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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.

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.

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

Introduction We report a case of distal urethral carcinoma treated with segmental urethral excision and reconstruction by staged buccal mucosa urethroplasty. Case presentation A 60-year-old man presented with difficulty urinating and a palpable mass on the ventral side of his penis. He was diagnosed as having localized distal urethral carcinoma (cT2N0M0) and underwent penile-preserving surgery with staged urethroplasty using buccal mucosa as substitute tissue. The pathological diagnosis was squamous cell carcinoma of the urethra (T2) with negative surgical margin. At 2 years of follow-up, there was no recurrence or metastasis, he could void in a standing position with an acceptable urinary stream, and he found the appearance of his external genitalia acceptable. Conclusion In cases of distal primary urethral carcinoma, urethroplasty using buccal mucosa graft could be alternative treatment option providing a better postoperative quality of life.

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.

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

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.

Background/aim In the present study, the antineoplastic activity and mechanism of action of phenoxodiol, a novel isoflavone analog, was investigated in renal cancer cells. Materials and methods A panel of renal cancer cells (769-P, 786-O, Caki-2) was treated with phenoxodiol in vitro, and the efficacy of treatment was evaluated. Results MTS assay results showed that phenoxodiol decreased renal cancer viability in a dose-dependent manner. In addition, it inhibited colony formation significantly and perturbed the cell cycle. Treatment with phenoxodiol increased the number of annexin-V-positive cells as well as the expression of cleaved poly ADP ribose polymerase, demonstrating that phenoxodiol induced apoptosis in renal cancer cells. Phenoxodiol also inhibited Akt pathway via dephosphorylation of Akt. Conclusion Phenoxodiol inhibited Akt pathway and induced apoptosis of renal cancer cells. The present study provides a theoretical basis for future development of a novel therapy effective against renal cancer.

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...

Docosahexaenoic acid (DHA) has a variety of anti-tumor activities. The present study examined the anti-tumor activity of DHA in renal cancer cells and its underlying mechanisms of action. The effects of DHA on the viability and proliferation of the human renal cancer cell lines Caki-1 and 786-O were examined by an MTS assay and cell counting. In addition, cell cycle distribution and cell apoptosis were analyzed by flow cytometry and Annexin V staining, and modulation of cell mobility and invasiveness was assessed by wound healing and Matrigel invasion assays. Effects of DHA on intracellular signaling pathways were also analyzed by western blotting. It was observed that DHA significantly reduced the viability and proliferation of Caki-1 and 786-O cells (P

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.

To evaluate the impact of lymph node dissection (LND) on clinical outcome during radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC).We, the Urologic Oncology Study Group of the Japan Clinical Oncology Group (JCOG), retrospectively collected data from patients with non-metastatic UTUC who underwent RNU in 30 centers in 1995-2009. Ineligible patients and patients with previous and/or synchronous bladder cancer were excluded, and the remaining 2037 patients were analyzed. We compared overall and cancer-specific mortality between patients who underwent LND (LND group) and those without LND (no-LND group).Among 2037 patients, LND was performed in 1046 (51.4%) patients, and 223 (10.9%) patients had pathological node-positive (pN+) disease. All-cause mortality was observed in 503 patients (24.7%) during follow-up (median 45.8 months), including 363 patients (17.8%) who died of UTUC. Patients with pN+ disease showed significantly shorter overall survival (OS) compared with pN0 patients, and the estimated 5-year OS for pN+ patients was 30%. Older age, ≥cT3, and clinical node-positive disease were found as preoperative predictors for pN+ disease by multivariate analysis. In the comparison of OS and cancer-specific mortality between LND and no-LND groups, there was no significant improvement by LND in multivariate analysis. The median number of lymph nodes removed was six (IQR 3-11). There was no significant association between the number of lymph nodes removed and OS.The present study indicates that there is no therapeutic benefit of LND during RNU for UTUC, although pathologically positive LN status can predict poor prognosis.

