Contrast-Enhanced Spectral Mammography and tumor size assessment: a valuable tool for appropriate surgical management of breast lesions

Purpose

To compare the accuracy of Contrast-Enhanced Spectral Mammography (CESM), MG, US, and breast MRI in estimating the size of breast lesions requiring surgery. The postoperative histology size of the lesion was used as the gold standard.

Material and methods

Two hundred thirty-three non-benign lesions in 189 patients were included in the analyses. All the selected patients underwent CESM and at least one other conventional diagnostic exam (US, MG, or MRI). Subsequently, all the patients underwent surgery preceded by cytological/histological examination. The largest diameter of the lesion at imaging was measured by a radiologist with more than 10 years’ experience and then compared with the size of the lesion in the histological sample at the surgery (gold standard).

Results

Among the 233 breast lesions, 196 were evaluated with US, 206 with MG and 160 with MRI. We found no statistically significant differences between size measurements using CESM and MRI compared with the measurements at the surgery (p value 0.63 and 0.51), whereas a significant difference was found for MG and US (p?<?0.001).

Conclusion

CESM is a reliable method for estimating the size of breast lesions: its performance seems superior to US and MG and comparable to MRI.

     

Discovery of new inhibitors of Cdc25B dual specificity phosphatases by structure-based virtual screening

Cell division cycle 25 (Cdc25) proteins are highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases and represent attractive drug targets for anticancer therapies. To discover more potent and diverse inhibitors of Cdc25 biological activity, virtual screening was performed by docking 2.1 million compounds into the Cdc25B active site. An initial subset of top-ranked compounds was selected and assayed, and 15 were found to have enzyme inhibition activity at micromolar concentration. Among these, four structurally diverse inhibitors with a different inhibition profile were found to inhibit human MCF-7, PC-3, and K562 cancer cell proliferation and significantly affect the cell cycle progression. A subsequent hierarchical similarity search with the most active reversible Cdc25B inhibitor found led to the identification of an additional set of 19 ligands, three of which were confirmed as Cdc25B inhibitors with IC(50) values of 7.9, 4.2, and 9.9 μM, respectively.     

Two friends with eroded nodules on the ears: atypical fibroxanthoma case report

Atypical fibroxanthoma is an uncommon mesenchymal tumor that manifests clinically as a reddish papule or nodule in sun-exposed areas of the body. The clinical presentation is not specific and histology and immunohistochemistry are both necessary for a correct diagnosis. Surgery is the gold standard of therapy. Recurrence and metastasis should be excluded with a follow-up at 6 months, since this tumor should nowadays be considered a medium-grade neoplasm, rather than low-grade as previously believed. We report the case of two friends who came to our hospital during the same period, complaining of very similar lesions. After biopsy and immunohistochemical examination, a diagnosis of atypical fibroxanthoma in both cases was formulated.     

Discovery of new small molecules inhibiting 67 kDa laminin receptor interaction with laminin and cancer cell invasion

The 67 kDa laminin receptor (67LR) is a non-integrin receptor for laminin (LM) that derives from a 37 kDa precursor (37LRP). 67LR expression is increased in neoplastic cells and correlates with an enhanced invasive and metastatic potential.We used structure-based virtual screening (SB-VS) to search for 67LR inhibitory small molecules, by focusing on a 37LRP sequence, the peptide G, able to specifically bind LM. Forty-six compounds were identified and tested on HEK-293 cells transfected with 37LRP/67LR (LR-293 cells). One compound, NSC47924, selectively inhibited LR-293 cell adhesion to LM with IC₅₀ and K_i values of 19.35 and 2.45 μmol/L.NSC47924 engaged residues W176 and L173 of peptide G, critical for specific LM binding. Indeed, NSC47924 inhibited in vitro binding of recombinant 37LRP to both LM and its YIGSR fragment. NSC47924 also impaired LR-293 cell migration to LM and cell invasion.A subsequent hierarchical similarity search with NSC47924 led to the identification of additional four compounds inhibiting LR-293 cell binding to LM: NSC47923, NSC48478, NSC48861, and NSC48869, with IC₅₀ values of 1.99, 1.76, 3.4, and 4.0 μmol/L, respectively, and able to block in vitro cancer cell invasion.These compounds are promising scaffolds for future drug design and discovery efforts in cancer progression.     

