Consistency in human papillomavirus type detection between self-collected vaginal specimens and physician-sampled cervical specimens.

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.

Real-world efficacy and safety of low-dose pembrolizumab in patients with advanced and refractory gynecologic cancers.

OBJECTIVE: The approved standard dose of pembrolizumab (200 mg administrated every 3 weeks) for cancer treatment imposes a significant financial burden on patients. However, no study has analyzed the clinical outcomes of low-dose pembrolizumab among individuals diagnosed with gynecologic cancer. The primary objective of this study was to assess the effectiveness and safety of a low-dose pembrolizumab regimen in real-world clinical practice. METHODS: We retrospectively assessed the efficacy and safety data of patients with gynecologic malignancies who received pembrolizumab between 2017 and 2022 at Kaohsiung Chang Gung Memorial Hospital. Furthermore, we conducted a comparative analysis of the objective response rate (ORR) and progression-free survival (PFS) between patients with deficient mismatch repair (dMMR) and proficient MMR (pMMR). RESULTS: A total of thirty-nine patients were included and received pembrolizumab at fixed dosages of 50 mg (5.1%), 100 mg (84.6%) and 200 mg (10.3%) per cycle. Compared to the pMMR group, the dMMR group exhibited a tendency toward improved ORR (45.5% vs. 13.0%, p = 0.074), and notably, the median duration of response remained unreached. There was no significant difference in PFS between the dMMR and pMMR groups; however, the patients with dMMR in tumor tissue had a trend of better survival (p = 0.079). Incidence of immune-related adverse events (irAEs) of any grade was observed in 13 patients (33.3%), with 3 individuals (7.7%) experiencing grade 3 or 4 events. CONCLUSION: Low-dose pembrolizumab may be a cost-effective and safe treatment option without compromising clinical outcomes in patients with refractory gynecologic cancers.

Estrogen/Progesterone Receptor Expression and Cancer Antigen 125 Level as Preoperative Predictors to Estimate Lymph Node Metastasis in Endometrioid Endometrial Cancer.

Loss of estrogen receptor/progesterone receptor (ER/PR) in endometrial cancer (EC) is associated with tumor progression and poor outcomes. Elevated pretreatment cancer antigen 125 (CA 125) level is a risk factor for lymph node metastasis (LNM). We evaluated whether the combination of ER/PR expression and CA 125 level could be used as a biomarker to predict LNM. We retrospectively investigated patients with endometrioid EC who underwent complete staging surgery during January 2015 to December 2020. We analyzed ER/PR status using immunohistochemical staining, and quantified its expression using the sum of both ER/PR H-scores. Receiver operating characteristic curves were used to identify optimal cutoff values of H-score and CA 125 levels for predicting LNM. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. In 396 patients, the optimal cutoff values of the ER/PR H-score and CA 125 were 407 (area under the receiver operating characteristic curve: 0.645, P=0.001) and 40 U/mL (area under the receiver operating characteristic curve: 0.762, P<0.001), respectively. Multivariate analysis showed that CA 125 ≥40 UmL (odds ratio: 10.02; 95% CI: 4.74-21.18) and ER/PR H-score <407 (odds ratio: 4.20; 95% CI: 1.55-11.32) were independent predictors. An LNM predictive nomogram was constructed using these 2 variables and our model yielded a negative predictive value and negative likelihood ratio of 98.3% and 0.14, respectively. ER/PR expression with pretreatment CA 125 levels can help estimate LNM risk and aid in decision-making regarding the need for lymphadenectomy in patients with endometrioid EC.

Comprehensive Clinicopathologic Analysis for Mismatch Repair Protein Expression in Unselected Endometrial Carcinoma Patients With an Emphasis on the Role of MLH1 Deficiency.

