Identifying safe diagnostic algorithms for sentinel lymph node mapping in high-risk endometrial cancer: The SENTIREC-endo study.

INTRODUCTION: It is unclear if sentinel node (SLN) mapping can replace pelvic- (PLD) and paraaortic lymphadenectomy (PALD) for high-risk endometrial cancer (EC). A diagnostically safe surgical algorithm, taking failed mapping cases into account, is not defined. We aimed to investigate the diagnostic accuracy of SLN mapping algorithms in women with exclusively high-risk EC. METHODS: We undertook a prospective national diagnostic cohort study of SLN mapping in women with high-risk EC from March 2017 to January 2023. The power calculation was based on the negative predictive value (NPV). Women underwent SLN mapping, PLD and PALD besides removal of suspicious and any FDG/PET-positive lymph nodes. Accuracy analyses were performed for five algorithms. RESULTS: 170/216 included women underwent SLN mapping, PLD and PALD and were included in accuracy analyses. 42/170 (24.7%) had nodal metastasis. The algorithm SLN and PLD in case of failed mapping, demonstrated a sensitivity of 86% (95% CI 74-100) and an NPV of 96% (95% CI 91-100). The sensitivity increased to 93% (95% CI 83-100) and the NPV to 98% (95% CI 94-100) if PLD was combined with removal of any PET-positive lymph nodes. Equivalent results were obtained if PLD and PALD were performed in non-mapping cases; sensitivity 93% (95% CI 83-100) and NPV 98% (95% CI 95-100). CONCLUSION: SLN-mapping is a safe staging procedure in women with high-risk EC if strictly adhering to a surgical algorithm including removal of any PET-positive lymph nodes independent of location and PLD or PLD and PALD in case of failed mapping.

Patient-initiated follow-up in women with early-stage endometrial cancer: A long-term follow-up of the OPAL trial.

OBJECTIVE: A long-term follow-up of the OPAL trial to compare the effect of patient-initiated (PIFU) versus hospital-based (HBFU) follow-up on fear of cancer recurrence (FCR), quality of life (QoL) and healthcare use after 34 months of follow-up. DESIGN: Pragmatic, multicentre randomised trial. SETTING: Four Danish departments of gynaecology between May 2013 and May 2016. POPULATION: 212 women diagnosed with stage I low-intermediate risk endometrial carcinoma. METHODS: The control group attended HBFU with regular outpatient visits (i.e., 8) for 3 years after primary treatment. The intervention group underwent PIFU with no prescheduled visits but with instructions about alarm symptoms and options of self-referral. MAIN OUTCOME MEASURES: The endpoints were FCR as measured by the Fear of Cancer Recurrence Inventory (FCRI) and QoL as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire C-30 (EORTC QLQ C-30), and healthcare use as measured by questionnaires and chart reviews after 34 months of follow-up. RESULTS: FCR decreased from baseline to 34 months in both groups and no difference was found between allocations (difference -6.31 [95% confidence interval -14.24 to 1.63]). QoL remained stable with no difference in any domains between the two arms at 34 months using a linear mixed model analysis. The use of healthcare was significantly lower in the PIFU group (P < 0.01). CONCLUSION: Patient-initiated follow-up is a valid alternative to hospital-based follow-up for people who have been treated for endometrial cancer and have low risk of recurrence.

The SENTIREC-endo study - Risks and benefits of a national adoption of sentinel node mapping in low and intermediate risk endometrial cancer.

