[Urogenital tuberculosis and schistosomiasis (bilharzia) : Urological challenges in displaced persons]. / Urogenitaltuberkulose und Schistosomiasis (Bilharziose) : Urologische Herausforderungen durch Flucht und Vertreibung.

We are observing the largest worldwide wave of migration ever. Displaced persons usually do not have access to general health care and are faced with a lack of hygienic conditions and infection control while fleeing, which leads to an accumulation of "exotic" infectious diseases. The number of patients with tuberculosis (TB) had declined for many years in Germany; however, increasing numbers of cases have recently been observed. For urologists, of course, the manifestations of urogenital TB (UGTB) are of particular interest. Therefore, the basics regarding diagnosis and therapy of UGTB are discussed in this article and explained using case studies. The second important "exotic" infectious disease that urologists are increasingly facing is schistosomiasis. The larvae (found mostly in stagnant water) penetrate through intact human skin, mature and migrate into the liver, from where they immigrate into the venous capillaries of the intestine, the small pelvis, the bladder wall and the distal ureter, and there cause chronic inflammation. All urologists should be familiar with the diagnosis, therapy and prophylaxis of urogenital schistosomiasis and the oncogenesis of schistosomiasis-associated bladder carcinoma.

Thirty-eight years of stone meetings in Europe.

Of decisive importance for the many research groups all over Europe were the scientific symposia dealing with the theoretical foundations and clinical aspects of urinary stone disease. There were several sources from which today's European Urinary Stone meetings and the "Eurolithiasis Society" itself arose. It was a long way from Leeds in 1968 to Jena 1970, Bonn-Vienna in 1972 and to 11 European meetings from 1989 to 2005. Which developments in urinary stone disease research have been presented at our congresses during the past 40 years? The 1970s and 1980s are the years marked by efforts to measure the important lithogenic substances such as calcium, ionized calcium, uric acid, phosphate, oxalate with reliable methods. Hypercalciuria and specifically mild hyperoxaluria were the topics of numerous investigations in the 1970s, 1980s and 1990s. The calcium-loading test described by Pak has been discussed frequently since its application. It became apparent that oxalic acid is more important in urinary stone formation than hypercalciuria. Of importance were investigations done by Robertson and his colleagues on the influence of diet (in particular, an animal protein-rich diet) on urinary stone formation. Another emphasis of research was investigation of the crystallization process: supersaturation, crystal growth and aggregation are important steps in urinary stone formation. Of great importance in the formation of urinary stones are inhibitors (inhibitory activity): citrate, magnesium, pyrophosphate, macromolecules: GAGs, THP etc. and it became possible in the early 1970s to determine substances such as Tamm-Horsfall protein (THP) and GAGs. Much attention in the 1970s and 1980s was focused on urinary stone analysis (X-ray diffraction, infrared spectroscopy, polarization microscopy) and standardization of these methods. In the mid-1980s, a whole series of epidemiological studies were carried out, with data for the Federal Republic of Germany, East Germany, Czechoslovakia and Austria. The search for "stone-removing" medications, their description and clinical use was the subject of much clinical research and in vitro examinations. A definite advance occurred in the 1980s with the development of new instrumental technologies for the management of urinary stones such as shockwave ("Stosswelle") lithotripsy, percutaneous nephrolithotomy and ureterorenoscopy (" breakthrough innovations"). Since the 8th European Urolithiasis Symposium there have regularly been presentations pertaining to the topic of the molecular basis of inherited lithiasis. The last 10-15 years have shown an increasing turning toward the importance of cellular alterations and supersaturation and their relation to stone formation. In conclusion, I would like to note that it is of decisive importance for the research groups all over Europe to organize scientific symposia dealing with the theoretical foundations and clinical aspects of urinary stone disease under the protection of the European Urolithiasis Society.

[Urological specialist opinion in medical law]. / Das urologische Fachgutachten im Arztrecht.

