Fewer systematic prostate core biopsies in clinical stage T1c prostate cancer leads to biochemical recurrence after brachytherapy as monotherapy.

BACKGROUND: After brachytherapy, fewer prostate biopsy cores at diagnosis can underestimate the pathological characteristics of prostate cancer (PCa) with lower concordance, resulting in improper treatment, particularly in patients with low-risk nonpalpable cT1c PCa. The aim of this study was to assess the relationship between the number of biopsy cores at diagnosis and long-term clinical outcomes after brachytherapy for cT1c PCa. METHODS: We reviewed 516 patients with localized cT1c PCa with Gleason scores of 3 + 3 = 6 or 3 + 4 = 7 who underwent brachytherapy as monotherapy without hormonal therapy between January 2005 and September 2014 at our institution. Clinical staging was based on the American Joint Committee on Cancer manual for staging. Thus, the cT1c category is based solely on digital rectal examination. The primary outcome was biochemical recurrence (BCR). Based on the optimized cutoff value for biopsy core number obtained from receiver operating characteristic analysis, patients were divided into the biopsy cores ≤8 (N = 123) and ≥9 (N = 393) groups. The BCR-free survival rate was compared between the groups. Prognostic factors for BCR were evaluated, including age, initial prostate-specific antigen (PSA) level, Gleason score, positive core rate, PSA density, prostate magnetic resonance imaging findings, and biopsy core number. RESULTS: The median patient age was 66.0 years (interquartile range [IQR]: 61.0-71.0 years), and the median follow-up time was 11.1 years (IQR: 9.5-13.3 years). The median number of core biopsies was 12 (IQR: 9-12). The area under the curve was 0.637 (95% confidence interval [CI]: 0.53-0.75), and the optimal biopsy core cutoff value for BCR prediction was 8.5 (sensitivity = 43.5%, specificity = 77.1%). Although fewer patients had Gleason scores of 3 + 4 = 7 (19/123 [15%] vs. 125/393 [32%], p < 0.02) in the biopsy cores ≤8 group, the 10-year BCR-free survival rate was significantly lower in the biopsy cores ≤8 group than in the biopsy cores ≥9 group (93.8% vs. 96.3%, p < 0.05). Multivariate analysis revealed that a lower biopsy core number (hazard ratio: 0.828, 95% CI: 0.71-0.97, p < 0.03) and a Gleason score of 3 + 4 = 7 (hazard ratio: 3.26, 95% CI: 1.37-7.73, p < 0.01) significantly predicted BCR. CONCLUSIONS: A low number of prostate core biopsies results in worse BCR-free survival after brachytherapy as monotherapy in patients with cT1c PCa.

Secondary bladder cancer during long-term follow-up after iodine-125 permanent seed implantation for localized prostate cancer.

INTRODUCTION: Brachytherapy for prostate cancer treatment may induce secondary bladder cancer during long-term follow-ups. This study reviews the risk and tumor characteristics of secondary bladder cancer after brachytherapy. METHODS: This single-institution retrospective study included 1162 patients treated with low-dose-rate permanent seed implantation brachytherapy with iodine-125, with or without external beam radiation therapy, for localized prostate cancer. We calculated and compared the rates of secondary bladder cancer among patients treated with brachytherapy and radical prostatectomy (n = 218) before and after a propensity score-matching analysis. Possible risk factors for secondary bladder cancer, such as patient age and external beam radiation therapy administration, were analyzed. RESULTS: Of 1162 patients with a median follow-up period of 11.4 (range: 0.7-15.5) years, 26 presented with urothelial carcinomas and 1 with adenocarcinoma at a median of 8.9 (range: 2.9-14.0) years after brachytherapy, although the incidence rates of secondary bladder cancer after brachytherapy were not significantly different from those after radical prostatectomy. No significant risk factors for secondary bladder cancer were identified. The initial symptoms of secondary bladder cancer were gross hematuria (74%) and microscopic hematuria with positive urine cytology (15%). Among 26 cases of secondary urothelial carcinoma, 54% were high-grade and 46% were invasive. After brachytherapy, invasive urothelial carcinoma occurred later than noninvasive urothelial carcinoma (p = 0.01). CONCLUSIONS: Considering the aggressive malignancy of secondary bladder cancer, cystoscopy and urine cytology should be performed for further investigation of the causes of gross or microscopic hematuria and rule out secondary bladder cancer in cases followed longer than 3 years after brachytherapy.

