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OBJECTIVES To evaluate the ability of photocurable gelatin to prevent stricture recurrence after urethral dilation in a rabbit urethral stricture model. METHODS We created urethral strictures in the bulbar urethras of 10 male Japanese white rabbits using electrocoagulation. After 1 month, the rabbits were randomly divided into Group A (n = 5; urethral stricture dilation and the local application of photocurable gelatin using a ruthenium photoinitiator and irradiation with a light-emitting diode light [λ = 455 nm, 50 mW/cm2 ] for 1 min) and Group B (n = 5; dilation only). Urethral stricture status was evaluated 1-2 months later by retrograde urethrography and urethroscopy. The lumen ratio (urethral width at the stricture site to the normal urethral width on retrograde urethrography) was calculated. Urethral patency was considered to be improved when the urethral lumen could accommodate a 10-Fr urethroscope without resistance. Urethral specimens were harvested for histopathological examination. RESULTS The mean lumen ratio did not differ significantly between Groups A and B before dilation (25.8% vs 23.4%; P = 0.40), but differed significantly after dilation (65.5% vs 27.3%, respectively; P = 0.03). Urethral patency improved in all rabbits in Group A (100%) versus one rabbit in Group B (20%; P = 0.02). The mean circumference of the regenerated urethral epithelium at the stricture site was larger in Group A than in Group B (14 mm vs 6.6 mm; P = 0.06). CONCLUSIONS Photocurable gelatin can reduce urethral stricture recurrence after dilation in a rabbit model.

To examine the efficacy of perineal urethrostomy (PU) in patients with anterior urethral stricture. Patients who underwent PU for anterior urethral stricture between 2013 and 2020 were retrospectively reviewed (n = 56). Surgical success was defined as no need for additional intervention. Uroflowmetry and measurement of residual urine volume (PVR) were examined postoperatively, and the patients were asked to fill out sexual health inventory for men (SHIM) and the validated Urethral Stricture Surgery Patient-reported Outcome Measure questionnaires before and after PU. The overall patient satisfaction was also assessed. PU was successful in 92.9% of patients (n = 52), with a median follow-up of 34 months. Two of four were salvaged by re-do PU, and one was salvaged by forming a composite stoma using a penile skin graft. Thirty-nine patients (69.6%) filled out the questionnaires 6 months after surgery. The mean maximum flow rate, PVR, lower urinary tract symptoms (LUTS)-total score, LUTS-specific quality of life, and EuroQol-visual analog scale scores improved significantly from 3.8 mL/s, 77.6 mL, 12.9, 2.6, and 53.6 at baseline to 17.6 mL/s, 21.3 mL, 4.1, 0.9, and 74.9 postoperatively (p = 0.003, p = 0.004, p = 0.005, p

Objectives Up to 0.3% of Japanese have hypouricaemia. Most cases appear to result from a hereditary disease, renal hypouricaemia (RHUC), which causes exercise-induced acute kidney injury and urolithiasis. However, to what extent RHUC accounts for hypouricaemia is not known. We therefore investigated its frequency and evaluated its risks by genotyping a general Japanese population. Methods A cohort of 4993 Japanese was examined by genotyping the non-functional variants R90H (rs121907896) and W258X (rs121907892) of URAT1/SLC22A12, the two most common causative variants of RHUC in Japanese. Results Participants’ fractional excretion of uric acid and risk allele frequencies markedly increased at lower serum uric acid (SUA) levels. Ten participants (0.200%) had an SUA level ≤2.0 mg/dl and nine had R90H or W258X and were likely to have RHUC. Logistic regression analysis revealed these URAT1 variants to be significantly and independently associated with the risk of hypouricaemia and mild hypouricaemia (SUA ≤3.0 mg/dl) as well as sex, age and BMI, but these URAT1 variants were the only risks in the hypouricaemia population (SUA ≤2.0 mg/dl). W258X was only a risk in males with SUA ≤3.0 mg/dl. Conclusion Our study accurately reveals the prevalence of RHUC and provides genetic evidence for its definition (SUA ≤2.0 mg/dl). We also show that individuals with SUA ≤3.0 mg/dl, especially males, are prone to RHUC. Our findings will help to promote a better epidemiological understanding of RHUC as well as more accurate diagnosis, especially in males with mild hypouricaemia.

Objectives To verify the utility of triangular extension of a hinge flap in buccal mucosal staged urethroplasty to resolve stomal stenosis after the first stage and ultimately prevent restenosis. Methods A total of 23 patients (triangular extension group) were studied in 2013-2019. In the first stage, buccal mucosa was transplanted, and an extended triangle portion of the mucosa was placed beside the proximal and/or distal stoma that was created when the stricture segment of the urethra was resected. In the second stage, during tubularization of the urethral plate, an incision was made at the stoma to increase the caliber to which the triangular extension was inserted. The procedure was considered successful when a 17-Fr flexible cystoscope passed through the reconstructed urethra at 6 months after the second-stage urethroplasty and no additional surgery or bougie dilation required. The clinical course of the triangular extension group was compared with 24 patients who underwent conventional staged urethroplasty (control group). Results In total, 20 patients from each group underwent second-stage surgery. No patients in the triangular extension group required additional revision surgery because of stomal stenosis after first-stage surgery, whereas five (20%) control patients did. Urethroplasty was successful in 19 patients (95%) in the triangular extension group and in 19 patients (95%) in the control group. Uroflowmetry after the second-stage surgery indicated that the mean maximum urinary flow rate was 21.5 and 15.8 mL/s after triangular extension and the control procedure, respectively (P = 0.027). Conclusions The triangular extension technique reduces the need for revision surgery and prevents postoperative restenosis.

Objective Immediate single instillation of chemotherapy following transurethral resection of bladder tumor (TURBT) is suggested for non-muscle invasive bladder cancer (NMIBC) patients. However, no study has evaluated molecular marker that was involved in intravesical recurrence (IVR) after single instillation of chemotherapy. Therefore, this study aimed to evaluate whether P-glycoprotein, multidrug resistance protein 1 (MRP1), Annexin A2 (ANXA2) or nucleophosmin (NPM) expression predicts IVR after initial TURBT and immediate single intravesical adriamycin instillation. Methods We retrospectively reviewed consecutive 443 patients who underwent TURBT. Of these, 54 patients who underwent initial TURBT and single instillation of adriamycin for NMIBC were included. The expressions of P-glycoprotein, MRP1, ANXA2 and NPM were evaluated immunohistochemically and were divided into 2 groups (low or high) according to the staining intensity and/or proportion of positive cells. IVR was assessed by Kaplan-Meier method. Cox`s multivaritate analyses were performed to identify independent predictors for IVR. Results Nineteen patients (35.1%) had IVR. High P-glycoprotein expression was significantly correlated with multiplicity, pT stage and high grade. High ANXA2 expression was significantly correlated with high grade. MRP1 and NPM were not correlated with any clinicopathological variables. MRP1 expression and ANXA2 expression were significantly correlated with P-glycoprotein expression. Patients with high P-glycoprotein expression had significantly worse IVR-free survival (IVRFS) than those with low P-glycoprotein expression (P =0.015). The difference in IVRFS rates between patients with high ANXA2 expression and those with low ANXA2 expression was nearly significant (P =0.057). Univariate analyses indicated multiplicity, high grade and high P-glycoprotein expression were significant predictors for IVR. Multivariate analysis indicated high grade was an independent predictor for IVR. Conclusions High P-glycoprotein expression was associated with IVR. Further study was needed to determine significance of P-glycoprotein expression in IVR after single intravesical adriamycin instillation.

