AIM: To compare the pharmacokinetics and tissue distribution of 5-fluorouracil administered intraperitoneally with two isotonic carrier solutions: HAES-steri (neotype 6% hydroxyethyl starch), a novel carrier solution ...AIM: To compare the pharmacokinetics and tissue distribution of 5-fluorouracil administered intraperitoneally with two isotonic carrier solutions: HAES-steri (neotype 6% hydroxyethyl starch), a novel carrier solution with middle molecular weight and physiologic saline (0.9% sodium chloride solution), a traditional carrier solution for intraperitoneal chemotherapy, in rats. METHODS: A total of 60 Sprague Dawley rats were randomized into groups according to the carrier solution administered. Each group was further randomized according to the intraperitoneal dwell period (1, 3, 6, 12, 18 and 24 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and quantitated. Drug concentrations in peritoneal fluid, plasma, and tissues were determined by high- performance liquid chromatography. RESULTS: The mean volumes remaining in the peritoneal cavity were significantly higher with HAES- steri than those with physiologic saline at 1, 6, 12, 18, and 24 h (P = 0.047, 0.009, 0.005, 0.005 and 0.005 respectively, the percentages of remaining peritoneal fluid volume were 89.9 ± 5.6 vs 83.4 ± 4.9, 79.9 ± 2.8 vs 56.2 ± 15.7, 46.8 ± 5.5 vs 24.7 ± 9.7, 23.0 ± 2.8 vs 0.0 ± 0.0 and 4.2 ± 1.7 vs 0.0 ± 0.0 respectively). Mean concentrations in peritoneal fluid were significantly higher with HAES-steri than those with physiologic saline at 3, 12 and 18 h (P = 0.009, 0.009 and 0.005 respectively, the concentrations were 139.2768 ± 28.2317 mg/L vs mg/L, 11.5427 ± 3.0976 mg/L vs 0.0000 ± 0.0000 mg/L and 4.7724 ± 1.0936 mg/L vs 0.0000 ± 0.0000 mg/L respectively). Mean plasma 5-fluorouracil concentrations in portal vein were significantly higher with HAES-steri at 3, 12, 18 and 24 h (P = 0.009, 0.034, 0.005 and 0.019 respectively, the concentrations were 3.3572 ± 0.8128 mg/L vs 0.8794 ± 0.2394 mg/L, 0.6203 ± 0.9935 mg/L vs 0.0112 ± 0.0250 mg/L, 0.3725 ± 0.3871 mg/L vs 0.0000 ± 0.0000 mg/L, and 0.2469 ± 0.1457 mg/L vs 0.0000 ± 0.0000 mg/L respectively), but significantly lower at 1 h (P = 0.009, the concentrations were 4.1957 ± 0.6952 mg/L vs 7.7406 ± 1.2377 mg/L). There were no significant differences in the plasma 5-fluorouracil in inferior caval vein at each time-point. 5-fluorouracil concentrations were significantly greater with HAES-steri at 18 h in gastric tissue (P = 0.016, the concentrations were 0.9486 ± 0.8173 mg/L vs 030392 ± 0.0316 mg/L), at 18 h in colon (P = 0.009, the concentrations were 0.1730 ± 0.0446 mg/L vs 0.0626 ± 0.0425 mg/L), at 3, 6, 12 and 24 h in liver (P = 0.009, 0.013, 0.034 and 0.013 respectively, the concentrations were 0.6472685 ± 0.5256 mg/L vs 0.1554 ± 0.1043mg/L, 0.8606826 ± 0.7155 mg/L vs 0.0014 ± 0.0029 mg/L, 0.0445 ± 0.0330 mg/L vs 0.0797 ± 0.1005 mg/L and 0.0863 ± 0.0399 mg/L vs 0.0034 ± 0.0075 mg/L respectively) and at 18 h in lung (P = 0.009, the concentrations were 0.0886 ± 0.0668 mg/L vs 0.0094 ± 0.0210 mg/L). There were no differences in 5-fluorouracil concentrations in renal tissue at each time-point. CONCLUSION: The use of intraperitoneal 5-fluoro- uracil with HAES-Steri carrier solution provides a pharmacokinetic advantage for a local-regional killing of residual tumor cells and improve the accumulated penetrability of 5-fluorouracil with decreased systemic toxicity. Further clinical feasibility studies on the use of HAES-steri as carrier solution for intraperitoneal chemotherapy with 5-fluorouracil are warranted.展开更多
