Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers. METHOD: A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics. RESULTS: A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival. CONCLUSION: Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer. STUDY REGISTRATION: The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).

Lactobacillus fermentum attenuates the alveolar bone loss in ligature-induced periodontitis in mice.

OBJECTIVE: This study investigated the effects of Lactobacillus fermentum BELF11 on periodontitis in mice (LIP). METHODS: Sixty mice were randomly assigned to a control group (CTL), LIP/PBS group (LIP and PBS applied), or LIP/BELF11 group (LIP and L. fermentum BELF11 applied). For 14 days, PBS or L. fermentum BELF11 was applied twice daily to the mice in the LIP/PBS or LIP/BELF11 group, respectively. After 14 days, radiographic, histological, and pro-inflammatory cytokine assessments were conducted. RESULTS: The LIP/PBS and LIP/BELF11 groups demonstrated greater alveolar bone loss than the CTL group (p < 0.05). The LIP/BELF11 group showed significantly reduced alveolar bone loss on the mesial side compared to the LIP/PBS group. Histologically, the LIP/BELF11 group showed consistent patterns of connective tissue fiber arrangement, lower levels of inflammatory infiltration, less alveolar bone loss, and higher alveolar bone density than the LIP/PBS group, despite showing more signs of destruction than the CTL group. The LIP/BELF11 group also exhibited significantly lower levels of pro-inflammatory cytokines than the LIP/PBS group. CONCLUSIONS: L. fermentum BELF11 inhibits alveolar bone loss and periodontitis progression by regulating pro-inflammatory cytokine production. These findings suggest that L. fermentum BELF11 may be a potential adjunctive therapy in periodontal treatment.

Application of Immune Checkpoint Inhibitors in Gynecological Cancers: What Do Gynecologists Need to Know before Using Immune Checkpoint Inhibitors?

Standard treatments for gynecological cancers include surgery, chemotherapy, and radiation therapy. However, there are limitations associated with the chemotherapeutic drugs used to treat advanced and recurrent gynecological cancers, and it is difficult to identify additional treatments. Therefore, immune checkpoint inhibitor (ICI) therapy products, including PD-1/PD-L1 inhibitors and CTLA-4 inhibitors, are in the spotlight as alternatives for the treatment of advanced gynecological cancers. Although the ICI monotherapy response rate in gynecological cancers is lower than that in melanoma or non-small cell lung cancer, the response rates are approximately 13-52%, 7-22%, and 4-17% for endometrial, ovarian, and cervical cancers, respectively. Several studies are being conducted to compare the outcomes of combining ICI therapy with chemotherapy, radiation therapy, and antiangiogenesis agents. Therefore, it is critical to determine the mechanism underlying ICI therapy-mediated anti-tumor activity and its application in gynecological cancers. Additionally, understanding the possible immune-related adverse events induced post-immunotherapy, as well as the appropriate management of diagnosis and treatment, are necessary to create a quality environment for immunotherapy in patients with gynecological cancers. Therefore, in this review, we summarize the ICI mechanisms, ICIs applied to gynecological cancers, and appropriate diagnosis and treatment of immune-related side effects to help gynecologists treat gynecological cancers using immunotherapy.

Prevalence and Treatment of Vulvar Cancer From 2014-2018: A Nationwide Population-Based Study in Korea.

