Publications by authors named "Thi Dan Linh Nguyen-Kim"

41 Publications

Prognostic Value of Deep Learning-Mediated Treatment Monitoring in Lung Cancer Patients Receiving Immunotherapy.

Front Oncol 2021 2;11:609054. Epub 2021 Mar 2.

Department of Radiology, Netherlands Cancer Institute - Antoni vanLeeuwenhoek Hospital, Amsterdam, Netherlands.

Background: Checkpoint inhibitors provided sustained clinical benefit to metastatic lung cancer patients. Nonetheless, prognostic markers in metastatic settings are still under research. Imaging offers distinctive advantages, providing whole-body information non-invasively, while routinely available in most clinics. We hypothesized that more prognostic information can be extracted by employing artificial intelligence (AI) for treatment monitoring, superior to 2D tumor growth criteria.

Methods: A cohort of 152 stage-IV non-small-cell lung cancer patients (NSCLC) (73 discovery, 79 test, 903CTs), who received nivolumab were retrospectively collected. We trained a neural network to identify morphological changes on chest CT acquired during patients' follow-ups. A classifier was employed to link imaging features learned by the network with overall survival.

Results: Our results showed significant performance in the independent test set to predict 1-year overall survival from the date of image acquisition, with an average area under the curve (AUC) of 0.69 ( 0.01), up to AUC 0.75 ( < 0.01) in the first 3 to 5 months of treatment, and 0.67 AUC ( = 0.01) for durable clinical benefit (6 months progression-free survival). We found the AI-derived survival score to be independent of clinical, radiological, PDL1, and histopathological factors. Visual analysis of AI-generated prognostic heatmaps revealed relative prognostic importance of morphological nodal changes in the mediastinum, supraclavicular, and hilar regions, lung and bone metastases, as well as pleural effusions, atelectasis, and consolidations.

Conclusions: Our results demonstrate that deep learning can quantify tumor- and non-tumor-related morphological changes important for prognostication on serial imaging. Further investigation should focus on the implementation of this technique beyond thoracic imaging.
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http://dx.doi.org/10.3389/fonc.2021.609054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962549PMC
March 2021

Combination of HAI-FUDR and Systemic Gemcitabine and Cisplatin in Unresectable Cholangiocarcinoma: A Dose Finding Single Center Study.

Oncology 2021 Mar 3:1-10. Epub 2021 Mar 3.

Department of Medical Oncology and Hematology, Division of Medical Oncology, University Hospital Zurich, Zurich, Switzerland,

Background: Unresectable cholangiocarcinoma has a poor prognosis and treatment options are limited. Combined systemic and intrahepatic chemotherapy may improve local control and enable downsizing. The aim of this study was to determine the maximum tolerated dose (MTD) of intravenous gemcitabine combined with intravenous cisplatin and hepatic arterial infusion (HAI) with floxuridine (FUDR) in patients with unresectable intrahepatic or hilar cholangiocarcinoma.

Methods: Twelve patients were treated within a 3 + 3 dose escalation algorithm with 600, 800, or 1,000 mg/m2 gemcitabine and predefined doses of cisplatin 25 mg/m2 on days 1 and 8, q21, for 4 cycles, and FUDR 0.2 mg/kg on days 1-14 as continuous HAI, q28, for 3 cycles. Safety and toxicity as well as resectability rates after 3 months and preliminary survival data are reported.

Results: The determined MTD for gemcitabine was 800 mg/m2. Dose limiting toxicities were neutropenic fever and biliary tract infections. In total, 27% of the patients showed partial remission and 73% stable disease. Although none of the patients achieved resectability after 3 months, the 3-year overall survival rate was 33%, median overall survival 23.9 months (range 1-49), and median progression-free survival 10.1 months (range 2-40).

Conclusions: Intravenous gemcitabine/cisplatin plus HAI-FUDR is feasible and appears effective for disease control. Larger prospective studies evaluating this triplet combination are warranted.
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http://dx.doi.org/10.1159/000512967DOI Listing
March 2021

Outcome of Patients With Severe Aortic Stenosis and Normal Coronary Arteries Undergoing Transcatheter Aortic Valve Implantation.

Am J Cardiol 2021 03 6;143:89-96. Epub 2021 Jan 6.

Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland. Electronic address:

Coronary artery disease and severe aortic stenosis (AS) often coexist. This study sought to investigate the impact of normal coronary arteries as negative risk marker in patients undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients with severe AS undergoing TAVI were dichotomized according to the presence or absence of normal coronary arteries, defined as absence of coronary lesions with diameter stenosis ≥30% in vessels ≥1.5 mm in diameter on coronary angiogram in patients without prior coronary revascularization. The primary end point was 1-year mortality. Out of 987 patients with severe AS undergoing TAVI, 258 (26%) patients had normal coronary arteries. These patients were younger, more likely women, and had lower EuroSCORE II and STS risk scores. Although mortality at 30 days was similar in the normal coronary artery and the coronary atherosclerosis groups (3.1% vs 5.6%, p = 0.11), it was lower in those with normal coronary arteries at 1 year (8.9% vs 17%, p = 0.003). In multivariable analysis, the presence of normal coronary arteries on coronary angiogram independently predicted 1-year mortality (adjusted HR 0.57, 95% CI 0.37 to 0.90, p = 0.02). In conclusion, this study defined normal coronary arteries as negative risk marker in patients with severe AS undergoing TAVI.
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http://dx.doi.org/10.1016/j.amjcard.2020.12.030DOI Listing
March 2021

Accuracy of Conventional and Machine Learning Enhanced Chest Radiography for the Assessment of COVID-19 Pneumonia: Intra-Individual Comparison with CT.

J Clin Med 2020 Nov 6;9(11). Epub 2020 Nov 6.

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.

Purpose: To evaluate diagnostic accuracy of conventional radiography (CXR) and machine learning enhanced CXR (mlCXR) for the detection and quantification of disease-extent in COVID-19 patients compared to chest-CT.

Methods: Real-time polymerase chain reaction (rt-PCR)-confirmed COVID-19-patients undergoing CXR from March to April 2020 together with COVID-19 negative patients as control group were retrospectively included. Two independent readers assessed CXR and mlCXR images for presence, disease extent and type (consolidation vs. ground-glass opacities (GGOs) of COVID-19-pneumonia. Further, readers had to assign confidence levels to their diagnosis. CT obtained ≤ 36 h from acquisition of CXR served as standard of reference. Inter-reader agreement, sensitivity for detection and disease extent of COVID-19-pneumonia compared to CT was calculated. McNemar test was used to test for significant differences.

