[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.

The role of urinary cytology for detection of bladder cancer.

PURPOSE: The aim of the present study was to test the value of urinary cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: One thousand three hundred and eighty voided urine and bladder wash specimens of 495 patients were evaluated by urinary cytology. All patients then underwent transurethral resection of suspicious bladder areas if cystoscopy and/or preceding biopsy were positive. Statistical differences were analysed using the two-sided Fisher's exact test and Cochran's test (p<0.05). RESULTS: In 495 patients including 142 patients with bladder cancer urinary cytology revealed a sensitivity of 38.0% and a specificity of 98.3% with a positive and negative predictive value of 90.6 and 78.6, respectively. Sensitivity increased significantly with malignancy grade (p<0.05). In high grade tumours sensitivity improved from initial 52.2% up to 78.3% after the third sample. In sensitivity and specificity of voided urine and barbotage washing samples no significant difference was detected. CONCLUSIONS: Urinary cytology has its place as an additive diagnostic tool to cystoscopy. None of the currently available urinary markers can replace cystoscopy but are helpful for specific diagnostic problems.

[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.

Studies on the differentiation pathway and growth characteristics of epithelial culture cells of the human prostate.

We established explant primary cultures in order to study the growth and hormone responsiveness, and the differentiation process of prostatic epithelial cells. Cell outgrowth was achieved from explant tissue by using a new DU145-cell-conditioned medium and special plastic coverslips. To define the present model, proliferation assays were tested by [3H]thymidine assay and planimetric analysis. Cells were analyzed using immunocytochemistry, light, phase contrast and electron microscopy, polymerase chain reaction, telomerase ELISA and immunoassay (PSA). Morphology and electron microscopy revealed typical epithelial differentiation. Immunocytochemistry showed the content of basal and secretory epithelial cells, endocrine paracrine cells and a high level of proliferation. With increasing culture time, mature epithelial differentiation (PSA) increases and the initial increase of alpha-smooth muscle actin (alpha-SMA) decreases again. After further passaging, alpha-SMA expression is no longer detected and PSA expression decreases. Furthermore, epithelial cells showed both androgen responsiveness and androgen receptor expression. These findings show the presence of epithelial cells in a process of differentiation with endocrine paracrine cells and a high level of proliferation. This model may maintain the cellular and functional properties more closely related to the human prostate and may provide a valuable tool for studying stem cells and differentiation characteristics.

[Improved tumor stent for internal palliative urinary diversion]. / Neu entwickelter Tumorstent zur internisierten palliativen Harnableitung.

The disadvantages of high flexible endoureteral stents (DJ) in case of tumorinduced extrinsic ureteral compression are due to an insufficient vertical stability of the used stents leading to stent-compression and consecutive hydro- or pyonephrosis. The new developed tumor-stent used in case of tumor-induced ureteral compression is available from 6 to 8 French in diameter and 24 to 32 cm in length. The corpus consists of a combination of high-stability plastics but is of sufficient elasticity in length. Both ends consist of extremely elastic J-parts guaranteeing an exact fixation. As against common DJ's with the same outside-diameter the new stent has a comparable interior diameter and compared to used "old" tumor stents promises a higher interior flow in case of extrinsic diseases. The application can be undertaken in well-known technique, needs no special instrumentation and no learning-curve. To date 52 stents at our urologic departments were placed without any problems, the latest remaining for 15 months. Tumor-induced compression or a higher rate of encrustation could not be seen. All patients tolerated these stents well. In our opinion the new stabilized endoureteral stent can be seen as a better solution instead of percutaneous nephrostomy or frequent stent changing in patients with tumor induced extrinsic ureteral compression.

[Primary sarcomatoid carcinoma of the ureter]. / Primäres sarkomatoides Karzinom des Ureters.

INTRODUCTION: We present a case of unusually rapid tumor progression in a patient with primary sarcomatoid carcinoma of the ureter. CASE REPORT: An 82-year-old female patient underwent total nephroureterectomy for a ureteral tumor that turned out to be a primary sarcomatoid carcinoma of the ureter. After a normal postoperative course, the patient developed a metastatic symptomatic that seemed to have appeared "like an explosion" on the 33rd p. o. day. She died shortly thereafter. CONCLUSION: This is the second case of primary sarcomatoid carcinoma of the ureter published in the literature, a rare and aggressive variant of urothelial carcinoma with a highly malignant potential. As no effective adjuvant treatment has been reported as yet, we recommend mandatory radical excision of the sarcomatoid tumor and early postoperative radiation therapy to increase survival.

