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Biomedical subjects

Akio Saiura

Publications and source records attributed to Akio Saiura.

At least 19 recordsLinked to original sources
PubMed2006

Surgical resection of pulmonary metastases from colorectal cancer: Four favourable prognostic factors.

BACKGROUND: Surgical resection has been the first choice for treatment of pulmonary metastases from colorectal cancer; however, indications for surgery have yet to be adequately clarified. In considering strategies for the treatment of pulmonary metastases from colorectal carcinoma, determination of disease status as either systemic or pre-systemic is of primary importance. The aim of this study is to define the characteristics of those patients who are most likely to benefit from surgical resection. METHODS: Fifty-eight patients who underwent pulmonary resection for colorectal metastases were retrospectively reviewed and examined for clinicopathological factors. RESULTS: Overall, 5-year survival rates were 29%, with a median survival time (MST) of 27 months. Multivariate analysis identified four factors that indicate independent and favourable prognostic impact: three or less tumours, metachronous metastasis, negative hilar and/or mediastinal lymph node metastasis and normal prethoracotomy serum carcinoembryonic antigen level. The 5-year survival rate for 16 patients who satisfied all of these favourable characteristics was 62% (MST = 86 months), which was significantly better than those patients lacking these characteristics. The 5-year survival rate for 13 patients who underwent repeated metastasectomy was 37% (MST = 32 months). CONCLUSIONS: The four factors selected in our multivariate analysis appear to be favourable factors for the practical identification of those patients who are most likely to benefit from surgical resection. Repeated pulmonary resection for lung-only recurrence may benefit carefully selected patients.

Adult↗
PubMed2006

Usefulness of LigaSure for liver resection: analysis by randomized clinical trial.

BACKGROUND: The goal of the present study was to evaluate the efficacy of the novel LigaSure Vessel Sealing System (Valleylab, Boulder, CO) when used for liver resection. METHODS: Sixty patients (n = 30 in each group) with liver pathology from a single center were randomized to undergo liver resection with either the LigaSure system or with conventional clamping methods. Patients were stratified according to tumor size (<5 or >5 cm), type of hepatectomy (minor or major), and liver damage (normal or injured). Estimated blood loss during liver transection was used as the primary end point, whereas liver transection speed and morbidity rate were used as secondary end points. RESULTS: There were no hospital deaths. The median blood loss during liver transection was less in the LigaSure than in the conventional group (200 vs 322 mL; P = .185). The amount of blood loss during minor hepatectomy was significantly less in the LigaSure than in the conventional group (186 vs 412 mL, P = .012). The liver transection speed was significantly faster in the LigaSure than in the conventional group (2.3 vs 1.6 cm(2)/min, P < .001. The number of ties required during liver transection was significantly less in the LigaSure than in the conventional group (6 vs 69 ties, P < .001). The morbidity rate was similar when comparing the 2 groups, indicating that the LigaSure sealing device and conventional methods had comparable efficacy in sealing the bile duct in the portal triad. Postoperative bile leak was observed in 1 patient (3%) in the LigaSure group and in 3 patients (9%) in the conventional group (P = .301). CONCLUSIONS: The LigaSure system is an effective and safe tool for decreasing liver resection time.

Aged↗
PubMed2006

[Influence of primary disease factors on outcome after resection of colorectal liver metastases?].

The outcome after resection of hepatic metastases from colorectal cancer is influenced not only by factors of metastatic lesions but also those of primary disease. To clarify whether primary disease factors are predictive of post-resection outcome of colorectal liver metastases, 180 patients (male : female = 114 : 66; 61.1 +/-10.5 yrs; synchronous: metachronous = 95 : 85; colon: rectum = 124 : 56 who underwent surgery of colorectal liver metastases in Cancer Institute Hospital from 1995 to 2005 were recruited for analysis. Post-resection outcome of the patients with colorectal liver metastases was significantly influenced by 1) depth of invasion, 2) grade of lymph node metastasis , 3) number of metastatic lymph nodes and 4) Dukes stage of primary disease. The patients with lymph node metastases further than grade 3 showed median survival time of less than 2 years and did not survive longer than 5 years. Thus such condition seemed not warrant resective treatment for liver metastases. In case of synchronous metastatic disease, primary disease information, such as lymph node metastases, depth of invasion, and Dukes stage, were significant predictive factors after hepatectomy. Meanwhile, such factors did not show significant influence in the patients with metachronous liver metastases. In conclusion, influence of primary disease factors should be considered for deciding the indication of hepatectomy for colorectal liver metastases, especially when patients have synchronous lesions.

