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Biomedical subjects

K Okuno

Publications and source records attributed to K Okuno.

At least 55 records · Page 3Linked to original sources
PubMed1997

Does lateral lymph node dissection improve survival in rectal carcinoma? Examination of node metastases by the clearing method.

BACKGROUND: The treatment of rectal carcinoma by lateral lymph node dissection has risks and benefits. Therefore, we investigated the therapeutic efficacy of lateral lymph node dissection. STUDY DESIGN: We studied 198 patients with rectal carcinoma who underwent lateral lymph node dissection. Metastases to the lymph nodes were examined by the clearing method. The incidence of urinary and male sexual dysfunction was determined by measuring the residual urine volume and individual interview 1 year after operation. RESULTS: The rate of metastasis to lateral lymph nodes was 11.1 percent, and metastasis to the lateral lymph nodes occurred more frequently with lower rectal carcinoma classified as pT3 or pT4 in the TNM system. The rate of local recurrence was 12.5 percent and the 5-year survival rate after curative resection was 70.1 percent. The 5-year survival rate in patients with metastasis to the lateral lymph nodes was 25.1 percent, and this rate was significantly lower than the 5-year survival rate of 74.3 percent in patients without metastasis to the lateral lymph nodes. Urinary dysfunction was observed in 67.5 percent of patients, and male sexual dysfunction was found in 97.4 percent of men younger than 60 years of age with prior sexual ability. CONCLUSIONS: The prognosis for patients with metastasis to the lateral lymph nodes is poor, and the improvement in survival rate from lateral lymph node dissection is minimal.

Female↗
PubMed1997

Lymph node metastases detected in the mesorectum distal to carcinoma of the rectum by the clearing method: justification of total mesorectal excision.

BACKGROUND: Total mesorectal excision effectively reduces the local recurrence rate of carcinoma of the rectum. This study was undertaken to clarify the rationale for total mesorectal excision. STUDY DESIGN: We retrospectively reviewed the records of 198 patients who underwent resection of a carcinoma of the rectum. The presence of nodal metastases in the mesorectum distal to the primary tumor was examined by the clearing method. RESULTS: The metastatic rate in the distal mesorectum was 20.2 percent. The metastatic rates according to the extent and site of the tumor were as follows: pT1, 0 percent; pT2, 0 percent; pT3, 21.9 percent; pT4, 50 percent; rectosigmoid, 10 percent; upper rectum, 26.3 percent; and lower rectum, 19.2 percent. The longest distal spread from the primary tumor to the metastatic node was 2 cm in carcinoma of the rectosigmoid, 4 cm in carcinoma of the upper rectum, and 3 cm in carcinoma of the lower rectum. CONCLUSIONS: Total mesorectal excision is required for patients with T3 and T4 tumors in the lower rectum, and excision of all mesorectal tissue down to at least 5 cm below the tumor is required for patients with T3 and T4 tumors in the upper rectum.

Humans↗
PubMed1997

Rice genetic resources: history, conservation, investigative characterization and use in Japan.

Rice has been grown in Japan for about 3000 years. Although both japonica and indica varieties have been grown in Japan, now japonica rices are grown. Japanese rice breeding has used an ecological breeding approach. While emphasis in rice breeding in the 1940's and 1950's focussed on yield in recent decades quality has been of major importance. Consumer preference and name recognition of high quality varieties, such as Koshihikari, has resulted in slow acceptance of new varieties. Rice germplasm was systematically collected throughout Japan between 1962 and 1963. Subsequent acquisition and collecting, in Japan and other countries, has resulted in 28,000 accessions being conserved in the National Genebank, based at the National institute of Agrobiological Resources (NIAR). Research on genetic diversity of rice using a range of techniques, for example esterase isozymes, has revealed clinal variation in rice radiating from the center of diversity of rice in and around southwest China. Newly found genes in traditional rice germplasm, such as genes for non-elongating mesocotyl, are now routinely identified on the rice genome. Pioneering studies on eco-genetic differentiation of species in the genus Oryza in Japan has revealed much about the complex genepool for which rice evolved. Pest and disease resistance sources, particularly to blast, bacterial blight and brown plant hopper, from many countries have been incorporated into Japanese varieties. Cold tolerance at the booting stage was found in the Indonesian variety Silewah. In the future in characterisation of rice germplasm and interaction between rice germplasm specialists and rice molecular scientists, both in Japan and internationally, will be corner stones to securing rice genetic diversity and rice improvement in the next century.

Conservation of Natural Resources↗
PubMed1996

Hepatic extraction ratio of 5-fluorouracil in rats. Dose dependence and effect of uracil and interleukin-2.

