Objective: Endovascular thrombectomy (EVT) is the standard of care for acute large vessel occlusion stroke. Recently, the ANGEL-ASPECT and SELECT 2 trials showed improved outcomes in patients with acute ischemic Stroke presenting with large infarcts. The cost-effectiveness of EVT for this subpopulation of stroke patients has only been calculated using data from the previously published RESCUE-Japan LIMIT trial. It is, therefore, limited in its generalizability to an international population. With this study we primarily simulated patient-level costs to analyze the economic potential of EVT for patients with large ischemic stroke from a public health payer perspective based on the recently published data and secondarily identified determinants of cost-effectiveness. Methods: Costs and outcome of patients treated with EVT or only with the best medical care based on the recent prospective clinical trials ANGEL-ASPECT, SELECT2 and RESCUE-Japan LIMIT. A A Markov model was developed using treamtment outcomes derived from the most recent available literature. Deterministic and probabilistic sensitivity analyses addressed uncertainty. Results: Endovascular treatment resulted in an incremental gain of 1.32 QALYs per procedure with cost savings of $17,318 per patient. Lifetime costs resulted to be most sensitive to the costs of the endovascular procedure. Conclusion: EVT is a cost-saving (i.e., dominant) strategy for patients presenting with large ischemic cores defined by inclusion criteria of the recently published ANGEL-ASPECT, SELECT2, and RESCUE-Japan LIMIT trials in comparison to best medical care in our simulation. Prospective data of individual patients need to be collected to validate these results.
This study evaluated a deep neural network (DNN) algorithm for automated aortic diameter quantification and aortic dissection detection in chest computed tomography (CT). A total of 100 patients (median age: 67.0 [interquartile range 55.3/73.0] years; 60.0% male) with aortic aneurysm who underwent non-enhanced and contrast-enhanced electrocardiogram-gated chest CT were evaluated. All the DNN measurements were compared to manual assessment, overall and between the following subgroups: (1) ascending (AA) vs. descending aorta (DA); (2) non-obese vs. obese; (3) without vs. with aortic repair; (4) without vs. with aortic dissection. Furthermore, the presence of aortic dissection was determined (yes/no decision). The automated and manual diameters differed significantly (p < 0.05) but showed excellent correlation and agreement (r = 0.89; ICC = 0.94). The automated and manual values were similar in the AA group but significantly different in the DA group (p < 0.05), similar in obese but significantly different in non-obese patients (p < 0.05) and similar in patients without aortic repair or dissection but significantly different in cases with such pathological conditions (p < 0.05). However, in all the subgroups, the automated diameters showed strong correlation and agreement with the manual values (r > 0.84; ICC > 0.9). The accuracy, sensitivity and specificity of DNN-based aortic dissection detection were 92.1%, 88.1% and 95.7%, respectively. This DNN-based algorithm enabled accurate quantification of the largest aortic diameter and detection of aortic dissection in a heterogenous patient population with various aortic pathologies. This has the potential to enhance radiologists' efficiency in clinical practice.
BACKGROUND: Molecular changes in HCC development are largely unknown. As the liver plays a fundamental role in the body's metabolism, metabolic changes are to be expected. AIMS: We aimed to identify metabolomic changes in HCC in comparison to liver cirrhosis (LC) patients, which could potentially serve as novel biomarkers for HCC diagnosis and prognosis. METHODS: Metabolite expression from 38 HCC from the SORAMIC trial and 32 LC patients were analyzed by mass spectrometry. Metabolites with significant differences between LC and HCC at baseline were analyzed regarding expression over follow-up. In addition, association with overall survival was tested using univariate Cox proportional-hazard analysis. RESULTS: 41 metabolites showed differential expression between LC and HCC patients. 14 metabolites demonstrated significant changes in HCC patients during follow-up. Campesterol, lysophosphatidylcholine, octadecenoic and octadecadienoic acid, and furoylglycine showed a differential expression in the local ablation vs. palliative care group. High expression of eight metabolites (octadecenoic acid, 2-hydroxybutyrate, myo-inositol, isocitrate, erythronic acid, creatinine, pseudouridine, and erythrol) were associated with poor overall survival. The association between poor OS and octadecenoic acid and creatinine remained statistically significant even after adjusting for tumor burden and LC severity. CONCLUSION: Our findings give promising insides into the metabolic changes during HCC carcinogenesis and provide candidate biomarkers for future studies. Campesterol and furoylglycine in particular were identified as possible biomarkers for HCC progression. Moreover, eight metabolites were detected as predictors for poor overall survival.
