Faculty Bibliography

This study evaluated the effect of microrobotized blasting of titanium endosteal implants relative to their manually blasted counterparts. Two different implant systems were utilized presenting two different implant surfaces. Control surfaces (Manual) were fabricated by manually grit blasting the implant surfaces while experimental surfaces (Microblasted) were fabricated through a microrobotized system that provided a one pass grit blasting routine. Both surfaces were created with the same ~50microm average particle size alumina powder at ~310KPa. Surfaces were then etched with 37% HCl for 20min, washed, and packaged through standard industry procedures. The surfaces were characterized through scanning electron microscopy (SEM) and optical interferometry, and were then placed in a beagle dog radius model remaining in vivo for 3 and 6 weeks. The implant removal torque was recorded and statistical analysis evaluated implant system and surface type torque levels as a function of time in vivo. Histologic sections were qualitatively evaluated for tissue response. Electron microscopy depicted textured surfaces for both manual and microblasted surfaces. Optical interferometry showed significantly higher Sa, Sq, values for the microblasted surface and no significant difference for Sds and Sdr values between surfaces. In vivo results depicted that statistically significant gains in biomechanical fixation were obtained for both implant systems tested at 6 weeks in vivo, while only one system presented significant biomechanical gain at 3 weeks. Histologic sections showed qualitative higher amounts of new bone forming around microblasted implants relative to the manually blasted group. Microrobotized blasting resulted in higher biomechanical fixation of endosteal dental implants and should be considered as an alternative for impant surface manufacturing.

BACKGROUND: Fat grafting has become popular for repair of postsurgical/postradiation defects after head/neck cancers resection. Fat graft supplementation with adipose tissue-derived stromal/stem cells (ASCs) is proposed to improve graft viability/efficacy, although the impact of ASCs on head/neck cancer cells is unknown. OBJECTIVES: To determine whether ASCs affect growth, migration, and metastasis of human head/neck cancer. METHODS: Human Cal-27 and SCC-4 head/neck cancer cells were co-cultured human ASCs, or treated with ASC conditioned medium (CM), and cancer cell growth/migration was assessed by MTT, cell count, and scratch/wound healing assays in vitro. Co-injection of 3 x 10(6) Cal-27/green fluorescent protein (GFP) cells and ASCs into the flank of NUDE mice assessed ASC effect on tumor growth/morphology. Quantitation of human chromosome 17 DNA in mouse organs assessed ASC effects on micrometastasis. Primary tumors were evaluated for markers of epithelial-to-mesenchymal transition, matrix metalloproteinases, and angiogenesis by immunohistochemistry. RESULTS: Co-culture of Cal-27 or SCC-4 cells with ASCs from 2 different donors or ASC CM had no effect on cell growth in vitro. However, ASC CM stimulated Cal-27 and SCC-4 migration. Co-injection of ASCs from 2 different donors with Cal-27 cells did not affect tumor volume at 6 weeks, but increased Cal-27 micrometastasis to the brain. Evaluation of tumors sections from 1 ASC donor co-injection revealed that ASCs were viable and well integrated with Cal-27/GFP cells. These tumors exhibited increased MMP2, MMP9, IL-8, and microvessel density. CONCLUSIONS: Human ASCs did not alter growth of human head/neck cancer cells or tumor xenografts, but stimulated migration and early micrometastasis to mouse brain.

