Prolonged operative time predicts postoperative deep venous thrombosis in head and neck cancer patients who undergo free flap reconstruction.

Objective: This study sought to quantify the deep venous thrombosis (DVT) incidence in head and neck cancer (HNC) patients undergoing free tissue transfer and to identify independent predictors of postoperative DVT. Materials and Methods: This is a cross-sectional study of the National Surgical Quality Improvement Program database from 2010 through 2020. The sample included all HNC surgical patients treated with free flap reconstruction. The study outcome was the presence of a DVT requiring treatment within 30 days of surgery. Univariate analyses were performed using chi-squared and independent t-tests. A multiple logistic regression model was created using all significant univariate predictors. Results: A total of 3954 patients were identified, of whom 53 (1.3%) experienced a postoperative DVT. The only medical comorbidity associated with DVT was COPD (RR = 2.7 [1.3, 5.4]; p < .01). Operative time longer than 9 hours (RR = 1.9 [1.0, 3.2]; p = .04) and length of stay longer than 10 days (RR = 1.9 [1.1, 3.2]; p = .02) were associated with greater DVT rates. In the multivariate analysis, only COPD (p < .01) and operative time (p = .02) were independently associated with DVT risk. The presence of a DVT was found to increase the relative risk of readmission (RR = 2.1 [1.2, 3.6]; p < .01) and non-home disposition (RR = 2.4 [1.7, 3.5]; p < .01). Conclusions: The incidence of DVT in HNC free flap patients was comparable to what has been reported in the general population of HNC surgery patients. Operative time >9 h and COPD history were independent risk factors for DVT in this subset of patients. Symptomatic DVTs necessitating treatment were accompanied by poorer post-hospitalization outcomes. Level of Evidence: Level 3.

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.

Post-operative Outcomes in Pediatric Patients Following Facial Reconstruction With Fibula Free Flaps.

EDUCATIONAL OBJECTIVE: Assess outcomes of pediatric facial reconstruction with fibula free flaps. OBJECTIVES: Free flap reconstruction of complex maxillofacial defects in pediatric patients is rare. Post-operative complications, donor site morbidity, impact on craniofacial growth, and oro-dental rehabilitation are unknown. Our study assesses the outcomes of pediatric maxillofacial reconstruction with composite fibula free flaps. STUDY DESIGN: Retrospective chart review. METHODS: Multi-institutional retrospective chart review from 2000 to 2020 on pediatric patients undergoing maxillomandibular reconstruction with fibula free flaps. RESULTS: Eighty-seven patients underwent 89 surgeries; 5 maxillary and 84 mandibular defects. Median age: 12 years. Defects were acquired following resection of sarcoma/carcinoma 44% or benign tumors 50%. 73% of cases had immediate free flap reconstruction. Closing osteotomies were reported in 74%; 1 in 40%, 2 in 27%, and more than 2 in 6.7%. Hardware was used in 98% and removed in 25%. 9.2% demonstrated long-term hardware exposure, greater than 3 months following reconstruction. Short-term complications: wound infection 6.7%, flap salvage/failure 2.2%, fistula 1.1%, and compromised craniofacial growth: 23%. Two patients developed trismus. Long-term fibula donor site complications: hypertrophic scarring: 3.4%, dysesthesia: 1.1%, and long-term gait abnormality: 1.1%. Dental rehabilitation was performed in 33%. Post-operative speech outcomes showed 94% with fully intelligible speech. CONCLUSION: Pediatric maxillary and mandible defects repaired with fibula free flaps demonstrated complication rates comparable to the adult free flap population. Long-term follow-up did not demonstrate adverse outcomes for craniofacial growth. Hardware for flap retention was utilized and remained in place with minimal exposure. Post-operative gait abnormality is rare. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:302-306, 2023.

The Role of Fluorescent Angiography in Free Flap Reconstruction of the Head and Neck.

