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The use of standardized terms in assessing and reporting disease processes has well-established benefits, such as clear communication between radiologists and other health care providers, improved diagnostic accuracy and reproducibility, and the enhancement and facilitation of research. Recently, the Liver Imaging Reporting and Data System (LI-RADS) Steering Committee released a universal liver imaging lexicon. The current version of the lexicon includes 81 vetted and precisely defined terms that are relevant to acquisition of images using all major liver imaging modalities and contrast agents, as well as lesion- and organ-level features. Most terms in the lexicon are applicable to all patients undergoing imaging of the liver, and only a minority of the terms are strictly intended to be used for patients with high risk factors for hepatocellular carcinoma. This pictorial atlas familiarizes readers with the liver imaging lexicon and includes discussion of general concepts, providing sample definitions, schematics, and clinical examples for a subset of the terms in the liver imaging lexicon. The authors discuss general, technical, and imaging feature terms used commonly in liver imaging, with the goal of illustrating their use for clinical and research applications.

We report a rare case of intrahepatic cholangiocarcinoma (iCCA) that arose from a simple hepatic cyst. A 72-year-old man was transferred to our hospital for treatment of a liver tumor. Dynamic contrast-enhanced computed tomography (CT) detected a small tumor surrounding a hepatic cyst in segment 8 that showed low attenuation on a pre-contrast CT, rim-like enhancement in the arterial dominant phase, and delayed enhancement in the delayed phase. On gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced dynamic magnetic resonance imaging (MRI), the hepatic tumor had hypointensity on T1-weighted images, hyperintensity on T2-weighted images, hyperintensity on diffusion-weighted images, and hypointensity on the hepatobiliary phase. The tumor increased in size after 6 months, and partial hepatectomy was performed. Histopathologically, the tumor was consistent with moderately to poorly differentiated adenocarcinoma with the microscopic lymphatic, portal, and hepatic venous invasion. The epithelium of the cystic region largely comprised carcinoma in situ, with dysplastic biliary epithelial cells and a small portion of normal biliary epithelial cells. The transition from carcinoma in situ to invasive carcinoma was confirmed, and the patient was diagnosed with iCCA arising from a hepatic cyst via dysplasia and carcinomatous transformation.

Hepatocellular carcinoma (HCC) is a malignancy with variable biologic aggressiveness based on the tumor grade, presence or absence of vascular invasion, and pathologic and molecular classification. Knowledge and understanding of the prognostic implications of different pathologic and molecular phenotypes of HCC are emerging, with therapeutics that promise to provide improved outcomes in what otherwise remains a lethal cancer. Imaging has a central role in diagnosis of HCC. However, to date, the imaging algorithms do not incorporate prognostic features or subclassification of HCC according to its biologic aggressiveness. Emerging data suggest that some imaging features and further radiologic, pathologic, or radiologic-molecular phenotypes may allow prediction of the prognosis of patients with HCC.

Background Imaging markers of hepatocellular carcinoma (HCC) on the basis of molecular classification are important for predicting malignancy grade and prognosis. P53-mutated HCC is a major aggressive subtype; however, its imaging characteristics have not been clarified. Purpose To clarify the imaging characteristics of P53-mutated HCC at dynamic CT and gadoxetic acid-enhanced MRI that are correlated with its clinical features, pathologic findings, and prognosis. Materials and Methods In this retrospective single-center study, patients with surgically resected HCC between January 2015 and May 2018 in a university hospital were evaluated. HCC was classified into P53-mutated HCC and non-P53-mutated HCC using immunostaining. Dynamic CT and gadoxetic acid-enhanced MRI findings, clinical features, pathologic findings, and prognosis were compared using Mann-Whitney test, χ

Indocyanine green (ICG) excretory defect is characterized by an ICG retention rate of more than 50% at 15 min without any other abnormal liver functions. The incidence of ICG excretory defect is 0.007% in the Japanese population. Due to its rarity, the imaging characteristics associated with ICG excretory defect remain unclear. Herein, we present three cases of ICG excretory defect, which showed impaired lesion detectability on gadoxetic acid-enhanced MR imaging (EOB-MRI). In the hepatobiliary phase (HBP) of EOB-MRI, diminished enhancement of the liver parenchyma, prolonged intravascular enhancement, and attenuated gadoxetic acid excretion to the bile duct were observed. Our study also investigated the expression level of organic anion transporting polypeptide (OATP) 1B3 and OATP1B1/1B3, which is related to the uptake of ICG and gadoxetic acid into hepatocytes. All cases showed decreased expression of OATP1B3, which was assumed to be characteristic of ICG excretory defect. The present study indicates that, when patients with ICG excretory defect are evaluated using EOB-MRI, attention should be paid to the impaired lesion detectability in the HBP due to the attenuated gadoxetic acid uptake into the liver parenchyma.

Background and Aims: Hepatobiliary phase-hypointense nodules without arterial phase hyperenhancement (HHNs without APHE) on gadolinium-ethoxybenzyl-diethylenetriamine-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) are considered to be dysplastic nodules or early hepatocellular carcinoma (HCC) and have high risk of undergoing malignant transformation and progression to hypervascular HCC. The aim of this study was to evaluate the clinical outcome of HHNs without APHE diagnosed by Gd-EOB-DTPA-enhanced MRI before the eradication of HCV by direct-acting antiviral agents (DAAs). Methods: We retrospectively investigated 221 consecutive patients with HCV infection who were treated with DAAs. Thirty patients with 65 HHNs without APHE were enrolled in a sustained virologic response (SVR) cohort and 22 with 43 HHNs without APHE who did not receive DAAs or had failed HCV eradication therapy were enrolled in a non-SVR cohort. Fifty-seven percent of patients in the SVR group and 64% of those in the non-SVR group had a history of HCC. The primary endpoint of this study was the development of hypervascular HCC from HHNs without APHE detected on imaging. The cumulative incidence and relative risk of progression to hypervascular HCC in relation to clinical characteristics were compared between the two cohorts. Results: The 2-year cumulative incidence of progression to hypervascular HCC was 8.5 and 21.9% in the SVR and non-SVR cohorts, respectively. There was a significant reduction in progression of HHNs without APHE to HCC after the eradication of HCV (p = 0.022, log-rank test). Multivariate Cox regression analysis identified hyperintensity on T2-weighted images (relative risk 14.699, p < 0.001) and achieving SVR (relative risk 0.290, p = 0.043) as independent factors associated with the risk of HCC. During follow-up, 6 (9.2%) of the HHNs without APHE in the SVR cohort became undetectable on hepatocyte-phase images. Conclusions: Eradication of HCV by DAAs could reduce the hypervascularization rate of HHNs without APHE, and some of these nodules disappeared.

