Breathing pattern disorder in chronic rhinosinusitis with severe asthma: nasal obstruction and polyps do not increase prevalence.

OBJECTIVES: Chronic rhinosinusitis (CRS) with severe asthma are associated with breathing pattern disorder (BPD). Mouth breathing is a sign of breathing pattern disorder, and nose breathing a fundamental part of breathing pattern retraining for BPD. The prevalence of BPD in relation to CRS subtypes and the relationship of nasal obstruction to BPD in CRS and associated severe asthma is unknown. The breathing pattern assessment tool (BPAT) can identify BPD. Our objective was to thus investigate the prevalence of BPD, nasal airflow obstruction and measures of airway disease severity in CRS with (CRSwNP) and without nasal polyps (CRSsNP) in severe asthma. METHODS: We determined whether CRS status, peak nasal inspiratory flow (PNIF) or polyp disease increased BPD prevalence. Demographic factors, measures of airway function and breathlessness in relation to BPD status and CRS subtypes were also evaluated. RESULTS: 130 Patients were evaluated (n = 69 had BPD). The prevalence of BPD in CRS with severe asthma was 53.1%. There was no difference between BPD occurrence between CRSwNP and CRSsNP. The mean polyp grade and PNIF were not statistically different between the BPD and non-BPD group. The presence of nasal polyps did not increase breathlessness. CONCLUSIONS: BPD and CRS are commonly co-associated. CRS status and nasal obstruction per se does not increase BPD prevalence.

Non-Eosinophilic Granulomatous Disease and the Unified Airway.

Granulomatous and vasculitic diseases of the airway may be part of more widespread systemic disease but can occur in isolation. They may present to the ear, nose, and throat (ENT) surgeon initially with vague symptoms that mimic more common chronic inflammatory unified airway conditions, such as rhinitis, chronic rhinosinusitis, and asthma. Early diagnosis is associated with better long-term outcomes, so a high index of suspicion is required. Bloody nasal discharge and crusting are highly suspicious for granulomatous disease, which should also be considered in atypical or recalcitrant disease. A combination of clinical findings, serologic tests, imaging, and histology may be required to confirm the diagnosis..

DNA methylation-based classification of sinonasal tumors.

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs.

Biologicals and Endoscopic Sinus Surgery for Severe Uncontrolled Chronic Rhinosinusitis With Nasal Polyps: An Economic Perspective.

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a chronic disease with a high prevalence and high disease burden, and the lack of a cure. The socioeconomic burden of the disease is substantial and has been disproportionally increasing over past decades. Treatment is aimed at attaining disease control. Traditionally, topical corticosteroids, endoscopic sinus surgery, and oral corticosteroids are used to treat CRSwNP. The advent of biologics has revolutionized CRSwNP treatment, but these drugs are expensive. From an economic standpoint, it is worth debating whether biologics should be employed in patients with severe uncontrolled CRSwNP who fail to attain disease control with current therapies. This clinical commentary review provides an overview of the socioeconomic burden of chronic rhinosinusitis and treatment modalities, compares endoscopic sinus surgery versus biologics for severe CRSwNP, discusses management recommendations, and highlights future needs in this field. New ways to reduce costs of biologic treatments need to be explored to attain cost-effectiveness and provide patients who have severe CRSwNP with adequate treatment.

Biphenotypic sinonasal sarcoma: European multicentre case-series and systematic literature review.

Objective: Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade cancer that was included from the 4th edition of WHO classification of head and neck tumours. The purpose of this study is to analyse clinical behaviour, pattern of recurrences and survival outcomes of this neoplasm. Methods: Retrospective review of patients affected by BSNS who were treated via an endoscopic-assisted approach in 6 European tertiary-care referral hospitals. Cases of BSNS described in literature since 2012 to date were fully reviewed, according to PRISMA guidelines. Results: A total of 15 patients were included. Seven patients were treated via an endoscopic endonasal approach, 4 with endoscopic transnasal craniectomy, and 4 via a cranio-endoscopic approach. Adjuvant treatment was delivered in 2 cases. After a mean follow-up of 27.3 months, systemic metastasis was observed in 1 case; the 5-year overall survival and disease-free survival rates were 100% and 80 ± 17.9%, respectively. Conclusions: BSNS is a locally aggressive tumour with a low recurrence rate and encouraging survival outcomes if properly treated with surgical resection and free margins followed by adjuvant radiotherapy for selected cases. Endoscopic-assisted surgery is safe and effective as an upfront treatment within a multidisciplinary care protocol.

