|
| ||
|
|
||
Bladder Carcinoma (bladder + carcinoma)
Kinds of Bladder Carcinoma Selected AbstractsAge and comorbidity impact surgical therapy in older bladder carcinoma patients,,CANCER, Issue 8 2005A population-based study Abstract BACKGROUND Bladder carcinoma often occurs in older patients who also may have other comorbid conditions that could influence the administration of surgical therapy. The current study was conducted to describe the distribution of comorbid conditions in patients with bladder carcinoma and ascertain whether these conditions, as grouped by the American Society of Anesthesiologists physical status classification, affected the choice of surgical therapy. METHODS The authors examined six population-based cancer registries from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program in 1992. A total of 820 individuals age 55 years and older was found. A random sample of newly diagnosed bladder carcinoma patients were stratified according to registry, age group (ages 55,64 yrs, ages 65,74 yrs, and age 75 yrs and older), and gender. Data regarding comorbid conditions were abstracted from the medical records and merged with routinely collected cancer registry data. The main outcome measures were the prevalence and distribution of comorbid conditions, American Society of Anesthesiologists physical status classification, and the receipt of cystectomy in patients with muscle invasion. RESULTS Hypertension, chronic pulmonary disease, arthritis, and heart disease were found to affect at least 15% of the study population. Approximately 38% of patients were current or former smokers. Greater than 90% of patients with superficial disease were treated with transurethral resection alone. Among those patients with muscle invasion, only 55% of those ages 55,59 years underwent cystectomy; this percentage dropped to 4% in patients age 85 years and older. Among patients with an American Society of Anesthesiologists physical status classification of 0,2, the cystectomy rate ranged from 53% in those ages 55,59 years to 9% in those age 85 years and older. CONCLUSIONS There were no significant treatment differences noted with regard to age among patients with superficial disease. Among those patients with muscle invasion, those age 75 years and older were less likely to undergo radical cystectomy (14%) compared with patients ages 55,64 years (48%) and those ages 65,74 years (43%). Patient age may contribute to treatment decisions in patients with muscle-invasive disease, even when comorbidity is taken into account. Cancer 2005. © 2005 American Cancer Society. [source] Human BLCAP transcript: new editing events in normal and cancerous tissuesINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Federica Galeano Abstract Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP -editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors. [source] Invasive bladder carcinoma: A pilot study of conservative treatment with accelerated radiotherapy and concomitant cisplatin,INTERNATIONAL JOURNAL OF CANCER, Issue 6 2001Abderrahim Zouhair M.D. Abstract From November 1992 to December 1997, 25 patients (inoperable or refusing cystectomy) were included in a prospective study to assess the feasibility, tolerance, and curative potential of accelerated radiotherapy (RT) and concomitant cisplatin. Median age was 74 years (range 49,86). Stage distribution was as follows: 1 T1, 10 T2, 8 T3, and 6 T4. Two patients had clinically positive pelvic nodes. The goal was to deliver a total dose of 40 Gy to the whole pelvis and bladder in 4 weeks using a concomitant boost of 20 Gy to the tumor or to the whole bladder during the third and fourth weeks (total dose 60 Gy), with daily cisplatin (6 mg/m2) before RT for patients with creatinine clearance > 50 ml/min. All but one patient completed the RT protocol. Daily cisplatin was sucessfully delivered in 18 patients. One patient presented with grade III ototoxicity. Diarrhea was scored grade III in two and grade IV in two patients. Acute urinary toxicity was scored grade III in one patient. Posttreatment late effects included bladder grade II and grade III in two patients and one patient, respectively; large bowel grade III in one; urethral grade III in one; and femoral head radionecrosis in one. Four-year overall and disease-specific survival rates were 23% and 35%, respectively. The latter was 60% for patients with T2 tumors. The 4-year actuarial locoregional control rate for all patients was 61%. In summary, accelerated RT and concomitant cisplatin is feasible with acceptable tolerance even in relatively old patients. Although outcome was better for patients with low-stage tumors, local control and survival rates appeared similar to those of standard RT schedules for a similar patient population. © 2001 Wiley-Liss, Inc. [source] Reduction of major histocompatibility complex class I expression on bladder carcinoma following tumor antigen-pulsed dendritic cell vaccine: Implications for immunoresistance in therapyINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2010Mengqiang Li Objectives: To clarify the