Bladder lesions as incidental findings during transurethral resection of the prostate: prevalence, diagnosis, and pathological findings.

PURPOSE: The purpose of this study was to determine the prevalence of bladder lesions diagnosed during transurethral resection of the prostate (TURP), to identify the associated risk factors, and to correlate the macroscopic descriptions with the pathological findings. METHODS: This was a single-center retrospective case series conducted at a hospital in the city of São Paulo, Brazil. We reviewed the medical and surgical records of patients who underwent TURP between January 2012 and December 2017. RESULTS: The final sample comprised 513 patients, with a mean age of 70.8 years. Bladder lesions were identified during TURP in 109 (21.2%) of the patients, and 90 of those lesions were submitted for pathological examination. The most common macroscopic finding was bullous edema, which was seen in 57 (63.3%) of the 90 lesions examined. The pathological analysis revealed chronic cystitis in 61 lesions (67.8%) and malignant lesions in 16 (17.8%). Of the 57 lesions described as bullous edema, 5 (8.8%) were found to be malignant. CONCLUSIONS: Alterations in the bladder mucosa appear to be more common among elderly patients who use an indwelling urinary catheter for a prolonged period and among patients with recurrent urinary tract infections. In addition, the risk of a bladder lesion being malignant is apparently higher in current and former smokers than in never smokers. Our findings suggest that at-risk patients should undergo biopsy or resection of incidental bladder lesions even if those lesions seem to be benign, due to the low level of agreement between the visual analysis and the pathological examination.

Uroprotective mechanisms of natural products against cyclophosphamide-induced urinary bladder toxicity: A comprehensive review.

One of the widely used anticancer drugs for the treatment of various neoplasms is cyclophosphamide (CYP). The inactive prodrug CYP is metabolized by cytochrome P450 enzyme into active metabolites, phosphoramide mustard and acrolein. The accumulation of acrolein metabolite inside the urothelium results in hemorrhagic cystitis (HC) which is a urotoxic adverse effect associated with the use of CYP. To counteract the occurrence of HC induced by CYP, Mesna is usually used, with allergic reactions reported in some cases. Therefore, several natural products have drawn much attention as alternative safe therapies to reduce the urotoxicity produced from the use of CYP. This review will focus on certain uroprotective mechanisms related to some medicinal plants that are used to ameliorate the CYP-induced urotoxicity in experimental models. The mechanisms involving oxidative stress, inflammation, immune system, apoptosis, DNA fragmentation, uroplakins, purinergic signaling and muscarinic receptors, and CytoP450 metabolism are discussed.

Curcumin ameliorates cisplatin-induced cystopathy via activating NRF2 pathway.

OBJECTIVES: The present work evaluated preventive effect of curcumin on cisplatin-induced bladder cystopathy. METHODS: Fifteen female rats were divided into (i) Control group administered with physiological saline solution for 5 days; (ii) Cis-P group injected with cisplatin (6 mg/kg); and (iii) Cis-Cur group given cisplatin (6 mg/kg) with curcumin for 5 consecutive days. The function of bladder was measured by means of urodynamic analysis. Furthermore, hematoxylin-eosin staining and Masson trichrome staining were performed for morphological analysis. The cell apoptosis was evaluated through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and flow cytometry. The expression of nerve growth factor (NGF), NF-E2-related factor 2, and hemeoxygenase-1 (HO-1) levels were measured through Western blotting. RESULTS: Urodynamic assay and histopathological manifestations revealed that curcumin ameliorated the bladder dysfunction induced by cisplatin. The level of cisplatin-induced apoptosis in the bladder decreased following curcumin treatment. Also, the increased protein expression of NGF indicated that the curcumin could offer neuroprotection for bladder against cisplatin. Curcumin also activated NRF2, and elevated the expression of HO-1, but curcumin could not rescue cisplatin-induced apoptosis in the cell lines with knockdown of NRF2. CONCLUSIONS: Taken together, the results of this paper showed that curcumin could ameliorate cisplatin-induced cystopathy and inhibit the apoptosis of bladder cell in cisplatin-treated rats. This may be attributed to curcumin's broad biological functions, particularly antioxidant effect, and to its ability to activate the NRF2 protein.

Toxic effects of 4-methylthio-3-butenyl isothiocyanate (Raphasatin) in the rat urinary bladder without genotoxicity.

