Faculty Bibliography

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

We investigated the cannabinoid receptor (CBr) agonists Win55,212-2 (non-selective) and AM1241 (CBr2 selective) and the peripheral receptor (CBr1) in carcinoma-induced pain using a mouse model. Tumors were induced in the hind paw of female mice by local injection of a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at 4 days after SCC inoculation and lasted to 18 days. Local administration of Win55,212-2 (10 mg/kg) and AM1241 (10 mg/kg) significantly elevated withdrawal thresholds, indicating an antinociceptive effect. Ipsilateral expression of CBr1 protein in L5 DRG was significantly upregulated compared to ipsilateral L4 DRG and in normal tissue. These findings support the suggestion that cannabinoids are capable of producing antinociception in carcinoma-induced pain

This study presents the in-vivo evaluation of Ti-13Nb-13Zr alloy implants obtained by the hydride route via powder metallurgy. The cylindrical implants were processed at different sintering and holding times. The implants' were characterized for density, microstructure (SEM), crystalline phases (XRD), and bulk (EDS) and surface composition (XPS). The implants were then sterilized and surgically placed in the central region of the rabbit's tibiae. Two double fluorescent markers were applied at 2 and 3 weeks, and 6 and 7 weeks after implantation. After an 8-week healing period, the implants were retrieved, non-decalcified section processed, and evaluated by electron, UV light (fluorescent labeling), and light microscopy (toluidine blue). BSE-SEM showed close contact between bone and implants. Fluorescent labeling assessment showed high bone activity levels at regions close to the implant surface. Toluidine blue staining revealed regions comprising osteoblasts at regions of newly forming/formed bone close to the implant surface. The results obtained in this study support biocompatible and osseoconductive properties of Ti-13Nb-13Zr processed through the hydride powder route. © 2007.

BACKGROUND: Since the National Surgical Adjuvant Breast and Bowel Project B06 (NSABP-B06) trial demonstrated equivalent survival outcomes between patients with breast cancer undergoing modified radical mastectomy versus lumpectomy and radiation, an increasing number of patients are seeking breast conservation therapy. Traditionally, only patients who have undergone total mastectomy have been referred for reconstruction. OBJECTIVE: The purpose of the study was to determine the number of dissatisfied patients treated with breast conservation therapy who have suboptimal cosmesis and should be referred for reconstruction. METHODS: After obtaining approval from the Institutional Review Board and patient consent, patients identified as more than 1 year posttreatment from breast conservation therapy (1999-2004) were interviewed and photographed. Data were gathered by use of a questionnaire that included patient aesthetic score, patient satisfaction, and change in body image. Photographs were shown to a surgical oncologist, a general surgeon, and a plastic surgeon for a physician aesthetic score. RESULTS: Thirteen of 46 patients (28.3%) were dissatisfied with their cosmetic result. Women who were dissatisfied with their cosmetic result were more likely to have a negative change in their body image when compared with patients who were satisfied with their cosmetic result (46.2 % vs 6.1%, P = .02). Additionally, dissatisfied patients were more likely to rate their cosmetic result as poor (15.4 % vs 0%, P = .007) and were more likely to consider reconstruction (46.2% vs 9.1%, P = .01) when compared with satisfied patients. Risk factors to predict dissatisfaction in our patient population included age younger than 52 years and the resection of tumor from the upper inner quadrant. CONCLUSIONS: Twenty-eight percent of patients in this study were dissatisfied with their cosmetic result. Furthermore, a large portion of these patients would consider reconstruction if it were offered. Although this study only identified a few broad risk factors for suboptimal cosmetic outcome, it confirms our hypothesis that many patients who have undergone breast conservation therapy should be referred for plastic surgery consultation

