Masato Fujisawa

Kobe University, Kōbe, Hyōgo, Japan

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Publications (586)1565.43 Total impact

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    ABSTRACT: Rotavirus infections are a major cause of diarrhea in children in both developed and developing countries. Rotavirus genetics, patient immunity, and environmental factors are thought to be related to the severity of acute diarrhea due to rotavirus in infants and young children. The objective of this study was to provide a correlation between rotavirus genotypes, clinical factors and degree of severity of acute diarrhea in children under 5 years old in Surabaya, Indonesia. A cross-sectional study was conducted in children aged 1-60 months with acute diarrhea hospitalized in Soetomo Hospital, Surabaya, Indonesia from April to December 2013. Rotavirus in stool specimens was identified by ELISA and genotyping (G-type and P-type) using multiplex reverse transcription PCR. Severity was measured using the Ruuska and Vesikari scoring system. The clinical factors were investigated included patient's age (months), hydration, antibiotic administration, nutritional state, co-bacterial infection and co-viral infection. A total of 88 children met the criteria; 80.7% were aged 6-24 months, watery diarrhea was the most common type (77.3%) and 73.6% of the subjects were co-infected with bacteria, of which pathogenic Escherichia coli was the most common (42.5%). The predominant VP7 genotyping (G-type) was G2 (31.8%) and that of VP4 genotyping (P-type) was P[4] (31.8%). The predominant rotavirus genotype was G2P[4] (19.3%); G1P[4] and G9P[4] were uncommon with a prevalence of 4.5%. There were significant differences between the common genotype and uncommon genotype with respect to the total severity score of diarrhea (p <0.05). G3, G4 and G9 were significantly correlated with severe diarrhea (p = 0.009) in multivariate analyses and with frequency of diarrhea (>10 times a day) (p = 0.045) in univariate analyses, but there was no significant correlation between P typing and severity of diarrhea. For combination genotyping of G and P, G2P[4] was significantly correlated with severe diarrhea in multivariate analyses (p = 0.029). There is a correlation between rotavirus genotype and severity of acute diarrhea in children. Genotype G2P[4] has the highest prevalence. G3, G4, G9 and G2P[4] combination genotype were found to be associated with severe diarrhea.
    Gut Pathogens 12/2015; 7(1). DOI:10.1186/s13099-015-0048-2 · 2.28 Impact Factor
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    ABSTRACT: Prognostic significance of early tumor shrinkage following treatment with tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) has not been fully elucidated. The aim of this study was to assess the impact of early tumor shrinkage induced by first-line TKIs on overall survival (OS) in mRCC patients. This study retrospectively included 185 consecutive Japanese patients with mRCC treated with either sunitinib or sorafenib for at least 3 months as first-line molecular-targeted therapy between April 2011 and December 2014 at Kobe University Hospital and its affiliated institutions. Median OS in the 185 patients was 33.6 months. At 12 weeks after the introduction of TKIs, 9 patients had achieved tumor shrinkage from -100 to -50 %, 43 from -49 to -25 %, 61 from -24 to 0 %, and the remaining 72 patients showed an increase in tumor size. The median OS stratified according to tumor shrinkage as shown above was 59.2, 39.1, 31.4, and 16.1 months, respectively. Univariate analysis identified prior nephrectomy, Memorial Sloan Kettering Cancer Center (MSKCC) risk classification, C-reactive protein (CRP) level, liver metastasis, number of metastatic organs, histological subtype, sarcomatoid feature, and early tumor shrinkage as significant predictors of OS. Of these significant factors, only the MSKCC classification, CRP level, liver metastasis, and early tumor shrinkage were shown to be independently associated with OS on multivariate analysis. Early tumor shrinkage could be a useful predictor of OS in mRCC patients receiving TKIs as a first-line molecular-targeted agent.
