High Rates of Thromboembolic Events in Patients with Germ Cell Cancer Undergoing Cisplatin-Based Polychemotherapy.

BACKGROUND: We examined whether or not extended prophylaxis with low molecular weight heparin (LMWH) would significantly reduce thromboembolic event (TEE) rates in germ cell cancer patients undergoing cisplatin-based chemotherapy. PATIENTS AND METHODS: LMWH prophylaxis was given from the first day of chemotherapy until 21 days after completing the last chemotherapy cycle to 45 out of 93 (48.4%) patients (extended), and to 48 out of 93 (51.6%) patients during their hospitalization only (limited) between January 2008 and December 2013. Patients were analyzed retrospectively for TEEs such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) or peripheral arterial thrombosis. RESULTS: A total of 22/93 (23.7%) patients experienced 30 TEE during chemotherapy: 12 out of 30 (40%) deep vein thrombosis, 4 out of 30 (13.3%) MI, 10 out of 30 (33.3%) PE and 4 out of 30 peripheral arterial thrombosis (13.3%). TEE rates in both groups did not differ significantly (extended: 26.7 vs. limited: 20.8%). CONCLUSIONS: The introduction of extended LMWH prophylaxis did not significantly reduce TEE rates in our patient cohort.

Salvage lymph node dissection with adjuvant radiotherapy for nodal recurrence of prostate cancer.

PURPOSE: We evaluated the impact of salvage lymph node dissection with adjuvant radiotherapy in patients with nodal recurrence of prostate cancer. By default, nodal recurrence of prostate cancer is treated with palliative antihormonal therapy, which causes serious side effects and invariably leads to the development of hormone refractory disease. MATERIALS AND METHODS: A total of 47 patients with nodal recurrence of prostate cancer based on evidence of (11)C-choline/(18)F-choline ((18)F-fluorethylcholine) positron emission tomography-computerized tomography underwent primary (2 of 52), secondary (45 of 52), tertiary (4 of 52) and quaternary (1 of 52) salvage lymph node dissection with histological confirmation. Of 52 salvage lymph node dissections 27 were followed by radiotherapy. Biochemical response was defined as a prostate specific antigen less than 0.2 ng/ml after salvage therapy. The Kaplan-Meier method, binary logistic regression and Cox regression were used to analyze survival as well as predictors of biochemical response and clinical progression. RESULTS: Mean prostate specific antigen at salvage lymph node dissection was 11.1 ng/ml. A mean of 23.3 lymph nodes were removed per salvage lymph node dissection. Median followup was 35.5 months. Of 52 salvage lymph node dissections 24 resulted in complete biochemical response followed by 1-year biochemical recurrence-free survival of 71.8%. Gleason 6 or less (OR 7.58, p = 0.026), Gleason 7a/b (OR 5.91, p = 0.042) and N0 status at primary therapy (OR 8.01, p = 0.011) were identified as independent predictors of biochemical response. Gleason 8-10 (HR 3.5, p = 0.039) as a preoperative variable, retroperitoneal positive lymph nodes (HR 3.76, p = 0.021) and incomplete biochemical response (HR 4.0, p = 0.031) were identified as postoperative predictors of clinical progression. Clinical progression-free survival was 25.6% and cancer specific survival was 77.7% at 5 years. CONCLUSIONS: Based on (11)C/(18)F-choline positron emission tomography-computerized tomography as a diagnostic tool, salvage lymph node dissection is feasible for the treatment of nodal recurrence of prostate cancer. Most patients experience biochemical recurrence after salvage lymph node dissection. However, a specific population has a lasting complete prostate specific antigen response.

Growth kinetics in von Hippel-Lindau-associated renal cell carcinoma.