OBJECTIVES To evaluate whether the management of anterior urethral strictures prior to definitive urethroplasty is appropriate. METHODS Of a total of 419 men diagnosed with anterior urethral strictures at hospitals across Japan and thereafter referred to our institution for definitive urethroplasty between 2004 and 2019, the medical records of 371, for whom data on stricture characteristics at the initial diagnosis and pre-referral management were available, were retrospectively reviewed. A pre-referral single transurethral procedure, such as direct vision internal urethrotomy or urethral dilation, was considered appropriate only for favorable stricture, defined as a single nontraumatic untreated bulbar urethral stricture ≤2 cm in size, and repeat transurethral procedures were considered inappropriate in any circumstances. The association between the appropriateness of the pre-referral management strategy and patient and clinical characteristics was analyzed. RESULTS A total of 242 patients (65.2%) had a pre-referral history of at least one transurethral procedure, and performing the procedure was considered inappropriate for 221 patients (59.6%). On multivariate logistic regression analysis, location of the patient's residence far from our institution (outside of the Kanto area; odds ratio 3.35, 95% confidence interval 1.86-6.04; P

OBJECTIVES Pubectomy is an ancillary technique used to increase exposure of the disrupted urethra and reduce anastomotic tension, which can be difficult for inexperienced surgeons. The objective of the present study was to illustrate the use of an air drill enabling delicate and precise bone resection in pubectomy for delayed anastomotic urethroplasty for pelvic fracture urethral injury. METHODS Between 2009 and 2019, 88 male patients underwent delayed anastomotic urethroplasty with pubectomy for pelvic fracture urethral injury. A total of 73 procedures used a high-speed surgical air drill (HiLAN HS; Aesculap, Tuttlingen, Germany) equipped with a short-hand piece. Operative time and blood loss in the air drill patient group (group 1) were compared with that of patients who underwent pubectomy using a rongeur and/or gouge (group 2, n = 15). RESULTS In 65 group 1 patients, urethroplasty was carried out using the perineal approach, with partial inferior pubectomy. Eight group 1 patients, whose proximal urethral end was displaced upward superior to the upper edge of pubis, underwent urethroplasty using the perineal and abdominal approach, with a superior partial pubectomy and supracrural urethral rerouting. No difficulty was encountered using the air drill in any of the cases. There was no significant difference in median operative time between the groups (group 1 256 min vs group 2 228 min; P = 0.31). The median blood loss in group 1 was significantly lower than group 2 (149 mL vs 453 mL; P

Objectives To evaluate the magnetic resonance imaging (MRI) findings of traumatic bulbar stricture and to evaluate their ability to estimate repair complexity. Methods Eighty-nine men with traumatic bulbar stricture who underwent urethrography and MRI at least 3 months post-injury and subsequent excision and primary anastomosis were retrospectively analyzed. The associations of MRI findings, including continuity of the tunica albuginea of the corpus spongiosum, periurethral fistula, spongiofibrosis length (SFL), and distal and proximal bulbar urethral length (PBL) from the stricture, with urethrography and operative parameters were evaluated. Results Mean SFL was significantly longer than mean stricture length on urethrography (14.9 vs. 7.9 mm, p Conclusions In contrast to urethrography findings, MRI findings help predict traumatic bulbar stricture repair complexity.

A supercontinuum (SC) light source enables multispectral photoacoustic imaging at excitation wavelengths in the visible-to-near-infrared range. However, for such a broad optical wavelength range, chromatic aberration is non-negligible. We developed a multispectral optical-resolution photoacoustic microscopy (MS-OR-PAM) setup with a nanosecond pulsed SC light source and a reflective objective lens to avoid chromatic aberration. Chromatic aberrations generated by reflective and conventional objective lenses were compared, and the images acquired using the reflective objective were not affected by chromatic aberration. Hence, MS-OR-PAM with the reflective objective was used to distinguish red blood cells from melanoma cells via spectral subtraction processing.

Surgical resection is the standard treatment for the management of localized penile cancer and a neo-urethral meatus is generally created on the penile stump or perineum. Neo-urethral meatus is often stenosed and requires repeated transurethral manipulations such as dilation and urethrotomy. These procedures are generally futile and are associated with poor quality of life. Here, we report a case of penile cancer that developed a neo-meatal stenosis after total penectomy, which was subsequently salvaged by perineal urethrostomy using Blandy technique. A 72-year-old male who was diagnosed with localized penile cancer, underwent total penectomy and creation of neo-meatus on the perineum. Neo-meatus stenosis had developed in the patient and he received repeated urethral dilations without any success. Finally, when the patient was unable to void, he was referred to us for the amelioration of meatal stenosis through the placement of a suprapubic catheter. Because the condition of the residual bulbar urethra was adequate and its length was enough, we planned to create a non-transecting perineal urethrostomy by Blandy technique. An inverted U-shaped perineal incision was made, and a skin flap was created. The scarred neo-meatus and spongiofibrosis at the distal bulbar urethra were completely excised. The residual bulbar urethra was exposed, and a longitudinal ventral incision of 4 cm was made. The edge of the bare urethral mucosa and tunica albuginea of the corpus spongiosum were sutured by 4-0 PDS for hemostasis. The apex of the U-shaped skin flap was brought to the proximal margin of the urethrotomy and a tension-free anastomosis was created between the skin flap and the urethral plate. Thereafter, the skin of the perineum was sutured to the open longitudinal urethrotomy. The patient started to void on the 5th day post-surgery. The subject could void without the help of any intervention and did not require any instrument, sixteen weeks after the surgery.

Objective Accumulating evidence indicates that high uric acid (UA) is strongly associated with obesity and metabolic syndrome and drives the development of nonalcoholic fatty liver disease (NAFLD) and insulin resistance. Although urate transporter-1 (URAT1), which is primarily expressed in the kidneys, plays a critical role in the development of hyperuricemia, its pathophysiological implication in NAFLD and insulin resistance remains unclear. We herein investigated the role and functional significance of URAT1 in diet-induced obese mice. Methods Mice fed a high-fat diet (HFD) for 16–18 weeks or a normal-fat diet (NFD) were treated with or without a novel oral URAT1-selective inhibitor (dotinurad [50 mg/kg/day]) for another 4 weeks. Results We found that URAT1 was also expressed in the liver and brown adipose tissue (BAT) other than the kidneys. Dotinurad administration significantly ameliorated HFD-induced obesity and insulin resistance. HFD markedly induced NAFLD, which was characterized by severe hepatic steatosis as well as the elevation of serum ALT activity and tissue inflammatory cytokine genes (chemokine ligand 2 (Ccl2) and tissue necrosis factor α (TNFα)), all of which were attenuated by dotinurad. Similarly, HFD significantly increased URAT1 expression in BAT, resulting in lipid accumulation (whitening of BAT), and increased the production of tissue reactive oxygen species (ROS), which were reduced by dotinurad via UCP1 activation. Conclusions In conclusion, a novel URAT1-selective inhibitor, dotinurad, ameliorates insulin resistance by attenuating hepatic steatosis and promoting rebrowning of lipid-rich BAT in HFD-induced obese mice. URAT1 serves as a key regulator of the pathophysiology of metabolic syndrome and may be a new therapeutic target for insulin-resistant individuals, particularly those with concomitant NAFLD., Graphical abstract Vicious cycle of URAT1 activity and insulin resistance in the pathophysiology of metabolic syndrome. The impacts of URAT1 is amplified in metabolic syndrome via persistent exposure to hyperinsulinemia. Conversely, enhanced URAT1 action induces insulin resistance in metabolic syndrome, leading to a vicious cycle. URAT1-selective inhibitor may be particularly effective in reducing hyperuricemia associated with insulin-resistant metabolic disorders by severing this vicious cycle.Image 1, Highlights • URAT1 is expressed in the liver and brown adipose tissue other than in the kidneys. • URAT1-selective inhibitor ameliorates HFD-induced insulin resistance. • URAT1-selective inhibitor improves NAFLD through the inhibition of Ccl2 and TNFα. • URAT1-selective inhibitor promotes rebrowning of HFD-induced lipid-rich BAT. • URAT1 serves as a key regulator of the pathophysiology of metabolic syndrome.

