Changes in the number of babies born with Down syndrome in Japan.

AIM: The number of babies born with Down syndrome has changed in recent years because of widespread availability of prenatal screening and advanced maternal age at delivery. In Japan, which has no public institutions that record data on babies born with chromosomal abnormalities (including Down syndrome), the accurate number remains unknown. METHODS: The Japan Association of Obstetricians and Gynecologists Birth Defects Monitoring Program (hereafter the JAOG Program) is the only national survey of congenital anomalies in Japan. Using data from this survey and vital statistics, we investigated the changes in the number of babies born with Down syndrome in Japan from 2006 to 2019. RESULTS: On performing linear regression analysis with the proportion of babies born with Down syndrome as the response variable, and the proportion of mothers giving birth at the age of 35 years or older as the explanatory variable, the regression coefficient was 0.0054 (p < 0.001). The proportion of mothers giving birth at the age of 35 years or older was useful for predicting the proportion of babies born with Down syndrome. This proportion has increased since 2006 but has remained almost unchanged since 2015. In 2019, it was 1/734. CONCLUSIONS: This study revealed that the proportion of mothers giving birth at the age of 35 years or older strongly affected the proportion of babies born with Down syndrome. We assume that the proportion of babies is slightly affected by the increased number of pregnant women currently undergoing prenatal screening after the introduction of noninvasive prenatal genetic testing in 2013.

25-Hydroxyvitamin D profiles and maternal bone mass during pregnancy and lactation in Japanese women.

Vitamin D deficiency is observed worldwide and represents a health hazard for mothers, infants and elderly persons. We know that many young Japanese women experience vitamin D insufficiency; however, there is a lack of knowledge regarding the serum 25-hydroxyvitamin D [25(OH)D] profile of pregnant Japanese women and of the association between maternal 25(OH)D level and maternal bone mass during pregnancy and lactation. In this longitudinal study, 160 pregnant Japanese women were enrolled; of them, 68 have been followed-up from the first trimester through at least 1 year of breast-feeding. We estimated serum 25(OH)D levels, intact PTH levels, calcaneus quantitative ultrasound (QUS: T score) scores, bone mineral density at the distal one-third of the radius, dietary intakes according to the Food Frequency Questionnaire, and sunlight exposure times. We found that Vitamin D deficiency is prevalent in Japanese women, irrespective of pregnancy or lactation, and our analysis suggested that 25(OH)D levels and BMI in the first trimester were related to the lactating women's bone mass from after delivery to 1 year after delivery.

Aberrant Nuclear Localization of aPKCλ/ι is Associated With Poorer Prognosis in Uterine Cervical Cancer.

We previously reported that aberrant expression of atypical protein kinase C λ/ι (aPKCλ/ι) in low-grade squamous intraepithelial uterine cervix lesions was associated with an increased risk of progression to higher grade. This study aimed to investigate aPKCλ/ι expression patterns in cervical squamous cell carcinoma (SCC) and its association with disease progression. We immunohistochemically assessed aPKCλ/ι expression in 168 SCC samples and 13 normal uterine cervix samples. In 69.0% of SCC cases, aPKCλ/ι was expressed more abundantly than in normal epithelium, but there was no significant association between aPKCλ/ι intensity and disease progression (P=0.087, Cochran-Mantel-Haenszel test). aPKCλ/ι in normal cervical epithelium was confined to the cytoplasm or intercellular junctions. In contrast, aPKCλ/ι was predominantly localized within the nucleus in 36.9% of SCC samples (P<0.001, χ test), and the prevalence was significantly increased relative to advanced tumor stage (P<0.001, Cochran-Mantel-Haenszel test). Moreover, patients with SCC with aPKCλ/ι nuclear localization had worse prognoses than those with cytoplasmic localization (P<0.001, log-rank test). aPKCλ/ι localization differed between the intraepithelial lesion and adjacent invasive cancer in 40% of cases, while the expression pattern was similar between primary and matched metastatic tumors. In conclusion, aPKCλ/ι nuclear localization in cervical cancer is associated with tumor progression and worse prognosis. This is the first report to show aberrant nuclear aPKCλ/ι localization in a subgroup of cervical cancer patients and its association with worse prognosis.