OBJECTIVE: To evaluate the growth kinetics of renal cell carcinoma (RCC) in von Hippel-Lindau (VHL) disease in a large trial by CT/MRI scan. VHL disease is a multisystemic disorder predisposing to renal cysts and cancer. There is a general assumption that VHL-associated RCC presents slower growth rates than sporadic RCC. PATIENTS AND METHODS: We describe growth kinetics of 96 renal tumours in 64 VHL patients with analysed germline mutation (54/64 treated, 10/64 active surveillance) over a mean follow-up of 54.9 months. We calculated tumour volume, growth rate, multiplication of tumour volume per year and overall, as well as tumour volume doubling time. RESULTS: The mean growth rate of 96 tumours was 4.4 mm/year (SD 3.2, median 4.1 mm/year), mean volume doubling time was 25.7 months (SD 20.2, median 22.2 months). We saw a median 1.4-fold increase in tumour volume per year. At treatment time point, VHL kidneys comprised 39% tumour and 15.7% cyst volume fraction. We saw no correlation between tumour size and growth parameters. CONCLUSION: VHL-associated RCC show large variances in tumour growth behaviour. Compared to the literature, in our study the growth rates (mm/year) of RCC in VHL disease did not differ from those of sporadic RCC. Fast tumour growth increases the risk for metastases.

Comprehensive analysis of complications after transperineal prostate biopsy without antibiotic prophylaxis: results of a multicenter trial with 30 days' follow-up.

BACKGROUND: To investigate infectious and non-infectious complications after transperineal prostate biopsy (TPB) without antibiotic prophylaxis in a multicenter cohort. Secondly, to identify whether increasing the number of cores was predictive for the occurrence of complications. Thirdly, to examine the relation between TPB and erectile dysfunction. METHODS: We analyzed a retrospective multicenter cohort of 550 patients from three different urological centers undergoing TPB without antibiotic prophylaxis. The median number of cores was 26. Demographic and clinical data were extracted by reviewing patients' electronic medical records and follow-up data such as postoperative complications obtained by structured phone interviews. To investigate the influence of the number of cores taken on the occurrence of complications, we performed univariate and multivariate mixed effects logistic regression models. RESULTS: There was no case of sepsis reported. Overall, 6.0% of patients (33/550) presented with any complication besides mild macrohematuria. In all, 46/47 (98%) complications were ≤Grade 2 according to Clavien-Dindo. In multivariate regression analyses, an increased number of cores was associated with overall complications (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.02-1.14, P = 0.01) and specifically bleeding complications (OR 1.28, 95% CI 1.11-1.50, P = 0.01) but not with infectious complications (OR 1.03, 95% CI 0.97-1.10, P = 0.67). A total of 14.4% of patients referred impairment of erectile function after TPB. Of note, 98% of these men were diagnosed with prostate cancer. CONCLUSIONS: This is the first multicenter trial to investigate complications after TPB without antibiotic prophylaxis. In our study, we found no case of sepsis. This underlines the safety advantage of TPB even without antibiotic prophylaxis and supports the ongoing initiative to abandon TRB of the prostate. A higher number of cores were associated with an increase in overall complications specifically bleeding complications, but not with infectious complications. Post-biopsy erectile dysfunction was mainly present in patients diagnosed with PCa.

[Treatment mapping of lower urinary tract symptoms due to benign prostatic hyperplasia-an analysis of the Governing Body of German Prostate Centers]. / Versorgungsabbild des benignen Prostatasyndroms ­ eine Analyse des Dachverbandes der Prostatazentren Deutschlands (DVPZ) e. V.

BACKGROUND: Due to the high incidence and demographic development, there is an urgent need for healthcare research data on lower urinary tract symptoms due to benign prostatic hyperplasia (LTUS/BPH). Since 2005 the Governing Body of German Prostate Centers (DVPZ) has been collecting data from 22 prostate centers in order to determine the quality and type of cross-sectoral care in particular for LUTS/BPH patients. OBJECTIVES: Presentation of the DVPZ database in general, as well as an investigation of treatment patterns for medical and instrumental therapies. MATERIALS AND METHODS: The analysis is based on UroCloud data sets from 30 November 2017. In the UroCloud data on diagnostics, therapy and course of disease are recorded in a web-based manner. RESULTS: A total of 29,555 therapies were documented for 18,299 patients (1.6/patient), divided into 48.5% instrumental, 29.2% medical treatment, and 18.0% "wait and see" (in 4.3% no assignment was possible). Patients treated with an instrumental therapy were oldest (median: 72 years, interquartile range: 66-77), had the largest prostate volumes (50 ml, 35-75 ml), and were mostly bothered by symptoms (International Prostate Symptom Score = 19/4). The majority of patients under medical treatment received alphablockers (56%); phytotherapeutics were used least frequently (3%). Instrumental therapies are dominated by transurethral resection (TUR) of the prostate (60.0%), open prostatectomy (9.4%) and laser therapy (5.0%), with laser therapy having the shortest hospital stay (5 days) and the lowest transfusion and re-intervention rates (1.0% and 4.6%, respectively). CONCLUSIONS: The DVPZ certificate covers the complete spectrum of cross-sectoral care for LUTS/BPH patients and documents the use of the various therapies as well as their application and effectiveness in the daily routine setting.

