[The life and works of Professor Max Hösel (1906-1971): a pioneer of endoscopic prostate surgery]. / Das Leben und Wirken von Professor Max Hösel (1906-1971) : Ein Pionier der endoskopischen Prostatachirurgie.

In 1949 Max Hösel (1906-1971) founded the largest urological hospital in the world at that time in the former military hospital in Ulm, which at times had over 250 inpatient beds. In the south German region he had at his disposal the most comprehensive endoscopic operation collective and the greatest experience in transurethral resection of the prostate (TUR-P). From 1948 to 1958 he carried out approximately 13,850 prostate resections with an average adenoma weight of 30 g and a mortality rate of <1%. The technical inadequacies of the resection instruments at that time prompted Hösel to develop a new form of resectoscope, namely the type 782. This resectoscope allowed a fast and complete resection of prostatic adenomas due to the improved visual field and better handling (rotating the operational unit) and also made the transurethral resection of larger prostatic adenomas possible. Therefore, in "Ulm and around Ulm" substantially larger prostatic adenomas could be endoscopically treated and open enucleation was not necessary. Prof. Hösel was an international force as a urologist and in Germany was ranked as one of the pioneers in the field of endoscopic prostate surgery. Although he never held the position of a University Chair, in the municipal hospitals in Ulm he accomplished the foundations for the later University Clinic for Urology.

[Histopathology reports of findings of prostate needle biopsies. Individual treatment]. / Histopathologische Befundberichte von Prostatastanzbiopsien. Individuelle Behandlungskonzepte.

OBJECTIVES: This survey-based study examined which information urologists extract from prostate needle biopsy reports and what is needed for clinical management of prostate cancer patients. MATERIAL AND METHODS: A questionnaire was developed to investigate several topics related to prostate cancer biopsies and four different clinical situations were explored separately, depending on whether the urologist intended a curative or palliative treatment. RESULTS: A total of 95 out of 282 (33 %) urologists responded to the questionnaire and returned anonymous responses. On average the participants had a professional career of 13 years (range 6 months to 38 years), 22 (23 %) urologists performed radical prostatectomy, 73 (77 %) were not surgically active, 55 (58 %) took 10-12 scores within the framework of the proposed first biopsy setting, 32 (34 %) took 6-8 scores and 6 (6 %) > 12 scores. Urologists with a professional career <15 years took significantly more biopsies. The primary and secondary Gleason patterns were required for only 36 (38 %) respondents to make treatment decisions. In prostate needle biopsies containing only a single focus of prostate cancer only 44 (48 %) of the respondents would request a Gleason score if not provided in the initial report. In addition to the Gleason score other information used by urologists to make treatment decisions included perineural invasion (60 %), periprostatic infiltration (57 %), extraprostatic spread (57 %) and the percentage of core involvement by cancer (13 %). Interestingly, in biopsies with multiple positive cores from separate locations 84 out of 95 urologists (88 %) used the highest Gleason grade to determine the treatment plan. The term atypical small acinar proliferation (ASAP) was uniformly considered sufficient to retake biopsies by 44 % (42/92) of urologists and only 53 % (49/92) of urologists performed rebiopsies in the case of high grade prostatic intraepithelial neoplasia (PIN). CONCLUSION: In this sample of 95 urologists there was high variability in the way clinicians used prostate needle biopsy pathology reports. The results of this survey underline that improved communication between urologists and pathologists is necessary.

[Renal masses in pregnancy. Diagnostics and therapeutic management]. / Nierentumore in der Schwangerschaft. Diagnostik und therapeutisches Management.

Cancer is the second most common cause of death in women of childbearing age. However, renal cell carcinoma (RCC) is a rare tumor in this collective with an incidence far below 5/100,000 cases per year. Therefore, medical experience with respect to diagnostics and therapeutic management of newly diagnosed RCC in pregnant women is scarce and the number of published cases low. However, recent studies indicated that higher estrogen levels and multigravidity could be associated with a higher risk of RCC. The aim of this article is to summarize the clinical experience in treating pregnant women with renal cancer against the background of those cases published in the literature.