    Targeted Oncology 09/2015; DOI:10.1007/s11523-015-0385-6 · 4.00 Impact Factor
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    ABSTRACT: According to the classical ladder theory, the mesonephric arteries (MAs) have a segmental arrangement and persist after regression of the mesonephros, with some of these vessels becoming definitive renal arteries. To avoid interruption of blood flow, such a vascular switching would require an intermediate stage in which two or more segmental MAs are connected to a definitive renal artery. To examine developmental changes, especially changes in the segmental distribution of MAs, we studied serial paraffin sections of 26 human embryos (approximately 5-7 weeks). At 5-6 weeks, 1-2 pairs of MAs ran anterolaterally or laterally within each of the lower thoracic vertebral segments, while 2-5 pairs of MAs were present in each of the lumbar vertebral segments, but they were usually asymmetrical. The initial metanephros, extending along the aorta from the first lumbar to first sacral vertebra, had no arterial supply despite the presence of multiple MAs running immediately anterior to it. Depending on increased sizes of the adrenal and metanephros, the MAs were reduced in number and restricted in levels from the twelfth thoracic to the second lumbar vertebra. The elimination of MAs first became evident at a level of the major, inferior parts of the metanephros. Therefore, a hypothetical arterial ladder was lost before development of glomeruli in the metanephros. At 7 weeks, after complete elimination of MAs, a pair of symmetrical renal arteries appeared near the superior end of the metanephros. In conclusion, the MAs appear not to persist to become a definitive renal artery. Copyright © 2015 Elsevier GmbH. All rights reserved.
    Annals of anatomy = Anatomischer Anzeiger: official organ of the Anatomische Gesellschaft 08/2015; 202:8-17. DOI:10.1016/j.aanat.2015.07.005 · 1.48 Impact Factor
  • Masatomo Nishikawa · Hideaki Miyake · Liu Bing · Masato Fujisawa
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    ABSTRACT: To analyze basal expression levels of multiple components in the autophagy pathway in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (mRCC) treated with mammalian target of rapamycin (mTOR) inhibitors, to identify factors predicting susceptibility to these agents. This study included 48 consecutive patients undergoing radical nephrectomy, who were diagnosed with mRCC and subsequently treated with either everolimus or temsirolimus. Expression levels of 5 major molecular markers involved in the signaling pathway associated with autophagy, including autophagy-related protein (Atg)5, Atg9, Beclin1, microtubule-associated protein light chain 3, and UNC-51-like kinase 1 (ULK1), were measured by immunohistochemical staining of primary renal cell carcinoma specimens. During the observation period of this study (median = 16.2mo), 36 patients developed disease progression, with a median progression-free survival (PFS) period of 7.6 months. Of several factors examined, bone metastasis, liver metastasis, and ULK1 expression were shown to have significant effects on the response to mTOR inhibitors. PFS was significantly correlated with the expression level of ULK1 in addition to bone and liver metastases on univariate analysis. Of these significant factors, ULK1 expression and liver metastasis were independently associated with PFS on multivariate analysis. It may be useful to consider expression levels of potential molecular markers in the autophagy pathway, particularly ULK1, in addition to conventional parameters, when selecting patients with mRCC who are likely to benefit from treatment with mTOR inhibitors. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urologic Oncology 08/2015; DOI:10.1016/j.urolonc.2015.07.013 · 2.77 Impact Factor
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    ABSTRACT: To improve understanding of the variations of bladder neck musculature, we investigated histological changes of the bladder neck associated with prostatic hyperplasia in adult male cadavers. We examined histological sections from 24 donated male cadavers with a mean age of 74 years. The sections were subjected to Azan staining and to immunohistochemical staining using desmin and S-100 antibodies. The collagen content per cross-sectional area was calculated and statistically compared. Existence of three muscle layers (submucosal longitudinal muscles, circular bladder neck muscles, and external longitudinal muscles) was confirmed at both the anterior and posterior regions