Clinical significance of ERG rearrangement subtype and its association with increased p53 expression in Japanese and German prostate cancer.

UNLABELLED: This study investigated differences in prevalence of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) and ETS transcription factor family member, v-ets erythroblastosis virus E26 oncogene homolog (ERG) fusion gene (TMPRSS2-ERG fusions) in clinically localized prostate cancer Japanese and German patients. A total of 105 specimens, including 69 Japanese and 36 German patients, were collected. The status of TMPRSS2-ERG fusion was determined by fluorescence in situ hybridization, and correlations of the TMPRSS2-ERG fusion with clinicopathological characteristics and immunohistochemistry were studied. Gene fusions were identified in 20% (14/69) of Japanese and 53% (19/36) of German patients (P < 0.001). The difference in the type of gene fusion between the two ethnic groups was statistically significant (P=0.024). Overexpression of ERG protein was significantly associated with gene fusion. Biochemical recurrence was significantly higher in patients with ERG overexpression than in those without, and not related to TMPRSS2-ERG fusion status. Interestingly, two types of gene fusions (deletion and increase of copy number) were significantly associated with increased p53 expression (P = 0.005). Association of specific gene fusions harboring higher genomic alterations with p53 expression levels suggests that p53 mutation might drive more aggressive arrangements of TMPRSS2-ERG fusion in prostate cancer. KEYWORDS: ERG, p53, prostate cancer, TMPRSS2-ERG fusion.

[Joint logbook of the GeSRU, DGU, and BDU for "Urological Continuing Education": a milestone for urological continuing education in Germany]. / Das gemeinsame Logbuch "Urologische Weiterbildung" von GeSRU, DGU und BDU : Ein Meilenstein für die urologische Weiterbildung in Deutschland.

Since the new Regulation on Continuing Education took effect, documentation of continuing education is obligatory. At the beginning of 2007, the German Society of Residents in Urology (GeSRU) together with the German Society of Urology (DGU) represented by Professor J. Fichtner initiated a project group with the goal of enhancing the transparency of urological continuing education, modernizing it, and implementing the new possibilities afforded by the new regulation on a nationwide level. Towards realizing this project, which was joined by the Federation of German Urologists (BDU) and the Working Group of Hospital Chiefs of Staff, a joint logbook was designed. In contrast to previously obtainable logbooks, the joint logbook offers, in addition to straightforward documentation of continuing education, a definitive, clear interview guide based on objective data analysis. It provides training in agreeing on sensible objectives, it contains a model curriculum in which continuing education can be systematically yet flexibly structured, and beyond the requirements needed for obtaining qualification as a specialist includes those entitling the physician to bill health insurance providers for urological services rendered as a private practitioner. The joint logbook is accepted as an all-in-one continuing education unit record by the medical associations, health insurance providers, and the European Board of Urology. It takes the form of a dual concept and is available in hard copy as a loose-leaf binder and in a constantly updated online version (http://www.germanresidents-urolog.de).

[The German diagnosis-related groups in urology: reproducibility and quality of coding]. / G-DRG-System für die Urologie : Reproduzierbarkeit und Kodierqualität.

BACKGROUND: The German diagnosis-related group (G-DRG) system is based on the belief that there is only one specific coding for each case. The aim of this study was to compare coding results of identical cases coded by different coding specialists. MATERIAL AND METHODS: Charts of six anonymous cases -- except final letter and coding -- were sent to 20 German departments of urology. They were asked to let their coding specialists do a DRG coding of these cases. The response rate was 90%. RESULTS: Each case was coded in a different way by each coding specialist. The DRG refunding varied by 6-23%. The coding differences were caused by different interpretations of definitions in the DRG system and also by inaccurate chart analysis. CONCLUSION: The present DRG system allows a wide range of interpretation, leading to aggravation of the ongoing disputes between hospitals and insurance companies.

[PSA recurrence following radical prostatectomy and radiotherapy]. / Das PSA-Rezidiv nach radikaler Prostatektomie und Strahlentherapie.