Screening for mismatch repair (MMR) deficiency in unselected patients with endometrial carcinoma (EC) and the clinicopathologic descriptions of ECs with MMR deficiency have been well demonstrated in Western populations, but studies on Asian populations are relatively scarce. In this study, we described the clinicopathologic features of ECs according to MMR status in unselected Taiwanese patients. We also conducted subgroup analysis of MMR-deficient (dMMR) cases according to the presence or absence of MLH1. Patients diagnosed with ECs between January 2017 and February 2020 at our institution were included. Immunohistochemistry analysis of MLH1, PMS2, MSH2, and MSH6 proteins on endometrial primary tumors and clinicopathologic variables were assessed retrospectively. A total of 231 EC patients were enrolled, of whom 50 (21.6%) had dMMR tumors. Of these 50 cases, 39 had tumors that lacked MLH1 expression and 11 were positive for MLH1. The overall dMMR group was significantly related to older age, parity, and high histologic grade compared with the MMR-proficient (pMMR) group. ECs with MLH1 deficiency were obviously associated with several poor pathologic features, including high histologic grade, lymph node metastasis, and lymphovascular space invasion. Moreover, we first reported that parity and the late age at menopause are strongly correlated with MLH1-related dMMR EC group compared with pMMR group. In conclusion, triaging EC patients into pMMR, MLH1-related dMMR and non-MLH1-related dMMR groups by immunohistochemistry analysis may help clinicians to predict disease behavior and guide further management. The strong association between parity and MLH1-related dMMR ECs warrants further investigation on the underlying mechanism.

Evaluation of sexual dysfunction in gynecologic cancer survivors using DSM-5 diagnostic criteria.

BACKGROUND: In gynecologic cancer survivors, female sexual dysfunction (FSD) remains under-investigated. We attempted to estimate the prevalence of FSD associated with distress in gynecologic cancer survivors using diagnostic and statistical manual of mental disorders fifth edition (DSM-5) diagnostic criteria and to identify women at risk for FSD. METHODS: We conducted a cross-sectional analysis of premenopausal women aged 20-50 with various gynecologic cancers at least one year after treatment between January 2017 and December 2019. Data of sociodemographics and physical conditions were collected via face-to-face interview during outpatient clinic visits. The domains we used to define FSD were based on DSM-5 diagnostic criteria. Statistical analysis was carried out using Student's t test, Chi-square test and multiple logistic regression. RESULTS: A total of 126 gynecologic cancer survivors with a mean age of 42.4 years were included for analysis and 55 of them (43.7%) were diagnosed as having FSD associated with distress based on DSM-5 criteria. More than half of women (65.1%) reported decreased sexual satisfaction after cancer treatment. According to DSM-5 definition, the most common female sexual disorders were sexual interest/arousal disorder (70.9%), followed by genitopelvic pain/penetration disorder (60.0%), and orgasmic disorder (20.0%). In multiple logistic regression model, endometrial cancer diagnosis was the only independent factor predicting less influence of cancer treatment on FSD (OR 0.370; 95% CI 0.160, 0.856). CONCLUSION: The first study to use DSM-5 criteria for estimation of FSD prevalence. This enables clinicians to identify which women are actually needed to seek medical help. A prevalence of 43.7% of FSD associated with distress was found in a group of gynecologic cancer survivors with the most common being sexual interest/arousal disorder. Endometrial cancer survivors were at low risk for developing FSD after treatment.

Synchronous/metachronous endometrial and colorectal malignancies in Taiwanese women: a population-based nationwide study.

