Microvascular free tissue transfer in head and neck surgery has evolved through technological advancements, focusing on enhancing surgical outcomes and reducing complications. The strategic process involves preoperative planning for perforator mapping, intraoperative devices for microvascular anastomoses and patient positioning, and innovative postoperative monitoring techniques ensuring flap viability. This workflow has led to a high flap success rate, although revision surgery can still be necessary. This article aims to explore recent advances in microvascular free tissue transfer technology utilized across the preoperative, intraoperative, and postoperative domains for enhanced surgical efficacy.

OBJECTIVE:With increased nationwide emphasis on high-value care and cost reduction, more attention has been paid to postoperative outcomes. In this study, we examined if diagnosis related group (DRG) classifications could be used to predict total laryngectomy (TL) length of stay (LOS) which could help with determining areas for improved resource allocation. METHODS:This is a retrospective study at a single tertiary academic center of TL patients between January 2013 and December 2020. For each DRG, we compared the primary outcome of LOS and secondarily examined perioperative outcomes, including complications and readmissions. We used Kruskal-Wallis tests to assess perioperative outcome and LOS differences among DRGs' correlation. Furthermore, we used public data to determine annual geometric means LOS (GMLOS) for TLs and compared this to institutional LOS. RESULTS:The 211 patients were included. Patients with more severe DRG classification had greater LOS (p = 0.004). Fistula complications occurred at higher rates in more severe DRG classification, with major complication or comorbidity (MCC) at 25.0%, CC at 16.9%, and without complication or comorbidity (CC)/MCC at 3.1%, p = 0.02. The 30-day readmission was more common in MCC (26%) compared to CC (8.4%) or without CC/MCC (9.4%), p < 0.01. We found higher GMLOS compared to institutional LOS for TLs. CONCLUSION:TL patients with CC and MCC have longer LOS than those without CC/MCC, as well as higher fistula and readmission rates. DRGs can be used to identify areas to improve resource allocation for patients that may have poorer post-TL outcomes. LEVEL OF EVIDENCE: 3:

6061 Background: In several cancers, including head and neck squamous cell carcinoma (HNSCC), the immunosuppressive components of the tumor microenvironment (TME) can impact the effectiveness of immune checkpoint inhibitors (ICI). One significant component of the TME is the extracellular matrix, which is rich in collagen fibers. In this work we used machine learning and image analysis approaches on whole slide images (WSIs) to characterize collagen disorder architecture (CoDA) features and evaluated their association with outcomes in HNSCC patients receiving ICI. Methods: WSIs of HNSCC patients treated with ICI were obtained from University Hospitals (S1, n=43) and Emory University (S2, n=31). Tiles from the tumor annotated regions of the WSIs were extracted, and a derivative-of-Gaussian model was used to identify collagen fibers in the stroma of these tiles. Various CoDA features were then calculated as follows: (1) collagen fiber fragmentation measure, (2) collagen fiber bundling percentage, (3) collagen fiber rigidity measure, (4) collagen fiber anisotropy index and (5) collagen fiber density index. CoDA features of S1and S2 were combined and split into 50:50 for training and validation. For survival analysis using overall survival (OS) as endpoint, the median risk score in the training set was applied for risk stratification in the validation set by means of a Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression model. For predictive analysis, CoDA features from patients with objective response (OR) to ICI were identified (S1, non-responder=23, responder=20), (S2, non-responder=23, responder=8). The top features were then selected using the LASSO and combined with a Generalized Linear Model classifier. A 5-fold cross-validation assessed Area Under the Receiver Operating Characteristics Curve (AUC) for predicting OR, with average AUC as the final performance metric in the validation set. Results: For survival analysis, high risk patients in the validation set had worse survival than low risk patients (HR=2.7 (95% CI=1.1-6.6, p=0.02)). For predicting OR, the selected top CoDA features were collagen fiber fragmentation measure, collagen fiber bundling percentage, collagen fiber rigidity measure and collagen fiber density index and the average AUC was 0.64±0.16. More fragmentation of the collagen fibers along with dense thick bundles and straightened fibers were observed in the WSIs of non-responder patients to ICI. Conclusions: High risk CoDA features correlated with worse survival in patients with HNSCC receiving ICI. Also, we established a correlation of specific CoDA features with OR to ICI. The prognostic and predictive value of CoDA deserves additional exploration with confirmatory data from larger, independent multi-site validation.

