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Akira Tsujimura,
Yoichi Yamamoto,
Saburo Sakoda,
Hidenobu Okuda,
Keisuke Yamamoto,
Shinichiro Fukuhara,
Iwao Yoshioka,
Hiroshi Kiuchi,
Tetsuya Takao,
Yasushi Miyagawa, Norio Nonomura
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ABSTRACT: OBJECTIVES: To assess which motor and non-motor symptoms are closely related to overactive bladder severity in male patients with Parkinson's disease. METHODS: A total of 160 male patients (mean age 71.4 ± 8.2 years) diagnosed with Parkinson's disease were included in the present study at Osaka University and affiliated hospitals. The severity of Parkinson's disease was classified as stage 3, 4 or 5 based on the Hoehn and Yahr staging system. Disease duration was 8.9 ± 5.1 years. Age, seven items from the Unified Parkinson's Disease Rating Scale motor section part III and three non-motor symptoms were assessed by multivariate analysis for their impact on the overactive bladder symptom score, a specific questionnaire for overactive bladder. RESULTS: Overactive bladder symptom score was significantly higher in the group with severe motor symptoms related to finger taps and gait than in the group with mild motor symptoms related to these two factors. Furthermore, overactive bladder symptom score of patients with erectile dysfunction and constipation was significantly higher than that in patients without these symptoms. Multivariate analysis identified only finger taps and constipation as factors independently associated with overactive bladder symptom score. CONCLUSIONS: Although a study on a larger scale is required to further assess the association of Parkinson's disease symptoms with overactive bladder symptom score, information on finger taps and severity of constipation should be obtained when assessing urological patients with Parkinson's disease.
International Journal of Urology 05/2013; · 1.75 Impact Factor
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ABSTRACT: OBJECTIVE: To elucidate the effects of nocturia, one of the most bothersome of symptoms, on health-related quality of life (QOL), we examined the correlation between nocturia-specific QOL and other lower urinary tract symptoms (LUTS). METHODS: Patients who visited our hospital complaining of LUTS were assessed retrospectively. A total of 259 men with LUTS answered the following questionnaires: International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), Nocturia QOL questionnaire (NQOL), and the Benign Prostatic Hyperplasia Impact Index (BII). The Spearman rank correlation coefficient was used to examine the correlation between NQOL total score and NQOL subdomain scores of sleep/energy and bother/concern and scores of other questionnaires. We then compared NQOL score in patients with or without OAB symptoms. RESULTS: The NQOL total score correlated significantly not only with IPSS total, IPSS storage symptoms, IPSS voiding symptoms, and QOL index but also with the OABSS and BII scores. The NQOL total score was significantly higher in the non-OAB vs OAB patients, indicating that OAB may deteriorate QOL as it relates to nocturia. In nocturia subgroups 0 to 2 (mild nocturia), NQOL score was significantly higher in non-OAB than in OAB patients, whereas in the nocturia subgroups 3 to 5 (severe nocturia), NQOL score was not significantly different between non-OAB and OAB patients. CONCLUSION: The NQOL total score correlated significantly with IPSS, OABSS, and BII scores. Symptoms of OAB and bother due to benign prostatic hyperplasia might affect QOL in patients with nocturia.
Urology 05/2013; · 2.43 Impact Factor
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ABSTRACT: High-dose-rate (HDR) brachytherapy as monotherapy is a comparatively new brachytherapy procedure for prostate cancer. In addition to the intrinsic advantages of brachytherapy, including radiation dose concentration to the tumor and rapid dose fall-off at the surrounding normal tissue, HDR brachytherapy can yield a more homogeneous and conformal dose distribution through image-based decisions for source dwell positions and by optimization of individual source dwell times. Indication can be extended even to T3a/b or a part of T4 tumors because the applicators can be positioned at the extracapsular lesion, into the seminal vesicles, and/or into the bladder, without any risk of source migration or dropping out. Unlike external beam radiotherapy, with HDR brachytherapy inter-/intra-fraction organ motion is not problematic. However, HDR monotherapy requires patients to stay in bed for 1-4 days during hospitalization, even though the actual overall treatment time is short. Recent findings that the α/β value for prostate cancer is less than that for the surrounding late-responding normal tissue has made hypofractionation attractive, and HDR monotherapy can maximize this advantage of hypofractionation. Research on HDR monotherapy is accelerating, with a growing number of publications reporting excellent preliminary clinical results due to the high 'biologically effective dose (BED)' of >200 Gy. Moreover, the findings obtained for HDR monotherapy as an early model of extreme hypofractionation tend to be applied to other radiotherapy techniques such as stereotactic radiotherapy. All these developments point to the emerging role of HDR brachytherapy as monotherapy for prostate cancer.