There is no curative treatment for advanced bladder cancer. Causing ubiquitinated protein accumulation and endoplasmic reticulum stress is a novel approach to cancer treatment. The HIV protease inhibitor ritonavir has been reported to suppress heat shock protein 90 and increase the amount of unfolded proteins in the cell. If the proteasome functions normally, however, they are rapidly degraded. We postulated that the novel proteasome inhibitor ixazomib combined with ritonavir would kill bladder cancer cells effectively by inhibiting degradation of these unfolded proteins and thereby causing ubiquitinated proteins to accumulate. The combination of ritonavir and ixazomib induced drastic apoptosis and inhibited the growth of bladder cancer cells synergistically. The combination decreased the expression of cyclin D1 and cyclin-dependent kinase 4, and increased the sub-G1 fraction significantly. Mechanistically, the combination caused ubiquitinated protein accumulation and endoplasmic reticulum stress. The combination-induced apoptosis was markedly attenuated by the protein synthesis inhibitor cycloheximide, suggesting that the accumulation of ubiquitinated proteins played an important role in the combination's antineoplastic activity. Furthermore, the combination induced histone acetylation cooperatively and the decreased expression of histone deacetylases was thought to be one mechanism of this histone acetylation. The present study provides a theoretical basis for future development of novel ubiquitinated-protein-accumulation-based therapies effective against bladder cancer.

Renal cell carcinoma (RCC) is the most lethal urological malignancy with high risk of recurrence; thus, new prognostic biomarkers are needed. In this study, a new RCC antigen, PTPL1 associated RhoGAP1 (PARG1), was identified by using serological identification of recombinant cDNA expression cloning with sera from RCC patients. PARG1 protein was found to be differentially expressed in RCC cells among patients. High PARG1 expression is significantly correlated with various clinicopathological factors relating to cancer cell proliferation and invasion, including G3 percentage (P = .0046), Ki-67 score (p expression is also correlated with high recurrence of N0M0 patients (P = .0084) and poor prognosis in RCC patients (P = .0345). Multivariate analysis has revealed that high PARG1 expression is an independent factor for recurrence (P = .0149) of N0M0 RCC patients. In in vitro studies, depletion of PARG1by siRNA in human RCC cell lines inhibited their proliferation through inducing G1 cell cycle arrest via upregulation of p53 and subsequent p21Cip1/Waf1, which are mediated by increased RhoA-ROCK activities. Similarly, PARG1 depletion cells inhibited invasion ability via increasing RhoA-ROCK activities in the RCC cell lines. Conversely, overexpression of PARG1 on human embryonic kidney cell line HEK293T promotes its cell proliferation and invasion. These results indicate that PARG1 plays crucial roles in progression of human RCC in increasing cell proliferation and invasion ability via inhibition of the RhoA-ROCK axis, and PARG1 is a poor prognostic marker, particularly for high recurrence of N0M0 RCC patients.

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.

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.

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.

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.

The histone deacetylase (HDAC) inhibitor belinostat increases the amount of unfolded proteins in cells by promoting the acetylation of heat shock protein 90 (HSP90), thereby disrupting its chaperone function. The human immunodeficiency virus protease inhibitor ritonavir, on the other hand, not only increases unfolded proteins by suppressing HSP90 but also acts as a proteasome inhibitor. We thought that belinostat and ritonavir together would induce endoplasmic reticulum (ER) stress and kill renal cancer cells effectively. The combination of belinostat and ritonavir induced drastic apoptosis and inhibited the growth of renal cancer cells synergistically. Mechanistically, the combination caused ER stress (evidenced by the increased expression of the ER stress markers) and also enhanced histone acetylation by decreasing the expression of HDACs. To our knowledge, this is the first study that showed a beneficial combined effect of belinostat and ritonavir in renal cancer cells, providing a framework for testing the combination in renal cancer patients.

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.

There is no established treatment for advanced rhabdomyosarcoma (RMS) with metastases at the time of diagnosis. A 17-year-old male was referred to our hospital because of a right scrotal mass. Computed tomography showed multiple lung metastases with pleural effusion and retroperitoneal lymph node metastasis, and bone scintigraphy revealed multiple bone metastases. Right high orchiectomy was performed and the tumor was diagnosed as paratesticular embryonal RMS. He was treated with a multimodal therapy including 17 cycles of combination chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin and dacarbazine (CYVADIC) and achieved a long-term survival of 4 years.

