[Male Refractory Urethral Diverticular Abscess Requiring Transurethral Fenestration : A Case Report].

An 85 year-old man was referred to our hospital because of a relapse of abscess after open surgical drainage of the right scrotum. Computed tomography (CT) showed fluid accumulation in the right scrotum and around the membranous urethra. The abscess was controlled by an open surgical drainage of the right scrotum, CT guided percutaneous drainage of the periurethral abscess and administration of antibiotics. However, the scrotal abscess recurred after 4 weeks. CT showed an enlarged abscess, and retrograde urethrography showed an urethral diverticulum extending into the scrotum associated with a scrotal abscess. Endoscopic urethral diverticulum unroofing and cautery were performed. The urinary catheter was removed 2 days after the operation. The abscess has been resolved without recurrence.

Two cases of pyelonephritis with bacteremia by Staphylococcus epidermidis in male patients with nephrolithiasis: Case reports and a literature review.

BACKGROUND: Staphylococcus epidermidis is a common cause of health care-associated bacteremia, especially in patients with an indwelling medical device. However, S. epidermidis is an uncommon causative organism in catheter-associated urinary tract infection, and rare pyelonephritis without any indwelling urinary device. To our knowledge, there are few cases reported of bacteremia secondary to urinary tract infection. We report two cases of pyelonephritis with bacteremia by S. epidermidis in male patients with unilateral nephrolithiasis and review prior case reports. CASE PRESENTATION: Case 1: 74-year-old man with a history of diabetes and overactive bladder had fever and pyuria with a right nephrolithiasis on abdominal CT scan. Case 2: 79-year-old man with a history of diabetes and post-myocardial infarction status had fever with a left nephrolithiasis on abdominal CT scan. In both cases, both the urine culture collected at ureteral stenting and blood culture were positive for S. epidermidis. We initiated intravenous antibiotics in these patients in addition to ureteral stenting. CONCLUSIONS: S. epidermidis is acknowledged as an uncommon pathogen that can cause bacteremia secondary to pyelonephritis without an indwelling urinary device. Clinicians should consider the possibility of pyelonephritis due to S. epidermidis if the pathogen is identified in blood and urine in patients with nephrolithiasis.

[A Case of Penile Pyoderma Gangrenosum Treated by Urethrocutaneostomy without Penectomy].

We herein report a case of penile pyoderma gangrenosum that was successfully treated with prednisolone and by urethrocutaneostomy without penectomy. A man in his 50s visite dour department because of painful urination. Pyuria and redness of the external urethral meatus were present. Treatment for urethritis with antibiotics did not improve his symptoms, and a painful ulcer and fistula formation between the glans and urethra subsequently developed. Microbiological cultures revealed no growth, and punch biopsy showed only nonspecific inflammation, leading to a diagnosis of penile pyoderma gangrenosum. We initiated prednisolone (PSL) at 40 mg once daily following placement of an indwelling suprapubic cystostomy tube for dysuria. However, the treatment was ineffective. Therefore, the dosage of PSL was increased to 65 mg once daily. The ulcer disappeared， but urethral stricture remained. Six hundred days after PSL treatment, we performed urethrocutaneostomy. The patient became free of the cystostomy and was able to urinate spontaneously. In recent years, there has been an increasing number of reports of penile preservation in the treatment of penile pyoderma gangrenosum, but knowledge regarding which patients require urethral surgery is lacking. Urologists should keep in mind increased susceptibility to infection, pathergy and possible recurrence, when considering urethral surgery for penile pyoderma gangrenosum.

Stretch- and carbachol-induced ATP release from bladder wall preparations of young and aged mice.

