Hybrid Core-Shell Polymer Scaffold for Bone Tissue Regeneration.

A great promise for tissue engineering is represented by scaffolds that host stem cells during proliferation and differentiation and simultaneously replace damaged tissue while maintaining the main vital functions. In this paper, a novel process was adopted to develop composite scaffolds with a core-shell structure for bone tissue regeneration, in which the core has the main function of temporary mechanical support, and the shell enhances biocompatibility and provides bioactive properties. An interconnected porous core was safely obtained, avoiding solvents or other chemical issues, by blending poly(lactic acid), poly(ε-caprolactone) and leachable superabsorbent polymer particles. After particle leaching in water, the core was grafted with a gelatin/chitosan hydrogel shell to create a cell-friendly bioactive environment within its pores. The physicochemical, morphological, and mechanical characterization of the hybrid structure and of its component materials was carried out by means of infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and mechanical testing under different loading conditions. These hybrid polymer devices were found to closely mimic both the morphology and the stiffness of bones. In addition, in vitro studies showed that the core-shell scaffolds are efficiently seeded by human mesenchymal stromal cells, which remain viable, proliferate, and are capable of differentiating towards the osteogenic phenotype if adequately stimulated.

A cost-utility analysis comparing CT surveillance, PET-CT surveillance, and planned postradiation neck dissection for advanced nodal HPV-positive oropharyngeal cancer.

BACKGROUND: The cost utility of image-guided surveillance using computed tomography (CT) and positron emission tomography (PET)-CT to planned postradiation neck dissection (PRND) was compared for the management of advanced nodal human papillomavirus-positive oropharyngeal cancer following chemoradiation. METHODS: A universal payer perspective was adopted. A Markov model was designed to simulate four treatment approaches with 3-month cycles over a lifetime horizon: 1) CT surveillance, 2) standard PET-CT surveillance, 3) a novel PET-CT approach with repeat PET at 6 months postchemoradiation for equivocal responders, and 4) PRND. Parameters including probabilities of CT nodal progression/resolution, PET avidity, recurrence, and survival were obtained from the literature. Costs were reported in 2019 Canadian dollars and utilities were expressed in quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. RESULTS: PET-CT surveillance dominated CT surveillance and PRND in the base case scenario, and the novel PET-CT approach was the most cost-effective strategy across a wide range of variables tested in one-way sensitivity analysis. On probabilistic sensitivity analysis, novel PET-CT surveillance was the most cost-effective strategy in 78.1% of model iterations at a willingness-to-pay of $50,000/QALYs. Novel PET-CT surveillance resulted in a 49% lower rate of neck dissection compared with traditional PET-CT, and yielded an incremental benefit of 0.14 QALYs with average cost savings of $1309. CONCLUSIONS: Image-guided surveillance including PET-CT and CT are more cost effective than PRND. The novel PET-CT approach with repeat PET for equivocal responders was the dominant strategy and yielded both higher benefit and lower costs compared with standard PET-CT surveillance.

Comparing Contour Restoration of Mandibular Body Defects With Fibula, Iliac Crest, and Scapular Tip Flaps: A Conformance Virtual Study.

PURPOSE: The purpose of this study was to determine which of the most commonly used flaps restore contour more accurately in mandibular body reconstructions using conformance analyses and virtual measurements. METHODS: Using normal computed tomography (CT) scans and a 3D software, mandibular body defects were virtually created. "Single shot" and osteotomized fibula flaps (SS-FF and O-FF), iliac crest flaps (ICF) and scapular tip flaps (STF) were digitally harvested and coregistered to reconstruct those defects. Conformance analyses were performed by calculating the root mean square (RMS) for overall and contour conformance. RESULTS: Ten patients normal CT scans were included. The STF demonstrated improved overall conformance compared with the ICF, the SS-FF and the O-FF (RMS = 2.03 mm vs 4.53 mm vs 2.76 vs 2.37 mm, respectively; p<.001). Similar trends were seen for contour conformance in STF compared with the ICF and the SS-FF (RMS = 2.48 mm vs 4.50 mm vs 3.28 mm, respectively), whereas the O-FF performed better than STF (RMS = 1.85 mm vs 2.48 mm; p<.001). CONCLUSIONS: The osseous component of the STF resembles the mandibular body more accurately than the one in the ICF and FF without the need for an osteotomy. Future clinical studies can help to elucidate the clinical impact of these virtual findings.

