Strategies of airway management for head and neck photo-dynamic therapy.

INTRODUCTION: Photodynamic therapy (PDT) is a minimally invasive treatment modality which has great clinical implications, especially in head and neck oncology. Post-operative swelling is a well-documented consequence of PDT. It is paramount the airway remains patent for these patients. A tracheostomy remains the gold standard treatment modality for base of tongue tumours susceptible to post operative PDT inflammation, which can lead to a compromised airway. We have carried out a retrospective study to outline the airway management strategies employed for head and neck cancer patients treated with PDT and suggest recommendations for future management. MATERIALS AND METHODS: This retrospective clinical study utilises 88 patients (53 males and 35 females) treated at the UCLH Head and Neck Center, London (between 2006 and 2013), for treatment of various lesions with superficial and/or interstitial PDT, when the airway could potentially be compromised. RESULTS: Of the 88 patients selected 60 had interstitial PDT (iPDT) and 13 had superficial PDT (sPDT). Fifteen patients were treated with both iPDT and sPDT. Among the iPDT patients 19 had a trachestomy; two patients a Quicktrach; four a Cook Airway Exchange Catheter (CEAC); one a percutaneous tracheostomy; one a needle tracheostomy and 33 patients did not receive any temporary airway pathways. Among the sPDT patients two had a trachestomy. Although the majority of patients did not suffer any major incidents, one sPDT patient required an emergency tracheostomy two days post-operatively. CONCLUSION: Airway management is vital when planning PDT treatment for tongue based tumours. Consider a more conventional approach when the lesion being targeted is located at a higher risk site: Floor of mouth/posterior tongue/tongue base or when multiple oral sites are being treated.

International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System.

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma.

INTRODUCTION: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. METHODS: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763). RESULTS: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD). CONCLUSIONS: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

Thyroid Storm in Head and Neck Emergency Patients.

BACKGROUND: Thyroid storm is a rare but life-threatening emergency that prompts urgent intervention to halt its potentially disastrous outcomes. There is not much literature available on thyroid storm in head neck trauma and non-thyroid/parathyroid head neck surgery. Due to rarity of thyroid storm in head and neck trauma/surgery patients, its diagnosis becomes challenging, is often misdiagnosed and causes delay in the diagnosis and management. Therefore, the aim of this work was to compile, analyze and present details to develop a consensus and augment available literature on thyroid storm in this group of patients. MATERIALS AND METHODS: A comprehensive literature search of the last 30 years was performed on PUBMED/MEDLINE, EMBASE, CINAHL and Science Citation Index for thyroid storm using MeSH words and statistical analyses were performed. RESULTS: Seven articles describing seven cases of thyroid storm were reviewed. All patients required medical management and one patient (14.3%) required adjunctive surgical management. Burch and Wartofsky Diagnostic criteria for thyroid storm were used in diagnosis of 42% patients. Time of diagnosis varied from immediately upon presentation to formulating a retrospective diagnosis of having a full-blown thyroid storm at 4 days post presentation. It was misdiagnosed and unthought of initially in majority of these cases, (71.4%) were not diagnosed in the first day of hospital stay. CONCLUSION: Early recognition of thyroid storm in head and neck patients markedly reduce morbidity/mortality. Albeit unexpected, it should be ruled out in any symptomatic head and neck trauma or post-surgery patient.

Tracheostomy intervention in intubated COVID positive patients: A survey of current clinical practice among ENT surgeons.

INTRODUCTION: The COVID-19 pandemic has resulted in an unprecedented need for critical care intervention. Prolonged intubation and mechanical ventilation has resulted in the need for tracheostomy in some patients. The purpose of this international survey was to assess optimal timing, technique and outcome for this intervention. METHODS: An online survey was generated. Otorhinolaryngologists from both the United Kingdom and Abroad were polled with regards to their experience of tracheostomy in COVID-19 positive ventilated patients. RESULTS: The survey was completed by 50 respondents from 16 nations. The number of ventilated patients totalled 3403, on average 9.7% required a tracheostomy. This was on average performed on day 14 following intubation. The majority of patients were successfully weaned (mean 7.4 days following tracheostomy). CONCLUSION: The results of this brief survey suggest that tracheostomy is of benefit in selected patients. There was insufficient data to suggest improved outcomes with either percutaneous vs an open surgical technique.

Factors affecting swallowing outcomes after total laryngectomy: Participant self-report using the swallowing outcomes after laryngectomy questionnaire.

