Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2015; 21(15): 4583-4591
Published online Apr 21, 2015. doi: 10.3748/wjg.v21.i15.4583
Factors predicting aggressiveness of non-hypervascular hepatic nodules detected on hepatobiliary phase of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging
Tsutomu Kanefuji, Toru Takano, Takeshi Suda, Kouhei Akazawa, Takeshi Yokoo, Hiroteru Kamimura, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Hidefumi Aoyama, Minoru Nomoto, Shuji Terai
Tsutomu Kanefuji, Takeshi Suda, Deparatment of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma, Niigata 949-7302, Japan
Takeshi Yokoo, Hiroteru Kamimura, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Minoru Nomoto, Shuji Terai, Department of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata 951-8122, Japan
Toru Takano, Hidefumi Aoyama, Department of Radiation Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata 951-8122, Japan
Kouhei Akazawa, Department of Medical Informatics, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata 951-8122, Japan
Author contributions: Kanefuji T and Takano T contributed equally to this work; Suda T, Kanefuji T and Takano T designed the research; Yokoo T, Kamimura H, Kamimura K, Takamura M, Kawai H and Yamagiwa S performed the research; Tsuchiya A and Nomoto M made histological diagnosis; Takano T and Kanefuji T analyzed the data; Akazawa K performed statistical analyses; Suda T wrote the paper; and Aoyama H and Terai S supervised scientific accuracy of intellectual content.
Ethics approval: The study was reviewed and approved by the Niigata University Graduate School of Medical and Dental Sciences Institutional Review Board.
Informed consent: The institutional review board did not require informed consent for a retrospective study using medical records or imaging examinations.
Conflict-of-interest: There are no competing interests to disclose in relation to this study.
Data sharing: A supplementary table can be found at http://www.wjgnet.com/esps/ArticlePublishedOnlineDetail.aspx?id=13915.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Takeshi Suda, MD, PhD, Professor, Deparatment of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma, Niigata 949-7302, Japan. tspitt@med.niigata-u.ac.jp
Telephone: +81-25-7773200 Fax: +81-25-7772811
Received: September 7, 2014
Peer-review started: September 7, 2014
First decision: October 14, 2014
Revised: November 29, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: April 21, 2015
Abstract

AIM: To establish a prognostic formula that distinguishes non-hypervascular hepatic nodules (NHNs) with higher aggressiveness from less hazardous one.

METHODS: Seventy-three NHNs were detected in gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging (Gd-EOB-DTPA-MRI) study and confirmed to change 2 mm or more in size and/or to gain hypervascularity. All images were interpreted independently by an experienced, board-certified abdominal radiologist and hepatologist; both knew that the patients were at risk for hepatocellular carcinoma development but were blinded to the clinical information. A formula predicting NHN destiny was developed using a generalized estimating equation model with thirteen explanatory variables: age, gender, background liver diseases, Child-Pugh class, NHN diameter, T1-weighted imaging/T2-weighted imaging detectability, fat deposition, lower signal intensity in arterial phase, lower signal intensity in equilibrium phase, α-fetoprotein, des-γ-carboxy prothrombin, α-fetoprotein-L3, and coexistence of classical hepatocellular carcinoma. The accuracy of the formula was validated in bootstrap samples that were created by resampling of 1000 iterations.

RESULTS: During a median follow-up period of 504 d, 73 NHNs with a median diameter of 9 mm (interquartile range: 8-12 mm) grew or shrank by 68.5% (fifty nodules) or 20.5% (fifteen nodules), respectively, whereas hypervascularity developed in 38.4% (twenty eight nodules). In the fifteen shrank nodules, twelve nodules disappeared, while 11.0% (eight nodules) were stable in size but acquired vascularity. A generalized estimating equation analysis selected five explanatories from the thirteen variables as significant factors to predict NHN progression. The estimated regression coefficients were 0.36 for age, 6.51 for lower signal intensity in arterial phase, 8.70 or 6.03 for positivity of hepatitis B virus or hepatitis C virus, 9.37 for des-γ-carboxy prothrombin, and -4.05 for fat deposition. A formula incorporating the five coefficients revealed sensitivity, specificity, and accuracy of 88.0%, 86.7%, and 87.7% in the formulating cohort, whereas these of 87.2% ± 5.7%, 83.8% ± 13.6%, and 87.3% ± 4.5% in the bootstrap samples.

CONCLUSION: These data suggest that the formula helps Gd-EOB-DTPA-MRI detect a trend toward hepatocyte transformation by predicting NHN destiny.

Keywords: Hepatocellular carcinoma, Magnetic resonance imaging, Ethoxybenzyl moiety, Non-hypervascular hepatic nodule, Fate prediction

Core tip: This manuscript features a way of efficient prediction of fate for non-hypervascular hepatic nodules, which appear to be frequently detected after the introduction of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid in a magnetic resonance imaging study. A statistical analysis based on the interpretation of magnetic resonance imaging and regular clinicopathological factors lead to the development of a formula with an accuracy of 87.7% and 87.3% in the formulation and validation samples. Furthermore, the authors have developed a convenient application to evaluate the fate of non-hypervascular hepatic nodules through internet (http://www.med.niigata-u.ac.jp/in3/resident/NHN.html), which requires inputting only five factors.