Introduction Early diagnosis of hepatocellular carcinoma as well as evaluation of prognosis and prediction of treatment efficacy remain challenging due to the missing specific non-invasive biomarkers. The aim of this study is to identify disease-specific microRNA (miRNA) patterns for diagnosis, prediction of prognosis and treatment response in patients with hepatocellular carcinoma (HCC). Methods The study population included 42 HCC patients from SORAMIC clinical trial: 22 patients received sorafenib monotherapy, 20 patients underwent 90Y radioembolization in combination with sorafenib. 20 individuals were included in the control group. Hepatocellular carcinoma patients underwent collection of plasma samples before and 7-9 weeks after the beginning of the treatment. Isolation of circulating miRNAs, preparation of small RNA sequencing libraries and next-generation sequencing were performed. Association analysis for novel diagnostic, prognostic and treatment-related candidate biomarkers was performed. Results A total of 42 differentially expressed (16 up-regulated and 26 down-regulated) miRNAs were identified comparing baseline and control group plasma samples. hsa-miR-215-5p and hsa-miR-192-5p were down-regulated, while hsa-miR-483-5p and hsa-miR-23b-3p were up-regulated comparing baseline and 7-9 weeks post-sorafenib monotherapy samples. hsa-miR-215-5p was the sole down-regulated miRNA in the same combination therapy comparison. hsa-miR-183-5p, hsa-miR-28-3p and hsa-miR-1246 were found to be significantly up-regulated comparing non-responders versus responders to sorafenib. High hsa-miR-215-5p expression was significantly associated with worse HCC patients' prognosis. Conclusions Systematic miRNA profiling of highly characterized samples from SORAMIC study revealed a subset of potential miRNA biomarkers for hepatocellular carcinoma diagnosis and prognosis of sorafenib-treated patients' survival.
OBJECTIVES: To evaluate the safety and clinical outcome of bleomycin electrosclerotherapy (BEST) for treating extracranial slow-flow malformations. METHODS: In this retrospective investigation of a multicenter cohort presenting symptomatic slow-flow malformations, patient records were analyzed with respect to procedural details and complications. A treatment-specific, patient-reported questionnaire was additionally evaluated, obtained 3-12 months after the last treatment, to assess the subjective outcomes, including mobility, aesthetic aspects, and pain, as well as the occurrence of postprocedural skin hyperpigmentation. All outcome parameters were compared according to patients' age. RESULTS: Overall, 325 BEST treatments were performed in 233 patients after intralesional and/or intravenous bleomycin injection. The total complication rate was 10.2% (33/325), including 29/352 (8.9%) major complications. Patient-reported mobility decreased in 10/133 (8.8%), was stable in 30/113 (26.5%), improved in 48/113 (42.5%), and was rated symptom-free in 25/113 (22.1%) patients. Aesthetic aspects were rated impaired compared to baseline in 19/113 (16.8%), stable in 21/133 (18.6%), improved in 62/113 (54.9%), and perfect in 11/133 (9.7%) patients. Postprocedural skin hyperpigmentation occurred in 78/113 (69%) patients, remaining unchanged in 24/78 (30.8%), reduced in 51/78 (65.5%), and completely resolved in 3/78 (3.8%) patients. The median VAS pain scale was 4.0 (0-10) preprocedural and 2.0 (0-9) postprocedural. Children/adolescents performed significantly better in all parameters compared to adults (≥ 16 years) (mobility, p = 0.011; aesthetic aspects, p < 0.001; pain, p < 0.001). CONCLUSIONS: BEST is effective for treating slow-flow vascular malformations, with few but potentially significant major complications. Regarding patient-reported outcomes, children seem to benefit better compared to older patients, suggesting that BEST should not be restricted to adults. CLINICAL RELEVANCE STATEMENT: Bleomycin electrosclerotherapy is a safe and effective approach and therapy should not be restricted to adults due to good clinical outcomes in children.
