Publications by authors named "Masao Yagi"

27 Publications

  • Page 1 of 1

Utility of an immunocytochemical analysis for pan-Trk in the cytodiagnosis of secretory carcinoma of the salivary gland.

Diagn Cytopathol 2021 Aug 22;49(8):E329-E335. Epub 2021 Apr 22.

Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka, Japan.

Secretory carcinoma (SC) of the salivary gland is a rare distinct clinicopathological entity characterized by the presence of the ETV6-NTRK3 fusion. Although the characteristic cytological features of SC have been recognized, its cytodiagnosis, especially differentiating SC from acinic cell carcinoma, is challenging. Recent studies have revealed that immunohistochemistry for pan-tyrosine receptor kinase (Trk) and nuclear receptor subfamily 4 group member 3 (NR4A3) are specific for SC and acinic cell carcinoma, respectively. However, the usefulness of immunocytochemical detection of these markers in the diagnosis of SC has not been addressed. Hence, the present study aimed to analyze the usefulness of immunocytochemical staining for pan-Trk and NR4A3 in the cytodiagnosis of SC. We enrolled eight patients with a histopathological diagnosis of SC who underwent preoperative fine-needle aspiration cytological examination. The cytological characteristics were reviewed and immunocytochemical staining for pan-Trk and NR4A3 was performed. The characteristic cytological features noted in the patient cohort included neoplastic cell clusters with a sheet-like and papillary cluster arrangement as well as single cells. Additionally, neoplastic cells with mild to moderately enlarged nuclei and small nucleoli, multi-vacuolated cytoplasm, and intracytoplasmic mucin were also observed. The immunocytochemical analyses clearly demonstrated that all eight specimens showed positive nuclear staining for pan-Trk, but were negative for NR4A3 expression. Although all cases of SC do not always show positive immunoreactivity for pan-Trk, immunocytochemical analysis for pan-Trk may be useful for the cytodiagnosis of SC along with assessment of the characteristic cytological features.
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http://dx.doi.org/10.1002/dc.24750DOI Listing
August 2021

Identification of risk factors for mortality and delayed oral dietary intake in patients with open drainage due to deep neck infections: Nationwide study using a Japanese inpatient database.

Head Neck 2021 07 2;43(7):2002-2012. Epub 2021 Mar 2.

Department of Otolaryngology Head and Neck Surgery, Kansai Medical University, Hirakata, Japan.

Backgrounds: Data on risk factors for deep neck infection including descending necrotizing mediastinitis (DNM) have been limited. Using a nationwide database, the aim was identifying the factors related to patient death and delay in recovering oral intake.

Methods: Data of 4949 patients were extracted from a Japanese inpatient database between 2012 and 2017. The main outcome was survival at discharge. In a subgroup analysis of the 4949 patients with survival, the second outcome was delay in the interval between admission and full recovery of oral intake.

Results: Only a few factors (advanced-age, ventilation) were associated with both mortality and delayed oral dietary intake by logistic regression analyses. Conversely, several factors including DNM (adjusted-odds ratio [OR] 1.41) and repeated surgery (adjusted-OR 1.70) were significantly related only to delayed oral dietary intake.

Conclusions: Although DNM was not necessarily related to mortality, patients with DNM should receive careful attention to avoid delayed oral dietary intake.
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http://dx.doi.org/10.1002/hed.26660DOI Listing
July 2021

Early voice therapy for unilateral vocal fold paralysis improves subglottal pressure and glottal closure.

Am J Otolaryngol 2020 Nov - Dec;41(6):102727. Epub 2020 Sep 13.

Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka 573-1010, Japan.

Purpose: In cases of unilateral vocal fold paralysis (UVFP), voice disorders caused by glottic insufficiency can lead to a considerable reduction in the patient's quality of life. Voice therapy (VT) is an effective treatment that must be started early after the onset of vocal fold paralysis. This study examined the effect of early VT for patients with UVFP occurring after esophagectomy.

Materials And Methods: Patients who had residual UVFP at 1 month postoperatively after esophagectomy for esophageal cancer between November 2014 and March 2017 were evaluated. Seventeen patients were divided into the VT group (n = 6) and non-VT group (n = 11). We compared these two groups and retrospectively examined the effect of early VT. The study endpoints included aerodynamic tests, laryngeal endoscopy, laryngeal stroboscopy, and glottal closure. All of these evaluations were performed at preoperatively and at 1 and 3 months postoperatively.

Results: Subglottal pressure reduced notably in the VT group, and both the mean flow rate and maximum phonation time tended to improve after VT. Conversely, there were no significant differences in MFR and MPT in the non-VT group. Furthermore, although UVFP remained after VT, we achieved glottal closure for all three patients. Conversely, only two of the six patients with glottic insufficiency in the non-VT group achieved glottal closure.

