Clinical applications of vascularized fascia lata in head and neck reconstruction: A systematic review.

BACKGROUND: Given limitations in the current literature, the precise indications, techniques, and outcomes relevant to vascularized fascia lata free flap reconstruction remain uncertain. The objective of this study was to perform a systematic review of published literature to evaluate indications, methods, and complications for vascularized fascia lata free flap reconstruction. METHODS: A systematic review of the literature was performed using a set of search criteria to identify patients who underwent free flap reconstruction of the head and neck region using vascularized fascia lata. Articles were reviewed based on relevance, with the primary outcome being surgical complications and surgical indications. RESULTS: A comprehensive search revealed 783 articles and 5 articles were ultimately found to be appropriate to this review- 55 patients undergoing free flap reconstruction were identified. Overall complication rates were 10.9 % for major complications and 18.1 % for minor complications. Follow-up spanned 1 to 95 months with a median of 48 months. CONCLUSIONS: Microvascular reconstruction of the head and neck with vascularized fascia lata is achievable with high adaptability and reliability reported in the literature.

Chimeric Versus Multiple Simultaneous Free Flaps for Head and Neck Reconstruction.

OBJECTIVE: To describe our experience with chimeric flaps and to assess the surgical outcomes and postoperative complications associated with chimeric flaps compared to multiple flaps. STUDY DESIGN/METHODS: Patients undergoing chimeric and multiple simultaneous free tissue transfer between June 2016 and October 2023 were retrospectively reviewed. The primary outcome of interest was the complication rate. Major complications required takeback to the operating room, hospital readmission, or transfer to the intensive care unit. Minor complications were managed conservatively. Secondary outcomes included operative time, length of hospitalization, and flap survival. SETTING: Academic tertiary care center. RESULTS: Our analysis included 113 patients (chimeric n = 38, multiple n = 75). We found no significant difference in operative times or minor complications. Chimeric flaps were associated with a shorter length of hospitalization. The major complication rate was higher for chimeric flaps (42.1% vs 22.7%, P = .03), but each cohort only had 1 instance of total flap loss. CONCLUSION: The complexity of large head and neck defects poses a reconstructive challenge for microvascular surgeons. Our findings suggest that chimeric and multiple flaps both produce acceptable complication rates when used appropriately. Differences in complication rates may reflect differences in utilization. The chimeric flap remains a valuable option for those with prior radiation or radical resection, but it remains unclear the degree to which they lessen the inherent risk of postoperative complications within this population. Each technique must be weighed in context of the patient's reconstructive profile and the institution's surgical capabilities to optimize long-term outcomes.

Prognostic significance of hemorrhage requiring embolization in the setting of previously treated head and neck squamous cell carcinoma: Systematic review and retrospective cohort.

BACKGROUND: The management of acute hemorrhage in patients with previously treated head and neck squamous cell carcinoma (HNSCC) is challenging due to the lack of substantial evidence to guide clinical decision making. METHODS: A systematic review and retrospective chart review were performed to identify patients with a history of HNSCC who underwent either primary or adjuvant radiation therapy (RT) and presented with hemorrhagic complications requiring embolization. Patient characteristics, history, presentation, and outcomes were reviewed. RESULTS: The systematic review included a total of 182 patients. Heterogeneity existed in outcomes reporting; 1-year overall survival approached 50%. From the retrospective chart review, 51 patients were included. Median survival time following hemorrhage was 2.2 months (range 1.2-11.4 months). Patients with malignancy at time of hemorrhage were identified as having worse survival. CONCLUSIONS: Acute hemorrhage in patients with a history of previously radiated HNSCC portends a high risk of mortality, with patients with active malignancy representing a worse prognostic group.

Fibula Free Flap Reconstruction of Cervical Spine Defects: A Multi-Institutional Study.