OBJECTIVE: The SENTIREC-endo study aims to investigate risks and benefits of a national protocolled adoption of sentinel lymph node (SLN) mapping in women with early-stage low-grade endometrial cancer (EC) with low- (LR) and intermediate-risk (IR) of lymph node metastases. METHODS: We performed a national multicenter prospective study of SLN-mapping in women with LR and IR EC from March 2017-February 2022. Postoperative complications were classified according to Clavien-Dindo. Lymphedema was assessed as a change score and as incidence of swelling and heaviness evaluated by validated patient-reported outcome measures at baseline and three months postoperatively. RESULTS: 627 women were included in the analyses; 458 with LR- and 169 with IR EC. The SLN detection rate was 94.3% (591/627). The overall incidence of lymph node metastases was 9.3% (58/627); 4.4% (20/458) in the LR- and 22.5% (38/169) in the IR group. Ultrastaging identified 62% (36/58) of metastases. The incidence of postoperative complications was 8% (50/627) but only 0.3% (2/627) experienced an intraoperative complication associated with the SLN procedure. The lymphedema change score was below the threshold for clinical importance 4.5/100 CI: (2.9-6.0), and the incidence of swelling and heaviness was low; 5.2% and 5.8%, respectively. CONCLUSION: SLN mapping in women with LR and IR EC carries a very low risk of early lymphedema and peri- and postoperative complications. The national change in clinical practice contributed to a more correct treatment allocation for both risk groups and thus supports further international implementation of the SLN technique in early stage, low grade EC.

[Robotic surgery has been widely adopted within gynaecology in Denmark].

Gynaecologic robot-assisted laparoscopic surgery (RALS) is adopted in all Danish regions. It is primarily used in gynaecologic oncology but is increasingly introduced in benign surgery as well. Today > 90% of Danish women with early-stage endometrial cancer undergo minimally invasive surgery, primarily RALS. There is evidence that RALS has a short learning curve and is feasible even in complex surgical cases with a very low risk of conversion to open surgery. This review concludes that the increasing use of RALS in gynaecology calls for early, systematic, and practical education and training in robotics for future gynaecological fellows.

SENTIREC - The sentinel node mapping in women with cervical cancer study - Patient-reported early lymphedema and its impact on quality of life.

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.

From FIGO-2009 to FIGO-2018 in women with early-stage cervical cancer; Does the revised staging reflect risk groups?

OBJECTIVES: We aimed to evaluate if the revised staging according to FIGO-2018 in early-stage cervical cancer correctly predicts the risk for nodal metastases. METHODS: We reallocated 245 women with early-stage cervical cancer from FIGO-2009 to FIGO-2018 stages using data from a national, prospective cohort study on sentinel lymph node (SLN) mapping. We used univariate and multivariate binary regression models to investigate the association between FIGO-2018 stages, tumor characteristics, and nodal metastases. RESULTS: Stage migration occurred in 54.7% (134/245) (95% CI 48.2-61.0), due to tumor size or depth of invasion (71.6%, 96/134) and nodal metastases (28.4%, 38/134). Imaging preoperatively upstaged 7.3% (18/245); seven had nodal metastatic disease on final pathology. Upstaging occurred in 49.8% (122/245) (95% CI 43.4-56.2%) and downstaging to FIGO-2018 IA stages in 4.9% (12/245) (95% CI 2.6-8.4). The tumor size ranged from 3.0-19.0 mm in women with FIGO-2018 IA tumor characteristics, and none of the 14 women had nodal metastases. In multivariate analysis, risk factors significantly associated with nodal metastases were FIGO-2018 ≥ IB2 (RR 5.01, 95% CI 2.30-10.93, p < 0.001), proportionate depth of invasion >2/3 (RR 1.88, 95% CI 1.05-3.35, p = 0.033), and lymphovascular space invasion (RR 5.56, 95% CI 2.92-10.62, p < 0.001). CONCLUSIONS: The FIGO-2018 revised staging system causes stage migration for a large proportion of women with early-stage cervical cancer. Women who were downstaged to FIGO-2018 IA stages did not have nodal metastatic disease. The attention on depth of invasion rather than horizontal dimension seems to correctly reflect the risk of nodal metastases.

Sentinel lymph node mapping in early-stage cervical cancer - A national prospective multicenter study (SENTIREC trial).

