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Cure of undifferentiated small cell carcinoma of the urinary bladder with M-VAC chemotherapy.

Small cell carcinoma (SCC) of the urinary bladder is a rare, aggressive malignancy with approximately 135 cases reported in the literature. Treatments have included chemotherapy, radical surgery, radiotherapy, and combinations of these. We present the apparent cure of a 73-year-old man who presented with clinical stage T2 SCC of the urinary bladder. He was treated with three cycles of methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin (M-VAC) chemotherapy. Subsequent radical cystoprostatectomy revealed no pathologic evidence of tumor. The patient is alive and well with no evidence of recurrence 3 years post cystectomy. A brief review of the literature is also presented.

Journal Article↗

Apical membrane permeability and kinetic properties of the sodium pump in rabbit urinary bladder.

Previous studies have shown that aldosterone stimulates the rate of Na+ transport across the rabbit urinary bladder epithelium by increasing the apical membrane permeability to Na+. Paradoxically, ion-sensitive and conventional micro-electrode measurements demonstrated that intracellular Na+ activity aiNa+ was essentially unchanged by aldosterone, i.e. aiNa+ was constant regardless of the rate of Na+ transport. The present study was designed to resolve this apparent contradiction. The effects of elevated, endogenous aldosterone levels produced by low-Na+ diet (Lewis & Diamond, 1976) on urinary bladder Na+ transport were investigated in vitro using Ussing-type chambers and intracellular conventional and ion-sensitive microelectrodes. Apical membrane selectivity and kinetics of the Na+ pump were assessed as a function of hormone stimulation. The aldosterone-stimulated increase in Na+ transport was accounted for by increases in both the relative selective permeability of the apical membrane to Na+ and an increase in its absolute Na+ permeability. The kinetics of the Na+ pump were evaluated electrically by loading the cells with Na+ (monitored with Na+-sensitive micro-electrodes) or alternatively by manipulating serosal solution K+ concentration and measuring changes in the basolateral membrane electromotive forces and resistance. From these measurements the current generated by the pump was calculated as a function of intracellular Na+ or extracellular K+. The kinetics of the pump were not altered by aldosterone. A model of highly co-operative binding estimated Km for Na+ as 14.2 mM and 2.3 mM for K+. Hill coefficients for these ions were 2.8 and 1.8, respectively, consistent with a pump stoichiometry of 3 Na+ to 2 K+. The kinetic properties of the Na-K pump indicate that physiological levels of aiNa+ are poised at the foot of a step kinetic curve which energetically favours Na+ extrusion.

Aldosterone↗

[A case of asynchronous quadruple cancer arising from the prostate, stomach, rectum and urinary bladder].

Herein, we report a case of quadruple cancer arising from the prostate, stomach, rectum and urinary bladder. A 92-year-old man was admitted to our hospital on March, 1996, with complaints of macroscopic hematuria and micturition pain. He had a history of prostate cancer (no details) at the age of 67, and subtotal gastrectomy for gastric cancer (tubular adenocarcinoma, conclusive stage Ia) at the age of 89. He underwent a polypectomy for rectal cancer (well-differentiated adenocarcinoma)2 at the age of 90. There was no evidence of local recurrence or metastasis of these three carcinomas. Cystoscopy revealed multiple papillary tumors which were resected transurethrally. At the same time transrectal needle biopsy of prostate was performed. Pathology revealed transitional cell carcinoma G2 of urinary bladder and well differentiated adenocarcinoma of prostate. The postoperative course was uneventful and the patient has been doing well without recurrence of bladder cancer during the follow-up period of six months.

Adenocarcinoma↗

Tumor progression and expression of matrix metalloproteinase-2 (MMP-2) mRNA by human urinary bladder cancer cells.

