Clear cell sarcoma of the jaw: a case report and review of the literature.

Clear cell sarcoma (CSS) is a unique malignant soft tissue tumor that mainly occurs from the aponeurotic tissue and tendons of extremities. It is rare in the pediatric population. The tumor does not respond well to chemotherapy or irradiation. Complete surgical resection offers the best chance for a cure. Most studies have demonstrated poor prognosis of this tumor, if it is >5 cm. The literature suggests that local recurrence and distant metastasis are not uncommon even with wide resection and that late recurrence and metastasis commonly occur. This case report discusses CSS in the jaw of a pediatric patient. To our knowledge, this is the only case of CSS of the jaw.

Osteocutaneous free tissue transplantation for mandibular osteoradionecrosis.

OBJECTIVE: To describe the success rate, complications, and functional outcomes of patients who are treated with osteocutaneous free tissue transplantation for grade 4 mandibular osteoradionecrosis (ORN). DESIGN: Retrospective case series. SETTING: Tertiary care academic medical center. PATIENTS: Twelve patients (8 males, 4 females; mean age, 57.6 years) with grade 4 mandibular ORN. Three patients (25%) had a history of primary radiotherapy, two (17%) had previous concurrent chemoradiation, and seven (58%) had undergone postoperative adjuvant radiotherapy. Ten patients (83%) had previous major ablative surgery to treat the primary tumor and five (50%) had been reconstructed with a free tissue transplant prior to the onset of ORN. INTERVENTIONS: All patients underwent reconstruction with an osteocutaneous free tissue transplant for grade 4 mandibular ORN between 1999 and 2006. MAIN OUTCOME MEASURES: Successful treatment of mandibular ORN; major, minor, and late complications; gastrostomy tube (G-tube) dependence; speech and swallowing scores. RESULTS: Grade 4 mandibular ORN was successfully treated in eight (73%) evaluable patients. One patient (8%) died of a second primary tumor before the 12-month assessment. Eight patients (67%) had a major complication, three (25%) had a minor complication, and nine (75%) had a late complication. Three of the five G-tube- dependent patients prior to mandibular reconstruction were able to discontinue the use of their G-tube. Seven of the eight successfully treated patients maintained their nutrition by mouth. Median "range of liquids" score was 6/6 (range, 4 to 6). Median "range of solids" score was 4/6 (range, 3 to 6). Median "understandability of speech" score was 4/5 (range, 2 to 5). CONCLUSIONS: Grade 4 mandibular ORN was treated successfully with an osteocutaneous free tissue transfer in eight evaluable patients (73%). In successfully treated patients, median speech/swallowing scores were highly functional, but the remaining radiated soft tissue resulted in higher local wound complications and a modified diet.

Glossectomy for the treatment of oral cavity carcinoma: Quantitative, functional and patient-reported quality of life outcomes differ by four glossectomy defects.

OBJECTIVE: The goal was to characterize four clinically distinct glossectomy defects to establish significant quantitative cut points using functional metrics, the MD Anderson Dysphagia Index (MDADI) and speech intelligibility. METHODS: Population included 101 patients treated with surgery, adjuvant radiation per NCCN guidelines, and ≥ 12 months follow-up. RESULTS: Defect groups: subtotal hemiglossectomy (1), hemiglossectomy (2), extended hemiglossectomy (3) and oral glossectomy (4) were compared: All outcomes supported a four defect model. Intergroup comparison of outcomes with subtotal hemiglossectomy as reference (p value): Tongue Protrusion <0.001,<0.001,<0.001; Elevation <0.001,<0.001,<0.001; Open Mouth Premaxillary Contact Elevation <0.001,<0.001,<0.001; Obliteration 0.6,<0.001,<0.001; Normalcy of Diet, <0.3,<0.001,<0.001; Nutritional Mode, <0.9,<0.8,<0.001; Range of Liquids, <0.4,<0.016,<0.02; Range of Solids, <0.5,<0.004,<0.001; Eating in Public, <0.2,<0.002,<0.03; Understandability of Speech, <0.9,<0.001,<0.001; Speaking in Public, <0.4,<0.03,<0.001; MDADI, <0.4,<0.005,<0.01; Single Word Intelligibility, <0.4,<0.1,<0.001; Sentence Intelligibility, <0.5,<0.08,<0.001; Words Per Minute Intelligibility, <0.6,<0.04,<0.001; Sentence Efficiency Ratio, <0.4,<0.03,<0.002. Proportion of patients by 4 defect groups who underwent: tissue transplantation, 51%,93.9%,100%,100%.Radiation,24%,67%,88%,80%.Between hemiglossectomy and extended hemiglossectomy, the defect extends into the contralateral floor of the mouth and/or the anterior tonsillar pillar; resection of these subunits limits tongue mobility with an impact on functional outcome and MDADI. Between extended hemiglossectomy and oral glossectomy, the defect extends to include the tip of the tongue and appears to impact functional outcome and MDADI. CONCLUSIONS: Subtotal hemiglossectomy, hemiglossectomy, extended glossectomy and oral glossectomy are associated with quantitative (elevation, protrusion, open mouth premaxillary contact and obliteration), qualitative (speech and swallowing) and MDADI differences, suggesting that these 4 ordinal defect groups are distinct.

