Publications by authors named "Nobuo Shinohara"

279 Publications

Associations among maternal perfluoroalkyl substance levels, fetal sex-hormone enzymatic gene polymorphisms, and fetal sex hormone levels in the Hokkaido study.

Reprod Toxicol 2021 Sep 16;105:221-231. Epub 2021 Sep 16.

Center for Environmental and Health Sciences, Hokkaido University, North-12, West-7, Kita-ku, Sapporo, 060-0812, Japan. Electronic address:

Prenatal sex hormones affect fetal growth; for example, prenatal exposure to low levels of androgen accelerates female puberty onset. We assessed the association of perfluoroalkyl substances (PFASs) in maternal sera and infant genotypes of genes encoding enzymes involved in sex steroid hormone biosynthesis on cord sera sex hormone levels in a prospective birth cohort study of healthy pregnant Japanese women (n = 224) recruited in Sapporo between July 2002 and October 2005. We analyzed PFAS and five sex hormone levels using liquid chromatography-tandem mass spectrometry. Cytochrome P450 (CYP) 17A1 (CYP17A1 rs743572), 19A1 (CYP19A1 rs10046, rs700519, and rs727479), 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1 rs6203), type 2 (HSD3B2 rs1819698, rs2854964, and rs4659175), 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1 rs605059, rs676387, and rs2676531), and type 3 (HSD17B3 rs4743709) were analyzed using real-time PCR. Multiple linear regression models were used to establish the influence of log-transformed PFAS levels and infant genotypes on log-transformed sex steroid hormone levels. When the interaction between perfluorooctanesulfonate (PFOS) levels and female infant genotype CYP17A1 (rs743572) on the androstenedione (A-dione) levels was considered, the estimated changes (95 % confidence intervals) in A-dione levels against PFOS levels, female infant genotype CYP17A1 (rs743572)-AG/GG, and interaction between them showed a mean increase of 0.445 (0.102, 0.787), mean increase of 0.392 (0.084, 0.707), and mean reduction of 0.579 (0.161, 0.997) (P = 0.007), respectively. Moreover, a female-specific interaction with testosterone levels was observed. A-dione and T levels showed positive main effects and negative interaction with PFOS levels and the female infant CYP17A1 genotype.
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http://dx.doi.org/10.1016/j.reprotox.2021.09.003DOI Listing
September 2021

Postoperative thyroid storm after radical nephrectomy for renal cell carcinoma with inferior vena cava tumor thrombus.

IJU Case Rep 2021 Sep 13;4(5):330-332. Epub 2021 Jul 13.

Departments of Department of Urology Hokkaido University Hospital Sapporo Japan.

Introduction: Thyroid storm is a rare life-threating condition. We report a case of thyroid storm after radical nephrectomy for renal cell carcinoma with inferior vena cava tumor thrombus.

Case Presentation: A 76-year-old man with a left renal tumor and tumor thrombus extending into the inferior vena cava underwent left radical nephrectomy and thrombectomy. After the surgery, his postoperative course rapidly deteriorated, including central nervous system disturbance, fever, tachycardia, congestive heart failure, and hepatic manifestation. Thyroid function test revealed perioperative hyperthyroidism. Corticosteroids and inorganic iodide improved his condition, suggesting that he developed thyroid storm after surgery. He was discharged 5 months after surgery and has been free from disease recurrence for more than 2 years.

Conclusion: Thyroid storm after surgery is rare. However, this postoperative complication is important because it is fatal if not diagnosed and treated properly.
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http://dx.doi.org/10.1002/iju5.12341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413219PMC
September 2021

A case of pubic osteomyelitis after implantation of an artificial urinary sphincter: A case report.

Low Urin Tract Symptoms 2021 Aug 25. Epub 2021 Aug 25.

Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Case: We describe a rare case of pubic osteomyelitis secondary to implantation of an artificial urinary sphincter (AUS). A 49-year-old man developed total urinary incontinence due to spinal cord injury 23 years earlier. After AUS implantation, he became continent. Fourteen years later, incontinence suddenly recurred.

Outcome: We planned to replace the dysfunctional AUS with a new one. We removed only the implanted control pump, leaving the urethral cuff at the bladder neck and pressure-regulating balloon to reduce surgical invasiveness, and performed AUS reimplantation. A new urethral cuff was placed around the bulbar urethra. Postoperatively, antibiotics, placement of a drainage catheter, and removal of the new AUS were required due to device infection. However, the infection persisted and magnetic resonance imaging showed inflammatory changes at the symphysis pubis, so osteotomy was performed to control infection. One year postoperatively, no gait disturbance or recurrence of pubic osteomyelitis was identified. AUS reimplantation was again performed and the patient is now socially continent.

Conclusions: We have reported a rare case of pubic osteomyelitis secondary to AUS implantation. Clinicians should suspect pubic osteomyelitis if infection persists.
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http://dx.doi.org/10.1111/luts.12409DOI Listing
August 2021

GRIK2 is a target for bladder cancer stem-like cell-targeting immunotherapy.

Cancer Immunol Immunother 2021 Aug 18. Epub 2021 Aug 18.

Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan.

