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The p53 gene is inactivated by the human papillomavirus (HPV) E6 protein in the majority of cervical cancers. Treatment of HeLa S3 cells with siRNA for HPV E6 permitted adenovirus-mediated transduction of a p53 gene linked to an upstream estrogen response element (ERE). Our previous study in non-siRNA treated HHUA cells, which are derived from an endometrial cancer and express estrogen receptor β, showed enhancing effects of an upstream ERE on adenovirus-mediated p53 gene transduction. In HeLa S3 cells treated with siRNA for HPV E6, adenovirus-mediated transduction was enhanced by an upstream ERE linked to a p53 gene carrying a proline variant at codon 72, but not for a p53 gene with arginine variant at codon 72. Expression levels of p53 mRNA and Coxsackie/adenovirus receptor (CAR) mRNA after adenovirus-mediated transfer of an ERE-linked p53 gene (proline variant at codon 72) were higher compared with those after non-ERE-linked p53 gene transfer in siRNA-treated HeLa S3 cells. Western blot analysis showed lower β-tubulin levels and comparatively higher p53/β-tubulin or CAR /β-tubulin ratios in siRNA-treated HeLa S3 cells after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with those in non-siRNA-treated cells. Apoptosis, as measured by annexin V binding, was higher after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with that after non-ERE-linked p53 gene transfer in siRNA-treated cells.

Background In the plasma of an advanced cancer patient, fibrinogen is sometimes increased with possible effects on red blood cells (RBCs). Materials and methods The plasma fraction deteriorating osmotic resistance of RBCs was separated from a patient's plasma with advanced ovarian cancer by phenyl-sepharose column chromatography and analyzed with gel filtration chromatography. Results In the plasma fraction, we found a protein reactive against whole fibrinogen with a molecular weight higher than that of intact fibrinogen from a healthy volunteer. The-high molecular weight protein was immunoractive to an antibody against fibrinogen gamma chain but not to an antibody against alpha or beta chain. Complement factor H, identified by N-terminal sequencing of a 150-kDa protein separated from the protein, was also eluted from anti-fibrinogen gamma immunoaffinity column. Conclusion Fibrinogen gamma chain and complement factor H were found to be bound as a protein complex in the plasma of a patient with advanced ovarian cancer.

Whilst most uterine smooth muscle neoplasms are benign, uterine leiomyosarcoma (Ut-LMS) is extremely malignant with a high incidence of metastasis and recurrence. Gynecological tumors are often associated with female hormone secretion, but no strong link has been detected between human Ut-LMS and the hormonal environment. In fact, the risk factors for Ut-LMS are poorly understood. In addition, no diagnostic biomarkers for differentiating between leiomyoma, a benign tumor, and malignant Ut-LMS have been found. Interestingly, mice that were homozygously deficient for LMP2/β1i were found to spontaneously develop Ut-LMS and exhibited a Ut-LMS prevalence of ~40% by 14 months of age. Thus, analyzing potential risk factors for Ut-LMS (such as LMP2/β1i) might aid the development of diagnostic biomarkers and clinical treatments for the condition.Fifty-seven patients (age range: 32-83 years) who had been diagnosed with uterine mesenchymal tumors were chosen from a pathological archive. Tissue samples from these patients were fixed in 10% buffered formalin, incubated in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections were stained with hematoxylin and eosin for standard histological examination or were subjected to further processing for immunohistochemical (IHC) examination. Serial Ut-LMS, bizarre leiomyoma, leiomyoma, and myometrium sections were subjected to IHC staining of β-smooth muscle actin, estrogen receptor, cyclin B1, LMP2/β1i, calponin h1, ki-67, tumor protein p53, and progesterone receptor.The Ut-LMS samples were positive for cyclin B1 and negative for LMP2/β1i, while the opposite result was obtained for bizarre leiomyoma, leiomyoma, and myometrium samples.The expression pattern of LMP2/β1i and cyclin B1 might be a diagnostic biomarker for human Ut-LMS. Studies of the biological roles of LMP2/β1i and/or cyclin B1 could lead to the elucidation of new targets for therapies against Ut-LMS.

Sarcomas are neoplastic malignancies that typically arise in tissues of mesenchymal origin. The identification of novel molecular mechanisms leading to sarcoma formation and the establishment of new therapies has been hampered by several critical factors. Human uterine leiomyosarcoma (Ut-LMS) develops more frequently in the muscle tissue layer of the uterine body than in the uterine cervix. Although the development of gynecologic tumors is often correlated with the secretion of female hormones; that of human Ut-LMS does not and its risk factors remain unknown. Importantly, a diagnostic biomarker that can distinguish malignant Ut-LMS from benign tumor uterine leiomyoma (LMA) has yet to be established. Therefore the risk factor(s) associated with human Ut-LMS to establish a diagnosis and novel therapeutic method. Proteasome b-ring subunit LMP2/b1i-deficient mice spontaneously develop Ut-LMS, with a disease prevalence of ~40% by 14 months of age. We shown that LMP2/b1i expression was absent in human Ut-LMS, but present in other human uterine mesenchymal tumors including uterine LMA. Therefore, defective-LMP2/b1i expression may be one of the risk factors for human Ut-LMS. LMP2/b1i is a potential diagnostic biomarker for human Ut-LMS, and may be a targeted-molecule for a new therapeutic approach.

We report a patient who has maintained a regular menstrual cycle despite undergoing cystectomy and chemotherapy for contralateral recurrence of ovarian immature teratoma with gliomatosis peritonei. We initially performed a fertility-sparing right salpingo-oophorectomy, omentectomy and peritoneal biopsy for immature teratoma with gliomatosis peritonei, with adjuvant chemotherapy; we performed a left ovarian cystectomy and peritoneal biopsy for mature cystic teratoma with gliomatosis peritonei 16 months after the first surgery, a fertility-sparing left ovarian cystectomy and peritoneal biopsy for contralateral recurrence of ovarian immature teratoma with gliomatosis peritonei 60 months after the first surgery, and a left ovarian cystectomy and peritoneal and external iliac lymph node biopsy for endometrial cyst with gliomatosis peritonei 71 months after first surgery. The peritoneal gliomatosis lesions gradually decreased through the 4 surgeries over 8 years. The patient has maintained a regular menstrual cycle and currently shows no evidence of disease.