OBJECTIVES: Highlight the use of fluorescent angiography in free flap reconstruction of the head and neck. Qualify how fluorescent angiography can be selectively added to management paradigms for head and neck free flap reconstruction. METHODS: Retrospective chart review of 993 free flaps completed from the time the SPY Elite® system first became available at our institution between September 2013, until August 2020. Cases that used the SPY Elite® system were grouped into three broad categories: evaluation during initial flap harvest while still attached to the donor site, evaluation after anastomosis in the head and neck area, and evaluation post-operatively for questionable flap viability. RESULTS: The SPY Elite® system was used in 64 cases. Forty flaps were evaluated intraoperatively during initial harvest and before anastomosis to the head and neck area. Of these, 20 had signs of poor perfusion of the entire skin paddle, 12 had large myogenous or skin flaps with questionable perfusion of the distal aspect, and 8 were evaluated for other reasons. In this group the use of SPY Elite® changed the management of the patient in 20 cases (50%). Ten flaps were evaluated intraoperatively after anastomosis to the head and neck to ascertain adequate flow to the entire flap. In this group management was changed in two (20%). Fourteen flaps were evaluated 3-5 days post operatively due to suspected failure of a component. In five cases (36%), the use of SPY Elite® determined management with either trimming or discarding the flap. CONCLUSION: Assessment of flap perfusion via fluorescent angiography during initial flap harvest or when flap compromise is suspected post-operatively can guide decision making in free flap reconstruction of the head and neck and can be added to existing planning and management paradigms. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1388-1393, 2023.

The Safety and Efficacy of Tracheostomy in Patients Diagnosed With COVID-19: An Analysis of 143 Patients at a Major NYC Medical Center.

OBJECTIVE: To determine the optimal surgical strategy for performing tracheostomy in COVID-19 patients. BACKGROUND: Many ventilated COVID-19 patients require prolonged ventilation. We do not know if tracheostomy will improve their care. Given the paucity of data on this topic, the optimal surgical approach has yet to be elucidated. METHODS: This is a cohort study of 143 ventilator dependent COVID-19 patients undergoing tracheostomy at an academic medical center from April 15th to May 15th, 2020, with follow up until June 1, 2020. We included adult patients admitted to a NYC medical center with COVID-19 who required invasive mechanical ventilation for greater than 2 weeks who were unable to be extubated and determined to have reasonable chance of recovery and fit defined tracheostomy candidate criteria. Patients underwent either a percutaneous tracheostomy (PT) or open surgical tracheostomy (ST) performed by 1 of 3 surgical services. RESULTS: One hundred forty-three patients underwent tracheostomy, 58 (41%) via a ST, and 85 (59%) via a PT. There were no significant differences in patient characteristics between the 2 groups, except that more patients who had a history of extracorporeal membrane oxygenation underwent PT (11% vs 2%, P = 0.049). There were no statistical differences observed between the PT and ST groups with regard to bleeding complications (3.5%vs 10.3%, P = 0.099), tracheostomy related complications (5.9% vs 8.6%, P = 0.528), inpatient death (12% vs 5%, P = 0.178), discharge from hospital (39% vs 36%, P = 0.751) or surgeon illness (0% vs 0%, P = 1). CONCLUSION AND RELEVANCE: The rapid formation of a multi-disciplinary team allows for the efficient evaluation and performance of a large volume of tracheostomies in a resource-limited setting. Bedside tracheostomy in COVID-19 does not cause additional harm to patients if performed after 2 weeks from intubation. It also seems to be safe for proceduralists to perform in this timeframe. The manner of tracheostomy does not change outcomes significantly if it is performed safely and efficiently.

Conditional and Overall Disease-Specific Survival in Patients With Paranasal Sinus and Nasal Cavity Cancer: Improved Outcomes in the Endoscopic Era.

