Effects of lanreotide on the healing of small bowel anastomoses following obstructive ileus in rats.

PURPOSE: Lanreotide, a long-acting somatostatin analogue, inhibits intestinal, bile and pancreatic secretions and decreases intestinal motility. The purpose of this experimental study was to evaluate the effects of lanreotide on the healing of intestinal anastomoses following small bowel obstruction. METHODS: Two groups of 16 Wistar rats (average weight 310 g) were used. Basal diameters of ileus were measured prior to the ligation of the bowel, 15 cm from the ileocecal valve. Luminal fluid was also withdrawn proximal to the obstructed bowel for sodium and potassium analysis. Lanreotide was administered intramuscularly in a single dose (5.4 mg/kg) in the first group, while the same volume of saline was used in the control group. 48 h later rats were re-operated upon. Diameters of the obstructed segments were measured, and luminal fluid of the obstructed bowel was withdrawn and sodium and potassium levels were measured. A segment of 1 cm of the obstructed bowel was resected and end-to-end intestinal anastomosis was performed. Rats were sacrificed on day 7 following the second operation. Anastomoses were examined macroscopically and resected including a 2.5 cm of small bowel on either side. Bursting pressures were measured and the specimens were send for histological examination. RESULTS: The diameter of obstructed bowel increased significantly in both groups. The increase was more prominent in the control group (P < 0.001). Total luminal electrolyte contents for sodium and potassium were stastistically higher in the control group compared to the lanreotide group (P < 0.001). Adhesion formation was more extensive in the control group. Bursting pressures were significantly higher in the lanreotide group compared to the control group (P=0.003). Histological examination of anastomoses showed a more profound inflammatory reaction in the control group compared to the lanreotide group while microscopical healing of the anastomoses was almost the same in both groups. CONCLUSIONS: Lanreotide administration in rats with small bowel obstruction decreases significantly distension and electrolyte losses and seems to improve strength of small bowel anastomoses.

Effect of early versus delayed postoperative injection of 5-fluorouracil plus interferon-alpha on colonic healing.

The purpose of this study was to determine whether delayed, postoperative, intraperitoneal treatment with 5-fluorouracil (5-FU) plus interferon-alpha-2a (IFN) has adverse effects on colonic healing, as does early treatment. Seventy male Wistar rats underwent colonic anastomoses. The rats were randomized to one of four groups. Early intraperitoneal injection was given to groups 1 and 2 which was repeated once daily for the first 3 postoperative days. Treatment was delayed in groups 3 and 4, from the 4th to the 7th postoperative day. A 0.9% NaCl solution was injected in the rats of control groups 1 and 3. In groups 2 and 4, we infused 5-FU (20 mg/kg/day) and IFN (45,000 IU/kg/day). All the animals were sacrificed on the 8th postoperative day. The anastomotic rupture rate was significantly higher in the rats of group 2 compared to control group 1 (p < 0.05), while there were no differences between groups 3 and 4 (p > 0.05). Abscess formation and adhesions were more frequent in group 2 compared to control group 1, while no differences were observed between groups 3 and 4. Anastomotic bursting pressure was statistically significantly lower in the rats of group 2 compared to group 1 (p < 0.05); no differences were noticed between groups 3 and 4 (p > 0.05). Simultaneous histologic evaluation showed a more profound inflammatory reaction and delayed anastomotic healing in group 2 compared to control group 1; there were, however, no differences between groups 3 and 4. In conclusion, the immediate, postoperative, intraperitoneal injection of 5-FU plus IFN impairs colonic healing while delayed treatment (starting on the 4th postoperative day) has no adverse effects on wound healing.

Colonic healing after early intraperitoneal administration of 5-fluorouracil and interferon in rats.

The aim of this experimental study was to investigate whether the intraperitoneal perioperative injection of 5-flurouracil (5-FU)--with or without the addition of interferon (INT)--influences colonic healing. We used 57 male Wistar rats which were subjected to anastomosis of the colon. Intraoperatively, the rats were randomised into one of three groups. The rats in the control group (group 1, n = 15) received a 0.9% NaCl solution; the rats in group 2 (n = 21), 5-FU (20 mg/Kg/day), and those in group 3 (n = 21), 5-FU (20 mg/Kg/day) plus INT (45,000 IU/Kg/day). These drugs were injected intraperitoneally during the operation and once daily for the next two days. The rats were sacrificed on post-operative days 3, 5 or 8. The rupture rate of the anastomoses was statistically significantly higher in groups 2 and 3, compared with the control group (P < 0.05); no differences were observed between groups 2 and 3. Abscess and adhesion formation were more marked in groups 2 and 3 than in the control group; however no differences were recorded between groups 2 and 3. The anastomotic bursting pressure was statistically significantly lower in groups 2 and 3 compared to the control group (P < 0.05), on post-operative days 5 and 8; however, no differences were measured between groups 2 and 3. Histologic evaluation also showed a more profound inflammatory response in groups 2 and 3, compared with group 1. In conclusion, the intraperitoneal, intraoperative administration of 5-FU hinders colonic healing in rats. The additional intraperitoneal injection of interferon does not seem to aggravate this adverse effect.

Influence of intraperitoneal 5-fluorouracil plus folinic acid on the healing of colonic anastomoses in rats.

We studied the effects of intraperitoneal 5-fluorouracil (5-FU) administration with or without the addition of folinic acid (FA) on the healing of colonic anastomoses in rats immediately after surgery. Sixty-three male Wistar rats were subjected to colonic anastomosis. During surgery, the rats were randomized into one of three groups. Therapy was administered as an intraoperative intraperitoneal injection which was repeated once daily for the first 2 postoperative days. A 0.9% NaCl solution was administered to the rats in the control group. In group 2, we injected 5-FU (20 mg/kg/day) and in group 3 5-FU (20 mg/kg/day) plus FA (2 mg/kg/day). The rats were sacrificed on postoperative days 3, 5 or 8. Rupture of the anastomosis was significantly higher in the rats of groups 2 and 3, compared with the control group (p < 0.05). There were, however, no differences between groups 2 and 3. Formation of adhesions and abscesses was more common in groups 2 and 3 than in the control group for all study days. A significant difference in the anastomotic bursting pressure was measured for the control group in comparison to groups 2 and 3 on days 5 and 8 (p < 0.05). Histologic evaluation also showed a more profound inflammatory reaction and delayed healing of the anastomoses in groups 2 and 3, compared to the control group. Therefore, the perioperative intraperitoneal administration of 5-FU can inhibit the healing of colonic anastomoses in rats. The addition of an intraperitoneal injection of FA does not aggravate this negative effect.