Assessment of the localization of chondroitin sulfate in various types of endometrial carcinoma.

INTRODUCTION: This study aimed to assess the localization of chondroitin sulfate (CS), a primary extracellular matrix component, in the stromal region of endometrial carcinoma (EC). METHODS: Immunostaining was performed on 26 endometrial endometrioid carcinoma (EEC) samples of different grades and 10 endometrial serous carcinoma (ESC) samples to evaluate CS localization. This was further confirmed by Alcian Blue (AB) staining as well. RESULTS: In the G1-EEC samples, CS showed reactivity with fibrovascular stroma, supporting closely packed glandular crowding and papillary structures. As the grade increased, the original interstitial structure was re-established, and the localization of CS in the perigulandular region decreased. In the ESC samples, the thick fibrous strands supporting the papillary architecture showed reactivity with CS; however, the delicate stromal region branching into the narrow region showed poor reactivity. The AB staining results showed similar characteristics to the immunostaining ones. CONCLUSIONS: The characteristic localization of CS in various EC types was elucidated. The present study provides new information on endometrial stromal assessment.

Establishment of a human ovarian clear cell carcinoma cell line mutant in PIK3CB but not PIK3CA.

A human ovarian clear cell carcinoma cell line was established from a 46-year-old Japanese woman. That line, designated MTC-22, has proliferated continuously for over 6 months in conventional RPMI 1640 medium supplemented with 10% foetal bovine serum and has been passaged over 50 times. MTC-22 doubling-time is ~ 18 h, which is much shorter than most ovarian clear cell carcinoma lines reported to date. Morphologically, MTC-22 cells exhibit polygonal shapes and proliferate to form a monolayer in a jigsaw puzzle-like arrangement without contact inhibition. Ultrastructurally, cells exhibit numerous intracytoplasmic glycogen granules and well-developed mitochondria. G-band karyotype analysis indicated that cells have a complex karyotype close to tetraploid. We observed that the expression pattern of a series of ovarian carcinoma-related molecules in MTC-22 cells was identical to that seen in the patient's tumour tissue. Notably, MTC-22 cells, and the patient's carcinoma tissue, expressed low-sulphated keratan sulphate recognised by R-10G and 294-1B1 monoclonal antibodies, a hallmark of non-mucinous ovarian carcinoma, and particularly of clear cell ovarian carcinoma. Moreover, characteristic point mutations-one in ARID1A, which encodes the AT-rich interaction domain containing protein 1A, and the other in PIK3CB, which encodes the catalytic subunit of phosphoinositide 3-kinase-were seen in the patient's tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring PIK3CB mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.

Structural Elucidation and Prognostic Relevance of 297-11A-Sulfated Glycans in Ovarian Carcinoma.

Ovarian carcinoma is usually diagnosed at an advanced stage with peritoneal dissemination and/or lymph node metastasis, and the prognosis for such advanced carcinoma is very poor. Therefore, new biomarkers to predict patient prognosis are needed. Miyamoto et al. previously showed that keratan sulfate (KS) detected by the 5D4 monoclonal antibody was expressed in ovarian carcinoma. However, the detailed structure of such KS was not determined, and the biological significance of this finding remained to be clarified. We previously generated the 297-11A monoclonal antibody, which recognizes galactose (Gal)-6-O-sulfated N-acetyllactosamine (LacNAc) located at the nonreducing terminus. Because the 297-11A epitope overlaps with that of 5D4, here we chose to use the 297-11A antibody as a tool to analyze KS and related structures. We conducted immunohistochemical analysis of 98 ovarian carcinoma cases with 297-11A antibody combined with a series of glycosidases and performed mass spectrometry analysis of the human serous ovarian carcinoma cell line OVCAR-3 to deduce the glycan structure of 297-11A-sulfated glycans. We also performed western blot analysis to assess a potential association of 297-11A-sulfated glycans with the mucin core protein mucin 16 (MUC16; also known as cancer antigen 125 (CA125)). Finally, we examined the relationship between 297-11A expression and patient prognosis. Consequently, 297-11A-sulfated glycans were primarily expressed in serous and endometrioid carcinomas and poorly expressed in mucinous and clear cell carcinomas. We reveal that structurally, 297-11A-sulfated glycans expressed in ovarian carcinoma are O-glycans carrying partially sialylated, Gal-6-O-sulfated LacNAc and that these glycans are likely displayed on MUC16 mucin core proteins. Of clinical importance is that expression of 297-11A-sulfated glycans correlated with shorter progression-free survival in patients. Thus, 297-11A-sulfated glycans may serve as a predictor of ovarian carcinoma recurrence.

