Ureteroscopy for urolithiasis in bedridden patients: it is feasible and acceptable.

PURPOSE: To investigate the safety of transurethral ureteroscopy (URS) for urolithiasis in bedridden patients and to identify bedridden patient-specific risk factors for postoperative complications. METHODS: The patients who underwent URS for urolithiasis were divided into bedridden patients and good performance status (PS) patients, and the groups were compared regarding their clinical characteristics and postoperative complications. A multivariable logistic regression analysis was performed to evaluate independent predictors of postoperative febrile urinary tract infection (fUTI). RESULTS: A total of 1626 patients were included, 276 in the bedridden patient group, and 1350 in the good PS patient group. The bedridden patient group had a significantly higher age and higher proportion of females and had multiple comorbidities. In 77 patients (27.9%), 88 postoperative complications developed for the bedridden patient group. Clavien-Dindo grade III or IV complications were observed in only 8 patients. No grade V complications were observed. The most common complication was fUTI. The frequency of fUTI with grade III or IV for the bedridden patient group (2.2%) was higher compared with the good PS patient group (0.5%), but the difference was not statistically significant (p = 0.13). Bedridden patient-specific risk factors for fUTI included female sex, diabetes mellitus, cerebrovascular comorbidities, lower extremity contracture, and prolonged operative time. CONCLUSION: URS for urolithiasis is a feasible and acceptable procedure in bedridden patients, despite the moderate rate of postoperative complications. The identified risk factors provide a framework for risk stratification and individualized care in this unique patient population.

[A Case of Metastatic Renal Cancer Responding to Sunitinib as the Eighth Line Therapy].

A 62-year-old male presenting with gross hematuria and right renal mass was referred to our Urology Department. Computed tomography revealed a right renal mass, with multiple pulmonary lesions. He underwent right nephrectomy for highly suspected renal cell carcinoma with pulmonary metastases (cT3aN0M1). The pathological diagnosis was clear cell renal cell carcinoma, pT1b. Following surgery, he was treated with multiple regimens of chemotherapy, ranging from interferon alpha, multiple tyrosine kinase inhibitors such as sorafenib, axitinib, pazopanib and cabozantinib, everolimus, and nivolumab, all of which were discontinued after its induction, either due to adverse events or progressive disease. He was finally administered Sunitinib as the 8th line "last-ditch" treatment, which resulted in significant tumor shrinkage. No disease progression has been observed 25 months after initiating sunitinib administration.

[Intraoperative Evaluation of Ureteral Blood Flow Using Indocyanine Green Fluorescence imaging on Living-Donor Kidney Transplantation].

Ureteral stenosis occurs in 2-10% after kidney transplantation. Most are caused by ischemia of the distal ureter and are difficult to manage. There is no standard method for evaluating ureteral blood flow during surgery, and it is left to the judgement of the operator. Indocyanine green (ICG) is used not only for a liver or cardiac function test but also for an assessment of tissue perfusion. We evaluated the intraoperative ureteral blood flow under a surgical light and by ICG fluorescence imaging in 10 living-donor kidney transplant patients between April 2021 and March 2022. No ureteral ischemia was detected under the surgical light, but ICG fluorescence imaging revealed/decreased blood flow in 4 of the 10 patients (40%). Further resection was performed in these 4 patients to increase the blood flow, and the median resection length was 1.0cm (0.3-2.0). The postoperative course was uneventful in all 10 patients, and no ureter-related complications were observed. ICG fluorescence imaging is a useful method for evaluating ureteral blood flow and is expected to help reduce complications caused by ureteral ischemia.

[Risk Factors of Antiresorptive Agent-Related Osteonecrosis of the Jaw in Prostate Cancer Patients with Bone Metastases].