Renal preservation by pure laparoscopic partial ureterectomy for contralateral ureteral metastasis 7 years after nephrectomy for renal cell carcinoma: A case report.

Contralateral ureteral metastasis after renal cell carcinoma (RCC) nephrectomy is uncommon. In such cases, a mass in the contralateral ureter needs to be differentiated from the primary ureteral tumor. If high grade primary ureteral tumor is found and total nephroureterectomy is performed, dialysis is introduced. In cases of metastasis of RCC, the kidney may be preserved by local treatment by partial ureterectomy. We report a case of contralateral ureteral metastasis after nephrectomy for right RCC. We underwent an originative method of pure laparoscopic partial ureterectomy and ureteral end-to-end anastomosis.

Laparoendoscopic single-site simple nephrectomy and reduced port procedure for inflammatory nonfunctioning kidney.

INTRODUCTION: To describe laparoendoscopic single-site simple nephrectomy and reduced port simple nephrectomy for inflammatory nonfunctioning kidney. CASE PRESENTATION: Case 1: a 58-year-old female with fever was referred to our hospital. Computed tomography demonstrated a markedly atrophic right kidney and mild hydronephrosis. Case 2: a 64-year-old male with a history of several intra-abdominal surgeries visited our hospital with a complaint of left back pain and fever. Computed tomography demonstrated left marked hydronephrosis, thinning of renal parenchyma, and duplicated inferior vena cava. After antibiotic treatment, transperitoneal reduced port simple nephrectomy and retroperitoneal laparoendoscopic single-site simple nephrectomy were performed in Case 1 and 2, respectively, because the function of the affected kidney was almost lost on renography. Although adhesion was slightly noted around the renal hilum in Case 1, neither conversion to laparotomy nor placement of additional ports was needed. CONCLUSION: Laparoendoscopic single-site simple nephrectomy and reduced port simple nephrectomy for inflammatory nonfunctioning kidney may be options for experienced laparoscopic surgeons.

Pure laparoscopic total ureterectomy for urothelial carcinoma that occurred in the ureteral stump after nephrectomy: A case report.

Primary carcinoma of the ureteral stump following a radical nephrectomy is rare, and it is even rarer that the cause of the nephrectomy is renal cell carcinoma (RCC). Treatment by complete ureterectomy with a bladder cuff is considered as the standard treatment. We report a case of a 70-year-old female with urothelial carcinoma with glandular differentiation that occurred in the ureteral stump after nephrectomy for left RCC. We performed a novel technique of pure laparoscopic resection of the ureteral stump with a bladder cuff.

Evaluating the Oncological Outcomes of Pure Laparoscopic Radical Nephroureterectomy Performed for Upper-Tract Urothelial Carcinoma Patients: A Multicenter Cohort Study Adjusted by Propensity Score Matching.

PURPOSE: To evaluate the oncological feasibility of pure laparoscopic radical nephroureterectomy (p-LRNU) for upper tract urothelial carcinoma (UTUC) compared with conventional LRNU (c-LRNU) using a propensity-adjusted multi-institutional collaboration dataset. METHODS: Among the 503 UTUC patients who underwent RNU, we identified 219 who underwent c-LRNU (laparoscopic nephrectomy with open bladder cuff resection) and 72 who underwent p-LRNU (dissecting the kidney, ureter, and bladder cuff under complete laparoscopy). We adopted a propensity score (PS) matching method to achieve homogeneity with respect to patient backgrounds. PS matching-adjusted Cox-regression analysis was performed to evaluate the risk factors that influenced oncological outcomes. RESULTS: Sixty-eight p-LRNU and 68 c-LRNU patients were matched. Overall, 51 (37.0%) developed intravesical recurrence (IVR), 21 (15.4%) had disease recurrence, and 20 (14.7%) died. Patients who underwent p-LRNU had a significantly shorter operation time and less blood loss than those who underwent c-LRNU. Although no significant differences in 3-year recurrence-free survival were found between the two methods, atypical recurrence sites were observed in the p-LRNU group, including the brain, sigmoid colon, vagina, and peritoneum. Regarding IVR, the 3-year IVR-free survival rate was 41.8% in the p-LRNU group, which was significantly lower than that in the c-LRNU group (66.6%, p = 0.004). Multivariate analysis demonstrated that a history of bladder cancer, ureteral cancer, and p-LRNU were independent risk factors for subsequent IVR. CONCLUSION: Although p-LRNU is less invasive, the current technique may increase the incidence of atypical disease recurrence and subsequent IVR due to extravesical and intravesical tumor dissemination.

