Has time to chemotherapy from primary debulking surgery in advanced ovarian cancer an impact on survival? - A population-based nationwide SweGCG study.

OBJECTIVE: The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). METHODS: Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008-2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; ≤21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. RESULTS: In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0-21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC ≤21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0-21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. CONCLUSIONS: For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS.

Gynecological cancer during pregnancy-From a gyne-oncological perspective.

Gynecological cancer diagnosed during pregnancy requires accurate diagnosis and staging to determine optimal treatment based on gestational age. Cervical and ovarian cancers are the most common and multidisciplinary team collaboration is pivotal. Magnetic resonance imaging and ultrasound can be used without causing fetal harm. In cervical cancer, early-stage treatments can often be delayed until fetal lung maturation and cesarean section is recommended if disease prevails, in combination with a simple/radical hysterectomy and lymphadenectomy. Chemoradiotherapy, the recommended treatment for advanced stages, is not compatible with pregnancy preservation. Most gestational ovarian cancers are diagnosed at an early stage and consist of nonepithelial cancers or borderline tumors. Removal of the affected adnexa during pregnancy is often necessary for diagnosis, though staging can be performed after delivery. In selected cases of advanced cervical and ovarian cancers, neoadjuvant chemotherapy may be an option to allow gestational advancement but only after thorough multidisciplinary discussions and counseling.

Long-term health-related quality-of-life and psychosocial outcomes after uterus transplantation: a 5-year follow-up of donors and recipients.

STUDY QUESTION: What are the outcomes regarding health-related quality-of-life, mood, and marital relationship of recipients and donors 5 years after uterus transplantation (UTx) and uterus donation? SUMMARY ANSWER: Both recipients and donors generally demonstrated long-term stability regarding psychosocial outcomes but with negative deviations associated with unsuccessful outcomes. WHAT IS KNOWN ALREADY: UTx is the first infertility treatment for women with absolute uterine factor infertility. The procedure can be performed with either a uterus donation from a live donor (LD), typically a close relative, or from a deceased, multi-organ donor. There are many potential stressful events over several years after UTx both for recipients and for LDs and these events may have impacts on quality-of-life and mental well-being. STUDY DESIGN, SIZE, DURATION: This, prospective observational cohort study includes the nine recipients and LDs of the first human UTx trial. They were assessed in 2017-2018 by questionnaires 5 years after UTx. PARTICIPANTS/MATERIALS, SETTING, METHODS: The nine recipients (ages 32-43 years) and their respective LDs (ages 44-67 years) were either related (n = 8) or friends (n = 1). Eight recipients had congenital uterine absence and one was hysterectomized due to cervical cancer. For two recipients, UTx resulted in early graft failures, while six of the other seven recipients gave birth to a total of eight babies over the following 5 years. Physical and mental component summaries of health-related quality-of-life were measured with the SF-36 questionnaire. Mood was assessed by the Hospital Anxiety and Depression Scale. Relationship with partner was measured with the Dyadic Adjustment Scale. Comparisons were made between the values after 5 years and the values before uterus donation/transplantation. MAIN RESULTS AND THE ROLE OF CHANCE: Five years after primary UTx, the majority of recipients scored above the predicted value of the general population on quality-of-life, except for two women, one of whom had a viable graft but no live birth and one recipient who was strained by quality-of-life changes, possibly related to parenthood transitions. Regarding mood, only one value (anxiety) was above the threshold for further clinical assessment. Recipients showed declining satisfaction with their marital relationships, but all reported scores above the 'at risk for divorce' threshold at the time of the final assessment in our study. The LDs were all found to be stable and above the predicted value of the general population regarding mental components of quality-of-life. Three LDs showed declined physical components, possibly related to older age. Only one LD reported a value in mood (anxiety) that would need further assessment. The marital satisfaction of LDs remained stable and unchanged compared to baseline values. Notably, the two recipients with early graft failures, and their related LDs, regained their mental well-being during the first years after graft failure and remained stable after 5 years. LIMITATIONS, REASONS FOR CAUTION: The restricted sample size and the single-centre study-design are limitations of this study. Additionally the study was limited to LD UTx, as opposed to deceased donor UTx. WIDER IMPLICATIONS OF THE FINDINGS: Our study shows that both LDs and recipients had acceptable or favourable quality-of-life outcomes, including mood assessment, at the 5-year follow-up mark, and that failure to achieve a live birth negatively affected these modalities both for LDs and recipients. Moreover, an important finding was that LDs and recipients are not reacting with depression after hysterectomy, which is common after hysterectomy in the general population. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the Jane and Dan Olsson Foundation for Science, Knut and Alice Wallenberg Foundation, Handlanden Hjalmar Svensson Foundation, Swedish Governmental ALF Grant, and Swedish Research Council. There are no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: NCT01844362.