We recently reported that 4-methylthio-3-butenyl isothiocyanate (MTBITC) exerts chemopreventive effects on the rat esophageal carcinogenesis model at a low dose of 80 ppm in a diet. In contrast, some isothiocyanates (ITCs) have been reported to cause toxic effects, promotion activity, and/or carcinogenic potential in the urinary bladder of rats. In the present study, we investigated whether MTBITC had toxic effects in the urinary bladder similar to other ITCs, such as phenethyl ITC (PEITC). First, to examine the early toxicity of MTBITC, rats were fed a diet supplemented with 100, 300 or 1000 ppm MTBITC for 14 days. Treatment with 1000 ppm MTBITC caused increased organ weights and histopathological changes in the urinary bladder, producing lesions similar to those of 1000 ppm PEITC. In contrast, rats treated with 100 or 300 ppm MTBITC showed no signs of toxicity. Additionally, we performed in vivo genotoxicity studies to clarify whether MTBITC may exhibit a carcinogenic potential through a genotoxic mechanism in rats. Rats were treated with MTBITC for 3 days at doses of 10, 30 or 90 mg kg-1 body weight by gavage, and comet assays in the urinary bladder and micronucleus assays in the bone marrow were performed. No genotoxic changes were observed after treatment with MTBITC at all doses. Overall, these results suggested that the effects of MTBITC in the rat urinary bladder are less than those of PEITC, but that MTBITC could have toxic effects through a nongenotoxic mechanism in the urinary bladder of rats at high doses. Copyright © 2016 John Wiley & Sons, Ltd.

Does visualisation during urethrocystoscopy provide pain relief? Results of an observational study.

BACKGROUND: To measure the effects of real-time visualisation during urethrocystoscopy on pain in patients who underwent ambulatory urethrocystoscopy. METHODS: An observational study was designed. From June 2012 to June 2013 patients who had ambulatory urethrocystoscopy participated in the study. In order to measure pain perception we used a numeric rating scale (NRS) 0 to 10. Additional data was collected including gender, reason for intervention, use of a rigid or a flexible instrument and whether the patient had had urethrocystoscopy before. RESULTS: 185 patients were evaluated. 125 patients preferred to watch their urethrocystoscopy on a real-time video screen, 60 patients did not. There was no statistically relevant difference in pain perception between those patients who watched their urethrocystoscopy on a real-time video screen and those who did not (p = 0.063). However, men who were allowed to watch their flexible urethrocystoscopy experienced significantly less pain, than those who did not (p = 0.007). No such effects could be measured for rigid urethrocystoscopy (p = 0.317). Furthermore, women experienced significantly higher levels of pain during the urethrocystoscopy than men (p = 0.032). CONCLUSIONS: Visualisation during urethrocystoscopy procedures in general does not significantly decrease pain in patients. Nevertheless, men who undergo flexible urethrocystoscopy should be offered to watch their procedure in real-time on a video screen. To make urethrocystoscopy less painful for both genders, especially for women, should be subject to further research.

The protective effect of Moringa oleifera leaves against cyclophosphamide-induced urinary bladder toxicity in rats.

Cyclophosphamide (CP), an alkylating antineoplastic agent is widely used in the treatment of solid tumors and B-cell malignant disease. It is known to cause urinary bladder damage due to inducing oxidative stress. Moringa oleifera (Mof) is commonly known as drumstick tree. Moringa leaves have been reported to be a rich source of ß-carotene, protein, vitamin C, calcium, and potassium. It acts as a good source of natural antioxidants; due to the presence of various types of antioxidant compounds such as ascorbic acid, flavonoids, phenolics and carotenoids. The aim of this work was to test the possible antioxidant protective effects of M. oleifera leaves against CP induced urinary bladder toxicity in rats. Female Wister albino rats were divided into 4 groups. Group I served as control, received orally normal saline, group II received a single dose CP 100mg/kg intraperitoneally, group III and VI both received orally hydroethanolic extract of Mof; 500 mg/kg and 1000 mg/kg respectively daily for a week, 1h before and 4h after CP administration. Rats were sacrificed 24h after CP injection. The bladder was removed, sectioned, and subjected to light, transition electron microscopic studies, and biochemical studies (measuring the parameter of lipid peroxidation; malondialdehyde along with the activities of the antioxidant enzyme reduced glutathione). The bladders of CP treated rats showed ulcered mucosa, edematous, hemorrhagic, and fibrotic submucosa by light microscopy. Ultrastructure observation showed; losing large areas of uroepithelium, extended intercellular gaps, junction complexes were affected as well as damage of mitochondria in the form of swelling and destruction of cristae. Biochemical analysis showed significant elevation of malondialdhyde, while reduced glutathione activity was significantly lowered. From the results obtained in this work, we can say that Moringa leaves play an important role in ameliorating and protecting the bladder from CP toxicity.