OBJECTIVES: Sentinel lymph node (SLN) mapping may replace staging radical pelvic lymphadenectomy in women with early-stage cervical cancer. In a national multicenter setting, we evaluated SLN mapping in women with early-stage cervical cancer and investigated the accuracy of SLN mapping and FDG-PET/CT in tumors >20 mm. METHODS: We prospectively included women with early-stage cervical cancer from March 2017-January 2021 to undergo SLN mapping. Women with tumors >20 mm underwent completion pelvic lymphadenectomy and removal of FDG-PET/CT positive nodes. We determined SLN detection rates, incidence of nodal disease, sensitivity and negative predictive value (NPV) of SLN mapping, and the sensitivity, specificity, NPV, and positive predictive value (PPV) of FDG-PET/CT. RESULTS: We included 245 women, and 38 (15.5%) had nodal metastasis. The SLN detection rate was 96.3% (236/245), with 82.0% (201/245) bilateral detection. In a stratified analysis of 103 women with tumors >20 mm, 27 (26.2%) had nodal metastases. The sensitivity of SLN mapping adhering to the algorithm was 96.3% (95% CI 81.0-99.9%) and the NPV 98.7% (95% CI 93.0-100%). For FDG-PET/CT imaging the sensitivity was 14.8% (95% CI 4.2-33.7%), the specificity 85.5% (95% CI 75.6-92.5%), the NPV 73.9% (95% CI 63.4-82.7%), and the PPV 26.7% (95% CI 7.8-55.1%). CONCLUSIONS: SLN mapping seems to be an adequate staging procedure in early-stage cervical cancer tumors ≤20 mm. In tumors >20 mm, SLN mapping is highly sensitive but demands full adherence to the SLN algorithm. We recommend completion pelvic lymphadenectomy in tumors >20 mm until the oncological safety is established. FDG-PET/CT for nodal staging of women with early-stage cervical cancer seems limited.

Post robotic investment: Cost consequences and impact on length of stay for obese women with endometrial cancer.

INTRODUCTION: The aim of the study was to investigate whether robotic-assisted surgery is associated with lower incremental resource use among obese patients relative to non-obese patients after a Danish nationwide adoption of robotic-assisted surgery in women with early-stage endometrial cancer. This is a population-based cohort study based on registers and clinical data. MATERIAL AND METHODS: All women who underwent surgery (robotic, laparoscopic and laparotomy) from 2008 to 2015 were included and divided according to body mass index (<30 and ≥30). Robotic-assisted surgery was gradually introduced in Denmark (2008-2013). We compared resource use post-surgery in obese vs non-obese women who underwent surgery before and after a nationwide adoption of robotic-assisted surgery. The key exposure variable was exposure to robotic-assisted surgery. Clinical and sociodemographic data were linked with national register data to determine costs and bed days 12 months before and after surgery applying difference-in-difference analyses. RESULTS: In total, 3934 women were included. The adoption of robotic-assisted surgery did not demonstrate statistically significant implications for total costs among obese women (€3,417; 95% confidence interval [CI] -€854 to €7,688, p = 0.117). Further, for obese women, a statistically significant reduction in bed days related to the index hospitalization was demonstrated (-1.9 bed days; 95% CI -3.6 to -0.2, p = 0.025). However, for non-obese women, the adoption of robotic-assisted surgery was associated with statistically significant total costs increments of €9,333 (95% CI €3,729-€1,4936, p = 0.001) and no reduction in bed days related to the index hospitalization was observed (+0.9 bed days; 95% CI -0.6 to 2.3, p = 0.242). CONCLUSIONS: The national investment in robotic-assisted surgery for endometrial cancer seems to have more modest cost implications post-surgery for obese women. This may be partly driven by a significant reduction in bed days related to the index hospitalization among obese women, as well as reductions in subsequent hospitalizations.

Trends in Hysterectomy Incidence Rates During 2000-2015 in Denmark: Shifting from Abdominal to Minimally Invasive Surgical Procedures.

BACKGROUND: 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 in rates of benign hysterectomy (AAPC -2.1; 95% CI -2.7;-1.6). Irrespective of indication, rates of abdominal hysterectomy declined substantially during the study period and were surpassed by rates of minimally invasive procedures (ie, laparoscopy and robot-assisted laparoscopy) in 2013. CONCLUSION: Hysterectomy-corrected incidence rates of benign hysterectomy declined over time. Irrespective of indication, we observed a shift in surgical procedure over time, from abdominal hysterectomy to minimally invasive surgical procedures.

Sentinel lymph node mapping for endometrial and cervical cancer in Denmark.