A federated approach to identify women with early-stage cervical cancer at low risk of lymph node metastases.

OBJECTIVE: Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection. METHODS: Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion criteria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+. RESULTS: We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59-5.79), tumour size 21-40 mm (OR 2.14, 95% CI, 1.89-2.43) and depth of invasion>10 mm (OR 1.81, 95% CI, 1.59-2.08). A group of 1469 women (41%)-with tumours without LVSI, tumour size ≤20 mm, and depth of invasion ≤10 mm-had a very low risk of pN+ (2.4%, 95% CI, 1.7-3.3%). CONCLUSION: Early-stage cervical cancer without LVSI, a tumour size ≤20 mm and depth of invasion ≤10 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.

Health-related quality of life after robotic surgery for endometrial cancer: a prospective longitudinal one-year follow-up study.

PURPOSE: This study aimed to explore how patients treated for endometrial cancer (EC) with robotic surgery are affected in symptoms of anxiety and depression and HRQoL in the long term. METHODS: Women scheduled for primary robotic surgery for EC were included (n = 64), in this single-center study. Socioeconomic variables were obtained at baseline. The European Organization for Research and Treatment of Cancers Quality of Life Questionnaire Core 30 (QLQ-C30), its module for EC (EN24), the Generalized Anxiety Disorder Scale (GAD-7), and the Patient Health Questionnaire Depression Scale (PHQ-9) were followed prospectively from baseline to 2 weeks, 3 months and 1 year postoperatively. RESULTS: The number of patients scoring above the clinical threshold for anxiety decreased from 17 (27.0%) at baseline to 4 (7.0%) at 2 weeks (p = 0.012). Depressive symptoms were reported in 20% of patients at baseline and did not change significantly during the one-year follow-up (p = 0.58). A significant decrease in Global health status was seen at 2 weeks (from 69.8 to 62.7; p = 0.048), with return to baseline levels after 3 months (68.5; p = 0.32) and stable at 1 year. Unemployment, low income, and adjuvant therapy correlated with lower Global health status at 3 months. CONCLUSION: The significant proportion of patients with anxiety symptoms preoperatively reduced prompt after surgery, while the proportion with depression remained constant, indicating that the primary treatment has no long-term negative effect on patients' mental health. At 3 months, there is no obvious remaining negative impact on patients' HRQoL, and these results are consistent after 1 year.

Recurrence and survival in endometrioid endometrial cancer - a population-based cohort study.