Hand-assisted laparoscopic ileal ureter substitution for ureteral obstruction after right ureteral rupture: A case report.

Iatrogenic ureteral rupture is a serious complication. In the past, ileal ureter substitution was performed with open, laparoscopic, and robot-assisted procedure; however, there are problems with operation invasiveness and difficulty. We present a 72-year-old female whose ureter was completely injured at the ureteropelvic junction and torn longitudinally in full length at the time of transurethral lithotripsy. Although initially she had nephrostomy, we were able to internalize with hand-assisted laparoscopic ileal ureter substitution for obstruction over the full length of the ureter.

The pretreatment neutrophil-to-lymphocyte ratio is a novel biomarker for predicting clinical responses to pembrolizumab in platinum-resistant metastatic urothelial carcinoma patients.

PURPOSE: We investigated the relationship between pretreatment neutrophil-to-lymphocyte ratio (pre-NLR) levels just before the initiation of treatment with pembrolizumab and clinical outcomes in platinum-resistant metastatic urothelial carcinoma (UC) patients treated with pembrolizumab. METHODS: Our study population comprised 78 patients diagnosed with metastatic UC and treated with pembrolizumab after platinum-based chemotherapy at our institutions between December 2017 and April 2019. We examined the relationships between pre-NLR levels just before pembrolizumab treatment and clinical outcomes. A pre-NLR level of ≥3.35 was defined as elevated according to a calculation by a receiver-operating curve analysis. RESULTS: The high pre-NLR group consisted of 33 patients (42.3%). Overall, 29.5% of patients had a clinical response and the sum of the target lesion longest diameter was decreased in 18.8% of the high pre-NLR group, which was significantly lower than that in the low pre-NLR group (58.1%, P = 0.005). Six-month progression-free survival and cancer-specific survival rates for the high pre-NLR group were 9.1 and 58.0%, which were significantly lower than those for their counterpart (45.9 and 89.1%, P < 0.001 and P = 0.002, respectively). The pre-NLR level was an independent indicator of disease progression and cancer-specific death (P < 0.001 and P = 0.003). Furthermore, patients with a postpembrolizumab NLR level that had decreased ≥25% from the pre-NLR level had significantly lower disease progression and cancer-specific death rates than their counterparts (P = 0.01 and P = 0.022, respectively). CONCLUSIONS: Elevated pre-NLR may be a novel biomarker for identifying poor responders to pembrolizumab among platinum-resistant metastatic UC patients.

Appropriate timing for a biochemical evaluation after adrenalectomy for unilateral aldosterone-producing adenoma.

CONTEXT: The oversecretion of plasma aldosterone by unilateral aldosterone-producing adenoma (APA) can be cured by adrenalectomy. However, the time needed for the endocrine environment to normalize remains unclear. OBJECTIVE: To clarify adequate timing for a biochemical evaluation in unilateral APA patients after adrenalectomy. DESIGN AND PATIENTS: A total of 166 unilateral APA patients were retrospectively reviewed. We evaluated the plasma aldosterone concentration (PAC) (pg/mL), active renin concentration (ARC) (pg/mL), aldosterone-renin ratio (ARR; PAC/ARC), serum potassium concentration and estimated glomerular filtration rate (eGFR) at 1, 3 and 6 postoperation months (POM). RESULTS: PAC was significantly lower at 1POM than at presurgery (presurgery; 407.2, 1 POM; 90.0 pg/mL, P < .001). ARC did not increase from baseline at 1POM, but significantly increased at 3POM (presurgery; 4.43, 1POM; 4.87, 3POM; 11.3 pg/mL, P < .001). ARR significantly decreased at 1POM (presurgery; 146.9, 1 POM; 26.3, P < .001) although ARC did not increase at 1POM. Among the 34 patients who had hypokalaemia presurgery, it was resolved in 28 (82%) at 1POM and in all (100%) at 3POM. The biochemical outcomes at 1POM were 131 (79%) complete, 20 (12%) partial and 15 (9%) absent successes, while at 3POM, 147 (89%) were complete, 9 (5%) partial and 10 (6%) absent. Twenty-three (14%) patients were reclassified into different biochemical outcomes between 1 and 3POM, whereas only 5 (3%) changed between 3 and 6POM. CONCLUSION: The appropriate timing for a biochemical evaluation of unilateral APA patients treated with laparoscopic adrenalectomy appears to be 3 months or more after surgery.