BACKGROUND:Facial paralysis is a life-altering condition that may arise from various etiologies, ranging from trauma to malignancy. Permanent facial paralysis may occur secondary to facial nerve sacrifice or irreversible damage to the nerve. In these particularly devastating cases, protection and maintaining function of the eye is paramount. There are many effective lagophthalmos corrective surgical procedures available for these patients. While placement of eyelid weights and lid tightening surgeries are the cornerstone of eyelid rehabilitation, limited information exists on whether the timing of eyelid interventions in the setting of permanent facial paralysis impact outcomes, including need for revision surgery. METHODS:A single-center retrospective chart review was performed for patients with irreversible facial paralysis treated with an upper eyelid weight between 2013 to 2022. Electronic health records were acquired to obtain facial paralysis etiology, associated clinical characteristics, the type of intervention, and the timing of intervention. Patients were classified as immediate if the eyelid weight operation occurred within 29 days of the initial facial paralysis and delayed if the surgery occurred 30 days or more after initial presentation. Outcomes were assessed in terms of revision procedures and surgical complications. RESULTS:There were 70 patients in total, with 35 patients in the immediate category and 35 patients in the delayed category. The most common etiology related to parotid gland pathology, and 58.6% of patients had facial paralysis from cancer-related surgeries. There were no significant differences in revision rates (p < 0.208) or in the types of procedures (p = 0.077) between the two groups. The complication rates also did not differ significantly between groups; however, there were only complications in the delayed intervention group. CONCLUSIONS:These findings suggest there is no difference in postoperative complications between groups, including the need for revision surgeries when comparing groups with immediate or delayed intervention. Thus, treatment plans should be customized based on patient and provider preferences.

Head and neck squamous cell carcinoma (HNSCC) outcomes remain stagnant, in part due to a poor under-standing of HNSCC biology. The importance of tumor heterogeneity as an independent predictor of outcomes and treatment failure in HNSCC has recently come to light. With this understanding, 3D culture systems, including patient derived organoids (PDO) and organotypic culture (OTC), that capture this heterogeneity may allow for modeling and manipulation of critical subpopulations, such as p-EMT, as well as interactions between cancer cells and immune and stromal cells in the microenvironment. Here, we review work that has been done using PDO and OTC models of HNSCC, which demonstrates that these 3D culture models capture in vivo tumor het-erogeneity and can be used to model tumor biology and treatment response in a way that faithfully recapitulates in vivo characteristics. As such, in vitro 3D culture models represent an important bridge between 2D monolayer culture and in vivo models such as patient derived xenografts.

PDF file, 2045KB, Patient tumor characteristics (Group 2).

Supplemental Figure S1. Levels of serum cytokines in patients over the course of treatment. Serum levels of the cytokines IFN-γ (A), IP-10 (B), TNF-α (C) MIP-1α (D), MIP-1β (E), RANTES (F), GM CSF (G), and IL-8 (H) were measured at baseline and during cycle 8 using a custom V-Plex assay. Assay was performed in triplicate and the average was plotted for each individual patient. *, p=0.0008 for IFN-γ, p=0.0011 for IP-10, p=0.0102 for TNF-α Supplemental Figure S2. Levels of serum cytokines in patients stratified by length of progression-free survival. Serum levels of the cytokines MIP-1α (A), MIP-1β (B), RANTES (C), GM-CSF (D), and IL-8 (E) were measured at baseline and during cycle 8 using a custom V-Plex assay. The assay was performed in triplicate and the average was plotted for each individual patient stratified by progression-free survival greater than or less than 100 days Supplemental Figure S3. Gating strategy for defining monocytic and granulocytic MDSC. Examples of monocytic-dominant (A) and granulocytic-dominant (B) total MDSC. PBMCs procured from pre-therapy blood draws were stained with anti-CD33-APC, anti-HLA-DR-PECy7, anti-CD11b-PE, anti-CD14-V-450, and anti CD15-FITC antibodies; CD33+/HLA-DR- populations were further characterized by CD15, CD14, and CD11b expression. Percentages gleaned from CD15+CD11b+ and CD14+CD11b+ quadrants were back multiplied by total MDSC (CD33+HLA-DR-) to obtain values presented in Table S3.

PDF file, 46K, Quantification of color coded Ktrans and ve parametric images following DCE-MRI.

PDF file, 1581KB, HNSCC cell line characteristics.

PDF file, 5124KB, YM155 and cisplatin combination treatment significantly inhibits tumor cell motility. Tumor cell motility was examined by scratch assay.

PDF file, 839KB, YM155 and cisplatin combination treatment significantly inhibits tumor cell proliferation. UM-SCC-74A cells were treated with YM155 or cisplatin (CDDP) alone or in combination. After 72 hrs, cell proliferation was assessed by MTT assay.

