Naohiko Umesaki

Evidence-based guidelines for treatment of cervical cancer in Japan: Japan Society of Gynecologic Oncology (JSGO) 2007 edition

Clinical practice guidelines for gynecologic cancers have been published by the National Comprehensive Cancer Network and the National Cancer Institute. Whereas these guidelines form the basis for the standard of care for gynecologic malignancies in the United States, it has proven difficult to institute them in Japan due to differences in patient characteristics, health-care delivery systems, and insurance programs. Therefore, evidence-based guidelines for treating cervical cancer specifically in Japan have been under development. The Guidelines Formulation Committee and Evaluation Committee were independently established within the Committee for Treatment Guidelines for Cervical Cancer. Opinions from within and outside the Japan Society of Gynecologic Oncology (JSGO) were incorporated into the final draft, and the guidelines were published after approval by the JSGO. These guidelines are composed of ten chapters and comprise three algorithms. Each chapter consists of a clinical question, recommendations, background, objectives, explanations, and references. The objective of these guidelines is to clearly delineate the standard of care for cervical cancer treatment in Japan in order to ensure equitable care for all Japanese women diagnosed with cervical cancer.

Postmenopausal intravenous leiomyomatosis with high levels of estradiol and estrogen receptor.

BACKGROUND Intravenous leiomyomatosis is a rare variant of leiomyoma. CASE The patient was a 49-year-old gravida 3, para 3 woman with menopause at age 46. She presented with a history of syncope. Vaginal examination revealed an enlarged and elastic-soft mass of the uterus. A pelvic ultrasound, computed tomography scan, and magnetic resonance imaging showed a heterogeneous, irregularly shaped 8- to 10-cm tumor. In addition, the inferior vena cava was almost completely occluded. Cardiac ultrasound demonstrated a mobile mass in the right atrium. The serum estradiol was 208 pg/mL (normal 0–59). Intravenous leiomyomatosis with cardiac extension was diagnosed preoperatively. A resection of the intracardiac and intracaval mass and a subtotal hysterectomy with bilateral salpingo-oophorectomy were performed. The uterine tumor weighed 600 g, and the cordlike intravascular tumor extending from the internal iliac vein into the right ventricle was 40 cm long and weighed 60 g. Pathologic examination confirmed intravenous leiomyomatosis with no evidence of atypia. The level of estrogen receptor in the tissue was 140 fmol/mg protein. The postoperative course was uneventful, and she has been in good health for 17 months after the operation. CONCLUSION We report a case of intravenous leiomyomatosis extending into the right ventricle treated with a one-stage operation. It is possible that a high concentration of serum estradiol and high level of tissue estrogen receptor are related to the intravenous leiomyomatosis.

Positron emission tomography using 2-[18F] fluoro-2-deoxy-d-glucose in the diagnosis of uterine leiomyosarcoma: A case report

Abstract The preoperative diagnosis of uterine leiomyosarcoma (LMS) is very difficult. Magnetic resonance (MR) imaging is usually used for it; however, precise diagnosis by MR imaging is limited to typical LMS with coagulative tumor cell necrosis. We presented a case of LMS that was diagnosed preoperatively by positron emission tomography (PET) using 2-[ 18 F] fluoro-2-deoxy-d-glucose (FDG).

Irinotecan (CPT-11) and Cisplatin as First-Line Chemotherapy for Advanced Ovarian Cancer

Objective: To evaluate the efficacy and toxicity of a combination of irinotecan (CPT-11) and cisplatin as first-line chemotherapy in advanced ovarian cancer. Methods: Twenty-six patients with previously untreated advanced epithelial ovarian cancer were enrolled in this study. CPT-11 60 mg/m2 was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m2 on day 1. Cycles were repeated every 28 days for at least two cycles. The median patient age was 55 years (range, 37–75), and the median performance status was 1. Results: Objective responses were recorded in 19 of 25 eligible patients (76%; 95% confidence interval, 55–91%). Complete responses were obtained in 2 patients (8%), and partial response in 17 patients (68%). Stable disease was recorded in 2 patients (8%) and progressive disease in 2 (8%). The median time to response was 62 days (range, 28–234 days). The median survival time for all 25 patients was 30.9+ months (range, 4.1–60.0+ months). The major toxic effects were leukopenia, neutropenia, and diarrhea. Grade 3 or 4 leukopenia, neutropenia, and diarrhea occurred in 17 (68%), 20 (83.3%), and 5 patients (20%), respectively. Thrombocytopenia was less common. No treatment-related deaths occurred. Conclusion: The combination of CPT-11 and cisplatin showed significant activity in chemotherapy-naive patients with advanced ovarian cancer. Neutropenia was the dose-limiting adverse effect, whereas diarrhea was mainly mild to moderate.

Phase II study of irinotecan plus doxorubicin for early recurrent or platinum-refractory ovarian cancer: interim analysis

The aim of this study was to evaluate the efficacy and toxicity of irinotecan and doxorubicin in the treatment of patients with early recurrent or platinum-refractory ovarian cancer. Nineteen woman from five different institutions were treated. Two patients had platinum-refractory cancer, 11 had platinum-resistant disease, and 6 had platinum-sensitive tumors. An intravenous infusion of Irinotecan (50mg/m2) was given on days 1, 8, and 15, while doxorubicin (40mg/m2) was administered as an intravenous bolus on day 3. This treatment schedule was repeated every 4 weeks. Among the 13 patients defined as having platinum-refractory/platinum-resistant disease, 4 patients achieved a clinical response (30.8%, 95% CI: 9.1–61.4), while only one of 6 patients defined as having platinum-sensitive disease achieved a clinical response (16.7%, 95% CI: 0.4–64.1). Leukopenia and neutropenia were the major dose- limiting toxicities. Grade 3 or 4 leukopenia and neutropenia were noted in 24 (48%) and 33 (66%) of the courses, while febrile neutropenia occurred in 2 courses. Five patients (26%) had grade 2 or worse diarrhea during 7 courses. Our data demonstrated that this regimen might be comparable to standard approved agents in patients with early recurrent or platinum refractory ovarian cancer.

