Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53

The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1α (DD1α), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1α appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1α-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1α thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses

Current practice patterns of perioperative cystectomy management in Germany: a questionnaire survey

Zusammenfassung Hintergrund und Zielsetzung Die radikale Zystektomie (RCX) ist die kurative Standardbehandlung fur muskelinvasive Harnblasenkarzinome. Aufgrund des operativen Ausma ss es und der damit verbundenen komplexen stationaren Betreuung ist die RCX mit hoher Morbiditat und Mortalitat verbunden. Ziel war es, Daten aus dem klinischen Alltag zur gegenwartigen Praxis des perioperativen Managements zu erfassen. Methoden Mitglieder der DGU und der German Society of Residents in Urology beantworteten anonym einen 24 Fragen umfassenden Online-Fragebogen. Gegenstand waren sowohl klinisch relevante Aspekte der gegenwartigen EAU/DGU-Leitlinien als auch kontrovers diskutierte klinische Fragen. Ergebnisse Durch die Teilnehmer konnten mindestens 19% aller infrage kommenden deutschen Zentren erfasst werden. Mehrheitlich wird das praoperative Staging mittels CT-Urografie und CT-Thorax durchgefuhrt. Die meistgenutzte Antibiotikaprophylaxe umfasst ein Drittgenerations-Cephalosporin plus Metronidazol (46%), welche im Median fur 5 Tage verabreicht werden. Harnleiterschienen (HS) werden im Mittel beim Ileumconduit am 11. und bei der Neoblase am 12.Tag nach RCX entfernt. Gemessen an Surrogatparametern wie oraler Darmvorbereitung, Beginn des Kostaufbaus und Einsatz einer Magensonde sind aktuelle Fast-Track-Konzepte noch nicht allgemein verbreitet (e oder Anzahl der Eingriffe assoziiert. Abstract Objective Radical cystectomy (RCX) is the standard treatment for muscle-invasive and treatment-refractory non-invasive bladder cancer, but that is associated with high morbidity. We now survey current practice patterns on perioperative management among German urological departments of all sizes Methods Members of the German Association of Urology and the German Society of Residents in Urology (GeSRU) were contacted by email and asked to answer a 24-item online questionnaire covering clinically relevant aspects of current guidelines and controversies. Results Responses were obtained from at least 19% of all German urological centers. About 60% performed preoperative staging using CT urography and chest CT. The most common perioperative antibiotic prophylaxis was a third generation cephalosporin combined with metronidazole (46%), administered for a median of 5 days. Stentograms for ileal conduit and neobladder are routinely performed in 38% and 55% of patients, respectively. Ureteral stents were usually removed 11-12 days after the procedure (ileal conduit and neobladder). Based on the surrogate parameters of preoperative bowel preparation, postoperative start of oral nutrition and use of nasogastric tube, fast-track concepts such as ERAS were not generally established (<50%). Robot-assisted cystectomy appears to be performed in 15% of German urological centers and was associated with the number of performed cystectomies (p<0.001). Conclusions Most aspects of perioperative management in cystectomy patients - staging diagnostics, use of antibiotics, stent removal - are performed in accordance with current guidelines. Other clinical questions such as stent imaging before removal and fast track concepts are handled heterogeneously. Guideline-adherence was not associated with hospital size or number of procedures performed

Acceptance of Adjuvant and Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer in Germany: A Survey of Current Practice

Background: Guidelines support the use of neoadjuvant (NAC) and adjuvant (AC) chemotherapy in muscle-invasive bladder cancer. However, data from North America reported the underutilization of NAC in favor of AC despite the lower level of scientific evidence supporting AC. We aimed to assess current practice patterns of NAC and AC in Germany. Methods: A 15-question online survey was developed and sent via email newsletters to members of the German Association of Urology and of the German Society of Residents in Urology in October 2016 to analyze current practice patterns. Results: The survey yielded 141 individual responses from 61 different German urology departments. Eighty-nine (69.0%) and 119 (93.0%) participants were stated to regularly use NAC and AC respectively. The number of participants who were stated to use NAC and AC regularly was not associated with the type of institution (academic vs. nonacademic), number of hospital beds, and number of cystectomies performed annually. Gemcitabine/cisplatin combination chemotherapy was named as the primarily used NAC regimen by 80 (95%) respondents. The median number of administered cycles was 3 for NAC and 4 for AC. In the case of cisplatin ineligibility, combination chemotherapy with gemcitabine/carboplatin was the most common regimen. Respondents stated that chemotherapy was generally administered by urologists (81% for NAC and 85% for AC). Conclusions: Our survey of current practice shows a high acceptance rate of NAC in Germany, which was independent of the type of institution. Although the scientific level of evidence for AC is lower, it still seems to be more widely accepted than NAC. NAC and AC were generally administered by urologists. (C) 2018 S. Karger AG, Base

Websites on Bladder Cancer: an Appropriate Source of Patient Information?

A growing number of patients search for health information online. An early investigation of websites about bladder cancer (BCa) revealed mostly incomplete and particularly inaccurate information. We analyzed the quality, readability, and popularity of the most frequented websites on BCa. An Internet search on www.google.com was performed for the term bladder cancer. After selecting the most frequented websites for patient information, HONcode quality certification, Alexa popularity rank, and readability scores (according to US grade levels) were investigated. A 36-point checklist was used to assess the content according to the EAU guidelines on BCa, which was categorized into seven topics. The popularity of the 49 websites analyzed was average, with a median Alexa popularity rank of 41,698 (interquartile range [IQR] 7-4,671,246). The readability was rated difficult with 11 years of school education needed to understand the information. Thirteen (27%) websites were HONcode certified. Out of 343 topics (seven EAU guideline topics each on 49 websites), 79% were mentioned on the websites. Of these, 10% contained incorrect information, mostly outdated or biased, and 34% contained incomplete information. Publically provided websites mentioned more topics per website (median [IQR] 7 [5.5-7] vs. 5.5 [3.3-7]; p=0.022) and showed less incorrect information (median [IQR] 0 [0-1] vs. 1 [0-1]; p=0.039) than physician-provided websites. Our study revealed mostly correct but partially incomplete information on BCa websites for patients. Physicians and public organizations should strive to keep their website information up-to-date and unbiased to optimize patients' health literacy