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Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Flow cytometric analysis on perforin induction in peripheral blood mononuclear cells with interleukin-2 or OK-432.

Perforin is a protein present in the cytoplasmic granules of killer cells and is considered to be an important effector molecule. We assessed the perforin appearance via flow cytometry in human peripheral blood mononuclear cells stimulated in vitro for 3 days by recombinant interleukin-2 (rIL-2) or OK-432, a biological response modifier. The relationship between the lymphocyte subsets and perforin was investigated via two-color assay. CD4-positive cells had almost no perforin, and most of the CD16-positive cells did. Regarding the relationship with CD8, some of the bright positive cells (which were likely T cells) and most of the dull positive cells (likely NK cells) had perforin. Mean fluorescence was greatest in perforin-positive cells incubated with rIL-2, less in cells incubated with OK-432, and minimal in cells incubated in a medium without additives. Immunohistochemical staining with antiperforin antibody revealed that blast-transformed and enlarge cells were stained positively and that the intensity of staining of each cell alone was enhanced in cells incubated with OK-432 or rIL-2. If the fluorescence intensity of perforin-positive cells correlates with the amount of perforin in those cells, then the appearance of perforin was enhanced with OK-432, more enhanced with rIL-2, and consistent for cytotoxicity against K562 and Daudi cells. IL-2 was induced by OK-432, suggesting that the indirect effect of this IL-2 may play a role in OK-432-perforin induction. The results suggest that perforin may be an effector molecule in killer cells induced by rIL-2 or OK-432.

Cytotoxicity, Immunologic↗
PubMed1992

The changing pattern of the splenic lymphocyte subsets in tumor-bearing mice after oral treatment with OK-432.

The aim of this study was to investigate the influence of oral administration of OK-432 on the tumor growth of tumor-bearing mice. In addition, the changing pattern of the splenic lymphocyte subsets of tumor-bearing mice was evaluated by flow cytometry. OK-432 at a dose of 0.1, 1 or 10 KE was administered orally every 3 days or every other day for 30 days to subcutaneously Meth A tumor-inoculated mice. The tumor growth was significantly inhibited in the 1 KE every 3 days group, in the 1 KE every other day group and in the 10 KE every 3 days group. In the 10 KE every other day group, OK-432 inhibited the tumor growth on days 10 and 20, while the agent did not show a marked inhibitory effect on day 30. The percentages of splenic L3T4-positive cells and splenic asialo GM1-positive cells were significantly increased in the 1 KE every other day group, while the Lyt2+/Thy1.2+ ratio was decreased. On the other hand, in the 10 KE every other day group, OK-432 showed no effect on the percentages of splenic L3T4-positive cells and Lyt2+/Thy1.2+ ratio on days 20 and 30. Our results suggest that the antitumor effect of oral administration of OK-432 may be correlated with the changing pattern of L3T4-positive cells and Lyt2+/Thy1.2+ ratio.

Administration, Oral↗
PubMed1992

Anti-proliferative effect on human pancreatic cancer cells of natural human tumour necrosis factor-beta combined with natural human interferon-alpha or interferon-gamma.

The anti-proliferative effects of natural cytokines, human tumour necrosis factor-beta, natural human interferon-alpha and natural human interferon-gamma, on three human pancreatic cancer cell lines (PANC-1, MIA PaCa-2 and BxPC-3) were investigated in vitro. The anti-proliferative effect was determined using the dye uptake method and analysed for synergism by the median effect principle. Tumour necrosis factor-beta, as a single agent, had little anti-proliferative effect on any of the three cell lines, whereas interferon-alpha and interferon-gamma exhibited a strong anti-proliferative effect against two cell lines (MIA PaCa-2 and BxPC-3) and one cell line (BxPC-3), respectively. When tumour necrosis factor-beta and interferon-alpha were administered together (ratio 1:1), a synergistic effect was observed against PANC-1 cells. The combination of tumour necrosis factor-beta and interferon-gamma (ratio 10:1) was synergistic against both PANC-1 and MIA PaCa-2 cells. A synergistic anti-proliferative effect of tumour necrosis factor-beta and interferons was, therefore, observed even for cell lines that showed little biological response to each cytokine alone. The data suggest that some future improvement in the treatment of pancreatic cancer may be obtained by using combination cytokine therapy.

