Stephanie Flukes

Background: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with poor clinical outcomes. microRNA-7-5p (miR-7-5p) has been described as both a tumour suppressor and an oncomiR depending on the tissue context, but its role in HNSCC remains unclear. This study aimed to clarify the clinical significance and biological function of miR-7-5p in HNSCC by integrating data from multiple sources. Methods: A systematic review of the literature was conducted to identify studies analysing miRNA expression in human head and neck tissues. A meta-analysis of individual patient data from Gene Expression Omnibus (GEO), ArrayExpress, and The Cancer Genome Atlas (TCGA) was performed to assess miR-7-5p expression in tumours and normal tissues, and its associations with clinical parameters and prognostic outcomes. Bioinformatics analyses were used to predict miR-7-5p target genes, classify hub genes, and perform gene ontology enrichment analysis. MicroRNA in situ hybridisation (miRNA ISH) and real-time quantitative PCR (RT-qPCR) were conducted on tissue samples, HNSCC cell lines, and an in vitro model of oral oncogenesis to validate miR-7-5p expression patterns. Results: miR-7-5p was significantly upregulated in tumours compared to normal tissues and associated with larger tumour size, HPV-negative status, poor disease-specific survival, and shorter progression-free intervals. Bioinformatics analysis highlighted miR-7-5p target genes enriched in pathways related to cell growth, survival, and tumourigenesis. Despite evidence supporting the anti-cancer role of exogenous miR-7-5p in preclinical models, the observed endogenous upregulation in tumours suggests that miR-7-5p expression may represent a compensatory or stress-responsive mechanism during tumourigenesis, rather than acting as a primary oncogenic driver. Conclusions: This study provides new insights into the complex role of miR-7-5p in HNSCC, supporting its potential as both a biomarker and a therapeutic target. Understanding the context-specific functions of miR-7-5p is essential for its development as an RNA-based therapeutic in HNSCC.

Background: Endoscopic endonasal skull base surgery has become a viable alternative to open procedures for the surgical treatment of benign and malignant lesions in the sinonasal and skull base regions. As in sinus surgery, skull base surgery may cause crusting and posterior rhinorrhea, particularly when a nasoseptal flap is required for skull base reconstruction. Post-operative radiological sinonasal findings have been reported previously with no clear correlation with intraoperative decision-making. As in open surgery, endoscopic surgery is not standardized and there is variability in the intervention to assist with exposure and skull base repair. These modifications, including middle turbinate resection, nasoseptal flap, fat graft, and maxillary antrostomy have the potential for nasal morbidity. The aim of this study was to evaluate whether specific interventions during surgery or specific patient and tumor characteristics harbor a more significant risk of causing nasal morbidity post-operatively, as demonstrated by post-operative imaging. Methods: A retrospective analysis of all patients who underwent endoscopic endonasal skull base surgery for pituitary lesions at two major referral centers was performed. Data on demographic, clinical, and pathological features were collected, and pre- and post-operative imaging studies (computed tomography (CT) and magnetic resonance imaging (MRI)) were reviewed and scored according to the Lund–Mackay (LM) scoring system. Results: The study included 183 patients. Radiographic evidence of sinusitis was observed in 30 patients (LM score > 4) in post-operative imaging studies. Patients who underwent middle turbinectomy or nasoseptal flap were found to have significantly higher LM scores on follow-up imaging. A nasoseptal flap was found to be associated with an average increase in LM score of 1.67 points and middle turbinectomy with an average increase of 2.21 points. There was no correlation between tumor size and findings that were compatible with sinusitis on post-operative imaging. Conclusions: The findings of the present study suggest that endoscopic endonasal skull base surgery is associated with radiological evidence of sinusitis. Nasoseptal flap reconstruction and middle turbinectomy were strongly associated with radiographic sinusitis and should be judiciously performed during surgery. A clinical correlation is needed for further recommendations.

