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M2072 Secondary Gallbladder Tumors - a Korean Experience
liver transplantation. However, overall tumor size was not significantly altered during TACE therapy and significant overall survival benefit could not be detected depending on the tumor size. Conclusions: Our data show that TACE therapy prior to liver transplantation does not offer a significant advantage towards overall survival. Significant survival benefit could be observed if LTX was performed within 3 months - regardless whether patients had a prior TACE therapy or not. M2072 Secondary Gallbladder Tumors - a Korean Experience Won Jae Yoon, Youn Joo Kim, Ji Kon Ryu, Yong-Tae Kim, Yong Bum Yoon Background/Aims: Secondary gallbladder tumors (SGBTs) are rare. Although melanoma and renal cell carcinoma are reported to metastasize to the gallbladder (GB), the data are from autopsy series of these tumors. There is little data on secondary involvement of GB by other tumors. Also, the proportion of SGBTs among GB malignancies is not well known. The aims of this study were to evaluate the characteristics of and the proportion of SGBTs among GB malignancies. Methods: We collected all pathologically diagnosed GB malignancies from the database of Seoul National University Hospital from 1999 to 2007. We evaluated the clinicopathological characteristics of the patients with SGBTs. Survival analyses were performed using the Kaplan-Meier method. Factors associated with prolonged survival were determined using the log-rank test. For factors of age at primary tumor diagnosis, age at diagnosis of the SGBT, sex, and those associated with prolonged survival in univariate analysis at P<0.20 were included as covariates in the Cox regression. Two-sided P values of <0.05 were considered statistically significant. Result: Of 417 cases of GB malignancies, 49 (37 male) were SGBTs, accounting for 11.8% of GB malignancies. The median age at diagnosis of the primary malignancy was 59 years. Primary malignancies originated from extrahepatic bile duct (n=16), stomach (n=10), liver (n=10), colorectum (n=6), kidney (n=2), skin (n=2), uterine cervix (n=1), appendix (n=1), and pancreas (n=1). Secondary involvement of the GB was anticipated in 22 (44.9%) patients. The GB was involved by direct invasion in 29 cases and by metastasis in 20. Thirty-three cases were diagnosed synchronously. Sixteen cases were diagnosed metachronously, presenting with cholecystitis (n=4), abdominal pain (n=3), jaundice (n=1), weight loss (n=1), and elevation of serum CA 19-9 (n=1); 8 patients were asymptomatic. Median survival after diagnosis of SGBT was 11.6 months. On multivariate analysis, complete resection of all tumor present was the only factor associated with prolonged survival (hazards ratio, 0.27; 95% confidence interval, 0.09-0.82; P=0.022); presentation with cholecystitis was associated with worsened survival (hazards ratio, 8.43; 95% confidence interval 1.85 - 38.32; P=0.006). Conclusion: SGBTs accounted for 11.8% of all pathologically diagnosed GB malignancies. Extrahepatic bile duct, liver, and stomach cancers were the three most common cancers with had secondary GB involvement. Median survival after diagnosis of SGBT was 11.6 months. Complete resection of all tumor present was associated with prolonged survival. Presentation with cholecystitis was associated with worsened survival.
M2070 Significant Survival Benefit from Transarterial Chemoembolization As Palliative Therapy for Hepatocellular Carcinoma Tobias Meister, Hauke Heinzow, Dominik Nass, Michael Köhler, Hansjörg Ullerich, Wolfram W. Domschke, Dirk Domagk Background: Hepatocellular Carcinoma (HCC) is the most common liver tumor in patients with liver cirrhosis. The outcome of untreated patients with HCC is poor with a median survival rate of only 8 to 10 months. In advanced stage tumors Transarterial Chemoembolisation (TACE) is a possible and well established therapeutic option. Patients und Methods: In the present study we retrospectively analyzed 42 patients with histologically proven HCC who underwent TACE as a palliative therapy (mean age 75 years) in the years 2000-2008. The chemotherapeutic agent used for TACE was doxorubicine/cisplatin/lipiodol. Primary endpoint was the overall survival from the time of diagnosis of HCC until the survival status at the valuation date of March 1st, 2008. SPSS 16.0 for Windows was used for statistical analysis. Statistical analysis was performed with the chi square test.The Kaplan Meier method was used to calculate survival, and subgroups of interest were compared with the log Rank test for statistical significance. Results: The median survival of patients who had undergone TACE as a palliative therapy was 17 months. The Okuda stage was the following: stage I 25%, stage II 65%, stage III 10%. Overall survival clearly depended on the initial Okuda stage with longest survival seen in Okuda stage I (median survival Okuda I: 46 months, Okuda stage II: 12 months, p < 0.05). Patients with tumor regression under TACE had a significant longer overall survival compared to patients with stable disease or tumor progression (tumor regression/stable disease/tumor progression: 60/18/17 months, respectively, p< 0.01). Conclusions: Patients who received TACE as a palliative therapy the overall median survival time with 17 months was clearly longer compared to published data of untreated patients in Europe and Japan. Significant survival benefit was also seen in early tumor stage and tumor response to TACE with 4 - 6fold longer median survival.
