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1.
J Int Adv Otol ; 15(1): 51-55, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31058595

ABSTRACT

OBJECTIVES: We hypothesized that patients with idiopathic sudden sensorineural hearing loss (ISSHL) would have experienced more stress prior to the onset than they typically did. This study investigated stress levels in patients before the onset of ISSHL. MATERIALS AND METHODS: Forty-two patients with ISSHL were investigated. We used an original questionnaire to evaluate subjective stress levels in 1 week before onset. Serum hemoglobin A1c (HbA1c) and total cholesterol were examined to evaluate biochemical stress markers reflecting the preceding 1 to 2 months. The results on admission were compared with those at the follow-up visit. RESULTS: Significantly more patients reported greater physical exhaustion, greater mental exhaustion, or a worse physical condition on admission than at follow-up (p<0.01, for each variable). On admission, 81% of patients reported greater than normal stress with regard to at least 1 of 3 items. The mean serum HbA1c was slightly but nonsignificantly lower at the follow-up visit (p=0.10), while the mean serum total cholesterol was significantly lower at follow-up than on admission (p<0.01). CONCLUSION: The results indicate that patients were under a greater degree of stress before the onset of ISSHL, suggesting that stress plays a role in inducing ISSHL.


Subject(s)
Cholesterol/blood , Glycated Hemoglobin/analysis , Hearing Loss, Sensorineural/psychology , Hearing Loss, Sudden/psychology , Adult , Aged , Biomarkers/metabolism , Female , Hearing Loss, Sensorineural/blood , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sudden/blood , Hearing Loss, Sudden/diagnosis , Humans , Male , Middle Aged , Patient Admission/statistics & numerical data , Stress, Physiological , Surveys and Questionnaires
2.
Auris Nasus Larynx ; 45(5): 1053-1060, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29752155

ABSTRACT

OBJECTIVE: Curative synchronous double primary cancers of the head and neck and the esophagus (CSC-HE) are frequently detected, but a standard treatment remains to be established. We studied the clinical course to explore appropriate treatment strategies. METHODS: We retrospectively studied consecutive 33 patients who had CSC-HE. The disease stage was classified into 4 groups: group A, early head and neck cancer (HNC) and early esophageal cancer (EC); group B, early HNC and advanced EC; group C, advanced HNC and early EC; and group D, advanced HNC and advanced EC. As induction chemotherapy, the patients received 3 courses of TPF therapy (docetaxel 75mg/m2 on day 1, cisplatin 75mg/m2 on day 1, and 5-fluorouracil 750mg/m2 on days 1-5) at 3-week intervals. The clinical courses and treatment outcomes were studied according to the disease stage of CSC-HE. RESULTS: The disease stage of CSC-HE was group A in 1 patient (3%), group B in 9 patients (27.3%), group C in 3 patients (9.1%), and group D in 20 patients (60.6%). The median follow-up was 26months, and the 2-year overall survival rate was 67.4%. In groups A, B, and C, the 2-year overall survival rate was 83.3%. In group D, the 2-year overall survival rate was 62.6%. Ten of 20 patients in group D received induction chemotherapy with TPF, and 6 patients were alive and disease free at the time of this writing. CONCLUSION: The treatment outcomes of patients with CSC-HE were relatively good. TPF induction chemotherapy might be an effective treatment for patients with advanced HNC and advanced EC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Esophageal Squamous Cell Carcinoma/therapy , Neoplasms, Multiple Primary/therapy , Squamous Cell Carcinoma of Head and Neck/therapy , Adult , Aged , Aged, 80 and over , Cisplatin/therapeutic use , Esophageal Squamous Cell Carcinoma/pathology , Female , Fluorouracil/therapeutic use , Humans , Induction Chemotherapy , Male , Middle Aged , Neoplasm Staging , Neoplasms, Multiple Primary/pathology , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/pathology , Survival Rate , Taxoids/therapeutic use , Treatment Outcome
3.
Auris Nasus Larynx ; 44(1): 33-39, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27160786