Tumor cells at the stage of tumor progression build up a high tolerance to intrinsic and extrinsic defence systems and/or therapeutic procedures, and the cells deeply infiltrate the adjacent tissue, which is followed by tumor metastasis to remote organs and tissues. This study was designed to investigate the relationship between expression of matrix metalloproteinase-2 (MMP-2) and invasiveness of human bladder cancer cells, using cell lines derived from a parental human urinary bladder tumor cell line, T24. Two subpopulations of the human bladder cancer cell line T24, Hi-T24 and Lo-T24, were selected using an invasion assay and then expression of MMP-2 mRNA and protein was analyzed by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme immunoassay (EIA). The gross morphology, cell growth rate, and adhesion activity to a basement membrane extract (matrigel) of the high-invasive Hi-T24 cells were similar to those of the low-invasive Lo-T24 cells, but the Hi-T24 cells were 3.8-fold more haptotactic through matrigel than the Lo-T24 cells. The haptotactic activity of the Hi-T24 cells was suppressed by the addition of an anti-MMP-2 antibody, and the amounts of MMP-2 protein secreted into the spent medium by the Hi-T24 and Lo-T24 cells were 7.8+/-0.2 and 3.8+/-0.3 ng/ml (P<0.05), respectively. The quantities of tissue inhibitor of metalloproteinase-2 (TIMP-2) protein secreted by Hi-T24 and Lo-T24 cells were 133.2+/-4.3 and 168.7+/-5.6 ng/ml, respectively (P<0.05). The levels of transcription of the genes encoding MMP-2 and the transmembrane MMP, MT-MMP, evaluated by RT-PCR, were higher in the Hi-T24 cells than in the Lo-T24 cells. Expression of the TIMP-2 gene was slightly lower in the Hi-T24 cells than in the Lo-T24 cells. These results indicate that expression of the metalloproteinases are imbalanced at the gene level in human urinary bladder cancer cells at the stage of tumor progression.

Carcinoma, Transitional Cell↗

The isolation and analysis of the luminal plasma membrane of calf urinary bladder epithelium.

The luminal plasma membrane of calf urinary bladder epithelium (urothelium) has been isolated by a method designed to preserve enzymic activity as well as structural integrity. The yield was about 80 micrograms per calf bladder. Low levels of 5' nucleotidase, Mg2+-ATPase and (Na+ + K+)-ATPase activities were found in the luminal membrane fraction. Cerebroside was the major lipid present and dodecyl sulphate gel electrophoresis revealed a complex protein and glycoprotein composition in the whole membrane. A membrane fraction consisting of only the plaque areas was shown to have a simpler protein composition with major polypeptides of apparent Mr 12 000 and 22 000. These may associate to form a 30 000 apparent Mr complex which could represent the individual 'particles' of the dodecameric subunits seen by electron microscopy in the plaque regions.

Animals↗

Primary signet ring cell carcinoma of the urinary bladder. Review of the literature and report of two cases.

The signet ring cell carcinoma of the urinary bladder is a rare neoplasm; the 70 cases found in the literature pursued a fulminant and mostly fatal course; the neoplasms diffusely invaded the bladder wall without forming intraluminal growths and could not be controlled by segmental resection, radiotherapy and chemotherapy alone or in combination. We herewith present 2 cases of primary signet ring cell carcinoma of the urinary bladder--one associated with high-grade transitional cell carcinoma and in situ carcinoma--and review the literature.

Carcinoma in Situ↗

The mechanism of Na+ transport by rabbit urinary bladder.

The mechanism of Na+ transport in rabbit urinary bladder has been studied by microelectrode techniques. Of the three layers of epithelium, the apical layer contains virtually all the transepithelial resistance. There is radial cell-to-cell coupling within this layer, but there is no detectable transverse coupling between layers. Cell coupling is apparently interrupted by intracellular injection of depolarizing current. The cell interiors are electrically negative to the bathing solutions, but the apical membrane of the apical layer depolarizes with increasing Isc. Voltage scanning detects no current sinks at the cell junctions or elsewhere. The voltage-divider ratio, alpha, (ratio of resistance of apical cell membrane, Ralpha, to basolateral cell membrane, Rb) decreases from 30 to 0.5 with increasing Isc, because of the transport-related conductance pathway in the apical membrane. Changes in effective transepithelial capacitance with Isc are predicted and possibly observed. The transepithelial resistance, Rt, has been resolved into Ra, Rb, and the junctional resistance, Rj, by four different methods: cable analysis, resistance of uncoupled cells, measurements of pairs of (Rt, alpha) values in the same bladder at different transport rates, and the relation between Rt and Isc and between alpha and Isc. Rj proves to be effectively infinite (nominally 300 k omega muF) and independent of Isc, and Ra decreases from 154 to 4 omega muF with increasing Isc. In the resulting model of Na+ transport in "tight" epithelia, the apical membrane contains an amiloride-inhibited and Ca++-inhibited conductance pathway for Na+ entry; the basolateral membrane contains a Na+--K+-activated ATPase that extrudes Na+; intracellular (Na+) may exert negative feedback on apical membrane conductance; and aldosterone acts to stimulate Na+ entry at the apical membrane via the amiloride-sensitive pathway.

