Lymphadenectomy before and after radical cystectomy: does this affect the radicality? A prospective randomized comparative study.

PURPOSE: To compare the oncological outcome of performing ePLND before or after RC in 200 patients in a prospective randomized manner. MATERIALS AND METHODS: From January 2014 to December 2019, 200 patients with T2-T3b N0M0 BCa were included in the current study after signing an informed consent. Patients were divided into two groups, 100 in each one. Group I underwent ePLND before RC, whereas group II underwent ePLND after RC. Postoperative evaluation included clinical, laboratory, and radiographic studies. RESULTS: Patients' characteristics were comparable between both groups. The mean operative time excluding that of urinary diversion was significantly shorter in group II than in group I (p = 0.01). The mean number of LNs removed was 25 ± 6 in group I and 32 ± 8 in group II (p = 0.141). Intraoperative complications occurred in four patients in the form of external iliac artery and vein injury [two in each group (p = 0. 245)]. Postoperative complications were comparable between both groups with no statistically significant difference (p = 0.375). Oncological failure occurred in 28 patients [16 (17.6%) in group I and 12 (22%) in group II (p = 0.389)]. CONCLUSIONS: EPLND before and after RC has comparable oncological outcomes. The stage of the disease, the time since the first diagnosis till RC and the surgeon experience in performing meticulous ePLND are more important. In absence of oncological superiority, the timing of ePLND should be judged according to the patient-related factors to facilitate safe RC with minimal morbidity.

Functional evaluation of a spiral neobladder with an angled chimney; A prospective randomized comparative study.

OBJECTIVES: to assess the functional outcome of performing ureteric re-implantation to an angled short chimney in a modified spiral orthotopic ileal neobladder. PATIENTS AND METHODS: From January 2018 to December 2020, 90 male patients with bladder cancer underwent radical cystectomy and spiral ileal neobladder reconstruction with a chimney. Patients were randomly divided in two groups according to the position of the chimney [straight and angled] to which the ureters will be implanted. Postoperative evaluation included clinical, laboratory, radiographic and urodynamic studies. RESULTS: There were no perioperative deaths. The mean operative time for the procedure was 4.7 ± 1.2 h in group I and 4.9 ± 1.3 h in group II (p 0.456). No intraoperative complications occurred. Early postoperative complications occurred in 8 patients. In group I, according to the modified Clavien system, GII complication occurred in 2 (5%) patients in the form of DVT in 1 (2.5%) and surgical site infection in 1 (2.5%). GIIIa occurred in 3 (7.5%) patients in the form of wound dehiscence. In group II, GII occurred in 2 (4.8%) patients in the form of prolonged urinary leakage and myocardial infarction, each occurred in one patient. GIIIb occurred in 1 (2.4%) patient in the form of intestinal leak. Poucho-ureteral reflux occurred in 10 patients [3 (7.5%) in group I and 7 (16.8%) in group II (p 0.001)]. CONCLUSIONS: The preliminary results of the right sided angled chimney during neobladder reconstruction are safe, acceptable, without an extra time to develop an anti-reflux technique and without an increased incidence of reflux.

Can Bcl-XL expression predict the radio sensitivity of bilharzial-related squamous bladder carcinoma? A prospective comparative study.

BACKGROUND: Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL. METHODS: The study prospectively included 71 patients, (47 males, 24 females) with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0) who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1), while 33 patients did not receive adjuvant radiotherapy (group 2). Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded. RESULTS: The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03). The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4-102.3, p < 0.0001) and radiotherapy (odd ratio 0.19, 95% CI 0.05-0.78, p < 0.02). With Cox regression, the only independent multivariate predictor of radio-sensitivity was the Bcl-XL expression with odd ratio 4.6 and a p value < 0.0001. All patients tolerated the treatment with no life threatening or late complications during the period of follow up. CONCLUSIONS: Adjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.

Does visceral peritoneal closure affect post-cesarean urinary symptoms? A randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: We hypothesized that upward bladder traction by visceral peritoneal closure during cesarean sections may have an impact on postpartum urinary complaints. METHODS: Based on a 90% power of the study and a 95% confidence interval, a sample size of 114 patients in each arm was needed to detect a 15% difference between both groups regarding postpartum urinary incontinence. To account for follow-up losses, we prospectively randomized 620 term primigravidas undergoing non-emergency cesareans into two groups (310 each): group 1, visceral peritoneal closure; group 2, non-closure. We compared perineal ultrasound findings 30 min before and 48 h after surgery. The UDI-6 questionnaire was used to assess urinary complaints. RESULTS: Group 1 showed significant widening of the posterior urethrovesical angle and alpha angle, more urethral descent 48 h postpartum and higher incidence of frequency, urge and stress incontinence 8 weeks postpartum. Symptoms disappeared almost completely after 6 months. CONCLUSIONS: Compared to visceral peritoneal non-closure, cesarean with visceral closure is associated with significant postpartum frequency of urination and/or incontinence that disappear without treatment almost completely within 6 months.

