Clinical impact of age­specific distribution of combination patterns of cytology and high­risk HPV status on cervical intraepithelial neoplasia grade 2 or more.

To the best of our knowledge, the present study is the first to elucidate the significance of cytology and high-risk human papillomavirus (hrHPV) status in different age groups for the detection of cervical intraepithelial neoplasia (CIN)2, CIN3 and squamous cell carcinoma (SCC). There were 12 combinations based on cytology and hrHPV status [cytology: Atypical squamous cells (ASC) of undetermined significance, low-grade squamous intraepithelial lesion, ASC not excluding high-grade squamous intraepithelial lesion (HSIL) and HSIL; hrHPV status: HPV16/18-positive (16/18+), hrHPV positive for subtypes other than 16/18 (others+) and hrHPV-negative (hrHPV-)]. All patients were categorized into four groups based on age (18-29, 30-39, 40-49 and ≥50 years). For patients with CIN2, CIN3 and SCC (CIN2+) (n=107), the distribution of cytology and hrHPV was investigated in each age group. In addition, for all patients (n=446), the occurrence of CIN2+ in each of the 12 combinations was investigated in each age group. In the 18-29-year age group, the most common combination was HSIL and 16/18+, followed by HSIL and others+, which accounted for 73% of CIN2+ cases. The occurrence of HSIL and 16/18+ decreased with increasing age, and no cases occurred in the 50-year age group. In the 18-29-year age group, all patients with HSIL and 16/18+ were diagnosed with CIN2+. CIN2+ was predominantly detected in patients with HSIL in the 18-29-year age group, as well as hrHPV- and others+. This definite distinction was not observed in any other age group. For CIN2+, the distribution patterns of cytology and hrHPV status combinations varied significantly among different age groups. Accordingly, the clinical impact of the combination of cytological findings and hrHPV status can vary among age groups.

Full-term low birth weight infants have differentially hypermethylated DNA related to immune system and organ growth: a comparison with full-term normal birth weight infants.

OBJECTIVE: Low birth weight (LBW) is a major public health issue as it increases the risk of noncommunicable diseases throughout life. However, the genome-wide DNA methylation patterns of full-term LBW infants (FT-LBWs) are still unclear. This exploratory study aimed to analyze the DNA methylation differences in FT-LBWs compared with those in full-term normal birth weight infants (FT-NBWs) whose mothers were nonsmokers and had no complications. Initially, 702 Japanese women with singleton pregnancies were recruited. Of these, four FT-LBWs and five FT-NBWs were selected as references for DNA methylation analysis, and 862,260 CpGs were assessed using Illumina Infinium MethylationEPIC BeadChip. Gene ontology enrichment analysis was performed using DAVID v6.8 software to identify the biological functions of hyper- and hypomethylated DNA in FT-LBWs. RESULTS: 483 hyper-differentially methylated genes (DMGs) and 35 hypo-DMGs were identified in FT-LBW promoter regions. Hyper-DMGs were annotated to 11 biological processes; "macrophage differentiation" (e.g., CASP8), "apoptotic mitochondrial changes" (e.g., BH3), "nucleotide-excision repair" (e.g., HUS1), and "negative regulation of inflammatory response" (e.g., NLRP12 and SHARPIN). EREG was classified into "ovarian cumulus expansion" within the "organism growth and organization" category. Our data imply that LBW might be associated with epigenetic modifications, which regulate the immune system and cell maturation.

Association between socioeconomic status and small-for-gestational-age in Japan: A single center retrospective cohort study.

AIM: Small-for-gestational-age (SGA) status has negative health consequences in neonates and later life. Low socioeconomic status (SES) is a reported risk factor for adverse birth outcomes, such as SGA and preterm birth (PTB). The present study investigated whether maternal SES is associated with adverse outcomes in Japanese pregnant women. METHODS: Retrospective data were collected for 1970 Japanese women with singleton pregnancies who delivered between January 2007 and December 2011 at a single center: low SES group (n = 197); and controls (n = 1773). Low SES was defined according to the criteria of the Japanese pregnant-childbirth hospitalization support policy system. RESULTS: The low SES group included a significantly higher proportion of young women, women with single marital status, greater parity, pre-pregnancy smoking and a lack of regular employment (P < 0.001, respectively). The crude odds ratio (OR) for the association between low maternal SES and SGA was 1.80 (95% confidence interval [CI] 1.15-2.82, P = 0.010). After adjustment for baseline maternal age, parity, body mass index, smoking and gestational weight gain, the adjusted OR for the association between low maternal SES and SGA was 1.92 (95% CI 1.17-3.17, P = 0.010). No significant association was found between maternal SES and PTB. CONCLUSION: The present results suggest that low maternal SES is associated with SGA births in the Japanese population. Mitigation of low maternal SES could be urgent public health to prevent disadvantage birth outcome.

Detection of tumor cells of serous tubal intraepithelial carcinoma (STIC) in cervical smears and rapid development of the ovarian involvement: A case report.

