Mee Hyun Song

Mastoid and Epitympanic Obliteration in Canal Wall Up Mastoidectomy for Prevention of Retraction Pocket

Objective: To evaluate the surgical outcome in patients who have undergone mastoid and epitympanic obliteration technique. Study Design: Retrospective review. Setting: Tertiary care referral center. Patients: The study group included 151 patients with cholesteatoma who underwent mastoid and epitympanic obliteration technique. This technique was applied to cases who had a strong chance of recurrent retraction pocket and cholesteatoma formation, including those patients with an adhesive drum indicating poor eustachian tube function (n = 52) and patients with a destructive scutum (n = 68). Thirty-one patients had both an adhesive drum and a destructive scutum. Intervention: The connection between the mastoid cavity and the middle ear was blocked by obliterating the epitympanum and antrum with bone pate and the remaining mastoid cavity with abdominal fat. Main Outcome Measures: The postoperative drum state, the incidence of retraction pocket formation and cholesteatoma recurrence, the surgical complications of obliteration, and the hearing outcome. Results: In 114 of 151 patients (75.4%), the middle ear was well healed and well aerated. The retraction pocket formation or cholesteatoma recurrence did not develop in any subject. Postauricular skin depression was the most common complication of this technique (n = 31 [20.5%]). In three patients (2.0%), the bone pate used for obliteration was infected. Of the 56 cases who underwent a staged operation to regain their hearing, 37 resulted in a postoperative air-bone gap less than 20 dB hearing level. Conclusion: Mastoid and epitympanic obliteration is an effective option for preventing a retraction pocket and cholesteatoma recurrence in patients with a poorly functioning eustachian tube or a defective scutum, while preserving the same advantage of the canal wall up technique.

Chondrosarcoma of the Head and Neck

Chondrosarcoma of the head and neck region is a rare disease, representing approximately 0.1% of all head and neck neoplasms. The 5-year survival rate of chondrosarcoma is 70-80%, showing relatively good prognosis; however, it is known to progress slowly and eventually cause multiple metastases. In this study, we reviewed chondrosarcoma cases experienced at Yonsei University Medical College during the last 15 years to investigate its clinical characteristics and treatment outcome. The medical records of 8 patients who were diagnosed with chondrosarcoma of the head and neck region and underwent surgical treatment between December 1990 and December 2002 were retrospectively reviewed. The primary sites were sinus, mastoid, jugular foramen and thyroid cartilage. In all patients, the initial treatment modality was surgery, and postoperative radiation therapy was performed in 4 cases. The pathological findings showed chondrosarcoma in 7 cases and mesenchymal chondrosarcoma in 1 case. The treatment outcome resulted in 3 cases of recurrence, of which 2 cases were treated successfully and the other case expired of disease, indicating a survival rate of 87.5%. In the case that resulted in death, complete excision could not be achieved. Therefore, we concluded that wide excision is a beneficial initial treatment of this rare disease.

Effect of hypo-, iso- and hypertonic saline irrigation on secretory mucins and morphology of cultured human nasal epithelial cells

Conclusion. We speculate that isotonic saline is the most physiological irrigation solution in terms of mucus secretion and the cellular morphology of nasal epithelial cells. Objective. To determine the most physiologic and effective saline concentration for nasal irrigation in terms of mucus secretion and cellular morphology by using normal human nasal epithelial cells treated with hypo-, iso- and hypertonic saline. Material and methods. Fully differentiated passage-2 normal human nasal epithelial cells were treated with pure water and with 0.3% (hypotonic), 0.9% (isotonic) and 3% (hypertonic) saline solutions. mRNA expression levels of MUC5AC and MUC5B, which are known to be major airway mucins, were analyzed after 30 min using reverse transcriptase polymerase chain reaction. Total mucin and MUC5AC and MUC5B mucin secretions were analyzed using dot-blotting. Cellular morphology was observed with light microscopy after hematoxylin–eosin staining and with scanning electron microscopy. Results. MUC5AC and MUC5B mRNA levels did not change after treatment with pure water and various concentrations of saline. Total mucin and MUC5AC mucin secretions only increased following pure water treatment, while MUC5B mucin secretion increased with pure water, hypo- and hypertonic saline treatment. Morphologic analysis revealed that pure water severely damaged normal human nasal epithelial cells and that only isotonic saline did not affect their morphology.