Recent studies have revealed that treatment-resistant cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be targeted by cytotoxic T lymphocytes (CTLs). CTLs recognize antigenic peptides derived from tumor-associated antigens; thus, the identification of tumor-associated antigens expressed by CSCs/CICs is essential. Human leucocyte antigen (HLA) ligandome analysis using mass spectrometry enables the analysis of naturally expressed antigenic peptides; however, HLA ligandome analysis requires a large number of cells and is challenging for CSCs/CICs. In this study, we established a novel bladder CSC/CIC model from a bladder cancer cell line (UM-UC-3 cells) using an ALDEFLUOR assay. CSCs/CICs were isolated as aldehyde dehydrogenase (ALDH)-high cells and several ALDH clone cells were established. ALDH clone cells were enriched with CSCs/CICs by sphere formation and tumorigenicity in immunodeficient mice. HLA ligandome analysis and cap analysis of gene expression using ALDH clone cells revealed a distinctive antigenic peptide repertoire in bladder CSCs/CICs, and we found that a glutamate receptor, ionotropic, kainite 2 (GRIK2)-derived antigenic peptide (LMYDAVHVV) was specifically expressed by CSCs/CICs. A GRIK2 peptide-specific CTL clone recognized GRIK2-overexpressing UM-UC-3 cells and ALDH clone cells, indicating that GRIK2 peptide can be a novel target for bladder CSC/CIC-targeting immunotherapy.
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http://dx.doi.org/10.1007/s00262-021-03025-zDOI Listing
August 2021

Can ultrasound measurement of bladder wall thickness be a useful adjunct for regular urodynamics in children with spina bifida?

J Pediatr Urol 2021 Jul 13. Epub 2021 Jul 13.

Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Introduction: Spina bifida is a major cause of neurologic bladder dysfunction among children. The goal of neurogenic bladder treatment is to preserve renal function. Close follow-up is essential, as lower urinary tract functions can change with patient growth. Presently, invasive urodynamics is the gold standard for precisely assessing lower urinary tract function. Ultrasound is a low-cost, non-invasive, uncomplicated examination that can be easily repeated. Bladder wall thickness (BWT) measurement by ultrasound has been proposed as a non-invasive alternative for identifying lower urinary tract dysfunctions.

Objective: Currently there are few reports on BWT in children with spina bifida, and BWT assessment methodology has yet to be defined. The present study aim was to investigate whether BWT could be a useful adjunct for regular urodynamics in children with spina bifida. We especially focused on the precise bladder volume during BWT measurements that were simultaneously performed with urodynamics.

Study Design: This prospective observational study investigated 33 patients with spina bifida who underwent video urodynamics. We assessed BWT measurements using ultrasound simultaneously performed with video urodynamics. BWT was calculated for the ventral and dorsal walls at 0%, 20%, 40%, 60%, 80%, and 100% of the expected bladder capacity.

Results: Median of bladder capacity was 240 mL, and bladder compliance was 19.2 mL/cmHO. Detrusor overactivity was present in 66.7% and vesicoureteral reflux was present in 27.3% of the patients. BWT of the ventral wall was significantly lower than the dorsal wall. During increases in the bladder volume, both the ventral and dorsal walls exhibited proportional thinning (p < 0.05). There were no significant differences for BWT between males and females. Although there was a higher statistical tendency for detrusor overactivity versus without detrusor overactivity (p = 0.085), there were no significant differences found between patients with and without detrusor overactivity.

Discussion: This is the first report where multiple BWT measurements points with video urodynamics were simultaneously performed. Selection of bladder volumes for BWT measurements is critical. Our current study measured six points for each patient during urodynamics. However, available data was not sufficient for detecting bladder function. Until now, there has been no valid standard condition defined for measuring BWT and thus, lack of a standardized method has resulted in discrepancies among studies.

Conclusion: Our measurement conditions showed BWT may not correlate with the degree of bladder detrusor dysfunction. As BWT ultrasound cannot identify bladder dysfunction of children with spina bifida, this cannot be used as a substitute for invasive urodynamics.
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http://dx.doi.org/10.1016/j.jpurol.2021.07.007DOI Listing
July 2021

Prognostic value of programmed death-ligand 1 status in Japanese patients with renal cell carcinoma.

Int J Clin Oncol 2021 Jul 21. Epub 2021 Jul 21.

Department of Surgical Pathology, Aichi Medical University Hospital, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.

Background: Programmed death-ligand 1 (PD-L1) positivity is associated with poor prognosis in renal cell carcinoma (RCC). Because the prognostic impact and effect of confounding factors are less known, we investigated the prognostic significance of PD-L1 expression in Japanese patients with recurrent/metastatic RCC who started systemic therapy in 2010-2015.

Methods: This multicenter, retrospective study recruited patients from 29 Japanese study sites who had prior systemic therapy for RCC (November 2018 to April 2019) and stored formalin-fixed paraffin-embedded primary lesion samples. The primary outcome was overall survival (OS) by PD-L1 expression. Secondary outcomes included OS in subgroups and duration of first- and second-line therapies by PD-L1 expression. OS distributions were estimated using Kaplan-Meier methodology.

Results: PD-L1 expression (on immune cells [IC] ≥ 1%) was observed in 315/770 (40.9%) patients. PD-L1 positivity was more prevalent in patients with poor risk per both Memorial Sloan Kettering Cancer Center [MSKCC] and International Metastatic RCC Database Consortium, and high-risk pathological features (higher clinical stage, nuclear grade and sarcomatoid features). Median OS for PD-L1-positive patients was 30.9 months (95% CI 25.5-35.7) versus 37.5 months (95% CI 34.0-42.6) for PD-L1-negative patients (HR 1.04 [90% CI 0.89-1.22, p = 0.65]; stratified by MSKCC risk and liver metastases). Propensity score weight (PSW)-adjusted OS was similar between PD-L1-positive and -negative patients (median 34.4 versus 31.5 months; estimated PSW-adjusted HR 0.986).

