Ken Kitamura

Tokyo Medical and Dental University, Edo, Tōkyō, Japan

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Publications (132)176.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, it has become clear that HPV affects the development of head and neck cancer, particularly oropharyngeal squamous cell carcinoma (OPSCC). HPV-related OPSCCs are reported to be frequently observed among patients with a relatively younger age and those without smoking habits, and also to show a relatively better prognosis compared with OPSCC patients without HPV infection. In the United States, the incidence of HPV-related OPSCC has been increasing in association with the diversification of sexual activity among young individuals. Similarly, the incidence of HPV-related carcinomas has been increasing in Japan. For instance, uterine cervical cancers have been increasing among younger females, and the incidence of OPSCC has also been gradually increasing in spite of a decreasing trend in smoking habits and alcohol consumption. However, there have been only a few Japanese studies that have examined the incidence and prognostic significance of HPV infection in terms of its impact on the outcomes of OPSCC. Therefore, further analyses are needed to establish an appropriate treatment strategy for Japanese OPSCC patients. The aim of this study was to elucidate the frequency and clinical implications of the HPV infection status in Japanese OPSCC, using both a sequencing analysis and IHC.
    Acta Oto-Laryngologica 07/2014; · 1.11 Impact Factor
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    ABSTRACT: Micro-computed tomography (micro-CT) is useful for assessing the 3-dimensional (3D) morphology and age-related changes of the otoconial layer.
    Ontology & Neurotology 06/2014; · 2.01 Impact Factor
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    ABSTRACT: Abstract Conclusion: The long-term follow-up study revealed a good audiovestibular prognosis in our patients with Vogt-Koyanagi-Harada disease (VKH) after adequate treatment. Objectives: To evaluate the audiovestibular findings and long-term prognosis of patients with VKH. Methods: A total of 82 ears in 41 patients (9 males and 32 females, aged 18-78 years) with VKH were examined in the audiovestibular study. Of the 41 patients, 16 patients with follow-up periods of more than 12 months (13-158 months) were included in the long-term follow-up study. Audiovestibular examinations included pure-tone audiometry; positional, positioning, and spontaneous nystagmus tests; and a caloric test. Results: Among the 41 patients, 28 (68%) complained of auditory symptoms at the initial visit and 28 (68%) showed sensorineural hearing loss (SNHL). Of the 24 patients who underwent nystagmus tests, only 3 (13%) presented with vestibular symptoms whereas 11 (46%) had nystagmus. Among 32 ears in 16 patients enrolled in the long-term follow-up study, 19 ears showed SNHL at the initial visit. The SNHL returned to normal in 14 ears (74%) and remained minimal in severity in the other 5 ears (26%) at the last visit. None of the patients showed persistent or repetitive vestibular symptoms.
    Acta oto-laryngologica 04/2014; 134(4):339-44. · 0.98 Impact Factor
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    ABSTRACT: Mutations in DFNA5 lead to autosomal dominant nonsyndromic hereditary hearing loss (NSHHL). To date, four different mutations in DFNA5 have been reported to cause hearing loss. A 3 bp deletion mutation (c.991-15_991-13del) was identified in Chinese and Korean families with autosomal dominant NSHHL, which suggested that the 3 bp deletion mutation was derived from a single origin. In the present study, we performed genetic screening of mutations in the interval between intron 6 and exon 9 of DFNA5 in 65 Japanese patients with autosomal dominant NSHHL and identified the c.991-15_991-13del mutation in two patients. Furthermore, we compared the DFNA5-linked haplotypes consisting of intragenic SNPs between the reported Chinese and Korean families and found that the Japanese patients showed a shared region spanning 41,874 bp. This is the first report of DFNA5 mutations in Japanese patients with autosomal dominant NSHHL, supporting the suggestion that the 3 bp deletion mutation occurred in their ancestors.
