Medikamentöse Therapie neuroendokriner Neoplasien des Gastrointestinaltrakts

Zusammenfassung

Hintergrund

Neuroendokrine Neoplasien (NEN) des Verdauungstrakts stellen eine seltene und heterogene Gruppe von Tumorerkrankungen dar. Dies erschwert die Vorgabe einheitlicher Therapieschemata.

Ziel

Die aktuelle Datenlage zur medikamentösen Therapie gastrointestinaler NEN soll dargestellt werden.

Methoden

Diskussion publizierter Studien und Expertenempfehlungen zur medikamentösen Therapie von gastroenteropankreatischen neuroendokrinen Neoplasien (GEP-NEN)

Ergebnisse

Wichtigstes therapeutisches Prinzip ist die komplette chirurgische Tumorentfernung. Ist diese nicht möglich, erfolgt die Therapie in der Regel multimodal und multidisziplinär und orientiert sich an der Tumorentität, dem individuellen Spontanverlauf sowie der Beschwerdesymptomatik. Bei Vorliegen eines spezifischen klinischen Hormonsyndroms sind langwirksame Somatostatinanaloga (SSA) die Therapie der Wahl. Sie stellen auch die Grundlage der antiproliferativen Therapie gut differenzierter gastroenteropankreatischer neuroendokriner Tumoren (GEP-NET) dar. Bei ausreichender Somatostatinrezeptor-Expression des Tumors steht als systemische Therapieoption die Peptidradiorezeptortherapie (PRRT) zur Verfügung. Bei gering differenzierten neuroendokrinen Karzinomen und NET des Pankreas stellen Platin- bzw. Streptozotocin-basierte Chemotherapien eine wichtige Therapieoption dar. Der Multityrosinkinaseinhibitor Sunitinib und der mTOR-Inhibitor Everolimus sind für die Behandlung pankreatischer NET zugelassen, Everolimus zudem auch für gastrointestinale NEN.

Schlussfolgerungen

Zur Behandlung von GEP-NEN stehen eine Reihe effektiver therapeutischer Optionen zur Verfügung. Die Entscheidung für ein Therapiekonzept sollte individuell im Rahmen eines in der Behandlung dieser Tumoren erfahrenen interdisziplinären Tumorboards festgelegt werden.

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Primary cutaneous mucoepidermal carcinoma

Mucoepidermal carcinoma (MEC) is a tumour having mixed components of mucus secreting and epidermoid cells. Salivary glands are the the most common site of origin. Primary cutaneous MEC is a rare presentation. We report a primary cutaneous MEC in a 98-year-old woman presenting a noduloulcerative lesion over the dorsum of the nose. Histopathology of the tumour showed nests of epidermoid cells with glandular differentiation and mucin production. The diagnosis was confirmed by immunohistochemistry.

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Systemic thrombolysis in a patient with massive pulmonary embolism and recent glioblastoma multiforme resection

While trials of systemic thrombolysis for submassive and massive pulmonary embolism (PE) report intracranial haemorrhage (ICH) rates of 2%–3%, the risk of ICH in patients with recent brain surgery or intracranial neoplasm is unknown since these patients were excluded from these trials. We report a case of massive PE treated with systemic thrombolysis in a patient with recent neurosurgery for an intracranial neoplasm. We discuss the risks and benefits of systemic thrombolysis for massive PE in the context of previous case reports, prior cohort studies and trials, and current guidelines. There may be times when the immediate risk of death from massive PE outweighs the risk of ICH from systemic thrombolysis, even when guideline-listed major contraindications exist. This case provides an example of how the haemodynamic benefit of systemic thrombolysis outweighed the impact of ICH in a patient who had undergone recent neurosurgical resection of a glioblastoma multiforme tumour.

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Lyric hearing aid: a rare cause of benign necrotising otitis externa/external ear canal cholesteatoma

An 80-year-old Caucasian man presented with an incidental and asymptomatic lesion in his right ear thought to be secondary to his use of hearing aids for presbycusis. He used Lyric hearing aids, designed for 24 hours-a-day use for 4 months at a time and had no other previous otological problems. He underwent a bony meatoplasty and vascular flap reconstruction via a retroauricular approach to remove the lesion for histological analysis and regrafting of the area. The lesion was confirmed on histopathology as an ear canal cholesteatoma.