INTRODUCTION: Cervical spine defects result in spinal instability, putting the spinal cord and vertebral arteries at risk of damage and possibly devastating neurological injuries. The fibula free flap can span the spinal defects for stability. There is a paucity of literature on this technique. METHOD: Multi-institutional retrospective case series reviewing patients who underwent cervical spine reconstruction with a fibula free flap. Patient demographic information, comorbidities, characteristics of cervical spine defects, and free flap complications were collected. RESULTS: A total of 1187 fibula free flaps across 10 different institutions were reviewed. Thirteen patients (1.09%) underwent cervical spine reconstruction with a fibula free flap. Average age was 52.3 years old with an age range of 12-79 years. There were six males (46.1%) and seven females (53.8%). The most common defect etiology was infection (n = 6, 46.1%). Most commonly involved cervical spine level of the defect was C5 (n = 10) followed by C6 (n = 9) and C4 (n = 8). The majority of reconstructed defects spanned three or more cervical levels, (n = 9, 69.2%). Facial artery was the most common arterial anastomosis (n = 8). Eight patients (61.5%) required a tracheostomy during their postoperative course. None of the patients had symptomatic or radiographic nonunion. CONCLUSION: This case series demonstrates that a vascularized fibula flap is a potential reconstructive option for cervical spine defects, especially in defects greater than three cervical levels, in the setting of infection, and previously radiated patients. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Microvascular reconstruction of midface osteoradionecrosis.

BACKGROUND: Head and neck osteoradionecrosis (ORN) of the midface requiring free flap (FF) reconstruction is uncommon. This multi-institutional study was designed to review outcomes for this rare patient population. METHODS: Retrospective multi-institutional review of FF reconstruction for midface ORN (2005-2022; n = 54). RESULTS: The FF survival rate was 87% (n = 54). Patients were less likely to be tolerating a regular diet at 3 months postoperative if they had a preoperative history of prior head and surgery (80% vs. 95%; p = 0.02), a pathologic fracture (50% vs. 90%; p = 0.04), exposed bone intraorally (43% vs. 94%; p = 0.002), or a fistula (67% vs. 96%; p = 0.03). Mean albumin was higher in patients whose FF survived (3.6 ± 0.5 vs. 2.7 ± 1.4; p = 0.03). Patients with low prealbumin were more likely to undergo a hematoma evacuation (27% vs. 0%; p = 0.02). CONCLUSION: In this series of midface ORN requiring FF reconstruction preoperative nutritional status impacted postoperative complications. Preoperative occurrence of a fistula, pathologic fracture, and intraoral bone exposure correlated with decreased tolerance of a regular diet following reconstruction.

A hybrid epithelial/mesenchymal state in head and neck cancer: A biomarker for survival with differential prognosis by self-reported race.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the 6th leading cause of cancer-related mortality, with racial disparities amplifying the challenges in treatment. Although the relationship between hybrid epithelial/mesenchymal (E/M) states and tumor progression is of interest, no studies have characterized the clinical relevance of hybrid E/M states in head and neck cancer outcomes among self-reported racial cohorts. METHODS: Given the overlap in gene expression between hybrid E/M malignant cells and cancer-associated fibroblasts, we utilized deconvolution of bulk RNA sequencing data from oral cavity and laryngeal squamous cell carcinoma tumors from The Cancer Genome Atlas. We utilized our previously collected single-cell profiles to generate inferred malignant profiles and then scored these for hybrid E/M. We then conducted a survival analysis on overall and disease-free survival among self-reported Black and White Americans. FINDINGS: The hybrid E/M state was differentially associated with head and neck cancer survival by self-reported race and ethnicity, with a stronger association in non-Hispanic Black patients. Black patients with a high hybrid E/M score had a higher risk of death or recurrence (hazard ratio [HR]: 4.18 [95% confidence interval (CI): 2.06, 8.49]) than White patients with a high hybrid E/M score (HR: 1.58 [95% CI: 1.11, 2.26]). CONCLUSION: Our results suggest a complex interplay of social structure, racism, and genetic diversity. We implore researchers to consider the social and biological context contributing to disparities. FUNDING: A.L.M. received support from the National Institute of Minority Health and Health Disparities (K01MD013897 [principal investigator (PI), A.L.M.]). S.V.P. received support from the National Institute of Dental and Craniofacial Research (R01DE032865 [PI, S.V.P.] and R01DE032371 [PI, S.V.P.]).

Trends in ototoxicity monitoring among cisplatin-treated patients with cancer.

