Body composition and peri- and postoperative complications in patients with gynaecological malignancies: A systematic review.

BACKGROUND: In general abdominal surgery, the ratio of fat to muscle mass, or body composition measures, shows a stronger association with complications than body mass index. These studies include male and female patients. Women have a different body composition than men. Therefore, findings from general abdominal surgery cannot be extrapolated to women with cancer. The aim of this systematic review is to summarise the evidence on the association between body composition and peri- and postoperative complications in patients with gynaecological cancer. METHODS: Pubmed, Embase and the Cochrane Central databases were searched in June 2023. Studies were eligible if they included patients undergoing surgery for gynaecological cancer and reported on the association between body composition (muscle or fat mass) and surgical complications. The quality of the studies was assessed using the Newcastle-Ottawa quality assessment scale. A best-evidence synthesis was used to summarise the level of evidence. RESULTS: Fifteen studies were included that assessed muscle mass (n = 9) or fat mass (n = 6). We found strong evidence that there was no association between visceral fat and length of hospital stay. We found moderate evidence that a higher amount of good quality muscle was associated with a lower risk of postoperative complications. We found moderate evidence that there was no association between muscle or fat mass (i.e., muscle- or subcutaneous fat) and postoperative complications or fat mass and intraoperative complications. There was insufficient evidence for an association between visceral fat and intraoperative or postoperative complications, and for an association between muscle mass or -quality and length of hospital stay. There was high heterogeneity in the methods used to measure body composition, hampering meta-analyses. CONCLUSION: The association between body composition, particularly adipose tissue and muscle quality, and complications suggests that these measures may be of interest in determining postoperative risk in women undergoing surgery for gynaecological cancer.

Impact of risk-reducing salpingo-oophorectomy on lipid determinants, HbA1c and CRP.

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) is advised before 40-45 years of age for BRCA1/2 mutation carriers. This study describes the effect of RRSO on lipid determinants, hemoglobin A1c (HbA1c) and C-reactive protein (CRP). METHODS: A total of 142 women with increased risk of ovarian cancer were included, 92 premenopausal and 50 postmenopausal. Serum levels of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and total cholesterol, triglycerides, HbA1c and CRP were determined at three points in time: before (T0) and 6 weeks (T1) and 7 months (T2) following RRSO. The Hot Flush Rating Scale was administered at the same time points. RESULTS: In premenopausal women, levels of HDL-cholesterol, the cholesterol ratio and HBA1c increased significantly over time, although still staying within the reference range. In this group, hot flushes increased over time (p < 0.001). In postmenopausal women, no significant changes were observed following RRSO. At T2, serum LDL-cholesterol, triglycerides, HbA1c and CRP were significantly lower in premenopausal women compared to postmenopausal women, whereas HDL was increased. CONCLUSIONS: Seven months after RRSO, the lipid profile in premenopausal women had changed, although still staying within the reference range. For postmenopausal women, we did not observe any significant changes. Our results do not suggest a worsening of cardiovascular risk within 7 months of RRSO.

Experiences, adherence and satisfaction with a combined exercise and dietary intervention for patients with ovarian cancer undergoing chemotherapy: A mixed-methods study.

OBJECTIVE: This study examined experiences, adherence and satisfaction with a combined exercise and dietary intervention in patients with ovarian cancer and their healthcare professionals (HCPs) as part of the randomized PADOVA trial. METHODS: A mixed-methods approach was used in 24 patients with ovarian cancer receiving first-line chemotherapy who were randomly allocated to a combined exercise and dietary intervention or usual care with counseling sessions post-treatment. Qualitative data on intervention experiences, adherence and satisfaction was collected using semi-structured interviews with patients and their HCPs (n = 18 physical therapists; n = 5 dietitians). Quantitative data on adherence and satisfaction was collected to provide context to qualitative data. RESULTS: Exercise relative dose intensity ranged from 36 to 100% (median 72%) and patients attended 33-133% (median 100%) of the prescribed dietary counseling sessions. Patients appreciated guidance on exercise and nutrition and perceived benefits including improved physical fitness, quality of life, peer support and recovery after surgery and/or chemotherapy cycles. Both patients and HCPs were satisfied with the intervention and perceived that participation exceeded prior expectations. Median patient satisfaction score with the intervention was 8.5 out of 10. Suggestions for improving the intervention included further personalization of the number, content and scheduling of the sessions to preferences of patients and HCPs. Patients in the usual care group reported counseling sessions post-chemotherapy to be too little too late. CONCLUSIONS: Patients with ovarian cancer adhered well to the intervention. Numerous perceived benefits of the intervention were reported by patients and HCPs. Good adherence and positive experiences support successful implementation in clinical practice.

