Takashi Irie

Cervical Ureaplasma urealyticum colonization might be associated with increased incidence of preterm delivery in pregnant women without prophlogistic microorganisms on routine examination.

Aim: We examined whether the detection of Ureaplasma urealyticum DNA in the cervix is associated with preterm labor and delivery.

Significance of cytoreductive surgery including bowel resection for patients with advanced ovarian cancer.

The aim of this study was to determine the significance of bowel resection in advanced ovarian cancer. A total of 64 women with stage IIIc or IV epithelial ovarian cancer, who consecutively received primary treatment between 1991 and 1995, were entered in this prospective study. The outcome of the patients undergoing bowel resection was evaluated. Thirty-nine patients underwent cytoreductive surgery at initial surgery. Of them, 16 patients could undergo optimal operation without bowel resection. Twenty-three patients received bowel resection at initial surgery. Of these 23 patients, 16 underwent optimal operation and 7 did not. Among 25 patients judged as inoperable cases at initial surgery, 21 responded to chemotherapy and underwent second surgery. Of 21 patients receiving second surgery, 15 underwent optimal operation (7 without bowel resection and 8 with bowel resection). The 3-year survival rate for 24 patients undergoing optimal operation with bowel resection (46.8%) was not significantly different from that for 23 patients without bowel resection (59.1%). Postoperative complications were seen in 8 patients (21.6%) of the patients receiving bowel resection and 3 (13.0%) of those without bowel resection. Cytoreductive surgery including bowel resection is effective for an improvement of the survival in patients with advanced ovarian cancer, if an optimal operation can be performed.

A newly developed adenovirus-mediated transfer of a wild-type p53 gene increases sensitivity to cis-diamminedichloroplatinum (II) in p53-deleted ovarian cancer cells

A new recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) was developed and the combination effect of p53 gene transfer and cis-diamminedichloroplatinum (II) (CDDP) was examined in an ovarian cancer cell line, SK-OV-3, with deletion of the p53 gene. AxCAp53 showed a high efficiency of gene transduction and increased sensitivity to CDDP in the SK-OV-3 cells. It was found that the sensitivity of the cells to CDDP correlated with the amount of infectious units of virus per cell of AxCAp53 which correlated with p53 protein expression. The results suggest that the combination of CDDP and AxCAp53 may be a potential strategy for the therapy of CDDP-resistant ovarian cancer.

Radical surgery following neoadjuvant chemotherapy for patients with stage IIIB cervical cancer

AbstractBackground: We conducted a phase II trial of radical surgery following neoadjuvant chemotherapy in patients with stage IIIB cervical cancer. Methods: A total of 26 patients with stage IIIB cervical cancer were entered in this study. Patients were treated with a chemotherapeutic regimen consisting of intraarterial infusion of cisplatin and intravenous infusion of other anticancer agents, to a maximum of 3 courses. If the results of the evaluation indicated that surgery was feasible, radical surgery, including complete removal of pelvic vessels, partial resection of adjacent organs, and pelvic and paraaortic lymphadenectomy, was performed. Patients whose tumors showed no response received radiotherapy. We evaluated operability, survival rate, toxicities, and complications. Additionally, we examined prognostic variables by multivariate analysis in the patients treated by radical surgery. Results: Eighteen patients (69.2%) underwent radical surgery. The remaining eight patients received radiation therapy. The 3-year disease-free survival rate was 72.2% in patients who received surgery and 25.0% in those who received radiotherapy. Multivariate analysis did not show any independent prognostic factors in the patients who underwent surgery. Conclusion: Radical surgery following neoadjuvant chemotherapy may be feasible in two thirds of patients with stage IIIB cervical cancer; therefore, phase III trials can be recommended.

Residual disease and presence of human papillomavirus after conization

The objective of this study was to evaluate the incidence of residual disease and the presence of human papillomavirus (HPV) after conization. Data on 53 patients with carcinoma in situ or microinvasive carcinoma who underwent hysterectomy less than 2 months after conization were examined. Seven of 53 patients (13%) had positive margins. In 4 of these 7 patients (57%), residual disease was found in the postconization hysterectomy specimen. Two of 46 patients (4%) with negative margins also had residual disease. HPV DNA was detected by PCR in 27 of 53 conization specimens and in 2 postconization hysterectomy specimens. Of 2 patients, 1 did not have residual disease. Residual disease could be present even with a negative conization margin, and HPV DNA may be found in a histologically normal cervix after conization.

