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Abstract Although the mRNA SARS-CoV-2 vaccine has improved the mortality rate in the general population, its efficacy against rapidly mutating virus strains, especially in kidney transplant recipients, remains unclear. We examined the anti-SARS-CoV-2 spike protein IgG antibody and neutralizing antibody titers and cellular immunity against B.1.1, BA.1, and BA.5 antigens in 73 uninfected kidney recipients and 16 uninfected healthy controls who received three doses of an mRNA SARS-CoV-2 vaccine. The IgG antibody titers were significantly lower in recipients than in healthy controls. Similarly, neutralizing antibody titers against three viral variants were significantly lower in recipients. When the virus was mutated, the neutralizing antibody titers decreased significantly in both groups. In cellular immunity analysis, the number of spike-specific CD8 + non-naïve T cells against three variants significantly decreased in recipients. Conversely, the frequency of spike-specific Th2 CD4 + T-cells in recipients was higher than that in healthy controls. Nineteen recipients and six healthy controls also received a bivalent omicron-containing booster vaccine, leading to increase IgG and neutralizing antibody titers in both groups. After that, eleven recipients and five healthy controls received XBB.1.5 monovalent vaccines, increasing the neutralizing antibody titers against not only XBB.1.5, but also EG.5.1 and BA.2.86 antigens in kidney recipients. Although kidney recipients did not gain sufficient immunity against Omicron BA.5 with the third dose of vaccine, humoral response against mutant SARS-CoV-2 lineages significantly increased after bivalent Omicron-containing booster vaccine and the XBB.1.5 monovalent vaccine. Therefore, it is important for kidney recipients to continue to administer updated vaccines.

Abstract New technologies such as laparoscopic and robotic surgery are spreading, and there is a demand for physicians to keep up with novel methods. In contrast to the recent focus on healthcare professional burnout, the mental and physical costs during surgery are not well-understood. We aimed to quantify surgeons’ workloads in daily urological surgical practice and clarify potential background factors associated with such workloads. Urologists in Hokkaido, Japan, were invited to this study. Between December 2020 and December 2021, participants repeatedly reported workloads, which were assessed using the National Aeronautics and Space Administration-Task Load Index (NASA-TLX), after each surgery in conjunction with participants’ names, patients’ backgrounds, their roles (independent operator, operator under supervision, instructor, and 1st or 2nd assistant), and surgical outcomes, via SurveyMonkey®. Because of the heterogeneity among individuals, a linear mixed-effects model was utilized to analyze factors associated with NASA-TLX, calculating the parameter estimates (PE) of regression coefficients for each factor and their 95% confidence interval (CI). Sixty-five urologists (5 women) joined the study, and 2169 data were collected within 7 days after surgeries. A linear mixed-effects model revealed that female surgeons (PE + 15.56, 95% CI 2.36–28.77), urgent/emergency surgery (PE + 6.65, 95% CI 4.59–8.70), intraoperative complications (PE + 9.26, 95% CI 6.76–11.76), and near-miss incidents (PE + 3.81, 95% CI 2.27–5.36) were associated with higher workloads. Regarding the surgeons’ role, operator under supervision (PE + 12.46, 95% CI 9.86–15.06) showed the highest workloads. Surgeons’ workloads decreased as the number of previous cases of the same procedure increased. Surgeons’ workloads were associated with various factors. Given that the highest workloads were for operators under supervision, instructors should be aware of trainees’ high workloads and devise appropriate instructional interventions.

Abstract We designed this multi-center prospective study with the following objectives: (1) the cross-sectional validation of extracellular vesicles (EV) mRNA markers to detect urothelial bladder cancer (UBC) before transurethral resection of bladder cancer (TURBT), and (2) the longitudinal validation of EV mRNA markers to monitor non-muscle invasive bladder cancer (NMIBC) recurrence after TURBT. EV mRNA markers evaluated in this study were KRT17, GPRC5A, and SLC2A1 in addition to two additional markers from literatures, MDK and CXCR2, and measured by quantitative RT-PCR with normalization by a reference gene (ALDOB). Diagnostic performances of EV mRNA markers were compared to conventional markers. Regarding the first objective, we confirmed that EV mRNA biomarkers in urine were higher in UBC patients, particularly those with higher stage/grade tumors, than in those without UBC (n = 278 in total) and the diagnostic performance of EV mRNA MDK and KRT17 outperformed conventional biomarkers with AUC 0.760 and 0.730, respectively. Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p

Abstract Objective This study investigated morphological changes in the composition of the pelvic floor muscles, degree of atrophy, and urethral function in a rat of simulated birth trauma induced by vaginal distension (VD) model. Methods Female Sprague–Dawley rats were classified into four groups: a sham group, and 1, 2, and 4 weeks post-VD (1 W, 2 W, and 4 W, respectively) groups. We measured the amplitude of urethral response to electrical stimulation (A-URE) to evaluate urethral function. After measuring the muscle wet weight of the pubococcygeus (Pcm) and iliococcygeus (Icm) muscles, histochemical staining was used to classify muscle fibers into Types I, IIa, and IIb, and the occupancy and cross-sectional area of each muscle fiber were determined. Results There were 24 Sprague–Dawley rats used. A-URE was significantly lower in the 1 W group versus the other groups. Muscle wet weight was significantly lower in the VD groups versus the sham group for Pcm. The cross-sectional area of Type I Pcm and Icm was significantly lower in the VD groups versus the sham group. Type I muscle fiber composition in Pcm was significantly lower in the VD groups versus the sham groupand lowest in the 2 W group. Type I muscle fiber composition in Icm was significantly lower in the 2 and 4 W groups versus the sham group. Conclusion Muscle atrophy and changes in muscle composition in the pelvic floor muscles were observed even after improvements in urethral function. These results may provide insight into the pathogenesis of stress urinary incontinence after VD.

