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Biomedical subjects

I Miyazaki

Publications and source records attributed to I Miyazaki.

At least 253 records · Page 14Linked to original sources

[In vitro chemosensitivity test using collagen gel matrix for human gastric carcinomas].

We evaluated the usefulness of in vitro human tumor culture system using a specialized collagen gel matrix derived from pigskin as a chemosensitivity test for human gastric cancer including scirrhous type. Seven xenograft tumors derived from human gastric cancers were examined with this system and compared with the data obtained by the nude mouse chemosensitivity assay. Xenograft tumors exhibited an in vivo like three-dimensional growth on the collagen gel matrix. There were very close associations between the results obtained by this assay and those obtained from the same drug by the nude mouse assay. Moreover, this system seemed to be useful for prediction of drug sensitivity for scirrhous type gastric cancers. This in vitro assay system has an advantage for chemosensitivity test, because of its convenience, rapidity, and in vivo like three-dimensional tumor growth.

Adenocarcinoma, Scirrhous↗

[Study of para-aortic lymph node metastasis for advanced gastric cancer on consecutive lymph node slices].

Para-aortic lymph nodes (No. 16) from 21 patients with advanced gastric cancer who underwent extensive lymph node dissection, were sliced consecutively at intervals of 50 mu to study minute metastasis of No. 16 lymph nodes. Twenty-six of 30 metastatic lymph nodes had minute involvement, in which carcinoma cells were detected in marginal sinus of lymph node, microscopically. The rate of the metastases to No. 16 lymph nodes was 19% among N0-3 cases by conventional method (not consecutive slices). On the contrary, the percentage of metastasis to No. 16 lymph nodes by consecutive slices was 33% among N0-3 cases. Therefore, No. 16 nodes are involved in metastasis at high rate at operation and the extensive lymph node dissection including No. 16 nodes (R4) will be recommended to prevent lymph node recurrence caused by such a minute metastasis.

Aorta↗

[Chemosensitivity test for gastric cancer by in vitro MTT assay].

In vitro MTT assay was applied for examining chemosensitivity with 104 samples; 56 primary tumors, 31 lymph node, 9 liver, and 8 peritoneal metastases, obtained from 87 patients with advanced gastric carcinoma. The rate of effectiveness of various anticancer drugs were as follows; etoposide, 87.7%; cisplatin, 55.1%; mitomycin C, 51.5%; pirarubicin, 50.0%; aclarubicin, 48.8%; carboquone, 31.8%; doxorubicin, 20.3%; and 5-fluorouracil, 12.9%. Etoposide was found to be most effective against gastric carcinoma in this test. Concerning with the metastatic lesions, liver metastases were resistant to all tested drugs. On the other hand, peritoneal metastases were sensitive to etoposide, mitomycin C, and pirarubicin. The results indicate heterogeneity of the chemosensitivity between primary and metastatic lesions, and it was supposed that etoposide might be useful against human gastric cancer.

Antineoplastic Agents↗

[Clinical effect of postoperative adjuvant chemotherapy for advanced colorectal cancer--comparisons of between tegafur (FT) and UFT].

A randomized controlled study was conducted on a FT 600 mg/day daily oral administration group and a UFT 400 mg/day daily oral administration group as an adjuvant chemotherapy after curative operation for colorectal cancer patients with injection of Mitomycin 30 mg (20 mg during operation and 10 mg on the day following), and the results were examined. FT and UFT were administered orally for one year from the 3rd week after operation. The 5-year survival rate was slightly higher in the UFT administration group. Five-year survival was 82.7% for colon cancer and 82.1% for rectal cancer in the UFT administration group, against 72.6% and 72.0 % in the FT administration group. The same trend was observed when the survival rate was studied by various factors such as the size of tumor, depth of cancer invasion of the wall, histological type, lymph node metastasis, vascular invasion and the degree of progression. There was no difference between both groups in the patterns and times of recognition of the recurrences and in the appearance rate of side effects. The results suggest that UFT 400 mg/day is equal to or better than FT 600 mg/day in therapeutic effect for colorectal cancer patients, although the UFT dose is only 2/3rd the FT dose.

Administration, Oral↗

[Candidiasis in the field of gastroenterological surgery].

