PubMed | National Kyushu Cancer Center, Sumitomo Besshi Hospital, Kouseiren Takaoka Hospital, Kyushu University and 6 more.
Type: Journal Article | Journal: Histopathology | Year: 2016
Angiofibroma of soft tissue (AFST) is a rare soft tissue neoplasm characterized by a fibroblastic cytomorphology and a prominent vascular structure. AFSTs possess a novel fusion gene, i.e. NCOA2-AHRR/AHRR-NCOA2 or GTF2I-NCOA2, providing a useful approach to diagnosing AFST. Morphologically, AFSTs span a wide spectrum, making diagnosis a challenge. The aim of this study was to review AFST cases and to report previously unknown histological features, which we confirmed by genetic analysis.We reviewed 276 cases diagnosed as solitary fibrous tumours/haemangiopericytomas (232 cases), unclassified tumours of fibroblastic differentiation (36 cases), and recently diagnosed AFSTs (eight cases), and retrieved 13 cases compatible with AFST. Immunohistochemical staining was performed for these cases, all 13 of which were analysed by reverse transcription polymerase chain reaction and fluorescence in-situ hybridization. The histological findings were as follows: amianthoid fibres, extravasation of red blood cells, haemosiderin deposition, aggregates of foamy histiocytes, cystic change, necrosis, and haemorrhage. Immunohistochemically, the tumour cells were positive for epithelial membrane antigen (four of 13 cases), desmin (six of 13 cases), CD163 (13 of 13 cases), CD68 (seven of 13 cases), oestrogen receptor (13 of 13 cases), progesterone receptor (three of 13 cases), and STAT6 (one of 13 cases, weak nuclear staining), but they were negative for CD34, -smooth muscle actin, muscle-specific actin, S100, pan-cytokeratin, MDM2, and CDK4. The AHRR-NCOA2 fusion gene was detected in eight cases, and NCOA2 gene rearrangement in nine cases.We revealed the previously unreported histological variation and immunohistochemical findings of AFST, and confirmed them by using genetic methods. The results suggested that AFST should be considered in the diagnosis of fibrous or fibrohistiocytic tumours with the above histological features.
Miyoshi T.,Okayama University of Science |
Doi M.,Sumitomo Besshi Hospital |
Hirohata S.,Okayama University of Science |
Sakane K.,Sumitomo Besshi Hospital |
And 6 more authors.
Journal of Atherosclerosis and Thrombosis | Year: 2010
Aim: The cardio-ankle vascular index (CAVI) has been proposed as a new noninvasive marker of arterial stiffness independent of blood pressure. We investigated the association of the CAVI with coronary atherosclerosis and left ventricular (LV) systolic and diastolic function in patients with ischemic heart disease (IHD). Methods: A total of 206 consecutive subjects undergoing coronary angiography were enrolled. CAVI measurement and echocardiography were performed simultaneously. Patients having significant coronary stenosis were classified into the IHD group. Results: CAVI in the IHD group (n 133) was significantly higher than in the non-IHD group (n 73) (9.1±1.3 vs. 8.7±1.2, p 0.02). In all IHD patients, CAVI was negatively correlated with LV ejection fraction (LVEF) (r=-0.31, p<0.01), LV mass index (r 0.24, p<0.01) and angiographic scores of coronary atherosclerosis. Stepwise regression analysis revealed that CAVI was independently associated with LVEF, along with a history of myocardial infarction, LV mass index, and left atrial diameter in all IHD patients (p<0.01). In the sub-analysis of IHD patients with preserved LVEF, CAVI was correlated with echocardiographic parameters regarding LV diastolic function. Multivariate analysis demonstrated that the increased CAVI was significantly associated with LV diastolic dysfunction in patients with preserved LVEF. Conclusion: CAVI, a new parameter of aortic stiffness, was independently associated with LV systolic and diastolic function as well as coronary artery disease in IHD patients.
