Harvey Chim

New frontiers in calvarial reconstruction : integrating computer-assisted design and tissue engineering in cranioplasty

Summary: Repair of large and complex calvarial defects remains a particular challenge for reconstruction. The paucity of techniques and materials emphasizes the need for alternative bone formation strategies. Recent integrative approaches suggest that successful reconstruction requires interdisciplinary teams, with surgeons interacting with imaging experts, materials scientists, and engineers. In this review, the authors present an overview of current materials used in calvarial reconstruction. Subsequently, progress in computer-designed prostheses, tissue engineering, and osteoinduction strategies is discussed. Finally, the authors discuss their experience with the integration of computer-aided fabrication of customized implants and tissue engineering for calvarial reconstruction.

Propranolol induces regression of hemangioma cells through HIF-1α-mediated inhibition of VEGF-A

Objective: To investigate the mechanism of propranolol on regression of infantile hemangiomas. Background: Propranolol has been found to be effective in treatment of severe hemangiomas of infancy. However, its mechanism of action is as yet unknown. Methods: Cultured proliferating and involuting hemangioma endothelial cells were treated with varying concentrations of propranolol for up to 4 days. Analysis was performed using cell viability, migration, and tubulogenesis assays, as well as quantitative RT-PCR and flow cytometry. Western blots and ELISA assays were used to assess protein expression. Results: Treatment with propranolol led to a dose dependent cytotoxic effect in hemangioma endothelial cells with decreased cell viability, migration, and tubulogenesis. This cytotoxic effect was VEGF (vascular endothelial growth factor) dependent, as demonstrated by decreased VEGF, VEGF-R1, and VEGF-R2 production. Decreased signaling through the VEGF pathway resulted in downregulation of PI3/Akt and p38/MAPK activity. Decreased VEGF activity was mediated through the hypoxia inducible factor (HIF)-1&agr; pathway but not through NF-&kgr;&bgr; signaling. Conclusions: Collectively, these data suggest that propranolol exerts its suppressive effects on hemangiomas through the HIF-1&agr;-VEGF-A angiogenesis axis, with effects mediated through the PI3/Akt and p38/MAPK pathways. These findings provide a plausible mechanism of action of propranolol on regression of infantile hemangiomas.

Reconstruction of Mandibular Defects

Defects requiring reconstruction in the mandible are commonly encountered and may result from resection of benign or malignant lesions, trauma, or osteoradionecrosis. Mandibular defects can be classified according to location and extent, as well as involvement of mucosa, skin, and tongue. Vascularized bone flaps, in general, provide the best functional and aesthetic outcome, with the fibula flap remaining the gold standard for mandible reconstruction. In this review, we discuss classification and approach to reconstruction of mandibular defects. We also elaborate upon four commonly used free osteocutaneous flaps, inclusive of fibula, iliac crest, scapula, and radial forearm. Finally, we discuss indications and use of osseointegrated implants as well as recent advances in mandibular reconstruction.

Outcome comparison of endoscopic and transpalpebral decompression for treatment of frontal migraine headaches.

Background: This study was designed to compare the efficacy of the transpalpebral versus endoscopic approach to decompression of the supraorbital and supratrochlear nerves in patients with frontal migraine headaches. Methods: The medical charts of 253 patients who underwent surgery for frontal migraine headaches were reviewed. These patients underwent either transpalpebral nerve decompression (n = 62) or endoscopic nerve decompression (n = 191). Preoperative and 12-month or greater postoperative migraine frequency, duration, and intensity were analyzed to determine the success of the surgeries. Results: Forty-nine of 62 patients (79 percent) in the transpalpebral nerve decompression group and 170 of 191 patients (89 percent) who underwent endoscopic nerve decompression experienced a successful outcome (at least a 50 percent decrease in migraine frequency, duration, or intensity) after 1 year from surgery. Endoscopic nerve decompression had a significantly higher success rate than transpalpebral nerve decompression (p < 0.05). Thirty-two patients (52 percent) in the transpalpebral nerve decompression group and 128 patients (67 percent) who underwent endoscopic nerve decompression observed elimination of migraine headaches. The elimination rate was significantly higher in the endoscopic nerve decompression group than in the transpalpebral nerve decompression group (p < 0.03). Conclusion: Endoscopic nerve decompression was found to be more successful at reducing or eliminating frontal migraine headaches than transpalpebral nerve decompression and should be selected as the first choice whenever it is anatomically feasible. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The auriculotemporal nerve in etiology of migraine headaches: Compression points and anatomical variations

