Publications by authors named "Kenjiro Kohri"

327 Publications

Bisphosphonate Use May Reduce the Risk of Urolithiasis in Astronauts on Long-Term Spaceflights.

JBMR Plus 2022 Jan 22;6(1):e10550. Epub 2021 Sep 22.

NASA Johnson Space Center Houston TX USA.

Long-duration spaceflight is associated with an increased risk of urolithiasis, and the pain caused by urinary calculi could result in loss of human performance and mission objectives. The present study investigated the risk of urolithiasis in astronauts during 6 months on the International Space Station, and evaluated whether the suppression of bone resorption by the bisphosphonate, alendronate (ALN), can reduce the risk. A total of 17 astronauts were included into the analysis: exercise using the advanced resistive exercise device (ARED) plus weekly oral 70 mg alendronate (ARED+ALN group,  = 7) was compared to resistive exercise alone (ARED group,  = 10). Urine volume decreased in both groups during spaceflight but recovered after return. The ARED group showed increased urinary calcium excretion from the 15th to 30th day of spaceflight, whereas urinary calcium was slightly decreased in the ARED+ALN group. Urinary N-terminal telopeptide (NTX) and helical peptide (HP) of type I collagen, as bone resorption markers, were elevated in the ARED group during and until 0 days after spaceflight, while there was no elevation in these parameters in the ARED+ALN group. Urinary oxalate and uric acid excretion tended to be higher in the ARED group than in the ARED+ALN group during spaceflight. These results demonstrate that astronauts on long-duration spaceflights may be at high risk for the formation of urinary calcium oxalate and calcium phosphate stones through increased urinary excretion of oxalate and uric acid, from degraded type I collagen, as well as of calcium from enhanced bone resorption. Our findings suggest that increased bone resorption during spaceflight, as a risk factor for urinary calculus formation, could be effectively prevented by an inhibitor of bone resorption. © 2021 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770998PMC
January 2022

A Proteomic Network Approach across the Kidney Stone Disease Reveals Endoplasmic Reticulum Stress and Crystal-Cell Interaction in the Kidney.

Oxid Med Cell Longev 2019 27;2019:9307256. Epub 2019 Oct 27.

Key Laboratory of Renal Calcification Disease Prevention and Treatment, Shenyang Medical College, 146 Huanghe North Street, Shenyang 110034, China.

Crystal-cell interactions are a vital step toward kidney stone formation. However, its mechanisms remained unclear. Here, a protein-protein interaction (PPI) network analysis of a kidney stone revealed that the proteins were enriched in a posttranslational protein modification process in the endoplasmic reticulum (ER). The study showed that the markers of ER stress, including Bip and CHOP, were upregulated, PERK and ATF6 were activated, and XBP-1 mRNA was spliced. An ER stress-specific protein, caspase-12, was activated in the apoptotic cells induced by calcium oxalate monohydrate (COM) crystals. The treatment with tunicamycin, an ER stress inducer, promoted the crystal-cell adhesion assayed by atomic absorption, reduced cell viability assayed by MTT, and downregulated the expression of proteins involved in the crystal formations. The treatment with salubrinal, an ER stress inhibitor, reversed the above effects for both tunicamycin and COM crystals. The aforementioned main observations were supported by study. These data demonstrated that ER stress was an essentially biological process of crystal-cell interactions. Our findings suggest that blocking ER stress may become a potential approach to preventing a kidney stone.
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http://dx.doi.org/10.1155/2019/9307256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854948PMC
April 2020

Active Phagocytosis and Diachronic Processing of Calcium Oxalate Monohydrate Crystals in an in vitro Macrophage Model.

Kidney Blood Press Res 2019 11;44(5):1014-1025. Epub 2019 Sep 11.

Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Background: We previously discovered that renal macrophages (Mφs) phagocytose renal calcium oxalate monohydrate (COM) crystals. This study investigated the processing of engulfed crystals using in vitro models.

Methods: J774.1 mouse Mφs were exposed to COM crystals and observed for 24 h using polarized light microscopy with/without cytochalasin B (CB), an inhibitor of phagocytosis, to confirm active crystal phagocytosis. LysoTracker and immunohistochemical staining using transmission electron microscopy for lysosomal-associated membrane protein 1 were used to confirm engulfed COM crystal uptake into lysosomes. Diachronic tracking of specific Mφs was performed to capture the entire course of engulfed COM crystal processing using polarized light microscopy. Follow-up studies of fluorescent COM (f-COM) crystals using imaging cytometry were performed in the presence and absence of nigericin to dissipate the pH gradient in acidic organelles.

Results: Phagocytosis rates increased with COM density and were significantly lower in cells treated with CB (p < 0.01). We observed that engulfed crystals colocalized within lysosomes of the Mφs; moreover, diachronic observation indicated that the engulfed COM crystals were subdivided during Mφ division and eliminated by the 7th day of culture. Additionally, imaging cytometry showed that the fluorescence level of f-COM crystals in the nigericin (-) group after 48 h was significantly lower than that in the nigericin (+) group.

Conclusions: This study confirmed active phagocytosis and lysosomal processing of engulfed COM crystals by Mφs. This discovery is expected to contribute to the development of future drugs that enhance the COM crystal phagocytic ability of Mφs.
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http://dx.doi.org/10.1159/000501965DOI Listing
March 2020

Deregulated MTOR (mechanistic target of rapamycin kinase) is responsible for autophagy defects exacerbating kidney stone development.

Autophagy 2020 04 29;16(4):709-723. Epub 2019 Jun 29.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.

