Exploring the effect of BRCA1/2 status on chemotherapy-induced hematologic toxicity in patients with ovarian cancer.

OBJECTIVE: BRCA1/2 are integral to the DNA repair mechanism and their germline pathogenic variants (gBRCA) result in a high risk for developing breast and ovarian cancer. Patients with gBRCA mutations showed increased sensitivity to DNA cross-linking agent but might have increased treatment-related toxicities. Thus, we hypothesized that gBRCA mutation ovarian cancer patients who underwent platinum-based chemotherapy might be at higher risk of developing chemotherapy-induced hematologic toxicity. METHODS: This study enrolled 160 patients with ovarian cancer who received frontline platinum-based chemotherapy between 2011 and 2019 in Kyungpook National University Chilgok Hospital. Incidence rate and severity of chemotherapy-induced hematologic toxicity (neutropenia, anemia, thrombocytopenia) was compared for BRCA mutation and wild patients. RESULTS: 160 women, including 62 BRCA1/2 (38 BRCA1, and 25 BRCA2) mutation group, and 98 noncarriers, were analyzed. A higher frequency of G2 anemia was noted in the BRCA -mutant group (22% vs. 1%, p = 0.07). Furthermore, G3 anemia was significantly common among BRCA group (12.9% vs. 3%, p = 0.02). In the subgroup analysis according to BRCA1/2 status, BRCA1 mutated patients showed a significantly higher frequency of G1 anemia than BRCA2 (89% vs. 60%, p = 0.01). In terms of neutropenia and thrombocytopenia, BRCA mutated patients and noncarriers had similar hematologic toxicity. CONCLUSION: Germline BRCA mutations were associated with a higher frequency of G2/3 anemia in ovarian cancer patients who underwent first-line platinum-based chemotherapy. Moreover, the BRCA1 mutation appeared to be more strongly associated with the incidence of chemotherapy-induced anemia. Our findings warrant further investigation in larger, prospective studies to confirm these current findings and determine whether preventive interventions may be necessary.

Comparison of serum anti-Müllerian hormone between unilateral and bilateral ovarian endometriomas during follicular, luteal, and random menstrual phases: a retrospective study.

BACKGROUND: Over the last two decades, serum levels of anti-Müllerian hormone (AMH) have been shown to be reliable markers of ovarian reserve. This study aimed to compare baseline serum AMH levels and well-controlled clinical factors between patients with unilateral and bilateral ovarian endometriomas during the menstrual phase. METHODS: We conducted a retrospective study. We enrolled 136 patients aged 18 to 36 years who were diagnosed with unilateral or bilateral ovarian endometriomas. Serum AMH levels of all patients and their latest two to three menstrual cycles were measured before surgery for ovarian endometriomas. The latest menstrual cycle length ranged from 26 to 30 days. Patients with irregular menstruation, a recent medication history of hormonal drugs other than oral contraceptive pills, a previous history of ovarian surgery, or any medical history influencing ovarian function were excluded. RESULTS: Of the 136 patients, 76 (55.9%) had unilateral ovarian endometriomas and 60 (44.1%) had bilateral ovarian endometriomas. Serum AMH levels were not significantly different between the two groups in the follicular phase, luteal phase, or at any random time point. CONCLUSION: Serum AMH levels were not significantly different between unilateral and bilateral ovarian endometriomas in the follicular and luteal phases, or at any random time during the menstrual cycle when various confounding factors were excluded.

Transcriptomic Network Analysis Using Exfoliative Cervical Cells Could Discriminate a Potential Risk of Progression to Cancer in HPV-related Cervical Lesions: A Pilot Study.

