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ABSTRACT: To compare tube current adaptation based on 3 body mass index (BMI) categories versus anterior-posterior chest diameter (APD) for radiation dose optimisation in patients undergoing dynamic volume cardiac CT. Two cardiac imaging centres participated in the study. 20 patients underwent a prospectively triggered 320-slice single beat cardiac CT using the X-ray tube current [mA] manually adjusted to the patient's BMI (group I). In 20 subsequent patients, the tube current was adapted according to the patient's APD (group II). All other parameters were kept constant. Image noise was defined as the standard deviation of attenuation values and measured using a ROI in the descending aorta. Variation in image noise was statistically compared between both patient groups. Average and standard deviation of pixel noise were 29.1 HU and 14.8 HU in group I and 28.0 HU and 4.2 HU in group II. Inter-individual variation of pixel noise was significantly lower in group II compared to group I (p < 0.0001). Tube current adaptation based on APD is superior to stepwise adaptation based on BMI for optimising radiation dose in dynamic volume cardiac CT and therefore limits unnecessary radiation dose while ensuring diagnostic image quality in patients with diverse body habitus.
The international journal of cardiovascular imaging 12/2010; 26(8):933-40. · 2.15 Impact Factor
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Manfred Johannsen,
Gianluca Spitaleri,
Giuseppe Curigliano,
Jan Roigas,
Steffen Weikert,
Carsten Kempkensteffen,
Andreas Roemer, Christian Kloeters,
Patrik Rogalla,
Gabriele Pecher, [......],
Alexander Berndt,
Hartwig Kosmehl,
Eveline Trachsel,
Manuela Kaspar,
Valeria Lovato,
Reinerio González-Iglesias,
Leonardo Giovannoni,
Hans D Menssen,
Dario Neri,
Filippo de Braud
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ABSTRACT: L19-IL2, a tumour-targeting immunocytokine composed of the recombinant human antibody fragment L19 (specific to the alternatively-spliced EDB domain of fibronectin, a well characterised marker of tumour neo-vasculature) and of human IL2, has demonstrated strong therapeutic activity in animal cancer models. This phase I/II trial was performed to evaluate safety, tolerability, recommended phase II dose (RD) and early signs of activity of L19-IL2.
Five cohorts of patients with progressive solid tumours (n=21) received an intravenous infusion of L19-IL2 (from 5 to 30 Mio IU IL2 equivalent dose) on days 1, 3 and 5 every 3 weeks. This treatment cycle was repeated up to six times. In the following expansion phase, patients with metastatic renal cell carcinoma (RCC) (n=12) were treated at the RD of L19-IL2. Clinical data and laboratory findings were analysed for safety, tolerability and activity.
Preclinical studies in rats and monkeys did not raise any safety concerns. The RD was defined to be 22.5 Mio IU IL2 equivalent. Pharmacokinetics of L19-IL2 was dose proportional over the tested range, with a terminal half-life of 2-3h. Toxicities were manageable and reversible with no treatment-related deaths. We observed stable disease in 17/33 patients (51%) and 15/18 with mRCC (83%) after two cycles. Median progression-free survival of RCC patients in the expansion phase of the study was 8 months (1.5-30.5).
L19-IL2 can be safely and repeatedly administered at the RD of 22.5 Mio IU IL2 equivalent in advanced solid tumours. Preliminary evaluation suggests clinical activity of L19-IL2 in patients with mRCC.
European journal of cancer (Oxford, England: 1990) 11/2010; 46(16):2926-35. · 4.12 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate a whole-organ perfusion protocol of the pancreas in patients with primary pancreas carcinoma and to analyse perfusion differences between normal and diseased pancreatic tissue. Thirty patients with primary pancreatic malignancy were imaged on a 320-slice CT unit. Twenty-nine cancers were histologically proven. CT data acquisition was started manually after contrast-material injection (8 ml/s, 350 mg iodine/ml) and dynamic density measurements in the right ventricle. After image registration, perfusion was determined with the gradient-relationship technique and volume regions-of-interest were defined for perfusion measurements. Contrast time-density curves and perfusion maps were generated. Statistical analysis was performed using the Kolmogorov-Smirnov test for analysis of normal distribution and Kruskal-Wallis test (nonparametric ANOVA) with Bonferroni correction for multiple stacked comparisons. In all 30 patients the entire pancreas was imaged, and registration could be completed in all cases. Perfusion of pancreatic carcinomas was significantly lower than of normal pancreatic tissue (P < 0.001) and could be visualized on colored perfusion maps. The 320-slice CT allows complete dynamic visualization of the pancreas and enables calculation of whole-organ perfusion maps. Perfusion imaging carries the potential to improve detection of pancreatic cancers due to the perfusion differences.
