Emre Tüzel

Transitional cell carcinoma of the ureter and renal pelvis

Transitional cell carcinoma (TCC) of ureter and renal pelvis is relatively uncommon. Smoking, occupational carcinogens, analgesic abuse, Balkan nephropathy are the risk factors. Cytogenetic studies revealed that the most frequent aberration is the partial or complete loss of chromosome 9. Approximately 20-50% of patients with upper urinary tract (UUT) TCC have bladder cancer at some point on their course, whereas the incidence of UUT TCC after primary bladder cancer is 0.7-4%. Excretory urography and retrograde pyelography are the conventional diagnostic tools; however, ureteropyeloscopy combined with cytology and biopsy is more accurate. Grade and stage of the disease have the most significant impact on survival. Nephroureterectomy with bladder cuff excision has been the mainstay of treatment. Local resection may be appropriate for distal ureteral lesions especially when the disease is low grade and stage. Advances in endourology have made it possible to treat many tumors conservatively. Ureteroscopic and to a certain extent percutaneous surgical approaches are widely used today especially in patients with low grade, low stage disease. Endoscopic close surveillance is mandatory for these patients. Adjuvant topical therapies appear to be safe but confirmation of any benefits awaits the results of further large studies. More recently, laparoscopic techniques have become a viable alternative to open surgery, but long term cancer control data are lacking. Aggressive surgical resection does not affect the outcome of patients with advanced disease. Adjuvant radiotherapy is ineffective, and systemic chemotherapy results in a low complete response rate for patients with metastases.

Recent advances in kidney cancer and metastatic disease.

RCC accounts for < 3% of adult solid tumours, and each year 30 000 new cases in the USA and 20 000 in the European Union are detected. Men are affected twice as often as women, with the highest incidence in those aged 50±70 years. Despite modern imaging methods and early diagnosis, a third of patients present with metastatic disease and up to half with localized disease progression after radical nephrectomy. The incidence of RCC has increased by >30% in the last decade, as a result of better imaging, early diagnosis and environmental factors. Except for hereditary forms, several risk factors have been identi®ed, e.g. smoking, obesity, hyper tension, occupational petrol and heavy-metal exposure, diuretics, haemodialysis, and pre-existing kidney diseases, including stones and infections [1].

METALLOTHIONEIN EXPRESSION IN RENAL CELL CARCINOMA: SUBCELLULAR LOCALIZATION AND PROGNOSTIC SIGNIFICANCE

PURPOSE We investigated the immunohistochemical localization of metallothionein (MT) in renal cell carcinoma and determined the potential role of MT expression as a possible prognostic variable for tumor proliferation and progression. MATERIALS AND METHODS Tumor tissue blocks from 70 patients with renal cell carcinoma who underwent radical or partial nephrectomy were investigated. Mean followup plus or minus standard error was 36 +/- 3 months. Immunohistochemical testing was performed by the avidin-streptavidin method using a monoclonal mouse antiMT antibody. MT staining intensity in samples was evaluated semiquantitatively. The subcellular distribution of MT was also determined. Staining characteristics were compared with the clinicopathological results. RESULTS MT immunostaining was found in 39 of 70 tumors (55.7%) and subcellulary MT was localized in the cytoplasm, nucleus and cell membrane. The survival of patients with MT immunostaining was significantly worse than that of those with MT negative results (p = 0.02). A significant relationship of higher tumor grade and MT staining intensity was observed in grades I and III (p = 0.01), and grades II and III (p = 0.02) tumors. No association was found of MT expression and pathological stage. Sarcomatoid tumors showed significantly higher MT expression than clear cell, papillary, granular or chromophobe tumors (p = 0.02, 0.001, 0.01 and 0.01, respectively). MT expression was not an independent prognostic variable. CONCLUSIONS MT over expression seems to be associated with malignant behavior and poor prognosis in renal cell carcinoma. Therefore, MT expression may be considered a useful marker of less differentiated and more aggressive renal cell carcinoma.

Primary renal lymphoma of mucosa-associated lymphoid tissue

Mucosa-associated lymphoid tissue-type lymphomas have recently been recognized as a distinctive form of B-cell malignant lymphoma. In contrast to other types of low-grade lymphomas, these tumors have a tendency to be localized at diagnosis and to be curable with local therapy. We report an unusual case of primary localized low-grade lymphoma of mucosa-associated lymphoid tissue arising in the kidney. The patient underwent radical nephrectomy and was free of disease at 28 months of follow-up without additional treatment. Once properly staged and classified, lymphoma of mucosa-associated lymphoid tissue involving the kidney can be managed by radical nephrectomy and follow-up.

Expression of p53 and mdm2 and Their Significance in Recurrence of Superficial Bladder Cancer

The purpose of this study is to evaluate the expression of p53 and mdm2 and to determine whether they may be used as additional predictors of recurrence in superficial transitional cell carcinoma of the bladder. Paraffin sections of 80 patients with superficial transitional cell carcinoma of the bladder, who were treated with transurethral resection, were stained with p53 and mdm2 antibodies using the standard avidin biotin immunoperoxidase method. Nuclear staining for both p53 and mdm2 was calculated as the percentage of labeled nuclei out of a total number of tumor cells counted. The percentage of p53- and mdm2-positive cells showed a significant relationship with tumor grade and recurrence (p = 0.002 and p = 0.016; p = 0.01 and p = 0.003, respectively). In addition, a weak inverse relationship was found between p53 and mdm2 values (r = -0.184). p53 and mdm2 reactivities are valuable parameters in predicting recurrence in superficial bladder cancer. Thus, mdm2 expression appears to play a role in predicting biologic behavior in superficial transitional carcinoma of the bladder.