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Follicular bronchiolitis in an HIV-infected individual on combination antiretroviral therapy with low CD4+ cell count but sustained viral suppression

A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis and was treated with prednisolone. Despite complete viral suppression and increasing CD4+ count (162 cells/µL), he was readmitted with PCP in April 2015. Subsequently, he returned to Denmark (CD4+ count: 80 cells/µL, viral suppression). Over the following months, he developed progressive dyspnoea. Lung function tests demonstrated severely reduced lung capacity with an obstructive pattern and a moderately reduced diffusion capacity. High resolution computer tomography revealed minor areas with tree-in-bud pattern and no signs of air trapping on expiratory views. Lung biopsy showed lymphocytic infiltration surrounding the bronchioles with sparing of the alveolar septa. He was diagnosed with follicular bronchiolitis. The patient spontaneously recovered along with an improvement of the immune system.

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Randomized Split-face, Controlled Comparison of Treatment with 1565 nm Non-ablative Fractional Laser for Enlarged Facial Pores

Abstract

Enlarged pores are common cosmetic concerns¹. Though non-ablative fractional lasers (NAFLs) have been used reducing enlarged facial pores, a prospective, split-face, controlled study with objective assessment is still in blank. 1,565 nm NAFL (M22 ^™ ResurFX^™, Lumenis^® Ltd, Yokneam, Israel), proved effective on skin elasticity and stretch marks², was further aimed to assess for its safety and efficacy on enlarged facial pores.

This article is protected by copyright. All rights reserved.

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The extent of surgery for benign parotid pathology and its influence on complications: A prospective cohort analysis

Publication date: Available online 29 November 2017
Source:American Journal of Otolaryngology
Author(s): Wai Keat Wong, Subhaschandra Shetty
BackgroundThe surgical management of benign parotid tumors is aimed at complete extirpation of the mass with preservation of facial nerve function. There is a relative paucity of literature pertaining to complications after benign parotid surgery and related risk factors. We aim to critically review the outcomes following treatment of benign parotid pathology when surgery entailed either complete superficial parotidectomy (CSP), partial superficial parotidectomy (PSP) or extracapsular dissection (ECD).Material and methodsThis is a review of prospectively collected data of all parotidectomies performed between June 2006 to June 2016 for histologically-proven benign pathology of the parotid. Median follow-up time was 31.6weeks.ResultsA total of 101 parotidectomies were carried out on 97 patients (40 CSP, 56 PSP and 5 ECD). Pleomorphic adenoma (48.4%) and Warthin tumors (32.7%) were the most common pathologies. Temporary facial weakness occurred after 7 operations (6.9%). Facial weakness was permanent in 4 cases (3.9%). The rates of sialocele and salivary fistula were 4.9% and 0.9%, respectively. Only one patient (0.9%) developed Frey Syndrome postoperatively. No significant associations between extent of parotid surgery and postoperative facial nerve dysfunction (p=0.674) or wound complications (p=0.433) were observed. Univariate analyses for potential contributing factors such as advanced age, smoking status, tumor location or histology did not demonstrate any increased risk with developing postoperative complications.ConclusionPartial superficial parotidectomy was associated with low rates of morbidity to the facial nerve and surgical wound. The results were comparable to complete superficial parotidectomy. We recommend offering patient partial superficial parotidectomy where appropriate and this is in line with the current trend of minimising surgical dissection, thereby potentially decreasing the risk of short-term and long-term complications.



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Acute Chest Syndrome: An Ongoing Challenge for Physicians Caring for Children with Sickle Cell Disease

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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Diet, Lung Function, and Asthma Exacerbations in Puerto Rican Children

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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Neutrophil–Lymphocyte Ratio in Children with Recurrent Wheezing

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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Developing a Mobile Health Intervention for Low-Income, Urban Caregivers of Children with Asthma: A Pilot Study

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC

Abstract

Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations affect comparable signaling pathways such as RB restriction of cell cycle progression or p53 inactivation. Despite its low incidence, MCC recently received much attention based on its exquisite immunogenicity and the resulting major success of immune modulating therapies. Here, we summarize current knowledge on epidemiology, biology and therapy of MCC as conclusion of the project 'Immune Modulating strategies for treatment of Merkel Cell Carcinoma', which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC.