Journal of Radiation Research 03/2013; · 1.68 Impact Factor
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ABSTRACT: BACKGROUND: We retrospectively investigated the efficacy and safety profile of weekly low-dose docetaxel (DTX) with estramustine in comparison with triweekly standard-dose DTX treatment for Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: Between April 2002 and January 2011, 75 CRPC patients were treated with triweekly DTX (60-75 mg/m2 every 3 weeks) (standard-dose group), and 76 CRPC patients were treated with weekly low-dose DTX (20-30 mg/m2 on days 2 and 9 with estramustine 560 mg on days 1-3 and 8-10) every 3 weeks (low-dose group). Prostate-specific antigen (PSA) response and progression-free and overall survival were analyzed in each group. RESULTS: Median serum PSA level of the standard-dose group and low-dose group was 25.0 and 35.5 ng/ml, respectively. In the standard-dose and low-dose groups, 57.8 and 65.2 % of patients, respectively, achieved a PSA decline ≥50 %. There was no significant difference in either median time to progression between the standard-dose group (10.0 months) and low-dose group (7.1 months) or in median duration of survival between the standard-dose group (24.2 months) and low-dose group (30.6 months). Multivariate analysis with a Cox proportional hazards regression model showed that DTX treatment protocol did not influence the risk of death. Incidences of grade 3-4 neutropenia, febrile neutropenia, and thrombocytopenia were significantly higher in the standard-dose versus low-dose group (58.7 vs. 7.9 %, 16.0 vs. 3.9 %, and 8.0 vs. 0 %, respectively). CONCLUSION: For Japanese CRPC patients, weekly low-dose DTX combined with estramustine has similar efficacy to standard-dose DTX but with fewer adverse events.
International Journal of Clinical Oncology 03/2013; · 1.41 Impact Factor
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ABSTRACT: PURPOSE: We previously established a novel method of primary culture for human colorectal cancer. This method, termed the CTOS method, involves the preparation of multicellular spheroids of primary cancer cells that are cultured so that cell-cell contact is maintained. Here we applied the CTOS method to human urothelial cancer. MATERIALS AND METHODS: CTOSs were prepared from xenografts or primary human bladder urothelial cancer tumors following the same protocol used for human colorectal cancer. The CTOSs were characterized using immunohistochemistry, Western blot and PCR. RESULTS: We established a xenograft from a primary bladder urothelial cancer and isolated and cultured CTOSs from the xenograft tumor. The CTOSs retained the characteristics of the original tumor as well as those of the xenograft. HRG promoted the growth of the CTOSs. Both inhibitors of PI3K and mTOR inhibited HRG-induced CTOS growth. Lapatinib, but not erlotinib, inhibited HRG-induced CTOS growth. We also prepared CTOSs from primary tumors of bladder urothelial cancer. The success rate of establishing primary CTOSs from non-muscle-invasive urothelial cancer was 90.7% and that from muscle-invasive cancer was 68.2%. The overall success rate was 84.2%. HRG promoted the growth of primary CTOSs from 4 of 7 patients. CONCLUSIONS: Here we report a method for establishing primary cultures of human urothelial cancer cells. Stimulation of the growth by HRG in CTOSs from xenografts and primary tumors suggests the possibility of molecular targeting therapy against HER3 signaling for human urothelial cancer. The CTOS method might be useful for selecting patients for molecular targeting drugs like lapatinib.
