title: Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography.
abstract: BACKGROUND
  Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an uncommon primary liver malignancy and little known about the clinical and imaging characteristics of cHCC-CC. We aim to define the demographics, imaging features of cHCC-CC on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CT) in this study.
  
  
  METHODS
  From January 2005 to December 2014, 45 patients with pathologically proven cHCC-CC who underwent preoperative CEUS and 43 patients who had additional CT scan in our institution were included. A retrospective review of the imaging studies and clinical data in these patients was conducted.
  
  
  RESULTS
  In our series, cHCC-CC accounted for 1.6 % of all primary liver malignancy. Mean age of patient with cHCC-CC was 52.8 year (range: 28-74 year) and 88.9 % (40/45) of patients were male. Thirty of forty five patients (66.7 %) had cirrhosis and 20 % (9/45) of patients had chronic hepatitis B without cirrhosis. Alpha--fetoprotein (AFP) was elevated in 62.2 % (28/45) of patients and carbohydrate antigen 19-9 (CA19-9) elevated in 22.2 % (10/45) of patients). Both AFP and CA19-9 were simultaneously elevated in 15.6 % (7/45) of patients. Enhancement pattern resembling cholangiocarcinoma (CC) was noted in 53.3 % (24/45) of patients (on CEUS and in 30.2 % (13/43) of patients at CT. Enhancement pattern resembling hepatocellular carcinoma (HCC) was observed in 42.2 % (19/45) of patients on CEUS and in 58.1 % (25/43) of patients at CT. The percentage of tumors showing CC enhancement pattern (27.9 %, 12/43) was comparable with that of tumors showing HCC enhancement pattern (44.2 %, 19/43) on both CEUS and CT (p = 0.116). Simultaneous elevation of tumor markers (AFP and CA19-9) or tumor marker elevation (AFP or CA19-9) in discordance with enhancement pattern on CEUS was demonstrated in 51.1 % (23/45) of patients and on CT in 53.5 % (23/43) of patients, which was significantly more than simultaneous elevation of tumor markers (AFP and CA19-9) alone (p = 0.000).
  
  
  CONCLUSIONS
  The clinical characteristics of cHCC-CC are similar to those of HCC. The cHCC-CC tumors display enhancement patterns resembling CC or HCC in comparable proportion on both CEUS and CT. Combination of simultaneous elevation of tumor makers (AFP and CA19-9) and tumor mark elevation (AFP or CA19-9) in discordance with presumptive imaging findings on CEUS or CT may lead significantly more patients to be suspicious of the diagnosis of cHCC-CC.
authors.affiliation: Department Hepato-biliary-Pancreatic Surgery, Southwest Hospital, Gaotangyan street, Shapingba, Chongqing, 400038, P. R China. raylee7991@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department Ultrasound, Southwest Hospital Affiliated to Third Military Medical University, Shapingba, Chongqing, 400038, P. R China. 846384842@qq.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department Ultrasound, Southwest Hospital Affiliated to Third Military Medical University, Shapingba, Chongqing, 400038, P. R China. tcl_hbl@126.com.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Tang
authors.affiliation: Department Radiology, Southwest Hospital Affiliated to Third Military Medical University, Shapingba, Chongqing, 400038, P. R China. pingc_ddd@sina.cm.
authors.forename: Ping
authors.initials: P
authors.lastname: Cai
authors.affiliation: Department Hepato-biliary-Pancreatic Surgery, Southwest Hospital, Gaotangyan street, Shapingba, Chongqing, 400038, P. R China. Makuansheng@vip.sina.com.
authors.forename: Kuan-Sheng
authors.initials: KS
authors.lastname: Ma
authors.affiliation: Department Radiology, Southwest Hospital Affiliated to Third Military Medical University, Shapingba, Chongqing, 400038, P. R China. Dingsy51@163.cm.
authors.forename: Shi-Yi
authors.initials: SY
authors.lastname: Ding
authors.affiliation: Department Ultrasound, Southwest Hospital Affiliated to Third Military Medical University, Shapingba, Chongqing, 400038, P. R China. wshospital_zxh@sina.com.
authors.forename: Xiao-Hang
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Department Pathology, Southwest Hospital Affiliated to Third Military Medical University, Shapingba, Chongqing, 400038, P. R China. gdy007@tmmu.edu.cn.
authors.forename: De-Yu
authors.initials: DY
authors.lastname: Guo
authors.affiliation: Department Pathology, Southwest Hospital Affiliated to Third Military Medical University, Shapingba, Chongqing, 400038, P. R China. yxcwq@163.com.
authors.forename: Xiao-Chu
authors.initials: XC
authors.lastname: Yan
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D015897:Comorbidity; D005260:Female; D006801:Humans; D007089:Image Enhancement; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014057:Tomography, X-Ray Computed / Q000379:methods; D047368:Tumor Burden; D014463:Ultrasonography / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor