Adherence to the EAU guideline recommendations for systemic chemotherapy in penile cancer: results of the E-PROPS study group survey.

OBJECTIVES: To validate the adherence of urologists to chemotherapy recommendations given in the EAU guidelines on PeCa. The European Association of Urology (EAU) guidelines on penile cancer (PeCa) are predominantly based on retrospective studies with low level of evidence. MATERIALS AND METHODS: A 14-item-survey addressing general issues of PeCa treatment was developed and sent to 45 European hospitals. 557 urologists participated in the survey of which 43.5%, 19.3%, and 37.2% were in-training, certified, and in leading positions, respectively. Median response rate among participating departments was 85.7% (IQR 75-94%). Three of 14 questions addressed clinical decisions on neoadjuvant, adjuvant, and palliative chemotherapy. Survey results were analyzed by bootstrap-adjusted multivariate logistic-regression-analysis to identify predictors for chemotherapy recommendations consistent with the guidelines. RESULTS: Neoadjuvant, adjuvant, and palliative chemotherapy was recommended according to EAU guidelines in 21%, 26%, and 48%, respectively. For neoadjuvant chemotherapy, urologists holding leading positions or performing chemotherapy were more likely to recommend guideline-consistent treatment (OR 1.85 and 1.92 with p(bootstrap) = 0.007 and 0.003, respectively). Supporting resources (i.e., guidelines, textbooks) were used by 23% of survey participants and significantly improved consistency between treatment recommendations and Guideline recommendations in all chemotherapy settings (p(bootstrap) = 0.010-0.001). Department size and university center status were no significant predictors for all three endpoints. CONCLUSIONS: In this study, we found a very low rate of adherence to the EAU guidelines on systemic treatment for PeCa. Further investigations are needed to clarify whether this missing adherence is a consequence of limited individual knowledge level or of the low grade of guideline recommendations.

[Personal Factors of the Bio-Psycho-Social Model (WHO): A Revised Classification by the German Society for Social Medicine and Prevention (DGSMP)]. / Personbezogene Faktoren im bio-psycho-sozialen Modell der WHO: Systematik der Deutschen Gesellschaft für Sozialmedizin und Prävention (DGSMP).

BACKGROUND: In 2010, the ICF working group of Faculty II "Applied Social Medicine and Rehabilitation" of the German Society for Social Medicine and Prevention, DGSMP proposed a classification of personal factors (PF) for the German-speaking area. Meanwhile, the International Classification of Functioning, Disability and Health (ICF) and WHO's bio-psycho-social model were increasingly integrated into the German Social Code (Book IX for Rehabilitation and Participation). It was a legislative decision that the needs assessment for the rehabilitation process must be "comprehensive". AIM: This publication aims to present an updated classification of PF to support the socio-medical assessment. For this purpose other published papers proposing a classification of PF were analyzed, especially the publication of Geyh et al. METHODS: The multiprofessional working group re-examined the basic structure, consistency and selection of factors of the 2010 classification using a qualitative approach and modified them if meaningful and necessary. The principles for the selection of factors were the same as in the 2010 publication (comprehensive, manageable, universal, impartial, relevant, unambiguous, focusing on finality, not regarding causality and non-discriminatory). RESULTS: A fundamental revision was not necessary; the basic structure remained primarily unchanged. Some items were included, excluded, summarized, shifted and editorially or content-related altered. Legal expertise shows that the classification of PF and their individual use for the socio-medical assessment, if necessary for the individual rehabilitation allocation, incur no problems with regard to data-protection regulations. PERSPECTIVES: The revised classification is ready to support users to describe and document relevant influences of the life background of individuals in a structured manner. Thus, influences on functioning and participation can be described comprehensively and transparently based on the bio-psycho-social model. A justiciable allocation of benefits for persons with disabilities is facilitated.

Worth a second look: outcomes of patients with initial finding of regular renal tissue in CT-guided renal tumor biopsies.

INTRODUCTION AND OBJECTIVE: Renal tumor biopsy is recommended for histological diagnosis of radiologically indeterminate renal masses, to select patients with small-renal masses for surveillance approaches, before ablative treatments and to confirm metastatic spread of renal cell cancer (RCC), according to the EAU guidelines. We aimed to determine outcomes of patients with suspicious renal masses with initial finding of regular renal tissue in renal tumor biopsies. METHODS: Retrospective database analysis of 101 patients undergoing CT-guided-, percutaneous renal tumor biopsies in local anesthesia. RESULTS: In 23/101 patients, histopathologic evaluation of the biopsies showed regular renal tissue. Of these, two patients underwent simultaneous radiofrequency ablation (RFA), 2/23 underwent radical nephrectomy, despite negative biopsy because of radiological suspicious aspect. Overall, 12 patients underwent a second set of biopsies due to persistent clinical suspicion. Of these, five were diagnosed with RCC: three clear cell renal cell carcinoma (ccRCC) and two papillary renal cell carcinoma (pRCC). Benign tumours were found in two patients. A lymphoma was found in two patients. In 3/12 patients, also the second set of biopsies showed regular renal tissue. CONCLUSION: An unsuspicious histology in CT-guided renal tumor biopsy does not preclude patients with suspicious renal masses from being diagnosed with malignancies.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

Management of advanced bladder cancer in the era of targeted therapies.

