Single-surgeon experience of excision and primary anastomosis for bulbar urethral stricture: analysis of surgical and patient-reported outcomes.

PURPOSE: To report our experience with excision and primary anastomosis (EPA) for bulbar urethral stricture. METHODS: 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. RESULTS: 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 < 0.0001 for all comparisons). However, five-point or greater deterioration in the SHIM score was found in 41 patients (19.1%). Regarding patient satisfaction, 98.6% of patients (212/215) were "satisfied" (32.6%) or "very satisfied" (66.0%) with the outcome. A low postoperative LUTS-total score and Peeling's picture score were independent predictors of a "very satisfied" patient (p = 0.001 and p = 0.01, respectively). CONCLUSIONS: EPA had a high success rate and was associated with significant benefits in both subjective and objective outcomes. Contrarily, a high incidence of postoperative erectile dysfunction was observed.

Is pre-referral management of anterior urethral strictures prior to urethroplasty appropriate?

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 < 0.0001), voiding with intermittent dilation (odds ratio 2.38, 95% confidence interval 1.38-4.12; P = 0.002), iatrogenic stricture (odds ratio 11.18, 95% confidence interval 5.30-23.61; P < 0.0001), and stricture longer than 20 mm (odds ratio 3.05, 95% confidence interval 1.47-6.38; P = 0.003) were the independent predictors of inappropriate use of transurethral procedures. CONCLUSIONS: Transurethral procedures are often inappropriately used. There is a clear need to promote appropriate management strategies for urethral strictures among general urologists.

Triangular extension of hinge flaps: A novel technique to resolve stomal stenosis and prevent restenosis in staged buccal mucosal urethroplasty.

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.

Surgical and patient-reported outcomes of urethroplasty for bulbar stricture due to a straddle injury.

PURPOSE: To report our experience with urethroplasty for bulbar stricture due to a straddle injury based on surgical and patient-reported outcomes. METHODS: 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. RESULTS: 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 < 0.0001, p = 0.004, p < 0.0001, respectively). All patients were either "satisfied" (19/84, 22.6%) or "very satisfied" (65/84, 77.3%). Lower postoperative LUT symptom score was an independent predictor of a "very satisfied" patient (odds ratio 0.81, 95% confidence interval 0.67-0.98, p = 0.002). CONCLUSIONS: Urethroplasty for bulbar stricture due to a straddle injury has a high success rate and is beneficial for both subjective and objective symptoms.

Difficulty in differential diagnosis for renal cancer with microscopic papillary architecture: overlapped pathological features among papillary renal cell carcinoma (RCC), mutinous tubular and spindle cell carcinoma, and unclassified RCC. Lessons from a Japanese multicenter study.

OBJECTIVES: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC. METHODS: We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features. RESULTS: All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3 years. CONCLUSION: Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs.

Usefulness of a high-speed surgical air drill in pubectomy during delayed anastomotic urethroplasty for pelvic fracture urethral injury.

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 < 0.0001). CONCLUSIONS: Surgical air drills might facilitate pubectomy in patients undergoing delayed anastomotic urethroplasty for pelvic fracture urethral injury. This tool offers the advantage of a delicate bone resection with reduced blood loss.

Evaluation of the effect of urethroplasty for anterior urethral strictures by a validated disease-specific patient-reported outcome measure.

PURPOSE: To better understand our urethroplasty outcome, we translated the English version of a urethral stricture surgery patient-reported outcome measure (USS-PROM) into Japanese and used it to evaluate the effect of urethroplasty for anterior urethral strictures. METHODS: The PROM quantifies lower urinary tract symptoms (LUTS) and health-related quality of life (EQ-5D), and it evaluates overall satisfaction by asking patients to choose "very satisfied", "satisfied", "unsatisfied", or "very unsatisfied". 93 Japanese-speaking male patients with anterior urethral stricture who underwent urethroplasty completed it before (baseline) and 6 months after urethroplasty. The psychometric criteria evaluated in the present study were the PROM's internal consistency, test-retest reliability, criterion validity, and responsiveness. RESULTS: Qmax was negatively correlated with the LUTS-total scores (r = - 0.61). Cronbach's alpha was 0.80 and the test-retest intraclass correlation coefficient for the LUTS-total score was 0.82. 83 patients (89.2%) achieved stricture-free, which was defined as no re-stricture on cystoscopy and no need for additional treatment. The mean total LUTS-score improved from 12.4 at baseline to 3.7 postoperatively (p < 0.0001). The mean EQ-5D visual analogue scores and EQ-5D index improved from 61.2 and 0.76, respectively, at baseline to 77.9 and 0.89 postoperatively (p < 0.0001, p < 0.0001). 55 patients (59.1%) were "very satisfied" with the outcome of their urethroplasty and 33 (35.5%) were "satisfied". CONCLUSIONS: The Japanese version of the USS-PROM has adequate psychometric properties. Urethroplasty improved not only objective data but also voiding symptoms and health-related QOL, and it resulted in a high rate of patient satisfaction.

Single-surgeon series of delayed anastomotic urethroplasty for pelvic fracture urethral injury: an analysis of surgical and patient-reported outcomes of a 10-year experience in a Japanese referral center.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.0001), EQ-5D index scores (p < 0.0001), and EQVAS scores (p < 0.0001) all improved significantly after urethroplasty. CONCLUSIONS: Delayed anastomotic urethroplasty has a high success rate and significant beneficial effects on both LUTS-specific and health-related QOL, resulting in high patient satisfaction. Careful manipulation in a bloodless operative field by experienced surgeons could be the key to successful urethroplasty.

Sub-classification of patients with intermediate-risk metastatic renal cell carcinoma treated with targeted therapy.

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.

Impact of inflammatory marker levels one month after the first-line targeted therapy initiation on progression-free survival prediction in patients with metastatic clear cell renal cell carcinoma.

OBJECTIVES: 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. METHODS: Two hundred and fifteen patients whose tumors were clear cell type and in whom first-line targeted therapies could be continued for >1 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. RESULTS: The 1-year progression-free survival rate was 47%. Female gender, Karnofsky performance status <80%, time from diagnosis to systemic treatment <12 months, pretreatment C-reactive protein >3.0 mg/dl and post-treatment neutrophil-to-lymphocyte ratio >3.0 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 (P < 0.0001). Furthermore, there were also significant differences in overall survival rates between the groups (P < 0.0001). CONCLUSIONS: 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.

Insulin-like growth factor 1 sustained-release collagen on urethral catheter prevents stricture after urethral injury in a rabbit model.

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 < 0.0001). In addition, five of the seven rabbits in group 1 (71.4%) had a urethral lumen large enough for passage of a urethroscope, a fraction larger than the corresponding fractions in groups 2 (57.1%) and 3 (20%). On histological analysis, the injured area not covered with regenerated urethral epithelium tended to be smaller in group 1 than the other two groups, but the mean difference was not significant (P = 0.19). CONCLUSIONS: An insulin-like growth factor 1 sustained-release collagen urethral catheter significantly improves wound healing and prevents urethral stricture after urethral injury.

Do Transurethral Treatments Increase the Complexity of Urethral Strictures?

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 complexity was increased in 22 men (49%) while 7 (16%) required urethroplasty more complex than that anticipated from urethrography findings at initial diagnosis. Increased stricture complexity was significantly associated with a history of urethrotomy (p = 0.03), urethral stenting (p = 0.0002) and repeat transurethral treatments (p = 0.01). Multivariate analysis revealed that urethral stenting (p = 0.01) and repeat transurethral treatments (p = 0.01) were independent predictors of increased stricture complexity. CONCLUSIONS: Repeat transurethral treatments increase stricture complexity and are potentially counterproductive. Even a single application of temporary urethral stenting carries a high risk of complicating the stricture and requiring complex urethroplasty.

Ritonavir and ixazomib kill bladder cancer cells by causing ubiquitinated protein accumulation.

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.

Increased nucleophosmin expression is a strong predictor of recurrence and prognosis in patients with N0M0 upper tract urothelial carcinoma undergoing radical nephroureterectomy.

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.

Role of lymph node dissection during radical nephroureterectomy for upper urinary tract urothelial cancer: multi-institutional large retrospective study JCOG1110A.

PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

[A CASE OF METASTATIC BLADDER UROTHELIAL CARCINOMA WHOSE DISEASE WAS CONTROLLED FOR A RELATIVE LONG PERIOD BY MULTIDISCIPLINARY TREATMENT INCLUDING RADIATION TO A LUNG METASTASIS AND MULTIPLE COURSES OF CHEMOTHERAPY].

A 67-year-old woman complained of urinary frequency and gross hematuria. She was referred to our hospital with the diagnosis of bladder tumor. Transurethral resection of the bladder tumor (TURBT) was performed and pathological diagnosis was urothelial carcinoma (G2>G3) with muscular invasion. Because she hoped bladder preservation therapy, she received two courses of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) therapy, one course of arterial infusion chemotherapy, and chemoradiotherapy with cisplatin. After those therapies she underwent 4 times of TURBT and two courses intravesical BCG therapy. However, solitary lung metastasis appeared 19 months after the initial TURBT. Multidisciplinary treatments including 25 courses of various multiagent chemotherapies, radiation therapy to the lung metastasis and surgical resection of a urethral recurrence were performed. Although a localized radiation pneumonitis was developed, the lung metastasis appeared to be controlled for 26 months after the radiation therapy to the lung. Bilateral ureteral and renal pelvic tumors appeared after the radiation therapy. Severe bleeding was occurred from renal pelvic tumors several times and she needed the hospital stay 2 times. Active bleeding stopped after the administration of chemotherapy each time. Although she died of occlusive jaundice due to the liver metastasis, she had been alive due to the multidisciplinary treatment for 67 months after lung metastasis appearance with relatively good performance status.

[CLINICAL ANALYSIS ABOUT PERCUTANEOUS NEEDLE BIOPSY FOR RENAL MASSES].

(Objective) We investigated the efficacy and safety of percutaneous renal mass biopsy retrospectively. (Methods) A retrospective review was performed of 44 patients (46 renal masses) who received ultrasound and/or computed tomography guided percutaneous biopsy of a solid renal mass between April 2004 and December 2012 in National Defense Medical College Hospital. (Results) The median renal mass size was 45 (range 15-140) mm with a median of 2 (1-5) cores taken. Thirteen masses were biopsied for differential diagnosis between RCC and other malignancies (or benign renal tumors), 11 were biopsied for differential diagnosis between RCC and renal pelvic urothelial carcinoma, 10 unresectable masses were biopsied to confirm the diagnosis pathologically before starting medication, and 12 small masses were biopsied before radio-frequency ablation. Of the initial 46 biopsies, 38 (82.6%) were diagnostic. The median lesion sizes in the diagnostic and nondiagnostic biopsy specimens were 45 (15-140) mm and 43 (17-128) mm. The median numbers of diagnostic and nondiagnostic cores were 2 (1-5) and 1.5 (1-4). These size and core number differences between the diagnostic and nondiagnostic biopsy specimens are not statistically significant. Of initial nondiagnostic 8 masses, 3 masses that were performed repeat biopsy resulted in determined diagnosis finally. There were mild postprocedural hematomas not requiring blood transfusion. There was no tumor dissemination after renal mass biopsy. (Conclusions) Percutaneous biopsy of renal masses is a safe procedure that provides diagnostic information.

A pilot study of photoacoustic imaging system for improved real-time visualization of neurovascular bundle during radical prostatectomy.

BACKGROUND: Photoacoustic imaging, a noninvasive imaging based on optical excitation and ultrasonic detection, enables one to visualize the distribution of hemoglobin and acquire a map of microvessels without using contrast agents. We examined whether it helps visualize periprostatic microvessels and improves visualization of the neurovascular bundle. METHODS: We developed a photoacoustic imaging (PAI) system with a hand-held probe combining optical illumination and a conventional linear array ultrasound probe. In experiments with a phantom model, it was able to visualize vessels with diameters as small as 300 µm within a depth of 10 mm. We also developed a TRUS type probe for our photoacoustic imaging system and used it to intraoperatively monitor periprostatic tissues in seven patients with clinically organ-confined prostate cancer who were undergoing non-nerve-sparing retropubic radical prostatectomy. Images of periprostatic tissues from resected prostatectomy specimens were also obtained using the linear photoacoustic probe, and the consistency of the microvessel distribution and co-existence of nerve fibers was examined by double immunostaining of paraffin-embedded sections with anti-CD31 and anti-S-100 antibodies. RESULTS: Intraoperative monitoring of periprostatic tissues with the TRUS photoacoustic probe showed substantial signals on the posterolateral surface of the prostate and clearly demonstrated the location and extent of the neurovascular bundle better than does TRUS alone. Photoacoustic images of the periprostatic tissues in resected specimens also showed substantial signals that were especially strong on the posterolateral surface of the prostate. Nerve fibers were closely co-localized with periprostatic microvessels and the pattern of their distribution was consistent with that of PAI signals. CONCLUSIONS: The intraoperative photoacoustic imaging located the microvascular complex in the neurovascular bundle. Moreover, the neurovascular bundle was easier to identify by PAI than by TRUS alone, suggesting that PAI could be helpful in nerve-sparing radical prostatectomy.

