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Oral adyuvant treatment for colorectal cancer
A1396 AGA ABSTRACTS
GASTROENTEROLOGY Vol. 118, No.4
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THE SAFETY AND EFFICACY OF PERITONEOVENOUS SHUNT FOR PALLIATION OF MALIGNANT ASCITES. Yan Lau, James R. Kirkpatrick, Donald R. Duerksen, Univ of Manitoba, Winnipeg, MB, Canada. Ascites is a common complication of advanced malignancies metastatic to the peritoneal cavity. Medical therapy with diuretics and paracentesis often fails to palliate patients with gastrointestinal and respiratory symptoms. The specific aim of this study is to determine if a Denver peritoneovenous shunt (PVS) is safe and effective in the palliation of patients with malignant ascites. Methods: A retrospective review of patients with malignant ascites who had a PVS between 1980 and 1999 was performed. A single surgeon at a single institution performed all shunts. Age, sex, weight, and Kamofsky performance scores were retrieved. Coagulation profile and liver and renal function were obtained. Postoperative complications of coagulopathy, shunt occlusion, infection, gastrointestinal bleeding, and encephalopathy were recorded. Results: 67 patients with PVS were identified. Malignancies included 24 ovarian, 21 gastrointestinal tract, 10 breast, 4 lung, and 8 other cancers. There was a female predominance (76%). Mean age was 61.1 :!: 11.3 years. Mean days of hospitalization were 23.1 :!: 21.4 days and mean follow up was 100.7 :!: 174.5 days. 56% of patients had failed diuretics and repeated large volume paracentesis. Preoperatively, the average albumin was 28 gIL and alkaline phosphatase was 213 units/L. The mean weight decreased after shunt surgery by 5.8 kg (p
ORAL ADYUVANTTREATMENT FOR COLORECTAL CANCER. Diego Ledro-Cano, Diego Ledro-Molina, Jose Luis Brasero-Asencio, Juan Manuel HERRERIAS Jr, Juan Manuel Herrerias, a H V Macarena, Sevilla, Spain. Aims. We compared two chemotherapeutic treatment schedules after surgery in colon cancer. Also we compared those schedules together with radiotherapy after surgery in rectal cancer. We assessed toxicity, relapses, metastases, deaths, global survival, and disease-free survival. Subjects and Methods. 50 patients with colon cancer were enrolled in this study. There were 40 patients who suffered from rectal cancer. Follow-up: Two years since surgery. 25 patients with colon cancer received Tegafur 400 mg b.i.d p.o plus folinic acid 30 mg b.i.d p.o. Other 25 patients received Tegafur 400 mg b.i.d p.o plus levamisol 50 mg t.i.d every three day two weeks per month. Patients with Rectal cancer received those same schedules plus 50 Gy radiotherapy for one month. Results. In the colon cancer levamisol group show more deaths (16% versus 23%), less metastases (16% versus 24%) and same relapses (4%) than folinic acid group. In the rectal cancer, The levamisol group show less deaths (15% versus 30%), less relapses (15% versus 20%) and less metastases (10% versus 30%). In the Colon Cancer, the levamisol group show more toxicity grade according to WHO classification than folinic acid group (44% versus 32%), although never beyond grade 2, The gastrointestinal toxicity was greater in the levamisol group (32% versus 16%) and also the hematological toxicity was greater in this group (32% versus 24%). In Rectal cancer, toxicity was below grade 2. Gastrointestinal toxicity was greater in the levamisol group (15% versus 5%). Hematological toxicity was similar in both groups of rectal cancer (50%). In colon cancer, Global Survival was greater in the folinic group than in the levamisol group (88% versus 84%). On the other hand, in the rectal cancer, the global survival was greater in the levamisol group (88% versus 70%). Disease-free Survival was greater in the folinic acid group (72% versus 60%) in the colon cancer. In the rectal cancer, the disease-free survival was greater in the levamisol group (60% versus 40%). Conclusion: Oral treatment results in few side effects and low toxicity, improve quality of life of patients and make the survival. substantial.