BACKGROUND: This study explores the predictive and monitoring capabilities of clinical and multiparametric MR parameters in assessing capecitabine and temozolomide (CAPTEM) therapy response in patients with neuroendocrine tumors (NET). PATIENTS AND METHODS: This retrospective study (n = 44) assessed CAPTEM therapy response in neuroendocrine liver metastases (NELM) patients. Among 33 monitored patients, as a subgroup of the overall study cohort, pretherapeutic and follow-up MRI data (size, apparent diffusion coefficient [ADC] values, and signal intensities), along with clinical parameters (chromogranin A [CgA] and Ki-67%), were analyzed. Progression-free survival (PFS) served as the reference. Responders were defined as those with PFS ≥ 6 months. RESULTS: Most patients were male (75%) and had G2 tumors (76%) with a pancreatic origin (84%). Median PFS was 5.7 months; Overall Survival (OS) was 25 months. Non-responders (NR) had higher Ki-67 in primary tumors (16.5 vs. 10%, p = 0.01) and increased hepatic burden (20% vs. 5%, p = 0.007). NR showed elevated CgA post-treatment, while responders (R) exhibited a mild decrease. ADC changes differed significantly between groups, with NR having decreased ADCmin (-23%) and liver-adjusted ADCmean/ADCmean liver (-16%), compared to R's increases of ADCmin (50%) and ADCmean/ADCmean liver (30%). Receiver operating characteristic (ROC) analysis identified the highest area under the curve (AUC) (0.76) for a single parameter for ∆ ADC mean/liver ADCmean, with a cut-off of < 6.9 (76% sensitivity, 75% specificity). Combining ∆ Size NELM and ∆ ADCmin achieved the best balance (88% sensitivity, 60% specificity) outperforming ∆ Size NELM alone (69% sensitivity, 65% specificity). Kaplan-Meier analysis indicated significantly longer PFS for ∆ ADCmean/ADCmean liver < 6.9 (p = 0.024) and ∆ Size NELM > 0% + ∆ ADCmin < -2.9% (p = 0.021). CONCLUSIONS: Survival analysis emphasizes the need for adapted response criteria, involving combined evaluation of CgA, ADC values, and tumor size for monitoring CAPTEM response in hepatic metastasized NETs.
For decades, treatment of advanced biliary tract cancer (BTC) was confined to the use of chemotherapy. In recent years however, the number of therapeutic options available for patients with unresectable BTC have drastically increased, with immunotherapy and targeted treatment gradually joining the ranks of guideline-recommended treatment regimens. The aim of the present review is to summarise the current knowledge on unresectable BTC focusing on epidemiology, anatomical distribution and current strategies for systemic treatment. We further outline ongoing clinical trials and provide an outlook on future therapeutic interventions. In the realm of gastrointestinal malignancies, the increasing number of systemic treatment options for BTC is finally delivering on the longstanding commitment to personalised oncology. This emphasises the need for considering a comprehensive genomic-based pathology assessment right from the initial diagnosis to fully leverage the expanding array of therapeutic options that have recently become accessible.
Biliary Tract Neoplasms , Humans , Biliary Tract Neoplasms/therapy , Biliary Tract Neoplasms/drug therapy , Biliary Tract Neoplasms/pathology , Immunotherapy/methods , Molecular Targeted Therapy/methods
BACKGROUND: We aimed to correlate alterations in the rat sarcoma virus (RAS)/mitogen-activated protein kinase pathway in vascular anomalies to the clinical phenotype for improved patient and treatment stratification. METHODS AND RESULTS: This retrospective multicenter cohort study included 29 patients with extracranial vascular anomalies containing mosaic pathogenic variants (PVs) in genes of the RAS/mitogen-activated protein kinase pathway. Tissue samples were collected during invasive treatment or clinically indicated biopsies. PVs were detected by the targeted sequencing of panels of genes known to be associated with vascular anomalies, performed using DNA from affected tissue. Subgroup analyses were performed according to the affected genes with regard to phenotypic characteristics in a descriptive manner. Twenty-five vascular malformations, 3 vascular tumors, and 1 patient with both a vascular malformation and vascular tumor presented the following distribution of PVs in genes: Kirsten rat sarcoma viral oncogene (n=10), neuroblastoma ras viral oncogene homolog (n=1), Harvey rat sarcoma viral oncogene homolog (n=5), V-Raf murine sarcoma viral oncogene homolog B (n=8), and mitogen-activated protein kinase kinase 1 (n=5). Patients with RAS PVs had advanced disease stages according to the Schobinger classification (stage 3-4: RAS, 9/13 versus non-RAS, 3/11) and more frequent progression after treatment (RAS, 10/13 versus non-RAS, 2/11). Lesions with Kirsten rat sarcoma viral oncogene PVs infiltrated more tissue layers compared with the other PVs including other RAS PVs (multiple tissue layers: Kirsten rat sarcoma viral oncogene, 8/10 versus other PVs, 6/19). CONCLUSIONS: This comparison of patients with various PVs in genes of the RAS/MAPK pathway provides potential associations with certain morphological and clinical phenotypes. RAS variants were associated with more aggressive phenotypes, generating preliminary data and hypothesis for future larger studies.
