Prevalence of common aneuploidy in twin pregnancies.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Risk factors of retained products of conception after miscarriage or termination with gemeprost in the second trimester of pregnancy: a retrospective case-controlled study in Japanese population.

Retained products of conception (RPOC) is a complication that occurs in the second trimester of pregnancy. We enrolled 98 women who had a miscarriage or termination with gemeprost in the second trimester of pregnancy. Eighteen cases (18.4%) were RPOC-positive. The gestational week at miscarriage or termination was earlier in the RPOC-positive group than those in the RPOC-negative group (p = .003). The period of the third stage of labour was longer in the RPOC-positive group than in RPOC-negative group (p = .040). The proportion of placental forceps use was higher in the RPOC-positive group than in RPOC-negative group (p = .003). Multivariate logistic regression analysis showed that gestational week (OR: 3.53; p = .04) and use of placental forceps at delivery (OR: 2.21; p = .012) were independent risk factors for RPOC. Earlier gestational weeks at miscarriage or termination and use of placental forceps at delivery were predictive factors for RPOC after second trimester miscarriage or termination with gemeprost.Impact StatementWhat is already known on this subject? There have been some reports on risk factors of RPOC. A previous report showed that the termination of pregnancy with misoprostol at earlier periods was associated with an increased risk of RPOC.What the results of this study add? There have been few studies on the risk factors of RPOC after miscarriage or termination with gemeprost. In this study, we evaluated the risk factors of RPOC after miscarriage or termination of pregnancy with gemeprost in the second trimester. We found that an earlier gestational age (between 12 and 17 weeks) at delivery and using placental forceps to remove placenta were significant risk factors of RPOC after miscarriage or termination of pregnancy with gemeprost in the second trimester.What the implications are of these findings for clinical practice and/or further research? An earlier gestational age and using forceps to remove placenta may be significant risk factors for RPOC. The accurate evaluation and treatment for RPOC is important for maternal life-saving efforts and subsequent pregnancies. Further research is needed to draft a standardised protocol for RPOC.

MYRF haploinsufficiency causes 46,XY and 46,XX disorders of sex development: bioinformatics consideration.

Disorders of sex development (DSDs) are defined as congenital conditions in which chromosomal, gonadal or anatomical sex is atypical. In many DSD cases, genetic causes remain to be elucidated. Here, we performed a case-control exome sequencing study comparing gene-based burdens of rare damaging variants between 26 DSD cases and 2625 controls. We found exome-wide significant enrichment of rare heterozygous truncating variants in the MYRF gene encoding myelin regulatory factor, a transcription factor essential for oligodendrocyte development. All three variants occurred de novo. We identified an additional 46,XY DSD case of a de novo damaging missense variant in an independent cohort. The clinical symptoms included hypoplasia of Müllerian derivatives and ovaries in 46,XX DSD patients, defective development of Sertoli and Leydig cells in 46,XY DSD patients and congenital diaphragmatic hernia in one 46,XY DSD patient. As all of these cells and tissues are or partly consist of coelomic epithelium (CE)-derived cells (CEDC) and CEDC developed from CE via proliferaiton and migration, MYRF might be related to these processes. Consistent with this hypothesis, single-cell RNA sequencing of foetal gonads revealed high expression of MYRF in CE and CEDC. Reanalysis of public chromatin immunoprecipitation sequencing data for rat Myrf showed that genes regulating proliferation and migration were enriched among putative target genes of Myrf. These results suggested that MYRF is a novel causative gene of 46,XY and 46,XX DSD and MYRF is a transcription factor regulating CD and/or CEDC proliferation and migration, which is essential for development of multiple organs.

Wakayama Medical University Hospital perinatal helicopter ambulance service: 14 year review.

