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Biomedical subjects

C Konno

Publications and source records attributed to C Konno.

At least 37 records · Page 2Linked to original sources

[Clinical results of intraperitoneal hyperthermic perfusion combined with surgery in patients with peritoneal recurrence from gastric cancer].

Six patients with peritoneal recurrence after radical operation for gastric cancer were treated by an intraperitoneal hyperthermic perfusion (IPHP) combined with surgery (IPHP group). Immediately after surgery, a 2-hour IPHP was performed, using a perfusate containing 10 micrograms/ml of MMC, warmed at the inflow temperature of 46.5 +/- 1.1 degree C. Within the same period of time, 5 patients with intra-abdominal recurrent gastric cancer (control group) were treated by an intraperitoneal administration of MMC 10 mg combined with surgery. These 11 patients had malignant peritoneal effusion and, although in 3 of the control group, ascitic effusion did re-accumulate rapidly soon after surgery, the 6 patients of IPHP group did not re-accumulate post-hyperthermically. The average survival duration of IPHP group is 13.6 +/- 10. 6 months, whereas that for controls is 3.0 +/- 2.1 months. Again, the survival rate for IPHP group surpassed that for controls at p = 0.012 and p = 0.008, in a generalized Wilcoxon method and Logrank method, respectively. Post-hyperthermically, hypoproteinemia and thrombocytopenia occurred transitorily. These results show that IPHP using MMC combined with surgery is a safe, reliable treatment for patients with peritoneal recurrence due to gastric cancer.

Combined Modality Therapy↗

[Clinical evaluation of recurrent patterns of gastric cancer after intraperitoneal hyperthermic perfusion].

The patterns of recurrence and the prognosis of 24 gastric cancer patients with peritoneal seeding and/or serosal invasion, who underwent gastrectomy followed by intraperitoneal hyperthermic perfusion (IPHP), were studied in comparison with 23 gastric cancer patients given surgery alone (controls). With respect to 22 patients with peritoneal seeding, all of 8 patients in the control group died of re-accumulation of ascitic effusion, whereas of 14 patients in the IPHP group, 3 died of peritoneal recurrence, 2 of intraperitoneal tumors, 1 from pleural metastasis, and 1 of liver metastasis. The remaining 7 cases are alive without a sign of recurrence. Again, with respect to 25 patients with large serosal penetration of cancer, 7 of 15 patients in the controls died of peritoneal recurrence, whereas this was never observed in the IPHP group. As to the relation of histology and prognosis, while the poorly differentiated adenocarcinoma and signet ring cell carcinoma had poor prognosis in the controls, the same patterns in the IPHP group proved not to be so unfavorable. Since a few given IPHP resulted in hepatic metastasis and/or nodal involvement, adjuvant treatment will be required. The survival rate for the IPHP group was significantly better at p = 3.43 x 10(-2) than in controls.

Aged↗

[Clinical effect of intraperitoneal hyperthermochemotherapy on the survival rate for advanced gastric cancer patients].

Intraperitoneal hyperthermic perfusion (IPHP) was performed right after surgery for 31 advanced gastric cancer patients with serosal invasion and/or peritoneal dissemination. The survival rate in the IPHP group, was compared with that in the control group, 30 patients who underwent surgery alone within the same period of time. The 1-year survival rates for IPHP group and control group were 81.9% and 40.3%, respectively. The 2-year survival rates were 52.1% and 11.8%, and the 3-year survival rates were 26.1% and 0%, respectively. The survival rate for IPHP group was better than that for control group, with p = 1.46 x 10(-4). IPHP and control group with peritoneal dissemination included 21 and 9 patients respectively, and 50% survival rates were 18 months and 4.2 months, respectively. IPHP and control group with serosal invasion included 10 and 21 patients, respectively, and 8 out of 10 patients survived in the IPHP group, while 17 out of 21 patients died in the control group. These results suggest that IPHP is effective for gastric cancer patients with peritoneal dissemination and/or serosal invasion.

Aged↗

Clinical trial with surgery and intraperitoneal hyperthermic perfusion for peritoneal recurrence of gastrointestinal cancer.