Standard of Care Versus Metastases-directed Therapy for PET-detected Nodal Oligorecurrent Prostate Cancer Following Multimodality Treatment: A Multi-institutional Case-control Study.

BACKGROUND: Most prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes. OBJECTIVE: To perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT). DESIGN, SETTING, AND PARTICIPANTS: PCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis. INTERVENTION: The SOC cohort (n=1816) received immediate or delayed androgen deprivation therapy administered at PSA progression. The MDT cohort (n=263) received either salvage lymph node dissection (n=166) or stereotactic body radiotherapy (n=97) at PSA progression to a positron emission tomography-detected nodal recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint, cancer-specific survival (CSS), was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. RESULTS AND LIMITATIONS: At a median follow-up of 70 (interquartile range: 48-98) mo, MDT was associated with an improved CSS on univariate (p=0.029) and multivariate analysis (hazard ratio: 0.33, 95% confidence interval [CI]: 0.17-0.64) adjusted for the year of radical prostatectomy (RP), age at RP, PSA at RP, time from RP to PSA progression, Gleason score, surgical margin status, pT- and pN-stage. In total, 659 men were matched (3:1 ratio). The 5-yr CSS was 98.6% (95% CI: 94.3-99.6) and 95.7% (95% CI: 93.2-97.3) for MDT and SOC, respectively (p=0.005, log-rank). The main limitations of our study are its retrospective design and lack of standardization of systemic treatment in the SOC cohort. CONCLUSIONS: MDT for nodal oligorecurrent PCa improves CSS as compared with SOC. These retrospective data from a multi-institutional pooled analysis should be considered as hypothesis-generating and inform future randomized trials in this setting. PATIENT SUMMARY: Prostate cancer patients experiencing a lymph node recurrence might benefit from local treatments directed at these lymph nodes.

[Von Hippel-Lindau disease. Interdisciplinary patient care]. / Von-Hippel-Lindau-Erkrankung. Interdisziplinäre Patientenversorgung.

Von Hippel-Lindau disease is an important hereditary tumor syndrome with a clear option for effective treatment if diagnosed in time. Interdisciplinary cooperation is the key to successful management. Major components of the disease are retinal capillary hemangioblastomas, hemangioblastomas of cerebellum, brain stem and spine, renal clear cell carcinomas, pheochromocytomas, multiple pancreatic cysts and islet cell carcinomas, tumors of the endolymphatic sac of the inner ear, and cystadenomas of the epididymis and broad ligament. A well structured screening program should be performed at yearly intervals.

[Treatment mapping of prostate cancer in DVPZ prostate centers in Germany]. / Versorgungsabbild zum Prostatakarzinom in DVPZ-Prostatazentren in Deutschland.

BACKGROUND: In prostate centers of the Governing Body of German Prostate Centers (DVPZ, Dachverband der Prostatazentren Deutschlands e.V.) treatment data from 3 university clinics, 21 treatment clinics, 3 private clinics and 330 general practitioners incorporated under 22 certificates are collated, in order to document the quality and type of cross-sectoral and interdisciplinary treatment, in particular of prostate cancer (PCA) patients. METHODS: This analysis is based on the DVPZ UroCloud data sets from 20 July 2015. The UroCloud reflects the web-based chronological disease development and quality parameters. For the descriptive analysis of particular key figures, available complete data sets were selected. RESULTS: Of the centers 22 held a valid certificate and fulfilled all required case numbers and structural prerequisites at the primary certification or recertification. In three cases a reauditing led to requirements before certification. Since 2005 a total of 9650 PCA patients have been pseudonymized and followed up (41,247 follow-up forms, 4.3 forms per patient). In 2014 the median number of newly documented PCA patients was 61 per center (minimum 7 and maximum 295). Radical prostatectomy (RP) dominated with 4491 (56 %) cases followed by primary hormonal therapy (1210 cases, 15 %), irradiation (809, 10 %) and non-interventional therapy, such as active surveillance (AS) or watchful waiting (WW) in 760 cases (10 %). A prostate-specific antigen (PSA) reduction was documented in 50 % of the patients with a preoperative PSA value > 20, in 60 % of pT4 tumors and in 50 % of patients with a tumor Gleason score of 9-10. A positive incision margin (R+) was found in in 15 % of pT2 stages, 41 % of pT3 stages and 85 % of pT4 stages. A secondary intervention was documented in 6.5 % of RP. CONCLUSION: The DVPZ certificate reflects the complete spectrum of treatment of PCA patients. The strength of the certificate lies in the documentation of patient development and a simultaneous collation of quality parameters.

