Faculty Bibliography

BACKGROUND: Recent evolutions of oncologic breast surgery and reconstruction now allow surgeons to offer the appropriate patients a single-stage, autologous tissue reconstruction with the least donor-site morbidity. The authors present their series of buried free flaps in nipple-sparing mastectomies as proof of concept, and to explore indications, techniques, and early outcomes from their series. METHODS: From 2001 to 2011, a total of 2262 perforator-based free flaps for breast reconstruction were reviewed from the authors' prospectively maintained database. RESULTS: There were 338 free flaps performed on 215 patients following nipple-sparing mastectomy, including 84 patients who underwent breast reconstruction with 134 buried free flaps. Ductal carcinoma in situ and BRCA-positive were the most common diagnoses, in 26 patients (30.9 percent) each. The most common flaps used were the deep inferior epigastric perforator (77.6 percent), transverse upper gracilis (7.5 percent), profunda artery perforator (7.5 percent), and superficial inferior epigastric artery flaps (3.7 percent). An implantable Cook-Swartz Doppler was used to monitor all buried flaps. Fat necrosis requiring excision was present in 5.2 percent of breast reconstructions, and there were three flap losses (2.2 percent). Seventy-eight flaps (58.2 percent) underwent minor revision for improved cosmesis; 56 (41.8 percent) needed no further surgery. CONCLUSIONS: Nipple-sparing mastectomy with immediate autologous breast reconstruction can successfully and safely be performed in a single stage; however, the authors are not yet ready to offer this as their standard of care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

BACKGROUND: The classic Le Fort III procedure was recommended in syndromic craniosynostotic children to reduce exorbitism, improve airway function, and decrease dysmorphism. This study reports on a cohort of syndromic craniosynostosis patients who have undergone early primary subcranial (classic Tessier) Le Fort III advancement and who have been followed longitudinally through skeletal maturity and beyond. METHODS: In this study, the Le Fort III advancements all occurred between the ages of 3 to 5 years, with a mean age of 4.6 years. Subsequently, these early Le Fort III patients were followed throughout development with longitudinal dental, medical, radiographic, and photographic evaluations conducted through skeletal maturity and beyond. For study inclusion, the patients had to have preoperative medical photographs and cephalometric studies at 6 months and 1, 5, and 10 years postoperatively after the primary Le Fort III advancement as well as cephalometric documentation 6 months and 1 year after the secondary midface advancement after skeletal maturity. RESULTS: After early or primary Le Fort III advancement, there was no evidence of relapse and only minimal anterior or horizontal postoperative growth of the midface. However, there was also a return of occlusal disharmony from "anticipated" mandibular growth, approaching a maximum at skeletal maturity. The dysmorphic concave facial profile and malocclusion, and airway and ocular considerations, provided the impetus for secondary midface surgery after skeletal maturity was attained. CONCLUSION: The data demonstrate that early Le Fort III advancement performed before the age of mixed dentition does not obviate the need for a secondary advancement after skeletal maturity is reached. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Cisplatin is the primary chemotherapy for head and neck squamous cell carcinoma (HNSCC). No equally effective chemotherapeutics are available when cisplatin resistance occurs. We hypothesize that DNA methylation of key genes mediates cisplatin resistance; moreover, pretreatment with decitabine, a demethylating agent, restores cisplatin sensitivity by mediating expression of genes that are instrumental to cisplatin resistance. Objectives: 1) Determine whether decitabine treatment of a cisplatin-resistant HNSCC cell line restores the anti-proliferative and apoptotic effects of cisplatin; 2) Evaluate the anti-proliferative effect of decitabine and cisplatin (i.e. combination treatment) on a preclinical HNSCC model; 3) Determine whether combination treatment reduces cancer pain; and 4) Create a "gene expression profile of cisplatin resistance" by analyzing cisplatinsensitive and cisplatin-resistant HNSCC in patients. Methods: SCC-25, a cisplatin-sensitive HNSCC cell line, and SCC-25/CP, a cisplatin-resistant cell line, were pre-treated with 5mM decitabine and then treated with cisplatin (3-300 mM) for 48 hours. Proliferation was quantified with an MTS assay. Apoptosis was quantified with a caspase 3/7 assay. A preclinical model was created by inoculating SCC-25/CP cells into the hind-paw of BALB/ c mice. Twenty-four mice were placed into one of four treatment groups: control sham, decitabine-only, cisplatin- only, or combination treatment. Decitabine (6 mg/kg) was administered on post-inoculation days (PID) seven and nine, and cisplatin (6 mg/kg) was administered on PID 12, 15, 18, and 21. Tumor growth was quantified. Mechanical allodynia (i.e. pain) was quantified with a paw withdrawal assay. Formalin-fixed, paraffin- embedded biopsies were obtained from HNSCC patients who underwent chemotherapy with cisplatin. Tumors were classified as either cisplatin-sensitive (RECIST 3 or 4) or cisplatin-resistant (RECIST 1 or 2). Gene expression was quantified in these two sets of samples. Results: In the in !