Relapses after curative therapy for localised prostate cancer using radiotherapy or radical prostatectomy occur in a significant percentage of cases, even in times of continually improving patient selection. The definition of a biochemical relapse after surgery is a PSA value of >or=0.4 ng/ml. After radiotherapy with maintenance of the organ and residual PSA production the definition is more complicated. The current algorithm is based on the ASTRO consensus of 1996 and defines a relapse as three consecutive increases in PSA above the post-therapeutic low. A biochemical relapse can indicate a local relapse, systemic metastasising of the disease or a combination of both. The differentiation of these two possibilities can be made, apart from imaging modalities, primarily on the basis of variation in PSA kinetics, whereby a short PSA doubling time and early PSA increase after primary therapy indicate a systemic problem.

[Treatment quality of prostate cancer centers. Analysis of the 2014 annual report of the German Cancer Society]. / Ergebnisqualität aller Prostatakarzinomzentren : Analyse des DKG-Jahresberichts 2014.

BACKGROUND: As of 31 December 2012, 92 departments of urology had been certified as a prostate cancer center by the German Cancer Society (DKG). In this paper, the treatment quality of these centers based on the annual 2014 DKG report shall be critically analyzed. BASIC DATA AND PATIENTS: In 2013, 19,558 primary cases of prostate cancer were registered. The mean number of primary cases per year was 159 (range 101-2089), whereby the minimum number of > 100 had been reached by all centers. The median number of radical prostatectomies decreased to 84 (range 35-2145); 6 of 88 centers did not fulfill the minimum number of 50 radical prostatectomies per year. Concerning radiotherapy or brachytherapy no minimal requirements exist. RESULTS: The number of operative revisions and wound infections including drainage of lymphoceles following radical prostatectomies and the relative number of nerve-sparing radical prostatectomies in low-risk patients with an IIEF > 22 are described. The requirement of < 10 % R1 resections was only fulfilled in 52 of 86 (60.5 %) centers; the median was 8.9 %. Data concerning treatment quality of external beam irradiation as well as data for potency and continence of all treatment modalities are completely lacking. CONCLUSION: The large number of registered prostate cancer cases offers the perfect opportunity to generate reliable benchmark data for all treatment modalities of prostate cancer. It is desirable that in the near future functional data such as continence and potency rates as well as prostate-specific antigen (PSA) recurrences of all treatment modalities will be reported.

[Indicator analysis of prostate cancer centers certified by the German Cancer Society 2015]. / Kennzahlenanalyse der DKG-zertifizierten Prostatakrebszentren des Jahres 2015.

BACKGROUND: Since the first prostate cancer center was certified by the German Cancer Society (DKG) in 2008, there are currently 94 centers at 95 sites. During certification, data on the implementation of the requirements are collected. These data can be used for benchmarking purposes. OBJECTIVES: This paper describes the development and monitoring of indicators and presents a selection of recent results. MATERIALS AND METHODS: The descriptive results on 18,288 primary cases from 91 sites with complete data are presented. RESULTS: The prostate cancer center certification system has reached a plateau both in regard to the absolute number of centers and the total proportion of all primary cases treated in Germany. The implementation of the requirements is at a high level overall, although some centers have difficulties fulfilling selected key figures, e.g., the study quota requirement. CONCLUSION: The evaluation of current indicators documented good structural and process quality, which correspond for the most part to the target values for the total cohort. In the future, assessing medium and long-term outcome quality will be of greater importance, particularly with regard to patient-reported outcomes.

Immunomodulatory and hematopoietic effects of recombinant human interleukin-6 in patients with advanced renal cell cancer.

