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A 77-year-old man presented to our hospital with diarrhea and weight loss. Upper gastrointestinal endoscopy revealed advanced Type 3 gastric cancer measuring 40 mm in the lower greater curvature of the stomach. Biopsy from a gastric tumor revealed moderately differentiated tubular adenocarcinoma overexpressing HER2. Abdominal contrast-enhanced computed tomography(CT)showed multiple liver metastases in S3 and S5. We diagnosed HER2-positive gastric cancer with liver metastasis. Systemic chemotherapy was administrated, with a total of 13 courses of combination therapy with S-1, oxaliplatin and trastuzumab. After chemotherapy, the primary tumor was significantly reduced and liver metastases were almost undetectable. Laparoscopic distal gastrectomy and partial hepatectomy were performed as conversion surgery. The patient was discharged on the 9th day without any postoperative complications. Postoperative pathological findings showed no residual tumor in either gastric and hepatic specimens, and the therapeutic effect of chemotherapy was diagnosed as pathological complete response. We report a case of HER2-positive advanced gastric cancer with multiple liver metastases that achieved a pathologically complete response to chemotherapy followed by conversion surgery. Laparoscopic surgery would be one of an effective option for conversion surgery.

The pathological conditions of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) are the major risk factors for hepatocellular carcinoma (HCC). Exposure to DNA-damaging agents such as ionizing radiation is another risk factor for HCC; calorie restriction (CR), however, effectively delays the onset of radiation-induced HCC. We investigated whether NASH is relevant to radiation-induced HCC and the cancer-preventing effect of CR. Eight-day-old male B6C3F1 mice were irradiated with 3.8 Gy of X-rays and then fed a standard diet or 30% CR diet from 49 days of age until necropsy, which was performed from 56 to 600 days with ~100-day intervals to assess both pathological changes and gene expression levels. We found that early-life exposure to radiation accelerated lipid accumulation and NASH-like histopathological changes in the liver, accompanied by accelerated development of HCC. CR ameliorated the changes in lipid metabolism in the liver and reversed the NASH-like pathology, which effectively delayed HCC development. Gene-expression profiling revealed the radiation-related activation and CR-related suppression of the peroxisome proliferator-activated receptor gamma/Cd36 pathway of transmembrane fatty-acid translocation before development of the NASH-like state. Thus, early-life exposure to radiation affects lipid metabolism and induces a steatoinflammatory microenvironment that favors HCC development. Therefore, targeting this pathway by CR (or measures that mimic CR) may be a promising strategy for preventing HCC caused by either radiation or other DNA-damaging agents., (© 2023 UICC.)

In malignant pheochromocytoma, the survival benefit of metastasectomy remains unclear. However, excessive catecholamines secreted from pheochromocytomas can cause cardiovascular and cerebrovascular complications. Debulking metastasectomy can be performed to reduce excess catecholamine secretion when curative resection is impossible. We present a case of metastatic pheochromocytoma to the liver, wherein a significant reduction in catecholamine secretion was achieved by repeat debulking hepatectomy. A 62-year-old woman who had undergone left adrenalectomy for primary pheochromocytoma 10 years prior to our surgical management, had multiple liver metastases of pheochromocytoma. Curative hepatectomy was infeasible because of insufficient remnant liver volume; thus, debulking hepatectomy was conducted. Preoperatively, increased doses of alpha-blockers and catecholamine synthesis inhibitors were administered. Nevertheless, substantial fluctuations in blood pressure and massive hemorrhage were observed intraoperatively. Eight months after the initial hepatectomy, repeat hepatectomy for the remnant lesions was performed due to the worsening of catecholamine levels and catecholamine-related symptoms. The patient survived, with serum catecholamines remaining within the normal range after repeat hepatectomy. Repeat debulking hepatectomy for metastatic pheochromocytoma to the liver is a feasible treatment strategy to effectively decrease catecholamine secretion and alleviate the symptoms thereof. However, special attention should be paid to perioperative catecholamine management and intraoperative surgical techniques., (© 2023. Japanese Society of Gastroenterology.)

We experienced a case of breast cancer in which liver metastases spread rapidly and the patient died of pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a fatal cancer-associated respiratory complication disease. To reveal genetic alterations of the clinical course, we performed next generation sequencing of the serial specimens using the Ion AmpliSeqTM Comprehensive Cancer Panel and RNA sequencing for transcriptomic data, followed by gene set analysis. The analysis revealed an oncogenic TP53 R213* mutation in all specimens and STK11 loss in tissues sampled after disease progression. Immunohistochemistry with an anti-STK11 antibody confirmed no STK11 expression in the samples after progression. Transcriptome analysis showed a significant downregulation of proteins associated with apoptosis in the specimens with STK11 loss. STK11 loss may have triggered the rapid progression of PTTM from a comprehensive genomic analysis.

Background/aim: We aimed to evaluate the correlation between stroke volume variation (SVV) and intraoperative blood loss (IBL) in hepatocellular carcinoma (HCC) resection and examine the perioperative utility of SVV-based management., Patients and Methods: Ninety-five patients who underwent partial or sub-segmental hepatectomy for HCC between 2013 and 2019 at the University of Yamanashi Hospital were retrospectively analyzed. A correlation analysis between IBL and SVV was performed, and then all cases were divided into three groups: high, middle, and low-SVV groups. Perioperative short-term outcomes based on SVV groups were analyzed., Results: There was a weak but significant negative correlation between SVV and IBL (ρ=-0.372, p<0.001). Comparative analysis revealed that low-SVV was associated with a high incidence of postoperative complications and blood transfusion (p=0.018 and 0.037, respectively), and high-SVV was not related with postoperative complications., Conclusion: SVV-based management is a significant and feasible strategy to achieve safe and exact surgical resection of HCC., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Inhibition of metastasis through upregulation of immune surveillance is a major purpose of chemokine gene therapy. In this study, we focused on a membrane-bound chemokine CXCL16, which has shown a correlation with a good prognosis for colorectal cancer (CRC) patients., Methods: We generated a CXCL16-expressing metastatic CRC cell line and identified changes in TNF and apoptosis-related factors. To investigate the effect of CXCL16 on colorectal liver metastasis, we injected SL4-Cont and SL4-CXCL16 cells into intraportal vein in C57BL/6 mice and evaluated the metastasis. Moreover, we analyzed metastatic liver tissues using flow cytometry whether CXCL16 expression regulates the infiltration of M1 macrophages., Results: CXCL16 expression enhanced TNF-α-induced apoptosis through activation of PARP and the caspase-3-mediated apoptotic pathway and through inactivation of the NF-κB-mediated survival pathway. Several genes were changed by CXCL16 expression, but we focused on IRF8, which is a regulator of apoptosis and the metastatic phenotype. We confirmed CXCL16 expression in SL4-CXCL16 cells and the correlation between CXCL16 and IRF8. Silencing of IRF8 significantly decreased TNF-α-induced apoptosis. Liver metastasis of SL4-CXCL16 cells was also inhibited by TNF-α-induced apoptosis through the induction of M1 macrophages, which released TNF-α. Our findings suggest that the accumulation of M1 macrophages and the enhancement of apoptosis by CXCL16 might be an effective dual approach against CRC liver metastasis., Conclusions: Collectively, this study revealed that CXCL16 regulates immune surveillance and cell signaling. Therefore, we provide the first evidence of CXCL16 serving as an intracellular signaling molecule.

