Translocation of NF-κB and expression of cyclooxygenase-2 are enhanced by ketamine-induced ulcerative cystitis in rat bladder.

The number of ketamine abusers has increased significantly recently. Ketamine abusers exhibit urinary frequency, urgency, and at times urinary incontinence. Our aim was to investigate the role of transcription factor NF-κB and cyclooxygenase (COX)-2 in ketamine-induced cystitis. Sprague-Dawley rats were distributed into three groups, which received saline or treatment with ketamine or ketamine combined with a Cox-2 inhibitor (parecoxib). In addition, the toxic effect of ketamine and its metabolites were examined by primary urothelial cell culture. The ketamine-treated group displayed bladder hyperactivity and decreased bladder capacity. Treatment with ketamine + COX-2 inhibitor prevented these bladder dysfunctions. These bladder dysfunctions were accompanied by increases in the expression of NF-κB and COX-2 at the protein and mRNA levels. Ketamine treatment also enhanced bladder interstitial fibrosis, whereas ketamine + Cox-2 inhibitor decreased the intensity of fibrosis. Treatment of primary urothelial cells in vitro with ketamine or urine obtained from ketamine-treated rats stimulated the expression of NF-κB p65 and COX-2. Ketamine also initiated NF-κB translocation from cell cytoplasm to nucleus. Treatment with NF-κB inhibitor suppressed Cox-2 mRNA expression. Promoter-deletion analysis revealed that NF-κB was a necessary transcription factor for COX-2 gene (Ptgs2) activation. These results demonstrate that the regulation of COX-2 via the NF-κB pathway is involved in the inflammatory signaling of ketamine-induced cystitis in rat urinary bladder.

Ketamine-induced ulcerative cystitis and bladder apoptosis involve oxidative stress mediated by mitochondria and the endoplasmic reticulum.

Ketamine abusers develop severe lower urinary tract symptoms. The major aims of the present study were to elucidate ketamine-induced ulcerative cystitis and bladder apoptosis in association with oxidative stress mediated by mitochondria and the endoplasmic reticulum (ER). Sprague-Dawley rats were distributed into three different groups, which received normal saline or ketamine for a period of 14 or 28 days, respectively. Double-labeled immunofluorescence experiments were performed to investigate tight junction proteins for urothelial barrier functions. A TUNEL assay was performed to evaluate the distribution of apoptotic cells. Western blot analysis was carried out to examine the expressions of urothelial tight junction proteins, ER stress markers, and apoptosis-associated proteins. Antioxidant enzymes, including SOD and catalase, were investigated by real-time PCR and immunofluorescence experiments. Ketamine-treated rats were found to display bladder hyperactivity. This bladder dysfunction was accompanied by disruptions of epithelial cadherin- and tight junction-associated proteins as well as increases in the expressions of apoptosis-associated proteins, which displayed features of mitochondria-dependent apoptotic signals and ER stress markers. Meanwhile, expressions of mitochondria respiratory subunit enzymes were significantly increased in ketamine-treated bladders. Conversely, mRNA expressions of the antioxidant enzymes Mn-SOD (SOD2), Cu/Zn-SOD (SOD1), and catalase were decreased after 28 days of ketamine treatment. These results demonstrate that ketamine enhanced the generation of oxidative stress mediated by mitochondria- and ER-dependent pathways and consequently contributed to bladder apoptosis and urothelial lining defects. Such oxidative stress-enhanced bladder cell apoptosis and urothelial barrier defects are potential factors that may play a crucial role in bladder overactivity and ulceration.

Dual involvements of cyclooxygenase and nitric oxide synthase expressions in ketamine-induced ulcerative cystitis in rat bladder.