Postoperative candidiasis in the gastroenterological surgery has an increasing tendency with poor prognosis particularly in generalized cases. Candida is difficult to be specified as infectious agent only by culture findings, and has a problem on rapidity and sensitivity. Furthermore, also as for the time starting antifungal treatment, the start after the blood culture has given positive result is problematic. We analyzed the present state of candidiasis in our department and studied its background factors. Totaling of 4,424 samples from all of bacterial and fungal culture tests performed at our department for recent 9 years revealed detection of Candida with the incidence of 24%. The incidence was about 2.5 times increased in the former half of the period as compared with the later half of the period. The background factors were intravenous hyperalimentation, major operations (long operative time, insertion of many drains), splenectomy, pancreatectomy, intensive chemotherapy, radiation therapy, hyperthermia therapy, aging, continuous use of steroids, etc. Then, we determined concentrations of beta-D-glucan, a fungal component, and evaluated the results since it is being applied to early diagnosis of candidiasis. We performed early antifungal treatment before confirmation of positive culture finding in high risk group of candidiasis and obtained effective results.

Candidiasis↗

[In vitro chemosensitivity test using collagen gel matrix for human gastric carcinomas].

The usefulness of an in vitro human tumor culture system using a specialized collagen gel matrix derived from pig skin was retrospectively evaluated as a chemosensitivity test for human gastric carcinomas. Seven xenograft tumors derived from human gastric cancers were examined by this system (CGM assay) and compared with the data obtained by a nude mice assay (NM assay) and a succinic dehydrogenase inhibition test (SDI test). Xenograft tumors had three-dimensional growth on the collagen gel matrix like that in vivo. There was increasing cell kill with rising cytotoxic drug concentration. When drug sensitivity was evaluated as effective based on an inhibition rate of 40% or more in the CGM assay, drug sensitivity as measured by the CGM assay corresponded with that measured by the NM assay for all xenograft tumors but not the SDI test. This system could be applied for chemosensitivity test of scirrhous gastric carcinomas. It was suggested that the CGM assay may be more like an in vivo like chemosensitivity test and clinically useful testing for the patients with gastric cancer, including scirrhous one.

Animals↗

Relation of proliferative activity to survival in patients with advanced gastric cancer.

The proliferative activities of 98 biopsied specimens of advanced gastric cancers were measured by the in vitro bromodeoxyuridine (BrdU) labelling method. BrdU labelling indices (LIs) varied from 4.8 to 45.1%. There was no correlation of BrdU LIs and histological type, distant metastasis, serosal invasion, macroscopic type or tumor size. However, BrdU LIs of tumors with lymph node metastases were significantly higher than those without them. Patients with tumors showing high BrdU LIs had a three-fold relative risk of death, as compared with those showing low BrdU LIs. When the BRdU LIs and all the clinicopathological parameters were entered simultaneously into the Cox model, BrdU LIs, peritoneal dissemination and serosal invasion emerged as independent prognostic parameters. These results indicate that the in vitro BrdU labelling method using biopsied materials may be useful in predicting lymph node metastasis preoperatively and designing operative procedures for individual patients.

Bromodeoxyuridine↗

Pancreatojejunostomy.

Pancreatoduodenectomy is a complex procedure associated with considerable mortality and morbidity. Pancreatojejunostomy is probably the main cause of morbidity, and controversy concerning the best type of reconstruction still exists. In this report the technique of pancreatojejunostomy is demonstrated. An end-to-side pancreatojejunostomy is performed on all patients. For patients with a pancreatic duct of less than 4 mm in diameter, the top of the pancreatic duct is inserted into a stab-wound of jejunum. It is secured with a purse-string suture. Furthermore, two layers of reinforcement are done. By using this technique, an end-to-side anastomosis was done on patients with soft glands and small ducts. In patients with a pancreatic duct greater than 4 mm, a three-layer anastomosis is done between pancreas and jejunum. This is a technique that allows the performance of an end-to-side anastomosis regardless of the pancreas consistency or pancreatic duct diameter.

Anastomosis, Surgical↗

[Flow cytometric analysis of DNA ploidy pattern in advanced gastric cancer and its relationship with prognosis].

