Optimal Dietary Intake of Riboflavin Associated with Lower Risk of Cervical Cancer in Korea: Korean National Health and Nutrition Examination Survey 2010-2021.

BACKGROUND: This study aimed to evaluate the association between the dietary intake of vitamin B complex (thiamine, riboflavin, and niacin) and cervical cancer in Korea. METHODS: The data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2021 were analyzed, which included 28,306 participants who were categorized into non-cervical cancer and cervical cancer groups. The following dietary intake threshold levels of thiamine, riboflavin, and niacin were identified based on the recommended daily allowances (RDAs): thiamine, 1.1 mg/day; riboflavin, 1.2 mg/day; and niacin, 14 mg/day. RESULTS: Among 28,306 participants, 27,976 were in the non-cervical cancer group and 330 were in the cervical cancer group. Riboflavin intakes of more than 1.2 mg/day but less than 2.4 mg/day were associated with a significantly reduced risk of cervical cancer, whereas intakes of above 2.4 mg/day were not associated with cervical cancer. Thiamine and niacin intakes were not significantly related to the risk of cervical cancer. CONCLUSIONS: The results of this study suggest that an intake of riboflavin of 1.2-2.4 mg/day may contribute to a lower risk of cervical cancer.

Assessing the New 2020 ESGO/ESTRO/ESP Endometrial Cancer Risk Molecular Categorization System for Predicting Survival and Recurrence.

This study aimed to evaluate the efficacy of the 2020 European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines for endometrial cancer (EC). Additionally, a novel risk category incorporating clinicopathological and molecular factors was introduced. The predictive value of this new category for recurrence and survival in Korean patients with EC was assessed, and comparisons were made with the 2013 and 2016 European Society of Medical Oncology (ESMO) risk classifications. Patients with EC were categorized into the POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), p53-aberrant (P53abn), and nonspecific molecular profile (NSMP) subtypes. Recurrence, survival, and adjuvant therapy were assessed according to each classification. Notably, patients with the POLEmut subtype showed no relapse, while patients with the P53abn subtype exhibited higher recurrence (31.8%) and mortality rates (31.8%). Regarding adjuvant therapy, 33.3% of low-risk patients were overtreated according to the 2020 ESGO/ESTRO/ESP guidelines. Overall and progression-free survival differed significantly across molecular classifications, with the POLEmut subtype showing the best and the P53abn subtype showing the worst outcomes. The 2020 ESGO molecular classification system demonstrated practical utility and significantly influenced survival outcomes. Immunohistochemistry for TP53 and MMR, along with POLE sequencing, facilitated substantial patient reclassification, underscoring the clinical relevance of molecular risk categories in EC management.

Menopausal status induces vaginal dysbiosis in women with human papillomavirus infection.

In this study, we examined the difference in the vaginal microbiota of women infected with human papillomavirus (HPV), according to menopausal status. A total of 75 cervicovaginal swab samples from 38 pre- and 37 postmenopausal women with HPV infection were obtained from the Korean HPV cohort. Vaginal microbiota analysis, including microbial diversity and specific bacterial abundances, was performed using 16S rRNA gene sequencing. The mean age of the pre- and postmenopausal women were 29.5 and 55.8 years, respectively (p < 0.0001). Lactobacillus spp. were predominant in both groups; however, a marked decrease was observed in postmenopausal women compared to premenopausal women (44.3% vs. 74.2%). Various anaerobic bacteria also showed a relatively high abundance in the postmenopausal group; Atopobium vagina and Gardnerella vaginalis significantly increased in postmenopausal women. Interestingly, no significant differences in bacterial richness were observed between the two groups. However, significant differences in beta-diversity were observed using the Bray-Curtis (p = 0.001), Generalized UniFrac (p = 0.002), Jensen-Shannon (p = 0.001), and UniFrac algorithms (p = 0.002). Theres results indicate that postmenopausal women with HPV infection exhibited a higher degree of vaginal dysbiosis than premenopausal women. Further, HPV-infected postmenopausal women had increased vaginal microbial diversity, characterized by an increase in anaerobic bacteria and concomitant depletion of Lactobacillus spp.

