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Increased temperature of malignant urinary bladder tumors in vivo: the application of a new method based on a catheter technique.

PURPOSE: The aim of this study was to investigate the existence of any thermal difference between malignant tumors and inflammatory benign lesions of the human urinary bladder and to determine whether it correlates with tumor angiogenesis quantification. PATIENTS AND METHODS: A new method, developed in our institute, is introduced to detect temperature in human urinary bladder, in vivo. This method is based on a thermography catheter. We calculated the differences of the temperature of the solid tumor and of a normal area (Delta T) on 20 subjects (mean age, 72.5 years; 95% confidence interval [CI], 68.5 to 76.4). According to the biopsy histology, Eight (40%) patients had benign tumors, and 12 (60%) had malignant tumors. RESULTS: We found significant differences of Delta T between patients with benign and malignant tumor (P <.001). Also, differences were found for the mean values of angiogenesis level between malignant and benign tumors (P =.0261), and a moderated positive correlation was estimated between the degree of angiogenesis and Delta T (P =.02). Based on logistic regression analysis, we found that a 1-degree increase of Delta T triples the odds of a patient having a malignant tumor (odds ratio = 2.91; 95% CI, 1.97 to 7.78; P <.001), adjusted for the degree of angiogenesis (P =.0236) and the grade of tumor (P <.001). A threshold point of Delta T = 0.7 degrees C was determined, with sensitivity 83% and specificity 75%. CONCLUSION: These findings suggest that the calculated difference of temperature between normal tissue and neoplastic area could be a useful criterion in the diagnosis of malignancy in tumors of the human urinary bladder.

Aged↗

Absorbed dose resulting from a specially designed computed tomography technique for examination of the urinary bladder.

The absorbed spatial dose distribution resulting from a specially designed CT protocol for examination of the urinary bladder has been investigated with TLD rods in a body phantom containing tissue equivalent material. The CT examination consisted of scout view and both pre- and postcontrast scan series with 5 mm slice thickness and 5 mm unscanned intervals between successive scans. Cross-sectional dose distribution for one scan in the plane of the ovaries was measured as well as the dose profile for one scan along a line through the ovary parallel to the axis of rotation. Based on these measurements, the dose resulting from the whole CT examination was calculated, both with contiguous and noncontiguous scans. The ovarian dose was calculated for different positions of the ovaries in relation to the scanned area. The absorbed dose varied between 8.3 mGy and 9.7 mGy with the actual technique used. When contiguous scans with the same thickness were taken, the ovarian dose increased with a factor from 1.7 to 1.9. The dose resulting from the CT protocol of the urinary bladder was of the same magnitude as absorbed dose resulting from urography. When the diagnostic gain from a precise definition of tumor extent was taken into account, the dose resulting from the CT protocol was judged acceptable.

Female↗

Contribution of transurethral sonographic examination in diagnostics and treatment of superficial urinary bladder tumours.

For the determination of the operation treatment tactics concerning urinary bladder tumours, the state of the disease stage has the principal importance. Sonography introduction has reflected in more accurate diagnostics. The authors carried out the determination of the stage with the accuracy of 89.3% at 214 patients, having superficial tumours of the urinary bladder, who were treated by transurethral resection. The authors believe, that the most remarkable contribution consists in better possibility of the T2 and T3 stages differentiation.

Humans↗

[Vascularization of the posterior wall of the urinary bladder in women after past cesarean section in light of microangiographic studies].

Arterial vascularization of membranes in the urinary bladder wall has been studied in 14 women of reproductive age, who were bearing children. Four of them had exclusively spontaneous deliveries. Ten delivered at least once by cesarean section. The studies consisted in filling the uterine, ovarian and vesical arteries with Microtrast preparation. After the filling of vessels and fixation of the preparation in 10% formalin solution, specimens, 4-5 mm thick, were taken from the bladder wall at the junction with uterus, and comparatively specimens from the free parts of the uterus body. The serial specimens were used to obtain photographs by means of X-ray apparatus with microfocal tube, being implemented for structural studies. On the basis of the above-mentioned investigations we disclosed that the course of the blood vessels in membranes of the urinary bladder wall undergoes changes after routine dissection during the cesarean section. There is a disappearance of regular arrangement of the vascular network, particularly in mucous membrane. New vessels of larger calibre with an irregular course are seen to appear throughout the entire width. Such changes were not detected at sites distal to the field of operation. Specimens stemming from the urinary bladders of women, who delivered spontaneously, failed to reveal such changes.

