Are HPV-negative lesions concerned for the introduction of primary HPV testing for cervical cancer screening in Japan?

AIM: In Japan, primary human papilloma virus (HPV) testing has not been introduced for cervical cancer screening due to concerns that HPV-negative lesions may be missed and a lack of Japanese data. The purpose of this study was to evaluate the validity of primary HPV testing in Japan by analyzing cervical intraepithelial neoplasia 2 (CIN2) or more/high-risk HPV- (CIN2+/hrHPV-) cases in cervical cancer screening. METHODS: Data from 35 525 cervical cancer screenings with HPV testing and cervical cytology from 2011 to 2019 in Saga City, Japan, were reviewed. The cases with low-grade squamous intraepithelial lesion (LSIL+)/hrHPV- were analyzed in detail. RESULTS: The results of the 35 525 examinees were as follows: 31 123 were negative for intraepithelial lesion or malignancy (NILM)/hrHPV-, 2612 were NILM/hrHPV+, 262 were atypical squamous cells of undetermined significance (ASC-US)/hrHPV-, 213 were ASC-US/hrHPV+, 291 were LSIL+/hrHPV-, and 1024 were LSIL+/hrHPV+. Of the 256 LSIL+/hrHPV- examinees for whom histology was available, CIN2+ were CIN2 9.4% (24/256), CIN3 3.9% (10/256), cervical adenocarcinoma 0.4% (1/256), uterine corpus cancer 1.2% (3/256), and uterine sarcoma 0.4% (1/256). Overall, the rate of LSIL+/hrHPV- was 0.82% (291/35.525), 0.1% (36/35525) of which were cervical lesions with CIN2+. Only one cervical adenocarcinoma was detected, but gastric-type adenocarcinoma was not included. CONCLUSION: HPV-negative CIN2+ or cervical adenocarcinoma is not a concern for the introduction of primary HPV screening in Japan. Primary HPV testing in cervical cancer screening is considered a feasible method that can be used in Japan, although an algorithm suitable for Japan and a national-level management system need to be established.

Fetal sex and maternal insulin resistance during mid-pregnancy: a retrospective cohort study.

BACKGROUND: Recent studies have suggested that fetal sex influences maternal glucose and insulin metabolism during pregnancy. We examined whether fetal sex is associated with maternal insulin resistance and the ß-cell function during mid-pregnancy. METHODS: This retrospective study included singleton pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) at 24-34 weeks of gestation due to positive diabetic screening. In addition to plasma glucose (PG), we measured plasma insulin during the OGTT to obtain surrogate indices associated with insulin resistance (IR), including homeostasis assessment model (HOMA) -IR and insulin sensitivity index (IsOGTT), and ß-cell function, including insulinogenic index (II), HOMA-ß, and area under the curve of insulin response. We compared these indices between women carrying male fetuses to those carrying female fetuses. RESULTS: The study population included 617 women (mean age, 32.4 ± 4.9 years) with a mean pre-pregnancy body mass index (BMI) of 22.6±4.5. They underwent the 75g-OGTT at 29.0 ± 2.5 weeks. Two hundred fifty-eight (42%) women were diagnosed with gestational diabetes (GDM). There was no significant difference in maternal age, pre-pregnancy BMI, gestational age at OGTT, PG at OGTT, or the prevalence of GDM between women with a male fetus (n=338) (male group) and those with a female fetus (n=279) (female group). Regarding the indices of IR, IR was significantly higher and insulin sensitivity was lower in the female group than in the male group (HOMA-IR: 7.0 [5-9.6] vs. 6.2 [4.6-8.8], p< 0.05; IsOGTT: 5.86 [4.29-7.83] vs. 6.29 [4.59-8.84], p< 0.01) (median [quartile range]). These differences remained significant after adjustment for maternal age, pre-pregnancy BMI, gestational age and fasting PG at OGTT, and the diagnosis of GDM. In contrast, the ß-cell function did not differ between the two groups. CONCLUSION: Maternal IR during mid-pregnancy was significantly higher in women carrying a female fetus than in those with a male fetus. The sex of the fetus may affect maternal insulin sensitivity during mid-pregnancy.

Risk factors associated with the development of postpartum diabetes in Japanese women with gestational diabetes.

