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Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65–80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1–24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1–6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69–91%) vs. 59% (45–72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl).

Aims The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society for Gynaecology and Obstetrics (OEGGG) and the Swiss Society for Gynaecology and Obstetrics (SGGG) was to provide consensus-based recommendations for the diagnosis and treatment of endometriosis based on an evaluation of the relevant literature. Methods This S2k guideline represents the structured consensus of a representative panel of experts with different professional backgrounds commissioned by the Guideline Committee of the DGGG, OEGGG and SGGG. Recommendations Recommendations on the epidemiology, aetiology, classification, symptomatology, diagnosis and treatment of endometriosis are given and special situations are discussed.

We report the case of a 71 years old patient with chronic lymphocytic leukemia (CLL), who developed a rapidly progressing multi-fungal infection including mucormycosis of the central nervous system (CNS) during treatment with ibrutinib.On autopsy mucorales species were demonstrated intravascularly by histomorphology of several organs and lymph nodes and were characterized as Rhizomucor pusillus by polymerase-chain reaction (PCR) – analysis. In addition, invasive pulmonary Aspergillus fumigatus was found and also confirmed by PCR. To the best of our knowledge, this is the first confirmation of a multi-fungal sepsis and invasive CNS-infection with mucorales species under ibrutinib. Knowing the risk for invasive fungal disease in patients under ibrutinib, identifying the pathogen and early initiation of specific treatment is crucial for a good clinical outcome especially in mucormycosis. Keywords: Ibrutinib, Chronic lymphocytic leukemia, CLL, Aspergillosis, Mucormykosis, Cerebral infection

This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they received standard induction chemotherapy with or without lenalidomide. Bone marrow biopsies at diagnosis and before the 2nd induction cycle were obtained to assess the therapeutic impact on leukemic blasts and microenvironment. Increased bone marrow angiogenesis, as assessed by microvessel density (MVD), was found at AML diagnosis and differed significantly between the WHO categories. Morphological analysis revealed a higher initial MVD in AML with myelodysplasia-related changes (AML-MRC) and a more substantial decrease of microvascularization after lenalidomide exposure. A slight increase of T-bet-positive TH1-equivalents was identifiable under lenalidomide. In the subgroup of patients with AML-MRC, the progression-free survival differed between the two treatment regimens, showing a potential but not significant benefit of lenalidomide. We found no correlation between the cereblon genotype (the target of lenalidomide) and treatment response or prognosis. In conclusion, addition of lenalidomide may be beneficial to elderly patients suffering from AML-MRC, where it leads to a reduction of microvascularization and, probably, to an intensified specific T cell-driven anti-leukemic response. Supplementary Information The online version contains supplementary material available at 10.1007/s00277-021-04467-2.

Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43–0·74], p1 mm), IIIB, or IIIC (without in-transit metastasis), and with an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) via a central interactive voice response system to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for up to 18 doses or until disease recurrence or unacceptable toxicity. Randomisation was stratified according to disease stage and region, using a minimisation technique, and clinical investigators, patients, and those collecting or analysing the data were masked to treatment assignment. The two coprimary endpoints were recurrence-free survival in the intention-to-treat (ITT) population and in patients with PD-L1-positive tumours. The secondary endpoint reported here was distant metastasis-free survival in the ITT and PD-L1-positive populations. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37. Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to receive either pembrolizumab (n=514) or placebo (n=505). At an overall median follow-up of 42·3 months (IQR 40·5–45·9), 3·5-year distant metastasis-free survival was higher in the pembrolizumab group than in the placebo group in the ITT population (65·3% [95% CI 60·9–69·5] in the pembrolizumab group vs 49·4% [44·8–53·8] in the placebo group; HR 0·60 [95% CI 0·49–0·73]; p

Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer. In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage. Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512–895 ml]. Application of TachoSil® did not significantly reduce the total volume of axillary drainage [mean difference (MD) −110 ml, 95% CI −316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil®. The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625–35,880) with TachoSil® and 33,365 Swiss Francs (95% CI 31,771–34,961) without, p = 0.584]. In the TachoSil® group, length of stay was longer (MD 1 day, 95% CI 0.3–1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1–4) vs. 5.5 days (95% CI 2–11); p = 0.2]. TachoSil® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.