PURPOSE: This study aims to characterize patterns in ototoxicity monitoring and identify potential barriers to audiologic follow-up. METHODS: We performed a single-institution retrospective cohort study on adult (≥ 18 years old) cancer patients treated with cisplatin from January 2014 to September 2021. Our primary outcomes were rates of baseline and post-treatment audiograms at the following time points: 3, 6, 12, and greater than 12 months. Time-to-event analyses were performed to describe additional insights to ototoxicity monitoring patterns. RESULTS: Nine hundred fifty-five patients with cancer were included for analysis. The most common primary cancer sites were head and neck (64%), followed by cervical (24%). Three hundred seventy-three patients (39%) underwent baseline audiometric assessment, 38 patients (4%) received audiologic evaluation during chemotherapy, and 346 patients (36%) obtained at least one post-treatment audiogram. Audiologic follow-up was greatest within 3 months of completing chemotherapy (26%), but this tapered dramatically to less than 10% at every other post-treatment time point. Patients with head and neck cancer achieved higher rates of audiologic follow-up at every time point than patients with non-head and neck cancer except for during treatment. CONCLUSIONS: Ototoxicity monitoring is an inconsistent practice, particularly during chemotherapy and for long-term surveillance of hearing loss. Patients with non-head and neck cancer may be at increased risk for loss of audiologic follow-up. IMPLICATIONS FOR CANCER SURVIVORS: Cisplatin ototoxicity is a common occurrence that can be effectively managed with auditory rehabilitation. Therefore, referrals to audiology and counseling on treatment-related ototoxicity are recommended throughout chemotherapy and cancer survivorship.

Airway protection and outcomes after staged versus concurrent bilateral neck dissections with transoral base of tongue cancer resection.

OBJECTIVES: To assess airway, safety, and resource utilization outcomes between transoral base of tongue (BOT) surgery with staged versus concurrent bilateral neck dissections (BND). METHODS: A retrospective cohort study of patients with human papilloma virus (HPV)-related BOT cancer who underwent transoral surgery and BND from January 2015 through June 2022 was conducted. Free flap patients were excluded. RESULTS: Of 126 patients (46 [37%] staged and 80 [63%] concurrent BND), there were no significant differences in rates of postoperative intubation, tracheostomy, intensive care admission, operative takebacks, gastrostomy, and 30-day readmission. Total operative time (median difference 1.4 [95% CI 0.9-1.8] hours), length of stay (1.0 [1.0-1.0] day), and time between primary surgery and adjuvant therapy initiation (4.0 [0.0-8.0] days) were lower in the concurrent BND cohort. CONCLUSION: Concurrent BND alongside transoral BOT resection is safe with similar airway outcomes and lower total operative time, length of stay, and time to adjuvant therapy initiation compared to staged BND.

Microvascular reconstruction of medication related osteonecrosis of the head and neck.

BACKGROUND: Medication related osteonecrosis of the jaw (MRONJ) requiring free flap (FF) reconstruction is uncommon with limited reported findings. METHODS: Multicenter, retrospective case series of 49 consecutive adult patients presenting with advanced MRONJ requiring FF reconstruction from 2010 to 2022. Perioperative complications and outcomes were analyzed. RESULTS: Eighty-two percent (n = 40) of cases were of the mandible and 18% (n = 9) were of the maxilla. The mean follow-up was 15 months (±19.6). The majority of FF survived (96%, n = 47). FF reconstructions of the maxilla were more likely to require postoperative debridement (56%, 95% CI [27, 81%] vs. 15%, 95% CI [7, 25%], p = 0.008) or develop intraoral bone exposure (56%, 95% CI [27, 81%] vs. 18%, 95% CI [9, 27%], p = 0.02). Most patients (71%, n = 35) received preoperative antibiotics which was associated with a higher rate of FF survival (100% vs. 86%, 95% CI [60, 96%], p = 0.02) and fewer complications. CONCLUSIONS: Patients undergoing FF reconstruction for MRONJ do well with high rates of FF success. MRONJ of the maxilla have a higher rate of some complications. Preoperative antibiotics correlated with higher FF survival and fewer postoperative complications.

Poor Dental Health as a Risk Factor for Alveolar Ridge Malignancies.

