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Both ligand-dependent and ligand-independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation and results in activation of the ERα-dependent pathways that are involved in endometrioid endometrial cancer ( EEC) pathogenesis. It is also known that the mammalian target of rapamycin ( mTOR)/p70 S6 kinase 1 ( S6K1) and MAPK/p90 ribosomal S6 kinase ( RSK) signaling pathways coordinately regulate phosphorylated- ERα at Ser167 (p-Ser167- ERα). However, the expression of p-Ser167- ERα in EEC and its prognostic role in ECC is largely unexplored. The purpose of the present study was to investigate the expression of p-Ser167- ERα in ECC and its relationship with prognosis. Immunohistochemical staining of primary EEC surgical specimens ( n = 103) was carried out using antibodies specific for p-Ser167- ERα and for p- mTOR/p-S6K1 and p- MAPK/p- RSK. The correlation of p-Ser167- ERα expression with clinicopathological features and survival of ECC was studied. Patients that were positive for nuclear p-Ser167- ERα had significantly shorter relapse-free survival, and although the result was not significant, levels of nuclear p-Ser167-ERα tended to be higher in advanced-stage ECC patients. Nuclear p-Ser167- ERα was significantly positively correlated with p- MAPK and p- S6K1, and with significantly shorter relapse-free survival in EEC. [ABSTRACT FROM AUTHOR]

Purpose: Pathological data suggest that the rate of oestrogen receptor (ER) expression in uterine sarcoma is significantly lower than in leiomyoma. The present study aimed to investigate whether ER expression using ER imaging agents for positron emission tomography (PET), of which the most successful has been 16α-[F]-fluoro-17β-oestradiol (FES), is able to add useful information to the differential diagnosis of uterine sarcoma and leiomyoma in patients with positive or equivocal findings on [F]fluorodeoxyglucose (FDG) PET. Methods: A total of 76 patients with suspected uterine sarcoma based on ultrasound and magnetic resonance imaging findings from 2007 to 2010 were enrolled. Twenty-four of the present patients were referred for FES PET because of FDG PET findings that showed equivocal or positive FDG uptake. PET images were quantitatively evaluated with reference to histopathological findings. Receiver-operating characteristic analysis was performed to determine the optimal cutoff value to differentiate uterine sarcoma and leiomyoma. Results: Of the 24 patients, 11 had a final diagnosis of uterine sarcoma, while 13 had leiomyoma. The sensitivity, specificity and accuracy of an FDG to FES standardized uptake value (SUV) ratio greater than 2.0 were significantly higher using Cochran's Q test ( p = 0.024) when compared with FDG PET greater than 3.0 alone (90.9 vs 81.8%, 92.3 vs 84.6% and 91.3 vs 83.3%, respectively). Conclusion: Additional FES PET findings confirmed uterine sarcoma in 91.3% of a selected group of patients with equivocal or positive FDG uptake. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between uptake of 16α-[F]fluoro-17β-oestradiol (FES) and expression of oestrogen receptors as well as other related immunohistochemistry markers, positron emission tomography (PET) was performed in patients with endometrial carcinoma before surgery. Methods: Nineteen patients with endometrioid adenocarcinoma underwent preoperative PET studies with FES and 2-[F]fluoro-2-deoxy- D-glucose (FDG). Standardized uptake values (SUVs) for each tracer and the regional FDG to FES SUV ratio were calculated using images after coregistration. PET values were compared with postoperative stage, differentiation grade and immunohistochemical scores including oestrogen receptor subtypes (ERα, ERβ), progesterone receptor B (PR-B), Ki-67 and glucose transporter 1 (GLUT1). Results: FES uptake showed a significantly positive correlation with expression of ERα. The FDG to FES ratio showed a significantly negative correlation with expression of ERα and PR-B. The FES uptake and FDG to FES ratio did not correlate with expression of ERβ, Ki-67 or GLUT1. FDG uptake was not correlated with any of the immunohistochemical scores. The PR-B score was strongly correlated with the ERα score. Well-differentiated carcinoma (grade 1) showed a significantly higher FES uptake and significantly lower FDG to FES ratio than moderately or poorly differentiated carcinoma (grade 2-3). None of the PET parameters were significantly different between advanced-stage carcinoma (≥ stage IB) and early-stage carcinoma (IA) based on the Féderation International de Gynécologie et d'Obstétrique (FIGO) staging classification. Differentiation grade was the most closely correlated parameter to FES uptake and FDG to FES ratio by multivariate analyses. Conclusion: FES PET combined with FDG would be useful for non-invasive evaluation of ERα distribution, as well as ERα function, which reflects differentiation grade in endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Massive subchorionic hematoma is a localized collection of blood or hematoma in the placenta, and can result in serious obstetrical complications. The condition can be diagnosed antenatally by ultrasound. However, no reports have previously described the same condition featuring an intraplacental fluid–fluid level on imaging studies. We report a case of massive subchorionic hematoma diagnosed prenatally, and propose an additional peculiar finding detectable on both the ultrasound and magnetic resonance images: the intraplacental fluid–fluid level. We also review previously reported cases that were detected by ultrasonography. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Objective: In endometrial cytology, differentiating endometrial glandular stromal breakdown (EGBD) from endometrial endometrioid carcinoma (G1-EEC) is often difficult. In this study, we provided a new focus on chondroitin sulfate (CS), a major substrate component of the endometrial stroma, and assessed the diagnostic utility of Alcian Blue (AB) staining in the differential diagnosis in liquid-based cytological (LBC) samples., Materials and Methods: LBC specimens from 19 patients with a proliferative endometrium, 36 with EGBD, and 30 with G1-EEC who underwent endometrial cytology were stained with AB (pH 1.0), and their reactivity was observed. In addition, immunocytochemical staining of CS and CD31 was performed for five cases each to evaluate their interrelationship with blood vessels., Results: Regarding the 30 G1-EEC cases, at least one of the three representative staining patterns was observed by AB staining: dot-like, microtubular, and finely branched linear patterns. Moreover, the inner portion of the tubular material observed by AB staining expressed CD31. Conversely, in the 36 EGBD cases, only five metaplastic clusters with irregular protrusions and condensed stromal clusters (CSCs) showed a dot-like positive pattern, and background CSCs did not show reactivity to AB staining in any of the cases. Furthermore, the vascular structure expressing CD31 in cell clusters was also unclear., Conclusions: We demonstrated that AB staining shows different staining patterns in G1-EEC and EGBD, reflecting their different tissue structures. Our data provide new insights into endometrial cell diagnosis changes and demonstrate that AB staining is a potential new diagnostic aid tool for the differentiation of G1-EEC from EGBD., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Cytology.)