INTRODUCTION: Endometrial cancer (EC) and colorectal cancer (CRC) may share a common genetic background. In a subset of patients, the two malignancies can coexist either at the time of diagnosis (synchronous) or develop consequently (metachronous). The purpose of this nationwide, population-based study was to investigate the occurrence and clinical outcomes of synchronous/metachronous EC/CRC in Taiwanese women. MATERIALS AND METHODS: Data for women diagnosed with EC and/or CRC between 2007 and 2015 were retrospectively retrieved from the nationwide Taiwan Cancer Registry. Mortality data were obtained from the National Death Registry. Women with synchronous/metachronous EC/CRC versus EC or CRC were compared in terms of clinical characteristics and outcomes. RESULTS: Of the 62,764 Taiwanese women diagnosed with EC and/or CRC during the study period, 167 (0.3%) had synchronous/metachronous EC/CRC. Among them, 72 cases (43.1%) presented with EC followed by CRC, 66 (39.5%) with CRC followed by EC, and 29 (17.4%) with synchronous EC/CRC. Kaplan-Meier estimates for time-to-event data revealed that the 2-year risk rates of developing a metachronous tumor of interest (CRC or EC) in women diagnosed with an initial EC and CRC were 39.6% and 42.1%, respectively. The 5-year overall survival rates of women with metachronous EC/CRC who had an initial diagnosis of EC, CRC, and synchronous EC/CRC were 73.9%, 70.9%, and 37.0%, respectively. CONCLUSIONS: Endometrial cancer is the most common first tumor in Taiwanese women with metachronous EC/CRC. The 2-year risk rates of developing a metachronous tumor of interest (CRC or EC) in women diagnosed with an initial EC and CRC are not negligible. Surveillance for CRC is recommended for all women diagnosed with EC. The clinical outcomes of synchronous EC/CRC are markedly less favorable.

Effects of Icodextrin Solution (Adept®) on Ovarian Cancer Cell Proliferation in an In Vitro Model.

Background and objective: Anti-adhesion barriers are currently used during ovarian cancer surgery to decrease adhesion-related morbidity. Adept® (4% icodextrin) solution, a liquid anti-adhesion material, has been widely used during gynecologic surgeries, though the risk of this barrier for oncologic surgery is controversial. The aim of this study was to determine the effect of Adept® solution on the proliferation of ovarian cancer cells. Materials and methods: We assessed the dose- and time-dependent effects of icodextrin on the growth and proliferation of OVCAR-3 and A2780 human ovarian tumor cell lines in vitro. Cell growth was determined by cell number counting. Expressions of cell cycle-regulation proteins (cyclin D1 and cyclin B1) were determined using Western blot analysis. Results: Adept® did not significantly increase ovarian cancer cell growth when tested at various concentrations (0, 1, 5, 10, 15, and 20%, equal to 0, 0.04, 0.2, 0.4, 0.6 and 0.8% icodextrin) and different time points (1-3 days) compared to control cells. Moreover, the protein levels of cyclin D1 and B1 were not overexpression-elevated in icodextrin-treated ovarian cancer cells, either with an increasing concentration or with an increasing treated time. These results demonstrated that Adept® does not activate the growth or proliferation of ovarian cancer cells in either a dose- or time-dependent manner. Conclusions: This study supports the use of Adept® solution as a safe anti-adhesion barrier for ovarian cancer surgery, though further in vivo studies are necessary.

Factors associated with the inconsistent diagnosis between frozen section and permanent pathologic examination in borderline ovarian tumors.

AIM: The predictive accuracy of frozen sections for borderline ovarian tumors (BOTs) is suboptimal. The aim of this study was to determine the diagnostic accuracy of BOTs and factors associated with an upgrade to a permanent pathological diagnosis of invasive carcinoma in patients diagnosed with BOTs by frozen section. METHODS: We conducted a retrospective study between 2011 and 2018 at Kaohsiung Chang Gung Memorial Hospital (KCGMH). Two hundred and twenty-five records of eligible patients with a diagnosis of BOT by frozen section or permanent diagnosis were reviewed. Positive predictive value and the diagnostic accuracy of frozen sections were calculated. Univariate and multivariate analyses were used to determine the clinicopathological factors associated with an upgrade of the diagnosis from a borderline tumor to malignancy. RESULTS: The agreement between frozen section and permanent pathological diagnoses was 63.1%, and the positive predictive value was 72.1%. The multivariate analysis revealed that CA-125 level > 136 U/mL (odds ratio [OR] = 2.96, 95% confidence interval [CI] = 1.3-6.9; p = 0.012), and tumor histologic type (clear cell/endometrioid vs. mucinous; OR:32.8, 95% CI = 6.9-154.8, p < 0.001; clear cell/endometrioid vs. serous: OR 48.1, 95% CI = 8.8-261.8, p < 0.001) were independent risk factors for an upgrade of the permanent diagnosis from a BOT to ovarian carcinoma. CONCLUSION: An elevated CA-125 level (over 136 U/mL) and tumor histologic type (clear cell and endometrioid subtypes) were associated with an upgrade in the diagnosis of ovarian tumor from a BOT on frozen section to a permanent diagnosis of malignancy.