Background: RNA-binding motif protein 10 (RBM10), originally identified as S1-1 protein, is a nuclear protein with likely functions in transcription and RNA splicing. The RBM10 gene maps to the X chromosome and, in female cells, is inactivated in one of the two X chromosomes near the boundary with genes escaping inactivation. This study investigated the occurrence of the RBM10 gene product in complete hydatidiform mole, which is composed of cells with paternal diploid chromosomes (46, XX). Methods: Deparaffinized normal chorion or complete hydatidiform mole tissues were hybridized with a fluorescein-conjugated RBM10 gene probe in fluorescent in situ hybridization (FISH) analysis. Immunohistochemistry and immunoelectron microscopy of the tissues were performed using an anti-RBM10 antiserum. Proteins from complete hydatidiform mole tissues and those separated by anti-RBM10-linked affinity chromatography were also examined by western blotting. Results: As expected, the RBM10 gene was detected by FISH as double spots in the nuclei of complete hydatidiform mole cells. Immunohistochemistry revealed a nuclear presence of RBM10 in normal chorion and complete hydatidiform moles, and a notable cytoplasmic presence in complete hydatidiform moles. Western blotting and immunoaffinity chromatography revealed that a 50 kDa protein was predominantly found in the cytosolic fraction of complete hydatidiform moles. Conclusions: A 50 kDa protein with common antigenicity to RBM10 was found in the cytoplasm of complete hydatidiform mole cells, and could represent one of the characteristics of the disease.

The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance.

The aim of the present study was to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with Müllerian carcinoma treated at our hospital. Nineteen patients with platinum-resistant Müllerian carcinoma were treated with intravenous PLD 50 mg/m(2) every 4 weeks. Tumor response was assessed by MRI following every 2-3 cycles of treatment. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (v3.0). The best overall responses in the 19 patients were identified as 5 partial responses (PR), 6 stable diseases (SD) and 8 progressive diseases (PD). Response rate was 26.3%. The proportion of patients with CR, PR or SD was 57.9%. The median time to progression was 188.0 days. The median survival time was 381.0 days. Toxicity grades were identified as one grade III hand-foot syndrome, two grade III neutropenia, one grade IV hand-foot syndrome, one grade IV stomatitis and one grade IV neutropenia. The present study confirmed that PLD is an effective drug when administered as a salvage therapy for the treatment of Müllerian carcinoma and is associated with a reduced toxicity profile compared with current therapeutic options.

Uterine leiomyosarcoma (Ut-LMS) develops more often in the muscle tissue layer of the uterine body than in the uterine cervix. The development of gynecologic tumors is often correlated with female hormone secretion; however, the development of Ut-LMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Importantly, a diagnostic-biomarker which distinguishes malignant Ut-LMS from other uterine mesenchymal tumors including leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with Ut-LMS, to establish a clinical treatment method. Proteasome subunit, low-molecular mass polypeptide(LMP2)/b1i-deficient mice spontaneously develop Ut-LMS, with a disease prevalence of ~40% by 14 months of age. Recent experiments with human and mouse uterine tissues revealed defective LMP2/b1i expression in human Ut-LMS that was traced to the interferon (IFN)-g pathway and a specific effect of Janus kinase (JAK)-1 somatic mutations on LMP2/b1i transcriptional activation. Furthermore, analysis of a human Ut-LMS cell line clarified the biological significance of LMP2/b1i in malignant myometrium transformation and the cell cycle, thus implicating LMP2/b1i as an anti-tumorigenic candidate. Therefore, defective-LMP2/b1i expression may be a risk factor for human Ut-LMS. LMP2/b1i is a potential diagnostic-biomarker for Ut-LMS, and may be a targeted-molecule for a new clinical therapeutic approach.

Mitotic-arrest deficiency 2 (MAD2) is a key component of spindle assembly checkpoint (SAC) function; SAC mediates spindle microtubule attachment to kinetochores on chromosomes and chromosomal segregation during mitosis. To determine whether MAD2 expression is associated with chemotherapy resistance in ovarian serous adenocarcinoma, we reviewed tumor samples from 41 cases of ovarian serous adenocarcinoma at Osaka City University Medical School Hospital (Osaka, Japan), 2000-2007. Of the 41 cases, 24 were recurrent and 17 were not recurrent. Expression of MAD2 was investigated in paraffin-embedded sections using a MAD2 antibody. Quantitative analysis of MAD2 expression gave mean weighted scores of 4.3 for the relapsed group and 7.2 for the relapse-free group; the expression was, thus, significantly greater in the relapse-free group compared to the relapsed group (P=0.023). When the 41 cases were classified into low- and high-expression, these classifications showed no significant difference in terms of progression-free survival (P=0.0685), however, overall survival for the low-expression group was significantly shorter than that of the high-expression group (P=0.0188). The present study implies that MAD2 expression levels can indicate sensitivity to anticancer agents, and risk for recurrence.

Uterine leiomyosarcoma (LMS) is a highly metastatic smooth muscle neoplasm for which calponin h1 is suspected to have a biological role as a tumor-suppressor. We earlier reported that LMP2-null mice spontaneously develop uterine LMS through malignant transformation of the myometrium, thus implicating this protein as an anti-tumorigenic candidate as well. In the present study, we show that LMP2 may negatively regulate LMS independently of its role in the proteasome. Moreover, several lines of evidence indicate that although calponin h1 does not directly influence tumorigenesis, it clearly affects LMP2-induced cellular morphological changes. Modulation of LMP2 may lead to new therapeutic approaches in human uterine LMS., Article, FEBS LETTERS. 586(13):1824-1831 (2012)

Objectives To investigate time intervals of ductus venosus (DV) flow velocity waveforms (FVW) in correlation to fetal heart rate and gestational age and to construct reference ranges for the second and third trimester. Furthermore, we investigate time intervals of FVW through the tricuspid valve. Methods Flow velocity waveforms of the DV and through the tricuspid valve were recorded in 135 normal singleton fetuses between 17 and 38 weeks' gestation. Time intervals for systolic (S) and early diastolic (D) peaks were analyzed regarding acceleration time (acc-S for S, acc-D for D) and deceleration time (dec-S for S, dec-D for D), respectively. Similarly, time intervals for both peaks of right ventricular inflow were analyzed regarding acceleration time (acc-E for E-wave, acc-A for A-wave) and deceleration time (dec-E for E-wave, dec-A for A-wave), respectively. Results In the DV, acc-D and dec-D increased significantly with gestational age. In tricuspid valve, acc-E and acc-A showed a significant increase with gestational age. All parameters except acc-S showed significant negative correlations with fetal heart rate. Conclusion With advancing gestational age, prolongation of the diastolic phase of DV-FVW and of the E-wave of tricuspid flow was observed, suggesting maturation of ventricular diastolic function. Time-related analysis of Doppler signals of DV-FVW may provide detailed insights into fetal cardiac function. © 2012 John Wiley & Sons, Ltd.

