Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: Expression of T-cell co-regulatory proteins has been associated with worse outcomes in patients with UCB. We aimed to confirm these findings. MATERIALS AND METHODS: The study comprised tissue microarrays from 302 consecutive UCB patients treated with RC and lymphadenectomy between 1988 and 2003, 117 matched lymph nodes, and 50 cases of adjacent normal urothelium controls, which were evaluated for B7-H1, B7-H3, and PD-1 protein expression by immunohistochemistry. RESULTS: B7-H3 and PD-1 expression were increased in cancers compared to adjacent normal urothelium (58.6% vs 6% and 65% vs 0%, respectively; both p values < 0.001). Meanwhile, B7-H1 was expressed in 25% of cancers (n = 76). Expression of B7-H3, B7-H1, and PD-1 were highly correlated between the primary tumors and metastatic nodes, with concordance rates of 90%, 86%, and 78% for B7H3, B7H1 and PD-1, respectively. Expression was not associated with clinicopathologic features, disease recurrence, cancer-specific or overall mortality. However, for the subgroup of patients with organ-confined disease (n = 96), B7-H1 expression was associated with an increased risk of overall mortality (p = 0.02) on univariate and trended toward an association on multivariate analyses (p = 0.06). CONCLUSIONS: B7-H1, B7-H3 and PD-1 are altered in a large proportion of UCB. B7-H1 and PD-1 expression are differentially upregulated in cancer versus normal urothelium. High correlation between expression in LN and expression in RC specimens was observed. While expression was not associated with clinicopathologic features or standard outcomes in all patients, B7-H1 expression predicted overall mortality after RC in the subset of patients with organ-confined UCB.

[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.

[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.

[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.

[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.

[Transvesical malposition of a transobturator aortofemoral bypass]. / Transvesikale Fehllage eines transobturatorischen aortofemoralen Bypass.

Besides anatomical bypass procedures, extra-anatomical bypass variations are used for the surgical treatment of peripheral occlusive disease. We report the case of a 64-year-old patient who presented at our clinic with suspected primary bypass malposition.

[Somatostatin analogs for the treatment of advanced, hormone-refractory prostate cancer: a possibility for secondary hormonal ablation?]. / Somatostatin-Analoga in der Therapie des fortgeschrittenen hormonrefraktären Prostatakarzinoms: Eine Möglichkeit der sekundären Hormonablation?

Almost all patients with hormone-refractory prostate cancer under primary androgen deprivation therapy will develop progression, frequently initially marked by an asymptomatic increase of prostate-specific antigen (PSA). Recent data showed that taxane-based chemotherapy offers significant survival benefit to patients with advanced prostate cancer; however, the toxic side effects frequently exert a significant negative impact on the quality of life. At the androgen-independent stage of the cancer, before becoming hormone refractory, progression might still be delayed by secondary manipulation of either androgen or confounding receptors and their signaling pathways. Secondary hormonal manipulations traditionally included antiandrogen withdrawal, second-line antiandrogens, direct adrenal androgen inhibitors, estrogens, and progestins.We discuss the mode of action and application of somatostatin analogs as an emerging secondary hormonal treatment concept in patients with advanced prostate cancer on the basis of the current literature.

[Terminology of lower urinary tract dysfunction and coding in the ICD-10-GM catalogue]. / Terminologie der Blasenfunktionsstörungen und Kodierung im ICD-10-GM-Katalog.

The terminology of lower urinary tract dysfunction was recommended by the AWMF and the German Society of Urology in 2004. However, there is no transfer of this terminology to diagnoses according to the classification of the ICD-10-GM catalogue. This catalogue is of major relevance for remuneration of inpatient and outpatient treatment in the German diagnosis-related groups (DRG) system. This article presents a table showing the correspondence between the current terminology and the ICD-10-GM classification. The correct coding can change the DRG remuneration by a factor of 2 to 3.

[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.

Neobladder emptying failure in males: incidence, etiology and therapeutic options.

PURPOSE: Neobladder reconstruction is considered the best option for patients requiring cystectomy. Limited information is available about incidence, etiology and therapeutic options for neobladder emptying failure in males. MATERIALS AND METHODS: In a retrospective study we analyzed the data of a consecutive series of 655 male patients (age range 23 to 82 years, median 63; followup range 0 to 208 months, median 36.5) who received an ileal neobladder following radical cystectomy at our institution. All patients had a complete followup until death or until December 2003. Data on all diagnostic and therapeutic procedures performed for neobladder emptying failure were collected. RESULTS: Of 655 patients 75 (11.5%) had at least 1 episode of failure emptying the neobladder requiring some form of therapy during followup. Failure was due to dysfunctional voiding in 23 patients (3.5%) and mechanical obstruction in 52 patients (8%). Causes of mechanical obstruction were benign strictures of the neovesicourethral anastomosis (23 patients, 3.5%) or the anterior urethra (11 patients, 1.7%), neoplastic obstruction by local tumor recurrence (13 patients, 2.0%) or a nonurological malignancy (1 patient, 0.2%), and obstruction by mucosal valves (3 patients, 0.5%) or a foreign body (1 patient, 0.2%). In 38 of 52 patients with mechanical obstruction of the neobladder outlet emptying was fully restored with endourological procedures, while in 14 of 52 patients long-term catheterization was necessary. Catheterization was the therapy of choice for all patients with dysfunctional voiding. CONCLUSIONS: Neobladder emptying failure is of major concern but is not an argument against orthotopic diversion. The overall rate of transient or permanent neobladder emptying failure in males is high but most of the mechanical causes can be managed endoscopically, while the rate of patients with long-term catheterization for dysfunctional voiding is relatively low.