Background Massive arterioportal fistula (APF) is naturally irreversible and can induce portal hypertension and portal vein thrombosis (PVT), worsening survival outcomes. Purpose To evaluate the clinical course and details of transarterial embolization (TAE) procedures for massive APF. Material and Methods This retrospective single-center observational study evaluated the time until embolization after puncture, imaging, embolization methods, and laboratory data of 10 consecutive patients who were diagnosed with massive APF after puncture and underwent TAE at our hospital from 1 April 2012 to 30 September 2019. Results Out of 10 cases, eight demonstrated a simple type and the other two cases a complex network type on the digital subtraction angiography pattern of massive APF. In two simple-type cases for which re-embolization was required, other subsegmental branches were embolized. The two cases showing a complex network type had been embolized via not only the subsegmental branch, but also the extrahepatic and multiple subsegmental branches. Child–Pugh scores were improved in eight of the ten cases. PVT was seen in six cases before embolization, but disappeared after embolization in all cases, despite the fact that three cases had not received anticoagulant therapy. Six cases had digestive varices before embolization, suggesting portal hypertension, and two of the six cases with esophageal varices and one with gastric varices decreased after embolization. Conclusion TAE for massive APF contributed to the improvement of hepatic reserve, the disappearance of PVT, and the improvement of portal hypertension; however, embolization of multiple branches may still be required in some cases.

Hepatocellular carcinoma (HCC) is heterogeneous in terms of its biological nature. Various factors related to its biological nature, including size, multifocality, macroscopic morphology, grade of differentiation, macro/microvascular invasion, bile duct invasion, intra-tumoral fat and molecular factors, and their value as prognostic imaging biomarkers have been reported. And recently, genome-based molecular HCC classification correlated with clinical outcome has been elucidated. The imaging biomarkers suggesting a less aggressive nature of HCC are smaller size, solitary tumor, smooth margin suggesting small nodular type with indistinct margin and simple nodular type with distinct margin, capsule, imaging biomarkers predicting early or well-differentiated grade, intra-tumoral fat detection, and low fluorodeoxyglucose (FDG) accumulation. The imaging biomarkers suggesting an aggressive HCC nature are larger size, multifocality, non-smooth margin suggesting simple nodular type with extranodular growth, confluent multinodular, and infiltrative type, imaging biomarkers predicting poor differentiation, macrovascular tumor thrombus, predicting microvascular invasion imaging biomarkers, bile duct dilatation or tumor thrombus, and high FDG accumulation. In the genome-based molecular classification, CTNNB-1 mutated HCC shows a less aggressive nature, while CK19/EpCAM positive HCC and macrotrabecular massive HCC show an aggressive one. Better understanding of these imaging biomarkers can contribute to devising more appropriate treatment plans for HCC.

To identify imaging features that assist in discriminating intraductal papillary neoplasms of the bile duct (IPNBs) from papillary cholangiocarcinomas (PCCs).This study was approved by the institutional review board. Using the recently proposed histological diagnostic criteria for biliary papillary neoplasms, IPNBs and PCCs were selected from 537 biliary neoplasms consecutively resected in a 12.5-year period. Clinical and imaging features were compared between the two groups.The histology review identified 19 IPNBs and 48 PCCs, representing an estimated prevalence of IPNBs among biliary neoplasms of 4%. Approximately one half of IPNBs were incidentally found on imaging conducted for other purposes. In terms of tumor location, 15/19 IPNBs (79%) developed in intrahepatic bile ducts, and 41/48 PCCs (85%) in the distal bile duct. Cystic appearance was highly suggestive for IPNBs (p 0.001). Using these two parameters, 78% of papillary bile duct neoplasms could be classified into IPNBs or PCCs. Other imaging findings favoring IPNBs included frond-like mural nodule, downstream bile duct dilatation, and the lack of abnormal enhancement in the adjacent bile duct. Interestingly, two patients with non-invasive or microinvasive IPNB had undergone abdominal imaging studies 3 years before, and a retrospective review of the previous images identified small nodular or cystic lesions, suggesting a less progressive nature of IPNBs than currently thought.Imaging findings useful for discriminating IPNBs from PCCs appear to be tumor location, shape of tumor, appearance of mural nodules, duct dilatation at unaffected duct, and abnormal enhancement of the adjacent bile duct.• Intrahepatic location and cystic dilatation of the affected bile duct are the strong discriminators between IPNBs and PCCs. • The shape of the mural nodule and appearance of the neighboring bile duct are helpful for distinguishing IPNBs and PCCs. • The less aggressive behavior of IPNBs compared with PCCs may facilitate less invasive management in patients with IPNB.

Objectives To clarify the ultrasonographic features of immunoglobulin G4 (IgG4)-related dacryoadenitis and sialadenitis (IgG4-DS) and their usefulness in clinical diagnostic sessions. Methods By re-evaluating 96 consecutive patients with IgG4-related disease, we identified 54 patients (male:female = 37:17; median age, 69.5 years) who underwent lacrimal or submandibular gland (LG or SG, respectively) ultrasonography and computed tomography (CT). Their clinical and ultrasonographic features were retrospectively analysed. Radio-pathological correlations were also examined in LG (23 cases) and SG lesions (20 cases). Additionally, the diagnostic accuracy of CT for LG/SG lesions was evaluated. Results Abnormal ultrasonographic findings were detected in 33 (LGs) and 38 (SGs) patients, and most of them were observed bilaterally. All lesions were well demarcated and demonstrated diffuse low-echoic areas (rocky pattern) or multiple low-echoic nodules surrounded by high-echoic linear shadows (cobblestone pattern) corresponding to intra-lobular inflammation and inter-lobular fibrosis. Moreover, 42% (LGs; 14/33) and 42% (SGs; 16/38) patients had glandular lesions without clinical symptoms associated with the affected glands. The diagnostic accuracy of CT was ∼80% for LG and 55% for SG. Conclusions Ultrasonographic findings in IgG4-DS included diffuse or nodular low-echoic areas with linear high-echoic structures corresponding to inflamed lobules and inter-lobular fibrosis. These findings can help detect IgG4-DS.

