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In the 18th Nationwide Follow-Up Survey of Primary Liver Cancer in Japan, 20 753 people were newly registered as patients with primary liver cancer at 544 medical institutions over a period of 2 years (from 1 January 2004 to 31 December 2005). Of these patients, 94.0% had hepatocellular carcinoma (HCC) and 4.4% had intrahepatic cholangiocarcinoma (ICC). In addition, 30 677 follow-up patients were registered in the survey. Epidemiological and clinicopathological factors, diagnosis and treatment were investigated in the newly registered patients. Compared with the 17th follow-up survey, this follow-up survey in HCC indicated an increase in elder patients and women, a decrease in patients positive for hepatitis B surface antigen and hepatitis C virus antibody, and a decrease in tumor size at the clinical diagnosis. In the local ablation therapy, ratio of radio frequency ablation therapy was increasing. The cumulative survival rates of newly-registered patients between 1994 and 2005 were calculated for each histological type (HCC, ICC, and combined HCC and ICC) and stratified by background factors and treatment. The cumulative survival rates of newly-registered patients between 1978 and 2005 divided into three groups (1978-1985, 1986-1995 and 1996-2005) were also calculated. The data obtained in this follow-up survey should contribute to future research and medical practice for primary liver cancer.

Background and aims Small hypovascular hepatocellular carcinoma (HCC) ≤2 cm is biologically less aggressive than hypervascular one, however, the optimal treatment is still undetermined. The efficacy of surgical resection (SR), radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) was evaluated. Methods The 853 (SR, 176; RFA, 491; PEI, 186) patients were enrolled who met Child-Pugh A/B, single hypovascular HCC ≤2 cm pathologically proven, available tumour differentiation and absence of macrovascular invasion and extrahepatic metastasis. Overall and recurrence-free survivals were compared in original and a propensity score weighted pseudo-population with 732 patients. Results The median follow-up time and tumour size were 2.8 years and 1.47 cm respectively. In original population, multivariate Cox regression showed no significant difference for overall survival among three groups. In pseudo-population, Cox regression also revealed no significant difference for overall survival among them, although SR (HR, 0.56; 95% CI, 0.36-0.86) and RFA (HR, 0.75; 95% CI, 0.57-1.00) groups had significantly lower recurrence than PEI group. The overall survival rates at 3 and 5 years for the SR, RFA and PEI groups were 94%/70%, 90%/75% and 94%/73% respectively. Corresponding recurrence-free survival rates were 64%/54%, 59%/41% 48%/33% respectively. Subgroup analysis revealed no significant survival benefit of SR compared with non-SR. No treatment-related death occurred. Conclusions For patients with single hypovascular HCC ≤2 cm, no significant difference for overall survival was first identified among 3 treatment groups. The SR or RFA could be recommended, and PEI would be alternative to RFA.

Transcatheter arterial chemoembolization (TACE) is widely performed in 32% of the patients with unresectable hepatocellular carcinoma (HCC) at initial diagnosis and in 58% of those with recurrent HCC in Japan. However, the patient population which undergoes TACE is heterogeneous, and thus the 3-year survival rate varies from 26 to 47%. The selection criteria for TACE is 2-3 tumors3 cm or 4 or more tumors in patients with liver damage A/B (corresponding well to Child-Pugh class A/B) and absence of vascular invasion and extrahepatic spread, as proposed by Japanese guidelines. The 3-year survival rate of TACE for patients with 2-3 tumors3 cm or 4 or more tumors was 55 and 46%, respectively, in Child-Pugh A and 30 and 22%, respectively, in class B. These outcomes could help to understand the various results of TACE in different backgrounds in the East and West. Recently, TACE with calibrated drug-eluting beads loaded with doxorubicin showed a similar tumor response and radioembolization with yttrium-90 microspheres demonstrated a similar median survival compared with conventional TACE. Based on these results, the combination of TACE and novel molecular targeted agents can be used to elucidate the synergic effect on survival.

In the 18th Nationwide Follow-Up Survey of Primary Liver Cancer in Japan, 20 753 people were newly registered as patients with primary liver cancer at 544 medical institutions over a period of 2 years (from 1 January 2004 to 31 December 2005). Of these patients, 94.0% had hepatocellular carcinoma (HCC) and 4.4% had intrahepatic cholangiocarcinoma (ICC). In addition, 30 677 follow-up patients were registered in the survey. Epidemiological and clinicopathological factors, diagnosis and treatment were investigated in the newly registered patients. Compared with the 17th follow-up survey, this follow-up survey in HCC indicated an increase in elder patients and women, a decrease in patients positive for hepatitis B surface antigen and hepatitis C virus antibody, and a decrease in tumor size at the clinical diagnosis. In the local ablation therapy, ratio of radio frequency ablation therapy was increasing. The cumulative survival rates of newly-registered patients between 1994 and 2005 were calculated for each histological type (HCC, ICC, and combined HCC and ICC) and stratified by background factors and treatment. The cumulative survival rates of newly-registered patients between 1978 and 2005 divided into three groups (1978–1985, 1986–1995 and 1996–2005) were also calculated. The data obtained in this follow-up survey should contribute to future research and medical practice for primary liver cancer.

The World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST) are inappropriate to assess the direct effects of treatment on the hepatocellular carcinoma (HCC) by locoreginal therapies such as radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Therefore, establishment of response evaluation criteria solely devoted for HCC is needed urgently in the clinical practice as well as in the clinical trials of HCC treatment, such as molecular targeted therapies, which cause necrosis of the tumor. Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2009 by Liver Cancer Study Group of Japan based on the 2004 version of RECICL, which was commonly used in Japan. Major revised points of the RECICL 2009 is to provide TE4a (Complete response with enough ablative margin) and TE4b (complete response without enough ablative margin) for local ablation therapy. Second revised point is that setting the timing at which the overall treatment effects are assessed. Third point is that emergence of new lesion in the liver is regarded as progressive disease, different from 2004 version. Finally, 3 tumor markers including alpha-fetoprotein (AFP) and AFP-L3 and des-gamma-carboxy protein (DCP) were also added for the overall treatment response. We hope this new treatment response criteria, RECICL, proposed by Liver Cancer Study Group of Japan will benefit the HCC treatment response evaluation in the setting of the daily clinical practice and clinical trials as well not only in Japan, but also internationally.

