Head and Neck Paragangliomas: Overview of Institutional Experience.

Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed between 1974 and 2023. The mean age of diagnosis was 48.8 years (range 10 to 82) with 69.0% female and 26.5% patients with multiple PGLs. Among 119 patients undergoing genetic testing, 70 (58.8%) patients had mutations, with SDHB (30) and SDHD (26) being the most common. The rates of metastasis and recurrence were higher among patients with SDHB mutations or SDHD mutations associated with multiple PGLs. Metabolic evaluation showed elevated plasma dopamine levels were the most common derangements in HNPGL. MRI and CT were the most common anatomic imaging modalities and DOTATATE was the most common functional scan used in this cohort. Most patients (81.5%) received surgery as the primary definitive treatment, while 22.5% patients received radiation treatment, mostly as an adjuvant therapy or for surgically challenging or inoperable cases. Systemic treatment was rarely used in our cohort. Our single-center experience highlights the need for referral for genetic testing and metabolic evaluation and for a team-based approach to improve the clinical outcomes of patients with HNPGLs.

Proposal for standardized ultrasound analysis of the salivary glands: Part 1 submandibular gland.

Objectives: The Salivary Gland Committee of the American Academy of Otolaryngology-Head and Neck Surgery seeks to standardize terminology and technique for ultrasonograpy used in the evaluation and treatment of salivary gland disorders. Methods: Development of expert opinion obtained through interaction with international practitioners representing multiple specialties. This committee work includes a comprehensive literature review with presentation of case examples to propose a standardized protocol for the language used in ultrasound salivary gland assessment. Results: A multiple segment proposal is initiated with this focus on the submandibular gland. We provide a concise rationale for recommended descriptive language highlighted by a more extensive supplement that includes an extensive literature review with additional case examples. Conclusion: Recommendations are provided to improve consistency both in performing and reporting submandibular gland ultrasound.

CIC-DUX4 Sarcoma Involving the Skull Base: A Rare Presentation and Review of the Literature.

Background CIC-DUX4 sarcoma is a rare, aggressive tumor that is difficult to diagnose. Although it is closely related to Ewing's sarcoma, each is a distinct pathologic entity and both have been previously reported in the skin, lymph nodes, and viscera. We report the first description of CIC-DUX4 involving the posterior cranial fossa and review the distinctive symptomatology, morphology, immunoprofile, and genetic signature that differentiate this rare tumor. Case Report A 32-year-old man presented with an enlarging right lateral neck mass, progressive hoarseness, and orofacial pain. Biopsy revealed a high-grade undifferentiated malignant neoplasm. Imaging demonstrated an 8-cm mass in the right neck extending to the skull base and abutting the carotid sheath, in addition to pulmonary nodules and pelvic lymphadenopathy. Despite initial response to chemotherapy, he experienced disease progression and underwent surgical resection, radical neck dissection, and brachytherapy. Definitive pathologic diagnosis was achieved with next-generation sequencing. Within weeks of treatment, he developed symptoms reflecting progression of disease involving the neck, posterior cranial fossa, and lung. Adjuvant chemotherapy was planned, but the patient succumbed to his disease prior to initiation of further therapy. Conclusion CIC-DUX4 sarcomas are uncommon and can progress rapidly. Diagnosis requires either fluorescence in situ hybridization or next-generation sequencing. Due to its rarity, there is no standard-of-care treatment for this tumor and further investigations are needed to understand disease behavior and develop targeted therapeutic modalities.

Carcinoma Ex Pleomorphic Adenomas: An Institutional Experience and Literature Review.

OBJECTIVES: To provide an institutional experience with cases diagnosed as carcinoma ex pleomorphic adenoma (CXPA), including the cytologic and histologic findings and clinical follow-up, followed by a comparison to the experience documented in the literature. METHODS: We identified cases of CXPA diagnosed at our institution from 2011 to 2021 and reviewed the cytologic and histologic diagnoses, as well as the treatment and clinical outcomes. Additionally, a literature review of the English literature was performed on CXPAs from 2011 to 2021. RESULTS: Forty-one cases of CXPA were identified, with the majority subclassified as adenocarcinoma, not otherwise specified. Five tumors underwent cytogenetic studies and five underwent molecular studies. To date, 36 patients are alive, 8 of whom experienced locoregional recurrence or distant metastasis. CONCLUSIONS: Our institutional experience was comparable to that reported in the literature. Further studies are required to inquire about the role of molecular profiles of CXPAs in clinical risk assessment.