The influence of probiotics on genital high-risk human papilloma virus clearance and quality of cervical smear: a randomized placebo-controlled trial.

BACKGROUND: Probiotics has been shown to be effective in reducing vaginal colonization of pathogenic organisms. The aim of this study was to investigate the influence of probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on genital high-risk human papilloma virus (HR-HPV) clearance and quality of cervical smear. METHODS: This was a randomized, double-blinded, placebo-controlled trial. Women with genital HR-HPV infection were randomized into study and control groups. A probiotic or placebo preparation was administered orally (one capsule daily) until negative HR-HPV testing. A cervical smear and HR-HPV tests were performed at the beginning of the study and every 3 months thereafter until a negative result was obtained. RESULTS: A total of 121 women with genital HR-HPV infection were enrolled (62 in the study group and 59 in the control group). There was no significant difference in HR-HPV clearance rate between the two groups (58.1% vs. 54.2%). The only factor predicting HR-HPV clearance was a lower initial viral load (HR 3.214; 95% CI: 1.398, 7.392; p = 0.006). Twenty-two women had a mildly abnormal initial cervical smear and nine had an unsatisfactory smear. At 6 months follow-up, both mildly abnormal cervical smear and unsatisfactory smear rates had decreased significantly in the study group compared to the control group (p = 0.017 and 0.027). CONCLUSIONS: The application of probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 did not influence genital HR-HPV clearance, but may have decreased the rates of mildly abnormal and unsatisfactory cervical smears. TRIAL REGISTRATION: Clinicaltrials.gov NCT01599416 , May, 2012. Retrospectively registered.

Pretreatment Factors Associated with Recurrence for Patients with Cervical Cancer International Federation of Gynecology and Obstetrics Stage IB1 Disease.

BACKGROUND: Pretreatment prognostic information is lacking for patients with cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage IB1 disease. Thus, we attempted to identify a high-risk subgroup among them prior to treatment. METHODS: Cervical cancer FIGO stage IB1 patients who had received curative treatment with various modalities in our institute between January 2004 and December 2010 were enrolled. Pretreatment clinical parameters including age, squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen, hemoglobin (Hb) level, platelet count, histological type, and treatment modality were analyzed for treatment outcomes. RESULTS: One hundred ninety-seven patients were included with a median follow-up of 66 months (range 6-119 months). In Cox regression analysis, only SCC histology (HR 0.457, 95% CI 0.241-0.967, p = 0.017) was an independent factor predicting better disease-free survival (DFS). Among SCC histology, patients with an Hb level less than 12 g/dl and a SCC-Ag level more than 3 ng/ml had worse treatment outcomes. The 5-year DFS rates were 89.2, 69.3, and 44.4% for the patients at low-risk (SCC, Hb >12 g/dl, SCC-Ag ≤3 ng/ml), intermediate-risk (non-SCC), and high-risk (SCC, Hb ≤12 g/dl, SCC-Ag >3 ng/ml), respectively (p < 0.001). CONCLUSION: Non-SCC and SCC histology with both anemia and high pretreatment SCC-Ag level were associated with recurrence. Further validation studies are warranted for clarification.

Integration of pretreatment tumor markers in a nomogram model for prognostic prediction of FIGO stage I endometrial cancer: A multi-institutional cohort study.