[Chronic prostatitis. Chronic pelvic pain syndrome]. / Chronische abakterielle Prostatitis. Ein chronisches Beckenbodenschmerzsyndrom in der Urologie.

The symptom complex called prostatitis represents a multifactorial problem of unclear etiology. Standardized diagnostic and therapeutic approaches do not exist. Controlled studies which fulfil evidence-based medical criteria are missing. A review of the currently available literature leads to the conclusion that a multimodal therapy concept should be developed and examined.

DNA aneuploidy in G1-urothelial carcinomas of the urinary bladder.

Thirty G1-urothelial carcinomas of the bladder were investigated using DNA cytophotometry. Specimens obtained by tumour resection and quadrantic biopsy were first fixed in formalin and then embedded in paraffin. The cells were then separated using the method developed by Hedley. The DNA content was established after Feulgen staining using a TV-based image analysis system. DNA aneuploidy, a marker for neoplasia, was investigated using the so-called stemline interpretation developed by Böcking. This method compares the DNA content of the G0/1 tumour cells in the cell population to be analysed with the reference cell population, using the Kolmogoroff-Smirnow test (p < 0.001). On this basis, 23 tumours (76.6%) were DNA aneuploid, whereas if DNA aneuploidy is defined (as conventionally) as a DNA content of > 2.2c, only 17 tumours (56.6%) were found to be DNA aneuploid. The mean stemline value was 2.4c (range 1.85-3.96). By using a more precise TV-based image analysis system and this new DNA stemline interpretation, the rate of detection of DNA aneuploidy was improved by 20%. The diagnosis of G1-urothelial carcinomas by DNA cytophotometry is at least 25% more sensitive than that using conventional cytology (20-50%). We suggest that modified DNA cytophotometry could be a useful, additional diagnostic tool in examining doubtful urinary samples.

Second in situ extracorporeal shock wave lithotripsy in not disintegrated ureteral stones is preferred to retrograde manipulation.

In this study we tried to determine the optimal treatment of upper ureteral stones which are not disintegrated by the first extracorporeal shock wave lithotripsy (ESWL) and to analyze the cost-benefit ratio of retrograde manipulation into the renal pelvis. 180 patients with an upper ureteral stone were treated by ESWL in situ. 40 patients needed a retreatment and were randomized for retrograde manipulation before ESWL or ESWL in situ without a prior manipulation. In both the in situ group and in the push-and-smash group, the stone-free rate was 75%. In stones < 8 mm, the disintegration rate was higher after retrograde manipulation into the renal pelvis and inserting a DJ catheter. In conclusion, ESWL in situ is the optimal treatment for all patients with upper ureteral stones. We reserve retrograde manipulation before a second ESWL for stones < 8 mm. Routinely employed auxiliary procedures such as placement of a DJ catheter increase the costs significantly, without improving the results.

Use of Lewis X antigen and deoxyribonucleic acid image cytometry to increase sensitivity of urinary cytology in transitional cell carcinoma of the bladder.

PURPOSE: To improve sensitivity and specificity of urinary cytology for bladder cancer cell detection we used deoxyribonucleic acid (DNA) image cytometry and the monoclonal anti-Lewis X antibody P12. MATERIALS AND METHODS: Spontaneously voided urine and additional barbotage bladder washings of 25 patients with transitional cell carcinomas and 25 patients with benign diseases of the bladder were analyzed by conventional cytology, immunocytology and DNA image cytometry. The DNA content was determined in specimens stained with Feulgen according to the European Society for Analytical Cellular Pathology consensus report on standardization of DNA image cytometry. For the immunocytological examination we used the avidin-biotin-complex immunoperoxidase method with the monoclonal antibody P12 directed against the Lewis X determinant. RESULTS: The cytological examination revealed a sensitivity of 72% and a specificity of 100%. By using DNA image cytometry with Kolmogoroff-Smirnow test sensitivity increased up to 84% with a specificity of 100%. The immunocytological examination with Lewis X showed a sensitivity of 84% and a specificity of 80%. CONCLUSIONS: Combining cytology and DNA cytometry the overall sensitivity increased to 92% and with the additional application of immunocytology for Lewis X antigen sensitivity it increased to 96% but was accompanied by a decrease in specificity to 80%. DNA image cytometry and Lewis X antigen detection are not suitable for screening but suspicious urothelial cells in urinary cytology specimens can be evaluated specifically by DNA measurements. In the future it needs to be clarified whether DNA image cytometry in combination with Lewis X antigen detection can help to signal relapse and progression of transitional cell carcinoma of the bladder.

