Reactive lymphoid hyperplasia of the liver: A case report featuring characteristic nodular and perinodular enhancement.

A 53-year-old female with primary biliary cholangitis was referred for the evaluation of a hepatic nodule identified during routine imaging. Ultrasonography revealed a homogeneous, hypoechoic, 18 mm nodule in segment 3 of the liver. On dynamic CT and MRI, the nodule showed mild enhancement at the hepatic artery-dominant phase. On diffusion-weighted images, the nodule exhibited pronounced hyperintensity with accompanying wedge-shaped perinodular hyperintensity (comet and comet-tail appearance). The nodule showed a portal perfusion defect on CT during arterial portography, and mild enhancement on CT during hepatic arteriography (CTHA). A nodular and wedge-shaped perinodular enhancement (comet and comet-tail appearance) in the CTHA was also clearly observed. The nodule demonstrated abnormal FDG uptake on 18F-FDG-PET/CT. An excisional biopsy was performed for histopathological diagnosis, and the nodule was diagnosed as reactive lymphoid hyperplasia (RLH). Diagnosing hepatic RLH by imaging is challenging due to its imaging findings overlapping with those of various malignant tumors, especially the nodular type of lymphomas, making differentiation particularly difficult. However, radiologists should note the perinodular early enhancement and the perinodular hyperintensity on diffusion weighted images, which are thought to be key imaging findings of RLH, along with other characteristics such as a single, small, homogeneous nodule with mild early enhancement and marked restricted diffusion. We propose to name the nodular lesion with perinodular early enhancement/hyperintensity on diffusion weighted images as 'comet and comet-tail appearances'.

Imaged periductal infiltration: Diagnostic and prognostic role in intrahepatic mass-forming cholangiocarcinoma.

Purpose: This study examines periductal infiltration in intrahepatic mass-forming cholangiocarcinoma (IMCC), focusing on its importance for differentiating hepatic tumors and its influence on post-surgical survival in IMCC patients. Methods: Eighty-three consecutive patients with IMCC (n = 43) and liver cancer whose preoperative images showed intrahepatic bile duct dilatation adjacent to the tumor for differential diagnosis from hepatocellular carcinoma (HCC) [n = 21], metastatic liver cancer (MLC) [n = 16] and combined hepatocellular-cholangiocarcinoma (cHCC-CC) [n = 3] were enrolled. CT and MRI findings of simple bile duct compression, imaged periductal infiltration, and imaged intrabiliary growth adjacent to the main tumor were reviewed. Clinicopathological and imaging features were compared in each group. The sensitivity, specificity, and odds ratio were calculated for each imaging finding of IMCC versus the other tumor groups. Overall survival was compared between cases of IMCC with and without imaged periductal infiltration. Results: Simple bile duct compression and imaged intrabiliary growth were more frequently observed in HCC than in the others (p < 0.0001 and 0.040, respectively). Imaged periductal infiltration was observed more often in histopathologically confirmed large-duct type IMCC than in the small-duct type IMCC (p = 0.034). Multivariable analysis demonstrated that only imaged periductal infiltration (odds ratio, 50.67) was independently correlated with IMCC. Patients with IMCC who had imaged periductal infiltration experienced a poorer prognosis than those without imaged periductal infiltration (p = 0.0034). Conclusion: Imaged periductal infiltration may serve as a significant marker for differentiating IMCC from other liver cancers. It may also have the potential to predict post-surgical outcomes in patients with IMCC.

Fat fraction and R2 * values of various liver masses: Initial experience with 6-point Dixon method on a 3T MRI system.

Purpose: To assess the feasibility of the 6-point Dixon method for evaluating liver masses. We also report our initial experience with the quantitative values in various liver masses on a 3T system. Materials and methods: Of 251 consecutive patients for whom 6-point Dixon was employed in abdominal magnetic resonance imaging scans between October 2020 and October 2021, 117 nodules in 117 patients with a mass diameter of more than 1 cm were included in the study. Images for measuring the proton density fat fraction (PDFF) and R2 * values were obtained using the iterative decomposition of water and fat with echo asymmetry and least-squares estimation-quantitative technique for liver imaging. Two radiologists independently measured PDFF (%) and R2 * (Hz). Inter-reader agreement and the differences between readers were examined using intra-class correlation coefficient (ICC) and the Bland-Altman method, respectively. PDFF and R2 * values in differentiating liver masses were examined. Results: The masses included hepatocellular carcinoma (n = 59), cyst (n = 20), metastasis (n = 14), hemangioma (n = 8), and others (n = 16). The ICCs for the region of interest (mm2), PDFF, and R2 * were 0.988 (95 % confidence interval (CI): 0.983, 0.992), 0.964 (95 % CI: 0.949, 0.975), and 0.962 (95 % CI: 0.941, 0.975), respectively. The differences of measurements between the readers showed that 5.1 % (6/117) and 6.0% (7/117) for PDFF and R2 * , respectively, were outside the 95 % CI. Conclusion: Our observation indicates that the 6-point Dixon method is applicable to liver masses.

