Search

Angiogenesis is essential for the pathogenesis of endometriosis. Gene expression levels of vascular endothelial growth factor (VEGF) A and C in 10 eutopic endometrial, 23 normal peritoneal, and 62 endometriotic tissues surgically obtained from 47 women with endometriosis (group 2) were compared with those in 12 control eutopic endometrial and 9 normal peritoneal tissues from 15 women without endometriosis (group 1). VEGF-A mRNA expression levels in eutopic endometrium of group 2 were higher than those of group 1 throughout the menstrual cycle (P0.01) and increased in the secretory phase. VEGF-A gene expression in peritoneal endometriotic lesion was statistically higher than that in normal peritoneum (P0.01) and similar to that in eutopic endometrium of group 2. In contrast, gene expression levels of VEGF-C were relatively lower than those of VEGF-A in each lesion, and no cyclic variation was found. VEGF-A and C mRNA expression levels were significantly higher in ovarian endometriomas6 cm in size than in those6 cm in size. Immunohistochemical expression of VEGF-A and C was detected in the cytoplasm of glandular epithelial and stromal cells of ovarian endometrioma. These results suggest that endometriosis may arise from eutopic endometrium with higher levels of angiogenic activity possibly induced by VEGF-A in women with endometriosis. Moreover, VEGF-C as well as VEGF-A may be involved in the pathogenesis of ovarian endometrioma.

Objective Our purpose was to evaluate the safety, efficacy and procedural difficulties of intraoperative autologous blood transfusion during laparoscopic surgery for ectopic pregnancy. Design A retrospective study was performed. Methods The Cell Saver, an intraoperative autologous blood salvage device, was used in laparoscopic operations on 13 patients with ectopic pregnancy, who had haemoperitoneum but good physical status without severe anaemia and hypovolaemic shock. Results Homologous blood transfusion was not needed in any patient. The mean blood loss was 327±178 ml and the mean volume of reinfused processed blood was 288±92 ml. The haemoglobin level of reinfused processed blood was proportional to the blood loss. Neither adverse reactions to norprocedural difficulties of autotransfusion were observed. Conclusions When laparoscopic surgery is performed for ectopic pregnancy in patients with haemoperitoneum, intraoperative autologous transfusion employing the Cell Saver is considered to be a potentially very useful technique.

Objective: To evaluate how endometriosis affects expression of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in granulosa cells. Design: Prospective study. Setting: IVF-ET program at Osaka Medical College. Patient(s): Seventeen patients with revised American Fertility Society stage IV endometriosis and 17 patients with tubal infertility and no endometriosis. Intervention(s): Granulosa cells obtained at oocyte retrieval were examined for VEGF and IL-6 gene expression. Main Outcome Measure(s): Serum E 2 and P levels at hCG administration, number of oocytes, fertilization rate, high-quality embryo rate, and pregnancy rate, and expression of VEGF and IL-6 genes. Result(s): Total hMG and FSH levels were statistically significantly higher in patients with endometriosis; however, the number of retrieved oocytes and the fertilization rate were lower compared with patients with tubal infertility. Serum E 2 levels and expression of VEGF in patients with tubal infertility were statistically significantly higher than those in patients with endometriosis. Interleukin-6 gene expression did not differ between the groups. Conclusion(s): In severe endometriosis, lower VEGF gene expression in granulosa cells may adversely affect oocyte development and maturation.

Survivin is a novel inhibitor of apoptosis and is expressed during fetal development and in cancer tissues, but its expression has not been reported in normal adult tissues or benign diseases. We investigated survivin gene and protein expression in a tumor-like benign disease, endometriosis, and correlated them with apoptosis and invasive phenotype of endometriotic tissues. Gene expression levels of survivin, matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1 (MT1)-MMP in 63 pigmented or nonpigmented endometriotic tissues surgically obtained from 35 women with endometriosis were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. Survivin, MMP-2, MMP-9, and MT1-MMP mRNA expression levels in clinically aggressive pigmented lesions were significantly higher than those in normal eutopic endometrium, and survivin gene expression in pigmented lesions was also higher than that in nonpigmented lesions (P < 0.05). There was a close correlation between survivin and MMP-2, MMP-9, or MT1-MMP gene expression levels in 63 endometriotic tissues examined (P < 0.01). Apoptotic cells detected by the dUTP nick-end labeling were rare in 11 ovarian endometriotic tissues, which showed positive immunohistochemical expression for survivin and MMPs. Our findings suggest that up-regulation of survivin and MMPs may cooperatively contribute to survival and invasion of endometriosis.

The differential diagnosis of thrombotic microangiopathy (TMA) has become clearer following the establishment of the relationships between (1) diarrhea-associated hemolytic uremic syndrome (HUS) and Shiga toxin-producing Escherichia coli-HUS (STEC-HUS), (2) a markedly reduced ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) level and typical thrombotic thrombocytopenic purpura (TTP), and (3) abnormalities in the complement regulatory system and atypical HUS (aHUS). These TMAs include typical TTP, other forms of TMA, STEC-HUS, and aHUS. The pathological mechanisms of TMA still overlap among several forms of TMA. With respect to the management of TMA, the use of plasma exchange (PE) for typical TTP, additional steroid therapy for TMA and rituximab for typical TTP with a high titer of the inhibitor of ADAMTS-13, as well as eculizumab for aHUS, have also been established. Although several issues remain in the pathophysiology and management of TMA, new findings will hopefully resolve these problems in the near future.

