[A case of hypovascular acinar cell carcinoma of pancreas, liver metastatic lesions of which showed hypervascular].
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Carcinoma, Acinar Cell↗
Biomedical subjects
K Katayama
Publications and source records attributed to K Katayama.
Factors affecting postoperative prognosis in the solitary-nodule type of hepatocellular carcinoma: experience of 132 cases in our institute.
A retrospective analysis of clinical and pathological factors was performed on 132 surgical cases with solitary-nodule type HCC in our hospital. The overall cancer-free survival rates after 1, 3 and 5 years were 82.2%, 42.3% and 26.5%, respectively. With univariate analysis, the significant prognostic factors for survival were tumor size, cancer cell infiltration of the fibrous capsule of the tumor (fc-inf), invasion into portal vein (vp), and intrahepatic metastasis (im), while significant prognostic factors for non-recurrence were tumor size, fc-inf, vp, im, Edmondson-Steiner's classification and perioperative blood transfusion. With multivariate analysis for recurrence, significant factors were vp, clinical stage (CS), and perioperative blood transfusion. Therefore, prognostic factors for long-term survival in surgical cases of HCC are thought to be good hepatic function, absence of portal invasion, and avoidance of perioperative blood transfusion if possible.
Adult↗
Indications for palliative reduction surgery for hepatocellular carcinoma with multiple intrahepatic metastases.
We evaluated the efficacy of and the indications for palliative reduction surgery as a procedure to improve the prognosis of hepatocellular carcinoma (HCC) patients with multiple intrahepatic metastases. From January 1986 to October 1997, 25 HCC patients with multiple intrahepatic metastases who underwent necessary palliative reduction surgery due to advanced disease, were participated in the study. The 1-, 3-, 5-year survival rates of 25 patients with reduction surgery were 54.7%, 29.9%, 22.4%, respectively. Moreover, the 1-, 3-, 5-year survival rates of patients with some postoperative supplemental treatment were 68.8%, 41.2% and 30.9%, respectively. All 6 patients who had been alive for more than 3 years had had primary tumors with diametric sizes of approximately 5 cm and had undergone, at most, one segmentectomy. These patients received postoperative supplemental treatments. The indication for palliative reduction surgery for HCC patients with multiple intrahepatic metastases was patients with a relatively small primary tumor (around 5 cm) which could be removed by one segmentectomy or less.
Aged↗
Thoracoscopic microwave coagulation therapy for hepatocellular carcinoma.
Thoracoscopic microwave coagulation therapy (MCT) is a new therapeutic approach for hepatocellular carcinoma (HCC) in segments VII and VIII, which allows minimal access to the tumor and complete tumor ablation. In this study, four patients with HCC in segments VII and VIII underwent thoracoscopic MCT as a less invasive therapeutic option due to advanced liver cirrhosis and/or severe complications. Tumor sizes ranged from 15 to 30 mm in diameter and the tumors were well differentiated in 2 patients, moderately in one and poorly in one patient. Microwave irradiation was performed at an 80 W output with a 60-sec duration via a thoracoscopic route and the total duration ranged from 4 to 24 min (mean: 17 min). Patients recovered rapidly to preoperative conditions and no mortality was occurred. Complications were observed in one patient, including pleural effusion and fever elevation, but were cured conservatively. Postoperative computed tomography (CT) showed complete tumor ablation with a cancer-free margin, which is thought to be equivalent to a limited hepatic resection. This preliminary study suggests that thoracoscopic MCT might be a new, less invasive option providing a cure for HCC in segments VII and VIII in patients with advanced liver cirrhosis and severe complications.
Aged↗
A hydrolase enzyme inactivating endogenous ligands for cannabinoid receptors.