Abstract Objective To achieve patient‐centricity in metastatic renal cell carcinoma (mRCC) treatment, it is essential to clarify the differences in perspectives between patients and physicians. This cross‐sectional analysis of a web survey aimed to clarify the differences in expectations and concerns between mRCC patients and physicians regarding systemic mRCC therapy in Japan. Methods Surveys from 83 patients and 165 physicians were analyzed. Results The top three most significant differences in expectations of systemic therapy between patients and physicians (patient‐based physician value) were “Chance of achieving treatment‐free status” (−30.1%, p

This study developed and validated a surgical instrument motion measurement system for skill evaluation during practical laparoscopic surgery training. Owing to the various advantages of laparoscopic surgery including minimal invasiveness, this technique has been widely used. However, expert surgeons have insufficient time for providing training to beginners due to the shortage of surgeons and limited working hours. Skill transfer efficiency has to be improved for which there is an urgent need to develop objective surgical skill evaluation methods. Therefore, a simple motion capture-based surgical instrument motion measurement system that could be easily installed in an operating room for skill assessment during practical surgical training was developed. The tip positions and orientations of the instruments were calculated based on the marker positions attached to the root of the instrument. Because the patterns of these markers are individual, this system can track multiple instruments simultaneously and detect exchanges. However due to the many obstacles in the operating room, the measurement data included noise and outliers. In this study, the effect of this decrease in measurement accuracy on feature calculation was determined. Accuracy verification experiments were conducted during wet-lab training to demonstrate the capability of this system to measure the motion of surgical instruments with practical accuracy. A surgical training experiment on a cadaver was conducted, and the motions of six surgical instruments were measured in 36 cases of laparoscopic radical nephrectomy. Outlier removal and smoothing methods were also developed and applied to remove the noise and outliers in the obtained data. The questionnaire survey conducted during the experiment confirmed that the measurement system did not interfere with the surgical operation. Thus, the proposed system was capable of making reliable measurements with minimal impact on surgery. The system will facilitate surgical education by enabling the evaluation of skill transfer of surgical skills.

Information on the financial toxicity experienced by Japanese patients with metastatic renal cell carcinoma (mRCC) is lacking, even though Japan has its own unique public health insurance system. Thus, a web-based survey was conducted to evaluate the financial toxicity experienced by Japanese mRCC patients using the COmprehensive Score for financial Toxicity (COST) tool. This study enrolled Japanese patients who underwent, or were undergoing, systemic therapy for mRCC. The outcomes evaluated were the distribution of COST scores, the correlation between COST and quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) scale, and demographic factors associated with financial toxicity. The median (range) COST score was 19.0 (3.0–36.0). The Pearson correlation coefficient for COST and FACT-G total scores was 0.40. Univariate analysis revealed that not having private health insurance and lower household income per year were significantly associated with lower COST scores. Multivariate analyses showed that age < 65 years and not having private health insurance were significantly associated with lower COST scores. This study revealed that Japanese mRCC patients experience adverse financial impacts even under the universal health insurance coverage system available in Japan, and financial toxicity negatively affects their QOL.

Introduction Cabozantinib monotherapy is an option for treatment of advanced renal cell carcinoma (RCC). However, cabozantinib dose modification and discontinuation due to symptomatic adverse events (AEs) remains a challenge. The use of patient-reported outcomes (PROs) may help manage symptomatic AEs, which is reported to lead to improved quality of life (QOL), avoidance of drug discontinuation and better survival. This study aims to investigate the clinical benefits of PROs in patients with RCC receiving cabozantinib and the most appropriate medium for PRO monitoring (electronic [e]-PRO or paper-PRO).Methods and analysis This study is being conducted at about 35 sites in Japan. Patients aged ≥18 years with unresectable or metastatic RCC initiating treatment with cabozantinib monotherapy are eligible and will be randomised to: (1) e-PRO monitoring, (2) paper-PRO monitoring or (3) usual care without PRO monitoring. Recruitment began in December 2021 (target sample size, 105). Patients start treatment with cabozantinib 60 mg once daily, and in the PRO groups, will record daily medication intake, weight, temperature, blood pressure and AEs. Endpoints include the proportion of patients with a ≥5-point deterioration on the Functional Assessment of Cancer Therapy-Kidney Cancer Symptom Index (FKSI-19; primary endpoint), progression-free survival, QOL, dose adjustments, relative dose intensity, treatment-emergent AEs and frequency of interventions for AEs outside of the scheduled visits. Patient and physician opinions of the PRO monitoring systems and patient compliance with e-PRO/paper-PRO input are also being measured.Ethics and dissemination The study is being conducted in compliance with the Declaration of Helsinki, the International Council for Harmonisation guidelines for Good Clinical Practice and the Clinical Trials Act. Written informed consent is being obtained from all patients, and the protocol has been approved by the Hokkaido University Hospital Certified Review Board (approval number, CRB021-005). The results will be presented at conferences and submitted to a peer-reviewed journal.Trial registration number jRCTs011210055.

Abstract The Body Image Scale (BIS) is a 10-item tool that measures the body images of cancer patients. This study aims to validate the Japanese version of the BIS for bladder cancer patients. A multicenter cross-sectional survey was used to identify the participants, which included Japanese bladder cancer patients. The percentage of missing responses, internal consistency, and known-group validity were evaluated. The correlations between the BIS and two HRQOL instruments (the Bladder Cancer Index and the SF-12) were assessed to determine convergent validity. Among 397 patients, 221 patients were treated by transurethral resection of bladder tumor (TURBT) endoscopically, 49 patients underwent cystectomy with neobladder, and 127 patients underwent cystectomy involving stoma. The percentage of missing responses in the BIS ranged from 8.1 to 15.6%. Cronbach's α coefficient was 0.924. Higher BIS scores indicate negative body image, and the median BIS score for patients with native bladders after TURBT (0.5) was significantly lower than those of the patients with neobladder (4.0) and stoma formation (7.0), which indicated the discriminatory ability of the BIS. Each domain of the Bladder Cancer Index and the role summary score of the SF-12 correlated to the BIS scores, which confirmed the convergent validity. A range of BIS scores were identified among patients who reported similar physical summary scores and mental summary scores of the SF-12. This study confirmed the reliability and validity of the Japanese version of the BIS for bladder cancer patients.

Abstract Background Previous clinical trials have demonstrated the potential efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) in patients with cancer involving homologous recombination repair (HRR) gene-mutation. Moreover, HRR gene-mutated cancers are effectively treated with immune checkpoint inhibitors (ICIs) with the increase in tumor mutation burden. We have proposed to conduct a multicenter, single-arm phase II trial (IMAGENE trial) for evaluating the efficacy and safety of niraparib (PARPi) plus programmed cell death-1 inhibitor combination therapy in patients with HRR gene-mutated cancers who are refractory to ICIs therapy using a next generation sequencing-based circulating tumor DNA (ctDNA) and tumor tissue analysis. Methods Key eligibility criteria for this trial includes HRR gene-mutated tumor determined by any cancer gene tests; progression after previous ICI treatment; and Eastern Cooperative Oncology Group Performance Status ≤ 1. The primary endpoint is the confirmed objective response rate (ORR) in all patients. The secondary endpoints include the confirmed ORR in patients with HRR gene-mutation of ctDNA using the Caris Assure (CARIS, USA). The target sample size of the IMAGENE trial is 57 patients. Biomarker analyses will be performed in parallel using the Caris Assure, proteome analysis, and T cell repertoire analysis to reveal tumor immunosurveillance in peripheral blood. Expected outcome Our trial aims to confirm the clinical benefit of PARPi plus ICI combination therapy in ICI-resistant patients. Furthermore, through translational research, our trial will shed light on which patients would benefit from the targeted combination therapy for patients with HRR gene-mutated tumor even after the failure of ICIs. Trial registration The IMAGENE trial: jRCT, Clinical trial no.: jRCT2051210120, Registered date: November 9, 2021.