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Making and working of a new electronic resource for patients, carers and professionals: maxfacts.uk

Many maxillofacial patients have serious short, medium, or long-term problems, as well as having to make informed decisions about often life-changing interventions. Validated comprehensive information, at the right time and the right level for a diverse group of users (patients, carers, and professionals), is vital if patients are to make a serious contribution to their treatment. We describe the development of an online resource for this purpose. Maxfacts.uk aims to cover every aspect of oral and maxillofacial surgery and care, from neck dissection and ballistic wounds to physiotherapy and texture-modified foods.

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Nodular fasciitis of the temporomandibular joint: a case report

Nodular fasciitis is a relatively rare benign lesion of the soft tissue, which often presents in the fascia or deep subcutaneous tissues. It most commonly presents in the upper extremities and trunk and the head and neck region, particularly in younger patients. Its pathogenesis is poorly understood and it is predominantly thought to be a reactive lesion, although some have suggested that it may be a benign neoplasm. Advances in molecular testing and imaging have greatly assisted diagnosis. We discuss the benefits of ubiquitin-specific protease 6 (USP6) gene rearrangement testing and magnetic resonance imaging (MRI) to aid this uncommon diagnosis.

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Prognosis of oral cancer: a comparison of the staging systems given in the 7th and 8th editions of the American Joint Committee on Cancer Staging Manual

The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual introduces "depth of invasion" and "extranodal extension" into the head and neck section, and our aim was to find out if these changes have an impact on prognosis. We evaluated 174 patients who had had oral squamous cell carcinomas (SCC) resected between 2003 and 2012. The clinical records were reviewed, the patients' tumours restaged according to the 8th edition of the AJCC, and we analysed five-year survival to verify whether different correlations were made between the T and N stages and disease-specific survival using the 7th and 8th editions.

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Is it better to bend wires occlusally or apically during placement of arch bars for intermaxillary fixation?

We evaluated 78 patients who had intermaxillary fixation (IMF) of fractured mandibular condyles with arch bars and wires. Depending on whether the wires were bent apically or occlusally during placement of the arch bars, we randomly divided the patients into two groups (n=39 in each), then compared pain, satisfaction with oral hygiene, and complications between the groups at five to six weeks postoperatively when the arch bars were removed. Outcomes were significantly better in the occlusal group than in the apical group.

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Retroseptal transconjunctival approach for fractures of the zygomaticomaxillary complex: a retrospective study

We designed a retrospective study to evaluate the efficacy of retroseptal transconjunctival approaches in the management of fractures of the zygomaticomaxillary complex (ZMC). The patients were from a single institution, and had had three-point fixation of fractures of the ZMC between 2008 and 2016. A total of 77 patients (56 men and 21 women with a mean (range) age of 28 (18–54) years), were divided into two groups. Group I (n=51) had had reduction and fixation of the infraorbital rim using a retroseptal transconjunctival approach.

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The extent of surgery for benign parotid pathology and its influence on complications: A prospective cohort analysis

The surgical management of benign parotid tumors is aimed at complete extirpation of the mass with preservation of facial nerve function. There is a relative paucity of literature pertaining to complications after benign parotid surgery and related risk factors. We aim to critically review the outcomes following treatment of benign parotid pathology when surgery entailed either complete superficial parotidectomy (CSP), partial superficial parotidectomy (PSP) or extracapsular dissection (ECD).

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Uterus transplantation: A Rapidly Expanding Field

No abstract available

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Oral cancer databases: a comprehensive review

Abstract

Cancer database is a systemic collection and analysis of information on various human cancers at genomic and molecular level that can be utilized to understand various steps in carcinogenesis and for therapeutic advancement in cancer field. Oral cancer is one of the leading causes of morbidity and mortality all over the world. The current research efforts in this field are aimed at cancer etiology and therapy. Advanced genomic technologies including microarrays, proteomics, transcrpitomics and gene sequencing development have culminated in generation of extensive data and subjection of several genes and microRNAs that are distinctively expressed and this information is stored in the form of various databases. Extensive data from various resources has brought the need for collaboration and data sharing in order to make effective use of this new knowledge. The current review provides comprehensive information of various publicly accessible databases that contain information pertinent to oral squamous cell carcinoma (OSCC) and databases designed exclusively for OSCC. The databases discussed in the present paper are Protein-Coding Gene Databases and microRNA Databases. This paper also describes gene overlap in various databases, which will help researchers to reduce redundancy and focus on only those genes, which are common to more than one databases. We hope such introduction will promote awareness and facilitate the usage of these resources in the cancer research community and researchers can explore the molecular mechanisms involved in the development of cancer, which can help in subsequent crafting of therapeutic strategies.