Colorectal Neoplasms↗
PubMed2006

[Cancer board--new medical system in cancer clinic].

To proceed with more patient-oriented cancer medicine, the development of a new medical system is necessary in Japan. In Ariake Hospital of the Japanese Foundation for Cancer Research, a new medical system has been developed, which is composed of a common outpatient clinic and a conference system. The core conference system is called "Cancer Board". The practice of patient-oriented medicine in gastroenterological cancer has been introduced as a sample of the Cancer Board system in our hospital.

Ambulatory Care Facilities↗
PubMed2005

Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma.

We identified that suppressor of cytokine signaling-3 (SOCS-3) gene was aberrantly methylated in its CpG island in three of 10 human hepatocellular carcinoma (HCC) cell lines. SOCS-3 RNA was undetectable in five of the 10 HCC cell lines including the three methylated cell lines, and a demethylating agent, 5-aza-2'-deoxycytidine, reactivated SOCS-3 expression in three cell lines tested. The DNA region where we found aberrant DNA methylation includes a signal transducers and activators of transcription (STAT) binding consensus sequence. When the DNA region was used as a promoter, DNA methylation markedly reduced promoter activity. SOCS-3 was also aberrantly methylated in six of 18 primary HCC samples. SOCS-3 expression was reduced in three of the three methylated and one of the three unmethylated primary samples examined. Restoration of SOCS-3 in cells lacking SOCS-3 expression suppressed STAT3 phosphorylation and cell growth. We found that IL-6 acted as a growth factor in HCC cells. Inhibition of SOCS-3 expression in cells whose growth was induced by IL-6 enhanced STAT3 phosphorylation and cell growth. In addition, AG490, a chemical JAK2 inhibitor, suppressed cell growth and downregulated STAT3 phosphorylation, but not FAK phosphorylation. We also found that SOCS-3 physically interacted with phosphorylated FAK and Elongin B in HCC cells. Restoration of SOCS-3 decreased FAK phosphorylation as well as FAK protein level. Inhibition of SOCS-3 expression increased FAK phosphorylation, resulting in enhancement of cell migration. These data indicate that SOCS-3 negatively regulates cell growth and cell motility by inhibiting Janus kinase (JAK)/STAT and FAK signalings in HCC cells. Thus, loss of SOCS-3 by the associated DNA methylation confers cells advantage in growth and migration.

Carcinoma, Hepatocellular↗
PubMed2005

Clinicopathology of pancreaticobiliary maljunction: relationship between alterations in background biliary epithelium and neoplastic development.

BACKGROUND/PURPOSE: Between 1988 and 2003, 38 patients underwent biliary resection for pancreaticobiliary maljunction (PBM). We reviewed the histopathologic findings for the surgically resected specimens to compare the clinical and pathologic features and assess the relationship between changes in the background biliary epithelium and the development of neoplasms. METHODS: Papillary hyperplasia (PHP) seen in the biliary epithelium of patients with PBM, was classified into grades 0--III in the gallbladder and grades 0--II in the extrahepatic bile duct, according to the extent, and was assessed for links with tumors in the same specimens. RESULTS: The incidence of gallbladder carcinoma was 13/21 in grades I--II, versus 0/16 in grade III, while the incidence of bile duct carcinoma was 4/20 in grade I versus 0/5 in grade II. Furthermore, these incidences for patients below age 50 years and age 50 or older were 1/18 versus 12/20, and 0/14 versus 6/17, respectively. CONCLUSIONS: PHP of the biliary epithelium in PBM patients is an important precursor lesion, especially for gallbladder cancer, and the risk becomes greater with age, regardless of the type of pancreatobiliary junction (PBJ) and its location in the biliary tract.

Adolescent↗
PubMed2005

Image-diagnostic features of mature cystic teratomas of the pancreas: report on two cases difficult to diagnose preoperatively.