Conclusion: VT may be effective for improving impaired vocal function in patients with UVFP. It is reasonable to expect that VT can be initiated 1 month after the onset of vocal fold paralysis.
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http://dx.doi.org/10.1016/j.amjoto.2020.102727DOI Listing
December 2020

Increased CD69 expression on activated eosinophils in eosinophilic chronic rhinosinusitis correlates with clinical findings.

Allergol Int 2020 Apr 10;69(2):232-238. Epub 2020 Jan 10.

Department of Otorhinolaryngology, Head & Neck Surgery, Kansai Medical University, Osaka, Japan.

Background: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis associated with asthma. CD69 is an important marker of activation for eosinophils. But, whether a correlation exist between the CD69 expression on eosinophils and clinical findings is unclear.

Methods: We performed quantitative PCR and/or flow cytometry using tissue and purified eosinophils from the blood and nasal polyps of 12 patients with ECRS and from 8 patients without ECRS (controls). We assessed clinical findings including nasal polyp (NP) scores, sinus CT findings, and pulmonary function test results, and examined their possible association with the CD69 expression. We also performed CD69 cross-linking experiments in mouse eosinophils to investigate the functional role of CD69.

Results: Levels of cytokine mRNAs (IL-4, -5, -10, and -13) were significantly higher in purified NP eosinophils and tissues from patients with ECRS than the levels of those in controls. The expressions of major basic protein (MBP), eosinophilic cationic protein (ECP), eosinophilic-derived neurotoxin (EDN), eosinophil peroxidase (EPX) in cytotoxic granules, and CD69 mRNA were significantly higher in purified eosinophils from NPs than in those from blood. We also found a correlation between expression of CD69 and clinical findings. Moreover, we found EPX release from mouse eosinophils following CD69 cross-linking.

Conclusions: These data suggest that increased CD69 expression by eosinophils is not only a biomarker for nasal obstruction and pulmonary dysfunction, but also a potential therapeutic target for patients with ECRS and asthma.
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http://dx.doi.org/10.1016/j.alit.2019.11.002DOI Listing
April 2020

Quantitative immunohistochemical assay with novel digital immunostaining for comparisons of PD-L1 antibodies.

Mol Clin Oncol 2019 Mar 17;10(3):391-396. Epub 2019 Jan 17.

Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Osaka 573-1010, Japan.

One obstacle in diagnostic pathology is the harmonization of one drug-one diagnostic tests for programmed death ligand-1 (PD-L1). There are many challenges in accurate comparisons of diagnostic tests, such as differences in the titer of each antibody, detection system and dynamic range of visualization. Our previously developed digital immunostaining technique is highly sensitive and quantitative with the ability to quantify particles that bind in a one-to-one fashion with antibody in each cell. Determining the differences in the titer of each antibody with digital immunostaining may be beneficial for future harmonized analysis. To demonstrate the accuracy of digital immunostaining, the present study compared the number of particles with ELISA and nCounter data from five cell lines. NCI-H460 exhib-ited the highest level of PD-L1 protein, followed by A549, PC-3, NCI-H1299, and NCI-H446 cells. In addition, the PD-L1 mRNA values determined by nCounter corresponded with the order of the protein levels determined by ELISA. The present study revealed that digital immunostaining for PD-L1 was highly associated with ELISA and nCounter data. Among the four antibodies tested, the titer of all but SP142 coincided with ELISA and nCounter data. These results indicated that our digital immunostaining technique may be beneficial for future harmonized analysis.
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http://dx.doi.org/10.3892/mco.2019.1801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388504PMC
March 2019

A comparison of short-term outcomes of neck dissection for head and neck cancers using Thunderbeat™, LigaSure™ or treatment without an energy-based device: A case controlled study.

Int J Surg 2018 Oct 21;58:60-64. Epub 2018 Sep 21.

Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University Hospital, Japan.

Objective: The aim of this study was to evaluate the efficacy of the new energy-based device Thunderbeat in neck dissection (ND) for head and neck cancer.

Materials And Methods: We retrospectively examined 95 consecutive patients who underwent ND for head and neck squamous cell carcinoma between April 2013 and March 2018. The patients were divided into three groups: ND without the energy-based device (control group), ND using the LigaSure Small Jaw (LS group), and ND using the Thunderbeat Open Fine Jaw (TB group). The outcomes were compared among the three groups, as measured by the duration of ND (dissection time), blood loss during ND, and postoperative complications. We also analyzed the factors that may influence dissection time using multivariate analysis.

