[A case of extramammary Paget's disease with urethral invasion treated by construction of continent urinary diversion based on the Monti principle using the sigmoid colon].

Extramammary Paget's disease occurring in the female vulva is occasionally associated with invasive disease to urethra and bladder mucosa. For such cases, ensuring adequate surgical margin is essential. Not only adequate removal of tumor, but also urinary diversion is important for patient's quality of life. A 77- year-old woman was treated with excision of vulvar tumor, urethra, vagina, rectum and anus. The determination of excision area was decided according to the result of mapping biopsy including urethra and bladder. Then she received reconstruction of vulva using the gracilis muscle skin flap. We applied a technique of channel formation for intermittent catheterization using the retubularized sigmoid colon based on the Monti principle. The tube was implanted submucosally into the bladder to prevent the reflux of urine. Fifteen days after operation, self-intermittent catheterization was started successfully. Surgical margins were negative in urethra, skin, vagina and rectum. There are no obvious recurrence or metastasis 1 year after surgery.

Chronic urinary retention could decrease the number of suburothelial myofibroblasts in the rat bladder.

AIMS: To demonstrate changes in the number of suburothelial myofibroblasts in the rat bladder due to chronic urinary retention (CUR). METHODS: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups: a CUR group and a sham-operated group. In the CUR rats, the urethra was intubated with a polyethylene catheter, and a double 4-0 silk ligature was placed around the proximal urethra, after which the catheter was removed. After 8 weeks, the cystometric findings and immunohistochemical staining of the suburothelial myofibroblasts were compared between the groups. RESULTS: The bladder weight of the control rats was 0.20 ± 0.01 g and that of CUR rats 1.6 ± 0.4 g. The bladder capacity of the control rats was 0.5 ± 0.3 ml and that of the CUR rats 12.9 ± 3.1 ml. The number of suburothelial myofibroblasts of the control rats was 417 ± 123 and that of the CUR rats 44 ± 42. The number of suburothelial myofibroblasts in the CUR rats was significantly less than that observed in the sham-operated rats (p < 0.01). CONCLUSIONS: In this study, we demonstrated that mechanical stress over a long period on the bladder wall can decrease the number of suburothelial myofibroblasts. The reduced expression of suburothelial myofibroblasts may be related to prolongation of the micturition interval by CUR.

Assessment of lower urinary tract function in children with Down syndrome.

BACKGROUND: Despite the fact that functional lower urinary tract symptoms are common among people with Down syndrome (DS), their voiding function has not been studied precisely. Our goal was to assess the lower urinary tract functions in DS. METHODS: Fifty-five DS children aged 5-15 years old and 35 age-matched control children were evaluated by ultrasonography and uroflowmetry. RESULTS: Eleven (20%) DS children had no uresiesthesia, 21 (38%) were urinated under guidance, nine (16%) urinated fewer than three times a day, two (4%) urinated more than 10 times a day, three (5%) used diapers, and 26 (47%) had urinary incontinence. Seven (13%), 15 (27%), and 10 (18%) DS children had weak, prolonged and intermittent urination, respectively, and seven (13%) had urination with straining. In contrast, none of the control subjects had urinary problems. In the uroflowmetrical analysis, 10 (18%), 20 (37%), 11 (20%) and five (9%) DS children showed "bell-shaped," "plateau," "staccato" and "interrupted" patterns, respectively; the remaining nine (16%) could not be analyzed. In contrast, 21 (60%), one (3%), four (11%), three (9%) and two (6%) control subjects showed bell-shaped, tower-shaped, plateau, staccato and interrupted patterns, respectively; the remaining four (11%) could not be analyzed. Residual urine was demonstrated in four (7%) DS children and one (3%) control child. CONCLUSIONS: Lower urinary tract symptoms and abnormal uroflowmetry findings, which can lead to further progressive renal and urinary disorders, are common in DS children. Therefore, lower urinary tract functions should be assessed at the life-long regular medical check-ups for subjects with DS.