A Simple Immunohistochemical Panel Could Predict and Correlate to Clinicopathologic and Molecular Subgroups of Urinary Bladder Urothelial Carcinoma.

BACKGROUND: Although gene expression profiling provided a comprehensive molecular characterization of different subtypes of bladder urothelial carcinoma (UC), which are distinct in their biological features and prognosis, such a system is not yet applicable for routine clinical practice. This study aimed to examine the expression of these molecular classes of UC using simple panel of immunohistochemical markers. MATERIALS AND METHODS: Tissue sections from 192 specimens of UC were stained with FGFR3, CK5, CCNB1, HER-2, and P53. The molecular classes identified were correlated with clinicopathologic characteristics and patient survival. RESULTS: The most frequent class in our cohort was urobasal B (UroB) (44.1%), followed by squamous cell carcinoma-like (SCCL) (22%), genomically unstable (GU) (20.3%), and urobasal A (UroA) (13.6%). Patients with SCCL were significantly younger (P < .0001). Both the SCCL and GU types were of significantly higher histopathologic grade (P < .0001). UroA tumors were mainly of the T1 stage (75%), whereas 61.5% of the SCCL and 58.3% of the GU types were of stage T2 (P < .001). Prognosis was significantly different among groups. The SCCL class showed the lowest overall survival (38.5%; P = .030) and metastasis-free survival (69.2%; P = .017). The best prognosis was for UroA, with an overall survival of 75% and no metastatic events. CONCLUSION: The distribution of UC subtypes in our study was uniquely different from other studies. This simple immunohistochemical panel could be suggested as a clinically applicable tool that has the potential to be used routinely in guiding individualized treatment of UC.

Muscle invasive bladder cancer in Upper Egypt: the shift in risk factors and tumor characteristics.

BACKGROUND: In Egypt, where bilharziasis is endemic, bladder cancer is the commonest cancer in males and the 2nd in females; squamous cell carcinoma (SCC) is the commonest type found, with a peculiar mode of presentation. The aim of this study is to identify and rank the risk factors of muscle invasive bladder cancer (MIBC) in Upper Egypt and describe its specific criteria of presentation and histopathology. METHODS: This is an analytical, hospital based, case controlled study conducted in south Egypt cancer institute through comparing MIBC cases (n = 130) with age, sex and residence matched controls (n = 260) for the presence of risk factors of MIBC. Data was collected by personal interview using a well designed questionnaire. Patients' records were reviewed for histopathology and Radiologic findings. RESULTS: The risk factors of MIBC were positive family history [Adjusted odds ratio (AOR) = 7.7], exposure to pesticides [AOR = 6.2], bladder stones [AOR = 5], consanguinity [AOR = 3.9], recurrent cystitis [AOR = 3.1], bilharziasis [odds ratio (OR) = 5.8] and smoking [OR = 5.3]. SCC represented 67.6% of cases with burning micturition being the presenting symptom in 73.8%. CONCLUSION: MIBC in Upper Egypt is usually of the SCC type (although its percentage is decreasing), occurs at a younger age and presents with burning micturition rather than hematuria. Unlike the common belief, positive family history, parents' consanguinity, exposure to pesticides and chronic cystitis seem to play now more important roles than bilharziasis and smoking in the development of this disease in this area.

Correction to: Genetic aberrations of the K-ras proto-oncogene in bladder cancer in relation to pesticide exposure.

The original publication of this paper contains a mistake. Line 6 in the abstract, line should read "One hundred patients were diagnosed with bladder cancer and two hundred controls attended the outpatient clinic;"

Genetic aberrations of the K-ras proto-oncogene in bladder cancer in relation to pesticide exposure.

