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Urothelial Cancer (urothelial + cancer)
Selected AbstractsSomatic mutations of adenomatous polyposis coli gene and nuclear b-catenin accumulation have prognostic significance in invasive urothelial carcinomas: Evidence for Wnt pathway implicationINTERNATIONAL JOURNAL OF CANCER, Issue 1 2009Efstathios Kastritis Abstract Wnt pathway signaling is crucial in many cancers and data indicate crosstalk with other key cancer pathways, however in urothelial carcinogenesis it has not been extensively studied. We searched for mutations in adenomatous polyposis coli (APC), a key regulator of the pathway, and studied b-catenin expression and interactions with the expression of other markers of apoptosis, angiogenesis, and proliferation in patients with invasive urothelial cancer. The mutation cluster region of APC was directly sequenced in 70 patients with muscle invasive disease who were treated with surgery and adjuvant chemotherapy. COX-2, p53, Ki67, and b-catenin were studied immunohistochemically and micro vessel density was quantified by CD105 expression. Single somatic amino-acid substitutions (missense) were found in 9 (13%) and frameshift deletions in 2 (3%) tumors, all located in regions adjacent to b-catenin binding sites. Patients having either APC missense mutations or b-catenin nuclear accumulation had less frequent COX-2 overexpression (24% vs. 76%, p = 0.043) and more frequent lymph node involvement (75% vs. 38%, p = 0.023). Patients with either APC mutations or b-catenin accumulation had shorter disease-free interval (13.4 vs. 28 months, p = 0.07), whereas in multivariate analysis they had shorter disease-specific survival (60.5 vs. 20.6 months, p = 0.048). Somatic APC missense mutations are not rare in advanced urothelial neoplasms. Either APC mutations and/or aberrant expression of b-catenin are associated with worse outcome. Further study of the role of the Wnt pathway, potential crosstalk with other pathways and potential candidate therapeutic targets in urothelial cancer is needed. © 2008 Wiley-Liss, Inc. [source] Genetic polymorphism of sulfotransferase 1A1, cigarette smoking, hazardous chemical exposure and urothelial cancer risk in a Taiwanese populationINTERNATIONAL JOURNAL OF UROLOGY, Issue 12 2008Yuan-Hung Wang Objectives: To investigate the association between genetic polymorphism of sulfotransferase1A1 (SULT1A1), cigarette smoking, hazardous chemical exposure and urothelial cancer risk in a Taiwanese population. Methods: In a hospital-based case,control study, a total of 300 urothelial cancer (UC) cases and 300 cancer-free controls frequency-matched by age and gender were recruited from September 1998 to December 2005. The SULT1A1 arginine213histidine (Arg213His) polymorphism was genotyped using a polymerase chain reaction,restriction fragment length polymorphism method. Results: We found that the significantly increased UC risks of ever smokers and heavy smokers (,28 pack-years) were 2.1 (95% confidence interval [CI] = 1.4,3.3) and 2.2 (95% CI = 1.3,3.6), respectively. An increased UC risk of 1.8 (95% CI = 0.8,3.8) was observed among individuals with more than one item of hazardous chemical exposure, but it was not statistically significant. Compared with study subjects carrying the SULT1A1 Arg/Arg genotype, those with SULT1A1 Arg/His or His/His genotypes have a significantly decreased UC risk (Odds ratio [OR] = 0.5, 95% CI = 0.3,0.8). Heavy smokers carrying the SULT1A1 Arg/Arg genotype have a significantly increased UC risk (OR = 5.2, 95% CI = 2.3,11.6). Individuals who had been exposed to more than one item of hazardous chemicals and who carried the SULT1A1 Arg/Arg genotype have a significantly increased UC risk (OR = 3.7, 95% CI = 1.4,9.7). The highest significant increased UC risk (OR = 16.1, 95% CI = 2.9,87.2) was observed among ever smokers with hazardous chemical exposure and the SULT1A1 Arg/Arg genotype. Conclusions: SULT1A1 Arg213His polymorphism is associated with the development of UC, especially among cigarette smokers exposed to hazardous chemicals. [source] Pharmacokinetics of cisplatin and methotrexate after M-VAC chemotherapy for advanced urothelial cancer in hemodialysis patientsINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2008Kazuhiro Matsumoto md No abstract is available for this article. [source] Adjuvant methotrexate, vinblastine, adriamycin, and