Radiation dose considerations in digital radiography with an anti-scatter grid: A study using adult and pediatric phantoms.

BACKGROUND: When using an anti-scatter grid, a decrease in receptor dose caused by its X-ray absorption seems to lead to the misperception that radiation dose needs to be increased even in digital radiography (DR). OBJECTIVE: To demonstrate that there is no need to increase radiation dose in DR with a grid, based on a visual evaluation using an adult and a pediatric abdomen phantom (PAD and PPD , respectively). MATERIALS AND METHODS: Phantom images with and without a grid were obtained with exposure parameters determined based on a preliminarily measured signal-to-noise ratio improvement factor (SIF), an index for potential dose reduction when using a grid. In visual evaluation, four radiologists compared phantom images with a grid applied at different dose reduction rates (0% [no reduction], 18%, 36%, and 59% for PAD and 0% and 11% for PPD ) against an image without a grid at the baseline dose (as the reference). They graded the overall image quality of the former relative to that of the latter (reference) on a 3-point scale (3 = better, 2 = almost equal, 1 = worse). RESULTS: The mean scores for dose reduction rates of 0%, 18%, 36%, and 59% were 3.00, 3.00, 2.75, and 1.00, respectively, for PAD ; those for 0% and 11% were 2.13 and 1.63, respectively, for PPD . These results support the validity of our view that no dose increase is necessary when using an anti-scatter grid. Actually, there is even a potential for improvement in image quality with dose reduction rates of ≤36% for PAD . CONCLUSION: It is worth reconsidering the necessity of increasing radiation dose in the DR imaging of the adult and pediatric abdomens with an anti-scatter grid.

Universal Liver Imaging Lexicon: Imaging Atlas for Research and Clinical Practice.

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. Work of the U.S. Government published under an exclusive license with the RSNA. Online supplemental material is available for this article.

Dynamic CT and Gadoxetic Acid-enhanced MRI Characteristics of P53-mutated Hepatocellular Carcinoma.

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, χ2 test, multivariable regression analysis, receiver operating characteristic analysis, Kaplan-Meier method, and log-rank test. Immunohistochemical expression of P53, organic anion transporting polypeptide 1B3 (OATP1B3), and CD34 were evaluated, and the correlations were analyzed using the Pearson correlation test. Results In total, 149 patients (mean age, 67 years ± 9 [SD]; 103 men) with 173 HCCs were evaluated. P53-mutated HCC (n = 28) demonstrated higher serum α-fetoprotein (median, 127.5 ng/mL vs 5.5 ng/mL; P < .001), larger size (40.4 mm ± 29.7 vs 26.4 mm ± 20.5; P = .001), and higher rates of poorly differentiated HCC (22 of 28 [79%] vs 24 of 145 [17%]; P < .001). Dilated vasculature in the arterial phase of dynamic CT (odds ratio, 14; 95% CI: 3, 80; P = .002) and a lower relative enhancement ratio in the hepatobiliary phase (odds ratio, 0.05; 95% CI: 0.01, 0.34; cutoff value, 0.69; P = .002) independently predicted P53-mutated HCC. OATP1B3 expression and P53 expression were inversely correlated (P = .002; R = -0.24). Five-year overall survival was worse for P53-mutated HCC (50.0% vs 72.6%; P = .02). Conclusion Dilated vasculature at the arterial phase of dynamic CT and a lower relative enhancement ratio at the hepatobiliary phase of gadoxetic acid-enhanced MRI were useful markers for P53-mutated hepatocellular carcinoma with poor prognosis. © RSNA, 2022 Online supplemental material is available for this article.

A case of intrahepatic cholangiocarcinoma arising from a simple hepatic cyst via dysplasia and carcinomatous transformation.

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.

A low albumin level as a risk factor for transient severe motion artifact induced by gadoxetate disodium administration: A retrospective observational study with free-breathing dynamic MRI and an experimental study in rats.

