Natural history of large regenerative nodules and dysplastic nodules in liver cirrhosis: 28-year follow-up study.

BACKGROUND AND AIMS: Some follow-up studies of large regenerative nodules (LRNs) and dysplastic nodules (DNs) were reported previously. However, the pre-malignant potentiality of LRNs has remained controversial up to now. No LRNs showed malignant transformation in our previous study. We aimed to evaluate the pre-malignant potentiality of LRNs and DNs with a greater number of cases and longer follow-up periods. METHODS: From 1982 to 2005, 1,500 consecutive nodular lesions up to 2 cm in diameter were subjected to US guided thin-needle biopsy in cirrhotic patients at Chiba University Hospital. Of these lesions, 68 LRNs in 60 cases and 20 DNs in 22 cases were followed up for more than 6 months without any anti-cancer therapy. The last US examination was in 2010. The total study period was 28 years. We analyzed the histological findings and the clinical data of all cases retrospectively. The outcome of the lesions was examined. RESULTS: The mean follow-up period was 38.9 (16-119) months in LRNs and 31.9 (6-101 months) in DNs. Rate of nodule enlargement was higher in DNs (8/24 nodules, 33%) than LRNs (11/68 nodules, 16 %), (p = 0.0743, not significant). Rate of malignant transformation was also higher in DNs (10/24 nodules, 42%) than LRNs (9/68 nodules, 13%), (p = 0.0040, significant). The rate of disappearance in images was similar between LRNs and DNs. CONCLUSIONS: We should recognize LRN as low risk pre-malignant lesions whereas DNs as high risk lesions.

[A case of duodenal gangliocytic paraganglioma with lymph node metastasis].

A 28-year-old man complained of tarry stool. A series of examinations showed a submucosal tumor with bleeding at the papilla of Vater and a swollen # 17b lymph node, both of which indicated a hypervascular tumor. The pathological findings of the enucleated tumor specimens revealed gangliocytic paraganglioma with metastasis to the # 17b lymph node. Additional pancreaticoduodenectomy revealed another # 17b lymph node metastasis 7-mm in diameter. Although the majority of gangliocytic paragangliomas are benign, 7% of reported cases have lymph node metastases, as shown in the present case. These findings are important in treating patients with gangliocytic paraganglioma.

A new approach for diagnosis of hepatolithiasis: magnetic resonance cholangiopancreatography: potential usefulness of dehydrocholic acid (DHCA) administration in the evaluation of hepatolithiasis.

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of hepatolithiasis. METHODOLOGY: Our study population comprised 9 patients. Magnetic resonance cholangiopancreatography (MRCP) was acquired before and after the administration of DHCA. Two different MRCP snap-shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. RESULTS: DHCA provided a better visualization of hepatolithiasis in 8 of 9 cases (88.9%). CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the hepatolithiasis on MRCP images.

Contrast-enhanced US with Levovist for the diagnosis of hepatic hemangioma: time-related changes of enhancement appearance and the hemodynamic background.

BACKGROUNDS/AIMS: To elucidate the diagnostic confidence of contrast-enhanced ultrasound (CEUS) with Levovist for hepatic hemangioma. METHODOLOGY: The subjects were 34 patients with 38 hemangiomas and 12 patients with 15 hypervascular hepatocellular carcinomas. The early-phase (15-60 second) and liver-specific phase (after 5 min) were observed by the first injection. The 2nd injection was done for solo-phase method to observe liver-specific phase images without taking early-phase sonograms. The 3rd injection was done for changing posture method to observe liver-specific sonograms under left lateral ducubitus position. RESULTS: In the early-phase of hemangioma, nodular enhancement (NE) was found transiently in 13 lesions (34%) and continuously in 25 lesions (66%), while hepatocellular carcinoma (HCC, n = 15) did not show this pattern. Intratumoral arterioportal shunt was closely related to the short duration of NE. Two enhancement patterns were observed in the liver-specific phase of hemangioma, diffuse in 12 lesions (31%) and partial in 26 lesions (69%), which were dependent on the early-phase enhancement. Liver-specific findings were also affected by taking early-phase sonograms or changing the posture of the patient. This method provided sensitivity of 79% and specificity of 100% for the diagnosis of hemangioma. CONCLUSIONS: CEUS with Levovist may be promising method for the diagnosis of hepatic hemangioma.

