Combined preoperative irradiation and direct postoperative 5-fluorouracil without negative effects on early anastomotic healing in the rat colon

Biert, J.; Wobbes, Theo; Hoogenhout, J.; Man, Boris; Hendriks, T.

doi:10.1016/s0167-8140(96)01844-0

Cited by 15 publications

(14 citation statements)

References 22 publications

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“…Various outcomes have been reported in the studies investigating the effects of 5-FU on wound healing. 31,[37][38][39][40][41][42] Nonetheless, 5-FU is the cytotoxic agent of choice in colorectal cancer CT and has the characteristics of existing on the peritoneal surface for long term and passing into the portal circulation in high amounts. 42 In the present study we used 5-FU together with preoperative RT.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Hyperbaric Oxygen Therapy on Experimental Colon Anastomosis After Preoperative Chemoradiotherapy

Yıldız¹,

Can²,

Yağcı³

et al. 2013

International Surgery

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The aim of the present study was to investigate the effect of hyperbaric oxygen therapy (HBOT) on colon anastomosis after chemoradiotherapy (CRT). Sixty female WistarAlbino rats were divided into 5 groups and underwent left colon resection and end-toend anastomosis. CRT simulation was performed on 2 sham groups before the anastomosis, and 1 of these groups was administered additional postoperative HBOT. Two groups were administered CRT before the anastomosis, and 1 of them received additional postoperative HBOT. On postoperative day 5, all groups underwent relaparotomy; burst pressure was measured and samples were obtained for histopathologic and biochemical analysis. There was a significant weight loss in the CRT groups and postoperative HBOT had an improving effect. Significantly decreased burst pressure values increased up to the levels of the controls after HBOT. Hydroxyproline levels were elevated in all groups compared to the control group. Hydroxyproline levels decreased with HBOT after CRT. No significant difference was observed between the groups regarding fibrosis formation at the anastomosis site. However, regression was observed in fibrosis in the group receiving HBOT after CRT. Preoperative CRT affected anastomosis and wound healing unfavorably. These unfavorable effects were alleviated by postoperative HBOT. HBOT improved the mechanical and biochemical parameters of colon anastomosis in rats.Key words: Anastomosis -Chemoradiotherapy -Hyperbaric oxygen -Rat -Burst pressure 2 Although adjuvant therapy has been a well-accepted procedure to prevent metastasis and local recurrence after surgical resection, more recently neoadjuvant therapy has gained popularity to enable secondary curative resection with clear surgical margin and to prolong overall and recurrence-free survival.2 It has been reported that local recurrence rate is lower, toxicity is rare, and the anal sphincter is more likely to be preserved in those undergoing preoperative radiation. 1,2Despite the current advances in surgical techniques, anastomotic leakage is a severe complication leading to morbidity and mortality after intestinal surgery.3-6 Chemoradiotherapy (CRT) has the potential to lead to inadequate vascularization in tissues, a well-known risk factor for intestinal anastomosis leak. Impaired oxygenation as a result of hampered vascularization may lead to delay in wound healing, which ultimately impairs anastomotic durability. Studies on factors that enhance wound healing to prevent anastomotic leakage in colon anastomosis have been accelerated in the past decade. In a limited number of studies performed for this purpose, hyperbaric oxygen therapy (HBOT), which is applied by means of intermittent inhalation of 100% oxygen under 1 atmosphere pressure, has been reported to have favorable effects on intestinal anastomotic healing.7-9 However, whether HBOT can reverse potential side effects of CRT on would healing and anastomotic durability is unclear. The aim of the present study was to investigate the effects of HBOT on the bioche...

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Section: Discussionmentioning

confidence: 99%

The Effects of Hyperbaric Oxygen Therapy on Experimental Colon Anastomosis After Preoperative Chemoradiotherapy

Yıldız¹,

Can²,

Yağcı³

et al. 2013

International Surgery

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“…Biert et al (29) reported no difference in bursting pressure when irradiation was applied 5 days before surgery. They found stenosis in spite of anastomosis rupture and this overhealing was compensated for by chemotherapy (28). A healing delay only occurred if irradiation was associated with hyperthermia (29).…”

Section: Discussionmentioning

confidence: 99%

“…However, there are still concerns about the healing of rectal anastomoses (17), which had led Minsky et al (18) to recommend a diverting stoma. Conflicting results were also reported in experimental studies using high and moderate doses of irradiation (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Heupel et al (19) and Crowley et al (20) reported a good outcome of colon and small bowel anastomoses, respectively, using a single 500-cGy preoperative dose of irradiation in dogs.…”