Although iodized oil transarterial chemoembolization (TACE) has been found to have survival benefit in the care of patients with unresectable hepatocellular carcinoma, iodized oil infusion chemotherapy without embolization has not been clearly found inferior to or equal to TACE. The purpose of this study was to determine whether one of these therapies is superior to the other or the two are equal in survival benefit and whether embolization with gelatin sponge particles is indispensable to prolonging survival.A prospective nonrandomized observational cohort study was conducted over 8 years. Among 11,030 patients with unresectable hepatocellular carcinoma, 8,507 underwent TACE, and 2,523 underwent transarterial infusion therapy with an emulsion of iodized oil and an anticancer agent as initial treatment. Patients with extrahepatic metastasis or any previous treatment were excluded. The primary end point was all-cause mortality. To minimize selection bias, propensity score analysis was used to compare the two groups.During the follow-up period, 5,044 patients (46%) died. In the analysis of all patients, TACE was associated with a significantly higher survival rate than infusion therapy without embolization (hazard ratio, 0.60; 95% CI, 0.56-0.64; p = 0.0001). The propensity score analysis showed that the hazard ratio for death in the TACE group (n = 1,699 patients) compared with the group who underwent infusion therapy without embolization (n = 1,699) was 0.70 (95% CI, 0.63-0.76; p = 0.0001). The median survival time of the TACE group was 2.74 years, and the 1-, 3-, and 5-year survival rates were 81%, 46%, and 25%. The corresponding values for the group who underwent transarterial infusion therapy without embolization were 1.98 years and 71%, 33%, and 16%.Propensity score analysis showed that in the treatment of patients with unresectable hepatocellular carcinoma, TACE was associated with significantly better overall survival rates than was transarterial infusion therapy without embolization. TACE can be recommended as initial treatment of these patients.

Of 15,681 patients with hepatocellular carcinoma (HCC), 30% underwent transcatheter arterial chemoembolization with lipiodol (Lip-TACE) including infusion chemotherapy with lipiodol (Lip-TAI) for the initial treatment, and 58% underwent it for recurrent HCC according to the latest biannual report of the Liver Cancer Study Group of Japan (LCSGJ). Superselective Lip-TACE is considered to be indispensable to maximize the therapeutic effect (TE) and to minimize injury to the non-cancerous liver. The local recurrence rate of a single session Lip-TACE for HCC ≤5 cm in diameter ranged from 33 to 38% at 3 years. A pathologic study using resected specimens of 26 HCCs treated by Lip-TACE showed that the mean necrosis rates and frequency of complete necrosis in three groups, small (≤3 cm, n = 6 HCCs), medium (3.1–5 cm, n = 10), and large size (≧5.1 cm, n = 10) were 95, 87.1%; 68.4, 66.7%; 30, 0%, respectively. Namely, the smaller the tumor size, the higher the TE. However, Lip-TAI showed no correlation between TEs and tumor size. A comparative study between the pathologically proven necrosis rate on the maximum cut surface of the lesion and radiologic necrosis estimated by CT showed a significantly good correlation when the lipiodol-retained area was presumed necrotic, but a poor correlation when it was presumed a viable one. No correlation was seen between the pathologic necrosis rate and the decreased rate of the lesion treated by Lip-TACE assessed by WHO criteria. The modified version of the assessment criteria of the TE of treatment for liver cancer was proposed by the LCSGJ in 2009, using a 4-grade treatment effect with two factors of tumor necrosis and tumor regression.

Although a surgical resection is an important modality for the treatment of hepatocellular carcinoma (HCC), the impact of the operative method on both the patient survival and disease-free survival (DFS) still remains controversial.Using a nationwide Japanese database, 72,744 patients with HCC who underwent a curative liver resection between 1994 and 2001 were divided into two groups based on whether an anatomical subsegmentectomy (AS) or a non-anatomical minor hepatectomy (MH) was performed. A total of 5,781 patients with single HCCs were selected for the study and divided into 3 subgroups based on the size of the HCCs (less than 2 cm, 2 to 5 cm, and greater than 5 cm in diameter). An AS was performed for 2,267 patients while an MH was performed for 3,514 patients.The overall DFS was significantly better after an AS (P = .0089). When the patients were stratified according to the size of the HCC, a better DFS was seen in the patients with HCC from 2 to 5 cm after an AS (P.0005). Further stratification according to liver damage did not show any significant differences between an AS and an MH.An AS is therefore recommended, especially when the size of HCC ranges from 2 to 5 cm.

In the 17th Nationwide Follow-up Survey of Primary Liver Cancer in Japan, 18 213 individuals were newly registered as patients with primary liver cancer at 645 medical institutions over a period of 2 years (from 1 January 2002 to 31 December 2003). Of these patients, 94.2% had hepatocellular carcinoma (HCC) and 4.1% had intrahepatic cholangiocarcinoma (ICC). In addition, 24 705 follow-up patients were registered in the survey. Epidemiological and clinicopathological factors, diagnosis and treatment were investigated in the newly registered patients, and the cumulative survival rates of newly registered patients in the 12th to 17th follow-up surveys conducted between 1992 and 2003 were calculated for each histological type (HCC, ICC, and combined HCC and ICC) and stratified by background factors and treatment. The data obtained in this follow-up survey should contribute to future research and medical practice for primary liver cancer.

