Trend analysis and regional tumor incidence in Germany for testicular cancer between 2003 and 2014.

BACKGROUND: Testicular germ cell tumor (TGCT) is one the most common solid tumors in men between the age of 15 and 35 with an overall incidence rate of 1-1.5 %. Epidemiologic studies have demonstrated different incidence patterns in western civilized countries with overall rising incidence trends. OBJECTIVE: To analyze differences in regional tumor incidence rates for TGCT and perform a trend analysis for TGCT between 2003 and 2014 in Germany. MATERIAL AND METHODS: TGCT cases in Germany which were diagnosed between 2003 and 2014 were provided by the Robert-Koch-Institute, Berlin. For statistical analysis, cluster and spatial scan tests according to Kulldorff were used for cases with seminoma and non-seminoma. Results are presented in administrative districts and graphically illustrated. We performed a trend-analysis in order to evaluate age-adjusted incidence trends in Germany. Tests were two-sided with a level of significance of α=0.05. RESULTS: In total we included 35,066 patients. Overall, 22,634 cases had newly diagnosed seminoma and 12,432 were diagnosed as non-seminoma. Maximum incidence of seminoma and non-seminoma was observed for age-group 38-40 years and 26-28 years, respectively. No second peak for the incidences of seminoma and non-seminoma with respect to age were observed. Cluster analysis revealed areas with high and low incidence rates as well as slightly different spatial distribution in Germany between seminoma and nonseminoma. Furthermore, there was no significant increase in age-adjusted incidence rates over the reviewed time period in both cohorts. DISCUSSION: In this study differences in reginal tumor incidence rates for seminoma and non-seminoma are reported with both tumor entities revealing distinct clusters. Furthermore, tumor incidence trends for seminoma and nonseminoma between 2003 and 2014 were stable which might indicate the beginning of a plateau phase for TGCT incidence rates in Germany. CONCLUSION: In this analysis we were able to identify regions with significantly higher tumor incidence rates for both seminoma and non-seminoma which were specific for these two subtypes. Furthermore, trend analysis revealed a steady incidence rate for testicular cancer in Germany.

[Urolithiasis 2016 : Reliable, effective and low radiation exposure]. / Steindiagnostik 2016 : Zuverlässig, effektiv und strahlungsarm.

BACKGROUND: Urolithiasis is a widespread disease. Diagnostic imaging plays an important role in the evaluation and management of patients with suspected urolithiasis. Furthermore, modern imaging methods may provide information on stone location, size, fragility and composition aiding the urologist to determine the appropriate treatment modality. PURPOSE: Based on the current literature and guidelines, this review reports on the various new and established diagnostic imaging modalities. RESULTS: Ultrasound should always be the initial imaging modality. Following ultrasound, noncontrast CT-principally using a low-dose protocol-is the imaging modality of choice in the evaluation of patients with acute flank pain and suspected urolithiasis. New imaging modalities like dual energy CT, Uro Dyna CT and digital tomosynthesis are currently under investigation but not yet part of daily clinical practice. Magnetic resonance imaging can be used to detect obstruction caused by urinary stones but is not a first-line imaging modality.

[Patient blood management: Current state of the literature]. / Patient-blood-Management : Stand der aktuellen Literatur.

BACKGROUND: Preoperative anemia has a prevalence of approximately 30% and is one of the strongest predictors of perioperative red blood cell (RBC) transfusion. It is rarely treated although it is an independent risk factor for the occurrence of postoperative complications. Additionally, the high variability in the worldwide usage of RBC transfusions is alarming. Due to these serious deficits in patient care, in 2011 the World Health Organization recommended the implementation of a patient blood management (PBM). OBJECTIVES: This article provides information about PBM as a multidimensional and interdisciplinary approach. MATERIAL AND METHODS: A selective literature search was carried out in the Medline and Cochrane library databases including consideration of national and international guidelines. RESULTS: A PBM promotes the medically and ethically appropriate use of all available resources, techniques and materials in favor of an optimized perioperative patient care. Patients' own resources should be specifically protected, strengthened and used and include (i) diagnosis and therapy of preoperative anemia, (ii) minimizing perioperative blood loss, (iii) blood-conserving surgical techniques, (iv) restriction of diagnostic blood sampling, (v) utilization of individual anemia tolerance, (vi) optimal coagulation and hemotherapy concepts and (vii) guideline-based, rational indications for the use of RBC transfusions. CONCLUSION: A PBM should be advocated as an incentive to evaluate and critically optimize local conditions. An individual, interdisciplinarily structured bundle of different PBM measures has great potential to optimize the quality of patient care and to make it safer.

