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Background and Aim: Octreotide is considered to reduce exocrine pancreatic secretion in acute hemorrhagic necrotizing pancreatitis decreasing pancreatic autodigestion. The aim of this study was to determine whether octreotide also has antioxidative effects in acute pancreatitis. Additionally time and dose of application were of interest., Method: Ninety male Sprague-Dawley rats were randomized into six groups (n = 15). Group 1 underwent a laparotomy, and animals in groups 2-6 received intraductal glycodeoxycholic acid followed by intravenous cerulein. Groups 3 and 4 were injected with 0.5 mg octreotide, while groups 5 and 6 received continuous intravenous infusion of 0.05 mg octreotide/h for 10 h. Treatment was initiated 6 hours after induction of pancreatitis (IP) in groups 3 and 5, and 14 h after IP in groups 4 and 6. At 24 h after IP all animals were killed and each pancreas was analyzed histopathologically. In addition, levels of pancreatic lipid peroxidation protective enzymes glutathione-peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as lipid peroxidation via thiobarbituric acid reactive substances (TBARS) were determined., Results: Early bolus application of octreotide reduced severity of histopathological changes in acute pancreatitis and decreased lipid peroxidation in pancreatic tissue samples; however, late bolus application and continuous intravenous infusion did not influence pancreatitis or lipid peroxidation., Conclusion: Octreotide seems to have a dose- and time-dependent effect on histopathology and lipid peroxidation in a model of pancreatitis in rats.

Background: There is controversial discussion whether metastasis initiated by laparoscopy with carbon dioxide might be prevented by instillation of taurolidin or radical scavengers like the somatostatin analogue Octreotide. Therefore we evaluated the effects of laparoscopic lavage with taurolidin and Octreotide on liver metastasis after staging laparoscopy in ductal pancreatic cancer., Methods: In 60 Syrian hamsters pancreatic adenocarcinoma was induced by weekly subcutanous injection of 10 mg N-nitrosobis-2-oxopropylamin/kg body weight for 10 weeks. In the 16th week laparoscopic staging biopsy by use of carbon dioxide was performed. Finally animals underwent abdominal irrigation with saline (gr.1, n = 20), taurolidin (0.5%) (gr.2, n = 20) or Octreotide (gr.3, n = 20). In week 25 animals were sacrificed, pancreas and liver were analysed., Results: Size of pancreatic carcinomas was decreased in the taurolidin gr. compared to the other two groups. Furthermore the number of liver metastasis per animal was reduced after lavage with taurolidin (2 +/- 2) and Octreotide (2.5 +/- 2) compared to saline irrigation (4 +/- 4) (p < 0.05). Additionally the incidence of port site metastases was significantly reduced in the taurolidin group. Activity of antioxidative enzyme superoxide dismutase (SOD) was increased while concentration of products of lipidperoxidation was decreased in non-metastatic liver after taurolidin irrigation compared to saline or Octreotide irrigation., Conclusions: Taurolidin irrigation during laparoscopy might be a new concept to reduce the number of liver metastasis and port site metastases in pancreatic cancer.

Irrigation with taurolidine after laparoscopy decreases tumor growth in colon carcinoma. In pancreatic cancer subcutaneous therapy with octreotide decreases oxidative stress and carcinogenesis as well. However, it is still unclear, whether irrigation with taurolidine or octreotide after laparoscopic pancreatic biopsy reduces tumor growth in pancreatic cancer as well. In 60 Syrian hamsters ductal pancreatic adenocarcinoma was induced by weekly injection of 10mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. In week 16 laparoscopic pancreatic biopsy by use of carbon dioxide was performed (gr. 1, n = 20) with subsequent laparoscopic irrigation with taurolidine (gr. 2, n = 20) or octreotide (gr. 3, n = 20). In week 25 hamsters were sacrificed. Our results show that macroscopic visible primary tumors were found in only one animal of the taurolidine group (5.9%), compared to 42.1% in the saline and 62.5% in the octreotide group (P<0.05). Carcinomas were smaller after saline (6+/-23 mm(2)) than after octreotide irrigation (70+/-120 mm(2), P<0.05). In conclusion this study showed that laparoscopic irrigation with taurolidine after pancreatic biopsy inhibited tumor growth in ductal pancreatic adenocarcinoma.

Background: The therapeutic effects of octreotide in acute hemorrhagic necrotizing pancreatitis (ANP) have always been considered to be due to the inhibition of the exocrine pancreatic secretion in order to reduce pancreatic autodigestion. In this experimental study we analyzed whether octreotide has also antioxidative effects on acute pancreatitis., Methods: 40 male Wistar rats were randomized into four groups (n = 10). Group 1 underwent a laparotomy. Groups 2-4 received an injection of natrium taurocholate into the pancreatic duct to induce acute pancreatitis. One hour later group 2 was injected 1 ml NaCl solution intraperitoneally, while groups 3 and 4 received 0.1 or 0.2 mg octreotide, respectively. The severity of ANP was examined histologically. The lipid peroxide level as well as the activity of glutathione peroxidase and superoxide dismutase were measured in plasma and pancreatic tissue samples., Results: High-dose octreotide decreased the lipid peroxide level in plasma (2.1 +/- 0.53 vs. 4.69 +/- 1.35 nmol/l; p < 0.05) and pancreatic tissue samples 4.67 +/- 1.37 vs. 13.20 +/- 2.93 nmol/ml; p < 0.05) compared to the pancreatitis control group. Low-dose octreotide, however, did not reduce lipid peroxidation., Conclusion: Octreotide seems to have a dose-dependent antioxidative effect in natrium taurocholate-induced pancreatitis in rats.