AIMS: The aims of the present study were to investigate voiding patterns, tissue constituents and the expressions of cyclooxygenase-2 (COX-2) and nitric oxide synthase (NOS) involved in ketamine-induced ulcerative cystitis in rat urinary bladder. METHODS: Thirty Sprague-Dawley rats were distributed into three groups which received saline or ketamine (25 mg/kg/day) for a period of 14 and 28 days. In each group, cystometry was performed weekly and the concentration of ketamine and its metabolites (norketamine) was assayed. Paraffin-embedded sections were stained with Masson's trichrome stain, and ketamine-induced morphological changes were examined. Western blot analyses were carried out to examine the expressions of COX-2 and different NOS isoforms in bladder tissues. Immunofluorescence study was done to evaluate the expressions of COX-2 and macrophage infiltration (stained with ED-1 macrophage cell surface antigen) within the bladder. RESULTS: Ketamine treatment resulted in bladder hyperactivity and the non-voiding contractions were significantly increased. The urine concentrations of ketamine and norketamine were much higher in ketamine-treated group. Moreover, ulcerated urothelium and mononuclear cell infiltration were noted in ketamine-treated group. These alterations in urodynamic functions and tissue constituents were accompanied by increases in the expression of COX-2. Two NOS isoforms (iNOS and eNOS) were also overexpressed, but no significant change was observed for nNOS. COX-2 positive stained cells were significantly increased. Meanwhile, increased amounts of ED-1 positive stained macrophages were present and most of COX-2 expressed cells were co-stained with ED-1 in the early stage of ketamine treatment. CONCLUSIONS: Ketamine treatment affected bladder tissues by enhancing interstitial fibrosis and accelerating macrophages infiltration. Ketamine also initiated the up-regulations of COX-2 and iNOS and eNOS expressions. These up-regulated enzymes might play an important role in contributing to ketamine-induced alterations in micturition patterns and ulcerative cystitis.

Pituitary apoplexy induced by Gonadotropin-releasing hormone agonists for treating prostate cancer-report of first Asian case.

We present the first Asian case of a 77-year-old man who developed pituitary apoplexy (PA) soon after gonadotropin-releasing hormone agonist (GnRHa) (leuprorelin) injection to treat prostate cancer. Headache, ophthalmoplegia, visual field deficit, nausea, and vomiting are the typical characteristics of pituitary apoplexy. Though the occurrence rate is rare, the consequence of this condition can vary from mild symptoms such as headache to life-threatening scenarios like conscious change. Magnetic resonance imaging is the best imaging modality to detect PA and sublabial trans-sphenoid pituitary tumor removal can resolve most of PA symptoms and is so far the best solution in consensus. We also review 11 previous reported cases receiving GnRHa for androgen deprivation therapy of prostate cancer, and hope to alert clinicians to use GnRHa with caution.

Primary small cell carcinoma of kidney after renal transplantation: a case report and literature review.

Extrapulmonary small cell carcinoma (EPSCC) is a rare neoplasm comprising 2.5% to 5% of small cell carcinomas (SCCs). Bladder SCC is the most common site of genitourinary tract. Primary renal SCC is extremely rare. We report a case of primary SCC of the kidney which is rarely reported in the urinary tract and presents an aggressive clinical picture. A 59-year-old female visited a urologic clinic with complaint of persistent left flank soreness 10 years after undergoing renal transplantation. Abdominal computed tomography showed a left renal pelvis tumor. After the patient received left nephroureterectomy with bladder cuff resection, her pathology results showed SCC. After surgery, she received adjuvant systemic chemotherapy, and her recovery has been uneventful as of 8 months. Primary renal SCC presents with an advanced tumor stage and a short median survival period, therefore early intervention and close follow-up are recommended.

Conservative Bladder Management and Medical Treatment in Chronic Spinal Cord Injury Patients.

To review the available data on non-surgical management for neurogenic lower urinary tract dysfunction (NLUTD) in patients with chronic spinal cord injury (SCI) and provide the most updated knowledge for readers. We categorized the bladder management approaches into storage and voiding dysfunction separately; both are minimally invasive, safe, and efficacious procedures. The main goals for NLUTD management are to achieve urinary continence; improve quality of life; prevent urinary tract infections and, last but not least, preserve upper urinary tract function. Annual renal sonography workups and regular video urodynamics examinations are crucial for early detection and further urological management. Despite the extensive data on NLUTD, there are still relatively few novel publications and there is a lack of high-quality evidence. There is a paucity of new minimally invasive and prolonged efficacy treatments for NLUTD, and a partnership between urologists, nephrologists and physiatrists is required to promote and ensure the health of SCI patients in the future.