Retroperitoneoscopic partial adrenalectomy for metachronous renal cell carcinoma metastasis to solitary adrenal gland.

Metastasectomy is a widely accepted treatment for renal cell carcinoma (RCC) metastasis, and is regarded as the most effective strategy for increasing the rate of cancer-specific survival. However, since bilateral synchronous or metachronous adrenal metastasis of RCC is extremely rare, a standard approach has yet to be established. Partial adrenalectomy may avoid lifelong hormonal supplementation and reduce the risk of Addisonian crisis. A 71-year-old man had a previous history of left nephrectomy and ipsilateral adrenalectomy for metachronous adrenal metastasis. Metachronous contralateral adrenal metastasis was detected 2 years after ipsilateral adrenalectomy, and he underwent retroperitoneoscopic partial adrenalectomy using a vessel sealing device. Although corticosteroid replacement therapy was not prophylactically performed, the patient did not exhibit any symptoms of hypocorticism. Nine months after the surgery, the patient remains well without steroid supplementation, and neither local recurrence nor metastasis has been detected. To the best of our knowledge, this is the first case report of laparoscopic partial adrenalectomy for RCC metastasis. The vessel sealing device was highly effective and suitable for laparoscopic partial adrenalectomy.

Laparoscopic management for a psoas abscess caused by migrated urolithiasis.

INTRODUCTION: To describe laparoscopic surgery for psoas abscess caused by migrated urolithiasis. CASE PRESENTATION: A 64-year-old female had renal stones in the right kidney for 5 years. She developed right back pain. Her body temperature was 37.4°C, and right costovertebral angle tenderness was detected. In blood examination, her C-reactive protein level was elevated. Computed tomography revealed that one stone had migrated into the right psoas muscle and caused psoas abscess. Another stone was detected in the renal parenchyma. Percutaneous drainage and antibiotic treatment were performed until her symptoms and inflammation improved. However, psoas abscess recurred after removal of the drainage tube. The migrated stone was laparoscopically removed after fenestration of psoas abscess, and laparoscopic nephrolithotomy was simultaneously performed for the other stone. CONCLUSION: To the best of our knowledge, this is the first case report of psoas abscess caused by migrated urolithiasis that was managed by minimally invasive surgery.

Establishment of the optimal follow-up schedule after radical prostatectomy.

PURPOSE: Monitoring the serum level of prostate specific antigen (PSA) is indispensable for surveillance after radical therapy, and the aim of this study was to establish the optimal follow-up schedule. MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological data of 1,010 consecutive patients who underwent radical prostatectomy. After excluding patients who received neoadjuvant or adjuvant therapy and those without a nadir PSA level<0.2ng/ml, the remaining 779 patients were enrolled. Biochemical recurrence (BCR) was defined as elevation of PSA to >0.2ng/ml. We investigated the PSA doubling time (PSA-DT) following BCR at various times after surgery. RESULTS: During a mean follow-up of 8.8 years, BCR occurred in 180/779 patients. The annual BCR rate was 6% in the first year after surgery, 6% between 1 and 2 years, 3% between 2 and 3 years, 3% between 3 and 5 years, and 2% at >5 years postoperatively. During these periods, the minimum PSA-DT after BCR was 1.6, 2.4, 3.1, 6.1, and 6.4 months, respectively. These minimum PSA-DTs were used to determine the optimal follow-up interval during each period after surgery. If the baseline level is 0.1ng/ml, PSA should be measured at approximately 3-month intervals for the first year, at 4-month intervals between 1 and 2 years, at 6-month intervals between 2 and 3 years, and annually thereafter to definitely detect BCR before the serum PSA level exceeds 0.4ng/ml. CONCLUSION: The PSA-DT following BCR varies according to the time after surgery. Our data on minimum PSA-DT values after BCR are useful for setting the optimal follow-up schedule.

Change of the 5α/5ß ratio of urinary steroid metabolites in benign prostatic hyperplasia patients treated with dutasteride.