The hepatic extraction ratios (EH) of 5-fluorouracil (FUra) in rats were studied to clarify the disposition of FUra in the liver. The EH of FUra in rats at infusion rates ranging from 0.375 to 3 mg/kg/min decreased from 0.750 to 0.225. The EH of values of tegafur, a pro-drug of FUra, were 0.076 to 0.103 over the range of infusion rates, 0.577 to 4.616 mg/kg/min, and were much lower than those of FUra. The EH of FUra at an infusion rate of 0.375 mg/kg/min combined with uracil (0.323 mg/kg/min) was 0.646, which was significantly lower than that of FUra alone, 0.750 (P < 0.001). The EH of FUra combined with interleukin-2 (IL-2) at an infusion rate of 7500 U/kg/min was significantly higher than that of FUra alone (P < 0.01). The dose dependence of the EH of FUra and the effects of uracil and IL-2 on the EH of FUra corresponded with clinical findings. These results suggest that this experimental model in rats may be useful for predicting the clinical pharmacokinetics and efficacy of FUra. We also studied the effect of IL-2 on the EH of mitomycin C (MMC). The EH of MMC combined with IL-2 was higher than that of MMC alone, but the difference was not significant.

Animals↗
PubMed1996

IL-2 perfusion to the liver augments the hepatic extraction rate of accompanying anticancer drugs.

A pilot study we conducted on hepatic infusion chemotherapy combined with interleukin-2 (IL-2) for metastatic liver malignancies revealed very encouraging results indicating that this treatment modality is more effective than either of the anticancer drugs used alone. To clarify the mechanisms underlying the synergism of these modalities, the pharmacokinetics of anticancer drugs were examined in a rat model. Adult rats were given 5-fluorouracil (5-FU) or mitomycin C (MMC) combined with various doses of IL-2 up to 7500 JRU/kg per minute for the measurement of hepatic extraction rates (HER). The HER of 5-FU was significantly increased (P < 0.01) in combination with IL-2 in a dose-dependent fashion while that of MMC also showed a tendency to increase. Thus, it is conceivable that the increase of vascular permeability caused by IL-2 results in augmentation of the HER of associated anticancer drugs. This effect may improve the delivery of anticancer drugs to the liver and alleviate general toxicity by reducing the amount of circulating anticancer agents.

Animals↗
PubMed1996

Second-look operation for recurrent colorectal cancer based on carcinoembryonic antigen and imaging techniques.

PURPOSE: The usefulness of postoperative carcinoembryonic antigen (CEA) monitoring and improvements in imaging techniques have renewed enthusiasm for second-look operations (SLO) as the most effective treatment for recurrent colorectal cancer by reresection following early detection. The aim of our study is to evaluate the role of CEA and imaging techniques-directed SLO. METHODS: Seven hundred fifty-six patients with Dukes Stages B and C, who had undergone curative resection, were monitored postoperatively using CEA and imaging techniques. An SLO was performed on any potentially resectable recurrence, and in addition, an SLO was done when a persistently rising CEA value was detected. RESULTS: Recurrence developed in 18.8 percent (142/756) of patients, and 90.8 percent (129/142) of the recurrences were detected within the first three years following curative resection. When comparing carcinomas of the colon with that of the rectum, the former were associated with significantly more hepatic and intraabdominal recurrences, whereas the latter had significantly more locoregional and pulmonary recurrences. Seventy-two patients underwent SLO. Of these patients, 54.2 percent (39/72) had all of their disease resected, and 1.4 percent (1/72) had no detectable disease at the SLO. Among the 142 patients with recurrence, 71 (50 percent) patients underwent SLO. The resectable group at SLO carried a significantly better survival than the unresectable recurrence group (41.3 vs. 5.2 percent; P<0.01). CONCLUSIONS: Complete removal of colorectal cancer recurrences by SLO, on the basis of postoperative, follow-up CEA and imaging technique findings, results in improved survival.

Actuarial Analysis↗
PubMed1996

Functional outcome after low anterior resection with low anastomosis for rectal cancer using the colonic J-pouch. Prospective randomized study for determination of optimum pouch size.