Results: Compared to the control group, dissection time was found to be significantly shorter in both energy-based device groups (LS group and TB group) (96.4, 71.1, and 66.0 min, respectively, p = 0.0015) by univariate analysis. Blood loss during ND did not differ significantly among the three groups. Multivariate analysis showed that ND using the Thunderbeat as well as elderly patients (70 years and over), less extensive surgery (3 or fewer neck levels), and absence of extracapsular invasion were independently and significantly associated with shorter dissection time (p = 0.0069, 0.0337, <0.0001, and 0.0015, respectively). The incidence of postoperative complications in the LS group (20%) tended to be higher than those in the other groups (5.6% in the control group and 3.4% in the TB group), although the differences were not significant.

Conclusion: ND for head and neck cancers using the Thunderbeat is a safe and reliable method in terms of duration of dissection without increasing postoperative complications.
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http://dx.doi.org/10.1016/j.ijsu.2018.09.009DOI Listing
October 2018

Residual Recurrent Nerve Paralysis After Esophagectomy is Associated with Preoperative Lower Serum Albumin.

Dysphagia 2017 08 24;32(4):520-525. Epub 2017 Apr 24.

Department of Otolaryngology Head & Neck Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.

Esophagectomy for esophageal cancer is invasive thoracic surgery with a high incidence rate of postoperative complications and prolongation of hospitalization, even if the standardized clinical pathway improves the outcome (mortality and morbidity). Postoperative recurrent nerve paralysis (RNP) is related to respiratory complications concomitant with prolonged hospitalization. However, it has not been elucidated which factors affect the incidence and recovery of RNP. To detect the predictive factor for postoperative RNP, we focused on preoperative serum albumin. Patients who had esophageal cancer with standard esophagectomy were evaluated. In total, 94 patients were divided into three groups depending on the presence of RNP (46 in patients without RNP, 29 in those with transient RNP who recovered within 6 months follow-up and 19 in those with residual RNP). We retrospectively investigated factors associated with residual RNP. Preoperative lower serum albumin was associated with residual RNP. In addition, days to the resumption of oral intake and duration of stay in the hospita postoperatively were delayed in the group of residual RNP. Multiple regression analysis indicated that preoperative serum albumin was a predictive factor for residual RNP. Preoperative lower serum albumin level might be linked to residual RNP which could prolong the resumption of postoperative oral intake and shorten the period of stay at the hospital after esophagectomy, leading to unfavorable outcomes for patients.
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http://dx.doi.org/10.1007/s00455-017-9793-3DOI Listing
August 2017

Mammary Analogue Secretory Carcinoma Presenting as a Cervical Lymph Node Metastasis of Unknown Primary Site: A Case Report.

Case Rep Oncol 2017 Jan-Apr;10(1):192-198. Epub 2017 Feb 15.

Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University Hospital, Hirakata, Japan.

Background: Mammary analogue secretory carcinoma (MASC) is a pathological entity arising in the salivary glands first described by Skalova et al. [Am J Surg Pathol 2010;34: 599-608]. Here, we report the first case of MASC presenting as a cervical lymph node metastasis of unknown primary site together with a brief review of the literature.

Case Report: We present a 74-year-old male with a painless lump in his left neck. Based on the fine-needle aspiration cytological findings, a possible malignant tumor was suspected. No evidence of a primary lesion was observed using imaging modalities including positron emission tomography/computed tomography. The patient underwent an ipsilateral modified radical neck dissection. Immunohistochemical staining showed that the neoplastic cells were positive for S100 protein and GATA3. A rearrangement of the ETV6 gene was noted during fluorescence in situ hybridization, and the final histopathological diagnosis was MASC.

Conclusion: We encountered a MASC presenting as a cervical lymph node metastasis of unknown primary site. No adjuvant therapy was administered, and no local recurrence or metastatic disease has been detected during a follow-up period of 9 months. This is the first case report of MASC presenting as a cervical lymph node metastasis of unknown primary site and suggests the new properties of MASC.
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http://dx.doi.org/10.1159/000457949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346937PMC
February 2017

[A Clinical Study on Cervical Tuberculous Lymphadenitis].

Nihon Jibiinkoka Gakkai Kaiho 2015 May;118(5):643-50

We retrospectively examined the records of patients treated for cervical tuberculous lymphadenitis in our department and analyzed the effectiveness of the various diagnostic methods. From January 2006 to December 2013, we treated 19 cases of cervical tuberculous lymphadenitis. The ages of patients with cervical tuberculous lymphadenitis ranged from 28 to 87 years old (mean, 61.4 years), and the male-to-female ratio was 8: 11. Two of the 19 patients with cervical tuberculous lymphadenitis presented with the comorbid condition of pulmonary tuberculosis. The sensitivity of cytological examination, smears, cultures and PCR (polymerase chain reaction) technique using an aspiration procedure for cervical tuberculous lymphadenitis were 13.3%, 50%, 60% and 71.4%, respectively: Although the detection ratio of fine needle aspiration cytology alone was low, the aspiration procedure could permit a definitive diagnosis by a combination of smear, culture and PCR. The QuantiFERON test (QFT) was positive in seven of seven cases, and T-SPOT was positive in two of two cases. Thus, QFT and T-SPOT were useful as aids in the diagnosis of cervical tuberculous lymphadenitis. For early diagnosis of cervical tuberculous lymphadenitis, it is important to consider a combined multimodal approach.
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http://dx.doi.org/10.3950/jibiinkoka.118.643DOI Listing
May 2015

[The present status of CapeOX as adjuvant chemotherapy for colorectal cancer].