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a severe adverse event associated with use of bone resorption inhibitors (BRIs), such as zoledronic acid and denosumab. Based on the results of phase 3 clinical trials for BRIs, the frequency of ARONJ is reported to be 1 to 2%, but the actual frequency could be higher. We investigated 173 patients with prostate cancer with bone metastases who were treated either with zoledronic acid or denosumab at our hospital between July 2006 and June 2020. ARONJ occurred in 13 patients (8%); i.e., ten out of 159 patients (6%) who were treated with zoledronic acid, and three out of 14 patients (21%) who were treated with denosumab. Multivariate analysis showed that longer duration of BRI exposure and dental treatment before the initiation of BRI are associated with risk of ARONJ. ARONJ is associated with decreased mortality but the association is not significant. Generally, the occurrence of ARONJ may be underestimated; therefore, further studies are warranted to determine the actual frequency of ARONJ.

[Challenging Case of Primary Renal Castleman's Disease Accompanied with Bacterial Pyelonephritis].

Castleman's disease is a rare lymphoproliferative disease, mostly found in the mediastinum. The number of Castleman's disease cases involving the kidneys is still limited. We report a case of primary renal Castleman's disease sporadically detected during a regular health check-up as pyelonephritis with ureteral stones. In addition, computed tomography showed renal pelvic and ureteral wall thickening with paraaortic lymphadenopathy. A lymph node biopsy was performed, but it did not confirm either malignancy or Castleman's disease. The patient underwent open nephroureterectomy for diagnostic and therapeutic purposes. The pathological diagnosis was renal and retroperitoneal lymph node Castleman's disease with pyelonephritis.

[The Effect of Naldemedine Tosylate on the Postoperative Course of Robot-Assisted Radical Cystectomy].

Radical cystectomy is an invasive procedure frequently followed by postoperative complications. Although the protocol of enhanced recovery after surgery (ERAS) is used in the postoperative course, several components of the ERAS protocol may increase the workload of medical workers. In this study, we added naldemedine tosylate only to routine postoperative management instead of using the ERAS protocol and evaluated the effect on the postoperative course of robot-assisted radical cystectomy (RARC). We retrospectively investigated 58 patients who underwent RARC from May 2015 to February 2022 at our hospital and evaluated the postoperative complications, such as ileus and urinary tract infections, and, length of hospital stay (LOS). We used naldemedine tosylate for the patients who underwent RARC after November 2019. As a result, naldemedine tosylate reduced 26.8% of postoperative complications within 30 days after the operation (p＝0.041) and shortened LOS 8 days (p＝0.018). Naldemesine tosylate improved the postoperative course of RARC.

Challenges and Applications to Operando and In Situ TEM Imaging and Spectroscopic Capabilities in a Cryogenic Temperature Range.

ConspectusIn this Account, we describe the challenges and promising applications of transmission electron microscopy (TEM) imaging and spectroscopy at cryogenic temperatures. Our work focuses on two areas of application: the delay of electron-beam-induced degradation and following low-temperature phenomena in a continuous and variable temperature range. For the former, we present a study of LiMn1.5Ni0.5O4 lithium ion battery cathode material that undergoes electron beam-induced degradation when studied at room temperature by TEM. Cryogenic imaging reveals the true structure of LiMn1.5Ni0.5O4 nanoparticles in their discharged state. Improved stability under electron beam irradiation was confirmed by following the evolution of the O K-edge fine structure by electron energy-loss spectroscopy. Our results demonstrate that the effect of radiation damage on discharged LiMn1.5Ni0.5O4 was previously underestimated and that atomic-resolution imaging at cryogenic temperature has a potential to be generalized to most of the Li-based materials and beyond. For the latter, we present two studies in the imaging of low-temperature phenomena on the local scale, namely, the evolution of ferroelectric and ferromagnetic domains walls, in BaTiO3 and Y3Fe5O12 systems, respectively, in a continuous and variable temperature range. Continuous imaging of the phase transition in BaTiO3, a prototypical ferroelectric system, from the low-temperature orthorhombic phase continuously up to the centrosymmetric high-temperature phase is shown to be possible inside a TEM. Similarly, the propagation of domain walls in Y3Fe5O12, a magnetic insulator, is studied from ∼120 to ∼400 K and combined with the application of a magnetic field and electrical current pulses to mimic the operando conditions as in domain wall memory and logic devices for information technology. Such studies are promising for studying the pinning of the ferroelectric and magnetic domains versus temperature, spin-polarized current, and externally applied magnetic field to better manipulate the domain walls. The capability of combining operando TEM stimuli such as current, voltage, and/or magnetic field with in situ TEM imaging in a continuous cryogenic temperature range will allow the uncovering of fundamental phenomena on the nanometer scale. These studies were made possible using a MEMS-based TEM holder that allowed an electron-transparent sample to be transferred and electrically contacted on a MEMS chip. The six-contact double-tilt holder allows the alignment of the specimen into its zone axis while simultaneously using four electrical contacts to regulate the temperature and two contacts to apply the electrical stimuli, i.e., operando TEM imaging. This Account leads to the demonstration of (i) the high-resolution imaging and spectroscopy of nanoparticles oriented in the desired [110] zone-axis direction at cryogenic temperatures to mitigate the electron beam degradation, (ii) imaging of low-temperature transitions with accurate and continuous control of the temperature that allowed single-frame observation of the presence of both the orthorhombic and tetragonal phases in the BaTiO3 system, and (iii) magnetic domain wall propagation as a function of temperature, magnetic field, and current pulses (100 ns with a 100 kHz repetition rate) in the Y3Fe5O12 system.

