Recent Prevalence of Human T-cell Leukemia Virus Type 1 Carrier Associated with Horizontal Transmission in Pregnant Japanese Women.

The current study was conducted to examine the number of human T-cell leukemia virus type 1 (HTLV-1) carriers and how horizontal transmission affected the prevalence of HTLV-1 carriers among pregnant Japanese women in 2019. We requested 2,214 obstetrical facilities to provide information on HTLV-1 tests for pregnant women who delivered in 2019. The estimated number of HTLV-1 carriers among pregnant Japanese women was 952. At least 10% or more of the carriers acquired HTLV-1 through horizontal transmission.

Current status of cervical cytology during pregnancy in Japan.

In Japan, uterine cancer screening during pregnancy is subsidized by public funds. We examined the current status of the results of cervical cytology conducted during pregnancy in Japan. We requested 2,293 obstetrical facilities to provide information on cervical cytology in pregnant women who delivered between October 2018 and March 2019. A total of 1,292 obstetrical facilities responded, with valid information on a total of 238,743 women. The implementation rate of cervical cytology during pregnancy was 86.8% in Japan. The prevalence of abnormal cervical cytology during pregnancy was 3.3% in total and 4.9% using a spatula/brush with liquid-based cytology (LBC). The prevalence of positive high-risk human papillomavirus (HPV) in teenagers with atypical squamous cells of undetermined significance (ASC-US) was significantly higher than women of other ages (p < 0.01). Because HPV vaccine coverage has dropped to less than 1% in Japan, a further study with various conditions will be needed to improve the accuracy of cervical cancer screening during pregnancy.

Effectiveness of human papillomavirus vaccination in young Japanese women: a retrospective multi-municipality study.

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan's HPV vaccination rate dropped from 70% to less than 1% in 2017.We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of high-grade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

Current status of syphilis in pregnant women in Japan.

We examined the current status of syphilis-infected pregnant Japanese women, according to the results of syphilis screening and confirmation tests of women who gave birth in Japan between October, 2015 and March, 2016. We requested 2458 obstetrical facilities to provide information of syphilis screening tests and 78.1% of them responded. Considering the response rate and the rate of implementation of confirmation tests, the number of syphilis-infected pregnant Japanese women was estimated to be 250 (1/4022) per year.

The use of balloons for uterine cervical ripening is associated with an increased risk of umbilical cord prolapse: population based questionnaire survey in Japan.

BACKGROUND: To clarify whether the use of balloons for cervical ripening is associated with the incidence of umbilical cord prolapse. METHODS: A postal questionnaire survey was distributed in Japan. Cases of umbilical cord prolapse occurring during labor in association with the use of balloons for cervical ripening between 2007 and 2011 in Japan were analyzed. RESULTS: Answers from 942 institutions were obtained. The subjects included 369 patients with fore-lying or prolapse of the umbilical cord among a total of 2,037,460 deliveries. Among the singleton vertex cases, fore-lying or prolapse of the umbilical cord during labor were observed in 88 (0.005%) of 1,891,189 deliveries not associated with the use of balloons for cervical ripening and in 93 (0.064%) of 146,271 deliveries associated with the use of balloons for cervical ripening (Odds ratio 13.67, 95% confidence interval 10.21, 18.30). All types of balloons were significantly associated with the occurrence of fore-lying or prolapse of the umbilical cord. A total of 39% of cases of umbilical cord prolapse occurred during manual or spontaneous balloon removal, while 53% of cases occurred after a while not directly associated with balloon removal. CONCLUSION: The risk of umbilical cord prolapse was significantly increased during the use of balloons for cervical ripening, especially in cases involving the use of disk-type and ball-type balloons filled with large amounts of water.

Current status of HTLV-1 carrier in Japanese pregnant women.

We examined the current status of human T-cell leukemia virus type 1 (HTLV-1) carrier in Japanese pregnant women, according to the results of HTLV-1 screening and confirmation tests of women who gave birth in Japan in 2011. We requested 2642 obstetrical facilities to provide information of HTLV-1 tests and 71.3% of them responded. Considering the response rate and the rate of implementation of confirmation tests, the number of HTLV-1 carrier in Japanese pregnant women was estimated to be 1620 (0.16%) per year.

Induction of senescence by progesterone receptor-B activation in response to cAMP in ovarian cancer cells.

