Sensory cell regeneration and stem cells: what we have already achieved in the management of deafness.

BACKGROUND/OBJECTIVE: Genetic manipulation of the cell-cycle exit, induction of new hair cells (HCs) through gene modification therapy, and introduction of stem cells (SCs) into damaged cochleas potentially offer exciting new strategies in treating sensorineural hearing loss. MATERIALS AND METHODS: Literature review from Medline and database sources. STUDY SELECTION: Ex vivo models, animal studies, in vitro studies, and review articles. DATA SYNTHESIS: Embryonic SCs, neural SCs, or bone marrow SCs survive in the mammalian inner ear after transplantation. The scala media and the modiolus seem more functionally appropriate injection sites. The clear evidence that transplanted neural SCs can adopt the morphologic phenotypes of HCs was the most significant milestone achieved in the related research. The normal cytoarchitecture in the organ of Corti may also be restored through mouse atonal homologue 1 transgene expression and transduction of the nonsensory cells, producing clinically measured improvement in hearing thresholds. Embryonic SC-derived neurons have the potential for synapse formation with auditory HCs and reinnervation of the auditory epithelia. However, fluctuations in survival rates, functional recovery of the spiral-ganglion neurons, integration to the host tissue, and potential immune barriers are also areas of utmost importance. CONCLUSION: There is an already exciting progress in the fields of sensory cell regeneration and SC research in an attempt to restore hearing or prevent deafness. However, further understanding of the underlying mechanisms of auditory genetics, continuing investigation of the human genome, refinement of the delivering techniques, and specification of the therapeutic strategies have to be developed before functional regeneration of the cochlea can be achieved in clinical practice.

Biofilms in ear, nose, and throat infections: how important are they?

BACKGROUND: Biofilms present a new challenging concept in sustaining chronic, common antibiotic-resistant ear, nose, and throat (ENT) infections. They are communities of sessile bacteria embedded in a matrix of extracellular polymeric substances of their own synthesis that adhere to a foreign body or a mucosal surface with impaired host defense. The aim of this paper is to review the literature on ENT diseases that can be attributed to biofilm formation and to discuss options for future treatment. MATERIALS AND METHODS: Literature review from Medline and database sources. Electronic links and related books were also included. STUDY SELECTION: Controlled clinical trials, animal models, ex vivo models, laboratory studies, retrospective studies, and systematic reviews. DATA SYNTHESIS: Biofilm formation is a dynamic five-step process guided by interbacterial communicating systems. Bacteria in biofilms express different genes and have markedly different phenotypes from their planktonic counterparts. Detachment of cells, production of endotoxin, increased resistance to the host immune system, and provision of a niche for the generation of resistant organisms are biofilm processes that could initiate the infection process. Effective prevention and management strategies include interruption of quorum sensing, inhibition of related genes, disruption of the protective extrapolymer matrix, macrolides (clarithromycin and erythromycin), and mechanical debridement of the biofilm-bearing tissues. With regard to medical indwelling devices, surface treatment of fluoroplastic grommets and redesign of cochlear implants could minimize initial microbial colonization. CONCLUSION: As the role of biofilms in human infection becomes better defined, ENT surgeons should be prepared to deal with their unique and tenacious nature.

Grommets in otitis media with effusion: the most frequent operation in children. But is it associated with significant complications?

INTRODUCTION: Otitis media with effusion is one of the most frequent diseases in children, and its management requires the attention of general practitioners, pediatricians and ear, nose and throat (ENT) surgeons. The main complications associated with tympanostomy tube insertion, are: (1) purulent otorrhea (10-26% of cases), in which local otic preparations might be effective, and biofilm-resistant tubes may decrease this complication in the future; (2) myringosclerosis (39-65% of operated ears), with usually no serious sequelae; (3) segmental atrophy (16-75% of cases); (4) atrophic scars and pars flaccida retraction pockets (28 and 21% of operated ears, respectively); (5) tympanic membrane perforations (3% of cases, although with T-tubes, the incidence may be as high as 24%); (6) cholesteatoma (1% of cases), although tympanostomy tubes may sometimes prevent, rather than contribute to its development; (7) granulation tissue (5-40% of instances), when the duration of tube retention is prolonged. CONCLUSION: It would appear that the complications associated with tympanostomy tube insertion are more frequent than anticipated, reaching 80% of operated ears under specific circumstances and in certain subgroups of children. These complications may resolve with conservative management, but in persistent cases surgical removal of the tubes is mandatory.

Intratympanic steroid treatment in idiopathic sudden sensorineural hearing loss: a control study.

BACKGROUND AND OBJECTIVE: Although systemic steroids in sudden sensorineural hearing loss (SSHL) appears to be the most effective and the most widely accepted treatment today, a significant number of patients do not respond to steroid treatment or they cannot receive steroids for medical reasons. Intratympanic (IT) administration of steroids appears to be an alternative or additional method of management without the side effects of intravenous steroids. The aim of this study is to investigate the effectiveness and safeness of IT administration of steroids in patients who had not responded to IV treatment and to compare treatment efficacy with controls. STUDY DESIGN AND SETTING: Our study consisted of 37 patients with SSHL who, at the end of 10 days of therapy with intravenous steroids as a 1st line treatment, had pure-tone 4-frequency (0.5, 1, 2, and 4 kHz) average (PTA) of worse than 30 dB or worse than 10 dB from the contralateral ear (defined as failed intravenous treatment). They were randomized into 2 groups, treatment and control. The 19 patients of the treatment group received approximately 0.5 mL sterile aqueous suspension of methylprednisolone acetate in a concentration of 80 mg/2 mL by direct injection. The procedure was carried out 4 times within a 15-day period. An audiogram was performed before each injection and approximately 1.5 months after the last session. RESULTS: All patients tolerated the procedure well. No perforation or infection was noticed in any of the patients at their last visit. With regard to the 19 patients who received intratympanic treatment, in 9 patients, the PTA threshold improved more than 10 db, in 10 patients there was no change greater than 10 db, and no patients deteriorated more than 10 db. In the control group, none of the patients showed any change greater than 10 db. The difference was statistically significant (P = 0.002). The treatment group showed an improvement in mean PTA of 14.9 dB, whereas the control group showed a deterioration of 0.8 dB, and this difference also was statistically significant (P = 0.0005). IT treatment (P = 0.0001), better post-IV PTA (P = 0.0008), and absence of vertigo (P = 0.02) were good predictors of the outcome. In contrast, sex, age, affected ear, days to admission, and pattern of the initial audiogram showed no significant influence on the outcome. CONCLUSION AND SIGNIFICANCE: IT steroid administration after failed intravenous steroids is a safe and effective treatment in sudden sensorineural hearing loss.

Recurrent ceruminous adenocarcinoma of the external auditory canal.

Ceruminous adenocarcinoma is a rare malignant neoplasm of the glandular structures of the external auditory canal. The true incidence and behavior of these rare tumors are still unclear due to confusing terminology, classification and histological definitions. Therefore, the ENT surgeon faces major difficulties in choosing the method of management--conservative or more radical surgery--with the addition or not of radiotherapy. We report a 57-year-old male patient with a recurrence of a previously excised (maybe partially) and irradiated ceruminous adenocarcinoma of the right external auditory canal. Aggressive surgery was considered as the treatment of choice. However, the patient refused this approach and, as a consequence, a conservative excision was performed but with histologically confirmed healthy margins. To our surprise, the patient showed an excellent response and he is disease free 3 years following the last operation. Although recurrences usually occur within months after inadequate management, some may happen even 7 years post treatment. Therefore, routine long-term follow-up was advised.