[Prevention, early diagnosis and treatment of chemoextravasation. Practical management in the uro-oncological practice]. / Prävention, Früherkennung und Behandlung von Zytostatikaparavasaten. Praktisches Management in der uroonkologischen Praxis.

Extravasation of chemotherapeutic agents is a rare (1-6%) but potentially severe iatrogenic complication of systemic therapy. Depending on the cytotoxic agent, tissue damage and necrosis may occur, followed by a delay in administration of chemotherapy, prolonged hospitalization, impaired function, and the need for tissue excision. Therefore, optimal placement of the intravenous catheter is absolutely necessary to reduce the risk of extravasation. The aim of this report is to give urologists a practical and useful guide on how to prevent, diagnose, and treat this complication.

[Systemic therapy of metastatic renal cell carcinoma: from many options to the therapeutic strategy]. / Systemtherapie des metastasierten Nierenzellkarzinoms : Von der Vielzahl der Möglichkeiten zur therapeutischen Strategie.

In the last 5 years the paradigms for the treatment of metastatic renal cell cancer have fundamentally changed. Until 2005 systemic therapy was limited to the immunomodulating cytokines interferon-alfa and interleukin-2, in recent years, however, tyrosine kinase inhibitors, mTor inhibitors and monoclonal antibodies have been established for this therapeutic situation. Without validated predictive biomarkers it is currently not possible to select patients who are likely to benefit from a certain therapy. Therefore, most current guidelines stratify the patients into risk groups according to the MSKCC risk score. The resulting treatment algorithm for first-line therapy is limited to these new drugs within all risk groups. Since approval for more tyrosine kinase inhibitors and mTOR inhibitors is currently awaited, the number of treatment options will expand further in the near future. The present paper reviews the present study data and aims to provide practical advice for the treatment of patients suffering from metastatic renal cell cancer.

[Intravesical therapy in non-muscle-invasive bladder cancer: indications and practical considerations]. / Intravesikale Therapie beim nicht muskelinvasiven Urothelkarzinom der Harnblase : Indikation und praktisches Management.

Intravesical treatment with various agents is an accepted standard for treating patients with non-muscle-invasive bladder cancer; all guidelines recommend its use. Depending on the agent and the instillation schedule, a reduction in recurrence and a decrease in the progression rate can be achieved.However, many of the recommendations in the various guidelines are currently under debate. Early instillation with a chemotherapeutic agent is probably overtreatment in patients requiring further induction or maintenance therapy because it adds no further benefit. The economic aspects of early instillations are also being discussed. Recent studies question the ability of bacillus Calmette-Guérin (BCG) instillations to reduce the progression of non-muscle-invasive bladder cancer. Furthermore, the superiority of maintenance therapies compared with induction schedules is under debate.There is a great body of evidence that the effectiveness of intravesical chemotherapy can be increased by simple measures. Reduction of BCG side effects without compromising the oncological outcome is possible.

[Complementary medicine in oncology]. / Komplementärmedizin in der Onkologie.

In cancer therapy vastly different kinds of treatment regimens, but as a rule scientifically validated and reviewed, play a central role dependent on the tumor entity. Besides the options of schoolbook medicine complementary, alternative and supportive treatment options are becoming more frequently used in routine clinical practice. Numerous concepts and agents, partly verified in studies and partly based on empirical experiences are being applied. It is our intention to give a survey of the most common agents and concepts and to point out the risks and capabilities.

[Palliative systemic therapy of castration-resistant prostate cancer: current developments]. / Palliative Systemtherapie des kastrationsresistenten Prostatakarzinoms : Aktuelle Entwicklungen.

Androgen withdrawal or surgical castration remains the standard therapy for advanced prostate cancer disease. Even for castration-resistant prostate cancer the therapeutic option of docetaxel-based chemotherapy is well studied and defined. Facing disease progression after docetaxel-based therapy there are multiple options to continue therapy but the evidence level is rather poor. In the last few years targeted therapy and immunomodulation have been the focus of clinical trials. The presented manuscript intends to provide an overview of classical cytostatic agents, endothelin inhibitors, immunotherapy, modified hormone therapy, multikinase inhibitors and radionuclide approaches which are currently under investigation for implementation in the clinical setting.

