Publications by authors named "Valerie J Lund"

93 Publications

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

Clin Transl Allergy 2021 Mar;11(1):e12002

Department of Respiratory Medicine, University College London Hospital NHS Foundation Trust, London, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clt2.12002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099201PMC
March 2021

Risk factors and characteristics associated with persistent smell loss in coronavirus disease 2019 (COVID-19) patients.

Int Forum Allergy Rhinol 2021 08 17;11(8):1280-1282. Epub 2021 Apr 17.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California San Diego, San Diego, California, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251222PMC
August 2021

Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy.

Nat Commun 2021 01 5;12(1):117. Epub 2021 Jan 5.

Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck, Austria.

Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20308-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785735PMC
January 2021

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

Auris Nasus Larynx 2021 Feb 4;48(1):41-49. Epub 2020 Dec 4.

International Head and Neck Scientific Group, Padua, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2020.11.018DOI Listing
February 2021

Sinonasal Malignant Melanoma.

Authors:
Valerie J Lund

Adv Otorhinolaryngol 2020 30;84:185-196. Epub 2020 Jul 30.

Professor Emeritus in Rhinology, UCL, London UK & Honorary Consultant Rhinologist and Anterior Skull Base Surgeon, Royal National Throat, Nose and Ear Hospital, UCLH, London, United Kingdom,

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000457937DOI Listing
June 2021

Novel Biomarkers in Sinonasal Cancers: from Bench to Bedside.

Curr Oncol Rep 2020 07 29;22(10):106. Epub 2020 Jul 29.

Royal National Throat, Nose and Ear Hospital/Head and Neck Centre, University College London Hospitals NHS Foundation Trust, London, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11912-020-00947-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387318PMC
July 2020

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

Expert Rev Anti Infect Ther 2020 11 16;18(11):1165-1170. Epub 2020 Jul 16.

Wigan and Leigh Teaching Hospitals NHS Foundation Trust , Wrightington, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14787210.2020.1792289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441792PMC
November 2020

Olfactory Loss of Function as a Possible Symptom of COVID-19.

JAMA Otolaryngol Head Neck Surg 2020 09;146(9):872-873

Royal National Throat, Nose and Ear Hospital, UCLH Foundation Trust, London, United Kingdom.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2020.1589DOI Listing
September 2020

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

Adv Anat Pathol 2020 Mar;27(2):51-60

International Head and Neck Scientific Group, Padua, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAP.0000000000000258DOI Listing
March 2020

ICAR: endoscopic skull-base surgery.

Int Forum Allergy Rhinol 2019 07;9(S3):S145-S365

University of Pennsylvania, Philadelphia, PA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22326DOI Listing
July 2019

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

Clin Otolaryngol 2019 07 21;44(4):541-548. Epub 2019 Apr 21.

Royal National Throat, Nose and Ear Hospital, University College London, London, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/coa.13329DOI Listing
July 2019

Betel nut chewing in high-income countries-lack of awareness and regulation.

Lancet Oncol 2019 02;20(2):181-183

Royal National Throat, Nose and Ear Hospital, University College London Hospitals NHS Trust, London, UK. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(18)30911-2DOI Listing
February 2019

Correction to: DNA methylation-based reclassification of olfactory neuroblastoma.

Acta Neuropathol 2018 09;136(3):505

In the original publication, the second name of the twentieth author was incorrect. It should read as 'Miguel Sáinz-Jaspeado'. The original publication of the article has been updated to reflect the change. This correction was authored by Ulrich Schüller on behalf of all authors of the original publication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00401-018-1887-yDOI Listing
September 2018

DNA methylation-based reclassification of olfactory neuroblastoma.

Acta Neuropathol 2018 08 5;136(2):255-271. Epub 2018 May 5.

Institute of Pathology, Julius-Maximilians-University, Würzburg, Germany.