Gan To Kagaku Ryoho 2015 Mar;42(3):319-22

Dept. of Surgery, Public Central Hospital of Matto Ishikawa.

We report on treatment with capecitabine plus oxaliplatin (CapeOX) as adjuvant therapy for patients with colorectal cancer. Twenty patients were treated. The mean age was 69 years; 15 patients were male and 5 were female. Thirteen patients with colon cancer and 7 patients with rectal cancer were enrolled after curative surgery. In total, 55% of patients completed the planned number of treatment cycles. Dose modifications were required for oxaliplatin in 60% of patients and for capecitabine in 67% of patients. The median relative dose intensities of oxaliplatin and capecitabine were 86% and 88%, respectively. Treatment-related Grade 3/4 neutropenia and Grade 3/4 thrombocytopenia were documented in 2 and 3 patients, respectively. Grade 3/4 hand-foot syndrome occurred in 1 patient. Treatment with CapeOX as adjuvant therapy for patients with colorectal cancer seems to be safe.
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March 2015

[Our experience with panitumumab used for patients with metastatic colorectal cancer].

Gan To Kagaku Ryoho 2013 Jan;40(1):67-9

Dept. of Surgery, Public Central Hospital of Matto Ishikawa, Japan.

We report having treated patients with metastatic colorectal cancer with panitumumab in our department. Ten patients were treated. The mean age was 65. 7 years-old with 7 males and 3 females. Seven patients were treated with only panitumumab, and three patients were treated with panitumumab and another drug. The median number of infusions was 8 times. In the 9 cases that could be evaluated, the disease control rate was 66. 6%. Skin toxicity was observed in all patients. A low serum magnesium value of grade 3 was observed in one patient. We consider that treatment with panitumumab for patients with metastatic colorectal cancer was a safe option.
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January 2013

Characterization of side population (SP) cells in murine cochlear nucleus.

Acta Otolaryngol 2012 Jul 5;132(7):693-701. Epub 2012 Jun 5.

Regeneration Research Center for Intractable Diseases, Kansai Medical University, Osaka, Japan.

Conclusion: We characterized side population (SP) cells in the cochlear nucleus (CN). Some genes of stem/progenitor markers in sorted SP cells were identified by microarray analysis and RT-PCR. Furthermore, some cells in the CN also demonstrated self-renewal and clonal expansion activities. These results suggest that tissue stem/ progenitor like cells would be identified and characterized as a slow cycling and immaturity in SP cells of CN.

Objectives: SP cells were sorted and characterized as regards their activity in the CN in order to identify the tissue progenitor/stem cells in the auditory nervous system.

Methods: Bromodeoxyuridine (BrdU)-injected mice were prepared and the long-term BrdU-retaining cells were detected by flow cytometry. Gene expression of SP and MP cells was analyzed by microarray analysis and RT-PCR. SP cells were cultured in conditioned medium to expand stem/progenitor cells in vitro and to estimate the spheroid-forming activity of stem cells.

Results: In all, 1% of cells in the CN were detected as BrdU-positive. SP cells were detected at a frequency of 4.4% and expressed stem/progenitor markers, Abcb1b, Abcg2, Sca1, Notch1, Notch4, Hes1, and Jag1 in microarray analysis. Expression of Abcb1b, Abcg2, Sca1,Oct3/4, and Sox2 as determined by RT-PCR was supported by the microarray data. CN cells also had sphere-forming activity in young mice, but this activity was decreased by aging.
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http://dx.doi.org/10.3109/00016489.2012.657358DOI Listing
July 2012

Downregulation of N-methyl-D-aspartate receptor ζ1 subunit (GluN1) gene in inferior colliculus with aging.

Brain Res 2012 May 14;1454:23-32. Epub 2012 Mar 14.

Department of Otolaryngology, Kansai Medical University, Takii Hospital, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.