[Testosterone replacement therapy and prostate cancer. The current position 67 years after the Huggins myth]. / Testosteronsubstitution und Prostatakarzinom. Eine Standortbestimmung 67 Jahre nach dem Huggins-Mythos.

Hypogonadism is highly prevalent in the elderly and in men with prostate cancer. Symptoms of hypogonadism, such as depression, lack of libido, and decreased bone mineral density, can significantly impair quality of life. In addition, testosterone plays an important role in erectile preservation and in growth and function of the cavernosal and penile nerves. There are compelling data showing that testosterone replacement therapy (TRT) does not increase the risk of prostate cancer. The literature (four published studies) concerning men treated with TRT after definitive therapy for prostate cancer reports only one biochemical recurrence. Based on these data, physicians cannot really justify withholding TRT from symptomatic patients after they have been successful treated for prostate cancer. This review gives the practising urologist an overview of the latest literature and useful advice on this controversial topic.

Transrectal ultrasound as diagnostic tool for the detection of local recurrence following cystectomy and urinary diversion.

OBJECTIVE: Routine follow-up after cystectomy for bladder cancer detect patients with local recurrence late in the course of disease. We set out to determine the value of transrectal ultrasound (TRUS) as diagnostic tool to diagnose local failure. PATIENTS AND METHODS: Between 1986 and 2003, radical cystectomy for bladder cancer with orthotopic diversion was performed in 642 male patients. We identified all patients that simultaneously had transabdominal ultrasound, digital rectal examination, TRUS and CT/MRI of the pelvis at the diagnosis of local recurrence. RESULTS: Mean follow-up was 59.4 months. 83/642 patients (13%) had local failure of bladder cancer during follow-up. In 48/642 patients (7.5%) the local recurrence was the first site of recurrence. 35/642 patients (5.5%) developed local failure with concomitant distant disease. 31/83 patients met the inclusion criteria. The median time between cystectomy and diagnosis of local recurrence was 13 months (2-51 months). Routine follow-up detected local recurrence in 1 asymptomatic patient. 25/31, 3/31 and 2/31 patients had pain in the lower extremities/pelvis, hematuria and urinary retention, respectively. Digital rectal examination, transabdominal ultrasound, TRUS, and CT/MRI of the pelvis were suspicious for local recurrence in 9, 7, 26, and 29 patients, respectively. CONCLUSIONS: TRUS is a highly sensitive tool in detecting local recurrence following cystectomy. It is easy to perform and inexpensive. We recommend TRUS in short intervals in all patients with high risk for local recurrence in order to detect cancer early.

[Role of androgen receptors in hormone-refractory prostate cancer: molecular basics and experimental therapy approaches]. / Die Rolle des Androgenrezeptors im hormonrefraktären Prostatakarzinom : Molekulare Grundlagen und experimentelle Therapieansätze.

The development of hormone-refractory prostate cancer cells is one of the major causes for the progression and high mortality rates in advanced prostate cancer (PCA). While the loss of the androgen receptor (AR) is the predominant mechanism for development of a hormone-insensitive disease in vitro, the first in vivo studies showed that the AR is still expressed or is even overexpressed in hormone-refractory PCA. In view of the increasing cases of PCA in the industrialized Western countries, a series of cell and molecular biological studies has led to the identification of various new factors and mechanisms that play a role during the development of hormone-refractory tumors. These findings should lead to the development of new therapeutic strategies.

[Systemic therapy approaches in patients with bone metastases of urogenital malignancies]. / Systemische Therapieansätze bei Knochenmetastasen urogenitaler Tumoren.