Systemic chemotherapy is the standard treatment of advanced and metastatic urothelial carcinoma of the bladder (UCB). Unfortunately, systemic chemotherapy is ineffective in a significant number of patients, while side effects occur frequently. Detailed molecular-genetic investigations revealed a broad heterogeneity of underlying genomic mutations in UCB and led to the detection of cancer-specific therapeutic targets. These findings may allow a more tailored and individualized patient-based therapy, focusing on specific genomic variations, which may cause chemo-resistance in patients progressing or relapsing after standard chemotherapy. Targeted therapies hold the potential to be more effective in inhibiting cancer cell growth and progression, as well as to cause fewer side effects. While targeted therapies have been successfully established in the treatment of various malignancies including renal cell carcinoma, the clinical impact of these modern treatment strategies still remains unsettled for UCB. In this review, we comprehensively summarize the most current and relevant findings on targeted therapy in advanced and metastatic UCB, elucidating chances and limitations and discussing future perspectives.

[Relevance of personal contextual factors of the ICF for use in practical social medicine and rehabilitation]. / Bedeutung der personbezogenen Faktoren der ICF für die Nutzung in der praktischen Sozialmedizin und Rehabilitation.

Personal contextual factors play an essential part in the model of the International Classification of Functioning, Disability and Health (ICF). The WHO has not yet classified personal factors for global use although they impact on the functioning of persons positively or negatively. In 2010, the ICF working group of the German Society of Social Medicine and Prevention (DGSMP) presented a proposal for the classification of personal factors into 72 categories previously arranged in 6 chapters. Now a positioning paper has been added in order to stimulate a discussion about the fourth component of the ICF, to contribute towards a broader and common understanding about the nature of personal factors and to incite a dialogue among all those involved in health care as well as those people with or with-out health problems in order to gain a comprehensive perspective about a person's condition.

Risk stratification of pT1-3N0 patients after radical cystectomy for adjuvant chemotherapy counselling.

BACKGROUND: In pT1-T3N0 urothelial carcinoma of the bladder (UCB) patients, multi-modal therapy is inconsistently recommended. The aim of the study was to develop a prognostic tool to help decision-making regarding adjuvant therapy. METHODS: We included 2145 patients with pT1-3N0 UCB after radical cystectomy (RC), naive of neoadjuvant or adjuvant therapy. The cohort was randomly split into development cohort based on the US patients (n=1067) and validation cohort based on the Europe patients (n=1078). Predictive accuracy was quantified using the concordance index. RESULTS: With a median follow-up of 45 months, 5-year recurrence-free and cancer-specific survival estimates were 68% and 73%, respectively. pT-stage, ge, lymphovascular invasion, and positive margin were significantly associated with both disease recurrence and cancer-specific mortality (P-values ≤ 0.005). The accuracies of the multivariable models at 2, 5, and 7 years for predicting disease recurrence were 67.4%, 65%, and 64.4%, respectively. Accuracies at 2, 5, and 7 years for predicting cancer-specific mortality were 69.3%, 66.4%, and 65.5%, respectively. We developed competing-risk, conditional probability nomograms. External validation revealed minor overestimation. CONCLUSION: Despite RC, a significant number of patients with pT1-3N0 UCB experience disease recurrence and ultimately die of UCB. We developed and externally validated competing-risk, conditional probability post-RC nomograms for prediction of disease recurrence and cancer-specific mortality.

[Personal factors of the ICF]. / Personbezogene Faktoren der ICF.

PURPOSE: The presentation aims at illustrating the draft proposal of personal factors of the ICF for German-speaking regions which has been published in 2010 by the working group ICF of Faculty II "Social Medicine and Rehabilitation" of the German Society for Social Medicine and Prevention, DGSMP. For this reason, each personal factor is illustrated by two examples. Thus, the benefit is intended to be convincing. METHODS: Applying a qualitative approach, the working group ICF consisting of members of various professions and institutions including a patients' representative selected for each item one example the factor serving as a facilitator and a second the factor serving as a barrier. RESULTS: The components of the personal factors, as proposed, are presented, each factor is accompanied by two examples. CONCLUSION: The presentation demonstrates the various possibilities of applying personal factors and intends to prove that the selection of items chosen makes sense. The process of a comprehensive discussion about the possible format of the component of personal factors in the ICF should lead to a further optimization of the proposal and the preparation of a discussion at an international level.

