Vergleich der Frühzystektomie mit der Zystektomie beim muskelinvasiven Karzinom der Harnblase hinsichtlich postoperativer Komplikationen und Outcome

Die Frage nach dem richtigen Zeitpunkt einer Zystektomie bei Patient:innen mit Blasenkarzinom wird noch immer kontrovers diskutiert. Zum einen ist eine Lebensverlängerung nach der Operation beschrieben, gleichzeitig muss bei der Entscheidungsfindung aber auch an eine potenzielle Minderung der Lebensqualität durch perioperative Komplikationen und Revisions-Operationen gedacht werden. Die vorliegende Studie vergleicht das Outcome, Überleben und die Komplikationen der Zystektomie im nichtmuskelinvasiven und im muskelinvasiven Stadium. Dazu wurden in einer retrospektiven, monozentrischen Studie Daten von 523 Patient:innen gesammelt und statistisch ausgewertet, die sich zwischen 2008 und 2018 im Caritas-Krankenhaus St. Josef in Regensburg für eine Zystektomie vorstellten. Bei 73,2% der Patient:innen kam es zu mindestens einer Frühkomplikation (innerhalb der ersten 90 Tage postoperativ), wobei es sich bei etwas mehr als der Hälfte (53,8%) um Major-Komplikationen nach Clavien-Dindo-Klassifikation handelte. Zu frühen Revisionsoperationen kam es bei 32,7% der Patient:innen. Außerdem erlitten 58,6% der Patient:innen Spätkomplikationen (über 90 Tage postoperativ), wobei es sich bei 49,3% um Major-Komplikationen handelte, und 27,6% mussten sich späten Revisionsoperationen unterziehen. Im Vergleich waren die beiden Zystektomie- Zeitpunkte hinsichtlich der Komplikationen annähernd gleichwertig. So hatten Patient:innen mit Frühzystektomie im Vergleich zur sekundären Zystektomie seltener gewisse Frühkomplikationen sowie eine niedrigere Anzahl an Frühkomplikationen, dafür aber etwas häufiger einzelne Spätkomplikationen, welche vor allem die Harnableitung betrafen. Bei Betrachtung des Outcomes hatten Patient:innen mit Frühzystektomie im Vergleich zu Patient:innen mit Zystektomie bei MIBC einen deutlichen Überlebensvorteil mit einem mittleren RFS, CSS und OS von 91,406 (±7,052) vs. 56,910 (±4,827) Monaten, 108,196 (±4,938) vs. 75,690 (±5,945) Monaten und 95,090 (±6,195) vs. 54,005 (±4,467) Monaten. Die weitere Entscheidung zwischen Frühzystektomie und konservativer Therapie zum gleichen Zeitpunkt bedarf weiterer Untersuchungen und Diskussion, jedoch zeigen die vorliegenden Daten, dass Patient:innen von einer frühen Zystektomie profitieren und im Vergleich mit der Zystektomie bei MIBC keinen wesentlichen Nachteil hinsichtlich der Komplikationen haben

Short-Term and Long-Term Morbidity after Radical Cystectomy in Patients with NMIBC and Comparison with MIBC: Identifying Risk Factors for Severe Short-Term Complications

Introduction: RC represents a viable treatment option for certain NMIBC patients. However, studies investigating morbidity in the context of RC for NMIBC are scarce. The goal of the current study was to assess and compare morbidity after RC performed in patients with NMIBC and patients with MIBC and to identify risk factors for severe short-term complications. Methods: Medical records of 521 patients who underwent RC for bladder cancer were retrospectively reviewed. Patients were divided into patients with NMIBC and patients with MIBC. The groups were compared and risk factors for severe complications were identified. Results: RC for NMIBC was performed in 123 patients (23.6%). Histological upstaging was seen in 47 NMIBC patients (38.2%) and in 231 MIBC patients (58%, p < 0.001). OS was 29.8% and CSS was 15.5%. Both endpoints were higher for RC for MIBC (p < 0.001). More complications affecting the urinary diversion were seen with RC for NMIBC (p = 0.033) and more continent urinary diversions (p = 0.040) were performed in those patients. Obesity (p = 0.008), a higher ASA score (p = 0.004), and preoperative medical drug anticoagulation (p = 0.025) were risk factors for severe short-term morbidity after both, RC for NMIBC and for MIBC. Conclusion: Patients who underwent RC for NMIBC are exposed to a comparably high perioperative risk than patients with MIBC. RC seems to be a viable treatment option for certain NMIBC patients with a significant histological upstaging in both groups. In patients with obesity, a high ASA score, and with medical drug anticoagulation, the indication for surgery should be confirmed especially strict and possible treatment alternatives should be considered particularly thorough

Combined Model of Quantitative Evaluation of Chest Computed Tomography and Laboratory Values for Assessing the Prognosis of Coronavirus Disease 2019