OBJECTIVE: Traditionally, the prognosis of patients with FIGO stage I endometrial cancer is determined by clinicopathological risk factors. In this study, we assessed the potential contribution of pretreatment carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) levels to estimating the prognosis of these patients and aimed to develop and validate a prognostic nomogram. METHODS: This retrospective study included patients with FIGO stage I endometrial cancer who underwent treatment between January 2009 and December 2021 in the four institutes of Chang Gung Memorial Hospital. To identify optimal cutoff values of CEA and CA-125 for predicting survival, receiver operating characteristic (ROC) curves were generated, the Kaplan-Meier method was used to estimate survival, and a Cox regression model was used to analyze the independent prognostic factors. Finally, a nomogram and calibration curve were constructed to predict patient survival probability. RESULTS: Of the 1559 patients evaluated, the optimal cutoff values of CEA and CA-125 were 1.44 ng/mL (area under the ROC curve [AUC] 0.601) and 39.77 U/mL (AUC 0.503), respectively. Multivariate Cox regression analysis showed that pretreatment CEA (hazard ratio [HR] 2.11, 95% confidence interval [95% CI] 1.35-3.28), CA-125 (HR 2.07, 95% CI 1.31-3.27), age >70 years (HR 12.54, 95% CI 5.05-31.11), myometrial invasion >50% (HR 1.69, 95% CI 1.03-2.73), non-endometrioid histology (HR 1.83, 95% CI 1.14-2.95), high-grade tumor (HR 2.41, 95% CI 1.46-3.97), and lymphovascular space invasion (HR 2.32, 95% CI 1.26-4.25) were significant variables associated with overall survival. These factors were used to construct the nomogram model, which showed good concordance and accuracy. CONCLUSIONS: Integration of pretreatment CEA and CA-125 in a prognostic nomogram is feasible. Our prediction model has the potential to assist clinicians in guiding appropriate clinical practice.

Pretreatment carcinoembryonic antigen combined with cancer antigen-125 for predicting lymph node metastasis in endometrial carcinoma: a retrospective cohort study.

PURPOSE: To investigate whether the cost-effective, pretreatment tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) can be used to predict lymph node metastasis (LNM) in endometrioid-type endometrial cancer (EC) and to develop a predictive model. METHODS: This was a single-center retrospective study of patients with endometrioid-type EC who underwent complete staging surgery between January 2015 and June 2022. We identified the optimal cut-off values of CEA and CA-125 for predicting LNM using receiver operating characteristic (ROC) curves. Stepwise multivariate logistic regression analysis was used to identify independent predictors. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. RESULTS: The optimal cut-off values of CEA and CA-125 were 1.4 ng/mL (area under the ROC curve (AUC) 0.62) and 40 U/mL (AUC 0.75), respectively. Multivariate analysis showed that CEA (odds ratio (OR) 1.94; 95% confidence interval (CI) 1.01-3.74) and CA-125 (OR 8.75; 95% CI 4.42-17.31) were independent predictors of LNM. Our nomogram showed adequate discrimination with a concordance index of 0.78. Calibration curves for the probability of LNM showed optimal agreement between the predicted and actual probabilities. The risk of LNM for markers below the cut-offs was 3.6%. The negative predictive value and negative likelihood ratio were 96.6% and 0.26, respectively, with moderate ability to rule out the possibility of LNM. CONCLUSION: We report a cost-effective method of using pretreatment CEA and CA-125 levels to identify patients with endometrioid-type EC who are at a low risk for LNM, which may guide decision-making regarding aborting lymphadenectomy.

Characteristics of Cancer-Related Fatigue and an Efficient Model to Identify Patients with Gynecological Cancer Seeking Fatigue-Related Management.

Cancer-related fatigue (CRF) is the most common somatic discomfort in patients with gynecological cancers. CRF is often overlooked; however, it can impair the patients' quality of life considerably. This cross-sectional study aimed to identify the clinical characteristics of CRF in gynecological cancer patients. Questionnaires and the International Classification of Diseases 10th Revision (ICD-10) criteria were used to identify CRF. The enrolled patients were further categorized according to the amount of fatigue-related management received. Of the enrolled 190 patients, 40.0% had endometrial cancer, 28.9% had cervical cancer, and 31.1% had ovarian cancer. On the basis of the ICD-10 diagnostic criteria, 42.6% had non-cancer-related fatigue, 10% had CRF, and 51% had BFI-T questionnaire-based fatigue. Moreover, 77.9% of the study cohort had ever received fatigue-related management. Further analysis showed that patients with endometrial/cervical cancer, International Federation of Gynecology and Obstetrics stage >1, Eastern Cooperative Oncology Group performance status score ≥1, inadequate cancer treatment response, and receiving cancer treatment in the past week had a higher probability of receiving more fatigue-related management. The five-item predictive model developed from these factors may help physicians recognize patients seeking more fatigue-related management more efficiently. This is important as they may suffer from a more profound CRF.