Cannabinoids are psychoactive components of marijuana, and bind to specific G protein-coupled receptors in the brain and other mammalian tissues. Anandamide (arachidonoylethanolamide) was discovered as an endogenous agonist for the cannabinoid receptors. Hydrolysis of anandamide to arachidonic acid and ethanolamine results in the loss of its biological activities. The enzyme responsible for this hydrolysis was solubilized, partially purified from the microsomes of porcine brain, and referred to as anandamide amidohydrolase. In addition to the anandamide hydrolysis, the enzyme preparation catalyzed anandamide synthesis by the condensation of arachidonic acid with ethanolamine. Several lines of enzymological evidence suggested that a single enzyme catalyzes both the hydrolysis and synthesis of anandamide. This reversibility was confirmed by the use of a recombinant enzyme of rat liver overexpressed in COS-7 cells. However, in consideration of the high Km value for ethanolamine as a substrate for the anandamide synthesis, the enzyme was presumed to act as a hydrolase rather than a synthase under physiological conditions. The recombinant enzyme acted not only as an amidase hydrolyzing anandamide and other fatty acid amides but also as an esterase hydrolyzing methyl ester of arachidonic acid. 2-Arachidonoylglycerol, which was found recently to be another endogenous ligand, was also efficiently hydrolyzed by the esterase activity of the same enzyme. The anandamide hydrolase and synthase activities were detected in a variety of rat organs, and liver showed by far the highest activities. A high anandamide hydrolase activity was also detected in small intestine but only after the homogenate was precipitated with acetone to remove endogenous lipids inhibiting the enzyme activity. The distribution of mRNA of the enzyme was in agreement with that of the enzyme activity.
Amidohydrolases↗
Hepatic resection for cavernous hemangiomas of the liver.
In this report, we evaluate the indications of, and present our recent strategy for, cavernous hemangioma of the liver. Seven patients with cavernous hemangiomas of the liver, who underwent hepatic resection were enrolled in this study. The lesions were located in the right lobe in 3 patients, the left lobe in 2, and in both the right and left lobes in 2. The longest diameter of the lesions ranged from 1.4 to 14.5 cm (mean, 8.2 cm). The indications for hepatic resection were symptomatic lesions in 3 patients, lesions suspected to be hepatocellular carcinoma in 2, and symptomatic and growing lesions during follow-up in 2. Right lobectomy was performed in 2 patients, left lobectomy with caudate lobectomy in 1 patient, and minor hepatic resection in the other 4 patients. One of the patients who underwent minor hepatic resection had recently received laparoscopy-assisted hepatic resection and one of the three patients who received transfusion during surgery was given an autotransfusion. There were no mortality, and morbidity was minimal. In conclusion, hepatic resection, including laparoscopy-assisted procedures, was considered a safe treatment. Hepatic resection for cavernous hemangioma should be performed only in patients with moderate to severe symptoms, complicated lesions or both, because most benign lesions have a good natural course. Furthermore, in the future, less invasive surgical procedures should be used whenever possible to treat these benign liver tumors.
Digestive System Surgical Procedures↗
Percutaneous microwave coagulation therapy for hepatocellular carcinoma.
We evaluated the efficacy of percutaneous microwave coagulation therapy (PMCT) as compared with hepatectomy in 19 patients with hepatocellular carcinoma (HCC). In 6 patients with tumors more than 3 cm in diameter, coagulation was inadequate after a single session of PMCT. Patients with multiple tumors had recurrence within 1 year. For single tumors 3 cm or less in diameter, the therapeutic effectiveness of PMCT was comparable to that of hepatectomy in cumulative survival and cancer-free survival rates. We conclude that PMCT should be used in the initial treatment of HCC only in patients with single tumors of up to 3 cm in diameter. Surgical removal is recommended for tumors of more than 3 cm in diameter.
Adult↗
A surgically treated long-term survivor of hepatocellular carcinoma with tumor thrombi in the trunk of the portal vein.
Prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombi (TT) in the trunk of the portal vein (PV) has been extremely poor. There have been few reports of long-term survivors with such an advanced condition. In this article, the case of a 62-year-old woman of HCC, who survived for 6 years and 9 months after an operation, with TT in the trunk of the PV is described. The patient not only had a primary tumor of 4 cm in diameter with TT but also multiple intrahepatic metastases in the bilateral lobe of the liver. A palliative lateral segmentectomy with tumor thrombectomy through the incised left first branch of the PV was performed. Moreover, an intraoperative ethanol injection for residual intrahepatic metastatic tumors was performed subsequently. Hepatic arterial infusion of anti-cancer drug with Lipiodol, intraportal continuous infusion of 5-FU and percutaneous ethanol injection therapy were performed suitably during the follow-up periods. The patient survived for 6 years and 9 months after operation and died of hepatic insufficiency with cancer. In this case a patient who suffered from HCC with TT in the trunk of the PV was successfully treated by multimodality procedures including hepatic resection with tumor thrombectomy.
Antineoplastic Agents↗
Laparoscopy-assisted hepatectomy for a large tumor of the liver.