Cell nuclear DNA content was determined by flow cytometric analysis in 270 patients with advanced gastric cancer. Aneuploid DNA content was observed in 150 patients (55.6%). The DNA ploidy pattern was the third significantly prognostic factor behind peritoneal dissemination and liver metastasis in Cox regression multivariate analysis. About the relationship between DNA ploidy pattern and other prognostic factors, peritoneal dissemination and wall invasion ratio of aneuploid were significantly higher than those of diploid (p less than 0.01). Five-year survival rate of diploidy patients was significantly higher than that of aneuploidy patients. In stage I, five-year survival rate of patients with diploid tumor was 83.3% and that of patients with aneuploid tumor was 70.0%. In stage II, that of patients with diploid tumor was 81.3% and that of patients with aneuploid tumor was 66.7%. In stage III, that of patients with diploid tumor was 71.2% and that of patients with aneuploid tumor was 25.1%. In stage IV, that of patients with diploid tumor was 31.6% and that of patients with aneuploid tumor was 2.6%. Furthermore in the curative case, that of patients with diploid tumor was 77.2% and that of patients with aneuploid tumor was 48.2%. Aneuploid case has significantly worse prognosis in curative operation.

Adult↗

[The surgical results of pancreatoduodenectomy and total pancreatogastrectomy combined with autotransplantation of the distal half of the pancreas for the treatment of advanced gastric cancer located in the lower half of the stomach].

In the last 16 years we employed pancreaticodudenectomy (PD) on 27 patients with cancers of the distal third of the stomach, associated with duodenal invasion, invasion to pancreatic head, or n3 metastasis. More recently, total gastrectomy and total pancreatectomy combined with heterotopic autotransplantation of the distal pancreas (TGTP) was performed in 7 patients with n4 metastases. These cases were compared with 56 patients who underwent subtotal gastrectomy (SG) in the same period. When the survival rates were compared, PD provided better long-term results than SG, especially on the patients with tumors infiltrating into the pancreas head. On the contrary, there was no significant survival advantage in patients with duodenal invasion or n3 metastasis between PD group and SG group. TGPT showed the longest survival for the patients with n4 metastasis. These results indicate that PD is a rational and safe method for the treatment of gastric cancer infiltrating into the pancreas head. In addition, TGTP may be the most radical procedure for the treatment of gastric cancer with n4 metastases.

Duodenum↗

[Application of anti-p-105 monoclonal antibody to analysis of mode of action of antitumor agents].

For the elucidation of the mode of action of anti-tumor agents, the cell cycle analysis of etoposide and podophyllotoxin was examined by means of the multiparameter flow cytometry using an anti-p-105 monoclonal antibody. The p-105 is one of the proliferation associated nuclear antigens and its expression increases with a cell cycle progression, especially in mitotic phase. Thus, we have applied its anti-monoclonal antibody to the discrimination between M and G2 phases of the gastric cancer cells. The results revealed that etoposide caused a G2 block and retarded an S phase transition, and podophyllotoxin caused both G2 and M phase blocks in the gastric cancer cells. This cell cycle analysis using an anti-p-105 monoclonal antibody would be a useful analysis of the antitumor agents, especially for M phase analysis of human cancer cells because of its rapidity and convenience.

Antibodies, Monoclonal↗

Growth fractions in gastric carcinomas determined with monoclonal antibody Ki-67.

The growth fractions of 101 gastric carcinomas were determined in situ by immunostaining with the monoclonal antibody Ki-67 and the results correlated with the histopathologic findings, bromodeoxyuridine (BrdU) labeling index, and DNA ploidy pattern. DNA ploidy patterns were determined by flow cytometric analysis. The Ki-67 labeling rates are rated from 4.6% to 82% (mean, 22%). A significant correlation was found between Ki-67 labeling rates and BrdU labeling indices. Sixty-seven percent of tumors with lymph node metastases showed Ki-67 labeling rates of less than 22%, whereas 33% of tumors without lymph node metastases showed Ki-67 labeling rates of less than 22%. There was a significant correlation between these two groups. Tumors with vessel invasion more often have higher Ki-67 labeling rates than those without vessel invasion. By the DNA ploidy classification, the mean Ki-67 labeling rates of aneuploid tumors was significantly higher than that of diploid tumors. This method yielded similar results to those obtained by BrdU labeling and flow cytometric study. The measurement of Ki-67 labeling rates may be useful to decide the therapeutic modalities.

