Biomedical subjects

Michiaki Matsushita

Publications and source records attributed to Michiaki Matsushita.

At least 19 recordsLinked to original sources

PubMed2006

IL-1 and IL-6 induce hepatocyte plasminogen activator inhibitor-1 expression through independent signaling pathways converging on C/EBPdelta.

To elucidate signaling pathways activated by IL-1 and IL-6 that contribute to increased expression of plasminogen activator inhibitor-1 (PAI-1), we studied human hepatoma (HepG2) cells and primary mouse hepatocytes. HepG2 cell PAI-1 mRNA increased in response to IL-1beta, IL-6, and IL-1beta plus IL-6 as shown by real-time PCR. Activity of the transiently transfected PAI-1 promoter (-829 to +36 bp) increased as well. Systematic promoter deletion assays showed that the region from -239 to -210 bp containing a putative CCAAT-enhancer binding protein (C/EBP) binding site was critical. Point mutations in this region abolished the IL-1beta and IL-6 responses. Antibody interference electrophoretic mobility shift assays showed that C/EBPdelta (but not C/EBPalpha or C/EBPbeta) binding and protein were increased by IL-1beta, IL-6, and IL-1beta plus IL-6 in HepG2 cells. IL-1beta and IL-6 increased expression of both PAI-1 mRNA and C/EBPdelta mRNA in mouse primary hepatocytes as well. Downregulation of C/EBPdelta induced with small interfering RNA (siRNA) decreased secretion of PAI-1. As judged from results obtained with inhibitors, signal transduction in all three of the mitogen-activated protein kinase pathways was involved in IL-1-inducible PAI-1 expression. By contrast, JAK signaling was responsible for the IL-6-induced inducible expression. Thus IL-1 and IL-6 exert directionally similar effects on PAI-1 expression, but the induction involves distinct signaling pathways with a final common mediator, C/EBPdelta.

Animals↗

PubMed2006

Preoperative evaluation of hepatic vasculature by three-dimensional computed tomography in patients undergoing hepatectomy.

BACKGROUND: Hepatectomy is particularly difficult when the tumor is large, close to the inferior vena cava or the main trunk of the hepatic or portal vein, or in the caudate lobe, as well as when the operation is a re-hepatectomy, because two-dimensional computed tomography (CT) often does not clearly show tumor location relative to blood vessels. STUDY DESIGN: To evaluate the efficacy of three-dimensional computed tomography (3D-CT), reconstructed from multidetector-row computed tomography (MD-CT) with contrast, MD-CT was performed in 17 patients before hepatectomy. RESULTS: The third-order branches of the hepatic artery and the portal vein were clearly shown in all cases. Both the hepatic vein, which drained the same segment that the portal vein fed, and the portal vein were also clearly shown. These vessels could be visualized from any perspective. In 2 patients who underwent hemihepatectomy, large tumors (23.0 and 17.0 cm) displaced the vasculature, but the positions of tumor and vessels could be precisely evaluated by 3D-CT. In patients who required replacement of the vena cava with synthetic grafts, the distance and direction of pressure to IVC by tumor was accurately estimated by 3D-CT. In patients who were limited to segmentectomy or partial hepatectomy because of prior hepatectomy or tumor position, evaluation of the glissons was facilitated by 3D-CT. CONCLUSIONS: Three-dimensional-CT was extremely useful for preoperative simulation because it provided important information that could not be obtained with 2D-CT.

Adolescent↗

PubMed2006

Living-donor liver transplantation for hepatocellular carcinoma.

Transplant surgeons have long dreamed of achieving a complete cure for hepatocellular carcinoma (HCC) by replacing the liver with a new graft. Although the early results of liver transplantation for HCC were disappointing, with 5-year survival less than 40%, improved results in patients who met the so-called Milan criteria rekindled the enthusiasm for the treatment of HCC with liver transplantation. Furthermore, the recent development of living-donor liver transplantation in adults has allowed timely grafting for HCC patients and tentative expansion of the criteria for transplant candidacy in patients with HCC - although such expansion is fraught with controversy. Identification of a noninvasive marker that could predict the biological behavior as well as the prognosis of HCC would indeed be a major breakthrough.

