Recommendations for head and neck surgical oncology practice in a setting of acute severe resource constraint during the COVID-19 pandemic: an international consensus.

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

Differential mechanisms of CDKN2A (p16) alteration in oral tongue squamous cell carcinomas and correlation with patient outcome.

CDKN2A (p16) disruption is reported as a frequent event in head and neck squamous cell carcinomas that confers poor prognosis. We investigated the frequency of different potential mechanisms of CDKN2A inactivation in oral tongue squamous cell carcinomas (OTSCC) and their impact on patient outcome. From a cohort of 153 OTSCC patients, 131 formalin fixed paraffin embedded blocks of pre-treatment primary tumours were suitable for further molecular analysis. We assessed CDKN2A (p16) levels by immunohistochemistry (IHC), promoter methylation status by methylation-sensitive high resolution melting, mutation status by Sanger sequencing, gene copy number variation by fluorescence in situ hybridisation, and correlated these with patient outcome. We found that the majority of OTSCC did not overexpress p16 (110/116, 95%), assessed by IHC. The frequency of CDKN2A mutations was 20% (21/103), homozygous loss was 7% (7/97), hemizygous loss 31% (30/97), and promoter methylation was 18% (20/113). We found no evidence of these mechanisms in 24/106 (23%) p16 IHC negative tumours. No significant correlation was identified between any potential mechanism of CDKN2A inactivation and clinical features, including smoking status and age. There was a non-significant trend for worse overall survival for p16 IHC negative patients versus positive patients (HR = 1.81, 95% CI = 0.44-7.47, p = 0.40). No relationship was found between mechanisms of CDKN2A disruption and patient outcome. In conclusion, we demonstrate that CDKN2A alteration is a frequent event in OTSCC tumourigenesis. However, no correlation was identified between different potential mechanisms of CDKN2A disruption and clinical characteristics or patient outcome.

Synovial sarcoma of the pharynx causing airway obstruction.

This is the first reported Australian case of synovial sarcoma of the pharynx. A 29-year-old man had a large hypopharyngeal mass excised and received radiotherapy and chemotherapy. No recurrence was seen 12 months later.

Novel Multidisciplinary Salivary Gland Society (MSGS) Questionnaire: An International Consensus.

OBJECTIVES: First, establishment and validation of a novel questionnaire documenting the burden of xerostomia and sialadenitis symptoms, including quality of life. Second, to compare two versions regarding the answering scale (proposed developed answers Q3 vs. 0-10 visual analogue scale Q10) of our newly developed questionnaire, in order to evaluate their comprehension by patients and their reproducibility in time. STUDY DESIGN: The study is a systematic review regarding the evaluation of the existing questionnaire and a cohort study regarding the validation of our new MSGS questionnaire. MATERIALS AND METHODS: A Multidisciplinary Salivary Gland Society (MSGS) questionnaire consisting of 20 questions and two scoring systems was developed to quantify symptoms of dry mouth and sialadenitis. Validation of the questionnaire was carried out on 199 patients with salivary pathologies (digestive, nasal, or age-related xerostomia, post radiation therapy, post radioiodine therapy, Sjögren's syndrome, IgG4 disease, recurrent juvenile parotitis, stones, and strictures) and a control group of 66 healthy volunteers. The coherence of the questionnaire's items, its reliability to distinguish patients from healthy volunteers, its comparison with unstimulated sialometry, and the time to fill both versions were assessed. RESULTS: The novel MSGS questionnaire showed good internal coherence of the items, indicating its pertinence: the scale reliability coefficients amounted to a Cronbach's alpha of 0.92 for Q10 and 0.90 for Q3. The time to complete Q3 and Q10 amounted, respectively, to 5.23 min (±2.3 min) and 5.65 min (±2.64 min) for patients and to 3.94 min (±3.94 min) and 3.75 min (±2.11 min) for healthy volunteers. The difference between Q3 and Q10 was not significant. CONCLUSION: We present a novel self-administered questionnaire quantifying xerostomia and non-tumoral salivary gland pathologies. We recommend the use of the Q10 version, as its scale type is well known in the literature and it translation for international use will be more accurate. Laryngoscope, 132:322-331, 2022.

Outcomes of dental and craniofacial osseointegrated implantation in head and neck cancer patients.

BACKGROUND: Treatment of head and neck cancer may result in disfiguring and debilitating anatomical changes. Osseointegrated implants may be used in these patients to facilitate attachment of implant-retained dentures or cosmetic prostheses. METHODS: A retrospective audit was performed, reviewing the treatment of patients who received dental or craniofacial osseointegrated implants during treatment of head and neck cancer. RESULTS: One hundred sixty implants were inserted in 54 patients with oral, nasal, orbital, or auricular defects. Overall, 85% of implants were successful after mean follow-up of 25.7 months. The brand of implant used was shown to impart a statistically significant implant survival difference, and orbital implants had poorer survival compared to nonorbital implants. There was a statistical insignificant implant survival advantage in both nonsmokers and patients who did not undergo radiotherapy. CONCLUSIONS: Dental and craniofacial osseointegrated implants may be reliably used in patients with head and neck cancer. However, further research is required to clarify the role of smoking in osseointegrated implant failure.