OBJECTIVE: The aim of this study was to investigate recurrences and survival in endometrioid endometrial cancer (EC) in a complete population-based cohort. METHODS: A regional population-based study including women with endometrioid EC, identified by the Swedish Quality Registry for Gynecological Cancer (SQRGC), where primary surgery was performed between 2010 and 2017. Patient characteristics and outcomes, including recurrences, were retrieved from the SQRGC and completed by records reviews. Overall (OS), net (NS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. The Fine and Gray proportional subdistribution hazards' regression model was used for risk factors for recurrence. RESULTS: There were 1630 women included in the study, whereof 136 (8.3%) had a recurrence with a median time to recurrence of 22.5 months (range 3.2-59.3). One site of recurrence was diagnosed in 69.1%, while 27.2% being only vaginal. The total 5-year OS was 88.0%(95% CI:86.4-89.7) and the 5-year NS 98.6%(95% CI:96.5-100.7). If no recurrence occurred, the OS was 91.9%(95% CI:90.4-93.3) and NS 102.8%(95% CI:100.9-104.8). For only vaginal recurrence, 5-year OS was 77.0%(95% CI:64.0-92.6) compared to 36.1%(95% CI:27.5-47.3) for all other recurrences. The total 5-year DFS was 83.9%(95% CI:82.0-85.7). In the multivariable analysis, age, FIGO stage and primary treatment were found independent factors for recurrence with a HR of 1.29(95% CI:1.11-1.51;p = 0.001) for age, 2.78(95% CI:1.80-4.29;p < 0.001) for FIGO stage III and 1.84(95% CI:1.22-2.78;p 0.004) for adjuvant treatment. CONCLUSION: There is an overall low recurrence rate for endometrioid ECs with a minor portion being only vaginal, associated with a favorable survival in contrast to other recurrences with a poor prognosis. Age, FIGO stage III and adjuvant treatment were found independent prognostic factors for recurrence.

Registry of the International Society of Uterus Transplantation: First Report.

BACKGROUND: Uterus transplantation (UTx) is a novel type of transplantation to treat infertility in women with an absent or nonfunctioning uterus. The International Society of Uterus Transplantation (ISUTx) has developed a registry to monitor worldwide UTx activities while serving as a repository for specific research questions. METHODS: The web-based registry has separate data fields for donor, recipient, surgeries, immunosuppression, rejections, pregnancies with live birth(s), and transplant hysterectomies. Data are prospectively registered. RESULTS: A total of 45 UTx procedures have been registered; the majority (78%) of those procedures were live donor (LD) transplants. Median age of the LDs, deceased donors, and recipients were 50 y (range 32-62), 38.5 y (19-57), and 29 y (22-38), respectively. The duration of LD surgery was approximately twice as long as the recipient surgery. Postoperative complications of any Clavien-Dindo grade were registered in 20% of LDs and 24% of recipients. Rejection episodes were more frequent (33%) early after transplantation (months 1-5) compared with later time points (months 6-10; 21%). Healthy neonates were delivered by 16 recipients, with 3 women giving birth twice. The total live birth rate per embryo transfer was 35.8%. Median length of pregnancy was 35 gestational weeks. Twelve uteri were removed without childbirth, with 9 transplant hysterectomies occurring during the initial 7 mo post-UTx. CONCLUSIONS: A mandatory registry is critical to determine quality and process improvement for any novel transplantation. This registry provides a detailed analysis of 45 UTx procedures performed worldwide with a thorough analysis of outcomes and complications.

Societal costs of ovarian cancer in a population-based cohort - a cost of illness analysis.

BACKGROUND: The societal cost associated with ovarian cancer (OC) is not well known. Increasing costs for new treatments and/or the impact of organizational changes motivates these costs to be described and communicated. This study aims to evaluate the cost of illness of OC in a population-based cohort. MATERIAL AND METHODS: All patients diagnosed with ovarian, fallopian tube, primary peritoneal cancer, and serous cancer of undesignated primary site (UPS) in 2011-2012 were followed for six years. Direct costs, i.e., costs for health care expenditures, were gathered from the regional healthcare database. Information on indirect costs, i.e., costs of loss of production due to sick leave, was retrieved from Statistics Sweden. Sub-group analyses were conducted regarding stage, income levels, residential area, and diagnosis. RESULTS: The cost of illness for all stages during the six years of follow-up was €201,086 per patient, where indirect costs constituted 43.7%. The mean cost of illness per year per patient for all stages was €33,514. Direct costs were higher in advanced stages compared to early stages for every year from diagnosis. During the first two years, there were no differences in indirect costs between early and advanced stages. However, during the third year there was a difference with higher indirect costs in advanced stages. There was no difference in direct costs depending on income levels. Regarding residential area, there was a difference in the outpatient cost during the index and second year with higher costs when chemotherapy and follow-up were provided at county hospitals, compared to at the tertiary hospital. CONCLUSIONS: Indirect costs constituted a large part of the cost of illness over 6 years from diagnosis. This could indicate that even though treatment costs can be expected to rise with the introduction of new therapies, the societal cost may decrease when survival increase.