Percutaneous needle biopsy of mediastinal masses under C-arm conebeam CT guidance: diagnostic performance and safety

The aim of this study is to evaluate the feasibility of percutaneous needle biopsy of mediastinal masses under conebeam computed tomography (CBCT) and “XperGuide” navigation guidance. From September 2013 to April 2016, 40 patients (25 men and 15 women; mean age 52.5 years; range 18.7–86.4 years) with 40 mediastinal masses underwent CBCT-/”XperGuide”-guided percutaneous needle biopsies. Technical success, sensibility, specificity, positive predictive value (ppv), negative predictive value (npv) and complications rate were evaluated. Technical success evaluated as the correct positioning of the needle inside the lesion was 100%. Based on histopathological diagnosis, 2 of 40 biopsies (5%) resulted a false negative. Diagnostic accuracy was 95%, sensitivity was 95%, specificity was 100%, ppv was 100%, and npv was 33%. The mean total procedure time was 32 min (range 15–60 min) revealing a reduction in time comparing the first group of 20 patients (mean time 45 min) with the last group of 20 patients (mean time 17 min). No major complications were recorded. Only three patients (7.5%) had mild pneumothorax as demonstrated by post-procedural CBCT, resolved spontaneously. CBCT/“XperGuide” navigation system is a new, safe and accurate technique that can be used as guidance for mediastinal mass biopsies. It also permits the use of CT machines for diagnostic examinations relieving them from interventional procedures burden.     

New concepts in embolotherapy of HCC

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide with rapidly growing incidence rates in the USA and Europe. Despite improving surveillance programs, most patients are diagnosed at intermediate to advanced stages and are no longer amenable to curative therapies, such as ablation, surgical resection and liver transplantation. For such patients, catheter-based image-guided embolotherapies such as transarterial chemoembolization (TACE) represent the standard of care and mainstay therapy, as recommended and endorsed by a variety of national guidelines and staging systems. The main benefit of these therapies is explained by the preferentially arterial blood supply of liver tumors, which allows to deliver the anticancer therapy directly to the tumor-feeding artery while sparing the healthy hepatic tissue mainly supplied by the portal vein. The tool box of an interventional oncologist contains several different variants of transarterial treatment modalities. Ever since the first TACE more than 30 years ago, these techniques have been progressively refined, both with respect to drug delivery materials and with respect to angiographic micro-catheter and image-guidance technology, thus substantially improving therapeutic outcomes of HCC. This review will summarize the fundamental principles, technical and clinical data on the application of different embolotherapies, such as bland transarterial embolization, Lipiodol-based conventional transarterial chemoembolization as well as TACE with drug-eluting beads (DEB-TACE). Clinical data on ⁹⁰Yttrium radioembolization as an emerging alternative, mostly applied for niche indications such as HCC with portal vein invasion, will be discussed. Furthermore, we will summarize the principle of HCC staging, patient allocation and response assessment in the setting of HCC embolotherapy. In addition, we will evaluate the role of cone-beam computed tomography as a novel intra-procedural image-guidance technology. Finally, this review will touch on new technical developments such as radiopaque, imageable DEBs and the rationale and role of combined systemic and locoregional therapies, mostly in combination with Sorafenib.     

Intravoxel Incoherent Motion (IVIM) Diffusion Weighted Imaging (DWI) in the Periferic Prostate Cancer Detection and Stratification

The aim of this study was to compare the Intravoxel Incoherent Motion (IVIM) parameters between healthy Peripheral Zone (PZ), Benign Prostatic Hyperplasia (BPH) and Prostate Cancer (PCa) and compare them to assess whether there was correlation with Gleason Score (GS) grading system. Thirty-one patients with suspect of PCa underwent 1.5T Multi-Parametric Magnetic Resonance Imaging (MP-MRI) with endorectal coil with a protocol including T2WI, DWI using 10 b values (0, 10, 20, 30, 50, 80, 100, 200, 400, 1000 s/mm²) and DCE. Monoexponential and IVIM model fits were used to calculate both apparent diffusion coefficient (ADC) and the following IVIM parameters: molecular diffusion coefficient (D), perfusion-related diffusion coefficient (D*) and perfusion fraction (f). The ADC and D values were significantly lower in the PCa (0.70 ± 0.16 × 10^?3 mm²/s and 0.88 ± 0.31 × 10^?3 mm²/s) compared to those found in the PZ (1.22 ± 0.20 × 10^?3 mm²/s and 1.78 ± 0.34 × 10^?3 mm²/s) and in the BPH (1.53 ± 0.23 × 10^?3 mm²/s and 1.11 ± 0.28 × 10^?3 mm²/s). The D* parameter was significantly increased in the PCa (5.35 ± 5.12 × 10^?3 mm²/s) compare to the healthy PZ (3.02 ± 2.86 × 10^?3 mm²/s), instead there was not significantly difference in the PCa compare to the BPH (5.61 ± 6.77 × 10^?3 mm²/s). The f was statistically lower in the PCa (9.01 ± 5.20%) compared to PZ (10.57 ± 9.30%), but not significantly different between PCa and BPH (9.29 ± 7.29%). The specificity, sensitivity and accuracy of T2WI associated with DWI and IVIM were higher (100, 98 and 99%, respectively) than for T2WI/DWI and IVIM alone (89, 92 and 90%, respectively). Only for ADC was found a statistical difference between low- and intermediate-/high-grade tumors. Adding IVIM to the MP-MRI could increase the diagnostic performance to detect clinically relevant PCa. ADC values have been found to have a rule to discriminate PCa reliably from normal areas and differed significantly in low- and intermediate-/high-grade PCa. In contrast, IVIM parameters were unable to distinguish between the different GS.     

