Bladder Tumours (bladder + tumour)

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Medical Sciences100%

Selected Abstracts

TRANSURETHRAL RESECTION OF BLADDER TUMOURS

BJU INTERNATIONAL, Issue 8 2010
Erik B. Cornel
No abstract is available for this article. [source]

Idiopathic myelofibrosis with extramedullary haemopoiesis involving the urinary bladder in a Chinese lady

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2002
Y. K. MAK
Extramedullary haemopoiesis (EMH) associated with idiopathic myelofibrosis most commonly involves the reticuloendothelial organs, such as the spleen and liver, although ectopic haemopoietic tissue has also been described rarely in the lymph nodes, skin, gastrointestinal tract, pleura, peritoneum, central nervous system, and genital and urinary tracts. We report on a 54-year-old Chinese lady with a long history of idiopathic myelofibrosis who presented with gross haematuria and left hydronephrosis due to EMH in the bladder trigone. Cystoscopic examination revealed a sessile necrotic papillary growth at the trigone, obstructing the left ureteric orifice. Transurethral resection of the bladder tumour was performed, and microscopic examination of the tumour chips demonstrated atypical megakaryocytes, immature granulocytes and normoblasts, confirming the presence of EMH. The residual bladder tumour responded well to low dose radiotherapy, with subsequent disappearance of haematuria and normalization of ultrasonogram findings. [source]

Glycinothorax: a new complication of transurethral surgery

ANAESTHESIA, Issue 2 2000
J. A. L. Pittman
A 76-year-old woman sustained inadvertent perforation of her posterior bladder wall during transurethral resection of a bladder tumour. In the immediate postoperative period, she developed life-threatening respiratory failure following the formation of a large, unilateral pleural effusion. After therapeutic drainage, biochemical analysis of the effusion revealed that it had a high concentration of glycine. The fluid used for intra- and postoperative bladder irrigation had leaked from the perforated bladder and collected in the pleural cavity. This type of hydrothorax complicating endoscopic urological surgery has not been described previously. [source]

Immediate administration of intravesical mitomycin C after tumour resection for superficial bladder cancer

BJU INTERNATIONAL, Issue 3 2006
A. HUGH MOSTAFID
OBJECTIVE To assess the feasibility and safety of administering intravesical mitomycin C in theatre immediately after transurethral resection of bladder tumour (TURBT). PATIENTS AND METHODS A protocol was developed to allow the safe administration of mitomycin C in theatre immediately after TURBT. Over a 32-month period all patients not excluded by the protocol were given mitomycin C in theatre after TURBT, and any adverse events reported. RESULTS In all, 177 instillations were carried out; there were two minor patient-related complications, and no staff-related adverse events. CONCLUSION The immediate administration of mitomycin C in theatre after TURBT is feasible and safe for patients and staff. It provides the earliest and surest prophylaxis against tumour cell re-implantation at TURBT. [source]

Alterations in connexin expression in the bladder of patients with urge symptoms

BJU INTERNATIONAL, Issue 4 2005
Jochen Neuhaus
OBJECTIVE To compare the formation of gap junctions between detrusor smooth muscle cells in situ and the distribution of connexin (Cx)40, Cx43 and Cx45 expressions in bladder biopsies from a control group (with bladder tumour) and from patients with urge symptoms, as smooth muscle cells of the human detrusor muscle communicate via gap junctions and express several connexin subtypes, alterations of which may be involved in the causes of lower urinary tract symptoms. MATERIALS AND METHODS Connexin expression is prominent in myofibroblast-like cells, supposedly involved in afferent signalling pathways of the bladder. Their strategic position directly beneath the urothelium suggests they are a link between urothelial ATP signalling during bladder filling and afferent A,-fibre stimulation for co-ordination of bladder tonus and initialization of the micturition reflex. Modification of their coupling characteristics may have profound impact on bladder sensation. Bladder tissue probes of patients undergoing cystectomy or transurethral tumour resection for bladder cancer were used as controls. Tissue samples from patients with severe idiopathic urge symptoms were taken for exclusion diagnostics of interstitial cystitis (IC) and carcinoma in situ. The formation of functional syncytia between detrusor smooth muscle cells were examined in dye-coupling experiments by injecting with Lucifer Yellow. The morphology and structure of gap junctions were assessed by transmission electron microscopy and immunogold labelling of Cx43 and Cx45. The expression of connexin subtypes Cx40, Cx43 and Cx45 was compared by indirect immunofluorescence, and confocal laser scanning microscopy used for semiquantitative analysis. RESULTS There was dye coupling between smooth muscle cells of the detrusor in situ. Electron microscopy and immunogold labelling showed very small gap junctional plaques. These findings were confirmed by confocal immunofluorescence. Semiquantitative analyses showed significantly higher Cx43 expression in the detrusor muscle, and a tendency to higher Cx45 expression in the suburothelial layer associated with urge symptoms, whereas Cx40 expression was unaffected. CONCLUSIONS Smooth muscle cells of the human detrusor muscle are coupled by classical gap junctions, forming limited local functional syncytia. Both Cx43 and Cx45 are expressed at low levels in normal detrusor. Up-regulation of Cx43 in patients with urge incontinence supports the possibility of functional changes in the syncytial properties of detrusor smooth muscle cells in this condition. In addition, the observed increase of Cx45 in the myofibroblast cell layer supports the idea that alterations in sensory signalling are also involved. Comparison with previous reports implies that the pathophysiology of urgency is distinct from that of the unstable bladder and other forms of incontinence. [source]

