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Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 163 records · Page 9Linked to original sources

Per-rectal portal scintigraphy with technetium-99m pertechnetate for esophageal varices.

Per-rectal portal scintigraphy is a non-invasive method in which a radioisotope is used for imaging of the portal collaterals. Per-rectal portal scintigraphy with 99m-technetium pertechnetate (99mTcO4-) was performed in 42 subjects to evaluate the portal hemodynamics. Ten healthy controls, 13 cases of liver cirrhosis without esophageal varices, 15 cases of liver cirrhosis with esophageal varices, and 4 cases of portal systemic shunt were included in this study. Moreover, in 4 patients who underwent transabdominal esophageal transection, per-rectal portal scintigraphy was repeated one month postoperatively. Portosystemic shunt index was calculated by the following equation. Shunt Index (%) = (99mTcO4 Counts of Heart/99mTcO4 Counts of Liver and Heart) x 100. The results, expressed as shunt index (SI) were: 8.8 +/- 5.2 in controls, 21.2 +/- 8.0 in cirrhotic patients without esophageal varices, 31.0 +/- 18.5 in cirrhotic patients with esophageal varices, and 49.0 +/- 6.9 in patients with portosystemic shunt. After transabdominal esophageal transection, the shunt indices were decreased in all four cases. Morphological improvements of the esophageal varices were also observed. These results suggest that the shunt index measured by per-rectal portal scintigraphy may be useful for assessment of portal collaterals, especially for patients with esophageal varices.

Adult↗

Laparoscopic cholecystectomy in cirrhotic patients: expanding indications.

Cirrhosis, portal hypertension, and bleeding disorders are being considered as relative or absolute contraindications to laparoscopic cholecystectomy (LC). This report describes four cirrhotic patients with clinical portal hypertension in three and mild to severe bleeding tendency in all. Laparoscopic cholecystectomy was uniformly successful in these patients with no complications. If the surgeon exercises extreme caution in securing hemostasis and does not overlook some details concerning patient management, LC can be efficiently and safely performed in cirrhotic patients. Compared with open cholecystectomy, LC may be even more advantageous concerning the virtual elimination of incision-related complications. Our preliminary experience is encouraging and suggests more liberal use of LC in cirrhosis-portal hypertension-bleeding tendency disease complex.

Aged↗

[Effects of cisplatin, carboplatin, etoposide and human hepatocyte growth factor on the colony formation of four human liver cancer cell lines].

Antitumor activity of cisplatin, carboplatin, etoposide, or human hepatocyte growth factor (hHGF), was compared by examining the colony formation ability of four liver cancer cell lines (PLC/PRF/5 and HuH-7, hepatocellular carcinoma; HuH-6 and HepG2, hepatoblastoma). Antitumor activity was evaluated from the drug concentration causing 50% cell death by a colony assay. PLC/PRF/5 cells were most effectively killed by cisplatin and etoposide, HuH-7 cells by cisplatin and carboplatin, HuH-6 cells by etoposide, and Hep G2 cells by cisplatin. These results indicate that among four liver cancer cell lines, the three were the most sensitive to cisplatin, the two were to etoposide and the only one cell line was to carboplatin. There was no significant relationship between each drug and types of liver cancer. Combined treatment with cisplatin (0.01-1.0 microgram/ml) and etoposide (0.1 microgram/ml) showed synergistic cytotoxic effects on the colony formation of PLC/PRF/5 cells, while combination of carboplatin (0.01-0.1 microgram/ml) and etoposide (0.1 microgram/ml) caused subadditive cytotoxic effects. hHGF stimulated the colony formation of HuH-6 cells, while it inhibited that of Hep G2 cells. The treatment of HuH-6 with cisplatin and hHGF showed a higher cell survival percentage compared with the treatment with cisplatin alone. On the other hand, cell survival of Hep G2 cells was remarkably decreased by the combined treatment with cisplatin and hHGF.

Carboplatin↗

[In vivo comparative study of the pharmacokinetics of chemotherapeutic agents infused via hepatic artery or portal vein against hepatic metastases. DRC Group].