BACKGROUND: The management of paranasal sinus and nasal cavity malignancies has evolved significantly with the development of advanced endoscopic techniques and improvements in adjuvant therapy. We sought to characterize both disease-specific survival (DSS) and 5-year conditional disease-specific survival (CDSS, the change in life expectancy with increasing survivorship) for sinus malignancies diagnosed before and after the year 2000. METHODS: Patients diagnosed with sinus and nasal cavity cancer between 1973-2015 were extracted from the Surveillance, Epidemiology, End Results (SEER) registry. Kaplan-Meier analysis for DSS was stratified by year of diagnosis before and after 2000. Cox-proportional hazards models of DSS controlling for stage, age, and year of diagnosis were generated. CDSS was calculated using Cox-regression models stratified by stage. RESULTS: We analyzed 10,535 patients. Diagnosis after the year 2000 was independently associated with improved DSS (HR:0.81, 95% CI: 0.75-0.87, P < .001) after controlling for age and stage. After stratifying by stage, diagnosis after year 2000 was associated with improved DSS for localized (HR:0.71, 0.59-0.86, P < .001) malignancies, regional (HR: 0.86, 0.78-0.94, P = .001) and distant malignancies (HR 0.74, 0.63-0.87, P < .001). CDSS improved with increasing survivorship for all stages of sinus and nasal cavity cancer, and those diagnosed after 2000 had improved CDSS compared to those diagnosed before 2000. Descriptively, the association of year of diagnosis with CDSS diminished with increasing survivorship for localized cancers, but was consistent for other stages. CONCLUSION: For paranasal sinus and nasal cavity malignancies, year of diagnosis independently influences both DSS and CDSS. Improved survival is likely due to advances in both surgical and adjuvant treatments. To our knowledge, this study is the first to examine CDSS for these malignancies.

Targeted Neoadjuvant Intra-arterial Chemotherapy in Lacrimal Gland Adenoid Cystic Carcinoma: A Histological Correlation Using Apoptotic Tumor Markers.

Neoadjuvant intra-arterial cytoreductive chemotherapy is used for the treatment of lacrimal gland adenoid cystic carcinomas (ACC) to improve outcomes in this condition with an otherwise dismal prognosis. We share our experience in the management of an advanced case of ACC using a novel, highly targeted intra-arterial cytoreductive chemotherapy delivery technique involving both the internal and external carotid circulation, with an attempt to correlate the effect histologically. Refinement of the chemotherapy delivery using the tumor's vascular anatomy and appropriate blood vessel selection may lead to future globe sparing procedures without compromising survival.

MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma.

We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into "early-stage" by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only (p < 0.001); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2-0.6; p=0.0005). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls (p < 0.0005). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients.

Venous Flow Coupler in Head and Neck Free Flap Reconstruction.

OBJECTIVE: To describe the utility of venous flow couplers in monitoring free tissue flaps in the immediate postoperative setting. STUDY DESIGN: Retrospective case series. SETTING: Otolaryngology department at a single tertiary care institution. METHODS: A retrospective case series of free flap reconstructions in which venous flow couplers were employed to supplement flap monitoring. All free flap cases performed over the past 4 years were reviewed. Inclusion criteria were venous flow coupler and arterial flow Doppler monitored for 5 days postoperatively. RESULTS: From July 2014 through May 2018, the venous flow coupler was used with the arterial flow Doppler and clinical monitoring in 228 cases. Eleven cases did not meet criteria for inclusion; thus, 217 cases were analyzed. Twenty cases (9.2%) returned to the operating room with concern for flap compromise, and 16 were salvaged. The combination of venous flow coupler and arterial flow Doppler identified 19 of these flaps. Venous flow couplers identified 5 compromised flaps before there was an arterial signal change, and all were salvaged. Additionally, there was a 24.1% false-positive rate when 2 venous flow couplers were used in parallel. For the venous flow coupler, the positive predictive value was 64.3% and the negative predictive value, 98.9%. The false-positive rate in the series was 5.1%. The sensitivity was 90% and the specificity, 94.9%. CONCLUSION: The venous flow coupler is able to detect venous thrombosis in the absence of arterial thrombosis and may contribute to improved flap salvage rates.

A novel neck brace to characterize neck mobility impairments following neck dissection in head and neck cancer patients.