BACKGROUND: Vulvar cancer is one of the rare gynecologic malignancies. Despite the recent increasing trend of vulvar cancer in western countries due to the increased infection of human papillomavirus, there has been no study for population-based incidence of vulvar cancer in Korea. We aimed to investigate the prevalence and treatment of vulvar cancer in South Korea between 2014 and 2018. METHODS: Data from patients diagnosed and treated with vulvar cancer between 2014 and 2018 were obtained from the Health Insurance Review and Assessment Service/National Inpatient Sample (National In-Patient Sample) in South Korea. RESULTS: A total of 4,636,542 women were identified through the HIRA-NIS database from 2014 to 2018, of which 259 patients were diagnosed and treated for vulvar cancer. The mean age diagnosed with vulvar cancer was 62.82 (± 14.30) years in 2014, 64.19 (± 16.79) years in 2015, and 67.40 (± 14.41) years in 2016. In terms of treatment modalities, the most frequent treatment was surgery only without chemotherapy or radiation therapy. In the age-specific prevalence analysis, vulvar cancer was the most prevalent among those over 70 years old. According to multiple regression analysis, patients' age was significantly associated with the prevalence of vulvar cancer. Vulvar cancer was more prevalent in women with low socioeconomic status (SES) compared to those with high SES in 2018 (OR, 4.242; P < 0.001). CONCLUSION: Considering the high prevalence of vulvar cancer in the elderly, it is necessary to establish a new strategy for early screening and treatment.

Long-term risks of coronary heart disease and cerebrovascular disease in ovarian, uterine and cervical cancer survivors: a nationwide study in Korea.

Only few studies have evaluated the incidence of coronary heart disease (CHD) and cerebrovascular disease (CVD) among gynaecologic cancer survivors. We selected 26,880 gynaecologic cancer patients who underwent health check-ups within 2 years after diagnosis using the Korean National Health Insurance Service Database. They were compared with 79,830 non-cancer controls. Cox regression models were used to estimate hazard ratios (HRs). There was no significant relationship between gynaecologic cancer survivors and CHD or CVD events. However, 10 years after diagnosing cancers, the risk of angina increased in cancer survivors (adjusted HR = 1.193, 95% CI: 1.013-1.406). After 1 year of diagnosis, cancer patients with no initial comorbidities showed an increased risk of all CHD and CVD events (adjusted HR = 1.101, 95% CI: 1.020-1.189) and CHD alone (adjusted HR = 1.168, 95% CI: 1.055-1.293) compared with controls. CHD risk was also higher in the cancer group with no comorbidities after 10 years of diagnosis (adjusted HR = 1.284, 95% CI: 1.020-1.615). Overall, the risk of CHD or CVD did not increase in gynaecologic cancer survivors. However, cancer patients without any comorbidities showed a higher risk of CHD compared with control, the risk persisting until 10 years after cancer diagnosis.Impact StatementWhat is already known on this subject? Cardiovascular risk and the incidence of stroke increase after cancer diagnosis.What do the results of this study add? The risk of coronary heart disease (CHD) and cerebrovascular disease did not increase in Asian (especially Korean) gynaecologic cancer survivors compared with the general population. However, cancer patients without any comorbidities showed a higher risk of CHD compared with the non-cancer population.What are the implications of these findings for clinical practice and/or further research? Our results imply the importance of surveillance of cardiovascular risks among patients with gynaecologic cancer without comorbidities.

Females with impaired ovarian function could be vulnerable to environmental pollutants: identification via next-generation sequencing of the vaginal microbiome.

The vaginal microbiome has been widely investigated. However, its relationship with impaired ovarian function has not been evaluated. We conducted a next-generation sequencing (NGS) study of the vaginal microbiome in females with normal and decreased ovarian function and analysed its sensitivity to environmental pollutants. Vaginal swabs were collected from 92 individuals (22 with impaired ovarian function). The 16S rDNA sequences were assembled by FLASH and clustered in OTUs. Diversity analysis was performed using QIIME. The impaired function group showed lower AMH (p < .01) and higher FSH (p = .04). Only two species showed significant differences: Propionibacterium acnes and Prevotella copri. Moreover, more environmental pollutants were related to changes in the vaginal microbiome in the impaired ovarian function group than in the normal group. Vaginal microbiomes in young women with decreased ovarian function tended to be more sensitive to environmental pollutants, especially volatile organic compounds.Impact StatementWhat is already known on this subject? In this study, the possible influence of environmental pollutants, especially volatile organic compounds to ovarian function were identified via next-generation sequencing.What do the results of this study add? This is the first study that shows vaginal microbiomes in young women with decreased ovarian function to be more sensitive to environmental pollutants.What are the implications of these findings for clinical practice and/or further research? The association between impaired ovarian function and environmental pollutants from this study could be helpful when counselling patients with POI.