The impact of surgical resection margins on outcomes for adults with head and neck osteosarcomas: A Canadian sarcoma research and Clinical Collaboration (CanSaRCC) study.

OBJECTIVE: The aim of the study is to describe the factors that influence outcome in adults with head and neck osteosarcoma (HNO) with a specific focus on the margin status. METHODS: Patients with a diagnosis of HNO between the years 1996-2021 were reviewed from the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) Database. Baseline characteristics, pathology, treatment, and outcomes were analyzed. Univariable (UVA) and multivariable (MVA) Cox regression models were performed. 5-year locoregional control rate and overall survival (OS) were estimated using Kaplan-Meier method and Log-Rank test. RESULTS: Of 50 patients with a median age of 40 years (range 16-80), 27 (54%) were male. HNO commonly involved the mandible (n = 21, 42%) followed by maxilla (n = 15, 30%). Thirteen (33.3%) had low-intermediate grade and 26 (66.6%) had high grade tumors. Three patients (6%) had negative resection margins (>5 mm), 24 (48%) had close margins (1-5 mm), 15 (30%) had positive margins (<1mm) and 7 (16%) had unknown margin status. In total, 39 (78%) received chemotherapy - 22 (44%) received neoadjuvant chemotherapy while 17 (34%) received adjuvant chemotherapy. A total of 12 (24%) patients received radiotherapy, of whom 8 (16%) had adjuvant and 3 (6%) had neo-adjuvant. Median follow-up time was 6.3 years (range 0.26-24.9). Disease recurred in 21 patients (42%), of whom 15 (30%) had local recurrence only, 4 (8%) had distant metastasis, and 2 (4%) had both local and distant recurrence. 5-year locoregional control rate and OS was 62% and 79.2% respectively. Resection margins <3 mm was associated with lower 5 years OS and locoregional control rate (Log-Rank p = 0.02, p = 0.01 respectively). CONCLUSION: Osteosarcomas of the head and neck are rare and local recurrence remains a concern. Surgical resection with negative resection margins may improve survival, and a 3 mm resection margin threshold may optimize survival. Radiotherapy and/or chemotherapy should be considered in a multidisciplinary setting based on risk-features.

Association of Plate Contouring With Hardware Complications Following Mandibular Reconstruction.

OBJECTIVES/HYPOTHESIS: Despite considerable effort being dedicated to contouring reconstruction plates, there remains limited evidence demonstrating an association between contour and reconstructive outcomes. We sought to evaluate whether optimizing mandibular reconstruction plate contouring is associated with reduced postoperative hardware complications. STUDY DESIGN: Retrospective cohort study. METHODS: A cohort study was performed with adult patients (age ≥18 years) who underwent mandibulectomy and osseous free flap reconstruction following oncologic ablation at the University Health Network in Toronto, Canada, between January 1, 2003 and December 31, 2014. Patients with computed tomography scans performed within 1 year of reconstruction were included. Computer-based three-dimensional models were generated and used to calculate the mean plate-to-bone gap (mm). The primary outcome was plate exposure. Secondary outcome included a composite of plate exposure or intraoral dehiscence. Logistic regression models were fitted for each outcome accounting for other patient and surgical characteristics associated with the primary outcome. RESULTS: Ninety-four patients met inclusion criteria, with a mean age of 60.4 (standard deviation [SD] 14.9). The mean follow-up time was 31.4 months (range 3-94). Reconstruction was performed with fibular (57%) and scapular free flaps (43%). In the multivariable model, small mean plate-to-bone gap (<1 mm) was independently associated with 86% reduced odds of plate exposure (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.02-0.55). Mean plate-to-bone gap less than 1 mm was also independently associated with reduced odds of developing a composite of plate exposure or intraoral dehiscence (OR, 0.29; 95%CI, 0.11-0.75). CONCLUSION: Optimizing plate contouring during mandibular reconstruction may decrease the development of postoperative hardware complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:61-66, 2022.