Proto-Oncogene Proteins p21(ras) , Vascular Malformations , Humans , Cohort Studies , Genetic Association Studies , Mitogen-Activated Protein Kinases/genetics , Mutation , Vascular Malformations/genetics
BACKGROUND: To investigate the capacity of 99mTc-labeled 1-thio-ß-D-glucose (1-TG) and 5-thio-D-glucose (5-TG) to act as a marker for glucose consumption in tumor cells in vivo as well as to evaluate the biodistribution of 1-TG and 5-TG. We investigated the biodistribution, including tumor uptake, of 1-TG and 5-TG at various time points after injection (0.5, 2 and 4 h) in human colorectal carcinoma (HCT-116) and human lung adenocarcinoma (A549) xenograft bearing nude mice (N = 4 per tracer and time point). RESULTS: Ex vivo biodistribution studies revealed a moderate uptake with a maximum tumor-to-muscle ratio of 4.22 ± 2.7 and 2.2 ± 1.3 (HCT-116) and of 3.2 ± 1.1 and 4.1 ± 1.3 (A549) for 1-TG and 5-TG, respectively, with a peak at 4 h for 1-TG and 5-TG. Biodistribution revealed a significantly higher uptake compared to blood in kidneys (12.18 ± 8.77 and 12.69 ± 8.93%ID/g at 30 min) and liver (2.6 ± 2.8%ID/g) for 1-TG and in the lung (7.24 ± 4.1%ID/g), liver (6.38 ± 2.94%ID/g), and kidneys (4.71 ± 1.97 and 4.81 ± 1.91%ID/g) for 5-TG. CONCLUSIONS: 1-TG and 5-TG showed an insufficient tumor uptake with a moderate tumor-to-muscle ratio, not reaching the levels of commonly used tracer, for diagnostic use in human colorectal carcinoma and human lung adenocarcinoma xenograft model.
Background & Aims: Herein we used data derived from the SORAMIC trial to explore the predictive value of systemic inflammatory markers (neutrophil-to-lymphocyte ratio [NLR] and platelet-to-lymphocyte ratio [PLR]) in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib monotherapy or the combination of selective internal radiation therapy (SIRT)/sorafenib. Methods: Patients randomized to sorafenib monotherapy or SIRT/sorafenib within the per-protocol population of the SORAMIC trial were evaluated in this exploratory post hoc analysis. The median baseline values of NLR and PLR were used as cut-off values to describe subgroups. Kaplan-Meier curves with log-rank tests were used to evaluate median survival in the sorafenib and SIRT/sorafenib arms in each subgroup. Multivariable Cox regression analysis was applied to eliminate the effect of confounding factors. Results: A total of 275 patients with a median overall survival of 12.4 months were included in this analysis. The median NLR value of the cohort was 2.77 and the median PLR was 26.5. There was no significant difference in overall survival between the sorafenib and SIRT/sorafenib arms in patients with low NLR (p = 0.72) and PLR (p = 0.35) values. In patients with high NLR values, there was no statistically significant difference in median overall survival between SIRT/sorafenib and sorafenib cohorts (12.1 vs. 9.2 months, p = 0.21). In patients with high PLR values, overall survival in the SIRT/sorafenib arm was significantly longer than in the sorafenib arm (15.9 vs. 11.0 months, p = 0.029). This significant difference was preserved in the multivariable analysis (SIRT/sorafenib arm: hazard ratio 0.65, 95% CI 0.44-0.96, p = 0.03) incorporating age, Child-Pugh grade, and alpha-fetoprotein levels. Conclusions: PLR is a potential predictive factor of benefit from additional SIRT in patients with HCC receiving sorafenib therapy. The potential predictive value of PLR should be further evaluated in future trials. Impact and implications: Systemic therapies are the mainstay of treatment in patients with hepatocellular carcinoma at advanced stages. However, not all patients respond well to these treatments. In our analysis, using blood test parameters showing systemic inflammation status, we were able to identify patients who would benefit more from combined treatment with a locoregional treatment of radioembolization (or selective internal radiation therapy).