Recently, the treatment for hepatic metastasis has been performed by injection of chemotherapeutic agents via hepatic artery. Although this therapeutic procedure has been contributing to a relatively higher response rate, the resulting increased response has not significantly improved prognosis. So, we assessed the infusion of chemotherapeutic agents via portal vein in rabbits and compared the results with those from arterial infusion. Two weeks after inoculation of VX-2 tumor cells into the liver, subcapsularly, injection of chemotherapeutic agents as well as sampling of the livers was started. The rabbits were allocated into two groups, an arterial infusion group and a portal vein infusion group. They received a single shot of mitomycin C (MMC, 1.7 mg/kg), or 5-fluorouracil (5-FU, 9.5 mg/kg) or cisplatin (CDDP, 1.6 mg/kg) injected by infusion pump for 1 h. The drug concentration into the normal liver and intratumorally was measured by HPLC method for 5-FU and MMC, and by flameless atomic absorption spectrometry for CDDP. Either drug concentration in the liver or tumor did not substantially differ between the two groups. This experiment revealed that portal vein infusion can contribute as much drug concentration intratumorally as by arterial infusion.

Animals↗

[Analysis of MDR1 (multidrug resistance) gene expression by RT-PCR].

Multidrug resistance to anticancer drugs proved to be related to the MDR1 gene which encodes the P-glycoprotein, an energy-dependent drug-efflux pump for lipophilic drugs. We investigated the expression of the MDR1 gene in clinical samples by RT-PCR. The subjects were all resected cases of 14 colorectal cancers, five gastric cancers, two esophageal cancers, two gallbladder cancers and 20 lung cancers. Adrenal gland was used as a positive control. Total RNA was extracted from a fresh tissue sample. The cDNA was synthesized from 1 microgram of total RNA using reverse transcriptase. With the above cDNA as the template, amplification of the 157-bp fragment of the MDR1 gene was performed using PCR. The PCR product was polyacrylamide gel-electrophoresed and ethidium bromide-stained. In addition, a dot blot analysis was performed to quantify the amount of PCR product. Since PCR was performed simultaneously under the same conditions, the PCR product was quantified at four stages, from (3+) to (-), to indicate the degree of expression of MDR1 mRNA. Adrenal gland showed (3+)-(2+) and colorectal cancer exhibited mostly (2+)-(1+). Both cancerous and non-cancerous areas evidenced a similar degree of expression in the cases of colorectal cancer. The MDR1 gene was expressed at low levels in other digestive tract cancers and in lung cancer. The levels of MDR1 expression revealed no correlation to either histological type or clinical stage. The present method may contribute to designing anti-cancer protocols.

Antineoplastic Agents↗

The significance of post-hepatectomy changes in polymorphonuclear elastase and endotoxin levels.

We studied the association between polymorphonuclear elastase and endotoxin levels and complications following hepatectomy. The blood concentrations of polymorphonuclear elastase, endotoxin, fibrinogen and C-reactive protein were examined with the aim of clarifying their involvement in postoperative complications in twenty-five patients who underwent hepatectomy. Polymorphonuclear elastase increased significantly (p < 0.01) on the second postoperative day compared with preoperative levels, and decreased on the seventh postoperative day. The difference in the polymorphonuclear elastase level with and without liver cirrhosis was significant (p < 0.05) on the second postoperative day. Endotoxin changed in a manner similar to polymorphonuclear elastase, but no positive correlation was found between endotoxin and polymorphonuclear elastase. Neither parameter showed any significant positive correlation with the volume of hepatic resection. We were unable to find any relationship between the degree of elevation of endotoxin and complication after hepatectomy; further study will be needed.

Endotoxins↗

[The inhibitory effect of nafamostat mesilate (FUT-175) on liver metastasis].

