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c-kit Expression in small cell carcinoma of the urinary bladder: prognostic and therapeutic implications.

The prognosis for small cell carcinoma of the urinary bladder is poor, and strategies for improved therapy are needed. Targeted therapy against the c-kit proto-oncogene has been successful in the management of gastrointestinal stromal tumor. We investigated the expression of c-kit in 52 cases of small cell carcinoma of the urinary bladder. Specimens with more than 10% of cells demonstrating strong membrane staining were considered to have positive immunostaining for c-kit. c-kit expression was detected in 21 of 52 specimens from these patients. Among the 21 specimens, seven had less than 10% staining, and were considered to be negative. Nine had 11-50% staining, and five had more than 50% staining. Overall, 14 of 52 (27%) small cell carcinomas of the urinary bladder were positive for c-kit expression. During a median follow-up of 11 months, 60% of the patients died of bladder cancer. No association was found between c-kit expression and survival or other clinicopathologic parameters. Five-year cancer-specific survivals for c-kit-positive and c-kit-negative tumors were 9 and 15%, respectively (P=0.36). A significant proportion (27%) of small cell carcinomas of the urinary bladder expressed c-kit, suggesting that it may prove useful as a therapeutic target in small cell carcinoma of the urinary bladder.

Adult↗

Vascular plexus is a differentation criterion for muscularis mucosa from muscularis propria in small biopsies and transurethral resection materials of urinary bladder?

OBJECTIVE: Smooth muscle fibres are found within the superficial lamina propria of urinary bladder (Muscularis Mucosa). These muscle fibres of muscularis mucosa should be distinguished from the muscularis propria in cases with urothelial carcinoma, because the depth of infiltration affects prognosis and therapy modalities. The aim of the present study was to evaluate whether the presence of vascular plexus is a criterion for muscularis mucosa and to distinguish it from muscularis propria in urinary bladder biopsies and transurethral resection specimens. MATERIALS AND METHODS: Hematoxylin-Eosin and Masson-Trichrome stained slides of 54 cases with urothelial carcinoma were reviewed. RESULTS: In all cases (100%), thick walled vessels were observed within the lamina propria of urinary bladder. Smooth muscle layer of lamina propria was seen in 48 of 54 cases (88.8%), and these smooth muscle fibres were co-existed with thick walled vessels. In invasive urothelial carcinoma; thin smooth muscle fibres and thick walled vessels were seen within the lamina propria in 22 of 24 cases (91.7%). There were two cases (8.3%) including only vessels in small biopsies of invasive urothelial carcinoma cases. In cases with non-invasive urothelial carcinoma; muscle fibres of muscularis mucosa and vessels were found within the lamina propia in 26 of 30 cases (86.7%). In this group, muscle fibres were not detected in 4 cases (13.3%). CONCLUSION: Muscularis mucosa can be detected histologically in urinary bladder biopsies and TUR materials. We emphasize that the presence of vascular network is a useful criterion to determine muscularis mucosa of urinary bladder, even in the absence of muscle fibres.

Blood Vessels↗

Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder.

