Depth of invasion as an independent prognostic factor in early-stage oral cavity squamous cell carcinoma.

PURPOSE: To determine the significance of depth of invasion as a predictor of recurrence and mortality in tongue and non-tongue early-stage oral cavity squamous cell carcinoma patients treated with surgery and no postoperative radiotherapy. MATERIALS AND METHODS: 344 patients with oral cavity squamous cell carcinoma from 2005 to 2022 at a tertiary academic medical center were reviewed. Patients were included if they had newly diagnosed, previously untreated T1-T2N0 disease treated with surgery alone that was observed within a follow-up of 5 years. For each patient, anatomic site of oral cavity squamous cell carcinoma was categorized as either tongue or non-tongue. Cox proportional hazards regression analyses were performed to determine the association of depth of invasion with recurrence and mortality, with anatomic site, smoking status, and age at biopsy as covariates. Model assumptions were tested by statistical and graphical evaluation using Schoenfeld residuals. RESULTS: Of 108 patients with T1-T2N0 disease, 78 (72.2 %) had tongue disease, and 30 (27.8 %) had non-tongue disease. Median follow-up was 18.2 months (range, 0.01-58.2 months). In the Cox proportional hazards models, with adjustment for anatomic site and other covariates, depth of invasion positively predicted recurrence (HR 1.16, 95 % CI: 1.01-1.32, p = 0.034) and death (HR 1.42, 95 % CI: 1.11-1.83, p = 0.006). CONCLUSIONS: Depth of invasion is an independent predictor of recurrence and death across early-stage tongue and non-tongue squamous cell carcinoma. Therefore, depth of invasion may indicate a need for more aggressive treatment than surgery alone, such as postoperative radiotherapy, even in the absence of other adverse features on pathology within the early-stage population.

Characterizing Long-Term Swallowing and Voice Outcomes Following Anterior Transcervical Approach.

OBJECTIVES: (1) Assess the frequency and severity of long-term swallowing and voice complaints, follow-up care, risk factors for the development of long-term swallowing and voice complications in patients who underwent anterior transcervical approach (ACA). (2) Determine incidence of long-term swallowing and voice complications requiring follow-up otolaryngologic care and assess the frequency of otolaryngologic follow-up for postoperative swallowing and voice complaints. METHODS: Retrospective cohort study of patients between January 2017 and March 2020 who underwent ACA. Demographic information, data from preoperative evaluation, operative records, and data from postoperative visits were collected. Patients were contacted to complete the Eating Assessment Tool and the "Impairment" subset of the Voice Symptoms Scale. RESULTS: A total of 48 patients (10.6%) followed up with a head and neck surgeon for swallowing complaints and 31 patients (6.8%) for voice complaints. Otolaryngology follow-up for swallowing complaints among patients with at least 3 and 12 months of follow-up was 16.4% and 17.8%, respectively. Otolaryngology follow-up for voice complaints among patients with at least 3 and 12 months of follow-up was 11.7% and 11.9%, respectively. Swallowing function was abnormal in 40.7% at least 3 months after surgery and in 41.8% 12 months after. Voice function was abnormal in 55.7% of respondents at least 3 months after surgery and in 54.5% of respondents 12 months after. CONCLUSIONS: ACA is associated with otolaryngologic complications that include dysphagia and dysphonia. This study demonstrates that long-term swallowing and voice dysfunction appear to persist longer than what is noted by patient utilization of follow-up otolaryngologic care. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3201-3205, 2024.

Use of Banked Fibula for Improved Nasal Reconstruction Following Free Fibula Midface Reconstruction.

