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.

Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers.

Activation of the PI3K and epidermal growth factor receptor (EGFR) pathway is able to drive oncogenesis in multiple human cancers, including head and neck squamous cell carcinoma. Targeted agents such as cetuximab and erlotinib are currently used in patients with head and neck squamous cell carcinoma, but, in this disease, the genomic alterations that cause pathway activation and determine response to pharmacologic inhibition remain ill-defined. Here, we present a detailed dissection of the EGFR/PI3K pathway, composed of sequencing of the core pathway components, and high-resolution genomic copy number assessment. Mutations were found in PIK3CA (6%), but no point mutations were observed in other pathway genes such as PTEN and EGFR. In contrast, we observed frequent copy number alterations of genes in the pathway, including PIK3CA, EGFR, protein tyrosine phosphatase receptor S (PTPRS), and RICTOR. In total, activating genetic pathway alterations were identified in 74% of head and neck tumors. Importantly, intragenic microdeletions of the EGFR phosphatase PTPRS were frequent (26%), identifying this gene as a target of 19p13 loss. PTPRS loss promoted EGFR/PI3K pathway activation, modulated resistance to EGFR inhibition, and strongly determined survival in lung cancer patients with activating EGFR mutations. These findings have important implications for our understanding of head and neck cancer tumorigenesis and for the use of targeted agents for this malignancy.

Safety of concurrent nasal and oropharyngeal surgery for obstructive sleep apnea.

OBJECTIVE: This study evaluated for increased complications or risk associated with concurrent nasal and oropharyngeal surgeries to treat patients with obstructive sleep apnea (OSA). STUDY DESIGN: Retrospective chart review. METHODS: We performed a retrospective chart review on consecutive patients between 2006 and 2011 who underwent either simultaneous nasal and pharyngeal surgery (group 1) or pharyngeal surgery alone (group 2) to treat OSA. We compared the length of hospitalization and the rate of complications in both groups. RESULTS: Group 1 consisted of 20 patients, all male, with ages ranging from 25 to 72 years (average, 35 years) and apnea-hypopnea index (AHI) from 2.6 to 119 (average, 52.2). Group 2 consisted of 20 patients, 1 female, with ages ranging from 23 to 71 years (average, 37 years) and AHI from 10 to 101 (average, 46.1). In group 1, 30% of patients were ambulatory compared to 25% of patients in group 2. In all cases, the nonambulatory patients were observed for only 1 night. The rate of complications in both groups was 10% (2 out of 20 in each group). Both complications in group 1 were post-tonsillectomy bleeds. In group 2, 1 patient had a post-tonsillectomy bleed and 1 patient was readmitted with dehydration due to poor pain control. There was no statistically significant difference in length of hospitalization or rate of complications in these 2 groups. CONCLUSION: Performing concurrent nasal and oropharyngeal surgery for OSA was safe when compared to oropharyngeal surgery alone in our cohort and, with careful selection criteria, can even be done in the ambulatory setting. Large, multi-institutional investigations are indicated.

The use of thyroid isthmusectomy for management of well differentiated thyroid carcinoma - A systematic review and meta-analysis.

OBJECTIVE: With the growing global incidence of thyroid carcinomas, there is an increasing need for distinct guidelines for isthmus-confined carcinomas. Here, we performed the first systematic review on the topic to date, aiming to provide understanding to isthmusectomy as surgical management for well-differentiated thyroid carcinoma of the isthmus. METHODS: We conducted a systematic review following the PRISMA guidelines, analyzing English-language studies from the past decade that report on thyroid isthmusectomy. Exclusion criteria included isthmusectomy performed alongside full thyroidectomy or partial thyroid lobectomy, lack of data on tumor characteristics or survival outcomes, and non-English publications where a translation was unavailable. Our review identified a total of 227 patients from seven studies. RESULTS: The average 5-year overall survival and disease-free survival rates for patients with isthmus-confined PTC who underwent isthmusectomy were 100 % and 93.1 %, respectively. Similar to that of total thyroidectomy. 3.1 % of patients required completion thyroidectomy. Furthermore, isthmusectomy resulted in fewer surgical complications than total thyroidectomy. CONCLUSIONS: The scarcity of studies providing detailed tumor characteristics and patient outcomes limits our ability to fully evaluate the safety and efficacy of isthmusectomy for isthmus-confined PTC. Additionally, the variable sample sizes and restricted geographic distribution of the included studies calls into questions the generalizability of their findings. Despite these limitations, the data suggest that isthmusectomy may be a viable surgical option for select patients with small, isthmus-confined PTC. In the absence of a randomized controlled trial on the noninferiority of isthmusectomy, significantly more publications are needed before strong conclusions can be drawn.

