The influence of the menstrual cycle and hormonal contraceptives on cardiorespiratory fitness in physically active women: A systematic review and meta-analysis.

OBJECTIVE To systematically review and summarize the existing evidence related to the influence of the menstrual cycle (MC) and hormonal contraceptive (HC) use on O2max in physically active women. METHODS This systematic review and meta-analysis conforms to the PRISMA statement guidelines. Four (sub-)meta-analyses were performed. Two focused on longitudinal studies examining the same women several times to compare the O2max during the different menstrual phases or oral contraceptive (OC) use and withdrawal. Two meta-analyses examined if there is a difference in O2max between OC users and normally menstruating women by analyzing cross-sectional studies assigning physically active women to one of these two groups as well as intervention-based studies (cross-over studies, randomized controlled trials considering only the data of the intervention group) comparing women intra-individually with and without OCs. RESULTS Nine of the included studies (107 women) evaluated the influence of the MC, five studies (69 women) the impact of OCs on O2max, and six studies investigated both topics (88 women). A mean difference of O2max -0.03 ml/kg/min (95%CI -1.06 to 1.01) between the early follicular and luteal menstrual phase was observed. Between the active and inactive phases of OCs, a mean difference of -0.11 ml/kg/min (95%CI -2.32 to 2.10) was found. The inter-individual comparison of naturally menstruating women and OC users showed a mean difference in O2max of 0.23 ml/kg/min (95% CI -2.33 to 2.79) in favor of OC use. The intra-individual comparison of the same women showed a mean decrease in O2max of -0.84 ml/kg/min (95% CI -2.38 to 0.70) after a new start with OCs. CONCLUSIONS Our meta-analyses showed no effects of the MC or the OCs on O2max. More high-quality studies are needed determining the MC phases more precisely, including OCs with the current standard formulations and comparing the influence of different progestins

Preoperative smoking cessation program in patients undergoing intermediate to high-risk surgery: a randomized, single-blinded, controlled, superiority trial

BACKGROUND At present, effectively implementing smoking cessation programs in the health care system constitutes a major challenge. A unique opportunity to initiate smoking cessation focuses on smokers scheduled for surgery. These patients are not only highly motivated to quit smoking but also likely to benefit from a reduction in postoperative complications which may translate into a decrease of costs. Nevertheless, surgical patients are not routinely informed about the benefits of preoperative smoking cessation. Potential reasons for this missed opportunity may be the lack of time and training of surgeons and anaesthesiologists. We therefore aim to analyse the impact of a preoperative high-intensity smoking cessation intervention on surgical complications up to a 90-day postoperative period in patients of various surgical disciplines. The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing intermediate to high-risk surgery. METHODS The present study is a single-centre, randomized trial with two parallel groups of smokers scheduled for surgery comparing surgery alone and surgery with preoperative smoking cessation. We plan to randomize 251 patients. The primary objective is to compare complications between patients with an institutional multifaceted smoking cessation intervention starting 4 weeks before surgery compared to patients in the advice-only group (control group) within a 90-day postoperative period. The primary endpoint is the Comprehensive Complication Index (CCI®) within 90 days of surgery. Secondary outcomes include the length of hospital stay, cost of care, quality of life, smoking abstinence, and reduction in nicotine consumption. DISCUSSION The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing surgery. TRIAL REGISTRATION BASEC #2021-02004; ClinicalTrials.gov: NCT05192837 . Registered on January 14, 2022

The immunologic tumor microenvironment in endometrioid endometrial cancer in the morphomolecular context: mutual correlations and prognostic impact depending on molecular alterations

