New immune phenotypes for treatment response in high-grade serous ovarian carcinoma patients.

Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision. Patients' immune status broadly reflects the tumor cell biological behavior and the patient responses to disease and treatment. Serum cytokine profiling is a sensitive measure of immune adaption and deviation, yet its integration into treatment paradigms is underexplored. This study is part of the IMPACT trial (NCT03378297) and aimed to characterize immune responses before and during primary treatment for HGSOC to identify biomarkers for treatment selection and prognosis. Longitudinal serum samples from 22 patients were collected from diagnosis until response evaluation. Patients underwent primary cytoreductive surgery or neoadjuvant chemotherapy (NACT) based on laparoscopy scoring. Twenty-seven serum cytokines analyzed by Bio-Plex 200, revealed two immune phenotypes at diagnosis: Immune High with marked higher serum cytokine levels than Immune Low. The immune phenotypes reflected the laparoscopy scoring and allocation to surgical treatment. The five Immune High patients undergoing primary cytoreductive surgery exhibited immune mobilization and extended progression-free survival, compared to the Immune Low patients undergoing the same treatment. Both laparoscopy and cytoreductive surgery induced substantial and transient changes in serum cytokines, with upregulation of the inflammatory cytokine IL-6 and downregulation of the multifunctional cytokines IP-10, Eotaxin, IL-4, and IL-7. Over the study period, cytokine levels uniformly decreased in all patients, leading to the elimination of the initial immune phenotypes regardless of treatment choice. This study reveals distinct pre-treatment immune phenotypes in HGSOC patients that might be informative for treatment stratification and prognosis. This potential novel biomarker holds promise as a foundation for improved assessment of treatment responses in patients with HGSOC. ClinicalTrials.gov Identifier: NCT03378297.

Primary Treatment Effects for High-Grade Serous Ovarian Carcinoma Evaluated by Changes in Serum Metabolites and Lipoproteins.

High-grade serous ovarian carcinoma (HGSOC) is the most common and deadliest ovarian cancer subtype. Despite advances in treatment, the overall prognosis remains poor. Regardless of efforts to develop biomarkers to predict surgical outcome and recurrence risk and resistance, reproducible indicators are scarce. Exploring the complex tumor heterogeneity, serum profiling of metabolites and lipoprotein subfractions that reflect both systemic and local biological processes were utilized. Furthermore, the overall impact on the patient from the tumor and the treatment was investigated. The aim was to characterize the systemic metabolic effects of primary treatment in patients with advanced HGSOC. In total 28 metabolites and 112 lipoproteins were analyzed by nuclear magnetic resonance (NMR) spectroscopy in longitudinal serum samples (n = 112) from patients with advanced HGSOC (n = 24) from the IMPACT trial with linear mixed effect models and repeated measures ANOVA simultaneous component analysis. The serum profiling revealed treatment-induced changes in both lipoprotein subfractions and circulating metabolites. The development of a more atherogenic lipid profile throughout the treatment, which was more evident in patients with short time to recurrence, indicates an enhanced systemic inflammation and increased risk of cardiovascular disease after treatment. The findings suggest that treatment-induced changes in the metabolome reflect mechanisms behind the diversity in disease-related outcomes.

A multicenter interventional program to reduce the incidence of anal sphincter tears.

OBJECTIVE: In Norway, we have experienced a gradual increase in the incidence of obstetric anal sphincter injuries from under 1% in the late 1960s to 4.3% in 2004. This study was aimed to assess whether an interventional program causes a decrease in the frequency of anal sphincter tears. METHODS: In all, 40,152 vaginal deliveries between 2003 and 2009 were enrolled in the interventional cohort study from four Norwegian obstetric departments. The focus of the intervention was on manual assistance during the final part of the second stage of labor. Data were analyzed in relation to occurrence of obstetric anal sphincter tears. RESULTS: The proportion of parturients with anal sphincter tears decreased from 4-5% to 1-2% during the study period in all four hospitals (P<.001). The tears associated with both noninstrumental and instrumental deliveries decreased dramatically. The number of patients with grades 3 and 4 anal sphincter ruptures decreased significantly, and the reduction was most pronounced in grade 4 tears (-63.5%) and least in 3c tears (-47.5%) (both P<.001). The number of episiotomies increased in two hospitals but remained unchanged in the other two. The lowest proportion of tears at the end of the intervention (1.2% and 1.3%, respectively) was found in the two hospitals with an unchanged episiotomy rate. CONCLUSION: The multicenter intervention caused a highly significant decrease in obstetric anal sphincter injuries. LEVEL OF EVIDENCE: II.