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma

BJU INTERNATIONAL, Issue 4 2005
Elli Ioachim
OBJECTIVE To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. MATERIALS AND METHODS Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27,89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. RESULTS Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. CONCLUSION Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression. [source]

Superficial bladder tumours: analysis of prognostic factors and construction of a predictive index

BJU INTERNATIONAL, Issue 4 2003
B. Ali-El-Dein
OBJECTIVES To assess the prognostic factors that could be used to predict tumour recurrence and progression, and to construct and validate a predictive index. PATIENTS AND METHODS Between June 1991 and December 2000, 533 patients (418 men and 115 women; mean age 55.4 years) underwent complete transurethral resection of histologically confirmed pTa and pT1 transitional cell carcinoma of the bladder, after which 377 (test series) were randomized into two subsequent studies, of six groups, to receive adjuvant intravesical sequential bacillus Calmette-Guérin (BCG) and epirubicin, BCG alone, epirubicin (50 or 80 mg), adriamycin 50 mg or no adjuvant therapy. Factors potentially affecting tumour recurrence or progression were assessed using univariate and multivariate analysis, i.e. tumour stage, histological grade, DNA ploidy, history of recurrence, multiplicity, size, tumour configuration, associated carcinoma in situ, recurrence at the first 3-month check cystoscopy and the use of adjuvant therapy. The regression coefficients determined by Cox regression analysis were used to construct a predictive index (PI). The algebraic sum of the regression coefficients of the factors with independent and significant association with disease-free survival for each case represented a proportional hazard score (PHS). The PI was validated in another series of 156 patients (validation series) in whom the same regression coefficients for the same significant factors as the test series were used to categorize it into three risk groups. Kaplan-Meier survival curves were plotted to compare the different risk categories in both test and validation series. RESULTS The mean (sd, range) follow-up in the test and validation series were 58 (19, 5,96) and 28.3 (14.9, 2,94) months, respectively. In the test series, tumour stage, DNA ploidy, multiplicity, history of recurrence, tumour configuration, cystoscopy result and the type of adjuvant therapy had independent significance for recurrence on multivariate analysis. For progression, the cystoscopy result, DNA ploidy and grade were the only independent and significant predictors. The ranges of PHS for the factors affecting recurrence-free and progression-free survival were 0.0,7.14 and 0.0,5.84, respectively, which were divided equally into three risk categories with significant differences on Kaplan-Meier curves and a log-rank test (P < 0.001). The three categories in the validation series were significantly different from each other and each was comparable with that in the test series. CONCLUSIONS Tumour stage, DNA ploidy, multiplicity, history of recurrence, tumour configuration and type of adjuvant therapy affected independently the rate of recurrence after resecting superficial bladder tumour. Recurrence at the 3-month cystoscopy, histological grade and DNA ploidy were the only predictors of progression to muscle-invasion. The PI dividing the patients into three risk groups with different treatment and follow-up strategies for recurrence and progression was reproducible in a validation series. [source]

Recurrence and progression in stage t1g3 bladder tumour with intravesical bacillus calmette-guérin (Danish 1331 strain)

BJU INTERNATIONAL, Issue 3 2003
FRCS(Urol), M.M. Kirollos
No abstract is available for this article. [source]

Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette-Guérin (Danish 1331 strain)