Hypofractionated radiotherapy alone with 2.4 Gy per fraction for head and neck cancer during the COVID-19 pandemic: The Princess Margaret experience and proposal.

BACKGROUND: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT-hypo) during the COVID-19 pandemic. METHODS: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT-hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT-acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005-2017 were included. Locoregional control (LRC) and distant control (DC) after RT-hypo, RT-acc, and CCRT were compared for various subgroups. RESULTS: The study identified 994 human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT-hypo, RT-acc, and CCRT, respectively) and 1045 HPV- HNSCC cases (with 263, 451, and 331 receiving RT-hypo, RT-acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy-alone patients were older. The median follow-up was 4.6 years. RT-hypo, RT-acc, and CCRT produced comparable 3-year LRC and DC for HPV+ T1-2N0-N2a disease (seventh edition of the TNM system [TNM-7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1-T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1-2N2c/T3N0-N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT-hypo or RT-acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV- HNSCC, 3-year LRC and DC were similar with RT-hypo, RT-acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT-hypo and RT-acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT-acc (62%) but not RT-hypo (80%) or CCRT (92%; RT-hypo vs CCRT: P = .270; RT-acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT-hypo or RT-acc in stage IV (73%, 65%, and 66%; P = .336). CONCLUSIONS: It is proposed that RT-hypo be considered in place of CCRT for HPV+ T1-T3N0-N2c (TNM-7) HNSCCs, HPV- T1-T2N0 HNSCCs, and select stage III HNSCCs during the COVID-19 outbreak.

Development and validation of a Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN-HN) in a scarce resource setting: Response to the COVID-19 pandemic.

BACKGROUND: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, access to surgical care for patients with head and neck cancer (HNC) is limited and unpredictable. Determining which patients should be prioritized is inherently subjective and difficult to assess. The authors have proposed an algorithm to fairly and consistently triage patients and mitigate the risk of adverse outcomes. METHODS: Two separate expert panels, a consensus panel (11 participants) and a validation panel (15 participants), were constructed among international HNC surgeons. Using a modified Delphi process and RAND Corporation/University of California at Los Angeles methodology with 4 consensus rounds and 2 meetings, groupings of high-priority, intermediate-priority, and low-priority indications for surgery were established and subdivided. A point-based scoring algorithm was developed, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN-HN). Agreement was measured during consensus and for algorithm scoring using the Krippendorff alpha. Rankings from the algorithm were compared with expert rankings of 12 case vignettes using the Spearman rank correlation coefficient. RESULTS: A total of 62 indications for surgical priority were rated. Weights for each indication ranged from -4 to +4 (scale range; -17 to 20). The response rate for the validation exercise was 100%. The SPARTAN-HN demonstrated excellent agreement and correlation with expert rankings (Krippendorff alpha, .91 [95% CI, 0.88-0.93]; and rho, 0.81 [95% CI, 0.45-0.95]). CONCLUSIONS: The SPARTAN-HN surgical prioritization algorithm consistently stratifies patients requiring HNC surgical care in the COVID-19 era. Formal evaluation and implementation are required. LAY SUMMARY: Many countries have enacted strict rules regarding the use of hospital resources during the coronavirus disease 2019 (COVID-19) pandemic. Facing delays in surgery, patients may experience worse functional outcomes, stage migration, and eventual inoperability. Treatment prioritization tools have shown benefit in helping to triage patients equitably with minimal provider cognitive burden. The current study sought to develop what to the authors' knowledge is the first cancer-specific surgical prioritization tool for use in the COVID-19 era, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN-HN). This algorithm consistently stratifies patients requiring head and neck cancer surgery in the COVID-19 era and provides evidence for the initial uptake of the SPARTAN-HN.

