Morphometry of nucleoli as an indicator for grade of malignancy of bladder tumors

To establish a new indicator for the classification of human urinary bladder cancers, the nucleoli of normal epithelial and neoplastic cells were analyzed, using morphometric techniques. By electron microscopy, the nucleolar profiles of cells from grade 2 and 3 transitional cell carcinomas were often small and irregular. Morphometry showed that the nucleolar volumes, nucleolar/nuclear volume ratios, volume densities of various nucleolar components, and the numbers of fibrillar centers (FCs) altered significantly with an increase in tumor grade. In particular, an increase in FC numbers in the nuclei of higher grade tumors was associated with a decrease in individual volume. The number of FCs in intact urothelial cells obtained from patients with bladder tumors is significantly larger than in the normal urothelial cells. This may be related to the multicentric origin of bladder cancers. These results suggest that morphometric analysis of nucleoli is useful in evaluating the degree of differentiation and invasive capacity of human bladder tumor cells. In particular, the number and individual volume of FCs may be an indicator of tumor malignancy.     

Morphometry of nucleoli as an indicator for grade of malignancy of bladder tumors

To establish a new indicator for the classification of human urinary bladder cancers, the nucleoli of normal epithelial and neoplastic cells were analyzed, using morphometric techniques. By electron microscopy, the nucleolar profiles of cells from grade 2 and 3 transitional cell carcinomas were often small and irregular. Morphometry showed that the nucleolar volumes, nucleolar/nuclear volume ratios, volume densities of various nucleolar components, and the numbers of fibrillar centers (FCs) altered significantly with an increase in tumor grade. In particular, an increase in FC numbers in the nuclei of higher grade tumors was associated with a decrease in individual volume. The number of FCs in intact urothelial cells obtained from patients with bladder tumors is significantly larger than in the normal urothelial cells. This may be related to the multicentric origin of bladder cancers. These results suggest that morphometric analysis of nucleoli is useful in evaluating the degree of differentiation and invasive capacity of human bladder tumor cells. In particular, the number and individual volume of FCs may be an indicator of tumor malignancy.     

Immunologic determination of an epidermal G2-chalone-like factor as a marker of squamous cell structures in the urinary bladder and urine in rats

The epidermal G2 chalone-like substance of the rat skin may be determined by immunochemical methods only in squamous epithelia and it is revealed neither in mucosa of the urinary bladder, nor in urine of control rats. The antigenic activity of the chalone was revealed in 37 extracts of 56 tumors of the rat bladder. All antigen-containing tumors were found to be squamous cell carcinomas, transitional cell carcinomas with squamous cell metaplasia or possessed ultramicroscopic signs of squamous cell metaplasia appearing as "pure" transitional cell carcinomas under light microscope. The epidermal G2 chalone-like substance was present in urine of 7 out of 10 rats bearing the antigen-positive tumors of the urinary bladder.     

Further testing of morphometric grading in T(A,1) urothelial carcinomas of the urinary bladder and the additional value of p53 immunoquantitation

OBJECTIVE: To analyze the value for grading of a previously developed quantitative morphometric/cytometric multivariate grading model (consisting of the mean nuclear area of the 10 largest nuclei (MNA-10, mitotic activity index = MAI and Ki-67 area% = Ki-67) in two new independent test sets of urothelial carcinomas (UCs) of the urinary bladder and to evaluate the additional value of p53 area% (p53) in this model. STUDY DESIGN: Ki-67 immunoquantitation, morphometric MAI and MNA-10 assessments using a previously described, strict protocol and matching of the resulting morphometric grade with subjective grade in two test sets of 154 T(A,1) UCs of the bladder (consensus grade between two independent observers). Further testing of this morphometric grading model was performed in 57 cases that lacked initial interobserver agreement on grade. Single and multivariate analysis of all features (including p53) was performed. RESULTS: With the previously developed morphometric/cytometric grading model, 93% (grade 1 vs. 2) and 91% (grade 2 vs. 3) of the consensus cases were correctly classified. These percentages were very similar to previous results, suggesting that the model is robust. Of the 57 cases that lacked initial interobserver agreement on grade, 53/57 (93%) were classified unambiguously as grade 1, 2 or 3 with the quantitative morphometric/ cytometric grading model. In the exploratory analysis, p53 was significant but with more overlap than the other features had. In multivariate analysis p53 did not improve the overall classification result of the original morphometric/cytometric model. CONCLUSION: The value of MNA-10, MAI and Ki-67 for grading in T(A,1) urothelial carcinomas of the urinary bladder was confirmed. p53 Did not improve overall grading classification of this combination.     

