Prognostic impact of erythropoietin-stimulating agent use during front-line chemotherapy in patients with ovarian cancer: A Korean multicenter cohort study.

OBJECTIVE: To evaluate whether treatment with erythropoiesis-stimulating agents (ESAs) for chemotherapy-induced anemia affects progression-free survival (PFS) in patients receiving front-line chemotherapy following surgery for ovarian cancer (OC). METHODS: We retrospectively reviewed all consecutive patients who received front-line chemotherapy after surgery between 2013 and 2019 at six institutions. The patients were divided according to the use of ESAs during front-line chemotherapy. The primary endpoint was PFS. The secondary endpoint was the occurrence of thromboembolism. Propensity score matching (PSM) analysis was used to compare survival between matched cohorts. RESULTS: Overall, 2147 patients (433 receiving ESA and 1714 for no-ESA) were identified, with a median follow-up of 44.0 months. The ESA group showed a significantly higher proportion of stage III/IV disease (81.8% vs 61.1%; P < 0.001) and postoperative gross residual disease (32.3% vs 21.2%; P < 0.001) than the no-ESA group. In the multivariable Cox regression analysis, the use of ESAs did not affect PFS (adjusted hazard ratio, 1.03; 95% confidence interval [CI]: 0.89-1.20; P = 0.661). The incidence of thromboembolism was 10.2% in the ESA group and 4.6% in the no-ESA group (adjusted odds ratio, 6.58; 95% CI: 3.26-13.28; P < 0.001). When comparing the well-matched cohorts after PSM, PFS did not differ between the ESA (median PFS 23.5 months) and no-ESA groups (median PFS 22.2 months) (P = 0.540, log-rank test). CONCLUSIONS: The use of ESAs during front-line chemotherapy did not negatively affect PFS in patients with OC after surgery but increased the risk of thromboembolism.

MGMT Methylation Is Associated with Human Papillomavirus Infection in Cervical Dysplasia: A Longitudinal Study.

Cervical premalignancy/malignancy, as detected by cervical cytology or biopsy, can develop as a result of human papillomavirus (HPV) infection. Meanwhile, DNA methylation is known to be associated with carcinogenesis. In this study, we thus attempted to identify the association between MGMT methylation and persistent HPV infection using an Epi-TOP MPP assay. Integrative analysis of DNA methylation was carried out here using longitudinal cervical cytology samples of seven patients with atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (ASC-US/LSIL). Then, a gene expression analysis using the longitudinal cervical cytology samples and a public database (The Cancer Genome Atlas (TCGA)) was performed. Upon comparing the ASC-US or LSIL samples at the 1st collection and the paired samples at the 2nd collection more than 6 months later, we found that they became hypermethylated over time. Then, using the longitudinal data, we found that the MGMT methylation was associated with HPV infection. Moreover, TCGA dataset revealed an association between downregulated MGMT mRNA expression and poor overall survival. This decreased MGMT mRNA expression was observed to have an inverse relationship with MGMT methylation levels. In this study, we found that the MGMT methylation level could potentially serve as a valuable prognostic indicator for the transition from ASC-US/LSIL to cervical cancer.

Menstrual and Reproductive Factors for Gastric Cancer in Postmenopausal Women: The 2007-2020 Korea National Health and Nutrition Examination Survey.

Globally, the incidence of gastric cancer is lower in women than in men. It is thought that menstrual and reproductive factors may be related to their lower incidence of gastric cancer. This cross-sectional study examined menstrual, reproductive, and other factors in 20,784 postmenopausal women from the 2007-2020 Korea National Health and Nutrition Examination Survey (KNHANES). A univariate logistic regression analysis was performed, and then a multivariate logistic regression analysis for significant factors in the univariate analysis was conducted. In the multivariate logistic regression analysis, the age at menarche (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.00-1.06, p = 0.035) and myocardial infarction (OR 2.43, 95% CI 1.05-5.62, p = 0.026) showed a significant association with increased incidence of gastric cancer. The age at menopause (OR 0.97, 95% CI 0.95-1.00, p = 0.03), the age at the first childbirth (OR 0.93, CI 0.89-0.97, p = 0.007), and the experience of alcohol consumption (OR 0.68, 95% CI 0.5-0.91, p = 0.003) showed a significant association with a decreased incidence of gastric cancer. Late menarche, early menopause, early aged first childbirth, and myocardial infarction are estimated to be risk factors for gastric cancer in postmenopausal Korean women.

