Minoru Watanabe

Heparanase expression and angiogenesis in endometrial cancer.

Human heparanase has been shown to function in tumor progression, metastatic spread, and tumor angiogenesis. The aim of the present study was to assess heparanase expression in endometrial cancer in correlation with neovascularization and clinicopathological factors. Forty endometrial cancers were obtained from previously untreated patients (median age 55.5, range 33–78 years). The expression of heparanase mRNA was evaluated using a semiquantitative reverse transcriptase-polymerase chain reaction. Tumor angiogenesis was assessed using microvessel counting. The Mann-Whitney U test, one-factor ANOVA test, and Spearman’s test were used to determine the relationship between heparanase expression, microvessel density, and clinicopathological parameters. The expression of heparanase mRNA was detected in 20 of 40 (50%) endometrial cancers, and was significantly correlated with FIGO stage IIIc (p = 0.0075), the presence of lymph-vascular space involvement (p = 0.0041), lymph node metastasis (p = 0.0049), and histological tumor grade (p = 0.0030). Microvessel density was also associated with FIGO stage IIIc (p = 0.027), the presence of lymph-vascular space involvement (p = 0.001), lymph node metastasis (p = 0.038), ovarian metastasis (p = 0.030) and histological tumor grade (p = 0.0030). Moreover, we found a strong positive correlation between heparanase expression and microvessel density (r2 = 0.475, p = 0.0001). These results suggest that the expression of heparanase may influence different malignant behaviors in endometrial cancer.

Stage Ia1 cervical squamous cell carcinoma: conservative management after laser conization with positive margins

OBJECTIVE Cone margin status has been reported to be the most important predictor of recurrent disease in patients with cervical intraepithelial neoplasia (CIN) undergoing cervical conization. Our purpose was to evaluate the conservative management of selected patients with microinvasive (FIGO stage Ia1) squamous cell carcinoma who have been treated by cervical conization with positive margins. METHODS Twenty-seven patients underwent KTP laser conization and vaporization for stage Ia1 squamous cell carcinoma followed by careful observation. Involved margins were diagnosed if CIN III or more was present at the ectocervical or endocervical margin and 7 patients formed the basis of the present study. Follow-up consisted of cytology, histology, and pelvic examination. Disease recurrence was defined as a histology diagnosis of CIN III or more on colposcopically directed biopsy or endocervical curettage. RESULTS The endocervical margins were involved by carcinoma in situ in seven (26%) patients. No ectocervical margin involvement was detected. No lymph-vascular space involvement (LVSI) and confluent invasion were seen. All seven patients were free of recurrent disease during median follow-up of 4.0 (range 2.3-7.6) years. CONCLUSION These results suggest that laser conization and vaporization may be a reasonable treatment option in patients with microinvasive (FIGO Stage Ia1) squamous cell carcinoma despite positive cone margins without invasive disease when LVSI is not demonstrated.

Prognostic factors and failure pattern in lymph node-negative stage IB and II cervical carcinoma treated with radical hysterectomy and postoperative irradiation.

The aim was to determine the prognostic factors and recurrence pattern in stages IB and II cervical carcinoma patients with negative pelvic lymph nodes. 224 patients with stages IB and II cervical carcinoma underwent radical hysterectomy (RH) from 1982 through 1995. Of 161 patients with negative lymph nodes, 65 patients received postoperative irradiation (RT) and 96 patients were given no further therapy according to surgical pathological findings. The overall 5-year disease-free survival was 94.1%. Two of 96 RH patients (2%) and 10 of 65 RH + RT patients (15%) had recurrence in pelvic and distant sites almost equally. Multivariate analysis revealed deep cervical invasion as the only independent prognostic factor. The 5-year disease-free survival was 98.8% for patients with shallow invasion and 85.8% for patients with deep invasion (p < 0.0001). It is worthwhile to develop new strategies for the lymph node-negative patients with deep stromal invasion.

Analysis of TH1 and TH2 cells by intracellular cytokine detection with flow cytometry in patients with ovarian cancer

Objective: Our aim is to assess the immune status of patients with ovarian cancer by analyzing the ratio of T helper type 1 (TH1) to T helper type 2 (TH2) populations in peripheral blood lymphocytes (PBL). Methods: We examined TH1/TH2 ratios in PBL obtained from 21 ovarian cancer patients who had just received postoperative chemotherapy, by detecting the intracellular IFN-γ and IL-4 production with 3-color flow cytometry. Additionally, we evaluated the influence of a granulocyte-colony stimulating factor (G-CSF) injection on TH1 and TH2 populations for a rescue of granulocytopenia due to the chemotherapy. Results: We could not find any significant difference of the TH1/TH2 ratios in terms of age, International Federation of Gynecology and Obstetrics (FIGO) clinical stage and clinical tumor status. As for the clinical tumor status, however, the patients with residual cancer had a higher TH1/TH2 ratio, though it was not statistically significant (p = 0.15). Anticancer chemotherapy is also considered to lead to the immunosuppressive state of the patients. TH1 and TH2 populations of PBL in the patients during chemotherapy showed an unfavorable imbalance that was shifted from TH1 to TH2 10 days after anticancer drug administration (p = 0.049). G-CSF administration, on the other hand, was likely to induce a cell population shift from TH2 to TH1 assessed by the intracellular cytokine assay (p = 0.051), and never induced an unfavorable imbalance from TH1 to TH2 in the T cell population by a 1-day injection of G-CSF. Conclusion: Together, these data indicate that the TH1/TH2 ratio analyzed by intracellular cytokine flow cytometry seems to be a good indicator to assess the immune status in cancer.

