Laparoscopic Surgery for Ovarian Neoplasms - What is Possible, What is Useful?

The use of minimally invasive surgical techniques is becoming increasingly important in gynecologic oncology due to technical advances and the increasing level of surgical expertise. In addition to laparoscopic approaches for the treatment of benign neoplasms, minimally invasive surgical methods have also become established in some areas for treating gynecologic malignancies. For tumor entities such as endometrial and cervical carcinoma, there are conclusive studies emphasizing the role of laparoscopy in surgical therapy. By contrast, due to a lack of prospective data with survival analyses, no clear conclusions can be drawn on the significance of laparoscopy in the surgical treatment of ovarian carcinoma. However, some smaller, mostly retrospective case-control studies and cohort studies open the way for a discussion, positing the possibility that laparoscopic surgical procedures, particularly for early ovarian carcinoma, are technically feasible and of a quality equivalent to that of conventional longitudinal laparotomy, and may also be associated with lower perioperative morbidity. In this article we discuss the most important aspects of using minimally invasive surgical techniques for ovarian carcinoma based on the current literature. In particular we look at the relevance of laparoscopy as a primary approach for surgical staging of early ovarian carcinoma, and we evaluate the role of diagnostic laparoscopy in assessing the operability of advanced ovarian carcinoma.

Influence of anesthetic technique on survival after tumor debulking surgery of elderly patients with ovarian cancer: Results of a retrospective cohort study.

Epidural analgesia could influence the postoperative oncologic outcomes in patients with specific types of non-metastatic solid neoplasms. The present study aimed to investigate the impact of anesthetic technique on survival in elderly patients with ovarian cancer (OC). The records of all women with OC older than 60 years of age undergoing tumor debulking surgery at the University Medical Center of the Johannes Gutenberg University Mainz (Mainz, Germany) between January 2008 and December 2019 were obtained. The study cohort was divided into two groups based on the use of perioperative epidural anesthesia or not. First, Kaplan-Meier analysis was performed to analyze the prognostic influence of anesthetic technique on survival. Second, multivariate Cox proportional hazards model was adjusted for multiple conventional prognostic factors concerning three main categories: i) Current clinical-pathological tumor characteristics; ii) anesthesiologic parameters, including mean age, American Society of Anesthesiologists Performance Status and preexisting comorbidities summarized in the Charlson Comorbidity Index; and iii) oncological and surgical parameters such as oncological radicality and Surgical complexity Score. A total of 110 patients were included in the study and 71 (64.5%) of them received epidural analgesia. The median survival time was 26.0 months from primary debulking surgery and no significant differences in progression-free (PFS) and overall survival (OS) were noted between the 'Epidural' and 'non-Epidural' cohorts. After adjustment for the selected risk factors from the three categories, the effects of epidural analgesia on PFS and OS remained non-significant [PFS: hazard ratio (HR), 1.26; 95% CI, 0.66-2.39; and OS: HR, 0.79; 95% CI, 0.45-1.40]. The present results did not support the independent association between epidural-supplemented anesthesia and improved PFS or OS in elderly patients with standardized ovarian cancer debulking surgery.

Prognostic Impact of LAG-3 mRNA Expression in Early Breast Cancer.

Background: Monoclonal antibodies against PD-1 or PD-L1 have been established in clinical practice for the treatment of both early and advanced/metastatic triple-negative breast cancer. Beyond the established immune checkpoints (ICPs) (PD-1 and CTLA-4), additional ICPs, such as lymphocyte activation gene-3 (LAG-3), are subject of current research. In the present retrospective gene-expression analysis, we evaluated the prognostic significance of LAG-3 in 461 patients with early breast cancer. In addition, we examined whether there was a correlation between the different ICP and CD8 expressions. Methods: Using microarray-based gene-expression analysis, we examined the prognostic significance of LAG-3 mRNA expression for metastasis-free survival (MFS) in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed using Spearman's rho correlation coefficient. Results: In the whole cohort, LAG-3 expression had no significant impact on MFS (p = 0.712, log-rank). In the subgroup analyses, there was a trend that a higher LAG-3 expression was associated with a favorable outcome in the luminal B (p = 0.217), basal-like (p = 0.370) and HER2 (p = 0.089) subtypes, although significance was not reached. In contrast, in a multivariate Cox regression analysis, adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and proliferation marker Ki-67, LAG-3 showed a significant influence on MFS (HR 0.574; 95% CI 0.369−0.894; p = 0.014). High LAG-3 significantly correlated with CD8 (ρ = 0.571; p < 0.001). Conclusions: LAG-3 expression had an independent impact on MFS. In addition to PD-1 and PD-L1, further immune checkpoints, such as LAG-3, could serve as therapeutic targets in breast cancer.