Animals↗

The value of transurethral sonography in tumours of the urinary bladder.

The authors report on their first experience obtained in the field of transurethral sonography in cases of tumours of the urinary bladder. Sonography is a method without complication and risks. TNM classification of urinary bladder tumours is possible. A special advantage of this method of investigation is that sonography can be performed directly before transurethral tumour resection. Moreover, during the postoperative period, sonography can be combined with any kind of control cystoscopic investigation. The determination of the depth of infiltration and extension of the tumour is a prerequisite of therapeutic procedures in cases of cancer of the bladder.

Evaluation Studies as Topic↗

A case report of inflammatory pseudosarcoma of the urinary bladder.

A case of inflammatory pseudosarcoma of the urinary bladder in a 35-year-old Japanese male is presented. This benign lesion can easily be mistaken for spindle cell sarcoma since it consists of rhabdomyoblast-like elongated strap cells showing infiltrative growth, and whether it is benign or malignant is difficult to determine by microscopic examination. In this case, spindle cell proliferation extended among bundles of the superficial muscle layer. However, no abnormal mitoses, severe nuclear atypia or cellular pleomorphism could be seen, thus indicating inflammatory pseudosarcoma. Although the lesion was not completely resected, no recurrent disease has been clinically observed for two years following transurethral resection. Urologists and surgical pathologists must be able to detect this lesion in order to avoid unnecessary surgical procedures.

Adult↗

Spontaneous rupture of the urinary bladder complicated by extensive fascitis: the importance of a high index of suspicion.

Spontaneous rupture of the urinary bladder is a rare entity. This is, in part, the cause for the low rate of correct preoperative diagnosis, the high rate of delayed diagnosis, morbidity and mortality. We report a case of spontaneous rupture of the urinary bladder in an adult patient, complicated by extensive fascitis of the abdominal wall. The stormy course and long hospitalization in the case described are characteristic of patients with spontaneous bladder rupture and warrant a high index of suspicion in order to achieve an early diagnosis.

Abdominal Muscles↗

Localization of sodium pump sites in frog urinary bladder.

[3H]Ouabain binding in frog and toad urinary bladder was investigated by short-circuit current (SCC), scintillation counting and autoradiographic techniques. SCC data and analysis of tissue digests following serosal exposure to ouabain showed that ouabain binding and inhibition of Na+ transport was completely reversible in toad bladder whereas, in frog bladder, [3H]ouabain was tightly bound and Na+ transport remained suppressed even after a 60-min washout. Mucosal exposure of frog bladder to [3H]ouabain or serosal exposure after preincubation with unlabeled ouabain led to a marked reduction in binding. Specificity of binding was assessed further by adjusting the concentration of certain (Na+ -K+)-ATPase ligands(K+, ATP) to levels known to reduce ouabain binding. High K+ concentrations and depletion of endogenous ATP by incubation under anoxic conditions resulted in a significant drop in [3H]ouabain binding. Autoradiographic analysis showed that grains are localized primarily to the basolateral plasma membranes of the granular cells, providing direct morphological evidence for the location of Na+ pumps at these sites. Although autoradiographs did not provide sufficient resolution to rule out unequivocally ouabain binding to the mitochondria-rich cell, morphological evidence suggests that grain densities are significantly higher between adjacent granular cells than between granular cell-mitochondria-rich cell interfaces.

Adenosine Triphosphatases↗

Muscarinic receptor subtypes in the submandibular gland and the urinary bladder of the rabbit: in vivo and in vitro functional comparisons of receptor antagonists.