[Cystectomy in the elderly patient]. / Zystektomie im Alter.

Bladder cancer is a carcinoma of the elderly population. The highest incidence of bladder cancer is between the ages of 70 and 80 years old. Radical cystectomy remains the gold standard for muscle invasive bladder cancer treatment. In this article different aspects of radical cystectomy in elderly patients are reviewed. The Pubmed-MEDLINE database was searched using the following keywords: radical, cystectomy, elderly and age.

Resistance to the mTOR-inhibitor RAD001 elevates integrin α2- and ß1-triggered motility, migration and invasion of prostate cancer cells.

BACKGROUND: Inhibitors of the mammalian target of rapamycin (mTOR) might become a novel tool to treat advanced prostate cancer. However, chronic drug exposure may trigger resistance, limiting the utility of mTOR inhibitors. METHODS: Metastatic potential of PC3 prostate cancer cells, susceptible (PC3(par)) or resistant (PC3(res)) to the mTOR-inhibitor RAD001 was investigated. Adhesion to vascular endothelium or immobilised collagen, fibronectin and laminin was quantified. Motility, migration and invasion were explored by modified Boyden chamber assay. Integrin α and ß subtypes were analysed by flow cytometry, western blotting and real-time PCR. Integrin-related signalling, EGFr, Akt, p70S6kinase and ERK1/2 activation were determined. RESULTS: Adhesion was reduced, whereas motility, migration and invasion were enhanced in PC3(res). The α2 and ß1 integrin subtypes were dramatically elevated, integrins α1 and α6 were lowered, whereas α5 was nearly lost in PC3(res). Activation of the Akt signalling pathway was strongly upregulated in these cells. Treating PC3(par) cells with RAD001 reduced motility, migration and invasion and deactivated Akt signalling. Blocking studies revealed that α2 and ß1 integrins significantly trigger the motile behaviour of the tumour cells. CONCLUSION: Chronic RAD001 treatment caused resistance development characterised by distinct modification of the integrin-expression profile, driving prostate cancer cells towards high motility.

Zoledronic acid influences growth, migration and invasive activity of prostate cancer cells in vitro.

BACKGROUND: The influence of the bisphosphonate zoledronic acid (ZA) on prostate cancer (PC) growth, adhesion and invasive behavior was investigated. METHODS: PC-3, DU-145 and LNCaP cells were treated with ZA, and tumor-cell growth was then investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Furthermore, tumor-cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins, as well as migratory properties of the cells, was evaluated. Integrin ß subtypes, integrin-dependent signaling, as well as cell-cycle regulating proteins, were analyzed by western blots. RESULTS: ZA dose-dependently reduced tumor-cell growth but did not impair tumor-endothelium and tumor-matrix interaction. However, ZA significantly inhibited tumor migration and invasive activity. Cyclin E was reduced by ZA in LNCaP and DU-145, and p21 was elevated in LNCaP cells. p27 was upregulated in all tumor cell lines, compared with the controls. ZA elevated ß1-integrin in PC-3 and diminished ß4-integrin in PC-3 and DU-145 cells. CONCLUSIONS: ZA inhibits PC growth and motility but does not influence the mechanical contact between tumor cells and the vascular wall.

Upgrading of Gleason score 6 prostate cancers on biopsy after prostatectomy in the low and intermediate tPSA range.

When offering watchful waiting or active monitoring protocols to prostate cancer (PCa) patients, differentiation between Gleason scores (GS) 6 and 7 at biopsy is important. However, upgrading after prostatectomy is common. We investigated the impact of different PSA levels on misclassification in the PSA range of 2-3.9 and 4-10 ng ml(-1). A total of 448 patients with GS 6 PCa on prostate biopsy were evaluated by comparing biopsy and prostatectomy GS. Possible over diagnosis was defined as GS <7, pathological stage pT2a and negative surgical margins, and possible under diagnosis was defined as pT3a or greater, or positive surgical margins; the percentage of over- or under diagnosis was determined for correctly and upgraded tumors after prostatectomy. A match between biopsy and prostatectomy GS was found in 210 patients (46.9%). Patients in the PSA range of 2.0-3.9 and 4.0-10.0 ng ml(-1) were upgraded in 32.6 and 44.0%, respectively. Over diagnosis was more common than under diagnosis (23.2% vs 15.6%). When upgraded there was a significant increase in under diagnosis. As almost 40% of GS 6 tumors on biopsy are GS 7 or higher after surgery with a significant rise in under diagnosis there is a risk of misclassification and subsequent delayed or even insufficient treatment, when relying on favorable biopsy GS.

