[Squamous cell carcinoma of the small bowel, colon and rectum].
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Biomedical subjects
Publications and source records attributed to A Nakayoshi.
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PCNA is known as a cell cycle-related nuclear antigen. We stained PCNA immunohistochemically, and examined whether or not PCNA expressive rate could be applied clinically for a biological parameter of the histopathological effects in preoperative chemotherapy. PCNA was stained in proliferating cell by measuring nuclear DNA simultaneously. The most suitable fixation time in PCNA expression was 24 hours. On the examination of fixation fluid, ethanol was considered to be more suitable than buffer formaldehyde because PCNA expressive rate in ethanol correlated to BrdU labeling index with statistical significance. We examined PCNA expressive rate in gastric carcinomas. In the group whose histopathological effects of preoperative chemotherapy was recognized to be positive, PCNA expressive rate was significantly lower than in the group of negative effect. We measured thymidylate synthetase inhibition rate (TSIR) in the cases of preoperative oral administration of 5-FU, and the significantly negative correlation was seen between TSIR and PCNA expressive rate in the cases of differentiated adenocarcinoma (p < 0.05). The proliferating activity was recognized to be lower in the cases of higher inhibitional effect for DNA synthesis. PCNA expressive rate was considered to be a more effective and objective biological parameter on the evaluation of malignant potential in gastric carcinoma.
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Dogs weighing between 10 and 15 kg were used, and cisplatin was given at a dose of 2 mg/kg. The dogs were infused ip with either 100 ml (A groups) or 200 ml (B groups) of physiological salt solution containing cisplatin. The cisplatin concentrations in serum (peripheral and portal blood), and liver tissues were measured with limited filtration using MPS of AMICON (free-CDDP). The total CDDP concentration was also determined. Blood was collected at 30 minutes, and 1, 2, 3, 4, 5 and 6 hours after ip administration. The following results were obtained: 1) A high concentration of free-CDDP (AUC) was observed in the portal blood of A groups. 2) Peripheral serum level (total-CDDP) was increased in the B groups. 3) Total CDDP level within the liver tissues was higher in the A groups. It is concluded that ip cisplatin therapy with moderate volume solution may be effective for liver metastasis of gastric cancer for delivery to the liver tissue.
Surgery is still the treatment of choice in gastric cancer. However, despite the availability of extended surgical procedures, the majority of patients with stage IV gastric cancer have a poor prognosis. Therefore, other treatment modalities, especially systemic chemotherapy, have been investigated intensively. The recent successes achieved with combination chemotherapy regimens, such as EAP, strongly indicated that gastric cancer is chemosensitive. We also treated previously untreated patients with advanced and recurrent gastric cancer. Chemotherapy of CDDP 30 mg/m2 was given intravenously (i.v.) on day 1; etoposide 70 mg/m2 (i.v.) on days 2 to 4; and 5-FU 500 mg/m2 (i.v.) on days 2 to 5. The courses were repeated every 3 weeks. FEP induced an overall response rate of 25%, including 25% PR (primary tumor) and 25% PR (liver-metastasis). The median survival rate for all patients was 7.3 months and partial responses were seen in three patients with a median response duration of 13.1 months. In 2 patients with PR of primary tumor, one patient underwent a second-look operation and one patient refused an operation. Therefore, ten of 12 patients entered have died, and 2 patients remain alive. We concluded that FEP regimen can be useful in the treatment of advanced and recurrent gastric cancer. Moreover, the preoperative use of effective regimens seems to improve prognosis.
The pharmacokinetics of ip cisplatinum (100 mg/body) was studied in 10 patients with advanced gastric cancer. Five patients were administered ip-cisplatinum with STS and another 5 patients were given the same without STS. As a result, 1) the level of free-CDDP in ascites fluid was significantly elevated after administration, showing that free-CDDP possessing anti-tumor activity persisted in the ascites fluid for a long time and reached the peak concentration 30 minutes after administration. 2) The free-CDDP transferred into the blood after administration also persisted for a long time in parallel with changes in the free-CDDP level in the ascites fluid. 3) The AUC, MRT and VRT of the free-CDDP concentration in the peritoneal cavity after ip administration of CDDP were high, clearly indicating the direct effect on peritoneal concentration. 4) The AUC, MRT and VRT of free-CDDP in the venous phase after ip administration of CDDP were higher than after its iv administration, suggesting that effects equivalent to or greater than those of the iv route drug can be expected in the venous phase. 5) The frequency of side effects induced by the combination of STS was lower than that of side effects induced by the administration without combined STS. Much larger doses of CDDP may be given ip by combining with STS.
Chemotherapy for colorectal cancer with liver metastases following surgical operation for primary tumor should be selected following surgical intervention. Continuous infusion chemotherapy using an infusional port was selected for unresectable metastasis due to colorectal cancer in our department. The catheter was placed in the hepatic artery through a gastroduodenal by operative procedure. 5-fluorouracil (5-FU) and mitomycin C (MMC) were used as chemotherapeutic agents. After MMC was given at 10 mg/body by bolus, administration of 5-FU was continuously infused at 250 mg/day for 2 weeks, followed by a 2-week interval. Drug administration was done by implanted pump hepatic arterial infusion. Seventeen of the patients with liver metastasis underwent this chemotherapy from 1986 through 1990. Results of the infusion chemotherapy were as follows. Value of serum CEA decreased until two courses were given in all cases. In 11 cases, the tumor size on CT was remarkably smaller. In these patients, however, there were many complications due to the catheter used for catheter replacement, drug leakage, drug extravasation and so on. We concluded that although this chemotherapy was very effective, the method should be improved in terms of the material, the location of catheter tip and the like.
The pathogenesis of cholesterol cholelithiasis in man is probably multifactorial and the mechanism by which gallbladder stasis occurs in gallstone patients has not been studied in detail. In the present study, time-dependent changes in gallbladder motility of the Richardson Ground Squirrels were investigated. 100 of animals were examined for their contractile responses of gallbladders to CCK-OP and Ach in vitro. Also, biochemical changes of serum and bile were investigated. There were no significant differences in motility of gallbladders to CCK-OP or Ach between control and cholesterol-fed animals. The results of this study indicate that gallbladder muscle contractility remains unchanged during the dietary induction of cholesterol gallstones in the Richardson Ground Squirrel.
Two rare cases of multiple neoplasms occurring in association with anomalous arrangement of the pancreatobiliary duct system (PBD) are reported. Ultrasonography, computed tomography and endoscopic retrograde cholangiopancreatography revealed cholecystic tumor in the first case, and multiple choledochocholecystic tumors in the second case. In the first case, pancreatic tumor was discovered two years after cholecystectomy. In the second case, a pancreatic tumor was discovered incidentally in the removed pancreatic head after the operation. The histology of all of these biliary and pancreatic tumors revealed papillary adenocarcinoma in both patients, and additionally small pancreatic endocrine tumors were found in the first case. Postoperative prognosis was comfortably favorable in both patients. In a literature survey, two other cases of double carcinomata associated with anomalous PBD were found, in which the tumors showed the same histology of papillary adenocarcinoma and the postoperative prognoses were also good. These mutual clinicopathological features appear to suggest that this abnormal condition acts as a carcinogenetic risk factor in the pancreatic duct and the biliary duct system, and may finally cause multiple carcinomata in the PBD.
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