Mahmoud El-Baz

Radical cystectomy for carcinoma of the bladder: 2,720 consecutive cases 5 years later.

PURPOSE We performed a critical analysis of the results of radical cystectomy for invasive bladder carcinoma treated at 1 center. MATERIALS AND METHODS Between 1970 and 2000, 2,090 men and 630 women with invasive bladder cancer were treated with 1-stage radical cystectomy and urinary diversion. Followup ranged from 0 to 34.2 years with a mean of 5.5 +/- 5.7. Survival data were correlated to patient and tumor characteristics using univariate and multivariate analysis. RESULTS Postoperative mortality was 2.6%. Squamous tumors accounted for 49.4% of cases, transitional cell carcinoma for 36.4% and adenocarcinoma for 9.6%. Regional lymph nodes were involved in 20.4% of cases. The 5 and 10-year disease-free survival rates were 55.5% and 50.03%, respectively. Evidence was provided that tumor stage, histological grade and lymph node status are the only independent variables which affect survival probability. CONCLUSIONS Contemporary cystectomy can be performed with minimal mortality. Radical cystectomy for organ confined disease is followed by good therapeutic results and enhances the possibilities for functional restoration. With stage progression there is a stepwise reduction in survival probability. The radical operation can provide disease-free survival for an important subgroup of node positive cases (27.3%). Additional therapy is needed to improve the oncological outcome for advanced locoregional disease.

Does the Extent of Lymphadenectomy in Radical Cystectomy for Bladder Cancer Influence Disease-Free Survival? A Prospective Single-Center Study

BACKGROUND Controversy exists regarding the optimal extent of lymphadenectomy and the number of lymph nodes to be retrieved at radical cystectomy (RC). OBJECTIVE To compare the disease-free survival of patients with standard lymphadenectomy (endopelvic region composed of the internal, external iliac, and obturator groups of lymph nodes) versus extended lymphadenectomy (up to the level of origin of the inferior mesenteric artery) at RC in a prospective cohort of patients at a single, high-volume center. DESIGN, SETTING, AND PARTICIPANTS Prospective data were collected from 400 consecutive patients treated with RC for bladder cancer by two high-volume surgeons at Mansoura Urology and Nephrology Center. Of the 400 patients, 200 (50%) received extended lymphadenectomy and the other 200 (50%) underwent standard lymphadenectomy at RC. The patients did not receive any neoadjuvant or adjuvant therapy. MEASUREMENTS Patient characteristics and outcomes are evaluated. RESULTS AND LIMITATIONS Median patient age for the entire group was 53.0 yr. Ninety-six patients (24.0%) had lymph node metastases. Median follow-up was 50.2 mo. Estimates of 5-yr disease-free survival in the extended lymphadenectomy group were 66.6% compared with 54.7% for patients with standard lymphadenectomy (p = 0.043). Extended lymphadenectomy was associated with better disease-free survival after adjusting for the effects of standard pathologic features (p = 0.02). When restricting the analyses to lymph node-positive patients, patients with extended lymphadenectomy had much better 5-yr disease-free survival compared with patients with standard lymphadenectomy (48.0% vs 28.2%; p = 0.029). The study was nonrandomized. CONCLUSIONS Extended lymphadenectomy is associated with better disease-free survival for bladder cancer patients with endopelvic lymph node involvement and should be considered in these patients.

Late malignancy in bowel segments exposed to urine without fecal stream

OBJECTIVES This study was constructed so as to screen malignant transformation after uroenteric reconstructions using bowel segments exposed to urine without fecal stream for more than 10 years. METHODS Follow-up data were available for 186 patients who underwent various uroenteric reconstructions using bowel segments exposed to urine without fecal stream for more than 10 years. There were 68 eligible patients with isolated rectosigmoid bladder, 23 with bladder augmentations (15 ileocystoplasty and 8 colocystoplasty), 57 with ileal ureter, and 38 with ileal loop conduit. Besides routine laboratory and radiologic investigations, urine for cytology was obtained from all patients. Moreover, endoscopy and random biopsy of the part of bowel exposed to urine were carried out in all patients. RESULTS Uroenteric malignancy was diagnosed in 4 patients (2%): 2 adenocarcinoma in an isolated rectosigmoid bladder, 1 transitional cell carcinoma following augmentation colocystoplasty, and 1 squamous cell carcinoma after ileal ureter. None of the patients developed tumors in ileal loop conduits. CONCLUSIONS Malignant changes do not only occur after ureterosigmoidostomy but are also observed after different uroenteric reconstructions not exposed to fecal stream. Hematuria, ureteral obstruction, and abnormal urine cytology are warning signs of malignancy. Routine cytology is recommended at least yearly beginning 10 years after surgery.