The role of specialist opinion in medical law (medical standards and the determination of due care) is discussed. The mandator is usually a court of law or an arbitral committee of the general medical council. In comparison to other countries, a specialist opinion is judicially ordered. An increase in the number of patient accusations against the medical practitioner must be shown. The form and preconditions for a urological specialist opinion in medical law are given. The requirements for the specialist are comprehendability, readiness to give objective answers to the questions presented as well as careful research into the development of the illness. Reference is also made to the responsibility of teaching hospitals to provide education on producing a specialist opinion within the framework of specialist training. An overview of the common complications in the diagnosis and therapy of typical urological illnesses, which could lead to medical disputes, is presented. Important sources of error, as well as contravention of the clarification and counselling responsibilities, are presented synoptically.

Renal tubular alteration by crystalluria in stone disease-an experimental study by means of MDCK cells.

OBJECTIVES: Physicochemical properties of urine do not explain the formation of urinary stones. Clinical findings and results of animal experiments suggest that alteration to the renal tubular cell plays a key role in the initiation of urinary stone formation. It is not clear whether this is a primarily intracellular alteration of metabolic origin which, after lysis of the renal tubular cell in the lumen, presents a nucleus for the formation of concretions, or whether in the lumen it is tubular cell damage induced by crystalluria that triggers the formation of urinary stones. MATERIALS AND METHOD: Using Madin-Darby canine kidney cells, the influence of crystalluria on the renal tubular cell was tested in cell cultures. The influence of parathyroid hormone, vitamin D(3), oxalate and calcium concentrations and the extent to which these processes can be inhibited by allopurinol and selenium were investigated. RESULTS: Calcium oxalate monohydrate crystals produced reproducible damage to the renal tubular cell which was independent of parathyroid hormone and vitamin D(3). The crystalluria-induced effects were unrelated to the oxalate and calcium concentration or the pH. Allopurinol and selenium were able to inhibit the processes. CONCLUSION: The results indicate secondary involvement of the renal tubular cell in lithogenesis as a result of luminal alteration caused by calcium oxalate crystals. Mechanical damage and interaction between crystal and tubular cell lead to the apposition of crystals. The nephroprotective effect of allopurinol and selenium as antioxidants might explain the benefit of allopurinol found clinically in terms of stone metaphylaxis.

[ImmunoCyt--a new urine test in diagnosis of bladder cancer]. / Urinzytologie beim Harnblasenkarzinom. Diagnostische Wertigkeit eines neuen immunologischen Fluoreszenztestes.

ImmunoCyt is a new immunocytologic fluorescence test promising a higher diagnostic sensitivity, esp. for TaG1 carcinomas. The aim of the study was to evaluate the sensitivity of the test in diagnosis of bladder cancer as compared to both urinary cytology and histopathology. A total of 121 spontaneous urine samples of 92 patients (age range 28 to 86, mean 62.5 years) was examined. 41 of the samples were of patients suspicious of transitional cell carcinoma, 46 of patients in whom symptoms were suggestive of tumor recurrence, and 34 of patients who were part of a follow-up protocol. Cystoscopy was performed in all patients. The ImmunoCyt-test was carried out according to the manufacturers protocol using 3 fluorescent monoclonal antibodies. A total of 113 specimens could be evaluated. In 87 cystoscopy and/or histology was negative (control group). There was histologic evidence of 7 pTaG1, 4 pTaG2, 8 pT1G2/G3, and 7 pT2G2/G3 bladder cancers. As for ImmunoCyt and cytology specificity was 83.9% and 91.9%, resp. The combined specificity was 81.6%. Sensitivity amounted to 38.5% and 34.6%, resp., the combined sensitivity to 53.8%. Sensitivity for TaG1 carcinomas was 14.3% each, for TaG2 carcinomas 25% and 50%, for T1G2/G3 carcinomas 37.5% each, and for T2G2/G3 carcinomas 71.4% and 42.9%, resp. In our study the ImmunoCyt test did not show the expected increase in the detection of TaG1 bladder cancers. Because of false-positive results the test should only be used in combination with urinary cytology which reveals a higher specificity. In conclusion the ImmunoCyt test can not replace cystoscopy (with biopsy) in diagnosis and monitoring of bladder cancer.

