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Objective. To clarify the pharmacological advantage of carboplatin-based intraperitoneal chemotherapy using the three-compartment mathematical model. Methods. Eleven consecutive patients in one institution underwent intraperitoneal administration of carboplatin, and 11 consecutive patients in another institution received intravenous administration. Carboplatin (AUC = 6 mg × min/ml) was diluted in 500 ml 5% glucose and administered either as an intraperitoneal bolus infusion or intravenous drip infusion during 1 h. Patients undergoing intravenous injection also received an infusion of 500 ml 5% glucose to obtain intraperitoneal samples. Intraperitoneal fluid and blood samples were obtained, immediately and 1, 2, 4, 8, 12, and 24 h after administration. The mathematical model consisting of a three-compartment model was applied to analyze the pharmacokinetics. The model was created with simultaneous differential equations and was solved by the Runge–Kutta method. Results. The rate constants of platinum diffusion from the peritoneal cavity to serum, serum to peritoneal cavity, serum to peripheral space, peripheral space to serum, and elimination were 0.94 ± 0.79 (mean ± SD), 1.28 ± 2.50, 16.50 ± 9.26, 0.99 ± 0.62, and 4.14 ± 1.45 (h −1 ), respectively. When the theoretical pharmacological concentration of platinum was calculated using this mathematical model, 24-h platinum AUC in the serum was exactly the same regardless of intraperitoneal or intravenous administration of carboplatin. However, the 24-h platinum AUC in the peritoneal cavity was approximately 17 times higher when carboplatin was administered by the intraperitoneal route. Conclusion. The present pharmacological analysis suggests that intraperitoneal infusion of carboplatin is feasible not only as an intraperitoneal regional therapy but also as a more reasonable route for systemic chemotherapy.

The objective of this study is to clarify the association between the expression of two types angiogenic factors, vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase(dThdPase) and clinicopathological features, including tumor angiogenesis, in cervical cancers.The expression of VEGF and PD-ECGF was evaluated by immunohistochemical staining of tumor specimens from 73 patients with stage Ib-IIb cervical cancer (51, squamous cell carcinoma; 19, adenocarcinoma; 3, adenosquamous carcinoma) who underwent radical hysterectomy. The microvessel density was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area.The microvessel density in adenocarcinomas was significantly higher than that in squamous cell carcinomas (P0.01). The intensity of VEGF expression in adenocarcinomas was significantly stronger than that in squamous cell carcinomas (P0.05). In contrast, the expression of PD-ECGF in squamous cell carcinomas was significantly higher than that in adenocarcinomas (P0.0001) and adenosquamous carcinomas (P0.01). There was an inverse relationship between VEGF expression and PD-ECGF expression among all patients studied (P0.001). The microvessel density was significantly correlated with the intensity of VEGF expression (P0.05). In contrast, there was no correlation between the microvessel density and the expression of PD-ECGF.The expression of VEGF appears to be involved in the promotion of angiogenesis in cervical cancers. Furthermore, we propose that angiogenic pathways may be different in different types of cervical cancers.

It is very rare to find endometrial cancers arising within a short period following childbirth, presumably because pregnancy has a protective effect against endometrial cancer mediated by elevated secretion of progesterone. We present the case of a 30-year-old Japanese woman with stage IIIC endometrial cancer that was found 7 months after childbirth. The patient was treated with surgery followed by 6 cycles of intravenous combination chemotherapy and oral administration of medroxyprogesterone acetate. Histopathological examination of surgical specimen revealed poorly differentiated adenosquamous carcinoma of the endometrium with deep myometrial invasion, cervical stromal involvement, and pelvic and paraaortic lymph node metastases. The disease progressed rapidly and the patient died of the disease.