OBJECTIVE: Anterior maxillary deficiency caused by trauma or oncologic resection presents a complex reconstructive challenge. The authors present a technique for 2-stage midface reconstruction utilizing a vascularized free fibula flap for maxillary reconstruction, followed by nasal reconstruction at a second stage utilizing a banked fibula graft. METHODS: This case series utilizes a 2-stage technique for midface reconstruction. In the first stage, a fibula-free flap was used to reconstruct the maxilla with the excess banked in the abdomen. In the second stage, this bone graft was used to restore the nasal dorsum. RESULTS: Two patients were included in this series. Patient 1 was a 28-year-old man who presented after a remote gunshot wound to his face, resulting in complete loss of his anterior maxilla and nasal support with midface collapse. Patient 2 was a 65-year-old man who presented with squamous cell carcinoma of the hard palate with extension into the maxilla and nasal septum. In both cases, the flaps healed without complication, providing midface restoration. Placement of the banked fibula graft in a second stage resulted in restoration of dorsal nasal projection. CONCLUSION: The authors describe the use of "spare" fibula parts for nasal reconstruction after loss of the maxilla and cartilaginous septum. The use of the fibula bone as a graft to restore the nasal dorsum in a delayed manner allows for a better assessment of the esthetic needs after the massive swelling from the initial surgery has abated. Further, this approach eliminates the need for a second donor site for nasal reconstruction.

Financial (dis)incentives to surgical management of head and neck cancer care.

BACKGROUND: Patients with head and neck cancer (HNC) often require complex surgical reconstruction. This retrospective, cross-sectional study compares financial factors influencing HNC and breast cancer (BC) care to examine care disparities. METHODS: Pricing data from 2012 to 2021 was abstracted from the CMS Physician Fee Schedule Look-Up Tool. Nonprofit and research support was quantified by searching the NIH, IRS, and GuideStar databases. New York State Department of Health data from 2015 to 2019 was analyzed to compare costs, charges, and payer mix. RESULTS: HNC reconstructive procedures reimburse lower than comparable breast procedures (p < 0.05). Nonprofit and research support for HNC is disproportionately low relative to disease burden. Patients hospitalized for HNC surgical procedures generated higher costs and lower charges than patients with BC (p < 0.05). CONCLUSION: Comparatively low procedure reimbursement, low nonprofit support, and high cost of care for patients with HNC relative to patients with BC may contribute to care disparities for patients with HNC.

Succinate dehydrogenase mutations in head and neck paragangliomas: A systematic review and meta-analysis of individual patients' data.

BACKGROUND: Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear. We sought to explore the demographics, clinical characteristics, treatment methods, and outcomes of SDH-mutated HNPs. METHODS: Databases were systematically searched. Pooled event ratio and relative 95% confidence intervals were calculated for dichotomous outcomes. Meta-regression was performed. Cochran's Q test and I2 test assessed heterogeneity. Funnel plot and Egger's regression test assessed publication bias. RESULTS: Forty-two studies with 8849 patients were included. Meta-regression revealed a significant correlation between multifocality and SDHD mutations (0.03 ± 0.006, p < 0.0001) and between distant metastases and SDHB mutations (0.06 ± 0.023, p = 0.008). There was no correlation between sex, age, tumor size, or familial occurrences and SDH-related mutations. CONCLUSION: Multifocality of HNPs correlates with the SDHD mutational subtype, and metastases correlate with the SDHB subtype. Knowledge of HNP phenotypes associated with SDH-related mutations has the potential to influence the management approach to such HNPs.

Multidisciplinary management of carotid body tumors: a single-institution case series of 22 patients.