Orbital Floor Reconstruction: 3-Dimensional Analysis Shows Comparable Morphology of Scapular and Iliac Crest Bone Grafts.

PURPOSE: Current nonvascular osseous reconstructive options for reconstruction of the orbital floor after maxillectomy include options such as scapular tip and iliac crest bone grafts. The aim of this study was to determine whether these donor sites were morphologically comparable with the orbital floor. MATERIALS AND METHODS: A retrospective cross-sectional study design was selected. By use of a pre-existing melanoma database (January 1, 2005, through September 20, 2015), computed tomography scans of the head, neck, thorax, and pelvis were obtained from patients without evidence of bony metastases. With the use of 3-dimensional software (Mimics; Materialise, Leuven, Belgium), grafts from the scapulae and iliac crests, the predictor variables, were digitally harvested, co-registered with the orbital floors bilaterally, and analyzed. The primary outcome was conformance. Data were analyzed using descriptive statistics and tests of statistical significance. The significance level was set at P<.05. RESULTS: The study sample included 10 patients (6 men and 4 women; mean age, 55 ± 18 years). Close conformance was observed when we analyzed the morphology of the orbital floor to the scapular (2.23 ± 0.31 mm) and iliac crest (2.13 ± 0.30 mm) bone grafts, with no significant difference between sites. Conformance mapping showed maximum conformance centrally (scapula, 0.001 ± 0.001 mm; iliac crest, 0.001 ± 0.001 mm), with decreased morphologic similarity peripherally (scapula, 6.09 ± 0.94 mm; iliac crest, 5.74 ± 0.88 mm). There was no significant difference in conformance between sides of graft harvest. CONCLUSIONS: When considering nonvascularized bone grafts for reconstruction of the orbital floor, both the scapula and iliac crest offer nearly complete conformance to the orbital floor structure and represent reasonable reconstructive options.

Determining Patient Preferences for Indeterminate Thyroid Nodules: Observation, Surgery or Molecular Tests.

BACKGROUND: Gene-expression classifiers (GEC) and genetic mutation panels (GMP) have been shown to improve preoperative diagnostic evaluations of indeterminate thyroid nodules. Despite the improvement, uncertainty regarding the proper management exists. Patient preferences may better inform the management of these indeterminate thyroid nodules. METHODS: Hypothetical scenarios were administered to two groups of patients: those with previous FNA-confirmed indeterminate thyroid nodules (Group A, n = 50) and those presenting to a general otolaryngology clinic for other reasons (Group B, n = 50). We evaluated patient preferences for surgery, observation and the use of molecular tests while varying the risk of malignancy, cost and diagnostic properties of the tests. RESULTS: The mean threshold for choosing surgery over observation was a 38.6% risk of malignancy on FNA. When offered either GEC, GMP or both (with their inherent imperfect diagnostic properties) in addition to the indeterminate FNA, 85.0% of respondents picked at least one of the molecular tests over either observation or surgery if the test(s) were free of charge. However, only 51.7% of respondents chose at least one of the tests when asked to pay the current cost of the test(s) (p < 0.001). On multivariable analysis, sex, the presence of an indeterminate FNA diagnosis and income level significantly predicted the desire to proceed with a molecular test above standard management. CONCLUSION: Patient preferences for thyroid nodule management are dependent on the risk of malignancy, prognosis of cancer and costs. Patients prefer molecular tests over standard management with indeterminate thyroid nodules, but the costs of the test(s) reduce the desire.

Recurrent genomic alterations in sequential progressive leukoplakia and oral cancer: drivers of oral tumorigenesis?

