IV胆道発癌 1.全国集計からみた発癌頻度と特徴.

IV胆道発癌 1.全国集計からみた発癌頻度と特徴.


V治療 2.全国集計からみた外科治療

V治療 2.全国集計からみた外科治療


臓器部位別の治療戦略 肝がんー手術とインターベンション, PEIT, RFA, TAEなどー.


腹腔鏡下肝切除術 4．術中・術後のトラブルと回避法 ガス塞栓

腹腔鏡下肝切除術 4．術中・術後のトラブルと回避法 ガス塞栓


Ⅱ 基本手技 3.肝臓ハンギング法，肝脱転 肝胆膵高難度外科手術

Ⅱ 基本手技 3.肝臓ハンギング法，肝脱転 肝胆膵高難度外科手術


Surgical outcome of patients with hepatocellular carcinoma originating in the caudate lobe

Hepatocellular carcinoma (HCC) originating in the caudate lobe is rare, and the treatment for this type of carcinoma is difficult because of its unique anatomic location. This retrospective study assessed the surgical outcome of patients with caudate lobe HCC. There were 20 cases of HCC originating in the caudate lobe among 435 patients with primary HCC who underwent hepatic resection in our department from 1990 to 2002. The caudate tumors were located in the Spiegel lobe in 3 patients, the paracaval portion in 15 patients, and the caudate process in 2 patients. Surgical procedures consisted of limited resection of the caudate lobe in 6 patients and extended caudate lobectomy in 14 patients. Recurrence was recognized in 12 patients, including 8 patients with multiple intrahepatic recurrences, 1 with peritoneal dissemination, and 1 with lymph node metastasis. There was no significant difference in postoperative survival rate between patients who underwent limited resection of the caudate lobe and those who underwent extended caudate lobectomy. Compared with 415 patients with HCC originating in other locations, the 20 patients with caudate lobe HCC showed significantly more intraoperative blood loss (P<.05), longer operation time (P<.0001), and more postoperative complications (P<.005). Intrahepatic recurrence was more frequent in the caudate lobe HCC compared with HCC originating in other locations (40% vs 17.6%; P<.05). There was a significantly poor survival rate in the postoperative patients with caudate HCC (25.9% vs 54.1% for five-year survival; P=.01). Intrahepatic multiple recurrences were frequently recognized in the patients with caudate lobe HCC, indicating no significance for extended caudate lobectomy. Because of the relatively poor prognosis in patients with caudate lobe HCC, adjuvant therapy combined with surgical operation should be considered.


Extended lobectomy for procurement of the left lobe with caudate lobe for living-related liver transplantation

Liver transplantation from living-related donors has been established for end-stage liver disease. In adult cases, the left lobe with a caudate lobe was transplanted in order to increase the graft volume. However, the procurement operation should be less invasive for the donor. In this article, we represent our technique by which the blood loss can be reduced during the harvesting operation. The technique was used to improve the extended left lobectomy for the procurement in 27 patients between May 1997 and December 1999 at Kyushu University Hospital. The groups included the following: 1) Procurement operation of the extended left lobe with caudate (n=9), 2) without caudate (n=18). The detailed record during the operation showed that the mean blood loss and the amount for the group with caudate was significantly smaller than that in the group without caudate. To reduce the blood loss during the procurement operation, we continue to use this technique in the living-related donors for adult recipients.


A novel intrahepatic arterial chemotherapy after radical resection for advanced hepatocellular carcinoma

Advanced hepatocellular carcinoma (HCC) with portal vein invasion and/or intrahepatic metastasis has an unfavorable prognosis even after radical hepatic resection. The aim of this study was to evaluate the effectiveness of a novel postoperative adjuvant chemotherapy given through the hepatic artery and based on biochemical modulation using cisplatin (CDDP) and 5-fluorouracil (5-FU). Fifteen patients with advanced HCC with portal vein invasion into the main trunk and/or intrahepatic metastases of more than 3 segments were included in this study. After radical hepatic resection, the patients were divided to two groups: the adjuvant chemotherapy group (n=7) given the novel arterial infusion regimen with CDDP and 5-FU, and the control group (n=8) given no adjuvant chemotherapy. Three-year survival rate of the adjuvant chemotherapy group tended to be significantly longer compared to that for the control group (p < 0.05). Most of the tumor recurrence was in the remnant liver, 5 cases in both of the groups. Significant difference of the recurrence patterns was recognized, rather than difference of the disease-free survival rate between the two groups. All of the intrahepatic recurrences are multiple in the control group, but in the adjuvant chemotherapy group, 2 cases of the recurrences showed a localized tumor surgically resected. It is noteworthy that the occurrence of multiple recurrence was significantly later in the adjuvant chemotherapy group compared to the control group (18.9 months vs. 6.5 months; p<0.05). Our data suggest that this novel adjuvant chemotherapy can improve the postoperative prognosis of patients with the advanced HCC.


Detection of combined hepatocellular and cholangiocarcinomas on enhanced CT: comparison with histologic findings


The newly established human hepatocyte cell line: application for the bioartificial liver

European Association for the Study of the Liver

Human hepatocyte cell lines are reported to lose many of their biochemical functions in a hybrid artificial liver support system (HALSS). Differentiation therapy is useful to up-regulate liver function. The human hepatoblastoma cell line HepG2 was transfected with HSV/tk gene. Albumin synthesis and ammonia removal activity were evaluated when HepG2/tk was cultured with histone deacetylase inhibitor (FR228) and peroxisome proliferator activated receptor-gamma ligand (pioglitazone). To investigate the function of HepG2/tk in vivo, cell transplantation for 90% hepatectonized rats was conducted. We established stable cell lines which expressed HSV/tk and were sensitive to gancyclovir in vitro and in vivo. Both albumin synthesis rate and ammonia removal rate improved for HepG2/tk incubated with FR228 and pioglitazone for 3 days, which induced nuclear transport of p21. Rats with intrasplenic injection of HepG2/tk precultured for 3 days with FR228 and pioglitazone survived significantly longer than the control rats. The ammonia and total bilirubin concentrations were significantly lower in the test group than in the control group. The injection of gancyclovir inhibited the prolonged survival of the rats with precultured HepG2/tk. HepG2/tk is safe as well as enhancing high levels of liver function. It will be a potential cell source for HALLS in the future.


Role of tissue trace elements in liver cancers and non-cancerous liver parenchyma

The role of trace elements in liver fibrosis, carcinogenesis and progression of hepatocellular carcinoma (HCC) has not yet been clarified. The aim of this study is to analyze the characteristics of trace elements in liver cancers and non-cancerous liver and to discuss their role in hepatic fibrosis, hepatocarcinogenesis and progression of HCC. The amount of zinc (Zn), iron (Fe), and copper (Cu) in 20 HCCs, 2 cholangiocellular carcinomas (CCC), 7 metastatic liver cancers (Meta) and their non-tumorous liver parenchyma were measured using an atomic absorption spectrophotometer. The amounts of Zn and Fe in non-tumorous liver parenchyma were reduced by liver fibrosis, and the amounts were lower in HCC tissue compared to non-tumorous liver parenchyma. The amounts of Zn and Cu were higher in HCC than the amounts found in CCC and Meta. The amount of Zn in HCC tissue decreased, but the amount of Fe increased in tumors more than 4cm in diameter. These results suggest that the decrease in the amount of Zn and Fe found in non-tumorous liver parenchyma correlates with liver fibrosis leading to cirrhosis and hepatocarcinogenesis. Also that decreases in Zn and increases of Fe in HCC tissue correlates with HCC tumor progression.


Detecting postsurgical recurrent hepatocellular carcinoma with multiphasic helical computed tomography: intrahepatic metastasis or multicentric occurrence?

The aim of this study was to assess the computed tomography (CT) patterns of postoperative recurrent hepatocellular carcinoma (HCC). Of 84 patients with histologically proven HCC by hepatectomies, multiphasic helical CT demonstrated 54 HCC lesions of intrahepatic recurrence in 31 (37%) patients. The initial and final appearances of HCC on hepatic arterial phase images were retrospectively determined by the serial CT scans, which were compared with appearances of primary HCC. The initial appearances of 54 recurrent HCCs were identical to the appearances of primary HCC in 41 (76%) lesions. Serial changes from the initial appearance to the final appearance of recurrent HCC were observed in 10 (42%) of 24 lesions. The 13 discordant lesions and the 10 lesions with altered lesion vascularity in our series implied that at least 43% were of multicentric occurrence. More than 40% of postoperative recurrent HCCs show intranodular hemodynamic changes. The incompatibility between CT findings of primary and recurrent HCCs implies that these tumors contain nodules of multicentric occurrence.


Selenoprotein P, as a predictor for evaluating gemcitabine resistance in human pancreatic cancer cells

Gemcitabine is a new standard chemotherapeutic agent used in the treatment of pancreatic cancer, but the mechanisms of gemcitabine sensitivity are still controversial. In our study to determine a mechanism that regulates gemcitabine sensitivity, we carried out molecular analysis on the susceptibility of the pancreatic cancer cells. Using a gemcitabine-sensitive pancreatic cancer cell line KLM1, we established a resistant cell line KLM1-R exhibiting a 20-fold IC50-value (the concentration of gemcitabine causing 50% growth inhibition). Microarray analysis of genes showed specific expression of selenoprotein P, one of the anti-oxidants, in the KLM1-R cell line but not in the KLM1 cell line. Administration of selenoprotein P inhibited the gemcitabine-induced cytotoxicity in the pancreatic cell lines. The levels of intracellular reactive oxygen species (ROS) were increased in the KLM1 cells by gemcitabine, but selenoprotein P suppressed the gemcitabine-induced ROS levels. Furthermore interferon-gamma suppressed the expression of selenoprotein P mRNA and increased intracellular ROS level, leading to the recovery of the gemcitabine sensitivity in KLM1-R. These results suggest a novel mechanism that selenoprotein P reduces the intracellular ROS levels, resulting in the insusceptibility to gemcitabine.


Change in alpha glutathione s-transferase levels during liver resection

Alpha-glutathione s-transferase (GST) is a 50,000-kDa cytosol protein of the hepatocytes. It comprises 5% of the soluble protein of hepatocytes and is readily released in response to injury. Its half-life time is 60 minutes (AST: 47 hrs, ALT: 22 hrs). The aim of this study is to clarify the usefulness of GST measurement during liver resection. We obtained data from 26 patients undergoing liver resection and compared GST levels with AST and ALT levels. Patients included 15 hepatocellular carcinoma, 5 cholangiocellular carcinoma and 6 metastatic cancers (4: colon, 2: stomach). We performed lobectomy for 11, segmentectomy for 5 and partial resection for 10 patients. From these patients, blood samples were collected before surgery, beginning of resection, end of resection, 15, 30, 60 min after resection, end of surgery, 1, 3, 6, 12, 24 hr after operation and 2, 3, 4, 5, 6, 7, 10, 14 postoperative days (POD). GST (Biotrin, Ireland) levels in the serum samples were determined by an ELISA. We also measured AST, ALT levels from the same set of samples. At the end of resection, GST showed highest level and quickly decreased at 1 hr after operation. On the other hand, AST and ALT showed peak levels at 12 hr after operation. Our findings suggest that perioperative GST measurement may be a sensitive and useful marker to evaluate liver function after liver resection.


