Kwang-Sun Lee

Establishment and characterization of nine new head and neck cancer cell lines

We established new cell lines from head and neck cancer patients for studies of adhesion molecules and cellular behavior in nine patients with primary or metastatic cancer treated at the Asan Medical Center. Explant cultures of fresh tumor tissue were used to develop new permanent tumor cell lines. Lines were tested for tumor formation and histology in nude mice. Flow cytometry and indirect immunofluorescence were used to assess DNA content and expression of the alpha 6, beta 4, and beta 1 integrin subunits and the intercellular adhesion molecule 1 (ICAM-1). In vitro growth patterns and adhesion to plastic were assessed using phase contrast microscopy. AMC-HN-1 to -8 were derived from patients with squamous cell carcinoma. AMC-HN-9 was from an undifferentiated carcinoma of the parotid gland. The 8 lines we tested produced nude mouse tumors that are identical to the histology of the original tumors. AMC-HN-1, -2, -5, and -9 have epithelioid or spindle cell morphology with poor cell-to-cell and cell-to-substrate adhesiveness. AMC-HN-3, -4, -7, and -8 grow as adherent epithelioid monolayers. AMC-HN-6 exhibits multilayer stratification. Four lines are near diploid, 4 are hyperdiploid and 1 is hypodiploid. Only three express ICAM-1. All lines express the alpha 6, beta 4, and beta 1 integrin subunits but to different extent. Four, AMC-HN-1, -2, -5, and -6, express the beta 4 integrin at low levels, AMC-HN-3, -4, -7, and -9, have intermediate beta 4 expression, and AMC-HN-8 has extremely high beta 4 expression. The AMC-HN cell lines are representative in vitro models for the study of head and neck cancer biology. Our preliminary results indicate a close relationship between integrin expression and cell adhesion in vitro.

Chlamydia pneumoniae infection enhances cellular proliferation and reduces steroid responsiveness of human peripheral blood mononuclear cells via a tumor necrosis factor-α-dependent pathway

Background Although epidemiological studies have found an association between Chlamydia pneumoniae infection and severe asthma, the causality and underlying mechanism are largely unknown. We hypothesized that C. pneumoniae infection increases the proliferation and enhances the survival of immune and inflammatory cells, resulting in reduced responsiveness to corticosteroids and suggesting that the underlying mechanism is related to a TNF‐α‐dependent pathway.

Proportion of bony cochlear nerve canal anomalies in unilateral sensorineural hearing loss in children

OBJECTIVE The aim of this study was to characterize the various bony anomalies of the inner ear in patients with unilateral sensorineural hearing loss using high-resolution temporal bone computed tomography and establish the relationship between hearing and the diameter of the bony cochlear nerve canal. METHODS We performed a retrospective review of 51 patients (mean age 11 years, range 0-20 years, 27 boys, 24 girls) who were diagnosed with unilateral sensorineural hearing loss with an audiogram. Coronal and axial diameter of the inner ear structures, including the internal auditory canal, bony cochlear nerve canal, and each turn of the cochlea and semicircular canals, were measured with high-resolution temporal bone computed tomography. The mean values (± 2 standard deviations) were calculated and compared between sensorineural hearing loss and normal ears, and between narrow bony cochlear nerve canal and normal bony cochlear nerve canal ears. Bony cochlear nerve canal atresia/stenosis was defined as a value less than 1.4mm in axial images. RESULTS The diameter of the bony cochlear nerve canal was significantly smaller in sensorineural hearing loss ears than in normal ears (p<.05). Associated inner ear anomalies, such as IAC stenosis (24%), cochlear hypoplasia (7-17%), and narrow semicircular canal bony island (8%) were only observed in the narrow bony cochlear nerve canal group. This group also showed statistically significant, severe to profound hearing loss compared to the normal bony cochlear nerve canal group (p<.05, R(2)=12.8%). CONCLUSIONS Most (57%) of the unilateral sensorineural hearing loss ears had bony cochlear nerve canal stenosis/atresia and this group showed associated inner ear anomalies. When the diameter of the bony cochlear nerve canal was less than 1.4mm, pure tone audio averages were more than 70 dB HL in most ears.