The Journal of urology 01/2013; · 4.02 Impact Factor
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Jun-Ya Kaimori,
Satomi Iwai,
Masaki Hatanaka,
Takumi Teratani,
Yoshitsugu Obi,
Hidetoshi Tsuda,
Yoshitaka Isaka,
Takashi Yokawa,
Kagayaki Kuroda,
Naotsugu Ichimaru,
Masayoshi Okumi,
Koji Yazawa,
Hiromi Rakugi, Norio Nonomura,
Shiro Takahara,
Eiji Kobayashi
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ABSTRACT: The main objective of this study was to assess cardiac death (CD) kidney grafts before transplantation to determine whether blood oxygen level-dependent (BOLD) and diffusion MRI techniques can predict damage to these grafts after transplantation. We assessed CD kidney tissue by BOLD and diffusion MRI. We also examined pathological and gene expression changes in CD kidney grafts before and after transplantation. Although there was significantly more red cell congestion (RCC) in the inner stripe of the outer medulla (IS) in both 1 h after cardiac death (CD1h) and CD2h kidneys destined for grafts before transplantation compared with CD0h (p<0.05), CD2h, but not CD1h, kidney grafts had significantly different RCC in the IS 2 days after transplantation (p<0.05). Consistent with these pathological findings, tissue plasminogen activator (tPA) gene expression was increased only in the cortex and medulla of CD2h kidney grafts after transplantation. BOLD MRI successfully and non-invasively imaged and quantified RCC in the IS in both CD1h and CD2h kidney grafts (p<0.05). Diffusion MRI also non-invasively assessed increased the apparent diffusion coefficient in the IS and decreased it in the outer stripe (OS) of CD2h grafts, in concordance with interstitial edema in the IS and tubule cellular edema in the OS. These two types of edema in the outer medulla could explain the prolonged RCC in the IS only of CD2h kidney grafts, creating part of a vicious cycle inhibiting red cells coming out of capillary vessels in the IS. Perfusion with University of Wisconsin solution before MRI measurements did not diminish the difference in tissue damage between CD1h and CD2h kidney grafts. BOLD and diffusion MRI, which are readily available non-invasive tools for evaluating CD kidney grafts tissue damage, can predict prolonged organ damage, and therefore the outcome, of transplanted CD kidney grafts.
PLoS ONE 01/2013; 8(5):e63573. · 4.09 Impact Factor
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ABSTRACT: Testicular cancer is a rare disease that affects 1-2 in 100,000 people in Japan ; however, it is a very significant disease in that it has a high prevalence amongst young adults aged in their 20s and 30s and it brings about metastasis from a relatively early stage. The 2009 edition of the Testicular Cancer Clinical Practice Guidelines sets out a detailed summary of 32 clinical questions (CQ) considered necessary in routine clinical practice across the fields of epidemiology, diagnosis, treatment, etc, in the form of recommendations and commentary. These CQs are considered extremely important in understanding the foundation of future testicular cancer treatment guidelines. In this symposium, five doctors gave lectures consisting of the following contents in which they validated the guidelines and gave concrete clinical practice examples through cases they had experienced themselves with regards to the treatment strategies for (1) stage I patients, (2) patients with advanced cancer and (3) patients with extragonadal germ cell tumors. (1) Stage I patients : In seminoma cases, the doctors focused on the relapse prevention effect provided by single-agent carboplatin adjuvant chemotherapy. In non-seminoma cases, treatment options were considered according to risk based on the presence or absence of vascular invasion, a prognostic factor. (2) Patients with advanced cancer : 30% of testicular cancers are metastatic and progress to advanced cancer. In refractory cases resistant to bleomycin, etoposide and cisplatin therapy, etoposide ifosfamide, and cisplatin therapy and vinblastine, ifosfamide and cisplatin therapy have been used, but without satisfactory results and the development of new salvage chemotherapy is an important issue. The therapeutic strategies against advanced testicular cancer were narrowed down to (2) -1) therapeutic effects from ultra-high-dose chemotherapy, (2) -2) salvage chemotherapy in cases where residual tumors are observed in induction chemotherapy and (2) -3) minimally invasive surgical treatment for residual tumors after chemotherapy. Concrete clinical cases from basic treatment strategies to the latest findings in refractory cancer patients were presented and considered in detail. (3) Patients with extragonadal germ cell tumors : Extragonadal germ cell tumors account for less than 5% of all germ cell tumors, but they can be cured with multimodality therapy. Therefore, it is important to reach an accurate diagnosis and provide the correct treatment. This disease is suspected in patients with elevated α-fetoprotein and human chorionic gonadotropin without the appearance of tumors in the testes, and tumors can be observed on the center line of the body such as the mediastinum or retroperitoneum. Traditionally, computed tomography-guided biopsy has been carried out in diagnosis. However, new techniques such as endoscopic ultrasound-guided biopsy have also been reported in recent years and the latest information, including treatments, was presented at this symposium.
