The Impact on Outcome by Adding Bevacizumab to Standard Induction Chemotherapy Prior to Mesothelioma Surgery: A Retrospective Single Center Analysis.

OBJECTIVES: Adding bevacizumab, an anti-Vascular Endothelial Growth Factor (VEGF), to platinum-based chemotherapy/pemetrexed in 1st line treatment of advanced malignant pleural mesothelioma (MPM), significantly improved overall survival. However, increased high grade bleeding after operation was reported in patients with colorectal cancer who previously received bevacizumab. In the present analysis, we assessed for the first time the impact of adding bevacizumab to induction chemotherapy prior to surgery for mesothelioma patients. METHODS: Two hundred twenty-seven MPM patients, intended to be treated with induction chemotherapy followed by surgery at the University Hospital of Zurich between 2002 and December 2018, were included in the present analysis. After propensity score matching for gender, histology and age (1:3 ratio), data from 88 patients were analyzed. Sixty-six patients underwent induction chemotherapy (with cis-/carboplatin and pemetrexed: control group) alone and 22 patients underwent induction chemotherapy with the addition of bevacizumab (bevacizumab group) prior macroscopic complete resection (MCR). Perioperative and long-term outcome variables were analyzed. RESULTS: Patients undergoing combination treatment with bevacizumab had a significantly better response than with chemotherapy alone as assessed by modified RECIST (p=0.046). Intraoperative complications in the bevacizumab group (one patient), or in the control group (three patients) were not related to intraoperative bleeding. Postoperative transfusion of blood products occurred in a larger amount in the control group than in the bevacizumab group (p=0.047). Overall survival was not statistically different between both groups. CONCLUSION: These initial data demonstrate that MCR can be performed safely after triple induction chemotherapy with bevacizumab without increased intra- and postoperative bleeding complications. Response rates were significantly improved by the addition of bevacizumab.

Safety and efficacy of cardiopoietic stem cells in the treatment of post-infarction left-ventricular dysfunction - From cardioprotection to functional repair in a translational pig infarction model.

To date, clinical success of cardiac cell-therapies remains limited. To enhance the cardioreparative properties of stem cells, the concept of lineage-specification through cardiopoietic-guidance has been recently suggested. However, so far, only results from murine studies and from a clinical pilot-trial in chronic heart-failure (CHF) are available, while systematic evidence of its therapeutic-efficacy is still lacking. Importantly, also no data from large animals or for other indications are available. Therefore, we here investigate the therapeutic-efficacy of human cardiopoietic stem cells in the treatment of post-infarction LV-dysfunction using a translational pig-model. Using growth-factor priming, lineage-specification of human bone-marrow derived MSCs was achieved to generate cardiopoietic stem cells according to GMP-compliant protocols. Thereafter, pigs with post-infarction LV-dysfunction (sub-acute phase;1-month) were randomized to either receive transcatheter NOGA 3D electromechanical-mapping guided intramyocardial transplantation of cardiopoietic cells or saline (control). After 30days, cardiac MRI (cMRI) was performed for functional evaluation and in-vivo cell-tracking. This approach was coupled with a comprehensive post-mortem cell-fate and mode-of-repair analysis. Cardiopoietic cell therapy was safe and ejection-fraction was significantly higher when compared to controls (p = 0.012). It further prevented maladaptive LV-remodeling and revealed a significantly lower relative and total infarct-size (p = 0.043 and p = 0.012). As in-vivo tracking and post-mortem analysis displayed only limited intramyocardial cardiopoietic cell-integration, the significant induction of neo-angiogenesis (∼40% higher; p = 0.003) and recruitment of endogenous progenitors (∼2.5x higher; p = 0.008) to the infarct border-zone appeared to be the major modes-of-repair. This is the first report using a pre-clinical large animal-model to demonstrate the safety and efficacy of cardiopoietic stem cells for the treatment of post-infarction LV-dysfunction to prevent negative LV-remodeling and subsequent CHF. It further provides insight into post-delivery cardiopoietic cell-fate and suggests the mechanisms of cardiopoietic cell-induced cardiac-repair. The adoption of GMP-/GLP-compliant methodologies may accelerate the translation into a phase-I clinical-trial in patients with post-ischemic LV-dysfunction broadening the current indication of this interesting cell-type.

Long-term results of simplified frozen elephant trunk technique in complicated acute type A aortic dissection: A case-control study.

