Artificial intelligence-based epigenomic, transcriptomic and histologic signatures of tobacco use in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) biomarker studies rarely employ multi-omic biomarker strategies and pertinent clinicopathologic characteristics to predict mortality. In this study we determine for the first time a combined epigenetic, gene expression, and histology signature that differentiates between patients with different tobacco use history (heavy tobacco use with ≥10 pack years vs. no tobacco use). Using The Cancer Genome Atlas (TCGA) cohort (n = 257) and an internal cohort (n = 40), we identify 3 epigenetic markers (GPR15, GNG12, GDNF) and 13 expression markers (IGHA2, SCG5, RPL3L, NTRK1, CD96, BMP6, TFPI2, EFEMP2, RYR3, DMTN, GPD2, BAALC, and FMO3), which are dysregulated in OSCC patients who were never smokers vs. those who have a ≥ 10 pack year history. While mortality risk prediction based on smoking status and clinicopathologic covariates alone is inaccurate (c-statistic = 0.57), the combined epigenetic/expression and histologic signature has a c-statistic = 0.9409 in predicting 5-year mortality in OSCC patients.

Maackia amurensis seed lectin (MASL) and soluble human podoplanin (shPDPN) sequence analysis and effects on human oral squamous cell carcinoma (OSCC) cell migration and viability.

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent.

Patterns and Trends in Adjuvant Therapy for Major Salivary Gland Cancer.

OBJECTIVE: To investigate adjuvant therapy indications, utilization, and associated survival disparities in major salivary gland cancer (MSGC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2006 to 2017 National Cancer Database. METHODS: Patients with surgically resected MSGC were included (N = 11,398). pT3-4 classification, pN2-3 classification, lymphovascular invasion, pathologic extranodal extension (pENE), and positive surgical margin (PSM) were considered indications for adjuvant radiotherapy (aRT). pENE and PSM were considered possible indications for adjuvant chemotherapy. Multivariable logistic and Cox regression models were implemented. RESULTS: Among 6694 patients with ≥ $\ge $ 1 indication for aRT, 1906 (28.5%) received no further treatment and missed aRT. Age, race, comorbidity status, facility type, and distance to reporting facility were associated with missed aRT (P < .025). Among 4003 patients with ≥1 possible indication for adjuvant chemoradiotherapy (aCRT), 914 (22.8%) received aCRT. Patients with pENE only (38.5%) and both pENE and PSM (44.0%) received aCRT more frequently than those with PSM only (17.0%) (P < .001). Academic facility was associated with aCRT utilization (P < .05). aCRT utilization increased between 2006 and 2017 in both academic (14.8% vs 23.9%) and nonacademic (8.8% vs 13.5%) facilities (P < .05). Among 2691 patients with ≥1 indication for aRT alone, missed aRT portended poorer OS (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.28-2.03, P < .001). Among 4003 patients with ≥1 possible indication for aCRT, aRT alone (HR: 1.02, 95% CI: 0.89-1.18, P = .780) and aCRT were associated with similar OS. CONCLUSION: Missed aRT in MSGC occurs frequently and portends poorer OS. Further studies clarifying indications for aCRT are required.

Adjuvant Radiation and Survival Following Surgical Resection of Sinonasal Adenocarcinoma.

OBJECTIVES: This study aims to investigate the utility of adjuvant radiation in patients who undergo surgical resection for the management of node-negative sinonasal adenocarcinoma (SNAC). STUDY DESIGN: Retrospective database review. METHODS: The 2004-2016 National Cancer Data Base (NCDB) was used to extract patients with surgically resected node-negative SNAC. Kaplan-Meier survival analysis and Cox-Proportional Hazards Modelling were used to analyze the impact of adjuvant radiation on overall survival (OS) following surgery. RESULTS: 349 patients with SNAC underwent surgical resection. Of these patients, 154 (44.1%) received adjuvant radiotherapy (RT). Although there was no significant difference in race, age, or sex of those receiving RT, those receiving RT have more advanced diseases and are more likely to have positive margins. Kaplan Meier analysis showed no significant difference in 5-year OS in patient who received adjuvant RT in comparison to those who underwent surgical resection alone (65.7% vs. 72.6%, respectively; p = 0.378). In addition, when looking at only patients with positive margins, 5-year OS still did not have a significant difference (73.8% vs. 61.6%, respectively; p = 0.101). Only patients with clinical AJCC T4 showed a statistically significant survival benefit with adjuvant RT (56.9% vs. 29.9%, respectively; p = 0.009). CONCLUSIONS: Adjuvant RT does not appear to provide a significant survival benefit in patients with resected SNAC, with the exception of those with clinically AJCC T4 disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2603-2612, 2023.