Beta-adrenergic, angiotensin II, and bradykinin receptors enhance neurotransmission in human kidney.

The aim of this study was to investigate angiotensin II (Ang II) receptor-, bradykinin receptor-, and beta-adrenergic receptor-mediated modulation of norepinephrine release from human renal sympathetic nerves and to characterize the respective receptor subtypes involved. Human cortical kidney slices were incubated with [3H]norepinephrine, placed in superfusion chambers between two platinum electrodes, and superfused with Krebs-Henseleit solution. The sympathetic nerves were stimulated electrically at 2.5 Hz for 1 minute, and the stimulation-induced outflow of radioactivity was taken as an index of endogenous norepinephrine release. Ang II and its precursor Ang I (both 0.01 to 1 mumol/L) enhanced stimulation-induced outflow of radioactivity in a concentration-dependent manner, with EC50 values of 0.03 and 0.05 mumol/L, respectively. The enhancement by Ang I but not that by Ang II was inhibited by the angiotensin-converting enzyme inhibitor captopril (3 mumol/L). The concentration-response curves of Ang I and Ang II were shifted to the right by EXP 3174 (0.01 mumol), the in vitro active form of the Ang II type 1 receptor antagonist losartan, with affinity estimates of 8.72 and 9.30, respectively. A higher concentration of EXP 3174 (0.1 mumol/L) abolished the facilitatory effects of Ang I and Ang II. The Ang II type 2 receptor antagonist PD 123319 (10 mumol/L) did not alter the facilitation by Ang II. In the absence of other drugs, bradykinin (0.01 to 1 mumol/L) failed to modulate stimulation-induced outflow of radioactivity but in the presence of captopril (3 mumol/L) enhanced it in a concentration-dependent manner, with an EC50 of 0.1 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue disposition and plasma concentrations of idarubicin after intravesical therapy in patients with bladder tumors.

We studied single doses of intravesical idarubicin (IDA) given as 1-h instillations to 33 patients with bladder tumors. The dose was escalated from 5 to 30 mg and the concentration, from 0.25 to 1.5 mg/ml for evaluation of the importance of both the total amount of drug and the drug concentration on the levels of IDA found in different tissues (tumor, mucosa and muscle). Additionally, plasma uptake over 24 h was studied. The results demonstrated that (1) the levels of IDA in extracts of bladder tumors were significantly higher than those in normal bladder tissue, (2) the incorporation of IDA into tumors depended on the total amount of drug instilled and on the concentration of drug in the instillation fluid, (3) cytotoxic concentrations of IDA were noted in all tumors when the total amount of drug instilled was greater than 15 mg and the drug concentration in the instillation fluid was greater than 0.33 mg/ml, and (4) plasma levels of IDA were negligible.

Correlation of clinical and immunological parameters of metastatic renal cell carcinoma patients undergoing therapy with interleukin 2, interferon-alpha and retinoic acid.

