Kazuto Kozaka

Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR Imaging--correlation with molecular transporters and histopathologic features.

PURPOSE To analyze the correlation between signal intensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance (MR) imaging and the expression of hepatocyte transporters with histopathologic features in hepatocellular carcinoma (HCC). MATERIALS AND METHODS Institutional ethics committee approval and informed consent were obtained. Forty surgically resected HCCs were classified as hypointense (n = 32) or iso- or hyperintense (n = 8) on the basis of findings in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging. The following were compared between hypointense and iso- or hyperintense HCCs: the time-signal intensity curves at gadoxetic acid-enhanced MR imaging, the expression levels of seven transporters (four organic anion-transporting polypeptides [OATPs] and three multidrug-resistant proteins [MRPs]) at polymerase chain reaction (PCR) (for 22 nodules), results of immunostaining of OATP8, and histologic features. Statistical analysis (unpaired t test, Mann-Whitney test, chi(2) test, and Fisher exact test) was performed for each result. RESULTS On the time-signal intensity curves, hypointense HCCs showed a decreasing pattern, whereas iso- or hyperintense HCCs showed an increasing pattern after the dynamic phase. PCR revealed that expression of OATP8 (an uptake transporter) in hypointense HCCs was lower and that in iso- or hyperintense HCCs was higher than in background liver (P < .001). The expression level of MRP3 (a sinusoidal export transporter) showed a similar trend to that of OATP8 (P < .001). Immunostaining revealed that OATP8 expression was weak in hypointense HCCs, whereas it was sustained in iso- or hyperintense HCCs (P < .001). At histologic examination, a pseudoglandular proliferation pattern with bile plugs was more commonly observed in iso- or hyperintense HCCs than in hypointense HCCs (P = .01 for proliferation patterns and P = .006 for bile plugs). CONCLUSION The enhancement ratio of HCCs in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging positively correlated with expression levels of OATP8 and MRP3, indicating that gadoxetic acid is taken up by OATP8 and excreted by MRP3.

The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging

ObjectivesTo clarify the changes in organic anion-transporting polypeptide 8 (OATP8) expression and enhancement ratio on gadoxetic acid-enhanced MR imaging in hepatocellular nodules during multistep hepatocarcinogenesis.MethodsIn imaging analysis, we focused on 71 surgically resected hepatocellular carcinomas (well, moderately and poorly differentiated HCCs) and 1 dysplastic nodule (DN). We examined the enhancement ratio in the hepatobiliary phase of gadoxetic acid enhanced MR imaging [(1/postcontrast T1 value−1/precontrast T1 value)/(1/precontrast T1 value)], then analysed the correlation among the enhancement ratio, tumour differentiation grade and intensity of immunohistochemical OATP8 expression. In pathological analysis, we focused on surgically resected 190 hepatocellular nodules: low-grade DNs, high-grade DNs, early HCCs, well-differentiated, moderately differentiated and poorly differentiated HCCs, including cases without gadoxetic acid-enhanced MR imaging. We evaluated the correlation between the immunohistochemical OATP8 expression and the tumour differentiation grade.ResultsThe enhancement ratio of HCCs decreased in accordance with the decline in tumour differentiation (P < 0.0001, R = 0.28) and with the decline of OATP8 expression (P < 0.0001, R = 0.81). The immunohistochemical OATP8 expression decreased from low-grade DNs to poorly differentiated HCCs (P < 0.0001, R = 0.15).ConclusionsThe immunohistochemical expression of OATP8 significantly decreases during multistep hepatocarcinogenesis, which may explain the decrease in enhancement ratio on gadoxetic acid-enhanced MR imaging.

Hepatocelluar nodules in liver cirrhosis: hemodynamic evaluation (angiography- assisted CT) with special reference to multi-step hepatocarcinogenesis

To understand the hemodynamics of hepatocellular carcinoma (HCC) is important for the precise imaging diagnosis and treatment, because there is an intense correlation between their hemodynamics and pathophysiology. Angiogenesis such as sinusoidal capillarization and unpaired arteries shows gradual increase during multi-step hepatocarcinogenesis from high-grade dysplastic nodule to classic hypervascular HCC. In accordance with this angiogenesis, the intranodular portal supply is decreased, whereas the intranodular arterial supply is first decreased during the early stage of hepatocarcinogenesis and then increased in parallel with increasing grade of malignancy of the nodules. On the other hand, the main drainage vessels of hepatocellular nodules change from hepatic veins to hepatic sinusoids and then to portal veins during multi-step hepatocarcinogenesis, mainly due to disappearance of the hepatic veins from the nodules. Therefore, in early HCC, no perinodular corona enhancement is seen on portal to equilibrium phase CT, but it is definite in hypervascular classical HCC. Corona enhancement is thicker in encapsulated HCC and thin in HCC without pseudocapsule. To understand these hemodynamic changes during multi-step hepatocarcinogenesis is important, especially for early diagnosis and treatment of HCCs.