Importance: Limited data exist on performing major oral cavity resections and reconstructions without elective tracheotomy. Objectives: To describe a group of patients who successfully underwent major microvascular mandibular reconstruction without an elective tracheotomy and to perform a literature review to identify commonalities between our group and the available literature to identify potential common factors that might contribute to the success of this approach. Design, Setting, and Participants: Case series with retrospective medical chart review of 15 patients who underwent fibula microvascular free flap reconstruction of mandibular defects without tracheotomy between 2000 and 2014 (the most common indication was osteoradionecrosis) conducted at a tertiary referral hospital center. Exposures: Mandibular reconstruction with fibula free flap without elective tracheotomy. Main Outcomes and Measures: Perioperative morbidity and mortality with a focus on airway management and perioperative complications. Results: The median age of 15 patients (11 males and 4 females) at the time of reconstruction was 42 years (range, 10-64 years). The indication for surgery was nonmalignant pathologic abnormalities in 8 patients (53%), osteosarcoma in 4 patients (27%), and oral cavity squamous cell carcinoma in 3 patients (20%). All patients were intubated endonasally and, excepting 1 pediatric case, were extubated the day following surgery. The fibula spanned the parasymphysis and/or symphysis in 2 patients, and was limited to the mandibular body in others (mean length, 7.6 cm [range, 4.0-15.0 cm]). The flap design was osteocutaneous in 3 patients and osseous in the rest. No patient required reintubation or tracheotomy. No complications due to endonasal intubation occurred. The average hospital length of stay was 11 days. Conclusions and Relevance: Major oral cavity resection and reconstruction with microvascular free flaps can be performed safely without elective tracheotomy in a select group of patients. Limited data exist on patient selection criteria. Further studies are needed to identify favorable factors and develop protocols for safe patient selection.

PURPOSE: There is considerable controversy over the treatment of medication-related osteonecrosis of the jaw (MRONJ) and growing interest and debate related to the timing, type, technique, and goals of surgical intervention. The specific aim was to evaluate the predictive value of fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) on healing outcomes in patients undergoing surgery for MRONJ of the mandible. MATERIALS AND METHODS: A retrospective cohort study of 31 patients with 33 MRONJ lesions of the mandible who had undergone surgery using FDG PET-CT was conducted. Data were collected on FDG uptake patterns, healing, follow-up, demographics, lesion characteristics, antiresorptive therapy, and adjunctive therapy. Panoramic and periapical radiographs were used to identify non-restorable teeth and PET-CT images were used to identify sequestra and FDG uptake. Above the mandibular canal, surgery consisted of marginal resection or debridement of clinically involved bone and exposure of clinically uninvolved bone identified by FDG uptake. Below the mandibular canal, mobile segments of bony sequestra were removed, but areas of clinically uninvolved bone with FDG uptake were not. Patients who did not heal underwent segmental resection and reconstruction with rigid fixation and a local or regional soft tissue flap or free fibular flap. The primary predictor variable was the FDG uptake pattern for each patient. The outcome variable was postoperative healing defined by mucosal closure without signs of infection or exposed bone at the time of evaluation. RESULTS: Two risk groups were identified based on FDG uptake pattern. The low-risk group, type A, included 22 patients with activity limited to the alveolus, torus, and basal bone superior to the mandibular canal. The high-risk group, type B, included 11 patients with type A FDG activity with extension inferior to the mandibular canal. Treatment of type A MRONJ lesions was more successful than treatment of type B MRONJ lesions (100 vs 27%; P < .001). Seven of the type B failures were successfully retreated by segmental resection and reconstruction (1 patient refused further treatment). CONCLUSION: These results showed that low-risk FDG PET-CT findings predicted successful healing with surgery above the mandibular canal. In contrast, high-risk FDG findings were associated with a greater than 50% risk of failure for treatment that extended below the mandibular canal. Although these failures suggest that FDG uptake indicates infected tissue, further research is needed to identify which high-risk patients are most likely to benefit from a conservative treatment protocol.