A significant proportion (up to 62%) of oral squamous cell carcinomas (OSCCs) may arise from oral potential malignant lesions (OPMLs), such as leukoplakia. Patient outcomes may thus be improved through detection of lesions at a risk for malignant transformation, by identifying and categorizing genetic changes in sequential, progressive OPMLs. We conducted array comparative genomic hybridization analysis of 25 sequential, progressive OPMLs and same-site OSCCs from five patients. Recurrent DNA copy number gains were identified on 1p in 20/25 cases (80%) with minimal, high-level amplification regions on 1p35 and 1p36. Other regions of gains were frequently observed: 11q13.4 (68%), 9q34.13 (64%), 21q22.3 (60%), 6p21 and 6q25 (56%) and 10q24, 19q13.2, 22q12, 5q31.2, 7p13, 10q24 and 14q22 (48%). DNA losses were observed in >20% of samples and mainly detected on 5q31.2 (35%), 16p13.2 (30%), 9q33.1 and 9q33.29 (25%) and 17q11.2, 3p26.2, 18q21.1, 4q34.1 and 8p23.2 (20%). Such copy number alterations (CNAs) were mapped in all grades of dysplasia that progressed, and their corresponding OSCCs, in 70% of patients, indicating that these CNAs may be associated with disease progression. Amplified genes mapping within recurrent CNAs (KHDRBS1, PARP1, RAB1A, HBEGF, PAIP2, BTBD7) were selected for validation, by quantitative real-time PCR, in an independent set of 32 progressive leukoplakia, 32 OSSCs and 21 non-progressive leukoplakia samples. Amplification of BTBD7, KHDRBS1, PARP1 and RAB1A was exclusively detected in progressive leukoplakia and corresponding OSCC. BTBD7, KHDRBS1, PARP1 and RAB1A may be associated with OSCC progression. Protein-protein interaction networks were created to identify possible pathways associated with OSCC progression.

Persistent, severe post-thrombolysis angioedema: Simple management of a difficult problem.

Post-thrombolysis orolingual angioedema in the setting of managing acute stroke is reported in the literature as most often being mild and self-limiting. We present a case of severe angioedema resulting in persistent macroglossia, representing a different end of the spectrum of disease than that referenced in the literature. Despite the severity of the tongue edema in our case, it did resolve with a relatively simple intervention. In addition to highlighting that post-thrombolysis angioedema can be potentially life threatening, this report reviews the pathophysiology of this condition and discusses management options for macroglossia in this setting.

Facial nerve reconstruction and facial disfigurement after radical parotidectomy.

BACKGROUND: The importance of facial contouring with facial nerve reconstruction following total and radical parotidectomy is often overlooked. The goal of this study was to quantify the level of facial disfigurement and nerve dysfunction following reconstruction of the facial nerve, with or without reconstruction of the contours, using free tissue transfer. METHODS: A total of 26 patients with radical parotidectomy and facial nerve reconstruction were included in this retrospective study. Of the 26 patients, 15 underwent follow-up interviews and evaluation of facial nerve function and disfigurement using three different scales: the regional House-Brackmann (H-B) scale, the Facial Clinimetric Evaluation (FaCE) Scale, and the observer-rated disfigurement scale. RESULTS: Of the 15 evaluated patients, 8 patients underwent free tissue transfer. Mean follow-up time was 39 months (median, 35; range, 11-65 months). Of the 15 patients, 10 patients had good or moderate function according to the H-B mouth scale (median score, 4; range, 2-5), and satisfactory eye closure was observed in 10 patients (median score, 3; range, 2-5). The mean disfigurement value rated by the physician was 5 (scale, 1-9), with a mean patient rating of 4. Subjective total FaCE score varied significantly (mean, 52; range, 13-93). CONCLUSIONS: Facial nerve and soft tissue reconstruction are highly beneficial to patients undergoing radical parotidectomy.

Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin.

