Central 5-HT neurotransmission modulates weight loss following gastric bypass surgery in obese individuals.

The cerebral serotonin (5-HT) system shows distinct differences in obesity compared with the lean state. Here, it was investigated whether serotonergic neurotransmission in obesity is a stable trait or changes in association with weight loss induced by Roux-in-Y gastric bypass (RYGB) surgery. In vivo cerebral 5-HT2A receptor and 5-HT transporter binding was determined by positron emission tomography in 21 obese [four men; body mass index (BMI), 40.1 ± 4.1 kg/m(2)] and 10 lean (three men; BMI, 24.6 ± 1.5 kg/m(2)) individuals. Fourteen obese individuals were re-examined after RYGB surgery. First, it was confirmed that obese individuals have higher cerebral 5-HT2A receptor binding than lean individuals. Importantly, we found that higher presurgical 5-HT2A receptor binding predicted greater weight loss after RYGB and that the change in 5-HT2A receptor and 5-HT transporter binding correlated with weight loss after RYGB. The changes in the 5-HT neurotransmission before and after RYGB are in accordance with a model wherein the cerebral extracellular 5-HT level modulates the regulation of body weight. Our findings support that the cerebral 5-HT system contributes both to establish the obese condition and to regulate the body weight in response to RYGB.

Reproducibility of (18)F-FDG PET uptake measurements in head and neck squamous cell carcinoma on both PET/CT and PET/MR.

OBJECTIVE: To investigate reproducibility of fluorine-18 fludeoxyglucose ((18)F-FDG) uptake on (18)F-FDG positron emission tomography (PET)/CT and (18)F-FDG PET/MR scans in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: 30 patients with HNSCC were included in this prospective study. The patients were scanned twice before radiotherapy treatment with both PET/CT and PET/MR. Patients were scanned on the same scanners, 3 days apart and according to the same protocol. Metabolic tumour activity was measured by the maximum and peak standardized uptake value (SUVmax and SUVpeak, respectively), and total lesion glycolysis from the metabolic tumour volume defined from ≥50% SUVmax. Bland-Altman analysis with limits of agreement, coefficient of variation (CV) from the two modalities were performed in order to test the reproducibility. Furthermore, CVs from SUVmax and SUVpeak were compared. The area under the curve from cumulative SUV-volume histograms were measured and tested for reproducibility of the distribution of (18)F-FDG uptake. RESULTS: 24 patients had two pre-treatment PET/CT scans and 21 patients had two pre-treatment PET/MR scans available for further analyses. Mean difference for SUVmax, peak and mean was approximately 4% for PET/CT and 3% for PET/MR, with 95% limits of agreement less than ±20%. CV was small (5-7%) for both modalities. There was no significant difference in CVs between PET/CT and PET/MR (p = 0.31). SUVmax was not more reproducible than SUVpeak (p = 0.09). CONCLUSION: (18)F-FDG uptake in PET/CT and PET/MR is highly reproducible and we found no difference in reproducibility between PET/CT and PET/MR. ADVANCES IN KNOWLEDGE: This is the first report to test reproducibility of PET/CT and PET/MR.

Added Diagnostic Value of (11)C-PiB-PET in Memory Clinic Patients with Uncertain Diagnosis.

INTRODUCTION: The added diagnostic value of (11)C-PiB-PET for the assessment of the accumulation of cortical beta-amyloid in memory clinic patients with uncertain diagnosis remains undetermined. METHODS: All patients who underwent PiB-PET at the Copenhagen Memory Clinic between March 2008 and November 2011 were included in this uncontrolled, retrospective study. The standard diagnostic evaluation program included physical and neurological examination, cognitive and functional assessment, a cranial CT or MRI, functional imaging and cerebrospinal fluid sampling. Based on anonymized case reports, three experienced clinicians reached a consensus diagnosis and rated their confidence in the diagnosis before and after disclosure of PiB-PET ratings. PiB-PET scans were rated as either positive or negative. RESULTS: A total of 57 patients (17 females, 30 males; age 65.7 years, range 44.2-82.6) were included in the study. Twenty-seven had a positive PiB-PET scan. At the first diagnostic evaluation, 16 patients were given a clinical Alheimer's disease diagnosis (14 PiB positive). Of the 57 patients, 13 (23%) were diagnostically reclassified after PiB-PET ratings were disclosed. The clinicians' overall confidence in their diagnosis increased in 28 (49%) patients. CONCLUSION: PiB-PET adds to the specialist clinical evaluation and other supplemental diagnostic investigations in the diagnostic classification of patients with uncertain diagnosis in a specialized memory clinic.

Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET).

OBJECTIVES: Atherosclerosis is recognised as an inflammatory disease, and new diagnostic tools are warranted to evaluate plaque inflammatory activity and risk of cardiovascular events. We investigated [18]-fluorodeoxyglucose (FDG) uptake in vulnerable carotid plaques visualised by positron emission tomography (PET). Uptake was correlated to quantitative gene expression of known markers of inflammation and plaque vulnerability. METHODS: Ten patients with recent transient ischaemic attack and carotid artery stenosis (>50%) underwent combined FDG-PET and computed tomography angiography (CTA) the day before carotid endarterectomy. Plaque mRNA expression of the inflammatory cytokine interleukin 18 (IL-18), the macrophage-specific marker CD68 and the two proteinases, Cathepsin K and matrix metalloproteinase 9 (MMP-9), were quantified using real-time quantitative polymerase chain reaction. RESULTS: Consistent up-regulation of CD68 (3.8-fold+/-0.9; mean+/-standard error), Cathepsin K (2.1-fold+/-0.5), MMP-9 (122-fold+/-65) and IL-18 (3.4-fold+/-0.7) were found in the plaques, compared to reference-artery specimens. The FDG uptake by plaques was strongly correlated with CD68 gene expression (r=0.71, P=0.02). Any correlations with Cathepsin K, MMP-9 or IL-18 gene expression were weaker. CONCLUSIONS: FDG-PET uptake in carotid plaques is correlated to gene expression of CD68 and other molecular markers of inflammation and vulnerability.

Guidelines for 18F-FDG PET and PET-CT imaging in paediatric oncology.

OBJECTIVE: The purpose of these guidelines is to offer to the nuclear medicine team a framework that could prove helpful in daily practice. These guidelines contain information related to the indications, acquisition, processing and interpretation of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in paediatric oncology. The Oncology Committee of the European Association of Nuclear Medicine (EANM) has published excellent procedure guidelines on tumour imaging with (18)F-FDG PET (Bombardieri et al., Eur J Nucl Med Mol Imaging 30:BP115-24, 2003). These guidelines, published by the EANM Paediatric Committee, do not intend to compete with the existing guidelines, but rather aim at providing additional information on issues particularly relevant to PET imaging of children with cancer. CONCLUSION: The guidelines summarize the views of the Paediatric Committee of the European Association of Nuclear Medicine. They should be taken in the context of "good practice" of nuclear medicine and of any national rules, which may apply to nuclear medicine examinations. The recommendations of these guidelines cannot be applied to all patients in all practice settings. The guidelines should not be deemed inclusive of all proper procedures or exclusive of other procedures reasonably directed to obtaining the same results.

The effect of spiritual healing on in vitro tumour cell proliferation and viability--an experimental study.

Alternative treatments such as spiritual healing and prayer are increasingly popular, especially among patients with life-threatening diseases such as cancer. According to theories of spiritual healing, this intervention is thought to influence living cells and organisms independently of the recipient's conscious awareness of the healer's intention. The aim of this study was to test the hypothesis that spiritual healing will reduce proliferation and viability of two cancer cell lines in vitro. Three controlled experiments were conducted with three different healers and randomised allocation of cells to five different doses of healing or control. Researchers conducting the assays and statistical analyses were blinded to the experimental conditions. Main outcome measures were MTT viability, 3H-thymidine incorporation and counts of an adherent human breast cancer cell line (MCF-7), and a nonadherent mouse B-lymphoid cell line (HB-94). Analyses of variance (ANOVAs) revealed no significant main or dose-related effects of spiritual healing compared to controls for either of the two cell lines or any of the assays (P-values between 0.09 and 0.96). When comparing healing and control across all three experimental days, doses, assays, and cells, 34 (51.6%) of 66 independent comparisons showed differences in the hypothesised direction (P = 0.90). The average effect size across cell lines, days, assays, and doses approached zero (Cohen's d = -0.01). The results do not support previous reports of beneficial effects of spiritual healing on malignant cell growth in vitro. Reported beneficial effects of spiritual healing on the well-being of cancer patients seem more likely to be mediated by psychosocial and psychophysiological effects of the healer-patient relationship.