Management of Chronic Sialadenitis due to Sjogren's Syndrome and Radioactive Iodine Therapy Using Sialendoscopy.

INTRODUCTION: Sialendoscopy is a minimally invasive technique for the management of salivary gland disease. This work characterizes its utility for treating chronic sialadenitis due to Sjogren's syndrome and radioactive iodine (RAI) therapy. METHODS: A single-center, retrospective review of patients undergoing sialendoscopy between March 2013 and May 2019 for the treatment of chronic sialadenitis due to Sjogren's or prior RAI therapy was performed. RESULTS: Thirty-four patients with Sjogren's and 25 patients who received RAI were identified, undergoing a total of 86 procedures. Median age at presentation was 53 years with mean follow-up time of 14.3 months. Seventy-two procedures were performed on the parotid gland, four on the submandibular gland, and ten on both glands. Corticosteroid injection and duct dilation were performed most commonly. Sixteen patients required repeat procedure. All patients were symptomatically improved at follow-up visit. DISCUSSION/CONCLUSION: These results support the idea that sialendoscopy offers symptomatic benefit for patients with chronic sialadenitis due to Sjogren's or RAI.

Post-operative Monitoring for Head and Neck Microvascular Reconstruction in the Era of Resident Duty Hour Restrictions: A Retrospective Cohort Study Comparing 2 Monitoring Protocols.

OBJECTIVES: To determine whether 2 different methods of post-operative head and neck free flap monitoring affect flap failure and complication rates. METHODS: A retrospective chart review of 803 free flaps performed for head and neck reconstruction by the same microvascular surgeon between July 2013 and July 2020 at 2 separate hospitals within the same healthcare system. Four-hundred ten free flaps (51%) were performed at Hospital A, a medical center where flap checks were performed at frequent, scheduled intervals by in-house resident physicians and nurses; 393 free flaps (49%) were performed at Hospital B, a medical center where flap checks were performed regularly by nursing staff with resident physician evaluation as needed. Total free flap failure, partial free flap failure, and complications (consisting of wound infection, fistula, and reoperation within 1 month) were assessed. RESULTS: There were no significant differences between Hospitals A and B when comparing rates of total free flap failure, partial free flap failure, complication, or re-operation (P = .27, P = .66, P = .65, P = .29, respectively). There were no significant differences in urgent re-operation rates for flap compromise secondary to thrombosis and hematoma (P = .54). CONCLUSIONS: In our series, free flap outcomes did not vary based on the degree of flap monitoring by resident physicians. This data supports the ability of a high-volume, well-trained, nursing-led flap monitoring program to detect flap compromise in an efficient fashion while limiting resident physician obligations in the age of resident duty hour restrictions.

Institutional analysis of intra- and post-operative tracheostomy management for risk reduction.

Objectives: Determine variability in intra- and post-operative management of tracheostomies (trachs) at our institution as existing literature suggests that trachs are a frequent trigger for airway-related emergencies. Catalyze the development of an institution-wide protocols for trach care. Methods: A 39-question online survey was sent to 55 providers who perform open and percutaneous trachs at three of the hospitals within our large, urban, academic medical center. These providers were identified by surveillance of the operating room schedules for 1 year. Results: The survey was completed by 40 of the 53 eligible providers (75.5%). Response rate by question varied. Respondents included members of all departments that perform trachs at our institution (Otorhinolaryngology, Trauma Surgery, Thoracic Surgery, General Surgery, Cardiovascular Surgery and Interventional Pulmonology).While most responses demonstrated uniformity in practice, notable variations included the following: 80% of percutaneous trach providers stated that morbid obesity was not a contraindication to performing a trach outside of the operating room (n = 20) while 58% of open trach providers stated that morbid obesity was a contraindication; only 35% of open trach providers perform a Bjork flap (n = 350). The survey also identified significant variability in practice with regards to timing of trach suture removal. Discussion: Lack of uniformity was identified in several practices related to intra- and post-operative tracheostomy care. Results did, however, trend toward consensus in many areas. The results are being used to establish a more consistent approach to tracheostomy management across our institution to ensure standardization of practice amidst the rapidly evolving practices of trach placement. Implications for practice: With ongoing evolution in the methods of trach placement and its management, the concepts put forth here will be a resource for health care providers at other institutions to consider intra-institutional analysis and establishment of practice standardization.