Interleukin-6 (IL-6) is a cytokine with pleiotropic biologic activities on B cells, T cells, and hematopoietic progenitors. The present study was undertaken to assess pharmacodynamic effects of subcutaneous administration of IL-6 on blood counts, immunologic parameters, and acute-phase reactants. Blood samples were taken from patients with advanced renal cell cancer participating in a phase II trial of recombinant human IL-6. Multiparameter FACS analyses of peripheral blood mononuclear cells were performed using antibodies against CD3, CD4, CD8, HLA-DR, CD56, CD28, CD38, CD19, sIgM, and sIgG. Serum levels of IL-10, soluble CD23 (sCD23), sCD25, IL-1 receptor antagonist protein (IL-1RA), soluble tumor necrosis factor (TNF) receptors (sTNF-R) p55 and p75, and soluble IL-6 receptor (sIL-6R) were detected by ELISA systems. Levels of C-reactive protein (CRP), neopterin, fibrinogen, beta 2-microglobulin, and immunoglobulins M, G, and A were measured by standard methods. In response to administration of IL-6, a significant increment in platelet counts was observed, reaching peak levels after 21 days of treatment. In contrast, leukocyte subsets remained unaffected. No change in number of immunophenotype of peripheral blood B cells, T cells, or natural killer cells could be detected following IL-6 administration. Blood levels of sCD23, IL-10, sIL-6R, neopterin, beta 2-microglobulin, and immunoglobulin subsets were not influenced by cytokine therapy. However, administration of IL-6 led to a slow increment of acute-phase reactants CRP and fibrinogen. Furthermore, the anti-inflammatory molecules sTNF-R p55 and p75 were induced by IL-6, whereas serum levels of IL-1RA remained unchanged. Finally, an increase in blood levels of sCD25 was observed. In conclusion, IL-6 in vivo predominantly acts as a regulator of inflammation and a megakaryocyte differentiation factor.

Primary vesicoureteral reflux in children under one year of age: the case for conservative management?

The natural course of reflux nephropathy was evaluated in children who have been diagnosed for primary vesicoureteral reflux already during the first year of life. The retrospective study in 103 patients (163 refluxive renal units) revealed that 80% of all children in this age group were boys. Scarring at the time of diagnosis was evident in 29% of the cases, compared to a rate of 20% in our whole reflux population. New scarring occurred in 17 patients (18%): 63% of the children had high grade refluxes (IV and V). The rate of spontaneous resolutions was 61% and even grade V refluxes showed a spontaneous cessation in 40% of the cases. These data indicate a high overall spontaneous cure rate in young children, but underline the importance of selecting those patients with already scarred kidneys and recurrent urinary tract infections for an early operation since they are not likely to show a spontaneous resolution of reflux.

[Prognostic parameters of scar progression, new scar formation and maturation in primary vesico-ureteral-renal reflux]. / Prognostische Parameter zu Narbenprogression, neuer Narbenbildung und Maturation beim primären vesiko-uretero-renalen Reflux.

We analysed the data recorded for 901 children (1357 kidneys) treated for primary vesicoureteral reflux between 1973 and 1988 at our institution. The retrospective study showed a rate of 7.3% for new renal scarring and progression; analysis by reflux grade revealed progression and new scarring in reflux, 10.9% of cases with grade IV and 16.5% of cases with grade V whereas low grades (I and II) were followed by no scarring at all. A close correlation of new scarring with urinary tract infection and bladder function was demonstrated. Spontaneous resolution of reflux was observed in 33.6% of all patients and in only 2.6% of patients with grade V reflux, as against a 85.5% resolution rate in patients with grade I or II reflux. A different sex distribution was revealed in the age group under 1 year, in which 80% of the patients were boys and the resolution rate was higher than in any other age group.

[Chromosome abnormalities in hypospadias? An analysis of 131 patients]. / Chromosomenstörungen bei Hypospadien? Eine Analyse bei 131 Patienten.

We performed chromosome studies in 131 patients presenting with hypospadias, with the aim of detecting any causal connections between chromosomal abnormalities and the induction of hypospadias. Autosomal abnormalities were revealed in 6 and sex chromosomal abnormalities in 10 patients. Although a significant causal relationship between the occurrence of hypospadias and chromosomal abnormalities was seen in this study in only two cases of mixed gonadal dysgenesis (45,X/46,XY and streak gonad), the high incidence of chromosomal abnormalities observed (12.2%) seems noteworthy compared with the incidence of only 0.61% in the normal male population.

