[Show abstract][Hide abstract] ABSTRACT: To develop two nomograms predicting disease-free survival (DFS) and cancer-specific survival (CSS) and to externally validate them in multiple series.
Prospectively collected data from a single-centre series of 818 consecutive patients who underwent RC and PLND were used to build the nomogram. External validation was performed in 3,173 patients from 7 centres worldwide. Time to recurrence and to cancer-specific death were addressed with univariable and multivariable analyses. Nomograms were built to predict 2-, 5- and 8-year DFS and CSS probabilities. Predictive accuracy was quantified using the concordance index.
Age, pathologic T stage, lymph-node density and extent of PLND were independent predictors of DFS and CSS (p < 0.05). Discrimination accuracies for DFS and CSS at 2, 5 and 8 years were 0.81, 0.8, 0.79 and 0.82, 0.81, 0.8, respectively, with a slight overestimation at calibration plots beyond 24 months. In the external series, predictive accuracies for DFS and CSS at 2, 5 and 8 years were 0.83, 0.82, 0.82 and 0.85, 0.85, 0.83 for European centres; 0.73, 0.72, 0.71 and 0.80, 0.74, 0.68 for African series; 0.76, 0.74, 0.71 and 0.79, 0.76, 0.73 for American series.
These nomograms developed from a contemporary series are simple clinical tools and provide optimal oncologic outcome prediction in all external cohorts.
World Journal of Urology 12/2014; 191(4). DOI:10.1007/s00345-014-1465-4 · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
and objectives: We evaluated the association of multiple biomarkers with clinical outcomes in patients treated with radical cystectomy (RC) for squamous cell carcinoma (SCC) of the bladder to identify the best prognostic panel of markers.
Immunohistochemistry for 14 biomarkers was performed on tissue microarray sections of 151 RC specimens with SCC. Biomarker alterations, pathological features as well as oncological outcomes were evaluated. The panel of biomarkers that best predicted oncological outcome was determined. Outcomes were stratified based on a prognostic score according to the number of altered biomarkers. The accuracy of oncological outcome prediction was evaluated by Receiver Operating Characteristic curve.
The study included 151 patients. Pathological stage was T2 in 50%, T3 in 38% and T1 and T4 in 6% of the patients. Median follow-up was 63.2 months. The best prognostic panel of markers included COX-2, FGF-2, p53, Bax and EGFR. A prognostic score (PS) based on marker alterations was an independent predictor of disease recurrence (intermediate risk: HR 3.2, and p=0. 008; high risk: HR 15.5 and p≤ 0.001) and bladder cancer-specific mortality (intermediate risk: HR 5.2, and p=0. 009; high risk: HR 19.4, and p≤ 0.001) in multivariable Cox regression analysis. A multivariable prognostic model incorporating PS demonstrated a significantly better performance in predicting outcome compared to clinicopathological parameters only (0.78 versus 0.64; respectively).
Biomarkers have significant potential to predict outcome after RC for SCC. An increased number of altered markers may identify high risk patients who might benefit from multimodal treatment approaches.
The Journal of Urology 09/2014; 193(2). DOI:10.1016/j.juro.2014.08.109 · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
To determine the incidence, risk factors and causes of hospital readmission in a large series of patients who underwent radical cystectomy (RC) and urinary diversion.Patients and Methods
We retrospectively analysed the data of 1000 patients who underwent RC and urinary diversion between January 2004 and September 2009 in our tertiary referral centre. Patients stayed in hospital for 21 and 11 days for orthotopic and ileal conduit diversions, respectively. The primary outcome was the development of a complication requiring hospital readmission at ≤3 months (early) and >3 months (late). Causes of hospital readmissions were categorised according to frequency of readmissions. Predictors were determined using univariate and multivariate logistic regression models.ResultsIn all, 895 patients were analysed excluding 105 patients because of perioperative mortality and loss to follow-up. Early and late readmissions occurred in 8.6% and 11% patients, respectively. The commonest causes of first readmission were upper urinary tract obstruction (UUO, 13%) and pyelonephritis (12.4%) followed by intestinal obstruction (11.9%) and metabolic acidosis (11.3%). The development of postoperative high-grade complications (odds ratio [OR] 1.955; 95% confidence interval [CI] 1.254-3.046; P = 0.003) and orthotopic bladder substitution (OR 1.585; 95% CI 1.095-2.295; P = 0.015) were independent predictors for overall hospital readmission after RC. Postoperative high-grade complications (OR 2.488; 95% CI 1.391-4.450; P = 0.002), orthotopic bladder substitution (OR 2.492; 95% CI 1.423-4.364; P = 0.001) and prolonged hospital stay (OR 1.964; 95% CI:1.166-3.308; P = 0.011) were independent predictors for early readmission while hypertension (OR 1.670; 95% CI 1.007-2.769; P = 0.047) was an independent predictor for late readmission.Conclusion
Hospital readmissions are a significant problem after RC. In the present study, UUO, pyelonephritis, metabolic acidosis and intestinal obstruction were the main causes of readmission. Orthotopic bladder substitution and development of postoperative high-grade complications were significant predictors for overall readmission.
BJU International 06/2014; 115(1). DOI:10.1111/bju.12830 · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The urinary reconstructive options available after radical cystectomy (RC) for bladder cancer are discussed, as are the criteria for selection of the most appropriate diversion, and the outcomes and complications associated with different diversion options.
To critically review the peer-reviewed literature on the function and oncological outcomes, complications, and factors influencing choice of procedure with urinary diversion after RC for bladder carcinoma.
A Medline search was conducted to identify original articles, review articles, and editorials on urinary diversion in patients treated with RC. Searches were limited to the English language. Keywords included: 'bladder cancer', 'cystectomy', 'diversion', 'neobladder', and 'conduit'. The articles with the highest level of evidence were selected and reviewed, with the consensus of all of the authors of this paper.