BACKGROUND/AIM: Cervical cancer is the fourth most common type of cancer in women worldwide and it is a major cause of cancer-related deaths in developing countries. Despite the marked reduction observed in the rates of the disease as a result of screening programs, it is necessary to develop robust biomarkers that can detect the neoplastic progression early in HPV-related cervical lesions. MATERIALS AND METHODS: We performed comparative mRNA sequencing from exfoliative cervical cytology samples from nine Korean women using the Illumina NovaSeq6000 platform. Each pathological tissue was matched to the corresponding cytological sample. The pathologic diagnosis was scrutinized with ancillary immunohistochemistry and was considered a confirmative (endpoint) diagnosis. The pathological diagnoses consisted of three cases of chronic cervicitis, 2 high-grade squamous intraepithelial lesions (HSILs), 2 squamous cell carcinomas in situ (CIS), and 2 invasive squamous cell carcinomas (SQCCs), respectively. Using bioinformatic analyses, differentially expressed genes (DEGs; fold change ≥1.5; p<0.05) were applied for Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and protein-protein interaction (PPI) networks. RESULTS: From a total of 55,882 genes, 438 DEGs were pinpointed; 282 genes were up-regulated and 156 genes down-regulated. These transcriptomic profiles were clearly divided into neoplastic (HSIL, CIS, and SQCC; ≥HSILs) and non-neoplastic lesions. The up-regulated DEGs were HIF-1a, EDN1, PIK3R3, PPP1CA and AKR1C1. GO, GSEA, and PPI network analyses showed marked associations with metabolism, proteolysis, or proteoglycan process pathways in cervical carcinogenesis. CONCLUSION: The transcriptomic analysis using exfoliative cervical cells was more likely representative of its corresponding histopathological diagnosis, thus emphasizing its potential utility in clinical practice. This study provides comprehensive transcriptomic network analyses for robust biomarkers that might present a high potential risk of progression to cancer in the exfoliative cervical cytology; our findings support their clinical utility for improved cervical cancer screening.

Comparison of Multi- and Single-Site Robotic Myomectomy Using the Da Vinci® SP Surgical System: A Propensity Score Matching Analysis.

Objective: This study aimed to compare the surgical outcomes between robotic multi-site myomectomy (RMSM) and robotic single-site myomectomy (RSSM), using the da Vinci® SP surgical system and perform propensity score matching analysis to ensure inter-group comparability. Methods: This retrospective study included 105 patients who underwent either three-incision RMSM or RSSM using the da Vinci® SP surgical system. We retrospectively reviewed and compared surgical outcomes using 1:1 propensity score matching. Results: After 1:1 propensity score matching, there were no differences in the total operation time and estimated blood loss between the groups. The docking time (p < 0.0001) and duration of hospital stay (p = 0.0001) were significantly shorter in the RSSM group than in the RMSM group. Conclusions: The surgical outcomes of RSSM were comparable to those of RMSM. Moreover, compared to RMSM, RSSM using the da Vinci® SP surgical system has shorter docking and morcellation times, and duration of hospital stay.

Is ovarian cystectomy for atypical ovarian endometrioma safe?: A single center study.

Ovarian atypical endometriosis (AE) is a premalignant lesion, and its potential to progress to endometriosis-associated ovarian cancer emphasizes its significance. However, the true risk of malignancy in AE remains unclear. Therefore, this study aimed to investigate the clinical outcomes of ovarian AE after ovarian cystectomy. We retrospectively reviewed the medical records and histopathological reports of 41 patients who had been diagnosed with ovarian AE between January 2011 and April 2020. We reviewed age, obstetric history, age at menarche, preoperative CA 125 level, C-reactive protein level, erythrocyte sedimentation rate, endometriosis stage, mean follow-up duration, postoperative hormonal therapy, and prognosis, including recurrence of endometriosis and malignant transformation. Among 41 patients with pathologically diagnosed ovarian AE, 26 were followed up after cystectomy only. The average follow-up period was 58.27 ± 33.22 months in cystectomy only patients. The mean age of the patients with cystectomy only versus that of patients with endometriosis-associated ovarian carcinoma was 32.73 ± 6.10 versus 48.29 ± 4.35 (P < .01) years. The preoperative CA 125 level was 115.63 ± 219.06 versus 225.75 ± 163.39 (P < .051) U/mL. Patients with endometriosis-associated ovarian carcinoma or other diseases and those who underwent oophorectomy were excluded. After surgery, hormone therapy was administered to 22 of 26 patients, and the remaining 4 patients were followed up without additional treatment. Endometriosis recurrence occurred in 5 patients, 1 of whom underwent second-line laparoscopic ovarian cystectomy. However, no malignant transformations were observed. Ovarian AE has a low possibility of malignant transformation. Conservative treatment is recommended after appropriate ovarian cystectomy, such as enucleation.

