Clinical versus Pathologic staging of Renal Tumors: Role of Multi-Detector CT Urography.

INTRODUCTION: Our ability to diagnose renal cell carcinoma (RCC) has increased in the past 30 years as a result of the extensive application of imaging techniques, such as ultrasonography, computed tomography, and magnetic resonance imaging. Multi-detector computed tomography (MDCT) remains the most appropriate imaging modality for the diagnosis and staging of RCC. The aim of this work was to compare the findings of MDCT with surgical pathology to determine the accuracy of delineating tumor size, localization, organ confinement, lymph node metastases, and the extent of tumor thrombus in the renal vein and inferior vena cava. METHODS: The clinical, surgical, and anatomo-pathologic records of 99 patients treated by nephrectomy (radical or partial) for solid renal tumors at Theodor Bilharz Research Institute and Nasser Institute from 2005 to 2011 were reviewed retrospectively. All cases were staged pre-operatively with abdominal MDCT (pre- and post-contrast enhancement) in addition to the routine biochemical, hematological, and radiological work-up. The tumors' histologic types were determined according to the WHO classification of renal tumors in adults in 2004, and staging was updated to the TNM 2010 system. Data were analyzed using the t-test. RESULTS: The mean age was 52 (range 21-73). Seventy-eight patients were males, and 21 patients were females (Male/Female ratio: 3.7:1). There were no significant differences in the mean tumor size between radiographic and pathologic assessments in different tumor stages. The overall incidence of lymph node invasion in surgical specimens was 76%, whereas MDCT showed a positive incidence in 68.4% of cases (false negative result in 7 cases, 7.6%). CONCLUSION: Our findings indicated that MDCT urography is an accurate method to estimate renal tumor size, lymph node, vascular and visceral metastases preoperatively. Also, preoperative staging of renal tumors with MDCT represents a valuable and accurate tool.

Mistletoe Plant Extract in Patients with Nonmuscle Invasive Bladder Cancer: Results of a Phase Ib/IIa Single Group Dose Escalation Study.

PURPOSE: We determined the maximum tolerated dose, safety and effectiveness of intravesical instillation of mistletoe extract after transurethral resection of nonmuscle invasive bladder cancer. MATERIALS AND METHODS: In this single group dose escalation study patients with nonmuscle invasive bladder cancer were treated with weekly instillations of mistletoe extract for 6 weeks. Four weeks before instillation therapy all patients underwent transurethral resection of bladder tumors. During this procedure a marker tumor was left. At 12 weeks after the start of instillation therapy transurethral resection of the marker tumor or biopsy of the former marker tumor location was done so that patients were tumor free when entering followup until week 48. During the followup clinical assessment laboratory tests for safety and cystoscopy were done every 12 weeks. RESULTS: A total of 36 patients were treated with increasing doses of mistletoe extract. We found no dose limiting toxicity up to a dose of 675 mg of plant extract. Besides local reactions we saw hints that pyrexia may develop. All adverse events were well manageable. At 12 weeks a marker tumor remission rate of 55.6% (95% CI 38.1 to 72.1) was achieved. At 1 year a recurrence rate of 26.3% (95% CI 9.1 to 51.2) was observed. CONCLUSIONS: In this study intravesical instillation of mistletoe extract as treatment in patients with nonmuscle invasive bladder cancer was shown to be safe and well tolerated. Promising data on efficacy were observed and will be further investigated in a phase III study.

Single-step renal dilatation in percutaneous nephrolithotomy: A prospective randomised study.

OBJECTIVE: To perform an economical single-step renal dilatation (RD) during percutaneous nephrolithotomy (PCNL), using directly a 30-F Amplatz dilator over the central Alken dilator, in a trial to reduce the operative duration and radiation exposure during RD while avoiding an exchange of dilators that might increase the risk of blood loss. PATIENTS AND METHODS: In a prospective randomised study including 49 patients divided into two groups, the first had RD before PCNL using the standard metallic telescopic dilators (Alken), and the second had RD using the 30-F Amplatz dilator over the central Alken dilator. The operative duration, with X-ray exposure, was calculated. The procedure outcome in terms of complications, stone-free rates and hospital stay was evaluated statistically. RESULTS: The tract was dilated correctly in all cases. The operative duration and X-ray exposure was shorter in patients undergoing single-step RD (P < 0.05). There were perioperative complications, according to the Clavien grading system, in 17 (34%) patients but there was no statistically significant difference between the groups. The stone-free rates were comparable in both groups. CONCLUSION: A single-step RD during PCNL is feasible, with a shorter operative duration and X-ray exposure. The outcomes were comparable with those of a standard metallic telescopic RD.

