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Biomedical subjects

S Takao

Publications and source records attributed to S Takao.

At least 55 records · Page 3Linked to original sources

Length and quality of survival following external beam radiotherapy combined with expandable metallic stent for unresectable hilar cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: Hilar cholangiocarcinoma is a morbid disease with a poor prognosis because resection cannot be performed in many cases. The purpose of this study was to evaluate whether external beam radiotherapy (RT) combined with expandable metallic biliary stent (EMS) affects the length and quality of survival of patients with unresectable hilar cholangiocarcinomas. METHODS: Fifty-one patients with unresectable hilar cholangiocarcinoma were retrospectively reviewed. Thirty patients received external beam radiotherapy combined with EMS (EMS+RT group), 10 patients were treated with EMS alone (EMS group), and the remaining 11 patients underwent percutaneous transhepatic biliary drainage alone (PTBD group). The length and quality of survival were analyzed and compared among the three groups. RESULTS: The mean survival of 6.4 months in the EMS group was significantly longer than that of 4.4 months in the PTBD group (P < 0.05). The EMS+RT group with a mean survival of 10.6 months had a significantly longer survival than the EMS group (P < 0.05). The average of the monthly Karnofsky scores of 74.9 in the EMS+RT group and 68.1 in the EMS group, as a parameter of quality of survival, was significantly higher than that of 57.7 in the PTBD group (P < 0.01). The number of hospital days per month of survival was significantly smaller in the EMS+RT and EMS groups than in the PTBD group (10.4, 14.2 vs. 27.3 days; P < 0.001). The EMS+RT group had a longer stent patency than the EMS group (mean: 9.8 vs. 3.7 months; P < 0.001). CONCLUSIONS: These results indicate that external radiotherapy combined with metallic biliary endoprosthesis can increase the length and quality of survival and consequently provide a definite palliative benefit for patients with unresectable hilar cholangiocarcinoma.

Adult↗

Biological evaluation of undifferentiated carcinoma of the esophagus.

BACKGROUND: Patients with undifferentiated carcinoma of the esophagus (UEC) are rare and have a poor prognosis compared with those with differentiated squamous cell carcinomas (DECs). We compared clinicopathological and biological features of UEC and DEC, with emphasis on markers for epithelial cell origin, proliferation, and cell-cell adhesion. METHODS: Seven patients with UEC were compared with 21 with DEC. Immunohistochemical studies were performed by using monoclonal antibodies to cytokeratin, epithelial membrane antigen, p53, p21WAF1/CIP1, Ki-67, E-cadherin, desmoglein-1, and thrombomodulin. RESULTS: Patients with UEC had a poorer prognosis because of hematogenous metastasis at the time of presentation (mean survival, 6.5 +/- 6.2 vs. 35.5 +/- 28.9 months; P < .05). Immunohistochemical findings for cytokeratin and epithelial membrane antigen suggest that some UECs had epithelial origins. The following immunohistochemical profile of UEC was consistent with its highly malignant properties: (1) reduced or negative expression of cell-cell adhesion molecules such as E-cadherin, desmoglein-1, and thrombomodulin, (2) high positive rate for p53 and Ki-67, and (3) negative expression of p21WAF1/CIP1. CONCLUSIONS: The immunohistochemical findings for UEC showed its high cell-proliferative activity and a high potential for metastasis. Clinical features of UEC were supported by the results of immunohistochemical findings.

Adult↗

Gastric acidity following pancreaticogastrostomy with pylorus-preserving pancreaticoduodenectomy.