Hemostatic markers are measured when diagnosing cases presenting with either thrombosis or thrombophilia. Decreased antithrombin (AT), protein C and protein S levels, and positive anti-phospholipid antibody findings together suggest a risk for venous thromboembolism (VTE). Increased thrombin AT complex (TAT) and soluble fibrin (SF) levels indicate a hypercoagulable state, and the addition of elevated fibrinogen and fibrin degradation products (FDP) as well as D-dimer suggests the presence of VTE. D-dimer is frequently measured in VTE cases, but this marker is affected by fibrinolysis and requires standardization. The prothrombin time, FDP and fibrinogen are all used in the diagnosis of disseminated intravascular coagulation. Markedly reduced ADAMTS13 level is a useful sign for the diagnosis of thrombotic thrombocytopenic purpura.

Abnormalities of the hemostatic system in patients with DIC result from the sum of vectors for hypercoagulation and hyperfibrinolysis. DIC is classified into hyperfibrinolysis, hypercoagulation, massive bleeding or nonsymptomatic types according to the balance of the two vectors. Both the antithrombin (AT) and protein C (PC) levels are significantly low in patients with septic DIC, and reduced amounts of AT and PC result in the lack of inhibition of thrombin and activated FVIII, respectively. Thrombin activates FVIII, while activated FVIII accelerates the coagulation pathway to generate thrombin; thus activation of the coagulation system persists. Three sets of diagnostic criteria have been established by the Japanese Ministry of Health, Labour and Welfare, International Society of Thrombosis and Haemostasis and Japanese Association for Acute Medicine, respectively. Although these three diagnostic criteria score hemostatic abnormalities using similar global coagulation tests, the sensitivity and/or specificity for death differ. Treatment with AT or activated PC may not improve the outcomes of patients with sepsis at the early stage, although they may improve the outcomes in those with DIC. Therefore, new diagnostic criteria for determining the appropriate time to initiate anticoagulant treatment are required.

Background It is now possible for leukocyte-depletion filters to be used for removing malignant cells from blood during autotransfusion in patients with malignant tumors. With the objective of ascertaining its clinical application in gynecologic surgery for malignant tumors, we have performed a basic investigation of the malignant cell depletion performance of the BPF4-BJ, a new, fourth-generation leukocyte-depletion filter.

A 52-year-old woman had a primary neuroendocrine tumor, Grade 2(NET G2)with multiple liver metastases and a mesenteric tumor. Since no drugs were approved for NET at that time in Japan, we treated her with sunitinib after approval by the Ethics Committee of Mie University Hospital and obtaining informed consent. Sunitinib was administered at a daily dose of 37.5mg/day, but the dose was reduced to 12.5mg/day because of thrombocytopenia(G3)and neutropenia(G3). CT revealed stable disease after 3 months of treatment, but disease progression was observed after 11 months. The non-hematological toxicity was hypertension(G3), which was controlled with antihypertensive agents. Although there are no previous reports of the treatment of well-differentiated NET with sunitinib in Japan, sunitinib may be effective against this disease.

Examination of the mitochondrial mRNA expression in granulosa cells from an unspecified population of infertile patients to evaluate whether recombinant follicle stimulating hormone (recFSH) is more effective in producing higher quality embryo rates compared with human menopausal gonadotropin (hMG).Thirty-nine patients who underwent the in vitro fertilization and embryo transfer program were retrospectively examined. Patients were administered recFSH (The high-quality embryo rate in the hMG cycle was higher than in the recFSH cycle, and the total dose of hMG showed a positive correlation with the expression level of mitochondrial genes in granulosa cells. Moreover, mitochondria mRNA expression was higher in the hMG cycle than in the recFSH cycle.Compared with recFSH, hMG induces a higher mitochondrial gene expression ratio in granulosa cells at the time of oocyte retrieval and, therefore, may lead to higher quality embryo rates.

The experimental angular distributions for the reaction 7Li(p, α)4He at incident energies of 271, 416 and 561 keV below the Coulomb barrier are analyzed with the finite-range distorted-wave-Born-approximation formalism including both the direct and the exchange processes. The spectroscopic amplitudes used in the present analysis are obtained so as to fit the experimental angular distributions for the same reaction at the proton bombarding energy of 45.2 MeV. Good agreements between theoretical calculations and experiments are obtained in regard to both the shape and the absolute magnitude of the differential cross section. Numerical calculations show that the direct-reaction mechanism is dominant for the reaction 7Li(p, α)4He; in particular, the exchange process plays an important role for reproducing the experimental angular distributions in keV energy ranges.