Maternal nutritional status during pregnancy is an important determinant of fetal growth. Although the effects of several nutrients and foods have been well examined, little is known about the relationship of overall maternal diet in pregnancy to fetal growth, particularly in non-Western populations. We prospectively examined the relationship of maternal dietary patterns in pregnancy to neonatal anthropometric measurements at birth and risk of small-for-gestational-age (SGA) birth among 803 Japanese women with live-born, singleton, term deliveries. Maternal diet in pregnancy was assessed using a validated, self-administered diet history questionnaire. Dietary patterns from thirty-three predefined food groups (g/4184 kJ) were extracted by cluster analysis. The following three dietary patterns were identified: the ‘meat and eggs’ (n 326), ‘wheat products’, with a relatively high intake of bread, confectioneries and soft drinks (n 303), and ‘rice, fish and vegetables’ (n 174) patterns. After adjustment for potential confounders, women in the ‘wheat products’ pattern had infants with the significantly lowest birth weight (P = 0·045) and head circumference (P = 0·036) among those in the three dietary patterns. Compared with women in the ‘rice, fish and vegetables’ pattern, women in the ‘wheat products’ pattern had higher odds of having a SGA infant for weight (multivariate OR 5·2, 95 % CI 1·1, 24·4), but this was not the case for birth length or head circumference. These results suggest that a diet high in bread, confectioneries, and soft drinks and low in fish and vegetables during pregnancy might be associated with a small birth weight and an increased risk of having a SGA infant.

Background: Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma is extremely malignant, with high rates of recurrence and metastasis. The development of gynecologic tumors is often correlated with secretion of female hormone; however, the development of human uterine leiomyosarcoma is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic-biomarker, which distinguishes malignant human uterine leiomyosarcoma from benign tumor leiomyoma is yet to be established. Aims : It is necessary to analyze risk factors associated with human uterine leiomyosarcoma, in order to establish a diagnostic-biomarker and a clinical treatment method. Patients and Methods : Histology and Immunofluorescence Staining: Uteri obtained from LMP2 -/- mice or its parental mice (C57BL/6 mice) were fixed in 10% buffered formalin, incubated in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections (5 μm) were prepared and stained with H&E for routine histological examination or were processed further for immunofluorescence staining with appropriate antidodies. Furthermore, a total of 101 patients between 32 and 83 years of age and diagnosed as having smooth muscle tumors of the uterus were selected from pathological files. Immunohistochemistry staining for LMP2 was performed on serial human uterine leiomyosarcoma, leiomyoma and myometrium sections. Results : Homozygous deficient mice for a proteasome β1i subunit, LMP2 spontaneously develop uterine leiomyosarcoma, with a disease prevalence of ~40% by 14 months of age. Defective LMP2 expression in human uterine leiomyosarcoma was demonstrated, but present in human leiomyoma and myometrium. Conclusions : Loss in LMP2 expression may be one of the risk factors for human uterine leiomyosarcoma. LMP2 may be a potential diagnostic-biomarker and targeted-molecule for a new therapeutic approach.

Sarcomas are a rare form of malignant tumor, with less than 15,000 new cases being diagnosed each year in the United States. In spite of their rarity, sarcomas are highly debilitating malignancies that are often associated with significant morbidity and mortality. They are also biologically very heterogeneous because they originate from many different tissues and cell types. Sarcomas have classically been defined by their tissue of origin and are additionally stratified according to their histopathology or the age of the patient at diagnosis. Uterine mesenchymal tumors that develop in the myometrium have traditionally been divided into benign uterine usual LMA, cellular LMA and malignant Ut-LMS based on cytological atypia, mitotic activity and other criteria. Ut-LMS is relatively rare, having an estimated annual incidence of 0.64 per 100,000 women [1], and is resistant to chemotherapy and radiotherapy; therefore, surgical interventions are virtually the only means of treatment [2, 3]. The prognosis of patients with Ut-LMS is poor, and the 5-year survival rate is approximately 35%. Uterine LMA may occur in 70-80% of women by the age of 50 years [4]. Difficulties have been reported in distinguishing Ut-LMS from other uterine mesenchymal tumors including uterine LMA, and a diagnosis generally requires surgery and cytoscopy. Diagnostic categories for uterine mesenchymal tumors and morphological criteria are used to assign cases. The non-standard subtypes of uterine mesenchymal tumors such as the epithelioid and myxoid types are classified in a different manner using these features; therefore, a diagnostic method needs to be established that can identify non-standard smooth muscle differentiation [5, 6]. High estrogen levels have been shown to significantly influence the development of tumors in the uterine body [7]. However, the molecular mechanisms underlying the transformation of uterine LMA and development of Ut-LMS remain unknown. Tumors that have developed and grown in the myometrium increase in size due to the influence of the female hormone, estrogen, which leads to the generation of more tumors. However, a relationship has not yet been reported between the development of Ut-LMS and hormonal conditions, and no obvious risk factors have been identified. The identification of risk factors associated with the development of human Ut-LMS will contribute significantly to the development of preventive and therapeutic treatments. Cytoplasmic proteins are mostly degraded by a protease complex referred to as the 20S proteasome, which has many substrates that consist of twenty-eight 20 to 30 kDa subunits [8, 9]. Proteasomal degradation is essential for many cellular processes, including the cell cycle, regulation of gene expression and immunological function [10]. A previous study reported that an interferon (IFN)-γ treatment induced the expression of large numbers of responsive genes, the β-ring subunits of proteasomes, i.e., low-molecular mass polypeptide (LMP)2/β1i, LMP7/β5i and LMP10/multicatalytic endopeptidase complex-like (MECL)-1/β2i [11]. Ut-LMS was detected in female LMP2/β1ideficient mice at 6 months or older, and its incidence at 14 months was approximately 40% [12]. Histopathological studies of LMP2/ β1i-lacking uterine tumors have revealed the characteristic abnormalities of Ut-LMS [12]. The non-standard subtypes of uterine mesenchymal tumors such as the epithelioid and myxoid types have been classified in a Manuscript accepted for publication May 15, 2014

Aim: The effects of transcervical microwave myolysis at 2.45 GHz after microwave endometrial ablation for menorrhagia were examined in patients with myomas. Methods: A transcervical microwave irradiation system assisted by transvaginal ultrasonic guidance was developed. Ten patients waiting for microwave endometrial ablation for menorrhagia caused by myomas entered the study after complete informed consent was obtained. Their outcomes were examined at least 6 months after transcervical microwave myolysis using the system. After completion of microwave endometrial ablation, interstitial microwave irradiation was performed using a guiding needle set in a puncture adaptor attached to a transvaginal ultrasonic probe and a microwave applicator of 1.6 mm in diameter. Shrinkage of the myoma was measured at 3 months and ≥6 months after the operation. Results: In nine patients with typical myomas, the major part consisting of a submucous or an intramural node 4.0–7.5 cm in size was necrotized. The typical myomas had shrunk by 41–68% at 3 months and 37–69% at ≥6 months after the operation. In one patient with a 6.8-cm cellular leiomyoma, necrosis was limited to the neighborhood of the applicator tip. Shrinkage was 17% at both 3 and 6 months. This patient required a second microwave endometrial ablation at 6 months to treat recurrent menorrhagia. None of the patients underwent hysterectomy after the treatment. No remarkable complications were encountered. Conclusions: Typical myomas shrink after microwave myolysis following microwave endometrial ablation. Transcervical microwave myolysis seems to be applicable as a low-invasive treatment for a typical myoma.

