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Objectives: The characteristics of hypovascular and hypervascular well-differentiated hepatocellular carcinomas (HCCs) were compared in terms of tumor size, tumor markers and detectability by imaging modalities., Methods: Well-differentiated HCC nodules that are smaller than 2 cm (n = 27) were evaluated in 27 patients using histopathology and divided into 2 groups: hypovascular (n = 10) and hypervascular (n = 17). The diagnostic sensitivity of imaging modalities was then evaluated for efficiency in disclosing tumor size and tumor markers in the 2 types., Results: No difference was observed in tumor size and tumor markers between the 2 types; however, the sensitivity of contrast-enhanced CT, contrast-enhanced ultrasonography and arterioportal angiography was significantly different between the 2 types, whereas that by Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) demonstrated no difference., Conclusion: Hypovascular HCC could be diagnosed by Gd-EOB-DTPA MRI in the hepatobiliary phase., (© 2015 S. Karger AG, Basel.)

We describe a well-differentiated hepatocellular carcinoma (HCC) with alcohol-related liver cirrhosis in a 69-year-old man. Ultrasonography (US) disclosed a 10 mm hypoechoic nodule in segment 4; Sonazoid contrast-enhanced US and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed no defect in either the Kupffer phase or the hepatobiliary phase. Computed tomography during hepatic arteriography (CTHA), however, revealed a hypovascular nodule, but CT during arterial portography showed no perfusion defect. Histological analysis indicated a well-differentiated HCC. Thus, our detection of well-differentiated HCC disclosed by only CTHA attested to the efficiency of this modality, suggesting that it is more sensitive than Gd-EOB-GTPA-enhanced MRI.

Purpose: To retrospectively evaluate technical success, effectiveness, complications, patient survival, and prognostic factors with percutaneous radiofrequency (RF) ablation for pulmonary metastases resulting from hepatocellular carcinoma (HCC)., Materials and Methods: Thirty-two patients from six institutions were included, with a total of 83 pulmonary metastases treated in 65 sessions. RF ablation was always performed percutaneously with computed tomography (CT) guidance. Primary endpoints were technical success and technique effectiveness. Technique effectiveness was evaluated based on sequential follow-up CT images. Secondary study endpoints were complications, patient survival, and determination of prognostic factors. Complications were classified as major or minor. Prognostic factors were determined by analyzing multiple variables with the log-rank test., Results: Technical success rate was 100%. Primary technique effectiveness rates were 92% each at 1, 2, and 3 years. Major and minor complications occurred after 16 (25%) and 23 (35%) of the 65 sessions, respectively. The median follow-up period was 20.5 months. Overall survival rates were 87% at 1 year and 57% each at 2 and 3 years (median and mean survival times, 37.7 mo and 43.2 mo, respectively). Significantly better survival rates were obtained in cases of (i) no viable intrahepatic recurrence (P < .001), (ii) Child-Pugh class A disease (P < .001), (iii) absence of liver cirrhosis (P < .001), (iv) absence of hepatitis C virus infection (P = .006), and (v) α-fetoprotein level of 10 ng/mL or lower (P = .007) at the time of RF ablation., Conclusions: RF ablation appears effective, with an acceptable safety profile, in selected patients with pulmonary metastases resulting from HCC., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

