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Transurethral procedures such as direct vision internal urethrotomy and urethral dilation have been the traditional treatments for urethral strictures. However, transurethral procedures are associated with high recurrence rates, resulting in many uncured cases and prompting major international urological societies to recommend urethroplasty as the standard treatment owing to its high success rate. In contrast, many Japanese general urologists have little doubts about treating urethral strictures with transurethral treatment. Therefore, urethral stricture treatments in Japan are not in line with those used in other countries. To address this, the Trauma, Emergency Medicine, and Reconstruction Subcommittee of the Japanese Urological Association has developed guidelines to offer standardized treatment protocols for urethral stricture, based on international evidence and tailored to Japan's medical landscape. These guidelines target patients with a clinically suspected urethral stricture and are intended for urologists and general practitioners involved in its diagnosis and treatment. Following the Minds Clinical Practice Guideline Development Manual 2020, the committee identified eight critical clinical issues and formulated eight clinical questions using the "patient, intervention, comparison, and outcome" format. A comprehensive literature search was conducted. For six clinical questions addressed by the existing guidelines or systematic reviews, the level of evidence was determined by qualitative systematic reviews. Quantitative systematic reviews and meta‐analyses were performed for the two unique clinical questions. The recommendation grades were determined using the Delphi method and consensus by the committee. These guidelines will be useful to clinicians in daily practice, especially those involved in the care of urethral strictures. [ABSTRACT FROM AUTHOR]

The Japanese Urological Association's guidelines for the treatment of renal trauma were published in 2016. In conjunction with its revision, herein, we present the new guidelines for overall urotrauma. Its purpose is to provide standard diagnostic and treatment recommendations for urotrauma, including iatrogenic trauma, to preserve organ function and minimize complications and fatality. The guidelines committee comprised urologists with experience in urotrauma care, selected by the Trauma and Emergency Medicine Subcommittee of the Specialty Area Committee of the Japanese Urological Association, and specialists recommended by the Japanese Association for the Surgery of Trauma and the Japanese Society of Interventional Radiology. The guidelines committee established the domains of renal and ureteral, bladder, urethral, and genital trauma, and determined the lead person for each domain. A total of 30 clinical questions (CQs) were established for all domains; 15 for renal and ureteral trauma and five each for the other domains. An extensive literature search was conducted for studies published between January 1, 1983 and July 16, 2020, based on the preset keywords for each CQ. Since only few randomized controlled trials or meta‐analyses were found on urotrauma clinical practice, conducting a systematic review and summarizing the evidence proved challenging; hence, the grade of recommendation was determined according to the 2007 "Minds Handbook for Clinical Practice Guidelines" based on a consensus reached by the guidelines committee. We hope that these guidelines will be useful for clinicians in their daily practice, especially those involved in urotrauma care. [ABSTRACT FROM AUTHOR]