Introduction: Elderly patients (≥80 years of age) with head and neck cancer (HNC) can prove a management challenge due to concerns regarding their suitability for surgery. This study aims to describe the characteristics and outcomes of elderly patients undergoing HNC surgery.Methods: A retrospective review of elderly patients undergoing HNC surgery was conducted. Demographics, comorbidities, tumor characteristics, surgical procedure type, postoperative complications, and disposition were reviewed. Overall survival (OS) in the elderly cohort was compared against younger patients (80 years (71% male; mean age 84.8, range 80.0–98.8 years). The overall complication rate was 43%. When compared with younger patients (n = 509), elderly patients had reduced OS (risk ratio: 2.0, 95% CI: 1.3–3.2), higher 90‐day mortality (8.1% vs. 2.3%, p = .005), and lower 5‐year survival (43.5% vs. 64.1%, p < .001). However, survival was comparable to age‐specific life expectancy. There was no difference in OS, 90‐day mortality, and 5‐year survival when comparing >85 (n = 33) and 80–85 (n = 53) age groups.Conclusions: Chronological age alone should not negatively influence decision‐making in HNC surgery the elderly. With careful preoperative selection and optimization, surgery can be performed at acceptable risk with good outcomes in elderly patients.Level of evidence: IV

The authors describe a difficult case of symptomatic pedicle ossification in a fibular free flap reconstruction of the head and neck region.

Background: Patients receiving primary (chemo)radiotherapy for laryngeal or hypopharyngeal cancer risk developing severe laryngeal dysfunction and becoming tracheostomy dependent, detracting from the benefits of organ preservation. We aim to describe the airway outcomes for this cohort and identify risk factors for developing tracheostomy dependence.Methods: Patients with laryngeal or hypopharyngeal cancer who were recommended for and underwent primary (chemo)radiotherapy over a 6‐year period were identified from a tertiary hospital Head and Neck cancer database. Patient, tumor, and treatment details were collected and analyzed.Results: Of 166 patients, 18.7% (N = 31) required tracheostomy insertion. Advanced tumor classification was the only significant predictor (p < 0.00001). Successful decannulation was observed in 12.9% (N = 4). Decannulation was observably less successful with advanced tumors, bilateral vocal cord immobility, tracheostomies inserted under emergency conditions.Conclusion: We quantified tracheostomy insertion rates and dependence in patients undergoing “organ‐preserving” (chemo)radiotherapy, to assist in the pre‐treatment counseling of patients opting for this approach.

Background: There is no registry data on morbidity and mortality of high‐risk cutaneous squamous cell carcinoma (cSCC) in Australia.Aim: To examine the clinicopathological features, mortality and morbidity in high‐risk cSCC patients in Western Australia (WA).Methods: A retrospective cohort study was conducted through hospital record review on cSCC patients discussed at multidisciplinary meetings at the two largest WA hospitals between March 2015 and December 2016.Results: Of 141 patients, 129 were evaluable, with median follow up of 43.9 (range 3.0–53.2) months. Patients were predominantly older males (84%) with significant comorbidities (Charlson Comorbidity Index (CCI) ≥5; 76%) and history of previous nonmelanoma skin cancer (57%) with advanced disease (57% stage IV without distant metastasis; American Joint Committee on Cancer, 7th edition). Pathological high‐risk features were common including nodal extracapsular extension (47%) and cranial nerve involvement (16%). Clinical morbidity was significant with a median of 2 (range 0–13) excisions and 2 (range 0–21) cSCC‐related hospitalisations for any cSCC event following the index case discussion. Recurrences of the primary index lesion occurred in 60% of patients and 20% had ≥2 recurrences. Median overall survival for patients with nonmetastatic disease was 39.8 (range 25.9–53.7) months and 16.1 (range 0.2–32.0) months for metastatic disease. CCI ≥5, advanced nodal stage and ≥2 recurrences were significantly associated with mortality on multivariable analyses (P < 0.05). Nodal extracapsular extension and any recurrences were identified as significant risk factors for disease‐specific mortality on multivariable analyses (P < 0.05).Conclusion: High‐risk cSCC patients have significant health needs represented by high‐baseline comorbidities, multiplicity of cSCC events and the number of healthcare‐associated interventions. There is an unmet need for robust cancer data collection.

Introduction and importance: This is the first case of delayed tracheal perforation post total thyroidectomy in the context of previous radiotherapy to the neck. Such a presentation can be easily misdiagnosed and managed as a seroma at significant risk to the patient, as the latter had no precipitating factors and cardiorespiratory compromise. There are nineteen previously described cases of delayed tracheal injury post thyroidectomy of variable severity and variable intervention. Case presentation: A 51-year-old man presented with non-tender anterior neck surgical emphysema initially diagnosed on bedside ultrasound and plain X-ray, 22 days following total thyroidectomy and central neck dissection. His background was significant for childhood acute lymphoblastic leukaemia requiring chemotherapy and cranio-spinal radiotherapy. He underwent total thyroidectomy, for multiple bilateral thyroid nodules found on cranio-spinal MRI surveillance concerning for follicular neoplasm. There were significant amount of adhesions tethering the thyroid secondary to prior radiotherapy but no tracheal injury intra-operatively. Clinical discussion: At presentation, no source of air leak was identified on Computer Tomography. He failed conservative management. During surgical exploration, a 2 mm tracheal perforation at the right cricothyroid joint was closed with the right sternothyroid muscle due to the proximity of the perforation with the recurrent right laryngeal nerve. Tisseel was applied over the repair. He recovered without further complications. Conclusion: Sudden onset neck swelling post thyroidectomy in the context of significant scaring from radiotherapy, should raise the suspicion of surgical emphysema in the neck patients and confirmed with plain x-ray. Such patients should have multidisciplinary tertiary care. Highlights:

Acute bilateral vocal cord palsy (BLVCP) is an airway emergency. Elucidating the underlying cause is imperative to enable appropriate management. Vincristine-related neurotoxicity is a potentially reversible cause of BLVCP and is rarely described in the literature. We report a case of a 65-year-old man who presented with acutely worsening dyspnoea and stridor following his fifth cycle of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy for hematological malignancy. His airway limitation was managed with supportive measures until he was able to compensate, at which point he was discharged home. His chemotherapy regimen was altered and he underwent serial examinations until he regained full vocal cord mobility at three months following his initial presentation. Through reporting this case, we hope to raise awareness of the potential for vincristine to cause sudden BLVCP and resultant airway deterioration, as well as emphasize the reversible nature of the condition with prompt cessation of therapy.

Objective: The center of excellence model of health care hypothesizes that increased volume in a specialized center will lead to better and more affordable care. We sought to characterize the volume-outcome data for surgically treated sinonasal and skull base tumors and (chemo) radiation-treated nasopharyngeal malignancy. Design: Systematic review of the literature. Setting: This review included national database and multi-institutional studies published between 1990 and 2019. Participants: PubMed was interrogated for keywords “hospital volume,” “facility volume,” and outcomes for “Nasopharyngeal carcinoma,” “Sinonasal carcinomas,” “Pituitary Tumors,” “Acoustic Neuromas,” “Chordomas,” and “Skull Base Tumors” to identify studies. Single-institution studies and self-reported surveys were excluded. Main outcome measures: The main outcome of interest in malignant pathologies was survival; and in benign pathologies it was treatment-related complications. Results: A total of 20 studies met inclusion criteria. The average number of patients per study was 4,052, and ranged from 394 to 9,950 patients. Six of seven studies on malignant pathology demonstrated improved survival with treatment in high volume centers and one showed no association with survival. Ten of thirteen studies on benign disease showed reduced risk of complications, while one study demonstrated both an increased and decreased association of complications. Two studies showed no volume-outcome associations. Conclusion: This systematic review demonstrates that a positive volume–outcome relationship exists for most pathologies of the skull base, with some exceptions. The relative dearth of literature supports further research to understand the effect of centralization of care on treatment outcomes. Podium presentation at the National American Skull Base Surgery (NASBS) Annual Meeting on February 7^th, 2020 in San Antonio, TX. ^* Stephanie Flukes and Rahul K. Sharma are co-first authors Received: 02 March 2020 Accepted: 25 September 2020 Publication Date: 19 January 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Background and Objectives: Total laryngectomy in thyroid cancer is controversial. Functional and oncologic outcomes are needed to inform surgical indications in this population.Methods: A retrospective cohort study was performed at a tertiary referral center from 1997 to 2018 to identify patients with a diagnosis of thyroid carcinoma who underwent total laryngectomy. Complications, survival outcomes, and functional outcomes were analyzed.Results: Thirty patients met the inclusion criteria. The mean age was 62 years (range, 30–88 years) and the male‐to‐female ratio was 1:2.75. The most common diagnosis was well‐differentiated thyroid cancer (53.3%), followed by poorly differentiated (30%) and anaplastic (16.7%). Total laryngectomy was performed with a 10% rate of Clavien–Dindo Grade III–V complications. The median overall survival was 40 months (range, 1–237). Five‐year overall survival was 39.5% and disease‐specific survival was 51.1%. Locoregional control was achieved in 80.0% of patients. Twelve months postoperatively, 100% of surviving patients were taking oral intake and 86.4% had a self‐reported functional voice.Conclusion: Total laryngectomy for locally advanced thyroid cancer is safe and provides acceptable rates of locoregional control. While the risk of distant metastases remains high, advances in systemic therapy may justify aggressive local control strategies to improve the quality of life.