Percutaneous nephrolithotomy in the supine position: Safety and outcomes in a single-centre experience.

OBJECTIVES: To assess the feasibility of performing percutaneous nephrolithotomy (PCNL) with the patient supine. Although PCNL with the patient prone is the standard technique for treating large (>2 cm) renal stones including staghorn stones, we evaluated the safety and efficacy of supine PCNL for managing large renal stones, with special attention to evaluating the complications. PATIENTS AND METHOD: In a prospective study between January 2010 and December 2011, 54 patients with large and staghorn renal stones underwent cystoscopy with a ureteric catheter inserted, followed by puncture of the collecting system while they were supine. Tract dilatation to 30 F was followed by nephroscopy, stone disintegration using pneumatic lithotripsy, and retrieval using a stone forceps. All patients had a nephrostomy tube placed at the end of the procedure. The results were compared with those from recent large series of supine PCNL. RESULTS: The median (range) operative duration was 130 (90-210) min, and the mean (SD) volume of irrigant was 22.2 (3.7) L. One puncture was used to enter the collecting system in 51 renal units (94%), while three units (6%) with a staghorn stone needed two punctures. The stone clearance rate was 91%, and five patients had an auxiliary procedure. There were complications in 15 patients (28%). All patients were stone-free at a 3-month follow-up. CONCLUSION: Supine PCNL is technically feasible; it has several advantages to patients, urologists and anaesthesiologists. It gives stone-free rates and a low incidence of organ injury comparable to those in standard prone PCNL.

Nuclear localization of COX-2 in relation to the expression of stemness markers in urinary bladder cancer.

Inflammation may activate stem cells via prostaglandin E2 (PGE2) production mediated by cyclooxygenase-2 (COX-2) expression. We performed an immunohistochemical analysis of the expression of stemness markers (Oct3/4 and CD44v6) and COX-2 in urinary bladder tissues obtained from cystitis and cancer patients with and without Schistosoma haematobium infections. Immunoreactivity to Oct3/4 was significantly higher in S. haematobium-associated cystitis and cancer tissues than in normal tissues. CD44v6 expression was significantly higher in bladder cancer without S. haematobium than in normal tissues. COX-2 was located in the cytoplasmic membrane, cytoplasm, and nucleus of the cancer cells. Interestingly, the nuclear localization of COX-2, which was reported to function as a transcription factor, was significantly associated with the upregulation of Oct3/4 and CD44v6 in bladder cancer tissues with and without S. haematobium infection, respectively. COX-2 activation may be involved in inflammation-mediated stem cell proliferation/differentiation in urinary bladder carcinogenesis.

Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosoma haematobium infection.

To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-κB in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-κB activation, leading to tumor development.

Molecular markers and bladder carcinoma: Schistosomal and non-schistosomal.

OBJECTIVES: Detection of telomeric repeat amplification protocol (TRAP) activity, the human telomerase reverse transcriptase (hTERT), tumor suppressor gene (p53) and proliferating marker (MIB-1) in bladder specimens. DESIGN AND METHODS: Specimens were obtained from 85 patients and 10 controls. TRAP technique and immunohistochemistry (IHC) method were performed. RESULTS: TRAP activity, hTERT, p53 and MIB1 were detected in 62.4%, 65.9%, 57.6% and 62.4% of all 85 patient cases, respectively. TRAP activity was detected in 75% of schistosomal urothelial carcinoma, 100% in schistosomal squamous cell carcinoma (SQCC) and 71.4% in non-schistosomal urothelial carcinoma. hTERT protein was detected in schistosomal urothelial carcinoma (83.3%), 93.3% in schistosomal SQCC and 75.7% in non-schistosomal urothelial carcinoma. CONCLUSIONS: TRAP and hTERT are useful for the detection of telomerase with special emphasis on their role in the detection of schistosomal-associated bladder cancer. Correlation of TRAP and hTERT protein with MIB1 and p53 reveals the importance of telomerase as a new marker in cancer bladder.

