Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

Does trunk muscle training with an oscillating rod improve urinary incontinence after radical prostatectomy? A prospective randomized controlled trial.

OBJECTIVE: To investigate the effect of a new therapeutic approach, using an oscillating rod to strength the pelvic floor and deep abdominal musculature and to speed up recovery of continence after radical prostatectomy. DESIGN: Prospective randomized controlled clinical trial. SETTING: Inpatient uro-oncology rehabilitation clinic. SUBJECTS: Ninety-three (intervention group (IG)) and ninety-one patients (control group (CG)) with urinary incontinence after prostatectomy were examined. INTERVENTION: All patients were randomly allocated to either standard pelvic floor muscle exercises and oscillating rod therapy (IG) or standard pelvic floor muscle exercises and relaxation therapy (CG). MAIN OUTCOME MEASURES: Urinary incontinence (1- and 24-hour pad test) was assessed, and health-related quality of life (HRQL; Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire) was measured for all patients before and after three weeks of treatment. RESULTS: One hundred and eighty-four patients (mean (SD) age: 64.1 (6.94) years) completed the study. The IG showed a significant reduction in urinary incontinence (1-hour pad test: P = 0.008, 24-hour pad test: P = 0.012) and a significant improvement of HRQL (P = 0.017) compared with CG. Continence was significantly improved in both groups (1-hour pad test: 22.6-8.5 g (IG) vs. 23.0-18.1 g (CG)/24-hour pad test: 242.9-126.7 g (IG) vs. 237.6-180.9 g (CG)). CONCLUSION: The study demonstrated that a combination of conventional continence exercises and the new oscillation rod training increased abdominal and pelvic floor musculature and speeded up recovery of continence after radical prostatectomy.

Cancer treatment regimens and their impact on the patient-reported outcome measures health-related quality of life and perceived cognitive function.

BACKGROUND AND PURPOSE: Breast cancer can be a significant challenge for those affected. Knowledge of physical function, social-emotional challenges, and perceived cognitive function based on the cancer treatment regimens may help to inform adequate support. METHODS: For this prospective observational pilot study, we collected data of seventy-nine women (mean age 54.6 ± 9.5 years) before (T0) and after (T1) initial breast cancer treatment. Functional Assessment of Cancer Therapy-Breast (FACT-B) and Functional Assessment of Cancer Therapy-Cognitive-Function (FACT-Cog) were used to collect data of four treatment subgroups: SCR = Surgery + Chemotherapy + Radiation Therapy; SC = Surgery + Chemotherapy; SR = Surgery + Radiation Therapy; S = Surgery. A mixed ANOVA and posthoc analysis (Tukey, Games-Howell) were used to detect interactions (group by time) and the main effect. A repeated-measures ANOVA displayed individual group differences (time). RESULTS: Significant interaction showed more deterioration was experienced with SC and SCR than SR and S for FACT-B (p < 0.01) and FACT-Cog (p < 0.001). The longitudinal comparison between T0 and T1 indicated a significant group main effect on all subscales (p < 0.001) except for Emotional Well-Being. Significant reductions (p < 0.05) in FACT-B, (- 19%); FACT-Cog, (- 21%) with most pronounced effect in Physical Well-Being (- 30%), Functional Well-Being (- 20%), Breast Cancer Subscale (- 20%), Perceived Cognitive Impairments (- 18%) and Impact of Cognitive Impairments on Quality of Life (- 39%) were detected for SCR. CONCLUSION: Our study showed that the extent of change in health-related quality of life (HRQoL) and perceived cognitive function (PCF) depends on the treatment regimen. Multidisciplinary support initiated early in breast cancer therapy is needed, especially for women undergoing combined cancer treatment. Routine assessment of patient-reported outcomes (PROs) in oncology practice may increase the transparency of patients' perceived circumstances, leading to personalized and optimized acute and survivorship care.

[Rehabilitation of patients with interstitial cystitis/bladder pain syndrome (IC/BPS)]. / Rehabilitation von Patienten mit Interstitieller Cystitis/Bladder Pain Syndrom (IC/BPS).

