Mariko Hiramatsu

Association of interleukin‐1 gene polymorphisms with sudden sensorineural hearing loss and Ménière’s disease

Sudden sensorineural hearing loss (SSNHL) and Ménière’s disease are the most common inner ear diseases in which the causes are unknown. As recent magnetic resonance imaging has demonstrated disruption of the blood–labyrinth barrier in these inner ear diseases, inflammatory reaction associated with increased permeability of the blood vessels may be involved. The genotypes of interleukin 1A (IL1A) (−889C/T; rs1800587) and interleukin 1B (IL1B) (−511C/T; rs16944) were determined using an allele‐specific primer–polymerase chain reaction method in 72 patients with SSNHL, 68 patients with Ménière’s disease, and 2202 control subjects living almost in the same area as the patients. A significantly higher prevalence of the IL1A−889T allele was observed in SSNHL and Ménière’s disease compared with controls, although no significant difference in distribution of IL1B−511C/T genotypes was observed between the patients and controls. Adjusted odd ratios for SSNHL and Ménière’s disease risks in the −889TT genotypes were 25.89 (95% confidence interval (CI) 12.19–54.98) and 18.20 (95% CI 7.80–42.46), respectively, after age and gender were taken as moderator variables. Our results suggested that IL1A is closely associated with susceptibility of SSNHL and Ménière’s disease.

Polymorphisms in Genes Involved in Inflammatory Pathways in Patients with Sudden Sensorineural Hearing Loss

Abstract: Although the etiology of idiopathic sudden sensorineural hearing loss (SSNHL) remains unclear, the pathologically increased permeability of blood vessels, elucidated by gadolinium-enhanced magnetic resonance imaging (MRI), suggests the involvement of inflammation. Because SSNHL is considered a multifactorial disease, possibly caused by interactions between genetic factors and environmental factors, the authors investigated the associations of polymorphisms of inflammatory mediator genes with susceptibility to SSNHL. The authors compared 72 patients affected by SSNHL and 2010 adults (1010 men and 1000 women; mean age 59.2 years; range 40–79) who participated in the National Institute for Longevity Sciences Longitudinal Study of Aging. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL in subjects with polymorphisms in the genes IL-6 C − 572G, IL-4R G1902A, IL-10 A − 592C, TNFα C − 863A, TNFRSF1B G593A, VEGF C936T, VEGF C − 2578A, and VEGF G − 1154A, with adjustment for age, gender, and any history of hypertension, diabetes, or dyslipidemia. The per-allele OR for the risk of SSNHL in subjects bearing IL-6 C − 572G was 1.480 (95% confidence interval [CI], 1.037–2.111) in model 1 (no adjustment), 1.463 (CI, 1.022–2.094) in model 2 (adjusted for age and gender), and 1.460 (CI, 1.016–2.097) in model 3 (adjusted for age, gender, and a history of hypertension, diabetes, or dyslipidemia). Under the dominant model of inheritance, the ORs were 1.734 (CI, 1.080–2.783) in model 1, 1.690 (CI, 1.050–2.721) in model 2, and 1.669 (CI, 1.035–2.692) in model 3. The remaining seven polymorphisms failed to show any associations with the risk of SSNHL. These data need to be confirmed on larger series of patients. In conclusion, the IL-6 C − 572G polymorphism is associated with a risk of SSNHL. Because permeability of blood vessels in the inner ear is frequently increased in patients with SSNHL, inflammation of the inner ear might be involved.

Contrast enhancement of the inner ear in magnetic resonance images taken at 10 minutes or 4 hours after intravenous gadolinium injection.

Abstract Conclusion. Contrast enhancement of the inner ear by three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI) taken 4 h after intravenous gadolinium (Gd) injection was better than when taken at 10 min. Using heavily T2-weighted 3D-FLAIR MRI, visualization of endolymphatic hydrops (EH) was possible in the vestibule and the cochlea after a standard intravenous dose of Gd. Objectives. To define a suitable time point for imaging Gd uptake in the inner ear acquired with heavily T2-weighted 3D-FLAIR MRI after standard intravenous Gd administration. Methods: Using a 3 Tesla MRI unit, heavily T2-weighted 3D-FLAIR MRI images were taken twice at approximately 10 min (conventional timing) and 4 h after intravenous gadodiamide (0.1 mmol/kg) injection in 10 patients with inner ear diseases including Ménières disease. Results: The 4 h delay increased Gd enhancement of the 3D-FLAIR MRI images of the perilymphatic space in both symptomatic and asymptomatic ears. The increase in Gd enhancement was greater in symptomatic than in asymptomatic ears. Using this heavily T2-weighted 3D-FLAIR technique, EH was observed in both the cochlea and vestibule in images taken 4 h after the intravenous Gd injection.