Endocervical-type mucinous borderline tumors are related to endometrioid tumors based on mutation and loss of expression of ARID1A.

Nongastrointestinal-type mucinous borderline tumors have been described as displaying endocervical and serous differentiation and hence have been termed "endocervical-type" mucinous borderline tumors, "mixed-epithelial papillary cystadenoma of borderline malignancy of mullerian type," or "atypical proliferative seromucinous tumors." A striking feature of these tumors is their frequent association with endometriosis, which has been reported in a third to a half of cases. This is an unusual finding, as pure endocervical and serous tumors are not usually associated with endometriosis. ARID1A is a recently identified tumor suppressor, which frequently loses its expression and is mutated in endometrium-related carcinomas including ovarian clear cell, ovarian endometrioid, and uterine endometrioid carcinomas. Although ARID1A mutations and their expression have been studied in gynecologic cancer, the expression pattern of ARID1A has not been investigated in ovarian atypical proliferative (borderline) tumors. In this study, we analyzed ARID1A expression in serous, gastrointestinal-type and endocervical-type (seromucinous) mucinous, and endometrioid atypical proliferative (borderline) tumors using immunohistochemistry and performed mutational analysis in selected cases. We observed loss of ARID1A staining in 8 (33%) of 24 seromucinous tumors. In contrast, ARID1A staining was retained in all the other 32 tumors except in 1 endometrioid tumor (P<0.01). Mutational analysis was performed on 2 representative seromucinous tumors, which showed complete loss of ARID1A. Both tumors harbored somatic inactivating ARID1A mutations. Previous studies have reported loss of expression and/or mutation of ARID1A in 30% to 57% of endometrioid and clear cell carcinomas but only rarely in serous tumors. In summary, these tumors often contain endocervical-type mucinous epithelium, but they typically display papillary architecture, unlike most endocervical neoplasms, and their immunophenotype is different from both endocervical and serous tumors. Moreover, they frequently contain ciliated cells, endometrial-type cells, cells with abundant eosinophilic cytoplasm, and hobnail-shaped cells, all of which can be found in endometrioid tumors. The loss of expression of ARID1A and the presence of inactivating mutations of the ARID1A gene further link this tumor to endometrioid and clear cell tumors, as does the frequent association with endometriosis. Accordingly, we suggest designating these tumors "atypical proliferative (borderline) papillary müllerian tumors" as this designation more accurately reflects their clinicopathologic, immunohistochemical, and molecular genetic features.

High immunohistochemical expression of TGF-ß1 predicts a poor prognosis in cervical cancer patients who harbor enriched endoglin microvessel density.

Endoglin, a coreceptor for transforming growth factor ß1 (TGF-ß1) in vascular endothelial cells, is highly upregulated in tumor vessels and therefore is a specific biomarker for angiogenesis. Some studies have suggested that assessment of tumor angiogenesis may predict cancer response to chemotherapy and radiotherapy. In this study, we attempted to analyze the immunohistochemical expression of endoglin and TGF-ß1 from 80 patients with different International Federation of Gynecology and Obstetrics (FIGO) stages of cervical cancer before they received concurrent chemoradiation and to investigate their prognostic significance. The median follow-up period was 86 months (range, 2-144 months). Endoglin staining was assessed by microvessel density (MVD), whereas TGF-ß1 expression was semiquantified as negative, weakly, or strongly staining. A receiver operating characteristic curve was established for endoglin MVD in predicting survival; the optimal cutoff value was 11.125. With a Cox regression analysis, we found that an advanced FIGO stage (hazard ratio 4.66; 95% confidence interval 2.10-10.32, P<0.001) and endoglin MVD more than 11.125 (hazard ratio 12.21; 95% confidence interval 3.62-41.16, P=<0.001) were independent factors to predict survival. Interestingly, a strong TGF-ß1 expression was significantly associated with poor survival only when the endoglin MVD value was higher than 10. Our study shows that evaluation of endoglin MVD by immunochemistry can be used as an independent prognostic marker for cervical cancer patients receiving concurrent chemoradiation. TGF-ß1 also had an impact on survival only when endoglin MVD was enriched, suggesting its involvement in tumor progression in the later stage of angiogenesis.