ABSTRACT

OBJECTIVE: To document the clinical features and associated pure-tone audiometry data in patients with enlargement of the vestibular aqueduct (EVA), and to identify risk factors for fluctuating hearing loss (HL) and vertigo/dizziness in EVA patients. METHODS: In this nationwide survey in Japan, a first survey sheet was mailed to 662 board-certified otolaryngology departments to identify the ones treating EVA patients. A second survey sheet, which contained solicited clinical information and the results of the hearing tests, was mailed to all facilities that reported treating EVA cases. We analyzed clinical information, including age at the time of the most recent evaluation, gender, EVA side, age at onset, initial symptoms, precipitating factors, and etiology from survey responses, and assessed 4-frequency (500, 1000, 2000, and 4000Hz) pure-tone average (PTA) from accompanying pure-tone audiometry data. A multivariate logistic regression analysis was utilized to identify the possible risk factors for fluctuating HL and vertigo/dizziness. RESULTS: In total, 513 hospitals (response rate, 77.5%) responded to the first survey, and 113 reported treating patients with EVA. Seventy-nine out of the 113 hospitals (response rate 69.9%) responded to the second survey, and the data of 380 EVA patients were registered and analyzed. Of the 380 patients, 221 (58.2%) were female, suggesting female preponderance. The patient age ranged from 0 to 73 years (mean, 16.7 years; median, 13 years; interquartile range, 6-24 years). EVA was bilateral in 91.1% of the patients (346/380). The most prevalent initial symptom was HL (341/380), followed by vertigo/dizziness/imbalance (34/380). Sudden HL occurred secondary to head trauma in 5.3% of the patients and upper respiratory infection in 5.0%. Pure-tone audiometry showed profound HL (PTA >91dB) in 316 (52.0%) of the 608 ears in the 304 patients tested, and asymmetric HL, defined as >10dB, in 147 (48.4%) of the 304 patients. The mean PTA was 83.7dB (median, 91.3dB; interquartile range, 71.3-103.8dB), and the severity in PTA did not correlate with age. Multivariate logistic regression identified age ≥10 years (compared to age of 0-9 years), bilateral HL (compared to unilateral HL/normal hearing), a history of head trauma, and Pendred syndrome (compared to the other EVA-associated disorders) as significant risk factors for fluctuating HL and/or vertigo/dizziness. CONCLUSION: The present nationwide survey of 380 EVA patients provided a more precise description of the clinical features, including risk factors for fluctuating HL and vertigo/dizziness.


Subject(s)
Dizziness/epidemiology , Hearing Loss, Sensorineural/epidemiology , Hearing Loss, Sudden/epidemiology , Vertigo/epidemiology , Vestibular Aqueduct/abnormalities , Adolescent , Adult , Aged , Audiometry, Pure-Tone , Child , Child, Preschool , Craniocerebral Trauma/epidemiology , Female , Goiter, Nodular/epidemiology , Hearing Loss, Bilateral/epidemiology , Hearing Loss, Bilateral/physiopathology , Hearing Loss, Sensorineural/physiopathology , Hearing Loss, Sudden/physiopathology , Hearing Loss, Unilateral/epidemiology , Hearing Loss, Unilateral/physiopathology , Humans , Infant , Infant, Newborn , Japan/epidemiology , Logistic Models , Male , Middle Aged , Multivariate Analysis , Risk Factors , Vestibular Aqueduct/physiopathology , Young Adult
4.
Jpn J Clin Oncol ; 47(1): 47-53, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27677662

ABSTRACT

BACKGROUND: Little is known about quality of life and functional status of patients with terminally ill head and neck cancers. METHODS: We conducted a multicenter, prospective, observational study to examine quality of life and functional status in terminally ill head and neck cancer patients. RESULTS: Of the 100 patients meeting inclusion criteria, 72 were observed until death. There was no significant difference in the quality of life score between baseline and Week 3. Forty patients (54.9%) could speak and 22 patients (30.5%) could have oral intake upon study entry. Fifty-three patients (74.6%) received enteral nutrition. Twenty-six patients (36.6%) required dressing changes for fungating tumors. The route of nutritional intake (nasogastric tube vs. percutaneous gastric tube) might be predictive for the duration of hospital stay (64 vs. 21 days, P = 0.0372). CONCLUSION: There was no significant relationship between quality of life and functional status seen in this study. Feeding tube type could have the most impact on quality of life.


Subject(s)
Head and Neck Neoplasms/pathology , Quality of Life , Adult , Aged , Enteral Nutrition , Female , Head and Neck Neoplasms/mortality , Health Status , Humans , Intubation, Gastrointestinal , Japan , Length of Stay , Male , Middle Aged , Prospective Studies , Survival Rate , Terminally Ill , Tertiary Care Centers
5.
Acta Otolaryngol ; 136(5): 465-9, 2016.
Article in English | MEDLINE | ID: mdl-26882452

ABSTRACT

CONCLUSION: The results suggest that SOD1 rs4998557 could be associated with susceptibility to SSNHL in the Japanese population. OBJECTIVES: To assess the gene association with sudden sensorineural hearing loss (SSNHL). METHODS: A two-stage case control study was conducted to explore the relationship of the candidate genes to SSNHL. The 192 gene samples from SSNHL patients registered in the intractable inner ear disease gene bank were enrolled. As the candidate genes, 39 SNPs from 31 genes were selected for the first stage study. The second stage study examined whether the SOD1 gene polymorphisms, defined by significant differences between cases and controls in the first stage study, are associated with SSNHL. RESULTS: Significant differences were observed in four SNPs from three genes, Glutathione-S-transferase pai 1 (GSTP1), proteine kinase C heta (PRKCH), and superoxide dismutase 1 (SOD1), in terms of allele frequency between SSNHL patients and HapMap controls. In the SOD1 gene, a significant difference was observed in the dominant model study of the SNP rs4998557 in the second stage study. Furthermore, as a result of dividing SSNHL patients based on the clinical data, the difference was more apparent in the case of the over 60 dB group and the tinnitus-positive group.


