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.

Ethiodized oil as an imaging biomarker after conventional transarterial chemoembolization.

Conventional transarterial chemoembolization (cTACE) utilizing ethiodized oil as a chemotherapy carrier has become a standard treatment for intermediate-stage hepatocellular carcinoma (HCC) and has been adopted as a bridging and downstaging therapy for liver transplantation. Water-in-oil emulsion made up of ethiodized oil and chemotherapy solution is retained in tumor vasculature resulting in high tissue drug concentration and low systemic chemotherapy doses. The density and distribution pattern of ethiodized oil within the tumor on post-treatment imaging are predictive of the extent of tumor necrosis and duration of response to treatment. This review describes the multiple roles of ethiodized oil, particularly in its role as a biomarker of tumor response to cTACE. CLINICAL RELEVANCE: With the increasing complexity of locoregional therapy options, including the use of combination therapies, treatment response assessment has become challenging; Ethiodized oil deposition patterns can serve as an imaging biomarker for the prediction of treatment response, and perhaps predict post-treatment prognosis. KEY POINTS: • Treatment response assessment after locoregional therapy to hepatocellular carcinoma is fraught with multiple challenges given the varied post-treatment imaging appearance. • Ethiodized oil is unique in that its' radiopacity can serve as an imaging biomarker to help predict treatment response. • The pattern of deposition of ethiodozed oil has served as a mechanism to detect portions of tumor that are undertreated and can serve as an adjunct to enhancement in order to improve management in patients treated with intraarterial embolization with ethiodized oil.

Hepatocellular adenomas: Understanding the pathomolecular lexicon, MRI features, terminology, and pitfalls to inform a standardized approach.

Hepatocellular adenomas (HCAs) are benign hepatic tumors that can be complicated by bleeding and/or malignant transformation. The epidemiology of HCAs has changed over recent decades, primarily influenced by an increased incidence of obesity in both men and women. Currently, at least eight distinct pathomolecular subtypes of HCAs have been identified, several of which have distinguishing and pertinent imaging features on MRI. Emerging evidence suggests that hepatobiliary phase appearance may provide diagnostic and prognostic information. The purpose of this article is to review the current pathomolecular lexicon and imaging features with emphasis on hepatobiliary phase appearance. Level of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1630-1640.

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.

Doughnut-like hyperintense nodules on hepatobiliary phase without arterial-phase hyperenhancement in cirrhotic liver: imaging and clinicopathological features.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. KEY POINTS: • 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.

Isolated Arteries Originating from the Intrahepatic Arteries: Anatomy, Function, and Importance in Intervention.

Isolated hepatic arteries are defined as hepatic terminal arterioles that are not accompanied by portal venules or bile ductules and penetrate the liver parenchyma and distribute to the hepatic capsule and intrahepatic hepatic veins. Abundant communications exist between intra- and extrahepatic arteries through isolated arteries and capsular arterial plexus. They play a principal role in the development of subcapsular hemorrhage and arterial collateral formation following transcatheter arterial chemoembolization for liver cancers. The anatomy, function, and clinical importance of isolated hepatic arteries in interventional radiology, especially regarding subcapsular hemorrhage and arterial collateral formation, are highlighted in this article.

Differentiation Between Hepatocellular Carcinoma Showing Hyperintensity on the Hepatobiliary Phase of Gadoxetic Acid-Enhanced MRI and Focal Nodular Hyperplasia by CT and MRI.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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 (p < 0.0001), 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 (p < 0.0001). 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 p < 0.0001). 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. CONCLUSION: 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.

Gadoxetic acid-enhanced magnetic resonance imaging reflects co-activation of ß-catenin and hepatocyte nuclear factor 4α in hepatocellular carcinoma.