Preoperative hyaluronic acid measurement to assess the hepatic functional reserve

With liver surgery, preoperative assessment of the hepatic functional reserve is important for estimating the extent of hepatectomy. Hyaluronic acid (HA) is specifically cleared and metabolized by endothelial cells in the liver. Its half-life time is 2-5 min and HA might be a sensitive liver function marker. We obtained data from 44 patients with liver tumor undergoing liver resection. We studied 44 liver resected patients. Blood samples were obtained before surgery and HA levels and other liver function markers [type IV collagen (IV), procollagen-III-peptide (PIIIP), lecithin-cholesterol acyltransferase (LCAT), cholinesterase (ChE), albumin (Alb), platelets (Plt), prothrombin time (PT%)] levels in the samples were measured. We also performed indocyanine green retention test and calculate R15% (ICG). HA showed strong positive correlation with ICG, IV and PIIIP, negative correlation with LCAT, ChE, Alb, Plt and PT%. ICG was not correlated with ChE, Plt and PT%. The HA levels and ICG of the patients who had more than 2 segments of the liver resected were below 100 ng/mL and 20%, respectively. In the patients with obstructive jaundice HA levels of the 3 patients with obstructive jaundice who underwent bisegmentectomy were below 100 ng/mL. Our findings suggest that HA is a useful preoperative liver function test as well as ICGR15%. Preoperative HA levels <100 ng/mL and ICGR15% <20% might be helpful indicators for major liver resection. We also recommend that HA measurement for evaluating liver function in the patients with obstructive jaundice ICG is not helpful.


The critical role of Fas-Fas ligand interaction in donor-specific transfusion-induced tolerance to H-Y antigen

Donor-specific transfusion (DST) has been clinically used to enhance the survival of transplanted organs, and it has been shown in mice to induce tolerance to male (H-Y) antigen (Ag). Although the biologic mechanisms that initiate and maintain DST-induced tolerance involve clonal deletion, induction of anergy, and generation of regulatory cells, the molecules essential to tolerance induction are still unclear. In this study, we investigated the role of Fas-FasL interaction in DST-induced tolerance to H-Y Ag. C57BL/6 (B6) or B6-Fas(lpr) (lpr) female mice were intravenously injected with B6, lpr, or B6-FasL(gld) (gld) male spleen cells (SC). B6 male skin grafts, mixed lymphocyte reaction (MLR) assay, and cytotoxicity assay (CTL) were performed 7 days after DST. In some experiments, purified B-cells were used as transfused cells. B6 female mice treated with B6 male SC permanently accepted B6 male skins, whereas untreated B6 or lpr female mice rejected B6 male skins. On the other hand, B6 female mice treated with gld male SC acceleratingly rejected male skin, as did lpr female mice treated with B6 or gld male SC. The recipient mice in the experimental groups, in which DST resulted in the accelerated rejection of the skin grafts, had strong allo-responses to H-Y Ag in MLR and CTL. Further, B6 female mice treated with gld male B-cells acceleratingly rejected male skins, whereas B6 female mice treated with B6 or lpr male B-cells from mice accepted male skins. These findings suggest that the interaction between FasL upon infused SC, especially upon B-cells and Fas in a recipient, is essential in DST-induced tolerance to H-Y Ag.


Clinicopathological correlates of aspartyl (asparaginyl) beta-hydroxylase over-expression in cholangiocarcinoma

International Society for Preventive Oncology (ISPO)

Aspartyl (asparaginyl) beta-hydroxylase (AAH) expression in surgically resected intrahepatic cholangiocarcinoma significantly correlated with tumor size, growth type, differentiation, vascular invasion, and prognosis after surgery. AAH may have a role in regulating invasive or metastatic tumor cell growth of human intrahepatic cholangiocarcinoma. Recent studies demonstrated increased expression of the AAH gene in the majority of cholangiocarcinomas. The present study was undertaken to determine the relationship between high or low levels of AAH expression and the clinical course of intrahepatic cholangiocarcinoma (ICC). AAH expression was examined in 50 surgically resected primary ICCs, 12 samples of normal liver, and 12 cases of primary sclerosing cholangitis (PSC). The sections were evaluated by immunohistochemical staining with the FB-50 monoclonal antibody to human AAH protein. The sections were examined under code and graded for relative levels of AAH immunoreactivity. The results were analyzed with respect to multiple clinical and histopathological variables to determine correlates of AAH expression in ICCs. Forty-six of the 50 (92%) ICCs had AAH immunoreactivity, whereas the 12 normal liver and 12 PSC specimens were AAH negative. In the ICC specimens, the highest levels of AAH immunoreactivity were detected at the infiltrating margins that interfaced with uninvolved liver tissue, and the lowest levels occurred in the central portions of the tumors. Multivariate analysis demonstrated that high levels of AAH expression were correlated with tumor size (P < 0.05), infiltrative growth pattern (P < 0.01), aggressive histological grade (P < 0.01), vascular invasion (P < 0.05), and poor prognosis (P < 0.05). These findings suggest that AAH has an important role in regulating invasive or metastatic tumor cell growth of human ICC, and that high levels of AAH expression correlate with poor prognosis.


Comparison of test-injection method and fixed-time method for depiction of hepatocellular carcinoma using dynamic steady-state free precession magnetic resonance imaging

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). 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. 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). 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.


Muscle-targeted interleukin-12 gene therapy of orthotopic hepatocellular carcinoma in mice using in vivo electrosonoporation

American Association for Cancer Research

We developed a new potent nonviral gene transfer method into mouse muscles in vivo named "electrosonoporation." We tried in this report to treat murine orthotopic hepatocellular carcinoma (HCC) by muscle-targeted mouse interleukin-12 (mIL-12) gene transfer using in vivo electrosonoporation. I.m. administration of the mIL-12 gene with electrosonoporation elevated serum IL-12 and IFN-gamma and significantly prolonged the survival periods with both growth inhibition of orthotopic HCC and inhibition of spontaneous lung metastasis. The IL-12 gene therapy reduced the number of microvessels and induced more Mac-1-positive cells into HCC. These results show that muscle-targeted mIL-12 gene therapy for orthotopic HCC using in vivo electrosonoporation is very efficient and is thus promising for further clinical trial.


Aberrant expression of laminin gamma 2 chain and its prognostic significance in intrahepatic cholangiocarcinoma according to growth morphology

United States and Canadian Academy of Pathology

Laminin gamma 2 chain is an extracellular matrix protein that plays an important role in cell migration and tumor invasion. We report altered expression and characteristic localization of this chain in a series of 105 cases of intrahepatic cholangiocarcinomas examined immunohistochemically. All tumors were grossly classified into the following three types: intraductal growth type (n=9), periductal infiltrating type (n=8) and mass-forming type (n=88). The tumors exhibited three distinct staining types: basement membrane staining, cytoplasmic staining and stromal staining. The basement membranous staining of laminin gamma 2 chain was more frequent in biliary dysplasia, intraductal growth and periductal infiltrating type than in mass-forming type. The cytoplasmic staining of carcinoma cells was observed especially at the cancer-stromal interface or at the invasive front of tumors. Stromal staining of laminin gamma 2 chain was essentially localized in the stroma around cancer cells at the invasive area, and the expression was significantly correlated with tumor aggressive factors and a poor prognosis in patients with intrahepatic cholangiocarcinoma. We conclude that laminin gamma 2 chain exhibits aberrant expression in a stepwise manner through different aggressive stages of tumor progression.


The role of heat shock protein 27 expression in hepatocellular carcinoma in Japan: special reference to the difference between hepatitis B and C

International Association for the Study of the Liver

A recent report showed that heat shock protein (HSP)-27 expression was related to histological grade and survival of patients with hepatocellular carcinoma (HCC). The aim of this study was to examine the effect of expression of HSP-27 on clinicopathological variables in Japanese patients with HCC. An immunohistochemical study for HSP-27 was performed on 60 HCC cases using a monoclonal anti-HSP-27 antibody. We divided 60 patients into two groups, patients with a low expression of HSP-27 (n = 34) and those with a high expression of HSP-27 (n = 26). Forty patients tested positive for the hepatitis C virus (HCV) antibody and 20 tested positive for the hepatitis B surface antigen. There appeared to be no relationship between HSP expression and clinicopathologic factors and no differences were observed between the high expression group and the low expression group. In the hepatitis B virus (HBV) group (n = 20), HSP-27 expression correlated significantly with prognosis, disease-free survival (DFS) and overall survival. High expression was significantly associated with poor prognosis in the HBV group. In contrast, patients with a high expression tended to have a good prognosis in the HCV group (n = 40): DFS and overall survival. This study showed the possibility that HSP-27 plays different roles in HBV- and HCV-associated HCCs.


Effect of dietary conjugated linoleic acid on liver regeneration after a partial hepatectomy in rats

We examined the effect of dietary conjugated linoleic acid (CLA) on liver regeneration after a partial hepatectomy (PH) in Sprague-Dawley rats. PH was performed on rats fed a 0 or 1 wt.% CLA diet for 3 wk. Average liver weight in the CLA fed rat population was heavier than the control rat population at the time of PH and 1-d after PH. Conversely. CLA fed rats' liver weight was significantly lower than control rats at 7-d after PH. This suggests that dietary CLA reduced liver weight gain after PH. Dietary CLA did not affect serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) activities. However. CLA significantly reduced serum albumin levels at 1-d but not at 7-d after PH. 5-Bromo- and 5-iododeoxyuridine incorporation into hepatocytes 1-d post PH was lower in the CLA group. In conclusion, the data suggests that dietary CLA inhibits DNA synthesis after PH, which results in hepatocyte proliferation inhibition.