Enhanced Topoisomerase I Activity and Increased Topoisomerase IIα Content in Cisplatin-resistant Cancer Cell Lines

Although the combined effects of cisplatin (CDDP) and DNA topoisomerase (Topo) inhibitors have been described in recent literature, little is known about the combined effects and their biological basis in CDDP‐resistant cells. The aim of the present study was to elucidate the combined effect of CDDP and Topo inhibitors on CDDP‐resistant cells as well as to investigate the biological factors involved in the sensitivity to these anti‐cancer agents. We found synergistic actions between CDDP and SN‐38 (a Topo I inhibitor) or VP‐16 (a Topo II inhibitor) in KFr cells, a CDDP‐resistant subline of the KF epithelial ovarian carcinoma cell line, but not in the parent KF cells. We subsequently assayed Topo protein levels and enzymatic activities in two sets of CDDP‐sensitive and ‐resistant cell lines: KF and KFr, and HeLa and HeLa/CDDP. The levels of Topo I protein in the CDDP‐resistant cells did not differ from those of their parent cell lines and were unaffected by exposure to CDDP. Topo I enzymatic activity, however, was 2‐ to 4‐fold higher in the CDDP‐resistant cell lines than in their respective parent cell lines. In contrast, higher levels of Topo lice protein were observed both before and after CDDP exposure in the CDDP‐resistant cells than in their controls. However, no difference in Topo II catalytic activity was observed between the CDDP‐resistant and ‐sensitive cells.

Timing of G-CSF administration based on the circadian rhythm in patients with ovarian cancer.

The aim of this study was to determine the relationship between the timing of granulocyte colony-stimulating factor (G-CSF) administration and its efficacy in patients with chemotherapy-induced granulocytopenia. Twenty patients in whom chemotherapy-induced leukopenia developed after the first course were enrolled in this prospective study. Subjects were randomly divided in two groups according to G-CSF injection time as follows: at 7:00 am and 7:00 pm. Before the G-CSF injection, the plasma G-CSF level for all patients was significantly lower at 7:00 am than that at 7:00 pm. After the injection, plasma G-CSF level did not differ between the two groups. The nadir of the leukocyte was 2,554 ± 379/mm3 (granulocyte 1,530 ± 689) for the group injected at 7:00 am, and 2,300 ± 426/mm3 (granulocyte 1,203 ± 848) for the group injected at 7:00 pm. The duration of leukocytes less than 2,000/mm3 and granulocytes less than 1,000/mm3 were 2.8 ± 1.8 days and 3.2 ± 1.8 days, respectively. Those differences were not significant. The present study showed the circadian rhythm of G-CSF levels in patients with ovarian cancer with chemotherapy-induced granulocytopenia, but there was no remarkable difference depending on administration time.

Alteration of a p53 gene status affects outcome of patients with recurrent ovarian cancer.

The aim of this longitudinal study was to examine whether and how the p53 gene is altered in patients with recurrent ovarian cancer and to determine the significance of p53 mutation in recurrent tumors. The primary and recurrent tumors were examined in 15 patients who had recurrent epithelial ovarian cancer, and whose primary tumor contained a wild-type p53 gene. The interval between cytoreductive surgery and the appearance of recurrence ranged from 5.2 to 63.6 months (mean 23.4 months). Mutations in the p53 gene were screened by polymerase chain reaction single strand conformation polymorphism analysis and determined by cycle sequencing. Mutation of the p53 gene in the recurrent tumor was found in 7 of the 15 patients (46.7%). Estimated 3- and 5-year survival rates were 57.1 and 0%, respectively, for patients with p53 gene mutation detected in the recurrence tumor, and 75.0% and 37.5% for patients without the mutation (p = 0.0155). The interval between cytoreductive surgery and the appearance of recurrence did not differ between those groups (549.7 ± 102.2 vs. 832.9 ± 283.8 days). Mean survival time after recurrence was significantly better in the patients without mutation (438.6 ± 56.4 vs. 873.0 ± 157.5 days, p = 0.0125). The present study suggests that p53 gene mutation frequently occurs in recurrent ovarian cancer and that alteration of p53 gene status affects salvage chemotherapy. This phenomenon affects the prognosis of recurrent disease and may predict outcome.

Clinical Responses and Platinum Concentrations in Tumors after Intra-Arterial and Intravenous Administration of Cisplatin in the Same Patients with Cervical Cancer

We evaluated 3 patients with advanced cervical cancer treated with cisplatin intra-arterially and intravenously. The dose of cisplatin was 50 mg/m2 in each infusion. Chemotherapy was repeated at 4-week intervals for three to four courses. The clinical response and the tumor concentration of platinum were evaluated in each course. All patients who received the intra-arterial infusion of cisplatin were judged to be responders, whereas none of them responded to the intravenous infusion. The platinum concentration in tumor tissue was significantly higher after intra-arterial infusion of cisplatin (1.97 +/- 0.04 vs. 2.86 +/- 0.10 microg/g). Although there were no apparent differences in side effects between intra-arterial and intravenous routes, 2 of 3 patients rejected an intra-arterial route. The present study suggests that intra-arterial administration of cisplatin may be useful in treating locally advanced cervical cancer.