European Radiology 06/2009; 19(11):2641-6. · 3.22 Impact Factor
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ABSTRACT: Sixty-four-slice CT typified the dramatic race in technical development in radiology. Featuring high spatial resolution with 0.5-mm thin slices and 0.3-second gantry revolution times, it has become state-of-the-art technology in CT imaging shortly after its clinical introduction. Three-dimensional tube modulation together with adaptive x-ray shutters led to significant dose reduction to the patients while improving image quality because of implementation of optimized reconstruction algorithms. The latest innovations-new detector materials, dual-layer detector, dual-source and dynamic volume CT-represent the pinnacles in CT imaging, pursuing different directions to further clinical applications of CT.
Radiologic Clinics of North America 02/2009; 47(1):1-11. · 2.59 Impact Factor
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Manfred Johannsen,
Anne Flörcken,
Axel Bex,
Jan Roigas,
Marco Cosentino,
Vincenzo Ficarra, Christian Kloeters,
Matthias Rief,
Patrik Rogalla,
Kurt Miller,
Viktor Grünwald
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ABSTRACT: Discontinuation of treatment with tyrosine kinase inhibitors (TKIs) and readministration in case of recurrence could improve quality of life (QoL) and reduce treatment costs for patients with metastatic renal cell carcinoma (mRCC) in which a complete remission (CR) is achieved by medical treatment alone or with additional resection of residual metastases.
To evaluate whether TKIs can be discontinued in these selected patients with mRCC.
A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with TKIs (n=266) in five institutions. Patients with a CR under TKI treatment alone or with additional metastasectomy of residual disease following a partial response (PR), in which TKIs were discontinued, were included in the analysis. Outcome criteria analysed were time to recurrence of previous metastases, occurrence of new metastases, symptomatic progression, improvement of adverse events, and response to reexposure to TKIs.
Sunitinib 50mg/day for 4 wk on and 2 wk off, sorafenib 800mg/day.
Response according to Response Evaluation Criteria in Solid Tumours (RECIST).
We identified 12 cases: 5 CRs with sunitinib, 1 CR with sorafenib, and 6 surgical CRs with sunitinib followed by residual metastasectomy. Side-effects subsided in all patients off treatment. At a median follow-up of 8.5 mo (range: 4-25) from TKI discontinuation, 7 of 12 patients remained without recurrence and 5 had recurrent disease, with new metastases in 3 cases. Median time to progression was 6 mo (range: 3-8). Readministration of TKI was effective in all cases. The study is limited by small numbers and retrospective design.
Discontinuation of TKI in patients with mRCC and CR carries the risk of progression with new metastases and potential complications. Further investigation in a larger cohort of patients is warranted before such an approach can be regarded as safe.
European urology 11/2008; 55(6):1430-8. · 7.67 Impact Factor
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ABSTRACT: Previous investigations have shown the usefulness of electron-beam computed tomography (EBCT) to describe ventricular diastolic function and to detect constrictive filling pattern. We used EBCT to analyze diastolic function in patients who underwent passive epicardial constraint because data describing ventricular filling in these patients are still incomplete.
Ten patients with dilated cardiomyopathy (group 1) underwent EBCT examination before and again 6 months after surgery. Ten patients with normal diastolic function (group 2) and 5 male patients with constrictive pericarditis (group 3) served for comparison. Volume-time curves throughout the entire diastole were generated, and the rapidity of diastolic filling was assessed by calculating the percent filling fraction at consecutive EBCT frames throughout the diastole. Pericardial thickness was measured in a standardized fashion at different locations around both ventricles.
Early left ventricular filling pattern in group 1 did not change postoperatively (filling fraction at third diastolic frame was 50.0 +/- 15.4% and 53.8 +/- 14.4% before and after surgery, respectively) and was not significantly different from group 2 (48.7 +/- 8.5%). In contrast, in group 3, early left ventricular filling was significantly accelerated (71.4 +/- 9.3%) when compared with groups 1 and 2. A similar pattern was observed for the right ventricle. Pericardial thickness between groups 1 (1.22 +/- 4.22 and 1.43 +/- 0.39 mm before and after surgery, respectively) and 2 (1.38 +/- 0.43 mm) did not differ significantly. In contrast, pericardium in group 3 was significantly thickened (4.93 +/- 1.11 mm) when compared with both groups 1 and 2.