AIMS: Bladder wall stretch increases tissue tension and releases adenosine 5'-triphosphate (ATP) as part of a transduction process to sense bladder filling. Aging is associated with bladder fibrosis to produce a stiffer bladder wall: this may augment ATP release and contribute to age-dependent urgency. Muscarinic agonists also release ATP and present a potential target for antimuscarinic agents, but its age-dependency is unknown. This study aimed, in young and old mice, to: (a) quantify the relationship between bladder wall stiffness and stretch-dependent ATP release and; (b) characterize muscarinic agonist-dependent release. METHODS: ATP release from young (9-12 weeks) and aged (24 months) mouse bladder wall was measured in vitro, with a luciferin-luciferase assay, after stretch or carbachol exposure. Bladder wall stiffness, measured simultaneously during stretch, was compared to histological proportions of connective tissue and detrusor muscle. RESULTS: With young mice, stretch-activated ATP release required an intact mucosa and was positively associated with wall stiffness. ATP release by carbachol was about four-fold greater compared to stretch. With aged mice: ATP release varied a hundred-fold and no association with stiffness; carbachol release diminished; connective tissue and mucosa thickness increased. CONCLUSIONS: With young mice, stretch, or muscarinic agonists potently induce bladder wall ATP release. Stretch-dependent release is proportional to bladder wall stiffness, independent of the extent of stretch. With aged mice dependence of stretch-activated ATP release with stiffness was lost. The huge variability of release suggests that aged mice do not form a homogenous cohort and may underlie the heterogeneity in bladder filling sensations.

Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1 in normal and diseased bladder detrusor muscles: a clinico-pathological study.

BACKGROUND: To investigate the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant that functions via PTH1R. We hypothesized that suppression of this axis could be involved in the pathogenesis of bladder disease. METHODS: PTH1R expression in clinical samples was examined by immunohistochemistry. Normal kidney tissue from a patient with renal cancer and bladder specimens from patients undergoing ureteral reimplantation for vesicoureteral reflux or partial cystectomy for urachal cyst were examined as normal control organs. These were compared with 13 diseased bladder specimens from patients undergoing bladder augmentation. The augmentation patients ranged from 8 to 31 years old (median 15 years), including 9 males and 4 females. Seven patients had spinal disorders, 3 had posterior urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome). RESULTS: Renal tubules, detrusor muscle and blood vessels in normal control bladders stained positive for PTH1R. According to preoperative urodynamic studies of augmentation patients, the median percent bladder capacity compared with the age-standard was 43.6% (range 1.5-86.6%), median intravesical pressure at maximal capacity was 30 cmH2O (range 10-107 cmH2O), and median compliance was 3.93 ml/cmH2O (range 0.05-30.3 ml/cmH2O). Detrusor overactivity was observed in five cases (38.5%). All augmented bladders showed negative stainings in PTH1R expression in the detrusor tissue, but positive staining of blood vessels in majority of the cases. CONCLUSIONS: Downregulation of PTH1R may be involved in the pathogenesis of human end-stage bladder disease requiring augmentation.

Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development.

Overactive bladder (OAB) is a pervasive clinical problem involving alterations in both neurogenic and myogenic activity. While there has been some progress in understanding neurogenic inputs to OAB, the mechanisms controlling myogenic bladder activity are unclear. We report the involvement of myocardin (MYOCD) and microRNA-1 (miR-1) in the regulation of connexin 43 (GJA1), a major gap junction in bladder smooth muscle, and the collective role of these molecules during post-natal bladder development. Wild-type (WT) mouse bladders showed normal development from early post-natal to adult including increases in bladder capacity and maintenance of normal sensitivity to cholinergic agents concurrent with down-regulation of MYOCD and several smooth muscle cell (SMC) contractile genes. Myocardin heterozygous-knockout mice exhibited reduced expression of Myocd mRNA and several SMC contractile genes concurrent with bladder SMC hypersensitivity that was mediated by gap junctions. In both cultured rat bladder SMC and in vivo bladders, MYOCD down-regulated GJA1 expression through miR-1 up-regulation. Interestingly, adult myocardin heterozygous-knockout mice showed normal increases in bladder and body weight but lower bladder capacity compared to WT mice. These results suggest that MYOCD down-regulates GJA1 expression via miR-1 up-regulation, thereby contributing to maintenance of normal sensitivity and development of bladder capacity.

[A cyst arising from tunica vaginalis testis : report of a case].

