Ulrike Zwergel

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.

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

BackgroundThis 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.MethodsThe 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.ResultsCecropin 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 μg/ml and 220.05 μg/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.ConclusionCecropin 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.

Long-Term Results following Transurethral Resection of the Prostate

Two subsets of a single-center study population with benign prostatic hyperplasia (n(1) = 232; n(2) = 214) undergoing transurethral resection (TUR) of the prostate (TURP 1979 and 1995) entered a retrospective study designed to examine the long-term follow-up. The actual data were assessed with a patient-addressed questionnaire. Preoperative voiding patterns did not differ significantly; postoperative micturition revealed comparable results for both groups. Mortality and TUR syndrome rates were reduced to very low levels. The most significant improvement was found in blood transfusions. The postoperative incidence of urethral stricture (1.7 vs. 1.5%) or bladder neck contracture (2.7 vs. 2.4%) were low and did not alter significantly. Urinary incontinence changed for both collectives (11.4 vs. 3.3%). Urodynamic investigations revealed that all (n = 21) but 1 of the patients with TURP 1979 had the incontinence due to different bladder dysfunctions, but not because of postoperative stress incontinence. The questionnaire about the patient’s actual contentment after TURP 1979 showed 79% of the patients still satisfied, 12% neutral and 9% dissatisfied with their micturition. Overall the patients reported a generally favorable view of TURP outcome in the long-term follow-up.

Results and clinical management of extracorporeal piezoelectric lithotripsy (EPL) in 1321 consecutive treatments

SummaryThe Piezolith 2200 uses piezoelectrically generated high-energy sonic pulses for extracorporeal urinary stone disintegration. The generator is self-focussing. Calculi as small as 1 mm in diameter can be localized by an integrated ultrasound location system. As treatment with the Piezolith does not cause any pain, patients are treated without anesthesia and without analgesia. Considering that cardiac arrhythmia does not occur with the piezoelectric equipment, the procedure is preferred for treatment of high-risk cardiac patients. Since the lithotriptor consists of a special mobile table with an opening in the surface to apply shock waves, the correct focus-position for lithotripsy can be found without difficulty, even in obese or small patients, or those with skeletal deformations.From January 1986 to August 1987, 740 patients representing 764 renal units were successfully treated. A total of 710 calculi (92.9%) were located in the kidney; the rest (7.1%) consisted in stones of the upper and lower ureter treated in situ. To reduce post-therapy auxiliary procedures, internal stents are applied retrogradely in all calculi larger than 15 mm.

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.

Effects of Prostaglandins and Prostaglandin Synthetase Inhibitors on Acutely Obstructed Kidneys in the Dog

An intact canine model was developed to study the effects of prostaglandins (PG) and prostaglandin synthetase inhibitors on acutely obstructed kidneys. Totally implanted nephrostomy tubes were placed to measure renal pelvic pressure. Complete ureteral obstruction was obtained with a Fogarty balloon catheter inflated in the distal ureter; by this method renal pelvic pressure reached 40-50 mm Hg. Renal pelvic pressure was reduced after intravenous indomethacin and dipyrone administration, whereas blood pressure showed no major changes. Exogenous prostaglandins had both immediate and contrary effects: PGE2 caused a significant decrease, whereas PGF2 alpha caused a significant increase in renal pelvic and blood pressure. The reduced rise in renal pelvic pressure appears to be the main reason for the analgesic effects of prostaglandin synthetase inhibitors. The efficiency of these drugs in the treatment of renal colic is supported by this study, that of prostaglandins cannot be proved.

Effects of prostaglandin synthetase inhibitors on the upper urinary tract

SummaryProstaglandin inhibitors such as indomethacin have been used for the treatment of renal colic. While opioids have a central analgesic effect, the effects of indomethacin are mainly peripheral, acting directly on the kidney. Pharmacourodynamic investigations of the upper urinary tract in men have demonstrated that intravenous indomethacin reduces renal pelvic pressure. These effects are more intense with indomethacin than with metamizol and are not found with hyoscine butylbromide. We have determined that indomethacin reduces the smooth muscle activity of human renal pelvis preparations in a tissue bath. These findings may represent a further possible direct effect of indomethacin on the upper urinary tract during the treatment of renal colic.

Aktuelle konservative Behandlung einer Nierenkolik

ZusammenfassungProstaglandinsynthesehemmer und Parasympatholytika werden oft zur Schmerzbehandlung von Nierenkoliken verwendet. Welche Wirkung und Bedeutung diese Medikamente bei der analgetischen Therapie haben, soll diskutiert werden. Am akut gestauten oberen Harntrakt des Hundes und des Menschen konnte mit Indometacin und mit Metamizol der Nierenbeckendruck signifikant gesenkt werden. Für das Parasympatholytikum N-Butylscopolamin konnte dieser Nachweis der Drucksenkung im Nierenbecken nicht geführt werden. Mit Prostaglandinsynthesehemmern werden die für die Analgesie notwendigen Effekte der Drucksenkung erzielt; damit wird die Verwendung dieser Medikamente zur Kolikbehandlung untermauert. Mit N-Butylscopolamin wird demgegenüber der erhöhte intrapelvine Druck nicht beseitigt, so daß dessen Einsatz bei der Nierenkoliktherapie bezweifelt werden muß.AbstractProstaglandin synthesis inhibitors and parasympatholytic drugs are often used as analgetics in the case of renal colic. This paper analyzes how and whether these drug effects are important for the analgetic therapy. In an animal and in a human model with acutely obstructed kidneys we found that intravenous application of Indometacine and dipyrone significantly reduces renal pelvic pressure. The parasympatholytic drug hyoscine butylbromide did not produce any change of upper urinary tract dynamics. Inhibitors of prostaglandin synthesis thus effect pressure reduction in the renal pelvis, which is necessary for analgetic therapy. In contrast, hyoscine butylbromide does not have any influence on the acute upper urinary tract obstruction; consequently its usefulness in the treatment of renal colic is rather doubtful.

Results in the Use of Extracorporeal Piezoelectric Lithotripsy (EPL) for Treatment of Urinary Calculi

The Piezolith 2200 as an extracorporeal shock wave lithotripter uses piezoelectrically generated, high-energy sonic impulses for treatment of urinary calculi; the shock wave generator is self-focussing. Localization of concrements is performed by means of ultrasound imaging. Treatment with the Piezolith 2200 is painless for the patient and thus possible without anesthesia and analgesia. We report on 806 cases of treatment involving a total of 572 kidneys in 567 patients (561 adults, 6 children) suffering from calculi of various sizes in the renal pelvis (n = 126), calculi in the calyces (n = 384), partial (n = 24) or full (n = 19) staghorn calculi, as well as calculi in the upper part of the ureter (n = 19). In 88% of these cases the concrements could be removed completely. Since cardiac activity is not influenced by piezoelectrically generated high-energy impulses, this procedure is particularly suited to the treatment of patients with heart problems.

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.