Surgical Management of the Neck in Oral Cavity Squamous Cell Carcinoma.

Oral cavity cancer remains a significant cause of morbidity and mortality globally, with a poor prognosis once the disease has metastasized to cervical lymph nodes. The anatomy of lymphatic drainage in the neck gives us a roadmap to follow when assessing for metastasis, although the predictive factors are still not well understood. The mainstay of treatment continues to be neck dissection. However, there is much debate on the management of the clinically negative neck. The necessity of elective neck dissection has been questioned in recent years, with other options such as sentinel lymph node biopsy gaining popularity. This review will explore the aspects of surgical management of the neck in oral cavity cancer and highlights the further research that needs to be done.

Parental leave and family building experiences among head and neck surgeons in the United States: Career impact and opportunities for improvement.

BACKGROUND: The availability of paid parental leave is an important factor for retention and wellness. The experiences of head and neck surgeons with parental leave have never been reported. METHODS: A survey was electronically distributed to head and neck subspecialty surgeons in the United States. Responses were collected and analyzed. RESULTS: Male surgeons had more children and took significantly less parental leave than women. Thirty percent of respondents reported that parental leave negatively impacted compensation, and 14% reported a delay in promotion due to leave, which impacted women more than men. The vast majority reported they are happy or neutral about covering those on leave. Most respondents utilized paid childcare, and approximately one quarter of respondents spending 11%-20% of their income on childcare. CONCLUSIONS: This study illuminates the current disparities regarding parental leave-taking within the subspecialty of head and neck surgery in the United States. Women surgeons are more likely to be impacted professionally and financially.

Carotid endarterectomy for the management of carotid stenosis occurring concurrently with head and neck cancer.

PURPOSE OF REVIEW: Currently, most patients with concurrent head and neck cancer (HNC) and carotid stenosis (CS) are treated disjointedly for their oncologic and vascular lesions. The purpose of this review is to evaluate literature exploring a novel approach to these cases that poses several advantages, in which carotid endarterectomy (CEA) is performed simultaneously with surgical resection of HNC. RECENT FINDINGS: Carotid stenosis is a common comorbidity of patients presenting with head and neck cancer as these pathologies have overlapping risk factors. Adjuvant oncologic therapy such as radiation therapy to the site of the lesion is known to increase development or progression of carotid stenosis. Performing simultaneous surgical management of CS and HNC decreases total procedures for the patient, provides a less challenging surgical field, and eliminates prioritization of treatment initiation for one pathology over the other. There has been limited reporting of simultaneous CEA with oncologic resection of HNC in the literature. However, of the 21 cases reviewed here, no perioperative strokes were reported with only one perioperative death from myocardial infarction. SUMMARY: Available literature supports that simultaneous CEA with oncologic resection of HNC is safe and may offer several advantages, although larger studies are required.

Surgical Management of Advanced Glottic Cancer.

In advanced glottic cancer, it is widely known that definitive chemoradiation can result in comparable survival outcomes to primary surgery. This deserves consideration given the immense effects total laryngectomy (TL) has on patients. It is important to consider that not all advanced glottic tumors should be treated in the same way, and surgical management remains a critical consideration for optimization of local control and survival outcomes. Advances in organ preservation surgery and the more developed understanding of the survival benefits of TL in extensive T4 disease further support the importance of surgery in the management of advanced glottic cancer.

Cautionary case for radial forearm free flap use in trisomy 21.

BACKGROUND: The radial forearm free flap (RFFF) is considered a workhorse for head and neck cancer reconstructive surgery due to its generally consistent anatomy, pliability, long pedicle, and accessible harvest location. METHODS: A 63-year-old male with trisomy 21 and recurrent midface basal cell carcinoma presented for surgical management. The patient underwent tumor resection including left infrastructure maxillectomy with ipsilateral rhinectomy. Preoperative Allen's test was normal; however, the planned osteocutaneous radial forearm free flap reconstruction was aborted intraoperatively due to aberrant vascular anatomy in the form of a diminutive radial artery branch. Reconstruction was instead performed with an anterolateral thigh free flap. RESULTS: The patient recovered well in the hospital and was subsequently discharged to his care facility. CONCLUSIONS: Radial artery anomalies may be present among trisomy 21 patients making reconstruction with a RFFF not feasible, and thus preoperative Doppler ultrasound to assess arterial anatomy is essential in this population.

The Tumor Immune Microenvironment Architecture Correlates with Risk of Recurrence in Head and Neck Squamous Cell Carcinoma.

