Future perspectives for surgical research in Germany

Background

During the last two decades, the complexity of surgical patient care has increased dramatically. Nonetheless, there is substantial need to improve the quality of surgical research in Germany.

Purpose

Herein, we present the current concepts of the German Society of Surgery, the Section of Surgical Research, the Study Center of the German Surgical Society, and the German Surgical Trial Network (CHIR-Net) and their perspectives to promote young surgeons for a career in academic surgery and to improve the quality of surgical research in experimental studies as well as in clinical trials. The concepts include also education, teaching, and mentoring in order to strengthen the research profile of surgical departments and surgical research institutes.

Conclusions

We feel that realization of these concepts should guarantee the survival of the surgeon-scientist across all surgical subspecialties, increase the attractiveness of academic positions in surgery, and promote translational research from bench to bedside with a benefit for patient care.     

Is there an anti-androgen withdrawal syndrome for enzalutamide?

Background

The anti-androgen withdrawal syndrome (AAWS) can be seen in one-third of patients after discontinuation of first-generation non-steroidal anti-androgen therapy. With the introduction of new agents for anti-androgen therapy as well as alternate mechanisms of action, new therapeutic options before and after docetaxel chemotherapy have arisen (Ohlmann et al. in World J Urol 30(4):495–503, 2012). The question regarding the occurrence of an enzalutamide withdrawal syndrome (EWS) has not been evaluated yet. In this study, we assess prostate-specific antigen (PSA) response after discontinuation of enzalutamide.

Methods

In total 31 patients with metastatic castration-resistant prostate cancer (mCRPC) underwent an enzalutamide withdrawal and were evaluated. Data were gathered from 6 centres in Germany. Patients with continuous oral administration of enzalutamide with rising serum PSA levels were evaluated, starting from enzalutamide withdrawal until subsequent therapy was initiated, follow-up ended or death of the patient occurred. Statistical evaluation was performed applying one-sided binomial testing using R-statistical software, version 3.0.1.

Results

Mean withdrawal follow-up was 6.5 weeks (range 1–26.1 weeks). None of the 31 patients showed a PSA decline. Mean relative PSA rise over all patients was 73.9 % (range 0.5–440.7 %) with a median of 44.9 %.

Conclusions

If existent, an AAWS is at least very rare for enzalutamide in patients with mCRPC after taxane-based chemotherapy and does not play a clinical role in this setting. This may be attributed to the different pharmacodynamics of enzalutamide. Longer duration of therapy or a longer withdrawal interval may reveal a rare EWS in the future.     

SDF‐1/CXCR4/CXCR7 is pivotal for vascular smooth muscle cell proliferation and chronic allograft vasculopathy

Chronic rejection remains a major obstacle in transplant medicine. Recent studies suggest a crucial role of the chemokine SDF‐1 on neointima formation after injury. Here, we investigate the potential therapeutic effect of inhibiting the SDF‐1/CXCR4/CXCR7 axis with an anti‐SDF‐1 Spiegelmer (NOX‐A12) on the development of chronic allograft vasculopathy. Heterotopic heart transplants from H‐2bm12 to B6 mice and aortic transplants from Balb/c to B6 were performed. Mice were treated with NOX‐A12. Control animals received a nonfunctional Spiegelmer (revNOX‐A12). Samples were retrieved at different time points and analysed by histology, RT‐PCR and proliferation assay. Blockade of SDF‐1 caused a significant decrease in neointima formation as measured by intima/media ratio (1.0 ± 0.1 vs. 1.8 ± 0.1, P < 0.001 AoTx; 0.35 ± 0.05 vs. 1.13 ± 0.27, P < 0.05 HTx). In vitro treatment of primary vascular smooth muscle cells with NOX‐A12 showed a significant reduction in proliferation (0.42 ± 0.04 vs. 0.24 ± 0.03, P < 0.05). TGF‐β, TNF‐α and IL‐6 levels were significantly reduced under SDF‐1 inhibition (3.42 ± 0.37 vs. 1.67 ± 0.33, P < 0.05; 2.18 ± 0.37 vs. 1.0 ± 0.39, P < 0.05; 2.18 ± 0.26 vs. 1.6 ± 0.1, P < 0.05). SDF‐1/CXCR4/CXCR7 plays a critical role in the development of chronic allograft vasculopathy (CAV). Therefore, pharmacological inhibition of SDF‐1 with NOX‐A12 may represent a therapeutic option to ameliorate chronic rejection changes.     