Decreased expression of osteopontin is related to tumor aggressiveness and clinical outcome of intrahepatic cholangiocarcinoma


コンセンサス2004 肝疾患 治療 --- 第3章 肝細胞癌 生体/脳死肝移植

コンセンサス2004 肝疾患 治療 --- 第3章 肝細胞癌 生体/脳死肝移植

株式会社 アークメディア


Characteristic Gene Expression Induced by Polyurethane Foam/Spheroid Culture of Hepatoma Cell Line, Hep G2 as A Promising Cell Source for Bioartificial Liver


cDNA microarray analysis in hepatocyte differentiation in Huh 7 cells

The risk of xenozoonosis infections poses the greatest obstacle against the clinical application of a hybrid artificial liver support system (HALSS). Primary human hepatocytes are an ideal source for HALSS, but the shortage of human livers available for hepatocyte isolation limits this modality. To resolve this issue, we previously demonstrated the upregulation of hepatocyte-specific function by spheroid formation in polyurethane foam and by culturing with the histone deacetylase inhibitor, trichostatin A (TSA), in a human hepatoma cell line (Huh 7). In this article we analyze the gene expression profile using cDNA microarray (1281 genes) in spheroid formation or culturing with TSA in Huh 7 to determine the target genes in hepatocyte differentiation. In both the spheroid formation and in the culture with TSA, the Oct-3/4 transcription factor was upregulated more thantwofold, while the early growth response-1 (EGR-1) transactivator was downregulated less than 0.5-fold. These results indicate that expressions of Oct-3/4 and EGR-1 may be key factors in the induction of hepatocyte differentiation in Huh 7.


Genetic polymorphism at the 5' regulatory region of multidrug resistance 1 (MDR1) and its association with interindividual variation of expression level in the colon

The multidrug resistance 1 (MDR1) is a key molecule in determining not only the resistance of cancer cells to anticancer agents but also the disposition of a variety of drugs in intestinal and other tissues. However, the mechanism underlying interindividual variations in levels of MDR1 activity and expression in various tissues remains unclear. We analyzed the nucleotide sequence polymorphisms in the 5' upstream regulatory region of the gene spanning 4 kb from the transcriptional start site of MDR1 and tried to identify any associations between polymorphisms and MDR1 expression. Within that region, we identified eight single nucleotide polymorphisms (SNPs) in the region in the Japanese population. Of the SNPs identified, -2410T>C, -1910T>C, and 692T>C were in perfect linkage disequilibrium. In normal colorectal mucosa, diplotypes at the region showed more significant association with the expression level of MDR1 mRNA than each SNP did. In an in vitro reporter assay, transcription activity of the minor-type construct carrying haplotypes 2 and 3 was significantly lower than that of the major-type construct carrying haplotype 1. We next identified two DNA binding proteins: one protein bound to the nucleotide sequence carrying -692T but not to that carrying -692C and another bound to the nucleotide sequence carrying -2352G but three times weaker than that carrying -2352A. This suggested the significance of SNP at -692 and -2352 of MDR1 in variable expression in the colon interindividually. This is the first report connecting SNPs and interindividual variety of MDR1 expression rationally.


Angiopoietin switching regulates angiogenesis and progression of human hepatocellular carcinoma

BMJ Publishing Group Ltd & Association of Clinical Pathologists

Aim: Angiopoietin 1 (Ang-1) and its antagonist, angiopoietin 2 (Ang-2), are novel ligands that regulate the Tie2 receptor. The Ang-2 gene is upregulated in the hypervascular type of human hepatocellular carcinoma (HCC). To gain a better understanding of the role of the Ang-Tie2 system in HCC the expression of these genes was investigated in a series of human HCCs. The expression of the angiopoietin and Tie2 proteins was investigated in nine normal liver tissues and 52 surgically resected HCCs. In addition, the effects of hypoxic stimuli on Ang-1, Ang-2, vascular endothelial growth factor (VEGF), and erythropoietin (EPO) expression was investigated in Hep3B cells. Ang-1, rather than Ang-2, was more frequently expressed in the normal liver. Ang-1 was expressed in 68% of HCCs, whereas Ang-2 was expressed in 81%, and was significantly higher in poorly differentiated HCCs characterised by high vascularity (p = 0.02), and in tumours with a peliotic change (p = 0.02). Strong expression of Tie2 was seen in tumour vessels in accordance with Ang-2 expression. In Hep3B cells, hypoxic stimuli upregulated VEGF and EPO, but not Ang-1 or Ang-2. These data support the evidence that the reversal of Ang-1 and Ang-2 expression plays an important role in the angiogenic and dedifferentiation processes in HCC. The hypoxic stimuli were not responsible for Ang-2 upregulation, unlike that of VEGF, in human HCC cells.


Hepatocyte growth factor and transforming growth factor beta1 contribute to regeneration of small-for-size liver graft immediately after transplantation

Although the ability of the liver to regenerate to a predetermined size after resection made adult-to-adult living donor liver transplantation (LDLT) possible, there is little information regarding the growth regulatory mechanism for a small-for-size graft. Forty-one cases of LDLT were divided into two groups by graft volume to standard liver volume ratio (GV/SLV); small graft group (Group S, GV/SLV<40%, n=16) and non-small graft group (Group NS, GV/SLV>40%, n=25). The regeneration rate (GV at 1 week/harvested GV) and serum levels of hepatocyte growth factor (HGF), transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta1 (TGF-beta1) were compared between two groups. The regeneration rates in Group S were significantly higher than that of Group NS (217+/-12% and 178+/-10%, respectively, P<0.01). The serum HGF levels of Group S were significantly higher than those of Group NS on POD 1. The TGF-beta1 levels of Group S were significantly higher than those of Group NS on POD 3 and 5. The TGF-alpha levels were not different at any time points studied. These results indicate that a small-for-size graft retains the capacity to regenerate faster by modulation of expression pattern of HGF and TGF-beta1 immediately after LDLT. After the acceleration of the regenerative response by HGF, subsequent elevation of TGF-beta1 synergistically controls graft size, regulating uncontrolled proliferation of hepatocytes.


Tenascin expression at the invasive front is associated with poor prognosis in intrahepatic cholangiocarcinoma

United States and Canadian Academy of Pathology

Tenascin and decorin are components of the extracellular matrix (ECM) that are implicated in cell proliferation in tumors. Here, we propose that abnormal expression of stromal ECM may play an important role in the progression of intrahepatic cholangiocarcinoma, which is characterized by desmoplastic reaction. To explore this hypothesis, we performed immunohistochemical analysis in order to examine the expression and distribution of tenascin and decorin in 75 cases of intrahepatic cholangiocarcinoma. In the intratumoral stroma, positive staining for tenascin was observed in 51 (68%) cases, and positive staining for decorin was observed in 61 (81%) cases. However, at the invasive front, positive staining for tenascin was found in 23 (31%) cases, and positive staining for decorin was found in 6 (8%) cases. Decorin staining was not correlated with aggressive behavior of intrahepatic cholangiocarcinoma, whereas intratumoral tenascin staining was correlated with lymphatic permeation and proliferative activity measured by Ki67. Tenascin staining at the invasive front was associated with tumor size, lymphatic permeation, lymph node metastasis, and proliferative activity and appeared to be a useful prognostic factor by univariate analysis, although it was not an independent prognostic factor. These results indicate that tenascin plays a role in tumor progression in cases of intrahepatic cholangiocarcinoma and that tenascin expression, especially at the invasive front, may be a useful marker in evaluating an unfavorable prognosis in patients with intrahepatic cholangiocarcinoma.


Antioxidant and anti-inflammatory effects of a diet supplemented with sesamin on hepatic ischemia-reperfusion injury in rats


Analysis of the prognostic factors for liver metastasis of gastric cancer after hepatic resection: a multi-institutional study of the indications for resection


Antisense RNAs transcribed from the upstream region of the precore/core promoter of hepatitis B virus

The bidirectional activity of the precore/core promoter of hepatitis B virus (HBV) has been demonstrated in cultured cell lines. However, HBV antisense transcripts (asRNAs) have not been demonstrated in vivo. In the present study using liver tissue from patients with chronic hepatitis, an anchored 5'RACE mapping the 5' ends at position 1680/1681, 1655 or 1609/1602 was carried out. In limited cases, RLM-3'RACE detected asRNAs to terminate at four or five consecutive dT residues in the 0.7 kb downstream region. PCR of oligo(dT)-primed cDNA did not amplify a typical polyadenylated asRNA. RT-PCR using various primers did not detect any spliced forms. Competitive RT-PCR estimated the copy numbers of the asRNAs to be 0.05-0.4 % of total sense RNAs. All sequenced asRNAs had ORF6 but, in one patient, the asRNA initiating at position 1680/1681 had additional initiation and termination codons in front of ORF6. Therefore, asRNAs are transcribed by RNA polymerase III at a low level, encompass a dispensable ORF6 gene and might be retained in the nucleus. The endogenous asRNAs complementary to the common ends of all sense RNAs suggest antisense-mediated self-regulation of hepadnavirus.


The role of MTA1 gene expression in human hepatocellular carcinoma

The MTA1 gene has been identified as metastasis-associated gene and has been seen to correlate with the degree of invasion and lymphatic metastasis in gastric, colorectal, and esophageal carcinomas. We investigated the possible role of MTA1 gene expression in hepatocellular carcinoma (HCC). The mRNA expression level of the MTA1 gene was examined using reverse transcription polymerase chain reaction (RT-PCR) in HCC and paired non-tumor liver tissues which were obtained from 33 patients who underwent curative hepatectomy. The expression level of each case was calculated as tumor/non-tumor (T/N) ratios. To clarify the clinical significance of MTA1 gene expression in HCC, patient disease-free survival rate after hepatectomy were univariately analyzed using 25 clinicopathological variables, including MTA1 expression level. High expression (T/N > or =1) of the MTA1 gene in HCC as compared to the paired non-tumor tissues was recognized in 14 of 33 (42%) samples. With regard to the differentiation of HCC, the high expression of MTA1 gene in well or moderately differentiated HCC and poorly differentiated HCC were observed in 9 of 27 (33%) and 5 of 6 (83%) samples, respectively. There was no relation between expression levels of the MTA1 gene and cancer invasion to the portal vein or intrahepatic metastasis. However, the disease-free survival rate of the MTA1-high expression group (T/N > or =1) was significantly lower than that of the MTA1-low expression group (T/N <1) (p<0.05). High expression of the MTA1 gene is suggested to be a new prognostic indicator after curative hepatectomy for HCC.


Histone deacetylase inhibitor trichostatin A induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells

Remodeling of the chromatin template by inhibition of HDAC activities represents a potential transcriptional therapy for neoplastic disease. A number of HDAC inhibitors that modulate in vitro cell growth and differentiation have been developed. We analyzed the effects of TSA, a specific and potent HDAC inhibitor, on the human hepatoma cell lines HepG2 and Huh-7. TSA increased levels of acetylated histones H3 and H4 in both HepG2 and Huh-7. It inhibited cell proliferation in vitro and induced G(0)/G(1) arrest in HepG2 and apoptosis in Huh-7. Gene expression of liver-specific functions and liver-enriched transcription factors was upregulated by TSA. TSA upregulated the ammonia removal rate and the albumin synthesis rate of HepG2 and Huh-7. Our results indicate that TSA can induce cell-cycle arrest/apoptosis and hepatocyte differentiation in human liver cancer cell lines.