Subject(s)
Hearing Loss, Sensorineural/genetics , Hearing Loss, Sudden/genetics , Superoxide Dismutase-1/genetics , Adult , Aged , Case-Control Studies , Female , Genotype , Glutathione S-Transferase pi/genetics , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide
6.
Ann Otol Rhinol Laryngol ; 125(6): 508-15, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26755795

ABSTRACT

OBJECTIVES: Paralyzed tissue due to long-term denervation is resistant to many treatments because it induces irreversible histological changes and disorders of deglutition or phonation. We sought to determine the effect of autologous transplantation of fascia into the vocal fold (ATFV) with controlled release of basic fibroblast growth factor (bFGF) on long-term unilateral vocal fold paralysis (UVFP). METHODS: Unilateral recurrent laryngeal nerve (RLN) section was performed on 20 rats. Five rats were implanted with autologous fascia only (fascia group), and 10 rats were implanted with autologous fascia and a gelatin hydrogel sheet with 1 µg (1 µg bFGF + fascia group) or 0.1 µg (0.1 µg bFGF + fascia group) of bFGF 4 months after RLN section. We evaluated the normalized glottal gap and laryngeal volume and histological changes 3 months after implantation. RESULTS: The normalized glottal gap was significantly reduced in the 3 fascia implantation groups. Normalized laryngeal volume, fat volume, and lateral thyroarytenoid muscle volume were significantly increased in the 2 fascia implantation with bFGF groups. CONCLUSIONS: The ATFV with controlled release of bFGF repaired the glottal gap and laryngeal volume after RLN section and may reduce the occurrence of aspiration and hoarseness. We speculate that this treatment improves laryngeal function in long-term RLN denervation.


Subject(s)
Fascia/transplantation , Fibroblast Growth Factors/administration & dosage , Recurrent Laryngeal Nerve/surgery , Vocal Cord Paralysis/therapy , Vocal Cords/surgery , Animals , Delayed-Action Preparations , Fibroblast Growth Factors/pharmacology , Hydrogels , Laryngeal Muscles/drug effects , Laryngeal Muscles/innervation , Laryngeal Muscles/pathology , Larynx/drug effects , Larynx/pathology , Male , Organ Size , Rats , Rats, Sprague-Dawley , Transplantation, Autologous , Vocal Cords/drug effects , Vocal Cords/innervation
8.
Auris Nasus Larynx ; 43(3): 304-8, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26527517

ABSTRACT

OBJECTIVE: Urinary leukotriene E4 (U-LTE4) concentrations are significantly elevated in patients with aspirin-intolerant asthma (AIA). However, the relationship between the clinicopathogenetic features of eosinophilic rhinosinusitis and U-LTE4 concentration remains unknown. Here we examined the relationship between U-LTE4 level and eosinophil in chronic rhinosinusitis. METHODS: We measured the U-LTE4 concentrations and eosinophil counts in ethmoidal and maxillary sinuses and peripheral blood in 30 asthmatic patients (including 15 AIA patients). RESULTS: Eosinophil counts in ethmoidal sinuses and peripheral blood were markedly higher in asthmatic patients than in controls. Although there were no significant differences between eosinophil counts in maxillary and ethmoidal sinuses for ATA group, eosinophil counts were higher in ethmoidal sinus compared to that in maxillary sinus in the AIA group (P<.05). Eosinophil counts were higher in the maxillary than in ethmoidal sinuses for control patients (P<.05). Despite low correlation between eosinophil counts in peripheral blood and eosinophil counts in maxillary sinus (rs=0.4323, P<.001), moderate correlation was observed between eosinophil counts in peripheral blood and eosinophil counts in ethmoidal sinus (rs=0.5249, P<.0001). Basal U-LTE4 concentrations were higher in AIA patients than in those with aspirin-tolerant asthma. Despite low correlation between eosinophil counts and U-LTE4 concentration in maxillary sinus (rs=0.3849, P<.01), moderate correlation was observed between eosinophil counts and U-LTE4 concentrations in ethmoidal sinus (rs=0.4736, P<.001). CONCLUSION: We describe the differences in U-LTE4 and other parameters in AIA compared to ATA, and correlation among parameters. We demonstrate that eosinophil-dominant inflammation starts in ethmoidal sinus clinicopathogenetically in CRS with asthma. U-LTE4 concentration was not exclusively associated with eosinophil counts in ethmoidal sinus. Eosinophils in ethmoidal sinus may be a major production site for CysLTs, particularly in AIA. CRS with AIA is assumed to be characterized by leukotriene-eosinophil cross-interaction in ethmoidal sinus.


Subject(s)
Asthma, Aspirin-Induced/immunology , Eosinophilia/immunology , Eosinophils/cytology , Ethmoid Sinus/cytology , Leukotriene E4/urine , Maxillary Sinus/cytology , Rhinitis/immunology , Sinusitis/immunology , Adult , Aged , Asthma/complications , Asthma/immunology , Asthma/urine , Asthma, Aspirin-Induced/complications , Asthma, Aspirin-Induced/urine , Case-Control Studies , Chronic Disease , Eosinophilia/complications , Female , Humans , Leukocyte Count , Male , Middle Aged , Rhinitis/complications , Rhinitis/urine , Sinusitis/complications , Sinusitis/urine , Young Adult
9.
Auris Nasus Larynx ; 43(3): 217-28, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26654157

ABSTRACT

OBJECTIVE: The methods to evaluate the efficacy of the adjusted hearing aid for a hearing-impaired person are fitting tests. The tests include those presently carried out for evaluating hearing aid fitting, and the methods of testing and evaluation have been published as "Guidelines for the evaluation of hearing aid fitting (2010)" by the Japan Audiological Society. METHODS: Guidelines for the following 8 test methods are presented. (1) Measurements of speech performance-intensity functions and speech recognition scores; (2) Assessment of hearing aid fitting from the aspect of tolerance of environmental noise; (3) Measurement of real-ear insertion gain (measurement of sound pressure levels at the eardrum); (4) Measurement of the hearing threshold level and the uncomfortable loudness level (UCL) in sound pressure level (SPL) with an inserted earphone; (5) Aided threshold test in a sound field (functional gain measurement); (6) Prediction of insertion gain and aided threshold from hearing aid characteristics and the pure tone audiogram; (7) Measurement of speech recognition in noise; (8) Assessment of hearing aid fitting using questionnaires. In the above tests, (1) and (2) are mandatory tests, and (3) to (8) are informative tests. RESULTS: By performing test combinations properly selected from the above 8 tests, the benefits of a hearing aid could be determined. CONCLUSION: The above test methods were useful and valuable in determining the efficacy of the adjusted hearing aid for a hearing-impaired person during clinical practice.


Subject(s)
Hearing Aids , Hearing Loss/rehabilitation , Prosthesis Fitting/standards , Audiology , Auditory Threshold , Humans , Japan , Noise , Societies, Scientific , Speech Reception Threshold Test
10.
Nihon Jibiinkoka Gakkai Kaiho ; 118(5): 657-61, 2015 May.
Article in Japanese | MEDLINE | ID: mdl-26349278

ABSTRACT

Deep neck abscesses are relatively rare in children compared with adults. Diagnosis can be difficult in pediatric patients because of the various clinical symptoms, therefore, it is important to correctly understand the pathology. We report herein on a rare pediatric case of a deep neck abscess that caused multiple instances of cranial nerve palsy. The patient was a 7-year-old boy who, despite treatment by a local physician for fever, swelling of the left neck and neck pain, developed torticollis, dysarthria, dysphagia and hoarseness and consequently consulted our department. We observed palsy associated with the IX, X, and XII left cranial nerves and a retropharyngeal abscess was diagnosed based on the computed tomography findings. The patient was hospitalized and underwent conservative treatment, and on day 21 of hospitalization, the patient was discharged after his symptoms had eased and the size of the abscess had reduced. We believe that palsy of the cranial nerves in the present case occurred as a result of pressure being applied to the cranial nerves in the carotid space due to an abscess in the retropharyngeal space.


Subject(s)
Cranial Nerve Diseases/etiology , Retropharyngeal Abscess/complications , Child , Drug Combinations , Humans , Male , Retropharyngeal Abscess/diagnostic imaging , Retropharyngeal Abscess/drug therapy , Tomography, X-Ray Computed
11.
Jpn J Clin Oncol ; 45(8): 732-7, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25981622