OBJECTIVES: To compare clinical success, procedure time, and complication rates between MRI-guided and CT-guided real-time biopsies of small focal liver lesions (FLL) < 20 mm. METHODS: A comparison of a prospectively collected MRI-guided cohort (n = 30) to a retrospectively collected CT-guided cohort (n = 147) was performed, in which patients underwent real-time biopsies of small FLL < 20 mm in a freehand technique. In both groups, clinical and periprocedural data, including clinical success, procedure time, and complication rates (classified according to CIRSE guidelines), were analyzed. Wilcoxon rank sum test, Pearson's chi-squared test, and Fisher's exact test were used for statistical analysis. Additionally, propensity score matching (PSM) was performed using the following criteria for direct matching: age, gender, presence of liver cirrhosis, liver lobe, lesion diameter, and skin-to-target distance. RESULTS: The median FLL diameter in the MRI-guided cohort was significantly smaller compared to CT guidance (p < 0.001; 11.0 mm vs. 16.3 mm), while the skin-to-target distance was significantly longer (p < 0.001; 90.0 mm vs. 74.0 mm). MRI-guided procedures revealed significantly higher clinical success compared to CT guidance (p = 0.021; 97% vs. 79%) as well as lower complication rates (p = 0.047; 0% vs. 13%). Total procedure time was significantly longer in the MRI-guided cohort (p < 0.001; 38 min vs. 28 min). After PSM (n = 24/n = 38), MRI-guided procedures still revealed significantly higher clinical success compared to CT guidance (p = 0.039; 96% vs. 74%). CONCLUSION: Despite the longer procedure time, freehand biopsy of small FLL < 20 mm under MR guidance can be considered superior to CT guidance because of its high clinical success and low complication rates. CLINICAL RELEVANCE STATEMENT: Biopsy of small liver lesions is challenging due to the size and conspicuity of the lesions on native images. MRI offers higher soft tissue contrast, which translates into a higher success of obtaining enough tissue material with MRI compared to CT-guided biopsies. KEY POINTS: ⢠Image-guided biopsy of small focal liver lesions (FLL) is challenging due to inadequate visualization, leading to sampling errors and false-negative biopsies. ⢠MRI-guided real-time biopsy of FLL < 20 mm revealed significantly higher clinical success (p = 0.021; 97% vs. 79%) and lower complication rates (p = 0.047; 0% vs. 13%) compared to CT guidance. ⢠Although the procedure time is longer, MRI-guided biopsy can be considered superior for small FLL < 20 mm.
Background Coronary CT angiography is a first-line test in coronary artery disease but is limited by severe calcifications. Photon-counting-detector (PCD) CT improves spatial resolution. Purpose To investigate the effect of improved spatial resolution on coronary stenosis assessment and reclassification. Materials and Methods Coronary stenoses were evaluated prospectively in a vessel phantom (in vitro) containing two stenoses (25%, 50%), and retrospectively in patients (in vivo) who underwent ultrahigh-spatial-resolution cardiac PCD CT (from July 2022 to April 2023). Images were reconstructed at standard resolution (section thickness, 0.6 mm; increment, 0.4 mm; Bv44 kernel), high spatial resolution (section thickness, 0.4 mm; increment, 0.2 mm; Bv44 kernel), and ultrahigh spatial resolution (section thickness, 0.2; increment, 0.1 mm; Bv64 kernel). Percentages of diameter stenosis (DS) were compared between reconstructions. In vitro values were compared with the manufacturer specifications of the phantom and patient results were assessed regarding effects on Coronary Artery Disease Reporting and Data System (CAD-RADS) reclassification. Results The in vivo sample included 114 patients (mean age, 68 years ± 9 [SD]; 71 male patients). In vitro percentage DS measurements were more accurate with increasing spatial resolution for both 25% and 50% stenoses (mean bias for standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 10.1%, 8.0%, and 2.3%; P < .001). In vivo results confirmed decreasing median percentage DS with increasing spatial resolution for calcified stenoses (n = 161) (standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 41.5% [IQR, 27.3%-58.2%], 34.8% [IQR, 23.7%-55.1%], and 26.7% [IQR, 18.6%-44.3%]; P < .001), whereas noncalcified (n = 13) and mixed plaques (n = 19) did not show evidence of a difference (P ≥ .88). Ultrahigh-spatial-resolution reconstructions led to reclassification of 62 of 114 (54.4%) patients to lower CAD-RADS category than that assigned using standard resolution. Conclusion In vivo and in vitro coronary stenosis assessment improved for calcified stenoses by using ultrahigh-spatial-resolution PCD CT reconstructions, leading to lower percentage DS compared with standard resolution and clinically relevant rates of reclassification. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by McCollough in this issue.