Intestinal metaplasia has been proposed to be a precursor lesion of adenocarcinoma in the urinary bladder. CDX2 is a transcription factor that is encoded by a homeotype gene that plays an essential role in the differentiation and proliferation of intestinal epithelial cells. Hepatocyte-specific antigen (Hep) has also been shown to be a useful marker of intestinal metaplasia. Tissues from 46 patients, including 22 cases of intestinal metaplasia of the urinary bladder, 11 cases of typical cystitis glandularis, and 13 cases containing both lesions, were selected and immunohistochemical stains for CDX2, Hep, cytokeratin 20 (CK20), and cytokeratin 7 (CK7) were performed. Nuclear staining for CDX2 was observed in 29 of 35 (83%) cases of intestinal metaplasia of the urinary bladder. In contrast, nuclear staining for CDX2 was not observed in any case of typical cystitis glandularis; however, seven of 24 (29%) cases showed aberrant cytoplasmic expression in a mean of 37% of cells. CK20 was expressed in 28 of 35 (80%) cases of intestinal metaplasia, but was observed in only one of 24 (4%) cases of cystitis glandularis in 15% of cells. CK7 was expressed in only six of 35 (17%) cases of intestinal metaplasia, whereas expression of CK7 was observed in all cases (100%) of typical cystitis glandularis with a mean percentage of positively staining cells of 63%. The mean percentages of positively staining cells in intestinal metaplasia with CDX2, CK20, and CK7 were 55, 49, and 53%, respectively. All examples of both intestinal metaplasia and typical cystitis glandularis were uniformly negative for Hep. In the urinary bladder, intestinal metaplasia and typical cystitis glandularis have sharply contrasting immunoprofiles. Additionally, the absence of Hep staining in intestinal metaplasia of the urinary bladder, despite its morphologic resemblance to normal colonic mucosa and intestinal metaplasia in other organs, may signify the presence of unique metaplastic pathways in the urinary bladder.

Autoantigens↗

Characteristics of proton excretion in normal and acidotic toad urinary bladder.

This study, performed on the urinary bladder of Bufo marinus, was to investigate the characteristics of H+ excretion in the normal and metabolic acidotic toad. Experiments were run in modified Ussing chambers in the presence and absence of exogenous CO2. Amiloride in the mucosal medium (1.5 X 10(-4) M) inhibited H+ excretion in the acidotic bladder but this inhibition was reversed in the presence of 5% CO2. Na+-free mucosal medium revealed a component of H+ excretion in the normal toad that is Na+-dependent and not reversed by 5% CO2. Acetazolamide (10(-3) M) had no effect on H+ excretion in normal toad but inhibits excretion in the acidotic toad both in the presence and absence of exogenous CO2. In both the presence and absence of exogenous CO2 and in the presence of varying pH gradients, the bladders from acidotic toads excreted H+ at a greater rate and were able to generate greater pH gradients than in normal bladders. Voltage clamp experiments revealed that H+ excretion in the acidotic toad was inhibited by a mucosal potential difference of -20 to -100 mV but this inhibition was completely reversed by 5% CO2. In the normal toad bladder H+ excretion was stimulated by a mucosal potential difference of -20 to -100 mV in both the presence and absence of exogenous CO2. Our evidence suggests the possibility of two H+ excretory mechanisms in toad urinary bladder each with its' own set of characteristics dependent on the acid-base state of the animal. Proposed models are presented for these mechanisms.

Acidosis↗

[Comparative microscopic anatomy of the urinary bladder of various domestic and wild ruminants].

The Authors focus their interest on the microanatomical differences between urinary bladders of some domestic (sheep and cattle) and wild Ruminantia (roe and chamois). Sixteen urinary bladders of the following species have been studied by Azan, Masson and Weigert staining methods: Three urinary bladders of Ovis aries (L.) and Bos taurus (L.) drawn from animals of both sexes; seven urinary bladders drawn from female of Capreolus capreolus (L.); three urinary bladders from both sexes specimens of Rupicapra rupicapra (L.). It is possible to summarize the data on the compared microanatomy of urinary bladder in the following way: it presents three tunics: mucosa, muscularis and adventitia. The tunica mucosa is composed of lamina propria and transitional epithelium, and presents typical plicae which give a peculiar aspect to the lumen. In roe deer the lamina propria presents several smooth muscle fibers which are organized in an evident "muscularis mucosae" which is absent in all the studied species. The tunica muscularis is composed of two longitudinal (outer and inner) muscle layers and a middle circular layer. In roe this tunica is thicker and more powerful than in other species, and the single layers are more evident because of the presence of many connective septa. The tunica adventitia is composed of loose connective tissue, and some elastic fibers. Unexpectedly, the Chamois, which belongs to wild Ruminants as the roe, does not present a "muscularis mucosae". Therefore the authors suppose that the presence of "muscularis mucosae" in roe could be due to the ethology peculiar of this species which is accustomed to mark the boundary of its territory by staling frequently.

