Hepatocellular carcinomas with excessive copper accumulation: CT and MR findings.

Kitagawa, Kiyotaka; Matsui, Osamu; Kadoya, Masumi; Takashima, Tsutomu; Kawamori, Yasuhiro; Yamahana, Teruo; Kidani, Hisashi; Hirano, Masahiro; Masuda, Saeko; Nakanuma, Yasuni

doi:10.1148/radiology.180.3.1714611

Cited by 46 publications

(24 citation statements)

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“…Although few, however, there were several non-FNH nodules that showed high signal intensity on HBP. High signal intensity of one hypovascular hepatocellular nodule may be attributable to high signal intensity on precontrast T1-weighted image, which are sometimes observed in dysplatic nodules or early HCC, due to cooper or iron deposition [12][13][14] (Fig.2) or fatty metamorphosis [15]. Because EOB uptake have been reported to be almost constant regardless of the grade of HCC, if the precontrast signal intensity is high, that would be directly reflected on the SI on HBP [16].…”

Section: Discussionmentioning

confidence: 99%

“…In the early stages of multistep hepatocarcinogenesis [12,13], some hepatocelllar nodules including regenerative nodules (RN), dysplastic nodules (DN), early hepatocellular carcinomas (eHCC) or well differentiated hepatocellular carcinomas (wHCC), have been known to exhibit high signal intensity on T1WI, either related or unrelated to fatty metamorphosis [14][15][16][17]. Therefore, there could be a hypothesis that signal intensity before contrast administration may influence signal intensity on the postcontrast image.…”

Section: Assessmentmentioning

confidence: 99%

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Signal Intensity Characteristics of Liver Masses at Hepatobiliary Phase Images of Gadoxetate-Enhanced MR (EOB-MR): Qualitative Assessment

Sakamoto¹,

Shinagawa²,

Fujimitsu³

et al. 2012

Hepatocellular Carcinoma - Clinical Research

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Section: Discussionmentioning

confidence: 99%

Section: Assessmentmentioning

confidence: 99%

Signal Intensity Characteristics of Liver Masses at Hepatobiliary Phase Images of Gadoxetate-Enhanced MR (EOB-MR): Qualitative Assessment

Sakamoto¹,

Shinagawa²,

Fujimitsu³

et al. 2012

Hepatocellular Carcinoma - Clinical Research

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“…As for HCC, excessive Cu accumulation has been noticed in the human HCC samples. 28,29 No studies, however, have been performed to examine the effect of Cu on HCC development, except for a study on the Long-Evans Cinnamon (LEC) rat model of Wilson's disease. 42,43 LEC rat is a mutant strain, which consistently developed hepatitis and HCC.…”

Section: Discussionmentioning

confidence: 99%

“…21,28 Regarding HCC, it has been reported that excessive Cu level was found in the human HCC tissue as compared to the non-HCC regions. 28,29 In the present study, to elucidate the role of Cu and the feasibility of Cu-chelating agents in the future clinical applications, we examined the effect of the Cu-chelating agents, penicillamine and trientine, on tumor development and angiogenesis in the murine xenograft HCC model.…”

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confidence: 99%

The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells

et al. 2001

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Angiogenesis is now recognized as a crucial process in tumor development, including hepatocellular carcinoma (HCC). Since HCC is known as a hypervascular tumor, antiangiogenesis is a promising approach to inhibit the HCC development. Trientine dihydrochloride (trientine) is used in clinical practice as an alternative copper (Cu)-chelating agent for patients with Wilson's disease of penicillamine intolerance. In our study, we examined the effect of Cu-chelating agents on tumor development and angiogenesis in the murine HCC xenograft model. Although both trientine and penicillamine in the drinking water suppressed the tumor development, trientine exerted a more potent inhibitory effect than penicillamine. In combination with a Cu-deficient diet, both trientine and penicillamine almost abolished the HCC development. Trientine treatment resulted in a marked suppression of neovascularization and increase of apoptosis in the tumor, whereas tumor cell proliferation itself was not altered. In vitro studies also exhibited that trientine is not cytotoxic for the tumor cells. On the other hand, it significantly suppressed the endothelial cell proliferation. These results suggested that Cu plays a pivotal role in tumor development and angiogenesis in the murine HCC cells, and Cuchelators, especially trientine, could inhibit angiogenesis and enhance apoptosis in the tumor with consequent suppression of the tumor growth in vivo. Since trientine is already used in clinical practice without any serious side effects as compared to penicillamine, it may be an effective new strategy for future HCC therapy.