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.

Health-related quality of life in children with vesicoureteral reflux - impact of successful endoscopic therapy.

OBJECTIVES: Endoscopic therapy for vesicoureteral reflux (VUR) using dextranomer/hyaluronic acid (Dx/HA) has become increasingly popular, but the subjective impact of this therapy and subsequent reflux resolution on health-related quality of life (HRQoL) remains unclear. The aim of this study was to address this issue. MATERIALS AND METHODS: One hundred children (65 girls, 35 boys; mean age 4.46 years) cured of primary VUR by endoscopic treatment were retrospectively reviewed. The Glasgow children's benefit inventory (GCBI) - a validated, reproducible, post-interventional questionnaire consisting of four subscales - supplemented by sociodemographic and disease-specific questions was employed. The HRQoL benefit was calculated on a scale ranging from -100 (complete failure) to +100 (complete success) and correlated with supplementary data. RESULTS: Total response rate was 88%. Mean total GCBI score was 28.4+/-20.3 representing a significant HRQoL amelioration. All GCBI subscores improved with the physical health subscale being most relevant. A gender-specific, significant difference in relative GCBI scores was discovered. Correlation with critical life events and time since operation proved the positive effect on HRQoL to be durable. CONCLUSIONS: Resolution of primary VUR secondary to Dx/HA treatment significantly improves HRQoL. HRQoL is positively affected in many areas and not only in those directly associated with VUR. These improvements are not temporary, suggesting that successful Dx/HA therapy may be superior to medical management in terms of children's quality of life.

Extracellular microenvironment and cytokine profile of the ureterovesical junction in children with vesicoureteral reflux.

PURPOSE: Vesicoureteral reflux is caused by a defective valve mechanism of the ureterovesical junction. Previous studies have revealed structural and metabolic changes in the intravesical ureter, impairing its contractile properties. Smooth musculature and nerves are replaced by collagen, while matrix degrading enzymes are over expressed. We investigated the presence of regulating cytokines and the extracellular matrix composition to elucidate further the pathophysiology of vesicoureteral reflux. MATERIALS AND METHODS: Ureteral endings were obtained from 28 children during antireflux surgery, and 14 age matched autopsy specimens served as controls. Routine histological sections were immunostained for insulin-like growth factor-1, nerve growth factor, transforming growth factor-beta1, tumor necrosis factor-alpha and vascular endothelial growth factor. Smooth muscle staining was supplemented by tenascin C, tetranectin and fibronectin detection. Staining patterns were investigated using computer assisted, high power field magnification analyses. RESULTS: Tumor necrosis factor-alpha and transforming growth factor-beta1 were significantly more abundant in vesicoureteral reflux samples, whereas insulin-like growth factor-1, nerve growth factor and vascular endothelial growth factor were more prevalent in healthy controls. Fibronectin was intensely expressed in refluxing ureters, while it was scarce in healthy children. Tenascin C was notable within the urothelium of both groups. Only vesicoureteral reflux samples displayed tenascin C in the musculature and connective tissue. Tetranectin staining was only detected in vesicoureteral reflux. CONCLUSIONS: Several cytokines are differentially expressed in primary refluxing ureters, indicating an ongoing tissue remodeling process in the ureterovesical junction region. Additionally, the smooth muscle coat is widely lacking, while extracellular matrix proteins typical for tissue shrinkage and reorganization are over expressed. These alterations are likely to contribute to the malfunctioning active ureteral valve mechanism in primary vesicoureteral reflux.

5-alpha-reductase and the development of the human prostate.