6343 LOCALIZATION OF THIOREDOXIN REDUCTASE MRNA IN COLORECTAL CANCER TISSUE BY IN-SITU HYBRIDIZATION. Sandra Lechner, Wibke Ballhom, Ulf Mueller-Ladner, Christopher Benzing, Juergen Schoelmerich, Frauke Bataille, Josef Rueschoff, Frank Kullmann, Dept of Internal Medicine I, Univ of Regensburg, Regensburg, Germany; Dept of Pathology, Univ of Regensburg, Regensburg, Germany; Dept of Pathology, Kassel, Germany. Background: Thioredoxin (Trx) and thioredoxin reductase (TR) are redox proteins that have been implicated in cellular events like proliferation or apoptosis. Trx-mRNA has been reported to be upregulated in several human tumors. Thus, the TR-Trx system could play an important role in regulating cell growth and death. Therefore we analyzed the expression and location of TR in a series of colon cancer tissues by in situ hybridization. Methods: Quantitative RT-PCR was performed using gene specific primers for TR in order to quantify the amount of TR mRNA in different cell lines. TR RNA probes were labelled with digoxigenin-UTP. Hybridization was performed overnight at 50°C. To detect TR mRNA, an anti-digoxigenin antibody was applied. Experiments were performed using matched pairs of normal and colon cancer or adenoma tissue, and colon tissue from a patient with Crohn's disease. Results: The colon cancer cell lines HCT-15 and LoVo expressed much more TR-mRNA than HT-29 or SW480. Furthermore, 23132/87- (gastric cancer), A549- (lung cancer) and HT1080- (fibrosarcoma) cells expressed high levels of TR-mRNA, whereas BT20(breast cancer) and Caki 1- (kidney cancer) cells expressed neglectable amounts of TR-mRNA. All tissue sections (normal, inflammatory and neoplastic) showed a positive hybridization signal for TR-mRNA. Positive cells were found between, but not within the colon crypts. None of the epithelial cells were positive for the TR-probe, whereas more than 70% HT29 cells were positive. By immunhistochemistry we could show that the in situ positive cells were CD68 and CD45 negative, but some of them were CD3 positive. A high number of TR-positive cells were found in inflammatory infiltrates of Crohn's disease. Colon cancer tissues showed a frequent number of TR-RNA positive cells in non-neoplastic areas, but an reduced number of TR-positive cells in preneoplastic or neoplastic areas. Conclusions: In colon cancer tissue TR is expressed by lymphocytes (CD3 positive) and other cells e.g. granulocytes. In contrast to the cell culture experiments, colon epithelial cells (neoplastic or non-neoplastic) were not positive for TR-mRNA probe. It is quite possible that the loss of cell-cell interactions in cell culture leads to e.g. a stress induced upregulation of TR-mRNA. The decrease ofTR-positive cells between crypts in neoplastic areas is remarkable and implicates that the loss of TR might contribute to tumor promotion by reduced defense mechanisms. This research was funded by the DFG (Ku 1024/6-1, Mu 138311-1)
6345 MUCOUS PHENOTYPIC EXPRESSION OF GASTRIC ADENOCARCINOMA IN KOREA. Ok-Jae Lee. Woo-Song Ha, Hidenobu Watanabe, Gyeong-sang National Univ Coli of Medicine, Chinju, South Korea; Niigata Univ Sch of Medicine, Niigata, Japan. Background!Aim: Histochemical and immunohistochemical studies for mucin contained in tumor allowed the mucous phenotypic classification of gastric adenocarcinomas. We investigated the mucous phenotypic expression of Korean gastric adenocarcinomas and its relationships with clinical and histopathological characteristics. Methods: Histochemical and immunohistochemical stainings for paradoxical concanavalin A, MUC5AC, MUC-2 glycoprotein and CDIO were performed in 74 surgically obtained gastric adenocarcinomas. Results: Among 74 gastric adenocarcinomas, 30 (40.5%) expressed gastric phenotype(lO foveolar and 20 foveolo-glandular), 20 (27.0%) intestinal phenotype(7 complete and 13 incomplete), 15 (20.3%) mixed gastric-intestinal phenotype and 9 (12.2%) undetermined type. The gastric and gastric predominant types were 54.1% (40/74), and intestinal and intestinal predominant types 31.1% (23/74). No relationship between mucous phenotypic expression and tumor location was found. Among 21 papillary and tubular adenocarcinomas, 5 (23.8%) expressed predominantly gastric phenotype and 12 (57.1%) intestinal phenotype. Among 53 poorly differentiated adenocarcinomas, signet ring cell carcinomas and mucinous adenocarcinomas, 35 (66.0%) were gastric predominant and II (20.8%) were intestinal predominant phenotypes. 35 out of 40 (87.5%) gastric predominant cancers were poorly differenciated, signet ring cell or mucinous adenocarcinomas. Helicobacter pylori infection rates were 87.5%, 91.3%, and 66.7% in gastric predominant, intestinal predominant, and undetermined phenotypes, respectively. Conclusions: Korean gastric adenocarcinomas expressed predominantly gastric phenotype and there was no association between mucous phenotypic expression and tumor location. However, mucous phenotype may be associated with differentiation of gastric adenocarcinoma and Helicobacter pylori infection.
