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.

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.

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.

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.

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.

Union and bone resorption of free fibular flaps in mandibular reconstruction.

BACKGROUND: The purpose of this study was to evaluate bony union and resorption after free fibular flap reconstruction for mandibular reconstruction. METHODS: A total of 112 patients with composite resection and reconstruction with a fibular free flap were included. Computed tomography scan images taken after the reconstruction and approximately 1 year postoperatively were assessed to evaluate union (n = 60) and bone resorption (n = 24) of the neomandible. RESULTS: Most of the fibulas healed well (n = 34) and there was radiologic nonunion in 20% of the neomandibles at the time of evaluation (mean = 15 months). There was a statistically significant reduction in bone height in the native mandible (p = 0.02) and the anterior part of the fibular graft (p = 0.02). CONCLUSIONS: There was a statistically significant reduction in mandibular and fibular graft height. However, the bone resorption was clinically minimal. Sufficient maintenance of height and good bony union support the use of free fibular flap in mandibular reconstruction.

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.

Projected cutting guides using an augmented reality system to improve surgical margins in maxillectomies: A preclinical study.

BACKGROUND: Positive margins have been reported up to 80% in advanced maxillary cancers. Intraoperative navigation (IN) aims to improve margins, but provides a two-dimensional view of a registered instrument without anticipating any cutting directions, and the information is displayed in monitors outside surgical field. Augmented Reality (AR) can delineate margins while addressing the gaze-toggling drawback of IN. In a preclinical setting, we implemented preoperative-planned osteotomies needed for maxillectomies and projected this information on the surgical field using AR. We aimed to improve negative margin rates while retaining the benefits of AR. METHODS: Five maxillary tumor models were built. Five fellowship-trained surgeons completed virtual unguided and AR-guided maxillectomies. Comparisons in terms of intratumoral cuts, close, adequate, and excessive distances from the tumor were performed. Differences between "ideal" cutting-plan and the AR-guided virtual osteotomies was obtained. Workload questionnaires to evaluate the technology were completed. RESULTS: 115 virtual osteotomies were analyzed. Intra-tumoral and "close" margins were lower for the AR-assisted osteotomies (0.0% vs 1.9% p < 0.0001 and 0.8% vs 7.9% p < 0.0001). Proportion of "adequate" margins were higher in the AR simulations (25.3% vs 18.6%, p = 0.018). The AR osteotomies had high similarity with the pre-planned with interclass correlation index close to 1 in "adequate" margins 0.893 (95% CI: 0.804-0.949). Workload scores were better for AR-guided simulations for the domains of mental demand, performance, effort and frustration. CONCLUSION: The projector-based AR method improved margin delineation, and preoperative planning was accurately translated to the simulations. Clinical translation will aim to consolidate our preclinical findings to improve outcomes.

The MUSES∗: a prognostic study on 1360 patients with sinonasal cancer undergoing endoscopic surgery-based treatment: ∗MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

BACKGROUND: Over the last 2 decades, transnasal endoscopic surgery (TES) has become the most frequently employed surgical technique to treat sinonasal malignancies. The rarity and heterogeneity of sinonasal cancers have hampered large non-population-based analyses. METHODOLOGY: All patients receiving TES-including treatment between 1995 and 2021 in 5 referral hospitals were included. A prognostic study was performed, and multivariable models were transformed into nomograms. Training and validation sets were based on results from 3 European and 2 non-European centres, respectively. RESULTS: The training and validation set included 940 and 420 patients, respectively. The mean age at surgery, primary-versus-recurrent presentation, histology distribution, type of surgery, T category and type of adjuvant treatment were differently distributed in the training and validation set. In the training set, 5-year overall survival and recurrence-free survival with a 95%-confidence interval were 72.7% (69.5-76.0%) and 66.4% (63.1-69.8%), respectively, significantly varying with histology. At multivariable analyses, age, gender, previous treatment, the extent of resection on the cranial, lateral and posterolateral axes, grade/subtype, T category, nodal status, margin status and adjuvant treatment were all associated with different prognostic outcomes, displaying a heterogeneous significance and effect size according to histology. The internal and external validation of nomograms was satisfactory (optimism-corrected C-index >0.7 and cumulative area under curve >0.7) for all histologies but mucosal melanoma. CONCLUSIONS: Outcomes of TES-based treatment of sinonasal cancers vary substantially with histology. This large, non-population-based study provides benchmark data on the prognosis of sinonasal cancers that are deemed suitable for treatment including TES.

