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[A case of small cell carcinoma in the urinary bladder responding to gemcitabine/cisplatin combination therapy as neoadjuvant chemotherapy].

We report a case of primary small cell carcinoma of the urinary bladder. A 79-year-old man with the chief complaints of macrohematuria and pollakisuria was admitted to our hospital. Cystoscopy and computed tomography (CT) revealed a non-papillary broad-based bladder tumor. Histological diagnosis was small cell carcinoma of the urinary bladder, and he underwent 3 courses of neoadjuvant chemotherapy including gemcitabine and cisplatin with a preoperative diagnosis of cT3bN0M0. After the chemotherapy, cystoscopy and CT showed complete remission. Total cystectomy with ileal conduit was performed following 3 courses of chemotherapy. Microscopic examination revealed that the small cell carcinoma had disappeared and the converted squamous cell carcinoma remained only in a small part of the specimens. The patient was carefully followed for 10 months after operation, with no tumor recurrence.

Aged↗

Na transport compartment in rabbit urinary bladder.

Electron microprobe analysis was used to determine cellular electrolyte concentrations in rabbit urinary bladder. Under control conditions the mean cellular electrolyte concentrations were for Na 11.6 +/- 2.0, for K 124.1 +/- 15.3, and for Cl 26.0 +/- 5.1 mmol/kg wet weight. The dry weight content was 19.0 +/- 2.0 g/100 g. Inhibition of the Na/K-pump with ouabain resulted in drastic changes of the cellular element concentrations. Similar changes also occurred when in addition to ouabain the apical side was kept Na-free. In all epithelial layers the Na and Cl concentrations increased by 90 and 30 mmol/kg wet weight, whereas the K concentration and the dry weight content decreased by 90 mmol/kg wet weight and 6 g/100 g wet weight, respectively. With Na-free choline-Ringer's solution on the basal side ouabain led to a decrease in the K concentration by about 60 mmol/kg wet weight while the Na and Cl concentrations remained unchanged. These data indicate that the basolateral membrane is permeable to Na, choline, Cl, and K. Nystatin produced drastic changes in the cellular electrolyte concentrations when Na- or Rb-sulfate Ringer's solutions were present on the apical side. With Na-sulfate Ringer's solution the Na concentration increased by about 25, the Cl concentration by 30 mmol/kg wet weight and the dry weight content decreased by 4.5 g/100 g, respectively. With Rb-Ringer's solution about 20 mmol/kg wet weight of the cellular K was exchanged against Rb. The concentration changes were identical in all epithelial layers supporting the idea that the rabbit urinary bladder represents a functional syncytium with regard to the transepithelial Na transport.

Animals↗

Identification of GTP-binding proteins in turtle urinary bladder epithelial cells.

Water and electrolyte transport in turtle urinary bladder closely resembles that present in the mammalian collecting tubule. Although cAMP is known to participate in the control of mucosal transport processes, the GTP-binding inhibitory Gi and stimulatory Gs proteins which link receptors on the cell surface to the adenylate cyclase system remain to be identified in this urinary epithelium. To this end, individual cells harvested from the mucosal surface of the turtle bladder were isolated using a discontinuous density Ficoll gradient. Examination by electron microscopy of the material from the different layers of the Ficoll gradient confirmed that bands II and III contained carbonic anhydrase-rich cells and granular cells, respectively. Identification of Gi and Gs in carbonic anhydrase-rich and granular cells was accomplished using pertussis (PT) and cholera toxins to promote [32P] ADP ribosylation of the proteins. Separation of Gi and Gs from other cell proteins was accomplished using polyacrylamide gel electrophoresis and autoradiography. Pretreatment of cells with 0.2% triton X-100 substantially magnified the ADP-ribosylation of Gi by PT. A doublet form of Gi was present in the 40-kD region and indicated heterogeneity of the PT substrate in granular and carbonic anhydrase-rich cells. Gs was observed as a single polypeptide at the 42-kD region in both cell types. A distinct 45-kD peptide not present in mammalian collecting tubule was identified by both toxins in granular cells and by cholera toxin in carbonic anhydrase-rich cells. In summary, this investigation identified and characterized Gi and Gs proteins in carbonic anhydrase-rich and granular cells from the mucosa of turtle urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗

Age-related changes in the response of the rat urinary bladder to neurotransmitters.