Presbycusis is the impairment of auditory function associated with aging, which stems from peripheral cochlear lesions and degeneration of the central auditory process. The effect of age-induced peripheral hearing loss on the central auditory process is not fully understood. C57Bl/6 (C57) mice present accelerated peripheral hearing loss, which is well developed by middle-age and mimics the human presbycusis pattern. The aim of this study was to elucidate the molecular effects of peripheral hearing loss in the inferior colliculus (IC) with age between young and middle-aged C57 mice using cDNA microarray. Glutamate receptor ionotropic NMDA ζ1 (GluN1) exhibited the greatest decrease in the middle-aged group as determined using cDNA microarray and by further assessment using real-time PCR (qPCR). Histological assessment with in situ hybridization of GluN1 showed significantly decreased expression in all IC subdivisions of the middle-aged group. GluN1 is a receptor for excitatory neurotransmission, and significant downregulation of this gene may be subsequent to the decline of afferent input from the cochlea in aging C57 mice. Consequently, using the combination of microarray, qPCR, and in situ hybridization, we showed that the decline of GluN1 in the IC of aging animals might have a key role in the pathogenesis of presbycusis.
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http://dx.doi.org/10.1016/j.brainres.2012.03.018DOI Listing
May 2012

[Provision for adverse effect of S-1 containing chemotherapy in patients with advanced digestive cancer--combination with superfine dispersed lentinan].

Gan To Kagaku Ryoho 2010 Mar;37(3):457-62

Medical and Food Conference for Gastroenterology, Affiliated Organization of Japanese Academic Conference for Advanced Age Gastroenterology.

Purpose: Recently, in drug therapy for patients with advanced digestive cancer, S-1 (tegafur x gimeracil x oteracil potassium) alone or S-1 combined with other chemotherapeutic agents (S-1+alpha) is prescribed. However, many patients are often forced to give up long-term S-1 treatment owing to high incidence rates of adverse effects. The purpose of this study was to evaluate the efficacy of superfine dispersed lentinan (SDL) for the suppression of adverse effects of S-1 or S-1+alpha.

Subjects And Method: The subjects were 72 patients who had unresectable or recurrent advanced digestive cancer. The subject group consisted of 45 men and 27 women, with a median age of 64 (31-85) years; 29 gastric, 25 colorectal, 10 pancreatic and 8 other digestive cancer patients. Thirty -one patients were administered S-1 alone and 41 patients were administered S-1+alpha. SDL (15mg of lentinan/bag/day) was orally administered to all patients for 12 weeks. Adverse events and overall survival time were evaluated according to the CTCAE ver 3.0 and the Kaplan-Meier method, respectively.

Results: Seventy-two patients were enrolled in this study. Adverse events which had an undeniable causal relationship to SDL were observed in 2 patients (2.7 %, constipation [Grade 2] and nausea [Grade 1]) out of 72 patients; all of the events were not severe and disappeared when the SDL administration was discontinued. Adverse events associated with S-1 or S-1+ alpha were observed in 9 patients (12.5% ) (11 events) out of 72 patients. Grade 3 adverse events were observed in 3 patients (4.2% ) (leukopenia, 2; thrombocytopenia, 1). Incidence rates of both hematological and nonhematological adverse events were very low. In no gastrointestinal toxicity associated with S-1 or S-1+alpha was observed, which was estimated to be an effect of SDL combination. Mean survival times in gastric cancer and colorectal cancer patients were 9. 5 months (95%confidential interval [CI], 7.0-22.4 months) and 18.4 months (95% CI, 13.2 -28.5 months), respectively.

Conclusions: From the results of the present study, SDL is considered completely free of anything harmful to advanced digestive cancer patients and is effective for the suppression of adverse effects of S-1 or S-1+alpha therapy. It is suggested that SDL can prolong the administration period of S-1 and, as a result, contribute to prolongation of survival in patients with advanced digestive cancer.
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March 2010

[A case report: multiple air embolism after the laryngopharyngoesophagectomy occurred by the cervical infection from postoperative fistula].

Nihon Jibiinkoka Gakkai Kaiho 2010 Jan;113(1):20-5

Kansai Medical University, Otorhinolaryngology-Head and Neck Surgery, Hirakata.

Systemic air embolism, a very rare clinical condition, has many causes. We report a case of multiple air embolisms following laryngopharyngoesophagectomy salvage surgery for hypopharyngeal residual cancer after concurrent chemoradiotherapy. Cervical infection arose from a fistula caused by postoperative suture failure in which the 56-year-old man suddenly lost consciousness and went into shock. A few days post operation, an air embolism happened and caused in the brain, pulmonary, myocardiac and cerebral infarction. The man died two months after initial occurrence. We suspect that air entered through the ruptured left internal jugular vein via infection due to aspiration at the injury site. Air embolisms are associated with different medical maneuvers, and it is necessary to recognize that they may become a serious perioperative complication.
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http://dx.doi.org/10.3950/jibiinkoka.113.20DOI Listing
January 2010

[Clinical study of adenoid cystic carcinoma of the parotid gland].