INTRODUCTION: This was a surgical pilot study to systematically introduce the technique of sentinel lymph node (SLN) mapping in women with early-stage stage cervical cancer (CC) and endometrial cancer (EC) in Denmark. The study aimed to facilitate structured surgical training to ensure surgeon proficiency in SLN mapping. The study precedes two national prospective studies on the oncological safety and correct patient selection for SLN mapping in CC and EC. METHODS: The study was conducted at four gynaecological cancer centres at Odense and Aarhus University Hospital, Rigshospitalet and Herlev Hospital, between September 2016 and August 2019. All centres went through a protocolled introduction to the surgical technique, pelvic lymphatic drainage, pathological ultra-staging and data entry. A criterion of a total (uni- and bilateral) SLN detection of > 80%, based on 30 SLN mappings was set. RESULTS: The four centres performed 140 (range: 30-46) procedures. The total SLN detection rate was 91.3% with bilateral SLN detection in 68.8% and unilateral SLN detection in 22.5% of cases. The cumulated total SLN detection rate at three centres was above the pre-set 80% criterion from the beginning of inclusion, whereas one centre reached the criterion after 20 procedures. CONCLUSIONS: In this study, all centres demonstrated international-level SLN detection rates within 30 procedures. Hence, all centres met the study criterion regarding surgeon proficiency and were eligible for the national studies. FUNDING: Eva and Henry Frænkels Fond, Frimodt-Heineke Fonden, Kong Christian X Fond. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (R. no.15/52037). The SENTIREC studies including this pilot study are registered with clinicaltrials.gov (NCT02825355 and NCT02820506).

Identification of endometrial cancer recurrence - a validated algorithm based on nationwide Danish registries.

INTRODUCTION: Recurrence of endometrial cancer is not routinely registered in the Danish national health registers. The aim of this study was to develop and validate a register-based algorithm to identify women diagnosed with endometrial cancer recurrence in Denmark to facilitate register-based research in this field. MATERIAL AND METHODS: We conducted a cohort study based on data from Danish health registers. The algorithm was designed to identify women with recurrence and estimate the accompanying diagnosis date, which was based on information from the Danish National Patient Registry and the Danish National Pathology Registry. Indicators of recurrence were pathology registrations and procedure or diagnosis codes suggesting recurrence and related treatment. The gold standard for endometrial cancer recurrence originated from a Danish nationwide study of 2612 women diagnosed with endometrial cancer, FIGO stage I-II during 2005-2009. Recurrence was suspected in 308 women based on pathology reports, and recurrence suspicion was confirmed or rejected in the 308 women based on reviews of the medical records. The algorithm was validated by comparing the recurrence status identified by the algorithm and the recurrence status in the gold standard. RESULTS: After relevant exclusions, the final study population consisted of 268 women, hereof 160 (60%) with recurrence according to the gold standard. The algorithm displayed a sensitivity of 91.3% (95% confidence interval (CI): 85.8-95.1), a specificity of 91.7% (95% CI: 84.8-96.1) and a positive predictive value of 94.2% (95% CI: 89.3-97.3). The algorithm estimated the recurrence date within 30 days of the gold standard in 86% and within 60 days of the gold standard in 94% of the identified patients. DISCUSSION: The algorithm demonstrated good performance; it could be a valuable tool for future research in endometrial cancer recurrence and may facilitate studies with potential impact on clinical practice.

Relationship between a uterine fibroid diagnosis and the risk of adverse obstetrical outcomes: a cohort study.

