Good clinical practice recommendations for the use of PET/CT in oncology.

Positron emission tomography/computed tomography (PET/CT) is a nuclear medicine functional imaging technique with proven clinical value in oncology. PET/CT indications are continually evolving with fresh advances made through research. French practice on the use of PET in oncology was framed in recommendations based on Standards-Options-Recommendations methodology and coordinated by the French federation of Comprehensive Cancer Centres (FNLCC). The recommendations were originally issued in 2002 followed by an update in 2003, but since then, a huge number of scientific papers have been published and new tracers have been licenced for market release. The aim of this work is to bring the 2003 version recommendations up to date. For this purpose, a focus group was set up in collaboration with the French Society for Nuclear Medicine (SFMN) to work on developing good clinical practice recommendations. These good clinical practice recommendations have been awarded joint French National Heath Authority (HAS) and French Cancer Institute (INCa) label status-the stamp of methodological approval. The present document is the outcome of comprehensive literature review and rigorous appraisal by a panel of experts, organ specialists, clinical oncologists, surgeons and imaging specialists. These data were also used for the EANM referral guidelines.

Assessment of vertebral microarchitecture in overt and mild Cushing's syndrome using trabecular bone score.

OBJECTIVE: Osteoporotic fractures associated with Cushing's syndrome (CS) may occur despite normal bone mineral density (BMD). Few studies have described alterations in vertebral microarchitecture in glucocorticoid-treated patients and during CS. Trabecular bone score (TBS) estimates trabecular microarchitecture from dual-energy X-ray absorptiometry acquisitions. Our aim was to compare vertebral BMD and TBS in patients with overt CS and mild autonomous cortisol secretion (MACE), and following cure of overt CS. SETTING: University Hospital. DESIGN: Monocentric retrospective cross-sectional and longitudinal studies of consecutive patients. PATIENTS: A total of 110 patients were studied: 53 patients had CS (35, 11 and 7 patients with Cushing's disease, bilateral macronodular adrenal hyperplasia and ectopic ACTH secretion respectively); 39 patients had MACE (10 patients with a late post-operative recurrence of Cushing's disease and 29 patients with adrenal incidentalomas); 18 patients with non-secreting adrenal incidentalomas. 14 patients with overt CS were followed for up to 2 years after cure. RESULTS: Vertebral osteoporosis at BMD and degraded microarchitecture at TBS were found in 24% and 43% of patients with CS, respectively (P < .03). As compared to patients with nonsecreting incidentalomas, patients with MACE had significantly decreased TBS (P < .04) but not BMD. Overt fragility fractures tended to be associated with low TBS (P = .07) but not with low BMD. TBS, but not BMD values, decreased with the intensity of hypercortisolism independently of its aetiology (P < .01). Following remission of CS, TBS improved more markedly and rapidly than BMD (10% vs 3%, respectively; P < .02). CONCLUSION: Trabecular bone score may be a promising, noninvasive, widely available and inexpensive complementary tool for the routine assessment of the impact of CS and MACE on bone in clinical practice.

mTORC1-dependent increase in oxidative metabolism in POMC neurons regulates food intake and action of leptin.

OBJECTIVE: Nutrient availability modulates reactive oxygen species (ROS) production in the hypothalamus. In turn, ROS regulate hypothalamic neuronal activity and feeding behavior. The mechanistic target of rapamycin complex 1 (mTORC1) pathway is an important cellular integrator of the action of nutrients and hormones. Here we tested the hypothesis that modulation of mTORC1 activity, particularly in Proopiomelanocortin (POMC)-expressing neurons, mediates the cellular and behavioral effects of ROS. METHODS: C57BL/6J mice or controls and their knockout (KO) littermates deficient either for the mTORC1 downstream target 70-kDa ribosomal protein S6 kinase 1 (S6K1) or for the mTORC1 component Rptor specifically in POMC neurons (POMC-rptor-KO) were treated with an intracerebroventricular (icv) injection of the ROS hydrogen peroxide (H2O2) or the ROS scavenger honokiol, alone or, respectively, in combination with the mTORC1 inhibitor rapamycin or the mTORC1 activator leptin. Oxidant-related signal in POMC neurons was assessed using dihydroethidium (DHE) fluorescence. RESULTS: Icv administration of H2O2 decreased food intake, while co-administration of rapamycin, whole-body deletion of S6K1, or deletion of rptor in POMC neurons impeded the anorectic action of H2O2. H2O2 also increased oxidant levels in POMC neurons, an effect that hinged on functional mTORC1 in these neurons. Finally, scavenging ROS prevented the hypophagic action of leptin, which in turn required mTORC1 to increase oxidant levels in POMC neurons and to inhibit food intake. CONCLUSIONS: Our results demonstrate that ROS and leptin require mTORC1 pathway activity in POMC neurons to increase oxidant levels in POMC neurons and consequently decrease food intake.