Sexual dysfunction in women with ketamine cystitis: a case-control study.

OBJECTIVE: • To conduct a case-control study evaluating clinical symptom severity and sexual dysfunction in women with ketamine cystitis (KC). PATIENTS AND METHODS: • In total, 29 patients with KC and 27 controls completed the symptoms survey. • Participants completed a visual pelvic pain analogue scale, an O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index questionnaire, a Female Sexual Function Index, and a short form of the Chinese Health Questionnaire-12. RESULTS: • Both the Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index scores were significantly higher in patients with KC compared to controls (P < 0.001). • The prevalence of sexual dysfunction was high in patients with KC. • There was a difference in total adjusted Female Sexual Function Index scores between the patients with KC and controls: mean (sd) total Female Sexual Function Index score 17.65 (6.15) for KC cases vs 25.87 (4.16) for controls (P < 0.001). • Except for the sexual desire domain of female sexual dysfunction, patients with KC scored lower on all domains compared to controls. • There was no significant difference between patients with KC and controls with respect to mental health as evaluated by the Chinese Health Questionnaire-12. CONCLUSIONS: • Sexual dysfunction and KC symptoms severely impacted on quality of life. • Mental health had no significant difference between patients with KC and controls.

Comparison of clinical outcome and urodynamic findings using "Perigee and/or Apogee" versus "Prolift anterior and/or posterior" system devices for the treatment of pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: This study aims to compare clinical outcome using the Perigee/Apogee® vs. Prolift® devices for the treatment of pelvic organ prolapse (POP). METHODS: One hundred and eight women with POP stages II to IV were scheduled for either Perigee/Apogee® (Perigee group; n = 60) or Prolift® device (Prolift group; n = 48). Preoperative and postoperative assessments included pelvic examination, urodynamic study, and a personal interview about urinary and sexual symptoms. RESULTS: Despite different follow-up period (20 months for the Perigee group vs. 12 months for Prolift group; P < 0.01), the success rates for two groups were comparable (P > 0.05). Postoperative points Aa and Ba of Prolift group were significantly higher than the other group (P < 0.01). The prevalences of detrusor overactivity and urinary symptoms decreased significantly postoperatively in both groups (P < 0.05). Comparisons of all operative complications revealed no significant differences between the two groups (P > 0.05). CONCLUSIONS: Perigee/Apogee® and Prolift® devices for POP repair have comparable success rates, mesh-related morbidities, and similar impacts on functional outcome.

Advanced penile verrucous carcinoma treated with intra-aortic infusion chemotherapy.

PURPOSE: Traditional treatment for advanced penile verrucous carcinoma is penectomy. This mostly leads to remarkable psychosexual problems and greatly affects quality of life, especially in young patients. To preserve the penis we used intra-aortic infusion chemotherapy for advanced verrucous carcinoma. MATERIALS AND METHODS: From 1991 to 2009 we treated 6 men with penile verrucous carcinoma with continuous intra-aortic infusion of 50 mg methotrexate every 24 hours (average 550 mg, range 400 to 800). Citrovorum factor (6 mg) was given intramuscularly every 6 hours during methotrexate infusion. After continuous methotrexate infusion no further anticancer drug was given to complete responders. Partial responders subsequently received long-term, intermittent, intra-aortic infusion of 50 mg methotrexate or 2 mg mitomycin C plus 250 mg 5-fluorouracil every 1 to 2 weeks until tumors disappeared and all wounds healed. RESULTS: After treatment 4 patients achieved a complete response and were disease-free 3 years 9 months to 17 years 10 months (median 11 years 3 months) after therapy. Two patients had a partial response. The patient with a shaft tumor subsequently underwent total penectomy due to unbearable penile pain 4 years after infusion with various drugs without an appreciable response. He has survived 12 years 5 months after initial treatment. The other patient with glans and prepuce tumors had progression with bilateral inguinal metastases despite 1 1/2 years of infusion therapy. Total penectomy was done. Histological examination of the glans mass revealed moderately differentiated squamous cell carcinoma. Patient condition progressed rapidly and he died 11 months after penectomy. CONCLUSIONS: Intra-aortic infusion chemotherapy is a simple, effective method to treat penile verrucous carcinoma with the uniqueness of preserving the anatomical structure and sexual function in complete responders. For penile verrucous carcinoma, especially in younger patients, intra-aortic infusion chemotherapy may be considered organ sparing treatment before penectomy.

