Cochlear Implant Outcomes in Large Vestibular Aqueduct Syndrome—Should We Provide Cochlear Implants Earlier? Objective: Examine postoperative speech perception outcomes in a large vestibular aqueduct syndrome (LVAS) patients at a major cochlear implantation center. Study Design: Retrospective analysis of the Sydney Cochlear Implant Centre (SCIC) database and medical records from January 1994 to December 2015 was performed. Setting: Tertiary referral center. Patients: Patients with a diagnosis of LVAS who received a cochlear implant (CI). Only those with speech perception outcomes recorded at least 12 months post implant were included in our analysis. Intervention(s): Therapeutic. Main Outcome Measure(s): Postoperative speech perception scores. Results: Between 1994 and 2015, 176 adult and pediatric patients with a diagnosis of LVAS underwent cochlear implantation at SCIC. Postoperative Bamford-Kowal Bench (BKB) sentence test scores were obtained for 97 patients. The postoperative median BKB score was 93% with a lower quartile score of 85% and an upper quartile score of 98%. Smaller numbers were available for post-CI City University of New York (CUNY) and Consonant-Nucleus-Consonant (CNC) word scores yet similar excellent results were seen. Conclusions: Our study results suggest the CI should be considered when BKB scores have dropped to 85%. We suggest that rather than LVAS cases representing a challenge to cochlear implantation, they are amongst the best candidates for surgery, and should receive a CI at an earlier stage in hearing loss, when they have better speech perception. This allows stable hearing to be established earlier along with excellent speech perception outcomes. Address correspondence and reprint requests to Catherine S. Birman, M.B.B.S., Ph.D., F.R.A.C.S., Sydney Cochlear Implant Centre, Building 39, Gladesville Hospital, Punt Road, Gladesville, NSW 2111, Australia; E-mail: medical.secretary@scic.org.au A.C.H. and B.K.K. were supported by a bursary provided by the Graham Fraser Memorial Fellowship to attend the Sydney Cochlear Implant Centre from the UK. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Hearing Improvement Following Middle Cranial Fossa Floor Defect Repair Utilizing a Modified Middle Fossa Approach and Reconstructive Techniques Background: Few studies report hearing preservation following middle cranial fossa (MCF) floor defect repair. Objective: To investigate audiological outcomes following MCF floor defect repair using a modified MCF suprapetrous approach. Study Design: Retrospective cohort. Setting: Tertiary referral center. Patients: Eleven patients, with MCF floor defects. Interventions: MCF floor defect surgical repairs with either fascia or fascia and bone graft. Main Outcome Measured: Hearing outcomes. Results: Eleven patients (two men) aged 34 to 82 years (median, 62 yrs) were identified. All patients were operated on by the same two senior surgeons (M.P. and M.G.). One patient with conductive hearing loss (based on tuning fork test) was excluded from the analysis due to missing preoperative audiogram data. All patients had middle fossa plate defects leading to cerebrospinal fluid (CSF) otorrhoea, rhinorrhoea, or meningitis. Nine patients had retrieval of herniated contents from the defect. Five patients had repair with temporalis fascia and split calvarial bone graft, and six patients had repair with fascia only. Follow up audiogram was performed at a mean 7.5 months (range, 0.5–24 mo). There was no recurrent CSF leak during the follow up period. The 10 patients (90.9%, 95% confidence interval [CI] 60.1–100.6) who had complete audiologic data sets demonstrated a mean improvement of 18.86 dB (range, –7.5 to 33.75 dB) in hearing postoperatively. One of these patients acquired a 7.5 dB reduction in postoperative hearing due to post-procedural middle ear effusion which subsequently resolved. Hearing improvement following fascial graft alone versus fascial graft with bone was 12.5 and 26.5 dB, respectively (p < 0.01). Conclusion: Middle fossa craniotomy with or without retrieval of herniated contents and floor reconstruction with fascia and bone is associated with improved hearing. Clinical efficacy of this technique, however, can be only fully established when a statistically meaningful number of cases have been performed. Address correspondence and reprint requests to Michael Gordon, M.B.B.S., F.R.A.C.S., Neurotology, Monash Health, 698 Glen Huntly Road, Caulfield South 3162, Australia; E-mail: michaelgordon@netspace.net.au Disclosure of Funding: None. The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Sensorineural Hearing Loss in the Nonimplanted Ear Following Cochlear Implantation in a Patient With Bilateral Enlarged Vestibular Aqueducts Objective: To document the case of a patient with bilateral enlarged vestibular aqueducts who experienced sensorineural hearing loss in the nonimplanted ear following unilateral cochlear implantation complicated by perilymph gusher requiring lumbar drain insertion and to highlight the need to counsel regarding the risk of potential hearing loss to the contralateral ear