Abstract
PurposeTo investigate the factors associated with hepatobiliary phase (HBP) enhancement at gadoxetic acid-enhanced magnetic resonance imaging (MRI) and to determine whether HBP images could be used to predict prognosis in patients with colorectal cancer liver metastasis (CRLM).ResultsOf the 96 total nodules, 65 and 31 nodules were in the mixed and clearly hypointense groups, respectively. In the 55 nodules without preoperative chemotherapy, organic anionic transporting polypeptide 1B3 (OATP1B3) expression was a significant factor regarding the HBP enhancement (P=0.042). In this subgroup, nodules with OATP1B3 expression displayed a significantly higher relative intensity ratio on the HBP image (RIRpost) and relative enhancement ratio (RER) than those lacking this marker (P=0.024, 0.003, respectively). No significant factor was associated with the enhancement pattern in the chemotherapy group. The mixed hypointense group displayed worse survival rates (P=0.002).Materials and MethodsNinety-six patients who underwent pre-operative liver MRI and surgical resection for CRLM from January 2010 to June 2012 were retrospectively analyzed. We qualitatively evaluated the HBP enhancement pattern of CRLMs and classified them into mixed and clearly hypointense groups. For quantitative measurement, the RIRpost and RER were analyzed. To investigate factors associated with HBP enhancement, tumor components (fibrosis, necrosis, and cellularity) and OATP1B3 expression were scored on a 4-point scale. Univariate and multivariate analyses were done to determine significant factors for visual enhancement and quantitative parameters.ConclusionsOATP1B3 expression is associated with mixed hypointense CRLMs without chemotherapy. Signal intensity on HBP has potential usefulness to predict prognosis in CRLMs.
Highlights
Colorectal cancer (CRC) is the third-most common cancer worldwide [1, 2]
To investigate factors associated with hepatobiliary phase (HBP) enhancement, tumor components and organic anionic transporting polypeptide 1B3 (OATP1B3) expression were scored on a 4-point scale
OATP1B3 expression is associated with mixed hypointense cancer liver metastasis (CRLM) without chemotherapy
Summary
Hepatic metastases from CRC are an important clinical problem because the liver is the most frequent site of metastasis, and their presence can significantly change the treatment plan and outcome [3]. Gadoxetic acid-enhanced MRI is an established method widely used for the evaluation of colorectal cancer liver metastasis (CRLM) because the hepatobiliary phase (HBP) offers excellent lesion to liver contrast, leading to a higher lesion detection rate [4]. Gadoxetic acid is a liver-specific MRI contrast agent whose uptake is mediated by the organic anionic transporting polypeptide 1B3 (OATP1B3) expressed by hepatocytes. The general belief has been that tumors of non-hepatocyte origin, including CRLMs, could not actively uptake gadoxetic acid and, lacked a T1 contrast effect on the HBP [5]. A recent study reported that 72% of CRLMs show mixed signal intensity (SI) on HBP, vaguely assumed to be the result of gadoxetic acid retention within the extracellular space where abundant desmoplasia and intraacinar necrosis exist [6], but the underlying mechanism remains poorly understood
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