Short-term and long-term unstimulated saliva flow following unilateral vs bilateral radiotherapy for oropharyngeal carcinoma.

BACKGROUND: We aimed to compare unstimulated saliva flow using 3-minute modified Schirmer test (MST) following bilateral vs unilateral radiotherapy (RT) in oropharyngeal carcinoma (OPC). METHODS: We reviewed OPC patients treated with definitive intensity-modulated radiation therapy (IMRT) between 2011 and 2017. MST was measured at baseline, 1-/6-/12-/24-month post-RT. MST values were compared between bilateral-RT vs unilateral-RT groups. Multivariable logistic regression analysis (MVA) identified predictors of hyposalivation (MST < 25 mm). RESULTS: Total 498 bilateral-RT and 36 unilateral-RT patients were eligible. The MST values at 1-/6-/12-/24-month post-RT were all significantly reduced from baseline for the entire cohort. Baseline unilateral-RT and bilateral-RT MST values (in mm) were similar (P = .2), but much higher for unilateral-RT 1-month (mean: 19.1 vs 13.0, P = .03), 6-month (20.5 vs 9.3, P < .001), 12-month (20.1 vs 11.9, P < .01), and 24-month post-RT (22.2 vs 13.9, P = .04). MVA confirmed that unilateral RT reduced the likelihood of hyposalivation vs bilateral RT (OR 2.36, P = .006). CONCLUSION: Unilateral RT reduces unstimulated salivary flow in OPC patients.

Preoperative MR angiography in free fibula flap transfer for head and neck cancer: clinical application and influence on surgical decision making.

OBJECTIVE: We review the fibular free flap surgical procedure to illustrate the usefulness of preoperative lower limb MR angiography and to show how calf vascular anatomy on MR angiography affects patient surgical management. CONCLUSION: With its high positive predictive value and sensitivity, preoperative MR angiography can improve the chances of a successful outcome at the recipient mandibular site. It provides the reconstructive surgeon with a road map, revealing vascular anomalies or disease that could alter or contraindicate surgery.

Role of parathyroid hormone in regeneration of irradiated bone in a murine model of mandibular distraction osteogenesis.

BACKGROUND: The purpose of this study was to measure the histologic and histomorphometric effects of parathyroid hormone (PTH) treatment on irradiated bone undergoing distraction osteogenesis (DO). METHODS: Thirty-four rats were divided into 3 groups. The control group underwent DO and the radiation control group underwent radiotherapy (RT) before DO. The PTH group underwent RT and received PTH during DO. Quantitative histology and histomorphometry were performed. RESULTS: RT resulted in a depletion of osteocytes and increase in empty lacunae. Treatment with PTH resulted in an increase in osteocyte counts and decrease in empty lacunae (p < .05), restoring osteocytes to levels seen in nonradiated bone (p = .121). RT decreased bone volume to tissue volume (BV-TV) ratio and increased osteoid volume to tissue volume (OV-TV) ratio, signifying increased immature bone formation. PTH treatment restored OV-TV ratio to that observed in nonradiated bone. CONCLUSION: PTH treatment of irradiated bone enhanced bone regeneration and restored osteocyte counts and OV-TV ratio to levels comparable to nonradiated bone. © 2016 Wiley Periodicals, Inc. Head Neck 39: 464-470, 2017.

Hardware complications in oromandibular defects: Comparing scapular and fibular based free flap reconstructions.