A Study on High Temperature Superconducting Coil of Different Coil Arrangements

As for the stored energy density, the solenoid coil has the larger value. On the other hand, the toroidal field coil has the least leakage flux. The primary concern of HTS SMES coil is the reduction of the cost, while securing superconducting coil performance. For this purpose, the required HTS tape length needs to be as short as possible. The critical current and n values of HTS tapes depends on the magnetic fields as well as its field angle to the tapes. Therefore, the performance of magnets wound with HTS tapes needs to be analyzed based on above factors. The current-voltage characteristics of the HTS coil were analyzed by means of fitting equations of the critical current and n value obtained from the measured values of the Bi2223/Ag tape. The stored energy of four kinds of coil arrangement was analyzed, thereby pursuing the shortest length of HTS tapes. The toroidal coil requires 58% longer HTS tapes than the solenoidal coil to store the energy of 100 kJ, but 0.01 T leakage field region at the mid-plane is about a half of the solenoid coil.

Combination chemotherapy with irinotecan hydrochloride (CPT-11) and mitomycin C in platinum-refractory ovarian cancer.

The aim of this study was to examine the level of activity of irinotecan hydrochloride (CPT-11) and mitomycin-C (MMC) combination chemotherapy in a patient population with platinum-refractory ovarian cancer. Patients received CPT-11 (140 mg/m2) in combination with MMC (7 mg/m2) on days 1, 15, 29 until disease progression, unacceptable toxicity developed, or they elected to discontinue treatment. Overall, 61 cycles of CPT-11/MMC chemotherapy were delivered to 13 patients. The major toxicity with this regimen was neutropenia, which was brief and reversible. The incidences of grade 3 and 4 neutropenia were 46% (6/13) and 15% (2/13), respectively. The nonhematological toxicities were generally mild and well tolerated. Of the 13 patients, 4 (31%) experienced an objective response (1 CR, 3 PRs). Among responders, the median duration of response was 30 weeks (range, 12 to 292+ weeks). The median time to progression for the 13 patients who received treatment on this trial was 24 weeks (range, 8 to 292+ weeks), with a median survival of 36 weeks (range, 20 to 292+ weeks). This preliminary study shows that the combination of CPT-11 and MMC appears to be an active regimen in patients with refractory ovarian cancer.

Docetaxel and carboplatin combination chemotherapy for recurrent endometrial cancer

Abstract. There is no consensus regarding the optimal chemotherapy for endometrial cancer patients, and a need for better chemotherapy is evident. Two individuals with recurrent metastatic endometrial cancer treated with docetaxel and carboplatin combination chemotherapy are presented here. Both cases showed objective response to the chemotherapy (one complete response and the other partial response); response duration was 7 and 18 months, respectively. One patient who achieved complete response is alive without disease for 12 months after recurrence. Adverse effects in this regimen were mild and tolerable. Docetaxel in combination with carboplatin may be active agents for patients with metastatic endometrial cancer.

Survival of patients with advanced ovarian cancer treated with intermittent chemotherapy following cytoreductive surgery and adjuvant chemotherapy

AbstractBackground. The purpose of this study was to report the duration of the progression-free interval (PFI) in advanced ovarian cancer patients who were treated with intermittent maintenance chemotherapy. Methods. Between 1991 and 1998, 25 patients with stage III or IV ovarian cancer were enrolled in a trial of intermittent maintenance chemotherapy. All patients underwent cytoreduction surgery, and received adjuvant chemotherapy, after which they were treated with intermittent maintenance chemotherapy every 3 to 4 months for 2 years. Results. The median PFI in the 25 women in the intermittent chemotherapy group was 25 months, while in the 32 patients in the control group it was 18 months (P = 0.0124). The median survival of women treated with the intermittent chemotherapy was 34 months, and for the control group patients, it was 35 months (P = 0.0672). Multivariate analysis in the intermittent chemotherapy group revealed that the only factor that correlated significantly with PFI was the status after adjuvant chemotherapy (P = 0.0137). In patients with no evidence of disease after the adjuvant chemotherapy, the median survival was 39 months in the intermittent chemotherapy group, and 35 months in the control group (P = 0.0156). The median PFI was 28 months in the intermittent chemotherapy group, and 18 months in the control group (P = 0.0012). Conclusion. It would be warranted to perform intermittent maintenance chemotherapy for patients with advanced ovarian cancer, if a clinically disease-free status could be achieved after completion of the standard treatment procedure.