Bone metastases develop commonly in patients with a variety of urogenital malignancies and are a major cause of morbidity and diminished quality of life in a significant proportion of urogenital carcinoma patients. For example, bone metastases occur in approximately 80% of patients with hormone-refractory prostate cancer and in approximately 25% of patients with renal cell carcinoma. A sufficient and early therapy is crucial since adequate therapy can lead to significant improvements in pain control and function and maintain skeletal integrity. The effective treatment of bone metastases requires multidisciplinary cooperation between urologists, oncologists, surgeons, nuclear medicine physicians and radiation oncologists. Analgesic measures, bisphosphonates, radionuclides, radiation therapy as well as surgical procedures are available. This review will focus mainly on the role of analgetics, bisphosphonates, radionuclides and radiolabelled bisphosphonates in the treatment of bone metastases.

Clinical value of transrectal ultrasound in the diagnosis of suspected neoplasia in the small pelvis.

PURPOSE: In daily clinical practice, it is challenging to accurately diagnose suspected neoplasias in the small pelvis by minimal invasive means, and CT-guided biopsy is often limited in its feasibility. The aim of our study was to evaluate whether transrectal ultrasound (TRUS)-guided biopsy can verify suspected neoplasias in the small pelvis histologically. MATERIAL AND METHODS: The study population consisted of 12 patients who underwent biopsy of suspected malignancy in the pelvis by TRUS. All patients had clinical signs of an advanced tumour stage and in all cases, biopsy utilising computerised tomography (CT scan) had been unsuccessful despite of a documented lesion on CT scan or magnetic resonance imaging. For the TRUS guided biopsy, a commercially available 3-dimensional 7.5-MHz-probe was used (Combison 530 D, GENERAL ELECTRIC, Milwaukee, USA). The probe was armed with an 18 G biopsy gun. RESULTS: In all patients, the suspected lesion was easily detectable by TRUS, and tissue for verification of the malignant origin of the lesions could be collected under real-time TRUS with only 2 patients needing anaesthesia. The biopsy cores were of excellent quality and adequate for conclusive pathological diagnosis. 6 cases of lymph node metastases of a transitional cell carcinoma were detected. 1 case of extended node metastasis in prostate cancer, 1 paravesical manifestation of recurrent cervical cancer, 1 metastasis of a paravesically infiltrating colon cancer and 2 cases of paravesical metastases of a gastric cancer were also diagnosed. In one case, extragenital endometriosis could be diagnosed. CONCLUSION: Based on our experience it can be stated that TRUS-guided biopsy is a reliable diagnostic tool for verification of the neoplastic origin of suspected masses in the small pelvis. In all cases with a history of unsuccessful CT guided biopsy, sufficient tissue cores for conclusive histology could be collected with our technique, and surgical exploration could be avoided. This technique is minimally invasive, without radiation exposure, well tolerated under analgesia, time efficient and cheap.

[Ureteral stricture after extracorporeal shock wave lithotripsy. Case report and overview of the spectrum of rare side effects of modern ESWL treatment]. / Ureterstriktur nach extrakorporaler Stosswellenlithotripsie. Kasuistik und Ubersicht über das Spektrum seltener Nebenwirkungen der modernen ESWL-Therapie.

Extracorporeal shock wave lithotripsy (ESWL) is considered a very safe and noninvasive procedure for the treatment of urolithiasis. Achievements in the technical development of recent decades resulted in a continuous reduction of side effects. One of our patients, a woman with cystinuria, developed a temporary ureteral stricture after several sessions of ESWL. Encouraged by this observation we set out to explore--based on a MEDLINE literature search--published reports of more severe side effects observed in modern ESWL therapy. Besides hydronephrosis and renal colic the most common side effects were renal and perirenal hematomas in up to 4% in the larger series. Uncommon extrarenal complications are described mostly in case reports, which are also outlined in this report. The injury of visceral organs (liver, spleen, gut, pancreas) was published most frequently. A rupture or dissection of an abdominal aortic aneurysm as an outstanding serious complication was also reported several times. Taking obvious and well-known contraindications into consideration and carefully preparing the patients for the therapy (i.e., checking hemostasis, drug history), ESWL is a very safe procedure with a low risk of serious complications. Yet, postoperative clinical and ultrasound monitoring seems to be essential especially with respect to the increasing numbers of outpatient procedures.

