Quality of care measurement for patients with ovarian cancer in Japan.

AIM: Quality of care is important to reduce disease progression, and improve both survival and quality of life. The Japan Society of Gynecologic Oncology has published treatment guidelines to promote standardized high-quality care for ovarian cancer in Japan. We developed quality indicators based on the guideline recommendations and used them on large datasets of health service use to examine the quality of ovarian cancer care. METHODS: A panel of experts developed the indicators using a modified Delphi method. Adherence to each indicator was evaluated using data from a hospital-based cancer registry of patients diagnosed in 2018. All patients receiving first-line treatment at participating facilities were included. The adherence rates were returned to participating hospitals, and reasons for nonadherence were collected. A total of 580 hospitals participated, and the study examined the care received by 6611 patients with ovarian cancer and 1879 with borderline tumors using 11 measurable quality indicators. RESULTS: The adherence rate ranged from 22.6% for "Estrogen replacement within 6 months of operation" to 93.5% for "Bleomycin, etoposide, and cisplatin for germ cell tumor more than Stage II." Of 580 hospitals, 184 submitted the reasons for nonadherence. CONCLUSIONS: The quality of ovarian cancer care should be continuously assessed to encourage the use of best practices. These indicators may be a useful tool for this purpose.

Sentinel node navigation surgery in cervical cancer: a systematic review and metaanalysis.

Sentinel node navigation surgery (SNNS) is used in clinical practice for the treatment of cervical cancer. This study aimed to elucidate the appropriate sentinel lymph node (SLN) mapping method and assess the safety and benefits of SNNS. We searched the PubMed, Ichushi, and Cochrane Library databases for randomized controlled trials (RCT) and studies on SLN in cervical cancer from January 2012 to December 2020. Two authors independently assessed study quality and extracted data. We quantitatively analyzed the detection rate, sensitivity/specificity, and complications and reviewed information, including the survival data of SLN biopsy (SLNB) without pelvic lymphadenectomy (PLND). The detection rate of SLN mapping in the unilateral pelvis was median 95.7% and 100% and in the bilateral pelvis was median 80.4% and 90% for technetium-99 m (Tc) with/without blue dye (Tc w/wo BD) and indocyanine green (ICG) alone, respectively. The sensitivity and specificity of each tracer were high; the area under the curve of each tracer was 0.988 (Tc w/wo BD), 0.931 (BD w/wo Tc), 0.966 (ICG), and 0.977 (carbon nanoparticle). Morbidities including lymphedema, neurological symptoms and blood loss were associated with PLND. One RCT and five studies all showed SNNS without systematic PLND does not impair recurrence or survival in early-stage cervical cancer with a tumor size ≤ 2-4 cm. Both Tc w/wo BD and ICG are appropriate SLN tracers. SNNS can reduce the morbidities associated with PLND without affecting disease progression in early-stage cervical cancer.

Clinicopathological characteristics and prognostic factors of ovarian granulosa cell tumors: A JSGO-JSOG joint study.

OBJECTIVES: The aim of this study was to elucidate the clinicopathological features of ovarian granulosa cell tumors (GCTs) and to identify the prognostic factors. METHODS: The Japanese Society of Gynecologic Oncology (JSGO) conducted an observational retrospective cohort study of women with GCTs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology (JSOG) between 2002 and 2015. Clinicopathological features, including lymph node metastasis, were evaluated. In addition, we performed a prognostic analysis of patients between 2002 and 2011 for whom survival data were available. Kaplan-Meier and multivariate Cox proportional hazards analyses were performed. RESULTS: We identified 1426 patients with GCTs. Of the 222 patients who underwent lymph node dissection, 10 (4.5%) had lymph node metastasis. The incidence of lymph node metastasis in patients with pT1, pT2, and pT3 was 2.1%, 13.3%, and 26.7%, respectively (p < 0.001). Prognostic analysis was performed on 674 patients. In the multivariate Cox regression analysis, residual disease after initial surgery (hazard ratio (HR) = 10.39, 95% confidence interval (CI) = 3.15-34.29) and lymph node metastasis (HR = 5.58, 95% CI = 1.62-19.19) were independent risk factors for cancer-specific survival. CONCLUSIONS: In the initial surgery for GCTs, lymph node dissection can be omitted if the operative finding is pT1. In cases of pT2 or higher, lymph node dissection should be considered. Debulking is critical for achieving no gross residual tumor at the end of the surgery.