Hinyokika kiyo. Acta urologica Japonica 12/2012; 58(12):713-714.
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ABSTRACT: Most stage I testicular germ cell tumors are curable by orchiectomy alone. However, some tumors recur and require subsequent treatment. The point for the management of stage I testicular germ cell tumors is how to reduce the recurrence rate by appropriate adjuvant treatment with less adverse events. The strategy for stage I seminoma and stage I nonseminoma is different. The adjuvant treatment options include radiotherapy and 1-2 courses of carboplatin for seminoma and retroperitoneal lymph node dissection (RPLND) and 1-2 courses of bleomycin, etoposide and cisplatin chemotherapy for nonseminoma. This review discusses recent literature on adjuvant treatment and updates the consensus for the management of stage I testicular germ cell tumor.
Hinyokika kiyo. Acta urologica Japonica 12/2012; 58(12):715-720.
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ABSTRACT: BACKGROUND: Nonadherence to treatment regimens for immunosuppressive agents is one of the major risk factors for allograft failure in kidney transplant recipients. The aim of this study was to estimate the relative effect of daily dosing on treatment adherence, not to identify how patients are non-adherent, in long-term kidney transplant recipients. METHODS: In January 2009, a cross-sectional, anonymous, and voluntary questionnaire survey was given to kidney transplant recipients who regularly visited Inoue Hospital. A self-reporting questionnaire underestimates nonadherence, but we reasoned that the effect of the dosing regimen should be estimated with relative accuracy by using the generalized ordered logit/partial proportional hazard odds model given that the distribution patterns in the degree of nonadherence have been shown to be similar with other measures. RESULTS: Of 336 eligible patients, 312 (92.9 %) participated in this study. Two hundred seventy-four patients (87.8 %) were more than 3 years post-transplant. Univariate analysis revealed that a single daily dose was significantly associated with better adherence. After controlling for age, sex, time since transplantation, and the number of prescribed drugs, the effect of a single daily dose still remained significant [odds ratio, 0.40 (95 % confidence interval, 0.19-0.81); p = 0.011]. Several sensitivity analyses yielded similar results. CONCLUSIONS: To our knowledge, this is the first report that, in long-term kidney transplant recipients, a single daily regimen-one of few modifiable factors-might improve treatment adherence and allograft survival.
Clinical and Experimental Nephrology 10/2012; · 1.37 Impact Factor
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ABSTRACT: We aimed to analyse late toxicity associated with external beam radiation therapy (EBRT) for prostate cancer using uniform dose-fractionation and beam arrangement, with the focus on the effect of 3D (CT) simulation and portal field size. We collected data concerning patients with localized prostate adenocarcinoma who had been treated with EBRT at five institutions in Osaka, Japan, between 1998 and 2006. All had been treated with 70 Gy in 35 fractions, using the classical 4-field technique with gantry angles of 0°, 90°, 180° and 270°. Late toxicity was evaluated strictly in terms of the Common Terminology Criteria for Adverse Events Version 4.0. In total, 362 patients were analysed, with a median follow-up of 4.5 years (range 1.0-11.6). The 5-year overall and cause-specific survival rates were 93% and 96%, respectively. The mean ± SD portal field size in the right-left, superior-inferior, and anterior-posterior directions was, respectively, 10.8 ± 1.1, 10.2 ± 1.0 and 8.8 ± 0.9 cm for 2D simulation, and 8.4 ± 1.2, 8.2 ± 1.0 and 7.7 ± 1.0 cm for 3D simulation (P < 0.001). No Grade 4 or 5 late toxicity was observed. The actuarial 5-year Grade 2-3 genitourinary and gastrointestinal (GI) late toxicity rates were 6% and 14%, respectively, while the corresponding late rectal bleeding rate was 23% for 2D simulation and 7% for 3D simulation (P < 0.001). With a uniform setting of classical 4-field 70 Gy/35 fractions, the use of CT simulation and the resultant reduction in portal field size were significantly associated with reduced late GI toxicity, especially with less rectal bleeding.