This work was supported by Cancer Research UK (EHW, TJ: C42738/A24868); National Institute of Health Research Cambridge Biomedical Research Centre (HE); National Institute of Health Research UK Academic Clinical Fellowship (CMC); and National Institutes of Health USA Cancer Center support grant (TJ: 5P30CA045508-31). Important oncological management decisions rely on kidney function assessed by serum creatinine-based estimated glomerular filtration rate (eGFR). However, no large-scale multicentre comparison of methods to determine eGFR in patients with cancer are available. To compare the performance of formulas for eGFR based on routine clinical parameters and serum creatinine not calibrated with isotope dilution mass spectrometry (non-IDMS), we studied 3,620 patients with cancer and 166 without cancer who had their GFR measured with an exogenous nuclear tracer at one of seven clinical centres. The mean measured GFR was 86 ml/min. Accuracy of all models was centre-dependent, reflecting inter-centre variability of non-IDMS creatinine measurements. CamGFR was the most accurate model for eGFR (root-mean-squared-error (RMSE) 17.3 ml/min) followed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) model (RMSE 18.2 ml/min).Important oncological management decisions rely on kidney function assessed by serum creatinine-based estimated glomerular filtration rate (eGFR). However, no large-scale multicentre comparison of methods to determine eGFR in patients with cancer are available. To compare the performance of formulas for eGFR based on routine clinical parameters and serum creatinine not calibrated with isotope dilution mass spectrometry (non-IDMS), we studied 3,620 patients with cancer and 166 without cancer who had their GFR measured with an exogenous nuclear tracer at one of seven clinical centres. The mean measured GFR was 86 ml/min. Accuracy of all models was centre-dependent, reflecting inter-centre variability of non-IDMS creatinine measurements. CamGFR was the most accurate model for eGFR (root-mean-squared-error (RMSE) 17.3 ml/min) followed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) model (RMSE 18.2 ml/min).Important oncological management decisions rely on kidney function assessed by serum creatinine–based estimated glomerular filtration rate (eGFR). However, no large-scale multicenter comparisons of methods to determine eGFR in patients with cancer are available. To compare the performance of formulas for eGFR based on routine clinical parameters and serum creatinine not calibrated with isotope dilution mass spectrometry, we studied 3620 patients with cancer and 166 without cancer who had their glomerular filtration rate (GFR) measured with an exogenous nuclear tracer at one of seven clinical centers. The mean measured GFR was 86 mL/min. Accuracy of all models was center dependent, reflecting intercenter variability of isotope dilution mass spectrometry–creatinine measurements. CamGFR was the most accurate model for eGFR (root-mean-squared error 17.3 mL/min) followed by the Chronic Kidney Disease Epidemiology Collaboration model (root-mean-squared error 18.2 mL/min). Publisher PDF

Introduction: The practice of carboplatin dosing is not concordant among different centres and oncologists. Some clinical guidelines recommend capping of the carboplatin dose at, for example, creatinine-clearance (Crea-Cl) of 125 mL/min because of concerns of excessive toxicity. Clinical data to support such recommendations are lacking, especially in patients with seminoma.Methods: This is a retrospective analysis of acute haematotoxicity of patients with stage I seminoma treated with adjuvant carboplatin area under the curve (AUC) 7 in routine practice in two Swiss centres in 2005-2015, and a comparison of incidence and grade (according to Common Terminology Criteria for Adverse Events v4.0) of haematological adverse events (hAEs) in patients with Crea-Cl 125 mL/min without dose capping.Results: 74 patients with 229 documented measurements were included (median 3/patient). A total of 151 hAEs occurred. Platelet nadir occurred earlier than median white cell/neutrophil count (median day 15 vs day 22; P125 mL/min versus those with Crea-Cl Conclusions: Toxicity after single-dose carboplatin AUC 7 is generally mild. No excess of toxicity occurs in patients with high Crea-Cl above 125 mL/min, and therefore dose capping is not routinely necessary. In addition, this study provides a rationale for efficient use of healthcare services without compromising patients' safety.