1. In pentobarbitone-anaesthetized rabbits, the inhibitory effects of muscarinic receptor antagonists with different selectivity profiles were examined on carbachol-evoked submandibular secretion and urinary bladder contractions, and on parasympathetically nerve-evoked secretion. On isolated submandibular gland fragments, the inhibitory effects of the antagonists were studied on carbachol-evoked release of potassium and on the overflow of tritium in response to electrical field stimulation. 2. In vivo, 4-DAMP equipotently inhibited simultaneously carbachol-evoked submandibular secretory and contractile responses of the urinary bladder, while pirenzepine was found to be four times as potent in inhibiting the secretory response compared with the contractile response. 3. The inhibition of carbachol-evoked salivation caused by atropine, 4-DAMP and pirenzepine was as great as their inhibition of parasympathetic nerve-evoked salivation. Methoctramine exerted less inhibitory effect on nerve-evoked salivation than on carbachol-evoked, thus seemingly causing greater presynaptic inhibition. 4. In vitro, pirenzepine was only 30 times less potent in inhibiting carbachol-evoked potassium release than 4-DAMP (pA2, 9.58 vs 8.10). Whereas atropine, 4-DAMP and pirenzepine abolished the overflow of tritium from isolated glands in response to electrical field stimulation, methoctramine increased it. 5. It is concluded that the muscarinic secretory response in the rabbit submandibular gland is exerted via both muscarinic M1 and M3 receptors, while the contractile response of the urinary bladder to muscarinic agonists is exerted via muscarinic M3 receptors. The release of acetylcholine from nerve terminals in the gland can be inhibited via M2 autoreceptors in rabbits.

Animals↗

Enhancement by nitric oxide of neurogenic contraction in the mouse urinary bladder.

In isolated detrusor strips from the mouse urinary bladder, contractile responses to electrical field stimulation were mostly mediated by neurally released acetylcholine and ATP. The aim of this study is to investigate the possible role of nitric oxide (NO) involved in the neurogenic detrusor contraction. Repetitive electrical field stimulation evoked muscle contractions of the isolated mouse detrusor strips, which could be abolished by tetrodotoxin (TTX). NO donors including sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP) as well as exogenous NO increased, while hemoglobin and NO synthase inhibitor N(G)-nitro-L-arginine decreased the neurogenic detrusor contractions. The addition of L-arginine reversed the inhibitory effect of N(G)-nitro-L-arginine. SNP failed to affect the contractions induced by carbachol and alpha,beta-methylene ATP. These findings suggest that NO potentiated the excitatory neuromuscular transmission in electrically stimulated detrusor strips from the mouse.

Animals↗

The role of immunohistochemistry in the diagnosis of urinary bladder neoplasms.

The spectrum of neoplasms involving the urinary bladder is diverse, and, at times, different entities with distinct prognostic and managerial implications may have significant morphologic overlap. The presence of a neoplasm with an unusual morphologic appearance, such as an undifferentiated spindled, or plasmacytoid pattern may necessitate immunohistochemistry to establish the diagnosis. In this review, we discuss a series of distinct diagnostic scenarios, including high-grade undifferentiated carcinoma versus prostatic adenocarcinoma, enteric-type adenocarcinoma versus secondary colorectal adenocarcinoma, spindle cell proliferations, neoplasms with plasmacytoid morphology, endophytic tumors with a nested growth pattern, and flat urothelial lesions with atypia. We also discuss markers supporting urothelial differentiation in the context of a metastatic carcinoma from an unknown primary. The importance of using a morphologically derived differential diagnosis to guide the selection and interpretation of immunohistochemical studies is emphasized, and the varying utility (specificity) of the individual immunohistochemical markers within each setting is addressed.

Adenocarcinoma↗

Metabolic acidosis, prostaglandin E2 and insulin stimulates intracellular free calcium ([Ca2+]i) in isolated cells of toad urinary bladder.

