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Objectives: To systematically review and evaluate metformin's potential impact on vestibular schwannoma (VS) growth., Data Sources: PubMed, Cochrane Library, and Embase., Review Methods: A retrospective cohort study was performed on sporadic VS patients undergoing initial observation who had at least two magnetic resonance imaging studies. Patients were stratified by metformin use during the observation period. Primary endpoint was VS growth, defined as at least a 2 mm increase in diameter. Survival free of tumor growth was evaluated between groups. Systematic review and meta-analysis were performed to produce a pooled odds ratio [OR]. Study heterogeneity was assessed and post-hoc power analysis was performed., Results: A total of 123 patients were included, of which 17% were taking metformin. Median patient age was 56.6 years (range, 25.1-84.5). There were no statistically significant differences between the groups. Survival analysis did not demonstrate a statistically significant difference in time to VS growth between groups (hazard ratio = 0.61, 95% confidence interval [CI] = 0.29-1.29). Furthermore, logistic regression analysis did not demonstrate a statistically significant difference between groups in the odds of VS growth (OR = 0.46, 95% CI = 0.17-1.27). Systematic review identified 3 studies. Meta-analysis suggested that metformin reduces the odds of developing VS growth (pooled OR = 0.45, 95% CI = 0.29-0.71). Studies demonstrated low between-study heterogeneity. Power analysis demonstrated a sample size of 220 patients with equal randomization would be required to prospectively identify a true difference with 80% power., Conclusions: Metformin use may reduce the odds of VS growth. A randomized trial would be ideal to identify an unbiased estimate of metformin's effect on VS growth. Laryngoscope, 133:2066-2072, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Disease involvement of specific locations may be more significant than simply the symptoms associated with that site; it is possible that involvement of certain sites could be associated with poor prognosis. We aimed to evaluate the outcomes of patients with MF with documented involvement of the EAC and external ear., Study Design: Retrospective analysis., Methods: We retrospectively reviewed 40 patients with MF that were treated by otologists between 2012 and 2021., Results: We report the largest series of patients with MF involving the external ear and EAC. Of the 40 patients included in this study, 17 presented with Mycosis Fungoides in the otologic region (MFO). Of these 17 MFO patients, 2/17 had involvement of the external ear only, 3/17 of the EAC only, 11/17 of both the external ear and EAC, and 1/17 of the periauricular skin. Of note, 11/14 (79%) patients presenting with EAC disease died compared to11/26 (42%) of patients without involvement. In addition, eight of the 13 (62%) patients with external ear involvement died compared to 14/27 (52%) of patients without involvement. Ear canal involvement was associated with a statistically significant shorter overall survival duration in patients with MF (p = 0.03). Furthermore, disease in the EAC was found to have a hazard ratio value of 2.565 (CI 1.102-5.970)., Conclusions: Involvement of the EAC by MF portends a poor prognosis. This finding highlights the need for a more in-depth otologic evaluation of patients with MF., Level of Evidence: 4 Laryngoscope, 133:1486-1491, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To report the largest single-institution review of temporal bone osteoradionecrosis (TBORN), and characterize the disease's natural history, prognostic factors, management, and outcomes., Study Design: Retrospective chart review., Methods: Retrospective review was conducted to identify patients with TBORN. Pertinent data were extracted. Descriptive statistics were used to summarize patient, tumor, and treatment characteristics. Multivariable analyses were conducted to explore associations between these characteristics and time to TBORN diagnosis and risk of developing diffuse disease., Results: TBORN was identified in 145 temporal bones from 128 patients. Mean age at diagnosis was 62 years, and mean time to diagnosis after radiotherapy was 10 years. Age greater than 50 years was associated with earlier diagnosis. According to the Ramsden criteria, 76% of TBs had localized and 24% had diffuse disease at initial diagnosis; 37% had diffuse disease at last follow-up. On multivariable analysis, diabetes, three-dimensional conformal radiotherapy (3D-CRT), and periauricular skin malignancy were significant risk factors for developing diffuse disease. Localized disease was successfully managed with conservative measures, whereas surgery was often necessary for diffuse disease. When TBORN spread outside the mastoid or infratemporal fossa, conservative measures were always unsuccessful., Conclusions: TBORN occurs earlier in older patients. While diffuse disease is less common than localized disease, it occurs more frequently in patients with diabetes, history of 3D-CRT, and periauricular skin malignancies. Conservative management is appropriate for localized disease, while surgery is often necessary for diffuse disease. The prognostic factors identified helped propose a TBORN staging system and treatment guidelines which may improve patient risk stratification and disease management., Level of Evidence: 4 Laryngoscope, 131:2578-2585, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Examine