IFN-gamma production in whole blood cell cultures (WBCC), and TNF-receptor p75 (TNF-R-75) plasma levels were measured as two independent immunological parameters in a group of 67 untreated renal cell carcinoma (RCC) patients at different clinical stages, and 40 age matched healthy controls. In the blood cell cultures of the tumor patients the levels of IFN-gamma were significantly lower compared to the controls and the values decreased with increasing tumor mass. In contrast, TNF-R-75 plasma levels were significantly higher in the tumor patients and increased with tumor stage. Additionally serial assessments of these parameters were studied in another group of 15 patients with advanced RCC during treatment with IL-2, IFN-alpha and retinoic acid according to three different protocols in order to search for any correlation between the biological marker values and the clinical response to treatment. During each 5 day cycle of high dose IL-2/IFN-alpha combination therapy (protocol 1) IFN-gamma-levels in the WBCC were markedly decreased, whereas the plasma levels of TNF-R-75 were increased. During low dose, long-term continuous IFN-alpha/IL-2 administration (protocol 2) in two patients a clear increase of the ex vivo leukocyte IFN-gamma production was seen for the first 5 and 6 months of treatment, respectively, which could be correlated to stable disease for this time. When progression was diagnosed, IFN-gamma levels in the WBCC decreased. In the WBCC of the other four patients with progressive IFN-gamma levels were rather low throughout (< 10 ng/ml) and no clear changes were measured. During low does IFN-alpha and 13-cis-retinoic acid therapy in repetitive weekly cycles (protocol 3) two patients had stable disease for 6 and 14 months respectively. In the WBCC cultures of these patients IFN-gamma production was higher during stable than during progressive disease. The other two patients with tumor progression had a very low leukocyte IFN-gamma production and high plasma levels of TNF-R-75. It is concluded that IFN-gamma levels in WBCC and TNF-R-75 plasma levels may be useful parameters for the immunological monitoring of therapies with biological response modifiers. Low IFN-gamma values and high TNF-R-75 levels may be predictive of tumor progression and bad prognosis.

Digitization and postprocessing of plain-film radiographs for assessment of stone fragmentation after extracorporeal shockwave lithotripsy.

In 50 patients treated for urolithiasis by extracorporeal shockwave lithotripsy (ESWL++), the radiographs taken before and 1 day afterward were initially assessed by conventional radiography and subsequently after standardized digitization and postprocessing. Clinical outcome and passage of stone fragments were reevaluated 3 weeks after ESWL. Using specially developed software routines, new disintegration parameters could be obtained by detecting the number of relevant minima in light-intensity distribution along the length axis of the concrement in digitized images. Comparing the digitized images before with those after ESWL, the concremental surface and axial length in digitized images on average showed no statistically significant difference. However, the number of visually and automatically detected light-intensity minima of the concrement region in digitized images obtained 1 day after ESWL was significantly higher than prior to ESWL and correlated significantly with the number of fissure lines in the conventional images. These new features in digitized images showed a high sensitivity in predicting later passage of stone fragments. Moreover, in six of the seven patients without detectable fissure lines in the early conventional radiographs but obvious signs of concretemental disintegration 3 weeks after ESWL, there was an increase in the number of light-intensity minima in the digitized images 1 day after ESWL. Our findings indicate that this method of digitization and post-processing of radiographs may improve the assessment of ESWL effectiveness by improving standardization in the analysis of all surveyed parameters and by offering new relevant disintegration measures.

Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in urological malignancies.

Several studies suggest that cellular adhesion molecules (CAM) play a role in cancer progression and metastasis. To evaluate the role of these molecules as possible tumor markers in patients with urological malignancies, we examined the serum levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular cellcular adhesion molecule-1 (VCAM-1) and E-selectin in patients with renal cell-, bladder-, prostate- and testicular cancer. Serum levels of 237 patients with urological cancers, renal cell carcinoma (n = 47), bladder cancer (n = 81), prostate cancer (n = 87) and testicular cancer (n = 22) and a group of 41 patients with benign prostate hyperplasia (BPH) as well as a 42 healthy control persons were examined for CAMs by specific ELISA tests. Serum CAM concentrations of all tumor patients were compared with controls and within the group according to T stage, N stage, tumor grade and extent of distant metastasis. Our results demonstrate that ICAM-1 and VCAM-1 serum levels are not stage dependently elevated; in contrary, they demonstrate a wide range and are highly variable throughout the different cancer types. In renal cell cancer and in bladder cancer, there is a significant difference for ICAM-1 between controls and T3 and T4 and metastatic cancers. A similar difference was found for VCAM-1, however not for E-selectin in any tumor group. Testicular cancer and prostate cancer did not demonstrate any difference in CAM serum levels between patients with tumors and controls. In metastatic renal cell-, bladder- and prostate cancer, the serum levels of ICAM-1 and VCAM-1 showed a tendency to correlate with the extent of metastatis although no statistical difference between patients with a single metastatic lesion and patients with multiple lesions could be demonstrated. The results of this study implicate a rather limited role of cellular adhesion molecules. Despite of significant ICAM-1 or VCAM-1 serum levels in some locally advanced tumors or metastatic disease, this observation does not provide enough relevant clinical information for use as tumor markers.