Transoral endoscopic vestibular approach Sistrunk procedure (TEVAS)-case report and scoping review.

Background: Thyroglossal duct cyst (TGDC) is the most common congenital neck mass among the pediatric population. Less than 10% of the cases occur in adults. The standard of care for TGDC is surgical treatment with the Sistrunk procedure via a traditional transverse cervicotomy. This technique involves the resection of the cyst with its tract and the central portion of the hyoid bone body to avoid recurrence. The transoral vestibular approach has gained popularity as an alternative approach to open neck surgery in order to eliminate the transcervical scar associated with these procedures. Methods: We describe a case of an endoscopic Sistrunk procedure performed by the transoral vestibular approach. A scoping review of the transoral endoscopic vestibular approach Sistrunk procedure (TEVAS) was performed. The PubMed, Medline, Cochrane, Lilacs, Scielo, Mary Ann Libert and Scopus databases were systematically searched by using a Medical Subject Heading (MeSH)-optimized search strategy. The selection of papers followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines after setting inclusion and exclusion criteria. Results: The case was successful and without complications. Five studies were included in the final analysis for this review. Conclusions: This novel approach to the Sistrunk procedure is an effective alternative way to treat TGDC in selected patients who are motivated to avoid a visible neck scar.

Scarless Neck Feminization: Chondrolaryngoplasty Through Endoscopic Transoral Vestibular Approach.

We present in this paper a novel approach to perform endoscopic chondrolaryngoplasty without any external visible scars. The technique involves utilizing the endoscopic transoral vestibular approach. We have modified the technique by using the placement of a suture immediately above the anterior commissure, which provides a marker for the inferior extent of cartilage resection. Laryngoscope, 133:1099-1102, 2023.

Airway injury from transoral endoscopic thyroidectomy vestibular approach.

BACKGROUND: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a novel technique that eliminates a cervical scar. This procedure carries unique risks, and data on outcomes are needed as more cases are performed. METHODS: We describe two cases of airway injury during the TOETVA. A description of the procedure and management of the injuries is outlined. RESULTS: In one case, a 3-mm injury in the thyrohyoid membrane was identified. The TOETVA was converted to an open approach due to significant inflammation in the setting of Graves' and the repair was performed while open. In the second case, a fracture occurred from the thyroid notch to Broyle's ligament without avulsion. A primary repair was endoscopically performed. CONCLUSIONS: Airway injury is a possible complication of both open thyroidectomy and TOETVA. For TOETVA, trauma is most likely to occur in the midline during Hegar dilation and trocar placement through the central incision.

Transoral endoscopic vestibular approach Sistrunk procedure: First reported case series.

BACKGROUND: Standard of care for management of thyroglossal duct cysts (TGDCs) is a Sistrunk procedure performed through a transcervical incision. We describe the first series of Sistrunk procedures performed through a transoral endoscopic vestibular approach, eliminating a visible external scar. METHODS: The transoral endoscopic vestibular approach to the Sistrunk (TEVAS) was performed in patients with TGDCs meeting inclusion criteria who desired a scarless approach. RESULTS: Six patients (five females and one male) underwent TEVAS, with a mean age of 38 years (range 16-56 years) and a mean TGDC size of 1.8 cm (range 1.1-2.4 cm). Mean operative time was approximately 5 h (range 2-8 h). There were no surgical complications or recurrences. CONCLUSIONS: For appropriately selected patients, the TEVAS is an alternative to open neck surgery that provides improved cosmesis while maintaining successful resection outcomes. More data on outcomes including complications and recurrences are needed as additional case information is collected.

Impingement of the Thyroid Cartilage on the Carotid Causing Clicking Larynx Syndrome and Stroke.

We present the case of a patient with a recent history of ischemic stroke who presented with clicking larynx syndrome, a condition in which clicking noises in the larynx can be provoked by movement of the head and neck. Diagnostic imaging revealed unusual development and posterior angulation of the superior horn of the thyroid cartilage that potentially was causing trauma to the left common carotid artery. We deduced that symptomatic impingement of the carotid artery by the thyroid cartilage was not only the cause of the patient's clicking larynx syndrome, but also suspected to be the cause of her prior strokes due to repetitive trauma resulting in thrombus. The patient was managed surgically with thyroplasty and transcervical resection of the left greater cornu of the thyroid cartilage with resolution of her symptoms. Anatomical displacement of the thyroid cartilage can manifest as clicking larynx syndrome as well as cause mechanical injury to the carotid artery, resulting in turbulent flow, possible thrombosis, and stroke. Laryngoscope, 132:1410-1413, 2022.

Times to Diagnosis, Staging, and Treatment of Head and Neck Cancer Before and During COVID-19.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has reduced the demand for, and supply of, head and neck cancer services. This study compares the times to diagnosis, staging, and treatment of head and neck cancers before and during the COVID-19 pandemic. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center in New York City (NYC). METHODS: The times to diagnosis, staging, and treatment of head and neck cancer for patients presenting to the clinics of 4 head and neck oncology surgeons with newly diagnosed head and neck cancers were compared between pre-COVID-19 and COVID-19 periods. RESULTS: Sixty-eight patients in the pre-COVID-19 period and 26 patients in the COVID-19 period presented with newly diagnosed head and neck cancer. Patients in the COVID-19 group had a significantly longer time to diagnosis than the pre-COVID-19 group after adjustment for age and cancer diagnosis (P = .02; hazard ratio [HR], 0.54; 95% CI, 0.32-0.92). Patients in the pre-COVID-19 and COVID-19 groups had no statistically significant differences in time to staging (P > .9; HR, 1.01; 95% CI, 0.58-1.74) or time to treatment (P = .12; HR, 1.55; 95% CI, 0.89-2.72). CONCLUSION: This study found that time to diagnosis for head and neck cancers was delayed during a COVID-19 period compared to a pre-COVID-19 period. However, there was no evidence of delays in time to staging and time to treatment during the COVID-19 period. Our results prompt further investigations into the factors contributing to diagnostic delays but provide reassurance that despite COVID-19, patients were receiving timely staging and treatment for head and neck cancers.

Immediate and partial neural dysfunction after thyroid and parathyroid surgery: Need for recognition, laryngeal exam, and early treatment.

BACKGROUND: Laryngeal dysfunction after thyroid and parathyroid surgery requires early recognition and a standardized approach for patients that present with voice, swallowing, and breathing issues. The Endocrine Committee of the American Head and Neck Society (AHNS) convened a panel to define the terms "immediate vocal fold paralysis" and "partial neural dysfunction" and to provide clinical consensus statements based on review of the literature, integrated with expert opinion of the group. METHODS: A multidisciplinary expert panel constructed the manuscript and recommendations for laryngeal dysfunction after thyroid and parathyroid surgery. A meta-analysis was performed using the literature and published guidelines. Consensus was achieved using polling and a modified Delphi approach. RESULTS: Twenty-two panelists achieved consensus on five statements regarding the role of early identification and standardization of evaluation for patients with "immediate vocal fold paralysis" and "partial neural dysfunction" after thyroid and parathyroid surgery. CONCLUSION: After endorsement by the AHNS Endocrine Section and Quality of Care Committee, it received final approval from the AHNS Council.

Value within otolaryngology: Assessment of the cost-utility analysis literature.

OBJECTIVE: To assess the characteristics and quality of cost utility analyses (CUA) related to otolaryngology within the CEA registry and to summarize their collective results. METHODS: All cost-utility analyses published between 1976 and 2011 contained in the Cost-Effectiveness Analysis Registry (CEA Registry) were evaluated. Topics that fall within the care of an otolaryngologist were included in the review regardless of the presence of an otolaryngologist author. Potential associations between various study characteristics and CEA registry quality scores were evaluated using the Pearson product moment correlation coefficient. RESULTS: Sixty-one of 2913 (2.1%) total CUA publications screened were related to otolaryngology. Eighteen of 61 (29.5%) publications included an otolaryngologist as an author. Fourteen studies agreed on the cost effectiveness of at least unilateral cochlear implantation and six of seven (85.7%) studies demonstrated the cost effectiveness of continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). Forty-six percent (28 of 61) of all manuscripts were published between 2008 and 2011. A more recent publication year was associated with a higher CEA registry quality score while the presence of an otolaryngologist author and journal impact factor had no significant correlation with the quality of the CUA. CONCLUSION: Based on current evidence in the CEA registry, unilateral cochlear implantation for hearing loss and CPAP for OSA are both cost-effective therapeutic interventions. Although CUAs in otolaryngology have increased in quantity and improved in quality in more recent years, there is a relative lack of CUAs in otolaryngology in comparison to other subspecialties.