Tailored radical hysterectomy for locally advanced cervical cancer.

OBJECTIVE: The survival and prognostic factors for locally advanced cervical cancer treated with nerve-sparing Okabayashi-Kobayashi radical hysterectomy have not been elucidated. We aimed to evaluate the oncological outcomes of those patients after radical hysterectomy with adjuvant chemotherapy. METHODS: This retrospective cohort study was conducted from January 2002 to December 2011. Treatment was conducted at a single tertiary center in northern Japan. We used the Okabayashi-Kobayashi radical hysterectomy with lymphadenectomy. We applied unilateral nerve preservation for stage IIA/IIB cancer if there was a one-sided extension of the disease outside the cervix. Indication for adjuvant therapy was based on Sedlis criteria. High-risk was defined as evidence of lymph node metastasis, pathological parametrial invasion, and a positive/close surgical margin. The choice of adjuvant therapy was chemotherapy which consisted of paclitaxel and cisplatin. RESULTS: The study included 76 early-stage IB1 (≤4 cm) and IIA1 cervical cancer and 45 locally advanced stage IB2 (>4 cm), IIA2, and IIB disease treated consecutively. The median follow-up was 106 (range: 6-203) months. There were 18 (15%) patients with recurrence, with five of 76 in the early-stage (7%) and 13 of 45 in the locally advanced disease (29%) (P<0.001). For locally advanced cervical cancer, pT classification (P<0.001), lymph node metastasis (P=0.007), and histology (P=0.05) were associated with locoregional recurrence. The five-year locoregional recurrence rate in the locally advanced disease was 20% and 5% in the early-stage disease (P=0.01). The five-year disease-free survival in the locally advanced cervical cancer was 71% and 93% in the early-stage disease (P<0.001). The overall survival in locally advanced disease depended on the adeno-type histology and lymph node metastasis. CONCLUSION: The tailored use of nerve-sparing Okabayashi-Kobayashi radical hysterectomy with adjuvant chemotherapy based on tumor histology and lymph node metastasis may be a possible option as a treatment of locally advanced cervical cancer in selected patients.

Japan Society of Gynecologic Oncology guidelines 2017 for the treatment of uterine cervical cancer.

The Japan Society of Gynecologic Oncology (JSGO) Guidelines 2017 for the Treatment of Uterine Cervical Cancer are for the purpose of providing standard treatment strategies for cervical cancer, indicating treatment methods currently considered appropriate for cervical cancer, minimizing variances in treatment methods among institutions, improving the safety of treatment and prognosis of diseases, reducing the economic and psychosomatic burden of patients by promoting performance of appropriate treatment, and enhancing mutual understanding between patients and healthcare professionals. The guidelines were prepared through consensus of the JSGO Guideline Committee, based on careful review of evidence gathered through the literature searches and in view of the medical health insurance system and actual clinical practice situations in Japan. The guidelines comprise eight chapters and five algorithms. The main features of the 2017 revision are as follows: (1) evidence was collected using a search formula and with cooperation of the Japan Library Association. The bibliographical search formula was placed at the end of the book; (2) regarding clinical questions (CQs) where evidence or clinical inspection in Japan was lacking, opinions of the Guidelines Committee were described as "proposals for future directions"; (3) cervical intraepithelial neoplasia (CIN) 3 and adenocarcinoma in situ (AIS) were treated as a cervical precancerous lesion; (4) the CQs of endoscopic surgery, radical trachelectomy, and sentinel node biopsy were newly added in Chapter 3, "primary treatment for stage IB-II cervical cancer"; and (5) the CQ about hormone replacement therapy after cancer treatment was newly established. Each recommendation is accompanied by a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSGO Guidelines 2017 for the Treatment of Uterine Cervical Cancer.