BACKGROUND: In 2003, a perinatal helicopter air ambulance service was introduced for remote areas of Wakayama and Mie prefectures, Japan, but its long-term impact on perinatal medicine has not yet been analyzed. METHODS: A retrospective observational study was conducted on helicopter air ambulance cases recorded between January 2003 and December 2016 at Wakayama Medical University Hospital (WMUH). RESULTS: During that period, 61 pregnant mothers were transferred by helicopter air ambulance to WMUH. Between 2003 and 2009, the mean period from transfer to birth was 0.6 weeks, whereas between 2008 and 2016, this increased to 1.6 weeks, and the survival rate of infants born after transfer did not differ significantly (84.2%, 32/38 versus 82.1%, 23/28). Seventy-three neonates were transferred. The number transferred between 2003 and 2009 was 46, whereas this decreased to 27 between 2010 and 2016. The neonatal mortality rate in south Wakayama plus south Mie gradually decreased. The reasons for the longer period from transfer to birth, and the decrease in the rate of very low-birthweight infants after transfer may be due to development in the management of threatened premature labor, and the earlier transfer of such cases by regional obstetricians. The reasons for the decline in neonatal transfer may have included the development of fetal diagnostic techniques and improved efficiency of neonatal ground-transport in the South Wakayama region. CONCLUSION: The helicopter air ambulance is an important form of medical transportation in the south Kii peninsula.

Perinatal outcome of vaginal delivery with epidural analgesia initiated at the early or late phase of labor period: A retrospective cohort study in the Japanese population.

AIM: We compared the perinatal outcomes of vaginal delivery with epidural analgesia initiated at the early versus late phase in a Japanese population. METHODS: Women enrolled in this retrospective cohort study received intrapartum analgesia via combined spinal epidural analgesia after labor onset between May 2010 and August 2015. We compared the perinatal outcomes between two different timings of epidural analgesia: at the early phase (≤3 cm cervical dilatation) and the late phase (≥4 cm) or at the new definition-based early phase (≤5 cm) and late phase (≥6 cm). RESULTS: One hundred twenty-eight singleton pregnant women were eligible. In nulliparous women, there was no marked difference in perinatal outcomes between the early and late phase except for in the first-stage labor period (13.7 h vs 10.1 h, P = 0.016). In multiparous women, there was no marked difference in perinatal outcomes between the early and late phase except for a higher proportion of Apgar score ≤7 at 1 min in the early phase (20.0% vs 0.0%, P = 0.033). In nulliparous women, the first-stage labor period in the new early phase was significantly longer than in the new late phase (13.3 h vs 6.9 h, P = 0.035). Other variables for nulliparous women and all for multiparous women were not different between the new early and late phases. CONCLUSION: Most perinatal outcomes between the early and late phases of initiated epidural analgesia were not markedly different in our Japanese population, even when using a new definition of labor phase.

Placental mesenchymal dysplasia with severe fetal growth restriction in one placenta of a dichorionic diamniotic twin pregnancy.

We report a rare case of placental mesenchymal dysplasia (PMD) with fetal growth restriction (FGR) in one placenta of a dichorionic diamniotic (DD) twin pregnancy. A 24-year-old woman was referred to our hospital at 24 weeks' gestation due to FGR and ipsilateral placental abnormality in DD twins. Ultrasound and magnetic resonance imaging showed one placenta of the FGR fetus was bulky and had multiple cysts, while the other fetus placenta appeared normal. Cesarean section was performed at 32 weeks' gestation; the first and second neonates weighted 1799 and 1215 g, respectively. Macroscopically, chorionic vessels on the placental surface of the second neonate were prominently enlarged. Pathological findings demonstrated swelling stem villi with enlarged vessels and increased interstitial cells without trophoblast proliferation. Immunostaining for p57kip2 was negative in interstitial cells and cytotrophoblasts of the swelling stem villi. This suggested that PMD occurred in one placenta of the DD twin, leading to early-onset FGR.

Levels of serum-circulating angiogenic factors within 1 week prior to delivery are closely related to conditions of pregnant women with pre-eclampsia, gestational hypertension, and/or fetal growth restriction.

