Intraperitoneal cytostatics impair early post-operative collagen synthesis in experimental intestinal anastomosesP6

Martens, M. F. W. C.; Hendriks, T.; Wobbes, Th.; Pont, J.J.H.H.M. de

doi:10.1038/bjc.1992.139

Cited by 24 publications

(19 citation statements)

References 19 publications

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“…For instance, after intraperitoneal administration the median bursting pressure in ileal anastomoses is reduced by 79% in the 5-FU0 group and by 55% in the 5-FU2 group; if delivered intravenously, the median reduction in these groups is 14% and 10% respectively. This agrees well with earlier data, which show that intraperitoneal administration of anti-neoplastic agents leads to a greater reduction of anastomotic collagen synthetic capacity than does intravenous delivery (Martens et al, 1992).…”

Section: Discussionsupporting

confidence: 83%

Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?

et al. 1999

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Early post-operative local or systemic administration of 5-fluorouracil (5-FU) is under investigation as a means to improve outcome after resection of intestinal malignancies. It is therefore quite important to delineate accurately its potentially negative effects on anastomotic repair. Five groups ( n = 24) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving daily 5-FU, starting immediately after operation or after 1, 2 or 3 days. Within each group, the drug (or saline) was delivered either intraperitoneally ( n = 12) or intravenously ( n = 12). Animals were killed 7 days after operation and healing was assessed by measurement of anastomotic bursting pressure, breaking strength and hydroxyproline content. In all cases, 5-FU treatment from the day of operation or from day 1 significantly ( P < 0.025) and severely suppressed wound strength; concomitantly, the anastomotic hydroxyproline content was reduced. Depending on the location of the anastomosis and the route of 5-FU administration, even a period of 3 days between operation and first dosage seemed insufficient to prevent weakening of the anastomosis. The effects of intravenous administration, though qualitatively similar, were quantitatively less dramatic than those observed after intraperitoneal delivery. Post-operative treatment with 5-FU, if started within the first 3 days after operation, is detrimental to anastomotic strength and may compromise anastomotic integrity. © 1999 Cancer Research Campaign

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Section: Discussionsupporting

confidence: 83%

Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?

et al. 1999

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“…A scheduledependent synergism is achieved by injecting 5-fluorouracil plus folinic acid [1,19]. The adverse effect of postoperative administration of 5-fluorouracil on wound healing has been reported in various studies [1,10,[14][15][16][20][21][22][23][24]. In these studies, 5-fluorouracil was administered either as a single drug [20,21] or in combination with other drugs [1,15,[21][22][23][24] and either intravenously [16,20,22,24] or intraperitonally [1,15,21,23,24].…”

Section: Resultsmentioning

confidence: 99%

Healing of Colonic Anastomoses after Immediate and Delayed Administration of 5-Fluorouracil plus Folinic Acid

Kanellos

Kazantzidou²,

Evangelou³

et al. 1998

Eur Surg Res

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The purpose of this experimental study was to investigate whether the delayed, postoperative, intraperitoneal administration of 5-fluorouracil plus folinic acid had adverse effects on wound healing, as did their early administration. Seventy male Wistar rats underwent colonic resection followed by anastomosis of the colon. The animals were randomized into four groups. The rats in control group 1 received a 0.9% NaCl solution intraperitoneally and those in group 2 received 5-fluorouracil (20 mg/kg) plus folinic acid (2 mg/kg) immediately after surgery and for the next 3 days. The rats in control group 3 and those in group 4 received intraperitoneally a 0.9% NaCl solution or 5-fluorouracil plus folinic acid, respectively, from postoperative day 4 to day 7. The rats were sacrificed on the 8th postoperative day. The rupture rate of the anastomoses was statistically significantly higher in group 2 with early treatment compared to control group 1 (p < 0.05); no differences were observed between control group 3 and group 4 with delayed treatment (p > 0.05). Adhesion and abscess formation were more marked in group 2 compared to control group 1; no differences were recorded between groups 3 and 4. The anastomotic bursting pressure was statistically significantly lower in group 2 compared to control group 1 (p < 0.05); no differences were measured between groups 3 and 4. Histologic evaluation showed a more profound inflammatory response and less marked fibroblastic activity in group 2 compared to control group 1; new collagen production was more evident in group 1. No such differences were observed between groups 3 and 4. In conclusion, the immediate, postoperative, intraperitoneal administration of 5-fluorouracil plus folinic acid inhibited wound healing, but delaying chemotherapy (beginning on the 4th postoperative day) had no adverse effects on the healing of colonic anastomoses and can be considered safe.

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“…As a consequence, there exists growing interest in immediate post-operative local adjuvant therapy after resection of intestinal malignancies (Sugarbaker et al, 1990;Sugarbaker, 1994). A number of studies using immediate post-operative intraperitoneal 5-FU are in progress Graf et al, 1994 (Martens et al, 1992a). Daily intraperitoneal administration of 5-FU alone from the day of surgery onwards until sacrifice after 7 days strongly inhibits anastomotic repair in the rat intestine (Graf et al, 1992;de Waard et al, 1995 were killed 3 and 7 days after operation.…”

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confidence: 99%

Post-operative levamisole may compromise early healing of experimental intestinal anastomoses

Waard

Wobbes²,

Man³

et al. 1995

Br J Cancer

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Summary There exists growing interest in immediate post-operative local adjuvant therapy after resection of intestinal malignancies. It is therefore necessary to assess its potential effect on the healing of intestinal anastomoses. Five groups (n = 20) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving intraperitoneal 5-fluorouracil (5-FU), 5-FU plus leucovorin, 5-FU plus levamisole or levamisole alone, on the day of surgery and the next 2 days. Animals were killed 3 or 7 days after operation. Another three groups (n = 6) of animals were used to compare anastomotic collagen synthetic capacity in control rats or rats receiving 5-FU or 5-FU plus levamisole. On the third post-operative day, the average anastomotic bursting pressure in the 5-FU/levamisole group was reduced by 36% as compared with the control group, both in ileum (P = 0.02) and in colon (P = 0.01). Values in the other groups were similar to those in the control group. Anastomotic breaking strength was significantly (P<0.025) lowered in the ileum from the levamisole group at both days 3 and 7. Anastomotic collagen synthetic capacity was strongly reduced in the 5-FU and 5-FU/levamisole groups. However, there was no significant difference between the control group and the four experimental groups with regard to anastomotic hydroxyproline concentration and content, either 3 or 7 days after operation. Thus, limited use of levamisole, alone or in combination with intraperitoneal 5-FU, may compromise intestinal healing.

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Intraperitoneal cytostatics impair early post-operative collagen synthesis in experimental intestinal anastomosesP6

Cited by 24 publications

References 19 publications

Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?

Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?

Healing of Colonic Anastomoses after Immediate and Delayed Administration of 5-Fluorouracil plus Folinic Acid

Post-operative levamisole may compromise early healing of experimental intestinal anastomoses

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