Pregnancy Outcomes Following Laparoscopic and Open Surgery in Pelvis during Pregnancy: a Nationwide Population-based Study in Korea.

BACKGROUND: Non-obstetric surgery during pregnancy is associated with adverse obstetric and fetal outcomes. The aim of this study was to investigate the risk of adverse pregnancy outcomes for women who underwent non-obstetric pelvic surgery during pregnancy compared with that of women that did not undergo surgery. METHODS: Study data from women who gave birth in Korea were collected from the Korea National Health Insurance claims database between 2006 and 2016. We identified pregnant women who underwent abdominal non-obstetric pelvic surgery by laparoscopy or laparotomy from the database. Pregnancy outcomes including preterm birth, low birth weight (LBW), cesarean section (C/S), gestational hypertension, gestational diabetes, and postpartum hemorrhage were identified. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the pregnancy outcomes were estimated by multivariate regression models. RESULTS: Data from 4,439,778 women were collected for this study. From 2006-2016, 9,417 women from the initial cohort underwent non-obstetric pelvic surgery (adnexal mass resection, appendectomy) during pregnancy. Multivariate logistic regression analysis indicated that preterm birth (HR, 2.01; 95% CI, 1.81-2.23), LBW (HR, 1.62; 95% CI, 1.46-1.79), C/S (HR, 1.13; 95% CI, 1.08-1.18), and gestational hypertension (HR, 1.35; 95% CI, 1.18-1.55) were significantly more frequent in women who underwent non-obstetric surgery during pregnancy compared to pregnant women who did not undergo surgery. When the laparoscopic and laparotomy groups were compared for risk of fetal outcomes, the risk of LBW was significantly decreased in laparoscopic adnexal resection during pregnancy compared to laparotomy (odds ratio, 0.62; 95% CI, 0.40-0.95). CONCLUSION: Non-obstetric pelvic surgery during pregnancy was associated with a higher risk of preterm birth, LBW, gestational hypertension, placenta previa, placental abruption, and C/S. Although the benefits and safety of laparoscopy during pregnancy appear similar to those of laparotomy in regard to pregnancy outcomes, laparoscopic adnexal mass resection was associated with a lower risk of LBW.

Exploring the prognostic significance of preoperative high normocalcemia in epithelial ovarian carcinoma.

PURPOSE: We investigated the association between serum ionized calcium and prognosis of EOC and determined the optimal cutoff value of ionized calcium level to predict the prognosis of EOC. METHODS: The medical records of patients who were newly diagnosed with EOC from 2001 to 2016 were retrieved. Preoperative ionized calcium test was performed within 2 weeks before surgery, and the cutoff of high normocalcemia was defined based on the receiver operating characteristic (ROC) curve for recurrence. Cox proportional hazards regression models were used to identify independent prognostic factors for progression-free survival (PFS). RESULTS: From 2001 to 2016, 83 patients diagnosed with EOC were identified at a single institution. The optimal cutoff value was set to 4.7 mg/dL (high normocalcemia vs. control group) by plotting the ROC curve for recurrence. Stages III/IV were more frequent in high normocalcemia, with borderline significance (72.9% vs. 52.2%, p = 0.053). Recurrence (67.6% vs. 43.5%, p = 0.029) and death (46.0% vs. 15.2%, p < 0.01) were significantly more frequent in the high normocalcemia group. In multivariate analysis, high normocalcemia (HR 1.9, 95% CI 1.03-3.61, p = 0.04), age (HR 1.04, 95% CI 1.01-1.08, p = 0.02), stage (HR 3.67, 95% CI 1.13-11.92, p = 0.03), residual tumor > 1 cm (HR 3.79, 95% CI 1.61-8.95, p < 0.01), and lymph node metastasis (HR 2.46, 95% CI 1.27-4.78, p < 0.01) were independent risk factors for recurrence. CONCLUSION: This study showed positive association between relatively high level of ionized calcium level and recurrence risk of EOC. High normocalcemia showed the potential as a biomarker for prognosis of EOC.

