Koji Yamazawa

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.

Placental mesenchymal dysplasia initially diagnosed as partial mole.

Placental mesenchymal dysplasia is a rare condition of pregnancy that presents as macroscopic features of molar change in the placenta and normal karyotype fetus. These cases are often misdiagnosed as partial mole. We report a new case of mesenchymal dysplasia. A 27‐year‐old Japanese primigravida delivered an 820 g female baby (46XX karyotype) without congenital anomalies at 27 weeks gestation due to massive bleeding with placenta previa. The placenta had mimicking partial moles, grape‐like vesicles and normal villi that diffusely occupied the area on the maternal surface of the placenta. Pathologically, enlarged stem villi contained loose, moderately cellular connective tissue with focal cistern‐like formation, and peripherally located vessels. Abnormal trophoblastic proliferation and trophoblastic inclusions were not observed in any of the sections examined. Some villi contained chorioangiomatoid changes. The mother and child were followed up for more than 5 years and showed no sign of trophoblastic disease or Beckwith–Wiedemann syndrome features.

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.

A case-control study of endometrial cancer after antipsychotics exposure in premenopausal women.

Objective: Most endometrial cancers are related to hormonal imbalance, and antipsychotics are a common cause of hyperprolactinemia. We investigated the possible relation between the use of antipsychotics and the risk of endometrial cancer. Methods: A case-control study was conducted on premenopausal women at the Chiba University Hospital between 1989 and 2000. The cases were 41 patients with histologically confirmed endometrial cancer. For each case, there were 3 controls matched by age and date of visit. Subsequently 123 women without endometrial cancer were enrolled as controls. Detailed information including obesity, parity, hypertension, diabetes mellitus, use of exogenous estrogen and use of antipsychotics was analyzed. Odds ratios, two-sided p values and 95% confidence intervals were estimated by a conditional logistic regression analysis. Radioimmunoassays of serum luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol and progesterone were performed in 4 of 5 patients with endometrial cancer who were using antipsychotics. Results: Use of antipsychotics, diabetes mellitus and obesity were identified as independent variables with risk estimates of 5.4, 9.3 and 4.9, respectively. Serum progesterone, estradiol and prolactin levels ranged from 0.4 to 0.7 ng/ml, 32 to 110 pg/ml and 34 to 258 ng/ml, respectively. Conclusions: Use of antipsychotics is a risk factor for endometrial cancer, and hyperprolactinemia associated with antipsychotics may impart the risk of endometrial cancer in premenopausal women.

Life-threatening Clostridium difficile-associated diarrhea induced by paclitaxel-carboplatin combination chemotherapy.

Diarrhea has been reported in 10% of patients undergoing antineoplastic chemotherapy (1). Infectious colitis contributes to diarrhea in some chemotherapy-induced cases, and the most common etiologic agent is Clostridium difficile. Prior antibiotic use is considered the most important risk factor in the development of C. difficile-associated diarrhea (CDAD). However, CDAD can occur in the absence of antibiotic use and the association between antineoplastic therapy and CDAD has recently become evident. Meanwhile, the risk of paclitaxel in CDAD is not well defined.

Early growth response-1 mediates downregulation of telomerase in cervical cancer

Early growth response (Egr)‐1 is a transcription factor that triggers transcription of downstream genes within 15–30 min of various stimulations. These genes are expressed rapidly through specific promoter activation and mediate cell growth and angiogenesis. Following the previous computational identification of a site that was thought to be an Egr‐1 consensus binding site at –273 to –281 in the human telomerase reverse transcriptase (hTERT) promoter region, the present study was conducted to evaluate the role of Egr‐1 in the regulation of hTERT and telomerase in uterine cervical cancer. First, the expression of Egr‐1 and hTERT at the mRNA level was examined in cervical cancer tissues. Egr‐1 and hTERT were expressed much higher in cervical cancer tissues than in the normal cervix. However, a negative correlation was noted in the expression between Egr‐1 and hTERT. By luciferase assay using hTERT promoter constructs, hTERT transcriptional activation was shown to be inhibited when Egr‐1 was overexpressed. Furthermore, Egr‐1 overexpression decreased hTERT protein production as well as hTERT mRNA as observed by western blotting analysis and real‐time reverse transcription–polymerase chain reaction, respectively. The present study suggests that Egr‐1 plays an important regulatory role in the transcriptional activation of hTERT. (Cancer Sci 2008; 99: 1401–1406)

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).

Discordance between serum level and tissue immunohistochemical staining of CA125 in endometrioid adenocarcinoma of the uterine corpus.

This study was designed to correlate tissue expression of CA125 with the corresponding serum value in endometrial cancer. The records of 52 endometrioid adenocarcinomas diagnosed were reviewed. Serum CA125 levels were examined before definitive surgery, and 20 U/ml was used as the cutoff value. Immunohistochemical staining for CA125 was assessed according to the ImmunoReactive Score. Statistical analyzes were performed to identify independent factor for high serum CA125 levels, including CA125 staining and the conventional pathologic features. Elevated serum CA125 levels were found in 15 of 52 patients (29%) (range, 0.1-172.1; mean 22.6 U/ml). The frequency of positive CA125 tissue staining (35/52, 67%) tended to be higher than that of elevated serum levels (p = 0.046). Fifteen patients with elevated serum CA125 levels statistically differed from the remaining 37 patients with normal serum CA125 level with respect to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.027) and lymph node metastasis (p = 0.024), and tended to have positive washing cytology (p = 0.052). In multivariate analysis, elevated serum CA125 significantly correlated only with FIGO stage III, but not with tumor size or CA125 tissue staining. Intrauterine tumor may not be the main source of serum CA125 in endometrial cancer, and elevated serum level is closely related to the presence of disseminated cancer cells in the peritoneal cavity.

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.

Sebaceous carcinoma of the uterine cervix: a case report.

Sebaceous carcinoma is an uncommon neoplasm that usually arises in the head and neck region. A few cases of sebaceous carcinoma of the female genital tract have been reported, most of which arose in the vulva. We report the first case of sebaceous carcinoma of the uterine cervix. A 25-year-old, nulligravida woman presented with genital bleeding; there was a history of systemic lupus erythematosus but not Fordyces disease. A 3.8-cm exophytic lesion on the cervix was biopsied and staged FIGO stage IB1. A radical hysterectomy was performed. On pathological examination, the tumor replaced the entire cervix and extended into the left parametrium and posterior vaginal fornix. On microscopic examination, the tumor was a sebaceous carcinoma, similar to those described in other sites. Postoperative radiotherapy was administered, but the patient died of tumor 8 months postoperatively.