[Update of the 2Sk guidelines on the diagnostics, treatment and metaphylaxis of urolithiasis (AWMF register number 043-025) : What is new?] / Aktualisierung der S2k-Leitlinie zur Diagnostik, Therapie und Metaphylaxe der Urolithiasis (AWMF Registernummer 043-025) : Was ist neu?

The increase of medical knowledge and technical innovations together with the demographic change represent a challenge for the new conception of guidelines and clinical studies. The present S2k guidelines, which are exclusively concerned with kidney and ureteral stones, should support the treatment of urolithiasis in hospitals and private practices and provide information on urolithiasis for patients. Increasing interdisciplinary collaboration in stone treatment is also demonstrated in the number of professional and working groups participating in the update of the new guidelines. The present S2k guidelines emerged from a consensus process and demonstrate the current recommendations in step with actual practice. They provide decision-making guidance for diagnostics, treatment and metaphylactic measures based on expert opinions and available published fundamental evidence from the literature.

[Recurrence prevention of urolithiasis with respect to economic aspects]. / Rezidivprävention der Urolithiasis unter Berücksichtigung ökonomischer Aspekte.

Recurrence prevention in urinary stone disease not only makes good medical but also economic sense. Up to 40% of recurrences can be prevented by a rational urinary stone metaphylaxis whereby not only treatment costs but also the cost of lost productive work time can be saved. Detailed knowledge of stone composition and medical history of the patient is a prerequisite for a rational metaphylaxis which according to the S2 guidelines results in assignment to the high or low risk group. The required diagnostic and therapeutic measures are also decided by this classification. In addition to general metaphylaxis (reduction of overweight, physical activity, appropriate fluid intake, balanced diet) further specific measures may be necessary depending on the risk group and stone type.

Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99].

BACKGROUND: The second-line chemotherapeutic treatment for metastatic urothelial cancer (UC) after failure of cisplatin-based first-line therapy needs to be improved. Based on encouraging phase II data of gemcitabine and paclitaxel (Taxol) (GP), this trial was designed to compare a short-term (arm A) versus a prolonged (arm B) second-line combination chemotherapy of GP. PATIENTS AND METHODS: Of 102 randomized patients, 96 were eligible for analysis. Primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rates (ORR) and toxicity. RESULTS: Neither OS [arm A: 7.8 (95% CI: 4.2-11.4), arm B: 8.0 (95% CI: 4.9-11.1) months] and PFS [arm A: 4.0 (95% CI: 0-8.0), arm B: 3.1 (95% CI: 1.9-4.2) months] nor ORR (arm A: 37.5%, arm B: 41.5%) were significantly different. On prolonged treatment, more patients experienced severe anemia (arm A: 6.7% versus arm B: 26.7% grade III/IV anemia; P = 0.011). In six patients, treatment was stopped during the first cycle due to disease progression or toxicity. Two patients died due to treatment-related toxic effects. CONCLUSION: Due to rapid tumor progression and toxicity at this dosage and schedule in a multicenter setting, it was not feasible to deliver a prolonged regimen. However, a high response rate of ∼40% makes GP a promising second-line treatment option for patients with metastatic UC.

Change in the fatty acid pattern of erythrocyte membrane phospholipids after oral supplementation of specific fatty acids in patients with gastrointestinal diseases.

BACKGROUND/OBJECTIVES: The fatty acid pattern of membrane phospholipids is suggested to affect membrane fluidity and epithelial barrier function as a result of membrane fatty acid unsaturation. The incorporation of n-3 polyunsaturated fatty acids (PUFAs) into membrane phospholipids may diminish inflammatory potential in patients with gastrointestinal diseases. The aim of this study was to improve the fatty acid profile of erythrocyte membrane phospholipids after oral supplementation of specific fatty acids in patients with maldigestion and/or malabsorption. SUBJECTS/METHODS: We conducted a randomized, double-blind, controlled trial. A total of 48 patients with gastrointestinal diseases received either fat-soluble vitamins A,D,E,K (ADEK) or ADEK plus fatty acids alpha-linolenic acid (ALA), docosahexaenoic acid (DHA) and medium-chain triglycerides (FA-ADEK) for 12 weeks. The fatty acid profile of erythrocyte membrane phospholipids, dietary intake, plasma antioxidant vitamins and serum gamma-glutamyl transferase (GGT) were evaluated at baseline, 8 and 12 weeks after supplementation. RESULTS: Supplementation with FA-ADEK increased ALA, DHA and eicosapentaenoic acid (EPA) concentrations of erythrocyte membrane phospholipids by 0.040, 1.419 and 0.159%, respectively, compared with ADEK supplementation (-0.007, 0.151 and 0.002%, respectively) after 12 weeks (all P