Purpose The effects of formaldehyde (FA) exposure on allergic disorders are not clearly understood. This cross-sectional study examined the relationship between FA exposure and the prevalence of allergic disorders in Japan. Metohds Subjects were 998 pregnant women. Participants were considered to have asthma, atopic eczema, or allergic rhinitis (including cedar pollinosis) if they had received any medical treatment for any of these allergic disorders during the previous 12 months. Passive air sampling tubes were worn for 24 hours and analyzed for FA. Results When FA levels were categorized into four groups, there was a tendency for a positive exposure-response relationship between FA levels and the prevalence of atopic eczema, although the adjusted odds ratio for highest vs. lowest FA categories did not reach statistical significance. When FA levels were categorized into two groups to assess the effects of exposure to high levels of FA on allergic disorders, FA levels of 47 ppb or more were independently associated with an increased prevalence of atopic eczema (adjusted odds ratio = 2.25; 95% confidence interval, 1.01–5.01). The positive association was more pronounced in women with a negative familial allergic history than in those with a positive familial allergic history. No clear association was found between FA levels and the prevalence of asthma or allergic rhinitis. Conclusions FA exposure may be associated with an increased prevalence of atopic eczema in Japanese pregnant women.

Chronic pelvic pain is a common and significant disorder among women. However, its etiology is not clear, and effective treatments remain inconclusive. The present study was designed to investigate the efficacy of antidepressants and Kampo medicines, which have been applied for other pain disorders, to treat chronic pelvic pain in women. Twenty-nine gynecological outpatients received pharmacological treatments. None of the patients had clear organic abnormalities that could explain their pain, nor did they have menstruation-related disorders. After considering severity of pain and clinical and psychosocial conditions for each patient, the medication and its administration was determined. Pain severity decreased in patients with antidepressants, which have been demonstrated to alleviate general chronic pain modulating through the descending pain inhibitory system. Kampo medicines such as Shuji-bushi, Sanyaku and Takusha also mitigated pain in patients. Our findings suggest that chronic pelvic pain, especially vulval pain, is difficult to treat, but administration of appropriate medication is effective and adjuvant analgesics could eliminate the symptoms. The present study further implies that a suitable pharmacological therapy, together with a psychological one–if necessary–is crucial in effectively treating chronic pelvic pain, which might induce depression and, ultimately, deteriorate quality of life.

To review clinical outcomes and therapeutic varieties, we were invited to submit data from the patients who were treated for uterine sarcomas in Japan from 1990 to 2003. Uterine sarcomas were defined as leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and carcinosarcoma (CS). Of a total of 97 patients, 36 (37.1%) were diagnosed with LMS of the uterine corpus, 15 (15.5%) with ESS, 46 (47.4%) with CS. Median age at diagnosis was 59 (21–85) years. Clinical stages based on FIGO were 41 (42.3%) with stage I disease, 6 (6.2%) with staged II, 34 (35.1%) with stage III, and 16 (16.5%) with stage IV. The median follow-up period for all patients was 13 (1–108) months and median disease-free period was 9 (0–96) months. The 1-year survival rate and disease-free survival (DFS) rate were calculated in patients with all sarcomas (overall survival [OAS], 61.3%; DFS, 46.6%). Statistical analysis showed that younger age (less than 50 years), early stage (stages I and II), and surgical procedure (extended hysterectomy [EH] and radical hysterectomy [RH]) were associated with significantly better OAS. Histologic types did not affect the survival period. In conclusion, aggressive surgery including EH or RH at the time of initial operation offers the possibility of prolonged survival.

Background: Insulin-lowering agents are reported to be useful in treating polycystic ovary syndrome (PCOS) anovulation. It has been suggested that lower insulin levels secondarily affect ovarian tissue, although the direct mechanism of action has not yet been verified. Here we investigated if these agents directly affect the ovary. Methods: Thirty female Wister rats were studied. Six control rats were injected subcutaneously with 0.2 ml sesame oil, while 24 rats used as PCOS models were injected subcutaneously with dehydroepiandrosterone (DHEA) and divided into four groups. Six rats were injected with only DHEA, while the remaining 18 rats received metformin, pioglitazone or troglitazone. The ovaries were immunohistochemically stained with anti- testosterone and anti-17β-HSD antibodies, and then evaluated for morphological changes. Results: In the DHEA administration group, the number of atretic follicles significantly increased compared to that of control rats. The insulin-lowering agents did not improve the multicystic appearance. Serum testosterone concentrations significantly increased with DHEA administration, but the increase was inhibited by oral administration of insulin-lowering agents. Testosterone deposits in ovarian tissue were also reduced by feeding rats insulin-lowering agents. Conclusion: Insulin-lowering agents affected ovarian tissue by inhibiting testosterone biosynthesis in vivo.

Aim: To examine the feasibility of microwave endometrial ablation (MEA), using a curved microwave applicator, in patients with menorrhagia caused by a submucous myoma greater than 3 cm in diameter, which is among the contraindications for conventional endometrial ablation. Methods: Patients included were refractory to medication, more than 45 years of age, and due to undergo hysterectomy to treat menorrhagia as a result of submucous myomas, although they hoped to avoid hysterectomy. Three patients underwent MEA at 2.45 GHz using a curved microwave applicator and microwave tissue coagulator to treat menorrhagia. Patients 1, 2 and 3 had submucous myoma nodes 4.5, 5.0 and 13 cm in diameter respectively. The applicator was guided under transabdominal ultrasonography to microwave irradiation sites arranged to cover the entire uterine lining based on preoperative magnetic resonance images. MEA was performed under general anesthesia or spinal anesthesia. Microwaves were irradiated at 40 W for 50 s for single irradiation sites. Results: Patient 1 became amenorrheic after the second MEA, which was performed 2 months after the first operation. Patients 2 and 3 became amenorrheic after the first MEA. Postoperative abdominal pain was controllable by a suppository of non-steroidal anti-inflammatory drugs. The patients were discharged the day after the operation. No remarkable complications were encountered during or after surgery. Conclusion: Microwave endometrial ablation improves menorrhagia caused by large submucous myomas when the microwave applicator reaches all parts of the uterine cavity.