[Percutaneous embolization of the kidney: indications and clinical results]. / Perkutane Totalembolisation der Niere: Indikationen und klinische Ergebnisse.

OBJECTIVE: Renal embolisation offers a minimal invasive means of renal ablation under primary palliative indication. We evaluated our experience with this technique in a series of 40 patients. PATIENTS AND METHODS: From 1996 to 2002 a total of 40 patients underwent total embolisation of the kidney. Our patients encompassed 15 females and 25-males (median age: 68 years, 46 - 89 years). In 15 patients indication for embolisation was to ablate a non-functioning kidney following obstruction due to advanced cancer, in 9 patients preoperatively with advanced renal cell carcinomas invading the vena cava, in 8 patients for control of hematuria and in 8 patients with non-operable advanced renal cancers. The embolisation was carried out in DAS-technique with a 7 Fr. selective catheter and central placement of macrocoils, from 2000 on we additionally performed a peripheral embolisation with polyvinylalcohol (PVA) particles. The intervention took place in epidural anesthesia. RESULTS: Perioperatively in all patients a complete occlusion of the renal artery as well as acessory arteries (n = 6) could be documented radiographically, perioperative complications were not observed. A post-embolisation syndrome occured in 32 patients. Reinterventions with repeat embolisation became necessary in 5 patients (persistent urine production-n = 4, persistent hematuria-n = 1). SUMMARY: The combined central and peripheral embolisation of the kidney in epidural anesthesia is a valuable means in selected patients under palliative indication for defunctionalisation of the kidney as well as control of hematuria.

Perineal complications following radical perineal prostatectomy.

PURPOSE: Radical perineal prostatectomy has recently attracted renewed interest and wider acceptance as an alternative route to the retropubic approach. While presumed lower morbidity is one reason for perineal prostatectomy we evaluated our patients for complications that are specific for the perineal approach. PATIENTS AND METHODS: We have retrospectively analyzed 412 patients who underwent perineal prostatectomy from 10/1996 to 12/2000. Patients for the perineal approach were selected on the base of preoperative PSA (10 ng/ml) and biopsy Gleason score (< 7) without the need for simultaneous lymphadenectomy. A cystogram was performed routinely on day 7 p. o. and the catheter removed when patent anastomosis was confirmed. Intra-, peri- and postoperative complications were recorded and evaluated. RESULTS: Intraoperative complications encompassed 22 cases of rectal injury (5.5 %) with standard primary 2-layer closure, however 4 patients subsequently developed a stool fistula and 3 required a colostomy. Hematoma in the prostatic fossa was diagnosed in 21 patients (5.2 %) and was removed surgically due to infection or increasing size in 4 patients. In 6.5 % of the patients acute urinary retention occurred after catheter removal (91 % after 7 days), while 4.2 % showed urinary extravasation via the perineal wound. Both incidents healed uneventfully with prolonged catheterization in all except 2 cases with concomitant hematoma in whom open fistula closure with a tunica vaginalis graft was performed. The rate of perioperative transfusion was 6.4 %, transient paresthesia and weakness of the leg were observed in 3 patients. CONCLUSIONS: Radical perineal prostatectomy seems to be a procedure with a low rate of complications and surgical reinterventions. However, the spectrum of observed complications is different to that of retropubic prostatectomy and requires specific management.

[The demographic development in Germany : challenge and chances for urology]. / Die demographische Entwicklung in Deutschland : Herausforderung und Chance für die Urologie.