[Results of the randomised phase III study of the German Testicular Cancer Study Group. Retroperitoneal lymphadenectomy versus one cycle BEP as adjuvant therapy for non-seminomatous testicular tumours in clinical stage I]. / Ergebnisse der randomisierten Phase-III-Studie der "German Testicular Cancer Study Group". Retroperitoneale Lymphadenektomie vs. 1 Zyklus PEB als adjuvante Therapie beim nichtseminomatösen Hodentumor im klinischen Stadium I.

OBJECTIVE: As 30% of non-seminomas in clinical stage I will progress during active surveillance, alternative adjuvant strategies of 2 cycles of bleomycin, etoposid, cisplatin (BEP) or nerve sparing retroperitoneal lymphadenectomy (RPLND) can be offered. The risk of relapse is reduced to 2% and 10%, respectively. Without prognostic markers and with lowered toxicity it is postulated that only one cycle of BEP could significantly reduce the recurrence rate in comparison to RPLND. MATERIALS AND METHODS: Between 1996 and 2005, 382 patients were randomly assigned to receive either RPLND (n=191) or 1 cycle of BEP (n=191). In accordance with the protocol, 174 patients were treated with 1 cycle of BEP and 173 underwent RPLND. The primary study end-point was a reduction of recurrence from 10% after RPLND to a maximum of 3% after 1 cycle of BEP. RESULTS: After a mean follow-up of 4.7 years, there were 2 and 13 recurrences in the according-to-protocol population with chemotherapy and surgery, respectively. The difference between chemotherapy (1.15%) and surgery (7.5%) was statistically significant (p=0.0033). The tumor-specific survival was 100%. CONCLUSION: This largest randomized trial investigating treatment strategies in clinical stage I non-seminomas (AUO AH 01/94) showed the superiority of one cycle BEP over RPLND. The data obtained represent the basis for a reduced chemotherapy.

[A critical assessment of phytotherapy for prostate cancer]. / Eine kritische Bewertung der Phytotherapie des Prostatakarzinoms.

Prostate cancer patients increasingly use complementary and alternative medicines to support the body's immune system in addition to conventional treatment to minimize morbidity associated with conventional treatment, to enhance the quality of life, and ultimately in the hope to cure cancer when conventional treatment fails. As there is a large variety of phytomedicines promoted as potential treatment for prostate cancer, the aim of this review was to differentiate between preventive and therapeutic approaches and evaluate which phytochemicals might be suited for therapy of prostate cancer. Therefore, preclinical in vitro and in vivo data as well as clinical trials with phytosubstances such as genistein, lycopene, epigallocatechin gallate, resveratrol, and mistletoe were assessed. The presented data show that at present there is no clinical evidence that phytochemicals might have a therapeutic use in prostate cancer in relation to reduction of tumor progression or improved survival. The question about an improved immune function or quality of life remains open. Potentially the use of phytochemicals could play a role in a preventive setting.

[Modern general metaphylaxis of stone disease. New risks, new evidence, new recommendations]. / Moderne allgemeine Harnsteinmetaphylaxe. Neue Risiken, neue Evidenz, neue Empfehlungen.

The prevalence and incidence of urolithiasis have markedly increased over the past several decades. Inappropriate dietary habits, overweight, and lifestyle are considered to be important risk factors for stone formation. The primary goal of metaphylaxis of stone disease is to correct the individual biochemical risk profile. A reduction in the risk of stone formation and recurrence rate can already be achieved by appropriate dietary treatment. One of the most effective dietary measures is a sufficient circadian fluid intake of suitable beverages. The reduction of overweight is suggested to additionally contribute to a decrease in the risk of recurrent stone formation.

Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with transitional cell carcinoma (AUO Trial AB 20/99).

The objectives are to evaluate and compare the response and toxicity of a 3-weekly and a 2-weekly regimen of gemcitabine (Gem) and paclitaxel (Pac) second-line treatment in patients with transitional cell carcinoma (TCC). Between June 2000 and July 2001, 30 patients with progressive disease (PD) during first-line chemotherapy (n = 11) or relapse after adjuvant cisplatin-based chemotherapy of a metastatic or locally advanced TCC (n = 18) have been randomised to receive either six cycles (schedule A) of 3-weekly Gem (1000 mg/qm, days 1 and 8) and Pac (175 mg/qm, day 1) or 2-weekly treatment until disease progression (schedule B) with Gem (1250 mg/qm, day 1) and Pac (120 mg/qm, day 2). Restaging was performed after every 6 weeks by clinical imaging. Of 30 patients, one patient in schedule A and two patients in schedule B were not evaluable for response due to serious adverse events (SAEs) during the first cycle. The overall objective response (OR) was 44% (12 of 27) with eight complete remissions (CRs) and four partial remissions. Median time to progression (TTP) was 11 (3-41) months in schedule A and 6 (1-15+) months in schedule B. Median survival was 13 (5-46) months in schedule A and 9 (0-16) months in schedule B. Schedule A showed a significantly higher rate of CRs (7 vs. 1, p < 0.05). With a median number of six (1-6) cycles (A) and nine (1-23) cycles (B), TTP and survival were not significantly different. In schedule B, one patient had WHO grade IV anaemia and leucopenia. WHO grade III toxicities were seen in schedule A/B as follows: anaemia 3 (23%)/2 (16%) patients, leucopenia 5 (38%)/2 (16%), thrombocytopenia 0/2 (16%) and alopecia 10 (76%)/4 (32%). The combination of Gem and Pac is an effective second-line regimen in patients with mainly poor prognosis due to PD after cisplatin-based chemotherapy. Except for three SAEs (uncertainly therapy related), both regimens were tolerated well. The 3-weekly schedule with a nonsplit Pac dose showed a significantly higher complete response rate in our small study population and, thus, might be superior to the 2-weekly schedule.

Influence of a mineral water rich in calcium, magnesium and bicarbonate on urine composition and the risk of calcium oxalate crystallization.

OBJECTIVE: To evaluate the effect of a mineral water rich in magnesium (337 mg/l), calcium (232 mg/l) and bicarbonate (3388 mg/l) on urine composition and the risk of calcium oxalate crystallization. DESIGN: A total of 12 healthy male volunteers participated in the study. During the baseline phase, subjects collected two 24-h urine samples while on their usual diet. Throughout the control and test phases, lasting 5 days each, the subjects received a standardized diet calculated according to the recommendations. During the control phase, subjects consumed 1.4 l/day of a neutral fruit tea, which was replaced by an equal volume of a mineral water during the test phase. On the follow-up phase, subjects continued to drink 1.4 l/day of the mineral water on their usual diet and collected 24-h urine samples weekly. RESULTS: During the intake of mineral water, urinary pH, magnesium and citrate excretion increased significantly on both standardized and normal dietary conditions. The mineral water led to a significant increase in urinary calcium excretion only on the standardized diet, and to a significantly higher urinary volume and decreased supersaturation with calcium oxalate only on the usual diet. CONCLUSIONS: The magnesium and bicarbonate content of the mineral water resulted in favorable changes in urinary pH, magnesium and citrate excretion, inhibitors of calcium oxalate stone formation, counterbalancing increased calcium excretion. Since urinary oxalate excretion did not diminish, further studies are necessary to evaluate whether the ingestion of calcium-rich mineral water with, rather than between, meals may complex oxalate in the gut thus limiting intestinal absorption and urinary excretion of calcium and oxalate.