Adult↗

Purinergic sensory neurotransmission in the urinary bladder: an in vitro study in the rat.

OBJECTIVES: To determine the response of mechanosensitive pelvic nerve afferents, arising from the rat urinary bladder, to the purinergic agonist alpha,beta-methylene ATP and to the purinergic antagonist suramin. MATERIALS AND METHODS: Using a newly developed in vitro bladder-pelvic nerve afferent model, multiunit recordings were taken from mechanosensitive pelvic nerve afferents arising from the rat urinary bladder, in response to bladder distension. Control experiments were performed by distending the bladder with saline at 0.04 mL/min, and recording the total afferent nerve activity and the bladder pressure response to the distension. Bladder distensions were then repeated using a solution of the stable purinergic agonist alpha,beta-methylene ATP (10 micromol/L), which is known to desensitize P2X-purinoceptors after prolonged exposure, and the total afferent activity and bladder pressure response were again measured. In a separate series of experiments the afferent nerve activity and bladder pressure response to bladder distension with saline was determined in the presence of the purinergic antagonist suramin (10 micromol/L) and repeated after washout of the drug. In both series of experiments, afferent nerve responses were compared with control using the paired t-test, whilst the bladder pressure responses were compared using one-way analysis of variance. RESULTS: Bladder distension with alpha,beta-methylene-ATP produced a statistically significant reduction in afferent nerve activity, by up to 75% compared with the control, whilst having no significant effect on the bladder pressure response. Bladder distension with saline in the presence of suramin (10 micromol/L) produced a significant reduction in the resultant afferent nerve activity, by 50%, which returned to normal after washout of the drug. CONCLUSION: These findings are consistent with the notion that ATP is released endogenously during bladder distension in the rat and is involved significantly in the activation of pelvic nerve afferents arising from the rat urinary bladder.

Adenosine Triphosphate↗

Blood flow of the urinary bladder: effects of outlet obstruction and correlation with bioenergetic metabolism.

This study investigated the effects of outlet obstruction on blood flow and high energy phosphates content in the rabbit urinary bladder. Mild bladder outlet obstruction was induced by placing a silicon ring (diameter 7 mm) around the bladder neck of each male New Zealand White rabbit (n = 7). Before and immediately after inducing obstruction, and 2 weeks later, the bladders were emptied and regional blood flow measured using laser Doppler flowmetry (LASERFLO BPM2, Vasamedics Inc., St. Paul, Minnesota). Six different areas of each bladder were measured, and the average blood flow calculated for each rabbit. Then, the animals were sacrificed, the bladder excised, and the tissue content of high energy phosphates determined by high performance liquid chromatography (HPLC). Six normal male New Zealand White rabbits served as controls. The results can be summarized as follows: (1) Before surgery, bladder blood flow was similar in all animals (16.3 ml/min/100 g); positioning the silicon ring around the bladder neck did not affect blood perfusion, two weeks after the induction of outlet obstruction, bladder blood flow was significantly decreased (4.9 ml/min/100 g). (2) There was no significant difference between control and obstructed bladders in NAD, AMP, or ADP content. However, the obstructed bladders contained significantly less phosphocreatine (12.0 vs 21.9 nmol/mg protein) and ATP (4.0 vs. 6.1 nmol/mg protein) than control bladders. In summary, this study showed that urinary bladder blood flow was reduced by outlet obstruction, and the reduction in blood flow was associated with decreased tissue high energy phosphates content.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

[Primary localization of malignant lymphoma in the urinary bladder?].

We report on the case of a malignant non-Hodgkin lymphoma with primary location in the urinary bladder of an 83-year-old woman. Diagnosis was established by transurethral resection of the tumor and histological examination. No clinical signs (e.g. alterations of peripheral blood count) or tumor generalization were observed. To date only 86 cases of primary localization of lymphoma in the urinary bladder have been described, whereas secondary involvement occurs in 5.4-13% of cases.

Aged↗

[Atrial natriuretic factor stimulates the frog urinary bladder osmotic permeability in presence of a cyclic nucleotide phosphodiesterase inhibitor].