Survival analysis in patients with initial recurrence after curative hepatectomy for hepatocellular carcinoma (HCC) has not been well evaluated. In addition, selections of the most effective treatments for patients with recurrent HCC still remain controversial.Three hundred and nineteen patients who underwent potentially curative hepatectomies were followed for initial recurrence, and factors predictive of recurrence were determined. The factors affecting survival including pattern of recurrence and treatment modalities from the time of initial recurrence in 211 patients were retrospectively analyzed.The overall 5-year disease-free survival rate of 319 patients was 31.1%. The 5-year survival rate of 211 patients from the time of initial recurrence was 31.9%. In a multivariate analysis, a low indocyanine green retention rate, lack of liver cirrhosis, a long interval before recurrence, the absence of portal vein invasion, and intrahepatic recurrence (or=3 nodules) were shown to be significantly favorable prognostic factors after the initial recurrence. The 5-year survival rate of patients with intrahepatic recurrence (or=3 nodules) was 42.3%, and no survival differences were observed among different treatment modalities.When the initial recurrence occurred after a longer interval, and/or with three or fewer intrahepatic recurrent nodules, a favorable prognosis could be expected in those patients with better liver function and no portal vein invasion at the time of the primary hepatectomy. It is important to conduct a randomized controlled trial to clarify a method for selecting optimal treatment in patients with a smaller number of initial intrahepatic recurrences.

The purpose of this study was to clarify the natural outcomes of hypoattenuating nodular lesions in patients with virus-related chronic liver disease depicted on dynamic CT.Sixty lesions (mean size, 1.3 cm) exhibiting hypoattenuation or isoattenuation in the arterial and delayed phases of dynamic CT were retrospectively evaluated with additional CT (mean, six examinations) for a mean period of 838 days. The primary end point was emergence of hyperattenuating areas within hypoattenuating lesions, a phenomenon called attenuation conversion. Cumulative attenuation conversion rates suggesting rates of malignant transformation were calculated with the Kaplan-Meier method, and factors affecting attenuation conversion rate were analyzed with the Cox proportional hazard model.Thirty-six (60%) of 60 hypoattenuating lesions developed to hyperattenuating lesions, 21 were unchanged, and three disappeared spontaneously. The 36 lesions that became hyperattenuating were divided into two subgroups according to lesion enhancement pattern: hyper-in-hypoattenuating (n = 25) and entirely hyperattenuating (n = 11). The cumulative attenuation conversion rates for the 60 hypoattenuating lesions were 15.8%, 44.3%, and 58.7% at 1, 2, and 3 years. The hyper-in-hypoattenuating lesions showed more rapid progression to entirely enhanced lesions. Positive results for hepatitis C viral antibody (p = 0.028) and initial lesion size (p = 0.007) showed a positive correlation with attenuation conversion rate.Hypoattenuating hepatic nodular lesions in chronic liver disease depicted on dynamic CT have high malignant potential and should be followed with special attention to conversion from hypoattenuation to hyperattenuation to determine the optimal timing of treatment.

In the 16th nationwide follow-up survey of primary liver cancer, 19,920 patients were newly registered as patients with primary liver cancer at 795 medical institutions in Japan over a period of 2 years (from January 1, 2000 to December 31, 2001). Of these patients, 94.5% had hepatocellular carcinoma (HCC) and 3.6% had intrahepatic cholangiocarcinoma (ICC). In addition, 21,268 follow-up patients were registered, and a valid response rate of 75.6% was obtained in these follow-up patients. In this study, epidemiological and clinicopathological factors, diagnosis and treatment were investigated in patients who were newly registered in the 16th follow-up survey. As additional statistics, the cumulative survival rates of newly registered patients in the 11th to 16th follow-up surveys were calculated for each histological type (HCC, ICC and combined HCC and ICC) by background factor(s) and treatment, respectively. Furthermore, in patients with HCC, the cumulative survival rates were calculated for several types of treatment (hepatectomy, local ablation therapy and transcatheter arterial chemoembolization). It is anticipated that this follow-up survey will contribute to future research and medical practice for primary liver cancer.

Aim: To study the clinicopathologic characteristics of hepatic nodular lesions with high attenuation (increased portal blood flow) compared with surrounding hepatic parenchyma on computed tomography (CT) during arterial portography (CTAP). Methods : For six lesions found in six patients demonstrated as a high-attenuated mass by CTAP, CT during hepatic arteriography (CTHA; n = 3 patients), digital subtraction hepatic arteriography (n = 6) and conventional helical CT (n = 6) were evaluated retrospectively and compared with histopathologic findings (n = 4). Pathologic diagnosis was atypical adenomatous hyperplasia, nodule-in-nodule hepatocellular carcinoma (HCC) in one resected lesion each and overt HCC in two biopsied lesions. Two patients did not undergo any therapy and were followed up. Results : The average size of lesions was 2.2 cm (range 1.2–3.5 cm). The CTAP revealed high attenuation in all six lesions; entirely within the lesion (n = 4 lesions) or peripherally with a central low attenuation (n = 2). In contrast, CTHA showed low attenuated lesions; entirely within the mass (n = 2) or peripherally with a central high-attenuated spot (n = 1). Hepatic arteriogram revealed only two hypervascular lesions; entirely and partially in one each. In the arterial phase of helical CT, all but one lesion were iso- or hypo-attenuated. In two patients who were followed up to 39 and 55 months without therapy, neither tumor growth nor hemodynamic change of the lesion was recognized on CT. Conclusions: Even though the incidence of hepatic nodular lesions demonstrated as high attenuating on CTAP is low, all but one lesion in the current series showed iso- or hypo-attenuation on CTHA and/or helical CT, suggesting the hemodynamics are reciprocal between CTAP and CTHA. One exceptional lesion that showed high attenuation on both CTAP and conventional CT was pathologically advanced HCC. Based on the follow-up study of two untreated patients, this kind of lesion with high attenuation on CTAP seems to grow slowly. © 2002 Blackwell Publishing Asia Pty Ltd

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). In our previous study, transcatheter arterial infusion chemotherapy using SMANCS for HCC showed a response rate of 20%. In an effort to obtain a superior anti-tumor effect against HCC, we conducted a phase II study of transcatheter arterial embolization (TAE) using SMANCS and gelatin sponge in 50 chemotherapy-naive patients with HCC. Four milligrams SMANCS plus 4 ml lipiodol emulsion was injected into the hepatic artery, followed by an injection of gelatin sponge. The responses were evaluated by computed tomography (CT) 1 month after treatment and thereafter every 3–4 months. One patient (2%) showed complete response and 15 patients (30%) had partial response resulting in an overall response rate of 32% (16/50; 95% confidence interval 19–45%). In 33 patients (66%), the disease remained stable, and 1 patient (2%) showed progressive disease. In 35 patients (70%), the rate of necrotic area to whole tumor was more than 50% according to the evaluation method using lipiodol accumulation in CT. The 1-, 3- and 5-year survival rates were 90, 55 and 19%, respectively. Grade 3 hematological toxicity was observed as thrombocytopenia in 2 patients (4%). Grade 3 and 4 non-hematological toxicity (liver dysfunction) occurred in 17 (34%) and 7 patients (14%), respectively. TAE using SMANCS, which was well tolerated, may be an effective treatment for advanced HCC.

