title: Diffuse infiltrative hepatocellular carcinoma: assessment of presentation, treatment, and outcomes.
abstract: BACKGROUND
  Data on infiltrating hepatocellular carcinoma (HCC) are limited. We sought to define treatment and outcome of patients treated with infiltrating HCC compared with patients who had advanced multifocal HCC.
  
  
  METHODS
  Between January 2000 and July 2011, a total of 147 patients with advanced HCC were identified from the Johns Hopkins Hospital database (infiltrative, n = 75; multifocal, n = 72). Clinicopathologic data were compared by HCC subtype.
  
  
  RESULTS
  Patients with infiltrating HCC had higher alfa-fetoprotein levels (median infiltrative, 326.5 ng/mL vs. multifocal, 27.0 ng/mL) and larger tumors (median size, infiltrating, 9.2 cm vs. multifocal, 5.5 cm) (P < 0.05). Imaging failed to reveal a discrete lesion in 42.7 % of patients with infiltrating HCC. Most infiltrating HCC lesions presented as hypointense on T1-weighted images (55.7 %) and hyperintense on T2-weighted images (80.3 %). Among patients with infiltrating HCC, most (64.0 %) were treated with intra-arterial therapy (IAT), and periprocedural morality was 2.7 %. Patients treated with IAT had longer survival versus patients receiving best support care (median survival, IAT, 12 months vs. best supportive care, 3 months; P = 0.001). Survival after IAT was similar among patients treated with infiltrating HCC versus multifocal HCC (hazard ratio 1.29, 95 % confidence interval 0.82-2.03; P = 0.27). Among infiltrating HCC patients, pretreatment bilirubin >2 mg/dL and alfa-fetoprotein >400 ng/mL were associated with worse survival after IAT (P < 0.05). Patients with progressive disease after IAT had higher risk of death versus patients who had stable/responsive disease (hazard ratio 3.53, 95 % confidence interval 1.49-8.37; P = 0.004).
  
  
  CONCLUSIONS
  Patients with infiltrative HCC often present without a discrete lesion on imaging. IAT for infiltrative HCC was safe and was associated with survival comparable to IAT outcomes for patients with multifocal HCC. Infiltrative HCC morphology is not a contraindication to IAT therapy in select patients.
authors.affiliation: Department of Surgery, Liver Tumor Center, Johns Hopkins University School of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kneuertz
authors.forename: Aram
authors.initials: A
authors.lastname: Demirjian
authors.forename: Amin
authors.initials: A
authors.lastname: Firoozmand
authors.forename: Celia
authors.initials: C
authors.lastname: Corona-Villalobos
authors.forename: Nikhil
authors.initials: N
authors.lastname: Bhagat
authors.forename: Joseph
authors.initials: J
authors.lastname: Herman
authors.forename: Andrew
authors.initials: A
authors.lastname: Cameron
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gurakar
authors.forename: David
authors.initials: D
authors.lastname: Cosgrove
authors.forename: Michael A
authors.initials: MA
authors.lastname: Choti
authors.forename: Jean-Francois H
authors.initials: JF
authors.lastname: Geschwind
authors.forename: Ihab R
authors.initials: IR
authors.lastname: Kamel
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001663:Bilirubin / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000473:pathology* / Q000628:therapy*; D016461:Chemoembolization, Therapeutic; D018450:Disease Progression; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology* / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011169:Portal Vein; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D013927:Thrombosis / Q000150:complications; D014057:Tomography, X-Ray Computed; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D000509:alpha-Fetoproteins; D001663:Bilirubin