Emerging evidence suggests that not only the frequency and composition of tumor-infiltrating leukocytes but also their spatial organization might be a major determinant of tumor progression and response to therapy. Therefore, mapping and analyzing the fine tumor immune architecture could potentially provide insights for predicting cancer prognosis. Here, we performed an explorative, prospective clinical study to assess whether structures within the tumor microenvironment can predict recurrence after salvage surgery in head and neck squamous cell carcinoma (HNSCC). The major immune subsets were measured using flow cytometry and co-detection by indexing (CODEX) multiparametric imaging. Flow cytometry underestimated the number of PMN-MDSCs and neutrophils in the tumor and overestimated the tumor-infiltrating lymphocyte frequency. An ad hoc computational framework was used to identify and analyze discrete cellular neighborhoods. A high frequency of tertiary lymphoid structures composed of CD31highCD38high plasma cells was associated with reduced recurrence after surgery in HNSCC. These data support the notion that the structural architecture of the tumor immune microenvironment plays an essential role in tumor progression and indicates that type 1 tertiary lymphoid structures and long-lived CD31highCD38high plasma cells are associated with good prognosis in HNSCC. SIGNIFICANCE: Imaging the spatial tumor immune microenvironment and evaluating the presence of type 1 tertiary lymphoid structures enables prediction of recurrence after surgery in patients with head and neck squamous cell carcinoma.

Redefining Perineural Invasion in Head and Neck Cutaneous Squamous Cell Carcinoma.

OBJECTIVE: Perineural invasion (PNI) negatively affects disease-specific survival in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC). We aim to analyze the prognostic implications of PNI-related features. STUDY DESIGN: Retrospective cohort study. SETTING: Academic tertiary care hospital. METHODS: Retrospective chart review was performed on 104 patients diagnosed with HNcSCC between January 2011 and October 2019 who underwent resection, parotidectomy, and neck dissection with more than 1 year of follow-up. PNI was classified as incidental (identified on histopathology alone) or clinical (present on radiography and/or physical exam). Primary outcome measures were overall survival and disease-free survival (DFS). Kaplan-Meier analysis, logistic regression, and Cox regression were performed. RESULTS: The overall 5-year DFS was 57.9%. Sixty-one patients had PNI. On histopathology, 28 lesions showed complete nerve encirclement, 10 involved >5 nerves, and 12 involved named nerves. Patients with facial weakness (P = .026) and positive margins (P = .0029) had a higher likelihood of histopathologic PNI, and positive margins retained significance on multivariable analysis (P = .0079). Worse DFS was seen in patients with PNI (P = .004), advanced tumor stage (P = .049), positive margins (P = .014), and >5 nerves involved (P = .0061). Furthermore, histopathologic PNI was a predictor of DFS (hazard ratio [HR], 3.07; 95% CI, 0.33-1.38; P = .0061) overall and in the clinical PNI cohort (HR, 3.43; 95% CI, 1.65-7.10; P = .00091). CONCLUSION: DFS was significantly worse in patients with PNI, facial nerve weakness, advanced T stage, positive margins, and multiple nerve involvement. Further characterization of PNI features may help improve prognostic predictions and identify patients who may benefit from more aggressive treatment.

Manifestations of Human Papillomavirus in the Head and Neck.

Human papillomavirus (HPV)-positive oropharyngeal cancers (OPC) are increasing due to infection with the virus. Most of the patients diagnosed with HPV-positive OPC are white men with numerous lifetime sexual partners who have smoked marijuana excessively. In working up the patient, it is important to obtain an extensive history and physical examination and obtain proper imaging. Once a full workup is done, it is crucial to engage a multidisciplinary team in treatment and continue following-up with the patient through posttreatment surveillance. Administering the HPV vaccine at a young age may help reduce the increasing rate of HPV-positive OPC in the future.

High-Risk Cutaneous Squamous Cell Cancer of the Head and Neck: Risk Factors for Recurrence and Impact of Adjuvant Treatment.

OBJECTIVES: The behavior of advanced cutaneous squamous cell carcinoma of the head and neck (HNcSCC) remains poorly understood, with highly variable risk factors and a paucity of data for adjuvant treatment. The objective of our study was to review the oncologic outcomes of patients with high-risk HNcSCC treated with surgery and to identify risk factors for treatment failure. STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective review of patients treated for HNcSCC with definitive surgery involving at least parotidectomy and neck dissection at a tertiary care academic center from 2011 to 2017 was conducted. The primary outcome was disease-free survival (DFS). RESULTS: One-hundred four patients with a median age of 68 years (range = 42-91 years) were reviewed. Twenty-one patients were treated with surgery alone, 45 patients underwent adjuvant radiotherapy (RT), and 38 patients underwent adjuvant chemoradiotherapy (CRT). The 2-year DFS for patients treated with surgery, surgery + RT, and surgery + CRT were 71%, 65%, and 58%, respectively, with no significant difference between the groups (P = .70). On multivariate analyses, tumor size (P = .006) and perineural invasion (PNI, P = .04) independently predicted recurrence. The addition of chemotherapy did not appear to improve DFS, neither for those patients with extranodal extension and/or positive margins (P = .93) nor for the entire cohort (P = .43). CONCLUSIONS: Advanced HNcSCC has a high recurrence rate despite adjuvant treatment. Tumor size >2 cm was a strong independent risk factor for recurrence. Out of the traditional mucosal HNcSCC risk factors, PNI was most strongly associated with worse DFS. There was no observed survival benefit to the addition of chemotherapy. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E136-E143, 2021.

Molecular and Cellular Mechanisms of Perineural Invasion in Oral Squamous Cell Carcinoma: Potential Targets for Therapeutic Intervention.

The most common oral cavity cancer is squamous cell carcinoma (SCC), of which perineural invasion (PNI) is a significant prognostic factor associated with decreased survival and an increased rate of locoregional recurrence. In the classical theory of PNI, cancer was believed to invade nerves directly through the path of least resistance in the perineural space; however, more recent evidence suggests that PNI requires reciprocal signaling interactions between tumor cells and nerve components, particularly Schwann cells. Specifically, head and neck SCC can express neurotrophins and neurotrophin receptors that may contribute to cancer migration towards nerves, PNI, and neuritogenesis towards cancer. Through reciprocal signaling, recent studies also suggest that Schwann cells may play an important role in promoting PNI by migrating toward cancer cells, intercalating, and dispersing cancer, and facilitating cancer migration toward nerves. The interactions of neurotrophins with their high affinity receptors is a new area of interest in the development of pharmaceutical therapies for many types of cancer. In this comprehensive review, we discuss diagnosis and treatment of oral cavity SCC, how PNI affects locoregional recurrence and survival, and the impact of adjuvant therapies on tumors with PNI. We also describe the molecular and cellular mechanisms associated with PNI, including the expression of neurotrophins and their receptors, and highlight potential targets for therapeutic intervention for PNI in oral SCC.

Changes in head and neck oncologic practice during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has raised controversies regarding safe and effective care of patients with head and neck cancer. It is unknown how much the pandemic has changed surgeon practice. METHODS: A questionnaire was distributed to head and neck surgeons assessing opinions related to treatment and concerns for the safety of patients, self, family, and staff. RESULTS: A total of 88 head and neck surgeons responded during the study period. Surgeons continued to recommend primary surgical treatment for oral cavity cancers. Respondents were more likely to consider nonsurgical therapy for patients with early glottic cancers and HPV-mediated oropharynx cancer. Surgeons were least likely to be concerned for their own health and safety and had the greatest concern for their resident trainees. CONCLUSIONS: This study highlights differences in the willingness of head and neck surgeons to delay surgery or alter plans during times when hospital resources are scarce and risk is high.

False-positive reverse transcriptase polymerase chain reaction screening for SARS-CoV-2 in the setting of urgent head and neck surgery and otolaryngologic emergencies during the pandemic: Clinical implications.

BACKGROUND: No reports describe falsepositive reverse transcriptase polymerase chain reaction (RT-PCR) for novel coronavirus in preoperative screening. METHODS: Preoperative patients had one or two nasopharyngeal swabs, depending on low or high risk of viral transmission. Positive tests were repeated. RESULTS: Forty-three of 52 patients required two or more preoperative tests. Four (9.3%) had discrepant results (positive/negative). One of these left the coronavirus disease (COVID) unit against medical advice despite an orbital abscess, with unknown true disease status. The remaining 3 of 42 (7.1%) had negative repeat RT-PCR. Although ultimately considered falsepositives, one was sent to a COVID unit postoperatively and two had urgent surgery delayed. Assuming negative repeat RT-PCR, clear chest imaging, and lack of subsequent symptoms represent the "gold standard," RT-PCR specificity was 0.97. CONCLUSIONS: If false positives are suspected, we recommend computed tomography (CT) of the chest and repeat RT-PCR. Validated serum immunoglobulin testing may ultimately prove useful.

Update on anterior skull base reconstruction.