BACKGROUND: Despite improvements in surgical technique and technology, hardware complications occur relatively frequently. This study analyzes hardware complications in patients undergoing oromandibular reconstruction using scapular (SFF) or fibular (FFF) free flaps. METHODS: Retrospective data for 178 patients was obtained (1999-2014) at University Hospital Network (Toronto, Canada). Univariable and multivariable analyses were performed to identify risk factors for hardware complications. RESULTS: Patients with FFF reconstruction (n=129) had significantly more hardware complications than those with SFF (n=49) (16% vs. 2%;p=0.01). Surgical site infection (SSI) (OR=7.05; p<0.01), defect type (OR=2.63; p<0.01) and flap (OR=0.12; p=0.01) were significant predictors of hardware complications on univariable analysis. Flap type (OR=0.12; p=0.04) was an independent predictor of plate complication after adjusting for SSI. A subgroup analysis suggested a trend towards fewer hardware complications with SFF stratified by mandibular defect type. CONCLUSIONS: Scapular free flaps are associated with a lower rate of hardware-related complications in oromandibular reconstruction.

Hemiglossectomy tongue reconstruction: Modeling of elevation, protrusion, and functional outcome using receiver operator characteristic curve.

BACKGROUND: The purpose of this study was to model >12 month speech and the oral phase of swallowing outcomes with the reconstructive metrics of tongue elevation and protrusion in patients reconstructed with the rectangle tongue template for a hemiglossectomy defect. METHODS: We conducted a study using 40 surviving patients (23 men, 17 women) treated between 2000 and 2012. Statistically significant correlations of elevation and protrusion with functional outcomes were modeled with receiver operator characteristic (ROC) curves to understand the performance and reliability of the rectangle tongue reconstruction. RESULTS: Tongue elevation (1.8-1.9 cm) reliably produces best outcomes in nutritional mode, range of liquids, and ≥4/6 for range of solids. Greater tongue elevation (2.1-2.2 cm) reliably produces best outcomes for eating and speaking in public and understandability of speech. Tongue protrusion (0.8-1.0 cm) reliably produces best scores across all assessed outcomes except ≥4/6 for range of solids and ≥4/5 understandability of speech. CONCLUSION: ROC curves are useful for assessing reliability and relating reconstructive objectives to functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1066-1073, 2016.

Translational treatment paradigm for managing non-unions secondary to radiation injury utilizing adipose derived stem cells and angiogenic therapy.

BACKGROUND: Bony non-unions arising in the aftermath of collateral radiation injury are commonly managed with vascularized free tissue transfers. Unfortunately, these procedures are invasive and fraught with attendant morbidities. This study investigated a novel, alternative treatment paradigm utilizing adipose-derived stem cells (ASCs) combined with angiogenic deferoxamine (DFO) in the rat mandible. METHODS: Rats were exposed to a bioequivalent dose of radiation and mandibular osteotomy. Those exhibiting non-unions were subsequently treated with surgical debridement alone or debridement plus combination therapy. Radiographic and biomechanical outcomes were assessed after healing. RESULTS: Significant increases in biomechanical strength and radiographic metrics were observed in response to combination therapy (p < .05). Importantly, combined therapy enabled a 65% reduction in persisting non-unions when compared to debridement alone. CONCLUSION: We support the continued investigation of this promising combination therapy in its potential translation for the management of radiation-induced bony pathology. © 2015 Wiley Periodicals, Inc. Head Neck 38: E837-E843, 2016.

Radiotherapy Characteristics and Outcomes for Head and Neck Carcinoma of Unknown Primary vs T1 Base-of-Tongue Carcinoma.

