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Biomedical subjects

T Todoroki

Publications and source records attributed to T Todoroki.

At least 37 records · Page 2Linked to original sources
PubMed1999

Conformal irradiation for hepatobiliary malignancies.

The term 'conformal irradiation' is usually used to describe the delivery of sophisticated high dose external beam irradiation (EBRT) with the aid of 3-D treatment planning and the option of both coplanar and non-coplanar beams. Data will be presented from the University of Michigan which suggest that conformal high dose EBRT (48-72.6 Gy) can be used for intrahepatic cancers, both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC), to potentially increase local control and survival over what would be expected with lower dose EBRT. For purpose of this discussion, the term conformal irradiation will be expanded to include other techniques which conform the high dose irradiation boost volume in close proximity to unresected tumor or positive margins of resection. Data will be presented from series which utilize transcatheter iridium and intraoperative electron irradiation (IOERT) supplements to EBRT +/- concomitant chemotherapy. Each method intensifies treatment in an attempt to improve local control and survival.

Bile Duct Neoplasms↗
PubMed1999

Future role of radiotherapy as a component of treatment in biliopancreatic cancers.

For resected and unresectable pancreas cancers, data will be summarized from both adjuvant and locally unresectable pancreas cancer series (EBRT +/- IOERT) to demonstrate the justification of continuing to utilize chemo-irradiation as a component of treatment. The resultant improvements in local control with combined modality treatment, however, achieve only minimal improvements in survival in view of the high incidence of abdominal relapse (liver and peritoneal). Further improvement in survival may necessitate regional approaches for chemotherapy or may await advances in gene therapy. For locally unresectable and resected but residual bile duct malignancies, chemoirradiation appears to enhance tumor control and survival. Dose intensification of both modalities may be useful in improving disease control and survival. After chemoirradiation, the addition of liver transplant, in carefully selected patients who are unresectable with standard resection, may further enhance disease control and survival over what would be expected with either approach in isolation.

Biliary Tract Neoplasms↗
PubMed1999

[Chemoradiation therapy for advanced esophageal cancers--report of 3 cases].

Three cases of prominent-type advanced esophageal cancer were treated with chemoradiation therapy using a 5-FU analog and low dose CDDP. All cases showed a complete response after the treatment. Only mild bone marrow suppression was found in one case. This protocol will be applied for patients with prominent-type advanced esophageal cancers, especially high risk patients.

Aged↗
PubMed1998

Pancreatic carcinoma: correlation between E-cadherin and alpha-catenin expression status and liver metastasis.

BACKGROUND: Dysfunction of the E-cadherin/catenin-mediated cell-cell adhesion system has been associated with invasiveness and poor differentiation of human carcinomas. However, its importance in the genesis of liver metastasis has not been examined sufficiently. METHODS: A series of 26 primary pancreatic carcinomas and the concomitant liver metastases from 15 of them, obtained at autopsy, were analyzed for E-cadherin and alpha-catenin protein expression by immunohistochemistry. RESULTS: Both E-cadherin and alpha-catenin expression were preserved in 15 (58%) and reduced in 11 (32%) of the 26 primary pancreatic carcinomas. In the former 15 primaries, carcinoma cells were attached to each other tightly, whereas the latter 11 primaries showed isolated or loosely connected attachments. The metastatic ratio was higher in tumors exhibiting tight adhesion than in those with loose adhesion: 73% and 36%, respectively (P = 0.059). E-cadherin and alpha-catenin expression patterns in liver metastases basically followed those in the corresponding primaries (P < 0.01). CONCLUSIONS: Reduced E-cadherin and alpha-catenin expression in primary pancreatic carcinoma has no significant predictive value regarding the presence of liver metastasis. Rather, there is a greater tendency for liver metastasis in cases in which the integrity of the E-cadherin/catenin-mediated cell-cell adhesion system is intact.

Adult↗
PubMed1998

Impact of ischemia-reperfusion injury on dimensional changes of hepatic microvessels.