Management of facial nerve schwannoma in patients with favorable facial function

Objective: We report six cases of facial nerve schwannomas in which surgical management allowed the preservation of facial nerve function. Specifically, this paper reports that a stripping surgery may provide favorable functional outcomes.

Jugular foramen schwannoma: analysis on its origin and location.

Objective: To examine the microsurgical anatomy of the jugular foramen and correlate anatomical findings to clinical manifestations of jugular foramen schwannomas concerning tumor origin and location. Study Design: Anatomical analysis of jugular foramen was performed by dissection of 25 cadavers (50 sides). By retrospective review of 9 cases of jugular foramen schwannomas surgically treated, the origin and location of tumor were studied. Setting: Tertiary referral center. Main Outcome Measures: The anatomical characteristics of jugular foramen, lower cranial nerves, and inferior petrosal sinus were correlated with the origin and growth pattern of jugular foramen schwannomas. Results: The superior and inferior ganglions of the glossopharyngeal nerve and the superior ganglion of the vagus nerve were located within the jugular foramen. The superior ganglions of the glossopharyngeal and vagus nerves were located superiorly, whereas the inferior ganglion of the glossopharyngeal nerve was found inferiorly in relation to the inferior petrosal sinus orifice. In our series of 9 cases of jugular foramen schwannoma, the most common nerve of origin was the vagus nerve, followed by the glossopharyngeal nerve. Conclusion: The reason for the predilection of the jugular foramen schwannoma for the glossopharyngeal and vagus nerves may be associated with the presence of their ganglions within the jugular foramen. Also, the inferior petrosal sinus may act as a barrier to tumor growth, and the location of the ganglion of tumor origination within the jugular foramen in relation to the inferior petrosal sinus may be correlated to the predominant direction of tumor extension.

Clinical and molecular characterizations of novel POU3F4 mutations reveal that DFN3 is due to null function of POU3F4 protein

X-linked deafness type 3 (DFN3), the most prevalent X-linked form of hereditary deafness, is caused by mutations in the POU3F4 locus, which encodes a member of the POU family of transcription factors. Despite numerous reports on clinical evaluations and genetic analyses describing novel POU3F4 mutations, little is known about how such mutations affect normal functions of the POU3F4 protein and cause inner ear malformations and deafness. Here we describe three novel mutations of the POU3F4 gene and their clinical characterizations in three Korean families carrying deafness segregating at the DFN3 locus. The three mutations cause a substitution (p.Arg329Pro) or a deletion (p.Ser310del) of highly conserved amino acid residues in the POU homeodomain or a truncation that eliminates both DNA-binding domains (p.Ala116fs). In an attempt to better understand the molecular mechanisms underlying their inner ear defects, we examined the behavior of the normal and mutant forms of the POU3F4 protein in C3H/10T1/2 mesodermal cells. Protein modeling as well as in vitro assays demonstrated that these mutations are detrimental to the tertiary structure of the POU3F4 protein and severely affect its ability to bind DNA. All three mutated POU3F4 proteins failed to transactivate expression of a reporter gene. In addition, all three failed to inhibit the transcriptional activity of wild-type proteins when both wild-type and mutant proteins were coexpressed. Since most of the mutations reported for DFN3 thus far are associated with regions that encode the DNA binding domains of POU3F4, our results strongly suggest that the deafness in DFN3 patients is largely due to the null function of POU3F4.