Importance: Transoral robotic surgery- or transoral laser microsurgery-assisted lingual tonsillectomy may improve the identification rate of hidden base-of-tongue (BOT) carcinoma presenting as head or neck carcinoma of unknown primary (CUP) site. Objective: To evaluate the potential impact of lingual tonsillectomy in CUP site by comparing differences in radiotherapy volumes, dosimetry, and clinical outcomes for CUP site and T1-category BOT carcinoma. Design, Setting, and Participants: Retrospective study of 115 patients treated at a tertiary cancer center between January 1, 2005, and December 31, 2013, that included patients with BOT carcinoma (category T1N1-3M0) and CUP site (category T0N1-3M0) with known p16 status. Fifty-four patients with T1-category BOT carcinoma (50 [92.6%] p16-positive) were treated with definitive intensity-modulated radiotherapy (IMRT), including 34 (63%) who received concurrent chemotherapy. Sixty-one patients with CUP site (38 [62.3%] p16-positive) received definitive (42 [68.9%]) or postoperative (19 [31.1%]) IMRT, including 22 (36%) who received concurrent chemotherapy. Interventions: Definitive or postoperative IMRT, with or without concurrent chemotherapy. Main Outcomes and Measures: Characteristics of mucosal clinical target volume (CTV-T), nodal CTV, and organ-at-risk dosimetry; local, regional, and distant control; cause-specific and overall survival; and Radiation Therapy Oncology Group grade 3 or higher late toxic effects. Results: Of 115 participants, 104 (90.4%) were male; mean (SD) age was 59 (10) years. High-dose CTV-T was prescribed in all 54 patients with BOT carcinoma and 23 (37.7%) with CUP site (effect size [Δ], 62%; 95% CI, 50%-74%). Low-dose CTV-T included mucosal pharyngeal sites outside the oropharynx in no patients with BOT carcinoma and 26 (42.6%) (95% CI, 30%-54%) with CUP site, with greater low-dose CTV-T volume in CUP site than BOT carcinoma (113 vs 84 cm3; Δ, 30 cm3; 95% CI, 10-49 cm3). Bilateral neck irradiation was used in 53 of 54 patients (98.1%) with BOT carcinoma and 46 of 61 (75.4%) with CUP site (Δ, 23%; 95% CI, 12% to 34%). Patients with BOT carcinoma received a higher maximum dose to the mandible (71 vs 67.2 Gy; Δ, 3.8 Gy; 95% CI, 1.6 to 6 Gy), with a nonsignificantly higher maximum dose (66.1 vs 62.8 Gy; 3.2 Gy; 95% CI, -0.1 to 6.5 Gy) and lower mean dose to the larynx (43.8 vs 47.1 Gy; 3.3 Gy; 95% CI, -0.3 to 6.9 Gy). There were no significant differences in local control, regional control, distant control, cause-specific survival, and overall survival between the BOT carcinoma and CUP site groups stratified by p16 status. Grade 3 Radiation Therapy Oncology Group late toxic effects occurred in 2 patients (3.3%) with CUP site (both neck fibrosis) and 5 (9.3%) with BOT carcinoma (2 neck fibrosis, 2 osteoradionecrosis, and 1 dysphagia). Conclusions and Relevance: Intensity-modulated radiotherapy for CUP site or T1-category BOT carcinoma had similar clinical outcomes. Identifying hidden BOT primary carcinoma with novel approaches (eg, transoral robotic surgery and transoral laser microsurgery) may lead to changes in the radiotherapy target volume and dose prescription. Studies are needed to investigate the effect of these differences on quality of life and functional outcomes.

Osseocutaneous radial forearm free tissue transfer for repair of complex midfacial defects.

OBJECTIVE: To evaluate the resulting aesthetics, function, and donor site morbidity of the osseocutaneous radial forearm free flap (OCRFFF) used for midface reconstruction. DESIGN: Prospective case series and a retrospective review of results. PATIENTS: Ten patients from an academic practice who underwent reconstruction at the University of Michigan Hospitals between 1995 and 2001. INTERVENTIONS: All patients had maxillectomy defects in which the entire infraorbital rim was reconstructed with an OCRFFF. Of the 10 patients included in the study, 3 underwent a total maxillectomy with orbital exenteration, 4 had a total maxillectomy without orbital exenteration, and 3 had a limited maxillectomy that did not involve the palate. Patients with palatal defects underwent reconstruction with a prosthetic palatal obturator. MAIN OUTCOME MEASURES: Facial contour and aesthetic results, speech understandability, ability to eat solid foods, oronasal separation, socializing outside the home, and return-to-work status. Flap success, donor site morbidity, and orbital complications were also studied. RESULTS: Mean +/- SEM follow-up was 23.2 +/- 5.0 months. A modified Funk facial deformity scale was used, and 7 of the 10 patients had either no deformity or minimal deformity. The mean aesthetic score for these reconstructions was 2.1 +/- 0.3 on a scale of 1 to 4, with 1 representing no deformity and 4 representing a severe deformity. All patients returned to a solid diet and had understandable speech, although patients who had an orbital exenteration trended to poorer scores. All patients socialized either frequently or occasionally outside the home, and all patients not retired or disabled prior to surgery returned to work. CONCLUSION: The OCRFFF reconstruction of the infraorbital rim in patients with total maxillectomy defects and obturator of the palatal defect controls orbital complications and optimizes aesthetic outcome while achieving nearly normal palatal function.