BACKGROUND: The effects of the administration of dutasteride (DUT) on steroid metabolite pathways in BPH patients have not been examined. METHODS: Urine and blood samples as well as clinical parameters were prospectively collected after the administration of DUT to 60 BPH patients, and after its withdrawal in another set of 25 BPH patients. Urine samples were assessed using gas chromatography/mass spectrometry for the urinary steroid profile (USP), which simultaneously measures 63 steroid metabolites. We examined pharmacological changes in the 5α/5ß ratio of urinary metabolites and their relationships with clinical parameters in patients treated with DUT. RESULTS: The mean urinary androsterone/etiocholanolone (An/Et) ratio in sex-steroid pathways significantly decreased from 1.39 to 0.02 (p < 0.01). Urinary metabolites in other steroid pathways such as 5αTHF/5ßTHF in the glucocorticoid pathway and 5αTHB/5ßTHB in the mineralocorticoid pathway also significant decreased after the DUT treatment. As compared to baseline level, the mean An/Et ratios in patients with the withdrawal of DUT were 0.7%, 1.4%, 12.6%, and 82.4% at just before, one month, 3 months, and 6 months after the withdrawal of DUT, respectively. All other steroid pathways changed in a similar manner without the aggravation of urinary symptoms. The recovery ratio of An/Et in USP before and 3 months after the withdrawal of DUT correlated with the recovery ratio of serum PSA levels (ρ = 0.61, p < 0.01). CONCLUSION: Urinary 5α/5ß metabolites in all pathways were strongly suppressed after the administration of DUT for one month and the pharmacological effect of DUT prolonged even after withdrawal of DUT.

Factors influencing the operating time for single-port laparoscopic radical nephrectomy: focus on the anatomy and distribution of the renal artery and vein.

OBJECTIVE: It is considered that laparoscopic single-site surgery should be performed by specially trained surgeons because of the technical difficulty in using special instruments through limited access. We investigated suitable patients for single-port laparoscopic radical nephrectomy, focusing on the anatomy and distribution of the renal artery and vein. METHODS: This retrospective study was conducted in 52 consecutive patients who underwent single-port radical nephrectomy by the transperitoneal approach. In patients undergoing right nephrectomy, a 2-mm port was added for liver retraction. We retrospectively re-evaluated all of the recorded surgical videos and preoperative computed tomography images. The pneumoperitoneum time (PT) was used as an objective index of surgical difficulty. RESULTS: The PT was significantly shorter for right nephrectomy than left nephrectomy (94 vs. 123 min, P = 0.004). With left nephrectomy, dissection of the spleno-renal ligament to mobilize the spleen medially required additional time. Also, the left renal vein could only be divided after securing the adrenal, gonadal and lumbar veins. In patients whose renal artery was located cranial to the renal vein, PT tended to be longer than in the other patients (131 vs. 108 min, P = 0.070). In patients with a superior renal artery, the inferior renal vein invariably covered the artery and made it difficult to ligate the renal artery via the umbilical approach at the first procedure. CONCLUSIONS: These findings indicate that patients undergoing right nephrectomy in whom the renal artery is not located cranial to the renal vein are suitable for single-port laparoscopic radical nephrectomy.

The learning curve of laparoendoscopic single-site adrenalectomy: an analysis of over 100 cases.

BACKGROUND: Recently, laparoendoscopic single-site adrenalectomy (LESS-A) has been developed as an alternative treatment for adrenal tumors. Although LESS-A is more technically complex than conventional laparoscopic adrenalectomy, its learning curve and the factors associated with poor surgical outcomes are poorly understood. We analyzed the learning curve of LESS-A and attempted to identify risk factors associated with worse surgical outcomes. METHODS: We identified 103 patients who underwent LESS-A [performed by the same surgeon (A.M.)] from 2009 to 2015. The learning curve was analyzed using the moving average method (the 10-case moving average), and we assessed potential risk factors for a prolonged pneumoperitoneum time. RESULTS: The learning curve stabilized at 30 cases. The cases were divided into two groups, the learning stage (LS) (cases 1-29) and master stage (MS) (cases 30-103) groups. The percentage of females and the frequency of previous abdominal surgery were higher in the LS group (p = 0.022 and 0.001, respectively). In the LS group, the mean pneumoperitoneum time was 92 ± 35 min, which was significantly longer than the equivalent value for the MS group (55 ± 18 min, p < 0.001). In the LS group, univariate analysis revealed that tumor size (≥50 mm) and the visceral fat area (VFA)/total fat area (TFA) ratio (≥0.49) were significantly associated with a prolonged pneumoperitoneum time (p = 0.046 and 0.046, respectively). In the multivariate analysis, tumor size and the VFA/TFA ratio were confirmed to be associated with a prolonged pneumoperitoneum time (p = 0.029 and 0.029, odds ratio 20.83 and 20.83, respectively). On the other hand, none of the examined factors were found to be associated with a prolonged pneumoperitoneum time in the MS group. CONCLUSIONS: LESS-A was performed safely in most cases. However, surgeons who are learning the LESS-A procedure need to pay attention to tumor size and visceral obesity.