A 38-year-old man presented with left intrascrotal painless mass. Ultrasound and magnetic resonance imaging (MRI) examinations demonstrated a cystic lesion at the upper side of left testis without enhancement. This mass gradually enlarged in size, and left high orchiectomy was planned. Because intraoperative finding showed a cyst arising from tunica vaginalis testis, excision of the cyst was performed. Histopathological examination showed a cyst with a fibrous wall lined with cuboidal endothelial cells without malignancy. To our knowledge, this is the 15th reported case of a benign cystic lesion in tunica vaginalis testis in Japan. The age distribution of patients showed two peaks ; one from 5 to 8 years old and the other from 30 to 69 years old. Most of the pediatric patients showed acute scrotal swelling with pain. On the other hand, most adult patients demonstrated painless scrotal swelling with slow growth. Operative investigation should be performed in cases with suspicion of malignancy.

[false-positive results of human chorionic gonadotropin ß measurement after high orchiectomy for stage i seminoma: report of a case].

A 21-year-old male presented at our hospital with a complaint of left scrotal swelling. The serum human chorionic gonadotropin-ß (hCG-ß) level was 1.3 ng/ml. A left high orchitectomy was performed, and a histological study demonstrated seminoma. Computerized tomography showed no evidence of metastasis. Adjuvant radiation therapy with 25 Gy was performed for stage I seminoma. Although complete clinical remission was achieved,the hCG-ß level remained slightly positive (0.3-0.5 ng/ml). The urine hCG-ß-core fragment was determined to be within normal limits. This confirmed that the result of serum hCG-ß measurement was false-positive in our case. The patient received no additional treatment, and is free from recurrence 3 years and 1 month after surgery. In the testicular germ cell tumors,the measurement of urine hCG-ß-core fragment is useful for differential diagnosis in cases of low level-positive serum hCG-ß without clinical evidence of disease.

[Clinical study of tubeless cutaneous ureterostomy].

We constructed Toyoda cutaneous ureterostomy with fixation between the anterior and posterior rectus sheath by four interrupted sutures to maintain the stability of the abdominal wall tunnel for the ureters. After the operation, the stent catheters were placed in the renal pelvis through the stoma, and exchanged every 4 weeks. The stent catheters were removed 3 months after the operation, because the stomal conditions were unstable and obstructive in the early phase after the operation. Fifteen patients (27 renal units) with at least 6 months of follow-up were enrolled in this study. The follow-up period was 6 to 33 months (average 14.0 +/- 7.9). Radical cystectomy was performed for bladder cancer in these patients. There were 12 men and 3 women with an average age of 73.3 +/- 7.2 years. At the operation, the ureters were intact in all 27 renal units. Six months after operation, 26 (96.3%) of 27 renal units achieved a tubeless condition, and 25 renal units (92.6%) had no hydronephrosis. Acute pyelonephritis had developed 2 (13.3%) of the 15 patients both within 3 months after the operation and after this period. In conclusion, our operative modification of cutaneous ureterostomy achieved a high catheter-free rate.

Influence of sildenafil on the purinergic components of nerve-mediated and urothelial ATP release from the bladder of normal and spinal cord injured mice.

BACKGROUND AND PURPOSE: PDE inhibitors such as sildenafil alleviate lower urinary tract symptoms; however, a complete understanding of their action on the bladder remains unclear. We are investigating the effects of sildenafil, on post and preganglionic nerve-mediated contractions of the mouse bladder, and neuronal and urothelial ATP release. EXPERIMENTAL APPROACH: Bladders were used from young (12 weeks), aged (24 months), and spinal cord transected (SCT), mice, for in vitro contractility experiments. An arterially perfused in situ whole mouse model was used to record bladder pressure. Nerve-mediated contractions were generated by electrical field stimulation (EFS) of postganglionic nerve terminals or the pelvic nerve. ATP release during EFS in intact detrusor strips, and during stretch of isolated mucosa strips, was measured using a luciferin-luciferase assay. KEY RESULTS: Sildenafil (20 µM) inhibited nerve-mediated contractions in young mice, with an increase in f1/2 values in force-frequency relationships, demonstrating a greater effect at low frequencies. Sildenafil reduced the atropine-resistant, purinergic component of nerve-mediated contractions, and suppressed neuronal ATP release upon EFS in vitro. Sildenafil reduced the preganglionic pelvic nerve stimulated bladder pressure recordings in situ; comparable to in vitro experiments. Sildenafil reduced stretch-induced urothelial ATP release. Sildenafil also relaxed nerve-mediated contractions in aged and SCT mice. CONCLUSION AND IMPLICATIONS: Sildenafil has a greater effect on the low-frequency, purinergic-mediated contractions and suppresses neuronal ATP release. In addition, sildenafil reduces stretch-induced urothelial ATP release. These results demonstrate a novel action of sildenafil to selectively inhibit ATP release from nerve terminals innervating detrusor smooth muscle and the urothelium.