A phase 1/2a, dose-escalation, safety, and preliminary efficacy study of the RKP00156 vaginal tablet in healthy women and patients with cervical intraepithelial neoplasia 2.

OBJECTIVE: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). METHODS: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women. In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. RESULTS: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (-98.61%; 95% confidence interval=-99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. CONCLUSION: The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02139267.

Development and validation of artificial intelligence-based analysis software to support screening system of cervical intraepithelial neoplasia.

Cervical cancer, the fourth most common cancer among women worldwide, often proves fatal and stems from precursor lesions caused by high-risk human papillomavirus (HR-HPV) infection. Accurate and early diagnosis is crucial for effective treatment. Current screening methods, such as the Pap test, liquid-based cytology (LBC), visual inspection with acetic acid (VIA), and HPV DNA testing, have limitations, requiring confirmation through colposcopy. This study introduces CerviCARE AI, an artificial intelligence (AI) analysis software, to address colposcopy challenges. It automatically analyzes Tele-cervicography images, distinguishing between low-grade and high-grade lesions. In a multicenter retrospective study, CerviCARE AI achieved a remarkable sensitivity of 98% for high-risk groups (P2, P3, HSIL or higher, CIN2 or higher) and a specificity of 95.5%. These findings underscore CerviCARE AI's potential as a valuable diagnostic tool for highly accurate identification of cervical precancerous lesions. While further prospective research is needed to validate its clinical utility, this AI system holds promise for improving cervical cancer screening and lessening the burden of this deadly disease.

Short-term Impact of Hormone Replacement Therapy on Risk of Breast Cancer in BRCA Mutation Carriers: A Nationwide Study in South Korea.

PURPOSE: BRCA1/2 mutations are well-known risk factors for breast and ovarian cancers in women. Risk-reducing salpingo-oophorectomy (RRSO) is the standard treatment for preventing ovarian cancer with BRCA mutations. Postmenopausal syndrome (symptoms after RRSO can be alleviated by hormone replacement therapy (HRT); however, the use of HRT in carriers of BRCA mutations has been controversial because of the concern that HRT increases the risk of breast cancer. This study aimed to evaluate the effects of HRT in BRCA mutation carriers who underwent RRSO. MATERIALS AND METHODS: A total of 151 carriers, who underwent RRSO between 2013 and 2020 after the diagnosis of BRCA1 or BRCA2 mutations were selected and followed up for a median of 3.03 years. Patients were divided into two groups: those who received HRT after RRSO (n=33) and those who did not (n=118). We compared the incidence of breast cancer over time between these two groups. RESULTS: There was no significant difference in the incidence of breast cancer between women who received HRT and those who did not (p=0.229). Multivariate logistic regression analysis, adjusted for age and parity revealed no significant difference in the risk of breast cancer between these two groups (hazard ratio, 0.312; 95% confidence interval, 0.039 to 2.480; p=0.278). CONCLUSION: In this study, we found no relationship between post-RRSO HRT and breast cancer in the population with BRCA mutations. Therefore, healthcare providers may consider the alleviation of symptoms of postmenopausal syndrome through HRT in patients who underwent RRSO.

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).

Depressed Mood as a Significant Risk Factor for Gynecological Cancer Aggravation.