    Annals of Human Genetics 02/2014; · 2.22 Impact Factor
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    ABSTRACT: OBJECTIVE: Molecular analysis using archival human inner ear specimens is challenging because of the anatomical complexity, long-term fixation, and decalcification. However, this method may provide great benefit for elucidation of otological diseases. Here, we extracted mRNA for RT-PCR from tissues dissected from archival FFPE human inner ears by laser microdissection. METHODS: Three human temporal bones obtained at autopsy were fixed in formalin, decalcified by EDTA, and embedded in paraffin. The samples were isolated into spiral ligaments, outer hair cells, spiral ganglion cells, and stria vascularis by laser microdissection. RNA was extracted and heat-treated in 10 mM citrate buffer to remove the formalin-derived modification. To identify the sites where COCH and SLC26A5 mRNA were expressed, semi-nested RT-PCR was performed. We also examined how long COCH mRNA could be amplified by semi-nested RT-PCR in archival temporal bone. RESULTS: COCH was expressed in the spiral ligament and stria vascularis. However, SLC26A5 was expressed only in outer hair cells. The maximum base length of COCH mRNA amplified by RT-PCR was 98 bp in 1 case and 123 bp in 2 cases. CONCLUSION: We detected COCH and SLC26A5 mRNA in specific structures and cells of the inner ear from archival human temporal bone. Our innovative method using laser microdissection and semi-nested RT-PCR should advance future RNA study of human inner ear diseases.
    Hearing research 05/2013; · 2.85 Impact Factor
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    ABSTRACT: Hearing loss (HL) is the most common sensory disorder in humans. Many patients with mitochondrial diseases have sensorineural HL (SNHL). The HL of these patients manifests as a consequence of either syndromic or nonsyndromic mitochondrial diseases. Furthermore, the phenotypes vary among patients even if they are carrying the same mutation. Therefore, these features make it necessary to analyze every presumed mutation in patients with hereditary HL, but the extensive analysis of various mutations is laborious. We analyzed 373 patients with suspected hereditary HL by using an extended suspension-array screening system for major mitochondrial DNA (mtDNA) mutations, which can detect 32 other mtDNA mutations in addition to the previously analyzed 29 mutations. In the present study, we detected 2 different mtDNA mutations among these 373 patients; m.7444G>A in the MT-CO1 gene and m.7472insC in the MT-TS1 gene in 1 patient (0.3%) for each. As these two patients had no clinical features other than HL, they had not been suspected of having mtDNA mutations. This extended screening system together with the previous one is useful for the genetic diagnosis and epidemiological study of both syndromic and nonsyndromic HL.Journal of Human Genetics advance online publication, 13 September 2012; doi:10.1038/jhg.2012.109.
    Journal of Human Genetics 09/2012; · 2.53 Impact Factor
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    ABSTRACT: When we assess anatomical problems and the safety and effectiveness for performing a difficult surgical procedure or planning novel surgical approaches, preoperative human dissections are very helpful. However, embalming with the conventional formaldehyde method makes the soft tissue of the cadaver harder than that of a living body. Therefore, the cadaver embalmed with conventional formaldehyde is not appropriate for dissections when assess surgical approaches. Thiel's method is a novel embalming technique, first reported by W. Theil in 1992. This method can preserve color and softness of the cadaver without risk of infections. We have used cadavers embalmed with Thiel's method for preoperative assessments and have confirmed the usefulness of this method especially for the prevention of complications or in assessing surgical approaches. The cadaver embalmed with this method has several advantages over other embalming methods and it might be also useful for the developments of new surgical devices or evaluation of a surgeon's skill.
    Nippon Jibiinkoka Gakkai Kaiho 08/2012; 115(8):791-4.