Conclusions: This study suggests PD-L1 status was not an independent prognostic factor in recurrent/metastatic RCC during the study period because PD-L1 positivity was associated with poor prognostic factors, especially MSKCC risk status.
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http://dx.doi.org/10.1007/s10147-021-01993-xDOI Listing
July 2021

Fertility and reproductive technology use in testicular cancer survivors in Japan: A multi-institutional, cross-sectional study.

Int J Urol 2021 Jul 18. Epub 2021 Jul 18.

Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Objective: To evaluate fertility and use of reproductive technology of testicular cancer survivors in a multi-institutional, cross-sectional study.

Methods: This study recruited testicular cancer survivors who were followed after treatment for testicular cancer at eight high-volume institutions between 2018 and 2019. The participants completed the questionnaires on marital status, fertility and use of reproductive technology.

Results: A total of 567 testicular cancer survivors, with a median age of 43 years, responded to the questionnaire. Chemotherapy was given to 398 survivors, including three cycles of cisplatin-based chemotherapy in 106 patients and four cycles in 147 patients. Among 153 survivors who attempted sperm cryopreservation, 133 (87%) could preserve sperm. Of the 28 survivors whose cryopreserved sperm was used, 17 (61%) fathered children. Of the 72 survivors who fathered children without the use of cryopreserved sperm, 59 (82%) fathered naturally. Whereas 33 (20%) of 169 survivors treated without chemotherapy fathered children without using cryopreserved sperm, 39 (10%) of 398 treated with chemotherapy fathered children (P < 0.05). Furthermore, the paternity rate was 12% and 5% in testicular cancer survivors with three and four cycles of cisplatin-based chemotherapy, respectively (P < 0.05). However, of 121 survivors who wanted to have children, 14 (12%) received counseling about infertility treatment.

Conclusions: Testicular cancer survivors preserving their sperm have a higher paternity rate after chemotherapy, especially after four cycles, than those not using cryopreserved sperm. Physicians who give chemotherapy for testicular cancer need to take particular care not only with respect to recurrence of testicular cancer, but also to post-treatment fertility.
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http://dx.doi.org/10.1111/iju.14645DOI Listing
July 2021

Intravesical Bacillus Calmette-Guérin Treatment for T1 High-Grade Non-Muscle Invasive Bladder Cancer with Divergent Differentiation or Variant Morphologies.

Cancers (Basel) 2021 May 26;13(11). Epub 2021 May 26.

Department of Urology, Nara Medical University, Kashihara, Nara 634-8522, Japan.

The 2016 World Health Organization classification newly described infiltrating urothelial carcinoma (UC) with divergent differentiation (DD) or variant morphologies (VMs). Data comparing oncological outcomes after bladder-preservation therapy using intravesical Bacillus Calmette-Guérin (BCG) treatment among T1 bladder pure UC (pUC), UC with DD (UC-DD), and UC with VMs (UC-VM) are limited. We evaluated 1490 patients with T1 high-grade bladder UC who received intravesical BCG during 2000-2019. They were classified into three groups: 93.6% with pUC, 4.4% with UC-DD, and 2.0% with UC-VM. Recurrence-free, progression-free, and cancer-specific survival following intravesical BCG were compared among the groups using multivariate Cox regression analysis, also used to estimate inverse probability of treatment weighting-adjusted hazard ratio and 95% confidence interval for the outcomes. Glandular differentiation and micropapillary variant were the most common forms in the UC-DD and UC-VM groups, respectively. Of 1490 patients, 31% and 13% experienced recurrence and progression, respectively, and 5.0% died of bladder cancer. Survival analyses revealed the impact of concomitant VMs was significant for cancer-specific survival, but not recurrence-free and progression-free survival compared with that of pUC. Our analysis clearly demonstrated that concomitant VMs were associated with aggressive behavior in contrast to concomitant DD in patients treated with intravesical BCG.
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http://dx.doi.org/10.3390/cancers13112615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198171PMC
May 2021

Spontaneous closure of arteriovenous fistula after kidney transplantation.

Int J Urol 2021 Aug 19;28(8):872-873. Epub 2021 May 19.

Department of Urology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.

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http://dx.doi.org/10.1111/iju.14576DOI Listing
August 2021

Health-Related Quality of Life in Testicular Cancer Survivors in Japan: A Multi-Institutional, Cross-Sectional Study Using the EORTC QLQ-TC26.

Urology 2021 Mar 27. Epub 2021 Mar 27.

Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Urology, Miyagi Cancer Center, Natori, Japan.

Objective: To evaluate the health-related quality of life (QOL) of testicular cancer (TC) survivors using the Japanese version of the EORTC QLQ-TC26 questionnaire in a multi-institutional, cross-sectional study.

Methods: This study recruited TC survivors who were followed after treatment for TC at eight high-volume institutions between January, 2018 and March, 2019. The participants completed the EORTC QLQ-TC26 questionnaire and mailed the completed questionnaires to a central institution. The QOL scores were assessed according to therapeutic modality (watchful waiting, WW; chemotherapy, CT; and CT followed by retroperitoneal lymph node dissection, CT+RPLND) and follow-up period and compared using analysis of variance and Student's t-test.