Statement of the Problem: Reconstruction of the atrophic edentulousmaxilla canbe a challenge, particularly in individuals where extensive bone grafting is required prior to dental implant placement or in patients where bone grafts have been tried and failed. Likewise, dental rehabilitation after tumor ablation and reconstruction can be problematic if there is inadequate maxillary bone to support traditional dental implants. Zygomaticus implants, which make use of the dense type I-II bone of the zygoma, are one solution that allows for dental implant reconstruction of the atrophic or reconstructed maxilla. Materials and Methods, Data Analysis: We performed a retrospective chart review of all patients who received dental implants in the operating room at two of our affiliated hospitals from June 2007 to March 2013. We identified those patients who received either unilateral or bilateral zygomaticus implants.We then collected available data including gender, diagnosis, adjunctive surgical procedures, and indication for zygomaticus implants. Patients receiving zygomaticus implants following maxillectomy procedures were compared to a cohort of patients who did not receive implants following maxillectomy to determine which variables may have influenced surgeon choice of zygomaticus implants. In addition, we report on two recent cases of zygomaticus implants placed followingenucleation of maxillary bone cysts. Follow-up was available for all patients and ranged from one month to five years. All implants were placed by and with the supervision of a single attending surgeon, DLH. Results: From 2007 to 2013, a total of 25 zygomaticus implants were placed in 12 patients at two affiliated hospitals. Indications for zygomatic implants were varied. Patients received zygomatic implantation for cleft reconstruction, maxillectomy defect with and without free tissue transfer, and atrophic maxilla not amenable to traditional implant surgery. Two patients received bilateral zygomaticus implants for a diagnosis of !

Statement of Problem: According to the Centers for Disease Control (CDC), approximately 26.5 million Americans carry a diagnosis of heart disease, over 2.6 million have atrial fibrillation, and as many as half of a million people are diagnosed with deep vein thromboses (DVT) or pulmonary embolisms (PE) each year.1 As the American population ages and rates of obesity increase, each of those statistics are expected to rise over the foreseeable future. Many of the patients afflictedwith these diagnoses take anticoagulant medications as part of their daily regimen. Oral and maxillofacial surgeons work in one of the most vascular parts of the body, the head and neck. As the statistics indicate, surgeons can expect to frequently encounter patients taking one or more medications that can prolong bleeding or inhibit proper clot formation. As new drugs enter the market, it is important for oral and maxillofacial surgeons to be aware of the pharmacology of these medications and the proper approaches to treating patients taking them. Methods: We undertook a comprehensive review of common outpatient anticoagulant medications, both new and old. Recommendations and guidelines from organizations such as the American Heart Association and the American Society of Hematology were analyzed and compiled with emphasis placed on perioperative management in both elective and emergent situations. Results: The traditional anticoagulants and antiplatelet agents reviewed were low molecular weight heparin, warfarin, fondaparinux, acetylsalicylic acid, and clopidogrel. New medications reviewed include dabigatran, prasugrel, ticagrelor, apixaban and rivaroxaban.2-5 Conclusion: Oral and maxillofacial surgeons can expect to frequently encounter patients taking anticoagulant and anti-platelet medications. It is extremely important to be aware of the risks of surgical treatment while patients are taking these drugs and equally important to be aware of emergency protocols for medication reversal, if possible. We seek to propose !