The role of atrial natriuretic factor (ANF) in regulation of osmotic water permeability was studied in isolated frog Rana temporaria L. urinary bladder. It was found that ANF (rANF, 1-28) added to the serosal solution at concentrations 5 x 10(-8) M and higher dosedependently stimulated the arginine-vasotocin (AVT)-induced increase of osmotic water permeability. The effect of ANF was revealed only in presence of 3-isobuthyl-1-methylxantine (180 microM) and was accompanied by significant elevation of cGMP level in urinary bladder homogenate and isolated mucosal epithelial cells. C-ANF (des[Gln18, Ser19, Gly20, Leu21, Gly22]-ANF-(4-23)-NH2), a specific agonist of NPR-C receptor, exerted no effect on osmotic water permeability. ANF induced a significant increase of cAMP in urinary bladder homogenates (AVT, 5 x 10(-11) M: 52.3 +/- 10.6; AVT + ANF, 10(-7) M: 114.2 +/- 26.9 pmol/mg protein, n = 5, p < 0.05). The activity of adenylate cyclase in crude plasmatic membrane fraction was not changed. Milrinone, a specific inhibitor of phosphodiesterase 3, at concentrations from 25 to 80 microM, enhanced both the hydroosmotic response to AVT and AVT-stimulated cAMP production. Altogether these data demonstrate that, in the frog urinary bladder, ANF stimulates the AVT-induced increase of osmotic water permeability acting probably through NPR-A receptor-coupled mobilization of cGMP and cGMP-dependent inhibition of phosphodiesterase 3.

3',5'-Cyclic-AMP Phosphodiesterases↗

Angiography in pheochromocytoma of the urinary bladder. Report of a case.

A case of pheochromocytoma of the urinary bladder in a 20-year-old female is reported. This is the 36th reported case in the English language literature. The patient had classical symptoms of vesical pheochromocytoma with sudden onset of headache, palpitations, and blood pressure elevation during voiding. The provisional diagnosis was arrived at on clinical history, laboratory investigations, including the estimation of catecholamines and vanil mandelic acid (VMA). The diagnosis was confirmed and the tumor was exactly localized by means of angiography. The angiographic appearance of pheochromocytoma of the urinary bladder is not pathognomonic and is similar to that previously described for adrenal pheochromocytoma. Angiography is, with adequate precautions, a safe and useful procedure for ruling out synchronous adrenal or extra-adrenal tumors and for exact localization of the bladder tumor.

Adult↗

Epidermal growth factor-responsive and -refractory carcinomas initiated with N-methyl-N-nitrosourea in rat urinary bladder.

We tested the role of epidermal growth factor (EGF) in the development of low-grade superficial bladder tumors by using a heterotopically transplanted rat urinary bladder system. Weekly EGF administration (250 ng/0.5 ml of phosphate-buffered 2.1% NaCl solution) for 28 weeks into heterotopically transplanted rat urinary bladders initiated with a low dose of N-methyl-N-nitrosourea resulted in a significant increase in the incidence (17 of 25 versus 6 of 30 rats; P < 0.001) and the mean number of tumors per bladder (1.08 versus 0.20; P < 0.001) as compared with those for a vehicle-only group. Changing to vehicle without EGF for the last 8 weeks resulted in tumors in 8 of 24 rats (P = 0.02 versus the EGF group), comparable to the rate for controls. Switching from vehicle to EGF for the last 8 weeks resulted in tumors in 15 of 24 rats, comparable to the rate in the 28-week EGF group. When tumors were divided into two groups according to size (>4.2 mm3 and </= 4.2 mm3), expression of EGF receptor (EGF-R) was found in 24 of 25 "large" tumors as compared with 5 of 17 "small" tumors (P < 0.0001). The results of in situ hybridization for EGF-R correlated well with those of immunohistochemical study. These data suggest the possibility that recurrences of low-grade superficial bladder tumors are related to the continuing presence of EGF in the urine, and that blocking of EGF-R should be evaluated as a tumor inhibitor.

Animals↗

Usefulness of direct coronal CT in the diagnosis of urinary bladder tumor.

Direct coronal CT was performed on 6 cases of urinary bladder tumor in which conventional axial transverse CT failed to depict the relationship between the lesion and bladder wall. GE CT/T 8800 was used, and the bladder was scanned with patients crouched on the table opposite the gantry. The relationship between the tumor and bladder wall as well as the surrounding organs was visualized in 5 of 6 cases examined. THe CT diagnosis and histological findings coincided in 4 of these 5. Direct coronal CT was useful for diagnostic determination of clinical stage for tumors occurring in the apical or basal region of the urinary bladder.