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    ABSTRACT: Abstract Conclusion: Haplogroup D4b, especially subhaplogroup D4b2, may be one of the modifiers associated with the phenotypic expression of hereditary hearing loss (HL). Objectives: The present study investigated the association between suspected hereditary HL and 12 major mtDNA haplogroups in a Japanese population. Besides the mutations of mitochondrial DNA, many modifiers including environmental factors and genetic polymorphisms are involved in HL. Methods: The subjects comprised 373 unrelated Japanese patients with suspected hereditary HL and 480 controls. Twenty of the 373 patients were excluded from the study because the m.1555A>G or the m.3243A>G mutation had been detected in them. The mitochondrial haplotypes were classified into 12 major Japanese haplogroups (i.e. F, B, A, N9a, N9b, M7a, M7b, G1, G2, D4a, D4b, and D5). The frequency of each haplogroup in patients with HL was compared with that of the controls using the chi-squared test. Results: The frequency of the HL patients carrying the mitochondrial haplogroup D4b was significantly higher than that of the controls (37/353 [10.5%] vs 31/480 [6.5%]; OR 1.70 [95% CI 1.03-2.79, p = 0.036]) and evidence for enhancement was found in subhaplogroup D4b2 (32/353 [9.1%] vs 24/480 [5%], OR 1.89 [95% CI 1.09-3.28, p = 0.021]).
    Acta oto-laryngologica 07/2012; 132(11):1178-82. · 0.98 Impact Factor
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    ABSTRACT: Intralabyrinthine schwannomas (ILSs) are rare benign neoplasms arising from distal branches of the cochlear, superior vestibular, or inferior vestibular nerves. We report on a case of ILS with extensions to the round window niche and internal auditory canal (IAC) in a 47-year-old male. The patient noticed sudden hearing loss and tinnitus in his left ear at the age of 36, received steroid therapies, but was left with complete deafness. He had suffered from repetitive vertigo attacks for 6 months at 41. At 46 when he presented with deterioration of his left tinnitus, he was finally diagnosed as having ILS on enhanced MRI and constructive interference in steady-state analysis. The tumor was located in all turns of cochlea, vestibule, and the fundus of the IAC. Because follow-up MRI suggested growth of the IAC tumor, we performed total removal of the tumor via the translabyrinthine and transcanal approaches. The tumor had invaded only the cochlear nerve in the IAC and appeared in the round window niche in the middle ear. Pathological examination showed an Antoni A type schwannoma with fibrous changes of the semicircular canals. We should remember this inner
    Nippon Jibiinkoka Gakkai Kaiho 07/2012; 115(7):687-92.
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    ABSTRACT: We report on the case of a 51-year-old woman who presented with refractory pharyngitis caused by toxigenic Corynebacteriumn ulcerans (C. ulcerans). Thick pseudomembrane formations and yellowish pus were observed in her nasopharynx. Based on her clinical course and history of breeding cats, we considered C. ulcerans infection as the possible diagnosis. She was treated with macrolide administration and her symptoms immediately improved. C. ulcerans was identified in pus from the patient's pharynx as well as in discharge material from her cat's eyes, and C. ulcerans was thought to have caused her pharyngitis. C. ulcerans is one of the infecting bacteria which can cause a zoonotic infection. In Japan, some cases with C. ulcerans infection from cats have been reported. It is important that we should consider C. ulcerans infection as a differential diagnosis of refractory pharyngitis.
    Nippon Jibiinkoka Gakkai Kaiho 07/2012; 115(7):682-6.
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    ABSTRACT: Different from adults, the superior semicircular canal (SSC) protrudes into the cranium during the fetal period. This might cause adhesion of the membranous labyrinth to dura as the bony labyrinth develops much later than the membranous labyrinth. This adhesion interferes with ossification and leads to a bony defect in the SSC. The purpose of this study was to investigate a possible etiology of superior canal dehiscence syndrome (SCDS) from a view point of ontogeny. Forty-two adult cadavers and 4 fetal cadavers were used for macroscopic observation of the middle cranial fossa (MCF). In addition, six fetuses underwent computed tomography (CT) examinations. The volume data of the CT obtained from four adults were also used for comparison. Using these CT data, we investigated the anatomic relationship between the MCF and SSC. The SSC and the cochlea in fetuses protruded into the cranium in macroscopic anatomy and CT examination. On the other hand, the SSC of all adults was completely or mostly buried in the temporal bone.