Nephron sparing surgery in von Hippel-Lindau associated renal cell carcinoma; clinicopathological long-term follow-up.

We evaluated the clinicopathological outcome of von Hippel-Lindau (VHL)-patients who had mainly undergone nephron sparing surgery (NSS) for renal cell carcinoma (RCC) when the tumour diameter has reached 4.0 cm. Multiple, bilateral RCC with high recurrence rates and subsequent repeated interventions, followed by increasing risk for end-stage renal failure and metastases is characteristic for VHL. NSS is widely used for VHL-associated RCC at 3.0 cm cut-off. 54 VHL patients underwent NSS, nephrectomy or thermal ablation for RCC. We analysed time to second treatment, overall and cancer specific survival, intra- and post-operative data as well as tumour characteristics. We also examined the effects of delaying removal of RCC to 4.0 cm cut-off. Median follow-up was 67 months. 54 patients underwent 97 kidney treatments. 96 % of first and 67 % of second interventions comprised of NSS. 0 % metastases were observed in the group with largest tumour size ≤4 cm. The probability for second surgery was 21 %, at 5 years and 42 % at 10 years. Median time to second NSS was 149.6 months. The overall and cancer specific survival rate was 96.5 and 100 % at 5-year follow-up, and 82.5 and 90.5 % respectively at 10-year follow-up. Median delay to second NSS at 4.0 cm cut-off versus 3.0 cm was 27.8 months. NSS was both successfully used in first and second surgery and to some extent even in third surgery. By following a strict surveillance protocol it is possible to support a 4.0 cm-threshold strategy for NSS, based on the assumption that delaying time to second NSS prevents patients from premature renal failure.

A bispecific diabody directed against prostate-specific membrane antigen and CD3 induces T-cell mediated lysis of prostate cancer cells.

BACKGROUND: Although cancer of the prostate is one of the most commonly diagnosed cancers in men, no curative treatment currently exists after its progression beyond resectable boundaries. Therefore, new agents for targeted treatment strategies are needed. Cross-linking of tumor antigens with T-cell associated antigens by bispecific monoclonal antibodies have been shown to increase antigen-specific cytotoxicity in T-cells. Since the prostate-specific membrane antigen (PSMA) represents an excellent tumor target, immunotherapy with bispecific diabodies could be a promising novel treatment option for prostate cancer. METHODS: A heterodimeric diabody specific for human PSMA and the T-cell antigen CD3 was constructed from the DNA of anti-CD3 and anti-PSMA single chain Fv fragments (scFv). It was expressed in E. coli using a vector containing a bicistronic operon for co-secretion of the hybrid scFv V(H)CD3-V(L)PSMA and V(H)PSMA-V(L)CD3. The resulting PSMAxCD3 diabody was purified from the periplasmic extract by immobilized metal affinity chromatography (IMAC). The binding properties were tested on PSMA-expressing prostate cancer cells and PSMA-negative cell lines as well as on Jurkat cells by flow cytometry. For in vitro functional analysis, a cell viability test (WST) was used. For in vivo evaluation the diabody was applied together with human peripheral blood lymphocytes (PBL) in a C4-2 xenograft-SCID mouse model. RESULTS: By Blue Native gel electrophoresis, it could be shown that the PSMAxCD3 diabody is mainly a tetramer. Specific binding both to CD3-expressing Jurkat cells and PSMA-expressing C4-2 cells was shown by flow cytometry. In vitro, the diabody proved to be a potent agent for retargeting PBL to lyze C4-2 prostate cancer cells. Treatment of SCID mice inoculated with C4-2 tumor xenografts with the diabody and PBL efficiently inhibited tumor growth. CONCLUSIONS: The PSMAxCD3 diabody bears the potential for facilitating immunotherapy of prostate cancer and for the elimination of minimal residual disease.

