Examination of the Effects of Celecoxib on Postmastectomy Seroma and Wound Healing

Objectives: To examine the effect of celecoxib on wound healing and development of seroma after mastectomy.
Seroma is an accumulation of serous fluid in dead space emerging after breast cancer surgery. The pathophysiology of seroma has not been clearly elucidated. Development of seroma leads to prolongation of hospital stay, increase in costs, ischemia of the flaps, infections due to fluid accumulation, and delayed adjuvant treatment.
Seroma is still a current problem, and the most common treatment method for this problem is drainage and repeated aspirations for 5–7 days after surgery.
Methods: The effect of celecoxib whose anti-inflammatory, antiangiogenic, and antioxidant effectiveness has been demonstrated in a mastectomy model applied on female Wistar rats has been investigated in the present study. A total of 20 rats including 10 rats in the control and 10 in the celecoxib group were studied.
Intraperitoneal 0.25 cc/250 g (20 mg/kg/day) celecoxib was administered to the celecoxib group for 5 days after mastectomy, and the same volume of physiological saline solution was given to the control group for 5 days. Rats were followed up for 10 days after surgery. During this process, vitality of the rats, movements of the extremities, wound healing conditions, wound infections, flap necrosis, and occurrence of seroma were recorded. At the end of this period, seromas were aspirated, tissue samples were retrieved, and the rats were sacrificed. Fibrin, hemorrhage, edema, vascularization, congestion, polymorphonuclear leukocytes, and increase in fibrotic tissue fibroblasts, lymphocytes, and macrophages were evaluated in tissue samples.
In seroma fluids, interleukin-1 beta (IL-1β), an acute phase reactant, and vascular endothelial growth factor, a vital parameter of vascular proliferation and angiogenesis, were examined.
Results: At the end of the experiments, the seroma volume decreased significantly in the celecoxib group (p=0.804; 0.001), the IL-1β level decreased significantly as detected in the biochemical examination (p=0.014), and in the histopathological examination, an increase in congestion in the celecoxib group was determined.
Conclusion: In conclusion, celecoxib markedly decreased interleukin and the volume of seroma after mastectomy; suppressed the level of an acute phase reactant, IL-1β; and demonstrated this effect through its anti-inflammatory activity. We believe that the effects of celecoxib should be investigated using different dose applications and larger number of subjects.

Celecoxib’in mastektomi sonrasýnda geliþen seroma ve yara iyileþmesine etkisinin incelenmesi

Amaç:
Seroma meme kanser cerrahisi sonrasýnda ortaya çýkan ölü boþlukta seröz sývý birikimidir. Seromanýn patofizyolojisi net olarak aydýnlatýlamamýþtýr. Seroma geliþimi hastanede kalýþ süresinin uzamasý, maliyet artýþý, fleplerde iskemi, sývý birikimine baðlý infeksiyon ve adjuvan tedavide gecikmeye yol açmaktadýr. Seroma günümüzde halen güncel bir sorundur ve bu sorun için en çok uygulanan yöntem ameliyat sonrasý beþ - yedi gün süre ile drenaj ve tekrarlanan aspirasyonlardan ibarettir.
Gereç ve Yöntemler:
Bu çalýþmada antiinflamatuar, antianjiyogenik ve antioksidan etkinliði gösterilmiþ olan celecoxib’in diþi Wistar ratlar üzerinde uygulanan mastektomi modelinde seroma’ya etkinliði incelendi. Kontrol grubunda 10, celecoxib grubunda 10 olmak üzere toplam 20 rat incelemeye alýndý. Mastektomi sonrasýnda celecoxib grubuna intraperitoneal 0,25 cc/250gr (20 mg/kg/gün) celecoxib beþ gün süre ile, kontrol grubuna ise ayný volümde serum fizyolojik beþ gün süre ile verildi. Ratlar ameliyat sonrasýnda 10 gün izlendi. Bu süreç içinde ratlarýn canlýlýklarý, kol hareketleri, yara yeri iyileþme durumlarý, yara infeksiyonu, flep nekrozu ve seroma oluþumlarý kaydedildi. Bu süre sonunda seromalar aspire edildi ve doku örnekleri alýnarak ratlar sakrifiye edildi. Doku örneklerinde fibrin, kanama, ödem, damarlanma, konjesyon, polimorf nüveli lökositler, fibröz doku artýþý, fibroblast, lenfosit ve makrofajlar deðerlendirildi. Seroma sývýlarýnda ise inflamasyon parametrelerinden akut faz reaktaný olan interlökin 1 beta ve damar proliferasyonu ve anjiyogenezin temel parametresi olan vasküler endotelyal büyüme faktörü incelemesi yapýldý.
Bulgular:
Deneyler sonunda biyokimyasal incelemede celecoxib uygulanan grupta seroma hacimlerinin belirgin olarak azaldýðý (p≤0,001), seroma sývýsýnda interlökin 1 beta düzeyinin belirgin olarak azaldýðý (p=0,014), histopatolojik incelemede ise celecoxib grubunda konjesyonun arttýðý (p=0,044) tesbit edildi.

Sonuçlar:
Bu çalýþmanýn sonucunda, celecoxib’in mastektomi sonrasý seroma hacimlerini belirgin olarak azalttýðý, bir akut faz reaktaný olan interlökin 1 betayý baskýladýðý; bu etkisinin antiinflamatuar etkisi ile olduðu sonucuna varýldý. Celecoxib’in etkilerinin farklý doz uygulamalarýyla ve daha geniþ sayýda denek üzerinde araþtýrýlmasý gerektiði düþünüldü.