Massimiliano Casali

Rituximab therapy for chronic periaortitis

Chronic periaortitis (CP) is a rare condition, hallmarked by periaortic fibro-inflammatory tissue which often causes ureteral obstruction, and encompasses idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm (IAAA). CP usually responds to glucocorticoids, but some patients may be steroid-refractory or not tolerate standard glucocorticoid doses. For such cases, valid therapeutic alternatives are lacking.1 2 Combinations of prednisone and immunosuppressants (eg, cyclophosphamide, mycophenolate mofetil) are not of proven superiority to prednisone alone, and their effectiveness in refractory CP is unknown.3 4 Because B cells abundantly infiltrate CP lesions,5 and CP is often associated with autoimmune diseases,6 we used rituximab in two patients with CP, one refractory to conventional treatments, and the other with contraindications to standard-dose glucocorticoids. Our first patient, a 49-year-old woman, was hospitalised for malaise and back pain. Abdominal CT revealed a soft-tissue-density periaortic mass suggesting CP, a diagnosis confirmed by laparoscopic biopsy (figure 1). The patient responded to prednisone (initial dose, 1 mg/kg/day), with symptom remission and reduction in CP thickness, but relapsed with back pain and CP enlargement when the prednisone dose was 5 mg/day (8 months after treatment initiation). …

Contrast-enhanced ultrasound of the carotid artery in patients with large vessel vasculitis: Correlation with positron emission tomography findings.

To assess the findings of contrast‐enhanced ultrasound (CEUS) of carotid arteries in patients with large vessel vasculitis (LVV) and to compare them with those observed using 18F‐fluorodeoxyglucose–positron emission tomography (18FDG‐PET).

PET and PET/CT with 68Gallium-Labeled Somatostatin Analogues in Non GEP-NETs Tumors

Somatostatin (SST) is a 28-amino-acid cyclic neuropeptide mainly secreted by neurons and endocrine cells. A major interest for SST receptors (SSTR) as target for in vivo diagnostic and therapeutic purposes was born since a series of stable synthetic SST-analouges PET became available, being the native somatostatin non feasible for clinical use due to the very low metabolic stability. The rationale for the employment of SST-analogues to image cancer is both based on the expression of SSTR by tumor and on the high affinity of these compounds for SSTR. The primary indication of SST-analogues imaging is for neuroendocrine tumors (NETs), which usually express a high density of SSTR, so they can be effectively targeted and visualized with radiolabeled SST-analogues in vivo. Particularly, SST-analogues imaging has been widely employed in gastroenteropancreatic (GEP) NETs. Nevertheless, a variety of tumors other than NETs expresses SSTR thus SST-analogues imaging can also be used in these tumors, particularly if treatment with radiolabeled therapeutic SST-analouges PET is being considered. The aim of this paper is to provide a concise overview of the role of positron emission tomography/computed tomography (PET/CT) with 68Ga-radiolabeled SST-analouges PET in tumors other than GEP-NETs.

The Role of Imaging in the Diagnosis of Recurrence of Primary Seminal Vesicle Adenocarcinoma

Primary seminal vesicle (SV) adenocarcinoma is a rare tumor. A small amount of data about the role of imaging to detect tumor recurrence is available. We report the case of a 58-year-old patient with primary SV clear-cell well-differentiated adenocarcinoma. Clinical and instrumental examinations were negative for the 32 months after treatments when computed tomography scan, [18F]fluoro-D-glucose positron emission tomography/computed tomography and pelvic magnetic resonance imaging showed the appearance of a lesion in the left perineal muscle suspected for recurrence. Patient was symptomless. Cytology of the suspected lesion confirmed SV adenocarcinoma recurrence. The combined approach, using radiological and nuclear medicine techniques, seems to be effective in the follow-up of SV adenocarcinoma. Technological advances, together with awareness of this rare tumor, have the potential of improving patients outcomes not only by providing earlier detection and accurate staging, but also by detecting recurrence and thereby avoiding delays and therapeutic dilemmas.