6346 UNCOUPLING PROTEIN-2 EXPRESSION IN HUMAN HEPATOCELLULAR CARCINOMA. Fung-Yee J. Lee, Paul Bs Lai, Alexender Lau, Siu-Man Ng, Ursula Pf Chan, Shali Shen, Wan-Yee Lau, Cuhk, Hong Kong, Hong Kong. Background: Previous studies have demonstrated that uncoupling protein-2 (UCP-2) gene expression can be induced by tumor necrosis factor (TNF) and lipids. As the level ofTNF secretion increased during the development of cirrhosis, UCP-2 gene expression is induced (unpublished data). In our locality, the majority of hepatocellular carcinoma (HCC) develop in hepatitis B-related cirrhosis, the expression of UCP-2 gene in human HCC is unknown. The aim of this study is to evaluate the expression of UCP-2 gene in human hepatocellualr carcinoma. Methods: Forty-six hepatitis B carriers with histologially confirmed HCC were included in the present study. Tissues collected from the resected liver specimen, including the tumor and the non-tumorous portions were snap-frozen in liquid nitrogen. Total RNA was extracted and semi-quantitative RT-PCR using the human
GASTROENTEROLOGY Vol. 118, No.4
6342
6344
THE SAFETY AND EFFICACY OF PERITONEOVENOUS SHUNT FOR PALLIATION OF MALIGNANT ASCITES. Yan Lau, James R. Kirkpatrick, Donald R. Duerksen, Univ of Manitoba, Winnipeg, MB, Canada. Ascites is a common complication of advanced malignancies metastatic to the peritoneal cavity. Medical therapy with diuretics and paracentesis often fails to palliate patients with gastrointestinal and respiratory symptoms. The specific aim of this study is to determine if a Denver peritoneovenous shunt (PVS) is safe and effective in the palliation of patients with malignant ascites. Methods: A retrospective review of patients with malignant ascites who had a PVS between 1980 and 1999 was performed. A single surgeon at a single institution performed all shunts. Age, sex, weight, and Kamofsky performance scores were retrieved. Coagulation profile and liver and renal function were obtained. Postoperative complications of coagulopathy, shunt occlusion, infection, gastrointestinal bleeding, and encephalopathy were recorded. Results: 67 patients with PVS were identified. Malignancies included 24 ovarian, 21 gastrointestinal tract, 10 breast, 4 lung, and 8 other cancers. There was a female predominance (76%). Mean age was 61.1 :!: 11.3 years. Mean days of hospitalization were 23.1 :!: 21.4 days and mean follow up was 100.7 :!: 174.5 days. 56% of patients had failed diuretics and repeated large volume paracentesis. Preoperatively, the average albumin was 28 gIL and alkaline phosphatase was 213 units/L. The mean weight decreased after shunt surgery by 5.8 kg (p
ORAL ADYUVANTTREATMENT FOR COLORECTAL CANCER. Diego Ledro-Cano, Diego Ledro-Molina, Jose Luis Brasero-Asencio, Juan Manuel HERRERIAS Jr, Juan Manuel Herrerias, a H V Macarena, Sevilla, Spain. Aims. We compared two chemotherapeutic treatment schedules after surgery in colon cancer. Also we compared those schedules together with radiotherapy after surgery in rectal cancer. We assessed toxicity, relapses, metastases, deaths, global survival, and disease-free survival. Subjects and Methods. 50 patients with colon cancer were enrolled in this study. There were 40 patients who suffered from rectal cancer. Follow-up: Two years since surgery. 