when preparing for cochlear implants in the setting of inner ear malformations. Patients: One patient with bilateral enlarged vestibular aqueducts in a tertiary referral center. Intervention(s): Cochlear implantation complicated by perilymph gusher requiring lumbar drain insertion. Main Outcome Measure(s): Bone conduction hearing thresholds, word recognition scores. Results: The patient underwent unilateral cochlear implantation, which was complicated by a perilymphatic gusher and necessitated placement of an intraoperative lumbar drain. On postoperative day 1, the patient reported hearing loss in the opposite ear. The word recognition score in the contralateral ear dropped from 24% at preimplantation to 8% at 2-weeks postimplantation, and did not improve at 6 months postimplantation. Moreover, the bone conduction threshold at 1 kHz worsened from 20 dB preoperatively to no response at 75 dB (the limit of the testing equipment) at 2-weeks postoperatively and only partially improved to 40 dB at 6 months postimplantation. Conclusion: As patients with inner ear malformations potentially have direct high-pressure anatomical connections between the perilymphatic spaces and the cerebrospinal fluid, they are at risk of hearing loss in the nonimplanted ear during cochlear implantation. This case highlights the need for potential additional patient counseling regarding this risk in the nonimplanted ear. Address correspondence and reprint requests to Yona Vaisbuch, M.D., Division of Otology and Neurotology, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, 2nd Floor, Stanford, CA 94305; E-mail: Yona@stanford.edu Y.V. and A.T. contributed equally to this article and are designated co-first authors. The author discloses no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Partial Epithelial–Mesenchymal Transition Was Observed Under p63 Expression in Acquired Middle Ear Cholesteatoma and Congenital Cholesteatoma Introduction: Partial epithelial–mesenchymal transition (p-EMT) is a process by which epithelial cells partially lose their intercellular adhesion and change to obtain migration ability. The transcription factor p63 regulates the expression of cadherin family and induces epithelial cell proliferation. In this study, we hypothesized that p-EMT under p63 expression may be a key factor in epithelial cell growth in middle ear cholesteatoma. Methods: Specimens were surgically excised from patients with congenital cholesteatoma (CC) (n = 48), acquired middle ear cholesteatoma (AC) (n = 120), and normal skin tissue (n = 34). We analyzed immunohistochemically for the EMT marker (N-cadherin), adherence junction marker (E-cadherin), and tight junction marker (claudin-1, claudin-4, occludin). We also examined the labeling index (LI) of p63 and Proliferating cell nuclear antigen (PCNA) (late S phase marker), and Snail expression as a mobility marker. Results: The expression of p63 (CC 51.0 ± 7.4%, AC 50.0 ± 5.9%) was significantly higher in the thickened epithelium of CC and AC compared with normal skin tissue (p < 0.0001). The loss of E-cadherin was observed (CC 50.0%, AC 55.8%) but the expression patterns in the tight junction were almost normal. N-cadherin was partially detected in the basal and upper layer of epithelium in CC and AC. In contrast to that of normal skin tissue, the LI of PCNA was significantly higher in AC (p < 0.0001). The positive rate of Snail was significantly higher in CC (p < 0.0001). Conclusion: This study indicates that p-EMT via the p63 signaling pathway might plays an essential role in epithelial growth in AC and CC formation, although tight junction formation and terminal differentiation were not affected in those processes. Address for correspondence and reprints requests: Tomomi Yamamoto-Fukuda, M.D., Ph.D., Department of Otorhinolaryngology, Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo 105-8461, Japan; E-mail: tomomiyf@jikei.ac.jp This study is supported by a Grant-in-Aid for Scientific Research from the Japanese Society for the Promotor of Science (JSPS) (no. 25462647 and JP16K11186 to T.Y.-F., and JP19K18786 to M.T.). The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Mycotic Pseudoaneurysm of Internal Carotid Artery Induced by Skull Base Osteomyelitis Background: Skull base osteomyelitis (SBO) is predominantly seen in immunocompromised patients, with diabetes mellitus being the most common underlying comorbidity. Microbial aetiology is commonly bacterial, although fungal SBO is encountered in a small fraction of patients. Treatment consists of prolonged antimicrobial therapy, control of underlying comorbidity, and surgical debridement in selected cases. Involvement of cranial nerves is a common complication and is considered a poor prognostic factor. Pseudoaneurysm of internal carotid artery caused by skull base osteomyelitis is a very rare complication, limited to few case reports only. Case: We report the case of a 55-year-old diabetic patient with bacterial SBO who developed pseudoaneurysm of cervical–petrous part of internal carotid artery during the course of treatment. Conclusion: New onset symptoms or persistent