Purpose: To clarify the diagnostic performance of gadoxetic acid-enhanced MRI for the detection of hepatocellular carcinoma (HCC) in recipients of living related-liver transplantation (LRLT)., Materials and Methods: This retrospective study group consisted of 15 patients with 61 HCCs who each underwent multidetector row computed tomography (MDCT), gadoxetic acid-enhanced MRI, and angiography-assisted computed tomography (CT) before LRLT. The three modalities were compared for their ability to detect HCC. Two blinded readers independently reviewed the images obtained by each modality for the presence of HCC on a segment-by-segment basis using a 5-point confidence scale. The diagnostic performance of the modalities was evaluated in a receiver operating characteristic (ROC) analysis. The area under the ROC curve (Az), sensitivity, specificity, and accuracy were compared for the three modalities., Results: No significant difference in Az, sensitivity, specificity, or accuracy was obtained among gadoxetic acid-enhanced MRI, MDCT, and angiography-assisted CT for both readers. For reader 1, the sensitivity (55.6%) and the accuracy (84.7%) of angiography-assisted CT were significantly higher than those of MDCT (33.3% and 78.0%) (P < 0.05)., Conclusion: Gadoxetic acid-enhanced MRI has a relatively high diagnostic ability to detect HCC even in recipients of LRLT, equivalent to the abilities of MDCT and angiography-assisted CT., (© 2013 Wiley Periodicals, Inc.)

Background and Aim: A faint hypointensity in the noncancerous tissue around hepatocellular carcinoma (HCC) in the hepatobiliary phase of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) is encountered. The goal is to elucidate the significance of this type of pseudolesion designated as the peritumoral decreased uptake area of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) (PDUAE)., Methods: This study group consisted of 61 patients with 61 surgically resected HCCs who underwent preoperative Gd-EOB-DTPA-enhanced MRI. The presence of a faint and hypointense area around the tumor in the hepatobiliary phase was defined as PDUAE. The frequency with which PDUAE was seen was compared between pairs of groups determined by clinical and pathological parameters using a Fisher's exact probability test. The parameters showing significant differences in this test were further tested by multiple logistic regression analysis., Results: PDUAE was observed in 25 cases. In univariate analysis, the values of alpha-fetoprotein and protein-induced by vitamin K absence or antagonist-II, maximal diameter, the presence of a capsule, and vascular invasion were significantly correlated with the frequency with which PDUAE was seen. In multivariate analysis, only maximal diameter and vascular invasion were significantly correlated. When the presence of PDUAE was used as an indicator of vascular invasion, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 72%, 80.6%, 77%, 72%, and 80.6%, respectively., Conclusions: By using this indicator, "microscopic" vascular invasion of HCC can be easily predicted with Gd-EOB-DTPA-enhanced MRI., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

The purpose of this study was to determine the utility of triple-phase helical computed tomography (CT) for differentiating canine hepatic masses. Seventy dogs with hepatic masses underwent triple-phase CT followed by surgical removal of the hepatic masses. Triple-phase helical CT scans for each dog included precontrast, arterial phase, portal venous phase, and delayed phase studies. The removed hepatic masses were histopathologically classified as hepatocellular carcinoma (n = 47), nodular hyperplasia (n = 14), and hepatic metastatic tumors (n = 9) in dogs. Of the 47 hepatocellular carcinomas, the most common CT findings included a heterogeneous pattern with hyper-, iso-, and hypoenhancement in both the arterial and portal venous phases (40/47, 85.1%). Of the 14 nodular hyperplasias, the most common CT findings were a homogeneous pattern with hyper- and isoenhancement in both the portal venous and delayed phases (13/14, 92.9%). Of nine hepatic metastatic tumors, the most common CT findings included a homogeneous hypoenhancement pattern in both the arterial and portal venous phases (8/9, 88.9%). In addition, 5 (55.6%) showed homogeneous hypoenhancement patterns in the delayed phase. Findings from our study indicated that triple-phase CT is a useful tool for preoperative differentiation of hepatocellular carcinoma, nodular hyperplasia, and hepatic metastatic tumors in dogs., (© 2013 American College of Veterinary Radiology.)

Objective: An outbreak of bile duct carcinoma has been reported among workers in a certain printing company in Osaka, Japan, where there was no descriptive epidemiological study. We conducted descriptive studies of bile duct carcinoma in Osaka., Methods: Based on the data from the Osaka Cancer Registry, the incidence and survival rate of intrahepatic and extrahepatic bile duct carcinomas, gallbladder carcinomas and hepatocellular carcinomas were analyzed. The study period was between 1975 and 2007, and total 108 407 incidents were retrieved from the Osaka Cancer Registry. Age- and sex-specific incidence rates and age-standardized incidence rates were calculated. Standardized incidence ratios were evaluated for each municipality in Osaka prefecture. Relative 5-year survival rates were also calculated for the cases diagnosed between 1993 and 2005., Results: Age-standardized incidence rates of bile duct carcinomas increased distinctly from the middle of the 1970s to the early 1980s in males and the 1990s in females. However, no distinct increase in the incidence rates was observed in 2000. Standardized incidence ratios of those did not exceed the unity significantly in males between 1992 and 2007. In females, standardized incidence ratios exceeded the unity significantly in a few regions without any relation to the location of the printing company where the outbreak was reported. The relative 5-year survival rate is generally poor; however, patients who were diagnosed with localized disease at the age of 25-49 years showed a better survival., Conclusion: Neither change in trend nor regional accumulation of bile duct carcinoma was confirmed in Osaka, corresponding to the outbreak reported in the printing company.

Background: A trial was conducted to evaluate the feasibility, efficacy, and safety of biweekly administration of irinotecan, a novel topoisomerase I inhibitor, for patients with metastatic breast cancer (MBC) previously treated with either anthracycline-based or taxane-based chemotherapy., Methods: Eligible patients were HER2-negative, had a performance status of 0 to 2, and had been treated previously with either anthracyclines or taxanes for MBC. Patients received irinotecan intravenously at 150 mg/m(2) on days 1 and 15 every 4 weeks. The primary end-point was feasibility, and the treatment was considered feasible if a patient was able to receive three administrations of irinotecan within the first 8 weeks, as pre-specified in the protocol., Results: Eighteen patients (median age 60 years) were enrolled. Fifteen patients received irinotecan more than 3 times within the first 8 weeks, with resulting feasibility of 83.3%. The median number of treatment cycles was 2 (range 1-16) during this period, and the relative dose intensity was 91.2%. Partial response was observed for one patient, so overall response rate was 5.6%. Nine patients (50.0%) had stable disease, and overall disease control was 50.0%. Median progression-free survival and overall survival periods were 3.2 and 9.6 months, respectively. The only grade 3/4 hematological toxicity was neutropenia (22.2%). Grade 3/4 non-hematological toxicities were anorexia (11.2%), diarrhea (11.2%), and fatigue (5.6%). No treatment-related death occurred., Conclusions: This study demonstrated that biweekly administration of 150 mg/m(2) irinotecan was feasible for patients with MBC treated previously with anthracyclines or taxanes.