SSTR2 in Nasopharyngeal Carcinoma: Relationship with Latent EBV Infection and Potential as a Therapeutic Target.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor, most commonly located in the pharyngeal recess and endemic to parts of Asia. It is often detected at a late stage which is associated with poor prognosis (5-year survival rate of 63%). Treatment for this malignancy relies predominantly on radiotherapy and/or systemic chemotherapy, which can be associated with significant morbidity and impaired quality of life. In endemic regions NPC is associated with infection by Epstein-Barr virus (EBV) which was shown to upregulate the somatostatin receptor 2 (SSTR2) cell surface receptor. With recent advances in molecular techniques allowing for an improved understanding of the molecular aetiology of this disease and its relation to SSTR2 expression, we provide a comprehensive and up-to-date overview of this disease and highlight the emergence of SSTR2 as a key tumor biomarker and promising target for imaging and therapy.

Chronic rhinosinusitis with and without nasal polyps and asthma: Omalizumab improves residual anxiety but not depression.

BACKGROUND: Chronic rhinosinusitis (CRS) has a high prevalence of anxiety and depression. It is currently uncertain if treatment in patients with CRS with or without nasal polyps (CRSwNP and CRSsNP) has any impact on improving mental health outcomes. The aims here were to document anxiety and depression in patients with severe CRS and asthma already treated with appropriate medical therapy. We then evaluated whether further maximal treatment with omalizumab improved anxiety and/or depression alongside improvements in CRS and coassociated asthma. METHODS: Hospital Anxiety and Depression Scale (HADS) scores along with measures of CRS and asthma severity were recorded according to CRSwNP and CRSsNP status in n = 95 patients with severe CRS and asthma. Of this group, a further n = 23 had omalizumab for associated allergic asthma. Follow-up measures were collected 16 weeks after omalizumab treatment. RESULTS: HADS anxiety and depression prevalence in CRS were 49.47 % and 38.95%, respectively. Within the CRSwNP and CRSsNP group 53.06% and 45.66% had raised HADS-anxiety scores. Abnormal HADS-depression scores were present in 40.82% and 36.95% of the CRSwNP and CRSsNP groups, respectively. Correlations for sinonasal outcome test-22 (SNOT-22) versus HADS total was r = 0.59 p < 0.0001, HADS-anxiety r = 0.56 p < 0.0001 and HADS-depression r = 0.49 p < 0.0001. Omalizumab improved anxiety in CRS (p < 0.0001) regardless of nasal polyp status (CRSwNP p = 0.0042 and CRSsNP p = 0.0078). Depression scores did not improve in either group. SNOT-22 (p = 0.0006), asthma control questionnaire-7 (p = 0.0019) and mini-asthma quality of life questionnaire including emotional function (p = 0.0003 and p = 0.0009, respectively) all improved in both subgroups. CONCLUSION: In CRS and asthma, anxiety scores but not depression improved after omalizumab treatment. Anxiety may be closely related to airway disease severity, but depression may be independent of airway disease itself. If so, a separate mental health care pathway is needed for CRS patients with depression.

Endonasal endoscopic surgery for sinonasal squamous cell carcinoma from an oncological perspective.

Endonasal endoscopic surgery (EES) has been applied to the management of sinonasal (SN) tumors based on recent advances in endoscopic surgical techniques and technologies over the past three decades. EES has been mainly indicated for benign tumors and less aggressive malignant tumors. Notwithstanding this, EES has been gradually adopted for squamous cell carcinoma (SCC), which is the most common histology among SN malignancies. However, an analysis of the outcomes of EES for patients with SCC is difficult because most articles included SCC a wide range of different tumor histologies. Therefore, we herein review and clarify the current status of EES focusing on SCC from an oncological perspective. The oncologic outcomes and the ability to achieve a histologically complete resection are similar between endoscopic and open approaches in highly selected patients with SN-SCC. Surgical complications associated with EES are likely similar for SN-SCC compared to other sinonasal malignancies. The indications for a minimally invasive approach such as EES in the management of patients with SN-SCC should be stricter than those for less aggressive malignant tumors because of the aggressive nature of SCC. Also, it is important to achieve negative surgical margins with EES in patients with SCC. We believe that the indications for EES for SN-SCC are widening due to advances in diagnostic imaging, and endoscopic surgical techniques and technologies. However, while expanding the indications for EES for SN-SCC we must carefully confirm that the outcomes support this strategy.