Cell Division↗
PubMed1992

Inhibitory effect of nafamostat mesilate on metastasis into the livers of mice and on invasion of the extracellular matrix by cancer cells.

Although many agents that interfere with clotting mechanisms have been investigated for their potential to inhibit metastasis, their toxicity has prevented administration of sufficiently high doses to achieve inhibition of metastasis in clinical trials. Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, inhibited liver metastasis in a CDF1 mice model with colon 26 adenocarcinoma cells. The apparently dose-dependent inhibitory effect was seen 21 days after all of the doses tested (0.3, 1.0, 3.0 and 10.0 mg/kg for 7 days) but the effect was only statistically significant (P less than 0.01) at the highest dose. The blood concentrations 3 min after dosing were less than 10(-6) M for all of the doses tested. At a concentration of 10(-5) M or less nafamostat mesilate was not cytotoxic towards colon 26 cells in vitro. The results indicate that it may not be difficult to achieve blood nafamostat mesilate concentrations that inhibit metastasis in mouse liver. Possible mechanisms of nafamostat mesilate are inhibition of extravasation and invasion of cancer cells, inactivation of collagenase due to inhibition of plasmin activity and inhibition of the formation of the cancer cell thrombus, and arrest in the capillaries through inhibition of thrombin activity. These preliminary results suggest that peri-operative administration of nafamostat mesilate may prevent metastasis into the liver after surgery for gastrointestinal malignancies.

Adenocarcinoma↗
PubMed1992

The blood vascular bed of the human pancreas, with special reference to the insulo-acinar portal system. Scanning electron microscopy of corrosion casts.

Microdissection and scanning electron microscopy of corrosion casts showed the structures of the vascular bed of the human pancreas to consist mainly of the capillary plexuses of the exocrine lobules, extralobular ducts and endocrine islets. A considerable number of the exocrine lobules were found to contain one to four marked endocrine islets larger than 30 microns in diameter. These intralobular islets received one or more arterioles (afferent vessels) and emitted conspicuous insulo-acinar portal vessels which continued into the lobular capillaries, suggesting insular control over the functions of the exocrine acini of the pancreas. Direct drainage of the intralobular islets into the veins was never reproduced. Not excluding the possibility that some lobules might contain smaller, unidentifiable islets, there nonetheless were many lobules which directly received arterioles. These lobules are free of control by an islet. Rarely, an islet was located in the interlobular tissue space or along an extralobular duct. Such an extralobular islet issued no portal vessels, and drained into the interlobular or periductal veins. The surface of this type of islet comprised a thin network of fine capillaries. A possibility was suggested that this cortical network might be homologous with the lobular capillaries. No portal route was observed between the islets and extralobular ducts. Few connections were noted between the capillary plexuses of the lobules and ducts.

Adult↗
PubMed1992

Laparoscopic cholecystectomy: report of 42 cases.

Our initial experience with laparoscopic cholecystectomy for cholecystitis and cholelithiasis was reviewed in 42 patients and the data were compared with those of 21 patients who underwent conventional open cholecystectomy previously. Only one patient required conversion to an open operation. Three of the 42 patients had minor complications without death in laparoscopic cholecystectomy. The mean time for the laparoscopic cholecystectomy was 100 +/- 40 min, as compared with 79 +/- 21 min for the open cholecystectomy. The average postoperative hospital stay was 11.4 +/- 7.1 days for the laparoscopic procedure and 35.5 +/- 15.4 days for the conventional procedure. The laparoscopic cholecystectomy offers the patients shortened hospitalization and lower complications and can replace the conventional open cholecystectomy in large degree, at least in the uncomplicated cases.

Adult↗
PubMed1992

Acute superior mesenteric artery syndrome following left hemicolectomy: a case report.