A robotic surgery system (da Vinci) with image guided function--system architecture and cholecystectomy application


有限要素法による肝臓手術ナビゲーションに関する研究

有限要素法による肝臓手術ナビゲーションに関する研究


Low-dose cisplatin plis oral tegafur and uracil for the treatment of lung metastases of hepatocellular carcinoma


Efficacy of a polyurethane foam/spheroid artificial liver by using human hepatoblastoma cell line (Hep G2)


A.肝 17. 肝細胞眼ー外科手術と集学的治療

A.肝 17. 肝細胞眼ー外科手術と集学的治療


Potent cytotoxic effect of the trans10, cis12 isomer of conjugated linoleic acid on rat hepatoma dRLh-84 cells


Dose-dependent effect of dietary conjugated linoleic acid on the growth of rat hepatoma dRLh-84 cells in vivo

The Japanese Society of Food & Nutrition and the Vitamin Society of Japan

In this study, the effect of varying doses of conjugated linoleic acid (CLA) on the growth of transplanted hepatoma dRLh-84 cells and the relationship between tumor growth and prostaglandin (PG) E2 production or cyclooxygenase (COX)-2 expression were examined. Donryu rats were fed an experimental diet containing 0, 0.1, 0.5, or 2 wt.% CLA for 3 wk, and then dRLh-84 cells were transplanted into the liver. Results show that dietary CLA (0.5 and 2 wt.%) significantly enhanced the growth of the transplanted hepatoma cells compared to the non-CLA diet group at 20 d after cell transplantation. Tumor weight at 10 d after transplantation was also significantly higher in the 2 wt.% CLA group than in non-CLA fed rats. Ten days after transplantation, the PGE2 level in the tumor tissue was shown to be depressed in a CLA dose-dependent manner. Cyclooxygenase-2 (COX-2) mRNA expression in the tumor also tended to be lower in the CLA group than in the non-CLA diet group 10 d after transplantation. Dietary CLA did not affect the tumor phospholipid arachidonic acid level, which is a substrate for PG synthesis. These results indicate that dietary CLA of at least 0.5 wt.% enhances the growth of transplanted dRLh-84 cells in vivo. It is believed that growth promotion of dRLh-84 cells in vivo by CLA cannot be clarified by the PG synthesis dependent mechanism.


The utility of keratin 903 as a new prognostic marker in mass-forming-type intrahepatic cholangiocarcinoma

the United States and Canadian Academy of Pathology,Inc


Video-assisted thoracoscopic extirpation of a posterior mediastinal mass using the da Vinci computer enhanced surgical system

A 28-year-old woman presented a left posterior mediastinal mass surrounded by the intercostal vein, hemiazygos vein, sympathetic nerve, and descending aorta. We successfully resected the mass, that was revealed to be a bronchogenic cyst, by a totally thoracoscopic procedure using the da Vinci computer-enhanced system (Intutive Surgical, Mountain View, CA) without injuring the neighboring structures or the capsule of the mass.


最新消化器内視鏡治療 第2部 第14章 --- 肝臓，胆道，膵臓，脾臓疾患に対する腹腔鏡下手術 7.凝固療法(MCT,RFA)


Morphologic approach to hepatocellular carcinoma development in man: de novo or the so-called 'dysplastic nodule-carcinoma' sequence?

The so-called dysplastic nodule-carcinoma sequence in the liver is generally accepted because hepatocellular carcinoma is not an uncommon finding in precancerous lesions. In order to evaluate the existence and frequency of de novo hepatocarcinogenesis we studied 112 surgically resected early well-differentiated hepatocellular carcinomas showing replacing growth without less differentiated component in themselves. They were divided into two groups: carcinoma in dysplastic area (type A) and carcinoma without dysplastic area (type B) and were analyzed clinicopathologically. We encountered 77 cases of type A (68.8%) and 35 of type B (31.2%). The frequency of type A in cirrhotic group (74.7%) is statistically higher than that of non-cirrhotic group (54.5%) (p=0.0453). Using multivariate analysis, the occurrence of type A was related with higher age, the presence of cirrhosis and hepatitis B surface antigen positive. The tumor size and the presence of fatty change in the tumor tended to relate with type A. We propose two pathways morphologically in early hepatocarcinogenesis, one of which has a close relation to hepatitis B virus and/or cirrhosis.


Optimal multi-phase three-dimensional fast imaging with steady-state free precession dynamic MRI and its clinical application to the diagnosis of hepatocellular carcinoma

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). 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). 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. 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.


Sequential hemodynamic change in hepatocellular carcinoma and dysplastic nodules: CT angiography and pathologic correlation


c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholangiocarcinoma

the British Division of the International Academy of Pathology

The c-erbB-2 and c-Met proto-oncogenes are important for tumour invasiveness and metastasis in many types of malignant tumours. Previous studies have indicated that these proteins are associated with carcinogenesis in intrahepatic cholangiocarcinoma. In this study, we examined c-erbB-2 and c-Met expression by immunohistochemistry in hepatolithiasis, intrahepatic cholangiocarcinoma and metastatic lymph node, in order to clarify whether these proteins play a role in carcinogenesis and tumour metastasis in intrahepatic cholangiocarcinoma. In hepatolithiasis, the staining for c-erbB-2 was positive in 14 of the 23 (61%) cases, while staining for c-Met was positive in eight of the 23 (35%) cases. In intrahepatic cholangiocarcinoma, staining for c-erbB-2 was positive in 45 of the 81 (55%) cases, while staining for c-Met was positive in 28 (35%) cases. The positivity of c-Met staining in intrahepatic cholangiocarcinoma was significantly higher in the differentiated type of cholangiocarcinoma than in the undifferentiated type. In addition, c-Met-positive staining had an inverted correlation with tumour size, the presence of perineural invasion and the presence of lymph node metastasis. c-Met staining had a significantly higher positivity in cases at an early stage of intrahepatic cholangiocarcinoma. In contrast, the positivity of c-erbB-2 staining in intrahepatic cholangiocarcinoma was significantly higher in cases with lymph node metastasis than in cases without. In metastatic lymph nodes, the staining for c-erbB-2 was positive in 20 of the 25 (80%) cases, while staining for c-Met was positive in six of the 25 (24%) cases. There was no difference in survival between c-erbB-2-positive and negative patients. However, the patients with c-Met-positive tumours had a significantly longer survival than those with c-Met-negative tumours in the medium survival term. The multivariate analysis showed the presence of lymph node metastasis, lymphatic permeation and histological differentiation to be independent prognostic factors. These results indicate that increased c-Met expression participates in cholangiocarcinogenesis and in the early developmental stages of intrahepatic cholangiocarcinoma, while increased c-erbB-2 expression contributes to the development of cholangiocarcinogenesis into an advanced stage associated with tumour metastasis.


A comparison of right-lobe and left-lobe graft for living-donor liver transplantation


The Sialyl Lewis X expression in hepatocarcinogenesis: Potential predictor for the emergence of hepatocellular carcinoma


The role of thymidine phosphorylase and thrombospondin-1 in angiogenesis and progression of intrahepatic cholangiocarcinoma


Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment

We describe a preclinical study of our original hybrid artificial liver support system (HALSS) for a clinical trial. We designed a HALSS comprising a multi-capillary polyurethane foam packed-bed module (MC-PUF module) containing a total 200 g (2 x 10(10) cells) porcine hepatocytes, and an extracorporeal circulation device. Almost all porcine hepatocytes in the MC-PUF module formed many spherical multicellular aggregates (spheroids). This extracorporeal circulation device was improved to promote solute exchange between a living body and a MC-PUF module by including a plasma bypass line in the circulation loop. The efficacy of the HALSS was evaluated using a 25-kg pig with warm ischemic liver failure by portocaval shunt and ligation of hepatic artery (HALSS group, n=3). As a control experiment, the same system without hepatocytes in the module was used with the same kind of liver failure pig (Control group, n=3). The blood ammonia in the control group was 143 N-microg/dl at the start of circulation, and rapidly increased to 351 N-microg/dl at 2 hours and to 704 N-microg/dl at 6 hours. But the blood ammonia in the HALSS group was completely suppressed, and remained less than the hepatic coma level (over 200 N-microg/dl) during the circulation time. The blood glucose in the control group gradually decreased, and became less than 40 mg/dl within 6 hours of circulation. But the blood glucose in the HALSS group was maintained well, and remained the normal glucose level (50 - 105 mg/dl) for more than 20 hours of circulation. Improvement in blood creatinine and lactate, and the stabilization of vital signs and urinary excretion, were observed in the HALSS group. The survival time of the pigs in the HALSS group was 19.3 hours compared with 8.9 hours in the control group. In conclusion, our HALSS was effective to stabilize the general conditions of the body in addition to supporting various liver functions. These results suggest that our HALSS has a strong possibility to be used in treating liver failure patients. We have applied for approval of the clinical trial of our HALSS to our institutional ethics committee.


A 16-year experience in performing hepatic resection in 303 patients with hepatocellular carcinoma: 1985-2000


ロボット手術システム(da Vinci)のための術中ナビゲーターの開発

ロボット手術システム(da Vinci)のための術中ナビゲーターの開発


High metabolic function of primary human and porcine hepatocytes in a polyurethane foam/spheroid culture system in plasma from patients with fulminant hepatic failure


Mass preparation of primary porcine hepatocytes and the design of a hybrid artificial liver module using spheroid culture for a clinical trial

To isolate a large number of porcine hepatocytes, we originally developed a mass preparation method that combined the usual collagenase perfusion method of a whole liver with a collagenase redigestion method of tissue fragments after liver perfusion. Using a pig of 10kg, collagenase perfusion only resulted in a yield of 63+/-78 x 10(8) total cells with a viability of 69.2+/-25.3 %, but our combined method had a yield of 167+/-31 x 10(8) total cells with a viability of 87.9+/-4.4% (mean +/- SD). Also, the combined method was applied to two pigs of 10kg body weight at the same time, and isolated 387+/-89 x 10(8) hepatocytes with a viability of 87.1+/-6.9% and a purity of 93.6+/-2.8 % in 11 experiments. We designed a large multi-capillary polyurethane foam (MC-PUF) packed-bed module containing 1 x 10(10) porcine hepatocytes on a clinical trial scale. The porcine hepatocytes in the module formed spherical multicellular aggregates (spheroids) of 200 - 500 microm diameter. Most hepatocytes forming spheroids were viable judged by fluorescein diacetate and ethidium bromide staining. The activities of ammonia removal, albumin secretion and oxygen consumption of the large MC-PUF module were the same as for a small MC-PUF module containing 2 x 10(8) porcine hepatocytes, and were maintained for at least 9 days of culture. These results show that a large MC-PUF module is successfully scaled up 50 times. In conclusion, we succeeded in developing a mass preparation method of porcine hepatocytes and a large hybrid artificial liver module on a clinical trial scale.