The effect of age on the contractile response of the rat urinary bladder to various neurotransmitters was studied using in vitro detrusor strips isolated from female Wistar rats. The contractile responses to 8 neurotransmitters were determined for rat urinary bladders isolated from 3 age groups: 24, 16, and 6 months old. The results can be summarized as follows: 1) There was no age-dependent change in the maximum response to KCl. 2) The contractile response to norepinephrine, adenosine 5'-triphosphate (ATP), and serotonin increased with age. 3) The relaxation response to isoproterenol was significantly less in 24-month-old rats than in the other 2 age groups. 4) There were no age related changes in the responses to acetylcholine, prostaglandin F2 alpha, and angiotensin II. 5) Vasoactive intestinal polypeptide (VIP) failed to induce any response in the rat bladders of any group. 6) There were no significant differences in the ED50s for the 5 neurotransmitters among the 3 age groups. In summary, significant differences in the response to adrenergic, purinergic, and serotonergic stimulation were found as a function of age, whereas no age related changes in the response to cholinergic or generalized depolarization with KCl were found.

Aging↗

Influence of lithium pretreatment and of cooling on the responsiveness of the rat isolated jejunum and urinary bladder to muscarinic agonists.

1. The aim of the present study was to see whether contractile responses induced by muscarinic agonists in the rat jejunum and urinary bladder were differently affected by procedures that mainly influence the steps following agonist-receptor interaction. Thus, the effects of ex vivo lithium pretreatment (6.8 mmol kg-1 i.p. for 3 days) and in vitro cooling from 37 degrees C to 20 degrees C) on the contractile responses to full and partial agonists, carbachol, oxotremorine, muscarine and pilocarpine were studied. 2. Lithium pretreatment did not affect muscarinic responses on the urinary bladder. It significantly reduced responses to carbachol and oxotremorine but not to muscarine and pilocarpine on the rat jejunum. 3. A decrease of the bath temperature from 37 degrees C to 20 degrees C potentiated responses to carbachol, muscarine and oxotremorine and abolished those to pilocarpine in the urinary bladder. The same lowering of the bath temperature potentiated responses to carbachol, did not affect those to muscarine and to oxotremorine and reduced those to pilocarpine in the jejunum. 4. Together the findings indicate that differences exist in the stimulus-response coupling induced by muscarinic agonists between the two tissues and that, in a given tissue, differences exist among agonists in their ability to activate the agonist-receptor-transducer complex.

Animals↗

Lectin binding and expression of blood group-related antigens in carcinoma-in-situ and invasive carcinoma of urinary bladder.

To determine whether histochemical reactivities of carcinoma-in-situ of the urinary bladder differ from those of invasive transitional cell carcinoma, we tested a profile of eight different lectins and three antibodies directed against blood group-related antigens for 15 cases of carcinoma-in-situ and 26 cases of non-papillary (6 superficially and 20 deeply) invasive transitional cell carcinoma that had been diagnosed according to the histopathological criteria of the International Union against Cancer. For biotin-labelled lectins and monoclonal antibodies to mouse blood group-related antigens, the avidin-biotin peroxidase complex method was applied. Positive histochemical reactions of peanut agglutinin without neuraminidase treatment--PNA N(-)--in the 20 deeply invasive tumour cases were significantly higher than those in the 15 carcinoma-in-situ cases (P < 0.05). In contrast, the reactions of blood group-related antigens in the 20 deeply invasive tumour cases were significantly lower than those in the 15 carcinoma-in-situ cases or the 11 normal controls (P < 0.05). The results confirm previously reported studies of the staining of PNA N(-) and blood group-related antigens on carcinoma-in-situ and invasive tumours of urothelial organs. The application of lectins and blood group-related antigens to the histopathology of urinary bladder cancer may be helpful in the differential diagnosis of carcinoma-in-situ from invasive cancer, but neither PNA N(-) nor blood group-related antigens can be solely reliable in this.

Blood Group Antigens↗

[Small cell carcinoma of the urinary bladder: a case report].

We report a case of small cell carcinoma of the urinary bladder. A 60-year-old man with microscopic hematuria was referred to our hospital. Cystoscopy revealed a sessile tumor on the left lateral wall of the urinary bladder. The patient underwent transurethral resection of the bladder tumor (TUR-Bt). Because of muscle invasion (pT2), total cystectomy was recommended, but was not performed because the patient would not give consent for the operation. Six months after TUR-Bt, invasive bladder tumor recurred and total cystectomy was performed. Pathological examination of the operative specimen revealed small cell carcinoma. Adjuvant combined therapy of irradiation and chemotherapy (nedaplatin and etoposide) was ineffective. Metastases to retroperitoneal lymph nodes, lung and liver were detected soon after the adjuvant therapy. The patient died 15 months after his first visit to our hospital.