Polymorphous low-grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of minor salivary gland (CAMSG) are low-grade carcinomas arising most often in oral cavity and oropharynx, respectively. Controversy exists as to whether these tumors represent separate entities or variants of one spectrum, as they appear to have significant overlap, but also clinicopathologic differences. As many salivary carcinomas harbor recurrent translocations, paired-end RNA sequencing and FusionSeq data analysis was applied for novel fusion discovery on two CAMSGs and two PLGAs. Validated rearrangements were then screened by fluorescence in situ hybridization (FISH) in 60 cases. Histologic classification was performed without knowledge of fusion status and included: 21 CAMSG, 18 classic PLGA, and 21 with "mixed/indeterminate" features. The RNAseq of 2 CAMSGs showed ARID1A-PRKD1 and DDX3X-PRKD1 fusions, respectively, while no fusion candidates were identified in two PLGAs. FISH for PRKD1 rearrangements identified 11 additional cases (22%), two more showing ARID1A-PRKD1 fusions. As PRKD2 and PRKD3 share similar functions with PRKD1 in the diacylglycerol and protein kinase C signal transduction pathway, we expanded the investigation for these genes by FISH. Six additional cases each showed PRKD2 and PRKD3 rearrangements. Of the 26 (43%) fusion-positive tumors, there were 16 (80%) CAMSGs and 9 (45%) indeterminate cases. A PRKD2 rearrangement was detected in one PLGA (6%). We describe novel and recurrent gene rearrangements in PRKD1-3 primarily in CAMSG, suggesting a possible pathogenetic dichotomy from "classic" PLGA. However, the presence of similar genetic findings in half of the indeterminate cases and a single PLGA suggests a possible shared pathogenesis for these tumor types.

Vertical Partial Laryngectomy With Temporoparietal Free-Flap Reconstruction for Recurrent Laryngeal Cancer: Long-Term Study.

Objective: Treatment options for recurrent early glottic carcinoma's include conservative and radical surgical options. These options offer similar survival benefits with different impacts of patient's quality of life. We previously present our experience with vertical partial laryngectomy (VPL) and showed high locoregional control rates with high-quality voice results and normal swallowing. Study Design: A long-term retrospective review. Setting: Tertiary Care Center. Methods: We analyzed all patients underwent VPL between the years 1995 to 2018. Long-term oncologic and functional outcomes were collected. Results: A total of 40 patients were included. The majority of whom were male (n = 38, 95%) with a mean age of 64.9 years (SD ± 9.5). With a median follow up time of 12 years (range 0-24), 9 patients (22.5%) had disease recurrence; the majority of whom (8 patients), had local recurrence and all were salvaged with total laryngectomy. Eight patients (20%) developed second primaries in the head and neck region with a median time to diagnosis of 77 months (range 8-227 months). Ten-years overall survival, disease specific survival, and local disease-free survival were 80%, 90%, and 80%, respectively. Five patients had postoperative laryngeal dysfunction with a total 10-years laryngectomy free survival of 70%. Conclusion: VPL has a sustainable oncologic outcome with a high long-term laryngectomy free survival rate. This entity is an acceptable conservative salvage option for selected postradiated recurrent laryngeal squamous cell carcinoma patients.

A 3D Analysis of Plating Strategies in Mandibular Reconstruction: A Randomized Control Pilot Study.

OBJECTIVE(S): The purpose of this study was to compare computer-assisted mandibular plating to conventional plating using quantitative metrics. METHODS: Patients scheduled to undergo mandibular reconstruction were randomized to three-dimensional modelling for preoperative plate bending or intraoperative freehand bending. Preoperative and postoperative head and neck computed tomography scans were obtained to generate computer models of the reconstruction. The overall plate surface contact area, mean plate-to-bone distance, degree of conformance, and position of the condylar head within the glenoid fossa between pre- and post-operative scans were calculated. RESULTS: Twenty patients were included with a mean age of 57.8 years (standard deviation [SD] = 13.6). The mean follow-up time was 9.8 months (range = 1.6-22.3). Reconstruction was performed with fibular (25%) or scapular free flaps (75%). The percentage of surface contact between the reconstructive plate and mandible was improved with three-dimensional models compared to freehand bending (93.9 ± 7.7% vs. 78.0 ± 19.9%, p = 0.04). There was improved overall plate-to-bone distance (3D model: 0.7 ± 0.31 mm vs. conventional: 1.3 ± 0.8 mm, p = 0.06). Total intraoperative time was non-significantly decreased with the use of a model (3D model: 726.5 ± 89.1 min vs. conventional: 757.3 ± 84.1 min, p = 0.44). There were no differences in condylar head position or postoperative complications. CONCLUSION: Computer-assisted mandibular plating can be used to improve the accuracy of plate contouring. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:2182-2186, 2024.