BJU INTERNATIONAL, Issue 6 2002
J.N. Kulkarni
Objective ,To report recurrence and progression rates in patients with T1G3 superficial bladder carcinoma treated with intravesical bacille Calmette-Guérin (BCG, Danish 1331 strain) after complete transurethral resection. Patients and methods ,Data from the records of 111 patients with T1G3 bladder carcinoma treated between January 1991 and December 1999 were analysed for recurrence, progression, salvage therapy and survival. Results ,Of the 111 patients with T1G3 bladder tumours, 69 had intravesical BCG therapy, 20 radical cystectomy and 22 only transurethral resection (TUR). Of the 69 patients receiving BCG therapy 37 (54%) had no recurrence, and 24 (35%) had a recurrence that was not muscle-invasive (Ta/T1) and were treated with TUR only. The remaining eight (12%) progressed to muscle invasion and had salvage cystectomy. During the follow-up six patients died, four from disease and three from other causes, while the remaining 63 are alive and well. Of the other 42 patients, 15 are alive after radical cystectomy and 18 after TUR. Conclusion ,This series further confirms the benefits of intravesical BCG (Danish 1331) in an adjuvant setting; furthermore, this treatment facilitates bladder preservation by reducing recurrences and delaying the progression in many patients. [source]

Is microscopic haematuria a urological emergency?

BJU INTERNATIONAL, Issue 4 2002
M.A. Khan
Objective ,To determine the prevalence of urological pathology in a retrospective and prospective study of patients with microscopic haematuria attending a haematuria clinic. Patients and methods ,Between January 1998 and May 2001, 781 patients attended the haematuria clinic; of these, 368 (47%; median age 60 years, range 18,90) had a history of microscopic haematuria, as detected by urine dipstick testing. These patients were investigated by urine culture and cytology, renal ultrasonography, intravenous urography (IVU), flexible cystoscopy, urea and electrolyte analysis, and assay of prostate specific antigen (PSA) where appropriate. Results ,Urine cytology showed no malignant cells in any patient with a history of microscopic haematuria. In 143 patients (39%), urine cytology showed no red blood cells and all other investigations were normal. Of the remaining 225 patients, IVU showed a tumour in one (bladder), renal stones in 15 and an enlarged prostate in two. Renal ultrasonography detected no additional pathology. Urine analysis showed one urinary tract infection. Flexible cystoscopy detected five patients with a bladder tumour (all G1pTa), two urethral strictures, five bladder stones and enlarged prostates, six enlarged prostates only, and nine red patches in the bladder, showing one patient with carcinoma in situ . No PSA levels were suggestive of prostate cancer. Conclusion ,Patients with dipstick-positive haematuria should be re-assessed by urine microscopy before referral. As only 1.4% of patients had a malignant pathology (all noninvasive), microscopic haematuria should be regarded as a separate entity from macroscopic haematuria, and such patients do not need to be referred urgently. [source]

MAGE-A9 mRNA and protein expression in bladder cancer

INTERNATIONAL JOURNAL OF CANCER, Issue 10 2007
Valérie Picard
Abstract In a previous analysis, we showed that MAGE-As were the most frequently expressed cancer-testis antigens in human bladder tumours. Here, we further characterized by RT-PCR the expression of this family of genes by analyzing specifically MAGE-A3, -A4, -A8 and -A9 mRNAs in 46 bladder tumours and 10 normal urothelia. We found that they were expressed in 30, 33, 56 and 54% of tumours, respectively. Although MAGE-A8 was the most frequent, its expression was low and was also found in most normal urothelia. The other MAGE-A mRNAs were all tumour-specific but MAGE-A9 mRNA was expressed at a higher level and was two times more frequent in superficial than in invasive tumours. To study the expression of the protein, we produced 2 MAGE-A9-specific monoclonal antibodies (mAbs) presenting no cross-reactivity with other MAGE-A proteins. MAb 14A11, was used to analyse the expression of the antigen in testis and tumour samples by immunohistochemistry. In testis, MAGE-A9 expression was restricted to primary spermatocytes. Most bladder tumours that expressed the MAGE-A9 transcript were positive with mAb 14A11. Staining was heterogeneous but half of the tumours showed over 75% positive cells. Finally, we showed that treatment of bladder cancer cells with the methylation inhibitor, 5-aza-2,-deoxycytidine, alone or in combination with the histone deacetylase inhibitors MS-275 and 4-phenylbutyrate could strongly induce the expression of MAGE-A9. These results show that MAGE-A9 is frequently expressed in superficial bladder cancer and could be a relevant target for immunotherapy or chemoimmunotherapy because its expression can be induced by chemotherapeutic drugs. © 2007 Wiley-Liss, Inc. [source]

Chromosome 9 deletions are more frequent than FGFR3 mutations in flat urothelial hyperplasias of the bladder