Frequent malpositions of peripherally inserted central venous catheters in patients undergoing head and neck surgery.

PURPOSE: Peripherally inserted central venous catheters (PICCs) do not interfere with surgical access during neck dissection and are used in patients undergoing head and neck surgery. However, severe complications associated with malpositioning of PICCs have been reported in these patients. We conducted a retrospective study to determine the incidence of aberrant positioning of PICCs in patients undergoing free flap reconstructive (FFR) surgery for head and neck malignancies. METHODS: We analyzed a database of 269 patients undergoing FFR surgery. After induction of general anesthesia, a PICC was inserted successfully in 130 patients (48%) at bedside without image guidance. A PICC was not used in 139 patients (52%). A chest x-ray was performed at admission to the postanesthetic care unit, stored digitally, and reviewed retrospectively by two independent observers. Based on the chest x-ray findings, the PICC position was classified as proper, suboptimal, or aberrant and defined according to the position of the PICC tip, i.e., proper, if situated in the ipsilateral innominate vein or in the superior vena cava; suboptimal, if situated in the subclavian vein; and aberrant, if situated in any other location. RESULTS: Proper, suboptimal, and aberrant PICC positions were found in 68 (52%), 17 (13%), and 45 (35%) patients, respectively. The proper position was confirmed more frequently with a left- than with a right-sided approach: 23/29 (79%) vs 45/101 (44%) patients, respectively (P < 0.001). CONCLUSIONS: There is a high incidence of aberrant positioning when PICCs are inserted without image guidance. The left-sided approach might be preferable due to a lower incidence of malpositions. The risk-benefit ratio should be estimated carefully before using a PICC in patients undergoing FFR procedures.

Objective evaluation of orbito-zygomatic reconstruction with scapular tip free flaps to restore facial projection and orbital volume.

BACKGROUND: Restoring anatomical contour and position of the malar eminence and orbital rim following ablative mid-face procedures is critical in maintaining facial contour and orbit position. OBJECTIVE: To report our reconstructive approach using the scapular tip free-flap (STFF) for orbito-zygomatic defects, evaluating contour and overall shape restoration. METHODS: The study included 2 series: a clinical cohort of 15 consecutive patients who underwent an orbito-zygomatic reconstruction with a STFF and a cohort of 10 patients who had CT scan imaging but did not have orbito-zygomatic surgical resection or reconstruction. Using a 3D software, overall conformance (OC) and contour conformance (CC) with respect to the mirrored contralateral (clinical cohort) or native zygoma (preclinical cohort) were analyzed. Postoperative orbital volumes were also measured in the clinical cohort. Mean, median, root-mean-square (RMS), minimum and maximum measurements were obtained both for OC and CC. Conformance values of clinical and preclinical cohort were compared to objectively evaluate the quality of reconstruction in terms of orbito-zygomatic framework restoration (Mann-Whitney test). RESULTS: All measurements for OC and CC between scapular tip and the zygoma showed no differences, both on the clinical (RMS: OC 3.29 mm vs CC 3.32 mm -p = NS-) and preclinical (RMS: OC 2.03 mm and CC 2.31 mm -p = NS-) cohorts. Moreover, there were no differences in post-operative orbital volumes in the clinical cohort. Clinical outcomes of the case-series are also reported. CONCLUSION: The STFF is highly effective in restoring facial projection and orbital volume in orbito-zygomatic reconstruction.