Predicting Cyanobacterial Blooms Using Hyperspectral Images in a Regulated River.

Process-based modeling for predicting harmful cyanobacteria is affected by a variety of factors, including the initial conditions, boundary conditions (tributary inflows and atmosphere), and mechanisms related to cyanobacteria growth and death. While the initial conditions do not significantly affect long-term predictions, the initial cyanobacterial distribution in water is particularly important for short-term predictions. Point-based observation data have typically been used for cyanobacteria prediction of initial conditions. These initial conditions are determined through the linear interpolation of point-based observation data and may differ from the actual cyanobacteria distribution. This study presents an optimal method of applying hyperspectral images to establish the Environmental Fluid Dynamics Code-National Institute of Environment Research (EFDC-NIER) model initial conditions. Utilizing hyperspectral images to determine the EFDC-NIER model initial conditions involves four steps that are performed sequentially and automated in MATLAB. The EFDC-NIER model is established using three grid resolution cases for the Changnyeong-Haman weir section of the Nakdong River Basin, where Microcystis dominates during the summer (July to September). The effects of grid resolution on (1) water quality modeling and (2) initial conditions determined using cumulative distribution functions are evaluated. Additionally, the differences in Microcystis values are compared when applying initial conditions using hyperspectral images and point-based evaluation data. Hyperspectral images allow detailed initial conditions to be applied in the EFDC-NIER model based on the plane-unit cyanobacterial information observed in grids, which can reduce uncertainties in water quality (cyanobacteria) modeling.

The Effectiveness of Anti-Apoptotic Agents to Preserve Primordial Follicles and Prevent Tissue Damage during Ovarian Tissue Cryopreservation and Xenotransplantation.

The purpose of this study is to investigate the effectiveness of sphingosine-1-phosphate (S1P) and Z-VAD-FMK (Z-VAD) as anti-apoptotic agents to preserve ovarian function and prevent tissue damage during ovarian tissue cryopreservation and transplantation. This study consisted of two steps, in vitro and in vivo. In the first step, human ovarian tissues were cryopreserved using slow-freezing media alone, S1P, or Z-VAD (control, S1P, Z-VAD group); based on the outcomes in these groups, Z-VAD was selected for subsequent xenotransplantation. In the second step, human frozen/thawed ovarian tissues were grafted into fifty mice divided into three groups: slow-freezing/thawing and transplantation without an anti-apoptotic agent (Trans-control) and xenotransplantation with or without Z-VAD injection (Trans-Z-VAD-positive and Trams-Z-VAD-negative groups, respectively). In the first step, the Z-VAD group had a significantly higher primordial follicular count than the S1P (p = 0.005) and control groups (p = 0.04). Transplanted ovarian tissues were obtained 4 weeks after transplantation (second step). Angiogenesis was significantly increased in the Z-VAD-negative (p = 0.03) and -positive (p = 0.04) groups compared to the control group. This study demonstrated that slow-freezing and transplantation with Z-VAD is an effective method for preserving primordial follicle counts, decreasing double-strand DNA breaks, and increasing angiogenesis in a mouse model. Further molecular and clinical studies are needed to confirm these results.

Pembrolizumab plus GX-188E therapeutic DNA vaccine in patients with HPV-16-positive or HPV-18-positive advanced cervical cancer: interim results of a single-arm, phase 2 trial.