[Infection-induced urinary stones]. / Infektinduzierte Harnsteine.

Infection stones make up approximately 15% of urinary stone diseases and are thus an important group. These stones are composed of struvite and/or carbonate apatite. The basic precondition for the formation of infection stones is a urease-positive urinary tract infection. Urease is necessary to split urea into ammonia and CO(2). As a result, ammonia ions can form and at the same time alkaline urine develops, both being preconditions for the formation of struvite and carbonate apatite crystals. When these crystals are deposited infection stones form. Pathogenetically, various risk factors play a role: urinary obstruction, neurogenic bladder, dRTA, and MSK. If these infections are not treated and the stones are not removed, the kidney will be damaged. Modern methods are available for stone removal, e.g., ESWL and/or instrumental urinary stone removal. Here, especially less invasive methods are preferable. Any treatment must be adjusted to the patient individually. Patients should be examined frequently for recurrent urinary tract infections and stone recurrences, and new infections must be resolutely treated. Good therapy and prophylaxis are possible with present-day treatment modalities.

Urinary infection stones.

Infection stones make up approximately 15% of urinary stone diseases and are thus an important group. These stones are composed of struvite and/or carbonate apatite. The basic precondition for the formation of infection stones is a urease positive urinary tract infection. Urease is necessary to split urea to ammonia and CO(2). As a result, ammonia ions can form and at the same time alkaline urine develops, both being preconditions for the formation of struvite and carbonate apatite crystals. When these crystals deposit themselves infection stones form. If these infections are not treated and the stones are not removed, the kidney will be damaged. For stone removal modern methods are available, e.g. ESWL and/or instrumental urinary stone removal. Here especially less invasive methods are preferable. Any treatment must be adjusted to the patient individually. Patients should be examined frequently for recurrent urinary tract infections and stone recurrences and, newly arising infections must be resolutely treated. Good therapy and prophylaxis are possible with present-day treatment modalities.

Collagen fleece for defect coverage following plaque excision in patients with Peyronie's disease.

OBJECTIVES: Surgical correction of penile deviation in patients with Peyronie's disease by tunical plication often leads to shortening of the penis. It is, thus, recommendable to combine tunical plication with plaque incision or excision. The resulting tunical defect, however, requires grafting, and various techniques have been described. In comparison with tunical plication, all of these combined techniques are associated with increased operation time, mainly due to additional procedures necessary at the donor site, and may result in defects at the donor site. We here report a novel surgical technique by which tunical defects after partial excision of plaques are covered by a ready-to-use collagen fleece coated with tissue sealant (TachoComb). METHOD: A prospective clinical observation trial was conducted in 19 patients with penile deviation due to Peyronie's disease. RESULTS: In all patients, a reliable closure of the Tunica albuginea was achieved, and no postoperative haematoma formation was observed. Postoperatively, none of the patients suffered from erectile dysfunction. During the follow-up period of 25 months, objective and subjective improvement was 83% and 72%, respectively. CONCLUSION: The present data indicate that this novel surgical technique may be of benefit in patients with Peyronie's disease and should thus be further evaluated.

Comparison of cytology and nuclear matrix protein 22 for the detection and follow-up of bladder cancer.

OBJECTIVES: This study was designed to determine the clinical usefulness of the nuclear matrix METHODS: 84 patients suffering from bladder cancer or suspected bladder cancer, 25 patients with benign urological lesions and 60 healthy controls participated in a prospective study. Freshly voided spot urine samples were taken for cytological examination and determination of NMP 22 levels by enzyme-linked immunoassay. RESULTS: The sensitivity of the NMP 22 test according to the tumor grading was (results of cytology in brackets): G1 25.0% (20.0%); G2 68.2% (59.1%), and G3 100.0% (66.7); overall sensitivity was 62.5% (45.0%). The sensitivity for superficial bladder cancer was 46.7% (36.7%) and for invasive bladder cancer 90.0% (70.0%). The specificity was 65.9% (88.9%). CONCLUSIONS: NMP 22 is a reliable tool for detecting invasive bladder cancer. Results for the frequently occurring low grade superficial bladder cancer are as poor as those obtained with cytology. In addition benign lesions such as urolithiasis or urinary tract infection lead to false-positive results. Therefore cystoscopy has to be performed when trying to detect and follow-up bladder cancer.

