Chylous effusions in advanced medullary thyroid cancer patients treated with selpercatinib.

Objective: Selpercatinib is a highly selective RET-inhibitor drug, approved for the treatment of RET-altered lung and thyroid cancers. So far, RET-altered medullary thyroid cancer (MTC) patients treated with selpercatinib showed a remarkable objective response rate and safety profile. However, new treatment emerging adverse events (TEAEs) have been recently reported. The aim of this study was to evaluate the prevalence, features, and clinical management of effusions that are one of these TEAEs. Design: Around 10 of 11 patients with advanced MTC enrolled in the LIBRETTO-201 clinical trial at Endocrinology Unit of the Pisa University Hospital were evaluated for the presence and management of effusions. Methods: We retrospectively evaluated MTC patients treated with selpercatinib. The presence of pleural, pericardial, abdominal, and/or pelvic effusions was evaluated by reviewing the computerized tomography scan performed during the study protocol and up to 24 months of observation. Results: All but one MTC patient experienced previous multikinase inhibitors treatment. Three patients already had effusions before starting selpercatinib treatment. New effusions appeared in eight of ten (80%) patients during the treatment. A chylous nature was documented in patients who underwent fluid aspiration. Whenever a dose reduction was performed, a significant positive effect was observed. Conclusions: Chylous effusions are a new TEAE of selpercatinib treatment. They can appear or worsen at any time during the treatment. For cases with asymptomatic and mild effusions, active surveillance may be appropriate and safe. In symptomatic and/or moderate/severe cases, aspiration of the fluid and a dose reduction can improve this AE, strongly supporting a cause-effect correlation with selpercatinib. Significance statement: Effusions, particularly of chylous nature, represent emergent and quite frequent adverse events in the management of patients affected by advanced MTC on treatment with the highly selective inhibitor selpercatinib. In this study, we evaluated, in a series of MTC patients treated with selpercatinib, the prevalence of pleural, pericardial, abdominal, and/or pelvic effusions. Insights into the diagnosis and treatment of the effusions are provided as well as suggestions for clinical management.

Thigh magnetic resonance imaging for the evaluation of disease activity in patients with idiopathic inflammatory myopathies followed in a single center.

INTRODUCTION: In patients with idiopathic inflammatory myopathies (IIM), magnetic resonance imaging (MRI) has been proposed as a useful tool for diagnosis and follow-up. It may identify muscle inflammation (edema) and fatty infiltration for evaluation of disease activity and damage. Little information is available on the role of MRI in assessment of large cohorts of adult patients with IIM. METHODS: Fifty-one patients underwent MRI of the thigh muscles, laboratory tests, and clinical evaluation, including Physician Global Assessment (PGA) of myositis activity and the Manual Muscle Test 8 (MMT8). RESULTS: Muscle edema correlated significantly with creatine kinase values (P = 0.017) and PGA (P < 0.001). A significant correlation between edema and MMT8 values (P = 0.025) was observed when patients with muscle fatty infiltration were excluded. With respect to clinical diagnosis, the sensitivity of MRI was 92.3%, and specificity was 83.3%. CONCLUSIONS: MRI appears to provide additional information that complements clinical and biochemical examinations. Muscle Nerve 54: 666-672, 2016.

Standardization of MRI and Scintigraphic Scores for Assessing the Severity of Bone Marrow Involvement in Adult Patients With Type 1 Gaucher Disease.