OBJECTIVE POLE-mutant, microsatellite-instable (MSI), p53-mutant and non-specific molecular profile (NSMP) are TCGA-defined molecular subgroups of endometrial cancer (EC). Hypothesizing that morphology and tumor immunology might differ depending on molecular background concerning composition and prognostic impact, we aimed to comprehensively interconnect morphologic, immunologic and molecular data. METHODS TCGA-defined molecular groups were determined by immunohistochemistry and sequencing in n = 142 endometrioid EC. WHO-defined histopathological grading was performed. The immunologic microenvironment (iTME) was characterised by the quantification of intraepithelial and stromal populations of tumor-infiltrating lymphocytes (TIL: overall T-cells; T-Killer cells; regulatory T-cells (Treg)). Immunologic parameters were correlated with WHO-grading, TCGA-subgroups and prognosis. RESULTS High density TIL were significantly more frequent in high-grade (G3) compared to low-grade (G1/2) EC in the whole cohort and in the subgroup of POLE-wildtype-/microsatellite-stable-EC. MSI was associated with high-level TIL-infiltration when taking into account the type of mismatch repair defect (MLH1/PMS2; MSH2/MSH6). Prognostic impact of biomarkers depended on molecular subgroups: In p53-mutant EC, Treg were independently prognostic, in NSMP, the unique independently prognostic biomarker was WHO-grading. CONCLUSIONS EC morphology and immunology differ depending on genetics. Our study delineated two molecularly distinct subgroups of immunogenic EC characterized by high-density TIL-infiltration: MSI EC and high-grade POLE-wildtype/microsatellite-stable-EC. Prognostic impact of TIL-populations relied on TCGA-subgroups indicating specific roles for TIL depending on molecular background. In NSMP, histopathological grading was the only prognostic biomarker demonstrating the relevance of WHO-grading in an era of molecular subtyping

Recent Advances in Cervical Cancer Treatment

Cervical cancer refers to the malignant transformation of cervical epithelial or glandular cells, primarily attributed to persistent infection with high-risk human papillomavirus (HPV) genotypes. Recurrent or metastatic cervical cancer is characterized by an unfavorable prognosis and a high mortality rate. Although incorporating the anti-angiogenic agent bevacizumab into treatment protocols has led to enhanced survival rates, a significant number of patients with disease progression following initial platinum-based chemotherapy have limited therapeutic options. This paper aims to provide an overview of the current progress in cervical cancer treatment strategies, with a focus on the most relevant, potentially practice-changing results of recent phase III clinical trials

Lifestyle modifications after the diagnosis of gynecological cancer

Background!#!The influence of lifestyle factors on the quality of life, incidence and tumor recurrence has been evaluated in several studies and is gaining increasing importance in cancer research. However, the extent of the influence of such lifestyle factors on the quality of life of cancer patients remains largely unclear, as does the number of patients actually pursuing these lifestyle changes. The purpose of this study was to examine the prevalence and predictors of lifestyle changes in patients with gynecological cancer.!##!Methods!#!The survey consisted of a pseudonymous questionnaire that was conducted from January to May 2014 via a telephone interview with 141 patients with a gynaecological malignancy who had undergone surgery at our Department of Gynaecology and Obstetrics. Lifestyle factors (diet, physical activity, stress level, alcohol and nicotine consumption) prior to and after the diagnosis of cancer were evaluated.!##!Results!#!89% (n = 125) of the patients reported lifestyle changes after being diagnosed with cancer. There was a significant association between the implementation of lifestyle changes and age as well as the use of complementary medicine. Nutrition: 66% of the patients (n = 93) consumed more fruit and vegetables and 65% ate less meat (n = 92). Physical activity: 37% (n = 52) reported no change in their exercise routine, 36% (n = 51) described a decrease, 27% (n = 38) an increase in their physical activity. Subjective feeling of stress: 77% of the patients (n = 108) described a reduction in their perceived level of stress. Nicotine consumption: 63% (n = 12) of the 19 patients who were smokers at the time of the diagnosis quit or reduced smoking thereafter. Alcohol consumption: 47% (n = 61/129) of the patients reduced their alcohol consumption.!##!Conclusions!#!Most of the patients from our study group implemented lifestyle changes after being diagnosed with cancer. Prospective randomized trials are needed in order to determine the benefit of lifestyle changes (physical activity, dietary habits and stress reduction) for cancer survivors. The potential impact of lifestyle on the quality of life and the trajectory of the disease should be discussed with all oncological patients

Interpatient Heterogeneity in Drug Response and Protein Biomarker Expression of Recurrent Ovarian Cancer