In Egypt, bladder cancer is one of the most popular cancers, accounting for 31% of all cancer cases. It ranks first in males about 16.2% of male cancer. The incidence in rural areas among males is near 32 per 100,000. The exact etiology of bladder cancer is still unknown; K-ras gene is known as a critical DNA target for chemical carcinogens such as pesticide. Some occupational hazard exposure is thought to be directly genotoxic, while others might enhance the mutagenicity and carcinogenicity of directly acting genotoxic agents. Analysis of the relationship between pesticide exposure and mutation in the K-ras gene in human bladder cancer. One hundred patients were diagnosed with bladder cancer and two hundred controls attended the outpatient clinic; after taking consent and filling a questionnaire for age, sex, occupation and pesticide exposure, surgically resected specimens were collected and the samples were used to determine the k-ras mutation. Blood samples were taken to analyze the level of acetylcholinesterase enzyme and level of P53. The present study indicated that pesticide exposure may play a great role in malignant transformation of the bladder cells through mutation in the K-ras gene; there was a significant correlation between the acetylcholinesterase enzyme level and k-ras mutation (p < 0.001). The results revealed that the level of P53 was significantly high in comparison with the control group (p < 0.001). These findings give an alarm to decrease the amount of pesticides used in our area; also, p53 may be used as an indicator to bladder cancer.

Primary versus deferred ureteroscopy for management of calculus anuria: a prospective randomized study.

INTRODUCTION: Obstructive anuria can be managed by primary ureteroscopy (URS) or deferred URS after initial ureteral stenting. We want to compare the primary URS and deferred URS in the management of calculus anuria regarding the feasibility and clinical outcome. MATERIAL AND METHODS: Between January 2012 and December 2014, 150 patients with anuria due to ureteral calculi were prospectively randomized according to the timing of ureteroscopic intervention into two groups; deferred URS group (69 patients who were treated initially by ureteral stenting) and primary URS group (81 patients who were treated by emergency URS). Follow-up was at least 6 months postoperatively. RESULTS: Complete stone clearance was 87 % and 75.3% for deferred and primary URS groups, respectively (p = 0.097). Renal function normalized in 94.2% of deferred URS vs. 97.5% of primary URS (p = 0.414). Deferred URS group had a 2.9 % overall complication rate in comparison to 9.9 % for the primary URS group (p = 0.109). Ureteral perforation/pyelonephritis was noted in 6.2% of the primary URS group only (p = 0.043). The median number of maneuvers required until stone clearance was one (range 1-5) for primary URS vs. two (range 2-3) for deferred URS (p <0.001). The cost of primary URS was significantly less (p <0.001). On a multivariate analysis, lower ureteral calculi (OR 13.03, 95% CI 4.07- 41.7, p <0.001) and deferred URS (OR 2.84, 95% CI 1.07-7.49, p = 0.035) were independent predictors for an eventless and successful URS. CONCLUSIONS: Primary URS for calculus anuria is feasible and cost-effective. It has a short hospital stay, but is still technically demanding. The perioperative complications are comparable to URS in normouric patients.

Does the site of the orthotopic neobladder outlet matter? A prospective randomized comparative study.

BACKGROUND: To compare the results of urethral anastomosis to a button hole and to the lowest part of the anterior suture line during orthotopic neobladder substitution. METHODS: From January 2012 to December 2015, 87 consecutive male patients with invasive bladder cancer underwent radical cystectomy and Hautmann ileal neobladder. Patients were randomly divided into two groups; group I (44 patients), the outlet was created as a button-hole at the most dependent part of the pouch, group II (43 patients), the lowest 1 cm of the anterior suture line of the pouch was left open as an outlet. Patients were randomly assigned to either group using computer-generated random numbers (JMP, Version 12.0.1; SAS Institute, Cary, NC, USA) via a sealed envelope. The functional outcomes of both groups were compared especially at the urethro-enteric anastomosis. RESULTS: There were no intraoperative complications. Early postoperative complications occurred in 9 patients (5 in group I and 4 in group II, p = 0.484). Prolonged urinary leakage persisted for 11 and 14 days in 2 patients in group I and 10 and 16 days in 2 patients in group II. Delayed postoperative complications occurred in 11 patients (5 [12.5%] in group I and 6 [15.6%] in group II) (p = 0.711). Three patients developed urethro-enteric strictures (2 in group I and 1 in group II) (p = 0.571). CONCLUSION: The "non-hole" technique of urethral anastomosis was not associated with a significant increase in the complication rate when compared to the commonly performed "hole" technique.

Diffusion weighted magnetic resonance imaging in bladder cancer, is it time to replace biopsy?