Results: Sixty patients (21 females; median age 61 years, range 38-81 years) were included. Inter-reader agreement improved from good to excellent when mlCXR instead of CXR was used (k = 0.831 vs. k = 0.742). Sensitivity for pneumonia detection improved from 79.5% to 92.3%, however, on the cost of specificity 100% vs. 71.4% ( = 0.031). Overall, sensitivity for the detection of consolidation was higher than for GGO (37.5% vs. 70.4%; respectively). No differences could be found in disease extent estimation between mlCXR and CXR, even though the detection of GGO could be improved. Diagnostic confidence was better on mlCXR compared to CXR ( = 0.013).

Conclusion: In line with the current literature, the sensitivity for detection and quantification of COVID-19-pneumonia was moderate with CXR and could be improved when mlCXR was used for image interpretation.
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http://dx.doi.org/10.3390/jcm9113576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694629PMC
November 2020

Patterns of organizing pneumonia and microinfarcts as surrogate for endothelial disruption and microangiopathic thromboembolic events in patients with coronavirus disease 2019.

PLoS One 2020 5;15(10):e0240078. Epub 2020 Oct 5.

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.

Background: To evaluate chest-computed-tomography (CT) scans in coronavirus-disease-2019 (COVID-19) patients for signs of organizing pneumonia (OP) and microinfarction as surrogate for microscopic thromboembolic events.

Methods: Real-time polymerase-chain-reaction (RT-PCR)-confirmed COVID-19 patients undergoing chest-CT (non-enhanced, enhanced, pulmonary-angiography [CT-PA]) from March-April 2020 were retrospectively included (COVID-19-cohort). As control-groups served 175 patients from 2020 (cohort-2020) and 157 patients from 2019 (cohort-2019) undergoing CT-PA for pulmonary embolism (PE) during the respective time frame at our institution. Two independent readers assessed for presence and location of PE in all three cohorts. In COVID-19 patients additionally parenchymal changes typical of COVID-19 pneumonia, infarct pneumonia and OP were assessed. Inter-reader agreement and prevalence of PE in different cohorts were calculated.

Results: From 68 COVID-19 patients (42 female [61.8%], median age 59 years [range 32-89]) undergoing chest-CT 38 obtained CT-PA. Inter-reader-agreement was good (k = 0.781). On CT-PA, 13.2% of COVID-19 patients presented with PE whereas in the control-groups prevalence of PE was 9.1% and 8.9%, respectively (p = 0.452). Up to 50% of COVID-19 patients showed changes typical for OP. 21.1% of COVID-19 patients suspected with PE showed subpleural wedge-shaped consolidation resembling infarct pneumonia, while only 13.2% showed visible filling defects of the pulmonary artery branches on CT-PA.

Conclusion: Despite the reported hypercoagulability in critically ill patients with COVID-19, we did not encounter higher prevalence of PE in our patient cohort compared to the control cohorts. However, patients with suspected PE showed a higher prevalence of lung changes, resembling patterns of infarct pneumonia or OP and CT-signs of pulmonary-artery hypertension.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240078PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535037PMC
October 2020

Multimodality imaging derived energy loss index and outcome after transcatheter aortic valve replacement.

Eur Heart J Cardiovasc Imaging 2020 10;21(10):1092-1102

Department of Cardiology, University Heart Center Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.

Aims: To assess whether the combination of transthoracic echocardiography (TTE) and multidetector computed tomography (MDCT) data affects the grading of aortic stenosis (AS) severity under consideration of the energy loss index (ELI) in patients undergoing transcatheter aortic valve replacement (TAVR).

Methods And Results: Multimodality imaging was performed in 197 patients with symptomatic severe AS undergoing TAVR at the University Hospital Zurich, Switzerland. Fusion aortic valve area index (fusion AVAi) assessed by integrating MDCT derived planimetric left ventricular outflow tract area into the continuity equation was significantly larger as compared to conventional AVAi (0.41 ± 0.1 vs. 0.51 ± 0.1 cm2/m2; P < 0.01). A total of 62 patients (31.4%) were reclassified from severe to moderate AS with fusion AVAi being >0.6 cm2/m2. ELI was obtained for conventional AVAi and fusion AVAi based on sinotubular junction area determined by TTE (ELILTL 0.47 ± 0.1 cm2/m2; fusion ELILTL 0.60 ± 0.1 cm2/m2) and MDCT (ELIMDCT 0.48 ± 0.1 cm2/m2; fusion ELIMDCT 0.61 ± 0.05 cm2/m2). When ELI was calculated with fusion AVAi the effective orifice area was >0.6 cm2/m2 in 85 patients (43.1%). Survival rate 3 years after TAVR was higher in patients reclassified to moderate AS according to multimodality imaging derived ELI (78.8% vs. 67%; P = 0.01).

Conclusion: Multimodality imaging derived ELI reclassifies AS severity in 43% undergoing TAVR and predicts mid-term outcome.
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http://dx.doi.org/10.1093/ehjci/jeaa100DOI Listing
October 2020

Flat chest projection in the detection and visualization of rib fractures: A cross-sectional study comparing curved and multiplanar reformation of computed tomography images in different reader groups.

Forensic Sci Int 2019 Oct 12;303:109942. Epub 2019 Sep 12.

Department of Orthopedics, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008 Zurich, Switzerland. Electronic address:

Background: Rib fractures are common and potentially life-threatening. Fast and correct detection as well as comprehensive visual overview of rib fractures are of clinical and forensic importance. This study compared two computed tomography (CT) reformation methods, curved planar reformation (CPR) with conventional multiplanar reformation (MPR), regarding detection of rib fractures in different readers.

Methods: Twelve postmortem CT datasets were retrospectively assessed for rib fractures using CPR and MPR. After defining the gold-standard regarding side, level, localization, and quantity of fractures, four reader groups per two readers consisting of radiologists, trauma surgeons, forensic pathologists, and laypersons, were evaluated for sensitivity, proportion of false positives, time to fracture detection, and subjective preference.

Results: Overall sensitivity for fracture detection did not vary significantly between both methods. However, it was significantly higher in trauma surgeons and laypersons when reading CPR compared to MPR (70.7% vs. 62.0%, p=0.038 and 33.7% vs. 22.1%, p=0.003 respectively). It was significantly lower in radiologists (63.8% vs. 76.8%, p=0.001). Forensic pathologists performed similarly with both methods (53.6% vs. 56.5%, p=0.549). All non-radiologists preferred the use of CPR (75%). All readers found CPR to provide better visual overview (100%).

Conclusion: CPR may increase rib fracture detection rates of non-radiologists (i.e. trauma surgeons and laypersons) and provides a better visual overview. However, radiologists achieve higher fracture detection rates when allowed to work with the software tools they are more experienced with. The overall sensitivity was improvable and better visualization methods are warranted in order to avoid misdiagnosis and medicolegal errors regarding rib fracture detection.
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http://dx.doi.org/10.1016/j.forsciint.2019.109942DOI Listing
October 2019

Volumetric assessment of solid pulmonary nodules on ultralow-dose CT: a phantom study.