Port site metastasis is a dreadful event following laparoscopy; however, the exact pathomechanism is still unknown. In order to prevent trocar metastasis we determined the effects of intraperitoneal lavage with either taurolidine or octreotide on port site and liver metastasis after laparoscopy in a chemically induced, solid pancreatic adenocarcinoma. Pancreatic adenocarcinoma was induced in 60 Syrian hamsters by weekly injection of 10 mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. Six weeks later, a laparoscopic pancreatic biopsy was performed by the use of a pneumoperitoneum with carbon dioxide (12 mm Hg), followed by an abdominal irrigation with 5 ml normal saline (group 1, n = 20), 5 ml 0.5% taurolidine (group 2, n = 20) or 5 ml octreotide (20 mg/ml) (group 3, n = 20). After 8 weeks, all hamsters were sacrificed and histopathologically examined. There was only one macroscopic visible primary tumor in the taurolidine group (5.9%), compared to 42.1% in the saline group and 62.5% in the octreotide group (P < 0.05). The size of carcinomas was smaller in the saline group than after octreotide irrigation (median 6, range 2-25 vs. median 70, range 40-160 mm2, P < 0.05). The number of liver metastases per animal was increased after saline irrigation (median 4, range 2-6), compared to taurolidine (median 2, range 1-3) or octreotide (median 2.5, range 2-4) (P < 0.05). Port site metastases were found in 36.8% after saline, in 37.5% after octreotide and in 0% after taurolidine irrigation (P < 0.05). Thus port site metastasis was effectively prevented by taurolidine irrigation after staging-laparoscopy in pancreatic cancer.

Introduction: In prospective clinical trials, octreotide improved quality of life and survival time in patients with pancreatic cancer., Aims: To analyze whether octreotide modulates the hepatic oxygen radical metabolism and thus might decrease liver metastasis in an animal model of pancreatic cancer., Methodology: Syrian hamsters received 0.9% NaCl or N-nitrosobis(2-oxopropyl)amine (BOP) for 3 months. Therapy was performed for 12 weeks by 0.9% NaCl or octreotide. Hamsters received a standard diet (3.5% fat) or were fed a high-fat diet (21.4% fat). In the 25th week, the pancreas and liver were examined macroscopically and histologically. The level of lipid peroxidation and activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined intrahepatically., Results: The number of liver metastases per animal and the size of liver metastases were increased by the high-fat diet, whereas they were decreased by octreotide. Octreotide increased activities of GSH-Px and SOD. The concentration of thiobarbituric acid reactive substances was increased by BOP and a high-fat diet and decreased by octreotide., Conclusion: Octreotide decreases the number and size of liver metastases in chemically induced pancreatic cancer in Syrian hamsters. This is accompanied by high hepatic GSH-Px and SOD activity and a low level of lipid peroxidation.

Objectives: In prospective clinical trials, octreotide improved the quality of life and survival time in patients with pancreatic cancer. In this study, we analyzed whether octreotide modulates the intrametastatic oxygen radical metabolism and might decrease liver metastasis in a model of pancreatic cancer., Methods: Syrian hamsters received 0.9% NaCl or N-nitrosobis(2-oxopropyl)amine for 3 months. Therapy was performed for 12 weeks by 0.9% NaCl or octreotide. Hamsters received a standard diet or were fed a high-fat diet. In the 25th week, pancreas and liver were examined macroscopically and histologically. The level of lipid peroxidation and the activity of glutathione peroxidase and superoxide dismutase were determined intrahepatically and intrametastatically., Results: The number and size of liver metastases per animal were increased by high-fat diet and decreased by octreotide. While high-fat diet increased intrahepatic extrametastatic lipid peroxidation, octreotide decreased intrahepatic extrametastatic lipid peroxidation and increased intrametastatic lipid peroxidation., Conclusions: Octreotide decreases the number and size of liver metastases in chemically induced pancreatic cancer in Syrian hamsters. Possible mechanisms are the prevention of high lipid peroxidation in non-metastatic liver as well as the increase in intrametastatic lipid peroxidation, leading to loss of integrity of spread tumor cells., (Copyright 2001 S. Karger AG, Basel)

In prospective clinical trials single octreotide therapy or combined therapy with tamoxifen has improved the quality of life and survival time in patients with pancreatic cancer. In this study we analyzed the influence of octreotide and tamoxifen on tumor growth and liver metastases in chemically induced pancreatic adenocarcinoma in Syrian hamsters. Octreotide alone and the combined therapy (octreotide/tamoxifen) decreased the incidence of macroscopic pancreatic carcinomas as well as the number and size of liver metastases. The combined therapy showed no superior effect to octreotide alone. Furthermore, there was no difference between the tamoxifen and the control group., (Copyright 2001 S. Karger AG, Basel)