Coronary Artery Disease , Coronary Stenosis , Humans , Male , Aged , Coronary Artery Disease/diagnostic imaging , Constriction, Pathologic , Computed Tomography Angiography , Retrospective Studies , Coronary Stenosis/diagnostic imaging , Tomography, X-Ray Computed , Coronary Angiography
BACKGROUND: The aim of the study was to assess the role of diffusion-weighted imaging (DWI) to evaluate treatment response in patients with liver metastases of colorectal cancer. PATIENTS AND METHODS: In this retrospective, observational cohort study, we included 19 patients with 18 responding metastases (R-Mets; follow-up at least one year) and 11 non-responding metastases (NR-Mets; local tumor recurrence within one year) who were treated with high-dose-rate brachytherapy (HDR-BT) and underwent pre- and post-interventional MRI. DWI (qualitatively, mean apparent diffusion coefficient [ADCmean], ADCmin, intraindividual change of ADCmean and ADCmin) were evaluated and compared between pre-interventional MRI, first follow-up after 3 months and second follow-up at the time of the local tumor recurrence (in NR-Mets, mean: 284 ± 122 d) or after 12 months (in R-Mets, mean: 387+/-64 d). Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) for detection of local tumor recurrence were calculated on second follow up, evaluating (1) DWI images only, and (2) DWI with Gd-enhanced T1-weighted images on hepatobiliary phase (contrast-enhanced [CE] T1-weight [T1w] hepatobiliary phase [hb]). RESULTS: ADCmean significantly increased 3 months after HDR-BT in both groups (R-Mets: 1.48 ± 0.44 and NR-Mets: 1.49 ± 0.19 x 10-3 mm2;/s, p < 0.0001 and p = 0.01), however, intraindividual change of ADCmean (175% vs.127%, p = 0.03) and ADCmin values (0.44 ± 0.24 to 0.82 ± 0.58 x 10-3 mm2/s) significantly increased only in R-Mets (p < 0.0001 and p < 0.001). ADCmin was significant higher in R-Mets compared to NR-Mets on first follow-up (p = 0.04). Sensitivity (1 vs. 0.72), specificity (0.94 vs. 0.72), PPV (0.91 vs. 0.61) and NPV (1 vs. 0.81) could be improved by combining DWI with CE T1w hb compared to DWI only. CONCLUSIONS: DW-MRI seems to be helpful in the qualitative and quantitative evaluation of treatment response after HDR-BT of colorectal metastases in the liver.
Brachytherapy , Colorectal Neoplasms , Liver Neoplasms , Humans , Diffusion Magnetic Resonance Imaging/methods , Retrospective Studies , Brachytherapy/methods , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/radiotherapy , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/radiotherapy , Liver Neoplasms/pathology , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/radiotherapy , Colorectal Neoplasms/pathology
BACKGROUND AND PURPOSE: To determine the potential prognostic value of proliferation and angiogenesis plasma proteins following CT-guided high dose rate brachytherapy (HDR-BT) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: For this prospective study, HDR-BT (1 × 15 Gy) was administered to 24 HCC patients. Plasma was obtained and analyzed using an Olink proteomics Target-96 immuno-oncology-panel that included multiple markers of angiogenesis and proliferation. Fold-change (FC) ratios were calculated by comparing baseline and 48 h post HDR-BT paired samples. Patients were classified as responders (n = 12) if they had no local progression within 6 months or systemic progression within 2 years. Non-responders (n = 12) had recurrence within 6 months and/or tumor progression or extrahepatic disease within 2 years. RESULTS: Proliferation marker EGF was significantly elevated in non-responders compared to responders (p = 0.0410) while FGF-2, HGF, and PlGF showed no significant differences. Angiogenesis markers Angiopoietin-1 and PDGF-B were likewise significantly elevated in non-responders compared to responders (p = 0.0171, p = 0.0462, respectively) while Angiopoietin-2, VEGF-A, and VEGFR-2 did not differ significantly. Kaplan-Meier analyses demonstrated significantly shorter time to systemic progression in patients with increased EGF and Angiopoietin-1 (p = 0.0185, both), but not in patients with one of the remaining proteins elevated (all p > 0.1). Pooled analysis for these 9 proteins showed significantly shorter time to systemic progression for FC ≥1.3 and ≥1.5 for at least 3 proteins elevated (p = 0.0415, p = 0.0193, respectively). CONCLUSION: Increased plasma levels of EGF and Angiopoietin-1 after HDR-BT for HCC are associated with poor response and may therefore function as predictive biomarkers of outcome.