BACKGROUND: Little is known about what factors affect patient-reported swallowing outcome after total laryngectomy. We explored whether patient demographics, surgical variables, use of adjuvant treatment, and time since surgery were associated with patient-reported swallowing outcome. METHODS: Cross-sectional study of laryngectomees in eight UK hospitals. Demographic, treatment, and surgical variables were drawn from medical notes. The swallowing outcomes after laryngectomy (SOAL) questionnaire captured perceived swallowing outcome. RESULTS: Two hundred and twenty one participants had complete data on treatment-related variables. In regression analysis, having a free jejunum flap repair and requiring chemoradiation were the only two variables that added significantly to the model of worse self-reported swallowing outcome (R2 adjusted = .23, P < .001). CONCLUSION: The SOAL is a sensitive measure of self-reported swallowing outcome after laryngectomy. Type of surgical closure and the type of additional treatment influenced the swallowing outcome reported by patients. Changes in perceived swallowing function need to be routinely evaluated to inform clinical decision-making and intervention.

Frequent HPV-independent p16/INK4A overexpression in head and neck cancer.

OBJECTIVES: p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven. MATERIALS AND METHODS: We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression. RESULTS: While p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (-) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (-) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (-)/p16-high tumors. CONCLUSIONS: RPPA data suggest high p16 protein expression in many HPV (-) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1.

Regonising Ear, Nose and Throat Conditions in the Dentist's Chair.

The dentist's chair presents an opportunity to pick up ear nose and throat lesions, by virtue of the close proximity of the anatomical areas. Urgent two-week wait referral can expedite assessment and management of head and neck malignancies, thereby improving the prognosis. In this paper, we attempt to highlight the ear, nose and throat (ENT) conditions that need a two week referral, as well as the benign head and neck lesions which can potentially be picked up in a dentist's chair.

Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma.

BACKGROUND: Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) represents a distinct clinical and epidemiological condition compared with HPV-negative (HPV-) HNSCC. To test the possible involvement of epigenetic modulation by HPV in HNSCC, we conducted a genome-wide DNA-methylation analysis. METHODS: Using laser-capture microdissection of 42 formalin-fixed paraffin wax-embedded (FFPE) HNSCCs, we generated DNA-methylation profiles of 18 HPV+ and 14 HPV- samples, using Infinium 450 k BeadArray technology. Methylation data were validated in two sets of independent HPV+/HPV- HNSCC samples (fresh-frozen samples and cell lines) using two independent methods (Infinium 450 k and whole-genome methylated DNA immunoprecipitation sequencing (MeDIP-seq)). For the functional analysis, an HPV- HNSCC cell line was transduced with lentiviral constructs containing the two HPV oncogenes (E6 and E7), and effects on methylation were assayed using the Infinium 450 k technology. RESULTS AND DISCUSSION: Unsupervised clustering over the methylation variable positions (MVPs) with greatest variation showed that samples segregated in accordance with HPV status, but also that HPV+ tumors are heterogeneous. MVPs were significantly enriched at transcriptional start sites, leading to the identification of a candidate CpG island methylator phenotype in a sub-group of the HPV+ tumors. Supervised analysis identified a strong preponderance (87%) of MVPs towards hypermethylation in HPV+ HNSCC. Meta-analysis of our HNSCC and publicly available methylation data in cervical and lung cancers confirmed the observed DNA-methylation signature to be HPV-specific and tissue-independent. Grouping of MVPs into functionally more significant differentially methylated regions identified 43 hypermethylated promoter DMRs, including for three cadherins of the Polycomb group target genes. Integration with independent expression data showed strong negative correlation, especially for the cadherin gene-family members. Combinatorial ectopic expression of the two HPV oncogenes (E6 and E7) in an HPV- HNSCC cell line partially phenocopied the hypermethylation signature seen in HPV+ HNSCC tumors, and established E6 as the main viral effector gene. CONCLUSIONS: Our data establish that archival FFPE tissue is very suitable for this type of methylome analysis, and suggest that HPV modulates the HNSCC epigenome through hypermethylation of Polycomb repressive complex 2 target genes such as cadherins, which are implicated in tumor progression and metastasis.

Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors.

BACKGROUND: Human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is an emerging disease, representing a distinct clinical and epidemiological entity. Understanding the genetic basis of this specific subtype of cancer could allow therapeutic targeting of affected pathways for a stratified medicine approach. METHODS: Twenty HPV+ and 20 HPV- laser-capture microdissected oropharyngeal carcinomas were used for paired-end sequencing of hybrid-captured DNA, targeting 3,230 exons in 182 genes often mutated in cancer. Copy number alteration (CNA) profiling, Sequenom MassArray sequencing and immunohistochemistry were used to further validate findings. RESULTS: HPV+ and HPV- oropharyngeal carcinomas cluster into two distinct subgroups. TP53 mutations are detected in 100% of HPV negative cases and abrogation of the G1/S checkpoint by CDKN2A/B deletion and/or CCND1 amplification occurs in the majority of HPV- tumors. CONCLUSION: These findings strongly support a causal role for HPV, acting via p53 and RB pathway inhibition, in the pathogenesis of a subset of oropharyngeal cancers and suggest that studies of CDK inhibitors in HPV- disease may be warranted. Mutation and copy number alteration of PI3 kinase (PI3K) pathway components appears particularly prevalent in HPV+ tumors and assessment of these alterations may aid in the interpretation of current clinical trials of PI3K, AKT, and mTOR inhibitors in HNSCC.