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer.

BACKGROUND: Vulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese. OBJECTIVE: The JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan. METHODS: The guideline was created according to the basic principles in creating the guidelines of JSGO. RESULTS: The guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget's disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions. CONCLUSION: Overall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases.

Current status of tertiary debulking surgery and prognosis after secondary debulking surgery for recurrent Müllerian epithelial cancer in Japan: a retrospective analysis of 164 patients (KCOG-G1402).

BACKGROUND: This study aimed to evaluate the current status of secondary debulking surgery (SDS) and tertiary debulking surgery (TDS; performed for recurrence after SDS) and to assess the overall survival after recurrence of Müllerian epithelial cancer in Japan. We also evaluated the data of patients who underwent a fourth debulking surgery (i.e., quaternary debulking surgery (QDS)). METHODS: We conducted a retrospective study of 164 patients with recurrent Müllerian epithelial cancers (i.e., ovarian, tubal, and peritoneal cancers). The SDS was performed between January 2000 and September 2014 in 20 Japanese hospitals. Clinicopathological data were collected and analyzed. RESULTS: Of the 164 patients, 66 patients did not have a recurrence or died after SDS. Ninety-eight patients had a recurrence after SDS. Forty-three of the 98 patients underwent TDS; 55 of the 98 patients did not undergo TDS and were classified into the non-TDS group. The overall survival (OS) after SDS was significantly better in the TDS group than in the non-TDS group. The median OS after SDS was 123 and 42 months in the TDS group and non-TDS group, respectively. Of the 43 patients who received TDS, 11 patients were further treated with QDS. The median OS after SDS was 123 months for patients who underwent QDS. CONCLUSIONS: This multicenter study on the prognosis of post-SDS is apparently the first report on QDS in Japan. Patients undergoing TDS have a good prognosis, compared to patients in the non-TDS group. Novel drugs are being evaluated; however, debulking surgery remains a necessary treatment for recurrence.

A significant association between rs8067378 at 17q12 and invasive cervical cancer originally identified by a genome-wide association study in Han Chinese is replicated in a Japanese population.

In this study, associations between invasive cervical cancer and four cervical cancer susceptibility loci (rs13117307 at 4q12, rs8067378 at 17q12, and rs4282438 and rs9277952 at 6p21.32) in the Han Chinese population were investigated in a Japanese population. Human leukocyte antigen (HLA)-DPB1 alleles were also investigated for their association with cervical cancer risk in the Japanese population. After receiving written informed consent, 214 unrelated Japanese women with invasive cervical cancer and 288 cancer-free Japanese women were recruited, and DNA samples were obtained (study protocol approved by Institutional Review Board of Nagasaki University). Of the four single-nucleotide polymorphisms, rs8067378 showed a significant association with invasive cervical cancer (P=0.0071). Under a recessive model, the minor allele G of rs8067378 contributed to the risk of invasive cervical cancer (odds ratio=2.92, 95% confidence interval=1.40-6.36; P=0.0021). No association was detected between HLA-DPB1 alleles and cervical cancer risk in the Japanese population. In conclusion, we show for the first time, to the best of our knowledge, that an association between increased risk of invasive cervical cancer and rs8067378 in the Han Chinese population is replicated in a Japanese population. In addition, Japanese women with the GG genotype of rs8067378 are a candidate high-risk group for invasive cervical carcinoma.

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer.