Tetrahydrobiopterin (BH4) is a highly bioactive pterin required for nitric oxide synthase and monooxygenases of aromatic amino acids, and is involved in the synthesis of nitric oxide, catecholamines and Serotonin. Although these functions imply that pterin metabolism plays critical roles in human development, the intrauterine metabolism is unclear. To elucidate the pterin metabolism in the human feto-placental unit, blood was obtained from the umbilical artery and vein, and the maternal vein, and plasma biopterin and neopterin concentrations were analyzed by the high-performance liquid chromatography method. To clarify the effect of labor, data was also compared between the transvaginal delivery (TV) and the caesarean delivery (CS). The levels of biopterin and the neopterin, and neopterin/biopterin ratio were higher in the fetal plasma than in the maternal plasma. Biopterin levels in the umbilical artery were higher than those in the umbilical vein. There were significant correlations in either biopterin or neopterin between the fetal plasma and the maternal plasma. There was no significant difference in the fetal pterin levels between TV and CS. The results suggest the stimulated BH4 synthesis in the fetoplacental unit, the independent homeostasis of the fetal pterin metabolism, and the possibility of dynamic movements of pterins among the fetus, the placenta and the mother.

Background: Patients with cervical cancer who develop pelvic recurrence after primary surgery are usually treated with radiation-based therapy. However, their prognoses are dismal. We conducted a phase I study of combined radiation, hyperthermia and intra-arterial (IA) carboplatin for local recurrence of cervical cancer. Patients and methods: Patients with local recurrence of cervical cancer without extrapelvic recurrence were included in this study. Carboplatin was given as a 5-min IA infusion without hydration just before pelvic radiation every day. External pelvic irradiation (1.8 Gy/day for 28 days) was performed according to local standard schedules. After 20 Gy had been administered, hyperthermia was performed once a week with a radio frequency heating system for four cycles. Results: Fifteen patients were entered through the four dose levels of carboplatin. The maximum tolerated dose was determined to be 25 mg/m2 and the dose-limiting toxicities were leukocytopenia, neutrocytopenia and diarrhea. Grade 3/4 leukocytopenia and diarrhea were observed in nine (60%) and three (20%) of 15 patients. Tumor responses included five complete responses and nine partial responses, and the overall response rate was 93.3% (14 of 15) (95% confidence interval 59.4% to 100%). Tumor reductions were observed only at 20 Gy in 10 cases of 14 responders (71.4%). Conclusion: The combination therapy of radiation, hyperthermia and IA carboplatin is safe and well-tolerated for locally recurrent cervical cancer.

Objective: To describe a practical procedure of transcervical needle biopsy of uterine myoma-like tumors using an automatic biopsy gun and its potential risks. Design: Description of new biopsy procedure. Setting: University teaching hospital. Patient(s): Three hundred twelve patients who had been recommended for surgery for uterine myoma-like tumors by the hospital's outside doctors. Intervention(s): Transcervical needle biopsy of uterine myoma-like tumors. Main Outcome Measure(s): Successful sampling rate, duration of procedure, estimated blood loss, patient discomfort, and complications. Result(s): Of the 312 patients who underwent transcervical needle biopsy, specimens were obtained from 311 (99.7%). The mean (± SD) duration of procedure was 6.3 ± 5.2 minutes. The mean estimated blood loss was 10.4 ± 10.9 g. There were two cases (0.6%) in which the blood loss during the procedure was in excess of 50 g, but bleeding can be conservatively controlled in such cases with an intrauterine tamponade using gauze or a balloon catheter. The level of patient pain and discomfort during the needle biopsy was significantly lower than that during endometrial curettage. No major complications requiring surgery occurred. Conclusion(s): Transcervical needle biopsies of uterine myoma-like tumors using an automatic biopsy gun are practical, simple, and safe. This new procedure can be of routine clinical use.

BACKGROUND The clinical differential diagnosis between uterine sarcoma and benign leiomyoma is difficult even with magnetic resonance imaging (MRI). Therefore, a considerable number of patients have undergone hysterectomies due to an indication of “suspected malignancy” based on tumor size alone. However, approximately 80% of these hysterectomies have been judged to have been recommended inappropriately. In such situations, reliable preoperative diagnostic tests are required. The authors have evaluated the accuracy of needle biopsy for uterine myoma-like tumors, a procedure that to the authors' knowledge has been performed infrequently. METHODS Transcervical needle biopsy was performed in 435 patients with uterine myoma-like tumors. The biopsy specimens were scored for degree of malignancy according to the histopathologic criteria proposed by Bell et al. Histopathologic evaluation of surgical specimens and clinical outcome after 2 years of follow-up were used as the reference standards. RESULTS Of 435 patients, 7 had uterine sarcomas, 4 of which were scored as ≥ 4 points and were diagnosed as “sarcoma” by needle biopsy alone. No sarcoma cases were included in the group of patients with a score of 0. The cutoff score combining the highest sensitivity and specificity with respect to distinguishing uterine leiomyosarcoma from uterine leiomyoma was 2; sensitivity, specificity, and positive and negative predictive values were 100%, 98.6%, 58%, and 100.0%, respectively. CONCLUSIONS Transcervical needle biopsy using histopathologic scoring is a reliable diagnostic test for the differential diagnosis between uterine sarcoma and leiomyoma. This diagnostic method, combined with MRI screening, could reduce the number of patients currently undergoing unnecessary surgery. Cancer 2002;94:1713–20. © 2002 American Cancer Society. DOI 10.1002/cncr.10382

Purpose: Evaluation of vascular endothelial growth factor (VEGF) concentrations of follicular fluid (FF) in accordance with an ovarian stimulation protocol and ovarian response. Methods: The subjects of this study were 38 patients undergoing IVF-ET in our hospital. They were divided into three groups according to ovarian stimulation protocols; Group 1: hMG cycles (n = 19), Group 2: clomiphene citrate cycles (n = 10), Group 3: natural cycles (n = 9). They reclassified into three groups according to the number of oocytes harvested. VEGF concentration was measured in FF, employing ELISAs. Results: Group 1 shows lower VEGF concentrations in FF than Group 2 or Group 3. Excluding high responders from Group 1, no difference was found among these three groups. As for the reclassified groups, group of highest number of oocytes havested showed lowest VEGF concentrations in FF. Conclusions: VEGF concentrations in FF might negatively correlate with the number of follicles, irrespective of the ovulation induction protocol.

