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

Özel, Leyla; Özel, Melih; Toros, Ahmet Burak; Kara, Muammer; Ozkan, Kemal Sefa; Tellioglu, Gurkan; Krand, Osman; Koyutürk, Meral; Berber, İbrahim

doi:10.3748/wjg.15.4156

Cited by 15 publications

(14 citation statements)

References 39 publications

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“…The majority of studies on anastomosis healing have used hydroxyproline content at the anastomosis site as a measure because it (with proline and glycine) is a component of collagen [10]. In the present study, the level of hydroxyproline was greater in group M than in group C at 7 days postoperatively.…”

Section: Discussionsupporting

confidence: 58%

“…Injections were repeated until the 6th postoperative day (a total of 7). In previous studies, the number of injections ranged from 2 to 7 after surgery [5,6,7,8,10,17]. We chose the maximum number of injection to allow for an adequate contrast in collagen regeneration rates between groups C and M. Because of this, we accepted a higher mortality rate for group M.…”

Section: Methodsmentioning

confidence: 99%

“…In particular, 5-FU has been shown to have a negative effect on the ability of fibroblasts to proliferate and synthesize collagen [4,7,8], which is essential for wound healing after colon anastomosis [9]. On the other hand, various studies have concluded that intraperitoneally administered 5-FU does not affect anastomosis healing [10]. These conflicting results could have been caused by several factors, but we believe that the use of nonstandardized methods was the main contributor.…”

Section: Introductionmentioning

confidence: 99%

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The Use of Collagen Content as Determined by Spectral Domain Polarization-Sensitive Optical Coherence Tomography to Assess Colon Anastomosis Healing in a Rat Model

Son

Jeong²,

Jung

et al. 2014

Eur Surg Res

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Background/Purpose: Many studies have been undertaken to prevent anastomosis leakage of the colon, and several methods have been used to assess anastomosis healing, such as measurement of bursting pressure or hydroxyproline (a marker of collagen) content at the anastomosis site. However, these methods are inappropriate for comparing anastomosis healing at two time points in the same animals. In the present study, we measured the collagen level by spectral domain polarization-sensitive optical coherence tomography (SD-PS-OCT) to assess anastomosis healing. Methods: Sprague-Dawley rats were divided into groups C (saline-administered controls; study group) and M [a 5-fluorouracil (5-FU)-administered experimental group]. Immediately after end-to-end anastomosis of the colon, SD-PS-OCT images of anastomoses were taken (baseline). Animals were administered saline or 5-FU for 7 days. On the 7th postoperative day, SD-PS-OCT images were acquired, a histopathologic exam was performed, and hydroxyproline levels as well as mRNA expressions of collagen-1 and collagen-3 were measured at the anastomosis site. Results: Fibroblast proliferation and inflammatory cell infiltration were greater in group C than in group M. The mRNA expressions of collagen-1 and collagen-3 were substantially higher in group C. Hydroxyproline levels were higher in group M than in group C. Though collagen levels measured by SD-PS-OCT at 7 days were elevated compared with baseline in group C, no such changes were observed for group M. Conclusion: Collagen levels at the colon anastomosis site, measured with SD-PS-OCT, were not increased at 7 days postoperatively versus baseline when 5-FU was injected, but were increased in saline-treated controls. The measurement of collagen content by SD-PS-OCT was found to provide a good means of assessing anastomosis healing, because it allows in situ assessment of collagen contents at baseline and during the postoperative period.

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Section: Discussionsupporting

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Use of Collagen Content as Determined by Spectral Domain Polarization-Sensitive Optical Coherence Tomography to Assess Colon Anastomosis Healing in a Rat Model

Son

Jeong²,

Jung

et al. 2014

Eur Surg Res

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“…24 Ozel et al, Kanellos et al, Morris in their experimental study, concluded that intravenous 5-FU delayed, but did not prevent healing, and that it would be safe to use it in the postoperative period, but not until several days after operation. [25][26][27] In this study seizures was noted in 1 case. This might be due to hypocalcemia and hypomagnesemia in patients that receive intensive chemotherapy, especially cisplatin, with over-hydration.…”

Section: Discussionmentioning

confidence: 84%

Prospective observational study to evaluate the pattern of adverse drug events in cancer patients receiving anti-cancer agents in a tertiary care hospital

Joshi

Kadhe

2016

Int J Basic Clin Pharmacol

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Background: Adverse drug reactions (ADRs) associated with the use of anticancer drugs are a worldwide problem and cannot be overlooked. They range from nausea, vomiting or any other mild reaction to severe myelosuppression. The study was planned to evaluate the pattern of adverse drug events to anti-cancer agents in a tertiary care hospital. Methods: This observational prospective study was carried out in a tertiary care hospital from 1st January 2011 to 31st December 2011. A total of 213 patients who fulfilled the inclusion criteria were enrolled in the study. Out of them, 8 patients were withdrawn from the study as they subsequently underwent radiotherapy. The adverse events observed during the treatment were noted and analyzed by using applicable statistics. Results: Out of 205 patients, 98 were males and 107 were females. Breast cancer was the commonest type of cancer evident. A total 523 anti-cancer drugs were prescribed for the patients with alkylating agents being the most common. 635 adverse events (ADRs) were observed in patients with vomiting and nausea as the most common adverse drug reactions (ADREs). Majority of the ADRs (89%) had a latent onset (occurring 2 or more days after exposure to the drug). Few events were serious in nature (9%); fatal events were uncommon (0.31%). WHO causality was 'possible' for 94% of the events. ADRs were more frequently observed in females in the age group of 46-60 years; mood swings were significantly higher in women, while vomiting was found to be significantly common in men. Conclusions: The study showed that chemotherapy has a high potential to cause ADRs. Thus, there is a need for vigilant ADR monitoring to prevent morbidity and mortality due to ADRs.

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

Cited by 15 publications

References 39 publications

The Use of Collagen Content as Determined by Spectral Domain Polarization-Sensitive Optical Coherence Tomography to Assess Colon Anastomosis Healing in a Rat Model

The Use of Collagen Content as Determined by Spectral Domain Polarization-Sensitive Optical Coherence Tomography to Assess Colon Anastomosis Healing in a Rat Model

Prospective observational study to evaluate the pattern of adverse drug events in cancer patients receiving anti-cancer agents in a tertiary care hospital

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

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