Colorectal cancer (CRC) is a typical lifestyle-related disease, and it metastasizes mostly to the liver. It is important to understand the molecular mechanisms of CRC metastasis in order to design new and effective treatments for CRC patients. Chemokines are known to have antitumor effects as their chemoattractant properties stimulate the accumulation of infiltrating immune cells (TILs) in tumors. Chemokine (C-X-C motif) ligand 16 (CXCL16), also known as SR-PSOX, is a unique membrane-bound chemokine that induces the expression of its specific receptor CXCR6. We previously reported that the expression of CXCL16 by cancer cells enhances the recruitment of TILs, thereby improving the prognosis of CRC. It has since been reported that CXCL16/CXCR6 expression is involved in the metastasis of various types of cancer. However, there is no report of the association between CXCL16 expression and liver metastasis in CRC. In this study, we investigated the role of cancer-derived CXCL16 and the possibility of gene therapy using CXCL16. Therefore, we examined the metastasis of colon 38 SL4 cells to the liver in an experimental model. Following injection of cancer cells into the intraportal vein, CXCL16-expressing CRC cells drastically inhibited liver metastasis. We also found that CD8 T cells and natural killer T (NKT) cells, known as CXCR6-expressing cells, increased in CXCL16-expressing metastatic tissue. Collectively, the inhibitory effect on metastasis to the liver by CXCL16 was observed in NKT cell-depleted mice but not in CD8 T cell-depleted mice. These results demonstrate the inhibitory effect of CXCL16 on liver metastasis via NKT cells in CRC.

Purpose: To elucidate whether the attenuation of hypervascular hepatocellular carcinoma (HCC) on the portal phase of dynamic CT is correlated with histological grade., Materials and Methods: This study group consisted of 66 patients with 74 surgically resected, hypervascular HCCs. On a preoperative dynamic study with a 64-multidetector row CT, the portal phase was scanned 60 s after injecting the contrast agent following the pre-contrast image and hepatic arterial phase. The tumor attenuation of each HCC on the portal phase was categorized into high, iso-, or low, and was compared with the predominant histological grade using Mann-Whitney's U test., Results: Twenty-nine, 29, and 16 HCCs showed high, iso-, and low attenuation on the portal phase, respectively. Tumors were classified into three well- (w-), 58 moderately (m-), or 13 poorly (p-) differentiated HCCs. The tumor attenuation of p-HCC on the portal phase was significantly lower than those of w-HCC and m-HCC (p < 0.05 and p < 0.00001)., Conclusion: The tumor attenuation on the portal phase may help when diagnosing the histological grade of hypervascular HCC. p-HCC are considered to show a faster contrast washout than w-HCC and m-HCC.

Purpose: To evaluate the efficacy of the dual-source parallel radiofrequency system (DS system) for gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI)., Materials and Methods: Twenty-six subjects with liver diseases underwent hepatobiliary phase imaging of Gd-EOB-MRI using either the DS system or a single-source radiofrequency system with or without body-tuned CLEAR, which is a post-processing correction method of B1 inhomogeneity-induced signal loss (SSBTC+ and SSBTC-, respectively). The left and right lobes of the liver were separately assessed. Qualitatively, the homogeneity of signal intensity distribution was scored using a 3-point scale. Quantitatively, lesion-to-liver and spleen-to-liver contrast ratios (CRs) were calculated. The scores and CRs were compared among the three techniques by two-way analysis of variance and Tukey's Honestly Significant Difference post hoc test. Values of p<0.05 were considered statistically significant for each analysis., Results: The DS system showed a significantly better score in the left lobe of the liver, and higher lesion-to-liver and spleen-to-liver CRs in the left and right lobes of the liver, compared with SSBTC+ or SSBTC- (p<0.05). The DS system and SSBTC- showed no significant differences in scores in the right lobe of the liver but they showed significantly better scores than SSBTC+ (p<0.05)., Conclusion: The DS system is more advantageous to improve the homogeneity of signal intensity distribution and tissue contrast of Gd-EOB-MRI than the post-processing correction method independently of the site., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate the predictive factors of malignant transformation of hypovascular hepatic nodule showing hypointensity in the hepatobiliary phase images of gadoxetic acid-enhanced MRI (HHN)., Materials and Methods: The clinical data and imaging findings of dynamic contrast-enhanced computed tomography (DCE-CT) and gadoxetic acid-enhanced MRI for a total of 103 HHNs in 24 patients with chronic liver disease were retrospectively investigated. After the results of follow-up examinations were investigated, HHNs were categorized into the three groups for each comparison: (1) nodules with enlargement and/or vascularization and others, (2) nodules with only enlargement and others, (3) nodules with only vascularization and others. Enlargement and/or vascularization during the follow-up period were defined as malignant transformation of HHN. The frequency of each clinical datum and imaging finding in each group was compared to identify the predictive factors for malignant transformation in HHN., Results: Multivariate analysis showed that a nodule size of 9 mm or more on the initial gadoxetic acid-enhanced MRI was a significant predictive factor for the enlargement and/or vascularization of HHN (P<0.05). On the other hand, the hypoattenuation on the delayed phase imaging of the initial DCE-CT was a significant predictive factor for the enlargement or vascularization of HHN (P<0.05)., Conclusion: A nodule size of 9 mm or more on the initial gadoxetic acid-enhanced MRI and hypoattenuation on the delayed phase imaging of initial DCE-CT would be helpful for predicting the outcome of HHN in patients with a risk of hepatocellular carcinoma., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To elucidate the correlation between hypervascular hepatocellular carcinoma (HCC) enhancement patterns on dynamic MR imaging and histological findings., Materials and Methods: Surgically proven 46 hypervascular HCCs of forty-one patients were enrolled. For each HCC, the signal intensity in the portal phase (SIPP) was evaluated. In this study, high, iso-, or low intensity in the portal phase was hypothesized as late, moderate, or early washout pattern, respectively. The SIPP of each HCC was correlated to histological grade and architectural subtypes that represent degrees of trabecular structure. For the trabecular HCCs, the thickness of tumor plate was also correlated for indirect estimation of tumor sinusoid., Results: There was a significant correlation between the SIPP vs. histological grade and also vs. architectural subtypes, namely the degree of trabecular structure. Washout of hypervascular HCC occurred earlier as the histological grade advanced and the histological architecture got closer to pure trabecular HCC. For the trabecular HCCs, the thickness of tumor plate correlated significantly with SIPP or histological grade. Hypervascular HCCs with thicker tumor plates showed worse histological grade and earlier washout pattern., Conclusions: Histological grade of hypervascular HCC may be predicted using SIPP. The thickness of tumor plate, resultantly the size of sinusoid between tumor plates, can account for the relationship between washout pattern and histological grade in the trabecular HCCs., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To examine whether or not the parameters regarding the signal intensity of the liver parenchyma on superparamagnetic iron oxide (SPIO)- and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI are correlated with the parameters of Technetium-99m galactosyl serum albumin ((99m)Tc-GSA) scintigraphy., Materials and Methods: This retrospective study consisted of 55 and 33 patients who underwent SPIO- and Gd-EOB-DTPA-enhanced MRI in addition to (99m)Tc-GSA scintigraphy, respectively. For each patient, we calculated Pre R2* and Pre R2, which are equivalent to R2* (=1/T2*) and R2 (=1/T2) values of the liver parenchyma; ΔR2* and ΔR2, which represent differences in R2* and R2 values of the liver parenchyma before and after administration of SPIO; and the increase rates of both the liver-to-spleen signal intensity ratio (LSR) and the liver-to-major psoas muscle signal intensity ratio (LMR) on the hepatobiliary phase compared with the precontrast image. For (99m)Tc-GSA scintigraphy, the receptor index LHL15 and the blood clearance index HH15 were recorded., Results: Regression analysis showed a moderate correlation between Pre R2* and LHL15 (P<0.05). Mild to moderate correlations were also obtained between any combination of ΔR2* and ΔR2 on the one hand, and LHL15 and HH15 on the other (P<0.05). There were moderate correlations between any combination of increase rates of LSR and LMR on the one hand, and LHL15 and HH15 on the other (P<0.05-0.001)., Conclusion: Pre R2*, ΔR2*, ΔR2 and the increase rates of LSR and LMR could be used as quantitative indicators of liver function., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background/aims: Little information is available about the long-term prognosis after hepatectomy for liver metastases of neuroendocrine tumors (NETs). To clarify the prognosis for liver metastases of NETs after hepatectomy and to identify a practical and useful surgical indication for hepatic metastases of NETs., Methodology: Twenty-four patients with NET were divided into 2 groups: the nHM group (patients without hepatic metastasis, n=13) and the HM group (patients with hepatic metastasis or recurrences, n=11). Hepatectomy was indicated for metastases or disease recurrences in the liver if R0 resection was expected to be achievable. Patient clinicopathological features, mode of recurrences and treatment for them were evaluated retrospectively., Results: The median follow-up period for the 24 patients was 34 months (range 7-69) and the disease specific survival rate was 82% at 5 years. DSS at 5 years did not differ between patients with and without hepatic recurrence (91% vs. 75% respectively, p=0.6144), even though the histological grade and the MIB-1 index were higher in the HM group., Conclusions: Patient prognosis was acceptable following our policy of hepatectomy for NET liver metastases. Survival could be improved by intensive multimodal treatment.