AIM: We aimed to investigate maternal serum angiogenic marker profiles within 1 week prior to delivery in cases of gestational hypertension (GH), pre-eclampsia (PE), and/or fetal growth restriction (FGR) with different clinical conditions. METHODS: We enrolled 165 women with singleton pregnancy. The participants were classified based on three characteristics: (i) proteinuria (GH and PE); (ii) FGR (PE with FGR [PE + FGR], PE alone, and FGR alone); and (iii) onset (early onset PE [EO PE] and late-onset PE [LO PE]). All sera were obtained within 1 week prior to delivery, and soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), and placental growth factor (PlGF) were measured with enzyme-linked immunosorbent assay. RESULTS: (i) In PE, a significantly increased sFlt-1, sEng, and sFlt-1 to PlGF ratio (sFlt-1/PlGF) and significantly decreased PlGF were observed compared with GH and Term control, whereas in GH, only sFlt-1/PlGF was significantly higher than Term control. (ii) In PE + FGR, similar changes were more markedly shown compared with PE alone. The FGR alone group exhibited similar tendencies as PE, although significant differences were found in PlGF and sEng levels. (iii) In EO PE, significant changes were observed in all factors compared with LO PE or Term control, while no significant change in PlGF levels was observed between LO PE and Term control. CONCLUSION: We demonstrated that the levels of circulating angiogenic factors just before delivery are correlated with the severity of hypertensive disorders of pregnancy and FGR. Profiling these specific markers may contribute to better understanding of the clinical conditions in individual patients and their pathogenesis.

Clinicopathologic Factors of Cervical Adenocarcinoma Stages IB to IIB.

OBJECTIVE: The aim of this study was to clarify the clinicopathologic factors of stages IB to IIB cervical adenocarcinoma. METHODS: Several clinicopathologic factors were compared between 35 patients who underwent radical hysterectomy and pelvic lymphadenectomy due to cervical adenocarcinoma stages IB to IIB and 77 patients with squamous cell carcinoma (SCC). RESULTS: In patients with adenocarcinoma, univariate analysis demonstrated that International Federation of Gynecology and Obstetrics stage, tumor size, and lymphovascular space invasion were significantly associated with progression-free survival (PFS), whereas FIGO stage, lymphovascular space invasion, and lymph node metastasis were significantly associated with overall survival (OS). However, multivariate analysis revealed that FIGO stage was the only significant factor for PFS in patients with adenocarcinoma. In patients with SCC, univariate analysis demonstrated that FIGO stage and lymph node metastasis were significantly associated with PFS, whereas FIGO stage, lymphovascular space invasion, and lymph node metastasis were significantly associated with OS. Multivariate analysis revealed that lymph node metastasis was the only significant factor for PFS and OS in patients with SCC. In 26 patients who were positive for high-risk human papillomavirus (HPV), including both adenocarcinoma and SCC patients, univariate and multivariate analyses revealed that HPV18 was significantly associated with poorer PFS compared with non-HPV18. There was a significant difference in distribution of HPV genotype between adenocarcinoma and SCC. CONCLUSIONS: Careful treatment may be necessary for the patients with lymphovascular space invasion in early-stage cervical adenocarcinoma. The presence of HPV18 may have an influence on the prognosis of early-stage cervical carcinoma.

Vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving chemotherapy and conservative surgery.

Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake (SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months.

Acute fatty liver of pregnancy associated with fetal mitochondrial trifunctional protein deficiency.

Acute fatty liver of pregnancy (AFLP) is a devastating disorder of the maternal liver in the third trimester. Recent studies have demonstrated an association between AFLP and fetal fatty acid oxidation disorders. Here, we report a case of AFLP caused by fetal mitochondrial trifunctional protein (TFP) deficiency. A 21-year-old parous woman presented with nausea, genital bleeding and abdominal pain at 33 weeks of gestation. Laboratory data revealed hepatic failure and disseminated intravascular coagulopathy. The patient underwent emergency cesarean section and was diagnosed with AFLP from the clinical characteristics. She was successfully treated with frequent plasma exchange. The newborn presented severe heart failure and died on the 39th day after birth. Tandem mass spectrometry indicated long-chain fatty acid oxidation disorder. Gene analysis demonstrated homozygous mutation in exon 13 of HADHB, the gene responsible for mitochondrial TFP deficiency. The parents carried a heterozygous mutation at the same location in HADHB.

Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that has immunoregulatory functions. Our prior study showed that tumoral IDO overexpression is involved in disease progression and impaired patient survival in human ovarian cancer, although its mechanism remains unclear. The purpose of the present study is to clarify the role of IDO during the process of peritoneal dissemination of ovarian cancer. Indoleamine 2,3-dioxygenase cDNA was transfected into the murine ovarian carcinoma cell line OV2944-HM-1, establishing stable clones of IDO-overexpressing cells (HM-1-IDO). Then HM-1-IDO or control vector-transfected cells (HM-1-mock) were i.p. transplanted into syngeneic immunocompetent mice. The HM-1-IDO-transplanted mice showed significantly shortened survival compared with HM-1-mock-transplanted (control) mice. On days 11 and 14 following transplantation, the tumor weight of peritoneal dissemination and ascites volume were significantly increased in HM-1-IDO-transplanted mice compared with those of control mice. This tumor-progressive effect was coincident with significantly reduced numbers of CD8(+) T cells and natural killer cells within tumors as well as increased levels of transforming growth factor-ß and interleukin-10 in ascites. Finally, treatment with the IDO inhibitor 1-methyl-tryptophan significantly suppressed tumor dissemination and ascites with reduced transforming growth factor-ß secretion. These findings showed that tumor-derived IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating effector T cell and natural killer cell recruitment and reciprocal enhancement of immunosuppressive cytokines in ascites, creating an immunotolerogenic environment within the peritoneal cavity. Therefore, IDO may be a promising molecular target for the therapeutic strategy of ovarian cancer.

Diagnostic value of preoperative SUVmax on FDG-PET/CT for the detection of ovarian cancer.

OBJECTIVE: The objective of this study was to investigate the preoperative diagnostic value of F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) in patients with ovarian cancer. METHODS: One hundred sixty patients suspected of having malignant ovarian tumors were included in this study. All patients underwent FDG-PET/CT scans before operation, and the maximum standardized uptake value (SUVmax) of the primary tumor was measured. We evaluated the diagnostic accuracy of SUVmax for detecting malignancy and its relationship with histological findings. RESULTS: Postoperative pathological diagnoses showed that 67 were malignant, 14 were borderline malignant, and 79 were benign tumors. With the use of a cutoff SUVmax of 2.9 obtained from the receiver operating characteristic curve analysis, the sensitivity, specificity, positive predictive value, and negative predictive value for detecting malignancy were 80.6%, 94.6%, 91.5%, and 87.1%, respectively. Positive FDG accumulation (SUVmax ≥ 2.9) was shown in 89.5% of serous adenocarcinoma and in 92.3% of endometrioid adenocarcinoma. In contrast, lower frequencies of positive FDG accumulation were shown in clear cell adenocarcinoma (54.5%), mucinous adenocarcinoma (66.7%), and metastatic carcinoma (66.7%), and the median SUVmax of these 3 histological types were significantly lower than those of serous and endometrioid types. In addition, a positive FDG accumulation was shown in all patients with malignant transformation of mature cystic teratoma. Finally, of the 14 borderline malignant tumors, only 2 (14.3%) showed positive FDG accumulation. CONCLUSIONS: The SUVmax on FDG-PET/CT is useful for differentiating ovarian cancer from borderline or benign tumor with a high specificity and positive predictive value. However, our data also demonstrated a lower FDG uptake value in clear cell or mucinous histological finding, suggesting that SUVmax may vary depending on the tumor histological subtype.

Ovarian steroid cell tumor, not otherwise specified, producing testosterone.

Steroid cell tumor, not otherwise specified, is a rare type of ovarian sex cord-stromal tumor with malignant potential. Some of these tumors produce testosterone. We describe a case of steroid cell tumor of the ovary associated with virilization. A 23-year-old nulliparous woman was found to have an ovarian tumor when she visited her primary doctor for virilization and oligomenorrhea. Magnetic resonance imaging revealed a solid left ovarian tumor 40 mm in size. Her laboratory data revealed elevated testosterone with normal levels of gonadotropins, estradiol, dehydroepiandrosterone sulfate and cortisol. She underwent left adnexectomy. On histopathologic and immunohistochemical analyses, the tumor was diagnosed as steroid cell tumor, not otherwise specified, without malignant behavior. After removal of the tumor, serum testosterone level decreased, and there have been no signs of recurrence.

