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Effects of pelvic nerve neurectomy and estrogen on the M2 muscarinic receptor of the urinary bladder.

BACKGROUND: Normal physiological voiding, as well as generation of abnormal bladder contractions in the diseased state, is critically dependent on acetylcholine-induced stimulation of contractile muscarinic receptors on the detrusor muscle of the urinary bladder. This study investigated the effect of pelvic nerve neurectomy and estrogen treatment on the M2 muscarinic receptors of urinary bladder. METHODS: We studied the muscarinic cholinergic receptor density in the urinary bladder of castrated female rats following four weeks of estrogen treatment and/or pelvic nerve neurectomy. We used immunohistochemistry to detect the expression of M2 receptors on the smooth muscle cells of urinary bladder. RESULTS: When compared to a sham-operated group, the M2 receptors in the urinary bladders of rats that had undergone bilateral pelvic nerve neurectomy and estrogen treatment, showed no significant change. However, the M2 receptors decreased significantly in the urinary bladders of rats that had undergone simultaneous estrogen treatment and bilateral pelvic nerve neurectomy, when compared to the other groups (p < 0.05). CONCLUSION: Pelvic nerve denervation has a synergetic effect on the estrogen-induced down regulation of M2 receptor immunoreactive cells in the urinary bladder.

Animals↗

Staging urinary bladder cancer after transurethral biopsy: value of fast dynamic contrast-enhanced MR imaging.

PURPOSE: To evaluate contrast enhancement patterns of urinary bladder cancer and surrounding structures and to evaluate a fast dynamic first-pass magnetic resonance (MR) imaging technique in tumor and node staging and in differentiation of urinary bladder cancer from postbiopsy effects. MATERIALS AND METHODS: Sixty-one consecutive patients with histologically proved urinary bladder cancer were referred to undergo unenhanced and dynamic MR imaging 1-4 weeks after transurethral resection or biopsy. Subtraction and time (to beginning of enhancement) images were acquired. RESULTS: Results with unenhanced T1- and T2-weighted images were compared with those obtained with the unenhanced images plus dynamic contrast material-enhanced single-section turbo fast low-angle shot (FLASH) images. Urinary bladder cancer started to enhance 6.5 seconds +/- 3.5 (standard deviation) after the beginning of arterial enhancement, which was 4 seconds earlier than most other structures (postbiopsy tissue, 13.6 seconds +/- 4.2). In differentiation of postbiopsy tissue from malignancy on the basis of the beginning of enhancement depicted on time and subtracted images, accuracy improved from 79% to 90% (P < .02) and specificity improved from 33% to 92% (not significant). Overall, tumor staging accuracy improved significantly from 67% to 84% (P < .01) by adding the turbo FLASH images. CONCLUSION: Fast dynamic first-pass MR imaging, with at least one image acquired every 2 seconds, improved delineation of urinary bladder cancer, tumor staging, and detection of metastases.

Biopsy↗

[Carcinosarcoma of the urinary bladder].

A female patient is presented who had a large carcinosarcoma of the urinary bladder that became clinically manifest only 2 months before treatment. The initial treatment by transurethral resection was followed by radical cystectomy; 7 months postoperatively the patient died of local tumour recurrence with widespread metastases. Carcinosarcoma of the urinary bladder is a rare tumour with a poor prognosis. The majority of such tumours are not diagnosed until tumour growth is already far advanced. Owing to the small number of cases there is no clinically proven form of management. In contrast with superficial transitional cell carcinoma of the bladder, superficial carcinosarcoma of the bladder has always invaded the lamina propria, since in addition to the carcinomatous degeneration of the mucosa, sarcomatous degeneration of the underlying submucosal stroma is also present. Any local surgical treatment, such as TUR or partial cystectomy, involves the risk of incomplete tumor removal, because the sarcomatous elements typically invade the submucosa while the overlying mucosa remains intact. Therefore, radical cystectomy appears to be the treatment of choice for both superficial and invasive carcinosarcoma of the urinary bladder.

Carcinosarcoma↗

[Endoscopic operations in invasive cancer of the urinary bladder].