Mucosal Melanoma of the Oral Cavity: What is the Role of Elective Neck Dissection?

OBJECTIVES: Mucosal melanoma (MM) is a rare malignancy that can present in the head and neck (H&N). The Oral cavity is the second most common primary site in the H&N after sinonasal mucosa. This study investigates the impact of demographic and clinical factors on survival in oral cavity MM. Further, it investigates the outcomes and utility of elective neck dissections (END) in the management of oral MM. METHODS: The National Cancer Database was used to evaluate 432 patients with oral cavity MM from 2004 to 2016. Kaplan-Meir and Cox regression analyses were used to determine variables associated with survival. RESULTS: The mean age was 64.0 ± 16.0 years. Most patients were white (85.1%) and male (60.0%). Gingiva (37.6%) and hard palate (36.1%) were the most common primary subsites in the oral cavity. Five-year overall survival was 31.0%. Age (Hazards Ratio [95% Confidence Interval], 1.03 [1.01-1.06]), N-stage (1.94 [1.10-3.42]), M-stage (10.13 [3.33-30.86]), male sex (1.79 [1.06-3.03]), and African-American race (2.63 [1.14-6.11]) were significantly associated with worse survival. 199 patients (46.9%) underwent neck dissection including 118 with lymph node yield (LNY) ≥ 18. The rate of occult nodal positivity was 45.4% for LNY ≥ 18 and 28.3% for LNY ≥ 1. ENDs were not associated with improved outcomes. However, occult lymph node involvement was associated with worse overall survival (p = 0.004). CONCLUSIONS: Oral cavity MM has a poor prognosis. Lymph node involvement, distant metastasis, age, race, and male sex are associated with worse outcomes. Performing an END did not improve survival. However, END may have a prognostic role and help select patients for treatment intensification. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:317-326, 2023.

Prognostic significance of head and neck spindle cell carcinoma.

BACKGROUND: Our study investigates the prognostic significance of spindle cell histology on overall survival (OS) of conventional head and neck squamous cell carcinoma (HNSCC). METHODS: The 2004 to 2017 National Cancer Database was queried for patients with head and neck spindle cell carcinoma (HNSpCC) (n = 1572) or HNSCC (n = 242 697) of the oral cavity, major salivary glands, sinonasal tract, oropharynx, hypopharynx, and larynx treated with curative intent. RESULTS: Patients with HNSpCC presented more frequently with higher-grade tumors and cN0 disease than those with HNSCC (p < 0.001). In the oral cavity, the HR for death for SpCC compared with SCC was 1.33 (p < 0.001). In the oropharynx, the HR for death for SpCC compared with SCC was 1.47 (p = 0.028). CONCLUSIONS: After adjusting for patient, tumor, and treatment characteristics, SpCC histology had an independent adverse prognostic effect on OS in the oral cavity and oropharynx. SpCC histology does not necessarily portend poorer survival in all HNSCC.

Brush swab as a noninvasive surrogate for tissue biopsies in epigenomic profiling of oral cancer.

BACKGROUND: Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients. METHODS: Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies. RESULTS: There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11). CONCLUSIONS: Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.

Evaluating the impact of metabolic syndrome on postoperative thyroidectomy outcomes.

OBJECTIVE: Metabolic syndrome (MetS) has previously been linked to increased risk of postoperative morbidity and mortality in other surgical undertakings. Because MetS is a consequence of endocrine dysfunction, and given the thyroid's crucial role in endocrine homeostasis, we sought to evaluate the association between MetS and postoperative outcomes of thyroidectomy. METHODS: Data were acquired from the ACS-NSQIP database from years 2005 to 2017. Patients with obesity, diabetes, and hypertension were defined as having MetS. Odds ratios (OR) were obtained for outcomes to quantify risk with multivariate logistic regression. RESULTS: Outcomes significantly affected by MetS included overall complication (OR: 2.00), extended postoperative stay (OR: 1.52), medical complication (OR: 1.48), surgical complication (OR: 1.62), and mortality (OR: 2.33). CONCLUSIONS: Patients with MetS undergoing thyroidectomy are at increased risk of an increased length of stay, overall complications, and mortality.