    Acta oto-laryngologica 12/2011; 132(4):385-90. · 0.98 Impact Factor
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    ABSTRACT: A final incidence of bilateral involvement was 20.7%. Episodic spells of vertigo were completely controlled in 23 of 29 patients, while 11 of 29 patients demonstrated over 70 dB hearing loss. To analyze the clinical course of 29 patients with Meniere's disease during follow-up of 10 years or more. The subjects were 29 patients with a mean follow-up of 18.3 years. The hearing level was measured by the pure tone average (PTA) of four frequencies at the initial and the final examination, and it was classified into four categories according to the American Academy of Otolaryngology-Head and Neck Society (AAO-HNS) criteria. The control of vertigo was evaluated by the modified AAO-HNS criteria. At enrolment two patients had bilateral involvement. In the period of follow-up, bilateral involvement emerged in four more patients. The hearing levels at the final examinations were as follows: 3 patients, <25 dB; 6 patients, 26-40 dB; 9 patients, 41-70 dB; and 11 patients, >70 dB. The control of vertigo according to the modified AAO-HNS guideline was class A in 23 patients, class B in 2 patients, and class C in 1 patient; the remaining 3 patients could not be evaluated.
    Acta oto-laryngologica 11/2011; 132(1):10-5. · 0.98 Impact Factor
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    ABSTRACT: The effectiveness of bone anchored hearing aid (BAHA) for the patients with congenital aural atresia was evaluated by multicenter clinical study in Japan. Twenty patients (17 bilateral and 3 hemilateral) of congenital auricular atresia were registered for this study and finally, 18 of them (15 bilateral and 3 unilateral) were subjected to further evaluation. Primary endpoint of this study was free sound-field pure-tone audiometory and speech threshold hearing test in quiet and noisy circumstances. Secondary endpoint of this study was patient's satisfaction based upon APHAB (Abbreviated Profile of Hearing Aid Benefit) questionnaire survey. These results were compared between before and 12 weeks after BAHA surgery. Both hearing level of pure tone and speech threshold significantly improved after BAHA surgery. APHAB scores also suggested the improvement of the QOL after BAHA usage, except for the scores that concerned with unpleasantness of noisy sound. BAHA is one of the useful options for the treatment of congenital auricular atresia.
    Nippon Jibiinkoka Gakkai Kaiho 09/2011; 114(9):761-7.
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    ABSTRACT: The bone-anchored hearing aid (BAHA) has advantages over conventional hearing aids in sound quality and speech reception in silence, but requires surgery and may have peri-and postoperative complications. We evaluated audiological findings and complications in 12 subjects (13 ears)-8 men and 4 women aged 20-71--undergoing BAHA surgery from September 2001 to October 2005. Surgery was for single-sided deafness in one subject. Mean warble tone thresholds with BAHA were 29.9dB and 65.2dB without. Functional gains ranged from 16 to 52dB (mean: 35.3dB). Dural exposure or venous hemorrhage was seen in 4 ears, and mastoid cells opened and a skin flap was damaged in 1 ear each. No severe complications occurred perioperatively. Skin reactions categorized into grade 1 or more were recognized in nearly 70% of ears during the first postoperative year but most were a grade 1 reaction and skin reactions decreased with time. Skin overgrowth occurred in 1 ear immediately after an abutment separated accidentally from the fixture. All complications were treated in outpatient clinics. No fixture extrusion occurred. The decision to proceed with BAHA surgery thus required fully informed consent based on knowledge of peri-and postoperative complications.
    Nippon Jibiinkoka Gakkai Kaiho 07/2011; 114(7):607-14.