We performed a laparoscopy-assisted hepatectomy on a 52-year-old woman with a large hepatic cavernous hemangioma (longest diameter, 8.5 cm). With the use of Pringle's maneuver, the left lateral segment of the liver was resected with a Cavitron ultrasonic surgical aspirator (CUSA) while lifting the abdominal wall. Postoperative hepatic dysfunction was mild and transient, resolving spontaneously early after surgery. We intend to expand the indications of this minimally invasive procedure for hepatic resection.
Female↗
Distribution of anandamide amidohydrolase in rat tissues with special reference to small intestine.
Anandamide (arachidonylethanolamide), an endogenous ligand for cannabinoid receptors, is hydrolyzed by an amidohydrolase and its biological activity is lost. Previously, we partially purified the enzyme from porcine brain and anandamide synthesis by its reverse reaction was proposed (Ueda et al., (1995) J. Biol. Chem. 270, 23823-23827). The anandamide hydrolase and synthase activities were examined with various rat tissues. Rat liver showed the highest specific activities (4.4 +/- 0.3 and 4.5 +/- 0.5 nmol/min/mg protein) for the hydrolase and synthase, respectively. In most other tissues such as brain, testis and parotid gland, the ratio of synthase/hydrolase activity was 0.7-1.6. However, small intestine showed a relatively high synthase/hydrolase ratio of about 5.0 (1.0 +/- 0.1 and 0.2 +/- 0.1 nmol/min/mg protein). When a homogenate of small intestine was subjected to acetone extraction to remove lipids, a higher hydrolase activity was found (2.0 +/- 0.2 nmol/min/mg protein). Furthermore, Northern blotting detected an intense mRNA band of anandamide hydrolase in small intestine as well as liver and brain. These results demonstrated for the first time a high content of anandamide hydrolase in small intestine.
Acetone↗
A novel type of calcium channel sensitive to omega-agatoxin-TK in cultured rat cerebral cortical neurons.
We characterized the electrophysiological properties of calcium channels in cultured rat cerebral cortical neurons using omega-agatoxin-TK (omega-Aga-TK) by a patch-clamp technique. Two types of slowly inactivating calcium channels sensitive to omega-Aga-TK were detected. The first type showed high sensitivity to omega-Aga-TK and low recovery from the omega-Aga-TK-induced blockade during washout, corresponding to the P-type channel. The second type showed low sensitivity to omega-Aga-TK and high recovery, resembling the Q-type channel, although it was distinct from the Q-type in terms of slower inactivation kinetics. We designate this channel as Q(L)-type (long-lasting Q channel). The omega-Aga-TK-sensitive calcium channels involved in the glutamatergic synaptic transmission were also divided into two types based on the sensitivity to omega-Aga-TK and reversibility of omega-Aga-TK-induced blockade. We conclude that the Q(L)-type is a novel type of channel, and that both P-type and Q(L)-type channels play a significant role in the cerebral cortical synaptic transmission.
Agatoxins↗
Simultaneous quantitative determination method for sphingolipid metabolites by liquid chromatography/ionspray ionization tandem mass spectrometry.
Sphingolipid metabolites ceramide, sphingomyelin, sphingosine, psycosine, sphingosylphosphorylcholine, and dimethylsphingosine were separated and simulataneously quantitated by liquid chromatography/ionspray ionization tandem mass spectrometry (LC/MS/ MS). The use of glassware throughout minimized losses due to adsorption and the pretreatment of this method consisted of simple liquid-liquid extraction procedure with a mixture of chloroform and methanol. After separation on a short C18 silica column eluted in a gradient mode, the metabolites were detected by MS/ MS. This assay allows simultaneously quantification of these metabolites over a range of at least 0.1 to 100 ng/ 10(6) cells. The LC/MS/MS analyses took 10 to 15 min per sample and we could examine up to 50 samples per day. We also detected endogenous sphingosine 1-phosphate in HL-60 cells. The utility of the method was demonstrated by examining changes in metabolites levels in HL-60 cells after treatment with sphingomyelinase. It was found that sphingomyelinase from Bacillus cereus may have selectivity for acyl chain length.
Ceramides↗
B7/BB-1 expression and hepatitis activity in liver tissues of patients with chronic hepatitis C.