Retrospective Review of Surgical Site Infections after Endoscopic Endonasal Sellar and Parasellar Surgery: Multicenter Quality Data from the North American Skull Base Society.

Introduction Transnasal access to the anterior skull base provides a minimally invasive approach for sellar and parasellar masses compared with its open counterparts. The unique microbiome of the sinonasal mucosa provides distinct challenges not encountered with other cranial approaches. The use of antibiotics in these cases has not been standardized, and data remain scarce regarding infectious outcomes. Methods We conducted a multicenter retrospective analysis of shared quality data points for the endoscopic endonasal approach (EEA) for pituitary adenomas, along with other sellar and parasellar region masses that were included by participating institutions. Patient and operative characteristics, perioperative and postoperative antibiotic regimens and their durations, intraoperative and postoperative cerebrospinal fluid leak, and onset of postoperative meningitis and sinusitis were compared. Results Fifteen institutions participated and provided 6 consecutive months' worth of case data. Five hundred ninety-three cases were included in the study, of which 564 were pituitary adenomectomies. The incidences of postoperative meningitis and sinusitis were low (0.67 and 2.87% for all pathologies, respectively; 0.35% meningitis for pituitary adenomas) and did not correlate with any specific antibiotic regimen. Immunocompromised status posed an increased odds of meningitis in pituitary adenomectomies (28.6, 95% confidence interval [1.72-474.4]). Conclusions The results show no clear benefit to postoperative antimicrobial use in EEA, with further larger studies needed.

Contemporary Review of Submandibular Gland Sialolithiasis and Surgical Management Options.

One of the most common disorders of the salivary glands is obstructive sialolithiasis. Salivary gland obstruction is important to address, as it can significantly impact patient quality of life and can progress to extensive cellulitis and abscess formation if left untreated. For small and accessible stones, conservative therapies often produce satisfactory outcomes. Operative management should be considered when stones are inaccessible or larger in size, and options include sialendoscopy, laser lithotripsy, extracorporeal shockwave lithotripsy, transoral surgery, and submandibular gland adenectomy. Robotic approaches are also becoming increasingly used for submandibular stone management. The purpose of this review is to summarize the modern-day management of submandibular gland obstructive sialolithiasis with an emphasis on operative treatment modalities. A total of 77 articles were reviewed from PubMed and Embase databases, specifically looking at the pathophysiology, clinical presentation, diagnosis, and management of submandibular sialolithiasis.

A benchmark for oncologic outcomes and model for lethal recurrence risk after transoral robotic resection of HPV-related oropharyngeal cancers.

OBJECTIVES: Increasing use of transoral robotic surgery (TORS) is likely to impact outcomes for HPV+ oropharyngeal squamous cell carcinomas (OPSCCs). We aimed to describe oncologic outcomes for a large HPV+ OPSCC cohort after TORS and develop a risk prediction model for recurrence under this treatment paradigm. MATERIALS AND METHODS: 634 HPV+ OPSCC patients receiving TORS-based therapy at a single institution were reviewed retrospectively to describe survival across the entire cohort and for patients suffering recurrence. Risks for distant metastatic recurrence (DMR) and locoregional recurrence (LRR) were modeled using multivariate logistic regression analyses of case-control sub-cohorts. RESULTS: 5-year overall and recurrence-free survival were 91.2% and 86.1%, respectively. 5-year overall survival was 52.5% following DMR and 83.3% after isolated LRR (P = .01). In case-control analyses, positive surgical margins were associated with DMR (adjusted OR 5.8, CI 2.1-16.0, P = .001), but not isolated LRR, and increased DMR risk 4.2 fold in patients with early clinical stage disease. By contrast, LRR was associated with not receiving recommended adjuvant therapy (OR 13.4, CI 6.3-28.5, P < .001). CONCLUSIONS: This study sets a benchmark for oncologic outcomes from HPV+ OPSCC after TORS-based therapy. Under this treatment paradigm, margins are relevant for assessing lethal recurrence risk during clinical trial design and post-treatment surveillance.