Tinospora cordifolia ameliorates urotoxic effect of cyclophosphamide by modulating GSH and cytokine levels.

Cyclophosphamide (CP) is a commonly used anti-cancer drug which causes toxicity by its reactive metabolites. In this study we investigated the effect of Tinospora cordifolia on urotoxicity induced by acute dose of CP using Swiss albino mice model. Administration of an alcoholic extract of the plant T. cordifolia (Family: Menispermaceae) (200 mg/kg i.p.) for 5 days reduced CP (1.5 mmol/kg body wt. i.p.) induced urotoxicity as evident from the morphological analysis of bladder, decreased the relative bladder and liver weights and also decreased level of urea nitrogen and protein in blood as well as urine. Severely inflamed and dark coloured urinary bladders of the CP alone treated animals were found to be normalized by the treatment of T. cordifolia. GSH content, which was drastically reduced by CP administration in both bladder and liver was enhanced by treatment with T. cordifolia. Histopathological analysis of the bladder of CP alone-treated group showed severe necrotic damage where as the T. cordifolia-treated group showed normal bladder architecture. The lowered levels of cytokines IFN-γ, IL-2, after CP treatment were found to be increased in treated animals. At the same time the level of pro-inflammatory cytokine TNF-α, which was elevated during CP administration, was significantly reduced by extract administration. This study clearly demonstrates uroprotective role of T. cordifolia from CP induced toxicities by modulating GSH and pro-inflammatory cytokine levels.

The enhancing effect of the antioxidant N-acetylcysteine on urinary bladder injury induced by dimethylarsinic acid.

Dimethylarsinic acid (DMA(V)), the major excreted metabolite of inorganic arsenic, is carcinogenic to the rat urinary bladder. Oxidative stress has been proposed as one possible mechanism of DMA(V)-induced carcinogenesis. The authors determined whether the antioxidant N-acetylcysteine (NAC) modifies DMA(V)-induced urinary bladder injury in rats. The treatment solutions--DMA(V) at 10 mg/kg, NAC at 90 or 1.6 mg/kg (high or low dose, respectively), and their combination--were intravesically instilled into female F344 rats over two hours under pentobarbital anesthesia. The treatment was conducted twice with an interval of three days. All animals were euthanized one day after the second treatment. NAC (low dose) alone did not induce histopathological changes or increase 5-bromo-2'-deoxyuridine (BrdU) labeling index in urothelial cells. Both DMA(V) and NAC (high dose) induced a weak neutrophil infiltration and an increase in the BrdU labeling index; these pathological changes were enhanced by the combined treatment of DMA(V) and NAC (high or low dose). Increased oxidative stress and urothelial cell hyperplasia with evidence of activated p44/42 MAPK (ERK1/2) and cyclin D1 were found in the DMA(V) and NAC (high dose) cotreated group. These results suggest that cotreatment with NAC enhanced DMA(V)-induced urinary bladder injury and that the effects may be mediated by excess oxidative stress and ERK signaling.

Chronic sacral nerve stimulation prevents detrusor structural and functional changes associated with bladder outlet obstruction--a rat model.