Recurrent atypical leiomyoma in bladder trigone, confused with uterine fibroids: A case report.

BACKGROUND: Tumors originating from the posterior bladder wall can be challenging to diagnose because they may mimic a mass from the uterine cervix. Atypical leiomyoma of the bladder trigone is extremely rare, with few reported cases, and requires caution during surgery to avoid damage to the adjacent ureter. Diagnostic surgery and confirmational pathology are essential to assess whether the tumor is malignant and relieve clinical symptoms. Herein, we describe a case of recurrent leiomyoma with focal atypia in the bladder trigone. CASE SUMMARY: A 29-year-old woman with a uterine fibroid incidentally found at a regular checkup was referred to our hospital. Based on magnetic resonance imaging, either urinary bladder leiomyoma or protrusion of pedunculated uterine cervical fibroid into the bladder was suspected. This leiomyoma in the trigone of the bladder was completely excised by laparotomy, and the patient was discharged without complication. Follow-up outpatient ultrasonography identified tumor recurrence after four years. As focal atypia was identified previously, laparotomy was performed to confirm the pathology. A round solid mass was resected from the posterior bladder wall without injuring either ureteric orifice. This tumor was pathologically diagnosed as a leiomyoma without atypia. Three-year follow-up ultrasonography has revealed no recurrence. CONCLUSION: Atypical leiomyoma in bladder trigone is rare and could be easily mistaken for fibroid in the uterine cervix. To confirm histopathology, surgical excision is mandatory and regular follow-up is necessary to detect recurrence.

Intra and extra pelvic multidisciplinary surgical approach of retroperitoneal sarcoma: Case series report.

BACKGROUND: Retroperitoneal sarcoma (RPS) is a rare malignancy arising from mesenchymal cells that most commonly presents as an abdominal mass and is associated with poor prognosis. Although several studies have assessed the survival benefits of wide excision, few have reported detailed methods for achieving wide excision in patients with RPS. AIM: To describe our experience with multidisciplinary surgical resection of RPS using intra- and extra-pelvic approaches. METHODS: Multidisciplinary surgery is an anatomical approach that combines intra- and extra-peritoneal access within the same surgery to achieve complete RPS removal. This retrospective review of the records of patients who underwent multidisciplinary surgery for RPS analyzed surgical and survival outcomes. RESULTS: Eight patients underwent 10 intra- and extra-pelvic surgical resections, and their median mass size was 12.75 cm (range, 6-45.5 cm). Using an intrapelvic approach, laparoscopy-assisted surgery was performed in four cases and laparotomy surgery in six. Using an extrapelvic approach, ilioinguinal and posterior approaches were used in four cases each, and the prone position and midline skin incision were shared in one. All patients' RPS masses were removed completely, and four achieved R0 resection through intra- and extra-pelvic surgery. The median estimated blood loss was 2000 mL (range, 300-20000 mL) and the median hospitalization was 12.6 d (range, 9-69 d). Reoperation was needed in two patients (one for wound necrosis and the other for bowel perforation and wound necrosis). The median overall survival rate and median progression-free survival were 64.6 and 13.7 mo, respectively. CONCLUSION: RPS is therapeutically challenging because of its location and high risk of recurrence. Therefore, intra- and extra-pelvic surgical approaches can improve the macroscopic security of the surgical margin.

A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer.

BACKGROUND: PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer. METHODS: Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101. DISCUSSION: PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04678102 .

Preoperative neutrophil-to-lymphocyte, platelet-to-lymphocyte and monocyte-to-lymphocyte ratio as a prognostic factor in non-endometrioid endometrial cancer.