OBJECTIVES To investigate the incidence of overactive bladder in men with anterior urethral stricture and to evaluate the impact of urethroplasty on its improvement. METHODS A total of 104 men with anterior urethral stricture who underwent urethroplasty between 2016 and 2020 completed a validated urethral stricture surgery patient-reported outcome measure comprising six lower urinary tract symptoms questions on voiding symptoms and overactive bladder symptom score before and 3, 6, and 12 months after urethroplasty. Patients with an urgency score of ≥2 for overactive bladder symptom score question 3, and a total overactive bladder symptom score of ≥3 were considered to have overactive bladder. An improvement in overactive bladder was defined as a decrease in the total overactive bladder symptom score by at least three points. RESULTS Thirty-nine patients (37.5%) were considered to have overactive bladder, and improvement in overactive bladder after urethroplasty was found in 30 (76.9%). Maximum flow rate on uroflowmetry, postvoid residual urine volume, lower urinary tract symptoms total score, and total overactive bladder symptom score were all significantly improved after urethroplasty (P

We studied the impact of membranous urethral length (MUL) on magnetic resonance imaging (MRI) on post-urethroplasty continence in male patients with pelvic fracture urethral injury (PFUI). Of 169 male patients with PFUI who underwent delayed anastomotic urethroplasty between 2008 and 2020, 85 who underwent preoperative MRI, had no recurrent stenosis on cystoscopy, and underwent a 1-h pad test 1 year after surgery were included. MUL was defined as the distance from the distal end of the disrupted proximal urethra to the apex of the prostate, as measured using T2-weighted MRI. Urinary incontinence (UI) was defined as a 1-h pad test weight > 2.0 g. None of the patients had UI before a pelvic fracture. Eighty-two patients (96.5%) had a measurable MUL, and the median length was 8.1 (interquartile range [IQR], 5.2–10.8) mm. The median weight of the 1-h pad test was 1.0 (IQR, 0.0–4.0) g, and 26 (30.6%) patients had UI. An open bladder neck (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.0–22.0; p = 0.04) and a short measurable membranous urethra (for every extra mm: OR, 1.2; 95% CI, 1.0–1.3; p = 0.04) were significant UI predictors on multivariate analysis. A long MUL is significantly positively associated with urinary continence in male patients with PFUI. This could be of potential value to reconstructive urologists when counseling patients regarding post-urethroplasty continence before urethroplasty.

Introduction Two percent of testicular germ cell tumors occur in family clusters. Here, we report metachronous testicular germ cell tumors in two brothers. Case presentation An elder brother was diagnosed at the age of 30 years old and the pathological diagnosis was mixed testicular germ cell tumor. A tumor in the younger brother was suspected during testicular self-examination. It was confirmed by ultrasound examination at the age of 30 years old, 3 years and 6 months after the diagnosis of the testicular tumor in elder brother. The pathological diagnosis was pure seminoma. Both brothers had stage 1 testicular germ cell tumors and no recurrence was observed during the follow-up period of 4 years and 4 months and 10 months, respectively. Conclusion Various histological types of tumor can occur in members of one family. Besides genetic predisposition, shared diet, environmental exposure and other factors can contribute to the familial testicular cancer. Testicular self-examination is recommended for family members of a person with testicular germ cell tumor.

To report our experience with urethroplasty for bulbar stricture due to a straddle injury based on surgical and patient-reported outcomes. Patients who underwent urethroplasty for bulbar stricture due to a straddle injury between 2010 and 2018 were retrospectively analyzed (N = 132). Successful urethroplasty was defined as the absence of the need for additional treatment. The patients completed the validated Urethral Stricture Surgery Patient-reported Outcome Measure and Sexual Health Inventory for Men (SHIM) questionnaires before (baseline) and 1 year after urethroplasty. The median (interquartile range) age was 50 (36–62) years; urethral stricture length estimated from urethrograms, 8.6 (5.1–12.5) mm; and postoperative follow-up, 41 (22–56) months. Urethroplasty was performed through excision with primary anastomosis in 95.5% (n = 126) and onlay augmentation with a buccal mucosa graft in 4.5% (n = 6). Urethroplasty was successful in 98.5% (n = 130). The 2 failures due to periurethral abscess were successfully salvaged with another urethroplasty. Eighty-four patients (63.6%) completed the questionnaires at 1 year postoperatively. The mean lower urinary tract (LUT)-specific quality of life, SHIM, and EuroQol-visual analog scale scores all improved significantly from 2.6, 8.5, and 57.5 at baseline to 0.3, 11.6, and 84.6 postoperatively (p

Background Recent large-scale clinical trials have shown that SGLT2-inhibitors reduce cardiovascular events in diabetic patients. However, the regulation and functional role of cardiac sodium–glucose cotransporter (SGLT1 is the dominant isoform) compared with those of other glucose transporters (insulin-dependent GLUT4 is the major isoform) remain incompletely understood. Given that glucose is an important preferential substrate for myocardial energy metabolism under conditions of ischemia–reperfusion injury (IRI), we hypothesized that SGLT1 contributes to cardioprotection during the acute phase of IRI via enhanced glucose transport, particularly in insulin-resistant phenotypes. Methods and results The hearts from mice fed a high-fat diet (HFD) for 12 weeks or a normal-fat diet (NFD) were perfused with either the non-selective SGLT-inhibitor phlorizin or selective SGLT2-inhibitors (tofogliflozin, ipragliflozin, canagliflozin) during IRI using Langendorff model. After ischemia–reperfusion, HFD impaired left ventricular developed pressure (LVDP) recovery compared with the findings in NFD. Although phlorizin-perfusion impaired LVDP recovery in NFD, a further impaired LVDP recovery and a dramatically increased infarct size were observed in HFD with phlorizin-perfusion. Meanwhile, none of the SGLT2-inhibitors significantly affected cardiac function or myocardial injury after ischemia–reperfusion under either diet condition. The plasma membrane expression of GLUT4 was significantly increased after IRI in NFD but was substantially attenuated in HFD, the latter of which was associated with a significant reduction in myocardial glucose uptake. In contrast, SGLT1 expression at the plasma membrane remained constant during IRI, regardless of the diet condition, whereas SGLT2 was not detected in the hearts of any mice. Of note, phlorizin considerably reduced myocardial glucose uptake after IRI, particularly in HFD. Conclusions Cardiac SGLT1 but not SGLT2 plays a compensatory protective role during the acute phase of IRI via enhanced glucose uptake, particularly under insulin-resistant conditions, in which IRI-induced GLUT4 upregulation is compromised. Electronic supplementary material The online version of this article (10.1186/s12933-019-0889-y) contains supplementary material, which is available to authorized users.

Background International Metastatic Renal Cell Carcinoma Database Consortium model predicts the outcomes of metastatic renal cell carcinoma stratified into favorable, intermediate, and poor risk groups (FG, IG, and PG, respectively), with approximately 50% of patients being classified as IG. We aimed to generate better risk model based on the sub-classification of IG. Methods We analyzed records of 213 consecutive patients receiving molecular targeted therapy. Age, gender, histology, type of initial molecular targeted therapy, serum laboratory data, previous nephrectomy and immunotherapy, and metastatic sites were used for IG sub-stratification. Modified and original models were compared using a concordance correlation coefficient analysis. Results Median follow-up was 17.8 months. Serum albumin, serum C-reactive protein, and bone metastases were independent predictors of overall survival (OS) in IG. IG was sub-classified into low-, middle-, and high-risk IG according to the number of predictors. The following modified model was developed: modified FG (FG & low-risk IG), modified IG (middle-risk IG), and modified PG (PG & high-risk IG). Concordance indices for original and modified models were 0.68 and 0.73, respectively (P < 0.001). OS was significantly longer in modified PG treated with mammalian target of rapamycin inhibitors as second-line therapy than with tyrosine kinase inhibitors, whereas this was not observed in the original model. Conclusions We successfully developed modified IMDC model using a two-step process: the original IMDC plus an IG sub-stratification, and demonstrated that it predicts outcomes more accurately than original model.