Olfactory neuroblastoma/esthesioneuroblastoma (ONB) is an uncommon neuroectodermal neoplasm thought to arise from the olfactory epithelium. Little is known about its molecular pathogenesis. For this study, a retrospective cohort of n = 66 tumor samples with the institutional diagnosis of ONB was analyzed by immunohistochemistry, genome-wide DNA methylation profiling, copy number analysis, and in a subset, next-generation panel sequencing of 560 tumor-associated genes. DNA methylation profiles were compared to those of relevant differential diagnoses of ONB. Unsupervised hierarchical clustering analysis of DNA methylation data revealed four subgroups among institutionally diagnosed ONB. The largest group (n = 42, 64%, Core ONB) presented with classical ONB histology and no overlap with other classes upon methylation profiling-based t-distributed stochastic neighbor embedding (t-SNE) analysis. A second DNA methylation group (n = 7, 11%) with CpG island methylator phenotype (CIMP) consisted of cases with strong expression of cytokeratin, no or scarce chromogranin A expression and IDH2 hotspot mutation in all cases. T-SNE analysis clustered these cases together with sinonasal carcinoma with IDH2 mutation. Four cases (6%) formed a small group characterized by an overall high level of DNA methylation, but without CIMP. The fourth group consisted of 13 cases that had heterogeneous DNA methylation profiles and strong cytokeratin expression in most cases. In t-SNE analysis, these cases mostly grouped among sinonasal adenocarcinoma, squamous cell carcinoma, and undifferentiated carcinoma. Copy number analysis indicated highly recurrent chromosomal changes among Core ONB with a high frequency of combined loss of chromosome 1-4, 8-10, and 12. NGS sequencing did not reveal highly recurrent mutations in ONB, with the only recurrently mutated genes being TP53 and DNMT3A. In conclusion, we demonstrate that institutionally diagnosed ONB are a heterogeneous group of tumors. Expression of cytokeratin, chromogranin A, the mutational status of IDH2 as well as DNA methylation patterns may greatly aid in the precise classification of ONB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00401-018-1854-7DOI Listing
August 2018

Otorhinolaryngology and Diving-Part 2: Otorhinolaryngological Fitness for Compressed Gas Scuba Diving: A Review.

JAMA Otolaryngol Head Neck Surg 2018 Mar;144(3):259-263

Royal National Throat, Nose and Ear Hospital, University College London Hospitals NHS Trust, London, England.

Importance: Self-contained underwater breathing apparatus (scuba) diving has become increasingly popular with millions of people diving each year. Otorhinolaryngologists are often consulted either by patients or diving physicians regarding fitness to dive, and at present, the guidelines do not provide comprehensive information regarding the evaluation of this patient cohort. The aim of this review is to provide a comprehensive overview of existing otorhinolaryngological guidelines for fitness to dive recreationally.

Observations: There is a paucity of guidelines for assessing otorhinolaryngological fitness to dive in the recreational diver. Comprehensive guidelines exist from US, European, and UK regulatory bodies regarding fitness for commercial diving; however, not all of these can be directly extrapolated to the recreational diver. There are also a variety of conditions that are not covered either by the existing fitness for recreational diving guidelines or the commercial regulatory bodies.

Conclusions And Relevance: With the paucity of recreational fitness to dive guidelines we must draw on information from the commercial diving regulatory bodies. We have provided our own recommendations on the conditions that are not covered by either of the above, to provide otorhinolaryngologists with the information they require to assess fitness for recreational diving.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2017.2616DOI Listing
March 2018

Otorhinolaryngology and Diving-Part 1: Otorhinolaryngological Hazards Related to Compressed Gas Scuba Diving: A Review.

JAMA Otolaryngol Head Neck Surg 2018 Mar;144(3):252-258

Royal National Throat, Nose and Ear Hospital, University College London Hospitals NHS Trust, London, England.

Importance: Scuba diving is becoming increasingly popular. However, scuba diving is associated with specific risks; 80% of adults and 85% of juvenile divers (aged 6-17 years) have been reputed to have an ear, nose, or throat complaint related to diving at some point during their diving career. Divers frequently seek advice from primary care physicians, diving physicians, and otorhinolaryngologists, not only in the acute setting, but also related to the long-term effects of diving.

Observations: The principles underpinning diving-related injuries that may present to the otorhinolaryngologist rely on gas volume and gas saturation laws, and the prevention of these injuries requires both that the diver is skilled and that their anatomy allows for pressure equalization between the various anatomical compartments. The overlapping symptoms of middle ear barotrauma, inner ear barotrauma, and inner ear decompression sickness can cause a diagnostic conundrum, and a thorough history of both the diver's symptoms and the dive itself are required to elucidate the diagnosis. Correct diagnosis and appropriate treatment result in a more timely return to safe diving.