Statement of the Problem: The use of free osseous flaps has become the gold standard for reconstruction of complex mandibular defects. Popularized by Hidalgo1 in 1989, the free fibula transfer has become the operation of choice for these indications. While this operation has become routine; contouring of the flap using wedge osteotomies, as well as its inset remain operator dependent and imprecise. At our institution we have attempted to make this process more uniform and reproducible through the use of virtual planning and pre-fabricated cutting jigs. We have previously reported our experience on computer-aided design and manufacturing;2 however the purpose of this study was to review our series of free fibula mandibular reconstructions using these adjunctive technologies. Methods: Prior to surgery all patients underwent CT scanning of the face and bilateral lower extremities. These images were then transmitted to an outside vendor. In consultation with both the ablative and reconstructive teams, a surgical plan was devised and performed virtually, cutting jigs for both creation of the mandibular defect and for fibular osteotomies were fabricated, and a stereolithicmodel that allows for precise pre-surgical bending of a reconstruction platewas created. The rest of the surgical procedure was performed in standard fashion. Following IRB approval, all cases between 2009 and 2012 were identified and retrospectively reviewed. In addition to patient demographics, the charts were reviewed for surgical indications, microvascular anastomoses, use of a skin paddle, use of a "double barrel", timing of dental implant placement (immediate versus delayed), and timing of dental prosthetic rehabilitation (immediate versus delayed). Methods of Data Analysis: This was a retrospective chart review from 2009 to the present. Fifty-four reconstructionswere identified as having undergone presurgical virtual planning and subsequent surgery for mandibular reconstruction with microvascular free fibula transfer. Patient!

This study evaluated 3 implant surfaces in a dog model: (1) resorbable-blasting media + acid-etched (RBMa), alumina-blasting + acid-etching (AB/AE), and AB/AE + RBMa (hybrid). All of the surfaces were minimally rough, and Ca and P were present for the RBMa and hybrid surfaces. Following 2 weeks in vivo, no significant differences were observed for torque, bone-to-implant contact, and bone-area fraction occupied measurements. Newly formed woven bone was observed in proximity with all surfaces.

OBJECTIVES:: To investigate the effect of implant-abutment connection types on reliability and failure modes of anterior single-unit crowns. METHODS:: Fifty-four implants were divided in 3 groups (n = 18 each): external hexagon (EH), internal hexagon (IH), and Morse taper (MT) connection. Abutments were screwed to the implants, and maxillary central incisor metal crowns were cemented and subjected to step-stress accelerated life testing. RESULTS:: The beta values derived from use-level probability Weibull calculations for groups IH (2.52), EH (1.67), and MT (0.88) indicated that fatigue influenced the failure only of IH and EH groups. The reliability for a mission of 100,000 cycles at 175 N was 0.99 (0.98-1.00), 0.84 (0.62-0.94) and 0.97 (0.87-0.99) for the EH, IH, and MT, respectively. The characteristic strength was not significantly different between EH (290 N) and IH (251 N) but significantly higher for MT (357 N). For IH and EH groups, failure involved screw fracture, and the MT implants primary failure mode was abutment fracture. CONCLUSIONS:: Reliability was higher for the EH and MT relative to IH groups, whereas the characteristic strength was significantly higher for implants with MT connection.

The mechanotransduction mechanisms linking distraction device activation to new bone formation remain unknown. We hypothesize that the tension stress of activation during distraction osteogenesis is transmitted through lacunocanalicular fluid flow to initiate the osteogenic signaling cascade. Adult Sprague-Dawley rats (N = 24) were subjected to mandibular osteotomy and application of an external distraction device. After a 3-day latency period, half the animals (n = 12) underwent device activation at 0.25 mm twice daily for 6 days (total activation, 3 mm), and the other half (n = 12) had no activation. On day 10, the animals were injected with fluorescent reactive red lacunocanalicular tracer before killing. Mandibles were harvested, embedded, and sectioned, and reactive red epifluorescence lacunocanalicular flow was measured. Protein was harvested for focal adhesion kinase 1 (FAK1), NESPRIN1, SUN1, LAMIN A/C, and SMAD1 Western blotting as well as for bone morphogenetic protein (BMP)-2 enzyme-linked immunosorbent assay and alkaline phosphatase assay. Lacunocanalicular fluid flow was significantly greater in the distracted samples (60.5 +/- 14 vs 10.3 +/- 4 molecules of equivalent soluble fluorochrome per megapixel, P = 0.01). Flow distribution demonstrated the highest lacunocanalicular flow near the center of the distraction gap. Increased lacunocanalicular flow resulted in increased FAK1 (P = 0.009), NESPRIN1 (P = 0.01), SUN1 (P = 0.01), and LAMIN A/C (P = 0.008) expression. Focal adhesion kinase 1 activation in the presence of BMP-2 protein expression (P = 0.001) resulted in increased intranuclear SMAD1 phosphorylation (P = 0.04) and alkaline phosphatase activity (P < 0.0001). These findings suggest that activation of the distraction osteogenesis device affects cellular response through changes in lacunocanalicular fluid flow.