After unsuccessful outpatient conservative treatment or invasive inpatient treatment and after cystectomy in interstitial cystitis/bladder pain syndrome (IC/BPS), an inpatient discipline-specific urological rehabilitation (rehab) should be proposed according to the German guideline on IC/BPS. During rehab, diagnostic results will be completed. Multimodal therapy includes the optimisation of lifestyle and medication. Intensive psychotherapy may frequently improve the processing of the disease. Various forms of exercise therapy and physical therapy with water applications, thermotherapy, several forms of massage and electrical or magnetic therapies as well as nutritional advice frequently alleviate complaints in IC/BPS. The different therapies are modified during rehab, if necessary. Social medicine evaluation and advice, e.g. on grade of handicap or ability to work, are also important issues in rehab. Two-thirds of patients show an essential improvement after rehab, which lasts for a prolonged period in about 50% of patients.

Bioelectrical Impedance Vector Pattern and Biomarkers of Physical Functioning of Prostate Cancer Survivors in Rehabilitation.

BACKGROUND: Knowledge of clinically established factors of physical function such as body composition, bioelectrical phase angle (PhA) and handgrip strength (HGS) with mortality predictive and health-related relevance is limited in prostate cancer survivors (PCS). Therefore, the aim of this study was to characterise and compare body composition data of PCS with extensive reference data as well as to analyse PhA and HGS and the prevalence of critical prognostic values at an early stage of cancer survivorship. METHODS: One hundred and forty-eight PCS were examined at the start (T1) and end (T2) of a 3-week hospitalised urooncological rehabilitation, which began median 28 days after acute cancer therapy. Examinations included a bioimpedance analysis and HGS test. Comparison of body composition between PCS and reference data was performed using bioimpedance vector analysis (BIVA). RESULTS: BIVA of the whole PCS group showed abnormal physiology with a cachectic state and a state of overhydration/oedema, without significant changes between T1 and T2. The age- and BMI-stratified subgroup analysis showed that PCS aged 60 years and older had this abnormal pattern compared to the reference population. HGS (T1: 38.7 ± 8.9 vs T2: 40.8 ± 9.4, kg), but not PhA (T1/T2: 5.2 ± 0.7, °), changed significantly between T1 and T2. Values below a critical threshold reflecting a potentially higher risk of mortality and impaired function were found for PhA in 20% (T1) and 22% (T2) of PCS and in 41% (T1) and 29% (T2) for HGS. CONCLUSIONS: BIVA pattern and the prevalence of critically low HGS and PhA values illustrate the necessity for intensive continuation of rehabilitation and survivorship care especially in these 'at risk' cases. The routine assessment of body composition, PhA and HGS offer the opportunity to conduct a risk stratification for PCS and could help personalising and optimising treatment in rehabilitation and ongoing survivorship care.

Is there a relationship between chronic bladder dysfunction and somatic symptoms in other body regions? 1. Clinical observations.

OBJECTIVE: Investigation of patients with chronic bladder dysfunction regarding associated general symptoms and complaints in the cervico-facial, upper and lower extremity regions. PATIENTS AND METHODS: We retrospectively evaluated history, physical and special neurourological examination and urodynamic studies in 213 patients with non-neurogenic bladder dysfunction. RESULTS: 22 patients out of 213 patients with chronic bladder dysfunction reported reproducible associated symptoms involving the temporo-mandibular joint, the distal forearm/hand or feet and headache. There was an obvious clinical connection regarding the severity of bladder dysfunction and associated symptoms and possible relief of both by successful treatment. CONCLUSION: Symptomatic lower urinary tract dysfunction may accompanied by specific muscular and or sensory disturbances in different areas of the body. These associated pathologies in patients without neurological disease can be explained by functional changes in a complex autonomic peripheral and central nervous network.

Is there a relationship between chronic bladder dysfunction and somatic symptoms in other body regions? 2. An experimental neuroanatomical approach.

OBJECTIVE: Based on clinical description of associated dysfunctional symptoms in patients with non-neurogenic lower urinary tract dysfunction an experimental setup was created in order to investigate the neuroanatomical basis for the clinical phenomena observed. METHODS: Using 24 male adult Sprague-Dawley rats for retrograde mapping of the spinal cord and brain, a pseudorabies virus (PRV) tracer was subsequently injected into four pertinent locations; (a) the trigone, (b) the masseter muscle (c) the forepaw and (d) the hindpaw. RESULTS: PRV tracing demonstrated clearly overlapping of labeled areas in the brain stem, diencephalon and thoracic-lumbar cord, from all injection sites of the rats. CONCLUSION: There is a diffuse overlap within the brain stem and spinal cord, of autonomic innervation to peripheral tissues based on the presented animal experiments. The described autonomic network allows an understanding of the occurrence of symptoms in distant regions of the body associated to chronic bladder dysfunction.