relationship between a decreased major histocompatibility complex class I (MHC-I) expression on bladder tumors and decreased immunological efficacy of tumor antigen-pulsed dendritic cell vaccine in a rat bladder carcinoma model induced by N-methyl-N-nitrosourea irrigation. Methods: Enzyme-linked immunosorbent assay was used to evaluate interferon-gamma concentration in the serum and colorimetric lactate dehydrogenase release assay in vitro was used to test the cytotoxicity capability of T lymphocytes. MHC-I expression on tumor cells was detected by flow cytometry and analyzed with CellQuest software. Results: The tumor antigen sensitized dendritic cell vaccine group showed decreased hyperplastic formations, lower pathological stages in rat bladders and more potent cytotoxicity activity (P < 0.001) than the dendritic cell vaccine group. Additionally, immunization with pulsed dendritic cell vaccine induced higher specific cytokine production of interferon-gamma. Nevertheless, a decreased MHC-I expression on bladder tumors was tested after immunotherapy by pulsed dendritic cell vaccine on week 15. As expected, the cytotoxic activity of T lymphocytes from rats on tumor cells with low MHC-I expression was also decreased to 19.70 ± 4.82% as compared with tumor cells with high MHC-I (52.10 ± 8.66%, P = 0.005). Conclusions: Tumor antigen sensitized dendritic cell vaccine has beneficial activity on N-methyl-N-nitrosourea-induced bladder cancer in situ in rats, but therapeutic responses are accompanied by decreased MHC-I expression on tumors, possibly suggesting poor long-term therapeutic outcomes. [source] Value of selective upper tract cytology for recognition of upper tract tumors after treatment of superficial bladder cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2003ATAY GÖ Abstract Background: The value of selective upper urinary tract (UT) cytology in patients who are asymptomatic and tumor free at control cystoscopy after being treated for superficial bladder carcinoma has not been studied. The present study was performed to evaluate the value of selective UT cytology in patients who are tumor free at control cystoscopy after being treated for superficial bladder cancer. Methods: Forty-seven consecutive patients who had undergone definitive surgical treatment for superficial bladder cancer at least 24 months prior and were tumor free at control cystoscopy were evaluated with bladder wash for cytology as well as selective UT urine cytology by catheterization of both ureteral orifices. Of the 47 patients, disease was stage Ta in 30 (63.8%), T1 in 15 (31.9%) and Ta/Tcis in 2 (4.3%). Primary tumor was unifocal in 24 (51.1%) and multifocal in 23 (48.9%) patients. The time elapsed from the initial diagnosis to the last evaluation ranged from 2 to 21 years (mean 5.39). Results: UT cytology was positive in 2 cases. Although, excretory urography (IVP) revealed mild pelvicalicectasis in 1 of these 2 patients, ureterorenoscopy (URS) revealed no abnormality. In the other patient with normal IVP and retrograde pyelography (RGP), URS revealed a ureteral tumor 5 mm in diameter. Although the UT cytology was normal in the remaining 45 patients, IVP revealed right hydronephrosis in 1 patient and URS revealed multiple ureteral tumors. Conclusion: Given the normal appearance of the UT, it is highly unlikely that these patients have tumor in the UT. Thus, during the follow-up of patients with superficial bladder cancer, it is not useful to perform UT select cytology in the absence of any identifiable filling defects in the upper urinary tract. [source] Microscopic hematuria as a screening marker for urinary tract malignanciesINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2001Kazunobu Sugimura Abstract Background: Although a mass screening urinalysis is a widely accepted procedure, it has not yet been shown if microhematuria is an appropriate and useful screening marker for urologic malignancies. Methods: (1) The incidence of hematuria was studied in 113 patients with renal cell carcinoma (RCC), 185 with bladder carcinoma and 51 with renal pelvic or ureteral carcinoma. The association of the T stage with the intensity of hematuria in each malignancy was also examined. (2) In 823 asymptomatic adults with microhematuria, the prevalence of these malignancies was studied retrospectively to find the positive predictive value (PPV). Results: (1) The incidence of hematuria was 35% for RCC, including gross and microhematuria. Advanced RCC (T3 and T4) were diagnosed more frequently in the gross hematuria group than in the microhematuria and no hematuria groups. In contrast, the incidence of hematuria was 94% for urothelial carcinomas either in the upper urinary tract or in the bladder. There was no significant difference in the T stage nor grade between the gross hematuria group and the microhematuria group. (2) Regarding asymptomatic microhematuria, the PPV was 1.7% (14 cases) for bladder carcinoma, 0.4% (3 cases) for ureteral/renal pelvic carcinoma and 0.2% (2 cases) for RCC. In men aged 50 years or older, PPV was 6.2% for urothelial carcinomas. In 