Aim: To compare the imaging results with histology and to evaluate the diagnostic sensitivity of imaging modalities for hepatocellular carcinoma (HCC) smaller than 2 cm., Methods: Nodules smaller than 2 cm (n = 34) revealed by ultrasonography (US) in 29 patients with liver cirrhosis were analyzed. Histological diagnosis of HCC was performed by ultrasonographic guidance: moderately-differentiated HCC (n = 24); well-differentiated HCC (n = 10). The patterns disclosed by the four imaging modalities defined the conclusive diagnosis of HCC: (1) contrast-enhanced computed tomography (CECT), hypervascularity in the arterial phase and washout in the equilibrium phase; (2) Sonazoid contrast-enhanced US (CEUS), hypervascularity in the early vascular phase and defect in the Kupffer phase; (3) gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), hypervascularity in the arterial phase and/or defect in the hepatobiliary phase; and (4) CT arterioportal angiography: hypervascularity by CT during arteriography and/or perfusion defect by CT during arterial portography., Results: Overall, the sensitivity of diagnosing HCC smaller than 2 cm was 52.9% (18/34) (95% CI: 35.1-70.2) by CECT; 67.6% (23/34) (95% CI: 49.5-82.6) by Sonazoid CEUS; 76.5% (26/34) (95% CI: 58.8-89.3) by Gd-EOB-DTPA MRI; and 88.2% (30/34) (95% CI: 72.5-96.7) by CT arterioportal angiography. The diagnostic sensitivity of detecting moderately-differentiated HCC by CECT, Sonazoid CEUS, Gd-EOB-DTPA MRI and CT arterioportal angiography was 62.5% (15/24) (95% CI: 40.6-81.2), 79.2% (19/24) (95% CI: 57.8-92.9), 75.0% (18/24) (95% CI: 53.3-90.2) and 95.8% (23/24) (95% CI: 78.9-99.9), respectively. A significant difference (P < 0.05) was observed between CECT and CT arterioportal angiography in all nodules. There was no difference between Sonazoid CEUS, Gd-EOB-DTPA MRI, and CT arterioportal angiography. The combined sensitivity of Sonazoid CEUS and Gd-EOB-DTPA MRI was 94.1% (32/34)., Conclusion: Changing the main diagnostic modality for HCC smaller than 2 cm from CT arterioportal angiography to Sonazoid CEUS and Gd-EOB-DTPA MRI is recommended.

We describe a 15-mm scirrhous hepatocellular carcinoma (HCC) in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase. Contrast-enhanced computed tomography (CT) revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase. Magnetic resonance imaging (MRI) revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hyperintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC. Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically, the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.

Aim: To evaluate long-term follow-up of minimum-sized hepatocellular carcinoma (HCC) treated with percutaneous ethanol injection (PEI)., Methods: PEI was applied to 42 lesions in 31 patients (23 male and eight female) with HCC < 15 mm in diameter, over the past 15 years., Results: Overall survival rate was 74.1% at 3 years, 49.9% at 5 years, 27.2% at 7 years and 14.5% at 10 years. These results are superior to, or at least the same as those for hepatic resection and radiofrequency ablation. Survival was affected only by liver function, but not by sex, age, etiology of Hepatitis B virus or Hepatitis C virus, alpha-fetoprotein levels, arterial and portal blood flow, histological characteristics, and tumor multiplicity or size. Patients in Child-Pugh class A and B had 5-, 7- and 10-years survival rates of 76.0%, 42.2% and 15.8%, and 17.1%, 8.6% and 0%, respectively (P = 0.025)., Conclusion: Treatment with PEI is best indicated for patients with HCC < 15 mm in Child-Pugh class A.

Percutaneous computed tomographic (CT)-guided radiofrequency (RF) ablation is a minimally invasive and promising procedure for unresectable lung tumors. In general, the procedure is safe and its complications are minor. A few cases of serious complications, however, have been reported. The authors report on a case of air embolism during electrode insertion into a metastatic lung tumor. The patient became unresponsive; however, he recovered 10 minutes later and the air embolism disappeared spontaneously. Although air embolism during RF ablation of a lung tumor is a rare complication, radiologists performing the percutaneous procedure should be aware of this complication and be familiar with the appropriate management.

We present a rare case of well- to moderately-differentiated hepatocellular carcinoma (HCC) in a 71-year-old woman with hepatitis C virus-related cirrhosis and unusual radiologic features. A 20-mm hypoechoic nodule disclosed by ultrasound in segment two showed hyperattenuation on both computed tomography hepatic arteriography and computed tomography during arterial portography. Contrast-enhanced ultrasound revealed hypervascularity in the early vascular phase and defect in the post-vascular phase, with the same pattern detected by the two imaging techniques. SPIO-MRI revealed a hyperintense nodule. These findings were compatible with those of moderately-differentiated HCC. An ultrasound-guided biopsy showed histological features of well- to moderately-differentiated HCC characterized by more than two-fold the cellularity of the non-tumorous area, fatty change, clear cell change and mild cell atypia with a thin to mid-trabecular pattern. Further studies may provide insights into the correlation between tumor neovascularity in multistep hepatocarcinogenesis and dual hemodynamics, including the artery and the portal vein.