the presentation and management characteristics of seven patients with melanoma of the external auditory canal (EAC)., Study Design: Retrospective case series and review of the relevant literature., Methods: Records of seven patients from 2003 to 2017 with melanoma of the EAC were reviewed for characteristics of presentation, subsequent management, and outcomes. A thorough review of relevant literature is presented., Results: The median age is 52 years, with four females. The average Breslow depth was 3.6 mm, with five patients having a Clark level IV or greater on presentation. Six patients underwent lateral temporal bone resection, and one patient underwent wide local excision of the cartilaginous canal. Sentinel lymph node biopsy (SLNB) was performed in three patients. Three patients experienced distant recurrence an average of 20 months following primary therapy. Median follow-up was 21 months. At last follow-up, four were free of disease, one had active disease, and two were deceased from melanoma., Conclusions: This is the largest series and the first to report the use of SLNB for patients with EAC melanoma in the peer-reviewed literature. Patients with external auditory canal melanoma present with higher Breslow thickness and stage relative to all external ear melanomas. Management should include wide local excision, which entails lateral temporal bone resection when the bony ear canal is involved. SLNB has a critical role in identifying patients with early metastatic disease. Postoperative radiation therapy should be considered for patients with high-risk features to reduce the risk of locoregional relapse. Chemotherapy, and especially immunotherapy, has an emerging role for this disease., Level of Evidence: 4 Laryngoscope, 131:165-172, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To compare the complication rate for osseointegrated hearing aids (OIHA) in patients with or without irradiation., Study Design: Retrospective case review., Methods: We studied patients with OIHAs implanted between January 1, 2005, and July 15, 2013 in a tertiary university center with a referral otology and neurotology practice. Demographics, history of oncologic surgery, follow-up length after OIHA implantation, radiation history and dosage, postoperative complications, and chronologic relationship between oncologic resection, OIHA implantation, and irradiation were reviewed to collect information. Soft tissue complications were graded according to a modified Holgers classification., Results: The study included 48 patients. Twenty-nine patients (32 implants) did not undergo radiotherapy and 19 patients (19 implants) did. In the radiotherapy group, six patients had OIHAs implanted before radiotherapy, and 13 had OIHAs implanted in irradiated bone. Of these 13 patients, one had OIHA implanted during primary oncologic surgery; 11 had OIHA implanted during secondary surgery; and one patient did not have oncologic surgery. Patients with both OIHA implantation and radiotherapy had more complications than patients without radiotherapy (31.6% vs. 24.1%, P > 0.05) and more major complications than patients without radiotherapy (26.3% vs. 3.4%, P > 0.05). Patients with OIHAs implanted before radiotherapy did not have any complications. There were significantly fewer and less severe complications in patients with OIHAs implanted during primary oncologic resection than in patients with OIHAs implanted secondarily (0/8 vs. 8/11, P < 0.05)., Conclusions: The rate and severity of complications of OIHAs can be minimized by implanting the device before irradiation, ideally at the time of primary oncologic surgery., Level of Evidence: 4. Laryngoscope, 126:1187-1192, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: There is no approved agent to prevent cisplatin-induced ototoxicity. Our objectives were to: 1) identify and compare the effect of intratympanic injections of lactate or N-acetylcysteine (NAC) in the prevention of cisplatin-induced ototoxicity, 2) investigate inner ear protection using a scanning electron microscope, and 3) study systemic diffusion of intratympanic NAC., Study Design: Prospective animal study., Methods: Sixteen guinea pigs formed two groups, and respectively received intratympanic lactate and 20% NAC in one ear. The contralateral ears received a control saline solution. After 30 minutes, an intraperitoneal cisplatin injection of 3 mg/kg was performed and repeated eight times, once a week, to achieve 24 mg/kg. Auditory brainstem responses (ABRs) were recorded before any injection, after 9 mg/kg and after 24 mg/kg of cisplatin for the frequencies 2, 4, 6 and 8 kHz. Cochleas were analyzed under scanning electron microscope. Systemic diffusion of NAC was studied using high-performance liquid chromatography., Results: For the control ears, ABR thresholds increased uniformly and averaged 28.4 dB. The lactate group showed a lower threshold increase and averaged 17.0 dB. The NAC showed an important threshold increase of 89.0 dB. Lactate showed a significant hearing protection at 2000 Hz (P < .01). Electron microscopy revealed partial preservation of outer hair cell stereocilia for the ears treated with lactate and severe disruption for NAC group. No systemic diffusion of NAC was observed with chromatography., Conclusions: Intratympanic lactate offers significant partial protection against cisplatin-induced ototoxicity at midfrequencies. High-concentration NAC does not seem a viable solution as it causes a considerable inflammatory reaction. NAC does not diffuse systemically.