Abstract Introduction We report a case of laparoscopic adrenalectomy in a salvage setting after multiple chemotherapies for neuroendocrine carcinoma. Case presentation A 49‐year‐old man was diagnosed with unknown primary carcinoma with single brain metastasis, and right supraclavicular and mediastinal lymph node metastases. After stereotactic radiotherapy of the brain metastasis and systemic chemotherapy, lymphadanectomy was performed. The pathologic diagnosis was neuroendocrine carcinoma. At 11 months after surgery, computed tomography revealed right adrenal metastasis. Local radiotherapy initially resulted in complete remission. However, adrenal recurrence was noted 10 months later. Laparoscopic adrenalectomy was performed with curative intent. The patient is currently alive without recurrence at 20 months after the operation. Conclusion Adrenalectomy can become a treatment option if other metastases are well‐controlled with systemic therapy. Surgical elimination of oligometastases can offer long‐term disease control in selected patients as part of a multimodal approach.

A 62-year-old woman presented with a tumor in the right kidney. A right partial nephrectomy was performed, and the tumor was diagnosed as clear cell renal cell carcinoma (RCC) on histopathological examination. A right ovarian tumor was detected on follow-up computed tomography (CT) 5 years after partial nephrectomy and pathology proved RCC metastasis. RCC rarely metastasizes to the ovaries. There is limited information on the radiological features of ovarian metastasis in RCC. In this case report, we presented the CT and magnetic resonance images of ovarian metastasis of RCC. In addition, we also presented a literature review with special emphasis on the imaging features of ovarian metastasis of RCC.

Donor-specific antibodies (DSAs) are the main cause of graft loss over time. The direct pathway of alloantigen recognition is important in the pathogenesis of acute rejection. Recent studies have suggested that the direct pathway also contributes to the pathogenesis of chronic injury. Nevertheless, there are no reports on T-cell alloantigen response via the direct pathway in kidney recipients with DSAs. We analyzed the T-cell alloantigen response via the direct pathway in kidney recipients with DSAs (DSA+) or without DSAs (DSA−). A mixed lymphocyte reaction assay was implemented to assess the direct pathway response. DSA+ patients showed significantly higher CD8+ and CD4+ T cell responses to donor cells than DSA− patients. Furthermore, proliferating CD4+ T cells showed a marked increase in Th1 and Th17 responses in DSA+ patients than in DSA− patients. In a comparison between anti-donor and third-party responses, the anti-donor CD8+ and CD4+ T cell response was significantly lower than the anti-third-party response. In contrast, the donor-specific hyporesponsiveness was absent in DSA+ patients. Our study demonstrated that DSA+ recipients have a greater potential for developing immune responses against the donor tissues via the direct alloantigen recognition pathway. These data contribute to an understanding of DSAs pathogenicity during kidney transplantation.

Abstract Background It has been hypothesized that women with significant pelvic organ prolapse (POP), particularly of the anterior vaginal wall, may have voiding dysfunction (VD). Although the VD mechanism due to cystocele is not fully understood, different vaginal compartments have rarely been closely examined. This study attempted to further elucidate the correlation between POP and VD through a new subgroup classification using cystoscopy. Methods This study reviewed clinical records of 49 women who underwent cystocele repair. All patients were scheduled for laparoscopic sacrocolpopexy, preoperatively underwent uroflowmetry and postvoid residual urine volume (PVR) measurement, and completed pelvic floor function questionnaires. Bladder examination by cystoscopy was additionally performed using the lithotomy position with the Valsalva maneuver. Results Subjects were divided into four groups according to hernia orifice presence determined by cystoscopy, which included the trigone type, posterior wall type, trigone and urethra type, and trigone and posterior wall type. The posterior wall type had statistically higher PVR values versus the trigone and posterior wall type (P = 0.013). The posterior wall type had statistically lower values for average urine flow rate versus the urethra and trigone type (P = 0.020). There were no significant differences noted in the pelvic floor function questionnaires among the four groups. Conclusions A new bladder defect classification based upon hernia orifice location was associated with lower urinary tract function. Posterior wall hernia presence caused significant voiding function deterioration. This new subgroup classification, which can more clearly identify and indicate bladder function, is also comparable among patients.

Introduction Granulocyte colony‐stimulating factor‐producing upper urinary tract urothelial carcinoma is rare, with a poor prognosis. Advanced urothelial carcinoma is currently treated with immune checkpoint inhibitors, whose efficacy for granulocyte colony‐stimulating factor‐producing upper urinary tract urothelial carcinoma remains unclear. Case presentation A 66‐year‐old male diagnosed with clinical stage T3N1M0 urothelial carcinoma of the right ureter with giant hydronephrosis underwent right radical nephroureterectomy. Local recurrence, leukocytosis, and elevated serum granulocyte colony‐stimulating factor levels were observed approximately 3 months after surgery. Chemotherapy was started but failed to control the disease. Therefore, pembrolizumab was chosen as the second‐line treatment. After this treatment, the blood leukocyte count rapidly normalized, and a clinically favorable response was achieved. There was no recurrence 10 months after the beginning of pembrolizumab treatment, which is still ongoing. Conclusion Pembrolizumab may be a treatment option for advanced granulocyte colony‐stimulating factor‐producing upper urinary tract urothelial carcinoma.

Abstract Parkinson’s disease (PD) is a neurodegenerative condition caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. As activation of dopaminergic receptors is fundamentally involved in the micturition reflex in PD, the objective of this study was to determine the effect of a single dose of rotigotine ([−]2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin) on intercontraction interval (ICI) and voiding pressure (VP) in a rat model of PD. We used 27 female rats, PD was induced by injecting 6-hydroxydopamine (6-OHDA; 8 μg in 2 μL of 0.9% saline containing 0.3% ascorbic acid), and rotigotine was administrated at doses of 0.125, 0.25, or 0.5 mg/kg, either intravenous or subcutaneous injection. In rats with 6-OHDA-induced PD, intravenous injection of 0.25 or 0.5 mg/kg rotigotine led to a significantly lower ICI than after vehicle injection (p

Abstract Background To investigate the need for ureteral reimplantation for vesicoureteral reflux (VUR) during augmentation cystoplasty (AC) in the long term. Methods A total of 19 patients with a median age at surgery of 14 years (3–38 years) who underwent AC for neurogenic bladder with VUR between 1983 and 2016 were included in this study. The changes in VUR grade and urodynamic findings were retrospectively evaluated. We evaluated the renal function by periodic inspection of serum creatinine level and estimated glomerular filtration rate; eGFR. Results The median follow-up period from AC was 14.8 years (5.7–30 years). VUR was detected in 19 patients, involving 27 ureters. Reflux grade was V in 6, IV in 9, III in 5, II in 6, and I in 1. Ureteral reimplantation was not performed in 18 patients (26 ureters), whereas it was done for 1 patient (1 ureter) in the early era of our experience. Postoperative videourodynamics showed that the reflux was radiologically not verifiable in 23 ureters (85%), was downgraded in 3 ureters (11%), and was unchanged in 1 ureter (3%). There were no cases of deterioration of VUR. Conclusions Ureteral reimplantation is not necessary for VUR during augmentation cystoplasty.