IgG4-related epididymo-orchitis associated with bladder cancer: possible involvement of BAFF/BAFF-R interaction in IgG4-related urogenital disease.

We describe herein a patient who presented with immunoglobulin G4-related disease (IgG4-RD) involving the testis and prostate as well as the submandibular glands. Massive infiltration of IgG4-expressing plasma cells was observed in testis and prostate tissues. Serum concentrations of B cell activating factor belonging to the tumor necrosis factor family (BAFF) were elevated in parallel with serum IgG4 concentrations, and infiltration of BAFF-receptor (BAFF-R)-expressing B cells and BAFF-expressing lymphoid cells was observed around the ectopic lymphoid foci in the affected urogenital tissues. To date, testicular involvement in a patient diagnosed with IgG4-RD had not been reported, making this the first reported case of IgG4-related epididymo-orchitis. These findings suggest that the immune mechanism underlying ectopic lymphoneogenesis in IgG4-RD may involve enhanced BAFF/BAFF-R interactions among lymphoid cells.

[A case of fistula of small intestine and ileal conduit urinary diversion improved by conservative therapy].

A 71-year-old male was admitted for bladder cancer, and we performed a radical cystectomy and urinary diversion by means of an ileal conduit. Twenty days postoperatively, we identified the presence of stool in the stoma and noted the existence of a fistula of the small intestine and ileal conduit urinary diversion. Treatment with fasting, intravenous hyperalimentation and intravenous drip administration of octreotide acetate were performed. The fistula was closed completely 47 days after the surgery. The early complications of urinary diversion by means of an ileal conduit were reported to be urinary tract infections, bowel obstruction, and delayed wound healing, but a fistula between the small intestine and ileal conduit is very rare. We herein report a case of a fistula between the small intestine and ileal conduit used for urinary diversion which thereafter healed by conservative treatment.

Changes in angiotensin II type 1 receptor expression in the rat bladder by bladder outlet obstruction.

PURPOSE: To demonstrate the change in the expression of angiotensin II type 1 receptor (AT1) in the rat bladder with partial bladder outlet obstruction (P-BOO). MATERIALS AND METHODS: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups, a P-BOO group and a control group. The rats of the P-BOO group were divided into six groups: a sham-operated control group, 1 day postoperatively, 2 days postoperatively, 4 days postoperatively, 7 days postoperatively and 14 days postoperatively. The cystometric findings and immunohistochemical staining of the detrusor muscle with the AT1 antibody were compared in each group. RESULTS: AT1 localized on the cell membrane of the detrusor smooth muscle and in cytoplasm of suburothelial myofibroblasts in the control rats. The expression of AT1 disappeared in the detrusor muscle and suburothelial myofibroblasts in P-BOO, but AT1 was highly expressed in urothelial cells 1 day after surgery. The expression of AT1 in urothelial cells gradually decreased with time after surgery. AT1 completely disappeared in urothelial cells 14 days after surgery. CONCLUSIONS: The present study demonstrated that the site of AT1 expression changes in response to the mechanical stress caused by P-BOO, and finally there was no expression of AT1 in rat bladder tissue following P-BOO. These data suggest the change in AT1 expression may play a role in bladder function.

[EARLY EXPERIENCE OF INTRAVESICAL INSTILLATION OF DIMETHYL SULFOXIDE 50% SOLUTION FOR HUNNER TYPE INTERSTITIAL CYSTITIS IN A CLINIC].