Animals↗

[Effects of propiverine hydrochloride (propiverine) on isolated rat and dog urinary bladder].

Propiverine is a drug for the treatment of incontinence and pollakiuria. The effects of propiverine on isolated rat and dog urinary bladder were investigated. At doses of 10(-6)-3 x 10(-5) M, propiverine caused both a rightward shift and inhibition of the maximum response in the acetylcholine (ACh) dose-response curve. The pA2 values for rat and dog urinary bladder were 5.97 and 6.62, respectively. At doses of 10(-5)-10(-5) M, propiverine also dose-dependently inhibited KCl (100 mM)-induced contractions. The IC50 values for rat and dog urinary bladder were 3.9 x 10(-6) M and 3.8 x 10(-6) M, respectively. The pA2 value and the IC50 value of terodiline for rat urinary bladder were 6.08 and 6.6 x 10(-6) M, respectively. In contrast, the pA2 value and the IC50 value of oxybutynin for rat urinary bladder were 7.69 and 4.5 x 10(-6) M, respectively, suggesting that oxybutynin exerts an anti-muscarinic effect at doses at which no discernible anti-KCl effect was observed, whereas propiverine and terodiline exerted both effects at the same doses. The inhibitory effect of drugs on the contraction induced by electrical field stimulation was tested. At a dose of 10(-7) g/ml, tetrodotoxin inhibited the contraction of rat and dog urinary bladder by 76.6% and 92.6%, respectively. Propiverine and verapamil dose-dependently inhibited the contractile response induced by electrical field stimulation at doses of 10(-5) M or more and 3 x 10(-6) M or more, respectively. At these concentrations, a marked anti-KCl effect of the drugs on smooth muscle was observed. On the other hand, atropine caused no inhibition of the contractile response in rat urinary bladder at a dose of 3 x 10(-5) M, and it inhibited the contraction in dog urinary bladder by 14.9% at a dose of 10(-5) M. These findings suggest that although propiverine exhibits both anti-muscarinic and anti-KCl effects in isolated rat and dog urinary bladder, the inhibitory effects of propiverine on the atropine-resistant part of contraction may be mainly due to its anti-KCl effect.

Acetylcholine↗

Urinary bladder pathology 2004: an update.

The field of urinary bladder pathology is advancing at a rapid rate, with generation of significant new knowledge on molecular pathogenesis and cell and tissue-based diagnosis. The aim of this presentation is to survey selected, recent advances in this broad field, with specific focus on histologic typing, grading, staging, molecular classification, and reporting on neoplasia of the urinary bladder.

Carcinoma↗

Vasoactive intestinal polypeptidergic innervation of human urinary bladder in normal and pathological conditions.

Urinary bladder biopsies from 31 multiple sclerosis patients, 9 diabetics, 5 patients after transtrigonal phenolization and 20 control patients were stained for acetylcholinesterase, S100 and vasoactive intestinal polypeptide (VIP). The VIP immunoreactivity was not decreased in all neuropathic bladders and its depletion was not related to cholinergic depletion. There was no correlation between bladder over- or underactivity and VIP content. VIP can act as a modulator of detrusor function in normal conditions. The significance of its depletion in neurogenic bladders needs further elaboration.

Acetylcholinesterase↗

Experimental evaluation of urinary bladder marsupialization in male goats.