BACKGROUND: The aim of this study was to evaluate the relationship between depressed mood and gynecological cancer outcomes, identifying risk factors for cancer aggravation. METHODS: This study was a retrospective analysis of gynecological cancer patients (January 2020-August 2022) at Korea University Anam Hospital using Patient Health Questionnaire-9 (PHQ-9). Patients were classified into non-depressed mood (NDM)- and depressed mood (DM)-based scores. Statistical analysis was performed using Student's t-test, chi-square test, Fisher's exact test, Kaplan-Meier analysis, and Cox regression analyzing using SPSS. RESULTS: Of the 217 participants, the NDM group comprised 129 patients, and the DM group comprised 88. The two-year disease-free survival (DFS) rates showed significant differences (NDM, 93.6%; DM 86.4%; p = 0.006), but overall survival (OS) did not (p = 0.128). Patients with stage 3 or higher cancer, undergoing five or more chemotherapies, experiencing post-chemotherapy side effects, and depressed mood had an increased risk of cancer aggravation. CONCLUSIONS: Appropriate treatment of depressed mood, as well as adequate treatment for advanced gynecological cancer patients, those with numerous CTx., and those with post-CTx. side effects, may contribute to reducing the risk of cancer aggravation.

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.

Pivotal Clinical Study to Evaluate the Efficacy and Safety of Assistive Artificial Intelligence-Based Software for Cervical Cancer Diagnosis.

Colposcopy is the gold standard diagnostic tool for identifying cervical lesions. However, the accuracy of colposcopies depends on the proficiency of the colposcopist. Machine learning algorithms using an artificial intelligence (AI) system can quickly process large amounts of data and have been successfully applied in several clinical situations. This study evaluated the feasibility of an AI system as an assistive tool for diagnosing high-grade cervical intraepithelial neoplasia lesions compared to the human interpretation of cervical images. This two-centered, crossover, double-blind, randomized controlled trial included 886 randomly selected images. Four colposcopists (two proficient and two inexperienced) independently evaluated cervical images, once with and the other time without the aid of the Cerviray AI® system (AIDOT, Seoul, Republic of Korea). The AI aid demonstrated improved areas under the curve on the localization receiver-operating characteristic curve compared with the colposcopy impressions of colposcopists (difference 0.12, 95% confidence interval, 0.10-0.14, p < 0.001). Sensitivity and specificity also improved when using the AI system (89.18% vs. 71.33%; p < 0.001, 96.68% vs. 92.16%; p < 0.001, respectively). Additionally, the classification accuracy rate improved with the aid of AI (86.40% vs. 75.45%; p < 0.001). Overall, the AI system could be used as an assistive diagnostic tool for both proficient and inexperienced colposcopists in cervical cancer screenings to estimate the impression and location of pathologic lesions. Further utilization of this system could help inexperienced colposcopists confirm where to perform a biopsy to diagnose high-grade lesions.

Unique inverse association between allergic rhinitis and periodontitis: a nationwide population-based study.

The increase in fine dust levels in the atmosphere has been associated with a growth in the incidence of environmental diseases, including allergic rhinitis (AR). Nasal obstruction caused by AR can impact the conditions in the oral cavity. The aim of this study was to determine the association between AR and periodontitis in the Republic of Korea. This study was based on data from the Seventh Korea National Health and Nutrition Examination Survey (KNHANES VII-1, 2016), which was conducted by the Korea Centers for Disease Control and Prevention. The study included 6129 adults older than 19 years. Sociodemographic information and medical variables including history of treatment of periodontitis (HTP) reflecting diagnosis of periodontitis and diagnosis of diseases such as AR were extracted from the data. HTP and AR were reported for 22.81 ± 0.84% (weighted percentage ± standard error) and 15.32 ± 0.63% of the studied population, respectively. A diagnosis of AR was reported for 11.07 ± 1.28% of those with HTP and for 17.55 ± 1.84% of those without HTP. From these, it was inferred that the prevalence of HTP was 1.536-fold higher in the non-AR group than in their counterparts with AR. Significant association was found between AR and HTP among those aged ≤ 64 years and the odds ratio (OR) of AR group for HTP was 0.62 (95% confidence interval:0.44-0.87; P = 0.0057). From this result, it can be inferred that patients diagnosed AR have lower risk of periodontitis.