Hormone replacement in premenopausal women treated with bilateral oophorectomy for ovarian cancer - a nationwide population-based study.

OBJECTIVE: To study the extent of hormone replacement therapy (HRT) dispensing in premenopausal women after being treated with bilateral salpingo-oophorectomy (BSOE) for ovarian cancer (OC). METHODS: Nationwide population- and register-based cohort study including women 18-50 years old, registered in The Swedish Quality Register for Gynecological Cancer (SQRGC), where BSOE was performed due to epithelial (EOC) and non-epithelial ovarian cancers (NEOC) or borderline ovarian tumor (BOT) between 2008 and 2014. Data on HRT dispensing was obtained from the National Prescribed Drug Register analyzed at semi-annual intervals from surgery until end of follow-up December 2015, including a logistic regression analysis. RESULTS: A cohort of 664 women were identified with OC, whereas 396 women had an EOC, 61 a NEOC and 207 a BOT. At surgery 49% of the women were ≤44 years. HRT dispensed to the total cohort varied between 32% and 41% the first five years after surgery. During follow-up at first 0.5-1 year 51% of the women <40 years were dispensed HRT compared to 25% of women ≥40 years. Of women with EOC, 21% dispensed HRT at first 0.5-1 year. In the multivariable regression analysis; age <40 (OR6.17, p < 0.001) and age 40-44 (OR2.95, p < 0.001) as well as BOT histology (OR3.84, p < 0.001) were found significant variables for dispensing of HRT. CONCLUSION: A majority of premenopausal women undergoing BSOE for OC did not use HRT postoperatively. Our study shows that there is a need to address HRT use after OC treatment in young women to prevent from morbidity and a poorer quality of life.

Evolving clinical challenges in uterus transplantation.

Before the first live birth following uterus transplantation (UTx) in 2014, the 1-2% of women with an absent or non-functional uterus had no hope of childbearing. With 64 cases of UTx and 34 births reported in the scientific literature, this emerging technology has the potential for translation into mainstream clinical practice. However, limitations currently include donor availability, recipient suitability, surgical challenges regarding success and complications, and recipient management after UTx and during pregnancy. This review considers these challenges and ways to overcome them so that UTx could become part of the reproductive specialist's armamentarium when counselling patients with uterine factor infertility.

Case Report: Post-Partum SARS-CoV-2 Infection After the First French Uterus Transplantation.

Absolute uterus factor infertility, whether congenital or acquired, renders the woman unable to carry a child. Although uterus transplantation (UTx) is being increasingly performed as a non-vital procedure to address this unfortunate condition, the immunosuppression required presents risks that are further compounded by pregnancy and during the puerperium period. These vulnerabilities require avoidance of SARS-CoV-2 infection in pregnant UTx recipients especially during the third trimester, as accumulating evidence reveals increased risks of morbidity and mortality. Here we describe a successful UTx case with delivery of a healthy child, but in which both mother and neonate developed asymptomatic SARS-CoV-2 infection seven days after RNA vaccination, on day 35 post-partum. Although the patient was successfully treated with a combination therapy comprised of two monoclonal antibodies, this case highlights the challenges associated with performing UTx in the era of Covid-19. More broadly, the risks of performing non-vital organ transplantation during a pandemic should be discussed among team members and prospective patients, weighing the risks against the benefits in improving the quality of life, which were considerable for our patient who achieved motherhood with the birth of a healthy child.

Reproductive, obstetric, and long-term health outcome after uterus transplantation: results of the first clinical trial.

OBJECTIVE: To evaluate reproductive, obstetric, and long-term health of the first completed study of uterus transplantation (UTx). DESIGN: Prospective. SETTING: University hospital. PATIENT(S): Nine live donor UTx procedures were conducted and seven were successful. Donors, recipients, and children born were observed. INTERVENTION(S): In vitro fertilization was performed with embryo transfer (ET) of day 2 or day 5 embryos in natural cycles. Pregnancies and growth trajectory of the children born were observed. Health-related quality of life, psychosocial outcome, and medical health of donors and recipients were evaluated by questionnaires. MAIN OUTCOME MEASURE(S): The results of in vitro fertilization, pregnancies, growth of children, and long-term health of patients were reported. RESULT(S): Six women delivered nine infants, with three women giving birth twice (cumulative birth rates of 86% and 67% in surgically successful and performed transplants, respectively). The overall clinical pregnancy rate (CPR) and live birth rate (LBR) per ET were 32.6% and 19.6%, respectively. For day 2 embryos, the CPR and LBR per ET were 12.5% and 8.6%, respectively. For day 5 embryos, the CPR and LBR per ET were 81.8% and 45.4%, respectively. Fetal growth and blood flow were normal in all pregnancies. Time of delivery (median in full pregnancy weeks + days [ranges]) by cesarean section and weight deviations was 35 + 3 (31 + 6 to 38 + 0) and -1% (-13% to 23%), respectively. Three women developed preeclampsia and four neonates acquired respiratory distress syndrome. All children were healthy and followed a normal growth trajectory. Measures of long-term health in both donors and recipients were noted to be favorable. When UTx resulted in a birth, scores for anxiety, depression, and relationship satisfaction were reassuring for both the donors and recipients. CONCLUSION(S): The results of this first complete UTx trial show that this is an effective infertility treatment, resulting in births of healthy children and associated with only minor psychological and medical long-term effects for donors and recipients. CLINICAL TRIAL REGISTRATION NUMBER: NCT02987023.

Long-term incidence of endometrial cancer after endometrial resection and ablation: A population based Swedish gynecologic cancer group (SweGCG) study.

INTRODUCTION: Minimally invasive methods to reduce menorrhagia were introduced in the 1980s and 1990s. Transcervical endometrial resection (TCRE) and endometrial ablation (EA) are two of the most frequently used methods. As none of them can guarantee a complete removal of the endometrium, there are concerns that the remaining endometrium may develop to endometrial cancer (EC) later in life. The primary aim was to analyze the long-term incidence of EC after TCRE and EA in a nationwide population. The secondary aim was to assess the two treatment modalities separately. MATERIAL AND METHODS: The Swedish National Patient Registry and National Quality Registry for Gynecological Surgery were used for identification of women who had TCRE or EA performed between 1997-2017. The cohort was followed from the first TCRE or EA until hysterectomy, diagnosis of EC, or death. Follow-up data were retrieved from the National Cancer Registry and the National Death Registry. Expected incidence for EC in Swedish women was calculated using Swedish data retrieved from the NORDCAN project after having taken into account differences of age and follow-up time. Cumulative incidence of EC after TCRE and EA, was calculated. A standardized incidence ratio was calculated based on the expected and observed incidence, stratified by age and year of diagnosis. RESULTS: In total, 17 296 women (mean age 45.1 years) underwent TCRE (n = 8626) or EA (n = 8670). Excluded were 3121 who had a hysterectomy for benign causes during follow up. During a median follow-up time of 7.1 years (interquartile range 3.1-13.3 years) the numbers of EC were 25 (0.3%) after TCRE and 2 (0.02%) after EA, respectively. The observed incidence was significantly lower than expected (population-based estimate) after EA but not after TCRE, giving a standardized incidence ratio of 0.13 (95% confidence interval [CI] 0.03-0.53) after EA and 1.27 (95% CI 0.86-1.88) after TCRE. Median times to EC were 3.0 and 8.3 years after TCRE and EA, respectively. CONCLUSIONS: There was a significant reduction of EC after EA, suggesting a protective effect, whereas endometrial resection showed an incidence within the expected rate.

Increased survival in non-endometrioid endometrial cancer after introducing lymphadenectomy and tailoring radiotherapy - A population-based cohort study.