OBJECTIVES: In the arterial phase of gadoxetate disodium administration for dynamic MRI, transient severe motion (TSM) sometimes occurs, making image evaluation difficult. This study was to identify risk factors for TSM in a clinical study, and confirm them and investigate the cause in an animal study. METHODS: A retrospective, single-center, observational study included patients who underwent dynamic MRI using gadoxetate disodium for the first time from April 2016 to September 2019 and free-breathing MRI was performed. Differences in clinical characteristics and laboratory tests between the presence and absence of TSM were examined. Animal experiments were conducted in 50 rats; gadoxetate disodium was injected into three sites (distal inferior vena cava (IVC), ascending aorta, and descending aorta) to identify the organ which triggers respiratory irregularities. Phosphate-buffered saline and gadopentetate dimeglumine were also injected into the distal IVC. In addition, to evaluate the effect of albumin, gadoxetate disodium was diluted with phosphate-buffered saline or 5% human serum albumin and injected into the ascending aorta. The time course of the respiratory rate was monitored and evaluated. RESULTS: 20 of 51 (39.2%) patients showed TSM. On multivariable analysis, a low albumin level was an independent risk factor (P = .035). Gadoxetate disodium administration caused significant tachypnea compared to gadopentetate dimeglumine or PBS (an elevation of 16.6 vs 3.0 or 4.3 breaths/min; both P < .001) in rats. The starting time of tachypnea was earlier with injection into the ascending aorta than into the descending aorta (10.3 vs 17.9 sec; P < .001) and the distal IVC (vs 15.6 sec; P < .001). With dilution with albumin instead of phosphate-buffered saline, tachypnea was delayed and suppressed (9.9 vs 13.0 sec; P < .001, 24.1 vs 17.0 breaths/min; P = .031). CONCLUSIONS: A low albumin level is a risk factor for TSM, which could be caused by the effect of gadoxetate disodium on the head and neck region.

Transcatheter arterial embolization of iatrogenic massive arterioportal fistula in the liver.

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.

Ultrasonography of IgG4-related dacryoadenitis and sialadenitis: Imaging features and clinical usefulness.

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.

Pathologic, Molecular, and Prognostic Radiologic Features of Hepatocellular Carcinoma.

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. An invited commentary by Bashir is available online. Online supplemental material is available for this article. ©RSNA, 2021.

Serum Laminin γ2 Monomer as a Diagnostic and Predictive Biomarker for Hepatocellular Carcinoma.

BACKGROUNDS AND AIMS: Structural dynamics of basement membrane components are still to be elucidated in the process of hepatocarcinogenesis. We evaluated the characteristics of HCC expressing laminin γ2 monomer (LG2m), a basement membrane component not detected in normal tissues, for HCC diagnosis. We further determined whether 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 (AFP)-negative, CD90-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 AFP. Serum LG2m was assessed in 24 healthy donors, 133 chronic liver disease patients, and 142 HCC patients, and sensitivity and specificity of LG2m testing for HCC diagnosis were 62.9% and 70.5%, respectively (cutoff, 30 pg/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, 60 pg/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 < 0.0001). CONCLUSIONS: LG2m is a predictive biomarker for the development of metastatic HCC. Elevated serum LG2m is an HCC risk in CHC patients who have achieved SVR.

Clinical features and diagnostic imaging of cholangiolocellular carcinoma compared with other primary liver cancers: a surgical perspective.

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.

Anti-tumor Activity of the Small Molecule Inhibitor PRI-724 Against ß-Catenin-activated Hepatocellular Carcinoma.

BACKGROUND/AIM: CBP is a transcriptional coactivator in the Wnt/ß-catenin pathway that is related to cell kinetics and differentiation. This study aimed to characterize ß-catenin-activated hepatocellular carcinoma (HCC) and evaluate the direct effects of PRI-724 (a selective inhibitor of Wnt/ß-catenin/CBP signaling) on HCC. MATERIALS AND METHODS: Immunohistochemistry for ß-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 ß-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 ß-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 ß-catenin-activated HCC therapy.

Direct-Acting Antiviral Agents Reduce the Risk of Malignant Transformation of Hepatobiliary Phase-Hypointense Nodule without Arterial Phase Hyperenhancement to Hepatocellular Carcinoma on Gd-EOB-DPTA-Enhanced Imaging in the Hepatitis C Virus-Infected Liver.

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.

Differences in 18F-FDG Uptake and Expression of Glucose Transporter Between 2 Distinct Subtypes of Mass-Forming Intrahepatic Cholangiocarcinomas.

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.

Impaired lesion detectability on gadoxetic acid-enhanced MR imaging in indocyanine green excretory defect: case series of three patients.

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.

Gadoxetic acid-enhanced MR imaging for hepatocellular carcinoma: molecular and genetic background.

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 ß-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.