Laparoscopic complete urinary tract exenteration with the specimen withdrawn transvaginally.

OBJECTIVE To describe the technique of laparoscopic complete urinary tract exenteration (LaCUTE), where specimens are withdrawn en bloc through the vagina, and to compare our results for patients had this procedure with those who had surgery by traditional open methods PATIENTS AND METHODS From February 2006 to June 2008, five patients had LaCUTE and three CUTE at our institute. The surgical procedure included bilateral nephroureterectomy, bilateral pelvic lymphadenectomy, radical cystourethrectomy, radical hysterectomy, bilateral salpingo-oophorectomy. RESULTS In the LaCUTE group the mean (range) patient age was 58 (46-73) years, the blood loss was 378 (290-490) mL, the operative duration was 492 (405-560) min and the hospital stay was 12.2 (9-17) days. All patients had negative surgical margins on pathological examination. The LaCUTE group had significantly less blood loss but longer surgery than the open group. At a mean follow-up of 14.5 and 16.0 months, respectively, there was no evidence of recurrent cancer in both groups. CONCLUSIONS With further experience and improvement in surgical techniques, LaCUTE with vaginal specimen en bloc withdrawal will become feasible for uraemic female patients with urothelial cancer.

Cocaine-related vasculitis causing scrotal gangrene.

OBJECTIVE: To describe a case of possible cocaine-related vasculitis resulting in gangrene of the scrotum and review the literature on cocaine-related vascular complications. CASE SUMMARY: A 22-year-old male presented with fever, painful swelling of the right scrotum, and a blackened ulcerated lesion on the right scrotum 3 hours after smoking crack cocaine. Blood and urine cultures and serologic tests were negative, and the D-dimer level was normal. Echocardiogram showed no evidence of vegetation and results of a chest X-ray were normal. Despite treatment for presumptive orchitis with intravenous levofloxacin 750 mg/day, the ulcerated lesion of the right scrotum progressed the next day. The patient received debridement of the necrotic tissue and pathology revealed some degenerated vessels with fibrinoid deposits and inflammatory infiltrates, suggestive of vasculitis. No further tenderness and swelling of the scrotum occurred and the patient was discharged after 10 days. When he returned for follow-up, the wound had healed completely. DISCUSSIONS: Cocaine-related vascular complications, including ischemic stroke, myocardial infarction, and peripheral occlusive disease, all of which have various possible mechanisms, are of clinical importance. Vasculitis is one of the mechanisms of vascular complications associated with cocaine use. According to the Naranjo probability scale, cocaine was the possible causative agent of the patient's vasculitis, which led to scrotum gangrene. To our knowledge, this is the first report in the literature of scrotum gangrene developing after crack cocaine was smoked. CONCLUSIONS: This case report describes a rare occurrence of gangrene of the scrotum associated with cocaine smoking, which is consistent with cocaine's potent vasoconstrictive activity. Cocaine abuse has the potential to cause clinically significant ischemic events anywhere in the body, independent of the method of administration.

Sexual and bladder dysfunction in male ketamine abusers: A large-scale questionnaire study.

PURPOSE: To evaluate the prevalence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in the illicit male ketamine abusers (KA). MATERIALS AND METHODS: The male street KAs caught by policemen and patients visiting urologic clinics were invited to answer a structured questionnaire including demographic data, illicit drug use related details (duration, frequency, dosage and abstinence status), international prostate symptoms score (IPSS), interstitial cystitis symptoms and problem index (ICSI and ICPI) and International index of erectile function (IIEF-5). Erectile dysfunction was defined as IIEF-5 ≦21. RESULTS: Finally, we included 1056 participants (993 street, 63 hospital KAs) with a mean age of 27.4 ±6.2 years. ED presented in 30.8% of all KAs. and Hospital KAs were more subject to having ED than street KAs (69.6% vs. 28.0%, p<0.01). Multi-variate analysis revealed that risk factor for male ED were age ≧30 years (OR = 1.765). Subgroup analysis on male street KAs disclosed that abstinence ≧3 months is a protective factor for ED. Lower urinary tract symptoms (ICSI+ICPI ≧12) was prevalent in KAs and multivariate analysis disclosed that significant risk factors for LUTS (ICSI+ICPI ≧12) were age ≧30 years, duration ≧24 months and co-use of other illicit drugs. CONCLUSIONS: Male ED and LUTS were frequently observed in the ketamine abusers. We suggested that street ketamine abuse should be considered in young men presented with ED and LUTS in the clinics.