The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: a review.

This paper briefly reviews the role of hypermethylation of host cell genes in cervical carcinogenesis and discusses potential clinical applications of methylation analysis in the management of high-risk HPV (hrHPV) -positive women. We argue that methylation assays can be used: 1. for primary triage of hrHPV-positive women to detect cervical cancer and advanced cervical intraepithelial neoplasia (CIN); 2. as secondary triage for women with minor cytological abnormalities to identify those with the highest risk of CIN3 or worse; 3. as exit test for women leaving the screening programme to identify cervical cancer and advanced CIN; and 4. to support management of CIN. TWEETABLE ABSTRACT: This paper discusses potential clinical applications of DNA methylation analysis in the management of women with a high-risk HPV infection.

The effect of adjuvant chemotherapy on survival in patients with FIGO stage I high-grade serous ovarian cancer.

OBJECTIVE: The benefit of adjuvant chemotherapy for FIGO stage I, high-grade serous ovarian cancer (HGSOC) after optimal staging is a matter of debate. We investigated the effect of adjuvant chemotherapy on recurrence-free survival (RFS) and overall survival (OS) in a population-based cohort study. METHODS: All patients diagnosed in the Netherlands between 2002 and 2014 with FIGO stage I HGSOC who underwent surgical staging were included. Data on clinical characteristics, histopathology, completeness of staging and survival were collected from the Netherlands Cancer Registry and Dutch Pathology Registry. Recurrence data was collected from hospital files. We used Kaplan-Meier methods to estimate RFS and OS and Cox-proportional hazard analyses to control for differences in baseline characteristics between patients who did or did not receive chemotherapy. RESULTS: We identified 223 patients who underwent optimal staging procedures including lymph node sampling. Events of disease recurrence occurred in 21 of the 101 patients (21%) who received adjuvant chemotherapy and in 46 of the 122 patients (38%) who did not (multivariable hazard ratio (HR), 0.37; 95%CI 0.22-0.64; p < 0.01). Five-year RFS was 81% after staging plus chemotherapy and 59% after staging only. At a median follow-up of 105 months, 21 patients (21%) in the chemotherapy group and 38 patients (31%) in the no-chemotherapy group had died (multivariable HR 0.50; 95%CI 0.28-0.89; p = 0.02). Ten-year OS was 78% with chemotherapy and 62% without chemotherapy. CONCLUSIONS: Adjuvant chemotherapy improves long-term RFS and OS in patients with FIGO stage I HGSOC after optimal staging.

HPV-based cervical screening: Rationale, expectations and future perspectives of the new Dutch screening programme.

Based on scientific data showing that HPV testing provides better protection against cervical precancer and cancer than cytology, in 2011 the Dutch Health Council advised the Minister of Welfare, Health and Sports to replace cytology by HPV testing in the Dutch population-based screening programme. After a successful evaluation of the feasibility of HPV-based screening in 2014, primary HPV testing for cervical screening was implemented in 2017. The Netherlands has been one of the first countries worldwide to implement nationwide HPV-based screening and its experience with the new programme is therefore followed with great interest. In this manuscript, we present an overview of the studies that were instrumental in the choice of HPV assay and triage strategy, the adjustment of screening starting and exit ages and intervals, and the implementation of HPV self-sampling. Finally, we review the cost-effectiveness of the proposed new screening algorithm and we explore future perspectives. The rationale behind the new Dutch HPV-based screening programme, which is based on risk management, could serve as a guidance to other countries that are planning to implement HPV-based screening in the near future.

Safety of hormone replacement therapy following risk-reducing salpingo-oophorectomy: systematic review of literature and guidelines.

Background: Women at high risk to develop ovarian cancer opt for risk-reducing salpingo-oophorectomy (RRSO) to reduce the risk by 80-96%. RRSO leads to a direct onset of menopause in premenopausal women. Hormone replacement therapy (HRT) can be used to mitigate menopausal symptoms after RRSO. However, it is unclear whether HRT in these women is safe in terms of breast cancer (BC) risk. Methods: We performed a literature search and investigated national guidelines on the use of HRT following RRSO in BRCA1 and BRCA2 mutation carriers. We analyzed differences and similarities between the guidelines and describe what these guidelines were based upon. Results: Seven articles regarding HRT following RRSO in BRCA1 and BRCA2 mutation carriers were identified. None of the included studies yielded any evidence that short-term use of HRT following RRSO increases the risk of developing BC or negates the protective effect of RRSO in BRCA1/2 mutation carriers without a personal history of BC. Eleven national guidelines were found and described. Conclusion: Short-term use of HRT after RRSO seems to be safe. The literature is more favorable toward estrogen alone. The ideal dosage and duration of use are unknown and remain to be investigated in future studies.

'DURVIT': a phase-I trial of single low-dose durvalumab (Medi4736) IntraTumourally injected in cervical cancer: safety, toxicity and effect on the primary tumour- and lymph node microenvironment.

BACKGROUND: Treatment with programmed cell death receptor (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors is a promising strategy to lift tumour-induced immune response suppression. However, the current systemic treatment often causes autoimmune side effects. In more than 50% of squamous cell cervical cancer, PD-L1 expression is detected. Moreover, we observed high and interrelated rates of PD-L1 positive macrophages and regulatory T cells in metastatic lymph nodes of cervical cancer patients. As cervical cancer in general initially metastasizes to regional lymph nodes, local administration of durvalumab (a PD-L1 checkpoint inhibitor) at an early stage will deliver these antibodies exactly where they are needed, facilitating immune protection. This may result in a clinical benefit while reducing undesirable side effects. METHODS: DURVIT is a non-randomized, single-arm, open-label, phase I study. Three escalating dose levels of intratumourally (i.t.) injected durvalumab will be tested, i.e. 5, 10 and 20 mg (three patients per dose level, with an additional three at the highest tolerated dose). The primary endpoint of this phase-I study is safety. Immune monitoring will consist of flow cytometric, immunohistochemical and functional T cell reactivity testing. The first patient has been included in this trial in November 2017. DISCUSSION: Evidence of safety and biological efficacy of this locally administered checkpoint blockade may expand adjuvant therapy options for cervical cancer patients. Early metastatic spread of cervical cancer cells may thus be controlled in the draining lymph node basin, and beyond, and hopefully delay or even prevent the onset of disease recurrence. TRIAL REGISTRATION: NTR6119 , 1-nov-2016.

Does anti-Müllerian hormone predict change in menopausal symptoms following risk-reducing salpingo-oophorectomy? A prospective observational study.

OBJECTIVES: The aim of this study was to investigate whether serum anti-Müllerian hormone (AMH) predicts symptom burden after risk-reducing salpingo-oophorectomy (RRSO) in order to individualize counseling. METHODS: Patient-reported menopausal symptoms, sexual functioning, and psychological distress (depression and anxiety) were assessed 1 day before (T0) and 6 weeks (T1) and 7 months (T2) after RRSO. AMH was assessed before RRSO. Multivariable regression analysis was used to investigate the association between AMH and short-term and long-term change in symptom burden following RRSO. RESULTS: Ninety-one premenopausal women at high risk of ovarian cancer were included. Presurgical AMH was not related significantly to change in symptoms post RRSO. As a secondary outcome we found that regular menses before RRSO was associated specifically with long-term increase in hot flushes (sr = 0.40, p = 0.001; total R2 = 0.171) and depression (sr = 0.29, p = 0.012; total R2 = 0.132). Earlier receipt of chemotherapy was associated with long-term improvement in sexual functioning (sr = 0.24, p = 0.041; total R2 = 0.348). CONCLUSION: In this cohort, AMH was not a significant predictor of change in symptoms following RRSO. Regular menses prior to RRSO and earlier receipt of chemotherapy were significantly, but relatively weakly, associated with changes in outcomes 6 weeks and/or 7 months after RRSO.

Sexual distress and associated factors among cervical cancer survivors: A cross-sectional multicenter observational study.

BACKGROUND: To assess whether sexual distress among cervical cancer (CC) survivors is associated with frequently reported vaginal sexual symptoms, other proposed biopsychosocial factors and whether worries about painful intercourse mediate the relation between vaginal sexual symptoms and sexual distress. METHODS: A cross-sectional study was conducted among 194 sexually active partnered CC survivors aged 25 to 69 years. Sexual distress, vaginal sexual symptoms, sexual pain worry, anxiety, depression, body image concerns, and relationship dissatisfaction and the sociodemographic variables age, time since treatment, and relationship duration were assessed by using validated self-administrated questionnaires. RESULTS: In total, 33% (n = 64) of the survivors scored above the cut-off score for sexual distress. Higher levels of sexual distress were shown to be associated with higher levels of vaginal sexual symptoms, sexual pain worry, relationship dissatisfaction, and body image concerns. Furthermore, the results showed that sexual pain worry partly mediated the association between vaginal sexual symptoms and sexual distress, when controlling for relationship dissatisfaction and body image concerns. CONCLUSIONS: Appropriate rehabilitation programs should be developed for CC survivors to prevent and reduce not only vaginal sexual symptoms but also sexual pain worry, relationship dissatisfaction, and body image concerns to reduce sexual distress.