Urinary cytology for carcinoma in situ of the urinary bladder

The urinary cytologies of 14 nonpapillary carcinomas in situ of the urinary bladder were reviewed. Cytologic malignancy was often diagnosed before any clinical manifestation or cytoscopic lesion could be perceived. The cytologic characteristics of this lesion as previously described in the literature were confirmed: the background was usually clean and the tumor cells were numerous and relatively monomorphic, with many atypias. Taking into consideration the limitations discussed, urinary cytology should be regarded as having great accuracy in the early diagnosis of in situ carcinoma of the urinary bladder.     

Neo-regeneration of urinary bladder: a desired metaplasia of autologous membrane from rectosigmoid colon containing stem cells of intestinal crypts

The current management of diseases of urinary bladder requiring resection is by augmentation cystoplasty or transplantation of ureters. Transplantation of ureters is associated with morbidity and mortality. Ideal management will be by regenerating urinary bladder in vivo. Neo-regeneration of tissues and organs like abdominal wall, aponeurosis etc., has been attempted and patented. After neo-regeneration of mesoderm tissues and organs, regeneration of urinary bladder (developed from endoderm) was. In vivo surgical techniques were developed in dogs. It is known that the embryonic morphogenesis of urinary bladder is from uro-genital sinus of hind gut. A membrane, containing endoderm stem cells in crypts of recto-sigmoid colon, was surgically isolated and colonized with remnant of urinary bladder wall after extensive resection. Experimental study was performed in dogs, for 60 days to one and a half year. Regeneration of all the layers of tissues of the wall of urinary bladder was observed. The neo-regeneration phenomenon has been recognized as "desired metaplasia". The regenerated neo tissue/organ on histological examination and cystometry studies was found compatible with normal urinary bladder. The hypothesis, neo-regeneration and desired metaplasia, is discussed.     

Metatarsal metastasis from transitional cell cancer of the urinary bladder

Urinary bladder cancers can be grouped into three general categories: superficial, invasive and metastatic. Approximately 90% of malignant tumors of the urinary bladder are of epithelial origin and the majority of them are transitional cell carcinomas (TCC). Metastatic spread of urinary bladder cancers usually includes regional lymph nodes, the lung, the liver and the bones. The presence of metastasis tends to correlate with muscular wall invasion as often demonstrated at the initial diagnosis; consequently clinical bladder cancer represents a late phase of the disease. Although skeletal metastases of bladder cancers are rather common, they have been rarely described to occur in distal bones. For that reason, we report metatarsal metastasis from transitional cell cancer of the urinary bladder in a 59-year-old woman.     

FISH diagnostics

For over two decades banding has remained the "gold standard" of cytogenetic analysis, providing the first genome-wide screen for abnormalities. However, conventional cytogenetic banding techniques are limited to the detection of rearrangements involving more than 2 Mb of DNA. In addition,the identification of de novo unbalanced chromosome rearrangements provides a particular challenge for chromosome banding to decipher. In recent years a number of techniques based on FISH have evolved, all of which complement the conventional banding approaches and which have steadily increased the accuracy of cytogenetic diagnosis. FISH is now the method of choice because of the increased sensitivity, and speed with which it can be applied to a variety of cellular targets. In this article we try to highlight the technical aspects of FISH and the practical application of this technique on different tumors (soft tissue tumors, breast carcinomas, renal cell carcinomas, bladder tumors and germ cell tumors).     

