Konrad Wilhelm

Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R

Danger signals released upon cell damage can cause excessive immune-mediated tissue destruction such as that found in acute graft-versus-host disease (GVHD), allograft rejection and systemic inflammatory response syndrome. Given that ATP is found in small concentrations in the extracellular space under physiological conditions, and its receptor P2X7R is expressed on several immune cell types, ATP could function as a danger signal when released from dying cells. We observed increased ATP concentrations in the peritoneal fluid after total body irradiation, and during the development of GVHD in mice and in humans. Stimulation of antigen-presenting cells (APCs) with ATP led to increased expression of CD80 and CD86 in vitro and in vivo and actuated a cascade of proinflammatory events, including signal transducer and activator of transcription-1 (STAT1) phosphorylation, interferon-γ (IFN-γ) production and donor T cell expansion, whereas regulatory T cell numbers were reduced. P2X7R expression increased when GVHD evolved, rendering APCs more responsive to the detrimental effects of ATP, thereby providing positive feedback signals. ATP neutralization, early P2X7R blockade or genetic deficiency of P2X7R during GVHD development improved survival without immune paralysis. These data have major implications for transplantation medicine, as pharmacological interference with danger signals that act via P2X7R could lead to the development of tolerance without the need for intensive immunosuppression.

Postureteroscopic Lesion Scale: A New Management Modified Organ Injury Scale—Evaluation in 435 Ureteroscopic Patients

BACKGROUND AND PURPOSE Objective parameters for the classification of ureteral injuries and resulting indications for ureteral stent placement after ureteroscopy are lacking. We hereby present a new classification system including proof of interrater reliability and validation of recommendations for postoperative ureteral stent placement. PATIENTS AND METHODS The Postureteroscopic Lesion Scale (PULS) was applied in 435 patients undergoing ureteroscopy. Interrater reliability between three surgeons (junior resident, senior resident, and specialist) was evaluated in 112 patients. Postoperative ureteral stent placement was performed according to PULS. For follow-up with ultrasonography, we assumed hydronephrosis to be an indirect sign for significant postoperative ureteral obstruction. RESULTS No ureteral lesion was seen in 46.2% of patients (grade 0). A grade 1, 2, or 3 lesion was seen in 30.8%, 19.1%, and 3.9% of patients, respectively. No grade 4 or 5 lesions were observed in our series. Interrater reliability was high (Kendall W=0.91; mean Spearman Rho=0.86). This was particularly true between senior resident and specialist (Rho=0.95), compared with junior resident and senior resident or specialist (Rho=0.83, Rho=0.79, respectively). All patients with documented lesions had a Double-J stent placed. Indwelling time varied according to PULS. Results of a postoperative ultrasonographic follow-up could be obtained in 95.6% of cases. No patient showed clinical or sonographic signs of upper urinary tract obstruction. CONCLUSIONS According to these preliminary data for the clinical application of PULS, interrater reliability is high. Standardized empiric recommendations for the use and duration of postoperative stent placement after ureteroscopy might be useful in guiding urologists in this conversely discussed issue, ultimately preventing ureteral strictures as a late complication of ureteroscopy. These will have to be confirmed, however, by controlled trials in the future.

Clinical significance of residual fragments in 2015: impact, detection, and how to avoid them

PurposeResidual fragments are common after stone treatment. Little is known about clinical outcomes relevant to the patient. This comprehensive review of the literature highlights the impact of residual fragments, modes of detection, and treatment strategies to avoid residual fragments in shock wave therapy, ureteroscopy, and percutaneous nephrolithotomy.MethodsA comprehensive review of current literature was performed using PubMed®, MEDLINE®, Embase™, Ovid®, Google Scholar™, and the Cochrane Library. Publications relevant to the subject were retrieved and critically appraised.ResultsResidual fragments after treatment for urinary stones have a significant impact on a patient’s well-being and future course. (Ultra-) low-dose non-contrast computed tomography detects small residuals most reliably. In shock wave lithotripsy, adherence to basic principles helps to improve results. Various techniques and devices facilitate complete stone clearance in conventional and miniaturized percutaneous nephrolithotomy and (flexible) ureteroscopy. Promising new technologies in shock waves, lasers, and robotics (and potentially microrobotics) are on the horizon.ConclusionsResidual fragments are relevant to patients. Contemporary treatment of urolithiasis should aim at complete stone clearance.

