Chao-Yin Kuo

Hypoxia Induces a Metabolic Shift and Enhances the Stemness and Expansion of Cochlear Spiral Ganglion Stem/Progenitor Cells

Previously, we demonstrated that hypoxia (1% O2) enhances stemness markers and expands the cell numbers of cochlear stem/progenitor cells (SPCs). In this study, we further investigated the long-term effect of hypoxia on stemness and the bioenergetic status of cochlear spiral ganglion SPCs cultured at low oxygen tensions. Spiral ganglion SPCs were obtained from postnatal day 1 CBA/CaJ mouse pups. The measurement of oxygen consumption rate, extracellular acidification rate (ECAR), and intracellular adenosine triphosphate levels corresponding to 20% and 5% oxygen concentrations was determined using a Seahorse XF extracellular flux analyzer. After low oxygen tension cultivation for 21 days, the mean size of the hypoxia-expanded neurospheres was significantly increased at 5% O2; this correlated with high-level expression of hypoxia-inducible factor-1 alpha (Hif-1α), proliferating cell nuclear antigen (PCNA), cyclin D1, Abcg2, nestin, and Nanog proteins but downregulated expression of p27 compared to that in a normoxic condition. Low oxygen tension cultivation tended to increase the side population fraction, with a significant difference found at 5% O2 compared to that at 20% O2. In addition, hypoxia induced a metabolic energy shift of SPCs toward higher basal ECARs and higher maximum mitochondrial respiratory capacity but lower proton leak than under normoxia, where the SPC metabolism was switched toward glycolysis in long-term hypoxic cultivation.

Surgical Results of Retrograde Mastoidectomy with Primary Reconstruction of the Ear Canal and Mastoid Cavity

The aim of this study was to retrospectively review the long-term hearing results and the impact of mastoid exclusion/obliteration in patients with cholesteatoma (102 ears) who underwent retrograde tympanomastoidectomy and in whom bone chips/paté were applied as the sole materials during the procedure. In 79 ears, this was combined with ossiculoplasty in a single-stage procedure. In >71% of ears, the results of audiometric testing were monitored for more than 2 years. The results suggested there was a significant gain in hearing following surgery, with respect to the postoperative change in both air-conduction thresholds and air-bone gaps (P < 0.001). Linear regression analyses of pure-tone averages at different frequencies, before and after surgery, demonstrated that patients benefitted from a postoperative hearing gain at low and middle frequencies, but their hearing often deteriorated at frequencies of 8000 Hz. As for the impact of the type of tympanoplasty on hearing outcomes, type III-interposition markedly increased hearing gain. The overall rate of postoperative adverse events was 8.8%. We conclude that reconstruction of the ear canal and mastoid via mastoid exclusion/obliteration using bone chips/paté can be considered as an alternative procedure following retrograde mastoidectomy. It gives excellent surgical results and has fewer postoperative adverse events.

Effects of Microbubble Size on Ultrasound-Mediated Gene Transfection in Auditory Cells

Gene therapy for sensorineural hearing loss has recently been used to insert genes encoding functional proteins to preserve, protect, or even regenerate hair cells in the inner ear. Our previous study demonstrated a microbubble- (MB-)facilitated ultrasound (US) technique for delivering therapeutic medication to the inner ear. The present study investigated whether MB-US techniques help to enhance the efficiency of gene transfection by means of cationic liposomes on HEI-OC1 auditory cells and whether MBs of different sizes affect such efficiency. Our results demonstrated that the size of MBs was proportional to the concentration of albumin or dextrose. At a constant US power density, using 0.66, 1.32, and 2.83 μm albumin-shelled MBs increased the transfection rate as compared to the control by 30.6%, 54.1%, and 84.7%, respectively; likewise, using 1.39, 2.12, and 3.47 μm albumin-dextrose-shelled MBs increased the transfection rates by 15.9%, 34.3%, and 82.7%, respectively. The results indicate that MB-US is an effective technique to facilitate gene transfer on auditory cells in vitro. Such size-dependent MB oscillation behavior in the presence of US plays a role in enhancing gene transfer, and by manipulating the concentration of albumin or dextrose, MBs of different sizes can be produced.

Patulous Eustachian Tube Causing Hypermobile Eardrums

A 20-year-old man presented with a history of popping sounds in both ears during deep breathing. Audiometry showed normal hearing. Otoscopy revealed indrawn and severely atrophic eardrums that moved outward on nasal expiration and inward on inspiration, shown in a video.

Epidermal inclusion cyst of the soft palate and uvula in an infant

Congenital epidermal inclusion cysts of the soft palate or the uvula are uncommon mass lesions, and there have been only limited case reports of these in the literature. Although epidermal cysts are benign in nature and develop slowly, mass lesions growing near the soft palate or the uvula can result in velopharyngeal insufficiency, affecting both speech and swallowing. We present such a condition in a 7-month-old male infant with an epidermal inclusion cyst involving both the soft palate and the uvula.