Interferon Therapy in Hemodialysis Patients with Chronic Hepatitis C: Study of Tolerance, Efficacy and Post-Transplantation Course

Background: The potential benefit of pre-transplant treatment of chronic hepatitis C on long-term evolution after renal transplantation is not clear. Methods: Fifty successive renal transplant candidates had their sera positive for HCV RNA and a biopsy-proven chronic hepatitis. Out of these, 18 patients received a standard course of interferon-α2b (IFN; 3 MU three times weekly after hemodialysis sessions for 6 months). Results: IFN was discontinued in 2 patients (11%) due to persistent leukopenia. HCV RNA turned negative in 10 patients of the treatment group and in none of the control group. Two patients of the IFN group had a virological relapse post-transplantation. Post-transplant follow-up periods were 41.5 ± 15 and 50 ± 16 months for the treated and control groups respectively. Transaminases remained normal in all patients of the IFN group after transplantation. In contrast, biochemical evidence of acute and chronic hepatitis was observed in 5 (p = 0.03) and 13 (p = 0.002) patients, respectively, of the control group. Logistic regression analysis identified non-receiving IFN before transplantation as a risk factor for post-transplant hepatic dysfunction (odds ratio = 11.7, p = 0.003) and for chronic allograft nephropathy (odds ratio = 11.6, p = 0.02). Conclusions: IFN-treated patients had a significantly better post-transplant hepatic function and significantly lower rates of chronic allograft nephropathy.

Comparison of Sirolimus with Low‐Dose Tacrolimus Versus Sirolimus‐based Calcineurin Inhibitor‐Free Regimen in Live Donor Renal Transplantation

Between May 2001 and January 2003, 132 live donor renal allotransplant recipients were included in a prospective, randomized controlled trial where they were divided into two groups. All patients received steroids and basiliximab induction therapy. For maintenance immunosuppression, tacrolimus and sirolimus were used in group A. In group B, mycophenolate mofetil (MMF) and sirolimus were utilized. Patients were followed up for a minimum of 24 months. One‐year patient and graft survival rates were not significantly different between group A (96.9%, 92.3%) and group B (100%, 98.4%), respectively. However, the incidence of biopsy‐proven acute rejection was less in group B but the difference was not statistically significant (13.5% vs. 18.5% in group A). Statistically significant better renal function was encountered among group B patients at two years post‐transplantation as measured by serum creatinine (1.25 vs. 1.43 mg/dl; P = 0.017) and calculated glomerular filtration rate (GFR) (94.9 vs. 79.6 ml/min; P = 0.005). One year protocol biopsies showed insignificant differences relative to chronic allograft damage index (CADI) between either group (Group A: 2.41 vs. Group B: 2.69; P = 0.436). Conclusion: Similar outcome was noted among patients in whom calcineurin inhibitors were not included in their immunosuppressive regimen. The long term impact of this observation on graft survival and function needs longer follow up.

Predictors of prostate cancer on extended biopsy in patients with high-grade prostatic intraepithelial neoplasia: a multivariate analysis model.

To define the importance of extended biopsy in patients with high‐grade prostatic intraepithelial neoplasia (HGPIN) and to define predictors of cancer in extended biopsy in patients with HGPIN, using multivariate analysis.

Intravesical epirubicin versus doxorubicin for superficial bladder tumors (stages pTa and pT1): a randomized prospective study.