Kidney stone disease is a lifestyle-related disease prevalent in developed countries; however, effective medical treatment for the disease is not yet well established. As cellular damage in renal tubular cells (RTCs) is responsible for the disease, here, we focused on the role of macroautophagy/autophagy in RTCs. We found that autophagic activity was significantly decreased in mouse RTCs exposed to calcium oxalate (CaOx) monohydrate crystals and in the kidneys of GFP-conjugated MAP1LC3B (microtubule- associated protein 1 light chain 3 beta) transgenic mice with CaOx nephrocalcinosis induced by glyoxylate. This caused accumulation of damaged intracellular organelles, such as mitochondria and lysosomes, the normal functioning of which is mediated by functional autophagy. An impairment of autophagy was also observed in the mucosa with plaques of CaOx kidney stone formers. We determined that the decrease in autophagy was caused by an upregulation of MTOR (mechanistic target of rapamycin kinase), which consequently resulted in the suppression of the upstream autophagy regulator TFEB (transcription factor EB). Furthermore, we showed that an MTOR inhibitor could recover a decrease in autophagy and alleviate crystal-cell interactions and the formation of crystals associated with increased inflammatory responses. Taken together, we conclude that autophagy compromised by MTOR deregulation is a fundamental feature in the pathology of kidney stone formation, and propose that chemical inhibition of MTOR could be a prospective strategy for disease suppression.: ACTB: actin, beta; CaOx: calcium oxalate; CKD: chronic kidney disease; COM: calcium oxalate monohydrate; LGALS3/galectin-3: lectin, galactose binding, soluble 3; GFP: green fluorescent protein; GOX: glyoxylate; HE: hematoxylin and eosin; MAPLC3B: microtubule- associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; NAC: N-acetyl-L-cysteine; ROS: reactive oxygen species; RTC: renal tubular cell; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TEM: transmission electron microscopy; tfLC3: tandem fluorescent-tagged LC3; 3-MA: 3-methyladenine.
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http://dx.doi.org/10.1080/15548627.2019.1635382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138204PMC
April 2020

Brown adipocytes and β-stimulant-induced brown-like adipocytes contribute to the prevention of renal crystal formation.

Am J Physiol Renal Physiol 2019 06 17;316(6):F1282-F1292. Epub 2019 Apr 17.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.

According to recent studies, kidney stones are associated with metabolic syndrome. We focused on brown adipocytes and β-stimulant-induced brown-like adipocytes to investigate how these adipocytes influence kidney stone disease. For the interscapular brown adipose tissue (iBAT) removal experiment, mice were subjected to either iBAT removal or sham operation (X-BAT group or sham group), and, after 3 wk, renal crystal deposition was induced by intra-abdominal injection of glyoxylate (GOX) for 6 days. For the β-stimulant experiment, mice were administered intra-abdominal injections of the β-stimulant (β-group) or saline (control group) for 6 days. Thereafter, renal crystal deposition was induced by intra-abdominal injection of GOX for 6 days. iBAT removal decreased the expression of and increased that of chemokine (C-C motif) ligand 2 (), EGF module-containing mucin-like receptor 1 (), and tumor necrosis factor () in the kidneys. Renal crystal deposition was 2.06-fold higher in the X-BAT group than in the sham group. The β-stimulant caused differentiation of white adipocytes into brown-like adipocytes. In the kidneys of the β-group, the expression of and decreased and that of increased. Renal crystal deposition was 0.17-fold lower in the β-group than in the control group. In summary, iBAT removal promoted kidney inflammation and renal crystal formation. β-Stimulant-induced brown-like adipocytes reduced inflammation and improved antioxidant action in the kidneys, which suppressed renal crystal formation. This is the first report on the therapeutic role of brown and brown-like adipocytes for kidney stone formation.
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http://dx.doi.org/10.1152/ajprenal.00523.2018DOI Listing
June 2019

Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population.

J Am Soc Nephrol 2019 05 11;30(5):855-864. Epub 2019 Apr 11.

Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan;

Background: A family history of urolithiasis is associated with a more than doubling of urolithiasis risk, and a twin study estimating 56% heritability of the condition suggests a pivotal role for host genetic factors. However, previous genome-wide association studies (GWAS) have identified only six risk-related loci.

Methods: To identify novel urolithiasis-related loci in the Japanese population, we performed a large-scale GWAS of 11,130 cases and 187,639 controls, followed by a replication analysis of 2289 cases and 3817 controls. Diagnosis of urolithiasis was confirmed either by a clinician or using medical records or self-report. We also assessed the association of urolithiasis loci with 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits (such as body mass index, lipid storage, eGFR, serum uric acid, and serum calcium), using up to 160,000 samples from BioBank Japan.

Results: The analysis identified 14 significant loci, including nine novel loci. Ten regions showed a significant association with at least one quantitative trait, including metabolic, kidney-related, and electrolyte traits, suggesting a common genetic basis for urolithiasis and these quantitative traits. Four novel loci were related to metabolic traits, obesity, hypertriglyceridemia, or hyperuricemia. The remaining ten loci were associated with kidney- or electrolyte-related traits; these may affect crystallization. Weighted genetic risk score analysis indicated that the highest risk group (top 20%) showed an odds ratio of 1.71 (95% confidence interval, 1.42 to 2.06) - 2.13 (95% confidence interval, 2.00 to 2.27) compared with the reference group (bottom 20%).

Conclusions: Our findings provide evidence that host genetic factors related to regulation of metabolic and crystallization pathways contribute to the development of urolithiasis.
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http://dx.doi.org/10.1681/ASN.2018090942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493984PMC
May 2019

Helper T-cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques.

Int J Urol 2019 06 28;26(6):670-677. Epub 2019 Mar 28.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Objectives: To elucidate the difference in the lithogenesis of calcium oxalate and calcium phosphate stones.

Methods: Renal papillary tissues were obtained from 23 idiopathic calcium oxalate and seven calcium phosphate stone patients who had undergone endoscopic lithotripsy. Samples were individually collected from two different regions in each patient: the papillary mucosa containing Randall's plaque and mucosa not containing Randall's plaque. A microarray analysis was carried out on those tissues to compare their gene expression patterns. Furthermore, a causal pathway analysis comparing their differences was carried out.

Results: Cluster analysis showed that gene expression profiles of calcium phosphate stone patients markedly differed from those of calcium oxalate stone patients. Disease and function analysis showed that Randall's plaque-containing tissues of calcium phosphate stone-forming patients had significantly higher movement and migration of mononuclear leukocytes, and lower tendency toward infection and lymph node formation than Randall's plaque-containing tissues of calcium oxalate stone formers. Additional pathway analysis showed increased immune cell signaling in calcium phosphate formers, such as the helper T cell 1 and 2 pathways, which was confirmed by their messenger ribonucleic acid expression.