14 cases of bladder carcinoma, 3 cases showed muscle invasion. Conclusions: Microhematuria is an appropriate screening marker for urothelial carcinomas, particularly in elderly men, but not for RCC. However, it is unlikely that a mass screening urinalysis using a single voided urine sample would contribute to earlier detection of bladder carcinoma. [source] Preoperative diagnosis of bilateral tuberculous epididymo-orchitis following intravesical Bacillus Calmette,Guerin therapy for superficial bladder carcinomaJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 2 2002Malai Muttarak SUMMARY We report a case of bilateral tuberculous epididymo-orchitis following intravesical Bacillus Calmette,Guerin (BCG) therapy for superficial bladder carcinoma in which the diagnosis was made by ultrasonography prior to surgery. The US findings include heterogeneous enlargement of the epididymis and testis, associated with scrotal-skin thickening and scrotal sinus track. Patients with bladder carcinoma treated with intravesical BCG therapy, the presence of scrotal swelling with scrotal-skin thickening and epididymal involvement suggests tuberculous epididymo-orchitis rather than testicular tumour. It is important to be aware of this rare complication and to be familiar with the ultrasonographic features so that appropriate treatment can be given. [source] Phytochemicals in olive-leaf extracts and their antiproliferative activity against cancer and endothelial cellsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2009Vlassios Goulas Abstract Olive oil compounds is a dynamic research area because Mediterranean diet has been shown to protect against cardiovascular disease and cancer. Olive leaves, an easily available natural material of low cost, share possibly a similar wealth of health benefiting bioactive phytochemicals. In this work, we investigated the antioxidant potency and antiproliferative activity against cancer and endothelial cells of water and methanol olive leaves extracts and analyzed their content in phytochemicals using LC-MS and LC-UV-SPE-NMR hyphenated techniques. Olive-leaf crude extracts were found to inhibit cell proliferation of human breast adenocarcinoma (MCF-7), human urinary bladder carcinoma (T-24) and bovine brain capillary endothelial (BBCE). The dominant compound of the extracts was oleuropein; phenols and flavonoids were also identified. These phytochemicals demonstrated strong antioxidant potency and inhibited cancer and endothelial cell proliferation at low micromolar concentrations, which is significant considering their high abundance in fruits and vegetables. The antiproliferative activity of crude extracts and phytochemicals against the cell lines used in this study is demonstrated for the first time. [source] Development of secondary myelodysplastic syndrome in a patient with previous bladder carcinomaAMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2006Ahmet Ifran No abstract is available for this article. [source] Searching cell-secreted proteomes for potential urinary bladder tumor markersPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 15 2006Chiao-Yun Lin Abstract To search for biomarkers critical for bladder carcinoma diagnosis and prognosis, secreted proteomes of highly malignant U1 and pre-malignant U4 cell lines were initially analyzed. Proteins in the culture media of the U1 and U4 cell lines were systematically examined by SDS-PAGE combined with MALDI-TOF MS. Among them, expression of pro-u-plasminogen activator (pro-u-PA) was confirmed by Western blot analysis and further evaluated. In analyzing urine samples from bladder cancer patients and normal subjects, we established a statistically significant relationship between the low level and absence of pro-u-PA in urine with high stages and grades of the tumor samples. Constitutive expression of Ras dominant negative protein led to increased expression of pro-u-PA in culture media, indicating that the loss of pro-u-PA is associated with oncogenic transformation. Analysis of cancer-secreted proteomes can be a feasible, non-invasive and efficient strategy for searching potential bladder tumor biomarkers. Our work also has identified the loss of pro-u-PA in urine as potential marker of more advanced bladder carcinoma. [source] Cyclooxygenase-2 expression on urothelial and inflammatory cells of cystoscopic biopsies and urine cytology as a possible predictive marker for bladder carcinomaAPMIS, Issue 1 2009MONA MOUSSA Cyclooxygenase-2 (COX-2) is a key inducible enzyme involved in the production of prostaglandins. It contributes to human carcinogenesis by various mechanisms. The aim of the current study was to elucidate the possible involvement of COX-2 in human bladder carcinoma by examining its expression on both urothelial and inflammatory cells in tissue biopsies and urine cytology samples of different urinary bladder lesions. A total of 65 patients were included in the study and were selected from cases admitted to Urology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt. They represented seven control cases with almost normal-looking