Nihon Jibiinkoka Gakkai Kaiho 2007 May;110(5):410-5

Department of Otolaryngology, Osaka Saiseikai-Izuo Hospital, Osaka.

We report results of a retrospective study of 12 cases of adenoid cystic carcinoma (ACC) in the parotid gland. Local pain was often observed in ACC among other malignant parotid tumors. Although fine-needle aspiration cytology (FNA) was not effective for preoperative diagnosis, frozen section diagnosis (FS) during surgery showed excellent results. Cases with T3 or T4 underwent total or enlarged parotidectomy, but, often showed positive surgical margins. Postoperative radiation therapy seemed useful in these cases and the 5-and 10-year disease-specific survivals in these 12 cases were 90.0% and 80.8%. These compare favorably with other reports in the literature. All 12 cases showed NO and no cervical relapse with or without neck dissection, indicating little effectiveness in prophylactic neck dissection. Tumor size, positive surgical margins, and perineural invasion are risk factors for this tumor as mention previously. Patients with perineural invasion, especially preoperative facial nerve palsy (T4a), are more likely to fail than those with two other factors, so, it seems conceivable for cases of T4a to undergo more positive treatment with surgery and postoperative radiation.
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http://dx.doi.org/10.3950/jibiinkoka.110.410DOI Listing
May 2007

Administration of amitriptyline attenuates noise-induced hearing loss via glial cell line-derived neurotrophic factor (GDNF) induction.

Brain Res 2007 May 31;1144:74-81. Epub 2007 Jan 31.

Department of Otolaryngology, Kansai Medical University Takii Hospital, 10-15 Fumizonocho Moriguchi-shi, Osaka 570-8507, Japan.

Antidepressant treatments have been described to induce neurotrophic factors (NTFs) and reverse the cell loss observed in rodent stress models. Amitriptyline (AT), a tricyclic antidepressant agent, has been reported in recent studies to induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells. GDNF has shown protection against acoustic trauma in previous studies. Therefore, we investigated whether AT could induce GDNF synthesis in the cochlea and attenuate cochlea damage against acoustic trauma. We used Hartley guinea pigs and injected AT (30 mg/kg) or saline into the peritoneum. Subjects were exposed to 117 dB SPL octave band noise centered at 4 kHz for 24 h. Noise-induced hearing loss (NIHL) was assessed with auditory brain stem response (ABR) at 4, 8 and 16 kHz measured prior to the injection, 3 days and 7 days after noise exposure. For histological assessment, we observed the sensory epithelium using a surface preparation technique and assessed the quantitative hair cell (HC) damage. We evaluated GDNF synthesis with or without intense noise exposure at 3, 12 and 24 h after the administration of AT in the cochlea using Western blot analysis. GDNF expression was shown 3 h and 12 h after the injection without noise, whereas with noise the GDNF expression lasted for 24 h. The AT-administrated group showed significantly reduced ABR threshold shift and less HC damage than the saline-administrated group. These findings suggest that the administration of AT-induced GDNF levels in the cochlea and attenuated cochlea damage from NIHL.
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http://dx.doi.org/10.1016/j.brainres.2007.01.090DOI Listing
May 2007

Case report of an obturator hernia diagnosed by an orthopedist.

J Orthop Sci 2005 May;10(3):321-3

Department of General Surgery, Mattou Ishikawa Central Hospital, 3-8 Kuramitsu, Mattou, Ishikawa, 924-8588, Japan.

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http://dx.doi.org/10.1007/s00776-005-0886-8DOI Listing
May 2005

Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in guinea pig.

Hear Res 2004 Oct;196(1-2):58-68

Department of Otolaryngology, Kansai Medical University, Fumizono-cho 10-15, Moriguchi, Osaka 570-8507, Japan.

The protective effect of dexamethasone (DEX) against noise-induced trauma, as reflected in hair cell destruction and elevation in auditory brainstem response (ABR) sensitivity, was assessed in guinea pigs. The animals were administered DEX (1, 10, 100, and 1000 ng/ml) or artificial perilymph (AP) via a mini-osmotic pump directly into scala tympani and, on the fourth day after pump implantation, exposed to 120 dB SPL octave band noise, centered at 4 kHz, for 24 h. Animals receiving DEX demonstrated a dose-dependent reduction in noise-induced outer hair cell loss (significant at 1, 10 and 100 ng/ml DEX animals compared to AP control animals) and a similar attenuation of the noise-induced ABR threshold shifts, observed 7 days following exposure (significant at 100 ng/ml DEX animals compared to AP control animals). These physiological and morphological results indicate that direct infusion of DEX into the perilymphatic space has protective effects against noise-induced trauma in the guinea pig cochlea.
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http://dx.doi.org/10.1016/j.heares.2004.06.003DOI Listing
October 2004

Chronic excitotoxicity in the guinea pig cochlea induces temporary functional deficits without disrupting otoacoustic emissions.