Prevalence of Congenital Anomalies in the Japan Environment and Children's Study.

BACKGROUND: The aims of the present report were to estimate the prevalence of congenital anomalies (CAs) among infants in Japan using data from the Japan Environment and Children's Study (JECS) and to evaluate the validity of CA classification within JECS. METHODS: Data on CAs were collected at delivery and at age 1 month from the medical records of 101,825 infants at 15 regional centers. The analyses focused on 61 CAs, selected on the basis of reported associations with environmental exposure. Prevalence per 10,000 pregnancies (including miscarriages, stillbirths, and live births) was stratified according to four reporting patterns (at delivery, at age 1 month, at either, and at both). To evaluate the accuracy of observed CA prevalence, the medical records of 179 cases from a single JECS regional center underwent independent, retrospective re-evaluation. RESULTS: The prevalence of major CAs in four reporting patterns (at delivery, at age 1 month, at either, and at both) was 2.4, 2.6, 3.5, and 1.4 for myelomeningocele/spina bifida; 4.3, 4.2, 5.3, and 3.2 for cleft palate; 18.1, 17.4, 19.5, and 15.1 for cleft lip with or without cleft palate; 73.4, 100.3, 120.8, and 52.8 for congenital heart disease; and 10.5, 14.1, 15.0, and 9.6 for Down's syndrome, respectively. In the subsample re-evaluation, CA diagnoses were confirmed for 92.7%, 93.3%, 90.5%, and 97.8% of cases in the four reporting patterns (at delivery, at age 1 month, at either, and at both), respectively. CONCLUSIONS: The present report generated reliable data concerning the prevalence of major CAs in JECS.

Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT.

OBJECTIVE: To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results. METHODS: A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases. RESULTS: Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (<4%), and 18 (16.4%) cases including those with a maternal malignancy, were found to have altered genomic profile. Approximately half of the cases with nonreportable results had borderline z score. Among the women with nonreportable results because of altered genomic profile, the success rate of retesting using a second blood sampling was relatively low (25.0%-33.3%). Thirteen (11.8%) of the women with nonreportable results had required hypodermic heparin injection. CONCLUSIONS: The classification of nonreportable results using cfDNA analysis is important to provide women with precise information and to reduce anxiety during pregnancy.

Current knowledge of and attitudes toward human papillomavirus-related disease prevention among Japanese: A large-scale questionnaire study.

AIM: The human papillomavirus (HPV) vaccination rate in Japan fell to nearly 0% following widespread coverage of possible adverse events. Developing a next approach to promote the effective prevention of HPV-related diseases including cervical cancer (CC) in Japan requires comprehensive understanding of knowledge and attitudes regarding CC prevention, HPV infection and HPV vaccination among the population including laypersons and medical professions in Japan. METHODS: A questionnaire survey was administered in a wide variety of settings in Japan. The questionnaire contained items on knowledge about CC, HPV infection and HPV vaccination; awareness of the HPV vaccine's effectiveness and associated adverse events; and attitudes toward the HPV vaccination for their daughters and for men/boys. RESULTS: Of 3033 targeted people, complete survey responses were received from 1182 men and 1602 women (total: 2784). The male laypersons' group had significantly lower knowledge than did the female laypersons' group (adjusted odds ratio, aOR = 3.86, P < 0.001). Compared with the male laypersons' group, the female laypersons' group tended to have less positive attitudes toward HPV vaccination for their daughters (aOR = 0.78, P = 0.006), but the female laypersons' group showed more positive attitudes toward vaccinating men/boys (aOR = 1.93, P < 0.001). CONCLUSION: The survey results indicated that men in Japan generally lacked knowledge and awareness of HPV-related diseases and their prevention. However, women had more negative attitudes toward HPV vaccination for their daughters than did men. Increasing male involvement in HPV prevention and changing women's perceptions of the HPV vaccine are essential steps to increase the HPV vaccination rate.

