Current Opinion in Otolaryngology 2020-10-01

Editorial introductions

Publicatie 01-10-2020


No abstract available

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Editorial: Legacy and the Future

Samy, Ravi N.

Publicatie 01-10-2020


No abstract available

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A design-thinking approach to therapeutic translation: tympanic regeneration

Santa Maria, Peter Luke

Publicatie 01-10-2020


Purpose of review Clinician researchers face the pressures of meeting academic benchmarks combined with advancing new therapies to patients. The vast majority of drug discoveries fail in translation. A new method of meeting the challenges of preclinical therapeutic translation is presented using the example of tympanic regeneration.Recent findings The key to a design-thinking approach to therapeutic translation is to ‘begin with the end in mind’ by widening the scope of the problem, with multiple points of view, to not only understand the disease but the context for the patient and the health system in which it occurs. Idea for therapeutics should be tested in relevant models early and once proof of efficacy is established, translational milestones that represent the greatest risk, such as safety and toxicity should be addressed first. It is important to seek the feedback of industry early to understand what milestones should be best addressed next with limited academic resources. Whenever proceeding, guidelines for maintaining scientific reproducibility should be followed to minimize risk of failure during transfer into industry.Summary A Design-thinking approach addresses the potential failures in drug discovery and preclinical translation.

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Oncolytic virotherapy: a potential therapeutic approach for cholesteatoma

Lipschitz, Noga; Earl, Brian R.; Cripe, Timothy P.; Samy, Ravi N.

Publicatie 01-10-2020


Purpose of review To review the principles of oncolytic virotherapy and summarize the recent preliminary evidence on the efficacy of oncolytic virotherapy for cholesteatoma (CHST) treatment in vitro in human CHST cells and in a gerbil CHST model.Recent findings The use of oncolytic virotherapy for nonmalignant lesions is innovative. In-vitro results showed that oncolytic herpes simplex virus 1 (oHSV) selectively targets and kills CHST cells. In a gerbil model of CHST, local oHSV injections were associated with a decrease in CHST volume and modulation of bony changes.Summary Surgical treatment options for CHST are limited by high morbidity and recidivism, emphasizing the need for developing treatment alternatives. Preliminary results support the potential therapeutic effect of oncolytic virotherapy on CHST, yet further research is needed to evaluate this novel approach.

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Insulin-like growth factor 1: role in the auditory system and therapeutic potential in otology

Gao, Li; Nakagawa, Takayuki

Publicatie 01-10-2020


Purpose of review Insulin-like growth factor 1 (IGF-1) is a hormone necessary for the development, growth, and maintenance of various organs, and has been used as a therapeutic agent in clinical settings. This review aimed to illustrate its role in the auditory systems and its potential use as a therapeutic in the field of otology.Recent findings Previous animal studies have indicated the critical role of IGF-1 in the development and maintenance of the auditory system, especially in the cochlea. A clinical study demonstrated a close relationship between the serum level of IGF-1 and the progression of age-related hearing impairment, suggesting its importance in the maintenance of hearing in humans. More recently, its effect on the regeneration of cochlear synapses has been reported using explant cultures, which could explain the course of hearing recovery in patients who underwent topical IGF-1 application for the treatment of sudden sensorineural hearing loss.Summary Recent advances in experimental and clinical investigations have revealed the importance of IGF-1 in the maintenance of the auditory function. On the basis of broad targets, its clinical application will expand to the field of otology in the future.

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Keratinocyte growth factor signaling promotes stem/progenitor cell proliferation under p63 expression during middle ear cholesteatoma formation

Yamamoto-Fukuda, Tomomi; Akiyama, Naotaro

Publicatie 01-10-2020


Purpose of review Middle ear cholesteatoma is an epithelial lesion that expands into the middle ear, resulting in bone destruction. However, the pathogenesis of this has been unknown. The purpose of this review is to understand the role of keratinocyte growth factor (KGF) during epithelial stem and/or progenitor cell proliferation in middle ear cholesteatoma.Recent findings Many researchers have investigated the molecular mechanism of middle ear cholesteatoma to establish a conservative treatment. Recently, some studies have focused on the stem cells of middle ear cholesteatoma and their detection, but the key molecules for stem cell formation were not shown.Summary We established an animal model for middle ear cholesteatoma and are showing the results of our studies. KGF expression accelerates the proliferation of stem/progenitor cells through the induction of transcription factor p63 expression in the epithelium of the tympanic membrane and mucosal epithelium overlying the promontory of the cochlea and within the attic. This is typical in middle ear cholesteatoma. Moreover, the partial epithelial–mesenchymal transition under the p63 signaling pathway plays an essential role in epithelial cell growth in middle ear cholesteatoma formation. Understanding p63 expression following KGF expression and associated signaling events can improve therapeutic outcomes in patients with middle ear cholesteatoma.