OBJECTIVE: To investigate recurrence and survival in non-endometrioid endometrial cancer in a population-based cohort and evaluate the implementation of the first national guidelines (NGEC) recommending pelvic and paraaortic lymphadenectomy for surgical staging and tailored adjuvant therapy. METHODS: A population-based cohort study that used the Swedish quality registry for gynaecological cancer for the identification of all women with early-stage non-endometrioid endometrial cancer between 2010 and 2017. Five-year overall (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. The Cox proportional hazards regression model was used to evaluate the effect of age, FIGO stage, primary treatment and lymph node dissection on DFS. RESULTS: There were 228 patients included in the study cohort and 67 (29%) patients had a recurrence within five years. In the recurrence cohort, the OS was 13.4% (95%CI:7.3-24.7) compared to 88.5% (95%CI:83.4-93.9) if no recurrence occurred (log-rank p < 0.001). The DFS for the complete cohort was 61.9% (95%CI:55.7-68.7). The OS before implementation of NGEC was 57.3% (95%CI:48.2-68.1) and the DFS was 52.1% (95%CI:43.0-63.1) compared to an OS of 72.0% (95%CI:64.2-80.7; log-rank p = 0.018) and a DFS of 70.1% (95%CI:62.4-78.7; log-rank p = 0.008) after implementing NGEC. Patients received adjuvant radiotherapy in 92.7% before and 42.4% after NGEC implementation (p < 0.001). In the multivariable regression analysis, age, FIGO stage and lymph node dissection were found to be significant prognostic factors, where having a lymph node dissection decreased the risk of recurrence or death with a HR of 0.58 (95%CI:0.33-1.00). CONCLUSION: In this population-based cohort of preoperative early-stage non-endometrioid EC, a significant improvement in survival was seen after NGEC implementation where lymph node staging for tailoring adjuvant therapy was introduced and less pelvic radiotherapy was given.

Complications after advanced ovarian cancer surgery-A population-based cohort study.

INTRODUCTION: Surgical complications after primary or interval debulking surgery in advanced ovarian cancer were investigated and associations with patient characteristics and surgical outcomes were explored. MATERIAL AND METHODS: A population-based cohort study including all women with ovarian cancer, FIGO III-IV, treated with primary or interval debulking surgery, 2013-2017. Patient characteristics, surgical outcomes and complications according to the Clavien-Dindo (CD) classification system ≤30 days postoperatively, were registered. Uni- and multivariable regression analyses were performed with severe complications (CD ≥ III) as endpoint. PFS in relation was analyzed using the Kaplan-Meier method. RESULTS: The cohort included 384 women, where 304 (79%) were treated with primary and 80 (21%) with interval debulking surgery. Complications CD I-V were registered in 112 (29%) patients and CD ≥ III in 42 (11%). Preoperative albumin was significantly lower in the CD ≥ III cohort compared with CD 0-II (P = 0.018). For every increase per unit in albumin, the risk of complications decreased by a factor of 0.93. There was no significant difference in completed chemotherapy between the cohorts CD 0-II 90.1% and CD ≥ III 83.3% (P = 0.236). In the univariable analysis; albumin <30 g/L, primary debulking surgery, complete cytoreduction and intermediate/high surgical complexity score (SCS) were associated with CD ≥ III. In the following multivariable analysis, only intermediate/high SCS was found to be an independent significant prognostic factor. Low (n = 180) vs intermediate/high SCS (n = 204) showed a median PFS of 17.2 months (95% confidence interval [CI] 15.2-20.7) vs 21.5 months (95% CI 18.2-25.7), respectively, with a significant log-rank; P = 0.038. CONCLUSIONS: Advanced ovarian cancer surgery is associated with complications but no significant difference was seen in completion of adjuvant chemotherapy when severe complications occur. Importantly, our study shows that intermediate/high SCS is an independent prognostic risk factor for complications. Low albumin, residual disease and primary debulking surgery were found to be associated with severe complications. These results may facilitate forming algorithms in the decision-making procedure of surgical treatment protocols.

Complications and risk factors in vulvar cancer surgery - A population-based study.