Evaluating Opt-In Vaginal Human Papillomavirus Self-Sampling: Participation Rates and Detection of High-Grade Lesions (CIN2+) among Unscreened Japanese Women Aged 30-39.

Cervical cancer incidence is increasing among Japanese women, which is partly attributed to low screening rates. This study examined the implementation of opt-in human papillomavirus (HPV) self-sampling among Japanese women aged 30-39 years who had not undergone cervical cancer screening, focusing on those requiring preconception care. The responses to the opt-in approach and effectiveness in detecting cervical squamous intraepithelial neoplasia 2 or worse (CIN2+) were evaluated. Participants used the Evalyn® Brush for self-sampling, with HPV testing conducted using the Cobas 4800 system (version 2.2.0). Out of 3489 eligible, unscreened women from four municipalities in Fukui Prefecture, only 10.6% (370/3489) requested the self-sampling kit. Of these, 77.3% (286/370) returned the kit (HPV testing rate: 8.2% (286/3489)). The HPV positivity rate was 13.7% (39/285), yet only 61.5% (24/39) of those with positive HPV results proceeded to cytology testing. Subsequently, three cases of CIN2+ were detected (10.5/1000). While this study demonstrated a reasonable kit return rate and indicated the capability of opt-in HPV self-sampling to detect CIN2+ cases in unscreened women, the low ordering rate of kits and suboptimal compliance for follow-up cytology testing highlight significant challenges. The findings suggest the need for more effective strategies to enhance participation in cervical cancer screening programs.

Hidden in plain sight - Survival consequences of baseline symptom burden in women with recurrent ovarian cancer.

OBJECTIVE: To describe the baseline symptom burden(SB) experienced by patients(pts) with recurrent ovarian cancer(ROC) prior and associations with progression free survival (PFS) and overall survival (OS). METHODS: We analysed baseline SB reported by pts. with platinum resistant/refractory ROC (PRR-ROC) or potentially­platinum sensitive ROC receiving their third or greater line of chemotherapy (PPS-ROC≥3) enrolled in the Gynecologic Cancer InterGroup - Symptom Benefit Study (GCIG-SBS) using the Measure of Ovarian Symptoms and Treatment concerns (MOST). The severity of baseline symptoms was correlated with PFS and OS. RESULTS: The 948 pts. reported substantial baseline SB. Almost 80% reported mild to severe pain, and 75% abdominal symptoms. Shortness of breath was reported by 60% and 90% reported fatigue. About 50% reported moderate to severe anxiety, and 35% moderate to severe depression. Most (89%) reported 1 or more symptoms as moderate or severe, 59% scored 6 or more symptoms moderate or severe, and 46% scored 9 or more symptoms as moderate or severe. Higher SB was associated with significantly shortened PFS and OS; five symptoms had OS hazard ratios larger than 2 for both moderate and severe symptom cut-offs (trouble eating, vomiting, indigestion, loss of appetite, and nausea; p < 0.001). CONCLUSION: Pts with ROC reported high SB prior to starting palliative chemotherapy, similar among PRR-ROC and PPS-ROC≥3. High SB was strongly associated with early progression and death. SB should be actively managed and used to stratify patients in clinical trials. Clinical trials should measure and report symptom burden and the impact of treatment on symptom control.

Evaluation of the holding-up uterus technique for placenta accreta spectrum cesarean hysterectomy in shocked patients with a high shock index: a case series study.