Circadian coordination of ATP release in the urothelium via connexin43 hemichannels.

Day-night changes in the storage capacity of the urinary bladder are indispensable for sound sleep. Connexin 43 (Cx43), a major gap junction protein, forms hemichannels as a pathway of ATP in other cell types, and the urinary bladder utilizes ATP as a mechanotransduction signals to modulate its capacity. Here, we demonstrate that the circadian clock of the urothelium regulates diurnal ATP release through Cx43 hemichannels. Cx43 was expressed in human and mouse urothelium, and clock genes oscillated in the mouse urothelium accompanied by daily cycles in the expression of Cx43 and extracellular ATP release into the bladder lumen. Equivalent chronological changes in Cx43 and ATP were observed in immortalized human urothelial cells, but these diurnal changes were lost in both arrhythmic Bmal1-knockout mice and in BMAL1-knockdown urothelial cells. ATP release was increased by Cx43 overexpression and was decreased in Cx43 knockdown or in the presence of a selective Cx43 hemichannel blocker, which indicated that Cx43 hemichannels are considered part of the components regulating ATP release in the urothelium. Thus, a functional circadian rhythm exists in the urothelium, and coordinates Cx43 expression and function as hemichannels that provide a direct pathway of ATP release for mechanotransduction and signalling in the urothelium.

[Rupture of renal artery aneurysm during pregnancy].

We report a case of renal artery aneurysm ruptured during pregnancy. A 32-year-old woman presented at 38th week of gestation with left flank pain. We performed a cesarean delivery for fetal distress, and found retroperitoneal hemorrhage. After delivery, she entered a pre-shock state, and abdominal computed tomography and angiography showed a left renal artery aneurysm and hemorrhage from the aneurysm. Left nephrectomy was performed, and both mother and baby were rescued. Renal artery rupture during pregnancy is a fatal event, but with quick diagnosis and adequate treatment, if possible nephron sparing surgery, most patients, including babies, can be rescued.

[A case of malignant lymphoma with bilateral adrenal involvement].

Since the adrenal gland is a common site of metastatic disease, it is sometimes difficult to find the primary lesion only by diagnostic imaging. We report a case of non-Hodgkin's lymphoma with bilateral adrenal involvement, in which percutaneous needle biopsy was useful to determine the histology.

[A multi-center prospective study for antibiotic prophylaxis to prevent perioperative infections in urologic surgery].