We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepato-cellular carcinoma (HCC) in a 56-year-old man with alcohol-related liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and contrast enhanced US revealed a hypovascular nodule, both in segment seven. US-guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced cellularity with a high N/C ratio, increased cytoplasmic eosinophilia, and slight cell atypia. One year later, the US pattern of the nodule changed from hypoechoic to hyperechoic without any change in size or hypovascularity. US-guided biopsy revealed well-differentiated HCC of the same features as shown in the first biopsy, but with additional pseudoglandular formation and moderate cell atypia. Moreover, immunohistochemical staining of cyclase-associated protein 2, a new molecular marker of well-differentiated HCC, turned positive. This is the first case of multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated HCC within one year in alcohol-related liver cirrhosis.

To evaluate the effectiveness of computed tomography (CT) arterioportal angiography in the diagnosis of hepatocellular carcinoma (HCC) in nodules smaller than 2 cm, we compared the findings of CT during arteriography (CTA) and CT during arterial portography (CTAP) with those of enhanced CT and enhanced magnetic resonance imaging (MRI). Sixty-eight nodules smaller than 2 cm in 53 patients with liver cirrhosis were classified into three groups of CTA and CTAP: (group 1) hyperattenuation on CTA, and hypoattenuation on CTAP (56 nodules, 41 patients); (group 2) hypoattenuation on CTA, and hypoattenuation on CTAP (10 nodules, 10 patients); (group 3) hypoattenuation on CTA, and hyperattenuation on CTAP (2 nodules, 2 patients). Histologically, 96% (54/56), 80% (8/10), and 100% (2/2) of the nodules in groups 1, 2 and 3, respectively, were diagnosed as HCC. In group 1, enhanced CT or enhanced MRI confirmed hypervascularity in only 77% (30/39) and venous washout in 21% (8/39). In groups 2 and 3, enhanced CT or enhanced MRI on 7 and 2 nodules, respectively, revealed no hypervascularity (0%). The results suggested that CT arterioportal angiography is superior to enhanced CT and MRI in nodules smaller than 2 cm for diagnosing HCC (p < 0.01 group 1, p < 0.01 group 2)., (Copyright 2007 S. Karger AG, Basel.)

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

A rare case of well-differentiated minute hepatocellular carcinoma (HCC) with hepatitis C virus-related cirrhosis, with unusual radiologic features, is presented. A 10-mm hypoechoic nodule disclosed by ultrasound in segment six showed hypoattenuation on computed tomography hepatic arteriography and hyperattenuation on computed tomography during arterial portography, indicating that the portal vein may have been the dominant vascularity of the nodule. Contrast-enhanced ultrasound revealed hypovascularity in the early arterial phase, isovascularity in the late vascular phase, and the same perfusion as that surrounding the liver parenchyma in the post-vascular phase, with the same pattern observed on the two imaging techniques. These findings were considered not compatible with those of well-differentiated HCC. Ultrasound-guided biopsy showed histological features of well-differentiated HCC with over two-fold the cellularity of the non-tumorous area with a high nuclear/cytoplasmic ratio, increased cytoplasmic eosinophilia, slight atypia and fatty change with an irregular thin trabecular pattern. Further studies may provide insights into the correlation between tumor neovascularity in multistep hepatocarcinogenesis and dual hemodynamics, including the artery and the portal vein.

Background/aims: The present study was conducted to accurately monitor the pattern of ethanol distribution during percutaneous ethanol injection by computed tomography fluoroscopy and to examine the relationship between the distribution pattern and therapeutic effect., Methodology: Twenty-five hypervascular hepatocellular carcinomas were studied. Each was treated with transcatheter arterial embolization. However, as residual parts were detected, percutaneous ethanol injection under real-time computed tomography fluoroscopy was performed. For analysis, ethanol distribution and local recurrence rate were compared., Results: Ethanol distribution in a tumor was classifiable into 3 patterns. In pattern 1, ethanol solution was distributed spherically. In pattern 2, ethanol solution spread forming linear boundaries indicating interruption of distribution by septa. In pattern 3, ethanol spread circumferentially only along the periphery sparing the central part of a tumor. The 6-month recurrence rate of the tumors in which ethanol solution was distributed to the whole viable part was 25% (pattern 1), 100% (pattern 2) and 0% (pattern 3), respectively., Conclusions: In the tumors showing distribution pattern 3 by computed tomography fluoroscopy, a combination therapy of transcatheter arterial embolization and percutaneous ethanol injection was more effective than in other patterns. Computed tomography fluoroscopy was useful for accurate monitoring and predicting the therapeutic effect of percutaneous ethanol injection.