BACKGROUND: Placenta accreta spectrum (PAS) cesarean hysterectomy is performed under conditions of shock and can result in serious complications. This study aimed to evaluate the usefulness of the "Holding-up uterus" surgical technique with a shock index (S.I.) > 1.5. METHODS: Twelve patients who underwent PAS cesarean hysterectomy were included in the study. RESULTS: Group I had S.I. > 1.5, and group II had S.I. ≤ 1.5. Group I had more complications, but none were above Grade 3 or fatal. Preoperative scheduled uterine artery embolization did not result in serious complications, but three patients who had emergency common iliac artery balloon occlusion (CIABO) and a primary total hysterectomy with S.I. > 1.5 had postoperative Grade 2 thrombosis. Two patients underwent manual ablation of the placenta under CIABO to preserve the uterus, both with S.I. > 1.5. CONCLUSIONS: The study found that the "Holding-up uterus" technique was safe, even in critical situations with S.I. > 1.5. CIABO had no intervention effect. The study also identified assisted reproductive technology pregnancies with a uterine cavity length of less than 5 cm before conception as a critical factor.

Expression of low-sulfated keratan sulfate in non-mucinous ovarian carcinoma.

Keratan sulfate glycosaminoglycan is composed of repeating N-acetyllactosamine (LacNAc) disaccharide units consisting of galactose (Gal) and N-acetylglucosamine (GlcNAc), both often 6-O-sulfated. Sulfate contents of keratan sulfate are heterogeneous depending upon the origins. In this study, keratan sulfate is classified as either highly sulfated (in which both GlcNAc and Gal residues are 6-O-sulfated) or low-sulfated (in which only GlcNAc residues are 6-O-sulfated). It is reported that highly sulfated keratan sulfate detected by the 5D4 monoclonal antibody is preferentially expressed in normal epithelial cells lining the female genital tract and in their neoplastic counterparts; however, expression of low-sulfated keratan sulfate in either has not been characterized. In the present study, we generated the 294-1B1 monoclonal antibody, which selectively recognizes low-sulfated keratan sulfate, and performed precise glycan analysis of sulfated glycans expressed on human serous ovarian carcinoma OVCAR-3 cells. We found that OVCAR-3 cells do not express highly sulfated keratan sulfate but rather express low-sulfated form, which was heterogeneous in 294-1B1 reactivity. Comparison of mass spectrometry spectra of sulfated glycans in 294-1B1-positive versus -negative OVCAR-3 cells indicated that the 294-1B1 epitope is likely at least 2, and possibly 3 or more, tandem GlcNAc-6-O-sulfated LacNAc units. Then, using the 294-1B1 antibody, we performed quantitative immunohistochemical analysis of 40 specimens from patients with ovarian cancer, consisting of 10 each of serous, endometrioid, clear cell, and mucinous carcinomas, and found that among them low-sulfated keratan sulfate was widely expressed in all but mucinous ovarian carcinoma.

Rectus Sheath Hematoma Triggered by Post-cesarean Anticoagulant Therapy for Intraoperative Acute Pulmonary Thromboembolism: A Case Report.

Anticoagulant therapy is essential for the prevention or treatment of peripartum venous thromboembolism (VTE). Administration of a therapeutic dose of anticoagulant immediately after cesarean section may result in the formation of a rectus sheath hematoma. A 32-year-old Japanese woman delivered twin neonates by cesarean section at 37+5 weeks of gestation. After the removal of the placenta, the patient suddenly complained of left anterior chest pain and dyspnea with hypotension and desaturation, requiring the administration of oxygen and vasopressors. Postoperative contrast-enhanced computed tomography (CT) revealed pulmonary embolism and massive right ovarian vein thrombosis (OVT). An inferior vena cava filter was placed and continuous intravenous heparin was started. A rectus sheath hematoma was noted on postoperative day 2 (POD 2). On POD 5, heparin administration was temporarily discontinued because of an enlarged rectus sheath hematoma. Approximately 24 hours later, the hemoglobin level recovered, and heparin administration was resumed. No further expansion of the hematoma was observed. When a rectus sheath hematoma is formed due to treatment with a therapeutic dose of anticoagulant immediately after cesarean section for peripartum VTE, temporary suspension of anticoagulant administration is reasonable to prevent further expansion of the hematoma without fatal complication.

