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PubMed | Red Cross, Takikawa Municipal Hospital, Nippon Telegraph and Telephone, University of Toyama and 8 more.
Type: Journal Article | Journal: Anticancer research | Year: 2016

To determine prognostic factors for overall survival (OS) in renal cell carcinoma (RCC) patients with bone metastasis in the targeted-therapy era.We conducted a retrospective multi-institutional review of the medical records of 149 RCC patients with bone metastasis. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify independent factors associated with OS.The median OS was 13.4 months. In multivariate analysis, molecular-targeted therapy, nephrectomy and surgery for bone metastasis were independent prognostic factors. Bone-modifying agents (BMAs) were not associated with OS. The median OS of patients receiving molecular-targeted therapy after diagnosis of bone metastasis was significantly better than that of those who did not receive targeted therapy.Molecular-targeted therapy, nephrectomy and surgery for bone metastasis should be considered for RCC patients with metastasis in the bones.


PubMed | Sunagawa City Medical Center, Nippon Telegraph and Telephone, Nihon University and Hokkaido University
Type: Journal Article | Journal: The British journal of radiology | Year: 2016

Accurate evaluation of joint space width (JSW) is important in the assessment of rheumatoid arthritis (RA). In clinical radiography of bilateral hands, the oblique incidence of X-rays is unavoidable, which may cause perceptional or measurement error of JSW. The objective of this study was to examine whether tomosynthesis, a recently developed modality, can facilitate a more accurate evaluation of JSW than radiography under the condition of oblique incidence of X-rays.We investigated quantitative errors derived from the oblique incidence of X-rays by imaging phantoms simulating various finger joint spaces using radiographs and tomosynthesis images. We then compared the qualitative results of the modified total Sharp score of a total of 320 joints from 20 patients with RA between these modalities.A quantitative error was prominent when the location of the phantom was shifted along the JSW direction. Modified total Sharp scores of tomosynthesis images were significantly higher than those of radiography, that is to say JSW was regarded as narrower in tomosynthesis than in radiography when finger joints were located where the oblique incidence of X-rays is expected in the JSW direction.Tomosynthesis can facilitate accurate evaluation of JSW in finger joints of patients with RA, even with oblique incidence of X-rays.Accurate evaluation of JSW is necessary for the management of patients with RA. Through phantom and clinical studies, we demonstrate that tomosynthesis may achieve more accurate evaluation of JSW.


PubMed | Red Cross, National Hospital Organization Hokkaido Cancer Center, Fukushima Medical University, Obihiro Kosei Hospital and 10 more.
Type: | Journal: Oncotarget | Year: 2017

The limited number of available treatments for patients with small-cell lung cancer (SCLC) has prompted us to further investigate the biology of SCLC by molecular profiling. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC, who had undergone surgery at 16 institutions between January 2003 and January 2013, and analyzed the association between disease-specific survival and protein expression of c-kit, c-Met, epidermal growth factor receptor, human EGFR-related 2, vascular endothelial growth factor receptor II, anaplastic lymphoma kinase, mediator complex subunit 12 (MED12), and transforming growth factor beta receptor II (TGF-RII) by immunohistochemistry (IHC). Of the 125 evaluable samples, all tumors expressed MED12, and 123 samples (98.4%) expressed TGF-RII. MED12 was highly expressed in the nucleus in 92% of the positive samples while TGF-RII was highly expressed in the cytoplasm in 55% of the positive samples. High c-kit expression was an independent favorable prognostic marker confirmed by multivariate analysis (hazard ratio: 0.543, 95% confidence interval: 0.310-0.953, p = 0.033). Both the relapse free-survival and overall survival of patients who underwent adjuvant chemotherapy were statistically longer in those with high c-kit expression (n = 38) than those with intermediate, low, or no c-kit expression (n = 19) (not reached vs 11.6 months, p = 0.021; not reached vs 25.9 months, p = 0.028). IHC for c-kit may offer a prognostic marker for early-stage SCLC, and the results for MED12 and TGF-RII may suggest the biological characteristics of SCLC. Further investigation of the roles of their related molecules in early stage SCLC is required.


Fukumori D.,Sunagawa City Medical Center | Matsuhisa T.,Sunagawa City Medical Center | Taguchi K.,Sunagawa City Medical Center | Minato M.,Sunagawa City Medical Center
Hepato-Gastroenterology | Year: 2011

It is very rare for ectopic pancreas to become cancerous. We herein report on a case of ectopic pancreatic cancer developed in the stomach. A neoplastic lesion was detected in the pyloric part in an upper GIS of a 76-year-old female, requiring biopsy, but because it was classified as Group I, it was observed temporarily. Following blood collection after ∼2 years, the CA19-9 increased from 177.5 to 279.5, so a GIS was again performed. Although the pyloric part of the stomach became more stenosed than before, it was still considered Group I disease based on biopsy findings. When EUS was performed, the tumor appeared as a submucosal tumor, and was thus suspected as GIST. In an abdominal CT, a neoplastic lesion with a clear boundary was observed in the pylorus, as was an enlarged lymph node in the hepatoduodenal ligament. Therefore malignancy could not be ruled out, and a gastrectomy on the pylorus side, lymph node dissection (D2), and cholecystectomy were performed. The tumor was a submucosal tumor covered by a coherent mucosa. According to histopathological findings, it was diagnosed as ectopic pancreatic cancer developed in the ectopic pancreas (Heinrich type II), consisting of acinar tissue and capillary tubes. Thus ectopic pancreas should be considered in the differential diagnosis of gastric submucosal tumors. Regarding surgery for ectopic pancreas, it is considered necessary to establish a treatment policy by making an immediate pathological diagnosis with sufficient consideration of the possibility of malignancy. © H.G.E. Update Medical Publishing S.A.