OBJECTIVE: Carotid body tumors (CBTs) are rare, slow-growing neoplasms derived from the parasympathetic paraganglia of the carotid bodies. Although inherently vascular lesions, the role of preoperative embolization prior to resection remains controversial. In this report, the authors describe an institutional series of patients with CBT successfully treated via resection following preoperative embolization and compare the results in this series to previously reported outcomes in the treatment of CBT. METHODS: All CBTs resected between 2013 and 2019 at a single institution were retrospectively identified. All patients had undergone preoperative embolization performed by interventional neuroradiologists, and all had been operated on by a combined team of cerebrovascular neurosurgeons and otolaryngology-head and neck surgeons. The clinical, radiographic, endovascular, and perioperative data were collected. All procedural complications were recorded. RESULTS: Among 22 patients with CBT, 63.6% were female and the median age was 55.5 years at the time of surgery. The most common presenting symptoms included a palpable neck mass (59.1%) and voice changes (22.7%). The average tumor volume was 15.01 ± 14.41 cm3. Most of the CBTs were Shamblin group 2 (95.5%). Blood was predominantly supplied from branches of the ascending pharyngeal artery, with an average of 2 vascular pedicles (range 1-4). Fifty percent of the tumors were embolized with more than one material: polyvinyl alcohol, 95.5%; Onyx, 50.0%; and N-butyl cyanoacrylate glue, 9.1%. The average reduction in tumor blush following embolization was 83% (range 40%-95%). No embolization procedural complications occurred. All resections were performed within 30 hours of embolization. The average operative time was 173.9 minutes, average estimated blood loss was 151.8 ml, and median length of hospital stay was 4 days. The rate of permanent postoperative complications was 0%; 2 patients experienced transient hoarseness, and 1 patient had medical complications related to alcohol withdrawal. CONCLUSIONS: This series reveals that endovascular embolization of CBT is a safe and effective technique for tumor devascularization, making preoperative angiography and embolization an important consideration in the management of CBT. Moreover, the successful management of CBT at the authors' institution rests on a multidisciplinary approach whereby endovascular surgeons, neurosurgeons, and ear, nose, and throat-head and neck surgeons work together to optimally manage each patient with CBT.

Genomic signature of Fanconi anaemia DNA repair pathway deficiency in cancer.

Fanconi anaemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink repair resulting in chromosome breakage1-3. The FA repair pathway protects against endogenous and exogenous carcinogenic aldehydes4-7. Individuals with FA are hundreds to thousands fold more likely to develop head and neck (HNSCC), oesophageal and anogenital squamous cell carcinomas8 (SCCs). Molecular studies of SCCs from individuals with FA (FA SCCs) are limited, and it is unclear how FA SCCs relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or infection with human papillomavirus9 (HPV). Here, by sequencing genomes and exomes of FA SCCs, we demonstrate that the primary genomic signature of FA repair deficiency is the presence of high numbers of structural variants. Structural variants are enriched for small deletions, unbalanced translocations and fold-back inversions, and are often connected, thereby forming complex rearrangements. They arise in the context of TP53 loss, but not in the context of HPV infection, and lead to somatic copy-number alterations of HNSCC driver genes. We further show that FA pathway deficiency may lead to epithelial-to-mesenchymal transition and enhanced keratinocyte-intrinsic inflammatory signalling, which would contribute to the aggressive nature of FA SCCs. We propose that the genomic instability in sporadic HPV-negative HNSCC may arise as a result of the FA repair pathway being overwhelmed by DNA interstrand crosslink damage caused by alcohol and tobacco-derived aldehydes, making FA SCC a powerful model to study tumorigenesis resulting from DNA-crosslinking damage.

Paramaxillary CT-guided fine needle aspiration of head and neck lesions: technique, diagnostic yield, and safety profile.

Computed tomography (CT)-guided percutaneous biopsy of deep-seated head and neck lesions can be a less invasive and equally effective alternative to surgical techniques. There are multiple approaches for needle biopsy that target varying spaces within the head and neck while successfully avoiding critical anatomy. In the paramaxillary approach, the needle is advanced through the infrazygomatic buccal space, in between the maxilla and mandible. In this study, we examine the safety and diagnostic yield of FNA without core needle biopsy performed via the paramaxillary approach in 19 patients yielding 20 fine needle aspirates between 2014 and 2022. Of the fine needle aspirates, 85.0% (17/20) were diagnostic. Concordant histopathologic diagnosis was obtained in 100% (17/17) diagnostic fine needle aspirates. There were no postprocedural complications.