of the bladder neck. An increase of prostate volume was significantly correlated with an increase of collagen fibers and thinning of muscle bundles in the anterior bladder neck. Both an increase of prostate volume and increasing age were significantly correlated with degeneration of the posterior bladder neck muscles. As prostatic hyperplasia advanced, the bladder neck muscles were progressively affected by fibrosis, with the circular muscle fibers becoming thin and fragmented. In addition, the severity of fibrosis associated with prostatic hyperplasia showed interindividual variation. We also devised a schematic classification of bladder neck morphology in adult men. Degeneration of muscle bundles in the bladder neck of adult males with prostatic hyperplasia was confirmed, and it was found that the bundles became thinner along with an increase of collagenous tissue. Our schematic classification of bladder neck morphology in adult men may be useful for further investigations. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    The Journal of urology 08/2015; DOI:10.1016/j.juro.2015.07.102 · 4.47 Impact Factor
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    ABSTRACT: To characterize the changes in seminogram findings in infertile men after varicocelectomy. This study included 71 consecutive infertile men who underwent microsurgical low ligation varicocelectomy and received 3 semen analyses, 1 before microsurgical varicocelectomy and again at 3 and 12 months after. Total motile sperm count (TMSC) was calculated using the following formula: [volume (mL) × concentration (millions/mL) × motility (%)]. Despite the lack of significant changes in the proportion of sperm with abnormal morphology, sperm concentration, motility, and TMSC in the 71 patients were significantly higher at 3 and 12 months after varicocelectomy than before surgery. However, no further improvement in these parameters at 12 months after varicocelectomy was noted compared with those at 3 months. Furthermore, when the included men were divided into 3 groups according to preoperative TMSC as <3 million, 3-9 million, and >9 million, TMSCs at 3 months after varicocelectomy in all 3 groups were significantly higher than those before varicocelectomy; however, TMSCs at 12 months after surgery in all groups were similar to those at 3 months. The level of improvement in semen parameters at 3 months after varicocelectomy may be stable at 12 months after surgery, irrespective of baseline values of TMSC. Therefore, varicocelectomy could be offered as a therapeutic option for infertile men, even for couples with an older woman, because its efficacy is evaluable at 3 months after surgery, and assisted reproductive technology could be immediately applied to ineffective cases. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urology 07/2015; 86(1). DOI:10.1016/j.urology.2015.04.014 · 2.19 Impact Factor
  • Journal of chemotherapy (Florence, Italy) 07/2015; DOI:10.1179/1973947815Y.0000000059 · 1.60 Impact Factor
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    ABSTRACT: A kidney transplant case with de novo donor-specific antibody showed monoclonal plasma cell infiltration into the graft with ABO incompatibility. Three years after transplantation, the patient's graft function suddenly deteriorated. Interstitial edema and the predominant infiltration of inflammatory plasma cells with kappa chain monoclonality were observed in biopsy specimens. The in situ hybridization of Epstein-Barr virus was negative and post-transplant lymphoproliferative disorder was not evident from radiological examinations. On laboratory examination, the patient had de novo donor-specific antibody for HLA-DQ. We suspected plasma cell-rich acute rejection for which methylprednisolone pulse therapy, plasma exchange, rituximab, and 15-deoxyspergualin were given. In the ensuing biopsy, the degree of plasma cell infiltration was similar to the first biopsy; however, kappa chain monoclonality relatively weakened. Owing to resistance to these treatments, intravenous immunoglobulin (IVIG) (0.5 g/kg/day) was added. The serum creatinine level gradually declined to 3.1 mg/dL; however, it increased up to 3.6 mg/dL again. In the final biopsy, the infiltrated plasma cells disappeared but severe interstitial fibrosis developed. This case showed difficulty in the diagnosis and treatment of plasma cell-rich acute rejection. A detailed consideration of this case may be helpful in understanding the clinical features and pathogenesis of this condition. © 2015 Asian Pacific Society of Nephrology.
