Janus, Jeffrey R.

Craniofacial reconstruction of critical bone defects typically requires a bone graft. As graft availability may be restricted by disease or comorbidities, tissue engineering approaches are actively sought. The pericranium could provide new bone graft material. During development and repair, bone transitions through a chondrogenic phase. However, with tissue engineering, pluripotent cells can differentiate directly into bone cells. Does ability to recapitulate bone formation in vitro affect osteogenesis and vascularization of pericranium grafts? To answer this, we obtained tissue from nine patients with preplanned craniotomy surgery and studied three-dimensional osteogenesis and angiogenesis of pericranium-derived spheroids. First, we established growth and differentiation conditions on Matrigel. For each spheroid sample, we investigated (i) continuous osteogenic differentiation (COD) and (ii) osteogenic differentiation preceded by chondrogenesis (CD → OD). The effect of vascular endothelial growth factor (VEGF) was compared to VEGF supplemented with fibroblast growth factor, interleukin (IL)-1, IL-6, platelet-derived growth factor, and tumor necrosis factor-α, a growth factor mix (GFM) with possible synergistic effects. In this limited sample, we observed no age- or sex-related differences in cell expansion. Similarly, no statistically significant differences in osteogenic or angiogenic scores between COD or CD → OD spheroids were noted with regular media. In COD, however, VEGF statistically significantly increased angiogenesis compared to control media ( p = 0.007). Also, in COD, both VEGF and VEGF + GFM increased osteogenesis ( p = 0.047 and p = 0.038, respectively). By contrast, in CD → OD, neither VEGF nor VEGF + GFM yielded statistically significant angiogenesis or osteogenesis scores compared to control media. To understand these results, we characterized spheroid protein expression by nanoliquid chromatography coupled to tandem mass spectrometry. Nine angiogenic proteins were either uniquely expressed or upregulated in COD compared to CD → OD: (i) endothelial markers JUP, PTGIS, PTGS2, and TYMP, (ii) tissue remodeling factors CHI3L1 and MMP14, and (iii) metabolic pathways modulators ANGPTL4, ITGA5, and WNT5A. ANGPTL4, ITGA5, PTGIS, PTGS2, and WNT5A define a conserved angiogenic network and were >2-fold increased in VEGF compared to VEGF + GFM. Finally, we examined bone formation on printable poly-(propylene-fumarate) (PPF) scaffolds for individualized grafting. Under COD + VEGF conditions, PPF scaffolds loaded with pericranium-derived cells displayed hallmarks of spongiform-like bone formation. Thus, the human pericranium may be a potential repository for bone-generating cells with applications in craniofacial bone repair using tissue printing.

AbstractBackgroundBuccal squamous cell carcinoma (SCC) is a locoregionally aggressive malignancy, representing a small subset of oral cancers in North America. We investigated the prognostic value of several clinicopathologic factors in a cohort of patients diagnosed with buccal SCC.MethodsBetween years 1992 and 2017, 52 patients were diagnosed with conventional buccal SCC. Archival surgical pathology material was retrospectively reviewed for reportable findings according to the latest reporting guidelines published by the College of American Pathologists. Clinical data were obtained through chart review.ResultsThe majority of patients were of older age, current or past smokers, and without specific gender predilection. Most presented at a clinically advanced stage and were treated with surgery alone, or surgery followed by adjuvant radiotherapy. The tumor recurred in about 40% of patients, and almost half of the patients died from the disease by the end of the follow‐up period. The worst pattern of invasion (WPOI) was associated with greater depth of invasion (DOI) (P = .031) and perineural invasion (P < .001). In univariate analyses, older age (P = .004), positive nodal status (P = .047), lymphovascular invasion (P = .012), perineural invasion (P = .05), and WPOI‐5 (P = .015) were adverse predictors of 5‐year overall survival (OS). In multivariate analysis, older age (P = .011), WPOI‐5 (P < .001), and perineural invasion (P = .001) remained statistically significant independent prognosticators of worse 5‐year OS.ConclusionsOlder age, WPOI‐5, and perineural invasion are significant prognosticators of worse OS. WPOI is associated with DOI, a finding which may have important implications for the pathogenesis and biologic behavior of the disease.