Maternal age-specific risk for trisomy 21 based on the clinical performance of NIPT and empirically derived NIPT age-specific positive and negative predictive values in Japan.

The data collected by nation-wide study of noninvasive prenatal genetic testing (NIPT) for trisomy 21 from 21,610 pregnant women with advanced maternal age in Japan were reported. Among 188 NIPT-positive cases, 180 cases were true positive. The incidence of aneuploidy according to maternal age was estimated using a state-space model. Although, the frequency of trisomy increased exponentially with maternal age as previously reported, the maternal age-specific risk for trisomy 21 that was based on the clinical performance of NIPT was lower than the predicted risk in previous Western cohorts based on the data from invasive prenatal testing (Bayesian two-sided tail-area probability P = 0.0156). The empirical positive predictive value (PPV) of NIPT is likely to turn out higher than that of the theoretical PPV calculated from the sensitivity/specificity of the test and the incidence of trisomy 21 from this study.

Correction: Maternal age-specific risk for trisomy 21 based on the clinical performance of NIPT and empirically derived NIPT age-specific positive and negative predictive values in Japan.

Since the advance online publication of this article, the authors of the above paper have noticed errors in the list of authors and affiliations. The article with correct author information now appears in this issue.

Correction: Nationwide survey for current clinical status of amniocentesis and maternal serum marker test in Japan.

Since the publication of this paper, the authors noticed that Yosuke Fujii was assigned to the incorrect affiliation. The affiliation information is provided correctly, above.

Comparison of plasma amino acid profile-based index and CA125 in the diagnosis of epithelial ovarian cancers and borderline malignant tumors.

BACKGROUND: We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths. METHODS: API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves. RESULTS: The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p < 0.05). At the API cutoff level of 6.0, API and CA125 had equal positive rates of detecting cancers and borderline malignancies (API, 0.71 vs. CA125, 0.74; p = 0.84) or cancers alone (API, 0.73 vs. CA125, 0.85; p = 0.12). However, API had a significantly lower detection rate of benign endometriotic cysts (0.35; 95 % CI, 0.21-0.52) compared with that of CA125 (0.65; 95 % CI, 0.48-0.79) (p < 0.05). CONCLUSIONS: API is an effective new tumor marker to detect ovarian cancers and borderline malignancies with a low false-positive rate for endometriosis. A large-scale prospective clinical study using the cutoff value of API determined in this study is warranted to validate API for practical clinical use.

Short- and long-term complications and the impact on quality of life after cervical conization by harmonic scalpel.

AIM: The incidence of non-obstetrical complications after cervical conization is low, and women receive minimal postsurgical attention. In this study, we investigated whether women felt any discomfort after undergoing conization by harmonic scalpel, one of the hot-knife devices widely used in Japan. METHODS: Eighty-eight women aged 20-47 years who were still experiencing menstrual cycles and had undergone harmonic conization participated in a questionnaire survey regarding perisurgical complications and postsurgical changes in gynecological issues. Correlations between the occurrence of postoperative complications and clinical characteristics were analyzed. RESULTS: Regarding the complications immediately after the surgery, 37 women (45.1%) complained of postoperative bleeding that was heavier than their usual menstrual bleeding, and 14 (18.2%) reported that the postsurgical bleeding was greater than they had expected. Regarding long-term gynecological changes after conization, 27 women (30.7%) reported that the duration of menstrual bleeding had increased after the surgery, 20 (22.7%) indicated that pain during menstruation had changed, and 40 (45.5%) stated that the amount of menstrual bleeding had changed. Irregular genital bleeding outside of menstruation appeared in 23 women (26.4%). Additionally, 24 (27.6%) of the women reported that the conization procedure negatively impacted their quality of life. Finally, the occurrence of long-term atypical bleeding after the surgery was significantly correlated with the thickness and circumference of the tissue specimen. CONCLUSION: Several women experienced a significant change in quality of life after harmonic conization. Women who undergo conization should receive a comprehensive preoperative overview of the procedure and attentive postsurgical care.

Evaluation of endocervical curettage with conization in diagnosis of endocervical lesions.

AIM: Endocervical curettage (ECC) at the time of conization has been reported to be effective for diagnosing cervical intraepithelial neoplasia and/or early stage cervical cancer. We aimed to verify the accuracy of ECC with conization. METHODS: We retrospectively analyzed the records of 540 patients with suspected neoplastic cervical lesions who underwent conization at the Yokohama City University Hospital from January 2008 to December 2015. To validate the effectiveness of ECC for evaluating endocervical lesions, histopathologic findings from ECC samples were compared with those from endocervical specimens obtained by conization. In patients who subsequently underwent hysterectomy, specimens of residual endocervical stump lesions were compared with the specimens obtained by ECC. RESULTS: ECC was performed in 58.9% of patients who underwent conization. Positive findings were only observed in 7.9%, while negative findings were found in 67.3% of ECC samples; however, 24.8% of the samples were inadequate for diagnosis. None of the patients had an upgraded diagnosis according to ECC results. The sensitivity of ECC in predicting endocervical stump lesions that were identified by conization specimens was 25.0%, the specificity was 94.2% and the positive predictive value was 55.0% (κ = 0.238; P < 0.001). ECC samples yielded a sensitivity of 42.9%, a specificity of 83.9%, and positive predictive value of 54.5% (κ = 0.284; P = 0.053) in predicting residual endocervical lesions in the uterus. CONCLUSIONS: As it offers low sensitivity and positive predictive value, ECC at the time of conization is of limited benefit for evaluating endocervical lesions.

Current status of non-invasive prenatal testing in Japan.

AIM: The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. METHODS: Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. RESULTS: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. CONCLUSION: Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

Nationwide survey for current clinical status of amniocentesis and maternal serum marker test in Japan.

Prenatal testing has been provided in Japan over the past several decades. However, it is difficult to assess the clinical status of amniocentesis (AC) and maternal serum markers (MSM) because obstetricians can perform these tests without registration. This study aims to investigate the current clinical status of AC and MSM in Japan. We conducted a questionnaire study that was intended for a total of 5622 Japanese obstetrics/gynecology facilities during October 2013 to January 2014. The response rate was 40.8% (2295/5622). Of the 2295 facilities, 864 performed MSM (37.7%), 619 performed AC (27.0%) and 412 performed both (18.0%). The average number of MSM tests was 2.0 per month (range 0-52), and the average number of AC tests was 2.4 per month (range 0-30). Involvement of genetic professionals, such as clinical geneticists (CGs) and certified genetic counselors (CGCs), contribute to a content-rich explanation and management of difficult issues and lengthened the explanation time. Nevertheless, relatively few facilities employed these specialists (MSM: 96/864 and AC: 128/619). This is the first study to highlight the current clinical status of AC and MSM tests in Japan. Active involvement of CGs and CGCs can provide more appropriate genetic counseling for prenatal tests.

Fetal cell-free DNA fraction in maternal plasma is affected by fetal trisomy.

The purpose of this noninvasive prenatal testing (NIPT) study was to compare the fetal fraction of singleton gestations by gestational age, maternal characteristics and chromosome-specific aneuploidies as indicated by z-scores. This study was a multicenter prospective cohort study. Test data were collected from women who underwent NIPT by the massively parallel sequencing method. We used sequencing-based fetal fraction calculations in which we estimated fetal DNA fraction by simply counting the number of reads aligned within specific autosomal regions and applying a weighting scheme derived from a multivariate model. Relationships between fetal fractions and gestational age, maternal weight and height, and z-scores for chromosomes 21, 18 and 13 were assessed. A total of 7740 pregnant women enrolled in the study, of which 6993 met the study criteria. As expected, fetal fraction was inversely correlated with maternal weight (P<0.001). The median fetal fraction of samples with euploid result (n=6850) and trisomy 21 (n=70) were 13.7% and 13.6%, respectively. In contrast, the median fetal fraction values for samples with trisomies 18 (n=35) and 13 (n=9) were 11.0% and 8.0%, respectively. The fetal fraction of samples with trisomy 21 NIPT result is comparable to that of samples with euploid result. However, the fetal fractions of samples with trisomies 13 and 18 are significantly lower compared with that of euploid result. We conclude that it may make detecting these two trisomies more challenging.