Objectives G protein-coupled receptor 30 (GPR30) is a 7-transmembrane estrogen receptor that functions alongside traditional estrogen receptors to regulate the cellular responses to estrogen. Recent studies suggest that GPR30 expression is associated with a poor prognosis, and that this is due to the GPR30-mediated transactivation of the EGFR in breast cancer. However, the biological contribution of GPR30 in ovarian cancer remains unclear. The purpose of this study was to elucidate the relationships between GPR30 expression and the clinicopathological findings, and to determine how the signaling cascade influences the prognosis of ovarian cancer. Methods The expression levels of GPR30, EGFR, ERα, and ERβ were analyzed using an immunohistochemical analysis, and their correlations with the clinicopathological features were examined in 10 patients with borderline malignant tumors and 152 patients with epithelial ovarian cancer. We also examined whether GPR30 signaling activates the EGFR-Akt pathway in an ovarian cancer cell line (Caov-3) by a Western blotting analysis. Results The GPR30 expression in ovarian carcinomas was significantly higher than that in borderline malignancies (p=0.0016), and was not associated with the expression of the EGFR, ERα, or ERβ. The expression of GPR30 in clear cell carcinomas was significantly lower than that in other subtypes of cancer (P Conclusion The expression of both GPR30 and EGFR is associated with a poor outcome in ovarian cancer, and GPR30 increases the phosphorylation of Akt via the EGFR in ovarian cancer cells. The regulation of GPR30 might be a potentially useful new therapeutic target in ovarian cancer.

For the energy-resolved computed tomography (CT), the authors developed a current mode X-ray detector, a "transXend detector", which measures X-rays as electric current and gives X-ray energy distribution after analysis. As an application of the transXend detector, thickness distributions of materials are estimated with one transmission measurement, with using two-dimensional map made of the ratio of measured electric currents. With two transmission measurements, a tomography is reconstructed. Large reduction of dose exposure in CT is expected with this method.

To examine the associations between the pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes in Japanese women.The medical records of 1883 Japanese women who delivered singleton infants from January 2010 to January 2013 at Osaka-Minami Medical Center were retrospectively reviewed. We use the BMI classification which the World Health Organization defined for Asian populations and the GWG classified based on the current 2009 Institute of Medicine (IOM) recommendations. The odds ratio (OR) of each of the groups for the different pregnancy outcomes were compared to the recommended group using a logistic regression analysis adjusted by age, gestational weeks, parity, weight gain, mode of delivery, pregnancy induced hypertension (PIH) and gestational diabetes mellitus.Women who were obese (BMI, ≥25 kg/m(2) ) and overweight (BMI, 23-24.9 kg/m(2) ) had a higher rate of developing PIH (adjusted OR, 6.68 and 3.21 [95% confidence interval [CI], 3.31-13.3 and 1.29-7.24]). In contrast, GWG exhibited a correlation with the weight of the infant. The inadequate GWG group had a higher rate of small-for-gestational age (SGA) infants (adjusted OR, 1.72 [95% CI, 1.22-2.46]). The rate of emergency cesarean section was not significantly different between the groups.A pre-pregnancy BMI less than 23 kg/m(2) is desirable to prevent Japanese women from developing PIH. GWG within the IOM recommendations also reduced the risk of PIH and SGA.

The purpose of this study was to compare the intraoperative and postoperative parameters among the three approaches used to treat large uterine myomas: laparoscopic assisted vaginal hysterectomy (LAVH), total laparoscopic hysterectomy (TLH) and abdominal hysterectomy, and to evaluate the selection criteria for laparoscopic hysterectomy as determined by magnetic resonance imaging.The medical records of 155 patients who underwent a hysterectomy between January 2007 and April 2010 were examined. We also compared the indications and outcomes of LAVH and TLH for myomas larger than 7 cm.Patients who underwent LAVH or TLH had a lower average intraoperative blood loss, less intense postoperative pain, and shorter hospital stays than patients in the TAH group, although the length of the operations in the laparoscopic groups were significantly longer. To evaluate the selection criteria for the large sized myomas, we compared the LAVH and TLH groups for the myomas larger than 7 cm. The greatest uterine transverse diameters and the weight of the uteri were not significantly different between the LAVH and TLH groups (94.7 ± 20.8 and 83.1 ± 17.6 mm, 371.6 ± 160.3 and 286.7 ± 158.0 g, respectively). The average intraoperative blood loss in the TLH group was significantly lower than that in the LAVH (121.3 ± 111.2 vs 379.3 ± 222.4 g, P0.001).Our data suggest that TLH is a better procedure for treating a large uterus no larger than 10 cm in its greatest transverse diameter. The preoperative total length of myoma nodules determined by MRI is a useful preoperative indicator of the uterine weight.

BackgroundEndometriosis is one of the most common gynecological diseases associated with infertility. Endometriosis may affect the androgen receptor (AR) mRNA expression in human granulosa cells and the methylation of the promoter region of AR. We investigated 28 patients with endometriosis and 47 subjects without endometriosis undertaking IVF treatment.MethodsGranulosa cells were obtained from 28 patients with endometriosis and 47 subjects without endometriosis as a control. Expressions of AR and FSHR mRNA were then evaluated by OneStep real-time PCR analysis, and the level of methylation of the promoter region was qualified by methylation-specified PCR (MSP).ResultsThe expression of AR mRNA in the endometriosis group was statistically lower than that in the control group. As well, FSHR mRNA expression in the control group showed a positive correlation with AR mRNA expression; however, there was no such correlation in endometriosis patients. In the control group, AR mRNA expression was statistically higher in pregnant subjects compared with non-pregnant subjects; however, in the endometriosis group, no significant difference was identified. The promoter of AR was heavily methylated in all endometriosis cases; however, only 5 (45.4%) were methylated in the control group.ConclusionLower AR mRNA expression and methylation of the AR promoter region might affect the expression of AR and FSHR the presence of endometriosis, thus leading to a disturbance in the regulation of AR and FSHR.