Urology is affected by the demographic development in Germany more than any other medical discipline. Despite a relatively stable total population, by the year 2040 there will be an absolute and relevant increase in urological diseases caused only by the demographic development in the population. This is particularly true for the increase in oncological treatment just in the field of the discipline of urology. Even now the current numbers for tumor development in Germany (RKI 2014) in the urological oncology segment of all tumor diseases show an increasing trend with more than 23 %. This significant increase in performance is in contrast to the age development of the specialists in this discipline. In total but especially due to the significantly over-aged specialist medical profession in urology, this leads to a substantial bottleneck of specialists in the discipline of urology. This deficiency of personnel resources in urology is aggravated by the requirements of Generation Y for a well-adjusted work-life balance and the associated feminization of the medical profession. This requires intelligent strategies for.

[Secondary malignancies in urinary diversions]. / Sekundärmalignome in Harnableitungen.

In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32 secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and cystoplasty (13-fold) is significantly higher than in other continent forms of urinary diversion such as neobladders or pouches (p<0.0001). The difference between ureterosigmoidostomy and cystoplasty is not significant, nor is the difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%) (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16 tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly at the ureterocolonic borderline in contrast to only 50% following urinary diversions via isolated intestinal segments.From postoperative year 5 regular endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy is necessary at least in the presence of symptoms or should be performed routinely at greater intervals. Following neobladders or conduits, only urethroscopies for urethral recurrence are necessary.

Detecting lymph nodes metastasis in prostate cancer through extended vs. standard laparoscopic pelvic lymphadenectomy.

INTRODUCTION/OBJECTIVE: Pelvic lymphadenectomy is the best method for staging localized prostate cancer. There is no consensus about how the pelvic lymphadenectomy should be performed for patients with cT2, Gleason score 7 or higher, PSA higher than 10 ng/mL. Scintigraphic studies of prostate lymph drainage show that many lymph nodes are not dissected according to the current recommendation of lymphadenectomy which could explain the high rate of cancer recurrence. The objectives of this work are an analysis of the local lymph node metastasis according to the preoperative data (digital examination, PSA and Gleason score) and a comparison between laparoscopic extended and limited pelvic lymphadenectomy, for staging, their technique and complications. METHODS: Two groups were created for analysis. The indications for laparoscopic pelvic lymph-adenectomy are the following: preoperative PSA 10 ng/mL or higher, Gleason score 7 or higher and/or digital examination cT2. Patients with suspected distant metastasis were excluded. The first group is composed of the patients who under-went a limited laparoscopic pelvic lymphadenectomy (LLPL) between January 1995 and December 2002. The medical data were analyzed retrospectively. The second group was created with patients who received extended laparoscopic pelvic lymphadenectomy (ELPL). These data were consecutively collected between November 2006 and October 2007. LLPL was the extraction of the external iliac and obturator lymph nodes. ELPL included, additionally, dissection of the internal iliac lymph nodes as well as tissue medial to the genitofemoral nerve. Histopathological findings were compared with serum PSA, histopathological stage and preoperative biopsy. Complications, operating time, and number of extracted lymph nodes were also compared. RESULTS: There were no significant differences in age, serum PSA or mean biopsy Gleason between two groups. The first group (LPLL) is composed of 381 patients and the second (ELPL), 163. The mean operating time was 72.5 minutes for LLPL and 84.3 for ELPL. The mean number of lymph nodes extracted was 13.8 (LLPL) and 31.1 (ELPL). Metastases were detected in 18.8% (LLPL) and 24.7% (ELPL). In 37.5% of cases, the metastasis occurred in lymph nodes outside from those dissected by LPLL. The rates of complications and conversion rate were not significantly different for the two groups. CONCLUSIONS: For patients with clinically localized prostate cancer, ELPL is associated with a higher rate of detection of lymph node metastasis outside of the field dissected in the LPLL. Pelvic lymphadenectomy, especially extraction of the lymph nodes of the internal iliac is important in patients with preoperative Gleason score 7 or greater and/or serum PSA greater than 10 ng/mL. Laparoscopic lymphadenectomy does not augment the rate of complications and is an excellent technique in prostate cancer staging.