PURPOSE OF REVIEW: Anterior skull base reconstruction has rapidly evolved over the past few years as endoscopic approaches to resect tumors in this region have become more established. The present review evaluates the robust amount of new literature on this topic over the past year with particular attention to minimally invasive methods for reconstruction. RECENT FINDINGS: Although vascularized local flaps remain the mainstay reconstructive choice when available for the anterior skull base, innovative techniques for all types of reconstruction, ranging from free grafts to free flaps continue to emerge. SUMMARY: Because of the unique challenges and wide variety of options available to repair the anterior skull base with the goal to prevent or treat cerebrospinal fluid leaks, surgical expertise and experience in this field is of utmost importance.

Controversies in free tissue transfer for head and neck cancer: A review of the literature.

BACKGROUND: Microvascular free tissue transfer provides superior functional outcomes when reconstructing head and neck cancer defects. Careful patient selection and surgical planning is necessary to ensure success, as many preoperative, intraoperative, and postoperative patient and technical factors may affect outcome. AIMS: To provide a concise, yet thorough, review of the current literature regarding free flap patient selection and management for the patient with head and neck. MATERIALS AND METHODS: PubMed and Cochrane databases were queried for publications pertaining to free tissue transfer management and outcomes. RESULTS: Malnutrition and tobacco use are modifiable patient factors that negatively impact surgical outcomes. The use of postoperative antiplatelet medications and perioperative antibiotics for greater than 24 hours have not been shown to improve outcomes, although the use of clindamycin alone has been shown to have a higher risk of flap failure. Liberal blood transfusion should be avoided due to higher risk of wound infection and medical complications. DISCUSSION: There is a wide range of beliefs regarding proper management of patients undergoing free tissue transfer. While there is some data to support these practices, much of the data is conflicting and common practices are often continued out of habit or dogma. CONCLUSION: Free flap reconstruction remains a highly successful surgery overall despite as many different approaches to patient care as there are free flap surgeons. Close patient monitoring remains a cornerstone of surgical success.

Abnormal Microvasculature in Laryngectomy Mucosal Margins may be Associated with Increased Risk of Fistula.

Pharyngocutaneous fistula after laryngectomy is common and significantly increases the morbidity of the procedure. Intraoperative, objective variables that can reliably predict fistula formation would be useful to surgeons deciding how to reconstruct the laryngectomy defect. Retrospective chart review of 50 radiated patients and 10 non-radiated patients who underwent total laryngectomy at a single tertiary care institution. Patients with pharyngocutaneous fistula were selected to ensure a representative sample were available for comparison. All patients had pathology slides available for re-review by a single, blinded pathologist. Margins of both radiated (n = 50) and non-radiated (n = 10) larynges were examined for 7 histologic features, and odds ratios were calculated to assess whether these features were associated with fistula. When evaluating all 60 patients, both telangiectatic capillaries and hyalinized arterioles were associated with fistula (OR 3.72 and 9.21, respectively). Collinearity between the variables was evaluated; findings indicated a high likelihood of having hyalinized arterioles if telangiectatic capillaries were also present (OR 31.67 [3.13, 320.06]). Microvascular changes in radiated tissue have previously been described in other anatomic subsites, but the larynx and pharynx have not been specifically evaluated. Laryngectomy mucosal margins appear to display similar changes, and evidence of this damage may be associated with fistula formation. These features could potentially guide the surgeon to alter the reconstructive technique.

Disparities in adherence to head and neck cancer follow-up guidelines.

OBJECTIVES: In this study, we aim to determine the frequency of adherence to National Comprehensive Cancer Network follow-up guidelines in a population of head and neck cancer patients who received curative treatment. We will also assess the impact of race, ethnicity, socioeconomic status, and treatment setting on utilization of follow-up care. METHODS: This study included patients with biopsy-proven, nonmetastatic oropharyngeal or laryngeal cancer treated with radiotherapy between January 1, 2014, and June 30, 2016, at a safety-net hospital or adjacent private academic hospital. Components of follow-up care analyzed included an appointment with a surgeon or radiation oncologist within 3 months and posttreatment imaging of the primary site within 6 months. Univariable and multivariable analyses were conducted using a logistic regression model to estimate odds ratios and corresponding 95% confidence intervals. RESULTS: Two hundred and thirty-four patients were included in this study. Of those, 88.8% received posttreatment imaging of the primary site within 6 months; 88.5% attended a follow-up appointment with a radiation oncologist within 3 months; and 71.1% of patients attended a follow-up appointment with a surgeon within 3 months. On multivariable analysis, private academic hospital treatment versus safety-net hospital treatment was associated with increased utilization of both surgical and radiation oncology follow-up. Non-Hispanic black (NHB) patients, Hispanic patients, and those with a low socioeconomic status were also less likely to receive follow-up. CONCLUSION: Safety-net hospital treatment, socioeconomic status, Hispanic ethnicity, and NHB race were associated with decreased follow-up service utilization. Quality improvement initiatives are needed to reduce these disparities. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:2303-2308, 2019.