J Thorac Dis 2019 Aug;11(8):3515-3524

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.

Background: To reduce the radiation exposure from chest computed tomography (CT), ultralow-dose CT (ULDCT) protocols performed at sub-millisievert levels were previously tested for the evaluation of pulmonary nodules (PNs). The purpose of our study was to investigate the effect of ULDCT and iterative image reconstruction on volumetric measurements of solid PNs.

Methods: CT datasets of an anthropomorphic chest phantom containing solid microspheres were obtained with a third-generation dual-source CT at standard dose, 1/8th, 1/20th and 1/70th of standard dose [CT volume dose index (CTDI): 0.03-2.03 mGy]. Semi-automated volumetric measurements were performed on CT datasets reconstructed with filtered back projection (FBP) and advanced modelled iterative reconstruction (ADMIRE), at strength level 3 and 5. Absolute percentage error (APE) evaluated measurement accuracy related to the effective volume. Scan repetition differences were evaluated using Bland-Altman analysis. Two-way analysis of variance (ANOVA) assessed influence of different scan parameters on APE. Proportional differences (PDs) tested the effect of dose settings and reconstruction algorithms on volumetric measurements, as compared to the standard protocol (standard dose-FBP).

Results: Bland-Altman analysis revealed small mean interscan differences of APE with narrow limits of agreement (-0.1%±4.3% to -0.3%±3.8%). Dose settings (P<0.001), reconstruction algorithms (P<0.001), nodule diameters (P<0.001) and nodule density (P=0.011) had statistically significant influence on APE. Post-hoc Bonferroni tests showed slightly higher APE when scanning with 1/70th of standard dose [mean difference: 3.4%, 95% confidence interval (CI): 2.5-4.3%; P<0.001], and for image reconstruction with ADMIRE5 (mean difference: 1.8%, 95% CI: 1.0-2.5%; P<0.001). No significant differences for scanning with 1/20th of standard dose (P=0.42), and image reconstruction with ADMIRE3 (P=0.19) were found. Scanning with 1/70th of standard dose and image reconstruction with FBP showed the widest range of PDs (-16.8% to 23.4%) compared to standard dose-FBP.

Conclusions: Our phantom study showed no significant difference between nodule volume measurements on standard dose CT (CTDI: 2 mGy) and ULDCT with 1/20th of standard dose (CTDI: 0.10 mGy).
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http://dx.doi.org/10.21037/jtd.2019.08.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753441PMC
August 2019

Radiogenomics: bridging imaging and genomics.

Abdom Radiol (NY) 2019 06;44(6):1960-1984

Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

From diagnostics to prognosis to response prediction, new applications for radiomics are rapidly being developed. One of the fastest evolving branches involves linking imaging phenotypes to the tumor genetic profile, a field commonly referred to as "radiogenomics." In this review, a general outline of radiogenomic literature concerning prominent mutations across different tumor sites will be provided. The field of radiogenomics originates from image processing techniques developed decades ago; however, many technical and clinical challenges still need to be addressed. Nevertheless, increasingly accurate and robust radiogenomic models are being presented and the future appears to be bright.
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http://dx.doi.org/10.1007/s00261-019-02028-wDOI Listing
June 2019

Peripheral Blood TCR Repertoire Profiling May Facilitate Patient Stratification for Immunotherapy against Melanoma.

Cancer Immunol Res 2019 01 13;7(1):77-85. Epub 2018 Nov 13.

University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Many metastatic melanoma patients experience durable responses to anti-PD1 and/or anti-CTLA4; however, a significant proportion (over 50%) do not benefit from the therapies. In this study, we sought to assess pretreatment liquid biopsies for biomarkers that may correlate with response to checkpoint blockade. We measured the combinatorial diversity evenness of the T-cell receptor (TCR) repertoire (the DE, with low values corresponding to more clonality and lack of TCR diversity) in pretreatment peripheral blood mononuclear cells from melanoma patients treated with anti-CTLA4 ( = 42) or anti-PD1 ( = 38) using a multi-N-plex PCR assay on genomic DNA (gDNA). A receiver operating characteristic curve determined the optimal threshold for a dichotomized analysis according to objective responses as defined by RECIST1.1. Correlations between treatment outcome, clinical variables, and DE were assessed in multivariate regression models and confirmed with Fisher exact tests. In samples obtained prior to treatment initiation, we showed that low DE values were predictive of a longer progression-free survival and good responses to PD-1 blockade, but, on the other hand, predicted a poor response to CTLA4 inhibition. Multivariate logistic regression models identified DE as the only independent predictive factor for response to anti-CTLA4 therapy ( = 0.03) and anti-PD1 therapy ( = 0.001). Fisher exact tests confirmed the association of low DE with response in the anti-CTLA4 ( = 0.041) and the anti-PD1 cohort ( = 0.0016). Thus, the evaluation of basal TCR repertoire diversity in peripheral blood, using a PCR-based method, could help predict responses to anti-PD1 and anti-CTLA4 therapies.
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http://dx.doi.org/10.1158/2326-6066.CIR-18-0136DOI Listing
January 2019

Pre-procedural CT angiography inferior vena cava measurements: a predictor of mortality in patients undergoing transcatheter aortic valve implantation.

Eur Radiol 2019 Feb 17;29(2):975-984. Epub 2018 Jul 17.

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Raemistr. 100, 8091, Zurich, Switzerland.

Objectives: To assess the value of pre-procedural computed tomography angiography (CTA) measurements of the suprahepatic inferior vena cava (IVC) to detect elevated central venous pressure (CVP) assessed by right heart catheterisation (RHC), and to predict post-procedural 1-year mortality in a cohort of patients undergoing transcatheter aortic valve implantation (TAVI).

Methods: We retrospectively evaluated 408 consecutive patients undergoing CTA before TAVI between January 2011 and December 2014. Two hundred and five patients were included in the RHC cohort, who underwent RHC and CTA within ≤1 day prior to TAVI. Two hundred and three patients not fulfilling this requirement were included in the validation cohort. Measurements of the IVC were performed between diaphragm and right atrium on axial slices. Receiver operating characteristic (ROC) analyses, Kaplan-Meier analyses and Cox regression analyses were performed.