Humans↗

Müllerianosis of the urinary bladder.

Three women, 37, 44, and 46 years of age, had masses up to 4 cm in maximal size, which involved the posterior wall of the urinary bladder, treated by transurethral resection. Microscopic examination showed prominent involvement of the lamina propria and muscularis propria by tubules and cysts lined by müllerian-type epithelium; in two cases, the latter also focally replaced the urothelium and formed polypoid projections into the bladder lumen. The tubules and cysts were usually round to oval but occasionally exhibited prominent branching. In all three cases, the glands were predominantly lined by tubal-type epithelium (including ciliated cells, intercalated, and peg cells), that represented endosalpingiosis. Each case also contained a minor component of glands lined by columnar mucinous cells (endocervicosis). In one case, there was a minor component of typical endometriosis, and, in another, endometrioid epithelium was associated with prominent pseudoxanthoma cells in the adjacent stroma. On the basis of these three cases, striking endosalpingiosis of the urinary bladder, which has not been previously documented, is usually associated with endocervicosis, endometriosis, or both, and, in such cases, the designation "müllerianosis" is appropriate. Müllerianosis can be distinguished from adenocarcinoma and various non-neoplastic glandular lesions of the urinary bladder on the basis of a variety of architectural and cytologic features.

Adult↗

Intraepithelial asymmetric-unit-membrane plaques in mammalian urinary bladder.

Asymmetric-unit-membrane (AUM) plaques are major components of the luminal surface of superficial cells in mammalian urinary bladder. We have now demonstrated ultrastructually identical AUM plaques in intraepithelial locations, at the lateral and basal surfaces of superficial cells and at the apical surfaces of intermediate epithelial cells in the urinary bladder. Typically, luminal apposing AUM plaques are present in clusters. Similar plaque clusters are present on apposing surfaces of cell pairs within the epithelium. These intraepithelial plaque clusters are in register, although often separated by a wide interspace. In areas where they come into closer apposition, they form membrane complexes resembling but distinctly different from certain types of cell-to-cell junctions. Both luminal and intraepithelial AUM plaques serve as membrane attachment sites for cytoplasmic microfilaments. Their intraepithelial location and association with microfilaments support the hypothesis that AUM plaques serve a mechanical function and modulate cell surface area during the urinary bladder distention-contraction cycle.

Animals↗

Promoting effects of unilateral ureteric ligation on two-stage urinary bladder carcinogenesis in rats.

The effect of ligation of the left ureter on the development of lesions in the urinary bladder were investigated in male F344 rats treated with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for 2 weeks followed by 0.002% N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) for 10 or 22 weeks. The lesions of the urinary bladder found in weeks 12 and 24 in rats treated with BBN and EHBN were preneoplastic papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer. The incidences and numbers of these lesions per 10 cm of basement membrane of urinary bladder were increased significantly by ureteric ligation. Treatment with BBN or EHBN only induced no remarkable change and thus the doses used were subcarcinogenic in the conditions used. The results show that unilateral ureteric ligation enhanced two-stage bladder carcinogenesis.

Animals↗

Possible rare involvement of O6-methylguanine formation as a significant mutational factor in mouse urinary bladder carcinogenesis models.

O6-methylguanine is known as one of the major premutagenic lesions in the human and rodent carcinogenesis process. O6-methylguanine-DNA methyltransferase (MGMT), which repairs methylated guanine bases, might prevent the G:C to A:T transition, and transgenic mice carrying this MGMT gene have been reported to be less sensitive to the carcinogenicity of certain alkylating agents. Here we utilized MGMT transgenic mice to assess the significance of O6-methylguanine formation during urinary bladder carcinogenesis. In experiment 1, 100 and 60 ppm N-butyl-N(4-hydroxybutyl)nitrosamine was given for 20 weeks to transgenic and non-transgenic mice in their drinking water. The incidences of urinary bladder carcinomas were not different between transgenic mice and non-transgenic mice. The mutational spectrum of the p53 gene was evaluated by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. The pattern of p53 mutations of transgenic and non-transgenic mice did not differ, and the frequencies of mutations were 40% and 42%, respectively. G:C to A:T transition mutations were particularly infrequent (1 of 14 mutations, 7%). In experiment 2, N-methyl-N-nitrosourea, which might induce O6-methylguanine in affected alleles, was given once a week, 3 times (total 5 mg) by direct instillation into the urinary bladder through an abdominal incision. No significant neoplastic lesions were detected, although the experiment was limited by severe toxicity of the treatment. p53 immunostaining was done and there was no difference in transgenic and non-transgenic mice. These results suggest that O6-methylguanine formation might not be a significant mutational factor in these mouse urinary bladder carcinogenesis models.