Schistosomiasis: a critical review.

Precise data on epidemiology, morbidity, post-treatment resolution, reinfection, and resurgence of schistosomiasis could be helpful in establishing purposeful treatment plans for the disease in endemic populations. Here we give a concise overview of recent publications on bilharziasis. A main emphasis is placed on studies on the prevalence of schistosomiasis, partly including long term surveillance of morbidity following treatment with praziquantel. As genito-urinary schistosomiasis may be a risk factor for the spread of HIV, the involvement of the reproductive tract has become another focus in research on the disease. A novel diagnostic tool, eosinophil cationic protein (ECP), is proposed to correlate with the degree of inflammation of the genito-urinary tract.

[Molecular biology of cystinuria]. / Molekularbiologie der Zystinurie.

Cystine stones belong to the kidney stones diseases which are difficult to manage due to the high rate of recidivation and the necessary surgical procedures. Cystinuria is an autosomal recessive defect of the transport of cystine and the dibasic amino acids in the proximal kidney tube. Recently, two subunits of a renal cystine transporter have been identified. Mutations in these genes have been shown to lead to the cystinuria phenotype. Genetic and functional analyses have helped to modify the classification of cystinuria which had previously been exclusively based on biochemical data. Furthermore, first steps towards a molecular genetic testing have been carried out replacing the so far diagnostic procedure which are stressing for the patients. The results of these testings make an individual therapy possible.

Minimally invasive PCNL in patients with renal pelvic and calyceal stones.

Stones of the renal pelvis can be treated either by extracorporeal shock wave lithotripsy (SWL) or percutaneous nephrolithotomy (PCNL). As a low-risk procedure with a longer treatment period, SWL often leads to persistent residual stone fragments, whereas conventional PCNL achieves a higher stone-free rate and allows a shorter treatment period albeit with a somewhat higher surgical risk. To reduce the invasiveness of conventional PCNL, the application of a miniaturised instrument for PCNL (MPCNL) was evaluated. For MPCNL a rigid nephroscope with a calibre of 12 F was developed and used in 19 patients. After puncture of the kidney under ultrasound control and single-step dilatation, a 15 F Amplatz sheath was placed. Data on the stone size and location, stone-free rate, blood transfusions, operating time and complications were recorded. In all patients, the part of the kidney afflicted by the stone was successfully punctured. On average, retreatment rate was 0.7. The mean stone size was 2.4 cm(2). The average operating time was 99.2 min. In every case, the absence of residual stones was confirmed radiologically and nephroscopically. Hemorrhages requiring a blood transfusion did not occur. A febrile pyelonephritis occurred as a postoperative complication in one patient (= 5.3%). MPCNL represents an alternative to SWL for renal calculi with a size from 1 to 2 cm located in the renal pelvis and calices, especially the lower calix. The advantages are the short treatment time, the high stone-free rate and the accessibility of lower pole stones which are less amenable to SWL. MPCNL is not suitable for large concrements since the limited sheath diameter would increase the operating time. Due to this limitation, MPCNL represents an extension of the indication for conventional PCNL that it can in no way replace.

Arterial blood pressure following different types of urinary stone therapy. Presented at the 8th European Symposium on Urolithiasis, Parma, Italy, 1999.