The fourth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer was published in 2015. The guidelines contain seven chapters and six flow charts. The major changes in this new edition are as follows-(1) the format has been changed from reviews to clinical questions (CQ), and the guidelines for optimal clinical practice in Japan are now shown as 41 CQs and answers; (2) the 'flow charts' have been improved and placed near the beginning of the guidelines; (3) the 'basic points', including tumor staging, histological classification, surgical procedures, chemotherapy, and palliative care, are described before the chapter; (4) the FIGO surgical staging of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was revised in 2014 and the guideline has been revised accordingly to take the updated version of this classification into account; (5) the procedures for examination and management of hereditary breast and ovarian cancer are described; (6) information on molecular targeting therapy has been added; (7) guidelines for the treatment of recurrent cancer based on tumor markers alone are described, as well as guidelines for providing hormone replacement therapy after treatment.

Effect of labor on plasma concentrations and postpartum clearance of cell-free, pregnancy-associated, placenta-specific microRNAs.

OBJECTIVE: This study aimed to investigate the effect of labor on plasma concentrations of cell-free, pregnancy-associated, placenta-specific microRNAs (miRNAs) before and after delivery. METHOD: In the non-labor group (32 women), cesarean section (C/S) was performed before the beginning of labor. In the labor group (32 women), C/S was performed after the beginning of labor. Plasma concentrations of cell-free, pregnancy-associated, placenta-specific miRNAs (miR-515-3p, miR-517a, miR-517c, and miR-518b) were measured by real-time quantitative PCR. Each miRNA concentration was compared between the non-labor and labor groups. RESULTS: Before C/S, plasma concentrations of cell-free, pregnancy-associated, placenta-specific miRNAs in the labor group were significantly higher than those in the non-labor group (P = 0.001 for 515-3p, P = 0.002 for 517a, P = 0.001 for 517c, and P = 0.003 for 518b). Twenty-four hours after delivery, plasma concentrations of cell-free, pregnancy-associated, placenta-specific miRNAs in the labor group were significantly higher than those in the non-labor group (P = 0.002 for 515-3p, P = 0.017 for 517a, P = 0.043 for 517c, and P = 0.009 for 518b). CONCLUSION: The presence of labor affects cell-free, pregnancy-associated, placenta-specific miRNA levels in maternal plasma. Labor also affects postpartum clearance of these miRNAs 24 h after delivery.

Prospective risk of stillbirth in women with placental mesenchymal dysplasia.

AIM: The aim of this study was to provide better counsel to pregnant women with suspected placental mesenchymal dysplasia (PMD) regarding the risks of preterm birth and intrauterine fetal death. MATERIAL AND METHODS: We reviewed the outcomes of 109 PMD pregnancies with gestational week (GW) ≥ 24 abstracted from 63 reports in the English-language published reports, including two cases that we encountered recently. The prospective risk of stillbirth at GW N was defined as the number of women with stillbirth at GW ≥ N divided by the number of women giving birth at GW ≥ N. RESULTS: A total of 32 (29.4%) women experienced stillbirth at a median GW of 31 (range, 24-38). Preterm birth (GW < 37) occurred in 52 (67.5%) of the 77 live-born infants. Only 25 (22.9%) women had full-term (GW ≥ 37) live-born infants. The prospective risks of stillbirth were 29.4% (32/109), 27.5% (25/91), 20.9% (14/67) and 13.0% (6/46) for women who reached GW 24(+0) , 28(+0) , 32(+0) and 36(+0) respectively. CONCLUSION: As women with PMD are at markedly elevated risk of intrauterine fetal death, early admission to the hospital and intensive monitoring of fetal status should be considered, although whether this policy improves outcome has not been validated.

Circulating chromosome 19 miRNA cluster microRNAs in pregnant women with severe pre-eclampsia.

