Treatment of twin-reversed arterial perfusion sequence using high-intensity focused ultrasound.

We describe our experience of high-intensity focused ultrasound (HIFU) for fetal therapy in twin-reversed arterial perfusion (TRAP) sequence. Six pregnant women underwent HIFU therapy, five before 16 weeks and one at 26 weeks. Two types of HIFU system were used: the first-generation system, which comprised a biaxial transducer and continuous exposure pattern, and the second-generation system, which comprised a coaxial transducer and sequential exposure pattern. The first-generation apparatus was used in four cases and the second-generation apparatus was used in two. In three cases, occlusion of the blood vessels mediating flow to the acardiac twin was achieved by HIFU. Two cases experienced intrauterine fetal death despite vessel occlusion. The total survival rate of pump fetuses 2 years after HIFU was 67% and the efficiency rate (the proportion of cases with occlusion or reduced blood flow on ultrasound after HIFU) was 83%. After more than 2 years of follow-up, the surviving infants had no severe clinical complications and no postnatal developmental problems. There was no significant difference in survival rate compared with TRAP cases managed expectantly. Given that complete occlusion of the blood vessels was not achieved in half of the cases, we could not show that HIFU therapy is superior to other treatments. However, HIFU can reduce the cardiac load of the pump fetus and, as it does not require uterine puncture for fetal therapy, there were no fatal complications, such as bleeding, rupture of membranes or infection. Thus, HIFU therapy may represent a less-invasive treatment for TRAP sequence in early pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Coupling between the photo-excited cyclic π system and the 4f electronic system in a lanthanide single molecule magnet.

A new type of electronic interaction which couples two angular momenta, i.e. the angular momentum of a localized 4f system (J) and an orbital angular momentum generated in a cyclic π conjugated system by irradiation with a circularly-polarized light, has been identified in a lanthanide single molecule magnet.

Follow-up study of symptomatic submucous fibroids after hysteroscopic myomectomy.

PURPOSE OF INVESTIGATION: This study aimed to estimate the effectiveness of hysteroscopic myomectomy for symptomatic submucous uterine fibroids and to identify prognostic factors for persistent or recurrent symptoms. MATERIALS AND METHODS: A total of 237 patients who underwent hysteroscopic myomectomy were divided into three groups according to the classification of the European Society for Gynaecological Endoscopy: Type 0 (n=116), Type I (n=97), and Type II (n=24). Medical records and videotape records of all patients were retrospectively reviewed. RESULTS: Improvement of symptoms was achieved in 100% of Types 0 and I, and 66.7% of Type II. The five-year cumulative symptom-free rates after hysteroscopic myomectomy were 96.7% ± 1.9%, 87.8% 6.7%, and 44.5% ± 12.7% in Types 0, I, and II, respectively. The mean symptom-free periods were 46.2 ± 2.6, 47.7 ± 2.7, and 24.7 ± 6.3 months in Types 0, I, and II, respectively. Logistic regression analysis showed that co-existence of other myomas and Type II were independent prognostic factors for recurrence of symptoms. CONCLUSION: Type I fibroids are a good indication for hysteroscopic myomectomy. In Type II, some patients feel that their symptoms improve, but this curative effect could be temporary.

The relation between causes and onset time of polyhydramnios.

The aim of this analysis was to investigate the onset time and significance of maximum volume of polyhydraminios and whether the tter was associated with causes. This was a retrospective cohort study between 2012 and 2014. A total number of 68 singleton pregancies were analyzed. Gestational age at onset of polyhydramnios was 30.0 ± 2.8 (25-36) weeks in maternal factor, 30.0 ± 3.5 (25- 7) weeks in fetal factor, and 32.3 ± 2.0 (27-37) weeks in idiopathic factor. Median of maximum amniotic fluid index (AFI) was gnificantly late onset in idiopathic factor. Diabetes, gestational or pre-existing, was present in all of women (ten cases) in maternal facror. Higher AFI was found to be associated with an increased frequency of prenatally detected congenital anomalies. Abnormal fetal kary- type noted in 18/45 (40%) cases of polyhydramnios. Polyhydramnios diagnosed on ultrasound requires further maternal and fetal iagnostic tests.