Objective: Evaluate the prognostic value of neutrophil-lymphocyte ratio (NMR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) in patients with non-endometrioid endometrial cancer. Method: Laboratory and clinicopathological data from 118 patients with non-endometrioid endometrial cancer who underwent surgical resection between January 2010 and December 2019 were reviewed. NLR, PLR and MLR were analyzed for correlations with recurrence and survival. The receiver operating characteristic (ROC) curves were generated for the NLR, PLR, and MLR. Optimal cut-off values were determined as the points at which the Youden index (sensitivity + specificity - 1) was maximal. Based on the results of the ROC curve analysis, the patients were grouped into high MLR and low MLR groups. Recurrence rate, disease-free survival, and overall survival were compared between the two groups. The prognostic factors were investigated using univariate and multivariate Cox proportional hazards model. Results: The optimal cut-off value of MLR was 0.191 (AUC, 0.718; p < 0.001). Significantly more patients in the high MLR group experienced recurrence (60.3% vs. 15.6%, p < 0.0001) and cancer-related deaths (46.6% vs. 13.3%, p = 0.003). In multivariate analysis, advanced stage and high MLR were independent prognostic factors for disease-free survival and overall survival. Conclusion: Elevated MLR was significantly associated poor clinical outcomes in patients with non endometrioid endometrial cancer. Our findings suggest that MLR may be clinically reliable and useful as an independent prognostic marker for patients with non-endometrioid endometrial cancer.

An Application of Machine Learning That Uses the Magnetic Resonance Imaging Metric, Mean Apparent Diffusion Coefficient, to Differentiate between the Histological Types of Ovarian Cancer.

This retrospective single-center study included patients diagnosed with epithelial ovarian cancer (EOC) using preoperative pelvic magnetic resonance imaging (MRI). The apparent diffusion coefficient (ADC) of the axial MRI maps that included the largest solid portion of the ovarian mass was analysed. The mean ADC values (ADCmean) were derived from the regions of interest (ROIs) of each largest solid portion. Logistic regression and three types of machine learning (ML) applications were used to analyse the ADCs and clinical factors. Of the 200 patients, 103 had high-grade serous ovarian cancer (HGSOC), and 97 had non-HGSOC (endometrioid carcinoma, clear cell carcinoma, mucinous carcinoma, and low-grade serous ovarian cancer). The median ADCmean of patients with HGSOC was significantly lower than that of patients without HGSOCs. Low ADCmean and CA 19-9 levels were independent predictors for HGSOC over non-HGSOC. Compared to stage I disease, stage III disease was associated with HGSOC. Gradient boosting machine and extreme gradient boosting machine showed the highest accuracy in distinguishing between the histological findings of HGSOC versus non-HGSOC and between the five histological types of EOC. In conclusion, ADCmean, disease stage at diagnosis, and CA 19-9 level were significant factors for differentiating between EOC histological types.

Abdominal wall mass suspected of endometriosis: clinical and pathologic features.

OBJECTIVE: To evaluate the clinical and pathological characteristics of lower anterior abdominal wall masses suspicious for endometriosis. METHODS: A retrospective review of 38 patients who underwent surgery for a lower anterior abdominal wall mass suspicious for endometriosis was performed. Those with skin and intraperitoneal masses, lipomas, hernias, and metastatic malignant masses were excluded. Patient age, body mass index, delivery history, dysmenorrhea, and mass size and location were analyzed. RESULTS: Thirty-seven (97.3%) patients had a relevant surgical history, including 35 (92.1%) with a history of cesarean section (C/S). Among the three patients with no history of C/S, 1 underwent total abdominal and another total laparoscopic hysterectomy, and 1 had no previous surgical history. The mean (±standard deviation) size of the abdominal masses was 3.2±1.2 cm. One patient developed a recurrent mass after excision of abdominal wall endometriosis. Trocar site endometrioma was found in one patient following total laparoscopic hysterectomy. According to the final pathology reports, endometriosis was found in 35 (92.1%) of patients. The remaining 3 patients (7.9%) had malignancy: adenocarcinoma, squamous cell carcinoma, and extra-gastrointestinal stromal tumor. Before surgery, only 3 patients (7.9%) underwent fine-needle aspiration biopsy of the masses, which were all postoperatively confirmed to be pathologically benign. CONCLUSION: Although most abdominal wall masses in the present sample were endometriosis occurring at the scar site from a previous operation, 7.9% of patients ultimately exhibited malignancy. Therefore, all patients with suspected anterior wall endometriosis should undergo preoperative biopsy to identify the few that will have an alternative diagnosis.