Spinal NK1 receptor is upregulated after chronic bladder irritation.

It has been suggested that there is a significant upregulation of the NK1 receptor (NK1R) on neurons in the dorsal spinal cord after long-term somatic inflammation. This upregulation appears to play a significant role in central sensitization in chronic pain states. However, it is not clear whether such a change is also observed after chronic visceral (bladder) inflammation. Changes in NK1R immunoreactivity after chronic bladder irritation were investigated in order to evaluate the existence of hypersensitive states in the spinal cord after chronic bladder irritation. Experiments were performed on a total of 12 adult female Sprague-Dawley rats. In six animals, cyclophosphamide (CPA) was administered intraperitoneally for 2 weeks. Another six animals were given intraperitoneal saline injections and served as the control group. After these treatments, immunohistochemical staining for NK1Rs and substance P in rat lumbosacral spinal cord was performed. In CPA-treated animals, NK1R-positive areas and staining intensity within the dorsal spinal cord were significantly increased in the L5 to S2 spinal cord areas, especially in the L6 and S1 segments. In the L6 spinal segment, CPA-treatment enhanced NK1R immunostaining in the medial and the lateral dorsal horn, as well as in the lateral laminae including the sacral parasympathetic nucleus to a lesser extent. In CPA-treated animals, substance P staining intensity increased in the same regions in which NK1R immunoreactivity was increased. This finding probably implies the upregulation of spinal NK1R and the occurrence of central sensitization within the spinal cord after chronic visceral inflammation.

Bladder dysfunction and end stage renal disease.

INTRODUCTION AND OBJECTIVES: Evaluation of lower urinary tract function in patients with end-stage renal disease and lower urinary tract symptoms. Patients were screened before entering a renal transplantation program. MATERIALS AND METHODS: A diagnostic work-up including urodynamics was performed on 52 patients (14 women, 38 men) suffering from renal failure due to chronic glomerulonephritis (n = 25), diabetic nephropathy (n = 15), chronic pyelonephritis/stone disease (n = 9) and polycystic kidney disease (n = 3). RESULTS: Abnormalities in lower urinary tract function of different degrees were found in 40 patients (77%). Major problems are bladder hypersensitivity (n = 31%), poor bladder compliance (38%), detrusor instability (25%) and detrusor-sphincter dyssynergia (33%). CONCLUSIONS: There is a high incidence of bladder dysfunction of different degrees in patients with renal failure. The clinical significance, especially in the long term, needs to be evaluated. However, a urodynamic assessment before renal transplantation is recommended in all patients reporting symptoms of dysfunctional voiding and/or bladder storage problems in order to avoid allograft dysfunction due to chronic bladder dysfunction and related complications. Depending on the degree of bladder dysfunction an urodynamic follow-up after transplantation is necessary. If there are no symptoms and no history of lower urinary tract dysfunction an urodynamic assessment is not necessary.

Efferent control of different visceral pelvic organs by spinal and supraspinal centres.

A growing number of patients with pelvic organ dysfunction and failing response to standard treatment concepts are referred to special neuro-urology services. New therapeutic options are available, such as unilateral and bilateral sacral nerve stimulation, and the use of different neurotoxins for the overactive bladder. However, a lack of knowledge and understanding in central innervation and modulation of pelvic organ function prevents a striking progress in this clinical area. A concept of efferent innervation of pelvic organs based on experimental animal studies, using the retrograde, transneuronal and self-amplifying tracer Pseudorabiesvirus, is discussed in a clinical context.

[Demand for and clinical practice of complementary selenium therapy in prostate cancer patients]. / Bedarf und Praxis der gezielten Selensubstitution im Rahmen der komplementären Behandlung des Prostatakarzinoms.

BACKGROUND: Selenium supplementation is a popular and broadly adopted complementary oncological treatment option. The aim of the study was the evaluation of the necessity and the indication for selenium therapy in prostate cancer patients. METHODS: 295 consecutive patients after radical prostatectomy were evaluated for oncological, basic laboratory and lifestyle characteristics. The selenium level was measured using graphite furnace atom absorption spectroscopy. RESULTS: The median selenium level was 103.4 (72.9­142.1) µg/l. Correlations were found between a low selenium level and progressed cancer disease, positive lymph node status, chronic nicotine and alcohol abuse, and chronic multiple medications. CONCLUSION: Based on a documented low selenium level in 96.3% of investigated prostate cancer patients and the known consequences of an insufficient selenium supply, a targeted selenium supplementation is recommended. Selenium therapy should be part of an individual medical nutritional and lifestyle intervention.