Prognostic value of 18F-FDG PET in uterine cervical cancer patients with stage IIICr allocated by imaging.

The effect on survival of radiographic lymph node metastasis in uterine cervical cancer patients is more important than before, even though its prognostic value not been well investigated. The aim of our study is to evaluate the prognostic potential of 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) compared with Computed Tomography (CT) in uterine cervical cancer patients with stage IIICr allocated by imaging. Fifty-five patients with biopsy-proven primary cervical cancer underwent definitive radiation therapy for stages IIB-IVB of The International Federation of Gynecology and Obstetrics (FIGO) 2018 classifications. The prognostic performance of pretreatment 18F-FDG PET and CT for assessing lymph node metastasis was evaluated by two experienced readers. The PET and CT findings were correlated with the risk of progression-free survival (PFS) and overall survival (OS). Kaplan-Meier survival curves showed that PFS was significantly worse in patients with positive lymph nodes on 18F-FDG PET than in those patients with negative lymph nodes on 18F-FDG PET (p = 0.003), whereas there was no significant difference in PFS between patients with lymph nodes sized ≥ 1 cm and those sized < 1 cm (p = 0.140). Univariate analysis showed that positive lymph nodes on 18F-FDG PET was significantly associated with poor PFS (p = 0.006), whereas lymph node size was not significantly associated with poor PFS (p = 0.145). In multivariate analysis, positive lymph nodes on 18F-FDG PET was significantly associated with poor PFS (p = 0.006) and was an independent prognostic factor for PFS. 18F-FDG PET offers high prognostic value for patients with stage IIICr allocated by imaging compared with CT, suggesting that 18F-FDG PET might be useful in clinical staging decisions and thus promote optimal diagnostic and therapeutic strategies.

Longitudinal changes in attention bias to infant crying in primiparous mothers.

Introduction: Infant stimuli attract caregiver attention and motivate parenting behavior. Studies have confirmed the existence of attentional bias toward infant face stimuli; however, relatively little is known about whether attentional bias exists for infant cry stimuli, which are as important as faces in child-rearing situations. Furthermore, scarce longitudinal evidence exists on how attentional bias toward infant crying changes through the postpartum period. Methods: In the present study, we conducted an experiment to assess bias toward infant crying at two postpartum time points: at Time 1 (Mean = 75.24 days), 45 first-time mothers participated and at Time 2 (Mean = 274.33 days), 30 mothers participated. At both time points, the mothers participated in a Stroop task with infant crying and white noise as the stimuli. They were instructed to answer the color out loud as quickly and accurately as possible, while ignoring the sound. Four types of audio stimuli were used in this task (the cry of the mother's own infant, the cry of an unfamiliar infant, white noise matched to the cry of the mother's own infant, and white noise matched to the cry of an unfamiliar infant), one of which was presented randomly before each trial. Response time and the correct response rate for each condition were the dependent variables. Results: For response time, the main effect of familiarity was significant, with longer response times when the participant's infant's cry was presented. In addition, response times were lower at Time 2 than at Time 1 in some conditions in which crying was presented. Discussion: The results suggest that mothers may be less disturbed by infant crying as they gain more experience. Elucidating the characteristics of postpartum mothers' changes in cognitive performance related to infants' cries would be useful in fundamental and applied research to understand the process of parents' adaptation to parenting.

Impact of visiting restrictions on Edinburgh postnatal depression scale screening scores at one month postpartum during the spread of COVID-19: a single-center case-control study in Japan.

BACKGROUND: This study aimed to evaluate whether "visiting restrictions" implemented due to the coronavirus disease 2019 (COVID-19) pandemic are a risk factor for postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS). METHODS: This case-control study participants who gave birth during the spread of COVID-19 (COVID-19 study group) and before the spread of COVID-19 (control group). Participants completed the EPDS at 2 weeks and 1 month after childbirth. RESULTS: A total of 400 cases (200 in each group) were included in this study. The EPDS positivity rate was significantly lower with visiting restrictions than without (8.5% vs.18.5%, p = 0.002). Multivariate analysis of positive EPDS screening at the 1st month checkup as the objective variable revealed that visiting restrictions (odds ratio (OR): 0.35, 95% confidence interval (CI): 0.18-0.68), neonatal hospitalization (OR: 2.17, 95% CI: 1.08-4.35), and prolonged delivery (OR: 2.87, 95% CI: 1.20-6.85) were factors associated with an increased risk of positive EPDS screening. CONCLUSION: Visiting restrictions on family during the hospitalization period for delivery during the spread of COVID-19 pandemic did not worsen EPDS screening scores 1 month postpartum, but stabilized the mental state of some mothers.