Histologic chorioamnionitis prevalence in patients with premature rupture membranes.

This was a retrospective cohort study between 2002 and 2011. A total number of 150 singleton pregnancies with preterm premature rupture of membranes (PROM) (before 34 weeks) were analyzed. Histological chorioamnionitis (Blanc grade III) was significantly increased over three days from onset of premature rupture of membranes. The positive relationship was strengthened (odds ratios, 3.5; 95% confidence intervals, 1.5-5.2) over three days from onset of preterm PROM. PROM is a risk factor important for histological chorioamnionitis. To avoid neonatal infection, early termination is recommended in preterm PROM patients.

Retroperitoneal leiomyosarcoma: a case report.

Retroperitoneal leiomyosarcoma is a relatively rare and aggressive tumor. Because of its rarity, it is difficult to arrive at a definite diagnosis preoperatively and to design an effective strategy. Here the authors report a case of peritoneal leiomyosarcoma in which diagnosis was difficult because the clinical course resembled that of ovarian cancer. A 77-year-old woman diagnosed with ovarian cancer underwent laparotomy. The excised tumor contained a necrotic polypoid mass that histologically displayed the features of leiomyosarcoma. The patient received adjuvant chemotherapy with a combination of gemcitabine and docetaxel but died two months after surgery owing to the aggressive behavior of the tumor. Because the preoperative diagnosis in this case was ovarian cancer, arriving at a treatment strategy assuming peritoneal leiomyosarcoma was difficult. If complete surgical resection of tumor is not performed, as in the present case, the prognosis can be extremely poor.

Seminoma leading to detection of testicular feminization syndrome: a case report.

The authors here report a 54-year-old (gravida 0, para 0), who claimed to have had her menarche at age 13 and menopause at 52 years. Two months prior to presentation, the subject first noticed a hard but elastic fist-sized mass in the left inguinal region that gradually grew, causing pressure-related pain. Although the external genitalia appeared female, the vagina was short and blind-ending, and no uterus or ovaries were identified on transvaginal ultrasound. Chromosome banding results (G-band method) showed 46XY. Laparoscopy revealed no traces of a vestigial uterus or ovaries; thus, based on the appearance of the external genitalia, a diagnosis of testicular feminization syndrome was made. Pathological testing of the palpable mass led to a diagnosis of seminoma with Leydig cell hyperplasia. Thus, in this case, the development of a seminoma in an undescended testis led to the detection of testicular feminization syndrome.

Rupture risk factors of fallopian tubal pregnancy.

The present authors analyzed patients' backgrounds and pre-surgical findings to clarify the risk factors of rupture of fallopian tubal pregnancy. The surgical findings 113 cases were clearly diagnosed as fallopian tubal pregnancy with or without rupture. Twenty-six cases of fallopian tubal pregnancy were ruptured and 87 cases were not ruptured at the time of operation. The risk factors of fallopian tubal rupture were assessed by Chi-square for independence test and multiple regression analysis. Obesity (BMI over 26), prior birth history, social welfare entitlement, ultrasonography findings of fetal heart movement, and pre-surgical serum beta-hCG level more than 3,000 mIU/ml patient were significantly higher risk in fallopian tubal rupture. Fertility treatment patient were at significantly lower risk for fallopian tubal rupture. Higher beta-hCG levels, especially >3,000 mIU/ml is associated with increased risk of fallopian tubal rupture in ectopic pregnancy.

First successful case of non-invasive in-utero treatment of twin reversed arterial perfusion sequence by high-intensity focused ultrasound.

