Kiyomi Suzuka

Serum vascular endothelial growth factor (VEGF) and VEGF-C levels as tumor markers in patients with cervical carcinoma

Vascular endothelial growth factor (VEGF) and VEGF‐C play a crucial role in the regulation of tumor growth and metastasis. The current study examined the significance of serum VEGF and VEGF‐C levels in relation to conventional clinicopathologic parameters, response to treatment, and survival in patients with cervical carcinoma.

Adjuvant hysterectomy in low-risk gestational trophoblastic disease.

Objective To evaluate the efficacy of adjuvant hysterectomy with chemotherapy for women with low-risk gestational trophoblastic disease. Methods One hundred fifteen consecutive Japanese women (16–52 years old) with low-risk gestational trophoblastic disease (46 with metastatic disease and 69 without) were treated initially with single-agent chemotherapy (etoposide in 85, methotrexate in 27, and actinomycin D in three) with or without adjuvant hysterectomy, and 97 patients (84.3%) achieved primary remission with those treatments. Eight women (9.4%) treated with etoposide required other regimens because of drug resistance or toxicities. The total dose of etoposide given to achieve primary remission was analyzed in 77 women who received etoposide alone or with adjuvant hysterectomy. Results In 34 women with metastatic disease, the mean (± standard deviation [SD]) total dose of etoposide was not significantly different with and without adjuvant hysterectomy (2857 ± 842 mg versus 2815 ± 815 mg; P = .957; Mann-Whitney U test). However, in 43 women without metastases, the total dose of etoposide was significantly less in those who had adjuvant hysterectomies than in those who did not (1750 ± 635 mg versus 2545 ± 938 mg; P < .05; Mann-Whitney U test). Conclusion Adjuvant hysterectomy decreased the total dose of etoposide given to achieve primary remission in women with nonmetastatic, low-risk gestational trophoblastic disease. If the lesions of gestational trophoblastic disease are confined to the uterus and the woman has no desire to preserve fertility, she should be informed of adjuvant hysterectomy as a treatment option.

Detection of epidermal growth factor receptor mRNA in peripheral blood of cervical cancer patients

OBJECTIVE Epidermal growth factor receptor (EGFR) has been reported to be expressed by immunohistochemistry in invasive cervical cancers. We evaluated the feasibility of detecting EGFR mRNA by EGFR-based reverse transcription polymerase chain reaction (RT-PCR) in peripheral blood of patients with cervical cancer. METHODS Expression of EGFR mRNA, cytokeratin (CK)-19 mRNA, and CK-20 mRNA was examined by RT-PCR in 12 human cervical cancer cell lines. All 12 cell lines expressed both EGFR mRNA and CK-19 mRNA, but only 4 of 12 (33.3%) cell lines expressed CK-20 mRNA. Peripheral blood samples from 20 healthy donors and 45 cervical cancer patients were also examined. RESULTS In peripheral blood from 20 healthy donors, neither EGFR mRNA nor CK-20 mRNA was expressed, but CK-19 mRNA was expressed in 13 of 20 (65%). In contrast, EGFR mRNA was expressed in 12 of 45 (26.7%) patients with cervical cancer (P = 0.0071, 2 test, patient vs control). On the other hand, expression of EGFR was observed in 98% of tumor tissues by immunohistochemistry. CK-19 mRNA and CK-20 mRNA were found in 35 of 45 (77.8%) and 0 of 45 (0%) patients, respectively (NS, chi(2) test, patient vs control). The rate of detection of EGFR mRNA in peripheral blood correlated with FIGO stage (P = 0.049). CONCLUSION Both CK-19 mRNA and CK-20 mRNA showed no diagnostic value as markers of circulating tumor cells in cervical cancers. However, EGFR mRNA in blood might be a useful marker of circulating tumor cells in cervical cancers.

Salvage combination chemotherapy with 5-fluorouracil and actinomycin D for patients with refractory, high-risk gestational trophoblastic tumors.

The objective of this study was to evaluate the efficacy and toxicity of a high‐dose 5‐fluorouracil and actinomycin D regimen (the FA regimen) as salvage chemotherapy for patients with high‐risk gestational trophoblastic tumors (GTTs).

Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor

Abstract Objective This study analyzed the outcome of the first pregnancy following chemotherapy for gestational trophoblastic tumor (GTT). Methods A total of 387 patients with GTT (85 patients with high-risk GTT and 302 patients with low-risk GTT) underwent chemotherapy at Chiba University Hospital between 1974 and 2000. Of these patients, 130 women (18 with high-risk GTT and 112 with low-risk GTT), who achieved remission and had at least one conception following chemotherapy, were included in the study. Results The outcomes of all the first subsequent pregnancies in women treated with methotrexate, actinomycin-D, or etoposide (including those switched to other regimens), or combination therapy, were comparable to those in the Japanese general population. However, the incidence of abnormal pregnancies (spontaneous abortion, still birth, repeat mole) was significantly higher in women who conceived within 6 months of completing chemotherapy (4/15; 40%) than in those who conceived after the recommended waiting period of more than 12 months (10/95; 10.5%) ( P = 0.028). Conclusion Patients with GTT who achieved remission after chemotherapy with methotrexate, actinomycin-D, or etoposide, or combination therapy, may anticipate a normal future reproductive outcome. As pregnancies occurring within 6 months following remission are at risk of abnormalities, a waiting period of at least 6 months after chemotherapy for GTT is suggested.