Carcinoma, Small Cell↗

Differential gene expression of cholinergic muscarinic receptor subtypes in male and female normal human urinary bladder.

OBJECTIVES: To study the mRNA expression of each muscarinic receptor subtype in bladder areas involved in micturition, such as the bladder dome, neck, and trigone. Our study focused on the analysis of the gene expression of muscarinic receptors in the human male and female urinary bladder. Other than the well-known role of bladder parasympathetic innervation, an extensive study of the muscarinic receptor mRNA distribution in male and female urinary bladder is still lacking. METHODS: The study was carried out on 5 female (age 56 +/- 10 years) and 5 male (age 70 +/- 9 years) patients. The patients selected for this study did not have any lower urinary tract symptoms, as determined by International Prostate Symptom Score questionnaire. The mRNAs encoding muscarinic receptor subtypes were assessed by reverse transcription-polymerase chain reaction, followed by Southern blot analysis. RESULTS: Using a molecular approach, we demonstrated the presence of all muscarinic receptor subtypes in the different urinary bladder areas involved in micturition; in particular, our data indicated that mRNAs encoding muscarinic receptors are largely expressed in all examined bladder areas, both in men and women, although with some remarkable differences and a peculiar distribution. CONCLUSIONS: Our results indicate that the pharmacology of the human bladder may be more complex than previously recognized. Furthermore, the choice to study each biopsy as a single sample and not use a pool of tissues allowed us to point out the individual variability between subjects and sex-related differences in the expression profile of muscarinic receptor subtype mRNAs.

Aged↗

Evidence for the involvement of arachidonic acid metabolites in spontaneous and drug-induced contractions of rat urinary bladder.

The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and endogenous arachidonic acid (AA) depletion on spontaneous and drug-induced contractions of the rat urinary bladder have been determined by both in vivo and in vitro experiments. Our results suggest that some AA metabolites (presumably prostaglandins) are involved in the physiologic regulation of the micturition reflex in the rat. In vivo findings indicate that the ability of various NSAIDs to inhibit distension-induced rhythmic contractions is proportional to their anti-inflammatory effectiveness. NSAIDs administration or depletion of endogenous AA at the detrusor muscle level by essential fatty acid-free diet (EFAFD) decreased the responsiveness of the urinary bladder to reflex activation. Topical AA triggered a series of neurogenic rhythmic contractions in the preparation which failed to respond to saline loading. This effect was prevented by NSAID pretreatment. The effect of topical AA was mimicked in NSAID-treated preparations by topical prostaglandins. Both NSAIDs and EFAFD reduced the responsiveness of the rat urinary bladder to acetylcholine and purinergic stimulation in vivo and in vitro. NSAIDs enhanced, while EFAFD reduced, the responsiveness of the isolated bladder to stable cholinomimetics. Responsiveness to KCl was unaffected by NSAIDs or EFAFD. These latter findings indicate that either blockade of AA metabolism along the cyclooxygenase pathway or endogenous AA depletion might alter bladder responsiveness at the postjunctional level. However, because the amplitude of distension-induced rhythmic contractions is unaffected by NSAIDs or EFAFD, it appears unlikely that endogenous prostanoids play a role in excitatory neurotransmission or in tension development during physiological-like activation of the bladder muscle. In vitro findings indicate that both NSAIDs and EFAFD reduce the myogenic contractility and the responsiveness to stretch of bladder muscle. These findings are suggestive that AA metabolites could regulate micturition by enhancing the amplitude of the myogenic contractions of the bladder muscle and, consequently, the discharge of vesical afferents to the central nervous system.

Adenosine Diphosphate↗

Peripheral blood lymphocyte subsets in urinary bladder carcinoma patients.

The percentages of pan T (CD3+), T helper (CD4+), T cytotoxic/suppressor (CD8+), B (CD22+) and natural killer (CD57+) cells in peripheral blood lymphocytes of 15 urinary bladder carcinoma patients and in parallel, 10 healthy donors were estimated, using monoclonal antibodies in indirect membrane immunofluorescence. A significant decrease in the percentage of CD3+ lymphocytes and a highly significant decrease in the proportion of CD8+ cells was revealed in urinary bladder cancer patients. This change was accompanied by a significant increase in the CD4/CD8 ratio and in the frequency of CD57+ (HNK-1+) cells. Our data document, for the first time, the complete lymphocyte profile of patients with advanced (T3) urinary bladder carcinoma. The reason and significance of the decline in CD8+ lymphocyte percentage and the increase of CD57+ cells are discussed.