Evaluation of calcification distribution by CT-based textural analysis for discrimination of immature teratoma.

BACKGROUND: Mature and immature teratomas are differentiated based on tumor markers and calcification or fat distribution. However, no study has objectively quantified the differences in calcification and fat distributions between these tumors. This study aimed to evaluate the diagnostic potential of CT-based textural analysis in differentiating between mature and immature teratomas in patients aged < 20 years. MATERIALS AND METHODS: Thirty-two patients with pathologically proven mature cystic (n = 28) and immature teratomas (n = 4) underwent transabdominal ultrasound and/or abdominal and pelvic CT before surgery. The diagnostic performance of CT for assessing imaging features, including subjective manual measurement and objective textural analysis of fat and calcification distributions in the tumors, was evaluated by two experienced readers. The histopathological results were used as the gold standard. The Mann-Whitney U test was used for statistical analysis. RESULTS: We evaluated 32 patients (mean age, 14.5 years; age range, 6-19 years). The mean maximum diameter and number of calcifications of immature teratomas were significantly larger than those of mature cystic teratomas (p < 0.01). The mean number of fats of immature teratomas was significantly larger than that of mature cystic teratomas (p < 0.01); however, no significant difference in the maximum diameter of fats was observed. CT textural features for calcification distribution in the tumors showed that mature cystic teratomas had higher homogeneity and energy than immature teratomas. However, immature teratomas showed higher correlation, entropy, and dissimilarity than mature cystic teratomas among features derived from the gray-level co-occurrence matrix (GLCM) (p < 0.05). No significant differences were observed in the CT features of fats derived from GLCM. CONCLUSION: Our results demonstrate that calcification distribution on CT is a potential diagnostic biomarker to discriminate mature from immature teratomas, thus enabling optimal therapeutic selection for patients aged < 20 years.

Attitudes toward cancer screening in regional Japan during the COVID-19 pandemic: An anonymous survey.

The coronavirus disease (COVID-19) pandemic has raised concerns about the impact of delayed health check-ups and cancer screenings on cancer diagnosis and treatment. This study aimed to investigate the awareness of cancer patients on future screening measures during the pandemic in rural Japan. An anonymized open-data survey was undertaken in Fukui Prefecture, a rural region of Japan, in 2021. Participants were asked about their cancer screening history, screening frequency during the pandemic, and reasons for not undergoing screening. Among the 1262 respondents, the proportion of patients who underwent cancer screening in 2020 during the pandemic was similar to the proportion who underwent regular (annual or biannual) screening in 2019 before the pandemic. Of those who underwent regular screening, 82% still underwent screening in 2020, while only 21% of those who had irregular screenings. The number of respondents who believed they were healthy and did not require screening increased over time, possibly due to restrictions on going out and refraining from activities during the pandemic. This study in rural Japan found that regular cancer screening prior to the pandemic was associated with a more positive attitude toward screening during the pandemic. Raising awareness about the importance of cancer screening and encouraging participation is crucial for promoting positive attitudes in the future. The findings highlight the need for continued efforts to ensure access to screening services during the pandemic and future public health emergencies.

A 41-Year-Old Woman with Spontaneous Hemoperitoneum in Pregnancy at 28 Weeks.

