Influence of 5-fluorouracil and folinic acid on colonic healing: An experimental study in the rat

Graf, Wilhelm; Weiber, S; Glimelius, Bengt; Jiborn, H; Påhlman, Lars; Zederfeldt, B

doi:10.1002/bjs.1800790840

Cited by 55 publications

(61 citation statements)

References 13 publications

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“…On the 7th PO day, bursting pressure values in the IV 5-FU group were significantly lower than the IP group. Similar results have been found in previously reported studies [22,32,33] . Graf et al [32] reported that early postoperative 5-FU administration had a negative impact on the bursting strength of colonic anastomosis.…”

Section: Discussionsupporting

confidence: 93%

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Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

Özel

Özel²,

Toros³

et al. 2009

WJG

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AIM:To determine the effect of chemotherapy on wound healing by giving early preoperative 5-fluorouracil (5-FU) to rats with colonic anastomoses. METHODS:Sixty Albino-Wistar male rats (median weight, 235 g) were used in this study. The rats were fed with standard laboratory food and given tap water ad libitum . The animals were divided into three groups:Group 1: Control group (chemotherapy was not administered), Group 2: Intraperitoneally (IP) administered 5-FU group (chemotherapy was administered IP to animals at a dose of 20 mg/kg daily during the 5 d preceeding surgery), Group 3: Intravenously (IV) administered 5-FU group. Chemotherapy was administered via the penil vein, using the same dosing scheme and duration as the second group. After a 3-d rest to minimize the side effects of chemotherapy, both groups underwent surgery. One centimeter of colon was resected 2 cm proximally from the peritoneal reflection, then sutured intermittently and subsequently end-to-end anastomosed. In each group, half the animals were given anaesthesia on the 3rd postoperative (PO) day and the other half on the 7th PO day, for in vivo analytic procedures. The abdominal incisions in the rats were dissected, all the new and old anastomotic segments were clearly seen and bursting pressures of each anastomotic segment, tissue hydroxyproline levels and DNA content were determined to assess the histologic tissue repair process. RESULTS:When the IV group was compared with the IP group, bursting pressures of the anastomotic segments on the 3rd and 7th PO days, were found to be significantly decreased, hydroxyproline levels at the anastomotic segment on the 7th PO day were significantly decreased (P < 0.01). CONCLUSION:In this study, we conclude that early preoperative 5-FU, administered IV, negatively affects wound healing. However, IP administered 5-FU does not negatively affect wound healing.

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Section: Discussionsupporting

confidence: 93%

“…All rats lost weight compared with baseline values during 5-FU administration and after the operation, which was statistically significant in the IV group. These results were concordant with reports from the literature [6,8,32] . Weight loss after 5-FU is related to anastomotic healing.…”

Section: Discussionsupporting

confidence: 93%

Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

Özel

Özel²,

Toros³

et al. 2009

WJG

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“…In addition, an experimental study showed an impaired healing after i.p. 5-FU, but when folinic acid was added, no further deterioration occurred (Graf et al, 1992). However, this problem and other chemotherapy-related toxicities have been investigated in several clinical studies and this form of administration has not been associated with an increased complication rate (Graf et al, 1994c;Vaillant et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Improved survival in patients with peritoneal metastases from colorectal cancer: a preliminary study

et al. 2004

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Patients with peritoneal or local metastases from colorectal cancer have a poor prognosis. However, aggressive treatments by debulking surgery and infusional intraperitoneal (i.p.) chemotherapy have been tried and appear to benefit selected patients. We assayed the effects of debulking surgery and i.p. chemotherapy with respect to survival and compared the results with matched control patients treated by intravenous (i.v.) chemotherapy. In all, 18 patients with peritoneal and/or local metastases from colorectal adenocarcinoma underwent debulking surgery followed by 5-fluorouracil (5-FU) 550 mg m À2 day À1 i.p. and leucovorin (LV) 60 mg m À2 day À1 i.v. The chemotherapy was started the day after surgery and was given daily for 6 days and repeated monthly for totally eight courses. The control patients, matched for age, gender, performance status and metastatic site, were randomly selected from controlled clinical chemotherapy trials and treated with i.v. 5-FU þ LV or i.v. methotrexate þ 5-FU þ LV. There was no treatment-related mortality. The median survival among i.p. patients was 32 months compared to 14 months in the control group. In all, 11 patients who underwent macroscopically radical surgery had a longer survival than those who were not radically operated (P ¼ 0.02). These results indicate that patients with peritoneal metastases and/or locally advanced cancers but without distant metastases may benefit from cytoreductive surgery combined with i.p. chemotherapy.

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“…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. Collagen synthesis was measured in three groups of animals (n = 6): a control group, a 5-FU group and a group which received 5-FU plus levamisole.…”

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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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Influence of 5-fluorouracil and folinic acid on colonic healing: An experimental study in the rat

Cited by 55 publications

References 13 publications

Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

Improved survival in patients with peritoneal metastases from colorectal cancer: a preliminary study

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

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