Aortic Dilatation in Patients with Large Vessel Vasculitis: a Longitudinal Case Control Study Using PET/CT

OBJECTIVE To evaluate aortic diameter and predictors of aortic dilatation using 18FDG-PET/CT in a longitudinally followed cohort of patients with large vessel vasculitis (LVV) compared with controls. METHODS All consecutive patients with LVV who underwent at least 2 PET/CT scans between January 2008 and May 2015 were included. The first and last PET/CT study was evaluated by a radiologist and a nuclear medicine physician. Diameter and FDG uptake of the aorta was measured at 4 different levels: ascending, descending thoracic, suprarenal and infrarenal abdominal aorta. Twenty-nine age- and sex-matched patients with lymphoma who underwent at least 2 PET/CT scans in the same time interval were selected as controls. RESULTS 93 patients with LVV were included in the study. In the time interval between first and last PET/CT study (median time 31 months), the diameter of the ascending, descending thoracic and suprarenal abdominal aorta significantly increased in LVV patients but not in controls. At last PET/CT, patients with LVV compared with controls had higher diameter of ascending [35.41 (5.54) vs 32.97 (4.11) mm, p = 0.029], descending thoracic [28.42 (4.82) vs 25.72 (3.55) mm, p = 0.007] and suprarenal abdominal aorta, mean [25.34 (7.01) vs 22.16 (3.26) mm, p = 0.005] and more frequently had aortic dilatation [19% vs 3%, p = 0.023]. Significant predictors of aortic dilatation were male sex [OR 7.27, p = 0.001] and, only for GCA, hypertension [OR 6.30, p = 0.031]. Finally, GCA patients with aortic FDG uptake grade 3 at first PET/CT, compared to those with aortic FDG uptake ≤2, had significantly higher aortic diameter. CONCLUSIONS Patients with LVV are at increased risk of aortic dilatation compared with age- and sex-matched controls. Significant predictors of aortic dilatation are male sex and, only for GCA, hypertension. GCA patients with aortic FDG uptake grade 3 are at increased risk of aortic dilatation.

Radiolabeled Somatostatin Analogues in the Treatment of Non-GEP-NET Tumors

In the last two decades Peptide Receptor Radionuclide Therapy (PRRT) has acquired great importance as an alternative or complementary tool in the treatment of neuroendocrine tumors (NETs) and other somatostatin receptor (SSTR) positive tumors. Many experiences of PRRT using different radiopharmaceuticals, mainly beta-emitters 90Yttrium (90Y) and 177Lutetium (177Lu) labeled peptides, are reported in the literature with encouraging results in terms of tumor regression, self-assessed quality of life, and overall survival. SSTRs are mainly expressed in Gastro-Entero-Pancreatic neuroendocrine tumors (GEP-NETs) but in many other neoplasms (NETs and non-NETs) it is possible to find a high SSTR expression. Some of these are pheochromocytoma/paraganglioma, bronchial NET, thymic NET, meningioma, thyroid cancer (differentiated and medullary) and Merkel cell carcinoma.

SAT0340 Distinct Distribution Patterns of Large Vessel Vasculitis Assessed with 18f-FDG PET/CT: A Cluster and Principal Component Analysis Study

Background The interpretation of data from 18F-FDG PET/CT studies on large vessel vasculitis (LVV) is difficult due to the scarcity of studies and to the heterogeneity of LVV populations examined. In the absence of gold standard parameters for the assessment of LVV arterial inflammation, there is a great need to develop analytical methodologies useful to properly exploit the information derived from such studies. Principal component analysis (PCA) and cluster analysis (CA) have not yet been applied to explore the LVV distribution patterns, assessed by 18F-FDG PET/CT. Objectives The aim of our study was to investigate whether PCA and CA are useful methods in identifying distinct distribution patterns of LVV, according to the specific diagnostic entity examined (giant cell arteritis, GCA; Takayasus arteritis, TAK). Methods A total of 130 18F-FDG PET/CT studies have been retrospectively examined by a nuclear physician blinded to clinical data. Maximum standardized uptake values (SUVmax) in 14 vascular districts including aortic segments (ascending aorta, thoracic aorta, aortic arch, discending thoracic aorta and abdominal aorta) and the main tributaries (carotid, subclavian, axillary, iliac and femoral arteries) have been measured and transformed into Z-scores. Identification of distribution patterns of vascular involvement has been performed using PCA and agglomerative hierarchical CA (SPSS Statistics, version 22nd). Results Three groups of vascular districts with similar trends in terms of standardized SUVmax have been identified: epiaortic arteries; aortic arch and ascending aorta; descending and abdominal aorta, with iliac and femoral arteries. A component including the entire aortic district was identified in TAK group, but not in GCA group. Conclusions PCA and CA approach revealed a subtle skewing in terms of distribution patterns of arterial involvement between TAK and GCA, assessed by 18F-FDG PET/CT SUVmax values. The influence of atherosclerosis and immunosenescence on the different trends in the aorta districts of TAK and GCA needs to be further elucidated. References Grayson PC, et al. Distribution of arterial lesions in Takayasus arteritis and giant cell arteritis. Ann Rheum Dis 2012;71:1329–1334. Arnaud L, et al. Cluster analysis of arterial involvement in Takayasu arteritis reveals symmetric extension of the lesions in paired arterial beds. Arthritis Rheum 2011;63:1136–40. Disclosure of Interest None declared

AB0051 Angiogenic and Anti-Angiogenic Factors: Biomarkers for Large Vessel Vasculitis?

