G-CSF Induces Neutrophil Extracellular Traps Formation and Promotes Ovarian Cancer Peritoneal Dissemination.

Epithelial ovarian cancer is characterized by aggressive peritoneal dissemination. Neutrophils are mobilized to peritoneal cavity in some patients with ovarian cancer dissemination, however, its pathological significance remains unknown. This study aimed to investigate the role of neutrophil extracellular traps (NETs) in ovarian cancer dissemination. We conducted a retrospective analysis of clinical data and samples from 340 patients with ovarian cancer who underwent primary surgery between 2007 and 2016 at the Osaka University Hospital. In vitro, NETs formation was induced by stimulating human peripheral neutrophils. The human ovarian cancer cell line, OVCAR8, was co-cultured with NETs. For an ovarian cancer dissemination mouse model, we performed an intraperitoneal injection of OVCAR8 cells into nude mice. The association between NETs and peritoneal dissemination was explored, and model mice were treated with the peptidylarginine deiminase 4 (PAD4) inhibitor GSK484 to assess antitumor efficacy. Neutrophilia (neutrophil count >7000/mm3) correlated with shorter survival, advanced peritoneal dissemination, elevated granulocyte colony-stimulating factor (G-CSF) levels, increased neutrophil count in ascites, and augmented NETs foci in peritoneal dissemination sites. In vitro assays revealed that G-CSF stimulated neutrophils to form NETs, promoting cancer cell adhesion. In vivo investigations revealed that G-CSF-producing tumor-bearing mice had accelerated peritoneal dissemination and poor prognosis. NETs formation was pathologically observed at the peritoneal dissemination sites. Inhibition of NETs formation by GSK484 significantly delayed peritoneal dissemination in vivo. In conclusion, G-CSF was associated with intra-abdominal NETs formation and increased peritoneal dissemination. NETs represent potential therapeutic targets for ovarian cancer, particularly in patients with neutrophilia.

Obstetrical outcomes of labor with and without analgesia in Robson classification groups 1 and 2a: a single-center retrospective study.

PURPOSE: This study aimed to elucidate the effects of neuraxial analgesia on labor in women classified based on the Robson classification system. METHODS: We retrospectively reviewed the clinical data of singleton cephalic nulliparous deliveries in labor at term between January 2018 and December 2021 and compared obstetrical outcomes between deliveries with and without neuraxial analgesia in women of Robson group 1 (spontaneous labor) and group 2a (induced labor). Statistical analyses were performed using the Wilcoxon ranked-sum test, Fisher's exact test, and logistic regression model. Statistical significance was set at p < 0.05. RESULTS: We identified 2726 deliveries during the period, of which 387 deliveries (215 with analgesia and 172 without analgesia) were in Robson group 1 and 502 deliveries (258 with analgesia and 244 without analgesia) in Robson 2a. In Robson group 1 pregnancies, the cesarean section (CS) rate was higher in those who received analgesia (15%) than in those who did not (3%) (p = 0.0001). Multivariate analysis revealed that labor with analgesia was a significant risk factor for CS (p < 0.0001). Similarly, in Robson group 2a pregnancies, we observed a higher CS rate in those with analgesia than in those without analgesia (18 vs. 11%, p = 0.042). CONCLUSION: A higher CS rate was observed in deliveries with analgesia than in those without analgesia both in the Robson group 1 and group 2a pregnancies.

Magnetic resonance imaging evaluation of pelvic floor structure during pregnancy.

OBJECTIVE: Among the various risk factors of pelvic floor disorders, pregnancy has been reported to affect the pelvic floor structure; however, not all these effects have been understood yet. The aim of this study is to elucidate how pregnancy affects pelvic floor structure via magnetic resonance imaging (MRI). STUDY DESIGN: We conducted a retrospective study between January 2010 and December 2019 to extract clinical records of pregnant and non-pregnant women, who underwent MRI for obstetrical diseases and ovarian benign tumors, respectively. The data on age, body mass index (BMI), complications, gravida, parity, gestational age, and obstetrical history were collected, and pubo-coccygeal line (PCL), pubo-rectal line (PRL), and M line (ML) on their MR images were measured. Statistical analyses were performed with Wilcoxon test, chi-square test, and Kruskal-Wallis test with Steel-Dwass post hoc test as appropriate. Statistical significance was set at P < 0.05. RESULTS: We analyzed the reports of 56 (pregnancy group) and 106 women (non-pregnancy group). There was no significant difference in age or BMI, while the obstetric history was significantly different between these groups. Median PCL, PRL, and ML in the pregnancy group were significantly longer than those in the non-pregnancy group (114.1 mm vs. 110.0 mm, P = 0.018; 48.6 mm vs. 41.6 mm, P < 0.0001 and 21.7 mm vs. 10.0 mm, p < 0.0001. respectively). The subgroup analysis of the effect of pregnancy and vaginal delivery (VD) history on changes in these lines revealed that pregnancy-induced PRL increase tended to recover to the reference level of "non-pregnant without VD," but ML increase did not fully recover. CONCLUSION: MRI revealed a strong effect of pregnancy on pelvic floor structure.