Pancreaticogastrostomy (PG) has been reintroduced and employed occasionally as a useful alternative to pancreaticojejunostomy (PJ) after Whipple resection or pylorus-preserving pancreaticoduodenectomy (PPPD). Although the physiologic alteration in the stomach is important for the correlation between gastric and pancreatic functions, the actual intragastric pH profile after PG is still unclear. This study was conducted to investigate the physiologic changes in gastric pH and serum gastrin and secretin levels before and after PPPD reconstructed with PG (PPPD-PG) in humans. Twenty-four hour continuous intragastric pH and serum gastrin and secretin levels in the fasting state were examined in 25 patients who had undergone PPPD-PG. No peptic ulcer was detected after the operation. After PG, serum gastrin and secretin levels were unchanged. Twenty-four hour gastric pH monitoring revealed two distinct patterns during the nocturnal period before the operation: patients with acid-type secretion (n = 11) exhibited a persistent acid pH, whereas those with alkaline-type secretion (n = 14) had cyclic variations between an acid and an alkaline pH value. After PG, in both acid- and alkaline-type patients, median pH and percentages of time that the gastric pH was less than 4 (% pH < 4) and more than 6 (% pH > 6) did not change, and circadian pH patterns also remained unchanged. These results suggest that PPPD-PG has little influence on gastric acidity, and the neurohumoral relation between the stomach, duodenum, and pancreas is preserved after PG. Therefore, physiologically, PG can be recommended as a reconstructive procedure after PPPD.

Adult↗

Ultrasonically activated scalpel is an effective tool for cutting the pancreas in biliary-pancreatic surgery: experimental and clinical studies.

The ultrasonically activated scalpel, a new tool for cutting and coagulating tissue, uses high-frequency ultrasonic vibrations, and has been widely employed in the field of laparoscopic surgery. We evaluated its usefulness for cutting the pancreas in biliary-pancreatic surgery. We planned experimental and clinical studies using an ultrasonically activated scalpel (harmonic scalpel) for cutting the pancreas. The harmonic scalpel was set up at a power level of 3 (75% of full power) in the knife mode. In the experimental study, using dogs, cutting of the pancreas with the harmonic scalpel resulted in significantly less bleeding and significantly less histological tissue damage to the cut stumps than cutting of the pancreas with an electric or a regular scalpel. In the clinical study: (1) the hemostatic effect of the harmonic scalpel was excellent or good in any condition of the pancreas; (2) of 50 stumps of the main pancreatic duct cut with the harmonic scalpel, the stump was easily found in 48 (96%), while ultrasonography was necessary to find the remaining 2 stumps in soft pancreas; (3) in 41 anastomoses (29 soft and 12 hard pancreas) there were no postoperative pancreatic fistulae. These results indicate that the ultrasonically activated scalpel is an effective tool for cutting the pancreas in biliary-pancreatic surgery.

Animals↗

Spindle cell carcinoma of the pancreas.

We experienced a rare case of spindle cell carcinoma of the pancreas. The patient was a 74-year-old man who complained of abdominal pain and loss of weight. Ultrasonographic scans revealed a hypoechoic solid mass in the head of the pancreas, 4 cm in diameter, with a high echoic spot suggestive of central necrosis or hemorrhage. The mass was hypodense on enhanced computed tomographic scans and hypovascular on angiograms. At laparotomy, the tumor had invaded to the mesocolon, but dissemination and distant metastasis were not found. We therefore performed pylorus-preserving pancreatoduodenectomy and ascending colectomy. The patient was discharged on postoperative day 26 after an uneventful recovery. Two months later, he was readmitted because of ascites, with positivity of spindle cells shown on cytology; he died on day 92 after surgery. In the resected specimen, the tumor had a mostly sarcomatous component, consisting of spindle-shaped cells, and a small glandular component. Immunohistochemically, both components were positive for cytokeratin and epithelial membrane antigen, but negative for vimentin and desmin. The tumor was diagnosed as a spindle cell carcinoma of the pancreas. Perineural invasion, lymphatic permeation, and blood vessel invasion were found, but lymph node metastasis was not found. Although a curative operation was performed, the outcome in this patient was very poor.

Aged↗

Seroprevalence of human T-lymphotropic virus type 1 in Papua New Guinea and Irian Jaya measured using different western blot criteria.