Fluid intake and epidemiology of urolithiasis.

A low urine volume is an important risk factor in urinary stone formation. The present article summarizes available data from epidemiological and clinical studies to elucidate the impact of fluid intake and urine volume on the risk of urinary stone formation and the prevention of stone recurrence. A review of the literature shows that an increased urine volume achieved by a high fluid intake exerts an efficacious preventive effect on the onset and recurrence of urinary stones. A high water intake and urine dilution results in a marked reduction in saturation of lithogenous salts. The type of fluids should be carefully selected to achieve the appropriate change of urine composition depending on stone composition. A sufficient intake of fluid is one of the most important preventive measures for stone recurrence.

Gemcitabine monotherapy as second-line treatment in cisplatin-refractory transitional cell carcinoma - prognostic factors for response and improvement of quality of life.

OBJECTIVES: i) To evaluate objective response, toxicity, and quality of life (QoL) of gemcitabine monotherapy as second-line treatment in patients with cisplatin-refractory, metastatic transitional cell carcinoma (TCC). ii) To assess prognostic parameters for response to treatment and for improvement of QoL parameters. PATIENTS AND METHODS: 30 patients were prospectively enrolled in this open-label, nonrandomized multicenter phase II trial. Patients received up to 6 courses of gemcitabine monotherapy (1,250 mg/m(2) on day 1 and 8 of a 21-day course). 28 of 30 patients were available for response evaluation. RESULTS: Objective response (OR) was seen in 3/28 (11%) of patients (2 complete remissions, 1 partial remission). The mean time to progression (TTP) was 4.9 +/- 3.5 months and mean disease-specific survival time was 8.7 +/- 4.7 months. 13 of 28 patients did not progress (OR + 10 stable diseases), and TTP (8.0 +/- 2.7 months, p < 0.001) as well as survival time (10.2 +/- 3.8 months, p < 0.05) differed significantly from those who showed progressive disease within 18 weeks of treatment. Pain values significantly improved in the group of responders from 4.3 +/- 1.9 to 5.8 +/- 1.3 points (p < 0.05). Response to cisplatin pretreatment was the best prognosticator for the response to gemcitabine. CONCLUSIONS: Gemcitabine monotherapy as second-line treatment is justified in patients with metastatic TCC who are refractory to cisplatin treatment. Patients with initially OR to cisplatin benefit most from second-line treatment. QoL remains stable during treatment, and pain improves especially in patients with bone metastases.

Urinary oxalate excretion in female calcium oxalate stone formers with and without a history of recurrent urinary tract infections.

Therapy with antibiotics in recurrent urinary tract infections may destroy colonies of Oxalobacter formigenes in the intestinal tract. A lack of oxalate degradation caused by the absence of this bacterium is suggested to contribute to the hyperabsorption of dietary oxalate and to the increase in urinary oxalate excretion. The present study was performed to evaluate the effect of recurrent urinary tract infections and subsequent changes induced in the urinary excretion profile in female calcium oxalate stone formers. Serum biochemical profiles, 24-h urinary parameters, and the personal characteristics of 57 female calcium oxalate stone patients with recurrent urinary tract infections (RUTI) were compared with 78 female calcium oxalate stone patients without a history of urinary tract infection. All subjects were recruited during the same period. In female patients with RUTI, urinary oxalate excretion was significantly higher (0.374 mmol/day) than in females without urinary tract infection (0.308 mmol/day) (P < 0.05). Moreover, the mean 24-h pH value and urinary sodium excretion were significantly higher in women with RUTI than in women without a history of urinary tract infection. The significantly higher urinary oxalate excretion in female calcium oxalate stone formers with recurrent urinary tract infections may be associated with the application of antibiotics and a subsequent temporary or permanent decolonization of Oxalobacter formigenes.

Calcium-binding capacities of different brans under simulated gastrointestinal pH conditions. In vitro study with (45)Ca.

The present study was performed to investigate calcium-binding characteristics of different brans under simulated gastrointestinal pH conditions and to explore the significance of dietary fiber, oxalate, and phytate for calcium binding. Different brans (rice, rye, soy, fine wheat, coarse wheat, and oat) and CaCl(2) solution containing (45)Ca were incubated at 37 degrees C at gastric pH (2.2) followed by buffering steps of 1 degree from pH 3.0 to pH 8.0. Total calcium binding and calcium-binding capacity of the pH 2.2 soluble bran fraction were determined. Additionally, oxalate and phytate contents of brans and solubility profiles of phytic acid were investigated. Calcium-binding capacities of brans showed a clear pH dependence. At gastric pH calcium binding was low in all brans, ranging from 0.022 to 0.040 mmol of calcium/g of bran. Soy bran, nearly phytate-free, showed higher binding values up to pH 4.0 and lower values between pH 5.0 and 8.0. In all other brans, binding values increased strongly with increasing pH in the quantitative order rice bran > coarse wheat bran > fine wheat bran > rye bran > oat bran. The solubility profiles indicate that in the cases of rye, wheat, and rice bran phytate accounts for 70-82% of their total calcium-binding capacities. The results suggest that dietary fiber makes no important contribution to calcium binding, except for soy and oat brans. Oxalate plays only a minor role in calcium binding by brans.

Adjuvant chemotherapy in stage I and stage II testicular cancer.

Adjuvant chemotherapy in low-stage testis cancer is an accepted treatment option for two clinical situations: (1) chemotherapy after complete removal of the primary tumor by orchidectomy without clinical evidence of metastasis (clinical stage I), and (2) chemotherapy after complete surgical removal of non-seminomatous retroperitoneal metastases up to 5 cm in greatest transverse diameter by retroperitoneal lymph node dissection in clinical stage II. Aim of treatment is the prevention of tumor recurrences. The risk of recurrence depends on the type and stage of disease and ranges from 16% (clinical stage I seminoma) to 50% (pathological stage II B non-seminoma). Thus, 50-84% of patients receive adjuvant treatment unnecessarily. Prognostic factors have been developed in each tumor entity to tailor treatment to patients with high risk of recurrence.

Risk factors for relapse in stage I non-seminomatous germ-cell tumors: preliminary results of the German Multicenter Trial. German Testicular Cancer Study Group.

Risk factor analysis to identify low-risk patients for occult metastatic disease (vascular invasion, percentage embryonal carcinoma, MIB-I proliferation rate) yields reliable results if performed by experts. A correct prediction is possible at the 90% level. Similar accuracy, however, may be achieved if the computed tomography (CT) staging is optimized and the evaluation performed by an experienced investigator. The combination of both methods (biological risk factor analysis and CT staging) may virtually exclude the risk of relapse in a limited number of patients. However, so far, no risk factor that is able to reliably predict occult metastatic disease or relapse in clinical state I patients has been identified in prospective trials. The preliminary results of the current German Multicenter Trial suggest an inferior value of prediction for low-risk patients if risk factor analysis and/or CT staging is performed in non-specialized centers.

Current aspects of epidemiology and nutrition in urinary stone disease.

Current examples for the development of urinary stone disease are discussed by means of data from the literature and our own studies. Urinary stone disease has gained increasing significance due to changes in living conditions, i.e., industrialization and malnutrition. Changes in prevalence and incidence, the occurrence of stone types and stone location, and the manner of stone removal are explained. The importance of nutrition in the prevention of calcium oxalate stone disease is discussed in terms of fluid intake, calcium and oxalate metabolism, and dietary fat intake. The results of a study on a standardized mixed diet or an ovo-lactovegetarian diet show that well-balanced nutrition with consecutive high intake of fluids leads to a significant decrease in the risk for urinary stone formation (calculated as relative supersaturation with calcium oxalate by the computer program EQUIL).

Influence of a mixed and a vegetarian diet on urinary magnesium excretion and concentration.