Conclusions: The present results show the upregulation of helper T-cell signaling pathways in Randall's plaque-containing papillae in calcium phosphate, but not in calcium oxalate stone formers. Thus, helper T-cell immune responses and the related inflammatory processes seem to lead to the formation of calcium phosphate stones on Randall's plaques.
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http://dx.doi.org/10.1111/iju.13950DOI Listing
June 2019

Identification of new urinary risk markers for urinary stones using a logistic model and multinomial logit model.

Clin Exp Nephrol 2019 May 18;23(5):710-716. Epub 2019 Jan 18.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.

Background: Risk assessment for urinary stones has been mainly based on urinary biochemistry. We attempted to identify the risk factors for urinary stones by statistically analyzing urinary biochemical and inflammation-related factors.

Methods: Male participants (age, 20-79 years) who visited Nagoya City University Hospital were divided into three groups: a control group (n = 48) with no history of stones and two stone groups with calcium oxalate stone experience (first-time group, n = 22; recurring group, n = 40). Using 25-µL spot urine samples, we determined the concentrations of 18 candidate urinary proteins, using multiplex analysis on a MagPix® system.

Results: In univariate logistic regression models classifying the control and first-time groups, interleukin (IL)-1a and IL-4 were independent factors, with significantly high areas under the receiver operating characteristic curve (1.00 and 0.87, respectively, P < 0.01 for both). The multivariate models with IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) showed higher areas under the receiver operating characteristic curve (0.93) compared to that for the univariate model with IL-4. In the classification of control, first-time, and recurrence groups, accuracy was the highest for the multinomial logit model with IL-4, GM-CSF, IL-1b, IL-10, and urinary magnesium (concordance rate 82.6%).

Conclusions: IL-4, IL-1a, GM-CSF, IL-1b, and IL-10 were identified as urinary inflammation-related factors that could accurately distinguish control individuals from patients with urinary stones. Thus, the combined analysis of urinary biochemical data could provide an index that more clearly evaluates the risk of urinary stone formation.
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http://dx.doi.org/10.1007/s10157-019-01693-xDOI Listing
May 2019

Nationwide Increase in Cryptorchidism After the Fukushima Nuclear Accident.

Urology 2018 Aug 8;118:65-70. Epub 2018 May 8.

Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Objective: To estimate the change of discharge rate after cryptorchidism surgery between pre- and postdisaster in Japan. Cryptorchidism cannot be diagnosed before birth and is not a factor that would influence a woman's decision to seek an abortion. Therefore, this disease is considered suitable for assessing how the Great East Japan Earthquake and the subsequent Fukushima Daiichi nuclear accident (2011) influenced congenital diseases.

Materials And Methods: We obtained cryptorchidism discharge data collected over 6 years from hospitals that were included in an impact assessment survey of the Diagnosis Procedure Combination survey database in Japan and used these data to estimate the discharge rate after cryptorchidism surgery before and after the disaster. The 94 hospitals in Japan that participated in Diagnosis Procedure Combination system and had 10 or more discharges after cryptorchidism surgery within successive 6 years covering pre- and postdisaster period (FY2010-FY2015) were involved. The change in discharge rate between pre- and postdisaster was analyzed using a Bayesian generalized linear mixed model.

Results: Nationwide, a 13.4% (95% credible interval 4.7%-23.0%) increase in discharge rates was estimated. The results of all sensitivity analyses were similar to the reported main results.

Conclusion: The discharge rate of cryptorchidism was increased nationwide. The rates of low-weight babies or preterm births, risk factors of cryptorchidism, were almost constant during the study period, and age distribution of the surgery was also not changed, which suggested that the other factors that associated with the disaster increased the incidence of cryptorchidism.
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http://dx.doi.org/10.1016/j.urology.2018.04.033DOI Listing
August 2018

Kidney stone formers have more renal parenchymal crystals than non-stone formers, particularly in the papilla region.

BMC Urol 2018 Mar 12;18(1):19. Epub 2018 Mar 12.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.

Background: We investigated the renoprotective ability of healthy people against kidney stone formation. To clarify intratubular crystal kinetics and processing in human kidneys, we performed a quantitative and morphological observation of nephrectomized renal parenchyma tissues.

Methods: Clinical data and pathological samples from 60 patients who underwent radical nephrectomy for renal cancer were collected from June 2004 to June 2010. The patients were retrospectively classified as stone formers (SFs; n = 30, kidney stones detected by preoperative computed tomography) and non-stone formers (NSFs; n = 30, no kidney stone history). The morphology of parenchymal intratubular crystals and kidney stone-related gene and protein expression levels were examined in noncancerous renal sections from both groups.

Results: SFs had a higher smoking rate (P = 0.0097); lower red blood cell, hemoglobin, and hematocrit values; and higher urinary red blood cell, white blood cell, and bacterial counts than NSFs. Scanning electron microscopy revealed calcium-containing crystal deposits and crystal attachment to the renal tubular lumen in both groups. Both groups demonstrated crystal transmigration from the tubular lumen to the interstitium. The crystal diffusion analysis indicated a significantly higher crystal existing ratio in the medulla and papilla of SFs and a significantly higher number of papillary crystal deposits in SFs than NSFs. The expression analysis indicated relatively high osteopontin and CD68, low superoxide dismutase, and significantly lower Tamm-Horsfall protein expression levels in SFs. Multivariate logistic regression analysis involving the above factors found the presence of renal papillary crystals as a significant independent factor related to SFs (odds ratio 5.55, 95% confidence interval 1.08-37.18, P = 0.0395).

Conclusions: Regardless of stone formation, intratubular crystals in the renal parenchyma seem to transmigrate to the interstitium. SFs may have reduced ability to eliminate renal parenchymal crystals, particularly those in the papilla region, than NSFs with associated gene expression profiles.
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http://dx.doi.org/10.1186/s12894-018-0331-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848581PMC
March 2018

Genetic differences in C57BL/6 mouse substrains affect kidney crystal deposition.

Urolithiasis 2018 Nov 23;46(6):515-522. Epub 2018 Jan 23.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.