Long-term bowel disorders following radial cystectomy: an underestimated issue?

Purpose

Patients after radical cystectomy (RC) frequently complain about bowel disorders (BDs). Reports addressing related long-term complications are sparse. This cross-sectional study assessed changes in bowel habits (BH) after RC.

Methods

A total of 89 patients with a minimum follow-up ≥1 year after surgery were evaluated with a questionnaire. Patients with BD prior to surgery were excluded. Symptoms such as diarrhea, constipation, bloating/flatulence, incomplete defecation, uncontrolled stool loss, and impact on quality of life (QoL) were assessed.

Results

A total of 46.1 % of patients reported changes in BH; however, only 25.8 % reported experiencing related dissatisfaction. Primary causes of dissatisfaction were diarrhea and uncontrolled stool loss. The most common complaints were bloating/flatulence and the feeling of incomplete defecation, but these symptoms did not necessarily lead to dissatisfaction or impairment in quality of life. No difference was identified between an orthotopic neobladder and ileal conduit, and even patients without bowel surgery were affected. QoL, health status, and energy level were significantly decreased in unsatisfied patients.

Conclusions

About 25 % of patients complain about BDs after RC. More prospective studies assessing symptoms, comorbidities, and dietary habits are necessary to address this issue and to identify strategies for follow-up recommendations.

     

Hospital Frailty Risk Score Outperforms Current Risk Stratification Models in Primary Total Hip and Knee Arthroplasty

BackgroundModels for risk stratification and prediction of outcome, such as the Charlson Comorbidity Index (CCI), the Elixhauser Comorbidity Method (ECM), the 5-factor modified Frailty Index (mFI-5), and the Hospital Frailty Risk Score (HFRS) have been validated in orthopedic surgery. The aim of this study is to compare the predictive power of these models in total hip and knee replacement.MethodsIn a retrospective analysis of 8250 patients who had undergone total joint replacement between 2011 and 2019, CCI, ECM, mFI-5, and HFRS were calculated for each patient. Receiver operating characteristic curve plots were generated and the area under the curve (AUC) was compared between each score with regard to adverse events such as transfusion, surgical, medical, and other complications. Multivariate logistic regression models were used to assess the relationship among risk stratification models, demographic factors, and postoperative adverse events.ResultsIn prediction of surgical complications, HFRS performed best (AUC: 0.719, P < .001), followed by ECM (AUC: 0.578, P < .001), mFI-5 (AUC: 0.564, P = .003), and CCI (AUC: 0.555, P = .012). With regard to medical complications, other complications, and transfusion, HFRS also was superior to ECM, mFI-5, and CCI. Multivariate logistic regression analyses revealed HFRS as an independent risk stratification model associated with all captured adverse events (P ≤ .001).ConclusionThe HFRS is superior to current risk stratification models in the context of total joint replacement. As the HRFS derives from routinely collected administrative data, healthcare providers can identify at-risk patients without additional effort or expense.     

EAU Guidelines on Urethral Trauma

Context

These guidelines were prepared on behalf of the European Association of Urology (EAU) to assist urologists in the management of traumatic urethral injuries.

Objective

To determine the optimal evaluation and management of urethral injuries by review of the world's literature on the subject.

Evidence acquisition

A working group of experts on Urological Trauma was convened to review and summarize the literature concerning the diagnosis and treatment of genitourinary trauma, including urethral trauma. The Urological Trauma guidelines have been based on a review of the literature identified using on-line searches of MEDLINE and other source documents published before 2009. A critical assessment of the findings was made, not involving a formal appraisal of the data. There were few high-powered, randomized, controlled trials in this area and considerable available data was provided by retrospective studies. The Working Group recognizes this limitation.

Evidence synthesis

The full text of these guidelines is available through the EAU Central Office and the EAU website (www.uroweb.org). This article comprises the abridged version of a section of the Urological Trauma guidelines.

Conclusions

Updated and critically reviewed Guidelines on Urethral Trauma are presented. The aim of these guidelines is to provide support to the practicing urologist since urethral injuries carry substantial morbidity. The diversity of urethral injuries, associated injuries, the timing and availability of treatment options as well as their relative rarity contribute to the controversies in the management of urethral trauma.