OBJECTIVE: The aim was to investigate the association between clinically significant uterine fibroids and preterm birth, caesarean section (CS), postpartum haemorrhage (PPH), placental abruption, intrauterine growth restriction (IUGR) and uterine rupture. METHODS, PARTICIPANTS AND SETTING: A historical cohort study based on data from the Danish National Birth Cohort, the Danish National Patient Registry and the Danish National Birth Registry (DNBR). The final study population consisted of 92 696 pregnancies and was divided into four groups for comparison. Group 1: pregnancies of women without a fibroid diagnosis code or fibroid operation code; group 2: pregnancies of women with a fibroid diagnosis code before pregnancy, during pregnancy or up to 1 year after delivery, and no fibroid operation code before pregnancy; group 3: pregnancies of women with a fibroid diagnosis code given more than 1 year after delivery; and group 4: pregnancies of women with a fibroid operation code given before pregnancy. RESULTS: A diagnosis of fibroids before pregnancy yielded an increased risk of preterm birth (gestational age (GA) ≤37 weeks) (OR 2.27 (1.30─3.96)) and extreme preterm birth (GA 22+0─27+6 weeks, OR 20.09 (8.04─50.22)). The risk of CS was increased (OR 1.83 (1.23─2.72)) for women with a fibroid diagnosis code given before pregnancy; significantly increased risk of elective CS (OR 1.92 (1.11─3.32)), but not acute CS (OR 1.54 (0.94─2.52)). The risks of PPH, placental abruption or IUGR were not increased in any of the groups. CONCLUSION: We found a strong association between clinically significant uterine fibroids and preterm birth, and an association between clinically significant uterine fibroids and CS. In contrast, no association between clinically significant uterine fibroids and PPH, placental abruption or IUGR was seen.

Clinical impact of pre-treatment FDG-PET/CT staging of primary ovarian, fallopian tube, and peritoneal cancers in women.

INTRODUCTION: To assess the clinical impact of preoperative fludeoxyglucose (FDG) with positron emission tomography (PET) and computed tomography (CT) in women with ovarian, fallopian tube, or peritoneal cancer with focus on consequences of added findings (AFs). MATERIAL AND METHODS: FDG-PET/CT was implemented as a standard imaging modality for women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer at our institution in 2008. After full implementation, all preoperative scans were reviewed and AFs were evaluated from January 2011 to December 2012. Decisions regarding further examination made at the first multidisciplinary team conference were recorded. Subsequent procedures were tracked via medical records, and the impact of AFs on additional examinations, delay, and change in treatment plans was evaluated. RESULTS: Forty-four (21.1%) of 209 women presented with AFs. Further examination was performed in 35/44 (79.5%). Malignancy was identified in 15/35 (42.9%), revealing metastases from ovarian, fallopian tube, or peritoneal cancer in 11, a synchronous primary cancer in 3, and recurrence of a previous cancer in 1 woman. The ovarian, fallopian tube, or peritoneal cancer metastases were localized in the lungs, uterus, colon, vagina, and breasts. The remaining 20 AFs revealed 2 benign lesions and 1 pre-malignant lesion, whereas no abnormality was found in 17. Further examination of AFs resulted in a significant time delay until treatment start of median 4 days (range 1-83 days, P < 0.004). CONCLUSIONS: Further examinations of AFs by FDG-PET/CT delayed time to start of treatment by median 4 days in women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer in a contemporary institution with fast-track access to additional diagnostics. The clinical implications of this must be balanced against the gain of detecting unrecognized malignancy in 15 of 209 women (7.2%).

Uterine fibroids increase time to pregnancy: a cohort study.

Objectives: The primary purpose of the study was to investigate a possible association between uterine fibroids and time to pregnancy (TTP), and, secondly, to explore the effect of myomectomy on TTP.Methods: This historical cohort study used data from the Danish National Birth Cohort and the Danish National Patient Registry. The study population consisted of 86,323 women with 92,696 pregnancies. The main outcome was TTP; groups were compared using a binary outcome: TTP >12 months or TTP ≤12 months.Results: Women who had a fibroid diagnosis code before attempting to conceive (n = 92) had an increased risk of TTP >12 months compared with women without a fibroid diagnosis code (n = 87,358) (adjusted odds ratio [OR] 1.67; 95% confidence interval [CI] 1.05, 6.68). Women who had a fibroid diagnosis code after pregnancy (n = 963) also had an increased risk of TTP >12 months compared with women without a fibroid diagnosis code (adjusted OR 1.24; 95% CI 1.04, 1.47).Conclusion: We found an association between having a uterine fibroid diagnosis code and TTP >12 months. We were not able to make a valid assessment of the effect of myomectomy on TTP.