This report documents the findings of two rare cases of mature cystic teratoma of the pancreas. Although they could not be diagnosed preoperatively, our retrospective report suggests that the combined diagnosis of ultrasonography (US), enhanced computed tomography (CT), and magnetic resonance cholangiopancreatography (MRCP) might allow differentiation from other cystic lesions such as mucinous cystic tumors (MCTs) and intraductal papillary-mucinous tumors (IPMTs). Since the cystic teratomas were both filled with keratinous and sebaceous material, they were echogenic, appearing as solid masses on US. Enhanced CT showed their cystic nature, with values slightly higher than water, and MRCP revealed defects of internal signals.

Female↗
PubMed2005

[Appliance of microarray technology to clinical organ transplantation].

Although recent advances in immunosuppressive therapy have dramatically enhanced the early survival of solid organ transplant recipients, acute rejection still occurs in some recipients. Long-term immunosuppressive drug administration, furthermore, entails a number of potentially significant problems such as infection, spontaneous neoplasm and drug toxicity. Alloantigen specific tolerance induction is the ultimate goal in transplant immunology, and can be induced in a rodent model; however, the precise mechanism by which specific tolerance is affected are not clearly understood, and the current immunosuppression regimens have all failed to achieve this goal in a clinical setting. DNA microarray technology has made it possible to analyze the expression of a large number of genes and revolutionized many areas of biology and medicine. This new technology can provide non-biased, global expressions of tens of thousands of genes simultaneously. Recent studies on gene expression profiles in various diseases, including allograft rejection, have successfully provided important information and new insights into the biological mechanisms of these diseases. In this article, we reviewed these insights, especially with the viewpoint of appliance of microarray technology to clinical solid organ transplantation.

Animals↗
PubMed2004

Antimonocyte chemoattractant protein-1 gene therapy attenuates graft vasculopathy.

OBJECTIVE: Accelerated coronary arteriosclerosis remains a major problem in the long-term survival of cardiac transplant recipients. However, the pathogenesis of graft vasculopathy is poorly understood, and there is no effective therapy. Transplant arteriosclerosis is characterized by early mononuclear cell attachment on the transplanted vessel followed by development of concentric neointimal hyperplasia. Early and persistent expression of monocyte chemoattractant protein-1 (MCP-1) in cardiac allografts has been implicated for the pathogenesis of transplant arteriosclerosis. METHODS AND RESULTS: We investigated whether anti-MCP-1 gene therapy can inhibit the development of intima hyperplasia in a mouse model of cardiac transplantation. Either the dominant-negative form of MCP-1 (7ND) or control vector was transfected into the skeletal muscles of B10.D2 mice. Cardiac allografts from DBA/2 mice were transplanted heterotopically into B10.D2 mice. 7ND gene transfer was associated with a significant reduction of the number of mononuclear cells accumulating in the lumen of the graft coronary arteries at 1 week and an attenuation of the development of the lesion at 8 weeks (intima/media ratio 0.79+/-0.05 versus 0.48+/-0.04). CONCLUSIONS: The MCP-1/chemokine receptor 2 (CCR2) signaling pathway plays a critical role in the pathogenesis of graft vasculopathy. This new anti-MCP-1 gene therapy might be useful to treat graft vascular disease.

Animals↗
PubMed2004

Reconstruction of hepatic or portal veins by use of newly customized great saphenous vein grafts.

BACKGROUND AND AIMS: Segmental resection of major hepatic veins or the portal vein is sometimes required if one is to secure adequate surgical margins from hepatic or pancreatic malignancies. An external iliac vein is widely sacrificed as a vein graft to replace the defect, but this is associated with postoperative edema of the lower leg. We developed a new method for constructing the great saphenous vein to interpose the hepatic or portal veins. PATIENTS AND METHODS: The great saphenous vein was divided transversely into three sections, which were aligned side-to-side. The three pieces were anastomosed to make a sheet 3 x 2 cm, which was rolled up into a cylindrical form of approximately 1 cm in diameter and 2 cm in length. We applied the finished vein grafts to interpose the major hepatic veins in three patients with metastatic liver tumors and the portal vein in two patients with pancreatic malignancies in cylindrical form and to reconstruct the portal vein in one patient with a pancreas cancer, using a three-row sheet as a patch graft. RESULTS: No patient developed venous thrombosis of the graft or edema of the lower leg. CONCLUSIONS: The newly customized vein graft was safe and useful for the reconstruction of the major hepatic or portal veins.

Aged↗
PubMed2004

[Primary duodenal carcinoma].

