Is Circular Fibrin Sealing of Low Rectal Anastomosis Able to Prevent Leakage in 21-Day Follow-up? Randomized Experimental Trial in Pigs.

Purpose. Clinically apparent anastomotic leakage (AL) after low anterior rectal resection (LAR; <7 cm from anal verge) using circular double-stapled anastomosis without defunctioning stoma is up to 37.5%. However, it is unclear whether there is reduction of LAR after 21 postoperative days without defunctioning stoma but with extraluminal anastomotic application of fibrin sealant. Methods. Forty-eight-week-old pigs underwent LAR and circular double-stapled anastomosis in end-to-end technique (descendo-rectostomy). Animals were randomized into therapy and control group (cg). Therapy group (n = 20) received additional extraluminal circular anastomotic application of fibrin sealant. Objective was to assess incidence of clinically apparent and nonclinically apparent leakage through the 21st postoperative day. Remaining animals were sacrificed on the 21st day, and anastomotic region was analyzed. In case of earlier diagnosed AL, animals were sacrificed. Results. In cg, we observed clinically and nonclinically AL in 20% (n = 4). No animal was identified with a nonclinical-apparent leakage in this group, and all 4 animals with leakages presented clinical signs. In the therapy group, no animal (0/20) developed clinically apparent leakage signs. There were no leakages in this group, but 3 animals had ulcerative lesions without leak and without clinical signs. These lesions were observed intraluminally at crossing of staple lines after 21 days. In one of these animals, incomplete leakage was observed, blocked by fibrin sealant. Conclusion. In circular stapled colorectal anastomosis, circular fibrin glue sealant successfully protected anastomotic intraluminal wall defects at crossing of staple lines, reducing leakage rate from 20% to 0% (cg vs therapy group) after 21 postoperative days.

Fish oil, but not soy bean or olive oil enriched infusion decreases histopathological severity of acute pancreatitis in rats without affecting eicosanoid synthesis.

Different dietary fatty acids affect eicosanoid metabolism in different ways, thus influencing the pro- and anti-inflammatory balance of prostaglandins and leukotrienes. Therefore, we analyzed the impact of [n-3], [n-6], and [n-9] fatty acids on eicosanoid metabolism and histopathology in acute pancreatitis in rats. Seventy-five male Sprague-Dawley rats were randomized into five groups (n = 15). Group 1 underwent only laparotomy, while in groups, 2-5 pancreatitis was induced. Groups 1 and 2 were then given saline infusion, groups 3-5 received fat emulsion (group 3: rich in [n-6], group 4: rich in [n-9], group 5: rich in [n-3] fatty acids) for another 18 h. Infusion rich in [n-3] fatty acids significantly decreased histopathological severity of pancreatitis, compared to all other groups. There was no difference concerning the concentrations of prostaglandins and leukotrienes between all groups. Parenteral infusion rich in [n-3] fatty acids reduced histopathological severity of acute pancreatitis in rats without changing eicosanoid metabolism at the endpoint.

Early inhibition of prostaglandin synthesis by n-3 fatty acids determinates histologic severity of necrotizing pancreatitis.

OBJECTIVE: Previously, we observed decreased histopathological severity of acute necrotizing pancreatitis (ANP) by parenteral nutrition with n-3 fatty acids. Thus, we now sequentially analyzed the impact of n-3 fatty acids on prostaglandin and leukotriene synthesis in ANP. METHODS: One hundred ninety-eight Sprague-Dawley rats (11 groups, n = 18) underwent intraductal glycodesoxycholat instillation and 6-hour cerulein infusion. Afterward, saline was infused in groups 2, 4, 6, 8, and 10, whereas groups 3, 5, 7, 9, and 11 received infusion rich in n-3 fatty acids (Omegaven, Fresenius Kabi, Bad Homburg, Germany). Animals were killed after 6 (group 1), 10 (groups 2 and 3), 14 (groups 4 and 5), 18 (groups 6 and 7), 22 (groups 8 and 9), and 26 hours (groups 10 and 11). The pancreas was histopathologically examined, and the pancreatic eicosanoid metabolism (prostaglandin E2, prostaglandin F1alpha [PGF1alpha], and leukotrienes) and lipid peroxidation (thiobarbituric acid-reactive substance, superoxide dismutase, and glutathione peroxidase) were analyzed. RESULTS: Between the 14th and 26th hours, histopathologic scores (edema, inflammation, bleeding, and necrosis) were reduced in the n-3 fatty acid group compared with the corresponding saline group. Pancreatic prostaglandin E2 and PGF1alpha were decreased between the 10th and 18th hour by n-3 fatty acids; PGF1alpha was reduced after 26 hours compared with the corresponding saline group. Lipid peroxidation was decreased by n-3 fatty acids after 14 hours (thiobarbituric acid-reactive substance); however, there was no difference concerning lipid peroxidation protective enzymes (glutathione peroxidase and superoxide dismutase). CONCLUSIONS: Parenteral therapy with n-3 fatty acids decreased histopathologic severity in ANP by early inhibition of prostaglandin (E2 and F1alpha) synthesis and reduction of lipid peroxidation.

Effects of octreotide in acute hemorrhagic necrotizing pancreatitis in rats.

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.

Impact of taurolidin and octreotide on liver metastasis and lipid peroxidation after laparoscopy in chemical induced ductal pancreatic cancer.

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.

Effects of octreotide on lipid peroxidation in pancreas and plasma in acute hemorrhagic necrotizing pancreatitis in rats.

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.