Delaying Implant-Based Mammary Reconstruction After Radiotherapy Does Not Decrease Capsular Contracture: An In Vitro Study

• Published in: Journal of plastic, reconstructive & aesthetic surgery reconstructive & aesthetic surgery, 2017-09, Vol.70 (9), p.1210-1217
• Main Authors: El-Diwany, Mostafa, MD, MSc, Giot, Jean-Philippe, MD, PhD, Hébert, Marie-Josée, MD, PhD, Danino, Alain M., MD, PhD
• Format: Article
• Language: English
• Subjects: Autophagy; Breast Implants; Breast Neoplasms - radiotherapy; Breast Neoplasms - surgery; Cells, Cultured; Delay; Female; Fibroblasts; Fibrosis; Humans; Implant Capsular Contracture - etiology; Implant Capsular Contracture - prevention & control; Implant-based mammary reconstruction; Mammaplasty; Plastic Surgery; Radiation Injuries - complications; Radiotherapy; Senescence; Time Factors
• ISSN: 1748-6815; 1878-0539
• DOI: 10.1016/j.bjps.2017.06.012

Summary The most common complication of irradiated implant-based mammary reconstruction is fibrosis and capsular contracture. The indications for post mastectomy adjuvant radiotherapy have significantly broadened. Facing an increased number of patients who will require radiotherapy, most guidelines recommend delaying reconstruction after radiotherapy to prevent long-term fibrotic complications. Does radiotherapy permanently alter cellular properties which will adversely affect implant-based reconstruction? If so, is there a benefit in delaying reconstruction after radiotherapy? Our in-vitro model simulates two implant-based mammary reconstruction approaches: the irradiated implant and the delayed implant reconstruction beneath healthy un-irradiated tissue post radiotherapy. We performed cell culture of fibroblasts and endothelial cells, in an attempt to simulate these two surgical conditions. Irradiated fibroblasts simulate the capsular tissue seen around the breast-implant. The delayed reconstruction approach is simulated by non-irradiated fibroblasts conditioned with supernatant culture media obtained from irradiated endothelial cells. Irradiation induced fibrosis through fibroblast differentiation into myofibroblasts, as demonstrated by increased α-smooth-muscle actin levels in fibroblasts. This constitutes the basis for scar tissue contraction observed in irradiated implant-based breast reconstruction. Irradiation of endothelial cells induced irreversible cell cycle arrest known as senescence and secretion of the pro-fibrotic connective tissue growth factor. Non-irradiated fibroblasts conditioned with culture media obtained from irradiated endothelial cells exhibited myofibroblast differentiation and expression of fibrotic phenotype akin to capsular contracture. Our results demonstrate that radiotherapy causes irreversible cellular changes which permanently alter the microenvironment in favour of fibrosis. Given that these changes are permanent, delaying reconstruction does not present an advantage in preventing capsular contracture.