Survival Outcomes With Reduced Doses of Adjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer.

BACKGROUND/AIM: There have not been enough recent studies investigating the incidence or efficacy of dose reduction in adjuvant chemotherapy for epithelial ovarian cancer. This study examined whether patients who needed dose reduction showed poorer survival outcomes. PATIENTS AND METHODS: From 2011 to 2021, 102 patients were included in the study. Patients who underwent neoadjuvant chemotherapy and those with early-stage disease were excluded. Patients were divided into two groups: those who had a ≥60% dose reduction during the whole period of first-line adjuvant chemotherapy, and those with dose reductions <60%. Of the 102 patients, 38 (37.3%) underwent dose reduction ≥60%. RESULTS: PFS was significantly longer in the group whose dose reductions were ≥60%, whereas OS was not significant. CONCLUSION: A dose reduction of ≥60%, determined by patients' medical conditions, during first-line of adjuvant chemotherapy does not negatively influence survival outcomes, such as OS and PFS, in advanced epithelial ovarian cancer.

Comparison of Survival Outcomes According to BRCA1/2 Variant Type in High-grade Serous Ovarian Cancer.

BACKGROUND/AIM: Mutations of BRCA1/2 improve cancer prognosis due to their better response to platinum-based chemotherapy. This study evaluated overall survival (OS) and progression-free survival (PFS) under similar conditions of first-line adjuvant chemotherapy within seven years in high-grade serous ovarian cancer (HGSOC). PATIENTS AND METHODS: A total of 160 patients were enrolled. The pathogenic BRCA1/2 variant group included pathogenic variant and likely-pathogenic variant, while the non-pathogenic group included wild-type and variant of uncertain significance. For first-line chemotherapy, delivered dose intensity, relative dose intensity, and delay of duration were calculated in all patients. RESULTS: Of the tested variants, 108 (67.5%) were non-pathogenic and 52 (32.5%) were pathogenic. No significant difference was found in various clinical factors of cancer stage, surgery, or chemotherapy. There was no significance for OS or PFS within five or seven years. CONCLUSION: In patients with HGSOC, the OS and PFS for germline BRCA1/2 pathogenic and non-pathogenic variants were not significantly different under similar conditions of first-line adjuvant chemotherapy within seven years.

Survival Impact of Residual Cancer Cells in Intraoperative Peritoneal Washes following Radical Hysterectomy for Cervical Cancer.