PURPOSE We performed a prospective, randomized, controlled study to compare intravesical epirubicin and doxorubicin as adjuvant therapy after endoscopic resection of superficial bladder tumor. MATERIALS AND METHODS We randomly allocated 253 eligible patients to 4 study arms. Seven to 14 days after transurethral bladder tumor resection instillation of the intravesical agent was instituted, including 50 and 80 mg. epirubicin in study arms 1 and 2, respectively, and 50 mg. doxorubicin in arm 3. Control arm 4 included patients who underwent transurethral bladder tumor resection alone. Instillation was repeated weekly for 8 weeks and monthly thereafter to complete 1 year of treatment. All patients were followed every 3 months by cystourethroscopy, urine cytology and deoxyribonucleic acid flow cytometry for 12 to 48 months (mean 30.1). RESULTS Rates of recurrence were significantly lower in the chemotherapy groups than in controls (p < 0.001) and in the epirubicin groups than in the doxorubicin group (p = 0.02). In arms 1 to 4 recurrence rates were 25, 17.6, 36.7 and 65.6%, respectively. Recurrence rates per 100 patient months were 0.83, 0.60, 1.18 and 2.73, respectively, which were significant statistically, and lower after chemotherapy in general and epirubicin in particular (p < 0.05). Mean interval to first recurrence was 16, 15.4, 18.9 and 6.3 months, respectively, with a significant difference between the chemotherapy and control groups (p < 0.05). Progression to muscle invasive disease occurred in 7 (10.9%), 3 (4.4%), 6 (10%) and 5 patients (8.2%), respectively, in arms 1 to 4 (p > 0.05). We studied the relationships among different risk factors, and patterns of recurrence and progression. For pT1 tumors recurrence rates in arms 1 to 4 were 26.3, 17.8, 39.3 and 70.9%, respectively, which were significantly lower in the chemotherapy group than in controls (p < 0.001) and in the epirubicin groups than in the doxorubicin group (p = 0.01). Toxic and untoward side effects developed in 10 (15.6%), 16 (23.5%) and 25 (41.7%) patients in chemotherapy arms 1 to 3, respectively, with a marginal insignificant difference between low and high dose epirubicin (p = 0.3), and significantly lower toxicity rates in arms 1 and 2 than in 3 (p = 0.002). A contracted bladder developed in 2.1% of all patients who received chemotherapy. CONCLUSIONS This study demonstrates that epirubicin has better efficacy and lower toxicity than doxorubicin when used as an intravesical agent.

Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2.

PURPOSE We investigated the association of the apoptosis related proteins Bcl-2, Bcl-x, Bax and Bak, p53, the adhesion molecule E-cadherin, the receptor proteins epidermal growth factor receptor and c-erbB-2, and the proliferation markers proliferating cell nuclear antigen and Ki-67 with the clinical outcome of bilharzial related transitional cell carcinoma and squamous cell carcinoma. MATERIALS AND METHODS Cystectomy specimens from 109 patients with organ confined, muscle invasive stage, pT2pN0M0, bilharziall positive bladder cancer were examined, including 60 with squamous cell carcinoma and 49 with transitional cell carcinoma. Immunohistochemical results were correlated with tumor progression. RESULTS In squamous cell carcinoma but not in transitional cell carcinoma the loss of epidermal growth factor receptor, Bax and Bak was significantly associated with higher histological grade (p = 0.02, 0.006 and 0.01, respectively). On univariate analysis patients with transitional cell carcinoma had a poorer prognosis than those with squamous cell carcinoma. p53 Over expression and the loss of Bak positivity were associated with shortened progression-free survival in transitional cell carcinoma (p = 0.006 and 0.04, respectively), and squamous cell carcinoma (p = 0.00001 and 0.04, respectively). In squamous cell carcinoma high tumor grade (p = 0.02) and in transitional cell carcinoma high labeling indexes for MIB-1, Bcl-x expression and c-erbB-2 positivity (p = 0.03, 0.02 and 0.04, respectively) were associated with a poorer prognosis. On multivariate analysis p53 emerged as a significant prognostic factor for each condition. Additional independent prognostic factors were proliferating cell nuclear antigen for squamous cell carcinoma, and MIB-1, Bcl-x and Bax for transitional cell carcinoma. CONCLUSIONS Bilharzial related transitional cell carcinoma and squamous cell carcinoma of the bladder differ in interims of protein expression and prognosis. Independent prognostic factors were p53, MIB-1, Bcl-x, and Bax in the former disease, and p53 and proliferating cell nuclear antigen in the latter disease.