Conclusions And Relevance: The aim of this review is to provide a comprehensive overview of otorhinolaryngological complications during diving. With the increasing popularity of diving and the frequency of ear, nose, or throat-related injuries, it could be expected that these injuries will become more common and this review provides a resource for otorhinolaryngologists to diagnose and treat these conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2017.2617DOI Listing
March 2018

Head and Neck Cancer: A Review of the Impact of Treatment Delay on Outcome.

Adv Ther 2018 02 2;35(2):153-160. Epub 2018 Feb 2.

Coordinator of the International Head and Neck Scientific Group, Padua, Italy.

Delay between the initial symptoms, diagnosis, and the definitive treatment of head and neck cancers is associated with tumor progression and upstaging. These delays may lead to poor outcomes and may mandate more aggressive treatments with unnecessary morbidity and even mortality. The multidisciplinary team approach for the treatment of patients with head and neck cancers has improved organization of standard clinical guidelines, but this development has yet to translate into a demonstrable impact on survival. We review the association between waiting times (time between diagnosis and initiation of treatment) and clinical outcomes in patients with head and neck squamous cell carcinoma (HNSCC).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12325-018-0663-7DOI Listing
February 2018

The Impact of Histologic Phenotype in the Treatment of Sinonasal Cancer.

Adv Ther 2017 10 4;34(10):2181-2198. Epub 2017 Sep 4.

Coordinator of the International Head and Neck Scientific Group, Padua, Italy.

The management of sinonasal cancer is a challenge due to its low occurrence and anatomical and significant diversity of histological types. The therapeutic modality used should be tailored individually according to the histology, tumour stage, molecular profile and previous treatments. The clinical management of sinonasal cancer has improved greatly owing to developments in endoscopic surgery and precision radiotherapy. Complete surgical resection is the mainstay of sinonasal malignancies' management but multimodality therapy is associated with improved outcomes in certain histologies. The recognition of various histological types with biological behaviours more suitable for non-surgical modalities has allowed treatment protocols to become more tailored to the disease. In this review we aim to describe and to summarise the current data guiding the management of sinonasal cancer with emphasis on phenotypic variation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12325-017-0605-9DOI Listing
October 2017

Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial.

J Allergy Clin Immunol 2017 Oct 4;140(4):1024-1031.e14. Epub 2017 Jul 4.

Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands.

Background: Patients with eosinophilic nasal polyposis frequently require surgery, and recurrence rates are high.

Objective: We sought to assess the efficacy and safety of mepolizumab versus placebo for severe bilateral nasal polyposis.

Methods: This randomized, double-blind, placebo-controlled trial recruited patients aged 18 to 70 years with recurrent nasal polyposis requiring surgery. Patients received 750 mg of intravenous mepolizumab or placebo every 4 weeks for a total of 6 doses in addition to daily topical corticosteroid treatment. The primary end point was the number of patients no longer requiring surgery at Week 25 based on a composite end point of endoscopic nasal polyp score and nasal polyposis severity visual analog scale (VAS) score. Secondary end points included change in nasal polyposis severity VAS score, endoscopic nasal polyp score, improvement in individual VAS symptoms (rhinorrhea, mucus in throat, nasal blockage, and sense of smell), patient-reported outcomes, and safety.

Results: One hundred five patients received mepolizumab (n = 54) or placebo (n = 51). A significantly greater proportion of patients in the mepolizumab group compared with the placebo group no longer required surgery at Week 25 (16 [30%] vs 5 [10%], respectively; P = .006). There was a significant improvement in nasal polyposis severity VAS score, endoscopic nasal polyp score, all individual VAS symptom scores, and Sino-Nasal Outcome Test patient-reported outcome score in the mepolizumab compared with placebo groups. Mepolizumab's safety profile was comparable with that of placebo.

Conclusion: In patients with recurrent nasal polyposis receiving topical corticosteroids who required surgery, mepolizumab treatment led to a greater reduction in the need for surgery and a greater improvement in symptoms than placebo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2017.05.044DOI Listing
October 2017

The Role of Macrolides in Chronic Rhinosinusitis (CRSsNP and CRSwNP).

Curr Allergy Asthma Rep 2017 May;17(5):30

Royal National Throat, Nose and Ear Hospital, London, UK.

Purpose Of Review: We assess the literature on the pharmacokinetics, indications, important considerations, and effectiveness of long-term, low-dose macrolide antibiotics in chronic rhinosinusitis (CRS).