Objective: In Japan, no region has introduced primary HPV testing for cervical cancer screening. We assessed the diagnostic value and possible harm of HPV testing in Japan., Methods: This cross-sectional study with historical controls used cytology-based screening and co-testing data in Japan. As surrogate indicators of possible harm, colposcopy referral rate and cervical intraepithelial neoplasm (CIN) 1 detection rates were calculated. As surrogate indicators with diagnostic values, the detection rates of CIN2 or greater (CIN2+) and CIN3+ were calculated., Results: The data of 297 970 women (182 697 for cytology-based, 115 273 for co-testing) were examined. The detection rates of CIN1, CIN2+, and CIN3+ were significantly higher in the co-testing group than in the cytology-based group (P < 0.001, P < 0.0001, P < 0.01, respectively). Between ages 25-49, CIN2+ detection rates were significantly higher in the co-testing group than in the cytology-based group (P < 0.05 for each 5-year age group). Between ages 30-49, CIN3+ detection rates were significantly higher in the co-testing group than in the cytology-based group (P < 0.05 for each 5-year age group)., Conclusion: Limiting the target age group may minimize the possible harm of screening. Cytology/HPV co-testing may be useful in Japanese populations if balance is maintained between benefit and harm., (© 2021 International Federation of Gynecology and Obstetrics.)

