Important aspects of organ-preserving surgery for renal tumors: indications, new standards, and oncological outcomes.

INTRODUCTION: Organ-preserving surgery for renal tumors has become more common over the past two decades. At first, part of the kidney, rather than all of it, was resected only if there was an absolute indication for doing so, i.e., if the tumor was located in an anatomically or functionally solitary kidney or if renal failure was already present. Now that favorable oncological outcomes have been demonstrated, renal tumors are increasingly often removed with only partial resection of renal tissue even when the indications are less stringent, including when the other kidney is healthy. METHODS: The indications for, and oncological outcomes of, partial renal resection are presented and discussed on the basis of a selective literature search of Medline as well as the guidelines of the European Association of Urologists (EAU). RESULTS AND CONCLUSIONS: The EAU, in its new guidelines for renal cell carcinoma, recommends partial renal resection as the standard treatment for tumors less than 4 cm in size that are wholly contained within one kidney when the other kidney is healthy. This practice yields comparable outcomes to those of nephrectomy, with tumor-specific five-year survival rates exceeding 90%. In major urological centers, partial resection is favored even for tumors larger than 4 cm, as long as they are in a favorable location. Nonetheless, the estimated rate of nephrectomy for tumors less than 4 cm in size currently remains very high in Germany, as it does in American studies, even though the organ-preserving resection of such small tumors usually results in cure.

Medical therapy to facilitate the passage of stones: what is the evidence?

CONTEXT: Medical expulsive therapy (MET) for urolithiasis has gained increasing attention in the last years. It has been suggested that the administration of alpha-adrenoreceptor antagonists (alpha-blockers) or calcium channel blockers augments stone expulsion rates and reduces colic events. OBJECTIVE: To evaluate the efficacy and safety of MET with alpha-blockers and calcium channel blockers for upper urinary tract stones with and without prior extracorporeal shock wave lithotripsy (ESWL). EVIDENCE ACQUISITION: A systematic review of the literature was performed in Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews searched through 31 December 2008 without time limit. Efficacy and safety end points were evaluated in 47 randomised, controlled trials assessing the role of MET. Meta-analysis was conducted using Review Manager (RevMan) v.5.0 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). EVIDENCE SYNTHESIS: Pooling of alpha-blocker and calcium channel blocker studies demonstrated a higher and faster expulsion rate compared to a control group (risk ratio [RR]: 1.45 vs 1.49; 95% confidence interval [CI]: 1.34-1.57 vs 1.33-1.66). Similar results have been obtained after ESWL (RR: 1.29 vs 1.57; 95% CI: 1.16-1.43 vs 1.21-2.04). Additionally, lower analgesic requirements, fewer colic episodes, and fewer hospitalisations were observed within treatment groups. CONCLUSIONS: Pooled analyses suggest that MET with alpha-blockers or calcium channel blockers augments stone expulsion rates, reduces the time to stone expulsion, and lowers analgesia requirements for ureteral stones with and without ESWL for stones < or = 10 mm. There is some evidence that a combination of alpha-blockers and corticosteroids might be more effective than treatment with alpha-blockers alone. Renal stones after ESWL also seem to profit from MET. The vast majority of randomised studies incorporated into the present systematic review are small, single-centre studies, limiting the strength of our conclusions. Therefore, multicentre, randomised, placebo-controlled trials are needed.

Combining 153Sm-lexidronam and docetaxel for the treatment of patients with hormone-refractory prostate cancer: first experience.