Tissue engineering: the current status of this futuristic modality in head neck reconstruction.

PURPOSE OF REVIEW: To define tissue engineering and describe the components that are involved in engineering tissue. To provide examples of the most recent developments in tissue engineering as they apply to the otolaryngologist. To provide a general overview of selected exciting advances outside the field of general otolaryngology but of general interest to the reconstructive community. RECENT FINDINGS: Tissue engineering is a rapidly evolving field that can be defined as the regeneration of new tissues through the use of biologic mediators and matricis. The three components required are scaffolds, signaling molecules, and cells. A significant amount of work has been done to generate bone, cartilage, cornea, and vascular grafts. Tissue engineered bone is the only tissue type that has been evaluated in Phase III clinical trials and is in routine clinical use. Engineered bone from BMP-2 and BMP-7 is used in orthopedics for lumbar fusions and long bone nonunions. Clinical application of bone tissue engineering in the head and neck is limited to case reports. There has been success in tissue engineering with cartilage for the nose and ear in immune incompetent animal models but there has been difficulty with generating scaffolds that do not incite an immune reaction in an immune competent model. The most advanced organ engineered is a bladder that has been successful in a canine model. SUMMARY: Tissue engineering holds the promise of "off the shelf" parts for reconstruction of tissues and organs. The widest clinical application is with bone in orthopedics. Applications in the head and neck are limited, at present, due to the immunogenicity of the scaffolds and the challenging wounds encountered in both cancer and cosmetic patients.

Efficacy of induction selection chemotherapy vs primary surgery for patients with advanced oral cavity carcinoma.

IMPORTANCE: The University of Michigan has investigated the use of induction selection (IS) with chemoradiotherapy (CRT) for patients who respond to CRT and found this approach effective in the management of advanced laryngeal cancer. The IS approach was extended to oral cavity squamous cell carcinoma (OCSCC) to help understand whether organ preservation or survival benefit resulted. OBJECTIVE: To evaluate the efficacy of an IS protocol vs primary surgical extirpation and selective postoperative radiotherapy for advanced OCSCC. DESIGN AND SETTING: Retrospective matched cohort study at a tertiary care hospital. PARTICIPANTS: Nineteen patients with resectable stages III and IV OCSCC were enrolled into a phase 2 IS trial. Patients with a response of at least 50% underwent concurrent CRT; those with a response of less than 50% underwent surgical treatment and radiotherapy. A comparison cohort of patients treated with primary surgical extirpation during a similar time period was frequency matched for inclusion criteria and patient characteristics to those patients included from the phase 2 IS trial. No difference was noted in age, sex, pretreatment American Joint Committee on Cancer stage, T and N classifications, smoking status, alcohol consumption, or tumor subsite between the IS and surgical cohorts. Median follow-up was 9.4 years in the IS cohort and 7.1 years in the surgical cohort. INTERVENTIONS: Induction selection and CRT vs primary surgical extirpation with or without postoperative radiotherapy. MAIN OUTCOMES AND MEASURES: Overall and disease-specific survival and locoregional control. RESULTS: The Kaplan-Meier estimate for overall survival at 5 years was 32% in the IS cohort and 65% in the surgical cohort. The Kaplan-Meier estimate for disease-specific survival at 5 years was 46% in the IS cohort and 75% in the surgical cohort. The Kaplan-Meier estimate for locoregional control at 5 years was 26% in the IS cohort and 72% in the surgical cohort. Multivariable analysis demonstrated significantly better overall and disease-specific survival and locoregional control outcomes (P = .03, P = .001, and P < .001, respectively) in the surgical cohort. CONCLUSIONS AND RELEVANCE: Primary surgical treatment showed significantly better survival and locoregional control compared with IS in this matched patient cohort. Despite success of organ preservation IS protocols in the larynx, comparative survival analysis of an IS protocol vs primary surgical extirpation for OCSCC demonstrates significantly better outcomes in the surgical cohort. These findings support surgery as the principal treatment for OCSCC.

