Faculty Bibliography

In this study, we investigated the role of the peripheral endothelin-1 (ET-1) concentration in a cancer pain model. To test the hypothesis that the concentration of ET-1 in the tumor microenvironment is important in determining the level of cancer pain we used two cancer pain mouse models that differed significantly in production of ET-1. The two mouse cancer models were produced by injection of cells derived from a human oral squamous cell carcinoma (SCC) and melanoma into the hind paw of female mice. Pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, was significantly greater in the SCC group than the melanoma group. The peripheral concentration of ET-1 within the cancer microenvironment was significantly greater in the SCC group. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly higher in the SCC model compared to the melanoma model. ET receptor antagonism was effective as an analgesic for cancer pain in the SCC model only. To address the potential confounding factor of tumor volume we evaluated the contribution of tumor volume to cancer pain in the two models. The mean volumes of the tumors in the melanoma group were significantly greater than the tumors in the SCC group. In both groups, the pain level correlated with tumor volume, but the correlation was stronger in the melanoma group. We conclude that ET-1 concentration is a determinant of the level of pain in a cancer pain mouse model and it is a more important factor than tumor volume in producing cancer pain. These results suggest that future treatment regimens for cancer pain directed at ET-1 receptor antagonism show promise and may be tumor type specific

PURPOSE: Squamous cell carcinomas of the hard palate, maxillary gingiva, and maxillary alveolus occur at relatively low rates compared with squamous cell carcinomas in other oral sites. There is little within the surgical literature to guide treatment for maxillary squamous cell carcinoma. To date, only 1 other group has addressed neck management in the oral maxillary squamous cell carcinoma patient presenting with a clinically negative neck. Adequate characterization of maxillary gingival carcinoma behavior with respect to regional cervical metastasis is wanting. PATIENTS AND METHODS: We present a retrospective review of our own clinical experience as well as a review of the existing literature. RESULTS: In our University of California San Francisco patient group, cervical disease was detected in 20% of those individuals with maxillary squamous cell carcinoma presenting for initial consultation. After ablative surgery, those individuals who presented with clinically negative necks had a 21.4% rate of regional node metastasis. Ultimately, 50% of our patients with squamous cell carcinomas of the palate, maxillary gingiva, and maxillary alveolus developed regional or metastatic distant disease; 42.9% of the patients manifested disease to the cervical lymph nodes alone. CONCLUSIONS: The cases of oral maxillary squamous cell carcinomas reviewed herein exhibit aggressive regional metastatic behavior comparable to that of such carcinomas of the tongue, floor of the mouth, and mandibular gingiva. Based on the findings presented herein, we recommend selective neck dissection in the setting of a clinically negative neck as a primary management strategy for patients with oral maxillary squamous cell carcinomas involving the palate, maxillary gingiva, and maxillary alveolus

The aim of the present study was to evaluate the potential of acellular dermal matrix as a carrier for delivery of stem cells to the site of soft tissue defect in a murine skin injury model and to determine the potential of stem cells delivered via such an approach to successfully engraft, survive and differentiate locally. We showed that adipose-derived stem cells delivered via this matrix survived after in vivo engraftment, spontaneously differentiated along vascular endothelial, fibroblastic and epidermal epithelial lineages and significantly improved wound healing. Furthermore, an organ survey for transplanted cells showed no evidence of a systemic distribution beyond the cutaneous wound site, indicating that the adipose-derived stem cell-dermal matrix construct provides a novel and effective method for anatomically focused cellular therapy. In conclusion, stem cell-seeded dermal matrix is an effective means for targeted in vivo cell delivery for enhanced soft tissue regeneration.

INTRODUCTION: Methyl methacrylate is a biologically inert alloplastic material that is commonly used to rebuild the calvarial vault. Since methyl methacrylate does not permit tissue incorporation it is susceptible to displacement and/or fracture. In order to increase the tensile strength of methyl methacrylate onlay cranioplasties, we use wire reinforced masonry techniques. PATIENT: A 56-year-old female presents with forehead asymmetry due to displacement and fracture of a silicone alloplastic implant. This patient, treated with onlay wire reinforced methyl methacrylate, demonstrates the utility of this novel technique. RESULTS: Wire is passed through 2-mm outer cortex tunnels like spokes on a wheel, around the perimeter of the defect to form a rebar grid. Methyl methacrylate is poured onto the rebar grid and contoured after it solidifies. CONCLUSIONS: Wire reinforced methyl methacrylate is a simple technique to improve the tensile strength of calvarial alloplastic reconstructions

