Annalaura Salerno

Systemic pentraxin-3 levels reflect vascular enhancement and progression in Takayasu arteritis

IntroductionProgression of arterial involvement is often observed in patients with Takayasu arteritis (TA) thought to be in remission. This reflects the failure of currently used biomarkers and activity criteria to detect smouldering inflammation occurring within arterial wall. Pentraxin-3 (PTX3) is a soluble pattern recognition receptor produced at sites of inflammation and could reveal systemic as well as localized inflammatory processes. We verified whether the blood concentrations of PTX3 and of C-reactive protein (CRP) in patients with Takayasu arteritis (TA) might reflect vascular wall involvement, as assessed by signal enhancement after contrast media administration, and the progression of arterial involvement.MethodsA cross-sectional single-centre study was carried out on 42 patients with TA that comprised assessment of PTX3, of CRP and erythrocyte sedimentation velocity (ESR). In total, 20 healthy controls and 20 patients with Systemic Lupus Erythematous (SLE) served as controls. Vascular imaging was carried out by magnetic resonance angiography, doppler ultrasonography and computed tomography angiography.ResultsPatients with TA and SLE had higher plasmatic PTX3 and CRP concentrations than healthy controls (P = 0.009 and 0.017, respectively). PTX3 levels did not correlate with those of CRP. Patients with active systemic TA had significantly higher concentrations of CRP but similar levels of PTX3 than patients with quiescent disease. In contrast, patients with vascular inflammation detectable at imaging had higher PTX3 concentrations (P = 0.016) than those in which vessel inflammation was not evident, while CRP levels were similar. The concentration of PTX3 but not that of CRP was significantly higher in TA patients with worsening arterial lesions that were not receiving antagonists of tumor necrosis factor-? or interleukin-6.ConclusionsArterial inflammation and progression of vascular involvement influence plasma PTX3 levels in TA, while levels of CRP accurately reflect the burden of systemic inflammation. These results support the contention that PTX3 reflects different aspects of inflammation than CRP and might represent a biomarker of actual arteritis in TA.

Gastric cancer: texture analysis from multidetector computed tomography as a potential preoperative prognostic biomarker

ObjectivesTo investigate the association between preoperative texture analysis from multidetector computed tomography (MDCT) and overall survival in patients with gastric cancer.MethodsInstitutional review board approval and informed consent were obtained. Fifty-six patients with biopsy-proved gastric cancer were examined by MDCT and treated with surgery. Image features from texture analysis were quantified, with and without filters for fine to coarse textures. The association with survival time was assessed using Kaplan–Meier and Cox analysis.ResultsThe following parameters were significantly associated with a negative prognosis, according to different thresholds: energy [no filter] – Logarithm of relative risk (Log RR): 3.25; p = 0.046; entropy [no filter] (Log RR: 5.96; p = 0.002); entropy [filter 1.5] (Log RR: 3.54; p = 0.027); maximum Hounsfield unit value [filter 1.5] (Log RR: 3.44; p = 0.027); skewness [filter 2] (Log RR: 5.83; p = 0.004); root mean square [filter 1] (Log RR: - 2.66; p = 0.024) and mean absolute deviation [filter 2] (Log RR: - 4.22; p = 0.007).ConclusionsTexture analysis could increase the performance of a multivariate prognostic model for risk stratification in gastric cancer. Further evaluations are warranted to clarify the clinical role of texture analysis from MDCT.Key points• Textural analysis from computed tomography can be applied in gastric cancer.• Preoperative non-invasive texture features are related to prognosis in gastric cancer.• Texture analysis could help to evaluate the aggressiveness of this tumour.

Prognostic role of diffusion-weighted MR imaging for resectable gastric cancer

PURPOSE To prospectively investigate the role of apparent diffusion coefficient (ADC) calculated from diffusion-weighted magnetic resonance (MR) imaging as a potential prognostic biomarker in the evaluation of the aggressiveness of gastric cancer. MATERIALS AND METHODS This prospective study had institutional review board approval. Informed consent was obtained from all patients. Between October 2009 and December 2013, a total of 99 patients (65 men, 34 women; mean age, 62.02 years; age range, 32.33-85.15 years) with biopsy-proved cancer (28 esophagogastric junction and 71 gastric cancers) were examined with a 1.5-T MR imaging system, including T1-, T2-, and diffusion-weighted sequences. ADC measurements were obtained. Seventy-one patients were directly treated with surgery, while 28 underwent neoadjuvant chemotherapy beforehand. Pathologic ADC, pathologic T and N stages, tumor location, surgical approach, and histologic subtype were investigated with univariate and multivariate analyses by using the Cox regression model. RESULTS At a total median follow-up period of 21 months, 31 patients had died. The median follow-up was 25 months for the surgery-only group (19 of 31 events [61%]) and 28 months for the chemotherapy group (12 of 31 events [39%]). In the multivariate analysis, ADC values of 1.5 × 10(-3) mm(2)/sec or lower were associated with a negative prognosis, both in the total population (log-relative risk, 1.73; standard error, 0.56; P = .002) and in the surgery-only (log-relative risk, 1.97; standard error, 0.66; P = .003) and chemotherapy (log-relative risk, 2.93; standard error, 1.41; P = .03) groups, along with other significant prognostic factors (in particular, pathologic T and N stages). CONCLUSION Pathologic ADC represents a strong independent prognostic factor in the evaluation of the aggressiveness of gastric cancer, in addition to clinical and surgical variables.