High-intensity focused ultrasound (HIFU) has excellent potential as a non-invasive therapeutic tool in various fields of medicine. We present a case of twin reversed arterial perfusion sequence, in which non-invasive blood flow occlusion in the acardiac fetus was successfully achieved by means of HIFU exposure from outside the maternal abdomen. HIFU was applied to blood vessels of the acardiac fetus at the point at which the umbilical cord entered the body in a series of four procedures at 3-day intervals starting at 13 weeks' gestation, and in a final procedure with higher power at 17 weeks. The HIFU intensity was set at approximately 2300 W/cm(2) for the initial series of procedures and at 4600 W/cm(2) for the final procedure, with exposure periods of 10 s. As color Doppler examination revealed absence of blood flow to the acardiac fetus after the second round of HIFU exposure, we concluded that complete occlusion of target vessels had been achieved. Delivery was by Cesarean section at 37 weeks' gestation. A male neonate (the pump fetus) was born weighing 1903 g with Apgar scores of 8 and 9 at 1 and 5 min, respectively. At the time of writing, the baby was healthy and growing normally, with the exception of congenital pseudarthrosis.

Effect of Zingiber zerumbet essential oils and zerumbone inhalation on body weight of Sprague Dawley rat.

Zingiber zerumbet contained the typically essential oils. The research aims to evaluate the effect Z. zerumbet essential oil and zerumbone inhlation on rats body weight, food consumption, parasympathetic nerve activity and brown adipose tissue temperature. The essential oils of Z. zerumbet was isolated from the rhizome of Z. zerumbet. The component in the oil and zerumbone structure was determined by gas chromatography-mass spectroscopy. The structure of zerumbone crystal was determined by nuclear magnetic resonance spectroscopy. The Sprague dawley male adult rats were divided into 4 groups namely Normal Diet (ND) group, High Fat Diet (HFD) group, HFD inhaled Z. zerumbet essential oils group and HFD inhaled zerumbone group. The results showed that inhalation of Z. zerumbet essential oils and zerumbone increased the food consumption as well as increased the body weight. The increasing body weight of rats which inhaled Z. zerumbet essential oils and zerumbone is by decreasing the sympathetic nerve activity. In conclusion, inhaling Z. zerumbet essential oils and zerumbone as the major component of the oils increased the weight gain.

High-intensity focused ultrasound treatment for twin reversed arterial perfusion sequence.

Twin reversed arterial perfusion (TRAP) sequence is a serious complication of monochorionic twin pregnancies, in which arterioarterial anastomoses allow blood flow from a 'pump' fetus to an acardiac fetus via reversed flow in the latter's umbilical artery. Several trial treatments for TRAP sequence have been reported, but all of these have been invasive. We present a case of TRAP sequence in which high-intensity focused ultrasound (HIFU) was applied to the umbilical artery of the anomalous twin at 26 weeks as a non-invasive fetal therapy. The HIFU intensity was set at approximately 2300 W/cm(2) with exposure periods of 10 s. Color Doppler ultrasound showed a decrease in blood supply to the anomalous twin, although complete occlusion of the targeted vessel was not achieved. Delivery was by Cesarean section at 29 weeks' gestation and the pump twin survived, without severe clinical complications at 6 months.

PP077. Effect of maternal antioxidant concentrations on expressions of angiogenesis-related genes in the villous trophoblasts from early pregnancy.

INTRODUCTION: The pathogenesis of preeclampsia is associated with oxidative stress of villous trophoblasts in early pregnancy. We have reported that antioxidant supplementations from 12weeks of gestation could prevent mild preeclampsia in pregnant women with oxidative stress. OBJECTIVES: To prove the effect of maternal antioxidant concentrations on expressions of angiogenesis-related genes in the villous trophoblasts from early pregnancy. METHODS: Villous tissue and blood samples were obtained from pregnant women who had artificial abortions between 6 and 11weeks of gestation. RNA was extracted from villous tissue, and gene expression levels of fms-like tyrosine kinase-1 (FLT-1), endoglin (ENG), and placental growth factor (PGF) in villous tissue were measured by reverse transcription polymerase chain reaction. Serum vitamin C and E concentrations were measured by enzyme-linked immunosorbent assay. This study was approved by the Ethics Committee of Showa University Hospital. RESULTS: Negative correlations between maternal serum vitamin C levels and gene expressions of ENG (r=-0.856, p=0.007) and FLT-1 (r=-0.898, p=0.002) in the villous trophoblasts were observed. There was no correlation of maternal serum vitamin E concentration with any other gene expression in the villous trophoblasts. CONCLUSION: It is suggested that maternal oxidative stress may increase the gene expressions of anti-angiogenic factors in villous trophoblasts of early gestation, which may lead to the pathogenesis of preeclampsia.