Adult↗

PubMed2006

Hepatopulmonary fistula caused by alveolar echinococcosis: report of a case.

Alveolar echinococcosis is a parasitosis endemic to red fox habitats in the northern hemisphere. The liver is the most commonly affected organ, followed by the lungs. We report the case of an elderly woman with hepatic alveolar echinococcosis (HAE) complicated by a hepatopulmonary fistula. We performed a one-stage operation for the hepatic and pulmonary lesions through the transdiaphragmatic route via a laparotomy. We report this case to emphasize that the first-line treatment for a hepatopulmonary fistula caused by HAE should be radical surgery, which results in relief of symptoms and a good outcome.

Aged↗

PubMed2006

Pulmonary resection for metastases from hepatocellular carcinoma: factors influencing prognosis.

OBJECTIVE: Although the lung is the most common site of extrahepatic spread from hepatocellular carcinoma, outcomes after pulmonary resection and prognostic factors have not been well described. We analyzed a single-center experience with 25 patients undergoing pulmonary resection of metastases from hepatocellular carcinoma to examine the clinical factors and outcomes. METHODS: Patients were candidates for resection if they had controlled intrahepatic disease with no evidence of extrathoracic lesions and if all gross tumors could be removed with preservation of respiratory function. Twenty-five patients with hepatocellular carcinoma who underwent curative hepatectomy were suitable for the pulmonary resection criteria between 1990 and 2005. Clinical features and outcomes were analyzed. RESULTS: The mean actuarial 1-, 3-, and 5-year survivals after pulmonary resection were 80%, 61%, and 36%, respectively. Tumor number (solitary or multiple) and location (unilateral or bilateral lung) did not significantly affect cancer-specific survival. Mean 5-year survival was 25% for patients with disease-free interval of 1 to 11 months and 62% for those with disease-free interval of 12 months or more. Mean survival was 15.9 months for patients with alpha-fetoprotein of 500 ng/mL or more, and 39.2 months for those with alpha-fetoprotein less than 500 ng/mL. Five-year survival was 21% for patients with short disease-free interval or high alpha-fetoprotein level and 74% for those with long disease-free interval and low alpha-fetoprotein level (P = .015). CONCLUSION: Pulmonary resection for metastases from hepatocellular carcinoma may prolong survival in selected patients. Disease-free interval greater than 12 months and alpha-fetoprotein less than 500 ng/mL are important prognostic factors.

Adult↗

PubMed2006

Transduction of exogenous constitutively activated Stat3 into dispersed islets induces proliferation of rat pancreatic beta-cells.

In vitro proliferation of functional islet mass/beta-cells by transduction of cell cycle regulatory genes has not been well documented due to the lack of either an effective method for gene transduction to islets or effective genes for beta-cell proliferation. Signal transducers and activators of transcription- 3 (Stat3) are among the most important molecules for cell proliferation and for cell antiapoptosis. In this study, adenovirus-mediated gene transduction was performed on dispersed islet cells, and reaggregated islet mass functions, such as capabilities for reaggregation, proliferation, and glucose- stimulated insulin secretion (GSIS), were evaluated. The constitutively activated form of Stat3 (Stat3-C) was effectively transduced to most of the islet cells, even at a low density of adenovirus vector. There was no difference in the spontaneous reaggregation capability between Stat3-C transduced and control islet cells. BrdU incorporation in Stat3-C-transduced islet cells was significantly higher (2.8-fold) than that in the control cells, and it was significantly elevated (4-fold) by the addition of HGF in culture media. GSIS in Stat3-C-transduced islet cells was preserved to the level in controls by 5 days in culture. The results indicated that gene transduction into islet cells could be enhanced by first dispersing the cells. Stat3-C induced cell proliferation of beta-cells without loss of insulin secretion activity at the glucose challenge, and HGF enhanced the beta-cell proliferative activity of Stat3-C.