Both continent and incontinent diversions are available for urinary reconstruction after RC. In appropriately selected patients, an orthotopic neobladder permits the elimination of an external stoma and preservation of body image without compromising cancer control. However, the patient must be fully educated and committed to the labour-intensive rehabilitation process. He must also be able to perform self-catheterisation if necessary. When involvement of the urinary outflow tract by tumour prevents the use of an orthotopic neobladder, a continent cutaneous reservoir may still offer the opportunity for continence albeit one that requires obligate self-catheterisation. For patients who are not candidates for continent diversion, the ileal loop remains an acceptable and reliable option.
Both continent and incontinent diversions are available for urinary reconstruction after RC. Orthotopic neobladders optimally preserve body image, while continent cutaneous diversions represent a reasonable alternative. Ileal conduits represent the fastest, easiest, least complication-prone, and most commonly performed urinary diversion.
BJU International 01/2014; 113(1):11-23. DOI:10.1111/bju.12121 · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: To assess the effect of internal ureteral stents (IUS) on renal function (RF) and to determine factors associated with the RF changes. Methods: Between February 2009 and September 2012, 103 patients with bilateral or IUS in a solitary kidney were retrospectively analyzed. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI). It was calculated from serum creatinine after adequate relief of obstruction (baseline) and at last follow-up. Deterioration of eGFR was considered if last eGFR declined by >20% from the baseline value. Predictors of RF changes were detected using univariate and multivariate binary logistic regression analyses. Results: The mean patients' age was 54 + 14 years with males constituting 71.4% of study population. During follow-up after IUS fixation, the median eGFR has declined from 50.6 ml/min/1.73m2 at baseline to 25 ml/min/1.73m2 at time of last follow-up (p<0.0001). Fifty two (50.5%) patients experienced decline in their RF by >20% of baseline value. On multivariate analysis, positive urine culture (OR: 3; p=0.026), baseline eGFR <60 ml/min (OR: 3.6; p=0.011) and extraluminal obstruction (OR: 2.9; p=0.035) were independent predictors of RF deterioration. Conclusions: One half of patients with IUS lasting more than 3 months experienced RF deterioration during follow-up. This decline was significantly associated with positive urine cultures, presence of CKD and extraluminal obstruction. All efforts should be exerted for active treatment of associated urinary tract infection and active follow-up of RF.
Journal of endourology / Endourological Society 09/2013; DOI:10.1089/end.2013.0521 · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study was designed to determine the possible impact of hepatitis C virus (HCV) infection on the expression of telomerase (TERT), retinoblastoma (RB1), E2F3, TP53, CDKN1A (p21) and fibroblast growth factor receptor- 3 (FGFR3) genes in patients with bladder cancer (BC).Materials and methods100 patients with bladder cancer (15 female and 85 male) were divided into 2 groups; Group I: 50 HCV negative subjects (age range 36--79), and Group II: 50 HCV positive subjects (age range 42--80). Expressions of the telomerase, retinoblastoma (Rb), E2F3, TP53 and FGFR3 genes were tested by immunohistochemistry and real time PCR in tumour tissues and healthy bladder tissues. Also, telomerase activity was assessed by telomeric repeats amplification protocol (TRAP).
Bladder tumors associated with HCV infection were of high grade and invasive squamous cell carcinomas (SCCs). Expressions of hTERT, Rb, E2F3, TP53 and FGFR3 as well as telomerase activity were significantly higher in bladder tissues of HCV-infected patients compared with bladder tissues of non infected patients (p<0.05). On the contrary, CDKN1A (p21) expression was significantly lower in bladder tissues of HCV-infected patients compared to bladder tissues of non infected patients (p<0.05).
The expressions of hTERT, Rb, E2F3, TP53 and FGFR3 as well as the activity of telomerase were significantly high in malignant bladder tissues associated with HCV infection. On the other hand, CDKN1A (p21) expression was low in bladder tissues of HCV-infected subjects. Moreover, there was a positive correlation between HCV infection and expression of telomerase, E2F3, TP53 and FGFR3. There was a negative correlation between HCV infection and expression of Rb and p21.
Infectious Agents and Cancer 06/2013; 8(1):24. DOI:10.1186/1750-9378-8-24 · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background A high serum level of female protein (FP), found to be a constituent of Syrian hamster amyloid was associated with enhanced amyloidosis. In this work, we studied the
sex-limited factors in the induction of amyloidosis in Syrian hamsters infected with either Schistosoma mansoni or S. hematobium cercariae. Methods Hamsters were infected with different species of schistosome cercariae and sacrificed after different time periods of infection. Kidney and liver specimens were processed in paraffin, stained with Congo-red and examined by ordinary light and polarized light microscopy. Results Statistical analysis showed a significant difference in intensity of kidney and liver amyloid deposits (P< 0.002 and < 0.007, respectively) between females and male hamsters with extensive deposits in the former. Amyloid deposits were correlated significantly to the duration of infection (P < 0.001) than the worm load recovered. Conclusion We conclude that, in a hamster model, Schistosoma-induced amyloidosis is enhanced in female compared to male hamsters. This may be due to the high serum level of FP that is normally detected in females. As an experimental model for schistosomal nephropathy, we recommend to use male hamsters instead of females to minimize the effect of amyloid deposits, which may mask other pathological changes associated with schistosomal infection.
[Show abstract][Hide abstract] ABSTRACT: Background:
The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer.
The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry.
We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients.
These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.
British Journal of Cancer 01/2013; 108(4). DOI:10.1038/bjc.2012.573 · 4.82 Impact Factor