Long-term results of conservative treatment of 153 patients with invasive cancer of the urinary bladder were studied retrospectively. The patients had stage T2 (n=121, 79.1%), T3 (n=26, 17%), T4 (n=6, 3.9%). All the patients had transitional cell cancer. GI, G2 and G3 tumors were registered in 104 (68%), 35 (24%) and 12 (8%) cases, respectively. 88 (57.5%) patients received combined treatment, 65 (42.5%) patients--only surgery. In the patients with a small invasive tumor of the urinary bladder subjected to surgery alone (TUR-vaporization), overall 5-year survival was 70.4%. In patients with advanced cancer of the urinary bladder who had received curative radiotherapy in case of superficial residual tumor had TUR-vaporization of the urinary bladder overall 5-year survival was 76.5%. In patients exposed to large-fraction (TFD 20-25 Gy) preoperative radiotherapy followed by TUR-vaporization, survival at this moment was 84.6%. Three-year overall and recurrence-free survival at stage T2 was 97.5 and 47.4%, respectively; at stage T3 and T4 overall 3-year survival was 57.1 and 26.6%, respectively. Thus, the conclusion is that transurethral electrosurgery in conservative therapy of patients with invasive cancer of the urinary bladder is a promising approach.

Adult↗

Nonepithelial neoplasms of the urinary bladder.

Nonepithelial tumors are rare in the urinary bladder, but their exact classification is very important in the differential diagnosis between these tumors and epithelial lesions. In the new WHO classification and in the third series of the Armed Forces Institute of Pathology (AFIP) "Atlas of Tumor Pathology" on urinary bladder tumors, various mesenchymal tumors, mixed epithelial and mesenchymal tumors and myofibroblastic proliferations are summarized. In the following we will describe the histology, immunohistology, and cytogenetics of nonepithelial tumors and lesions.

Biomarkers, Tumor↗

[Proliferating character of inverted papilloma of the urinary bladder].

BACKGROUND: Inverted papilloma (IP) of the urinary bladder is generally considered to be a benign lesion by histological examination. In recent years, however, there have been several cases of IP simultaneously accompanied with transitional cell carcinoma (TCC), elsewhere in the bladder or combined as a single urothelial lesion. So we investigated proliferating character of IP by DNA ploidy analysis and immunohistostaining with proliferating cell nuclear antigen (PCNA). METHODS: Six cases of IP of the urinary bladder were analyzed and 12 cases of TCC of G1 and G3 grade were included in this study as a control. As DNA ploidy analysis, all specimens were feulgen stained using CAS DNA staining kit and examined by image cytometry (CAS 200R system). For the PCNA immunohistochemistry, all specimens were stained with anti-PCNA monoclonal antibody (Novocastra Lab.: PC10) according to ABC (avidin-biotin-complex) standard method. We determined that the DNA Index of the case under 1.20 was diploid and the others was aneuploid. PCNA staining were determined by only one pathologist as follows: negative (-) and positive (+), (2+) and (3+). RESULTS: As DNA ploidy, 5 of 6 cases of TCC G3 group as a control were aneuploid. But in spite of all cases of TCC G1 group were diploid, among IP cases, only 1 out of 6 was aneuploid. As PCNA staining, 2 of 6 in TCC G1 group and 5 of 6 in G3 group were positive. And it was noted examination was positive. CONCLUSION: There have been no recurrence since transurethral resection in all IP in the study including the case recognized as aneuploid and positive for PCNA staining. But the present results suggest that among IPs, considered generally as a benign tumor, the case which has high proliferating character exists.

Adult↗

[Palliative ileal conduit in inoperable cancer of the urinary bladder].

A retrospective study is presented of 19 patients with inoperable urinary bladder carcinoma in which urinary diversion was performed by ileal conduit without cystectomy. The postoperative mortality rate was 10.5% and the incidence of complications was 16%. The average time of survival was 5.1 months and varied from between one and 23 months. According to the literature these results are no better than those in patients undergoing no therapy at all. It is, thus, our opinion that palliative ileal conduit should not be considered a suitable method for urinary diversion in patients with advanced carcinoma of the urinary bladder.

Aged↗

Small cell carcinoma of the urinary bladder: a clinicopathologic analysis of 64 patients.