Basic investigation of inhibitory effect on metastasis of nafamostat mesilate (FUT-175) which is a kind of serine protease inhibitors, was performed. Colon 26 cells were injected to the portal vein of CDF1 mice. FUT-175 at doses of 0.3, 1.0, 3.0, 10.0 mg/kg was injected intravenously every 7 day. Mice were sacrificed on day 21, and metastasis of liver surface were measured. The dose dependent reduction of metastasis was observed and reduction of metastasis of mice treated at a dose of 10.0 mg/kg was significant. FUT-175 showed no cytotoxicity at doses of 10(-5) M or less in vitro, and blood concentration of mice, treated at a dose of 10.0 mg/kg, was 2.67 x 10(-7) M. The results showed that inhibitory effect of FUT-175 on metastasis was not caused by direct cytotoxicity. FUT-175 at 2.67 x 10(-7) M in vitro can inhibit only thrombin and plasmin at nearly 50%, and can not inhibit platelet aggregation and collagenase directly. Possible mechanism of inhibition of metastasis is that FUT-175 inhibited both thrombin-mediated platelet aggregation and plasmin-mediated collagenase activation, that arrest and extravasation in cancer cells were inhibited. If protease inhibitor is administered continuously and immediately after surgery, liver metastasis may be prevented.

Animals↗

[A case report of tracheal inflammatory pseudotumor].

The tracheal tumor is uncommon, and tracheal inflammatory pseudotumor seems to be rare with only four cases reported in the Japanese literature. We here in report a case of tracheal inflammatory pseudotumor in a 61-year-old Japanese man presenting with dyspnea and wheezing 2 weeks after a sub total gastrectomy Billroth I for gastric cancer in april 1991. At bronchofiberscopic examination a rounded tracheal mass 40 mm distal to the vocal cord was found. High vascular on the surface and obstruction of about 90% of the tracheal lumen was noticed. Surgery was attempted immediately and 25 mm of the trachea was excised. The histopathological findings revealed an inflammatory pseudotumor. We concluded that the tumor was caused by injury during tracheal intubation.

Granuloma, Plasma Cell↗

Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-Year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization.

BACKGROUND: A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day of operation. METHODS: A total of 967 patients were entered and randomized by stratification based on ER status and staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914 (94.5%) were evaluable. At 5-year follow-up, significant prolonged overall survival (OS) and relapse-free survival (RFS) times were seen with the addition of TAM in patients with ER-positive and Stage IIIA T3N0 cancer (1987 UICC-American Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with ER-positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in patients with ER-negative disease. RESULTS: Results of subset analyses suggested a benefit from TAM in postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with node-negative, ER-negative, and Stage IIA T2N1 cancer. CONCLUSIONS: The 5-year results of the current trial showed a survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer.

Adjuvants, Immunologic↗

Outcome in patients with early colorectal carcinoma.

Twenty-four patients seen between 1978 and 1990 with early colorectal carcinoma were reviewed to determine the outcome of surgical treatment. The mean age was 62 (range 35-79) years; there were 16 men and eight women. The site of the tumour was the ascending colon in two patients, sigmoid colon in ten and rectum in 12. The polypoid and flat-elevated ulcerated (IIa+IIc) subtypes were detected in 14 and nine lesions respectively. Restorative colectomy was carried out in 19 patients, and five required Mile's operation. There were no postoperative complications or deaths at a mean follow-up of 71 (range 12-151) months. Neither recurrence nor distant metastasis was found during follow-up. There was a close relationship between the depth of submucosal invasion and presence of flat-elevated ulcerated subtype lesions with lymphatic infiltration. This association may play an important role in the mechanism of metastasis. Major surgical resection is probably required if longer disease-free intervals and better cure rates are desired.

Adult↗

A newly developed hydroxyl radical scavenger, EPC-K1 can improve the survival of swine warm ischemia-damaged transplanted liver grafts.