Purpose Thoracic ultrasound (TUS) has been successfully used in the diagnosis of community-acquired pneumonia. Little is known about its diagnostic potential in ventilator-associated pneumonia (VAP). The purpose of this study was to systematically describe the morphology and temporal changes of sonographic patterns in mechanically ventilated patients and to evaluate the diagnostic performance characteristics of TUS-based VAP diagnoses. Materials and methods Patients who were placed on invasive ventilation for reasons other than pneumonia and who were considered at risk for the development of VAP received daily TUS examinations while being closely monitored for the development of pneumonia. Results Fifty-seven patients were studied. The incidence of VAP was 21.1%. Sonographic patterns of reduced or absent lung aeration were found in 64.2% of examinations. The sonographic pattern of lung consolidation with either dynamic or static air bronchograms was 100% sensitive and 60% specific for VAP in those patients who developed clinical signs and symptoms compatible with pneumonia. The pretest and posttest probabilities were 0.38 and 0.6, respectively. Conclusions Sonographic patterns of abnormal aeration are frequently observed in mechanically ventilated patients. If sonographic lung consolidation with either static or dynamic air bronchograms is absent, VAP is highly unlikely. The presence of these sonographic patterns in patients with signs and symptoms suggestive of pneumonia significantly increases the probability of VAP.

New multimodality treatment approaches for prostate cancer require multidisciplinary management of patients. We aimed to assess the current practices of multidisciplinarity and their possible implications in treatment management in Switzerland.In a survey, urologists and medical oncologists in Switzerland were asked to include at least 25 or 15 consecutive patients with the diagnosis of prostate cancer, respectively. Information about treatment patterns and multidisciplinary parameters of these patients was collected retrospectively.Thirty-seven urologists and 20 oncologists from the French- and German-speaking parts of Switzerland representing 7 out of 11 non-university tertiary centres and 20/10 % of all office-based urologists/oncologists in Switzerland collected data on 1,184 patients. Sixty-five percent of the office-based (16/24 urologists; 6/10 oncologists) and 95 % of the hospital-based (10/11 urologists; 8/8 oncologists) physicians participate in multidisciplinary tumour boards (MTBs). However, only 1.5 % of patients with a new diagnosis of prostate cancer (13 of 883) are discussed at a MTB. Overall, second opinions at diagnosis are requested in 23 % of patients, mainly from radiation oncologists (8.4 %) or fellow urologists (7.4 %). Second opinions are more often requested by urologists who participate at MTBs and in case of advanced stage.Participation at MTBs is high among Swiss urologists and oncologists in private practice and at non-university tertiary centers. In spite of that only a small minority of patietns with prostate cancer are presented at MTBs.

Introduction Clinical practice guidelines regarding follow-up in patients after curative resection of colorectal cancer (CRC) vary widely. Current follow-up recommendations do not include additional postoperative imaging before starting adjuvant treatment in any patients. We evaluated the potential benefit of our institutional approach, recommending 18fluor-deoxy-glucose (FDG)-positron emission tomography (PET)-computed tomography (CT) imaging in CRC stage III patients with ≥4 locoregional lymph node metastases (pN2). Patients and Methods Our study included all patients from a single center with complete resection of a pT1-4, pN2, cM0 CRC. All patients were considered free of distant metastases on the basis of preoperative CT imaging of the chest, abdomen, and pelvis. The main objective of the present study was to assess the proportion of patients with changes of therapeutic management (defined as any other treatment than the preplanned adjuvant chemotherapy) because of the results of additional postoperative FDG-PET-CT imaging. Results Fifty patients (22 female/28 male) were included; the median age was 64 years (range, 37-78 years). Previously undiagnosed metastatic disease resulting in a change of the therapeutic management was detected using postoperative FDG-PET-CT imaging in 7 patients (14.0%; 95% confidence interval, 5.8%-26.7%). The number needed to screen to detect new or previously occult metastases was 7 (7 of 50). Conclusion To our knowledge, this is the first study to evaluate the role of an additional postoperative FDG-PET-CT scan before adjuvant treatment in patients with completely resected CRC with ≥4 lymph node metastases (pT1-4, pN2) and without distant metastases on preoperative CT imaging (cM0). Postoperative FDG-PET-CT imaging represents a valuable tool for the detection of new macrometastases in the subgroup of pN2 cM0 CRC patients. The low number needed to screen for consequent therapeutic changes is clinically relevant and should be further evaluated.