INTERNATIONAL JOURNAL OF CANCER, Issue 5 2006
Johanna M.M. van Oers
Abstract Flat urothelial hyperplasias (FUHs) in patients with papillary bladder tumours frequently show deletions of chromosome 9, suggesting that FUH could be the first neoplastic step in the development of papillary bladder cancer. FGFR3 mutations are frequent in non-invasive papillary tumours with low risk of progression. Our aim was to investigate the frequency of FGFR3 mutations and deletions of chromosomes 9p/q and 8p/q in FUH. Thirty FUH and 9 simultaneous or consecutive tumours were detected by 5-ALA-based photodynamic cystoscopy. DNA was isolated from frozen sections and whole genome amplification was done by I-PEP-PCR, followed by LOH analysis on chromosomes 8p/q and 9p/q. FGFR3 mutations were detected by SNaPshot analysis. LOH analysis on FUH revealed deletions at 9p/q (11/30, 37%) and 8p/q (3/30, 10%). FGFR3 mutations were found in 7/30 FUH (23%). Only 2 FUH showed an FGFR3 mutation without deletions of chromosome 9. In contrast, 6 FUH revealed chromosome 9 deletions but wild type FGFR3 (p = 0.03). These results suggest that chromosome 9 deletions are the earliest genetic alterations in bladder cancer. The detection of FGFR3 mutations in FUH further supports the role of this lesion as precursor of papillary bladder cancer. © 2006 Wiley-Liss, Inc. [source]

Nurse-led flexible cystoscopy: the UK experience informs a New Zealand nurse specialist's training

INTERNATIONAL JOURNAL OF UROLOGICAL NURSING, Issue 2 2007
Sue Osborne
Abstract Flexible cystoscopy utilizes a fibre-optic scope with a light source to examine the internal surfaces of the bladder and urethra. The procedure is undertaken to investigate and diagnose the cause of lower urinary tract symptoms. It is also used extensively to detect the recurrence of bladder tumours in people diagnosed with transitional cell carcinoma of the bladder and kidney. In the UK, the advent of flexible cystoscopy clinics undertaken by appropriately trained and supervised nurses has been one way of improving provision of a flexible cystoscopy service. Information from published literature informed the decision to establish a nurse-led flexible cystoscopy clinic at one large District Health Board in New Zealand. This article reviews the current body of knowledge on nurse-led flexible cystoscopy, focusing on the education and training required to prepare nurses for independent cystoscopy practice. Literature findings are discussed, along with the observations of a urology nurse specialist undertaking flexible cystoscopy training in New Zealand and anecdotal evidence from visits with nurse cystoscopists in England during 2006. Carefully designed research studies published in literature have a key role to play in augmenting the body of evidence around this relatively new area of nursing practice, and as such should be strongly encouraged in both countries. It is recommended that nurse cystoscopy training and competencies are standardized and adopted internationally in order to increase the transferability of findings from research on the clinical outcomes of nurses performing nurse-led flexible cystoscopy. [source]

Absence of FGFR3 mutations in urinary bladder tumours of rats and mice treated with N -butyl- N -(-4-hydroxybutyl)nitrosamine

MOLECULAR CARCINOGENESIS, Issue 3 2005
Claire Dunois-Lardé
Abstract Frequent activating mutations of FGFR3 (fibroblast growth factor receptor 3) are found in human urothelial cell carcinomas, particularly in superficial papillary tumours (in 74%,84% of pTaG1-G2), but not in carcinomas in situ (CIS) and at a low rate in invasive tumours (in 16%,21% of pT1-4). In mice and rats, BBN (N -butyl- N -(4-hydroxybutyl)nitrosamine) specifically induces bladder tumours. In rats, superficial papillary tumours are mostly observed. In mice, tumour progression follows the CIS pathway: CIS are first observed, followed by tumours that invade surrounding muscle. Therefore, we looked for FGFR3 mutations in these two animal models of bladder cancer. Only the FGFR3b isoform is expressed in human urothelium and derived tumours. We identified the FGFR3b isoform in rats for the first time and showed that this is the main isoform expressed in the bladder urothelium and derived carcinomas in mice and rats, as in humans. SSCP and sequence analysis of FGFR3b showed sequence changes (polymorphisms or silent mutations) in four BBN-induced rat and mouse bladder tumours. The absence of activating mutations of FGFR3 in the mouse model was in agreement with the fact that mouse BBN-induced bladder tumour progression mimics the CIS pathway. The absence of FGFR3 mutations in the rat bladder tumours suggests that, at least at the genetic level, rat superficial papillary tumours differ from their human counterparts. © 2005 Wiley-Liss, Inc. [source]