Background: The auriculotemporal nerve has been identified as one of the peripheral trigger sites for migraine headaches. However, its distal course is poorly mapped following emergence from the parotid gland. In addition, a reliable anatomical landmark for locating the potential compression points along the course of the nerve during surgery has not been sufficiently described. Methods: Twenty hemifaces on 10 fresh cadavers were dissected to trace the course of the auriculotemporal nerve from the inferior border of the zygomatic arch to its termination in the temporal scalp. The compression points were mapped and the distances were measured from the most anterosuperior point of the external auditory meatus, which was used as a fixed anatomical landmark. Results: Three potential compression points along the course of the auriculotemporal nerve were identified. Compression points 1 and 2 corresponded to preauricular fascial bands. Compression point 1 was centered 13.1 ± 5.9 mm anterior and 5.0 ± 7.0 mm superior to the most anterosuperior point of the external auditory meatus, whereas compression point 2 was centered at 11.9 ± 6.0 mm anterior and 17.2 ± 10.4 mm superior to the most anterosuperior point of the external auditory meatus. A significant relationship was found between the auriculotemporal nerve and superficial temporal artery (compression point 3) in 80 percent of hemifaces, with three patterns of interaction: a single site of artery crossing over the nerve (62.5 percent), a helical intertwining relationship (18.8 percent), and nerve crossing over the artery (18.8 percent). Conclusion: Findings from this cadaver study provide information relevant to the operative localization of potential compression points along the auriculotemporal nerve.

Three-dimensional preoperative virtual planning and template use for surgical correction of craniosynostosis.

BACKGROUND Surgical correction of craniosynostosis aims to remodel the cranial vault to achieve a morphology approaching that of age-matched norms. However, current surgical technique is highly subjective and based largely on the surgeons artistic vision in creating a normal head shape. Here, we present our technique and report our experience with the use of virtual surgery using computer-assisted design (CAD)/computer-assisted manufacturing (CAM) techniques to create a prefabricated template for the planning of osteotomies and the placement of bone segments, to achieve standardised, objective and precise correction of craniosynostosis. METHODS Four patients who underwent cranial vault remodelling (CVR; three metopic synostosis and one sagittal synostosis) underwent virtual surgical planning (VSP) preoperatively using CAD/CAM techniques. VSP allows pre-planning of osteotomies to achieve the desired cranial vault shape. Surgical osteotomies and placement of bone segments were performed intra-operatively based on prefabricated templates. RESULTS All patients demonstrated markedly improved head shape postoperatively. One patient developed a subdural haematoma 6 weeks postoperatively subsequent to a fall where he hit his head. The haematoma was drained and a soft spot was present in that location 3 months postoperatively. CONCLUSION The use of virtual surgery and prefabricated cutting guides allows for a more precise and rapid reconstruction. Surgical osteotomies are pre-planned and rapidly performed using a template, and precise placement of calvarial bone segments is achieved without the need for subjective assessment of the desired calvarial shape. In addition, patients and families have a significantly better understanding of the disease process and anticipated surgery preoperatively with the visualisation achieved through virtual surgery. This results in better alignment of hopes and expectations between the parents and surgeons.

Application-specific selection of biomaterials for pediatric craniofacial reconstruction: developing a rational approach to guide clinical use.

Background: Biomaterials provide an invaluable alternative to autogenous bone graft for pediatric craniofacial reconstruction. However, there is no uniform agreement on the choice of biomaterial for different reconstructive needs. Methods: Patients who had reconstruction of the craniofacial skeleton with alloplastic materials from 1994 to 2006 by a single surgeon were reviewed. Biomaterials used consisted of three classes: cement pastes, biomaterials designed to be replaced by bone, and prefabricated polymers. The study included 25 patients with a mean age of 5.5 years and a mean follow-up of 3.3 years. Results: Cement pastes used for onlay augmentation to the cranial skeleton in eight patients consisted of hydroxyapatite (n = 5) and calcium phosphate (n = 3). One patient had a postoperative infection that resolved with partial implant removal and antibiotics. Biomaterials designed to be replaced by bone consisted of bioactive glass (n = 3) and demineralized bone (n = 8), which were used for inlay reconstruction of full-thickness calvarial defects in 11 patients. Computed tomographic scanning showed adequate bone mineralization in nine patients; two of the three patients with calvarial defects greater than 5 cm in diameter demonstrated variable mineralization. Prefabricated porous polyethylene was used in six patients for either onlay malar augmentation (n = 3) or inlay calvarial reconstruction (n = 3). One patient had a peri-implant infection that resolved with aspiration, irrigation, and intravenous antibiotics. Conclusions: The authors developed an algorithm to guide use of biomaterials in craniofacial reconstruction based on whether (1) growth of the underlying craniofacial skeleton is nearly complete (>90 percent); (2) onlay or inlay reconstruction is to be performed; and (3) the reconstruction is performed in a load-bearing or non-load-bearing area.