A subgroup of intrahepatic cholangiocarcinoma with an infiltrating replacement growth pattern and a resemblance to reactive proliferating bile ductules: ‘bile ductular carcinoma’

Aims:  The histogenesis and biological behaviour of peripheral intrahepatic cholangiocarcinoma (peripheral CC) remain unclarified. The aim of this study was to examine the growth pattern of peripheral CC (24 cases) in comparison with hepatocellular carcinoma (HCC, 27 cases) and metastatic colorectal adenocarcinoma (MCA, 24 cases).

Hypervascular Hepatocellular Carcinoma: Correlation between Biologic Features and Signal Intensity on Gadoxetic Acid–enhanced MR Images

PURPOSE To analyze the correlation among biologic features, tumor marker production, and signal intensity at gadoxetic acid-enhanced MR imaging in hepatocellular carcinomas (HCCs). MATERIALS AND METHODS Institutional ethics committee approval and informed consent were obtained for this retrospective study. From April 2008 to September 2011, 180 surgically resected HCCs in 180 patients (age, 65.0 years ± 10.3 [range, 34-83 years]; 138 men, 42 women) were classified as either hypointense (n = 158) or hyperintense (n = 22) compared with the signal intensity of the background liver on hepatobiliary phase gadoxetic acid-enhanced MR images. Pathologic features were analyzed and a fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) production were compared by means of serum analysis and immunohistochemical staining. Recurrence and survival rates were also evaluated. The Mann-Whitney and Pearson correlation tests were used for statistical analysis. RESULTS The grade of differentiation was higher (P = .028) and portal vein invasion was less frequent in hyperintense HCCs (13.6%) than in hypointense HCCs (36.7%) (P = .039). The serum levels of AFP, Lens culinaris agglutinin reactive fraction of AFP, and PIVKA-II were lower in hyperintense than in hypointense HCCs (P = .003, .004, and .026, respectively). Immunohistochemical AFP and PIVKA-II expression were lower in hyperintense than in hypointense HCCs (both P < .001). The recurrence rate was lower in hyperintense than in hypointense HCCs (P = .039). CONCLUSION The results suggest that hyperintense HCCs on gadoxetic acid-enhanced MR images are less aggressive than hypointense HCCs. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120226/-/DC1.

Intrahepatic cholangiocarcinomas in cirrhosis are hypervascular in comparison with those in normal livers.

Intrahepatic cholangiocarcinomas (ICCs) are usually adenocarcinomas with fibrotic and hypovascular stroma. Intrahepatic cholangiocarcinomas in cirrhosis and precirrhotic liver (ICC‐cirrhosis) are increasingly being diagnosed, and can display hypervascluar enhancement resembling a hepatocellular carcinoma on dynamic imaging.

Relationship between signal intensity on hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MR imaging and prognosis of borderline lesions of hepatocellular carcinoma

PURPOSE To elucidate the incidence of signal intensity patterns of borderline lesions of hepatocellular carcinoma (HCC) on hepatobiliary phase Gd-EOB-DTPA (EOB) enhanced MRI and clarify the natural histories of these lesions. MATERIALS AND METHODS Total 99 borderline lesions of HCC were identified by angiography-assisted CT. The signal intensity of borderline lesions on hepatobiliary phase of EOB-enhanced MRI was analyzed. Progress rate from borderline lesions to hypervascular HCC was calculated with the Kaplan-Meier method among each signal intensity groups of nodules. RESULTS On hepatobiliary phase of EOB-enhanced MRI, 41.4% of the borderline lesions showed hypo-, 42.4% showed iso-, and 16.2% showed hyperintense, compared to background liver. Overall progress rates from borderline lesions to HCC were 10% in 1-year, 14% in 2-year and 20% in 3-year follow-up period. Progress rates to HCC in hypointense borderline lesions were 17% in 1-year, 28% in 2-year and 41% in 3-year follow-up period, and in isointense borderline lesions were 7% in 1-year, 7% in 2-year and 7% in 3-year follow-up period. No hyperintense borderline lesions progressed to HCC in follow-up period. CONCLUSION Although borderline lesions of HCC may show hypo-, iso- and hyperintensity on hepatobiliary phase of EOB-enhanced MRI, hypointense borderline lesions are high risk to progress HCC.

Transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma fed by the cystic artery.

PURPOSE To evaluate the safety, technical success rate, and effectiveness of transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC) fed by the cystic artery. MATERIALS AND METHODS Treatment of 27 tumors in 25 patients fed by the cystic artery was attempted with TACE. Twenty-two patients had previously undergone one to eight TACE sessions (mean, four sessions), and the duration after initiation of treatment of HCC was 4-69 months (mean, 24). In three patients, parasitization of the cystic artery was revealed at initial angiography. TACE was performed only when the microcatheter could be inserted into the tumor feeding branch and the stain of the gallbladder wall disappeared. The therapeutic effects and complications were retrospectively analyzed. RESULTS Seventeen tumors were completely fed by the cystic artery and 10 were fed by both the hepatic artery and cystic artery. Attenuation or occlusion of the hepatic artery was observed in 56%. The tumor feeding branch arising from the cystic artery could be successfully embolized in 18 tumors (67%) of 16 patients without severe complications. Adequate iodized oil accumulation was achieved in 14 tumors (52%) of 12 patients. Percutaneous therapy (n = 7), radiation (n = 4), and TACE after cholecystectomy (n = 1) were added for tumors with incomplete or unsuccessful TACE. Local progression was observed in three (21%) of 14 tumors treated by TACE alone during a mean follow-up period of 18 months. CONCLUSION TACE via the cystic artery was safe and technically possible in 67% of patients. If adequate iodized oil accumulation is obtained, which was only achieved in 52% of patients, sufficient therapeutic effect may be expected.

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic Acid-enhanced magnetic resonance imaging findings of borderline lesions at high risk for progression to hypervascular classic hepatocellular carcinoma.

Objectives: The objectives of the study were to assess the imaging features of hypovascular borderline lesions containing hypervascular foci on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and to evaluate the ability of Gd-EOB-DTPA-enhanced MRI to diagnose high-risk borderline lesions possibly consistent with early hepatocellular carcinoma (HCC). Methods: Institutional review board approval was obtained for this retrospective analysis of imaging findings, and informed consent was obtained from 217 consecutive patients undergoing Gd-EOB-DTPA-enhanced MRI and angiography-assisted computed tomography (CT) for examination of hepatocellular nodular lesions in cirrhotic livers. There were 73 nodules showing hypervascular foci in borderline lesions identified by angiography-assisted CT. Signal intensity patterns of the nodules were evaluated on hepatobiliary-phase Gd-EOB-DTPA-enhanced T1-weighted MRI obtained 20 minutes after intravenous injection of contrast media. Results: Among 73 high-risk borderline lesions, 59 were hypointense (81%), and 14 were isointense (19%), compared with background liver parenchyma. There were 27 untreated lesions followed by CT and/or MRI. Almost half of these nodules transformed into hypervascular HCC, regardless of signal intensities seen on hepatobiliary-phase Gd-EOB-DTPA-enhanced MRI. Conclusions: Although many high-risk borderline HCC lesions are hypointense on hepatobiliary-phase Gd-EOB-DTPA-enhanced MRI, some high-risk borderline lesions are isointense and transform at the same rate into hypervascular HCC.

MDCT findings of extrapancreatic nerve plexus invasion by pancreas head carcinoma: correlation with en bloc pathological specimens and diagnostic accuracy.

ObjectiveTo elucidate the multi-detector row computed tomography (MDCT) findings of extrapancreatic nerve plexus (PLX) invasion by pancreas head carcinoma (PhC) by “point-by-point” correlation with en bloc pathological specimens and to assess their diagnostic accuracy.MethodsEach pathological section of PhC and adjusted double oblique multiplanar reconstruction MDCT images were correlated in 554 sections from 37 patients. The diagnostic accuracy of the MDCT patterns derived was assessed by blind reading.ResultsPLX invasion with fibrosis showed mass or strand shape (85.6%) or coarse reticula (13.3%). The CT findings were divided into fine reticular and linear, coarse reticular, mass and strand, and nodular patterns. PLX invasion was revealed pathologically in 92% of the regions of investigation showing the mass and strand pattern and 63% of the coarse reticular pattern (all continuous with PhC), and they were highly suggestive of PLX invasion by PhC on MDCT images (p < 0.001). Sensitivity, specificity, accuracy, and positive and negative predictive values of these MDCT findings in the diagnosis of PLX invasion were 100% (25/25), 83.3% (10/12), 94.6% (35/37), 92.6% (25/27) and 100% (10/10), respectively.ConclusionThe mass and strand pattern and the coarse reticular pattern continuous with PhC on MDCT images were highly suggestive of PLX invasion by PhC.