Serous tubal intraepithelial carcinoma (STIC) has attracted attention as a precursor lesion of high-grade serous carcinoma (HGSC) of the ovary. We report the rare case of a woman in whom adenocarcinoma cells were detected in cervical smears and demonstrated to be derived from STIC in the fimbria. The patient was a 48-year-old woman, in whom cervical smears contained adenocarcinoma cells, but cervical conization did not reveal adenocarcinoma. Because the post-conization smears again demonstrated adenocarcinoma cells, hysterectomy with bilateral salpingectomy was performed 16 months after the first detection of adenocarcinoma cells in cervical smears. Histopathological examination demonstrated STIC in the fimbria of the left fallopian tube. Bilateral ovaries appeared grossly normal at that time, but oophorectomy, which was performed 3 months later, disclosed HGSC involving the surface of bilateral ovaries. Detection of carcinoma cells from STIC in cervical smears is of marked significance for the management of patients, and we should keep in mind the possibility that adenocarcinoma cells in cervical smears are derived from STIC. The postoperative outcome of patients with STIC is considered generally favorable, and the clinical course of the present patient, in whom HGSC involving the bilateral ovaries was found shortly after salpingectomy, is exceptional.

Chemosensitivity testing of paclitaxel versus docetaxel in human gynecological carcinomas: a comparison with carboplatin.

BACKGROUND: The tetrazolium dye (MTT) assay is useful in predicting chemosensitivity. MATERIALS AND METHODS: Using the MTT assay, an in vitro chemosensitivity test was designed for paclitaxel and docetaxel. The results were then compared with the sensitivity to carboplatin in 60 resected gynecological carcinomas. RESULTS: The mean tumor inhibition rates [I.R.s; %] for paclitaxel, docetaxel and carboplatin were all higher in ovarian carcinomas than in endometrial carcinomas [74.3% vs. 47.3% (p < 0.01), 57.2% vs. 21.9% (p < 0.001), 71.3% vs. 50.1% (p < 0.01), respectively]. In 28 ovarian carcinomas, the I.R.s for paclitaxel and carboplatin were higher than docetaxel [74.3% and 71.3% vs. 57.2%, respectively (p < 0.05)]. In particular, the I.R. for paclitaxel was significantly higher than docetaxel [83.0% vs. 62.9% (p < 0.05)] in serous adenocarcinomas. In clear cell adenocarcinomas, however, both the I.R.s for paclitaxel and docetaxel were significantly lower than carboplatin [27.8% and 23.3% vs. 58.5%, respectively (p < 0.01)]. In 10 cervical carcinomas, the I.R. for docetaxel was significantly lower than paclitaxel and carboplatin [39.5% vs. 64.1% and 60.5%, respectively (p < 0.05)]. In 22 endometrial carcinomas, the I.R. for docetaxel was also lower than paclitaxel and carboplatin [21.9% vs. 47.4% and 50.1% (p < 0.01, p < 0.001, respectively)]. Furthermore, the I.R. for docetaxel was significantly lower in G2 and G3 adenocarcinomas [16.9% vs. 45.8% and 52.8% (p < 0.05, p < 0.01, respectively)] [16.5% vs. 46.2% and 53.2% (p < 0.01, p < 0.001, respectively)]. CONCLUSION: The antitumor activity of both paclitaxel and docetaxel was higher in ovarian carcinomas than in endometrial carcinomas. In ovarian carcinomas, however, paclitaxel and carboplatin were superior to docetaxel. In cervical and endometrial carcinomas, docetaxel was significantly worse than paclitaxel and carboplatin.

Chemosensitivity testing of a novel platinum analog, nedaplatin (254-S), in human gynecological carcinomas: a comparison with cisplatin.

BACKGROUND: The tetrazolium dye (MTT) assay is useful for predicting chemosensitivity. MATERIALS AND METHODS: Using the MTT assay, an in vitro chemosensitivity test was designed for nedaplatin (cis-diammine glycolato platinum; 254-S) and the results were compared with the sensitivity to cisplatin in 137 resected gynecological carcinomas. RESULTS: The mean tumor inhibition rate [I.R.; %] for nedaplatin was equal or superior to cisplatin in 15 cervical [70.7% vs. 63.9%], 65 ovarian [61.7% vs. 54.8%] and 57 endometrial carcinomas [52.1% vs. 47.7%]. In ovarian carcinomas, the I.R.s for nedaplatin were significantly higher than cisplatin in poorly-differentiated, serous and endometrioid adenocarcinomas 180.7% vs. 56.4% (p < 0.05), 77.0% vs. 64.9% (p < 0.01), and 68.2% vs. 54.6% (p < 0.05), respectively]. CONCLUSION: Our data suggest that nedaplatin has equivalent or superior antitumor activity to cisplatin in cervical, ovarian and endometrial carcinomas. In particular, nedaplatin showed a significantly better antitumor activity among the histological subtypes of ovarian carcinomas.