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Objective: To evaluate patient-reported incidence and severity of early lymphedema and its impact on quality of life (QoL) after sentinel lymph node (SLN) mapping only and after SLN and pelvic lymphadenectomy (PL) in women undergoing surgery for early-stage cervical cancer.Methods: In a national prospective multicenter study, we included women with early-stage cervical cancer from March 2017-January 2021 to undergo radical surgery including SLN mapping. Women with tumors >20 mm underwent completion PL. The incidence and severity of early lymphedema and its influence on QoL were evaluated using validated patient-reported outcome measures before surgery and three months postoperative. We investigated changes over time using linear regression.Results: Two hundred of 245 (81.6%) included women completed questionnaires at baseline and three months postoperatively. The incidence of early lymphedema was 5.6% (95% CI 2.1-11.8%) and 32.3% (95% CI 22.9-42.7%) in women who underwent SLN mapping only and SLN + PL, respectively. Lymphedema symptoms in the legs, genitals, and groins increased in both groups postoperatively but three times more in women who underwent PL. Lymphedema symptoms after SLN + PL significantly impaired physical performance (p = 0.001) and appearance (p = 0.007). Reporting lymphedema was significantly associated with impaired body image, physical-, role-, and social functioning, and a high level of fatigue.Conclusions: SLN mapping alone carries a low risk of lymphedema in women undergoing surgery for early-stage cervical cancer. In contrast, completion PL is associated with a high incidence of early lymphedema. Reporting lymphedema is associated with significant impairment of several physical, psychological, and social aspects of QoL.

Kathrine Dyhr Lycke,1,2 Johnny Kahlert,3 Rikke Damgaard,1,2 Ole Mogensen,2,4 Anne Hammer1,2,4 1Department of Obstetrics and Gynecology, NIDO | Denmark, Gødstrup Hospital, Herning, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, DenmarkCorrespondence: Kathrine Dyhr LyckeDepartment of Obstetrics and Gynecology, NIDO | Denmark, Gødstrup Hospital, Gl. Landevej 61, Herning, DK-7400, DenmarkEmail katlyc@clin.au.dkBackground: Hysterectomy (removal of the uterus) is a common surgical procedure in gynecology. Although minimally invasive surgical procedures have been introduced, hysterectomy is still associated with risk of short- and long-term complications. Given that hysterectomized women are no longer at risk of either hysterectomy or being diagnosed with endometrial or cervical cancer, it is important to describe trends in hysterectomy rates.Objective: To describe trends in hysterectomy incidence rates overall and stratified by age, indication, and procedure.Methods: Nationwide population-based cohort study using Danish national registries, 2000– 2015, was conducted. We calculated the overall hysterectomy-corrected and age-standardized incidence rates of hysterectomy among women ≥ 20 years old. Incidence rates were stratified by age group, indication, and surgical procedure. We performed trend analyses using Joinpoint regression, thereby estimating the average annual percentage change (AAPC).Results: A total of 98,484 women had a hysterectomy during the study period, corresponding to an overall age-standardized, hysterectomy-corrected hysterectomy incidence rate (SIR) of 351.1 per 100,000 person-years (95% CI 348.9;353.3). SIR of hysterectomy declined over time (AAPC − 1.4; 95% CI − 1.9;-1.0), which was driven by a decline i

Suppression of immune reactivity by increased expression of co-inhibitory receptors has been discussed as a major reason as to why the immune system fails to control tumor development. Elucidating the co-inhibitory expression pattern of tumor-infiltrating lymphocytes in different cancer types will help to develop future treatment strategies. We characterized markers reflecting and affecting T-cell functionality by flow cytometry on lymphocytes isolated from blood, ascites and tumor from advanced ovarian cancer patients (n = 35). Significantly higher proportions of CD4+ and CD8+ T-cells expressed coinhibitory receptors LAG-3, PD-1 and TIM-3 in tumor and ascites compared to blood. Co-expression was predominantly observed among intratumoral CD8+ T-cells and the most common combination was PD-1 and TIM-3. Analysis of 26 soluble factors revealed highest concentrations of IP-10 and MCP-1 in both ascites and tumor. Correlating these results with clinical outcome revealed the proportion of CD8+ T-cells without expression of LAG-3, PD-1 and TIM-3 to be beneficial for overall survival. In total we identified eight immune-related risk factors associated with reduced survival. Ex vivo activation showed tumor-derived CD4+ and CD8+ T-cells to be functionally active, assessed by the production of IFN-gamma, IL-2, TNF-alpha, IL-17 and CD107a. Blocking the PD-1 receptor resulted in significantly increased release of IFN-. suggesting potential reinvigoration. The ovarian tumor environment exhibits an inflammatory milieu with abundant presence of infiltrating immune cells expressing inhibitory checkpoints. Importantly, we found subsets of CD8+ T-cells with double and triple expression of co-inhibitory receptors, supporting the need for multiple checkpoint-targeting agents to overcome T-cell dysfunction in ovarian cancer., QC 20190218

BACKGROUND: The Faroe Islands have had nationally organised cervical cancer screening since 1995. Women aged 25-60 years are invited every third year. Participation is free of charge. Although several European overviews on cervical screening are available, none have included the Faroe Islands. Our aim was to provide the first description of cervical cancer screening, and to determine the screening history of women diagnosed with cervical cancer in the Faroe Islands.MATERIAL AND METHODS: Screening data from 1996 to 2012 were obtained from the Diagnostic Centre at the National Hospital of the Faroe Islands. They included information on cytology and HPV testing whereas information on histology was not registered consistently. Process indicators were calculated, including coverage rate, excess smears, proportion of abnormal cytological samples, and frequency of HPV testing. Data on cervical cancer cases were obtained from the Faroese Ministry of Health Affairs. The analysis of the screening history was undertaken for cases diagnosed in 2000-2010.RESULTS: A total of 52 457 samples were taken in 1996-2012. Coverage varied between 67% and 81% and was 71% in 2012. Excess smears decreased after 1999. At present, 7.0% of samples have abnormal cytology. Of all ASCUS samples, 76-95% were tested for HPV. A total of 58% of women diagnosed with cervical cancer did not participate in screening prior to their diagnosis, and 32% had normal cytology in the previous four years.CONCLUSION: Despite the difficult geographical setting, the organised cervical cancer screening programme in the Faroe Islands has achieved a relatively high coverage rate. Nevertheless, challenges, e.g. consistent histology registration and sending reminders, still exist.

OBJECTIVE: To identify the extent of lymphadenectomy performed in women presenting with epithelial ovarian cancer macroscopically confined to the ovary. Furthermore, the effect of lymphadenectomy on overall survival is evaluated.DESIGN: A prospective nationwide case-only study.SETTING: Denmark 2005-2011.SAMPLE: All women registered in the nationwide Danish Gynecologic Cancer Database from 1 January 2005 to 1 May 2011, presenting with a tumor macroscopically confined to the ovary without visible evidence of abdominal spread at the time of the initial exploration (surgical stage I).METHOD: Descriptive and survival analyses of data from Danish Gynecologic Cancer Database.MAIN OUTCOME MEASURES: The annual proportion of women with surgical stage I disease who received lymphadenectomy and the survival in the two groups.RESULTS: Of 2361 women with epithelial ovarian cancer, 627 were identified with surgical stage I. Lymphadenectomy was performed in 216 women (34%) of whom 13 (6%) had lymph node metastases. At 5-year follow up 85% remained alive in the lymphadenectomy group compared with 80% in the control group (p = 0.064). The lymphadenectomy fraction increased from 24% in 2005 to 55% in 2011. When univariate and multivariate analyses were conducted only an insignificant difference in the survival probability was found between lymphadenectomy and no lymphadenectomy in women presenting with tumor macroscopically confined to the ovary.CONCLUSION: Although increasing, the number of women with surgical stage I disease in Denmark who receive lymphadenectomy remains low, but this did not seem to make a difference to survival.