Magnetic resonance cholangiopancreatography: potential usefulness of dehydrocholic acid (DHCA) administration in the evaluation of biliary disease.

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of the biliary tree. METHODOLOGY: Our study population comprised 14 patients. Magnetic resonance cholangiopancreatography was acquired before and after the administration of DHCA. Two different MRCP snap shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. Volume rendering was prepared based on the source images, and the pixel size was visually adjusted to the biliary area of MRCP to measure the biliary tree volume. RESULTS: DHCA increased the bile duct volume in 13 of the 14 patients. It provided a better visualization of the biliary tree in 11 patients. The three patients without improvement in visualization included 1 patient with liver cirrhosis secondary to portoenterostomy for congenital biliary dilatation and 2 patients with cholecystectomy who had the bile ducts filled with bile by the time of the administration. CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the biliary tree on MRCP images.

Magnetic resonance cholangiopancreatography: potential usefulness of dehydrocholic acid (DHCA) administration in the evaluation of anastomotic site.

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of anastomotic site. METHODOLOGY: DHCA is a cholagogue which produces an immediate effect by acting directly on liver cells. Its choleretic effect is strong, appearing 1 to 3 minutes after intravenous injection, reaching the maximum level in 20 to 30 minutes. Our study population comprised 9 patients. Magnetic resonance cholangiopancreatography (MRCP) was acquired before and after the administration of DHCA. Two different MRCP snap-shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single-shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. RESULTS: DHCA provided a better visualization of the anastomotic site in 7 patients (77.8%). The two patients without improvement in visualization of anastomotic site included 1 patient with liver cirrhosis secondary to portoenterostomy for congenital biliary dilatation and 1 patient, who was not eligible for the evaluation because of motion artifact caused by the difficulty of breath holding motion artifact. CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the anastomotic site on MRCP images.

Diagnostic value of magnetic resonance cholangiopancreatography for clinically suspicious spontaneous passage of bile duct stones.

BACKGROUND AND AIM: We investigated the usefulness of magnetic resonance cholangiopancreatography (MRCP) and the need for endoscopic retrograde cholangiopancreatography (ERCP) in patients with clinically suspicious spontaneous passage of bile duct stones. METHODS: The study population consisted of 113 patients suspected of having common duct bile stones. Of them, 50 patients were clinically suspected of spontaneous passage of bile duct stones based on the presence of gallbladder stones on ultrasound examination or a history of common bile duct stones after cholecystectomy, clinical symptoms including abdominal pain and fever associated with inflammatory reaction and marked rise of hepatobiliary enzymes which resolved or normalized after conservative treatment without evidence of stones in the common bile duct on MRCP. These 50 patients were prospectively followed up for a median of 10.2 months. RESULTS: All patients except for one had had no symptoms related to cholangitis. Only one patient received ERCP due to recurrence of symptoms after 6 months. CONCLUSION: When clinical symptoms improve, hematological parameters normalize, and MRCP indicates that there are no stones in the common bile duct, it can be considered that the stones have passed naturally.

How to characterize non-hypervascular hepatic nodules on contrast-enhanced computed tomography in chronic liver disease: feasibility of contrast-enhanced ultrasound with a microbubble contrast agent.