Background: To adopt HPV self-sampling in Japan, we assessed the concordance between self- and physician-collected human papillomavirus (HPV) samples from Japanese patients and examined the performance of HPV self-sampling for cervical intraepithelial neoplasia grade 2 or worse (CIN2+)., Methods: Patients who had previously tested negative for intraepithelial lesions or malignancy/HPV-positive, and patients with atypical squamous cells of undetermined significance or worse (ASCUS+) cytology were eligible for this cross-sectional study. Participants performed HPV self-sampling using an Evalyn brush, which was submitted at the Fukui Prefectural Health Care Association. The Evalyn brush heads were stored in ThinPrep vials. The physician, however, performed HPV and cell sampling using an endocervical brush and immediately stored the brush heads in ThinPrep vials. All participants underwent colposcopy and biopsy. Histopathological diagnoses were made by pathologists at Fukui University Hospital. HPV infection was confirmed using a PCR-based Cobas 4800 HPV DNA test. Cytological analysis was performed at Fukui Prefectural Health Care Association., Results: HPV-positive rates for physician-collected samples and self-collected samples were 51 and 50%, respectively. The perfect match rate of HPV type between the groups was 88% (κ = 0.76). HPV16/18 showed higher agreement rates than other HPVs (99%, kappa 0.96 and 89% kappa 0.77, respectively). Both groups showed 100% sensitivity to CIN2+, but specificity was 57.0 and 58.1%, respectively., Conclusion: For HPV typing, a good concordance rate was seen between self- and physician-collected samples. Self-sampling showed high sensitivity for CIN2+. Self-sampling using the Evalyn brush and Cobas 4800 may be feasible for screening Japanese individuals.

Objective: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer., Methods: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy., Results: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged., Conclusion: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: The aim of this study was to determine whether a preoperative health status index and intraoperative data could predict perioperative morbidity and mortality in women over the age of 65 years undergoing surgery for gynecologic disorders., Methods: The medical records of 68 female patients who were ≥65 years of age and who underwent surgery under general anesthesia in our institute from January 2014 to December 2015 were retrospectively reviewed. Preoperative data were extracted from a database and included comorbidities, American Society of Anesthesiologists physiological status classification, the Charlson Comorbidity Index, the Subjective Global Assessment 2011 revision, the subjects' risk of falling, body mass index, and age. The intraoperative factors investigated included the type of surgery and the Surgical Apgar Score (SAS). Major postoperative complications were defined as > Grade 3 based on the Clavien-Dindo classification version 2.0., Results: Of the 68 elderly gynecological patients, 6 (8.8%) developed serious Grade 3 or worse complications within 30 days of surgery. The only factor that significantly affected postoperative complications was the SAS, an index of the patient's intraoperative condition. The optimum cut-off SAS for the occurrence of complications was determined by the receiver operating characteristic curve to be ≤ 6 points; a score ≤6 points predicted the development of postoperative complications with 66.7% sensitivity and 79.0% specificity., Conclusion: In this study, the SAS predicted the development of serious complications in elderly gynecological patients within 30 days of surgery more accurately than did other comorbidities, preoperative assessments, and type of surgery., (Copyright © 2017. Published by Elsevier Ltd.)

Unlabelled: The aim of this study was to investigate the relationship between the tumor uptake of 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) and (18)F-FDG using PET and expressions of sex hormone receptors, such as estrogen receptor (ER), as well as glucose transporter 1 (GLUT-1) and Ki-67 analyzed by the immunohistochemistry method in mesenchymal uterine tumors., Methods: Forty-seven patients with mesenchymal uterine tumors were studied with (18)F-FES and (18)F-FDG PET. Postoperative pathologic diagnosis revealed 33 uterine leiomyomas and 14 uterine sarcomas. Tissue samples were assayed for expression of ERα, ERβ, progesterone receptor (PR), PR-B, GLUT-1, and Ki-67 by an immunohistochemistry method. Standardized uptake values (SUVs) for (18)F-FES and (18)F-FDG were compared with the semiquantitative immunoreactive score (0-12) and quantitative labeling index (LI) for Ki-67 in immunohistochemistry., Results: (18)F-FES uptake was significantly lower (P < 0.001) and the (18)F-FDG uptake and SUV ratio of (18)F-FDG to (18)F-FES ((18)F-FDG/(18)F-FES ratio) (P < 0.005 and P < 0.001, respectively) were significantly higher in uterine sarcomas than in leiomyomas. Immunohistochemistry analysis showed significantly higher expressions of ERα, PR, and PR-B in uterine leiomyomas than in sarcomas. The Ki-67 LI was significantly greater in uterine sarcomas than in leiomyomas. Correlation analysis for all tumors showed positive correlations between (18)F-FES SUV and immunohistochemistry scores of ERα, PR (P < 0.001), and PR-B (P < 0.005) as well as between (18)F-FDG SUV and GLUT-1 and Ki-67 (P < 0.001). However, the (18)F-FDG/(18)F-FES ratio showed significantly negative correlations with ERα, PR (P < 0.001), and PR-B (P < 0.005) and a positive correlation with Ki-67 LI (P < 0.001). In uterine sarcomas, ERα and (18)F-FES SUV showed a positive correlation (P < 0.001) in a low SUV range, and the (18)F-FDG/(18)F-FES ratio showed positive correlations with ERβ and GLUT-1 expression (P < 0.005)., Conclusion: (18)F-FES and (18)F-FDG PET showed correlations between tracer uptake and expressions of sex hormone receptors, GLUT-1, and Ki-67 in mesenchymal uterine tumors. The (18)F-FDG/(18)F-FES ratio was correlated with Ki-67, GLUT-1, and ERβ in uterine sarcoma. Functional PET imaging and PET parameters would be useful noninvasive biomarkers for the assessment of tumor hormone receptor expression, glucose metabolism, and proliferation and for differential diagnosis of uterine leiomyoma and sarcoma.