Impact of Treatment of Dyslipidemia on Renal Function, Fat Deposits and Scarring in Patients with Persistent Nephrotic Syndrome

In this study 43 patients with idiopathic nephrotic syndrome were randomly distributed into 2 age- and sex-matched groups. The first group was given fluvastatin while the second was used as control. The cases in the 2 groups were evaluated clinically, biochemically (creatinine clearance, albumin, 24-hour proteinuria, and lipogram), neurologically, and histopathologically (examination of renal biopsies obtained basally and after 1 year of treatment with fluvastatin). In the fluvastatin-treated group but not in the control group, we observed a significant reduction in cholesterol, low-density lipoprotein, and triglyceride. Clinical and laboratory assessment showed satisfactory tolerance of the drug by the patients. Proteinuria, serum albumin and creatinine clearance values were significantly better in the statin-treated patients. There was no difference in glomerular sclerosis between the 2 groups while interstitial fibrosis and renal fat deposits were less in the statin-treated group. The reduction in renal fat deposits in the statin-treated group was highly significant, while that of interstitial fibrosis was not. We conclude that: (1) statin can be safely and effectively used in the treatment of dyslipidemia in patients with persistent idiopathic nephrotic syndrome; (2) control of dyslipidemia in nephrotic patients is associated with better control of proteinuria and creatinine clearance; (3) statin treatment may cause regression of renal fat deposits in patients with nephrotic syndrome, and (4) longer term studies are still required to study further possible beneficial effects on renal histology and disease progression.

NUMERICAL ABERRATIONS OF CHROMOSOMES 7, 9 AND 17 IN SQUAMOUS CELL AND TRANSITIONAL CELL CANCER OF THE BLADDER: A COMPARATIVE STUDY PERFORMED BY FLUORESCENCE IN SITU HYBRIDIZATION

PURPOSE Since squamous cell differs from transitional cell cancer regarding histopathology, clinical outcome and etiology, the underlying genetic effects of these 2 tumor types may also be different. We compared numerical aberrations of chromosomes 7, 9 and 17 in bilharzial squamous cell carcinoma, and bilharzial and nonbilharzial transitional cell carcinoma by fluorescence in situ hybridization, and correlated the findings to p53 positivity of the 3 tumor types. MATERIALS AND METHODS Cystectomy for invasive bladder cancer was performed in 169 men and 51 women with a mean age of 54.8 years (range 28 to 83). Of the 220 patients 100 (45.4%) had histologically verified bilharzial squamous cell carcinoma, 61 (27.7%) bilharzial transitional cell carcinoma and 59 (26.8%) nonbilharzial transitional cell carcinoma. Using fluorescence in situ hybridization cystectomy specimens were evaluated for numerical aberrations of chromosomes 7, 9 and 17, and p53 detection was performed by immunohistochemistry. RESULTS Aberrations of chromosome 7 were observed in 79% of the bilharzial squamous cell carcinoma specimens, and 100% and 93.2% of bilharzial and nonbilharzial transitional cell carcinoma specimens, respectively (p = 0.00011). Aberrations of chromosome 9 were seen in 92% of squamous cell carcinoma specimens but in only 52.4% and 60.9% of bilharzial and nonbilharzial transitional cell carcinoma, respectively (p < 0.00001). Aberrations of chromosome 17 were found in only 29% of squamous cell carcinoma specimens, compared to 83.6% and 84.7% aberrations of chromosome 17 in both transitional cell carcinoma groups, respectively (p < 0.00001). The p53 over expression was similar in all 3 tumor types with 82% for squamous cell carcinoma, and 73.7% for bilharzial and 81.3% for nonbilharzial transitional cell carcinoma (not significant, p = 0.5285). CONCLUSIONS Our data show clear differences between chromosomal patterns of invasive bilharzial squamous cell carcinoma and invasive bilharzial or nonbilharzial transitional cell carcinoma but similar frequencies of p53 over expression in all 3 tumor types. However, aberrations of chromosome 9 were observed in all analyzed groups, which confirms the 2 pathways in the oncogenesis of squamous cell and transitional cell carcinoma at the cytogenetic level as suggested by molecular studies.