We previously established an experimental model of calcium oxalate crystal deposition in the mouse kidney using C57BL/6 mice. C57BL/6J (B6J) and C57BL/6N (B6N) are two core substrains of C57BL/6 mice. B6J and B6N substrains have approximately the same genomic sequence. However, in whole-genome analyses, substrains have slight genetic differences in some genes. In this study, we used these substrains as kidney crystal formation models and compared their genetic backgrounds to elucidate the pathogenic mechanisms of kidney stone formation. Eight-week-old male B6J and B6N mice (n = 15 in each group) were administered 80 mg/kg glyoxylate for 12 days, and the amount of kidney crystal depositions was compared. The expression levels of six genes (Snap29, Fgf14, Aplp2, Lims1, Naaladl2, and Nnt) were investigated by quantitative polymerase chain reaction, and the protein levels were evaluated by western blotting and immunohistochemistry. The amount of kidney crystal depositions was significantly higher in B6J mice than in B6N mice on days 6 and 12. The expression of nicotinamide nucleotide transhydrogenase (Nnt) gene was significantly lower in B6J mice than in B6N mice. The expression of Nnt protein was observed only in B6N mice, and preferential high expression was seen in renal tubular epithelial cells. The results of this study provide compelling evidence that differences in mouse substrains affect kidney crystal deposition and that the absence of Nnt protein could be involved in crystal formation in B6J mice.
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http://dx.doi.org/10.1007/s00240-018-1040-3DOI Listing
November 2018

A kit ligand, stem cell factor as a possible mediator inducing overactive bladder.

Neurourol Urodyn 2018 04 7;37(4):1258-1265. Epub 2017 Nov 7.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Objective: To investigate whether c-kit ligand, stem cell factor (SCF) affects the biological behavior of overactive bladder (OAB) and discuss the role of SCF as a possible mediator inducing OAB.

Materials And Methods: First, we performed an immunohistochemical study to examine the localization of SCF in the guinea pig and human bladder. Next, urinary SCF levels were measured in patients with OAB and in control subjects to evaluate a potential biomarker for the diagnosis of OAB. Third, we examined the effect of SCF administration on the urinary bladder using guinea pigs to obtain additional information about SCF. The animals were administered with mouse SCF, and cystometry was performed. The following urodynamic parameters were analyzed: inter-contraction interval, maximum voiding pressure, pressure threshold, detrusor baseline pressure, and the number of non-voiding contractions.

Results: Immunohistochemical study showed that the expression of SCF was observed throughout the bladder wall, but especially in the urothelium of guinea pig and human bladder. Medians and IQRs of urinary SCF and SCF/creatinine levels in OAB patients (85.9 pg/mL [42.8, 199.0] and 1.30 [0.56, 2.71], respectively) were significantly higher than in control subjects (18.9 pg/mL [5.0, 43.6] and 0.26 [0.13, 0.43], respectively). SCF administration dose-dependently shortened the intercontraction interval and an increased number of non-voiding contractions (P < 0.05).

Conclusions: Our present data suggest that SCF produced in the urinary bladder may act as a possible mediator by binding to c-kit, which is expressed in ICC-like cells in the suburothelial and muscle layers, to control bladder function.
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http://dx.doi.org/10.1002/nau.23449DOI Listing
April 2018

A New Navigation System of Renal Puncture for Endoscopic Combined Intrarenal Surgery: Real-time Virtual Sonography-guided Renal Access.

Urology 2017 Nov 4;109:44-50. Epub 2017 Aug 4.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuhoku, Nagoya City, Japan.

Objective: To evaluate the clinical utility of a new navigation technique for percutaneous renal puncture using real-time virtual sonography (RVS) during endoscopic combined intrarenal surgery.

Materials And Methods: Thirty consecutive patients who underwent endoscopic combined intrarenal surgery for renal calculi, between April 2014 and July 2015, were divided into the RVS-guided puncture (RVS; n = 15) group and the ultrasonography-guided puncture (US; n = 15) group. In the RVS group, renal puncture was repeated until precise piercing of a papilla was achieved under direct endoscopic vision, using the RVS system to synchronize the real-time US image with the preoperative computed tomography image. In the US group, renal puncture was performed under US guidance only. In both groups, 2 urologists worked simultaneously to fragment the renal calculi after inserting the miniature percutaneous tract. The mean sizes of the renal calculi in the RVS and the US group were 33.5 and 30.5 mm, respectively.

Results: A lower mean number of puncture attempts until renal access through the calyx was needed for the RVS compared with the US group (1.6 vs 3.4 times, respectively; P = .001). The RVS group had a lower mean postoperative hemoglobin decrease (0.93 vs 1.39 g/dL, respectively; P = .04), but with no between-group differences with regard to operative time, tubeless rate, and stone-free rate. None of the patients in the RVS group experienced postoperative complications of a Clavien score ≥2, with 3 patients experiencing such complications in the US group.

Conclusion: RVS-guided renal puncture was effective, with a lower incidence of bleeding-related complications compared with US-guided puncture.
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http://dx.doi.org/10.1016/j.urology.2017.06.040DOI Listing
November 2017

Determinants of health-related quality of life for patients after urinary lithotripsy: ureteroscopic vs. shock wave lithotripsy.

Urolithiasis 2018 Apr 29;46(2):203-210. Epub 2017 Mar 29.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.

Purpose: To compare the longitudinal health-related quality of life (HRQoL) after surgical intervention with ureteroscopic lithotripsy (URSL) and shock wave lithotripsy (SWL) and to evaluate the factors affecting HRQoL in urolithiasis patients.

Methods: A total of 262 patients who underwent lithotripsy (SWL, n = 61; URSL, n = 201) for upper urinary tract calculi treatment between June 2012 and January 2015 were evaluated. All patients were administered the Short-Form 36-item survey (SF-36) to assess HRQoL at four timepoints: before surgery, on the day of discharge, and 1 and 6 months after lithotripsy. Stone-free rates, complications, and analgesic requirements were evaluated to compare the effects of the two procedures on HRQoL.