Introduction We report a rare case of primary renal leiomyosarcoma with a tumor thrombus in the inferior vena cava. Case presentation A 54‐year‐old woman presented with right flank pain and abdominal distension. Physical examination findings were unremarkable. Abdominal computed tomography revealed a heterogeneously enhancing right solid renal mass with a thrombus in the renal vein extending into the inferior vena cava. Magnetic resonance imaging demonstrated a renal tumor with a thrombus about 4 cm below the hepatic vein. Chest computed tomography and bone scintigraphy were negative. The patient underwent right radical nephrectomy and vena cava thrombectomy. Histophathologic evaluation of the resected tumor confirmed the diagnosis of leiomyosarcoma. She underwent no adjuvant therapy. Seven months after surgery, the patient died following a 2‐month history of multiple pulmonary and hepatic metastases. Conclusion This report highlights the importance of considering the possibility of renal leiomyosarcoma invasion to the inferior vena cava, similar to renal cell carcinoma.

Prostate MRI scans for pre-biopsied patients are important. However, fewer radiologists are available for MRI diagnoses, which requires multi-sequential interpretations of multi-slice images. To reduce such a burden, artificial intelligence (AI)-based, computer-aided diagnosis is expected to be a critical technology. We present an AI-based method for pinpointing prostate cancer location and determining tumor morphology using multiparametric MRI. The study enrolled 15 patients who underwent radical prostatectomy between April 2008 and August 2017 at our institution. We labeled the cancer area on the peripheral zone on MR images, comparing MRI with histopathological mapping of radical prostatectomy specimens. Likelihood maps were drawn, and tumors were divided into morphologically distinct regions using the superpixel method. Likelihood maps consisted of pixels, which utilize the cancer likelihood value computed from the T2-weighted, apparent diffusion coefficient, and diffusion-weighted MRI-based texture features. Cancer location was determined based on the likelihood maps. We evaluated the diagnostic performance by the area under the receiver operating characteristic (ROC) curve according to the Chi-square test. The area under the ROC curve was 0.985. Sensitivity and specificity for our approach were 0.875 and 0.961 (p < 0.01), respectively. Our AI-based procedures were successfully applied to automated prostate cancer localization and shape estimation using multiparametric MRI.

Abstract Background Removal of anti-blood group antibodies is important for successful ABO-incompatible kidney transplantation (ABOi-KTx). Double-filtration plasmapheresis (DFPP) using albumin solution removes antibodies effectively. However, fibrinogen is largely removed resulting in hemostatic failure. Herein, we designed an altered combination of plasma membranes in DFPP (novel DFPP, nDFPP) to retain more fibrinogen while removing IgG, and assessed its efficacy and safety compared with conventional DFPP (cDFPP). Methods Consecutive ABOi-KTx recipients (from 2015 to 2018) were enrolled. For the first membrane, we used Cascadeflo EC-50W in nDFPP and Plasmaflo OP-08W in cDFPP, and Cascadeflo EC-20W as the second membrane in both modalities. Removal rates (RR) of IgG, IgM and fibrinogen per DFPP session, and adverse events were compared with historical control patients who underwent cDFPP before ABOi-KTx, between 2006 and 2015. Results nDFPP and cDFPP groups included 12 and 23 cases, respectively. nDFPP was inferior to cDFPP in RR of IgG and IgM. nDFPP was also inferior to cDFPP in the decline in anti-blood group IgG and IgM antibody titers. However, fibrinogen was more preserved in nDFPP compared with cDFPP, indicating that nDFPP has more selective removal properties (median RR of IgG, IgM, and fibrinogen: 62.1%, 15.7% and 37.6%, respectively, in nDFPP; and 74.5%, 85.0% and 76.6%, respectively, in cDFPP). In the comparison of hemostatic function among the patients who had arteriovenous fistula for hemodialysis, prolonged hemostasis (> 20 min) at the cannulation site was significantly less frequently observed in nDFPP group (1 in 9 cases, 9.1%) than in cDFPP group (all 18 cases, 10%, p

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.

Abstract 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

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.

BackgroundA positive flow-cytometry T cell crossmatch (FTXM) has important prognostic implications, even when the complement-dependent cytotoxicity crossmatch is negative. Recent studies have shown that ABO incompatibility is associated with positive FTXM, but the underlying mechanism remains poorly understood.CasesIn five ABO blood type O recipients of kidneys from wives with type B, FTXM was positive but complement-dependent cytotoxicity crossmatch was negative. Application of a solid-phase technique (LABScreen) revealed no case with antibodies to donor-specific human leukocyte antigen. After removal of type B antibodies from patient sera, FTXM was negative for all five patients. In one tested case, the eluate prepared from the donor’s T lymphocyte agglutinated only type B red blood cells, implying the existence of blood type B substances on donor T lymphocytes.DiscussionFalse-positive FTXM reflects blood type B substrates bound to T lymphocytes. Repeat FTXM after incubation with donor-type red blood cells (to adsorb anti-ABO antibodies) was negative. This phenomenon explains the discrepancy between FTXM and solid-phase bead assays. Demonstration of type B substances on donor T lymphocytes is necessary before absolute test validity is confirmed.ConclusionFalse-positive FTXM may be associated with type B antibodies bound to T lymphocytes when a blood type O recipient receives tissue from a type B donor. This phenomenon explains the false-positive FTXM observed in the setting of ABO-incompatible kidney transplantation.