Journal of Radiation Research 09/2012; · 1.68 Impact Factor
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ABSTRACT: We previously reported on the accumulation of a substantial amount of free N-acetylneuraminic acid (Neu5Ac)-containing complex-type N-glycans in human pancreatic cancer cells (Yabu M, Korekane H, Takahashi H, Ohigashi H, Ishikawa O, Miyamoto Y. 2012. Accumulation of free Neu5Ac-containing complex-type N-glycans in human pancreatic cancers. Glycoconjugate J Epub ahead of print). In the present paper, we further extend our cancer glycomic study of human prostate cancer. Specifically, we demonstrate that, in addition to the free Neu5Ac-containing N-glycans, significant amounts of free deaminoneuraminic acid (KDN)-containing N-glycans had accumulated in the prostate cancer tissues from four out of five patients. Indeed in one of the four cases, the free KDN-glycans accumulated as major components in prostate cancer tissue. The structures of the KDN-containing free oligosaccharides were analyzed by a variety of methods. Specifically we used fluorescent labeling with aminopyridine combined with two dimensional mapping, KDNase digestion and mass spectrometry to facilitate identification. The analysis also utilized newly synthesized KDN-linked oligosaccharides as standards. The prostate-specific glycans were composed of five species having the following sequence, KDN-Gal-GlcNAc-Man-Man-GlcNAc (α2,6-KDN-linked glycans being the dominant form). The most abundant free KDN-containing N-glycan was KDNα2-6Galβ1-4GlcNAcβ1-2Manα1-3Manβ1-4GlcNAc followed by KDNα2-6Galβ1-4GlcNAcβ1-2Manα1-6Manβ1-4GlcNAc. This is the first study to show unequivocal chemical evidence for the occurrence of KDN-glycoconjugates in human tissues together with their detailed structures. These oligosaccharides might be developed as tumor markers, especially for prostate cancer.
Glycobiology 09/2012; · 3.58 Impact Factor
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ABSTRACT: A 79-year-old man presented with a mass lesion under the left kidney that was revealed by abdominal ultrasonography. The retroperitoneal tumor was removed by transabdominal exploration. Histopathological diagnosis was a leiomyosarcoma. Seven years after the first operation, he presented with left flank pain. Computed tomography showed a mass lesion in the abdominal wall. Tumor resection was performed. The pathological diagnosis was recurrence of leiomyosarcoma. The patient remains free from disease recurrence 1 year after the second surgery.
Hinyokika kiyo. Acta urologica Japonica 09/2012; 58(9):487-90.
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Yoshitsugu Obi,
Naotsugu Ichimaru,
Takayuki Hamano,
Kodo Tomida,
Isao Matsui,
Naohiko Fujii,
Masayoshi Okumi,
Jun-Ya Kaimori,
Koji Yazawa,
Yukito Kokado,
Yoshiharu Tsubakihara, Norio Nonomura,
Hiromi Rakugi,
Shiro Takahara,
Yoshitaka Isaka
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ABSTRACT: Posttransplant malignancy (PTM) is a limiting factor both for patient and allograft survival in kidney transplant recipients (KTRs). We hypothesized that active vitamin D compounds (AVD) could reduce PTM development in KTRs. Ambulatory KTRs in a Japanese prospective cohort were followed from August 2007 to November 2010. The outcome of interest was newly diagnosed PTM. A propensity score (PS) of having received AVDs was estimated using 26 clinically relevant factors. We used the Cox proportional hazards model with stratification by PS tertiles on the assumption that baseline hazard functions differ among tertiles. As sensitivity analyses, we used inverse probability weighting and PS matching. Among 218 participants, the median age was 50 (interquartile range [IQR], 40 to 59) years, 63.3% were male, median time since transplantation was 11.2 (IQR, 5.2 to 17.1) years, and mean estimated GFR was 41.3 (SD, 15.6) mL/min per 1.73 m(2). At baseline, 42.2% had been treated with AVDs mainly for glucocorticoid-induced osteoporosis. AVDs used were calcitriol (58.7%) and alfacalcidol (41.3%). During follow-up, PTM developed in 5.4% of 92 AVD users and 8.7% of 126 nonusers. Poor vitamin D status was common in the participants, but the serum 25-hydroxyvitamin D level was not significantly associated with PTM in Cox regression analysis. After stratifying patients by PS tertiles, we found that AVDs were significantly associated with a lower risk of PTM (HR 0.25 [0.07 to 0.82]). Sensitivity analyses yielded similar results. AVDs are potential chemopreventive agents against PTM in KTRs. Cancer Prev Res; 5(10); 1229-35. ©2012 AACR.