bladder tissue; pure chronic cystitis (n=12); premalignant lesions (18) in the form of squamous metaplasia (n=8) or urothelial dysplasia (n=10) as well as transitional cell carcinoma (TCC) (n=18), and squamous cell carcinoma (SqCC) (n=10). Immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections and urine cytology samples was performed for all cases using COX-2 (H-62): sc-7951, a rabbit polyclonal antibody. The study revealed positive COX-2 expression on the urothelial and inflammatory cells of cystoscopic biopsies from all cases of pure chronic cystitis, squamous metaplasia and SqCC compared with 42.8% and 71.4% of normal controls, respectively. The score of urothelial COX-2 expression was sequentially up-regulated from normal to chronic cystitis (either pure or associated with premalignant changes) (p<0.05) to malignant changes (p<0.05). However, the inflammatory cellular expression was down-regulated with malignant transformation compared with chronic cystitis (p<0.05). In TCC, COX-2 was over-expressed on both urothelial and inflammatory cells in advanced tumors. Urine cytology samples were positive for COX-2 in a comparable manner to that observed in cystoscopic biopsies. Accordingly, the results of the current study have provided new information in two aspects: First, is the possibility of using the differential COX-2 expression on both inflammatory and urothelial cells as markers for premalignant or malignant transformation; second, besides cystoscopy, urine cytology was found to have a high sensitivity for COX-2 expression and hence proved to be valuable in malignancy as a non-invasive substitute for cystoscopy. [source] Predicting outcome in minimally invasive (T1a and T1b) urothelial bladder carcinoma using a panel of biomarkers: a high throughput tissue microarray analysisBJU INTERNATIONAL, Issue 5 2007Paulette Mhawech-Fauceglia OBJECTIVE To evaluate the protein expression of fibroblast growth factor receptor-3 (FGFR3), hamartin, 14-3-3,, Aurora-A, and E-cadherin using immunohistochemistry (IHC) in a series of human bladder carcinomas and to evaluate their value in distinguishing T1a from T1b tumours and in predicting their behaviour, as T1 urothelial bladder tumours present great diagnostic and therapeutic challenges to pathologists and clinicians. PATIENTS, MATERIALS AND METHODS Tissue microarrays were constructed from 94 patients (Ta 20, T1a 31, T1b 14, and T2 29 patients) using tissue obtained at first disease presentation. RESULTS FGFR3 and 14-3-3, were the only markers that were significantly associated with tumour grade and 14-3-3, was significantly associated with tumour stage. Furthermore, none of these markers could help in distinguishing T1a from T1b tumours. After adjusting for the E-cadherin expression, FGFR3 expression was a significant factor in predicting the time to recurrence in T1a/T1b. Furthermore, among all the clinical variables, grade and depth of invasion were the only ones that had a significant value in predicting T1a/T1b tumour progression. CONCLUSIONS Even though the staging of T1 to T1a/T1b is not a common practice and it is not included in the Tumour-Node-Metastasis classification, our data clearly confirmed the importance of a proper sub-staging of T1 tumours whenever feasible. [source] Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastasesBJU INTERNATIONAL, Issue 7 2005Truls Gårdmark OBJECTIVE To evaluate the expression of HER2 receptors (previously reported to be over-expressed in malignant urothelium) in both primary tumours and metastases of transitional cell cancer, using two different staining methods and two different scoring techniques, considering the potential use of these receptors as targets for planned systemic anti-HER2 nuclide-based treatment. MATERIALS AND METHODS HER2 expression was evaluated with two different immunohistochemical methods in 90 patients with primary urinary bladder cancer tumours and corresponding metastases. Sections were first stained with the commercially available breast cancer test kit (HercepTest®, Dako, Glostrup, Denmark). Parallel sections were then stained with a modified HercepTest procedure. Two different evaluation criteria were compared; the HercepTest score that requires ,,10% stained tumour cells (as for breast cancer) and a proposed ,Target score' that requires >67% stained tumour cells. The latter score is assumed to be preferable for HER2-targeted radionuclide therapy. RESULTS Using the HercepTest kit, the Target score gave lower fractions of positive primary tumours and metastases than the HercepTest score. The modified HercepTest staining procedure and Target score gave high HER2 values in 80% of primary tumours and 62% of metastases, which is considerably more than that obtained with the HercepTest staining and score. There was a significant decrease in HER2 positivity with increasing distance from the primary tumour. In nine sentinel-node metastases assessed, all but one were HER2-positive. Considering all regional metastases, 74% were positive, and of distant metastases, 47%; 72% of the patients with positive primary tumours also