Lymph node metastasis (LNM) occurs in less than 5% of soft tissue sarcoma (STS) patients and indicates an aggressive course of disease. Suspicious lymph nodes (LN) in staging imaging are a frequent topic of discussion in multidisciplinary tumor boards. Predictive markers are needed to facilitate stratification and improve treatment of STS patients. In this study, 56 STS patients with radiologically suspicious and subsequently histologically examined LN were reviewed. Patients with benign (n = 26) and metastatic (n = 30) LN were analyzed with regard to clinical, laboratory and imaging parameters. Patients with LNM exhibited significantly larger short axis diameter (SAD) and long axis diameter (LAD) vs. patients with benign LN (median 22.5 vs. 14 mm, p < 0.001 and median 29.5 vs. 21 mm, p = 0.003, respectively). Furthermore, the presence of central necrosis and high maximal standardized uptake value (SUVmax) in FDG-PET-CT scans were significantly associated with LNM (60 vs. 11.5% of patients, p < 0.001 and median 8.59 vs. 3.96, p = 0.013, respectively). With systemic therapy, a slight median size regression over time was observed in both metastatic and benign LN. Serum LDH and CRP levels were significantly higher in patients with LNM (median 247 vs. 187.5U/L, p = 0.005 and 1.5 vs. 0.55 mg/dL, p = 0.039, respectively). This study shows significant associations between LNM and imaging features as well as laboratory parameters of STS patients. The largest SAD, SUVmax in FDG-PET-CT scan, the presence of central necrosis, and high serum LDH level are the most important parameters to distinguish benign from metastatic LNs.
Sarcoma , Soft Tissue Neoplasms , Humans , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18 , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Sarcoma/pathology , Soft Tissue Neoplasms/pathology , Necrosis/pathology , Retrospective Studies
OBJECTIVE: Distances and angles measured from long-leg radiographs (LLR) are important for surgical decision-making. However, projectional radiography suffers from distortion, potentially generating differences between measurement and true anatomical dimension. These phenomena are not uniform between conventional radiography (CR) digital radiography (DR) and fan-beam technology (EOS). We aimed to identify differences between these modalities in an experimental setup. MATERIALS AND METHODS: A hemiskeleton was stabilized using an external fixator in neutral, valgus and varus knee alignment. Ten images were acquired for each alignment and each modality: one CR setup, two different DR systems, and an EOS. A total of 1680 measurements were acquired and analyzed. RESULTS: We observed great differences for dimensions and angles between the 4 modalities. Femoral head diameter measurements varied in the range of > 5 mm depending on the modality, with EOS being the closest to the true anatomical dimension. With functional leg length, a difference of 8.7% was observed between CR and EOS and with the EOS system being precise in the vertical dimension on physical-technical grounds, this demonstrates significant projectional magnification with CR-LLR. The horizontal distance between the medial malleoli varied by 20 mm between CR and DR, equating to 21% of the mean. CONCLUSIONS: Projectional distortion resulting in variations approaching 21% of the mean indicate, that our confidence on measurements from standing LLR may not be justified. It appears likely that among the tested equipment, EOS-generated images are closest to the true anatomical situation most of the time.
BACKGROUND: Chest radiographs (CXRs) are still of crucial importance in primary diagnostics, but their interpretation poses difficulties at times. RESEARCH QUESTION: Can a convolutional neural network-based artificial intelligence (AI) system that interprets CXRs add value in an emergency unit setting? STUDY DESIGN AND METHODS: A total of 563 CXRs acquired in the emergency unit of a major university hospital were retrospectively assessed twice by three board-certified radiologists, three radiology residents, and three emergency unit-experienced nonradiology residents (NRRs). They used a two-step reading process: (1) without AI support (woAI); and (2) with AI support (wAI) providing additional images with AI overlays. Suspicion of four suspected pathologies (pleural effusion, pneumothorax, consolidations suspicious for pneumonia, and nodules) was reported on a five-point confidence scale. Confidence scores of the board-certified radiologists were converted into four binary reference standards (RFS I-IV) of different sensitivities. Performance by radiology residents and NRRs woAI/wAI were statistically compared by using receiver-operating characteristics (ROCs), Youden statistics, and operating point metrics derived from fitted ROC curves. RESULTS: NRRs could significantly improve performance, sensitivity, and accuracy wAI in all four pathologies tested. In the most sensitive RFS IV, NRR consensus improved the area under the ROC curve (mean, 95% CI) in the detection of the time-critical pathology pneumothorax from 0.846 (0.785-0.907) woAI to 0.974 (0.947-1.000) wAI (P < .001), which represented a gain of 30% in sensitivity and 2% in accuracy (while maintaining an optimized specificity). The most pronounced effect was observed in nodule detection, with NRR wAI improving sensitivity by 53% and accuracy by 7% (area under the ROC curve woAI, 0.723 [0.661-0.785]; wAI, 0.890 [0.848-0.931]; P < .001). The RR consensus wAI showed smaller, mostly nonsignificant gains in performance, sensitivity, and accuracy. INTERPRETATION: In an emergency unit setting without 24/7 radiology coverage, the presented AI solution features an excellent clinical support tool to nonradiologists, similar to a second reader, and allows for a more accurate primary diagnosis and thus earlier therapy initiation.