The Benefit of Primary Tumor Surgical Resection in Distant Metastatic Carcinomas of the Thyroid.

OBJECTIVES/HYPOTHESIS: Thyroid cancer with distant metastasis (TCDM) at diagnosis has significantly worse survival rates when compared to localized/regional thyroid cancer. This study sought to report on the characteristics of patients presenting with TCDM and the potential survival advantage of surgical resection. STUDY DESIGN: Data were acquired from the Surveillance, Epidemiology, and End Results (SEER) database with cases from 2004 to 2015. METHODS: TCDM cases (n = 2,558) were identified from the SEER database. The Bonferroni correction was applied for multivariate analysis. Kaplan-Meier analysis was utilized to obtain disease-specific survival (DSS) rates. Cox regression analysis was utilized to identify independent factors significantly associated with survival. RESULTS: The average age of diagnosis of TCDM was 62.0 (±17.5) years. Patients were predominantly white (74.6%), female (54.6%), in a relationship (56.0%), and between ages 36 and 80 years (76.4%). Cases consisted of papillary (57.2%), follicular (16.0%), medullary (8.9%), anaplastic (17.9%) TCDM histological variants. Overall 1-, 5-, and 10-year DSS rates were 72.0%, 56.8%, and 43.8%, respectively. Anaplastic and medullary variants had the worst 10-year DSS (0% and 25.5%, respectively). Patients who underwent surgical resection only and surgical resection with radiation were 49% and 59% less likely to die, respectively. Treatment, age, histology, T staging, relationship status, and metastasis site were determined to be significant predictors of survival. CONCLUSIONS: Surgical resection with radiation was found to be a significant predictor of survival after applying the Bonferroni correction for all thyroid cancer variants except medullary. To increase survival, surgical intervention should be recommended in patients who are deemed to be medically tolerant of surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1026-1034, 2021.

Evaluating the impact of smoking on disease-specific survival outcomes in patients with human papillomavirus-associated oropharyngeal cancer treated with transoral robotic surgery.

BACKGROUND: When treated nonsurgically with definitive chemoradiation, smokers with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a worse prognosis compared with their nonsmoking counterparts. To the authors' knowledge, the prognostic significance of smoking in surgically treated patients is unknown. METHODS: The current study is a retrospective case series of patients with HPV-positive OPSCC who underwent upfront transoral robotic surgery at a single institution from 2010 through 2017. Exclusion criteria were nonoropharyngeal primary tumors, histology other than SCC, HPV-negative tumors, previous history of head and neck cancer, and/or previous head and neck radiotherapy. Recurrence-free survival (RFS), overall survival, and disease-specific survival were compared using the Kaplan-Meier method and the log-rank test. Smoking history was categorized as never smokers (<1 pack-year), current smokers (smoking at the time of the cancer diagnosis), and former smokers. RESULTS: A total of 258 patients met the study criteria. The average age was 60 years, and approximately 87% of patients were male. A total of 148 patients (57.4%) were smokers whereas 110 (42.6%) reported never smoking. There were 44 active smokers (17.1%) and 104 former smokers (40.3%). The median follow-up was 3.23 years. There were 17 patients of disease recurrence. Smoking pack-year history was not found to be significant for RFS (hazard ratio, 1.01; 95% CI, 0.99-1.03 [P = .45]). There was no significant difference in RFS noted between never and ever smokers (92% vs 89.8%; P = .85) nor was there a difference observed between never, former, and current smokers (92% vs 91.5% vs 86.1%, respectively; P = .69). CONCLUSIONS: A smoking history is common in patients with HPV-positive OPSCC. In the current study, HPV-positive smokers were found to have excellent survival and locoregional control, similar to their nonsmoking counterparts. The results of the current study do not support the exclusion of smokers with early-stage, HPV-positive OPSCC from transoral robotic surgery-based deintensification trials.