PURPOSE: Functional outcome after low anterior resection with ultralow coloanal anastomosis for rectal cancer is improved by construction of a colonic J-pouch vs. straight anastomosis. Optimum size of this pouch has yet to be determined. Therefore, we initiated a prospective, randomized trial using 5-cm and 10-cm pouches to determine this size. METHODS: Patients with tumors 5 to 10 cm from the anal verge were included in the study. Before a low anterior resection anastomosis was performed, patients were randomized to either a 5-cm J-pouch group (5-J group) or a 10-cm J-pouch group (10-J group). Functional assessments were performed one year postoperatively. Clinical functions were evaluated using a functional scoring system. Physiologic functions, such as sphincter and reservoir function, were evaluated by anorectal manometry and evacuation function by the balloon expulsion and saline evacuation tests. RESULTS: Forty patients among 43 randomized patients were assessed for functional outcome one year postoperatively (5-J group, n = 20; 10-J group, n = 20). The functional score was similar for the two groups, although reservoir function in the 5-J group was significantly less than in the 10-J group. Sphincter function was similar between the two groups. Evacuation function in the 5-J group was significantly superior to that in the 10-J group. CONCLUSIONS: The 5-cm J-pouch conferred adequate reservoir function without compromising evacuation.

Adult↗
PubMed1996

[Diagnosis and therapy for metastatic liver cancer].

Hepatic metastases occur frequently in patients with colorectal cancer. Patients with advanced cancer should be followed carefully after curative resection of the primary lesions for the early detection of the recurrence. If hepatic metastasis is suspected on the basis of rising CEA levels, more sophisticated imaging techniques, such as ultrasound, computed tomography, magnetic resonance imaging and hepatic angiography should be employed for the diagnosis. However, these tests are not cost-effective and not warranted on a routine follow-up basis. To be more cost-effective, a relatively simple and sensitive test or group of tests should be used. The authors have proposed that the basement membrane producibility of the primary lesion yields the most important information predicting a liver metastasis; the basement membrane producing cancer highly metastasizes to the liver. In contrast, more than 90% of non-producing cancer does not metastasize to the liver. The basement membrane producibility is easily examined by laminin staining. In the treatment of hepatic metastases, hepatic resection is the preferred approach when the metastases are located in a resectable segment or can be encompassed by as many as five wedge resections, but these scenarios are relatively uncommon. For unresectable disease, chemotherapy and intravenous and/or intra-arterial embolization are viable alternatives. Loco-regional treatment may offer a pharmacological advantage since a liver metastasis is almost exclusively fed by the hepatic artery. A pilot study we conducted on hepatic infusion chemotherapy combined with interleukin-2 (IL-2.MF) revealed very encouraging results (response rate: 76%), and further study in a prospective randomized trial confirmed this high response rate. Adjuvant IL-2.MF infusion therapy after curative resection of liver metastases is also effective for the prevention of recurrence in the residual liver. Based on the data, we conclude that multimodal treatments of hepatic resection and loco-regional infusion of immuno-chemotherapy (IL-2.MF) make it possible to control both resectable and unresectable liver metastases.

Animals↗
PubMed1996

Comparison between the Japanese general rules and the TNM system in the regional lymph node classification of carcinoma of the colon.

BACKGROUND: Metastasis to regional lymph nodes from carcinoma of the colon is an important prognostic factor. In the tumor, node, metastasis classification, node metastases are classified into four grades based on the number and distribution of metastatic nodes. In the Japanese General Rules for Clinical and Pathological Studies on Cancers of the Colon, Rectum and Anus, node metastases are classified into four grades based solely on the distribution of metastatic nodes. STUDY DESIGN: Based on the findings of node metastases in 152 patients with carcinoma of the colon obtained by the clearing method, the node classifications by the Japanese General Rules and tumor, node, metastasis classifications were compared. RESULTS: The case distribution by the Japanese General Rules grading was 38.2 percent in n(-), 30.3 percent in n1(+), 19.7 percent in n2(+), and 11.8 percent in n3(+) disease. In the tumor, node, metastasis classification, the distribution was 22.4 percent in pN1 and pN3 and 17.1 percent in pN2 disease. The five-year survival rate by the Japanese General Rules was 97.9 percent in n(-), 72.6 percent in n1(+), 51.2 percent in n2(+), and 30.0 percent in n3(+) disease, whereas in tumor, node, metastasis classification, this rate was 79.4 percent in pN1, 45.2 percent in pN2, and 44.8 percent in pN3 disease. CONCLUSIONS: In the classification of regional node metastases from carcinoma of the colon, the Japanese General Rules showed a wider range in distribution and 5-year survival rate compared with the tumor, node, metastasis system.

Colonic Neoplasms↗
PubMed1995

A high level of prostaglandin E2 (PGE2) in the portal vein suppresses liver-associated immunity and promotes liver metastases.