OBJECTIVE: To evaluate the outcome of urinary bladder marsupialization in male goats. STUDY DESIGN: Prospective, experimental study. ANIMALS: Six healthy mixed-breed male goats. METHODS: After experimentally induced urethral obstruction, 6 male goats had urinary bladder marsupialization. Renal ultrasonography, complete blood count, and serum biochemical analysis were evaluated preoperatively (day 0), at 7 postoperative days, and then at 30-day intervals until 180 days. Stomal diameter was recorded immediately postoperatively and at each postoperative interval. Necropsy examination was performed on day 180 or when stomal stricture or death occurred. RESULTS: Stomal stricture occurred in 1 goat at 120 days. Another goat was found dead at 150 days; severe, suppurative cystitis was identified on necropsy. All goats had mild urine scald dermatitis. Serum biochemical values remained within normal limits, but significant decreases in white blood cell count, serum creatinine concentration, and stomal diameter occurred. At necropsy, all bladders were tubular in shape. Histological evidence of chronic suppurative cystitis and chronic, mild lymphoplasmacytic pyelitis occurred in all goats. Bacterial culture of renal tissue yielded growth in 3 goats, and bladder mucosal swabs yielded bacterial growth in all goats. CONCLUSIONS: Although clinical signs of ascending urinary tract infection were not observed in goats with patent stomata, urinary bladder marsupialization may result in ascending urinary tract inflammation or infection. CLINICAL RELEVANCE: Based on our results, urinary bladder marsupialization should be recommended with caution as the primary method for management of urinary tract obstruction in clinical cases.

Animals↗

Noradrenergic fibers in the Pacinian corpuscles of the cat urinary bladder.

Pacinian corpuscles in the cat urinary bladder were studied using the hematoxylin and eosin staining, formaldehyde-induced fluorescence histochemistry, immunohistochemistry for tyrosine hydroxylase (TH) and immunoelectron microscopy. The existence of catecholaminergic nerve fibers penetrating into the corpuscles was clarified. (1) About 10 Pacinian corpuscles which were mainly located in the subserosa were found in the lower one-third portion of each urinary bladder. (2) One or two corpuscles containing blue-green fluorescent fibers were detected in each bladder. These fibers were equivalent to TH-immunopositive varicose fibers using the avidin-biotin-peroxidase complex method. (3) Thin nerve fibers containing dense-cored vesicles were found in the corpuscle by immunoelectron microscopy. These fibers spirally encompassed a swollen sensory terminal at a distance in the inner core. According to the above findings, we discuss a modulatory function of the catecholaminergic fibers in this mechanoreceptor.

Adrenergic Fibers↗

Contiguous but dissimilar epithelial neoplasms of the urinary bladder.

An unusual tumour of the urinary bladder is described. It consists of two distinct nodules each with a quite different histological appearance, one being mucus-secreting adenocarcinoma, the other transitional cell carcinoma. Where the nodules are in contact there is little intermingling of the two histological patterns and it is suggested that the findings are probably due to the collision of two separate neoplasms. Metaplastic changes are present in the bladder mucosa adjacent to the tumour. The significance of these changes in the pathogenesis of adanocarcinoma is discussed.

Adenocarcinoma, Mucinous↗

The efficacy of preoperative systemic chemotherapy in the local control of muscle-invasive transitional cell carcinoma of the urinary bladder.

Transitional cell carcinoma of the urinary bladder has a poor prognosis, once the muscle layers of the bladder wall have been invaded, irrespective of whether operative or radiation therapy is chosen for local treatment. The main reason for this is probably the existence of disseminated micrometastases at the time of primary treatment. Thus, a combination of systemic and local treatment would seem logical. The present study reports the response to chemotherapy in 30 patients with muscle-invasive urinary bladder tumours and the findings at subsequent cystectomy. The chemotherapy comprised cisplatin, methotrexate and leucovorin rescue and was tolerated without any alarming side-effects or increase in perioperative morbidity or mortality. The complete response rate was 43% (13/30) and, in 27% (8/30), there was a partial response with conversion into a more superficial tumour stage. The total, beneficial response rate was thus 70%.

Adult↗

Oat cell carcinoma of urinary bladder.

