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.

Acute otitis externa: Consensus definition, diagnostic criteria and core outcome set development.

OBJECTIVE: Evidence for the management of acute otitis externa (AOE) is limited, with unclear diagnostic criteria and variably reported outcome measures that may not reflect key stakeholder priorities. We aimed to develop 1) a definition, 2) diagnostic criteria and 3) a core outcome set (COS) for AOE. STUDY DESIGN: COS development according to Core Outcome Measures in Effectiveness Trials (COMET) methodology and parallel consensus selection of diagnostic criteria/definition. SETTING: Stakeholders from the United Kingdom. SUBJECTS AND METHODS: Comprehensive literature review identified candidate items for the COS, definition and diagnostic criteria. Nine individuals with past AOE generated further patient-centred candidate items. Candidate items were rated for importance by patient and professional (ENT doctors, general practitioners, microbiologists, nurses, audiologists) stakeholders in a three-round online Delphi exercise. Consensus items were grouped to form the COS, diagnostic criteria, and definition. RESULTS: Candidate COS items from patients (n = 28) and literature (n = 25) were deduplicated and amalgamated to a final candidate list (n = 46). Patients emphasised quality-of-life and the impact on daily activities/work. Via the Delphi process, stakeholders agreed on 31 candidate items. The final COS covered six outcomes: pain; disease severity; impact on quality-of-life and daily activities; patient satisfaction; treatment-related outcome; and microbiology. 14 candidate diagnostic criteria were identified, 8 reaching inclusion consensus. The final definition for AOE was 'diffuse inflammation of the ear canal skin of less than 6 weeks duration'. CONCLUSION: The development and adoption of a consensus definition, diagnostic criteria and a COS will help to standardise future research in AOE, facilitating meta-analysis. Consulting former patients throughout development highlighted deficiencies in the outcomes adopted previously, in particular concerning the impact of AOE on daily life.

Earfold Implantable Clip System for Correction of Prominent Ears: Analysis of Safety in 403 Patients.

BACKGROUND: The Earfold system, a new treatment for the correction of prominent ears, consists of 3 components: the Earfold implant, the Earfold introducer, and the Prefold positioner. METHODS: This is an interim report based on an ongoing analysis of safety in a series of patients treated for prominent ears with the Earfold implant between February 2013 and September 2014. Safety was assessed based on adverse event reports and the need for implant revision; follow-up is ongoing. RESULTS: Seven surgeons used 1,200 Earfold implants to treat 403 patients (ages, 7-70 years; 63% male); the time since the initial implant procedure now ranges from 30 to 48 months. To date, 145 patients (36%) have returned for a follow-up visit (mean, 7.7 months [range, 1-34 months]). Adverse events requiring intervention have affected 39 of 403 (9.7%) patients; these include implant revisions (n = 17 [4.2%], most often due to implant visibility), skin erosion over the implant (n = 15 [3.7%]), and infection (n = 7 [1.7%]). Bleeding, recurrence of prominence, hematoma, deformity, or adverse scarring did not occur. CONCLUSIONS: This interim analysis has shown that Earfold prominent ear correction system is associated with relatively few adverse events that require intervention; a small number of patients experienced infection, implant extrusion, or implant visibility that required revision. Most adverse events were related to either patient selection or technical errors at implantation. It is expected that with continued use of Earfold by surgeons experienced in otoplasty, the adverse event incidence will decrease.

Sleep nasendoscopy: a 10-year retrospective audit study.

Sleep nasendoscopy was conceived at the Royal National Throat, Nose and Ear Hospital, UK in 1991, and has remained fully implemented in patient selection for targeted treatment of the spectrum of sleep-disordered breathing. The senior authors (B.T.K. and P.B.) have been performing sleep nasendoscopy together for over 10 years, and we look back at their decade's experience. A retrospective audit study based on case notes was performed over a 10-year period (1995-2005) in a tertiary-referral practice setting. Case notes were retrieved on all patients who had undergone sleep nasendoscopy during the study period, and agreed data were extracted and analyzed. A total of 2,485 sleep nasendoscopies were performed in patients with a mean age of 44.1 years, a 4:1 male preponderance, and a mean body mass index of 27.3 kg m(-2). Sleep nasendoscopy grading correlated well with apnoea-hypopnoea index and mean oxygen desaturation. Such grading helped us define and discuss treatment options with patients. After a median follow-up period of 518 days, 72% of patients reported feeling better; 26% of patients reported no change; and only 2% of patients reported feeling worse after treatment. Sleep nasendoscopy has proved to be a useful adjunctive method to identify the anatomical site of snoring, not to mention upper airway collapse, and remains integral to our tertiary-referral practice. It has allowed us quality assessment of the dynamic anatomy of sleep-disordered breathing that most closely and cost-effectively simulates the natural situation of patients. And for targeted treatment, such assessment has been fundamental.

Noise-induced hearing loss: a modern epidemic?

Hearing loss is an increasingly common problem in the UK, and noise-induced hearing loss is the second most common acquired cause. There is a greater burden on the younger population, as recreational noise exposure is an important contributor. New damaging hearing behaviours have emerged including loud music exposure at concerts, nightclubs and via personal music players. The mechanism of damage is thought to involve many diverse pathways, which include oxidative damage, mechanical shearing forces and glutamate excitotoxicity. Although no current treatment exists to reverse the damage caused, these pathways can be targeted by agents that are being trialled for use in post-exposure treatment and prevention, with conflicting results. Other preventative strategies are important in addressing damaging hearing behaviours, including 'safe listening' promotion with advocacy materials for young adults, and promoting safe listening devices.

Are randomised controlled trials involving adenotonsillectomy well reported?

INTRODUCTION: Evidence-based medicine guides clinical practice. Currently, the evidence base on adenotonsillectomy is under scrutiny to establish clinical guidelines. It is therefore important that reports of clinical trials are of high quality. Guidance on reporting of randomised controlled trials (RCTs) are available in the Consolidated Standards for Reporting Trials (CONSORT) statement first published in 1996 and revised in 2001 and 2010. METHODS: A review of randomised controlled trials on adenotonsillectomy published after 2001 was undertaken. Each report was systematically assessed using the checklist of items from the CONSORT statement. RESULTS: Twenty-five trials were identified. All trials, except one, were identified as a randomised controlled trial by title or abstract. Twenty percent of trials reported a sample size calculation. A third of trials reported their method of generating a random allocation sequence. Similarly, a third stated the method of implementing the random allocation. A fifth of trials reported a clear flow of trial participants, with only a single trial reporting this with the aid of a diagram. CONCLUSION: This review shows the quality of reporting needs to be improved. Critical appraisal of poorly reported trials may result in erroneous conclusions, even though these trials may have been carried out with rigorous adherence to a protocol of high standard. Authors of clinical trial reports should be encouraged to consult the CONSORT statement.

The magnificent seven: a history of modern thyroid surgery.

In the mid-19th century, thyroid surgery was regarded as a "proceeding by no means to be thought of" in Britain, "foolhardy" in Europe, and "horrid butchery" in America. By the mid-20th century, thyroid surgery was amongst the most efficient and safest of operations. This transition of modern thyroid surgery over a century was brought about by seven surgeons. The lessons of Theodor Billroth, Theodor Kocher, William Halsted, Charles Mayo, George Crile, Frank Lahey and Thomas Dunhill are to be forever relearned and respected. Let us remember this pantheon of pioneers, these "Magnificent Seven".