This article is protected by copyright. All rights reserved.

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Dermatologist Density and Volume and Costs of Dermatology Procedures

This cross-sectional study uses the 2013 Medicare Provider Utilization and Payment Database to characterize the effect of geographic variations in dermatologist density on the provision of dermatology procedures within Medicare.

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Topical Tacalcitol for a Family With Follicular Keratosis of the Chin

This case report describes the use of topical tacalcitol to treat follicular keratosis of the chin in 2 brothers.

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Laboratory Monitoring During Systemic Terbinafine Therapy for Pediatric Onychomycosis

This retrospective medical record review examines the prevalence of laboratory monitoring and laboratory abnormalities during systemic terbinafine therapy in pediatric onychomycosis.

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Allergen Concerns and Popular Skin Care Products

To the Editor We read with great interest the article by Xu et al published in a recent issue of JAMA Dermatology highlighting the high prevalence of contact allergens in common moisturizers. Their data mirror similar results in our recent study investigating contact allergens in pediatric personal care products marketed as hypoallergenic, dermatologist recommended and/or tested, fragrance free, or paraben free. Similar to the study by Xu et al, which found that 88% of common moisturizers contained at least 1 common contact allergen, we found that 167 of 187 of our selection of pediatric products (89%) contained at least 1 allergen.

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Allergen Concerns and Popular Skin Care Products

To the Editor We read with great interest the Original Investigation by Xu et al titled "Consumer Preferences, Product Characteristics, and Potentially Allergenic Ingredients in Best-Selling Moisturizers" and published in a recent issue of JAMA Dermatology. In discussions with dermatology colleagues regarding this article, we noticed another disturbing marketing trend: the labeling of skin care products marketed for babies.

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Allergen Concerns and Popular Skin Care Products—Reply

In Reply We thank Hamann and Thyssen, as well as Harview and Hsiao, for their interest in our work and thoughtful commentaries. We agree that the safety and affordability of cosmetics and personal care products explicitly marketed toward the pediatric population is important to public health. In a recent publication of all adverse events (AE) submitted to the US Food and Drug Administration surrounding cosmetics and personal care products from 2004 to 2016, baby products were associated with the highest percentage of self-reported serious AEs (eg, death, serious injury, or hospitalization).

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Preference-Based QOL Measures for Economic Evaluations in Early Melanoma

This study uses randomized clinical trial data to compare utility scores from the AQoL-8D and the FACT-M and evaluate the sensitivity of both instruments in identifying the influence of fear of cancer recurrence on health-related quality of life in patients with early-stage melanoma.

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Indoor allergen levels in settled airborne dust are higher in day-care centres than at home

Abstract

Background

Early life sensitization to indoor allergens predicts asthma development. Aim of study was to compare allergen concentrations in day-care centres (DCC) to those in private homes.

Methods

Settled airborne dust was collected four times a year from 20 German DCC (620 samples), and from the homes of children and day-care workers (602 samples) using electrostatic dust collectors (EDC). The samples were analysed with fluorescence-enzyme-immunoassays recognising domestic mite allergens (DM), Fel d 1, Can f 1 and Mus m 1. Pet allergen thresholds that discriminate samples from homes with cats or dogs to those without were calculated using receiver-operator characteristics. Influences on allergen levels were analysed using multilevel models.

Results

Allergen loads were on average higher in DCC than in homes. In DCC, 96% of the samples were positive for DM, 95% for Can f 1, 90% for Fel d 1, and 83% for Mus m 1. In homes, 84% contained DM, 48.5% Can f 1, 33% Fel d 1, and 43% Mus m 1. The threshold level for homes with dogs was 75 ng/m² Can f 1 (96.8% sensitivity, 96% specificity), and 46 ng/m² Fel d 1 for homes with cats (92% sensitivity, 94.9% specificity). In DCC, Can f 1 and Fel d 1 loads were higher than these thresholds in 37% and 54% of the samples, respectively. Allergen levels were significantly influenced by the season and room type; however, carpets on floors had no influence.

Conclusions

Mite, mouse, cat and dog allergens were mostly higher in DCC than in homes. Exposure to dog and cat allergens in DCC often reached levels of households with pets.

This article is protected by copyright. All rights reserved.