Results: At the day of discharge, patients in the URSL group had significantly lower mean scores on five different subscales of the SF-36 questionnaire, namely, physical functioning, role-physical, social functioning, role-emotional, and mental health. The stone-free rate at 3 months after lithotripsy was significantly lower in the SWL group (72.1% vs. URSL, 93.0%; p < 0.001). The hospital stay was shorter in the SWL group (2.1 ± 0.07 vs. URSL, 4.1 ± 0.13 days; p < 0.001), and the analgesia requirements were also lower in the SWL group (0.3 ± 0.08 vs. URSL, 0.9 ± 0.20; p < 0.001).

Conclusions: The post-lithotripsy HRQoL was superior for SWL compared to URSL on the discharge date despite the lower stone-free rate of the former. The longer hospital stay and higher postoperative pain appeared to be the determinants of the lower HRQoL in the URSL group.
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http://dx.doi.org/10.1007/s00240-017-0972-3DOI Listing
April 2018

Response to Re: Potassium-sodium citrate prevents the development of renal microcalculi into symptomatic stones in calcium stone-forming patients.

Int J Urol 2017 04 16;24(4):334-335. Epub 2017 Feb 16.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.

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http://dx.doi.org/10.1111/iju.13309DOI Listing
April 2017

Genomic Landscape of Experimental Bladder Cancer in Rodents and Its Application to Human Bladder Cancer: Gene Amplification and Potential Overexpression of Cyp2a5/CYP2A6 Are Associated with the Invasive Phenotype.

PLoS One 2016 30;11(11):e0167374. Epub 2016 Nov 30.

Division of Cancer Development System, National Cancer Center Research Institute, Tokyo, Japan.

Non-muscle invasive (superficial) bladder cancer is a low-grade malignancy with good prognosis, while muscle invasive (invasive) bladder cancer is a high-grade malignancy with poor prognosis. N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) induces superficial bladder cancers with papillary morphology in rats and invasive bladder cancers with infiltrating phenotype in mice. In this study, we analyzed genomic landscapes of rodent BBN-induced bladder cancers using array-based comparative genomic hybridization (array CGH). While no significant copy number alterations were detected in superficial bladder tumors in rats, copy number gains in chromosomal regions 2D-E1, 7qA3, 9F2, and 11C-D were detected in invasive bladder tumors in mice. Amplification of representative genes located on 2D-E1 and 7qA3 chromosomal regions was confirmed by quantitative PCR. Cyp2a22 and Cyp2a5 genes but not Cyp2g1, Cyp2a12, and Rab4b genes on mouse chromosome 7qA3 were amplified in invasive bladder cancers. Although the human ortholog gene of Cyp2a22 has not been confirmed, the mouse Cyp2a5 gene is the ortholog of the human CYP2A6 gene located in chromosomal region 19q13.2, and CYP2A6 was identified by database search as one of the closest human homolog to mouse Cyp2a22. Considering a possibility that this region may be related to mouse 7qA3, we analyzed CYP2A6 copy number and expression in human bladder cancer using cell lines and resected tumor specimens. Although only one of eight cell lines showed more than one copy increase of the CYP2A6 gene, CYP2A6 amplification was detected in six out of 18 primary bladder tumors where it was associated with the invasive phenotype. Immunohistochemical analyses of 118 primary bladder tumors revealed that CYP2A6 protein expression was also higher in invasive tumors, especially in those of the scattered type. Together, these findings indicate that the amplification and overexpression of the CYP2A6 gene are characteristic of human bladder cancers with increased malignancy and that CYP2A6 can be a candidate prognostic biomarker in this type of cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167374PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130269PMC
July 2017

Potassium-sodium citrate prevents the development of renal microcalculi into symptomatic stones in calcium stone-forming patients.

Int J Urol 2017 01 17;24(1):75-81. Epub 2016 Oct 17.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.

Objectives: To evaluate the effect of potassium-sodium citrate on the development of computed tomography-detected renal microcalculi into symptomatic stones in calcium stone-forming patients.

Methods: Patients (aged 20-80 years) with history of calcium component stones who visited Nagoya City Hospital, Nagoya, Aichi, Japan, between April 2009 and June 2014 were included. They were retrospectively divided into those who did not receive potassium-sodium citrate (non-citrate group, n = 157) and those who did (citrate group, n = 60). For patients in both groups, we evaluated blood and urine biochemistry and sediment, number of computed tomography-detected microcalculi, number of asymptomatic microcalculi disappearances, and pain events. Observations were made at study initiation and 12 months later.

Results: The citrate group showed a significantly increased urine pH (P < 0.001) and daily citrate excretion (P < 0.001) over the study period. The non-citrate group showed increased numbers of microcalculi at study completion (P = 0.002); over the same period, the number of microcalculi in the citrate group decreased significantly (P = 0.03). Additionally, multivariable analysis showed more asymptomatic microcalculi disappearances (odds ratio 2.84, 95% confidence interval 1.49-5.39) and fewer pain events (odds ratio 0.37, 95% confidence interval 0.16-0.72) in the citrate group than in the non-citrate group. A sex-adjusted analysis showed more asymptomatic microcalculi disappearances (odds ratio 3.96, 95% confidence interval 1.57-10.02) and fewer pain events (odds ratio 0.22, 95% confidence interval 0.07-0.70) in women than in men after citrate treatment.

Conclusions: Potassium-sodium citrate prevents the development of renal microcalculi into symptomatic stones in calcium stone-forming individuals.
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http://dx.doi.org/10.1111/iju.13242DOI Listing
January 2017

M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development.

Sci Rep 2016 10 12;6:35167. Epub 2016 Oct 12.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

In our previous report, M2-macrophage (Mφs) deficient mice showed increased renal calcium oxalate (CaOx) crystal formation; however, the role of Mφs-related-cytokines and chemokines that affect kidney stone formation remains unknown. Here, we investigated the role of M1/M2s in crystal development by using in vitro and in vivo approaches. The crystal phagocytic rate of bone marrow-derived M2Mφs was higher than that of bone marrow-derived Mφs and M1Mφs and increased on co-culture with renal tubular cells (RTCs). However, the amount of crystal attachment on RTCs reduced on co-culture with M2Mφs. In six hyperoxaluric C57BL/6J mice, M1Mφ transfusion and induction by LPS and IFN-γ facilitated renal crystal formation, whereas M2Mφ transfusion and induction by IL-4 and IL-13 suppressed renal crystal formation compared with the control. These M2Mφ treatments reduced the expression of crystal-related genes, such as osteopontin and CD44, whereas M1Mφ treatment increased the expression of pro-inflammatory and adhesion-related genes such as IL-6, inducible NOS, TNF-α, C3, and VCAM-1. The expression of M2Mφ-related genes was lower whereas that of M1Mφ-related genes was higher in papillary tissue of CaOx stone formers. Overall, our results suggest that renal crystal development is facilitated by M1Mφs, but suppressed by M2Mφs.
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http://dx.doi.org/10.1038/srep35167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059697PMC
October 2016

Pathophysiology-based treatment of urolithiasis.