Acute superior mesenteric artery syndrome (SMAS) following a major surgical procedure is extremely rare, and represents an iatrogenic cause of postoperative upper gastrointestinal obstruction. In this report, the first documented case of acute SMAS following a left hemicolectomy is presented in an obese patient. Upper gastrointestinal roentgenographic series and conservative management remain to be the first line diagnostic and therapeutic modalities and were successful in our patient. Up to date no patient with SMAS reported to be obese but apparently obesity per se, can not be considered as an insurance. A postoperative acute SMAS is impossible to predict depending on the previous history, predisposing factors and the physique of the patient. Therefore, the surgeon should be aware of the SMAS and it is his task to secure all the precautions in order to preclude excessive traction on the mesenteric vasculature and vascular compression of the duodenum during surgery. In cases in which SMAS is suspected during extended colonic resections with lymph node dissection, duodenal mobilization seems to be selectively justifiable.

Acute Disease↗
PubMed1992

Antiproliferative effects of suramin on human cancer cells in vitro and in vivo.

The present experiment was undertaken to study what types of human cancers are responsive to the antiproliferative effects of suramin. The human malignant cells used were as follows: cervical cancer (HeLa), mammary cancer (MCF-7), bladder cancer (EJ), hepatoma (HuH-7, PLC/PRF/5), embryonal carcinoma (PA-1), in vitro transformed fibroblasts (KMST-6, SUSM-1, VA-13), five myeloma cell lines (KMM-1, KMS-5, KMS-11, KMS-12, RPMI 8226), Burkitt's lymphoma (Raji), acute promyelocytic leukemia (HL-60), chronic myelocytic leukemia (K562), Epstein-Barr virus nuclear antigen positive lymphoblastoid cells (KMS-9). The cells were treated with 25 to 100 micrograms/ml suramin for 72h. Proliferation of HuH-7 and two human myeloma cells (KMS-11 and KMS-12) was remarkably inhibited, and that of PA-1, PLC/PRF/5, KMST-6, two other myeloma cell lines (KMM-1 and KMS-5), Raji and HL-60, was moderately inhibited. In order to confirm part of the results obtained from in vitro experiments, in vivo experiments were also undertaken. The growth of HuH-7 cells transplanted subcutaneously into nude mice was significantly suppressed by intravenous injection of suramin. We discussed the possibility that certain types of human cancers, the growth of which seemed to be more or less dependent on polypeptide growth factors, might be sensitive to the antiproliferative effects of suramin.

Animals↗
PubMed1992

Early phase II study of interferon-alpha and tumor necrosis factor-alpha combination in patients with advanced cancer.

Synergistic enhancement of anti-tumor effects through the combined use of natural human interferon-alpha (nHuIFN-alpha) and natural human tumor necrosis factor-alpha (nHuTNF-alpha) enabled us to decrease the effective dose of each cytokine and consequently to reduce side effects. One hundred and twenty patients with advanced or recurrent solid cancer were entered in the trial from April 1985 to January 1988, of whom 112 patients were evaluable. A mixture of nHuINF-alpha and nHuTNF-alpha was injected intravenously as the maintenance dose 1 x 10(6)U or more/day for over 8 weeks. There was no response in 40 patients injected with the maintenance dose of 1 x 10(6)U/day, but of 72 patients receiving more than 2 x 10(6)U/day (10 micrograms of nHuIFN-alpha and 3 micrograms of nHuTNF-alpha), 4 had complete responses, 10 had partial responses, and 4 had minor responses. The overall response rate was 12.5% (14/112) and the rate was 19.5% in 72 patients with more than 2 x 10(6)U/day. Positive responses were as follows: hepatoma 3/8), renal cell cancer (4/11), breast cancer (4/17), ovarian cancer (1/2), malignant thymoma (1/1) and liposarcoma (1/1). Serious adverse effects like hypotension, oliguria and severe hepatobiliary toxicity were never experienced. The effective and adequate dose of the mixed preparation was considered 2 to 4 x 10(6)U/day/body.

Adult↗
PubMed1992

Assessment of lymph node metastasis and vessel invasion in early rectal cancer.