Nitric oxide-mediated inhibition of androgen receptor activity: possible implications for prostate cancer progression.

Chronic inflammation increases the risk of cancer and many cancers, including prostate cancer, arise at sites of chronic inflammation. Inducible nitric oxide synthase (iNOS) is an enzyme dominantly expressed during inflammatory reactions. Although synthesis of high amounts of nitric oxide (NO) by iNOS has been demonstrated in pathophysiological processes, such as acute or chronic inflammation, autoimmune diseases or tumorigenesis, the role of iNOS activity in most of these diseases is poorly understood. Analysing prostate cancer biopsies by immunohistochemistry we found iNOS protein expression in tumor cells strongly paralleled by nitrotyrosine suggesting that iNOS is fully active. In vitro, NO inhibits androgen receptor-dependent promoter activity and prostate specific antigen production as well as DNA-binding activity of the androgen receptor (AR) in a concentration-dependent manner. Inhibition of the activity of androgen receptor-dependent reporter constructs is neither owing to diminished AR protein levels nor owing to an inhibition of its nuclear import. In addition, NO inhibits the proliferation of androgen receptor-positive prostate cancer cells significantly more efficiently than proliferation of androgen receptor-negative prostate cancer cells. In summary, our findings suggest that intratumoral iNOS activity favors development of prostate cancer cells that are able to proliferate androgen receptor-independently, thereby promoting prostate tumor progression.

[Klippel-Trénaunay syndrome. A rare cause of recurrent macrohematuria: case report]. / Klippel-Trenaunay-Syndrom. Eine seltene Ursache für rezidivierende Makrohämaturie - kasuistische Falldarstellung.

A 37-year-old man with Klippel-Trénaunay syndrome presented with an episode of painless severe gross hematuria. Magnetic resonance imaging (MRI) revealed vessels of significant diameter in the bladder wall. Diagnostic imaging is mandatory in order to be aware of the extent of the lesion as the bleeding identified intraoperatively may only be the "tip of the iceberg." If conservative means fail, laser coagulation should be the treatment of choice.

[Translational research in renal cell cancer. Illustrated by the example of the vascular endothelial growth factor pathway]. / Translation molekularer Zusammenhänge in die klinische Anwendung. Dargestellt am Beispiel des Vascular-Endothelial-Growth-Factor- (VEGF-)Pathway.

For patients with metastatic renal cell cancer (RCC), therapeutic options after cytokine failure are rather limited. There is a considerable need to identify new substances for systemic therapy. Due to upregulation after the loss of a functional von Hippel Lindau gene product, the vascular endothelial growth factor (VEGF) pathway is a promising target for a molecular based therapy. Over the last few years, therapeutic agents have been developed which inhibit this pathway at various levels. Here, we provide an overview of the molecular background and currently used drugs which have entered clinical trials in the setting of metastatic RCC disease. Until now, the results from early clinical trials are very promising, however, the best schedule, dosage, potential combination regimens, as well as long time efficacy, are still to be determined.

[Innovative concepts in early cancer detection and staging of localized prostate cancer]. / Innovative Diagnostik in der Früherkennung und beim Staging des lokalisierten Prostatakarzinoms.

Prostate cancer is the most common malignancy in males. Men aged 50 years and older are recommended to undergo an annual digital rectal examination (DRE) and determination of prostate-specific antigen (PSA) in serum for early detection. Fortunately, disease-specific mortality continues to decline as a result of advances in screening, staging, and patient awareness. However, about 30% of men with a clinically organ-confined disease show evidence of extracapsular extension or seminal vesicle invasion on pathological analysis. Consequently, there is a need for more accurate diagnostic tools for planning tailored treatment. A variety of modern imaging techniques has been implemented in an attempt to obtain more precise staging, thereby allowing for more detailed counseling, and instituting optimum therapy. This review highlights developments in prostate cancer imaging that may improve staging and treatment planning for prostate cancer patients.