Galectin-3 interferes with tissue repair and promotes cardiac dysfunction and comorbidities in a genetic heart failure model.

Galectin-3, a biomarker for heart failure (HF), has been associated with myocardial fibrosis. However, its causal involvement in HF pathogenesis has been questioned in certain models of cardiac injury-induced HF. To address this, we used desmin-deficient mice (des-/-), a model of progressive HF characterized by cardiomyocyte death, spontaneous inflammatory responses sustaining fibrosis, and galectin-3 overexpression. Genetic ablation or pharmacological inhibition of galectin-3 led to improvement of cardiac function and adverse remodeling features including fibrosis. Over the course of development of des-/- cardiomyopathy, monitored for a period of 12 months, galectin-3 deficiency specifically ameliorated the decline in systolic function accompanying the acute inflammatory phase (4-week-old mice), whereas a more pronounced protective effect was observed in older mice, including the preservation of diastolic function. Interestingly, the cardiac repair activities during the early inflammatory phase were restored under galectin-3 deficiency by increasing the proliferation potential and decreasing apoptosis of fibroblasts, while galectin-3 absence modulated macrophage-fibroblast coupled functions and suppressed both pro-fibrotic activation of cardiac fibroblasts and pro-fibrotic gene expression in the des-/- heart. In addition, galectin-3 also affected the emphysema-like comorbid pathology observed in the des-/- mice, as its absence partially normalized lung compliance. Collectively galectin-3 was found to be causally involved in cardiac adverse remodeling, inflammation, and failure by affecting functions of cardiac fibroblasts and macrophages. In concordance with this role, the effectiveness of pharmacological inhibition in ameliorating cardiac pathology features establishes galectin-3 as a valid intervention target for HF, with additive benefits for treatment of associated comorbidities, such as pulmonary defects. Schematic illustrating top to bottom, the detrimental role of galectin-3 (Gal3) in heart failure progression: desmin deficiency-associated spontaneous myocardial inflammation accompanying cardiac cell death (reddish dashed border) is characterized by infiltration of macrophages (round cells) and up-regulation of Lgals3 (encoding secretable galectin-3, green) and detrimental macrophage-related genes (Ccr2 and Arg1). In this galectin-3-enriched milieu, the early up-regulation of profibrotic gene expression (Tgfb1, Acta2, Col1a1), in parallel to the suppression of proliferative activities and a potential of senescence induction by cardiac fibroblasts (spindle-like cells), collectively promote des-/- cardiac fibrosis and dysfunction establishing heart failure (left panel). Additionally, galectin-3+ macrophage-enrichment accompanies the development of emphysema-like lung comorbidities. In the absence of galectin-3 (right panel), the effect of macrophage-fibroblast dipole and associated events are modulated (grey color depicts reduced expression or activities) leading to attenuated cardiac pathology in the des-/-Lgals3-/- mice. Pulmonary comorbidities are also limited.

I-131 Postablation SPECT/CT Predicts Relapse of Papillary Thyroid Carcinoma more Accurately than Whole Body Scan.

BACKGROUND/AIM: The aim of the study was to prospectively compare I-131 postablation Whole Body scan (WBS) and Single Photon Emission Computerized Tomography/Computerized Tomography (SPECT/CT) scan on thyroid cancer patients. PATIENTS AND METHODS: Overall, 58 patients with papillary thyroid carcinoma were submitted to total thyroidectomy and I-131 remnant ablation. Post-ablation WBS and SPECT/CT scans performed on the same day were compared. Results of SPECT/CT were confirmed by neck and upper mediastinum ultrasound scan and on specific cases by a fully diagnostic CT scan, other tests and definitive histology acting as the gold standard. A total of 36/58 patients were followed-up for 5 years to detect relapse. RESULTS: Mac Nemar Chi square and Fisher's exact tests disclosed statistically significant differences between WBS and SPECT/CT scan, concerning cervical lymphadenopathy detection (p=0.031) and relapse prediction by NM stage (p=0.033), respectively; SPECT/CT was more accurate in both comparisons. CONCLUSION: In papillary thyroid carcinoma I-131 post-ablation SPECT/CT scan detects cervical lymphadenopathy and predicts relapse by NM stage more accurately than WBS.