The EBCT identified an abnormal accelerated diastolic filling and thickened pericardium in patients with constrictive pericarditis. Conversely, a normal diastolic filling pattern and pericardial thickness seem to be preserved in patients after passive epicardial constraint, when compared with baseline values and with normal subjects.
Journal of Computer Assisted Tomography 12/2007; 32(1):78-85. · 1.22 Impact Factor
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ABSTRACT: Previous studies have shown that passive epicardial constraint using a cardiac support device (CSD) reduces left ventricular (LV) size. However, specific data describing LV shape and the time course of changes in LV geometry are still incomplete. Thus, the aim of this study was-using 3-dimensional data sets obtained by computed tomography (CT)-to test the hypothesis that the CSD not only alters LV size but also LV shape, and that short-term post-operative changes in LV geometry are maintained during long-term follow-up.
Ten patients with non-ischemic dilated cardiomyopathy underwent electron-beam CT examination before and again at 2.6 +/- 0.5 and 32.4 +/- 8.7 months after CSD implantation. At end-diastole and end-systole LV volumes, the length-to-width diameter ratio and a sphericity index were determined and ejection fraction and end-systolic meridional and circumferential wall stress were calculated.
Implantation of the CSD led to a significant reduction in LV size, a more ellipsoidal LV shape and a subsequent decrease of LV wall stress post-operatively (p < 0.05 for each), but no substantial changes were found between short- and long-term follow-up (p > 0.05 each). Mean pre-operative and early and late post-operative end-diastolic values were 310.4 +/- 87.8, 235.5 +/- 102.0 and 229.4 +/- 103.1 ml for volume; 1.27 +/- 0.20, 1.37 +/- 0.20 and 1.38 +/- 0.20 for diameter ratio; and 0.78 +/- 0.22, 0.67 +/- 0.26 and 0.65 +/- 0.23 for sphericity index. A similar pattern was observed for end-systolic values. Ejection fraction was 23.4 +/- 6.2%, 32.9 +/- 11.6% and 34.4 +/- 14.9%. End-systolic meridional and circumferential wall stress was 182.2 +/- 45.6, 128.2 +/- 52.6, 130.6 +/- 56.7 kdyn/cm(2) and 411.5 +/- 94.0, 297.4 +/- 108.4 and 302.8 +/- 117.5 kdyn/cm(2), respectively.
Three-dimensional data obtained by CT demonstrate that passive cardiac constraint leads not only to a size reduction but also to an ellipsoidal re-shaping. Our data indicate that these effects are primarily a short-term consequence of the CSD implantation but are maintained during long-term follow-up.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 01/2006; 25(1):90-8. · 3.54 Impact Factor
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ABSTRACT: Previous studies have shown that the cardiac support device (CSD) improves left ventricular structure and function in patients with heart failure by preventing further cardiac enlargement. The aim of this study was to identify effects on the right ventricle (RV).
Ten male patients with idiopathic dilated cardiomyopathy underwent electron-beam computed tomographic (CT) examination within 1 month before, and 6 to 9 months after CSD implantation. The RV end-diastolic and end-systolic volumes (EDV, ESV) and diameters (EDD, ESD), stroke volume (SV), ejection fraction (EF), total and forward RV output (RVO, fRVO), and tricuspid regurgitation fraction (TRF) were calculated.
The EDV measurements decreased from 182.1 +/- 49.6 to 137.5 +/- 37.0 mL, ESV from 114.8 +/- 47.0 to 68.3 +/- 23.8 mL, EDD from 48.2 +/- 6.6 to 41.6 +/- 7.1 mm, and ESD from 39.6 +/- 6.9 to 32.7 +/- 6.5 mm (p < 0.05 for each). Ejection fraction increased from 38.5 +/- 8.9 to 52.0% +/- 7.7% and fRVO from 4.0 +/- 0.8 to 4.6 +/- 1.1 L/min (each with p < 0.05). TRF decreased from 18.2 +/- 14.1 to 10.4% +/- 13.5%, whereas SV and RVO remained nearly unchanged. Postoperatively, RV volumes, EF, and fRVO were not different from 15 age- and gender-matched normal control patients.