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    ABSTRACT: A reported mutation in SIX1 was identified in a patient with familial hearing loss (HL), a left preauricular pit, and bilateral enlarged vestibular aqueducts (EVA). Although the characteristic symptoms of EVA including fluctuating HL and repetitive vertigo were not seen in the patient, further studies are needed to clarify the association between EVA and such symptoms. To study the audiovestibular functions, and to identify the causative gene in a patient with branchio-oto syndrome. We enrolled a 30-year-old female in whom HL was pointed out at the age of 6 years. She visited our department at the age of 21 years, and had not experienced any progression of her HL, tinnitus, or vertigo. Pure-tone audiograms showed bilateral moderate mixed HL with no apparent progression during a 9-year follow-up period. Audiovestibular examinations included distortion product otoacoustic emissions (DPOAEs), electrocochleography (ECochG), and electronystagmography (ENG). Direct sequencing was utilized to screen for SIX1, EYA1, SLC26A4, GJB2, and mitochondrial DNA MTRNR1 including 1555 position. The findings of DPOAEs, ECochG, and ENG indicated cochlear HL with no vestibular dysfunction. A previously reported mutation of a heterozygous c.386A > G (p.Y129C) in SIX1 was detected. No mutation was identified in EYA1, SLC26A4, GJB2, or MTRNR1.
    Acta oto-laryngologica 01/2011; 131(4):413-8. · 0.98 Impact Factor
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    ABSTRACT: A modified paraffin-embedding method could be applied to histopathological and immunohistochemical studies of the human cochlea. The complementary use of molecular and immunohistochemical techniques by means of this method is thus considered to be a valuable tool for the future study of the human inner ear. To propose a new paraffin-embedding method for the morphological and immunohistochemical study of the human cochlea. Five human temporal bones were harvested at autopsy. The temporal bone specimens were fixed in 20% buffered formalin, decalcified with EDTA, cropped to a cube of approximately 15 mm, embedded in paraffin, and then cut into 6 microm thick sections. The sections were stained with hematoxylin and eosin, and immunostained with anti-prestin and anti-neurofilament antibodies. Although paraffin-embedded sections cannot show the excellent morphology of the delicate membranous labyrinth obtained with celloidin, this technique successfully preserved the morphology of the cochlea, especially the organ of Corti, thereby enabling us to obtain excellent immunostaining results.
    Acta oto-laryngologica 07/2010; 130(7):788-92. · 0.98 Impact Factor
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    ABSTRACT: This study investigated the efficacy of hyperbaric oxygen therapy (HBOT) as a secondary treatment for patients with idiopathic sudden sensorineural hearing loss (ISSNHL) in the subacute and chronic phases. Forty-eight ISSNHL patients (HBOT group) who had received primary conventional treatment within 4 weeks after onset and underwent HBOT between 4 and 20 weeks post-onset were retrospectively compared with 44 ISSNHL patients (control group) with primary conventional treatment alone. Mean hearing gain was slight, with gains of 5.2 +/- 8.9 dB in the HBOT group and 2.0 +/- 7.6 dB in the control group. However, no significant difference was recognized between the two groups. In the HBOT group, no significant difference was observed in hearing gain among patients with HBOT initial time at 4-7, 8-11, 12-15 or 16-20 weeks after onset. Meanwhile, hearing gain was significantly higher in patients with profound hearing loss than in the other patients. We conclude that the effectiveness of secondary HBOT for ISSNHL patients in either subacute or chronic phase remains unproven, and thus, the decision administer HBOT should be made with caution.
    Journal of medical and dental sciences 06/2010; 57(2):127-32.
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    ABSTRACT: We report a 24-month-follow-up study of argon plasma coagulation of the inferior turbinate (APC) in patients with perennial nasal allergy. This was a retrospective study, in which 41 patients with perennial allergic rhinitis were treated by inferior turbinate reduction using APC. The grades of nasal stuffiness, rhinorrhea, sneezing and the daily activity impairment caused by these nasal symptoms were evaluated before and then 6, 9, 12, 15, 18, 21, and 24 months after APC, using a questionnaire graded on a four-point scale according to the Severity Criteria of Symptoms of Nasal Allergy issued by the Japanese Society of Allergology. Both nasal stuffiness and any daily activity impairment significantly improved 6 months after APC. Twenty four months after APC, 8/10 (80%) of the patients reported mild or no stuffiness and 9/10 (90%) of the patients reported mild or no daily activity impairement. Neither rhinorrhea nor sneezing were significantly improved during this study. Of the 41 patients 18 (43.9%) received no additional treatment. A second APC treatment was administered to 10/41 (24.4%) patients during follow-up period. Additional conservative medications were needed in 15/41 (36.6%) patients. Among the patients uncontrolled by conservative medical treatment, inferior turbinate reduction using APC provides significant relief in a 24-month-follow-up from nasal stuffiness and daily activity impairment.