BACKGROUND: Endemic foci of HTLV-1 carriers have been found in the world, however, the origin of HTLV-1 in humans is still unclear. Since a distinct type of virus strain was isolated from the Solomon Islands, detailed surveys on HTLV-1 prevalence in New Guinea are important to shed light on its history of dissemination. OBJECTIVE: To clarify the seroprevalence of HTLV-1 in different regions of New Guinea Island. STUDY DESIGN: Sera from 1221 individuals (649 males, 454 females and 118 unknown) in New Guinea Island were studied for the presence of antibodies to HTLV-1 by a particle agglutination and the Western blot (WB) tests. Two different sets of criteria, proposed by WHO and Kiyokawa et al., were employed to interpret the WB test. Since the latter seemed to lack adequate specificity, the WHO criteria was used for the evaluation of the seroprevalence throughout the study. RESULTS: Seroprevalence of HTLV-1 differed by the WB criteria. By the more stringent criteria, HTLV-1 carriers were found in Madang, Chimbu and one hinterland province, Enga, in Papua New Guinea. An overall seroprevalence rate in different regions ranged from 0 to 14.6%. No seropositive individuals were found in Irian Jaya. CONCLUSIONS: To avoid overestimating the seropositivity rates, the WHO criteria would be more appropriate to employ for WB test by using the samples obtained from tropical and/or malaria endemic areas. This study is the first to show HTLV-1 infected individuals in the hinterland of New Guinea Island.

Adolescent↗

Endothelial cells potentiate phagocytic killing by macrophages via platelet-activating factor release.

The immunomodulatory function of endothelial cells (EC) includes the initiation of leukocyte margination, diapedesis, and activation through the upregulation of various cell surface-associated molecules. However, the effect that EC have on the phagocytic function of neighboring monocytes and macrophages is less well described. To address this issue, microvascular EC were cocultured with murine peritoneal macrophages, first in direct contact, then in a noncontact coculture system, and macrophage phagocytosis and phagocytic killing were assessed. The presence of increasing concentrations of EC resulted in a dose-dependent increase in macrophage phagocytic killing. This stimulatory effect was inhibited in a dose-dependent manner by the pretreatment of macrophage/EC cocultures with WEB-2086 or CV-6209, specific platelet-activating factor (PAF)-receptor antagonists, but not by anti-tumor necrosis factor-alpha, anti-interleukin (IL)-1alpha, or anti-IL-1beta. Furthermore, the effect was reproduced in the absence of EC by the exogenous administration of nanomolar concentrations of PAF. Microvascular EC potentiate macrophage phagocytic killing via the release of a soluble signal; PAF appears to be an important component of that signal.

Animals↗

Detection and clinical significance of lymph node micrometastasis determined by reverse transcription-polymerase chain reaction in patients with esophageal carcinoma.

We investigated micrometastasis in lymph nodes by detecting carcinoembryonic antigen (CEA) mRNA. A total of 400 lymph nodes obtained from 21 patients with esophageal carcinoma were examined by CEA-specific reverse transcription-polymerase chain reaction (RT-PCR). Serial sections of positive lymph nodes were reexamined histologically and immunohistologically. Twenty-seven lymph nodes of 11 patients were diagnosed as being positive by conventional histologic examination. CEA-mRNA positivity was found in 18 of 21 patients. Among 373 histologically negative nodes, 79 (21.2%) were positive for CEA mRNA. Of these, micrometastasis was detected in 2 by histological reexamination and in 11 by immunohistochemical staining using cytokeratin antibody. Two of 6 RT-PCR-positive patients (33.3%) had recurrent disease. Four of 11 patients (36.4%) whose nodal involvement was discovered by routine histological examination also had recurrent cancer. CEA-specific RT-PCR detected micrometastasis in lymph nodes at a higher rate than histological or immunohistochemical analysis of serial sections. Since the incidence of CEA-mRNA positivity is high in the lymph nodes of esophageal cancer patients except for those with early cancer, these patients should be treated with adjuvant therapy.

