EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds.

Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Clinical profiles of placenta accreta spectrum: the PACCRETA population-based study.

OBJECTIVE: To describe and compare the characteristics of women with placenta accreta spectrum (PAS) and their pregnancy outcomes according to the presence of placenta praevia and a prior caesarean section. DESIGN: Prospective population-based study. SETTING: All 176 maternity hospitals of eight French regions. POPULATION: Two hundred and forty-nine women with PAS, from a source population of 520 114 deliveries. METHODS: Women with PAS were classified into two risk-profile groups, with or without the high-risk combination of placenta praevia (or an anterior low-lying placenta) and at least one prior caesarean. These two groups were described and compared. MAIN OUTCOME MEASURES: Population-based incidence of PAS, characteristics of women, pregnancies, deliveries and pregnancy outcomes. RESULTS: The PAS population-based incidence was 4.8/10 000 (95% CI 4.2-5.4/10 000). After exclusion of women lost to follow up from the analysis, the group with placenta praevia and a prior caesarean included 115 (48%) women and the group without this combination included 127 (52%). In the group with both factors, PAS was more often suspected antenatally (77% versus 17%; P < 0.001) and more often percreta (38% versus 5%; P < 0.001). This group also had more hysterectomies (53% versus 21%, P < 0.001) and higher rates of blood product transfusions, maternal complications, preterm births and neonatal intensive care unit admissions. Sensitivity analysis showed similar results after exclusion of women who delivered vaginally. CONCLUSION: More than half the cases of PAS occurred in women without the combination of placenta praevia and a prior caesarean delivery, and these women had better maternal and neonatal outcomes. We cannot completely rule out that some of the women who delivered vaginally had placental retention rather than PAS; however, we found similar results among women who delivered by caesarean. TWEETABLE ABSTRACT: Half the women with PAS do not have both placenta praevia and a prior caesarean delivery, and they have better maternal outcomes.

Radioembolization of hepatocarcinoma with 90Y glass microspheres: treatment optimization using the dose-toxicity relationship.

AIM: Transarterial radioembolization (TARE) is, by all standards, a radiation therapy. As such, according to Euratom Directive 2013/59, it should be optimized by a thorough treatment plan based on the distinct evaluation of absorbed dose to the lesions and to the non-tumoural liver (two-compartment dosimetry). Since the dosimetric prediction with 99mTc albumin macro-aggregates (MAA) of non-tumoural liver is much more accurate than the same prediction on lesions, treatment planning should focus on non-tumoural liver rather than on lesion dosimetry. The aim of this study was to determine a safety limit through the analysis of pre-treatment dosimetry with 99mTc-MAA single photon emission computed tomography (SPECT/CT), in order to deliver the maximum tolerable absorbed dose to non-tumoural liver. METHODS: Data from intermediate/advanced hepato-cellular carcinoma (HCC) patients treated with 90Y glass microspheres were collected in this single-arm retrospective study. Injection was always lobar, even in case of bilobar disease, to avoid treating the whole liver in a single session. A three-level definition of liver decompensation (LD) was introduced, considering toxicity only in cases of liver decompensation requiring medical action (LD type C, LDC). We report LDC rates, receiver operating characteristic (ROC) analysis between LDC and NO LDC absorbed dose distributions, normal tissue complication probability (NTCP) curves and uni- and multivariate analysis of risk factors associated with toxicity. RESULTS: A 6-month timeline was defined as necessary to capture all treatment-related toxicity events. Previous transarterial chemoembolization (TACE), presence or extension of portal vein tumoural thrombosis (PVTT) and tumour pattern (nodular versus infiltrative) were not associated with tolerance to TARE. On the contrary, at the multivariate analysis, the absorbed dose averaged over the whole non-tumoural liver (including the non-injected lobe) was a prognostic indicator correlated with liver decompensation (odds ratio = 4.24). Basal bilirubin > 1.1 mg/dL was a second even more significant risk factor (odds ratio = 6.35). NTCP analysis stratified with this bilirubin cut-off determined a 15% liver decompensation risk at 50 Gy/90 Gy for bilirubin >/< 1.1 mg/dL. These results are valid for a 90Y glass microsphere administration 4 days after the reference time. CONCLUSION: Given the low predictive accuracy of 99mTc-MAA on lesion absorbed dose reported by several authors, an optimized TARE with 90Y glass microspheres with lobar injection 4 days after reference time should aim at an absorbed dose averaged over the whole non-tumoural liver of 50 Gy/90 Gy for basal bilirubin higher/lower than 1.1 mg/dL, respectively.