Introduction: Disseminated carcinomatosis of the bone marrow is caused by cancer metastasis to the bone marrow and is the diagnosis is very difficult by imaging. Case Presentation: We report a 75-year-old male with disseminated carcinomatosis of the bone marrow from castration-resistant prostate cancer revealed by 11C-choline positron emission tomography-computed tomography (PET/CT). Although he already received radiotherapy to the prostate, combined androgen blockade, enzalutamide and apalutamide, and external beam radiotherapy for the pelvic bone metastases, serum prostate-specific antigen (PSA) value rapidly increased from 32 ng/mL to 104 ng/mL in recent 1 month. Bone scintigraphy showed almost no abnormal uptake in the whole body, whereas 11C-choline PET/CT showed diffuse bone marrow 11C-choline uptake. The disseminated carcinomatosis of the bone marrow was diagnosed from the discordant findings between bone scintigraphy and 11C-choline PET/CT examinations and confirmed pathologically by iliac marrow biopsy pathologically. Although docetaxel therapy was started, PSA value continued rising and he died after 4 months of the diagnosis. Conclusion: The discordant findings of choline PET/CT and bone scintigraphy can diagnose disseminated carcinomatosis of the bone marrow from prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the utility of uroflowmetry in predicting anatomical success following urethroplasty based on real‐world clinical data. Methods: Data from 100 male patients who underwent urethroplasty for urethral strictures at our institute were analyzed. Postoperative anatomical success was determined as the passage of a 16.2 Fr flexible endoscope after approximately 4 months following the procedure. Sensitivity and specificity of the maximal flow rate (Qmax), average flow rate (Qave), and Qmax − Qave for anatomical success were determined, along with receiver operating characteristic analysis. The optimal cutoff was set using Youden's index. Results: Anatomical success was observed in 67%. Voided volumes in the success and failure groups were equivalent: 252 ± 121 versus 242 ± 91 ml, respectively. In 18 cases, voided volumes were <150 ml. Parameters of uroflowmetry were all significantly higher in the anatomical success group when compared to those in the failure group: the mean value of Qmax was 26.1 versus 15.0 ml/s; Qave, 14.2 versus 9.1 ml/s; and Qmax − Qave, 11.9 versus 5.9 ml/s, respectively (p < 0.0001 for each parameter). The area under the curve was 0.8082 for Qmax, 0.7727 for Qave, and 0.8186 for Qmax − Qave. Optimal cutoff values for Qmax and Qmax − Qave were 20 and 6 ml/s, which predicted anatomical success with 86% and 87% positive predictive value, respectively. Conclusion: This analysis presents statistically valid cutoffs by which uroflowmetry can be used as a viable surrogate of anatomical success following urethroplasty in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: The utility of 11C‐choline positron emission tomography/computed tomography for determining treatment response as compared with prostate‐specific antigen response and prognosis prediction in castration‐resistant prostate cancer patients was investigated. Methods: Eighty‐four 11C‐choline‐positron emission tomography/computed tomography scans before/after treatments with abiraterone (n = 12 patients), enzalutamide (n = 3), docetaxel (n = 9), cabazitaxel (n = 5), radiation therapy alone (n = 3), radiation therapy, enzalutamide, and/or abiraterone (n = 5), radium‐223 (n = 4), and radiofrequency ablation (n = 1) in 42 castration‐resistant prostate cancer patients were retrospectively examined. Prostate‐specific antigen values were determined before and after treatment. Using the Kaplan–Meier method, the correlation of Positron Emission Tomography Response Criteria In Solid Tumors with prostate‐specific antigen response and prognostic impact was evaluated. Results: Pretreatment 11C‐choline‐positron emission tomography/computed tomography findings identified local, lymph node, bone, and visceral metastasis in 12, 12, 29, and five patients, respectively. Following treatments, complete metabolic response was noted in one, partial metabolic response in eight, stable metabolic disease in 13, and progressive metabolic disease in 20. Mean prostate‐specific antigen change for complete metabolic response, partial metabolic response, stable metabolic disease and progressive metabolic disease was −48.9%, −55.0% (range −92.4% to −19.1%), −4.2% (−33.2% to 35.1%), and 142.7% (30.7% to 373.8%), respectively, significantly greater in the progressive metabolic disease cases (P < 0.01). Positron Emission Tomography Response Criteria In Solid Tumors was well correlated with prostate‐specific antigen change. Patients with no progression (complete metabolic response/partial metabolic response/stable metabolic disease) showed significantly longer cancer‐specific survival than progressive metabolic disease (P < 0.005). Using pretreatment 11C‐choline‐positron emission tomography/computed tomography results to divide into three groups; (a) local and/or lymph node metastasis without bone metastasis (n = 10), (b) <6 bone metastasis sites (n = 16), (c) ≥6 bone metastasis sites and/or visceral metastasis (n = 16), cancer‐specific survival showed significant stratification (P < 0.001). Conclusions: 11C‐choline‐positron emission tomography/computed tomography may reflect castration‐resistant prostate cancer metastatic lesion activity for treatment response and prognosis evaluations. [ABSTRACT FROM AUTHOR]

Malfunction of the circadian clock has been linked to the pathogenesis of a variety of diseases. We show that mice lacking the core clock components Cryptochrome-1 (Cry1) and Cryptochrome-2 (Cry2) (Cry-null mice) show salt-sensitive hypertension due to abnormally high synthesis of the mineralocorticoid aldosterone by the adrenal gland. An extensive search for the underlying cause led us to identify type VI 3β-hydroxyl-steroid dehydrogenase (Hsd3b6) as a new hypertension risk factor in mice. Hsd3b6 is expressed exclusively in aldosterone-producing cells and is under transcriptional control of the circadian clock. In Cry-null mice, Hsd3b6 messenger RNA and protein levels are constitutively high, leading to a marked increase in 3(3- hydroxysteroid dehydrogenase-isomerase (3β-HSD) enzymatic activity and, as a consequence, enhanced aldosterone production. These data place Hsd3b6 in a pivotal position through which circadian clock malfunction is coupled to the development of hypertension. Translation of these findings to humans will require clinical examination of human HSD3B1 gene, which we found to be functionally similar to mouse Hsd3b6., Hypertension is a complex trait, influenced by multiple genetic and environmental factors (1). Although it has been estimated that approximately 30-50% of blood pressure variance is due to inherited genes, [...]