OBJECTIVE: MRI and (99m)Tc-sestamibi scintigraphy are used to estimate bone marrow infiltration in patients with Gaucher disease (GD), but comparison of data obtained at different institutions is difficult because different scores are employed for semiquantitative assessment. We developed normalized scores for comparing data both within a single method (MRI) and between different methods (MRI versus scintigraphy). MATERIALS AND METHODS: We evaluated 51 patients with type 1 GD (26 women, 25 men; mean age ± SD, 36.3 ± 10.9 years old). T1- and T2-weighted turbo spin-echo sequences at 1.5 T served to derive the bone marrow burden score (0-16), the vertebra-disk ratio (VDR), the Terk score (0-3), and the Spanish-MRI score (S-MRI, 0-24). Scintigraphy was scored between 0 and 8. Each score was normalized into four categories: 0 = normal, 1 = mild, 2 = intermediate, 3 = severe involvement. Interobserver and intraobserver agreements were evaluated by kappa statistics; nonparametric statistics with Bonferroni correction assessed correlations among the various original and normalized scores. RESULTS: Interobserver agreement was excellent for the original scores (κ = 0.730-0.843) and even more so for the normalized scores (κ = 0.775-0.940). Intraobserver agreement kappa values ranged from 0.753 to 0.937 for the original scores and 0.851 to 1.000 for the normalized scores. Highly significant correlations were found among the various original scores (r = 0.42-0.86, p values between 0.0296 and < 0.0001), except for VDR versus S-MRI and Terk. Normalization generally induced marginal reductions in statistical significance, whereas S-MRI versus VDR reached statistical significance with the normalized scores. CONCLUSION: Our data indicate no significant loss of statistical information is caused by the normalization we employed. Our approach therefore facilitates comparison of different scores obtained in different institutions with different imaging modalities.

Staging of pelvic lymph nodes in patients with prostate cancer: Usefulness of multiple b value SE-EPI diffusion-weighted imaging on a 3.0 T MR system.

PURPOSE: To evaluate the usefulness of diffusion-weighted imaging (DWI) with a multiple b value SE-EPI sequence on a 3.0 T MR scanner for staging of pelvic lymph nodes in patients with prostate cancer candidate to radical prostatectomy and extended pelvic lymph node dissection (PLND). MATERIALS AND METHODS: Institutional review board approval was obtained and written informed consent was taken from all enrolled subjects. A series of 26 patients with pathologically proven prostate cancer (high or intermediate risk according to D'Amico risk groups) scheduled for radical prostatectomy and PLND underwent 3 T MRI before surgery. DWI was performed using an axial respiratory-triggered spin-echo echo-planar sequence with multiple b values (500, 800, 1000, 1500 s/mm(2)) in all diffusion directions. ADC values were calculated by means of dedicated software fitting the curve obtained from the corresponding ADC for each b value. Fitted ADC measurements were performed at the level of proximal and distal external iliac, internal iliac, and obturator nodal stations bilaterally. Lymph node appearance was also assessed in terms of short axis, long-to-short axis ratio, node contour and intranodal heterogeneity of signal intensity. RESULTS: A total of 173 lymph nodes and 104 nodal stations were evaluated on DWI and pathologically analysed. Mean fitted ADC values were 0.79 ± 0.14 × 10(-3) mm(2)/s for metastatic lymph nodes and 1.13 ± 0.29 × 10(-3) mm(2)/s in non-metastatic ones (P < 0.0001). The cut-off for fitted ADC obtained by ROC curve analysis was 0.91 × 10(-3) mm(2)/s. A two-point-level score was assigned for each qualitative parameter, and the mean grading score was 6.09 ± 0.61 for metastastic lymph nodes and 5.42 ± 0.79 for non-metastatic ones, respectively (P = 0.001). Using a score threshold of 4 for morphological, structural, and dimensional MRI analysis and a cut--off value of 0.91 × 10(-3) mm(2)/s for fitted ADC measurements of pelvic lymph nodes, per--station sensitivity, specificity, PPV, NPV and diagnostic accuracy were 100%, 7.9%, 15.6%, 100% and 21.3%, and 84.6%, 89.5%, 57.9%, 97.1% and 88.8%, respectively. CONCLUSIONS: 3.0T DWI with a multiple b value SE-EPI sequence may help distinguish benign from malignant pelvic lymph nodes in patients with prostate cancer.

[(18)F]Choline PET/CT and stereotactic body radiotherapy on treatment decision making of oligometastatic prostate cancer patients: preliminary results.