Tsuge M.,Okayama University of Science |
Goto S.,Sumitomo Besshi Hospital |
Kato F.,Sumitomo Besshi Hospital |
Morishima T.,Okayama University of Science
Clinical Pediatrics | Year: 2010
From November to December in 2006, we experienced 4 pediatric cases with an elevation of the serum transaminase levels accompanied by acute gastroenteritis. All examined stool specimens were norovirus positive according to the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay. The clinical courses of these cases were the same as those of common gastroenteritis. Blood examinations showed only a slight elevation of the transaminase levels at the onset of gastroenteritis, while the symptoms were severe. Interestingly, the transaminase levels significantly increased after gastroenteritis disappeared. The average period between the onset of gastroenteritis and the peak of transaminase levels was 13.8 days. In all cases, the patients were treated with the administration of glycyrrhizin, and the transaminase levels returned to normal approximately 4 weeks (average 26.8 days) after the onset of gastroenteritis, thus suggesting that an elevation of the transaminase levels in association with norovirus gastroenteritis may therefore be a self-limited process which may demonstrate a relatively good natural prognosis. Norovirus is one of the important pathogens which cause an elevation in the serum transaminase levels in young children. When an elevation in the transaminase levels in association with gastroenteritis is observed in young children, it is important to continuously follow up such patients even after the gastroenteritis has disappeared and to perform a virus search based on examinations of stool specimens using an RT-PCR assay in order to detect the presence of norovirus infections. © 2010 The Author(s).
Fujii M.,Okayama Rosai Hospital |
Fujii M.,Okayama University of Science |
Fujimoto N.,Okayama Rosai Hospital |
Hiraki A.,Okayama University |
And 8 more authors.
Cancer Science | Year: 2012
Malignant pleural mesothelioma (MPM) usually develops pleural fluid. We investigated the value of DNA methylation in the pleural fluid for differentiating MPM from lung cancer (LC). Pleural fluid was collected from 39 patients with MPM, 46 with LC, 25 with benign asbestos pleurisy (BAP) and 30 with other causes. The methylation of O6-methylguanine-DNA methyltransferase (MGMT), p16INK4a, ras association domain family 1A (RASSF1A), death-associated protein kinase (DAPK), and retinoic acid receptor β (RARβ) was examined using quantitative real-time PCR. DNA methylation of RASSF1A, p16INK4a, RARβ, MGMT and DAPK was detected in 12 (30.8%), 3 (7.7%), 11 (28.2%), 0 (0.0%) and five patients (12.8%) with MPM, and in 22 (47.8%), 14 (30.4%), 24 (52.2%), 1 (2.2%) and six patients (13.0%) with LC, respectively. The mean methylation ratios of RASSF1A, p16INK4a and RARβ were 0.37 (range 0.0-2.84), 0.11 (0.0-2.67) and 0.44 (0.0-3.32) in MPM, and 0.87 (0.0-3.14), 1.16 (0.0-5.35) and 1.69 (0.0-6.49) in LC, respectively. The methylation ratios for the three genes were significantly higher in LC than in MPM (RASSF1A, P = 0.039; p16INK4a, P = 0.005; and RARβ, P = 0.002). Patients with methylation in at least one gene were 3.51 (95% confidence interval, 1.09-11.34) times more likely to have LC. Hypermethylation seemed no greater with MPM than with BAP. Extended exposure to asbestos (≥30 years) was correlated with an increased methylation frequency (P = 0.020). Hypermethylation of tumor suppressor genes in pleural fluid DNA has the potential to be a valuable marker for differentiating MPM from LC. © 2011 Japanese Cancer Association.
PubMed | Kagawa Prefectural Central Hospital, Okayama University of Science and Sumitomo Besshi Hospital
Type: Journal Article | Journal: Heart Asia | Year: 2016
Several lines of evidence suggest that atrial fibrillation (AF) may be a consequence of vascular disease. We investigated the relationship between cardio-ankle vascular index (CAVI), a new index of arterial stiffness, and the presence of paroxysmal AF (PAF).181 outpatients (91 patients with PAF and 90 age- and gender-matched subjects without PAF) were analysed for their sinus rhythm. The CAVI was significantly higher in patients with PAF than in subjects without PAF (9.01.0 vs 8.70.8, p<0.01). In all subjects, the CAVI was significantly correlated with the left ventricular mass index (r=0.30, p<0.01), left atrial diameter (r=0.22, p<0.01), and augmentation index, a parameter of wave reflection (r=0.32, p<0.01), in addition to age, systolic blood pressure and pulse pressure. Logistic analysis demonstrated that the CAVI was independently associated with PAF even after adjustment for confounding factors. The adjusted OR of PAF was 1.8 for each unit increase in the CAVI (p=0.01).Our finding suggests that increased arterial stiffness may be involved in the maintenance of AF.
Yoshioka H.,Kurashiki Central Hospital |
Hotta K.,Okayama University |
Kiura K.,Okayama University |
Takigawa N.,Okayama University |
And 9 more authors.