BACKGROUND Spontaneous hemoperitoneum in pregnancy (SHiP), defined as nontraumatic, acute intra-abdominal bleeding during pregnancy or the postpartum period, is a serious life-threatening complication to mother and child. Endometriosis is a major risk factor for SHiP. This study presents the case of a 41-year-old woman with adenomyosis who developed hemoperitoneum due to endometriosis at 28 weeks of pregnancy. CASE REPORT The patient was a 41-year-old woman (gravida 1, para 0) who conceived via artificial insemination. She had diffuse adenomyosis in the posterior uterine wall and was admitted to our hospital at 12 weeks of gestation with persistent lower abdominal pain. She had started treatment with hydroxyprogesterone caproate to reduce the focal inflammation of adenomyosis. At 28 weeks of gestation, she developed severe lower abdominal pain, and ultrasonography revealed prolonged fetal heart rate deceleration. An emergency cesarean delivery was performed, and a 907 g female infant with an Apgar score of 2/3 was delivered. Umbilical artery blood pH was 7.15. Bleeding from the veins surrounding an endometriotic lesion on the posterior wall of the uterus was observed, and SHiP was diagnosed. CONCLUSIONS Pregnancies complicated by endometriosis or adenomyosis require perinatal management, considering the possibility of SHiP complication. If acute abdominal pain and fetal heart rate deceleration occur during pregnancy, a search for intra-abdominal bleeding should be performed and emergent open hemostasis or cesarean delivery should be considered.

Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report.

Background: Left ventricular noncompaction (LVNC) is a rare inherited cardiomyopathy with a broad phenotypic spectrum. The genotype-phenotype correlations in fetal-onset LVNC have not yet been fully elucidated. In this report, we present the first case of severe fetal-onset LVNC caused by maternal low-frequency somatic mosaicism of the novel myosin heavy chain 7 (MYH7) mutation. Case presentation: A 35-year-old pregnant Japanese woman, gravida 4, para 2, with no significant medical or family history of genetic disorders, presented to our hospital. In her previous pregnancy at 33 years of age, she delivered a male neonate at 30 weeks of gestation with cardiogenic hydrops fetalis. Fetal echocardiography confirmed LVNC prenatally. The neonate died shortly after birth. In the current pregnancy, she again delivered a male neonate with cardiogenic hydrops fetalis caused by LVNC at 32 weeks of gestation. The neonate died shortly after birth. Genetic screening of cardiac disorder-related genes by next-generation sequencing (NGS) was performed which revealed a novel heterozygous missense MYH7 variant, NM_000257.3: c.2729A > T, p.Lys910Ile. After targeted and deep sequencing by NGS, the same MYH7 variant (NM_000257.3: c.2729A > T, p.Lys910Ile) was detected in 6% of the variant allele fraction in the maternal sequence but not in the paternal sequence. The MYH7 variant was not detected by conventional direct sequencing (Sanger sequencing) in either parent. Conclusions: This case demonstrates that maternal low-frequency somatic mosaicism of an MYH7 mutation can cause fetal-onset severe LVNC in the offspring. To differentiate hereditary MYH7 mutations from de novo MYH7 mutations, parental targeted and deep sequencing by NGS should be considered in addition to Sanger sequencing.

Zinc deficiency is associated with the development of ovarian endometrial cysts.

Ovarian cancers derived from endometrial cysts, also known as endometriosis in ovaries, are widespread histological types in Japan. Several studies suggest that zinc deficiency plays a role in endometriosis; however, the biological mechanism of zinc deficiency and endometrial cyst remains unknown. Thus, we investigated the association between zinc status and endometrial cysts. We measured the serum zinc levels in patients who had undergone surgery for endometrial cysts (n=19) and non-endometrial benign cysts (n=36). We analyzed cell proliferation, microarray data, and gene expression using N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chelator, in human immortalized endometrial epithelial cells (EMosis). The endometrial cyst group had considerably lower serum zinc levels than the non-endometrial benign cyst group. After adjusting for age, body mass index, alcohol consumption, smoking, and supplement use, endometrial cysts were markedly associated with serum zinc levels. EMosis cells treated with 5 µM TPEN demonstrated extensively increased proliferation compared to untreated cells. In the microarray analysis of EMosis cells treated with 5 µM TPEN, the enriched cellular components contained nucleoplasm, nuclear parts, and nuclear lumen. The upregulated biological processes included responses to hypoxia and decreased oxygen levels. The upregulated Kyoto Encyclopedia of Genes and Genomes pathway included the hypoxia-inducible factor-1 signaling pathway. EMosis cells treated with 5 µM TPEN demonstrated increased activator 1 (SRA1) expression and decreased AT-rich interaction domain 1A (ARID1A) expression. Protein-protein interaction network analysis indicated that ARID1A and SRA1 were associated with SMARCD1 and ATF1 among the differentially expressed genes in the microarray. EMosis cells treated with 5 µM TPEN revealed increased SRA1 mRNA levels and decreased ARID1A mRNA expression, whereas EMosis cells treated with 5 µM TPEN together with 10 µM zinc did not reveal changes in the mRNA levels of SRA1 or ARID1A compared with those without TPEN. These results suggest that zinc deficiency contributes to endometrial cyst development. Accordingly, zinc supplementation may suppress endometrial cyst development.