Int J Urol 2017 01 18;24(1):32-38. Epub 2016 Aug 18.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Urolithiasis, a complex multifactorial disease, results from interactions between environmental and genetic factors. Epidemiological studies have shown the association of urolithiasis with a number of lifestyle-related diseases, including cardiovascular diseases, hypertension, chronic kidney disease, diabetes and metabolic syndrome. Elucidation of the mechanisms underlying urinary stone formation will enable development of new preventive treatments. The present article reviews the epidemiology, pathophysiology and potential treatment of urolithiasis. Recent literature has shown that oxidative stress and reactive oxygen species could be one such mechanistic pathway. Calcium oxalate crystals adhering to renal tubular cells are incorporated into the cells through the involvement of osteopontin. Stimulation of crystal-cell adhesion impairs acceleration of the mitochondrial permeability transition pore in tubular cells, resulting in mitochondrial collapse, oxidative stress and activation of the apoptotic pathway in the initial steps of renal calcium crystallization. With regard to genetic factors, studies show that single nucleotide polymorphisms in genes encoding calcium-sensing receptor, vitamin D receptor and osteopontin are correlated with urolithiasis. Genome-wide association studies have shown that CLDN14 and NPT2 are associated with urolithiasis in Caucasian and Japanese populations, respectively. Thus, single nucleotide polymorphism analysis would aid in the prediction of urolithiasis risk and recurrence. New diagnostic methods and preventive approaches, along with complete removal of stones, will improve the management of urolithiasis.
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http://dx.doi.org/10.1111/iju.13187DOI Listing
January 2017

Robot-assisted laparoscopic pyeloplasty for ureteropelvic junction obstruction: comparison between pediatric and adult patients-Japanese series.

J Robot Surg 2017 Jun 6;11(2):151-157. Epub 2016 Aug 6.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.

Robotic-assisted procedures are gaining traction as a viable form of minimally invasive surgery in the field of reconstructive surgery. In this article, the aim is to present our initial experience and clinical outcomes of robot-assisted laparoscopic pyeloplasty (RAL-P). We performed RAL-P in 22 patients for the management of ureteropelvic junction obstruction between December 2012 and August 2015. The da Vinci® S surgical system was utilized for all cases. All procedures were performed via a transperitoneal approach. We assessed perioperative outcomes, and furthermore, compared between pediatric and adult patients undergoing this procedure. Dismembered procedures were performed in 19 patients. Three patients underwent Y-V plasty, and two patients who experienced failure during the primary pyeloplasty had to undergo reoperation. Although the console time for pediatric patients was significantly shorter than that of adults (123.1 ± 18.3, 162.4 ± 23.9 min, respectively, p < 0.001), success rate was not significantly different between pediatric and adults (100 vs 90 %, p = 0.512). According to a comparison of surgical outcomes by age, the console time was significantly shorter in pediatric than in adult patients. This finding may be attributable to the differences in intraabdominal fatty tissues. Besides, RAL-P with Y-V plasty was applicable even for cases of failed pyeloplasty. In conclusion, the surgical outcomes of RAL-P were favorable and safe for both pediatric and adult patients, and comparable to findings of previous reports. To our knowledge, this is the first report of a case series of RAL-P in Japan.
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http://dx.doi.org/10.1007/s11701-016-0633-5DOI Listing
June 2017

Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers.

J Am Soc Nephrol 2017 Jan 13;28(1):333-347. Epub 2016 Jun 13.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.

Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.
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http://dx.doi.org/10.1681/ASN.2015111271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198277PMC
January 2017

Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents.

PPAR Res 2016 28;2016:9605890. Epub 2016 Feb 28.

Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.

Peroxisome proliferator-activated receptors (PPARs) and related inflammatory and oxidative molecule expression were investigated in a hyperoxaluric rodent model to evaluate the in vivo efficacy of PPAR agonists in preventing renal crystal formation. PPAR expression was examined in a mouse hyperoxaluria kidney stone model induced by daily intra-abdominal glyoxylate injection. Therapeutic effects of the PPARα agonist fenofibrate and PPARγ agonist pioglitazone were also assessed in a 1% ethylene glycol-induced rat model of hyperoxaluria. Crystal formation, inflammation, cell injury, apoptosis, and oxidative stress were compared to those of vehicle-treated controls. Quantitative reverse transcription-polymerase chain reaction revealed that PPARα and PPARγ expression decrease and increase, respectively, during crystal formation in hyperoxaluric kidneys. In addition, PPARα localized to the cytoplasm of both proximal and distal tubular cells, whereas PPARγ accumulated in the nucleus of proximal tubular cells. Furthermore, renal crystal formation was significantly less prevalent in pioglitazone-treated rats but higher in the fenofibrate-treated and fenofibrate/pioglitazone-cotreated groups compared to controls, thus indicating that pioglitazone, but not fenofibrate, markedly decreased cell inflammation, oxidative stress, and apoptosis. Collectively, the results demonstrated that PPARγ suppressed renal crystal formation via its antioxidative and anti-inflammatory effects; however, the renotoxicity of PPARα may elicit the opposite effect.
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http://dx.doi.org/10.1155/2016/9605890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789040PMC
March 2016

Bacillus Calmette-Guerin therapy after the second transurethral resection significantly decreases recurrence in patients with new onset high-grade T1 bladder cancer.

BMC Urol 2016 Feb 27;16. Epub 2016 Feb 27.

Department of Nephro-Urology, Nagoya City University, Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, 467-8601, Nagoya, Japan.