2565Background: Estimation of glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing. However, the most accurate method to estimate GFR in patients with cancer is unknown...

We have analysed the influence of acute alcohol exposure in vivo and in vitro on blood flow properties and platelet function. 12 healthy male volunteers drank either 4.36 ml red wine/kg body weight (=0.5 g ethanol/kg) or water at 06.00 p.m. under fasting conditions. Blood was drawn immediately before, and 1, 2, 4 and 13 h after alcohol ingestion. Alcohol had a detectable osmotic effect on erythrocytes; the mean cellular volume (MCV) was significantly smaller 1-4 h after ingestion. Whole blood viscosity remained unaffected, but blood viscosity at a standardized Hct of 45% measured at a high shear rate (94.5 s(-1)) was increased 2 h after wine ingestion. In the morning, 13 h after wine drinking, platelet aggregation measured with a platelet function analyser PFA-100 was increased to a greater extent than after water drinking. In vitro, no effect was seen when blood was incubated with 0, 12.5, 25, 50 and 100 mmol/l ethanol for 1 h at 37 degrees C. We conclude that an acute exposure to alcohol has only modest effects on hemorheological parameters and platelet aggregation in vivo and no effect in vitro, which suggests that other factors must be involved in both beneficial and harmful effects of wine drinking.

This study investigates the announcement and issuance effects of offering convertible bonds and exchangeable bonds using data for the Swiss and German markets during January 1996 and May 2003. The analysis suggests that announcement effects of convertible bonds and exchangeable bonds are associated with significantly negative abnormal returns. German firms exhibit a stronger reaction than Swiss firms, possibly for institutional reasons.We also investigate the effect of the market return of the announcement effect and find that the negative abnormal returns are significantly more pronounced when previous market returns have been negative. Furthermore, we analyze the relation between the announcement effects and equity components by controlling for the equity signal sent to the market. We find the size of the equity component of an issue to have a strong influence on the announcement effect for convertible but not for exchangeable securities and offer an explanation for this difference. http://www.manuel-ammann.com/pdf/CBExBAnnouncements.pdf

Background: Infiltration of non-haematopoietic organs by small lymphocytic lymphoma/chronic lymphocytic leukaemia (SLL/CLL) is not unusual in late-stage disease and thus quite frequently encountered in post-mortem examinations. However, primary manifestation of SLL/CLL in the prostate is rarely diagnosed. Patients and Methods: We report two cases of primary prostatic SLL/CLL, in one case in combination with prostate carcinoma, and discuss diagnostic pitfalls, pathophysiological mechanisms and therapeutic management, together with an overview of the literature. Conclusions: Lymphocytic infiltration of the prostate associated with obstructive symptoms is rare but can already occur in very early disease. Microscopically, SLL/CLL infiltration can be distinguished from chronic prostatitis by its pattern of infiltration and by immunohistochemistry. As the incidence of both SLL/CLL and prostatic carcinoma increases with age, composite tumours might occur more often in the future.

Acetylsalicylic acid (aspirin) is often given together with other nonsteroidal anti-inflammatory drugs and acetaminophen. The latter have been accused in epidemiologic studies to cause an increased cardiovascular risk. We have, therefore, analysed the influence of various such drug combinations on platelet aggregation in vitro. Citrated blood was incubated with either 25 microg/ml acetaminophen, 0.5 microg/ml aspirin, 0.04 microg/ml diclofenac, or buffer; followed by a second of the above-mentioned solutions. After a 20 min incubation, platelet aggregation was assessed with a platelet function analyser (PFA-100), which measures the pore closure time (CT) by aggregating platelets. The length of CT reflects the degree of platelet inhibition. Acetaminophen alone did not affect platelet aggregation. Aspirin and diclofenac both increased CT (184+/-69 s, P

