Efficacy of hyperbaric oxygen after microtia reconstruction using costal cartilage: A retrospective case-control study.

Introduction: Microtia reconstruction with autologous costal cartilage framework grafting is challenging because the three-dimensional structure of the ear is highly complex, and meeting the high aesthetic demands of patients can be difficult. If the skin flap overlying the framework is thinned to achieve a smooth and accentuated outline, a poor blood supply in the thin skin flap may lead to skin necrosis, exposure of the framework, and poor surgical results. Hyperbaric oxygen (HBO2) therapy can promote the healing of complex wounds and flaps. This study sought to determine the effectiveness of HBO2 therapy for the prevention of postoperative complications after framework grafting in microtia reconstruction. Methods: We retrospectively evaluated postoperative complications and compared outcomes in pediatric patients who underwent costal cartilage grafting for microtia reconstruction at our institution between 2011 and 2015, according to whether or not they received postoperative HBO2 therapy. HBO2 therapy was applied once daily for a total of 10 sessions starting on the first postoperative day. Results: During the study period, eight patients received HBO2 therapy after costal cartilage grafting, and 12 did not. There was no significant difference in the incidence of postoperative ulcers. However, the incidence of framework exposure was lower, and the healing time was shorter in patients who received HBO2 therapy than in those who did not. Discussion: HBO2 therapy can be used safely in pediatric patients to reduce postoperative complications and improve the aesthetic outcome of microtia reconstruction. After costal cartilage grafting, HBO2 therapy should be considered as adjuvant therapy.

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation.

Epidermal growth factor receptor (EGFR) overexpression and EGFR-mediated signaling pathway dysregulation have been observed in tumors from patients with various cancers, especially non-small cell lung cancer. Thus, several anti-EGFR drugs have been developed for cancer therapy. For patients with known EGFR activating mutations (EGFR exon 19 in-frame deletions and exon 21 L858R substitution), treatment with an EGFR tyrosine kinase inhibitor (EGFR TKI; gefitinib, erlotinib or afatinib) represents standard first-line therapy. However, the clinical efficacy of these TKIs is ultimately limited by the development of acquired drug resistance such as by mutation of the gatekeeper T790 residue (T790M). To overcome this acquired drug resistance and develop novel anti-EGFR drugs, a cell-based assay system for EGFR TKI resistance mutant-selective inhibitors is required. We constructed a novel cell-based assay for the evaluation of EGFR TKI efficacy against EGFR mutation. To this end, we established non-tumorigenic immortalized breast epithelial cells that proliferate dependent on EGF (MCF 10A cells), which stably overexpress mutant EGFR. We found that the cells expressing EGFR containing the T790M mutation showed higher resistance against gefitinib, erlotinib and afatinib compared with cells expressing wild-type EGFR. In contrast, L858R mutant-expressing cells exhibited higher TKI sensitivity. The effect of T790M-selective inhibitors (osimertinib and rociletinib) on T790M mutant-expressing cells was significantly higher than gefitinib and erlotinib. Finally, when compared with commercially available isogenic MCF 10A cell lines carrying introduced mutations in EGFR, our EGFR mutant-overexpressing cells exhibited obviously higher responsiveness to EGFR TKIs depending on the underlying mutations because of the higher levels of EGFR phosphorylation in the EGFR mutant-overexpressing cells than in the isogenic cell lines. In conclusion, we successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation.