Guidelines for obstetrical practice in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2014 edition.

The 'Clinical Guidelines for Obstetrical Practice, 2011 edition' were revised and published as a 2014 edition (in Japanese) in April 2014 by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction of burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. The number of Clinical Questions and Answers items increased from 87 in the 2011 edition to 104 in the 2014 edition. The Japanese 2014 version included a Discussion, a List of References, and some Tables and Figures following the Answers to the 104 Clinical Questions; these additional sections covered common problems and questions encountered in obstetrical practice, helping Japanese readers to achieve a comprehensive understanding. Each answer with a recommendation level of A, B or C was prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' was weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 104 Clinical Questions and Answers items, with the omission of the Discussion, List of References, and Tables and Figures, are presented herein to promote a better understanding among English readers of the current standard care practices for pregnant women in Japan.

Early pregnancy outcomes after chemotherapy for gestational trophoblastic tumor.

OBJECTIVE: To analyze the outcome of the first pregnancy following chemotherapy for gestational trophoblastic tumor (GTT). STUDY DESIGN: A total of 393 patients with GTT (87 with high-risk and 306 with low-risk GTT) underwent chemotherapy at Chiba University Hospital between 1974 and 2000. Of them, 137 (19 with high-risk and 118 with low-risk GTT) who achieved primary remission and had at least 1 conception following chemotherapy were included in the study. RESULTS: The overall outcomes of the first subsequent pregnancies in the 137 women treated with chemotherapy were comparable to those in the general Japanese population. However, the incidence of abnormal pregnancies (spontaneous abortion, stillbirth, repeat mole) was significantly higher in women who conceived within 6 months of completing chemotherapy (6 of 16, 37.5%) than in those who conceived after the recommended waiting period, > 12 months (11 of 99, 10.5%) (P=.014). CONCLUSION: Patients who achieved primary remission with various kinds of chemotherapy may anticipate a normal future reproductive outcome. As pregnancies occurring within 6 months following remission are at risk of abnormality, a waiting period of at least 6 months after chemotherapy for GTT is recommended.

Salvage chemotherapy for high-risk gestational trophoblastic tumor.

OBJECTIVE: To evaluate the efficacy and safety of etoposide/methotrexate/actinomycin D (MEA regimen) as initial chemotherapy and 5-fluorouracil/actinomycin D (FA regimen) as salvage chemotherapy for high-risk gestational trophoblastic tumor (GTT). STUDY DESIGN: From 1985 to 2001, 36 patients with World Health Organization (WHO)--defined high-risk GTT were treated with MEA or FA at Chiba University Hospital. Thirty-three patients were initially treated with MEA. FA was administered to 11 patients; 1 had had no previous chemotherapy, 7 had developed drug resistance to MEA, 1 had relapsed following MEA, and 2 had relapsed following etoposide/methotrexate/actinomycin D/ cyclophosphamide/vincristine (EMA/CO) combination chemotherapy. RESULTS: The primary remission rate with MEA was 69.7% (23 of 33). With FA the survival rate was 81.8% (9 of 11) for a mean follow-up period of 11.5 years. Two patients died due to multidrug resistance, and 2 patients relapsed subsequently. The 2 relapse cases were successfully salvaged again with MEA. The toxicity of FA was evaluated in 89 cycles. Myelosuppression seemed to be the dose-limiting toxicity, and the incidence of WHO grade 4 leukocytopenia and thrombocytopenia were 5.6% and 3.4%, respectively. CONCLUSION: Although etoposide-containing chemotherapy is currently the most effective and well tolerated regimen for high-risk GTT, 20-30% of patients develop drug resistance to these regimens. Salvage combination chemotherapy with FA is effective for refractory patients, and the toxicity is predictable and manageable.

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.

Criteria for initiating chemotherapy in patients after evacuation of hydatidiform mole.

OBJECTIVES: To evaluate the spontaneous regression curve of serum human chorionic gonadotropin (hCG) in patients with an uneventful course after evacuation of hydatidiform mole and to compare the criteria for initiating chemotherapy in patients after evacuation of mole. METHODS: From 1986 to 2001, 608 patients were followed at our department after evacuation of mole. The spontaneous regression curves of serum hCG in 432 patients with an uneventful course were established. RESULTS: After evacuation of mole, the titers of serum hCG decreased constantly, and 90% of patients with an uneventful course were within normal range within 16 weeks. In 432 patients with an uneventful course, the upper 95% confidence limit of serum hCG at 5, 8 and 20 weeks was 753.7, 422.9 and 14.8 mIU/ml, respectively. Moreover, 39 (9.0%) and 15 patients (3.5%) with an uneventful course might have been diagnosed with gestational trophoblastic tumor and received needless chemotherapy based on the normal regression curve established by the Japan Society of Obstetrics and Gynecology or the US criteria of 4 consecutive plateauing or rising hCG values, respectively. CONCLUSIONS: Our more selective criteria for initiating chemotherapy in patients after evacuation of mole, i.e. hCG of 10,000 mIU/ml at 5 weeks, 1,000 mIU/ml at 8 weeks and nondetectable levels at 24 weeks after evacuation of mole, may be safe and acceptable in the management of patients after evacuation of mole.

Pregnancy after limb-sparing hemipelvectomy for Ewing's sarcoma. A case report and review of the literature.