AIM: The aim of this study is to clarify the correlation of the co-activation of ß-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 ß-catenin, glutamine synthetase (GS), and HNF4α: (i) ß-catenin/GS (positive [+]) HNF4α (+); (ii) ß-catenin/GS (+) HNF4α (negative [-]); (iii) ß-catenin/GS (-) HNF4α (+); and (iv) ß-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 ß-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 ß-catenin/GS (+) HNF4α (+) (P < 0.001). Hepatocellular carcinoma with ß-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. CONCLUSION: Co-activation of ß-catenin and HNF4α would promote OATP1B3 expression, and consequently higher enhancement ratio on gadoxetic acid-enhanced MRI and higher differentiation grade in HCC.

Accuracy of CT Colonography for Detection of Polypoid and Nonpolypoid Neoplasia by Gastroenterologists and Radiologists: A Nationwide Multicenter Study in Japan.

OBJECTIVES: The objective of this study was to assess prospectively the diagnostic accuracy of computer-assisted computed tomographic colonography (CTC) in the detection of polypoid (pedunculated or sessile) and nonpolypoid neoplasms and compare the accuracy between gastroenterologists and radiologists. METHODS: This nationwide multicenter prospective controlled trial recruited 1,257 participants with average or high risk of colorectal cancer at 14 Japanese institutions. Participants had CTC and colonoscopy on the same day. CTC images were interpreted independently by trained gastroenterologists and radiologists. The main outcome was the accuracy of CTC in the detection of neoplasms ≥6 mm in diameter, with colonoscopy results as the reference standard. Detection sensitivities of polypoid vs. nonpolypoid lesions were also evaluated. RESULTS: Of the 1,257 participants, 1,177 were included in the final analysis: 42 (3.6%) were at average risk of colorectal cancer, 456 (38.7%) were at elevated risk, and 679 (57.7%) had recent positive immunochemical fecal occult blood tests. The overall per-participant sensitivity, specificity, and positive and negative predictive values for neoplasms ≥6 mm in diameter were 0.90, 0.93, 0.83, and 0.96, respectively, among gastroenterologists and 0.86, 0.90, 0.76, and 0.95 among radiologists (P<0.05 for gastroenterologists vs. radiologists). The sensitivity and specificity for neoplasms ≥10 mm in diameter were 0.93 and 0.99 among gastroenterologists and 0.91 and 0.98 among radiologists (not significant for gastroenterologists vs. radiologists). The CTC interpretation time by radiologists was shorter than that by gastroenterologists (9.97 vs. 15.8 min, P<0.05). Sensitivities for pedunculated and sessile lesions exceeded those for flat elevated lesions ≥10 mm in diameter in both groups (gastroenterologists 0.95, 0.92, and 0.68; radiologists: 0.94, 0.87, and 0.61; P<0.05 for polypoid vs. nonpolypoid), although not significant (P>0.05) for gastroenterologists vs. radiologists. CONCLUSIONS: CTC interpretation by gastroenterologists and radiologists was accurate for detection of polypoid neoplasms, but less so for nonpolypoid neoplasms. Gastroenterologists had a higher accuracy in the detection of neoplasms ≥6 mm than did radiologists, although their interpretation time was longer than that of radiologists.

Long-term predictive factors of the morphology based outcome in bare platinum coiled intracranial aneurysms: Evaluation by pre- and post-contrast 3D time-of-flight MR angiography.

PURPOSE: Our aim was to identify long-term predictive factors of the morphology-based outcome (MBO) of bare platinum coiled intracranial aneurysms. MATERIALS AND METHODS: A retrospective analysis of 96 bare platinum coiled intracranial aneurysms followed up from 1997 to 2016 using pre- and post-contrast 3D time-of-flight MR angiography (MRA) was performed. Logistic regression analysis was used to identify factors associated with a positive history of surrounding coil mass enhancement (SCME) and poor MBO. Spearman's rank correlation test was used to analyze the relationship between the initial angiographic result (IAR) class, sequential change of the SCME category, and MBO grade. RESULTS: Factors independently associated with poor MBO were incomplete IAR (OR=14.94, 95%CI: 2.46, 289.21, P=0.002) and a history of SCME (OR=4.13, 95% CI: 1.05, 18.65, P=0.043). The MBO grade strongly correlated with the IAR class (correlation coefficient [r]=0.84, P<0.0001). MBO grade correlated with sequential change of the SCME category (r=0.56, P<0.0001). The sequential change of the SCME category correlated with IAR class (r=0.53, P<0.0001). CONCLUSION: Although IAR and its class were strong long-term predictive factors of MBO, a history of SCME and upgrading of sequential change of SCME category were also long-term predictive factors of the MBO of bare platinum coiled intracranial aneurysms.