Aims: To evaluate haemodynamic and vascular changes in non-alcoholic (viral) cirrhosis on conventional computed tomography (CT), CT arteriography (CTA) and CT arterial portography (CTAP), and to determine the cause of the observed reticular stain on angiography. Methods: Using surgically resected liver specimens from 31 patients with viral hepatitis associated hepatocellular carcinoma, images of conventional CT, CTA, CTAP and the sinusoidal phase of hepatic arteriography were retrospectively analysed and compared with pathology of the non-cancerous portion of the liver. Results: Computed tomography arteriography showed inhomogeneous enhancement (diffuse, low-density nodules) in a total of 16 samples (52%); in eight of 10 (80%) cirrhotic livers, three of six (50%) precirrhotic livers, five of 12 (42%) livers with chronic active hepatitis and none of three with no active liver disease. The frequency of inhomogeneous enhancement became significantly higher with increasing severity of parenchymal damage (P < 0.05). In contrast, conventional CT and CTAP showed homogeneous enhancement in all 31 (100%) patients. There was no correlation between inhomogeneous enhancement on CTA and reticular staining on sinusoidal-phase hepatic angiograms. Inhomogeneous enhancement was frequently seen in patients with hepatitis B surface antigen and/or anti-hepatitis C virus antibody compared with those without them (P < 0.05). Conclusion: The CTA was much more sensitive in detecting haemodynamic changes in the cirrhotic liver than CTAP, conventional CT and sinusoidal-phased hepatic angiography. Further study is required to clarify the mechanism of inhomogeneous enhancement on CTA and homogeneous enhancement on CTAP seen in cirrhosis.

Early hepatocellular carcinoma (HCC) has been defined as a well-differentiated cancer containing Glisson's triad, but it remains unknown whether this lesion is curable. We prospectively studied 70 patients (enrolled from 1,172 referrals between 1982 and 1991) who had a diagnosis of a single HCC 2 cm or less in diameter (Stage T1) and who underwent curative hepatectomy and long-term follow-up (range, 0.2 to 14.3 years). Patients were eligible for surgery if they had a tumor that met the diagnostic criteria for HCC and were in Child-Pugh class A (n = 59) or B (n = 11) status. Among the 70 patients, there was 1 operative death. Based on our typing system, the tumors were assigned as early HCC (n = 15), overt HCC (n = 52), and non-HCC tumor (n = 3). The rate of microscopic regional spread was lower in early HCCs than in overt HCCs (7% vs. 42%; P = .01). The early HCC group had a longer time to recurrence than did the overt HCC group (3.9 vs. 1.7 years; P < .001) and had no local recurrence. After a median follow-up of 6.3 years, both overall survival and recurrence-free survival in the early HCC group were significantly better than those in the overt HCC group (P = .01; P = .001). In these two groups, the 5-year rates of overall survival were 93% and 54% (P = .01), and those of recurrence-free survival were 47% and 16% (P = .05), respectively; a significant survival benefit persisted over a decade (57% vs. 21%; P = .05). The early HCC group was at a lower risk of recurrence (relative risk, 0.31; 95% CI, 0.15 to 0.65; P = .002) and death (relative risk, 0.26; 95% CI, 0.09 to 0.73; P = .01) than was the overt HCC group. Early HCC is a distinct clinical entity with a high rate of surgical cure, thereby justifying its definition. It can be a lesion that corresponds to "Stage 0" cancer in other organs.

A 5-cm pheochromocytoma located in segment 7 of the liver was found incidentally in a 45-year-old man with mild diabetes mellitus and hypertension, and resected. The tumor was demonstrated by computed tomography and magnetic resonance imaging to have completely invaginated itself into the liver and to be receiving blood from a dilated right hepatic artery alone. Surgery revealed the hepatic mass to be tightly adherent to the right adrenal gland. The histopathologic diagnosis was pheochromocytoma growing exophytically from the right adrenal gland. There was no association with multiple endocrine neoplasia type 1 and type 2. A postoperative 131I metaiodobenzylguanidine scan revealed no accumulation, and the patient is currently doing well without recurrence or hypertension one year after the operation. A pheochromocytoma deeply invaginating into the liver should be considered in the differential diagnosis of primary hypervascular hepatic tumors.

PURPOSE: To clarify the diagnostic importance of wedge-shaped areas of increased signal intensity that surround liver tumors on T1-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: In five patients with hepatic tumors, T1-weighted MR images that demonstrated wedge-shaped areas of increased signal intensity in the liver were reviewed; findings were compared with those at surgical and histologic examinations. RESULTS: MR images showed localized intrahepatic bile duct dilatation lateral (three patients) and medial (two patients) to liver tumors within the wedge-shaped areas. At histopathologic examination, intraductal tumor growth was seen in local bile ducts in the same areas in five patients, and lipofuscin deposits were seen in the cytoplasm of atrophic hepatocytes in three patients. CONCLUSION: On T1-weighted images, wedge-shaped areas of increased signal intensity associated with liver tumors indicate intraductal tumor extension in intrahepatic bile ducts. T1 shortening is possibly caused by lipofuscin deposits in atrophic hepatocytes.