AIMS: Bladder outlet obstruction (BOO) can mediate structural and functional detrusor changes, which can lead to bothersome lower urinary tract symptoms. We investigate if sacral nerve stimulation (SNS) can prevent these structural and functional changes in a rat model of BOO. METHODS: 24 female Sprague-Dawley rats (250 gm) were divided into 4 groups: control (CTRL), BOO, SNS, and both (BOO/SNS). BOO was achieved by partially occluding the proximal urethra. SNS involved stimulating the S1-S4 dorsal roots with a unipolar S1 lead, 8 hours daily. Urodynamics were performed at baseline and after 6 weeks. Bladders were harvested, stained, and scored for detrusor hypertrophy and fibrosis (scale = 1-5). RESULTS: BOO caused an increase in mean voiding pressure (P(det) = 35 +/- 2 mmHg vs. 23 +/- 1 mmHg, p = 0.02), an increase in mean bladder capacity (C = 1230 +/- 250 microl vs. 484 +/- 60 microl, p = 0.03), and a decrease in mean volume at first non-voiding contraction (67 +/- 16 microl vs. 110 +/- 24 microl, p = 0.02) compared to CTRL. Addition of SNS neither significantly affected P(det) (30 +/- 3 mm Hg vs. 35 +/- 2 mmHg, p = 0.2), nor C (630 +/- 90 microl vs. 1230 +/- 250 microl, p = 0.06) compared to BOO, but eliminated non-voiding contractions. Detrusor hypertrophy and fibrosis were both significantly greater in BOO vs. CTRL and vs. BOO/SNS. CONCLUSIONS: Partial BOO caused functional and structural changes in the rat bladder. SNS in obstructed rats prevents these alterations, without adversely affecting detrusor contractility.

[Melanosis of the urinary bladder--a case report with 10 years of follow-up and review of literature]. / Melanose der Harnblase--Fallbericht mit Langzeitverlauf über 10 Jahre und Literaturübersicht.

INTRODUCTION: Extradermal melanotic lesions are found predominantly in the oral cavity, colon or conjunctiva, and by far less frequently in other organs. We report for the first time a case of solitary melanosis of the urinary bladder with a follow-up of more than 10 years. CASE REPORT: A 48-year old man presented with symptoms of frequency, urge incontinence, obstructive voiding symptoms and nocturia. On urethrocystoscopy under general anaesthesia, melanosis of the bladder with visibly reduced bladder capacity was diagnosed and confirmed on biopsy. The patient was treated for his micturation problems with alpha-blockers, intravesical electrostimulation and GAG-substitution therapy, without success. The chronic progression of bladder symptoms and shrinkage eventually led to cystoprostatectomy and bladder replacement by an orthotopic ileal neobladder, 10 years after primary diagnosis. CONCLUSION: The very low number of reported cases accounts for the lack of management guidelines for this disease. Symptomatic treatment as well as repeated cystoscopic monitoring are logical therapeutic recommendations. Since the development of malignant disease can only be ruled out microscopically, repeated biopsies or prophylactic cystectomy need to be considered.

Anaplastic lymphoma kinase (ALK 1) staining and molecular analysis in inflammatory myofibroblastic tumours of the bladder: a preliminary clinicopathological study of nine cases and review of the literature.

Inflammatory myofibroblastic tumours (IMFT) may arise at any anatomical site, including lung, soft tissues, retroperitoneum and bladder. Although morphologically similar, these lesions encompass a spectrum of entities with differing aetiology, ranging from reactive/regenerative proliferations to low-grade neoplasms with a risk of local recurrence, but no significant metastatic potential. Vesical IMFT usually presents as a polypoid mass with a pale firm cut surface and can be of considerable size, mimicking a malignant tumour clinically and radiologically. Its good outcome, however, warrants conservative surgical excision, emphasising the importance of identification and distinction from malignant tumours of the bladder that may require more radical surgery and/or adjuvant therapy. We conducted a preliminary retrospective, comparative immunocytochemical study of 20 bladder tumours, including nine IMFTs, five spindle cell (sarcomatoid) carcinomas, two rhabdomyosarcomas, two leiomyosarcomas and two neurofibromas. The results confirmed IMFT positivity for smooth muscle actin, desmin and cytokeratin in 78-89% cases, resulting in potential confusion with sarcomatoid carcinoma or leiomyosarcoma. In contrast, cytoplasmic anaplastic lymphoma kinase (ALK 1) staining was present in eight IMFT (89%), but was not seen in any other lesion examined. The ALK 1 staining was confirmed by fluorescence in situ hybridisation, with translocation of the ALK gene present in 15-60% tumour cells in four of six IMFT examined, but not in four cases of sarcomatoid carcinoma or three of leiomyosarcoma. In conclusion, ALK 1 staining may be of value in the distinction of vesical IMFT from morphologically similar entities, and often reflects ALK gene translocations in these lesions.

