Botulinum Toxin A for Bladder Pain Syndrome/Interstitial Cystitis

Botulinum neurotoxin A (BoNT-A), derived from Clostridium botulinum, has been used clinically for several diseases or syndrome including chronic migraine, spasticity, focal dystonia and other neuropathic pain. Chronic pelvic or bladder pain is the one of the core symptoms of bladder pain syndrome/interstitial cystitis (BPS/IC). However, in the field of urology, chronic bladder or pelvic pain is often difficult to eradicate by oral medications or bladder instillation therapy. We are looking for new treatment modality to improve bladder pain or associated urinary symptoms such as frequency and urgency for patients with BPS/IC. Recent studies investigating the mechanism of the antinociceptive effects of BoNT A suggest that it can inhibit the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. In this review, we will examine the evidence supporting the use of BoNTs in bladder pain from basic science models and review the clinical studies on therapeutic applications of BoNT for BPS/IC

The effect of tumor location on oncologic outcomes in patients with upper urinary tract urothelial carcinoma stratified by pathologic stage

Objectives: The aim of this study was to investigate the effect of tumor location on oncologic outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) stratified according to pathologic stage. ;Material and methods: Between January 1996 and March 2009, 503 patients with UTUC were enrolled who had undergone radical nephroureterectomies and had no nodal or distal metastases. Preoperative chemotherapy or radiation therapy was not administered to any study patient. Clinicopathologic patient characteristics were obtained and used to analyze recurrence-free survival (RFS), cancer-specific survival, and overall survival with the Cox proportional hazards model. ;Results: During the median follow-up of 52 months, patients with pathologic tumor (pT) stage 3 ureteral tumors had a shorter duration of RFS compared with those with pT3 renal pelvis tumors (5-y RFS: 50% and 71%, P = 0.047). There was no prognostic relevance to the tumor location in pTa/Tis/T1 and pT2 diseases. RFS and cancer-specific survival were significantly shorter in duration in pT3 ureteral disease compared with pT2 diseases (P < 0.001 and P = 0.028). No differences were found in oncologic outcomes between pT3 renal pelvic and pT2 diseases. The presence of pT3 ureteral tumors actually increased the risks of disease recurrence (hazard ratio [HR] = 7.82, P < 0.001), cancer-specific death (HR = 5.08, P < 0.001), and overall mortality (HR = 3.25, P = 0.031). ;Conclusions: Patients with UTUC and pT3 ureteral tumors had an increased risk of disease recurrence and cancer-specific death. These results underscore the need for close follow-up and the consideration of adjuvant chemotherapy for patients with pT3 ureteral cancer. (C) 2016 Elsevier Inc. All rights reserved

針對各種膀胱病變之腹腔鏡部份膀胱切除術

To present our initial experience with laparoscopic partial cystectomy ( LPC) in selected patients with various bladder pathologies. Between December 2004 and April 2006, four patients had LPC at our centre (mean age 52 years, range 35- 70); the transperitoneal approach was used for three and a pre-peritoneal approach for one. The surgical procedures used sequentially included transurethral incision around the lesion, laparoscopic excision of the lesion (partial cystectomy) and intracorporeal suturing. Laparoscopic pelvic lymphadenectomy was also used for the two patients with malignancy. All operations proceeded smoothly; the bladder pathologies included one bladder endometriosis, one bladder leiomyoma, one urothelial carcinoma within the bladder diverticulum and one urachal adenocarcinoma. The mean (range ) operative duration was 197.5 (120-300) min, the estimated blood loss 70 (50-100) mL, the hospital stay 6.75 (5-9) days , and duration of Foley catheterization 7.25 (6-9) days. No open conversion was required and no patient had peri- operative complications. The surgical margins were free of cancer and the dissected lymph nodes were negative in those two patients with bladder malignancy. LPC is safe and feasible in selected patients with various bladder pathologies

Bradykinin promotes vascular endothelial growth factor expression and increases angiogenesis in human prostate cancer cells

Prostate cancer is the most commonly diagnosed malignancy in men and shows a tendency for metastasis to distant organs. Angiogenesis is required for metastasis. Bradykinin (BK) is an inflammatory mediator involved in tumor growth and metastasis, but its role in vascular endothelial growth factor (VEGF) expression and angiogenesis in human prostate cancer remains unknown. The aim of this study was to examine whether BK promotes prostate cancer angiogenesis via VEGF expression. We found that exogenous BK increased VEGF expression in prostate cancer cells and further promoted tube formation in endothelial progenitor cells and human umbilical vein endothelial cells. Pretreatment of prostate cancer with B2 receptor antagonist or small interfering RNA (siRNA) reduced BK-mediated VEGF production. The Akt and mammalian target of rapamycin (mTOR) pathways were activated after BK treatment, and BK-induced VEGF expression was abolished by the specific inhibitor and siRNA of the Akt and mTOR cascades. BK also promoted nuclear factor-kappa B (NF-kappa B) and activator protein 1 (AP-1) activity. Importantly, BK knockdown reduced VEGF expression and abolished prostate cancer cell conditional medium-mediated angiogenesis. Taken together, these results indicate that BK operates through the B2 receptor, Akt, and mTOR, which in turn activate NF-kappa B and AP-1, activating VEGF expression and contributing to angiogenesis in human prostate cancer cells. (C) 2013 Elsevier Inc. All rights reserved

Surgical Management in Enterovesical Fistula in Crohn Disease at a Single Medical Center