Comparison of three staining methods for the morphological evaluation of human spermatozoa.

OBJECTIVE: To compare different staining methods to evaluate human sperm morphology. DESIGN: Prospective study. SETTING: Patients at the Departments of Dermatology and Urology, University of Jena, Germany. PATIENT(S): A total of 94 randomly collected patients attending the andrological outpatient clinics of the Departments of Dermatology and Urology, University of Jena, Germany. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Statistical comparison of resultant standard morphological parameters (mean percentages) after staining according to Papanicolaou and Shorr methods and with Testsimplets prestained slides. RESULT(S): All morphological parameters investigated (percent normal morphology, percent head, midpiece, and flagellar abnormalities) correlated statistically significantly positively, however with markedly lower correlation coefficients for the Testsimplets results. As compared with the mean Papanicolaou (4.78% +/- 2.54%) and Shorr staining (4.75% +/- 2.64%) results, a statistically significantly lower percentage of morphologically normal spermatozoa was determined after using the Testsimplets slides (3.89% +/- 2.53%). In general, the mean values of all parameters differed for all comparisons with the Testsimplets slides and especially for the percentage of flagellar defects but not between the Papanicolaou and the Shorr staining results. CONCLUSION(S): The results show an extensive agreement between the Papanicolaou- and Shorr-stained smears, whereas Testsimplets staining exhibited statistically significant deviations. Because the correct evaluation of sperm morphology is of essence within the scope of assisted reproduction and in andrological diagnostics, the use of rapid staining methods cannot be recommended.

Frequency and nocturia after successful renal transplantation: a normal situation?

OBJECTIVE: To analyse lower urinary tract function before and after successful renal transplantation and compare the data with those from a healthy control group. PATIENTS AND METHODS: Data were gathered by retrospective analysis of 331 charts of patients transplanted between March 1998 and May 2003, using written questionnaires and personal interview, and investigation of 150 patients. The control group consisted of 150 urologically healthy volunteers. RESULTS: Frequency and nocturia were the main lower urinary tract symptoms. Frequency of more than six voids/day was reported by 87% and nocturia of more then one void/night by 93% of all patients after successful renal transplantation. There was no significant correlation with fluid intake, diuretic medication, gender or age. Over the years the number of voids tended to decrease but remained higher than in the control group. However, 94% of all patients were happy with the quality of life after renal transplantation. CONCLUSION: Frequency and nocturia are the two main characteristics of lower urinary tract function after renal transplantation, probably through a combination of high fluid intake, a long-term defunctionalized urinary bladder during renal replacement therapy, a denervated donor kidney, concomitant diseases and psychosocial distress. Quality of and satisfaction with life were not compromised.

Penile prosthetic surgery in neurologically impaired patients: long-term followup.

PURPOSE: Penile prosthetics are a viable option for erectile dysfunction in neurologically impaired patients. Penile implants can also be used to facilitate the management of urinary drainage when penile retraction has made this difficult. MATERIALS AND METHODS: Between 1980 and 1996, 245 neurologically impaired patients with a mean age of 40.8 years (range 16 to 75), including 188 with paraplegia, 57 with quadriplegia and 197 with spinal cord injuries, were treated for erectile dysfunction and/or urinary incontinence with penile prosthesis implantation. The mean history of paralysis was 11.2 years (range 1 to 52). After neuro-urological evaluation all patients included in this study were considered candidates for penile prosthesis implantation. A followup program for treatment success, patient satisfaction, problems and complications was subsequently initiated. RESULTS: During 17 years a total of 293 surgical procedures in 245 patients were done with the implantation of 147 semirigid (Jonas), 113 self-contained inflatable (Dynaflex) and 33 inflatable 3-piece (AMS 700) prostheses. There were 3 patient groups based on the indication for penile prosthetic surgery, namely group 1-134 patients with urinary management only, group 2-60 with erectile dysfunction only, and group 3-51 with urinary management and erectile dysfunction. At a mean followup of 7.2 years (maximum 17) 195 patients were reevaluated in clinic. In 122 patients (90.3%) urinary management problems were resolved. Erectile dysfunction treatment was successful in 76 patients (82.6%). There were 43 revisions for technical reasons and infections. The infection rate was 5% (12 patients). The perforation rate was different for different implant devices, that is 18.1% (15 of 83 cases) for semirigid devices, 2.4% (2 of 84) for self-contained inflatable devices and 0% (0 of 28) for inflatable 3-piece devices. CONCLUSIONS: The implantation of a penile prosthesis is a safe procedure for erectile dysfunction and/or urinary incontinence in neurologically impaired patients. Based on technical advances the complication rates significantly decreased during the years. The implantation of an inflatable 3-piece penile prosthesis in a neurologically impaired patient is a safe and viable procedure. Indications include the management of erectile dysfunction and problematic urinary collection.

Central autonomic innervation of the kidney. What can we learn from a transneuronal tracing study in an animal model?

PURPOSE: Renal sympathetic innervation is involved in the maintenance of fluid homeostasis, modulation of renal secretion from juxtaglomerular cells, sodium resorption from renal tubular cells and renal hemodynamics. The understanding of central innervation and neuronal connections is important for studying the consequences of renal disease and surgical interventions compromising renal nerves. MATERIALS AND METHODS: A total of 38 individual adult male Sprague-Dawley rats were used for retrograde transneuronal mapping of the spinal cord and brain stem after pseudorabies virus (PRV) injection into the left kidney in 30 and control experiments in 8. After a survival time of 72, 96 or 120 hours the animals were sacrificed. Exploration of the abdominal and pelvic visceral organs was done, and the brain and spinal cord were harvested via dorsal laminectomy. After cutting on a freezing microtome the tissue was immunostained for PRV. RESULTS: After kidney injection inspection of the abdominal and pelvic cavity revealed an enlarged bladder with hemic urine. The urine was sterile and the bladder wall showed signs of neurogenic inflammation. Other organs were not affected. PRV positive cells were primarily found within the ipsilateral nucleus intermediolateralis of thoracic spinal cord segments T6 to T13. At the supraspinal level PRV positive cells were found within certain regions, namely the nuclei raphes, rostral ventromedial and ventrolateral medulla, A5 noradrenergic cell region, locus coeruleus and nucleus paraventricularis of the hypothalamus. CONCLUSIONS: This investigation demonstrates the anatomical basis for broad central sympathetic innervation of the kidney. The neurogenic inflammation within the spinal cord inherent to the PRV tracing method causes an inflammatory reaction within the bladder. This can be due to increased sympathetic nerve activity, followed by peripheral, neurogenically mediated inflammation.

c-Fos expression in the spinal cord after acute sacral segmental nerve stimulation.

AIMS: Sacral nerve stimulation (SNS) can provide subjective and objective relief of pelvic pain and chronic voiding symptoms, but its mechanism is poorly understood. It is well known that a noxious stimulus applied to one part of the body can reduce the response to a subsequent stimulus elsewhere in the body. This phenomenon, known as diffuse noxious inhibitory controls (DNIC), seems to be the mechanism by which pain can be reduced by concurrent noxious stimulation. METHODS: On the basis of the DNIC concept, we investigated the expression of a protein product of proto-oncogene c-Fos (c-Fos) in the rat spinal cord after acute electrical stimulation of the sacral segmental nerve with or without lower urinary tract irritation. Adult male Sprague-Dawley rats were treated either by sacral nerve stimulation (SNS) from the S1 sacral foramen or chemical irritation of the lower urinary tract (LUT) or both. Rats were perfused transcardially, and spinal cords were removed and processed for c-Fos immunohistochemistry. c-Fos expression in the central nervous system was detected by immunohistochemistry by using the avidin-biotin technique. The number of c-Fos-positive cells and their locations in the spinal cord were evaluated. RESULTS: SNS and LUT irritation resulted in significant increases in c-Fos-positive cells in L6 and S1 spinal segments. In the animals treated by SNS and LUT irritation, counts of c-Fos-positive cells in L6 and S1 segments were significantly smaller than expected. Distribution and number of c-Fos-positive cells in rats that received SNS and LUT irritation were almost the same as those induced by SNS alone in the S1 segment. CONCLUSIONS: SNS alone caused a near maximal response in c-Fos expression such that adding LUT irritation did not cause a linear increase in c-Fos. Subsequent LUT irritation could not induce additional expression of c-Fos within the spinal cord.