Cytotoxic T lymphocytes (CTL) are closely related to the mechanism of liver injury in chronic viral hepatitis. Recently, it has been suggested that antigen-specific T cell activation requires both presentation of antigen by major histocompatibility complex (MHC) molecules and the delivery of costimulatory signals. Such signals are provided by B7/BB-1, one of the most important accessory molecules, sufficient for causing antigen-specific MHC-restricted T cell activation. To evaluate the role of B7/BB-1 in chronic hepatitis C, we immunohistochemically studied its expression in liver tissues obtained from 61 patients with hepatitis C virus (HCV) infection and compared them based on hepatitis activity. In HCV-infected liver, B7/BB-1 was strongly expressed in the cytoplasm of hepatocytes. B7/BB-1-positive cells accompanied liver-infiltrating lymphocytes and were mainly detected in the periportal region. B7/BB-1 expression was closely correlated with the activity of viral hepatitis as evaluated from scores of periportal or intralobular inflammation and necrosis, or serum alanine transferase (ALT) levels. Further study by immunostaining with anti-HCV core and anti-human leukocyte antigen (HLA) class I antibody showed B7/BB-1 positive cells near HCV core antigen- and HLA class I-positive cells, with B7/BB-1-positive cells mostly included among HLA class I-positive cells. These findings suggested that B7/BB-1 expression by hepatocytes may be induced by HCV infection and may trigger generation and activation of CTL, which may cause damage to HCV-infected HLA class I-expressing hepatocytes.
Adult↗
Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human hepatocellular carcinoma.
Costimulation mediated by costimulatory molecules, such as B7-1 and B7-2, which are ligands for the CD28/cytolytic T lymphocyte associated antigen (CTLA)-4 counter-receptor, plays an important role in the induction of T cell-mediated antitumor immunity. We investigated the expressions of B7-1, B7-2, and human leukocyte antigen (HLA) class I in seven human hepatocellular carcinoma (HCC) cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis. RT-PCR showed that all these human HCC cell lines were positive for B7-1 and B7-2 at the messenger RNA (mRNA) level. Flow cytometric analysis revealed that they all expressed B7-1, B7-2, and HLA class I on the cell surface. However, the expression levels of B7-1 and B7-2 were very low whereas those of HLA class I were high. B7-1 and B7-2 expression could be increased by treatment with interferon alpha and interferon gamma in a dose-dependent manner, although the expression levels of B7-1 and B7-2 after interferon treatment remained low. By transfecting Hep3B cells with a plasmid containing human B7-1 complementary cDNA (cDNA), we were able to establish Hep3B cell lines strongly expressing B7-1. From mixed lymphocytes and tumor cultures analysis, the primary cytolytic activity against parental Hep3B cells could be induced effectively by B71-transfected Hep3B cells. These findings suggested that B7-1 gene transfer is the best way to induce strong expression of this molecule and this might be useful for immuno-gene therapy against human HCC.
Antigens, CD↗
New variant groups identified from HGV isolates.
We have determined the primary sequence of the 5' noncoding region (5' NCR) and putative helicase regions (NS-3) of hepatitis G virus (HGV) and GB virus C (GBV-C) that were isolated in Japan from suspected cases of nonA-nonB and/or nonA-nonB-nonC viral hepatitis by using RT-PCR, and we compared the newly isolated sequences with three established isolates. The addition of a "G" residue was found at the 5' terminus of all 8 Japanese isolates. These isolates were more clearly distinguished from the prototype viruses by comparison with the 5' NCR sequence than by comparison with the NS-3 region. Our results suggested that at least three distinct genomic variants of HGV exist. Genotyping of HGV by using RT-PCR based on the sequence of the 5' NCR seems highly feasible.
Base Sequence↗
Disease stage of chronic hepatitis C assessed by both peritoneoscopic and histologic findings and its relationship with response to interferon therapy.
BACKGROUND: Disease stage in patients with chronic hepatitis C was assessed by both peritoneoscopy and histology and correlated with responses to interferon therapy. METHODS: The subjects were 105 patients with chronic hepatitis C treated with interferon who were classified into 28 sustained responders, 34 transient responders, and 43 nonresponders according to alanine aminotransferase normalization. The influence of various patient's characteristics on responses to interferon therapy was investigated by multivariate analysis. RESULTS: Patients were categorized into 21 patients who exhibited a "smooth liver" on peritoneoscopy and did not demonstrate histologic bridging fibrosis (group I) and 84 patients who exhibited a "granular" or "nodular liver" on peritoneoscopy and/or had histologic bridging fibrosis (group II). Multivariate analysis showed that genotype 2a/2b (p = .0002), low viremia (p = .0048), and early disease stage (group I) (p = .0290) were significant independent factors contributing to sustained response, and that early disease stage (group I) (p = .0010) and genotype 2a/2b (p = .0085) were those contributing to sustained or transient response. Neither peritoneoscopic nor histologic findings alone were a significant factor influencing responses to interferon therapy. CONCLUSION: Disease stage assessed by both peritoneoscopic and histologic findings may serve as a reliable marker for predicting responses to interferon therapy in chronic hepatitis C.