Evolving strategies for the treatment of valvular heart disease: Preclinical and clinical pathways for percutaneous aortic valve replacement.

To decrease the morbidity associated with conventional surgery for calcific aortic stenosis, there has been increasing interest in catheter-based treatment using a stent or frame mounted bioprosthetic valve. Critical to its success is knowledge of pathoanatomy, risk of embolization of calcific debris, and issues associated with device anchoring and paravalvular leaks. In the absence of a chronic animal model of aortic stenosis, development of a catheter-based device has been an iterative process based on experimental and early clinical data gathered abroad, where marketing may be permitted with less clinical data than required in the United States. This process has persuaded many companies to circumvent the time delays occasioned by the FDA regulatory validation of iterative design changes by performing initial studies outside the United States. Because percutaneous aortic valve replacement is considered a Class III device, premarket approval, including defining the patient population, inclusion and exclusion criteria, control population, and interpretable clinical endpoints, is required. In the early clinical experience, percutaneous aortic valve replacement has been directed at high-risk patients who were considered "very poor" or "non-surgical" candidates. Defining and identifying patients for the clinical trial may be challenging, in part because of the difficult selection of an appropriate control group, e.g., conventional aortic valve replacement, best medical management, and/or balloon valvuloplasty.

Review of epiglottitis in the post Haemophilus influenzae type-b vaccine era.

BACKGROUND: This study reviewed the demographics, presentation, management, complications and outcomes of acute epiglottitis post Haemophilus influenzae type-b vaccine introduction in Australia. METHODS: Retrospective review of acute epiglottitis at four Victorian tertiary centres from 2011 to 2016 was conducted. Patient characteristics, presentation, investigations, management, complications and outcomes were recorded. Subgroup analysis aiming to identify risk factors for patients requiring acute airway management was performed. RESULTS: Eighty-seven adult and six paediatric cases were identified. The most frequent clinical findings in adults were sore throat (88.5%), dysphagia (71.3%), odynophagia (57.5%), dysphonia (56.3%) and fever (55.2%); 75.9% required intensive care unit admission. Airway compromise requiring intubation occurred in 27.6%, with 12.5% of these patients undergoing emergency surgical airways. Stridor, hypoxia, shortness of breath, odynophagia and lymphadenopathy were statistically more frequent amongst cases requiring airway intervention (P < 0.05). Cultures revealed mixed results with no aetiological pattern. H. influenzae type-b was never cultured. Amongst paediatric cases, fever, tachycardia and stridor were frequently observed and all were admitted to intensive care unit. Two of six required intubation and one underwent surgical intervention. There were no deaths, but one patient suffered a hypoxic brain injury. CONCLUSION: Modern epiglottitis is not the disease previously encountered by clinicians. With changing demographics and varying organisms, management is adapting to reflect this. Complications are rare, and symptomatology at presentation aids earlier recognition of patients who may require airway protection.

Functional outcomes following total laryngopharyngectomy.

BACKGROUND: Despite increasing use of laryngeal preserving protocols, laryngopharyngectomy remains the gold standard treatment for locally advanced hypopharyngeal and upper oesophageal tumours and for salvage following failed chemoradiotherapy. Nevertheless, improved perioperative medical care and experience in reconstruction have reduced mortality and improved functional outcomes. METHODS: All patients undergoing total laryngopharyngectomy between July 2001 and July 2006 were prospectively recorded in a head and neck database. Demographics and functional outcomes were recorded. RESULTS: Eighteen patients underwent laryngopharyngectomies with 5 having failed chemoradiotherapy and 13 presented with locally advanced tumours. Patients were reconstructed using free jejunal interposition if the lower anastomosis was in the neck (50%). They developed early fistulas (33%), late strictures (33%) and 44% spoke with a tracheo-oesophageal puncture, the rest with an electrolarynx. If the lower anastomosis was below the manubrium, patients required a gastric pull-up (38.9%). Gastric pull-up patients had fewer fistulas but more number of chest complications. More gastric pull-up patients tolerated solid diet and 43% managed oesophageal speech, the remainder using an electrolarynx. Overall, 88.9% of jejunums and 100% of gastric pull-ups tolerated oral alimentation and 100% used verbal communication. During a mean follow up of 34 months, 7 patients (38.9%) died; four patients died of local recurrence, two of distant metastases and one of unrelated causes. CONCLUSION: Surgical treatment of neoplasms of the hypopharynx and cervical oesophagus is technically demanding and involves careful postoperative care to manage complications. Despite having a poor tumour-related prognosis, laryngopharyngectomy may be carried out in selected patients with low mortality and acceptable functional and survival results.

Quantitative methodology is critical for assessing DNA methylation and impacts on correlation with patient outcome.