OBJECTIVE: To investigate the effects of simultaneous cortisol cosecretion (CCS) on body composition in computed tomography (CT)-imaging and metabolic parameters in patients with primary aldosteronism (PA) with the objective of facilitating early detection. DESIGN: Retrospective cohort study. PATIENTS: Forty-seven patients with PA and CCS confirmed by 1-mg dexamethasone suppression test (DST) with a cutoff of ≥1.8 µg/dL were compared with PA patients with excluded CCS (non-CCS, n = 47) matched by age and sex. METHODS: Segmentation of the fat compartments and muscle area at the third lumbar region was performed on non-contrast-enhanced CT images with dedicated segmentation software. Additionally, liver, spleen, pancreas and muscle attenuation were compared between the two groups. RESULTS: Mean cortisol after DST was 1.2 µg/dL (33.1 nmol/L) in the non-CCS group and 3.2 µg/dL (88.3 nmol/L) in the CCS group with mild autonomous cortisol excess (MACE). No difference in total, visceral and subcutaneous fat volumes was observed between the CCS and non-CCS group (p = .7, .6 and .8, respectively). However, a multivariable regression analysis revealed a significant correlation between total serum cholesterol and results of serum cortisol after 1-mg DST (p = .026). Classification of the patients based on visible lesion on CT and PA-lateralization via adrenal venous sampling also did not show any significant differences in body composition. CONCLUSION: MACE in PA patients does not translate into body composition changes on CT-imaging. Therefore, early detection of concurrent CCS in PA is currently only attainable through biochemical tests. Further investigation of the long-term clinical adverse effects of MACE in PA is necessary.
Hydrocortisone , Hyperaldosteronism , Humans , Retrospective Studies , Body Composition , Tomography, X-Ray Computed/methods
BACKGROUND: To compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies. METHODS: Twenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL). RESULTS: Mebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046). CONCLUSION: LSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99mTc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE. RELEVANCE STATEMENT: MRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction. KEY POINTS: ⢠Both MRI and HBS can assess liver function after RE. ⢠Liver enhancement on MRI correlates with mebrofenin uptake on HBS. ⢠MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction.
Aniline Compounds , Gadolinium DTPA , Glycine , Liver Neoplasms , Radiopharmaceuticals , Humans , Prospective Studies , Radionuclide Imaging , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/radiotherapy , Magnetic Resonance Imaging/methods , Pentetic Acid , Hypertrophy
BACKGROUND: Radiological age assessment using reference studies is inherently limited in accuracy due to a finite number of assignable skeletal maturation stages. To overcome this limitation, we present a deep learning approach for continuous age assessment based on clavicle ossification in computed tomography (CT). METHODS: Thoracic CT scans were retrospectively collected from the picture archiving and communication system. Individuals aged 15.0 to 30.0 years examined in routine clinical practice were included. All scans were automatically cropped around the medial clavicular epiphyseal cartilages. A deep learning model was trained to predict a person's chronological age based on these scans. Performance was evaluated using mean absolute error (MAE). Model performance was compared to an optimistic human reader performance estimate for an established reference study method. RESULTS: The deep learning model was trained on 4,400 scans of 1,935 patients (training set: mean age = 24.2 years ± 4.0, 1132 female) and evaluated on 300 scans of 300 patients with a balanced age and sex distribution (test set: mean age = 22.5 years ± 4.4, 150 female). Model MAE was 1.65 years, and the highest absolute error was 6.40 years for females and 7.32 years for males. However, performance could be attributed to norm-variants or pathologic disorders. Human reader estimate MAE was 1.84 years and the highest absolute error was 3.40 years for females and 3.78 years for males. CONCLUSIONS: We present a deep learning approach for continuous age predictions using CT volumes highlighting the medial clavicular epiphyseal cartilage with performance comparable to the human reader estimate.