AIM: To clarify the association between circulating chromosome 19 miRNA cluster (C19MC) microRNAs in maternal plasma and severe pre-eclampsia. METHOD: Maternal blood samples (7 mL) at 27-34 weeks of gestation were obtained from 20 pregnant women with severe pre-eclampsia (sPE group) and from 20 uncomplicated pregnant women (NP group). Twenty cases of severe pre-eclampsia were classified into late onset (sPELO group; n = 14) and early onset (sPEEO group; n = 6). Plasma concentration of C19MC microRNAs (miR-518b, -1323, -516b, -516a-5p, -525-5p, -515-5p, -520 h, -520a-5p, -519d and -526b) was measured on quantitative real-time reverse transcription-polymerase chain reaction. RESULTS: The circulating levels of all 10 C19MC microRNAs in maternal plasma were significantly increased in the sPE group compared with the NP group. Plasma concentration of all 10 C19MC microRNAs tested was significantly increased in the sPEEO group compared with the NP group, while plasma concentration of nine miRNAs, except for miR-519d, was significantly increased in the sPELO group compared with the NP group. Of the 10 C19MC microRNAs measured, plasma concentration of eight miRNAs, except for miR-518b and miR-519d, was significantly increased in the sPEEO group compared with the sPELO group. CONCLUSIONS: Increased levels of C19MC microRNAs in maternal plasma are a characteristic phenomenon of established severe pre-eclampsia, and it has been shown for the first time that the upregulation of C19MC miRNAs occurred as a consequence of, not in advance of, the onset of pre-eclampsia.

Identification of KLF17 as a novel epithelial to mesenchymal transition inducer via direct activation of TWIST1 in endometrioid endometrial cancer.

Krüppel-like factor 17 (KLF17), a member of the KLF transcription factor family, has been shown to inhibit the epithelial-mesenchymal transition (EMT) and tumor growth. However, the expression, the cellular function and the mechanism of KLF17 in endometrioid endometrial cancer (EEC; a dominant type of endometrial cancer) remain elusive. Here, we report that among the KLF family members, KLF17 was consistently upregulated in EEC cell lines compared with immortalized endometrial epithelial cells. Overexpression of KLF17 in EEC cell lines induced EMT and promoted cell invasion and drug resistance, resulting in increased expression of TWIST1. In contrast, KLF17 suppression reversed EMT, diminished cell invasion, restored drug sensitivity and suppressed TWIST1 expression. Luciferase assays, site-directed mutagenesis and transcription factor DNA-binding analysis demonstrated that KLF17 transactivates TWIST1 expression by directly binding to the TWIST1 promoter. Knockdown of TWIST1 prevented KLF17-induced EMT. Consistent with these results, both KLF17 and TWIST1 levels were found to be elevated in EECs compared with normal tissues. KLF17 expression positively correlated with tumor grade but inversely correlated with estrogen and progesterone receptor expression. Thus, KLF17 may have an oncogenic role during EEC progression via initiating EMT through the regulation of TWIST1.

MicroRNA-106b modulates epithelial-mesenchymal transition by targeting TWIST1 in invasive endometrial cancer cell lines.

Type II endometrial carcinoma is an aggressive subtype of endometrial cancer (EC). TWIST1, a helix-loop-helix transcription regulator, is known to induce epithelial-mesenchymal transition (EMT) and promote tumor metastasis. MicroRNAs (miRNAs) also serve as important regulators of EMT and metastasis by regulating EMT-related genes. In this study, we sought to explore the role of TWIST1 in inducing EMT in representative type II EC cell lines, and to determine the miRNAs involved in regulating TWIST1 gene expression. Functional analysis suggested that TWIST1 contributes to the EMT phenotypes of EC cells, as evidenced by the acquisition of fibroblast-like properties, enhanced invasiveness, and induction of an EN-switch (downregulation of epithelial marker E-cadherin and upregulation of mesenchymal marker N-cadherin). Conversely, silencing of TWIST1 by siRNA inhibited cell invasion and the mesenchymal phenotype, which was accompanied by a reversion of the EN-switch. We also observed a novel post-transcriptional regulatory mechanism of TWIST1 expression mediated by miR-106b via its direct interaction with TWIST1 mRNAs at the 3'-untranslated region. Our data suggest that TWIST1 is a critical inducer of EMT in invasive EC cells and that miR-106b could suppress EC cell invasion by downregulating TWIST1 expression.

Single human papillomavirus 16 or 52 infection and later cytological findings in Japanese women with NILM or ASC-US.