(Objectives) To analyze the early observations in intravesical instillation of dimethyl sulfoxide (DMSO) 50% solution for Hunner-type interstitial cystitis (HIC) in our clinic and discuss possible factors affecting outcomes and future tasks. (Materials and methods) Seven patients who received DMSO therapy upon HIC relapse after transurethral resection of Hunner lesions with hydrodistension were enrolled for this study. For DMSO, 50 mL of 50% intravesical solution was administered six times every two weeks. Treatment evaluation was conducted using O'Leary & Sant Interstitial Cystitis Symptom and Problem Indexes (ICSI and ICPI), numerical rating scale (NRS) for bladder pain (0-10 points), and the post-treatment variations for which the pre-treatment values of the 24-hour urinary frequency, the average voided volume, and the maximum voided volume were used. The patient satisfaction survey was conducted with a questionnaire, and cystoscopy was conducted for all cases before and after treatment. (Results) All the patients were females with an average age of 58.3 years old. According to the Society of Interstitial cystitis of Japan Severity Criteria, 5 of the 7 cases showed a moderate level. No severe side effects were observed, and all the patients achieved six times administration. Changes in the points from the pre-treatment baseline values to the post-treatment values were -6.1, -9.1, and -10.0 for Pain NRS, ICSI, and ICPI, respectively. In addition, the 24-hour urinary frequency decreased by 5.34 times, while the average voided volume and the maximum voided volume increased to 60.3 mL and 75.7 mL, respectively. Subjective symptoms of all the patients improved, and cystoscopy revealed the disappearance or remission of Hunner lesions. (Conclusions) If Hunner lesions can be diagnosed, DMSO therapy could be used effectively and safely for HIC. The therapy is also promising for use as a future initial therapy. Therefore, the accurate diagnosis of Hunner lesions will be more important in the future.

EPO-producing gastric carcinoma in a hemodialysis patient.

A case of erythrocytosis caused by gastric cancer that produced erythropoietin is described. To the authors' knowledge, no case of erythropoietin-producing gastric cancer has been reported until now. A 73-year-old man with a 4-year history of maintenance hemodialysis for diabetic nephropathy required phlebotomy. Serum erythropoietin level was 181 mU/mL (181 IU/L). Gastroscopy results showed rough mucosa with hemorrhaging caused by gastric cancer. The patient underwent distal gastrectomy, and serum erythropoietin level decreased to 27.1 mU/mL (27.1 IU/L) by postoperative day 8. Existence of erythropoietin in the tumor tissue was confirmed immunohistochemically. The presence of severe acquired cystic disease of the kidney, renal cell carcinoma, and other malignant tumors should be investigated in hemodialysis patients displaying erythrocytosis.

Natural course of voiding function in patients with human T-cell lymphotrophic virus type 1-associated myelopathy.

OBJECTIVES: Patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) frequently experience voiding dysfunction. In patients with HAM/TSP, the major symptoms are gait disturbance and voiding dysfunction. However, the detailed natural course of voiding function and the management of their urination has not previously been investigated. We examined the correlation between voiding function and clinical features and evaluated the management of urination, in the patients with HAM/TSP. PATIENTS AND METHODS: The voiding function of 47 patients (7 males, 40 females, aged 29-89 years, mean: 60.9 years) with HAM/TSP was analyzed retrospectively. All HAM/TSP patients are positive for HTLV-1. Patients were referred to a neurologist for analysis of bladder function. In the present study, we analyzed their clinical details, age at disease onset, voiding function and alterations in the management of their urination. Furthermore, we investigated the relationship between urological management and the clinical features of HAM/TSP. RESULTS: Of the 47 patients, 20 (42.5%) were able to void with or without drug therapy. Thirty-four (72.3%) experienced clean intermittent self-catheterization (CIC), with 25 of these 34 continuing CIC, 7 changing to voiding and 2 changing to management with the Foley catheter. No relationship was noted between disruption of voiding function and either age or gender. However, significant inverse correlation was observed between the age at disease onset and the time to CIC (r=-0.77, P=0.00001). CONCLUSIONS: These data suggest that the younger a patients is at HAM/TSP onset, the longer voiding function will be maintained.

The preventive effect of green tea on the gap junction intercellular communication in renal epithelial cells treated with a renal carcinogen.