To treat six patients with peritoneal recurrence after radical operation for gastrointestinal cancer, an intraperitoneal hyperthermic perfusion (IPHP), combined with surgical resection of recurrent tumors, intestinal by-pass anastomosis, or both, was carried out. Immediately after complete resection of the intraperitoneal recurrent tumors, a 2- to 3-hour IPHP was performed under hypothermic general anesthesia at about 32 degrees C, using a perfusate containing 10 micrograms/ml or 20 micrograms/ml of mitomycin C (MMC) warmed at the inflow temperature of 46.6 degrees C to 46.9 degrees C. The apparatus used for IPHP was designed for intraperitoneal perfusion as a closed circuit. Although five of the six patients had a malignant peritoneal effusion at the time of admission, the effusion disappeared soon after IPHP, and no cancer cell was present in the lavage from Douglas' pouch. The other patient had a recurrent tumor at the anastomotic region after low anterior resection for rectal cancer and complete resection of the recurrent tumor, combined with IPHP, was carried out. One patient with a recurrent gastric cancer died of hepatic metastasis and cancerous pleuritis 5 months after this treatment, and the other five are in good health 12.8 +/- 5.1 months after IPHP. On the other hand, five patients with intra-abdominal recurrent gastric cancer, who received only surgical treatment within the same period of time, died 3.0 +/- 2.1 months after the surgery. Postoperatively, in the six patients with IPHP, transitory hepatic dysfunction, hypoproteinemia, and thrombocytopenia occurred. These results show that IPHP using MMC combined with surgery is a safe, reliable treatment for patients with peritoneal recurrence of gastrointestinal cancer.

Adult↗

Thermotolerance of xenografted human gastric cancer.

To compare the thermotolerance in vivo of two human gastric cancers with different doubling times, the xenografted tumors were warmed twice at 43.5 +/- 0.1 degree C in a water bath for 20 minutes at a predetermined interval. In the tumors with doubling times of 5.2 and 10.9 days, a 7-day interval heat treatment resulted in a prolongation in tumor tripling times by 156 per cent and 132 per cent, respectively, compared with a single heat treatment for 40 minutes. On the contrary, two heat treatments given at intervals of 3 to 5 days had a short tumor tripling time, compared to that of the 40-minute single treatment. Thus, the thermotolerance of these human gastric cancers gradually increased to a maximum within a 3- to 4-day interval and disappeared completely after a 7-day interval. These results indicate that the times required to reach maximal thermotolerance in these human gastric cancers were longer than those previously demonstrated for human and rodent cancer cell lines in vitro. The development and decay of thermotolerance in these human gastric cancers need to be considered in the design of multiple-fractionated regimens.

Adenocarcinoma↗

Mechanisms of hypoglycemic activity of aconitan A, a glycan from Aconitum carmichaeli roots.

Aconitan A did not affect plasma insulin levels in normal, glucose-loaded and alloxan-induced hyperglycemic mice and gave no influence on insulin binding to isolated adipocytes. Aconitan A exerted no effect on the activities of hepatic hexokinase, glucokinase, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase, whereas it significantly increased hepatic phosphofructokinase activity. Although the activity of hepatic glycogen synthetase showed a tendency to increase, the activity of liver phosphorylase and glycogen content were unchanged by aconitan A. Aconitan A did not change the total cholesterol and triglyceride contents of plasma and liver.

Adipose Tissue↗

Isolation and hypoglycemic activity of trichosans A, B, C, D, and E: glycans of Trichosanthes kirilowii roots.

The non-dialyzable portion of the water extract of the Oriental crude drug "karokon", the roots of Trichosanthes kirilowii, was found to reduce the plasma glucose level in mice. Activity-guided fractionation of this non-dialyzable portion led to the isolation of five glycans termed as trichosans A, B, C, D and E, showing hypoglycemic actions in normal mice. The main glycan, trichosan A, also exhibited activity in alloxan-induced hyperglycemic mice.

Animals↗

Mechanisms of hypoglycemic activity of ganoderan B: a glycan of Ganoderma lucidum fruit bodies.

Ganoderan B increased the plasma insulin level in normal and glucose-loaded mice but elicited no effect on insulin binding to isolated adipocytes. Administration of ganoderan B elicited significant increases of the activities of hepatic glucokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase, decreased the hepatic glucose-6-phosphate and glycogen synthetase activities and did not affect the activities of hexokinase and glycogen phosphorylase. Ganoderan B reduced the glycogen content in the liver but had no influence on total cholesterol and triglyceride levels in the plasma and liver.

Animals↗

[Pharmacokinetic analysis in intraperitoneal hyperthermic perfusion using mitomycin C in far-advanced gastric cancer].