cisplatin chemotherapy has potential to prevent recurrence of bladder tumors after surgical removal of upper urinary tract transitional cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2008Norihito Soga Objectives: To evaluate the efficacy of adjuvant platinum based chemotherapy in upper urinary tract urothelial cancer following surgical resection in terms of survival benefit and inhibition of bladder cancer recurrence. Methods: Between April 1986 and August 2005, a total of 132 patients with a diagnosis of upper urinary tract urothelial cancer underwent radical nephroureterectomy with cuff of bladder at our department. A total of 46 patients (13 with pT2pN0M0 and 33 with pT3 pN0M0 transitional cell carcinoma without prior bladder cancer) were enrolled. Patients with locally advanced disease were divided into two groups: the adjuvant chemotherapy group (24 patients) who received adjuvant methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC) and the non-adjuvant chemotherapy group who did not receive adjuvant M-VAC (22 patients). Results: There were no statistically significant differences in patient characteristics or 10-year survival between the two groups. The recurrence rate in the non-adjuvant chemotherapy group was significantly higher than in the adjuvant chemotherapy group (log-rank test, P < 0.0001). Only non-adjuvant chemotherapy was a significant and independent risk factor (hazard ratio 6.97) for the development of intravesical recurrence (P < 0.01). Conclusion: Adjuvant M-VAC is an important optional adjuvant therapy and can prevent recurrent bladder tumors following surgery for upper urinary tract transitional cell carcinoma. To determine whether adjuvant chemotherapy has further benefit, a randomized study would be needed. [source] Origin of multifocal carcinomas of the bladder and upper urinary tract: Molecular analysis and clinical implicationsINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2005TOMONORI HABUCHI Abstract The simultaneous or metachronous development of multifocal tumors with identical or variable histological features in the urothelial tract in a single patient is a well-known characteristic of urothelial cancer. To explain this phenomenon, two distinct concepts have been proposed: the ,field defect' hypothesis according to which urothelial cells in patients are primed to undergo transformation by previous carcinogenic insults and the ,single progenitor cell' hypothesis, which asserts that the multifocal development is caused by the seeding or intraepithelial spread of transformed cells. Results of recent molecular genetic studies support the ,single progenitor cell' hypothesis, and indicate that the genetic and phenotypic diversity observed in multifocal urothelial tumors is a consequence of clonal evolution from a single transformed cell. An understanding of the mechanism of the heterotopic recurrence of urothelial cancer may provide new prospects for early molecular detection and prevention of heterotopic recurrence of urothelial cancer. [source] Impact of adjuvant systemic chemotherapy on postoperative survival in patients with high-risk urothelial cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2004SHIN SUZUKI Abstract Background:, The objective of this study was to retrospectively investigate the effectiveness of adjuvant combination chemotherapy for locally advanced urothelial cancer. Methods:, Between 1987 and 1998, 56 patients with locally advanced bladder (n = 27) or upper urinary tract (n = 29) cancer (pathological stage T3, T4 or N1, N2 and M0) were treated by radical cystectomy or radical nephroureterectomy and regional lymphadenectomy. Thirty-one patients had lymph node-positive disease and 25 patients did not. Twenty patients underwent adjuvant chemotherapy and 36 patients were observed after surgery. Cox proportional hazards models were used to determine the impact of numerous clinicopathological findings on survival. A subgroup analysis of patients with lymph node-positive disease was conducted to evaluate disease-free survival and overall survival rates. Results:, In this series, the median follow-up period was 39 months (range, 4,163) after surgery. Disease-free and overall survival rates of all 56 patients were 45% and 58%, respectively, at 3 years. Only lymph node status was significantly associated with disease-free and overall survival in the multivariate analyses. In a subgroup