Chromogranin-A production and fragmentation in patients with Takayasu arteritis

BackgroundChromogranin-A (CgA) is a secretory protein processed into peptides that regulate angiogenesis and vascular cells activation, migration and proliferation. These processes may influence arterial inflammation and remodelling in Takayasu arteritis (TA).MethodsPlasma levels of full-length CgA (CgA439), CgA fragments lacking the C-terminal region (CgA-FRs) and the N-terminal fragment, CgA1–76 (vasostatin-1, VS-1) were analysed in 42 patients with TA and 20 healthy age-matched controls. Vascular remodelling was longitudinally assessed by imaging. CgA peptides were related to markers of systemic and local inflammation, disease activity and vascular remodelling.ResultsLevels of CgA-FRs and VS-1 were increased in TA. Treatment with proton-pump inhibitors (PPIs) and arterial hypertension partially accounted for CgA levels and high inter-patient variability. CgA439, CgA-FRs and VS-1 levels did not reflect disease activity or extent. Markers of systemic or local inflammation correlated with higher CgA-FRs and VS-1 in normotensive patients and with higher CgA439 in hypertensive patients. Treatment with non-biologic anti-rheumatic agents was associated with increased CgA-FRs and a distinctive regulation of CgA processing. Reduced blood levels of anti-angiogenic CgA peptides were associated with vascular remodelling in the groups of patients on PPIs and with arterial hypertension.ConclusionsThe plasma levels of CgA fragments are markedly increased in TA as a consequence of disease- and therapy-related variables. Anti-angiogenic forms of CgA may limit vascular remodelling. Given the effect of the various CgA peptides, it is advisable to limit the therapeutic prescriptions that might influence CgA-derived peptide levels to clearly agreed medical indications until further data become available.

Pre-treatment MDCT-based texture analysis for therapy response prediction in gastric cancer: Comparison with tumour regression grade at final histology

PURPOSE An accurate prediction of tumour response to therapy is fundamental in oncology, so as to prompt personalised treatment options if needed. The aim of this study was to investigate the ability of preoperative texture analysis from multi-detector computed tomography (MDCT) in the prediction of the response rate to neo-adjuvant therapy in patients with gastric cancer. MATERIAL AND METHODS Thirty-four patients with biopsy-proven gastric cancer were examined by MDCT before neo-adjuvant therapy, and treated with radical surgery after treatment completion. Tumour regression grade (TRG) at final histology was also assessed. Image features from texture analysis were quantified, with and without filters for fine to coarse textures. Patients with TRG 1-3 were considered responders while TRG 4-5 as non- responders. The response rate to neo-adjuvant therapy was assessed both at univariate and multivariate analysis. RESULTS Fourteen parameters were significantly different between the two subgroups at univariate analysis; in particular, entropy and compactness (higher in responders) and uniformity (lower in responders). According to our model, the following parameters could identify non-responders at multivariate analysis: entropy (≤6.86 with a logarithm of Odds Ratio - Log OR -: 4.11; p=0.003); range (>158.72; Log OR: 3.67; p=0.010) and root mean square (≤3.71; Log OR: 4.57; p=0.005). Entropy and three-dimensional volume were not significantly correlated (r=0.06; p=0.735). CONCLUSION Pre-treatment texture analysis can potentially provide important information regarding the response rate to neo-adjuvant therapy for gastric cancer, improving risk stratification.

SAT0350 Functional Characterisation of Takayasu Arteritis Vascular Lesions by MR and FDG-PET/CT Provides Non-Redundant Information over Clinical Assessment

Background Disease activity (DA) assessment in Takayasu arteritis (TA) is an unresolved enigma as systemic inflammation and current activity measures poorly correlate with arterial progression. Morphological imaging, e.g. with morphological magnetic resonance (MR) sequencies, is the goal standard to evaluate arterial progression after its occurrence, and it is not clear whether functional characterisation of the lesions (e.g. contrast enhancement at MR or fluorodesoxyglucose [FDG] uptake at FDG-PET/CT [PET]) can predict arterial progression before its occlusion. We are prospectively following 60 TA patients with functional and morphological imaging to understand the predictors of arterial progression. Here we present the baseline assessment of the first 47 patients. Objectives to verify if activity measures, and functional lesion characterisation with PET or MR provide independent information. Methods Cross-sectional analysis of 47 TA patients according to ACR criteria followed at our Institution and undergoing closely related MR, PET and clinical evaluation. DA was evaluated with NIH criteria, indian Takayasu activity score (ITAS2010) and physician global assessment (PGA). At MR, arterial lesions were characterized by length, thickness and percentage of stenosis. Contrast to noise ratio (CNR) was calculated, when technically possible. Each vascular lesion uptake large enough to be evaluated by PET was evaluated with a quantitative (SUVmax) method. Per patients and per lesion analyses were performed. Results The median interval between MR and PET was 24 days. TA was active in 25, 17 and 35 patients according to NIH criteria, ITAS2010 and PGA (including active and grumbling disease). In total, MR identified 333 arterial lesions (median lesion N per patient 6, IQR 1–15). At the “per patient” analysis, median CNRmax at MR was 12,43 (IQR 0,00–54,29). CNRmax did not correlate with acute-phase markers nor activity measures, except for ITAS-CRP (rho 0.300, p=0,038). PET showed significant uptake in 18 patients. Meadian SUVmax was 1,19 (IQR 0,00–9,00). SUVmax did not correlate with activity measures. At the “per lesions” analysis, 56 lesions had positive uptake in PET. There was no correlation between the degree of enhancement at MR and of FDG uptake at PET (rho 0,094, p=0,529). Conclusions Current activity measures, mainly based on systemic inflammation, and functional characterisation of the arterial lesions by MR and FDG-PET provide independent information in TA. The prospective part of this study will clarify the clinical relevance and the predictive values for progression of these different pieces of information. Disclosure of Interest None declared