BACKGROUND: DNA hypermethylation is reported as a frequent event and prognostic marker in head and neck squamous cell carcinomas (HNSCC). Methylation has been commonly assessed with non-quantitative methodologies, such as methylation-specific PCR (MSP). We investigated previously reported hypermethylated genes with quantitative methodology in oral tongue squamous cell carcinomas (OTSCC). RESULTS: The methylation status of 12 genes in 115 OTSCC samples was assessed by one or more of three quantitative analyses: methylation sensitive high resolution melting (MS-HRM), sensitive-melting analysis after real time-methylation specific PCR (SMART-MSP), and bisulfite pyrosequencing. In contrast to much of the literature, either no or infrequent locus-specific methylation was identified by MS-HRM for DAPK1, RASSF1A, MGMT, MLH1, APC, CDH1, CDH13, BRCA1, ERCC1, and ATM. The most frequently methylated loci were RUNX3 (18/108 methylated) and ABO (22/107 methylated). Interrogation of the Cancer Genome Atlas (TCGA) HNSCC cohort confirmed the frequency of significant methylation for the loci investigated. Heterogeneous methylation of RUNX3 (18/108) and ABO (22/107) detected by MS-HRM, conferred significantly worse survival (P = 0.01, and P = 0.03). However, following quantification of methylation levels using pyrosequencing, only four tumors had significant quantities (>15%) of RUNX3 methylation which correlated with a worse patient outcome (P <0.001), while the prognostic significance of ABO hypermethylation was lost. RUNX3 methylation was not prognostic for the TCGA cohort (P = 0.76). CONCLUSIONS: We demonstrated the critical need for quantification of methylation levels and its impact on correlative analyses. In OTSCC, we found little evidence of significant or frequent hypermethylation of many loci reported to be commonly methylated. It is likely that previous reports have overestimated the frequency of significant methylation events as a consequence of the use of non-quantitative methodology.

Frequency of fibroblast growth factor receptor 1 gene amplification in oral tongue squamous cell carcinomas and associations with clinical features and patient outcome.

OBJECTIVES: Novel therapies are required for patients with recurrent or metastatic oral tongue squamous cell carcinoma (OTSCC). Fibroblast Growth Factor Receptor 1 (FGFR1) amplification frequently occurs in squamous cell carcinoma of the lung and represents a novel druggable therapeutic target in this and other malignancies. This study examined the frequency and clinical associations of FGFR1 amplification in OTSCC. MATERIALS AND METHODS: The frequency of FGFR1 amplification determined by fluorescence in situ hybridization was evaluated in a cohort of 123 OTSCC patients. Associations of FGFR1 amplification with clinical characteristics and outcome were determined. RESULTS: FGFR1 gene amplification was present in 9.3% (10/107) of cases and was significantly associated with smoking status (P = 0.03). FGFR1 amplification was seen more commonly in males (9/10 amplified cases male, P = 0.16) and there were no associations with age, stage, T stage, nodal status, alcohol history or performance status (all P>0.05). Outcome was not significantly different between FGFR1 amplified and non-amplified patients. CONCLUSIONS: Copy number variations of the FGFR1 gene occur in a subset of OTSCC with approximately 10% of cases showing amplification of the gene. FGFR1 amplification may represent a therapeutic target in OTSCC.

Chondroblastoma of the temporal bone: a case series, review, and suggested management strategy.

Chondroblastoma of the temporal bone is a rare condition. Chondroblastomas account for less than 1% of primary bone tumors, and those involving the temporal bone represent a tiny fraction of these tumors with most arising from the knee, rib, and pelvis. We present a case series of two patients who presented with chondroblastomas of the temporal bone over a period of 8 years to the St. Vincent's Hospital in Melbourne, Victoria, Australia. In particular, we outline the presenting complaint, diagnostic imaging undertaken, and the importance of preoperative histopathology in coming to the diagnosis and subsequent resection undertaken. A review of the current literature is presented with a suggested management strategy for these tumors.

Larynx preservation with primary non-surgical treatment for loco-regionally advanced larynx cancer.

INTRODUCTION: The objective of this paper was to review the results of primary non-surgical treatment with the aim of larynx preservation for loco-regionally advanced larynx cancer (LALC). METHODS: All patients with LALC presenting between January 2002 and December 2006 who were selected for primary non-surgical treatment were included in this study. RESULTS: There were 60 patients, 48% with stage III and 52% with stage IV disease. The median follow-up of living patients was 41 months. Larynx preservation with local disease control was achieved in 83% and 77% of patients at 3 and 5 years, respectively. Failure-free survival at 3 and 5 years was 66% and 59%, respectively, and overall survival was 67% and 45%, respectively. All patients with larynx preservation had a functional voice. Two patients became feeding tube dependant. Thirty-nine percent of all deaths were unrelated to LALC. CONCLUSIONS: Primary non-surgical treatment achieves high rates of larynx preservation with a low rate of severe complications but overall survival remains disappointing.