OBJECTIVE: To determine the association between poor dental health and risk of oral cavity squamous cell cancer (OCSCC) at individual tumor subsites. STUDY DESIGN: Case-control and cross-sectional METHODS: A case-control study was performed using a population-based cohort in North Carolina (Carolina Head and Neck Cancer Epidemiology Study [CHANCE]). A secondary cross-sectional analysis was performed with an institutional cohort (WashU/Siteman). Cases were adults with primary OCSCC and an identifiable tumor subsite. In the CHANCE cohort, controls were adults without head and neck cancer. In the Washington University/Siteman cohort, patients with tongue cancer served as the comparator group. We used number of missing teeth (categorized 0-6, 7-24, 25-28) as a surrogate for poor dental health, which was self-reported in CHANCE and measured on a pretreatment computed tomography scan in the WashU/Siteman study. Adjusted odds ratios (aORs) for missing teeth were estimated for each tumor subsite using binomial logistic regression models. RESULTS: Near complete tooth loss (25-28 teeth) was associated with a 3.5-fold increased risk of alveolar ridge malignancy (aOR: 3.51; 95% confidence interval [CI]: 1.14-11.01, P = .03) in the CHANCE study. This association was confirmed in our cross-sectional analysis (WashU/Siteman study) where missing 25-28 teeth was associated with an increased risk of alveolar ridge compared to tongue cancer (aOR: 4.60; 95% CI: 1.97-11.10, P = .001). CONCLUSIONS: This study suggests an association between poor dental health and risk of alveolar ridge cancer independent of smoking, alcohol use, age, race, and sex. Future prospective and translational studies are needed to confirm this association and elucidate the mechanism of dental disease in alveolar ridge malignancies.

Microvascular Free Flap Outcomes in Maxillectomy Defects from Invasive Fungal Sinusitis.

OBJECTIVES: Microvascular free tissue transfer is routinely used for reconstructing midface defects in patients with malignancy, however, studies regarding reconstructive outcomes in invasive fungal sinusitis (IFS) are lacking. We aim to describe outcomes of free flap reconstruction for IFS defects, determine the optimal time to perform reconstruction, and if anti-fungal medications or other risk factors of an immunocompromised patient population affect reconstructive outcomes. METHODS: Retrospective review of reconstruction for IFS (2010-2022). Age, BMI, hemoglobin A1c, number of surgical debridements, and interval from the last debridement to reconstruction were compared between patients with delayed wound healing versus those without. Predictor variables for delayed wound healing and the effect of time on free flap reconstruction were analyzed. RESULTS: Twenty-seven patients underwent free flap reconstruction for IFS. Three patients were immunocompromised from leukemia and 21 had diabetes mellitus (DM). Patients underwent an average of four surgical debridements for treatment of IFS. The interval from the last IFS debridement to flap reconstruction was 5.58 months (±5.5). Seven flaps (25.9%) had delayed wound healing. A shorter interval of less than 2 months between the last debridement for IFS and reconstructive free flap procedure was associated with delayed wound healing (Fisher Exact Test p = 0.0062). Other factors including DM, BMI, HgA1c, and bone reconstruction were not associated with delayed wound healing. CONCLUSION: Patients with maxillectomy defects from IFS can undergo microvascular-free flap reconstruction with good outcomes while on anti-fungal medication. Early reconstruction in the first 2 months after the last IFS debridement is associated with delayed wound healing. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1642-1647, 2024.

Stacked fibula flap for unilateral total maxillectomy reconstruction with orbital preservation.

Unilateral total maxillectomy is indicated for locally advanced maxillary tumors that require complete removal of the midface bony structure and inferior orbital rim. Reconstruction of this defect is challenging due to aesthetic and functional concerns. A retrospective review of patients at two tertiary-care institutions undergoing unilateral total maxillectomy reconstruction with a stacked fibula flap from 2018 to 2022 was performed. Each patient's clinical course was reviewed, and attention was focused on the demonstration of surgical steps with photos. Twenty patients underwent stacked fibula flap reconstruction for unilateral total maxillectomy orbital preservation defects. Surgical extirpation was performed for malignancy (80%, 16/20) and for osteoradionecrosis or benign tumor in 20% (4/20). The complication rate was 30% (6/20). Most flaps survived (95%, 19/20). We present a modified, reproducible method of fibula flap reconstruction for unilateral total maxillectomy with orbital preservation that only requires two segments and maintains positive aesthetic and functional results.