Background: A high incidence of recurrence after treatment is the most serious problem in hepatocellular carcinoma (HCC). Therefore, a new strategy for the treatment of the disease is needed. The aim of the present study was to investigate whether vitamin D binding protein-macrophage activating factor (DBP-maf) is able to inhibit the growth of HCC., Methods: The effects of DBP-maf on endothelial cells and macrophage were evaluated by WST-1 assay and phagocytosis assay, respectively. Human HCC cells (HepG2) were implanted into the dorsum of severe combined immunodeficiency (SCID) mice. These mice were divided into control and DBP-maf treatment groups (n = 10/group). The mice in the treatment group received 40 ng/kg/d of DBP-maf for 21 d., Results: DBP-maf showed anti-proliferative activity against endothelial cells and also activated phagocytosis by macrophages. DBP-maf inhibited the growth of HCC cells (treatment group: 126 ± 18mm(3), untreated group: 1691.5 ± 546.9mm(3), P = 0.0077). Histologic examinations of the tumors revealed the microvessel density was reduced and more macrophage infiltration was demonstrated in the tumor of mice in the treatment group., Conclusion: DBP-maf has at least two novel functions, namely, an anti-angiogenic activity and tumor killing activity through the activation of macrophages. DBP-maf may therefore represent a new strategy for the treatment of HCC., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the characteristics of hepatocellular carcinomas (HCCs) with marginal superparamagnetic iron oxide (SPIO) uptake on T2*-weighted MRI., Materials and Methods: The study group consisted of 73 patients with 83 surgically resected HCCs. Preoperative SPIO-enhanced MRI studies were retrospectively reviewed. Marginal SPIO uptake was considered positive if a rim-like or band-like low intensity area was present on SPIO-enhanced T2*-weighted images. The prevalence of marginal SPIO uptake was evaluated. Pathological specimens with hematoxylin and eosin staining and immunohistochemical staining of CD68 were reviewed in HCCs with marginal SPIO uptake and 33 HCCs without marginal SPIO uptake (control group)., Results: Ten of 83 (12%) HCCs showed marginal SPIO uptake. All HCCs were hypervascular, and only one nodule showed a nodule-in-nodule appearance on imaging findings. The pathology specimens suggested possible causes of marginal SPIO uptake, including marginal macrophage infiltration in moderately or poorly differentiated HCC (n=4), residual normal hepatic tissue at the marginal area of confluent multinodular or single nodular with extranodular growth type HCC (n=3), and a well-differentiated HCC component in nodule-in-nodule type HCC (n=3). Marginal macrophage infiltration was not seen in the control group., Conclusion: SPIO-enhanced MRI may be able to demonstrate marginal macrophage infiltration in HCC., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The aim of this study was to reveal the relationship between intratumoral uptake of gadoliniumethoxylbenzyldiethylenetriaminepentaacetic acid (Gd-EOB-DTPA) of hepatocellular carcinoma (HCC) in the hepatobiliary phase and pathological features., Materials and Methods: Sixty HCC nodules were confirmed at pathology in 56 patients who had undergone dynamic MRI. T1-weighted 3D gradient echo sequences before and 20 min (hepatobiliary phase) after the injection of Gd-EOB-DTPA were performed. Uptake of Gd-EOB-DTPA was defined as an increase in signal intensity in the hepatobiliary phase compared with the precontrast scan. All surgical specimens were fixed with formalin and then digitally photographed. The relationship between Gd-EOB-DTPA uptake and histological findings, including a macroscopic greenish area, was examined., Results: MR images showed uptake of Gd-EOB-DTPA in twenty-two nodules. Histological findings indicated twenty-six nodules contained a greenish area. There is a significant correlation between HCC showing Gd-EOB-DTPA uptake and the presence of a greenish area (p<0.001). On a nodule-by-nodule basis, more than two-thirds of the area of Gd-EOB DTPA uptake coincides with the greenish part in only 12 of 22 lesions (54.5%). More than two-thirds of the greenish area coincided with that of Gd-EOB-DTPA uptake in only 10 of 26 cases (38.5%)., Conclusion: The area of Gd-EOB-DTPA uptake does not always match the greenish part, but HCC with uptake of Gd-EOB-DTPA significantly correlated with green HCC., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate whether the histological grade of hepatocellular carcinoma (HCC) can be predicted using the apparent diffusion coefficient (ADC)., Materials and Methods: This retrospective study group consisted of 80 patients with 85 surgically resected HCCs who underwent preoperative MRI exams including diffusion-weighted imaging. The tumors were histologically classified into five groups as follows: five well (w-), 17 well to moderately (wm-), 37 moderately (m-), 16 moderately to poorly (mp-), and 10 poorly (p-) differentiated HCCs. For ADC measurement of each HCC, the largest possible region of interest was placed on the solid region on the ADC map where ADC was considered to be the lowest. The average ADCs of the five histological grades were compared using Spearman's rank correlation test and Student's t-test, and the diagnostic performance of ADC for mp- and p-HCCs was also evaluated using a receiver operating characteristic-based positive test., Results: The average ADC of p-HCC (0.76±0.10×10(-3) mm2/s) was significantly lower than those of the other four histological grades. The average ADC of mp-HCCs (0.99±0.20×10(-3) mm2/s) was significantly lower than those of w-, wm- and m-HCCs. The sensitivity, specificity, PPV, NPV, and accuracy, when an ADC of 0.972 or lower was considered an indicator of mp- and p-HCCs, were 73.1%, 72.9%, 54.3%, 86.0% and 72.9%, respectively., Conclusion: ADCs of mp- and p-HCCs were lower than those of w-, wm- and m-HCCs. ADC can contribute to radiological diagnosis of poorly differentiated components in HCCs., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Microvessel count (MVC) has been correlated with patient prognosis in hepatocellular carcinoma. We investigated whether MVC assessed by staining with CD34 antibody was associated with disease-free and overall survival in patients with metastatic liver cancer (MLC)., Methods: We examined relationships between MVC and clinicopathologic factors or postoperative outcomes in 139 MLC patients who underwent hepatectomy between 1990 and 2006. CD34 expression was analyzed by the immunohistochemical method., Results: MVC was associated with fibrous pseudocapsular formation on histological examination. By means of the modern Japanese classification of liver metastasis, poorer survival was associated with higher score, poorly differentiated adenocarcinoma, higher preoperative carcinoembryonic antigen (CEA) level, fibrous pseudocapsular formation, and smaller surgical margin. Shorter disease-free survival was associated with higher score when the Japanese classification of liver metastasis was used, multiple or bilobar tumor, regional lymph node metastasis in primary colon carcinoma, preoperative CEA level, fibrous pseudocapsular formation, and smaller surgical margin (<5 mm). Higher MVC (>or=406/mm(2)) was associated with decreased disease-free and overall survival by univariate analysis (P = .034 and P = .021, respectively), and higher MVC represented an independently poor prognostic factor in overall survival by Cox multivariate analysis (risk ratio, 2.71; P = .023) in addition to histological differentiation., Conclusions: Tumor MVC seems to be a useful prognostic marker of MLC patient survival.