BACKGROUND: Although the onset of gestational diabetes (GDM) is known to be a significant risk factor for the future development of type 2 diabetes, this risk specifically in women with GDM diagnosed by the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria has not yet been thoroughly investigated. This study was performed to investigate the risk factors associated with the development of postpartum diabetes in Japanese women with a history of GDM, and the effects of the differences in the previous Japanese criteria and the IADPSG criteria. METHODS: This retrospective cohort study included Japanese women with GDM who underwent at least one postpartum oral glucose tolerance test (OGTT) between 2003 and 2014. Cases with overt diabetes in pregnancy were excluded. We investigated the risk factors including maternal baseline and pregnancy characteristics associated with the development of postpartum diabetes. RESULTS: Among 354 women diagnosed with GDM during the study period, 306 (86%) (116/136 [85.3%] and 190/218 [87.2%] under the previous criteria and the IADPSG criteria, respectively) who underwent at least 1 follow-up OGTT were included in the study. Thirty-two women (10.1%) developed diabetes within a median follow-up period of 57 weeks (range, 6-292 weeks). Eleven (9.5%) and 21 (11.1%) were diagnosed as GDM during pregnancy based on the previous Japanese criteria and the IADPSG criteria, respectively, which did not significantly differ between those criteria. A multivariate logistic regression analysis revealed that HbA1c and 2-h plasma glucose (PG) at the time of the diagnostic OGTT during pregnancy were independent predictors of the development of diabetes after adjusting for confounders. The adjusted relative risk of HbA1c ≥5.6% for the development of diabetes was 4.67 (95% confidence interval, 1.53-16.73), while that of 2-h PG ≥183 mg/dl was 7.02 (2.51-20.72). CONCLUSIONS: A modest elevation of the HbA1c and 2-h PG values at the time of the diagnosis of GDM during pregnancy are independent predictors of the development of diabetes during the postpartum period in Japanese women with a history of GDM. The diagnostic criteria did not affect the incidence of postpartum diabetes.

Factors associated with patients with gestational diabetes in Japan being at increased risk of requiring intensive care.

OBJECTIVE: To investigate factors associated with high-risk gestational diabetes (GDM) among patients with GDM. METHODS: The present retrospective study included women with singleton pregnancies diagnosed with GDM using International Association of Diabetes and Pregnancy Study Group criteria at a single tertiary perinatal care center in Japan between July 1, 2010, and October 31, 2014. High-risk GDM was defined as patients who required at least 20 units of insulin therapy a day, delivering a large-for-gestational age neonate regardless of insulin therapy, or both. Maternal characteristics and diagnostic test results were investigated to identify associations with the high-risk criteria, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Among 217 patients, 95 (43.8%) were categorized as high risk. After adjusting for confounders, a fasting plasma glucose level at diagnosis of at least 4.66 mmol/L (adjusted OR 2.88, 95% CI 1.51-5.58) and pre-pregnancy body mass index (calculated as weight in kilograms divided by the square of height in meters) of at least 24 (adjusted OR 3.27, 95% CI 1.60-6.90) were independently associated with meeting the high-risk criteria. CONCLUSION: Among Japanese patients with GDM, pre-pregnancy body mass index and fasting plasma glucose levels could be used to identify high-risk patients requiring intensive care during pregnancy.

The effect of high-intensity breastfeeding on postpartum glucose tolerance in women with recent gestational diabetes.

BACKGROUND: Although breastfeeding is expected to reduce the incidence of diabetes in women with gestational diabetes, the effect has not been clearly confirmed. We examined whether or not high-intensity breastfeeding reduces the incidence of abnormal glucose tolerance and investigated the effect of high-intensity breastfeeding on insulin resistance during the first year postpartum in Japanese women with current gestational diabetes. METHODS: In this retrospective study, we included women with gestational diabetes who underwent postpartum 75 g oral glucose tolerance test during the first year (12-14 months) postpartum from 2009 to 2011 at a single tertiary perinatal care center in Japan. High-intensity breastfeeding was defined as the condition in which infants were fed by breastfeeding alone or 80% or more of the volume. We investigated the effect of high-intensity breastfeeding on the prevalence of postpartum abnormal glucose tolerance and the postpartum homeostasis model of assessment of insulin resistance (HOMA-IR), after controlling for confounders, including prepregnancy obesity and weight changes during pregnancy and postpartum. RESULTS: Among 88 women with gestational diabetes, 46 (52%) had abnormal glucose tolerance during the postpartum period. High-intensity breastfeeding women (n = 70) were significantly less likely to have abnormal glucose tolerance than non-high-intensity breastfeeding women (n = 18) (46% vs. 78%, p = 0.015). High-intensity breastfeeding was also associated with a lower HOMA-IR at 12-14 months postpartum than non-high-intensity breastfeeding (1.41 ± 1.02 vs. 2.28 ± 1.05, p = 0.035). Those associations remained significant after controlling for confounders. At least six months of high-intensity breastfeeding had a significant effect on lowering both the abnormal glucose tolerance prevalence and HOMA-IR compared with non-high-intensity breastfeeding. CONCLUSIONS: In Japanese women with gestational diabetes, high-intensity breastfeeding ≥6 months had a protective effect against the development of abnormal glucose tolerance during the first year postpartum through improving insulin resistance, independent of obesity and postpartum weight change.

Influence of the interval between antenatal corticosteroid therapy and delivery on respiratory distress syndrome.