Dimensional alteration of hepatic microvessels was demonstrated during reperfusion after normothermic hepatic ischemia. Using a specially designed cover glass, it was possible to relocate selected sites of observation and microvessels repeatedly throughout the whole reperfusion time. Twenty minutes of hepatic ischemia resulted in a decrease of sinusoidal diameter (mean +/- SEM; 10.0 +/- 0.3 microns at baseline, 8.2 +/- 0.2 microns after ischemia) and diameter of postsinusoidal venules (26.4 +/- 1.2 at baseline, 23.0 +/- 1.0 after ischemia). In the control group (no ischemia induced) no changes of these parameters were observed. Thus, the reduction of hepatic microvascular cross section was present during the early phase of reperfusion. Hepatic dysfunction was characterized by increased serum activity of liver enzymes and reduction of bile flow in the ischemia-exposed animals. It has been suggested that postischemic dimensional microvascular changes are involved in postischemic liver dysfunction.

Animals↗
PubMed1998

Application of a novel method for subsequent evaluation of sinusoids and postsinusoidal venules after ischemia-reperfusion injury of rat liver.

Although several intravital fluorescence microscopic studies demonstrated that microcirculatory derangement is induced during liver ischemia-reperfusion, these data were obtained from randomly selected microvascular areas and microvessels. Repeated observation of the identical microvessels has not been performed yet. Using a specially designed cover glass, it is now possible to relocate desired sites of observation repeatedly over the whole reperfusion time. The aim of this study was to determine the impact of reperfusion time on hepatic microvascular perfusion state. Twenty minutes of ischemia induced a significant decrease in sinusoidal perfusion rate (29.1 +/- 10.2%) as compared with baseline values (98.0 +/- 0.3%). At 30, 60, and 120 min of reperfusion, the percentage of perfused sinusoids recovered to 62.8 +/- 6.6, 67.5 +/- 5.7, and 77.2 +/- 5.4%. The number of stagnant leukocytes in the same sinusoids was 6.2 +/- 1.9/lobule at baseline and increased to 22.3 3.6/lobule at 120 min of reperfusion. The number of leukocytes adhering within postsinusoidal venules was 53.5 12.5/mm2 before ischemia and increased to 414.2 62.5/mm2 at 120 min of reperfusion. We have demonstrated that during 120 min of reperfusion, there was a steady increase in both sinusoidal and venular leukocyte adhesion along with an attenuation of the initially severely depressed sinusoidal perfusion. A no-reflow phenomenon at an early phase of reperfusion and subsequent reflow were proven.

Animals↗
PubMed1998

The invasion potentials of human biliary tract carcinoma cell lines: correlation between invasiveness and morphologic characteristics.

The abilities of 9 kinds of human biliary tract carcinoma cell lines to invade through basement membrane or type I collagen were examined using an in vitro invasion assay system. The correlations between invasiveness and morphologic characteristics of the carcinoma cells in 3 dimensional collagen gel were also examined. most of the biliary tract carcinoma cell lines kept the abilities of glandular differentiation and basement membrane formation of the original tumor. Their invasiveness, however, correlated with the degree of in vitro morphologic differentiation regardless of their original morphology.

Basement Membrane↗
PubMed1998

Prolonged hepatic warm ischemia in non-heart-beating donors: protective effects of FK506 and a platelet activating factor antagonist in porcine liver transplantation.

BACKGROUND: Prolonged warm ischemic injury in non-heart-beating donors (NHBDs) significantly affects hepatic allograft function after liver transplantation (LTx). METHODS: The effects of FK506 and the platelet activating factor antagonist E5880 on postoperative function of hepatic allografts procured from NHBDs were evaluated in porcine orthotopic LTx. In donors, livers were subjected to 90 minutes of warm ischemia and a subsequent 4-hour cold preservation. Group 1 (n = 6) was the untreated control group. In group 2 (n = 4), donors were pretreated with FK506 (0.3 mg/kg). In group 3 (n = 4), donors and recipients were treated with E5880 (0.3 mg/kg). In group 4 (n = 6), pigs were treated with both FK506 and E5880. RESULTS: All of the recipients in group 1 died within 12 hours. In groups 2 and 3, half of the recipients survived more than 12 hours. In group 4, all of the recipients survived more than 2 days (p < 0.01 compared with group 1). The improved survival seen in group 4 was associated with a reduction in the serum concentrations of glutamic oxaloacetic transaminase and lactate, and a restoration of hepatic energy charge. CONCLUSIONS: The present study suggests that FK506 and E5880 can improve the function of hepatic allografts subjected to prolonged warm ischemia in NHBDs, and that the protective effects of the two drugs seem to be synergistic.

Adenosine Triphosphate↗
PubMed1998

[Multi-parametric analysis for leukemic immunophenotyping].