[Metastatic Renal Cell Carcinoma in Paranasal Sinus for which Periodic Drug Withdrawal Schedule of Axitinib was Effective : A Case Report].

A 73-year-old male patient underwent a right nephrectomy for renal cell carcinoma in 2008, and interferon-alpha was initiated as adjuvant treatment. Computed tomography (CT) scans showed lymphadenopathy above the left diaphragm, and treatment with interferon-2 was subsequently initiated in 2009. Nasal bleeding manifested in February 2010, and CT scans showed a soft-tissue density mass mainly located in the ethmoid sinus. A biopsy of the lesion was performed, and metastatic renal cell carcinoma was diagnosed. Treatment with sorafenib was consequently initiated and the paranasal metastasis showed a temporary partial response (PR). However, the metastatic lesion increased in size and caused repeated nasal bleeding that required blood transfusion. Although treatment with everolims was initiated, adverse events, such as rush, hypertensionnemia, and anemia due to nasal bleeding, developed. Treatment with axitinib was subsequently initiated. However, because adverse events, such as severe diarrhea, renal dysfunction and proteinuria manifested, the dose of axitinib was gradually decreased, and a periodic drug withdrawal schedule (11 days on, 3 days off) was finally initiated, which controlled these adverse events. The metastatic lesions showed a PR for 31months following axitinib administration.

Anterior Prostate Cancer: Diagnostic Performance of T2-Weighted MRI and an Apparent Diffusion Coefficient Map.

OBJECTIVE: Diagnosis of anterior prostate cancer is challenging. The purpose of this study was to evaluate the diagnostic performance of T2-weighted imaging and an apparent diffusion coefficient (ADC) map in the detection of anterior prostate cancer and to compare that with the diagnostic performance in the detection of posterior prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the records of 87 patients who underwent 3-T MRI that included T2-weighted imaging and diffusion-weighted imaging before radical prostatectomy. The prostate gland was divided into anterior and posterior segments, and the radiologists interpreted two protocols (T2-weighted imaging alone vs T2-weighted imaging and an ADC map) and sorted the confidence levels for the presence of prostate cancer into five grades. ROC analysis was performed to evaluate the diagnostic performance of each protocol for the detection of anterior and posterior prostate cancers. We also assessed the relative fractions of sensitivity and specificity between anterior and posterior prostate cancers. Additionally, the ADCs of noncancerous anterior fibromuscular stroma were measured and compared with the ADCs of anterior prostate cancers. RESULTS: The AUCs with T2-weighted imaging alone and with T2-weighted imaging and an ADC map were 0.75 and 0.88 for anterior prostate cancer, respectively, and were 0.70 and 0.81 for posterior prostate cancer. The sensitivity for detecting anterior prostate cancer was 90% and was significantly higher than that for detecting posterior prostate cancer in the protocol using T2-weighted imaging and an ADC map (p = 0.003) when scores of 3-5 were considered as positive for prostate cancer. The ADC was significantly lower in anterior prostate cancer (mean, 0.80 × 10(-3) mm(2)/s) than in noncancerous anterior fibromuscular stroma (1.13 × 10(-3) mm(2)/s) (p < 0.001). CONCLUSION: The protocol using T2-weighted imaging and an ADC map showed higher accuracy for the detection of anterior prostate cancer than for the detection of posterior prostate cancer.