Diagnosis of bladder cancer with urinary cytology, immunocytology and DNA-image-cytometry.

DNA-image-cytometry and antibodies directed against the Lewis X- and the 486p 3/12 antigen were applied to improve diagnostic accuracy of urinary cytology for the detection of bladder cancer. Cytology, immunocytology and DNA-image-cytometry were performed in spontaneously voided urine samples and barbotage bladder washings from 71 patients. The DNA content was determined using the CM-1 Cytometer according to the recommendation of the ESCAP Consensus Report on Standardization of DNA-image-cytometry (1995). For immunocytological examination we used the monoclonal anti Lewis X antibody P-12 and antibody 486p 3/12. All patients underwent subsequent cystoscopy and for any suspicious lesion biopsy or transurethral resection was done. Histological findings revealed 31 patients with transitional cell carcinomas of different stages and grades of malignancy. 40 patients had various benign diseases of the urinary bladder. Cytology yielded a sensitivity of 68% and a specificity of 100%. DNA aneuploidy was detected in 81% of cancer patients with a specificity of 100%. By combination of these two methods the overall sensitivity increased to 87%. Immunocytology with Lewis X and 486p 3/12 antibodies showed reactivity in 84% and 87% in combination with a specificity of 80% and 70%, respectively. By combining urinary cytology, immunocytology and/or DNA-image-cytometry the overall sensitivity increased to 94% with no change in specificity. DNA-image-cytometry should be used to evaluate particularly urothelial cells suspicious for malignancy in urinary specimens. Because of low specificity the monoclonal antibodies against Lewis X- and 486p 3/12 antigens are not helpful in screening for bladder cancer. Nevertheless, their high sensitivity may justify their use in case DNA image cytometry is not available and in the follow up of patients with transitional cell carcinoma.

Regulation of keratinocyte growth factor receptor and androgen receptor in epithelial cells of the human prostate.

PURPOSE: Stromal-epithelial interactions of growth factors and the androgen receptor may have implications for the pathophysiology of benign and neoplastic transformation of the human adult prostate. We investigated a possible interaction of keratinocyte growth factor with its receptor as well as with the androgen receptor signaling pathway in human prostatic epithelial cells. MATERIALS AND METHODS: Human prostatic epithelial cells were obtained from explant primary culture, established in DU145 cell conditioned medium and maintained in keratinocyte serum-free medium with supplements. Epithelial cells were characterized by light and electron microscopy, and immunocytochemical study using epithelial and mesenchymal markers. Androgen receptor, keratinocyte growth factor receptor and keratinocyte growth factor messenger RNA expression was measured by polymerase chain reaction (PCR). The response to 0.01 to 10 nM. dihydrotestosterone, 10 microM. flutamide and 1 to 1,000 ng./ml. keratinocyte growth factor was tested by [3H] thymidine assay. The difference in keratinocyte growth factor receptor and androgen receptor gene expression after treatment with and without keratinocyte growth factor and flutamide were determined by quantitative multiplex PCR and quantitated using densitometry analysis. RESULTS: Immunocytochemical and electron microscopy characterization revealed typical epithelial differentiation. PCR showed keratinocyte growth factor receptor and androgen receptor expression in epithelial cultured cells but no keratinocyte growth factor expression. Epithelial cells showed a significant time and dose dependent stimulation of cell proliferation with keratinocyte growth factor and dihydrotestosterone (p <0.05). When combined with the anti-androgen flutamide the effect of 100 ng./ml. keratinocyte growth factor was significantly decreased (p <0.05). At 100 ng./ml. keratinocyte growth factor quantitative multiplex PCR revealed stimulated keratinocyte growth factor receptor and androgen receptor messenger RNA expression. CONCLUSIONS: These results show that keratinocyte growth factor up-regulates the keratinocyte growth factor and androgen receptors in the absence of androgen. Thus, the androgen signaling pathway may be activated by growth factors such as keratinocyte growth factor in an androgen deficient environment.