BackgroundThe quality of transurethral resection of bladder tumor (TURBT) markedly varies among surgeons and may have a considerable impact on treatment outcomes. The importance of a surgical checklist for TURBT has been suggested in order to standardize the procedure and improve surgical and oncological outcomes. In the present study, we verified the usefulness of a checklist for managing patients with non-muscle-invasive bladder cancer (NMIBC).MethodsThis retrospective study included 201 NMIBC patients diagnosed with Ta, T1, or Tis between October 2011 and February 2021. After September 2016, TURBT was performed with a checklist. We analyzed the intravesical recurrence-free survival (RFS) rate and the presence or absence of the detrusor muscle in resected specimens before and after the introduction of the checklist. Survival rates were compared using the Log-rank test. A multivariate analysis with Cox proportional hazards modeling was performed to verify risk factors for intravesical recurrence.ResultsNinety-nine patients who underwent TURBT with the checklist (checklist group) were compared with 102 patients who underwent TURBT without the checklist (non-checklist group). When the analysis was narrowed down to 9 critical items, we observed a mean number of 9 documented items per operative report (98.0% completion) after implementation of the checklist. Two-year intravesical RFS rates in the checklist and non-checklist groups were 76.7 and 69.5%, respectively (p = 0.1059). The Cox proportional multivariate analysis showed that the rate of intravesical recurrence was slightly lower in the checklist group (hazard ratio 0.7376, 95% CI 0.4064-1.3388, P = 0.3170).ConclusionThe introduction of a checklist is recommended for the standardization of TURBT and increasing the quality of operative reporting, and it may also improve oncological outcomes.

The purpose of this study was to characterize the motion features of surgical devices associated with laparoscopic surgical competency and build an automatic skill-credential system in porcine cadaver organ simulation training. Participants performed tissue dissection around the aorta, dividing vascular pedicles after applying Hem-o-lok (tissue dissection task) and parenchymal closure of the kidney (suturing task). Movements of surgical devices were tracked by a motion capture (Mocap) system, and Mocap-metrics were compared according to the level of surgical experience (experts: ≥50 laparoscopic surgeries, intermediates: 10–49, novices: 0–9), using the Kruskal-Wallis test and principal component analysis (PCA). Three machine-learning algorithms: support vector machine (SVM), PCA-SVM, and gradient boosting decision tree (GBDT), were utilized for discrimination of the surgical experience level. The accuracy of each model was evaluated by nested and repeated k-fold cross-validation. A total of 32 experts, 18 intermediates, and 20 novices participated in the present study. PCA revealed that efficiency-related metrics (e.g., path length) significantly contributed to PC 1 in both tasks. Regarding PC 2, speed-related metrics (e.g., velocity, acceleration, jerk) of right-hand devices largely contributed to the tissue dissection task, while those of left-hand devices did in the suturing task. Regarding the three-group discrimination, in the tissue dissection task, the GBDT method was superior to the other methods (median accuracy: 68.6%). In the suturing task, SVM and PCA-SVM methods were superior to the GBDT method (57.4 and 58.4%, respectively). Regarding the two-group discrimination (experts vs. intermediates/novices), the GBDT method resulted in a median accuracy of 72.9% in the tissue dissection task, and, in the suturing task, the PCA-SVM method resulted in a median accuracy of 69.2%. Overall, the mocap-based credential system using machine-learning classifiers provides a correct judgment rate of around 70% (two-group discrimination). Together with motion analysis and wet-lab training, simulation training could be a practical method for objectively assessing the surgical competence of trainees.

Background Immune checkpoint inhibitors (ICIs) are increasingly being used to treat malignancies. Some patients experience immune-related adverse events (irAEs), which may affect any organ/tissue. IrAEs are occasionally fatal and usually have nonspecific symptoms. We developed a three-step application (https://irae-search.com/) to provide healthcare professionals with information on the diagnosis, treatment options, and published reports for 38 categories of irAEs encountered in clinical practice. Methods IrAEs reported in ≥5 cases were identified from articles published between October 2018 and August 2020 by searching Japanese (SELIMIC, JAPIC-Q Service, and JMED Plus) and international (MEDLINE, EMBASE, Derwent Drug File) databases. The cases’ symptoms were entered into the application to identify irAEs, which were verified using the reported diagnosis, to evaluate the application’s sensitivity and specificity. Results Overall, 1209 cases (1067 reports) were analyzed. The three most common categories of irAEs were pituitary or adrenal disorders (14% of cases), skin disorders (13%), and diabetes mellitus (10%). The top three primary diseases were lung cancer (364 cases), melanoma (286 cases), and renal cell carcinoma (218 cases). The average sensitivity was 90.8% (range 44.4%–100.0%) initially, and improved to 94.8% (range 83.3%–100.0%) after incorporating the symptoms reported in published cases into the application’s logic for two irAE categories. The average specificity was 79.3% (range 59.1% [thyroid disorders]–98.2% [arthritis]). Conclusion irAE Search is an easy-to-use application designed to help healthcare professionals identify potential irAEs in ICI-treated patients in a timely manner to facilitate prompt management/treatment. The application showed high sensitivity and moderate-to-high specificity for detecting irAEs.

This paper presents details of the development and validation of a measurement system for laparoscopic surgical procedures. An individual marker set is attached to each surgical instrument, and hence the developed system can simultaneously track multiple surgical instruments. The tracked surgical instruments can be exchanged during an operation. The movements of surgical instruments such as grasping forceps, scissors forceps, clip appliers, and needle holders are measured, and their tip positions, opening ratios, gripper rotation angles, and orientations are calculated online. Two strain gauges are attached to the gripper of the grasping forceps to measure the grasping point and force. In validation experiments, data from 46 cases of lymphadenectomy and renal parenchyma suturing using porcine cadaver organs performed by 44 subjects were acquired by measurement, and the movements of the surgical instruments used were recorded. A questionnaire survey regarding the operational feel about the surgical instruments was conducted, and the results show that this system has little impact on the operational feel.

Background: Virtual reality simulators allow trainees to perform repeated practice and provide objective dexterity metrics regarding their performance, which means that virtual reality–based surgical training is becoming a vital part of initial learning of basic laparoscopic surgical skills. However, its educational role in learning advanced procedures remains undetermined. We evaluated the validity of the laparoscopic radical nephrectomy module of the LapVision virtual reality simulator. Methods: Urologists, medical students, and a junior resident voluntarily participated in the present study, and they performed training with a laparoscopic left radical nephrectomy module. For construct validation, dexterity metrics calculated in the simulator and the mean score of Global Operative Assessment of Laparoscopic Skills evaluated by 2 experts' video review were compared according to the certification of Japanese Endoscopic Surgical Skill Qualification or previous surgical experience. Results: Ten experts (≥50 laparoscopic surgeries), 9 intermediates (11-49), and 14 novices (0-10) voluntarily participated in the present study. Regarding the construct validity, there was a significant difference in the total number of errors, blood loss, and Global Operative Assessment of Laparoscopic Skills score among the groups for both the Endoscopic Surgical Skill Qualification status and previous surgical experience. Conclusion: The present study demonstrated good construct validity for the LapVision nephrectomy module. Furthermore, global skill assessment was possible by experts' reviews, which indicates the usefulness of the virtual reality procedural module as a skill assessment tool. Virtual reality–based procedural simulation has marked potential to become a vital part of integrated laparoscopic training programs.