OBJECTIVE: Clinical studies imply that (-)-epigallocatechin-3-gallate (EGCG), a main ingredient of green tea catechins, has a chemopreventive action against cancers and suppresses the proliferation of cancer cells. However, there is no report about its chemopreventive effect for renal cancer. We previously determined that renal carcinogens suppressed the gap junction intercellular communication (GJIC) of renal epithelial cells. In this study, we investigated the effect of EGCG on the GJIC of renal epithelial cells treated with a renal carcinogen. MATERIALS AND METHODS: Mardin-Darby canine kidney (MDCK) cells were used to determine the protective effects of EGCG on dimethylnitrosamine-induced alteration of GJIC and connexin 43 (Cx 43). The maximum concentration of EGCG was determined by the lactate dehydrogenase assay method. The scrape-loading dye transfer method was used to assess the expression and cellular localization of Cx 43. The phosphorylation status of Cx 43 was determined by Western blot analysis. RESULTS: The optimal noncytotoxic concentration of EGCG was determined to be 10 microg/ml. The levels of GJIC and Cx 43 expression were markedly decreased in MDCK cells exposed to dimethylnitrosamine. A 12-h pretreatment with EGCG greatly ameliorated the GJIC-inhibitory effects of dimethylnitrosamine. CONCLUSION: These results suggest that the preservation of GJIC may indicate the chemopreventive effect of green tea on renal epithelial cells treated with a renal carcinogen in vitro.

Upregulation of Angiotensin II Receptor and Connexin 43 in Increased Suburothelial Myofibroblasts in the Rat Inflammatory Bladder.

OBJECTIVES: Signaling pathways in suburothelial layer are involved in the bladder sensory response. The expression of angiotensin II type 1 (AT1) receptors and connexin 43 (Cx43) in suburothelial myofibroblasts was investigated in an acute bladder inflammation model. METHODS: Adult female Wistar rats underwent urethral catheterization and received 0.2 mL intravesical infusion of 0.4 M HCl to establish acute bladder inflammation model or 0.2 mL of sterile saline as control (n = 10 rats/group). Eight days after treatment, cystometry was performed. Suburothelial myofibroblasts were also collected and subjected to immunohistochemical staining to examine AT1 receptor and Cx43 expression. RESULTS: Eight days after treatment with HCl to induce acute bladder inflammation, the frequency and basal pressure of the bladder was significantly increased compared with those in control rats. The number of suburothelial myofibroblasts was significantly increased in acute bladder inflammation rats, as was the expression of AT1 receptor and Cx43. CONCLUSION: These results suggest that the increased number of suburothelial myofibroblasts, upregulation of AT1 receptor and Cx43 expression may be associated with the pathogenesis of hyperactivation of bladder sensory signaling pathways in acute inflammatory bladder.

Renoprotective effects of telmisartan after unilateral renal ablation in rats.

PURPOSE: The renoprotective function of the angiotensin II type 1 receptor blocker (ARB) is well-known in various studies, including the animal model of renal failure. However, detailed temporal changes of pathological and molecular findings after unilateral nephrectomy are not fully understood. The main purpose of this study was to clarify the renoprotective effects and pathological changes induced by the ARB in rat-remnant kidney (RK) tissues after unilateral nephrectomy, but not after a 5/6 nephrectomy. METHODS: Telmisartan, which is structurally and functionally unique among ARB, was used in this study. Three rat groups were examined: A) no ARB administrated (RK, n=21); B) continuous subcutaneous infusion of an ARB administrated (RK-ARB, n=21); and C) a sham-operated group (Sham). Renal function was evaluated by blood urea nitrogen (BUN) levels and creatinine clearance (Ccr). Fibrosis was evaluated by hydroxyproline levels and Masson's trichrome staining. Expressions of angiotensin II type 1 receptor (AT1R) and transforming growth factor beta (TGF-ß) were investigated by real-time polymerase chain reaction and Western blotting. RESULTS: There was no significant difference regarding body and kidney weight or pathological features evaluated by hematoxylin and eosin staining between the RK and RK-ARB groups. The Ccr in the RK group was significantly lower than that in the Sham group (P<0.01), but no significant difference was found between the RK-ARB and Sham groups. The fibrotic area increased significantly with time after nephrectomy in the RK group. Although a similar trend was found in the RK-ARB group, the percentage of fibrous area in the RK-ARB group was significantly lower than that in the RK group at each time point (P<0.01). AT1R mRNA levels in the RK group were regulated immediately compared with those in the RK-ARB group. Although expressions of the AT1R and TGF-ß were significantly higher in the RK-ARB group than in the Sham group, no significant differences were found between the RK-ARB and Sham group. CONCLUSION: The ARB had renoprotective effects after unilateral nephrectomy. The ARB effectively maintained Ccr. Our results also showed the possibility that fibrotic changes mediated by AT1R and TGF-ß play an important role in renal protection. Moreover, this is the first report on changes of AT1R expression after using the ARB telmisartan in kidney tissues after unilateral nephrectomy. Finally, our results suggest that ARB may be useful to prevent renal failure in patients treated with nephrectomy.