Virtual Surgical Planning in Subscapular System Free Flap Reconstruction of Midface Defects.

OBJECTIVES: Reconstruction of the midface has many inherent challenges, including orbital support, skull base reconstruction, optimizing midface projection, separation of the nasal cavity and dental rehabilitation. Subscapular system free flaps (SF) have sufficient bone stock to support complex reconstruction and the option of separate soft tissue components. This study analyzes the effect of virtual surgical planning (VSP) in SF for midface on subsite reconstruction, bone segment contact and anatomic position. MATERIALS AND METHODS: Retrospective cohort of patients with midface defects that underwent SF reconstruction at a single tertiary care institution. RESULTS: Nine cases with VSP were compared to fourteen cases without VSP. VSP was associated with a higher number of successfully reconstructed subunits (5.9 vs 4.2, 95% CI of mean difference 0.31-3.04, p = 0.018), a higher number of successful bony contact between segments (2.2 vs 1.4, 95% CI of mean difference 0.0-1.6, p = 0.050), and a higher percent of segments in anatomic position (100% vs 71%, 95% CI of mean difference 2-55%, p = 0.035). When postoperative bone position after VSP reconstruction was compared to preoperative scans, the difference in anteroposterior, vertical and lateral projection compared to the preoperative 'ideal' bone position was <1 cm in 82% of measurements. There were no flap losses. CONCLUSION: VSP may augment SF reconstruction of the midface by allowing for improved subunit reconstruction, bony segment contact and anatomically correct bone segment positioning. VSP can be a useful adjunct for complex midface reconstruction and the benefits should be weighed against cost.

Evaluation of oncologic outcomes in head and neck cancer patients ≥80 years old based on adherence to NCCN guideline for postoperative adjuvant treatment.

BACKGROUND: There is a paucity of literature characterizing outcomes in older adult patients with head and neck cancer (HNC). This study aims to describe patients from this group, their adherence to National Comprehensive Cancer Network (NCCN) adjuvant treatment guidelines, and the impact of guideline adherence on overall survival (OS). METHODS: In this retrospective cohort study, we reviewed all patients ≥80 years old with HNC who underwent surgery with curative intent from 2008 to 2016. Adherence to NCCN guidelines was determined in blinded fashion, and quality metrics and OS were compared. RESULTS: One hundred fifty-nine patients met inclusion criteria. The majority of patients (n = 94, 59%) underwent treatment in accordance with NCCN recommendations while 65 (41%) deviated from NCCN guidelines. The two cohorts did not demonstrate a difference in 2-year OS (62% vs 66%, P = .50). CONCLUSION: Older adult patient outcomes were not different when treatment deviated from NCCN guidelines.

Autologous Fat Grafting Restores Soft-tissue Contour Deformities after Vascular Anomaly Surgery.

BACKGROUND: Soft-tissue loss is expected after resection of large vascular lesions. Autologous fat transfer improves asymmetries; however, systematic outcomes are not previously described for vascular anomaly reconstruction. METHODS: Retrospective chart review from 2012 to 2015 included patients receiving autologous fat transfers for soft-tissue defects during or following vascular anomaly surgery at a tertiary care center. Patients received dermal en bloc fat grafts, lipoaspirates, or both. Pre- and postoperative photographs were blindly reviewed by 3 facial plastic surgeons using a 5-point scale. Dermal abdominal en bloc fat grafts were placed immediately after excision of a vascular anomaly. Lipoaspirate fat grafting was performed using liposuction (modified Coleman technique) and centrifugation. The effectiveness of fat transfers was assessed using patients' photographs. Final follow-up was 6 months to 5 years. RESULTS: There were 35 autologous fat transfer surgeries in 27 patients. Fourteen patients received en bloc dermal fat grafts (14 total), 13 lipoaspirate transfers (21 total), and 3 both. Ages ranged from 2 to 69 years (mean = 25 years). Majority of patients (81%) had head and neck lesions. Average volume of fat injected was 16.5 mL (range 0.8-100 mL). The average observer rating score was 2.45 [1-5 (5-point scale)] in the en bloc fat graft group versus 3.83 in the lipoaspirate group (P < 0.0001) with acceptable inter-rater reliability between 3 observers (coefficient of concordance = 0.76). Follow-up ranged from 6 months to 5 years. There were 2 complications in the dermal fat graft group and none in the lipoaspirate group. CONCLUSIONS: Autologous fat transfer improves symmetry and scarring after surgical treatment of vascular anomalies. Fat grafting is permanent and reliable and creates a more symmetric soft-tissue contour compared with dermal fat grafts.

