High-signal-intensity MR Image in the Hepatobiliary Phase Predicts Long-term Survival in Patients With Hepatocellular Carcinoma

Patients and Methods

Between 2008 and 2013, a total of 257 patients with Child-pugh class A and single HCC or 2 nodules HCC were retrospectively identified from 5 medical university hospitals. Of those, 21 patients showed uncommon high-SI image in the HB phase on Gd-EOB-DTPA-enhanced MRI (Figure 1a and 1b). The patients comprised 16 men (76%) and 5 women (24%), and the median age was 71 years (range=55-82 years). All patients were given a diagnosis of HCC preoperatively because they showed typical HCC images (high density in the arterial phase and low density in the venous phase) on multidetector computed tomography (MDCT) or dynamic MRI. Of the 21 patients, 17 (81%) were given diagnoses of single HCC and 4 (19%) were given diagnoses of two nodular HCCs. The median tumor size on CT scan was 3.5 cm (range=1-10 cm). No patients showed major vascular invasion of HCC.

To determine the prognostic impact of the high-SI image HCC in the HB phase, 215 patients with typical low-SI image HCC in the HB phase were also evaluated (Figure 1c). All those 215 patients showed Child-Pugh class A, typical HCC images, single or 2 nodules, median tumor size of 3.2 cm, and no major vascular invasion of HCC. The remaining 21 patients with heterogeneous mixed (high and low)-SI image HCC were also evaluated (Figure 1d).

This study was proposed by the association for clinical research on surgery (ACRoS-1401) of 5 medical university hospitals. Information of this study was obtained by opt-out for all patients because this study was a retrospective cohort study. The local committees for medical ethics and clinical studies of each of the 5 medical universities approved this study. The ethics committee of TWMU approved this study (approval number: 3084).

Gd-EOB-DTPA-enhanced MRI. MRI was performed according to the protocol of each hospital. All patients received a dose of 0.1 ml/kg Gd-EOB-DTPA (Primovist; Bayer Schering Pharma AG, Berlin, Germany) intravenously at a rate of 1 ml/sec. Dynamic studies (arterial dominant phase, portal phase, venous phase, and equilibrium phase) and HB phase images were taken at 15-20 min after the injection (4).

Signal intensity (SI) within the tumor in the HB phase was classified into high-SI, low-SI, or mixed-SI HCC. Tumors that showed a homogenous high-SI within the tumor in the HB phase compared with that of the liver parenchyma and determined to be high-SI image HCC (Figure 1a, b). On the other hand, tumors that showed a homogenous low-SI within the tumor were determined to be low-SI image HCC (Figure 1c). Tumors that showed a heterogeneous high- and low-SI within the tumor were determined mixed-SI image HCC (Figure 1d). The relative SI within the tumor was also assessed as follows; the SI of the tumor and liver parenchyma were measured on the same image using oval regions of interest (ROI). The relative SI was calculated as follows: Relative SI=SI tumor/SI liver parenchyma (9). These findings were determined by all authors who had over 15 years of experience in liver surgery and a radiologist with 20 years of experience in radiological diagnosis.

Surgery and pathological evaluation. All patients underwent hepatectomy within 2 weeks after Gd-EOB-DTPA-enhanced MRI at each of the 5 university hospitals. Sixteen of 21 patients with high-SI HCC underwent anatomical hepatectomy, and 5 patients underwent non-anatomical partial resection. The choice of resection was made on the basis of the tumor location and liver function (ICGR15). No mortality was seen in the 21 patients with high-SI HCC. Macroscopic morphology of tumor type and pathological findings were examined according to the General Rules for the Clinical and Pathological Study of Primary Liver Cancer of the Liver Cancer Study Group of Japan (13). The terminology of liver resection was determined based on the Terminology Committee of the International Hepato-Pancreato-Biliary Association in 2000 (14).

Follow-up and treatment of patients with recurrence. After surgery, patients were followed up every 4-12 weeks at the 5 university hospitals, and the mean follow-up period was 45±28 months (range=0.7-112 months). Ultrasonography or CT was performed once every 3-4 months. Cause-specific survival was defined as the time from hepatectomy to the date of cancer-death, liver failure-death or last contact. When a solitary HCC recurred in the liver, hepatectomy was repeated or radiofrequency ablation was performed. When multiple HCCs recurred in the liver, transarterial chemoembolization (TACE) was performed.

Statistical analysis. Categorical variables were assessed using the chi-square test or Fisher exact test, and continuous variables were assessed using the t-test. Continuous variables were divided into two groups according to the median value (Age, ICGR15, and tumor size) and normal cut off value (AFP and PIVKA-II). Patient overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan–Meier method, and comparison of survival curves was made with the log-rank test. Potential predictors of OS and RFS were evaluated in a multivariate Cox's proportional hazard model. p-Values less than 0.05 (p<0.05) were taken to indicate statistical significance. JMP software (version 13.0; SAS Institute, Cary, NC, USA) was used for statistical analysis.