Meta-analysis comparing outcomes of different transoral surgical modalities in management of oropharyngeal carcinoma.

BACKGROUND: Optimal transoral surgical modality for oropharyneal carcinoma is currently unclear. Transoral laser surgery (TLS), transoral robotic surgery (TORS), and conventional direct transoral (DT) oropharyngectomy are the main current transoral surgical modalities for oropharyngeal carcinoma. METHODS: MEDLINE was systematically searched through PubMed. Reference lists were reviewed. Random-effects models were used to combine studies within each group. Tests for heterogeneity were used to explore difference in effect size between groups in subgroup analysis. RESULTS: Nine studies (404 patients) in TORS arm, five studies (498 patients) in TLS arm, and three studies (335 patients) in DT arm were included. Early T classification (T1-T2) for TORS and DT were higher compared to TLS group (P < .001). There was no significant difference between groups in the rate of invaded margin, post-operative oropharyngeal bleeding, temporary tracheotomy, and gastrostomy dependence. CONCLUSION: The available data do not yet provide clear evidence of superiority of any one modality.

Lymphoepithelial carcinoma of the major salivary glands: Predictors of survival in a non-endemic region.

INTRODUCTION: Lymphoepithelial carcinoma (LEC) of the salivary glands is extremely rare worldwide, with studies limited to small case reports and case series from endemic areas (Southern China, Arctic Inuits) and strong association to Epstein Barr Virus (EBV). Studies on non-endemic regions are even more limited given the reality of only sporadic cases in these areas. Using the National Cancer Database (NCDB), we present the largest study on salivary LEC from a non-endemic region, the United States. METHODS: A retrospective review of the NCDB from 1998-2012 for LEC of the major salivary glands was performed. Demographic and clinical variables were extracted for analysis. Multivariate COX regression was used to assess predictors of survival. RESULTS: Two hundred and thirty-eight cases were identified (0.66% of all salivary cancers). Median age at diagnosis was 62 with peak incidence in ages 50-70. Most patients were Caucasian (81.2%), without gender preference. Regional metastasis was common (45.1%) and did not significantly impact survival. Distant metastasis was rare (2%). Overall survival (OS) at 5- and 10 years was 77% and 56%. Surgery and radiotherapy significantly showed better survival outcomes than surgery alone (p<0.001). Age >62, advanced stage, and dual modality therapy were significant predictors of survival in multivariate analysis. CONCLUSION: Lymphoepithelial carcinoma in the US mostly affects an older, Caucasian demographic. Regional metastasis is common and survival is fair at 5- and 10 years. Surgery and radiation are recommended for early and advanced disease stages. Age, stage, and therapy are significant predictors of survival outcomes.

IL-1 Receptor Antagonist Inhibits Early Granulation Formation.

PURPOSE: Using a functional model of airway granulation tissue in laryngotracheal stenosis, we investigated changes in histopathology and inflammatory markers within granulation tissue in response to an interleukin-1 receptor antagonist (IL-1Ra). This study allows us to further delineate the immune response to wound healing and potentially identify treatment markers. METHODS: Laryngotracheal complexes (LTCs) of donor mice underwent direct airway injury. The LTCs were transplanted into subcutaneous tissue of recipient mice in 2 groups: IL-1Ra treated and untreated. The IL-1Ra-treated arm received daily intraperitoneal injections of IL-1Ra for 3 weeks. The LTCs were then harvested. Granulation formation was measured. The mRNA expression of transforming growth factor (TGF) beta and IL-1 was quantified using real-time reverse transcript polymerase chain reaction. RESULTS: There were statistically significant differences in lamina propria thickness. There were no statistically significant changes in mRNA expression of TGF-ß and IL-1ß between the treated and untreated specimens. CONCLUSIONS: Using a previously described murine model, we delineate inflammatory markers that can be targeted for potential therapy. While the levels of inflammatory markers do not change significantly, the lamina propria thickness shows that the effects of IL-1 have been inhibited. The early use of the IL-1Ra will inhibit the efficacy of IL-1 in the inflammatory cascade and can prevent early granulation formation.