OBJECTIVE: Residual cancer cells (RCCs) contribute to cancer recurrence either because of tumor spillage or undetectable pre-existing micrometastatic tumor clones. We hypothesized that the pathologic evaluation of intraoperative peritoneal washes may reveal RCCs. The aim of this study was to evaluate the survival impact of RCCs identified in intraoperative peritoneal washes and their correlation with clinicopathologic parameters following radical hysterectomy for cervical cancer. METHODS: A total of 229 patients with cervical cancer who underwent radical hysterectomy with pelvic and/or paraaortic lymphadenectomy were included. The intraoperative peritoneal washes after surgery were filtered through a strainer and the presence of tumor cells in the residual aspirate was determined. Univariate and multivariate analyses of clinicopathological parameters were performed to identify predictors of recurrence. RESULTS: RCCs in intraoperative peritoneal washes were identified in 19 patients (8.3%). Multivariate analysis revealed that deep stromal invasion (hazard ratio [HR], 13.32; 95% confidence interval [CI], 1.81-98.27; p = 0.0111), lymph node metastasis (HR, 2.00; 95% CI, 1.01-3.99; p = 0.0482), and neoadjuvant chemotherapy (HR, 2.34; 95% CI, 1.89-4.61; p = 0.0139) were associated with tumor recurrence. However, the presence of RCCs was not associated with tumor recurrence (HR, 2.60; 95% CI, 0.74-9.11; p = 0.1352). Multiple logistic regression analysis revealed that RCCs were associated with neoadjuvant chemotherapy (odds ratio [OR], 0.22; 95% CI, 0.05-0.99; p = 0.0488) and large tumor size (OR, 4.16; 95% CI, 0.77-22.48; p = 0.0981). CONCLUSIONS: Although the presence of RCCs in intraoperative peritoneal washes do not significantly impact survival outcomes, there was a tendency of inferior survival outcomes in patients with RCCs. RCCs were associated with neoadjuvant chemotherapy and large tumor size.

Correlation Between Clinical Outcomes and Serum CA-125 Levels After Standard Treatment for Epithelial Ovarian Cancer.

BACKGROUND/AIM: To analyze the relationship between clinical outcomes for epithelial ovarian cancer and serum CA-125 levels after chemotherapy in Korean women. PATIENTS AND METHODS: This study included 183 patients who underwent the standard treatment regimen for epithelial ovarian cancer. They were divided into early- (I, II) and advanced-stage (III, IV) groups. Serum CA-125 level after adjuvant chemotherapy completion (post-chemotherapy; PC-CA-125) was measured. Overall survival (OS), progression-free survival (PFS), platinum-free interval (PFI), and platinum resistance were evaluated. RESULTS: In advanced-stage group, OS, PFS, PFI, and platinum resistance were significantly correlated with PC-CA-125. In early-stage group, PFS and platinum resistance differed significantly. Cutoff value for platinum resistance was 10.45 U/ml, 10.40 U/ml, and 15.80 U/ml for study population, early stage, and advanced groups, respectively. Accuracy was 71.1%-77.1%. CONCLUSION: PC-CA-125 is correlated with clinical outcomes in ovarian cancer. Thus, CA-125 can be used to predict platinum resistance in ovarian cancer treatment.

Applicability of the Histoculture Drug Response Assay to Predict Platinum Sensitivity and Prognosis in Ovarian Cancer.

BACKGROUND/AIM: To retrospectively analyze the results of histoculture drug response assays (HDRAs) to determine whether the results could predict platinum sensitivity and prognosis in ovarian cancer. PATIENTS AND METHODS: One hundred thirty-nine patients with ovarian cancer were reviewed. HDRAs were conducted for platinum and taxane agents. Platinum resistance and sensitivity occurred in 21 and 118 patients, respectively. To analyze the relationship between the inhibition rates (IRs) of tumor growth caused by the platinum agent and clinical outcomes, Student's t-test and linear regression analysis were used. RESULTS: We found that the average IRs of the platinum and taxane agent were not statistically significant between the platinum-sensitive and - resistant groups. There was no statistical significance for overall survival, progression-free survival, or platinum-free interval. CONCLUSION: The HDRA is not useful for predicting platinum sensitivity and survival outcomes.

Prognostic Value of Lymph Node Characteristics in Patients with Cervical Cancer Treated with Radical Hysterectomy.