[Efficacy of Combination Chemotherapy of Gemcitabine and Nedaplatin for Squamous Cell Carcinoma of the Urinary Tract : Experience of Four Cases].

We report the use of combination chemotherapy of gemcitabine (800 mg/m² on day1 and 8) and nedaplatin (60 mg/m² on day 1), including neoadjuvant therapy in four cases of squamous cell carcinoma of the urinary tract. In each case, the dose was reduced after assessing the performance status and renal function of the patient. Among the four cases, the best overall outcome was complete response in one case, partial response in two cases, and stable disease in one case. The main adverse event observed was thrombocytopenia; however, no serious adverse events were observed, and this regimen was safely administered. Therefore, we believe that this regimen could be an effective treatment option for progressive squamous cell carcinoma originating from the urinary tract.

[A Case of Bladder Cancer Treated with Arterial Stent-Grafting to Prevent Uretero-Arterial Fistula Due to Radiation Therapy for Metastasis].

A 66-year-old male with bladder cancer underwent radical cystectomy and ileal conduit construction. The pathological diagnosis was urothelial carcinoma with squamous differentiation (pT3b). Computed tomography (CT) 18 months postoperatively revealed a right external iliac lymph node metastasis. He was treated with systemic chemotherapy after placement of bilateral ureteral stents, but CT following chemotherapy revealed an increase in the size of the metastasis, and the patient was diagnosed with progressive disease. Radiotherapy to the metastasis was selected as local therapy, but the patient was at risk of an uretero-arterial fistula because the right external iliac artery and the right ureter adjacent to the metastasis were involved in the irradiated field. The right external iliac lymph node metastasis was irradiated with a dose of 50 Gy after stent grafting for the right external iliac artery to prevent an ureteroarterial fistula. He had no adverse events, including hematuria after radiotherapy, but died of cancer cachexia 12 months after radiotherapy.

Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1 in normal and diseased bladder detrusor muscles: a clinico-pathological study.

BACKGROUND: To investigate the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant that functions via PTH1R. We hypothesized that suppression of this axis could be involved in the pathogenesis of bladder disease. METHODS: PTH1R expression in clinical samples was examined by immunohistochemistry. Normal kidney tissue from a patient with renal cancer and bladder specimens from patients undergoing ureteral reimplantation for vesicoureteral reflux or partial cystectomy for urachal cyst were examined as normal control organs. These were compared with 13 diseased bladder specimens from patients undergoing bladder augmentation. The augmentation patients ranged from 8 to 31 years old (median 15 years), including 9 males and 4 females. Seven patients had spinal disorders, 3 had posterior urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome). RESULTS: Renal tubules, detrusor muscle and blood vessels in normal control bladders stained positive for PTH1R. According to preoperative urodynamic studies of augmentation patients, the median percent bladder capacity compared with the age-standard was 43.6% (range 1.5-86.6%), median intravesical pressure at maximal capacity was 30 cmH2O (range 10-107 cmH2O), and median compliance was 3.93 ml/cmH2O (range 0.05-30.3 ml/cmH2O). Detrusor overactivity was observed in five cases (38.5%). All augmented bladders showed negative stainings in PTH1R expression in the detrusor tissue, but positive staining of blood vessels in majority of the cases. CONCLUSIONS: Downregulation of PTH1R may be involved in the pathogenesis of human end-stage bladder disease requiring augmentation.