BACKGROUND: Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. Herein, the authors report a series of 64 patients with small cell carcinoma of the urinary bladder. METHODS: Histologic slides and medical records from 64 patients with small cell carcinoma of the urinary bladder were reviewed for morphologic, demographic, and clinical data. All patients fulfilled the criteria established for small cell carcinoma according to the World Health Organization classification system. The 2002 tumor, lymph node, and metastasis (TNM) system was used for pathologic staging. The correlations of various clinicopathologic characteristics with survival were analyzed. RESULTS: Patients ranged in age from 36 years to 85 years (mean age, 66 years). The male-to-female ratio was 3.3:1.0. Among patients with clinical information available, 65% had a history of cigarette smoking, and 88% presented with hematuria. All but one patient had muscle-invasive disease at presentation. Thirty-eight patients (59%) underwent cystectomy. Sixty-six percent of patients had lymph node metastasis at the time of cystectomy. Twenty patients (32%) had pure small cell carcinoma, and 44 patients (68%) had small cell carcinoma with other histologic types (35 patients had urothelial carcinoma, 4 patients had adenocarcinoma, 2 patients had sarcomatoid urothelial carcinoma, and 3 patients had both adenocarcinoma and urothelial carcinoma). With a mean follow-up of 21 months, 68% of patients died of bladder carcinoma. None of the clinicopathologic parameters studied (age, gender, presenting symptoms, smoking history, the presence of a nonsmall cell carcinoma component, chemotherapy, or radiation therapy) were associated with survival. No significant survival difference was found between patients who did and did not undergo cystectomy (P = 0.65). Patients who had organ-confined disease had marginally better survival compared with patients who had nonorgan-confined disease (P = 0.06). The overall, 1-year, 18-month, 3-year, and 5-year disease-specific survival rates were 56%, 41%, 23%, and 16%, respectively. CONCLUSIONS: The prognosis for patients with small cell carcinoma of the urinary bladder remains poor, even though the overall survival for patients with bladder carcinoma has improved significantly over the last decade.

Adenocarcinoma↗

Expression of cyclooxygenase-2 in human transitional cell carcinoma of the urinary bladder.

Recent studies suggest that expression of cyclooxygenase-2 (Cox-2) is elevated in transitional cell carcinoma (TCC) of the urinary bladder and that inhibition of Cox-2 activity suppresses bladder cancer in experimental animal models. We have investigated the expression of Cox-2 protein in human TCCs (n = 85), in in situ carcinomas (Tis) of the urinary bladder (n = 17), and in nonneoplastic urinary bladder samples (n = 16) using immunohistochemistry. Cox-2 immunoreactivity was detected in 66% (67 of 102) of the carcinomas, whereas only 25% (4 of 16) of the nonneoplastic samples were positive (P: < 0.005). Cox-2 immunoreactivity localized to neoplastic cells in the carcinoma samples. The rate of positivity was the same in invasive (T1-3; 70%, n = 40) and in noninvasive (Tis and Ta; 65%, n = 62) carcinomas, but noninvasive tumors had a higher frequency (32%) of homogenous pattern of staining (>90% of the tumor cells positive) than the invasive carcinomas (10%) (P: < 0.05). However, several invasive TCCs exhibited the strongest intensity of Cox-2 staining in the invading cells, whereas other parts of the tumor were virtually negative. Finally, strong Cox-2 positivity was also found in nonneoplastic ulcerations (2 of 2) and in inflammatory pseudotumors (2 of 2), in which the immunoreactivity localized to the nonepithelial cells. Taken together, our data suggest that Cox-2 is highly expressed in noninvasive bladder carcinomas, whereas the highest expression of invasive tumors associated with the invading cells, and that Cox-2 may also have a pathophysiological role in nonneoplastic conditions of the urinary bladder, such as ulcerations and inflammatory pseudotumors.

Adult↗

Decreased expression of G protein-coupled receptor kinases in the detrusor smooth muscle of human urinary bladder with outlet obstruction.

