title: Lack of arterial hypervascularity at contrast-enhanced ultrasound should not define the priority for diagnostic work-up of nodules <2 cm.
abstract: OBJECTIVE
  Current guidelines recommend diagnostic work-up for nodules >1cm detected during screening for hepatocellular carcinoma (HCC). This implies that patients with benign conditions may undergo unnecessary evaluation and those with small nodules may be intervened too early, leading to overdiagnosis. Since increased arterial vascularization is the hallmark of malignancy, its detection by contrast-enhanced ultrasound (CEUS) could become the signal to proceed with diagnosis confirmation. The aim was to assess if HCCs <2 cm without arterial hyperenhancement by baseline CEUS have a benign evolutionary profile, suggesting that diagnosis and invasive treatment could be delayed until detection of an overt malignant profile, associated with increased vascularization.
  
  
  METHODS
  We prospectively included 168 cirrhotic patients with a newly detected solitary nodule of 5-20mm by screening ultrasonography. MRI, CEUS and fine needle biopsy (FNB) were performed and if no confident diagnosis was obtained, patients were closely followed to rule out HCC. Final diagnosis was: HCC (n = 119), cholangiocarcinoma (n = 3), neuroendocrine tumour (n = 1) and benign lesions (n = 45).
  
  
  RESULTS
  CEUS did not detect contrast hyperenhancement in the arterial phase in 55 cases (34%). Eighteen out of these 55 nodules were diagnosed as HCC. Non-CEUS hyperenhanced HCCs were more frequently well-differentiated than CEUS-hyperenhanced HCCs (p < 0.004). Fourteen patients were treated with ablation and 4 with resection. Ten (55.6%) patients experienced tumour recurrence after treatment, mostly distant, confirming their overt malignant profile.
  
  
  CONCLUSIONS
  Absence of contrast hyperenhancement on CEUS during the arterial phase in nodules <2 cm in a cirrhotic liver does not predict a less malignant profile. Accordingly, priority for diagnostic work-up and treatment should not differ according to contrast profiles on CEUS.
authors.affiliation: Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Forner
authors.affiliation: Radiology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Vilana
authors.affiliation: Radiology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Bianchi
authors.affiliation: Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodríguez-Lope
authors.affiliation: Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Reig
authors.affiliation: Radiology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: García-Criado
authors.affiliation: Radiology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rimola
authors.affiliation: Pathology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Solé
authors.affiliation: Radiology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.affiliation: Radiology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Concepció
authors.initials: C
authors.lastname: Bru
authors.affiliation: Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. Electronic address: jbruix@clinic.ub.es.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
mesh_terms: D044963:Biopsy, Fine-Needle; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D003287:Contrast Media; D003937:Diagnosis, Differential; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging* / Q000473:pathology; D008113:Liver Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000473:pathology; D011446:Prospective Studies; D014463:Ultrasonography
chemical_list: D003287:Contrast Media
keywords: Cirrhosis; Contrast-enhanced ultrasonography; Diagnosis; Dynamic imaging techniques; Hepatocellular carcinoma