Cancer Prevention Research 08/2012; 5(10):1229-35. · 4.91 Impact Factor
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Koichi Tsutahara,
Masayoshi Okumi,
Yoichi Kakuta,
Toyofumi Abe,
Koji Yazawa,
Shuji Miyagawa,
Katsuyoshi Matsunami,
Hideaki Otsuka,
Junya Kaimori,
Shiro Takahara, Norio Nonomura
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ABSTRACT: Background
Recent studies have identified T cells and natural killer T (NKT) cells as important mediators in renal ischemia-reperfusion (I/R) injury. The recruitment of these cells is induced by chemotaxis factors. We investigated the effects of blocking CXCR3 and CCR5 by an antagonist (TAK) using a rat renal I/R injury model.Methods
The Sprague-Dawley rats were either subjected to sham operation or left renal occlusion for 45 min followed by reperfusion and contralateral nephrectomy. The control or TAK groups were, respectively, injected phosphate-buffered saline or TAK at 30 min prior to clamp. Serum creatinine, tubular injury, chemokines expression and infiltrating cells were assessed.ResultsTAK treatment significantly suppressed the elevation in serum creatinine (sham 0.40 ± 0.05 mg/dL, control 2.86 ± 0.67 mg/dL, TAK 1.60 ± 0.73 mg/dL) and resulted in a lower tubular injury score compared with the control group (sham 0, control 4.8 ± 0.3, TAK 3.3 ± 1). The mRNA expression of chemokines that bind to CXCR3 and CCR5 in the post-ischemic kidneys was elevated at 1 h after reperfusion in each group. Moreover, the infiltration of CD4+ T cells and CD8+ NKT cells in the control group increased compared with the sham group and TAK injection significantly suppressed the number of CD4+ T cells (sham 13.5 ± 3.5 × 10(4) cells, control 28.9 ± 15.4 × 10(4) cells, TAK 11.8 ± 3.5 × 10(4) cells) and the number of CD8+ NKT cells (sham 11.7 ± 5.4 × 10(4) cells, control 30.1 ± 8.6 × 10(4) cells, TAK 11.8 ± 2.9 × 10(4) cells).Conclusions
These findings suggest that the blocking of CXCR3 and CCR5 suppress the infiltration of T cells and NKT cells and have a protective effect on kidneys that are injured by I/R.
Nephrology Dialysis Transplantation 08/2012; · 3.40 Impact Factor
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ABSTRACT: Objectives: Hyponatremia is reported to be associated with poor survival in localized renal cell carcinoma and metastatic renal cell carcinoma treated with immunotherapy. However, there are no reports on the relationship between hyponatremia and prognosis of metastatic renal cell carcinoma treated with molecular targeted therapy. We evaluated the prognostic significance of hyponatremia in metastatic renal cell carcinoma treated with molecular targeted therapy as first-line therapy. Methods: We retrospectively analyzed a database comprising 87 patients treated from April 2008 to July 2011 with sorafenib or sunitinib as first-line therapy for metastatic renal cell carcinoma. Patients were divided into three groups according to serum sodium level: severe hyponatremia (≤134 mEq/L), mild hyponatremia (135-137 mEq/L) and normal natremia (≥138 mEq/L). Results: Median cancer-specific survival time was 8.8 months in the patients with severe and mild hyponatremia, and 32.6 months in the patients with normal natremia (P < 0.001). Multivariate analysis showed severe and mild hyponatremia to be significantly associated with cancer-specific survival (hazard ratio 6.228; 95% confidence interval 2.161-17.947, P = 0.001; hazard ratio 3.374; 95% confidence interval 1.294-8.798, P = 0.013), respectively. Neutrophilia and high C-reactive protein level (C-reactive protein ≥1.0 mg/dL) were significant prognostic factors to predict inferior cancer-specific survival. In Harrell's concordance index calculation, hyponatremia could significantly improve the predictive accuracy for estimation of survival probability (P = 0.028). Conclusions: Hyponatremia (<138 mEq/L), neutrophilia and high C-reactive protein levels seem to represent significant predictive factors for cancer-specific survival in metastatic renal cell carcinoma patients treated with molecular targeted therapy as first line therapy. Furthermore, hyponatremia might be significantly associated with chronic inflammation and tumor aggressiveness.