Relationship Between Increased Expression of the Axl/Gas6 Signal Cascade and Prognosis of Patients with Upper Tract Urothelial Carcinoma.

PURPOSE: Axl, which is in the TAM family of receptor tyrosine kinases, and its ligand, growth arrest-specific gene 6 (Gas6), have been associated with worse prognoses after the surgical treatment of some types of cancers. We herein investigated the biological significance of the protein expression of Axl and Gas6 on the outcomes of patients with upper tract urothelial carcinoma (UTUC). METHODS: The protein expression of Axl and Gas6 was evaluated by immunohistochemistry, and their relationships with clinicopathological features were investigated in surgical specimens obtained from 161 patients who had been surgically treated for UTUC. RESULTS: Axl labeling was strong in 67 of 161 (42 %) cases, while Gas6 labeling was strong in 72 of 161 (45 %) cases. The strong expression of Axl correlated with that of Gas6. A high pathological stage (p = 0.009), strong expression of Gas6 (p = 0.038), and strong expression of Axl (p = 0.016) were independent factors for predicting worse cancer-specific survival (CSS). In a subgroup analysis of patients with pT < 2 (N = 53), no significant difference in CSS was observed between patients weakly and strongly expressing Axl/Gas6. In contrast, a subgroup analysis of patients with pT ≥ 2 (N = 108) revealed that the expression levels of Axl and Gas6 correlated with CSS. CONCLUSION: The protein expression of Axl and its ligand Gas6 may be a useful indicator for a worse clinical outcome in UTUC patients, especially patients with pT ≥ 2, who underwent radical nephroureterectomy.

A case of paraneoplastic liver dysfunction with elevated serum interleukin-6 in clinically localized renal cell carcinoma.

We report a case of paraneoplastic liver dysfunction associated with a renal cell carcinoma, which disappeared after surgery. A 62-year-old male presented with fatigue and weight loss. The most prominent laboratory abnormality was elevated alkaline phosphatase, C-reactive protein, and interleukin-6 while normal aminotransferases. Computed tomography scan revealed a solid mass in the left kidney. A left radical nephrectomy was performed. After the surgery, biochemical abnormalities returned to normal.

Comparison of continence outcomes of early catheter removal on postoperative day 2 and 4 after laparoscopic radical prostatectomy: a randomized controlled trial.

BACKGROUND: The optimal timing of catheter removal following laparoscopic radical prostatectomy (LRP) has not yet been determined. This prospective study was designed to compare the efficacy and safety of catheter removal on postoperative day (POD) 2 versus POD 4 after LRP and its impact on urinary continence outcomes. METHODS: One hundred and thirteen patients underwent LRP and were prospectively randomized into two groups: group 1 (n = 57) had the urinary catheter removed on POD 2 while group 2 (n = 56) had the catheter removed on POD 4. The urine loss ratio (ULR) was defined as the weight of urine loss in the pad divided by the daily micturition volume. Continence was defined as a pad-free status. RESULTS: No significant differences were observed in clinical features between groups 1 and 2. Acute urinary retention (AUR) after catheter removal occurred in 21 patients (18.6%) (13 (22.8%) in group 1 and 8 (14.3%) in group 2 (p = 0.244). The first-day mean ULR values were 1.16 ± 4.95 in group 1 and 1.02 ± 3.27 in group 2 (p = 0.870). The last-day mean ULR values were 0.57 ± 1.60 in group 1 and 2.78 ± 15.49 in group 2 (p = 0.353). Continence rates at 3, 6, 9, and 12 months were 21.8, 41.1, 58.0, and 71.4% in group 1 and 34.5, 66.0, 79.2, and 83.7% in group 2 (p = 0.138, 0.009, 0.024, and 0.146, respectively). In AUR cases, continence rates at 3, 6, 9, and 12 months were 0, 23.1, 38.5, and 54.5% in group 1 and 37.5, 75.0, 87.5, and 87.5% in group 2 (p = 0.017, 0.020, 0.027, and 0.127, respectively). A multivariate analysis identified AUR after catheter removal on POD 2 as the only predictive factor for incontinence 6 and 9 months after LRP (p = 0.030 and 0.018, respectively). CONCLUSIONS: Our results demonstrated that early catheter removal on POD 2 after LRP may increase the risk of incontinence. TRIAL REGISTRATION: The study was registered as Clinical trial: (UMIN000014944); registration date: 12 March 2012.