Results: In the RHC cohort, ROC curve analyses for IVC area measurements indicated an AUC of 0.77 (p < 0.001) to detect CVP ≥10mmHg and an area under the ROC curve (AUC) of 0.72 (p < 0.001) to predict 1-year mortality. An IVC area cut-off of ≥665 mm predicted 1-year mortality with a specificity of 84% and a sensitivity of 63%. Kaplan-Meier analysis showed that patients with an IVC area ≥665 mm had a significantly higher post-procedural 1-year mortality (38% versus 7%, log-rank p < 0.001) with a hazard ratio of 5.5 (95% CI, 2.2-13.6; p < 0.001). Applying this cut-off value to the validation cohort confirmed a significantly higher 1-year mortality after TAVI (34% versus 11%; log-rank p = 0.004) for patients with an IVC area ≥665 mm.

Conclusions: Pre-procedural enlargement of the suprahepatic IVC is a predictor of post-procedural 1-year mortality in patients evaluated for TAVI.

Key Points: • IVC measurements are moderate predictors of an elevated CVP in TAVI patients. • Pre-procedural IVC enlargement is a predictor of 1-year mortality after TAVI. • IVC enlargement is associated with right heart dysfunction in TAVI patients.
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http://dx.doi.org/10.1007/s00330-018-5613-xDOI Listing
February 2019

The impact of slice-reduced computed tomography on histogram-based densitometry assessment of lung fibrosis in patients with systemic sclerosis.

J Thorac Dis 2018 04;10(4):2142-2152

Institute of Diagnostic and Interventional Radiology, Raemistrasse, Zurich, Switzerland.

Background: To evaluate usability of slice-reduced sequential computed tomography (CT) compared to standard high-resolution CT (HRCT) in patients with systemic sclerosis (SSc) for qualitative and quantitative assessment of interstitial lung disease (ILD) with respect to (I) detection of lung parenchymal abnormalities, (II) qualitative and semiquantitative visual assessment, (III) quantification of ILD by histograms and (IV) accuracy for the 20%-cut off discrimination.

Methods: From standard chest HRCT of 60 SSc patients sequential 9-slice-computed tomography (reduced HRCT) was retrospectively reconstructed. ILD was assessed by visual scoring and quantitative histogram parameters. Results from standard and reduced HRCT were compared using non-parametric tests and analysed by univariate linear regression analyses.

Results: With respect to the detection of parenchymal abnormalities, only the detection of intrapulmonary bronchiectasis was significantly lower in reduced HRCT compared to standard HRCT (P=0.039). No differences were found comparing visual scores for fibrosis severity and extension from standard and reduced HRCT (P=0.051-0.073). All scores correlated significantly (P<0.001) to histogram parameters derived from both, standard and reduced HRCT. Significant higher values of kurtosis and skewness for reduced HRCT were found (both P<0.001). In contrast to standard HRCT histogram parameters from reduced HRCT showed significant discrimination at cut-off 20% fibrosis (sensitivity 88% kurtosis and skewness; specificity 81% kurtosis and 86% skewness; cut-off kurtosis ≤26, cut-off skewness ≤4; both P<0.001).

Conclusions: Reduced HRCT is a robust method to assess lung fibrosis in SSc with minimal radiation dose with no difference in scoring assessment of lung fibrosis severity and extension in comparison to standard HRCT. In contrast to standard HRCT histogram parameters derived from the approach of reduced HRCT could discriminate at a threshold of 20% lung fibrosis with high sensitivity and specificity. Hence it might be used to detect early disease progression of lung fibrosis in context of monitoring and treatment of SSc patients.
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http://dx.doi.org/10.21037/jtd.2018.04.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949494PMC
April 2018

Impact of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) on growth of colorectal liver metastases.

Surgery 2018 02 13;163(2):311-317. Epub 2017 Dec 13.

Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland; Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France. Electronic address:

Background: Associating liver partition and portal vein ligation for staged hepatectomy induces an unprecedented liver hypertrophy and enables resection of otherwise unresectable liver tumors. The effect of associating liver partition and portal vein ligation for staged hepatectomy on tumor proliferation, however, remains a concern. This study investigated the impact of associating liver partition and portal vein ligation for staged hepatectomy on growth of colorectal metastases in mice and in humans.

Methods: The effect of associating liver partition and portal vein ligation for staged hepatectomy and 90% portal vein ligation on colorectal liver and lung metastases was investigated in mice. In vivo tumor progression was assessed by magnetic resonance imaging, histology, and survival experiments. The effects of associating liver partition and portal vein ligation for staged hepatectomy, portal vein ligation, and control sera on cultures of several colorectal cancer cell lines (MC38 and CT26) were tested in vitro. Additionally, the international associating liver partition and portal vein ligation for staged hepatectomy registry enabled us to identify patients with remaining tumor in the future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy stage 1.

Results: Two and 3 weeks after associating liver partition and portal vein ligation for staged hepatectomy stage 1, portal vein ligation, or sham surgery, liver magnetic resonance images showed similar numbers (P=.14/0.82), sizes (P=.45/0.98), and growth kinetics (P=.58/0.68) of intrahepatic tumor. Tumor growth was not different between the associating liver partition and portal vein ligation for staged hepatectomy and portal vein ligation groups after completion of stage 2. Median survival after tumor cell injection was similar after sham surgery (36 days; 95% confidence interval; 27-57 days), completion of associating liver partition and portal vein ligation for staged hepatectomy (42 days; 95% confidence interval; 35-49 days), and portal vein ligation (39 days; 95% confidence interval; 34-43 days, P=.237). Progression of pulmonary metastases and in vitro cell proliferation were comparable among groups. Observations in humans failed to identify any accelerated tumor growth in the future liver remnant within the regenerative phase after associating liver partition and portal vein ligation for staged hepatectomy stage 1.

Conclusion: The accelerated regeneration process associated with associating liver partition and portal vein ligation for staged hepatectomy does not appear to enhance growth of colorectal metastases.
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http://dx.doi.org/10.1016/j.surg.2017.10.036DOI Listing
February 2018

Circulating complement component 4d (C4d) correlates with tumor volume, chemotherapeutic response and survival in patients with malignant pleural mesothelioma.

Sci Rep 2017 11 28;7(1):16456. Epub 2017 Nov 28.

Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Only limited information is available on the role of complement activation in malignant pleural mesothelioma (MPM). Thus, we investigated the circulating and tissue levels of the complement component 4d (C4d) in MPM. Plasma samples from 55 MPM patients, 21 healthy volunteers (HV) and 14 patients with non-malignant pleural diseases (NMPD) were measured by ELISA for C4d levels. Tissue specimens from 32 patients were analyzed by C4d immunohistochemistry. Tumor volumetry was measured in 20 patients. We found no C4d labeling on tumor cells, but on ectopic lymphoid structures within the tumor stroma. Plasma C4d levels did not significantly differ between MPM, HV or NMPD. Late-stage MPM patients had higher plasma C4d levels compared to early-stage (p = 0.079). High circulating C4d was associated with a higher tumor volume (p = 0.047). Plasma C4d levels following induction chemotherapy were significantly higher in patients with stable/progressive disease compared to those with partial/major response (p = 0.005). Strikingly, patients with low C4d levels at diagnosis had a significantly better overall survival, confirmed in a multivariate cox regression model (hazard ratio 0.263, p = 0.01). Our findings suggest that circulating plasma C4d is a promising new prognostic biomarker in patients with MPM and, moreover, helps to select patients for surgery following induction chemotherapy.
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http://dx.doi.org/10.1038/s41598-017-16551-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705645PMC
November 2017

Phase I study of a chloroquine-gemcitabine combination in patients with metastatic or unresectable pancreatic cancer.