Comparison of older and younger patients with ovarian cancer: A post hoc study (JGOG3016-A3) of the treatment strength and prognostic outcomes of conventional or dose-dense chemotherapy.

AIM: To evaluate changes of treatment strength and its impact on prognosis in older patients with ovarian cancer. METHODS: We compared relative dose intensity (RDI) as a representative of treatment strength, prognosis, and other features between older (≥65 years) and younger patients (<65 years) retrospectively. Seventy-seven older patients of 301 who received dose-dense-paclitaxel-carboplatin (dTC) and 93 older patients of 304 who received conventional-paclitaxel-carboplatin (cTC) from the Japanese Gynecologic Oncology Group (JGOG) 3016 clinical trial were analyzed. RESULTS: The RDI of older patients was lower than that of younger patients in cTC (87.4% vs. 90.8%, p = 0.009) but not in dTC (79.0% vs. 81.2%, p = 0.205). In both regimens, older patients had worse overall survival than younger patients: hazard ratio [HR] = 1.80; 95% confidence interval [CI]: 1.25-2.59; p = 0.001 for dTC, and HR = 1.59; 95% CI: 1.15-2.19; p = 0.04 for cTC. However, the RDI was not determined as a prognostic factor statistically. The prognostic factors identified by multivariate analysis for both regimens were clinical stage and residual disease; for dTC were age, performance status, and serum albumin; and for cTC was white blood cell count. There was no difference in neutropenia observed between age groups in either regimen. CONCLUSIONS: The RDI of older patients varies according to the administered schedule and is not always lower than that of younger patients. Older patients with comparable treatment strength to younger patients in the dTC group did not accomplish the same level of prognosis as younger patients. Other biologic factors attributable to aging may affect prognosis.

Impact of maternal late hospital arrival on adverse outcome of offspring affected by placental abruption: A regional multicenter nested case-control study in Japan.

AIMS: To elucidate the influence of the time-intervals between the onset and arrival (TIME 1), onset and delivery (TIME 2), and the decision to deliver and delivery (TIME 3) on severe adverse outcomes of offspring born to mothers complicated by placental abruption outside the hospital. METHODS: This is a multicenter nested case-control study about placental abruption at Fukui Prefecture, a regional area in Japan, through 2013 to 2017. Multiple pregnancy, fetal or neonatal congenital abnormality, and unknown detailed information at onset of placental abruption were excluded. A composite of perinatal death and cerebral palsy or death at 18-36 months of corrected age was defined as the adverse outcome. The relationship between time-intervals and the adverse outcome was analyzed. RESULTS: The 45 subjects for analysis were divided into two groups, including a group with and without adverse outcome (poor, n = 8; and good, n = 37). TIME 1 was longer in the poor group (150 vs. 45 min, p < 0.001). A subgroup analysis targeted to 29 cases with preterm birth at the third trimester indicates that TIME 1 and TIME 2 were longer in the poor group (185 vs. 55 min, p = 0.02; and 211 vs. 125 min, p = 0.03), while TIME 3 was shorter in the poor group (21 vs. 53 min, p = 0.01). CONCLUSIONS: Long time-intervals between onset and arrival or onset and delivery may be correlated with perinatal death or cerebral palsy in surviving infants affected by placental abruption.