PET/CT with intravenous contrast can be used for PET attenuation correction in cancer patients.

PURPOSE: If the CT scan of a combined PET/CT study is performed as a full diagnostic quality CT scan including intravenous (IV) contrast agent, the quality of the joint PET/CT procedure is improved and a separate diagnostic CT scan can be avoided. CT with IV contrast can be used for PET attenuation correction, but this may result in a bias in the attenuation factors. The clinical significance of this bias has not been established. Our aim was to perform a prospective clinical study where each patient had CT performed with and without IV contrast agent to establish whether PET/CT with IV contrast can be used for PET attenuation without reducing the clinical value of the PET scan. METHODS: A uniform phantom study was used to document that the PET acquisition itself is not significantly influenced by the presence of IV contrast medium. Then, 19 patients referred to PET/CT with IV contrast underwent CT scans without, and then with contrast agent, followed by an 18F-fluorodeoxyglucose whole-body PET scan. The CT examinations were performed with identical parameters on a GE Discovery LS scanner. The PET data were reconstructed with attenuation correction based on the two CT data sets. A global comparison of standard uptake value (SUV) was performed, and SUVs in tumour, in non-tumour tissue and in the subclavian vein were calculated. Clinical evaluation of the number and location of lesions on all PET/CT scans was performed twice, blinded and in a different random order, by two independent nuclear medicine specialists. RESULTS: In all patients, the measured global SUV of PET images based on CT with IV contrast agent was higher than the global activity using non-contrast correction. The overall increase in the mean SUV (for two different conversion tables tested) was 4.5+/-2.3% and 1.6+/-0.5%, respectively. In 11/19 patients, focal uptake was identified corresponding to malignant tumours. Eight out of 11 tumours showed an increased SUVmax (2.9+/-3.1%) on the PET images reconstructed using IV contrast. The clinical evaluation performed by the two specialists comparing contrast and non-contrast CT attenuated PET images showed weighted kappa values of 0.92 (doctor A) and 0.82 (doctor B). No contrast-introduced artefacts were found. CONCLUSION: This study demonstrates that CT scans with IV contrast agent can be used for attenuation correction of the PET data in combined modality PET/CT scanning, without changing the clinical diagnostic interpretation.

Positron emission tomography of incidentally detected small pulmonary nodules.

The aim of this study was to assess the value of fluorodeoxyglucose positron emission tomography (FDG PET) imaging of small pulmonary nodules incidentally detected by spiral computed tomography (CT) in a high-risk population. Ten patients (five females, five males, aged 54-72 years) were recruited from an ongoing 4-year placebo controlled intervention study of the effect of inhaled steroids in 300 smokers with moderate to severe chronic obstructive pulmonary disease. The participants received yearly CT scans of the chest. Patients with a negative chest radiograph at the time of inclusion, but with pulmonary nodules indeterminate for malignancy detected by conventional spiral CT on a subsequent scan, were referred for FDG PET. Histological diagnoses were sought for all nodules with FDG uptake or where CT showed that they had grown. Ten patients had pulmonary nodules indeterminate for malignancy (approx. 3.3% of the entire study population). The prevalence of malignancy in this group was 50%. The accuracy of PET was high, in spite of the fact that seven patients had nodules smaller than 15 mm and two patients had bronchoalveolar cell carcinoma. This small prospective study indicates that subsequent assessment with FDG PET of small pulmonary nodules incidentally detected by CT has the potential to minimize the numbers of invasive procedures performed in individuals with a benign pulmonary lesion. FDG PET also increases the possibility of an early diagnosis as compared to the strategy of watchful waiting.

Whole-body FDG-PET in patients with stage I non-seminomatous germ cell tumours.

