Posterior cranial vault distraction osteogenesis in the immunocompromised patient.

PURPOSE: The treatment of patients with multisuture craniosynostosis is complex and patient-dependent. Cranial distraction osteogenesis is a relatively new procedure for treatment of these patients, with its use increasing in many centers. With this increased use comes an expanding range of indications. Surgical management of multisuture craniosynostosis in therapeutically immunosuppressed patients following a solid organ transplant presents unique challenges. We describe our experience with posterior cranial vault distraction in two patients with multisuture craniosynostosis that had previously undergone organ transplantation. METHODS: Two solid-organ transplant recipient patients with multisuture craniosynostosis were identified. A detailed examination of their medical/transplant history and perioperative details were recorded. RESULTS: The first patient was a 3-year-old girl who received a kidney transplantation in infancy and subsequently presented with a symptomatic Chiari malformation and papilledema. Imaging revealed pansynostosis. She underwent posterior cranial vault distraction extending into a Chiari decompression. Her postoperative course was complicated by distractor site infection at the beginning of consolidation, necessitating early removal of distractors. The second patient was a 2-year-old boy who received a heart transplantation at the age of 3 months and subsequently presented with head shape concerns. Imaging revealed bicoronal and sagittal craniosynostosis. He underwent a posterior cranial vault distraction without complication. Following removal of the distractors, he developed an infection at one of the distractor sites with associated fever and leukocytosis, necessitating washout and drain placement. Both patients achieved successful cranial vault expansion with distraction osteogenesis and at a 2-year follow-up do not have evidence of elevated intracranial pressure. CONCLUSIONS: Immunosuppressive therapy has the potential to inhibit wound healing and place patients at risk for wound infection. Although we have demonstrated successful cranial vault expansion with distraction in two immunosuppressed children, extra care must be taken with these patients when placing semi-buried hardware. Specifically, prompt identification and proactive management of potential infectious complications is critical to applying this technique safely in these patients.

Therapeutic Interventions to Reduce Radiation Induced Dermal Injury in a Murine Model of Tissue Expander Based Breast Reconstruction.

BACKGROUND: Radiation therapy (XRT) induced dermal injury disrupts type I collagen architecture. This impairs cutaneous viscoelasticity, which may contribute to the high rate of complications in expander-based breast reconstruction with adjuvant XRT. The objective of this study was to further elucidate the mechanism of radiation-induced dermal injury and to determine if amifostine (AMF) or deferoxamine (DFO) mitigates type I collagen injury in an irradiated murine model of expander-based breast reconstruction. METHODS: Female Lewis rats (n = 20) were grouped: expander (control), expander-XRT (XRT), expander-XRT-AMF (AMF), and expander-XRT-DFO (DFO). Expanders were surgically placed. All XRT groups received 28 Gy of XRT. The AMF group received AMF 30 minutes before XRT, and the DFO group used a patch for delivery 5 days post-XRT. After a 20-day recovery period, skin was harvested. Atomic force microscopy and Raman spectroscopy were performed to evaluate type I collagen sheet organization and tissue compositional properties, respectively. RESULTS: Type I collagen fibril disorganization was significantly increased in the XRT group compared with the control (83.8% vs 22.4%; P = 0.001). Collagen/matrix ratios were greatly reduced in the XRT group compared with the control group (0.49 ± 0.09 vs 0.66 ± 0.09; P = 0.017). Prophylactic AMF demonstrated a marked reduction in type I collagen fibril disorganization on atomic force microscopy (15.9% vs 83.8%; P = 0.001). In fact, AMF normalized type I collagen organization in irradiated tissues to the level of the nonirradiated control (P = 0.122). Based on Raman spectroscopy, both AMF and DFO demonstrated significant differential protective effects on expanded-irradiated tissues. Collagen/matrix ratios were significantly preserved in the AMF group compared with the XRT group (0.49 ± 0.09 vs 0.69 ± 0.10; P = 0.010). ß-Sheet/α-helix ratios were significantly increased in the DFO group compared with the XRT group (1.76 ± 0.03 vs 1.86 ± 0.06; P = 0.038). CONCLUSIONS: Amifostine resulted in a significant improvement in type I collagen fibril organization and collagen synthesis, whereas DFO mitigated abnormal changes in collagen secondary structure in an irradiated murine model of expander-based breast reconstruction. These therapeutics offer the ability to retain the native microarchitecture of type I collagen after radiation. Amifostine and DFO may offer clinical utility to reduce radiation induced dermal injury, potentially decreasing the high complication rate of expander-based breast reconstruction with adjuvant XRT and improving surgical outcomes.