PP104. Pregnancy-induced hypertension is a strong risk factor for hypertension just 5 years after delivery: A double cohort study at the National Center for Child Health and Development and Showa University Hospital, Tokyo.

INTRODUCTION: Pregnancy-induced hypertension (PIH) is associated with increased risk for cardiovascular diseases later in life. OBJECTIVES: To assess the prevalence of subsequent hypertension and other life-style diseases five years after delivery in women who experienced pregnancy- induced hypertension. METHODS: A total of 1527 women who delivered singletons were registered at the National Center for Child Health and Development and Showa University Hospital Mother and child health center of integrated perinatal period between 2003 and 2005. After five years, these women were invited to participate in this study by mail, and 816 women completed the analysis. The women visited our hospital and underwent a medical examination. Women who were pregnant and nursing at the time when the physical examination was conducted were excluded from this survey. The outcomes assessed included the prevalences of hypertension, diabetes, and dyslipidemia. RESULTS: The number of PIH cases was 27 (3.3%: PIH group), whereas 787 women were used as controls subjects. The mean blood pressure five years after delivery was higher in the PIH group than in the control group (91.6±15.5mmHg vs 82.4±8.8mmHg, respectively; p<0.001), and the prevalence of hypertension five years after labor was 18.5% in the PIH group and 2.9% in the controls (odds ratio UOR Y=6.2; 95% confidence interval (CI)=2.2-17.5; p=0.003). Moreover, regarding high-normal blood pressure (>130/85mmHg), the prevalence was 33.4% in the PIH group and 6.1% in the control subjects (OR=7.2; 95% CI=3.1-16.3; p=0.003). No differences in the prevalences of subsequent diabetes or dyslipidemia were observed. CONCLUSION: Five years after the index pregnancy, women who experienced PIH exhibit an increased risk for subsequent hypertension. Therefore, the blood pressure of women with history of PIH should be regularly monitored after delivery.

Location of the placenta or the umbilical cord insertion site in the lowest uterine segment is associated with low maternal blood pressure.

OBJECTIVE: To evaluate whether placental abnormalities and umbilical cord insertion site affect the occurrence of pre-eclampsia and maternal blood pressure. DESIGN: Case-control study. SETTING: Showa University Hospital, Tokyo, Japan. POPULATION: A total of 5722 consecutive women who delivered singleton infants were included in the study. METHODS: The associations of placental abnormalities, the location of the placenta, the location of the cord insertion site, and maternal background with the occurrence of pre-eclampsia and maternal blood pressure at the term of pregnancy were analysed. MAIN OUTCOME MEASURE: Pre-eclampsia and maternal blood pressure at the term of pregnancy. RESULTS: Pre-eclampsia was observed in 236 women (4.1%). Pre-eclampsia was frequently observed in women with placental form abnormalities (odds ratio 3.0) and infarction of the placenta (odds ratio 5.3). Pre-eclampsia was observed in 0 and 4.1% of women with and without placenta praevia, respectively (P = 0.004), and in 0 and 2.5% of women with and without low cord insertion during the first trimester, respectively (P = 0.018). After adjustment for confounding variables, the multivariate regression analyses revealed reductions of 8.4 and 5.0 mmHg in systolic and diastolic blood pressure, respectively, in women with placenta praevia compared with women without placenta praevia, and reductions of 4.3 and 3.1 mmHg in systolic and diastolic blood pressure, respectively, in women with low cord insertion during the first trimester compared with women without low cord insertion. CONCLUSION: Not only placenta praevia but also low cord insertion are associated with low frequencies of pre-eclampsia and low maternal blood pressure.

Detection of umbilical venous constriction by Doppler flow measurement at midgestation.