Backgrounds and aims Structural dynamics of basement membrane components remained to be elucidated in the process of hepatocarcinogenesis. We evaluated the characteristics of hepatocellular carcinoma (HCC) expressing laminin γ2 monomer (LG2m), a previously unrecognized basement membrane component not detected in normal tissues, for HCC diagnosis. We further determined if elevated serum LG2m is a risk factor for HCC development in patients with chronic hepatitis C (CHC). Approach and results In HCC cell lines, LG2m was expressed in alpha-fetoprotein-negative cluster of differentiation 90-positive cells characterized by highly metastatic natures. Using 14 cell lines and 258 HCC microarray data, we identified that LG2m gene signature was associated with Hoshida's S1/Boyault's G3 molecular subclasses with poor prognosis, which could not be recognized by alpha-fetoprotein. Serum LG2m was assessed in 24 healthy donors, 133 chronic liver disease and 142 HCC patients, and sensitivity and specificity of LG2m testing for HCC diagnosis were 62.9% and 70.5%, respectively (cutoff: 30pg/ml). We evaluated the consequence of LG2m elevation in two independent HCC cohorts (n = 47 and n = 81), and LG2m-high HCC showed poor prognosis with later development of distant organ metastasis (cutoff: 60pg/ml). LG2m was slightly elevated in a subset of CHC patients, and Kaplan-Meier analysis indicated a high incidence of HCC (n = 70). For validation, we enrolled 399 CHC patients with sustained virological response (SVR) as a multicenter prospective study, and serum LG2m elevation correlated with a high incidence of HCC in the CHC patients with SVR (P Conclusions LG2m is a novel predictive biomarker for the development of metastatic HCC. Elevated serum LG2m is a HCC risk in CHC patients who have achieved SVR.

Background and Objectives: Although cholangiolocellular carcinoma is considered a combined hepatocellular and cholangiocarcinoma, we feel that this classification is not appropriate. Therefore, we compared the diagnostic imaging findings, surgical prognosis, and pathological features of cholangiolocellular carcinoma with those of other combined hepatocellular and cholangiocarcinoma subtypes, hepatocellular carcinoma, and cholangiocarcinoma. Methods: The study patients included 7 with classical type combined hepatocellular and cholangiocarcinoma; 8 with stem cell feature, intermediate type combined hepatocellular and cholangiocarcinoma; 13 with cholangiolocellular carcinoma; 58 with cholangiocarcinoma; and 359 with hepatocellular carcinoma. All patients underwent hepatectomy or living-related donor liver transplantation from 2001 to 2014. Results: cholangiolocellular carcinoma could be distinguished from hepatocellular carcinom, other combined hepatocellular and cholangiocarcinoma subtypes, and cholangiocarcinoma by the presence of intratumoral Glisson’s pedicle, hepatic vein penetration, and tumor-staining pattern on angiography-assisted CT. Cholangiolocellular carcinoma was associated with a significantly lower SUV-max than that of cholangiocarcinoma on FDG-PET. Hepatocellular carcinoma, classical type, and cholangiolocellular carcinoma had significantly better prognoses than stem cell feature, intermediate type and cholangiocarcinoma. A cholangiocarcinoma component was detected in cholangiolocellular carcinoma that progressed to the hepatic hilum, and the cholangiocarcinoma component was found in perineural invasion and lymph node metastases. Conclusions: From the viewpoint of surgeon, cholangiolocellular carcinoma should be classified as a good-prognosis subtype of biliary tract carcinoma because of its tendency to differentiate into cholangiocarcinoma during its progression, and its distinctive imaging and few recurrence rates different from other combined hepatocellular and cholangiocarcinoma subtypes.

Background/aim CBP is a transcriptional coactivator in the Wnt/β-catenin pathway that is related to cell kinetics and differentiation. This study aimed to characterize β-catenin-activated hepatocellular carcinoma (HCC) and evaluate the direct effects of PRI-724 (a selective inhibitor of Wnt/β-catenin/CBP signaling) on HCC. Materials and methods Immunohistochemistry for β-catenin was performed in 199 HCC resected samples. Moreover, using cultured HCC cell lines, cell kinetics and its related proteins were analyzed after treatment of cells with C-82 (active form of PRI-724). Results Nuclear β-catenin expression was found in 18% of HCC cases and the tumor sizes in these positive samples were larger. In HCC cell lines with a constitutively activated β-catenin, C-82 inhibited cell proliferation. C-82 led to an increase in the percentage of cells in the G0/G1 phase of the cell cycle. The percentage of cells in the sub-G1 phase also increased. Moreover, C-82 treatment significantly decreased the expression of cell proliferating markers and increased the expression of apoptosis-related proteins. Conclusion PRI-724(C-82) may be a novel drug for β-catenin-activated HCC therapy.