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Pregnancy and perinatal conditions and atopic disease prevalence in childhood and adulthood

Abstract

Background

Previous studies showed controversial results for the influence of pregnancy-related and perinatal factors on subsequent respiratory and atopic diseases in children. The aim of this study was to assess the association between perinatal variables and the prevalence of asthma, bronchial hyperreactivity, flexural eczema, allergic rhinitis, and sensitization in childhood and early adulthood.

Methods

The studied population was first examined in Munich and Dresden in 1995/1996 at age 9-11 yrs. Participants were followed until age 19-24 yrs. using questionnaires and clinical examinations. Associations between perinatal data and subsequent atopic diseases were examined using logistic regression analyses adjusting for potential confounders.

Results

Cesarean section was statistically significantly associated with BHR in early adulthood (Odds Ratio 4.8, 95% confidence interval 1.5-15.2), while assisted birth was associated with presence of asthma symptoms in childhood (2.2, 1.2-3.9), flexural eczema symptoms (2.2, 1.2-4.3) and doctor's diagnosis of atopic dermatitis (1.9, 1.0-3.4) in childhood, and sensitization in early adulthood (2.2, 1.1-4.3). Lower birth length (1.9, 1.1-3.2), lower birth weight (0.5, 0.3-0.9) and higher birth weight (0.6 (0.4-1.0)) were predictive of sensitization in early adulthood compared to average birth length and birth weight, respectively. None of the other perinatal factors showed statistically significant associations with the outcomes.

Conclusions

Our results indicate that children, who are born by Cesarean section and especially by assisted birth, might be at greater risk for developing asthma, flexural eczema and sensitization and should hence be monitored. Prenatal maternal stress might partly explain these associations, which should be further investigated.

This article is protected by copyright. All rights reserved.

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Asthma Screening in Pediatric Sickle Cell Disease: A Clinic-Based Program Using Questionnaires and Spirometry

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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A Biomarker-driven, Open Label, Single Arm, Multicentre Phase II Study of Abemaciclib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Who Failed to Platinum-based Therapy

Conditions:   HNSCC;   Head and Neck Neoplasms
Intervention:   Drug: Abemaciclib
Sponsor:   Seoul National University Hospital
Recruiting

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Evaluation of ABEMACICLIB Monotherapy in Patients With Locally Advanced/Metastatic Head and Neck Cancer After Failure of Platinum and Cetuximab or Anti-EGFR-based Therapy and Harboring an Homozygous Deletion of CDKN2A, and/or an Amplification of CCND1 and/or of CDK6

Conditions:   Head and Neck Cancer;   Advanced Cancer;   Metastatic Cancer
Intervention:   Drug: Abemaciclib
Sponsor:   Centre Leon Berard
Not yet recruiting

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Superiorly based facial artery musculomucosal flap: A versatile pedicled flap

Abstract

Background

The superiorly based facial artery musculomucosal (FAMM) flap is pedicled on the angular artery. This flap offers a well-vascularized mucosal surface allowing closure of medium size defects, most frequently within the oral cavity and intranasal region.

Methods

We describe a superiorly based harvest of the FAMM flap, which may be used for closure of multiple head and neck surgical defects. An operative technique video is provided, which can be viewed online.

Results

Our results demonstrate a fast and relatively straightforward harvest technique of the FAMM flap. This intraoral flap is a useful reconstructive tool, which also has the advantage to leave no visible external scars.

Conclusion

The superiorly pedicled FAMM flap is a versatile and effective technique that may be integrated in the algorithm for reconstruction of head and neck defects.

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IL-33 Expression in Chronic Rhinosinusitis with Nasal Polyps and Its Relationship with Clinical Severity

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by epithelial inflammation and tissue eosinophilic infiltration. Interleukin-33 (IL-33) is a key inflammatory cytokine that mediates eosinophilic infiltration. Objective: The aim of our study was to investigate the expression and role of IL-33 in eosinophilic CRS with nasal polyps (ECRSwNP) and in noneosinophilic CRS with nasal polyps (nECRSwNP), and to analyze their correlation with clinical severity. Methods: The study enrolled 25 patients with ECRSwNP, 27 patients with nECRSwNP, and 12 control subjects, based on immunohistochemical staining. Protein and mRNA expressions of IL-33 in sinus mucosal samples were determined by immunohistochemistry and real-time polymerase chain reaction. Sino-Nasal Outcome Test-20 (SNOT-20) score, visual analog scale (VAS) score, endoscopy score, and computed tomography (CT) score were assessed preoperatively. Results: IL-33 expression levels in the CRSwNP group were significantly higher than those in the control group (p p p p Conclusion: IL-33 expression plays an important role in patients with CRSwNP. No significant differences were observed between the ECRSwNP and nECRSwNP groups with respect to SNOT-20 score, VAS score, endoscopy score, or CT score. IL-33 expression was correlated with eosinophil counts and endoscopy score.
ORL 2017;79:323-330