Results: A total of 567 TC survivors responded to the questionnaire. The median age at response was 43 years (IQR 35-51 years), and the median follow-up was 5.2 years (IQR 2.2-10.0 years). As for treatment side effects and physical limitations, the scores of the CT+RPLND group were significantly higher than those of the WW group, especially within one year after treatment. In addition, TC survivors in the CT+RPLND group reported high impairment related to job and education problems and future perspective less than 5 years after treatment. Even TC survivors in the WW group were anxious about job and education issues within one year after treatment.

Conclusion: TC survivors were anxious about not only cancer recurrence, but also their jobs and education. TC patients should be given appropriate information on QOL after treatment for TC to attenuate post-treatment anxiety and improve their health-related QOL.
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http://dx.doi.org/10.1016/j.urology.2021.02.039DOI Listing
March 2021

Examination of pelvic floor muscle elasticity in patients with interstitial cystitis/bladder pain syndrome using real-time tissue elastography.

Int Urogynecol J 2021 Mar 19. Epub 2021 Mar 19.

Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.

Introduction And Hypothesis: The aim was to compare pelvic floor muscle (PFM) elasticity between interstitial cystitis/bladder pain syndrome (IC/BPS) patients and healthy women using real-time tissue elastography.

Methods: The subjects were 17 IC/BPS female patients (IC/BPS group; age 34-84 years), 10 healthy middle-aged women (middle-aged group; 50-80 years), and 17 healthy young adult women (young group; 23-37 years). The target sites of elastography were the striated urethral sphincter (SUS) and adipose tissue as the reference site; muscle elasticity was calculated as the strain ratio (SR) of the SUS to the reference site. Evaluations were performed at rest and during PFM contraction. The IC/BPS group completed lower urinary tract symptom and pain questionnaires. SUS SR was compared among the three groups. SUS SR at rest and during PFM contraction was compared among the three groups with the t-test and the Wilcoxon test. Associations between questionnaire results and SUS SR were evaluated by correlation analysis.

Results: There was no significant difference in age between the IC/BPS and middle-aged groups, but the young group was significantly younger than the other groups (p < 0.001). SUS SR at rest was significantly higher in the IC/BPS group than in the middle-aged (p = 0.014) and young groups (p = 0.002). Furthermore, in the IC/BPS group, there was no significant difference in SUS SR between at rest and during PFM contraction. SUS SR was not significantly correlated with questionnaire results for lower urinary tract symptoms.

Conclusions: SUS SR at rest was significantly higher in the IC/BPS group than in the young and middle-aged groups.
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http://dx.doi.org/10.1007/s00192-021-04761-7DOI Listing
March 2021

External validation of the albumin, C-reactive protein and lactate dehydrogenase model in patients with metastatic renal cell carcinoma receiving second-line axitinib therapy in a Japanese multi-center cohort.

Jpn J Clin Oncol 2021 Apr;51(5):810-818

Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Purpose: To externally validate the utility of the albumin, C-reactive protein and lactate dehydrogenase model to predict the overall survival of previously treated metastatic renal cell carcinoma patients.

Patients And Methods: The ability of the albumin, C-reactive protein and lactate dehydrogenase model to predict overall survival was validated and compared with those of other prognostication models using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib therapy at 36 hospitals belonging to the Japan Urologic Oncology Group.

Results: The following factors in this cohort were independently associated with poor overall survival in a multivariate analysis: a low Karnofsky performance status, <1 year from diagnosis to targeted therapy, a high neutrophil count, and low albumin, elevated C-reactive protein, and elevated lactate dehydrogenase, and the Japan Urologic Oncology Group model was newly developed based on the presence/absence of these independent factors. In this cohort, 151 (35.9%), 125 (27.7%) and 145 (34.4%) patients were classified into the favorable, intermediate and poor risk groups, respectively, according to the albumin, C-reactive protein and lactate dehydrogenase model; however, the proportions of patients in the intermediate risk group stratified by the Japan Urologic Oncology Group, Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models were >50%. The superiority of the albumin, C-reactive protein and lactate dehydrogenase model to the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models, but not the Japan Urologic Oncology Group model, was demonstrated by multiple statistical analyses.

Conclusions: The utility of the albumin, C-reactive protein and lactate dehydrogenase model as a simple and objective prognostication tool was successfully validated using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib.
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http://dx.doi.org/10.1093/jjco/hyaa264DOI Listing
April 2021

New year's greetings.

Authors:
Nobuo Shinohara

Int J Urol 2021 01;28(1)

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http://dx.doi.org/10.1111/iju.14479DOI Listing
January 2021

Girls and renal scarring as risk factors for febrile urinary tract infection after stopping antibiotic prophylaxis in children with vesicoureteral reflux.

World J Urol 2021 Jul 3;39(7):2587-2595. Epub 2021 Jan 3.

Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Purpose: To clarify the incidence of and risk factors for febrile urinary tract infection in children with persistent vesicoureteral reflux (VUR) after the discontinuation of continuous antibiotic prophylaxis (CAP), retrospective chart review was performed.

Patients And Methods: Among children with primary VUR at 10 years of age or younger at presentation, those who had persistent VUR despite conservative management with CAP and who were subsequently followed after discontinuation of CAP were included. Kaplan-Meier curve and Cox's proportional hazard regression model were used for evaluation of the incidence of and risk factors for febrile urinary tract infection (fUTI) after stopping CAP.

Results: Among 144 children (99 boys and 45 girls), fUTI developed in 34. The 5-year fUTI-free rate after discontinuation of CAP was 69.4%. On multivariate analyses, girls (p = 0.008) and abnormalities on nuclear renal scans (p = 0.0019), especially focal defect (p = 0.0471), were significant factors for fUTI. Although the fUTI-free rate was not different between children who had no or 1 risk factor, it was significantly lower in children with 2 risk factors than in those with no or 1 risk factor.