To report our experience with delayed anastomotic urethroplasty for pelvic fracture urethral injury (PFUI) during the last 10 years and evaluate both surgical and patient-reported outcomes. Retrospective analysis of 115 patients undergoing delayed anastomotic urethroplasty for PFUI between 2008 and 2017 by a single surgeon (AH) was performed. Success was defined as a urethral lumen large enough for passage of a 17-Fr flexible cystoscope. We asked patients to complete questionnaires before (baseline) and 1 year after urethroplasty and compared by paired t and Wilcoxon signed-rank tests the answers to a question about LUTS-specific QOL and the health-related QOL indicated by EQ-5D index and visual analogue scores (EQVAS). Overall patient satisfaction 1 year after urethroplasty was also evaluated. Urethroplasty was successful in 108 patients (93.9%), and failed urethroplasty was significantly associated with greater intraoperative blood loss (p = 0.009) and smaller surgical experience (p = 0.018). Sixty-six patients (57.4%) completed questionnaires 1 year after urethroplasty, and 65 of those 66 (98.5%) were “satisfied” (36.4%) or “very satisfied” (62.1%) with the outcome of their urethroplasty. The LUTS-specific QOL scores (p

Background Standard treatments have not been established in metastatic papillary renal-cell carcinoma (PRCC). We aimed to investigate treatment outcomes in patients with mPRCC. Patients and Methods This study included 51 patients who were diagnosed with PRCC at 14 institutions. Pathologic slides were reviewed by pathologists. The associations between clinical factors and overall survival (OS) were analyzed. Results Final pathologic diagnoses could be determined in 50 patients. Thirty-five tumors were diagnosed as PRCC (type 2 PRCC, 91.4%), and 15 were diagnosed as other histologic types. Targeted therapies (TTs) were provided to 25 mPRCC patients. Patients treated with TT survived significantly longer than those treated before the era of TT (median OS, 22.5 vs. 6.3 months; P = .0035). Median OS of patients who experienced stable disease for ≥ 9 months using single TT was 43.1 months. Patients treated with a tyrosine kinase inhibitor (TKI) as first-line TT survived longer after TT initiation than those treated with an mTOR inhibitor (median, 22.4 vs. 11.7 months; P = .2684). Patients treated with TKIs in both first- and second-line settings had significantly better survival after TT initiation than those treated with a TKI in one therapy line and an mTOR inhibitor in the other (31.4 vs. 12.9 months, P = .0172). Patients treated with a TKI as second-line TT survived significantly longer after second-line TT initiation than did those treated with an mTOR inhibitor (16.2 vs. 7.4 months, P = .0016). Conclusion Prognoses of patients with mPRCC were improved by TT, and TKIs appeared to be the treatment of choice in both the first- and second-line settings.

Objectives To investigate the outcomes of deep lateral incision for vesicourethral anastomotic stenosis after radical prostatectomy and its impact on postoperative urinary incontinence. Methods We retrospectively investigated 43 men who underwent deep lateral incision for non-obliterated vesicourethral anastomotic stenosis after radical prostatectomy between 2011 and 2020. The bladder neck was deeply incised through its circular fibers into the surrounding perivesical fat at 3 and 9 o'clock through electrocautery incision using needle-type electrodes. Successful deep lateral incision was defined as the absence of additional treatment, including self-dilatation. The postoperative urinary incontinence status was evaluated based on the number of pads used daily. Results Deep lateral incision was successful in 35 (81.4%) patients, with a median follow-up period of 43 months (interquartile range 15-80 months). There was no significant association of age (P = 0.66), body mass index (P = 0.49) and history of diabetes mellitus (P = 0.39), radiation therapy (P = 0.89) or previous vesicourethral anastomotic stenosis treatment (P = 0.71) with the incision outcomes; however, there were significantly more unsuccessful cases in those with preoperative urinary retention (P = 0.04) or indwelling urinary catheters for >5 days post-incision (P = 0.01). A second incision was carried out in eight patients and a third incision in two patients, resulting in 42 (97.7%) successful incisions. A total of 37 (88.1%) patients had urinary incontinence and used at least one pad daily; seven (16.7%) underwent artificial urinary sphincter implantation after the last incision. Conclusions Deep lateral incision is highly effective for treating vesicourethral anastomotic stenosis after radical prostatectomy. Appropriate treatment is required for urinary incontinence, which occurs frequently after incision.

It has been previously indicated that preoperative plasma fibrinogen levels can correlate with cancer progression and be used as a useful predictor of lymph node metastasis or its premetastatic status such as lymphovascular invasion (LVI). In the present study, how preoperative plasma fibrinogen levels, considered in conjunction with other clinicopathological factors, can predict the presence of LVI and prognosisin patients with upper urinary tract urothelial carcinoma (UTUC) was examined. Medical records of 145 patients with UTUC who underwent radical nephroureterectomy (RNU) were retrospectively reviewed. The current study evaluated systemic inflammatory response markers including levels of plasma fibrinogen and other clinicopathological factors in orderto determine independent predictors of LVI and prognosis. The Cox proportional hazards model indicated that positive surgical margins and LVI were independent factors for poor cancer-specific survival (CSS) rates and extraurothelial recurrence-free survival (ERFS) rates. In addition, positive cytology, the presence of hydronephrosis and plasma fibrinogen levels were significant preoperative predictors of LVI. Furthermore, patients exhibiting two or more of higher fibrinogen levels (≥400 mg/dl), positive urine cytology and the presence of hydronephrosis were indicated to exhibit worse CSS or ERFS rates compared with patients exhibiting only one of the aforementioned factors or those with none of the three aforementioned factors in the multivariate analysis of the Cox proportional hazards model. In conclusion, hyperfibrinogenemia can be an independent predictor of the presence of LVI, and stratifying preoperative risk using fibrinogen levels, urine cytology and hydronephrosis can serve as the basis for selecting candidates for additional therapy before and/or after RNU in patients with UTUC.

Image preprocessing is an important process during pattern recognition which increases the recognition performance. Linear convolution filtering is a primary preprocessing method used to enhance particular local patterns of the image which are essential for recognizing the images. However, because of the vast search space of the preprocessing filter, almost no earlier studies have tackled the problem of identifying an optimal preprocessing filter that yields effective features for input images. This paper proposes a novel design method for the optimal preprocessing filter corresponding to a given task. Our method calculates local image bases of the training dataset and represents the optimal filter as a linear combination of these local image bases with the optimized coefficients to maximize the expected generalization performance. Thereby, the optimization problem of the preprocessing filter is converted to a lower-dimensional optimization problem. Our proposed method combined with a higher-order local auto-correlation (HLAC) feature extraction exhibited the best performance both in the anomaly detection task with the conventional pattern recognition algorithm and in the classification task using the deep convolutional neural network compared with typical preprocessing filters.