Cancer Chemother Pharmacol 2017 Nov 4;80(5):1005-1012. Epub 2017 Oct 4.

Department of Oncology, University Hospital of Zürich, Rämistrasse 100, 8091, Zurich, Switzerland.

Purpose: Following a previously published pre-clinical validation, this phase I study evaluated the safety, maximum tolerated dose, anti-tumour activity and immune status of a gemcitabine-chloroquine combination as a first- or late-line treatment in patients with metastatic or unresectable pancreatic cancer.

Methods: In this 3 + 3 dose escalation study, patients received a single weekly standard dose of intravenous gemcitabine, followed by single weekly oral intake of 100, 200 or 300 mg of chloroquine. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Immune status was evaluated by RT-PCR to measure the relative expression of immune-related genes in peripheral blood mononuclear cells (PBMCs).

Results: Overall, nine patients [median age 72 years; interquartile range (IQR), 68-78 years] were treated. No dose-limiting toxicities as defined in the protocol were observed. Three patients experienced partial response, and two patients had stable disease. The median time to progression was 4 months (95% CI 0.8-7.2), and the median overall survival was 7.6 months (95% CI 5.3-9.9). Among 86 assayed immune genes, three were significantly differentially expressed in PBMCs from responding versus non-responding patients: interferon-gamma receptor-1, toll-like receptor 2, and beta-2 microglobulin.

Conclusions: The addition of chloroquine to gemcitabine was well tolerated and showed promising effects on the clinical response to the anti-cancer chemotherapy. Based on these initial results, the efficacy of the gemcitabine-chloroquine combination should be further assessed.
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http://dx.doi.org/10.1007/s00280-017-3446-yDOI Listing
November 2017

Impact of stroke volume assessment by integrating multi-detector computed tomography and Doppler data on the classification of aortic stenosis.

Int J Cardiol 2017 Nov;246:80-86

Cardiology, University Heart Center, University Hospital Zürich, Zürich, Switzerland. Electronic address:

Background: The prevalence of low flow low gradient (LFLG) severe aortic stenosis (AS) may be overrated due to underestimation of stroke volume in two-dimensional (2D) echocardiography. The implications of 3D imaging on stroke volume calculation for AS classification have not been elucidated. Integrating multi-detector computed tomography (MDCT) and Doppler data may improve diagnostic accuracy in patients with LFLG AS.

Methods: A total of 186 patients with severe AS evaluated for transcatheter aortic valve replacement were classified according to indexed stroke volume (SVI, cut-off 35mL/m) and mean transaortic pressure gradient (cut-off 40mmHg). SVI was calculated using a) the biplane Simpson's method, b) left ventricular outflow tract (LVOT) velocity time integral (VTI) and LVOT diameter determined by 2D echocardiography, or c) LVOT VTI and LVOT area planimetered by MDCT.

Results: SVI assessed by the biplane Simpson's method was smaller than that obtained from 2D echocardiography LVOT diameter (29.5±0.6 vs 34.9±0.8mL/m, p<0.001). The latter was smaller than SVI calculated by integrating MDCT and Doppler data (47.5±1.4mL/m, p<0.001). LFLG and paradoxical LFLG severe AS were diagnosed in 42.5% and 27.4% of patients using the biplane Simpson's method, in 30.1% and 16.7% using 2D echocardiography LVOT diameter, and in 17.2% and 8.1% when integrating MDCT and Doppler data.

Conclusions: The prevalence of LFLG and paradoxical LFLG severe AS was overestimated by 2.5- and 3.4-fold based on 2D echocardiography alone. Integration of MDCT and Doppler data should be considered for stroke volume assessment in the classification of severe AS.
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http://dx.doi.org/10.1016/j.ijcard.2017.03.112DOI Listing
November 2017

Quantification of aortic valve calcification on contrast-enhanced CT of patients prior to transcatheter aortic valve implantation.

EuroIntervention 2017 Oct;13(8):921-927

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.

Aims: The aim of the study was to develop a formula enabling the quantification of aortic valve calcification (AVC) on contrast-enhanced CT of patients undergoing transcatheter aortic valve implantation (TAVI).

Methods And Results: Two hundred and seventeen (217) consecutive patients with severe aortic valve stenosis undergoing non-enhanced electrocardiography-gated CT angiography (NECT) and contrast-enhanced electrocardiography-gated CT angiography (CECT) prior to TAVI were subdivided into a training cohort (n=145) and a validation cohort (n=72). Aortic valve calcification (AVC) was semi-automatically segmented on CECT (AVC.
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http://dx.doi.org/10.4244/EIJ-D-17-00060DOI Listing
October 2017

Value of CT signs and measurements as a predictor of pulmonary hypertension and mortality in symptomatic severe aortic valve stenosis.

Int J Cardiovasc Imaging 2017 Oct 26;33(10):1637-1651. Epub 2017 May 26.

Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.

To assess the value of computed tomography (CT) for non-invasive detection of pulmonary hypertension (PH) in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and to correlate CT measurements and signs with mortality after TAVI. 257 TAVI patients (median 84 years; 134 females) with both right heart catheterisation (RHC) and CT within 3 days were retrospectively analyzed. According to guidelines PH was defined as mean pulmonary artery pressure ≥25 mmHg in RHC. CT-signs for PH assessment were evaluated. Clinical data was recorded before and at 30 days, 1 year and 2 years after TAVI. 161 patients exhibited PH (median 83 years; 90 females). In patients with PH, main pulmonary artery diameter (MPA; p < 0.001) and anterior pericardial recess (PR; p = 0.003) were significantly larger. Furthermore, pleural effusion (p < 0.001) was significantly more common. Sensitivity and specificity for predicting PH were calculated for MPA diameter ≥29 mm (56 and 61%), PR diameter ≥10 mm (37 and 82%), and presence of pleural effusion (42 and 91%). Patients with PH showed significantly higher 2 years mortality after TAVI (30 vs. 17%; p = 0.01) with a Hazard ratio (HR) of 2.5 (95% CI 1.1-5.8; p = 0.027). Pleural effusion was a predictor of higher 2-year-all-cause mortality after TAVI (42 vs. 20%; p = 0.022) with a HR of 2.0 (95% CI 1.0-3.8; p = 0.042). Patients with symptomatic AS and PH at baseline display higher 2 year-all-cause mortality after TAVI. Several CT-signs suggest the presence of PH in TAVI patients with moderate to high specificity, but low sensitivity. Pleural effusion in CT is a predictor of higher 2 year-all-cause mortality.
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http://dx.doi.org/10.1007/s10554-017-1180-5DOI Listing
October 2017

Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy.