BACKGROUND AND AIM: Although hypervascular appearance is characteristic in hepatocellular carcinoma (HCC), hepatic nodules without hypervascular appearance are sometimes found in patients with chronic liver disease (CLD). The aim of the present study was to clarify the efficacy of contrast-enhanced ultrasound (CEUS) with Levovist to characterize small, non-hypervascular hepatic nodules on contrast-enhanced computed tomography (CECT) in patients with CLD. METHODS: The subject was 41 hepatic nodules (<30 mm, 18.5 +/- 5.6 mm) which showed non-hypervascular appearance on CECT in 35 patients with CLD; their histological results were 31 HCC (15 well, 14 moderate, and two poor) and 10 regenerative nodules (RN). CEUS with Levovist was performed under intermittent scanning (1-s interval) using APLIO at the early phase and the liver-specific phase, and the contrast enhancement of the nodule was assessed in comparison to that of the surrounding liver parenchyma. The contrast-enhanced findings with the time-intensity analysis were compared with the histological results. RESULTS: Twelve nodules with weak enhancement in the liver-specific phase were HCC, regardless of their early-phase appearances. The other 29 nodules with equivalent or weak enhancement in the early phase and equivalent enhancement in the liver-specific phase were 19 HCC and 10 RN. Among them, the maximum-intensity ratio of tumor to non-tumor in the early phase was significantly higher in HCC than in RN (P < 0.01, n = 16), and the receiver-operating characteristic analysis showed a sensitivity of 1.0 and a specificity of 0.83 for their characterization. CONCLUSION: CEUS with Levovist may be an alternative to biopsy to characterize small, non-hypervascular hepatic nodules on CECT in patients with CLD.

Diagnostic value of MRCP and indications for ERCP.

BACKGROUND/AIMS: To assess the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) and examine the indications for endoscopic retrograde cholangiopancreatography (ERCP). METHODOLOGY: MRCP was performed in 185 patients with hepatobiliary disease in whom abdominal ultrasonography (US) had not been of diagnostic value. These patients were selected for MRCP in view of their abdominal symptoms, high levels of hepatobiliary enzymes, and pancreatic/bile duct dilatation found by abdominal US. Based on MRCP findings, 75 patients were selected for ERCP. RESULTS: ERCP provided new findings in 14 (18.%) patients. In 110 patients subjected to only MRCP and follow-up as well as in 75 patients with MRCP followed by ERCP, MRCP-based diagnosis corresponded with the final diagnosis. In our study, patients who would have conventionally required ERCP, such as those with natural passed choledocholithiasis and postoperative bile duct dilatation, could be followed up without ERCP. These results the importance of considering indications for ERCP. CONCLUSIONS: MRCP can be an alternative to ERCP at least for diagnosis.

Multidetector helical CT plus superparamagnetic iron oxide-enhanced MR imaging for focal hepatic lesions in cirrhotic liver: a comparison with multi-phase CT during hepatic arteriography.

The aim of this study was to evaluate multidetector helical computed tomography (MDCT), superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging, and CT arterial portography (CTAP) and CT during hepatic arteriography (CTHA) for the detection and diagnosis of hepatocellular carcinomas (HCC). This included visual correlations of MDCT and SPIO-MR imaging in the detection of HCC using receiver operating characteristic (ROC) analysis. Twenty-five patients with 57 nodular HCCs were retrospectively analyzed. A total of 200 segments, including 49 segments with 57 HCCs, were reviewed independently by three observers. Each observer read four sets of images (set 1, MDCT; set 2, unenhanced and SPIO-enhanced MR images; set 3, combined MDCT and SPIO-enhanced MR images; set 4, combined CTAP and CTHA). The mean Az values representing the diagnostic accuracy for HCCs of sets 1, 2, 3, and 4 were 0.777, 0.814, 0.849, and 0.911, respectively, and there was no significant difference between sets 3 and 4. The sensitivity of set 4 was significantly higher than those of set 3 for all the lesions and for lesions 10 mm or smaller (p<0.05); however, for lesions larger than 10mm, the sensitivities of the two sets were similar. No significant difference in positive predictive value and specificity was observed between set 3 and set 4. Combined MDCT and SPIO-enhanced MR imaging may obviate the need for more invasive CTAP and CTHA for the pre-therapeutic evaluation of patients with HCC more than 10mm.