We report a case of multicentric hepatocellular carcinoma that developed in a 74-year-old man 3 and 6 years after interferon (IFN) treatment for chronic hepatitis C, despite sustained virologic, biochemical, and histological improvement. Initially, serum hepatitis C virus RNA was positive and the patients' serum level of alanine aminotransferase (ALT; 82 IU/ml) was abnormal. Hepatitis B virus (HBV) in the serum was negative for surface antigen, surface antibody, core antibody, and DNA. The patient was started on 10 x 10(6) international units (IU) of IFNalpha, 3 days a week for a total of 24 weeks. After the IFN therapy, the patient demonstrated a normal serum ALT level, and was continuously negative for HCV-RNA, and histology improved from chronic active hepatitis to chronic persistent hepatitis. Follow-up studies with ultrasonography (US) every 3 months and computed tomography (CT) every 6 months revealed no space-occupying lesion (SOL) for 3 years after IFN treatment.US-guided biopsies of two 15-mm hypoechoic SOLs in segments eight (S8) and seven (S7) 34 and 74 months, respectively, after IFN treatment showed well-differentiated hepatocellular carcinoma (HCC). Clinical data, imaging studies, and histologic examinations showed that both tumors were multicentric HCC. Further studies may provide insights into the possible role of HCV in hepatocarcinogenesis in patients demonstrating HCV eradication by IFN treatment.

A new therapy complementary to transcatheter arterial embolization (TAE) in which anticancer agents are percutaneously injected into the tumor under ultrasound guidance (percutaneous injection chemotherapy combined with TAE; TAE-PICT) has been developed and found to be effective. A total of 68 hepatocellular carcinoma (HCC) nodules in 50 patients were treated with TAE-PICT, and the complications were evaluated. Among those with solitary HCC nodules < or = 5 cm in diameter, 17 were treated with TAE-PICT and 24 with only TAE in a prospective comparative study. No major complications were seen, and the anticancer drugs could still be found in the tumor 3 months after injection. A significantly higher cumulative survival rate (p= 0.03961) and significantly higher cumulative recurrence-free survival rate (p = 0.00647) were achieved in patients treated with TAE-PICT than in those treated with TAE alone.

Background/aims: Dysplastic nodules diagnosed pathologically exhibit various hemodynamic patterns. To evaluate these differences in their hemodynamics, we observed basement membrane formation of sinusoids., Methodology: For 12 low-grade dysplastic nodules, 24 high-grade dysplastic nodules and 16 hepatocellular carcinomas, both computed tomography during arterial portography and CT arteriography were performed preoperatively. Resected specimens were examined immunohistochemically for COL IV (type IV collagen) and laminin to observe basement membrane formation. We compared their hemodynamics on computed tomography during arterial portography and CT arteriography with the expressions of COL IV and laminin., Results: All of the low-grade dysplastic nodules were not hypervascular on CT arteriography, and negative for COL IV and laminin. All of the hepatocellular carcinomas were hypervascular on CT arteriography, and positive for COL IV and laminin. High-grade dysplastic nodules exhibit four hemodynamic patterns on CT during Arterial Portography/CT arteriography. All of 7 iso/iso and 5 iso/hypo nodules were negative for COL IV and laminin. Of the 9 hypo/hyper nodules, which exhibited hemodynamics similar to hepatocellular carcinoma, COL IV was identified in 7 and laminin identified in 8 nodules. Of the 3 hypo/hypo nodules, COL IV and laminin were identified in one., Conclusions: In high-grade dysplastic nodules, most cases exhibited a correlation between the hemodynamic patterns and the degree of the sinusoidal basement formation.

A 74-year-old man presented with hepatocellular carcinoma extending into the main portal vein. Two bare Wallstents were placed to maintain portal vein patency. The main portal vein remained patent for 6 months after treatment. No serious complications were observed during or after treatment.