We have investigated whether immunophenotyping measured by laser flow cytometry could be corresponding to FAB classification of acute leukemias, using multi-parametric analysis. Sixty-one patients with acute leukemias have been evaluated, including 23 patients with acute lymphocytic leukemias (ALL) and 38 patients with acute myelogenous leukemias. In principal component analysis, positive cell surface antigens could be classified into groups along to the cell lineage and differentiation. In discriminant analysis, the sensitivity by immunophenotypic method to FAB subtypes was 75%, whereas the specificity was over 90%. In cluster analysis, patients have been classified into 4 groups, which essentially corresponded to ALL, M1/M2, M3 and M4/M5. Based on those multi-parametric analysis, a new flow chart has been established, resulting that the sensitivity and the specificity was improved to over 90% and 95% respectively. These results suggest that the classification of acute leukemia using the flow chart could be useful tools for diagnosis of subtypes of acute leukemias.

Antigens, Surface↗
PubMed1997

Sample preparation from paraffin-embedded tissue specimens for laser scanning cytometric DNA analysis.

We have developed a simple, rapid method for isolating cells from a block of formalin-fixed, paraffin-embedded tissue specimen for laser scanning cytometric (LSC) DNA analysis by using a grater. The scraping-like tissue samples were obtained by grating a paraffin-embedded tissue block. The grated samples were collected, put into a small plastic tube, and deparaffinized with xylene. Subsequently, the samples were immersed in 100% ethanol to remove the xylene. After using a syringe with a 26-gauge needle and filtering through 40-microm nylon mesh, the cells suspended in ethanol were dropped directly onto a glass slide. As a result, isolated cells adhered tightly to the glass slide. The slides mounted with isolated cells were treated with 0.1% pepsin in 0.1 N HCl for 1 h at 37 degrees C and then 0.1% RNase for 10 min at room temperature. The slides were dipped in propidium iodide (25 microg/ml) to stain DNA and sealed with nail varnish. The coefficients of variation for histograms were small enough to detect an aneuploid peak close to the diploid peak.

Aneuploidy↗
PubMed1997

Hepatic allograft procurement from non-heart-beating donors: limits of warm ischemia in porcine liver transplantation.

To investigate the tolerance to warm ischemia of liver grafts from non-heart-beating donors, porcine orthotopic liver transplantation was performed using grafts obtained at various periods after cardiac arrest. Graft viability was investigated in relation to changes in hepatic adenine nucleotide metabolism. In donors, livers were divided into four groups according to warm ischemic time after cardiac arrest (group 1: 0 min, n=3; group 2: 30 min, n=3; group 3: 60 min, n=5; group 4: 90 min, n=4). Thereafter, the livers were flushed and preserved for 4 hr using 4 degrees C Euro-Collins solution. After surgery, all of the recipients in groups 1, 2, and 3 survived more than 4 days, except for one pig in group 3 that died of bleeding from an arterial catheter on day 2. By contrast, all of the recipients in group 4 died within 12 hr. The serum glutamic oxaloacetic transaminase concentration at 4 hr after reperfusion of the graft was significantly higher in group 4 (mean+/-SE, 2563+/-556 IU/L) than in groups 1, 2, and 3 (298+/-29 IU/L, 1226+/-222 IU/L, and 1181+/-174 IU/L, respectively). The adenylate energy charge of the liver graft recovered at 1 hr after reperfusion of the graft to 0.852+/-0.013, 0.845+/-0.003, and 0.842+/-0.003 in groups 1, 2, and 3, respectively. The recovery was significantly suppressed in group 4 (0.796+/-0.011). The hepatic adenosine triphosphate concentration also was significantly lower in group 4 compared with the other groups. The present study suggests that liver allografts can be used from non-heart-beating donors subjected to warm ischemia for less than 60 min. Postoperative survival is associated with prompt recovery of the adenylate energy charge of the liver graft.

Adenine Nucleotides↗
PubMed1997

Natural history of a spontaneous dissecting aneurysm of the proximal superior mesenteric artery: report of a case.

We report herein the case of a 44-year-old man in whom an asymptomatic dissecting aneurysm was found in the proximal part of the superior mesenteric artery (SMA) during a preoperative evaluation for colon cancer. The patient was managed conservatively with blood pressure control during the perioperative period of the colon resection as the false lumen of the dissecting aneurysm was revealed to be completely occluded by thrombus. The thrombus in the false lumen continued to be absorbed until 1 month after surgery. The patient is currently well 4 years after his operation without any evidence of recurrence of the aneurysm.