[Clinical Characteristics of Prostate Ductal Adenocarcinoma in Kyoto University Hospital].

Prostate ductal adenocarcinoma is a rare variant of prostate cancer and considered to be more aggressive than the common acinar type of adenocarcinoma. The appropriate treatment guideline for prostate ductal adenocarcinoma has not been established. The aim of the present study was to examine the clinical characteristics and the effectiveness of treatment for prostate ductal adenocarcinoma. From 2005 to 2012, 41 patients were diagnosed to have prostate ductal adenocarcinoma in Kyoto University Hospital. The mean±SD age was 68.6±7.0 years, and the median (range) initial serum PSA level was 9.3 (3.7-217) ng/ml. Among 17 patients who underwent radical prostatectomy, 10 (58.8%) had pT3 disease and 5 (29.4%) had biochemical recurrence during median follow-up of 22.9 months. Out of 19 patients treated with definitive EBRT with endocrine therapy, 2 patients (10.5%) experienced biochemical recurrence with median follow-up of 37.3 months. Five patients were treated with endocrine therapy alone, and 2 (40.0%) of them died of prostate ductal adenocarcinoma. In conclusion, patients with prostate ductal adenocarcinoma were more likely diagnosed as locally advanced diseases than those with prostate acinar adenocarcinoma. However, for patients without metastasis, either surgery or EBRT with endocrine therapy is effective with good prognosis.

Novel constant-pressure irrigation technique for the treatment of renal pelvic tumors after ipsilateral ureterectomy.

We herein report a case of a renal pelvic tumor that developed in the residual left renal pelvis after right nephroureterectomy, left ureterectomy and total cystectomy in a patient with multiple urothelial tumors. The tumor was endoscopically ablated through a nephrostomy tract, and mitomycin C irrigation was carried out. We designed a novel constant-pressure irrigation system for effective and safe irrigation into the closed space of the renal pelvis. We created a hole in the urine bag tube, inserted a 5-Fr open-end ureteral catheter through the hole and kept the tip of the catheter at the end of the nephrostomy tube. The urine bag tube was placed 20 cm above the kidney level, and mitomycin C was continuously irrigated into the renal pelvis for 1 h. Six-weekly treatments were carried out, and tumor recurrence was not identified for 1 year.

[Usefulness of comparing of magnetic resonance imaging (MRI) findings prior to repeat biopsy and negative initial biopsy as a decision-making method for repeat prostate biopsy].

We retrospectively reviewed the data from a cohort of 44 patients with one initial negative transrectal ultrasound-guided prostate biopsy who underwent a repeat biopsy from 2006 to 2013. At each biopsy session, we checked patient age, serum prostate specific antigen (PSA), prostate volume, PSA density, PSA velocity, months from the initial biopsy session, multiparametric magnetic resonance imaging (MRI) findings (T2-weighted, dynamic contrast-enhanced and diffusion-weighted, 1.5 Tesla pelvic-phased array) prior to repeat biopsy and initial negative biopsy. Mean age was 68.2±8.82 years. PSA was 11.5±7.65 ng/ml before repeat biopsy. Prostate cancer was detected in 15 (34.0%) patients at repeat biopsy. In univariate and multivariate analysis, positive MRI findings before repeat biopsy were significant independent predictors of a positive repeat biopsy. At per patient analysis, the sensitivity, specificity, positive and negative predictive values were 66.6, 68.9, 71.4 and 80.0% for MRI before repeat biopsy. No suspicious lesion on MRI before repeat biopsy was relevant to negative biopsy. According to the comparison of MRI findings prior to repeat biopsy and negative initial biopsy, suspicious MRI findings at the peripheral zone before repeat biopsy and initial negative biopsy were relevant to a high cancer detection rate (83.3%) at repeat prostate biopsy. These results suggested that the absence of a suspicious lesion on MRI before repeat biopsy could guide the avoidance of repeat biopsy and suspicious MRI findings at the peripheral zone before repeat biopsy and initial negative biopsy could guide repeat biopsy.