What was I thinking? Eye-tracking experiments underscore the bias that architecture exerts on nuclear grading in prostate cancer

We previously reported that nuclear grade assignment of prostate carcinomas is subject to a cognitive bias induced by the tumor architecture. Here, we asked whether this bias is mediated by the non-conscious selection of nuclei that "match the expectation" induced by the inadvertent glance at the tumor architecture. 20 pathologists were asked to grade nuclei in high power fields of 20 prostate carcinomas displayed on a computer screen. Unknown to the pathologists, each carcinoma was shown twice, once before a background of a low grade, tubule-rich carcinoma and once before the background of a high grade, solid carcinoma. Eye tracking allowed to identify which nuclei the pathologists fixated during the 8 second projection period. For all 20 pathologists, nuclear grade assignment was significantly biased by tumor architecture. Pathologists tended to fixate on bigger, darker, and more irregular nuclei when those were projected before kigh grade, solid carcinomas than before low grade, tubule-rich carcinomas (and vice versa). However, the morphometric differences of the selected nuclei accounted for only 11% of the architecture-induced bias, suggesting that it can only to a small part be explained by the unconscious fixation on nuclei that "match the expectation". In conclusion, selection of ? matching nuclei ? represents an unconscious effort to vindicate the gravitation of nuclear grades towards the tumor architecture.     

Squamous and glandular differentiation in urothelial bladder carcinomas. Histopathology, histochemistry and immunohistochemical expression of carcinoembryonic antigen

This paper reports the immunochemical expression of carcinoembryonic antigen in the squamous, glandular and mixed differentiation areas observed in 190 urothelial urinary bladder carcinomas. The antigen was found to occur in 75% and 81% of all papillary and solid infiltrating carcinomas, respectively. The use of the immunohistochemical determination of CEA in improving the morphological examination of these differentiation areas and their scant presence in the prognosis of urothelial carcinomas involving squamous and/or glandular focal differentiation are discussed.     

非那雄胺联合M受体拮抗剂治疗前列腺增生合并膀胱过度活动症的疗效

目的:探讨非那雄胺联合M受体拮抗剂对前列腺增生合并膀胱过度活动症临床疗效的影响。方法:回顾性研究我院前列腺增生合并膀胱过度活动症的患者60例,随机分为实验组和对照组,每组30例。对照组患者给予M受体拮抗剂,实验组患者在对照组的基础上给予非那雄胺。观察并比较治疗前后两组患者国际前列腺症状评分(IPSS)、膀胱过度活动症评分(OABSS)、残余尿量、最大尿流率、尿急次数以及治疗期间不良反应。结果:与对照组相比,实验组患者IPSS及OABSS较低(P0.05);残余尿量较少,最大尿流率较大,尿急次数较少(P0.05);不良反应发生率较低(P0.05)。结论:非那雄胺联合M受体拮抗剂能够降低前列腺增生合并膀胱过度活动症的不良反应发生率,提高临床疗效,值得在临床上推广应用。     

On the importance of modelling organ geometry and boundary conditions for predicting three-dimensional prostate deformation

The use of an ultrasound probe or a needle guide during biopsy deforms both the rectal wall and the prostate, resulting in lesion motion. An accurate patient-specific finite element (FE)-based biomechanical model can be used to predict prostate deformations. In this study, an FE model of a prostate phantom is developed using magnetic resonance images, while soft-tissue elasticity is estimated in vivo using an ultrasound-based acoustic radiation force impulse imaging technique. This study confirms that three-dimensional FE-predicted prostate deformation is predominantly dependent on accurate modelling of prostate geometry and boundary conditions. Upon application of various compressive displacements, our results show that a linear elastic FE model can accurately predict prostate deformations. The maximum global error between FE-predicted simulations and experimental results is 0.76 mm. Moreover, the effect of including the urethra, puboprostatic ligament and urinary bladder on prostate deformations is investigated by a sensitivity study.     