Thoracoscopic thymomectomy with the da Vinci computer-enhanced surgical system

The American Association for Thoracic Surgery


Altered expression of beta-catenin without genetic mutation in intrahepatic cholangiocarcinoma

the United States and Canadian Academy of Pathology,Inc


Expression of a tumor-associated antigen RCAS1 in hepatocellular carcinoma

RCAS1 has been reported as a tumor-associated antigen in uterine and ovarian carcinomas. In vitro studies on RCAS1 indicated that it might function as an apoptosis-inducing factor since binding between RCAS1 and its receptor induced apoptosis in receptor-expressing cells. In this study, 68 surgically resected samples of hepatocellular carcinoma (HCC) were prepared and RCAS1 expression was examined immunohistochemically, because RCAS1 was also positive in all HCC cell lines tested. Clinical and pathological parameters were then compared between RCAS1-positive and -negative HCC cases. As a result, RCAS1 is expressed in 26.5% of HCC cases and vascular invasion is observed at a much higher rate in the RCAS1-positive cases (72.2%) than in RCAS1-negative cases (24.0%). RCAS1 is not an antigen specific for gynecological cancers. In HCC cases, the RCAS1-positive percentage is not high, however, RCAS1-positive HCCs exhibited a trend towards invasive character.


Thrombectomy before hepatic resection for hepatocellular carcinoma with a tumor thrombus extending to the inferior vena cava


Liver metastasis from gallbladder carcinoma: anatomic correlation with cholecystic venous drainage demonstrated by helical computed tomography during injection of contrast medium in the cholecystic artery


Clinicopathological characteristics of patients with extrahepatic recurrence following a hepatectomy for hepatocellular carcinoma

None of the previous studies have compared the prognosis or clinicopathological factors between the patients with extrahepatic recurrence and those with intrahepatic recurrence of hepatocellular carcinoma after a hepatic resection. The clinicopathological features and prognoses of patients with extrahepatic recurrence after a curative hepatectomy for hepatocellular carcinoma were investigated. Twenty-three patients with extrahepatic recurrence had more advanced-stage hepatocellular carcinoma at the primary operation compared to 186 patients with intrahepatic recurrence. After adjusting for tumor size, the prognosis of the 2 groups were comparable. However, among the patients with hepatocellular carcinoma exceeding 5 cm in diameter, the number of patients whose plasma levels of des-gamma-carboxy prothrombin was higher than 2.0 AU/mL in the patients with extrahepatic recurrence (62.5%) was significantly more (P < 0.05) than that in the patients with intrahepatic recurrence (20.0%). On the other hand, the prognosis of the 13 patients with extrahepatic recurrence alone was significantly better than in the 10 patients with both intrahepatic and extrahepatic recurrences. The prognoses of the 3 patients who underwent a surgical resection for isolated extrahepatic recurrence were markedly better than that of the remaining 10 patients only treated palliatively. If patients have tumors exceeding 5 cm in diameter and their plasma levels of des-gamma-carboxy prothrombin are higher than 2.0 AU/mL, more careful follow-up examinations than usual may thus be necessary in order to detect extrahepatic recurrence as early as possible. Furthermore, a surgical resection for the isolated extrahepatic recurrence of hepatocellular carcinoma is also recommended to produce long-term survivors.


Characteristics of multicentric hepatocellular carcinomas: comparison with intrahepatic metastasis

Characteristics of multicentric hepatocellular carcinomas (HCCs) remain obscure. We therefore aimed to clarify them and compare them with HCC with intrahepatic metastases. A series of 118 patients who had definite hepatitis C viral status and multinodular HCC were divided into two groups: a multicentric occurrence (MO) group (n = 38), with multicentric HCCs; and an intrahepatic metastasis (IM) group (n = 80), with HCC having intrahepatic metastases. Clinicopathologic variables, including the patient's survival and disease-free survival rates, were compared between the MO and IM groups. Univariate analysis revealed the presence of esophageal varices, the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, hepaplastin test, gamma-globulin, the histologically active hepatitis, tumor size, des-gamma-carboxy prothrombin > 0.1 AU/ml, positive portal vein invasion, and histologic grade as discriminating factors. The MO score to differentiate multicentric HCCs from intrahepatic metastatic HCCs was determined using the following four independent factors selected by a stepwise regression analysis: the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, tumor size, and histologic grade. The sensitivity and specificity of the MO scores using those factors were 84% and 70%, respectively, when the cutoff value was 0.4. The disease-free survival rate in the MO group was similar to that in the IM group, whereas the survival rate in the MO group was significantly better than that in the IM group. The multivariate analysis revealed the multicentric occurrence of HCC as one of the independent prognostic factors. Clinicopathologic factors differentiating multicentric HCCs from intrahepatic metastatic HCCs were the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, small tumor size, and low histologic grade.


Retrospective study on the effects of lipiodolization before a potentially curative hepatectomy for colorectal liver metastases: long-term results of a pilot study


Small graft for living donor liver transplantation

To evaluate the impact of graft size on recipients in living donor liver transplantation (LDLT) to establish a clinical guideline for the minimum requirement. Although the minimum graft size required for LDLT has been reported to be 30% to 40% of graft volume (GV)/standard liver volume (SLV), the safety limit of the graft size was unknown. A total of 33 cases of LDLT, excluding auxiliary transplantation, were reviewed with a minimum observation period of 4 months. The 33 patients were divided into three groups according to GV/SLV: medium-size graft group, small-size graft group, and extra-small graft group. The effect of GV/SLV on graft function, graft regeneration, and survival was evaluated. The overall patient survival rate was 94% at a mean follow-up of 15 months with a minimum observation period of 4 months. There were no statistically significant differences in postoperative bilirubin clearance, alanine aminotransferase, prothrombin time, and frequency of postoperative complications among the three groups. One week after transplantation, the regeneration rate (GV at 1 week/harvested GV) in the extra-small and small groups was significantly higher than that of the medium group. The graft and patient survival rates were both 100% in the extra-small group, 75% and 88% in the small group, and 90% and 95% in the medium group. Small-for-size grafts less than 30% of SLV can be used with careful intraoperative and postoperative management until the grafts regenerate.


Serum leptin levels in patients with nonalcoholic chronic liver disease


Hybrid artificial liver using hepatocyte organoid culture

The International Federation for Artificial Organs

We developed 2 types of hybrid artificial liver modules using hepatocyte organoid culture. One was a polyurethane foam (PUF)/hepatocyte spheroid packed-bed module. Hepatocytes spontaneously formed spheroids in the PUF pores, and they maintained liver-specific functions well for at least 2 weeks in vitro. As a preclinical experiment, a hybrid artificial liver with 200 g porcine hepatocytes was applied to a pig (25 kg) with liver failure and showed that the hybrid artificial liver was effective in support of liver functions and stabilization of general conditions. We established a new technique of hepatocyte organoid formation using centrifugal force. A hepatocyte organoid formed by centrifugation in hollow fibers maintained functions for more than 4 months in vitro. We developed a new sinusoid-like structure module having hollow fibers arranged by spacers in a micro-regular arrangement. Inoculated hepatocytes in the extra-fiber space of the module formed the organoid by centrifugation, and they maintained the functions for at least 1 month in vitro. The results indicated that this module seems to be promising as a hybrid artificial liver.


Correlation of three-dimensional gradient echo dynamic MR imaging with CT during hepatic arteriography in patients with hypervascular hepatocellular carcinomas: preliminary clinical experience

International Society for Magnetic Resonance in Medicine

The purpose of this study is to elucidate the usefulness of dynamic MR study of the whole liver using 3DFISP with double dose gadolinium (Gd) enhancement in detecting enhancing lesions in 20 patients. Twenty patients with hepatocellular carcinoma (HCC) underwent 3DFISP dynamic study with double dose Gd. The demonstration of enhancing hypervascular lesions regardless of etiology was evaluated on a segment-by-segment basis with receiver operating characteristic (ROC) analysis, using findings on CT during hepatic arteriography as a gold standard. Diagnostic accuracy of 3DFISP in the detection of HCC was also evaluated. As to the demonstration of enhancing lesions, the Az value of the ROC curve was 88%. The detection rate of HCC with 3DFISP was 98%. 57% of enhancing pseudolesions were not detected on 3DFISP. We concluded that Dynamic MR study of the whole liver using 3DFISP with double dose Gd enhancement is a useful method to demonstrate hypervascular HCC.


Efficacy of three-dimensional fast imaging with steady precession dynamic MR imaging in evaluating pancreatic ductal adenocarcinoma

To compare the diagnostic efficacy of three-dimensional fast imaging with steady precession (3D-FISP) dynamic MR imaging in assessing pancreatic ductal adenocarcinoma with conventional MR imaging and helical CT, 15 patients with surgically proven pancreatic ductal adenocarcinoma were studied. Contrast-to-noise ratio (CNR) of the tumor, tumor detectability, local tumor extension, and vascular involvement were evaluated for all techniques. The results indicate that 3D-FISP dynamic MR imaging may improve the imaging assessment of pancreatic ductal adenocarcinoma.


Effect of dietary conjugated linoleic acid on the in vivo growth of rat hepatoma dRLh-84

We examined the effect of dietary conjugated linoleic acid (CLA) on the growth of injected hepatoma dRLh-84 in Donryu rats. After experimental diets containing 0% or 2% CLA were given to male Donryu rats for 3 wk, dRLh-84 cells were injected into the left lobe of the hepatic capsule, and the experimental diet was continued. The cells formed a solid tumor > or = 1 wk after the injection, and thereafter the tumor grew with feeding duration. In a morphological study, this tumor appeared to be a low-differentiated hepatoma, and there was no remarkable difference in the morphology of the tumor between 0% and 2% CLA groups. Tumor weight was significantly higher in the 2% CLA group than in the 0% CLA group throughout the feeding period after the injection. Serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities were significantly higher in 2% CLA-injected rats than in 0% CLA-injected rats at 3 wk after the injection. CLA upregulated acyl-CoA oxidase activity, especially 1 wk after the injection. However, dietary CLA did not activate carnitine palmitoyl transferase II, which is a rate-limiting enzyme in the mitochondrial beta-oxidation pathway. Natural killer cell activity in the spleen tended to be higher in injected rats, but a significant effect of dietary CLA was not recognized. Serum interferon-gamma and tumor necrosis factor-alpha levels were higher in injected than in sham rats. Moreover, these levels were higher in 2% CLA groups than in the respective 0% CLA groups.