Free Flap Outcomes for Head and Neck Surgery in Patients with COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) affects the vascular system, subjecting patients to a hypercoagulable state. This is of particular concern for the success of microvascular free flap reconstruction. This study aims to report head and neck free flap complications in patients with COVID-19 during the perioperative period. We believe these patients are more likely to experience flap complications given the hypercoagulable state. METHODS: This is a multi-institutional retrospective case series of patients infected with COVID-19 during the perioperative period for head and neck free flap reconstruction from March 2020 to January 2022. RESULTS: Data was collected on 40 patients from 14 institutions. Twenty-one patients (52.5%) had a positive COVID-19 test within 10 days before surgery and 7 days after surgery. The remaining patients had a positive test earlier than 10 days before surgery. A positive test caused a delay in surgery for 16 patients (40.0%) with an average delay of 44.7 days (9-198 days). Two free flap complications (5.0%) occurred with no free flap deaths. Four patients (10.0%) had surgical complications and 10 patients had medical complications (25.0%). Five patients (12.5%) suffered from postoperative COVID-19 pneumonia. Three deaths were COVID-19-related and one from cancer recurrence during the study period. CONCLUSION: Despite the heightened risk of coagulopathy in COVID-19 patients, head and neck free flap reconstructions in patients with COVID-19 are not at higher risk for free flap complications. However, these patients are at increased risk of medical complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 2023.

Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.

(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating immune cell proportions with clinical, pathologic, and genomic data. (3) Results: We reliably deconvolved 22 immune cell subtypes in most patients and found that the most common immune cell types were M0 macrophages, M2 macrophages, and memory resting CD4 T cells. In the multivariable analysis, we identified advanced N stage and the presence of γδ T cells as independently predictive of poorer survival. (4) Conclusions: We uncovered that γδ T cells in the tumor microenvironment were a negative predictor of survival among patients with untreated HNSCC. Our findings underscore the need to better understand the role of γδ T cells in HNSCC, including potential pro-tumorigenic mechanisms, and whether their presence may predict the need for alternative therapy approaches.

Neighborhood socioeconomic status and race are associated with incidence disparities in oral cavity cancers.

OBJECTIVES: To determine the association between neighborhood socioeconomic status (nSES), race and incidence rate trends of oral cavity cancer (OCC). MATERIALS AND METHODS: We used data from the SEER (Surveillance, Epidemiology, and End Results) 18 Census Tract-level SES and Rurality Database (2006-2018) database of the National Cancer Institute to create cohorts of OCC patients between 2006 and 2018. Annual incidence rates were calculated and trends in rates were estimated using joinpoints regression. RESULTS: The incidence of OCC is the highest among low nSES White Americans (2.86 per 100 000 persons) and the lowest among high nSES Black Americans (1.17 per 100 000 persons). Incidence has significantly increased among Asian Americans (annual percent change [APC]: low nSES-2.4, high nSES-2.6) and White Americans (APC: low nSES-1.4, high nSES-1.6). Significant increases in the incidence of oral tongue cancer in these groups primarily drive this increase. Other increases were noted in alveolar ridge cancer among White Americans and hard palate cancer among Asian Americans. OCC incidence decreased significantly in Hispanic Americans of high nSES (APC: -2.5) and Black Americans of low nSES (APC: -2.7). Floor of mouth cancer incidence decreased among most groups. CONCLUSION: Despite the overall decreasing incidence of OCC, these trends are inconsistent among all OCC subsites. Differences are seen by race, nSES, and subsite, indicating intersectional barriers that extend beyond nSES and race and ethnicity alone. Further research on risk factors and developing interventions targeting vulnerable groups is needed.

Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti-PD-1 in head and neck cancer.

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti-programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking. In a phase 2 trial (NCT02296684), we observed that 45% of patients treated with two doses of neoadjuvant pembrolizumab experienced marked pTRs (≥50%). Single-cell analysis of 17,158 CD8+ T cells from 14 tumor biopsies, including 6 matched pre-post neoadjuvant treatment, revealed that responding tumors had clonally expanded putative tumor-specific exhausted CD8+ tumor-infiltrating lymphocytes (TILs) with a tissue-resident memory program, characterized by high cytotoxic potential (CTX+) and ZNF683 expression, within the baseline TME. Pathologic responses after 5 weeks of PD-1 blockade were consistent with activation of preexisting CTX+ZNF683+CD8+ TILs, paralleling loss of viable tumor and associated tumor antigens. Response was associated with high numbers of CD103+PD-1+CD8+ T cells infiltrating pretreatment lesions, whereas revival of nonexhausted persisting clones and clonal replacement were modest. By contrast, nonresponder baseline TME exhibited a relative absence of ZNF683+CTX+ TILs and subsequent accumulation of highly exhausted clones. In HNSCC, revival of preexisting ZNF683+CTX+ TILs is a major mechanism of response in the immediate postneoadjuvant setting.

Targeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC.