Objective: This article introduces a dynamic neck brace to measure the full range of motion (RoM) of the head-neck. This easy-to-wear brace was used, along with surface electromyography (EMG), to study changes in movement characteristics after neck dissection (ND) in a clinical setting. Methods: The brace was inspired by the head-neck anatomy and was designed based on the head-neck movement of 10 healthy individuals. A 6 degrees-of-freedom open-chain structure was adopted to allow full RoM of the head-neck with respect to the shoulders. The physical model was realized by 3D printed materials and inexpensive sensors. Five subjects, who underwent unilateral selective ND, were assessed preoperative and postoperative using this prototype during the head-neck motions. Concurrent EMG measurements of their sternocleidomastoid, splenius capitis, and trapezius muscles were made. Results: Reduced RoM during lateral bending on both sides of the neck was observed after surgery, with a mean angle change of 8.03° on the dissected side (95% confidence intervals [CI], 3.11-12.94) and 9.29° on the nondissected side (95% CI, 4.88-13.69), where CI denotes the confidence interval. Axial rotation showed a reduction in the RoM by 5.37° (95% CI, 2.34-8.39) on the nondissection side. Neck extension showed a slight increase in the RoM by 3.15° (95% CI, 0.81-5.49) postoperatively. Conclusions: This brace may serve as a simple but useful tool in the clinic to document head-neck RoM changes in patients undergoing ND. Such a characterization may help clinicians evaluate the surgical procedure and guide the recovery of patients.

Shift in the timing of microvascular free tissue transfer failures in head and neck reconstruction.

OBJECTIVE: Analyze the cause and significance of a shift in the timing of free flap failures in head and neck reconstruction. STUDY DESIGN: Retrospective multi-institutional review of prospectively collected databases at tertiary care centers. METHODS: Included consecutive patients undergoing free flap reconstructions of head and neck defects between 2007 and 2017. Selected variables: demographics, defect location, donor site, free flap failure cause, social and radiation therapy history. RESULTS: Overall free flap failure rate was 4.6% (n = 133). Distribution of donor tissue by flap failure: radial forearm (32%, n = 43), osteocutaneous radial forearm (6%, n = 8), anterior lateral thigh (23%, n = 31), fibula (23%, n = 30), rectus abdominis (4%, n = 5), latissimus (11%, n = 14), scapula (1.5%, n = 2). Forty percent of flap failures occurred in the initial 72 hours following reconstruction (n = 53). The mean postoperative day for flap failure attributed to venous congestion was 4.7 days (95% confidence interval [CI], 2.6-6.7) versus 6.8 days (CI 5.3-8.3) for arterial insufficiency and 16.6 days (CI 11.7-21.5) for infection (P < .001). The majority of flap failures were attributed to compromise of the arterial or venous system (84%, n = 112). Factors found to affect the timing of free flap failure included surgical indication (P = .032), defect location (P = .006), cause of the flap failure (P < .001), and use of an osteocutaneous flap (P = .002). CONCLUSION: This study is the largest to date on late free flap failures with findings suggesting a paradigm shift in the timing of flap failures. Surgical indication, defect site, cause of flap failure, and use of osteocutaneous free flap were found to impact timing of free flap failures. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:347-353, 2020.

Outcomes and cost implications of microvascular reconstructions of the head and neck.

BACKGROUND: Critical review of current head and neck reconstructive practices as related to free flap donor sites and their impact on clinical outcomes and cost. METHODS: Retrospective multicenter review of free tissue transfer reconstruction of head and neck defects (n = 1315). Variables reviewed: defect, indication, T classification, operative duration, and complications. A convenience sample was selected for analysis of overall (operative and inpatient admission) charges per hospitalization (n = 400). RESULTS: Mean charges of hospitalization by donor tissue: radial forearm free flap (RFFF) $127 636 (n = 183), osteocutaneous RFFF (OCRFFF) $125 456 (n = 70), anterior lateral thigh $133 781 (n = 54), fibula $140 747 (n = 42), latissimus $208 890 (n = 24), rectus $169 637 (n = 18), scapula $128 712 (n = 4), and ulna $110 716 (n = 5; P = .16). Mean operative times for malignant lesions stratified by T classification: 6.9 hours (±25 minutes) for T1, 7.0 hours (±16 minutes) for T2, 7.3 hours (±17 minutes) for T3, and 7.8 hours (±11 minutes) for T4 (P < .0001). Complications correlated with differences in mean charges: minor surgical ($123 720), medical ($216 387), and major surgical ($169 821; P < .001). Operations for advanced malignant lesions had higher mean charges: T1 lesions ($106 506) compared to T2/T3 lesions ($133 080; P = .03) and T4 lesions ($142 183; P = .02). On multivariate analysis, the length of stay, operative duration, and type a postoperative complication were factors affecting overall charges for the hospitalization (P < .018). CONCLUSION: Conclusion: The RFFF and OCRFFF had the lowest complication rates, length of hospitalization, duration of operation, and mean charges of hospitalization. Advanced stage malignant disease correlated with increased hospitalization length, operative time, and complication rates resulting in higher hospitalization charges.