Background/purpose: The purpose of this work was to evaluate the short-term results of laparoscopic-assisted limited liver resection., Methods: We analyzed the clinical outcome in 17 patients (mean age 70 +/- 8 years) who had undergone laparoscopic-assisted limited liver resection from March 2006 to December 2008. Preoperative diagnoses were HCC in 13 patients and metastasis of colon cancer in 4. The operation consisted of laparoscopic mobilization of the target liver lobe, followed by open liver resection through a 7- to 10-cm extraction site., Results: Mean tumor size was 3.0 +/- 1.1 cm (range 1.2-5 cm). The mean operative time was 362 +/- 85 min. The mean blood loss was 451 +/- 413 ml, and no blood transfusion was required in any patient. There were no intraoperative complications, and conversion to laparotomy was needed in one case. Postoperative complications developed in 4 cases (4 infections, 24%), all of which were improved by conservative management. However, there was no postoperative mortality. None of the patients had any peritoneal carcinomatosis or port-site or resection site recurrence during a mean follow-up of 18 +/- 9.6 months. According to the analysis of the tumor location, the criterion for an adequate tumor location in the right lobe for this operation was set with the tumor at a distance of more than 5 cm from the inferior vena cava and the root of the hepatic vein (5 cm rule)., Conclusion: Laparoscopic-assisted limited liver resection is feasible and well tolerated. Accumulation of more data may be needed for evaluation of long-term outcome.

Aim: To elucidate the relationship between the microvessel count (MVC) by CD34 analyzed by immunohistochemical method and prognosis in hepatocellular carcinoma (HCC) patients who underwent hepatectomy based on our preliminary study., Methods: We examined relationships between MVC and clinicopathological factors in 128 HCC patients. The modified Japan Integrated Staging score (mJIS) was applied to examine subsets of HCC patients., Results: Median MVC was 178/mm(2), which was used as a cut-off value. MVC was not significantly associated with any clinicopathologic factors or postoperative recurrent rate. Lower MVC was associated with poor disease-free and overall survivals by univariate analysis (P = 0.039 and P = 0.087, respectively) and lower MVC represented an independent poor prognostic factor in disease-free survival by Cox's multivariate analysis (risk ratio, 1.64; P = 0.024), in addition to tumor size, vascular invasion, macroscopic finding and hepatic dysfunction. Significant differences in disease-free and overall survivals by MVC were observed in HCC patients with mJIS 2 (P = 0.046 and P = 0.0014, respectively), but not in those with other scores., Conclusion: Tumor MVC appears to offer a useful prognostic marker of HCC patient survival, particularly in HCC patients with mJIS 2.

Objective: The objective of this study was to evaluate whether minute portal venous invasion in hepatocellular carcinoma (HCC) can be diagnosed radiologically., Materials and Methods: CT hepatic arteriography and CT with arterioportography (CTAP) of 15 patients with minute portal venous invasion (group 1) and 30 patients without it (group 0) were evaluated. An area showing low attenuation on CTAP and high attenuation on CT hepatic arteriography around the tumor was defined as an area of peritumoral hemodynamic change. The shape and size of the area were compared between the two groups. The ratio of the area of peritumoral hemodynamic change volume to tumor volume (area volume-tumor volume ratio) was used as an indicator of the size of the area of peritumoral hemodynamic change and was categorized as one of three grades: grade I, 10% or less; grade II, between 10% and 30%; and grade III, 30% or more. The detectability of minute portal invasion was assessed when grade III was considered as an indicator. Each comparison was also made independently when the tumor diameter either was limited to less than 3 cm or was 3 cm or more., Results: Three types of area of peritumoral hemodynamic change were identified: wedge-shaped, belt-shaped or irregular, and linear. No significant difference in the frequency of each type of area of peritumoral hemodynamic change was observed between the two groups. The area volume-tumor volume ratio in group 1 was larger than that in group 0, with statistical significance when the tumor diameter was less than 3 cm (p = 0.046). Positive and negative predictive values were 71.4% and 75.0%, respectively, when the tumor diameter was less than 3 cm., Conclusion: The area of peritumoral hemodynamic change in HCC patients with minute portal invasion (group 1) may be larger than in those without it (group 0), especially when tumors are small.

We report a successful case of chemotherapy for primary far-advanced gastric cancer accompanied with poor general condition related to jaundice due to hepatic metastasis. A 54-year-old man, who had been admitted to another hospital in October 2006 with a complaint of tarry stool, was referred to our hospital. The result of detailed examination revealed an advanced gastric cancer, multiple lymph node metastases and jaundice (T-Bil 3.3 mg/dL) due to multiple hepatic metastases. The performance status (PS) was level 4. In parallel with a whole body control, a combined therapy with S-1 and CPT-11 was performed from October 27 as the first-line therapy. As a consequence of the first course, the jaundice disappeared. After the second course, the patient left the hospital. However, the patient was re-admitted to hospital in January 2007 by a reason of fever and a deterioration of PS. As exacerbation of cancerous peritonitis and the primary tumor were seen, a weekly paclitaxel therapy was performed as the second-line therapy. Two courses of treatment resulted in the disappearance of ascites and a reduction of hepatic/lymph node metastasis. PS was improved to level 0 as well. After these therapies, the patient was discharged from the hospital. As of June 2007, he continuously receives chemotherapy as an outpatient.