Cisplatin is one of the most potent antitumor agents for ovarian cancer, but has also been implicated in normal tissue cytotoxicity. We examined the effect of cisplatin alone and in combination with C16Y, a newly-identified anti-angiogenic peptide from the NH2-terminal domains of the γ-chain of laminin-1, on the modulation of Bcl-2/Bax expression and induction of apoptosis in ovarian cancer cells (OVACAR3). C16Y did not elicit cell death of human umbilical vein endothelial cells (HUVECs). Cisplatin exerted a lethal effect with an EC50 of 10 µM in OVACAR3s. In the presence of 25 or 50 µg/ml of C16Y (a range which has no effect against HUVECs), the EC50 for cisplatin in OVACAR3s decreased to 3.5 and 2.0 µM, respectively. Using fluorescence-activated cell sorting (FACS) analysis of DNA stained OVACAR3s and terminal deoxynucleotide tranferase-mediated dUTP nick end-labeling (TUNEL), we found that even at concentrations of 1 and 3 µM cisplatin, C16Y at 10 and 25 µg/ml increased the incidence of apoptosis in OVACAR3s by 3-5-fold. Each drug had some measurable effect on Bax protein expression. Furthermore, Bcl-2 protein expression levels were markedly reduced by C16Y alone and cisplatin alone in a dose-dependent manner. The combination of C16Y and cisplatin resulted in a further dramatic reduction in Bcl-2, underscoring the pronounced synergy produced by cisplatin and C16Y together. On the other hand, C16Y did not activate any other signal transduction pathways that usually culminate in the activation of apoptosis, such as the p53, p21waf1, p73, ERK1/2 or PI3-AKT pathways. These observations suggest that the suppression of the Bcl-2/Bax ratio may play an important role in mediating the synergistic effect of cisplatin and C16Y on the induction of apoptosis in OVACAR3 cells.

Objective: The purpose of this study was to determine whether the addition of positron emission tomography (PET) with the radiotracer FDG to cross-sectional imaging, such as CT, increases accuracy in the detection of tumor spread. SUBJECTS AND METHODS. Fifteen patients who were thought to have ovarian cancer on the basis of the results of physical examination, sonography findings, and level of serum cancer antigen 125 were enrolled over an 11-month period. After screening, patients underwent two imaging examinations-abdominopelvic CT and whole-body FDG PET- within 2 weeks before surgery. Also before surgery, staging accuracy was assessed separately using CT with or without FDG PET (which was based on modifications of the International Federation of Gynecology and Obstetrics [FIGO] criteria). The results of the histology and surgery findings were used to assess the accuracy of the scanning findings., Results: Staging revealed stage III disease in seven patients (IIIC, n = 6; IIIB, n = 1), stage II in three (IIC, n = 2; IIB, n = 1), and stage I in five (IC, n = 3; IA, n = 2), according to the FIGO criteria. Although CT staging correlated with postoperative staging in eight (53%) of 15 patients, consensus evaluation of CT with FDG PET staging improved correlation with postoperative staging in 13 (87%) of 15 patients., Conclusion: The addition of FDG PET to CT increases accuracy in staging of ovarian cancer.