AIM: We examine the expression of mRNA of G protein-coupled receptor kinase (GRK) subtypes and muscarinic acetylcholine receptor (M) subtypes in the detrusor smooth muscle of the human urinary bladder. Furthermore, we confirm the presence and the localization of GRK proteins in the detrusor smooth muscle of the obstructed bladder in comparison with the control bladder. METHODS: Detrusor smooth muscle tissues of the human urinary bladder were obtained from 12 male patients; 6 patients did not have bladder outlet obstruction, and the other 6 patients had bladder outlet obstruction. Portions of the dome or anterior wall of the urinary bladder were used for the present study. Reverse transcription/polymerase chain reaction for GRK2, M2 and M3 was performed using total RNA extracted from human urinary bladder detrusor. Antibodies to GRK2, GRK3 and GRK4 were used to confirm the presence of the protein product in the human urinary bladder using immunohistochemical staining and the western blotting technique. RESULTS: All complementary DNA (cDNA) transcribed from three different mRNA (M2, M3 and GRK2) were successfully amplified and size-fractionated. The expression of GRK2 protein was strong in the human bladder detrusor, but was significantly weakened by western blotting in obstructed bladder in comparison with control bladder. CONCLUSIONS: Failure in desensitization mechanisms of muscarinic acetylcholine receptors might be related to storage symptom elicited by overactivity in obstructed bladder with benign prostatic hyperplasia.

Blotting, Western↗

[Four cases of spontaneous rupture of the urinary bladder].

Between November 1997 and March 2001, 4 female patients from 44 to 65 years of age with a spontaneous rupture of the urinary bladder were analyzed. They complained of abdominal pain and had undergone an intra-pelvic gynecological operation (3 for uterine cancer, 1 for an ovarian cyst) several years before. The three with uterine cancer had also received radiation therapy. For their present condition, spontaneous urinary bladder rupture, their treatment was indwelling a urethral catheter. Two of them have had no recurrence of urinary bladder rupture after one month since having the urethral catheter indwelt. One, however, had to have the catheter re-indwelt due to unsuccessful suturing of the urinary bladder wall. The fourth patient had bilateral nephrostomy tubes due to severe radiation cystitis. Thus, one can infer that intra-pelvic gynecological operations and radiation therapy are major factors causing spontaneous urinary bladder rupture. While indwelling a urethral catheter may be effective for some patients with a spontaneous rupture of the urinary bladder, it may be very difficult to treat more complicated cases.

Adult↗

[The role of preserving therapy of invasive cancer of the urinary bladder].

Cystectomy in the treatment of invasive cancer of the urinary bladder is not the only therapeutic modality in this pathology. In selected patients an alternative exists--transurethral resection of the urinary bladder followed by adjuvant concurrent chemotherapy and radiotherapy. The preserving therapy can be recommended to patients over 60 years of age in the presence of a low-grade solitary tumor of a mobile wall of the urinary bladder respectable with preservation of the organ capacity.

Adult↗

[A case of xanthogranuloma of the urinary bladder].

A case of xanthogranuloma of the urinary bladder is reported. A 68-year-old man was referred to our hospital for the evaluation of microscopic hematuria. At that time, he did not have an abdominal tumor and ultrasonography showed no abnormality of the kidneys and the bladder wall. Two months later, he was admitted with the chief complaints of perineal discomfort and non tender fist size mass was palpable in the lower abdomen. Ultrasonography, computed tomographic scan and magnetic resonance imaging MRI demonstrated a supravesical mass which was strongly suspected as urachal tumor. Total cystectomy with urachal resection was performed. The histological diagnosis was xanthogranuloma. The patient has been in good health without recurrence, 4 years after surgery. We discuss xanthogranuloma of the urinary bladder in the literature.

Aged↗

Differential coupling of muscarinic M1, M2, and M3 receptors to phosphoinositide hydrolysis in urinary bladder and longitudinal muscle of the ileum of the mouse.

We investigated the coupling of muscarinic receptor (M) subtypes to phosphoinositide hydrolysis in ileum and urinary bladder using muscarinic receptor knockout mice. In urinary bladder from wild-type mice, the muscarinic agonist oxotremorine-M, elicited a robust phosphoinositide response characterized by an EC50 value of 0.22 microM and a maximal response (Emax) of 32.8% conversion of [3H]inositol-labeled phosphoinositides into [3H]inositol phosphates. A similar response was observed in urinary bladder from M2 knockout mice, whereas no measurable response was observed in urinary bladder from M3 and M2/M3 knockout mice. In ilea from wild-type and M2 knockout mice, substantial phosphoinositide responses to oxotremorine-M were measured, characterized by EC50 values of 0.37 and 0.52 microM and Emax values of 35.8 and 34.7%, respectively. Oxotremorine-M also elicited phosphoinositide hydrolysis in ilea from M3 and M2/M3 knockout mice, although these responses were less sensitive (EC50 values of 1.6 and 1.4 microM; Emax values of 31.2 and 20.8%, respectively). The response in ileum from the M2/M3 knockout was significantly smaller than that from the M3 knockout. The muscarinic phosphoinositide response in ilea from M2/M3 knockout mice originated in the smooth muscle and exhibited a profile for competitive antagonism consistent with an M1 mechanism. These data suggest a major role for the M3 receptor in eliciting phosphoinositide hydrolysis in the ileum and urinary bladder and minor roles for the M1 and M2 in ileum.