Adverse perinatal and neonatal outcomes in patients with chronic abruption-oligohydramnios sequence.

AIM: Chronic abruption-oligohydramnios sequence (CAOS) is a clinical condition with lasting vaginal bleeding and oligohydramnios because of chronic placental abruption, which seems to cause preterm labor and neonatal chronic lung disease (CLD). This prompted us to explore the correlation between perinatal/neonatal outcomes and CAOS. METHODS: Patients with suspected risk of abortion with recurrent vaginal bleeding were divided into CAOS and non-CAOS groups, and we compared the perinatal/neonatal outcomes between these two groups. To examine the impact of chorioamnionitis (CAM) on the prognosis of CAOS, we also compared outcomes between the CAOS group and gestational-age-matched preterm labor due to CAM (CAM group). RESULTS: In the CAOS and non-CAOS groups, initial vaginal bleeding was seen at the first trimester. However, its duration was significantly longer in the CAOS group. Additionally, neonatal birthweight was lower, and small-for-gestational-age (SGA) incidence was higher in the CAOS group. CLD was observed in most infants from CAOS patients. In the comparison between CAOS and CAM groups, birthweight was lower and SGA incidence was higher in the CAOS group. Moreover, CLD incidence and neonatal mortality were significantly higher, despite the lower incidence of severe CAM in the CAOS group. Finally, multivariate analysis demonstrated that duration of bleeding was a significant predictive factor for CAOS. CONCLUSIONS: Our observations demonstrated that patients with CAOS were a high-risk group for poor perinatal/neonatal outcomes. Moreover, episodes of recurrent and prolonged uterine bleeding were predictive factors for CAOS. During the first trimester, prolonged bleeding is an important sign as one symptom of CAOS.

HBOC syndrome with an uncharacterized variant in the BRCA1 gene in a patient diagnosed with endometrial cancer after surgery for bilateral breast cancer: A case report.

The association between endometrial cancer and the BRCA1 and BRCA2 genes is not fully understood, and the risk elevation of endometrial cancer in patients with hereditary breast and ovarian cancer (HBOC) is not understood. The present report examines a rare case of HBOC syndrome and an uncharacterized variant of the BRCA1 gene in a patient diagnosed with endometrial cancer. A 46-year-old woman, gravida 1 para 1, was referred to Wakayama Medical University Hospital (Wakayama, Japan) because positron emission tomography/computed tomography (PET/CT) showed a high FDG uptake in the corpus uteri and the left ovary. PET/CT was performed just after mastectomy for left-sided breast cancer (triple negative). The patient had previously undergone partial mastectomy for right-sided breast cancer (triple negative) and was treated with radiation therapy to the right residual breast when she was 39 years old. Laparoscopic hysterectomy and bilateral adnexectomy were performed, and the histological diagnosis was endometrioid carcinoma, grade 1. Her germline BRCA status was tested by blood examination and the result was 'NM_007294.4(BRCA1):c.49G>C (p.Ala17Pro)'. The variant was evaluated as 'likely pathogenic'. The patient was diagnosed with HBOC syndrome and endometrial cancer, pT1ANxM0. The patient had no recurrence of breast or endometrial cancer 16 months after gynecologic surgery.

Changes in maternal and child health outcomes after introduction of a helicopter into perinatal transportation in Japan.

To examine the effect of perinatal helicopter transportation on maternal and child health. Helicopter transportation for the sparsely populated southern areas of Wakayama and Mie prefectures was introduced in June 2003. Maternal and child health statistics for 2000-2002 and 2004-2006 were compared between the south and north regions of the prefectures. There were 9 maternal transports from south Wakayama, 2 from north Wakayama, and 5 from south Mie in 2004-2006; and 13 neonatal transports from south Wakayama and 7 from north Wakayama during the same period. Decreases in neonatal and perinatal mortalities in 2004-2006 compared to 2000-2002 were greater in south Wakayama than in north Wakayama (-0.31 vs. -0.28, and -0.57 vs. -0.18, respectively); and greater in south Mie than in north Mie (-0.90 vs. -0.49, and -2.49 vs. -1.48, respectively). The changes in the number of maternal deaths between 2000-2002 and 2004-2006 were 0 in south Wakayama, 1 in north Wakayama, -2 in south Mie, and -1 in north Mie, with the greatest change occurring in south Mie. Use of a helicopter for perinatal transportation can possibly improve maternal and child health in sparsely populated areas far away from urban areas.