Objective: The aim of the study was to evaluate the clinical value of preoperative intra-arterial infusion chemotherapy and embolization in treating the aggressive subtype of endometrial carcinoma with hysterectomy. M...Objective: The aim of the study was to evaluate the clinical value of preoperative intra-arterial infusion chemotherapy and embolization in treating the aggressive subtype of endometrial carcinoma with hysterectomy. Methods: Fifteen cases of endometrial carcinoma were performed intra-arterial chemotherapy and embolization before operation with carboplatin or cisplatin, epirubicin or ADM, and all the cases were performed the arterial chemoembolization with KMG or gel-foam particles mixed with 1/3 total drug dose after 2/3 total drug dose perfusion through the bilateral feeding arteries. Of 15 cases, there were 5 cases with uterine papillary serous carcinoma, 3 cases with endometrial clear cell carcinoma, and 7 cases with endometrial adenosquamous carcinoma. Results: Fifteen cases of endometrial carcinoma were performed operations after 3–4 weeks of intra-arterial chemotherapy and embolization. In these cases, 3 were found mass necrosis and lymphocyte cells infiltration in the tumor tissues but no carcinoma cells, which was noted as histological complete remission (HCR). After intra-arterial chemotherapy and embolization 3–4 weeks, the expression of proliferating cell nuclear antigen (PCNA) was obviously reduced (P < 0.001). Conclusion: The preoperative intra-arterial chemotherapy and embolization can improve the operability of resection in patients with aggressive subtype of endometrial carcinoma, reduce the expression of PCNA, adjust malignancy of endometrial carcinoma, and improve prognosis.展开更多
文摘AIM: To compare the pharmacokinetics and tissue distribution of 5-fluorouracil administered intraperitoneally with two isotonic carrier solutions: HAES-steri (neotype 6% hydroxyethyl starch), a novel carrier solution with middle molecular weight and physiologic saline (0.9% sodium chloride solution), a traditional carrier solution for intraperitoneal chemotherapy, in rats. METHODS: A total of 60 Sprague Dawley rats were randomized into groups according to the carrier solution administered. Each group was further randomized according to the intraperitoneal dwell period (1, 3, 6, 12, 18 and 24 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and quantitated. Drug concentrations in peritoneal fluid, plasma, and tissues were determined by high- performance liquid chromatography. RESULTS: The mean volumes remaining in the peritoneal cavity were significantly higher with HAES- steri than those with physiologic saline at 1, 6, 12, 18, and 24 h (P = 0.047, 0.009, 0.005, 0.005 and 0.005 respectively, the percentages of remaining peritoneal fluid volume were 89.9 ± 5.6 vs 83.4 ± 4.9, 79.9 ± 2.8 vs 56.2 ± 15.7, 46.8 ± 5.5 vs 24.7 ± 9.7, 23.0 ± 2.8 vs 0.0 ± 0.0 and 4.2 ± 1.7 vs 0.0 ± 0.0 respectively). Mean concentrations in peritoneal fluid were significantly higher with HAES-steri than those with physiologic saline at 3, 12 and 18 h (P = 0.009, 0.009 and 0.005 respectively, the concentrations were 139.2768 ± 28.2317 mg/L vs mg/L, 11.5427 ± 3.0976 mg/L vs 0.0000 ± 0.0000 