Background Fibula free flaps (FFF) are often considered the first choice for mandibular reconstruction, but scapular system free flaps (SFF) have increased in popularity due to versatility, donor site advantages, and patient factors. Methods Retrospective chart review of patients undergoing mandibulectomy with FFF or SFF reconstruction from 2016 to 2021. Results Hundred and seventy-six patients (FFF n = 145, SFF n = 31) underwent the aforementioned procedures. Mean FFF operative time was 9.47 h versus 9.88 for SFF (p = 0.40). Two-flap reconstructions required 12.65 h versus 10.09 for SFF with soft tissue (p = 0.002). Donor site complications were identified in 65.6% of FFF with skin grafting. Conclusions These findings suggest that SFF requires similar operative time and results in reduced donor site morbidity as compared to FFF. Supine, concurrent harvesting of SFF allows for single-flap harvest with significantly shorter operative time. SFF could be considered a primary option for mandible reconstruction for complex defects and in select patients.

PDF file, 96K, HSV-1 immuno stained sections of subcutaneous and intracranial tumors treated with PBS or ATN-224 (0.7mg) by daily gavage.

OBJECTIVES:Laryngeal and hypopharyngeal cancers treated with total laryngectomy (TL) may provide a unique avenue for COVID-19 to infect cancer patients. The objective of this investigation was to identify incidence of COVID-19 infection and potential complications in TL patients. MATERIALS AND METHODS:Data was extracted from TriNetX COVID-19 research network from from 2019 to 2021 and ICD-10 codes were utilized to query for laryngeal or hypopharyngeal cancer, and outcomes of interest. Cohorts were propensity score-matched based on demographics and co-morbidities. RESULTS:A query of active patients in TriNetX from January 1, 2019 to December 31, 2021 identified 36,414 patients with laryngeal or hypopharyngeal cancer out of the 50,474,648 active patients in the database. The overall COVID-19 incidence in the non-laryngeal or hypopharyngeal cancer population was 10.8% compared to 18.8% (p < 0.001) in the laryngeal and hypopharyngeal cancer group. Those who underwent TL had a statistically significant increased incidence of acquiring COVID-19 (24.0%) when compared to those without TL (17.7%) (p < 0.001). TL patients with COVID-19 had a higher risk of developing pneumonia RR (risk ratio) 1.80 (1.43, 2.26), death 1.74 (1.41, 2.14), ARDS 2.42 (1.16, 5.05), sepsis 1.77 (1.37, 2.29), shock 2.81 (1.88, 4.18), respiratory failure 2.34 (1.90, 2.88), and malnutrition 2.46 (2.01, 3.01) when matched with those COVID-19 positive cancer patients without TL. CONCLUSIONS:Laryngeal and hypopharyngeal cancer patients had a higher rate of acquiring COVID-19 than patients without these cancers. TL patients have a higher rate of COVID-19 compared to those without TL and may be at a higher risk for sequalae of COVID-19.

Purpose: To analyze the impact of demographic, clinical, and management variables on time to treatment initiation (TTI) and overall survival (OS).Study design: Retrospective chart review.Materials and methods: Medical records of patients diagnosed with head and neck cancer from 2018 to 2020 were reviewed. Univariate linear and Cox-regressions identified predictors of TTI and OS. Kaplan Meier (KM) curves assessed the difference in survival by diagnostic year and TTI.Results: 381 patients met eligibility criteria. Median TTI was 35.0 days (IQR: 25.0-49.0). Only 10.8 % of all patients reported any treatment delay, with TTI exceeding 90 days found in 3.7 % of patients. TTI increased with African American race (p = 0.02), ED referrals (p = 0.02), and direct admission status (p = 0.01). When compared to treatment with surgery alone, TTI was shorter in patients undergoing surgery with adjuvant radiation (p = 0.02), adjuvant chemoradiation (p = 0.04), and salvage surgery (p = 0.04). Univariate Coxregressions found smoking (p = 0.01), direct admission status (p = 0.02), increased duration of symptoms (p = 0.02), placement of PEG tubes (p < 0.01) and tracheostomies (p < 0.01), combination treatment (p < 0.01), and surgery with adjuvant chemoradiation treatment (p = 0.01) to increase mortality risk. Disease characteristics, including tumor size (p < 0.01), presence of nodal disease (p = 0.02), and late-stage disease (p < 0.01), increased mortality risk. TTI and diagnostic year did not impact survival.Conclusions: Our analysis determined several demographic, referral, and treatment factors impacted TTI. However, increased TTI did not impact survival. Characteristics consistent with advanced disease worsened OS. Despite the pandemic burden, patients diagnosed in 2020 showed no difference in short-term survival compared to prior years.