AIM: In spite of the recommendation for rescue antenatal corticosteroids (ACS), the optimal time interval between primary and rescue courses has not been clearly demonstrated. The aim of this study was to determine the effects of the interval between a single ACS course and delivery on the incidence of respiratory distress syndrome (RDS). METHODS: In this retrospective study, we included singleton pregnant women who received a single course of ACS and delivered beyond 48 h after ACS administration between 24 and 33 weeks' gestation. The risk of RDS was compared between patients who delivered within seven days (Group I), 7-14 days (Group II) and beyond 14 days (Group III) after ACS administration. RESULTS: We included 83, 14 and 20 patients in Groups I, II and III, respectively. After adjusting for confounders, the ACS delivery interval was significantly associated with RDS in Group II (adjusted odds ratio 12.8, 95% confidence interval 1.31-164.7) and Group III (adjusted odds ratio 64.0, 95% confidence interval 1.32-5808.6). CONCLUSION: A longer ACS delivery interval is associated with a higher risk of RDS. Thus, the use of a rescue course could be expected to reduce the incidence of RDS in patients beyond seven days after ACS administration who remain at risk for preterm delivery within seven days, especially in cases of placenta previa and/or women bearing a male fetus.

Low Expression of S100P Is Associated With Poor Prognosis in Patients With Clear Cell Adenocarcinoma of the Ovary.

OBJECTIVE: The S100P protein stimulates cell proliferation and survival, thereby contributing to cancer progression. The purposes of this study were to evaluate S100P expression in ovarian clear cell adenocarcinoma and to determine whether S100P expression was correlated with the clinicopathological features or prognoses of patients with clear cell adenocarcinoma. METHODS: We examined S100P expression in 30 ovarian clear cell adenocarcinoma specimens using immunohistochemistry analysis. The Kaplan-Meier method was used for analysis of overall survival, and comparisons were made based on the log-rank test. RESULTS: Negative staining for nuclear S100P was associated with a poor prognosis as compared with that of positive staining for nuclear S100P in specimens from patients with clear cell adenocarcinoma. CONCLUSIONS: These data suggested that S100P may serve as an independent prognostic factor and marker for acquired resistance to chemotherapeutic drugs in clear cell adenocarcinoma.

Risk factors associated with abnormal glucose tolerance in the early postpartum period among Japanese women with gestational diabetes.

OBJECTIVE: To identify the risk factors associated with abnormal glucose tolerance (AGT) on the first postpartum oral glucose tolerance test (OGTT) among Japanese women with gestational diabetes (GDM). METHODS: In a retrospective study, data were analyzed from women with GDM who underwent their first postpartum OGTT 6-8weeks post partum at a center in Omura, Japan, between January 1, 2007, and December 31, 2011. Women with diabetes or impaired glucose tolerance were deemed to have postpartum AGT. The association between postpartum AGT and various risk factors was analyzed. RESULTS: Among 169 women who underwent a postpartum OGTT, 58 (34.3%) had AGT. The significant risk factors associated with postpartum AGT in univariate analysis were pre-pregnancy body mass index (P=0.096), 1-hour plasma glucose (P=0.006), hemoglobin A1c (P<0.001), insulinogenic index (P=0.05), an insulinogenic index of less than 0.4 (P=0.006), and insulin therapy during pregnancy (P<0.001). Independent risk factors identified by multivariate logistic regression models were insulinogenic index (odds ratio [OR] 0.10, 95% confidence interval [CI] 0.01-0.74; P=0.002), an insulinogenic index of less than 0.4 (OR 5.70, 95% CI 1.69-21.66; P=0.005), and insulin therapy during pregnancy (OR 3.43, 95% CI 1.03-12.55; P=0.044). CONCLUSION: Among Japanese women with GDM, a lower insulinogenic index and use of insulin therapy during pregnancy are associated with early postpartum AGT.

The association between maternal insulin resistance in mid-pregnancy and neonatal birthweight in uncomplicated pregnancies.

There have been few studies performed to address the association between the degree of physiological increase in maternal insulin resistance during pregnancy and neonatal birthweight in non-diabetic pregnancy. We attempted to determine whether maternal insulin resistance, as measured by homeostasis model assessment-insulin resistance (HOMA-IR), in mid-pregnancy is associated with neonatal birthweight in normal pregnancies. In this retrospective observational study, we measured HOMA-IR in singleton healthy pregnant women who underwent a 75 g oral glucose tolerance test (OGTT) in mid-pregnancy because of a positive diabetes screen. Using multivariate analyses to adjust for maternal parity, pre-gestational obesity, gestational weight gain, plasma glucose levels, and gestational age at delivery, we tested the association between HOMA-IR and birthweight in their offspring. We also tested the association HOMA-IR and a risk of large-for-gestational-age (LGA) infants. In 655 Japanese women, HOMA-IR was positively associated with birthweight after adjusting for these confounders (p<0.05). A higher HOMA-IR was significantly associated with an increased incidence of LGA infants with an adjusted odds ratio of 1.53 (95% confidence interval, 1.10-2.15) per 1 unit of HOMA-IR. The degree of maternal insulin resistance in mid-pregnancy was associated with birthweight and the risk of giving birth to an LGA infant in normal pregnancies, independent of maternal obesity and glucose levels.