Relapse occurs in 30% of patients with stage I non-seminomatous germ cell tumours (NSGCT) within 1 year after orchiectomy. Whole-body positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) may detect small metastases when standard staging with computed tomography (CT) and tumour markers is negative. In this study, 46 patients underwent FDG-PET after staging with normal CT and tumour markers. To exclude diagnostic test bias and workup bias, all patients had routine follow-up with repeated CT and tumour marker evaluation, even though the initial FDG-PET was positive. Thirty-six patients have remained disease free with a median follow-up of 48 months (range 24-76). Ten patients (22%) suffered disease relapse after a median of 2 months (range 1-8), and of these, seven had a true positive initial PET with increased uptake of FDG indicating metastatic disease. There were three false negative and no false positive PET scans. The sensitivity, specificity and accuracy of PET were 70%, 100% and 93%, respectively. The sensitivity of detecting small retroperitoneal metastases was 88%. The negative and positive predictive values were 92% and 100%, respectively, whereas the negative predictive value of standard staging procedures was 78%. FDG-PET thus seems to be superior to conventional staging (P=0.06) in stage I NSGCT. This non-invasive method may improve the overall management of patients with NSGCT.

Detection of unknown primary tumours in patients with cerebral metastases using whole-body 18F-flouorodeoxyglucose positron emission tomography.

Identification of the unknown primary tumours in patients presenting with cerebral metastasis is a continued diagnostic challenge. Despite extensive and lengthy diagnostic work-up, the primary tumours will remain obscure in a significant proportion of the patients. The aim of this study was to evaluate the use of whole-body 18-F-fluorodeoxyglucose positron emission tomography (18FDG PET) scanning in this pursuit. Sixteen patients aged 34-74 years, with histologically confirmed metastatic brain tumours, were included in the study. Whole-body 18FDG PET identified pulmonary foci of probable primary tumours in all patients. Subsequent confirmation of tumour tissue was determined either by direct histological verification or indirectly by the observation of lesion appearance or lesion growth on structural imaging. This could only be obtained in eight of 16 patients, all defined as true positive. Of the remaining eight, a biopsy could not be sampled from seven patients, because of death or limited follow-up investigations, and one patient had pulmonary malignant melanoma metastases. Whole-body 18FDG PET scanning is a sensitive tool in the search for unknown primary tumours of patients with confirmed cerebral metastases allowing early and focused histological confirmation from suspicious lesions.

Endoscopic retrograde cholangiopancreatography causes reduced myocardial blood flow.

BACKGROUND AND STUDY AIMS: Previous studies have shown that up to 50% of healthy patients may develop ST-segment changes during upper gastrointestinal endoscopy. The aim of the study was to evaluate myocardial blood flow in patients during endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: 11 patients scheduled for ERCP were monitored with a Holter tape recorder and underwent myocardial perfusion scintigraphies, to evaluate myocardial perfusion at rest and during ERCP. RESULTS: Ten patients completed the study. Eight patients had no sign of myocardial ischemia with either of the two methods, while two patients developed signs of ischemia during ERCP with both the Holter tape recording and on myocardial scintigraphy (P = 0.02). CONCLUSIONS: Patients undergoing ERCP may develop true myocardial ischemia with reduced myocardial blood flow. Although this is a small-scale study, these findings strongly support the use of alternative methods for diagnostic evaluation of the pancreatic duct and biliary tree.

Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy.

OBJECTIVE: Menopause is linked to an increase in fat mass and a decrease in lean mass exceeding age-related changes, possibly related to reduced output of ovarian steroids. In this study we examined the effect of combined postmenopausal hormone replacement therapy (HRT) on the total and regional distribution of fat and lean body mass. RESEARCH METHODS AND PROCEDURES: Sixteen healthy postmenopausal women (age: 55 +/- 3 years) were studied in a placebo-controlled, crossover study and were randomized to 17beta estradiol plus cyclic norethisterone acetate (HRT) or placebo in two 12-week periods separated by a 3-month washout. Total and regional body composition was measured by DXA at baseline and in the 10th treatment week in both periods. Changes were compared by a paired Student's t test. RESULTS: The change in body weight during HRT was equal to the change during placebo (-24.6 g vs. -164 g, p = 0.42), but relative fat mass was significantly reduced (-0.5% vs. +1.24%, p < 0.01). During HRT, compared with during placebo, lean body mass increased (+347 g vs. -996 g, p < 0.01) and total fat mass decreased (-400 g vs. +836 g, p = 0.06). Total bone mineral content increased (+28.9 g vs. -4.4 g, p = 0.04) and abdominal fat decreased (-185 g vs. +253 g, p = 0.04) during HRT compared with placebo. DISCUSSION: HRT is linked to the reversal of both menopause-related obesity and loss of lean mass, without overall change in body weight. The increase in lean body mass during HRT is likely explained by muscle anabolism, which in turn, prevents disease in the elderly.