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Purpose: This prospective single-centre phase II trial assessed the diagnostic impact of (18)F-FDG PET-CT in the evaluation of solid pancreatic lesions (phi >or= 10 mm) compared to endosonography (EUS), endoscopic retrograde cholangio-pancreatography (ERCP) with intraductal ultrasound (IDUS), abdominal ultrasound (US) and histopathological reference., Methods: Forty-six patients (32 men/14 women, phi 61.7 years) with suspected pancreatic neoplasms underwent PET-CT with contrast-enhanced biphasic multi-detector CT of the upper abdomen followed by a diagnostic work-up with EUS, ERCP with IDUS and US within 3 weeks. PET-CT data sets were analysed by two expert readers in a consensus reading. Histology from surgery, biopsy/fine-needle aspiration and/or clinical follow-up >or=12 months served as standard of reference., Results: Twenty-seven pancreatic malignancies were histopathologically proven; 19 patients had benign diseases: 36/46 lesions (78%) were detected in the head of the pancreas, 7/46 and 3/46 in the body and tail region, respectively. Sensitivity and specificity of PET-CT were 89% and 74%, respectively; positive predictive value (PPV) and negative predictive value (NPV) were 83% and 82%, respectively. Sensitivity (81-89%), specificity (74-88%), PPV (83-90%) and NPV (77-82%) achieved by EUS, ERCP and US were not significantly different. PET analysis revealed significantly higher maximum mean standardised uptake values (SUV(max) 6.5+/-4.6) in patients with pancreatic malignancy (benign lesions: SUV(max) 4.2+/-1.5; p<0.05). PET-CT revealed cervical lymphonodal metastasis from occult bronchogenic carcinoma and a tubular colon adenoma with intermediate dysplasia on polypectomy, respectively., Conclusions: (18)F-FDG PET-CT achieves a comparably high diagnostic impact evaluating small solid pancreatic lesions versus conventional reference imaging modalities. Additional clinical diagnoses are derived from concomitant whole-body PET-CT imaging.