Adenocarcinoma, Papillary↗
PubMed1997

Invasive potentials of gastric carcinoma cell lines: role of alpha 2 and alpha 6 integrins in invasion.

The potentials of the two major histological types of gastric carcinoma to invade through extracellular matrices were studied with cell lines. We found that the invasive potential of intestinal-type carcinoma cells (MKN-28 and MKN-74) were higher than those of diffuse-type carcinoma cells (MKN-45 and KATO-III). To investigate whether the alpha 2 and alpha 6 integrin adhesion molecules are responsible for, or involved in carcinoma invasion. We further studied alpha 2 and alpha 6 expression patterns in these two types of cell line. Although fluorescence-activated cell sorting analysis revealed that all cells examined invariably expressed these integrin molecules, their expressional patterns were different among different cell lines. The intestinal-type carcinoma cells expressed integrins mainly along the cell-cell contact region, whereas the diffuse-type carcinoma cells showed a diffuse cytoplasmic pattern of integrin expression. Invasion by MKN-28, MKN-74 and MKN-45 cells through reconstituted basement membrane or type I collagen gel was significantly inhibited (P < 0.05) by 50 micrograms/ml anti-(alpha 2 integrin) or anti-(alpha 6 integrin) monoclonal antibodies. Our results suggest that active invasiveness is stronger in the intestinal-type than in the diffuse-type carcinoma cells and that alpha 2 and alpha 6 integrins play important roles in invasion of both types of gastric carcinoma cell lines.

Antigens, CD↗
PubMed1997

[Chemotherapy for primary bile duct cancer].

The prognosis for patients with bile duct cancer (BDC) is still dismal, because of the high incidence of postresection recurrence and frequency of unresectable tumors. Chemotherapy has been applied over 20 years with anticipation of enhanced response rate together with minimal adverse effects and prolonged survival. Despite the scarcity of experiences with chemotherapy dedicated to BDC, some efficacy of chemotherapy on BDC has been indicated by this review of the literature. Chiefly, the administered drugs to unresectable BDC were 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin-C (MMC). Systemic chemotherapy, employing those drugs as single agents or as a combination like FAM (5-FU + ADM + MMC), was most commonly administered. The collective response rate was 18.6% (13/70), including a higher response rate of 29% (4/14) by FAM. Regional chemotherapy by hepatic arterial infusion has been expected to be more effective from the view point of blood supply, however, only a few trials have been reported as long as BDC. The series from the literature show a collective response rate of 50% (3/6) for hepatic arterial infusion therapy. The total number of patients (n = 16) treated by intra-ductal chemotherapy is too small to estimate clinical efficacy despite a relatively high collective response rate of 43.8% (7/16). This paper should encourage further investigation of chemotherapy for BDC.

Antineoplastic Agents↗
PubMed1996

[Evaluation of reserved hepatic function in patients with hepatobiliary tumor by 99mTc-GSA: effect of hyperbilirubinemia and usefulness of regional reserved hepatic functional imaging].

The evaluation of the reserved hepatic function was performed by 99mTc-galactosyl serum albumin (99mTc-GSA) in seventy patients with hepatobiliary tumor. The dynamic study was performed to evaluate global reserved hepatic function following the intravenous bolus injection of 99mTc-GSA, and the hepatic single photon emission computed tomography (SPECT) was obtained to assess the regional reserved hepatic function. The functional hepatic index (LHL15) was derived from liver time-activity data, and it was compared with serum total-bilirubin level, serum albumin level and plasma disappearance rate of indocyanine green (ICG15). In the patients with hepatocellular carcinoma, LHL15 value agreed well with ICG15 value, serum total-bilirubin level, and serum albumin level. Moderate or severe hepatic dysfunction was observed at 65.4% of these patients. In the patients with cholangiocellular carcinoma, a discrepancy of LHL15 value and ICG15 value was observed. Increment of the ICG15 value was correlated with that of the serum total-bilirubin level, whereas the correlations was not observed between the LHL15 value and the serum total-bilirubin level. These results indicate that 99mTc-GSA scintigraphy can evaluate the reserved hepatic function without the embellishment of jaundice. This method is useful for assessing the global and regional reserved hepatic function.

Aged↗