Adenoid cystic carcinoma of the head and neck--An update.

As more and more substances have been shown in preclinical studies to be capable of preventing damage to the inner ear from exposure to noise, ototoxic drugs, ischemia, infection, inflammation, mechanical trauma and other insults, it is becoming very important to develop feasible and safe methods for the targeted delivery of drugs to specific regions in the inner ear. Recently developed methods for sampling perilymph from the cochlea have overcome major technical problems that have distorted previous pharmacokinetic studies of the ear. These measurements show that drug distribution in perilymph is dominated by passive diffusion, resulting in large gradients along the cochlea when drugs are applied intratympanically. Therefore, in order to direct drugs to specific regions of the ear, a variety of delivery strategies are required. To target drugs to the basal cochlear turn and vestibular system while minimizing exposure of the apical cochlear turns, single one-shot intratympanic applications are effective. To increase the amount of drug reaching the apical cochlear turns, repeated intratympanic injections or controlled-release drug delivery systems, such as biodegradable biopolymers or catheters and pumps, are more effective. However, if the applied substance does not easily pass through the round window membrane, or if a more widespread distribution of drug in the ear is required, then intralabyrinthine injections of the substance may be required. Intralabyrinthine injection procedures, which are currently in development in animals, have not yet been proven safe enough for human use.

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Principles of local drug delivery to the inner ear.

The capacity of adult mammals to regenerate sensory hair cells is not well defined. To explore early steps in this process, we examined reactivation of a transiently expressed developmental gene, Atoh1, in adult mouse utricles after neomycin-induced hair cell death in culture. Using an adenoviral reporter for Atoh1 enhancer, we found that Atoh1 transcription is activated in some hair cell progenitors (supporting cells) 3 d after neomycin treatment. By 18 d after neomycin, the number of cells with Atoh1 transcriptional activity increased significantly, but few cells acquired hair cell features (i.e., accumulated ATOH1 or myosin VIIa protein or developed stereocilia). Treatment with DAPT, an inhibitor of γ-secretase, reduced notch pathway activity, enhanced Atoh1 transcriptional activity, and dramatically increased the number of Atoh1-expressing cells with hair cell features, but only in the striolar/juxtastriolar region. Similar effects were seen with TAPI-1, an inhibitor of another enzyme required for notch activity (TACE). Division of supporting cells was rare in any control or DAPT-treated utricles. This study shows that mature mammals have a natural capacity to initiate vestibular hair cell regeneration and suggests that regional notch activity is a significant inhibitor of direct transdifferentiation of supporting cells into hair cells following damage.

https://www.jneurosci.org/content/jneuro/31/43/15329.full.pdf

Inhibition Of Notch Activity Promotes Nonmitotic Regeneration of Hair Cells in the Adult Mouse Utricles

Tumor angiogenesis and lymphangiogenesis: tumor/endothelial crosstalk and cellular/microenvironmental signaling mechanisms.

Sensory hair cells are mechanoreceptors of the auditory and vestibular systems and are crucial for hearing and balance. In adult mammals, auditory hair cells are unable to regenerate, and damage to these cells results in permanent hearing loss. By contrast, hair cells in the chick cochlea and the zebrafish lateral line are able to regenerate, prompting studies into the signaling pathways, morphogen gradients and transcription factors that regulate hair cell development and regeneration in various species. Here, we review these findings and discuss how various signaling pathways and factors function to modulate sensory hair cell development and regeneration. By comparing and contrasting development and regeneration, we also highlight the utility and limitations of using defined developmental cues to drive mammalian hair cell regeneration.

/pdf/sensory-hair-cell-development-and-regeneration-similarities-350tbrnn1l.pdf

Sensory hair cell development and regeneration: similarities and differences

OBJECTIVE: To evaluate surgical outcomes for squamous cell carcinoma of the temporal bone. STUDY DESIGN: Retrospective study. SETTING: Eye and ENT Hospital. METHODS: Seventy-two patients with squamous cell carcinoma of the temporal bone were analyzed for survival. The patients were staged according to the modified Pittsburgh staging system. Five patients with T1 cancers underwent local resection (LR), and 10 patients with T1 cancers underwent lateral temporal bone resection (LTBR). Two patients with T2 cancers underwent LR, and 1 patient with T2 cancer underwent LTBR. One patient with T3 cancer underwent LR, 8 patients with T3 cancers underwent LTBR, and 10 patients with T3 cancers underwent subtotal temporal bone resection (STBR). Ten patients with T4 cancers underwent LTBR, and 25 patients with T4 cancers underwent STBR. RESULTS: Of all patients that underwent surgery, 18 died of their disease during the follow-up time. The 5-year survival rates of patients with T stages 1 through 4 were 100%, 67%, 21%, and 14%, respectively. There was no statistically significant difference in 5-year survival rate between T3 and T4 using the log-rank test (p > 0.05). The 5-year survival rates after LTBR and STBR for T3 were 26% and 16% (p > 0.05), respectively, and those for T4 were 17% and 11% (p > 0.05), respectively. CONCLUSION: An en bloc resection is favored in an effort to produce negative surgical margins for squamous cell carcinoma of the temporal bone. Adjunctive radiotherapy is used for advanced lesions.