The patient was a 68-year-old woman who underwent left partial mastectomy on February 1999. The stage was T2N1. There were positive for estrogen and progesterone receptors in the tumor. After operation, adjuvant therapy consisting of oral administration of tamoxifen and radiation was performed. On February 2005, she felt dyspnea and right femoral pain. After examinations, she was diagnosed as recurrent breast cancer with pleuritis carcinomatosa and bone metastasis. The patient was treated with oral administration of anastrozole and pamidronate disodium 90 mg intravenously every 4 weeks, radiation of her right femur, and OK-432 injection into the intrapleural cavity. On November 2005, she felt general fatigue and anorexia. CT examination revealed multiple liver metastases. She was treated with oral combination chemoendocrine therapy with capecitabine (2,400 mg/day) and MPA (600 mg/day). After the four courses, multiple liver metastases were remarkably reduced in the CT findings. After twelve courses, the partial response continued. No adverse reactions occurred except for gain in weight of grade 1. It is suggested that this oral combination chemoendocrine therapy may be useful for recurrent breast cancer with consideration for treatment effectiveness and the quality of life of the patient.

Rationale and Objective: Our purpose in this study is to apply an artificial neural network (ANN) for differential diagnosis of certain hepatic masses on computed tomographic (CT) images and evaluate the effect of ANN output on radiologist diagnostic performance., Materials and Methods: We collected 120 cases of hepatic disease. We used a single three-layer feed-forward ANN with a back-propagation algorithm. The ANN is designed to differentiate four hepatic masses (hepatocellular carcinoma, intrahepatic peripheral cholangiocarcinoma, hemangioma, and metastasis) by using nine clinical parameters and 24 radiological findings in dual-phase contrast-enhanced CT images. Thus, the ANN consisted of 33 input units and four output units. Subjective ratings for the 24 radiological findings were provided independently by two attending radiologists. All clinical cases were used for training and testing of the ANN by implementation of a round-robin technique. In the observer test, CT images of all 120 cases (30 cases for each disease) were used. CT images were viewed by seven radiologists first without and then with ANN output. Radiologist performance was evaluated by using receiver operating characteristic (ROC) analysis on a continuous rating scale., Results: Averaged area under the ROC curve for ANN alone was 0.961. The diagnostic performance of seven radiologists increased from 0.888 to 0.934 (P < .02) when they used ANN output., Conclusion: The ANN can provide useful output as a second opinion to improve radiologist diagnostic performance in the differential diagnosis of hepatic masses seen on contrast-enhanced CT.

We report herein a case of hepatocellular carcinoma (HCC) with a prominent central scar. Dynamic CT and MRI studies revealed a hypervascular liver mass and a washout of contrast material in the delayed phase. The tumor center showed particular hyperintensity on T2-weighted images and delayed or prolonged enhancement. The surgical specimen revealed moderately differentiated HCC with a central scar. The central scar consisted of prominent vascular channels and loose fibrous tissue, indicative of a vascular scar. We should understand MR imaging findings of this type of central scar in the HCC.

A 54-year-old woman who had ascending colon cancer with multiple liver and lung metastases underwent rt. hemicolectomy and catheter insertion into the gastroduodenal artery for arterial infusion chemotherapy. On postoperative day 7, she had nausea and vomiting due to the enlarged multiple liver metastases on lateral segment. Intraarterial infusion of 5-FU 1,000 mg/m(2) for 5 hours weekly (WHF: weekly high-dose 5-FU) was started at first. After 3 courses, her symptoms improved, oral intake could be started, and liver metastases showed significant reduction on abdominal CT. Three months after surgery, bone scinti revealed multiple bone metastases. Combined HAI (5-FU: 600 mg/m(2)/3 hr) chemotherapy with UFT (400 mg/body) + CPT-11(80/body) and UFT (400 mg/body)/LV (75 mg/body) + CPT-11(100 mg/body) were effective for highly advanced colon cancer in terms of QOL. Eight months after surgery, she was doing well and the chemotherapy was continued. WHF therapy was effective for digestive symptoms due to liver metastasis.

A 87-year-old male underwent the extended hepatic left lobectomy and the partial hepatectomy (S7, S8) for liver hepatic metastasis from the rectal cancer in March 2003. The reserver was implanted by the GDA-coil method from the right femoral artery, and WHF was enforced 10 times. Epigastric and back pain appeared from January 2004. The pain became strong gradually. MRI and CT scan were examined after hospitalization. These imaging tests showed the pseudo aneurysm of common hepatic artery. Therefore, an emergency angiography was performed, and pseudo aneurysm of the common hepatic artery was embolized with 36 metallic coils. After the embolization, the pain had disappeared suddenly. The patient was discharged the 7th day after embolization. Hepatic arterial infusion chemotherapy is considered safe with respect to blood and non blood toxicity, which was compared with systemic chemotherapy. However, there were also complications like this case, and caution is required.

Objective: The purpose of this study was to evaluate the performance of enhanced CT in making a diagnosis of combined hepatocellular and cholangiocarcinomas (HCC-CCs) by comparing CT findings with histologic findings., Conclusion: One third (nine of 27 cases) of the combined HCC-CCs were correctly diagnosed on enhanced CT by detailed analysis of the enhancing pattern around or within the mass. Various factors such as an atypical enhancing pattern, the size of each component, and the presence of a mass composed of intermediate tumor cells-that is, cells with intermediate characteristics between HCC and CC-were found to be the causes of misdiagnosis of combined HCC-CC on enhanced CT.

We report 2 cases of synchronous bilobar multiple liver metastases from colorectal cancer which are hepatectomised following a hepatic arterial infusion chemotherapy. Both cases were considered unresectable metastases before chemotherapy. Case 1: A 55-year-old male, with rectal cancer and multiple hepatic metastases, was performed a low anterior resection. Hepatic arterial infusion chemotherapy (5-FU 1 g/m2 5h qw) and systemic chemotherapy (5-FU/LV) were administered. Twelve months after the first surgery, hepatectomy was performed. Case 2: Right hemicolectomy was performed on a 66-year-old male, with cancer of the transverse colon and multiple hepatic metastases. Hepatic arterial infusion chemotherapy was administered 38 times. Thirteen months after the first surgery, hepatectomy and MCT were performed. Even among the cases of unresectable hepatic metastases from colorectal cancer, there are some in which resection is possible followed by hepatic arterial infusion chemotherapy. Re-evaluation for hepatectomy is needed for the cases where hepatic arterial infusion chemotherapy is administered.

Objective: The purpose of this study was to clarify the usefulness of the test-injection method as compared with the fixed-time method in dynamic magnetic resonance (MR) imaging of hepatocellular carcinoma (HCC)., Methods: Ninety-seven patients with a total of 118 hepatocellular carcinomas underwent 3-dimensional fast imaging with steady-state free precession (3D-FISP) for dynamic study of the liver as well as catheter-assisted computed tomography hepatic angiography (CTHA) for preoperative evaluation. In 42 cases, the fixed-time method (30-second scan time delay in the hepatic arterial phase [HAP]) was performed (group 1), and in 55 cases, the test-injection method was performed (group 2). The following parameters were evaluated: 1) the adequacy of the HAP, 2) tumor vascularity using CTHA findings as a gold standard, and 3) the contrast-to-noise ratio (CNR) of the HCC during the HAP of dynamic MR imaging., Results: In group 1, 79% (33 of 42) of the cases were obtained at the optimal HAP; the percentage in group 2 was 98% (54 of 55) of the cases. This difference was statistically significant (P < 0.05). The vascularity of 82% of the tumors in group 1 and 89% of those in group 2 was diagnosed correctly. Regarding hypervascular tumors, correct evaluation of tumor vascularity was made in 87% of group 1 cases and 95% of group 2 cases. No significant difference was present between the 2 groups (total: P = 0.43, hypervascular HCC: P = 0.29). 3) The CNR calculated for all HCCs in group 2 (mean +/- SD: 8.66 +/- 11.0) was significantly higher than that for HCCs in group 1 (4.29 +/- 9.44; P < 0.05). As for the hypervascular tumors, the CNR calculated for group 2 (mean +/- SD: 9.89 +/- 10.6) was also significantly higher than that for group 1 (5.52 +/- 9.81; P < 0.05)., Conclusion: The 3D-FISP dynamic MR imaging using the test-injection method resulted in better demonstration of HCC than the 3D-FISP using the fixed-time method.