    Nephrology 07/2015; 20 Suppl 2(S2):66-9. DOI:10.1111/nep.12471 · 2.08 Impact Factor
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    ABSTRACT: Background: The objective of this study was to retrospectively review oncological outcomes in patients with stage I testicular germ cell tumor (GCT). Patients and Methods: This study included 265 consecutive Japanese men undergoing orchiectomy for stage I testicular GCT, and a retrospective review of their records was performed. Results: Of these 265 patients, 192 and 73 were pathologically classified with seminoma and nonseminoma, respectively. Prophylactic radiation and chemotherapy were performed in 62 patients with seminoma and 6 with nonseminoma, respectively. Disease recurrence occurred in 12 seminoma patients, of whom 11 had not received prophylactic radiation therapy; however, all 12 achieved a complete response to bleomycin, etoposide and cisplatin therapy. Of the nonseminoma patients, 19 experienced disease recurrence and were then treated with bleomycin, etoposide and cisplatin followed additionally by the surgical resection of residual tumors and salvage chemotherapy in 7 and 4, respectively. There was no cancer-specific death in the 265 patients, and 5-year recurrence-free survival rates in patients with seminoma and nonseminoma were 92.6 and 72.8%, respectively. Furthermore, following factors appeared to be significantly associated with recurrence-free survival in these patients: age, T classification, microvascular invasion and adjuvant therapy for those with seminoma, and microvascular invasion for those with nonseminoma. Conclusions: Despite a generally favorable prognosis in Japanese men with stage I testicular GCT, intensive follow-up or prophylactic therapy should be considered for men with possible risk factors of disease recurrence.
    Current Urology 07/2015; 8(2):84-90. DOI:10.1159/000365695
  • Hiromoto Tei · Hideaki Miyake · Ken-ichi Harada · Masato Fujisawa
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    ABSTRACT: Background: To analyze the diagnostic performance of 12-core biopsy in detecting significant prostate cancer (PCa). Patients and Methods: This study included 206 PCa patients who underwent transrectal 12-core biopsy followed by radical prostatectomy. Radical prostatectomy specimens were anatomically divided into 12 areas according to the sampling cores, and the existence of significant cancer, defined by a tumor volume > 0.5 ml, was investigated. The detection rate of significant cancer in each area was calculated as follows: the number of positive core biopsies/the number of areas containing significant cancer × 100. Results: The overall detection rate of significant cancer in all areas was 53.6%. The detection rate was significantly higher in the standard sextant cores than in the additional 6 cores in patients with prostate-specific antigen ≥ 10 ng/ml, clinical stage ≥ T2, or biopsy Gleason score ≥ 7, but not in those with prostate-specific antigen Conclusions: Approximately half of the significant cancers were not accurately detected, and the detection rates in biopsy cores other than the sextant cores appeared to be significantly lower in PCa patients with aggressive features.
    Current Urology 07/2015; 8(2):91-95. DOI:10.1159/000365696
  • Masatomo Nishikawa · Hideaki Miyake · Masato Fujisawa
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    ABSTRACT: To analyze the clinical outcomes of the irinotecan plus nedaplatin (IN) regimen in patients with advanced germ cell tumors (GCTs) refractory to cisplatin-based combination chemotherapies. This study included a total of 20 consecutive advanced GCT patients who were categorized into intermediate- or poor-risk GCT groups according to the International Germ Cell Consensus Classification, and were judged to show refractory or relapsed disease after bleomycin, etoposide and cisplatin and cisplatin, ifosfamide and paclitaxel therapies. All 20 patients subsequently received IN therapy (irinotecan 100 mg/m(2) on days 1 and 15; nedaplatin 100 mg/m(2) on day 1) every 4 weeks. Following a median of 3 cycles of IN, 9 patients (45 %) achieved normalization of serum tumor markers. In addition, surgical resection of the residual tumors following IN was performed in 5 patients, of whom 4 were pathologically diagnosed with no viable cancer cells. At a median follow-up of 9 months, 11 patients (55 %) were alive, including 7 (35 %) with no evidence of disease, whereas the remaining 9 (45 %) died of disease progression. The median duration of overall survival after the introduction of IN to these 20 patients was 13.4 months. Severe hematological toxicities were observed in all patients, but were manageable. Although fatal treatment-related interstitial pneumonia occurred in 1 patient, other non-hematological toxicities were generally tolerable. Considering the markedly unfavorable characteristics of the included patients with advanced GCT who were intensively treated with cisplatin-based combination chemotherapies, IN could be regarded as having promising therapeutic activity with an acceptable toxicity profile.