PURPOSE: 153Sm-lexidronam has been used for the palliation of symptoms from painful bone metastases for years, while docetaxel has recently been shown to improve the survival of patients with hormone-refractory prostate cancer (HRPC). The first clinical experience with the combination of both treatment modalities is reported. METHODS: Between 2005 and 2006, 12 patients with muliple bone metastases from HRPC were treated with a single application of 37 MBq/kg body weight 153Sm-lexidronam and 6 weekly infusions of 35 mg/m2 docetaxel. Data on survival, prostate-specific antigen (PSA) response, symptom palliation, toxicity, and scintigraphic follow-up are provided. RESULTS: Mean follow-up was 11.4 (range, 1.1-25.8) months, overall 1-year survival was 48.6%, and median survival was 11.5 months. A PSA response of >50% was documented in 50% of patients. The average pain score (visual analog scale: 1-10) was reduced from 5.1 to 1.4 (p = 0.016) with decrease of > or =2 in 58.3% of patients. The average World Health Organization medication level dropped from 1.6 to 1.1 (p = 0.5). Overall toxicity was moderate, but 1 patient died due to neutropenic sepsis. CONCLUSIONS: Our analysis demonstrates feasibility and therapeutic potential for the combination treatment and merits prospective investigation. Further studies will be planned with respect to the potentially synergistic hematologic toxicity of bone-seeking radiopharmaceuticals and chemotherapy.

Antimicrobial peptides of the Cecropin-family show potent antitumor activity against bladder cancer cells.

BACKGROUND: This study evaluated the cytotoxic and antiproliferative efficacy of two well-characterized members of the Cecropin-family of antimicrobial peptides against bladder tumor cells and benign fibroblasts. METHODS: The antiproliferative and cytotoxic potential of the Cecropins A and B was quantified by colorimetric WST-1-, BrdU- and LDH-assays in four bladder cancer cell lines as well as in murine and human fibroblast cell lines. IC50 values were assessed by logarithmic extrapolation, representing the concentration at which cell viability was reduced by 50%. Scanning electron microscopy (SEM) was performed to visualize the morphological changes induced by Cecropin A and B in bladder tumor cells and fibroblasts. RESULTS: Cecropin A and B inhibit bladder cancer cell proliferation and viability in a dose-dependent fashion. The average IC50 values of Cecropin A and B against all bladder cancer cell lines ranged between 73.29 mug/ml and 220.05 mug/ml. In contrast, benign fibroblasts were significantly less or not at all susceptible to Cecropin A and B. Both Cecropins induced an increase in LDH release from bladder tumor cells whereas benign fibroblasts were not affected. SEM demonstrated lethal membrane disruption in bladder cancer cells as opposed to fibroblasts. CONCLUSION: Cecropin A and B exert selective cytotoxic and antiproliferative efficacy in bladder cancer cells while sparing targets of benign murine or human fibroblast origin. Both peptides may offer novel therapeutic strategies for the treatment of bladder cancer with limited cytotoxic effects on benign cells.

Outcome of prostate cancer patients with initial PSA> or =20 ng/ml undergoing radical prostatectomy.

OBJECTIVES: To retrospectively assess the outcome of patients with initial PSA of 20 ng/ml or higher undergoing radical prostatectomy (RP) for prostate cancer (pCA). METHODS: Between January 1986 and June 2005, 275 patients with preoperative PSA> or =20 ng/ml underwent RP for pCA at our institution. Overall, disease-specific and biochemical progression-free survival rates for the entire cohort and for particular subgroups were determined. RESULTS: Median patient age at time of surgery was 64 yr (range: 44-75). Fifty-seven patients (20.7%) had pT2 stage, 206 (74.9%) pT3, and 10 (3.7%) pT4; 78 (28.4%) presented with local nodal metastases (pN+). To date, 40 patients have died (14.5%), 22 of pCA and 18 of other causes. Biochemical progression occurred in 92 patients (33.5%). Overall (and disease-specific) survivals at 5, 10, and 15 yr were 87% (93%), 70% (83%), and 58% (71%), respectively. These survival rates did not significantly differ between patients receiving immediate versus deferred hormonal therapy (in case of progression). Five-year PSA progression-free survival in patients on surveillance (receiving deferred hormonal treatment at the onset of rising PSA values) was 53%. For patients on immediate hormonal treatment following RP, the 5-yr hormone-refractory PSA progression rate was 76%. CONCLUSIONS: According to long-term follow-up results in this high-risk cohort of patients with preoperative PSA> or =20 ng/ml, RP can be considered a viable therapeutic option. With regard to combining immediate hormonal therapy with surgery, the optimal treatment following RP remains to be defined.