During the 10(th) week of gestation human prostate development is about to start. Androgens are the crucial factors to stimulate the initial interactions between the epithelium and mesenchyme. One of the key events in androgen metabolism is the transformation of circulating testosterone to 5alpha-dihydrotestosterone (DHT) by tissue-linked 5alpha-reductase. Both, the formation of a male phenotype and the androgen-mediated growth of the prostate are mediated by DHT. To date the function of 5alpha-reductase 1 (5alphaR1) still remains unclear whereas 5alpha-reductase 2 (5alphaR2) is supposed to be the predominant isoenzyme in human accessory sex tissue. Only little data are available on the detection, distribution, and effects of both isoenzymes during fetal life and infancy. Recently, immunohistochemical investigations of serial sections from fetuses and infants using specific antibodies directed against 5alphaR1 and 5alphaR2 seem to shed light on that issue. Moreover, the detection of downstream products of androgen synthesis using RT-PCR analyses for 17-beta hydroxysteroid dehydrogenase Type 2 (17 betaHSD 2), 17 betaHSD Type 3 and 17 betaHSD Type 7 adds to discovering the molecular biological background. New studies confirm that both isoenzymes are present throughout fetal development. On the transcriptional level RT-PCR for 5alphaR1 and 5alphaR2 certifies these findings. 17 betaHSD 2, 3 and 7 representing the most relevant enzymatic downstream products of cellular androgen synthesis were revealed by RT-PCR as well. Current studies discovered the expression and distribution of both 5alpha-reductase isoenzymes as well as the potential contribution of 5alphaR1 during fetal human prostate development.

The efficacy of dihydrotestosterone transdermal gel before primary hypospadias surgery: a prospective, controlled, randomized study.

PURPOSE: We sought to evaluate the efficacy of transdermal dihydrotestosterone treatment based on the results of hypospadias repair in children with primary hypospadias. MATERIALS AND METHODS: A total of 75 randomized consecutive children who were a mean of 33.4 +/- 3.7 months old and had primary hypospadias were included in the study between September 2004 and April 2006. While 37 children were treated with 2.5% transdermal gel daily, applied directly onto the penile shaft and glans for 3 months (group 1), 38 children did not receive any treatment preoperatively (group 2). All children underwent hypospadias repair using tubularized incised plate urethroplasty. Postoperative complications were analyzed using the Mann-Whitney U test with respect to fistulas, urethral strictures, diverticula, meatal stenosis, glanular dehiscence and scar formation according to the results at 1-year followup. RESULTS: Mean ages of the children in groups 1 and 2 were similar (30.8 +/- 5.4 months and 35.1 +/- 5.1 months, respectively). The urethral meatus was coronal in 70%, penile in 24% and penoscrotal in 5% of the patients in group 1, while it was coronal in 84% and penile in 16% of the patients in group 2. Postoperative complications included urethrocutaneous fistula in 4 patients (11%) in group 2, compared to 1 patient (3%) in group 1 (p >0.05). While 3 patients (8%) in group 2 had glanular dehiscence, no patient in the dihydrotestosterone group had this complication (p <0.05). There were 2 patients with meatal stenosis in group 2 (5%), and no patient with meatal stenosis in group 1 (p >0.05). In addition, there were 16 patients (42%) with moderate to severe postoperative scar formation in group 2, compared to only 2 patients (5%) in the dihydrotestosterone group (p <0.05). Finally, there was a significant difference between the overall reoperation rates of group 2 (9 patients, 24%) and group 1 (1 patient, 3%, p <0.05). None of our patients had signs or symptoms of urethral stricture or urethral diverticulum. CONCLUSIONS: Pretreatment with dihydrotestosterone transdermal gel was effective in decreasing the complications and improving the cosmetic results after hypospadias repair.

Sonographic measurement of renal pelvis wall thickness as diagnostic criterion for acute pyelonephritis in adults.