MR and Ultrasound Imaging of Floating Globules in Mature Ovarian Cystic Teratoma

A rarely reported case of cystic teratoma with floating globules or fat balls is presented. Comparative imaging investigations of the floating globules in an ovarian cystic teratoma were performed using magnetic resonance and two- and three-dimensional ultrasound. Ultrasound imaging easily detected the floating globules, especially the 3-dimensional features showed almost the same findings that were observed macroscopically after surgery. Magnetic resonance thus clearly revealed the character of floating globules.

Two cases of vasa previa diagnosed prenatally using three-dimensional ultrasonography.

We report two cases in which we describe the impact of sonography (US) in the management of vasa previa. In the first case, with two‐dimensional US, the diagnosis of vasa previa was made at 21 weeks gestation. In the second case, using three‐dimensional US, the diagnosis of vasa previa was made at 19 weeks gestation. An elective Cesarean section was carried out at 34 weeks in both cases. Diagnosis of vasa previa is critical when low‐lying placenta or velamentous insertion of the umbilical cord is detected during the pregnancy.

Significance of peritoneal macrophages on fertility in mice

OBJECTIVE To elucidate the role of peritoneal macrophages in infertility, we investigated how the presence of peritoneal macrophages would affect fecundity in mice. Moreover, we also studied the effects of interleukin-1 on embryonic development. STUDY DESIGN Mice were administered OK-432 intraperitoneally to induce macrophage infiltration of the peritoneal cavity; ovulation was then induced and animals were mated. On day 13 of gestation, fetuses were counted. After injection of OK-432 or interleukin-1, the mice were mated. Three days later, embryos were collected and the stage of embryo development was determined. RESULTS In mice given OK-432 (n = 33), four (12%) became pregnant and the mean litter number was 6.0 +/- 3.6, whereas in the control group 23 of 30 mice (77%; p < 0.01) became pregnant and the litter number was 14.1 +/- 5.3 (p < 0.01). OK-432 and interleukin-1 administered intraperitoneally significantly suppressed embryo development (p < 0.01). CONCLUSION Increased numbers of peritoneal macrophages negatively affect fecundity, probably by suppressing embryonic development.

Direct effects of CPT-11 and SN38 on ovarian granulosa cells.

This study aimed to clarify the mechanism by which apoptosis and Fas ligand (FasL) expression are induced in the ovarian granulosa cells of mice injected with irinotecan HCl (CPT-11). To this end, the direct effects of CPT-11 and its active metabolite, SN38, on granulosa cells were investigated. Normal ovarian tissue fragments obtained from 8-week-old female MCH mice were cultured in vitro with CPT-11 or SN38 and paraffin-embedded. After sectioning, the ovarian fragments were analyzed by TUNEL staining to detect apoptotic cells and by immunohistochemistry with an anti-FasL antibody to detect FasL expression. The results revealed no increase in TUNEL-positive granulosa cells in the ovarian tissue fragments cultured with CPT-11 or SN38. Furthermore, CPT-11 and SN38 did not induce FasL expression in the ovarian fragments. In conclusion, apoptosis and FasL expression induced in the ovarian granulosa cells of mice injected with CPT-11 is not caused by direct stimulation with CPT-11 or SN38. Therefore, systemic CPT-11 administration appears to induce apoptosis and FasL expression in granulosa cells via currently unknown endogenous FasL-inducing factors or by active metabolites of CPT-11 other than SN38.

P11.17: Two cases of Pena-Shokier syndrome

The Silver-Russell syndrome (SRS) is characterized by severe intrauterine growth restriction, with a preserved head circumference, leading to a lean body habitus and short stature. Facial dysmorphism and asymmetry are considered typical features of the syndrome, although the range of phenotypic variance is unknown. A woman was transferred to our hospital due to decreased maternal serum α-fetoprotein (0.185 MoM), human chorionic gonadotrophin (0.128 MoM) and unconjugated estriol (0.775 MoM) at 16 weeks of gestation. Initial ultrasonographic findings showed oligohydramnios. But serial antenatal sonographic findings showed severe asymmetric intrauterine growth restriction (preserved head circumference, small abdominal circumference, and short femur) and both hydronephrosis with progressive oligohydramnios. Cytogenetic studies with GTG-banding by amniocentesis showed 46 XX, inv (9) (p11q13) and fetal karyotype was in paternal origin. On past history, the previous sibling of the fetus also showed severe asymmetric intrauterine growth restriction (31 weeks sized biparietal diameter, 25 weeks sized abdominal circumference, and 28 weeks sized femur length) with oligohydramnios at prenatal ultrasonography. After birth, she was diagnosed as SRS due to large cranium, broad forehead, microretrognathia, clinodactyly, and short philtrum with low birth weight and postnatal growth below to 2 SD from the mean. She died at 10 months of her age. At 26 weeks of gestation, fetal death in uterus was diagnosed and the fetus was delivered by labor induction. Autopsy findings showed asymmetric low birth weight (less than 5th percentile) with characteristic small triangular face, low set ears, clinodactyly and downward slanting corners of mouth. On the basis of these evidences, we diagnosed that this case was also SRS. We report a case of familial Silver-Russell syndrome with literatures.