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Cover Image

The cover image, by M. E. Lachowicz-Scroggins et al., is based on the Original Article Corticosteroid and long-acting ß-agonist therapy reduces epithelial goblet cell metaplasia, DOI: 10.1111/cea.13015.

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Issue Information

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Asthma, urticaria and less rare than expected FPIES

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Forthcoming Meetings

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Endoskopie und Bildgebung

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LASER Medicine treatments by Alexandros G. Sfakianakis, Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com Laser Facial Mole Removal Laser Face Dark Spot Removal Laser Tattoo Removal Laser Skin Spot Mole Removal Laser Wart Skin Tag Removal Laser Face Dark Spot Removal Laser Freckle Removal

​

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Serum autoantibodies against epithelial cell adhesion molecules as disease biomarkers of eosinophilic esophagitis

Abstract

Eosinophilic esophagitis is an allergic/immune-mediated disease where a Th2 response is triggered by food or environmental allergens.¹² The incidence and prevalence of EoE have been increasing over the past two decades.³ Because endoscopy and biopsy are required for diagnosis and monitoring, health care costs related to EoE are significant.

This article is protected by copyright. All rights reserved.

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Synergistic cytotoxicity of a prostate cancer-specific immunotoxin in combination with the BH3 mimetic ABT-737

Abstract

In many tumors, including prostate cancer, anti-apoptotic members of the Bcl-2 family are overexpressed and cause cell death resistance, which is a typical hallmark of cancer. Different therapeutic approaches, therefore, aim to restore the death mechanisms for enhanced apoptosis. Our recombinant immunotoxin D7(VL-VH)-PE40 is composed of the scFv D7(VL-VH) against the prostate-specific membrane antigen (PSMA) on the surface of prostate cancer cells and of the cytotoxic domain of the bacterial toxin Pseudomonas Exotoxin A (PE40). Since Pseudomonas Exotoxin A-based immunotoxins are known to preferentially inhibit the expression of the anti-apoptotic protein Mcl-1, the rationale was to test our immunotoxin in combination with the BH3 mimetic ABT-737, which specifically inhibits Bcl-2, Bcl-xl, and Bcl-w for enhanced induction of apoptosis in prostate cancer cells. The immunotoxin showed high and specific binding and cytotoxicity against PSMA expressing prostate cancer cells marked by a direct inhibition of Mcl-1. The combination of the immunotoxin with a subtoxic concentration of ABT-737 caused additive or even synergistic effects, which were based on an enhanced apoptosis induction as detected by poly(ADP-ribose) polymerase (PARP) and Caspase-3 cleavage in Western blot. Our study shows that the combination therapy of immunotoxin plus ABT-737 is a promising approach for the future treatment of advanced prostate cancer to improve therapeutic efficacy and to reduce adverse side effects.

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Intranasal immunization with phosphorylcholine suppresses allergic rhinitis in mice

Objectives/Hypothesis

Intranasal immunization with phosphorylcholine (PC) is known to reduce immunoglobulin (Ig)E production. However, its effects on the occurrence of allergic rhinitis (AR) are unknown. This study was performed to evaluate the effects of PC-keyhole limpet hemocyanin (PC-KLH) and to examine the effects on the occurrence of AR in a murine model of AR.

Study Design

In vivo study using an animal model.

Methods

Forty-five female BALB/c mice were divided into three groups; those pretreated with intranasal administration of PC-KLH followed by intraperitoneal sensitization and nasal challenge with ovalbumin (OVA) (group A), those untreated with PC-KLH followed by sensitization and nasal challenge with OVA (group B), and those untreated with PC-KLH or OVA as controls (group C). Nasal symptoms, allergic inflammation in the nasal mucosa, OVA specific IgE production, and cytokine profile were compared among those three groups. Dendritic cells (DCs) were isolated from splenic cells and PC-KLH–stimulated interleukin (IL)-12p40 production was measured.