We performed a prenatal diagnosis for 10 fetuses from nine unrelated Japanese xeroderma pigmentosum complementation group A (XP-A) families. All parents had at least one XP-A child (proband) with a homozygous founder mutation (IVS3-1GC) in the XPA gene. A genetic analysis was performed by a restriction enzyme; AlwNI fragment length polymorphism of polymerase chain reaction (PCR)-amplified DNA, mostly from amniotic fluid (AF) and cultured cells established from AF. However, for the first family, we tried amniocentesis as well as chorionic villus sampling (CVS). Among the 10 cases, we confirmed the results of PCR-based genetic diagnosis by post-ultraviolet survival of amniotic cells in eight cases. Unfortunately, 6 weeks after CVS and 4 days after the amniocentesis in the first case we examined, the fetus died in utero, the reason for which remains unexplained. We prenatally determined two XP-A cases, six XP-A carriers and two wild-type fetuses, which appears to be consistent with Mendel's law.

A 60-year-old female was diagnosed as advanced gastric cancer with multiple bone, neck and mediastinal lymph node metastases. As a primary chemotherapy, she was treated with S-1(50 m g/body, twice daily for 4 weeks, followed by a 2- week rest). After 3 courses of S-1, she developed a disease progression with pulmonary lymphangitic carcinomatosis and disseminated intravascular coagulation(DIC). Therefore, she received second-line chemotherapy of irinotecan(CPT-11 150 mg/m2, biweekly). Within 3 weeks of starting the treatment, the clinical and laboratory signs of DIC were dramatically resolved. There have been no previous reports of irinotecan alone showing such remarkable effectiveness in a patient with 5- FU-resistant gastric cancer with DIC.

We herein assessed the influence of Epidermal Growth Factor Receptor (EGFR) gene mutations on EGFR expression levels, downstream mediators such as Akt or ERK, and overall survival in patients with ovarian cancer.EGFR mutation status was analyzed by direct sequencing in 102 Japanese ovarian cancer patients. The EGFR expression, phosphorylated Akt (pAkt), and phosphorylated ERK (pERK) were determined by immunohistochemistry.Twenty-nine EGFR gene mutations were detected in 24 of 102 patinets (23.5%). EGFR mutations were observed in 27.9% (19/68) in serous adenocarcinomas, 15.0% (3/20) in clear cell adenocarcinomas, and 66.7% (2/3) in mucinous adenocarcinomas, while no mutations were observed in endometrioid adenocarcinomas (0/11). Protein expression of EGFR, pAkt, and pERK were detected in 47 (46.1%), 49 (48%), and 17 (16.7%) of patients, respectively. EGFR gene mutations, EGFR and pERK expression were not associated with a poor prognosis. In a multivariate analysis, a High pAkt expression was found to be a significant predictor for both the progression free survival (p=0.017) and overall survival (P=0.025).EGFR gene mutations were frequently observed in not only non-small-cell lung cancer (NSCLC), but also in ovarian cancer in Japanese patients. the selective EGFR inhibitor Gefitinib might therefore offer some benefit in patients with EGFR mutations in ovarian cancer. Our results indicate that the Akt, but not necessarily EGFR, is one of the most important target in the response of the platinum-based chemotherapy and prognosis for ovarian cancer patients.

19 F(p, a)'"O(g.s.) at incident energies of 250, 350 and 450 keV below the Coulomb barrier are analyzed with the finite-range distorted wave Born approximation formalism including both the direct and exchange processes. In order to treat in a consiste~t way the reaction mechanism of the reaction of the ' 9 F(p, a) 16 0(g.s.) at keV and MeV energy ranges, we adopt the value of the spectroscopic amplitude obtained by the analysis of the experimental angular distribution for the same reaction at Ep=18 MeV. Good agreements between theoretical calculations and experiments are obtained. Especially, the energy dependence of the differential cross section is nicely fitted to the data. Numerical calculations show that the direct reaction mechanism is dominant for this reaction, in particular the exchange process plays an important role for reproducing the experimental angular distributions in keV energy ranges.