[Prospective evaluation of prostate cancer screening in men with a family history of the disease]. / Prospektive Evaluierung der Prostatakarzinomfrüherkennung bei Männern mit familiärer Disposition.

BACKGROUND: Family history is one of the strongest risk factors for prostate cancer. In this prospective study we evaluated the results of prostate cancer screening performed in healthy brothers of prostate cancer patients. The detection rate of prostate cancer and the positive predictive value of the examinations were determined. MATERIAL AND METHODS: The study population comprised 513 healthy men who were 38-75 years of age (median 62.0 years). Of these men, 268 having only one affected brother with prostate cancer were assigned to the sporadic group, and 245 probands having 2-10 affected relatives were assigned to the familial group. An abnormal PSA and/or a pathological digital rectal examination (DRE) was noted in 17.5% of familial (43/245) and 15.8% of sporadic probands (35/268). A biopsy of the prostate was performed in 60.5% of familial (26/43) and 71.4% of sporadic (25/35) men with pathological findings. RESULTS: Prostate cancer was found in 15 of 26 familial (57.7%) and 16 of 25 sporadic (64.0%) probands by prostate biopsy. The overall detection rate was 6.0% (31/513). CONCLUSION: Due to an increased prevalence the detection rate of prostate cancer and the positive predictive value of PSA and/or DRE are higher in men with a family history as expected in an unselected population. Our data suggest that in predisposed men prostate cancer screening should be recommended early. Furthermore an early indication for prostate biopsy is necessary. This recommendation should also be applied if only one first-degree relative has prostate cancer.

[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.

[Application of tissue microarrays for the diagnosis, prognosis and therapeutic decision making in renal cell carcinoma]. / Anwendung von Tissue-Microarrays für die Diagnose, Prognose und Therapieentscheidung beim Nierenzellkarzinom.

The tissue microarray technique (TMA) represents a powerful diagnostic "high-throughput" tool to analyse DNA/RNA or protein alterations in large patient cohorts in a time and cost effective way. This review focuses on the clinical application of TMA in renal cell carcinoma in modern "translational" medicine--"from bench to bedside". In particular, the advantages of TMA for diagnosis, prognosis and decisions for therapy will be considered in relation to renal cell cancer.

[Cytogenetic alterations in renal tumors. Applications for comparative genomic hybridization and fluorescence in situ hybridization]. / Zytogenetische Veränderungen bei Nierentumoren. Einsatzmöglichkeiten von Chromosomen-CGH und Fluoreszenz-in-situ-Hybridisierung.

The WHO classification of renal cell carcinomas (RCC) takes into account chromosomal alterations. New cytogenetic techniques such as comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) offer alternative methods to the classic cytogenetic banding technique. Clear cell (classic) RCC frequently show the loss of 3p. Papillary RCC are characterized by trisomies and tetrasomies as well as loss of the Y chromosome. CGH analysis demonstrates that DNA copy increase is more common in type I papillary RCC compared to type II. Chromophobe RCC are characterized by losses in chromosomes 1, 2, 6, 10, 13, 17, and 21. Oncocytomas can be divided into cases with rearrangements in the 11q13 region and those with loss of chromosome 1 and the sex chromosomes. Translocations involving chromosome 3, such as t(3;8)(p14;q24.13) and t(2;3)(q35;q21) have been described in familial clear cell RCC. The most recent class of RCC, seen only in men, is referred to as translocation tumors. These tumors demonstrate a tubulopapillary growth pattern and have a t(X;1)(p11.2;q21.2) translocation. Although not required for most clinical diagnoses, CGH and FISH complement the standard histologic diagnosis of RCC and may provide a definitive diagnosis in a small number of challenging cases.

[History of high-flow priapism: 1960-2005]. / Geschichte des High-flow-Priapismus: 1960-2005.

High-flow priapism caused by a pathological arterial influx to the cavernous bodies was first described by F.B. Burt in 1960. The pathophysiological differentiation of high- and low-flow priapism was developed in 1983. The development of diagnostic tools for differentiation of different forms of priapism and the progress in the therapy of high-flow priapism from arterial ligation to supraselective embolization is presented.