Biochemical and Clinical Predictive Approach and Time Point Analysis of Hepatobiliary Phase Liver Enhancement on Gd-EOB-DTPA-enhanced MR Images: A Multicenter Study.

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.

Superselective Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma: Rationale, Technique, and Outcome.

Conventional transarterial chemoembolization with ethiodized oil and gelatin sponge (GS) particles is a standard technique for hepatocellular carcinoma. Ethiodized oil can temporarily block tumor sinusoids, portal venules, hepatic sinusoids, and arterial microcommunications. By adding GS embolization, strong ischemic effects not only on the tumor but also on the surrounding liver parenchyma can be achieved. Superselective conventional transarterial chemoembolization is mainly indicated for patients with Child-Pugh scores of 5-8, tumors ≤ 7 cm, and ≤ 5 lesions. According to a Japanese nationwide survey, the 5-year survival rate of patients with Child-Pugh class A and a single tumor was 52%.

"Biliary Diseases with Pancreatic Counterparts": Cross-sectional Imaging Findings.

On the basis of the similarities in the histopathologic findings and the clinical-biologic behaviors of select biliary and pancreatic conditions, a new disease concept, "biliary diseases with pancreatic counterparts," has been proposed. Both nonneoplastic and neoplastic pathologic conditions of the biliary tract have their counterparts in the pancreas. Immunoglobulin G4 (IgG4)-related sclerosing cholangitis is the biliary manifestation of IgG4-related sclerosing disease, and type 1 autoimmune pancreatitis is its pancreatic counterpart. People with chronic alcoholism can develop peribiliary cysts and fibrosis as well as pancreatic fibrosis and chronic pancreatitis simultaneously. Pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm are considered pancreatic counterparts for the biliary neoplasms of extrahepatic cholangiocarcinoma, intraductal papillary neoplasm of the biliary tract, and hepatic mucinous cystic neoplasm, respectively. The anatomic proximity of the biliary tract and the pancreas, the nearly simultaneous development of both organs from the endoderm of the foregut, and the presence of pancreatic exocrine acini within the peribiliary glands surrounding the extrahepatic bile ducts are suggested as causative factors for these similarities. Interestingly, these diseases show "nearly" identical findings at cross-sectional imaging, an observation that further supports this new disease concept. New information obtained with regard to biliary diseases can be used for evaluation of pancreatic abnormalities, and vice versa. In addition, combined genetic and molecular studies may be performed to develop novel therapeutic targets. For both biliary and pancreatic diseases, imaging plays a pivotal role in initial diagnosis, evaluation of treatment response, efficacy testing of novel drugs, and long-term surveillance.

Benign Hepatocellular Nodules: Hepatobiliary Phase of Gadoxetic Acid-enhanced MR Imaging Based on Molecular Background.