High uric acid, reduced glomerular filtration rate and non-alcoholic fatty liver in young people with obesity.

OBJECTIVE: To evaluate the association between high uric acid (UA), reduced estimated glomerular filtration rate (eGFR), and non-alcoholic fatty liver disease (NAFLD) in outpatient children and adolescents with overweight (OW) or obesity (OB). METHODS: Anthropometric, biochemical, hepatic ultrasound and eGFR data were available from 2565 young people with OW/OB (age 5-18 years). eGFR was calculated using the Schwartz's bedside formula and reduced eGFR (ReGFR+) was defined by a value < 90 mL/min/1.73 m2. High UA was defined as ≥ 75th percentile by sex in children and adolescents. RESULTS: The population was stratified in four categories: (1) normal eGFR and absence of NAFLD (ReGFR-/NAFLD-) (n = 1,236); (2) ReGFR+ and absence of NAFLD (ReGFR+/NAFLD- (n = 155); (3) normal eGFR and presence of NAFLD (ReGFR-/NAFLD+) (n = 1019); (4) presence of both conditions (ReGFR+/NAFLD+) (n = 155). Proportions of youth with high UA across the four categories were 17%, 30%, 33% and 46%, respectively (P < 0.0001). Young people with high levels of UA had odds ratio (95% CI) of 2.11 (1.43-3.11) for ReGFR+; 2.82 (2.26-3.45) for NAFLD+; and 5.04 (3.45-7.39) for both conditions (P < 0.0001 for all), independently of major confounders. CONCLUSIONS: High levels of UA were independently associated with ReGFR, NAFLD and the combination of both conditions in young people with OW/OB. The strength of this association was the highest in cases presenting both reduced eGFR and NAFLD. UA may serve as marker to identify patients at risk for these conditions.

Preclinical signs of liver and cardiac damage in youth with metabolically healthy obese phenotype.

BACKGROUND AND AIMS: We aimed to evaluate whether the metabolically healthy obese (MHO) phenotype was associated with hepatic steatosis (HS) or left ventricular hypertrophy (LVH) in young people with overweight (OW), obesity (OB) and morbid obesity (MOB) and whether the prevalence of these comorbidities was affected by OB severity. METHODS AND RESULTS: An abdominal ultrasound was performed in 1769 children and adolescents, mean age 10.6 years (range 5-18) with MHO phenotype, defined as the absence of traditional cardiometabolic risk factors, in order to identify HS. In a subsample of 177 youth the presence of LVH, defined by 95th percentile of LV mass/h2.7 for age and gender, was also analyzed. The prevalence of HS increased from 23.0% in OW to 27.8% in OB and 45.1% in MOB (P < 0.0001). The proportion of LVH increased from 36.8% in OW to 57.9% in OB and 54.5% in MOB (P < 0.05). As compared with OW, the odds ratio (95% CI) for HS was 2.18 (1.56-3.05), P < 0.0001) in OB and 6.20 (4.26-9.03), P < 0.0001) in MOB, independently of confounding factors. The odds ratio for LVH was 2.46 (1.20-5.06), P < 0.025) in OB and 2.79 (1.18-6.61), P < 0.025) in MOB, as compared with OW. CONCLUSION: In spite of the absence of traditional cardiometabolic risk factors, the prevalence of HS and LVH progressively increased across BMI categories. MHO phenotype does not represent a "benign" condition in youth.

Does endogenous GLP-1 affect resting energy expenditure and fuel selection in overweight and obese adults?

PURPOSE: To investigate the association between fasting glucagon-like peptide 1 (GLP-1) levels and resting energy expenditure (REE), and respiratory quotient (RQ) in overweight and obese adults. METHOD: Study participants were enrolled at the Dietetic and Metabolic Unit, University of Pavia, Italy. Inclusion criteria were age ≥ 25 and ≤ 45 years, and body mass index (BMI) ≥ 25 and ≤ 35 kg/m2. Diabetic subjects were excluded. Body composition was measured by dual-energy X-ray absorptiometry. REE was evaluated using indirect calorimetry, and RQ was calculated from respiratory gas exchanges. Fasting GLP-1, glucose, insulin and free fatty acid (FFA) levels, and 24-h norepinephrine urinary excretion were measured. Homeostasis model assessments of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß) were calculated. RESULTS: Thirty-seven participants were included (age 43.4 ± 1.6 years; BMI 30.6 ± 0.5 kg/m2). REE was not associated with fasting GLP-1 levels (p = 0.98) after adjustment for age, sex, fat-free mass (FFM), and fat mass (FM). Similarly, no association was observed between RQ and GLP-1 levels (p = 0.95), after adjustment for age, sex, and body fat. CONCLUSION: In adults subjects with increased adiposity fasting, GLP-1 levels do not seem to play a role in the regulation of energy metabolism and in fuel selection.