analysis of patients with lymph node-positive disease, 16 patients who underwent adjuvant chemotherapy had superior disease-free survival compared to 15 patients with no adjuvant chemotherapy (P = 0.0376). Conclusion:, These findings show that the prognosis of advanced urothelial cancer is significantly associated with nodal status. Furthermore, adjuvant combination chemotherapy has a positive impact on survival in patients with lymph node-positive disease. [source] Expression of CD44s and CD44v6 in transitional cell carcinomas of the urinary bladder: comparison with tumour grade, proliferative activity and p53 immunoreactivity of tumour cells,APMIS, Issue 11 2007JITKA KUNCOVÁ Alterations of CD44 glycoproteins have been shown to play an important role in progression of various malignancies, including urothelial cancer. We investigated expression patterns of CD44s and CD44v6 in transitional cell carcinoma (TCC) of the urinary bladder in relation to tumour grade, proliferative activity, and immunoreactivity for p53. The selected markers were detected immunohistochemically in 122 samples of TCC. We found a close relationship between CD44s and CD44v6 expression and tumour grade. The extension of positive staining for CD44s and CD44v6 towards the luminal surface was a predominant feature of differentiated carcinomas (grades 1 and 2), suggesting deranged maturation of cancer cells related to their neoplastic transformation. Heterogeneous expression of CD44s and CD44v6 predominated in poorly differentiated tumours (G3,4). However, areas of squamous differentiation within the high-grade tumours displayed strong immunoreactivity for both CD44s and CD44v6. The proliferative activity and p53 overexpression increased with the dedifferentiation of the tumour. The results of this study are discussed in relation to the significance of CD44 expression in TCC and to the explanation for controversial results reported in previous studies on the relationship between CD44 expression and the biological behaviour of urothelial cells. [source] Renal surgery in the elderly: morbidity in patients aged >75 years in a contemporary seriesBJU INTERNATIONAL, Issue 6 2008Michael Staehler OBJECTIVES To evaluate the surgical complications in a contemporary group of elderly patients with renal masses, as almost a quarter of patients with newly diagnosed renal mass are aged >74 years, with the potential for significant comorbidity. PATIENTS AND METHODS From April 2004 to June 2007, of 379 surgical resections of renal tumours, we assessed 117 consecutive patients aged ,75 years, who had either radical nephrectomy (RN) or partial nephrectomy (PN) for assumed renal cell carcinoma. Also elderly patients who had nephroureterectomy (NU) for upper urothelial cancer were followed. RESULTS Fifty patients had RN, 57 PN and 10 had NU; the median (range) age of all patients was 78.1 (72.7,92.5) years and was similar in all groups. No patient died during surgery and only one died within 90 days. The complication rates during and after surgery RN, PN and NU were 12%, 15% and 20%, respectively; the major complications within 30 days were 4%, 7% and 10%; major complications included bleeding during surgery and one acute bleeding event after surgery in the PN group. CONCLUSIONS Open renal surgery in elderly patients can be done safely; there was no difference in morbidity among RN, PN and NU. Renal surgery in the elderly patient is safe if done at a specialized centre. Mortality and morbidity can be very low, rendering this a feasible approach in the treatment of renal masses even if the prognosis is not determined by the oncological situation but by comorbidity. [source] Single-institution experience with primary tumours of the male urethraBJU INTERNATIONAL, Issue 8 2008Rolf Gillitzer OBJECTIVE To assess primary tumours of the urethra in males. PATIENTS AND METHODS We retrospectively reviewed our database from 1986 to 2006 for primary tumours of the male urethra; nine patients with primary tumours of the urethra were analysed and follow-up information was obtained. RESULTS Three patients had tumours of the prostatic urethra, two of which had proliferating focal inflammation and one a low-grade, superficial urothelial cancer. All patients were treated successfully with transurethral resection. Six patients had carcinoma of the bulbar or penile urethra, including two with previous local percutaneous