Journal of Thoracic Oncology | Year: 2010
BACKGROUNDS: Efficacy of gefitinib therapy strongly depends on epidermal growth factor receptor (EGFR)-mutation status in Asian patients with non-small cell lung cancer. Recently, the survival advantage of erlotinib, another tyrosine kinase inhibitor, was not affected by EGFR mutation status in a phase III trial, indicating that patients with EGFR-wild-type (EGFR-wt) tumors might also benefit from this tyrosine kinase inhibitor. The aim of this trial was to evaluate the efficacy and toxicity of erlotinib in Japanese patients with EGFR-wt tumors. METHODS: The primary end point was an objective response. Patients with EGFR-wt tumors previously receiving one to three chemotherapy regimens were enrolled in this trial. The mutation status was assessed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. Erlotinib was administered (150 mg/d) until disease progression or unacceptable toxicities occurred. RESULTS: Thirty patients were enrolled between January and December 2008. Objective response was observed in one patient (3.3%), and the disease became stable in 18 patients (60.0%). Skin rash was the most common side effect. Grades 3-4 adverse events included pulmonary embolism, keratitis, and anemia. Two other patients developed interstitial lung disease (grades 1 and 2). Nevertheless, all these events were reversible, resulting in no treatment-related deaths. With a median follow-up time of 10.7 months, the median survival time and median progression-free survival times were 9.2 and 2.1 months, respectively. CONCLUSION: This is the first prospective biomarker study showing that erlotinib therapy for pretreated patients with EGFR-wt tumors seems to have a modest activity with no irreversible toxicity. Copyright © 2009 by the International Association for the Study of Lung Cancer.
Phase II trial of gefitinib in combination with bevacizumab as first-line therapy for advanced non-small cell lung cancer with activating EGFR gene mutations: The okayama lung cancer study group trial 1001
Ichihara E.,Okayama University |
Ichihara E.,Vanderbilt University |
Hotta K.,Okayama University |
Nogami N.,Shikoku Cancer Center |
And 18 more authors.
Journal of Thoracic Oncology | Year: 2015
Purpose: Whether bevacizumab enhances the effect of the epidermal growth factor receptor (EGFR) inhibitor gefitinib on EGFR mutant non-small cell lung cancers (NSCLCs) remains unknown. We conducted a phase II trial to investigate the efficacy and safety of gefitinib when combined with bevacizumab as first-line therapy in patients with advanced NSCLC harboring EGFR gene mutations. Methods: In this trial, 42 patients with a performance status of 0 to 2 received gefitinib (250 mg/d) and bevacizumab (15 mg/kg, every 3 weeks). The primary end point of this study was the 1-year progression-free survival (PFS) rate. We assumed that a 1-year PFS rate of 55% would indicate potential usefulness and that a 1-year PFS rate of 40% would constitute the lower limit of interest. Results: Forty-two patients were enrolled in the study with a median age of 73 (range 42-86) years. Activating EGFR gene mutations included exon 19 deletion (57%) and L858R point mutations in exon 21 (38%). The objective response rate was 73.8% and included two complete responses. The 1-year PFS rate and median PFS time were 56.7% (95% confidence interval [CI] 39.9-70.5) and 14.4 months (95% CI 10.1-19.2), respectively. The median PFS differed significantly between EGFR exon 19 deletion and the L858R point mutation (18.0 versus 9.4 months, respectively; p = 0.006). The median overall survival had not yet been reached. Severe adverse events included grade 3 skin rash (15%), hypertension (17%), aspartate transaminase/alanine aminotransferase elevation (17%), proteinuria (7%), intracranial hemorrhage (2%), and grade 4 perforation of the digestive tract (2%). There were no treatment-related deaths. Conclusion: Gefitinib in combination with bevacizumab as first-line therapy seems to be a favorable and well-tolerated treatment for patients with advanced NSCLC with activating EGFR gene mutations, especially those with EGFR exon 19 deletion mutations, although the primary end point was not met because the lower limit of the CI was less than 40%. © 2014 by the International Association for the Study of Lung Cancer.
PubMed | Nagayama Eye Clinic, The University of Shimane, Sumitomo Besshi Hospital, Okayama University and 3 more.