Crohn disease is a chronic, transmural, inflammatory disease of the gastrointestinal tract with unknown etiology. It can affect any part of the gastrointestinal tract and may cause fistula, stricture, or abscess formation with disease progression. The preoperative diagnosis and definite management of this rare complication are challenges for physicians, urologists, and surgeons

Intermediate-Term Oncological Outcomes of Hand-Assisted Laparoscopic Versus Open Bilateral Nephroureterectomy for Dialysis and Kidney Transplant Patients with Upper Urinary Tract Urothelial Carcinoma

Purpose: To compare the outcomes of hand-assisted laparoscopic bilateral nephroureterectomy (HALBNU) for dialysis and kidney transplant patients with clinically localized upper urinary tract urothelial carcinoma (UUT-UC ) with those achieved by open bilateral nephroureterectomy ( OBNU). Materials and Methods: Between 1995 and 2006, 49 patients under dialysis or after kidney transplantation underwent simultaneous bilateral nephroureterectomy for clinically presumed localized UUT-UC at our institute. Of those, 33 underwent HALBNU and 16 received conventional open surgery. Perioperative and pathological data and oncological outcomes were collected by chart review. Bladder recurrence, metastasis, and cancer -specific and overall survival were analyzed and compared between both groups. Results: The median follow-up for HALBNU and OBNU group was 35 and 46 months, respectively. Totally, 40 patients were identified to have pathologically confirmed urothelial carcinoma of upper urinary tract. HALBNU group was associated with less blood loss, earlier bowel recovery, less narcotic use, shorter hospital stay, and earlier convalescence. The operative time and complication rate were comparable between the two groups. There was no open conversion in the HALBNU group. The two groups were similar in regard to bladder recurrence rate. The overall, cancer- specific, and bladder-recurrence-free survival were also equivalent between the HALBNU and OBNU group (all p>0.05). Conclusion: In dialysis and kidney transplant patients with localized UUT-UC, simultaneous bilateral nephroureterectomy with hand-assisted laparoscopic approach offered less perioperative morbidity and, most importantly, comparable intermediate-term oncological and survival results when compared with its open counterpart. A longer follow-up is required to demonstrate the oncological efficacy of this minimally invasive procedure

Diabetes mellitus with poor glycemic control increases bladder cancer recurrence risk in patients with upper urinary tract urothelial carcinoma

Background The association of diabetes mellitus and bladder cancer recurrence following radical nephroureterectomies (RNUs) in patients with upper urinary tract urothelial carcinoma (UTUC) was investigated. ;Methods Between January 1996 and March 2009, 538 patients with UTUC who received RNU and had no previous bladder cancer histories were enrolled. The clinicopathological characteristics were obtained and used for the analysis of metachronous bladder recurrence by using Cox proportional hazard model. ;Results The diabetic patients (N=104, 19.3%) were elderly (72 vs 67 years, p<0.001) and had more hypertension (56.7 vs 34.5%, p<0.001) as compared with non-diabetic patients. There was no significant difference in the rest of clinicopathological characteristics between patient groups. During the median follow-up duration of 51 months, bladder recurrences were discovered in 47.1 and 33.1% of diabetic and non-diabetic patients with UTUC, respectively. Poorly controlled diabetic patients (HbA(1c) >= 7.0%) exhibited a shorter duration of bladder cancer recurrence-free survival as compared with those with good glycemic controlled diabetes mellitus and without diabetes mellitus (log-rank test, p < 0.001 and < 0.001, respectively). In the multivariate analysis, male gender [hazard ratio (HR) = 1.67, p = 0.017], ureteral tumour (HR = 1.61, p = 0.020), end-stage renal disease (HR = 2.09, p = 0.030) and diabetes mellitus with poor glycemic control (HR = 2.10, p < 0.018) independently predicted bladder recurrence after RNU. ;Conclusions Diabetes mellitus with poor glycemic control (HbA(1c) >= 7.0%) increases the risk of subsequent bladder cancer recurrence. These results underscore the need for intensive glycemic control and close follow-up for diabetic patients. Copyright (C) 2014 John Wiley & Sons, Ltd

Bradykinin promotes vascular endothelial growth factor expression and increases angiogenesis in human prostate cancer cells

Prostate cancer is the most commonly diagnosed malignancy in men and shows a tendency for metastasis to distant organs. Angiogenesis is required for metastasis. Bradykinin (BK) is an inflammatory mediator involved in tumor growth and metastasis, but its role in vascular endothelial growth factor (VEGF) expression and angiogenesis in human prostate cancer remains unknown. The aim of this study was to examine whether BK promotes prostate cancer angiogenesis via VEGF expression. We found that exogenous BK increased VEGF expression in prostate cancer cells and further promoted tube formation in endothelial progenitor cells and human umbilical vein endothelial cells. Pretreatment of prostate cancer with B2 receptor antagonist or small interfering RNA (siRNA) reduced BK-mediated VEGF production. The Akt and mammalian target of rapamycin (mTOR) pathways were activated after BK treatment, and BK-induced VEGF expression was abolished by the specific inhibitor and siRNA of the Akt and mTOR cascades. BK also promoted nuclear factor-kappa B (NF-kappa B) and activator protein 1 (AP-1) activity. Importantly, BK knockdown reduced VEGF expression and abolished prostate cancer cell conditional medium-mediated angiogenesis. Taken together, these results indicate that BK operates through the B2 receptor, Akt, and mTOR, which in turn activate NF-kappa B and AP-1, activating VEGF expression and contributing to angiogenesis in human prostate cancer cells. (C) 2013 Elsevier Inc. All rights reserved