Contrast-enhanced three-dimensional fusion sonography of small liver metastases with pathologic correlation.

PURPOSE: To demonstrate that liver metastases with a diameter of < or =40 mm show characteristic features on three-dimensional (3D) fusion sonographic images and that these sonographic findings can be correlated with histopathologic features of surgical specimens. METHODS: Liver metastases measuring < or =40 mm were examined via contrast-enhanced 3D fusion sonography. The characteristic sonographic findings of 17 tumor nodules in 11 patients with a histopathologically confirmed diagnosis of liver metastases were investigated, and their correspondence to the pathologic features were examined in 12 resected nodules. RESULTS: On sonograms, central vessels were visualized in all 17 tumor nodules and peripheral vessels were visualized in 12 nodules. On histopathologic examination, the portal triad vessels corresponded to the central vessels and were located at the center of the tumors. A thin layer of peritumoral hepatocytes showing various changes was also observed, and a group of tiny vessels were seen running along this layer of cells. CONCLUSIONS: Liver metastases measuring 40 mm or less in diameter were characterized by the presence of both central and peripheral vessels on contrast-enhanced 3D fusion sonography. There was good correlation between sonographic and histopathologic findings.

Microbubble disappearance-time is the appropriate timing for liver-specific imaging after injection of Levovist.

Contrast enhancement in the portal vein was repeatedly observed at 1 min intervals with wide-band Doppler ultrasonography in 152 consecutive patients (132 with liver cirrhosis and HCC, 20 controls), 5 min after the injection of Levovist. The duration time of contrast enhancement in the portal vein (microbubble disappearance-time; MD-T) was measured in all patients and contrast-enhanced appearances were compared between the 5 min phase and MD-T phase in 68 HCC nodules. MD-T in patients with liver cirrhosis (572.4 +/- 117.9 s) was significantly longer than in controls (481.6 +/- 89.3 s, p < 0.05). MD-T was prolonged in patients with Child B and C compared with Child A (p < 0.05). The contrast-enhanced appearances between the two phases were different in 30 of 68 HCC nodules (44.1%), showing positive enhancement in the 5 min phase and negative enhancement in the MD-T phase. The proposed MD-T may become an essential factor for the evaluation of liver-specific sonograms.

Recent applications of ultrasound: diagnosis and treatment of hepatocellular carcinoma.

Ultrasound (US) has the advantages of real-time observation, simple technique, and a noninvasive procedure compared to other imaging modalities. The recent development of digital technologies has enabled the observation of sonograms with improved signal-to-noise ratio, penetration, and spatial and contrast resolutions. Furthermore, microbubble contrast agents have increased the diagnostic ability of US examination, and the use of three-dimensional sonograms is now not unusual. These advances have furthered the usefulness of US for liver tumors in clinical practice. This article reviews the recent applications of US in the diagnosis and treatment of hepatocellular carcinoma.

Role of Clast1 in development of cerebellar granule cells.

We have identified the murine Clast1/LR8 gene by subtraction of cDNA derived from CD40 ligand-activated and naive B cells. The Clast1 gene is ubiquitously expressed in various organs of adult mice. However, its physiological function was largely unknown. To study a role of Clast1, we established Clast1-deficient (Clast1-KO) mice. Here, we reveal that approximately 65% of Clast1-KO mice showed severe ataxia. The Clast1-KO cerebellum with ataxia is small in size and revealed a severely aberrant lobulation, loss of the internal granule cell layer, and the disorganized Purkinje cells. Clast1 mRNA is expressed in the cerebellar granule cells of normal adult mice. Developmentally, Clast1 mRNA is also detected in the external germinal layer of the embryonic cerebellum, indicating its expression in granule cell precursors. Histopathological analysis of the developing Clast1-KO cerebellum demonstrated the reduced number of cells in the external germinal layer. Thus, Clast1 is required for development of cerebellar granule cells.

Ring-shaped appearance in liver-specific image with Levovist: a characteristic enhancement pattern for hypervascular benign nodule in the liver of heavy drinkers.