Recurrent ovarian-cancer patients face low 5-year survival rates despite chemotherapy. A variety of guideline-recommended second-line therapies are available, but they frequently result in trial-and-error treatment. Alterations and adjustments are common in the treatment of recurrent ovarian cancer. The drug response of 30 lesions obtained from 22 relapsed ovarian cancer patients to different chemotherapeutic and molecular agents was analyzed with the patient-derived ovarian-cancer spheroid model. The profile of druggable biomarkers was immunohistochemically assessed. The second-line combination therapy of carboplatin with gemcitabine was significantly superior to the combination of carboplatin with PEGylated liposomal doxorubicin (p < 0.0001) or paclitaxel (p = 0.0007). Except for treosulfan, all nonplatinum treatments tested showed a lesser effect on tumor spheroids compared to that of platinum-based therapies. Treosulfan showed the highest efficacy of all nonplatinum agents, with significant advantage over vinorelbine (p < 0.0001) and topotecan (p < 0.0001), the next best agents. The comparative testing of a variety of treatment options in the ovarian-cancer spheroid model resulted in the identification of more effective regimens for 30% of patients compared to guideline-recommended therapies. Recurrent cancers obtained from different patients revealed profound interpatient heterogeneity in the expression pattern of druggable protein biomarkers. In contrast, different lesions obtained from the same patient revealed a similar drug response and biomarker expression profile. Biological heterogeneity observed in recurrent ovarian cancers might explain the strong differences in the clinical drug response of these patients. Preclinical drug testing and biomarker profiling in the ovarian-cancer spheroid model might help in optimizing treatment management for individual patients

Epithelial–mesenchymal transition (EMT) in vulvar cancer with and without inguinal lymph node involvement

Purpose!#!Epithelial-mesenchymal transition (EMT) is associated with increased metastatic spread and poor prognosis. Data on vulvar carcinoma are limited.!##!Methods!#!Thirty-two cases of squamous cell carcinoma of the vulva (16 with and 16 without inguinal lymph node metastases) and their lymph node deposits were evaluated for immunohistochemical expression of EMT markers (vimentin, cyclin D1, e-cadherin), p16, p53 and Ki-67. Results of EMT-immunostainings were compared to lymph node involvement and expression of p53 and p16. The micro-anatomical staining pattern for EMT markers comparing the tumor center with the front of invasion was analysed in each tumor.!##!Results!#!There was no difference in the expression of EMT markers between node negative and node positive tumors. Staining for vimentin and cyclin D1 was seen within tumor cells at the front of invasion in 100 and 84.4% of the tumors, respectively. The majority of cases (68.7%) showed negative or reduced staining for e-cadherin in this micro-anatomical localization. Tumor cells within the lymph node metastases showed positive staining for e-cadherin in 75% and for cyclin D1 in 49% of the cells but were negative for vimentin in 13 out of 16 cases (81.3%). Tumors with aberrant p53 staining represented a non-significant higher vimentin but significantly higher cyclin D1 expression at the front of invasion than those with p53 wild-type pattern.!##!Conclusion!#!The present study shows no differences in the expression of EMT markers between node positive and node negative vulvar cancers. The evaluation of immunostaining within the micro-anatomical context indicates that an EMT-phenotype is restricted to the tumor cells at the front of invasion. Paired analyses of vulvar carcinomas and their lymph node deposits suggest mesenchymal-epithelial transition (MET) in the metastatic deposits. Immunohistochemical staining results may suggest that EMT is more prevalent in vulvar cancer with aberrant p53 staining

Demand for integrative medicine among women with breast and gynecological cancer: a multicenter cross-sectional study in Southern and Northern Germany

Purpose!#!The aim of this multicenter cross-sectional study was to analyze a cohort of breast (BC) and gynecological cancer (GC) patients regarding their interest in, perception of and demand for integrative therapeutic health approaches.!##!Methods!#!BC and GC patients were surveyed at their first integrative clinic visit using validated standardized questionnaires. Treatment goals and potential differences between the two groups were evaluated.!##!Results!#!340 patients (272 BC, 68 GC) participated in the study. The overall interest in IM was 95.3% and correlated with older age, recent chemotherapy, and higher education. A total of 89.4% were using integrative methods at the time of enrolment, primarily exercise therapy (57.5%), and vitamin supplementation (51.4%). The major short-term goal of the BC patients was a side-effects reduction of conventional therapy (70.4%); the major long-term goal was the delay of a potential tumor progression (69.3%). In the GC group, major short-term and long-term goals were slowing tumor progression (73.1% and 79.1%) and prolonging survival (70.1% and 80.6%). GC patients were significantly more impaired by the side-effects of conventional treatment than BC patients [pain (p = 0.006), obstipation (< 0.005)].!##!Conclusion!#!Our data demonstrate a high overall interest in and use of IM in BC and GC patients. This supports the need for specialized IM counseling and the implementation of integrative treatments into conventional oncological treatment regimes in both patient groups. Primary tumor site, cancer diagnosis, treatment phase, and side effects had a relevant impact on the demand for IM in our study population