The relationship between oncogenic human papillomavirus (HPV) infection and later cytological findings in the uterine cervix is unknown in women who were negative for intraepithelial lesion and malignancy (NILM) or atypical squamous cells of undetermined significance (ASC-US). This was investigated in this study in a Japanese population to determine the clinical utility of oncogenic (HPV) genotyping. The relative risk of progressive cytological findings 2 years after identification of oncogenic HPV infection was higher than in cases of non-oncogenic HPV infection (relative risk 3.827; 95% confidence interval (CI): 1.282-11.422), as well as in cases of negative HPV infection (relative risk 2.124; 95% CI: 1.451-3.110). Moreover, the relative risk of progression of cytological findings 2 years later in cases of HPV-16 infection was higher than in cases of HPV-52 infection (relative risk 2.094; 95% CI: 1.005-3.935). Therefore, the initial HPV-DNA genotype may be a potential predictive marker of later progression of cytological findings in the uterine cervix in cases of NILM or ASC-US.

Impact of FDG PET in optimizing patient selection for cytoreductive surgery in recurrent ovarian cancer.

PURPOSE: To investigate the impact of PET and PET/CT scanning on decision-making in management planning and to identify the optimal setting for selecting candidates for surgery in suspicious recurrent ovarian cancer. METHODS: A retrospective chart review was performed in patients with possible recurrent ovarian cancer after primary optimal cytoreduction and taxane/carboplatin chemotherapy who had undergone FDG PET or FDG PET/CT scans from July 2002 to August 2008 to help make treatment decisions. The analysis included 44 patients who had undergone a total of 89 PET scans. The positive PET scans were classified as follows. (1) localized (one or two localized sites of FDG uptake), (2) multiple (three or more sites of FDG uptake), (3) diffuse (extensive low-grade activity outlining serosal and peritoneal surfaces). RESULTS: Of the 89 PET scans, 52 (58.4%) led to a change in management plan. The total number of patients in whom cytoreductive surgery was selected as the treatment of choice increased from 12 to 35. Miliary disseminated disease, which was not detected by PET scan, was found in 22.2% of those receiving surgery. Miliary disseminated disease was detected in 6 of the 12 patients with recurrent disease whose treatment-free interval (TFI) was <12 months, whereas none of those with a TFI of ≥12 months had such disease (P = 0.0031). CONCLUSION: PET or PET/CT is useful for selecting candidates for cytoreductive surgery among patients with recurrent ovarian cancer. To avoid surgical attempts in those with miliary dissemination, patients with a TFI of ≥12 months are the best candidates for cytoreductive surgery.

Identification of endometrioid endometrial carcinoma-associated microRNAs in tissue and plasma.

OBJECTIVE: This study aimed to identify a set of endometrioid endometrial carcinoma EEC-associated microRNAs (miRNAs) in tissue and plasma, and evaluate their clinical significance. METHODS: A set of EEC-associated miRNAs in tissue and plasma was identified by next-generation sequencing (NGS), which could enable in-depth characterization of the global repertoire of miRNAs. RESULTS: NGS identified 11 candidate EEC-associated miRNAs. Quantitative reverse-transcriptase PCR identified 8 EEC-associated miRNAs in tissue (upregulated: miR-499, miR-135b, miR-205, downregulated: miR-10b, miR-195, miR-30a-5p, miR-30a-3p and miR-21). Expression of hsa-miR-499 in International Federation of Gynecology and Obstetrics (FIGO) Stage IA and Grade 1 tissues was significantly lower than in others (FIGO Stage IB or more advanced, and Grade 2 or 3). By receiver operating characteristic (ROC) curve analysis, compared with single EEC-associated miRNA, two miRNA signatures (miR135b/miR195 and miR135b/miR30a-3p) could distinguish between EEC and normal endometrial tissue samples yielding a high area under the curve (AUC) of 0.9835 [95% confidence interval (CI): 0.9677-1.0], and 0.9898 (95% CI: 0.9677-1.0), respectively. As possible non-invasive markers for EEC, four EEC-associated miRNAs (increased level: miR-135b and miR-205, decreased-level: miR-30a-3p and miR-21) in plasma were identified. Circulating levels of three EEC-associated miRNAs (miR-135b, miR-205 and miR-30a-3p) in plasma were significantly decreased after hysterectomy. ROC curves analysis revealed that miR-135b and miR-205 levels in plasma yielded AUCs of 0.9722 (95% CI: 0.913-1.0) and 1.0 (95% CI: 1.0-1.0), respectively. CONCLUSION: Measurement of tissue and plasma EEC-associated miRNAs may be useful for early detection, diagnostic, and follow-up tests for EEC.

