Faculty Bibliography

ABSTRACT: Because of increased risk for nipple necrosis, many surgeons believe large ptotic breasts to be a relative contraindication to nipple-sparing mastectomy (NSM). A retrospective review was performed on 85 consecutive patients who underwent NSM with 141 immediate perforator free-flap breast reconstructions. We analyzed the subset of patients with large ptotic breasts, defined as cup size C or greater, sternal notch to nipple distance greater than 24 cm and grade 2 or 3 breast ptosis. Of the 85 patients, 19 fit the inclusion criteria. Breast cup size ranged from 34C to 38DDD. There was 1 case of nipple necrosis in the patient with previous breast radiation (5%), 1 hematoma (5%), and no flap losses. Five (26%) patients underwent subsequent mastopexy or breast reduction, a mean of 6.6 months after the primary procedure. We demonstrate that NSM and free-flap breast reconstruction can be safely and reliably performed in selected patients.

A serious consequence of diabetes mellitus is impaired wound healing, which largely resists treatment. We previously reported that topical application of calreticulin (CRT), an endoplasmic reticulum chaperone protein, markedly enhanced the rate and quality of wound healing in an experimental porcine model of cutaneous repair. Consistent with these in vivo effects, in vitro CRT induced the migration and proliferation of normal human cells critical to the wound healing process. These functions are particularly deficient in poor healing diabetic wounds. Using a genetically engineered diabetic mouse (db/db) in a full-thickness excisional wound healing model, we now show that topical application of CRT induces a statistically significant decrease in the time to complete wound closure compared with untreated wounds by 5.6 days (17.6 vs. 23.2). Quantitative analysis of the wounds shows that CRT increases the rate of reepithelialization at days 7 and 10 and increases the amount of granulation tissue at day 7 persisting to day 14. Furthermore, CRT treatment induces the regrowth of pigmented hair follicles observed on day 28. In vitro, fibroblasts isolated from diabetic compared with wild-type mouse skin and human fibroblasts cultured under hyperglycemic compared with normal glucose conditions proliferate and strongly migrate in response to CRT compared with untreated controls. The in vitro effects of CRT on these functions are consistent with CRT's potent effects on wound healing in the diabetic mouse. These studies implicate CRT as a potential powerful topical therapeutic agent for the treatment of diabetic and other chronic wounds.

INTRODUCTION: Beginning in 2004, we modified our surgical technique for a cranial vault remodeling in sagittal and lambdoid synostosis. Beginning in the early 1990s, we started using a calvarial vault remodeling technique in sagittal and lambdoid synostosis that involves removing the posterior two thirds of the skull, extending from the coronal suture to below the lambdoid suture to within 1-1.5 cm of the foramen magnum. Up until 2004, the bone fixation evolved from wire fixation, then micro-metallic fixation plates and resorbable sutures. DISCUSSION: Over the last 9 years, we have used a novel technique of absorbable fixation plates and a polydioxanone suture trellis or lattice network, which has reduced operating times significantly and continued to give excellent results. Additional advantages include the absence of a need for molding or protective helmets, the absence of bony defects at the completion of the procedure, the absence of age limitation, and the ability to correct the tightly constricted occiput. CONCLUSION: To date, we have had no significant complications, no return to operating room, and the aesthetics have held up well since its introduction.

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. METHODS: Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3.0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732. FINDINGS: 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6.0%) and 62 who had carotid endarterectomy (6.3%) had restenosis or occlusion (hazard ratio [HR] 0.90, 95% CI 0.63-1.29; p=0.58). Female sex (1.79, 1.25-2.56), diabetes (2.31, 1.61-3.31), and dyslipidaemia (2.07, 1.01-4.26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2.26, 1.34-3.77) but not after carotid artery stenting (0.77, 0.41-1.42). INTERPRETATION: Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation. FUNDING: National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.

BACKGROUND: : Lipoaspirate centrifugation creates graded density of adipose tissue. High-density fat contains more vasculogenic cytokines and progenitor cells and has greater graft survival than low-density fat. The authors hypothesize that accelerating the bone marrow-derived progenitor cell response to injected low-density fat will improve its graft survival. METHODS: : Male 8-week-old FVB mice (n = 60) were grafted with either high-density (n = 20) or low-density (n = 40) human lipoaspirate. Half of the mice receiving low-density fat (n = 20) were treated with a stem cell mobilizer for 14 days. Grafted fat was harvested at 2 and 10 weeks for analysis. RESULTS: : Low-density fat, low-density fat plus daily AMD3100, and high-density fat had 26 +/- 3.0, 61.2 +/- 7.5, and 49.6 +/- 3.5 percent graft survival, respectively, at 2 weeks (low-density fat versus low-density fat plus daily AMD3100 and low-density fat versus high-density fat, both p < 0.01). Similar results were observed 10 weeks after grafting. Mice receiving low-density fat plus daily AMD3100 had significantly more vasculogenic progenitor cells per cubic centimeter of peripheral blood (p < 0.01) and more new blood vessels (p < 0.01). Both low-density fat plus daily AMD3100 and high-density fat contained more stromal-derived factor-1alpha and vascular endothelial growth factor mRNA/protein. CONCLUSION: : Endogenous progenitor cell mobilization enhances low-density fat neovascularization, increases vasculogenic cytokine expression, and improves graft survival to a level equal to that of high-density fat grafts.

