Impact of the use of bowel for urinary diversion on perioperative complications and 90-day mortality in patients aged 75 years or older.

OBJECTIVE: A potential strategy to decrease the high complication rate of radical cystectomy (RC) in the elderly is to avoid the use of bowel for urinary diversion. The aim of this study was to address this issue in a multicentre study of patients aged ≥ 75 years. PATIENTS AND METHODS: We performed a retrospective, multicentre study of a consecutive series of patients aged ≥ 75 years who underwent RC for muscle-invasive bladder cancer between 2006 and 2010. Medical, surgical and wound complications were graded according to the modified Clavien-Dindo classification. RESULTS: A total of 256 patients (68% men, mean age 79.6 years) were analysed. 204 (80%) patients received a urinary diversion with use of bowel and 52 (20%) a ureterocutaneostomy (UC). Patients with UC were older (82.0 vs. 78.9 years, p < 0.001) and had a higher ASA score (2.6 vs. 2.3, p = 0.007), while the mean Charlson score was lower (4.2 vs. 5.6, p < 0.001). Patients with UC had a shorter operating time (279 vs. 311 min, p = 0.002) and a shorter period in the intensive care unit (0.9 vs. 2.2 days). The overall rate of severe complications graded as Clavien III-V was significantly lower in the UC group (11.5%) as compared to patients receiving bowel for urinary diversion (25.0%) (p = 0.003). Severe (Clavien grade III-V) medical (3.9 vs. 10.3%) and surgical (2.1 vs. 14.1%) complications were all less frequent in the UC group. Inpatient, 30- and 90-day mortality was 5.8, 7.7 and 17.3% in the UC group as compared to 3.9, 5.9 and 6.9% in the bowel cohort, respectively. CONCLUSION: UC following RC is associated with a lower complication rate in geriatric patients. The constantly increasing cohort of geriatric, multimorbid patients requiring cystectomy might justify reconsideration of this form of diversion.

Bladder cancer--the neglected tumor: a descriptive analysis of publications referenced in MEDLINE and data from the register ClinicalTrials.gov.

BACKGROUND: Uro-oncological neoplasms have both a high incidence and mortality rate and are therefore a major public health problem. The aim of this study was to evaluate research activity in uro-oncology over the last decade. METHODS: We searched MEDLINE and ClinicalTrials.gov systematically for studies on prostatic, urinary bladder, kidney, and testicular neoplasms. The increase in newly published reports per year was analyzed using linear regression. The results are presented with 95% confidence intervals, and a p value <0.05 was considered statistically significant. RESULTS: The number of new publications per year increased significantly for prostatic, kidney and urinary bladder neoplasms (all <0.0001). We identified 1,885 randomized controlled trials (RCTs); also for RCTs, the number of newly published reports increased significantly for prostatic (p = 0.001) and kidney cancer (p = 0.005), but not for bladder (p = 0.09) or testicular (p = 0.44) neoplasms. We identified 3,114 registered uro-oncological studies in ClinicalTrials.gov. However, 85% of these studies are focusing on prostatic (45%) and kidney neoplasms (40%), whereas only 11% were registered for bladder cancers. CONCLUSIONS: While the number of publications on uro-oncologic research rises yearly for prostatic and kidney neoplasms, urothelial carcinomas of the bladder seem to be neglected despite their important clinical role. Clinical research on neoplasms of the urothelial bladder must be explicitly addressed and supported.

Quadrimodal treatment of high-risk T1 and T2 bladder cancer: transurethral tumor resection followed by concurrent radiochemotherapy and regional deep hyperthermia.

BACKGROUND AND PURPOSE: To assess the safety and effectiveness of treating high-risk T1 and T2 bladder cancer with transurethral resection (TUR-BT) followed by radiochemotherapy (RCT) combined with regional deep hyperthermia (RHT). MATERIAL AND METHODS: Between 2003 and 2007, 45 patients were enrolled. After TUR-BT patients received radiotherapy (RT) of the bladder and regional lymph nodes with 50.4 Gy, and a boost to the bladder of 5.4-9 Gy. RCT was applied to 43/45 patients. RHT was administered once weekly. Response was re-evaluated 6 weeks after RT by restaging-TUR. Toxicity was graded with the CTCAE, version 3.0. QoL was evaluated by a dedicated questionnaire. RESULTS: The median follow-up was 34 months (range 12-60). The median number of hyperthermia treatments was 5 (range 1-7). Acute toxicity grades 3 and 4 occurred in 20% (9/45) and 9% (4/45), respectively. Late toxicity grades 3/4 were seen in 24% (11/45). Complete response rate was 96% (43/45). Local recurrence-free survival was 85%, overall survival was 80%, disease-specific survival was 88%, metastasis-free survival was 89%, and the bladder-preserving rate was 96% (43/45) at 3 years. Eighty percent (24/30) were at least mostly satisfied with their bladder function. CONCLUSIONS: The quadrimodal treatment was feasible and well tolerated. Local control and bladder-preserving rates were encouraging.