Transitional cell carcinoma of the ureter: prognostic factors influencing progression and survival.

OBJECTIVES: We retrospectively evaluated prognostic factors for progression-free and disease-specific survival in a large cohort of patients with transitional cell carcinoma (TCC) of the ureter. METHODS: A single-centre series of 145 consecutive patients treated with partial resection of the ureter or nephroureterectomy between 1975 and 2004 was evaluated. Median follow-up was 96 mo. Routine preoperative laboratory parameters as well as clinical and tumour-specific data were assessed. Univariate and multivariate statistical analyses were performed. RESULTS: Five-year disease-specific survival ranged from 96.1% for stages pTa to 28.6% for pT4. Grade1 tumours were associated with 5-yr disease-specific survival rates of 100% compared with 84% for G2, and 51.9% for G3 tumours, respectively. Univariate analyses identified pT stage and grade, tumour diameter, cM and pN categories, weight loss, the presence of synchronous tumour in the renal pelvis as well as elevated levels for humoral factors such as serum alkaline phosphatase (AP), white blood cell (WBC) count, platelet count, gamma-glutamyl transferase, creatinin, and blood urea nitrogen as prognostic factors. In multivariate analyses, tumour grade and WBC counts were predictive for low progression-free survival rates, whilst simultaneous tumour in the renal pelvis, high AP levels, and WBC counts were correlated with worse disease-specific survival. CONCLUSIONS: Our retrospective analysis provides clinical factors to identify patients with TCC of the ureter at high risk for progression and death of disease. Interestingly, humoral factors such as elevated serum AP levels and high WBC counts were demonstrated to be of paramount prognostic significance besides tumour stage, grade and multifocality.

Long-term survival under maintenance gemcitabine chemotherapy for metastatic transitional cell carcinoma.

We report a case of a 74-year-old patient who received 41 courses of maintenance therapy with gemcitabine over a length of 28 months for metastatic transitional cell carcinoma. One year earlier the patient had received three cycles of adjuvant cisplatin-based combination chemotherapy after nephro-ureterectomy for a locally advanced urothelial cancer of the right renal pelvis. This case demonstrates a paradigm shift in the palliative treatment of advanced urothelial cancer, with the implementation of more tolerable agents such as gemcitabine. Even elderly patients with impaired renal function may benefit in terms of tumor reduction and survival from systemic chemotherapy, which may be applied over a prolonged period of time.

Lymph node positive prostate cancer: long-term survival data after radical prostatectomy.

PURPOSE: We retrospectively reviewed the outcome in our patients with prostate cancer and regional positive lymph nodes who underwent prostatectomy. MATERIALS AND METHODS: Between January 1984 and December 2002, 147 men were found to have local lymph node metastases after surgery, of whom 135 underwent further androgen ablation, including 88% within 6 weeks after prostatectomy. We especially determined overall, cancer specific and progression-free survival rates. RESULTS: Median patient age was 63.2 years (range 46 to 75 years). Postoperative followup was up to 214 months (median 41.9). There was 1 death secondary to surgery. To date 49 patients (33.3%) had disease progression, including 6 with a prostate specific antigen increase later than 100 months after surgery, and 36 (24.5%) died, including 22 of prostate cancer and 14 of other causes. Overall and cause specific survival probabilities at 5, 10 and 15 years were 76.6% and 86.5%, 60.1% and 73.7%, and 47.2% and 57.9%, respectively. Median overall survival was 144 months and median cancer specific survival was greater than 145 months. Overall progression-free probabilities at 5, 10 and 15 years were 72.7%, 49.8% and 31.6%, respectively. Biochemical progression-free survival rates were 77.4% after 5, 53.0% after 10 and 33.7% after 15 years. CONCLUSIONS: Since three-quarters of our patients were likely not to die of prostate cancer within the 10 years after surgery despite histological evidence of lymph node metastases, radical prostatectomy with or without hormonal therapy is a viable option for patients with local lymph node involvement, particularly in view of long-term survival.