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Purpose To evaluate the feasibility of liver MR fingerprinting (MRF) for quantitative characterization and diagnosis of focal liver lesions. Materials and Methods This single-site, prospective study included 89 participants (mean age, 62 years ± 15 [SD]; 45 women, 44 men) with various focal liver lesions who underwent MRI between October 2021 and August 2022. The participants underwent routine clinical MRI, non-contrast-enhanced liver MRF, and reference quantitative MRI with a 1.5-T MRI scanner. The bias and repeatability of the MRF measurements were assessed using linear regression, Bland-Altman plots, and coefficients of variation. The diagnostic capability of MRF-derived T1, T2, T2*, proton density fat fraction (PDFF), and a combination of these metrics to distinguish benign from malignant lesions was analyzed according to the area under the receiver operating characteristic curve (AUC). Results Liver MRF measurements showed moderate to high agreement with reference measurements (intraclass correlation = 0.94, 0.77, 0.45, and 0.61 for T1, T2, T2*, and PDFF, respectively), with underestimation of T2 values (mean bias in lesion = -0.5%, -29%, 5.8%, and -8.2% for T1, T2, T2*, and PDFF, respectively). The median coefficients of variation for repeatability of T1, T2, and T2* values were 2.5% (IQR, 3.6%), 3.1% (IQR, 5.6%), and 6.6% (IQR, 13.9%), respectively. After considering multicollinearity, a combination of MRF measurements showed a high diagnostic performance in differentiating benign from malignant lesions (AUC = 0.92 [95% CI: 0.86, 0.98]). Conclusion Liver MRF enabled the quantitative characterization of various focal liver lesions in a single breath-hold acquisition. Keywords: MR Imaging, Abdomen/GI, Liver, Imaging Sequences, Technical Aspects, Tissue Characterization, Technology Assessment, Diagnosis, Liver Lesions, MR Fingerprinting, Quantitative Characterization Supplemental material is available for this article. © RSNA, 2023.

Purpose: To assess the effect of an ultrahigh b value of 3000 s/mm 2 and the minimal TE of 53 ms on image quality and T2 shine-through effect in liver diffusion-weighted imaging (DWI) using a 3-Tesla MRI scanner with a peak gradient of 100 mT/m., Methods: At b values of 1000 and 3000 s/mm 2 and at the minimal (44-53 ms) and routine TEs (70 ms), DWI of our original phantom and liver DWI in 10 healthy volunteers and 26 patients with 35 hepatic hemangiomas were acquired with this scanner, and the quantified SNR of the phantom and the hepatic parenchyma in the volunteers and the contrast-to-noise ratio (CNR) of the hepatic hemangiomas were calculated; two independent readers qualitatively graded the overall image quality in the volunteers and determined the presence or absence of the T2 shine-through effect related to the hemangiomas in the patients. We compared the SNR and subjective overall image quality between the minimal and routine TEs and the CNR and incidence of the T2 shine-through effect between b values of 1000 and 3000 s/mm 2 . Inter-reader agreement was also evaluated., Results: The SNR at both b values was significantly higher, and the subjective overall image quality at a b value of 3000 s/mm 2 was significantly better at the minimal TE than at the routine TE (P < 0.05 for all). The CNR at both TEs and the incidence of the T2 shine-through effect at the minimal TE were significantly lower at a b value of 3000 s/mm 2 than at a b value of 1000 s/mm 2 (P < 0.05 for all). Inter-reader agreement was excellent., Conclusion: Liver DWI at the ultrahigh b value can reduce the T2 shine-through effect with improvement of image quality using the minimal TE.

Background: Approximately 8300 hemophiliacs are registered in Japan, but no comprehensive reports on hepatobiliary and pancreatic surgery (HBPS) have been conducted. This report investigates the current status of HPBS in hemophilia patients in Japan., Methods: The subjects were hemophiliac patients seen between January 1 2007, and December 31 2017, at facilities participating in this study among the facilities for performing high-difficulty cases nationwide designated by the Japanese Society for HBPS. A retrospective examination of short-term outcomes in 49 cases was conducted to assess patient background, disease, surgical procedure, and complications., Results: The types of hemophilia were A: 43 cases, B: four cases, and von Willebrand disease: two cases (hemophilia severity: mild 32, moderate seven, severe 10). The target malignant diseases for surgery were hepatocellular carcinoma (HCC) in 20 cases, intrahepatic cholangiocellular carcinoma (CCC) in four cases, combined HCC-CCC in two cases, hilar CCC in two cases, and pancreatic cancer in four cases. As for the surgical procedure, limited resection (subsegmentectomy and partial hepatectomy) was performed in 16 cases of HCC even with normal liver function tests. Pancreaticoduodenectomy and distal pacreatectomy were performed for pancreatic cancers as in the standard procedure. Postoperative complications were postoperative bleeding in two cases after hepatectomy and one after pancreatectomy in one case. When compared with Japanese National Clinical Data base, the complication rates after hepatectomy and pancreatectomy were not conspicuous in hemophilic patients., Conclusions: As long as they are performed in qualified centers, complication rate is not increased in hemophilic patients undergoing HBPS., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Purpose: To compare the estimated quantity of intratumor gadoxetic acid retention using T1 mapping of gadoxetic acid-enhanced magnetic resonance imaging (MRI) versus conventional processing methods for the differential diagnosis of focal liver lesions., Methods: Seventy patients with hepatic lesions (colorectal metastasis (CRM) [n = 28], hepatocellular carcinoma (HCC) [n = 20], hemangioma [n = 12], and intrahepatic cholangiocarcinoma (ICC) [n = 10]) underwent gadoxetic acid-enhanced MRI, including pre- and post-contrast T1-weighted imaging and T1 mapping. Quantitative analyses included the lesion-to-liver signal intensity ratio (SIR) on hepatobiliary phase images, the pre- and post-contrast lesion T1 value difference (ΔT1 [ms]), and the lesion retention index (LRI [%]), which was the estimated intralesional gadoxetic acid retention calculated on pre- and post-contrast T1 maps using a two-compartment pharmacokinetic model. Results were compared between the four subcategories of focal liver lesions using the Kruskal-Wallis test, followed by the post-hoc Dunn's test and receiver operating characteristic (ROC) analysis to distinguish between pairs of the four lesion subcategories., Results: This study identified significant differences in the LRI of the four lesion subcategories (p <  0.01), without significant differences in ΔT1 or SIR. Post-hoc analysis demonstrated significant differences in CRM vs. hemangioma (p <  0.01), hemangioma vs. ICC (p <  0.01), and HCC vs. ICC (p =  0.047) for the LRI., Conclusions: The quantity of intratumor gadoxetic acid retention estimated using pre- and post- contrast T1 mapping could distinguish focal liver lesions, unlike conventional processing methods, and captured unique lesion characteristics., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: To evaluate the clinicopathological and computed tomography (CT) and magnetic resonance imaging (MRI) findings of steatohepatitic hepatocellular carcinoma (SH-HCC)., Materials and Methods: Clinicopathological and radiological features were evaluated in 20 patients with SH-HCC. The diagnosis of SH-HCC was made histologically if the tumour had four of the following five characteristics: steatosis (>5% tumour cells), ballooning, Mallory-Denk bodies, interstitial fibrosis, and inflammation. All patients underwent dynamic CT and MRI. CT and MRI images were reviewed for morphological features including tumour size, presence, and distribution of fat, and patterns and degree of contrast enhancement., Results: Obesity, hypertension, and history of heavy alcohol intake were common clinical findings observed in 10 (50%), 13 (65%), and 11 (55%) of the 20 patients, respectively. Steatosis and steatohepatitis were pronounced in the background liver in 12 (60%) and 10 (50%) patients, respectively. SH-HCC was moderately differentiated in 18 patients (90%) and well differentiated in two (10%). Pathologically, steatohepatitic features were diffuse in 12 (60%) of the 20 tumours and focal in eight (40%). Tumour size and the percentage of intratumoural steatosis were not correlated (r=0.17, p=0.47). On CT, 16 (80%) patients showed arterial phase enhancement and delayed washout. On MRI, 16 (80%) of 20 tumours showed prominent fatty deposition (10 diffusely, six focally) with arterial phase enhancement., Conclusions: SH-HCC is likely to show prominent fatty deposits with arterial phase enhancement on CT and MRI. A hypervascular lesion with prominent fatty change should raise the diagnostic suspicion of SH-HCC., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors., Methods: Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations., Results: The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy., Conclusions: These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

The patient was a 67-year-old man with multiple liver metastases from sigmoid colon cancer and had received capecitabine, oxaliplatin, and bevacizumab(CAPOX plus Bev)combination chemotherapy. After 11 courses of this therapy, he had a rupture of esophageal varices and was treated with endoscopic variceal ligation(EVL). Esophageal varices are rare during the course of oxaliplatin-based chemotherapy. More studies are necessary for early detection of esophageal varices during this therapy.