Results

The mice pretreated with PC-KLH showed lower allergic nasal symptoms and inflammation compared to untreated mice. The levels of total IgE and OVA-specific IgE in serum, and IL-4 production by nasal and splenic CD4⁺ T cells were significantly reduced by PC-KLH pretreatment. Furthermore, IL-12p40 production by DCs was induced by PC-KLH in a dose-dependent manner.

Conclusions

Intranasal administration of PC-KLH suppressed allergic inflammation in nasal mucosa and antigen-specific IgE production by downregulating Th2-type immune response. Intranasal immunization with PC might be useful to prevent AR and upper airway bacterial infection.

Level of Evidence

NA Laryngoscope, 2017

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Treatment of tracheoesophageal fistula after laryngectomy by a customized tracheal prosthesis

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Tinnitus and its risk factors in african americans: The Jackson Heart Study

Objectives/Hypothesis

To describe the prevalence of reported tinnitus and tinnitus handicap in the all–African American Jackson Heart Study (JHS) cohort, with assessment of the relationship to cardiometabolic risk and depression.

Study Design

Prospective cohort study.

Methods

Audiologic data were obtained from a sample of 1,314 participants of the JHS. Reported tinnitus was assessed dichotomously (yes/no) by interview and with the Tinnitus Handicap Inventory (THI). The statistical relationship of reported tinnitus and tinnitus handicap to various cardiometabolic risks (i.e., hypertension and waist circumference) and Center for Epidemiologic Studies Depression scale (CES-D) was assessed with logistic and gamma regression procedures.

Results

Tinnitus was found to be a highly prevalent condition (29.5%), with an additionally high rate of individuals who report at least slight tinnitus handicap (35%). Hypertension (β = 1.344, 95% confidence interval [CI]: 1.015-1.780, P = .039) and waist circumference (β = 1.009, 95% CI: 1.001-1.018, P = .021) were found to have a statistically significant relationship with THI score, depending on the level of covariate adjustment. Depression, as measured by the CES-D, was found to have a statistically significant relationship with both reported tinnitus (odds ratio [OR]: 1.051, 95% CI: 1.030-1.072, P < .001) and THI score (β = 1.029, 95% CI: 1.013-1.047, P = .001), which persisted for all levels of covariate adjustment in statistical models.

Conclusions

Tinnitus was found to be highly prevalent in the JHS, and certain measures of cardiometabolic risk are weakly related to both reported tinnitus and level of tinnitus handicap. A consistent relationship between depression and tinnitus/level of tinnitus handicap was observed.

Level of Evidence

2b Laryngoscope, 2017

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Cytologic findings of spindle epithelial tumor with thymus-like elements

Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare and morphologically unique biphasic pediatric thyroid tumor of low malignant potential. There are less than 50 cases reported in the literature and few reported metastases. Despite the common usage of needle aspiration for thyroid and lymph node evaluation, cytologic descriptions of SETTLE are rare and tend to focus on a hypercellular biphasic appearance. We report aspirate findings of early cystic lymph node metastases in a 14-year-old girl, showing abundant matrix and low cellularity. We propose that the lack of recognition of this abundant matrix and cystic ultrasound appearance (as well as rarity of this tumor) may account for the low number of cytologic descriptions in the literature. Improved recognition may lead to increased usefulness of aspiration in the diagnosis and follow-up of SETTLE. Laryngoscope, 2017

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Correlations between cystic fibrosis genotype and sinus disease severity in chronic rhinosinusitis

Objective

Cystic fibrosis (CF) patients commonly develop chronic rhinosinusitis (CRS). The impact of the most common cystic fibrosis transmembrane conductance regulator (CFTR) mutation, F508del, on the severity of sinonasal disease remains inconclusive. The objective of this study is to evaluate the impact of CFTR genotype functional classification on sinonasal disease severity in patients with CRS.

Methods

Retrospective chart review of patients with CF who underwent endoscopic sinus surgery for chronic rhinosinusitis from 1998 to 2015. Patients were divided into high- or low-risk genotypes based on standardized CFTR gene functional classification. The primary outcome was the 22-item Sino-Nasal Outcome Test (SNOT-22) score. Secondary outcomes included endoscopic scores, extent of surgery performed, presence of polyposis, number of revision surgeries, and Lund-MacKay computed tomography scores.