It is well known that metabolic acidosis (MA), PGE2, and insulin stimulate H+ excretion in toad urinary bladder. In addition, PGE2 has been shown to increase in the toad bladder during MA. Our present experimental findings indicate that MA, PGE2 and insulin increase [Ca2+]i and this then may be the signal for stimulation of H+ excretion in this tissue. Isolated cells of the toad urinary bladder, obtained from toads in a chronic metabolic acidosis (MA) have a significantly higher intracellular Ca2+ ([Ca2+]i) than similar cells obtained from toads in normal acid-base balance. Prostaglandin E2 (PGE2) (10(-5) M) was found to stimulate [Ca2+]i in the same normal toad bladder cells, as determined by the fluorescence ratio technique using FURA 2/AM (P < 0.05). Insulin (100 mU/ml) was also found to stimulate [Ca2+]i in toad bladder cells (P < 0.01). The increase in [Ca2+]i following PGE2 stimulation was not dependent on extracellular Ca2+, whereas the increase seen following insulin stimulation was dependent on extracellular Ca2+.

Acidosis↗

Number, size and distribution of ganglion neurons in urinary bladder of rodents.

Whole-mount preparations of urinary bladders stained with a modified Giemsa technique were obtained from three rodent species (Guinea-pig, Calomys callosus and the C57/BLJ isogenic mouse) to identify and estimate the relative number and size of ganglionic neurons within the wall of the organ. The distribution of the ganglia was not uniform among the three species: ganglia were concentrated around the ureteral orifices in the Guinea-pig, they were scattered throughout the organ in Calomys callosus, and they were concentrated near the internal urethral orifice in the C57/BLJ mouse. In the Guinea-pig, the size of approximately 50% of the neurons lie in the range of 200 to 300 microns2. In Calomys callosus, 40% of the neurons lie in the range of 200 to 250 microns2, with 28% in the range of 50 to 100 microns2. For the C57/BLJ mouse, approximately 60% of the neurons have an area of 250 to 400 microns2.

Animals↗

Activation of K+ conductance in basolateral membrane of toad urinary bladder by oxytocin and cAMP.

We incubated toad urinary bladders with Na+-free, isotonic K+ solutions on the apical side and increased the cationic conductance of the apical membrane with nystatin (150 U/ml). Under these conditions, the short-circuit current is mostly carried by K+ flowing from mucosa to serosa. Impedance measurements showed that in nystatin-treated preparations, the electrical behavior of the tissue is dominated by the basolateral membrane properties. Oxytocin (0.1 U/ml) produced an increase of the current and the conductance of the basolateral membrane. Both the resting and the oxytocin-stimulated current were rapidly and reversibly blocked by serosal Ba2+. Addition of the adenosine 3',5'-cyclic monophosphate (cAMP) analogue [8-(4-chloropheylthio)-cAMP] to the basolateral solution mimicked the effects of oxytocin. These results show that oxytocin and cAMP stimulate a potassium conductance in the basolateral membrane and that the stimulation is not related to an increase in sodium entry through the apical membrane. Addition of ouabain (10(-3) M) to the serosal solution did not modify the stimulation by oxytocin, indicating that the activated pathway is not linked to the rate of turnover of the Na+ pump.

Animals↗

Abnormalities of responses to autonomic stimulation in the mouse urinary bladder associated with Semliki Forest virus-induced demyelination.

The responses to autonomic stimulation of the urinary bladder were studied in mice infected with Semliki Forest Virus, which has been proposed as an animal model for multiple sclerosis. Mice infected with Semliki Forest Virus showed a decreased body weight when compared with control animals, although their bladders were proportionately heavier. The pharmacological results indicated a selective change in purinergic transmission in the bladders of mice infected with Semliki Forest Virus, while cholinergic transmission remained unchanged. This was demonstrated by a significant increase in the contractile response to beta,gamma-methylene ATP accompanied by an increase in the proportion of the nerve-mediated response blocked by alpha,beta-methylene ATP. In contrast, the contractile response to acetylcholine and the atropine-sensitive component of the neurogenic response were not significantly different between the two groups of animals. Active length-tension curves were also unchanged in the mice infected with Semliki Forest Virus when compared with controls. The results are discussed in relation to those obtained from models of urinary bladder dysfunction associated with hypertrophy; whether the alteration of atropine-resistant (purinergic) function reported here is a general secondary feature of this type of bladder dysfunction or a change specific to the Semliki Forest Virus model of multiple sclerosis is not resolved. This study provides evidence that peripheral changes as well as central nervous system demyelination occur in the Semliki Forest Virus-infected mouse.

Acetylcholine↗