Background: Recent improvements in imaging technologies have enabled surgeons to perform precise planning using virtual hepatectomy (VH). However, the practical and clinical benefits of VH remain unclear. This study sought to assess how three-dimensional analysis using a VH contributed to preoperative planning and postoperative outcome in patients undergoing liver surgery for the treatment of colorectal liver metastases (CRLM)., Methods: From 2007 to 2017, a total of 473 CRLM patients who received curative hepatectomy were retrospectively assessed. A 1:1 matched propensity analysis was performed between patients who did not receive a VH (without 3D group: n = 188) and received a VH (3D(+) group: n = 285)., Result: The rate of VH increased over the study period (P < 0.001). After propensity score matching (n = 150 for each group), no significant differences were observed in the intraoperative and postoperative outcome, including liver transection time, blood loss, or morbidity between the groups. More patients received a small anatomical resection (plus limited resections) in the 3D(+) group (25 vs 11%, [P = 0.03]). A submillimeter margin was less frequent in the 3D(+) group. No significant differences in the 5-year overall survival and disease-free survival rates were seen between the without 3D group and the 3D(+) group (38.0 vs. 45.9% [P = 0.99], 11.1 vs. 21.7%, respectively [P = 0.109])., Conclusion: Although VH did not significantly influenced on the long-term outcome after hepatectomy, a more parenchymal-sparing operative procedure (anatomical resections, plus limited resections) was selected and the risk of a submillimeter surgical margin was reduced after introduction of VH.

Background: Whether non-colorectal non-neuroendocrine liver metastasis (NCNNLM) should be treated surgically remains unclear., Methods: Data regarding 1,639 hepatectomies performed between 2001 and 2010 for 1,539 patients with NCNNLM were collected from 124 institutions. Patient characteristics, types of primary tumor, characteristics of liver metastases, and post-hepatectomy outcomes were analyzed., Results: The five most frequent primary tumors were gastric carcinoma (540 patients [35%]), gastrointestinal stromal tumor (204 patients [13%]), biliary carcinoma (150 patients [10%]), ovarian cancer (107 patients [7%]), and pancreatic carcinoma (77 patients [5%]). R0/1 hepatectomy was achieved in 90% of patients, with 1.5% in-hospital mortality rate. Overall and disease-free survival rates of 1,465 patients included in survival analysis were 41% and 21%, respectively, at 5 years, and 28% and 15%, respectively, at 10 years. Five-year survival associated with the five frequent primary tumors were 32%, 72%, 17%, 52%, and 31%, respectively, and factors predictive of a poor outcome differed by the primary tumor type., Conclusions: Our data indicated that hepatectomy is safe for NCNNLM and that patient prognoses vary depending on the type of primary tumors. Indications for hepatectomy should be determined with reference to survival rates and risk factors specific to each of the various types of primary tumor., (© 2018 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Farnesoid X receptor (FXR) is a receptor for bile acids and plays an important role in the regulation of bile acid metabolism in the liver. Although FXR has been shown to affect hepatocarcinogenesis through both direct and indirect mechanisms, potential roles of FXR in epithelial–mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) remain unclear. We examined the effect of several FXR ligands on EMT-related morphological changes in HCC cell lines, such as HuH-7 and Hep3B cells. FXR agonists (chenodeoxycholic acid, GW4064, and obeticholic acid)—but not an antagonist (guggulsterone)&mdash;induced actin polymerization and expression of N-cadherin and phosphorylated focal adhesion kinase, although they were less effective than transforming growth factor β (TGF-β). FXR agonist treatment enhanced TGF-β-induced EMT morphologic changes and FXR antagonist inhibited the effect of TGF-β. Thus, FXR activation enhances EMT in HCC and FXR antagonists may be EMT-suppressing drug candidates.

Objective: To evaluate prospectively the efficacy and safety of sorafenib, which has been the first-line treatment for advanced hepatocellular carcinoma (HCC), in Japanese HCC patients (pts) with not only Child-Pugh (C-P) A class but also C-P B class., Methods: Sorafenib was administered orally at the dose of 400 mg twice daily for pts with HCC and liver function of C-P score of 5-8. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint was time to progression (TTP), and toxicity and the secondary endpoints included objective response, overall survival (OS)., Results: Forty C-P A pts and 12 C-P B pts were enrolled. The median TTP in the C-P A pts and C-P B pts was 3.3 months and 3.2 months, respectively. Among the pts with C-P A, complete response, partial response, and stable disease were achieved for 2.5%, 7.5% and 47.5%. Among the pts with C-P B, there were no treatment responses, 66.7% of pts had stable disease. The median OS in the C-P A pts and C-P B pts was 13.4 months and 7.4 months, respectively. With regard to toxicities, fewer C-P A pts experienced Grade 3/4 toxicities than C-P B pts (77.5% vs. 91.6%). There were no treatment-related deaths in either group of patients., Conclusions: This study shows sorafenib has similar effectiveness in the recent post-approval studies and is well-tolerated in Japanese pts with HCC and Child Pugh A class. Sorafenib should be used with great care for Child Pugh class B pts.

The innate immune system, which includes toll-like receptor (TLR) signaling, plays an important role in inflammation and oncogenesis. Although TLR common adaptor myeloid differentiation factor 88 (MyD88) is known to have multiple effects on carcinogenesis, the role of MyD88 in hepatocarcinogenesis remains unknown. In this study, MyD88 expression was examined in 105 samples of human hepatocellular carcinoma (HCC) tissue by immunohistochemistry, Western blot, and quantitative reverse-transcriptase polymerase chain reaction methods. The relationships between MyD88 expression and clinical and pathological parameters were analyzed. The results showed that attenuated expression of MyD88 in HCC tissue tumor cells was significantly related to hepatitis B virus infection, large tumor size, positive vascular invasion, and intrahepatic metastasis (P < 0.05). Western blot analysis of MyD88 protein in nine normal livers and 28 HCCs showed gender disparity (P < 0.01, P < 0.05), and attenuated expression in cirrhotic livers (P < 0.05). Low expression of MyD88 mRNA was evident in HCCs with vascular invasion (P < 0.01). In contrast to previous reports, these results suggest that attenuated expression of MyD88 in HCC is associated with tumor progression., (© 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Objectives: To evaluate the longitudinal risk to patients with cirrhosis of hypervascular hepatocellular carcinoma (HCC) developing from hypovascular hepatic nodules that show positive uptake of gadoxetic acid (hyperintensity) on hepatocyte phase images., Methods: In 69 patients, we evaluated findings from serial follow-up examinations of 633 hepatic nodules that appeared hypovascular and hyperintense on initial gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) until the nodules demonstrated hypervascularity and were diagnosed as hypervascular HCC. Cox analyses were performed to identify risk factors for the development of hypervascular HCCs from the nodules., Results: The median follow-up was 663 days (range, 110 to 1215 days). Hypervascular HCCs developed in six of the 633 nodules (0.9 %) in five of the 69 patients. The only independent risk factor, the nodule's initial maximum diameter of 10 mm or larger, demonstrated a hazard ratio of 1.25. The one-year risk of hypervascular HCC developing from a nodule was 0.44 %. The risk was significantly higher for nodules of larger diameter (1.31 %) than those smaller than 10 mm (0.10 %, p < 0.01)., Conclusions: Hypervascular HCC rarely develops from hypovascular, hyperintense hepatic nodules. We observed low risk even for nodules of 10 mm and larger diameter at initial examination., Key Points: • Hypervascularization was rare on follow-up examination of hypovascular, hyperintense nodules • The risk of hypervascularization in a nodule increased with large size • Hypovascular, hyperintense nodules require neither treatment nor more intense follow-up.

Background & Aims: Human hepatocarcinogenesis in cirrhosis is thought to be multistep and characterized by a spectrum of nodular lesions, ranging from low to high grade dysplastic nodules (LGDN and HGDN) to early and progressed hepatocellular carcinoma (eHCC and pHCC). The aim of this study was to investigate the morphophenotypical changes of this sequence and their potential translational significance., Methods: We scored the vascular profile, ductular reaction/stromal invasion and overexpression of five biomarkers (GPC3, HSP70, GS, CHC, and EZH2), in a series of 100 resected nodules (13 LGDN, 16 HGDN, 42 eHCC and 29 small pHCC)., Results: The score separated the four groups of nodules as individual entities (p<0.01). In the sequence, biomarker's overexpression progressively increased with parallel decrease of ductular reaction; the vascular remodeling started very early (LGDN) but did not further develop in a proportion of HCC. eHCC was the most heterogeneous entity, with marginal overlap with HGDN and pHCC. Liver environment (fibrosis, etiology) did not impact on the phenotype of the different nodules. A subclass of eHCC (16/42) without evidence of stromal invasion was identified, suggesting a "preinvasive stage" (p<0.05). For diagnosis, the application of four and five biomarkers (rather than the usual three) improved the sensitivity of the assay for the detection of eHCC (76% and 93% vs. 52%); biomarkers in alternative combinations, and also increased the sensitivity of the assay (GS+CHC+EZH2: 76%; GS+CHC+EZH2+HSP70: 90%)., Conclusions: This study supports the multistep nature of human hepatocarcinogenesis, and suggests that eHCC is more heterogeneous than previously thought. This provides further information of the potential translational significance into clinical practice., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: We investigated the added value of the hypointensity on hepatocyte-phase (HP) imaging of gadoxetic acid-enhanced MRI (EOB-MRI) in the 2014 version of the Liver Imaging Reporting and Data System (LI-RADS) for distinguishing hepatocellular carcinoma (HCC) from benign hepatic lesions in patients with chronic liver disease., Methods: We retrospectively evaluated targeted lesions (111 HCCs, 28 benign hepatic lesions) of 139 patients (101 men, 38 women; aged 18 to 89 years, mean age, 68 ± 11 years) with chronic liver disease. EOB-MRI and dynamic contrast-enhanced computed tomography (CECT) were performed within 3 months. Two abdominal radiologists independently reviewed 3 imaging datasets: (1) EOB-MRI without an HP image using the LI-RADS system (MR imaging without HP); (2) EOB-MRI with an HP image using a modified version of the LI-RADS system in which hypointensity on the HP image was used as an additional major criterion of malignancy (MR imaging with HP); and (3) dynamic contrast-enhanced computed tomography (CECT) images using the LI-RADS system. We evaluated intra- and inter-reader agreement with kappa statistics along with 95% confidence intervals and compared diagnostic sensitivity and specificity of the 3 imaging datasets with McNemar's test., Results: The sensitivities of MR imaging were statistically higher with HP (Reader 1, 95% [107/111]; Reader 2, 95% [106/111]) than without HP (Reader 1, 84% [93/111], P = 0.002; Reader 2, 86% [96/111], P = 0.002). Specificity was comparably high between MR imaging with HP (Reader 1, 96% [27/28]; Reader 2, 96% [27/28]) and dynamic CECT (Reader 1, 100% [28/28], P = 0.317; Reader 2, 100% [28/28], P = 0.317) and MR imaging without HP (Reader 1, 96% [27/28], P = 1.00; Reader 2, 100% [28/28], P = 0.317)., Conclusion: The use of an HP image from EOB-MRI as an additional major criterion improved the sensitivity of LI-RADS to distinguish HCCs from benign hepatic lesions while retaining high specificity.

Background: Intrahepatic cholangiocarcinomas develop through a multi-step carcinogenesis. Precancerous lesions are defined as biliary intraepithelial neoplasia. Sex determining region Y-box9 (Sox9) is required for the normal differentiation of the biliary tract., Aims: To evaluate the Sox9 expression in carcinogenesis and its correlation with clinicopathological features in intrahepatic cholangiocarcinoma., Methods: Sox9 expression in normal epithelium, biliary intraepithelial neoplasia, and intrahepatic cholangiocarcinoma were investigated immunohistochemically using 43 specimens of intrahepatic cholangiocarcinoma. Sox9 expression in intrahepatic cholangiocarcinoma was compared with the clinicopathological features. The molecular effects of Sox9 were investigated by gene transfection to intrahepatic cholangiocarcinoma cell lines., Results: Sox9 expression was decreased from the normal epithelium to the biliary intraepithelial neoplasia in a stepwise fashion. In 51.2% (22/43) of the patients with intrahepatic cholangiocarcinoma, Sox9 expression was positive, and Sox9 expression was significantly associated with the biliary infiltration (P=0.034) and poor overall survival (P=0.039). Upregulation of Sox9 promoted the cell migration and invasion, and decreased the E-cadherin expression and increased the vimentin and α-SMA expression in cell lines., Conclusions: Decreased Sox9 expression may be related to the early stage of the carcinogenesis of intrahepatic cholangiocarcinoma. Sox9 overexpression in intrahepatic cholangiocarcinoma is related to biliary infiltration and poorer prognosis, and it promotes cell migration and invasion, via the epithelial-to-mesenchymal transition., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

We report the case of a 58-year-old man referred to our hospital for liver tumor treatment. The patient had a history of neurosurgery for a meningeal hemangiopericytoma 16 years previously. Pre-operative imaging revealed a hypervascular tumor extending from Couinaud segment 4 to segment 8 of the liver, measuring 95 mm in diameter, indicating an atypical hepatocellular carcinoma. Because right trisectionectomy of the liver was considered to be high risk, living-donor liver transplantation (LDLT) was indicated. After transcatheter arterial embolization, LDLT was performed with the use of a left-lobe liver graft from the patient's son. Post-operative histological findings of the liver tumor were identical to those for meningeal hemangiopericytoma, therefore the patient was diagnosed with meningeal hemangiopericytoma that had metastasized to the liver. After LDLT, the patient had a healthy, active life for 2 years; then, a subcutaneous relapse was discovered in the left chest. The patient did not undergo any systemic chemotherapy in response to the relapse. After thoracic and orthopedic surgeries and radiotherapy for multiple metastases, the patient died 5 years and 5 months after LDLT. LDLT could be an effective treatment for localized metastatic hemangiopericytoma in the liver, but it should be indicated only for carefully selected patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Hepatocellular adenoma (HCA) is a rare primary benign tumor of the liver, which occurs predominantly in young and middle-aged women. Recently, the subclassification of HCA was proposed by the Bordeaux group. Subsequently, characteristic radiological and clinical features have been revealed in each HCA subtype. According to the previous literature, diffuse intratumoral fat deposition is a very common finding in hepatocyte nuclear factor 1α-negative HCA, but this finding has been reported in β-catenin-positive HCA in the literature for only one case. In this case report, we report the second case of β-catenin-positive HCA with MR imaging sign of diffuse intratumoral fat deposition, confirmed immunohistologically on the basis of a surgical specimen. In addition, our case showed hypovascularity and isointensity on the hepatobiliary phase which have been reported as characteristic findings in β-catenin-positive HCA. Diffuse intratumoral fat deposition can be observed in β-catenin-positive HCA, which has a greater probability of malignant transformation than other types of HCA.

Hepatocellular carcinoma (HCC) develops via multistep hepatocarcinogenesis, during which hypovascular/early HCC precedes the typical hypervascular HCC. The hypovascular HCC lacks the typical hallmark imaging features of HCC, such as late arterial phase enhancement and portal venous washout, limiting early detection using conventional extracellular contrast agents for dynamic magnetic resonance imaging (MRI) or computed tomography (CT) imaging. In recent years, gadolinium-based contrast agents with hepatobiliary uptake have garnered interest from radiologists and hepatologists due to their potential for improved detection of HCC during hepatobiliary phase MRI. Lesions with reduced or absent hepatocyte function appear hypointense in the hepatobiliary phase of gadoxetic acid-enhanced MRI. This behavior can be exploited for earlier detection of hypovascular HCC. This review describes the general characteristics and advantages of gadoxetic acid for the diagnosis of HCC with a particular focus on hypovascular/early HCC., (© 2014 Wiley Periodicals, Inc.)

We report a case of typical fibrolamellar hepatocellular carcinoma (FL-HCC) in a 16-year-old Japanese boy. This is very rare malignancy in Japan. The patient was referred for investigation of a large hepatic tumor and the results of tests for hepatitis B virus surface antigen and hepatitis C virus antibody were negative. Liver function test results and serum alpha-fetoprotein (AFP) levels were normal; however, the prothrombin induced by vitamin K absence/antagonist II was elevated. Computed tomography (CT) showed a large lobulated heterogeneously enhanced tumor in the posterior section of the liver. We diagnosed FL-HCC and performed posterior sectionectomy of the liver. The resected specimen contained a light brown and green tumor with a central fibrous scar, 10.0 cm in diameter. Microscopic and electron microscopic examinations revealed the typical features of FL-HCC. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7, but negative for CK19 and AFP. The patient was alive without recurrence 48 months after surgery. Following this case report, we summarize the clinical features of the Japanese cases documented in the literature.

Purpose: To determine whether the presence of a hypovascular nodule in the liver showing hypointensity on hepatocyte-phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) is a risk factor for hypervascular hepatocellular carcinoma (HCC) in patients with chronic liver disease., Materials and Methods: Forty-one patients with pathologically confirmed hypervascular HCC and 41 age- and gender-matched controls were retrospectively selected. These patients had undergone EOB-MRI at least twice: the latest EOB-MRI and EOB-MRI performed more than 6 months earlier. History of hypervascular HCC, presence of a hypointense hypovascular nodule in previous hepatocyte-phase MR images, percent prothrombin time, platelet count, serum levels of albumin, total bilirubin, aspartate aminotransferase, alanine aminotransferase, α-fetoprotein, and protein induced by vitamin K absence-II (PIVKA-II) were variables evaluated by multivariate logistic regression analysis., Results: Multivariate analysis revealed that serum albumin level (odds ratio [95% confidence interval], 0.19 [0.06-0.57]; P = 0.0024), history of hypervascular HCC (8.62 [2.71-32.8]; P = 0.0001), and presence of a hypointense hypovascular nodule (4.18 [1.18-17.2]; P = 0.0256) were significant risk factors for hypervascular HCC., Conclusion: Patients with chronic liver disease showing a hypointense hypovascular nodule in the liver on hepatocyte-phase EOB-MRI have a high risk of HCC development., (Copyright © 2013 Wiley Periodicals, Inc.)

Twelve hepatocellular nodules were characterized in the resected livers from 3 patients (2 men and a woman) with alcoholic cirrhosis. Imaging techniques suggested that the nodules were hypervascular and may be hepatocellular carcinoma. Five nodules (4-31 mm in diameter) were serum amyloid A-positive hepatocellular neoplasm, which shares features with inflammatory hepatocellular adenoma. The remaining 7 nodules (5-8 mm) were focal nodular hyperplasia-like nodules showing focal or no immunostaining for serum amyloid A. The serum amyloid A-positive hepatocellular neoplasms showed increased cellular density, inflammatory infiltrate, sinusoidal dilatation, and ductular reaction to various degrees. These histologic features tended to be less extensive in focal nodular hyperplasia-like nodules. Three of 4 serum amyloid A-positive hepatocellular neoplasms showed slight hypointensity in the hepatobiliary phase on the magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) enhancement. In contrast, 3 focal nodular hyperplasia-like nodules showed iso-intensity in the hepatobiliary phase. This study further confirms characteristics of serum amyloid A-positive hepatocellular neoplasm arising in alcoholic cirrhosis that share features with inflammatory hepatocellular adenomas. Serum amyloid A-positive hepatocellular neoplasms sometimes co-exist with focal nodular hyperplasia-like nodules and may show different findings on Gd-EOB-enhanced MR imaging.

Objectives: To assess the value of hepatic arterial-phase (HAP) imaging with a low tube voltage (80 kVp), using non-helical, volumetric acquisition with a 320-detector-rows area-detector CT (ADCT) scanner for evaluating hypervascular hepatocellular carcinoma (HCC) compared with routine 120-kVp HAP imaging., Methods: This study enrolled 128 patients with 148 HCCs. Seventy-six patients with 79 HCCs underwent HAP imaging with 80 kVp obtained using a 320-detector-rows ADCT scanner. The remaining 52 patients with 69 HCCs underwent routine HAP imaging with 120 kVp obtained by 64-slice helical acquisition. Image noise and tumor to liver contrast-to-noise ratio (CNR) of the two sets of images were compared. Three radiologists evaluated both sets of images using receiver operating characteristic analyses., Results: Although there was a two-fold increase in the mean image noise with 80 kVp over that with 120 kVp (p < 0.001), no significant differences were observed in CNR among the two sets. The mean area under the curve (Az value) and the sensitivity for detecting HCC with 80 kVp (0.980, 78/79, respectively) were higher than that of 120 kVp (0.892, 55/69, respectively)., Conclusions: HAP imaging with 80 kVp obtained by an ADCT scanner significantly improves the diagnostic performance for evaluating hypervascular HCC.

Purpose: To compare diffusivity values between malignant and benign focal hepatic lesions using the intravoxel incoherent motion model., Materials and Methods: This study included 84 focal hepatic lesions in 84 patients. Final diagnoses were as follows: hepatocellular carcinoma (n = 45), cholangiocarcinoma (n = 6), metastatic liver tumor (n = 3), cyst (n = 20), hemangioma (n = 5), inflammatory pseudotumor (n = 2), abscess (n = 2), and focal nodular hyperplasia (n = 1). Diffusion-weighted images at 12 b-values were used to obtain the diffusion coefficient of pure molecular diffusion (D), diffusion coefficient of microcirculation or perfusion-related diffusion (D*), and perfusion-related diffusion fraction (f). Parameters of malignant and benign focal hepatic lesions were compared using the Wilcoxon test. The diagnostic performance for distinguishing between malignant and benign hepatic lesions was also analyzed., Results: Both the D value (1.15 ± 0.21 × 10(-3) mm(2) /s [mean ± standard deviation]) and D* value (62.7 ± 12.7 × 10(-3) mm(2) /s) in malignant lesions was significantly lower than that in benign lesions (D value [2.46 ± 0.45× 10(-3) mm(2) /s], P < 0.0001; D* value [87.6 ± 35.3 × 10(-3) mm(2) /s], P = 0.0008). The f value did not differ significantly between malignant (25.0 15.1 ± 15.1%) and benign lesions (30.1 ± 16.3%)., Conclusion: D* and D values were suppressed in malignant lesions. However, the D value was more reliable for distinguishing between malignant and benign focal hepatic lesions., (Copyright © 2012 Wiley Periodicals, Inc.)

Hypointensity in the hepatocyte phase is believed to be a key feature of hypovascular early hepatocellular carcinoma, which indicates malignancy. The 3 cases we present suggest that the converse is not true. Three small hepatocellular lesions showed isointensity/hyperintensity on gadoxetic acid-enhanced, hepatocyte-phase magnetic resonance images and were pathologically confirmed as early hepatocellular carcinomas. We conclude that isointensity or hyperintensity in the hepatocyte phase does not always represent benignity of hepatocellular lesions in the cirrhotic liver.