The current role of precision surgery in oligometastatic prostate cancer.

Oligometastatic prostate cancer (omPCa) is a novel intermediate disease state characterized by a limited volume of metastatic cells and specific locations. Accurate staging is paramount to unmask oligometastatic disease, as provided by prostate-specific membrane antigen-positron emission tomography. Driven by the results of prospective trials employing conventional and/or modern staging modalities, the treatment landscape of omPCa has rapidly evolved over the last years. Several treatment-related questions comprising the concept of precision strikes are under development. For example, beyond systemic therapy, cohort studies have found that cytoreductive radical prostatectomy (CRP) can confer a survival benefit in select patients with omPCa. More importantly, CRP has been consistently shown to improve long-term local symptoms when the tumor progresses across disease states due to resistance to systemic therapies. Metastasis-directed treatments have also emerged as a promising treatment option due to the visibility of oligometastatic disease and new technologies as well as treatment strategies to target the novel PCa colonies. Whether metastases are present at primary cancer diagnosis or detected upon biochemical recurrence after treatment with curative intent, targeted yet decisive elimination of disseminated tumor cell hotspots is thought to improve survival outcomes. One such strategy is salvage lymph node dissection in oligorecurrent PCa which can alter the natural history of progressive PCa. In this review, we will highlight how refinements in modern staging modalities change the classification and treatment of (oligo-)metastatic PCa. Further, we will also discuss the current role and future directions of precision surgery in omPCa.

Tissue-based molecular markers for renal cell carcinoma.

Since the introduction of targeted therapies in renal cell carcinoma (RCC), more individualized treatment options have become available. Molecular markers might support treatment planning due to more accurate individual risk stratification. Current molecular markers in RCC were reviewed to elucidate clinical impact and future perspectives. An English-language literature review of the Medline database (1990 to September 2010) of published data on tissue-based molecular markers and RCC was undertaken. Histological types, clinical and oncological behaviour are variable in renal masses. Molecular markers offer potential for additional information in tumour detection and diagnosis, prognostic and predictive values, as well as determination of therapeutic targets. Investigations on molecular biomarkers in RCC include hypoxia inducible factor (HIF-α), vascular endothelial growth factor (VEGF), carbonic anhydrase IX (CAIX), mammalian target of rapamycin (mTOR), survivin, B7-H1, p53, matrix metalloproteinases (MMP), Insulin-like growth factor II mRNA-binding protein 3 (IMP3), Ki-67, C-reactive protein (CRP), Vimentin, Fascin, platelet count, hemoglobin level and combinations of these factors. Although some markers offer promising results, utilization in daily practice is compromised due to limited specificity, predictive accuracy and tumour histology variablity. There is an imminent need for novel molecular markers that allow accurate histologic and biologic classification of RCC to improve upon current outcomes. It is very likely that a panel of molecular markers will be used to achieve a sufficient degree of certainty in order to guide clinical decisions. A large concerted effort is required to advance the field of RCC molecular marker through systematic discovery, verification, and validation.

[Treat-to-target from the patient perspective]. / "Treat-to-Target" aus Sicht der Betroffenen.

The international treat-to-target initiative including rheumatoid arthritis (RA) patients has defined remission or alternatively low disease activity as treatment goals. In Germany representatives of the medical profession, such as doctors, nurses and including the Deutsche Rheuma-Liga, are deliberating how to adapt and realize these goals in practice. The patient's perspective has to be taken into consideration as an outcome variable. Until now no combined patient reported outcome (PRO) score exists which is generally accepted by the scientific community and which puts the patient's perspective as the main primary outcome.Patients and doctors ought to decide jointly about the therapy goal remission/low disease activity and about other PROs and the planned strategy to achieve these goals. A precondition is that a sufficient timeframe is still available for this. The joint target of the medical profession and the Deutsche Rheuma-Liga is 1 rheumatologist per 50,000 adult inhabitants. An interdisciplinary and multidisciplinary treatment of RA patients is just as imperative as the expansion of patient training, information and self-management programs.

Effects of symptom reduction and psychotropic medication on cognitive impairment in depression.

