Growth of Focal Nodular Hyperplasia is Not a Reason for Surgical Intervention, but Patients Should be Referred to a Tertiary Referral Centre.

BACKGROUND: When a liver lesion diagnosed as focal nodular hyperplasia (FNH) increases in size, it may cause doubt about the initial diagnosis. In many cases, additional investigations will follow to exclude hepatocellular adenoma or malignancy. This retrospective cohort study addresses the implications of growth of FNH for clinical management. METHODS: We included patients diagnosed with FNH based on ≥2 imaging modalities between 2002 and 2015. Characteristics of patients with growing FNH with sequential imaging in a 6-month interval were compared to non-growing FNH. RESULTS: Growth was reported in 19/162 (12%) patients, ranging from 21 to 200%. Resection was performed in 4/19 growing FNHs; histological examination confirmed FNH in all patients. In all 15 conservatively treated patients, additional imaging confirmed FNH diagnosis. No adverse outcomes were reported. No differences were found in characteristics and presentation of patients with growing or non-growing FNH. CONCLUSION: This study confirms that FNH may grow significantly without causing symptoms. A significant increase in size should not have any implications on clinical management if confident diagnosis by imaging has been established by a tertiary benign liver multidisciplinary team. Liver biopsy is only indicated in case of doubt after state-of-the-art imaging. Resection is deemed unnecessary if the diagnosis is confirmed by multiple imaging modalities in a tertiary referral centre.

Cardiovascular, renal and gastrointestinal effects of incretin-based therapies: an acute and 12-week randomised, double-blind, placebo-controlled, mechanistic intervention trial in type 2 diabetes.

INTRODUCTION: Incretin-based therapies, that is, glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in type 2 diabetes management. Apart from glucose-lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, heart failure, acute renal failure and acute pancreatitis. Conversely, these agents may reduce blood pressure, glomerular hyperfiltration, albuminuria and hepatic steatosis. While large-sized cardiovascular safety trials can potentially identify the clinical significance of some of these pleiotropic actions, small-sized mechanistic studies are important to understand the (patho)physiological rationale of these findings. The current protocol describes a mechanistic study to assess cardiovascular, renal and gastrointestinal effects, and mechanisms of incretin-based therapies in type 2 diabetes. METHODS AND ANALYSES: 60 patients with type 2 diabetes will undergo acute and prolonged randomised, double-blind, intervention studies. The acute intervention will consist of intravenous administration of the GLP-1 receptor agonist exenatide or placebo. For the prolonged intervention, patients will be randomised to 12-week treatment with the GLP-1 receptor agonist liraglutide, the DPP-4 inhibitor sitagliptin or matching placebos. For each examined organ system, a primary end point is defined. Primary cardiovascular end point is change in resting heart rate variability assessed by beat-to-beat heart rate monitor and spectral analyses software. Primary renal end point is change in glomerular filtration rate assessed by the classic inulin clearance methodology. Primary gastrointestinal end points are change in pancreatic exocrine function assessed by MRI-techniques (acute intervention) and faecal elastase-1 levels (12-week intervention). Secondary end points include systemic haemodynamics, microvascular function, effective renal plasma flow, renal tubular function, pancreatic volume and gallbladder emptying-rate. MEDICAL ETHICS AND DISSEMINATION: The study is approved by the local Ethics Review Board (VU University Medical Center, Amsterdam) and conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. TRIAL REGISTRATION NUMBER: NCT01744236.

A Clinical and Experimental Comparison of Time of Flight PET/MRI and PET/CT Systems.

PURPOSE: The purpose of the study was to compare image quality and quantitative accuracy of positron emission tomography/magnetic resonance imaging (PET/MRI) and PET/computed tomography (PET/CT) systems with time of flight PET gantries, using phantom and clinical studies. PROCEDURES: Identical phantom experiments were performed on both systems. Calibration, uniformity, and standardized uptake value (SUV) recovery were measured. A clinical PET/CT versus PET/MRI comparison was performed using [(18)F]fluoromethylcholine ([(18)F]FCH). RESULTS: Calibration accuracy and image uniformity were comparable between systems. SUV recovery met EANM/EARL requirements on both scanners. Thirty-four lesions with comparable PET image quality were identified. Lesional SUVmax differences of 4 ± 26% between PET/MRI and PET/CT data were observed (R (2) = 0.79, slope = 1.02). In healthy tissues, PET/MRI-derived SUVs were 16 ± 11% lower than on PET/CT (R (2) = 0.98, slope = 0.86). CONCLUSION: PET/MRI and PET/CT showed comparable performance with respect to calibration accuracy, image uniformity, and SUV recovery. [(18)F]FCH uptake values for both healthy tissues and lesions corresponded reasonably well between MR- and CT-based systems, but only in regions free of MR-based attenuation artifacts.

The use of PET-MRI in the follow-up after radiofrequency- and microwave ablation of colorectal liver metastases.

BACKGROUND: Thermal ablation of colorectal liver metastases (CRLM) may result in local progression, which generally appear within a year of treatment. As the timely diagnosis of this progression allows potentially curative local treatment, an optimal follow-up imaging strategy is essential. PET-MRI is a one potential imaging modality, combining the advantages of PET and MRI. The aim of this study is evaluate fluorine-18 deoxyglucose positron emission tomography (FDG) PET-MRI as a modality for detection of local tumor progression during the first year following thermal ablation, as compared to the current standard, FDG PET-CT. The ability of FDG PET-MRI to detect new intrahepatic lesions, and the extent to which FDG PET-MRI alters clinical management, inter-observer variability and patient preference will also be included as secondary outcomes. METHODS/DESIGN: Twenty patients undergoing treatment with radiofrequency or microwave ablation for (recurrent) CRLM will be included in this prospective trial. During the first year of follow-up, patients will be scanned at the VU University Medical Center at 3-monthly intervals using a 4-phase liver CT, FDG PET-CT and FDG PET-MRI. Patients treated with chemotherapy <6 weeks prior to scanning or with a contra-indication for MRI will be excluded. MRI will be performed using both whole body imaging (mDixon) and dedicated liver sequences, including diffusion-weighted imaging, T1 in-phase and opposed-phase, T2 and dynamic contrast-enhanced imaging. The results of all modalities will be scored by 4 individual reviewers and inter-observer agreement will be determined. The reference standard will be histology or clinical follow-up. A questionnaire regarding patients' experience with both modalities will also be completed at the end of the follow-up year. DISCUSSION: Improved treatment options for local site recurrences following CRLM ablation mean that accurate post-ablation staging is becoming increasingly important. The combination of the sensitivity of MRI as a detection method for small intrahepatic lesions with the ability of FDG PET to visualize enhanced metabolism at the ablation site suggests that FDG PET-MRI could potentially improve the accuracy of (early) detection of progressive disease, and thus allow swifter and more effective decision-making regarding appropriate treatment. TRIAL REGISTRATION NUMBER: NCT01895673.