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“…The former type is diamagnetic and does not have unpaired electrons (17); therefore, it does not influence the MR signal unless extremely high concentrations are achieved (18). Divalent copper is paramagnetic and decreases T1 and T2 relaxation rates, an effect due to one unpaired electron (17).…”

Section: Coppermentioning

confidence: 99%

The Hypointense Liver Lesion on T2-Weighted MR Images and What It Means

Curvo-Semedo¹,

Brito²,

Seco³

et al. 2010

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).Abbreviations FNH = focal nodular hyperplasia, FSE = fast spin echo, HCC = hepatocellular carcinoma, SI = signal intensity. ABSTRACTThe vast majority of focal liver lesions are hyperintense on T2-weighted magnetic resonance (MR) images. Rarely, however, hepatic nodules may appear totally or partially hypointense on those images. Causes for this uncommon appearance include deposition of iron, calcium, or copper and are related to the presence of blood degradation products, macromolecules, coagulative necrosis, and other conditions. Although rare, low signal intensity relative to surrounding liver on T2-weighted images may be seen in a wide spectrum of lesions. Examples include cases of focal nodular hyperplasia, hepatocellular adenoma, hepatocellular carcinoma, metastases, leyomioma, siderotic or dysplastic nodules, nodules in Wilson disease, granuloma, and hydatid cyst. On fat-suppressed T2-weighted images, nodules with a lipomatous component, such as lipoma, angiomyolipoma, hepatocellular adenoma, and hepatocellular carcinoma may also appear partially or totally hypointense. The conjunction of other MR imaging findings and their integration in the clinical setting may allow a correct diagnosis in a considerable proportion of cases. The cause for T2-weighted hypointensity may not be, however, always recognized, and only pathologic correlation may provide the answer. The aims of this work are to discuss the causes and mechanisms of hypointensity of liver lesions on T2-weighted images and proposing an algorithm for classification that may be useful as a quick reminder for the interested reader. INTRODUCTIONMagnetic resonance (MR) imaging of liver lesions is of pivotal importance in clinical practice. In abdominal MR imaging, T1-and T2-weighted sequences remain a basic requirement for lesion characterization. MR signal intensity (SI) of focal liver lesions is affected by numerous pathologic factors. Histologic features strongly affect T1 and T2 relaxation times and MR imaging is unique in its ability to explore intracellular content and recognize the presence of substances that may govern signal behavior. Owing to their high cellular water content, the majority of focal liver lesions appear hyperintense on T2-weighted images. In contrast to this most frequently seen MR imaging pattern, liver nodules may show total or partial hypointensity on T2-weighted images. The hypointense appearance can be classified as absolute or relative, depending on the native SI of adjacent liver parenchyma and sequence parameters (Fig 1). Although relative hypointensity depends on the native SI of liver, which can be modified by several circumstances (eg, inflammation, diffuse iron deposition, etc), it may be more commonly encountered when

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Hepatocellular carcinomas with excessive copper accumulation: CT and MR findings.

Cited by 46 publications

References 0 publications

Signal Intensity Characteristics of Liver Masses at Hepatobiliary Phase Images of Gadoxetate-Enhanced MR (EOB-MR): Qualitative Assessment

Signal Intensity Characteristics of Liver Masses at Hepatobiliary Phase Images of Gadoxetate-Enhanced MR (EOB-MR): Qualitative Assessment

The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells

The Hypointense Liver Lesion on T2-Weighted MR Images and What It Means

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