A surgical needs assessment for airway rapid responses: A retrospective observational study.

BACKGROUND: Airway rapid response (ARR) teams can be compiled of anesthesiologists, intensivists, otolaryngologists, general and thoracic surgeons, respiratory therapists, and nurses. The optimal composition of an ARR team is unknown but considered to be resource intensive. We sought to determine the type of technical procedures performed during an ARR activation to inform team composition. METHODS: A large urban quaternary academic medical center retrospective review (2016-2019) of adult ARR patients was performed. Analysis included ARR demographics, patient characteristics, characteristics of preexisting tracheostomies, incidence of concomitant conditions, and procedures completed during an ARR event. RESULTS: A total of 345 ARR patients with a median age of 60 years (interquartile range, 47-69 years) and a median time to ARR conclusion of 28 minutes (interquartile range, 14-47 minutes) were included. About 41.7% of the ARR had a preexisting tracheostomy. Overall, there were 130 procedures completed that can be performed by a general surgeon in addition to the 122 difficult intubations. These procedures included recannulation of a tracheostomy, operative intervention, new emergent tracheostomy or cricothyroidotomy, thoracostomy tube placement, initiation of extracorporeal membrane oxygenation, and pericardiocentesis. CONCLUSION: Highly technical procedures are common during an ARR, including procedures related to tracheostomies. Surgeons possess a comprehensive skill set that is unique and comprehensive with respect to airway emergencies. This distinctive skill set creates an important role within the ARR team to perform these urgent technical procedures. LEVEL OF EVIDENCE: Epidemiologic/prognostic, level III.

Sex-based differences in outcomes among surgically treated patients with HPV-related oropharyngeal squamous cell carcinoma.

OBJECTIVES: Sex differences in surgically treated HPV-associated oropharyngeal squamous cell carcinoma are not defined due to the low number of affected women. We explored the oncologic outcomes of men and women with p16-positive oropharyngeal squamous cell carinoma treated with primary surgery. MATERIALS AND METHODS: Retrospective analysis of patients with HPV-related oropharyngeal cancer treated with surgery and pathology guided adjuvant therapy from 2007 to 2017. Primary end point was recurrence-free and overall survival. RESULTS: Of 468 men (86.7%) and 72 women (13.3%), women presented more often with clinical N0 nodal disease (25% vs 12.2%). There were no differences in adverse pathologic features or T stage, although women were more likely to present with N0 disease (16.7% vs 10%), less N2 disease (6.9% vs 17.7%, p = 0.03), and more stage I disease (88.9% vs 75%). As a result, women were more likely to undergo surgery alone (30.6% vs 14.1%) while men were more likely to require adjuvant radiation therapy (47.2% vs 36.1%). Four women (5.6%) and 30 men (6.4%, p = 0.8) died during follow-up. Multivariate analysis controlling for age, sex, treatment, and pathologic stage demonstrated no differences in overall survival between men and women. There were no differences in recurrence-free or overall survival between men and women at two and five years. CONCLUSIONS: Although women undergoing transoral robotic surgery for HPV+ oropharyngeal squamous cell carcinoma may have less advanced disease, upfront surgery with pathology-guided adjuvant therapy produces similar oncologic results in men and women while accounting for disease burden.

Sialendoscopy for sialodocholithiasis following submandibular gland excision: six variations on a theme.

Sialendoscopy is a minimally invasive technique that facilitates the diagnosis and treatment of sialolithiasis. This case series presents the novel use of sialendoscopy to treat sialodocholithiasis in six patients with a non-functional or surgically absent submandibular gland by a single surgeon at the University of Pennsylvania Health System between March 2013 and December 2019. The four female and two male patients had a median age of 56 years and mean follow-up of 16.2 months (range 1-44.5). All stones were successfully removed using sialendoscopy, and in 5 patients a combined approach was utilized. All patients remain asymptomatic at last clinical follow-up. We conclude that sialendoscopy is a viable, minimally invasive method for managing sialodocholithiasis in patients with prior submandibular gland excision or atretic gland. It is also useful as an assistive tool when approaching complex transcervical or transoral procedures in previously instrumented patients.