Regional Recurrences and Hyams Grade in Esthesioneuroblastoma.

Objective The aim of this study is to determine if Hyams grade may help predict which patients with esthesioneuroblastoma (ENB) tumors are likely to develop regional recurrences, and to determine the impact of tumor extent on regional failure in ENB patients without evidence of nodal disease at presentation. Design The study was designed as a retrospective review for ENB patients. Settings The study was prepared at tertiary care academic center for ENB patients. Participants Patients with ENB were included in the study. Main Outcome Measures Oncologic outcomes (5-year regional and locoregional control (LRC) and overall survival) in patients with Hyams low grade versus high grade. Oncologic outcomes based on radiographic disease extent. Results A total of 43 patients were included. Total 25 patients (58%) had Hyams low-grade tumor, and 18 (42%) had high-grade tumor. Of the 34 patients without regional disease at presentation, 8 (24%) were treated with elective nodal radiation. There were no statistically significant differences in 5-year regional control in the Hyams low-grade versus high-grade groups (78 vs. 89%; p = 0.4). The 5-year LRC rates in patients with low grade versus high grade were 73 versus 89% ( p = 0.6). The 5-year overall survival rates in patients with low-grade versus high-grade tumors were 86 versus 63% ( p = 0.1). Radiographic extension of disease into the olfactory groove, olfactory nerve, dura, and periorbita were statistically associated with decreased 5-year overall survival (5-year OS 49 vs. 91% [ p = 0.04], 49 vs. 91% [ p = 0.04], 44 vs. 92% [ p = 0.02], and 44 vs. 80% [ p = 0.04], respectively). Conclusion ENBs are associated with a risk of regional failure. The current analysis suggests that Hyams low-grade and high-grade malignancies have comparable rates of early and delayed regional recurrences, although small sample size may limit our conclusions.

Augmented Reality and Intraoperative Navigation in Sinonasal Malignancies: A Preclinical Study.

OBJECTIVE: To report the first use of a novel projected augmented reality (AR) system in open sinonasal tumor resections in preclinical models and to compare the AR approach with an advanced intraoperative navigation (IN) system. METHODS: Four tumor models were created. Five head and neck surgeons participated in the study performing virtual osteotomies. Unguided, AR, IN, and AR + IN simulations were performed. Statistical comparisons between approaches were obtained. Intratumoral cut rate was the main outcome. The groups were also compared in terms of percentage of intratumoral, close, adequate, and excessive distances from the tumor. Information on a wearable gaze tracker headset and NASA Task Load Index questionnaire results were analyzed as well. RESULTS: A total of 335 cuts were simulated. Intratumoral cuts were observed in 20.7%, 9.4%, 1.2,% and 0% of the unguided, AR, IN, and AR + IN simulations, respectively (p < 0.0001). The AR was superior than the unguided approach in univariate and multivariate models. The percentage of time looking at the screen during the procedures was 55.5% for the unguided approaches and 0%, 78.5%, and 61.8% in AR, IN, and AR + IN, respectively (p < 0.001). The combined approach significantly reduced the screen time compared with the IN procedure alone. CONCLUSION: We reported the use of a novel AR system for oncological resections in open sinonasal approaches, with improved margin delineation compared with unguided techniques. AR improved the gaze-toggling drawback of IN. Further refinements of the AR system are needed before translating our experience to clinical practice.

Navigation-Guided Transnasal Endoscopic Delineation of the Posterior Margin for Maxillary Sinus Cancers: A Preclinical Study.