Results

Thirty-eight patients harbored a high-risk CFTR genotype, and 11 had a low-risk genotype. On bivariate analysis, there was no association between CFTR genotype risk stratification and measures of preoperative disease severity or postoperative outcomes. There were no associations between genotype risk stratification and outcome variables on multivariate linear regression, adjusted for age and gender. There were significant improvements in several SNOT-22 subdomains before and after endoscopic sinus surgery (P < 0.05), but the magnitude of improvement was not significantly different on the basis of CFTR genotype risk stratification.

Conclusion

High-risk CFTR genotypes are not associated with worse sinonasal disease severity or postoperative symptom control than low-risk CFTR genotypes after adjusting for confounding factors.

Level of Evidence

Level IV. Laryngoscope, 2017

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The role of elective neck dissection in the treatment of maxillary sinus squamous cell carcinoma

Objective

This study is designed to analyze the survival benefits of elective neck dissection (END) in the treatment of squamous cell carcinoma of the maxillary sinus (MS-SCC) with clinically negative neck lymph nodes (N0) and no metastasis (M0).

Study Design

The aim of this study was to evaluate whether END improves survival in patients with MS-SCC.

Methods

This study is a population-based, concurrent retrospective database analysis of patients diagnosed with N0M0 MS-SCC from 2004 to 2013. Data were acquired from the Surveillance, Epidemiology, and End Results database. Frequency functions, Kaplan-Meier and Cox regression models were queried to analyze demographics, treatment status, and survival outcomes.

Results

There were a total of 927 MS-SCC cases in the database between 2004 and 2013. This analysis revealed that for the overall cohort, END significantly and independently reduces the 5-year hazard of death in MS-SCC (hazard ratio [HR] = 0.646, 95% confidence interval [CI] = 0.419–0.873, P = 0.047). For early tumor (T)1/T2 tumors and T4 tumors, END did not independently improve 5-year survival. However, for T3 disease, END significantly reduced the 5-year hazard of death in MS-SCC (HR = 0.471, 95% CI = 0.261–0.680, P = 0.001), regardless of other covariates, including adjuvant radiation. There has been an increase in the percentage of MS-SCC surgeries that have been accompanied by END since SEER started collecting this data, although this did not demonstrate significance (R² = 0.622).

Conclusion

END improves disease-specific survival in patients with MS-SCC size > 4 cm and advanced T-stage (American Joint Committee on Cancer AJCC TIII). Therefore, surgeons performing maxillectomies should consider conducting an END concurrent with maxillectomy for those with size > 4 cm advanced stage cancer.

Level of Evidence

4. Laryngoscope, 2017

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Prevalence of adult unilateral hearing loss and hearing aid use in the United States

Objective

The prevalence of unilateral hearing loss (UHL) in adults has not been well characterized. The objectives of this study are to determine the prevalence of UHL in U.S. adults and its treatment with hearing aids using a nationally representative study.

Study Design

Cross-sectional national epidemiologic study (n = 6,242).

Methods

Subjects ≥ 18 years old with audiometric testing in the 2005 to 2006, 2009 to 2010, and 2011 to 2012 cycles of the National Health and Nutrition Examination Study were included. UHL was defined as normal hearing (≤25 decibels hearing level [dB HL] pure tone average [PTA]) in one ear and at least mild hearing loss (>25 dB HL PTA) in the other ear. Hearing aid usage was defined by at least 5 hours per week (2005–2006) or at least seldom (2009–2012) use. Sampling weights were utilized to ensure generalizability to the U.S. population.

Results

The overall prevalence of UHL in adult Americans was 7.2% (95% confidence interval 6.1%–8.6%), with 5.7% (4.8%–6.7%) having mild and 1.5% (0.1%–2.1%) with moderate-or-worse UHL; nearly one-third of the latter reported trouble hearing. The prevalence of hearing aid usage in those with UHL was 2.0% (0.6%–6.7%). Of those with mild UHL, 1.4% (0.2%–8.0%) used hearing aids. Of those with moderate UHL, 4.2% (0.1%–22%) used hearing aids. Among those with UHL and also at least moderate subjective difficulty hearing, only 11% wore hearing aids.

Conclusion

UHL is common among U.S. adults. Hearing aid usage is very low, even when there is perceived handicap. Public health education is needed to increase awareness of and auditory rehabilitation for UHL.

Level of Evidence

2. Laryngoscope, 2017

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