ナビゲーション機能を備えたロボット手術システム(da Vinci)の開発

ナビゲーション機能を備えたロボット手術システム(da Vinci)の開発


肝細胞癌切除例に対するUFTの再発予防効果の検討

肝細胞癌切除例に対するUFTの再発予防効果の検討


Development of a Hybrid Artificial Liver Support System and Preclinical Animal Experiments


Expression and antitumor effects of TRAIL in human cholangiocarcinoma

American Association for the Study of Liver Diseases


Conditions required for a hybrid artificial liver support system using a PUF/hepatocyte-spheroid packed-bed module and it's use in dogs with liver failure

We studied the effects of a hybrid artificial liver support system we developed on dogs with hepatic failure. The system consisted of a multi-channel polyurethane foam packed-bed culture module, including primary dog hepatocyte spheroids. Blood ammonia was well metabolized by 20 g hepatocytes, but the other functions such as glucose concentration, total bile acid concentration, and survival time required 30 g hepatocytes to improve conditions. We found that we should use a culture substratum that easily forms spheroids, and that an artificial liver module should be used as soon as possible after spheroid formation by hepatocytes in the module.


Small hepatocellular carcinoma with minute satellite nodules


Surgical indications for advanced hepatocellular carcinoma


Characteristics of sarcomatous cholangiocarcinoma of the liver

The aim of this study was to clarify the clinicopathological characteristics of intrahepatic cholangiocarcinoma with sarcomatous changes. Four cases of cholangiocarcinoma with sarcomatous change were identified and investigated. The clinicopathological findings, including the results of immunohistochemical staining, were investigated in comparison with those of ordinary cholangiocarcinoma. Two of them exhibited pyrexia as the initial symptom. The serum alkaline phosphatase level in sarcomatous cholangiocarcinoma was significantly lower than that in ordinary cholangiocarcinoma. Both the serum carcinoembryonic antigen and carbohydrate 19-9 level in sarcomatous cholangiocarcinoma also tended to be lower than those in ordinary cholangiocarcinoma. The carcinomatous component of all tumors was mostly poorly differentiated adenocarcinoma. The associated microscopic findings were as follows: lymphocyte infiltration in the tumor, accompanied by both necrosis and extensive lymph node metastases. Three of them predominantly exhibited spindle-shaped sarcomatous changes, whereas the other case predominantly demonstrated pleomorphic-type sarcomatous changes. The sarcomatous area was positive for both vimentin, a mesenchymal marker, and for epithelial markers, furthermore, in 3 of 4 cases, the carcinoma portions were also positive for vimentin. The overall survival curves were not significantly different between the 2 groups, however, no long-term survivor was found in sarcomatous cholangiocarcinoma. The main characteristics of cholangiocarcinoma with sarcomatous changes are considered to be as follows: 1) often demonstrating pyrexia as a symptom; 2) not always demonstrating remarkable abnormal findings in the laboratory data including tumor markers; 3) histologically showing poorly differentiated adenocarcinoma; and 4) showing a very poor prognosis (especially, in a pleomorphic-type).


Recent developments in imaging diagnostics for HCC: CT arteriography and CT arterioportography evaluation of vascular changes in premalignant and malignant hepatic nodules


Development of a hybrid artificial liver using a polyurethane foam/hepatocyte-spheroid packed-bed module

Primary dog hepatocytes spontaneously formed spheroids in the pores of polyurethane foam (PUF) within 1-2 days of stationary culture. The spheroids, about 100-150 microm in diameter, partly attached to the surface and immobilized inside these pores. The lidocaine disappearance rate decreased to about 4 microg/10(5) viable cells/day for 10 days, while in the PUF/spheroid culture the rate was maintained at almost the initial level of 8 microg/10(5) viable cells/day for 10 days. Then, two scales of PUF packed-bed modules were designed. A small module (PUF volume; 14.5 cm3) was used for in vitro culture to investigate optimum culture conditions, and a large module (PUF volume; 300 cm3) was designed for dog experiments. Hepatocytes inoculated in these modules also formed spheroids and maintained almost the same activity of albumin secretion rate (111 microg/cm3 PUF/day in the small module and 87.7 microg/cm3 PUF/day in the large module). These results indicate that the PUF packed-bed module containing hepatocyte-spheroids is promising as a hybrid artificial liver.


MR cholangiopancreatographic differentiation of benign and malignant intraductal mucin-producing tumors of the pancreas


Clinicopathological characteristics of surgically resected minute hepatocellular carcinomas


肝臓手術ナビゲーションシステム開発を目的とした術中肝臓変形に関する基礎的検討

肝臓手術ナビゲーションシステム開発を目的とした術中肝臓変形に関する基礎的検討


肝切除における三次元エコーによる術中ナビゲーション

肝切除における三次元エコーによる術中ナビゲーション


Impact of combined preoperative three-dimensional computed tomography and intraoperative real-time three dimensional ultrasonography on liver surgery


Vascular changes in hepatocellular carcinoma: correlation of radiologic and pathologic findings


Radiologic features of intrahepatic bile duct adenoma: a look at the surface of the liver

We report the radiological features of intrahepatic bile duct adenoma (BDA) in three patients. BDA was shown as a small mass located in the peripheral region of the liver with each imaging modality: a hypervascular mass on angiography and a mass appearing as early nodular enhancement found disproportionately evident compared with their small size and distinct delayed or prolonged enhancement on CT. BDA should be included in the diseases to be differentiated from hypervascular hepatic tumors.


Formation of porcine hepatocyte spheriacal multicellular aggregates (spheroid) and analysis of drug metabolic functions


Risk factors of the recurrence of hepatocellular carcinoma originating from residual cancer cells after hepatectomy

Little has been documented to differentiate between recurrence originating from microscopic residual tumor cells and recurrence due to metachronous multicentric origin of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence closely related to residual tumor cells. A retrospective review of hepatic resections for HCC during the period between April 1985 and April 1997 was undertaken at a University Hospital with a long history of hepatectomy for HCC. Three hundred and thirteen HCC patients without any definite multicentric recurrence, who underwent hepatectomy, were retrospectively investigated. Main outcome measures were: (Study 1) Risk factors for recurrence were univariately and multivariately investigated among various clinicopathological variables, including the vi factor as a new indicator of the potential malignancy of HCC (i.e., the presence of both microscopic portal vein invasion and intrahepatic metastasis). (Study 2). The risk factors for recurrence were then analyzed according to the period of recurrence. (Study 1) Independent risk factors were: (tumor factors) a positive vi factor, alpha-fetoprotein > 100 ng/ml, and poorly differentiated histology; (host factors) albumin < 3.8 g/dl, the presence of diabetes mellitus, platelet count < 14 x 10(4)/microliter, Y-globulin fraction > 20%. In those risk factors, the relative risk of the vi factor (2.6) was the largest. (Study 2) Within 1 year after hepatectomy, only tumor factors, including the vi factor and poorly differentiated histology, were significant risk factors, tumor factors were significant only up to 2 years after hepatectomy, and thereafter only host factors were significant. The risk factors for non-multicentric recurrence of HCC are considered to be a positive vi factor, alpha-fetoprotein, and poorly differentiated histology, and the vi factor is considered to be a new prognostic indicator expressing the potential malignancy of HCC such as invasion and metastasis.


The effect of octreotide on morphological hepatic regeneration and hepatic functional recovery after a two-thirds hepatectomy in rats

The aim of this study was to clarify the effect of octreotide on either morphological hepatic regeneration or hepatic function after a two-thirds hepatectomy in rats. The rats were separated into two groups as follows: group 1 received 100 microg of octreotide acetate subcutaneously every 6 hours from 24 hours before hepatic resection until sacrifice; group 2 received 0.9% saline solution instead of octreotide as a control. Morphological hepatic regeneration, protein synthesis and mitochondrial function were all studied. The regenerative rate in liver volume and the BrdU labeling index in group 1 were significantly lower than those in group 2. The levels of glutamic acid dehydrogenase were significantly lower in group 1 than those in group 2 at 24 (64.2+/-14.6 and 77.8+/-8.3 IU/l, respectively), 36 (46.1+/-14.4 and 60.6+/-5.9 IU/l, respectively) and 48 hours (39.7+/-13.7 and 51.0+/-11.8 IU/l, respectively) after hepatectomy. At 24 hours after hepatectomy, the levels of arterial ketone body ratio was higher in group 1 than in group 2 (0.67+/-0.05 and 0.51+/-0.07, respectively), and the energy charge of the liver was also higher in group 1 than in group 2 (0.662+/-0.031 and 0.605+/-0.053, respectively). Our results suggest that morphological hepatic regeneration is not necessarily synchronized with hepatic functional recovery. In addition, hepatic functional recovery was preserved by keeping the energy metabolism in hepatocytes, even when the use of octreotide suppressed morphological hepatic regeneration.


The mechanism of hepatic graft protection against reperfusion injury by prostaglandin E1


Cell proliferation and cell loss in nodule-in-nodule hepatocellular carcinoma

In order to clarify the significance of the balance between cell proliferation and cell loss during the progression of hepatocellular carcinoma, 16 operative specimens of nodule-in-nodule hepatocellular carcinoma were investigated. In 16 specimens, cell proliferation was evaluated by the expression of Ki-67 nuclear antigen, and cell loss was also examined by the method of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The expressions of p53 protein, bcl-2 protein and Fas antigen were also investigated to clarify the relationship between their expression and cell kinetics. The Ki-67 labeling index of the inner nodules was higher than that for the outer nodules (18.9% vs. 7.2%; p < 0.05) and the TUNEL labeling index of the inner nodules was also higher than that for the outer nodules (12.8% vs. 6.6%; p < 0.05). The increasing rate of the Ki-67 labeling index from Edmondson's grade I to II was 3.9 +/- 3.0, that from grade II to III was 3.9 +/- 2.4, while the increasing rate of the TUNEL labeling index from grade I to II was 2.7 +/- 0.3 and that from grade II to III was 1.7 +/- 0.2 (p < 0.05). p53 Protein was observed in 5 cases, while bcl-2 protein was found in 4 cases in the border area of the inner nodule. However, Fas antigen was found in none of the examined cases. Regarding the Ki-67 positive rate in the inner nodule, the Ki-67 positive rate in the p53 protein positive cases was significantly higher than that in the negative cases (30.3 +/- 15.4 vs. 11.9 +/- 9.2; p < 0.05). However, the TUNEL labeling index was not affected by the expression of those proteins. This study suggested that tumor progression depends on a disturbance in the cell kinetic balance caused not by a decrease in the absolute amount of cell loss but in the chaotic balance between cell loss and cell proliferation.


Evaluation of major hepatic resection for small hepatocellular carcinoma

The aim of this study is to clarify the significance of a major hepatectomy for small hepatocellular carcinomas (HCCs). Seventy-eight patients with solitary HCC measuring less than 3 cm in diameter, whose liver function was considered sufficient to tolerate a right hepatic lobectomy, were classified into 2 groups consisting of: a major group (n = 18), who underwent a major hepatectomy (2 segments or more); and, a minor group (n = 60), who underwent a hepatectomy including one segment or less. The early post-operative outcome and the long-term outcomes, comprising patient survival as well as disease-free survival, were compared. In addition, the post-operative long-term changes in liver function tests and esophageal variceal occurrence were also compared. In the post-operative mortality and morbidity, no significant differences were found between the 2 groups. However, 1 patient in the major group unexpectedly died of liver failure 6 months after operation. No significant difference was observed in patient survival and disease-free survival. The platelet count in the major group tended to decline more rapidly than that in the minor group. Furthermore, 1 patient in the major group demonstrated risky esophageal varices 29 months after operation, which had to be treated by endoscopic injection sclerotherapy. Based on the above findings, a major hepatectomy is therefore not recommended for patients with solitary small HCC measuring 3 cm or less in diameter.


Development of a Hybrid Artificial Liver Support System with Porcine Hepatocyte Spheroids for Preclinical Use


Development of a hybrid artificial liver support system and its application to hepatic failure animals


The formation of a spheroid of primary hepatocytes and the expression of liver-specific functions depend on the characteristics of polyurethane foam


A branched chain amino acid-enriched solution does not induce any beneficial effect on the postoperative intestinal functions.


Significance of the peroral phenolsulfonphthalein test in hepatic resection: a possible predictor of bacterial translocation

The aim of this study was to evaluate the perioperative changes in intestinal permeability by using the phenolsulfonphthalein (PSP) test and to also to clarify the significance of the peroral PSP test in hepatic resection. Fifty patients, all of whom underwent hepatic resection, were prospectively studied. Postoperative complications occurred in 16 patients, and 10 of these complications were infectious. A peroral PSP test, which was scheduled before operation and on postoperative days 3, 7, and 14, was performed as follows: after the administration of 30 mg of PSP, a 24-hour urine was collected, and the urinary PSP was measured by colorimetric assay. The correlation between the preoperative PSP value and various clinical variables, such as perioperative changes in urinary PSP excretion, and the relationship between the postoperative PSP value and postoperative complications, were investigated. Preoperative urinary PSP excretion was found to increase in proportion to the degree of liver dysfunction. In contrast, urinary PSP excretion did not significantly change during the perioperative period. However, urinary PSP excretion on postoperative day 3 in patients with postoperative infectious complications (27.3%) was significantly greater than that in those without infectious complications (17.4%; p < 0.05). Furthermore, PSP excretion on postoperative day 3 in those with infectious complications was also significantly greater as compared to the preoperative level. The patients with a urinary PSP excretion level on postoperative day 3 of greater than 25%, exhibited infectious complications more frequently than patients with a level under 25% (60% versus 10.3%, respectively; p < 0.05). The peroral PSP test is thus suggested to be a possible predictor of bacterial translocation after hepatic resection.


Gastroenterological surgery for patients with chronic respiratory insufficiency


A thoracoabdominal hepatectomy and a transdiaphragmatic hepatectomy for patients with cirrhosis and hepatocellular carcinoma


The role of growth hormone, somatostatin and glucagon in hepatic resection

The aim of this study was to clarify the roles of growth hormone, somatostatin, and glucagon in vital reactions against surgical stress as well as in hepatic regeneration. Eleven consecutive patients, who underwent hepatic resection, were included in this study. Changes in intrinsic hormones, specifically growth hormone, somatostatin, and glucagon, were investigated. Furthermore, a comparison was made between major (more than 2 segments) and minor (less than 1 segment) hepatectomies. Growth hormone was observed to increase four-fold during hepatectomy and thereafter remained at relatively high levels. Somatostatin reached its lowest level on postoperative day 1 and then returned to near the preoperative level on postoperative day 7, while glucagon gradually increased and reached a peak around postoperative day 3. The concentrations of both somatostatin and glucagon in the portal vein were higher than those in the peripheral vein. No significant differences between major and minor hepatectomies were found throughout the perioperative course. Growth hormone is considered to be a sensitive parameter in terms of surgical stress and can also act as a trigger as well as a promoter of hepatic regeneration, while a dissociation between somatostatin and glucagon in the early postoperative period indicates the promotion of hepatic regeneration. Furthermore, portal blood, which contains higher concentrations of these substances, plays an important role in regulating hepatic regeneration. However, the absence of a correlation between the extent of the hepatectomy and these parameters suggests that some other, as yet unidentified mechanism, may also be related to the regulation of hepatic regeneration.


初代ブタ肝細胞のポリウレタンフォーム(PUF)/スフェロイド培養法を用いたハイブリッド型人工肝臓開発のための培養条件の検討


Adenosquamous carcinoma of the liver: clinicopathologic characteristics and cytokeratin profile


Urinary excretion of prostaglandins and renal function after hepatic resection


Circulating intercellular adhesion molecule-1 in patients with hepatocellular carcinoma before and after hepatic resection


Significance of alpha-fetoprotein levels for detection of early recurrence of hepatocellular carcinoma after hepatic resection


A comparison of parenteral hyperalimentation and early enteral feeding regarding systemic immunity after major hepatic resection--the results of a randomized prospective study

To compare the nutritional efficacy, especially regarding the systemic immunity of early enteral (EEN) and total parenteral nutrition (TPN) in major hepatic resection. A randomized, prospective controlled study was performed in the Second Department of Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan. Twenty-six patients who underwent a major hepatic resection were divided into 2 groups: EEN (n = 13), and TPN (n = 13). There was no significant difference between the two groups in regard to either clinical backgrounds, nutritional parameters. There was no significant difference in the nutritional parameters after hepatectomy, such as the serum levels of retinol binding protein, transierrin, pre-albumin, and 3-methylhistidine between the two groups. Among the immunologic parameters, NK activity and changes in the lymphocyte number, the PHA response and the NK activity, which was expressed as a percentage of the preoperative values, was significantly higher in the EEN group than in the TPN group (p < 0.05). The incidence of infectious complications in the TPN group was 4 of 13 patients (31%), although the same incidence in the EEN group was only 1 of 13 (8%). In one case of TPN, a bacterial strain of gut origin was isolated from the intra-abdominal abscess, which suggested that bacterial translocation occurred. No significant difference was observed in the nutritional parameters between the EEN and TPN groups. Early enteral feeding maintained immunocompetence, and thus such feeding possibly reduced the rate of infectious complications after major hepatic resection.


PUF/肝細胞スフェロイド充填層型人工肝臓のイヌ温虚血肝不全モデルへの適用

PUF/肝細胞スフェロイド充填層型人工肝臓のイヌ温虚血肝不全モデルへの適用


Hepatic resection for interic type hepatocellular carcinoma


Cardiac complications after hepatic resection


Evaluation of indications for the surgical treatment of cavernous hemangioma of the liver


The role of prostanoid in hepatic damage during hepatectomy

The aim of this study in hepatectomy is to investigate whether or not hepatic ischemia elevates the serum prostanoid levels, and whether or not thromboxane A2 (TXA2) synthetase inhibitor (OKY 046) improves hepatic damage. The prostanoid levels were measured in 22 hepatectomy cases. The beneficial effects of thromboxane A2 synthetase inhibitor were examined in cases who underwent hepatectomy under hemihepatic vascular control. The total prostanoid levels (6-keto PG Fla+ PGE2 + TXB2) were measured in 22 cases before and after hepatectomy. The hepatic ischemic time (HIT) was defined as the time required to perform a hepatic mobilization plus the right hemihepatic vascular control technique. The total prostanoid levels increased after hepatectomy (P < 0.01). The changes in the total prostanoid levels positively correlated with the HIT (P < 0.01). The 17 cases who underwent hepatectomy with the HIT were randomly divided into 2 groups; the OKY group (n = 9), OKY 046 (0.2 mg/kg/hr), the control group (n = 8); no drug was given. The OKY 046 administration reduced the TXB2 levels (P < 0.01), without any changes in the PGE2, or 6-keto PGF1a levels. The serum glutamic oxaloacetic transaminase levels after operation were lower, and the hepaplastin tests were higher in the OKY group than those of the control (P < 0.05). These results demonstrated that hepatectomy under ischemia elevated the prostanoid levels. OKY 046 significantly reduced the TXB2 levels and the degree of hepatic damage in hepatectomy under ischemia.


Nutritional support after hepatic resection: a randomized prospective study

A consensus as to whether hypertonic dextrose should be given to patients with chronic liver diseases such as cirrhosis or chronic hepatitis after major hepatectomy has not been reached, mostly because metabolism in the remnant liver switches from utilization of blood glucose to utilization predominantly of fatty acid as an energy source. We investigated whether nutritional support would have beneficial effects for such patients. Among 19 patients, 10 were given peripheral dextrose (10 kcal/kg/day) for seven days following hepatectomy and the other 9 were given hypertonic glucose. Twenty and 30 kcal/kg/day was the average non-protein caloric intake, including free oral intake during the first one week following hepatectomy, respectively. The groups were comparable with regard to laboratory data and operative stress. There were no untoward effects related to this support. In patients given nutritional support, retinol binding protein and prealbumin improved (p < 0.05 and p < 0.05, respectively), urinary 3-methylhistidine excretion decreased (p < 0.01) and the nitrogen balance normalized earlier (p < 0.05), as compared to findings with the conventional method. The remnant liver can utilize dextrose and nutritional support improves the nutritional status and may even preserve muscle protein mass.