Definitive tumor directed therapy confers a survival advantage for metachronous oligometastatic HPV-associated oropharyngeal cancer following trans-oral robotic surgery.

OBJECTIVES: To assess the prognostic significance of oligometastatic versus polymetastatic disease in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), and to evaluate the impact of definitive tumor directed therapy on the survival outcomes for patients with oligometastatic disease when compared to systemic therapy. MATERIALS AND METHODS: This was a retrospective observational cohort study of patients with HPV-associated OPSCC who developed distant metachronous metastatic disease after undergoing initial primary surgical management from 2008 to 2017. We classified patients based on the extent of metastatic disease [Oligometastatic (≤5 metastases) and polymetastatic (>5 metastases)], and the initial treatment of metastatic disease [definitive tumor directed therapy (all metastases treated with surgery or radiotherapy) versus upfront systemic therapy]. RESULTS: Among 676 patients undergoing primary surgical management for HPV-associated OPSCC, 39 patients (5.8%) developed metastases after a median follow-up of 29.6 months (range 4.5-127.0). Of the 34 metastatic patients who met study criteria, 26 (76.5%) were oligometastatic and 8 (23.5%) were polymetastatic. Oligometastatic patients had improved median overall survival (OS) compared to polymetastatic patients (47.9 vs. 22.7 months, p = 0.036). For oligometastatic patients, definitive tumor directed therapy was associated with an improved median progression free survival (not reached vs 6.13 months, p = 0.001) and median OS (not reached vs 40.7 months, p = 0.004). CONCLUSION: In a cohort of patients surgically treated for HPV-associated OPSCC, metachronous metastatic disease was uncommon and, in most cases, considered oligometastatic. Oligometastasis portends a favorable prognosis and definitive tumor directed therapy may be associated with improved overall survival in these patients. Future multi-institutional efforts are warranted to further demonstrate the impact of definitive tumor directed therapy on disease outcomes.

TP53 Mutation and Extraneural Metastasis of Glioblastoma: Insights From an Institutional Experience and Comprehensive Literature Review.

Extraneural metastases of glioblastoma (GBM), although rare, are becoming an increasingly recognized occurrence. Currently, the biological mechanism underlying this rare occurrence is not understood. To explore the potential genomic drivers of extraneural metastasis in GBM, we present the molecular features of 4 extraneural metastatic GBMs, along with a comprehensive review and analysis of previously reported cases that had available molecular characterization. In addition to our 4 cases, 42 patients from 35 publications are reviewed. To compare the molecular profiles between GBM cases with extraneural metastasis and the general GBM population, genomic data from GBM samples in The Cancer Genome Atlas (TCGA) database were also analyzed. We found that 64.5% (20/31) of the cases with extraneural metastasis that were tested for TP53 changes had at least 1 TP53 pathogenic variant detected in either 1 or both primary and metastatic tumors. In contrast, TP53 mutation was significantly less frequent in the unselected GBM from TCGA (22.6%, 56/248) (P=0.000). In addition, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation was more common in unselected TCGA GBM cases (48.6%, 170/350) than in cases with extraneural metastasis (31.8%, 7/22), although not statistically significant. Although isocitrate dehydrogenase (IDH) mutation is a rare occurrence in high-grade astrocytomas, IDH-mutant grade 4 astrocytomas are at least as likely to metastasize as IDH wild-type GBMs; 3 metastatic cases definitively harbored an IDH1 (p.R132H) mutation in our analysis. Our findings not only provide potential biomarkers for earlier screening of extraneural metastasis, but could also suggest clues to understanding biological mechanisms underlying GBM metastasis, and for the development of therapeutic modalities.

Oncologic outcomes of transoral robotic surgery for HPV-negative oropharyngeal carcinomas.