We present an 80-year-old-man who showed characteristic radiological findings of secondary hepatic malignant lymphoma. The patient was first admitted to our hospital 6 months before with left cervical mass, which was diagnosed as malignant lymphoma by biopsy. After complete response to chemotherapy, a large hepatic mass appeared, as the serum value of lactic dehydrogenase elevated. CT/MRI showed a well-demarcated hypovascular mass, which was penetrated by the right hepatic vein. The apparent diffusion coefficient of the mass was 0.70 x 10(-3) mm2/s. The patient was diagnosed as relapse of malignant lymphoma, mainly based on these radiological findings reflecting the mass with high cellularity which grows without destruction of existing vascular structure, and additional chemotherapy was given. The hepatic mass disappeared almost all and the serum value of lactic dehydrogenase decreased with in normal range. The patient was discharged in a good condition 2 months later.

A 65-year-old male underwent iliocecal excision and hepatic posterior segmentectomy for cecum cancer and synchronous liver hepatic metastasis in September and October 2001, respectively. A reservoir was implanted by the GDA-coil method from the right femoral artery in November, and WHF (5-FU 1,000 mg/m2) was administered 8 times. Because of the remnant liver recurrence, WHF was restarted in April 2002. Left leg paralysis appeared suddenly after the 3rd administration. Heparin and urokinase were administrated continuously after hospitalization. Also, liver function tests showed a worsening condition. The bile duct necrosis in the liver was examined with abdominal CT scan. The anti-coagulation therapy was changed to an oral drug on the 7th day after hospitalization. The liver function tests normalized gradually. Although the rehabilitation for leg paralysis performed during hospitalization was continued after discharge from the hospital, the patient is unable to walk and uses a wheelchair. Hepatic arterial infusion chemotherapy is considered safe for blood and non-blood toxicity compared with systemic chemotherapy. However, there are also complications as in this case, where QOL is reduced remarkably, and caution is required.

A case with liver metastasis from papillary renal cell carcinoma (RCC) is presented, in which intratumoral fat was detected on dual-echo chemical shift magnetic resonance imaging (MRI). The preoperative chemical shift MR image of the primary RCC also suggested the presence of intratumoral fat. Liver metastasis from fat-containing RCC should be included in the differential diagnosis of fat-containing liver masses as observed on chemical shift MRI.

Six patients with metastatic liver cancer (H3) and abnormal laboratory data for liver function underwent intra-hepatic arterial infusion (H.A.I.) therapy of high dose 5-FU (1 g/body/day, 6 days/week, 1q for 2 patients, 2q for 4 patients, with at least a one week interval). No serious side effects were observed in any case. Even in 2 cases with suspicious partial obstruction of the portal vein, no remarkable change in liver function was observed after high dose 5-FU H.A.I. therapy. Four patients who received 12 g of 5-FU showed a reduction in the abnormal data after a short transient rise in some cases. In 2 cases the reduction rate was high and the laboratory data were normalized in 3 months. A long PR was obtained in these cases. The other 2 cases, on the other hand, showed a low reduction rate and the liver function relapsed in a week. Tumor markers also returned to previous levels in a short period. These findings together imply that the reduction rate of abnormal liver function data might predict the efficacy of high dose 5-FU H.A.I. therapy.

Purpose: To determine the appropriate acquisition parameters for three-dimensional fast imaging with steady-state free precession (3D-FISP), to clarify the superiority of 3D-FISP to two-dimensional fast low-angle shot (2D-FLASH) on phantom study, and to clarify the clinical usefulness of 3D-FISP in diagnosing hepatocellular carcinoma (HCC)., Materials and Methods: 3D-FISP images with varying flip angles were compared by using a phantom. Signal-to-noise ratios (SNRs) and contrast-enhancement ratios (CERs) were compared for the four two-dimensional fast low-angle shot (2D-FLASH) sequences and 3D-FISP sequences in a phantom. The optimal 3D-FISP dynamic study was compared with plain, postcontrast MR sequences used to study 78 HCC cases and analyzed according to histological grade. The 3D-FISP image obtained 30 sec after gadopentetate dimeglumine (Gd) administration was also compared with CT hepatic angiography (CTHA)., Results: A 25 degrees flip angle and double-dose Gd administration were appropriate for 3D-FISP dynamic study. CER was the highest with 3D-FISP, and SNR was higher in 3D-FISP than in 2D-FLASH images in a phantom with high Gd concentration. Among the 105 lesions, 103 (98%) were depicted on 3D-FISP images. The detection rate of HCC on 3D-FISP was higher than 95% for each histological grade. The vascularity of the tumors as determined by CTHA findings was correctly diagnosed on 3D-FISP in 80% of cases., Conclusion: In phantom study, 3D-FISP with double-dose Gd injection showed higher contrast than 2D-FLASH as a sequence for liver dynamic study. In clinical study, 3D-FISP is useful in the detection of HCC, regardless of tumor vascularity and histological grade.

Background/aims: Ets-1 regulates the expression of a number of genes related to remodeling of the extracellular matrix. Ets-1 is associated with the occurrence of invasive processes, proliferation and differentiation. Less is known about the biological functions of Ets-1 in human hepatocellular carcinoma. In an attempt at elucidation, we examined immunohistochemically hepatocellular carcinoma followed by application of genetic techniques., Methodology: We performed immunohistochemical analysis on tissue from 59 Japanese patients undergoing surgical resection of hepatocellular carcinoma using the antibody against human Ets-1. We compared Ets-1 expression in relation to clinicopathological findings. In situ hybridization and reverse transcription-polymerase chain reaction were also performed to confirm the expression of Ets-1 messenger RNA in hepatocellular carcinoma tissues., Results: In specimens from 59 patients with hepatocellular carcinoma, 41 (70%) showed positive staining for Ets-1 protein. The expression of Ets-1 messenger RNA was also observed in hepatocellular carcinoma tissues by in situ hybridization and reverse transcription-polymerase chain reaction. The expression of Ets-1 correlated with histological differentiation of hepatocellular carcinoma (P < 0.05). Ets-1 was positive in 2 (50%) of the 4 well-differentiated hepatocellular carcinomas and in 28 (64%) of the 44 moderately differentiated hepatocellular carcinomas, whereas all the 11 poorly differentiated hepatocellular carcinomas were positive for Ets-1 staining. Ets-1 protein was expressed more strongly at the peripheral than the central area of the tumor. Otherwise, no particular correlation was evident in terms of clinicopathological factors., Conclusions: We found Ets-1 to be expressed in human hepatocellular carcinoma, particularly at the peripheral area of the tumor. As this expression is linked to cell differentiation, this gene may yield biological information relative to this malignant tumor of the liver.