Postoperative intraperitoneal hyperthermic perfusion (IPHP) using MMC was performed with marked success on 15 gastric cancer patients with peritoneal dissemination or serosal invasion (first surgery group) and on 5 recurrent gastric cancer patients with ascitic retention (recurrent cancer group), and the MMC concentrations was studied in the perfusate and circulating blood. The perfusate contained MMC 10 micrograms/ml at the onset of IPHP, except one recurrent case of 20 micrograms/ml, and IPHP was performed for 120 minutes except in one case given 20 micrograms/ml of MMC. There was little difference in the hepatorenal functions and perfusate temperatures between the first surgery group and the recurrent cancer group. The drug levels were measured by HPLC method with minimal assay levels of 2 ng/ml. Perfusate drug levels in the first surgery group reduced by half at 12 minutes after the start of IPHP, whereas in the recurrent cancer group, they decreased by half about 60 minutes later. Perfusate drug levels in the first surgery group decreased twice as rapidly as in the recurrent cancer group. The area under the curve (AUC) and average drug levels in the first surgery group were 7,900 micrograms.hr/l and 3.3 micrograms/ml, respectively, and those in the recurrent cancer group were 12,620 micrograms.hr/l and 5.3 micrograms/ml, respectively. On the other hand, the drug levels in peripheral blood were almost the same between the two groups. These data suggest that although recurrent gastric cancer is well suited for IPHP because of high AUC, it is worthwhile performing IPHP combined with surgery for gastric cancer with peritoneal seeding, with due consideration for AUC of 7,900 micrograms.hr/l and the average drug level of 3.3 micrograms/ml.

Adult↗

Pharmacokinetic analysis in intraperitoneal hyperthermic chemotherapy of far-advanced gastric cancer patients.

The pharmacokinetics of mitomycin C (MMC) has been evaluated in 10 far-advanced gastric cancer patients by means of an intraperitoneal hyperthermic perfusion (IPHP) using MMC to prevent and/or treat peritoneal dissemination. Further, misonidazole (MIS), which was used as a thermosensitizer, also was evaluated. The IPHP was performed for 120 min right after surgical procedure, using a closed-circuit with an inflow perfusate temperature from 46.3 approximately 47.5 degrees C and an outflow temperature of 44.0 approximately 46.0 degrees C. The MMC level in the perfusate was 10 micrograms/ml at the onset of IPHP and thereafter decreased to 1.7 +/- 0.4 micrograms/ml minutes later. The average AUC (area under the curve) in the perfusate was 3.3 micrograms/ml during the IPHP. The MMC level in the peripheral blood was 0.15 +/- 0.04 micrograms/ml 30 min after start of the IPHP and increased to 0.18 +/- 0.05 micrograms/ml at the end of IPHP. Additionally, the MIS level in the peripheral blood was 64.7 +/- 10.3 micrograms/ml 60 min after the IPHP, 60.6 +/- 9.2 micrograms/ml at 120 min, and then decreased to 32.8 +/- 10.3 micrograms/ml at 12 hours after IPHP. The AUC was calculated as being 975 micrograms.hr/ml. Again, the level in the portal vein blood was calculated from the peritoneal permeability and the peripheral blood level of the drug. From data, it was concluded that the perfusate and portal vein blood level of MMC, the peripheral blood level of MIS, as well as the perfusate temperature, are important in providing a favorable, safe, antitumoral treatment.

Adult↗

[Clinical evaluation of intraperitoneal hyperthermic perfusion in far-advanced gastric cancer].

Nineteen far-advanced gastric cancer patients, including peritoneal dissemination, underwent surgical treatment followed by intraperitoneal hyperthermic perfusion (IPHP). Seven of them had cancerous ascites, 5 had ovarial metastasis, and in 7 the primary tumor extended to the adjacent organs. Postoperatively, ascitic effusion was absent after IPHP, and all patients were discharged. The survival of the IPHP group was compared with that of 27 advanced gastric cancer patients with serosal invasion (control group), who underwent gastrectomy without IPHP. In the IPHP group, the average and 50% survival was 400 and 520 days, respectively, and 1-year survival rate was 73.3%, against 273 days, 250 days, and 31.8%, respectively, in controls. The survival rate for the IPHP group was statistically better than that of the control group (p less than 0.01). In patients with peritoneal dissemination, the average survival and 50% survival for the IPHP group was 396 and 380 days, respectively, and 1-year survival rate was 62.5%, against 204 days, 170 days, and 16.6%, respectively, in controls. Based on these results, IPHP was suggested to be effective for gastric cancer with serosal invasion, especially with peritoneal dissemination.