Kobayashi S.,Sapporo Medical University | Tateno M.,Sapporo Medical University | Park T.W.,Sapporo Medical University | Utsumi K.,Sunagawa City Medical Center | And 4 more authors.
PLoS ONE | Year: 2011

Background: The apolipoprotein E (APOE) ε4 allele has been reported to be a risk factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Previous neuropathological studies have demonstrated similar frequencies of the APOE ε4 allele in AD and DLB. However, the few ante-mortem studies on APOE allele frequencies in DLB have shown lower frequencies than post-mortem studies. One reason for this may be inaccuracy of diagnosis. We examined APOE genotypes in subjects with AD, DLB, and a control group using the latest diagnostic criteria and MRI, SPECT, and MIBG myocardial scintigraphy. Methods: The subjects of this study consisted of 145 patients with probable AD, 50 subjects with probable DLB, and a control group. AD subjects were divided into two groups based on age of onset: early onset AD (EOAD) and late onset AD (LOAD). All subjects had characteristic features on MRI, SPECT, and/or myocardial scintigraphy. Results: The rate of APOE4 carrier status was 18.3% and the frequency of the ε4 allele was 9.7% in controls. The rate of APOE4 carrier status and the frequency of the ε4 allele were 47% and 27% for LOAD, 50% and 31% for EOAD, and 42% and 31% for DLB, respectively. Conclusion: The APOE4 genotypes in this study are consistent with previous neuropathological studies suggesting accurate diagnosis of AD and DLB. APOE4 genotypes were similar in AD and DLB, giving further evidence that the ε4 allele is a risk factor for both disorders. © 2011 Kobayashi et al.


Hasegawa T.,Sapporo Medical University | Asanuma H.,Sapporo Medical University | Ogino J.,Sapporo Medical University | Hirohashi Y.,Sapporo Medical University | And 4 more authors.
Human Pathology | Year: 2013

Previously, we showed that the expression of potassium channel tetramerization domain-containing 12 (KCTD12), which was discovered by a proteomics approach, is associated with high-risk behavior of gastrointestinal stromal tumors (GISTs). Here, we examined the distribution and expression of this protein by immunostaining with a commercially available polyclonal KCTD12 antibody in GISTs (n = 64) and other types of malignancy (n = 168) to clarify its diagnostic and clinical significance. Diffuse KCTD12 immunoreactivity was found in most GISTs (52 cases; 81%). KCTD12 expression was observed primarily in vascular endothelial cells, Purkinje cells of the cerebellum, and some neurons scattered throughout the cerebral cortex. KCTD12 was absent from not only the interstitial cells of Cajal but also interstitial cells of Cajal hyperplasia that was encountered incidentally in colon diverticulitis. KCTD12 immunostaining was also seen in malignant peripheral nerve sheath tumors (2/10 cases; 20%), synovial sarcomas (2/10; 20%), solitary fibrous tumor (1/8; 13%), angiosarcoma (1/7; 14%), and colon adenocarcinoma (1/24; 4%). In survival analyses, the 5-year recurrence-free survival rate of patients without KCTD12 expression was only 16.7% compared with 95.6% in those with KCTD12 expression (P <.0001). Ki-67 and KCTD12 were significant predictors of recurrence-free survival, and KCTD12 expression provided additional information about recurrence-free survival after accounting for Ki-67 status. Overall, KCTD12 expression was specific for GISTs from neoplastic and nonneoplastic adult tissues other than brain and served as a predictor of GIST recurrence. These findings suggest that KCTD12 is a useful and reliable biomarker for both the diagnosis and prognosis of GIST. © 2013 Elsevier Inc.


We report a case of a 71-year-old woman who had extensive cerebral infarction associated with acute type A aortic dissection. We urgently performed ascending aortic graft replacement. Postoperative computed tomography of the brain taken immediately after the aortic surgery showed further aggravation of the right cerebral edema and a midline shift. The patient underwent emergent internal and external decompression of the brain. Eventually, consciousness recovered to normal level though preoperative left paraplegia persisted. She was discharged 150 days after the operation. We conclude that immediate internal and external cerebral decompression after surgery for acute type A dissection with preoperative cerebral malperfusion can prevent postoperative higher brain dysfunction.