Novel Biomarkers in Sinonasal Cancers: from Bench to Bedside.

PURPOSE OF REVIEW: Sinonasal cancers are a heterogenous group of rare cancers for which histopathological diagnosis can be very challenging and treatment options are limited for advanced disease in particular. Here, we review the candidacy of novel diagnostic and prognostic biomarkers, and therapeutic targets for sinonasal cancers. RECENT FINDINGS: Molecular multidimensional analyses of sinonasal cancers have been lagging behind other major cancers, but there are numerous publications describing the discovery of novel candidate biomarkers, e.g. the methylation classifier, originally developed for brain cancers, and gene expression panels for the prediction of response to induction chemotherapy in sinonasal undifferentiated carcinoma. The most promising biomarkers are summarized and discussed further with regard to their clinical applicability and future potential. Many of the described novel biomarkers for sinonasal cancers will eventually overcome the pitfalls associated with the frequently non-specific immunohistological tests. With comprehensive, multidimensional molecular testing of these tumours in collaborative consortia projects, our better understanding of the molecular mechanisms of sinonasal cancers and their carcinogenesis will determine the most useful diagnostic and prognostic biomarkers, allow stringent multi-institutional validation and guide trials on targeted therapies.

Sinonasal Malignant Melanoma.

Sinonasal malignant mucosal melanoma (SNMM) is a rare, aggressive, and capricious tumour accounting for 4% of sinonasal malignancies. Recent studies suggest an increasing frequency. There are few large published series, but all authors report poor outcomes irrespective of treatment of approximately 25% 5-year survival. As a consequence, the American Joint Committee on Cancer (AJCC) have restaged all SNMMs as T3 or greater, irrespective of extent. Surgery remains the principle treatment modality. Survival and recurrence data analysis from a single-centre prospective cohort of 125 cases (all treated surgically with or without radiotherapy) showed 5-year overall survival was 28% and disease-free survival was 23.7%. Local control was achieved for a median of 21 months, with a 5-year disease control rate of 27.7%. However, endoscopically resected cases showed a significant overall survival advantage up to 5 years, confirming that endoscopic resection of SNMM does not adversely affect outcome and may even be beneficial up to 5 years. These findings are supported by other recent series in the literature. Radiotherapy did not improve local control or survival in this study, though there is debate in the literature as to its value. Cervical metastases confer a dramatically worse outcome. Chemotherapy has not previously shown much advantage, but more recently immunologic manipulation with drugs such as ipilimumab have shown promise. Thus far, the mutation status does not appear to affect survival outcomes, but NRAS mutations are relatively frequent and could be targeted in this disease by MEK inhibitors in the future.

Loss of smell and taste: a new marker of COVID-19? Tracking reduced sense of smell during the coronavirus pandemic using search trends.

OBJECTIVES: It has been demonstrated that reduction in smell and/or taste is the most predictive symptom in SARS-CoV-2/Covid-19 infection. We used Google Trends to analyze regional searches relating to loss of smell and taste across Italy, Spain, France, Brazil, and the United States of America and determined the association with reported Covid-19 cases. METHODS: In order to retrieve the data, we built a Python software program that provides access to Google Trends data via an application program interface. Daily COVID-19 case data for subregions of the five countries selected were retrieved from respective national health authorities. We sought to assess the association between raw search interest data and COVID-19 new daily cases per million for all regions individually. RESULTS: In total, we yielded 2188 sets of Google Trends data which included 548 time series of 4 anosmia and ageusia search concepts over the study period for 137 regions. These data indicated that differences in search interest for terms relating to anosmia and ageusia, between regions, is associated with geographical trends in new Covid-19 cases. CONCLUSIONS: We feel that Google search trends relating to loss of smell can be utilized to identify potential Covid-19 outbreaks on a national and regional basis.

Sinonasal Undifferentiated Carcinoma (SNUC): From an Entity to Morphologic Pattern and Back Again-A Historical Perspective.