INTRODUCTION: To assess if the apparent diffusion coefficient (ADC) value of magnetic resonance imaging (MRI) can discriminate between the cell type, histological grade and improve staging of urinary bladder cancer (BC). MATERIAL AND METHODS: 102 patients with urinary bladder masses underwent MRI using a 1.5 T machine. T2 weighted and diffusion weighted imaging (DWI) using b values of 0, 150, 500 and 1000 s/mm2 were done. The ADC values of bladder masses were measured. These values were correlated with the histopathologic results. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of T2WI, DWI and T2WI plus DWI for detecting bladder lesions were evaluated. RESULTS: The cut-off ADC value for diagnosing malignant bladder wall pathologies was ≤1 x 10-3 mm2/s with 94.5% sensitivity and 87.5% specificity. The mean ADC value of different malignant cell types was statistically insignificant. A significant difference in ADC values was found between G1 and G3 (P = 0.000), G2 and G3 (P = 0.045) but not between G1 and G2 (p = 0.066). Staging accuracy for differentiation between invasive and non-invasive lesions was nearly the same for all MRI data sets. For differentiation between organ confined (pT1-pT2) and non-organ confined lesions (pT3-pT4), staging accuracy was better in T2WI plus DWI (83%) as compared to DWI alone (77%) or T2WI alone (75%). CONCLUSIONS: Adding DWI and the ADC value to T2WI improve the accuracy of MRI in BC detection and staging. However, at this time point, MRI cannot replace transurethral resection (TUR) biopsy or distinguish sharply between all different histologic grades and cell types.

Management of neobladder complications: endoscopy comes first.

OBJECTIVE: The aim of this study was to report the functional outcome after endoscopic management of neobladder complications. MATERIALS AND METHODS: Out of 197 patients who underwent radical cystectomy and orthotopic ileal neobladder reconstruction between 2007 and 2013, 30 patients with delayed postoperative complications were enrolled in this study. Complications were in the form of: eight patients with outflow obstruction, 12 with ureteroenteric stricture, nine with neobladder calculi and one with an isolated recurrent papillary tumor inside the neobladder. Patients were followed up regularly to assess the outcomes of endoscopic treatment. RESULTS: The mean maximum flow rate and postvoiding residual urine after endoscopic treatment of outflow obstruction were 18.2 ± 3.9 ml/s and 28.7 ± 11 ml, respectively. Ten patients with ureteroenteric stricture showed resolution of hydronephrosis after antegrade dilatation and JJ-stent fixation, with two patients requiring open surgery owing to impassable strictures. Complete clearance of neobladder calculi occurred after endoscopic neocystolithotripsy, with two patients requiring two sessions owing to large calculi. Transurethral resection of the neobladder for isolated tumor recurrence was performed in one patient over two sessions, followed by adjuvant chemoirradiation. CONCLUSIONS: Endourological management of orthotopic neobladder problems is the safest choice. It avoids the difficulties and complications of open surgery and has durable results.

Acridine Orange and Flow Cytometry: Which Is Better to Measure the Effect of Varicocele on Sperm DNA Integrity?

We evaluated the effect of varicocelectomy on semen parameters and levels of sperm DNA damage in infertile men. A total of 75 infertile men with varicocele and 40 fertile men (controls) were included in this study. Semen analysis and sperm DNA damage expressed as the DNA fragmentation index using acridine orange staining and chromatin condensation test by flow cytometry were assessed before and 6 months after varicocelectomy. The patients were also followed up for 1 year for pregnancy outcome. Semen parameters were significantly lower in varicocele patients compared to controls (P < 0.05). Mean percentages of sperm DNA fragmentation and sperm DNA chromatin condensation in patients were significantly higher than those in controls (P < 0.05). After varicocelectomy, sperm DNA fragmentation improved significantly, whereas sperm chromatin condensation was not significantly changed. In 15 out of 75 varicocele patients, clinical pregnancy was diagnosed; those with positive pregnancy outcome had significant improvement in sperm count, progressive sperm motility, and sperm DNA fragmentation, but there was no significant difference in sperm DNA condensation compared to negative pregnancy outcome patients. We concluded from this study that acridine orange stain is more reliable method than flow cytometry in the evaluation of sperm DNA integrity after varicocelectomy.

Percutaneous suprapubic stone extraction for posterior urethral stones in children: efficacy and safety.