AIM: To describe the long-term experience of a simplified frozen elephant trunk technique (sFETT) used in complicated acute type A aortic dissection (AAAD) treatment. METHODS AND RESULTS: Between January 2001 and December 2012, 34 patients (mean age 59.9 ± 11.0 years) with complicated AAAD (DeBakey I) underwent an emergency surgery including sFETT. sFETT consisted in gluing the dissected aortic arch wall layers with gelatine-resorcinol adhesive and video-assisted antegrade open arch aortic stent-graft deployment in the arch or proximal descending aorta. In addition to sFETT, the aortic root was addressed with standard techniques. A 30-day mortality was 14.7% (five patients) due to bleeding (1), multiple organ failure (2), and colon ischemia (2). Postoperative morbidity included neurological (2), renal (1) and cardio-pulmonary complications (4), as well as wound infection (1). Mean follow-up was 74.4 ± 45.0 months. Actual survival rates were 73.5% at 1 year, 70.2% at 5 years, and 58.5% at 13 years of follow-up. Six patients died during long-term follow-up from heart failure (1) and unknown reasons (5). Five patients required reoperation for aortic arch (3) or aorto-iliac (2) progression of aneurysm during the mid- and long-term follow-up. The remaining patients showed favorable evolution of the dissected aorta with false lumen occlusion in most cases and stable aortic diameters. CONCLUSIONS: In AAAD patients, sFETT as used in our series is an easy and safe technique to repair the aortic arch. Long-term results after sFETT showed false lumen occlusion and stable aortic diameter in up to 13 years of follow-up.

Influence of Sinogram-Affirmed Iterative Reconstruction on Computed Tomography-Based Lung Volumetry and Quantification of Pulmonary Emphysema.

OBJECTIVE: The purpose of this study was to evaluate the influence of sinogram-affirmed iterative reconstruction (SAFIRE) on quantification of lung volume and pulmonary emphysema in low-dose chest computed tomography compared with filtered back projection (FBP). METHODS: Enhanced or nonenhanced low-dose chest computed tomography was performed in 20 patients with chronic obstructive pulmonary disease (group A) and in 20 patients without lung disease (group B). Data sets were reconstructed with FBP and SAFIRE strength levels 3 to 5. Two readers semiautomatically evaluated lung volumes and automatically quantified pulmonary emphysema, and another assessed image quality. Radiation dose parameters were recorded. RESULTS: Lung volume between FBP and SAFIRE 3 to 5 was not significantly different among both groups (all P > 0.05). When compared with those of FBP, total emphysema volume was significantly lower among reconstructions with SAFIRE 4 and 5 (mean difference, 0.56 and 0.79 L; all P < 0.001). There was no nondiagnostic image quality. CONCLUSIONS: Sinogram-affirmed iterative reconstruction does not alter lung volume measurements, although quantification of lung emphysema is affected at higher strength levels.

Use of computed tomography and positron emission tomography/computed tomography for staging of local extent in patients with malignant pleural mesothelioma.

PURPOSE: The objective of this study was to determine the diagnostic value of computed tomography (CT) and positron emission tomography (PET)/CT for staging of malignant pleural mesothelioma (MPM) in patients undergoing induction chemotherapy. METHODS: Sixty-two patients (median age, 61 years; female: n = 9) with proven MPM underwent CT after induction chemotherapy. Of these, 28 underwent additional PET/CT. Extrapleural pneumonectomy was performed for pathological TNM staging. Clinical TNM stage was assessed by 3 independent readers. Relative and absolute underestimation and overestimation were compared with pathological tumor stage. Sensitivity, specificity, and accuracy for differentiation between stages T2 and T3 were assessed. Interobserver agreement between the readers was analyzed (κ). RESULTS: Positron emission tomography/CT and CT underestimated T stage in up to 30% of the cases. Positron emission tomography/CT had a higher accuracy for tumor extent compared with CT (PET/CT: 0.92; CT: 0.84). The accuracy for nodal staging was higher for CT than for PET/CT (PET/CT: 0.78; CT: 0.87). Concerning International Mesothelioma Interest Group classification, PET/CT improved the accuracy of preoperative staging compared with CT (PET/CT: 0.91; CT: 0.82). Interobserver agreement was moderate for CT (0.48-0.62) and good for PET/CT (0.64-0.83) for T staging. For nodal staging, interobserver agreement was fair to moderate for CT and good for PET/CT (CT: 0.37-0.51; PET/CT: 0.73-0.76). CONCLUSIONS: Positron emission tomography/CT is more accurate and has a lower interobserver variability for clinical intrathoracic staging of MPM compared with CT. Nevertheless PET/CT underestimated tumor stage in a substantial number of cases, showing the need for a more accurate imaging technology or approach.

Screening for interstitial lung disease in systemic sclerosis: performance of high-resolution CT with limited number of slices: a prospective study.