OBJECTIVE: This study evaluated the prognostic value of various lymph node (LN) characteristics, including the lymph node ratio (LNR), in patients with cervical cancer treated with radical hysterectomy. METHODS: In this retrospective study, 260 patients with cervical cancer who had undergone radical hysterectomy with pelvic or paraaortic lymphadenectomies were included. LN characteristics related to several LN statuses included total LN counts, LN metastasis, total positive LN counts, LNR, and levels of lymphadenectomy. LNR was defined as the number of metastatic LNs divided by the total number of LNs harvested. Univariate and multivariate analyses for disease-free survival (DFS) and overall survival (OS) were performed using the clinicopathological and LN characteristics. RESULTS: Based on receiver-operating characteristics curve analysis, the cut-off value of LNR was 0.0625. Multivariate analysis revealed that high LNR was significantly related to tumor recurrence (hazard ratio [HR], 5.182; 95% confidence interval [CI], 2.424-11.075; p < 0.0001). After adjusting for clinicopathological factors, LNR was also independent prognostic factor for predicting tumor recurrence (HR, 5.930; 95% CI, 2.114-16.634; p = 0.0007). However, total retrieved LN counts and level of lymphadenectomy were not associated with survival outcomes. CONCLUSION: LNR may be a prognostic biomarker for predicting disease recurrence in cervical cancer treated with radical hysterectomy.

Association between gestational age at delivery and lymphocyte-monocyte ratio in the routine second trimester complete blood cell count.

BACKGROUND: We aimed to determine whether routine second trimester complete blood cell (CBC) count parameters, including neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-lymphocyte ratio (PLR), could predict obstetric outcomes. METHODS: We included singleton pregnancies for which the 50-g oral glucose tolerance test and CBC were routinely performed between 24 and 28 weeks of gestation in our outpatient clinic from January 2015 to December 2017. The subjects were divided into three groups according to their pregnancy outcomes as follows: group 1, spontaneous preterm births, including preterm labor and preterm premature rupture of membranes; group 2, indicated preterm birth due to maternal, fetal, or placental causes (hypertensive disorder, fetal growth restriction, or placental abruption); and group 3, term deliveries, regardless of the indication of delivery. We compared the CBC parameters using a bivariate correlation test. RESULTS: The study included 356 pregnancies. Twenty-eight subjects were in group 1, 20 in group 2, and 308 in group 3. There were no significant differences between the three groups in neutrophil, monocyte, lymphocyte, and platelet counts. Although there was no significant difference in NLR, LMR, and PLR between the three groups, LMR showed a negative correlation with gestational age at delivery (r=-0.126, p=0.016). CONCLUSION: We found that a higher LMR in the second trimester was associated with decreased gestational age at delivery. CBC parameters in the second trimester of pregnancy could be used to predict adverse obstetric outcomes.

Prognostic Value of Hematological Parameters in Locally Advanced Cervical Cancer Patients Treated With Concurrent Chemoradiotherapy.

BACKGROUND/AIM: We evaluated the clinical implications of pre- and post-treatment hematological parameters as prognostic factors in patients with locally advanced cervical cancer (LACC) who received definitive concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: We retrospectively analyzed 125 patients with LACC (FIGO stage IIB to IIIB) who received definitive CCRT. Clinical factors and hematological parameters, including neutrophil-to-lymphocyte ratio (NLR) were assessed pre- and post-CCRT. Univariate and multivariate analysis for disease-free survival (DFS) and overall survival (OS) were performed using clinicopathological and hematological parameters. RESULTS: Disease recurred in 46 (36.8%) patients, and 24 patients (19.2%) died. On multivariate analysis, post-treatment NLR, ΔNLR (pre-treatment NLR/post-treatment NLR) and ΔPLR (platelet-to-lymphocyte ratio) (pretreatment PLR/post-treatment PLR) were significant prognostic factors for DFS, and only post-treatment NLR was a significant prognostic factor for OS (p<0.001). However, pre-treatment hematological parameters were not associated with prognosis. CONCLUSION: Post-treatment hematological parameters, particularly NLR, may serve as a prognostic indicator in patients with LACC who received definitive CCRT.

Androgen receptor cytosine, adenine, and guanine trinucleotide repeat polymorphism in Korean patients with endometriosis: A case-control study.