The recent discovery and clinical development of targeted agents have expanded treatment options in metastatic renal cell carcinoma (RCC). However, metastatic RCC remains a lethal disease. Complete response is rare and treatment with targeted agents eventually fails in the majority of the patients. Therefore, there is a need for developing a prognostic tool and a novel therapeutic agent for RCC to improve the follow-up strategy after surgical treatment. Clinical data, including patient characteristics, serum fatty acid profile, clinicopathological parameters and clinical outcome, were obtained from 112 patients with RCC prior to surgical treatment. Preoperative fatty acid levels were grouped according to patient characteristics, such as performance status, body mass index or pathological parameters, and were analyzed using the Mann-Whitney U test. Cancer-specific survival in the high and low docosahexaenoic acid (DHA) level groups were compared using the Kaplan-Meier method. Cox proportional hazards models were applied to determine the independent prognostic factors associated with shortened cancer-specific survival. The serum DHA level in patients with metastasis was significantly lower compared with that in patients without metastasis (P=0.047). Low serum DHA level, presence of metastasis and cachexia were independent predictors of shortened cancer-specific survival in a multivariate Cox proportional hazard model (P=0.033, hazard ratio = 4.43). Patients with a serum DHA level below the median value exhibited significantly shorter cancer-specific survival compared with those with a higher serum DHA level (P=0.008). Thus, according to our results, the preoperative serum DHA level may be able to predict the surgical outcome of RCC. However, this finding requires validation by large-scale prospective studies.

The prediction of extraurothelial recurrence (EUR) before radical nephroureterectomy (RNU) is difficult for patients with upper tract urothelial carcinoma. If EUR can be predicted preoperatively, it may be possible to determine the need for neoadjuvant chemotherapy or the surgical strategy. Our previous study identified preoperative risk factors for EUR in ureteral cancer, while the present study identified preoperative risk factors for EUR in renal pelvic cancer (RPC). The preoperative factors were reviewed in 71 N0M0 patients with RPC treated by RNU between 1999 and 2013. Preoperative clinical background data, laboratory test results, including inflammatory indices, lactate dehydrogenase (LDH), and estimated glomerular filtration rate, and radiological findings were subjected to multivariate analyses to identify independent predictive factors for EUR. The 3-year EUR-free survival (EURFS) rate was 81.9%, and univariate analysis showed that clinical T (cT) stage ≥3, white blood cell counts ≥7600/µl, neutrophil counts ≥4,500/µl, neutrophil-to-lymphocyte ratio ≥2.0, and LDH ≥210 IU/l were significantly associated with EURFS. Additionally, a cT stage ≥3 (P=0.0244) and LDH ≥210 IU/l (P=0.0322) were independent predictors for EUR. When patients were stratified into three groups according to the number of risk factors, the 3-year EURFS rates were 94.5, 76.3, and 33.3% for the low-, intermediate-, and high-risk patient groups, respectively. In conclusion, cT stage ≥3 and LDH ≥210 IU/l were preoperative predictive factors of EUR in patients with RPC. High-risk patients may be candidates for neoadjuvant chemotherapy and low-risk patients may be candidates for RNU without lymph node dissection.

Primary lymphoma of the bladder is extremely rare. It represents less than 0.2% of all extranodal primary lymphomas and is usually extranodal marginal-zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT).1 We herein report a case of primary MALT lymphoma of the bladder in a 77-year-old female patient who was successfully treated with radiotherapy. This lymphoma was not diagnosed earlier because it coincided with chronic cystitis. Case presentation A 77-year-old female had suffered from pollakisuria, voiding pain, and gross hematuria and had presented to several hospitals. As a result, she had been diagnosed with chronic cystitis and treated for 2 years with antibiotics and anticholinergics. She was referred to our hospital because her symptoms had not improved. At the initial presentation, the patient still had pyuria and urine culture was positive for levofloxacin-resistant Escherichia coli. She was given cefcapene, but pyuria and gross hematuria persisted. Cystoscopy revealed reddish edematous mucosa on the posterior wall of the bladder (Fig. 1A) and pelvic MRI showed mass lesions on the anterior and posterior walls (Fig. 1B). Cytological examination was negative for urothelial cancer. Open in a separate window Fig. 1 Cystoscopy and MRI at presentation. Cystoscopy showed reddish edematous mucosa on the posterior wall of the bladder (A). MRI showed mass lesions on the anterior and posterior walls (B, arrows). T2-weighted image.