Optimizing Osteotomy Geometries in Posterolateral Mandibulectomies.

Importance: Reconstructive stability after mandibulectomy with osseous autogenous transplant is influenced by masticatory forces and the resulting stress on the titanium plate. Objective: To determine an optimal geometry of mandibular osteotomy that minimizes undesirable loading of the reconstruction plate. Design, Setting, and Participants: In this combined in silico and in vitro basic science study, segmented computed tomography images of an adult male human mandible downloaded from the Visible Human Project were analyzed. Data were collected from July to November 2023. Exposures: Four posterolateral mandibular resections and bony transplants were modeled following (1) vertical, (2) angled, (3) step, and (4) sagittal osteotomies. Using SOLIDWORKS software, mastication was simulated under (1) incisal, (2) ipsilateral molar, and (3) contralateral molar loading. Mandible models were then 3-dimensionally printed, osteotomized, and plated. Masticatory loads were simulated using pulleys, and strains were measured using strain gauges. Main Outcomes and Measures: On the reconstruction plate, von Mises stresses were measured in silico, and strains were measured using strain gauges in vitro. Stress and strain are reactions of a material to loading that can result in irreversible deformation or fracture. Results: In silico, maximum plate stress was highest with the vertical osteotomy, followed by the angled osteotomy (median difference vs vertical: ipsilateral molar loading, 126 MPa; 95% CI, 18-172; incisal loading, -24 MPa; 95% CI, -89 to 31; contralateral molar loading, 91 MPa; 95% CI, 23-189), step osteotomy (median difference vs angled: ipsilateral molar loading, 168 MPa; 95% CI, 112-235; incisal loading, 80 MPa; 95% CI, 15-140; contralateral molar loading, -17; 95% CI, -115 to 83), and sagittal osteotomy (median difference vs step: ipsilateral molar loading, 122 MPa; 95% CI, 102-154; incisal loading, 197 MPa; 95% CI, 166-230; contralateral molar loading, 161 MPa; 95% CI, 21-232). An angled osteotomy had the lowest stress at 30° of angulation (median difference vs contralateral molar loading at 40° of angulation: 111 MPa; 95% CI, 4-186). In vitro, the vertical osteotomy had the highest maximum strain, followed by the angled osteotomy (mean difference vs vertical: incisal loading, 0.021 mV/V; 95% CI, 0.014-0.027; contralateral molar loading, 0 mV/V; 95% CI, -0.004 to 0.005), step osteotomy (mean difference vs angled: incisal loading, 0.015 mV/V; 95% CI, 0.003-0.028; contralateral molar loading, 0.021 mV/V; 95% CI, 0.016-0.027), and sagittal osteotomy (mean difference vs step: incisal loading, 0.006 mV/V; 95% CI, -0.006 to 0.018; contralateral molar loading, 0.020 mV/V; 95% CI, 0.015-0.026). Conclusions and Relevance: In this study, the traditional vertical osteotomy resulted in less favorable plate stresses in all loading scenarios compared with angled, step, or sagittal osteotomies, in silico and in vitro. Future clinical studies analyzing the impact of varying osteotomy geometries are warranted to translate these findings to the operating room.

Development of a Preclinical Double Model of Mandibular Irradiated Bone and Osteoradionecrosis in New Zealand Rabbits.