BACKGROUND/AIMS: The aim was to clarify the features of contrast-enhanced ultrasound (CEUS) with Levovist for diagnosis of hypervascular benign nodules in the liver of heavy drinkers. PATIENTS AND METHODS: Seven heavy drinkers with hypervascular nodules in the liver were studied. Findings of CEUS with Levovist (wide-band Doppler, 7/7), contrast-enhanced computed tomography (CECT, 7/7) and magnetic resonance imaging (MRI, 5/7) were compared for one nodule in each patient. RESULTS: Diagnosis of all seven nodules on CECT was HCC, whereas pathological results were HCC for four nodules and benign lesion for three nodules. The former four showed compatible findings for HCC on CEUS (4/4) and MRI (2/4). However, the latter three showed characteristic liver-specific sonograms with a ring-shaped appearance--peripheral enhancement with a central non-enhanced area. Two of the three nodules showed decreased signal-intensity in the periphery on SPIO-enhanced MRI. CONCLUSIONS: The ring-shaped appearance on liver-specific sonograms with Levovist may be a useful sign for the differential diagnosis of hypervascular benign nodule from HCC in heavy drinkers.

Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of P-glycoprotein and p53 protein in advanced hepatocellular carcinoma.

AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC). METHODS: The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the forty-one patients were treated with an anthracycline drug (epirubicin hydrochloride; anthracycline group), and the remaining 21 were treated with a non-anthracycline drug (mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group). The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS: Before the start of the treatment, PGP-positive rate was 90.2% (strongly-positive, 36.6%) and p53 protein-positive rate was 34.1% (strongly-positive, 19.5%). In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression (P=0.005), and their prognoses were poor (P=0.001). In the non-anthracycline group, the response rate was 42.9%, and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients (P=0.012), irrespective of the survival outcome. CONCLUSION: The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.

An improved diagnostic method for chronic hepatic disorder: analyses of metallothionein isoforms and trace metals in the liver of patients with hepatocellular carcinoma as determined by capillary zone electrophoresis and inductively coupled plasma-mass spectrometry.

It is desirable to diagnose hepatocellular carcinoma (HCC) in the early stages during its development since its treatment is usually difficult. We previously proposed a new diagnostic method that made use of the total metallothionein (MT), zinc (Zn), and copper (Cu) concentrations in the liver of the HCC patients. We recently found that MT-1 is involved in the metabolism or detoxification of toxic metals, such as cadmium; on the other hand, MT-2 is responsible for the homeostasis of essential metals such as copper, in experimental models such as Long Evans Cinnamon (LEC) rats. In order to device a better diagnostic method than the one we proposed previously, in this study, we newly propose an improved method that includes the discriminative determination data regarding the MT isomers, namely, MT-1 and MT-2, in the liver of patients with or without HCC as compared with the total MT level. The total MT and Zn concentrations in the HCC patients were confirmed to be significantly lower than those in patients without hepatic disorders (Ctrl). In contrast, Cu concentrations of the HCC patients were higher than those of the Ctrl patients. In addition, in the juxta-tumor portion with HCC, MT-1 concentrations were significantly higher than those of MT-2. In contrast, the MT-1 concentrations in the tumor portion were significantly lower than that in the juxta-tumor portion. In addition, MT-1/MT-2 ratio in the tumor portion was significantly lower than that of the juxta-tumor portion. By using parameters such as concentrations of Cu, Zn, total MT, and MT isomers, we performed the multivariate discriminative analysis (MDA). The results suggest that the concentrations of MT isomers change depending on the progress of the tumor, and information on MT isomers and trace elements is very useful in determining the stage of the chronic hepatic disorder.

A pilot approach for quantitative assessment of liver fibrosis using ultrasound: preliminary results in 79 cases.