Prostaglandin E2 (PGE2) is generally accepted to be an immunosuppressant produced by cancer cells and their surrounding macrophages. Although several investigators have reported detecting high concentrations of PGE2 in the portal veins of patients with colorectal cancer, the relationship between these high concentrations of PGE2 in the portal vein and liver-associated immunity remains unclear. In this study, we attempted to determine if the portal administration of PGE2 suppresses the immune function of the liver in a rat model. Donryu rats were administered PGE2 via the portal vein for 7 days, following which the cytotoxic activity of hepatic sinusoidal lymphocytes (HSL) against natural killer (NK)-sensitive YAC-1 and rat syngeneic AH60C tumor cells was assessed. Purified HSL are spontaneously cytolytic; however, the continuous administration of PGE2 dramatically suppressed the cytotoxic activity of HSLs in a dose-dependent fashion. Flow cytometric analysis showed that the large granular lymphocyte (LGL) fraction, hepatic natural killer (pit) cells, and CD4-8+ killer/suppressor T cells were mainly reduced in number in the HSLs following PGE2 infusion. In this rat AH60C metastasis model, the continuous administration of PGE2 increased the number and size of metastatic tumor nodules in the liver, suggesting that high concentrations of PGE2 in the portal vein suppress liver-associated immunity and promote the formation of hepatic metastasis.

Animals↗
PubMed1995

[The development of serum alkaline phosphatase and gamma-glutamyl transpeptidase in early stages of primary biliary cirrhosis].

We carried out a retrospective study for the development of biochemical abnormalities in nine patients with early stages of primary biliary cirrhosis (PBC). All patients had elevated serum alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) levels when the diagnosis of PBC was obtained. In all cases, serum gamma-GTP levels initially increased, followed by the elevation of ALP. In the routine laboratory tests gamma-GTP is more sensitive than ALP for the screening for early PBC.

Aged↗
PubMed1995

Antibody to ras proteins in patients with colon cancer.

The current study examined sera from 160 colon cancer patients and 60 normal individuals to determine whether antibody to mutated p21 ras protein was present. Studies focused on the aspartic acid substitution at amino acid position 12 (denoted D12), one of the most common mutations in colon adenocarcinoma. IgA antibodies directed against mutated p21 ras-D12 protein were detected in 51 (32%) of 160 colon cancer patients, but only in 1 (2.5%) of 40 normal individuals. The greater incidence of antibody in cancer patients provides presumptive evidence that immunization to the ras proteins occurred as a result of the malignancy. Examination of sera for antibody reactivity to wild-type p21 ras protein (denoted p21 ras-G12) as well as p21 ras proteins bearing the D12, V12, S12, or L61 mutations showed that antibody detected was largely to normal segments of the p21 ras protein. Epitope mapping, using peptide neutralization assays with mutated or normal ras peptides as competitors, demonstrated that in 10 (67%) of 15 sera examined the antibody reactivity to p21 ras-G12 protein was neutralized by peptides near the carboxyl terminus of p21 ras protein, but not by peptides spanning the specific point mutation region. Antibody reactivities correlated with peripheral blood lymphocyte count, but did not correlate with patient age, sex, histology, stage, tumor locus, lymph node metastasis, or serum carcinoembryonic antigen.

Antibodies, Neoplasm↗
PubMed1994

Perineural invasion as a predictor of recurrence of gastric cancer.

BACKGROUND: Perineural invasion (PNI) plays a role in local invasion of pancreatic, biliary tract, and large intestine cancers and greatly affects the prognosis. Although PNI of gastric cancer has been reported rarely, the authors previously reported the usefulness of immunohistochemical staining with laminin in evaluating PNI. METHOD: PNI was studied histochemically in 283 patients with gastric tumors of T2 or greater depth of invasion resected between 1982 and 1989. The relationships between PNI and histopathologic findings, type of recurrence, and prognosis also were studied. RESULTS: Of the 216 patients who underwent resection for cure, 103 experienced tumor recurrence. Recurrence correlated significantly with lymphatic vessel invasion, lymph node metastasis, and PNI. Peritoneal recurrence was found in 65 (63.1%) of the 103 patients with tumor recurrence and correlated most significantly with PNI in T2 tumors. The 5-year survival rate was 71.3% for patients with PNI-negative tumors, significantly higher than the 5-year survival rate (23.7%) for patients with PNI-positive tumors. A multivariate analysis using a Cox regression model of the relationship between histopathologic findings and prognosis demonstrated that the presence of PNI had the greatest influence on prognosis. CONCLUSION: The evaluation of PNI is useful in determining the prognosis of gastric cancer of T2 class with no serosal invasion.

Adult↗
PubMed1994

Complete remission of liver metastases from colorectal cancer by treatment with a hepatic artery infusion (HAI) of interleukin-2-based immunochemotherapy: reports of three cases.

