Post-operative levamisole may compromise early healing of experimental intestinal anastomoses (original) (raw)
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British journal of cancer, 1996
The continuing search for effective adjuvant therapy after resection of intestinal malignancies has prompted a growing interest in both immediate post-operative regional chemotherapy and the combination of 5-fluorouracil (5-FU) and interferon-alpha as drugs of choice. We have compared the effects of both compounds, alone and together, on early healing of intestinal anastomoses. Four groups (n = 26 each) of rats underwent resection and anastomosis of both ileum and colon: a control group and three groups receiving intraperitoneal 5-FU, interferon-alpha or both on the day of surgery and the next 2 days. Animals were killed 3 or 7 days (n = 10 each) after operation in order to measure anastomotic strength and hydroxyproline content. The remaining six animals in each group were used to study anastomotic collagen synthetic capacity at day 3. Three days after operation, ileal anastomotic bursting pressure was lowered by 37% in the 5-FU/interferon-alpha group (P = 0.0104). At day 7, anasto...
Surgery Today, 1999
In this study, the effects of intraperitoneal 5-fluorouracil (5-FU), cisplatinum (Cis), adriamycin (Adr), and methotrexate (MTX) administration on rat intestinal anastomosis were compared. Cis and MTX led to significant weight loss in the first 5 days compared with the control group. Within 14 days all rats except the MTX group nearly reached their preoperative weight. No remarkable weight loss or systemic toxicity was observed among the 5-FU and Adr groups. The anastomosis bursting pressure (ABP) at 1 week was significantly lower than that of the control group (P < 0.01 and P < 0.005, respectively). On day 14 the anastomosis bursting pressure in the Cis group was similar to that of the control group but was significantly lower in the MTX group (P < 0.002). Histopathologically, MTX avoided the development of a mucosal layer at the anastomosis site and led to ulcer formation in some of the rats. The ABPs at 7 and 14 days were similar to those in the control group. Neither of the agents had any significant mechanical or histopathologic adverse effects on anastomosis. According to the results of our study, MTX impaired the healing of the anastomosis, and we thus conclude that the intraperitoneal administration of this agent is not safe. On the other hand, Cis showed a detrimental effect on the anastomosis, particularly in the early phase, but this effect disappeared in the late phase. Cis thus should not be administered in the early postoperative phase. As a result, 5-FU and Adr were found to be the safest agents as they did not delay wound healing and did not reduce the anastomotic strength.
International journal of experimental pathology, 1992
Histologic evaluation of intestinal wound healing with and without cytostatics was performed in 36 rats. Variables were the relative position of the wound edges in mucosa and muscularis, necrosis, exudate, granulation tissue, granulocytes, macrophages, fibroblasts, restoration of the mucosal epithelium, and repair of the muscularis propria. The relative position of the wound edges in the mucosa and the muscularis in the initial phase of wound healing depended on technique but appeared to improve in the later phases of wound healing. It was not affected by the administration of antineoplastic agents; neither were muscularis repair, epithelial restoration of the mucosa, necrosis, nor exudate. Granulation tissue, fibroblasts and macrophages were present in maximal amounts after 7 days appearing later or showing this maximum at a different moment in time when antineoplastic agents were given. The processes of epithelial and muscularis repair were not influenced by the relative position ...
Collagenolytic activity in experimental intestinal anastomoses
International Journal of Colorectal Disease, 1992
Collagen degradation is thought to be an integral part of the healing sequence of intestinal anastomoses, but almost nothing is known about the enzyme activities involved. We have studied collagenolytic activities, extracted from I day-old intestinal anastomoses in the rat. Using either soluble type I collagen or fibrillar type I or type III collagen as a substrate, activities measured in extracts from anastomotic segments were compared to those in extracts from uninjured intestine, removed at operation: in all cases, the collagenolytic activity in anastomotic extracts was significantly higher. This increase was significantly more pronounced in large bowel than in small bowel. The activities were strongly inhibited by serum and metallo-chelating compounds. Analysis, by means of SDS-polyacrylamide gel electrophoresis, of the reaction products of the degradation of fibrillar type I collagen by the extracts revealed the presence of a multitude of fragments, amongst them TeA fragments characteristic for the activity of mammalian collagenase. Thus, the degradative capacity towards various collagen substrates is enhanced in the anastomotic area during the first postoperative period and a true mammalian collagenase is one of the enzymes present.