Nonvascularized Bone Graft Reconstruction of the Irradiated Murine Mandible: An Analogue of Clinical Head and Neck Cancer Treatment.

Nonvascularized bone grafts (NBGs) represent a practical method of mandibular reconstruction that is precluded in head and neck cancer patients by the destructive effects of radiotherapy. Advances in tissue-engineering may restore NBGs as a viable surgical technique, but expeditious translation demands a small-animal model that approximates clinical practice. This study establishes a murine model of irradiated mandibular reconstruction using a segmental iliac crest NBG for the investigation of imperative bone healing strategies. Twenty-seven male isogenic Lewis rats were divided into 2 groups; control bone graft and irradiated bone graft (XBG). Additional Lewis rats served as graft donors. The XBG group was administered a fractionated dose of 35Gy. All rats underwent reconstruction of a segmental, critical-sized defect of the left hemi-mandible with a 5 mm NBG from the iliac crest, secured by a custom radiolucent plate. Following a 60-day recovery period, hemi-mandibles were evaluated for bony union, bone mineralization, and biomechanical strength (P < 0.05). Bony union rates were significantly reduced in the XBG group (42%) compared with controls (80%). Mandibles in the XBG group further demonstrated substantial radiation injury through significant reductions in all metrics of bone mineralization and biomechanical strength. These observations are consistent with the clinical sequelae of radiotherapy that limit NBGs to nonirradiated patients. This investigation provides a clinically relevant, quantitative model in which innovations in tissue engineering may be evaluated in the setting of radiotherapy to ultimately provide the advantages of NBGs to head and neck cancer patients and reconstructive surgeons.

Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model.

BACKGROUND: Breast cancer is most commonly managed with a combination of tumor ablation, radiation, and/or chemotherapy. Despite the oncologic benefit of these treatments, the detrimental effect of radiation on surrounding tissue challenges the attainment of ideal breast reconstruction outcomes. The purpose of this study was to determine the ability of topical deferoxamine (DFO) to reduce cutaneous ulceration and collagen disorganization following radiotherapy in a murine model of expander-based breast reconstruction. METHODS: Female Sprague-Dawley rats (n = 15) were divided into 3 groups: control (expander), XRT (expander + radiation), and DFO (expander + radiation + deferoxamine [DFO]). Expanders were placed in a submusculocutaneous plane in the right upper back and ultimately filled to 15 mL. Radiation was administered via a fractionated dose of 28 Gy. Deferoxamine was delivered topically for 10 days following radiation. After a 20-day recovery period, skin ulceration and dermal type I collagen organization were analyzed. RESULTS: Compared with control, the XRT group demonstrated a significant increase in skin ulceration (3.7% vs 43.3%, P = 0.00) and collagen fibril disorganization (26.3% vs 81.8%, P = 0.00). Compared with the XRT group, treatment with topical DFO resulted in a significant reduction in ulceration (43.3% vs 7.0%, P = 0.00) and fibril disorganization (81.8% vs 15.3%, P = 0.00). There were no statistical differences between the control and DFO groups in skin ulceration or collagen disorganization. CONCLUSIONS: This study suggests topical DFO is capable of reducing skin ulceration and type I collagen fibril disorganization following radiotherapy. This novel application of DFO has potential to enhance expander-based breast reconstruction outcomes and improve quality of life for women suffering the devastating effects of breast cancer.