BACKGROUND: A new entity of patients with recurrent prostate cancer limited to a small number of active metastatic lesions is having growing interest: the oligometastatic patients. Patients with oligometastatic disease could eventually be managed by treating all the active lesions with local therapy, i.e. either surgery or ablative stereotactic body radiotherapy. This study aims to assess the impact of [(18)F]Choline ([(18)F]FMCH) PET/CT and the use stereotactic body radiotherapy (SBRT) in patients (pts) with oligometastatic prostate cancer (PCa). METHODS: Twenty-nine pts with oligometastatic PCa (≤3 synchronous active lesions detected with [(18)F]FMCHPET/CT) were treated with repeated salvage SBRT until disease progression (development of > three active synchronous metastases). Primary endpoint was systemic therapy-free survival measured from the baseline [(18)F]FMCHPET/CT. RESULTS: A total of 45 lesions were treated with SBRT. After a median follow-up of 11.5 months (range 3-40 months), 20 pts were still in the study and did not receive any systemic therapy. Nine pts started systemic therapy, and the median time of the primary endpoint was 39.7 months (CI 12.20-62.14 months). No grade 3 or 4 toxicity was recorded. CONCLUSIONS: Repeated salvage [(18)F]FMCHPET/CT-guided SBRT is well tolerated and could defer the beginning of systemic therapy in selected patients with oligometastatic PCa.

An unusual case of intrarenal coiled and ruptured guidewire.

OBJECTIVE: To the best of our knowledge there are only 3 reports of fractured guidewires inside the pelvicalyceal system, successfully removed with endourology techniques, and this is the first one presenting a tightly coiled intraparenchymal section. MATERIAL AND METHODS: A 59-year-old woman was hospitalized for surgical treatment of a right kidney of reduced size. Past history revealed pyelolithotomy for a staghorn stone 14 months earlier at another Institution with subsequent ureteral obstruction, one failed attempt at ureteral double-J catheter insertion and one failed attempt at percutaneous nephrostomy placement 5 months postoperatively. Another nephrostomy was placed, but left indwelling briefly. CT scan demonstrated a small-size kidney with residual stone fragments and presence of a "device" in the lower pole. The tapered distal extremity of an hydrophilic guidewire, with a tightly coiled central section wedged in the renal tissue was found inside the nephrectomy specimen. RESULTS: While the Radiologist who read the CT scan hypothesized that the "device" was a fragment of double-J ureteral stent or nephrostomy catheter, it consisted of the hydrophilic extremity of a guidewire, broken during a previous attempt at nephrostomy placement. Perirenal fibrosis and inappropriate angle between the needle and the lower calyx are the likely causes of guidewire coiling during its advancement and subsequent rupture during withdrawal. CONCLUSIONS: Urologists must be aware that, although percutaneous nephrostomy has a very high technical success rate, unusual complications like guidewire fracture may occur, and that modern imaging techniques can provide an accurate picture of this condition.

Time-resolved contrast-enhanced magnetic resonance angiography (CEMRA) of the left atrium-pulmonary veins complex with half dose of intravenous gadolinium-based contrast agent. Technical feasibility and comparison with a conventional CEMRA, full contrast dose protocol.