PURPOSE Recently, intrahepatic cholangiocarcinoma (iCCA) has been classified into small duct cholangiocarcinoma (SDC) and large duct cholangiocarcinoma (LDC) according to the origin of the biliary tree. Although the usefulness of F-FDG PET/CT in iCCA is well known, there are no reports evaluating differences in accumulation of F-FDG according to the recently described iCCA subtypes. The aim of this study was therefore to assess F-FDG accumulation and the expression of glucose transporters in SDC and LDC. METHODS Our institutional review board approved this retrospective study and waived the requirement for informed consent. Fourteen consecutive surgically resected mass-forming iCCA (7 SDCs, 23 ± 6.7 mm; 7 LDCs, 44 ± 26 mm) were enrolled. The SUVmax on F-FDG PET/CT and the expression of glucose transporter 1 (Glut-1), Glut-2, hexokinase 2 (HK2), and glucose-6-phosphatase by immunohistochemistry were evaluated and compared between SDC and LDC. RESULTS The SUVmax in SDC was significantly lower than that in LDC (3.2 ± 0.8 vs 7.6 ± 3.2, P < 0.01). The staining scores of Glut-1 and HK2 were significantly lower in SDC than in LDC (0 vs 3 ± 1.4, P = 0.0034; 1.6 ± 1.1 vs 3.4 ± 1.1, P = 0.014, respectively). Expression levels of Glut-2 and glucose-6-phosphatase were variable and did not show a significant difference between SDC and LDC. Overall survival was significantly worse in LDC than in SDC (P = 0.01). CONCLUSIONS F-FDG accumulation and Glut-1 and HK2 expression were significantly higher in LDC than in SDC. A low-glycolytic feature may be one of the characteristic findings of SDC.

The purpose of this study is to identify points useful in the imaging differentiation of hepatocellular carcinoma (HCC) showing hyperintensity on the hepatobiliary phase of gadoxetic acid-enhanced MRI and focal nodular hyperplasia (FNH) and FNH-like nodules.We enrolled consecutive 51 pathologically diagnosed HCCs that were hyperintense on hepatobiliary phase imaging (47 patients, including 44 with cirrhosis) and 10 FNHs and eight FNH-like nodules (16 patients, including five with cirrhosis). Imaging findings of dynamic CT and gadoxetic acid-enhanced MRI were assessed by two radiologists and compared between HCC and FNH.The apparent diffusion coefficient (ADC) was lower in hyperintense HCC than in FNH (p = 0.004). The enhancement patterns of hyperintense HCC and FNH at dynamic CT were significantly different (p0.0001), with 95.9% of HCCs and 22.2% of FNHs showing arterial phase enhancement with a washout pattern, and 4.1% of HCCs and 77.8% of FNHs showing arterial phase enhancement without a washout pattern. The frequency of coronalike enhancement was 84.3% in hyperintense HCCs versus 11.1% in FNHs (p0.0001). The signal distribution on the hepatobiliary phase was significantly different between hyperintense HCCs and FNHs (p = 0.0002). The frequency of a capsulelike rim was 88.2% versus 22.2%, that of a mosaic appearance was 72.5% versus 11.1%, and that of a central scar was 0% versus 55.6% in hyperintense HCCs versus FNHs (all p0.0001). Multivariate logistic regression analysis showed that ADC ratio (p = 0.03; odds ratio, 0.12) and enhancement pattern at dynamic CT (p = 0.04; odds ratio, 16.21) were the independent factors for differentiation between hyperintense HCC and FNH.For the diagnosis of hyperintense HCC differentiated from FNH and FNH-like nodule, arterial phase enhancement and washout pattern at dynamic CT and decrease of ADC ratio would be important findings.

Peribiliary glands are minute structures that are distributed along the intrahepatic large bile ducts, extrahepatic bile duct, and cystic duct. These glands regulate many physiological functions, such as enzyme secretion. Pancreatic exocrine tissues and enzymes are often observed in peribiliary glands; thus, peribiliary glands are involved in enzyme secretion. As such, these glands can be affected by conditions such as IgG4-related sclerosing cholangitis based on commonalities with their pancreatic counterparts. Cystic changes in peribiliary glands can occur de novo, as part of a congenital syndrome, or secondary to insults such as alcoholic cirrhosis. Biliary tree stem/progenitor cells have recently been identified in peribiliary glands. These cells are involved in turnover and regeneration of biliary epithelia as well as in sclerosing reactions in some pathological conditions, such as primary sclerosing cholangitis and hepatolithiasis. Notably, hepatolithiasis is involved in mucin secretion by the peribiliary glands. Additionally, these cells are associated with the manifestation of several neoplasms, including intraductal papillary neoplasm, cystic micropapillary neoplasm, and cholangiocarcinoma. Normal peribiliary glands themselves are particularly small structures that cannot be recognized using any available imaging modalities; however, these glands are closely associated with several diseases, as mentioned above, which have typical imaging features. Therefore, knowledge of the basic pathophysiology of peribiliary glands is helpful for understanding biliary diseases associated with the peribiliary glands.

Peri-tumoral hyperintensity (P-hyperintensity) is occasionally seen in hepatocellular carcinoma (HCC) on the hepatobiliary (HB) phase of gadoxetic acid-enhanced MRI (EOB-MRI). A recent study reported peri-tumoral hyperplasia (P-hyperplasia) associated with over-expression of glutamine synthetase (GS) in HCC or metastatic carcinoma. The aim of this study was to analyze the correlation between P-hyperintensity on the HB phase and GS expression indicating P-hyperplasia and reveal its pathological features. Seventy-seven surgically resected HCCs from 68 patients were analyzed. The grade of P-hyperintensity on HB phase was divided according to the degree of the peri-tumoral hyperintense signal: grade 0 (no P-hyperintensity), grade 1 (less than 50% of the tumor border), grade 2 (50%–80%), grade 3 (80%–100%). Immunohistochemical staining for GS and organic anion transporter polypeptides (OATP)1B3 was performed. The relationships among P-hyperplasia (peri-tumoral GS expression) and OATP1B3 expression, P-hyperintensity, and pathological features of the tumor were analyzed. Thirty-four HCCs were classified as P-hyperintensity grade 0, 29 HCCs as grade 1,10 nodules as grade 2, and 4 HCCs as grade 3. P-hyperplasia was observed in 3/34 (8.8%) P-hyperintensity grade 0, 16/29 (55.2%) grade 1, 9/10 (90%) grade 2, and 4/4 (100%) grade 3. The incidence of P-hyperplasia was significantly increased in P-hyperintensity grades 1–3 compared with grade 0 (p