OBJECTIVES To investigate the efficacy of re-do urethroplasty for post-traumatic urethral stricture in terms of anatomical and functional outcomes. METHODS A total of 48 patients who underwent re-do urethroplasty for post-traumatic urethral stricture due to perineal trauma (n = 21) and pelvic fracture urethral injury (n = 27) between October 2010 and March 2020 were retrospectively reviewed. Patients were followed by uroflowmetry, post-void residual volume assessment and 17-Fr flexible cystoscopy after re-do urethroplasty. Successful urethroplasty was defined as having a urethral caliber adequate for the passage of a cystoscope and requiring no additional treatments. Patients completed a validated patient-reported outcome measure for urethral stricture surgery, including overall satisfaction, and the sexual health inventory for men. RESULTS The type of re-do urethroplasty was anastomotic urethroplasty in 45 (94%) patients and buccal mucosa urethroplasty in three (6%) patients. Urethroplasty was successful in 47 (98%) patients (median follow up 35 months, interquartile range 21-75). The patient-reported outcome measure for urethral stricture surgery and Sexual Health Inventory for Men were assessed in 36 (75%) patients, and the mean lower urinary tract symptom-specific quality of life, EuroQol-5D and EuroQol-visual analog scale scores improved from 2.86, 0.63 and 54.17 preoperatively to 0.78 (P

A very common way to classify bacteria is through microscopic images. Microscopic cell counting is a widely used technique to measure microbial growth. To date, fully automated methodologies are available for accurate and fast measurements; yet for bacteria dividing longitudinally, as in the case of Candidatus Thiosymbion oneisti, its cell count mainly remains manual. The identification of this type of cell division is important because it helps to detect undergoing cellular division from those which are not dividing once the sample is fixed. Our solution automates the classification of longitudinal division by using a machine learning method called residual network. Using transfer learning, we train a binary classification model in fewer epochs compared to the model trained without it. This potentially eliminates most of the manual labor of classifying the type of bacteria cell division. The approach is useful in automatically labeling a certain bacteria division after detecting and segmenting (extracting) individual bacteria images from microscopic images of colonies.

The purpose of the present study was to investigate the prognostic value of the postoperative C-reactive protein/albumin ratio (CAR) in patients with bladder cancer undergoing radial cystectomy. The present study retrospectively reviewed 102 patients who underwent radical cystectomy and were followed for ≥6 months postoperatively at our institution, and evaluated clinicopathological factors and laboratory parameters for cancer-specific survival (CSS) and extraurothelial recurrence-free survival (ERFS). Multivariate analysis using the Cox proportional hazards model revealed that only postoperative CAR ≥0.27 [hazard ratio (HR), 3.368; 95% confidence interval (CI), 1.674-6.731; P

To report our experience with excision and primary anastomosis (EPA) for bulbar urethral stricture. Patients who underwent EPA for bulbar stricture between 2012 and 2019 were retrospectively analyzed (n = 308). Successful urethroplasty was defined as the absence of the need for additional treatment. For follow-up, uroflowmetry was performed and the patients completed the validated Urethral Stricture Surgery Patient-reported Outcome Measure and Sexual Health Inventory for Men (SHIM) questionnaires before (baseline) and 6 months after EPA. Overall patient satisfaction after urethroplasty was also evaluated. Urethroplasty was successful in 97.1% of patients (n = 299) with a median follow-up of 37 months. A total of 215 patients (69.8%) completed the questionnaires at 6 months postoperatively. The mean maximum flow rate, lower urinary tract symptom (LUTS)-total score, Peeling’s picture score, LUTS-specific quality of life, and EuroQol-visual analog scale scores improved significantly from 7.7 ml/s, 11.6, 3.3, 2.4, and 58.0 at baseline to 24.1 ml/s, 2.7, 1.9, 0.4, and 82.1 postoperatively (p

Tumor budding, defined as a single cancer cell or clusters of fewer than five cancer cells observed at the tumor invasion front, has been reported to be associated with poor prognosis in various types of cancers. However, limited information regarding the pathological and prognostic significance of tumor budding in upper urinary tract urothelial carcinoma (UUTUC) is available. We investigated 135 consecutive patients with newly diagnosed invasive UUTUCs (73 with renal pelvic cancers and 62 with ureteral cancers) treated with nephroureterectomy or partial ureterectomy between 1999 and 2018 in our hospital. Under a × 200 magnification, tumors with 10 or more budding foci were defined as “high tumor budding”. The median follow-up period was 53.6 months. Among the 135 patients, 41 (30%; 16 with renal pelvic cancers and 25 with ureteral cancers) showed high tumor budding. High tumor budding was related to adjuvant chemotherapy status, higher pathological T stage, lymphovascular invasion, lymph node metastasis, tumor location, concomitant variant histology, and non-papillary gross finding. The multivariate Cox analysis revealed that LVI and high tumor budding were independent predictors for extraurothelial recurrence (P = 0.039 and 0.014, hazard ratio = 2.50 and 2.88, respectively), and high tumor budding was an independent predictor for overall survival (P = 0.024, hazard ratio = 2.33). Tumor budding can be easily introduced in clinical practice with no need for immunohistochemical analysis, may be an important clinicopathological factor of UUTUC, and is suggested to be useful as a novel predictive prognostic factor of patients with invasive UUTUC.

We report a case of unusually aggressive behavior of a mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney with no sarcomatoid changes. A 43-year-old man was referred to our hospital for a mass on his left kidney. Computed tomography revealed a tumor at the upper pole of the kidney and swollen lymph nodes. Left radical nephrectomy with lymph node dissection was performed and the tumor was diagnosed as MTSCC. Peritoneal dissemination was detected 4 months after the surgery. The patient received systemic treatments, which were not effective. He finally died of the disease 12 months after the surgery.

A single immediate instillation of chemotherapy following transurethral resection of bladder tumor (TURBT) is effective in preventing intravesical recurrence (IVR) in patients with non-muscle-invasive urothelial bladder carcinoma (NMIBC). However, continuous saline bladder irrigation (CSBI) is also performed with a single instillation of chemotherapy (SIC), but its inhibitory effect on IVR remains unclear. In the present study, the effect of CSBI with concomitant SIC following TUR on IVR was evaluated in patients with NMIBC. A retrospective review of 253 patients who underwent TURBT and were clinically and histologically diagnosed with NMIBC at National Defense Medical College Hospital was performed. Doxorubicin (DXR) was administered to all patients. Methods of DXR administration included a single instillation of DXR (60 mg in 30-40 ml saline) in 34 patients (group A), continuous irrigation of the bladder with saline including DXR (80 mg in 1 liter saline) in 40 patients (group B) and overnight CSBI after a single instillation of DXR in 179 patients (group C). The difference in IVR-free survival rates was compared after adjusting for significant differences in several covariates between the groups by nearest-neighbor propensity score matching. Prior to propensity score matching, it was identified that time to IVR was significantly longer in group A than in groups B and C; however, it was observed that several factors significantly differed among the three groups. By using nearest neighbor matching, 18 pairs were matched between groups A and B and 33 pairs between the groups A and C. No significant difference was identified in any covariates between these two matched group pairsTime to IVR was significantly longer in the matched group A than in the matched groups B and C (P=0.0255 and P=0.0023, respectively). In conclusion, SIC alone could provide a higher IVR-free survival rate than CSBI with DXR or CSBI with SIC.

A 46-year-old man underwent right partial nephrectomy for type 2 papillary renal cell carcinoma (PRCC) in 2011. Lung metastasis and lymph node (LN) metastases around the inferior vena cave appeared in 2012. A right radical nephrectomy and extensive LN dissection was performed and the resection of lung metastasis was performed one month after the nephrectomy. Mediastinal LN metastases occurred in 2013, and resection of the affected LNs was performed. Sunitinib and zoledronic acid was started in 2014 because mediastinal LN swelling and multiple bone metastases appeared. Sunitinib treatment was stopped soon after due to adverse events and axitinib treatment was started. Axitinib was effective and the patient had stable disease for 30 months. Adverse events were successfully controlled by dose reduction and periodic drug withdrawal schedules (for example, 5 days on, 2 days off). Axitinib was further continued for 19 months as the metastatic lesions had progressed slowly. Temsirolimus treatment was started in 2019, but it was stopped after three cycles due to interstitial pneumonia. The patient died 80 months after the initial recurrence. Using multidisciplinary treatment, durable disease control was achieved in a patient with metastatic type 2 PRCC.