Effect of Levamisole on intestinal anastomoses in transfused guinea pigs
Pediatric Surgery International, 1999
In this experimental study, the eects of an antihelminthic and immunostimulating agent (levamisole) on anastomosis recovery in transfused and normal guinea pigs were investigated. A total of 56 animals were divided into four groups of 14 each; an additional 10 were employed for blood transfusion (BT). Intestinal anastomoses were performed on all animals; the following postoperative treatments were administered: none (control group); BT; intra-abdominal (IA) levamisole; and BT + levamisole. After recording the mortality of each group, a relaparotomy was performed on one-half of the animals on the 3rd postoperative day and on the remaining half on the 7th postoperative day. Findings of IA sepsis, resistance of the anastomosis, bursting pressure, and hydroxyproline values were evaluated. Statistical comparison of the groups was accomplished by analysis of variance. In the transfused group an increase in sepsis was determined and the bursting pressure was signi®cantly lower than in the control group. IA levamisole application following BT reduced the mortality by diminishing IA sepsis and anastomotic abscess formation and increased anastomotic pressure and recovery (P < 0.01). Histopathologic recovery in levamisole groups was better than in the group that received BT only. Levamisole application without BT resulted in equal mortality and morbidity to that of the control group. We conclude that clinical use of levamisole should be considered only in intestinal anastomoses in which BT is inevitable. Key words Intestinal anastomosis á Levamisole á Transfusion Pediatr Surg Int (1999) 15: 488±491 Ó Springer-Verlag 1999 Y.S. Ilhan (8) 1 á C. C Ë ifter á M.A. AkkusË á Z. C Ë etinkaya N. BuÈ lbuÈ ller á M. Erdo gan
Changes in bowel mucosal permeability and wound healing after neoadjuvant chemotherapy
Oncology Letters, 2009
Neoadjuvant chemotherapy (NAC) with 5-fluorouracil (5-FU) and cisplatin (cDDP) is a promising approach for locally advanced gastric cancer. We investigated the influence of nAc with 5-FU/cDDP on the permeability of intestinal mucosa and wound healing. Male sprague Dawley rats were divided into four groups (n=6). group 1 received saline (control group) and groups 2-4 were administered preoperative 5-FU/cDDP (nAc groups). the nAc consisted of daily intraperitoneal administration of 5-FU from day 1 to 5 and from day 8 to 12 and intravenous administration of cDDP on days 2 and 9. the rats underwent gastrotomy (1.0 cm) with a laparotomy of 3 cm in length, under general anesthesia. seven days after surgery, the rats were orally administered with phenolsulfonphthalein (PsP), and the 24-h urinary excretion of PSP was quantified. On postoperative day 8, the bursting pressure (BP) of the gastric suture line and the tensile strength of the abdominal wound were measured. the hydroxyproline (HP) content in the tissue of the abdominal suture line was then measured, and the number of fibroblast cells in the tissue of the gastric suture line was calculated by histopathological examination. The PSP urinary excretion rate was significantly higher in group 2 in comparison with the other groups (P<0.05), while the BP of a selected gastrorrhaphy region was significantly lower in Group 2 (P<0.05). No significant differences were noted in the HP content. nAc with 5-FU/ cDDP disturbs the healing of intestinal anastomoses when the interval between chemotherapy and surgery is insufficient. Neither HP content nor fibroblast counts were correlated with BP. consequently, nAc appeared to affect the remodeling of collagen fiber. Thus, the integrity of the intestine may play a role in intestinal wound healing. 2 Division of surgery, Kouseiren takaoka Hospital, 5-10 eiraku-cho, takaoka 933-8555, Japan