Faculty Bibliography

Cancers often cause excruciating pain and rapid weight loss, severely reducing quality of life in cancer patients. Cancer-induced pain and cachexia are often studied and treated independently, although both symptoms are strongly linked with chronic inflammation and sustained production of proinflammatory cytokines. Because nerve growth factor (NGF) plays a cardinal role in inflammation and pain, and because it interacts with multiple proinflammatory cytokines, we hypothesized that NGF acts as a key endogenous molecule involved in the orchestration of cancer-related inflammation. NGF might be a molecule common to the mechanisms responsible for clinically distinctive cancer symptoms such as pain and cachexia as well as cancer progression. Here we reported that NGF was highly elevated in human oral squamous cell carcinoma tumors and cell cultures. Using two validated mouse cancer models, we further showed that NGF blockade decreased tumor proliferation, nociception, and weight loss by orchestrating proinflammatory cytokines and leptin production. NGF blockade also decreased expression levels of nociceptive receptors TRPV1, TRPA1, and PAR-2. Together, these results identified NGF as a common link among proliferation, pain, and cachexia in oral cancer. Anti-NGF could be an important mechanism-based therapy for oral cancer and its related symptoms

The supraclavicular artery island (SAI) flap is a viable fasciocutaneous option for the reconstruction of head and neck defects. Although authors have reported success using SAI flaps for various reconstructive indications, concerns of a tenuous blood supply and distal ischemia have previously limited its use in the posterolateral skull base. This case series reports the outcomes of 5 consecutive patients receiving SAI flaps for posterolateral skull base reconstruction. All flaps were harvested in less than 1 hour with primary closure of all donor sites. A single patient developed superficial necrosis of the distal flap, which was repaired with a full-thickness skin graft. There were no other complications, and no donor site morbidity was observed. The SAI flap is an excellent option for the reconstruction of posterolateral skull base defects. The close color match, easy harvest within 1 hour, lack of microsurgical anastomosis, and absence of donor site morbidity support its continued utilization.

BACKGROUND: The authors' goal was to develop an updated and comprehensive algorithm for skull base reconstruction based on data from the 10-year period following their initial report. METHODS: Reconstructive outcomes were analyzed from 250 patients undergoing skull base reconstruction from 2000 to 2009. RESULTS: Thirty-nine local or regional pedicled flap reconstructions and 211 free flap reconstructions were performed. Free flaps were usually selected over pedicled flaps for patients with a history of prior surgery, irradiation, or chemotherapy (p = 0.003, p < 0.001, and p = 0.04, respectively). Reconstructions were performed for 36 region I defects, 39 region II defects, 124 region III defects, and 51 defects involving more than one region. Complications occurred in 29.6 percent of patients. There were no significant differences in the overall complication rates between pedicled and free flap reconstructions (p = 0.70). The recipient-site complication rate decreased from 31 percent in the authors' prior report to 18.4 percent. A facial nerve repair was performed in 30 patients. By 12 months, 75 percent of patients had signs of reinnervation. Recovery was not significantly less likely in patients with preoperative weakness, postoperative irradiation, or age 60 years or older (p = 1.00, p = 1.00, and p = 0.11, respectively). CONCLUSIONS: Based on the largest series of skull base reconstructions to date, the authors recommend pedicled flaps for limited defects because of minimal donor-site morbidity and shorter operative times and hospital stays. For extensive defects and cases involving prior surgery, irradiation, or chemotherapy, free flaps are preferred. Facial nerve repair should be attempted whenever feasible, even in the setting of preoperative weakness, anticipated postoperative irradiation, or advanced age. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The purpose of this pilot study was to investigate the response of hypoplastic temporomandibular joints (TMJs) to mandibular distraction osteogenesis. This preliminary study describes changes in 2 male patients with unilateral craniofacial microsomia who were 5 years of age at the time of surgery. Spin echo sequence images of the TMJs without contrast media in axial, coronal, and sagittal views, along with sagittal kinematics studies, were obtained with the use of magnetic resonance imaging (MRI) at: 1 month preoperatively (T1); immediately upon removal of distraction devices (T2), and 14 months postoperatively (T3). At the same time points spiral 3D computed tomography (CT) was used to image the TMJs. Both MRI and CT data obtained were assessed by standard, qualitative interpretation. Predistraction MRI and CT data documented a hemifacial microsomia type IIb deformity with hypoplasia of the condyle and a dysfunctional TMJ on the affected side. After distraction, the MRI and CT data in both patients demonstrated no changes in the nonaffected TMJs. However, on the affected and distracted side the following changes were observed: (1) formation of a rudimentary glenoid fossa and articular eminence; (2) functional displacements of the rudimentary condyle-disk complex; (3) well-defined visualization of the temporalis and lateral pterygoid muscles; (4) increased signal intensity radio-density of the pseudodisk fibrous tissue. Thus, both patients showed improvements in the morphology and function of the TMJ as well as in the associated skeletal and soft tissue components. It was concluded that following mandibular distraction in young children, improved form and function of the TMJ complex is demonstrable using MRI. [ABSTRACT FROM AUTHOR]