In order to assess the ability of our protocol for antibiotic prophylaxis to prevent perioperative infections in urologic surgery, 1,353 operations of open and laparoscopic urologic surgery conducted in 21 hospitals between September 2002 and August 2003 were subjected to analyses. We classified surgical procedures into four categories by invasiveness and contamination levels: Category A; clean less invasive surgery, Category B; clean invasive or clean-contaminated surgery, Category C; surgery with urinary tract diversion using the intestine. Prophylactic antibiotics were administrated intravenously according to our protocol, such as Category A; first or second generation cephems or penicillins on the operative day only, Category B; first and second generation cephems or penicillins for 3 days, and Category C; first, second or third generation cephems or penicillins for 4 days. The wound conditions and general conditions were evaluated in terms of the surgical site infection (SSI) as well as remote infection (RI) up to postoperative day (POD) 30. The SSI rate highest (23.3%) for surgery with intestinal urinary diversion, followed by 10.0% for surgery for lower urinary tract, 8.9% for nephroureterctomy, and 6.0% for radical prostatectomy. The SSI rates in clean surgery including open and laparoscopic nephrectomy/adrenalectomy were 0.7 and 1.4%, respectively. In SSIs, gram-positive cocci such as methicillin-resistant Staphylococcus aureus (58.8%) or Enterobacter faecalis (26.5%) were the most common pathogen. Similarly, the RI rate was the highest (35.2%) for surgery using intestinal urinary diversion, followed by 16.7% for surgery for lower urinary tract, 11.4% for nephroureterctomy, and 7.6% for radical prostatectomy, while RI rates for clean surgery were less than 5%. RIs most frequently reported were urinary tract infections (2.6%) where Pseudomonas aeruginosa (20.3%) and Enterobacter faecalis (15.3%) were the major causative microorganisms. Parameters such as age, obesity, nutritional status (low proteinemia), diabetes mellitus, lung disease, duration of operation, and blood loss volume were recognized as risk factors for SSI or RI in several operative procedures. Postoperative body temperatures, peripheral white blood counts, C reactive protein (CRP) levels in POD 3 were much higher than those in POD 2 in cases suffering from perioperative infections, especially suggesting that CRP could be a predictable marker for perioperative infections.

Altered detrusor gap junction communications induce storage symptoms in bladder inflammation: a mouse cyclophosphamide-induced model of cystitis.

Lower urinary tract symptoms (LUTS) include storage, voiding and post-micturition symptoms, featuring many urological diseases. Storage symptoms are the most frequent among these and associated with overactive bladder and non-bacterial bladder inflammation such as interstitial cystitis/bladder pain syndrome (IC/BPS). Gap junction, a key regulator of hyperactive conditions in the bladder, has been reported to be involved in pathological bladder inflammation. Here we report involvement of gap junction in the etiology of storage symptoms in bladder inflammation. In this study, cyclophosphamide-induced cystitis was adapted as a model of bladder inflammation. Cyclophosphamide-treated mice showed typical storage symptoms including increased urinary frequency and reduced bladder capacity, with concurrent up-regulation of connexin 43 (GJA1), one of the major gap junction proteins in the bladder. In isometric tension study, bladder smooth muscle strips taken from the treated mice showed more pronounced spontaneous contraction than controls, which was attenuated by carbenoxolone, a gap junction inhibitor. In voiding behavior studies, the storage symptoms in the treated mice characterized by frequent voiding were alleviated by 18α-glycyrrhetinic acid, another gap junction inhibitor. These results demonstrate that cyclophosphamide-induced mouse model of cystitis shows clinical storage symptoms related with bladder inflammation and that gap junction in the bladder may be a key molecule of these storage symptoms. Therefore, gap junction in the bladder might be an alternative therapeutic target for storage symptoms in bladder inflammation.

PTHrP is endogenous relaxant for spontaneous smooth muscle contraction in urinary bladder of female rat.

Acute bladder distension causes various morphologic and functional changes, in part through altered gene expression. We aimed to investigate the physiologic role of PTHrP, which is up-regulated in an acute bladder distension model in female rats. In the control Empty group, bladders were kept empty for 6 hours, and in the Distension group, bladders were kept distended for 3 hours after an artificial storing-voiding cycle for 3 hours. In the Distention group bladder, up-regulation of transcripts was noted for 3 genes reported to be up-regulated by stretch in the cultured bladder smooth muscle cells in vitro. Further transcriptome analysis by microarray identified PTHrP as the 22nd highest gene up-regulated in Distension group bladder, among more than 27,000 genes. Localization of PTHrP and its functional receptor, PTH/PTHrP receptor 1 (PTH1R), were analyzed in the untreated rat bladders and cultured bladder cells using real-time RT-PCR and immunoblotting, which revealed that PTH1R and PTHrP were more predominantly expressed in smooth muscle than in urothelium. Exogenous PTHrP peptide (1-34) increased intracellular cAMP level in cultured bladder smooth muscle cells. In organ bath study using bladder strips, the PTHrP peptide caused a marked reduction in the amplitude of spontaneous contraction but caused only modest suppression for carbachol-induced contraction. In in vivo functional study by cystometrogram, the PTHrP peptide decreased voiding pressure and increased bladder compliance. Thus, PTHrP is a potent endogenous relaxant of bladder contraction, and autocrine or paracrine mechanism of the PTHrP-PTH1R axis is a physiologically relevant pathway functioning in the bladder.