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Optical coherence tomography: current and future clinical applications in otology

Matthews, Timothy James; Adamson, Robert

Publicatie 01-10-2020


Purpose of review This article reviews literature on the use of optical coherence tomography (OCT) in otology and provides the reader with a timely update on its current clinical and research applications. The discussion focuses on the principles of OCT, the use of the technology for the diagnosis of middle ear disease and for the delineation of in-vivo cochlear microarchitecture and function.Recent findings Recent advances in OCT include the measurement of structural and vibratory properties of the tympanic membrane, ossicles and inner ear in healthy and diseased states. Accurate, noninvasive diagnosis of middle ear disease, such as otosclerosis and acute otitis media using OCT, has been validated in clinical studies, whereas inner ear OCT imaging remains at the preclinical stage. The development of recent microscopic, otoscopic and endoscopic systems to address clinical and research problems is reviewed.Summary OCT is a real-time, noninvasive, nonionizing, point-of-care imaging modality capable of imaging ear structures in vivo. Although current clinical systems are mainly focused on middle ear imaging, OCT has also been shown to have the ability to identify inner ear disease, an exciting possibility that will become increasingly relevant with the advent of targeted inner ear therapies.

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Current imaging tools for vestibular schwannoma

Dang, Linh; Tu, Nathan Chin-yau; Chan, Eleanor Y.

Publicatie 01-10-2020


Purpose of review Of the tumors found in the cerebellopontine angle (CPA), vestibular schwannomas are by far the most common. Modern diagnostic imaging enables excellent visualization of the CPA and detection of very small tumors while optimizing patient comfort and time. This review addresses the current imaging tools available for diagnosis of vestibular schwannomas.Recent findings The current gold-standard imaging study for vestibular schwannomas is a gadolinium-enhanced T1-weighted MRI. The yield of this expensive study is only about 3–4% given the low incidence of vestibular schwannomas, thus there is utility in screening with noncontrast T2-weighted MRI, which is a quicker and more economical study.Summary Vestibular schwannomas are best evaluated with gadolinium-enhanced T1-weighted MRI, which can detect tumors as small as 2–3 mm. Recent studies have found that the reported sensitivity and specificity of noncontrast MRI is almost equivalent to that of gadolinium-enhanced T1-weighted MRI. As such, this modality is increasingly being adopted by institutions for both diagnosis and surveillance of vestibular schwannomas and shows promise for broader implementation. Newer protocols, such as FLAIR and DTI may provide additional information and further aid preoperative counseling and surgical planning in the future.

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Bone conduction implants

Richards, John P.; Symms, John T.; Beasley, Kerry; Coffman, Heather M.S.

Publicatie 01-10-2020


Purpose of review To discuss the different types of bone conduction implants available today and describe the types of hearing loss that could benefit from bone conduction implants.Recent findings Bone conduction implants have been used successfully for over two decades. However, there have been barriers to their use because of skin complications and limited high-frequency hearing gains. Recently developed technologies, such as active bone conduction implants may overcome some of these limitations, potentially opening the door for improved aided benefit and increased patient satisfaction from bone conduction amplification.Summary A variety of bone conduction implants currently exist, with suitable amplification options available for many different types and severities of hearing loss and patient preferences.

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State of the art regeneration of the tympanic membrane

Sagiv, Doron; Chin, Oliver Y.; Diaz, Rodney C.; Brodie, Hilary A.

Publicatie 01-10-2020


Purpose of review One of the most common diseases of the tympanic membrane is a perforation, and tympanoplasty is one of the more common procedures in otolaryngology. Tympanic membrane regeneration and bioengineering aim to improve the success rate of the procedure, increase the availability of different scaffolds and provide innovative tools that will simplify the surgical technique and make it accessible for surgeons with varying expertise level. This review aims to raise awareness of current tissue engineering developments in tympanic membrane regeneration and how they may augment current clinical practices. We focus here on achievements in tympanic membrane cell cultures and on innovations in development of new scaffolds and growth factors that enhance regeneration of patients native tympanic membranes.Recent findings In recent years, great achievements were reached in the field of tympanic membrane regeneration in the three hallmarks of bioengineering: cells, scaffolds and bioactive molecules. New techniques for modeling normal tympanic membrane proliferation were developed, as well as for isolation and expansion of normal tympanic membrane keratinocytes from miniature samples of scarred tissue. Ongoing clinical trials aim to seal the perforation by applying different scaffolds infiltrated by growth factors on the tympanic membrane.Summary Research efforts in tympanic membrane regeneration continue to seek the ideal single tissue-engineered substitute. Recent advances in tympanic membrane bioengineering include new types of scaffolds that may augment and provide a safe and effective alternative to the current gold-standard autograft. New bioactive molecules may simplify the surgical procedure and reduce surgical time by augmenting the native tympanic membrane regeneration. Several groups of bioengineering scientists and neurotologists are continuing to move forward and develop new strategies, seeking to create a fully functional tissue-engineered tympanic membrane.