Predominantly placenta-expressed mRNAs in maternal plasma as predictive markers for twin-twin transfusion syndrome.

OBJECTIVE: This study aimed to identify a set of predominantly placental (PP) mRNAs, which are associated with later-developing twin-to-twin transfusion syndrome (TTTS). METHOD: First, out of 50 PP mRNAs we previously reported, we select target mRNAs that are ordinarily detectable in maternal plasma. Plasma concentrations of these PP mRNAs were measured in monochorionic diamniotic twin (MCDA-T) pregnancies complicated by TTTS later (n = 11) and in uncomplicated MCDA-T pregnancies (n = 17). Finally, the diagnostic values of the PP mRNAs in plasma were evaluated. RESULTS: From 50 PP mRNAs, nine [human placental lactogen (hPL); pregnancy-specific glycoproteins 2 (PSG2); human pregnancy-specific glycoproteins 3 (PSG3); syncytin; syncytin 2; retinoic acid-induced 14; A disintegrin and metalloproteinase domain-containing protein 12 (ADAM12); chorionic glycoprotein hormones, alpha polypeptide; and chorionic glycoprotein hormones, and beta polypeptide] were selected as target mRNAs. Changes in six PP mRNAs [increased hPL, PSG2, and PSG3 and decreased syncytin, syncytin2, and ADAM12] in maternal plasma were detected in MCDA-T pregnant women who subsequently developed TTTS. Finally, mRNA signatures gave elevated AUCs (hPL/PSG2: 0.8717; hPL/PSG3: 0.8449; hPL/ADAM12: 0.8396) compared with single hPL mRNA. CONCLUSION: Quantitative aberration of plural cell-free PP mRNAs in maternal plasma precedes the appearance of clinically apparent TTTS. This suggests that pathophysiological changes in the placenta are associated with morbid conditions of TTTS.

Gestational weight gain according to number of fetuses in Japanese women.

AIM: It is unknown whether weekly maternal weight gain differs between Japanese women with singleton, twin, and triplet pregnancies. METHODS: Gestational weight gain defined as net weight gain during pregnancy was analyzed in 135,036 pregnant Japanese women, including 128,838 with singletons, 5573 with twins, and 132 with triplets, who gave birth at ≥22 weeks of gestation between 2007 and 2009. Weekly weight gain was defined as follows: gestational weight gain÷[gestational week (GW) at Delivery-2]. RESULTS: Length of gestation (weeks, mean±SD) decreased significantly (38.2±2.6, 35.3±3.0, and 32.7±2.8) with increasing number of fetuses, while overall gestational weight gain (kg) was significantly smaller in women with singletons than in those with either twins or triplets (9.6±4.4 vs. 10.9±4.8 or 10.9±5.2, respectively). Thus, weekly maternal weight gain (kg/week) increased significantly with increasing number of fetuses (0.26±0.12, 0.33±0.13, and 0.35±0.16). Among women with delivery at or after GW 34, difference in gestational weight gain (kg) was prominent between the three groups (9.8±4.4, 11.4±4.7, and 13.0±5.1 for singleton, twin, and triplet pregnancies, respectively, P<0.001 between any two groups). CONCLUSIONS: Weekly maternal weight gain increases with increasing number of fetuses. Our figures may be useful for advising Japanese women with multifetal pregnancies regarding gestational weight gain.