expressed HER2 in their metastases. CONCLUSIONS When combining the modified HercepTest with customised evaluation criteria, more HER2-positive tumours were diagnosed. The degree of HER2 down-regulation was significantly higher in distant than in regional metastases. HER2-targeted therapy may be an alternative or complementary to other methods in the future treatment of metastatic urinary bladder carcinoma. [source] Correlation between clinical and pathological staging in a series of radical cystectomies for bladder carcinomaBJU INTERNATIONAL, Issue 6 2005Vincenzo Ficarra OBJECTIVE To analyse the rate of concordance between the clinical and pathological Tumour-Nodes-Metastasis staging systems in a homogeneous series of patients who had undergone radical cystectomy for locally advanced or recurrent multifocal superficial bladder carcinoma. PATIENTS AND METHODS The clinical data of 156 patients who had undergone radical cystectomy and bilateral iliaco-obturator lymphadenectomy for bladder cancer in our department were analysed retrospectively. RESULTS The clinical stage of the primary tumour was carcinoma in situ in three patients (1.9%), cT1 in 67 (42.9%), cT2 in 70 (44.9%), cT3 in five (3.2%) and cT4 in nine (5.8%). Clinical lymph node involvement was detected in 19 patients (12.2%). The differences between clinical and pathological stages were statistically significant (P < 0.001), the concordance was moderate (, = 0.27, P < 0.001). Of the 70 patients with ,,cT1, 40 (57%) were reconfirmed as having pathological stage ,,T1; of the 70 with cT2, 16 (23%) had pT2 carcinoma. Of the 140 patients with clinically organ-confined (,T2) neoplasms, 70 (50%) had been understaged after radical cystectomy. The clinical and pathological systems were statistically overlapping for locally advanced cases only. Pathological lymph node involvement was diagnosed in 45 patients (28.8%); this was foreseen with pelvic computed tomography in 19 (12%) only (P < 0.001). All patients designated cN+ were also pN+. CONCLUSION These data confirm the high risk of clinical understaging of both local extension of the primary tumour and lymph node involvement. [source] Outcome after radical prostatectomy with a pretreatment prostate biopsy Gleason score of ,8BJU INTERNATIONAL, Issue 6 2003M. 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] Cyclooxygenase-2 promotes angiogenesis in pTa/T1 urothelial bladder carcinoma but does not predict recurrenceBJU INTERNATIONAL, Issue 4 2003M.G. Friedrich OBJECTIVE To investigate the effect of cyclooxygenase-2 (COX-2) on microvessel density (MVD) and on the clinical prognosis in patients with non-muscle invasive urothelial carcinoma of the bladder, as COX-2 expression is significantly greater in epithelial tumours and there is increasing evidence that COX-2 might contribute to tumour neovascularization. PATIENTS AND METHODS We assessed tumour samples from 110 patients undergoing transurethral resection for primary pTa/pT1 bladder carcinoma (pTa, 84; pT1, 26; grade 1, 22; grade 2, 81; grade 3, seven). Paraffin sections were assessed immunohistochemically using antibodies against COX-2, CD34 (endothelial cells) and CD105 (proliferating vessels). COX-2 expression was quantified by the number of stained cells (negative, +, ++) and the MVD calculated as vessels per field. RESULTS Of the 110 tumours, 45 (41%) had no immunostaining for COX-2, 40 had faint staining with at least isolated positive cells (+) and 25 stained ++. COX-2 positive tumours had significantly greater vascularization for proliferating vessels. In COX-2 negative tumours the MVD was 22.1, identified by CD34 immunostaining, and 3.4 for proliferating vessels (CD105), whereas COX-2 positive tumours had a MVD of 18.3 (CD34), and of 5.8, respectively (CD105). Complete follow-up data were available in 91 patients; after a mean follow-up of 25 months, 18 (20%) had tumour recurrences. There was no significant difference in the recurrence rates or disease-free survival between COX-2-positive (19%, 25.6 months) or -negative patients (21%, 25.2 months). CONCLUSION These results confirm the involvement of COX-2 in angiogenesis in bladder cancer, as COX-2 promoted blood vessel proliferation in the tumour zone, and indicate the usefulness of COX-2-inhibiting drugs in preventing and treating superficial bladder cancer. [source] Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette-Guérin (Danish 1331 strain)BJU INTERNATIONAL, Issue 6 2002J.