Although patients with gynecological malignancies now survive longer due to advances in early diagnosis and therapy, major issues still remain regarding the quality of life for the survivors. Surgical menopause increases the risk of atherosclerosis; however, few studies have investigated the influence of platinum-based adjuvant chemotherapy. This study was conducted to evaluate the effects of platinum-based chemotherapy on atherosclerosis.This study enrolled 47 women (26 with ovarian cancers and 21 with endometrial cancers) who underwent surgical treatment, with or without platinum-based adjuvant chemotherapy, according to established protocols between 2007 and 2009. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) performed before surgery, and subsequently at 12 months after treatment. The flow-mediated dilatation of the brachial artery was measured before and immediately following chemotherapy to evaluate the vascular endothelial damage. Human umbilical vein endothelial cells (HUVECs) were used to evaluate cisplatin-induced vascular endothelial dysfunction in vitro.Although there were no significant differences in the baPWV associated with surgical treatment, platinum-based chemotherapy was associated with an increased baPWV. Significant decreases of flow-mediated dilatation were observed immediately following chemotherapy. An in vitro examination demonstrated that cisplatin attenuated nitric oxide production via inhibition of Akt-eNOS cascades in HUVECs.This research suggests that platinum-based chemotherapy directly induces vascular endothelial dysfunction and may be a risk factor for the development of atherosclerosis. Therefore, gynecologic cancer survivors should be educated about these potential risks, and informed regarding lifestyle modifications that may benefit their general health.

Topotecan, a novel topoisomerase-1 inhibitor, is a drug that appears to be effective against platinum-resistant ovarian cancers. However, the molecular mechanisms by which Topotecan treatment inhibits cancer cell proliferation are unclear. We investigated whether Topotecan increases the efficacy of Cisplatin in platinum-resistant ovarian cancer models in vitro and in vivo.We used Cisplatin-resistant Caov-3 cells and Cisplatin-sensitive A2780 cells. We examined the effect of Cisplatin and Topotecan on the cell viability of Caov-3 and A2780 cells by MTS assay. We examined the Akt kinase activity, VEGF and HIF-1α expression after Cisplatin and Topotecan by a Western blot analysis. Moreover, we also evaluated the effects of Cisplatin and Topotecan on the intraabdominal dissemination of ovarian cancer in vivo.Topotecan significantly inhibited Cisplatin-induced Akt activation in Caov-3 cells, but not in A2780 cells. In the presence of Topotecan, Cisplatin-induced growth inhibition and apoptosis were significantly enhanced in Caov-3 cells. Topotecan inhibited not only Cisplatin-induced Akt activation but also VEGF and HIF-1α expression. Moreover, treatment with Topotecan increased the efficacy of Cisplatin-induced growth inhibition in the intraabdominal dissemination and production of ascites in athymic nude mice inoculated with Caov-3 cells.We herein demonstrated that Topotecan inhibits Akt kinase activity and VEGF transcriptional activation after Cisplatin treatment in platinum-resistant ovarian cancers. We clarified how Topotecan enhanced the clinical activity in the platinum-resistant ovarian cancer. These results provide a rationale for using Topotecan in clinical regimens aimed at molecular targeting agents in platinum-resistant ovarian cancers.

During human pregnancy, trophoblasts play an important role in embryo implantation and placental development. Cytotrophoblast cells invade the uterine spiral arteries and differentiate into extravillous trophoblasts, resulting in the remodeling of the uterine vessels and fetoplacental vasculature. During early pregnancy, a physiologically hypoxic environment induces the production of angiogenic factors, such as vascular endothelial growth factor (VEGF), which are suggested to locally control the vascular remodeling. Endoglin, a cell-surface coreceptor for transforming growth factor-β1, is highly expressed in endothelial cells and syncytiotrophoblasts, and can be associated with endothelial nitric oxide synthase and vascular homeostasis. Several studies have recently suggested that some pregnancy-related complications, such as preeclampsia, have their origins early in pregnancy as a result of abnormalities in implantation and placental development. Although angiogenic factors are recognized as key molecules in placental development, little is known about the mechanism(s) of their regulation in trophoblasts. In this study, we elucidated the mechanisms underlying the regulation of VEGF and endoglin production under hypoxic conditions in the trophoblast-derived cell line, BeWo. We evaluated the role of the AKT–MTOR cascade and ERK kinase in the expression of VEGF and endoglin in response to hypoxia using various kinase inhibitors and small interfering RNA targeted against hypoxia-inducible factor (HIF)-1α (listed as HIF1A in Hugo Database). Our results suggest that both the phosphatidylinositol 3-kinase–AKT–MTOR–HIF-1α and ERK–HIF-1α signaling pathways are crucial for increasing VEGF and endoglin expression in response to hypoxia in BeWo cells.

Objective To report a case of mature cystic teratoma of the fallopian tube. Design Case report. Setting Medical college–affiliated hospital. Patient(s) A 31-year-old woman, gravida 0, visited our outpatient clinic with infertility. Hysterosalpingography (HSG) showed a swollen right fallopian tube whose patency was not confirmed. Intervention(s) Laparoscopic right salpingectomy was perfomed for a solid-appearing mass ∼2 × 1.5 cm in diameter in the ampullary region. Histopathologic examination showed components from each germ cell layer; therefore, the diagnosis of a mature cystic teratoma of the right fallopian tube was confirmed. The patient became pregnant with IVF-ET and gave birth to a baby boy. Conclusion(s) In cases where hydrosalpinx is suspected, a careful assessment by either HSG or laparoscopy is necessary at the time of infertility examination.

Objective To report a case of successful pregnancy after conservative surgery for stage 1A endometrial cancer. Design Case report. Setting University hospital. Patient(s) A 33-year-old woman who was diagnosed with stage IA endometrial cancer. Intervention(s) Conservative surgery and chemotherapy. Main Outcome Measure(s) Clinical outcome. Result(s) After administering medroxyprogesterone acetate (MPA) for 6 weeks, hysterofiberscopy showed that the restricted lesions still remained. A partial resection of the lesions was therefore performed. The patient delivered a girl by cesarean section after the surgery. Conclusion(s) Conservative surgery after MPA treatment may be a new treatment option for patients who wish to preserve their fertility.

