The importance of peripheral blood leukocytes and macrophage infiltration on bronchial wall wound healing in rats treated preoperatively with anticancer agents

Preoperative chemotherapy is commonly used for small cell lung cancer or advanced non-small cell lung cancer. This study was conducted to investigate the effects of preoperative antineoplastic agents on the postoperative would healing of bronchial anastomoses in a rat model. Cisplatin (CDDP), doxorubicin (ADM), or cyclophosphamide (CPA) was administered either 3 days preoperatively (experiment 1) or 7 days preoperatively (experiment 2). Wound healing was assessed on postoperative days (POD) 3, 5, and 7 after anastomosis of the bronchus, by examining the bursting strength and hydroxyproline tissue content. In experiment 1, significant impairment of wound healing was seen on POD 3 in the CPA-treated rats, but no significant changes were seen in the other groups. Severe leukopenia and marked reduction of macrophage infiltration into the wound were also observed in the CPA-treated rats. The impairment of wound healing coincided with the time of leukopenia and reduced macrophage infiltration into the wounds. In experiment 2, induction chemotherapy did not impair wound healing. Our experimental results suggest that preoperative chemotherapy producing mild leukopenia, or when followed by a sufficient interval to allow for the recovery of myelosuppression, did not impair wound healing of the bronchial anastomoses. The findings of this study also showed that the depletion of macrophages at the anastomotic site is one of the most important causes of impaired wound healing.