Objective: The aim of this article is to present a new methodology to illustrate, understand, and measure delay in health care. The method is inspired by process mapping tools as analytical framework and demonstrates its usefulness for studying diagnostic delay in gynecological cancer. Materials and Methods: Six women with a diagnostic delay of 6 weeks or more before treatment of gynecological cancer at a specialized regional department (the Department of Gynecology and Obstetrics, Odense University Hospital, Denmark) were included in the study. Maps of existing processes were performed for each patient reflecting the patients' pathway through the course of the disease. We combined 2 process mapping tools, namely, value stream mapping and business process modeling notation. The first method identifies the flow in a process as timelines. The latter introduces a set of easily recognizable graphical elements. Results: Detailed information concerning the cancer patients' pathway was obtained. The method visualized the complexities within the diagnostic pathway. The role of different participants (patient, general practitioner, and local hospitals) became clear by arranging activities according to responsibilities and was shown to recurrently influence and contribute to the delay in the diagnostic process. Some important contributors to diagnostic delay in gynecological cancer, such as lack of cancer suspicion, competing diseases, negative test results, inexpedient referral patterns, and referrals without cancer suspicion, were found. Conclusions: Our results point out process mapping tools as a potential analytical framework to illustrate, understand, and measure delay in health care. Furthermore, the method was able to identify important contributors to the diagnostic delay in gynecological cancer patients.

Introduction: To describe the different delay types in women with gynecological cancer and to analyze the relationship between diagnostic delay and a number of characteristics for patients, cancers, and the health care system. Method: Data were obtained from 4 different questionnaires, the Electronic Patient Journal (EPJ), and the Danish Gynecological Cancer Database (DGCD). A total of 161 women with ovarian cancer (63), endometrial cancer (50), cervical cancer (34), and vulvar cancer (14) were included. Outcome measures were different delay types counted in days and 4 clinically important variables' impact on the diagnostic delay: presence of alarm symptoms, age (divided into 2 groups: ≤60 or >60 years), performance of gynecological examination by the general practitioner (GP), and notification of cancer suspicion on first referral from GP. Results: Across cancer types, median total delay was 101 days. Some 10% of women experienced the longest delay with a total delay of 436 days or more. Vulva cancer had the longest delay, whereas women with ovarian cancer had the shortest delay. More than one third (39%) of the women consulted their GP for reasons other than the predefined alarm symptoms. Gynecological examination by the GP was less likely to be performed if the woman did not present with vaginal bleeding. The length of the delay was shortened by performance of a gynecological examination by the GP and a primary referral from the GP raising the receiver's suspicion of cancer. Conclusion: Reducing diagnostic delays should be achievable, particularly for those most delayed, and interventions aimed at reducing delays need to be developed. Creation of new valid instruments for measuring delay is essential in future research.

Introduction: Lack of communication, care and respect from healthcare professionals can be challenges for patients in trajectories of cancer, possibly accompanied by experienced fragmentation of the care, anxiety and worries. One way to try to improve delivery of care is additional help from nurse navigators (NN) offered in a predefined shorter or longer period, but patients’ experiences with this have seldom been investigated. Aims: To explore experiences of nurse navigation offered in a short period of a longer subsequent part of cancer trajectories by patients who can use the help on offer. Methods: The NNs worked from one hospital department with patients in the transition between primary care and a university hospital before admission. A phenomenological-hermeneutical longitudinal study was performed from referral and until two months after discharge from the hospital. Semi-structured interviews with five patients who could use the help from an NN provided data for the analysis, which started open-minded. Results: Affectional bonds were made to the NN and patients felt that they benefited from her presence and her help, which they requested until one month after discharge. They were disappointed and felt rejected when the contact to the NN stopped. Conclusion: In efforts to increase quality of care for patients with cancer we recommend an increased awareness of cultural areas within the healthcare system, which may be an impediment to good communication. Moreover, we recommend paying special attention to critical periods in cancer patients’ trajectories, as well as to the theory of attachment to supplement thoughts of continuity of care and coordination in the care for women. In short, it is fine to offer additional help to those who can use it, but in practice as well as in research we recommend awareness of how and when to stop the help, to prevent patients from feeling hurt.