J Acoust Soc Am 2004 Aug;116(2):1044-56

Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0506, USA.

Brief cochlear excitotoxicity produces temporary neural swelling and transient deficits in auditory sensitivity; however, the consequences of long-lasting excitotoxic insult have not been tested. Chronic intra-cochlear infusion of the glutamate agonist AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) resulted in functional deficits in the sound-evoked auditory brainstem response, as well as in behavioral measures of hearing. The electrophysiological deficits were similar to those observed following acute infusion of AMPA into the cochlea; however, the concentration-response curve was significantly shifted as a consequence of the slower infusion rate used with chronic cochlear administration. As observed following acute excitotoxic insult, complete functional recovery was evident within 7 days of discontinuing the AMPA infusion. Distortion product otoacoustic emissions were not affected by chronic AMPA infusion, suggesting that trauma to outer hair cells did not contribute to AMPA-induced deficits in acoustic sensitivity. Results from the current experiment address the permanence of deficits induced by chronic (14 day) excitotoxic insult as well as deficits in psychophysical detection of longer duration acoustic signals.
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http://dx.doi.org/10.1121/1.1772395DOI Listing
August 2004

Hearing and hair cells are protected by adenoviral gene therapy with TGF-beta1 and GDNF.

Mol Ther 2003 Apr;7(4):484-92

Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, The University of Michigan, Ann Arbor, Michigan 48109-0648, USA.

Glial cell line-derived neurotrophic factor (GDNF) overexpression in the inner ear can protect hair cells against degeneration induced by aminoglycoside ototoxicity. The protective efficiency of GDNF increases when it is combined with co-factors such as transforming growth factor beta1 (TGF-beta1), a ubiquitous cytokine. The aim of this study was to determine whether TGF-beta1 receptors are expressed in the inner ear and whether a cocktail of GDNF and TGF-beta1 transgenes provides enhanced protection of the inner ear against ototoxic trauma. Using RT-PCR analysis, we determined that both TGF-beta1 receptors, type 1 and 2 are present in rat cochlea. We co-inoculated two adenoviral vectors, one encoding human TGF-beta1 gene (Ad.TGF-beta1) and the other encoding human GDNF gene (Ad.GDNF) into guinea pig cochleae 4 days prior to injecting an ototoxic dose of aminoglycosides. Inoculated ears had better hearing and fewer missing inner hair cells after exposure to the aminoglycoside ototoxicity, as compared with controls and ears treated only with Ad.GDNF. Cochleae with TGF-beta1 overexpression exhibited fibrosis in the scala tympani regardless of the presence of GDNF. Our results suggest that the adenovirus-mediated overexpression of GDNF and TGF-beta1 can be used in combination to protect cochlear hair cells and hearing from ototoxic trauma.
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http://dx.doi.org/10.1016/s1525-0016(03)00058-3DOI Listing
April 2003

Gene-based therapy for inner ear disease.

Noise Health 2001 ;3(11):37-47

Kresge Hearing Research Institute, The University of Michigan Medical School, Ann Arbor, MI 48109-0648, USA.

Environmental inner ear insults often lead to hair cell injury and loss. Therapeutic measures for the prevention of hair cell loss are currently limited. Several reports have demonstrated the applicability of growth factors for hair cell protection. The goal of the experiments presented here was to assess the protective capability of the human GDNF transgene against noise trauma in the guinea pig cochlea. The left ears of guinea pigs were inoculated with a recombinant adenovirus with a human GDNF insert (Ad.GDNF). Four days later, animals were exposed to noise trauma. One week later, animals were sacrificed and hair cells counted in the left (inoculated) and right (non-inoculated) ears. Auditory brainstem thresholds were measured before the inoculation and just prior to sacrifice. Control groups included inoculation with a reporter gene vector (Ad.lacZ) and Ad.GDNF in normal ears with no noise exposure. The results show that intracochlear inoculation with adenovirus into normal ears does not compromise hair cell counts and ABR thresholds. Both Ad.GDNF and Ad.lacZ vectors can protect the cochlear hair cells and hearing from the noise insult. The difference between the protection afforded by Ad.GDNF and that of the Ad.lacZ vector is not statistically significant. The mechanism of Ad.lacZ protection needs to be elucidated. The data demonstrate the general feasibility of gene therapy for over-expression of neurotrophic factors against noise trauma, and emphasize the complexity of the technique and the problems of variability between subjects.
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January 2001

Regeneration of small intestinal mucosa after acute ischemia-reperfusion injury.

Dig Dis Sci 2002 Dec;47(12):2704-10

Department of Surgery (II), School of Medicine, Kanazawa University, Ishikawa 920-8641, Japan.