For two patients with partial Budd‐Chiari syndrome secondary to hepatocellular carcinoma, dynamic CT was evaluated. The obstructed hepatic veins were both the middle and left hepatic veins in Case 1 and the right hepatic vein in Case 2. The area affected by obstructed hepatic vein(s) was seen as low density on both unenhanced and contrast enhanced CT in Case 1 and as high density on enhanced CT in Case 2. The border of attenuation differences caused by the obstruction of the middle (Case 1) or right (Case 2) hepatic vein was intersegmental planes of the anterior segment of the right lobe, and that caused by the obstruction of the left hepatic vein was the intersegmental plane of the medial third of the left lateral segment. Once intersegmental attenuation difference is recognized on CT, partial Budd‐Chiari syndrome should be considered.

The existence of excrescent nodules in the cystic component of intraductal papillary neoplasms (IPN) on computed tomography (CT) is useful for differentiating between malignant and benign lesions We sought to evaluate the ability of CT to differentiate malignant from benign lesions in IPN of the pancreas. CT findings in 20 cases of IPN (11 benign and 9 malignant lesions) were compared with histopathological findings from subsequent surgery. The size of the cystic protion on CT did not correlate with the malignant potential of the lesion. Seven (78%) of 9 malignant lesions had excrescent nodules on CT, whereas 1 (9%) of 11 benign lesions did.

Transcatheter arterial chemoembolization (TACE) is widely performed in 32% of patients with unresectable hepatocellular carcinoma (HCC) at initial diagnosis and in 58% of those with recurrent HCC in Japan. However, the patient population which undergoes TACE is heterogeneous, and thus the 3-year survival rate varies from 26 to 47%. The selection criteria for TACE is 2-3 tumors >3 cm or 4 or more tumors in patients with liver damage A/B (corresponding well to Child-Pugh class A/B) and absence of vascular invasion and extrahepatic spread, as proposed by Japanese guidelines. The 3-year survival rate of TACE for patients with 2-3 tumors >3 cm or 4 or more tumors was 55 and 46%, respectively, in Child-Pugh A and 30 and 22%, respectively, in class B. These outcomes could help in understanding the various results of TACE in different backgrounds in the East and West. Recently, TACE with calibrated drug-eluting beads loaded with doxorubicin showed a similar tumor response and radioembolization with yttrium-90 microspheres demonstrated a similar median survival compared with conventional TACE. Based on these results, the combination of TACE and novel molecular targeted agents can be used to elucidate the synergic effect on survival.

Objective: To clarfy imaging and clinicopathologic features of lymphoepithelial cysts (LEC), a benign lesion of the pancreas. Materials and Methods: Two male patients with LECs that were found incidentally and proven surgically were reviewed. Results: Sonography revealed a hypoechoic mass in both cases, one of which had septation and an intracystic isoechoic component within it. The mass was shown as low attenuation on unenhanced CT, and the intracystic solid component was not enhanced by dynamic CT or computed tomographic arteriography. One lesion had calcifications around the mass. Magnetic resonance imaging showed hyper- in hypointensity on T1-weighted imaging and hypo- in hyper- on T2-weighted imaging in one case. Both lesions were located on the surface of the head of the pancreas, and the main pancreatic ducts appeared normal on endoscopic retrograde pancreatography. Both patients were asymptomatic. Conclusion: These imaging and clinical findings suggest LEC, which should be considered when one encounters cystic lesions of the pancreas

A 64-year-old man who underwent hepatectomy for hepatocellular carcinoma (HCC) 4 years ago followed by transarterial chemoembolization for recurrent foci 1 year later had a thrombus in the inferior vena cava (IVC). Tumor thrombus derived from HCC was suspected owing to the increase in size and hepatic arteriography was performed. Common hepatic arteriography demonstrated a small stain suggesting a recurrent HCC in the remnant liver. However, CT during hepatic arteriography revealed that the stain localized not in the liver but within the thrombus in the IVC; there was no recurrent HCC in the liver. The dense stain associated with thin neovasculature developed through the thrombus was recognized. The thrombus spontaneously regressed 8 months later. It was speculated that the neovasculature played an important role in a process of absorption of the thrombus. One should note that the stain shown on angiography does not always suggest that the lesion is localized in the liver and is malignant.

Background & Aims To clarify the biological behaviour of small hypovascular hepatocellular carcinoma (HCC) because of insufficient evidence even though frequently encountered. Methods The study covered naive 4,474 patients who met solitary HCC ≤3 cm (mean, 2.1 cm), histopathologically proven and Child Pugh A or B. Macroscopic vascular invasion and distant metastasis were excluded. The hypovascularity of tumour was defined as hypo- or iso-enhancement in arterial phase of multiple dynamic imaging techniques. Results Of them, 802 (18%) were hypovascular. The ratio of hypovascular HCC decreased as tumour size increased (P

Transcatheter arterial chemoembolization has been performed worldwide for patients with unresectable hepatocellular carcinoma for three decades. After long controversy, survival benefit was revealed by two randomized controlled trials. In Japan, chemoembolization accounted for initial treatment of 32% of patients and 58% for recurrent foci. The indications of chemoembolization are various: they are multinodular tumors in the Barcelona Clinic Liver Cancer staging system and two or three tumors >3 cm or four or more tumors in the Japanese guidelines, and both indications fulfill the Child-Pugh Class A/B or liver damage A/B and exclusion of vascular invasion or extrahepatic spread. Recently, both guidelines were identified to have almost similar content. The 4966 patients stratified to chemoembolization recommended by the Japanese guidelines showed that 3-year survival of patients with two or three tumors >3 cm or four or more tumors was 55 and 46% in Child-Pugh A, respectively, and 30 and 22% in Class B, respectively. These results would help in comparing the outcome of chemoembolization in the different backgrounds of the East and West. The modified Response Evaluation Criteria in Solid Tumor guideline is now proposed to cover the deficiency of Response Evaluation Criteria in Solid Tumor to evaluate the response to chemoembolization. Recently, chemoembolization with drug-eluting beads and radioembolization with yttrium-90 microspheres have been introduced, and each of them showed similar tumor response and median survival compared with conventional chemoembolization. Moreover, the combination of chemoembolization and molecular targeted agent is now on-going to evaluate the synergistic effect.