Ewing's sarcoma of the bone is a malignant bone tumor occurring mostly in adolescence and was considered to have poor prognosis. With recent advances in multi-agent combined chemotherapy, prognosis has improved, and more patients with primary lesions in the pelvis opt for limb-saving surgeries. In the present case, Ewing's sarcoma in the left pelvis was diagnosed at the age of 11 and the patient underwent multi-agent chemotherapy combined with limb-sparing hemipelvectomy. She became pregnant at the age of 22. After an uneventful pregnancy, she delivered a healthy child at 37 weeks of gestation by cesarean section because of pelvic distortion. This is the first reported case of pregnancy and delivery after limb-sparing hemipelvectomy due to Ewing's sarcoma. Since the multi-modality treatment improves survival, the number of women with Ewing's sarcoma who desire pregnancy is expected to increase in the future. This is a valuable case that will provide useful information for such patients.

Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor.

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.

Changes in the incidence of molar pregnancies. A population-based study in Chiba Prefecture and Japan between 1974 and 2000.

BACKGROUND: The aim of this population-based retrospective study was to evaluate the trend in the incidence of molar pregnancy. METHODS: Questionnaires about the occurrence of hydatidiform mole were mailed to all clinics and hospitals in Chiba Prefecture between 1974 and 2000. The diagnosis of hydatidiform mole was based on the post-operative morphological and/or pathological findings. Data of live births were collected from the annual reports of maternal and child health statistics. A total of 3778 women with hydatidiform mole and 1 661 579 women with live births were analysed. RESULTS: The incidence of hydatidiform mole per 1000 live births was constant from 1974 to 1990, while it decreased significantly after 1991 (chi(2)-test for trend, P < 0.0001). The incidence of complete mole also decreased after 1991 (chi(2)-test for trend, P = 0.0001), though the incidence of partial mole remained unchanged. CONCLUSIONS: The incidence of hydatidiform mole in Chiba Prefecture has become as low as that in Europe or the USA, and it is attributed to the decreasing incidence of complete mole. A number of environmental factors that prevent the ovulation of 'empty' oocytes might have contributed to the decreasing incidence of complete mole.

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

BACKGROUND: 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). METHODS: From 1985 to 1997, 10 patients with refractory, high-risk GTTs were treated with the FA regimen at Chiba University Hospital. Of those 10 patients, 7 patients developed drug resistance to methotrexate, etoposide, and actinomycin D combination chemotherapy (the MEA regimen); 1 patient developed recurrent disease after receiving the MEA regimen; and 2 patients developed recurrent disease after receiving combination chemotherapy with etoposide, methotrexate, and actinomycin D alternating with cyclophosphamide and vincristine (the EMA/CO regimen). The hematologic toxicity of the FA regimen was graded at every chemotherapy course. RESULTS: With the FA regimen, the survival rate was 80.0% (8 of 10 patients) for a mean follow-up of 10 years. Two patients died due to multidrug resistance, and two patients subsequently developed recurrent disease. The two patients with recurrent disease were successfully salvaged again with the MEA regimen. The toxicity of the FA regimen was evaluated in 78 cycles. Myelosuppression seemed to be the dose-limiting toxicity, and the incidences of World Health Organization Grade 4 leukocytopenia and thrombocytopenia were 6.4% and 3.8%, respectively, of 78 cycles. CONCLUSIONS: Although etoposide-containing chemotherapy is currently the most effective and well-tolerated regimen for patients with high-risk GTTs, 20-30% of patients develop resistance to etoposide-containing regimens. Salvage combination chemotherapy with FA is effective for these patients with refractory disease, and the toxicity is predictable and manageable.

Detection of beta-subunit human chorionic gonadotropin mRNA in the peripheral blood of patients with nonmetastatic gestational trophoblastic disease.

OBJECTIVE: The aim of this study was to detect beta-subunit human chorionic gonadotropin (beta(h)CG) mRNA in the peripheral blood samples of patients with nonmetastatic gestational trophoblastic disease (GTD) undergoing hysterectomy. METHODS: Heparinized peripheral blood samples were obtained from four patients with nonmetastatic GTD before, during, and after hysterectomy. The beta(h)CG mRNA expression was examined by reverse transcriptase-polymerase chain reaction using beta(h)CG primers. The expression of beta(h)CG mRNA was quantified using a densitometer. RESULTS: Beta(h)CG expression was detected in all patients before and during hysterectomy. The expression of beta(h)CG mRNA during operation was so high that it could not be quantified using densitometer. The expression decreased rapidly after operation. CONCLUSIONS: Disseminated trophoblastic cells are present in the peripheral blood even in cases without metastasis. Trophoblastic cells circulating in the peripheral blood can be reduced by surgical intervention.

Outcome of subsequent pregnancy after treatment for persistent gestational trophoblastic tumour.

BACKGROUND: This study analysed subsequent pregnancy outcome in patients treated for persistent gestational trophoblastic tumour (GTT). METHODS: Between 1974 and 1999, a total of 378 patients with GTT (83 patients with high-risk and 295 patients with low-risk GTT) were treated at Chiba University Hospital, Japan. Of these 378 patients, 363 (96.0%) achieved primary remission and 315 survivors have been followed at our hospital. RESULTS: To date, 129 patients have had 243 subsequent conceptions. While pregnancy outcome was comparable with that of the general Japanese population, the incidence of repeat molar pregnancy (2.1%) was approximately seven times higher than that of the general population. During the mandatory HCG follow-up period of 1 year, 15 patients conceived within 6 months of completion of chemotherapy. The incidence of spontaneous abortion in these 15 patients was significantly higher than that in patients who conceived after a waiting period of >6 months (P = 0.0053). CONCLUSIONS: Patients treated for GTT may anticipate a normal future reproductive outcome, although it would be better to avoid pregnancy for at least 6 months after completion of chemotherapy.