The role of alpha-adrenoreceptors in the treatment of urological diseases

One of the most important clinical pharmacological invention in the last decades the role of adrenoreceptors in urological disease. The disorders of emptying the bladder are associated to the urology. Plant extracts efficacy is low, indicated only in mild symptoms, surgery has to be performed in advanced cases. Recognise, discovering the role of adrenoreceptors in the prostate, bladder neck has changed the treatment of benign prostatic hyperplasia. Relieving the muscle tension leads to a better urinary flow, decreased residual urine and less complaints. Combination with 5alpha-reductase inhibitor a better results can be achieved. The inflammation in prostate is a frequent disease of all age of males. Spasm of the bladder neck maintains the complaints additional alpha-blocker treatment combined with antibiotics, anti-inflammatory drugs are the best choice to cure the patients. Alpha-adrenergic receptor can be found in the lower part of ureter as well. To promote the spontaneous expulsion of lower ureter stones, or fragments after ESWL (extracorporal shock wave lithotripsy) the alpha-blockers are highly recommended.     

Evaluation of human bladder tumors by ultrastructural morphometric techniques

To estimate the malignancy of the human urinary bladder tumors, various cellular components of normal and neoplastic bladder epithelial cells were examined using morphometric techniques at the electron microscopic level. Nuclear to cytoplasmic ratios were found to be 1:5 in normal epithelial cells, 1:4 in superficial grade 1 (G1) tumor cells, 1:3 in superficial grade 2 (G2) tumor cells and 1:2 in invasive grade 3 (G3) tumor cells. Nuclear volumes were largest in G3 tumor cells, but no differences were seen in cell volumes between normal epithelial and tumor cells. The volumes and surface areas of the rough-surfaced endoplasmic reticulum (rER) and lysosomes per cell decreased progressively from G1 to G3 tumor cells. The volume density of tonofilaments was increased in G1, but decreased in G2 and G3 tumor cells. The cisternal thickness of the rER and Golgi complex was also increased in G1 tumor cells. From these results, it was concluded that morphometric analysis may be useful in evaluating the degree of differentiation and invasive potential of human bladder tumor cells in the low and intermediate risk groups.     

A comparative study in morphometric grading of transitional cell carcinoma of the urinary bladder

To overcome the considerable observer inconsistency in the histologic grading of transitional cell carcinomas, the value of four different morphometric grading methods was investigated in 61 tumors of the bladder. Only two methods showed satisfactory reproducibility. Both methods, one based on random nuclear sampling and the other on selective nuclear sampling, showed an increase in the mean and standard deviation of the nuclear area with higher tumor grades (P less than .00001). Morphometric classification of the learning set (44 cases) was in agreement with the unequivocally assessed histologic grade in 35 cases (79.5%) using random sampling and in 38 cases (86.4%) using selective sampling. By reducing the grading classes to "low" (grades 1 and 2) and "high" (grade 3) and by introducing a classification probability threshold (0.80), an accurate morphometric classification was achieved in 38 cases (86.4%) using random sampling and in 41 cases (93.2%) using selective sampling. Of the 17 cases with histologic grading discrepancies, all 10 low-grade tumors (with discrepancies of grade 1 versus grade 2) were correctly classified as low-grade carcinomas by both of the morphometric methods; in the remaining 7 cases, with low-versus-high discrepancies (grade 2 versus grade 3), the selective method yielded better correlation with the tumor stage and clinical follow-up. It is concluded that morphometric classification is an acceptable alternative for histologic grading by pathologists, provided that the reproducibility of the method is confirmed. Although both random and selective sampling yielded satisfactory classifications, the selective method gave more reliable results as confirmed by the clinical behavior.     