STUDY OBJECTIVE: To investigate the association between the androgen receptor (AR) cytosine, adenine, and guanine (CAG) repeat polymorphisms and endometriosis. STUDY DESIGN: A prospective case-control, genetic association study was performed on women with surgically proven endometriosis (n=421) and controls free of endometriosis (n=349). AR CAG repeat lengths were determined from peripheral blood samples. The difference in the frequency of each alleles were compared in patients with endometriosis and controls using Chi-square test. MAIN RESULTS: No significant difference in biallelic length mean between patients and controls was observed. Alleles containing 24 CAG repeats were significantly more frequent in stage I-II (mild) endometriosis than in the control samples (19.8% and 13.3%, respectively; OR 1.60, 95% CI 1.04-2.47). Additionally, a higher frequency of both alleles with 24 or more CAG repeats was observed in individuals with mild endometriosis, in comparison with the controls (25.6% and 15.2%, respectively; OR 1.92, 95% CI 1.09-3.38). CONCLUSIONS: AR gene CAG repeat polymorphisms are associated with the increased risk of mild endometriosis.

Gene dose effect between a fat mass and obesity-associated polymorphism and body mass index was observed in Korean women with polycystic ovary syndrome but not in control women.

OBJECTIVE: To examine the association between fat mass and obesity-associated (FTO) polymorphisms and polycystic ovary syndrome (PCOS) in Korean women. DESIGN: Case-control study. SETTING: University department of obstetrics and gynecology. PATIENT(S): Women with (n = 552) or without (n = 559) PCOS. INTERVENTION(S): Genotyping was performed. MAIN OUTCOME MEASURE(S): FTO rs9939609 genotype distribution and correlation between variants in this gene and PCOS phenotypes. RESULT(S): The mean body mass index (BMI) of the patients was significantly higher than that of the control subjects (22.0 ± 4.1 kg/m(2) vs. 20.1 ± 2.5 kg/m(2)), but most (81.3%) of the patients were not obese. FTO rs9939609 was not significantly associated with PCOS itself. However, a positive correlation was observed between the number of variant alleles and BMI in women with PCOS: Each additional copy of the variant allele increased BMI by a mean (95% confidence interval) of 4.8% (1.4%-8.3%) or 1.11 kg/m(2) (1.03-1.20 kg/m(2)) after adjusting for age. This correlation was not observed in the control subjects. CONCLUSION(S): FTO rs9939609 was not a major determinant of PCOS. However, in the women with PCOS who were primarily nonobese, a gene dose effect was observed for BMI. The FTO gene may play an influential role in predisposition to PCOS via an association with obesity.

In vitro inhibitory effect of flavonoids on growth, infection and vacuolation of Helicobacter pylori.

Flavonoids, which are main constituents of herbal medicines, have been reported to inhibit the growth of Helicobacter pylori (HP). Therefore, to evaluate the anti-HP activity of some flavonoids (flavanols, flavones, flavonols and isoflavonoids), their effects on the growth and vacuolation of HP as well as the infective properties of HP against HeLa cells were investigated. Catechins, quercetin and naringenin weakly inhibited the growth of HP, but all tested compounds did not inhibit HP infection into KATO III cells and HP urease activity. Quercetin and naringenin inhibited HP VacA vacuolation in HeLa cells with IC (50) values of 0.046 and 0.36 mM, respectively. Quercetin also inhibited procaspase-3 activation to caspase-3 in HeLa cells induced by HP VacA toxin, which may induce cell death via the proteolytic activation of a cascade of caspases. However, quercetin did not affect Bax and Bcl-2 protein levels. Based on these findings, quercetin may improve gastric cell death by inhibiting apoptotic signaling by HP VacA toxin. Abbreviations. HP: Helicobacter pyloriBSA:bovine serum albumin ESL:enhanced chemiluminescence MIC:minimum inhibitory concentration MTT:methylthiazolyldiphenyl-tetrazolium bromide PBS:phosphate-buffered saline VacA:Vacuolating cytotoxin.