Uterine leiomyosarcoma (Ut-LMS) more frequently develops in the muscle tissue layer of the uterine body than in the uterine cervix. The development of gynecological tumors is often correlated with the secretion of female hormones; however, the development of Ut-LMS has not been correlated with hormonal conditions, and risk factors remain unknown. A diagnostic biomarker that can distinguish malignant Ut-LMS from benign tumor leiomyoma (LMA) has not yet been established. Therefore, an analysis of the risk factors associated with human Ut-LMS is needed in order to establish a treatment method. Proteasome LMP2/β1i-deficient mice spontaneously develop Ut-LMS, with a disease prevalence of ~40% by 14 months of age. We found that the expression of LMP2/β1i was absent in human Ut-LMS, but present in human LMA. Therefore, the defective expression of LMP2/β1i may be one of the risk factors for Ut-LMS. LMP2/β1i is may be a potential diagnostic biomarker for human Ut-LMS, and may be a targeted molecule for a new therapeutic approach.

Disruptions of the p16-CDK4/cyclin D1-pRb pathway (RB pathway) and the p14ARF-MDM2-p53 pathway (p53 pathway) are important mechanisms in the development of human malignancies. In this study, we investigated RB and p53 pathways in 46 epithelial ovarian cancers (EOCs). In the RB pathway, 16 (34.8%) of 46 cases had p16 gene alterations or loss of expression. The deletion of the p16 gene was a rare event. In 7 cases, we observed methylation in the 5`CpG island in the promoter region of the p16 gene. Abnormal expressions of pRb and CDK4/cyclin D1 were 10.9% and 30.4%, respectively. In the p53 pathway, 10 (21.7%) of 46 cases had p14ARF gene alterations or abnormal expression. In 4 cases, methylation in the 5`CpG island in the promoter region of the p14ARF gene was present. MDM2 overexpression was a rare event. Thirty-six (78.3%) of 46 patients had p53 gene alterations or expression. In our studied cases, p14ARF abnormalities were independent of p16 abnormalities. Abnormal RB and p53 pathways were present in 60.9% and 80.4% of cases, respectively. In conclusion, disruptions of p53 and RB pathways are frequent events and the inverse correlations were present between the abnormality of p16 and p14ARF in EOCs. H UM P ATHOL 32:988-996. Copyright © 2001 by W.B. Saunders Company

The mechanism of weight loss induced by the growth of malignant tumors is still unknown. We investigated it by focusing on apoptosis of skeletal muscle. VX2-tumor was implanted into rabbits and the apoptotic index (AI) of skeletal muscle was measured by in situ end-labeling assay. Plasma of the tumor-bearing rabbits was perfused repeatedly through non-coated charcoal resin. The AI reached 54.6% early after tumor implantation, when weight loss amounted to an 18% decrease in lean body mass (LBM) without change in muscle DNA synthesis or urinary 3-methylhistidine / creatinine ratio (3-MH / Cr). When the decrease of LBM reached 30%, DNA synthesis was decreased by 48% and 3-MH / Cr was increased by 104%, whereas AI was only 4.7%. The plasma perfusion did not prevent apoptosis in muscle, but improved LBM, DNA synthesis, and 3-MH / Cr. There may be two mechanisms of muscle depletion during the tumor growth: apoptosis in the early stage and metabolic abnormalities in muscle in the late stage.

Haptoglobin (Hp) possesses many functions in the immune system and angiogenesis as well as scavenging released hemoglobin, and thus it is speculated that Hp may also play a critical role in the reproductive process. To investigate the possible involvement of Hp in the outcome of in vitro fertilization and embryo transfer (IVF-ET), the serum Hp of 50 patients who underwent IVF-ET was analyzed by the Western blot method. The results showed a higher pregnancy rate in the patients with the Hp2-2 phenotype (38%) than in those with the Hp2-1 phenotype (16%) (p = 0.08), and the serum α2 subunit levels in the patients who achieved pregnancy within four attempts at IVF-ET were higher than in the others (p < 0.05). The results of this study suggest that Hp is involved in the outcome of IVF-ET.

We reported finding that apoptosis occurred in skeletal muscle in the early stage after implantation. In the present study, we investigated expression of the apoptosis-related proteins Bax and Bcl-2 to determine the mechanism of the apoptosis. In the early stage of tumor bearing, 20 days after implantation, lean body mass (LBM) was reduced by 5.06 +/- 1.10% in the tumor-bearing group, compared with an increase of 4.96 +/- 1.26% in the control group. The apoptotic index (AI) of the skeletal muscle in the tumor-bearing group increased to 40.5 +/- 3.20% but was 0% in the control group, and Bax expression was strongly positive in 5 of the 10 rabbits in the tumor-bearing group, and significantly stronger than in the control group (P = 0.0002). In the late stage of tumor bearing, 40 days after implantation, the AI had declined to 0.93 +/- 0.96% in the tumor-bearing group, but was still 0% in the control group. Bax expression was rarely detected in either the tumor-bearing group or the control group, and there was no significant difference between the two groups (P = 0.706). No significant changes in Bcl-2 were observed in either group. The above results showed that apoptosis via Bax played a role in muscle wasting associated with progression of the malignant tumor. However, the apoptosis and expression of Bax were seen only in the early stage, within 20 days after implantation, not in the late stage. This suggested that the muscle wasting in the early stage might be caused by a different mechanism from that in the late stage.

Objective: To compare ultrastructural features of leiomyoma cells from the same uterine myoma nodule before and after GnRH agonist (GnRH-a) treatment and to examine the relation between these ultrastructural changes and the extent of myoma volume reduction with GnRH-a treatment. Design: Prospective clinical study. Setting: University teaching hospital. Patient(s): Twenty women with uterine leiomyomas who were scheduled for surgery. Intervention(s): Transcervical needle biopsy of uterine myoma, s.c. leuprolide acetate injection (3.75 mg) at least three times every 4 weeks before surgery, and hysterectomy or myomectomy. Main Outcome Measure(s): The changes in ultrastructural features of uterine leiomyoma cells and the percentage decrease in the volume of the largest myoma at 12 weeks of GnRH-a treatment measured by magnetic resonance imaging. Result(s): A decrease in myofilaments, mitochondrial swelling, and emergence of the lysosomal body were observed in relation to GnRH-a treatment. Furthermore, a positive correlation was observed between the decrease in myofilaments and myoma shrinkage. Conclusion(s): Cellular atrophy due to a decrease in myofilaments plays a major role in the reversible myoma shrinkage resulting from GnRH-a treatment.