Section: Introductionmentioning

confidence: 99%

Preoperative cobalt60 irradiation delays the healing of rectal anastomoses in rats

Chen

Klug

Capelhuchnik

2005

Braz J Med Biol Res

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The healing of colorectal anastomoses after irradiation therapy continues to be a major concern. The authors evaluated the healing of rectal anastomoses in a rat model after a preoperative 500-cGy dose of cobalt 60 irradiation. Thirty-six male Wistar rats were divided into two equal groups: control (group A), and irradiation group (group B). Group B received a single 500-cGy dose of irradiation, and a rectal resection and end-to-end anastomosis was performed in both groups on the 7th day after irradiation. Parameters of the healing process included bursting pressure and collagen content on the 5th, 7th, and 14th days after surgery. In the irradiation group, the mean bursting pressure on the 5th, 7th, and 14th days was 116, 218, and 273 mmHg, respectively. The collagen content assessed by histomorphometry was 9.0, 20.8, and 32%, respectively. In contrast, the control group had a mean bursting pressure of 175, 225 and 263 mmHg, and a collagen content of 17.8, 28.1, and 32.1%, respectively. The adverse effect of irradiation on healing was detectable only on the 5th postoperative day, as demonstrated by lower bursting pressure (P < 0.013) and collagen content (P < 0.008). However, there was no failure of anastomotic healing such as leakage or dehiscence due to irradiation. We conclude that a single preoperative 500-cGy dose of irradiation delays the healing of rectal anastomosis in rats.

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“…During the last 5 days of the irradiation schedule (days [16][17][18][19][20], 5-FU (Fluracedyl 1,000 mg; Pharmachemie, Haarlem, the Netherlands) was administered intraperitoneally through the left lower quadrant of the anterior abdominal wall using a 24 G cannula. Animals received daily either 20 or 10 mg/kg 5-FU.…”

Section: Rct (Days 4-20)mentioning

confidence: 99%

“…Several studies, clinical and experimental, have reported histological changes in the small intestine and colon after RT [13][14][15][16]. Animal studies investigating the influence of combined RCT on colonic anastomosis have yielded conflicting results [17,18]. A limited number of the experimental studies evaluated histologically the effect of preoperative RCT on colonic anastomotic healing.…”

Section: Introductionmentioning

confidence: 99%

Healing of experimental colonic anastomoses: Effects of combined preoperative high‐dose radiotherapy and intraperitoneal 5‐fluorouracil

El-Malt

Ceelen

Broecke

et al. 2001

Intl Journal of Cancer

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SUMMARY To study the effects of preoperative radiochemotherapy (RCT) on the healing of colonic anastomosis, the rectosigmoid colon in male Wistar rats was irradiated up to an end dose of 41.6 Gy (RT) or sham-irradiated (SR). During the last 5 days of the irradiation schedule, 5-fluorouracil (5-FU) was administered intraperitoneally in either a high dose (20 mg/kg, chemotherapy-high dose [CH]) or a low dose (10 mg/kg, chemotherapy-low dose [CL]). Animals were randomly arranged into six groups: group I, control (SR + saline intraperitoneally); group II, RT only; group III, SR + CL; group IV, RT + CL; group V, SR + CH; group VI, RT + CH. Four days after RCT, a side-to-side anastomosis was constructed between the irradiated rectosigmoid and the nonirradiated caecum. Animals were killed 10 days postoperatively. No significant differences were found in the anastomotic bursting pressure or the bursting wall tension. In group VI, mitoses were less (P < 0.01) and mucosal ulceration was more (P = 0.03) pronounced compared to group I. Sclerotic arteries were seen in all irradiated groups and in animals that received high-dose 5-FU alone. 5-FU administration in high or low dose, with or without RT, induced more inflammation in the submucosa compared to controls (P < 0.05). Conclusively, RCT has no detrimental effect on the mechanical strength of colonic anastomosis in this rat model. However, RCT with high-dose 5-FU induces more histological alterations at the anastomotic site.

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Combined preoperative irradiation and direct postoperative 5-fluorouracil without negative effects on early anastomotic healing in the rat colon

Cited by 15 publications

References 22 publications

The Effects of Hyperbaric Oxygen Therapy on Experimental Colon Anastomosis After Preoperative Chemoradiotherapy

The Effects of Hyperbaric Oxygen Therapy on Experimental Colon Anastomosis After Preoperative Chemoradiotherapy

Preoperative cobalt60 irradiation delays the healing of rectal anastomoses in rats

Healing of experimental colonic anastomoses: Effects of combined preoperative high‐dose radiotherapy and intraperitoneal 5‐fluorouracil

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