The tumor-detecting capacity and clinical usefulness of superparamagnetic iron oxide (SPIO) magnetic resonance imaging (MRI) were examined in patients with hepatocellular carcinoma. The tumor detection rate of SPIO-MRI (64.5%) was comparable to those of dynamic computed tomography (CT) and plain MRI, but lower than that for Gd dynamic MRI (93.5%; P < 0.01%). A combination of Gd dynamic MRI and SPIO-MRI improved the detection rate; further, the tumor stage with respect to tumor blood-flow pattern was predicted by combining plain MRI with SPIO-MRI. This combination procedure may also be useful for selecting therapeutic strategies.

A case of an inflammatory pseudotumor of the liver in a 75-year-old female with chronic hepatitis C whose radiologic features simulated that of hepatocellular carcinoma (HCC) is presented. On imaging studies, hypervascularity by CO2 ultrasound (US) angiography, enhancement at an early phase and isodensity at a late phase by incremental dynamic computed tomography (CT), perfusion defect by CT during arteriography (CTAP), and clinical background of hepatitis C virus (HCV) infection strongly suggested HCC. A US-guided needle biopsy revealed a mainly diffuse and polyclonal proliferation of lymphocytes positive for leukocyte common antigen (pan-lymphocyte cells), L-26 (B cell lymphocytes), and UCHL-1 (T cell lymphocytes), negative for both kappa and lambda light chains and sparsely distributed neutrophils and histiocytes. No lymphoid follicles were observed. The liver tissue around this tumor showed chronic hepatitis with mild activity and mild fibrosis. These histopathologic findings suggested that the diagnosis of inflammatory pseudotumor of the liver was tenable. As it is difficult to differentiate between inflammatory pseudotumor of the liver and HCC by imaging studies alone, supplemental biopsy, where possible, should be obtained when diagnostic imaging of tumors suggesting HCC is carried out. We emphasize that histopathology is a true gold standard in the diagnosis of this disease.

A rare case of well-differentiated minute hepatocellular carcinoma (HCC) metastasizing to distant sites in a 77-year-old man with hepatitis C virus (HCV)-related cirrhosis is presented. Ultrasonography (US) disclosed a 9 mm hypoechoic lesion in segment seven (S7) of the liver, although computed tomography (CT), magnetic resonance imaging (MRI) and angiography did not reveal any space-occupying lesion. Ultrasound-guided biopsy showed the histological features of well-differentiated HCC. A plain film of the abdomen and CT revealed osteolytic changes in the sacrum and the lumbar vertebra. Ultrasound-guided biopsy of the sacrum revealed well-to-moderately differentiated HCC metastasizing from the liver. Percutaneous ethanol injection therapy (PEIT) effected complete response and completely eliminated the abnormal findings on US. Three months after PEIT, metastasis to the thoracic vertebra was revealed by CT, despite negative alpha-fetoprotein-mRNA in serum. This is the first report describing a well-differentiated HCC with metastatic potential. Further studies may provide insights into metastasis of well-differentiated HCC.

The purpose of this study was to evaluate a new oily agent in targeting chemoembilization for hepatocellular carcinoma. The oily preparation was made by mixing non-iodinated poppy seed oil and a thickener to obtain the same viscosity as Lipiodol. The oily preparation and Lipiodol were compared by injecting them into the hepatic artery of rabbits inoculated with VX 2 carcinoma in their liver. On the CT scan following intra-arterial injection, tumors were visibly stained in the non-iodinated preparation group, whereas the Lipiodol group was not evaluable because of excessively high attenuation. The non-iodinated oily preparation was concluded to be of clinical significance.

Selective segmental sclerotherapy of the liver by transportal ethanol injection (SSS) was devised and evaluated in a case of hepatocellular carcinoma. The patient was a 72-year-old man suffering from unresectable hepatoma. Injected ethanol with an amount of 20 ml into the portal branch under occluding the portal flow by balloon catheter produced complete necrosis of the liver proportional to the injected liver segment including the tumor on CT. Because of ethanol perfusion into sinusoid level by wedge injection, its cytotoxicity maybe affected liver cells directly. In this case, there has been no evidence of inadvertent liver damage and a significant rise in the blood ethanol level. The present technique of SSS in this clinical case and our past animal experience seemed to yield the same condition as resection without surgical disadvantages and be apparently a safe method, which is suggested for clinical use for several hepatic tumors.