Relationship Between Hematotoxicity and Serum Albumin Level in the Treatment of Head and Neck Cancers with Concurrent Chemoradiotherapy Using Cisplatin

OBJECTIVE Patients with locally advanced head and neck cancer were treated with concurrent chemoradiotherapy using three courses of cisplatin. However, many patients were unable to complete the scheduled cisplatin treatment due to adverse effects. The objective of this study was to retrospectively elucidate the source of the low completion rate of cisplatin courses. METHODS Between November 2007 and 28 May 2010, patients with head and neck cancer were treated with curative intent according to the concurrent chemoradiotherapy protocol (66-70 Gy at 2 Gy/day with cisplatin 80 mg/m(2) on Days 1, 22 and 43). Treatment courses, hematological data and other parameters were investigated, and the treatment completion rates and reasons for treatment failure were analyzed. RESULTS Among the 28 patients, cisplatin was administered during the period of radiotherapy a total of 3 times in 9 (32%) patients, 2 times in 15 (54%) patients and only 1 time in 4 (14%) patients. Multiple regression analysis of the development of neutropenia at 3 weeks after the first cisplatin administration revealed that the serum albumin level was a significant explanatory variable (R(2)= 0.664, β = 0.517, P< 0.01). Pearsons product-moment correlation coefficient showed a strong correlation between the serum albumin level and the neutrophil count after 3 weeks (r = 0.605, P< 0.01). CONCLUSIONS The treatment completion rate by this protocol was low in head and neck cancer patients even when the cisplatin dose was reduced to 80 mg/m(2). This tendency was seen in patients with a low serum albumin level.

Effect of clinical symptoms on the indication for selective neck dissection for N0 carcinomas of the parotid gland

Lymph node metastasis is a major prognostic factor in parotid carcinoma, however, the pre-operative diagnosis of occult nodal metastasis is difficult in clinical N0 (cN0) parotid cancer patients. In addition, the indication of neck dissection in T1-3 cN0 patients is controversial. The current study investigated 17 patients with clinical T1-3 cN0 parotid cancer, and analyzed the correlation between patient symptoms/findings and pathological N status/tumor histological grade. In the statistical analysis, pain was found to significantly correlate with neck metastasis. Furthermore, cN0-staged patients without pain exhibited no neck metastasis. However, no significant correlation was identified between patient symptoms or findings and histological grade. These results indicate the possibility that selective neck dissection can be omitted for T1-3 cN0-staged patients without pain.

Craniofacial Resection for T4 Maxillary Sinus Carcinoma Managing Cases with Involvement of the Skull Base

Objective The objective of this study was to clarify the outcomes of craniofacial resection for locally advanced maxillary sinus carcinoma classified as T4 and to present methods for managing cases involving the skull base. Study Design Case series with chart review. Setting Tertiary university hospital. Subjects and Methods We performed anterolateral craniofacial resection in en bloc fashion for locally advanced maxillary sinus carcinoma at stage T4. Participants comprised 40 patients with T4 maxillary sinus carcinoma treated between 1992 and 2011. Surgical outcomes were analyzed retrospectively. Results Forty patients with stage T4a (n = 26) or stage T4b (n = 14) were included in this study. Five-year overall and disease-free survival rates for the 40 patients with T4 maxillary sinus carcinoma were 62.7% and 52.6%, respectively. Cavernous sinus involvement correlated significantly with worse prognosis (P = .012). In 35 cases without cavernous sinus involvement, previous treatment (P = .017) and positive margins (P = .019) correlated significantly with worse prognosis, and 5-year overall and disease-free survival rates were 72.4% and 55.3%, respectively. Conclusion This study only included cases of locally advanced maxillary sinus carcinoma classified as T4. Considering the advanced stage, our study suggests relatively favorable outcomes and the importance of managing the cavernous sinus in en bloc resections of malignant skull base tumors. Craniofacial resection in en bloc fashion achieved good survival rates.

Pharmacokinetic study of S-1 in patients in whom inulin clearance was measured.

Objective: This pharmacokinetic study of S-1 was conducted in patients in whom glomerular filtration rate (GFR) was directly measured to explore the possibility of adjusting the S-1 dose on the basis of GFR in patients with normal or nearly normal renal function. Methods: S-1 was given to 12 patients twice daily for 28 consecutive days followed by 14 days of rest, repeated every 6 weeks. GFR was measured on the basis of inulin clearance (CLin) before the first day of treatment. Results: The area under the time-concentration curve (AUC) of 5-fluorouracil (5-FU) correlated with that of 5-chloro-2,4-dihydroxypyridine (CDHP, r = 0.750, p = 0.005). The AUC of CDHP correlated with the measured 24-hour creatinine clearance (CLcr) per subject (r = –0.620, p = 0.032), but not with the CLin (r = –0.356, p = 0.257). The AUC of 5-FU did not correlate with either the 24-hour CLcr per subject (r = –0.401, p = 0.187) or with the CLin (r = –0.300, p = 0.351). Conclusion: Dosage adjustment based on the GFR does not reduce individual variations in 5-FU concentrations among patients with normal or nearly normal renal function who receive S-1.

Salvage pharyngolaryngectomy with total esophagectomy following definitive chemoradiotherapy

Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high-dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short-term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.

Endothelin-1 gene polymorphism in sudden sensorineural hearing loss

Endothelin‐1 is a potent vasoconstrictor peptide that is widely distributed throughout the mammalian body including the spiral modiolar artery, vestibule, and cochlea. This study aimed to investigate the association between the Lys198Asn (G/T) polymorphism (rs5370) of the endothelin‐1 gene and sudden sensorineural hearing loss (SSNHL).

Computed tomographic assessment of autologous fat injection augmentation for vocal fold paralysis: CT of Autologous Fat Injection Augmentation

To perform a quantitative computed tomography (CT) assessment of short‐ and long‐term outcomes of autologous fat injection augmentation in patients with unilateral vocal fold paralysis.