ABSTRACT

OBJECTIVE: Supracricoid laryngectomy with cricohyoidoepiglottopexy has been known to be able to cope with tumor excisions with minimal margins. Extended resection may result in a limited margin and may impair the prognosis. We conducted a clinicopathologic analysis of local recurrence in supracricoid laryngectomy with cricohyoidoepiglottopexy patients. METHODS: Between 1997 and 2013, 100 patients with glottic cancers underwent supracricoid laryngectomy with cricohyoidoepiglottopexy. The clinicopathologic findings were evaluated. We also analyzed: (i) cancer-specific and overall survival rates, (ii) the correlation between locoregional recurrence and overall survival, (iii) T staging and larynx preservation rates and (iv) previous radiation history and larynx preservation rates. RESULTS: Local recurrence was recognized in eight of the 100 patients (8%); all were initially staged as T3 or T4. Recurrence was identified in the submucosal regions of the ipsilateral arytenoid and/or infraglottis. Six patients were salvaged by completion total laryngectomy except two. Cancer-specific survival at 5 years was 93%; overall survival at 5 years was 89%. There was no significant difference between overall survival and locoregional recurrence. There was a significant difference between larynx preservation in T1-2 and T3-4 patients. There was no significant difference between larynx preservation and the previous radiation therapy status. CONCLUSIONS: Our experience convinced us of the clinical potential of supracricoid laryngectomy with cricohyoidoepiglottopexy as one of the effective options for functional larynx preservation. Supracricoid laryngectomy with cricohyoidoepiglottopexy is the most suitable for unfavorable T2 and T3a cases and is applicable for appropriately selected radiation-failed patients. Thorough pre-operative evaluation, proper surgical techniques and careful follow-up are prerequisites for the success of supracricoid laryngectomy with cricohyoidoepiglottopexy.


Subject(s)
Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Neoplasm Recurrence, Local , Organ Sparing Treatments/methods , Adult , Aged , Cricoid Cartilage , Female , France , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Retrospective Studies , Salvage Therapy/methods , Survival Analysis , Treatment Outcome
12.
Auris Nasus Larynx ; 42(2): 163-6, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25450856

ABSTRACT

OBJECTIVE: The case of a thirteen-year-old woman showing an atypical teratoid/rhabdoid tumor (AT/RT) primarily occurred in the internal auditory canal was presented. RESULTS: There was a delay in diagnosing AT/RT because of the first histological diagnosis of benign neurofibroma. If we had changed the surgical approach to one which was middle cranial fossa-based or translabyrinthine in the second or third operation, we might have reached an earlier final diagnosis. Although we faced a dilemma about whether to sacrifice facial nerve function for dissection of the tumor, we should have considered the possibility of malignancy at an earlier stage. CONCLUSION: This is a case report of AT/RT in the internal auditory canal presenting with progressive hearing loss as the initial symptom. Although no previous reports of AT/RT primarily occurring in the internal auditory canal are existent, this rare form of the disease should be considered in future evaluations as a differential diagnosis for internal auditory canal tumor.


Subject(s)
Ear Neoplasms/diagnosis , Ear, Inner/pathology , Facial Paralysis/diagnosis , Hearing Loss, Sensorineural/diagnosis , Rhabdoid Tumor/diagnosis , Teratoma/diagnosis , Adolescent , Ear Neoplasms/complications , Ear Neoplasms/surgery , Ear, Inner/surgery , Facial Paralysis/etiology , Female , Hearing Loss, Sensorineural/etiology , Humans , Magnetic Resonance Imaging , Rhabdoid Tumor/complications , Rhabdoid Tumor/surgery , Teratoma/complications , Teratoma/surgery
13.
Auris Nasus Larynx ; 41(3): 249-54, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24411828

ABSTRACT

OBJECTIVE: This study was conducted to evaluate the relationship between hearing and cochlear histopathology after arginine vasopressin administration in rats. METHODS: A total of 30 Wistar rats were injected with either 0.02 unit/g of arginine vasopressin or the same amount of isotonic saline solution. The initial auditory brain stem response threshold was recorded and additional measurements were made at 10, 30, 60, and 90 min after injection of arginine vasopressin or isotonic saline solution. The threshold for each timepoint was compared with the initial threshold. Histological quantitative assessment of endolymphatic hydrops in the cochlea was performed using light microscopy and assessment of the basal, intermediate, and marginal cells of the stria vascularis was performed with electron microscopy. RESULTS: The auditory brain stem threshold 60 min after arginine vasopressin injection increased significantly in comparison with the initial threshold (P<0.05). Although the index for endolymphatic hydrops in rats administered arginine vasopressin was not different from that in controls (P>0.05), vacuoles in the intermediate cells were increased significantly in the treated rats (P<0.01). CONCLUSION: Hearing impairment was detected without endolymphatic hydrops in rats administered arginine vasopressin. An increase of vacuoles in the intermediate cells may account for the hearing impairment induced by arginine vasopressin injection.