A survey on awareness of genetic counseling for non-invasive prenatal testing: the first year experience in Japan.

The purpose of this study is to summarize the results from a survey on awareness of genetic counseling for pregnant women who wish to receive non-invasive prenatal testing (NIPT) in Japan. As a component of a clinical study by the Japan NIPT Consortium, genetic counseling was conducted for women who wished to receive NIPT, and a questionnaire concerning both NIPT and genetic counseling was given twice: once after pre-test counseling and again when test results were reported. The responses of 7292 women were analyzed. They expressed high satisfaction with the genetic counseling system of the NIPT Consortium (94%). The number of respondents who indicated that genetic counseling is necessary for NIPT increased over time. Furthermore, they highly valued genetic counseling provided by skilled clinicians, such as clinical geneticists or genetic counselors. The vast majority (90%) responded that there was sufficient opportunity to consider the test ahead of time. Meanwhile, women who received positive test results had a poor opinion and expressed a low-degree satisfaction. We confirmed that the pre-test genetic counseling that we conducted creates an opportunity for pregnant women to sufficiently consider prenatal testing, promotes its understanding and has possibilities to effectively facilitate informed decision making after adequate consideration. A more careful and thorough approach is considered to be necessary for women who received positive test results.

A preoperative risk-scoring system to predict lymph node metastasis in endometrial cancer and stratify patients for lymphadenectomy.

OBJECTIVE: This study aimed to validate the preoperative scoring system adopted in the Kanagawa Cancer Center (KCC) to stratify endometrial cancer patients for lymphadenectomy according to the risk of developing lymph node metastasis (LNM). METHODS: The records of 432 and 221 uterine cancer patients treated in the KCC and Yokohama City University (YCU), respectively, were retrospectively analyzed. The KCC classified patients for LNM risk based on tumor volume, myometrial invasion, histological grade, and serum CA125 levels, while YCU used only myometrial invasion. Lymphadenectomy was omitted for 156 patients with 0 LNM risk, while pelvic lymphadenectomy (PLX) or PLX with para-aortic lymphadenectomy (PLAX) were performed for those with low and high LNM risk, respectively. The predicted and actual LNM rates were compared between the KCC and YCU patients, and cancer recurrence and overall survival were analyzed. RESULTS: There was no difference in survival between patients with LNM score 0 who were or were not treated with lymphadenectomy. None (0%) developed LNM and only 1 (0.6%) had recurrence. Patients who underwent PLX but not PLAX (low LNM score) had a low tumor recurrence rate in the para-aortic nodes (1.3%). The KCC scoring system was significantly more accurate than the YCU system in predicting LNM in the high-risk group (P<0.05) and demonstrated that PLAX was unnecessary in almost 50% of the YCU cases. CONCLUSION: The KCC preoperative scoring system is useful to predict LNM risk, and thereby prevent unnecessary lymphadenectomy or to determine its extent in endometrial cancer patients.

Phase II study of concurrent chemoradiotherapy with weekly cisplatin and paclitaxel in patients with locally advanced uterine cervical cancer: The JACCRO GY-01 trial.