History of the Kleeblattschädel deformity: Origin of concepts and evolution of management in the past 50 years

The history and evolution of surgical strategies for the treatment of Kleeblattschädel deformity are not well described in the medical literature. Kleeblattschädel anomaly is one of the most formidable of the craniosynostoses, requiring a multidisciplinary team for surgical treatment. The initial descriptions of this cloverleaf deformity and the evolution of surgical treatment are detailed in the present report. Two illustrative cases of Kleeblattschädel deformity, syndromic and nonsyndromic craniosynostoses treated by the senior authors, are also described along with insights into operative strategies.

Optimizing the use of local muscle flaps for knee megaprosthesis coverage.

Primary muscle flap cover of megaprostheses following limb salvage surgery for tumors around the knee serves to decrease infection rates, provide additional soft tissue cover over the implant, and act as a bed for split-skin grafting. The purpose of this study is to demonstrate the role of supplementary muscle flaps such as the hemisoleus, gracilis, and semimembranosus in augmenting coverage provided by gastrocnemius muscle flaps. Between August 1999 and August 2006, 10 patients underwent resection of distal femur (n = 5) or proximal tibia (n = 5) sarcomas, followed by bone reconstruction with a modular megaprosthesis and soft tissue coverage with local pedicled flaps. The average age was 31 years (range, 13 to 47), with pathologic diagnoses inclusive of osteosarcoma (n = 7), chondrosarcoma (n = 2), and recurrent giant cell tumor (n = 1). For proximal tibial tumors, both bellies of the gastrocnemius with hemisoleus for additional soft tissue cover were used. For distal femoral tumors, 1 gastrocnemius belly sutured to the extensor mechanism and gracilis or semimembranosus provided adequate soft tissue cover. All flaps survived without complications, all wounds healed well, and all patients were ambulant after surgery. The role of supplementary muscle flaps was demonstrated in specific situations, where coverage of the subcutaneous area of the midtibia was deficient and where a significant amount of the vastus medialis or gastrocnemius has been resected. Technical refinements included primary skin grafting to relieve tension during skin closure and excision of the aponeurosis over the gastrocnemius and hemisoleus to increase the reach and surface area of the muscle flap.

Human circulating peripheral blood mononuclear cells for calvarial bone tissue engineering.

Background: Large-scale production of engineered tissues requires an adequate source of expandable cells. Current strategies that involve harvesting of cells from donor tissue or bone marrow for tissue engineering are invasive and unfeasible for obtaining large quantities of cells in a clinical setting. Peripheral blood has been reported to contain circulating hematopoietic cells as well as, in significantly smaller quantities, mesenchymal cells Methods: An adherent subset of CD14+ mononuclear cells was isolated from human peripheral venous blood and characterized in vitro by light microscopy, immunohistochemistry, flow cytometry, and quantitative differentiation assays. These cells were then evaluated for the purposes of tissue engineering in a rat calvarial defect model, in combination with biodegradable polymer matrices made from poly-e-caprolactone. Specimens were analyzed 6 weeks after implantation with histologic analysis, microcomputed tomography, and HLA immunostaining. Results: CD14+ mononuclear cells were induced to differentiate into osteoblast-like cells in vitro, with areas of mineralization. In a rat calvarial defect model, tissue-engineered bone with evidence of mineralization was formed within 6 weeks. HLA immunohistochemistry demonstrated that de novo bone formation originated from the transplanted human cells. Conclusions: These findings show, for the first time, to our knowledge, the derivation of bone from human blood. They also demonstrate the utility of circulating mononuclear cells as a minimally invasive, potentially unlimited pool of cells for tissue engineering and organ regeneration.