Aim The aim of this study is to clarify the correlation of the co-activation of β-catenin and hepatocyte nuclear factor (HNF)4α with the findings of gadoxetic acid-enhanced magnetic resonance imaging (MRI), organic anion transporting polypeptide (OATP)1B3 expression, and histological findings in hepatocellular carcinoma (HCC). Methods One hundred and ninety-six HCCs surgically resected from 174 patients were enrolled in this study. The HCCs were classified into four groups by immunohistochemical expression of β-catenin, glutamine synthetase (GS), and HNF4α: (i) β-catenin/GS (positive [+]) HNF4α (+); (ii) β-catenin/GS (+) HNF4α (negative [−]); (iii) β-catenin/GS (−) HNF4α (+); and (iv) β-catenin/GS (−) HNF4α (−). We compared the four groups in terms of the enhancement ratio on the hepatobiliary phase of gadoxetic acid-enhanced MRI, immunohistochemical organic anion transporter polypeptide (OATP)1B3 (a main uptake transporter of gadoxetic acid) expression and histological features, overall survival, and no recurrence survival. The Kruskal–Wallis test, Steel–Dwass multiple comparisons test, Fisher's exact test, and log–rank (Mantel–Cox) test were used for statistical analyses. Results Enhancement ratio on gadoxetic acid-enhanced MRI in HCC with β-catenin/GS (+) HNF4α (+) was significantly higher than those of the other three groups (P

Purpose To identify biochemical factors associated with liver enhancement over time on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) images and predict the optimal time point of the hepatobiliary phase in various clinical settings. Materials and Methods This study was approved by the institutional review boards, and written informed consent was obtained from the 1903 patients enrolled. Simple and multiple logistic regression analyses were performed to investigate the biochemical factors associated with liver-to-spleen contrast (LSC) of at least 1.5 in the hepatobiliary phase. Changes in LSC and lesion-to-liver contrast (LLC) of lesions over time (at 5, 10, 15, and 20 minutes) were investigated with a linear mixed-effects model in patients and lesions. For LSC, the optimal cutoff value was determined with receiver operating characteristic analysis of the most significant variable. Differences in LSC and LLC were analyzed in various clinical settings. Results Ultimately, 1870 patients were evaluated, as 33 were excluded according to study criteria. Prothrombin (PT) activity, total bilirubin level (P = .020), and total cholesterol level (P = .005) were significantly associated with LSC of at least 1.5 at 20 minutes, and PT activity was identified as the most significant factor (odds ratio, 1.271; 95% confidence interval: 1.109, 1.455; P = .001). LSC of at least 1.5 at 20 minutes with PT activity of at least 86.9% and less than 86.9% occurred in 555 of 626 patients (88.6%) and 388 of 575 patients (67.5%), respectively. Satisfactory liver enhancement at 20 minutes was significantly more likely to be achieved by patients with hepatitis B virus than by those with hepatitis C virus (P < .001) and by patients with metastasis than by those with hepatocellular carcinoma (P < .001). No significant difference in LLC was observed in patients examined at 1.5 and 3.0 T (P = .133). Conclusion Hepatic enhancement is significantly associated with PT activity, total bilirubin level, and total cholesterol level. PT activity of at least 86.9% could be used to shorten examination times at Gd-EOB-DTPA-enhanced MR imaging. © RSNA, 2016 Online supplemental material is available for this article.

Gadoxetic acid-enhanced magnetic resonance imaging (MRI) plays important roles in diagnosis of hepatic lesions because of its superiority in the detectability of small lesions, its differentiation ability, and its utility for the early diagnosis of hepatocellular carcinoma (HCC). In HCC, expression of organic anion transporting polypeptide (OATP) 1B3 correlates with the enhancement ratio in the hepatobiliary phase. Gadoxetic acid-enhanced MRI, an indirect molecular imaging method, reflects OATP1B3 expression in HCC. OATP1B3 expression gradually decreases from the dysplastic nodule stage to advanced HCC. Decreased expression is a sensitive marker of multistep hepatocarcinogenesis, especially in the early stages. Hypervascular HCCs commonly show hypointensity in the hepatobiliary phase corresponding to a decrease in OATP1B3; however, approximately 10% of HCCs show hyperintensity due to OATP1B3 overexpression. This hyperintense HCC shows less aggressive biological features and has a better prognosis than hypointense HCC. Hyperintense HCC can be classified into a genetic subtype of HCC with a mature hepatocyte-like molecular expression. OATP1B3 expression and the less aggressive nature of hyperintense HCC are regulated by the molecular interaction of β-catenin signaling and hepatocyte nuclear factor 4α, a tumor suppressor factor. Gadoxetic acid-enhanced MR imaging has the potential to be an imaging biomarker for HCC. KEY POINTS: • The hepatobiliary phase is a sensitive indirect indicator of organic anion transporting polypeptide1B3 (OATP1B3) expression in hepatocellular carcinoma (HCC). • The OATP1B3 expression, namely, enhancement in the hepatobiliary phase, decreases from the very early stage of hepatocarcinogenesis, contributing to early diagnosis of HCC. • HCC showing hyperintensity on the hepatobiliary phase is a peculiar genetic subtype of HCC with OATP1B3 overexpression, a less aggressive nature, and mature hepatocyte-like molecular/genetic features.

OBJECTIVE. The objective of our study was to characterize the CT findings of IgG4-related paravertebral lesions. MATERIALS AND METHODS. We selected cases of IgG4-related paravertebral lesions that satisfied two inclusion criteria: first, lesions in patients with IgG4-related disease diagnosed by a multidisciplinary approach between April 2007 and June 2018; and, second, patients who had soft-tissue lesions in paravertebral regions on CT images. We added one case of an IgG4-related paravertebral lesion diagnosed pathologically in 2003. Finally, the study consisted of 30 patients (25 men and five women; median age, 69.5 years). We retrospectively evaluated the CT findings of the paravertebral lesions. RESULTS. A total of 31 paravertebral lesions were identified in 30 patients. All lesions were located around thoracic vertebrae, particularly the lower thoracic regions (n = 30). Twenty-six lesions (84%) involved two or more vertebrae in a row. The right side of vertebrae was predominantly affected in all cases except one (30/31 lesions). Radiologically, the paravertebral lesions were characterized as a bandlike, demarcated soft-tissue mass (mean maximum thickness, 8.7 mm) with homogeneous enhancement on late phase images of contrast-enhanced CT. All patients had IgG4-related lesions at other sites. Histologically, paravertebral lesions showed sclerosing inflammation consisting of diffuse lymphoplasmacytic infiltrations with many IgG4-positive plasma cells and irregular fibrosis. CONCLUSION. IgG4-related paravertebral lesions occur mainly in the right side of the lower thoracic vertebrae and present as a homogeneously enhanced bandlike mass corresponding to plasma cell-rich sclerosing inflammation.