To determine whether c-Fos and c-Jun are involved in the repair of small intestinal mucosa after ischemia-reperfusion (I/R), we investigated the mechanism of regeneration following acute I/R injury in rats by evaluating changes in DNA synthesis, fractional synthesis rate (FSR) of proteins, and alkaline phosphatase (ALP) activity. Furthermore, we examined the sequential expression of c-Fos and c-Jun using western blot analysis and immunohistochemical staining. Proliferating cell nuclear antigen (PCNA) labeling index (LI) demonstrated that the LI of the I/R group at 2 and 6 hr after reperfusion was significantly higher than that of the controls. Statistically significant differences were found between the FSRs of the I/R group and the corresponding conventional group at 2, 6, and 12 hr. The expression of c-Fos and c-Jun proteins increased markedly after I/R and these proteins decreased with time. The levels of ALP in the I/R group were significantly decreased at 2 and 6 hr after reperfusion compared to controls. These results indicate that c-Fos and c-Jun play a central role in the repair process that results in complete restoration of intestinal mucosal function after I/R.
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http://dx.doi.org/10.1023/a:1021049004188DOI Listing
December 2002

[A trial of continuous and biweekly low-dose cisplatin and 5-FU with UFT chemotherapy for esophageal cancer].

Gan To Kagaku Ryoho 2002 Oct;29(10):1809-15

Dept. of Surgery, Public Central Hospital of Mattoh Ishikawa.

A 77-year-old man with advanced esophageal cancer with tracheal and esophageal obstruction underwent continuous low-dose FP chemotherapy for a total of seven weeks, resulting in a complete response (CR) and disappearance of the esophago-tracheal fistula. Since discharge from the hospital, he has maintained a stable good condition for about two years while receiving biweekly low dose FP chemotherapy and oral UFT. Eight patients who had post-operative recurrence and underwent noncurative operation for esophageal cancer were given low-dose FP chemotherapy. The results of this chemotherapy for those 8 patients and the present patient, for a total of 9 patients were 2 CR, 2 PR, 3 NC and 2 PD, with an overall response rate of 44%, and overall one-year and two-year survival rates of 44% and 22%, respectively.
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October 2002

Intra-cochlear administration of dexamethasone attenuates aminoglycoside ototoxicity in the guinea pig.

Hear Res 2002 May;167(1-2):61-70

Department of Otolaryngology, Kansai Medical University, Fumizono-cho 10-15, Moriguchi, Osaka 570-8506, Japan.

This study demonstrates the attenuation of aminoglycoside ototoxicity by cochlear infusion of dexamethasone (Dex) using a microcannulation-osmotic pump delivery system. The results indicate that treating the cochlea with Dex both before and after kanamycin administration was more effective in preventing ototoxicity than Dex treatment only after kanamycin administration. A concentration of 1 ng/ml Dex showed the greatest protective effect on both kanamycin-induced threshold shift of the auditory brainstem response and outer hair cell survival. These results show that the Dex treatment attenuates both functional and structural damage of the inner ear from aminoglycoside toxicity.
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http://dx.doi.org/10.1016/s0378-5955(02)00345-3DOI Listing
May 2002

From gene identification to gene therapy.

Audiol Neurootol 2002 May-Jun;7(3):161-4

Kresge Hearing Research Institute, Ann Arbor, Mich., USA.

Inner ear disease due to hair cell loss is common, and no restorative treatments for the balance and hearing impairment are currently available. To develop clinical means for enhancing protection and regeneration in the inner ear, it is necessary to understand the molecular basis for hereditary and acquired deafness and vestibular disorders. One approach is to identify and characterize genes that regulate protection or repair in other systems. For that purpose, we have used the differential display assay and compared gene expression between normal and acoustically traumatized inner ears of chicks. Several chick cDNAs that were identified are considered as candidates for roles in the reparative process that follows trauma in the basilar papilla. The mammalian vestibular epithelium has a limited regenerative capability. To identify genes that may participate in the regenerative response, we have used gene arrays profiling, comparing normal to drug-traumatized vestibular epithelia. We identified several genes that are differentially expressed in traumatized vestibular epithelium, including several insulin-like growth factor-I binding proteins. To use this molecular knowledge for enhancing protection and repair in the organ of Corti, it is necessary to overexpress the genes of choice in the inner ear. Using viral-mediated gene transfer, we overexpressed transgenic glial cell line-derived neurotrophic factor and demonstrated a robust protective effect against acoustic and ototoxic inner ear trauma. Future identification of the genes that are important for protection and regeneration, along with improved gene transfer technology, will allow the use of gene therapy for treating hereditary and environmental inner ear disease.
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http://dx.doi.org/10.1159/000058303DOI Listing
August 2002
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