OBJECTIVES: Early diagnosis of interstitial lung disease (ILD), currently the main cause of death in systemic sclerosis (SSc), is needed. The gold standard is high-resolution CT (HRCT) of the chest, but regular screening faces the risk of increased radiation exposure. We performed a prospective validation of a dedicated, 9-slice HRCT protocol with reduced radiation dose for the detection of ILD in patients with SSc. METHODS: We analysed 170/205 consecutive patients with SSc. Whole-chest HRCT, serving as standard of reference, and the reduced HRCT with nine slices allocated according to a basal-apical gradient were obtained. ILD presence, extent (> or <20%) and diagnostic confidence were assessed. The reduced HRCT was independently analysed by two blinded radiologists, who also evaluated image quality. Radiation dose parameters were calculated. RESULTS: Standard chest HRCT showed ILD in 77/170 patients. With the reduced HRCT, 68/77 cases with ILD were identified (sensitivity 88.3%, both readers). The accuracy (91.8%, reader 1; 94.7%, reader 2), diagnostic confidence (98.8%, reader 1; 95.3%, reader 2) and image quality rates were high. Minimal ILD was correctly quantified in 73.1% (reader 1)/71.2% (reader 2) and extensive ILD in 88% (reader 1)/100% (reader 2). Importantly, the reduced HRCT had a significantly lower radiation dose. The mean dose length product (effective dose) was only 5.66±4.46 mGycm (0.08±0.06 mSv) compared with the standard protocol dose of 149.00±95.90 mGycm (2.09±1.34 mSv). CONCLUSIONS: The above-described reduced chest HRCT protocol reliably detects even mild SSc-ILD in clinical practice, with the advantage of a much lower radiation dose compared with standard whole-chest HRCT.

Impact of three-dimensional imaging and pressure recovery on echocardiographic evaluation of severe aortic stenosis: a pilot study.

AIMS: In patients with aortic stenosis (AS), echocardiographic grading of stenosis severity is important, in particular for transcatheter aortic valve implantation (TAVI). Three-dimensional (3D) echocardiography and correction for pressure recovery (PR) by energy loss index (ELI) may improve aortic valve area (AVA) calculation. METHODS AND RESULTS: Thirty-nine patients with severe AS evaluated for TAVI were included. Left ventricular outflow tract (LVOT) and ascending aorta (AA) cross-sectional area were determined in transthoracic two-dimensional echocardiography (2DTTE), 2D transesophageal echocardiography (TEE), 3DTEE, and multislice computed tomography (MSCT). AVA was calculated by the continuity equation and corrected for PR. ELI was determined as [(AVA × AA)/(AA - AVA)]/body surface area. LVOT area was 2.41 ± 0.17 cm(2) calculated using 2DTTE, 2.82 ± 0.16 cm(2) calculated using 2DTEE, 3.96 ± 0.14 cm(2) planimetered in 3DTEE, and 4.47 ± 0.18 cm(2) planimetered in MSCT (P < 0.001). AA area was 4.62 ± 0.23 cm(2) calculated using 2DTTE, 4.64 ± 0.23 cm(2) calculated using 2DTEE, 5.35 ± 0.25 cm(2) planimetered in 3DTEE, and 6.56 ± 0.31 cm(2) planimetered in MSCT (P < 0.001). Indexed aortic valve area (AVAI) calculated by 2DTTE and 2DTEE was smaller (0.27 ± 0.02 cm(2) /m(2) and 0.32 ± 0.02 cm(2) /m(2) ) compared to 3DTEE (0.45 ± 0.02 cm(2) /m(2) ; P < 0.001). When AVAI determined by 3DTEE was corrected for PR by calculation of ELI, there was a further increase (0.52 ± 0.03 cm(2) /m(2) ; P < 0.001), and 10/36 (27.8%) patients were reclassified to moderate AS. CONCLUSION: Three-dimensional TEE is more accurate than 2DTTE and 2DTEE for determining LVOT and AA dimensions. When AS severity is determined by 3DTEE and corrected for PR using the 3D values, it needs to be reclassified from severe to moderate in almost a third of patients.

Maximum diameter measurements of aortic aneurysms on axial CT images after endovascular aneurysm repair: sufficient for follow-up?

PURPOSE: To assess the accuracy of maximum diameter measurements of aortic aneurysms after endovascular aneurysm repair (EVAR) on axial computed tomographic (CT) images in comparison to maximum diameter measurements perpendicular to the intravascular centerline for follow-up by using three-dimensional (3D) volume measurements as the reference standard. MATERIALS AND METHODS: Forty-nine consecutive patients (73 ± 7.5 years, range 51-88 years), who underwent EVAR of an infrarenal aortic aneurysm were retrospectively included. Two blinded readers twice independently measured the maximum aneurysm diameter on axial CT images performed at discharge, and at 1 and 2 years after intervention. The maximum diameter perpendicular to the centerline was automatically measured. Volumes of the aortic aneurysms were calculated by dedicated semiautomated 3D segmentation software (3surgery, 3mensio, the Netherlands). Changes in diameter of 0.5 cm and in volume of 10% were considered clinically significant. Intra- and interobserver agreements were calculated by intraclass correlations (ICC) in a random effects analysis of variance. The two unidimensional measurement methods were correlated to the reference standard. RESULTS: Intra- and interobserver agreements for maximum aneurysm diameter measurements were excellent (ICC = 0.98 and ICC = 0.96, respectively). There was an excellent correlation between maximum aneurysm diameters measured on axial CT images and 3D volume measurements (r = 0.93, P < 0.001) as well as between maximum diameter measurements perpendicular to the centerline and 3D volume measurements (r = 0.93, P < 0.001). CONCLUSION: Measurements of maximum aneurysm diameters on axial CT images are an accurate, reliable, and robust method for follow-up after EVAR and can be used in daily routine.