The palliative role of PDT in recurrent advanced nasopharyngeal carcinoma: case series.

We report on the application of photodynamic therapy in the management of recurrent advanced carcinoma of the nasopharynx. A selected cohort of 7 patients, only suitable for palliative therapy, was offered this modality to assess the palliative role of PDT. All 7 patients had at least 2 previous recurrences, which were managed with surgery and chemoradiotherapy but ultimately failed to respond. PDT was offered after careful discussion at a multidiscipline meeting. The photosensitiser "mTHPC" was introduced intravenously 96 h prior to delivering the light with nasoendoscopic guidance. Six patients' symptoms were reduced markedly post photodynamic therapy. Five patients have to had another round of treatment which was found to be as effective as the first round in terms of controlling disease progression as well as symptoms. Magnetic resonance images showed variable reduction of tumour volume with the majority of the patients having moderate to significant response. Photodynamic therapy was very successful palliative therapy for this small group of recurrent advanced nasopharyngeal cancer patients.

Endoscopic management of an internal laryngopyocele presenting with acute airway obstruction.

Statement of Problem. Laryngocele is a rare laryngeal disease, where there is an abnormal dilatation of the saccule of the laryngeal ventricle. It can either be internal or external, and a laryngopyocele is a rare complication of this anomaly. Internal laryngopyoceles can prove difficult to manage, as they often present with airway compromise. Method of Study. Case Report. Results. We present a case of a laryngopyocele that was successfully managed with suspension laryngoscopy and endoscopic marsupialisation and resection. To our knowledge, this is the first such case described in the literature. Conclusions. Surgical drainage of a laryngopyocele via the external approach is well documented in the literature. We feel that endoscopic resection of laryngopyoceles in an emergency situation is a viable alternative and also prevents the associated surgical morbidity.

Subglottic carcinoma treated with surgery and adjuvant photodynamic therapy.

Subglottic cancers are extremely rare as a primary malignancy representing <8% of all laryngeal cancers. Typical age at presentation is in the 5th decade. There are three main types of subglottic carcinoma: adenocarcinoma, mucoepidermoid and adenoid cystic carcinoma. We present a rare case of subglottic cancer treated with surgery and adjuvant photodynamic therapy.

Comparison of long term results after Ho:YAG and diode laser treatment of hyperplastic inferior nasal turbinates.

BACKGROUND AND OBJECTIVE: Various laser systems have been used to reduce the volume of hyperplastic inferior nasal turbinates during the last 25 years. Although there are many studies reporting the clinical results immediately after laser treatment, there are only a few describing long-term results. Therefore, a clinical study was performed to assess and to compare the long-term outcome of both endonasal Ho:YAG and endonasal diode laser-assisted turbinate surgery. STUDY DESIGN/MATERIALS AND METHODS: In the first treatment group, a total of 80 patients (allergic rhinitis (46%) and vasomotor rhinitis (54%)) suffering from nasal obstruction due to hyperplastic inferior nasal turbinates were treated by a pulsed Ho:YAG laser emitting light at a wavelength of lambda = 2,100 nm (pulse energy: 0.8-1.2 J/pulse, repetition rate: 4-8 Hz) under local anesthesia. In the second group, an additional 113 patients (allergic rhinitis (52%) and vasomotor rhinitis (48%)) were treated by means of a continuous wave GaAlAs-diode laser emitting light at a wavelength of lambda = 940 nm (power: 8-10 W). The treatment time was 3-10 minutes per turbinate and the nasal cavities were left unpacked following the procedure. The study concerning long-term effects was conducted using a standardized questionnaire, allergy test, and rhinomanometry within a follow-up period of 6 month and after 3 years. All patients were refractory to conservative medical treatment prior to laser treatment. RESULTS: Three years after laser treatment, a subjective improvement of nasal airflow had been described by the patients in 67.5% after Ho:YAG- and in 74.4% after diode laser treatment. Rhinomanometry revealed a significant improvement of the nasal airflow at both 6 months and 3 years after the laser treatment as compared to the preoperative data. Side effects like nasal dryness and pain were rare (<5%) and occurred only during the first weeks after the intervention. After diode laser treatment, patients showed nasal obstruction due to postoperative edema and nasal crusting during the first 3-4 weeks, whereas patients from the Ho:YAG laser group described these symptoms only for a period of 1-2 weeks. CONCLUSION: Both Ho:YAG- and diode laser treatment, which are performed as an outpatient procedure under local anesthesia, show promising long-term results. It has therefore, developed to become a time and cost-effective treatment modality in endonasal laser surgery at our institution. While short-term differences concerning the healing process after Ho:YAG- compared to diode-laser treatment could be ascertained according to the subjective and objective evaluation, no significant long-term differences between the two investigated groups could be observed.