    Journal of medical and dental sciences 03/2010; 57(1):11-5.
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    ABSTRACT: Sensorineural hearing loss (HL) is one of the most frequent clinical features in patients with mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations, and hearing is impaired in over half of all cases with mitochondrial disorders. This study analyzed 373 patients with suspected hereditary HL using an extensive and rapid suspension-array screening system for 29 major mtDNA mutations, including the m.1555A>G homoplasmic mutation in the MT-RNR1 gene, which causes non-syndromic sensorineural HL and aminoglycoside-induced HL, and the m.3243A>G heteroplasmic mutation in the MT-TL1 gene. This method is rapid and suitable for large-scale screening because universal 96-well plates are available for use, and because an analysis of each plate can be completed within 1 h. This system detected five different mtDNA mutations in 24 of the 373 (6.4%) patients. The m.1555A>G and m.3243A>G mutations were detected in 11 (2.9%) and 9 (2.7%) patients, respectively. In addition, three mutations, that is, m.8348A>G in the MT-TK gene, m.11778G>A in the MT-ND4 gene and 15498G>A in the MT-CYB gene were detected in one patient for each. This screening system is useful for the genetic diagnosis and epidemiological study of both syndromic and non-syndromic HL.
    Journal of Human Genetics 03/2010; 55(3):147-54. · 2.53 Impact Factor
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    ABSTRACT: The purpose of the present study is to find out the clinical characteristics which determine candidates for tinnitus retraining therapy (TRT) with a sound generator (SG) as well as the prognosis of this treatment. This study enrolled 270 serious tinnitus patients who visited this institute between January 2004 and December 2008 in the TRT program. The relationships among compliance, efficacy, clinical characteristics, and affinity for SG were evaluated retrospectively. The persistence rate at one month was 61.5%. The shorter duration and higher pitch of tinnitus were significant independent predictors of compliance. Six months after the initiation of TRT, 65.2% subjects demonstrated significant relief from tinnitus. The Kaplan-Meier method demonstrated that the overall efficacy rate at 18 months was 86.5%. The lower loudness of tinnitus, recognition of tinnitus attenuation by a sound generator, and patient's positive attitude toward TRT were significant variables for predicting favorable results. The patients with lower loudness of tinnitus were suitable for TRT with a SG.
    Journal of medical and dental sciences 03/2010; 57(1):45-53.

Publication Stats

1k Citations
176.75 Total Impact Points


  • 1999–2014
    • Tokyo Medical and Dental University
      • • Tokyo Medical and Dental University Hospital
      • • Department of Otolaryngology
      • • Department of Otorhinolaryngology
      • • Department of Head and Neck Surgery
      Edo, Tōkyō, Japan
  • 2013
    • Tokyo Metropolitan Institute of Gerontology
      Edo, Tōkyō, Japan
  • 2007–2012
    • Tokyo Metropolitan Geriatric Medical Center
      Edo, Tōkyō, Japan
  • 2004
    • Asahi General Hospital
      Asahi, Chiba, Japan
    • Teikyo University
      • Department of Medicine
      Edo, Tōkyō, Japan
  • 2003
    • Gunma University
      Maebashi, Gunma Prefecture, Japan
    • Tokyo Dental College
      Edo, Tōkyō, Japan
  • 2000
    • Hamamatsu University School of Medicine
      • Department of Otorhinolaryngology
      Hamamatu, Shizuoka, Japan
    • Iwate Medical University
      • Department of Otorhinolaryngology
      Morioka, Iwate, Japan
    • Harvard Medical School
      • Department of Radiology
      Boston, MA, United States
  • 1992–2000
    • Jichi Medical University
      • Department of Otolaryngology
      Totigi, Tochigi, Japan
  • 1991
    • The University of Tokyo
      • Department of Surgical Sciences
      Tokyo, Tokyo-to, Japan