Implantation of a CSD leads to a decrease in RV size and improved RV performance. These data together with the results of previous studies demonstrating improved left ventricular structure and function confirm the biventricular nature of recovery with the CSD.
The Annals of thoracic surgery 10/2004; 78(3):900-5. · 3.74 Impact Factor
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ABSTRACT: To verify changes in left ventricular (LV) volumes and regional myocardial wall motion after implantation of a textile cardiac support device (CSD) for passive external constraint in non-ischemic dilated cardiomyopathy.
In nine male patients participating in a non-randomized clinical trial LV volumes were determined and the segmental LV wall motion was studied by contrast-enhanced electron-beam CT in a sectionwise manner at three ventricular levels (base, middle and apex of ventricle) before and 32+/-6 months after CSD implantation. In 16 myocardial segments ejection fraction and wall thickening were measured semiautomatically after drawing the myocardial contours. The wall motion score index was calculated based on semiquantitative visual grading in each segment.
The global LV volumes decreased significantly from 304.3 +/- 90.9 to 231.5 +/- 103.9 ml at end-diastole and from 239.7 +/- 83.7 to 164.0 +/- 97.7 at end-systole (P<0.05). Overall ejection fraction increased from 14.8 +/- 8.2 to 25.7 +/- 17.1% (P<0.05). A segment-by-segment analysis demonstrated a significant increase of regional ejection fraction in the basal myocardium as well as in the mid-inferior, mid-inferolateral, and mid-anterolateral myocardium. Overall wall thickening increased from 16.4 +/- 13.3 to 24.2 +/- 18.1% (P<0.05), but without significant differences in a segment-by-segment comparison. The mean wall motion score index improved from 2.70 +/- 0.26 to 2.20 +/- 0.71 (P<0.05), with an increased wall motion in eight (89%) patients. A section-by-section analysis demonstrated significantly improved wall motion in the inferior and lateral segments at each ventricular level. Postoperatively, the number of akinetic and markedly hypokinetic segments decreased significantly (P<0.05) from 56 (39%) to 26 (18%) and from 76 (53%) to 56 (37%), respectively.
CSD implantation improves segmental wall motion, predominantly in the inferior and lateral myocardium, and reduces the number of akinetic and hypokinetic segments.
European Journal of Cardio-Thoracic Surgery 02/2004; 25(1):84-90. · 2.55 Impact Factor
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Manfred Johannsen,
Anne Flö Rcken,
Axel Bex,
Jan Roigas,
Marco Cosentino,
Vincenzo Ficarra, Christian Kloeters,
Matthias Rief,
Patrik Rogalla,
Kurt Miller,
Viktor Grü Nwald
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ABSTRACT: o p e a n u r o l o g y 5 5 (2 0 0 9) 1 4 3 0 – 1 4 3 9 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Abstract Background: Discontinuation of treatment with tyrosine kinase inhibitors (TKIs) and readminis-tration in case of recurrence could improve quality of life (QoL) and reduce treatment costs for patients with metastatic renal cell carcinoma (mRCC) in which a complete remission (CR) is achieved by medical treatment alone or with additional resection of residual metastases. Objective: To evaluate whether TKIs can be discontinued in these selected patients with mRCC. Design, setting, and participants: A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with TKIs (n = 266) in five institutions. Patients with a CR under TKI treatment alone or with additional metastasectomy of residual disease following a partial response (PR), in which TKIs were discontinued, were included in the analysis. Outcome criteria analysed were time to recurrence of previous metastases, occurrence of new metastases, symptom-atic progression, improvement of adverse events, and response to reexposure to TKIs. Interventions: Sunitinib 50 mg/day for 4 wk on and 2 wk off, sorafenib 800 mg/day. Measurements: Response according to Response Evaluation Criteria in Solid Tumours (RECIST). Results and limitations: We identified 12 cases: 5 CRs with sunitinib, 1 CR with sorafenib, and 6 surgical CRs with sunitinib followed by residual metastasectomy. Side-effects subsided in all patients off treatment. At a median follow-up of 8.5 mo (range: 4–25) from TKI discontinuation, 7 of 12 patients remained without recurrence and 5 had recurrent disease, with new metastases in 3 cases. Median time to progression was 6 mo (range: 3–8). Readministration of TKI was effective in all cases. The study is limited by small numbers and retrospective design. Conclusions: Discontinuation of TKI in patients with mRCC and CR carries the risk of progression with new metastases and potential complications. Further investigation in a larger cohort of patients is warranted before such an approach can be regarded as safe.
