Pregnancy Outcomes After Abdominal Radical Trachelectomy for Early-Stage Cervical Cancer: A 13-Year Experience in a Single Tertiary-Care Center.

OBJECTIVE: To investigate pregnancy outcomes in women after abdominal radical trachelectomy (RT) for early-stage cervical cancer. METHODS: The patients' background, fertility, and pregnancy outcomes were reviewed in a total of 61 pregnancies in 48 of 172 women who underwent abdominal RT at Keio University Hospital between September 2002 and December 2013. RESULTS: There were 5 women with stage IA1, 2 with stage IA2, and 41 with stage IB1. Histological types were as follows: squamous cell carcinoma (n = 36), adenocarcinoma (n = 10), and adenosquamous cell carcinoma (n = 2). The pregnancy rate of women attempting to conceive after abdominal RT was 44% (48/109). The mean ± SD duration from abdominal RT to conception was 3.1 ± 1.9 years. Of 61 pregnancies, 42 pregnancies were achieved by fertility treatment (in vitro fertilization-embryo transfer, 39; intrauterine insemination, 3). After excluding one pregnancy without detailed clinical information, there were 42 live births (5 in 22-27 weeks, 11 in 28-33weeks, 20 in 34-36 weeks, and 6 in 37-38 weeks), 13 miscarriages, and 5 ongoing pregnancies. While there were 10 first trimester miscarriages, 3 pregnancies ended in the second trimester owing to chorioamnionitis. The mean gestational age at birth was 33 weeks of pregnancy. Thirty-seven neonates were appropriate-for-date, and one was small-for-date. Six pregnancies exhibited massive bleeding from the residual cervix in the late pregnancy. Preterm birth less than 34 weeks of pregnancy was related to premature rupture of the membrane (P < 0.05). Chorioamnionitis was evident in 9 of 11 pregnancies with preterm premature rupture of the membrane followed by birth at less than 34 weeks of pregnancy. No parturients exhibited lochiometra and endometritis postpartum. CONCLUSIONS: Abdominal RT provided favorable pregnancy outcomes, and fertility treatment could be advantageous to conception. Massive bleeding from the residual cervix as well as ascending infection might be characteristic features during pregnancy after abdominal RT.

Clinical impact of women with gestational diabetes mellitus by the new consensus criteria: two year experience in a single institution in Japan.

There is a paucity of information on perinatal data regarding gestational diabetes mellitus (GDM) by the new criteria from a real experience because the number of health care associations implementing the new criteria is still limited. The aim of this study is to investigate perinatal features of the new criteria-defined GDM. We reviewed a total of 995 women with singleton pregnancy that underwent GDM screening followed by a diagnostic oral glucose tolerance test (OGTT). All women found to have GDM underwent self-monitoring of blood glucose measurements as well as dietary management. Insulin treatment was initiated when dietary treatment did not achieve the glycemic goal. Of the 995 women, 141 had GDM (14.2%): 104 with one, 27 with two, and 10 with three abnormal OGTT values. Women with two or three abnormal OGTT values (2/3-AV) needed insulin treatment more frequently than those with one abnormal OGTT value (1-AV) (70.3% vs 23.1%, P < 0.0001). After adjustment for age, pregravid overweight, gestational weeks at diagnosis, a first-degree family history of diabetes was correlated with the implementation of insulin treatment in women with 1-AV (adjusted odds ratio 3.9; 95% Confidence Interval 1.7-9.2; P = 0.001). When compared perinatal outcomes between women with normal glucose tolerance and GDM, fetal growth and the occurrence of pregnancy-induced hypertension were comparable between the two groups. Our data suggest that the IADPSG-defined GDM with 1-AV show less severe glucose intolerance, but might be at risk of insulin requirement when a first-degree family history of diabetes exists.

Fetal stomach paracentesis in combined duodenal and esophageal atresia.

Fetuses with concomitant duodenal atresia (DA) and esophageal atresia (EA) might develop in utero gastric rupture as well as neonatal respiratory complication due to dilated stomach and duodenum. Our patient with the typical "double bubble" appearance was highly suspected to have DA in the second trimester. Follow-up examinations revealed a massively dilated stomach and duodenum with a dilated distal esophagus, indicating concomitant DA and EA. With advancing pregnancy, the fetal abdomen progressively increased in size by retention of fluid in the closed loop of DA and EA. To avoid gastric perforation, prenatal stomach paracentesis using an ultrasound-guided needle was performed three times until delivery. A male neonate born at 37 weeks gestation showed no respiratory complication. Perinatal clinical features and operative findings revealed combined DA and EA (gross type A). He was successfully managed with duodenoduodenostomy, followed by esophago-esophagostomy. On fetal sonography, the marked "double bubble" appearance and the cystic structure presenting peristalsis-like movement above the diaphragm were indicative of concomitant DA and EA. Fetal stomach paracentesis could contribute to the improvement of perinatal outcomes in fetuses with this pathological condition.

Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy.

High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

Comparison of the right and left ventricular performance during the fetal development using velocity vector imaging.

BACKGROUND: Studies on myocardial characteristics examined by speckle-tracking echocardiography are limited. AIMS: To compare myocardial performance between the right and left ventricles during the fetal development using velocity vector imaging (VVI). SUBJECTS AND STUDY DESIGN: Echocardiograms of 95 uncomplicated singleton fetuses (19-36 weeks pregnancy) were retrospectively analyzed by VVI to measure global longitudinal peak velocity, strain, and strain rate of both the right ventricle (RV) and left ventricle (LV). The regional values were calculated for three segments (base, mid, and apex) of the ventricular free wall and segment. OUTCOME MEASURES: The VVI-derived measurements were examined for gestational age and compared between ventricles. RESULTS: The global peak systolic and diastolic velocity values of both ventricles significantly increased over gestation examined, whereas the global systolic strain and strain rate were stable (RV: strain -22.6 ± 5.0%, strain rate -2.6 ± 0.7/s; LV: strain -21.5 ± 5.6%, strain rate -2.5 ± 0.7/s). Compared to the LV, the RV showed significantly higher global velocity in systole and diastole (P = 0.001 for systole, P < 0.001 for diastole). The global systolic velocity of the LV increased close to the RV toward term, whereas the RV was dominant in diastole throughout the examined gestation. Basal strain and strain rate in the RV were significantly greater than that of the LV, although there were no significant differences in the middle and apical values between ventricles. CONCLUSION: Our findings suggest the RV predominance of longitudinal contraction and dilatation, compared to the LV in uncomplicated fetuses.

Reproductive and obstetric outcomes after radical abdominal trachelectomy for early-stage cervical cancer in a series of 31 pregnancies.

STUDY QUESTION: What are the reproductive and obstetric outcomes in patients undergoing radical abdominal trachelectomy (RAT) for early-stage cervical cancer? SUMMARY ANSWER: When RAT was performed before a pregnancy achieved with fertility treatments, pregnancy rate of 36.2% was obtained and 71.4% of these women gave birth at ≥ 32 weeks of gestation. WHAT IS KNOWN ALREADY: Reproductive and obstetric outcomes after radical vaginal trachelectomy (RVT) are well documented; however, these outcomes after RAT have not been well studied. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study of patients at a single institution who underwent RAT and became pregnant. Reproductive and obstetric outcomes of 114 patients who had undergone RAT from September 2002 to December 2010 were investigated. PARTICIPANTS/MATERIAL, SETTING, METHODS: Women of reproductive age with early-stage cervical cancer who wished to preserve their fertility were documented. MAIN RESULTS AND THE ROLE OF CHANCE: Patients' median age was 33 years (25-40 years). A total of 31 pregnancies were achieved in 25 patients and 6 patients had 2 pregnancies. Eighteen of 25 patients (72.0%) had infertility problems; 17 patients conceived with IVF-embryo transfer and 1 patient with intrauterine insemination. The pregnancy rate among patients who wished to conceive was 36.2% (25/69). Among 31 pregnancies in 25 patients, 4 patients had first trimester miscarriage and 1 patient had second trimester miscarriage. Excluding the five patients who miscarried and the five ongoing pregnancies, all the 21 patients had deliveries by Cesarean section. Four patients had a preterm birth in the second trimester and 17 patients delivered in the third trimester. Of the 17 pregnancies that reached the third trimester, 2 (11.8%) were preterm births between 29 and 32 weeks, 11 (64.7%) were delivered between 32 and 37 weeks and 4 (23.5%) at ≥ 37 weeks of gestation. LIMITATIONS, REASONS FOR CAUTION: Because of the retrospective data collection, not all pregnancies may have been recorded. WIDER IMPLICATIONS OF THE FINDINGS: Prospective multicenter studies are needed to determine if the results shown in this retrospective cohort can be generalized to all patients with early-stage cervical cancer who wish to undergo the fertility-sparing RAT procedure.