Algorithms↗

T-cell abnormality and defective interleukin-2 production in patients with carcinoma of the urinary bladder with schistosomiasis.

Patients with schistosomiasis of the urinary bladder (SB) and schistosomiasis with carcinoma of the urinary bladder (SCB) had significantly increased percentage of IL-2R-, HLA-DR-, and transferrin receptor (T9)-bearing T cells in circulation. The percentage of these activated T cells decreased by in vitro culture with PHA but increased by Schistosoma haematobium soluble egg antigen. These patients with SB and SCB had a PHA-specific defect in IL-2 production. A functional defect with induction of IL-2R-positive suppressor monocytes appears to correlate with the defective PHA-induced IL-2 production by CD4+ T cells and monocytes. Disordered regulation of PHA-induced IL-2 production by the CD4+ T cells and monocytes may be the key feature in the highly depressed cell-mediated immune response in schistosomiasis. However, immune activation and significantly elevated IL-2 production in response to disease-specific S. haematobium soluble egg antigen may be related with the pathogenesis of SB and SCB. Thus, S. haematobium-specific CD4+ T cells are present in schistosomiasis, and their function is determined by adequate release of IL-2-and/or IL-2R-bearing CD11+ suppressor monocytes.

Adult↗

Adrenergic and cholinergic innervation of the rag urinary bladder.

The autonimic innervation of the rat urinary bladder was studied using histochemical methods and nerve stimulations. A sparse adrenergic innervation of the detrusor muscle was found. It was supposed to originate from long adrenergic neurones. The trigonum area had a rich ssupply of adrenergic fibres, probably derived from short adrenergic neurones. A uniformly rich supply of acetylcholine-esterase (AChE)-positive nerves was found in the WHOLE BLADDER. Postganglionic sympathetic denervation caused no detectable change of adrenergic or AChE-positive nerves in the bladder, while parasympathetic decentralization or denervation produced a total disappearance of adrenergic fibres. The AChE-positive nerves were appreciably reduced in number after parasympathetic decentralization and not detectable after postganglionic denervation. Neither adrenergic nor AChE-positive ganglion cells could be demonstrated in the bladder wall. Electrical stimulation of the hypogastric nerves or the pelvic nerves distal to the pelvic ganglia elictied contraction of the detrusor muscle. The responses were not affected by hexamethonium, dihydroergotamine or proparanolol but were slightly reduced by guanethidine, reduced to about 40% by atropine and potentiated by eserine. Stimulation of the pelvic nerve proximal to the pelvic ganglion was partially blocked by hexamethonium. It si concluded that the urinary bladder of the rat is supplied by postganglionic adrenergic fibres mainly via the pelvic nerves and only to a lesser extent via the hypogastric nerves. Probably cholinergic fibres pass to the bladder mainly via the pelvic nerves but also via the hypogastric nerves, having their cellbodies outside the bladder wall, partly proximal to the pelvic ganglia.

Acetylcholinesterase↗

Hyperplasia and hypertrophia in the denervated and distended rat urinary bladder.

The parasympathetically denervated and distended rat urinary bladder was found to have increased fourfold in weight when examined 3 weeks postoperatively. Both in muscularis and mucosa of such a bladder the synthesis of proteins, RNA and DNA was increased severalfold. An increase in the polyamines putrescine, spermidine and spermine was also found; these polyamines are usually linked to protein synthesis. The results suggest that the cells of the two layers increase both in size and number. Hyperplasia was, in a previous study, suggested as a possible explanation for a right-ward shift of the active length-tension curve of muscle strips in the denervated rat urinary bladder.

Animals↗