Abstract Purpose To determine the best method to contour the planning organ at risk volume (PRV) for the urethra, this study aimed to investigate the displacement of a Foley catheter in the urethra with a soft and thin guide-wire. Methods For each patient, the study used two sets of computed tomography (CT) images for radiation treatment planning (RT-CT): (1) set with a Foley urethral catheter (4.0 mm diameter) plus a guide-wire (0.46 mm diameter) in the first RT-CT and (2) set with a guide-wire alone in the second CT recorded 2 min after the first RT-CT. Using three fiducial markers in the prostate for image fusion, the displacement between the catheter and the guide-wire in the prostatic urethra was calculated. In 155 consecutive patients treated between 2011 and 2017, 5531 slices of RT-CT were evaluated. Results Assuming that ≥3.0 mm of difference between the catheter and the guide-wire position was a significant displacement, the urethra with the catheter was displaced significantly from the urethra with the guide-wire alone in > 20% of the RT-CT slices in 23.2% (36/155) of the patients. The number of patients who showed ≥3.0 mm anterior displacement with the catheter in ≥20% RT-CT slices was significantly larger at the superior segment (38/155) than at the middle (14/155) and inferior segments (18/155) of the prostatic urethra (p

Abstract Background Tumor endothelial cells (TECs) perform tumor angiogenesis, which is essential for tumor growth and metastasis. Tumor cells produce large amounts of lactic acid from glycolysis; however, the mechanism underlying the survival of TECs to enable tumor angiogenesis under high lactic acid conditions in tumors remains poorly understood. Methodology The metabolomes of TECs and normal endothelial cells (NECs) were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The expressions of pH regulators in TECs and NECs were determined by quantitative reverse transcription-PCR. Cell proliferation was measured by the MTS assay. Western blotting and ELISA were used to validate monocarboxylate transporter 1 and carbonic anhydrase 2 (CAII) protein expression within the cells, respectively. Human tumor xenograft models were used to access the effect of CA inhibition on tumor angiogenesis. Immunohistochemical staining was used to observe CAII expression, quantify tumor microvasculature, microvessel pericyte coverage, and hypoxia. Results The present study shows that, unlike NECs, TECs proliferate in lactic acidic. TECs showed an upregulated CAII expression both in vitro and in vivo. CAII knockdown decreased TEC survival under lactic acidosis and nutrient-replete conditions. Vascular endothelial growth factor A and vascular endothelial growth factor receptor signaling induced CAII expression in NECs. CAII inhibition with acetazolamide minimally reduced tumor angiogenesis in vivo. However, matured blood vessel number increased after acetazolamide treatment, similar to bevacizumab treatment. Additionally, acetazolamide-treated mice showed decreased lung metastasis. Conclusion These findings suggest that due to their effect on blood vessel maturity, pH regulators like CAII are promising targets of antiangiogenic therapy. Video Abstract Graphical abstract

Abstract Background Robot-assisted radical cystectomy is becoming a common treatment for bladder carcinoma. However, in comparison with open radical cystectomy, its cost-effectiveness has not been confirmed. Although few published reviews have compared total costs between the two surgical procedures, no study has compared segmental costs and explained their impact on total costs. Methods A systematic review was conducted based on studies on the segmental costs of open, laparoscopic, and robot-assisted radical cystectomy using PubMed, Web of Science, and Cochrane Library databases to provide insight into cost-effective management methods for radical cystectomy. The segmental costs included operating, robot-related, complication, and length of stay costs. A sensitivity analysis was conducted to determine the impact of the annual number of cases on the per-case robot-related costs. Results We identified two studies that compared open and laparoscopic surgeries and nine that compared open and robotic surgeries. Open radical cystectomy costs were higher than those of robotic surgeries in two retrospective single-institution studies, while robot-assisted radical cystectomy costs were higher in 1 retrospective single-institution study, 1 randomized controlled trial, and 4 large database studies. Operating costs were higher for robotic surgery, and accounted for 63.1–70.5% of the total robotic surgery cost. Sensitivity analysis revealed that robot-related costs were not a large proportion of total surgery costs in institutions with a large number of cases but accounted for a large proportion of total costs in centers with a small number of cases. Conclusions The results show that robot-assisted radical cystectomy is more expensive than open radical cystectomy. The most effective methods to decrease costs associated with robotic surgery include a decrease in operating time and an increase in the number of cases. Further research is required on the cost-effectiveness of surgeries, including quality measures such as quality of life and quality-adjusted life years.

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.

Abstract Background Difficult surgical procedures may result in a higher mental workload, leading to increased fatigue and subsequent errors. This study was aimed to investigate the effect of repeated simulation training in ureterorenoscopy in a high-fidelity setting on the performance and mental workload of novice operators. Methods Medical students voluntarily participated in the present simulation study. After a didactic and video-based lecture, they underwent simulation training involving a renal stone case, including a rigid cystoscope component (task 1, performing a WHO checklist, assembling a scope, and insertion of a guide-wire and an access sheath after examining the bladder) and a flexible ureterorenoscope component (task 2, retrieving a stone located in the upper calyx using a basket after inspecting the upper, middle, and lower calyx). Training was performed in a mock operating theater. Technical skills were assessed by one author (an experienced urologist) onsite using an Objective Structured Assessment of Technical Skills (OSATS) score at each training session. The mental workload was subjectively evaluated by the National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire after each training session. Results Seventeen students completed a minimum of 6 training sessions (male: female = 10: 7, median age of 22) over a median of 21 days (range, 10–32). In both tasks 1 and 2, the OSATS score improved over the 6 sessions with evidence of plateauing (MANOVA model, task 1: p

Abstract Background A prospective, randomised phase II study demonstrated clinical benefit of axitinib dose titration in a subset of treatment-naïve patients treated with axitinib for metastatic renal cell carcinoma. This analysis evaluated patient baseline characteristics that may impact overall survival (OS) with axitinib dose titration. Methods Following a 4-week lead-in period during which all patients received axitinib 5 mg twice-daily (bid); patients meeting the predefined randomisation criteria were randomly assigned to receive axitinib 5 mg bid plus either axitinib or placebo titration. In exploratory analyses, patients were grouped into those who achieved OS ≥24 versus

Abstract Introduction The incidence of prostate cancer in Japan continues to increase, necessitating the continued development of effective therapies and strategies. Recent advances in treatments have improved the prognosis of metastatic disease and highlighted the importance of treating bone metastases to reduce the incidence of skeletal complications and improve patients’ quality of life. With the increasing number of treatment options that have become available, including bone-targeted therapy with the alpha emitter radium-223 dichloride (Ra-223), Japanese clinicians are faced with making difficult decisions on the choice of optimal treatment strategy. In such situations, guidance based on expert opinions can be beneficial. Methods A panel meeting of 27 Japanese experts in the management of prostate cancer was held to share opinions and to establish consensus recommendations on key clinical questions. Panelists were asked to vote on more than 40 questions pertinent to prostate cancer, and the answers helped guide a comprehensive discussion. Results The panel reached a consensus on key topics related to the optimal treatment strategy for Ra-223 therapy, namely, that patients with symptomatic, metastatic castration-resistant prostate cancer (CRPC) would benefit most from the use of this agent and that this treatment therapy should be provided before chemotherapy. Other topics that achieved consensus included: monitoring for osteoporosis and providing treatment if necessary during androgen deprivation therapy; performing magnetic resonance imaging in the presence of discrepancies in bone scintigram and computed tomography scans; monitoring alkaline phosphatase during CRPC treatment; using osteoclast-targeting in patients with CRPC with bone metastases; and using osteoclast-targeted agents combined with Ra-223. Conclusion These consensus recommendations and the updated information which became available subsequent to the panel meeting included here provide useful information for clinicians to aid in designing optimal treatment strategies for their patients. Funding Bayer Yakuhin Ltd.