[Benign prostatic hyperplasia--choice of therapy in the elderly]. / Benigne Prostatahyperplasie--Therapiewahl im Alter.

The incidence of benign prostatic hyperplasia of up to 80% in 80-year-old men raises question as to possible therapeutic consequences. For decades, the standard treatment has consisted in transurethral resection of the prostate (TUR-P) which results in subjective and objective improvement in up to 95% of the cases and has low morbidity and negligible mortality. With a view to establishing a minimally invasive form of treatment, the search for alternative therapies makes good sense. To date, however, various medical therapeutic approaches (phytotherapy, alpha-blockers, antiandrogens, 5-alpha-reductase inhibitors) and/or interventional measures (thermotherapy, stents, balloon dilatation) have failed to match the therapeutic efficacy of TUR. However, in individuals at a high risk of surgery, they represent practicable alternatives.

[Limits of surgical therapy of prostate cancer in the aged?]. / Grenzen der operativen Therapie des Prostatakarzinoms im Alter?

The incidence of carcinoma of the prostate is increasing throughout the entire western world. The general rise in life expectancy is associated with the fact that many of these carcinomas of old age are now becoming clinically relevant. For curative treatment of prostate carcinoma, three procedures are available (radical prostatectomy, brachytherapy, radiotherapy). In terms of local freedom from tumor and long-term survival, radical prostatectomy is superior to the other modalities. Since improvements in our knowledge of the relevant anatomy have considerably reduced surgical morbidity and mortality, the procedure represents standard treatment in patients with a statistical life expectancy of at least 10 years and locally limited carcinoma of the prostate.

Kidney-preserving tumour resection in renal cell carcinoma with photodynamic detection by 5-aminolaevulinic acid: preclinical and preliminary clinical results.

OBJECTIVE: To identify the outer border of a renal cell carcinoma (RCC) during a kidney-preserving tumour resection by photodynamically detecting RCC after the exogenous administration of 5-aminolaevulinic acid (ALA) in an animal model and in humans. PATIENTS, MATERIALS AND METHODS: Human RCC was xenotransplanted subcutaneously and orthotopically into the kidneys of nude mice. ALA was then administered orally or intravenously (100-400 mg/kg body weight). The tumours were removed and examined macroscopically and microscopically for fluorescence, and the concentrations of protoporphyrin IX (PPIX) evaluated in the subcutaneous tumours. In a pilot study, nine patients with RCC of <4 cm diameter underwent partial nephrectomy; 20 mg ALA/kg body weight was given orally 4 h before surgery. During the operation, the macroscopic fluorescence of the tumours was evaluated and any side-effects recorded. RESULTS: In the mouse model, the RCC fluoresced in all tumours, both macro- and microscopically, reaching a maximum 1.5 h after intravenous and 4 h after oral administration. The tissue concentrations of PPIX in the subcutaneous tumours were also maximal 4 h after oral administration. In the patients undergoing surgery, the RCC also fluoresced clearly and was sufficiently intense to identify the outer margins of the tumours for kidney-preserving tumour resection. There were no side-effects of the ALA with the dosages and methods of administration used. CONCLUSION: The photodynamic detection of RCC with ALA facilitates the identification of tumour margins in man and in the mouse model, producing no undesirable side-effects. It may be helpful in determining the boundaries of the resected tissue when carrying out conservative kidney-preserving surgery.

Intravesical idarubicin--a phase-I study.

In the scope of a pharmacokinetic and dose-finding study 33 patients received instillations of idarubicin in 11 different doses 1 h before scheduled transurethral resection of bladder cancer. The dose was increased continuously from 5 to 30 mg and the concentration from 0.25-1.5 mg/ml. Idarubicin uptake into tissue was measured along with the serum level. The results showed a clear correlation of the tissue levels with dose and concentration. A significantly higher concentration of idarubicin was measured in the tumor in comparison with the mucosa. Absorption into the muscle was minimal and serum levels were low. Systemic toxicity was not observed, but there were signs of local toxicity in 50% of the subjects. Cytotoxic concentrations in the mucosa were reached at doses of over 15 mg and concentrations of over 0.5 mg/ml. A phase-II study is in preparation.