BACKGROUND: : Although bone repair is a relatively efficient process, a significant portion of patients fail to heal their fractures. Because adequate blood supply is essential to osteogenesis, the authors hypothesize that augmenting neovascularization by increasing the number of circulating progenitor cells will improve bony healing. METHODS: : Bilateral full-thickness defects were created in the parietal bones of C57 wild-type mice. Intraperitoneal AMD3100 (n = 33) or sterile saline (n = 33) was administered daily beginning on postoperative day 3 and continuing through day 18. Circulating progenitor cell number was quantified by fluorescence-activated cell sorting. Bone regeneration was assessed with micro-computed tomography. Immunofluorescent CD31 and osteocalcin staining was performed to assess for vascularity and osteoblast density. RESULTS: : AMD3100 treatment increased circulating progenitor cell levels and significantly improved bone regeneration. Calvarial defects of AMD3100-treated mice demonstrated increased vascularity and osteoblast density. CONCLUSIONS: : Improved bone regeneration in this model was associated with elevated circulating progenitor cell number and subsequently improved neovascularization and osteogenesis. These findings highlight the importance of circulating progenitor cells in bone healing and may provide a novel therapy for bone regeneration

PURPOSE: This study tested the hypothesis that early integration of plateau root form endosseous implants is significantly affected by surgical drilling technique. MATERIALS AND METHODS: Sixty-four implants were bilaterally placed in the diaphysial radius of 8 beagles and remained 2 and 4 weeks in vivo. Half the implants had an alumina-blasted/acid-etched surface and the other half a surface coated with calcium phosphate. Half the implants with the 2 surface types were drilled at 50 rpm without saline irrigation and the other half were drilled at 900 rpm under abundant irrigation. After euthanasia, the implants in bone were nondecalcified and referred for histologic analysis. Bone-to-implant contact, bone area fraction occupancy, and the distance from the tip of the plateau to pristine cortical bone were measured. Statistical analyses were performed by analysis of variance at a 95% level of significance considering implant surface, time in vivo, and drilling speed as independent variables and bone-to-implant contact, bone area fraction occupancy, and distance from the tip of the plateau to pristine cortical bone as dependent variables. RESULTS: The results showed that both techniques led to implant integration and intimate contact between bone and the 2 implant surfaces. A significant increase in bone-to-implant contact and bone area fraction occupancy was observed as time elapsed at 2 and 4 weeks and for the calcium phosphate-coated implant surface compared with the alumina-blasted/acid-etched surface. CONCLUSIONS: Because the surgical drilling technique did not affect the early integration of plateau root form implants, the hypothesis was refuted.