PURPOSE: To evaluate feasibility and image quality of time-resolved contrast-enhanced magnetic resonance angiography (CEMRA) of the left atrium-pulmonary veins (LA-PV) complex with half dose of intravenous gadolinium-based contrast agent (GBCA) in patients candidate to percutaneous radiofrequency ablation of atrial fibrillation. METHODS AND MATERIALS: Fifty-seven patients underwent CEMRA of the LA-PV complex on a 1.5T MRI scanner. On 24/57 patients, a conventional fast-spoiled gradient-echo (FSPGR) CEMRA acquisition was run using 0.2 mL/kg of 0.5M GBCA at 2 mL/s flow rate (protocol A), while in 33/57 patients a time-resolved multiphase CEMRA sequence (Time-Resolved Imaging of Contrast KineticS, TRICKS) was performed after intravenous injection of 0.1 mL/kg of the same GBCA at 3 mL/s flow rate (protocol B). Contrast enhancement was measured in the LA (LAe) and in the PA (PAe), and the LAe/PAe ratio was calculated. Diagnostic quality of Maximum Intensity Projection (MIP), Volume Rendering (VR), and Virtual Endoscopy (VE) reconstructions was also assessed visually using a semiquantitative score. RESULTS: LAe was comparable with both protocols, while PAe was lower with protocol B than with protocol A (p = 0.0217). Moreover, the LAe/PAe ratio was significantly higher with protocol B than with protocol A (p = 0.0044). Finally, image quality of MIP, VR, and VE reconstructions was significantly better with protocol B than with protocol A (p = 0.0005, p = 0.0001, and p = 0.005, respectively). CONCLUSIONS: CEMRA of the LA-PV complex is feasible with TRICKS and half-dose GBCA and yields better separation between the LA-PV complex and the PA, as well as better image quality of MIP, VR, and VE reconstructions than a conventional FSPGR sequence performed with full GBCA dose.

Role of dynamic MRI in the follow-up of acute Charcot foot in patients with diabetes mellitus.

PURPOSE: To evaluate the usefulness of magnetic resonance imaging (MRI) in assessing the level of activity of acute Charcot foot, monitoring treatment response and predicting healing time. MATERIALS AND METHODS: Forty diabetic patients with acute Charcot foot were prospectively enrolled. Patients underwent limb immobilization and were followed every 3 months by clinical examination (skin temperature and circumferences) and MRI. MR protocol included T1-weighted and fast spin echo inversion recovery (FSE-IR) sequences, and a dynamic study (fast spoiled gradient echo), after gadolinium administration (0.1 ml/kg). The contrast medium uptake rate at D-MRI and the signal intensity (SI) ratio on the FSE-IR sequence were measured. RESULTS: At baseline, mean contrast medium uptake rate was 136 ± 49.7% and the mean SI ratio was 5 ± 3. A high intra- and inter-observer agreement was found for the contrast medium uptake rate, whereas a low agreement was observed for the SI ratio. At 3 months' follow-up, reduction of the contrast medium uptake rate was observed in all patients with improved clinical findings (n = 34), whereas the SI ratio was reduced in 15/34 (44.1%) patients. Mean healing time was significantly related to the baseline contrast medium uptake rate (P=0.005); it was 5.3 ± 2.7 months in patients with contrast medium uptake rate ≤ 100%, compared with 9.1 ± 2.5 months in the remaining patients (P=0.0003). CONCLUSIONS: Contrast medium uptake rate obtained at D-MRI represents a reproducible parameter that is reliable for predicting and monitoring treatment outcome in acute Charcot foot.

Osteoid osteoma in atypical locations: the added value of dynamic gadolinium-enhanced MR imaging.

PURPOSE: To compare the results of dynamic gadolinium-enhanced magnetic resonance imaging (MRI), unenhanced MRI and computed tomography (CT), in terms of nidus conspicuity and diagnostic confidence of osteoid osteoma in atypical sites. MATERIALS AND METHODS: CT and MR (nonenhanced T1- and T2-weighted and dynamic MRI) images of 19 patients with histologically proven osteoid osteoma located in atypical sites were retrospectively reviewed. Time-enhancement curves of the nidus and the adjacent bone marrow were generated. Images from each technique were scored for nidus conspicuity by two independent radiologists. Another blinded radiologist was asked to assess final diagnosis of the bone lesion on MR and CT images, independently. RESULTS: In all cases, nidus contrast uptake started in the arterial phase and was higher compared to the surrounding bone marrow. Dynamic MRI significantly increased nidus conspicuity compared to nonenhanced MRI (P<.0001) and CT (P=.04). In 6/19 (31.6%) cases nidus conspicuity was higher at dynamic MRI compared to CT. Confident diagnosis of osteoid osteoma was achieved in all patients with MRI and in 10/19 (52.6%) patients with CT. CONCLUSION: In patients with osteoid osteoma located in atypical sites, dynamic MRI increases nidus conspicuity, allowing confident diagnosis.