Aberrant Facial Nerve Exposed behind the Eardrum

A 20-year-old man was referred to us with left-sided conductive hearing impairment since his childhood. Otoscopic examination revealed a stenotic meatus despite a normal-looking pinna. What impressed us was the pearly white bundle-like structure located directly behind the eardrum and next to the edge of the posterior canal wall (Figure 1). Accordingly, an exploratory tympanotomy was performed. Elevating the tympanomeatal flap to the end of the canal wall revealed a nerve-like bundle (Figure 2), which was confirmed to be the descending facial nerve by electrical stimulation monitoring. Because of concerns that the dehiscent facial nerve may be vulnerable, the patient was not eligible for further surgical intervention to correct his unilateral conductive hearing loss in such atresia condition. The Tri-Service General Hospital institutional review board deemed this report exempt from review because it is not a research study.

Changes in sinonasal mucosa in Wegener granulomatosis

A 63-year-old woman presented with a two-month history of intermittent epistaxis. In addition, she reported a sensation of fullness and progressive hearing loss in her left ear over the previous two weeks. Our differential diagnosis for these unexplained symptoms of the upper airway focused on

Diode Laser-assisted Excision of Glomus Tympanicum Tumor: Do Diode Lasers Help in Hemostasis and Tumor Removal?

This report focuses on the use of a diode laser on a 37-year-old woman with a glomus tympanicum tumor that completely filled her middle ear space. Through a postauricular approach, the exposed vascular tumor was gently coagulated to shrink it and sectioned to detach it from the middle ear using a diode laser, followed by the piecemeal removal of the tumor in toto. Ossicular reconstruction was performed in a single-stage tympano-ossiculoplasty. The patient had an uneventful postoperative course, and the audiometry revealed a complete closure of the air-bone gap one year after the operation. Due to its flexible delivery system that can sufficiently work in such restricted middle ear spaces, the application of the diode laser to treat the glomus tympanicum allowed adequate hemostasis to be achieved while avoiding subsequent sequelae. We demonstrate that the diode laser is a well applicable tool in treating highly vascular tumors of the middle ear like glomus tympanicum.

Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck Cancer

The use of cisplatin (CDDP), the most common chemotherapy drug for head and neck cancer, is limited by its undesirable side effects, especially nephrotoxicity. We investigated ultrasound microbubbles (USMB) as a tool to increase the local intra-tumoral CDDP level while decreasing systemic CDDP cytotoxicity. We allowed CDDP to interact with human serum albumin and then sonicated the resulting CDDP‒albumin complex to generate CDDP-loaded MBs (CDDP-MBs). We then established a head-and-neck tumor-bearing mouse model by implanting FaDu-fLuc/GFP cells into severe combined immunodeficiency mice and used IVIS® bioluminescence imaging to determine the tumor xenograft formation and size. Twice weekly (until Day 33), we administered CDDP only, CDDP + MBs + US, CDDP-MBs, or CDDP-MBs + US intravenously by tail-vein injection. The US treatment was administered at the tumor site immediately after injection. The in vivo systemic distribution of CDDP indicated that the kidney was the most vulnerable organ, followed by the liver, and then the inner ear. However, CDDP uptake into the kidney and liver was significantly decreased in both the CDDP-MBs and CDDP-MBs + US groups, suggesting that MB binding significantly reduced the systemic toxicity of CDDP. The CDDP-MBs + US treatment reduced the tumor size as effectively as conventional CDDP-only chemotherapy. Therefore, the combination of CDDP-MBs with ultrasound is effective and significantly attenuates CDDP-associated nephrotoxicity, indicating a promising clinical potential for this approach.

Video Nasoendoscopic-Assisted Transoral Adenoidectomy with the PEAK PlasmaBlade: A Preliminary Report of a Case Series

Objectives. The primary objective for this study is to evaluate the advantages, disadvantages, surgical applicability, and outcome of the pulsed electron avalanche knife (PEAK) PlasmaBlade in transoral adenoidectomy under direct visualization using video nasoendoscopy. Patients and Methods. In this series, six cases of adenoid hypertrophy showing varying clinical presentations in relation to its clinical course were surgically treated using a PEAK PlasmaBlade. Before and after surgery, all patients underwent nasal endoscopy to define the grading of hypertrophic adenoids and postoperative outcome. Pure tone audiometry and tympanometry tests were carried out to investigate the change in middle and inner ear functions. Results. The mean follow-up period was 23.8 months. Postoperatively, symptoms of otitis media with effusion were all relieved with closure of the air-bone gap (6/6). Other relevant ear complaints like tinnitus were resolved (1/1) and aural fullness disappeared in 87.5% of ears (7/8). Nasal obstruction (2/2) and postnasal drip (2/2) were improved after surgery. Conclusions. Based on this preliminary report of a case series in a limited sample size, we suggest that using the transoral PEAK PlasmaBlade for adenoidectomy guided by video nasoendoscopy is a safe and feasible surgical technique, allowing remarkable outcomes by providing precise tissue removal, effective hemostasis, and painless postoperative recovery.