Conclusions: The present study revealed that girls and abnormal renal scan, especially focal defect, are risk factors for fUTI. Active surveillance without CAP for persistent VUR seems to be a safe option for children with no or 1 risk factor. Prophylactic surgery or careful conservative follow-up may be an option for girls with abnormal renal scan results if VUR persists under CAP.
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http://dx.doi.org/10.1007/s00345-020-03524-1DOI Listing
July 2021

Are sham-operated mice a valid comparator in studies using a bladder outlet obstruction model? A pitfall reveals a meaningful insight.

Int J Urol 2021 03 12;28(3):346-352. Epub 2020 Dec 12.

Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Objective: To evaluate voiding behavior characteristics in intact and sham mice, and to examine whether intact mice show changes in "normal" micturition with aging.

Methods: A total of 72 8-week-old mice were divided into two groups - intact and sham - and the latter group was subjected to a sham of partial bladder outlet obstruction surgery. Urination frequency was evaluated (through metabolic cages) at 1, 2, 3, 6 and 12 months after the surgery (or at the equivalent time points for the intact mice). To address possible mechanisms for aging and surgical effects on urinary behavior, quantitative real-time polymerase chain reaction assays were carried out. Primary data were evaluated using scatter plots and descriptive statistics.

Results: In sham mice, urination frequency showed strong variation at the earlier post-surgical time points (especially at 1 month), with variation decreasing with time. Quantitative real-time polymerase chain reaction showed that the serotonin 2C receptor-encoding mRNA accumulated to >28-fold higher levels at 24 months compared with 3 months in intact mice. A major limitation of the quantitative real-time polymerase chain reaction experiments was that we did not separate whole bladder into muscle and mucosa.

Conclusions: Although a sham operation is typically used in partial bladder outlet obstruction experiments to provide control animals, the sham group might itself show increased variation in micturition frequency at early times after surgery, compared with intact animals.
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http://dx.doi.org/10.1111/iju.14460DOI Listing
March 2021

Reliability and validity of pelvic floor muscle strength assessment using the MizCure perineometer.

BMC Womens Health 2020 11 19;20(1):257. Epub 2020 Nov 19.

Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7; Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

Background: The purpose of this study was to clarify the reliability and validity of pelvic floor muscle (PFM) strength assessment using the MizCure perineometer in healthy women.

Methods: Twenty healthy women (age 20-45 years) participated in this study. The vaginal pressure measured using the MizCure and validated Peritron perineometers were repeated during PFM contraction in the supine and standing positions. All women were evaluated twice by examiners 1 and 2. Following the measurements in the first session (Test 1), they were repeated after an interval of between 2 and 6 weeks (Test 2). Within- and between-session intra- and inter-rater reliabilities in vaginal pressure were analyzed using intraclass correlation coefficients (ICC) (1, 1) and (2, 1), respectively. Validity was assessed by Pearson's product-moment correlation coefficient and Spearman's rank correlation analysis.

Results: Within-session intra-rater reliabilities for both examiners 1 and 2 for all vaginal pressures in Tests 1 and 2 were 0.90-0.96 for both perineometers. Between-session intra-rater reliability for the MizCure was 0.72-0.79 for both positions for examiner 1, and 0.63 in the supine position and 0.80 in the standing position for examiner 2. Inter-rater reliability for Test 1 was 0.91 in the supine position and 0.87 in the standing position for the MizCure. The vaginal pressures using the MizCure and Peritron were significantly associated with the supine position (r = 0.68, P < .001) and the standing position (r = 0.82, P < .001).

Conclusion: MizCure perineometer is a validated tool to measure PFM strength in both supine and standing positions in healthy nulliparous women.
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http://dx.doi.org/10.1186/s12905-020-01127-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678071PMC
November 2020

Validation study of the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 for patients with testicular cancer.

Int J Urol 2021 Feb 10;28(2):176-182. Epub 2020 Nov 10.

Department of, Departments of, Urology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Objective: To validate the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 in Japanese-speaking testicular cancer survivors.

Methods: A total of 200 testicular cancer survivors were recruited at eight high-volume institutions in Japan. The participants completed the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and the International Index of Erectile Function 15 questionnaires. A total of 40 participants completed a retest of the questionnaires 2 weeks after the first response. The psychometric properties of the Japanese version including test-retest reliability, internal consistency and concurrent validity were evaluated.

Results: The mean age at response was 43 years (range 22-74 years), and the mean period after treatment was 77 months (range 0-416 months). The response rate for each item, except sexual function, was high, and the percentage of missing values was less than 3.5%. For test-retest reliability, seven of 12 scales met the criteria (intraclass correlation 0.70-0.86). For internal consistency, four of seven scales met the criteria (Cronbach's alpha 0.62-0.91). For concurrent validity, treatment side effects of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were related to some domains of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. The sex-related subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were moderately correlated with some International Index of Erectile Function 15 domains.

Conclusions: The psychometric properties of the Japanese version are equivalent to the properties of the original European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26. The Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 questionnaire is a useful tool to assess the health-related quality of life of testicular cancer patients.
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http://dx.doi.org/10.1111/iju.14422DOI Listing
February 2021

Femoral nerve palsy following kidney transplantation: A case report and review of the literature.

IJU Case Rep 2020 Nov 29;3(6):248-251. Epub 2020 Jul 29.

Department of Urology Hokkaido University Hospital Sapporo Japan.