Loss of ARID1A expression is an early molecular event in tumor progression from ovarian endometriotic cyst to clear cell and endometrioid carcinoma.

OBJECTIVES: ARID1A is a recently identified tumor suppressor participating in chromatin remodeling. Somatic inactivating mutations of ARID1A and loss of its expression occur frequently in ovarian clear cell and endometrioid carcinomas and in uterine endometrioid carcinomas. Because endometriotic epithelium is thought to be the cell of origin of most ovarian clear cell and endometrioid carcinomas, we undertook an analysis of ARID1A expression of these tumors arising within an endometriotic cyst (endometrioma). MATERIALS AND METHODS: Our immunohistochemical study set consisted of 47 endometriotic cysts containing clear cell carcinoma in 24 cases, well-differentiated ovarian endometrioid carcinoma in 20 cases, and mixed clear cell and endometrioid carcinoma in 3 cases. RESULTS: ARID1A loss was observed in 31 (66%) of 47 carcinomas; and therefore, these cases were informative for determining the temporal sequence of loss of ARID1A expression in tumor progression. In 16 of the 47 cases, ARID1A immunoreactivity was retained in both the endometriotic cyst and the carcinoma; and thus, these cases were not informative. All of the 31 informative cases showed loss of ARID1A immunoreactivity in the carcinoma and in the endometriotic cyst epithelium in direct continuity with the carcinoma but not in the cyst epithelium that was not adjacent to the tumor. CONCLUSIONS: Loss of ARID1A function as shown by loss of expression, presumably due to mutations, is an early molecular event in the development of most ovarian clear cell and endometrioid carcinomas arising in endometriomas.

Traffic air pollution and risk of death from ovarian cancer in Taiwan: fine particulate matter (PM2.5) as a proxy marker.

The relationship between mortality attributed to ovarian cancer and exposure to ambient air pollutants was examined using an ecological design. The study areas consisted of 61 municipalities in Taiwan. Air quality data for recorded concentrations of fine particulate matter (PM2.5) from study municipalities for 2006-2009 were obtained as a marker of traffic emissions. These were used as a proxy for polycyclic aromatic hydrocarbons (PAH) exposure. Age-standardized mortality rates for ovarian cancer were calculated for the study municipalities for the years 1999-2008. A weighted multiple regression model was employed to calculate the adjusted risk ratio (RR) in relation to PM2.5 levels. After adjusting for urbanization level and fertility rate, the adjusted RR values (95% confidence interval [CI]) for ovarian cancer were 1.2 (1.02-1.41) for the municipalities with PM2.5 levels between 30.48 µg/m3 and 39.41 µg/m3 and 1.2 (1.03-1.39) for the municipalities with PM2.5 levels between 39.48 µg/m3 and 51.1 µg/m3, compared to the municipalities with PM2.5 levels less than 30.39 µg/m3. Results showed that individuals who resided in municipalities with higher levels of PM2.5, a proxy measure of PAH, were at an increased risk of death from ovarian cancer compared to those subjects living in municipalities with the lowest PM2.5. The findings of this study warrant further investigation into the role of exposure to air pollutants in the etiology of ovarian cancer development.

Outcomes of hepatitis B immunoglobulin and hepatitis B vaccination in high-risk newborns born to HBeAg-positive mothers.

