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Abstract: Patient''s history, physical examination, laboratory tests, and radiographic evaluation are the cornerstones of postoperative surveillance. It has been shown that localized renal cell carcinoma (RCC) can recur in nearly all organs of the body, but most commonly in the lung, bone, liver, brain, and renal fossa. Lung metastases can be sensitively detected through radiographic evaluation. Treatment of lung metastases might prolong survival, which supports surveillance x-ray or computed tomography scans. Surgical treatment of early detected liver metastases and local recurrences may also prolong survival, which supports a close abdominal surveillance program. Brain and bone metastases are usually symptomatic when they occur, and their treatment is generally palliative. Hence, surveillance protocols do not usually include their routine radiographic evaluation. Because partial nephrectomy does not increase the risk of local recurrence over radical nephrectomy, we recommend identical surveillance for completely resected tumors regardless of surgical approach. The risk of recurrence after nephrectomy is generally related to tumor stage, tumor grade, and patient performance status. The majority of recurrences occur within the first 5 years after surgery, supporting a more intense surveillance strategy within the first 5 years. The University of California Integrated Staging System (UISS) combines TNM stage, Fuhrman grade, and performance status, and categorizes patients into 3 different risk groups. The current surveillance protocol at our institution is based on the UISS. It is expected that molecular markers such as p53 will allow more individualized surveillance strategies in the future. [Copyright &y& Elsevier]

Abstract: Over the past 2 decades, a greater understanding of the basic biology and genetics of kidney cancer has occurred. Surgical techniques have also evolved, and technological advances have made possible new methods of managing renal tumors. The most extensively used system to provide prognostic information for renal cell carcinoma (RCC) is currently the tumor, nodes, metastasis (TNM) staging system. Emerging data over the last few years has questioned whether further revisions are needed and if improvements can be made with the introduction of new, more accurate and predictive prognostic factors. The recent discovery of molecular tumor biomarkers are expected to revolutionize the staging of RCC and potentially lead to the development of new therapies based on molecular targeting. This review will examine the current staging modalities and prognostic factors associated with RCC as well as the selection of patients most likely to benefit from clinical trials. [Copyright &y& Elsevier]

Abstract: Most cancers comprise a heterogenous population of cells with marked differences in their potential to proliferate as well as the ability to reconstitute the tumor upon transplantation. Cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. Dysregulation of stem cell self-renewal is a likely requirement for the development of cancer. Cell signaling pathways shared by stem cells and cancer cells lend further evidence for a possible link between these 2 populations of cells. Study of the differentiation pathways of normal and abnormal prostate growth has led to the development of a stem cell model for prostate cancer. The basal layer of the normal prostate is believed to be populated by prostate epithelial stem cells and a population of transit-amplifying cells intermediate in differentiation to the stem and fully differentiated cells. There is recent evidence suggesting that prostate cancer occurs from malignant transformation of stem/progenitor cells, thereby resisting apoptosis and spawning proliferation. This new model for prostate cancer will have significant ramifications for the way this disease is studied and treated. Furthermore, through targeting the prostate cancer stem cell and its dysregulated self-renewal, therapies for treatment of prostate cancer are likely to improve. [Copyright &y& Elsevier]

Abstract: Recent advances in the understanding of the pathogenesis, behavior, and molecular biology of renal cell carcinoma (RCC) have paved the way for developments that may enhance early diagnosis, better predict prognosis, and improve survival. Reliable predictive factors are essential for the stratification of patients into clinically meaningful categories that can be used to provide patients with counseling regarding prognosis, select treatment modalities, and determine eligibility for clinical trials. The TNM (tumor, nodes, metastasis) staging system is currently the most extensively used staging system for RCC, but it has undergone systematic revisions as a result of emerging data. Comprehensive integrated staging systems that combine important clinical and pathological variables have been created in an attempt to improve prognostication. Although staging has improved with the development of integrated systems, the incorporation of molecular tumor markers are expected to revolutionize the staging of RCC. This article reviews the important molecular markers in RCC to date and discusses their role in the diagnosis, prognostication, and therapy of patients with RCC. [Copyright &y& Elsevier]