Oat cell carcinoma of the urinary bladder is extremely uncommon. There have been 52 reported cases in world literature to date. On light microscopic, histochemical, and ultrastructural grounds, these tumors are similar to oat cell carcinoma of the bronchus and other extrapulmonary oat cell carcinomas. Furthermore, they may be grouped together as a clinical entity characterized by an aggressive clinical course with early and extensive metastases, and partial remission with certain chemotherapeutic agents. We report a case of primary small cell carcinoma of the urinary bladder in a forty-two-year-old man and review previous reports with similar histology. The importance of establishing this diagnosis and the optimum forms of therapy are discussed.

Adult↗

An approach to the classification of spindle cell proliferations in the urinary bladder.

Spindle cell proliferations of the urinary bladder are uncommon but may cause significant diagnostic difficulty resulting from the degree of morphologic overlap between clinically benign and malignant lesions. These difficulties may be amplified in small biopsies because some of the more specific diagnostic features may not be present for evaluation. In addition, the number of different diagnostic terms applied to the same entity has added confusion to this diagnostic area. This review discusses the nomenclature, morphologic criteria, and immunohistochemical features used to classify spindle cell proliferations occurring in the urinary bladder, including those with myofibroblastic, smooth muscle, skeletal muscle, epithelial (sarcomatoid urothelial carcinoma), fibroblastic, and neural differentiation. A separate discussion of 5 challenging differential diagnostic scenarios is also presented.

Animals↗

[Correlative relationships between the microangioarchitectonics and histomechanics of the human urinary bladder].

The intraorganic blood bed in the human urinary bladder walls is a multilayer vascular plexus with a morphofunctional specificity of microcirculatory construction in every layer. In the formation of architectonic features and structure of the microcirculatory parts of the urinary bladder wall, is phase activity (alternate filling and emptying) plays an important role. A suggestion is made that large arterial and venous plexus with peculiar constraction presenting in the most important urodynamic sections (in the ureteral orifice and in the ureteral segment of the urinary bladder) perform not only trophic function, but also actively participate in urodynamics of these parts.

Adolescent↗

[Urinary bladder nuclear cytology: results of karyometric investigations].

To assess the value of nuclear morphometry in the cytological diagnosis of urinary bladder carcinoma, washouts of the urinary bladder from 168 patients with histological established bladder cancer were studied. Morphometrical measurements were done on the nuclei of the exfoliated cells. This retrospective study showed that the nuclear parameter obtained by automated image analysis may be helpful in the differential diagnosis between neoplastic and non-neoplastic urinary bladder disease and correlate fairly with the classic histologic grading of malignancy in transitional cell carcinoma of the urinary bladder.

Cell Nucleus↗

The effects of uranyl ions on neuromuscular transmission in the urinary bladder of the normal and streptozotocin-diabetic mouse.

The depressant effects of uranyl nitrate on the nerve-evoked muscle contraction of urinary bladder isolated from normal and streptozotocin-diabetic mice were compared. The non-cholinergic component of the evoked bladder contraction (in the presence of atropine) was specifically sensitive to the suppressive effect of uranyl nitrate. In contrast, the cholinergic component remaining after treatment with alpha, beta-methylene ATP was rather insensitive to uranyl nitrate. The contractile responses induced by KCl, acetylcholine and ATP were also not affected by uranyl nitrate, indicating a presynaptic site of action. High Ca2+ and calmodulin inhibitors (trifluoperazine, diltiazem and W7) antagonized the suppressive effects of uranyl ions. These results suggest that the depressant effects of uranyl nitrate is mediated by a reduction of prejunctional non-cholinergic transmitter release through the calcium-calmodulin pathway. In contrast to the normal bladder, the urinary bladder of streptozotocin-diabetic mice revealed not only weaker neurogenic contractile responses to electrical field stimulation, but also a profound reduction in the depressant effect of uranyl nitrate. These findings suggest that the Ca2+ regulation of non-cholinergic neurotransmission in mouse urinary bladder may be impaired in the diabetic state.

Animals↗