Br J Cancer 2017 Apr 21;116(9):1141-1147. Epub 2017 Mar 21.

Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.

Background: Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma. We developed and validated a clinical prediction scale for response to anti- PD-1 monotherapy.

Methods: A total of 315 patients with advanced melanoma treated with pembrolizumab (2 or 10 mg kg Q2W or Q3W) or nivolumab (3 mg kg Q2W) at four cancer centres between 2011 to 2013 served as the setting for the present cohort study. Variables with significant association to response on a univariate analysis were entered into a forward stepwise logistic regression model and were given a score based on ORs to calculate a clinical prediction scale.

Results: The developed clinical prediction scale included elevated LDH (1 point), age <65 years (1 point), female sex (1 point), history of ipilimumab treatment (2 points) and the presence of liver metastasis (2 points). The scale had an area under the receiver-operating curve (AUC) of 0.73 (95% CI 0.67, 0.80) in predicting response to therapy. The predictive performance of the score was maintained in the validation cohort (AUC 0.70 (95% CI 0.58, 0.81)) and the goodness-to-fit model demonstrated good calibration.

Conclusions: Based on a large cohort of patients, we developed and validated a simple five-factor prediction scale for the clinical activity of PD-1 antibodies in advanced melanoma patients. This scale can be used to stratify patients participating in clinical trials.
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http://dx.doi.org/10.1038/bjc.2017.70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418446PMC
April 2017

How much liver needs to be transected in ALPPS? A translational study investigating the concept of less invasiveness.

Surgery 2017 02 1;161(2):453-464. Epub 2016 Nov 1.

Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. Electronic address:

Background: ALPPS induces rapid liver hypertrophy after stage-1 operation, enabling safe, extended resections (stage-2) after a short period. Recent studies have suggested that partial transection at stage-1 might be associated with a better safety profile. The aim of this study was to assess the amount of liver parenchyma that needs to be divided to achieve sufficient liver hypertrophy in ALPPS.

Methods: In a bi-institutional, prospective cohort study, nonfibrotic patients who underwent ALPPS with complete (n = 22) or partial (n = 23) transection for colorectal liver metastases were analyzed and compared with an external ALPPS cohort (n = 23). A radiologic tool was developed to quantify the amount of parenchymal transection. Liver hypertrophy and clinical outcome were compared between both techniques. The relationship of partial transection and hypertrophy was investigated further in an experimental murine model of partial ALPPS.

Result: The median amount of parenchymal transection in partial ALPPS was 61% (range, 34-86%). The radiologic method correlated poorly with the intraoperative surgeon's estimation (r = 0.258). Liver hypertrophy was equivalent for the partial ALPPS, ALPPS, and external ALPPS cohort (64% vs 60% vs. 64%). Experimental data demonstrated that partial transection of at least 50% induced comparable hypertrophy (137% vs 156%) and hepatocyte proliferation compared to complete transection.

Conclusion: The study provides clinical and experimental evidence that partial liver partition of at least 50% seems to be equally effective in triggering volume hypertrophy as observed with complete transection and can be re recommended as less invasive alternative to ALPPS.
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http://dx.doi.org/10.1016/j.surg.2016.08.004DOI Listing
February 2017

Computed tomography-based three-dimensional visualisation of bone corridors and trajectories for screws in open reduction and internal fixation of symphysis diastasis: a retrospective radiological study.

Arch Orthop Trauma Surg 2016 Dec 14;136(12):1673-1681. Epub 2016 Sep 14.

Department of Surgery, Division of Trauma Surgery, University Hospital, Zurich, Switzerland.

Introduction: Typical stabilisation of pelvic open book injuries consists of plate fixation of the symphysis. No previous literature has been published about the evaluation of screw placement and their trajectory with four oblique 4.5 mm screws using a four-hole plate in symphysis diastasis. The aim of this study was to define insertion points and angles of trajectory for crossed screw placement regardless of any plate design based on an analysis of three-dimensional computed tomography data sets.

Methods: One hundred human pelvic CT data sets were collected. Unilateral and bilateral placements of crossed 4.5 mm screws were simulated. Primary outcome measure was successful simulated screw placement without cortical breach. Secondary outcome measures included the anatomical measurements of the screw positions.

Results: Simulated screw placement of two oblique screws on each side of the pubic symphysis without cortical breach was achieved in all (100 %) cases. There were a total of 400 screw simulations. Medial screws were longer, lateral screws had higher coronal angles, and the distance between both screws was higher on the right side (p < 0.001 each). The lengths of the right lateral, right medial, left lateral, and left medial screws were 44.9, 65.8, 45.4, and 67.4 mm, respectively. The sagittal angles to the dorsal surface area of the pubic rami were 10.5°, 11.1°, 9.0°, and 11.0°. The coronal angles to the vertical axis of the symphysis measured 39.5°, 16.0°, 33.8°, and 16.8°. The distances between these screws and the medial edge of the pubic crest were 33.5, 8.6, 29.5, and 7.3 mm. Furthermore, certain sex- and side-related differences were noted.

Conclusions: This series provides results about the feasibility and a detailed anatomical description of crossed screw placement. This is of special interest in pelvic surgery for choosing the entry points, safe screw channel parameters, and trajectories.
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http://dx.doi.org/10.1007/s00402-016-2568-8DOI Listing
December 2016

Prognostic value of aortic regurgitation after TAVI in patients with chronic kidney disease.

Int J Cardiol 2016 Oct 25;221:180-7. Epub 2016 Jun 25.

Department of Cardiology, University Heart Center, Zurich, Switzerland. Electronic address:

Background: Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) for severe aortic valve stenosis results in major haemodynamic changes. Influence of post-implant AR and aortic valve calcification on outcome in patients with chronic kidney disease (CKD) is unclear.

Methods: Short-term outcome was defined as a combined 30-day endpoint, long-term outcome as survival. Post-implant AR was classified as none/mild or moderate/severe using transthoracic echocardiography. Aortic valve calcification was calculated by computed tomography. Logistic regression analyses were performed in patients with none/mild (estimated glomerular filtration rate [eGFR]≥30ml/min/1.73m(2)) and advanced (eGFR<30ml/min/1.73m(2)) CKD to evaluate predictors of outcome and post-implant AR.