Bacillus Calmette-Gue´rin (BCG) and interferon-α2B (IFN-α2B) have both been individually used for the intravesical treatment of superficial bladder cancer. We report our experience on the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-α2B for treating superficial bladder cancer, including patients failing previous BCG therapy. Thirty-two patients with superficial bladder cancer underwent 6 weekly treatments with full-, one-third, or one-tenth-dose of BCG plus 50 or 100 MU of IFN-α2B based on prior BCG exposure and tolerance. Patients with no evidence of disease proceeded onto maintenance therapy of 3 weekly treatments at 3 months followed by 2 additional maintenance cycles given 6 months apart. Response was assessed by cystoscopy/biopsy every 3 months after treatment. Before BCG plus IFN-α2B treatment, 20 patients (63%) had previously failed intravesical BCG therapy, 27 (84%) had aggressive disease (stage T1, grade 3, or carcinoma in situ), 27 (84%) had recurrent disease, 14 (44%) had multifocal disease, and 6 (19%) had disease of over 4 years duration. At median follow-up of 22 months, 21 patients (66%) remain disease-free and 11 patients (34%) had disease-recurrence. Nineteen of 32 patients (59%) were disease-free after the initial induction cycle. Six of 11 patients 55% ultimately failing combination therapy did so at the first 3 to 4 month evaluation. Four of 7 patients (57%) benefited from salvage re-induction therapy. Of the 20 patients previously treated with BCG, 12 patients (60%) remain disease-free. Combination BCG plus IFN-α2B intravesical therapy was well tolerated. Combination intravesical BCG plus IFN-α2B is an effective and tolerable alternative for patients with superficial bladder cancer, including those patients in whom intravesical BCG therapy had previously failed. Benefits of this combination therapy may include potentially less morbidity, improved clinical efficacy, and in the long term, fewer patients undergoing radical therapy. However, radical treatment options should be pursued for early failures of this combination regimen in those patients with risk factors for recurrence and progression. [Copyright &y& Elsevier]

: ObjectivesTo compare, in a single-surgeon, single-institution study, the efficacy of antegrade and retrograde endopyelotomy in terms of success rate and morbidity and to identify which risk factors affect treatment outcomes.: MethodsThe results were retrospectively reviewed for 88 patients with ureteropelvic junction obstruction treated with endopyelotomy. Antegrade endopyelotomy was performed with a hook knife, scissors, or cutting balloon device. Retrograde endopyelotomy was performed with a cutting balloon device. Objective results were based on intravenous urogram and/or diuretic nuclear renal scan findings, and subjective results were based on direct patient query and questionnaire.: ResultsNinety-three endopyelotomy procedures, 64 antegrade and 29 retrograde, were performed. The mean follow-up was 37.0 months (range 5 to 76). The overall success rates between antegrade and retrograde endopyelotomy (81.3% versus 75.9%) were not statistically different (P = 0.553). Patients with massive hydronephrosis and poor initial renal function were less likely to have successful endopyelotomy. Antegrade endopyelotomy, however, was more successful than retrograde endopyelotomy in patients with massive hydronephrosis (66.7% versus 20.0%; P = 0.046). The average operative time for antegrade and retrograde endopyelotomy was 93.9 and 32.7 minutes (P <0.001), respectively. The average length of hospital stay after antegrade and retrograde endopyelotomy was 3.20 and 0.14 nights (P <0.001), respectively.: ConclusionsBoth antegrade and retrograde endopyelotomy are effective treatments for ureteropelvic junction obstruction associated with minimal morbidity. Antegrade endopyelotomy appears to be more successful in patients with high-grade hydronephrosis. Retrograde endopyelotomy results in a shorter hospital stay, a shorter operative time, and less postoperative pain. [Copyright &y& Elsevier]

: ObjectivesTo evaluate the safety and efficacy of finasteride 5 mg during a 10-year period in men with enlarged prostates from a single center who participated in the double-blind and extension phases of the multicenter, Phase III, North American benign prostatic hyperplasia (BPH) trial. It is important that the long-term safety and efficacy of drugs intended for chronic administration in men with BPH be well understood.: MethodsThe Phase III North American BPH trial involved a 1-year, placebo-controlled, double-blind study, followed by a 5-year open extension with finasteride 5 mg/day. The trial enrolled men with symptomatic BPH, an enlarged prostate on digital rectal examination, and no evidence of prostate cancer. Of the 46 patients originally enrolled from our institution, 43 were randomized to receive finasteride or placebo, of whom 41 (95%) completed the double-blind study and entered the 5-year extension. Thirty (73%) of these 41 patients completed the 5-year extension. Patients continued to be followed up by their physicians for an additional 5 years, for a total follow-up of at least 10 years.: ResultsTwenty-four (56%) of the original 43 patients randomized to finasteride or placebo were judged as successfully treated during the 10-year finasteride follow-up (17 patients taking finasteride alone at 10 years and 7 patients who were taking finasteride alone when they discontinued during the 10-year follow-up for reasons not related to finasteride treatment). Altogether, 22 (51%) of the original 43 randomized patients continued finasteride treatment at 10 years (17 taking finasteride alone, 4 taking finasteride plus an alpha-blocker, and 1 taking finasteride for treatment of hematuria). Finasteride was well tolerated, with no new adverse experiences occurring with increasing duration of exposure to the drug.: ConclusionsThis long-term follow-up study has demonstrated that appropriately selected patients with symptomatic BPH and enlarged prostates are likely to have a long-term response to taking finasteride 5 mg daily. [Copyright &y& Elsevier]