Using a swine orthotopic liver transplantation (SOLTx) model, we assessed the effect of a new hydroxyl radical scavenger EPC-K1 on warm ischemic damage of the liver graft and recipient survival. Animals were divided into 5 groups. The first group (control group 1) consisted of 5 pigs which were not operated on but served as controls for the indocianine green disappearance rate (K-ICG) determinations. In the second group (control group 2), 10 livers were transplanted without warm ischemia (WI) and the K-ICG values were measured. The third group (control group 3) was the main control group for the study groups and consisted of 5 liver transplants with 30 min of WI without any special treatment. The fourth and fifth groups served as study groups 1 and 2. Five transplants were carried out in each group, as in control group 3. In study group 1 recipients were treated with an additional 5 mg/kg i.v. EPC-K1 and in study group 2 with 20 mg/kg i.v. EPC-K1. Significant improvement in glutamic oxaloacetic transaminase (GOT) and lactate dehydrogenase (LDH) levels, K-ICG values and histological findings were observed in the EPC-K1 treated groups. The intravenous administration of this agent had a strong protective effect on warm ischemic damage after 30 min of WI and could significantly prolong the graft and recipient survival.

Animals↗

Abdominal organ cluster transplantation in pigs and FK506.

Using a swine abdominal organ cluster transplantation model, we investigated the postoperative function and immunological reactions of a cluster graft and evaluated the immunosuppressive activity of FK506. The animals were divided into two groups. Group I (n = 6) served as controls, while in group II (n = 6) a daily dose of 0.1 mg/kg FK506 was given intramuscularly. Postoperative pancreatitis was the most important factor influencing the early outcome in both groups. In group I, the cause of late death was cachexia due to diabetes mellitus induced by pancreatic rejection. In group II, emaciation despite a well-functioning graft was the principal cause of late death. Histologically, in group I the grade of rejection in the pancreas was more severe than in the liver, and no sign of rejection was observed in group II. In conclusion, the pancreas suffered more severe rejection than the liver, and FK506 could significantly prevent cluster allograft rejection in this model.

Animals↗

Ex vivo perfusion of canine pancreaticoduodenal allografts using class-II-specific monoclonal antibody delays the onset of acute rejection.

In the following study, we investigated whether ex vivo perfusion of canine pancreaticoduodenal allografts prior to transplantation using a class-II-specific monoclonal antibody (MoAb) OKIa1) could prevent acute rejection. Untreated grafts were rejected within 6 days after transplantation, and all of these recipients suffered severe hyperglycemia. In contrast, in recipients who received grafts which underwent ex vivo class-II-specific MoAb perfusion treatment, the mean urinary amylase levels were sustained significantly higher (11,733 +/- 4493 vs. 3274 +/- 2108 U/L on day 7, P < 0.005), and mean fasting blood glucose (FBG) levels remained within the normal range (13.4 +/- 5.8 vs. 23.4 +/- 3.9 mM on day 7, P < 0.0005). Low doses of cyclosporin A (CsA) were necessary in order to maintain lower FBG levels. Histopathology analysis on day 7 after transplantation showed that endotheliitis and necrosis were much less prominent in the MoAb-treated grafts. In the light of our results, we conclude that ex vivo perfusion of canine pancreaticoduodenal allografts using a class-II-specific MoAb is effective in delaying the onset of acute rejection, and low doses of CsA could extend this effect.

Animals↗

Analysis of suppressor T cells induced by donor-specific transfusion (DST): establishment of a human T cell hybridoma producing an antigen-nonspecific suppressor factor.

Formation of suppressor T cells (Ts) induced by donor-specific transfusion (DST) is one of the most commonly suggested mechanisms for the beneficial effect of DST. In this study, we established a human T cell hybridoma derived from the peripheral blood lymphocytes (PBL) of a DST-treated patient, which produced an antigen-nonspecific suppressor factor. Post-DST PBL were fused with an azaguanine-resistant mutant of a human T cell leukemia cell line, CCRF-CEM(AG). After selection and cloning, we established one clone producing the mixed lymphocyte reaction (MLR) inhibitory factor (C524: 18%-43% suppression). Suppressive activity of the supernatant obtained from C524 after activation by PHA was highly augmented (64%-88% MLR suppression). This factor inhibited MLR dose-dependently in an antigen-nonspecific and HLA non-restricted manner. These results indicated that Ts clones could be generated in patients receiving DST and that the immunoregulatory factors produced by activated clones may play a role in the prolongation of renal allograft survival.

Antibody Specificity↗