Primary duodenal carcinoma (PDC) is rare and generally considered to have a low resectability rate and dismal prognosis. PDCs as well as other carcinomas in the pancreatic head are treated by curative pancreaticoduodenectomy. In a selected patient, segmental resection or local resection of the duodenum is indicated. Early PDC can be treated by endoscopic resection. There is an increased risk in patients with familial adenomatous polyposis and adenomas in the duodenum.

Adenomatous Polyposis Coli↗
PubMed2003

Identification of gene expression profile in tolerizing murine cardiac allograft by costimulatory blockade.

The induction of specific tolerance would be the ultimate achievement in transplant immunology, but the precise mechanisms of immunologic tolerance remain largely unknown. Here, we investigated global gene expression analysis in tolerizing murine cardiac allografts by means of oligonucleotide microarrays. Tolerance induction was achieved in cardiac allografts from BALB/c to C57BL/6 mice by daily intraperitoneal injection of anti-CD80 and anti-CD86 monoclonal antibodies (mAbs). Comparative analysis revealed 64 genes to be induced more extensively in the tolerizing than in the syngeneic isografts, and 16 genes than in the rejecting allografts. Two genes were specifically upregulated in the tolerizing allografts. In the tolerizing allografts there were induced marked expressions of a number of genes for pro-inflammatory factors, including interferon-gamma-inducible cytokines and chemokines, as well as apoptosis-related genes, which were also upregulated in the rejecting allografts. Moreover, these gene expression patterns continued to be upregulated more than 70 days posttransplant. These results provide evidence that immunologic tolerance can be induced and maintained in the presence of prominent pro-inflammatory gene expression in vivo.

Animals↗
PubMed2003

Little evidence for cell fusion between recipient and donor-derived cells.

Despite recent advances in immunosuppressive therapy, accelerated coronary atherosclerosis remains a major problem in the long-term survival of cardiac transplant recipients. However, the pathogenesis of the transplant-associated atherosclerosis remains largely unknown. Here, we investigated the origin of the vascular cells that contribute to graft vasculopathy. We performed heterotopic heart transplantation using genetically modified mice that express LacZ or green fluorescent protein (GFP) ubiquitously and constitutively. At 4 weeks after transplantation, the graft coronary arteries developed neointimal hyperplasia, expressing several smooth muscle cell markers. Most of the neointimal cells were composed of recipient cells but not graft medial smooth muscle cells. We seldom detected neointimal cells that were positive for both LacZ and GFP. When we transplanted wild-type cardiac allografts into the chimeric mice whose bone marrow cells had been replaced with those of LacZ-mice or GFP-mice, we observed that most of the neointimal cells were derived from the bone marrow. These findings suggest that recipient bone marrow-derived cells contribute to the pathogenesis of graft arteriosclerosis. Spontaneous cell fusion between recipient and donor-derived cells seems to be a rare event, if it occurs at all.

Animals↗
PubMed2003

Risk factors for acute rejection in living donor liver transplantation.

The influence of human leukocyte antigen (HLA) compatibility and lymphocytotoxic crossmatch on acute rejection in living donor liver transplantation (LDLT) has not been well examined. We analyzed 100 consecutive adult LDLT cases. The patient and graft survival rates and post-operative complications were assessed. The relation between the incidence of acute rejection and some clinical factors including HLA and lymphocytotoxic matching was also examined. Patients with HLA DR zero mismatching (p = 0.02) or negative T-lymphocytotoxic crossmatch (p = 0.04) had a significantly lower chance of rejection within 6 wk after LDLT. However the results had no influence on the patient survival. Our results demonstrate that in LDLT, a graft from an HLA-DR zero mismatching or negative T-lymphocytotoxic crossmatch might be advantageous because of the decreased probability of early acute rejection.

Acute Disease↗
PubMed2003

Effect of apolipoprotein E polymorphism on bile lipid composition and the formation of cholesterol gallstone.

