Current Opinion in Otolaryngology & Head and Neck Surgery最新文献

Purpose of review: Preclinical auditory research uncovers mechanisms underlying hearing loss and reveals novel therapeutic targets. Inner ear gene therapy offers an attractive alternative to current treatments for deafness. An in-depth understanding of the principles of gene therapy is essential to the design of cochlear gene therapy studies, which must be meticulously selected based on the etiology, pathophysiology, and mechanisms of hearing loss. The purpose of our article is to provide an updated and succinct review of cochlear gene therapy.

Recent findings: Advances in molecular technology have enabled numerous proof-of-principle studies in recent years, testing the feasibility of protective, restorative, and regenerative cochlear gene therapy. Recent findings have demonstrated how the delivery of neurotrophic factor transgenes can potentially improve hearing in hidden hearing loss. Restorative gene therapy, carrying the OTOF gene, has restored hearing in human subjects in clinical trials. Additionally, ongoing efforts are underway to regenerate sensory cells in the cochlea using cocktails of transcription factors in postdeafened animal models.

Summary: Recent successes in clinical trials for cochlear gene therapy are encouraging; however, preclinical auditory research remains a high priority and necessity. Future advancements in basic science research may enable the prevention or cure of deafness through cochlear gene therapy.

Purpose of review: The recent successful otoferlin gene therapy trials have refocused the fields attention on the potential of gene therapy to cure hearing loss. With over 100 known monogenetic causes of hearing loss, the key question is which will be the next set of disorders that are treatable. The current review addresses potentially targetable hearing disorders that can be addressed with current gene therapy technologies.

Recent finding: For gene replacement therapy, we need to consider disorders that have residual targetable cells present in postnatal to adult ages. If a target tissue (i.e. hair cells) degenerates during development, it can no longer be rescued by gene therapy. Disorders such as DFNB8 and certain mutations in DFNB1 could benefit from a gene therapy approach. Other important considerations are the size of the gene being replaced, the availability of appropriate vectors, and the overall incidence of the disease.

Summary: Genetic hearing losses that occur in the postnatal period are currently optimal targets and conversely hearing losses that occur in utero resulting in severe to profound congenital losses for now will not be treatable with gene therapy. Gene replacement therapy for recessive disorders will precede development of gene editing strategies for dominant disorders.

Purpose of review: Autoimmune inner ear disease (AIED) is a rare inner ear disorder characterised by fluctuating, progressive, bilateral sensorineural hearing loss that is responsive to immunomodulatory medications. Due to a lack of widely accepted diagnostic criteria its diagnosis remains elusive. Consequently, little is known about its precise aetiology.

Recent findings: A novel classification system for "immune-mediated inner ear disease" (IMIED) has been proposed, which incorporates additional ear pathologies with identified immune components. This acknowledges the breadth of ear conditions that may respond to immune modulation. A range of diagnostic biomarkers are identified with varied clinical efficacy. This is appraised within the full context of a clinical setting to provide insight into practical utility. The efficacy of traditional steroid therapy is re-appraised and remains first-line therapy., The indication for steroid spring therapies is identified, and modern immunomodulatory medications are discussed.

Summary: AIED should be discussed within the spectrum of "immune-mediated inner ear disease", and therapeutic efficacy may be translated along the spectra. Diagnostic biomarkers must be appraised with caution, and diagnosis still relies on responses to steroids. Steroid sparring agents are efficacious for long-term management, and modern biologics show promise, but further investigation is needed.

Purpose of review: We briefly review the history of surgical innovation in free flap reconstruction of the head and neck. With a specific focus on maximizing patient QoL by prioritizing a 'precision reconstruction', we then posit novel avenues for surgical refinement to usher in the next generation of head and neck free flap reconstruction.

Recent findings: Patients undergoing free flap reconstruction of the head and neck increasingly co-prioritize preservation of quality-of-life (QoL) alongside the desire to survive their diagnosis. In the contemporary era, this fact has prompted microvascular surgeons to customize reconstructive plans to minimize decisional regret and maximize favorable functional and cosmetic outcomes for their patients. Increasingly popular strategies for surgical refinement and innovation in this space include novel flap harvest techniques, unconventional flap donor sites, and use of flow-through configurations, all of which are routinely utilized in our group's practice. Additional strategies gaining traction in head and neck reconstruction include vascular perfusion imaging with indocyanine green fluorescence angiography and 'Jaw-in-a-Day' surgeries leveraging computer-aided design (CAD)/computer-aided manufacturing (CAM) technologies.

Summary: The next frontier of innovation in free flap reconstruction of the head and neck will prioritize custom, patient-specific reconstructions that consider the unique anatomic, functional, and aesthetic needs of each patient (i.e. precision reconstruction).

Purpose of review: To review current intraoperative imaging techniques utilized in head and neck reconstruction, with a focus on applications in vascular perfusion assessment, bony reconstruction, and improved intraoperative visualization and education.

Recent findings: In recent years, there have been both technological advances as well as increased implementation of imaging techniques in head and neck reconstruction. To assess for real-time flap perfusion, indocyanine green fluorescence angiography (ICG) has become increasingly adopted, allowing for early identification of vascular compromise and improved flap viability. In bony reconstruction, intraoperative CT and navigation systems have enhanced the precision of osteotomies and hardware placement. Emerging technologies such as the exoscope system have also contributed to improved intraoperative visualization, surgical planning, and education for trainees and multidisciplinary teams.