Thirteen patients with rectal carcinoma seen between December 1980 and December 1990 have been reviewed to determine the risk of lymph node metastasis and its implication for subsequent treatment. The mean age was 64 years (from 38 to 79; 9 males, 4 females). The site of the tumor was predominantly in the lower rectum (53.8 percent). The polypoid (I) and flat-elevated ulcerated (IIa + IIc) subtypes were detected in seven and six lesions, respectively. Sphincter-saving techniques were carried out in eight cases, and five cases required Miles' operation. Neither postoperative complications nor deaths were noted. The mean follow-up period was 57 months (6 to 133 months). No recurrence or distant metastasis was found during this follow-up. IIa + IIc subtype lesions with deep submucosal invasion at or beyond Smlc level were closely related with lymphatic and vascular invasion. Although this association was not necessarily accompanied by an increased number of involved lymph nodes, major surgical resection is suggested in such IIa + IIc cases due to an increased possibility for lymph node metastasis.

Adult↗
PubMed1992

Laparoscopic cholecystectomy report of 30 cases.

Laparoscopic cholecystectomy (LSC) was attempted in 30 patients and was accomplished in 29 during the nine months between March and November 1991. Twenty eight patients had cholelithiasis with or without adenomyosis, and two had adenomyosis of the gall-bladder. Mean operative time was 219 min and postoperative pain was slight. Two complications (6.9%), including necrosis of the common hepatic duct and subcutaneous emphysema, were encountered. Patients with subacute and severe chronic cholecystitis were included in the cases. Thus this technique is recommended for almost all patients who require the removal of the gall-bladder for benign diseases.

Adolescent↗
PubMed1992

Surgical treatment for hepatocellular carcinoma (HCC) 3 cm or less than 3 cm in diameter.

The efficacy of surgical treatment of small hepatocellular carcinoma (3 cm less in diameter) was studied in 30 patients with solitary tumors. The survival of the patients surviving at least three months after resection was 95% at 1 year, 69% at 2 years, 50% at 3 and 4 years. With regard to the range of resection in cases of partial resection the survival rate was 94% after 1 year, 64% after 2 years, and 47% after 3 and 4 years, while in the case of more than subsegmental resection the 4-year survival rate was 100% and a significant difference was noted. Recurrence was noted after 47% of the partial resections and 25% of the subsegmental or larger resections, and 6 of the 8 recurrent site especially in lesions of less than 2 cm were within the same segmental region. Thus, in the surgical treatment of solitary cancers smaller than 3 cm in size, resection of the segmental resection seems to be preferred whenever the functional reserves of the liver permits.

Carcinoma, Hepatocellular↗
PubMed1992

[Phase III trial of 99mTc-rhenium colloid for lymphoscintigraphy].

A multicenter study was carried out on 191 patients (196 examinations) with lymphatic system disorders to evaluate the efficacy and safety of 99mTc-rhenium Colloid, a tracer for lymphoscintigraphy (TCK-17). Local pain and swelling occurred at the site of injection in 79.6% and 5.1% of patients, respectively, and 2 patients experienced mild fever. The accuracy was calculated on the basis of the results obtained by other diagnostic methods. Lymphoscintigraphy using TCK-17 was sensitive diagnostic procedures, but low specificity. The efficacy was classified into five grades: "Excellent", "Good", "Moderate", "Equivocal", and "Poor". 67.3% of all examination were evaluated as "Excellent" or "Good". This study revealed TCK-17 was a useful radiopharmaceutical for lymphoscintigraphy because of its safety and effectiveness.

Adult↗
PubMed1992

Can cytokines prolong survival in ampullary neuroendocrine carcinomas?

Herein we report the case of an ampullary tumor in a 53-yr-old Japanese woman who presented in March 1988 with abdominal pain, weight loss, and jaundice. A pancreatoduodenectomy was carried out, and 3 months later, she presented with a Virchow's node. She was initially treated with cytokines plus 5-fluorouracil derivative, resulting in a complete remission lasting over a year. However, in July 1990, the Virchow's node reappeared and was surgically excised. Histology revealed a small-cell neuroendocrine carcinoma (SCNC) similar to the prior ampullary tumor, which was confirmed by immunohistochemical studies and electron microscopic examination. The patient was discharged within 1 month, remaining disease-free over a 18-month period following excision. We suggest that the use of cytokines can be effective, and can increase survival in gastrointestinal neuroendocrine tumors.

Ampulla of Vater↗