Identification of occult metastatic disease via lymphoscintigraphy-guided neck dissection in N0 oral squamous cell carcinoma.

BACKGROUND: The purpose of this study is to assess the efficacy of lymphoscintigraphy-guided neck dissection (LSG-ND) in the treatment of N0 oral squamous cell carcinoma. METHODS: A retrospective cohort study of patients with N0 oral squamous cell carcinoma (SCC) who had either LSG-ND or neck dissection (ND) at our institution between 2008 and 2020. RESULTS: Eighty-seven patients met criteria with N0 oral squamous cell carcinoma with no previous treatment or neck surgery (27 LSG-ND, 60 ND). Sentinel lymph nodes were identified on the contralateral side in 14.8% of patients with unilateral tumors in the LSG-ND group, with 22.2% of cases with unexpected lymphatic drainage outside ipsilateral levels I-III. No recurrences to date have occurred in the LSG-ND cohort, while 13.3% of patients with ND had regional recurrence (p = 0.04). CONCLUSIONS: LSG-ND provides a greater ability to identify occult metastatic disease with a significant reduction in regional recurrence in N0 oral SCC.

Microsurgical Head and Neck Reconstruction in Patients With Fanconi Anemia.

ABSTRACT: Patients with Fanconi anemia (FA) are at increased risk for head and neck cancers that often necessitate extensive reconstructions. Such patients have multiple comorbidities including anemia and thrombocytopenia frequently requiring bone marrow transplant, and they are at an increased risk of cancer recurrence and need for further extirpation. in the present study, charts from 3 patients with FA who underwent microvascular free tissue transfer by the senior author were retrospectively reviewed for pertinent pre- and peri-operative details in addition to functional and cosmetic outcomes. Two of these patients ultimately required metachronous free flap reconstructions for recurrence. All patients had acceptable functional and cosmetic outcomes following each instance of free flap reconstruction, thereby demonstrating the utility of microvas- cular free tissue transfer in patients with FA. The authors herein present each patient's clinical history in addition to a discussion of the current literature and an outline of our approach to these challenging cases.

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.

Establishing an Office-Based Framework for Resuming Otolaryngology Care in Academic Practice During the COVID-19 Pandemic.

OBJECTIVE: The COVID-19 health crisis abruptly disrupted the practice of otolaryngology. This article aims to define the changes needed to operate an academic otolaryngology practice safely and efficiently from within the epicenter of the pandemic. We define the areas of normal patient workflow that have been affected by COVID-19, and we offer mitigation strategies with attention paid to the specific needs of subspecialties. DATA SOURCES: The article includes data specific to the office practice metrics of the Weill Cornell Medicine Department of Otolaryngology-Head and Neck Surgery, as well as publically available data from New York Presbyterian Hospital system and the New York Times. REVIEW METHODS: Expert opinion. CONCLUSIONS: Through careful planning and execution, it is possible to reestablish safe otolaryngologic patient care during the COVID-19 pandemic. It will require a significant change from prior practice models for successful implementation. Additionally, telemedicine can be positively integrated into the treatment of otolaryngology diseases for new and established patients. IMPLICATIONS FOR PRACTICE: The information conveyed in this review can be used as a guide by large and small otolaryngology groups to identify aspects of the patient visit that are "at risk" due to COVID-19, and it suggests sensible responses that can be made without a significant disruption to normal practice. The methods used to identify vulnerabilities with the patient visit process can be applied to future unforeseen crises, such as a resurgence of COVID-19 or a novel pandemic.

Pain and Opioid Analgesic Use After Otorhinolaryngologic Surgery.