Objective: To examine if liver stiffness measured by magnetic resonance elastography (MRE) is a risk factor for hepatocellular carcinoma (HCC) in patients with chronic liver disease., Methods: By reviewing the records of magnetic resonance (MR) examinations performed at our institution, we selected 301 patients with chronic liver disease who did not have a previous medical history of HCC. All patients underwent MRE and gadoxetic acid-enhanced MR imaging. HCC was identified on MR images in 66 of the 301 patients, who were matched to controls from the remaining patients without HCC according to age. MRE images were obtained by visualising elastic waves generated in the liver by pneumatic vibration transferred via a cylindrical passive driver. Risk factors of HCC development were determined by the odds ratio with logistic regression analysis; gender and liver stiffness by MRE and serum levels of aspartate transferase, alanine transferase, alpha-fetoprotein, and protein induced by vitamin K absence-II., Results: Multivariate analysis revealed that only liver stiffness by MRE was a significant risk factor for HCC with an odds ratio (95 % confidence interval) of 1.38 (1.05-1.84)., Conclusion: Liver stiffness measured by MRE is an independent risk factor for HCC in patients with chronic liver disease.

The purpose of this study was to evaluate three-dimensional images of liver tumours obtained with gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced MRI (3D-EOB-MRI) in hepatic surgery. We conclude that 3D-EOB-MRI may be an alternative method for depicting liver tumours adjacent to the hepatic veins and portal branches, and may provide additional information for surgical planning.

Background/purpose: The origin of cholangiolocellular carcinoma (CoCC) is still controversial. To solve this problem, morphometric and immunohistochemical features of CoCC were examined., Materials and Methods: Cancerous ducts: 15 CoCC lesions from 13 resected and two autopsied cases. Non-neoplastic ducts: 20 specimens of non-cancerous areas of eight resected CoCC cases and of 12 resected hepatocellular carcinoma (HCC) cases. From these specimens, cholangioles, interlobular ducts of small size (ILD-S), interlobular ducts of medium size (ILD-M) and septal ducts were randomly selected. MORPHOMETRY: The outer and inner diameters of these ducts were measured. Immunohistochemistry: two hepatocyte markers [Hep Par 1 and α-fetoptotein (AFP)], two cholangiocyte markers (cytokeratin CK7, CK19), a marker for mucin (Muc1), a hepatic stem/progenitor cell marker (c-Kit) and epithelial membrane antigen (EMA) were used., Results: Morphometry: both mean values of the outer and inner diameters of CoCC were far larger than those of cholangioles, and showed intermediate values between those of ILD-S and ILD-M. Immunohistochemistry: all ducts of CoCCs were negative for the two hepatocyte markers and positive for CK 7. Most CoCC ducts were positive for CK 19. Positive rate of c-Kit of cholangiole was most remote from that of CoCC. The positive rates of EMA in the membranous area of ducts were similarly very high in CoCC, cholangiole and ILD-S., Conclusion: These results suggest that CoCCs may originate from ILDs.

Purpose: We evaluated the effect of intravenous administration of gadoxetic acid disodium to hepatic lesions and liver parenchyma on T₂-weighted (T₂WI) and diffusion-weighted imaging (DWI)., Materials and Methods: One hundred and one consecutive patients with 259 hepatic lesions underwent T₂WI and DWI (b-values of 500 and 1000 s/mm²) before and after gadoxetic acid administration. We compared the ratio of signal intensity (SIR) of the liver parenchyma and hepatic lesions, the ratio of contrast intensity of the lesion to the liver (CIR), the apparent diffusion coefficients (ADCs) of the liver and lesions, and lesion detectability between pre- and post-contrast images., Results: SIRs, CIRs, and ADC of focal hepatic lesions were comparable on pre- and post-contrast images, and lesion detectability did not differ significantly between pre- and post-contrast T₂WI and DWI. The SIRs of the liver parenchyma were significantly lower on post-contrast DWI (1.4±0.68 [b=500 s/mm²] and 1.71±0.67 [b=1000 s/mm²]) than pre-contrast images (1.89±0.68 [b=500 s/mm²] and 2.26±0.78 [b=1000 s/mm²]) (P<0.001). ADCs of the liver parenchyma were also significantly decreased on post-contrast DWI (0.77±0.32 mm²/s) than pre-contrast images (0.64±0.33 mm²/s) (P=0.001)., Conclusion: T₂WI and DWI after administration of gadoxetic acid are feasible and do not compromise the SIR, CIR, and ADC of focal hepatic lesions. However, the signal intensity of DWI and ADC value of the liver parenchyma were decreased on gadoxetic acid-enhanced hepatocyte phase images.

Purpose: To describe imaging findings of early hepatocellular carcinoma (HCC) at gadoxetic acid-enhanced magnetic resonance (MR) imaging, dynamic contrast material-enhanced computed tomography (CT), CT during arterial portography (CTAP), and CT during hepatic arteriography (CTHA) and to compare the diagnostic performance of each modality for small (≤ 2 cm) HCC., Materials and Methods: The institute ethics committee deemed study approval unnecessary. One hundred eight resected small lesions in 64 patients were diagnosed as a dysplastic nodule (DN) (n = 12), progressed HCC (n = 66), or early HCC (n = 30). All but two patients underwent all imaging examinations. The imaging characteristics of the lesions with each modality were determined. To evaluate the diagnostic performance of the modalities, two radiologists graded the presence of HCC with use of a five-point confidence scale. The area under the receiver operating characteristic curve (A(z)), sensitivity, and specificity of each modality were compared., Results: The imaging features that are statistically significant for differentiating an early HCC from a DN include fat-containing lesions at dual-echo T1-weighted MR imaging (seen in 16 of the 30 early HCCs and none of the DNs), low attenuation at unenhanced CT (seen in 13 of the 30 early HCCs and none of the DNs), low attenuation at CTAP (seen in 11 of the 30 early HCCs and none of the DNs), and low signal intensity at hepatocyte phase gadoxetic acid-enhanced MR imaging (seen in 29 of the 30 early HCCs and none of the DNs). The diagnostic performance of gadoxetic acid-enhanced MR imaging (A(z), 0.98 and 0.99) was significantly greater than that of contrast-enhanced CT (A(z), 0.87) and CTHA-CTAP (A(z), 0.85 and 0.86) owing to its significantly higher sensitivity (P < .001)., Conclusion: Gadoxetic acid-enhanced MR imaging is the most useful imaging technique for evaluating small HCC, including early HCC., (© RSNA, 2011.)