Yttrium-90 radioembolization treatment for unresectable hepatocellular carcinoma: a single-centre prognostic factors analysis

The aim of this study was to evaluate the efficacy and the safety of Y90 radioembolization (Y90-RE) in patients with unresectable hepatocellular carcinoma (HCC) analysing our results and correlating them with independent prognostic factors for overall survival (OS) and for complications. Forty-three patients with advanced inoperable HCC including those with multiple bilobar lesions or portal vein thrombosis (PVT) treated with Y90-RE were reviewed. Treatment efficacy and safety were evaluated. Survival was calculated by the Kaplan–Meier method. Univariate analyses were performed for identifying potential prognostic factors. Radiologic response was evaluated with the modified Response Evaluation Criteria in Solid Tumours (mRECIST) criteria. Clinical toxicities were prospectively recorded. Median overall progression-free survival and OS were 27.7 and 16.8 months, respectively. Longer median OS was revealed in those without PVT (p = 0.0241) and those whose pre-treatment haemoglobin values was higher (p = 0.0471). According with mRECIST criteria, we observed a disease control rate of 69.2 and 61.9% at 3- and 6-month follow-up, respectively. Complications developed in 28 patients (65.1%), among which grade 2–3 events were reported in 17 patients. We noted that activity administered dose presented a correlation with intra-procedural toxicity (p = 0.039259) while common hepatic artery use as release site was associated with a most frequent presentation of remote adverse events. Y90-RE is an alternative treatment with a promising outcome for poor-risk advanced inoperable HCC. PVT and pre-treatment haemoglobin values can be predictors of efficacy. Activity administered dose and arterial release site can be predictors of safety.     

Clinical impact of cone beam computed tomography on iterative treatment planning during ultrasound-guided percutaneous ablation of liver malignancies

A standardized cone beam computed tomography (CBCT) protocol may impact optimal ablation probe(s) positioning during ultrasound-guided microwave ablation (MWA). To evaluate this hypothesis, 15 patients underwent ultrasound-guided percutaneous MWA of 15 liver lesions (10 hepatocellular carcinomas, 5 metastasis ranging 11–41 mm) with the ultrasound guidance assisted by a dedicated CBCT protocol. Pre-procedural enhanced CBCT (ceCBCT) was performed after intravenous contrast administration to visualize the lesion and determine the optimal approach using CBCT-based ablation planning software. MW antennas were positioned under ultrasound guidance, and non-enhanced CBCT was performed after deployment and fused with pre-procedural ceCBCT to assess tumor targeting and modify subsequent steps of the procedure. CBCT lesion detection accuracy and number of needle repositioning on the basis of CBCT information were recorded. Clinical success was measured on 1-month follow-up contrast-enhanced CT. The target lesion was detected on ceCBCT in 13 out of 15 patients (87%). The undetected lesions were only visible on diagnostic contrast-enhanced magnetic resonance imaging, which was then fused to the CBCT and fluoroscopy to facilitate targeting. MW antennas were repositioned on the basis of CBCT in 11 lesions (73%). Clinical success was achieved in 14/15 ablations (93%) with a mean follow-up of X months. The only case of local recurrence was expected, as the intent was tumor debulking. CBCT imaging during ultrasound-guided liver ablation is feasible and leads to ablation device repositioning in the majority of cases.