Effect of photodynamic therapy according to differences in photosensitizers on Staphylococcus aureus biofilm on titanium.

PURPOSE: This study aimed to evaluate the antimicrobial effect of photodynamic therapy (PDT) against Staphylococcus aureus biofilm on a titanium surface and to compare the differences in the effect of PDT using toluidine blue O (TBO) and methylene blue (MB) as a photosensitizer. METHODS: The bacterial strain S. aureus ATCC 25,923 was used. Sandblasted and acid-etched (SLA) disks were divided into the following six groups: phosphate buffer saline (PBS), TBO, MB, PBS with laser (PBS + L), TBO with laser (TBO + L), and MB with laser (MB + L). The laser group samples were irradiated by a cold diode laser for 60 s. After treatment, the number of surviving bacteria was calculated by counting the colony-forming units (CFUs) and confocal laser scanning microscopy (CLSM) was applied to observe the bacteria on the disk surface. RESULTS: The TBO + L and MB + L groups showed significantly lower CFU/ml than the other groups (p < 0.01). The TBO + L group showed significantly lower CFU/ml than the MB + L group (p = 0.032). There was no significant difference between the PBS, TBO, MB, and PBS + L groups. Within the limitations of this in vitro study, PDT with TBO and MB can effectively reduce S. aureus biofilm on SLA titanium surfaces. TBO is more effective than MB as a photosensitizer. PDT with TBO may be applied to the treatment of peri­implant disease in the future.

Comparison of Surgical Outcomes between Single-Port Laparoscopic Surgery and Da Vinci Single-Port Robotic Surgery.

BACKGROUND: The aim of this study is to compare the surgical outcomes of single-port laparoscopic surgery (SPLS) and single-port robotic surgery (SPRS). METHODS: We retrospectively analyzed patients who underwent a hysterectomy, ovarian cystectomy, or myomectomy with SPLS or SPRS from January 2020 to July 2022. Statistical analyses were performed using the SPSS chi-square test and student's t-test. RESULTS: A total of 566 surgeries including single-port laparoscopic hysterectomy (SPLH; n = 148), single-port robotic hysterectomy (SPRH; n = 35), single-port laparoscopic ovarian cystectomy (SPLC; n = 207), single-port robotic ovarian cystectomy (SPRC; n = 108), single-port laparoscopic myomectomy (SPLM; n = 12), and single-port robotic myomectomy (SPRM; n = 56). The SPRH, SPRC, and SPRM groups had a shorter operation time than the SPLS group, although the results were not statistically significant (SPRH vs. SPLH, p = 0.134; SPRC vs. SPLC, p = 0.098; SPRM vs. SPLM, p = 0.202). Incisional hernia occurred as a postoperative complication in two patients only in the SPLH group. Postoperative Hb changes were lower in the SPRC and SPRM groups than in the SPLC and SPLM groups (SPRC vs. SPLC, p = 0.023; SPRM vs. SPLM, p = 0.010). CONCLUSIONS: Our study demonstrated that the SPRS had comparable surgical outcomes when compared to the SPLS. Therefore, the SPRS should be considered a feasible and safe option for gynecologic patients.

Trends in Gynecologic Carcinosarcoma Based on Analysis of the Surveillance Epidemiology End Result (SEER) Database.