OBJECTIVE: To evaluate the safety and efficacy of percutaneous suprapubic stone extraction (PSPSE) for pediatric posterior urethral stones. METHODS: Between July 2007 and June 2010, 54 boys presenting with acute urinary retention due to posterior urethral stones underwent PSPSE. Patients were a mean age of 66.4 months (range, 8-180 months). The stone size was 0.7-1.9 cm. Patients were placed under general anesthesia, and a 7F urethroscope was used to pushback the stone to the bladder. A 3-mm suprapubic puncture with a scalpel was performed, followed by insertion of a straight narrow hemostat through the puncture aided with cystoscopic guidance. The stone was grasped with the hemostat in its narrowest diameter and was extracted percutaneously or crushed if friable. The suprapubic puncture was closed with a single 4-0 Vicryl (Ethicon) suture. RESULTS: Intact stone retrieval was achieved in 45 patients, and the stone was crushed into minute fragments in 9 patients. Intraperitoneal extravasation developed in 1 patient that required open surgical intervention. Mean operative time was 22 minutes. Patients were monitored for up to 17 months, with complete resolution of symptoms and stone clearance. CONCLUSION: PSPSE provides a minimally invasive approach for the extraction of urethral and bladder stones in the pediatric population. The use of a straight hemostat for suprapubic stone extraction or crushing is a good alternative to suprapubic tract dilation, with minimal morbidity.

Comparing non contrast computerized tomography criteria versus dual X-ray absorptiometry as predictors of radio-opaque upper urinary tract stone fragmentation after electromagnetic shockwave lithotripsy.

The objective of this study was to assess the value of dual X-ray absorptiometry (DXA) in comparison to non contrast computed tomography (NCCT) density as possible predictors of upper urinary tract stone disintegration by shock wave lithotripsy (SWL). This study included 100 consecutive patients, with solitary renal stone 0.5-2 cm or upper ureteral stone up to 1 cm. DXA to calculate stone mineral density (SMD) and stone mineral content (SMC) was done. NCCT was performed to measure Hounsfield units (HU). SWL was performed with an electromagnetic lithotripsy, plain X-ray documented disintegration after SWL. Successful treatment was defined as stone free or complete fragmentation after 1 or 2 sessions of SWL. The impact of patients age, sex, body mass index, stone laterality, location, volume, length, mean SMC and SMD, HU and Hounsfield density (HD), skin to stone distance (SSD) and number of shock waves were evaluated by univariate and multivariate analysis. Only 76 patients were available for follow-up. Success of disintegration was observed in 50 out of 76 patients (65.8 %). On multivariate analysis, SMC and number of shock wave were the significant independent factors affecting SWL outcome (p = 0.04 and p = 0.000, respectively). SMC as detected by DXA is a significant predictor of success of stone disintegration by SWL. SMC measured by DXA is more accurate than HU measured by CT. Patients with high stone mineral content (SMC greater than 0.65 g) should be directly offered another treatment option.

Prepuce preserving versus conventional Mathieu urethroplasty for distal hypospadias - a prospective randomized study.

OBJECTIVES: To evaluate the impact of prepuce preservation during Mathieu repair for distal hypospadias. METHODS: This prospective randomized comparative study, carried out in Assiut University Hospital, between 2006 and 2009, included 200 patients with distal penile or coronal hypospadias. They underwent either Mathieu repair with prepuce preservation (group I, n = 100) or traditional Mathieu repair with circumcision (group II, n = 100). Follow up was at 2 weeks, and 1 and 3 months postoperatively, which only 153 patients completed (I: n = 86 and II: n = 67). RESULTS: The mean operative time was 64.5 min in group I and 121.7 min in group II (p < 0.001). All patients in group I developed postoperative preputial edema. Patients from group I who had a successful operation underwent circumcision at least 3 months later. Urethrocutaneous fistulae developed in 7 and 6 patients in group I and II respectively (p = 0.967). Fistula closure was done at least 3 months postoperatively, and there was no significant difference in success between the two groups. Two cases of glanular dehiscence were detected (one in each group); the patient from group I had a successful onlay island flap repair. CONCLUSIONS: Preputial preservation during Mathieu repair is a time-saving procedure with similar complication rate to traditional repair. Valuable local tissue is preserved to deal with complications that may occur.

Experience with impacted upper ureteral stones; should we abandon using semirigid ureteroscopes and pneumatic lithoclast?