Possible role of telomerase and sFas in pathogenesis of various bladder lesions associated with schistosomiasis.

OBJECTIVES: To find the role of telomerase and sFas in the pathogenesis of various bladder lesions associated with schistosomiasis and to correlate the results with clinicopathological parameters. DESIGN AND METHODS: One hundred bladder samples were taken, including 65 cases with bladder cancer, 25 cases with chronic cystitis and 10 samples from normal bladder tissue as control. Telomerase activity was measured using TRAP and hTERT techniques. Also, sFas was detected by ELISA technique in serum of all patients. RESULTS: TRAP activity was detected in 78.5%; there was a significant increase in the number of positive cases in schistosomal urothelial carcinoma (TCC) and squamous cell carcinoma (SCC) compared to control and non-schistosomal urothelial carcinoma at (p<0.01 for each). TRAP activity was positive in 100% of high grade urothelial carcinoma compared to low grade and 92% positive in invasive tumors compared to non invasive tumors. hTERT protein was detected in 75.4% of bladder cancer cases; there was a significant increase in the number of positive cases in schistosomal urothelial carcinoma and SCC compared to control and non schistosomal urothelial carcinoma (p<0.01 for each). hTERT was positive in 100% of high grade and invasive TCC. sFas was detected in 64.6% in bladder cancer cases; there was a significant increase in the number of positive cases in SCC compared to control and non-schistosomal urothelial carcinoma. CONCLUSION: There is an increase in telomerase activity and over-expression of hTERT proteins in schistosomal associated bladder cancer (SABC) in comparison to non schistosomal associated bladder cancer (non SABC). Also, there is an increase in sFas level in SCC compared to other the groups. Both, telomerase activity by TRAP and hTERT and sFas may be of significance in the development of SABC. They may also be useful markers to identify bladder carcinoma through telomerase inhibition.

Effectiveness of a single immediate mitomycin C instillation in patients with low risk superficial bladder cancer: short and long-term follow-up.

PURPOSE: We analyzed the impact of a single Mitomycin C instillation in patients with low risk superficial bladder cancer with short and long-term follow-up. PATIENTS AND METHODS: This study was conducted on 63 patients with low risk superficial bladder transitional cell carcinoma (TCC), admitted to the Urology Department, Theodor Bilharz Research Institute (TBRI) during the period from January 2002 to August 2005. All patients had a 2 cm. or less single, papillary, primary or recurrent tumor and were disease-free for more than 1 year. Patients with muscular invasion, G III tumor or bladder carcinoma in situ on pathological examination were excluded from the study. The tumor was completely resected before patients were divided randomly into 2 arms: first group who have received no further treatment (control group) and a second group with a single immediate instillation of 30 mg. Mitomycin C (mitomycin C group). Recurrences were considered early if they occurred within the first 2 years of follow-up. RESULTS: At 24-months follow-up, the recurrence-free interval was significantly increased and recurrence, recurrence per year and tumor per year rates were decreased in the mitomycin C group compared to the control group. Early recurrence was (16.1%) in the mitomycin C group versus (34.3%) in the control group. It was noted also that early recurrences were concentrated in the first year in the control group (18.7%) versus (3.2%) in the mitomycin C group. However, at long-term follow-up, these differences were not statistically significant (26.9%) in the mitomycin C group versus (28.6%) in the control group, and the recurrence-free interval curves were parallel. A significant relationship between early and late recurrences was found in the mitomycin C, but not in the control group. Shorter hospital stay and catheterization periods were noted in the mitomycin C group compared to the control group, but the differences were not statistically significant. CONCLUSION: These data confirm the positive effect of a single immediate mitomycin C instillation in patients with low risk superficial bladder cancer. This benefit is limited to early recurrence and is not maintained with long-term follow-up. Thus, this approach is an alternative to observation or classic long-term intravesical chemotherapy. Our study also suggests that cell implantation as a mechanism of early recurrence can be controlled or minimized with a single mitomycin C instillation.