Patterns of regional and distant metastasis in esthesioneuroblastoma.

OBJECTIVES/HYPOTHESIS: To define the incidence and risk factors of metastatic disease and the effectiveness of salvage therapy in esthesioneuroblastoma (ENB). STUDY DESIGN: Retrospective analysis of 57 patients presenting from 1979 through 2009. METHODS: Cumulative incidence of neck failure, distant failure, and survival were assessed using the Kaplan-Meier method. RESULTS: Overall survival for all patients was 85% at 5 years and 75% at 10 years. Overall survival was negatively impacted by intracranial tumor extension (P < 0.001), positive resection margins (P = 0.05), and neck metastases (P = 0.017). Neck lymph nodes were not routinely electively irradiated during this time period. Nodal metastases developed in 17% of patients at a median time of 60 months. Kadish stage was not associated with a risk of nodal metastasis (P = 0.78). After treatment for nodal recurrence, locoregional control was achieved in 78% of patients. Of patients developing nodal recurrence, more than half developed distant metastases. The cumulative incidence of distant metastasis was 39% at a median time of 40 months. Patients who presented with Kadish stage C or D had a significantly increased risk of distant failure (P < 0.001). In patients developing nodal (P = 0.017) or distant metastasis (P = 0.001), the probability of survival was significantly decreased. CONCLUSION: Regional and distant metastases in patients with esthesioneuroblastoma occur in a delayed fashion and negatively impact survival. Neck nodal recurrence may be a harbinger of distant metastases. At the Memorial Sloan Kettering Cancer Center, New York, New York, we now treat the majority of ENB patients with elective nodal irradiation. However, the chief obstacle to long-term cure is distant metastases. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1556-1561, 2016.

Cancers of the nose, sinus, and skull base.

Malignancies of the nose, sinus, and skull base are rare. The most common histologies are squamous cell carcinoma and adenocarcinoma. The most common primary sites are the nasal cavity and maxillary sinus. Management of these tumors is technically challenging because they often present in advanced stages with extensive disease invading important structures such as the orbit and the skull base. In the last few decades advances in surgical resection techniques, as well as improved strategies to deliver adjuvant radiation, have substantially improved the outcomes in patients with malignancies of the sinonasal tract and skull base.

Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation.

Aberrant Wnt signaling can drive cancer development. In many cancer types, the genetic basis of Wnt pathway activation remains incompletely understood. Here, we report recurrent somatic mutations of the Drosophila melanogaster tumor suppressor-related gene FAT1 in glioblastoma (20.5%), colorectal cancer (7.7%), and head and neck cancer (6.7%). FAT1 encodes a cadherin-like protein, which we found is able to potently suppress cancer cell growth in vitro and in vivo by binding ß-catenin and antagonizing its nuclear localization. Inactivation of FAT1 via mutation therefore promotes Wnt signaling and tumorigenesis and affects patient survival. Taken together, these data strongly point to FAT1 as a tumor suppressor gene driving loss of chromosome 4q35, a prevalent region of deletion in cancer. Loss of FAT1 function is a frequent event during oncogenesis. These findings address two outstanding issues in cancer biology: the basis of Wnt activation in non-colorectal tumors and the identity of a 4q35 tumor suppressor.

Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis.