Stereoscopic (3D) versus monoscopic (2D) laparoscopy: comparative study of performance using advanced HD optical systems in a surgical simulator model

PurposeTo compare task performances of novices and experts using advanced high-definition 3D versus 2D optical systems in a surgical simulator model.MethodsFifty medical students (novices in laparoscopy) were randomly assigned to perform five standardized tasks adopted from the Fundamentals of Laparoscopic Surgery (FLS) curriculum in either a 2D or 3D laparoscopy simulator system. In addition, eight experts performed the same tasks. Task performances were evaluated using a validated scoring system of the SAGES/FLS program. Participants were asked to rate 16 items in a questionnaire.ResultsOverall task performance of novices was significantly better using stereoscopic visualization. Superiority of performances in 3D reached a level of significance for tasks peg transfer and precision cutting. No significant differences were noted in performances of experts when using either 2D or 3D. Overall performances of experts compared to novices were better in both 2D and 3D. Scorings in the questionnaires showed a tendency toward lower scores in the group of novices using 3D.ConclusionsStereoscopic imaging significantly improves performance of laparoscopic phantom tasks of novices. The current study confirms earlier data based on a large number of participants and a standardized task and scoring system. Participants felt more confident and comfortable when using a 3D laparoscopic system. However, the question remains open whether these findings translate into faster and safer operations in a clinical setting.

A specific spectral signature of serum and plasma-derived extracellular vesicles for cancer screening

In cancer, extracellular vesicles (EV) contribute to tumor progression by regulating local and systemic effects. Being released into body fluids, EV may be used in nanomedicine as a valuable source for diagnostic biomarkers. In this work, infrared and Raman spectroscopy were used for comprehensive comparative analysis of cancer versus non-cancer EV and patient screening. Two different EV fractions enriched in exosomes and microvesicles were isolated by differential centrifugation from serum and plasma of cancer and non-cancer patients and from serum and plasma of a healthy donor. The EV fractions were then subjected to drop-coating deposition and drying on calcium fluoride substrates. Reduction of alpha-helix-rich proteins and enhancement of beta-sheet-rich proteins as a cancer-specific blood EV signature was determined, and subsequently this feature was applied for a pilot study aiming to detect prostate cancer in a test cohort of patients with high-grade prostate carcinoma and benign hypoplasia.

Bringing excellence into urology: How to improve the future training of residents?

Abstract The problem: The demographic development of society leads to an increased demand for physicians. Particularly in the surgical disciplines, there is a noticeably declining interest among graduates from medical schools worldwide. For reasons discussed in detail, this applies especially to urology. Solutions: We indicate possibilities on how to counteract this trend, by improving the training for urology residents. Whereas some major changes for the better have already been introduced into the curricula in some countries, others will have to be further specified in the future. This article gives an overview of the requirements of a specific training programme, from a planning phase to its certification. Aspects such as the selection of candidates, the goals of a good training programme, and an implementation strategy are presented. Essential elements of a urology resident programme for effective coaching, improving medical skills (e.g. in surgical laboratories), knowledge revision, progress evaluation, and retrospection are discussed critically, giving an understanding of the crucial requirements of a good and attractive education in urology. Conclusion: A structured and well organised training programme might attract additional medical students towards urology and contribute significantly to the further development of the speciality. This can be seen as an initiative to counteract the decline of urology as an attractive field of interest to upcoming generations of physicians, and therefore to ensure urological care of the highest quality that patients deserve.

Ultralow Radiation Exposure During Flexible Ureteroscopy in Patients With Nephrolithiasis—How Far Can We Go?