Objective: Our purpose was to determine whether the urinary incontinence (UI) score is significantly useful in evaluating the clinical status of UI. Method: The questionnaire was administered to 198 UI patients (27–73 years of age) diagnosed by conventional procedures. It consisted of 15 questions, and the answers were assigned points divided into a stress score (s-s) and urge score (u-s) according to severity. Results: The patients were classified into a stress incontinence group (SI; 125 cases), urge incontinence group (URI; 29 cases), mixed incontinence group (MI; 41 cases), and overflow incontinence group (3 cases). Classification by questionnaire yielded 110 SI cases, 31 URI cases, and 46 MI cases, accuracy of 83.2%, 86.2%, and 61.0%, respectively. A significant correlation was observed with s-s of SI (r=0.669, P

The purpose of this study was to investigate the clinical application of a microwave tissue coagulator at 2.45 GHz with a needle electrode specifically customized for endometrial ablation. Endometrial ablation was performed under intravenous thiopental anesthesia on three women suffering from hypermenorrhea caused by aplastic anemia (two), von Willebrand's disease (one) using a microwave tissue coagulator at 2.45 GHz. All patients were amenorrheic after endometrial ablation. No notable complications were observed during or after endometrial ablation. Endometrial ablation using a microwave tissue coagulator at 2.45 GHz is a simple and efficacious method for the treatment of hypermenorrhea.

The hematologic data and symptoms of 7 patients seropositive for parvovirus B19 IgM antibody after gynecologic surgery were analysed. Parvovirus may have been transmitted by fibrin glue prepared from heat-treated human plasma and used for hemostasis during surgery. The peripheral blood neutrophil count decreased to below 1 × 109/l between postoperative day (POD) 10 and 18, but recovered spontaneously to within the normal range. G-CSF injection was effective in preventing neutropenia or obtaining a prompt recovery. The reticulocyte count fell below 10 × 109/l between POD 13 and 19, and also recovered spontaneously. A slapped-cheek rash was not observed in any of the 7 patients.

Vaginal total hysterectomy with vaginal plasty was performed in 107 patients with pelvic organ prolapse. The posterior urethrovesical angle (PUVA) was measured by chain urethrocystography. Bladder capacity, residual and incontinence urine volume were measured before and after surgery, and the data obtained were analyzed in relation to postoperative improvement and recurrence of urinary dysfunction. There were no significant differences between the background of patients with dysuria, incontinence, a mixture of dysuria and incontinence, and neither of these symptoms. Postoperative incontinence and residual urine volume decreased in all groups. However there was no correlation between the preoperative PUVA and either incontinence or residual urine volume. Measurement of PUVA was neither helpful in making the diagnosis nor predictive of the recurrence of urinary dysfunction.

Changes in total body fat and the metabolic and morphologic characteristics of adipose tissue were sequentially investigated in individual rabbits implanted with VX2 tumors to elucidate the pathology of the fat reduction in animals with malignant tumors as compared with that of diet-restricted rabbits. Lipogenesis in normal, VX2-implanted, and diet-restricted rabbit groups on day 40 after the start of the experiments was 19.1 +/- 2.9, 13.3 +/- 3.5, and 41.7 +/- 6.0 x 10(5) cpm/g/h, respectively, and glycerol liberation by their adipose tissue was 199 +/- 21, 528 +/- 94, and 301 +/- 45 nmol/g/h, respectively. In addition, apoptotic cells were noted in the adipose tissue of VX2-implanted rabbits on days 20-30 after implantation, but not in diet-restricted rabbits. The results showed clear differences between the total body fat reduction profiles of VX2-implanted rabbits and diet-restricted rabbits, suggesting a characteristic lipid metabolism with enhanced lipolysis and diminished lipogenesis in VX2-implanted rabbits. The results strongly suggest that adipocyte apoptosis might be involved in these phenomena.

Anemia-inducing substance (AIS) is a protein of approximately 50,000 molecular weight secreted by malignant tumor tissue that depresses erythrocyte and immuno-competent cell functions; in this study, its biological effects on adipocytes were examined. Changes in body weight, total body fat, and food intake were investigated in rabbits after VX2 carcinoma transplantation, and the results showed reductions of 11%, 24%, and 30%, respectively, at 40 days after transplantation compared with baseline values (before transplantation). The values were even more markedly reduced 70 days after transplantation. When cyclic plasma perfusion (2 times/wk) was started at 40 days after transplantation, the values at 70 days after transplantation (30 days after beginning plasma perfusion) recovered to 91%, 84%, and 87%, respectively, of the baseline values. AIS fractions were isolated from rabbit plasma by using a phenyl-Sepharose column before transplantation, 40 and 70 days after transplantation, and 30 days after start of plasma perfusion, and AIS activity and lipolytic activity were measured. The results showed enhancement of AIS activity and lipolytic activity as the tumors grew. Lipolytic activity also returned to baseline value as AIS was removed by adsorption by plasma perfusion, and there was a high correlation between lipolytic activity and AIS kinetics. These results strongly suggest that AIS might be one of the substances involved in the enhanced lipolytic activity in advanced tumor-bearing subjects.

Intermittent cisplatin (CDDP) administration as consolidation therapy for stage-III ovarian cancer was studied. No patients with residual disease at surgery or at second-look operation or patients with 2 for 5 days was administered every 3–4 months for 5 years. A significant increase in 5-year survival rate was found in the intermittent chemotherapy group when compared with the control group. Side effects from the intermittent chemotherapy were controllable. Intermittent CDDP therapy seems to be an effective consolidation therapy for stage-III ovarian cancer patients.

Rabbits implanted with VX2 carcinoma and treated by cyclic plasma perfusion showed lower weight loss and longer survival than untreated rabbits. The urinary 3‐methylhistidine/creatinine ratio was less elevated in the treated rabbits than in the untreated rabbits. Myoblasts from untreated rabbits with VX2 carcinoma showed lower proliferation than those from normal rabbits, while those from rabbits treated by cyclic plasma perfusion showed intermediate proliferation. Furthermore, the DNA synthesis rate of myoblasts from treated rabbits was much better maintained than in the case of untreated rabbits.

A simple formula (1.536 × TOBEC + 475.146 = LBM, where TOBEC is total body electrical conductivity and LBM is lean body mass) to estimate LBM in grams was developed on the basis of the total body fat data obtained by ether extraction and TOBEC in normal rabbits. The formula was also applicable to rabbits with cachexia induced by inoculation of VX2 carcinoma or by starvation. We were able to assess the losses of body fat in the rabbits with cachexia at 10‐day intervals by using TOBEC.

Adenoma malignum (minimum deviation adenocarcinoma) is a rare neoplasma of the uterine cervix, the diagnosis of wich cannot be determined by cervical smear. Recently, magnetic resonance imaging (MRI) was reported as useful for its diagnosis, but differentiation of adenoma malignum from deep-seated nabothian cysts remains problematic. We report here a case of adenoma malignum of the uterine cervix, for which MRI findings could not neglect deep-seated nabothian cysts. However, transvaginal power Doppler ultrasonography clearly showed richness of small vessels, whose arterial flow had higher velocity in the diastolic phase, around the cystic lesion of the uterine cervix. These findings indicate that, at least in the case reported here, transvaginal power and pulsed Doppler ultrasonography is a useful tool for the diagnosis of adenoma malignum of the uterine cervix.