Clinical Manifestations and Risk Factors of Children Receiving Triple Ventilating Tube Insertions for Treatment of Recurrent Otitis Media With Effusion

OBJECTIVE. Our goal was to determine risk factors for children receiving additional ventilating tube insertions after initial tube insertion and to determine the changes of clinical manifestations in children who have undergone 3 ventilating tube insertion procedures. STUDY DESIGN. We retrospectively analyzed medical and operation records of 423 young patients who had ventilating tube insertion because of chronic otitis media with effusion from January 1993 to December 1998. The single-operation group included patients who had 1 ventilating tube insertion only, and the triple-operation group included patients who received ventilating tube insertion 3 times because of recurring chronic otitis media with effusion. RESULTS. At the first operation, there were significant differences between the single- and triple-operation groups in mean age, the proportion who received a concurrent adenoidectomy, the mean indwelling period of the first ventilating tube, the proportion who developed postoperative otorrhea within 1 month, and the proportion who had early extrusion of the ventilating tube within 3 months of surgery. In the triple-operation group, the accumulated number of adenoidectomies, the indwelling period of the ventilating tube, and the time interval before subsequent ventilating tube insertion after ventilating tube extrusion significantly increased as ventilating tube insertion procedures were performed repeatedly. Although there was no difference when compared with the single-operation group, the proportion of glue-like effusion significantly decreased as ventilating tube insertion procedures were performed repeatedly. There were no significant differences between the single- and triple-operation groups in male/female ratio, site of ventilating tube insertion, and the proportion of patients with glue-like effusion at the first ventilating tube insertion. CONCLUSIONS. The probability of receiving additional ventilating tube insertion because of recurrent otitis media with effusion significantly increased in younger patients at the time of first ventilating tube insertion. The concurrent adenoidectomy, duration of the ventilating tube, postoperative otorrhea within 1 month, and early extrusion of the ventilating tube also influenced the probability of additional ventilating tube insertion.

Outcomes of cochlear implantation in children with CHARGE syndrome

Abstract Conclusion: Regardless of the extent of inner ear anomalies and intellectual faculties, cochlear implantation (CI) with careful treatment planning can be a highly effective option for hearing rehabilitation in children with sensorineural hearing loss and CHARGE syndrome. Objective: CHARGE is a mnemonic term for coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, and ear anomalies. CHARGE syndrome is one of the leading causes of congenital deafness and blindness in children. We evaluated the language performance of six pediatric patients with CHARGE syndrome. Methods: Six patients with CHARGE syndrome underwent CI at the Asan Medical Center in Seoul between 2002 and 2012. The mean age of these CI patients was 4.9 years (range 2–9.8 years). All six patients had inner ear malformations; five children had an auricle anomaly and otitis media with effusion; three of these cases showed ossicle anomalies and four patients had downward displacement of the facial nerve (FN) toward the promontory; five patients showed delayed development; four of these children had cardiovascular malformations; three patients had cryptorchidism; two had choanal atresia; and there was one case of coloboma. Results: In the initial operations, two patients each were implanted with a CI512, CI24R, or CI24RE device. One patient initially received a CI512 device in the right ear, followed by a CI24RE device in the left ear. Another patient (case 1) first received a CI24R and then CI24RST device in the right ear due to poor performance, but this was eventually removed due to exposure of the electrode from adhesive otitis media and continuing poor performance. Assessment of the meaningful auditory integration scale (MAIS) showed that four patients reached a score above 95% and one patient achieved 60%. The categories of auditory performance (CAP) score showed that one patient reached CAP 7 at 2 years postoperatively and two cases showed CAP 5.5 at 1 year after implantation, while the remaining two patients had CAP scores of 3 at 12 months and 4.5 at 4 years, respectively. The speech intelligibility rating (SIR) score at 18 months post-surgery was 4.5 in two patients, 2.5 in two patients, and 1.5 in one case. The remaining patient (case 1) who was explanted showed no meaningful speech improvement.

Hearing improvement after cochlear implantation in common cavity malformed cochleae: long-term follow-up results

Abstract Conclusion: We suggest that cochlear implantation (CI) should be a good therapeutic modality for hearing restoration in patients with common cavity malformed ears. Objective: To analyze hearing improvement from CI performed in common cavity malformed cochleae. Methods: A total of 11 patients (5 male and 6 female, mean age 4.5 ± 2.8 years) and 12 ears were enrolled in this study. During the insertion of electrodes, we used C-arm fluoroscopy to avoid intrameatal placement. We evaluated hearing improvement every 6 months and the mean follow-up period was 80.5 ± 24.1 months (53–125 months). Results: During the operation, there were only four cases with fully inserted electrodes. Cerebrospinal fluid gushed out in two cases during the cochleostomy and postoperative meningitis occurred in two patients. One patient had to undergo reimplantation 4 years later due to device failure and recurrent meningitis. During the 48 months follow-up hearing evaluation, the ability of hearing increased along with the age. The final average MAIS, CAP, SIR, and open set one- and two-syllable word scores were 90.3 ± 18.1%, 4.9 ± 1.6, 3.1 ± 0.9, 24.1 ± 25.9%, and 48.6 ± 38.7%, respectively.