BACKGROUND: : Autologous bone grafts, often harvested from the iliac crest, are the criterion standard for secondary alveolar cleft repair. The best technique for harvest remains controversial. Minimally invasive techniques have been used for bone graft harvest in cleft patients, but outcome studies have been limited by small numbers of patients. METHODS: : A total of 104 patients undergoing bone grafting for alveolar cleft were reviewed. Fifty-five consecutive patients underwent minimally invasive iliac bone graft harvest using the Acumed power-driven trephine system performed by the same surgeon. These patients were compared with 49 control patients undergoing a similar procedure in which the traditional method of open iliac bone harvest with an osteotome was used. RESULTS: : Operative time for the bone graft harvest was significantly shorter with the Acumed device when compared with the osteotome (2.37 hours versus 3.26 hours, p < 0.001). Patients who underwent minimally invasive Acumed bone harvest required significantly less postoperative analgesia than did patients who underwent osteotome harvest, for both narcotic (0.31 mg/kg versus 1.64 mg/kg, p < 0.001) and nonnarcotic (15.1 mg/kg versus 27.2 mg/kg, p < 0.01) pain medication. Acumed patients had significantly less pain on discharge (0.26 versus 3.1 pain scores on a scale from 0 to 10, p < 0.001) and left the hospital more quickly (23.3 hours versus 30.1 hours, p < 0.001). CONCLUSION: : Minimally invasive bone graft harvest technique using the trephine system offers a superior alternative to the conventional open iliac bone harvest method for patients undergoing secondary alveolar cleft repair, with shorter operative time, decreased requirement for pain medications, less pain on discharge, and a shorter hospital stay. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, III.(Figure is included in full-text article.)

The Centers for Medicare & Medicaid Services' regulations regarding nonpayment for hospital-acquired conditions such as pressure ulcers have prompted a marked increase in focus on preventive care. Our hospital also used this change in payment policy as an opportunity to strengthen our pressure ulcer prevention practices. We used an 8-spoke prevention wheel to develop and implement practice changes that reduced pressure ulcer incidence from 7.3% to 1.3% in 3 years. Because it is about the journey, we will describe the mechanisms we designed and implemented, and identify strategies that worked or did not work as we promulgated a quality improvement process for pressure ulcer prevention in our large urban hospital center.

BACKGROUND: : Distraction osteogenesis has revolutionized the treatment of craniofacial deformities, but it is limited by lengthy consolidation periods and tenuous healing in certain clinical settings, such as irradiated tissue. In this study, the authors aim to investigate whether increasing neovascularization by progenitor cell mobilization accelerates bone formation during distraction. METHODS: : Sprague-Dawley rats aged 8 weeks (n = 36) were subjected to unilateral mandibular distraction with 3-day latency, 7-day activation (0.25 mm twice daily), and 21-day consolidation periods. From the beginning of the consolidation period, animals received daily injections of either AMD3100 (bone marrow progenitor cell mobilizing agent) or sterile saline. Animals were euthanized on postoperative day 31; mandibles were harvested; and bone regeneration was assessed using micro-computed tomography, immunohistochemistry, bone morphogenetic protein-2 enzyme-linked immunosorbent assay, and mechanical testing. RESULTS: : Immunohistochemistry demonstrated that AMD3100 treatment increased vascular density and bone formation. Micro-computed tomography and dual-emission x-ray absorptiometry demonstrated that AMD3100-treated animals had improved bone generation compared with sham-treated controls. Greater force was required on three-point testing to break AMD3100-treated bone. Bone morphogenetic protein-2 expression was up-regulated with AMD3100. Interestingly, the nondistracted contralateral hemimandibles treated with AMD3100 were also stronger than sham-treated counterparts. CONCLUSIONS: : Progenitor cell mobilization improves bone regeneration in a rat distraction model. Furthermore, because this effect is seen in healthy bone and in ischemic bone healing during distraction, the mechanism is not merely related to oxygenation, but could be a phenomenon of fluid flow