We report a case of a 53-year-old woman with emphysematous pyelonephritis who presented the preservation of the ipsilateral kidney following open drainage. She was transferred to our hospital with chief complaints of right back pain and high fever. On diagnosis, diabetes mellitus and a stone in the right ureter were confirmed, and she was followed up at a local clinic. Computed tomography revealed the presence of gas in the right renal pelvis, and the stone led to right hydronephrosis. Additionally, her hemoglobin A1c level was 11.3%. Hence, we diagnosed the patient with emphysematous pyelonephritis. Although right percutaneous nephrostomy was performed immediately after her admission, the gas in the right renal pelvis extended to the renal parenchyma one day later. Therefore, we performed open drainage of the right kidney to control severe inflammation. The gas disappeared after the procedure, and her systemic status gradually improved. We hypothesize that emphysematous pyelonephritis is treated with open drainage instead of nephrectomy while preserving the ipsilateral kidney.

In this paper we propose a distributed architecture to provide machine learning practitioners with a set of tools and cloud services that cover the whole machine learning development cycle: ranging from the models creation, training, validation and testing to the models serving as a service, sharing and publication. In such respect, the DEEP-Hybrid-DataCloud framework allows transparent access to existing e-Infrastructures, effectively exploiting distributed resources for the most compute-intensive tasks coming from the machine learning development cycle. Moreover, it provides scientists with a set of Cloud-oriented services to make their models publicly available, by adopting a serverless architecture and a DevOps approach, allowing an easy share, publish and deploy of the developed models., This work was supported by the project DEEP-Hybrid-DataCloud ‘‘Designing and Enabling E-infrastructures for intensive Processing in a Hybrid DataCloud’’ that has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant 777435.

Pelvic fracture urethral injury (PFUI) is relatively rare injury, and delayed urethroplasty is the gold standard for its repair. Because a failed urethroplasty results in increased scarring and reduced length of the available urethral segment, the salvage urethroplasty is a urologic challenge. We herein report the case of male patient with PFUI who could be salvaged after three failed urethroplasties. A 22-year-old male who had received a PFUI when he was 4 years old was referred for salvage urethroplasty after two perineal anastomotic urethroplasties and one transpubic urethroplasty had failed, leaving him unable to void and forced to keep having a suprapubic tube placed. The meatus was iatrogenically obliterated due to repeated treatments. Through an incision from the scrotum and right side of the root of the penis to the lower abdomen, the anterior urethra was circumferentially mobilized and transected at the distal urethral stump. The proximal urethral end was identified by palpitation with a metallic sound inserted through the suprapubic tube tract. The covering fibrotic scar tissue was completely removed and 8 anastomotic 4-0 polydioxanone sutures were placed to reapproximate the urethral mucosa. A pedicled gracilis muscle flap was created and wrapped around the anastomosis site and intrapelvic segment of the mobilized anterior urethra. A urethrogram 8 months after urethroplasty showed a wide caliber at the anastomosis site and a ventral midline meatotomy was subsequently performed. He is currently free from any instruments and can void well without the need for further intervention.

We report a case of bilateral synchronous testicular tumors, which was difficult to differentiate from malignant lymphoma. A 56-year-old man with a left scrotal mass was referred to our hospital. Ultrasonography revealed a uniformly hypoechoic mass in bilateral testes. Magnetic resonance imaging also revealed a homogeneously low-intensity lesion in the bilateral testes on T2-weighted images. Abdominal and chest computed tomography showed no lymphadenopathy or metastasis. The image findings at that time suggested a malignant lymphoma, and consequently, we performed a right radical orchiectomy. Histopathological examination revealed typical seminoma in the right testis; following this observation, left radical orchiectomy was performed, and the patient was diagnosed with synchronous bilateral testicular germ cell tumors. No recurrence or metastasis has been detected postoperatively. We recommend that the diagnosis of bilateral testicular tumors be made on the basis of patients' age, tumor marker level, and image findings.

Objective To examine whether the type of delayed urethroplasty required for pelvic fracture urethral injury, which is not easily predicted from conventional urethrography findings, can be predicted from preoperative magnetic resonance imaging (MRI) results. Patients and Methods Records of 74 male patients with pelvic fracture urethral injury who underwent MRI of the pelvis at least 3 months after injury and, subsequently, delayed anastomotic urethroplasty were retrospectively analyzed. Pubourethral stump length (PUL) was defined as the distance between the distal end of the proximal urethral stump and the lower border of the inferior pubic ramus. Pubourethral stump angle (PUA) was defined as the angle between the long axis of the pubis and the line between the distal end of the proximal urethral stump and the lower border of the inferior pubic ramus. Both PUL and PUA were measured in sagittal T2-weighted MRI. Results Delayed urethroplasty was performed by a simple perineal approach in the 28 patients requiring only bulbar urethral mobilization with or without corporal splitting and by elaborate approach in the 46 additionally requiring inferior pubectomy or an abdominoperineal approach with urethral rerouting. The overall success rate defined as no recurrent stricture on urethroscopy was 94.6%. Disruption at the prostate apex, greater urethral gap length, longer PUL, and lower PUA were in univariate analysis significantly associated with an elaborate approach. In multivariate analysis, only low PUA was an independent predictor of the need for an elaborate approach. Conclusion PUA measured on MRI is useful for predicting the type of reconstruction needed for urethral repair.

Purpose: We examined the impact on urethral stricture complexity at urethroplasty of previous transurethral treatments such as dilation, urethrotomy and stenting, which are most commonly performed when treating male urethral stricture.Materials and Methods: We retrospectively reviewed the records of 45 males who had undergone transurethral treatments before urethroplasty. We compared urethrography findings at initial diagnosis with those at urethroplasty. Males with failed hypospadias repair, lichen sclerosis or a history of prior urethroplasty were excluded from analysis. We considered stricture complexity increased if the number and/or length of strictures on urethrography at urethroplasty was greater than that at initial diagnosis or false passage was newly identified.Results: Of the patients 39 (87%), 32 (71%) and 13 (29%) had undergone urethral dilation, urethrotomy and urethral stenting, respectively, and 39 (87%) had undergone repeat or multiple kinds of transurethral treatments. Stricture complexi...

Atrial fibrillation (AF), especially asymptomatic cases, is often detected by medical checkups. We investigated the outcome of AF ablation in cases detected by medical checkups. We reviewed the data of 735 patients with AF (56 ± 10 years, paroxysmal: 441 patients) who underwent initial catheter ablation. All patients were divided into two groups based on their AF being diagnosed either by a medical checkup (group M) or not (group NM). AF was diagnosed by medical checkups in 263 (36%) patients. In Group M, the age was younger, time from the diagnosis to ablation shorter, left atrium dimension larger, and left ventricular ejection fraction lower than in Group NM. Male gender, persistent AF, and asymptomatic AF were more frequently seen in Group M than in Group NM. A mean of 13 ± 11 months after the initial ablation procedure, AF recurrence was more frequently observed in group M compared to group NM (P = 0.018). While the AF recurrence rate was similar in both groups in persistent AF patients (P = 0.87), it was more frequently observed in Group M than in Group NM in paroxysmal AF patients (P = 0.005). AF diagnosed by medical checkups was often associated with a worse outcome of catheter ablation, especially in paroxysmal AF patients.