Marked decline in beta cell function during pregnancy leads to the development of glucose intolerance in Japanese women.

The aim of this study is to investigate glucose metabolism longitudinally during pregnancy to explore mechanisms underlying gestational diabetes mellitus (GDM). We reviewed a total of 62 pregnant Japanese women who underwent a 75g oral glucose tolerance test (OGTT) twice during pregnancy (median: early, 13; late, 28 weeks' gestation) because of positive GDM screening. All showed normal OGTT results in early pregnancy. Based on late OGTT, 15 had GDM (late-onset GDM) and 47 normal glucose tolerance (NGT). In early pregnancy, there were no significant differences in insulin sensitivity (insulin sensitivity index derived from OGTT [IS(OGTT)] and homeostasis model assessment for insulin resistance [HOMA-IR]) and insulin secretion (a ratio of the total area-under-the-insulin-curve to the total area-under-the-glucose-curve [AUC(ins/glu)] and insulinogenic index [IGI]) between the NGT and late-onset GDM groups. In each group, insulin sensitivity significantly decreased from early to late pregnancy, most in the late-onset GDM group (each p < 0.05). The insulin secretion showed no significant changes with advancing pregnancy in both of the groups, although late-onset GDM showed significantly lower IGI compared with NGT in late OGTT (p < 0.05). When assessed beta cell function by OGTT-derived disposition index (i.e. Insulin Secretion-Sensitivity Index-2 and IGI/fasting insulin), the indices significantly decreased from early to late pregnancy in the both groups (each p < 0.05). Women with late-onset GDM showed significantly lower indices compared with NGT (each p < 0.05). The failure of beta cell to compensate for decreased insulin sensitivity could contribute to the development of the late-onset GDM.

Perinatal outcomes: intravenous patient-controlled fentanyl versus no analgesia in labor.

AIM: To investigate perinatal outcomes, the analgesic efficacy and maternal satisfaction in nulliparous women receiving fentanyl intravenous patient-controlled analgesia (i.v.-PCA). MATERIAL AND METHODS: A total of 1401 nulliparous women with a singleton pregnancy who received fentanyl i.v.-PCA (i.v.-PCA group, n = 290) or no analgesia (control group, n = 1111) in labor between 2005 and 2010 were reviewed. Fentanyl i.v.-PCA was implemented on maternal request during the first stage of labor over 35 weeks of gestation, and discontinued at full cervical dilatation. Perinatal outcomes were compared between the i.v.-PCA and the control groups. The numerical rating scale (NRS) levels during labor were also examined in the i.v.-PCA group. Additionally, parturients received fentanyl i.v.-PCA in 2010 (n = 73) were asked about overall satisfaction using a scale poor, moderate, good and excellent on postpartum day 0-3. RESULTS: Women receiving i.v.-PCA showed significantly longer labor and more need of oxytocin augmentation, compared with the control. Cesarean section was significantly less frequent in the i.v.-PCA group compared with the control (11.0% v.s. 24.1%, respectively), with the vacuum-assisted delivery rate comparable between groups. Neonatal outcomes (i.e. Apgar score <7 at 1 min or 5 min, umbilical artery pH <7.20) were comparable between groups, irrespective of mode of delivery. Significant reduction of NRS levels was noted until 3 h after induction of i.v.-PCA, compared to the baseline. Of the women who expressed their satisfaction, 72% (48/67) exhibited 'excellent' or 'good' for pain relief by i.v.-PCA. CONCLUSION: Fentanyl i.v.-PCA could be a useful approach for labor pain relief in nulliparas when regional blocks are unavailable.