Adenoviridae↗

PubMed2006

AFP mRNA detected in bone marrow by real-time quantitative RT-PCR analysis predicts survival and recurrence after curative hepatectomy for hepatocellular carcinoma.

OBJECTIVE: To determine whether detection of hepatocellular carcinoma (HCC) cells by real-time quantitative RT-PCR targeting of alpha-fetoprotein mRNA (AFP mRNA) before or after curative hepatectomy predicts HCC recurrence and patient survival. SUMMARY BACKGROUND DATA: The presence of cancer cells in peripheral blood and/or bone marrow in patients with malignant disease has been reported to correlate with outcome. METHODS: Between July 2000 and June 2005, 136 consecutive HCC patients underwent primary curative hepatectomy. Bone marrow aspirated preoperatively, and peripheral blood samples collected before and after operation were subjected to real-time quantitative RT-PCR analysis using AFP mRNA as a target molecule. Median follow-up was 23 months (range, 6-54 months). Patient survival (PS), disease-free survival (DFS), and clinicopathologic features were compared between patients with positive and negative AFP mRNA. RESULTS: Twenty-four patients died (22 from HCC). HCC recurred in 66 patients (hepatic in 37 [56.1%]; hepatic and remote in 17 [25.8%], and remote alone in 12 [18.2%]). Bone marrow was positive for AFP mRNA in 38 patients (27.9%) and negative in 98 (72.1%). One- and 3-year PS was 96.6% and 91.4%, respectively, with negative AFP mRNA versus 86.2% and 55.5%, respectively, with positive AFP mRNA (P < 0.0001). One- and 3-year DFS were 73.2% and 44.8%, respectively, with negative AFP mRNA versus 54.5% and 25.8%, respectively, with positive AFP mRNA (P = 0.0399). Portal vascular invasion, tumor size, multiple tumors, and tumor differentiation correlated with inferior PS and DFS on univariate analysis. On multivariate analysis, positive AFP mRNA was the most important risk factor for PS (P = 0.001) and DFS (P = 0.0165). In addition, positive AFP mRNA in peripheral blood after operation tended to predict reduced DFS. CONCLUSION: AFP mRNA in the bone marrow and systemic circulation during the perioperative period predicts patient survival and recurrence after curative hepatic resection for HCC.

Biomarkers, Tumor↗

PubMed2005

Lipid peroxidation during ischemia depends on ischemia time in warm ischemia and reperfusion of rat liver.

Prolonged hepatic warm ischemia has been incriminated in oxidative stress after reperfusion. However, the magnitude of oxidative stress during ischemia has been controversial. The aims of the present study were to elucidate whether lipid peroxidation progressed during ischemia and to clarify whether oxidative stress during ischemia aggravated the oxidative damage after reperfusion. Rats were subjected to 30 to 120 min of 70% warm ischemia alone or followed by reperfusion for 60 min. Lipid peroxidation (LPO) was evaluated by amounts of phosphatidylcholine hydroperoxide (PC-OOH) and phosphatidylethanolamine hydroperoxide (PE-OOH) as primary LPO products. Total amounts of malondialdehyde and 4-hydroxy-2-nonenal (MDA + 4-HNE), degraded from hydroperoxides, were also determined. PC-OOH and PE-OOH significantly increased at 60 and 120 min ischemia with concomitant increase of oxidized glutathione. These hydroperoxides did not increase at 60 min reperfusion after 60 min ischemia, whereas they did increase at 60 min reperfusion after 120 min ischemia with deactivation of phospholipid hydroperoxide glutathione peroxidase and superoxide dismutase. The amount of MDA + 4-HNE exhibited similar changes, but the velocity of production dropped with ischemic time longer than 60 min. In conclusion, oxidative stress progressed during ischemia and triggered the oxidative injury after reperfusion. Secondary LPO products are less sensitive, especially during ischemia, which may cause possible underestimation and discrepancy.