PURPOSE: Radiotherapy (RT) plays a crucial role in head and neck (HN) cancer treatment. Nevertheless, it can lead to serious and challenging adverse events such as osteoradionecrosis (ORN). A preclinical rabbit model of irradiated bone and ORN is herein proposed, with the aim to develop a viable model to be exploited for investigating new therapeutic approaches. METHODS: Nine New Zealand white rabbits were irradiated using a single beam positioned to the left of the mandible and directed perpendicular to the left mandible. A 10 × 10 mm2 region of interest (ROI) located below the first molar tooth on the left side was identified and irradiated with 7 Gy each fraction, once every 2 days, for five fractions. Dose distributions demonstrated that the corresponding ROI on the contralateral (right) mandibular side received approximately 5 Gy each fraction, thus bilateral irradiation of the mandible was achieved. ROIs were categorized as ROIH on the left side receiving the high dose and ROIL on the right side receiving the low dose. Rabbits were followed up clinically and imaged monthly. After 4 months, the irradiated bone was excised, and histological examination of ROIs was performed. RESULTS: Radiological signs suggestive for ORN were detected in the entire population (100%) 16 weeks after irradiation on ROIH, which consisted of cortical erosion and loss of trabeculae. ROIL did not show any radiological evidence of bone damage. Histologically, both sides showed comparable signs of injury, with marked reduction in osteocyte count and increase in empty lacunae count. CONCLUSIONS: A preclinical double model was successfully developed. The side receiving the higher dose showed radiological and histological signs of bone damage, resulting in an ORN model. Whereas the contralateral side, receiving the lower dose, presented with histological damage only and a normal radiological appearance. This work describes the creation of a double model, an ORN and irradiated bone model, for further study using this animal species.

Length of Stay Prediction Models for Oral Cancer Surgery: Machine Learning, Statistical and ACS-NSQIP.

OBJECTIVE: Accurate prediction of hospital length of stay (LOS) following surgical management of oral cavity cancer (OCC) may be associated with improved patient counseling, hospital resource utilization and cost. The objective of this study was to compare the performance of statistical models, a machine learning (ML) model, and The American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) calculator in predicting LOS following surgery for OCC. MATERIALS AND METHODS: A retrospective multicenter database study was performed at two major academic head and neck cancer centers. Patients with OCC who underwent major free flap reconstructive surgery between January 2008 and June 2019 surgery were selected. Data were pooled and split into training and validation datasets. Statistical and ML models were developed, and performance was evaluated by comparing predicted and actual LOS using correlation coefficient values and percent accuracy. RESULTS: Totally 837 patients were selected with mean patient age being 62.5 ± 11.7 [SD] years and 67% being male. The ML model demonstrated the best accuracy (validation correlation 0.48, 4-day accuracy 70%), compared with the statistical models: multivariate analysis (0.45, 67%) and least absolute shrinkage and selection operator (0.42, 70%). All were superior to the ACS-NSQIP calculator's performance (0.23, 59%). CONCLUSION: We developed statistical and ML models that predicted LOS following major free flap reconstructive surgery for OCC. Our models demonstrated superior predictive performance to the ACS-NSQIP calculator. The ML model identified several novel predictors of LOS. These models must be validated in other institutions before being used in clinical practice. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3664-3672, 2024.

Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical in vivo study with assessment of translationally relevant aspects.

Background: Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction. Methods: In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly ( ε -caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses. Results: The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs. The immunohistochemical profile showed significantly higher expression of both VEGF-A and osteopontin in defects reconstructed with scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group. Conclusion: Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.

Telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER): A pilot study for patients treated with surgery for oral cavity carcinoma.

BACKGROUND: To address the rehabilitative barriers to frequency and precision of care, we conducted a pilot study of a biofeedback electropalatography (EPG) device paired with telemedicine for patients who underwent primary surgery +/- adjuvant radiation for oral cavity carcinoma. We hypothesized that lingual optimization followed by telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER) would further improve speech and swallowing outcomes after "standard-of-care" SOC rehabilitation. METHOD: Pilot prospective 8-week (TEBER) program following 8 weeks of (SOC) rehabilitation. RESULTS: Twenty-seven patients were included and 11 completed the protocol. When examining the benefit of TEBER independent of standard of care, "range-of-liquids" improved by +0.36 [95% CI, 0.02-0.70, p = 0.05] and "range-of-solids" improved by +0.73 [95% CI, 0.12-1.34, p = 0.03]. There was a positive trend toward better oral cavity obliteration; residual volume decreased by -1.2 [95% CI, -2.45 to 0.053, p = 0.06], and "nutritional-mode" increased by +0.55 [95% CI, -0.15 to 1.24, p = 0.08]. CONCLUSION: This pilot suggests that TEBER bolsters oral rehabilitation after 8 weeks of SOC lingual range of motion.