Gadoxetic acid is a contrast agent for magnetic resonance (MR) imaging with hepatocyte-specific properties and is becoming increasingly important in detection and characterization of hepatocellular carcinoma and benign hepatocellular nodules, including focal nodular hyperplasia (FNH), nodular regenerative hyperplasia (NRH), hepatocellular adenoma (HCA), and dysplastic nodule. In these hepatocellular nodules, a positive correlation between the grade of membranous uptake transporter organic anion-transporting polypeptide (OATP) 1B3 expression and signal intensity in the hepatobiliary (HB) phase has been verified. In addition, it has been clarified that OATP1B3 expression is regulated by activation of ß-catenin and/or hepatocyte nuclear factor 4α. On the other hand, recent studies have also revealed some of the background molecular mechanisms of benign hepatocellular nodules. FNH commonly shows iso- or hyperintensity in the HB phase with equal or stronger OATP1B3 expression, with map-like distribution of glutamine synthetase (a target of Wnt/ß-catenin signaling) and OATP1B3 expression. NRH shows doughnut-like enhancement with hypointensity in the central portion in the HB phase with OATP1B3 expression. The majority of HCAs show hypointensity in the HB phase, but ß-catenin-activated HCA exclusively demonstrates iso- or hyperintensity with increased expression of nuclear ß-catenin, glutamine synthetase, and OATP1B3. Dysplastic nodule commonly shows iso- or hyperintensity in the HB phase with similar to increased OATP1B3 expression, but one-third of high-grade dysplastic nodules can be demonstrated as a hypointense nodule with decreased OATP1B3 expression. Knowledge of these background molecular mechanisms of gadoxetic acid-enhanced MR imaging is important not only for precise imaging diagnosis but also understanding of the pathogenesis of benign hepatocellular nodules. ©RSNA, 2016.

Report of the 19th follow-up survey of primary liver cancer in Japan.

The 19th Nationwide Follow-up Survey of Primary Liver Cancer in Japan comprised 20 850 primary liver cancer patients newly registered at 482 medical institutions over a period of 2 years (from 1 January 2006 to 31 December 2007). Of these, 94.7% had hepatocellular carcinoma (HCC) and 4.4% had intrahepatic cholangiocarcinoma (ICC). In addition, follow-up data were obtained regarding 34 752 patients who were registered in the previous survey. Epidemiological and clinicopathological factors, diagnosis, and treatment were examined in newly registered patients. Compared with the 18th follow-up survey, the present follow-up survey suggested an increase in the number of elderly and female patients, a reduction in the number of hepatitis B surface antigen- and anti-hepatitis C virus antibody-positive patients, and a reduction in tumor size at the time of clinical diagnosis. In terms of local ablation therapy, the number of patients receiving radiofrequency ablation therapy increased. The cumulative survival rates for newly registered patients between 1996 and 2007 were calculated for each histological type (HCC, ICC, and combined HCC and ICC) and stratified according to background factors and treatments. The cumulative survival rates of newly registered patients between 1978 and 2007 were calculated after dividing individuals into groups according to registration date (1978-1987, 1988-1997, and 1998-2007). The data obtained from this follow-up survey will contribute to the medical management of primary liver cancer and facilitate future research.

[Emergency Thoracic Endovascular Aortic Repair of Ruptured Kommerell's Diverticulum with an Acute Aortic Dissection].

This case report describes emergency thoracic endovascular aortic repair (TEVAR) of a ruptured Kommerell's diverticulum associated with a type B acute aortic dissection in a patient with a right aortic arch. A 64-year-old male was admitted with symptoms of sudden paraplegia and shock. The computed tomography imaging showed right aortic arch anomaly, with mirror image branching of the major arteries. The aorta was dissected from the origin of the right subclavian artery to the terminal aorta, with a thrombosed false lumen. Rupture was found in a 6.3 cm aneurysm located in the distal arch, which was diagnosed as Kommerell's diverticulum. We performed emergency TEVAR, and the aneurysm was successfully excluded using deployment of a Gore Tag stent-graft. At 3 months' follow-up, the patient was doing well and showed shrinkage of the aneurysm was confirmed. TEVAR is considered to be a suitable procedure for an emergency aortic catastrophe even in patients with aortic anomaly.

A comparison of the surgical outcomes among patients with HBV-positive, HCV-positive, and non-B non-C hepatocellular carcinoma: a nationwide study of 11,950 patients.