Adult↗
Circulating matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as serum markers of fibrosis in patients with chronic hepatitis C. Relationship to interferon response.
BACKGROUND/AIMS/METHODS: The imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is considered to be an important determinant of extracellular matrix deposition and breakdown. We measured serum MMP-1, MMP-2, TIMP-1 and TIMP-2 levels using the respective one-step sandwich enzyme immunoassays in 98 patients with chronic hepatitis C treated with interferon beta to examine their clinical significance for assessment of liver histology and to determine whether they can be useful as predictors of the interferon response. RESULTS: Serum TIMP-1 levels showed a positive correlation with the degree of fibrosis (r(s)=0.30, p= 0.004). Serum MMP-2 levels revealed positive relationships with the degree of periportal necrosis (r(s)= 0.32, p=0.002), the degree of fibrosis (r(s)=0.26, p= 0.01) and total score of histological activity index (r(s)=0.24, p=0.02). Serum MMP-2 levels were significantly higher in patients with no response than in those with sustained and transient response (p<0.01 and p<0.05, respectively), while serum MMP-1 levels did not differ among the three groups. Compared with the levels in sustained responders, the total amounts of serum TIMP-1 were significantly lower in transient responders and non-responders (p<0.01 and p<0.001, respectively). As for serum TIMP-2 levels, a significant decrease was found in transient responders and non-responders (p<0.01). The ratios of serum MMP-2 to TIMP-1 levels were significantly higher in transient responders and non-responders than in sustained responders (p<0.001, respectively) even when HCV RNA levels were low in patients with HCV genome subtype 1b or when the HCV genome subtype was 2a or 2b. Sustained response was never found in type 1b patients with ratios of serum MMP-2 to TIMP-1 levels of over 6.0. In logistic multivariate regression analysis, the ratios of serum MMP-2 to TIMP-1 level (p=0.0001), HCV genome subtype (p=0.005) and serum TIMP-2 level (p=0.03) were the independent predictors for sustained response, while serum MMP-2 level (p=0.0006) was the only predictor for no response. CONCLUSIONS: Serum MMP-2 and TIMP-1 levels might be useful for estimating the degree of liver fibrosis. The ratio of serum MMP-2 to TIMP-1 levels may serve as a new predictor of interferon response in patients with chronic hepatitis C.
Alanine Transaminase↗
Neutralization of transforming growth factor beta 1 augments hepatitis C virus-specific cytotoxic T lymphocyte induction in vitro.
In hepatitis C virus (HCV) infection, TGF-beta 1 is upregulated in the liver and may be involved in the pathogenesis of chronic liver disease. TGF-beta 1 is also produced by activated T cells and acts as a potent immunosuppressor. The aim of this study was to investigate the roles of TGF-beta 1 in HCV-specific cytotoxic T lymphocyte (CTL) induction and enhance their killer activity by TGF-beta 1 modulation. We generated anti-HCV CTL from peripheral blood mononuclear cells from HLA-A2 patients under stimulation with the HCV-core peptide having the HLA-A2.1 binding motif. The lytic activities of CTL or precursor frequency (CTLpf) generated with or without anti-TGF-beta antibody were compared. To optimize the IL-2 dose for CTL induction, low (50 U/ml) and high (500 U/ml) doses were tested and the lytic activities were compared. TGF-beta 1 amounts in the supernatants were assessed by enzyme-linked immunosorbent assay and by their growth inhibitory effect on mink lung epithelial cells. CTL activity was enhanced by anti-TGF-beta antibody in a dose-dependent manner but CTLpf did not significantly change. A high dose of IL-2 reduced the activity to 45% of that observed with a low dose, whereas TGF-beta 1 increased as the dose of IL-2 increased. Exogenous IL-10 reversed the inhibitory effect of a high dose of IL-2 on the killing activity by reducing TGF-beta 1 mRNA expression in T cells and its production. These results demonstrated that endogenous TGF-beta 1 is an autocrine suppressor in CTL induction in vitro. Therefore, the blockade of endogenous TGF-beta 1 could enhance the killing potential of anti-HCV CTL.
Adult↗