Since the first description of sinonasal undifferentiated carcinoma (SNUC) as a distinctive highly aggressive sinonasal neoplasm with probable origin from the sinonasal mucosa (Schneiderian epithelium), SNUC has been the subject of ongoing study and controversy. In particular, the SNUC category gradually became a "wastebasket" for any undifferentiated or unclassifiable sinonasal malignancy of definite or probable epithelial origin. However, with the availability of more specific and sensitive immunohistochemical antibodies and increasing implementation of novel genetic tools, the historical SNUC category became the subject of progressive subdivision leading to recognition of specific genetically defined, reproducible subtypes. These recently recognized entities are characterized by distinctive genetic aberrations including NUTM1-rearranged carcinoma (NUT carcinoma) and carcinomas associated with inactivation of different members of the SWI/SNF chromatin-remodeling gene complex such as SMARCB1-deficient and less frequently SMARCA4-deficient carcinoma. The ring became almost closed, with recent studies highlighting frequent oncogenic IDH2 mutations in the vast majority of histologically defined SNUCs, with a frequency of 82%. A review of these cases suggests the possibility that "true SNUC" probably represents a distinctive neoplastic disease entity, morphologically, phenotypically, and genetically. This review addresses this topic from a historical perspective, with a focus on recently recognized genetically defined subsets within the SNUC spectrum.

ICAR: endoscopic skull-base surgery.

BACKGROUND: Endoscopic skull-base surgery (ESBS) is employed in the management of diverse skull-base pathologies. Paralleling the increased utilization of ESBS, the literature in this field has expanded rapidly. However, the rarity of these diseases, the inherent challenges of surgical studies, and the continued learning curve in ESBS have resulted in significant variability in the quality of the literature. To consolidate and critically appraise the available literature, experts in skull-base surgery have produced the International Consensus Statement on Endoscopic Skull-Base Surgery (ICAR:ESBS). METHODS: Using previously described methodology, topics spanning the breadth of ESBS were identified and assigned a literature review, evidence-based review or evidence-based review with recommendations format. Subsequently, each topic was written and then reviewed by skull-base surgeons in both neurosurgery and otolaryngology. Following this iterative review process, the ICAR:ESBS document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:ESBS document addresses the role of ESBS in primary cerebrospinal fluid (CSF) rhinorrhea, intradural tumors, benign skull-base and orbital pathology, sinonasal malignancies, and clival lesions. Additionally, specific challenges in ESBS including endoscopic reconstruction and complication management were evaluated. CONCLUSION: A critical review of the literature in ESBS demonstrates at least the equivalency of ESBS with alternative approaches in pathologies such as CSF rhinorrhea and pituitary adenoma as well as improved reconstructive techniques in reducing CSF leaks. Evidence-based recommendations are limited in other pathologies and these significant knowledge gaps call upon the skull-base community to embrace these opportunities and collaboratively address these shortcomings.

Peak nasal inspiratory flow measurement and visual analogue scale in a large adult population.

OBJECTIVES: Nasal obstruction is the most common symptom in nasal diseases. It can be evaluated objectively, that is by means of peak nasal inspiratory flow (PNIF) measures and/or subjectively by means of validated questionnaires. However, it has been reported that there is a lack of reliable correlation between subjective and objective measurements of nasal obstruction. The aim of the present study was to evaluate the correlation between PNIF measurements and the subjective sensation of nasal obstruction measured by means of a visual analogue scale (VAS) in a large population of consecutive rhinologic patients. DESIGN: Prospective clinical study. SETTING: Tertiary rhinological referral centre. PARTICIPANT MAIN OUTCOME MEASURES: A total of 641 consecutive subjects were enrolled. Visual analogue scale and PNIF were performed to assess nasal obstruction. Nasal septal deviation was classified according to Mladina classification, and its severity was assessed using three levels of severity. RESULTS: Although weak, there was a significant negative correlation (r = -0.13, P = 0.001) between PNIF and VAS. Dividing the population in those affected by nasal septal deviation (NSD) and those affected by chronic rhinosinusitis (CRS), a week negative correlation between PNIF and VAS was again confirmed in both groups (r = -0.208, P = 0.006 for NSD and r = -0.13, P = 0.04 for CRS). Peak nasal inspiratory flow and VAS were also evaluated according to the grade of polyps and the type and level of septal deviation. CONCLUSIONS: Visual analogue scale and PNIF significantly correlated, although with a low degree, in a large population of rhinologic patients. Peak nasal inspiratory flow, being cheap and simple to use, could be a good candidate to assist clinicians dealing with "airway" diseases in their daily clinical practice in order to provide comprehensive information on nasal function. Peak nasal inspiratory flow can in fact give some important rough insights on VAS, but these measurements cannot be alternative to each other.