OBJECTIVE: It remains a matter of controversy whether possession of the apolipoprotein E4 (apoE4) allele is a genetic risk factor for the formation of cholesterol gallstones. The aim of the present study was to test this hypothesis by investigating the effect of apoE4 on bile lipid composition in normal subjects and in patients with cholesterol gallstones and to evaluate the distributions of apoE alleles in these two groups. METHODS: The study population consisted of 79 patients who underwent open or laparoscopic cholecystectomy for symptomatic cholesterol gallstone disease. The control group (n = 53) included 11 patients with benign gallbladder polyps and 42 normal subjects acting as donors in living donor liver transplantation. The apoE genotypes were assessed by dot blot hybridization with digoxigenin-labeled probes. Bile lipid composition was determined by enzymatic assays and high performance liquid chromatography. RESULTS: Bile lipid composition and cholesterol saturation index (CSI) were similar in the control subjects harboring the apoE4 allele and those without apoE4 (mean CSI, 85.9% and 72.2%, respectively, p = 0.69). Likewise, in the cholesterol gallstone patients, bile lipid composition and CSI were similar in the patients with and without apoE4 allele (mean CSI, 134.9% vs 152.2%, p = 0.6). Furthermore, the prevalence of the apoE4 allele was similar in the patients with cholesterol gallstones and in the control group (8.5% vs 7.6%, p = 0.46, OR = 0.88; 95% CI = 0.64-1.22). CONCLUSIONS: The apoE4 allele is not a contributory factor to cholesterol gallstone formation, at least in the Japanese population.

Adult↗
PubMed2002

Gene expression profile during acute rejection in rat-to-mouse concordant cardiac xenograft by means of DNA microarray.

Using a rat-to-mouse concordant cardiac transplantation model and DNA microarrays, we studied the gene expression profiles during acute rejection. We used inbred BALB/c and C3H/He mice and Lewis rats for our study, in which heterotopic cardiac transplantations were performed. Total RNA was isolated from xenografts (Lewis to C3H), allografts (BALB/c to C3H), rat isografts (Lewis to Lewis) and mouse isografts (C3H to C3H) on day 5 following transplantation. We screened for gene expression profiles in the xenografts, allografts, and mouse isografts by means of DNA microarrays. With a murine array, we determined that many IFN-gamma inducible genes were profoundly expressed in both the allografts and xenografts relative to the isografts. Mac-1 was specifically induced in the xenografts relative to the allografts. Using a rat array, we observed that the cardionatrin and atrial natriuretic factors were most profoundly expressed in the xenografts in comparison with the rat isografts. In addition to known genes, many expressed sequence tags were induced in the xenografts. We identified a group of genes, including Mac-1 induced specifically in xenografts, as well as many new genes upregulated in xenografts.

Acute Disease↗
PubMed2002

Detection of an up-regulation of a group of chemokine genes in murine cardiac allograft in the absence of interferon-gamma by means of DNA microarray.

BACKGROUND: [corrected] Interferon (IFN)-gamma and the IFN-gamma-dependent pathway are prominent in vascularized allograft during acute rejection. However, IFN-gamma deficient (IFN-gamma-/-) mice can rapidly reject cardiac allografts. To bring the alternative pathway during allograft rejection into more precise focus, we investigated the gene expression profile in murine cardiac allografts in IFN-gamma-/- mice by means of DNA microarray. MATERIAL AND METHOD: We screened for gene expression changes in murine cardiac allografts of BALB/c H-2d into both wild-type C57BL/6 H-2b (n=3) and IFN-gamma-/- C57BL/6 H-2b(IFN-gamma-/-, n=4) using Affymetrix oligonucleotide arrays to monitor more than 11,000 genes and expressed sequence tag (ESTs). The heart was heterotopically transplanted. Transplanted hearts were harvested on day 5. As a control, isografts (C57BL/6 to C57BL/6) were also harvested on day 5. RESULTS: On day 5, 64 of the 84 genes induced in the allografts in wild-type mice were not up-regulated in IFN-gamma-/- mice. We identified a group of 54 genes that were up-regulated in allografts in IFN-gamma-/- mice. Several chemokine genes, including monocyte chemoattractant protein=1 and macrophage inflammatory protein, were induced in the allografts in both wild-type and IFN-gamma-/- mice. Interestingly, a group of genes, including C10-like chemokine and platelet factor 4, were specifically induced in the IFN-gamma-/- mice. CONCLUSION: DNA microarray analysis reveals a unique pattern of mRNA expression in allografts in IFN-gamma-/- mice as well as a group of genes induced in cardiac allografts in both wild-type and IFN-gamma-/- mice, including monocyte chemoattractant protein-1 and monocyte chemoattractant protein-1.

Animals↗