We report the therapeutic potential, longterm survival, and toxicity of neoadjuvant intraarterial chemotherapy (NAIC) using an original four-lumen double-balloon (4L-DB) catheter followed by radical hysterectomy and/or radiotherapy in patients with locally advanced cervical cancer. Sixty patients with stage IIB-IVA cervical squamous cell cancer were treated with NAIC which included cisplatin (60–70 mg/m2, day 1), mitomycin-C (10–20 mg/m2, day 1), and pirarubicin hydrochloride (THP; 10–20 mg/m2, day 1) for two courses every 21 days. The median follow up among surviving patients was 93.7 months. Among 60 eligible patients, 22 had a complete response (CR; 36.7%) including 12 with a pathologic CR (20.0%). Thirty-six patients had a partial response (60.0%), and stable disease was observed in only 2 patients (3.3%). Moreover, we found that the platinum concentration in the cervix was correlated with the clinical response (P < 0.001). The 10-year progression-free survival (PFS) and 10-year survival were 90.9% and 90.9%, respectively, in patients with stage IIB disease and 66.0% and 70.7%, respectively, in patients with stage III disease. Leukopenia occurred in 86.7% of patients, but it was not very severe (grade 3, 4 in 13.3% of patients). Our results with NAIC using the 4L-DB catheter in locally advanced cervical cancer demonstrate that a high platinum concentration has beneficial effects on primary lesions and improves long-term progression-free and overall survival.

The aim of the present investigation was to evaluate the clinical efficacy of Xiong-gui-tiao-xue-yin, a traditional Japanese herbal medicine, in stimulating lactation in the postpartum period. We enrolled 82 women who had a normal delivery in Osaka Medical College Hospital, and randomly assigned them to the following two groups: a group of 41 women who received Xiong-gui-tiao-xue-yin at a dose of 6.0 g/day (Group X), and a group of 41 women who received ergometrine (methylergometrine maleate) at a dose of 0.375 mg/day (Group E). Volume of lactation was determined daily until Day 6 postpartum. Plasma prolactin and oxytocin concentration were measured at Days 1 and 6 postpartum. The results showed that volume of lactation was significantly higher in Group X than in Group E at Days 4 ( p = 0.042), 5 ( p = 0.038), and 6 ( p = 0.046). Significant differences between Groups X and E were noted in plasma prolactin concentration at Days 1 (157.9 ± 78.2 ng/ml and 129.1 ± 64.8 ng/ml ; p = 0.037) and 6 (167.5 ± 95.4 ng/ml and 117.1 ± 53.6 ng/ml ; p = 0.0042) postpartum. On the other hand, at Day 1, oxytocin concentration was significantly higher in Group E than in Group X ( p = 0.0024). No adverse effects were observed in this study. The results of our study demonstrate the beneficial effects of Xiong-gui-tiao-xue-yin on lactation, with increase in prolactin level without increase in oxytocin level in the postpartum period. Therefore, Xiong-gui-tiao-xue-yin can be expected to improve lactation in women in the postpartum period. Further detailed bio-pharmacological studies and clinical trials to investigate the properties of this drug are warranted.

This study was carried out to evaluate the clinical efficacy of Xiong-gui-jiao-ai-tang (Kyuki-kyogai-to), a traditional Chinese herbal medicine, in the treatment of threatened abortion in early pregnancy. We enrolled 72 women diagnosed with threatened abortion at Osaka Medical College Hospital and assigned them at random to the following two groups: a group of 36 women who received Xiong-gui-jiao-ai-tang at a dose of 7.5 g/day and another group of 36 women who received human chorionic gonadotropin (hCG)(control group). We found that in the Xiong-gui-jiao-ai-tang group (2.9 ± 3.5 days), the number of days required before hemostasis was reached in the uterus was significantly shorter than in the control group (10.8 ± 8.2 days, p < 0.0001). Furthermore, the number of days required for retroplacental hematoma in the vicinity of the gestational sac to disappear was significantly shorter in the Xiong-gui-jiao-ai-tang group (9.9 ± 7.1 days) than in the control group (23.2 ± 12.8 days) ( p < 0.0001). In retroplacental hematoma size, significant rates of reduction were obtained in both major and minor axis measurements at the 7th day of treatment for the Xiong-gui-jiao-ai-tang group compared to the control group (control vs Xiong-gui-jiao-ai-tang: major axis: 7.5 ± 3.8% vs 42.3 ± 10.5%; minor axis: 15.3 ± 16.8% vs 71.5 ± 48.2%)( p < 0.0001, each case). The results of this study demonstrated the beneficial effects of Xiong-gui-jiao-ai-tang in stabilizing early pregnancy. Xiong-gui-jiao-ai-tang can be expected to improve unstable early pregnancy with uterine bleeding and to prevent abortion.