[Small cell carcinoma of the bladder].

We retrospectively reviewed the records of 11 patients with small cell carcinoma of the bladder, who were diagnosed at Kyoto University Hospital between June 1995 and November 2010. The median age was 79 years. Two patients had stage I disease, 4 had stage II disease, 2 had stage III disease, and 3 had stage IV disease. All 3 patients with stage IV disease had metastatic disease. They had very poor prognosis with a median survival of only 9.1 months (range 3.2-13.0 months). Of 8 patients without metastatic disease, 3 patients who had been treated with neoadjuvant chemotherapy followed by cystectomy had longterm survival. The median survival of these 3 patients was 85.5 months (range 38.0-102.8 months), and all of them are still alive without cancer. The median survival of the other 5 patients was 12.6 months (range 9. 9-33. 8 months). There were significant differences in survival between patients with neoadjuvant chemotherapy followed by cystectomy and with other treatments (p＝0.024). In conclusion, these results suggested that neoadjuvant chemotherapy followed by cystectomy could cure patients with small cell carcinoma of the bladder without metastatic disease.

[Cross-cultural validated adaptation of dysfunctional voiding symptom score (DVSS) to Japanese language and cognitive linguistics in questionnaire for pediatric patients].

PURPOSE: Validated questionnaire for evaluation of pediatric lower urinary tract symptoms (LUTS) is of a great need. We performed cross-cultural validated adaptation of Dysfunctional Voiding Symptom Score (DVSS) to Japanese language, and assessed whether children understand and respond to questionnaire correctly, using cognitive linguistic approach. METHODS: We translated DVSS into two Japanese versions according to a standard validation methodology: translation, synthesis, back-translation, expert review, and pre-testing. One version was written in adult language for parents, and the other was written in child language for children. Pre-testing was done with 5 to 15-year-old patients visiting us, having normal intelligence. A specialist in cognitive linguistics observed the response by children and parents to DVSS as an interviewer. When a child could not understand a question without adding or paraphrasing the question by the parents, it was defined as 'misidentification'. RESULTS: We performed pretesting with 2 trial versions of DVSS before having the final version. The pre-testing for the first trial version was done for 32 patients (male to female ratio was 19 : 13). The pre-testing for the second trial version was done for 11 patients (male to female ratio was 8 : 3). In DVSS in child language, misidentification was consistently observed for representation of time or frequency. We completed the formal validated translation by amending the problems raised in the pre-testing. CONCLUSION: The cross-cultural validated adaptation of DVSS to child and adult Japanese was completed. Since temporal perception is not fully developed in children, caution should be taken for using the terms related with time or frequency in the questionnaires for children.

Sterile versus non-sterile gloves during cystoscopy: A randomized prospective single-blind study.

Objective: The objective of this study is to evaluate the need for sterile gloves during cystoscopy by comparing the incidence of UTI symptoms between patients in whom the procedure is performed with non-sterile gloves with those performed with non-sterile gloves. Patients and Methods: This study had a randomized, prospective, single-blind design and included patients aged >20 years who underwent cystoscopy in either of two outpatient clinics between September 2015 and November 2021. The patients were allocated to a sterile group or a non-sterile group. Only the urologists were aware of whether or not the gloves were sterile. The patients were instructed to report any symptoms suggestive of UTI after cystoscopy. Results: A total of 1258 patients were enrolled in the sterile group and 1376 in the non-sterile group. Symptoms of UTI were reported by six patients (0.48%) in the sterile group and six (0.44%) in the non-sterile group. The between-group difference was not statistically significant (p = 0.88). Conclusion: It is not necessary to use sterile gloves during routine cystoscopy.

Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development.