Survival of oral tongue squamous cell carcinoma in young adults.

BACKGROUND: Small cohort studies have suggested oral tongue squamous cell carcinoma (OTSCC) could be associated with worse prognosis in individuals younger than 40. METHODS: We compared the survival of all OTSCC cases in the National Cancer Database under 40 years old with those older than 40, excluding patients over 70. Cox regression and propensity score matched (PSM) survival analyses were performed. RESULTS: A total of 22 930 OTSCC patients were identified. The under 40 group consisted of 2566 (9.9%) cases; 20664 were 40 to 70 (90.1%). Most were male (13 713, 59.8%), stage I-II (12 754, 72.4%), and treated by surgery alone (13 973, 63.2%). Survival in patients under 40 was higher (79.6% vs 69.5%, P < .001). In PSM analysis (n = 2928) controlling for all 10 significant factors in multivariate regression, patients under 40 had a 9% higher 5-year survival (77.1% vs 68.2%, P < .001). CONCLUSION: Contrary to the prior reports, younger patients with OTSCC did not have worse survival in the National Cancer Database.

Patterns of Care and Outcome of Clear Cell Carcinoma of the Head and Neck.

OBJECTIVE: Clear cell carcinoma (CCC) is a rare salivary gland malignancy, believed to be generally low grade. We investigated CCC epidemiology and clinical behavior, using the National Cancer Database (NCDB). STUDY DESIGN: Retrospective cohort study. SETTING: NCDB. SUBJECTS AND METHODS: All CCCs of the salivary glands were selected between 2004 and 2015. Patient demographics, tumor characteristics, treatments, and survival were analyzed. Cox regression analyses were performed in treated patients. RESULTS: We identified 268 patients with CCC. Median age was 61 (21-90) years. Most were female (145, 54%). The most common site was oral cavity (119, 44%), followed by major salivary glands (68, 25%) and oropharynx (41, 15%). Most tumors were low grade (81, 68%) and stages I to II (117, 60.6%). Nodal (36, 17.5%) and distant metastases (6, 2.4%) were rare. Most were treated by surgery alone (134, 50.0%), followed by surgery and radiotherapy (69, 25.7%). Five-year overall survival (OS) was 77.6% (95% CI, 71.4%-84.2%). In univariate analysis, older age, major salivary gland and sinonasal site, stages III to IV, high grade, and positive margins were associated with worse OS. In multivariate analysis, only high tumor grade (hazard ratio [HR], 5.76; 95% CI, 1.39-23.85; P = .02), positive margins (HR, 4.01; 95% CI, 1.20-13.43; P = .02), and age ≥60 years (HR, 3.45; 95% CI, 1.39-8.55; P = .01) were significantly associated with OS. CONCLUSION: We report the largest series of clear cell carcinomas of the head and neck. Outcomes are generally favorable following surgical-based treatments. In this series, pathologic tumor grade is associated with worse survival. Routine evaluation and reporting of tumor grade might better guide physicians in recommending appropriate treatments in this rare malignancy.

Perioperative Management of Total Laryngectomy Patients: A Survey of American Head and Neck Society Surgeons.