BACKGROUND: Patients with human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) continue to experience disappointing outcomes following chemoradiotherapy (CRT) and appreciable morbidity following historical surgical approaches. We aimed to investigate the oncologic outcomes and perioperative morbidity of a transoral robotic surgery (TORS) approach to surgically resectable HPV-negative OPSCC. METHODS: Retrospective analysis HPV-negative OPSCC patients who underwent TORS, neck dissection and pathology-guided adjuvant therapy (2005-2017). RESULTS: Fifty-six patients (91.1% stage III/IV) were included. Three-year overall survival, locoregional control, and disease-free survival were 85.5%, 84.4%, and 73.6%, respectively (median follow-up 30.6 months, interquartile range 18.4-66.6). Eighteen (32.1%) patients underwent adjuvant radiotherapy and 20 (39.3%) underwent adjuvant CRT. Perioperative mortality occurred in one (1.8%) patient and hemorrhage occurred in two (3.6%) patients. Long-term gastrostomy and tracheostomy rates were 5.4% and 0.0%, respectively. CONCLUSION: The TORS approach for resectable HPV-negative OPSCC can achieve encouraging oncologic outcomes with infrequent morbidity.

Survival and toxicity in patients with human papilloma virus-associated oropharyngeal squamous cell cancer receiving trimodality therapy including transoral robotic surgery.

BACKGROUND: Patients with oropharyngeal cancer who undergo transoral robotic surgery (TORS) and have high-risk features generally receive adjuvant chemoradiotherapy or trimodality therapy (TMT). The notion that TMT leads to high toxicity is largely based on studies that included human papilloma virus (HPV)-negative cancers and/or nonrobotic surgery; we sought to describe outcomes in HPV-associated oropharyngeal squamous cell cancer (HPV + OPSCC) undergoing TORS-TMT. METHODS: In consecutive patients with HPV + OPSCC receiving TMT at an academic center from 2010 to 2017, survival was estimated using Kaplan-Meier methodology, and toxicities were ascertained via chart review. RESULTS: In our cohort of 178 patients, 5-year survival was 93.6%. Feeding tube rates were 25.8% at therapy completion and 0.7% at 1 year. Rates of grade ≥ 3 kidney injury, anemia, and neutropenia in cisplatin-treated patients were 2.7%, 3.4%, and 11.0%, respectively. CONCLUSIONS: Patients with HPV + OPSCC who underwent TORS-TMT had excellent survival and low rates of toxicity and feeding tube dependence. These outcomes compare favorably to historical cohorts treated with definitive chemoradiotherapy.

Oncologic and survival outcomes for resectable locally-advanced HPV-related oropharyngeal cancer treated with transoral robotic surgery.

OBJECTIVES: To determine whether up-front trans-oral robotic surgery (TORS) for clinically-staged locally-advanced human papillomavirus (HPV)-related oropharyngeal cancer is associated with oncologic and survival outcomes comparable to early-stage (cT1/T2) tumors. MATERIALS AND METHODS: Retrospective cohort study of 628 patients with HPV-related oropharyngeal cancer who underwent up-front TORS from 2007 to 2017. Patients were stratified into two cohorts based on early-stage (cT1/2) versus locally-advanced (cT3/4) tumor at presentation. RESULTS: We identified 589 patients who presented with early-stage tumors, and 39 patients with locally-advanced tumors. Of these, 73% of patients required adjuvant radiation, and 33% required adjuvant chemoradiation. There was no significant difference in the administration of adjuvant radiation or chemoradiation between the two cohorts. Patients in the locally-advanced disease cohort were significantly more likely to have Stage II/III disease by clinical and pathologic criteria by American Joint Committee on Cancer 8th edition criteria (p < 0.001). However, there was no significant difference in 5-year overall survival (OS) or recurrence-free survival (RFS) based on Kaplan-Meier survival estimates between the two cohorts (p = 0.75, 0.6, respectively), with estimated OS of 91% at 5 years, and estimated RFS of 86% at 5 years across the study population. CONCLUSIONS: Up-front TORS offers favorable survival outcomes for appropriately selected locally-advanced cases of HPV-related oropharyngeal cancer. Furthermore, up-front TORS is comparably effective in allowing avoidance of adjuvant therapy, particularly chemotherapy, in both cT1/T2 and locally-advanced HPV-positive oropharyngeal cancer. In the absence of clear technical contraindication to surgery, cT3/T4 classification should not be considered an absolute contraindication to surgery.