Low-grade endometrial stromal sarcoma in a young woman diagnosed after resection of endometrial polyp-like lesions: A case report.

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare tumor that mostly occurs in perimenopausal women. Treatment with total hysterectomy and bilateral salpingo-oophorectomy is recommended, although fertility preservation or ovarian preservation may be considered in younger patients. The present study reports a case of LG-ESS in a young woman diagnosed after resection of endometrial polyp-like lesions. A 26-year-old nulligravid woman was referred to our hospital after being diagnosed with endometrial polyps. Hysteroscopic endometrial polypectomy was performed twice, and LG-ESS was suspected on postoperative pathological examination. Magnetic resonance imaging revealed a tumor 5-cm in diameter on the right side of the uterus. In light of the young age of the patient, tumorectomy was first performed, and postoperative pathological diagnosis was LG-ESS with the positive resection margin. After thorough discussion with the patient about fertility preservation and recurrence risk, a total abdominal hysterectomy and ovarian preservation was performed. Medroxyprogesterone therapy was performed postoperatively and no recurrence was observed for 2 years.

Malignant melanoma treated with pembrolizumab during pregnancy: A case report and review of the literature.

There have been very few reports on the use of immune checkpoint inhibitors for malignant tumors during pregnancy. Herein, the current study reports a case of a patient diagnosed with advanced malignant melanoma who was treated with pembrolizumab during pregnancy. A 40-year-old primigravida underwent noninvasive prenatal testing at 10 weeks of gestation, and the result was inconclusive, suggesting the possibility of maternal malignancy. A biopsy of the gluteal mass led to a diagnosis of malignant melanoma, and computed tomography revealed extensive metastases in her lungs and lymph nodes. She had a strong desire to proceed with pregnancy. In consideration of fetal growth and maturation, monotherapy was administered with pembrolizumab from 21 weeks of gestation, aiming for 28 weeks of gestation. The fetus grew well without maternal complications. At 28 weeks of pregnancy, the patient gave birth to a healthy boy by cesarean section. There was no evidence of metastasis in the placenta. The patient received nivolumab-ipilimumab combination therapy from postpartum day 13, followed by nivolumab monotherapy, and has been alive with controlled disease for 20 months.

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

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

Short term outcomes of helical tomotherapy during concurrent chemoradiotherapy for advanced cervical cancer.

The aim of the present study was to clarify the feasibility and efficacy of helical tomotherapy during concurrent chemoradiotherapy for treating cervical cancer. The medical records of 13 patients who underwent oncurrent chemoradiotherapy using helical tomotherapy for cervical cancer at Wakayama Medical University Hospital between 2013 and 2015 were retrospectively reviewed. A total of 15 patients who underwent oncurrent chemoradiotherapy using conventional radiotherapy (CRT) between 2008 and 2013 at our institution were also examined for comparison. The median age of patients treated with helical tomotherapy was 60 (range, 35-71), and the median age of patients treated with CRT was 57 (range, 43-77). The median follow-up period was 27 months (range, 3-46) in the tomotherapy group and 35 months (range, 7-88) in the CRT group. The frequency of G3/4 thrombocytopenia in the tomotherapy group was significantly higher than that in the CRT group (P=0.049). However, the platelet count spontaneously recovered without transfusion. There were no significant differences between the groups in terms of frequency of G3/4 neutropenia, diarrhea or late intestine injury. The rate of complete response in the tomotherapy group and the CRT group was 84.6 and 73.3%, respectively, and there was no significant difference in the response rate between the groups. There were no significant differences in the progression-free survival or progression-free rate in the irradiation field between the groups. Adverse events from concurrent chemoradiotherapy using helical tomotherapy were acceptable and clinically controllable. The present results suggest that helical tomotherapy is efficient during concurrent chemoradiotherapy for treatment of advanced cervical cancer.