International Journal of Urology 08/2012; · 1.75 Impact Factor
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ABSTRACT: Fibroblast growth factor 23 (FGF23), rather than parathyroid hormone (PTH), has been shown to be the major factor behind hypophosphatemia in the early period after renal transplantation. However, it is not clear whether phosphate wasting persists in the chronic phase. Purpose of our study is to elucidate whether FGF23 can also explain phosphate wasting, if any, in the chronic phase.
In this cross-sectional observational study, we enrolled 247 recipients who had received a graft more than 1 year prior to this study. We compared the phosphate metabolism of recipients and predialysis chronic kidney disease (CKD) patients who are matched on age and estimated glomerular filtration rate (eGFR). We also investigated the determinants of tubular reabsorption of phosphate normalized for glomerular filtration rate (TmP/GFR), as an index of renal threshold for phosphate.
Recipients had a median dialysis vintage of 27.0 months and eGFR 41.2 mL/min/1.73 m(2). Whereas hypophosphatemia (<2.4 mg/dL) was observed in 6.1% of the recipients, 55.2% had TmP/GFR lower than 2.4 mg/dL. Recipients showed significantly lower TmP/GFR in all CKD stages than their predialysis counterparts, indicating that phosphate wasting persists in the chronic phase. Compared to predialysis patients, the recipients in stages 2T and 3T showed lower phosphate and higher intact PTH levels, despite a higher percentage being active vitamin D users. However, in stage 4T, phosphate retention masked relative hypophosphatemia. FGF23 was higher in the recipients across all CKD stages, but adjustment for vitamin D prescription revealed that transplantation had no effect on FGF23. Multiple regression analysis in the recipients showed significant negative associations of intact PTH and dialysis vintage with TmP/GFR.
Renal phosphate wasting persists in the chronic-phase renal transplantation recipients even with normophosphatemia. Persistent hyperparathyroidism and longer dialysis vintage, not FGF23, was associated with renal phosphate wasting in the chronic phase. Such an impact on phosphate metabolism of the factors determined in dialysis period could be called as "uremic memory". This novel finding in the chronic phase is in sharp contrast to the previous finding in the early phase that FGF23 levels are determinants of phosphate wasting.
Bone 07/2012; 51(4):729-36. · 4.02 Impact Factor
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Atsunari Kawashima,
Hitoshi Takayama,
Norihiko Kawamura,
Noriteru Doi,
Mototaka Sato,
Koji Hatano,
Akira Nagahara,
Motohide Uemura,
Yasutomo Nakai,
Kensaku Nishimura,
Susumu Miyoshi,
Kiyoshi Kawano,
Kazuo Nishimura, Norio Nonomura,
Akira Tsujimura
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ABSTRACT: Neoadjuvant chemotherapy (NC) for bladder cancer has been reported to significantly improve the 5-year survival rate. The aim of the present study was to examine the roles of ERCC1 and Snail in determining the response to chemotherapy in bladder cancer treated with NC and radical cystectomy (RC). The expression of the Snail and ERCC1 proteins was determined by immunohistochemical staining of specimens obtained from 58 patients with bladder tumors treated with NC and RC. The correlation between clinical response and the expression of Snail and ERCC1 was investigated. Snail and ERCC1 were co-expressed in 24 (41.4%) of the 58 patients. A marked correlation was found between the expression of Snail and ERCC1 (P=0.001). The co-expression of Snail and ERCC1 was not able to predict pathological complete response (P=0.202). Results of the univariate analysis revealed that the co-expression of Snail and ERCC1 predicted shorter disease-free survival (DFS) and overall survival (OS) than the negative expression of Snail and/or ERCC1. Moreover, the co-expression of ERCC1 and Snail was the only predictive factor for both DFS (P=0.029) and OS (P=0.040). The expression of Snail was correlated with that of ERCC1 and the co-expression of Snail and ERCC1 was the only significant predictive factor of shorter DFS and OS in patients with bladder cancer treated with NC and RC.