Diagnostic accuracy of DNA image cytometry and urinary cytology with cells from voided urine in the detection of bladder cancer.

OBJECTIVES: To assess the potential of DNA image cytometry in screening for bladder cancer, compare it with conventional urinary cytology, and evaluate its possible use in routine urinary evaluation. Urinary cytology is still the most common method for detection of bladder cancer in routine clinical use. The considerable shortcomings of urinary cytology include its low sensitivity in low-grade carcinomas and its poor reproducibility. METHODS: Spontaneously voided urine specimens from 40 patients with grade 1 (n = 27), grade 2 (n = 10), and grade 3 (n = 3) histologically proven transitional cell carcinoma and 40 patients with symptomatic urologic disease of the bladder were analyzed by cytology and DNA image cytometry. The DNA content was determined by use of the CM-1 Cytometer according to the guidelines in the ESACP Consensus Report on Standardization of DNA Image Cytometry. RESULTS: Urinary cytology yielded an overall sensitivity of 47.5%. Conventional analysis of DNA histograms measuring the presence of DNA stemline aneuploidy (1.8c > stemline ploidy [STP] > 2.2c) revealed a sensitivity of 62.5%; applying the stemline interpretation according to Böcking et al. increased the overall sensitivity to 75%. The specificity of both methods was 100%. DNA image cytometry demonstrated a high sensitivity in grade 1 tumors (70.4%) compared with cytology (26%). CONCLUSIONS: In light of its highly improved sensitivity compared with urinary cytology, DNA image cytometry should be used to evaluate suspect urothelial cells in urinary cytology specimens. Since the method provides more objective and reproducible results with a specificity comparable to that of cytology, we encourage its primary application in the screening for bladder cancer, provided these results can be confirmed in a multicenter evaluation study.

DNA-aneuploidy as marker for neoplasia in G1-urothelial carcinomas.

Biopsies from 60 grade-1 urothelial carcinomas and 50 normal bladder mucosae have been investigated by DNA-image-cytometry after enzymatic cell separation to determine the diagnostic sensitivity of DNA-aneuploidy for the identification of low grade urothelial neoplasia. Two different modes to detect DNA-aneuploidy were compared: the conventional application of a threshold at 2.2c for the modal DNA value and the use of the Kolmogoroff-Smirnow (KS) test to compare GO/1 phase fractions of the cells under analysis and the internal reference cells. Whereas the specificity for both types of analysis was 100%, the sentitivity of the latter method was 73.3% compared to 48.3% of the conventional procedure. Therefore, the application of the KS-test for the identification of DNA- stemlines as aneuploid results in an increased detection rate was compared with the conventional threshold procedure. The high prevalence of DNA- stemline aneuploidy even in low grade urothelial cancers may qualify this marker as a possible aid in the cytologic evaluation of urine and bladder washings.

Prostate-specific antigen immunoreactivity in spinal fluid.

OBJECTIVES: Prostate-specific antigen (PSA) is no longer believed to be tissue specific for prostate epithelial cells as it has been documented in various human tissues. The physiological role of PSA in this context is currently unknown. Furthermore the distribution of PSA throughout the human body remains to be established. We therefore investigated PSA immunoreactivity in human spinal fluid (SF). METHODS: The PSA concentration was measured in the SF and sera of 34 men and 6 women. The SF was obtained prior to spinal anesthesia and was kept frozen at -20 degrees C until analysis. RESULTS: PSA was detected in the SF of male patients. Median SF PSA was 0.03 ng/ml in the 34 men, whereas SF PSA was below the detection limit in the 6 women. In men we could establish a positive correlation between SF PSA and serum PSA with a correlation coefficient of r = 0.85 (p < 0.001). CONCLUSION: These results confirm recent literature reports indicating that PSA is detectable in various human tissues and fluids.

Detection of circulating prostatic cells during radical prostatectomy.