A randomized controlled clinical trial was conducted to compare the use of Farmorubicin (FARM) and Adriamycin (ADR) in Lipiodol transcatheter arterial chemoembolization (L-TAE) as a treatment of hepatocellular carcinoma. In all, 192 hospitals participated, and 415 patients were enrolled in the study during the period from October 1989 through December 1990, and their data were collected. The patients were randomly allocated to group A (FARM) or group B (ADR) by a central telephone registration. Several clinical characteristics were slightly worse in group A than in group B, but there was no statistically significant difference. The actual doses of FARM and ADR were 72 mg/body and 48 mg/body, respectively. Additional treatments, including repeated TAE or surgery, were given to 248 patients. The 1- and 2-year survival rates were 69% and 44% for group A and 74% and 57% for group B, respectively. The difference was marginally significant (P value in the log-rank test, 0.038). When each group of patients was classified into two subgroups, i.e., high-risk and low-risk categories, based on the severity index calculated by the Cox regression model from significant prognostic factors, the ADR subgroup was significantly superior to the FARM subgroup in the low-risk category, but there was no significant difference between the subgroups in the high-risk category. The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction did not show any significant difference between the groups. At the above-mentioned doses, ADR seemed to have efficacy almost the same as or slightly superior to that of FARM in L-TAE for the treatment of hepatocellular carcinoma.

Background & Aims Transcatheter arterial chemoembolization with lipiodol (TACE) is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. It has recently been recommended for patients with 2 or 3 tumors >3cm or ⩾4 tumors in a treatment algorithm proposed by Japanese guidelines. However, the best indication and appropriateness of the algorithm for TACE are still unclear. Methods In 4966 HCC patients who underwent TACE, survival was evaluated based on tumor number, size and liver function; and the adequacy of the algorithm for TACE was validated. Exclusion criteria were: vascular invasion, extrahepatic metastasis, and prior treatment. The mean follow up period was 1.6years. Results The overall median and 5-year survivals were 3.3years and 34%, respectively. Multivariate analysis revealed that Child–Pugh class, tumor number, size, alpha-fetoprotein, and des-gamma carboxy-prothrombin were independent predictors. The survival rate decreased as the tumor number ( p =0.0001) and size increased ( p =0.04 to p =0.0001) in all but one subgroup in both Child–Pugh-A and -B. The stratification of these patients to four treatments in the algorithm showed potential ability to discriminate survivals of the resection and ablation (non-TACE) groups from those of the TACE group in Child–Pugh-B and partially in A. Conclusions TACE showed higher survival rates in patients with fewer tumor numbers, smaller tumor size, and better liver function. The treatment algorithm proposed by the Japanese guidelines might be appropriate to discriminate the survival of patients with non-TACE from TACE therapy.

Clinicoradiological features were studied in 20 patients with 22 mass lesions of combined hepatocellular carcinoma and cholangiocarcinomas and findings of computed tomography in 12 of these patients with 14 hepatocellular carcinoma-cholangiocarcinomas. Five of these patients also had single overt hepatocellular carcinomas. The incidence of hepatocellular carcinoma-cholangiocarcinoma was 3.3% among the patients with primary liver cancer treated in our hospital. HBsAg was present in 25%, and increased levels of serum alpha-fetoprotein (> 200 ng/ml) and carcinoembryonic antigen (> 5 ng/ml) were found in 25% and in 47%, respectively. Associated cirrhosis was present in 60%. Analysis of 14 hepatocellular carcinoma-cholangiocarcinomas in 12 patients in whom the enhancement pattern on dynamic computed tomography and pathological findings could be studied and compared suggested three tumor types. Nine lesions (type A) were demonstrated only as areas with high-density peripheries in the early phase of enhancement that evolved into a pattern of peripheral low density and central high density in the late phase. Four masses (type B) were shown as hyperdense tumors (early phase) that changed to low density in the late phase. One mass (type C) was seen as a low-density lesion that did not change. Histopathologically, type A comprised hepatocellular carcinoma-predominant components in the peripheral area, cholangiocarcinoma-predominant components with abundant fibrous stroma in the central area and a tissue transitional between the two in the midzone. By contrast, two of four type B masses comprised hepatocellular carcinoma with scattered cholangiocarcinoma components throughout the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatocellular carcinomas frequently occur in association with liver cirrhosis, as chronic liver disease is one of the most important factors in carcinogenesis. In addition to small hepatocellular carcinomas (less than 3 cm in diameter), recent reports of pathologic studies of resected specimens from cirrhotic liver describe associated small nodular lesions (i.e., regenerating nodule, adenomatous hyperplasia, and early hepatocellular carcinoma). In hepatocarcinogenesis of the cirrhotic liver, a regenerating nodule might be the first step in the development of hepatocellular carcinoma, going through phases of adenomatous hyperplasia and early hepatocellular carcinoma in a multistep fashion. We describe the pathologic characteristics of small hepatocellular carcinomas and associated nodular hepatic lesions and review the current concepts of the role of these associated lesions in carcinogenesis. We also discuss the imaging findings of these abnormalities, the efficacy of various imaging techniques for diagnosing them, and the importance of imaging in treatment planning.

Background High recurrence rates after liver resection with curative intent for hepatocellular carcinoma (HCC) remain a problem. The characterization of long-term survivors without recurrence after liver resection may help improve the therapeutic strategy for HCC. Methods A nationwide Japanese database was used to analyse 20 811 patients with HCC who underwent liver resection with curative intent. Results The 10-year recurrence-free survival rate after liver resection for HCC with curative intent was 22·4 per cent. Some 281 patients were recurrence-free after more than 10 years. The HCCs measured less than 5 cm in 83·2 per cent, a single lesion was present in 91·7 per cent, and a simple nodular macroscopic appearance was found in 73·3 per cent of these patients; histologically, most HCCs showed no vascular invasion or intrahepatic metastases. Multivariable analysis revealed tumour differentiation as the strongest predictor of death from recurrent HCC within 5 years. Conclusion Long-term recurrence-free survival is possible after liver resection for HCC, particularly in patients with a single lesion measuring less than 5 cm with a simple nodular appearance and low tumour marker levels.