Elicitation techniques in connection with semi-structured interviews are scantily used, but reported to be beneficial to research. We developed and tested a new visual technique to be utilized in the latter part of semi-structured interviews. It has proved to be feasible and beneficial to use, and it could possibly be used by others. This way of extending the interviews generates more data in a visual form, as well as in a verbal form, by supporting the participants in remembering nearly forgotten parts of their experiences and in expressing emotions associated with those significant experiences. As a contribution to qualitative research, our study showed that the visual data, created by the participants, also contributed to getting the elaborated narratives.

To explore the extent of evidence-based data and cost-utility of follow-up after primary treatment of endometrial and ovarian cancer, addressing perspectives of technology, organization, economics, and patients.

Udgivelsesdato: 2009-Oct, The purpose was to find a gene expression profile that could distinguish short-term from long-term survivors in our collection of serous epithelial ovarian carcinomas. Furthermore, it should be able to stratify in an external validation set. Such a classifier profile will take us a step forward toward investigations for more individualized therapies and the use of gene expression profiles in the clinical practice. RNA from tumor tissue from 43 Danish patients with serous epithelial ovarian carcinoma (11 International Federation of Gynecology and Obstetrics [FIGO] stage I/II, 32 FIGO stage III/IV) was analyzed using Affymetrix U133 plus 2.0 microarrays. A multistep statistical procedure was applied to the data to find the gene set that optimally split the patients into short-term and long-term survivors in a Kaplan-Meier plot. A 14-gene prognostic profile with the ability to distinguish short-term survivors (median overall survival of 32 months) from long-term survivors (median overall survival not yet reached after a median follow-up of 76 months) with a P value of 3.4 x 10 was found. The prognostic gene set was also able to distinguish short-term from long-term survival in patients with advanced disease. Furthermore, its ability to classify in an external validation set was demonstrated. The identified 14-gene prognostic profile was able to predict survival (short- vs long-term survival) with a strength that is better than any other prognostic factor in epithelial ovarian cancer including FIGO stage. This stratification method may form the basis of determinations for new therapeutic approaches, as patients with poor prognosis could obtain the biggest advantage from new treatment modalities.

Udgivelsesdato: 2009-null, BACKGROUND: The epidermal growth factor (EGF) system comprises four receptors, HER1-4, and several ligands, and is cyclically expressed in endometrium from healthy fertile women. Our aim is to identify differences in expression of the EGF system between endometriotic and normal endometrium. METHODS: We previously examined the EGF system in endometrial samples from healthy women (n = 14). Here we examine samples from endometrium (n = 23), endometriomas (n = 10) and peritoneal endometriosis (n = 9) from women with endometriosis (n = 23). mRNA expression of receptors and ligands from the EGF system was analyzed by real-time PCR, and proteins were localized by immunohistochemistry. RESULTS: Endometrial mRNA for HER1-3 was high compared with our previous findings in healthy endometrium, whereas HER4 and the ligands were unchanged. Endometriomas show lower expression of HER1-3 and no HER4 expression. Significant differences were demonstrated in late secretory phase for HER1 and HER2 and in the proliferative phase for HER3 compared to healthy women. Immunohistochemically, HER2 was identified in all samples, predominately in glands and surface epithelium. In a few glands, HER2 was in both cytoplasm and cell membrane. CONCLUSION: We report quantitative and qualitative differences in the EGF system in endometriotic eutopic endometrium compared to endometrium from healthy individuals.

The Epidermal Growth Factor (EGF) system is expressed in healthy premenopausal endometrium. We describe the expression of the four receptors, HER1, HER2, HER3, HER4 and the six ligands amphiregulin, transforming growth factor alpha (TGF-alpha), heparin binding EGF like growth factor (HB-EGF), betacellulin, epiregulin and EGF in endometrioid endometrial cancer.