OBJECTIVE: Progesterone receptor (PR) expression is a favorable prognostic marker in ovarian cancer. We previously demonstrated that the induction of PR-B by treatment with cAMP was associated with G0/G1 arrest of the cell cycle and growth inhibition in NIH 3T3 cells. In this study, we examined the effect of cAMP treatment on cell growth in Ras-transformed NIH3T3 cells and ovarian cancer cells. METHODS: 1) The levels of PR-B and cell cycle associated proteins (p21, p27 and Rb) following treatment with cAMP in the Ras-transformed NIH3T3 cells (K12V) and ovarian cancer cell lines (SKOV cells) were investigated by Western blots. 2) The effects of PR overexpression following treatment with cAMP or after infection of an adenovirus expressing PR-B on cell growth and tumorigenicity in a soft agar culture were examined. RESULTS: 1) Treatment with cAMP increased PR-B and p27 levels in K12V cells and inhibited cell growth by inducing premature senescence. Induction of senescence was specific to the transformed cells. 2) In SKOV cells, treatment with cAMP induced PR-B, p27 and p21 expression, reduced the level of phosphorylated Rb, caused accumulation of cells in the G0/G1 fraction of the cell cycle, and induced senescence. 3) Both anchorage-dependent and -independent SKOV cell growths were inhibited by cAMP treatment. 4) Induction of both the expression and transcriptional activity of PR-B is critical for the induction of senescence and suppression of tumorigenicity. CONCLUSION: Treatment of cAMP, through activation of PR-B, induced senescence and suppressed tumorigenicity in ovarian cancer cells.

NKG2A inhibits invariant NKT cell activation in hepatic injury.

Activation of invariant NKT (iNKT) cells in the liver is generally regarded as the critical step for Con A-induced hepatitis, and the role of NK cell receptors for iNKT cell activation is still controversial. In this study we show that blockade of the NKG2A-mediated inhibitory signal with antagonistic anti-NKG2A/C/E mAb (20d5) aggravated Con A-induced hepatitis in wild-type, Fas ligand (FasL)-mutant gld, and IL-4-deficient mice even with NK cell and CD8 T cell depletion, but not in perforin-, IFN-gamma-, or IFN-gamma- and perforin-deficient mice. Consistently, 20d5 pretreatment augmented serum IFN-gamma levels and perforin-dependent cytotoxicity of liver mononuclear cells following Con A injection, but not their FasL/Fas-dependent cytotoxicity. However, blockade of NKG2A-mediated signals during the cytotoxicity effector phase did not augment cytotoxic activity. Activated iNKT cells promptly disappeared after Con A injection, whereas NK1(-) iNKT cells, which preferentially expressed CD94/NKG2A, predominantly remained in the liver. Pretreatment with 20d5 appeared to facilitate disappearance of iNKT cells, particularly NK1(-) iNKT cells. Moreover, Con A-induced and alpha-galactosylceramide-induced hepatic injury was very severe in CD94/NKG2A-deficient DBA/2J mice compared with CD94/NKG2A-intact DBA/2JJcl mice. Overall, these results indicated that a NKG2A-mediated signal negatively regulates iNKT cell activation and hepatic injury.

Small cell carcinoma of the uterine cervix metastasizing to the bone marrow: a case report.

We report a case of small cell carcinoma (SmCC) of the uterine cervix that metastasized to the bone marrow. A 60-year-old woman with stage IIB SmCC of the cervix was treated with three courses of neoadjuvant chemotherapy followed by radical hysterectomy. Because of the presence of a large residual tumor, the patient underwent postoperative adjuvant chemotherapy. Two months after the last course of chemotherapy, severe pancytopenia developed, and erythroblastic cells were found in the peripheral blood. The hematological disorder was shown to be secondary to bone marrow metastasis, and no other metastases were found. The patient died of the disease 8 months after the initial diagnosis. This case suggests that SmCC of the cervix can metastasize to bone marrow, that such metastasis can occur in isolation and lead to severe pancytopenia, influencing the clinical course of the disease.

Human umbilical cord epithelial cells express Notch1: implications for its epidermal-like differentiation.

BACKGROUND: Notch1 receptor, a member of the Notch signaling pathway, is involved in the terminal differentiation process of epidermal keratinocytes. Human umbilical cord epithelia are continuous with embryonic and fetal epidermis during development, display cellular stratification and express differentiation markers related to the epidermis. As such, we hypothesized that Notch1 may be present in human umbilical cord epithelial cells (HUCEC). OBJECTIVE: To investigate the expression of Notch1 in HUCEC in vivo and in vitro. METHODS: Umbilical cord sections were probed with antibodies specific for Notch1, -2, -3, and -4. Expression of Notch transcripts in HUCEC in vitro was examined by RT-PCR analysis and protein expression was identified using immunocytochemistry and western blotting analysis. Using a three-dimensional organotypic culture system that promotes epidermal terminal differentiation, Notch1 expression was examined and changes in expression level were analysed using real-time quantitative PCR. RESULTS: Immunostaining of cord epithelia revealed expression of all four Notch receptors, with differential spatial distribution. Notch mRNA and protein were expressed in HUCEC in vitro. Specifically, western blotting revealed the presence of the transmembrane unit of the mature Notch1 heterodimeric receptor in HUCEC and epidermal keratinocytes. In organotypic culture, Notch1 mRNA was expressed in HUCEC with protein localised to the upper epithelial layers. Interestingly, Notch1 gene expression was down-regulated in HUCEC in organotypic culture compared to cells in submerged monolayer culture. CONCLUSION: HUCEC express Notch1 as in epidermal keratinocytes. The presence of Notch1 has implications for its involvement in the differentiation program of cord epithelia as a stratified epithelial tissue.