Introduction: Femoral nerve palsy is a rare but serious complication of kidney transplantation. We report a case of femoral nerve palsy following kidney transplantation and conduct a review of the literature on this complication.

Case Presentation: A 35-year-old woman with end-stage kidney disease, underwent kidney transplantation in the right iliac fossa. The day after the transplantation, she could not straighten her right leg. Physical examination revealed a paresis of her right quadriceps muscle. The patient's sensation of her right thigh was also impaired. We diagnosed her with femoral nerve palsy caused by inappropriate compression from a self-retaining retractor. Rehabilitation was started immediately. The patient's motor weakness gradually improved, and the patient became able to walk independently 4 weeks later. However, the patient's neuropathic pain sustained 6 months after her kidney transplantation.

Conclusion: The improper use of self-retaining retractors can lead to femoral nerve palsy in patients undergoing kidney transplantation.
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http://dx.doi.org/10.1002/iju5.12207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609172PMC
November 2020

Difficulty in differential diagnosis for renal cancer with microscopic papillary architecture: overlapped pathological features among papillary renal cell carcinoma (RCC), mutinous tubular and spindle cell carcinoma, and unclassified RCC. Lessons from a Japanese multicenter study.

Jpn J Clin Oncol 2020 Oct;50(11):1313-1320

Department of Urology, National Defense Medical College, Saitama, Japan.

Objectives: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC.

Methods: We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features.

Results: All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3 years.

Conclusion: Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs.
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http://dx.doi.org/10.1093/jjco/hyaa114DOI Listing
October 2020

Effects of Repeated I-Iodobenzylguanidine Radiotherapy on Tumor Size and Tumor Metabolic Activity in Patients with Metastatic Neuroendocrine Tumors.

J Nucl Med 2021 05 16;62(5):685-694. Epub 2020 Oct 16.

Department of Diagnostic Radiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

I-iodobenzylguanidine (I-MIBG) radiotherapy has shown some survival benefits in metastatic neuroendocrine tumors (NETs). European Association of Nuclear Medicine clinical guidelines for I-MIBG radiotherapy suggest a repeated treatment protocol, although none currently exists. The existing single-high-dose I-MIBG radiotherapy (444 MBq/kg) has been shown to have some benefits for patients with metastatic NETs. However, this protocol increases adverse effects and requires alternative therapeutic approaches. Therefore, the aim of this study was to evaluate the effects of repeated I-MIBG therapy on tumor size and tumor metabolic response in patients with metastatic NETs. Eleven patients with metastatic NETs (aged 49.2 ± 16.3 y) prospectively received repeated 5,550-MBq doses of I-MIBG therapy at 6-mo intervals. In total, 31 treatments were performed. The mean number of treatments was 2.8 ± 0.4, and the cumulative I-MIBG dose was 15,640.9 ± 2,245.1 MBq (286.01 MBq/kg). Tumor response was observed by CT and F-FDG PET or by F-FDG PET/CT before and 3-6 mo after the final I-MIBG treatment. On the basis of the CT findings with RECIST, 3 patients showed a partial response and 6 patients showed stable disease. The remaining 2 patients showed progressive disease. Although there were 2 progressive-disease patients, analysis of all patients showed no increase in summed length diameter (median, 228.7 mm [interquartile range (IQR), 37.0-336.0 mm] to 171.0 mm [IQR, 38.0-270.0 mm]; = 0.563). In tumor region-based analysis with partial-response and stable-disease patients ( 9), I-MIBG therapy significantly reduced tumor diameter (79 lesions; median, 16 mm [IQR, 12-22 mm] to 11 mm [IQR, 6-16 mm]; < 0.001). Among 5 patients with hypertension, there was a strong trend toward systolic blood pressure reduction ( 0.058), and diastolic blood pressure was significantly reduced ( 0.006). Eighty-two percent of metastatic NET patients effectively achieved inhibition of disease progression, with reduced tumor size and reduced metabolic activity, through repeated I-MIBG therapy. Therefore, this relatively short-term repeated I-MIBG treatment may have potential as one option in the therapeutic protocol for metastatic NETs. Larger prospective studies with control groups are warranted.
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http://dx.doi.org/10.2967/jnumed.120.250803DOI Listing
May 2021

Long-term administration of alpha-1 blocker can reverse the micturition pattern in a bladder outlet obstruction murine model.

Int J Urol 2020 12 27;27(12):1150-1156. Epub 2020 Sep 27.

Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Objective: To investigate the effect of chronic administration of an alpha-1 blocker on micturition patterns in long-term partial bladder outlet obstruction.

Methods: Mice were divided into three groups: a normal group, in which animals were fed a standard diet; a partial bladder outlet obstruction group, in which the proximal urethra was tied and animals were fed a standard diet; and a partial bladder outlet obstruction + naftopidil group, in which the proximal urethra was tied and animals were fed a standard diet containing naftopidil. Micturition behavior was evaluated in all groups for 6 months after partial bladder outlet obstruction surgery. The parameters evaluated included voided volume, time per void, urination frequency and total urine volume. Quantitative assessment of gene expression was also carried out.

Results: Total urine volume, as well as total and average voided volume during night, was significantly decreased in partial bladder outlet obstruction + naftopidil mice compared with partial bladder outlet obstruction animals. The levels of transcripts encoding 5-hydroxytryptamine 2A and tissue inhibitor of metalloproteinase 2 were significantly decreased in the partial bladder outlet obstruction + naftopidil group compared with the partial bladder outlet obstruction group.