Summary: Intraoperative imaging continues to advance the safety and precision of head and neck reconstruction. Techniques such as ICG, intraoperative navigation, and augmented visualization tools support better decision-making, reduced complication rates, and enhanced surgical education. Ongoing investigation is needed to standardize protocols, integrate quantitative thresholds for perfusion and bony alignment, and more widely implement technologies.

Purpose of review: There are currently five groups internationally involved in human clinical gene therapy trials for otoferlin-associated hearing loss. This includes (in alphabetical order) the Eye and ENT Hospital Fudan University (China), Lilly-Akouos (USA), Otovia (China), Regeneron (USA), and Sensorion (France). This review summarizes early work that led to these efforts and highlights early published data on clinical outcomes.

Recent findings: While published outcomes are currently limited, data emerging from each of these clinical trials is highly consistent. Using a dual vector approach to reconstitute full length Otoferlin, all groups report varying degrees of hearing improvement following cochlear gene therapy, with some cases of hearing restoration to normal levels. Recent data suggests that improvement is not limited only to young children but also adolescents and even young adults in some cases. The treatments all appear safe with limited adverse effects associated with the therapies reported.

Summary: Gene therapy for otoferlin-related deafness appears highly successful in most cases with limited reported adverse effects or outcomes. This success will undoubtably usher in a new era of gene therapy for other forms of genetic deafness.

Purpose of review: This paper aims to contribute to improved diagnostic accuracy, review outcomes of surgery, and provide guidance on how patients and caregivers are counselled about treatment options for juvenile otosclerosis (JO) and congenital stapes footplate fixation (CSFF).

Recent findings: In JO, there is abnormal bone resorption and recalcification leading to progressive conductive or mixed hearing loss depending on the location of affected bone. There is a higher rate of obliterative otosclerosis in children compared to adults and thus consideration should be given to proceed with earlier surgical intervention, with stapedotomy regarded as a safe option. CSFF occurs due to congenital abnormalities in the annular ligament of the footplate and can be associated with other genetic conditions and syndromes. It is characterized by maximal, nonprogressive conductive hearing loss. Stapedotomy can be curative for hearing loss, though the rate of success is reported to be less than in JO, so hearing aids and implants may be more appropriate in some cases.

Summary: Accurate diagnosis of JO and CSFF is of key importance because outcomes of surgery differ. High resolution computerized tomography of the petrous temporal bones should be performed to confirm diagnosis and to inform risks and benefits of operative intervention. Hearing rehabilitation should be addressed in a timely manner to optimize learning.

Purpose of review: Two-team approaches to head and neck cancer ablation and free flap reconstruction now occur concurrently in most centers. While the functional outcomes after head and neck ablation and reconstruction are typically examined through the lens of the reconstructive surgeon, optimizing the patient's functional outcome requires careful considerations of the entire surgical team. This review summarizes important intraoperative considerations for decision making by the surgical team, with a particular emphasis on ablative considerations, to optimize reconstructive outcomes after tumor extirpation.

Recent findings: Intraoperatively, dynamic and deliberate communication between the ablative and reconstructive surgeons are critical in two-team approaches. Surgical principles such as thoughtful skin incision planning, atraumatic dissection of neck vessels, preservation of draining veins in the neck, preservation of nerves to maximize sensation of the native tissue, atraumatic handling of native mucosa, and communication in planning osteotomies of the mandible and maxilla may help to optimize functional outcomes after reconstruction.

Summary: In two-team approaches to head and neck cancer ablation and free flap reconstruction, a focus on communication, flexibility, and trust between surgeons are of paramount importance. Importantly, the goals of the ablative and reconstructive surgeons are interdependent, yet in our experience, optimal reconstructive outcomes begin with the thoughtful peri-operative decision-making and intraoperative preservation of critical structures by the surgical team.

Purpose of review: To review the updated literature on middle ear adenomatous neuroendocrine tumors (MEANTS) and to discuss advances in classification, diagnosis, and management of these tumors.

Recent findings: The WHO updated its classification of head and neck neuroendocrine neoplasms in 2022. We discuss this classification system, and its implications on the diagnosis of these tumors from a histological and molecular perspective. Furthermore, this framework helps with our understanding of their clinical course and hence management.

Summary: In 2022, WHO classified head and neck neuroendocrine neoplasms into well differentiated neuroendocrine tumors (NET) (G1-G3, based on mitotic count/Ki67) and high-grade neuroendocrine carcinoma (NEC) (small/large cell), based on differentiation, atypia, and marker expression. Aside from histological characteristics, the WHO classification distinguishes NETs (site-specific epigenetic changes) from NECs (TP53/RB1 alterations). Small cell NECs show biallelic TP53/RB1 inactivation; large cell NECs are heterogeneous. Molecular profiling helps differentiate NET G3 from NEC. Recent reviews have shown higher rates of recurrence than previous studies, emphasizing the need for surgical modification based on tumor extent and biology, and for indefinite surveillance.