Multicentre retrospective analysis on pulmonary metastasectomy: an European perspective.

OBJECTIVES: To assess the current practice of pulmonary metastasectomy at 15 European Centres. Short- and long-term outcomes were analysed. METHODS: Retrospective analysis on patients ≥18 years who underwent curative-intent pulmonary metastasectomy (January 2010 to December 2018). Data were collected on a purpose-built database (REDCap). Exclusion criteria were: previous lung/extrapulmonary metastasectomy, pneumonectomy, non-curative intent and evidence of extrapulmonary recurrence at the time of lung surgery. RESULTS: A total of 1647 patients [mean age 59.5 (standard deviation; SD = 13.1) years; 56.8% males] were included. The most common primary tumour was colorectal adenocarcinoma. The mean disease-free interval was 3.4 (SD = 3.9) years. Relevant comorbidities were observed in 53.8% patients, with a higher prevalence of metabolic disorders (32.3%). Video-assisted thoracic surgery was the chosen approach in 54.9% cases. Wedge resections were the most common operation (67.1%). Lymph node dissection was carried out in 41.4% cases. The median number of resected lesions was 1 (interquartile range 25-75% = 1-2), ranging from 1 to 57. The mean size of the metastases was 18.2 (SD = 14.1) mm, with a mean negative resection margin of 8.9 (SD = 9.4) mm. A R0 resection of all lung metastases was achieved in 95.7% cases. Thirty-day postoperative morbidity was 14.5%, with the most frequent complication being respiratory failure (5.6%). Thirty-day mortality was 0.4%. Five-year overall survival and recurrence-free survival were 62.0% and 29.6%, respectively. CONCLUSIONS: Pulmonary metastasectomy is a low-risk procedure that provides satisfactory oncological outcomes and patient survival. Further research should aim at clarifying the many controversial aspects of its daily clinical practice.

Approach for tuberculosis-associated immune reconstitution inflammatory syndrome in an HIV-negative patient.

A male refugee from the Middle East was diagnosed with pulmonary tuberculosis and Pott's disease with paravertebral abscess. After starting the standard regimen, the sputum culture converted to negative and the patient's general condition improved. Six weeks later, the patient presented with clinical worsening of known symptoms, new appearance of focal neurological deficits and progress of radiological features showing progression of the paravertebral abscess. Immune reconstitution inflammatory syndrome with Mycobacterium tuberculosis (TB-IRIS) was presumed, and treatment with high-dose steroids was started. Due to recurrent relapses while tapering, corticosteroids had to be given over a prolonged period. After treatment completion, the patient was in a good general condition, abscesses had decreased and neurological deficits were in complete remission. This case presents the rare manifestation of TB-IRIS in HIV-negative patients and its management in a high-income country.

Diffusion Tensor Imaging of the Brachial Plexus: A Comparison between Readout-segmented and Conventional Single-shot Echo-planar Imaging.

PURPOSE: Diffusion tensor imaging (DTI) adds functional information to morphological magnetic resonance neurography (MRN) in the assessment of the brachial nerve plexus. To determine the most appropriate pulse sequence in scan times suited for diagnostic imaging in clinical routine, we compared image quality between simultaneous multi-slice readout-segmented (rs-DTI) and conventional single-shot (ss-DTI) echo-planar imaging techniques. METHODS: Institutional Review Board (IRB) approved study including 10 healthy volunteers. The supraclavicular brachial plexus, covering the nerve roots and trunks from C5 to C7, was imaged on both sides with rs-DTI and ss-DTI. Both sequences were acquired in scan times <7 min with b-values of 900 s/mm2 and with isotropic spatial resolution. RESULTS: In rs-DTI image, the overall quality was significantly better and distortion artifacts were significantly lower (P = 0.001-0.002 and P = 0.001-0.002, respectively) for both readers. In ss-DTI, a trend toward lower degree of ghosting and motion artifacts was elicited (reader 1, P = 0.121; reader 2, P = 0.264). No significant differences between the two DTI techniques were found for signal-to-noise ratios (SNR), contrast-to-noise ratios (CNR) and fractional anisotropy (FA) (P ≥ 0.475, P ≥ 0.624, and P ≥ 0.169, respectively). Interreader agreement for all examined parameters and all sequences ranged from intraclass correlation coefficient (ICC) 0.064 to 0.905 and Kappa 0.40 to 0.851. CONCLUSION: Incomparable acquisition times rs-DTI showed higher image quality and less distortion artifacts than ss-DTI. The trend toward a higher degree of ghosting and motion artifacts in rs-DTI did not deteriorate image quality to a significant degree. Thus, rs-DTI should be considered for functional MRN of the brachial plexus.

Lesion magnetic susceptibility response to hyperoxic challenge: A biomarker for malignant brain tumor microenvironment?