Treatment of transplant ureteral stricture with Acucise endoureterotomy: case report and literature review.

We report a patient who was diagnosed with end-stage renal disease and who received renal transplantation in her right iliac fossa in 2003. After transplantation, right hydronephrosis was noted on abdominal ultrasonography and right lower ureteral stricture was diagnosed by antegrade pyelography. She received ureter internal stent insertion three times, but hydronephrosis and urinary tract infection recurred after the stent was removed. Therefore, Acucise endoureterotomy was used to treat the recurrent ureteral stricture. The patient was discharged on the second postoperative day and abdominal ultrasonography revealed no hydronephrosis during regular follow-up.

Hair as the nidus for bladder calculi formation complicating suprapubic cystostomy catheterization: a case report.

Neurogenic bladder is a familiar sequel to spinal cord injury, and bladder calculi is a common complication of neurogenic bladder. We report a case of a 25-year-old man with spinal cord injury resulting in neurogenic bladder. Permanent cystostomy was performed, and, for 4 years, the patient received periodic replacement of a cystostomy catheter. Bladder calculi were found on follow-up radiography. Cystoscopic lithotripsy was done, and it was noted that a hair was the nidus of a calculus. The hair could have been introduced into the bladder accidentally during the cystostomy catheter replacement. We suggest routine pubic hair care, even shaving, for patients suffering from neurogenic bladder with cystostomy. In addition, patients and caregivers should take care not to introduce pubic hair into the bladder while changing cystostomy catheters.

Unusual gas pattern in emphysematous cystitis: a case report.

We present a case of emphysematous cystitis in a 43-year-old female. The gas pattern was unusual because there was only gas accumulation in the urinary bladder without bladder wall thickening or intramural gas formation. The differential diagnosis included postoperative states, enterovesical fistula, and iatrogenic instrumentation. The prognosis of emphysematous cystitis is good after early diagnosis and prompt treatment with appropriate antibiotics, blood glucose control, and adequate urinary drainage. The patient was discharged on hospital day 5 with one additional week of oral antibiotic therapy. She was quite well at the time of writing and her diabetes was controlled with an oral hypoglycemic agent.

Noncontrast computed tomography factors that predict the renal stone outcome after shock wave lithotripsy.

OBJECTIVES: Extracorporeal shock wave lithotripsy (ESWL) is a popular treatment for nephrolithiasis. We took advantage of noncontrast abdominal computed tomography (NCCT) to search the possible prognostic factors including abdominal fat distribution influencing stone-free rate. METHODS: From August 2008 to August 2010, 145 patients who had renal calculus and had undergone ESWL were retrospectively reviewed. All of them received NCCT assessment before ESWL and were followed up after 1 month for stone clearance. These patients were divided into two groups: one was the stone-free group and the other was the residual-stone group. Affecting parameters included stone size, location, stone surface area, Hounsfield unit density (HU density), skin-to-stone distance (SSD), and abdominal fat area as analyzed between these two groups. RESULTS: Of 145 patients, 70 were stone-free and 75 had residual stone after ESWL treatment and 1-month follow-up. From univariate analysis, stone size, HU density, SSD, and stone surface area were significant predicting factors for ESWL success. On multivariate analysis, the important factors influencing ESWL outcomes were HU density and stone surface area (odds ratio 1.002 vs. 77.18, respectively; P<.05). Abdominal fat accumulation and distribution had no significant difference between these two groups. CONCLUSION: This study revealed that stone size, HU density, SSD, and stone surface area were associated with stone-free rate after ESWL treatment. Therefore, these factors could be used to assess the feasibility of ESWL before deciding the treatment strategy. Abdominal fat distribution had no significant impact on ESWL outcome for renal stones.