Discovery of myopodin methylation in bladder cancer,

THE JOURNAL OF PATHOLOGY, Issue 1 2008
V Cebrian
Abstract Myopodin is an actin-binding protein that shuttles between the nucleus and the cytoplasm. After identifying an enriched CpG island encompassing the transcription site of myopodin, we aimed at evaluating the potential relevance of myopodin methylation in bladder cancer. The epigenetic silencing of myopodin by hypermethylation was tested in bladder cancer cells (n = 12) before and after azacytidine treatment. Myopodin hypermethylation was associated with gene expression, being increased in vitro by this demethylating agent. The methylation status of myopodin promoter was then evaluated by methylation-specific polymerase chain reaction (MS-PCR) analyses. Myopodin was revealed to be frequently methylated in a large series of 466 bladder tumours (68.7%). Myopodin methylation was significantly associated with tumour stage (p < 0.0005) and tumour grade (p = 0.037). Myopodin expression patterns were analysed by immunohistochemistry on tissue arrays containing bladder tumours for which myopodin methylation was assessed (n = 177). The presence of low nuclear myopodin expression alone (p = 0.031) or combined with myopodin methylation (p = 0.008) was associated with poor survival. Moreover, myopodin methylation in 164 urinary specimens distinguished patients with bladder cancer from controls with a sensitivity of 65.0%, a specificity of 79.8%, and a global accuracy of 75.3%. Thus, myopodin was identified to be epigenetically modified in bladder cancer. The association of myopodin methylation and nuclear expression patterns with cancer progression and clinical outcome, together with its ability to detect bladder cancer patients using urinary specimens, suggests the utility of incorporating myopodin methylation assessment in the clinical management of patients affected by uroepithelial neoplasias. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

A comparison of white-light cystoscopy and narrow-band imaging cystoscopy to detect bladder tumour recurrences

BJU INTERNATIONAL, Issue 9 2008
Harry W. Herr
OBJECTIVE To determine whether narrow-band imaging (NBI) cystoscopy enhances the detection of non-muscle-invasive bladder tumours over standard white-light imaging (WLI) cystoscopy, as surveillance WLI is the standard method used to diagnose patients with recurrent bladder tumours, but they can be missed by WLI cystoscopy, possibly accounting for early recurrences. PATIENTS AND METHODS We evaluated 427 patients for recurrent bladder tumours by WLI cystoscopy, followed by NBI cystoscopy as a further procedure, using the same video-cystoscope. Recurrent tumours visualized by WLI or NBI cystoscopy were mapped, imaged, biopsied and subsequently treated by transurethral resection (TUR) or fulguration. Biopsies or TUR specimens obtained by WLI and NBI were examined separately for presence of tumour. RESULTS In all, 103 patients (24%) had tumour recurrences; 90 (87%) were detected by both WLI and NBI and another 13 (100%) only by NBI cystoscopy. NBI detected extra papillary tumours or more extensive carcinoma in situ in 58 (56%) patients found to have recurrences. The mean number of recurrent tumours visualized on WLI cystoscopy was 2.3, vs to 3.4 seen on NBI cystoscopy (P = 0.01). CONCLUSION NBI cystoscopy improved the detection of recurrent non-muscle-invasive bladder tumours over standard WLI cystoscopy. [source]

Association of vitamin-D receptor (Fok-I) gene polymorphism with bladder cancer in an Indian population

BJU INTERNATIONAL, Issue 4 2007
Rama D. Mittal
OBJECTIVE To explore the association of vitamin-D receptor (VDR) genotypes and haplotypes (variants at the Fok-I, and Taq-I sites) with the risk of bladder cancer, as vitamin D is antiproliferative and reported to induce apoptosis in human bladder tumour cells in vitro. PATIENTS, SUBJECTS AND METHODS A case-control study using polymerase chain reaction-restriction fragment length polymorphism was conducted in 130 patients with bladder cancer and 346 normal healthy individuals in a north Indian population. Patients were also categorized according to grade and stage of tumour. RESULTS There was a significant difference in genotype and allelic distribution of VDR (Fok-I) polymorphism in the patients (P = 0.033 and = 0.017, respectively). The FF genotype was associated with twice the risk for bladder cancer (odds ratio 2.042, 95% confidence interval, CI, 0.803,5.193). There was no significant difference in genotypic distribution or allelic frequencies of the VDR (Taq-I) polymorphism (P = 0.477 and 0.230) when compared with the controls. The stage and grade of the bladder tumours had no association with VDR (Fok-I and Taq-I) genotypes. There was a significant difference in the frequency distribution of the haplotypes FT and fT (P < 0.001); these haplotypes had a protective effect in the control group (odds ratio 0.167, 95% CI 0.096,0.291, and 0.079, 0.038,0.164). CONCLUSION These data suggest that VDR (Fok-I) polymorphism is associated with the risk of bladder cancer. Further, the results for the haplotype FT and fT indicate that patients with this haplotype have a lower risk of developing bladder cancer than those with other haplotypes. [source]