Combined endoscopic and transcervical approach for free flap reconstruction of nasopharyngeal and clival defects: A case report.

We report a case during which a new method of reconstruction for a nasopharyngeal and skull base defect was successfully performed. A 45-year-old female with granulomatosis with polyangiitis presented with computed tomography (CT) findings demonstrative of chronic clival and cervical spine osteomyelitis secondary to nasopharyngeal destruction. The posterior nasopharyngeal defect, evident as a wide area of mucosal erosion exposing the clivus centrally, was successfully reconstructed with an anterior serratus muscle-free tissue transfer via both transcervical and endoscopic transnasal approaches utilizing a laparoscopic fixation device, a previously unreported method for free flap inset, to secure the free flap. The patient tolerated this well and no major complications were encountered. At 2-year follow-up, the patient was without signs of cerebrospinal fluid leak or sequelae of infectious complications, including meningitis and osteomyelitis. A combined transcervical and endoscopic transnasal approach using a laparoscopic fixation device for free flap inset can be an effective method to reconstruct posterior nasopharyngeal defects in those patients whom local reconstructive options are not available.

Transoral robotic retropharyngeal node dissection in oropharyngeal squamous cell carcinoma: Patterns of metastasis and functional outcomes.

BACKGROUND: Assessment of the retropharyngeal lymph nodes is essential in the treatment for oropharyngeal squamous cell carcinoma (SCC). Transoral robotic retropharyngeal lymph node dissection (RPLND) may provide valuable staging information and guide selection of adjuvant therapy in a transoral robotic surgery (TORS) treatment paradigm. METHODS: Outcomes were compared between 30 patients with oropharyngeal SCC with tonsillar primaries undergoing RPLND and 37 stage-matched cases without RPLND. RESULTS: Retropharyngeal metastasis was confirmed in 6 patients undergoing RPLND. Compared with 37 stage-matched controls, there were no differences in length of stay, length of feeding tube dependence, net change in perioperative weight, or rates of hemorrhage and postoperative complications. RPLND altered adjuvant treatment recommendations in 1 of 30 patients. CONCLUSION: RPLND is technically feasible by a purely transoral robotic approach. Its performance is not associated with worse swallowing outcomes or rates of complication. In select patients, RPLND may provide valuable staging information and guide the selection of adjuvant therapy.

A randomized controlled trial of corticosteroids for pain after transoral robotic surgery.

OBJECTIVE: To determine if an extended perioperative course of corticosteroids will improve pain control following transoral robotic surgery (TORS). STUDY DESIGN: Randomized, double-blind, placebo-controlled trial. METHODS: Patients undergoing TORS for initial treatment of oropharyngeal squamous cell carcinoma received a single intraoperative dose of 10-mg dexamethasone and then were randomized to receive 8-mg dexamethasone every 8 hours, or placebo, for up to 4 days after surgery. Pain, measured by visual analog scale (VAS), was the primary outcome measure. Secondary outcome measures included length of stay, dysphagia assessments, and complications. RESULTS: VAS pain scores were similar between steroid and placebo cohorts on postoperative day (POD) 1, 2, and 7 through 21, although they significantly improved in the steroid cohort on POD 3. The steroid cohort also demonstrated a decreased hospital length of stay (median 1 day) and improvement in diet consistency, as measured by the performance status scale on POD 7 through 21. There was no difference in complications between the steroid and placebo cohorts. CONCLUSION: Extended perioperative corticosteroids after TORS is safe and may allow earlier improvement in diet consistency and decreased length of hospital stay, although postoperative pain appears minimally affected. LEVEL OF EVIDENCE: 1b. Laryngoscope, 127:2558-2564, 2017.