Renal function after elective hepatic resection

Although morbidity and mortality associated with liver surgery has declined, in particular operative death from liver failure, accumulation of fluid in the peritoneal or pleural cavities after hepatic resection is still the most common post-operative complication and it often decreases the patient's quality of life. The purpose of this retrospective review is to discuss the effect of renal dysfunction following hepatic resection on ascites formation in patients who underwent hepatic resection. The patients who underwent hepatectomy were assigned to two groups; Group A patients (n = 119) had some form of ascites or pleural effusion, either intractable or easily controlled, while Group B patients (n = 178) had neither ascites nor pleural effusion. We compared the clinical and laboratory data, operative risk factors, and the post-operative renal as well as hepatic functions of the two groups. In addition to ordinary risk factors associated with ascites formation such as decreased plasma oncotic pressure due to hypoalbuminemia along with increased hydrostatic pressure in the portal circulation, renal dysfunction after hepatic resection might be the primary cause of fluid accumulation in the peritoneal cavity. As one of the mechanisms of ascites formation following hepatic resection, we must consider the presence of renal dysfunction and protect against ascites formation and treat refractory ascites after hepatic resection not only by such traditional methods such as water and salt restriction, the use of diuretics, and the infusion of albumin products, but also by preserving the renal function after hepatectomy.


Thromboxane A2 in preservation-reperfusion injury: the effect of thromboxane A2 synthetase inhibitor


Retrograde right hepatic trisegmentectomy


組織学的分化度よりみた小肝細胞癌切除の意義

組織学的分化度よりみた小肝細胞癌切除の意義


Chemosensitivity in primary liver cancers: evaluation of the correlation between chemosensitivity and clinicopathological factors


Significance of hyaluronic acid for evaluation of hepatic endothelial cell damage after cold preservation/reperfusion


Prognosis of well differentiated small hepatocellular carcinoma--is well differentiated hepatocellular carcinoma clinically early cancer?

The purpose of this study is to examine whether or not well differentiated (w-d) hepatocellular carcinoma (HCC) is indeed clinically early cancer. Seventy six patients with solitary small HCCs up to 3 cm in diameter, who underwent hepatectomy, were observed for at least 2 years for possible recurrence. These patients were divided into two groups: 10 patients with w-d HCCs (Edmondson and Steiner's grade I) and 66 patients with less differentiated (l-d) HCCs (Edmondson and Steiner's grade I-II, II-III, and III). The histological analysis revealed that w-d HCCs had lower incidences of fibrous capsule formation (P<0.01), when compared to l-d HCCs. There were no significant differences in the incidence of intrahepatic metastasis, or portal vein invasion. In a resected specimen of w-d HCC, barium sulfate and gelatin were injected into portal vein and a transparent specimen was made. The transparent specimen showed that the portal vein in the tumor seemed to be intact. Microscopically, cancer cell infiltration into the fibrous frame of the portal tract was present. There were no significant differences in the disease free survival between the two groups. An analysis of tumor volume doubling time in recurrent foci suggested that minute cancerous foci had been present at the time of operation. W-d HCCs were clinically demonstrated not to be early cancer, because there was no significant difference in disease free survival between the patients with w-d and l-d HCCs.


Early recurrence after surgery of hepatocellular carcinoma

In 231 patients with hepatocellular carcinoma who underwent liver resection from 1986 to 1992 to determine the significance of alpha-fetoprotein (AFP) levels. There were 13 patients (5.6 per cent) with early recurrence within six months after hepatectomy. Preoperative serum alpha-fetoprotein (AFP) levels were significantly higher in patients with early recurrence (p < 0.01). Postoperative histological examination revealed that there were significant correlations between patients with early recurrence and intrahepatic metastasis (p < 0.01), and portal vein infiltration (p < 0.01). There were significant correlations between patients with early recurrence and preoperative diagnosis of intrahepatic metastasis (p < 0.01), however, preoperative diagnosis of portal vein infiltration could not be detected enough. Eight (73%) of 11 patients with over 1000 ng/ml of AFP and preoperative diagnosis of intrahepatic metastasis had early recurrence (p < 0.01). We found that patients of hepatocellular carcinoma with over 1000 ng/ml of AFP and preoperative diagnosis of intrahepatic metastasis are the most important factors in the preoperative clinical data linked to early recurrence type of HCC after hepatectomy.


A refined method of trans-thoracoabdominal hepatectomy for cirrhotic patients with hepatocellular carcinoma

A hepatectomy in cirrhotic patients with hepatocellular carcinoma, located in either the posterior or superior part of the right lobe, inevitably requires a forced mobilization of the right lobe. Such a forced procedure causes a decreased hepatic blood flow resulting in postoperative morbidity and mortality, as well as an increased risk of the intrahepatic dissemination of cancer cells during the operation. We have thus refined the method of trans-thoracoabdominal hepatectomy to minimize those demerits of conventional transabdominal hepatectomies. The main characteristics of our refinements are as follows; (1) an optimal incision for the best short-cut to the hepatocellular carcinoma is determined by a three-dimensional imaging of either helical computed tomography and/or magnetic resonance imaging before operation; (2) a complete view of the operative field is obtained by the pertinent use of rotating the operation table, on which the patient is placed in a left semi-lateral position; (3) this method is suitable for resecting a tumor located in the posterior segment such as a posterior segmentectomy. This refined method is considered to decrease the postoperative morbidity including post-operative hepatic dysfunction and is also useful for cirrhotic patients with hepatocellular carcinoma.


Occurrence of intraperitoneal septic complications after hepatic resections between 1985 and 1990


消化器外科手術後のmethicillin -resistant Staphylococcus aureus 腸炎予防における周術期バンコマイシン投与の意義


Argyrophilic nuclear organizer regions (AgNOR) of resected intrahepatic cholangio cellular carcinoma


The role of interleukin-6, interleukin-1β, tumor necrosis factor-α, and endotoxin in hepatic resection


Oral administration of vancomycin in preventing postoperative methicillin-resistant staphylococcus aureus enterocolitis


肝切除時のプロスタノイド動態に対する Thromboxane A2 synthetase inhibitor(OKY-046) の効果


Detection of hepatitis C virus RNA in the ultrasonic dissector irrigating solution used in liver surgery


Initiation of a fibrinolytic system in hepatic resection: the roles of tissue-type plasminogen activator and plasminogen activator inhibitor-1


Serum hyaluronic acid for the assessment of graft viability in porcine liver transplantation


A comprehensive multi-institutional study of empiric therapy with flomoxef in surgical infections of the digestive organs. The Kyushu Research Group for Surgical Infection

The effect of flomoxef as empiric therapy for surgical infections of the digestive organs was analyzed in 103 patients, most of whom (94.2%) had intra-abdominal infections. Surgical procedures were performed on 73 patients contemporaneously with the flomoxef therapy. Flomoxef is an oxacephem and has a potent and broad bactericidal spectrum against aerobes and anaerobes. It provokes fewer adverse reactions than latamoxef such as vitamin K deficiency and platelet dysfunction. Flomoxef was administered intravenously at a dose 1-4g/day for more than 3 days without any other antimicrobial agent. The clinical response was classified into 3 groups; cured, improved and failed, and both the cured and improved responses were defined as satisfactory. A satisfactory response was obtained in 99 patients (96.1%). Regarding bacteriological response, the overall eradication rate was 81.3%. Adverse reactions including abnormal laboratory data occurred in only two patients. One had abdominal pain, and the other had a mild elevation of transaminases, and both were mild and easily reversible. Therefore, flomoxef is considered to have the potential of becoming one of the most effective agents in empiric therapy for surgical infections of the digestive organs.


Major hepatic resection in patients with a prosthetic heart valve receiving anticoagulation treatment

We experienced two patients with a prosthetic heart valve, who underwent hepatic resection for hepatoma while on anticoagulation therapy. Patients with a prosthetic heart valve have the following characteristics; an increased risk of thromboembolism due to diminished anticoagulation in the perioperative period, a greater risk of endocarditis due to the artificial material in the heart, and impaired cardiopulmonary function including possible arrhythmia and heart failure. Furthermore, when such patients also have liver cirrhosis with a hepatoma, there is an increased risk of perioperative bleeding while on anticoagulation due to coagulopathy and also a risk of infection due to decreased cellular immunity. Patients with a prosthetic heart valve therefore require special care and attention whenever they have to undergo hepatic resection. With respect to anticoagulation, a minimal level is required to prevent bleeding and thromboembolism. Warfarin being administered preoperatively may be switched to heparin while closely monitoring the activated clotting time (biomaterial valve: 130-150 sec, non-biomaterial valve: 150-180 sec); the heparin should then be changed back to warfarin immediately after starting oral intake following operation. For the prevention of infection, a broad spectrum antibiotic should be used prophylactically both intra-operatively and postoperatively. The cardiopulmonary function must also be carefully monitored. For the assessment of postoperative liver function, lecithin: cholesterol acyltransferase, serum bilirubin and albumin are useful because there is no relevance of coagulation parameters such as prothrombin time under anticoagulation.


Indications for major hepatectomy in cirrhotic liver

In an investigation of the indications for major hepatic resection of the cirrhotic liver, the records of 152 consecutive patients who had undergone a right hepatic resection between April 1985 and January 1991 were reviewed. A comparison of right hepatic lobectomy and right partial hepatectomy of the liver with no cirrhotic changes, revealed that postoperative values of serum glutamic pyruvic transaminase were significantly higher after right partial hepatectomy than after right lobectomy, despite the fact that there were no significant differences with respect to preoperative laboratory data, and there was a greater blood loss and total weight of the resected liver in patients receiving a right lobectomy as compared with those undergoing partial hepatectomy. These results suggest that in order to enable a more favorable recovery from hepatic resection, it is essential to avoid both mechanical damage and ischemic injury to the residual liver during hepatic surgery. A total of 77 patients underwent a partial hepatectomy of a cirrhotic liver, and among these patients, 16 patients had values of the indocyanine green test of less than 20%, as well as a portal pressure of less than 200 mm saline. Compared with these 16 cirrhotic patients and those patients who underwent right lobectomy, there were no significant differences with regard to the pre-operative laboratory data and portal pressure. These results therefore suggest that major hepatic lobectomy could be performed on selected patients with cirrhotic livers.


Estimation of degree of liver cirrhosis using a fibrosis score; a multivariate analysis of clinical parameters and resected specimens

We designed this study to estimate the degree of liver cirrhosis using clinical parameters and surgically resected specimens. One hundred and twenty-nine cases who underwent hepatic resection in the Department of Surgery II, Kyushu University Hospital during the period between April 1985 and July 1991 for whom data for all 29 variables evaluated were available, were admitted to this study. On the basis of the histological findings of fibrosis of the liver, the non-neoplastic part of the resected specimens were classified into 3 groups; Z0, no cirrhosis (n = 63), Z1, mild cirrhosis (n = 38), and Z2, severe cirrhosis (n = 28). A univariate analysis revealed 14 significant variables. After multiple logistic regression analysis of these, five independent variables (low platelet count, female, low value of hepaplastin test, a high Pugh's score and a high value of ICG) were identified. We obtained a fibrosis score using the coefficient of each above-mentioned variable. This score increased the discriminative power. The fibrosis score is therefore considered useful for estimating the severity of liver cirrhosis.