BACKGROUND: Depression is related to cognitive performance. This follow-up study examines the influence of depression symptoms and psychopharmacological treatment on change in the cognitive performance of patients with depressive episodes over a 2-year period. SAMPLING AND METHODS: Sixty-two in- and outpatients with depression of varying severity (ICD-10: F31-F33) were examined in an open prospective naturalistic observational study with 3 points of measurement and tested by use of 3 computerized cognitive performance tests [Visual Attentiveness Test (VAT), Continuous Attention Test (CAT), Word Recognition Test (WRT)], while the psychotropic medication was classified by subclass and dosage. Statistical analysis was performed by random-effects regression models. RESULTS: The raw values of VAT speed, CAT speed and WRT quality improved over time. However, the positive time trend disappeared after the patients' clinical and personal characteristics were controlled for. The processing speed of the VAT was found to be negatively influenced by depressive symptoms. That of the CAT developed favorably with increasing level of education. The performance qualities of the VAT, WRT and CAT were positively related to the participants' educational level. The patients who received antipsychotic treatment performed worse on WRT quality than those who were not treated with antipsychotics. CONCLUSIONS: The cognitive performance was relatively stable during the treatment process and not affected by clinical characteristics or type of medication. Cognitive deficits in patients with depression could be a trait rather than a state marker.

[The role of the vesical imaging-reporting and data system (VI-RADS) for bladder cancer diagnostics-status quo]. / Bedeutung der VI-RADS-Klassifikation für die Bildgebung beim Harnblasenkarzinom ­ Stand der Dinge.

Initial clinical and pathological diagnostic workup of urinary bladder cancer is based on cystoscopy, transurethral resection of suspicious lesions, and computed tomography when indicated. Accurate staging is necessary for further therapeutic decision-making. This review summarizes the current status of multiparametric magnetic resonance imaging (mpMRI) and the vesical imaging-reporting and data system (VI-RADS) classification. MpMRI may improve the accuracy of assessment of local tumor invasion compared to conventional imaging alone. VI-RADS standardizes reporting of MRI staging and classifies the likelihood of muscle-invasive bladder cancer into five categories. Preliminary data suggest low interobserver variability. However, prospective multicenter studies are necessary to validate the VI-RADS classification. Progress in functional, molecular, and hybrid imaging may further improve the accuracy of clinical tumor and nodal staging for bladder cancer.

Obesity in acute alcoholic hepatitis increases morbidity and mortality.

BACKGROUND: Alcohol and obesity synergise to increase the risk of liver-related mortality. We examined the influence of adiposity on clinical outcomes in alcoholic hepatitis (AH) and the underlying inflammatory crosstalk between adipose tissue (AT) and the liver. METHODS: A cohort of 233 patients with AH from the UK and USA provided data to analyse the effects of obesity in AH. Body mass index was corrected for the severity of ascites, termed cBMI. Inflammatory and metabolic profiling was undertaken by proteome analysis of human serum samples. The effect of alcohol on adipose tissue and CXCL11 expression was studied in 3 T3-derived adipocytes and in mice using the high-fat diet-plus-binge ethanol model. FINDINGS: Obesity was common amongst patients with AH, seen in 19% of individuals. Obesity (HR 2.22, 95%CI 1.1-4.3, p = .022) and underweight (HR 2.38, 1.00-5.6, p = .049) were independently associated with mortality at 3 months. Proteome analysis demonstrated multiple metabolic and inflammatory factors differentially expressed in obese AH verse lean AH, with CXCL11 being the most elevated factor in obese AH. In vitro analysis of cultured adipocytes and in vivo analysis of mouse models showed that alcohol induced CXCL11 expression in AT, but not in liver. INTERPRETATION: Obesity is common in AH and associated with a greater than two-fold increase in short-term mortality. Obese AH is associated with a different inflammatory phenotype, with the greatest elevation in CXCL11. These data confirm that adiposity is clinically important in acute alcohol-related liver disease and illustrate the adipose-liver inflammatory axis in AH. FUND: This work was supported in part by an EASL Sheila Sherlock Physician Scientist Fellowship. The funder played no role in gathering or analysing data or writing the manuscript. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Commentary on "Detection and oncological effect of circulating tumor cells in patients with variant urothelial carcinoma histology treated with radical cystectomy."