OBJECTIVE: To quantify pain and opioid use after otorhinolaryngologic surgery. To determine the effect of patient and surgical factors on primary outcomes. STUDY DESIGN: Prospective cohort. SETTING: Tertiary academic hospital. SUBJECTS AND METHODS: Patients undergoing elective otorhinolaryngologic surgery were prospectively enrolled. Patients completed demographic surveys and psychometric questionnaires assessing attitudes toward pain and baseline anxiety and depression before surgery. After surgery, patients documented peak pain levels (0-100 mm, visual analog scale) and daily prescription and nonprescription analgesic requirements over a 2-week period. Average daily and cumulative pain and opioid use were calculated and compared among patient cohorts stratified by procedure and preoperative factors. RESULTS: A total of 134 patients were enrolled. Total tonsillectomy was associated with significantly higher pain scores and opioid consumption, as compared to all other procedures. There was moderate correlation between average cumulative pain and opioid use. Older patients required significantly fewer doses of opioids. There was no effect of sex, marital status, or education level on postoperative pain or opioid use. Psychometric instrument scores and chronic pain or analgesic use were not associated with significant differences in pain or opioid requirements. Most patients were prescribed substantially more opioids than they actually required. CONCLUSION: Postoperative pain following elective otorhinolaryngologic surgery decreases dramatically within the first week and requires only few days of opioid analgesia, with the exception of tonsillectomy. Almost all patients required fewer than 15 doses of opioids.

Reconstruction of Full Thickness Scalp Defects in Extremely Elderly Patients Using Dermal Regeneration Templates.

The reconstruction of full thickness scalp defects following oncologic resection poses a unique challenge that is further magnified in "extremely elderly" patients, defined as those in at least their ninth decade of life, who are often unsuitable candidates for complex reconstruction. A "simpler" option is two-stage reconstruction: placement of Integra dermal regenerative template (Integra Life Science, Plainsboro, NJ) followed by a split thickness skin graft (STSG). This case series illustrates the success of this technique in the extremely elderly. A retrospective analysis of patients > 80 years at the time of surgery who underwent full thickness scalp reconstruction following tumor extirpation in a two-stage approach under the care of single surgeon from January 2010 to June 2019 was conducted. Variables reviewed were medical history, surgical treatment response, time to split thickness skin graft, follow up, and success of wound coverage. Fourteen patients, with a mean age of 87 years (range: 80 to 101, median: 87), met inclusion criteria. Split thickness skin grafts were placed after an average of 18 days. Twelve patients had successful two-stage reconstruction with 100% take. One patient developed a hematoma under a portion of the template that neither required reoperation nor delayed split thickness skin graft placement. A second suffered from insufficient vascularization of the template with delay to split thickness skin graft and incomplete wound closure. This two-stage approach is a successful primary reconstructive option for definitive management of full thickness scalp defects following oncologic resection in extremely elderly patients.

MicroRNA-based risk scoring system to identify early-stage oral squamous cell carcinoma patients at high-risk for cancer-specific mortality.

BACKGROUND: For early-stage oral squamous cell carcinoma (OSCC), there is no existing risk-stratification modality beyond conventional TNM staging system to identify patients at high risk for cancer-specific mortality. METHODS: A total of 568 early-stage OSCC patients who had surgery only and also with available 5-year clinical outcomes data were identified. Signature microRNAs (miRNAs) were discovered using deep sequencing analysis and validated by qRT-PCR. The final 5-plex prognostic marker panel was utilized to generate a cancer-specific mortality risk score using the multivariate Cox regression analyses. The prognostic markers were validated in the internal and external validation cohorts. RESULTS: The risk score from the 5-plex marker panel consisting of miRNAs-127-3p, 4736, 655-3p, TNM stage and histologic grading stratified patients into four risk categories. Compared to the low-risk group, the high-risk group had 23-fold increased mortality risk (hazard ratio 23, 95% confidence interval 13-42), with a median time-to-recurrence of 6 months and time-to-death of 11 months (vs >60 months for each among low-risk patient; p < .001). CONCLUSION: The miRNA-based 5-plex marker panel driven mortality risk score formula provides clinically practical and reliable measures to assess the prognosis of patients assigned to an early-stage OSCC.