OBJECTIVE: Several studies reported increased blood pressure (BP) values following extracorporeal shock wave lithotripsy (ESWL) treatment of renal stones. It is unclear, however, whether this is due to ESWL, since nephrolithiasis itself increases the relative risk of developing hypertension. Therefore we prospectively studied the BPs of stone patients undergoing different types of treatment. METHODS: 252 stone patients (63% males, 37% females, median age 44.3, range 11.7-86.4 years) participated. 168 suffered from uretral stones: 50 underwent ESWL; 40 ureteroscopy, and 78 patients passed stones spontaneously (SP). 84 had renal stones: 60 underwent ESWL; 8 percutaneous nephrolithotomy/open surgery, and 16 no treatment. Systolic (SBP) and diastolic (DBP) BP were measured according to Riva-Rocci prior to, immediately after, and 3, 6, 12, 18 and 24 months after stone therapy. RESULTS: Immediately after SP, SBP decreases, whereas after active stone treatment increases (highest after ESWL) in SBP were seen. DBP was unchanged. During the further follow-up, a gradual increase in BP was observed in all groups. At 24 months in all groups, regardless of the stone location and type of treatment, SBP and DBP were significantly higher than the pretreatment levels (p = 0.000). There was no a difference between renal and ureteral stones, or between the ESWL treatment and the other groups. CONCLUSION: Renal stone disease itself rather than the type of treatment significantly increases SBP and DBP during a follow-up period of 24 months. The underlying mechanisms remain to be elucidated.

Comparison of symptoms, morphological, microbiological and urodynamic findings in patients with chronic prostatitis/pelvic pain syndrome. Is it possible to differentiate separate categories?

164 patients with prostatitic symptoms were evaluated by segmented urinalysis and culture and classified according to the National Institutes of Health classification system: 64 patients (38%) suffered from chronic bacterial prostatitis; 12 (7%) from inflammatory chronic pelvic pain syndrome, and 92 (55%) from non-inflammatory chronic pelvic pain syndrome. Transrectal ultrasound of the prostate, uroflowmetry and measurement of residual urine were also performed. Complaints were recorded using a questionnaire. Our studies revealed that leukocytes in expressed prostatic secretions could be detected in only 24 and 36% of patients with positive bacterial or chlamydial culture. Complaints, ultrasound and urodynamic findings were similar in the 3 groups. Therefore the differential diagnosis and therapy, based on the results of the 4-glass test and cultures as well as on transrectal ultrasound of the prostate, seem to be difficult.

[Early detection of prostatic carcinoma in urologic practice with digital rectal examination and prostate-specific antigen. Early Detection Project Group]. / Früherkennung des Prostatakarzinoms in der urologischen Praxis mit digitaler rektaler Untersuchung und prostataspezifischem Antigen. Projektgruppe Früherkennung.

For the early detection of prostate cancer, a patient should undergo digital rectal examination (DRE) and PSA investigation. Follow-up of increased PSA levels detects nearly 80% of cancers. Positive predictive value of suspicious DRE and PSA is about 50%. Whereas in the first evaluation of this case-finding trial about 70% of the patients had organ-confined cancers, nearly all of the detected cancers in the follow-up investigation were organ confined. The increased number of organ-confined cancers detected in early periodical examinations can lead to a reduction of mortality and morbidity from prostate cancer.

Molecular genetic methods in the diagnosis of invasive bladder cancer.

Development and progression of tumours is generally driven by an accumulation of genetic alterations. In this study we correlated chromosome 17 aneuploidy to invasiveness of bladder cancer by the method of fluorescence in situ hybridisation (FISH) in urinary cytospins. We investigated the value of FISH compared to DNA cytophotometry in the diagnosis of bladder cancer. 39 patients with or suspicious for bladder tumour were analyzed. 19 patients had a bladder tumor at the time of diagnosis, 14 superficial (Ta-T1) and 5 invasive (T2-3). The remaining 20 patients had no tumour at the time of diagnosis, however 9 of them had one in prehistory (Ta-T2). For FISH we used the DNA probe of HER-2/neu located on chromosome 17. DNA image cytometry was performed according to single cell interpretation of Böcking. Our results showed a correlation between HER-2/neu CEP 17 alterations and invasive bladder cancer to the extent of 10-70% aberrant cells for patients with current invasive bladder tumour as well as for patients who had been cured but with as invasive bladder cancer in prehistory. On the other hand, the percentage of aneuploid cells for negative biopsy and superficial tumour was 0-2%. The DNA cytophotometry brought an uniform aneuploidy only for present invasive tumours: negative biopsies, superficial cancer and invasive tumour just in prehistory, showed mixed diploid-aneuploid DNA patterns. Our results showed that for the detection of aberrant tumour cells the method of FISH is more sensitive than DNA cytometry. FISH could provide important information in the prognosis of bladder cancer.