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Microtechnologies for inner ear drug delivery

Forouzandeh, Farzad; Borkholder, David A.

Publicatie 01-10-2020


Purpose of review Treatment of auditory dysfunction is dependent on inner ear drug delivery, with microtechnologies playing an increasingly important role in cochlear access and pharmacokinetic profile control. This review examines recent developments in the field for clinical and animal research environments.Recent findings Micropump technologies are being developed for dynamic control of flow rates with refillable reservoirs enabling timed delivery of multiple agents for protection or regeneration therapies. These micropumps can be combined with cochlear implants with integral catheters or used independently with cochleostomy or round window membrane (RWM) delivery modalities for therapy development in animal models. Sustained release of steroids with coated cochlear implants remains an active research area with first-time-in-human demonstration of reduced electrode impedances. Advanced coatings containing neurotrophin producing cells have enhanced spiral ganglion neuron survival in animal models, and have proven safe in a human study. Microneedles have emerged for controlled microperforation of the RWM for significant enhancement in permeability, combinable with emerging matrix formulations that optimize biological interaction and drug release kinetics.Summary Microsystem technologies are providing enhanced and more controlled access to the inner ear for advanced drug delivery approaches, alone and in conjunction with cochlear implants.

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The case for cochlear implantation in unilateral and asymmetric sensorineural hearing loss

Bojrab, Dennis; Hong, Robert S.

Publicatie 01-10-2020


Purpose of review Cochlear implants have been used to treat bilateral deafness for over 40 years. A more recent development has been the application of this technology toward single-sided deafness (SSD) and asymmetric hearing loss (AHL), culminating in the Food and Drug Administration (FDA) approval in the United States for this indication in July of 2019. This review examines the recent literature on cochlear implants for SSD and AHL, focusing on speech perception, sound localization, tinnitus, and quality of life.Recent findings There is an expanding body of literature supporting the use of cochlear implant in SSD/AHL patients. The cochlear implant offers a unique rehabilitation option for this subset of patients as it potentially restores binaural hearing (direct stimulation of both ears). A review of the literature reveals significant improvements with the cochlear implant in speech perception in quiet and noise, sound localization, tinnitus, and quality of life. In addition, these improvements appear to be greater than what conventional options such as a contralateral routing of signal (CROS) hearing aid and bone conduction device (BCD) are able to achieve.Summary Cochlear implants offer additional benefits over previously available options of CROS and BCDs and have recently been approved by the FDA for use in patient with SSD/AHL. Given the growing body of literature demonstrating the benefit of cochlear implant over other devices, it is important to offer cochlear implant as an option to these patients.

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Asymmetric sensorineural hearing loss and vestibular schwannoma: when to image?

Conley, Morgan; Diaz, Rodney C.

Publicatie 01-10-2020


Purpose of review We review the literature on the use of audiometric protocols in the guidance of when to obtain MRI for detection of vestibular schwannoma. This discussion will focus on the sensitivity, specificity, and cost-effective analysis of audiometric criteria of asymmetric sensorineural hearing loss (ASNHL) when used to decide when MRI scans should be performed.Recent findings The sensitivity for detecting vestibular schwannomas when invoking published audiometric protocols for triggering MRI acquisition in ASNHL ranged from 50 to 100%. Specificity of these protocols ranged from 23 to 83%. Such audiometric protocols are efficient, achieving sensitivity and specificity at these rates while reducing the screening rate to 18 to 35%. The reduced procurement of MRI while using such audiometric protocols is associated with annual cost savings of between 23 and 82%. While no definitive recommendations can be made from this review, some audiometric protocols offer a better balance of sensitivity and specificity than others.Summary Audiometric protocols for triggering MRI acquisition in ASNHL for evaluation of vestibular schwannoma can be both sensitive and specific. These are competitive measures, and so no protocol is both 100% sensitive and specific. Such protocols become less effective in populations with increased incidence of noise-induced hearing loss. Invocation of such audiometric protocols can considerably reduce the annual cost of MRI evaluation for vestibular schwannomas.