OBJECTIVES: To investigate whether umbilical venous velocity and venous velocity pulsation are associated with umbilical vein diameter, umbilical ring diameter and umbilical cord coiling index at midgestation. METHODS: Two hundred and eighty pregnant women were enrolled in the study at between 18 and 24 weeks of gestation. The diameter of the umbilical cord and internal diameter of the umbilical vein in a free loop and at the ring, and the umbilical coiling index, were measured using ultrasonography. Umbilical venous velocities were measured by Doppler ultrasonography at the umbilical ring and a free loop of the cord. RESULTS: All variables were successfully measured in 92% of the patients. There were negative correlations between the diameters of the umbilical ring and of the umbilical vein at the ring and the venous velocity at the umbilical ring. The venous velocity at the umbilical ring was significantly higher and the umbilical ring diameter was significantly lower in fetuses with umbilical venous pulsation at the free loop. Significant correlations were observed between the venous velocity and amplitude of pulsation. Venous pulsations at the free loop were frequently observed in fetuses with a hypercoiled cord. CONCLUSION: High venous velocity and increased venous pulsation at the umbilical ring may be associated with umbilical cord constriction.

Predisposing factors for massive hemorrhage during Cesarean section in patients with placenta previa.

OBJECTIVES: To investigate whether maternal history and ultrasound findings can be predictors for massive hemorrhage during Cesarean section in patients with placenta previa and adherence of the placenta. METHODS: We reviewed 127 singleton pregnancies with placenta previa. Maternal history, antenatal ultrasound findings of the placenta, including location, presence of placental lacunae, lack of a clear zone, presence of sponge-like findings of the cervix and presence of a marginal sinus in cases of placenta previa were reviewed retrospectively, and their association with amount of bleeding during Cesarean section was analyzed. RESULTS: Logistic regression analysis revealed that advanced maternal age (odds ratio (OR), 5.4; 95% CI, 1.8-16.4), previous Cesarean section (OR, 20.4; 95% CI, 4.0-105.2) and sponge-like findings in the cervix (OR, 5.6; 95% CI, 1.8-17.0) were associated with massive bleeding (> 2500 mL). Placental adherence occurred in five cases and was more frequent in cases where the placenta was located at the site of the scar of a previous Cesarean section (OR, 123.1; 95% CI, 4.5-3395.2) and where there was lack of a clear zone (OR, 48.0; 95% CI, 3.8-604.7). CONCLUSIONS: Advanced maternal age, previous Cesarean section and presence of sponge-like findings in the cervix are risk factors for massive bleeding during Cesarean section in cases of placenta previa, regardless of whether placental adherence is present. Placental location on the scar of a previous Cesarean section and lack of a clear zone are risk factors for placental adherence. When these findings are identified preoperatively, management should be tailored accordingly.

Cost analysis of radiotherapy, carbon ion therapy, proton therapy and BNCT in Japan.

The purpose of this study was to estimate the financial costs to start BNCT as a clinical treatment in a hospital. To evaluate more accurate data on the precise costs of BNCT, we analyzed the costs of conventional radiotherapy, carbon ion and proton therapy and compare them to BNCT. An aggregate cost calculation of accelerator, buildings, equipments and staff requirements was performed.

A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disorder characterised by raised pulmonary artery pressures with pathological changes in small pulmonary arteries. Previous studies have shown that approximately 70% of familial PAH and also 11-40% of idiopathic PAH (IPAH) cases have mutations in the bone morphogenetic protein receptor type II (BMPR2) gene. In addition, mutations in the activin receptor-like kinase 1 (ALK1) gene have been reported in PAH patients. Since both the BMPR2 and ALK1 belonging to the transforming growth factor (TGF)-beta superfamily are known to predispose to PAH, mutations in other genes of the TGF-beta/BMP signalling pathways may also predispose to PAH. METHODS: We screened for mutations in ENDOGLIN(ENG), SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6 and SMAD8 genes, which are involved in the TGF-beta/BMP signallings, in 23 patients with IPAH who had no mutations in BMPR2 or ALK1. RESULTS: A nonsense mutation in SMAD8 designated c.606 C>A, p.C202X was identified in one patient. The father of this patient was also identified as having the same mutation. Functional analysis showed the truncated form of the SMAD8 C202X protein was not phosphorylated by constitutively active ALK3 and ALK1. The SMAD8 mutant was also unable to interact with SMAD4. The response to BMP was analysed using promoter-reporter activities with SMAD4 and/or ca-ALK3. The transcriptional activation of the SMAD8 mutant was inefficient compared with the SMAD8 wild type. CONCLUSION: We describe the first mutation in SMAD8 in a patient with IPAH. Our findings suggest the involvement of SMAD8 in the pathogenesis of PAH.