Expression of Angiotensin II Type 1 Receptor in Rat Bladder Smooth Muscle Cells in Response to a Streptzotocin Induced Diabetes Mellitus Model.

INTRODUCTION: The aim of this study was to investigate angiotensin II type 1 (AT1) receptors in rat bladder smooth muscle cells and alterations of AT1 receptors by diabetes mellitus and diuretic states. MATERIALS AND METHODS: Diabetes and diuresis were induced in adult female rats by a single intraperitoneal injection of streptozotocin and feeding 5% sucrose in water. Cystometry was performed on control, diuretic, and diabetic rats at 2 and 8 weeks after treatment. Immunohistochemical staining was used to detect expression of AT1 receptors in the bladder smooth muscle cell membrane. RESULTS AND CONCLUSIONS: In diabetic rats, expression of AT1 receptors in the bladder smooth muscle cell membrane increased at 2 weeks and further increased at 8 weeks. The local renin-angiotensin system in the rat bladder might be activated by the continuous hyperglycemia caused by intraperitoneal injection of streptozotocin administration.

Decreased cellular membrane expression of gap junctional protein, connexin 43, in rat detrusor muscle with chronic partial bladder outlet obstruction.

OBJECTIVES: To investigate alterations in gap junctional protein, connexin-43 (Cx-43), in the rat detrusor muscle with partial bladder outlet obstruction (P-BOO). Muscle cell actions, such as detrusor contractions, are thought to be synchronized by way of gap junctional intercellular communication. Gap junctions may play an important role in voiding, and P-BOO is a common medical problem. METHODS: A total of 33 female Wistar rats (12 weeks old) were divided into a P-BOO group and a sham-operated control group and were killed at 2, 4, and 8 weeks after surgery. Cystometric investigation, the alteration of gap junction, and Cx-43 protein expression, which compose the gap junction, were examined. RESULTS: The number of gap junctions was decreased in the P-BOO rat bladder. Furthermore, decreased cellular membrane expression of Cx-43 proteins was detected in rat detrusor muscle cells more than 4 weeks after surgery. The gap junctions of the detrusor muscle cell membranes were significantly fewer in number in the P-BOO rats with no detrusor contractions. CONCLUSIONS: These data suggest that the normal signals that contribute to voiding function could be transported directly through the gap junctions. Voiding dysfunction may be caused by the disruption of gap junctional intercellular communication.

Renal cell carcinoma with solitary metachronous metastasis to the urinary bladder.

We report a case of renal cell carcinoma with solitary metachronous metastasis to the urinary bladder occurring 6 years after radical nephrectomy. The patient was treated with partial cystectomy and survived for 60 months. Other cases like this one were reviewed in published reports, and the 3-year survival rate for patients with this type of cancer with solitary metastasis to the urinary bladder was found to be 80%. The follow-up duration of our case was the longest in the published studies. We suggest that urinary bladder metastasis of renal cell carcinoma should be resected because no effective treatment for metastatic renal cell carcinoma is available. A good prognosis may be expected, especially in patients with solitary metastasis to the urinary bladder.