OBJECTIVES: To investigate for the presence of circulating tumor cells (CTC) in patients with variant urothelial carcinoma of the bladder (UCB) histology treated with radical cystectomy (RC), and to determine their impact on oncological outcomes. PATIENTS AND METHODS: We, prospectively, collected data of 188 patients with UCB treated with RC without neoadjuvant chemotherapy. Pathological specimens were meticulously reviewed for pure and variant UCB histology. Preoperatively collected blood samples (7.5ml) were analyzed for CTC using the CellSearch system (Janssen, Raritan, NJ). RESULTS: Variant UCB histology was found in 47 patients (25.0%), most frequently of squamous cell differentiation (16.5%). CTC were present in 30 patients (21.3%) and 12 patients (25.5%) with pure and variant UCB histology, respectively. At a median follow-up of 25 months, the presence of CTC and nonsquamous cell differentiation were associated with reduced recurrence-free survival (RFS) and cancer-specific survival (pairwise P ≤ 0.016). Patients without CTC had better RFS, independent of UCB histology, than patients with CTC with any UCB histology (pairwise P<0.05). In multivariable analyses, the presence of CTC, but not variant UCB histology, was an independent predictor for disease recurrence (hazard ratio = 3.45, P<0.001) and cancer-specific mortality (hazard ratio = 2.62, P = 0.002). CONCLUSION: CTC are detectable in about a quarter of patients with pure or variant UCB histology before RC, and represent an independent predictor for outcomes, when adjusting for histological subtype. In addition, our prospective data confirm the unfavorable influence of nonsquamous cell-differentiated UCB on outcomes.

[Side effect management of tyrosine kinase inhibitors in urology : Gastrointestinal side effects]. / Nebenwirkungsmanagement von Tyrosinkinaseinhibitoren in der Urologie : Gastrointestinale Nebenwirkungen.

For approximately one decade, tyrosinkinase inhibitors (TKIs, smart drugs) have dramatically changed and improved the treatment of patients suffering from metastasized renal cell carcinoma. However, the different drugs have substantial side effects. Especially gastrointestinal symptoms may be problematic for patients. These side effects represent a challenge for the physician. On the one hand, dosage modifications and treatment interruption should be avoided to minimize the risk for progression. On the other hand, only mild side effects are tolerable for the patient. Based on a literature review, a clear overview of the incidence of possible side effects for the drugs axitinib, cabozantinib, pazopanib, sorafenib, and sunitinib is provided. Furthermore, we give a practical guide on how to prevent and treat the different gastrointestinal side effects. Finally, it is pointed out when dosage modifications or interruption of treatment are necessary and how to expeditiously re-escalate the treatment after mitigation of side effects.

[Infra- and supradiaphragmatic urethral injuries. Acute treatment]. / Infra- und supradiaphragmale Urethraverletzungen. Akute Therapie.

BACKGROUND: Urethral injuries are often caused by pelvic fractures or blunt trauma. Drainage of the urinary bladder is the first step of therapy. RESULTS: Urethral injuries are often caused by pelvic fractures or blunt trauma. Drainage of the urinary bladder is the first step of therapy. Standard procedure is the insertion of a suprapubic stent in stable patients without concomitant open injuries in the pelvis area. Endoscopic realignment is useful in patients with pelvic fracture, vaginal, rectal, or bladder injury, who require open surgery. Delayed repair by stricture excision and open urethroplasty with end-to-end anastomosis is the standard procedure.

The prognostic role of preoperative serum C-reactive protein in predicting the biochemical recurrence in patients treated with radical prostatectomy.

BACKGROUND: To assess the prognostic value of preoperative C-reactive protein (CRP) serum levels for prognostication of biochemical recurrence (BCR) after radical prostatectomy (RP) in a large multi-institutional cohort. METHODS: Data from 7205 patients treated with RP at five institutions for clinically localized prostate cancer (PCa) were retrospectively analyzed. Preoperative serum levels of CRP within 24 h before surgery were evaluated. A CRP level ⩾0.5 mg dl(-1) was considered elevated. Associations of elevated CRP with BCR were evaluated using univariable and multivariable Cox proportional hazards regression models. Harrel's C-index was used to assess prognostic accuracy (PA). RESULTS: Patients with higher Gleason score on biopsy and RP, extracapsular extension, seminal vesicle invasion, lymph node metastasis, and positive surgical margins status had a significantly elevated preoperative CRP compared to those without these features. Patients with elevated CRP had a lower 5-year BCR survival proportion as compared to those with normal CRP (55% vs 76%, respectively, P<0.0001). In pre- and postoperative multivariable models that adjusted for standard clinical and pathologic features, elevated CRP was independently associated with BCR (P<0.001). However, the addition of preoperative CRP did not improve the accuracy of the standard pre- and postoperative models for prediction of BCR (70.9% vs 71% and 78.9% vs 78.7%, respectively). CONCLUSIONS: Preoperative CRP is elevated in patients with pathological features of aggressive PCa and BCR after RP. While CRP has independent prognostic value, it does not add prognostically or clinically significant information to standard predictors of outcomes.