Purpose To assess the prognostic power of quantitative analysis of chest CT, laboratory values, and their combination in COVID-19 pneumonia. Materials and Methods Retrospective analysis of patients with PCR-confirmed COVID-19 pneumonia and chest CT performed between March 07 and November 13, 2020. Volume and percentage (PO) of lung opacifications and mean HU of the whole lung were quantified using prototype software. 13 laboratory values were collected. Negative outcome was defined as death, ICU admittance, mechanical ventilation, or extracorporeal membrane oxygenation. Positive outcome was defined as care in the regular ward or discharge. Logistic regression was performed to evaluate the prognostic value of CT parameters and laboratory values. Independent predictors were combined to establish a scoring system for prediction of prognosis. This score was validated on a separate validation cohort. Results 89 patients were included for model development between March 07 and April 27, 2020 (mean age: 60.3 years). 38 patients experienced a negative outcome. In univariate regression analysis, all quantitative CT parameters as well as C-reactive protein (CRP), relative lymphocyte count (RLC), troponin, and LDH were associated with a negative outcome. In a multivariate regression analysis. PO, CRP, and RLC were independent predictors of a negative outcome. Combination of these three values showed a strong predictive value with a C-index of 0.87. A scoring system was established which categorized patients into 4 groups with a risk of 7 %, 30 %, 67%, or 100% for a negative outcome. The validation cohort consisted of 28 patients between May 5 and November 13, 2020. A negative outcome occurred in 6 % of patients with a score of 0, 50% with a score of 1, and 100 % with a score of 2 or 3. Conclusion The combination of PO, CRP, and RLC showed a high predictive value for a negative outcome. A 4-point scoring system based on these findings allows easy risk stratification in the clinical routine and performed exceptionally in the validation cohort

CT Features of COVID-19 Pneumonia Differ Depending on the Severity and Duration of Disease

Background CT is important in the care of patients with COVID-19 pneumonia. However, CT morphology can change significantly over the course of the disease. To evaluate the CT morphology of RT-PCR-proven COVID-19 pneumonia in a German cohort with special emphasis on identification of potential differences of CT features depending on duration and severity of disease. Method All patients with RT-PCR-proven COVID-19 pneumonia and chest CT performed between March 1 and April 15, 2020 were retrospectively identified. The CT scans were evaluated regarding the presence of different CT features (e.g. ground glass opacity, consolidation, crazy paving, vessel enlargement, shape, and margin of opacifications), distribution of lesions in the lung and extent of parenchymal involvement. For subgroup analyses the patients were divided according to the percentage of parenchymal opacification (0-33 %, 34-66 %, 67-100 %) and according to time interval between symptom onset and CT date (0-5 d, 6-10 d, 11-15 d, > 15 d). Differences in CT features and distribution between subgroups were tested using the Mantel-Haenszel Chi Squared for trend. Results The frequency of CT features (ground glass opacity, consolidation, crazy paving, bronchial dilatation, vessel enlargement, lymphadenopathy, pleural effusion) as well as pattern of parenchymal involvement differed significantly depending on the duration of disease and extent of parenchymal involvement. The early phase of disease was characterized by GGO and to a lesser extent consolidation. The opacifications tended to be round and to some extent with sharp margins and a geographic configuration. The vessels within/around the opacifications were frequently dilated. Later on, the frequency of consolidation and especially crazy paving increased, and the round/geographic shape faded. After day 15, bronchial dilatation occurred, and lymphadenopathy and pleural effusion were seen more frequently than before. Conclusion The prevalence of CT features varied considerably during the course of disease and depending on the severity of parenchymal involvement. Radiologists should take into account the time interval between symptom onset and date of CT and the severity of disease when discussing the likelihood of COVID-19 pneumonia based on CT morphology. Key Points: The frequency of CT features and pattern of parenchymal involvement vary depending on the duration and extent of COVID-19 pneumonia. The early phase is characterized by GGO and consolidation which demonstrate a round shape and at least to some extent have sharp margins and a geographic configuration. The frequency of consolidation and especially crazy paving increases during the course of disease.. Beyond day 15 after symptom onset, bronchial dilatation occurs. Radiologists should take into account the duration and severity of disease when considering COVID-19 pneumonia. Citation Format. Schaible J, Meiler S, Poschenrieder F et al. CT Features of COVID-19 Pneumonia Differ Depending on the Severity and Duration of Disease. Fortschr Rontgenstr 2020; DOI 10.1055/a-1293-916

A Poly-ADP-Ribose Trigger Releases the Auto-Inhibition of a Chromatin Remodeling Oncogene

International audienceDNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain with the ATPase module mediates auto-inhibition. PARP1 activation suppresses this inhibitory interaction. Crucially, release from auto-inhibition requires a poly-ADP-ribose (PAR) binding macrodomain. We identify tri-ADP-ribose as a potent PAR-mimic and synthetic allosteric effector that abrogates ATPase-macrodomain interactions, promotes an ungated conformation, and activates the remodeler’s ATPase. ALC1 fragments lacking the regulatory macrodomain relax chromatin in vivo without requiring PARP1 activation. Further, the ATPase restricts the macrodomain’s interaction with PARP1 under non-DNA damage conditions. Somatic cancer mutants disrupt ALC1’s auto-inhibition and activate chromatin remodeling. Our data show that the NAD+-metabolite and nucleic acid PAR triggers ALC1 to drive chromatin relaxation. Modular allostery in this oncogene tightly controls its robust, DNA-damage-dependent activation