Conclusions: Long-term administration of an alpha-1 blocker seems to reverse the disturbance of the micturition pattern caused by partial bladder outlet obstruction. Mechanistically, this effect might be mediated by changes in the expression of a serotonin receptor and/or in the activity of the fibrogenesis pathway.
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http://dx.doi.org/10.1111/iju.14377DOI Listing
December 2020

Motion analysis for better understanding of psychomotor skills in laparoscopy: objective assessment-based simulation training using animal organs.

Surg Endosc 2021 Aug 9;35(8):4399-4416. Epub 2020 Sep 9.

Department of Urology, Hokkaido University Graduate School of Medicine, North-15, West-7, North Ward, Sapporo, 060-8638, Japan.

Background: Our aim was to characterize the motions of multiple laparoscopic surgical instruments among participants with different levels of surgical experience in a series of wet-lab training drills, in which participants need to perform a range of surgical procedures including grasping tissue, tissue traction and dissection, applying a Hem-o-lok clip, and suturing/knotting, and digitize the level of surgical competency.

Methods: Participants performed tissue dissection around the aorta, dividing encountered vessels after applying a Hem-o-lok (Task 1), and renal parenchymal closure (Task 2: suturing, Task 3: suturing and knot-tying), using swine cadaveric organs placed in a box trainer under a motion capture (Mocap) system. Motion-related metrics were compared according to participants' level of surgical experience (experts: 50 ≤ laparoscopic surgeries, intermediates: 10-49, novices: 0-9), using the Kruskal-Wallis test, and significant metrics were subjected to principal component analysis (PCA).

Results: A total of 15 experts, 12 intermediates, and 18 novices participated in the training. In Task 1, a shorter path length and faster velocity/acceleration/jerk were observed using both scissors and a Hem-o-lok applier in the experts, and Hem-o-lok-related metrics markedly contributed to the 1st principal component on PCA analysis, followed by scissors-related metrics. Higher-level skills including a shorter path length and faster velocity were observed in both hands of the experts also in tasks 2 and 3. Sub-analysis showed that, in experts with 100 ≤  cases, scissors moved more frequently in the "close zone (0  ≤ to < 2.0 cm from aorta)" than those with 50-99 cases.

Conclusion: Our novel Mocap system recognized significant differences in several metrics in multiple instruments according to the level of surgical experience. "Applying a Hem-o-lok clip on a pedicle" strongly reflected the level of surgical experience, and zone-metrics may be a promising tool to assess surgical expertise. Our next challenge is to give completely objective feedback to trainees on-site in the wet-lab.
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http://dx.doi.org/10.1007/s00464-020-07940-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263434PMC
August 2021

Animal Model for Lower Urinary Tract Dysfunction in Parkinson's Disease.

Int J Mol Sci 2020 Sep 7;21(18). Epub 2020 Sep 7.

Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8648, Japan.

Although Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and subsequent motor symptoms, various non-motor symptoms often precede these other symptoms. While motor symptoms are certainly burdensome, a wide range of non-motor symptoms have emerged as the key determinant of the quality of life in PD patients. The prevalence of lower urinary tract symptoms differs according to the study, with ranges between 27% and 63.9%. These can be influenced by the stage of disease, the presence of lower urinary tract-related comorbidities, and parallels with other manifestations of autonomic dysfunction. Animal models can provide a platform for investigating the mechanisms of PD-related dysfunction and for the assessment of novel treatment strategies. Animal research efforts have been primarily focused on PD motor signs and symptoms. However, the etiology of lower urinary tract dysfunction in PD has yet to be definitively clarified. Several animal PD models are available, each of which has a different effect on the autonomic nervous system. In this article, we review the various lower urinary tract dysfunction animal PD models. We additionally discuss techniques for determining the appropriate model for evaluating the development of lower urinary tract dysfunction treatments.
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http://dx.doi.org/10.3390/ijms21186520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554934PMC
September 2020

Health-related quality of life in Japanese patients with bladder cancer measured by a newly developed Japanese version of the Bladder Cancer Index.

Int J Clin Oncol 2020 Dec 24;25(12):2090-2098. Epub 2020 Aug 24.

Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Introduction: We validated a Japanese version of the Bladder Cancer Index (BCI) as a tool for measuring health-related quality of life (HRQOL) in bladder cancer patients treated with various surgical procedures.

Methods: The reliability and validity of the Japanese BCI were examined in 397 Japanese patients with bladder cancer via cross-sectional analysis. The patients simultaneously completed the Short Form (SF)-12, EQ-5D, and the Functional Assessment of Cancer Therapy-General and Bladder (FACT-G and FACT-BL). The differences in BCI subscales among various treatment groups were analyzed.

Results: This study involved 397 patients (301 males and 96 females), with a mean age of 70 years and a median disease duration of 29 months (IQR: 12-66 months). Of these patients, 221 underwent transurethral resection of a bladder tumor, and 176 patients underwent radical cystectomy (ileal conduit: 101 patients, ileal neobladder: 49, and ureterostomy: 26). Cronbach's alpha coefficient was ≥ 0.78 for all subscales, except the bowel bother subscale. Despite moderate correlations being detected between the function and bother score in urinary and bowel domains, the sexual function score was inversely correlated with the sexual bother score (r = - 0.19). A missing value percentage of > 15% was associated with old age (p < 0.05). The mean domain scores differed significantly among distinct clinically relevant treatment groups.