PURPOSE: Resecting oral squamous cell carcinoma (SCC) with an appropriate margin of uninvolved tissue is critical in preventing local recurrence and making the decision regarding postoperative radiation therapy. This task can be difficult due to the discrepancy between margins measured intraoperatively and those measured microscopically by the pathologist after specimen processing. The goal of this study is to quantify and compare the amount of margin discrepancy observed based on tumor location and staging. MATERIALS AND METHODS: Forty-one patients who underwent resective surgery with curative intent for primary oral SCC were included in this study. All patients underwent resection of the tumor with a measured 1 cm margin by one attending surgeon. Specimens were then submitted for processing and reviewing and histopathologic margins were measured. The closest histopathologic margin was compared with the in situ margin (1 cm) to determine percentage discrepancy. Percent discrepancies were grouped by locations (buccal mucosa, mandibular alveolar ridge, and retromolar trigone in group 1; maxillary alveolar ridge and palate in group 2; and oral tongue in group 3) and analyzed. Percent discrepancies grouped by stages T1/T2 or T3/T4 were compared. RESULTS: The mean discrepancy for all patients was a statistically significant 59.02% (P < .0001). The mean discrepancy was 71.90% for group 1, 53.33% for group 2, and 42.14% for group 3 (P = .0133). The mean discrepancy in T1/T2 tumors was 51.48% and in T3/T4 tumors was 75.00% (P = .0264). CONCLUSIONS: Oral SCC margin discrepancies after resection and specimen processing are highly significant. Tumors located in the buccal mucosa, retromolar trigone, and mandibular alveolar ridge show significantly greater discrepancies than tumors of the maxilla or oral tongue. Late stage tumors also show significantly greater margin discrepancies. These findings suggest that it might be prudent to consider oral site and staging when outlining margins to ensure adequacy of resection

OBJECTIVES: Kaposi sarcoma (KS) is a vascular tumor that can affect the mucosa of the upper aerodigestive tract. Although KS is the most common malignancy in patients with acquired immunodeficiency syndrome, it is rare in immunocompetent persons. We describe an unusual presentation of KS in 2 related individuals and describe our attempts to determine whether oropharyngeal KS is associated with human herpesvirus 8 (HHV-8). METHODS: All relevant clinical and surgical information, including information on tumor histopathologic and human immunodeficiency virus (HIV) serologic tests, was abstracted from the patient charts and electronic databases. HHV-8 immunohistochemistry was performed on paraffin-fixed specimens. RESULTS: Both patient 1 and patient 2 (the nephew of patient 1) were referred for workup of a tonsillar mass that was pathologically confirmed to be KS. In each case, HIV serologic testing was negative, and a screening immunologic workup, including a quantitative natural killer cell count, a B- and T-lymphocyte count, and immunoglobulin analysis, also yielded findings that were within normal limits. Immunohistochemistry performed on 1 pathological specimen showed positive staining for the presence of HHV-8, the etiologic agent of KS. CONCLUSIONS: The presence of oropharyngeal KS in 2 related HIV-negative individuals supports a role for genetic factors in susceptibility to KS, a common exposure to an infectious agent such as HHV-8, or both. Whereas most KS cases in industrialized countries are associated with immunodeficiency, clinical and laboratory data do not suggest that either of the patients described in this report are immunodeficient. Their susceptibility to KS may be secondary to a subtle inherited defect in host resistance to HHV-8, or another unknown factor

To date, reports on the incidence and distribution of pediatric facial fractures have been inconsistent and have originated only from institutional studies. The need for current national data exists. We examined the Kids' Inpatient Database and the Nationwide Inpatient Sample to obtain national information on facial fracture discharges from 1997 to 2003. Data showed that pediatric patients (age, 0-17 years) make up 14.7% of all facial fractures, with children aged 1 to 4 years comprising only 5.6% of the total and children 15 to 17 years old making up more than half the group. The male-to-female ratio was 2.5. Significantly lengthier hospitalizations were observed with female patients, Medicaid insurance, teaching hospitals, government hospitals, and metropolitan hospitals. Significantly higher charges were associated with patients aged 1 to 4 years, Medicaid insurance, Western US geography, teaching hospitals, metropolitan hospitals, and children's hospitals. During the 6-year period of this study, there was a trend toward (1) increased hospital charges (with stable costs), (2) more patients treated at teaching hospitals, and (3) a convergence in length of stay between hospitals with differing ownerships (with government hospitals having progressively shorter hospitalizations, whereas private for-profit hospitals have progressively lengthier hospitalizations). The incidence of facial fractures in children is small yet significant and has remained stable during the past few decades. Certain patient populations are prone to facial fractures, and various patient and hospital factors are associated with lengthier and more expensive hospitalizations. An understanding of disparities in resource use among various patient, hospital, and geographic settings is critical for physicians and policy makers.