Background The purpose of this study was to survey the current practice of the use of lung ultrasonography (LUS) in the diagnosis of pneumothorax. Methods Physician sonographers, accredited for diagnostic ultrasonography in surgery, anaesthesia and medicine were studied. Questions addressed the frequency of exposure to patients with suspected pneumothorax, frequency of LUS use, preferences regarding technical aspects of LUS examination, assessment of diagnostic accuracy of LUS and involvement in teaching. Results Of the respondents, 55.1% used LUS ‘always’ or ‘frequently’ for suspected pneumothorax. Also, 35.5% of physicians rated LUS as ‘always reliable’ in ruling out pneumothorax, and 21.3% of respondents rated LUS as ‘always reliable’ in ruling in pneumothorax. The mode of performing LUS for pneumothorax was highly variable. Statistically significant differences were found regarding the likelihood of LUS usage, the combined use of M-Mode and B-mode scanning and the confidence to exclude pneumothorax based on LUS findings for physicians with frequent exposure to pneumothorax cases. Conclusions Physicians' use of LUS in the diagnosis of pneumothorax is modest. Confidence in diagnostic accuracy is not comprehensive. Further research is required to establish the most efficient way of performing LUS in this scenario to achieve the highest possible diagnostic accuracy and reliable documentation of examination results.

The purpose of this study was to survey current practice for the use of lung ultrasound (LUS) in the diagnosis of pneumothorax.

Background: Spontaneous pneumothorax (SP) associated with malignant disease is relatively infrequent but has important diagnostic and therapeutic implications. Case Report: We describe a case of SP that occurred during chemotherapy with ifosfamide and doxorubicin in a patient with an advanced pleomorphic sarcoma. The pneumothorax developed secondary to the rapid regression of peripheral pulmonary metastases presumably resulting in bronchopleural fistula formation. After treatment with chest tube drainage, the patient recovered and chemotherapy could be continued without further complications. Discussion: We discuss different pathophysiological mechanisms and the clinical context of SP in sarcoma patients and give an overview of the literature and different treatment options.

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36-year-old male patient presented with rapidly progressive dyspnea over 3 weeks. Computed tomography scan showed a tumor in the right atrium, multiple bilateral pulmonary nodules, and ground-glass infiltrates. Histology obtained by wedge resection of a lung nodule revealed a high-grade epithelial angiosarcoma. Therefore, the patient was diagnosed with angiosarcoma from the right atrium with multiple lung metastases. During the 2 weeks of diagnostic workup, the dyspnea had worsened to New York Heart Association grade IV, and a repeated computed tomography scan showed rapidly progressing pulmonary metastases and infiltrates (Figure 1A). The decision was taken to quickly initiate chemotherapy with doxorubicin (75 mg/m 2 ) and ifosfamide (7500 mg/m 2 ) every 3 weeks. After two cycles of chemotherapy treatment, the patient’s overall condition had markedly improved, and the dyspnea was reduced to New York Heart Association grade I. A partial remission was achieved after six cycles of combination chemotherapy (Figure 1B). Four months later, progression of the primary tumor in the right atrium was diagnosed as well as slightly progressive pulmonary metastases. To avoid the danger of complete obstruction of the right atrium (Figure 2A), we decided to treat the patient with a combination of radiotherapy (22 fractions of 2 Gy) to the right atrium and weekly paclitaxel (80 mg/m 2 weekly). The local response to treatment was good with a marked reduction of the atrial tumor mass (Figure 2B). A few months later, however, there was new evidence of liver metastases. At that point, the patient refused any further treatment. He died 12 months after the initial diagnosis due to an acute intraabdominal hemorrhage most likely deriving from the rapidly progressive liver metastases. DISCUSSION Primary cardiac angiosarcoma (PCA) is an uncommon diagnosis although it is the most frequent primary malignant tumor of the heart. Seventy-five percent of PCA occur in the right heart, especially the right atrium. 1 Complete resection of localized tumors is the treatment of choice in PCA, and there are anecdotal reports of long