A new index to simplify the screening of hypertension in overweight or obese youth.

BACKGROUND AND AIMS: Hypertension (HTH) is a frequent complication in pediatric obesity. To simplify the screening of HTH in overweight/obese (Ow/Ob) youth, we compared the performance of a new index (High Blood Pressure index, HBPi) with respect to the standard criteria of the IV Report [systolic BP (SBP) and/or diastolic BP (DBP) ≥95th percentile for age, gender and height]. We also compared the performance of HBPi with other simplified indices such as the BP/height ratio and the absolute height-specific BP thresholds. Ten pediatrics' outpatient centers participating in the "CARdiometabolic risk factors in ITALY study" provided medical records of 4225 Ow/Ob children and adolescents (age 6-16 years). METHODS AND RESULTS: Centers were divided into two groups: training set (TS) (n = 2204 participants) and validation set (VS) (n = 2021 participants). The simplified HBPi (mmHg) was: (SBP/2 + DBP/10) - age + (1 × female gender). In the TS, a HBPi value ≥57 mmHg in both children and adolescents had high sensitivity (0.89), specificity (0.97), positive (0.89) and negative (0.97) predictive values in classifying youth at high risk of HTN compared with the IV Report. In the VS, the HBPi showed a better performance than high levels of BP/height ratio and height-specific BP thresholds in classifying individuals at risk of HTN: area under curves 0.95 (0.93-0.96), 0.80 (0.78-0.82), 0.76 (0.74-0.79), respectively; specificities 0.95 (0.94-0.96), 0.69 (0.67-0.72), 0.60 (0.57-0.62), respectively. CONCLUSIONS: HBPi, combining SBP and DBP, gender and age, may help pediatricians to implement HTN screening in Ow/Ob youth.

Impaired fasting glucose and impaired glucose tolerance in children and adolescents with overweight/obesity.

OBJECTIVE: To investigate in a large sample of overweight/obese (OW/OB) children and adolescents the prevalence of prediabetic phenotypes such as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and to assess their association with cardiometabolic risk (CMR) factors including hepatic steatosis (HS). METHODS: Population data were obtained from the CARdiometabolic risk factors in children and adolescents in ITALY study. Between 2003 and 2013, 3088 youths (972 children and 2116 adolescents) received oral glucose tolerance test (OGTT) and were included in the study. In 798 individuals, abdominal ultrasound for identification of HS was available. RESULTS: The prevalence of IFG (3.2 vs. 3.3%) and IGT (4.6 vs. 5.0%) was similar between children and adolescents. Children with isolated IGT had a 2-11 fold increased risk of high LDL-C, non-HDL-C, Tg/HDL-C ratio, and low insulin sensitivity, when compared to those with normal glucose tolerance (NGT). No significant association of IFG with any CMR factor was found in children. Among adolescents, IGT subjects, and to a lesser extent those with IFG, showed a worse CMR profile compared to NGT subgroup. In the overall sample, IGT phenotype showed a twofold increased risk of HS compared to NGT subgroup. CONCLUSIONS: Our study shows an unexpected similar prevalence of IFG and IGT between children and adolescents with overweight/obesity. The IGT phenotype was associated with a worse CMR profile in both children and adolescents. Phenotyping prediabetes conditions by OGTT should be done as part of prediction and prevention of cardiometabolic diseases in OW/OB youth since early childhood.

White blood cell count may identify abnormal cardiometabolic phenotype and preclinical organ damage in overweight/obese children.