ObjectivesTo describe pain experience and opioid use after major head and neck reconstructive surgery.Study DesignRetrospective cohort study.MethodsPatients undergoing major head and neck surgery with microvascular free tissue transfer (free flaps) at a tertiary academic center were included. Pain scores (0–10) and demographic and clinical data were ascertained from medical records. Discharge opioid prescriptions and refills obtained within 30 days were recorded. Patient characteristics were compared with pain scores using nonparametric rank‐sum tests and with likelihood of refill using logistic regression models to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs).ResultsThe study population comprised 445 patients. Median age was 60 years (interquartile range 50–68). Most patients had cancer (N = 350, 78%). The majority of free flaps were fibula (N = 153, 34%) or radial forearm (N = 159, 36%). Older patients reported significantly lower pain scores, whereas patients with opioid tolerance, anxiety, current smokers, and those undergoing larger volume resections or boney free flaps reported significantly higher pain scores. One‐quarter (N = 115, 26%) of patients obtained opioid refills. Patients aged ≥ 60 years had one‐half the odds of obtaining a refill compared with patients aged < 60 years (adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.33–0.84), whereas surgical defect volume ≥ 100 cm3 (aOR = 1.92, 95% CI = 1.21–3.07) and higher pain score (aOR = 1.19, 95% CI = 1.07–1.32 per 1 point increase) increased the odds of refill.ConclusionContinued opioid use after discharge is common among patients undergoing major head and neck reconstruction, particularly for younger patients and after more extensive surgery. Older patients reported lower pain intensity and were less likely to obtain opioid refills, highlighting the wisdom of judicious opioid use for this vulnerable population.Level of EvidenceIV Laryngoscope, 130: E469–E478, 2020

IntroductionPatients who become severely ill from coronavirus disease 2019 (COVID‐19) have a high likelihood of needing prolonged intubation, making tracheostomy a likely consideration. The infectious nature of COVID‐19 poses an additional risk of transmission to healthcare workers that should be taken into consideration.MethodsWe explore current literature and recommendations for tracheostomy in patients with COVID‐19 and look back at previous data from severe acute respiratory syndrome coronavirus 1 (SARS‐CoV‐1), the virus responsible for the SARS outbreak of 2003.ResultsGiven the severity and clinical uncertainty of patients with COVID‐19 and the increased risk of transmission to clinicians, careful consideration should be taken prior to performing tracheostomy. If tracheostomy is performed, we recommend a bedside approach to limit exposure time and number of exposed personnel. Bronchoscopy use with a percutaneous approach should be limited in order to decrease viral exposure.ConclusionThorough preprocedural planning, use of experienced personnel, enhanced personal protective equipment where available, and a thoughtful anesthesia approach are instrumental in maximizing positive patient outcomes while successfully protecting the safety of healthcare personnel. Laryngoscope, 130:2546–2549, 2020

ObjectivesClinical variables affecting anesthetic recovery following transoral robotic surgery (TORS) to resect oropharyngeal squamous cell carcinoma have not been described. We aimed to explore risk factors associated with prolonged postanesthesia recovery following TORS.Study DesignRetrospective case‐control study.SettingTertiary referral center, January 2010 to November 2016.Subjects and MethodsPatients included adults undergoing primary TORS ± neck dissection for oropharyngeal squamous cell carcinoma. Patients were categorized by phase I recovery time into the “goal” recovery group (75th percentile [lower 3 quartiles], n = 272) and the “prolonged” recovery group (n = 91). Univariate and multivariate logistic regression analyses were performed to assess the associations between clinical characteristics and prolonged phase I recovery.ResultsA total of 363 patients were included. Median (interquartile range) duration of postanesthesia recovery was 1.5 hours (1.0‐2.0). Prolonged recovery was associated with isoflurane (odds ratio, 2.83 [95% CI, 1.56‐5.14], P <. 001), midazolam (2.77 [1.50‐5.12], P =. 001), and larger opioid doses (1.26 [1.01‐1.58] per 10‐mg intravenous morphine equivalents, P =. 040) and inversely associated with multimodal antiemetic therapy (0.34 [0.15‐0.78], P =. 011). Prolonged cases had higher rates of postoperative nausea and vomiting (n = 43 [47.2%] vs 86 [31.6%], P =. 008), respiratory depression (28 [30.8%] vs 12 [4.4%], P <. 001), sedation (Richmond Agitation‐Sedation Scale < –2; 26 [28.6%] vs 35 [12.9%], P =. 001), severe pain (numeric rating score ≥7; 31 [34.4%] vs 45 [17.2%], P =. 001), and longer hospital stays (4 vs 3 days, P <. 001).ConclusionsSeveral anesthetic factors are associated with anesthesia recovery duration, which may be shortened by efforts to reduce postoperative sedation, severe pain, and nausea/vomiting. Shortened anesthesia recovery time may reduce hospital stay.

Abstract Background Consensus in timing of radiotherapy is yet to be established in esthesioneuroblastoma (ENB). Objective This study was aimed to investigate if planned adjuvant radiotherapy improves tumor control after complete margin negative resection of low Hyams' grade (1 or 2) ENB. Methods A retrospective review of patients with pathologically confirmed negative margin resection of Kadish's stage B or C and Hyams' grade 1 and 2 ENBs was conducted. Seventeen patients meeting the criteria were divided into the following two groups for cohort study: (1) those who underwent planned immediate postoperative adjuvant radiotherapy (IR group) and (2) those who did not (delayed radiotherapy [DR] group). Results The IR group included nine patients (Kadish's stage B in one and stage C in eight; Hyams' grade 1 in two and grade 2 in seven). Mean follow-up was 140.8 months. Seven patients (78%) had disease progression (DP) at a median of 88 months (four with cervical lymph node metastasis [CLNM], one with distant metastasis, and two with both local recurrence and CLNM). One patient experienced frontal lobe abscess. The DR group included eight patients (Kadish's stage B in six and stage C in two; all Hyams' grade 2). Mean follow-up was 123.3 months. Four (50%) patients who developed DP (all local recurrence) were salvaged with surgery and adjuvant radiotherapy at a median of 37.5 months. There was no statistically significant difference in DP rate (p = 0.23), time to DP (p = 0.26), or the local tumor control rate (p = 0.23). Conclusion In our limited cohort, immediate postoperative radiotherapy did not demonstrate superiority in tumor control, although risk of radiotherapy toxicity appears low.