Parathyroid hormone therapy mollifies radiation-induced biomechanical degradation in murine distraction osteogenesis.

OBJECTIVE: Descriptions of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis have been limited. Previous work demonstrated radiation decreases union formation, cellularity and mineral density in mandibular distraction osteogenesis. The authors posit that intermittent systemic administration of parathyroid hormone will serve as a stimulant to cellular function, reversing radiation-induced damage and enhancing bone regeneration. METHODS: Twenty male Lewis rats were randomly assigned to three groups: group 1 (radiation and distraction osteogenesis, n = 7) and group 2 (radiation, distraction osteogenesis, and parathyroid hormone, n = 5) received a human-equivalent dose of 35 Gy of radiation (human bioequivalent, 70 Gy) fractionated over 5 days. All groups, including group 3 (distraction osteogenesis, n = 8), underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Distraction osteogenesis was performed at a rate of 0.3 mm every 12 hours to reach a gap of 5.1 mm. Group 2 was injected with parathyroid hormone (60 µg/kg) subcutaneously daily for 3 weeks after the start of distraction osteogenesis. On postoperative day 40, all left hemimandibles were harvested. Biomechanical response parameters were generated. Statistical significance was considered at p ≤ 0.05. RESULTS: Parathyroid hormone-treated mandibles had significantly higher failure load and higher yield than did untreated mandibles. However, these values were still significantly lower than those of nonirradiated mandibles. CONCLUSIONS: The authors have successfully demonstrated the therapeutic efficacy of parathyroid hormone to stimulate and enhance bone regeneration in their irradiated murine mandibular model of distraction osteogenesis. Anabolic regimens of parathyroid hormone, a U.S. Food and Drug Administration-approved drug on formulary, significantly improve outcomes in a model of postoncologic craniofacial reconstruction.

Role of parathyroid hormone therapy in reversing radiation-induced nonunion and normalization of radiomorphometrics in a murine mandibular model of distraction osteogenesis.

BACKGROUND: The use of mandibular distraction osteogenesis (MDO) for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis has been described but, in fact, has seen limited clinical utility. Previous laboratory work has shown that radiation (XRT) causes decreased union formation, decreased cellularity, and decreased mineral density in an animal model of MDO. Our global hypothesis is that radiation-induced bone damage is partly driven by the pathologic depletion of both the number and function of osteogenic cells. Parathyroid hormone (PTH) is a U.S. Food and Drug Administration-approved anabolic hormonal therapy that has demonstrated efficacy for increasing bone mineral density for the treatment of osteoporosis. We postulate that intermittent systemic administration of PTH will serve as an anabolic stimulant to cellular function that will act to reverse radiation-induced damage and enhance bone regeneration in a murine mandibular model of DO. METHODS: A total of 20 isogenic male Lewis rats were randomly assigned into 3 groups. Group 1 (XRT-DO, n = 7) and group 2 (XRT-DO-PTH, n = 5) received a human bioequivalent dose of 70 Gy fractionated over 5 days. All groups including group 3 (DO, n = 8) underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Four days later, mandibular DO was performed at a rate of 0.3 mm every 12 hours to reach a maximum gap of 5.1 mm. Group 2 was injected PTH (60 µg/kg) subcutaneously daily for 3 weeks following the start of MDO. On postoperative day 41, all left hemimandibles were harvested. Micro-CT at 45-µm voxel size was performed and radiomorphometrics parameters of bone mineralization were generated. Union quality was evaluated on a 4-point qualitative grading scale. Radiomorphometric data were analyzed using 1-way ANOVA, and union quality assessment was analyzed via the Mann-Whitney test. Statistical significance was considered at p ≤ .05. RESULTS: Groups 1 and 2 appropriately demonstrated clinical signs of radiation-induced stress ranging from alopecia to mucositis. Union quality was significantly higher in PTH-treated XRT-DO animals, compared with XRT-DO group animals (p = .02). Mineralization metrics, including bone volume fraction (BVF) and bone mineral density (BMD), also showed statistically significant improvement. The groups that were treated with PTH showed no statistical differences in union or radiomorphometrics when compared with DO in nonradiated animals. CONCLUSION: We have successfully demonstrated the therapeutic efficacy of PTH to stimulate and enhance bone regeneration in our irradiated murine mandibular model of DO. Our investigation effectively resulted in statistically significant increases in BMD, BVF, and clinical unions in PTH-treated mandibles. PTH demonstrates immense potential to treat clinical pathologies where remediation of bone regeneration is essential.