Expression of estrogen and progesterone receptors in smooth muscle metaplasia of rectovaginal endometriosis.

To investigate expression of estrogen receptors (ER) and progesterone receptors (PR) in smooth muscle metaplasia (SMM) outside the endometriotic foci of rectovaginal endometriosis (RVE). One hundred and ninety-five specimens were obtained from the rectovaginal areas of the 63 patients who were underwent laparoscopic surgery for RVE. The patients were divided into 3 groups: a gonadotropin-releasing hormone (GnRH) agonist group, a non-GnRH group, including a proliferative phase group, and a secretory phase group. Expression of ER and PR in the rectovaginal tissues of RVE were determined using immunohistochemical methods. Smooth muscle metaplasia occurred in 172 specimens (88.2%), and ER and PR expression were found in the smooth muscle cells in the SMM areas outside the endometriotic foci of RVE. The expression of ER and PR in the GnRH agonist group were significantly lower than those in the non-GnRH agonist group. This is the first report demonstrating ER and PR in the smooth muscle cells in SMM outside the endometriotic foci of RVE. The ER and PR were expressed in the SMM areas, but these receptors were not recognized in fibrotic areas. We could identify the expression ratio of these receptors during each menstrual phase, with or without administered GnRH agonist.

An inhibitory effect on cell proliferation by blockage of the MAPK/estrogen receptor/MDM2 signal pathway in gynecologic cancer.

OBJECTIVE: We previously demonstrated that that the Ras/ER/MDM2 pathway was critical for NIH3T3 cell transformation. In this study, we examined the effect of blocking this pathway on cell growth in gynecologic cancer cells. METHODS: (1) The levels of MDM2, ER, p53 and p21 in endometrial or ovarian cancer cell lines were investigated and compared with that in normal cells by Western blots. (2) The effects of MEK-inhibitor and/or anti-estrogen, and siRNA of MDM2 on cell growth, tumorigenicity in nude mice were examined. RESULTS: The MDM2 level was enhanced in cancer cells compared with normal cells. Treatment with MEK inhibitor(U0126) resulted in a reduced MDM2 level, enhanced p53 and p21 levels and inhibited cell growth by the induction of premature senescence. The effect of MEK inhibitor on cell growth was affected by ER levels and functions. Treatment with low-dose MEK inhibitor in combination with anti-estrogen (ICI182,780) had a more inhibitory effect on cell growth compared to treatment with MEK inhibitor or anti-estrogen alone in cancer cells. Down-regulation of the MDM2 level by siRNA resulted in the inhibition of growth in cancer cells. CONCLUSION: The blockage of the MAPK/ER/MDM2 pathway suppress cell proliferation and it is supposed as a new molecular target therapy in estrogen-dependent gynecologic cancers, such as endometrial or ovarian cancer.

Effectiveness of intraoperative ultrasound in reducing recurrent fibroids during laparoscopic myomectomy.

OBJECTIVE: To detect and study residual fibroids, their recurrence after laparoscopic myomectomy (LM) and the risk factors. STUDY DESIGN: A prospective analysis (Canadian Task Force classification II-1) was conducted at a university-affiliated hospital. A total of 42 patients who underwent LM underwent contact ultrasonography (CUS) and transvaginal ultrasonography (TVUS) to detect residual fibroids. After LM, additional enucleation guided by CUS was performed, and then the final residual fibroids were detected using TVUS. The frequency of postoperative residual fibroids and their characteristics were evaluated. All cases were followed for > 6 months postoperatively to assess recurrence. RESULTS: The total number of fibroids enucleated in the initial enucleation was 201, or 4.8 per patient. Median diameter of the largest fibroids for each patient was 60 mm. There were 25 additional fibroids enucleated with CUS guidance. Their median diameter was 12.1 mm. After the additional enucleation, 33 final residual fibroids were identified by TVUS. Their median diameter was 9.0 mm, which was significantly smaller than those of the additionally enucleated fibroids (p = 0.002). The frequency of patients with residual fibroids was calculated in relation to the number of enucleated fibroids. The results showed that the frequency tended to increase as the number of fibroids increased and that almost all the patients (7 of 8 cases, 87.5%) with > or = 10 fibroids had residual ones. The median follow-up period was 31 months (range, 6-37), and 8 cases (19.0%) had recurrent fibroids. The recurrence rate in patients with > or = 10 fibroids was 50%. CONCLUSION: Intraoperative CUS was useful in detecting and enucleating residualfibroids. As the number of enucleated fibroids increased, the risk of residual fibroids and recurrence tended to increase.