BACKGROUND AND AIMS: Subclinical inflammation is a central component of cardiometabolic disease risk in obese subjects. The aim of the study was to evaluate whether the white blood cell count (WBCc) may help to identify an abnormal cardiometabolic phenotype in overweight (Ow) or obese (Ob) children. METHODS AND RESULTS: A cross-sectional sample of 2835 Ow/Ob children and adolescents (age 6-18 years) was recruited from 10 Italian centers for the care of obesity. Anthropometric and biochemical variables were assessed in the overall sample. Waist to height ratio (WhtR), alanine aminotransferase (ALT), lipids, 2 h post-load plasma glucose (2hPG), left ventricular (LV) geometry and carotid intima-media thickness (cIMT) were assessed in 2128, 2300, 1834, 535 and 315 children, respectively. Insulin resistance and whole body insulin sensitivity index (WBISI) were analyzed using homeostatic model assessment (HOMA-IR) and Matsuda's test. Groups divided in quartiles of WBCc significantly differed for body mass index, WhtR, 2hPG, HOMA-IR, WBISI, lipids, ALT, cIMT, LV mass and relative wall thickness. Children with high WBCc (≥8700 cell/mm(3)) showed a 1.3-2.5 fold increased probability of having high normal 2hPG, high ALT, high cIMT, or LV remodeling/concentric LV hypertrophy, after adjustment for age, gender, pubertal status, BMI and centers. CONCLUSIONS: This study shows that WBCc is associated with early derangements of glucose metabolism and preclinical signs of liver, vascular and cardiac damage. The WBCc may be an effective and low-cost tool for identifying Ow and Ob children at the greatest risk of potential complications.

Radioembolization of hepatocarcinoma with (90)Y glass microspheres: development of an individualized treatment planning strategy based on dosimetry and radiobiology.

PURPOSE: The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for an individualized treatment planning strategy based on (99m)Tc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images. METHODS: We performed retrospective dosimetry of the standard TheraSphere® treatment on 52 intermediate (n = 17) and advanced (i.e. portal vein thrombosis, n = 35) hepatocarcinoma patients with tumour burden < 50% and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on (99m)Tc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of (99m)Tc-MAA and (90)Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS™ by Philips). STRATOS™ absorbed dose calculation was validated for (90)Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BEDave) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were derived. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve was used as a figure of merit to identify the methodology which gave the best separation in terms of dosimetry between responding and non-responding lesions and liver decompensated vs non-decompensated liver treatment. RESULTS: MAA and (90)Y biodistributions were not different (71% of cases), different in 23% and uncertain in 6%. Response correlated with absorbed dose (Spearman's r from 0.48 to 0.69). Responding vs non-responding lesion absorbed doses were well separated, regardless of the methodology adopted (p = 0.0001, AUC from 0.75 to 0.87). EUBED gave significantly better separation with respect to mean dose (AUC = 0.87 vs 0.80, z = 2.07). Segmentation on SPECT gave better separation than on SPECT/CT. TCP(50%) was at 250 Gy for small lesion volumes (<10 cc) and higher than 1,000 Gy for large lesions (>10 cc). Apparent radiosensitivity values from TCP were around 0.003/Gy, a factor of 3-5 lower than in EBRT, as found by other authors. The dose-rate effect was negligible: a purely linear model can be applied. Toxicity incidence was significantly larger for Child B7 patients (89 vs 14%, p < 0.0001), who were therefore excluded from dose-toxicity analysis. Child A toxic vs non-toxic treatments were significantly separated in terms of dose averaged on whole non-tumoural parenchyma (including non-irradiated regions) with AUC from 0.73 to 0.94. TD50 was ≈ 100 Gy. No methodology was superior to parenchyma mean dose, which therefore can be used for planning, with a limit of TD15 ≈ 75 Gy. CONCLUSION: A dosimetric treatment planning criterion for Child A patients without complete obstruction of the portal vein was developed.

A double-blind, placebo-controlled randomized trial to evaluate the efficacy of docosahexaenoic acid supplementation on hepatic fat and associated cardiovascular risk factors in overweight children with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Very little information is available on whether docosahexaenoic acid (DHA) supplementation has a beneficial effect on liver fat and cardiovascular disease (CVD) risk factors in children with nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled randomized trial we investigated whether 6-month treatment with DHA improves hepatic fat and other fat depots, and their associated CVD risk factors in children with biopsy-proven NAFLD. METHODS AND RESULTS: Of 58 randomized children, 51 (25 DHA, 26 placebo) completed the study. The main outcome was the change in hepatic fat fraction as estimated by magnetic resonance imaging. Secondary outcomes were changes in visceral adipose tissue (VAT), epicardial adipose tissue (EAT), and left ventricular (LV) function, as well as alanine aminotransferase (ALT), triglycerides, body mass index-standard deviation score (BMI-SDS), and insulin sensitivity. At 6 months, the liver fat was reduced by 53.4% (95% CI, 33.4-73.4) in the DHA group, as compared with 22.6% (6.2-39.0) in the placebo group (P = 0.040 for the comparison between the two groups). Likewise, in the DHA group VAT and EAT were reduced by 7.8% (0-18.3) and 14.2% (0-28.2%), as compared with 2.2% (0-8.1) and 1.7% (0-6.8%) in the placebo group, respectively (P = 0.01 for both comparisons). There were no significant between-group changes for LV function as well as BMI-SDS and ALT, while fasting insulin and triglycerides significantly decreased in the DHA-treated children (P = 0.028 and P = 0.041, respectively). CONCLUSIONS: DHA supplementation decreases liver and visceral fat, and ameliorates metabolic abnormalities in children with NAFLD.