Parathyroid hormone reverses radiation induced hypovascularity in a murine model of distraction osteogenesis.

BACKGROUND: Radiation treatment results in a severe diminution of osseous vascularity. Intermittent parathyroid hormone (PTH) has been shown to have an anabolic effect on osteogenesis, though its impact on angiogenesis remains unknown. In this murine model of distraction osteogenesis, we hypothesize that radiation treatment will result in a diminution of vascularity in the distracted regenerate and that delivery of intermittent systemic PTH will promote angiogenesis and reverse radiation induced hypovascularity. MATERIALS AND METHODS: Nineteen Lewis rats were divided into three groups. All groups underwent distraction of the left mandible. Two groups received radiation treatment to the left mandible prior to distraction, and one of these groups was treated with intermittent subcutaneous PTH (60 µg/kg, once daily) beginning on the first day of distraction for a total duration of 21 days. One group underwent mandibular distraction alone, without radiation. After consolidation, the rats were perfused and imaged with micro-CT angiography and quantitative vascular analysis was performed. RESULTS: Radiation treatment resulted in a severe diminution of osseous vascularity in the distracted regenerate. In irradiated mandibles undergoing distraction osteogenesis, treatment with intermittent PTH resulted in significant increases in vessel volume fraction, vessel thickness, vessel number, degree of anisotropy, and a significant decrease in vessel separation (p < 0.05). No significant difference in quantitative vascularity existed between the group that was irradiated, distracted and treated with PTH and the group that underwent distraction osteogenesis without radiation treatment. CONCLUSIONS: We quantitatively demonstrate that radiation treatment results in a significant depletion of osseous vascularity, and that intermittent administration of PTH reverses radiation induced hypovascularity in the murine mandible undergoing distraction osteogenesis. While the precise mechanism of PTH-induced angiogenesis remains to be elucidated, this report adds a key component to the pleotropic effect of intermittent PTH on bone formation and further supports the potential use of PTH to enhance osseous regeneration in the irradiated mandible.

Transoral resection of pharyngeal cancer: summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia.

Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6-7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)-initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized.

Revascularized tissue transplant and internal transport disk distraction osteogenesis for the reconstruction of complex composite mandibular defects.

OBJECTIVE: To assess the feasibility of internal transport disk distraction osteogenesis (ITDDO) for the regeneration of segmental mandibular defects and to evaluate the effect of radiation therapy. DESIGN: Prospective case series. SETTING: Tertiary care academic medical centre. METHODS: Nine patients were accrued (M:F 6:3; mean age 63 years, range 37-77 years) and underwent ITDDO for the regeneration of segmental mandibular defects. The mean follow-up time was 43 months (range 6-87 months). The average bony defect was 6.1 cm (range 3.0-10.0 cm). MAIN OUTCOME MEASURES: Construct formation (graded as complete, partial, and none based on evidence of calcification on panorex films and palpation), complications, and plate exposure (grouped by those that were thought to be related to distraction and those that were independent of distraction). RESULTS: Construct formation was "complete" in two of nine patients (22%), "partial" in four of nine (44%), "none" in two of nine (22%), and one of nine patients (11%) died prior to the 6 month assessment point. Four patients did not undergo radiation therapy, and two had stable constructs 6 years after treatment completion. Five patients underwent radiation therapy, and none of these patients formed stable, ossified constructs. All patients experienced a complication, and seven of nine (78%) developed hardware exposure, with six contributing to construct loss. CONCLUSIONS: Construct formation with ITDDO is possible for large composite mandibular defects in patients who have not received radiation. The complication rate was unacceptably high but may improve with better patient selection, refinement in surgical technique and distractor design, and tissue engineering for construct support.