Visceral to total obesity ratio and severe hydronephrosis are independently associated with prolonged pneumoperitoneum operative time in patients undergoing laparoscopic radical nephroureterectomy for upper tract urothelial carcinoma.

BACKGROUND: Our aim was to evaluate the effect of visceral obesity and impact of severe hydronephrosis on surgical complexity in patients undergoing laparoscopic radical nephroureterectomy (LRNU). METHODS: From January 2000 to December 2013, 169 patients underwent radical nephroureterectomy at our institution. We retrospectively reviewed the medical records of 70 patients who underwent LRNU. We measured total fat area (TFA) and visceral fat area (VFA) at the level of the umbilicus using computed tomography. We defined accumulated visceral fat distribution as a VFA/TFA ratio ≥0.45. Ipsilateral hydronephrosis was graded from 0 to 4 by two uro-radiologists blinded to the clinical outcomes. RESULTS: Among the 70 patients, VFA/TFA ratio was ≥0.45 in 40 patients (57.1%) and 28 (40.0%) had severe hydronephrosis (grade 3 or greater). Patients with a VFA/TFA ratio ≥0.45 had significantly longer pneumoperitoneum and total operation times compared to their counterparts (p = 0.047 and p = 0.002, respectively). Patients with severe hydronephrosis had significantly longer pneumoperitoneum and total operative times compared to their counterparts (p = 0.006 and p = 0.002, respectively). Multivariate logistic regression analysis showed that a high VFA/TFA and severe hydronephrosis were independent predictive factors for prolonged pneumoperitoneum (p = 0.048, HR = 2.90; p = 0.015, HR = 3.82, respectively) and total operative times (p < 0.001, HR = 18.7; p = 0.003, HR = 10.7; respectively). Other pre-clinical factors such as age, gender, BMI, clinical stage, tumor size, location, laterality, degree of perinephric stranding, and surgical procedure did not affect the operation times. CONCLUSION: The present data indicated that the visceral type of adipose accumulation and presence of severe hydronephrosis could provide preoperative information on the degree of technical difficulty associated with LRNU.

Intravesical dual PI3K/mTOR complex 1/2 inhibitor NVP-BEZ235 therapy in an orthotopic bladder cancer model.

NVP-BEZ235 is an inhibitor of both phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin complex 1/2 (mTORC1/2), and its antitumor activity is expected to be higher than that of mTORC1 inhibitors because it inhibits the upregulation of pAkt through mTORC2. We examined the efficacy of intravesical NVP-BEZ235 therapy in the treatment of bladder cancer using an orthotopic bladder cancer model. The cytotoxic effects of various concentrations of NVP-BEZ235 in MBT-2 cells were examined using a WST assay. The expression of pAkt, pS6 and p4EBP1 was evaluated in MBT-2 cells treated with NVP-BEZ235 using western blotting. Orthotopic models were established by implanting MBT-2 cells into the bladders of female C3H/He mice. We assigned C3H/He mice to 2 groups: a control group treated with vehicle control (n=15), and a group intravesically administered 40 µM (18.78 mg/l) of NVP-BEZ235 (n=15). NVP-BEZ235 inhibited the viability of MBT-2 cells in a dose-dependent manner. Furthermore, the expression of pAkt, pS6, and p4EBP1 was inhibited in NVP-BEZ235-treated MBT-2 cells. Bladder weights were significantly lower in the NVP-BEZ235-treated group than in the control group (P<0.05). An analysis of the tumor tissues revealed that the NVP-BEZ235 treatment strongly reduced pAkt, pS6 and p4EBP1 levels. An immunohistochemical analysis showed that NVP-BEZ235 significantly inhibited the expression of pS6. Intravesically administered NVP-BEZ235 exerted significant antitumor effects in the orthotopic bladder cancer model by inhibiting the PI3K/Akt/mTOR pathway. The intravesical instillation of a dual PI3K/mTORC1/2 inhibitor may represent a novel therapy for the treatment of bladder cancer.