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] Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin SBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009JD Mitchell Neuromedin U (NMU) has been paired with the G-protein-coupled receptors (GPRs) NMU1 (formely designated as the orphan GPR66 or FM-3) and NMU2 (FM-4 or hTGR-1). Recently, a structurally related peptide, neuromedin S (NMS), which shares an amidated C-terminal heptapeptide motif, has been identified in both rat and human, and has been proposed as a second ligand for these receptors. Messenger RNA encoding NMU receptor subtypes shows differential expression: NMU1 is predominantly expressed in peripheral tissues, particularly the gastrointestinal tract, whereas NMU2 is abundant within the brain and spinal cord. NMU peptide parallels receptor distribution with highest expression in the gastrointestinal tract and specific structures within the brain, reflecting its major role in the regulation of energy balance. The NMU knockout mouse has an obese phenotype and, in agreement, the Arg165Trp amino acid variant of NMU-25 in humans, which is functionally inactive, co-segregated with childhood-onset obesity. Emerging physiological roles for NMU include vasoconstriction mediated predominantly via NMU1 with nociception and bone remodelling via NMU2. The NMU system has also been implicated in the pathogenesis of septic shock and cancers including bladder carcinoma and acute myeloid leukaemia. Intriguingly, NMS is more potent at NMU2 receptors in vivo where it has similar central actions in suppression of feeding and regulation of circadian rhythms to NMU. Taken together with its vascular actions, NMU may be a functional link between energy balance and the cardiovascular system and may provide a future target for therapies directed against the disorders that comprise metabolic syndrome. [source] Age and comorbidity impact surgical therapy in older bladder carcinoma patients,,CANCER, Issue 8 2005A population-based study Abstract BACKGROUND Bladder carcinoma often occurs in older patients who also may have other comorbid conditions that could influence the administration of surgical therapy. The current study was conducted to describe the distribution of comorbid conditions in patients with bladder carcinoma and ascertain whether these conditions, as grouped by the American Society of Anesthesiologists physical status classification, affected the choice of surgical therapy. METHODS The authors examined six population-based cancer registries from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program in 1992. A total of 820 individuals age 55 years and older was found. A random sample of newly diagnosed bladder carcinoma patients were stratified according to registry, age group (ages 55,64 yrs, ages 65,74 yrs, and age 75 yrs and older), and gender. Data regarding comorbid conditions were abstracted from the medical records and merged with routinely collected cancer registry data. The main outcome measures were the prevalence and distribution of comorbid conditions, American Society of Anesthesiologists physical status classification, and the receipt of cystectomy in patients with muscle invasion. RESULTS Hypertension, chronic pulmonary disease, arthritis, and heart disease were found to affect at least 15% of the study population. Approximately 38% of patients were current or former smokers. Greater than 90% of patients with superficial disease were treated with transurethral resection alone. Among those patients with muscle invasion, only 55% of those ages 55,59 years underwent cystectomy; this percentage dropped to 4% in patients age 85 years and older. Among patients with an American Society of Anesthesiologists physical status classification of 0,2, the cystectomy rate ranged from 53% in those ages 55,59 years to 9% in those age 85 years and older. CONCLUSIONS There were no significant treatment differences noted with regard to age among patients with superficial disease. Among those patients with muscle invasion, those age 75 years and older were less likely to undergo radical cystectomy (14%) compared with patients ages 55,64 years (48%) and those ages 65,74 years (43%). Patient age may contribute to treatment decisions in patients with muscle-invasive disease, even when comorbidity is taken into account. Cancer 2005. © 2005 American Cancer Society. [source] Detection of bladder carcinoma by combined testing of urine for hyaluronidase and cytokeratin 20 RNAsCANCER, Issue 7 2005Ph.D., Sanaa Eissa M.D. Abstract BACKGROUND A new, sensitive, noninvasive method for the detection of urothelial carcinomas of the urinary bladder would open new possibilities in both the diagnosis and followup of patients. METHODS This study included 228 patients diagnosed with bladder carcinoma, 68 patients with benign bladder lesions, and 44 healthy persons served as the control group. All were subjected to: serologic schistosomiasis antibody assay in serum, urine cytology, estimation of urine hyaluronic acid (HA) by enzyme-linked immunosorbent assay, and detection of CK-20 and hyaluronidase (HAase) by reverse transcription polymerase chain reaction (RT-PCR) in urothelial cells from voided urine. RESULTS HA mean rank was higher in benign and malignant groups than in the healthy group (P < 0.0001) and was significantly related to tumor grade (P = 0.021). HA best-cutoff, determined using receiver operating characteristic curve to discriminate between malignant and nonmalignant groups, was 58.5 units/mg protein at 85.8% sensitivity and 60.7% specificity. HAase RNA showed superior sensitivity (90.8%) over cytology (68.9%) and CK-20 (78.1%) with specificity of 93.4%, 98.1% and 80.2%, respectively. The sensitivity reached 94.7% at