Noncontrast computed tomography can predict the outcome of shockwave lithotripsy via accurate stone measurement and abdominal fat distribution determination.

Urolithiasis is a common disease of the urinary system. Extracorporeal shockwave lithotripsy (SWL) has become one of the standard treatments for renal and ureteral stones; however, the success rates range widely and failure of stone disintegration may cause additional outlay, alternative procedures, and even complications. We used the data available from noncontrast abdominal computed tomography (NCCT) to evaluate the impact of stone parameters and abdominal fat distribution on calculus-free rates following SWL. We retrospectively reviewed 328 patients who had urinary stones and had undergone SWL from August 2012 to August 2013. All of them received pre-SWL NCCT; 1 month after SWL, radiography was arranged to evaluate the condition of the fragments. These patients were classified into stone-free group and residual stone group. Unenhanced computed tomography variables, including stone attenuation, abdominal fat area, and skin-to-stone distance (SSD) were analyzed. In all, 197 (60%) were classified as stone-free and 132 (40%) as having residual stone. The mean ages were 49.35 ± 13.22 years and 55.32 ± 13.52 years, respectively. On univariate analysis, age, stone size, stone surface area, stone attenuation, SSD, total fat area (TFA), abdominal circumference, serum creatinine, and the severity of hydronephrosis revealed statistical significance between these two groups. From multivariate logistic regression analysis, the independent parameters impacting SWL outcomes were stone size, stone attenuation, TFA, and serum creatinine. [Adjusted odds ratios and (95% confidence intervals): 9.49 (3.72-24.20), 2.25 (1.22-4.14), 2.20 (1.10-4.40), and 2.89 (1.35-6.21) respectively, all p < 0.05]. In the present study, stone size, stone attenuation, TFA and serum creatinine were four independent predictors for stone-free rates after SWL. These findings suggest that pretreatment NCCT may predict the outcomes after SWL. Consequently, we can use these predictors for selecting the optimal treatment for patients with urinary stones.

Foreign body stone in the urinary bladder: a case report.

Bladder calculi rarely form spontaneously and are usually a manifestation of an underlying pathologic condition of the lower urinary tract, including voiding dysfunction, urinary infection, obstruction, or foreign body retention. However, a ruptured Foley balloon-induced bladder stone is an unusual complication of an indwelling Foley catheter. We report a case of spinal cord injury with paraplegia and bladder stone induced by a fragment of a ruptured Foley balloon. The bladder stone and the Foley balloon fragment were successfully removed by cystoscopy. The stone was composed of calcium oxalate and calcium phosphate. We report this unusual case to raise awareness that it is important to check the integrity of the Foley catheter after removal of the tube.

Transitional cell carcinoma of the renal pelvis with extension into the inferior vena cava: a report of two cases.

Of all primary malignant renal tumors, 10% to 15% originate from the renal pelvis, and 90% to 92% of these tumors are transitional cell carcinomas. Nonetheless, renal pelvis transitional cell carcinoma extending into the inferior vena cava is very rare. We report one confirmed case and one highly suspicious case of renal pelvis transitional cell carcinoma with a tumor thrombus in the inferior vena cava. Both of our patients died within 6 months of initial diagnosis, indicating the poor prognosis and advanced stage of transitional cell carcinoma with an inferior vena cava thrombus. Transitional cell carcinoma should be considered in patients with obstruction of the renal vein and the inferior vena cava.

Laparoscopic bladder diverticulectomy for large bladder diveticulum: a case report.

Bladder diverticula are herniations of the bladder mucosa through the bladder wall musculature. Acquired bladder diverticula are the result of outlet obstruction, mostly benign prostate enlargement, infections, or urethral stricture. Traditionally, bladder diverticulum was excised by the open method. However, the laparoscopic technique has been widely used to treat many urologic diseases, including bladder diverticulum. Laparoscopic diverticulectomy can be performed transperitoneally or extraperitoneally. We report our initial experience with laparoscopic transperitoneal diverticulectomy for a large bladder diverticulum caused by bladder outlet obstruction. The patient had satisfactory micturition and was discharged on the eighth postoperative day.