Long term resource consequences of a nationwide introduction of robotic surgery for women with early stage endometrial cancer.

OBJECTIVE: The majority of cost-studies related to robotic surgery has a short follow-up and primarily report the costs from the index surgery. The aim of this study was to evaluate the long-term resource consequences of introducing robotic surgery for early stage endometrial cancer in Denmark. METHODS: The study included all women with early stage endometrial cancer who underwent robotic, laparoscopic and open access surgery from January 2008 to June 2015. Data was linked from national databases to determine resource consumption and costs from hospital treatments, outpatient contacts, primary health care sector visits, labor market affiliation and prescription of medication. Each patient was observed in a period of 12 months before- and after surgery. The key exposure variable was women who were exposed to robotic surgery compared to those who were not. RESULTS: A total of 4133 women underwent surgery for early stage endometrial cancer. The study found additional costs of $7309 (95% confidence interval [CI] 2100-11,620, P = 0.001) per patient in the group exposed to robotic surgery including long-term costs post-surgery compared to the non-exposed group (non-robotic group). When controlling for time trends, the introduction of robotic surgery did not reduce the number of bed days (mean diff -0.42, 95% CI -3.03-2.19, P = 0.752). CONCLUSIONS: The introduction of robotic surgery for early stage endometrial cancer did not generate any long-term cost savings. The additional costs of robotic surgery were primarily driven by the index surgery. Any reduction in bed days could be explained by time trends.

How Do We Follow Up Patients With Endometrial Cancer?

PURPOSE OF REVIEW: In this review, we present the existing evidence regarding follow-up care after endometrial cancer, including content of follow-up and type of provider. We furthermore discuss the future perspectives for follow-up care and research in the field. RECENT FINDINGS: Recently published randomized controlled trials show that nurse-led telephone follow-up and patient-initiated follow-up are feasible alternatives to routine hospital-based follow-up. No randomized or prospective study has evaluated the effect of routine follow-up on survival. Hence, current knowledge is derived from retrospective studies with the inherent risk of bias. The most important method for recurrence detection is a review of symptoms. There is no evidence to support a survival benefit from the use of routine physical examinations, additional tests, or imaging. One in three of the women attending hospital-based follow-up experience unmet needs, and alternative models for follow-up focused on survivorship care and empowerment should be tested.

Surgery Is Physically Demanding and Associated With Multisite Musculoskeletal Pain: A Cross-Sectional Study.

BACKGROUND: Performing surgery involves well-known risk factors for developing musculoskeletal pain. Multisite musculoskeletal pain has shown to have an even higher adverse impact on the individual. We examined prevalence and intensity of multisite musculoskeletal pain in surgeons and identified characteristics associated with two or more painful body sites. MATERIALS AND METHODS: Information on sociodemographic, work experience, work demands, health status, physical capacity, and prevalence and intensity of musculoskeletal pain were collected from an internet-based questionnaire in 284 surgeons. Descriptive statistics were used to report prevalence and intensity of musculoskeletal pain. A logistic regression model was conducted to assess the characteristics associated with multisite musculoskeletal pain. RESULTS: Musculoskeletal pain was reported by 93% of the surgeons and 77% experienced multisite pain. The reported median pain intensities ranged from 2 to 4. Multisite musculoskeletal pain was significantly associated with being a female surgeon (OR: 3.4; 95% CI: 1.5-7.4), physical work demands (OR: 1.5 95% CI: 1.2-1.7), work ability (OR: 3.4; 95% CI: 1.6-7.0), and feeling a sense of heaviness in the head/headache (OR:4.8; 95% CI: 2.0-11.5). In addition, 21%-40% of the surgeons who experienced multisite pain reported that pain influenced their work, leisure time, and sleep negatively. CONCLUSIONS: The observed high prevalence of multisite musculoskeletal pain and high pain intensities adds new knowledge to the emerging literature on surgeons' health. In addition, several characteristics, for example, work ability, were significantly associated with multiple pain sites. This is concerning as pain could ultimately shorten a surgeon's career. Therefore, it is pertinent to develop preventive and rehabilitating strategies.