Partial nephrectomy is the treatment of choice for small renal cell carcinoma (RCC) from the perspective of cancer management and renal function. However, when patients with RCC are of advanced age, exhibit severe comorbidities, including cardiovascular and pulmonary diseases, or have hereditary RCC, ablative therapies, including radiofrequency ablation (RFA) and cryoablation are useful treatment options. In the present study, the clinical outcomes of percutaneous RFA for treating small RCC were evaluated. Between December 2005 and March 2015, 40 patients (41 renal tumors in total) underwent RFA and a total of 50 sessions of RFA were performed. The average tumor size was 2.5 cm. A total of 18 tumors were exophytic and 23 were parenchymal. Of the 41 tumors, 85.4% were completely ablated by initial RFA and the rate of complete ablation following reablation for residual viable lesions was 95.1%. Local recurrence-free survival following complete ablation was 84.2% at 3 years. A patient with a 4.7 cm RCC tumor rapidly progressed following four RFA treatments until complete ablation was achieved. The metastasis-free survival rate following initial RFA was 95.7% at 3 years. The RCC-specific survival was 100% (mean follow-up, 38 months). Adverse events occurred in five sessions (10%); however, only 1 patient with arteriovenous fistula required intervention (transarterial embolization). The mean hospital stay following RFA was 3.2 days. The mean decrease in estimated glomerular filtration rate following RFA was 2.7%. The results of the present study indicate that percutaneous RFA was an effective treatment for small RCCs with respect to management of cancer, minimal invasiveness and minimal loss of renal function, particularly in patients for whom surgery would be a high risk and those at increased risk of deterioration of renal function.

Relative dose intensity (RDI) is a simple index for evaluation of the amount of drug administered per unit time. We retrospectively investigated the prognostic impact of RDI for patients with metastatic renal cell carcinoma (mRCC) treated with second-line targeted therapy.We enrolled 168 patients with mRCC. We assessed RDI at 4 weeks after second-line targeted therapy induction.The median follow-up after second-line targeted therapy was 18.1 months. The median time-to-treatment-failure (TTF) and overall survival (OS) were 4.9 and 25.4 months, respectively. In the Kaplan-Meier analysis, the median OS of patients with second-line RDI 0.7 was significantly shorter than those with RDI ≥ 0.7 (12.1 vs. 31.3 months; P = .030). In the subgroup analysis, second-line RDI was definitely prognostic in the poor-risk group of the International Metastatic Renal Cell Carcinoma Database Consortium criteria, showing second-line RDI was an independent predictor for both TTF (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.0; P = .002) and OS (HR, 3.1; 95% CI, 1.1-8.4; P = .026). Also, assessing the type of second-line regimen, the multivariate analysis showed that second-line RDI was an independent prognostic indicator of TTF (HR, 1.7; 95% CI, 1.0-2.9; P = .040) and OS (HR, 2.7; 95% CI, 1.3-5.7; P = .009) in patients treated with everolimus. In this group, the median TTF and OS of patients with RDI 0.7 were 2.4 and 11.1 months, and those with RDI ≥ 0.7 were 5.3 and 25.9 months, respectively.The results suggest that second-line RDI may be a prognostic predictor for patients with mRCC treated with second-line targeted therapy, particularly in both the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and everolimus-treated group.

Pazopanib is an orally bioavailable tyrosine kinase inhibitor anticancer drug approved worldwide for the treatment of metastatic renal cell carcinoma and advanced soft tissue sarcoma. Here we report the case of a patient whose recurrent retroperitoneal soft tissue sarcoma showed a drastic reduction immediately after pazopanib administration accompanied by severe liver dysfunction. His liver function was restored conservatively by giving him hepatoprotectors and having him stop taking pazopanib. The recurrent tumor disappeared but by 4 months later had regrown. Keywords: Liver toxicity, Pazopanib, Recurrent soft tissue sarcoma

To compare the clinical courses of patients with straddle injuries to the bulbar urethra based on the initial management strategy for urinary drainage, mainly suprapubic tube placement (SPT) and primary realignment (PR), and to examine whether PR has a beneficial effect on subsequent urethroplasty with regards to surgical and patient-reported outcomes.We reviewed the clinical courses of 126 patients with bulbar urethral stricture following straddle injuries who underwent delayed urethroplasty between August 2010 and April 2019. Patients were categorized as being initially treated with SPT (82 patients) or PR (44 patients). Stricture was considered complicated if preoperative urethrography or cystoscopy revealed iatrogenic scarring or a stricture away from the injury site.The percentage of patients who experienced delayed transurethral treatment at least once before referral was significantly higher in patients treated with PR than in those treated with SPT (25/44, 56.8% vs 16/82, 19.8%, P.0001). Although there was no difference in stricture length in both cohorts, the fraction of patients with complicated stricture was significantly higher in patients treated with PR than in those treated with SPT (15/44, 34.1% vs 14/82, 17.1%, P = .003). There was no significant difference in the selected type of urethroplasty, operative time, blood loss, success rate, postoperative maximum urinary flow rate, voiding symptoms, or erectile function between the 2 groups.PR does not facilitate delayed urethroplasty and had no beneficial effect on urethroplasty outcome. PR might lead to delayed transurethral procedures, resulting in increased risk of complicated strictures.

Recent large clinical trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced cardiovascular events in diabetic patients. However, the regulation and functional role of cardiac SGLTs (SGLT1 is the dominant isoform) compared with those of other glucose transporters (insulin-dependent GLUT4 is the major isoform) remain incompletely understood. Given that glucose is a preferential substrate for myocardial metabolism during ischemia-reperfusion injury (IRI), we hypothesized that SGLT1 contributes to cardioprotection during IRI via enhanced glucose transport, particularly in insulin-resistant phenotypes. The hearts from mice fed a high-fat diet (HFD) for 12 weeks or a normal-fat diet (NFD) were perfused with either non-selective SGLT-inhibitor phlorizin (to inhibit SGLT1) or selective SGLT2-inhibitors (tofogliflozin, ipragliflozin, canagliflozin) during IRI using Langendorff model. After ischemia-reperfusion, HFD impaired left ventricular developed pressure (LVDP) recovery compared with NFD. Although phlorizin-perfusion impaired LVDP recovery in NFD, a further impaired LVDP recovery and dramatically increased infarct size (indicated by CPK release into perfusate and TTC staining) were observed in HFD with phlorizin-perfusion. Meanwhile, none of the SGLT2-inhibitors significantly affected cardiac function or myocardial injury after ischemia-reperfusion under either diet condition. The plasma membrane expression of GLUT4 was significantly increased after IRI in NFD but was substantially attenuated in HFD, the latter of which was associated with a significant reduction in both myocardial glucose uptake and cardiac tissue ATP content. In contrast, regardless of the diet condition, SGLT1 expression remained constant during IRI, whereas SGLT2 was not detected. Of note, phlorizin considerably reduced myocardial glucose uptake and decreased cardiac tissue ATP content after IRI, particularly in HFD. In conclusion, cardiac SGLT1 but not SGLT2 plays a compensatory protective role and contributes to cardiac energy metabolism during acute phase of IRI via enhanced glucose utilization, particularly under insulin-resistant conditions, in which IRI-induced GLUT4 upregulation is compromised.

Background As a member of the Rho small guanosine triphosphatase family, ras-related C3 botulinum toxin substrate 1 (RAC1) interacts with various specific effectors, and p21-activated kinase 1 (PAK1), which has a role in both carcinogenesis and cellular invasion, binds to RAC1, after which activated PAK1 regulates cellular functions. There have been few reports about the simultaneous analysis of RAC1 and its downstream effector PAK1 in upper urinary tract urothelial carcinoma (UTUC). We assessed the expressions of both RAC1 and PAK1 and evaluated their association with clinicopathological parameters. Methods Immunohistochemical studies of RAC1 or PAK1 were performed with specimens from 104 patients with N0M0 UTUC and cancer-free surgical margins. Correlation of the positive expression of RAC1 or PAK1 or both with clinicopathological parameters was evaluated. Results A hazard model showed that the presence of mixed histologic features and moderate or strong positive expression of both RAC1 and PAK1 were independent factors for shortened disease-specific survival time (Ps = 0.041 and 0.016, respectively), and another hazard model revealed that only moderate or strong positive expression of both RAC1 and PAK1 was an independent factor for shortened recurrence-free survival time in the multivariate analysis (P = 0.036). Neither moderate or strong positive expression of RAC1 alone nor moderate or strong positive expression of PAK1 alone was an independent factor for a worse rate of disease-specific or recurrence-free survival in multivariate analysis. Conclusions Patients with N0M0 UTUC, cancer-free surgical margins and moderate or strong positive expression of both RAC1 and PAK1 should be carefully monitored after surgery.