AbstractObjective The objective of this study is to describe the clinical presentation, tumor characteristics, natural history, and treatment patterns of sinonasal osteosarcoma.Methods Fourteen patients who had been treated for osteosarcoma of the nasal cavity and paranasal sinuses at a tertiary care center were reviewed. In addition, a systematic review of the literature for osteosarcoma of the sinonasal cavity was performed.Results In a systematic review, including 14 patients from the authors' institution, 53 total studies including 88 patients were assessed. Median follow-up was 18 months (interquartile range: 8–39 months). The most common presenting symptoms were facial mass or swelling (34%), and nasal obstruction (30%). The most common paranasal sinus involved by tumor was the maxillary sinus (64%), followed by the ethmoid sinuses (52%). The orbit (33%), dura (13%) and infratemporal fossa (10%) were the most common sites of local invasion. The majority of patients underwent surgery followed by adjuvant therapy (52.4%). Increasing age was associated with decreased overall survival rate (unit risk ratio [95% confidence interval (CI)] = 1.02 [1.003–1.043]; p = 0.0216) and T4 disease was associated with decreased disease-specific survival rate (hazard ratio [HR] = 2.87; p = 0.0495). The 2- and 5-year overall survival rates were 68 and 40%, respectively, while 2- and 5-year disease-specific survival rates were 71% and 44%, respectively.Conclusion Sinonasal osteosarcomas are uncommon tumors and can pose a significant therapeutic challenge. Increasing age and T4 disease are associated with worse prognosis. This disease usually warrants consultation by a multidisciplinary team and consideration of multimodality therapy.

AbstractEsthesioneuroblastoma (ENB) is a rare olfactory malignancy that can present with locally advanced disease. At our institution, patients with ENB in whom the treating surgeon believes that a margin-negative resection is initially not achievable are selected to undergo induction with chemotherapy with or without radiotherapy prior to surgery. In a retrospective review of 61 patient records, we identified six patients (10%) treated with this approach. Five of six patients (83%) went on to definitive surgery. Prior to surgery, three of five patients (60%) had a partial response after induction therapy, whereas two of five (40%) had stable disease. Microscopically margin-negative resection was achieved in four of five (80%) of the patients who went on to surgery, while one patient had negative margins on frozen section but microscopically positive margins on permanent section. Three of five patients (60%) recurred after surgery; two of these patients died with recurrent/metastatic ENB. In summary, induction therapy may facilitate margin-negative resection in locally advanced ENB. Given the apparent sensitivity of ENB to chemotherapy and radiotherapy, future prospective studies should investigate the optimal multidisciplinary approach to improve long-term survival in this rare disease.

ObjectivesTo assess the outcomes of abdominal dermal‐fat grafting following superficial and total parotidectomy.MethodsA retrospective chart review of parotidectomy patients was performed. Patients were divided into four groups based on surgical extent and grafting status: superficial parotidectomy (SP), superficial parotidectomy with grafting (SPg), total parotidectomy (TP), and total parotidectomy with grafting (TPg). Complication rates and operative times were then compared between surgically matched groups (SP vs. SPg, TP vs. TPg). Complications included graft necrosis, gustatory sweating, first‐bite syndrome, infection, hematoma, sialocele, and seroma. Data was analyzed via chi‐square and two‐sample t testing, logistic regression, and one‐way analysis of variance.ResultsThe cohort consisted of 330 patients: 106 SP (32.12%), 61 SPg (18.48%), 82 TP (24.85%), and 81 TPg (24.55%). No donor site complications occurred. TPg resulted in seven graft necroses (8.64%), and 22 reported gustatory sweating (27.20% vs. 10 TP patients (12.2%), P = 0.016); SPg resulted in two necroses (3.28%). There were no other statistically significant differences in complication rates. Graft recipients receiving adjuvant radiation were more likely to develop necrosis (odds ratio [OR] 4.60, 95% confidence interval [CI], 1.16–18.27, P = .0194). Patients who developed gustatory sweating were 8.38 years younger (95% CI 2.66–14.10, P = 0.002, follow‐up time > 48 days). Grafting did not increase operative times (TP/TPg: mean = 275.91/263.65 minutes, standard error of the mean = 41.96/33.75, P = 0.822).ConclusionAn abdominal dermal‐fat graft is an excellent reconstructive choice for a parotidectomy defect and is not associated with increased complication rates or prolonged operative time.Level of Evidence4 Laryngoscope, 130:2144–2147, 2020