Subject(s)
Arginine Vasopressin/pharmacology , Cochlea/drug effects , Endolymphatic Hydrops/chemically induced , Evoked Potentials, Auditory, Brain Stem/drug effects , Vasoconstrictor Agents/pharmacology , Animals , Auditory Threshold/drug effects , Cochlea/pathology , Cochlea/ultrastructure , Endolymphatic Hydrops/pathology , Evoked Potentials, Auditory, Brain Stem/physiology , Microscopy, Electron , Rats , Rats, Wistar , Stria Vascularis/drug effects , Stria Vascularis/ultrastructure
14.
Cancer Sci ; 105(2): 202-10, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24219164

ABSTRACT

Effective molecular target drugs that improve therapeutic efficacy with fewer adverse effects for esophageal cancer are highly anticipated. Poly(ADP-ribose) polymerase (PARP) inhibitors have been proposed as low-toxicity agents to treat double strand break (DSB)-repair defective tumors. Several findings imply the potential relevance of DSB repair defects in the tumorigenesis of esophageal squamous cell carcinoma (ESCC). We evaluated the effect of a PARP Inhibitor (AZD2281) on the TE-series ESCC cell lines. Of these eight cell lines, the clonogenic survival of one (TE-6) was reduced by AZD2281 to the level of DSB repair-defective Capan-1 and HCC1937 cells. AZD2281-induced DNA damage was implied by increases in γ-H2AX and cell cycle arrest at G2/M phase. The impairment of DSB repair in TE-6 cells was suggested by a sustained increase in γ-H2AX levels and the tail moment calculated from a neutral comet assay after X-ray irradiation. Because the formation of nuclear DSB repair protein foci was impaired in TE-6 cells, whole-exome sequencing of these cells was performed to explore the gene mutations that might be responsible. A novel mutation in RNF8, an E3 ligase targeting γ-H2AX was identified. Consistent with this, polyubiquitination of γ-H2AX after irradiation was impaired in TE-6 cells. Thus, AZD2281 induced growth retardation of the DSB repair-impaired TE-6 cells. Interestingly, a strong correlation between basal expression levels of γ-H2AX and sensitivity to AZD2281was observed in the TE-series cells (R(2)  = 0.5345). Because the assessment of basal DSB status could serve as a biomarker for selecting PARP inhibitor-tractable tumors, further investigation is warranted.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Esophageal Neoplasms/drug therapy , Phthalazines/pharmacology , Piperazines/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Cell Cycle Checkpoints/drug effects , Cell Division/drug effects , Cell Line, Tumor , DNA Damage/drug effects , DNA Repair/drug effects , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Esophageal Neoplasms/enzymology , Esophageal Neoplasms/genetics , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma , G2 Phase/drug effects , Histones/genetics , Histones/metabolism , Humans , MCF-7 Cells , Molecular Sequence Data , Mutation/drug effects , Mutation/genetics , Phthalazines/adverse effects , Piperazines/adverse effects , Ubiquitin-Protein Ligases
15.
Jpn J Clin Oncol ; 44(1): 57-64, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24174633

ABSTRACT

OBJECTIVE: We analyzed the clinical outcomes of 849 laryngeal cancers treated in the past 40 years, which overlapped with the era of the global treatment shift. METHODS: To compare the chronological outcomes, patients were divided into four groups according to their registration year as 1972-82, 1983-92, 1993-2002 and 2003-12; treatment trends, larynx preservation rate and overall survival rate were compared. RESULTS: There were 104, 173, 253 and 319 patients registered in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. Five-year overall survival rates were 74, 76.5, 75.6 and 82.2% in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. The five-year larynx preservation rates were 65.5, 75.7, 75.4 and 80.9% in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. CONCLUSIONS: The number of patients treated at our institute increased, and the overall survival and larynx preservation rates exhibited favorable improvements over the past four decades. In the analysis of nonsurgical options, S1 combined radiotherapy showed superiority over concurrent chemoradiotherapy and radiotherapy in larynx preservation, and S1 combined radiotherapy, concurrent chemoradiotherapy and Tegafur Uracil combined radiotherapy showed superiority over radiotherapy in overall survival. In nonsurgical approaches, proper case selection is the key to success and may be much more important than pursuing radiotherapy dose escalation. In the analysis of surgical options, laser and supracricoid laryngectomy with cricohyoidoepiglottopexy contributed to larynx preservation in early- and intermediate-stage cancers, respectively. Supracricoid laryngectomy with cricohyoidoepiglottopexy demonstrated overall survival not worse than total laryngectomy, which is the prerequisite treatment basis for larynx preservation options. We must make extra efforts in pursuing an ideal balance between nonsurgical and surgical larynx preservation options.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Laryngeal Neoplasms/epidemiology , Laryngeal Neoplasms/therapy , Laryngectomy/statistics & numerical data , Organ Sparing Treatments/statistics & numerical data , Aged , Chemotherapy, Adjuvant , Female , Humans , Kaplan-Meier Estimate , Laryngeal Neoplasms/drug therapy , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Radiotherapy, Adjuvant , Retrospective Studies , Treatment Outcome
16.
Otol Neurotol ; 34(8): 1405-10, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24026023