Association of two BRM promoter polymorphisms with head and neck squamous cell carcinoma risk.

The SWI/SNF chromatin remodeling complex is an important regulator of gene expression that has been linked to cancer development. Expression of Brahma (BRM), a critical catalytic subunit of SWI/SNF, is lost in a variety of solid tumors. Two novel BRM promoter polymorphisms (BRM-741 and BRM-1321) have been correlated with BRM loss and elevated cancer risk. The aim(s) of this study were to examine BRM expression in head and neck squamous cell carcinoma (HNSCC) and to correlate BRM polymorphisms with HNSCC risk. BRM expression studies were performed on eight HNSCC cell lines and 76 surgically resected tumor samples. A case-control study was conducted on 668 HNSCC patients (oral cavity, oropharynx, larynx and hypopharynx) and 700 healthy matched controls. BRM expression was lost in 25% of cell lines and 16% of tumors. The homozygous genotype of each polymorphism was significantly associated with increased HNSCC risk [BRM-741: adjusted odds ratio (aOR) 1.75, 95% CI 1.2-2.3, P < 0.001; BRM-1321: aOR 1.65, 95% CI 1.2-2.2, P < 0.001]. Individuals that were homozygous for both BRM polymorphisms had a more than 2-fold increase in the risk of HNSCC (aOR 2.23, 95% CI 1.5-3.4, P < 0.001). A particularly elevated risk was seen within the oropharynx, human papillomavirus-positive subgroup for carriers of both homozygous variants (aOR 3.09, 95% CI 1.5-6.8, P = 0.004). BRM promoter polymorphisms appear to act as susceptibility markers of HNSCC with potential utility in screening, prevention and treatment.

Social environment, secondary smoking exposure, and smoking cessation among head and neck cancer patients.

BACKGROUND: Smoking during treatment of squamous cell head and neck cancer (HNC) has adverse affects on toxicity, treatment, and survival. The purpose of this report was to evaluate sociodemographic predictors of smoking cessation in HNC patients to support the development of a smoking cessation program. METHODS: Newly diagnosed HNC patients (2007-2010) at Princess Margaret Cancer Centre treated with curative intent were prospectively recruited. Patients completed self-reported baseline and follow-up questionnaires, assessing changes in social habits. Predictors of smoking cessation and time to quitting were evaluated using logistic regression and Cox proportional hazard models, respectively. RESULTS: Of 295 HNC patients, 49% were current smokers at diagnosis, and 50% quit after diagnosis. These individuals were more likely to have smoked for fewer years (P = .0003), never used other forms of tobacco (P = .0003), and consumed less alcohol (P = .002). No cigarette exposure at home (OR, 7.44 [3.04-18.2]), no spousal smoking (OR, 4.25 [1.70-10.6]), and having fewer friends who smoke (OR, 2.32 [1.00-5.37]) were consistent predictors of smoking cessation after diagnosis. Having none of these exposures (OR, 13.8 [4.13-46.0]) and seeing a family physician (OR, 3.92 [1.38-11.2]) were independently associated with smoking cessation and time-to-quitting analyses. Most HNC patients (68%) quit within 6 months of diagnosis. Patients who were ex-smokers at diagnosis were older (P < .0001), more likely to be female (P = .0002), more likely to be married (P = .0004), more educated (P = .01), and had fewer pack-years of smoking (P < .0001). CONCLUSIONS: Spousal smoking, peer smoking, smoke exposure at home, and seeing a family physician were strongly and consistently associated with smoking cessation and time to quitting after a HNC diagnosis.