In an attempt to improve the therapeutic efficacy against liver metastases, a hepatic arterial infusion (HAI) of interleukin-2 (IL-2)-based immunochemotherapy for anticipating the regional potentiation of hepatic lymphokine-activated killer (LAK)/tumor-infiltrating lymphocytes (TIL) was initiated. We present herein the cases of three patients with multiple liver metastases from colorectal cancer in whom complete remission was achieved by treatment with an HAI of IL-2 in combination with mitomycin C (MMC) and 5-fluorouracil (5-FU). These patients received an HAI of IL-2 at 8 x 10(5) JRU, 5-FU at 250 mg daily, and MMC at 4 mg once weekly for 3 weeks, being the induction regimen, after which they were discharged on maintenance therapy consisting of IL-2 at 2 x 10(6) JRU, 5-FU at 250 mg twice weekly, and MMC at 4 mg once weekly. It was evident from the liver CT scan taken after 2-3 months that the metastatic foci seen before therapy had clearly disappeared, while the serum carcinoembryonic antigen (CEA) had decreased to normal levels in all three patients. Pancytopenia was seen in one patient, but other laboratory studies of the hepatic and renal parameters were normal. The total lymphocyte count in the peripheral blood showed a mild decrease, while the lymphocyte phenotype study showed a notable increase in CD4+ cells and a decrease in CD8+ cells, with an elevation of a 4/8 ratio, in all cases during therapy. One patient relapsed with pelvic recurrence 14 months after the initiation of therapy, but the other two patients are still in remission 25 and 22 months after the initiation of therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Effect of packed red cell and whole blood transfusion on liver-associated immune function.

In order to clarify the effect of allogeneic blood transfusion on liver metastases from primary cancer, liver-associated immune function after blood transfusion was evaluated in a murine model. Hepatic sinusoidal lymphocytes (HSL) were strongly cytotoxic to conventional natural killer cell-sensitive target (YAC-1), as well as to natural killer cell-resistant solid adenocarcinoma cells (colon 26), compared with splenic lymphocytes. Allogeneic whole blood transfusion strikingly suppressed the cytotoxic activities of HSL. Red blood cell transfusions also suppressed cytotoxicity to the same degree. In an animal model, allogeneic transfusion increased the rate of liver metastases. Flow cytometric analysis showed that transfusion caused a temporary decrease in the class II antigen positive cell fraction, mainly Kupffer's cells. This phenomenon occurred in parallel with changes in hepatic antitumor activity, indicating the possible importance of the involvement of Kupffer's cell in the development of the killer activity of HSL. These results suggest that blood transfusion may be a significant risk factor for hepatic metastasis by transiently suppressing the immunocompetence of the liver.

Animals↗
PubMed1994

[Selective effectiveness of galactose-containing liposome IL-2 on liver lymphocytes].

We have performed immunochemical intraarterial infusion immunochemotherapy containing IL-2, mitomycin C and 5-FU as the main active ingredient for metastatic liver tumor and obtained favorable results. However, we are obliged to perform intra-hepatic arterial infusion once or twice a week, because of the short half-life of IL-2. Thus, we are using a drug delivery system to activate lymphocytes of the liver. We noticed many galactose-receptors in the liver and prepared galactose-containing liposome preparations using various carriers/bases. As a result, galactose-containing liposome preparations showed the highest accumulation and the highest localized enhancing effect on the antitumor activity of lymphocytes in the liver sites.

Animals↗
PubMed1993

A successful liver metastasis model in mice with neuraminidase treated colon 26.

The aim of this study was to establish a reproducible and quantitative liver metastasis model in mice. The in vitro colon 26 (C-26) cultured cell line was initially taken from an in vivo transplantable C-26 adenocarcinoma tumor mass using the standard enzymatic treatments, collagenase and DNAse. In vitro cultured cells x 10(4) were introduced into the portal vein of syngeneic BALB/c mice to induce liver metastases and, 3 weeks later metastatic foci were found in approximately 50% to 70% of the mice. In contrast, C-26 cells desialylated by neuraminidase (Nase) treatment greatly increased the incidence of hepatic metastases with countable hepatic colonies being found in all mice (100%). This result seems to be related to the liver-characteristic D-galactose receptors, since pre-injection with an excess amount of galactocerebroside completely prevented tumor colonization in the liver. Thus, although we cannot disregard the involvement of other adhesion molecules in this system as yet, our experimental model may become a useful tool for the analysis of hepatic metastases from colon cancer in the future.

Animals↗