Carcinosarcomas (malignant mixed Mullerian tumors) of a female genital organ are rare tumors associated with a poor survival. The purpose of this study was to identify site-specific differences in the incidence and prognosis in carcinosarcomas originating in the uterus, cervix, or ovary. The data of patients with gynecologic carcinosarcomas were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2016. The characteristics of gynecologic carcinosarcomas were compared using Pearson X2 and Fisher's exact tests. Kaplan-Meier models were used for cause-specific survival (CSS) analysis. The cohort included 7086 females, including 5731 cases of uterine carcinosarcoma, 161 cervical carcinosarcomas, and 1193 ovarian carcinosarcomas. The age-adjusted incidence rates of uterine, cervical, and ovarian carcinosarcoma were 3.9, 0.1, and 0.6 per 1,000,000, respectively. In the distribution of carcinosarcoma incidence by race, compared with the uterus or cervix, those originating from the ovary were unequally distributed in Caucasians (84.4% versus 69.6%, 67.7%; p < 0.001). The incidence of uterine carcinosarcoma steadily increased over time, from 2.2 in 2000 to 5.5 in 2016 (per 1,000,000), while cervical or ovarian carcinosarcoma showed no significant difference in incidence. The five-year CSS rates based on the site of origin (uterus, cervix, and ovary) were 39.9%, 33.1%, and 25.8%, respectively. The incidence rates of gynecologic carcinosarcoma, especially uterine carcinosarcoma, are gradually increasing. Although uterine carcinosarcoma is associated with a higher incidence than the others, it has a better prognosis compared with ovarian and cervical carcinosarcoma. The survival rates were worst in ovarian carcinosarcoma.

Parental Factors Affecting Decision to Vaccinate Their Daughters against Human Papillomavirus.

ABSTRACT: Human papillomavirus (HPV) vaccination was introduced in the National Immunization Program (NIP) in Korea targeting girls aged 12 years to receive two doses of HPV vaccine to prevent cervical cancer. This study aimed to evaluate the factors that may influence parental decision to inoculate their daughters in Korea. A cross-sectional survey was conducted in 2020 by interviewing the parents of 2,000 nationally representative girls eligible for HPV NIP. By the daughters' status of HPV vaccination, the probabilities for each variable were compared with evaluate the factors that could affect parents' decision to inoculate their daughters with HPV vaccines. Compared with parents who were not vaccinated with HPV, parents who were vaccinated with HPV were 2.40 times more likely to decide to vaccinate their daughters with HPV. Parents who regularly undergo cervical cancer screening were 1.39 times more likely to decide to vaccinate their daughters with HPV than parents who do not receive regular checkups. Parents' perceived knowledge and perceived risk had a significant impact on their decision to vaccinate their daughters with HPV vaccines. Parents who had strong belief that HPV vaccine is safe in terms of adverse effects were 10 times more likely to decide to vaccinate their daughters against HPV. Parental factors including HPV-related health behavior and awareness were found to be associated with parental decision to vaccinate their daughters against HPV. To improve HPV vaccine uptake at 12 years, it is required to improve parental awareness on HPV through public communication supported by scientific-based evidence. PREVENTION RELEVANCE: Parental HPV vaccination and maternal regular cervical cancer screening were positively associated with parental decision to vaccinate their daughters against HPV. Parents' perceived knowledge of HPV vaccination and perceived risk of cervical cancer play an important role in determining whether their 12-year-old daughters will be vaccinated against HPV.

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.

Lymphocyte activation gene (LAG)-3 is a potential immunotherapeutic target for microsatellite stable, programmed death-ligand 1 (PD-L1)-positive endometrioid endometrial cancer.