Results: TAVI was performed in 546 consecutive patients. Moderate/severe post-implant AR was the only independent predictor of the 30-day endpoint in patients with advanced (OR 7.091, 95% CI 1.144-43.962, p=0.035), but not in patients with none/mild CKD. Similarly, moderate/severe AR predicted impaired survival only in patients with advanced CKD (p<0.001). NT-proBNP (OR 1.023 per 500ng/l increase, 95% CI 1.003-1.043; p=0.026) before intervention was the only independent predictor of the 30-day endpoint in patients with none/mild CKD. Aortic valve calcification was comparable in patients with none/mild versus advanced CKD and was an independent predictor of moderate/severe post-implant AR in the overall population as well as in the subgroups with none/mild or advanced CKD.

Conclusions: Moderate/severe AR after TAVI predicts outcome in patients with advanced CKD, but not in patients with none/mild CKD. Aortic valve calcification is an important predictor of post-implant AR independent of kidney function.
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http://dx.doi.org/10.1016/j.ijcard.2016.06.145DOI Listing
October 2016

Circulating activin A is a novel prognostic biomarker in malignant pleural mesothelioma - A multi-institutional study.

Eur J Cancer 2016 08 8;63:64-73. Epub 2016 Jun 8.

Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Vienna, Austria; MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address:

Introduction: The deregulation of activin expression is often observed in various malignancies. Previous studies indicate that activin A plays a protumourigenic role in malignant pleural mesothelioma (MPM). The aim of the study was to evaluate circulating activin A level as a biomarker in MPM.

Methods: Plasma samples were collected from 129 MPM patients in four institutions at the time of diagnosis or before surgical resection. Samples from 45 healthy individuals and from 16 patients with non-malignant pleural diseases served as controls. Circulating activin A was measured by enzyme-linked immunosorbent assay and correlated to clinicopathological variables.

Results: Plasma activin A level was significantly elevated in MPM patients (862 ± 83 pg/ml) when compared to healthy controls (391 ± 21 pg/ml; P < 0.0001). Patients with pleuritis or fibrosis only showed a modest increase (versus controls; 625 ± 95 pg/ml; P = 0.0067). Sarcomatoid (n = 10, 1629 ± 202 pg/ml, P = 0.0019) and biphasic (n = 23, 1164 ± 233 pg/ml, P = 0.0188) morphology were associated with high activin A levels when compared to epithelioid histology (n = 94, 712 ± 75 pg/ml). The tumour volume showed a positive correlation with increased circulating activin A levels. MPM patients with below median activin A levels had a significantly longer overall survival when compared to those with high activin A levels (median survival 735 versus 365 d, P < 0.0001). Importantly, circulating activin A levels were exclusively prognostic in epithelioid MPM.

Conclusions: Our findings suggest that the measurement of circulating activin A may support the histological classification of MPM and at the same time help to identify epithelioid MPM patients with poor prognosis.
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http://dx.doi.org/10.1016/j.ejca.2016.04.018DOI Listing
August 2016

Treatment of isolated ascending aortic aneurysm by off-pump epiaortic wrapping is safe and durable.

Interact Cardiovasc Thorac Surg 2016 08 15;23(2):286-91. Epub 2016 Apr 15.

Clinic for Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland.

Objectives: Isolated ascending aortic aneurysm (iAA) is usually treated by open graft repair requiring sternotomy, cardiopulmonary bypass (CPB) and cardioplegia. This approach carries significant mortality in older patients or those presenting with comorbidities. We report an original series of patients presenting with iAA and treated with epiaortic wrapping by using a synthetic mesh. This less invasive aortic repair technique allows reducing the aortic diameter to a predefined value and is performed without CPB.

Methods: Data from patients presenting with an iAA and treated with the wrapping technique (WT) by polypropylene/polyester mesh from November 2006 to July 2015 were collected. The end-points that were analysed included maximal aortic transverse diameter, perioperative mortality and morbidity, survival, freedom from reinterventions and aortic valve function during follow-up. The maximal aneurysm transverse diameter was analysed based on contrast-enhanced computed tomography (CTA) or magnetic resonance (MR) performed preoperatively, and during the follow-up.

Results: The off-pump WT was used in 33 cases with no perioperative mortality. The median radiological follow-up was 33.47 (range: 1-106) months. Overall, the WT achieved a 30% diameter reduction. The mean preoperative and postoperative ascending aortic transverse diameter was 5.5 cm [standard deviation (SD): 0.6] and 3.7 cm (SD: 0.30), respectively (P = 0.001). In addition, CTA or MR follow-up showed stable diameters at the level of the aortic root and the distal ascending aorta. No death occurred during the follow-up. At 5 years, the estimated freedom rate from reinterventions of the aortic root and ascending aorta was 94%.

Conclusions: This series shows that the WT with a polypropylene/polyester mesh allows safe off-pump treatment of patients with iAA. Mid- and long-term results are promising. This technique could be an attractive alternative, especially for patients unfit for aortic surgery with CPB and cardioplegia.
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http://dx.doi.org/10.1093/icvts/ivw103DOI Listing
August 2016

Calcification Characteristics of Low-Flow Low-Gradient Severe Aortic Stenosis in Patients Undergoing Transcatheter Aortic Valve Replacement.

Cardiol Res Pract 2015 7;2015:802840. Epub 2015 Sep 7.

University Heart Center, Department of Cardiology, University Hospital Zürich, 8091 Zürich, Switzerland.

Low-flow low-gradient severe aortic stenosis (LFLGAS) is associated with worse outcomes. Aortic valve calcification patterns of LFLGAS as compared to non-LFLGAS have not yet been thoroughly assessed. 137 patients undergoing transcatheter aortic valve replacement (TAVR) with preprocedural multidetector computed tomography (MDCT) and postprocedural transthoracic echocardiography were enrolled. Calcification characteristics were assessed by MDCT both for the total aortic valve and separately for each leaflet. 34 patients had LFLGAS and 103 non-LFLGAS. Total aortic valve calcification volume (p < 0.001), mass (p < 0.001), and density (p = 0.004) were lower in LFLGAS as compared to non-LFLGAS patients. At 30-day follow-up, mean transaortic pressure gradients and more than mild paravalvular regurgitation did not differ between groups. In conclusion, LFLGAS and non-LFLGAS express different calcification patterns which, however, did not impact on device success after TAVR.
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http://dx.doi.org/10.1155/2015/802840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576007PMC
October 2015

Correlation of pelvic incidence with radiographical parameters for acetabular retroversion: a retrospective radiological study.

BMC Med Imaging 2015 Sep 29;15:39. Epub 2015 Sep 29.

Department of Surgery, Division of Trauma Surgery, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.