BACKGROUND: Gingivoperiosteoplasty has been shown to eliminate the need for secondary alveolar bone grafting in 60 percent of patients. The purpose of this study was to compare radiographic alveolar anatomy following infant gingivoperiosteoplasty, secondary alveolar bone grafting, and secondary alveolar bone grafting in patients who had prior infant gingivoperiosteoplasty with inadequate bone formation. METHODS: Seventy-four consecutive nonsyndromic patients (complete bilateral cleft lip-cleft palate, n = 12; complete unilateral cleft lip-cleft palate, n = 46; complete unilateral cleft lip and alveolus, n = 14) treated at New York University Medical Center were available for evaluation. Eighty-two complete alveolar cleft sites were assigned to three groups: gingivoperiosteoplasty (n = 30), secondary alveolar bone grafting (n = 41), and secondary alveolar bone grafting following gingivoperiosteoplasty (n = 11). All gingivoperiosteoplasties were performed at the time of primary lip surgery, and secondary alveolar bone grafting (cancellous iliac crest at 7 to 12.5 years of age) was performed before eruption of the permanent canine. Radiographs were measured according to the modified method of Long. RESULTS: Seventy-three percent of gingivoperiosteoplasty cases did not require secondary alveolar bone grafting and none had fistulas. The rate of missing teeth in the total sample, adjacent to the cleft, was within normal limits for the population. Group 1 alone and groups 1 and 3 combined had superior alveolar anatomy compared with group 2 (p < 0.01). No significant differences existed between groups 1 and 3 (p > 0.05). Crest height was best in group 1 (p < 0.01), followed by group 3 and then group 2, with no difference between the latter two groups. CONCLUSION: Gingivoperiosteoplasty alone or combined with secondary alveolar bone grafting results in superior bone levels when compared with conventional secondary alveolar bone grafting alone

BACKGROUND: The incidence of thyroid cancer in black Americans is half that in white Americans. It is unknown whether this gap represents a population difference in disease or is attributable to inferior cancer screening in the black population. METHODS: A population-based cohort study of 53,990 patients (1973-2003) was performed using the National Cancer Institute's Surveillance Epidemiology End Results database. Socioeconomic variables were explored using the Healthcare Cost and Utilization Project database and macroeconomic data. RESULTS: Since 1973, thyroid cancer incidence among whites has increased 150.2% (4.0 to 9.9 of 100,000), while incidence among blacks has increased 73.2% (3.0 to 5.1 of 100,000). Across 17 regions, the incidence correlated with the percentage of the population with health insurance (r = 0.56, P = .02). Regression analysis suggested that half of the black-white incidence gap might be attributable to differences in health insurance status. Patients with thyroid cancer were more likely to be insured or reside in wealthier ZIP codes. Black patients were more likely to present at advanced age (RR 1.08, P < .0001) and with tumors >4 cm in size (RR 1.13, P <.0001). Black patients were slightly less likely to present with advanced disease (RR 0.96, P = .0008). Cancer-specific mortality was identical in the two populations. DISCUSSION: Sociodemographic data and differences at presentation support a small detection disparity in thyroid cancer, which may contribute to part of the incidence gap. However, this effect is not sufficiently strong to fully explain the incidence gap. A population difference in the incidence of disease may be coexistent

BACKGROUND: Restoration of shoulder abduction is very important following obstetrical brachial plexus paralysis. The purpose of this report is to present the authors' experience of suprascapular nerve reconstruction in 53 cases of obstetrical brachial plexus palsy. METHODS: From 1978 to 2002, 170 children with obstetrical brachial plexus palsy were seen at the authors' institution. One hundred nine children underwent surgical treatment, and 53 of them had suprascapular nerve reconstruction. RESULTS: The overall results were good or excellent in 96 percent of patients for the supraspinatus muscle and 75 percent for the infraspinatus muscle. The overall mean postoperative muscle grading was 3.71 +/- 0.7 for the supraspinatus muscle and 2.94 +/- 0.8 for the infraspinatus muscle (p < 0.05). By using the Mallet score, 23 patients (46 percent) achieved Mallet grade III and 24 patients (48 percent) achieved Mallet grade IV shoulder abduction function. Evaluating external rotation function, 21 patients (42 percent) achieved Mallet grade III and 20 patients (40 percent) achieved Mallet grade IV. Early surgery (<6 months) yielded significantly better results than late surgery (>6 months). CONCLUSIONS: Suprascapular nerve neurotization is a worthwhile procedure and is a high priority in upper limb reanimation for restoration of glenohumeral joint stability, shoulder abduction, and external rotation. Concomitant neurotization of the axillary nerve yields improved outcomes in shoulder abduction function. The best results are seen in patients with high severity scores, when only the upper two roots are involved, and when direct neurotization of the suprascapular nerve is performed within 6 months after the injury

BACKGROUND: Diabetes impairs the ability of tissue to respond adequately to ischemia. The underlying mechanisms contributing to this impaired response remain unknown. Because increases in apoptosis have been linked to a spectrum of diabetic complications, the authors examined whether programmed cell death is involved in the pathogenesis of poor diabetic tissue responses to ischemia. METHODS: Analysis for apoptosis and levels of proaptotic protein, p53, were performed on streptozocin-induced diabetic mice and wild-type controls in a murine model of soft-tissue ischemia (n = 6). In vitro, chronic hyperglycemic culture conditions were used to test inducibility and reversibility of the diabetic phenotype. Small interfering RNA was used to assess the role of p53. RESULTS: Ischemia-induced apoptosis and p53 levels were increased significantly in diabetic dermal fibroblasts both in vivo and in vitro. Chronic hyperglycemic culture was sufficient to induce the increased apoptotic phenotype, and this was not reversible with long-term normoglycemic conditions. Blocking p53 with small interfering RNA resulted in significant protection against ischemic apoptosis. CONCLUSIONS: These findings suggest that diabetes causes an increased apoptotic response to ischemia through a p53-mediated mechanism. This increase is not reversible by exposure to low-glucose conditions. This suggests that glycemic control alone will be unable to prevent tissue necrosis in diabetic patients and suggests novel therapeutic strategies for this condition