Neither high-dose nor low-dose brachytherapy increases flap morbidity in salvage treatment of recurrent head and neck cancer.

PURPOSE: While brachytherapy is often used concurrently with flap reconstruction following surgical ablation for head and neck cancer, it remains unclear whether it increases morbidity in the particularly high risk subset of patients undergoing salvage treatment for recurrent head and neck cancer (RH&NC). MATERIAL AND METHODS: A retrospective chart review was undertaken that evaluated patients with RH&NC who underwent flap coverage after surgical re-resection and concomitant brachytherapy. The primary endpoint was flap viability, and the secondary endpoints were flap and recipient site complications. RESULTS: In the 23 subjects included in series, flap viability and skin graft take was 100%. Overall recipient site complication rate was 34.8%, high-dose radiation (HDR) group 50%, and low-dose radiation (LDR) group 29.4%. There was no statistically significant difference between these groups. CONCLUSIONS: In patients who undergo flap reconstruction and immediate postoperative radiotherapy following salvage procedures for RH&NC, flap coverage of defects in combination with brachytherapy remains a safe and effective means of providing stable soft tissue coverage.

Adoption of transoral robotic surgery compared with other surgical modalities for treatment of oropharyngeal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Transoral robotic surgery (TORS) has increased for treatment of oropharyngeal squamous cell carcinoma (OPSCC). To define the adoption of TORS, we analyzed patterns of surgical treatment for OPSCC in the US. METHODS: Cases of T1-T3 OPSCC treated with surgery between 2010 and 2013 from the National Cancer Database were queried. RESULTS: Of 3,071 patients who underwent primary surgical management for T1-T3 OPSCC, 846 (28%) underwent TORS. On multivariable analysis, low tumor stage (T2 vs. T1: OR 0.75, CI 0.37-0.51, P < 0.0001; T3 vs. T1: O.R. 0.33, CI 0.28-0.38, P < 0.0001), treatment at an academic cancer center (O.R. 2.23, C.I. 1.29-3.88, P = 0.004) and treatment at a high volume hospital (34-155 cases vs. 1-4 cases: O.R. 9.07, C.I. 3.19-25.79, P < 0.0001) were associated with increased TORS approach. Significant geographic variation was observed, with high adoption in the Middle Atlantic. Positive margin rates were lower when TORS was performed at a high volume versus low volume hospital (8.2% vs. 16.7% respectively, P = 0.001). CONCLUSIONS: Tumor and non-tumor factors are associated with TORS adoption. This analysis suggests uneven diffusion of this technology in the treatment of OPSCC. J. Surg. Oncol. 2016;114:405-411. © 2016 Wiley Periodicals, Inc.

Multiple endocrine neoplasia type 2 kindred with novel tandem RET mutations: Case report with an applied in silico mutational tolerance analysis.

BACKGROUND: The American Thyroid Association (ATA) has established guidelines for prophylactic thyroidectomy in multiple endocrine neoplasia type 2A (MEN2A) based on rearranged during transfection (RET) mutations. In silico analysis, which uses computer modeling to predict alterations in protein structure, is a new method for studying these mutations. METHODS: We describe a kindred with MEN2A, all sharing a well-documented RET mutation, p.C634Y, as well as a mutation of undetermined significance, p.I852M, which we analyzed via in silico analysis. RESULTS: The p.C634Y mutation resulted in severe predicted RET alterations, whereas the p.I852M resulted in only modest changes. Both mutations together resulted in only a small additional disruptive effect in protein structure beyond that which occurred with p.C634Y alone. CONCLUSION: Although in silico analysis may be helpful in quantitating changes in protein structure that occur in patients who have novel RET mutations (single or multiple), additional factors must account for the highly variable aggressiveness of the disease (C-cell hyperplasia/medullary thyroid carcinoma [MTC]) noted in our kindred. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1881-E1885, 2016.