Objective To evaluate survivin gene expression in granulosa cells from infertile patients and examine the relationship between survivin gene expression and infertile clinical background. Design Prospective study. Setting IVF-ET program at Osaka Medical College. Patient(s) Twenty-eight patients underwent ovulation induction for IVF-ET performed because of tubal infertility, male factor infertility, or endometriosis. Intervention(s) Granulosa cells obtained at oocyte retrieval were examined for survivin gene expression by quantitative reverse transcription-polymerase chain reaction. Main Outcome Measure(s) Hormone environment, number of oocytes, fertilization rate, high-quality embryo rate, pregnancy rate, and expression of survivin genes. Result(s) Survivin gene expression was detected in all granulosa cells. The gene expression levels of survivin in patients with endometriosis were significantly lower than those in patients with male factor infertility. The gene expression levels of survivin in total pregnant patients were higher than those in total nonpregnant patients and than those in the male factor infertility group, and there was no correlation between gene expression level and serum E 2 level. Conclusion(s) Survivin may be used as an indicator of the success of IVF-ET, and the existence of endometriosis may elevate the apoptosis of granulosa cells.

The expression of mitochondrial genes in granulosa cells was quantitated by real-time polymerase chain reaction. The expression ratio of mitochondrial genes in granulosa cells of patients with severe endometriosis showed no statistically significant difference compared with cases of tubal infertility without endometriosis.

Survivin is a novel inhibitor of apoptosis (IAP), and the two splice variants of survivin (survivin-2B and survivin-EX3) have been identified. Gene expression levels of survivin, survivin-2B and survivin-EX3 in 56 ectopic (16 peritoneal red and 16 peritoneal black lesions and 24 ovarian endometriomata) and 13 eutopic endometrial tissues surgically obtained from 42 women with endometriosis (group A) were compared with those in 16 control eutopic endometrium from 16 women without endometriosis (group B) by quantitative RT-PCR analysis. Survivin mRNA expression levels in ectopic endometriotic tissues were significantly higher than those in eutopic endometrium of groups A and B over the whole cycle. Red peritoneal lesions had higher gene expression levels of survivin than black lesions. In contrast, all tissue samples examined showed relatively lower gene expression levels of survivin-2B and survivin-EX3. No cyclic variation was found in survivin and the two splice variants, both in ectopic and in eutopic endometrium. Although there was no significant difference in the ratio of survivin-2B/survivin between ectopic and eutopic endometrium, the ratio of survivin-EX3/survivin in peritoneal endometriotic lesions was significantly higher than that of eutopic endometrium of groups A and B. These results suggest that survivin and survivin-EX3 may be closely linked to escape from apoptosis and the development of endometriosis.

Objective: To determine the influence of fertility treatments on multiple pregnancy rates. Study Design: A retrospective audit of women with multiple pregnancies from 1996 to 2001 at National Women's Hospital (NWH), Auckland, New Zealand was conducted. Information was collected regarding the demographics, fertility treatment, outcome of the pregnancy and complications experienced by women discharged with multiple births as an discharge diagnosis. Results: For the years 1996–2001 there were 1136 multiple births at NWH. Of these births, 201 (18%) were conceived following fertility treatment. Seventeen percent of twin births and 44% of triplet births were conceived following fertility treatment. There was a statistically significant increase in the number of births conceived following fertility treatment, from 9% in 1996 to 24% in 2001, although the proportion of births that were multiple overall did not change (2% in 1996 and 2.3% in 2001). Sixty-three percent of all fertility conceived multiple births were following in vitro fertilization/intracytoplasmic sperm injection treatment. Sixty percent of these women had two embryos transferred and 31% had three embryos transferred. Ovulation induction with follicle-stimulating hormone accounted for 19% of all fertility conceived multiple births. Nineteen percent of fertility conceived multiple births followed clomiphene treatment alone. Conclusions: The proportion of multiple pregnancies as a result of fertility treatments has increased over the 6 years studied.

To assess the clinical efficacy of Unkei-to in women with luteal phase defects.A study of 103 consecutive subjects with luteal phase defects treated with unkei-to (7.5 g/d) and 94 control subjects was conducted. A venous blood sample was taken, and plasma gonadotropins, 17 beta-estradiol and progesterone levels were measured. Dominant follicle size and endometrial thickness were assessed in the late follicular phase.Unkei-to significantly decreased plasma luteinizing hormone and significantly increased 17 beta-estradiol concentration in the follicular phase and significantly increased progesterone (66.7%) in the midluteal phase (P.05). Significant development of the dominant follicle (P.01) and endometrium (P.001) was also observed in patients treated with unkei-to. We observed significant prolongation of the luteal phase (43%, P.001) as measured by basal body temperature. There was a 79.6% rate of correction of luteal phase defects in patients treated with unkei-to. Furthermore, the pregnancy rate in patients desiring pregnancy was 49.5% (41/83).Administration of unkei-to may normalize the gonadotropin-ovarian endocrine system and/or their interaction in the follicular phase and may improve the endocrine environment in the luteal phase in patients with luteal phase defects.