Scalp metastasis of a serous ovarian cancer

Aggressive cytoreductive surgery and cisplatin-containing combination chemotherapy for ovarian cancer have certainly led to longer disease-free survival, while the incidence of distant metastasis is increasing (1,2). We report a case of serous ovarian cancer with FIGO Stage 2C, which suddenly recurred in the scalp without lung metastases and widespread intraperitoneal involvement at 29 months after primary surgery.

Cytologic features of functioning stromal cells in a yolk sac tumor of the ovary. A case report.

BACKGROUND Functioning stromal cells are sometimes seen in primary and metastatic ovarian neoplasms. However, the cytologic features of functioning stromal cells have been described only rarely. CASE A 19-year-old woman had an alpha-fetoprotein-producing ovarian yolk sac tumor with functioning stroma. Her preoperative serum testosterone level was elevated. Imprint cytology showed that the functioning stromal cells had centrally located nuclei with low nuclear/cytoplasmic ratios. Occasionally these cells had vacuolated cytoplasm, suggesting the presence of lipids. In sharp contrast, the yolk sac tumor cells had more pleomorphic and hyperchromatic nuclei. We were able to distinguish between neoplastic and functioning stromal cells on the basis of these findings. In addition, immunostaining for inhibin on imprint cytologic slides was of great help in identifying functioning stromal cells. CONCLUSION Because functioning stromal cells may unexpectedly induce hormonal effects in a variety of ovarian tumors, it is important to identify such cells in cytologic specimens.

Phase I study of daily cisplatin and concurrent radiotherapy in patients with cervical carcinoma

5103 Background: Chemoradiation based on cisplatin is the standard treatment of locally advanced cervical carcinoma; however, the optimal scheduling, dosing were not still decision, the purpose of this study was to determine the maximum-tolerated dose (MTD) of cisplatin when administrated daily during pelvic radiation (RT). METHODS Patients with locally advanced cervical carcinoma and patients who required postoperative RT were registered. Low dose cisplatin (starting dose 6.0mg/m2, 0.5mg/m2 escalation per level) was given with daily application concurrently with RT (2Gy/ day; total dose of 50Gy). Cohorts of three patients were enrolled at each level. If one of three patients at any level developed dose-limiting toxicity (DLT), three additional patients were then treated at the same dose level. DLT was defined as grade 3/4 nonhematologic toxicity except for alopecia, nausea and vomiting, grade 3/4 neutropenia or thrombocytopenia. Cisplatin was interrupted when hematological DLT were observed.The MTD was defined as the dose level below that which produced DLT in more than one-third of treated patients. RESULTS Twenty-five patients were eligible in this study. In 21/25 patients (84%), cisplatin was administrated continuously as planned with no interruption. As shown in the table, the MTD was 8mg/m2 and the DLT was neutropenia. Fourteen patients were analysis for response: 11 complete response and 2 partial responses were obtained with an overall response rate of 92.9%. CONCLUSIONS A dose of 8 mg/m2 daily was determined to be MTD and considered the recommended dose of daily cisplatin. Daily cisplatin is a well-tolerated and effective radiosensitizer in cervical carcinoma patients. [Figure: see text] No significant financial relationships to disclose.

Hydatidiform mole coexistent with a twin live fetus: a national collaborative study in Japan

A national collaborative study was conducted in Japan to evaluate the clinical course and the sequelae of patients with hydatidiform mole coexistent with twin live fetus (HMTF). Seventy-two cases of HMTF were diagnosed based on gross appearance and histopathological criteria. In 18 cases, the molar parts were cytogenetically confirmed to be of androgenetic origin (complete mole). The overall incidence of persistent trophoblastic tumour (PTT) in patients with HMTF was 30.6%, and it increased to 50.0% in the 18 patients with proven androgenetic complete mole coexistent with twin live fetus (CHMTF). Among these patients, the mean gestational age at termination of pregnancy or delivery in those who developed PTT (n = 9) and those who did not (n = 9) were 20.6 and 19.4 weeks respectively. The incidence of severe maternal complications was significantly higher in patients who subsequently developed PTT (P < 0.05). The rate of subsequent development of PTT in patients with CHMTF was found to be considerably higher than in a previous study of patients with single complete mole (50 and 12.5% respectively). However, since the risk of malignancy is unchanged with advancement of gestational age, continued pregnancy may be allowed in patients with HMTF provided that severe maternal complications are controlled and fetal karyotype and development are normal.

Surgical intervention and complications for low-risk gestational trophoblastic tumor

Study Methods: 72 patients with HMTF were diagnosed by macroscopic and histopathologic criteria in Japan. In 18 patients, molar parts were cytogenetically confirmed to be an androgenetic origin (complete mole). Results: The development of persistent trophoblastic tumor (PrT) in patients with HMTF was 30.6%, and it raised to 50.0% in patients with androgenetic complete mole coexistent with a twin live fetus. The mean terminated gestational age in these 18 patients with developing PTT and without developing mT was 20.6 weeks and 19.4 weeks, respectively. Severe maternal complications were accompanied significantly higher in patients subsequently developed PTT. Conclusions: The development of subsequent PTT in patients with HMTF was significantly higher than that of single complete mole. However, since the potential for malignancy was unchanged with advancing gestational age, it may be allowed to continue pregnancy when severe maternal complications are not accompanied and fetal karyotype and development are normal.