Carcinoembryonic Antigen↗

Down-regulation of E-cadherin by antisense oligonucleotide enhances basement membrane invasion of pancreatic carcinoma cells.

Pancreatic carcinoma shows a marked invasiveness around tissues lymph node and/or hematogenous metastases resulting in poor prognoses of the patients. We examined on whether E-cadherin is associated with these malignant behaviors of pancreatic carcinoma cells using a human pancreatic adenocarcinoma cell line, JHP-1. Immunohistochemically, E-cadherin expression of JHP-1 cells was remarkably inhibited by treatment with E-cadherin antisense oligonucleotide. By invasion-MTT assay, JHP-1 cells treated with E-cadherin antisense oligonucleotide showed a significant increase of invasiveness compared to those treated with the control oligonucleotide (P < 0.001), whereas the proliferation of JHP-1 cells was not affected by the presence of either E-cadherin antisense or control oligonucleotide. Thus, down-regulation of E-cadherin of pancreatic carcinoma cells induced the invasiveness into the basement membrane. These results suggest that the reduction in E-cadherin expression plays a key role not only in detachment of cell-cell adhesion but also in invasion and metastasis of pancreatic carcinoma cells.

Adenocarcinoma↗

[A noteworthy case of postoperative liver metastasis from gastric cancer which responded well to UFT therapy].

A 66-year-old male underwent partial gastrectomy (resection of the pyloric side of the stomach) at another hospital on the basis of a diagnosis of gastric cancer (Fig. 1). Five months later, his CEA level began to rise. At that time, multiple liver metastases were detected by ultrasonography and CT scans. The patient received oral UFT therapy (400 mg/day) at our hospital. A reduction in CEA was observed 63 days after the start of this therapy. A judgment of CR (complete response) was made after 4 months of the therapy. At present, 2 years and 4 months after UFT was first administered, the patient shows no signs of tumor recurrence. This case is noteworthy since there has been no previous report of a case where UFT showed a high efficacy in treating liver metastasis after surgical resection of gastric cancer.

Adenocarcinoma↗

Sensitivity of human pancreatic adenocarcinoma tumor lines to chemotherapy, radiotherapy, and hyperthermia.

BACKGROUND: Surgical treatment of pancreatic adenocarcinoma has failed to produce many cures secondary to high rates of intraperitoneal relapses and liver metastases. The aim of this ex vivo study was to evaluate the inherent chemosensitivity, radiosensitivity and hyperthermic sensitivity of pancreatic adenocarcinoma and to investigate the usefulness of a 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay utilized in each sensitivity test. METHODS: Nine human pancreatic adenocarcinomas were tested ex vivo after growth in nude mice. After 72 hr of chemotherapy, radiotherapy and hyperthermia, efficacy was assessed using MTT assay to determine the ratio of surviving fraction of treated cells-to-that of untreated control cells (TIC ratio). RESULTS: Tumor sensitivities as measured by the IC50 (drug concentration producing 50% growth inhibition) varied largely between drugs, ranging larger than 3 x 10(5) ng/mL for 5-FU, larger than 1.5 x 10(2) ng/mL for MMC, 20 ng/mL to 1.4 x 10(3) ng/mL for ADM, and 80 ng/mL to 2.4 x 10(3) ng/mL for CDDP. D0 (dose of radiation reducing the surviving fraction to 37%) ranged from 3.2 to 8.3 Gy (mean +/- standard deviation; 5.8 +/- 1.6 Gy). For hyperthermia, the mean T50 (duration of hyperthermia reducing the surviving fraction to 50%) at 43 degrees C was 9.4 +/- 3.3 min 4.8 to 14.2 min). The T/C ratio at 43 degrees C for 12 min was less than that at 41 degrees C for 30 min (p = .01; the Wilcoxon signed-ranks test). No clear relationship among chemosensitivity, radiosensitivity, hyperthermic sensitivity and pathologic features could be established. CONCLUSIONS: Nine human pancreatic adenocarcinomas varied widely in their sensitivity to chemotherapies, especially for 5-FU. These results suggested that MTT assay may be useful in excluding some less sensitive cases of pancreatic cancer. For hyperthermia, sufficient therapeutic time and temperature may realize enough effect against pancreatic adenocarcinoma.