BACKGROUND: Survival outcomes for patients with recurrent or advanced cervical cancer are poor. Pembrolizumab has been approved for the treatment of recurrent or metastatic cervical cancer, with an overall response rate of 14·3%. GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6-specific and E7-specific T-cell responses and cervical lesion regression in patients with cervical precancer. We aimed to investigate whether a combination of GX-188E therapeutic DNA vaccine plus pembrolizumab showed antitumour activity against recurrent or advanced cervical cancer. METHODS: In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced, inoperable cervical cancer, who were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically confirmed recurrent or advanced HPV-positive (HPV-16 or HPV-18) cervical cancer, and who had progressed after available standard-of-care therapy were recruited from seven hospitals in South Korea. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, and 19, with one optional dose at week 46 that was at the investigator's discretion, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the overall response rate within 24 weeks assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 in patients who received at least 45 days of treatment 45 days of treatment with at least one post-baseline tumour assessment, and this is the report of a planned interim analysis. This trial is registered with ClinicalTrials.gov, NCT03444376. FINDINGS: Between June 19, 2018, and March 20, 2020, 36 patients were enrolled and received at least one dose of the study treatment. 26 patients were evaluable for interim activity assessment, with at least one post-baseline tumour assessment at week 10. At the data cutoff date on March 30, 2020, median follow-up duration was 6·2 months (IQR 3·5-8·1). At 24 weeks, 11 (42%; 95% CI 23-63) of 26 patients achieved an overall response; four (15%) had a complete response and seven (27%) had a partial response. 16 (44%) of 36 patients had treatment-related adverse events of any grade and four (11%) had grade 3-4 treatment-related adverse events. Grade 3 increased aspartate aminotransferase, syncope, pericardial effusion, and hyperkalaemia, and grade 4 increased alanine aminotransferase were reported in one patient each. No treatment-related deaths were reported. INTERPRETATION: Treatment with GX-188E therapeutic vaccine plus pembrolizumab for patients with recurrent or advanced cervical cancer was safe and treatment-related adverse events were manageable. This combination therapy showed preliminary antitumour activity in this interim analysis, which could represent a new potential treatment option for this patient population. This trial is ongoing. FUNDING: National OncoVenture.

The impact of previous cesarean section (C/S) on the risk for post-molar gestational trophoblastic neoplasia (GTN).

OBJECTIVE: To investigate the relationship between previous cesarean section (C/S) and risk for post-molar gestational trophoblastic neoplasia (GTN). METHODS: Data from patients who were treated for hydatidiform moles between 1995 and 2016 were retrospectively reviewed. Patient age, gravidity, parity, abortion history, gestational age, pretreatment beta-human chorionic gonadotropin (HCG), previous molar pregnancy, clinical symptoms, enlarged uterus, theca lutein cyst, type of GTN, World Health Organization risk score, chemotherapy, and mode of delivery were recorded. Hazard ratios (HR) and 95% confidence intervals (CI) for variables associated with the occurrence of post-molar GTN and invasive mole were estimated by univariate and multivariate Cox proportional hazards models. RESULTS: From 1995 to 2016, 182 patients were diagnosed with molar pregnancy and underwent treatment. Patients with previous C/S (C/S group) had higher age (37.0 vs 32.8. p = 0.004), gravidity (3.1 vs 2.0, p < 0.001), and parity (1.6 vs 0.9, p < 0.001) than patients without previous C/S (non-C/S group). Post-molar GTN (43.5 vs 26.5%, p < 0.001), invasive mole (21.7 vs 3.7%, p < 0.001), hysterectomy (28.3 vs 6.6%, p < 0.001), and chemotherapy (45.7 vs 28.7%, p = 0.03) were more frequent in the C/S group. In multivariate analysis, independent risk factors for post-molar GTN were previous C/S (HR 5.1, 95% CI 2.1-12.7), abortion history (HR 6.3, 95% CI 2.5-15.6), and pretreatment ß-hCG (HR 1.3, 95% CI 1.1-1.6). CONCLUSIONS: In this study, C/S was a strong risk factor for occurrence of post-molar GTN and invasive mole. Aggressive treatment, such as multi-agent chemotherapy or hysterectomy, can be considered for hydatidiform moles in patients with a C/S history.

Learning curve for sentinel lymph node mapping in gynecologic malignancies.