Background: The purpose of this study was to assess the efficacy of Bacillus Calmette-Guerin (BCG) therapy after a second transurethral resection (TUR) in new onset high-grade T1 bladder cancer.

Methods: From January 2008 to September 2013, 207 patients with new onset high-grade T1 bladder cancer after an initial TUR were treated at our university and at affiliated hospitals. Residual cancer rate, intravesical recurrence-free survival (RFS), and risk factors for intravesical recurrence were analyzed.

Results: Among a total of 207 patients, 42 patients were treated with BCG therapy following a second TUR (group 1), 23 were treated with second TUR alone (group 2), 72 were treated with BCG alone (group 3), and 70 were treated without a second TUR or BCG. The median patients' age was 72.0 years, and the median follow-up period was 33.5 months. The second TUR revealed that 34 patients (52 %) had residual cancer. Between groups 1 and 2 and groups 1 and 3, the differences in RFS were statistically significant (p = 0.002 and 0.045, respectively). In addition, BCG therapy was the most significant factor to predict RFS after the second TUR. Among the 31 patients whose pathology of the second TUR was pT0, only 1 of 12 patients (8 %) in group 1 and 11 of 19 patients (58 %) in group 2 had a recurrence.

Conclusions: BCG instillation following a second TUR decreases intravesical recurrence, even if the pathology of the second TUR is pT0.
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http://dx.doi.org/10.1186/s12894-016-0126-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769574PMC
February 2016

A Case of Metastatic Urothelial Carcinoma Treated with Pemetrexed as Third-Line Chemotherapy with Discussion and Literature Review.

Case Rep Oncol 2015 Sep-Dec;8(3):530-5. Epub 2015 Nov 1.

Department of Nephro-urology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.

Pemetrexed is an antifolate agent that is regarded as an alternative second-line chemotherapy against advanced or metastatic urothelial carcinoma (UC). However, there is limited information on pemetrexed in a third-line setting. We report a case of metastatic UC treated with pemetrexed as third-line chemotherapy following gemcitabine and cisplatin (GC) and gemcitabine and docetaxel (GD) therapies. A 73-year-old man with a history of transurethral resection of bladder carcinoma presented with pollakiuria. CT revealed a mass in the left renal pelvis that had invaded into the parenchyma of the left kidney, as well as para-aortic and mediastinum lymph node enlargement. Urinary cytology of the lesion in the left renal pelvis revealed UC. Thus, the patient was diagnosed with left renal pelvic carcinoma (cT3N2M0). After having received 4 courses of GC therapy, another mediastinum lymph node was enlarged. He subsequently received 3 courses of GD therapy as second-line chemotherapy, which showed little efficacy against the metastatic lesions. The patient was administered 3 courses of pemetrexed as third-line chemotherapy; however, its effect on tumor reduction was not sufficient. Finally, metastasis to the liver was observed, and he died 21 months after initiation of chemotherapy. For pathological confirmation, needle biopsy of a metastatic lymph node performed after death revealed high-grade UC and a high positivity of programmed death ligand 1 (PD-L1) in the tumor, which suggested that he could have benefited from anti-PD-L1 antibody immunotherapy. This report describes the outcome of pemetrexed treatment and proposes another possible candidate as third-line chemotherapy against metastatic UC.
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http://dx.doi.org/10.1159/000442347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677708PMC
December 2015

Laparoscopic Versus Open Radical Cystectomy for Patients Older than 75 Years: a Single-Center Comparative Analysis.

Asian Pac J Cancer Prev 2015 ;16(15):6353-8

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan E-mail :

Background: To explore the safety, efficacy, and oncological outcome of 3-port laparoscopic radical cystectomy (LRC) compared to open radical cystectomy (ORC) in patients older than 75 years.

Materials And Methods: From June 2010 to July 2014, we analyzed 16 radical cystectomies in patients older than 75 years (LRC group=8; ORC group=8). Demographic parameters, operative variables, and perioperative outcome in the 2 groups were retrospectively collected, analyzed, and compared.

Results: Patients in both groups had comparable preoperative characteristics. A significantly longer operating time (476 vs. 303 min, P=0.0002) and less estimated blood loss (627 vs. 2,106 mL, P=0.021) were observed in the LRC group compared to the ORC group. Infection and ileus were the most common early complications after surgery. Patients who underwent ORC suffered from more postoperative infection (22.2% vs. 0.0%, P=0.054) and ileus (25.0% vs. 12.5%, P=0.521) than the LRC group, but the difference was not significant.

Conclusions: Judging from this initial trial, 3-port LRC can be safely carried out in elderly patients. We suggest 3-port LRC as the primary intervention to treat muscle-invasive or high-risk nonmuscle-invasive bladder cancer in elderly patients with an otherwise relatively long life expectancy.
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http://dx.doi.org/10.7314/apjcp.2015.16.15.6353DOI Listing
July 2016

Neuroendocrine Carcinoma of the Kidney and Bladder with Loss of Heterozygosity and Changes in Chromosome 3 Copy Number.

Am J Case Rep 2015 Sep 11;16:611-6. Epub 2015 Sep 11.

Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Background: Neuroendocrine carcinomas (NECs) of the urological organs are observed occasionally, although simultaneous development in the kidney and blabber has not been reported.

Case Report: We report a case of a metastatic NEC of the kidney and bladder in a 77-year-old woman who underwent renal biopsy and transurethral resection of the bladder tumor. Pathological examination revealed NEC in the kidney and the bladder samples. Immunohistochemical examination revealed strongly positive staining for synaptophysin, chromogranin A, and CD56, and focally positive staining for cytokeratin AE 1/3 and Cam 5.2. Fluorescence in situ hybridization confirmed the increased chromosome 3 copy number, and loss of hybridization in 3q21, 5q22-23, 10q26, and 13q14 was detected when the tumor samples were compared with normal samples.

Conclusions: This is a rare case of NEC-specific genetic abnormalities in a kidney-derived tumor, and is the first report to identify kidney-derived NEC that metastasized to the bladder via the urinary tract.
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http://dx.doi.org/10.12659/AJCR.894274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571826PMC
September 2015

MRI Findings of Inverted Urothelial Papilloma of the Bladder.