Aldehydes↗

PubMed2005

Number of lymph node metastases is a significant prognostic factor in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (IHCC) is a rare primary hepatic tumor. Outcomes after resection and the use of lymph node dissection have not been well described. From a prospective database, we identified 53 patients with IHCC who underwent exploration between April 1983 and March 2004. Hepatic resection was performed in 44 patients, 30 of whom underwent lymph node dissection. Clinicopathological features and outcomes were analyzed. The actuarial 1-year survival was 66.2% in resected patients, compared to 0% in unresectable patients (p < 0.0001), with a 50% overall survival of 21.5 months and 3.1 months, respectively. The actuarial 3-year and 5-year overall survival rates in resected patients were 38.3% and 26.3%, respectively. Univariate analysis revealed that factors associated with poor overall survival included multiple tumors, extrahepatic bile duct involvement, noncurative resection, and involvement of lymph nodes. Multivariate analysis in resected patients revealed that multiple tumors (p < 0.0074) and non-curative resection (p = 0.0068) were significant risk factors for poor overall survival. The survival rate in patients with three or more positive nodes was significantly lower than in those with fewer than three (p < 0.0001). Three patients with solitary tumors and one or two involved lymph nodes have survived beyond 4 years after extended lobectomy with systemic lymphadenectomy. Curative resection, single tumor, and fewer than two lymph node metastases were prognostic factors for good outcome. Curative resection with lymph node dissection improved survival in patients with no more than two positive lymph nodes.

Adult↗

PubMed2005

Laparoscopic hepatectomy with the hook blade of ultrasonic coagulating shears and bipolar cautery with a saline irrigation system.

BACKGROUND: The number of patients who have undergone laparoscopic hepatectomy is small, and the operative procedure is not yet well established. METHODS: We performed laparoscopic hepatectomy in eight patients, using the hook blade of ultrasonic coagulating shears, and bipolar cautery with a saline irrigation system, with minilaparotomy. The operative time, blood loss, and postoperative hospital stay of patients with laparoscopic left lateral segmentectomy were compared with these parameters in ten patients who had had a left lateral segmentectomy with laparotomy. RESULTS: The laparoscopic hepatectomies included seven left lateral segmentectomies and one nonanatomical partial resection of the lateral segment. The mean duration of the operation in these eight patients was 181.1 +/- 44.6 min. The mean amount of blood loss was 177.6 +/- 129.1 ml. Postoperative complications consisted of two cases of bleeding. The mean postoperative hospital stay in all eight patients was 9.88 +/- 4.36 days. The mean duration of operation (185.9 +/- 46.0 min) and mean postoperative hospital stay (9.47 +/- 4.61 days) in the seven patients with laparoscopic left lateral segmentectomies were significantly shorter than these parameters (255.7 +/- 59.4 min and 24.6 +/- 8.82 days) in the ten patients who had had left lateral segmentectomies with laparotomy. The mean amount of blood loss (160.0 +/- 128.9 ml) in the laparoscopic series was less than that (318.5 +/- 192.2 days) in the patients who had had laparotomy. CONCLUSIONS: Laparoscopic hepatectomy with the ultrasonic coagulating shears and bipolar cautery with minilaparotomy was safe, and less invasive than the open procedure, for minor hepatectomy procedures such as left lateral segmentectomy.

Aged↗

PubMed2004

Cadaveric domino liver transplantation: the first case in Japan.

The first case of domino liver transplantation from a brain-dead donor in Japan is described. A 49-year-old man with familial amyloidotic polyneuropathy received a cadaver liver, and his native liver was transplanted into a 53-year-old man with polycystic liver and kidney disease. The cadaveric liver allograft was transplanted by the conventional technique. The graft taken from the first recipient had four outflow orifices (the left, middle, and right hepatic veins, and upper vena cava), for which a single orifice was created at the back table. This graft was transplanted in piggy-back fashion. The first recipient developed acute rejection on day 13 and hepatic artery stenosis on day 36. These were treated by steroid recycle therapy and percutaneous transarterial angioplasty. He was discharged on day 57 with normal liver function. The second recipient underwent re-operation for bleeding from the right adrenal gland and left thoracic cavity. He was diagnosed with acute rejection on day 7, which was treated by steroid pulse therapy. He was discharged uneventfully on day 39 with normal liver function.