OBJECTIVE: Immune checkpoint inhibitors have been widely used in the treatment of endometrial cancer (EC) with microsatellite instability-hypermutated (MSI-H). However, there is an unmet need for microsatellite stable (MSS) EC because of their modest activity. This study aimed to identify potential immune-related biomarkers in MSS EC. METHODS: One hundred and twenty-three patients with EC who underwent hysterectomy were enrolled. MSI status was determined using MSI analysis and/or immunohistochemical staining for mismatch repair proteins. Immunohistochemical analysis of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), PD-L2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), cluster of differentiation 3 (CD3), CD8, lymphocyte activation gene-3 (LAG-3), indoleamine 2,3-dioxygenase 1 (IDO1), phosphatase and tensin homolog (PTEN), p53, AT-rich interactive domain-containing protein 1A (ARID1A), and ß-catenin was performed using tissue microarray blocks. RESULTS: Among 123 patients, 95 (77.2%) were classified as having MSS. Within EC with MSS, PD-L1 positivity was significantly associated with positive PD-1 (p<0.001), CTLA-4 (p<0.001), CD3 (p=0.002), CD8 (p<0.001), and LAG-3 (p<0.001). In the univariate analysis, positive PD-1 (odds ratio [OR]=9.281; 95% confidence interval [CI]=2.560-33.653; p<0.001), CTLA-4 (OR=5.33; 95% CI=1.418-19.307; p=0.005), CD3 (OR=5.571; 95% CI=1.746-17.775; p=0.004), CD8 (OR=6.909; 95% CI=2.647-18.037; p<0.001), and LAG-3 (OR=9.75; 95% CI=1.947-48.828; p=0.005) were significantly associated with PD-L1 positivity in MSS EC. In the multivariate analysis, LAG-3 demonstrated a significant association with positive PD-L1 expression in MSS EC (OR=5.061; 95% CI=1.534-16.693; p=0.023). CONCLUSION: In patients with MSS EC harboring PD-L1, LAG-3 may be a potential immunotherapeutic target. Clinical trials investigating the role of anti-LAG-3 antibodies, alone or in combination with other immunotherapies, are warranted.

Prognostic value of textural features obtained from F-fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) in patients with locally advanced cervical cancer undergoing concurrent chemoradiotherapy.

OBJECTIVE: To evaluate whether textural features obtained from F-18 FDG PET/CT offer clinical value that can predict the outcome of patients with locally advanced cervical cancer (LACC) receiving concurrent chemoradiotherapy (CCRT). METHODS: We reviewed the records of 68 patients with stage IIB-IVA LACC who underwent PET/CT before CCRT. Conventional metabolic parameters, shape indices, and textural features of the primary tumor were measured on PET/CT. A Cox regression model was used to examine the effects of variables on overall survival (OS) and progression-free survival (PFS). RESULTS: The patients included in this study were classified into two groups based on median value of PET/CT parameters. The high group of GLNU derived from GLRLM is only independent prognostic factor for PFS (HR 7.142; 95% CI 1.656-30.802; p = 0.008) and OS (HR 9,780; 95% CI 1.222-78.286; p = 0.031). In addition, GLNU derived from GLRLM (AUC 0.846, 95% CI 0.738-0.923) was the best predictor for recurrence among clinical prognostic factors and PET/CT parameters. CONCLUSION: Our results demonstrated that high GLNU from GLRLM on pretreatment F-18 FDG PET/CT images, were significant prognostic factors for recurrence and death in patients with LACC receiving CCRT.

Temporal changes of periodontal tissue pathology in a periodontitis animal model.

PURPOSE: This study aimed to characterize the early stages of periodontal disease and determine the optimal period for its evaluation in a mouse model. The association between the duration of ligation and its effect on the dentogingival area in mice was evaluated using micro-computed tomography (CT) and histological analysis. METHODS: Ninety mice were allocated to an untreated control group or a ligation group in which periodontitis was induced by a 6-0 silk ligation around the left second maxillary molar. Mice were sacrificed at 1, 2, 3, 4, 5, 8, 11, and 14 days after ligature placement. Alveolar bone destruction was evaluated using micro-CT. Histological analysis was performed to assess the immune-inflammatory processes in the periodontal tissue. RESULTS: No significant difference in alveolar bone loss was found compared to the control group until day 3 after ligature placement, and a gradual increase in alveolar bone loss was observed from 4 to 8 days following ligature placement. No significant between-group differences were observed after 8 days. The histological analysis demonstrated that the inflammatory response was evident from day 4. CONCLUSIONS: Our findings in a mouse model provide experimental evidence that ligature-induced periodontitis models offer a consistent progression of disease with marginal attachment down-growth, inflammatory infiltration, and alveolar bone loss.

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.