a specificity of 91.5% when combined with CK-20. All 4 of the investigated markers were related to grade at P <0.05. Whereas only HAase and CK-20 were significantly related to stage (P < 0.05). As to schistosomiasis, only HAase RNA positivity was significantly associated (P = 0.038). CONCLUSIONS HAase RNA is a promising noninvasive test with high sensitivity and specificity in bladder carcinoma detection. Cancer 2005. © 2005 American Cancer Society. [source] Phase I trial of weekly docetaxel and gemcitabine in patients with refractory malignanciesCANCER, Issue 1 2003M.Sc., Tarek Mekhail M.D. Abstract BACKGROUND A Phase I study using weekly docetaxel and gemcitabine was conducted to investigate toxicity; to determine the maximum tolerated dose (MTD) of each agent; and, in a preliminary fashion, to determine the antitumor activity of the combination. METHODS Docetaxel and gemcitabine were administered intravenously on Days 1, 8, and 15 every 28 days. The dose levels of docetaxel and gemcitabine were as follows: Level I, docetaxel 20 mg/m2and gemcitabine 400 mg/m2; Level II, docetaxel 30 mg/m2and gemcitabine 400 mg/m2; Level III, docetaxel 30 mg/m2and gemcitabine 600 mg/m2; Level IV, docetaxel 36 mg/m2and gemcitabine 600 mg/m2; and Level V, docetaxel 36 mg/m2and gemcitabine 800 mg/m2. RESULTS Thirty-three eligible patients were entered. The diagnoses were as follows: Eleven patients had nonsmall cell lung carcinoma, 3 patients had carcinoma of the bladder, 3 patients had renal carcinoma, 2 patients had adrenal carcinoma, 5 patients had unknown primary tumors, and 9 patients had miscellaneous malignancies. Fifty-nine percent of patients had received prior chemotherapy. The median age was 62 years (range, 27,77 years), and the median Eastern Cooperative Oncology Group performance status was 1 (range, 0,1). Five patients were treated at Dose Levels I and II, 6 patients were treated at Dose Levels III and V, and 11 patients were treated at Dose Level IV. Grade 3,4 toxicities during Cycle I included neutropenia, thrombocytopenia, mucositis, and diarrhea. Dose-limiting toxicity, consisting of neutropenia and thrombocytopenia, occurred in three of six patients at Dose Level V. The combination of docetaxel 36 mg/m2 and gemcitabine 600 mg/m2 (Dose Level IV) was determined as the MTD and was the recommended Phase II dose. Two patients had a partial response: one patient with bladder carcinoma (Dose Level II) and one patient with nonsmall cell lung carcinoma (Dose Level III). CONCLUSIONS Overall, weekly docetaxel and gemcitabine were well tolerated. Further studies using this combination are planned, including a Phase II trial in patients with advanced nonsmall cell lung carcinoma. Cancer 2003;97:170,8. © 2003 American Cancer Society. DOI 10.1002/cncr.10991 [source] Randomized study of single early instillation of (2,R)-4,- O -tetrahydropyranyl-doxorubicin for a single superficial bladder carcinomaCANCER, Issue 9 2002Kikuo Okamura M.D., Ph.D. Abstract BACKGROUND Although transurethral resection of a bladder tumor (TUR-Bt) alone has been standard treatment for single superficial bladder carcinoma, some authors reported a certain prophylactic effect of a single immediate intravesical instillation of chemotherapeutic agent after TUR-Bt. A prospective randomized study was conducted to determine whether a single (2,R)-4,- O -tetrahydropyranyl-doxorubicin (THP) instillation immediately after TUR-Bt is beneficial to patients with a single superficial bladder carcinoma. METHODS One hundred seventy patients with a single resectable superficial bladder carcinoma (Ta-1, primary or recurrent with no recurrence during the last 1 year) were enrolled in this study. THP (30 mg/30 mL of normal saline) was administered into the bladder within 6 hours after TUR-Bt in arm A, while TUR-Bt alone was done in arm B. RESULTS Of the 170 patients, 160 (94.1%) were eligible and were followed up for a median time of 40.8 months. There was a significant difference in the recurrence free curve between the 2 arms (log-rank test; P = 0.0026), with 92.4% recurrence free rate at 1 year, 82.7% at 2 years, and 78.8% at 3 years in arm A (84 patients) and 67.0%, 55.7%, and 52.6%, respectively, in arm B. The recurrence rate per year was 0.11 ± 0.22 in arm A and 0.24 ± 0.36 in arm B, with a significant difference (P = 0.007). Toxicity included pain with micturition in 9 patients (10.7%), urinary frequency/urgency in 5 patients (6.0%), and macroscopic hematuria in 7 patients (8.3%). CONCLUSIONS These data indicate that a single THP instillation immediately after TUR reduces the recurrence of superficial bladder carcinoma. Cancer 2002;94:2363,8. © 2002 American Cancer Society. DOI 10.1002/cncr.10496 [source] Precise microdissection of human bladder carcinomas reveals divergent tumor subclones in the same tumorCANCER, Issue 1 2002Liang Cheng M.D. Abstract BACKGROUND Human bladder carcinoma is thought to arise from a field change that affects the entire urothelium. Whether independently transformed urothelial cell populations exist in the same patient is uncertain. METHODS We studied the