Medical therapy for benign prostatic hyperplasia: new terminology, new concepts, better choices

This article discusses 3 areas of medical therapy for benign prostatic hyperplasia (BPH) that are undergoing extensive research and evaluation: 1) the use of muscarinic receptor antagonists to treat lower urinary tract symptoms (LUTS) in men with BPH; 2) the definition of an "enlarged prostate"; and 3) sexual function and LUTS. Fears of worsening obstructive symptoms or causing acute urinary retention often keep practitioners from prescribing muscarinic receptor antagonists to men who might have concomitant bladder outlet obstruction; a multicenter, multinational, double-blind study showed that tolterodine is safe for men with low postvoid residual volumes. Most urologists accept that a prostate volume of more than 40 mL is consistent with an enlarged prostate; there is more debate regarding prostate volumes of 30 to 40 mL. Recently presented data suggest that combination medical therapy might be effective for men having prostates with volumes of more than 25 mL. The association between voiding and sexual function has been increasingly recognized and investigated, and there seem to be common pathophysiologic mechanisms governing both conditions. Targeted treatment algorithms addressing both conditions seem warranted.     

Suppression of the PI3K Pathway In Vivo Reduces Cystitis-Induced Bladder Hypertrophy and Restores Bladder Capacity Examined by Magnetic Resonance Imaging

This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL)-1α, IL-6 and tumor necrosis factor (TNF)α levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.     

Effect of bombesin, bradykinin, substance P and CGRP in prostate, bladder body and neck.

Lower urinary tract tissues respond heterogeneously to adrenergic and cholinergic agents. However, the action of bioactive peptides on these tissues has not been extensively studied. The contractile and relaxant effects of nine peptides-bradykinin, cholecystokinin, vasoactive intestinal polypeptide, gastrin, substance P, bombesin, neuropeptide Y, calcitonin gene-related peptide, and motilin-have been compared in the rat bladder body, bladder neck, and left ventral prostate in vitro. All three tissues contracted to bombesin and to bradykinin, although the bladder neck was less sensitive to the contractile effects of bradykinin than the other two tissues. Substance P only contracted the bladder body. Of all the peptides tested, relaxation was only observed to calcitonin gene-related peptide, which relaxed the bladder neck and prostate (phenylephrine-contracted) but not the bladder body (carbamylcholine-contracted). Thus lower urinary tract tissues are responsive to certain bioactive peptides in a nonhomogeneous fashion. These studies raise the possibility that selective modulation of peptide function may be an approach to therapy of urogenital disorders.     

Possible involvement of O6-methylguanine formation and p53 dysfunction in mouse urinary bladder carcinogenesis

The significance of O6-methylguanine formation in urinary bladder carcinogenesis was examined using O6-methylguanine-DNA methyltransferase (MGMT) transgenic mice carrying the ada gene. The ada MGMT transgenic mice demonstrated no differences in development of carcinogens-induced urinary bladder carcinomas compared with non-transgenic mice. Furthermore, no variation in p53 mutation frequency was evident between the two groups. The results indicated that other repair systems may have an important role for urinary bladder carcinogenesis. p53 knockout mice showed high sensitivity to urinary bladder carcinogens and increased cell proliferation plays an important role in urinary bladder carcinogenicity of p53 knockout mice. In addition, p53 knockout mice have an organ-specific increased sensitivity to carcinogenicity.     

Bladder Leiomyoma Presenting With LUTS and Coexisting Bladder and Uterine Leiomyomata: A Review of Two Cases

Mesenchymal tumors of the urinary bladder are a rare occurrence, the most common among them being leiomyoma of the bladder. These tumors commonly present with irritative urinary symptoms progressing gradually to obstructive symptoms as the size increases. We report on two patients who presented with lower urinary tract symptoms (LUTS). One of the patients also had concomitant bladder and uterine leiomyomata, which is the first such case to be reported in the literature. It is essential to differentiate leiomyoma from other common causes of LUTS. Cold cup biopsy has a significant false-negative rate and, in such cases, a wide local excision provides an optimal cure with excellent results.Key words: Bladder leiomyoma, Uterine fibroid, Lower urinary tract symptomsBenign tumors of the urinary bladder are rare and can present with a wide spectrum of complaints ranging from irritative to obstructive urinary symptoms.¹ Here we report on two patients who presented with lower urinary tract symptoms (LUTS), one of whom also had concomitant multiple uterine fibroids. To our knowledge, this is the first case to be reported in the literature.