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Current management of superior semicircular canal dehiscence syndrome

Walsh, Erika McCarty

Publicatie 01-10-2020


Purpose of review The current article reviews literature on the contemporary management of superior semicircular canal dehiscence syndrome (SSCDS). Approaches to management and surgical techniques are compared along with a discussion of the use of more standardized, objective outcome measures.Recent findings Considerable debate still exists as to what approach and technique is most appropriate for patients with SSCDS and how to best measure postoperative outcomes. However, it is increasingly accepted that multiple factors account for outcomes in SSCDS, including presenting symptoms and presence of vestibular comorbidities. Therefore, surgical intervention is best tailored to each individual patient. Data on SSCDS outcomes is heterogenous, and increased emphasis is being placed on validated measures of outcome. Round window approaches remain controversial and their role is still undefined.Summary The treatment strategies for SSCDS continue to diversify. A patient-specific approach with systematic documentation of outcomes will continue to inform how these patients are best managed.

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Nerve grafts in head and neck reconstruction

Hoshal, Steven G.; Solis, Roberto N.; Bewley, Arnaud F.

Publicatie 01-10-2020


Purpose of review This article reviews recent literature on repair of peripheral nerve injuries in the head and neck with a focus on autografts, allografts, nerve conduits, and technical considerations.Recent findings Contemporary nerve grafting techniques offer the potential to improve peripheral nerve outcomes and reduce donor site morbidity. A variety of donor nerves autografts have been described that offer favorable outcomes for segmental reconstruction of facial nerve defects. Recent studies have demonstrated promising results in repair of inferior alveolar nerve injuries with human allografts. Animal models describe successful reinnervation of small defects with neural conduits. The latest data do not favor protocolled nerve graft polarity or use of a motor versus sensory donor nerves.Summary Interposition nerve grafting is the gold standard for repair of peripheral nerve injuries when a tension-free primary neurorrhaphy is not possible. Autografts are the work-horse for the majority of head and neck neural defects, however, can result in some degree of donor site morbidity. Recent developments in allografting and neural conduits have the potential to further diversify the head and neck reconstructive surgeons armamentarium. It is unclear if nerve graft makeup or polarity affect functional outcome.

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Reconstructive options following orbital exenteration

Yesensky, Jessica; Lebo, Nicole

Publicatie 01-10-2020


Purpose of review The purpose of this review is to examine current trends in reconstruction following orbital exenteration. Defects ranging from isolated exenteration to more complex midface resections are explored.Recent findings Goals of reconstruction include separating the sino-orbital cavities and creating a safe, stable wound that can withstand adjuvant radiation. When planning for orbital rehabilitation, it is important to create a concave cavity that can accommodate a prosthesis. This is primarily achieved through secondary granulation or split-thickness skin grafts. Recently, the use of dermal allografts has been investigated and shown good success with epithelization of the orbital cavity. For complex orbitomaxillectomy defects, musculocutaneous free tissue flaps remain the mainstay for reconstruction.Summary Reconstructive options following orbital exenteration are based on extent of the defect, need for postoperative radiation, and plans for orbital rehabilitation with prosthesis.

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Current opinions in otolaryngology and head and neck surgery: functional considerations in reconstruction after laryngectomy

Elson, Nora C.; Martinez, Daniel C.; Cervenka, Brian P.

Publicatie 01-10-2020


Purpose of review To review reconstruction techniques following total laryngectomy, partial laryngopharyngectomy, and total laryngopharyngectomy with an emphasis on long-term swallow and speech outcomes.Recent findings Recent literature has shown that the use of fasciocutaneous free flaps in the reconstruction of laryngectomy defects may lead to improved speech and swallow outcomes as compared with regional or free musculocutaneous flaps. Radial forearm and anterolateral thigh are the most often used fasciocutaneous free flaps, with similar speech and swallow outcomes. Primary closure with myofascial flap onlay yields similar speech and swallow results to fasciocutaneous flaps following laryngectomy that spares sufficient pharyngeal mucosa.Summary Whenever reconstructing a salvage laryngectomy defect or a primary laryngectomy defect with mucosal deficiency, current evidence suggests that a fasciocutaneous free flap used to augment pharyngeal volume both improves fistula rates as well as long-term speech and swallow outcomes. When sufficient pharyngeal mucosa is present, myofascial onlay can be considered as well.

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The lateral arm free flap for head and neck reconstruction

Amin, Julian D.; Amin, Neha; Hatten, Kyle M.

Publicatie 01-10-2020


Purpose of review The aim of this study was to review the recent literature on the utilization of the lateral arm free flap use in head and neck reconstruction.Recent findings The lateral arm free flap provides a reliable fasciocutaneous free tissue transfer option ideally suited for reconstruction of the oral cavity, pharynx and parotid. Primary donor site closure, compartmentalized fat and excellent colour match make it an excellent option for head and neck reconstruction. Donor site morbidity is low, and the primary limitation is the short and narrow vascular pedicle.Summary The lateral arm free flap should be considered in cases of oral cavity and skin reconstruction, particularly in cases wherein pedicle length is not restrictive.

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