Significance of Tissue Laminin P1 Elastase and Fibronectin Levels in Transitional Cell Carcinoma of the Bladder

Objective: Elastase is a serine protease which hydrolyses connective tissue components. Laminin and fibronectin also play an important role in progression and invasion of cancer. The purpose of this study is to investigate the relation between tissue elastase, laminin P1 and fibronectin levels and tumor characteristics, and analyze the potential of these as prognostic factors in transitional cell carcinoma (TCC) of the bladder. Methods: Thirty–four patients with TCC of the bladder and 11 controls were included in this study. Elastase and fibronectin levels in tissue homogenates were determined using an enzyme immunoassay and laminin P1 by radioimmunoassay. Mean follow–up was 43 months. Results: The mean elastase level in bladder carcinoma tissue was 120±11.42 ng/homogenate protein, while normal tissue level was 12.36±2.70 (p<0.01). The carcinoma and normal tissue mean laminin P1 levels were 7.02±0.37 U and 0.65±0.10 U/mg homogenate protein, respectively (p<0.01). The mean fibronectin level was 19.97±1.45 ng/mg homogenate protein in the carcinoma tissue and 2.16±0.40 in normal tissue (p<0.01). There was no correlation between tumor stage, grade, size, multiplicity and elastase, laminin P1 and fibronectin levels. Conclusion: These results provide evidence that tissue elastase, laminin P1 and fibronectin levels increase in TCC of the human bladder. Further studies including serum and urine levels should be performed in order to analyze their value as tumor markers in a larger group of patients.

Giant angiomyolipoma associated with marked pulmonary lesions suggesting lymphangioleiomyomatosis in a patient with tuberous sclerosis

The association between Tuberous Sclerosis (TS) and Angiomyolipoma (AML) is well known. A patient with TS and giant AML mimicking Renal Cell Carcinoma (RCC), measuring 29 × 18 × 11 cm, weighing 4700 gr is presented. Imaging studies revealed coexistent pulmonary lymphangioleiomyomatosis and concurrent renal and pulmonary involvement is extremely rare in patients in TS. We believe that the growth potential of this hamartomatous lesion may reach to a life threatening size.

Is Magnetic Resonance Imaging Necessary in the Staging of Prostate Cancer

Objective: To evaluate the necessity of using magnetic resonance imaging (MRI) in the staging of patients with clinically localized prostate cancer. Methods: Sixty-one patients with prostate cancer were evaluated with MRI for preoperative staging with a conventional body-coil (Siemens Magnetom, 1.0 Tesla superconducting system). Twenty-nine patients underwent radical prostatectomy for presumed clinically localized disease. Of those, 17 were staged both with MRI and computerized tomography (CT). The remaining patients were staged with CT alone. MRI and CT findings, and the final pathologic staging of patients are reviewed. Results: On pathological examination of the surgical specimens, the tumor was found to extend beyond the prostate in 7 patients (41%). Among the 17 patients who were operated, extraprostatic extension (EPE) was detected accurately in 3 patients with MRI (sensitivity 20%, specificity 92%, accuracy 70.5%). No metastatic lymph nodes were detected on the basis of MRI (sensitivity 0%, specificity 93%, accuracy 88.2%). In 1 patient EPE was correctly identified by CT (sensitivity 14%, specificity 100%, accuracy 64.7%). Conclusion: Neither MRI with conventional body-coild nor CT are sufficient to indicate local extension of disease in clinically localized prostate cancer.

Prognostic significance of nuclear morphometry in renal cell carcinoma

Objective  To assess nuclear morphometry as a predictor of prognosis in patients with renal cell carcinoma (RCC).

Effects of finasteride on the vascular surface density, number of microvessels and vascular endothelial growth factor expression of the rat prostate

AbstractIntroduction: Finasteride is a 5-alpha-reductase inhibitor used in the medical treatment of benign prostatic hyperplasia (BPH) and appears to be effective in treating prostatic bleeding secondary to BPH. The exact mechanism of this effect is not known. The aim of this study was to evaluate the effects of finasteride on the vascular surface density (VSD), number of microvessels (NVES) and vascular endothelial growth factor (VEGF) expression of the rat prostate. Materials and methods: Nineteen adult male rats were used. Finasteride was given to 14, and there were 5 in the control group. Finasteride 80 mg/kg was administered daily via orogastric tube as a suspension for three months. Rats were sacrificed and vascular structures of the prostates were labelled immunohistochemically using CD31 antibodies. VSD and NVES of the prostates were assessed by means of a peroxidase labeled streptavidin-biotin method. VEGF expression was examined by immunohistochemistry using VEGF monoclonal antibody. Results: Mean prostatic weights were decreased significantly in rats given finasteride (p=0.0001). Although an increase in VSD was detected in the finasteride group it was not significant (p=0.26). NVES was significantly increased in the finasteride group (p=0.033). No significant difference was detected between the two groups in terms of VEGF expression (p=0.48). Conclusion: Finasteride does not seem to decrease VSD, NVES and VEGF expression at the level of the rat prostate. The effect of reduction of bleeding in BPH is likely to be due to its effect on shrinking glandular hyperplasia which might enhance vessel wall stability rather than decreasing overall vascularity.