Overactive bladder is a highly prevalent clinical condition that is often caused by bladder outlet obstruction (BOO). Increased coupling of bladder smooth muscle cells (BSMC) via gap junctions has been hypothesized as a mechanism for myogenic bladder overactivity in BOO, although little is known about the regulatory system underlying such changes. Here, we report the involvement of basic fibroblast growth factor (bFGF) and connexin 43, a bladder gap junction protein, in bladder overactivity. BOO created by urethral constriction in rats resulted in elevated bFGF and connexin 43 levels in the bladder urothelium and muscle layer, respectively, and muscle strips from these bladders were more sensitive than those from sham-operated controls to a cholinergic agonist. In vitro bFGF treatment increased connexin 43 expression in cultured rat BSMC via the ERK 1/2 pathway. This finding was supported by another in vivo model, where bFGF released from gelatin hydrogels fixed on rat bladder walls caused connexin 43 upregulation and gap junction formation in the muscle layer. Bladder muscle strips in this model showed increased sensitivity to a cholinergic agonist that was blocked by inhibition of gap junction function with [alpha]-glycyrrhetinic acid. Cystometric analyses of this model showed typical features of detrusor overactivity such as significantly increased micturition frequency and decreased bladder capacity. These findings suggest that bFGF from the urothelium could induce bladder hypersensitivity to acetylcholine via gap junction generation in the smooth muscle, thereby contributing to the myogenic overactivity of obstructed bladders. bFGF; bladder smooth muscle cell; connexin 43; ERK; hypersensitivity

Bladder hypertrophy is a general consequence of bladder outlet obstruction (BOO) and a typical phenomenon observed in clinical urologic diseases such as benign prostatic hyperplasia and neurogenic bladder. It is characterized by smooth muscle hyperplasia, altered extracellular matrix composition, and increased contractile function. Various growth factors are likely involved in hypertrophic pathophysiology, but their functions remain unknown. In this report, the role of basic fibroblast growth factor (bFGF) was investigated using a rat bladder smooth muscle cell (BSMC) culture system and an original animal model, in which bFGF was released from a gelatin hydrogel directly onto rat bladders, bFGF treatment promoted BSMC proliferation both in vitro and in vivo. In vitro, bFGF downregulated the expression of type I collagen, but upregulated type III collagen. ERK1/2, but not p38MAPK, was activated by bFGF, whereas inhibition of ERK1/2 by PD98059 reversed bFGF-induced BSMC proliferation, type I collagen downregulation, and type III collagen upregulation. In the in vivo release model, bFGF upregulated type III collagen and increased the contractile force of treated bladders. In parallel with these findings, hypertrophied rat bladders created by urethral constriction showed increased urothelial bFGF expression, BSMC proliferation, and increased type III collagen expression compared with sham-operated rats. These data suggest that bFGF from the urothelium could act as a paracrine signal that stimulates the proliferation and matrix production of BSMC, thereby contributing to the hypertrophic remodeling of the smooth muscle layer. bFGF; bladder smooth muscle cell; type I collagen; type III collagen; ERK

Hollow organs exposed to pathological stimuli undergo phenotypic modulation characterized by altered expression of smooth muscle contractile proteins and loss of normal function. The molecular mechanisms that regulate smooth muscle differentiation, especially in organs other than the vasculature, are poorly understood. In this study, we describe a role for the GATA-6 transcription factor in regulation of human bladder smooth muscle differentiation. Knockdown of endogenous GATA-6 in primary human bladder smooth muscle cells (pBSMC) led to decreased mRNA levels of the differentiation markers [alpha]-smooth muscle actin ([alpha]-SMA), calponin, and smooth muscle myosin heavy chain. Similar effects were obtained following downregulation of GATA-6 by forskolin-induced elevation of intracellular cAMP levels. Forskolin treatment of pBSMC abolished recruitment of GATA-6 to the [alpha]-SMA promoter in vivo and reduced activity of human [alpha]-SMA promoter-directed gene expression by >60%. This inhibitory effect was rescued by enforced expression of wild-type GATA-6 but not by a zinc-finger-deleted mutant, GATA-6-[DELTA]ZF, which lacks DNA-binding ability. In silico analysis of a region of the human [alpha]-SMA promoter, described previously as a transcriptional enhancer, identified a putative GATA-binding site at position -919/ -913. Point mutation of this site in SMA-Luc abrogated GATA-6induced activation of promoter activity. Together, these results provide the first evidence for a functional role for GATA-6 in regulation of bladder smooth muscle differentiation. In addition, these findings demonstrate that GATA-6 regulates human [alpha]-SMA expression via a novel regulatory cis element in the [alpha]-SMA promoter-enhancer. hollow organs; contractile proteins; dedifferentiation; adenosine 3',5'-cyclic monophosphate