Conclusions: Although revisions are needed to make it easier for elderly patients to comprehend, we confirmed the reliability and validity of the Japanese BCI. The Japanese BCI could be used for cross-cultural assessments of HRQOL in bladder cancer patients.
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http://dx.doi.org/10.1007/s10147-020-01770-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677272PMC
December 2020

The impact of complications after initial prostate biopsy on repeat protocol biopsy acceptance rate. Results from the Prostate Cancer Research International: Active Surveillance JAPAN study.

Int J Clin Oncol 2020 Dec 8;25(12):2107-2114. Epub 2020 Aug 8.

Department of Urology, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.

Background: Patients with favorable-risk prostate cancer on active surveillance (AS) are strictly followed for safer execution. Repeat protocol biopsy is essential for evaluating cancer aggressiveness. However, the acceptance rate of repeat biopsy is not high enough because of the burdens of biopsy. We assessed the impact of complications after the initial biopsy on repeat protocol biopsy at 1 year using data from the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study.

Methods: We performed a retrospective analysis using a prospective cohort in the PRIAS-JAPAN study. Patients with favorable-risk prostate cancer (n = 856) who consented to participate in the PRIAS-JAPAN study from 2010 to 2018 were enrolled. Follow-up evaluations included regular prostate-specific antigen, digital rectal examination and biopsy. Rates of complications after biopsies and repeat protocol biopsy non-acceptance rate at 1 year were reported. Logistic regression analysis explored the association between the complications after the initial biopsy and repeat protocol biopsy non-acceptance.

Results: Altogether, 759 patients (88.7%) actually proceeded to protocol at 1 year. Repeat protocol biopsy non-acceptance rate at 1 year was 14.9%. Regarding complications after the initial biopsy, hematuria (p = 0.028) and pain (p < 0.001) rates were significantly higher in the repeat biopsy non-acceptance group, but infection (p = 0.056) and hematospermia (p = 0.337) rates were not different. On multivariate logistic regression analysis, pain was a significant predictor for repeat protocol biopsy non-acceptance (odds ratio 4.68, 95% confidence interval 1.864-11.75; p = 0.001).

Conclusions: Pain at the initial biopsy negatively impacts patients' compliance with further protocol biopsies during AS.
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http://dx.doi.org/10.1007/s10147-020-01761-3DOI Listing
December 2020

Development and validation of a porcine organ model for training in essential laparoscopic surgical skills.

Int J Urol 2020 10 3;27(10):929-938. Epub 2020 Aug 3.

Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.

Objectives: To develop a wet laboratory training model for learning core laparoscopic surgical skills and evaluating learners' competency level outside the operating room.

Methods: Participants completed three tasks (task 1: tissue dissection around the aorta; task 2: tissue dissection and division of the renal artery; task 3: renal parenchymal closure). Each performance was video recorded and subsequently evaluated by two experts, according to the Global Operative Assessment of Laparoscopic Skills and task-specific metrics that we developed (Assessment Sheet of Laparoscopic Skills in Wet Lab score). Mean scores were used for analyses. The subjective mental workload was also assessed (NASA Task Load Index).

Results: The 54 participants included 32 urologists, eight young trainees and 14 medical students. A total of 13 participants were categorized as experts (≥50 laparoscopic surgeries), eight as intermediates (10-49) and 33 as novices (0-9). There were significant differences in the Global Operative Assessment of Laparoscopic Skills and Assessment Sheet of Laparoscopic Skills in Wet Lab scores among the three groups in all three tasks. Higher NASA Task Load Index scores were observed in novices, and there were significant differences in tasks 1 (Kruskal-Wallis test, P = 0.0004) and 2 (P = 0.0002), and marginal differences in task 3 (P = 0.0745) among the three groups.

Conclusions: Our training model has good construct validity, and differences in the NASA Task Load Index score reflect previous laparoscopic surgical experiences. Our findings show the ability to assess both laparoscopic surgical skills and mental workloads, which could help educators comprehend trainees' level outside the operating room. Given the decreasing opportunity to carry out pure laparoscopic surgeries because of the dissemination of robotic surgery, especially in urology, our model can offer practical training opportunities.
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http://dx.doi.org/10.1111/iju.14315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589398PMC
October 2020

Bladder outlet obstruction disrupts circadian bladder function in mice.

Sci Rep 2020 07 14;10(1):11578. Epub 2020 Jul 14.

Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

The circadian clock programs daily rhythms and coordinates multiple behavioural processes, including micturition. Partial bladder outlet obstruction (pBOO) in mice produces hyperactive voiding. However, long-term effects of pBOO on bladder function have not been clarified. In this study, we investigated micturition under conditions of impaired circadian bladder function by inducing long-term pBOO by tying the proximal urethra. Micturition behavior was evaluated at 1, 3, 6 and 12 months after surgery. We used automated voided stain on paper method for a precise micturition recording for mice. And quantitative assessment of gene expression was performed at 24 months after pBOO surgery using qRT-PCR procedure. The micturition frequencies in the pBOO group were significantly decreased at 3, 6, and 12 months compared to those at 1 month after operation in the same group (p < 0.05). Body weight of pBOO mice was significantly increased compared to sham operated mice at 12 months. The expression level of mRNA was exhibited a 3.4-fold nominal increased for a 5-HT2B receptor in the pBOO group compared to the sham group. The current study found that long-term pBOO led to disruption of the circadian bladder function (the day/night cycle) in mice, similar to those observed in human as nocturia. This disruption is possible involvement of the gain of body weight and/or serotonergic alteration after pBOO.
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http://dx.doi.org/10.1038/s41598-020-68499-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360733PMC
July 2020
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