radiotherapy for prostate cancer. All had primary surgical excision that was adapted to tumour location and extension. One patient had adjuvant chemotherapy after surgery. All but one patient remain recurrence-free after a median follow-up of 20 months. CONCLUSION Primary carcinoma of the male urethra is a rare entity. Previous radiotherapy might be a predisposing factor. Local surgical tumour control is essential for long-term survival, but the extent of surgery depends on tumour location and stage. Multimodal therapy might be required to obtain an optimum oncological outcome. [source] Socio-economic deprivation and survival in bladder cancerBJU INTERNATIONAL, Issue 4 2004Gulnaz Begum OBJECTIVES To investigate the relationship between deprivation, delay and survival from bladder cancer in the West Midlands, as socio-economic deprivation is associated with worse survival in many malignancies, and it has been suggested that treatment differences and delay in seeking care are major contributing causes. PATIENTS AND METHODS Data were prospectively collected on 1537 newly diagnosed cases of urothelial cancer presenting in the West Midlands between January 1991 and June 1992. Survival was censored at 31 July 2000, when 785 (51%) patients had died. The influence of deprivation on survival was explored using cause-specific and all-cause mortality. RESULTS Patients in less affluent groups had significantly worse survival than patients in more affluent groups when considering deaths from all causes (P = 0.02), which held true when adjusting for independent prognostic factors (age, smoking history, and tumour grade, stage, type and size). Bladder cancer-specific mortality showed no significant difference between socio-economic groups (P = 0.30). CONCLUSION Socio-economic deprivation is a significant predictor of survival when death from all causes is considered. However, this does not hold true for bladder cancer-specific death. The perceived differences in treatment and delay between socio-economic groups do not seem to occur for bladder cancer in the West Midlands. [source] Urinary markers for urothelial cancerBJU INTERNATIONAL, Issue 7 2004T.M. Lane First page of article [source] Treatment options for muscle-invasive urothelial cancer for patients who were not eligible for cystectomy or neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatinCANCER, Issue 10 2008Report of Southwest Oncology Group Trial 873 Abstract BACKGROUND. Many patients with invasive urothelial cell cancer are poor candidates for cisplatin-based chemotherapy, and many are high risk for cystectomy. Southwest Oncology Group Trial 8733 was designed to address treatment for such patients. METHODS. Eligible patients had primary or recurrent muscle-invasive disease with transitional cell or squamous cell histology, a performance status from 0 to 2, no extrapelvic disease, a life expectancy >3 months, and adequate hematologic function. The treating clinician assigned patients to operable or inoperable groups. All patients received 2 cycles of 5-fluorouracil (5-FU) at a dose of 1000mg/m2 per day × 4 starting concurrently with radiation at a dose of 200 centigrays per day × 10 each cycle. After 2 cycles, operable patients with positive biopsies underwent cystectomy, and patients with negative biopsies received a third cycle of chemoradiotherapy. Patients in the inoperable group received 3 cycles without interim biopsy. RESULTS. Eighteen of 24 eligible patients in the operable group were evaluable for response. Five patients had a complete response (CR), 9 patients had stable disease, 1 patient had progressive disease, and 3 patients were not assessable. The median progression-free survival was 10 months (95% confidence interval [95% CI], 4,14 months), and the median overall survival was 18 months (95% CI, 7,28 months). In the inoperable group, 35 of 37 eligible patients were evaluable for response with 17 CRs (49%; 95% CI, 31%,66%). The median progression-free survival was 13 months (95% CI, 10,17 months), and the median overall survival was 20 months (95% CI, 11,53 months). There were no episodes of grade 4 toxicity. CONCLUSIONS. In the current study, the combination of 5-FU and radiation was found to be tolerated well by patients with numerous comorbidities who could not tolerate cisplatin-based therapy or cystectomy. Cancer 2008. © 2008 American Cancer Society. [source] | ||||||||||||||||||||||