BACKGROUND: The resection of advanced maxillary sinus cancers can be challenging due to the anatomical proximity to surrounding critical anatomical structures. Transnasal endoscopy can effectively aid the delineation of the posterior margin of resection. Implementation with 3D-rendered surgical navigation with virtual endoscopy (3D-SNVE) may represent a step forward. This study aimed to demonstrate and quantify the benefits of this technology. MATERIAL AND METHOD: Four maxillary tumor models with critical posterior extension were created in four artificial skulls (Sawbones®). Images were acquired with cone-beam computed tomography and the tumor and carotid were contoured. Eight head and neck surgeons were recruited for the simulations. Surgeons delineated the posterior margin of resection through a transnasal approach and avoided the carotid while establishing an adequate resection margin with respect to tumor extirpation. Three simulations were performed: 1) unguided: based on a pre-simulation study of cross-sectional imaging; 2) tumor-guided: guided by real-time tool tracking with 3D tumor and carotid rendering; 3) carotid-guided: tumor-guided with a 2-mm alert cloud surrounding the carotid. Distances of the planes from the carotid and tumor were classified as follows and the points of the plane were classified accordingly: "red": through the carotid artery; "orange": <2 mm from the carotid; "yellow": >2 mm from the carotid and within the tumor or <5 mm from the tumor; "green": >2 mm from the carotid and 5-10 mm from the tumor; and "blue": >2 mm from the carotid and >10 mm from the tumor. The three techniques (unguided, tumor-guided, and carotid-guided) were compared. RESULTS: 3D-SNVE for the transnasal delineation of the posterior margin in maxillary tumor models significantly improved the rate of margin-negative clearance around the tumor and reduced damage to the carotid artery. "Green" cuts occurred in 52.4% in the unguided setting versus 62.1% and 64.9% in the tumor- and carotid-guided settings, respectively (p < 0.0001). "Red" cuts occurred 6.7% of the time in the unguided setting versus 0.9% and 1.0% in the tumor- and carotid-guided settings, respectively (p < 0.0001). CONCLUSIONS: This preclinical study has demonstrated that 3D-SNVE provides a substantial improvement of the posterior margin delineation in terms of safety and oncological adequacy. Translation into the clinical setting, with a meticulous assessment of the oncological outcomes, will be the proposed next step.

Programmed cell death 4 loss increases tumor cell invasion and is regulated by miR-21 in oral squamous cell carcinoma.

BACKGROUND: The tumor suppressor Programmed Cell Death 4 (PDCD4) has been found to be under-expressed in several cancers and associated with disease progression and metastasis. There are no current studies characterizing PDCD4 expression and its clinical relevance in Oral Squamous Cell Carcinoma (OSCC). Since nodal metastasis is a major prognostic factor in OSCC, we focused on determining whether PDCD4 under-expression was associated with patient nodal status and had functional relevance in OSCC invasion. We also examined PDCD4 regulation by microRNA 21 (miR-21) in OSCC. RESULTS: PDCD4 mRNA expression levels were assessed in 50 OSCCs and 25 normal oral tissues. PDCD4 was under-expressed in 43/50 (86%) OSCCs, with significantly reduced mRNA levels in patients with nodal metastasis (p = 0.0027), and marginally associated with T3-T4 tumor stage (p = 0.054). PDCD4 protein expression was assessed, by immunohistochemistry (IHC), in 28/50 OSCCs and adjacent normal tissues; PDCD4 protein was absent/under-expressed in 25/28 (89%) OSCCs, and marginally associated with nodal metastasis (p = 0.059). A matrigel invasion assay showed that PDCD4 expression suppressed invasion, and siRNA-mediated PDCD4 loss was associated with increased invasive potential of oral carcinoma cells. Furthermore, we showed that miR-21 levels were increased in PDCD4-negative tumors, and that PDCD4 expression may be down-regulated in OSCC by direct binding of miR-21 to the 3'UTR PDCD4 mRNA. CONCLUSIONS: Our data show an association between the loss of PDCD4 expression, tumorigenesis and invasion in OSCC, and also identify a mechanism of PDCD4 down-regulation by microRNA-21 in oral carcinoma. PDCD4 association with nodal metastasis and invasion suggests that PDCD4 may be a clinically relevant biomarker with prognostic value in OSCC.