BACKGROUND: To evaluate the protective efficacy of a hepatitis B (HB) vaccination program in Taiwan among high-risk children. METHODS: Children born to HBeAg-positive mothers from 2001 to 2010 were invited back. Blood samples for hepatitis B virus (HBV) seromarkers were taken and the children underwent hepatobiliary ultrasonography. Perinatal factors including delivery mode and vaccination history were collected from their medical records. According to the results of HBV serological markers, the children were initially classified into five groups: HBV naïve, HB vaccine responder, HBsAg carrier, recovered from HBV infection, and anti-HBc-positive alone. Children in the HBV naïve and anti-HBc-positive alone groups who presented with an anamnestic response after a booster HB vaccine were re-assigned to the vaccine responder and recovered from infection groups, respectively. RESULTS: All of the 196 enrolled children received postnatal hepatitis B immunoglobulin (HBIG) and HB vaccinations, of whom one was HBV naïve (0.5%), 109 were vaccine responders (55.6%), 21 were carriers (10.7%), and 65 recovered from infection (33.2%). Among the 21 carriers, 14 (66.7%) presented in the immunotolerant phase. Cesarean section was the only significant perinatal factor between the carriers (5.3%) and those who recovered from infection (37.7%) (p = 0.007). CONCLUSION: In this study, there was a 43.9% HBV infection rate and 10.7% HBsAg carrier rate in high-risk Taiwanese children even after receiving HBIG and HB vaccinations. C-section may protect newborns from becoming HBsAg carriers, while HBV genotype and time of HBIG injection did not contribute to the HBV carrier rate.

Rare live birth to a 48-year-old woman after embryo transfer with autologous oocyte: A case report.

OBJECTIVE: Advanced maternal age and decreased ovarian reserve have been challenges for assisted reproductive technology (ART). Few cases, using autologous oocytes more than 46-years-old, have previously been reported. We seek to show how the age at which autologous oocytes may successfully be employed may be increasing. CASE REPORT: We report a 47-year-old woman with an anti-Müllerian hormone (AMH) level of 0.24 ng/mL, conceived through in vitro fertilization (IVF) using autologous oocytes. Patient was given an antagonist protocol for ovarian stimulation and one frozen-thawed embryo was transferred. The patient became pregnant. The course of her pregnancy was uneventful and she gave birth to a 3330 gm male baby by cesarean section. CONCLUSION: Technological advances permit women, who previously would have been considered too old to employ an autologous oocyte, to have a successful pregnancy with a live birth.

Quantitative Measurement of Progesterone Receptor Immunohistochemical Expression to Predict Lymph Node Metastasis in Endometrial Cancer.

Background: Previous studies have shown that loss of progesterone receptor (PR) in endometrial cancer (EC) is associated with poor outcomes. Evaluating lymph node metastasis (LNM) is essential, especially before surgical staging. The aim of this study was to investigate the role of PR expression and other clinicopathological parameters in LNM and to develop a prediction model. Methods: We retrospectively evaluated endometrioid-type EC patients treated with staging surgery between January 2015 and March 2020. We analyzed PR status using immunohistochemical staining, and the expression was quantified using the H-score. We identified optimal cut-off values of H-score and CA125 for predicting LNM using receiver operating characteristic curves, and used stepwise multivariate logistic regression analysis to identify independent predictors. A nomogram for predicting LNM was constructed and validated using bootstrap resampling. Results: Of the 310 patients evaluated, the optimal cut-off values of PR H-score and CA125 were 162.5 (AUC 0.670, p = 0.001) and 40 U/mL (AUC 0.739, p < 0.001), respectively. Multivariate analysis showed that CA125 ≥ 40 U/mL (OR: 8.03; 95% CI: 3.44−18.77), PR H-score < 162.5 (OR: 5.22; 95% CI: 1.87−14.60), and tumor grade 2/3 (OR: 3.25; 95% CI: 1.33−7.91) were independent predictors. These three variables were incorporated into a nomogram, which showed effective discrimination with a concordance index of 0.829. Calibration curves for the probability of LNM showed optimal agreement between the probability as predicted by the nomogram and the actual probability. Our model gave a negative predictive value and a negative likelihood ratio of 98.4% and 0.14, respectively. Conclusions: PR H-score along with tumor grade and CA125 are helpful to predict LNM. In addition, our nomogram can aid in decision making with regard to lymphadenectomy in endometrioid-type EC.