Internal Auditory Canal Tumor as an Incidental Finding on a Choline PET/CT Scan in a Prostate Cancer Patient.

An 84-year-old man with a history of prostate cancer, treated with radiotherapy, presented with an increase in PSA levels. F-choline PET/CT showed foci of increased choline uptake in L4 and L5 vertebrae, suggestive of bone metastases and another focus in the right cerebellopontine angle. A brain MRI revealed a focus of intense contrast enhancement in the same region, consistent with an acoustic neuroma.

Hypermetabolic Calcified Lymph Nodes on 18Fludeoxyglucose-Positron Emission Tomography/Computed Tomography in a Case of Treated Ovarian Cancer Recurrence: Residual Disease or Benign Formation?

The contribution of positron emission tomography/computed tomography (PET/CT) with 18F-fludeoxyglucose (FDG) in evaluating ovarian cancer recurrence even after a prolonged disease-free interval, and in therapy response is well-described. Calcifications observed in CT, although usually attributed to benign conditions, may actually represent active disease. Such an example of calcified formations is psammoma bodies. We present a case of 56-y. o. patient with ovarian cancer relapse at the supraclavicular area 18 years after complete response and disease-free interval. The patient received chemotherapy and underwent 18F-FDG-PET/CT for the evaluation of treatment response. Both CT corrected and uncorrected PET images showed hypermetabolism in the massively calcified lymph nodes in the neck, mediastinum, axilla and abdomen, indicative of active residual disease.

Leydig cell tumour of the ovary localised with positron emission tomography/computed tomography.

Androgen-producing ovarian tumours can lead to assessment difficulties because of their small size. We present a case of virilising steroid cell ovarian tumour in a 41-year-old woman localised with Fluorine-18-Deoxyglucose Positron Emission Tomography/Computed Tomography ((18)FDG-PET/CT). Although the biochemical evaluation pointed to an ovarian source of androgen, diagnostic attempts to localise the source of hyperandrogenism with transvaginal ultrasound (US), and magnetic resonance imaging (MRI) of pelvis failed. Additional evaluation with (18)FDG-PET/CT showed an increased uptake in the right ovary. A laparoscopic right oophorectomy was performed and histopathology examination revealed a 1.2-cm Leydig cell tumour. The patient showed regression of clinical signs.

The impact of FDG-PET/CT on the management of breast cancer patients with elevated tumor markers and negative or equivocal conventional imaging modalities.

OBJECTIVE: To evaluate the clinical impact of fluorodeoxyglucose (FDG)-PET/computed tomography (CT) scan on restaging breast cancer patients with rising tumor markers and negative or equivocal findings in conventional imaging studies. METHODS: We studied 46 patients with breast cancer of an average age of 57.6 years (ranging from 38 to 68 years). All patients were referred for an FDG-PET/CT scan because of elevated tumor markers, without any other obvious clinical or laboratory sign of relapse. Conventional imaging study results were either negative (29 out of 46 patients) or inconclusive (17 out of 46 patients). All patients underwent a whole-body FDG-PET/CT scan in a combined PET/CT. The findings were confirmed by a follow-up at least 9 months later, and when it was possible, final diagnosis was obtained by histopathology. RESULTS: In 34 out of 46 patients, an FDG-PET/CT scan showed sites of increased metabolic activity, indicating active disease. In 23 out of 46 patients, the therapeutic approach and further clinical management were affected. The FDG-PET/CT scan was true-positive in 33 patients, false-positive in one patient, false-negative in five patients, and true-negative in seven patients. On the basis of our results in this population, an FDG-PET/CT scan had a sensitivity of 86.8%, a specificity of 87.5%, and an accuracy of 86.9%. The positive predictive value was 97.1% and the negative predictive value was 58.3%. Clinical management was affected in 50% of these patients. CONCLUSION: The FDG-PET/CT scan plays an important role in restaging breast cancer patients with rising tumor markers and negative or equivocal findings in conventional imaging techniques, with a consequent significant clinical impact on further management in these patients.