ABSTRACT

OBJECTIVE: This study evaluated self-reported symptoms in patients with idiopathic sudden sensorineural hearing loss (ISSHL). STUDY DESIGN: Cross-sectional study. SETTING: Multicenter clinical investigation in 9 university hospitals. PATIENTS: In total, 140 patients with ISSHL and 24 patients with unilateral sensorineural hearing loss (USHL; control) were included. MAIN OUTCOME MEASURES: A questionnaire on symptoms of ISSHL was distributed and the Short-Form Health Survey (Version 2) was used for assessing the quality of life. RESULTS: In response to questions on hearing difficulty, many of patients in both groups experienced symptoms. In response to questions on hearing-related discomfort, a significantly higher number of patients with ISSHL experienced symptoms compared with those with USHL. Compared with a high incidence of tinnitus in patients with ISSHL, very low incidence of tinnitus was observed in those with USHL.In the multiple linear regression analysis, hearing-related discomfort was the sole significant factor on the Mental Component Summary scores of the Short-Form Health Survey (Version 2). CONCLUSION: Many patients with ISSHL experience several symptoms such as hearing difficulty, hearing-related discomfort, tinnitus, and anxiety. Hearing-related discomfort strongly affected the quality of life in patients with ISSHL.


Subject(s)
Diagnostic Self Evaluation , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sudden/diagnosis , Adult , Aged , Aged, 80 and over , Anxiety/complications , Anxiety/diagnosis , Cross-Sectional Studies , Female , Health Surveys , Hearing Loss, Sensorineural/complications , Hearing Loss, Sudden/complications , Humans , Male , Middle Aged , Quality of Life , Self Report , Surveys and Questionnaires , Tinnitus/complications , Tinnitus/diagnosis
17.
Jpn J Clin Oncol ; 43(8): 782-7, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23749982

ABSTRACT

BACKGROUND: For years, it has been a major interest for surgeons and oncologists to develop a novel technique to detect hypopharyngeal cancers at an early stage and to treat the lesions in a less invasive manner. The advent of the narrow band imaging system combined endoscopy and various endoscopic approaches shed light on the new era of the minimum invasive management of superficial cancers in hypopharyngeal regions. METHODS: Three endoscopic approaches, endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic laryngopharyngeal surgery, were chronologically introduced at our institute. In this study, we focused on the clinical outcomes, advantages and limitations of each procedure. RESULTS: A total of 30 patients (42 procedures) received transoral pharyngectomies between June 2006 and May 2012. Tracheotomy was performed in 9 of 42 (21%) patients. Three patients developed local recurrence and were subsequently controlled by additional transoral pharyngectomies. The 2- and 5-year local control rates were 92.8 and 83.5%. The 2- and 5-year overall survival rates were 82.1%. CONCLUSIONS: Endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic laryngopharyngeal surgery-transoral pharyngectomies are useful procedures for treating superficial hypopharyngeal cancers. Endoscopic mucosal resection manifested the least invasiveness and may be beneficial for resecting small superficial lesions, endoscopic submucosal dissection may be advantageous for patients with difficult laryngopharyngeal exposure and endoscopic laryngopharyngeal surgery has shown the optimal effectiveness and minimal complications and can be applied to most of the hypopharyngeal sub-sites. All three procedures require a high level of technical skill and close collaboration between otolaryngologists and gastroenterologists.


Subject(s)
Hypopharyngeal Neoplasms/pathology , Hypopharyngeal Neoplasms/surgery , Pharyngectomy/methods , Adult , Aged , Dissection , Endoscopy , Female , Follow-Up Studies , Gastroenterology , Humans , Interdisciplinary Communication , Male , Middle Aged , Mouth , Neoplasm Recurrence, Local/surgery , Otolaryngology , Pharyngectomy/adverse effects , Pharyngectomy/instrumentation , Tracheotomy
18.
Otol Neurotol ; 34(4): 644-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23657210