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been previously used to differentiate lesions in patients with brain tumors. The aim of this work was to characterize the response of magnetic susceptibility differences in malignant brain tumors and surrounding edema to hyperoxic and hypercapnic respiratory challenges. METHODS: Images of malignant brain tumor patients (2 glioblastoma multiforme, 2 anaplastic astrocytoma, 1 brain metastasis) with clinical MRI exams (contrast-enhanced T1w) were acquired at 3T. 3D multi-gradient-echo data sets were acquired while the patients inhaled medical-air (21% O2), oxygen (100% O2), and carbogen (95% O2, 5% CO2). Susceptibility maps were generated from real and imaginary data. Regions of interest were analyzed with respect to respiration-gas-induced susceptibility changes. RESULTS: Contrast-enhancing tumor regions with high baseline magnetic susceptibility exhibited a marked susceptibility reduction under hyperoxic challenges, with a stronger effect (-0.040 to -0.100ppm) under hypercapnia compared to hyperoxia (-0.010 to -0.067ppm). In contrast, regions attributed to necrotic tissue and to edema showed smaller changes of opposite sign, i.e. paramagnetic shift. There was a correlation between malignant tumor tissue magnetic susceptibility at baseline under normoxia and the corresponding susceptibility reduction under hypercapnia and - to a lesser degree - under hyperoxia. CONCLUSION: In this small cohort of analysis, quantification of susceptibility changes in response to respiratory challenges allowed a complementary, functional differentiation of tumorous sub-regions. Those changes, together with the correlations observed between baseline susceptibility under normoxia and susceptibility reduction with challenges, could prove helpful for a non-invasive characterization of local tumor microenvironment.

Evaluation of Reproducibility of Diffusion Tensor Imaging in the Brachial Plexus at 3.0 T.

OBJECTIVE: The aim of this study was to evaluate the reproducibility of 3 T magnetic resonance imaging diffusion tensor imaging (DTI) of the brachial plexus in healthy subjects. METHODS: Ten healthy volunteers were included, and morphological and DTI sequences of the nerve roots of the brachial plexus from C5 to T1 of both sides were repeatedly acquired on a 3 T magnetic resonance system (MAGNETOM Skyra; Siemens Healthcare, Erlangen, Germany). A prototype diffusion-weighted single-shot echo-planar imaging sequence-enabling slice-specific shim adjustments was performed with b-values of 0 and 800 s/mm in 30 gradient directions, resulting in an acquisition time of about 6 minutes each in axial orientation. Between scans, subjects were moved and repositioned in the scanner, coils were reinserted, and new localizers were acquired. Image analysis was performed using MITK Diffusion software toolkit. Two independent readers performed diffusion data postprocessing, and regions of interest (ROIs) were set on the proximal postganglionic trunk at each spinal level, bilaterally to obtain values for fractional anisotropy (FA) and mean diffusivity (MD). Interreader and intrareader agreement as well as test-retest reproducibility of DTI metrics were assessed. RESULTS: Intraclass correlation coefficients (ICCs) for interreader and intrareader agreement did not differ significantly between measurements for FA and MD. In particular, ICCs for interreader agreement of FA ranged from 0.741 to 0.961 and that of MD ranged from 0.802 to 0.998, and ICCs for intrareader agreement of FA ranged from 0.759 to 0.949 and that of MD ranged from 0.796 to 0.998. The test-retest reproducibility of DTI metrics showed an overall moderate to strong correlation (r > 0.707), with few minor exceptions, for both FA and MD values. CONCLUSIONS: Diffusion tensor imaging metrics in the brachial plexus are reproducible. Future applications of DTI for a possible clinical use should be further investigated.

Diffusion Tensor Imaging of Lumbar Nerve Roots: Comparison Between Fast Readout-Segmented and Selective-Excitation Acquisitions.

OBJECTIVES: The aim of this study was to compare the quality of recently emerged advanced diffusion tensor imaging (DTI) techniques with conventional single-shot echo-planar imaging (EPI) in a functional assessment of lumbar nerve roots. MATERIALS AND METHODS: The institutional review board approved the study including 12 healthy volunteers. Diffusion tensor imaging was performed at 3 T (MAGNETOM Skyra; Siemens Healthcare) with b-values of 0 and 700 s/mm and an isotropic spatial resolution for subsequent multiplanar reformatting. The nerve roots L2 to S1 were imaged in coronal orientation with readout-segmented EPI (rs-DTI) and selective-excitation EPI (sTX-DTI) with an acquisition time of 5 minutes each, and in axial orientation with single-shot EPI (ss-DTI) with an acquisition time of 12 minutes (scan parameters as in recent literature). Two independent readers qualitatively and quantitatively assessed image quality. RESULTS: The interobserver reliability ranged from "substantial" to "almost perfect" for all examined parameter and all 3 sequences (κ = 0.70-0.94). Overall image quality was rated higher, and artifact levels were scored lower for rs-DTI and sTX-DTI than for ss-DTI (P = 0.007-0.027), while fractional anisotropy and signal-to-noise ratio values were similar for all sequences (P ≥ 0.306 and P ≥ 0.100, respectively). Contrast-to-noise ratios were significantly higher for rs-DTI and ss-DTI than for sTX-DTI (P = 0.004-0.013). CONCLUSIONS: Despite shorter acquisition times, rs-DTI and sTX-DTI produced images of higher quality with smaller geometrical distortions than the current standard of reference, ss-DTI. Thus, DTI acquisitions in the coronal plane, requiring fewer slices for full coverage of exiting nerve roots, may allow for functional neurography in scan times suitable for routine clinical practice.