Sacrococcygeal teratoma (SCT) is the most common fetal and neonatal tumor. While SCT is often associated with urological problems, the association between SCT and a urogenital sinus (UGS) anomaly is rare. A concurrent UGS anomaly may be an acquired condition due to resection of SCT because it is rarely found at birth. In our case in whom fetal imaging study showed an abdominal cystic lesion, SCT with a UGS anomaly was suspected at birth and confirmed by endoscopy before resection of SCT during the neonatal period. These findings revealed that UGS anomaly may develop congenitally.

Background: Knowledge is increasing about TSC-Associated Neuropsychiatric Disorders (TAND), but little is known about the potentially confounding effects of intellectual ability (IA) on the rates of TAND across age, sex, and genotype. We evaluated TAND in (a) children vs. adults, (b) males vs. females, and (c) TSC1 vs. TSC2 mutations, after stratification for levels of IA, in a large, international cohort.Methods: Individuals of any age with a documented visit for TSC in the 12 months prior to enrolment were included. Frequency and percentages of baseline TAND manifestations were presented by categories of IA (no intellectual disability [ID, intelligence quotient (IQ)>70]; mild ID [IQ 50–70]; moderate-to-profound ID [IQ

He was born with markedly dilated left megaureter. Since it disturbed his oral intake after birth, left temporary cutaneous ureterostomy was created at 3 days of age. Since his left kidney was dysplastic, laparoscopic left nephroureterectomy was performed using the stoma site of cutaneous ureterostomy as a multi-channel port site at 15 months of age. He had no complications after surgery, and the postoperative wound appearance was good.This is the first report of the stoma site being used as a multi-channel port site in the urology field. This surgical approach provides good cosmetic outcomes. Keywords: Laparoscopy, Stoma site, Multi-channel port, Children

Abstract Background It has been described that the incidence of testicular microlithiasis is high in several congenital disorders which may be associated with testicular impairment and infertility. Several reports have shown that a prepubertal or pubertal hormonal abnormality in the pituitary-gonadal axis was identified in some patients with hypospadias that is one of the most common disorders of sex development. However, exact prevalence or risk factors of testicular microlithiasis in patients with hypospadias have not reported so far. In the present study, to clarify the prevalence and risk factors of testicular microlithiasis in patients with hypospadias, a retrospective chart review was performed. Methods Children with hypospadias who underwent testicular ultrasonography between January 2010 and April 2016 were enrolled in the present study. Severity of hypospadias was divided into mild and severe. The prevalence and risk factors of testicular microlithiasis or classic testicular microlithiasis were examined. Results Of 121 children, mild and severe hypospadias were identified in 66 and 55, respectively. Sixteen children had undescended testis. Median age at ultrasonography evaluation was 1.7 years old. Testicular microlithiasis and classic testicular microlithiasis were documented in 17 children (14.0%) and 8 (6.6%), respectively. Logistic regression analysis revealed that presence of undescended testis was only a significant factor for testicular microlithiasis and classic testicular microlithiasis. The prevalence of testicular microlithiasis or classic testicular microlithiasis was significantly higher in children with undescended testis compared to those without undescended testis (testicular microlithiasis; 43.8% versus 9.5% (p = 0.002), classic testicular microlithiasis; 37.5% versus 1.9% (p

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.

Abstract Background Ureterocalicostomy is indicated mainly in cases with failed pyeloplasty or with a completely intrarenal pelvis. While there have been several case series reported in adults, laparoscopic ureterocalicostomy in pediatric cases has rarely been reported. We report a case of pure laparoscopic ureterocalicostomy for ureteropelvic junction obstruction in an Asian female child. Case presentation A 10-year-old female patient was referred to our hospital due to right high-grade hydronephrosis and a right renal stone, which was detected due to hematuria. Laparoscopic pyelolithotomy and ureterocalicostomy were indicated because of the completely intrarenal pelvis with thinning of the cortex, especially at the lower calyx. A transperitoneal approach was implemented in a lateral flank position with four trocars. After exposing the renal hilum, the renal stone was extracted without lithotripsy by making a small longitudinal incision at the ureteropelvic junction. Then, the ureter was transected, and the renal pelvis was closed. A 2-cm incision was made at the lower calyx. Uretero-caliceal anastomosis was completed in a running fashion using 5-0 absorbable sutures. The operation time was 379 min. The postoperative course was uneventful. Postoperative imaging studies showed marked improvement of the right hydronephrosis. Conclusion Laparoscopic ureterocalicostomy is a safe and feasible treatment for selected patients with complicated ureteropelvic junction obstruction, even in the pediatric population.

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.

Background. Mycophenolic acid (MPA) concentration measured by homogeneous particle-enhanced turbidimetric inhibition immunoassay (PETINA) may be overestimated due to its cross-reactivity with pharmacologically inactive MPA glucuronide (MPAG), as well as other minor metabolites, accumulated with renal function impairment or co-administered cyclosporine A. In contrast, high-performance liquid chromatography (HPLC) is precise because it can exclude the cross-reactivity. In this study, we assumed HPLC values for MPA (HPLC-MPA) as a reference and aimed to develop a formula correcting PETINA values for MPA (PETINA-MPA) to more precisely reflect HPLC-MPA. Methods. MPA trough concentrations were measured both by HPLC-UV and PETINA in 39 samples issued from 39 solid-organ transplant recipients. MPAG concentrations were also measured using HPLC UV assay. We determined the impacts of renal function and coadministered calcineurin inhibitor on concentrations of MPA and MPAG measured by HPLC. Then, we evaluated the difference between PETINA-MPA and HPLC-MPA. Finally, we develop a formula to reflect HPLC-MPA by using multilinear regression analysis. Results. MPAG concentration was negatively correlated with estimated glomerular filtration rate (eGFR) (R2 = 0.376, P < 0.001), although MPA was not correlated with eGFR. There were no significant differences in MPA or MPAG concentrations per dose between the patients who were co-administered tacrolimus versus cyclosporine A. Finally, we developed the formulas to reflect HPLC-MPA: Formula 1: Estimated MPA concentration = 0.048 + 0.798 × PETINA‐MPA Formula 2: Estimated MPA concentration = − 0.059 + 0.800 × PETINA‐MPA + 0.002 × eGFR However, there was no significant improvement in the coefficient of determination with addition of eGFR in the formula, suggesting that HPLC-MPA can be well predicted by only 1 variable, PETINA-MPA. Conclusions. This study developed a formula so that PETINA-MPA can be corrected to more precisely reflect HPLC-MPA.

