Seroma is a serious fluid collection in a surgical cavity that is clinically evident. Seroma formation is the most common complication after mastectomy and occurs at a rate of 5-52% (mean 30%) under the skin flap or in the dead-space in the axilla [1–3, 6, 11].
Pathogenesis of seroma formation is unclear. Analysis of the seroma that occurred after mastectomy and axillary curettage revealed an exudative fluid including cellular components of acute inflammation . Dead-space after mastectomy is initially filled with a fluid consisting of blood and lymphatic leak. During inflammatory process of surgical trauma, polymorphonuclear leukocytes (PNL) and macrophages migrate to this area due to the effects of histamine, prostaglandin and adenosine in particular, and the vascular ends, which have been closed due to vasoconstriction, open and contribute to the fluid flow. In addition, concentration of soluble particles in the fluid changes with phagocyte infiltration. Osmotic pressure gradient occurs when particle concentration is higher in the seroma than surrounding tissue. Accordingly, it is thought that fluid flow to this area continues until particle concentrations become equal, and thus, seroma persists [13, 14].
Many factors are thought to be associated with seroma formation after mastectomy and axilla dissection. Kuroi et al. investigated evidence level of these factors in a review consisted of 51 randomized, 7 prospective and 7 retrospective studies. They reported that seroma formation was not associated with previous biopsy, type of drainage (closed suction versus static drainage), duration of drainage, number of drains, intensity of negative suction pressure, removal of drains on the fifth postoperative day or when daily drainage volume fell to minimal, immobilization of shoulder, lymph node status or lymph node positivity, number of removed lymph nodes, hormone receptor status, and stage. They also reported moderate level of evidences concerning increased risk for seroma formation in overweight patients, as well as in the patients that underwent modified radical mastectomy as compared to simple mastectomy and in the patients that had higher amount of drainage within the first three days of surgery . We preferred Harada et al. method in our experimental study. This is well documented and frequently used model. Pectoral muscle is excised in this model. There are contraversial thoughts about cautery application, due to its hegative impact on seroma formation. Because of that we tried to abstain from cautery usage. Cautery application in humans differs according to surgeons choice. Some prefers cautery only for the whole procedure. We tried to standardise our experiment and did not use cautery. All the surgeries could have done with the help of coagulation.
Breast surgeries in humans generally needs prophylactic antibiotics. Since these operations are considered as clean, routine application of antibiotics is not mandatory. Also in our experimental study we could have seen infection. Due to its diminished possibility we preferred to abstain from antibiotic usage. There was no infection in animals.
Numerous methods including surgical techniques [6, 15, 16], pressure dressings , immobilization [18, 19], closed drain suction devices [20, 21], sclerosing agents , and various types of tissue adhesives have been investigated in terms of their ability to minimize seroma formation. Nevertheless, these methods are not always effective and may contribute additional morbidity for patients. Although many studies have shown that surgical closure of dead-space is an effective method, it has not been widely accepted since it prolongs surgery by 10 to 20 minutes .
Many studies have shown favorable effects of phenytoin on wound healing. It was reported in those studies that phenytoin reduced inflammation, pain, bacterial contamination and exudate in the wound but augmented fibroblastic proliferation, granulation tissue formation, neo-vascularization and collagenization [9, 10, 23–25]. Depending on favorable effects of phenytoin on wound healing, particularly exudate-reducing effect in the wound, we decided to conduct the present experimental study thinking that phenytoin might have seroma-reducing effect as well. In the present study, the decrease in seroma volume of the phenytoin group was found statistically significant (P = 0.001). Histopathological examination revealed significantly lower angiogenesis and lymphocyte and macrophage infiltration but significantly higher fibrosis. The mechanism of seroma preventing effect of phenytoin is unclear. In the present study, we observed that phenytoin had anti-inflammatory and anti-angiogenic but fibrosis enhancing effects. Seroma-reducing effect of phenytoin might occur from the above-mentioned effects. Excess fluid collection in the surgical trauma area may result from excess wound inflammation in this area. This hypothesis seems to be corroborated by the study of Watt-Boolsen et al., which showed that seroma is a kind of inflammatory exudate and that seroma formation reflects prolongation and severity of inflammatory phase of wound healing . One of the significant findings of the present study is reduced angiogenesis in the phenytoin group. It was shown that vasodilatation is remarkable in the inflammatory phase of wound healing and plays an important role in extravasation of fluid [27, 28]. Prevention of augmentation of angiogenesis and vasodilatation might reduce seroma formation due to decreased fluid flow from capillary bed to dissection area. In their rat model of mastectomy, Kocdor et al. reported that 5 FU might have reduced seroma due to its anti-inflammatory and anti-angiogenetic effects . The other significant finding of the present study is incerasement of fibrosis by phenytoin. Augmented fibrosis in the surgical area might be important in terms of adhesion of flaps to the surgical area and filling of dead-space with fibrosis. In conclusion, local phenytoin application reduces seroma formation in the experimental rat model of mastectomy. Mechanism of seroma-reducing effect of phenytoin and its effect on seroma formation should be illuminated with the future studies. We need to apply different doses of phenytoin and change time of usage.