Congenitally corrected transposition of the great arteries.

Congenitally corrected transposition of the great arteries (cTGA) is an uncommon cardiac malformation characterized by discordant atrioventricular and ventriculoarterial connections. Most cases of cTGA are associated with cardiac anomalies. As the ventricular outflow tract may appear to arise correctly from the right and left ventricles, cases of cTGA with a mild associated anomaly are rarely detected prenatally. Parallel vessels are evident in cTGA, but this sign is also present in complete TGA. We report a case of cTGA diagnosed in utero at 29 weeks' gestation. The fetus was diagnosed as TGA and referred to our hospital at 28 weeks' gestation. cTGA was found at 29 weeks' gestation in our hospital, and no additional cardiac anomalies were seen prenatally. After birth, patent ductus arteriosus with bidirectional flow was present. Careful examination of the four-chamber view suggested atrioventricular discordance. Identification of a parallel course of the great vessels, with the aorta anterior and to the left of the pulmonary trunk (l-transposition), may help accurate prenatal diagnosis of cTGA.

Pancreatic beta-cell function and fetal growth in gestational impaired glucose tolerance.

OBJECTIVE: To investigate the metabolic phenotype and pregnancy outcomes of gestational impaired glucose tolerance (IGT) defined by isolated hyperglycemia during an oral glucose tolerance test (OGTT). DESIGN: Retrospective cohort study. SETTING: University referral hospital. POPULATION: A total of 4,789 women were screened for gestational diabetes mellitus (GDM) between 1996 and 2008 with a glucose challenge test (GCT), followed by a 2-hour 75-g OGTT if the GCT result was abnormal; in addition, measurement of plasma insulin concentration during the OGTT was implemented from 2004. METHODS: The insulin sensitivity (IS(OGTT)) and beta-cell function (insulinogenic index/homeostasis model assessment for insulin resistance) were calculated for 283 women who underwent a diagnostic OGTT between 2004 and 2008. Perinatal complications were examined in 4,789 women who were screened for GDM between 1996 and 2008. MAIN OUTCOME MEASURES: Comparison of outcomes among women stratified by glucose tolerance status using the GCT and OGTT profiles. RESULTS: Insulin sensitivity and beta-cell function significantly decreased from normal OGTT to 2-hour IGT (single hyperglycemia at 2 hours) to 1-hour IGT (single hyperglycemia at 1 hour) to GDM, with significant differences between normal OGTT and 1-hour IGT or GDM. The occurrence of large-for-gestational age (LGA) neonates was significantly increased in women with GDM or 1-hour IGT (adjusted odds ratio: 2.15, 2.22; 95% confidence interval 1.23-3.75 and 1.04-4.35, respectively) compared to those with normal GCT or normal diagnostic OGTT results. CONCLUSIONS: Like GDM, isolated 1-hour hyperglycemia on the OGTT is associated with beta-cell dysfunction and an increased risk for LGA neonates.

Expression of ovary-specific acidic protein in steroidogenic tissues: a possible role in steroidogenesis.

Ovary-specific acidic protein (OSAP) is a novel molecule discovered from a genomic project designed to identify ovary-selective genes in mice. Whereas public databases suggest extraovarian expression of OSAP, its tissue distribution has not yet been well documented. Thus, the expression profile of mouse and human OSAP was determined by quantitative real-time RT-PCR using RNAs isolated from various tissues. The results demonstrate that the human and mouse OSAP expression profiles are similar; OSAP is prominently expressed in steroidogenic tissues with the highest level of expression observed in the adrenal gland. Placenta served as an exception and possessed minimal level of OSAP mRNA. Immunohistochemical studies show that mouse OSAP localizes almost exclusively to the steroid-producing cells of the ovary, adrenal gland, and testis. Consistent with predictions made by several subcellular localization algorithms, dual labeling studies in Y-1 mouse adrenocortical cells indicate OSAP resides in the mitochondria. Because of its abundant expression in steroidogenic cells and mitochondrial localization, a role for OSAP in steroidogenesis was determined. OSAP silencing by specific small interfering RNAs significantly inhibits 8-bromoadenosine-cAMP-induced progesterone production in Y-1 cells. Reduction in OSAP levels results in mitochondrial fragmentation and a decrease in the cellular content of mitochondrial DNA, indicative of decreased mitochondrial abundance. Lastly, 8-bromoadenosine-cAMP does not regulate OSAP protein expression in Y-1 cells as is the case for other steroidogenic components known to be induced by cAMP. Collectively these results suggest that OSAP is involved in steroidogenesis, potentially through its ability to maintain mitochondrial abundance and morphology.