Background Large vessel vasculitides (LVV) – Takayasu Arteritis (TA) and Giant Cell Arteritis (GCA) are inflammatory diseases of the aorta and its main branches. A cytokine cluster involving the IL-6 – IL-17 axis as well as another one centring on the IL-12-IFN-γ axis are involved in LVV pathogenesis. (1) Disease activity could be evaluated by measuring ESR and CRP as well as by using imaging techniques (Doppler Ultrasound, Computed Tomography scan, Magnetic Resonance Imaging or Positron Emission Tomography scan – CT/PET) and specific scoring systems (IndianTakayasus Arteritis Activity Score - ITAS and Kerr/National Institutes of Health index - Kerr/NIH). To date, angiogenic factors have been evaluated but specific biomarkers for disease activity are still lacking (2) Objectives The aim of our study was to evaluate angiogenic and anti-angiogenic factor expression in LVV, in order to evaluate their role as biomarkers. Methods We enrolled 67 patients with LVV [TA (40, 59.7%) or GCA (27, 40.3%)] and 50 Normal Controls (NC). Angiogenic (angiopoietin-1, angiopoietin-2, Fibroblast Growth Factor2 – FGF-2, Vascular Cell Adesion Molecule1 – VCAM-1, Vascular Endothelial Growth Factor – VEGF) and anti-angiogenic (angiostatin, Endostatin-1, Pentraxin 3 – PTX3) factors were analysed using enzyme-linked immuno-sorbent assay (ELISA). Disease activity was evaluated according to Kerr (≥2) and ITAS (≥1) scores, only 47 (70.1%) patients underwent CT/PET. Serum levels of angiogenic and anti-angiogenic factors were compared among active LVV, inactive LVV and NCs. When evaluating disease activity according to CT/PET, it was considered active if SUV >2. Statistical analysis was performed utilizing Mann Whitney, Kruskal Wallis for multiple comparison and Dunns post hoc test, using Graph Pad Prism software. Results No significant differences were found between LVV and NCs in angiogenic factors. Conversely, anti-angiogenic factors were all significantly increased in LVV (both GCA and TA) in comparison with NCs (angiostatin: TA vs NC, p<0.0001; GCA vs NC, p=0.0008; endostatin: TA vs NC, p=0.0002; GCA vs NC, p=0.001; PTX-3: TA vs NC, p<0.0002; GCA vs NC, p=0.001). Stratifying patients according to disease activity (with Kerr and Itas scoring systems, as well as taking into account CT/PET), no significant differences were found in angiogenic factors. Anti-angiogenic factors were significantly higher both in active LVV and inactive LVV compared with NCs (p<0.05). Conclusions Our data show an imbalance between angiogenic and anti-angiogenic factor levels in serum. No disease activity related changes were observed for these factors. References Weyand CM, Goronzy JJ. Immune mechanisms in medium and large-vessel vasculitis. Nat Rev Rheumatol 2013;9:731–740; Villa I, Bilbao MA, Martìnez-Taboada VM. Advances in the diagnosis of large vessel vasculitis: identification of biomarkers and imaging studies. Rheumatol Clin 2011;7:S22-S27 Disclosure of Interest None declared

FRI0262 The Role of 18F-FDG-PET/CT in the Diagnosis and Follow-Up of Large Vessel Vasculitis