Cholangiocarcinoma (CC) is a malignant tumor which arises from the biliary epithelium and most cases represent adenocarcinoma. CC can be classified into intrahepatic CC (ICC), perihilar CC, and distal CC, based on the site of anatomic origin. The incidence of ICC is increasing in both Western and Eastern countries, while that of extrahepatic cholangiocarcinoma remains fairly stable. ICC infiltrates into adjacent nerves and lymphatic vessels, resulting in progressive disease with a poor prognosis; thus, early detection of ICC is critical for achieving better outcomes and providing better patient care. However, it is difficult for clinicians to detect an ICC, especially in its early stage. Different from hepatocellular carcinoma, the lack of surveillance system for the high-risk group of CC does not allow for a reliable screening examination. In this context, for early detection and diagnosis of ICC, radiologists need to know predisposing conditions that can lead to the development of ICC, such as chronic biliary or hepatic inflammation, primary sclerosing cholangitis, congenital biliary diseases, and other conditions. In this article, we discuss and illustrate the radiologic features of ICC with special attention to early disease stages and of predisposing conditions of ICC.

To determine the imaging and clinicopathological features of MRI doughnut-like nodules (HBP-doughnut nodules), hyperintense at the hepatobiliary phase (HBP) after injection of gadoxetic acid (EOB) and without arterial-phase hyperenhancement (APHE) in cirrhotic liver. The Institutional Review Board approved this retrospective study and informed consent was waived. We enrolled 309 consecutive patients with liver cirrhosis who were examined by EOB-MRI, dynamic CT, and angiography-assisted CT between 2008 and 2012 and searched for HBP-doughnut nodules. We evaluated imaging characteristics including haemodynamics and signal intensity of MRI, pathological findings, and frequency of malignant transformation. One hundred and one HBP-doughnut nodules without APHE were identified in 18 patients (6%), including seven of 59 (12%) patients with hepatitis-B-virus-related, nine of 230 (3.9%) with hepatitis-C-virus-related, and two of 33 (6.1%) with alcoholic cirrhosis. All nodules showed enhancement peaks in the portal phase, the same or increased intranodular portal supply on CT during arterial portography, and the same or decreased intranodular arterial supply on CT during hepatic arteriography. On T2-weighted and diffusion-weighted images, 37 (36%) and 24 (24%) nodules, respectively, showed hyperintensity predominantly in the central area. Three nodules were diagnosed by fine needle biopsy as non-neoplastic hepatic nodules. Ninety-three of 101 (92%) nodules in 16 patients were followed up during an observation period of 1163 ± 902 days (range 57–2920 days), and none showed malignant transformation. HBP-doughnut nodules without APHE in cirrhotic liver were not infrequent. None became malignant. We propose calling them ‘multiacinar cirrhotic nodules’ based on the classification by an International Working Party. • HBP-doughnut nodules without APHE were seen in 6% of patients with liver cirrhosis. • The enhancement peak of HBP-doughnut nodules without APHE was in the portal phase, which reflected the fact that they were supplied predominantly by the portal vein, based on angiography-assisted CT findings. • None of the HBP-doughnut nodules without APHE in cirrhotic liver became malignant, and in conjunction with limited pathological features, they may be corresponding to multiacinar cirrhotic nodules in the International Working Party classification.

To reveal the relationship between abdominal movement and artifact, and to reveal if the transient artifact in arterial phase is caused by transient abdominal movement (TAM) in contrast-enhanced (CE) MRI. 325 CE-MRI series (206 with EOB and 119 with EGCM) were included. The abdominal movement was classified into three groups by respiratory bellows waveform (= bellows grade, BG 1–3), and MR image quality (= artifact score, AS) was graded 1–5 for the precontrast, arterial and portal venous phase, respectively. The relationship between the BG and AS was evaluated. The occurrence of transient artifact in arterial phase was compared to the degree of TAM. In the acquisitions with BG3, all images showed AS of > 2, while no images had AS of > 4 in the acquisitions with BG1. Numbers of transient artifact in the arterial phase with no-abdominal movement (NAM), mild-TAM, severe-TAM were 0 of 120, 4 of 27, 7 of 8 in EOB and 0 of 91, 1 of 4, 0 of 0 in EGCM, respectively. Image quality is highly correlated with abdominal movement. Moreover, artifact in arterial phase was not observed in NAM, which indicated abdominal movement is the direct cause of artifact.

To elucidate the dynamic CT features of pure type of cholangiolocellular carcinoma (pure CoCC) in comparison with those of cholangiocellular carcinoma (CCC) and to analyze their bases by angiography-assisted CT with histopathologic correlation. Surgically confirmed 10 pure CoCCs, 10 CCCs and 7 mixed CoCC and CCCs from August 2001 to May 2012 were included in this study. Among them, dynamic CT features were compared. In 8 pure CoCCs, the correlative study between angiography-assisted CT and histopathological study was performed to clarify the basic mechanism of dynamic CT features. All pure CoCCs showed early and prolonged enhancement homogeneously or inhomogeneously and 8 of 10 pure CoCCs showed early peritumoral enhancement on dynamic CT. Time-attenuation curve provided by dynamic CT showed significant higher Hounsfield unit value of pure CoCC than those of CCC at each phases (p