Diagnostic accuracy and interobserver agreement of Quasistatic Ultrasound Elastography in the diagnosis of thyroid nodules.

PURPOSE: To assess the best technique and the diagnostic accuracy of Quasistatic Ultrasound Elastography (QUE) in thyroid nodules. Interobserver agreement was also evaluated. MATERIALS AND METHODS: A preliminary study of 50 patients with 54 thyroid nodules was performed with quantitative software in order to define the best cut-off value of different imaging methods. All patients underwent total thyroidectomy and histopathology findings served as the standard of reference. Thereafter, 154 nodules in 137 consecutive patients were prospectively evaluated by three operators. Findings at fine-needle aspiration cytology and histopathology (N = 60) served as the standard of reference. RESULTS: The most accurate technique was the axial peri-intranodular measurement method which achieved an area under the ROC curve of 0.961 (95 %CI 0.848 - 1.00) and had an optimal cut-off value of 3.00. QUE in the differentiation of thyroid nodules showed for operator 1: sensitivity 90 % (95 %CI 73.5 - 97.9 %), specificity 92.7 % (95 %CI 86.7 - 96.6 %), LR+ 12.40 (6.54 - 23.50), LR- 0.11 (0.04 - 0.32) and accuracy 91.4 % (95 %CI 85.4 - 97.3 %); for operator 2: sensitivity 86.7 % (95 %CI 69.3 - 96.2 %), specificity 87.1 % (95 %CI 79.9 - 92.4 %), LR+ 6.72 (4.16 - 10.80), LR- 0.15 (0.06 - 0.38) and accuracy 86.9 % (95 %CI 80.0 - 93.7 %); for operator 3: sensitivity 80 % (95 %CI 61.4 - 92.3 %), specificity 83.9 % (95 %CI 76.2 - 89.9 %), LR+ 4.96 (3.20 - 7.70), LR- 0.24 (0.12 - 0.49) and accuracy 81.9 % (95 %CI 74.0 - 89.9 %). Interobserver agreement values between operator 1 and operator 2 (k = 0.79) (p < 0.05, 95 %CI 0.684 - 0.904), between operator 1 and operator 3 (k = 0.73, 95 %CI: 0.607 - 0.854) and between operator 2 and operator 3 (k = 0.71, 95 %CI: 0.584 - 0.835) were significant. CONCLUSION: QUE provides accurate quantitative evaluation of thyroid nodules with low interobserver variability.

Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [(90)Y]DOTA-TATE and [(177)Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter ((90)Y) and a medium-energy beta/gamma emitter ([(177)Lu) in patients with metastatic NET refractory to conventional therapy. METHODS: A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [[(177)Lu]DOTA-TATE (5.55 GBq) and [(90)Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [[(177)Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. RESULTS: Administration of tandem [(90)Y]DOTA-TATE and [[(177)Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment. CONCLUSION: The results of our study indicates that combined [(90)Y]DOTA-TATE and [(177)Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach.

Association of serum triglyceride-to-HDL cholesterol ratio with carotid artery intima-media thickness, insulin resistance and nonalcoholic fatty liver disease in children and adolescents.