Prenatal diagnosis of retroperitoneal teratoma: a case report and review of the literature.

We report a case of retroperitoneal teratoma diagnosed prenatally by serial sonographic examinations in the third trimester. A 29-year-old woman was referred for sonographic evaluation at 33 weeks' gestation because of a fetal intra-abdominal mass. Our initial sonographic image suggested a neuroblastoma. Repeat ultrasound images demonstrated an increase in size of the tumor, while the content of the tumor became predominantly solid with areas of calcification. Teratoma should be considered on detection of any cystic or mixed semisolid mass, especially when calcification is present. The fetus was prenatally diagnosed with retroperitoneal teratoma. After birth at 39 weeks, the tumor was removed and histological analysis revealed an immature retroperitoneal teratoma. Intensive monitoring of the changes in ultrasound images of the tumor should provide ground for a precise antenatal diagnosis.

Occipital scalp hemangioma: prenatal sonographic and magnetic resonance images.

Fetal scalp hemangioma in the occipital region is extremely rare and its accurate diagnosis is essential for perinatal management. We present a case of occipital scalp hemangioma diagnosed by prenatal sonography and magnetic resonance imaging (MRI). An echogenic mass measuring 29 mm x 23 mm x 30 mm was found in the occipital region by sonography at 20 weeks of gestation. Color-flow Doppler sonography depicted vascularity only at the periphery of the mass. The MRI results indicated that the extracranial mass exhibited a heterogeneous appearance of predominantly hyperintensity on T1- and hypointensity on T2-weighted images without evidence of fat signals, suggesting a soft tissue lesion containing blood products. Based on sonographic and MRI findings, the fetus was diagnosed to have occipital scalp hemangioma. Postmortem examination revealed cavernous hemangioma with hemorrhage. The MRI was a valuable adjunct to sonography for prenatal evaluation of an occipital lesion.

The periphery of the human fetal adrenal gland is a site of angiogenesis: zonal differential expression and regulation of angiogenic factors.

CONTEXT: Although the inner fetal zone (FZ) of the mid-gestation human fetal adrenal (HFA) produces dehydroepiandrosterone sulfate, the function of the outer definitive zone (DZ) remains less clear. We have proposed that the DZ phenotype is that of a pool of progenitor cells, many of which are mitotically active. Recently, we studied HFA expression of a family of vascular endothelial cell-specific angiogenic factors, the angiopoietins (Angs), and demonstrated that Ang2 was localized predominantly in the periphery of the gland. Ang1 stabilizes, whereas Ang2 destabilizes, vessels, increasing responsiveness to angiogenic stimuli such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF)-2. OBJECTIVE: Our objective was to test the hypothesis that the periphery of the HFA is a site of angiogenesis. DESIGN: Studies were conducted involving RNA, frozen sections, and primary cell cultures from midgestation HFAs. MAIN OUTCOME MEASURES: Immunofluorescence, laser capture microdissection, and real-time quantitative RT-PCR were used. RESULTS: Double immunostaining demonstrated that proliferating endothelial cells were limited to the DZ and DZ/FZ border. Ang2 mRNA was primarily expressed in the DZ, whereas Ang1 mRNA was primarily in the FZ. VEGF-A and FGF-2 mRNA levels were higher in the DZ. FGF-2 (10 ng/ml) induced Ang2 mRNA by 4-fold in both zones of cells (P < 0.01, at 24 h), but not Ang1 or VEGF-A mRNA. CONCLUSION: Data suggest that angiogenesis occurs at the periphery of the HFA. The DZ-predominant expression of Ang2 may be explained, in part, by the parallel pattern of FGF-2 expression.