The Importance of Peripheral Blood Leukocytes and Macrophage Infiltration on Bronchial Wall Wound Healing in Rats Treated Preoperatively with Anticancer Agents

Abstract

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.

Effects of oxaliplatin and 5-fluorouracil on the healing of colon anastomoses

“…Shirafuji et al suggested that the depletion of macrophages in the anastomotic site is a major cause of impaired wound healing in bronchial anastomosis. 33 This could help explain the decreased bursting pressure in spite of similar collagen levels. We could not fi nd any published study evaluating the effects of OX on collagen synthesis.…”

Granulocyte Macrophage-Colony Stimulating Factor Improves Impaired Anastomotic Wound Healing in Rats Treated with Intraperitoneal Mitomycin-C

“…12,23,25 It seems logical to investigate the possibility of decreasing the anastomotic leakage rate by increasing mononuclear cell accumulation and collagen syntheses in the wound margins. Granulocyte macrophage-colony stimulating factor has been used in the treatment of leukopenia caused by chemotherapy.…”

“…22 The role of macrophages in wound healing is well known and the depletion of macrophages at the anastomotic site is one of the most important causes of impaired wound healing. 23 Macrophages release a number of cytokines and growth factors, which stimulate fibroblast proliferation, and thereby synthesize collagen, and neovascularization. 24 Similarly, in this study, the mean bursting pressure in Group B was significantly lower than that in the control group.…”

Topical autologous serum promotes enucleation wound healing in retinoblastoma patients

“…Some animal studies demonstrated decreased wound tensile strength with a single dose of alkylating agent, whereas other human studies failed to correlate wound healing complications with standard therapeutic doses of chemotherapy. 6,7 In HKEH, a tertiary referral center managing 90% of retinoblastoma patients in Hong Kong, most enucleations are performed after completion of chemoreduction therapy. In our experience, the same chemotherapeutic agents and postoperative regimen have not affected conjunctival wound healing in the absence of perioperative chemotherapy.…”