Purpose: To compare the diagnostic accuracy of contrast-enhanced computed tomography (CE-CT), contrast-enhanced ultrasonography (CE-US), superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), and gadoxetic acid-enhanced MRI (Gd-EOB-MRI) in the evaluation of colorectal hepatic metastases., Materials and Methods: In all, 111 patients with colorectal cancers were enrolled in this study. Of the 112 metastases identified in 46 patients, 31 in 18 patients were confirmed histologically and the remaining 81 in 28 patients were confirmed by follow-up imaging. CE-CT, CE-US, SPIO-MRI, and Gd-EOB-MRI were evaluated. Mean (of three readers, except for CE-US) area under the receiver operating characteristic curve (A(z) ), sensitivities, and positive predictive values (PPV) were calculated. Each value was compared to the others by variance z-test or chi-square test with Bonferroni correction., Results: For all lesions, mean A(z) and sensitivity of Gd-EOB-MRI (0.992, 95% [56/59]) were significantly greater than those of CE-CT (0.847, 63% [71/112]) and CE-US (0.844, 73% [77/106]). For lesions ≤1 cm, mean A(z) and sensitivity of Gd-EOB-MRI (0.999, 92% [22/24]) were significantly greater than those of CE-CT (0.685, 26% [13/50]) and CE-US (0.7, 41% [18/44]). Mean A(z) (95% CI) of SPIO-MRI for all lesions (0.966 [0.929-0.987]) and lesions ≤ 1 cm (0.961 [0.911-0.988]) were significantly greater than those of CE-CT and CE-US. Mean sensitivity of SPIO-MRI for lesions ≤1 cm (63%, 26/41) was significantly greater than that of CE-CT., Conclusion: Gd-EOB-MRI and SPIO-MRI were more accurate than CE-CT and CE-US for evaluation of liver metastasis in patients with colorectal carcinoma., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: To intraindividually compare gadoxetic acid-enhanced magnetic resonance (MR) imaging with contrast material-enhanced multi-detector row computed tomography (CT) in detection of pancreatic carcinoma and liver metastases., Materials and Methods: The ethics committee approved this retrospective study with waiver of informed consent. This study included 100 patients (53 men, 47 women; mean age, 67.8 years) consisting of 54 patients with pathologically confirmed pancreatic carcinoma (mean size, 33 mm) and 46 without a pancreatic lesion. Sixty-two liver metastases (mean size, 10 mm) in 15 patients with pancreatic carcinoma were diagnosed at pathologic examination or multimodality assessment. Three readers blinded to the final diagnosis interpreted all MR (precontrast T1- and T2-weighted and gadoxetic acid-enhanced dynamic and hepatocyte phase MR images) and tetraphasic dynamic contrast-enhanced CT images and graded the presence (or absence) of pancreatic carcinoma and liver metastasis on patient-by-patient and lesion-by-lesion bases. Receiver operating characteristic analysis, McNemar test, and Fisher test were performed to compare the diagnostic performance of CT and MR imaging., Results: No significant differences were observed between CT and MR images in depiction of pancreatic carcinoma. However, MR imaging had greater sensitivity in depicting liver metastasis than did CT for two of the three readers in the MR imaging-versus-CT analysis (85% vs 69%, P = .046) and for all three readers in the lesion-by-lesion analysis (92%-94% vs 74%-76%, P = .030-.044)., Conclusion: Gadoxetic acid-enhanced MR imaging was equivalent to dynamic contrast-enhanced CT in depicting pancreatic carcinoma and had better sensitivity for depicting liver metastases, suggesting the usefulness of gadoxetic acid-enhanced MR imaging for evaluation of patients with pancreatic carcinoma., (© RSNA, 2011.)

Background/purpose: Hepatocellular carcinomas (HCCs) commonly originate from pre-malignant lesions consisting of mature hepatocytes. However, recent studies have suggested that some HCCs emerge from hepatic stem/progenitor cells because stem/progenitor cell markers and cholangiocyte markers are found in these HCCs. At the same time, the expression of stem/progenitor cell markers and cholangiocyte markers may also indicate de-differentiation and transdifferentiation of ordinary HCC cells. This study was performed to help clarify the uncertainty surrounding these HCCs., Methods: Sixty-eight surgically resected HCC lesions no larger than 5 cm were studied immunohistochemically using a hepatocyte marker (Hepatocyte), 2 cholangiocyte markers (cytokeratins CK7 and CK19), a marker for mucin (Muc1), and a hepatic stem/progenitor cell marker (C-kit)., Results: Hepatocyte, CK7, CK19, Muc1 and C-kit were positively stained in 68 cases (100%), 51 cases (75.0%), 15 cases (22.1%), 8 cases (11.8%) and 8 cases (11.8%), respectively. In those cases positive for CK7, CK19, Muc1 and C-kit, the positively stained cells formed small foci within a large area of negatively stained cells. Small-sized positive cells suggesting hepatic/stem cell origin were found rarely., Conclusions: The positivity of cholangiocyte markers, the stem/progenitor cell marker and mucin production were thought to be due to transdifferentiation of HCC cells rather than malignant transformation of stem/progenitor cells.

Purpose: To assess the value of hepatobiliary phase gadoxetic acid (EOB)-enhanced magnetic resonance imaging (MRI) for the diagnosis of early stage hepatocellular carcinoma (HCC) (<3 cm) compared to triple-phase dynamic multidetector computed tomography (MDCT)., Materials and Methods: In all, 52 patients with 60 pathologically proven HCCs underwent both EOB-enhanced MRI and triple-phase dynamic MDCT. Two radiologists independently and blindly reviewed three image sets: 1) MDCT, 2) dynamic MRI (unenhanced and EOB-enhanced dynamic MR images), and 3) combined MRI (dynamic MRI + hepatobiliary phase images) using a five-point rating scale on a lesion-by-lesion basis. Receiver operating characteristics (ROC) analysis was performed, and sensitivity and specificity were calculated., Results: The area under the ROC curve (Az) of dynamic MRI was equivalent to that of MDCT for both readers. For both readers, Az and sensitivity of combined MRI for smaller lesions (<1.5 cm) were significantly higher than that of dynamic MRI and MDCT (P < 0.0166). The majority of false-negative nodules on dynamic MRI or MDCT (75% and 62%, respectively) were due to a lack of identified washout findings., Conclusion: Hepatobiliary phase images can increase the value of EOB-enhanced MRI in the diagnosis of early stage HCC. The sensitivity and accuracy were significantly superior to MDCT for the diagnosis of lesions less than 1.5 cm., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: To retrospectively determine the findings of gadoxetic acid-enhanced magnetic resonance imaging (MRI) to distinguish hemangioma and metastasis of the liver., Materials and Methods: The University's ethics committee approved this retrospective study. We assessed 45 patients without chronic liver disease who underwent gadoxetic acid-enhanced MRI. Diagnosis of 58 metastases and 47 hemangiomas was confirmed using histopathology or multimodality evaluation. Two radiologists independently assessed the following MRI findings of metastasis and hemangioma: their appearance on T2-weighted images (T2WI) and dynamic contrast enhancement patterns after gadoxetic acid administration. The metastasis and hemangioma findings were compared using Fisher exact test. The lesion-to-liver signal intensity ratio on hepatocyte phase was compared using the Mann-Whitney U test. Multivariate analysis was performed to identify independent imaging findings distinguishing the 2 diseases. Receiver operating characteristic analysis was used to estimate the diagnostic ability of gadoxetic acid-enhanced MRI to distinguish metastasis from hemangioma., Results: The lesion-to-liver signal intensity ratio was comparable in both diseases. Peripheral-dot enhancement, ring-like, geographic, and moderate late-phase enhancement, rapid contrast filling, and bright signal on T2WI could differentiate between the 2 diseases. In multivariate analysis, bright signal on T2WI (94%-98% in hemangioma and 13%-25% in metastasis) and ring-like enhancement (4% in hemangioma and 58%-60% in metastasis) were the independent findings suggesting hemangioma and metastasis, respectively. The areas under the receiver operating characteristic curves to distinguish metastasis from hemangioma were 0.95 and 0.98 for Reader 1 and 2, respectively., Conclusion: Reliable findings to distinguish hepatic metastasis from hemangioma on gadoxetic acid-enhanced MRI were ring-like enhancement on arterial-phase images and bright signal on T2WI.

Objectives: determine the effect of double-dose gadoxetic-acid (Gd-EOB-DTPA) on lesion-liver contrast ratio in arterial- and hepatocyte-phase images and arterial-phase image quality in patients with chronic liver disease., Materials and Methods: the ethics committee at our institute approved this study. This study included 28 patients (13 with Child-Pugh class A and 15 with class B) with 54 hepatocellular carcinomas. All patients received the standard Gd-EOB-DTPA dose (0.025 mmol/kg bodyweight) and double dose (0.050 mmol/kg bodyweight). The lesion-liver contrast ratio was evaluated in arterial- and hepatocyte-phase images. The artifacts in arterial-phase images were evaluated with a 4-point scale. Wilcoxon signed-rank test were used for comparisons., Results: the hepatocyte-phase lesion-liver contrast ratio after the double dose was significantly higher than that after the standard dose in patients with Child-Pugh class B disease(standard dose vs. double dose; 0.20 ± 0.16 vs. 0.25 ± 0.17; P < 0.0001); however, the ratio after both the standard and double doses was equivalent in patients with Child-Pugh class A disease (0.35 ± 0.18 vs. 0.35 ± 0.14; P = 0.3038). The double dose significantly increased the arterial-phase lesion-liver contrast ratio (0.34 ± 0.19 vs. 0.58 ± 0.33; P < 0.0001). The artifacts in the arterial-phase images were more prominent after the standard dose (2.7 vs. 2.4 for reader 1, 2.8 vs. 2.4 for reader 2; P = 0.0195 and 0.0010)., Conclusions: administration of double dose of Gd-EOB-DTPA provided better arterial enhancement of hepatocellular carcinomas in patients with chronic liver disease, and also improved the lesion-liver contrast in hepatocyte-phase images in patients with Child-Pugh class B disease.