    International Journal of Clinical Oncology 06/2015; DOI:10.1007/s10147-015-0861-0 · 2.13 Impact Factor
  • S Naito · H Sakai · K Hashine · T Tomita · N Shinohara · M Fujisawa · M Eto · S Ozono · H Akaza
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    ABSTRACT: The potential of S-1 for the treatment of metastatic renal cell carcinoma (mRCC) has been shown in two phase 2 studies. We aimed to assess the safety, tolerance, pharmacokinetics and clinical activity of S-1 combined with sorafenib in patients with mRCC. In this multicenter, single-arm, open-label, phase 1/2 study of S-1 plus sorafenib, we recruited patients with clear-cell or papillary renal cell carcinoma who had received a maximum of one prior cytokine-based regimen. The phase 1 primary endpoints were the maximum tolerated dose (MTD) and recommended dose (RD). S-1 was administered orally at 60, 80, 100 or 120 mg/day on days 1 to 28 of a 42-day cycle in combination with sorafenib (400 or 800 mg/day), given daily with dose adjustment. In phase 2, the primary endpoint was to assess the overall response rate (ORR) at the RD. Nine patients were enrolled into phase 1 and 21 (including 6 patients who received the RD in the phase 1 portion) were enrolled into phase 2. In the phase 1 portion, the MTD could not be determined, and the RD was defined as S-1 80 mg/m(2)/day on days 1-28+sorafenib 800 mg/day on days 1-42. In the phase 2 portion, 21 patients were fully assessable for efficacy and safety. The confirmed ORR was 52% (95% CI, 29.8-74.3), including one complete response (5%) and 10 partial responses (48%). The median progression free survival was 9.9 (95% CI, 6.5-17.1) months. The most frequently reported treatment-related adverse event for all grades was hand-foot skin reaction (100%). The major reasons for dose reduction were hand-foot skin reaction (38%) and rash (14%). Combination therapy with S-1 plus sorafenib is effective and tolerable for patients with mRCC. However, skin events management is important in S-1 plus sorafenib combination therapy. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:
    Annals of Oncology 06/2015; 26(9). DOI:10.1093/annonc/mdv280 · 7.04 Impact Factor
  • Noritoshi Enatsu · Hideaki Miyake · Koji Chiba · Masato Fujisawa
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    ABSTRACT: Purpose To evaluate retrospectively the outcomes of microdissection testicular sperm extraction (micro-TESE) in men with nonobstructive azoospermia (NOA) and to identify the parameters predicting successful sperm retrieval in this cohort of patients. Methods After excluding patients with normal testicular volume and serum follicle-stimulating hormone (FSH) level who received conventional TESE, this study included 329 consecutive NOA patients undergoing micro-TESE at our institution. The significance of several factors, including age, testicular volume, etiology and serum levels of FSH, luteinizing hormone (LH) and serum testosterone (T), as predictors of successful sperm retrieval, was evaluated. Results Of the 329 men included in this series, 246 (74.8 %), 40 (12.2 %), and 43 (13.1 %) were pathologically diagnosed with Sertoli cell only, maturation arrest, and hypospermatogenesis, respectively. Spermatozoa were retrieved in 97 (29.5 %) of these 329 men by micro-TESE. Older age and non-idiopathic etiology were significantly associated with the probability of successful sperm retrieval; however, there were no significant effects of testicular volume as well as serum levels of FSH, LH, and T on sperm retrieval outcome. Furthermore, Johnsen score of the micro-TESE specimen showed a significant association with whether spermatozoa were successfully retrieved. Univariate analysis of preoperative parameters identified older age and non-idiopathic etiology as significant predictors of successful sperm retrieval, of which only etiology appeared to be independently related to successful sperm retrieval on multivariate analysis. Conclusions Spermatozoa are significantly less likely to be successfully retrieved by micro-TESE in men with idiopathic azoospermia.