Background We analysed the haemodynamics of indocyanine green (ICG) in mouse organs and tumours and evaluated responses to anti-angiogenic agents in an allograft tumour mouse model by photoacoustic imaging. Methods Thirty-six male mice (aged 10–14 weeks; body weight 20–25 g) were used. Real-time photoacoustic imaging of organs and tumours after intravenous injection of ICG was conducted in mice until 10 min after ICG injection. ICG distribution in tumour tissues was assessed by immunohistochemical staining and observation of ICG-derived fluorescence. Vascular permeability changes induced by the vascular endothelial growth factor (VEGF)-blocking agent VEGF-trap on tumour photoacoustic signals were studied. Results The photoacoustic signals in salivary glands and tumours after intravenous injection of iCG (0.604 ± 0.011 and 0.994 ± 0.175 [mean ± standard deviation], respectively) were significantly increased compared with those in the liver, kidney, and great vessel (0.234 ± 0.043, 0.204 ± 0.058 and 0.127 ± 0.040, respectively; p

Purpose To evaluate the utility of photoacoustic imaging in measuring changes in renal oxygen saturation after ischemia-induced acute kidney injury, and to compare these measurements with histological findings and serum levels of kidney function. Material and Methods Acute kidney injury was induced by clamping the left renal pedicle in C57Bl/6 mice, with a 35-min ischemic period used to induce mild renal injury (14 mice) and a 50-min period for severe injury (13 mice). The oxygen saturation was measured before induction, and at 5 time-points over the first 48 h after induction, starting at 4 h after induction. Oxygen saturation, histological score, kidney volume, and the 24 h creatinine clearance rate and serum blood urea nitrogen were also measured on day 28. Between-group differences were evaluated using a Mann-Whitney U-test and Dunn’s multiple comparisons. The association between oxygen saturation and measured variables was evaluated using Spearman’s correlation. A receiver operator characteristic curve was constructed from oxygen saturation values at 24 h after heminephrectomy to predict chronic renal function. Results The oxygen saturation was higher in the mild than severe renal injury group at 24 h after induction (73.7% and 66.9%, respectively, P

We report a female case of sinusoidal obstruction syndrome (SOS) diagnosed pathologically after chemotherapy (Pmab+m-FOLFOX6) for ascending colon cancer with multiple liver metastases, focusing on the findings of gadoxetic acid-enhanced MRI (EOB-MRI) and the organic anion transporting polypeptide 1B3 (OATP1B3) expression of in the liver. The patient was a 75-year-old female. She had received chemotherapy (Pmab+m-FOLFOX6) as six cycles for preoperative chemotherapy. After the preoperative chemotherapy, tumor sizes of hepatic metastases were reduced and hepatobiliary phase of EOB-MRI clearly depicted diffuse reticular hypointensity in the background liver. On the other hand, dynamic CT and/or other sequences of EOB-MRI did not show definite abnormality in the background liver. After the operation, this patient was pathologically confirmed as SOS demonstrating centrilobular congestion, sinusoidal dilatation, and perisinusoidal fibrosis. In normal liver parenchyma, OATP1B3 (uptake transporter of the EOB-MRI) expression is observed predominantly in centrilobular hepatocytes (zone 3). On the other hand, OATP1B3 expression was remarkably reduced because of the damages in the centrilobular (zone 3) hepatocytes in this SOS case. This indicated that EOB-MRI might be extremely sensitive in diagnosing SOS in its early stage.

Recent advances in highly conformal radiotherapies greatly extend the indications for radiotherapy of liver tumors. However, because of poor tolerance to hepatic radiation, estimation of the intensity of irradiation of the liver is important, particularly for a cirrhotic liver. Knowledge of radiation-induced hepatitis is important for understanding how to optimize hepatic radiation therapy. Pathological changes of the irradiated liver, which include perivenular fibrosis, sinusoidal obstruction, and damage to Kupffer cells and hepatocytes, can be visualized using clinical imaging techniques. This review article discusses and illustrates the pathological and radiological changes of hepatic tumors and the surrounding parenchyma of the irradiated liver.

The aim of this study is to clarify the correlation of the co-activation of β-catenin and hepatocyte nuclear factor (HNF)4α with the findings of gadoxetic acid-enhanced magnetic resonance imaging (MRI), organic anion transporting polypeptide (OATP)1B3 expression, and histological findings in hepatocellular carcinoma (HCC).One hundred and ninety-six HCCs surgically resected from 174 patients were enrolled in this study. The HCCs were classified into four groups by immunohistochemical expression of β-catenin, glutamine synthetase (GS), and HNF4α: (i) β-catenin/GS (positive [+]) HNF4α (+); (ii) β-catenin/GS (+) HNF4α (negative [-]); (iii) β-catenin/GS (-) HNF4α (+); and (iv) β-catenin/GS (-) HNF4α (-). We compared the four groups in terms of the enhancement ratio on the hepatobiliary phase of gadoxetic acid-enhanced MRI, immunohistochemical organic anion transporter polypeptide (OATP)1B3 (a main uptake transporter of gadoxetic acid) expression and histological features, overall survival, and no recurrence survival. The Kruskal-Wallis test, Steel-Dwass multiple comparisons test, Fisher's exact test, and log-rank (Mantel-Cox) test were used for statistical analyses.Enhancement ratio on gadoxetic acid-enhanced MRI in HCC with β-catenin/GS (+) HNF4α (+) was significantly higher than those of the other three groups (P 0.001). The OATP1B3 grade was also significantly higher in HCC with β-catenin/GS (+) HNF4α (+) (P 0.001). Hepatocellular carcinoma with β-catenin/GS (+) HNF4α (+) showed the highest differentiation grade as compared to the other groups (P 0.004). There were no significant differences in portal vein invasion, macroscopic growth pattern, or prognosis analyses between the four groups.Co-activation of β-catenin and HNF4α would promote OATP1B3 expression, and consequently higher enhancement ratio on gadoxetic acid-enhanced MRI and higher differentiation grade in HCC.