OBJECTIVE To evaluate the feasibility and clinical performance of a novel surgeon technique and protocol targeting ultralow fluoroscopy usage in retrograde intrarenal surgery (RIRS). MATERIALS AND METHODS All RIRS procedures between 2009 and 2015 for 10- to 20-mm renal calculi performed by the same 2 experienced urologists were eligible. All procedures were performed using a highly standardized step-by-step RIRS technique. This technique was modified by the ultralow radiation exposure RIRS protocol; herein, as much as possible of the standardized steps were performed without radiation control targeting ultralow fluoroscopy usage. Primary end points were fluoroscopy time and dose area product. Secondary end points were stone-free rate (SFR) and intraoperative complications according to Satava classification. End points were evaluated using scatter plots and linear regression model. RESULTS Overall, 174 procedures were assessed. Over the study period, fluoroscopy time and dose area product could be reduced from 167.7 s/318.4 cGy/cm2 in 2009 to 7.4 s/6.4 cGy/cm2 in 2015 (P <.001). SFR (66.7% in 2009; 100% in 2015) and complications (Satava 1 and 2: 28.5% and 4.8%, respectively) improved P <.1), and the surgical duration was reduced (91 minutes and 65 minutes, respectively, P <.001). CONCLUSION Our findings revealed a continuous reduction of the amount of radiation used by the implementation of a novel ultralow X-ray usage protocol. SFR, complications, and surgical duration all improved, demonstrating that the novel protocol is as effective as current methods. Exposure to ionizing radiation can be significantly reduced if the presented protocol is followed strictly.

The cumulative analgesic consumption score (CACS): evaluation of a new score to describe postsurgical analgesic consumption as a surrogate parameter for postoperative pain and invasiveness of surgical procedures

OBJECTIVE To validate and evaluate the applicability of a new score to describe postsurgical analgesic consumption in urological and surgical patients across different categories of pain medications and the invasiveness of medical interventions. MATERIALS AND METHODS The cumulative analgesic consumption score (CACS) was determined for two cohorts of patients split into three groups with surgeries involving clinically distinct levels of invasiveness (n = 2 x 60). Nonparametric statistical analyses were performed to determine differences between the CACS among the different groups and to assess the correlation between CACS and numeric rating scale (NRS) values for pain intensity. RESULTS The score was determined for postoperative days 1 and 2 and revealed median scores of 0 (0-11), 3 (0-22) and 10 (6-17) for UA (urological patients from group A), UB (group B) and UC (group C), respectively, and 4 (0-20), 8 (0-38) and 17 (7-68) for SA (surgical patients from group A, SB (group B) and SC (group C), respectively. CACS enabled reliable differentiation between groups involving different levels of invasiveness (p < 0.001). CACS and peak NRS values showed variable degrees of correlation, as expressed by levels of significance ranging from p < 0.001 to p = 0.34 (NS). CONCLUSIONS The CACS is a valid and easily applicable tool to describe postsurgical analgesic consumption in urological and surgical patients. It can be used as a surrogate parameter to assess postsurgical pain and the invasiveness of surgical procedures. These aspects may be measured to compare surgical procedures, in both clinical trials and clinical practice settings.

Level of evidence, sponsorship, conflict of interest policy and commercial impact of PubMed‐listed clinical urolithiasis‐related trials in 2014

To evaluate published trials on urolithiasis regarding level of evidence, type of sponsorship and declared conflicts of interest (COIs), and to elucidate a potential commercial impact.

Analgesia-free flexible ureteroscopic treatment and laser lithotripsy for removal of a large urinary stone: a case report

IntroductionUrinary stone formation is a frequent complication after continent urinary tract diversion and can require complex surgical management. Therapy options include open, percutaneous, transurethral, or transstomal stone fragmentation and extraction. The transstomal approach is considered to be one of the more complex treatment modalities. The patient’s individual anatomy, minor stoma diameter, and the existing continence mechanism in the majority of cases cause substantial technical challenges for the surgeon. We present here what we believe to be the first description of an analgesia-free flexible endoscopic removal of a large pouch stone in an out-patient care setting. Additionally, we provide a brief overview of competing techniques.Case presentationA 30-year-old Caucasian woman with a history of lower urinary tract reconstruction with an ileal pouch and a continent umbilical stoma was admitted to our department with pouch urolithiasis in the urinary reservoir. We employed a minimally invasive approach to extract the stone using flexible ureteroscopy via a modified access sheath and laser lithotripsy. No analgesia is needed with this procedure and it can be performed in an out-patient setting.ConclusionThe described clinical case highlights the difficulties of treating this high-incidence problem in patients with continent urinary diversions. Our presented technique is of particular interest to urologists and family doctors, and could improve the treatment of such patients by lowering the morbidity of the intervention.