symptoms in SBO suggest progressive disease and necessitate re-evaluation of the microbial aetiology and antimicrobial treatment. Skull base osteomyelitis induced aneurysm is rare but can be life threatening, if not identified and managed immediately. Address correspondence and reprint requests to Prem Sagar, M.S., D.N.B., Assistant Professor, Department of Otorhinolaryngology and Head & Neck Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India; E-mail: sagardrprem@gmail.com The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Endoscopic Versus Microscopic Middle Ear Surgery: A Meta-analysis of Outcomes Following Tympanoplasty and Stapes Surgery Objective: This meta-analysis compares the efficacy and safety of endoscopic and microscopic approaches to tympanoplasty and stapes surgery, two common middle ear procedures. Data Sources: A comprehensive electronic search of PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library was conducted for studies published from the year 1960 through June 2018. Article selection and screening proceeded according to the strategies outlined in the standard Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Methods: Studies were assessed for quality using the Newcastle-Ottawa Scale and the Jadad scale depending on the presence of randomization. Bias was analyzed using funnel plots. For each outcome measure, a forest plot was generated and a pooled relative risk or risk difference was calculated to assess significance. Results: Twenty-one studies met the inclusion criteria, 16 tympanoplasty (1,323 ears) and 5 stapes surgery (283 ears). The nonrandomized studies scored moderately well but the randomized studies were of low quality with respect to the Newcastle-Ottawa Scale and the Jadad Scale, respectively. With respect to tympanoplasty, statistical analysis demonstrated that the endoscopic approach had significantly lower canalplasty rates, better cosmetic outcomes, and shorter operative times. Furthermore, endoscopic compared to microscopic methods were similar in terms of audiological outcome, graft success rate, and complication rate. Among stapes surgeries, the endoscopic approach demonstrated a significantly decreased incidence of postoperative pain and chorda tympani injury but was similar to the microscopic approach with respect to audiological outcome, postoperative dizziness, and operative time. Conclusions: Though the merits of endoscopic techniques are becoming more well known, there are still concerns regarding their efficacy and safety. An analysis of the current literature suggests that audiological, functional, and safety outcomes are similar, if not superior, for the endoscopic approach to both tympanoplasty and stapes surgery compared to the microscopic approach. With respect to tympanoplasty, patients undergoing the endoscopic approach had lower canalplasty rates, better cosmetic outcomes, and shorter operative times. Among stapes surgeries, patients in the endoscopic group had a lower incidence of postoperative pain and injury to the chorda tympani. This meta-analysis of the current evidence supports the use of endoscopic techniques for tympanoplasty and stapes surgery. Address correspondence and reprint requests to Vivian F. Kaul, M.D., Department of Otolaryngology—Head and Neck Surgery, One Gustave L Levy Place – Box 1189, New York, NY 10029; E-mail: vivian.zhu@mountsinai.org The authors disclose no conflicts of interest. Supplemental digital content is available in the text. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jcraniofacialsurgery.com). Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Quantitative Assessment of Inner Ear Histopathologic Findings in Partial Trisomy of 13 No abstract available

Treatment of Auricular Hematomas by OK-432: How and Why It Works Objectives: The aim of this article was to investigate the effectiveness and underlying mechanisms of OK-432 therapy in patients with auricular hematomas. Study Design and Setting: Case series with planned data collection. Subjects and Methods: We tried this therapy in 47 patients with auricular hematoma between April 2008 and August 2018. We aspirated as much of the fluid content of each lesion as possible with a 21-gage needle. We injected OK-432 solution into the lesion with the same needle that we used for aspiration. We performed this treatment at an outpatient basis without hospitalization. Results: Disappearance and marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the auricle did not occur in any patients. As adverse effects, local pain at the injection site and fever (37–38.5°C) were observed in some cases of the patients who had this therapy. The concentrations of various cytokines in each aspirate before and after OK-432 therapy were investigated. The production of tumor necrosis factor-α, interleukin-6, interleukin-8, interferon gamma, vascular endothelial growth factor, and periostin was significantly elevated in the aspirate fluid after OK-432 therapy. Conclusion: OK-432 therapy is simple, easy, safe, effective, and can be used as a substitute for surgery in the treatment of auricular hematoma. Address correspondence and reprint requests to Nobuo Ohta, M.D., Ph.D., Division of Otolaryngology, Tohoku Medical and Pharmaceutical University Hospital, 1-15-1, Fukumuro, Miyaginoku, Sendai 983-8536, Japan; E-mail: noohta@hosp.tohoku-mpu.ac.jp This study was supported by grants from the Ministry of Education, Science, Sports, and Culture, Japan. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Density of Macrophages Immunostained With Anti-Iba1 Antibody in the Vestibular Endorgans After Cochlear Implantation in the Human Hypothesis: Cochlear implantation may result in an increase in the density of macrophages in vestibular endorgans in the human. Background: Vestibular symptoms are a common complication of cochlear implantation. In a previous study, we demonstrated histological evidence of a foreign-body response caused by silicon and platinum in the human cochlea following cochlear implantation. The objective of the current study was to seek evidence of a possible immune response in vestibular endorgans after cochlear implantation. Methods: The density of macrophages immunostained with anti-Iba1 antibody in the vestibular endorgans (lateral and posterior semicircular canals, utricle and saccule) in 10 human subjects who had undergone unilateral cochlear implantation was studied by light microscopy. The densities of macrophages in the neuroepithelium, subepithelial stroma, and among dendritic processes in the mid-stromal zone in four vestibular endorgans in the implanted and the opposite unimplanted ears were compared. The distributions of macrophage morphology (amoeboid, transitional and ramified) were also compared. Results: The densities of macrophages in implanted ears in four vestibular endorgans were significantly greater than that in opposite unimplanted ears except in the subepithelial zone of the utricle and posterior semicircular canal. In contrast to the neuroepithelium, the subepithelial distribution of amoeboid macrophages in implanted ears was significantly less than in unimplanted ears. Conclusion: An increase in the density of macrophages in four vestibular endorgans after implantation was demonstrated. The transition among phenotype of macrophages suggested possible migration of amoeboid macrophages from the subepithelial stroma into the neuroepithelium. Address correspondence and reprint requests to Joseph B. Nadol Jr, M.D., Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114; E-mail: joseph_nadol@meei.harvard.edu This work was supported by grants #U24-DC013983 and R01-DC000152-34 from the National Institute of Deafness and Other Communication Disorders (NIDCD). The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Vestibular Schwannoma Tumor Size Is Associated With Acute Vestibular Symptoms After Gamma Knife Therapy Objective: To assess how pretreatment vestibular schwannoma (VS) tumor characteristics are associated with vestibular symptoms after gamma knife (GK) surgery. Study Design: Retrospective chart review of patients undergoing GK treatment for VS at our institution from 2005 to 2018. Setting: Academic tertiary referral center. Patients: Patients receiving primary GK surgery for vestibular schwannomas with at least 6 months of follow up. Patients with neurofibromatosis 2 or previous surgery were excluded. Main Outcome Measures: The presence of posttreatment vestibular symptoms within 6 months after GK. Clinical records were assessed for pretreatment tumor, patient, and treatment characteristics that impacted posttreatment symptoms. Results: All patients received radiation doses between 12 and 13 Gy. Of 115 patients, the average age was 60. Thirty-seven (32%) patients developed vestibular symptoms within 6 months post-GK, and 18 patients were referred for vestibular rehabilitation. Ten of 13 patients undergoing vestibular rehabilitation reported improvement. Overall, 112 patients had tumor measurements. Pretreatment tumors were significantly smaller for patients with acute vestibular symptoms (mean 1.43 cm versus 1.71 cm, p = 0.007). On multivariate analysis, smaller tumor size (p = 0.009, odds ratio [OR] = 0.29, 95% confidence interval [CI] [0.12–0.73]) was significantly associated with vestibular symptoms within 6 months of GK. Patients with tumors less than 1.6 cm were more likely to receive referrals for vestibular rehabilitation within 6 months posttreatment (25% versus 9.4%, p = 0.026, OR = 3.22, 95% CI [1.00, 11.32]). Conclusions: Smaller vestibular schwannomas were significantly associated with higher rates of post-GK vestibular symptoms. Pretreatment tumor size may be used to counsel patients on the likelihood of post-GK vestibular symptoms and vestibular rehabilitation. Address correspondence and reprint requests to Michael J. Ruckenstein, M.D., M.Sc., Department of Otorhinolaryngology, 3400 Civic Center Blvd, South Pavilion 3rd Floor, Philadelphia, PA 19104; E-mail: michael.ruckenstein@uphs.upenn.edu This work was not funded. Disclosures: J.A.B. is the owner of MobileOptx, LLC and was a consultant for TympBio. M.A.B. received honoraria from Varian. There are no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company