Survivin expression as a predictive marker for local control in patients with high-risk T1 bladder cancer treated with transurethral resection and radiochemotherapy.

PURPOSE: The objectives of this study were to investigate the expression of survivin in tumor samples from patients with high-risk T1 bladder cancer and to correlate its expression with clinicopathologic features as well as clinical outcomes after initial transurethral resection (TURBT) followed by radiotherapy (RT) or radiochemotherapy (RCT). METHODS AND MATERIALS: Survivin protein expression was evaluated by immunohistochemistry on tumor specimen (n = 48) from the initial TURBT, and was correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure, tumor progression, and death from urothelial cancer after primary bladder sparring treatment with RT/RCT. RESULTS: Survivin was not expressed in normal bladder urothelium but was overexpressed in 67% of T1 tumors. No association between survivin expression and clinicopathologic factors (age, gender, grading, multifocality, associated carcinoma in situ) could be shown. With a median follow-up of 27 months (range, 3-140 months), elevated survivin expression was significantly associated with an increased probability of local failure after TURBT and RCT/RT (p = 0.003). There was also a clear trend toward a higher risk of tumor progression (p = 0.07) and lower disease-specific survival (p = 0.10). CONCLUSIONS: High survivin expression is a marker of tumor aggressiveness and may help to identify a subgroup of patients with T1 bladder cancer at a high risk for recurrence when treated with primary organ-sparing approaches such as TURBT and RCT.

Treatment options for high-risk T1 bladder cancer: status quo and future perspectives of radiochemotherapy.

PURPOSE: To review the standards and new developments in diagnosis and management of high-risk T1 bladder cancer with emphasis on the role of radiotherapy (RT) and radiochemotherapy (RCT). MATERIAL AND METHODS: A systematic review of the literature on developments in diagnosis and management of high-risk T1 bladder cancer was performed. RESULTS: First transurethral resection (TUR), as radical as safely possible, supported by fluorescence cystoscopy, shows higher detection and decreased recurrence rates. An immediate single postoperative instillation with a chemotherapeutic drug reduces the relative risk of recurrence by 40%. A second TUR is recommended to assess residual tumor. For adjuvant intravesical therapy, bacille Calmette-Guérin (BCG) demonstrated the highest efficacy. Early cystectomy should be reserved for selected patients. A recent phase III trial comparing RT versus conservative treatment in T1 G3 tumors could not show any advantage for RT. Data from Erlangen, Germany, using combined RCT in 80% of the patients, compare favorably with most of the contemporary BCG series. CONCLUSION: Results of intravesical therapy are still unsatisfying and early cystectomy is associated with morbidity and mortality. RT alone proved not superior to other conservative treatment strategies. However, data on RCT are promising and demonstrate an alternative to intravesical therapy and radical cystectomy.

Polymorphisms in the human progesterone receptor (PGR) gene of two human prostate adenocarcinoma cell lines.

BACKGROUND: The incidence and mortality rate of prostate cancer has been steadily increasing in most countries worldwide. A potential implication of the progesterone receptor has been reported in prostatic carcinogenesis. In this study, an allele of human progesterone receptor gene (PROGINS), which was demonstrated to be associated with an increased risk of sporadic ovarian cancer, was tested in two human prostate cancer cell lines, PC-EW and PC-OR. MATERIALS AND METHODS: Genomic DNA was isolated from the cell lines in athymic nude mice. The polymorphisms in exon 4 and exon 5 and the insertion in intron G (PROGINS) were identified by sequencing and gel electrophoresis. RESULTS: The PROGINS allele and the polymorphisms in exon 4 and exon 5 were found heterozygous in the PC-OR cell line but not in the PC-EW cell line. CONCLUSION: We described the polymorphisms of exon 4, exon 5 and PROGINS in prostate cancer. Mutation screening of the PGR gene may provide information for risk assessment of developing prostate cancer.