BACKGROUND AND OBJECTIVES: Only a few studies have reported the learning curve for sentinel lymph node (SLN) detection in gynecologic malignancies. We investigated the learning curve for SLN detection during robot-assisted laparoscopic surgery for endometrial and cervical carcinomas. METHODS: This retrospective analysis included patients with stage IA to IIA1 cervical cancer or stage I to III endometrial cancer who underwent SLN mapping using indocyanine green during robot-assisted laparoscopic surgery performed by a single surgeon. Learning curves were analyzed in consecutive cases using SLN detection rates and the cumulative sum (CUSUM) method. RESULTS: SLN mapping was achieved in 81.25% (65/80), 77.50% (62/80), and 66.25% (53/80) of the cases involving the right, left, and simultaneous bilateral pelvic areas, respectively. Learning curve analysis based on the cumulative detection rate showed initial fluctuations followed by stabilization; the time required for proficiency was discordant among the LN regions. However, the CUSUM method showed proficient mapping of the right, left, and bilateral SLNs after 27 to 28 cases. CONCLUSION: At least 27 cases were required for SLN mapping proficiency in gynecologic cancer; the learning period could influence the surgical quality. Further studies are warranted to confirm the impact of this learning curve on disease outcomes.

Development of water quality criteria for arsenic to protect aquatic life based on species sensitivity distribution.

Arsenic is a hazardous environmental pollutant widely distributed globally. Arsenic toxicity is well known and it is regulated by many countries in terms of managing water quality and protecting aquatic organisms. Unfortunately, water quality criterion (WQC) to protect aquatic organisms has not been introduced in Korea yet. Thus, it is of great importance and necessity to introduce WQC to protect aquatic organisms from arsenic, as WQC play a significant role in protecting aquatic ecosystems from pollutants. Therefore, the purpose of this study is to derive arsenic water quality criterion for aquatic life in Korea. Arsenic acute toxicity tests were performed with 10 Korean native aquatic species, which belong to 7 different taxonomic groups. Based on the results of acute toxicity test and additional toxicity data from literature, the species sensitivity distribution (SSD) method was used in ecological risk assessment. The arsenic concentration of 95% protection level for aquatic life was 0.229 mg L-1 in this study. An assessment factor 3 and a background concentration 0.0004 mg L-1 were applied to the concentration value in consideration of the uncertainty of the data and the amount of arsenic natural generation. Consequently, the WQC value derived for arsenic was found to be 0.077 mg L-1. These results will serve as reference values to establish water quality criterion for the protection of aquatic life in Korea.

Advances in the Treatment and Prevention of Chemotherapy-Induced Ovarian Toxicity.

Due to improvements in chemotherapeutic agents, cancer treatment efficacy and cancer patient survival rates have greatly improved, but unfortunately gonadal damage remains a major complication. Gonadotoxic chemotherapy, including alkylating agents during reproductive age, can lead to iatrogenic premature ovarian insufficiency (POI), and loss of fertility. In recent years, the demand for fertility preservation has increased dramatically among female cancer patients. Currently, embryo and oocyte cryopreservation are the only established options for fertility preservation in women. However, there is growing evidence for other experimental techniques including ovarian tissue cryopreservation, oocyte in vitro maturation, artificial ovaries, stem cell technologies, and ovarian suppression. To prevent fertility loss in women with cancer, individualized fertility preservation options including established and experimental techniques that take into consideration the patient's age, marital status, chemotherapy regimen, and the possibility of treatment delay should be provided. In addition, effective multidisciplinary oncofertility strategies that involve a highly skilled and experienced oncofertility team consisting of medical oncologists, gynecologists, reproductive biologists, surgical oncologists, patient care coordinators, and research scientists are necessary to provide cancer patients with high-quality care.

Doctor and patient awareness of treatment options for cervical intraepithelial neoplasia 1 (CIN 1): a survey questionnaire approach.