Adenosine Deaminase↗

Up-regulation of pituitary adenylate cyclase-activating polypeptide in urinary bladder pathways after chronic cystitis.

These studies examined changes in the expression of pituitary adenylate cyclase-activating polypeptide (PACAP) in micturition reflex pathways after chronic cystitis induced by cyclophosphamide (CYP). In control Wistar rats, PACAP immunoreactivity was expressed in fibers in the superficial dorsal horn at all segmental levels examined (L1, L2, and L4-S1). Bladder afferent cells (40-45%) in the dorsal root ganglia (DRG; L1, L2, L6, and S1) from control animals also exhibited PACAP immunoreactivity. After chronic, CYP-induced cystitis, PACAP immunoreactivity increased dramatically in spinal segments and DRG (L1, L2, L6, and S1) involved in micturition reflexes. The density of PACAP immunoreactivity was increased in the superficial laminae (I-II) of the L1, L2, L6, and S1 spinal segments. No changes in PACAP immunoreactivity were observed in the L4-L5 segments. Staining also increased dramatically in a fiber bundle extending ventrally from Lissauer's tract in lamina I along the lateral edge of the dorsal horn to the sacral parasympathetic nucleus in the L6-S1 spinal segments (lateral collateral pathway of Lissauer). After chronic cystitis, PACAP immunoreactivity in cells in the L1, L2, L6, and S1 DRG increased significantly (P </= 0.0001), and the percentage of bladder afferent cells expressing PACAP immunoreactivity also increased significantly (P </= 0.0001; 70-85%). No changes were observed in the L3-L5 DRG. These studies suggest that the neuropeptide, PACAP, may play a role in urinary bladder afferent pathways after visceral (urinary bladder) inflammation. Changes in PACAP expression after cystitis may play a role in altered visceral sensation (allodynia) and/or urinary bladder hyperreflexia in the clinical syndrome, interstitial cystitis.

Afferent Pathways↗

Pseudoneoplastic lesions of the urinary bladder and urethra: a selective review with emphasis on recent information.

Selected tumor-like lesions of the urinary bladder and urethra, particularly those that have been the subject of recent attention in the literature, are reviewed. Within the category of epithelial abnormalities, it has recently been appreciated that cystitis glandularis of the intestinal type is occasionally associated with prominent mucin extravasation into the stroma, a finding that should not lead to the misdiagnosis of adenocarcinoma. Additionally, the problems that nephrogenic adenoma may cause have been the subject of recent study, and a detailed microscopic analysis of this lesion has shed light on the relative frequency of its common, and uncommon, features. Within the category of tumor-like lesions of the bladder, the inflammatory pseudotumor has been the subject of much interest as have müllerian lesions. It has recently been appreciated that endosalpingiosis is rarely seen at this site, usually in association with endocervicosis or endometriosis, leading to the suggested usage of the designation "müllerianosis." Selected other tumor-like lesions of the urinary bladder and urethra are also reviewed, including the problems nephrogenic adenoma may cause when it involves the prostatic urethra in men or a urethral diverticulum in females as well as the peculiar stromal cells that have recently been described within some urethral caruncles.

Diagnosis, Differential↗

Enhancement by urine of urinary bladder carcinogenesis.

The role of urine as a tumor-enhancing agent in urinary bladder carcinogenesis was investigated by using the heterotopically transplanted rat urinary bladder. Bladders removed from rats initiated with the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine in drinking water for 4 or 10 weeks were heterotransplanted to syngeneic rats. These heterotopically transplanted bladders receiving repeated instillations of normal rat urine subsequent to transplantation had a higher incidence of carcinoma than did those receiving 0.9% NaCl solution. These results suggest that normal urine may contain tumor promoter(s).

Animals↗