PURPOSE: Inflammatory processes may increase the urothelial thickness of the renal pyelon. Purpose of the study was to assess sonographic measurement of pyelon wall thickness (PWT) in adult patients with acute pyelonephritis, chronic urinary tract infection (UTI) and indwelling ureteral stents. MATERIALS AND METHODS: Four study groups (acute pyelonephritis n=50, chronic UTI n=10, indwelling ureteral stents n=10, controls n=25) underwent renal ultrasonography (Acuson Seqouia, Mountain View, CA; 6 MHz Transducer). The renal pyelon was imaged in transverse and longitudinal planes. PWT measurements of patients with acute pyelonephritis were repeated after successful antibiotic treatment. RESULTS: Mean PWT in healthy controls was 1.0 mm+/-0.19. In patients with acute pyelonephritis, PWT was significantly increased to 2.9 mm+/-0.89 (p<0.001). PWT decreased significantly after antibiotic treatment to 1.4 mm+/-0.47 (p<0.001). Kidneys with indwelling stents presented with a PWT of 2.7 mm+/-0.68, kidneys with chronic UTI demonstrated a PWT of 2.8 mm+/-0.62. PWT in these patient groups was significantly greater than PWT in healthy volunteers (p<0.001). The interobserver agreement was excellent (p<0.001). CONCLUSION: PWT is a reproducible diagnostic criterion for acute pyelonephritis. Based upon our experience, we suggest a cut-off value of 2.0 mm to distinguish healthy kidneys from those with urothelium thickened by inflammation. PWT cannot be used to distinguish acute pyelonephritis from chronic inflammation of the urothelium.

Transurethral ultrasonography-guided injection of adult autologous stem cells versus transurethral endoscopic injection of collagen in treatment of urinary incontinence.

In the last years preclinical studies have paved the way for the use of adult muscle derived stem cells for reconstruction of the lower urinary tract. Between September 2002 and October 2004, 42 women and 21 men suffering from urinary stress incontinence (age 36-84 years) were recruited and subsequently treated with transurethral ultrasonography-guided injections of autologous myoblasts and fibroblasts obtained from skeletal muscle biopsies. The fibroblasts were injected into the urethral submucosa, while the myoblasts were implanted into the rhabdosphincter. In parallel, 7 men and 21 women (age 39-83 years) also diagnosed with urinary stress incontinence were treated with standard transurethral endoscopic injections of collagen. Patients were randomly assigned to both groups. After a follow-up of 12 months incontinence was cured in 39 women and 11 men after injection of autologous myoblasts and fibroblasts. Mean quality of life score (51.38 preoperatively, 104.06 postoperatively), thickness of urethra and rhabdosphincter (2.103 mm preoperatively, 3.303 mm postoperatively) as well as contractility of the rhabdosphincter (0.56 mm preoperatively, 1.462 mm postoperatively) were improved postoperatively. Only in two patients treated with injections of collagen incontinence was cured. The present clinical results demonstrate that, in contrast to injections of collagen, urinary incontinence can be treated effectively with ultrasonography-guided injections of autologous myo- and fibroblasts.

Comparison of contrast enhanced color Doppler targeted biopsy to conventional systematic biopsy: impact on Gleason score.

PURPOSE: Prostate cancer grading with Gleason score is an important prognostic factor. This prospective randomized study compares ultrasound systematic biopsy vs contrast enhanced color Doppler targeted biopsy for the impact on Gleason score findings. MATERIALS AND METHODS: We examined 690 men (mean age 56 years, range 41 to 77) with a serum total prostate specific antigen of 1.25 ng/ml or greater, a free-to-total prostate specific antigen ratio less than 18% and/or a suspicious digital rectal examination. Contrast enhanced color Doppler targeted biopsies with a limited number of cores (5 or less) were performed in hypervascular areas of the peripheral zone during administration of the ultrasound contrast agent Sonovuetrade mark (Bracco, Milano, Italy). Ten systematic biopsies were obtained in a standard spatial distribution. Cancer detection rates and Gleason score were compared. RESULTS: Prostate cancer was identified in 221 of 690 subjects (32%) with a mean prostate specific antigen of 4.6 ng/ml (range 1.4 to 35.0). Prostate cancer was detected in 180 of 690 subjects (26%) with contrast enhanced color Doppler targeted biopsy and in 166 of 690 patients (24%) with systematic ultrasound biopsy. The Gleason score of all 180 cancers detected on contrast enhanced color Doppler targeted biopsy was 6 or higher (mean 6.8). The Gleason score of all 166 cancers detected on systematic biopsy ranged from 4 to 6 and mean Gleason score was 5.4. Contrast enhanced color Doppler targeted biopsy detected significantly higher Gleason scores compared to systematic biopsy (Wilcoxon rank sum test p <0.003). CONCLUSIONS: Contrast enhanced color Doppler targeted biopsy detected cancers with higher Gleason scores and more cancer than systematic biopsy. Therefore, contrast enhanced color Doppler seems to be helpful in the grading of prostate cancer, which is important for defining prognosis and deciding treatment.