BACKGROUND/AIMS: Ultrasound is noninvasive and useful to evaluate liver disease despite its operator dependency. This pilot study was conducted to quantitatively assess liver fibrosis using ultrasound. METHODS: Fibrosis extraction ratios (FER) (fiber volume/total volume) of ultrasound and histological images of 8 autopsy specimens were compared. We also compared FER of ultrasound images from clinical patients (n=79) with histological fibrosis stages. RESULTS: In the autopsy study, FER correlation coefficient between histological images and ultrasound images was 0.992. Regarding clinical patients, there was sufficient evidence to indicate differences in the distributions of FER for each fibrosis stage (Kruskal-Wallis test P<0.0001). With FER cut-off to distinguish > or =F2 from F0 and F1 defined as mean plus standard deviation of F0 and F1, sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were 62, 75, 78, 57%, and 2.47, respectively. Regarding HCV cohort (n=44), they were 55, 87, 89, 50%, and 4.14, respectively. Areas under receiver operating characteristic curves were 0.78, 0.79, 0.83 and 0.83 for > or =F1, > or =F2, > or =F3 and =F4, respectively. Regarding HCV cohort, they were 0.74, 0.71, 0.79 for > or =F2, > or =3 and =4, respectively. CONCLUSIONS: The FER method has great potential for diagnosing liver fibrosis using ultrasound.

Large regenerative nodule perfused by the portal vein.

In a 42-year-old Japanese woman with esophageal varices, abdominal ultrasound (US) demonstrated a hyperechoic lesion 3 cm in diameter in segment 4 (S4). This nodular lesion had high intensity on T1-weighted magnetic resonance imaging (MRI), low intensity on T2, and very high intensity on superparamagnetic iron oxide (SPIO) enhanced MRI. Angiography showed sparse distribution of arterial branches and dense distribution of portal branches in S4. Meandering, thin arteries were seen in the peripheral area of the right lobe. The second branches of the portal vein were hardly visualized anywhere in the liver. Computed tomography arterioportography (CTAP) revealed portal blood flow dominance in this nodular lesion. There was no evidence of ischemic liver damage, such as thromboembolic episodes, laboratory data of liver damage, coagulation abnormalities etc. Therefore this abnormality was more likely to be caused by anomalous changes than thrombotic changes. Needle biopsy revealed no atypical cells. Two years later, the nodule size was reduced to 1.9 cm, showing its benign nature. Based on these findings, this lesion was classified as a new type of large regenerative nodule (LRN) associated with anomalies in the portal veins and arteries. This is the first report of an LRN of this size in which portal vein perfusion was dominant. Moreover, this lesion was difficult to differentiate from hepatocellular carcinoma (HCC) by imaging. Analysis of the images and pathological features of this case would contribute to a better understanding of the pathogenesis of nodular lesions of the liver.

Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on 20-year observation.

BACKGROUND/AIMS: To evaluate the therapeutic efficacy of percutaneous ethanol injection (PEI) for patients with < or = 3 lesions of small (< or = 3 cm diameter) hepatocellular carcinoma (HCC). METHODS: PEI was applied to 270 patients with small HCC as the first-line treatment option during a 20-year period. RESULTS: (1) There was no treatment-related deaths, and only 2.2% of severe complications; (2) PEI induced a complete response of all HCCs according to CT evaluation performed within one month after the procedure, and the local recurrence rate at 3 years was 10%; (3) the overall 3- and 5-year survival rates after treatment were 81.6 and 60.3%, respectively, but the rates were higher, 87.3 and 78.3%, in Child A patients with a solitary tumor < or = 2 cm in diameter; (4) factors significantly influencing survival were liver function (P = 0.0033) and serum alpha-fetoprotein level (P = 0.0014), and (5) the recurrence rate at remote sites in the liver was lower in patients with HCC < or = 2 cm (P = 0.0395) and in those with a solitary HCC (P < 0.0001) according to Cox's proportional hazard model. (6) Radiofrequency ablation would not have been performed in approximately 25% of these patients. CONCLUSIONS: PEI is considered a reliable treatment for small HCC in terms of safety and efficacy.