Background: Pelvic incidence (PI) has been linked to several degenerative processes within the spinopelvic system. Acetabular retroversion is a recognised risk factor for osteoarthritis of the hip. We therefore hypothesised that these two factors might be part of a specific anatomical variant associated with degenerative changes. This study was performed to clarify this issue.

Methods: The pelvic incidence was measured on 589 computertomographical data sets acquired between 2008 and 2010. For 220 patients a 2D rendering in an antero-posterior view of the CT data set was performed to evaluate the parameters of acetabular retroversion. Those included the prominence of the ischial spine sign (PRISS), the cross-over sign (COS) and the posterior wall sign (PWS). Between 477 and 478 hips were evaluated depending on the parameter of retroversion.

Results: The mean pelvic incidence was significantly lower in hips positive for the PRISS and the PWS. However, there were no significant differences between hips positive or negative for the COS.

Discussion: As hypothesised, the lower PI values in PWS and PRISS positive hips suggest a link between PI and retroversion of the acetabulum. Whether this is of any clinical relevance remains, however, unknown.

Conclusion: Acetabular retroversion is linked to PI. In hips where the prominence of the ischial spine sign and/or the posterior wall sign was present, the mean pelvic incidence value was lower.
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http://dx.doi.org/10.1186/s12880-015-0080-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589032PMC
September 2015

A New Prognostic Score Supporting Treatment Allocation for Multimodality Therapy for Malignant Pleural Mesothelioma: A Review of 12 Years' Experience.

J Thorac Oncol 2015 Nov;10(11):1634-41

*Division of Thoracic Surgery, †Department of Diagnostic Radiology, University Hospital Zurich, Zurich, Switzerland; ‡Department of Biostatistics, Epidemiology, Biostatistics and Prevention Unit, University Zurich, Zurich, Switzerland; §Division of Thoracic Surgery, Medical University Vienna, Vienna, Austria; and ‖Laboratory of Molecular Oncology, University Hospital Zurich, Zurich, Switzerland.

Introduction: Treatment of malignant pleural mesothelioma (MPM) remains a clinical challenge. The aim of this study was to identify selection factors for allocation of MPM patients to multimodal therapy based on survival data from 12 years of experience.

Methods: Eligible patients had MPM of all histological subtypes with clinical stage T1-3 N0-2 M0. Induction chemotherapy consisted of cisplatin/gemcitabine (cis/gem) or cisplatin/pemetrexed (cis/pem), followed by extrapleural pneumonectomy (EPP). Multivariate analysis was performed to assess independent prognosticators for overall survival (OS). A Multimodality Prognostic Score was developed based on clinical variables available before surgery.

Results: From May 1999 to August 2011, 186 MPM patients were intended to be treated with induction chemotherapy followed by EPP. Hematologic toxicity was significantly less frequent after cis/pem compared to cis/gem, but there was no difference in response or OS between the regimens. One hundred and twenty-eight patients underwent EPP with a 30-day mortality of 4.7%. Fifty-two percent of the patients received adjuvant radiotherapy. The median OS of patients undergoing EPP was significantly longer with 22 months (95% confidence interval: 20-24) when compared to 11 months (9-12) for patients treated without EPP. A prognostic score was defined considering tumor volume, histology, C-reactive protein level, and response to chemotherapy that identified patient groups not benefitting from multimodality treatment which was confirmed in an independent cohort.

Conclusion: Patients receiving induction chemotherapy followed by EPP for MPM of all histological subtypes and irrespective of nodal status showed a median survival of 22 months. A prognostic score is proposed to help patient allocation for surgery after validation in an independent cohort.
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http://dx.doi.org/10.1097/JTO.0000000000000661DOI Listing
November 2015

Interpretation of bedside chest X-rays in the ICU: is the radiologist still needed?

Clin Imaging 2015 Nov-Dec;39(6):1018-23. Epub 2015 Jul 23.

University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Rämistrasse 100, CH-8091 Zürich. Electronic address:

Purpose: To compare diagnostic accuracy of intensivists to radiologists in reading bedside chest X-rays.

Methods: In a retrospective trial, 33 bedside chest X-rays were evaluated by five radiologists and five intensivists with different experience. Images were evaluated for devices and lung pathologies. Interobserver agreement and diagnostic accuracy were calculated. Computed tomography served as reference standard.

Results: Seniors had higher diagnostic accuracy than residents (mean-ExpB(Senior)=1.456; mean-ExpB(Resident)=1.635). Interobserver agreement for installations was more homogenously distributed between radiologists compared to intensivists (ExpB(Rad)=1.204-1.672; ExpB(Int)=1.005-2.368). Seniors had comparable diagnostic accuracy.

Conclusion: No significant difference in diagnostic performance was seen between seniors of both disciplines, whereas the resident intensivists might still benefit from an interdisciplinary dialogue.
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http://dx.doi.org/10.1016/j.clinimag.2015.07.024DOI Listing
June 2016

Prosthesis-Specific Predictors of Paravalvular Regurgitation after Transcatheter Aortic Valve Replacement: Impact of Calcification and Sizing on Balloon-Expandable versus Self-Expandable Transcatheter Heart Valves.

J Heart Valve Dis 2015 Jan;24(1):10-21

Background And Aim Of The Study: The study aim was to investigate prosthesis-specific predictors for paravalvular aortic regurgitation (PAR) in self-expandable versus balloon-expandable transcatheter heart valves (THVs). PAR is frequently observed after transcatheter aortic valve replacement (TAVR). As self-expandable and balloon-expandable THVs engage differently with the native aortic valve structures, factors that impact PAR may differ between the prosthesis types.

Methods: A total of 137 TAVR patients who underwent pre-procedural multidetector computed tomography and post-procedural transthoracic echocardiography were studied. Predictors for PAR, including annulus area oversizing and aortic valve calcification mass and volume, were analyzed in a multivariate model.

Results: The Medtronic CoreValve (MCV) prosthesis was utilized in 68 patients (50%), and the Edwards SAPIEN (ES) prosthesis in 69 (50%). More than mild PAR was observed in 43 patients (32%). Among MCV patients, aortic valve calcification volume and mass were higher in those with more than mild PAR than in those with none or mild PAR (p = 0.04, p = 0.03, respectively). Among ES patients, the annulus area and perimeter oversizing were lower in those with more than mild PAR compared to those with no or mild PAR (p = 0.001). By univariate and multivariate logistic regression analysis, aortic valve calcification mass was the only independent predictor for PAR in MCV patients (p = 0.02), whereas in ES patients it was THV undersizing (p = 0.002), irrespective of the calcific burden.

Conclusion: For self-expandable THVs, aortic valve calcification mass was the strongest predictor of PAR, whereas for balloon-expandable THVs it was prosthesis undersizing. Hence, in patients evaluated for TAVR these parameters should guide the selection of prosthesis type.
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January 2015