M2073 Excretory-Secretory Products of Clonorchis Sinensis Induce Cholangiocyte Apoptosis and Proinflammatory Cytokine Production Won Il Park, Ung Suk Yang, Geun Am Song, Jae Hun Cheong, Ji Won Kim, Hyung Wook Kim Clonorchis sinensis is a trematode parasite in human liver and one of the common causes of parasitic infestations in East Asia. In this regions, clonorchiasis is considered as an important cause of recurrent pyogenic cholangitis and cholangiocarcinoma. But the exact mechanism was not clearly elucidated. To clarify the effects of excretory-secretory products of C. sinensis on bile duct epithelial cells, we investigated their effects on the dog gallbladder epithelial cell line(DBDE). The excretory-secretory products of C. sinensis altered the proportion of cells in each stage of the cell cycle and induced DBDE cell proliferation. Among cell cycle-related proteins, the expression of p21 cell cycle inhibitor and p53 tumor suppressor protein decreased markedly after treatment with excretory-secretory products. In addition, the activity of the phospholipase D(PLD) was up-regulated. Chemical inhibitor of PLD activation was used to demonstrate that the PLD is a key factor in the control of cell proliferation in DBDE cells. The present results also demonstrate that excretory-secretory products of C. sinensis stimulate H2O2-derived apoptosis and increase the production of the proinflammatory cytokine TNF-α. We suggest that the excretory-secretory products released from C. sinensis during infestation may play an important role in the development of cholangiocarcinoma via the overgrowth of the bile duct epithelium.
Figure 1: Palliative TACE therapy of patients with Okuda Stage I vs. Okuda Stage II M2071 Transarterial Chemoembolization (TACE) As a Bridging Therapy Prior to Liver Transplantation (LTX) in Patients with Hepatocellular Carcinoma (HCC): Do Patients Benefit ? Tobias Meister, Hauke Heinzow, Dominik Nass, Michael Köhler, Hansjörg Ullerich, Wolfram W. Domschke, Dirk Domagk
M2074
Background: The outcome of untreated patients with HCC is poor with a median survival rate of only 8 to 10 months. TACE is a well established method for treating patients with HCC as a bridging concept prior to LTX. Patients und Methods: We retrospectively analyzed 52 patients with proven HCC. 26 patients had TACE as a bridging therapy (mean age 60 years) and 26 patients had LTX without prior TACE therapy. The chemotherapeutic agent used for TACE was doxorubicine/cisplatin/lipiodol. Primary endpoint was the overall survival until death. The Kaplan Meier method was used to calculate survival, and subgroups of interest were compared with the log Rank test for statistical significance. Results: TACE as briding therapy vs. LTX only: There was no significant difference in terms of age, CHILD classification or underlying disease. The initial Okuda stage revealed no statistical relevant survival benefit for one of the two groups. The disease free survival after LTX was highly significant prolonged if LTX was performed within 3 months after diagnosis of HCC (> 75 vs 29 months, p= 0.021). Fulfillment of the Milan criteria had influence of the disease free survival: In the non-TACE group there was a tendency towards longer disease free survival for patients who fulfilled the Milan criteria (> 72 vs 33 months, p= 0.08). This effect could not be seen in the TACE group (p= 0.54). The majority of patients had stable disease until
[Objective] Advanced gallbladder cancer still remains as tumors with poor prognosis. We analyzed clinicopathological features of patients with advanced gallbladder cancer for establishment of optimal strategy of treatment. [Materials and methods] Medical charts of 41 patients (male 14, female 27; median age 64.2 year) with advanced gallbladder cancer (UICC pT2-4) who underwent curative resection were retrospectively reviewed. Surgical procedures included extended cholecystectomy with or without resection of the extrahepatic bile duct in 13, segmental or major hepatic resection in 6, resection of segmental or major hepatic lobe and extrahepatic bile duct in 14, pancreatoduodenectomy in 5, and pancreatoduodenectomy with segmental hepatic resection in 3. P value <0.05 were considered as significant. [Results] With a median follow-up of 25 months, overall survival rate at 1-, 3-, and 5-year was 80.0%, 49.7%, and 41.4% respectively. Survival rates at 5-year in patients with UICC pT2, pT3, and pT4 were 56.3%, 38.8%, and 20.0% respectively. Significant differences were found between pN0 and pN1 group whose survival rate at 1-, 3-, and 5-year were
Lymph Node Metastasis Is An Important Factor for Long-Term Survival of Patients with Gallbladder Cancer Who Underwent Curative Surgery Shunji Narumi, Kenichi Hakamada, Yoshikazu Toyoki, Keinosuke Ishido
A-479
AGA Abstracts
AGA Abstracts