The NFE2L2 (NRF2) oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion, and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry-based targeted proteomics assay based on internal standard-triggered parallel reaction monitoring to quantify 69 NRF2 pathway components and targets, as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved an existing internal standard-triggered parallel reaction monitoring acquisition algorithm, called SureQuant, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded HNSCCs, NRF2 signaling intensity positively correlated with NRF2-activating mutations and with SOX2 protein expression. Protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus infection status. CDKN2A (p16) protein expression positively correlated with the human papilloma virus oncogenic E7 protein and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or formalin-fixed paraffin-embedded archived tissues in under 90 min.

Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is an aggressive tumor with low response rates to frontline PD-1 blockade. Natural killer (NK) cells are a promising cellular therapy for T cell therapy-refractory cancers, but are frequently dysfunctional in patients with HNSCC. Strategies are needed to enhance NK cell responses against HNSCC. We hypothesized that memory-like (ML) NK cell differentiation, tumor targeting with cetuximab, and engineering with an anti-EphA2 (Erythropoietin-producing hepatocellular receptor A2) chimeric antigen receptor (CAR) enhance NK cell responses against HNSCC. EXPERIMENTAL DESIGN: We generated ML NK and conventional (c)NK cells from healthy donors, then evaluated their ability to produce IFNγ, TNF, degranulate, and kill HNSCC cell lines and primary HNSCC cells, alone or in combination with cetuximab, in vitro and in vivo using xenograft models. ML and cNK cells were engineered to express anti-EphA2 CAR-CD8A-41BB-CD3z, and functional responses were assessed in vitro against HNSCC cell lines and primary HNSCC tumor cells. RESULTS: Human ML NK cells displayed enhanced IFNγ and TNF production and both short- and long-term killing of HNSCC cell lines and primary targets, compared with cNK cells. These enhanced responses were further improved by cetuximab. Compared with controls, ML NK cells expressing anti-EphA2 CAR had increased IFNγ and cytotoxicity in response to EphA2+ cell lines and primary HNSCC targets. CONCLUSIONS: These preclinical findings demonstrate that ML differentiation alone or coupled with either cetuximab-directed targeting or EphA2 CAR engineering were effective against HNSCCs and provide the rationale for investigating these combination approaches in early phase clinical trials for patients with HNSCC.

Clinical outcomes following intraoperative pedicle disruption in fibula free flaps.

OBJECTIVES: Iatrogenic injury of the fibula free flap pedicle is rare. Postoperative flap survival and reconstructive outcomes following intraoperative pedicle severance are unknown. This study assesses free flap outcomes following accidental severance of the peroneal vessels. METHODS: Multi-institutional retrospective chart review from 2000 to 2020. RESULTS: Of 2975 harvested fibula free flaps, 26 had a history of pedicle severance during surgical reconstruction. Reasons for intraoperative pedicle severance included transection during muscular dissection 10/26 (39%), accidental severance with the bone saw 12/26 (46%), and other 4/26 (15.6%). The surgeon responsible for pedicle severance included residents 5/26 (19%), fellows 10/26 (39%), attendings 10/26 (39%), and unknown 1/26 (3.9%). The pedicle artery and vein were severed 10/26 (39%), artery 8/26 (31%), and vein 8/26 (31%). Truncated pedicle vessels were used 3/26 (11.7%), intraoperative anastomoses were performed 23/26 (89%). Postoperative revision in the OR within 7 days of surgery was required 6/26 (23%); 4 flaps were salvaged and 2 flaps failed, both arterial thrombosis. Flap failure was attributed to vascular thrombosis. Long-term flap survival and successful reconstructions were reported 24/26 (92%). CONCLUSION: Accidental severance of fibula free flap pedicle vessels can be corrected with intraoperative repair, without affecting long-term flap survival or reconstructive outcomes. Protecting the flap vessels while using the bone saw and during intramuscular dissection prevents accidental severance.

Lateral Skull Base and Auricular Reconstruction.

Reconstruction of the lateral temporal bone with adequate functional and cosmetic outcomes depends on a multidisciplinary approach including the head and neck surgeon, reconstructive surgeon, neurotologist, and anaplastologist. Approaching the defect includes consideration of the location, tissue type, function, and patient/tumor characteristics. Anatomic limitations due to prior therapy also play an important role in reconstructive choices. Here, we review contemporary literature regarding the reconstruction of this complex region.