Application of high-intensity focused ultrasound for umbilical artery occlusion in a rabbit model.

OBJECTIVES: To investigate the application of high-intensity focused ultrasound (HIFU) for fetal umbilical artery blood flow occlusion in a rabbit model. METHODS: A prototype HIFU transducer in combination with an imaging probe with Doppler capability was constructed. Using this transducer, HIFU was applied at 1.4, 2.75 or 5.5 kW/cm(2) through the maternal abdominal skin to the fetal intra-abdominal umbilical arteries of four time-mated Japanese White rabbits (11 fetuses) on gestational day 25. Courses of 5-s HIFU exposure were performed until cessation of umbilical blood flow and cardiac arrest were confirmed by Doppler ultrasonography. Fetal necropsy was performed and exposed lesions were assessed by microscopic histological analysis. RESULTS: The mean diameter of the fetal umbilical artery was 0.6 +/- 0.2 mm and the mean peak systolic velocity of arterial blood flow was 44.7 +/- 18.5 cm/s. When HIFU was applied at 5.5 kW/cm(2), blood flow was completely occluded within 15 courses. HIFU exposure brought about vacuolar degeneration and destruction of elastic fibers in the tunica media of the artery. CONCLUSIONS: HIFU can be used to occlude umbilical artery blood flow in fetal rabbits.

Cord insertion into the lower third of the uterus in the first trimester is associated with placental and umbilical cord abnormalities.

OBJECTIVES: To assess the feasibility of detecting the cord insertion site during the late first trimester, and to investigate the possible association between perinatal complications and a cord insertion in the lower third of the uterus in the first trimester. METHODS: This was a prospective cohort study in which the positional relationship between the uterus and the cord insertion site was examined using gray-scale transvaginal sonography at 9-11 weeks of gestation. The distance between the internal os and the fundus was divided equally into three parts. Cord insertions located in the upper or middle thirds were defined as normal (controls), and those located in the lower third were defined as cases, regardless of their relationship to the chorion villosum. Third-trimester sonography and pathological examination of the placenta and cord at delivery were performed to check for placental/cord abnormalities. The univariate association between the location of the cord insertion in the first trimester and placental and umbilical cord abnormalities and perinatal complications was assessed. RESULTS: The cord insertion site was identified in 318/340 (93.5%) cases at 9-11 weeks of gestation and it was in the lower third of the uterus in 35 (11.0%) cases. Of these 35, the cord insertion was found at delivery to be low in nine cases (26%) and the placenta was low-lying at delivery in eight (23%). None of the 283 cases with a normal cord insertion in the first trimester was found to have a low-lying placenta at delivery (P < 0.0001). Ten (29%) of the cases with a low cord insertion and four (1.4%) with a normal cord insertion in the first trimester had a velamentous or marginal cord insertion at delivery (P < 0.0001). At delivery, five (14%) of the low cord insertion cases and four (1.4%) of the normal cord insertion cases (P < 0.0001) had some form of placental malformation, including accessory placenta and infarction of the placenta. An emergency Cesarean section was performed in four (11%) and six (2.1%) of the low and normal cord insertion cases, respectively (P = 0.003). CONCLUSION: Developmental abnormalities of the placenta and umbilical cord occur frequently in cases in which the cord insertion is in the lower third of the uterus in the first trimester. We suggest that screening for the cord insertion site at 9-11 weeks of gestation may have clinical significance for predicting abnormalities of the cord and the placenta at delivery.