    Reproductive Medicine and Biology 06/2015; DOI:10.1007/s12522-015-0212-x
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    ABSTRACT: To investigate antimicrobial susceptibility patterns of various bacterial pathogens isolated from complicated urinary tract infection (UTI) cases, the Japanese Society of Chemotherapy, the Japanese Association of Infectious Disease, and the Japanese Society of Clinical Microbiology conducted the second nationwide surveillance from January to September 2011. With the cooperation of 42 medical institutions throughout Japan, 1036 strains belonging to 8 clinically relevant bacterial species were collected. Among methicillin-resistant Staphylococcus aureus (MRSA) strain, the vancomycin (VCM) MIC for 5.5% (3/55) of the strains was 2 μg/mL. Ampicillin, VCM, and linezolid were relatively active against 209 Enterococcus faecalis strains. The proportion of fluoroquinolone (FQ)-resistant strains was >20%. The MIC90 of FQs against the 382 Escherichia coli strains was 2-64 mg/L and the proportion resistant to FQs was approximately 30%. However, susceptibility of E. coli to sitafloxacin was still high (MIC90 = 2 mg/L). Fifty-eight (15.2%) of 382 E. coli, 6 (4.5%) of 132 Klebsiella pneumoniae, 1 (2.4%) of 41 Klebsiella oxytoca and 4 (6.8%) of 59 Proteus mirabilis strains were suspected of producing extended-spectrum beta-lactamase. Of 93 Pseudomonas aeruginosa strains, the proportions resistant to imipenem, amikacin, and ciprofloxacin were 21.5%, 4.3%, and 20.4%, respectively. Four strains (4.3%) were found to be multidrug-resistant. In complicated UTI cases, all of MRSA and E. faecalis were susceptible to all anti-MRSA agents. Sitafloxacin was active against other FQ-resistant E. coli strains. The isolation of extended-spectrum beta-lactamase-producing and multidrug-resistant strains increased. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Infection and Chemotherapy 06/2015; 21(9). DOI:10.1016/j.jiac.2015.05.014 · 1.49 Impact Factor
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    ABSTRACT: The purpose of this study is to identify significant immune-system related for symptom of patients with prostatic inflammation in order to investigate the etiology of prostatic inflammation which may relate to potentially chronic prostatitis (CP). We investigated the expression of immune system-related biomarkers such as Interleukin (IL) -6 (humoral immunity), CD-3 (T-lymphocyte), and CD-163 (macrophage) in prostate biopsy (PBx) specimens from patients with prostatic inflammation (without cancer) which had been neither clinically diagnosed benign prostatic hyperplasia nor chronic prostatitis. We examined the correlation between these markers' expressions and the symptom scores using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS)/quality of life (QOL) which are the index for lower urinary tract symptoms (LUTS). Our results showed CD-163 (macrophage) reflected pain or discomfort on NIH-CPSI scores (P = 0.0389 and r = 0.3307) in the patients with prostatic inflammation; however, the control patients had no significant correlation between symptom scores and those immune-related markers' expression. These results suggest that pain or discomfort related to macrophages in the relationship between immune-system and the symptom of prostatic inflammation. In conclusion, CD-163, related to immune-system (macrophage), correlated with symptoms (pain or discomfort) of prostatic inflammation and might represent a significant immune-system related biomarker for pain or LUTS score in potentially CP.
    International journal of clinical and experimental pathology 06/2015; 8(3):2408-14. · 1.89 Impact Factor
  • Akira Miyazaki · Hideaki Miyake · Ken-Ichi Harada · Masato Fujisawa
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    ABSTRACT: To identify patients with metastatic renal cell carcinoma (mRCC) who received tyrosine kinase inhibitors (TKIs) in both first- and second-line settings in order to investigate the association of oncological outcomes between the two lines of therapy. Patients with Methods: The study included 76 consecutive patients with mRCC treated with second-line TKI therapy after the failure of first-line TKI therapy. The association of oncological outcomes between first- and second-line therapies was analyzed in these 76 patients. In this series, the objective response rates (ORRs) to first- and second-line TKI therapies were 10.5% and 25.0%, respectively. The ORR to second-line TKI therapy was not significantly different among patients achieving a complete or partial response, stable disease and progressive disease to first-line TKI therapy (37.5%, 21.6% and 29.4%, respectively; p=0.34). The median durations of progression-free survival (PFS) with first- and second-line TKI therapies were 7.9 and 8.1 months, respectively, and there was no significant correlation between them (p=0.78). Out of the examined factors, the pre-treatment C-reactive protein level, number of metastatic sites and Memorial Sloan-Kettering Cancer Center risk classification model, but not the response to first-line TKI therapy, were independently associated with PFS on second-line TKI therapy, based on multivariate analysis. The clinical response to second-line TKI therapy is not dependent on that to first-line TKI therapy in patients with mRCC; therefore, it may not be necessary to switch to an alternative agent with a mechanism different from TKIs as second-line therapy, even if patients do not respond to first-line TKI therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 05/2015; 35(5):3067-73. DOI:10.1016/j.clgc.2015.08.002 · 1.83 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the oncological efficacy of tyrosine kinase inhibitors (TKIs) as first-line molecular-targeted therapy for Japanese patients with metastatic renal cell carcinoma (mRCC) in a routine clinical setting. This study included a total of 271 consecutive Japanese patients with TKI-naive mRCC, including 172 patients who received sorafenib and 99 who received sunitinib for ≥2 months as a first-line molecular-targeted agent. The prognostic outcomes of these patients were retrospectively assessed. During the observation period (median, 19 months), 126 patients (46.5%) succumbed to the disease and the median overall survival (OS) for the entire cohort was 33.1 months. The univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, histological subtype and sarcomatoid characteristics as significant predictors of OS. Of these factors, only the MSKCC classification, CRP level and liver metastasis were found to be independently associated with OS in the multivariate analysis. Furthermore, there were significant differences in OS according to the positivity for these 3 independent risk factors (i.e., negative for all factors vs. positive for a single factor vs. positive for 2 or 3 factors). These findings suggest that the introduction of TKIs as first-line molecular-targeted agents resulted in favorable cancer control outcomes in Japanese mRCC patients and that the prognosis of these patients may be stratified by 3 potential parameters, including the MSKCC classification, CRP level and liver metastasis.
    Molecular and Clinical Oncology 05/2015; 3(3):601-606. DOI:10.3892/mco.2015.487
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    ABSTRACT: Objectives To assess the significance of performance status as a prognostic factor after radical cystectomy for urothelial carcinoma of the bladder.Methods The present study included 730 consecutive patients with urothelial carcinoma of the bladder who underwent radical cystectomy. Clinicopathological outcomes in these patients were analyzed focusing on the impact of performance status, which was assessed using the Karnofsky Performance Status scale before surgery. Patients were classified into groups with Karnofsky Performance Status ≥90 and ≤80.ResultsA total of 561 (76.8%) and 169 (23.2%) patients were judged to have Karnofsky Performance Status ≥90 and ≤80, respectively. During a mean of 52.0 months, disease recurrence and mortality occurred in 257 (35.2%) and 249 (34.1%) patients, respectively, and the 5-year recurrence-free and overall survival rates were 64.1 and 65.3%, respectively. There were significant differences in age, hemoglobin, albumin, estimated glomerular filtration rate, pathological T stage and nodal involvement between the Karnofsky Performance Status ≥90 and ≤80 groups. Multivariate analysis showed independent impacts of Karnofsky Performance Status, pathological T stage, nodal involvement and lymphovascular invasion on recurrence-free survival, as well as independent impacts of Karnofsky Performance Status, age, body mass index, hemoglobin, pathological T stage, nodal involvement and lymphovascular invasion on overall survival.Conclusions The results suggest a significant association between impaired performance status and unfavorable prognosis in patients with urothelial carcinoma of the bladder undergoing radical cystectomy.
    International Journal of Urology 05/2015; 22(8). DOI:10.1111/iju.12804 · 2.41 Impact Factor
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    ABSTRACT: To investigate the optimal dose of vancomycin (VCM) for methicillin-resistant Staphylococcus aureus infections in the urological patients including renal dysfunction. We had 143 sets of available data from the consecutive patients treated in the urological department for analysis in VCM dose, VCM trough and estimated glomerular filtration rate: eGFR at VCM trough examination. Patients were classified according to eGFR level, and we calculated the regression line between VCM dose and VCM trough accordingly. Median VCM dose were 1000 (range 500-3500) mg per day, the VCM trough was 15.6 ± 7.89 μg/ml, and eGFR was 61.1 ± 27.2 ml/min/1.73 m(2). Our regression analysis (x axis: VCM dose (mg) and y axis: VCM trough (μg/ml) was statistically significant in the group with eGFR of 30-60 ml/min/1.73 m(2) (y = 26.103x + 481.7; r (2) = 0.1291) and the group with eGFR of 60-90 ml/min/1.73 m(2) (y = 48.891x + 350.75; r (2) = 0.2561) in both with (p = 0.021 and 0.035, respectively) or without (p = 0.012 and 0.004, respectively) adjustments by body weight for VCM doses. These data showed that the optimal dose of VCM varied according to the eGFR value in consecutive urological patients with various renal functions.
    International Urology and Nephrology 04/2015; 47(6). DOI:10.1007/s11255-015-0973-5 · 1.52 Impact Factor
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    ABSTRACT: To evaluate the expression of multiple molecular markers involved in autophagy, a cellular degradation pathway for the clearance of damaged or superfluous proteins and organelles, in localized prostate cancer (PC) to clarify the prognostic significance of these markers in patients undergoing radical prostatectomy (RP). Expression levels of 5 autophagy markers, including autophagy-related gene 5, autophagy-related gene 9, Beclin1, microtubule-associated protein light chain 3, and UNC-51-like kinase 1 (ULK1), in RP specimens from 160 consecutive patients with clinically localized PC were measured by immunohistochemical staining. Of these 5 markers, ULK1 expression was significantly correlated with the incidence of biochemical recurrence (BR). On univariate analysis, ULK1 expression, serum prostate-specific antigen level, pathologic stage, Gleason score, seminal vesicle invasion, and surgical margin status were identified as significant predictors of BR. All these significant factors except for seminal vesicle invasion were independently associated with BR on multivariate analysis. Furthermore, significant differences in BR-free survival according to the positive numbers of these 5 independent risk factors were noted, that is, BR occurred in 2 of 33 patients negative for risk factors (6.1%), 20 of 76 patients positive for 1 or 2 risk factors (26.3%), and 38 of 51 patients positive for ≥3 risk factors (74.5%). Collectively, these findings suggest that measurement of expression levels of potential autophagy markers, particularly ULK1, in RP specimens, in addition to conventional parameters, may contribute to the accurate prediction of BR after RP for localized PC. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urology 04/2015; 85(6). DOI:10.1016/j.urology.2015.03.006 · 2.19 Impact Factor

Publication Stats

4k Citations
1,565.43 Total Impact Points


  • 1997–2015
    • Kobe University
      • Division of Urology
      Kōbe, Hyōgo, Japan
  • 2014
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 2011
    • Institute for Molecular Medicine and Cell Therapy
      Düsseldorf, North Rhine-Westphalia, Germany
    • Government of the People's Republic of China
      Peping, Beijing, China
  • 2010
    • Hyogo Cancer Center
      Akasi, Hyōgo, Japan
  • 2009
    • Hyogo College of Medicine
      • Institute for Advanced Medical Sciences
      Nishinomiya, Hyōgo, Japan
  • 2008
    • Osaka City University
      • Department of Urology
      Ōsaka, Ōsaka, Japan
  • 2006
    • Vancouver General Hospital
      Vancouver, British Columbia, Canada
    • Nishiwaki Municipal Hospital
      Нишиваки, Hyōgo, Japan
  • 2003–2005
    • Kawasaki Medical University
      • Department of Urology
      Kurasiki, Okayama, Japan
    • Yokohama Ekisaikai Hospital
      Yokohama, Kanagawa, Japan