The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha-fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd-EOB-DTPA uptake in the hepatobiliary phase was observed in ∼15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd-EOB-DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd-EOB-DTPA uptake in vivo. HCC classification based on EOB-MRI and serum AFP levels predicted overall survival in a single-institution cohort (n = 70), and its prognostic utility was validated independently in a multi-institution cohort of early-stage HCCs (n = 109). Conclusion: This noninvasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease. (Hepatology 2014;60:1674–1685)

We evaluated molecular features of hypervascular hepatocellular carcinoma (HCC) that shows iso- or hyperintensity (hyperintense HCC) in the hepatobiliary phase (HB phase) of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI). We investigated 89 surgically resected cases. Patients were divided into two groups according to the signal intensity in the HB phase of EOB-MRI: hyperintense HCCs (n = 18) and hypointense HCCs (n = 71). We performed immunohistochemical staining for uptake transporter of gadoxetic acid: organic anion transporter polypeptides (OATP8); tumor markers: alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II); hepatic stem cell markers: epithelial cell adhesion molecule (EpCAM), cytokeratin 19 (CK19), and neural cell adhesion molecule (NCAM); biliary marker: CK7; hepatocyte marker: hepatocyte paraffin 1 (HepPar1); markers of HCC differentiation: glypican-3; signaling: beta-catenin, and the respective grade was semiquantitatively determined. Histopathologically, hyperintense HCCs showed significantly weaker expression of AFP (p

To analyze the correlation among biologic features, tumor marker production, and signal intensity at gadoxetic acid-enhanced MR imaging in hepatocellular carcinomas (HCCs).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.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).The results suggest that hyperintense HCCs on gadoxetic acid-enhanced MR images are less aggressive than hypointense HCCs.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120226/-/DC1.

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.

Background Indocyanine green (ICG) excretory defect is a dye excretory disorder, and it is characterized by the selective impairment of plasma ICG clearance with normal liver histology. The pathophysiology involves selective loss of active transporters for ICG in the hepatic cell membrane. Several cases of hepatectomy in patients with ICG excretory defect have been reported, but the expression of hepatic transporters involved in ICG excretory defect has not been examined in these cases. Case presentation An 81-year-old man who was hepatitis B and C virus negative was admitted to our hospital with a diagnosis of HCC. Abdominal computed tomography revealed an 8-cm-diameter tumor in hepatic segments 4 and 8. The retention rate of ICG at 15 min (ICGR15), which has been used to evaluate hepatic functional reserve, was markedly elevated (79.1 %), whereas other liver function test results, were normal. Therefore, we diagnosed the patient with HCC with an ICG excretory defect, and considered major hepatectomy. Central bisectionectomy was performed, and the postoperative course was uneventful. Microscopic examination of the resected specimen showed moderately differentiated HCC. Immunohistochemical staining and polymerase chain reaction analysis of a non-neoplastic site of the resected specimen showed very few expression of the organic anion-transporting polypeptide 1B3 (OATP1B3), which is usually expressed on the basolateral membrane of human hepatocytes and mediates the uptake of ICG. Conclusions In this case, we present a case of hepatectomy for HCC in a patient with ICG excretory defect, which may be attributable to a congenital disorder of OATP1B3 expression; however, an ICG excretory defect did not seem to have any effect on the short-term prognosis after hepatectomy.

To evaluate the morphometric changes in liver cirrhosis using multidetector CT volumetry and to analyse the differences in morphometric changes among different aetiologies and stages of cirrhosis.Each portal segment with the respective proportion relative to total liver volume was measured in 54 patients without cirrhosis as a control (male/female, 29/25; 62.4 ± 7.6 years) and 250 patients with cirrhosis (male/female, 172/78; 64.6 ± 9.2 years) related to hepatitis virus infection (n = 96), alcoholism (n = 88) and non-alcoholic steatohepatitis (NASH) (n = 66). 149 patients were classified as patients with Child-Pugh Class A, 57 patients as patients with Class B and 44 patients as patients with Class C. The Kruskal-Wallis test was used for statistical analysis (p 0.05).Cirrhosis associated with all aetiologies commonly showed atrophy of the medial and anterior segments and right lobe and hypertrophy of the lateral segment and caudate lobe compared with the control (p 0.05). In Child-Pugh Class A, hypertrophy of the caudate lobe progressed more in alcoholism and NASH than in virus-related aetiologies (p 0.001). Hypertrophy of the lateral segment and atrophy of the medial and anterior segments and right lobe progressed less in NASH than in cases with virus related and alcoholic cirrhosis (p 0.001). In patients with Class B, these differences were less prominent than in those with Class A (p 0.001). In Class C, no significant differences were noted in any segment, regardless of aetiology (p 0.05).Morphometric changes of cirrhosis display different patterns according to aetiology. Differences between aetiologies would decrease with progression of cirrhosis.Morphometric changes of cirrhosis display different patterns according to aetiology. Differences between aetiologies would decrease with progression of cirrhosis.

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.

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).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.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).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.

To clarify the changes that occur in drainage vessels of dysplastic nodules and hepatocellular carcinoma (HCC) during hepatocarcinogenesis by using computed tomography (CT) during arterial portography (CTAP) and CT during hepatic arteriography (CTHA), with histologic findings as the reference standard.Institutional ethics committee approval and informed consent were obtained. According to the findings at CTAP and CTHA, 46 surgically resected hepatocellular nodules were classified into three types: type A (n = 18) (equivalent or decreased portal perfusion compared with background liver at CTAP, decreased arterial perfusion, and no corona enhancement [perinodular contrast material drainage] at CTHA), type B (n = 13) (no portal perfusion, increased arterial perfusion, and thin (or = 2-mm) corona enhancement), or type C (n = 15) (no portal perfusion, increased arterial perfusion, and thick (2-mm) corona enhancement). We compared the histopathologic features and microangioarchitecture between the types.Type A nodules histologically consisted of dysplastic nodules and well-differentiated HCC; type B and C nodules were moderately differentiated HCC. Replacing growth was commonly observed in type A nodules, whereas compressing growth was more frequently seen in types B and C. Sixty percent of type C nodules had a fibrous capsule. There were significantly fewer intranodular hepatic veins in types B and C. Serial pathologic slices demonstrated continuity from intranodular capillarized sinusoids to hepatic veins in type A nodules and to surrounding hepatic sinusoids in type B nodules. In type C nodules, intranodular capillarized sinusoids were connected to extranodular portal veins either directly or through portal venules within the fibrous capsule.Drainage vessels of HCC change from hepatic veins to hepatic sinusoids and then to portal veins during multistep hepatocarcinogenesis.