Amyloid Neuropathies, Familial↗

PubMed2004

[Liver regeneration in living-donor liver transplantation].

Liver regeneration in living-donor liver transplantation is summarized from the authors' data. In donors, liver function tests recovered to within the normal range 2 weeks after surgery regardless of graft type. At 2 weeks, the volumetric recovery of the remnant liver was 65% and 80% of the original volume in right and left lobe donors, respectively. These results suggest that functional recovery occurs earlier than morphologic restoration in donors. In recipients, the factor that affected the regeneration rate in size 4 weeks after transplantation was only implanted graft size; the rate was greater in patients in whom smaller grafts were implanted. In recipients with a rate of two or more, however, high portal vein pressure and flow were observed. Further, persistent low platelet counts and hyperbilirubinemia were seen in those patients. These results indicate that size enlargement may be caused by engorgement, and functional recovery is not achieved concurrently with morphologic restoration, especially in patients with smaller grafts. In patients with fulminant hepatic failure who receive auxiliary partial orthotopic liver transplantation, sequential histopathologic observations of the diseased liver revealed that liver regeneration initiates from cytokeratin 17-positive ductules and at least 1 year is necessary for complete recovery.

Hepatocytes↗

PubMed2004

[In vitro chemosensitivity test for hepatocellular carcinoma using collagen-gel droplet embedded cultures].

This study evaluated an in vitro assay for chemosensitivity test using a collagen-gel droplet-embedded culture drug sensitivity test (CD-DST) for hepatocellular carcinoma (HCC). In 25 patients with HCC, in vitro chemosensitivity to 5-fluorouracil (5-FU), epirubicin (EPI), and cisplatin (CDDP) was examined by CD-DST, and 5-FU, EPI, and paclitaxel (PTX) were examined in 38 patients with breast cancer. Successful rates of chemosensitive evaluation by CD-DST were 64% for HCC and 79% for breast cancers. Although chemosensitivities of breast cancer were 5-FU 23.1%, EPI 83.3%, and PTX 67.7%, only one HCC sample was sensitive to EPI. Growth rates of HCC for 7 days of culture were significantly lower than those of breast cancers (1.04 vs 3.61). The culture methods for HCC in CD-DST should be improved to estimate accurate results.

Antineoplastic Agents↗

PubMed2003

Feasibility of insertion/implantation of 2.0-mm-diameter gold internal fiducial markers for precise setup and real-time tumor tracking in radiotherapy.

PURPOSE: To examine the feasibility and reliability of insertion of internal fiducial markers into various organs for precise setup and real-time tumor tracking in radiotherapy (RT). MATERIALS AND METHODS: Equipment and techniques for the insertion of 2.0-mm-diameter gold markers into or near the tumor were developed for spinal/paraspinal lesions, prostate tumors, and liver and lung tumors. Three markers were used to adjust the center of the mass of the target volume to the planned position in spinal/paraspinal lesions and prostate tumors (the three-marker method). The feasibility of the marker insertion and the stability of the position of markers were tested using stopping rules in the clinical protocol (i.e., the procedure was abandoned if 2 of 3 or 3 of 6 patients experienced marker dropping or migration). After the evaluation of the feasibility, the stability of the marker positions was monitored in those patients who entered the dose-escalation study. RESULTS: Each of the following was shown to be feasible: bronchoscopic insertion for the peripheral lung; image-guided transcutaneous insertion for the liver; cystoscopic and image-guided percutaneous insertion for the prostate; and surgical implantation for spinal/paraspinal lesions. Transcutaneous insertion of markers for spinal/paraspinal lesions and bronchoscopic insertion for central lung lesions were abandoned. Overall, marker implantation was successful and was used for real-time tumor tracking in RT in 90 (90%) of 100 lesions. No serious complications related to the marker insertion were noted for any of the 100 lesions. Using three markers surgically implanted into the vertebral bone, the mean +/- standard deviation in distance among the three markers was within 0.2 +/- 0.6 mm (range -1.4 to 0.8) through the treatment period of 30 days. The distance between the three markers gradually decreased during RT in five of six prostate cancers, consistent with a mean rate of volume regression of 9.3% (range 0.015-13%) in 10 days. CONCLUSIONS: Internal 2.0-mm-diameter gold markers can be safely inserted into various organs for real-time tumor tracking in RT using the prescribed equipment and techniques. The three-marker method has been shown to be a useful technique for precise setup for spinal/paraspinal lesions and prostate tumors.