Head and neck squamous cell carcinoma (HNSCC) remains a significant cause of morbidity and mortality. There has been a great interest in finding specific genomic changes which contribute to HNSCC tumorigenesis, especially within the chromosome 3p area, where high frequency of LOH (loss of heterozygosity) has been reported. However, tumor-suppressor genes that may account for the frequent LOH remain to be identified. Recently, one systematic study of genomic sequencing was performed on breast and colorectal cancers and 189 candidate cancer genes (CAN-genes) were reported. Among those CAN-genes, 13 genes are located on chromosome 3p. To investigate whether any of the 13 CAN-genes on chromosome 3p is relevant to HNSCC tumorigenesis, we examined their mutational profiles in eight HNSCC cell lines and 12 tumor-normal pairs of human HNSCC in this study. Three of the 13 CAN-genes, ALS2CL, EPHA3, and CMYA1, each was found to harbor a missense mutation (1/20, 5% for each of the three genes). The mutations appeared hemizygous and SNP array analyses showed that these missense mutations are accompanied by LOH on the remaining allele. In summary, our data offer further support that ALS2CL, EPHA3, and CMYA1 are bona-fide tumor-suppressor genes and contribute to the tumorigenesis of HNSCC. Our data suggest that multiple tumor-suppressor genes are likely to be involved in accounting for the high LOH on chromosome 3p in HNSCC.

Cystic fibrosis and endoscopic sinus surgery: Relationship between nasal polyposis and likelihood of revision endoscopic sinus surgery in patients with cystic fibrosis.

OBJECTIVES: To observe the extent of nasal polyposis endoscopically in a cystic fibrosis population before the first surgical intervention and to grade the extent using a modified Malm scale, to observe patients prospectively and record the need for revision endoscopic sinus surgery (ESS), and to compare this among the individual polyp grading groupings. DESIGN: Retrospective medical record review of data collected prospectively. SETTING: Tertiary care hospital. PATIENTS: Forty-nine consecutive patients with a clinical preoperative diagnosis of cystic fibrosis and sinusitis. MAIN OUTCOME MEASURES: Using a modified Malm scale, the extent of polyps was prospectively graded into 3 groups before the first surgical intervention. The number of patients needing revision ESS and the mean time to revision ESS were compared among the 3 groups. RESULTS: Forty-nine consecutive patients underwent ESS between 1992 and 2007. We used a 3-stage system for extent of polyposis: 16 patients were noted to have no polyps (grade A), 14 had mild polyposis (grade B), and 19 had extensive polyposis (grade C). During the study, 14 patients required revision surgery: 3 with mild polyps and 11 with extensive polyps. Mean time to revision surgery was 39.7 months for those with grade B and 23.8 months for those with grade C. In the overall statistical analysis, the rate of revision ESS was significantly different among the 3 groups (P < .001). In pairwise comparisons, there were significant differences between those with grades A and C (P < .001) and between those with grades B and C (P = .04) and a trend toward significance between those with grades A and B (P = .052). There were no complications from ESS. CONCLUSION: Preoperative grading of nasal polyposis in patients with cystic fibrosis can help assess the future likelihood of revision ESS.

Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex.

Recent findings implicate embryonic signaling centers in patterning the mammalian cerebral cortex. We used mouse in utero electroporation and mutant analysis to test whether cortical signaling sources interact to regulate one another. We identified interactions between the cortical hem, rich in Wingless-Int (WNT) proteins and bone morphogenetic proteins (BMPs), and an anterior telencephalic source of fibroblast growth factors (FGFs). Expanding the FGF8 domain suppressed Wnt2b, Wnt3a and Wnt5a expression in the hem. Next to the hem, the hippocampus was shrunken, consistent with its dependence for growth on a hem-derived WNT signal. Maintenance of hem WNT signaling and hippocampal development thus require a constraint on the FGF8 source, which is likely to be supplied by BMP activity. When endogenous BMP signaling is inhibited by noggin, robust Fgf8 expression appears ectopically in the cortical primordium. Abnormal signaling centers were further investigated in mice lacking the transcription factor EMX2, in which FGF8 activity is increased, WNT expression reduced, and the hippocampus defective. Suggesting that these defects are causally related, sequestering FGF8 in Emx2 homozygous mutants substantially recovered WNT expression in the hem and partially rescued hippocampal development. Because noggin can induce Fgf8 expression, we examined noggin and BMP signaling in the Emx2 mutant. As the telencephalic vesicle closed, Nog expression was expanded and BMP activity reduced, potentially leading to FGF8 upregulation. Our findings point to a cross-regulation of BMP, FGF, and WNT signaling in the early telencephalon, integrated by EMX2, and required for normal cortical development.