Immunohistochemical examinations (Ki67, p53, nm23) and DNA cytophotometry in bladder cancer.

Bladder cancer is clinically characterized by a high recurrence rate for superficial tumours up to 70% and by the invasiveness of advanced bladder cancer. To learn more about the biological behaviour of an individual bladder cancer different tumour markers have been investigated. The aim of our study was to compare the potential of aggression of both superficial and invasive bladder tumours by means of the proliferation marker Ki67, the tumour suppressor gene p53, the non metastasizing protein nm23 and the evaluation of DNA ploidy. We examined 36 patients, 28 with a bladder tumour (Ta-T4) and 8 without as a control group. For immunohistochemistry (Ki67, p53, nm23) we took paraffin sections and scored semiquantitatively under a microscope. The DNA cytophotometry was done on bladder washings by evaluating the DNA ploidy of single cells. The results showed that benign tissues were negative for Ki67 and p53 but positive for nm23. The DNA diagnosis was diploid for all benign samples. The superficial bladder cancer (Ta, T1) showed, in comparison to the invasive tumours, significantly lower numbers of aneuploid cells and a higher rate of p53 mutations. On the other hand the invasive tumours (T2-4) were correlated to significantly higher proliferation rates and higher potencies for metastasizing. The combination of the investigated tumour markers allowed a graduation of the biological behavior of an individual bladder cancer. Especially a high p53 mutation rate and a non aneuploid DNA diagnosis were indicators for the recurrence of superficial bladder tumours. Invasive growth of bladder cancer was characterized by high Ki67 proliferation and low nm23 protein binding.

Serologic angiogenesis factors and microvascular density in renal cell carcinoma: two independent parameters.

Renal Cell Carcinoma (RCC) is characterized by high intratumoral microvascular density (iMVD) and significantly elevated serologic titers of angiogenesis factors, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (vEGF) and angiogenin (Ag). The goal of the present study was to find whether a correlation exists between any of these factors and intratumoral microvascular density (iMVD). Serologic angiogenesis factors were determined directly before nephrectomy of a tumorous kidney in 12 patients (average age: 67.6 years [49-78] with localized clear-cell RCC (Robson I-II) (Quantikine', R&D Systems Europe, Abington, UK). Sections were taken in each case from the microscopically most aggressive area of the tumorous kidney preparations. Staining was carried out with a primary antibody against CD31 (DAKO M 0823, Hamburg, Germany). iMVD was counted at 160x magnification at five "hot spots" 200 x 200 microns in size, and the individual factors were then correlated with the areas of maximum and average iMVD (iMVDmax, iMVD-d). Average concentrations of 38 pg/ml +/- 68 were found for bFGF, 712 pg/ml +/- 791 for vEGF, and 358 ng/ml +/- 97 for Ag. iMVDmax was 20 +/- 11 per area, iMVD-d was 410/mm2 +/- 243. No correlation was found between microvascular density and serologic angiogenesis factors for any parameter. Actual tumor vascularization, expressed as iMVD, was not correlated with the 3 angiogenesis parameters which were studied. On the one hand, this raises the question whether angiogenesis can be measured at all with these parameters; on the other, it remains nuclear whether the continuous process of angiogenesis can be registered at all by chronologic, specific factor analysis.