Is laparoscopic bladder diverticulectomy after transurethral resection of the prostate safe and effective? Comparison with open surgery.

PURPOSE: In a retrospective nonrandomized study, we compared our experience with transurethral resection of the prostate (TURP) plus sequential laparoscopic bladder diverticulectomy with a series of combined open bladder diverticulectomies with transvesical prostatectomy. PATIENTS AND METHODS: We considered 12 consecutive patients (group A) having 16 diverticula who underwent sequential TURP and transperitoneal laparoscopic bladder diverticulectomy and 13 consecutive patients (group B) having 13 diverticula who underwent open bladder diverticulectomy and transvesical prostatectomy. We evaluated the size and position of the diverticulum, adenoma volume, operative time, postoperative hemoglobin variations, analgesia requirement, complications, postoperative hospital stay, and uroflowmetry results. RESULTS: No statistically significant differences existed between the groups in adenoma volume or diverticulum size or position. However, a significantly longer operative time was recorded in group A. The endolaparoscopic approach proved to be statistically superior to open surgery regarding blood loss, postoperative analgesia requirement, and hospital stay. No intraoperative complications were recorded. In addition, no statistically significant difference was found in uroflowmetry results. CONCLUSIONS: In our experience, the endolaparoscopic approach has proved to be safe, effective, and minimally invasive and therefore superior to transvesical prostatectomy and open bladder diverticulectomy. Its only disadvantage is the longer operative time.

Effect of Withania somnifera on cyclophosphamide-induced urotoxicity.

Administration of an extract from the plant Withania somnifera (Family: Solanaceae) (20 mg/dose/animal; i.p.) for five days along with cyclophosphamide (CTX) (1.5 mmol/kg body wt. i.p.) reduced the CTX induced urotoxicity. Morphological analysis of the bladders of the CTX-treated group showed severe inflammation and dark coloration whereas CTX along with the Withania-treated group showed normal bladder morphology. The extract was found to reduce the protein level in the serum (7.92 g/l) after 4 h of CTX treatment, which was higher in the CTX alone-administered group (11.44 g/l). Blood urea N2 level which was drastically enhanced (136.78 mg/100 ml) 2 after the CTX treatment was significantly reduced (52.08 mg/100 ml) when the animals were treated with Withania extract. Similarly the glutathione (GSH) content in both bladder (1.55 micromol/mg protein) and liver (3.76 micromol/mg protein) was enhanced significantly (P<0.001) in the Withania-treated group compared with the CTX alone-treated animals (bladder 0.5 micromol/mg protein; liver 1.2 micromol/mg protein) Histopathological analysis of the bladder of CTX alone-treated group showed severe necrotic damage where as the Withania somnifera-treated group showed normal bladder architecture.

Treating the human bladder with capsaicin: is it safe?

OBJECTIVES: Although human contact with capsaicin has occurred over thousands of years, some uncertainty surrounds its status as a possible carcinogen. This is the first report of bladder biopsies from patients who have been treated with capsaicin over a 5-year period. METHODS: Between 1991 and 1996, 20 patients (9 males, 11 females; mean age 52.5 years, range 40-70 years) with intractable detrusor hyperreflexia have had repeated instillations of intravesical capsaicin (1-2 mmol/l). The number of treatments per patient varied between 1 and 17 (total = 82; average 6/patient). The surveillance programme involved repeated flexible cystoscopy and bladder biopsies before and after capsaicin. Cryostat sections were stained with haematoxylin-eosin and examined by light microscopy. RESULTS: None of the bladder biopsies have shown metaplasia, dysplasia, flat carcinoma in situ, papillary or solid invasive cancer. CONCLUSIONS: No pre-malignant of malignant change has been found in biopsies of patients who had repeated capsaicin instillations for up to 5 years. However, as the morphological effects of chemical carcinogens may not be apparent for 10 years, further surveillance is being continued.

Short-term effect of pudendal nerve electrical stimulation on detrusor hyperreflexia in spinal cord injury patients: importance of current strength.