Immune profiling and identification of prognostic immune-related risk factors in human ovarian cancer.

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 co-inhibitory 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-γ, IL-2, TNF-α, IL-17 and CD107a. Blocking the PD-1 receptor resulted in significantly increased release of IFN-γ 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.

Nationwide Introduction of Minimally Invasive Robotic Surgery for Early-Stage Endometrial Cancer and Its Association With Severe Complications.

Importance: Minimally invasive laparoscopic surgery (MILS) for endometrial cancer reduces surgical morbidity compared with a total abdominal hysterectomy. However, only a minority of women with early-stage endometrial cancer undergo MILS. Objective: To evaluate the association between the Danish nationwide introduction of minimally invasive robotic surgery (MIRS) and severe complications in patients with early-stage endometrial cancer. Design, Setting, and Participants: In this nationwide prospective cohort study of 5654 women with early-stage endometrial cancer who had undergone surgery during the period from January 1, 2005, to June 30, 2015, data from the Danish Gynecological Cancer Database were linked with national registers on socioeconomic status, deaths, hospital diagnoses, and hospital treatments. The women were divided into 2 groups; group 1 underwent surgery before the introduction of MIRS in their region, and group 2 underwent surgery after the introduction of MIRS. Women with an unknown disease stage, an unknown association with MIRS implementation, unknown histologic findings, sarcoma, or synchronous cancer were excluded, as were women who underwent vaginal or an unknown surgical type of hysterectomy. Statistical analysis was conducted from February 2, 2017, to May 4, 2018. Exposure: Minimally invasive robotic surgery, MILS, or total abdominal hysterectomy. Main Outcomes and Measures: Severe complications were dichotomized and encompassed death within 30 days after surgery and intraoperative and postoperative complications diagnosed within 90 days after surgery. Results: A total of 3091 women (mean [SD] age, 67 [10] years) were allocated to group 1, and a total of 2563 women (mean [SD] age, 68 [10] years) were allocated to group 2. In multivariate logistic regression analyses, the odds of severe complications were significantly higher in group 1 than in group 2 (odds ratio [OR], 1.39; 95% CI, 1.11-1.74). The proportion of women undergoing MILS was 14.1% (n = 436) in group 1 and 22.2% in group 2 (n = 569). The proportion of women undergoing MIRS in group 2 was 50.0% (n = 1282). In group 2, multivariate logistic regression analyses demonstrated that a total abdominal hysterectomy was associated with increased odds of severe complications compared with MILS (OR, 2.58; 95% CI, 1.80-3.70) and MIRS (OR, 3.87; 95% CI, 2.52-5.93). No difference was found for MILS compared with MIRS (OR, 1.50; 95% CI, 0.99-2.27). Conclusions and Relevance: The national introduction of MIRS changed the surgical approach for early-stage endometrial cancer from open surgery to minimally invasive surgery. This change in surgical approach was associated with a significantly reduced risk of severe complications.

Feeling lucky: hierarchies of suffering and stories of endometrial cancer in a Danish context.

Illness stories are a prime analytical way of understanding patient perspectives on cancer. Nevertheless, limited studies have focused on stories of endometrial cancer. An ethnographic study including participant observation and interviews among 18 Danish women with endometrial cancer was conducted to examine prevalent stories and the ways the women responded to them. In this article, the analysis focuses on two exemplary cases, which present a line of issues related to the kinds of experiences that suffering includes. Findings illustrate that feelings of luck were central to the experience of being diagnosed, treated and cured, which was related to the way health professionals framed endometrial cancer as favourable through notions of curable/incurable, trivial and gentle/invasive and brutal, and aggressive/non-aggressive. Drawing upon the concept of a 'hierarchy of suffering', we exemplify how women tended to scale own experiences of suffering against others', leading some to believe they were not in a legitimate position to draw attention to themselves nor seek help and support, despite adverse physical, psychosocial effects. Thus, feelings of being lucky were intertwined with a sense of ambivalence. We conclude by discussing how suffering arises within a moral context, suggesting that the ways we speak of cancer may make some experiences unspeakable. This calls for increased clinical attention to more diverse narratives of cancer.