A single-dose mass balance and metabolite-profiling study of vemurafenib in patients with metastatic melanoma.

Vemurafenib, a selective inhibitor of oncogenic BRAF kinase carrying the V600 mutation, is approved for treatment of advanced BRAF mutation-positive melanoma. This study characterized mass balance, metabolism, rates/routes of elimination, and disposition of (14)C-labeled vemurafenib in patients with metastatic melanoma. Seven patients with metastatic BRAF-mutated melanoma received unlabeled vemurafenib 960 mg twice daily for 14 days. On the morning of day 15, patients received (14)C-labeled vemurafenib 960 mg (maximum 2.56 MBq [69.2 µCi]). Thereafter, patients resumed unlabeled vemurafenib (960 mg twice daily). Blood, urine, and feces were collected for metabolism, pharmacokinetic, and dose recovery analysis. Within 18 days after dose, ∽95% of (14)C-vemurafenib-related material was recovered from feces (94.1%) and urine (<1%). The parent compound was the predominant component (95%) in plasma. The mean plasma elimination half-life of (14)C-vemurafenib-related material was 71.1 h. Each metabolite accounted for <0.5% and ≤6% of the total administered dose in urine and feces, respectively (0-96 h postdose). No new metabolites were detected. Vemurafenib was well-tolerated. Excretion of vemurafenib via bile into feces is considered the predominant elimination route from plasma with minor renal elimination (<1%). e00113.

Clinical positron emission tomography/magnetic resonance imaging applications.

Although clinical positron emission tomography (PET)/computed tomography (CT) applications were obvious and have completely replaced PET in oncology, clinical applications of PET/magnetic resonance (MR) are currently not clearly defined. This is due to the lack of clinical data, which is mainly because PET/MR technology is not clinically mature at this point. Open issues are technical and concern ease of obtaining PET attenuation correction maps, dealing with, for example, MR surface coil metal in the PET field-of-view and appropriate workflows leading to a cost-effective examination. All issues can be circumvented by using a shuttle-connected PET/CT-MR system, but the penalty is that simultaneous PET and MR imaging are not possible and potential motion between examinations may occur. Clinically, some systems installed worldwide start to have a reasonable bulk of clinical data. Preliminary results suggest that in oncology, PET/MR may have advantages over PET/CT in head and neck imaging. In liver imaging, more PET-positive lesions are seen on MR than on CT, but that does not mean that PET/MR is superior to PET/CT. Possibly in some settings where a contrast-enhanced PET/CT is needed to be diagnostic, PET/MR can be done without contrast media. Although PET/CT has virtually no role in brain imaging, this may be an important domain for PET/MR, particularly in dementia imaging. The role of PET/MR in the heart is as yet undefined, and much research will have to be done to elucidate this role. At this point, it is also not clear where the simultaneity afforded by a fully integrated PET/MR is really needed. Sequential data acquisition even on separate systems and consecutive software image fusion may well be appropriate. With the increasing installed base of systems, clinical data will be forthcoming and define more clearly where there is clinical value in PET/MR at an affordable price.

PET-MR imaging using a tri-modality PET/CT-MR system with a dedicated shuttle in clinical routine.

Tri-modality PET/CT-MRI includes the transfer of the patient on a dedicated shuttle from one system into the other. Advantages of this system include a true CT-based attenuation correction, reliable PET-quantification and higher flexibility in patient throughput on both systems. Comparative studies of PET/MRI versus PET/CT are readily accomplished without repeated PET with a different PET scanner at a different time point. Additionally, there is a higher imaging flexibility based on the availability of three imaging modalities, which can be combined for the characterization of the disease. The downside is a somewhat higher radiation dose of up to 3 mSv with a low dose CT based on the CT-component, longer acquisition times and potential misalignment between the imaging components. Overall, the tri-modality PET/CT-MR system offers comparative studies using the three different imaging modalities in the same patient virtually at the same time, and may help to develop reliable attenuation algorithms at the same time.