The detection of micrometastasis of prostate cancer could help to decide more appropriate therapeutic strategies in an individual patient. We have developed a flow cytometric method for detecting cytokeratin-positive cells in the peripheral blood before, during and after radical prostatectomy in patients with prostatic carcinoma. By means of this technique we were able to detect a higher number of cytokeratin-positive cells in the intraoperative blood sample than in the pre- and postoperative blood sample in 15 patients with prostate cancer (P < 0.05). Our results show an increase in the number of cytokeratin-positive cells with increasing tumor stage and grade, as well a good correlation of prostate-specific antigen (PSA) value with the number of cytokeratin-positive cells (r > 0.6). Our results underline the importance of no-touch techniques at prostatectomy to minimize release of tumor cells into the circulation during surgery. In the light of our results we consider that the indication for cell savers during radical prostatectomy should be reevaluated. The possibility of detecting single metastatic cells in peripheral blood will enable better individual patient management, and open up new modalities for diagnosing early prostate cancer and enhancing patient monitoring in relapse and tumor progression.

C-reactive protein as a marker for tissue damage in patients undergoing ESWL with or without retrograde stone manipulation.

In this study we attempt to evaluate the advantages and disadvantages of extracorporeal shock wave lithotripsy (ESWL) in situ versus retrograde stone manipulation before ESWL (ESWL+push back) in patients with proximal ureteral stones with regard to tissue damage and inflammatory processes. Several studies have revealed that C-reactive protein (CRP) is a useful marker for tissue damage and inflammation. Thirty patients following primary ESWL in situ, with residual calculi, were randomized to retreatment with ESWL in situ or ESWL+push back. Four of 15 patients in the ESWL+push back group demonstrated an increase in CRP levels after treatment compared with no significant increase in 15 patients in the ESWL in situ group. We conclude that ESWL+push back did not cause significantly higher CRP values than ESWL in situ. ESWL+push back may cause irritation, inflammation, and slight tissue damage in some cases; however, these effects are probably minor and would not contraindicate its use. The implications of this study are that serum CRP levels may be utilized to monitor tissue injury in patients undergoing auxiliary procedures.

Androgen responsiveness of stromal cells of the human prostate: regulation of cell proliferation and keratinocyte growth factor by androgen.

PURPOSE: Growth and development of the prostate are androgen dependent and mainly influenced by stromal-epithelial interaction. It is believed that indirect androgenic activation of paracrine factors like keratinocyte growth factor (KGF) in the prostatic stroma influences the growth of epithelial cells. In this study we investigated the role androgen plays in stromal cell growth and stimulation of KGF in the human prostate. MATERIALS AND METHODS: Stromal cells were derived from explant primary culture of human normal or benign prostatic tissue. The effect of different dihydrotestosterone (DHT) concentrations on cell proliferation was measured using 3[H]thymidine incorporation assay. The effect of DHT on levels of KGF protein was determined by Western blotting. The effect of DHT on levels of KGF gene expression was measured by various cycles of polymerase-chain-reaction (PCR) and multiplex PCR. RESULTS: Characterization of stromal cells showed epithelial cells less than 9.5% in all passages. DHT stimulated human prostate stromal cells in a dose dependent fashion over a concentration range of 0.001-10 nM. Immunocytochemical evaluation of KGF after DHT exposure showed a higher staining intensity. Relative quantitation of Western blotting showed a 1.93-fold increase in KGF protein in the androgen treated stromal cells. At 1 nM DHT conventional and multiplex PCR revealed a significant stimulation of the KGF mRNA expression. CONCLUSIONS: These data show for the first time that androgen stimulates cell proliferation as well as KGF protein and gene expression in human prostate stromal cells. This supports the hypothesis that androgen-induced stromal-derived KGF stimulates prostate epithelial cell growth.

Computed tomography for detection and staging of transitional cell carcinoma of the upper urinary tract.

A total of 91 patients were treated for upper tract urothelial tumors between 1981 and 1991. Preoperative computed tomography (CT) scans and nephroureterectomy for treatment of transitional cell carcinoma were performed in 26 patients. At pathological examination, 28 tumors were diagnosed of which 19 were in the renal pelvis and 7 were in the ureter. Intravenous pyelogram, retrograde and antegrade pyelogram detected 26 of 28 tumors (93%). CT detected 24 of 28 tumors (86%). However, CT is still the best current method for staging of upper urinary tract urothelial tumors, although staging was correct in only 5 of 9 T3 and T4 tumors.