[Hypercalcemia and inactive mutation of CYP24A1. Case-study and literature review]. / Hypercalcémie par mutation inactivatrice du CYP24A1. Étude d'un cas et revue de la littérature.

We present the case of a family whose members have high levels of serum calcium (hypercalcaemia) by loss of function of the enzyme vitamin D 24-hydroxylase due to bi-allelic mutations in the CYP24A1 gene: c.443 T>C (p.Leu148Pro) and c.1187 G>A (p.Arg396Gln). 24-VITD hydroxylase is a key player in regulating the circulating calcitriol, its tissue concentration and its biological effects. Transmission is recessive. The estimated prevalence of stones in the affected subjects is estimated between 10 and 15%. The loss of peripheral catabolism of vitamin D metabolites in patients with an inactivating mutation of CYP24A1 is responsible for persistent high levels of 1,25-dihydroxyvitamin D especially after sun exposure and a charge of native vitamin D. Although there are currently no recommendations (French review) on this subject, this disease should be suspected in association with recurrent calcium stones with nephrocalcinosis, and a calcitriol-dependent hypercalcaemia with adapted low parathyroid hormone levels. Resistance to corticosteroid therapy distinguishes it from other calcitriol-dependent hypercalcemia. A ratio of 25-hydroxyvitamin D/24.25 hydroxyvitamin D>50, is in favor of hypercalcemia with vitamin D deficiency 24-hydroxylase. Genetic analysis of CYP24A1 should be performed at the second step. The current therapeutic management includes the restriction native vitamin D supplementation and the limitation of sun exposure. Biological monitoring will be based on serum calcium control and modulation of parathyroid hormone concentrations.

Pilot study of a 10-week multidisciplinary Tai Chi intervention in sedentary obese women.

OBJECTIVE: Alternative approaches to weight control and physical activity are increasingly needed. Numerous factors influence weight management, including the choice of physical exercise. No study has previously examined the therapeutic effect of a multidisciplinary weight management program incorporating Tai Chi (TC) exercises among sedentary obese women. DESIGN: Randomized intervention trial with blinded medical provider. SETTING: In day hospital consultations. PARTICIPANTS: Twenty-one obese women. INTERVENTION: All subjects participated in a 10-week weight management program that was part of usual care and included a hypocaloric balanced diet, a weekly physician/psychologist/dietician group session, and an exercise program. For the exercise component, subjects were randomized to either a 2-hour weekly session of TC or a conventional structured exercise program. MAIN OUTCOME MEASURES: Changes in weight, body composition, heart rate, blood pressure, mobility scores, mood, Three Factor Eating Questionnaire scores, and General Self-Efficacy. RESULTS: The TC arm improved in resting systolic blood pressure, chair rise test, mood, and reduced percent of fat at week 10 and at 6 months follow-up. General self-efficacy was enhanced in both groups and maintained at 30 weeks. CONCLUSION: The observed benefits over a 30-week period of a multidisciplinary weight management program incorporating TC exercises on physical functioning mood and dietary restraint need further understanding of how sedentary obese women adhere to physical activity like TC or other alternative exercises.

Usefulness of adrenal scintigraphy in the follow-up of adrenocortical incidentalomas: a prospective multicenter study.

OBJECTIVES: Prognostic factors for progression of benign adrenocortical adenomas (AI) remain poorly known. We assessed the usefulness of (131)I-6-beta-iodomethylnorcholesterol scintigraphy (IMS) to predict the occurrence of adrenal hyperfunction or mass enlargement. DESIGN: Fifty-one consecutive inpatients with unilateral AI and normal 24-h urinary free cortisol (UFC) were enrolled in a multicenter observational prospective study to investigate the relationship between the scintigraphic pattern and the progression of biological abnormalities of the hypothalamo-pituitary-adrenal axis or tumor size. RESULTS: Biochemically defined 'subclinical' Cushing's syndrome (SCS) was found at baseline in 47% of patients. Unilateral uptake (UU) was significantly associated with SCS (P<0.05). During the follow-up (4.3+/-1.6-year): 53% of patients showed unchanged hormonal evaluation, 29% displayed intermittent SCS and 18% showed definitive hormonal progression of SCS but without overt biochemical hypercortisolism. UU was associated with persistence of SCS and hormonal progression (P<0.01). In multivariate analysis, UU and impaired 1 mg dexamethasone suppression were independently associated with hormonal progression. Three patients with UU developed clinical CS despite persistently normal UFC. Tumor size increased in 10% patients and was not associated with any scintigraphic pattern. CONCLUSION: Evolution of SCS toward overt biochemical CS in patients with AI is a rare event during a 4-year follow-up. UU is predictive for the occurrence of SCS, its persistence and progression within the spectrum of SCS. Further studies aiming to establish the clinical consequences of SCS are needed to recommend IMS as a complementary evaluation in patients with AI and biochemical SCS.