Superficial papillary urothelial carcinomas in young and elderly patients: a comparative study

BJU INTERNATIONAL, Issue 3 2004
Mario Migaldi
OBJECTIVE To compare the clinicopathological and immunohistochemical findings of superficial papillary transitional cell carcinomas in ,young' and ,elderly' patients, as the natural history and prognosis of bladder tumours in young patients remains a matter of debate. PATIENTS AND METHODS Tumours from 50 patients with superficial urothelial tumours of the bladder diagnosed before 45 years old (,young' group, follow-up 25,119 months) were compared with 90 similar tumours developed in patients aged >55 years (,elderly', follow-up 24,102 months). All the patients had a transurethral resection with curative intent, and none had received any therapy before surgery. After surgery only patients diagnosed with pT1 tumours were treated by intravesical bacille Calmette-Guérin (BCG) instillations; all received intravesical BCG if there was a recurrence. The clinicopathological variables, recurrence and disease-free interval to recurrence were assessed. Proliferative activity (MIB-1) and expression of cell-cycle regulation proteins cyclin D1, p53 and p27kip1 were detected by immunohistochemistry in the tumours of both groups. RESULTS There were statistically significant differences in tumour grade, stage and occurrence between the ,young' and ,elderly' groups. The ,young' group had a longer disease-free interval to recurrence. Among the immunohistochemical markers analysed, only MIB-1 and cyclin D1 were associated with an increased risk of recurrence in the ,young' group (P < 0.04 and <0.01, respectively) in a univariate analysis. CONCLUSIONS Superficial papillary urothelial tumours of the bladder in ,young' patients had a better prognosis than those in the ,elderly' group, showing a lower grade and stage at diagnosis, and a lower recurrence rate. Proliferative activity and cyclin D1 expression levels were of prognostic significance for the risk of recurrence in these patients. [source]

Outcome after radical prostatectomy with a pretreatment prostate biopsy Gleason score of ,8

BJU INTERNATIONAL, Issue 6 2003
M. Manoharan
The use of radical prostatectomy to treat patients with high-grade prostate cancer is the subject of much discussion, and the authors from Miami present their considerable experience in this field. They show that patients with a pre-treatment biopsy of Gleason score of ,8 may benefit from radical prostatectomy, assuming a clinical stage of T1,T2, and particularly if their PSA level is <20 ng/mL. Authors from Palermo present data on the long-term outcome of antiandrogen monotherapy in advanced prostate cancer, with the 12-year results of a phase II study. This is a very interesting evaluation, showing that patients with an early objective response have a prolonged progression-free and overall survival. In a large series of superficial bladder tumours, urologists from Tokyo identify a group of patients with tumours of low malignant potential with a high recurrence rate, but a very low invasive property. They suggest that those tumours should be referred to as having a low malignant potential, rather than being called superficial bladder carcinoma. OBJECTIVE To determine the outcome and predictors of recurrence in patients with a pretreatment prostate biopsy Gleason score (GS) of ,,8 and treated with radical prostatectomy (RP). PATIENTS AND METHODS We retrospectively reviewed 1048 consecutive patients who underwent RP by one surgeon (M.S.S.); patients who had a pretreatment biopsy GS of ,,8 were identified. Information was recorded on patient age, initial prostate specific antigen (PSA) level, clinical stage, biopsy GS, pathology GS, extraprostatic extension (EPE), tumour volume, surgical margin status, seminal vesicle invasion (SVI), and lymph node involvement. The results were assessed statistically using the Kaplan-Meier method, univariate log-rank tests and multivariate analysis using Cox's proportional hazards regression. RESULTS In all, 123 patients met the initial selection criteria; 44 were excluded from further analyses (five salvage RP, 23 <,1 year follow-up and 16 adjuvant treatment). Thus 79 patients were included in the uni- and multivariate analyses; 25 (31%) patients had a GS of ,,7 in the RP specimen and 54 (69%) remained at GS ,,8. The mean follow-up was 55 months, the age of the patients 63 years and the mean (sd) initial PSA level 13 (12) ng/mL. The overall biochemical failure rate was 38% (41% if the final GS was , 8 and 32% if it was ,,7). For those with a GS of ,,8 in the RP specimen, 20% (11/54) were organ-confined; two patients (2.5%) in this group developed local recurrence. If the final GS was ,,7, 52% (13/25) were organ-confined. In the univariate analysis, significant risk factors for recurrence were PSA ,,20 ng/mL, EPE, SVI, a positive surgical margin and tumour volume. Cox's proportional regression indicated that a PSA of ,,20 ng/mL (hazard ratio 7.9, 95% confidence interval 2.6,24.2, P < 0.001), the presence of EPE (4.2, 1.6,10.9, P = 0.004) and a positive surgical margin (3.8, 1.5,9.7, P = 0.005) were significant independent predictors in a multivariate analysis. CONCLUSION RP is a reasonable treatment option for patients with a prostate biopsy GS of ,8 and clinical stage T1,2. These patients have a high chance of remaining disease-free if their PSA level is ,,20 ng/mL. Patients with a pretreatment biopsy GS of ,,8 should be counselled about the potential differences between the biopsy and the RP specimen GS. [source]