Oncology letters 07/2012; 4(1):15-21. · 0.11 Impact Factor
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ABSTRACT: BACKGROUND: Hormone ablation therapy is the standard therapy for prostate cancer; however, there are large individual differences in the duration of response to the therapy. We investigated, in this retrospective multicenter study, the association between genetic polymorphic variations in steroidogenesis-related genes and the risk of progression to castration-resistant prostate cancer (CRPC) in Japanese patients after androgen deprivation therapy. METHODS: Two hundred and fourteen Japanese patients with prostate cancer who were receiving androgen deprivation therapy were enrolled in this study. We investigated 22 single-nucleotide polymorphisms (SNPs) from 8 genes related to steroidogenesis. The SNPs were assayed by polymerase chain reaction (PCR)-based methods. The different genotypes in this cohort were analyzed according to a case-control status of progression to CRPC at the median duration of hormonal therapy. A logistic regression method with adjustments for patients' characteristics was applied for the analysis.After applying the logistic regression method, we performed Cox regression analysis, following Kaplan-Meier and log-rank analyses. RESULTS: In the logistic regression analysis four genetic polymorphisms, rs743572, rs6162, rs6163, and rs1004467, in the CYP17A1 gene were significantly associated with a risk of progression to CRPC (p < 0.05). Cox regression analysis for these SNPs showed an association of risk of progression to CRPC with the rs743572 genotype (p = 0.02, odds ratio [OR] 0.43, 95 % confidence interval [CI] 0.22-0.85). CONCLUSION: The genetic backgrounds for CYP17A1 genes could influence the progression of prostate cancer to CRPC after androgen deprivation therapy.
International Journal of Clinical Oncology 06/2012; · 1.41 Impact Factor
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Koji Hatano,
Kazuo Nishimura,
Yasutomo Nakai,
Takahiro Yoshida,
Mototaka Sato,
Atsunari Kawashima,
Masatoshi Mukai,
Akira Nagahara,
Motohide Uemura,
Daizo Oka,
Masashi Nakayama,
Hitoshi Takayama,
Kiyonori Shimizu,
Norio Meguro,
Tsuyoshi Tanigawa,
Seiji Yamaguchi,
Akira Tsujimura, Norio Nonomura
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ABSTRACT: BACKGROUND: A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC). METHODS: Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m(2) on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days. RESULTS: The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1-93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia. CONCLUSIONS: The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity.
International Journal of Clinical Oncology 06/2012; · 1.41 Impact Factor
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Ryoichi Imamura,
Yoshitaka Isaka,
Ruben M Sandoval,
Naotsugu Ichimaru,
Toyofumi Abe,
Masayoshi Okumi,
Koji Yazawa,
Harumi Kitamura,
Jyunya Kaimori, Norio Nonomura,
Hiromi Rakugi,
Bruce A Molitoris,
Shiro Takahara
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ABSTRACT: BACKGROUND: The tissue-protective effects of erythropoietin (EPO) have been extensively investigated, and EPO administration can raise the hemoglobin (Hb) concentration. Recently, we reported that carbamylated erythropoietin (CEPO) protected kidneys from ischemia-reperfusion injury as well as EPO. METHODS: To investigate the clinical applications of CEPO, we next evaluated the long-term therapeutic effect of CEPO using a tubulointerstitial model rat. We randomized remnant kidney model rats to receive saline, EPO, or CEPO for 8 weeks. RESULTS: CEPO- and EPO-treated rats had improved serum creatinine levels compared with saline-treated remnant kidney model rats, although the Hb level was significantly increased in EPO-treated rats. Two-photon microscopy revealed that EPO/CEPO significantly ameliorated tubular epithelial cell damage assessed by endocytosis. In addition, CEPO or EPO protected endothelial cells with a sustained blood flow rate. EPO or CEPO suppressed the number of TUNEL-positive apoptotic cells with weak αSMA staining. Furthermore, PCR analysis demonstrated that TGF-β and type I collagen expression was attenuated in EPO- or CEPO-treated rats, accompanied by a significant decrease in interstitial fibrosis. CONCLUSION: We established a long-term therapeutic approach to protect tubulointerstitial injury with CEPO, and thus, the therapeutic value of this approach warrants further attention and preclinical studies.
Clinical and Experimental Nephrology 06/2012; · 1.37 Impact Factor