Intravesical bacillus Calmette–Guérin (BCG) instillation is broadly used to prevent bladder cancer recurrence or to treat carcinoma in situ. BCG infection is rare but can cause serious problems because this strain has intrinsic resistance to pyrazinamide, a first-line anti-tuberculosis drug. Furthermore, there had been no specific and easy procedure accurately diagnosing BCG infection. In this case report we present the first case of BCG cystitis diagnosed with a newly developed easy-to-use diagnostic procedure using the loop-mediated isothermal amplification method.

Small cell carcinoma (SCC) of the urinary bladder is highly aggressive and portends a poor outcome. Herein, we report a patient with recurrent SCC of the urinary bladder who experienced an unusually long-term disease-free duration after radical cystectomy. The patient was a 60-year-old woman who had undergone transurethral resection followed by radical cystectomy for muscle-invasive bladder cancer (high-grade urothelial carcinoma with adenocarcinomatous differentiation) 6 years prior; the surgical specimen had a negative surgical margin. She was referred to our hospital because of continuous bleeding from her vagina. Magnetic resonance imaging showed a mass located at the anterior wall of her residual vagina, a biopsy of which confirmed a pathological diagnosis of adenocarcinoma. The vaginal tumor and a section of the sigmoid colon were resected en bloc and were pathologically diagnosed as adenocarcinoma and SCC. We reevaluated the initial transurethral resection specimen and found SCC with foci of adenocarcinoma concomitant with high-grade urothelial carcinoma. Local recurrence and metastasis at the pelvic bone occurred 4 months later; although radiation therapy was performed, she died of the progressive disease.

OBJECTIVES To evaluate the preventive effect of an insulin-like growth factor 1 sustained-release collagen urethral catheter on urethral stricture after urethral injury in a rabbit model. METHODS We made urethral catheters coated either with insulin-like growth factor 1 impregnated collagen or with only collagen, and we divided 19 male Japanese white rabbits into three groups according to the kind of catheter inserted immediately after the rabbit's urethra was injured by electrocoagulation. Group 1 (n = 7) had a catheter coated with insulin-like growth factor 1 impregnated collagen inserted; group 2 (n = 7) had a catheter coated with only collagen inserted; and group 3 (n = 5) had an uncoated catheter inserted. A total of 14 days later, the injured urethras were evaluated by urethrography and urethroscopy, and were also histologically examined. RESULTS Urethrography showed that the ratio of the urethral lumen diameter in injured urethra to that in normal urethra was the largest in group 1 (P

Progression-free survival of first-line targeted therapy greatly influences the survival of patients with metastatic renal cell carcinoma. We evaluated whether post-treatment inflammatory markers and lactate dehydrogenase levels had impacts on progression-free survival prediction in addition to those of conventional predictors.Two hundred and fifteen patients whose tumors were clear cell type and in whom first-line targeted therapies could be continued for1 month were evaluated. Pretreatment clinical factors, pathological factors and laboratory data 1 month after targeted therapy initiation-including inflammatory markers (neutrophil count, neutrophil-to-lymphocyte ratio and C-reactive protein) and lactate dehydrogenase-were reviewed. To identify progression-free survival predictors, multivariate analyses were done.The 1-year progression-free survival rate was 47%. Female gender, Karnofsky performance status80%, time from diagnosis to systemic treatment12 months, pretreatment C-reactive protein3.0 mg/dl and post-treatment neutrophil-to-lymphocyte ratio3.0 were independent predictors for progression-free survival. In contrast, neither C-reactive protein increase nor neutrophil-to-lymphocyte ratio increase after targeted therapy initiation were independent predictors. Pretreatment lactate dehydrogenase, post-treatment lactate dehydrogenase and lactate dehydrogenase decline were not independent predictors. When all patients were stratified by these independent factors into three groups (0 risk vs. 1 or 2 risks vs. 3 or more risks), there were significant differences in progression-free survival rates between the groups (P0.0001). Furthermore, there were also significant differences in overall survival rates between the groups (P0.0001).Integration of post-treatment neutrophil-to-lymphocyte ratio value with pretreatment factors may lead to the establishment of effective predictive model for disease progression in patients with metastatic clear cell renal cell carcinoma who received first-line targeted therapies.