25 patients with colon cancer received Tegafur 400 mg b.i.d p.o plus folinic acid 30 mg b.i.d p.o. Other 25 patients received Tegafur 400 mg b.i.d p.o plus levamisol 50 mg t.i.d every three day two weeks per month. Patients with Rectal cancer received those same schedules plus 50 Gy radiotherapy for one month. Results. In the colon cancer levamisol group show more deaths (16% versus 23%), less metastases (16% versus 24%) and same relapses (4%) than folinic acid group. In the rectal cancer, The levamisol group show less deaths (15% versus 30%), less relapses (15% versus 20%) and less metastases (10% versus 30%). In the Colon Cancer, the levamisol group show more toxicity grade according to WHO classification than folinic acid group (44% versus 32%), although never beyond grade 2, The gastrointestinal toxicity was greater in the levamisol group (32% versus 16%) and also the hematological toxicity was greater in this group (32% versus 24%). In Rectal cancer, toxicity was below grade 2. Gastrointestinal toxicity was greater in the levamisol group (15% versus 5%). Hematological toxicity was similar in both groups of rectal cancer (50%). In colon cancer, Global Survival was greater in the folinic group than in the levamisol group (88% versus 84%). On the other hand, in the rectal cancer, the global survival was greater in the levamisol group (88% versus 70%). Disease-free Survival was greater in the folinic acid group (72% versus 60%) in the colon cancer. In the rectal cancer, the disease-free survival was greater in the levamisol group (60% versus 40%). Conclusion: Oral treatment results in few side effects and low toxicity, improve quality of life of patients and make the survival. substantial.
6343 LOCALIZATION OF THIOREDOXIN REDUCTASE MRNA IN COLORECTAL CANCER TISSUE BY IN-SITU HYBRIDIZATION. Sandra Lechner, Wibke Ballhom, Ulf Mueller-Ladner, Christopher Benzing, Juergen Schoelmerich, Frauke Bataille, Josef Rueschoff, Frank Kullmann, Dept of Internal Medicine I, Univ of Regensburg, Regensburg, Germany; Dept of Pathology, Univ of Regensburg, Regensburg, Germany; Dept of Pathology, Kassel, Germany. Background: Thioredoxin (Trx) and thioredoxin reductase (TR) are redox proteins that have been implicated in cellular events like proliferation or apoptosis. Trx-mRNA has been reported to be upregulated in several human tumors. Thus, the TR-Trx system could play an important role in regulating cell growth and death. Therefore we analyzed the expression and location of TR in a series of colon cancer tissues by in situ hybridization. Methods: Quantitative RT-PCR was performed using gene specific primers for TR in order to quantify the amount of TR mRNA in different cell lines. TR RNA probes were labelled with digoxigenin-UTP. Hybridization was performed overnight at 50°C. To detect TR mRNA, an anti-digoxigenin antibody was applied. Experiments were performed using matched pairs of normal and colon cancer or adenoma tissue, and colon tissue from a patient with Crohn's disease. Results: The colon cancer cell lines HCT-15 and LoVo expressed much more TR-mRNA than HT-29 or SW480. Furthermore, 23132/87- (gastric cancer), A549- (lung cancer) and HT1080- (fibrosarcoma) cells expressed high levels of TR-mRNA, whereas BT20(breast cancer) and Caki 1- (kidney cancer) cells expressed neglectable amounts of TR-mRNA. All tissue sections (normal, inflammatory and neoplastic) showed a positive hybridization signal for TR-mRNA. Positive cells were found between, but not within the colon crypts. None of the epithelial cells were positive for the TR-probe, whereas more than 70% HT29 cells were positive. By immunhistochemistry we could show that the in situ positive cells were CD68 and CD45 negative, but some of them were CD3 positive. A high number of TR-positive cells were found in inflammatory infiltrates of Crohn's disease. Colon cancer tissues showed a frequent number of TR-RNA positive cells in non-neoplastic areas, but an reduced number of TR-positive cells in preneoplastic or neoplastic areas. Conclusions: In colon cancer tissue TR is expressed by lymphocytes (CD3 positive) and other cells e.g. granulocytes. In contrast to the cell culture experiments, colon epithelial cells (neoplastic or non-neoplastic) were not positive for TR-mRNA probe. It is quite possible that the loss of cell-cell interactions in cell culture leads to e.g. a stress induced upregulation of TR-mRNA. The decrease ofTR-positive cells between crypts in neoplastic areas is remarkable and implicates that the loss of TR might contribute to tumor promotion by reduced defense mechanisms. This research was funded by the DFG (Ku 1024/6-1, Mu 138311-1)