Complications following cochlear implantation in patients with anomalous inner ears: experiences in Asan Medical Center

Conclusion. Although the rate of postoperative complications was higher in patients with anomalous inner ears than in patients with normal inner ears, most were minor and could be managed conservatively. These findings suggest that cochlear implantation (CI) is safe even for patients with anomalous inner ears in experienced hospitals. Objective. To report complications encountered in patients with various types of anomalous inner ears undergoing CI in Asan Medical Center. Patients and methods. We retrospectively analyzed 388 patients who underwent CI between April 1999 and July 2006; of these, 80 patients had various inner ear anomalies. Immediate complications were defined as those occurring within 1 week of implantation and delayed complications as those occurring after 1 week. Minor and major complications were defined by severity requiring further management. Results. Of the 80 patients with anomalous inner ears, 20 cases (25.0%) had postoperative complications, including 5 (6.3%) with major complications: facial nerve palsy, recurrent meningitis, device failure, and cerebrospinal fluid (CSF) leakage. Re-implantations were performed in three patients (3.8%).

Facial nerve stimulation after cochlear implantation according to types of Nucleus 24-channel electrode arrays

Conclusion. In this study, we concluded that electrode design and location did not have a high level of influence on the prevalence of facial nerve stimulation (FNS) in normal cochleae. Objective. To analysis the prevalence of FNS after cochlear implantation with Nucleus 24-channel devices according to types of electrodes arrays. Patients and methods. We retrospectively analyzed medical and mapping records of 394 patients who received cochlear implants (CIs) manufactured by Cochlear Corporation from April 1999 to March 2007. Results. In all, 23 of 394 (5.8%) patients had FNS (CI24M 4 of 39 [10.3%], CI24RCS 9 of 192 [4.7%], CI24RST 9 of 21 [42.9%], and CI24RECA 1 of 87 [1.1%]). In addition, 4 of 324 (1.2%) patients with normal cochleae complained of FNS (CI24M 1 of 33 [3.0%], CI24RCS 2 of 173 [1.2%], and CI24RECA 1 of 71 [1.4%]). There was no difference between straight and perimodiolar electrode arrays in patients with normal cochleae. In addition, when comparing two types of Contour™ electrodes, Contour Advance™ (soft-tip) electrodes offered significantly lower incidence of FNS than Contour™ electrode arrays. We could manage these patients with methods such as decrease of C-level, selective channel turning off, and changes of mapping strategies.

Prevalence of radiologic superior canal dehiscence in normal ears and ears with chronic otitis media

Although labyrinth fistulae are caused mostly by cholesteatoma, they can occur in long‐standing chronic otitis media (COM) without cholesteatoma. We aimed to compare the prevalence of radiologic SCD on computed tomography (CT) between normal ears and contralateral COM ears in patients with unilateral COM and to assess the prevalence of superior canal dehiscence (SCD) according to the age.

Audiologic performance after cochlear implantation in children with X-linked deafness: comparison with deaf children with a normal inner ear structure.

Objective To compare audiologic performances of cochlear implantation (CI) in children with X-linked deafness with those of CI in age- and sex-matched children with normal cochleae. Patients We identified 4 patients with X-linked deafness and selected 10 age- and sex-matched deaf patients with normal cochleae between April 1999 and April 2012. Main Outcome Measures Auditory brainstem responses, Categories of Auditory Performance (CAP), and Meaningful Auditory Integration Scale (MAIS). Results The ages of patients with X-linked deafness at the time of implantation ranged between 1.3 and 13.6 years, with a mean age of 5.3 years. All patients were male subjects and showed severe-to-profound hearing loss. Patient 1 lacked ABR in both ears. Patients 2, 3, and 4 showed ABR in the contralateral ear, at 70, 70, and 90 dB nHL, respectively. All 4 patients had bilateral X-linked cochlear anomaly and experienced cerebrospinal fluid (CSF) gushers. Straight electrodes were used in Patients 1 and 3, with perimodiolar electrodes used in the others. Patients 2 and 3, who were about the same age, had CAP scores of 6 or more at 18 months after activation of the implant despite the use of different electrode arrays. There were no statistically significant differences in MAIS and CAP scores between each patient with X-linked deafness and the control group. Conclusion The audiologic performances of patient with X-linked deafness after CI are comparable to those of patients with normal inner ear structure after CI.