The World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST) are inappropriate to assess the direct effects of treatment on the hepatocellular carcinoma (HCC) by locoreginal therapies such as radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Therefore, establishment of response evaluation criteria solely devoted for HCC is needed urgently in the clinical practice as well as in the clinical trials of HCC treatment, such as molecular targeted therapies, which cause necrosis of the tumor. Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2009 by Liver Cancer Study Group of Japan based on the 2004 version of RECICL, which was commonly used in Japan. Major revised points of the RECICL 2009 is to provide TE4a (Complete response with enough ablative margin) and TE4b (complete response without enough ablative margin) for local ablation therapy. Second revised point is that setting the timing at which the overall treatment effects are assessed. Third point is that emergence of new lesion in the liver is regarded as progressive disease, different from 2004 version. Finally, 3 tumor markers including alpha-fetoprotein (AFP) and AFP-L3 and des-gamma-carboxy protein (DCP) were also added for the overall treatment response. We hope this new treatment response criteria, RECICL, proposed by Liver Cancer Study Group of Japan will benefit the HCC treatment response evaluation in the setting of the daily clinical practice and clinical trials as well not only in Japan, but also internationally.

To differentiate focal nodular hyperplasia (FNH) from other hepatic tumors, especially hepatocellular carcinoma, we evaluated the hemodynamics of histologically proved FNH in three patients, two by arterial angio-CT and one by microangiography of the resected specimen. These studies demonstrated the centrifugal blood supply of FNH (early filling of central tumor vessels radiating to periphery, and lobulated tumor stains with central low density area in the late phase), which could not be demonstrated by dynamic CT or hepatic angiography. Arterial angio-CT is useful as a further study, when differential diagnosis of FNH is uncertain by other imaging techniques.

A randomized clinical trial comparing L-TAE with Farmorubicin (FARM) and L-TAE with Adriamycin (ADR) in the treatment of hepatocellular carcinoma was conducted from October 1989 through December 1990. In all, 192 hospitals participated in this study and 117 patients were entered. The patients were randomly allocated to group A (L-TAE+FARM) or group B (L-TAE+ADR). There was no significant intergroup difference in background factors. Additional treatment consisting of repeated TAE or surgery was given to 66 patients. Four factors were analyzed in this study: the percentage of reduction in tumor size, the change in the AFP level, lipiodol accumulation, and survival. None of these factors differed significantly between the two groups. The final evaluation of this study will be based on differences in survival after a long-term follow-up. Toxic effects manifested less frequently in group A than in group B, and the decrease in the platelet count in the peripheral blood was significantly lower in group A than in group B. These results suggest that FARM exerts a more favorable effect than does ADR in the treatment of hepatocellular carcinoma.

During follow-up of non-Hodgkin lymphoma in a 60-year-old man, multiple hepatic small lesions were incidentally found by sonography. Dynamic CT disclosed enhancing masses in both the right and left lobes and faint arterioportal shunting in the left lobe of the liver. These findings were confirmed by angiography. Portal hypertension was, however, not present. Exploratory laparotomy revealed nodular regenerative hyperplasia of the liver. The nontumorous liver was normal.

Background/Aims The treatment of choice for HCC remains controversial. We evaluated the therapeutic impact of surgical resection, PEI, and RFA for HCC on outcomes. Methods A database derived from a Japanese nationwide survey of 17,149 patients with HCC treated by resection, PEI, or RFA between 2000 and 2003 was used to identify 7185 patients with no more than 3 tumors (⩽3cm) and a liver function of Child-Pugh class A or B. The patients classified into either a resection ( n =2857), RFA ( n =3022), or PEI group ( n =1306) and their long-term outcomes were compared. Results The median follow-up period was 10.4months. The 2-year time-to-recurrence rate was 35.5%, 55.4%, and 73.3% in the resection, RFA, and PEI groups, respectively, while the number of recurrences was 2410, 2368, and 862. Although the number of deaths was 55 (1.9%), 49 (1.6%), and 39 (3.0%), the overall survival rates were not different. In a multivariate analysis, surgical resection was a significant negative factor for recurrence as compared with RFA (relative risk, 0.62 [95% confidence interval, 0.54–0.71], P P Conclusions This preliminary report suggested that surgical resection may provide less time-to-recurrence rate than either RFA or PEI in patients with HCC.

近年の腹部超音波検査, computed tomography, 経皮経肝門脈造影など診断技術, 機器の発達により肝内の脈管構築の把握がより容易になってきている. 今回われわれは画像診断で異常な肝内門脈走行を示したl Trlを経験した. 症例は肝腫場にて精査中門脈右前枝の裏状の拡張, 門脈左枝踏部の欠損, 肝円索の位置異常を認めた. このような肝内門脈の異常走行例はごくわずかで (0.1%) その原因は胎児期の発生異常と考えられた. 画像診断による肝内の脈管構築の把握は肝切除術特に脈管処理に際して重要である.