Superficial bladder tumours: analysis of prognostic factors and construction of a predictive index

BJU INTERNATIONAL, Issue 4 2003
B. Ali-El-Dein
OBJECTIVES To assess the prognostic factors that could be used to predict tumour recurrence and progression, and to construct and validate a predictive index. PATIENTS AND METHODS Between June 1991 and December 2000, 533 patients (418 men and 115 women; mean age 55.4 years) underwent complete transurethral resection of histologically confirmed pTa and pT1 transitional cell carcinoma of the bladder, after which 377 (test series) were randomized into two subsequent studies, of six groups, to receive adjuvant intravesical sequential bacillus Calmette-Guérin (BCG) and epirubicin, BCG alone, epirubicin (50 or 80 mg), adriamycin 50 mg or no adjuvant therapy. Factors potentially affecting tumour recurrence or progression were assessed using univariate and multivariate analysis, i.e. tumour stage, histological grade, DNA ploidy, history of recurrence, multiplicity, size, tumour configuration, associated carcinoma in situ, recurrence at the first 3-month check cystoscopy and the use of adjuvant therapy. The regression coefficients determined by Cox regression analysis were used to construct a predictive index (PI). The algebraic sum of the regression coefficients of the factors with independent and significant association with disease-free survival for each case represented a proportional hazard score (PHS). The PI was validated in another series of 156 patients (validation series) in whom the same regression coefficients for the same significant factors as the test series were used to categorize it into three risk groups. Kaplan-Meier survival curves were plotted to compare the different risk categories in both test and validation series. RESULTS The mean (sd, range) follow-up in the test and validation series were 58 (19, 5,96) and 28.3 (14.9, 2,94) months, respectively. In the test series, tumour stage, DNA ploidy, multiplicity, history of recurrence, tumour configuration, cystoscopy result and the type of adjuvant therapy had independent significance for recurrence on multivariate analysis. For progression, the cystoscopy result, DNA ploidy and grade were the only independent and significant predictors. The ranges of PHS for the factors affecting recurrence-free and progression-free survival were 0.0,7.14 and 0.0,5.84, respectively, which were divided equally into three risk categories with significant differences on Kaplan-Meier curves and a log-rank test (P < 0.001). The three categories in the validation series were significantly different from each other and each was comparable with that in the test series. CONCLUSIONS Tumour stage, DNA ploidy, multiplicity, history of recurrence, tumour configuration and type of adjuvant therapy affected independently the rate of recurrence after resecting superficial bladder tumour. Recurrence at the 3-month cystoscopy, histological grade and DNA ploidy were the only predictors of progression to muscle-invasion. The PI dividing the patients into three risk groups with different treatment and follow-up strategies for recurrence and progression was reproducible in a validation series. [source]

Matrix metalloproteinases (MMPs) in bladder cancer: the induction of MMP9 by epidermal growth factor and its detection in urine

BJU INTERNATIONAL, Issue 1 2003
J.E. Nutt
OBJECTIVES To investigate the matrix metalloproteinases (MMPs) 2 and 9 in bladder cancer cell lines stimulated with epidermal growth factor (EGF), and to investigate the presence of gelatinases in the urine of patients with bladder tumours, in relation to the stage and grade of tumour and the EGF receptor (EGFR) status. PATIENTS, SUBJECTS AND METHODS Conditioned media from cultured tumour cells were analysed by zymography. Urine samples from 28 patients with transitional cell carcinoma and 12 normal volunteers were also analysed. Western blotting was used to verify the bands of gelatinolytic activity. The EGFR status of the tumours was assessed by immunohistochemistry. RESULTS MMP9 was induced by EGF in the RT112 but not the RT4 bladder tumour cell line, whereas MMP2 production was unaffected by EGF. Gelatin zymography of urine samples from patients with bladder tumours showed high levels of MMP activity, with 78% positive for MMP9 and 28% positive for MMP2. The total gelatinolytic and MMP9 activity were significantly higher in patients with high-stage invasive tumours than in those with superficial tumours (P < 0.05), and were higher than in normal controls. Gelatinolytic activity at 130 and 200 kDa in urine was identified as MMP9 and MMP2. There was no significant relationship of urinary MMP9 activity to EGFR status of the tumour. CONCLUSION EGF induces MMP9 but not MMP2 in bladder cells. Analysis of urinary gelatinases is a useful noninvasive technique and both total gelatinase and MMP9 activity are associated with high stages of bladder tumours. [source]

Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette-Guérin (Danish 1331 strain)

BJU INTERNATIONAL, Issue 6 2002
J.N. Kulkarni
Objective ,To report recurrence and progression rates in patients with T1G3 superficial bladder carcinoma treated with intravesical bacille Calmette-Guérin (BCG, Danish 1331 strain) after complete transurethral resection. Patients and methods ,Data from the records of 111 patients with T1G3 bladder carcinoma treated between January 1991 and December 1999 were analysed for recurrence, progression, salvage therapy and survival. Results ,Of the 111 patients with T1G3 bladder tumours, 69 had intravesical BCG therapy, 20 radical cystectomy and 22 only transurethral resection (TUR). Of the 69 patients receiving BCG therapy 37 (54%) had no recurrence, and 24 (35%) had a recurrence that was not muscle-invasive (Ta/T1) and were treated with TUR only. The remaining eight (12%) progressed to muscle invasion and had salvage cystectomy. During the follow-up six patients died, four from disease and three from other causes, while the remaining 63 are alive and well. Of the other 42 patients, 15 are alive after radical cystectomy and 18 after TUR. Conclusion ,This series further confirms the benefits of intravesical BCG (Danish 1331) in an adjuvant setting; furthermore, this treatment facilitates bladder preservation by reducing recurrences and delaying the progression in many patients. [source]

Imaging for staging bladder cancer: a clinical study of intravenous 111indium-labelled anti-MUC1 mucin monoclonal antibody C595

BJU INTERNATIONAL, Issue 1 2001
O.D.M. Hughes
Objective To investigate the clinical application of an 111In-labelled anti-MUC1 mucin monoclonal antibody (mAb) imaging for staging invasive bladder cancer. Patients and methods Indirect immunohistochemistry was used to confirm the expression of the MUC1 target antigen by metastatic tumours. Twelve patients with bladder cancer (two with superficial and 10 with locally invasive/metastatic disease) underwent planar ,-scintigraphy 48 h after an intravenous injection with 111In-labelled anti-MUC1 mucin mAb C595. Results No bladder uptake was detected in the two patients with superficial disease, but scintigraphy showed primary and recurrent bladder tumours and metastases in nine of the remaining 10 patients with invasive disease. In three patients additional staging information was obtained from the mAb imaging which would have altered patient management. There were no reported side-effects. Conclusion This study confirmed the ability of the mAb technique to detect both primary and recurrent invasive bladder tumours and distant metastases. Some lesions shown by mAb imaging were not detected by other methods. The use of mAb imaging has the potential to improve clinical staging and assist in selecting those patients most likely to benefit from radical therapy. [source]

Telomerase activity as a potential marker in preneoplastic bladder lesions

BJU INTERNATIONAL, Issue 4 2000
F. Lancelin
Objective To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis. Patients and methods Tissue telomerase activity was assayed by two different techniques, the telomeric repeat amplification protocol-polymerase chain reaction (TRAP-PCR) and a telomerase PCR-enzyme linked immunosorbent assay. Malignant and inflammatory bladder lesions and their adjacent normal tissues were assessed for telomerase activity in a group of 18 patients, 14 of whom had urothelial carcinoma and four a nonspecific inflammatory lesion of the bladder. Results Eleven of the 14 tumour samples analysed were telomerase-positive and two of the three telomerase-negative tumour samples had a detectable ,telomerase inhibitor'. In the apparently normal tissues next to bladder tumours, four of the 14 specimens were telomerase-positive. Interestingly, these lesions were always next to high-grade muscle-invasive bladder tumours (pT2G3). Two of the four nonspecific inflammatory lesions (one of cystitis glandularis and one of severe dysplasia), known to be preneoplastic lesions, were also telomerase-positive. Conclusion These results strongly suggest that the reactivation of telomerase may be an early event in bladder carcinogenesis, preceding morphological changes related to malignant transformation. Telomerase activity may therefore be useful both as an indicator of malignant potential in preneoplastic lesions, e.g. cystitis glandularis and severe dysplasia, and as a prognostic marker of bladder tumour relapse or progression. [source]