Various types of cell adhesion molecules and matrix metalloproteinases (MMPs) seem to play an important role in the invasion process of endometriosis; however, limited investigation has focused on their gene expression in human peritoneal endometriotic lesions. A total of 63 endometriotic tissues were surgically obtained from 35 women with endometriosis, which included 43 pigmented and 20 non-pigmented lesions. Gene expression levels of E-cadherin, alpha- and beta-catenin, MMP-2, MMP-9 and membrane-type 1 (MT1)-MMP in these endometriotic lesions were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. MMP-2, MMP-9 and MT1-MMP mRNA expression in pigmented lesions was significantly higher than that in normal endometrium (p < 0.05), whereas E-cadherin, alpha- and beta-catenin mRNA expression was not suppressed in endometriotic lesions. There was a close correlation between MMP-2 or MT1-MMP and E-cadherin, alpha- or beta-catenin gene expression in 63 endometriotic tissues examined (p < 0.01). Immunohistochemical expression of E-cadherin, alpha- and beta-catenin in glandular epithelial cells was positive not only for all of seven cases with normal eutopic endometrium but also for 9 of 11 with ovarian endometriosis. MMP expression in ectopic endometrium was much greater than that in eutopic endometrium. These results suggest that endometriotic tissues expressing MMPs might be invasive and simultaneously possess cell-to-cell adhesion property in pelvic peritoneal foci.

A total of 63 pigmented or non-pigmented endometriotic, 26 endometrial carcinoma, and 12 normal eutopic endometrial tissues were examined for mRNA expression of survivin, matrix metalloproteinase (MMP)−2, MMP−9, and membranetype 1 (MT1)−MMP. The expression levels of the survivin and MMPs genes in clinically aggressive pigmented lesions were significantly higher than those in normal eutopic endometrium, and survivin gene expression in pigmented lesions was also higher than that in non-pigmented lesions (P < 0.05). There was a close correlation between the expression levels of the survivin and MMPs genes in 63 endometriotic tissues examined (P < 0.01). Apoptotic cells detected by dUTP nick-end labeling were rare in 11 ovarian endometriotic tissues, which showed positive immunohistochemical expression for survivin and MMPs. Expression levels of the survivin and MMPs genes in endometrial carcinomas were higher than those in normal eutopic endometrium and were well correlated with the depth of myometrial invasion (P < 0.05). There was a close correlation between the expression levels of the survivin and MMPs genes in 26 endometrial carcinoma tissues examined (P < 0.01). These findings suggest that upregulation of survivin and MMPs may contribute cooperatively to survival and invasion of endometriosis and endometrial carcinomas.

The correlation between vascular endothelial growth factor (VEGF)-C gene expression and in vitro invasive activity and matrix metalloproteinase (MMP)-2 or 9 gene expression and proteolytic activity in 11 cervical carcinoma cell lines, was investigated. Immunohistochemical expression of VEGF-C in 52 cervical carcinoma tissues was also correlated with tumor aggressiveness with respect to clinicopathologic features, tumor vascularity, MMP-2 expression and patient outcome. Expression of VEGF-C mRNA differed remarkably among the cell lines and there was a statistical correlation between VEGF-C gene expression and the number of invaded tumor cells (p = 0.0009) and MMP-2 gene expression and activity (p < 0.05). Anti-VEGF-C antibody inhibited the invasive and proteolytic activity of tumor cells in a concentration-dependent manner. VEGF-C or MMP-2 expression in clinical tissue samples was well correlated with depth of myometrial invasion, endometrial invasion, pelvic lymphnode metastasis and tumor vascularity (p < 0.05) and there was a close relation between VEGF-C and MMP-2 expression (p < 0.0001) in cervical carcinomas. Overall survival rates for 14 patients with strong VEGF-C staining tumors were lower than those for 38 patients with weak VEGF-C staining tumors (p = 0.0132) and VEGF-C tissue status emerged as an independent prognostic parameter (p = 0.0232). These results suggest that VEGF-C expression is closely related to invasion phenotype and affects the patient's survival in cervical carcinomas. © 2002 Wiley-Liss, Inc.

Introduction: The double therapy of trastuzumab and pertuzumab (TP) will come into widespread use, because of the beneficial effects on HER2 positive breast cancer. However, we don't have enough information about the safety of TP in Japanese patients. In our hospital, triple therapy of eribulin and TP for previously treated HER2 positive breast cancer is ongoing (UMIN000012018). In this study, we assessed the safety of TP, including the data of participants in the triple therapy trial. Patients and methods: We assessed the safety of 8 patients who were administered TP in our hospital. Adverse events (AEs) were graded according to CTCAE v4.0. Results: Five patients were administered TP with eribulin, three patients were administered TP without cytotoxic agents. The most common AEs were diarrhea (4 patients), leukopenia (3 patients), neutropenia (3 patients), hypokalemia (3 patients), infusion reaction (3 patients), lymphopenia (2 patients), stomatitis (2 patients), skin disorders (2 patients). Hematologic toxicity, diarrhea, hypokalemia, stomatitis were frequently observed in patients who were administered TP with eribulin. Grade 3 AEs were neutropenia (2 patients), leukopenia (1 patient), lymphopenia (1 patient), pathological fracture (1 patient) and middle otitis (1patient). Grade 4/5 AEs were not observed. Conclusions: The TP therapy would be tolerable for Japanese patients. We will report updated results at the meeting.