The Effects of Intraperitoneal 5-Fluorouracil Use at Different Doses on the Recovery Time of Experimental Intestinal Anastomoses

Abstract

Aim: The most important complication of colorectal surgery is the separation of anastomosis or leakage. It is known that many local and systemic factors are effective in the healing process of colon anastomoses and in the formation of anastomotic leaks. One of these factors is chemotherapy. In order to achieve successful results in gastrointestinal system cancers, it is necessary to find the sensitive balance between the surgical method and chemotherapy and radiotherapy. 

Method: In our study, intraperitoneal administration of the most commonly used cytostatic 5-Fluorouracil (5-FU) in gastrointestinal tract cancers was investigated. For this purpose, 42 female Wistar Albino rats were divided into three main groups, each containing an equal number of subjects. Groups are Control group (Intraperitoneal NaCl), single dose 5-Fluorouracil group (Intraperitoneal 20 mg/kg/day 5-FU) and multiple dose 5-Fluorouracil group (Intraperitoneal 20 mg/kg/day 5-FU 3 days consecutively). Half of the 14 subjects in each main group were sacrificed on the 3rd day and the other half on the 7th day. Leukocyte and Albümin values were investigated for the purpose of examining the side effects of 5-FU. Bursting pressure, hydroxyproline level and histopathologic parameters were used to assess the differences in anastomotic healing between groups.

Results: There was no statistically significant difference in comparison with the control group of the chemotherapeutic 5-FU application in terms of intra-abdominal adhesions after surgical intervention (p>0,05). Albümin and leukocyte values; According to the control groups, statistically significant low results were obtained in groups used in 5-FU (p<0,05). Bursting pressure, histopathologic examination results in the evaluation of anastomotic healing; Multiple doses of 5-FU showed statistically significant low scores in groups with a single dose of 5-FU and control groups (p<0,05).

Conclusion: The impression obtained from the study showed that the high dose intraperitoneal 5-FU treatment, which was started in the early postoperative period, had a negative effect by delaying the anastomotic healing, but in limited doses Intraperitoneal 5-FU does not show any negative effects on anastomotic healing and is in parallel with control groups. In the light of this data from our experimental work; In clinical practice, it can be said that the chemotherapy, which has been feared and started late, may also find the usage area in the early postoperative period in limited doses.

Keywords

• 5-Fluorouracil
• anastomosis
• regional perfusion cancer chemotherapy

Farklı Dozlarda Intraperitoneal 5-Fluorouracil Kullanımının Deneysel Intestinal Anastomozların İyileşme Süresi Üzerine Etkileri

Abstract

Amaç: Kolorektal cerrahinin en önemli komplikasyonu anastomoz ayrılması veya kaçaktır. Lokal ve sistemik pek çok faktörün kolon anastomozlarının iyileşme sürecinde ve anastomoz kaçaklarının oluşmasında etkili olduğu bilinmektedir. Bu faktörlerden bir tanesi de kemoterapidir. Gastrointestinal sistem kanserlerinde başarılı sonuçlar alabilmek için cerrahi yöntem ile kemoterapi ve radyoterapi arasındaki hassas dengeyi bulabilmek şarttır.

Yöntem: Çalışmada gastrointestinal sistem (GİS) kanserlerinde en çok kullanılan sitostatik 5-Fluorouracil (5-FU) intraperitoneal uygulanması araştırılmıştır. Bu amaçla 42 adet Wistar Albino cinsi dişi sıçan her biri eşit sayıda denek içeren kontrol grubu (Intraperitoneal NaCl), tek doz 5-Fluorouracil grubu (Intraperitoneal 20 mg/kg/gün 5-FU) ve multipl doz 5-Fluorouracil grubu (Intraperitoneal 20 mg/kg/gün 5-FU 3 gün art arda) olmak üzere üç ana gruba ayrılmıştır. Her ana gruptaki 14 deneğin yarısı 3. günde, diğer yarısı ise 7. günde sakrifiye edilerek alt gruplar elde edilmiştir. 5-FU'in yan etkilerini incelemek amacıyla lökosit ve albümin değerleri araştırılmıştır. Anastomoz iyileşmesinin gruplar arasındaki farklılıklarını değerlendirmek için ise patlama basıncı, hidroksiprolin düzeyi ve histopatolojik parametreler kullanılmıştır.

Bulgular: Cerrahi girişim sonrası batın içi yapışıklıklar açısından 5-FU uygulamasının kontrol grubu ile karşılaştırılmasında istatistiksel açıdan anlamlı fark bulunmadı (p> 0,05). Albümin ve lökosit değerlerinde; kontrol gruplarına göre 5-FU kullanılan gruplarda istatistiksel olarak anlamlı düşük sonuçlar elde edildi (p<0,05). Anastomoz iyileşmesinin değerlendirilmesinde patlama basıncı, histopatolojik inceleme sonuçları multipl doz 5-FU kullanılan gruplarda tek doz 5-FU ve kontrol gruplarına göre istatistiksel olarak anlamlı düşük skorlar gösterdi (p<0,05).

Sonuç: Erken postoperatif dönemde başlanan multipl olarak verilen yüksek doz intraperitoneal 5-FU tedavisinin anastomoz iyileşmesini geciktirerek negatif etki gösterdiği, buna karşın sınırlı dozlarda uygulanan intraperitoneal 5-FU'in anastomoz iyileşmesi üzerinde hiçbir negatif etki göstermeyip kontrol grupları ile paralel iyileşme gösterdiği yönündedir. Deneysel çalışmadan elde edilen bu veriler ışığında; klinik uygulamada şimdiye kadar korkulan ve geç başlanan kemoterapinin, sınırlı dozlarda erken postoperatif dönemde de kullanım alanı bulabileceği söylenebilir.

Keywords

• 5-Florourasil
• anastomoz
• bölgesel perfüzyon kanser kemoterapisi

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