Sohma H.,Sapporo Medical University | Imai S.-I.,Sapporo Medical University | Takei N.,Sapporo Medical University | Honda H.,Mikuri Immunology Laboratory Inc. | And 6 more authors.
Frontiers in Aging Neuroscience | Year: 2013

Background: Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid beta peptide (Aβ42). Using a cell culture model we previously identified annexin A5, a Ca2+, and phospholipid binding protein, as an AD biomarker. Plasma level of annexin A5 was significantly higher in AD patients compared to that in a control group. On the other hand, AD has been identified to share a number of clinical and pathological features with Dementia with Lewy bodies (DLB). The present study was done to examine whether or not plasma annexin A5 is a specific marker for AD, when being compared with the levels of DLB patients. As Apolipoprotein E (ApoE) gene subtype ε4 (ApoE-ε4) has been noticed as the probable genetic factor for AD, we also examined and compared ApoE genotype in both AD and DLB. Methods: Blood samples were obtained from 150 patients with AD (aged 77.6 ± 6.5 years), 50 patients of DLB (79.4 ± 5.0) and 279 community-dwelling healthy elderly individuals of comparable age and sex (75.6 ± 8.1). All AD patients met NINCDS-ADRDA criteria and all DLB patients were diagnosed as probable DLB according to the latest consensus diagnostic criteria. Quantification was done using the Chemiluminescent Enzyme Immunoassay (CLEIA) Technique (SphereLight assay) using the monoclonal antibodies against annexin A5. DNA genotyping of ApoE was performed by distinguishing unique combinations of Hha1 fragments of PCR-amplified genomic DNA products. Results: The plasma level of annexin A5 was significantly higher in AD patients than in the healthy individuals (control) (P < 0.0001). The plasma annexin A5 level was also significantly higher in DLB patients than in the control group (P < 0.0001). From the ROC curves with plasma annexin A5 concentrations, the mean areas under the curve were 0.863 and 0.838 for the AD/control and DLB/control, respectively. The rate of ApoE4 carrier status and the frequency of the ε4 allele were significantly higher in AD or DLB than in control and there was no significant difference between AD and DLB. Conclusions: These results suggest that both annexin A5 and ApoE4 are common markers for AD and DLB. © 2013 Sohma, Imai, Takei, Honda, Matsumoto, Utsumi, Matsuki, Hashimoto, Saito and Kokai.


PubMed | Sunagawa City Medical Center and Sapporo Medical University
Type: | Journal: Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society | Year: 2017

Current diagnostic criteria recommend neuroimaging as a diagnostic support tool for the clinical diagnosis of dementia with Lewy bodies (DLB). Because DLB causes characteristic impairments and disabilities, such as neuroleptic hypersensitivity, which may significantly increase morbidity and mortality, its prompt and correct diagnosis is very important. The aim of this study was to evaluate the extent to which diagnostic accuracy can be increased by using different combinations of brain perfusion single-photon emission computed tomography (bp-SPECT), Thirty-four patients with probable DLB (75.08.3years old; 14 men, 20 women) underwent bp-SPECT, MIBG scintigraphy, and DAT-SPECT.Our comparison of three functional imaging techniques indicated that MIBG scintigraphy (79%) and Dopamine-transporter (DAT) SPECT (79%) had better sensitivity for characteristic abnormalities in DLB than bp-SPECT (53%). The combination of the three modalities could increase sensitivity for diagnosis of DLB to 100%. Additionally, the ratio of patients with rapid eye movement sleep behaviour disorder was significantly higher in the positive finding group on MIBG scintigraphy than in the negative finding group.In terms of stand-alone diagnostic means, priority should be placed on MIBG scintigraphy or DAT-SPECT for the diagnosis of DLB. However, our results suggest that the combination of bp-SPECT, MIBG scintigraphy, and DAT-SPECT increased the accuracy of the clinical diagnosis of DLB.


PubMed | Sunagawa City Medical Center, Sapporo Shirakabadai Hospital and Sapporo Medical University
Type: Journal Article | Journal: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology | Year: 2016

The aim of this study was to evaluate post-tetanic potentiation of muscle twitch in myasthenia gravis (MG).Post-tetanic potentiation was evaluated by recording the compound muscle action potential (CMAP) of abductor pollicis brevis and movement-related potential (MRP) of the thumb using an accelerometer after tetanic stimulation of the median nerve at the wrist. After baseline recording, tetanic stimulation was delivered to the median nerve at a frequency of 10 Hz for 10s. The CMAP and MRP were successively recorded at baseline and at 5, 10, 30, 60, 90 and 120 s after tetanic stimulation. The chronological changes of CMAPs and MRPs were recorded bilaterally in 11 patients with MG, 9 patients with myopathies (disease controls), and 25 healthy control subjects.Maximal acceleration of MRP was significantly elevated during 10s after tetanic stimulation without any CMAP changes in all groups. However, statistical analysis detected a significant decrease in post-tetanic potentiation of maximal acceleration of MRP in MG patients only compared to healthy controls, but not in myopathy patients, which may imply impairment of excitation-contraction coupling in MG.Post-tetanic potentiation of muscle twitch is significantly diminished in MG, suggesting impaired excitation-contraction coupling.Measurement of post-tetanic potentiation using an accelerometer is a simple and sensitive method to detect impairment of excitation-contraction coupling in MG.

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