OBJECTIVES: Standards of care for total laryngectomy (TL) patients in the postoperative period have not been established. Perioperative care remains highly variable and perhaps primarily anecdotally based. The aim of this study was to survey members of the American Head and Neck Society to capture management practices in the perioperative care of TL patients. METHODS: In this survey study, an electronic survey was distributed to the international attending physician body of the American Head and Neck Society. Forty-five-question electronic surveys were distributed. A total of 777 members were invited to respond, of whom 177 (22.8%) fully completed the survey. The survey elicited information on management preferences in the perioperative care of TL patients. Differences in management on the basis of irradiation status and pharyngeal repair (primary closure vs regional or free flap reconstruction) were ascertained. Main outcomes and measures were time to initiate oral feeding, perioperative antibiotic selection and duration, and estimated pharyngocutaneous fistula rates. These measures were stratified by patient type. RESULTS: Most respondents completed head and neck fellowships (77.0%) and practice at academic tertiary centers (72.3%). Ampicillin/sulbactam was the most preferred perioperative antibiotic (43.2%-49.1% depending on patient type), followed by cefazolin and metronidazole in combination (32.0%-33.7%) and then clindamycin (10.8%-12.6%). Compared with nonirradiated patients, irradiated patients were significantly more likely to have longer durations of antibiotics ( P < .05), longer postoperative times to initiate oral feeding ( P < .05), and higher estimated fistula rates ( P < .05). Additionally, in nonirradiated patients, flap-repaired patients (vs primary repair) were significantly more likely to have longer durations of antibiotics (odds ratio, 1.29; 95% confidence interval, 1.13-1.48) and postoperative times to initiate oral feeding (odds ratio, 2.24; 95% confidence interval, 1.76-2.84). CONCLUSIONS: Perioperative management of TL patients is highly variable. Management of antibiotics and oral feeding are significantly affected by irradiation status and scope of pharyngeal repair. Further studies are needed to standardize perioperative care for this unique patient population.

Tracheal replacement revisited: Use of a vascularized tracheal transplant in a porcine model.

OBJECTIVES/HYPOTHESIS: To determine if a long segment of trachea can be transplanted as a vascularized organ and to determine if a tracheal transplant is a potential surgical option for a long-segment circumferential tracheal defect. STUDY DESIGN: Animal model. METHODS: Four (two donors and two recipients) adult domestic Yorkshire swine were used. Two sets of transplants were performed from a donor to recipient pig. The transplant was placed heterotopically (not in continuity with the airway), and the recipient animals were monitored for 14 days to ensure the transplants were well vascularized. Immunosuppressive therapies included methylprednisolone, cyclosporine, and azathioprine. Gross as well as histological examination of multiple tissues types including mucosa, cartilage, muscle, and blood vessels were performed postsacrifice on day 14. RESULTS: Recipient animal weights ranged from 40 to 42 kilograms. Both recipient pigs survived the full 14 days of study and exhibited normal activity and appetite. Ischemia time of transplanted grafts ranged from 63 to 72 minutes. Transplanted tracheas included a minimum of 15 cartilaginous rings and measured greater than 10 cm in length. Both grafts maintained a robust blood supply throughout the duration of study. CONCLUSIONS: The entire visceral compartment can be reliably transplanted, either as a single component (trachea) or as a chimeric flap with multiple components (trachea, esophagus, larynx, and pharynx). Further studies in the swine model should be considered to study the effects of transplanting the trachea orthotopically into the native airway. Further studies are needed into the reliability of this technique of transplantation in humans. LEVEL OF EVIDENCE: NA Laryngoscope, 128:S1-S9, 2018.

Patterns of care and outcomes of adjuvant therapy for high-risk head and neck cancer after surgery.

BACKGROUND: Postoperative chemoradiotherapy (CRT) is considered standard of care in patients with locally advanced head and neck cancer with positive margins and/or extracapsular extension (ECE). METHODS: The National Cancer Data Base (NCDB) was queried to identify patients with squamous cell carcinoma of the head and neck with stages III to IVB disease or with positive margins and/or ECE diagnosed between 2004 and 2012 receiving postoperative radiotherapy (RT). Using univariable and multivariable logistic and Cox regression, we assessed for predictors of CRT use and covariables impacting overall survival (OS), including in a propensity-matched subset. RESULTS: Of 12 224 patients, 67.1% with positive margins and/or ECE received CRT as well as 54.0% without positive margins and/or ECE. The 5-year OS was 61.6% for RT alone versus 67.4% for CRT. In the propensity-matched cohort, OS benefit persisted with CRT, including in a subset with positive margins and/or ECE but not without. CONCLUSION: Postoperative CRT seems underutilized with positive margins and/or ECE and overutilized without positive margins and/or ECE. The CRT was associated with improved OS but the benefit persisted only in the subset with positive margins and/or ECE.