MR evaluation of bone cysts treated with intracavital steroid injection.

The objective of this study was to evaluate the role of MR examination in showing the effects of intralesional steroid injection on bone cysts. Nineteen patients with radiologically suspected (group A, n=15) or already treated (group B, n=4) bone cysts underwent MRI (0.5 T; protocol: T2* gradient recalled echo; short tau inversion recovery or inversion recovery fast spin echo; T1 SE before and after contrast administration, 0.2 mmol/kg). All patients underwent steroid therapy for bone cysts and were followed up for 6-18 months after treatment. Evaluation of bone cyst response to therapy was based mainly on the detection of reparative tissue outlining all cystic portions at first MRI control. In group A, as early as 1 month after the first injection, the presence of a thin reparative tissue lining the cystic wall was observed. Follow-up studies revealed the progressive thickening of this reparative tissue and new bone formation. Similar features were present in the cysts of group B. Residual cystic cavities were depicted in 7 cases, with no evidence of enhancing tissue, requiring further treatment. The formation of a reparative tissue is the first feature of bone cyst recovery after intracavital steroid injection and is appreciable only on MRI. Because of the optimal visualisation of this reparative tissue and of residual cystic cavities, MRI could be proposed as a non-invasive, alternative and effective tool for evaluating the efficacy of steroid injection therapy of bone cysts.

Value of opposed-phase gradient-echo technique in distinguishing between benign and malignant vertebral lesions.

Our objective was to evaluate the possible role of opposed-phase gradient-echo (GRE) sequence in predicting the nature of vertebral lesions supposing that in the case of malignancy fat is completely replaced while in the case of benign lesion fat is still present. Eighty-six patients with vertebral lesions underwent MR examination at 0.5 T. The MR protocol included a T1-weighted spin-echo (SE) and an opposed-phase GRE using the same parameters (TR=280-320 ms, flip angle=90 degrees, slice thickness=3.5-4 mm, matrix=256x160-192, field of view=34-36 cm, no. of excitations=2-4) except for TE (10 ms in SE vs 7 ms in GRE) to obtain opposed-phased images. Qualitative (nature of lesion, detectability, degree of signal intensity (SI), marrow pattern) and quantitative (SI on opposed-phase GRE minus SI on T1-weighted SE minus SI ratio=SI on out-of-phase GRE images divided by SI on T1-weighted SE images) analysis were performed. The SI ratio values were analysed using Mann-Whitney rank-sum test and receiver operating characteristics (ROC) curve. Lesions resulted to be malignant in 45 and benign in 41 patients (23 biopsies, 20 MR follow-ups, 43 clinical and other imaging follow-ups). Based on visual inspection of opposed-phased images, visual SI was evaluated high in 38 (34 malignant, 34 benign), mild in 28 (9 malignant, 19 benign) and low in 20 (2 malignant, 18 benign) patients. Based on region-of-interest measurements, SI ratio values range was 0.36-6.2 (mean value=1.68+/-0.82) for malignant and 0.07-1.54 (mean value=0.77+/-0.44) for benign lesions. A cut-off value of 1.2 gave a sensitivity, specificity, accuracy, negative predictive value and positive predictive value, respectively, of 88.8, 80.49, 84.88, 86.4 and 83.33%. The ROC analysis of the SI ratio showed an area under ROC curve of 0.92 and a statistically significant difference between the two groups of lesions was observed ( p<0.01). The GRE opposed-phase sequence can help to predict the nature of a vertebral lesion. This fast and widely available technique together with morphological criteria can improve the accuracy of MRI.