Overactive bladder (OAB) is a pervasive clinical problem involving alterations in both neurogenic and myogenic activity. While there has been some progress in understanding neurogenic inputs to OAB, the mechanisms controlling myogenic bladder activity are unclear. We report the involvement of myocardin (MYOCD) and microRNA-1 (miR-1) in the regulation of connexin 43 (GJA1), a major gap junction in bladder smooth muscle, and the collective role of these molecules during post-natal bladder development. Wild-type (WT) mouse bladders showed normal development from early post-natal to adult including increases in bladder capacity and maintenance of normal sensitivity to cholinergic agents concurrent with down-regulation of MYOCD and several smooth muscle cell (SMC) contractile genes. Myocardin heterozygous-knockout mice exhibited reduced expression of Myocd mRNA and several SMC contractile genes concurrent with bladder SMC hypersensitivity that was mediated by gap junctions. In both cultured rat bladder SMC and in vivo bladders, MYOCD down-regulated GJA1 expression through miR-1 up-regulation. Interestingly, adult myocardin heterozygous-knockout mice showed normal increases in bladder and body weight but lower bladder capacity compared to WT mice. These results suggest that MYOCD down-regulates GJA1 expression via miR-1 up-regulation, thereby contributing to maintenance of normal sensitivity and development of bladder capacity.

Late recurrence of nonseminomatous germ cell tumor successfully treated with intensity-modulated radiation therapy.

We report the case of a 41-year-old man with a late recurrence of nonseminomatous germ cell tumor, which was successfully treated with intensity-modulated radiation therapy. For the residual retrocrural tumor invading the 11th and 12th thoracic vertebrae with an abnormal level of tumor marker (α-fetoprotein: 23.2 ng/ml) after salvage chemotherapy, chemotherapy could not be continued due to its neurotoxicity, and surgery could not be performed due to the location. In this situation, intensity-modulated radiation therapy achieved a complete response of tumor marker. The patient remained in complete clinical remission after 3 years. The efficacy of radiotherapy, especially intensity-modulated radiation therapy, for a nonseminomatous germ cell tumor is discussed.

[Percutaneous renal mass biopsy after indeterminate diagnostic imaging results].

We conducted a retrospective study to examine the efficacy of renal mass biopsies in our hospital. Twenty-six patients (18 male, 8 female ; median age, 69 years ; range, 42-85 years) with renal masses were divided into two groups. Group 1 (n＝9) underwent renal mass biopsies after completion of diagnostic imaging tests that needed a pathological diagnosis before treatment other than extirpative surgery, and group 2 (n＝17) underwent renal mass biopsies after completion of indeterminate diagnostic imaging tests that did not rule out malignancy. The median tumor size was 2.8cm (range, 0.8-15 cm), and the median number of biopsy cores obtained was two (range, 2-4). There were no biopsy-associated complications that required intervention. In group 1, 100% (9 of 9) of the renal mass biopsies were diagnostic, and the pathological findings corresponded to the respective diagnosis obtained by imaging tests, most of which were clear cell carcinoma. In group 2, 59% (10 of 17) of the biopsies were diagnostic. The imaging characteristics of the seven nondiagnostic biopsies in group 2 were low blood flow and poor peripheral clarity. On the other hand, renal mass biopsies were indispensable for some patients in group 2 in whom the pathological findings led to a decision of treatment strategy. In conclusion, renal mass biopsies should be considered in view of their ability to compensate for limitations of imaging tests and their low frequency of complications.

[Pseudomyxoma peritonei arising from urachal carcinoma].

A 77-year-old man was diagnosed with urachal cyst, but had not been followed-up because of his severe dementia. He visited our department complaining of mucinuria. Ultrasonography showed a tumor with heterogeneous contents above the bladder. Mucinousfluid was found by cystoscopic examination. After the fluid was removed, a non-papillary tumor with mucin secretion was identified at the dome of the bladder. Computed tomography revealed that the peritoneal cavity was filled with a mucinous tumor. Peritonitis was suspected because of the existence of free air and abdominal rebound tenderness, and emergent surgery was performed. Bowel perforation was not found. Tumors could not be removed and the tissue biopsy was performed. It was pathologically diagnosed as pseudomyxoma peritonei arising from urachal carcinoma.