mg/L and 4.7724 ± 1.0936 mg/L vs 0.0000 ± 0.0000 mg/L respectively). Mean plasma 5-fluorouracil concentrations in portal vein were significantly higher with HAES-steri at 3, 12, 18 and 24 h (P = 0.009, 0.034, 0.005 and 0.019 respectively, the concentrations were 3.3572 ± 0.8128 mg/L vs 0.8794 ± 0.2394 mg/L, 0.6203 ± 0.9935 mg/L vs 0.0112 ± 0.0250 mg/L, 0.3725 ± 0.3871 mg/L vs 0.0000 ± 0.0000 mg/L, and 0.2469 ± 0.1457 mg/L vs 0.0000 ± 0.0000 mg/L respectively), but significantly lower at 1 h (P = 0.009, the concentrations were 4.1957 ± 0.6952 mg/L vs 7.7406 ± 1.2377 mg/L). There were no significant differences in the plasma 5-fluorouracil in inferior caval vein at each time-point. 5-fluorouracil concentrations were significantly greater with HAES-steri at 18 h in gastric tissue (P = 0.016, the concentrations were 0.9486 ± 0.8173 mg/L vs 030392 ± 0.0316 mg/L), at 18 h in colon (P = 0.009, the concentrations were 0.1730 ± 0.0446 mg/L vs 0.0626 ± 0.0425 mg/L), at 3, 6, 12 and 24 h in liver (P = 0.009, 0.013, 0.034 and 0.013 respectively, the concentrations were 0.6472685 ± 0.5256 mg/L vs 0.1554 ± 0.1043mg/L, 0.8606826 ± 0.7155 mg/L vs 0.0014 ± 0.0029 mg/L, 0.0445 ± 0.0330 mg/L vs 0.0797 ± 0.1005 mg/L and 0.0863 ± 0.0399 mg/L vs 0.0034 ± 0.0075 mg/L respectively) and at 18 h in lung (P = 0.009, the concentrations were 0.0886 ± 0.0668 mg/L vs 0.0094 ± 0.0210 mg/L). There were no differences in 5-fluorouracil concentrations in renal tissue at each time-point. CONCLUSION: The use of intraperitoneal 5-fluoro- uracil with HAES-Steri carrier solution provides a pharmacokinetic advantage for a local-regional killing of residual tumor cells and improve the accumulated penetrability of 5-fluorouracil with decreased systemic toxicity. Further clinical feasibility studies on the use of HAES-steri as carrier solution for intraperitoneal chemotherapy with 5-fluorouracil are warranted.
文摘Objective: The aim of the study was to evaluate the clinical value of preoperative intra-arterial infusion chemotherapy and embolization in treating the aggressive subtype of endometrial carcinoma with hysterectomy. Methods: Fifteen cases of endometrial carcinoma were performed intra-arterial chemotherapy and embolization before operation with carboplatin or cisplatin, epirubicin or ADM, and all the cases were performed the arterial chemoembolization with KMG or gel-foam particles mixed with 1/3 total drug dose after 2/3 total drug dose perfusion through the bilateral feeding arteries. Of 15 cases, there were 5 cases with uterine papillary serous carcinoma, 3 cases with endometrial clear cell carcinoma, and 7 cases with endometrial adenosquamous carcinoma. Results: Fifteen cases of endometrial carcinoma were performed operations after 3–4 weeks of intra-arterial chemotherapy and embolization. In these cases, 3 were found mass necrosis and lymphocyte cells infiltration in the tumor tissues but no carcinoma cells, which was noted as histological complete remission (HCR). After intra-arterial chemotherapy and embolization 3–4 weeks, the expression of proliferating cell nuclear antigen (PCNA) was obviously reduced (P < 0.001). Conclusion: The preoperative intra-arterial chemotherapy and embolization can improve the operability of resection in patients with aggressive subtype of endometrial carcinoma, reduce the expression of PCNA, adjust malignancy of endometrial carcinoma, and improve prognosis.
