Chia-Yen Dai, Jee-Fu Huang, Ming-Yen Hsieh, Nai-Jen Hou, Zu-Yau Lin, Shinn-Cherng Chen, Liang-Yen Wang, Wan-Long Chuang, Ming-Lung Yu Background and aims: Type 2 diabetes mellitus (DM) is one of the extrahepatic manifestations of hepatitis C virus (HCV) infection. The aims of the study were to elucidate the association between DM and severity of fibrosis and the associations between these parameters and the virological characteristics in CHC patients in Taiwan. Methods: A large scale study enrolling CHC patients with biopsy-proven chronic hepatitis was conducted. Serum HCV RNA, HCV RNA levels and HCV genotypes 1a, 1b, 2a, 2b and 3a were determined. The liver histology was assessed using the modified histologic activity index (HAI) scoring system and steatosis was quantified as the percentage of hepatocytes that contained fat droplets. Results: We enrolled 927 CHC patients (547 males, mean age: 51.0 years, 506 with type 1 infection) with 37.8% and 27.6% patients having hepatic steatosis and severe fibrosis (F3-4), respectively. DM was diagnosed in 19.2% patients. Multivariate logistic regression analyses showed that male gender, a higher ALT level, the presence of steatosis, severe fibrosis (F3-4) and a higher BMI were independent factors associated with DM. Variables independently associated with steatosis were presence of DM, a higher necroinflammatory score, and a higher BMIin CHC patients. Presence of DM, a higher necroinflammatory score, and a higher BMI were independent factors associated with severe fibrosis in CHC patients. The virologic characteristics including HCV genotype and HCV RNA levels were not associated with DM, severe fibrosis and steatosis in CHC patients. Conclusion: we found in the large scale study that DM was associated with histological characteristics of steatosis and severe fibrosis. DM, BMI and necroinflammation activity are factors commonly associated both steatosis and severe
S1283 Effect of Radio Frequency Ablation Therapy for Liver Metastasis From Colorectal Cancer Masaru Hirata [Background] We compared the complication and patient survival between radio frequency ablation therapy and liver resection for liver metastasis from colorectal cancer. [Patients and Method] Patients consisted of 18 cases (12 men and 6 women, 9 rectal cancer and 9 colon cancer, 63.1 years old) who underwent radio frequency ablation therapy and 41 cases (28
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