The purpose of this study was to investigate doctors' and patients' perceptions of cervical intraepithelial neoplasia 1 (CIN 1) and its treatment methods. A survey questionnaire was offered to obstetrics and gynaecology doctors and patients with CIN 1 in 2017. Only 43% of patients knew of this disease. Regarding perceptions of its aetiology, 64% of the patients perceived human papillomavirus infection to be the main cause of CIN 1. Patients' most preferred treatments were medication (20%), followed by alternative treatment (14%). Among doctors, regular follow-up was the most preferred method for managing CIN 1. The survey showed that current treatment modalities for CIN 1 were satisfactory to only half of doctors (50%) and patients (53%). Overall, 70% of doctors responded that new drug development for CIN 1 is needed. Although, CIN 1 is a low-grade lesion, doctors and patients expressed the desire for new therapeutic agents to manage it.IMPACT STATEMENTWhat is already known on this subject? In general, treatment is not recommended for CIN 1 because lesions are considered indicative of transient HPV infection and spontaneously regress in most patients.What do the results of this study add? Regular follow-up for CIN 1 were satisfactory to only half of doctors and patients. Thirty-six percent of patients wanted active treatment instead of regular follow-up. In addition, 70% of doctors responded that new drug development for CIN 1 is needed.What are the implications of these findings for clinical practice and/or further research? Our results support the need for therapeutic agents for CIN 1.

Prevalence of human papillomavirus-related diseases in the Republic of Korea: a cross-sectional study.

OBJECTIVE: We aimed to evaluate trends in the prevalence of human papillomavirus (HPV)-related diseases in the era before the introduction of organised HPV vaccination programmes in the Republic of Korea. METHODS: This cross-sectional study used National Health Insurance Service data from 2002 to 2015 and included participants who were diagnosed with the following HPV-related diseases (codes from the International Classification of Diseases, 10th Revision): genital warts (A63.0); cancer in the head and neck (C00-C10), anus (C21), vulva (C51), vagina (C52), cervix uteri (C53) and penis (C60); carcinoma in situ (CIS) of the lip/oral cavity/pharynx (D00.0), anus (D01.3), cervix (D06), vulva (D07.1), vagina (D07.2) and penis (D07.4); benign neoplasms of the larynx (D14.1); and dysplasia of the cervix (N87), vagina (N89) and vulva (N90). For each diagnosis, the fraction of cases attributable to HPV in Korea was assessed based on the percentages of diseases attributable to HPV reported in some international studies. The age-standardised prevalence was estimated using the direct population-based method. RESULTS: The overall age-standardised prevalence of HPV-related diseases increased from 2002 to 2015, mainly due to increased prevalence of genital warts in men and cervical dysplasia and CIS in women. In women, genital wart prevalence increased from 2002 (24.4 per 100 000) to 2011 (57.1) and then decreased until 2015 (53.5); in men, the prevalence increased steadily from 2002 (22.9) to 2015 (109.4). The prevalence of cervical dysplasia and CIS increased (from 86.5 in 2002 to 484.5 in 2015, and from 60.3 in 2002 to 114.9 in 2015, respectively), but that of cervical cancer decreased (from 120.0 in 2002 to 106.9 in 2015). CONCLUSIONS: Non-organised HPV vaccination and organised cervical cancer screening may have contributed to the downward trend in genital wart prevalence and the upward trend in cervical abnormalities among women.

CXC chemokine ligand 1 mediates adiponectin-induced angiogenesis in ovarian cancer.