Large renal stone burdens within a nondilated collecting system in patients with a relative contraindication to percutaneous nephrolithotomy can be a challenging problem. We describe a novel technique using a ureteral access sheath combined with extracorporeal shock wave lithotripsy to facilitate passage of stone fragments in such patients. [Copyright &y& Elsevier]

Objectives: Carbonic anhydrase-IX (CA-IX) is a cell surface tumor-associated antigen expressed by most clear cell renal cell carcinomas (RCCs). The specificity and the prognostic value of CA-IX provide impetus to create a mouse model of CA-IX-expressing RCC for testing CA-IX-targeted therapies against RCC. Methods: A retrovirus encoding the human CA-IX gene was used to transduce the murine RCC line, RENCA. In vivo growth kinetics and CA-IX expression were compared between RENCA and RENCA/CA-IX using heterotopic, metastatic, and orthotopic models. Results: Transduction of RENCA created the RENCA/CA-IX line with nearly 100% CA-IX surface expression. In the heterotopic model, subcutaneous injection of 500,000 and 50,000 cells led to tumor formation at 2 to 2.5 weeks after injection, with similar growth kinetics between the two cell lines at either cell number. In the pulmonary metastatic model, a similar number of metastases was noted after inoculation of RENCA and RENCA/CA-IX. In the orthotopic model, autopsy revealed a CA-IX-expressing renal tumor, as well as CA-IX-expressing metastases to the lungs, liver, contralateral kidney, intestines, and lymph nodes. In all the above models, the RENCA/CA-IX tumors retained expression of CA-IX, as demonstrated by immunohistochemistry staining. Conclusions: RENCA/CA-IX is the first tumor model that manifests in immunocompetent Balb/c mice and stably expresses a defined kidney cancer-associated antigen. It maintains antigen expression, forms metastases, and produces reliable tumor growth kinetics equivalent to that of its parental cell line. [ABSTRACT FROM AUTHOR]

Objectives: To determine, in a prospective study, the prostate-specific antigen (PSA) response to finasteride challenge in men with a serum PSA greater than 4 ng/mL who had undergone previous biopsy. Patients with a serum PSA level greater than 4 ng/mL who have undergone repeated prostate biopsy with prostate cancer (CaP) that was not detected present a diagnostic dilemma. The magnitude of PSA reduction after administration of finasteride has been well documented. In addition, doubling of the PSA value after 1 year of finasteride has been touted to be a more useful paradigm for diagnosing CaP than PSA alone.Methods: Thirty-eight men with a baseline serum PSA level greater than 4 ng/mL and a normal digital rectal examination who had been previously biopsied a minimum of two times, with CaP not detected, were given 5 mg finasteride daily. The PSA level was measured at 6 and 12 months with repeat transrectal ultrasonography and biopsy (12 cores) performed at 1 year. Changes in prostate volume, serum PSA, PSA density, and the incidence of CaP at 1 year were assessed.Results: The mean age of the group was 60.5 years (+/-7.6). For the group, the average number of previous biopsies performed was 2.9 (range 2 to 6). The baseline PSA level for the entire group was 6.32 ng/mL (+/-3.2), and the baseline prostate volume was 37.3 cm3 (+/-12.4). At 1 year, the PSA level had decreased to 3.73 ng/mL (-41.0%), and the prostate volume had decreased to 30.4 cm3 (-18.5%). In the 11 men (29%) in whom CaP was detected, the serum PSA decreased from 7.3 to 5.2 ng/mL (-28.8%) and the prostate volume decreased from 37.3 to 32.3 cm3 (-13.4%). CaP was detected in 0 of 10 men with a serum PSA decrease of 50% or higher, in 6 (32%) of 19 men with a PSA decrease between 33% and 50%, and in 5 (56%) of 9 men who had a PSA decrease of less than 33%.Conclusions: The data in this preliminary study suggest that the magnitude of change in serum PSA after 1 year of finasteride challenge may be useful in diagnosing CaP in patients with elevated PSA levels and prior negative prostate biopsy. [ABSTRACT FROM AUTHOR]