Adenocarcinoma↗

PubMed2003

[Echinococcosis].

Explore the source record for details and available documents.

Albendazole↗

PubMed2003

[Postoperative adjuvant intraarterial chemotherapy of combined cisplatin and 5-FU for advanced hepatocellular carcinoma].

Postoperative adjuvant intraarterial infusion chemotherapy was performed for 22 hepatectomized patients with Stage III and Stage IV-A hepatocellular carcinoma from July, 1997, to December, 1999. One course of this chemotherapy consisted of cisplatin (10 mg/body/day on days 1-5) followed by 5-FU (250 mg/body/day on days 1-5). One hundred forty-eight patients of Stage III and Stage IV-A underwent hepatectomy from 1992 to 2001 and were enrolled as historical control. There were 9 Stage III cases treated with this adjuvant chemotherapy, and there were 7 or 6 Stage IV-A cases with and without main portal thrombosis, respectively. Survival and disease-free survival curves were not improved compared to historical control by this adjuvant chemotherapy. The number of recurrences in the remnant liver of 2 Stage IV-A cases with main portal thrombosis was limited to 3. Those cases treated with rehepatectomy and transarterial chemoembolization survived about 1,200 days without tumor recurrence.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Control of intraoperative bleeding during liver resection: analysis of a questionnaire sent to 231 Japanese hospitals.

To determine the safest and most efficient way of performing hepatectomy, the differences in methods employed by Japanese surgeons were examined. In November 1998, a questionnaire on bleeding control during hepatectomy was sent to 270 hospitals located throughout Japan. The answers from 231 hospitals (85.6%) were analyzed. Surgical apparatus such as an ultrasonic dissector (USD) was used in 203 hospitals. Pringle's maneuver was performed routinely in 25%, for segmentectomy and subsegmentectomy in 25%, for lobectomy in 9%, depending on the situation in 34%, and never in 7%. In 135 hospitals (60%), hemostatic materials such as fibrin glue were always applied to the cut surface after hepatectomy. The USD was chosen and widely accepted by the hospitals studied. As Japanese patients with hepatoma often have liver cirrhosis, intermittent occlusion and the selective clamping of hepatic inflow were considered preferable to persistent inflow occlusion. The gentle exposure of hepatic venous branches, careful hemostasis during hepatectomy, and accurate location of the hepatic vein by intraoperative ultrasonography were all considered to be extremely important.

Attitude of Health Personnel↗

PubMed2002

A novel method for faster formation of rat liver cell spheroids.

Hepatocyte spheroids are expected to be the main component of the artificial liver bioreactor for their higher function. The preparation of hepatocyte spheroids, however, can require as many as 24 to 96 h. To reduce this time, we investigated a method employing a new technique of rat hepatocyte preparation and a dynamic culture. The modified Seglen's method for standard hepatocyte isolation was altered by elimination of ethyleneglycol bis(aminoethylether) tetraacetate from the first perfusate and calcium from the second perfusate. Isolated hepatocytes were cultured in a spinner flask by spinning at 120 rpm. The modified Seglen's method was used as a control. Cells obtained by the new method were more cohesive and formed a higher proportion of cell aggregates than control cells. In the spinning culture, hepatocytes had a tendency to aggregate and 80% of cells formed spheroids within 6 h of culturing. The mean size of spheroids was 68.5 +/- 18.5 microm. Confocal laser scanning microscopy revealed that individual spheroids contained approximately 30% of nonparenchymal cells over their surface. Using the new hepatocyte preparation method followed by a spinning culture, we were able to produce hepatocyte spheroids in as few as 6 h.

Animals↗