Adult↗

[Effect of degradable starch microspheres (DSM) on hepatic hemodynamics].

The effect of intra-arterial infusion of degradable starch microspheres (DSM) on hepatic arterial blood flow was measured using a transit-time ultrasonic blood flow meter. Before the infusion of DSM, the mean hepatic arterial flows were 316 +/- 79 ml/min. After infusion, the mean flows decreased to 43 +/- 86 ml/min (86%). RI-angiography using 99mTc-macroaggregated albumin (MAA) was performed to measure hemodynamic changes in the liver. T/N ratio of 99mTc-MAA accumulation was increased from 0.37 to 0.62. Based on the peripheral MMC blood levels after combined infusion with DSM and MMC, the mean AUC with MMC plus DSM was decreased to 55% of that of AUC with MMC alone. These results show that combined use of DSM is effective for intra-arterial chemotherapy against the hepatic cancer.

Hemodynamics↗

Combined treatment with surgery and intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastrointestinal cancer with peritoneal seeding.

In 19 patients with advanced gastric carcinoma intraperitoneal hyperthermia combined with mitomycin C was administered. After this therapy in repeated cytological examinations of the peritoneal effusion malignant cells could be determined. From 19 patients 5 died innert the first 10 months. The other patients lived 12 months without recurrence.

Chemotherapy, Cancer, Regional Perfusion↗

[Polarographic analysis of tumor tissue oxygen tension after hyperthermia combined with misonidazole].

For the purpose to analyse the influence of a thermosensitizing drug, misonidazole (MIS), on tissue oxygen tension (TpO2), TpO2 in human gastric cancer tissue (H-23) was measured by a polarographic method. MIS, 500 mg/kg, was given i.p. and then the heat treatment was done in a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. A second treatment was performed to develop thermotolerance at the following intervals: 24 hours, 72 hours, 5 days, and 7 days. Tumor doubling time was shortest at 72-hour interval, i.e., the maximal thermotolerance of the tumor developed at 72-hour interval, whereas the tumor doubling time in case of combined use of MIS was shortest at 24-hour interval. TpO2 in the 72-hour interval treatment decreased soon after hyperthermia, and returned to a pre-heated value 3 hours after, whereas in the other 3 treatments the recovery time was 6 to 12 hours. On the other hand, in 24-hour interval of the combined use of MIS, the post-thermal value of TpO2 was about a half of the pre-thermal value and recovered 24 hours after. In the 5- and 7-day interval treatments, TpO2 declined notably and did not return to the pre-thermal value during 24 hours. These data suggest that the thermo-sensitizing effects of MIS were brought about by prolonged and extreme decrease in TpO2.

Adaptation, Physiological↗

Identification of senecionine and senecionine N-oxide as antifertility constituents in Senecio vulgaris.

The MeOH extract of Senecio vulgaris L., administered po to rats on Days 1-10 postcoitum, significantly decreased the number of normal fetuses per pregnant rat found at autopsy on Day 16. Additional experiments showed a similar activity for its hepatotoxic constituents senecionine and senecionine N-oxide, suggesting that the latter two compounds were probably responsible for the effect seen with the extract. No antifertility effects were seen in MeOH extract-treated hamsters.

Animals↗

[The relationship between thermotolerance and the tissue oxygen tension in human gastric cancer tissue].

To study the relationship between thermotolerance and post-thermal phenomenon, tumor pO2 (TpO2) in xenoplanted gastric cancer tissue (H-23) has been measured by a polarographic method. The heat treatment was done in a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. In order to produce thermotolerance, the second treatment was carried out at an interval of 24 hours, or, alternatively at 72 hours, or at 5 days or at 7 days. The thermotolerance of the H-23 tumor reached its maximum at the 72 hour-interval and was seen to disappear completely at 7 days. The TpO2 in the H-23 tumor decreased immediately after a single heat treatment and returned to its pre-treated value after 10 hours. In cases of the second heat treatment, the 72-hour interval group returned to its pre-treated value in 2-6 hours, whereas the 24-hour, 5-day, and 7-day interval groups showed a longer recovery time. The relationship between thermotolerance and TpO2 recovery was inverse at r = -0.858 and p = 0.035. Thus, our study suggests that not only is the thermotolerance affected by the alteration of the intra-cellular components, but also by the post-thermal changes in the tumor vessels.

Animals↗