Clinical evaluation of DFN3 patients with deletions in the POU3F4 locus and detection of carrier female using MLPA

Song MH, Lee HK, Choi JY, Kim S, Bok J, Kim U‐K. Clinical evaluation of DFN3 patients with deletions in the POU3F4 locus and detection of carrier female using MLPA.

Correlation between genotype and phenotype in patients with bi-allelic SLC26A4 mutations

Mutation of SLC26A4 is the most common cause of prelingual hearing loss in East Asia. Patients with SLC26A4 mutations have variable phenotypes ranging from non‐syndromic hearing loss to Pendred syndrome. Here, we analyzed the correlation between genotype and various inner ear phenotypes and found a possible underlying mechanism. This study included 111 patients with bi‐allelic SLC26A4 mutations who had bilateral enlarged vestibular aqueduct (EVA) and hearing loss. p.H723R (61%), c.919‐2A>G (24%), and p.T410M (4%) were the most common mutations in Korean patients with EVAs. Residual hearing in patients with c.919‐2A>G or p.T410M mutations was better than that of patients with p.H723R homozygous mutations. Interestingly, quantitative polymerase chain reaction showed normal pendrin transcript (6–17% of normal levels) was produced from patients with c.919‐2A>G homozygous mutations. Surface expression ratio of pendrin and residual anion exchange activity were higher in cells transfected with p.T410M in comparison to cells transfected with p.H723R. These results suggest that there is a correlation between degree of residual hearing and the SLC26A4 genotype commonly found in the East Asian population.

ENaC- and CFTR-dependent ion and fluid transport in human middle ear epithelial cells

Ion channels, such as the epithelial sodium channel (ENaC), are essential for maintaining a fluid-free middle ear cavity by controlling periciliary fluid. Deviations from the normal volume or compositions of periciliary fluid are probably responsible for otitis media with effusion. To elucidate the physiologic roles of the ENaC and cystic fibrosis transmembrane conductance regulator (CFTR) in the middle ear mucosa, we compared the electrophysiological activity and protein expressions of ENaC and CFTR in normal human middle ear epithelial (NHMEE) cells with those in normal human nasal epithelial (NHNE) cells. We also evaluated the role of ENaC and CFTR in fluid transport by NHMEE cells. Short-circuit current (Isc) was measured in cell monolayers by modified Ussing chambers. Immunoblotting was performed for ENaC and CFTR. In addition, transepithelial fluid transport was measured after loading 100 microl of fluid onto the luminal cell surface. The amiloride-sensitive Isc in NHMEE cells was much larger than in NHNE cells, whereas the forskolin-induced Isc, presumably mediated by CFTR, was significantly smaller in NHMEE cells. ENaC subunits alpha, beta, and gamma were all detected in NHMEE cells, and their expressions were stronger than those in NHNE cells. In comparison, CFTR was also detected in the middle ear mucosa, but at a lower expression level than in NHNE cells. NHMEE cells showed more amiloride-sensitive fluid absorption than NHNE cells. In contrast, fluid absorption was less sensitive to forskolin/IBMX in NHMEE cells than in NHNE cells. The ATP induced Cl- efflux and the amplitude of ATP-induced current in NHMEE cells was much larger than in NHNE cells. In the present study, we have demonstrated an enhanced amiloride-sensitive Isc and fluid absorption in NHMEE cells, where the role of CFTR is limited. Our data also suggest that the ATP-induced Cl- channel could be an alternative Cl- channel to CFTR in NHMEE cells.

Mucosal melanoma arising in the eustachian tube

Mucosal melanoma is a very rare disease. Most cases have their origins in the head and neck region. To date,only three cases of melanoma originating from the eustachian tube have been reported. We present a case of mucosal melanoma of eustachian tube origin in which a complete excision was performed. In this case, the patient underwent adjuvant radiotherapy and the mass size greatly decreased, which aided subsequent surgical excision. Systemic chemotherapy was not utilized in this case; however, it is often used for palliative purposes. A literature review is also presented.