Complete resection for colorectal metastases is the only treatment that can provide long-term survival and may lead to cure. Recent reports have shown that liver resection following systemic chemotherapy in patients with initially unresectable metastases from colorectal cancer may also result in a good long-term survival, and rescue surgery after chemotherapy has become a strategy of choice. A 29-year-old male and a 35-year-old female with unresectable liver metastases from colorectal cancer underwent complete resection after administration of third-line combination therapy of cetuximab and irinotecan. Although systemic chemotherapy may decrease liver function, which may make liver resection unfeasible, in the two cases reported, liver function did not deteriorate after cetuximab plus irinotecan. The indocyanine green retention rate at 15 minutes, which is useful in deciding the safe limit of hepatectomy, was optimal after the administration of cetuximab plus irinotecan in both patients. Cetuximab plus irinotecan may be beneficial as neoadjuvant chemotherapy for metastatic colorectal cancer, not only because of its oncological efficacy but also for preservation of liver function.

Purpose: To compare the diagnostic accuracy of contrast-enhanced ultrasonography (CE-US), contrast-enhanced CT (CE-CT), and superparamagnetic iron oxide-enhanced MRI (SPIO-MRI) with diffusion-weighted imaging (DWI) in the evaluation of colorectal hepatic metastases., Materials and Methods: Thirty-six patients with colorectal cancers were prospectively enrolled and retrospectively evaluated. Of the 86 metastases identified, 16 were confirmed histologically and the remaining 70 were confirmed by follow-up imaging. CE-CT and SPIO-MRI + DWI were independently evaluated by two readers, whereas CE-US was evaluated by consensus reading of two different readers. Area under receiver operating characteristic curve (A(z)), sensitivities, and positive predictive values (PPVs) were calculated and compared., Results: For both readers, SPIO-MRI+DWI had significantly greater A(z) (0.879 and 0.904) and sensitivity (78% and 87%) for all lesions compared with CE-CT (0.779 and 0.793; 59% and 59%) and CE-US (0.811; 69%), and significantly greater A(z) (0.783 and 0.837) and sensitivity (56% and 73%) for lesions ≤1 cm compared with CE-CT (0.562 and 0.601; 20% and 22%) and CE-US (0.66; 37%). For lesions >1 cm, there was no significant difference in A(z), sensitivity and PPV between all the image sets., Conclusion: SPIO-MRI with DWI was the most reliable modality for evaluation of liver metastases particularly for lesions ≤1 cm., (© 2010 Wiley-Liss, Inc.)

Background: Preoperative chemotherapy containing oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) causes histological liver injury and increases postoperative morbidity and mortality in patients with colorectal liver metastasis (CRLM). However, information on the aggravation of liver function and its reversibility is scarce., Methods: A total of 55 patients who underwent a hepatectomy after receiving FOLFOX and/or FOLFIRI were included in the present study. Indocyanine green tests were repeatedly performed before hepatectomy for monitoring the change of hepatic functional reserve., Results: A significant decrement in the ICG R15 value was observed at 2-4 weeks (12.9%, P = .04), 4-8 weeks (11.4%, P = .01), and 8 or more weeks (11.1%, P = .006) after the last chemotherapy, compared with results documented within 2 weeks (16.8%). However, no significant change was observed among the values obtained at 2-4 weeks, 4-8 weeks, and 8 or more weeks. The individual ICG R15 values at the beginning and end of the cessation period also improved from 17.7% to 11.6% (P = .001). Histological liver injury was associated with larger amounts of operative blood loss but not with morbidity. Neither liver failure nor mortality occurred in the present series., Conclusions: The hepatic functional reserve, represented by the ICG R15 value, improves during the period after chemotherapy cessation. The present study suggests that chemotherapy cessation for at least 2-4 weeks enables an improvement in the hepatic functional reserve, especially among patients with an abnormal ICG R15 value (> 10%) who have received 6 or more cycles of FOLFOX and/or FOLFIRI.

In the treatment of hepatocellular carcinoma (HCC), control of the tumor itself, vascular invasion, and minute intrahepatic metastases is the main important factor to be considered. Based on previously reported indirect evidence, liver resection would seem to have advantages over percutaneous ablation for single HCCs measuring between 2 and 5 cm in diameter. In conclusion, liver function permitting, resection would be the therapeutic option of first choice. In cases with poor liver functional reserve, liver transplantation would be a good therapeutic option, depending on the age of the patient.

Purpose: To retrospectively determine findings at gadoxetic acid-enhanced magnetic resonance (MR) imaging in hypervascular pseudolesions that were observed at computed tomography (CT) during hepatic arteriography, with special focus on distinguishing these pseudolesions from hypervascular hepatocellular carcinomas (HCCs)., Materials and Methods: The institute ethics committee deemed study approval unnecessary. The study population comprised 80 patients (55 men, 25 women) with chronic liver disease who underwent CT during hepatic arteriography and arterial portography, gadoxetic acid-enhanced MR imaging, and follow-up dynamic contrast material-enhanced CT. The diagnosis of 104 pseudolesions and 123 HCCs was confirmed by means of histopathologic or multimodality evaluation. Two radiologists assessed the MR imaging findings of HCCs and pseudolesions in consensus, including the signal intensities (SIs) of the lesions on T2-weighted, diffusion-weighted (DW), and contrast-enhanced hepatocyte-phase images. The findings of nodular pseudolesions and HCCs were compared with the Fisher exact test. Additionally, the hepatocyte-phase SI ratio (ratio of lesion SI to liver SI) for HCCs and pseudolesions was compared by means of the Mann-Whitney U test., Results: There were 62 wedge-shaped, 32 nodular, and 10 linear pseudolesions. On gadoxetic acid-enhanced hepatocyte-phase MR images, 15% of pseudolesions (16 of 104) were hypointense compared with surrounding liver tissue. The mean hepatocyte-phase SI ratio of HCCs (0.65 +/- 0.14 [standard deviation]) was significantly lower (P < .01) than that of the nodular pseudolesions (0.95 +/- 0.11). The optimal cutoff value of hepatocyte-phase SI ratio for distinguishing between HCC and nodular pseudolesion was 0.84. No nodular pseudolesions were visible on DW images., Conclusion: Gadoxetic acid-enhanced hepatocyte-phase MR imaging and DW imaging could be used to distinguish hypervascular pseudolesions from hypervascular HCCs; a hepatocyte-phase SI ratio below 0.84 and visibility on DW images were findings specific for HCCs rather than pseudolesions.

Background: The value of prophylactic abdominal drainage in patients undergoing hepatectomy is controversial. We carried out a retrospective study to clarify the value of this procedure., Methods: The study subjects were 1269 consecutive patients who underwent elective hepatectomy with drain insertion for malignant tumors without associated gastrointestinal procedures or bilio-enteric anastomosis. Symptomatic abdominal fluid collections were treated by the drain salvage method, percutaneous puncture, and/or re-operation, in that order of preference., Results: One patient died (mortality rate, 0.07%) and 7 patients had postoperative bleeding (0.6%). Bile leakage, found in 111 (8.7%) patients, subsided with retention of the drain in 78 (70%) and use of the drain salvage technique in 8 (7.2%), whereas percutaneous puncture and re-operation were required in 11 (9.9%) and 14 (12.6%). Symptomatic fluid collection, observed in 65 (5.1%) patients, was treated by the drain salvage technique in 20 (31%) patients, while puncture and re-operation were required in 25 (38%) and 20 (31%)., Conclusions: Placement of drains was effective in a considerable proportion of patients undergoing hepatectomy, with regard to reducing the frequency of development of subphrenic fluid collections and biliary fistula/biloma formation.