INTRODUCTION: The AUA/EAU Ureteral Stones Guideline Panel reported that the stone free rate for the proximal ureteral stones is around 81% when treated by either SWL or ureteroscopy (URS).Complication rates, most notably ureteral perforation and long-term complications of URS such as stricture formation rates, have been reduced to < 5%. Moreover, impacted ureteral calculi are more difficult to fragment with SWL because of the lack of natural expansion space for stones, this result in a situation that is better managed by ureteroscopy. The aim of this study is to assess the efficacy, safety, and complications of impacted upper ureteral stone disintegration using semirigid ureteroscopes and pneumatic lithotripsy. METHODS: We retrospectively analyzed the records of 267 consecutive patients with impacted upper ureteral stones (9-20 mm) who were treated by semirigid ureteroscopes and pneumatic disintegration. The efficacy of treatment was estimated using the stone-free rate and all treatment related complications were analyzed. RESULTS: Except for 24 cases where the stone migrated to the kidney, the stone was successfully treated ureteroscopically, with a low rate of minimal complications such as mild hematuria (18.4%), short term low grade fever (13.5%). Only 3 patients (1.1%) had high grade fever and none had post operative stricture. CONCLUSION: The use of semirigid URS and pneumatic lithotripsy in impacted upper ureteral stones in experienced hands has very satisfactory results with minimal complications. When Holmium laser and flexible URS are not available, semirigid URS and pneumatic lithotripsy is a good alternative that shouldn't, yet, be abandoned.

The effectiveness of retinoic acid treatment in bladder cancer: impact on recurrence, survival and TGFalpha and VEGF as end-point biomarkers.

INTRODUCTION AND AIMS: Being best-studied superficial bladder cancer (SBC) chemopreventives, retinoids' negative studies and toxicity were stumbling. With proper understanding of retinoid metabolism, we aimed at investigating combined ketoconazole (a strong inhibitor of retinoic acid-catabolizing cytochrome P450s) all-trans retinoic acid (Keto-atRA) SBC treatment. VEGF and TGFalpha levels are end-point pathogenetic biomarkers involved in early SBC. RESULTS: Keto-atRA treatment significantly improved survival time and decreased recurrence rate compared to control disease group, with tolerable and reversible side-effects. Treatment normalized induced levels of VEGF and TGFalpha with a positive correlation between these cytokines. MATERIAL AND METHODS: Seven days after TURT visible tumor(s), combined atRA 1 mg/kg for five days a week + Keto 200 mg twice daily for five days a week for three months were given to 16 patients with SBC stages Ta and T1 with various grades. Three months follow up/20 months used white light cystoscopy and urinary cytology. Recurrence rate and survival time were compared to a retrospective group of 25 patients of comparable age, stage and grade with TURT as sole treatment for SBC. VEGF and TGFalpha were measured in urine and serum of 12 normal subjects and treated patients. Samples were collected just before TURT, one week after TURT, at the end of one month and at the end of three months of treatment. CONCLUSIONS: The combination and schedule used for Keto-atRA therapy effectively reduced recurrence rate and increased survival time of SBC patients probably through reduction of VEGF and TGFalpha as major mitogenic/angiogenic factors; possibly by eliminating malignant cells that produce them.

Bcl-XL and Bcl-2 expression in bilharzial squamous cell carcinoma of the urinary bladder: which protein is prognostic?

OBJECTIVES: Bcl-2 and Bcl-XL are the most important antiapoptotic members of the Bcl-2 family frequently overexpressed in bladder cancer. Overexpression of Bcl-XL bilharzial-related bladder cancer was associated with tumor progression. However, the negative prognostic value of Bcl-2 expression is still questionable. This work studied the expression of Bcl-XL and Bcl-2 immunohistochemically in bilharzial-related squamous cell carcinoma of the urinary bladder and determined their prognostic value in relation to recurrence after radical cystectomy. METHODS: A total of 72 patients with muscle-invasive bilharzial squamous cell carcinoma of the urinary bladder underwent radical cystectomy at our institution. The specimens were examined immunohistochemically for Bcl-XL and Bcl-2 expression. The patients were followed up for 3 years or until recurrence. The expression of Bcl-XL and Bcl-2 were related to the other prognostic indicators and patient survival. RESULTS: The expressions of both Bcl-2 and Bcl-XL were significantly different according to the grade of malignancy. Bcl-XL expression was significantly related to tumor recurrence, but Bcl-2 expression was not. CONCLUSIONS: To our knowledge, the present study is the first report of a negative prognostic value for Bcl-XL in bilharzial squamous cell carcinoma of the urinary bladder. However, this is another negative report on the prognostic value of bcl-2 in bilharzial bladder tumors.