(AFP) (>100 ng/ml), AFP-L3 (>15%) and des-γ carboxyprothrombin (DCP) (>60 AU/ml) was seen in 12, 10, and 25 patients respectively. The modalities of diagnosis of bone metastasis were computer tomography (CT) (16 cases), magnetic resonance imaging (MRI) (10), bone scintigram (5), operation (1) and positron emission tomography (PET)-CT (1). The sites of bone metastasis were vertebra (17 cases), rib (12), pelvis (10), cranial bone (4), femur (4), sternum (3), and others (2). The average (SD) duration from the diagnosis of HCC to bone metastasis was 713 (±570) days. During the study period, 30 (91%) patients died (mean(SD) 355(±93) days from the diagnosis of bone metastasis). There was no significant difference in age, gender, stage, platelet count and serum tumor marker levels except for AFP between the two groups. Factors indicating a significant difference were serum AFP level, Child-Pugh classification and control of intrahepatic HCC by univariate analysis (p<0.05). However, control of intrahepatic HCC lesions was a single significant factor showing a significant difference between the two groups by multivariate analysis. The 1-year survival rate after diagnosis with and without control of intrahepatic HCC was 77% and 9%, respectively (p <0.0001, Log-rank test ). CONCLUSION:Control of intrahepatic lesions is a vital factor in the survival of HCC patients with bone metastasis.
M2070 Significant Survival Benefit from Transarterial Chemoembolization As Palliative Therapy for Hepatocellular Carcinoma Tobias Meister, Hauke Heinzow, Dominik Nass, Michael Köhler, Hansjörg Ullerich, Wolfram W. Domschke, Dirk Domagk Background: Hepatocellular Carcinoma (HCC) is the most common liver tumor in patients with liver cirrhosis. The outcome of untreated patients with HCC is poor with a median survival rate of only 8 to 10 months. In advanced stage tumors Transarterial Chemoembolisation (TACE) is a possible and well established therapeutic option. Patients und Methods: In the present study we retrospectively analyzed 42 patients with histologically proven HCC who underwent TACE as a palliative therapy (mean age 75 years) in the years 2000-2008. The chemotherapeutic agent used for TACE was doxorubicine/cisplatin/lipiodol. Primary endpoint was the overall survival from the time of diagnosis of HCC until the survival status at the valuation date of March 1st, 2008. SPSS 16.0 for Windows was used for statistical analysis. Statistical analysis was performed with the chi square test.The Kaplan Meier method was used to calculate survival, and subgroups of interest were compared with the log Rank test for statistical significance. Results: The median survival of patients who had undergone TACE as a palliative therapy was 17 months. The Okuda stage was the following: stage I 25%, stage II 65%, stage III 10%. Overall survival clearly depended on the initial Okuda stage with longest survival seen in Okuda stage I (median survival Okuda I: 46 months, Okuda stage II: 12 months, p < 0.05). Patients with tumor regression under TACE had a significant longer overall survival compared to patients with stable disease or tumor progression (tumor regression/stable disease/tumor progression: 60/18/17 months, respectively, p< 0.01). Conclusions: Patients who received TACE as a palliative therapy the overall median survival time with 17 months was clearly longer compared to published data of untreated patients in Europe and Japan. Significant survival benefit was also seen in early tumor stage and tumor response to TACE with 4 - 6fold longer median survival.
M2073 Excretory-Secretory Products of Clonorchis Sinensis Induce Cholangiocyte Apoptosis and Proinflammatory Cytokine Production Won Il Park, Ung Suk Yang, Geun Am Song, Jae Hun Cheong, Ji Won Kim, Hyung Wook Kim Clonorchis sinensis is a trematode parasite in human liver and one of the common causes of parasitic infestations in East Asia. In this regions, clonorchiasis is considered as an important cause of recurrent pyogenic cholangitis and cholangiocarcinoma. But the exact mechanism was not clearly elucidated. To clarify the effects of excretory-secretory products of C. sinensis on bile duct epithelial cells, we investigated their effects on the dog gallbladder epithelial cell line(DBDE). The excretory-secretory products of C. sinensis altered the proportion of cells in each stage of the cell cycle and induced DBDE cell proliferation. Among cell cycle-related proteins, the expression of p21 cell cycle inhibitor and p53 tumor suppressor protein decreased markedly after treatment with excretory-secretory products. In addition, the activity of the phospholipase D(PLD) was up-regulated. Chemical inhibitor of PLD activation was used to demonstrate that the PLD is a key factor in the control of cell proliferation in DBDE cells. The present results also demonstrate that excretory-secretory products of C. sinensis stimulate H2O2-derived apoptosis and increase the production of the proinflammatory cytokine TNF-α. We suggest that the excretory-secretory products released from C. sinensis during infestation may play an important role in the development of cholangiocarcinoma via the overgrowth of the bile duct epithelium.
