Radiation therapy attenuates lymphatic vessel repair by reducing VEGFR-3 signalling.

Introduction: Surgery and radiotherapy are key cancer treatments and the leading causes of damage to the lymphatics, a vascular network critical to fluid homeostasis and immunity. The clinical manifestation of this damage constitutes a devastating side-effect of cancer treatment, known as lymphoedema. Lymphoedema is a chronic condition evolving from the accumulation of interstitial fluid due to impaired drainage via the lymphatics and is recognised to contribute significant morbidity to patients who survive their cancer. Nevertheless, the molecular mechanisms underlying the damage inflicted on lymphatic vessels, and particularly the lymphatic endothelial cells (LEC) that constitute them, by these treatment modalities, remain poorly understood. Methods: We used a combination of cell based assays, biochemistry and animal models of lymphatic injury to examine the molecular mechanisms behind LEC injury and the subsequent effects on lymphatic vessels, particularly the role of the VEGF-C/VEGF-D/VEGFR-3 lymphangiogenic signalling pathway, in lymphatic injury underpinning the development of lymphoedema. Results: We demonstrate that radiotherapy selectively impairs key LEC functions needed for new lymphatic vessel growth (lymphangiogenesis). This effect is mediated by attenuation of VEGFR-3 signalling and downstream signalling cascades. VEGFR-3 protein levels were downregulated in LEC that were exposed to radiation, and LEC were therefore selectively less responsive to VEGF-C and VEGF-D. These findings were validated in our animal models of radiation and surgical injury. Discussion: Our data provide mechanistic insight into injury sustained by LEC and lymphatics during surgical and radiotherapy cancer treatments and underscore the need for alternative non-VEGF-C/VEGFR-3-based therapies to treat lymphoedema.

Extensive abdominal surgery and scar does not absolutely contraindicate bilateral flap harvest from the abdomen: A case report.

INTRODUCTION: This case reports a female patient with a history of multiple laparotomies including stoma formations and reversals, who underwent successful bilateral abdominal flap based breast reconstruction. It highlights that even complex and repeated abdominal surgery is not an absolute contraindication to this procedure. PRESENTATION OF CASE: A 52-year-old female with a history of bilateral mastectomy and implant-based breast reconstruction presented with bilateral capsular contracture, wanting removal and alternative breast reconstruction. Her history of ulcerative colitis and multiple complex and extensive abdominal surgeries initially seemed to preclude bilateral abdominal flap harvest and the patient was referred on for another opinion. CT-angiography after the subsequent opinion identified adequate deep inferior epigastric artery perforators and successful bilateral abdomen-based flap reconstruction was performed. DISCUSSION: This is the first case report of successful bilateral abdomen-based flap harvest in a patient with 6 previous laparotomies including stoma formations and reversals. CONCLUSION: Complex and extensive abdominal surgery is not an absolute contraindication to bilateral flap harvest from the abdomen. With accurate CT-angiography to guide pre-operative planning and meticulous surgery, safe flap harvest is possible.