BACKGROUND: Larger thoracic defects require stable yet flexible reconstruction to prevent flail chest and debilitating respiratory impairment. We present the use of locking rib-spanning plates as a chest salvage procedure. METHODS: A 30-year-old male presented with a massive desmoid tumor in the posterolateral aspect of the chest wall. The mass measured 22 by 14 by 6 cm and involved the posterior third through seventh ribs. The patient underwent wide excision and reconstruction in layers with a porcine dermal substitute for the pleura, locking rib-spanning plates for structural support, and coverage with ipsilateral latissimus dorsi. RESULTS: The patient tolerated the procedure without complication. He was extubated on postoperative day zero and has had an uneventful course. CONCLUSION: Chest wall reconstruction with rib-spanning plates is an alternative method of reconstruction for large chest wall defects. This method limits the foreign body burden while providing rigid structural support. This technique also makes chest wall reconstruction possible in situations that might previously have been treated with pneumonectomy.

Approximately half of head and neck carcinomas arise from the oral cavity. Imaging plays an essential role in the preoperative evaluation of oral cavity carcinomas. MR imaging is particularly advantageous in the evaluation of the oral cavity, with better depiction of the anatomy in this region and reduction of dental artifacts compared with CT. MR is also the preferred imaging modality for the evaluation of bone marrow invasion and perineural tumor spread, which are findings critical for treatment planning. Advanced MR imaging techniques may potentially better delineate true tumor extent, determine lymph node metastases, and predict treatment response.

Bone repair and regeneration is a dynamic process that involves a complex interplay between the (1) ground substance, (2) cells, and (3) milieu. While each constituent is integral to the final product, it is often helpful to consider each component individually. Therefore, we created a two-part review to examine scaffolds and cells' roles in bone tissue engineering. In Part I, we review the myriad of materials use for in vivo bone engineering. In Part II, we discuss the variety cell types (e.g., osteocytes, osteoblasts, osteoclasts, chondrocytes, mesenchymal stem cells, and vasculogenic cells) that are seeded upon or recruited to these scaffolds. In Part III, we discuss the optimization of the microenvironment. The biochemical processes and sequence of events that guide matrix production, cellular activation, and ossification are vital to developing successful bone tissue engineering strategies and are thus succinctly reviewed herein.

PURPOSE: To compare vascularity and angiogenic activity in aggressive and nonaggressive giant cell lesions (GCLs) of the jaws. MATERIALS AND METHODS: This is a retrospective study of 14 GCLs treated at the University of California, San Francisco. Immunohistochemistry was used to determine of the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), CD34, and CD31. VEGF and bFGF expression in giant cells (GCs) and surrounding mononuclear stroma was classified into 1) high immunoreactivity (>50% staining) and 2) low immunoreactivity (<50% staining). CD31- and CD34-stained vessels were counted at 200x magnification. Clinical and radiographic records were reviewed to classify lesions as aggressive or nonaggressive. RESULTS: Of the lesions, 8 were aggressive and 6 were nonaggressive. High VEGF expression was found within the GCs in 4 of 8 aggressive lesions compared with 1 of 6 nonaggressive lesions. The stroma in both groups had low staining. High staining of the GCs for bFGF was found in 6 of 8 aggressive lesions compared with 3 of 6 nonaggressive lesions. The stroma of all aggressive cases showed high expression of bFGF compared with 3 of 6 nonaggressive cases. The aggressive group had a mean of 20.1 +/- 5.4 vessels/high-powered field (hpf) stained for CD31 compared with 11.5 +/- 5.6 vessels/hpf in the nonaggressive group. The aggressive group had 24.6 +/- 7.0 vessels/hpf stained with CD34 compared with 18.5 +/- 4.0 vessels/hpf in the nonaggressive group. CONCLUSIONS: The vascularity and level of angiogenesis within aggressive GCLs are higher than those in nonaggressive lesions.