Recent Findings: The key to effective implementation of macrolide therapy in CRS is appropriate patient selection. Macrolides have demonstrated the most benefit in Th1-mediated non-eosinophilic CRS when used for durations of at least 3 months. Macrolide antibiotics have demonstrated great benefit when used for their anti-inflammatory or immunomodulatory properties, which include the blockage of pro-inflammatory cytokines, such as interleukin (IL)-8 and tumor necrosis factor-α (TNF-α). They have been used in CRS patients not responding to traditional corticosteroid-based treatment regimens, but appear to be most effective specifically in Th1-mediated non-eosinophilic CRS in long durations and low doses. Further research is needed to better identify characteristics known to correlate with macrolide response so early directed therapy can be implemented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11882-017-0696-zDOI Listing
May 2017

Nasal juvenile angiofibroma: Current perspectives with emphasis on management.

Head Neck 2017 05 15;39(5):1033-1045. Epub 2017 Feb 15.

Coordinator of the International Head and Neck Scientific Group.

Juvenile angiofibroma is an uncommon, benign, locally aggressive vascular tumor. It is found almost exclusively in young men. Common presenting symptoms include nasal obstruction and epistaxis. More advanced tumors may present with facial swelling and visual or neurological disturbances. The evaluation of patients with juvenile angiofibroma relies on diagnostic imaging. Preoperative biopsy is not recommended. The mainstay of treatment is resection combined with preoperative embolization. Endoscopic surgery is the approach of choice in early stages, whereas, in advanced stages, open or endoscopic approaches are feasible in expert hands. Postoperative radiotherapy (RT) or stereotactic radiosurgery seem valuable in long-term control of juvenile angiofibroma, particularly those that extend to anatomically critical areas unsuitable for complete resection. Chemotherapy and hormone therapy are ineffective. The purpose of the present review was to update current aspects of knowledge related to this rare and challenging disease. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1033-1045, 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24696DOI Listing
May 2017

Removing the Taboo on the Surgical Violation (Cut-Through) of Cancer.

JAMA Otolaryngol Head Neck Surg 2016 10;142(10):1010-1013

Coordinator of the International Head and Neck Scientific Group.

Importance: The surgical dictum of en bloc resection without violating cancer tissue has been challenged by novel treatments in head and neck cancer.

Observations: An analysis of treatment outcomes involving piecemeal removal of sinonasal, laryngeal, oropharyngeal, and hypopharyngeal cancer shows that it did not compromise tumor control. The rationale for the evolution toward use of this technique is outlined.

Conclusions And Relevance: While complete resection with clear margins remains a key end point in surgical oncology, we believe it is time to acknowledge that this time-honored dictum of avoiding tumor violation is no longer valid in selected situations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2016.1826DOI Listing
October 2016

Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps.

J Allergy Clin Immunol 2017 Apr 19;139(4):1195-1204.e11. Epub 2016 Sep 19.

Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom; MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, Guy's Campus, London, United Kingdom. Electronic address:

Background: Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs.

Objectives: We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions.

Methods: Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with "matched" heavy and light chains were cloned as IgG, and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays.

Results: Thirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE.

Conclusions: SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgGs can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as "superantibodies" through CDRs and framework regions to SEEs in SEE-anti-SEE IgE-FcεRI complexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2016.06.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380656PMC
April 2017

A novel insight into the immunologic basis of chronic granulomatous invasive fungal rhinosinusitis.

Allergy Rhinol (Providence) 2016 Jan;7(2):102-6

Department of Immunology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.

Background: Chronic granulomatous invasive fungal rhinosinusitis (CGIFRS) is a rare disease. The underlying immune responses that drive the development of CGIFRS, as opposed to successful pathogen clearance and controlled inflammation, are not currently known.

Objective: To characterize the immune responses associated with CGIFRS.

Methods: In addition to a battery of basic investigations, more in-depth immunologic testing involves ex vivo whole-blood stimulation with the polyclonal T-cell mitogen phytohemagglutinin and fungal antigens with interleukin (IL) 12, was undertaken to investigate cell-mediated immune responses associated with CGIFRS.

Results: Ex vivo whole-blood stimulation with the polyclonal T-cell mitogen phytohemagglutinin and fungal antigens with IL-12 identified reduced interferon gamma and increased IL-17A levels within the supernatant, which indicated increased in vivo T-helper (Th)17 responses and impaired Th1 responses compared with healthy controls.