Background: The Liver Cancer Study Group of Japan has designated early hepatocellular carcinoma (HCC) a clinically early-stage HCC corresponding to a high-grade dysplastic nodule as proposed by the International Working Party. Methods: The majority of resected early HCCs were demonstrated as having hypo- or isoattenuation in the arterial and delayed phases of dynamic CT. Results: Only 5% of early HCCs were hyperattenuated on dynamic CT, whereas 94% of advanced small HCC were hyperattenuated. CT arterial portography (CTAP) showed that 66% of early HCCs were hypo- and 34% were isoattenuated. CT hepatic arteriography (CTHA) demonstrated that 55% of them were hypo-, 30% were iso- and the remaining 15% were hyperattenuated. Conclusions: These findings suggest that most early HCCs receive equal or decreased blood supply from both portal and arterial blood flow compared with surrounding hepatic parenchyma. In contrast, 97% of small advanced HCCs were hypoattenuated on CTAP, and 93% were hyperattenuated on CTHA. For nodule-in-nodule type HCC, the central portion of the lesion was hyperattenuating and the peripheral portion was hypoattenuating in the arterial phase of dynamic CT, and both areas became hypoattenuated in the delayed phase. Sixty hypoattenuating nodular lesions in chronic liver disease were followed periodically with helical CT. Thirty-six (60%) of them developed to the hyperattenuating type (attenuation conversion), 21 were unchanged, and 3 disappeared spontaneously. The hyper-in-hypo-attenuating lesions showed rapid progression to entirely enhanced lesions, i.e. overt HCC. Dynamic CT is recommended as one of the low-invasive imaging modalities to follow the hypoattenuating nodules and to determine the optimal treatment with careful attention being given to intratumoral attenuation conversion.

Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan, Department of Diagnostic Radiology, Seoul National University Hospital, The Korean Liver Cancer Study Group, Seoul, South Korea, Division of Gastroenterology and Hepatology, Taipei City Hospital, Taipei, Taiwan, Department of Surgery, Graduate School of Medicine, Kyoto University, The Liver Cancer Study Group of Japan, Kyoto, Japan, Social Insurance Alliance Shimonoseki Kohsei Hospital, Yamaguchi, Japan, Department of Internal Medicine and Radiology, Taipei City Hospital, Taipei, Taiwan, Department of Hepato-Gastroenterology, Yuan’s General Hospital, Kaohsiung, Taiwan and The Liver Cancer Study Group of Taiwan

Purpose: To elucidate the morphologic appearance of small non-tumorous arterioportal (AP) shunts mimicking hepatocellular carcinoma on helical computed tomography (CT), their associated outcomes, and their relationship with alpha-fetoprotein levels in patients with chronic liver disease. Materials and Methods: Ten patients with multiple AP shunts on dynamic helical CT were evaluated. A non-tumorous AP shunt was defined as no increase or spontaneous regression in size on follow-up CT scans. The number and shape of shunts more than 5 mm in diameter were studied on a segment-by-segment basis on the initial CT scan, and compared with those on follow-up CT scans. Alpha-fetoprotein levels were measured at the same time as CT scanning was performed. Results: Ten patients with 86 AP shunts (range 0.5–3.8 cm; mean 1.2 cm) underwent arterial, portal and delayed phase imaging of the entire liver. The AP shunts were geographic (44%), round (33%) or wedge-like (23%) in shape. All shunts changed from high- to iso-attenuation on the delayed phase CT. A follow-up CT (mean 73 days) revealed spontaneous disappearance in all but three (97%) of the 86 AP shunts. Furthermore, 16 new shunts appeared in different segments from the primary ones in four patients. The rapid elevation of alpha-fetoprotein levels to 5–10-fold higher than the baseline level was recognized at the same time as the initial appearance of AP shunts in three patients (30%). Further follow-up CT scans detected solitary hepatocellular carcinomas in four patients at a mean 1283 days after the initial CT. The location of the hepatocellular carcinomas was quite different from those of the initially recognized AP shunts. Conclusions: Non-tumorous AP shunts varied in CT appearance and demonstrated iso-attenuation in the delayed phase, most of which disappeared within 4 months. For these multiple small stains in chronic liver disease, periodic follow-up CT is recommended rather than alternative invasive interventions, even though there was an association with rapid elevation of alpha-fetoprotein levels.

Gastrointestinal hemorrhage from hepatocellular carcinoma invading the duodenum is very rare. A 60-year-old man with multiple hepatocellular carcinoma was admitted to our hospital because of massive melena and hematemesis. We succeeded in hemostasis of an esophageal variceal rupture by endoscopic varicial ligation. The duodenum could not be observed endoscopically due to extramural compression to the stomach from the liver tumor. Massive gastrointestinal hemorrhage occurred again and the patient died of hepatic failure. The postmortem examination revealed that the liver tumor had invaded the second portion of the duodenum and perforated into the lumen.

We report a 41-year-old woman with a retroperitoneal schwannoma mimicking hepatic tumor in the caudate lobe. Dynamic computed tomography in the early phase showed an enhanced tumor (2.7 cm in diameter) in the Spiegel lobe of the liver, which compressed the inferior vena cava (IVC). We also performed left hepatic angiographic computed tomography, and found that the tumor was less enhanced. The patient underwent laparotomy under a preoperative diagnosis of primary hepatic caudate tumor with faint neovascularity. At surgery, the tumor was found to be located between the left caudate lobe and the IVC, and was resected as being of a retroperitoneal origin. This case illustrates that tumor location must be determined with great care when the mass seems to exist at the dorsal edge of the liver, and especially when the tumor is hypovascular.

For patients with hepatocellular carcinoma (HCC), the selection of effective therapeutic options depends on a reliable prognostic assessment of both the tumor characteristics and liver impairment. This study sought to provide a modified Japan Integrated Stage (m-JIS) score to predict more accurately the survival of patients with HCC.We analyzed the records of 42,269 patients diagnosed with HCC that were registered between 1992 and 1999 in a nationwide Japanese database. The m-JIS score was calculated from the tumor-node-metastasis stage and the grade of liver damage as defined by the Liver Cancer Study Group of Japan. The predictive accuracy for patient survival based on the m-JIS score was compared with that determined by the modified Cancer of the Liver Italian Program (m-CLIP) score using the cross-validation method.Patients were divided randomly into two groups, a training sample for construction of prediction models (n = 21,127 patients with 8,458 deaths) and a validation sample for assessment of those prediction models (n = 21,142 patients with 8,434 deaths). Both the m-JIS score and the m-CLIP score showed good discriminatory ability in the training sample. In the validation sample, the residuals of prediction based on the m-JIS score were smaller than those of the m-CLIP score (P0.0001).The m-JIS scoring system had better predictive accuracy than the m-CLIP score system for survival of Japanese patients with HCC.