The purpose of this study was to perform a simple percutaneous transfemoral implantation of a portcatheter access system using a new catheter coating for hepatic artery chemotherapy infusion, and to evaluate the complications of transfemoral infusion port implantation. The methods of treatment for complications were also studied. The port-catheter system was percutaneously implanted via femoral artery access in 180 patients with malignant liver tumors. Blood flow redistribution was performed using embolization coils. An unfixed 5 Fr catheter was placed in a hepatic artery, and connected to a port implanted subcutaneously below the level of the inguinal ligament. The success rate of implantation was 99%. Complications after placement were observed as follows: port system obstruction (9.6%); dislocation of the catheter tip (8.4%); drug toxicity (4.5%); and infection (3.4%). Notable is the avoidance of cerebral infarcts. In 3 of 17 patients with port obstruction, recanalization of the port was achieved. In 11 of 15 patients with catheter dislocation, replacement of the catheter-port system was successful. In 5 patients with hepatic artery occlusion, the replacement of a microcatheter-port access system was achieved, and hepatic artery chemotherapy infusion was resumed. This percutaneous transfemoral implantation of a catheter-port access system would seem to be a very simple and useful method for many clinical doctors, and it may improve the quality of life in patients with an unresectable malignant liver tumor.

A weekly HAI therapy (CPT-11 80 mg, MMC 4 mg, degradable starch microsphere (DSM) 600 mg) was given to a patient with sigmoid colon cancer and multiple liver metastasis (H3) who had been taking tegafur 300 mg/day and 5-FU 750 mg HAI/week, which resulted in PD. This therapy was carried out on an outpatient basis with minimum side effects (< grade 2). After 8 weeks, the tumor marker dropped to one tenth and the liver metastasis decreased in size (PR). The time courses of the concentrations of CPT-11, SN-38 and SN-38G were determined by drawing blood after HAI with or without DSM. The Cmax and AUC inf. of SN-38 at HAI without DSM were 17 ng/ml and 90.55 ng/h/ml, respectively, which was comparable to that at i.v. administration. The Cmax and AUC inf. of SN-38 at HAI with DSM were 12 ng/ml and 129.19 ng/h/ml, respectively, implying that DSM might have an enhancing effect on CPT-11 due to stasis of the hepatic artery that slows the conversion of CPT-11 to SN-38 resulting in a longer existence of SN-38.

Objective: Evaluation of the usefulness of the serial determinations of serum alpha-L-fucosidase (AFU) activity for prediction of the development of hepatocellular carcinoma (HCC) was performed., Methods and Patients: Serum AFU activity was determined monthly for 42 months in 73 patients with liver cirrhosis (LC)., Results: HCC was diagnosed in 27 patients by means of ultrasonography during this observation period. In 23 (85%) of the 27 patients, serum AFU activity was found to exceed 700 nmole/ml/h during the LC stage. HCC developed within a few years in 23 (82%) of 28 LC patients with AFU activity exceeding 700 nmole/ml/h, in contrast, it developed in only 4 (9%) of 45 LC patients with AFU activity below 700 nmole/ml/h. AFU activity was already elevated in 23 (85%) of 27 patients at least 6 months before the detection of HCC by ultrasonography., Conclusion: It is conceivable that the development of HCC can be predicted by means of serial determinations of serum AFU activity in patients with LC.

We investigated the effectiveness of continuous arterial infusion of low-dose CDDP, 5-FU for residual cancer after cytoreductive surgery for advanced hepatocellular carcinoma. Thirty-one patients with unresectable advanced hepatocellular carcinoma were classified into two groups by adjuvant therapy after reduction surgery: 1) Low-dose FP Group: 17 patients; continuous arterial infusion of low-dose CDDP, 5-FU via implanted port system; 2) Conventional group: 8 patients; Lipiodolization (6 cases) and transcatheter arterial embolization (2 cases). The five-year survival rate in the low-dose FP group was 34.8%, the efficacy was 64.7%, CR: 6 (35.3%); PR: 5; NC: 4; PD: 2. Thus, continuous arterial infusion of low-dose CDDP, 5-FU was effective as adjuvant therapy in cytoreductive surgery for advanced hepatocellular carcinoma.

A rare case of malignant lymphoma of the stomach after treatment for hepatocellular carcinoma (HCC) is reported. A 72-year old man presented with a large mass on the right hypochondrium, which was diagnosed as HCC associated with chronic hepatitis C with cirrhosis. The inoperable tumor was treated conservatively with cisplatin, etoposide, carboplatin, and Lipiodol infused into the hepatic artery, together with transcatheter arterial embolization. The patient presented 38 months later with features suggestive of gastric ulceration. Endoscopy and histological examination of biopsy material confirmed the presence of malignant lymphoma of the stomach. He ultimately died as a result of hepatic failure. The clinical presentation suggests that gastric lymphoma was possibly related to the lymphotropic effect of hepatitis C virus (HCV) and exacerbated by intraarterial injection of the cytotoxic drugs.

Twenty five patients with postoperative multiple recurrence and residual hepatocellular carcinoma received continuous arterial infusion of CDDP and 5-FU via implanted reservoir. For the next five days, 10 mg/body of CDDP and 250 mg/body of 5-FU using arterial infusion were administered. It was discontinued for two days as one course, and 4 courses were basally administered. The efficacy rate was 60%, and there were 7 (28%) CR (complete response) cases. The survival rate was 76.0% for 1 year and 36.5% for 3 years, which is a favorable result considering their advanced stage. Thus, this treatment seemed to be effective for multiple hepatocellular carcinoma.

Intra-arterial infusion chemotherapy is commonly used to treat hepatocellular carcinomas (HCC) and metastatic liver cancer after hepatectomy or in unresectable patients, and it has been adopted at Kurume University Hospital as a treatment for HCC. As complications of reservoir implantation have been encountered, the implantation procedure needs improvement. Procedures were compared in a study with 109 patients who were available for follow-up observation among 116 patients who underwent reservoir implantation. Fifty-six of the patients received intraoperative implantation through the gastroduodenal artery (GDA catheterization), 31 received external catheterization (EXT catheterization) and 22 received catheterization using a saphenous vein graft (SVG catheterization). The complication rates were 75.0%, 9.7% and 13.9% and the one-year patencies were 44.1%, 70.6% and 79.4%, respectively. GDA catheterization was no better than the other two procedures and it had a higher incidence of complications and a lower patency. SVG catheterization achieved good patency, although it had a little higher incidence of complications than external catheterization. It was presumed to be a procedure that would ensure reservoir implantation even in patients with a winding or variation of hepatic artery.

The administration of 200 nM K252a to HuH7 suppressed the proliferation of the cells almost completely. The uptake of [3H]thymidine was inhibited, and flow cytometry revealed only one peak at 2C on day 3 after treatment with 100 nM K252a. The expression of proto-oncogene c-myc was not reduced. Despite the blockage at G1, both the size of the cells and the amount of cell protein had increased by 4 times by day 3 after treatment with K252a, while the cells secreted albumin and alpha-fetoprotein into the medium as usual. These results show that K252a can increase the cell size of HuH7 without losing its function by blocking the cell cycle at G1 phase.