Conclusion: These findings suggest that the development of CGIFRS may be associated with an abnormally exaggerated host Th17 response, which caused failure to clear the fungal pathogen with refractory fungal infection of mucosal membranes, resulting in chronic tissue inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2500/ar.2016.7.0162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010430PMC
January 2016

Safety of human olfactory mucosal biopsy for the purpose of olfactory ensheathing cell harvest and nerve repair: a prospective controlled study in patients undergoing endoscopic sinus surgery.

Rhinology 2016 06;54(2):183-91

Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.

Background: Nasal olfactory mucosa is an accessible source of olfactory ensheathing cells for spinal cord regeneration. However, safety of the biopsy technique and the effects on sense of smell and nasal function have not been robustly assessed in the form of a prospective controlled study.

Methodology: National Health Service ethical approval was granted for this study of 131 patients. The primary outcome measure was olfactory function and the secondary outcomes included postoperative complication rates as well as the SNOT 22, NOSE scale scores and surgeon reported (Lund-Kennedy score) nasal function outcomes.

Results: 65 patients underwent functional endoscopic sinus surgery (FESS) and superior turbinate biopsy, and 66 patients underwent FESS only as the control group. There was no significant difference in complication rates between the two groups. All Olfactory function outcomes were unaffected following olfactory biopsy. We demonstrated that the patients quality of life and nasal patency as well as surgeon reported outcome measurements remain unaffected following olfactory harvesting.

Conclusions: We have uniquely provided level 2a evidence for the safety of endoscopic biopsy of olfactory mucosa, which does not affect nasal function or the sense of smell compared to standard FESS without biopsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4193/Rhino15.365DOI Listing
June 2016

Management of rhinosinusitis during pregnancy: systematic review and expert panel recommendations.

Rhinology 2016 06;54(2):99-104

Royal National Throat, Nose and Ear Hospital, University College London Hospitals, London, United Kingdom.

Background: Management of rhinosinusitis during pregnancy requires special considerations.

Objectives: 1. Conduct a systematic literature review for acute and chronic rhinosinusitis (CRS) management during pregnancy. 2. Make evidence-based recommendations.

Methods: The systematic review was conducted using MEDLINE and EMBASE databases and relevant search terms. Title, abstract and full manuscript review were conducted by two authors independently. A multispecialty panel with expertise in management of Rhinological disorders, Allergy-Immunology, and Obstetrics-Gynecology was invited to review the systematic review. Recommendations were sought on use of following for CRS management during pregnancy: oral corticosteroids; antibiotics; leukotrienes; topical corticosteroid spray/irrigations/drops; aspirin desensitization; elective surgery for CRS with polyps prior to planned pregnancy; vaginal birth versus planned Caesarian for skull base erosions/ prior CSF rhinorrhea.

Results: Eighty-eight manuscripts underwent full review after screening 3052 abstracts. No relevant level 1, 2, or 3 studies were found. Expert panel recommendations for rhinosinusitis management during pregnancy included continuing nasal corticosteroid sprays for CRS maintenance, using pregnancy-safe antibiotics for acute rhinosinusitis and CRS exacerbations, and discontinuing aspirin desensitization for aspirin exacerbated respiratory disease. The manuscript presents detailed recommendations.

Conclusions: The lack of evidence pertinent to managing rhinosinusitis during pregnancy warrants future trials. Expert recommendations constitute the current best available evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4193/Rhino15.228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797655PMC
June 2016

Peak nasal inspiratory flow and peak expiratory flow. Upright and sitting values in an adult population.

Rhinology 2016 06;54(2):160-3

Ear Institute, University College London, London, United Kingdom.

Background: Nasal obstruction is correlated with a decreased quality of life . An easy way to evaluate nasal patency is the peak nasal inspiratory flow (PNIF) measurement. Normal PNIF values have been published by many authors. However, some authors evaluated volunteers in a sitting position, while others have measured PNIF values in standing volunteers. Body position has been shown to influence pulmonary function, with differences between sitting and upright positions. As nasal and pulmonary flows are strictly related, the present pilot study tried to establish whether PNIF/PEF changed with body position in adults.

Methodology: PNIF and PEF were measured in sitting and standing positions with the order of testing randomized in 76 healthy volunteers, 30 male (40 ± 16 years).

Results: In the group as a whole between sitting and upright position, PEF was significantly different (p=0.009), while PNIF showed a trend towards a significant difference (p=0.10).

Conclusions: The present study, although showing a generally positive effect of the standing position on PEF values, does not show a clear effect on PNIF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4193/Rhino15.180DOI Listing
June 2016
-->