A 33-year-old man presented with pain and palsy of the leg in 2008 for treatment of hepatocellular carcinoma with huge distant metastases. The patient's tumors had slowly enlarged despite several treatments. Oral administration of sorafenib at 800 mg/day with careful observation was commenced in 2009. Laboratory investigations on day 7 showed massive tumor lysis. An abdominal CT showed multiple low density areas and tumor markers decreased, indicating extended tumor necrosis. In conclusion, clinicians should bear in mind not only the published adverse effects, but also massive tumor lysis, when treating patients with large tumor burden by sorafenib.

Purpose: To evaluate the effectiveness of diffusion-weighted magnetic resonance imaging (DWI) in estimating the grade of malignancy of hepatocellular carcinoma., Materials and Methods: Dynamic contrast-enhanced computed tomography (CE-CT) and DWI (b value, 1000 s/mm(2)) were performed on 73 patients. Using DW images, the lesions were classified as "visible" or "invisible." The apparent diffusion coefficient (ADC) of the lesions was measured. Furthermore, the lesions were classified as hypervascular or iso-hypovascular using arterial phase CE-CT images. The image findings for each lesion type were compared., Results: The 73 patients had 98 hepatocellular lesions, of which 12 were histologically diagnosed as dysplastic nodules; 39, well-differentiated HCCs; 33, moderately differentiated HCCs; and 14, poorly differentiated HCCs. The mean ADC values of moderately poorly-differentiated HCCs were significantly lower than well-differentiated HCCs and dysplastic nodules (P < 0.01). On DW images, >90% of moderately (30/33) and poorly differentiated HCCs (13/14) were visible, while 51% of well-differentiated HCCs (20/39) and all dysplastic nodules were invisible. Of 22 iso-hypovascular lesions, 4 were visible on DW images and were poorly differentiated HCCs, whereas 18 were invisible and were dysplastic nodules (12/18) or well-differentiated HCCs (6/18)., Conclusion: A combination of hypovascularity and visibility on DW images can help distinguish poorly differentiated HCCs from low-grade hepatocellular lesions (dysplastic nodules and well-differentiated HCCs).

Purpose: To elucidate whether a contrast agent dilution method (dilution method), in which gadoxetate disodium (Gd-EOB-DTPA) is diluted with saline, is useful for good-quality arterial-phase images., Materials and Methods: In this study we observed 494 hypervascular hepatocellular carcinomas (HCCs) in 327 patients with chronic liver disease. Three Gd-EOB-DTPA injection methods were adopted for comparison: 1) test injection method (undiluted Gd-EOB-DTPA and modified scan delay), in which a test dose of 0.5 mL of Gd-EOB-DTPA was injected to determine scan delay; 2) conventional method (undiluted Gd-EOB-DTPA and fixed scan delay); and (3) dilution method (diluted Gd-EOB-DTPA and fixed scan delay), in which Gd-EOB-DTPA was diluted to 20 mL with saline. Lesion-liver contrast was calculated. Image quality and lesion detectability were evaluated by two radiologists blinded to the injection methods., Results: The lesion-liver contrast of the dilution method was significantly higher than that of the other two methods. Lesion detectability of the conventional method (64%) was significantly lower than that of the other two methods (contrast agent dilution method, 95%; test injection method, 93%). The image quality of the contrast agent dilution method was significantly better than that of the other two methods., Conclusion: The dilution method contributed to improved image quality, high lesion-liver contrast, and high lesion detectability in the arterial-phase images of GD-EOB-DTPA-enhanced MRI., ((c) 2009 Wiley-Liss, Inc.)

Objective: The aim of this trial was to verify the new surgical device (the LigaSure vessels sealing system) decrease liver transection time., Summary Background Data: Among the major goals in hepatic resection are minimization of the operation time and of the blood loss. Preliminary reports have suggested that the vessel sealing system might decrease the liver transection time, which is directly associated with the amount of blood loss., Methods: Patients who were scheduled to undergo hepatic resection at the Tokyo University Hospital were assigned, by the minimization method, to either use of the new vessel sealing system (VS group) or the conventional clamp crushing method (CC group) for liver transection. The primary end point was the liver transection time, and the secondary endpoints were the amount of blood loss during the entire operation and during liver transection, length of hospital stay, postoperative liver function, and the incidence of various adverse events. An English-language summary of the protocol was submitted (registration ID: C000000337) to the Clinical Trials Registry managed by the University Hospital Medical Information Network in Japan, which can be accessed commission-free on the internet (Available at: http://www.umin.ac.jp/ctr/index.htm)., Results: From February to December in 2006, a total of 165 patients underwent liver resection for some benign or malignant disease of the liver. Among these patients, 120 were randomly assigned to the CC (n = 60) or the VS (n = 60) group. There was no mortality in either of the 2 groups. The median liver transection time in the VS group was 57 minutes (range: 11-127), similar to that in the CC group (56 [range: 9-269] min, P = 0.64), while there was no difference in the transection speed between the 2 groups (1.16 [0.15-2.26] cm/min vs. 1.10 [0.15-2.66] cm/min, P = 0.95). The amount of blood loss and blood loss per transection area during liver transaction in the VS group was also similar to that in the CC group (median: 315 [25-2415] mL vs. 315 [10-1700] mL; P = 0.80) and (5.04 [1.01-44.2] mL/cm vs. 4.36 [0.15-50.5] mL/cm; P = 0.14), respectively., Conclusions: This randomized controlled trial showed that while the vessel sealing system was safe, its use was not associated with any significant decrease of the operation time or blood loss during liver transaction as compared with that of the clamp crushing method.

Purpose: To compare the accuracy of dynamic contrast-enhanced multidetector-row computed tomography (CT) and superparamagnetic iron oxide-enhanced magnetic resonance imaging (MRI) in the evaluation of small hepatic metastases of colorectal carcinoma., Materials and Methods: Of 94 patients with colorectal carcinoma analyzed, 76 hepatic metastases (<2 cm) were diagnosed in 17 patients. Superparamagnetic iron oxide (SPIO)-magnetic resonance (precontrast and postcontrast MRI) and dynamic contrast-enhanced multidetector-row CT (dynamic CT [precontrast, arterial, portal-venous, and delayed phase]) were evaluated. The alternative free-response receiver operating characteristic analysis was performed, and the sensitivities and positive predictive values were analyzed., Results: The Az values and sensitivities of portal-venous phase CT, dynamic CT, and SPIO-MRI (0.62/59%, 0.69/61%, and 0.67/61%) were identical. The mean positive predictive value of dynamic CT (82%) was inferior to that of SPIO-MRI (91%)., Conclusions: The diagnostic ability of dynamic CT is identical to that of SPIO-MRI in Az value and sensitivity. Superparamagnetic iron oxide-MRI should be recommended only if an equivocal lesion is detected by dynamic CT.

Background: Although portal venous tumor thrombus (PVTT) is regarded as an ominous prognostic factor in patients with hepatocellular carcinoma (HCC), the optimal treatment method for maximizing both safety and long-term outcome has not yet been discussed. We describe a surgical technique in which the venous wall is peeled off from the PVTT., Methods: In the peeling off (PO) technique, the portal venotomy was placed after adequate vascular control of portal flow. The PVTT was dissected from the portal venous wall and removed through the opening. Macroscopically residual PVTTs intruding into tiny branches were meticulously extracted. This procedure was compared with the en bloc resection of PVTT. Between 1995 and 2006, 49 patients underwent curative hepatic resections for HCC with macroscopic PVTT; these patients were classified according to whether the PO technique (n = 20) or the en bloc technique (n = 29) had been utilized. Both the short- and long-term results were compared between the 2 groups., Results: No mortalities occurred in either group. Both the 5-year overall survival and the recurrence-free survival rates of the PO group were comparable with those of the en bloc group (39% vs 41% [P = .90] and 23% vs 18% [P = .89], respectively). No local recurrences or regrowth of the PVTT occurred in either group., Conclusion: Our procedure is useful for removing PVTT extending beyond the bifurcation or into other sectors that should be preserved in terms of liver function and enables a more conservative resection than an en bloc technique without sacrificing curability.