Chronic hyperglycemia impairs intracellular redox homeostasis and contributes to impaired diabetic tissue regeneration. The Keap1/Nrf2 pathway is a critical regulator of the endogenous antioxidant response system and its dysfunction has been implicated in numerous pathologies. Here, we characterize the effect of chronic hyperglycemia on Nrf2 signaling within a diabetic cutaneous regeneration model. We characterized the effects of chronic hyperglycemia on the Keap1/Nrf2 pathway within models of diabetic cutaneous wound regeneration. We assessed reactive oxygen species (ROS) production and antioxidant gene expression following alterations in the Nrf2 suppressor, Keap1, and the subsequent changes in Nrf2 signaling. We also developed a topical siRNA-based therapy to restore redox homeostasis within diabetic wounds. Western blot demonstrated that chronic hyperglycemia-associated oxidative stress inhibits nuclear translocation of Nrf2 and impairs activation of antioxidant genes, thus contributing to ROS accumulation. Keap1 inhibition increased Nrf2 nuclear translocation, increased antioxidant gene expression, and reduced ROS production to normoglycemic levels, both in vitro and in vivo. Topical siKeap1 therapy resulted in improved regenerative capacity of diabetic wounds and accelerated closure. We report that chronic hyperglycemia weakens the endogenous antioxidant response and the consequences of this defect are manifested by intracellular redox dysregulation, which can be restored by Keap1 inhibition. Targeted siRNA-based therapy represents a novel, efficacious strategy to reestablish redox homeostasis and accelerate diabetic cutaneous tissue regeneration.

Despite the many types of oral pathologic lesions found in infants and children, the most commonly encountered are benign soft tissue lesions. The clinical features, diagnostic criteria, and treatment algorithms of pathologies in the age group from birth to 18 years of age are summarized based on their prevalence in each given age distribution. Treatment modalities include both medical and surgical management.

INTRODUCTION: Long-term oncologic outcomes in nipple-sparing mastectomy (NSM) continue to be defined. Rates of locoregional recurrence for skin-sparing mastectomy (SSM) and NSM in the literature range from 0% to 14.3%. We investigated the outcomes of NSM at our institution. METHODS: Patients undergoing NSM at our institution from 2006 to 2014 were identified and outcomes were analyzed. RESULTS: From 2006 to 2014, 319 patients (555 breasts) underwent NSM. One-hundered and fourty-one patients (237 breasts) had long-term follow-up available. Average patient age and BMI were 47.78 and 24.63. Eighty-four percent of patients underwent mastectomy primarily for a therapeutic indication. Average tumor size was 1.50 cm with the most common histologic type being invasive ductal carcinoma (62.7%) followed by DCIS (23.7%). Average patient follow-up was 30.73 months. There was one (0.8%) incidence of ipsilateral chest-wall recurrence. There were 0.37 complications per patient. CONCLUSIONS: We examined our institutional outcomes with NSM and found a locoregional recurrence rate of 0.8% with no nipple-areolar complex recurrence. This rate is lower than published rates for both NSM and SSM. J. Surg. Oncol. (c) 2015 Wiley Periodicals, Inc.

OBJECTIVES: Narrow implants are indicated in areas of limited bone width or when grafting is nonviable. However, the reduction of implant diameter may compromise their performance. This study evaluated the reliability of several narrow implant systems under fatigue, after restored with single-unit crowns. MATERIALS AND METHODS: Narrow implant systems were divided (n = 18 each), as follows: Astra (ASC); BioHorizons (BSC); Straumann Roxolid (SNC), Intra-Lock (IMC), and Intra-Lock one-piece abutment (ILO). Maxillary central incisor crowns were cemented and subjected to step-stress accelerated life testing in water. Use level probability Weibull curves and reliability for a mission of 100,000 cycles at 130- and 180-N loads (90 % two-sided confidence intervals) were calculated. Scanning electron microscopy was used for fractography. RESULTS: Reliability for 100,000 cycles at 130 N was approximately 99 % in group ASC, approximately 99 % in BSC, approximately 96 % in SNC, approximately 99 % in IMC, and approximately 100 % in ILO. At 180 N, reliability of approximately 34 % resulted for the ASC group, approximately 91 % for BSC, approximately 53 % for SNC, approximately 70 % for IMC, and approximately 99 % for ILO. Abutment screw fracture was the main failure mode for all groups. CONCLUSIONS: Reliability was not different between systems for 100,000 cycles at the 130-N load. A significant decrease was observed at the 180-N load for ASC, SNC, and IMC, whereas it was maintained for BSC and ILO. CLINICAL RELEVANCE: The investigated narrow implants presented mechanical performance under fatigue that suggests their safe use as single crowns in the anterior region.