Adult↗

[Grading of urinary bladder tumors by automated microscopic image analysis].

Studies were undertaken on biopsies from urinary papillomas and urothelial carcinomas of different grades (G1 to G3) along with normal urinary bladder mucosa from a total of 220 patients. They were performed by use of automated microscopic image analysis (system Robotron A 6471, software AMBA/R). As a result, the tumor grading was improved and lead to the separation of both papillomas and G1-carcinomas with high proliferative activity. In addition, it was possible to divide the G2-carcinomas into 2 groups which probably show a different biological behaviour.

Carcinoma, Transitional Cell↗

Recovery of storage and emptying functions of the urinary bladder after spinal anesthesia with lidocaine and with bupivacaine in men.

BACKGROUND: The aim of this study was to evaluate and compare the effects of spinal anesthesia with lidocaine and with bupivacaine on urinary bladder function in healthy men who were scheduled for minor orthopaedic surgical procedures. METHODS: Twenty men were randomly allocated to receive either bupivacaine or lidocaine. Before spinal anesthesia, filling cystometry was performed with the patient in the supine position and a pressure flow study was done with the patient in the standing position. After operation, cystometric measurements were continued until the patient could void urine spontaneously. The levels of analgesia and of motor blockade were recorded. RESULTS: The urge to void disappeared immediately after injection of the local anesthetics. There was no difference in the duration of lower extremity motor blockade between bupivacaine and lidocaine. Detrusor blockade lasted significantly longer in the bupivacaine group (means +/- SD, 460 +/- 60 min) than in the lidocaine group (235 +/- 30 min). Total fluid intake and urine volume accumulated during the detrusor blockade were significantly higher in the bupivacaine group than in the lidocaine group. In the bupivacaine group, the total volume of accumulated urine (875 +/- 385 ml) was also significantly higher than cystometric bladder capacity (505 +/- 120 ml) with the risk of over distension of the bladder. Spontaneous voiding of urine did not occur until segmental sensory analgesia had regressed to the third sacral segment. CONCLUSIONS: Spinal anesthesia with lidocaine and with bupivacaine causes a clinically significant disturbance of bladder function due to interruption of the micturition reflex. The urge to void disappears quickly and bladder function remains impaired until the block has regressed to the third sacral segment in all patients. With long-acting local anesthetics, the volume of accumulated urine may exceed the cystometric bladder capacity. With respect to recovery of urinary bladder function, the use of short-acting local anesthetics for spinal anesthesia seems to be preferable.

Adult↗

[Studies of the cellular immune response in patients with urinary bladder carcinoma. X. Evaluation of serum IAP and ASP levels].

Serum levels of immunosuppressive acidic protein (IAP) and acid soluble glycoprotein (ASP) were measured in 48 patients with urinary bladder carcinoma and 51 control subjects. Both IAP and ASP levels were significantly higher in the patients than in the control subjects, and the increase of these two serum substances seemed to be closely related to grading and staging of urinary bladder carcinoma. In many patients, serum IAP and ASP levels decreased after resection of tumors. There was an inverse correlation between IAP or ASP level and phytohemagglutinin (PHA)-induced lymphocyte blastogenesis (stimulation index, SI). This suggested an immunosuppressive effect of these serum factors. After chemotherapy of urinary bladder carcinoma, both IAP and ASP levels would decrease. It is suggested that serum IAP and ASP levels could be good indicators for evaluating the effect of chemotherapy.

Aged↗

Urine carcinoembryonic antigen levels are more useful than serum levels for early detection of Bilharzial and non-Bilharzial urinary bladder carcinoma: observations of 43 Egyptian cases.

BACKGROUND: Both urinary bilharziasis and urothelial neoplasia are associated with increased production of tissue carcinoembryonic antigen (CEA). PATIENTS AND METHODS: Urine and serum CEA were determined in 43 patients with urinary bladder carcinoma including 22 post bilharzial and 21 nonbiharzial cases, in addition to 10 normal control cases. RESULTS: A significant increase was detected in both urine and serum CEA levels with bladder carcinoma compared to control cases. Urinary CEA was significantly elevated in 86% of bilharzial, versus 62% in nonbilharzial bladder carcinoma. Only 10.5% of control cases had urinary CEA elevation. The mean urinary CEA in bilharzial, was higher than that of nonbilharzial carcinoma, but the difference was not statistically significant. There was a definite relationship between urine CEA and the stage of malignancy; the higher the stage, the higher the level of urine CEA. No relationship could be detected between the stage of malignancy and serum CEA, or between the grades of malignancy and urine or serum CEA levels. CONCLUSION: Urinary CEA is more useful than serum CEA in the early detection of urotherlial carcinoma particularly if provoked by bilharziasis. Its level is also correlated with the tumor stage.