Purpose: Prostate cancer management includes identification of clinically significant cancers that may require curative treatment. Statistical models based on gamma distribution can describe diffusion signal decay curves of prostate cancer. The purpose of this study was to evaluate the ability of parameters obtained with the gamma model in differentiating prostate cancers with different Gleason score values. Methods: This study included 155 patients with prostate cancer who underwent multiparametric magnetic resonance imaging prior to prostate biopsy (127 patients) or radical prostatectomy (28 patients) between January 2015 and June 2017; 159 foci of prostate cancer were included in our study. We compared cases scored as Gleason score (GS) 3 + 3 and GS ≥ 3 + 4, and analyzed cases scored as GS ≤ 3+ 4 and GS ≥ 4 + 3 based on the gamma model (Frac < 1.0, Frac < 0.8, Frac < 0.5, Frac < 0.3, and Frac > 3.0), and apparent diffusion coefficient (ADC). Results: Among 159 cancerous lesions in 155 patients, 13 (8.2%) were GS 3 + 3 prostate cancers, 51 (32.0%) were GS 3 + 4 prostate cancers, 30 (18.2%) were GS 4 + 3 cancers, and 65 (40.9%) were GS ≥ 4 + 4 cancers. Frac < 0.3, Frac < 0.5, Frac < 0.8, and Frac < 1.0 were significantly higher and ADC values were significantly lower in GS ≥ 4 + 3 cancers than in GS ≤ 3 + 4 cancers (P < 0.01, P < 0.01, P < 0.01, P = 0.01, and P < 0.01, respectively). With receiver operating characteristic (ROC) analysis, Frac < 0.3 and Frac < 0.5 had significantly greater area under the ROC curve for discriminating GS ≥ 4 + 3 cancers from GS ≤ 3 + 4 cancers than ADC (P = 0.03, P < 0.01, respectively). Conclusion: Frac < 0.3 and Frac < 0.5 showed higher diagnostic performance than ADC for differentiating GS ≥ 4 + 3 from GS ≤ 3 + 4 cancers. The gamma model may add additional value in discrimination of tumor grades.

Chronic kidney disease (CKD) is a common condition among elderly patients and has been reported to be a biomarker for the presence of malignant disease. In addition, unfavorable outcomes for patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy can be due to independent clinical factors. Therefore, the present study analyzed the clinicopathological data of patients with UTUC, who underwent radical nephroureterectomy at our institution, to clarify whether preoperative CKD and other factors are independent predictors of the shorter disease-specific and/or recurrence-free survival time of these patients. A retrospective review of 187 patients who underwent radical nephroureterectomy was conducted, and patients were followed for at least 3 months postoperatively. The clinicopathological factors that are thought to have potentially significant roles in the progression and metastasis of malignant tumors and for disease-specific and recurrence-free survival were evaluated. Positive surgical margins and an estimation of the glomerular filtration rate (eGFR) of

The current study aimed to investigate the plausible histopathological factors that affect the detectability of prostate cancers on multiparametric magnetic resonance imaging (MP-MRI). This retrospective study included 59 consecutive patients who had undergone MP-MRI and subsequent radical prostatectomy. The cases were standardized according to the tumor size ranging from 10 to 20 mm on the final pathological diagnosis. Histopathological review and semi-automated imaging analysis were performed to evaluate the relative area fractions of the histological components, including cancer cells, stroma, and luminal spaces. Among the 59 prostatectomy specimens, no case showed two or more foci of cancer that matched the size criteria. Of the 59 lesions, 35 were MRI-detectable [Prostate Imaging Reporting and Data System (PIRADS) score of 3 or greater] and 24 were MRI-undetectable (PIRADS score of 2 or less). No significant differences were observed in Gleason Grade Group, percentage of Gleason pattern 4, and predominant subtype of Gleason pattern 4 between MRI-detectable and MRI-undetectable cancers. On the other hand, significantly higher mean area fraction of cancer cells (60.9% vs. 42.7%, P

PURPOSE We aimed to evaluate whether increased nucleophosmin expression predicts recurrence and survival in upper tract urothelial carcinoma (UTUC). METHODS Specimens from 101 patients with N0M0 UTUC undergoing radical nephroureterectomy were evaluated. Nucleophosmin expression was determined immunohistochemically and categorized into two groups according to nucleophosmin staining intensity. The association between nucleophosmin expression and various clinicopathological factors including Ki-67 expression was analyzed. Multivariate analyses were performed to identify the independent predictors of extraurothelial recurrence and cancer-specific survival. RESULTS High nucleophosmin expression was significantly correlated with tumor location, pT ≥3, lymphovascular invasion, lymph node metastasis, and high Ki-67 expression. Patients whose tumors demonstrated high nucleophosmin expression had a significantly higher rate of extraurothelial recurrence and a lower survival rate than those with low nucleophosmin expression. Multivariate analysis showed that pT ≥3, lymph node metastasis, high nucleophosmin expression, and high Ki-67 expression were independent predictors of extraurothelial recurrence. When patients were stratified into three groups according to the number of risk factors, the 2-year extraurothelial recurrence-free survival rates were 92.9% in patients with 0 or 1 risk factor, 76.5% in patients with 2 risk factors, and 9.1% in patients with 3 or 4 risk factors. Regarding cancer-specific survival, lymphovascular invasion and high nucleophosmin expression were independent predictors. CONCLUSIONS Increased nucleophosmin expression was a strong predictor of extraurothelial recurrence and cancer-specific survival in patients with N0M0 UTUC undergoing radical nephroureterectomy. Our risk stratification models integrating nucleophosmin expression may provide valuable information on disease recurrence and prognosis.

Two risk models, the Memorial Sloan Kettering Cancer Center (MSKCC) model and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, have been studied in metastatic renal cell carcinoma (mRCC) treated with targeted therapy.To validate externally the predictive accuracies of the MSKCC and IMDC models for prognosis in mRCC patients treated with first-line and subsequent second-line targeted therapy.A total of 311 patients were assessed retrospectively.All patients underwent targeted therapy.Survival outcomes were assessed using Kaplan-Meier analysis. The predictive ability was evaluated using the c-index.Regarding to the first-line targeted therapy, the 3-yr overall survival (OS) rates of the MSKCC (p0.001) and IMDC models (p0.001) were 76.2% and 77.3%, respectively, in the favorable-risk group; 46.7% and 47.9%, respectively, in the intermediate-risk group; and 13.4% and 15.6%, respectively, in the poor-risk group. The c-indexes were 0.68 for the MSKCC model and 0.69 for the IMDC model in a first-line setting. Regarding the second-line targeted therapy, the 1-yr OS rates of the MSKCC (p0.001) and IMDC models (p0.001) were 80.9% and 90.5%, respectively, in the favorable-risk group; 71.4% and 70.6%, respectively, in the intermediate-risk group; and 31.7% and 24.6%, respectively, in the poor-risk group. The c-indexes were 0.66 for the MSKCC model and 0.65 for the IMDC model in the second-line setting. The study is limited by its retrospective nature.The results may assist physicians in providing more appropriate patient counseling and imply the need for a future prognostic tool in mRCC treated with targeted therapy.Both risk models were useful for the risk stratification in metastatic renal cell carcinoma (mRCC) patients treated with first-line and second-line targeted therapy; however, it might be necessary to further update or optimize the models for our Japanese cohort of mRCC patients.