Resilience as a Source of Easement to Health-Related Worries in Women at Increased Risk for Breast or Ovarian Cancer During the COVID-19 Pandemic.

Purpose: The COVID-19 pandemic has affected individuals' and society's physical and psychological well-being. The study was conducted in order to assess the predictors for health-related worries during the COVID-19 pandemic in vulnerable populations. Patients and Methods: A cross-sectional web-based survey of women who had a higher risk of developing breast cancer (BC) or ovarian cancer (OC) was conducted, regardless of whether they had experienced an active malignant disease during the pandemic. A self-reported questionnaire was designed for this study to assess health-related worries. The PHQ-4 questionnaire was used to evaluate mental health, and the Brief Resilience Scale (BRS) questionnaire was employed to investigate resilience. Results: History of BC or OC was recognized as an independent significant risk factor for worries regarding being more susceptible to a more severe course of COVID-19 disease (OR 3.593; 95% CI 1.030-12.536; p = 0.045). High scores in the BRS questionnaire were negatively correlated with health-related worries, such as an increased risk for occurrence of BC or OC (OR 0.332; 95% CI 0.118-0.933; p = 0.37) or worsening of oncological outcome as a result of an infection with the SARS-CoV-2 virus (OR 0.330; 95% I 0.114-0.956; p = 0.041). Conclusion: The obtained findings determined resilience as an independent and potent protective parameter in terms of health-related concerns in women at high risk for BC and OC. The results may assist in identifying women at risk for health-related concerns during adverse life events, allowing healthcare providers to respond fast and according to the patients´ needs.

Patients' expectations of preventive measures of medical institutions during the SARS-CoV-2 pandemic in Germany in women with an increased risk of breast and ovarian cancer: a cross-sectional, web-based survey.

OBJECTIVES: To identify patient-approved contingency measures for protection of patients and healthcare workers (HCWs) from COVID-19 infection and to use these findings to improve staff's preparedness to cope with the course of this pandemic or similar situations. METHODS DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS: We conducted a cross-sectional, web-based survey of women with an increased risk of breast or ovarian cancer, regardless of whether they had experienced an active malignant disease during the pandemic. A self-reported questionnaire, developed for this study, was used to assess expectations and opinions about preventive measures within medical institutions. RESULTS: Sixty-four (71.9%) of the 89 potential participants responded to at least one question regarding contingency measures within medical institutions. Approximately 37% of the respondents preferred having information about their facility's hygiene protocols before appointment; 57.8% of the respondents endorsed regular SARS-CoV-2 testing of patients prior to medical appointments and 95.3% endorsed regular testing of HCWs. Additionally, 84.4% of the respondents supported HCWs' use of surgical masks and 68.8% supported HCWs' use of masks with greater protection. Notably, 75.0% of the respondents advocated for the presence of a significant other during medical consultations; 71.9% approved the use of telemedicine and 93.8% endorsed changes in appointment practices to enable social distancing. No significant associations were found between respondents' sociodemographic, disease-specific or pandemic-specific factors and their opinions on hygiene precautions. CONCLUSIONS: Patients at high risk of infection or severe course of COVID-19 approve strict contingency measures designed to lower the transmission of COVID-19 in medical facilities. Moreover, vulnerable groups may profit from contingency plans in healthcare facilities in order to follow preventive measures, avoid diagnostic delay or avoid worsening of pre-existing conditions. However, they also value the presence of a significant other during medical consultations and procedures.

Zinc accelerates respiratory burst termination in human PMN.

The respiratory burst of phagocytes is essential for human survival. Innate immune defence against pathogens relies strongly on reactive oxygen species (ROS) production by the NADPH oxidase (NOX2). ROS kill pathogens while the translocation of electrons across the plasma membrane via NOX2 depolarizes the cell. Simultaneously, protons are released into the cytosol. Here, we compare freshly isolated human polymorphonuclear leukocytes (PMN) to the granulocytes-like cell line PLB 985. We are recording ROS production while inhibiting the charge compensating and pH regulating voltage-gated proton channel (HV1). The data suggests that human PMN and the PLB 985 generate ROS via a general mechanism, consistent of NOX2 and HV1. Additionally, we advanced a mathematical model based on the biophysical properties of NOX2 and HV1. Our results strongly suggest the essential interconnection of HV1 and NOX2 during the respiratory burst of phagocytes. Zinc chelation during the time course of the experiments postulates that zinc leads to an irreversible termination of the respiratory burst over time. Flow cytometry shows cell death triggered by high zinc concentrations and PMA. Our data might help to elucidate the complex interaction of proteins during the respiratory burst and contribute to decipher its termination.