Antibodies, Monoclonal↗

Retrospective analysis of the prognostic significance of DNA ploidy patterns and S-phase fraction in gastric carcinoma.

Paraffin-embedded tumor samples from 493 gastric carcinoma patients were analyzed by DNA flow cytometry. The results were correlated with clinicopathological findings and S-phase fractions measured by in vivo bromodeoxyuridine (BrdUrd) labeling. Of the 493 patients, 183 (37%), 225 (46%), and 85 (17%) showed diploidy, single DNA-aneuploidy, and DNA-multiploidy patterns, respectively. When the DNA histogram and all the clinicopathological parameters were entered simultaneously into the Cox regression model, DNA ploidy, liver metastasis, peritoneal dissemination, and nodal status emerged as independent prognostic parameters. The relative risk of death was twofold higher in single DNA-aneuploid and threefold higher in DNA-multiploid tumors than in DNA-diploid tumors. BrdUrd labeling indices (LIs) also proved to be an independent prognostic factor. Multiploid tumors showed the highest median BrdUrd LI associated with the most frequent peritoneal dissemination and liver metastasis. The simultaneous evaluation of DNA ploidy patterns and BrdUrd LIs gave more prognostic information than the determination of tumor DNA ploidy only. Namely, DNA diploid, together with low BrdUrd LIs, was associated with favorable prognosis, whereas DNA aneuploid with high BrdUrd LIs was related to the poorest prognosis. These results indicate that DNA ploidy and BrdUrd labeling indices may be possibly useful prognostic factors for gastric carcinoma.

Aneuploidy↗

Prognostic value of S-phase fraction and DNA ploidy studied with in vivo administration of bromodeoxyuridine on human gastric cancers.

The authors studied the prognostic values of DNA ploidy pattern and proliferative activity with in vivo administration of bromodeoxyuridine in human gastric cancers. Fresh specimens surgically removed from 117 patients with gastric cancer were investigated by flow cytometric study using a monoclonal antibody to bromodeoxyuridine. DNA ploidy patterns were classified into four types according to the bivariate BrdUrd/DNA distribution: D1, tumors with single diploid population; D2, tumors which showed mosaic of diploid and aneuploid population; A1, tumors with single aneuploid population; and A2, several aneuploid populations without diploid population. The numbers of cases of each ploidy pattern were as follows: D1, 36 cases (30.8%); D2, 38 cases (32.5%); A1, 15 cases (12.8%); and A2, 27 cases (23.1%). DNA ploidy pattern and S-phase fraction (SPF) showed no relation with clinicopathologic findings, except for type A2. In type A2, lymph node metastasis and lymphatic vessel invasion were observed more often than type D1. The SPF calculated from the bivariate BrdUrd/DNA distribution was higher in aneuploidy (D2, A1, and A2) than in diploidy (D1) (P less than 0.01). Also, A2 exhibited a higher SPF than A1 (P less than 0.01). Furthermore, SPF correlated with DNA index significantly (P less than 0.01). Patients who showed aneuploid tumors, DNA ploidy type A2, or SPF of more than 10% survived 3 years less than those with diploid tumors, DNA ploidy type D1, or SPF of less than 10%, respectively (P less than 0.05). By analyzing with the Cox's proportional hazard's model, it is revealed that DNA ploidy and SPF are one of the independent factors of prognostic significance. The results indicated that the patients with aneuploid tumors or highly proliferative tumors had a poor prognosis and that DNA ploidy pattern and SPF were useful prognostic factors for gastric cancers.

Bromodeoxyuridine↗

Bilateral cervical lymph node metastases in well-differentiated thyroid cancer.

We analyzed the regional lymph node metastases of 98 patients with thyroid cancer who underwent bilateral modified neck dissection. Bilateral jugular lymph node metastases were frequent in patients with papillary carcinoma of the thyroid, especially in those patients with obvious carcinoma in both lobes of the gland, cancer arising in the isthmus, clinically detectable bilateral lymphadenopathy, and recurrent thyroid cancer. In patients whose cancer was clinically confined to one lobe, and where there were no obviously enlarged contralateral lymph nodes, the occurrence of contralateral jugular lymph node metastasis was significantly correlated with the contralateral paratracheal lymph node metastasis. The bilateral lymphadenectomy appears to be appropriate in these instances.

Adenocarcinoma↗