OBJECTIVE: A multicenter phase II trial was conducted to assess the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with weekly cisplatin (CDDP) and paclitaxel (PTX) in patients with locally advanced uterine cervical cancer. METHODS: Patients with FIGO stage III-IVA uterine cervical cancer without para-aortic lymphadenopathy were enrolled. Patients received definitive radiotherapy (RT) consisting of external beam whole-pelvic RT and high-dose-rate intracavitary brachytherapy. The cumulative linear quadratic equivalent dose was 62-65Gy prescribed at point A. weekly CDDP at 30mg/m(2) and PTX at 50mg/m(2) were administered concurrently with RT for ≥5 courses. RESULTS: Sixty-eight of the 70 registered patients were eligible. The complete response rate was 76.5% (95% confidence interval [CI], 66.4-86.6%). With a median follow-up of 27months (range, 7.9-33.5), the 2-year cumulative progression-free survival and the 2-year cumulative overall survival rates were 83.8% (95% CI, 75.1-92.6%) and 92.7% (95% CI, 86.4-98.9%), respectively. The pelvic cumulative disease progression-free and the 2-year cumulative distant metastasis rates were 89.6% (95% CI, 82.3-96.9%) and 13.2% (95% CI, 5.2-21.3%), respectively. The 2-year cumulative late complication rates were 25% for all grades, 13.2% for grade 1, 5.9% for grade 2, 2.9% for grade 3, and 2.9% for grade 4. CONCLUSIONS: For locally advanced cervical cancer, CCRT with weekly CDDP 30mg/m(2) and PTX at 50mg/m(2) demonstrated favorable antitumor activity, and was feasible and safe with respect to the protocol-specified serious adverse reactions and events. Evaluation of this regimen in phase III trials is warranted.

Aberrant Expression of the Cell Polarity Regulator aPKCλ/ι is Associated With Disease Progression in Cervical Intraepithelial Neoplasia (CIN): A Possible Marker for Predicting CIN Prognosis.

Atypical protein kinase C λ/ι (aPKCλ/ι) is a regulator of epithelial cellular polarity. It is also overexpressed in several cancers and functions in cell proliferation and invasion. Therefore, we hypothesized that aPKCλ/ι may be involved in development and progression of cervical intraepithelial neoplasia (CIN), the precancerous disease of cervical cancer induced by human papillomavirus. To do this, we investigated the relationship between aPKCλ/ι expression and CIN. aPKCλ/ι expression level and subcellular localization were assessed in 192 CIN biopsy samples and 13 normal epithelial samples using immunohistochemistry. aPKCλ/ι overexpression (normal epithelium, 7.7%; CIN1, 41.7%; CIN2/3, 76.4%) and aPKCλ/ι nuclear localization (normal epithelium, 0.0%; CIN1, 36.9%; CIN2/3, 78.7%) were higher in CIN samples than normal samples (P<0.05), suggesting that CIN grade is related to aPKCλ/ι overexpression and nuclear localization. Then, 140 CIN cases were retrospectively analyzed for 4-yr cumulative disease progression and regression rates using the Cox proportional hazards model. CIN1 cases with aPKCλ/ι overexpression or aPKCλ/ι nuclear localization had a higher progression rate than CIN1 cases with normal aPKCλ/ι expression levels or cytoplasmic localization (62.5% vs. 9.7% and 63.1% vs. 9.4%, respectively; P<0.001). Multivariate analysis indicated that human papillomavirus types 16 and 18, aPKCλ/ι overexpression (hazard ratio=4.26; 95% confidence interval, 1.50-12.1; P=0.007), and aPKCλ/ι nuclear localization (hazard ratio=3.59; 95% confidence interval, 1.24-10.4; P=0.019) were independent risk factors for CIN1 progression. In conclusion, aPKCλ/ι could be useful for the therapeutic management of patients with CIN, particularly those with non-human papillomavirus 16/18 types.

Effect of transarterial embolization for post-partum hemorrhage on subsequent pregnancy.

Although pregnancy after transarterial embolization (TAE) has occasionally been reported, gelatin sponge was used as the embolic agent in most of these cases. Reports on the effect of TAE with permanent embolic agents such as N-butyl cyanoacrylate or coil on subsequent pregnancies are rare. We describe placenta accreta associated with difficult hemostasis in two patients who became pregnant after TAE with permanent embolic agents. In pregnancy after TAE with permanent embolic agents, placenta accreta occurs frequently and well-developed collateral vessels are highly likely, resulting in difficult hemostasis. Although the acceptability of pregnancy after TAE with permanent embolic agents is controversial, patients should be informed that pregnancy is extremely high risk.