Survival outcomes in surgical treatment of 72 cases of squamous cell carcinoma of the temporal bone.

Objectives/Hypothesis:

To determine whether aggressive surgical management is more effective than local canal resection (LCR) for early-stage temporal bone malignancies.



Study Design:

Retrospective study.



Methods:

Forty-three cases of early-stage external auditory canal (EAC) carcinoma who received surgical management between 1993 and 2011 were reviewed. Preoperative computed tomography, enhanced magnetic resonance imaging, pure-tone audiometry, and biopsy were performed. Patients underwent either LCR or lateral temporal bone resection (LTBR). Postoperative pathologic examinations were conducted on all specimens, including assessment of margin status. The duration of the postoperative follow-up period ranged from 6 months to 18 years.



Results:

Of 26 patients who underwent LCR, 10 were stage T1 and 16 were T2. Positive surgical margins were identified in 14 patients. During the follow-up, 12 patients developed recurrence. Of 17 patients who underwent LTBR with superficial parotidectomy, six were stage T1 and 11 were T2. The lateral EAC margins were negative in all 17 patients. In 2/6 T1 patients and in 5/11 T2 patients, tumor cells were identified deep within the EAC cartilage and parotid gland. All of the patients who underwent LTBR survived without evidence of recurrence.



Conclusions:

LTBR with superficial parotidectomy offers the greatest chance of cure for early-stage EAC carcinoma. Intraoperative frozen sections are necessary to determine the tumor-free lateral EAC margins. Postoperative radiotherapy is not strongly recommended for early-stage EAC carcinoma after LTBR. Laryngoscope, 2013

Evidence‐based surgical management of T1 or T2 temporal bone malignancies

Objective:To present diverse symptoms, signs, and findings on diagnostic tests of 11 patients with superior semicircular canal dehiscence (SSCD) syndrome and surgical treatments for dehiscence of 3 patients.Study Design:Retrospective case review.Setting:Tertiary neurotologic and audiologic center.Pa

Variety of audiologic manifestations in patients with superior semicircular canal dehiscence.

Ectopic hair cell-like cell induction by Math1 mainly involves direct transdifferentiation in neonatal mammalian cochlea

OBJECTIVES The purpose of this study was to develop a deep-learning framework for the diagnosis of chronic otitis media (COM) based on temporal bone computed tomography (CT) scans. DESIGN A total of 562 COM patients with 672 temporal bone CT scans of both ears were included. The final dataset consisted of 1147 ears, and each of them was assigned with a ground truth label from one of the 3 conditions: normal, chronic suppurative otitis media, and cholesteatoma. A random selection of 85% dataset (n = 975) was used for training and validation. The framework contained two deep-learning networks with distinct functions: a region proposal network for extracting regions of interest from 2-dimensional CT slices; and a classification network for diagnosis of COM based on the extracted regions. The performance of this framework was evaluated on the remaining 15% dataset (n = 172) and compared with that of 6 clinical experts who read the same CT images only. The panel included 2 otologists, 3 otolaryngologists, and 1 radiologist. RESULTS The area under the receiver operating characteristic curve of the artificial intelligence model in classifying COM versus normal was 0.92, with sensitivity (83.3%) and specificity (91.4%) exceeding the averages of clinical experts (81.1% and 88.8%, respectively). In a 3-class classification task, this network had higher overall accuracy (76.7% versus 73.8%), higher recall rates in identifying chronic suppurative otitis media (75% versus 70%) and cholesteatoma (76% versus 53%) cases, and superior consistency in duplicated cases (100% versus 81%) compared with clinical experts. CONCLUSIONS This article presented a deep-learning framework that automatically extracted the region of interest from two-dimensional temporal bone CT slices and made diagnosis of COM. The performance of this model was comparable and, in some cases, superior to that of clinical experts. These results implied a promising prospect for clinical application of artificial intelligence in the diagnosis of COM based on CT images.

Fang-Lu Chi

Papers

Survival outcomes in surgical treatment of 72 cases of squamous cell carcinoma of the temporal bone.

Evidence‐based surgical management of T1 or T2 temporal bone malignancies

Variety of audiologic manifestations in patients with superior semicircular canal dehiscence.

Ectopic hair cell-like cell induction by Math1 mainly involves direct transdifferentiation in neonatal mammalian cochlea

Deep Learning in Automated Region Proposal and Diagnosis of Chronic Otitis Media Based on Computed Tomography.