B cells constitute a complex system of antigen-presenting cells (APCs) and exist as distinct subsets that differ in their lineage affiliation, surface molecule expression, and biological function, thus potentially regulating the immune response. In this study, we investigated the immune-regulatory roles of murine B cell subsets as regulatory APCs targeting alloreactive T cells. Either splenic B cells, peritoneal cavity (PerC) B cells, or non-B cells from Balb/c mice were intravenously injected into B6 mice. Serum levels of anti-Balb/c antibodies in the recipients of PerC B cells were significantly lower than those in the recipients of splenic B cells and PerC non-B cells, as determined over a 4-week period after the injection. Mixed-lymphocyte reaction (MLR) assays using splenocytes from the B6 mice at 2 weeks after the injection revealed the significantly reduced anti-Balb/c T cell-responses in the recipients of PerC B cells, as compared to those in the recipients of splenic B cells or untreated control mice. Since PerC B cells contained MHC class II+ CD80+ CD86+ PD-L1+ PD-L2+ cells among the CD5+ B-1a cell subset, PerC B cells from Balb/c mice were pre-incubated with anti-PD-L1/PD-L2 mAbs prior to injection. This treatment abrogated their immune-regulatory effects on anti-Balb/c T cells in the MLR assays. In addition, the inoculation with Balb/c PerC B cells significantly prolonged the survival of subsequently grafted Balb/c hearts in B6 mouse recipients, whereas that with SPL B cells did not. These findings indicate that the PerC B cells, including PD-L1/PD-L2 B-1a cells, may suppress T cells responding to allostimulation, and thus may be optimal for donor lymphocyte injection.

Tumor angiogenesis research and antiangiogenic drug development make use of cultured endothelial cells (ECs) including the human microvascular ECs among others. However, it has been reported that tumor ECs (TECs) are different from normal ECs (NECs). To functionally validate antiangiogenic drugs, cultured TECs are indispensable tools, but are not commercially available. Primary human TECs are available only in small quantities from surgical specimens and have a short life span in vitro due to their cellular senescence. We established immortalized human TECs (h-imTECs) and their normal counterparts (h-imNECs) by infection with lentivirus producing simian virus 40 large T antigen and human telomerase reverse transcriptase to overcome the replication barriers. These ECs exhibited an extended life span and retained their characteristic endothelial morphology, expression of endothelial marker, and ability of tube formation. Furthermore, h-imTECs showed their specific characteristics as TECs, such as increased proliferation and upregulation of TEC markers. Treatment with bevacizumab, an antiangiogenic drug, dramatically decreased h-imTEC survival, whereas the same treatment failed to alter immortalized NEC survival. Hence, these h-imTECs could be a valuable tool for drug screening to develop novel therapeutic agents specific to TECs or functional biological assays in tumor angiogenesis research.

PURPOSE: To evaluate postoperative renal function and risk factors for the loss of renal function in patients who had undergone radical cystectomy. MATERIALS AND METHODS:A retrospective single institutional study evaluated 70 patients, including 54 men and 16 women who underwent radical cystectomy. The median follow-up period was 34.5 months (range, 12 to 228 months). In this cohort, four types of urinary diversions were studied, including ilealneobladder (n = 24), ileocecalneobladder (n = 12), ileal conduit (n = 25), and cutaneous ureterostomy (n = 9). Postoperative changes in renal function were reviewed, and the estimated serum creatinine-based glomerular filtration rate (eGFR) was calculated. The variables analyzed were age, a prior history of hypertension or diabetes mellitus, pre-operative renal function, type of urinary diversion, the postoperative occurrence of acute pyelonephritis, and the presence of chemotherapy. RESULTS: The mean eGFR was 74.6 (range, 15.2 to 155.1) mL/min/1.73 m2 before surgery and 63.6 (range, 8.7 to 111.5) mL/min/1.73 m2 at the last follow-up. The 10-year renal deterioration-free interval was 63.8%. Multivariate analysis showed that a postoperative episode of acute pyelonephritis [Odds Ratio (OR), 3.21; 95% Confidence Interval (CI), 1.14 to 9.02; P = .03] and the presence of chemotherapy (OR, 3.27; 95% CI, 1.33 to 8.01; P = .01) were significant adverse factors. CONCLUSION: Twenty-four (34.2%) patients demonstrated reduced renal function during the follow-up period. Postoperative episodes of acute pyelonephritis and the presence of chemotherapy were found to be significant adverse factors.

Sexually dimorphic brain development and behavior are known to be influenced by sex hormones exposure in prenatal periods. On the other hand, second-to forth digit ratio (2D/4D) has been used as an indirect method to investigate the putative effects of prenatal exposure to androgen. In the present study, we herein investigated the relationship between gender-role play behavior and the second-to-fourth digit ratio (2D/4D), which has been used as an indirect method to investigate the putative effects of prenatal exposure to androgens, in school-aged children. Among 4981 children who became 8 years old by November 2014 and were contactable for this survey by The Hokkaido Study of Environment and Children's Health, 1631 (32.7%), who had data for 2D/4D and Pre-school Activities Inventory (PSAI) as well as data for the survey at baseline, were available for analysis. Parents sent reports of PSAI on the sex-typical characteristics, preferred toys, and play activities of children, and black and white photocopies of the left and right hand palms via mail. PSAI consisted of 12 masculine items and 12 feminine items, and a composite score was created by subtracting the feminine score from the masculine score, with higher scores representing masculine-typical behavior. While composite scores in PSAI were significantly higher in boys than in girls, 2D/4D was significantly lower in boys than in girls. Although the presence or absence of brothers or sisters affected the composite, masculine, and feminine scored of PSAI, a multivariate regression model revealed that 2D/4D negatively correlated with the composite scores of PSAI in boys, whereas no correlation was found in girls. Although 2D/4D negatively correlated with the masculine score in boys and girls, no correlation was observed between 2D/4D and the feminine score. In conclusion, although social factors, such as the existence of brother or sisters, affect dimorphic brain development and behavior in childhood, the present study revealed that the prenatal hormonal environment was an important factor influencing masculine-typical dimorphic brain development and behavior in school-aged children.