Adenocarcinoma↗

N-acetyl cysteine inhibits cell cycle progression in pancreatic carcinoma cells.

The antioxidant N-acetyl cysteine (NAC) is a precursor of intracellular glutathione (GSH) and is also a well known as one of the chemopreventive agents which act through a variety of cellular mechanisms. We examined the effects of NAC on cell cycle progression in the pancreatic carcinoma cell lines, SW1990 and JHP1. Cells were incubated with or without NAC. Cell cycle distribution was analyzed by flow cytometry and immunoblotting. NAC suppressed cell proliferation in a concentration-dependent manner, whereas NAC increased intracellular glutathione content significantly in a dose-dependent manner. The percentage of cells in the G1 phase after treatment with NAC was significantly higher than the percentage seen for control cells. Cyclin D1 expression of carcinoma cells treated with NAC decreased remarkably compared with cells without NAC treatment. Thus, the antiproliferative effect of NAC by prolongation of the G1 phase in human pancreatic carcinoma cells shows its possible utility as an antitumor agent.

Acetylcysteine↗

Human T-lymphotropic retrovirus type-1 in Thailand.

Seroprevalence of antibodies to human T-lymphotropic virus type-1 (HTLV-1) was surveyed among the Thai population by the particle agglutination test and Western blotting test. None of a total of 727 individuals from seven ethnic groups were positive for the specific antibody to HTLV-1. Among hospital based 3,427 subjects in Southern Thailand, one patient with a brain tumor showed positivity in the Western blotting test, however, HTLV-1 proviral genome was not identified by PCR. The present data suggest that HTLV-1 is not endemic in the Thai population and that HTLV-1 is not a major public health problem in Thailand because HTLV-1 rarely causes its associated diseases.

Antibodies, Viral↗

Mucin core protein expression in extrahepatic bile duct carcinoma is associated with metastases to the liver and poor prognosis.

BACKGROUND: Curative resection does not guarantee long term survival for the patient with extrahepatic bile duct carcinoma because of the possibility of metastases to the liver (LM). Expression of mucin core protein-1 (MUC1), sialyl-Le(x), and sialosyl-Tn in bile duct carcinoma was determined and compared with LM and prognosis. METHODS: Immunohistochemical expression of MUC1, sialyl-Le(x), and sialosyl-Tn in 73 extrahepatic bile duct tumors was analyzed using the DF3, FH6, and TKH2 monoclonal antibodies, respectively. Scoring was based on the percentage of immunoreactive cells: negative, low expression (</=25% immunoreactive cells), and high expression (>25%). RESULTS: High expression of MUC1, sialyl-Le(x), and sialosyl-Tn was observed in 68.5%, 34.2%, and 54.8%, respectively. of 73 cases. Patients with tumors showing high expression of MUC1 had a higher rate of LM (48.9%) and a significantly shorter survival period (median survival time, 17.8 months) compared with patients with tumors showing low (incidence of LM, 9.1%; median survival time, >100 months) or negative (incidence of LM, 11.1%; median survival time, 52.9 months) expression of MUC1 (P < 0.01). However, the survival period of patients with tumors showing high, low, or negative expression of sialyl-Le(x) or of sialosyl-Tn did not differ significantly. High MUC1 expression correlated with LM by logistic regression analysis and emerged as an independent prognostic factor in stepwise multivariate analysis. CONCLUSIONS: The results of the current study demonstrate that high expression of MUC1 correlates with LM and poor outcome in patients with extrahepatic bile duct carcinoma.

Adult↗