6345 MUCOUS PHENOTYPIC EXPRESSION OF GASTRIC ADENOCARCINOMA IN KOREA. Ok-Jae Lee. Woo-Song Ha, Hidenobu Watanabe, Gyeong-sang National Univ Coli of Medicine, Chinju, South Korea; Niigata Univ Sch of Medicine, Niigata, Japan. Background!Aim: Histochemical and immunohistochemical studies for mucin contained in tumor allowed the mucous phenotypic classification of gastric adenocarcinomas. We investigated the mucous phenotypic expression of Korean gastric adenocarcinomas and its relationships with clinical and histopathological characteristics. Methods: Histochemical and immunohistochemical stainings for paradoxical concanavalin A, MUC5AC, MUC-2 glycoprotein and CDIO were performed in 74 surgically obtained gastric adenocarcinomas. Results: Among 74 gastric adenocarcinomas, 30 (40.5%) expressed gastric phenotype(lO foveolar and 20 foveolo-glandular), 20 (27.0%) intestinal phenotype(7 complete and 13 incomplete), 15 (20.3%) mixed gastric-intestinal phenotype and 9 (12.2%) undetermined type. The gastric and gastric predominant types were 54.1% (40/74), and intestinal and intestinal predominant types 31.1% (23/74). No relationship between mucous phenotypic expression and tumor location was found. Among 21 papillary and tubular adenocarcinomas, 5 (23.8%) expressed predominantly gastric phenotype and 12 (57.1%) intestinal phenotype. Among 53 poorly differentiated adenocarcinomas, signet ring cell carcinomas and mucinous adenocarcinomas, 35 (66.0%) were gastric predominant and II (20.8%) were intestinal predominant phenotypes. 35 out of 40 (87.5%) gastric predominant cancers were poorly differenciated, signet ring cell or mucinous adenocarcinomas. Helicobacter pylori infection rates were 87.5%, 91.3%, and 66.7% in gastric predominant, intestinal predominant, and undetermined phenotypes, respectively. Conclusions: Korean gastric adenocarcinomas expressed predominantly gastric phenotype and there was no association between mucous phenotypic expression and tumor location. However, mucous phenotype may be associated with differentiation of gastric adenocarcinoma and Helicobacter pylori infection.
6346 UNCOUPLING PROTEIN-2 EXPRESSION IN HUMAN HEPATOCELLULAR CARCINOMA. Fung-Yee J. Lee, Paul Bs Lai, Alexender Lau, Siu-Man Ng, Ursula Pf Chan, Shali Shen, Wan-Yee Lau, Cuhk, Hong Kong, Hong Kong. Background: Previous studies have demonstrated that uncoupling protein-2 (UCP-2) gene expression can be induced by tumor necrosis factor (TNF) and lipids. As the level ofTNF secretion increased during the development of cirrhosis, UCP-2 gene expression is induced (unpublished data). In our locality, the majority of hepatocellular carcinoma (HCC) develop in hepatitis B-related cirrhosis, the expression of UCP-2 gene in human HCC is unknown. The aim of this study is to evaluate the expression of UCP-2 gene in human hepatocellualr carcinoma. Methods: Forty-six hepatitis B carriers with histologially confirmed HCC were included in the present study. Tissues collected from the resected liver specimen, including the tumor and the non-tumorous portions were snap-frozen in liquid nitrogen. Total RNA was extracted and semi-quantitative RT-PCR using the human