AJR Am J Roentgenol 2015 Aug;205(2):311-6

1 Department of Radiology, Nagoya City University Graduate School of Medical Sciences and Medical School, 1 Kawasumi Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.

Objective: The objective of this study was to characterize MRI findings of inverted urothelial papilloma of the bladder.

Materials And Methods: Data pertaining to 16 patients with 18 pathologically proven inverted urothelial papillomas of the bladder who had undergone MRI were retrospectively collected from seven institutions. The shape and surface characteristics of the tumors were evaluated using T2-weighted MR images. In addition, the signal intensity of inverted urothelial papillomas was visually assessed on T1-weighted, T2-weighted, and DW images and on early and delayed phase contrast-enhanced images.

Results: The shape of the 18 inverted urothelial papillomas of the bladder was classified as polypoid with a stalk for 16 tumors (89%) and polypoid without a stalk for two tumors (11%). All stalks were surrounded by urine in the bladder. A total of 15 of the tumor surfaces (83%) were nonpapillary and three (17%) were papillary. All 12 of the inverted urothelial papillomas for which evaluable T1-weighted images were available were isointense with the bladder wall. The lesions had a slightly higher signal intensity than the bladder wall in 15 of the patients (83%) and showed isointensity with the bladder wall in three patients (17%). A total of three patients (17%) had tiny hyperintense foci noted on T2-weighted images. All 16 of the inverted urothelial papillomas examined by DWI had very high signal intensity. All 13 of the lesions for which early phase images were obtained using dynamic contrast-enhanced MRI showed strong enhancement. When compared with early phase images, delayed phase images of the same 13 lesions showed that enhancement was stronger in two lesions (15%), similar in six lesions (46%), and weaker in five lesions (38%).

Conclusion: On MRI, the typical appearance of inverted urothelial papillomas of the bladder is a polypoid shape with a nonpapillary surface and a thin short stalk surrounded by urine. Cystic foci are also occasionally seen within the tumor.
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http://dx.doi.org/10.2214/AJR.14.13879DOI Listing
August 2015

Proinflammatory and Metabolic Changes Facilitate Renal Crystal Deposition in an Obese Mouse Model of Metabolic Syndrome.

J Urol 2015 Dec 17;194(6):1787-96. Epub 2015 Jul 17.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Purpose: To clarify metabolic syndrome induced stone formation mechanisms we investigated the metabolic and immunohistochemical characteristics associated with renal crystal deposition using a model of mice with metabolic syndrome administered a high fat diet and ethylene glycol.

Materials And Methods: Ob/Ob mice with Leptin gene deficiencies and metabolic syndrome related characteristics were compared with wild heterozygous lean mice. Four study groups were fed standard food and water (control group), a high fat diet and normal water (high fat diet group), 1% ethylene glycol and standard food (ethylene glycol group) or a high fat diet and 1% ethylene glycol (high fat diet plus ethylene glycol group). Blood, urine and kidney samples were taken after 14 days.

Results: Ob/Ob mice in the high fat diet plus ethylene glycol group showed diffuse renal crystal depositions. Lean and Ob/Ob mice in the high fat diet plus ethylene glycol group showed significant excretion of urinary calcium oxalate crystals. Ob/Ob mice had significant hypercalciuria, hyperphosphaturia and hyperlipidemia, massive lipid fragments in tubular lumina and fat droplets in renal tubular cells. Ob/Ob mice in the high fat diet plus ethylene glycol group had markedly increased expression of osteopontin, monocyte chemoattractant protein-1, interleukin-6 and tumor necrosis factor-α. In Ob/Ob mice the number of proinflammatory macrophages was considerably elevated.

Conclusions: We induced renal crystal deposition in mice with metabolic syndrome using a high fat diet and ethylene glycol. Increases in luminal mineral and lipid density, and proinflammatory adipocytokines and macrophages facilitated renal crystal formation in mice with metabolic syndrome.
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http://dx.doi.org/10.1016/j.juro.2015.07.083DOI Listing
December 2015

First case report of staghorn calculi successfully removed by mini-endoscopic combined intrarenal surgery in a 2-year-old boy.

Int J Urol 2015 Oct 2;22(10):978-80. Epub 2015 Jul 2.

Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Less-invasive therapy for pediatric urolithiasis is available due to the miniaturization of equipment and improved optics; however, surgical treatment strategies, especially for large calculi, remain controversial. We describe here our experience of treating a 2-year-old boy with left renal staghorn calculi with a single session of mini-endoscopic combined intrarenal surgery in the prone split-leg position with pre-ureteral stenting and the directional enhanced flow imaging ultrasound technique. This is the first report of successful pediatric mini-endoscopic combined intrarenal surgery without any major complications. We believe this technique provides an important therapeutic option for large renal calculus in pediatric patients.
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http://dx.doi.org/10.1111/iju.12860DOI Listing
October 2015

A Case of Renal Primitive Neuroectodermal Tumor Confirmed by Fluorescence in situ Hybridization.

Case Rep Oncol 2015 Jan-Apr;8(1):205-11. Epub 2015 Apr 28.

Department of Nephro-Urology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.

Primitive neuroectodermal tumor (PNET) is a member of the Ewing's sarcoma family of tumors (ESFT). We report a case of PNET in a 66-year-old male who presented with a large solid tumor within the parenchyma of the middle pole of the left kidney with metastases to the left adrenal gland and right ischium. A fine-needle biopsy was performed and showed a small round cell tumor. Results of immunohistochemical staining suggested this tumor belonged to ESFT. Preoperative VDC-IE (combined vincristine, doxorubicin and cyclophosphamide followed by another combination of ifosfamide and etoposide) chemotherapy and left radical nephrectomy and adrenalectomy were performed. The histopathological findings of the resected tumor were similar to those in the biopsy specimen, but the results of AE1/AE3 were different. For the diagnosis, fluorescence in situ hybridization was performed. Split signals of the EWSR1 gene were detected, and transmission electron microscopy showed neuroendocrine granules and microtubules. The final diagnosis of this tumor was PNET of the kidney.
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http://dx.doi.org/10.1159/000382118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448065PMC
June 2015
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