OBJECTIVES: Adiponectin is a cytokine secreted from adipose tissue that regulates energy homeostasis, inflammation, and cell proliferation. Obesity is associated with increased risk of various cancers, including ovarian cancer. Adipokines, including adiponectin, have been implicated as a factor linking obesity and carcinogenesis. The oncogenic role of adiponectin is not known with regard to various cancer types. We sought to determine the role of adiponectin in angiogenesis in ovarian cancer in vitro. METHODS: We transfected SKOV3 cells with vascular endothelial growth factor small interfering RNA in order to identify the independent angiogenic role of adiponectin in ovarian cancer. The vascular endothelial growth factor knockdown SKOV3 cell lines were treated with adiponectin for 48 h. The cytokines involved in adiponectin-mediated angiogenesis were explored using the human angiogenesis cytokine array and were verified with the enzyme-linked immunosorbent assay. The angiogenic effect of adiponectin was evaluated using the human umbilical vein endothelial cell tube formation assay. We also investigated the effects of adiponectin treatment on the migration and invasion of SKOV3 cells. RESULTS: The number of tubes formed by human umbilical vein endothelial cell decreased significantly after knockdown of vascular endothelial growth factor (via transfection of vascular endothelial growth factor small interfering RNA into SKOV3 cells). When these vascular endothelial growth factor knockdown SKOV3 cells were treated with adiponectin, there was an increase in the number of tubes in a tube formation assay. Following adiponectin treatment, the CXC chemokine ligand 1 secretion increased in a cytokine array. This was confirmed by both enzyme-linked immunosorbent assay and Western blot. The increased secretion of CXC chemokine ligand 1 by adiponectin occurred regardless of vascular endothelial growth factor knockdown. In addition, the induction of migration and invasion of SKOV3 cells were significantly stronger with adiponectin treatment than they were without. CONCLUSION: Adiponectin treatment of ovarian cancer cells induces angiogenesis via CXC chemokine ligand 1 independently of vascular endothelial growth factor. These findings suggest that adiponectin may serve as a novel therapeutic target for ovarian cancer.

Porous TiO2 Nanotube Arrays for Drug Loading and Their Elution Sensing.

Porous TiO2 nanotube arrays have been attracting much attention as optical sensing layers and surface layers of dental implants because they are stable in acid and biocompatible. To use them as the optical sensing layers, TiO2 nanotube arrays with various structures were fabricated and obtained an optimized microstructure at 50 V, 50 min and 0.5 wt% of NH4F, 7.4 vol% deionized water in ethylene glycol. TiO2 nanotube arrays which had diameters of ~73.54 nm and lengths of ~3.39 µm showed the best sensing performance. A Ti implant was also anodized at 60 V for 4 hr in an ethylene glycol electrolyte and TiO2 nanotube arrays showed the pore diameter of 156.01 nm and the thickness of 6.87 µm. Recombinant human bone morphogenetic protein-2 (rhBMP-2), isobutylphenyl propionic acid, and sodium alendronate were loaded into the TiO2 nanotube arrays on the surface of the Ti implant. For elution of these drugs, optical thickness changes of 2.4 nm, 3.5 nm and 3.1 nm were respectively observed for about 2.2 hr, 3.6 hr and 3.1 hr. The TiO2 nanotube arrays were useful for drug loading and their elution interferometric sensing.

Association Between Passive Smoking and the Risk of Cervical Intraepithelial Neoplasia 1 in Korean Women.

BACKGROUND: The role of passive smoking on cervical carcinogenesis remains controversial. We investigated the association of passive smoking with the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: The study recruited 1,322 women, aged 18-65 with normal cytology (n = 592), CIN1 (n = 420), CIN2/3 (n = 165), and cervical cancer (n = 145) from 2006 to 2009. This study is a cross-sectional analysis using the baseline data from the Korean human papillomavirus (HPV) cohort study. Detailed information on smoking behaviors and lifestyles were collected using questionnaires. Multinomial logistic regression analysis was performed to estimate multivariable-adjusted odds ratios (ORs). RESULTS: Passive smoking was not statistically related to the risk of CINs and cervical cancer. However, passive smoking among non-smokers was associated with higher CIN 1 risk (OR 1.53; 95% confidence interval [CI], 1.07-2.18), compared to not passive smoking, after adjusting for demographic factors, lifestyles, and oncogenic-HPV infection status. CIN 1 risk increased with longer time exposed to passive smoking (P for trend <0.0003). Multivariate odds of <2 hours/day of passive smoking and that of ≥2 hours/day of passive smoking were 2.48 (95% CI, 1.49-4.14) and 2.28 (95% CI, 1.21-4.26) for CIN 1, compared to not passive smoking. CONCLUSIONS: This study found that passive smoking among non-smoking women is associated with the risk of CIN 1.