BACKGROUND AND AIMS: The triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C) ratio has been reported as a useful marker of atherogenic lipid abnormalities, insulin resistance, and cardiovascular disease. We evaluated in a large sample of children and adolescents the association of TG/HDL-C ratio with early signs of morphological vascular changes and cardiometabolic risk factors including nonalcoholic fatty liver disease (NAFLD). METHODS AND RESULTS: The study population, including 548 children (aged 6-16 years), of whom 157 were normal-weight, 118 overweight, and 273 obese, had anthropometric, laboratory, liver and carotid ultrasonography (carotid artery intima-media thickness-cIMT) data collected. Subjects were stratified into tertiles of TG/HDL-C. There was a progressive increase in body mass index (BMI), BMI-SD score (SDS), waist circumference, blood pressure (BP), liver enzymes, glucose, insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein (hsCRP), and cIMT values across TG/HDL-C tertiles. The odds ratios for central obesity, insulin resistance, high hsCRP, NAFLD, metabolic syndrome, and elevated cIMT increased significantly with the increasing tertile of TG/HDL-C ratio, after adjustment for age, gender, pubertal status, and BMI-SDS. In a stepwise multivariate logistic regression analysis, increased cIMT was associated with high TG/HDL-C ratio [OR, 1.81 (95% CI, 1.08-3.04); P < 0.05], elevated BP [5.13 (95% CI, 1.03-15.08); P < 0.05], insulin resistance [2.16 (95% CI, 1.30-3.39); P < 0.01], and NAFLD [2.70 (95% CI, 1.62-4.56); P < 0.01]. CONCLUSION: TG/HDL-C ratio may help identify children and adolescents at high risk for structural vascular changes and metabolic derangement.

Arterial function and structure after a 1-year lifestyle intervention in children with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Lifestyle modification has been the mainstay of controlling childhood obesity and has proved to be effective in reducing cardiovascular risk factors. However, it is currently unknown whether the subclinical atherosclerotic changes associated with nonalcoholic fatty liver disease (NAFLD) in such population are reversible. METHODS AND RESULTS: We analyzed changes of brachial flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), clinical, laboratory, and imaging data in 120 obese children with NAFLD, at the end of a 1-year intervention program with diet and physical exercise. The lifestyle intervention led to a significant mean decrease of body mass index (BMI)-standard deviation score (SDS), waist circumference (WC) and fat mass, along with diastolic blood pressure, triglycerides, liver enzymes, insulin, insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and high-sensitivity C-reactive protein. At the end of the study, FMD improved (P < 0.0001), while cIMT did not change significantly (P = 0.20). A significant decrease in hepatic fat content as measured by magnetic resonance imaging was also observed. Changes in FMD were inversely associated with changes in BMI-SDS, WC, total cholesterol, non-HDL cholesterol, liver enzymes, HOMA-IR, physical activity, and hepatic fat content. After including in the model all the significant variables as well as age, gender, pubertal status, and baseline FMD values, changes in FMD were significantly and independently associated with changes in WC and total cholesterol. CONCLUSION: Also in obese children with NAFLD arterial function may be restored by improving metabolic risk factors and reducing visceral adiposity following a 1-year lifestyle intervention.

An unusual subcutaneous breast cancer metastasis in a 86-year-old woman.

The most common metastasis site of breast cancer are the local and distant lymph nodes, bone, lungs, liver and brain. We report a 86-year-old woman with an unusual abdominal subcutaneous metastasis of breast cancer. The patient was diagnosed with invasive lobular breast cancer and had been treated six months earlier with modified radical mastectomy. Later she presented a painless mass on the middle upper abdominal wall. She was subsequently admitted to the hospital to perform a whole body CT scan, confirming the presence of the abdominal mass in epigastric region, causing a partial compression of the stomach. Histopathological studies confirmed that the abdominal mass was a rare subcutaneous metastatic lesion of breast origin. The patient underwent a surgical intervention to remove the metastasis and she recovered fully.

A novel approach to study oxidative stress in thyroid diseases: a preliminary study.

BACKGROUND AND OBJECTIVES: Recently, several Authors have emphasized the relationship between oxidative stress and thyroid tumors. Several methods have been proposed in the literature for the measurement of oxidative stress in human tissues, although the high reactivity and short half life of reactive oxygen and nitrogen species make difficult their direct determination. Here we propose a novel approach for the determination of oxidative stress in human tissues, taking into account the relationship between free radicals and thyroid diseases. MATERIALS AND METHODS: Our goal in this preliminary study, was to demonstrate the opportunity to use the coupling of the EPR-spin trapping technique with the hydroxylamine 1-hydroxy-3-carboxy-pyrrolidine, to detect oxidative stress in the human blood of patients with thyroid disease. RESULTS: Our preliminary findings confirm that this is a sensible, precise and valid method to study the oxidative stress and encourage us to continue the project. CONCLUSIONS: Our next goal will be to enroll patients affected by different thyroid diseases and to study the effect of some antioxidants in the management of the disease. This will allow to better understand the pathological path that binds the formation of reactive oxidizing species to the thyroid cancer and eventually to take into account the antioxidant therapy, as a possible additional "therapeutic weapon".