Twenty patients with chronic suprasacral spinal cord injury presenting with detrusor hyperreflexia were examined. In a preliminary study in ten patients we investigated the reproducibility of bladder capacity through the repetition of three cystometries. The effect of electrical stimulation (ES) on detrusor hyperreflexia was then investigated in ten patients during three consecutive cystometries, the first one without ES (baseline) and the other two with continuous ES of the dorsal penile or clitoris nerve via surface electrodes. Parameters of stimulation were 5 Hz frequency, 0.50 msec pulse duration, and stimulation strength of 1 and 2 times the bulbocavernosus reflex threshold. No significant differences in bladder capacity were found between the three consecutive cystometries without ES (respectively 97.0 ml, 101.5 ml and 105.6 ml). A current at the bulbocavernosus threshold (mean 24.4 mA) failed to induce a significant increase in bladder capacity compared to baseline (173.0 ml vs 155.5 ml, P = 0.17) whereas a current of twice the bulbocavernosus threshold (mean 48.9 mA) was highly significant (318.5 ml vs 155.5 ml, P < 0.007). ES of twice the threshold resulted in perineal contraction in all of the patients, the threshold ES never did. Our results emphasise the decisive roles of perineal contraction and of current strength for achieving short-term bladder inhibition in spinal cord injury patients. The carry-over effect may also be dependent on the current strength. If so, maximal pudendal ES could represent an alternative procedure in the treatment of detrusor hyperreflexia in these patients.

Calcification of the urinary bladder in the wild cotton rat (Sigmodon hispidus).

Calcification of the urinary bladder epithelium was observed in 19 of 30 and 18 of 30 wild cotton rats from control and petrochemical-contaminated sites, respectively. The rats in the two sites did not differ significantly in respect of serum calcium and phosphorus concentrations. The calcification was considered to be dystrophic in nature. An unidentified factor common to both control and petrochemical-contaminated sites was considered to be responsible for this syndrome.

[Malacoplakia of the large intestine, bladder and retroperitoneum: a case report]. / Malacoplasia do intestino grosso, bexiga e retroperitônio: relato de um caso.

The authors present a case of malakoplakia, involving colon, rectum, bladder and retroperitoneum. This rare pathology, generally associated to Escherichia coli infections, result in a granulomatous disease, that can involve one or more organs. Nowadays, it is believed that the illness is due to a failure in the bactericide activity of the macrophage. This case, the first reported in our country, was treated clinically with ascorbic acid and trimethoprim-sulfamethoxazole, and is also unique in the world literature.

Directed intravascular precipitation of bisantrene for pelvic malignant lesions: preclinical studies.

Bisantrene, a clinically active anticancer drug with limited solubility at physiologic pH, was delivered by selective injection into the internal iliac artery of male calves. The percutaneous transfemoral angiographic techniques used in the calves were identical to those used in adult human patients. Directed intravascular precipitation of bisantrene at the maximal tolerable clinical dose for intravenous administration (260 mg/m2) caused severe tissue damage in 5 of 10 animals that received these intra-arterial injections. (One calf in this study group died of unknown causes 10 days after the drug infusion). A reduced intra-arterial dose (50 mg/m2) was used in seven calves, and no local tissue damage was evident on gross or microscopic examination. Nevertheless, resultant concentrations of bisantrene deposited in the ipsilateral bladder wall were 10- to 100-fold those concentrations found after intravenous administration of a dose 5 times higher. These animal toxicology and pharmacology data support initiation of a phase I clinical trial of directed intravascular precipitation of bisantrene in humans. This clinical trial will be developed for patients with advanced refractory cancers of the anatomic true pelvis, such as those originating in the urinary bladder, prostate, rectum, and uterine cervix.

Prevention of cyclophosphamide cystitis with 2-mercaptoethane sodium sulfonate: a histologic study.

The ability of 2-mercaptoethane sodium sulfonate to prevent histologic damage to the bladder from cyclophosphamide was studied. Male rats receiving 2-mercaptoethane sodium sulfonate in conjunction with cyclophosphamide had a statistically significant decrease in ulceration, inflammation and edema of the bladder compared to those treated with cyclophosphamide alone. Most bladders of animals given prophylactic 2-mercaptoethane sodium sulfonate with a dose of cyclophosphamide were histologically indistinguishable from controls receiving neither drug. The relevance of these findings to the short and long-term effects of cyclophosphamide on the urothelium is discussed.