clonality of urinary bladder carcinoma in 18 female patients who underwent cystectomy for urothelial carcinoma. None had multiple tumors. Tumor samples were obtained from different areas of the same tumor. Sixty-seven tumor samples were analyzed. Tumor genomic DNA was microdissected and extracted from formalin-fixed, paraffin-embedded slides. The clonality of urothelial tumors was evaluated on the basis of a polymorphism of the X chromosome-linked human androgen receptor gene (HUMARA) locus. The technique is dependent on digestion of DNA with the methylation-sensitive restriction enzyme HhaI, polymerase chain reaction (PCR) amplification of HUMARA locus, and detection of methylation of this locus. With this method, only the methylated HUMARA allele is selectively amplified by PCR. RESULTS Eleven of 18 patients were informative. Nonrandom inactivation of the X chromosome was found in 9 of the 11 informative patients (82%). Seven patients showed different patterns of nonrandom X chromosome inactivation for tumor samples obtained from different regions of the same tumor. Two patients showed the same pattern of nonrandom X chromosome inactivation in all samples. CONCLUSIONS Some muscle-invasive urothelial carcinomas may arise from independently transformed progenitor urothelial cells, supporting the "field effect" theory for bladder carcinogenesis. Cancer 2002;94:104,10. © 2002 American Cancer Society. [source] 4254: Infectious and non infectious triggers in non-infectious uveitisACTA OPHTHALMOLOGICA, Issue 2010G WILDNER Purpose The induction of autoimmune uveitis is difficult to explain with respect to the immune privileged status of the eye. The intact BRB can only be passed by already activated leukocytes, which should normally be ignorant to the sequestered intraocular antigens. Antigenic mimicry of retinal autoantigens by environmental proteins could explain extraocular activation of effector T cells. Methods We have previously demonstrated antigenic mimicry of a peptide from retinal S-Antigen and peptides from rotavirus (Rota) and bovine milk casein (Cas). Both, Rota and Cas, induce T cell lines cross-reactive with retinal S-Ag peptide as well as experimental autoimmune uveitis in rats. Patients with uveitis have increased antibody and T cell responses to the mimicry peptides as well as to the S-Ag peptide compared to healthy donors. Accordingly, Infection with rotavirus or any gastrointestinal pathogen with concomitant ingestion of bovine milk products could induce an immune response in the gastrointestinal tract that is cross-reactive with ocular autoantigens and lead to induction of autoimmunity in the eye. Results Uveitis as a well known adverse effect after BCG (Bacille Calmette Guerin) treatment might also be the result of antigenic mimicry. We have shown T cell responses to PPD from M. tuberculosis and the retinal autoantigens S-Ag, IRBP and CRALBP from a patient who had developed granulomatous uveitis after BCG application for bladder carcinoma. Data base searches revealed a number of amino acid sequence homologies between proteins from mycobacteria and retinal autoantigens, suggesting antigenic mimicry. These findings might as well be an explanation for the occurrence of uveitis in connection with M. tuberculosis infection, even when no mycobacteria are detectable in the eye. [source] Predicting outcome in minimally invasive (T1a and T1b) urothelial bladder carcinoma using a panel of biomarkers: a high throughput tissue microarray analysisBJU INTERNATIONAL, Issue 5 2007Paulette Mhawech-Fauceglia OBJECTIVE To evaluate the protein expression of fibroblast growth factor receptor-3 (FGFR3), hamartin, 14-3-3,, Aurora-A, and E-cadherin using immunohistochemistry (IHC) in a series of human bladder carcinomas and to evaluate their value in distinguishing T1a from T1b tumours and in predicting their behaviour, as T1 urothelial bladder tumours present great diagnostic and therapeutic challenges to pathologists and clinicians. PATIENTS, MATERIALS AND METHODS Tissue microarrays were constructed from 94 patients (Ta 20, T1a 31, T1b 14, and T2 29 patients) using tissue obtained at first disease presentation. RESULTS FGFR3 and 14-3-3, were the only markers that were significantly associated with tumour grade and 14-3-3, was significantly associated with tumour stage. Furthermore, none of these markers could help in distinguishing T1a from T1b tumours. After adjusting for the E-cadherin expression, FGFR3 expression was a significant factor in predicting the time to recurrence in T1a/T1b. Furthermore, among all the clinical variables, grade and depth of invasion were the only ones that had a significant value in predicting T1a/T1b tumour progression. CONCLUSIONS Even though the staging of T1 to T1a/T1b is not a common practice and it is not included in the Tumour-Node-Metastasis classification, our data clearly confirmed the importance of a proper sub-staging of T1 tumours whenever feasible. [source] Non-transitional cell bladder carcinomasBJU INTERNATIONAL, Issue 4 2005Andrea Manunta First page of article [source] | ||||||||||||||||||||||||||||