OBJECTIVE: To compare the prognostic factors and outcomes after hepatic resection among patients with hepatitis B virus (HBV)-positive, hepatitis C virus (HCV)-positive, and negative for hepatitis B surface antigen and hepatitis C antibody, so-called "NBNC"-hepatocellular carcinoma (HCC) using the data from a nationwide survey. BACKGROUND: The incidence of NBNC-HCC is rapidly increasing in Japan. METHODS: A total of 11,950 patients with HBV-HCC (n = 2194), HCV-HCC (n = 7018), or NBNC-HCC (n = 2738) who underwent a curative hepatic resection were enrolled in this study. The clinicopathological features were compared among the groups. The significant prognostic variables determined by univariate analysis were subjected to a multivariate analysis using a Cox proportional hazard regression model. RESULTS: Liver function in the HCV-HCC group was significantly worse than that in the HBV-HCC and NBNC-HCC groups. The NBNC-HCC group had significantly more advanced HCC than the HCV-HCC group. The 5-year overall survival rates after hepatectomy in the HBV-HCC, HCV-HCC, and NBNC-HCC groups were 65%, 59%, and 68%, respectively. The 5-year recurrence-free survival (RFS) rates in these 3 groups were 41%, 31%, and 47%, respectively. Stratifying the RFS rates according to the TNM stage showed that the NBNC-HCC group had a significantly better prognosis than the HBV-HCC group in stages II, III, and IVA, and a significantly better prognosis than the HCV-HCC group in stages I and II. Multivariate analysis revealed a significantly better RFS rate in the NBNC-HCC group. CONCLUSIONS: The findings of this nationwide survey indicated that patients with NBNC-HCC had a significantly lower risk of HCC recurrence than those with HBV-HCC and HCV-HCC.

Hepatocellular Carcinoma with ß-Catenin Mutation: Imaging and Pathologic Characteristics.

PURPOSE: To identify the imaging features of hepatocellular carcinoma (HCC) associated with ß-catenin mutation and their relationship to pathologic findings. MATERIALS AND METHODS: Institutional ethics committee approval and informed consent were obtained. One hundred thirty-eight surgically resected HCCs were analyzed in this study. Immunohistochemical expression of ß-catenin and its transcriptional product, glutamine synthetase (GS), were graded and classified into three groups: the ß-catenin positive and GS positive group (HCC with ß-catenin mutation), the ß-catenin negative and GS positive group (intermediate HCC), and the ß-catenin negative and GS negative group (HCC without ß-catenin mutation). Clinical, pathologic, and imaging findings from dynamic computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance (MR) imaging (T1-weighted, T2-weighted, diffusion-weighted, and hepatobiliary phase imaging) were evaluated. Correlations among immunohistochemical expression of ß-catenin, GS, and organic anion transporting polypeptide 1B3 (uptake transporter of gadoxetic acid) were evaluated. The χ(2), Kruskal-Wallis, and Spearman correlation tests were used. RESULTS: HCCs with ß-catenin mutation (n = 27) showed a lower median contrast-to-noise ratio at diffusion-weighted imaging than did intermediate HCCs (n = 23) and HCCs without ß-catenin mutation (n = 84) (13.2, 24.4, and 27.0, respectively; P = .02), higher apparent diffusion coefficient (1.33, 1.13, and 1.12, respectively; P < .0001), higher contrast-to-noise ratio (0.58, -28.7, and -45.0, respectively; P < .0001) and higher enhancement ratio during the hepatobiliary phase (0.90, 0.50, and 0.42, respectively; P < .0001). At pathologic examination, HCCs with ß-catenin mutation showed pseudoglandular proliferation and bile production with a higher grade of differentiation (P = .04, .001, and .005, respectively). There were significant positive correlations among expression of ß-catenin, GS, and organic anion transporting polypeptide 1B3 (P < .0001). CONCLUSION: HCCs with ß-catenin mutation showed a higher grade of differentiation with frequent pseudoglandular patterns and bile production, and characteristic imaging findings included a high enhancement ratio at gadoxetic acid-enhanced MR imaging and a high apparent diffusion coefficient at diffusion-weighted imaging. Online supplemental material is available for this article.

Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.

UNLABELLED: 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.