ABSTRACT

OBJECTIVE: To assess the perception of hearing handicap in adult patients with unilateral sudden sensorineural hearing loss (SNHL) compared with those with bilateral SNHL or unilateral congenital SNHL. STUDY DESIGN: Retrospective chart review. SETTING: Multicenter department of otolaryngology referrals. PATIENTS: Seventy-one subjects in the unilateral severe-profound (>70 dB) sudden SNHL group (Group 1), 17 subjects in the unilateral prelingual or congenital SNHL group (Group 2), and 121 subjects in the bilateral SNHL group (Group 3). INTERVENTIONS: Questionnaire. MAIN OUTCOME MEASURES: Hearing Handicap Inventory for Adults (HHIA) and visual analogue scale (VAS) measurements of hearing handicap. RESULTS: Average levels of hearing loss were 92 dB in Group 1, 109 dB in Group 2, and 67 dB in Group 3. The relative percentage scores of HHIA and VAS compared with Group 3 were 72.6% and 81.0% in Group 1 and 25.4% and 50.3% in Group 2, respectively. A mild correlation between the HHIA subscale or VAS scores and degree of hearing loss could be found in Group 3. No significant correlation was found between the HHIA subscale or VAS scores and duration of hearing loss in Group 1 or Group 3. Higher scores were obtained in male subjects than in female subjects. Patients in Group 1 who were troubled by tinnitus scored significantly higher in the HHIA. In multiple logistic regression analysis, presence of tinnitus, older age, higher average hearing loss level, and group (bilateral SNHL>unilateral sudden SNHL>unilateral precongenital SNHL) revealed a significant positive association with high score (>42) of HHIA (odds ratio, 3.171, 1.021, 1.031, and 6.690, respectively). CONCLUSION: The results of HHIA and VAS suggest that not only patients with bilateral SNHL but also those with unilateral sudden SNHL, particularly those who have tinnitus, experience a hearing handicap.


Subject(s)
Hearing Loss, Bilateral/physiopathology , Hearing Loss, Sensorineural/physiopathology , Hearing Loss, Unilateral/physiopathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Surveys and Questionnaires , Visual Analog Scale
19.
Am J Clin Pathol ; 139(5): 587-98, 2013 May.
Article in English | MEDLINE | ID: mdl-23596110

ABSTRACT

An immunohistochemical study was conducted of 108 papillary carcinoma cases, including 48 cases with intratumoral heterotopic ossification (IHO). In 48 cases, papillary carcinoma with IHO was accompanied by nodular fibrosis. Cases of papillary carcinoma with IHO or nodular fibrosis showed higher incidences of lymph node metastasis, multifocal lesions, and extrathyroidal invasion than those without IHO and nodular fibrosis. A higher number of stromal myofibroblasts was observed in papillary carcinoma with IHO or nodular fibrosis than in that without fibrosis. Expression of both basic fibroblast growth factor (bFGF) and bone morphogenetic protein (BMP)-2 was the highest in papillary carcinoma with IHO. Papillary carcinoma with IHO showed higher vascular invasion and higher numbers of capillaries expressing nestin, which is associated with high expression of vascular endothelial growth factor (VEGF). Papillary carcinoma with IHO is a unique subtype with extensive progression including frequent lymph node metastasis, multifocality, and invasive behavior. Papillary carcinoma with IHO was correlated with expression of bFGF, BMP-2, and VEGF in the carcinoma cells, leading to neovascularization.


Subject(s)
Adenocarcinoma, Papillary/secondary , Ossification, Heterotopic/pathology , Thyroid Neoplasms/pathology , Adenocarcinoma, Follicular/blood supply , Adenocarcinoma, Follicular/metabolism , Adenocarcinoma, Follicular/secondary , Adenocarcinoma, Papillary/blood supply , Adenocarcinoma, Papillary/metabolism , Biomarkers, Tumor/metabolism , Bone Morphogenetic Protein 2 , Capillaries/metabolism , Capillaries/pathology , Disease Progression , Fibroblast Growth Factor 2/metabolism , Fibrosis/pathology , Humans , Intermediate Filament Proteins/metabolism , Lymph Nodes/pathology , Lymphatic Metastasis , Microcirculation , Middle Aged , Neoplasms, Multiple Primary , Neovascularization, Pathologic , Nerve Tissue Proteins/metabolism , Nestin , Ossification, Heterotopic/metabolism , Thyroid Neoplasms/blood supply , Thyroid Neoplasms/metabolism , Vascular Endothelial Growth Factor A/metabolism
20.
Dig Endosc ; 25 Suppl 1: 39-43, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23480401

ABSTRACT

The objectives of surveillance after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma are: (i) early detection and treatment of recurrence; and (ii) early detection and treatment of metachronous esophageal squamous cell carcinoma and second primary cancers. Protocols for follow up after EMR or ESD for esophageal squamous cell carcinoma should be based on the risks of lymph node metastasis and distant metastasis as assessed on the basis of tumor staging at initial treatment. Early detection of recurrence or metachronous carcinomas often allows curative or less invasive treatment. Particular attention should be paid to the development of metachronous esophageal squamous cell carcinomas and second primary cancers (in particular, head and neck cancer and gastric cancer because of their high incidence).


Subject(s)
Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Esophagoscopy , Neoplasm Recurrence, Local/diagnosis , Neoplasms, Multiple Primary/diagnosis , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Cohort Studies , Disease Progression , Dissection , Endoscopy, Digestive System , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Follow-Up Studies , Humans , Japan , Lymphatic Metastasis/pathology , Mucous Membrane/pathology , Mucous Membrane/surgery , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/surgery , Risk Factors
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