A novel instrument and technique for using Seprafilm hyaluronic acid/carboxymethylcellulose membrane during laparoscopic myomectomy.

Myomectomy is associated with the development of adhesions, and even when the patient is operated on laparoscopically, postoperative adhesions can often occur. Seprafilm is an effective and highly safe barrier to postoperative adhesions. However, it is vulnerable to tears and difficult to handle. We developed a device to introduce Seprafilm into the abdominal cavity during the laparoscopic procedure. Seprafilm is divided into 6 pieces and the pieces are rolled and inserted into the purpose-built introducer to be guided into the abdominal cavity. The inner syringe is pushed in and Seprafilm is applied onto the uterine wound with two grasping forceps. Of 117 patients in our study, we were able to use Seprafilm on 114 patients (97.4%). In total, 221 pieces of Seprafilm were used, and 87 pieces were damaged during the operation. Of these 87 pieces, 58 were damaged when inserted into the introducer, though this kind of loss tended to decrease with training, and 29 pieces were damaged during application to the wound. Seprafilm can be used safely and efficiently during laparoscopic surgery.

Recurrence rate of endometriomas following a laparoscopic cystectomy.

BACKGROUND: The objectives were to observe the clinical course of patients who underwent laparoscopic cystectomy (LC) using transvaginal ultrasonography. METHOD: The definition of "recurrence" was to detect a diffuse, hypoechoic area whose long axis was at least 2 centimeters (cm) on the transvaginal ultrasonogram during the postoperative follow-up period. Using the Cox regression test, we analyzed each patient's background variables, namely, patient's age, the revised American Society of Reproductive Medicine score (r-ASRM score), use of gonadotropin releasing hormone analogues (GnRHa), and pregnancy during the observation period. Next, cyst size and multi-lobularity of each of the 417 cysts were also analyzed as recurrence risk factors per cyst. RESULTS: The mean postoperative observation period was 21.4+/-16.8 months. During the observation period, 50 (15.9%) out of 315 patients experienced recurrence and 51 (16.2%) out of 315 patients became pregnant. The cumulative recurrence rate per patient was 31.7% over 60 months. Among prognostic factors per patient, age and showed negative and r-ASRM scores positive correlations with cyst recurrence. On the other hand, we did not identify any cyst factors associated with recurrence. The patients who underwent hemilateral LC showed a 5.2% cyst recurrence rate in the ovary that appeared to be normal at the time of the initial surgery. CONCLUSION: Young age and severe endometriosis appeared to be the factors associated with high recurrence risk. Recurring ovarian endometrimas probably include cysts occurring spontaneously and those recurring from the cyst residues in the lesions where cystectomy has been performed.

Histopathological study of the spreading neoplastic cells in cervical glands and surface epithelia in cervical intra-epithelial neoplasia and microinvasive squamous cell carcinoma: Ki-67 immunostaining is a useful marker for pathological diagnosis from the gland involvement site.

The purpose of the present study was to clarify the spreading status of neoplastic cells in the cervical glands and surface epithelia in cervical intra-epithelial neoplasia (CIN) and microinvasive squamous cell carcinoma (MiSCC), and to evaluate the diagnostic usefulness of Ki-67 immunostaining from the gland involvement (GI) site. Cervical conization samples from 120 patients, including 110 with CIN (CIN1, n=2; CIN2, n=21; CIN3, n=87) and 10 patients with MiSCC, was examined using HE and Ki-67 immunostaining. The linear extent, lateral extent in the surface epithelia and depth of GI were significantly increased from CIN1 to MiSCC. A significant correlation was found between the linear extent and lateral extent, between the linear extent and depth, and between the lateral extent and depth. These results indicated that the size of the surface epithelial lesion and the depth in CIN gradually increased in accordance with the grade of CIN, and that GI became deeper according to the increase in the size of the surface epithelial lesion. The Ki-67 labeling index in the GI site gradually increased from CIN1 to MiSCC, which indicated that Ki-67 immunostaining is a useful marker for the pathological diagnosis of CIN from the GI site.