BALB/c-Fcgr2bPdcd1 mouse expressing anti-urothelial antibody is a novel model of autoimmune cystitis.

We report the impact of anti-urothelial autoantibody (AUAb) on urinary bladder phenotype in BALB/c mice deficient of the FcγRIIb and PD-1. AUAb was present in serum samples from approximately half of the double-knockout (DKO) mice, as detected by immunofluorescence and immunoblots for urothelial proteins including uroplakin IIIa. The AUAb-positive DKO mice showed degeneration of urothelial plaque and umbrella cells, along with infiltration of inflammatory cells in the suburothelial layer. TNFα and IL-1ß were upregulated in the bladder and the urine of AUAb-positive DKO mice. Voiding behavior of mice was analyzed by the Voided Stain on Paper method. 10-week-old and older AUAb-positive DKO mice voided significantly less urine per void than did wild type (WT) mice. Furthermore, administration of the AUAb-containing serum to WT mice significantly reduced their urine volume per void. In summary, this report presents a novel comprehensive mouse model of autoimmune cystitis.

Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm.

Nocturnal enuresis in children and nocturia in the elderly are two highly prevalent clinical conditions characterized by a mismatch between urine production rate in the kidneys and storage in the urinary bladder during the sleep phase. Here we demonstrate, using a novel method for automated recording of mouse micturition, that connexin43, a bladder gap junction protein, is a negative regulator of functional bladder capacity. Bladder connexin43 levels and functional capacity show circadian oscillations in wild-type mice, but such rhythms are completely lost in Cry-null mice having a dysfunctional biological clock. Bladder muscle cells have an internal clock, and show oscillations of connexin43 and gap junction function. A clock regulator, Rev-erbα, upregulates connexin43 transcription as a cofactor of Sp1, using Sp1 cis-elements of the promoter. Therefore, circadian oscillation of connexin43 is associated with the biological clock and contributes to diurnal changes in bladder capacity, which avoids disturbance of sleep by micturition.

Evaluation of hydronephrosis with tubeless cutaneous ureterostomy using Tc-99m MAG3 diuretic renography.

PURPOSE: To assess hydronephrosis of tubeless cutaneous ureterostomy using Tc-99m mercaptoacetyltriglycine (MAG3) diuretic renogram. MATERIALS AND METHODS: Cutaneous ureterostomy with a unilateral stomal creation was performed in 15 patients (27 renal units) with a minimum follow-up period of 6 months. Stomal obstruction was evaluated with Tc-99m MAG3 diuretic renography 3 months after the surgery. The data analyses were performed with half-times to tracer clearance (T1/2) after furosemide (0.5 mg/kg) administration. RESULTS: T1/2 means were 7.27 +/- 7.11, 5.69 +/- 4.63, and 8.96 +/- 8.37 minutes for total, ipsilateral, and contralateral kidneys, respectively, in side relationships between ureter and stoma. There were no statistical differences among the groups. Six months after the surgery, of 26 renal units (96.3%) that had achieved a tubeless condition, and 25 renal units (92.6%) had no hydronephrosis. T1/2 was within 20 minutes in these 25 renal units, and of 25 renal units 23 (92%) revealed less than 15 minutes in T1/2, suggesting that the upper limit of T1/2 for nonobstructed systems after construction of a cutaneous ureterostomy might be 15 minutes. Mild hydronephrosis without the need for intervention was present in 1 renal unit (T1/2, 31.70 minutes). Catheterization was performed in one renal unit (T1/2, 21.04 minutes) due to acute pyelonephritis and persistence of grade 2 hydronephrosis 5 months after the surgery. Only these 2 renal units showed more than 20 minutes in T1/2, resulting in an obstructive pattern on diuretic renography. CONCLUSION: Tc-99m MAG3 diuretic renography with T1/2 assessment is useful to evaluate stomal stenosis in tubeless cutaneous ureterostomy.