Type: Clinical Trial | Journal: Advances in therapy | Year: 2016
We examined the sustainability of the intraocular pressure (IOP)-lowering efficacy of travoprost (0.004%) ophthalmic solution in subjects with normal tension glaucoma (NTG).Travoprost ophthalmic solution was given once daily at 9PM to subjects with newly diagnosed NTG or with NTG who had not received any ocular hypotensives within the previous 30days. IOP was measured at three time points (9AM, 1PM, and 5PM) at baseline and week12 visits, and at one time point (9AM) at week4 and week 8visits. Conjunctival hyperemia, superficial punctate keratopathy, and other adverse events were evaluated during the observation period.Thirty subjects (12males and 18females; mean age 65.6years) from 32 subjects enrolled were included in the efficacy analysis. The mean IOPs (standard deviation) of 16.61.4, 15.71.8, and 15.72.2mmHg at 9AM, 1PM, and 5PM, respectively, at baseline reduced significantly to the mean IOPs of 13.01.8, 12.71.8, and 12.81.6mmHg, respectively, at week12 (P<0.0001 for every time point). Together with the mean IOPs of 13.41.9mmHg at week4 and 13.21.9mmHg at week8, the pooled IOP during the observation period for up to 12weeks showed a statistically and clinically significant reduction of IOP at 9AM. (3.4mmHg or 20.3% reduction from baseline, P<0.0001). There were no adverse events leading to treatment discontinuation.This multi-center collaborative study suggests that IOP-lowering efficacy of travoprost ophthalmic solution persists during the day at the clinically relevant level in subjects with NTG.Alcon Japan Ltd.University Hospital Medical Information Network, UMIN ID: 000011621.
Miyoshi T.,Okayama University |
Doi M.,Sumitomo Besshi Hospital |
Hirohata S.,Okayama University |
Kamikawa S.,Okayama University |
And 6 more authors.
Heart and Vessels | Year: 2011
Adipocyte fatty acid binding protein (A-FABP) has been reported to be involved in insulin resistance, lipid metabolism, and atherosclerosis; however, little is known about the effect of medication on the change in circulating A-FABP in human subjects. We evaluated the effects of angiotensin II type 1 receptor blocker (ARB) on arterial stiffness and its association with serum A-FABP in patients with hypertension. Thirty patients newly diagnosed with essential hypertension were treated with olmesartan (20 mg/day), an ARB, for 6 months. Serum levels of A-FABP and high-sensitivity C-reactive protein (hsCRP) were examined and the cardio-ankle vascular index (CAVI), which is a marker of arterial stiffness, was also determined. Serum A-FABP at baseline was significantly correlated with the body mass index (r = 0.45, P = 0.01), homeostasis model assessment as a marker of insulin resistance (r = 0.53, p>0.01), and systolic blood pressure (r = 0.37, P = 0.047), and tended to be correlated with low-density lipoprotein cholesterol, triglyceride, and CAVI. Olmesartan treatment resulted in a significant decrease in CAVI, serum A-FABP levels, and hsCRP, besides a significant reduction of blood pressure. Multiple regression analysis revealed that the change in CAVI was independently correlated with the change in serum A-FABP. Olmesartan ameliorated arterial stiffness in patients with hypertension, which may be involved in the reduction of serum A-FABP. © 2010 Springer.
PubMed | Ehime University and Sumitomo Besshi Hospital
Type: | Journal: Clinical ophthalmology (Auckland, N.Z.) | Year: 2016
To examine the characteristics of visual field defects and optical coherence tomography (OCT) findings in eyes with intrachoroidal cavitation (ICC) and investigate the similarities between these results and glaucomatous changes.We retrospectively analyzed patients diagnosed with ICC based on peripapillary radial cross-sectional scans performed with OCT. Visual field was measured with the Humphrey automated visual field analyzer SITA standard central 24-2 program, and macular ganglion cell complex (GCC) thickness was measured in 99 mm areas on OCT. The positive rates for the Anderson criteria, site of visual field defect, and mean GCC thickness in each quadrant were compared; the association between these results and ICC location was assessed.Fifteen eyes from eleven patients (five males and six females; mean age, 54.610.7 years) were selected for investigation. ICC was detected in the inferior temporal side of the optic disc in all studied eyes. The positive rate for the Anderson criteria was 73.3% (11/15 eyes). Visual field defects were most commonly observed in the cluster that corresponded to the superior Bjerrum area (53.3%; 8/15 eyes). GCC thickness was significantly lower in the inferior side, where the ICC was located, than the superior side, where the ICC was absent (P=0.0001). GCC thinning that correlated with ICC was observed in 66.7% (10/15 eyes) of the ICC eyes.Visual field and GCC findings on OCT in ICC eyes are extremely similar to those observed in superior visual field defect-type early glaucoma, indicating a possible difficulty in distinguishing the two conditions.