Biomarkers, Tumor↗

Uracil-induced urolithiasis in the urinary bladder of rats is irritation-dependent.

The correlation between urolithiasis due to uracil administration and epithelial proliferation in the urinary bladder was investigated in male F344 rats. Animals, 6 weeks old at the start, which ingested 3% uracil alone in the diet for 4 weeks developed urolithiasis and papillomatosis of the urinary bladder, whereas addition of NaCl, particularly at high concentration (10%), to the 3% uracil in the diet blocked production of both. In contrast, NaHCO3 was without influence on either calculi or proliferative changes. These results indicate that uracil-induced epithelial proliferation is due to direct mechanical irritation by calculi, and not to any chemical stimulus presented by uracil itself.

Animals↗

Characterization of thalamic neuronal responses to urinary bladder distention, including the effect of acute spinal lesions in the rat.

UNLABELLED: Chronic visceral pain has proved to be difficult to treat. This study characterized urinary bladder distention (UBD)-evoked responses of neurons located within the ventrobasal group of the thalamus. Units were also characterized for responses to cutaneous stimuli and colorectal distention (CRD). In addition, the effects of spinal lesions on UBD-evoked responses were examined in a subset of neurons. After a stable response to UBD was established, 3 sequential lesions of the spinal cord at the mid-cervical level were performed, and responses to UBD were determined 1 and 5 minutes later. A majority of the neurons in the ventrobasal group of the thalamus were excited by UBD, demonstrated graded responses to graded distention pressures, and responded to cutaneous stimulation. No correlation between the magnitude of the responses of thalamic neurons to UBD and CRD was found. UBD-evoked thalamic neuronal activity was significantly attenuated after dorsal midline lesions of the spinal cord. The present study is a quantitative description of ventrobasal thalamic neuronal responses to UBD in the rat and provides direct neurophysiologic evidence that nociceptive information from the urinary bladder to the ventrobasal group of the thalamus ascends via a dorsal midline pathway. PERSPECTIVE: The effect of dorsal midline lesions is of profound clinical interest because it points to a potential treatment for urinary bladder pain, such as that which is characteristic of interstitial cystitis. Further research might reveal pharmacologic approaches to modulate this pain pathway and result in novel treatments for interstitial cystitis.

Afferent Pathways↗

Comparison of argyrophilic nucleolar organizer regions (AgNORs) and mitotic index in distinguishing benign from malignant canine smooth muscle tumors and in separating inflammatory hyperplasia from neoplastic lesions of the urinary bladder mucosa.

Staining for argyrophilic nucleolar organizer regions (AgNORs) has proven useful in differentiating recurrent or malignant neoplasms from less aggressive or benign ones. We applied this stain to benign and malignant smooth muscle tumors and to hyperplastic and carcinomatous lesions in the urinary bladder of dogs in an effort to determine its utility in diagnostic situations. The stain was simply performed, and the results were repeatable for different staining intervals and between staining batches. For smooth muscle tumors, enumeration of AgNORs in 100 nuclei was about as efficient as mitotic index in correctly categorizing histologically benign and malignant neoplasms. The mean number of AgNORs/100 nuclei for leiomyomas was significantly less than that obtained for leiomyosarcomas and significantly greater than that obtained for normal smooth muscle. Counts for smooth muscle tumors correlated with the mitotic indexes. Counts by an individual observer were repeated without introducing significant variation, but there was variability between observers, particularly in AgNOR counts for leiomyosarcomas. AgNORs were not useful in separating hyperplastic or polypoid cystitis from transitional cell carcinoma, misclassifying both. Mean AgNOR counts for these 2 conditions did not differ at the 5% level of significance; mitotic index was more efficient at separating the 2 conditions. There was no correlation between mitotic index and AgNOR in urinary tract mucosal specimens. This easily prepared stain may be useful in separating benign and malignant smooth muscle tumors, although AgNORs were less contributory to diagnosing mucosal lesions of the urinary bladder of dogs.

Analysis of Variance↗