Figure 1: Palliative TACE therapy of patients with Okuda Stage I vs. Okuda Stage II M2071 Transarterial Chemoembolization (TACE) As a Bridging Therapy Prior to Liver Transplantation (LTX) in Patients with Hepatocellular Carcinoma (HCC): Do Patients Benefit ? Tobias Meister, Hauke Heinzow, Dominik Nass, Michael Köhler, Hansjörg Ullerich, Wolfram W. Domschke, Dirk Domagk
M2074
Background: The outcome of untreated patients with HCC is poor with a median survival rate of only 8 to 10 months. TACE is a well established method for treating patients with HCC as a bridging concept prior to LTX. Patients und Methods: We retrospectively analyzed 52 patients with proven HCC. 26 patients had TACE as a bridging therapy (mean age 60 years) and 26 patients had LTX without prior TACE therapy. The chemotherapeutic agent used for TACE was doxorubicine/cisplatin/lipiodol. Primary endpoint was the overall survival until death. The Kaplan Meier method was used to calculate survival, and subgroups of interest were compared with the log Rank test for statistical significance. Results: TACE as briding therapy vs. LTX only: There was no significant difference in terms of age, CHILD classification or underlying disease. The initial Okuda stage revealed no statistical relevant survival benefit for one of the two groups. The disease free survival after LTX was highly significant prolonged if LTX was performed within 3 months after diagnosis of HCC (> 75 vs 29 months, p= 0.021). Fulfillment of the Milan criteria had influence of the disease free survival: In the non-TACE group there was a tendency towards longer disease free survival for patients who fulfilled the Milan criteria (> 72 vs 33 months, p= 0.08). This effect could not be seen in the TACE group (p= 0.54). The majority of patients had stable disease until
[Objective] Advanced gallbladder cancer still remains as tumors with poor prognosis. We analyzed clinicopathological features of patients with advanced gallbladder cancer for establishment of optimal strategy of treatment. [Materials and methods] Medical charts of 41 patients (male 14, female 27; median age 64.2 year) with advanced gallbladder cancer (UICC pT2-4) who underwent curative resection were retrospectively reviewed. Surgical procedures included extended cholecystectomy with or without resection of the extrahepatic bile duct in 13, segmental or major hepatic resection in 6, resection of segmental or major hepatic lobe and extrahepatic bile duct in 14, pancreatoduodenectomy in 5, and pancreatoduodenectomy with segmental hepatic resection in 3. P value <0.05 were considered as significant. [Results] With a median follow-up of 25 months, overall survival rate at 1-, 3-, and 5-year was 80.0%, 49.7%, and 41.4% respectively. Survival rates at 5-year in patients with UICC pT2, pT3, and pT4 were 56.3%, 38.8%, and 20.0% respectively. Significant differences were found between pN0 and pN1 group whose survival rate at 1-, 3-, and 5-year were
Lymph Node Metastasis Is An Important Factor for Long-Term Survival of Patients with Gallbladder Cancer Who Underwent Curative Surgery Shunji Narumi, Kenichi Hakamada, Yoshikazu Toyoki, Keinosuke Ishido
A-479
AGA Abstracts
AGA Abstracts
(AFP) (>100 ng/ml), AFP-L3 (>15%) and des-γ carboxyprothrombin (DCP) (>60 AU/ml) was seen in 12, 10, and 25 patients respectively. The modalities of diagnosis of bone metastasis were computer tomography (CT) (16 cases), magnetic resonance imaging (MRI) (10), bone scintigram (5), operation (1) and positron emission tomography (PET)-CT (1). The sites of bone metastasis were vertebra (17 cases), rib (12), pelvis (10), cranial bone (4), femur (4), sternum (3), and others (2). The average (SD) duration from the diagnosis of HCC to bone metastasis was 713 (±570) days. During the study period, 30 (91%) patients died (mean(SD) 355(±93) days from the diagnosis of bone metastasis). There was no significant difference in age, gender, stage, platelet count and serum tumor marker levels except for AFP between the two groups. Factors indicating a significant difference were serum AFP level, Child-Pugh classification and control of intrahepatic HCC by univariate analysis (p<0.05). However, control of intrahepatic HCC lesions was a single significant factor showing a significant difference between the two groups by multivariate analysis. The 1-year survival rate after diagnosis with and without control of intrahepatic HCC was 77% and 9%, respectively (p <0.0001, Log-rank test ). CONCLUSION:Control of intrahepatic lesions is a vital factor in the survival of HCC patients with bone metastasis.