Mice transplanted with a cachexia-inducing colonic adenocarcinoma (MAC16) show a progressive decrease in liver glycogen in direct proportion to the loss of body weight. Such tumours elaborate a lipid mobilizing factor (LMF), which produces a dose-dependent stimulation, not only of adipocyte adenylate cyclase, but also of heptocyte adenylate cyclase in a GTP-dependent manner. These results suggest that LMF has the capacity to initiate hepatic glycogenolysis through an increase in cyclic AMP.

Copper transporters (CTR) also regulate the cellular transport of platinum drugs, but their role in platinum resistance of ovarian cancer has not been elucidated.CTR expression in ovarian cancer tissues resected from patients treated by platinum-based chemotherapy was evaluated immunohistochemically. CTR2 expression in ovarian cancer cells was inhibited by bathocuproine disulfonate, and the changes in cisplatin sensitivity were examined.CTR2 expression was increased in chemoresistant patients, but not significantly. However, the CTR2/CTR1 ratio was significantly increased in chemoresistant patients. Cases with positive CTR2 expression or positive CTR2/CTR1 ratio had poor prognoses. When the CTR2 expression in ovarian cancer cells was suppressed, sensitivity to cisplatin was significantly increased.These data suggest that CTR2 contributes to platinum resistance in ovarian cancer. The CTR2/CTR1 ratio is a useful marker for platinum sensitivity and a potential prognostic factor in patients with ovarian cancer.

An enlarged uterus of more than 12 cm in cavum length with a distorted cavity is a contra-indication for conventional ablative techniques. It is difficult to perform satisfactory endometrial ablation in a large uterus with submucosal myomas using straight instruments. A new curved microwave applicator 4 mm in diameter was developed for microwave endometrial ablation (MEA) for uteri with an enlarged distorted uterine cavity.For three patients of menorrhagia due to submucosal myomas with cavum lengths 13 to 15 cm, MEA was performed using the curved applicator.Menorrhagia was improved in each case. No complications were encountered.A large number of hysterectomies could be avoided using the new curved microwave applicator.

Objective The clinical management of atypical polypoid adenomyoma (APAM) of the uterus remains to be established. We collected APAM cases, reviewed the clinicopathological features, and discussed the clinical management. Methods Twenty-nine patients with APAM were identified by searching the tumor registry of the Japan Clinical Oncology Group (JCOG). Clinical information and histological specimens were obtained from 13 institutional members of the JCOG, and a central pathological review was performed. Results The mean age of the patients was 38years (range, 22–58). Squamous metaplasia was present in 19 cases (65.5%), and well-differentiated endometrioid adenocarcinoma coexisted in 5 cases (17.2%). Primary treatment consisted of dilatation and curettage in 9 patients (31.0%), vaginal resection in 2 patients (6.9%), hysteroscopic transcervical resection (TCR) using hysteroscopy in 10 patients (34.5%), and hysterectomy in 8 patients (27.6%). There were recurrences in 5 (23.8%) of the 21 cases in which fertility was preserved, and the recurrent rate was 10% (1/10) in patients those were treated with TCR and 36.4% (4/11) in those the other treatment options were selected. All patients were alive after primary treatment (a mean follow-up period was 39.6months; range, 1–202). Conclusion The clinical outcome of APAM is benign. However, differential diagnosis should be performed because of its histological similarity to invasive endometrial carcinoma and the possibility of coexistence with other endometrial neoplasms. TCR is a recommended diagnostic and treatment option for patients who desire to preserve fertility.

To investigate time intervals of ductus venosus (DV) flow velocity waveforms (FVW) in correlation to fetal heart rate and gestational age and to construct reference ranges for the second and third trimester. Furthermore, we investigate time intervals of FVW through the tricuspid valve.Flow velocity waveforms of the DV and through the tricuspid valve were recorded in 135 normal singleton fetuses between 17 and 38 weeks' gestation. Time intervals for systolic (S) and early diastolic (D) peaks were analyzed regarding acceleration time (acc-S for S, acc-D for D) and deceleration time (dec-S for S, dec-D for D), respectively. Similarly, time intervals for both peaks of right ventricular inflow were analyzed regarding acceleration time (acc-E for E-wave, acc-A for A-wave) and deceleration time (dec-E for E-wave, dec-A for A-wave), respectively.In the DV, acc-D and dec-D increased significantly with gestational age. In tricuspid valve, acc-E and acc-A showed a significant increase with gestational age. All parameters except acc-S showed significant negative correlations with fetal heart rate.With advancing gestational age, prolongation of the diastolic phase of DV-FVW and of the E-wave of tricuspid flow was observed, suggesting maturation of ventricular diastolic function. Time-related analysis of Doppler signals of DV-FVW may provide detailed insights into fetal cardiac function.

Objective To evaluate the clinical outcomes of traditional surgical approaches to pelvic organ prolapse. Methods From January 20, 2000, to March 24, 2009, 182 patients underwent traditional prolapse surgery at Osaka City University Graduate School of Medicine, Osaka, Japan, after prolapse assessment by the pelvic organ prolapse quantification system. Incontinence, defined as more than 2 g of urine leaked in a 1-hour pad test; posterior urethrovesical angle, using chain cystography; and quality of life (QOL), using a face visual analog scale, were assessed 1, 3, 6, and 12 months postoperatively, and then annually for 2 more years, in the 167 patients who completed follow-up. The presence of lower urinary tract symptoms was determined preoperatively and postoperatively. Results The anatomic and subjective recurrence rates were 21.0% and 6.0%. There was a significant difference in time to recurrence between anatomic and subjective prolapse. The posterior urethrovesical angle was improved postoperatively. The prevalence of lower urinary tract symptoms was 67.1% preoperatively and decreased to 28.2%, 17.2%, 16.2%, 15.6%, and 15.6% at 1 month, 6 months, 1 year, 2 years, and 3 years, respectively, and QOL was improved postoperatively regardless of anatomic recurrence. Conclusion Anatomic support and QOL were satisfactory after traditional prolapse surgery.

In this study, we compare the time to normalization of CA125 after cytoreductive surgery between a paclitaxel-containing regimen and a non-paclitaxel regimen. This study demonstrates that CA125 regression in a paclitaxel-containing regimen was slower than that in a non-paclitaxel regimen. When we determine the CA125 regression rate to predict overall survival in ovarian cancer, we should take into account the kind of chemotherapy regimen, especially the use of paclitaxel.