Background PET/CT has been proposed as a useful tool to diagnose and monitor activity in the large-vessel vasculitides (LVV) giant cell arteritis (GCA) and Takayasus Arteritis (TAK), but the best approach to evaluate vascular uptake still remains debated. Both GCA and TAK often present with non-specific symptoms and laboratory test results. 18F-FDG PET/CT (PET/CT) has shown its potential to diagnose LVV earlier than any other traditional imaging techniques. Objectives The aim of this study was to investigate the role of PET/CT in assessing disease activity in patients with LVV, and to compare different semi-quantitative vascular FDG grading approaches. Methods 28 Patients with LVV underwent a total of 135 PET/CT scans and were compared to 29 matched controls. All PET/CT scans were reviewed by a nuclear physician blinded to clinical data. A semi-quantitative analysis using the maximum and mean standardized uptake value (SUVmax, SUVmean), was performed. Vascular to liver, to spleen, to blood pool, and to muscle ratios, were, respectly, determinated, to minimize the effects of time from injection to acquisition, and of blood glucose level. PET/CT findings were correlated to the clinical indices ITAS (Indian TAK activity score) and Kerr/National Institute of Health (Kerr/NIH), as well as to serum acute-phase reactants levels (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]). Results Arterial SUVmax was significantly higher in LVV (both active and inactive) patients than in controls in the following vascular districts: carotid (p 0.015-0.046), subclavian (p=0.035) arteries, thoracic (ascending, arch and descending) and abdominal aorta (p 0.0001-0.003). Arterial to liver SUVmax ratio (SUVmaxAorta-Liver ratio), arterial to spleen SUVmax ratio (SUVmaxArterial-Spleen ratio), and arterial to venous blood pool SUVmax ratio (SUVmaxArterial-Blood pool ratio) discriminated active from inactive LVV better than the arterial to muscular (gluteal) ratio (SUVmaxArterial-Muscle ratio). In particular SUVmaxAscending Aorta - Liver ratio with a cut off value of 0.65, provided a diagnostic sensitivity of 76% and a specificity of 79% (AUC =0.791). Using a cut-off value of 0.9 for the highest SUVmaxDescending Aorta - Liver ratio, it was possible to discriminate between active and inactive TAK patients with a sensitivity of 70% and a specificity of 92% (AUC =0.817). In GCA a cut-off value of 0.9 for SUVmaxAortic Arch-Spleen ratio, SUVmaxDescending Aorta-Spleen ratio, SUVmaxAortic Arch-Liver ratio, SUVmaxDescending Aorta–Liver ratio was able to discriminate active from inactive patients with a sensitivity of 70% and a specificity of 87% (AUC =0.84-0.87). Conclusions PET/CT is a useful tool for diagnosis and follow-up of LVV. In particular, SUVmaxDescending Aorta-Liver ratio in Takayasu, and SUVmaxAorta-Liver ratio, SUVmaxAorta-Spleen ratio, and SUVmaxAorta-Blood Pool ratio in GCA appeared the most useful tools in monitoring the disease activity during the follow-up. Disclosure of Interest None declared

SAT0167 Vascular Standardized Uptake Value of FDG-PET/CT Correlates with Indices of LVV Activity.

Background 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography [PET/CT] is a useful tool to diagnose large vessel vasculitis (LVV) but its role in distinguishing between active and inactive disease is still debated. Objectives To evaluate the utility of vascular standardized uptake value (SUV) assessment in differentiating between patients with clinical active and inactive LVV. Methods All patients with LVV seen in our center undergo clinical, laboratory (ESR, CRP) and imaging assessment with PET/CT scans. We retrospectively compared 14 consecutive evaluations of 12 patients with active disease according to clinical indices ITAS (Indian Takayasu activity score) and Kerr/National Institute of Health (Kerr/NIH) with 15 evaluations of 10 patients with inactive disease. ITAS, Kerr/NIH scores, ESR and CRP values were obtained within 20 days from PET/CT scans. PET/CT scans were reviewed by two nuclear medicine physicians without any clinical information. Vascular uptake was assessed using visual 4-point semiquantitative scale, vascular max SUV and vascular max SUV/liver max SUV ratio (SUV ratio) in 12 vessel segments. The highest max SUV among the different vessel segments was used for the analysis. Results Patients with active disease according to ITAS and Kerr/NIH indices compared to patients with inactive disease had higher vascular max SUV (mean ± SD 4.31 ± 1.63 vs 2.89 ± 0.99 p= 0.008) and higher SUV ratio (1.71 ± 0,74 vs 1.1 ± 0.54 p=0.016). Patients with visual grade >2 (high vascular uptake) compared to patients with visual grade <1 (low vascular uptake) had higher vascular max SUV (mean ± SD 4.62 ± 1.50 vs 2.6 ± 0.52 p< 0.0001) and SUV ratio (1.78 ± 0.78 vs 1.05 ± 0.41 p=0.004). Correlations between max SUV and ESR or CRP (r = 0.551 p = 0.002 vs. ESR; r = 0.565 p = 0.001 vs. CRP) and between SUV ratio and ESR or CRP (r = 0.522 p = 0.004 vs. ESR; r = 0.586 p = 0.001 vs. CRP) were significant. Conclusions Our results show higher values of max SUV and SUV ratio in active than in inactive LVV patients. Both max SUV and SUV ratio correlates significantly with ESR and CRP. The assessment of max SUV and SUV ratio is a promising tool in differentiating between active and inactive disease during follow-up of patients wit LVV. Disclosure of Interest None Declared