Urinary Mg is suggested to be an effective inhibitor of the formation and growth of calcium oxalate stones. In order to examine the influence of variations in dietary Mg on urinary Mg excretion, ten healthy male subjects were kept on two different standard diets for 5 d each. In the course of the test period, 24 h urine samples were collected. Diets 1 and 2 were calculated according to the dietary recommendations of the German Society of Nutrition (Deutsche Gesellschaft für Ernährung, 1986). Diet 1 was established as a model of a balanced mixed diet, whereas diet 2 represented an ovo-lacto-vegetarian meal plan. Diets 1 and 2 were isoenergetic with equal amounts of the main nutrients, estimated from food tables, and a constant fluid intake. In contrast to the content of Mg (336 mg) and dietary fibre (28 g) of diet 1, diet 2 was rich in Mg (553 mg) and dietary fibre (52 g). On the ingestion of diet 1, renal Mg excretion was 5.09 (SEM 0.35) mmol on the control day and increased slightly but not significantly to 5.40 (SEM 0.52) mmol on the corresponding day on diet 2. Urinary Mg excretion as a percentage of estimated dietary intake was about double on the balanced mixed diet (37%) than on the Mg-rich vegetarian diet (24%). As both diets contained equal amounts of most nutrients, these results indicate a lower excretion rate of Mg from the vegetarian diet than from the mixed diet.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of dietary factors on the risk of urinary stone formation.

The action of various beverages and foods on the composition of the urine in the circadian rhythm and in the 24-hour urine has been investigated under standardized conditions. Orange juice leads to a significant increase of urinary pH and citric acid excretion. Black tea leads to a raised excretion of oxalic acid by only 7.9%. In the short term, beer increases diuresis, but afterwards leads to a compensatory antidiuresis with increased risk of stone formation. Depending on their composition, mineral waters have very different effects on the urinary constituents. Milk as well as cocoa beverage significantly increase calcium excretion; moreover, cocoa causes an increase in the oxalic acid excretion. The leafy vegetable foods containing oxalate, e.g., spinach and rhubarb, lead to peaks of oxalate excretion of 300-400% in the circadian excretion curve. Cheese leads to a significant rise of calcium excretion with acidification of the urine and lowering of citrate excretion. Calcium excretion is increased by 30% by sodium chloride. Foods containing purine result in an increased uric acid excretion over several days. Depending on their phytic acid content, brans bind calcium, but lead to an increased oxalic acid excretion. Analysis of the urine indicates that average diet in Germany entails a high risk of urinary stone formation. As a result of the change to a balanced mixed or vegetarian diet, according to the requirements, significant alterations in urinary pH, calcium, magnesium, uric acid, citric acid, cystine, and glycosaminoglycan excretion are measured, resulting in a drastic reduction in the risk of urinary stone formation.

[The effect of different food forms on the urine composition and the risk of calcium oxalate stone formation]. / Einfluss verschiedener Kostformen auf die Harnzusammensetzung und das Kalziumoxalat-Steinbildungsrisiko.

The aim of this 17-day study was to examine the influence of four different diets on urine composition and the risk of calcium oxalate stone formation in 10 healthy male subjects. In the course of phase 0, the subjects were on their individual diet for 2 days. In the following phases I, II, and III the subjects received three different standard diets for a duration of 5 days each. Whereas DIET 1 (normal mixed diet) corresponded to the dietary habits of men aged 19 to 35 years, DIET 2 (balanced mixed diet) and DIET 3 (ovo-lacto-vegetarian diet) were calculated according to the dietary recommendations of the German Society of Nutrition (DGE) for the same age-group. The risk of calcium oxalate stone formation, calculated by the computer program EQUIL of FINLAYSON, was highest on the self-selected diet and on DIET 1, but declined significantly on the intake of DIET 2 by 50% on average compared to DIET 1 and by 61% compared to phase 0. On DIET 3 no further significant decline in the risk of calcium oxalate stone formation was observed. Therefore, it can be concluded that the change of usual dietary habits into a balanced mixed diet significantly reduces the risk of calcium oxalate stone formation. With a vegetarian diet a comparable decline in urine supersaturation of calcium oxalate can be achieved with respect to a mixed diet according to requirements. Since urinary oxalic acid excretion increased significantly, a vegetarian diet is not recommend for calcium oxalate stone patients with absorptive hyperoxaluria.