INTRODUCTION: Primary surgery for vulvar cancer has become less radical in past decades. This study investigates risk factors and prevalence of short-and long-term complications after up-to-date vulvar cancer surgery. METHODS: Population-based cohort study of surgically treated primary vulvar cancer at a national center of vulvar cancer, assessing surgical outcome. The Swedish Quality Registry for Gynecological Cancer was used for identification, journals reviewed and surgical outcome including complications within 30 days and one year registered. Multivariable logistic regression analysis comprising risk factors of short-term complications; age>80 years, BMI, smoking, diabetes, lichen sclerosus and FIGO stage was performed. RESULTS: 182 patients were identified, whereas 55 had vulvar surgery only, 53 surgery including sentinel lymph node biopsy (SLNB) and 72 surgery including inguinofemoral lymphadenectomy (IFL), with short-term complication rates of 21.8%, 39.6% and 54.2% respectively. Vulvar wound dehiscence was reported in 6.0% and infection in 13.7%. Complication rates were lower after SLNB than IFL (wound dehiscence 0% vs 8.3%; p = 0.04, infection 15.1% vs 36.1%; p = 0.01 and lymphocele 5.7% vs 9.7%; p = 0.52). Severe complications were rare. Persisting lymphedema evolved in 3.8% after SLNB and in 38.6% after IFL (p = 0.001), ubiquitous after adjuvant radiotherapy. In multivariable regression analysis, no associations between included risk factors and complications were found. CONCLUSION: Surgical complications are still common in vulvar cancer surgery and increase with the extent of groin surgery. To thrive for early diagnosis and to avoid IFL seem to be the most important factors in minimizing short-and long-term complications.

The wait time to primary surgery in endometrial cancer - impact on survival and predictive factors: a population-based SweGCG study.

BACKGROUND: Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time. MATERIAL AND METHODS: In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time > 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR). RESULTS: Out of 7366 women, 5535 waited > 32 d for surgery and 1098 > 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time > 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08-1.66) followed by country of birth (OR 1.31, 95% CI 1.10-1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time < 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36-3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival. CONCLUSIONS: Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis.HighlightsSurgery within the first two weeks after diagnosis of endometrial cancer (EC) was associated with poorer survival.A prolonged wait time to surgery did not worsen prognosis.Delay in time to surgery was associated with sociodemographic factors.

Imaging evaluation of uterine arteries in potential living donors for uterus transplantation: a comparative study of MRA, CTA, and DSA.

OBJECTIVE: To evaluate uterine arteries (UA) of potential living donors for uterus transplantation (UTx) by comparison of CT angiography (CTA), digital subtraction angiography (DSA), and MR angiography (MRA) with care taken to minimize radiation doses. METHODS: Prospective donors for a clinical UTx trial were included. CTA, DSA, and MRA measurements in three predefined segments of the UAs were evaluated. Radiation doses were estimated and 1-year graft survival was recorded. RESULTS: Twelve potential donors (age 37-62 years) were investigated. There was no difference in visualized average UA lumen diameter when comparing CTA (mean 2.0 mm, SD 0.4), DSA (mean 2.1 mm, SD 0.6), and MRA (mean 2.0 mm, SD 0.3). MRA was not able to fully evaluate 10 (43%) out of 23 UA that proved to be patent on DSA. One UA was not identified by any of the modalities, and three MRA-absent UAs were identified by both CTA and DSA. The estimated mean effective dose was lower for DSA (5.1 mSv, SD 2.8) than CTA (7.1 mSv, SD 2.0), but not significantly (p value = 0.06). Three potential donors were excluded due to UA pathology and one due to adenomyosis. Eight donors underwent hysterectomy, with 1-year graft survival in six women. CONCLUSION: MRI including MRA should be the initial modality to examine potential UTx donors to acquire valuable details of uterine anatomy, and if UAs are fully visualized, there is no need for further angiographic methods with radiation. If UAs are not visualized by MRA, CTA may be performed and in selective cases with addition of the invasive modality DSA. KEY POINTS: • For uterine transplantation, pelvic MRI with MRA provides information of the uterine structure and of the diameters of uterine arteries in living donors. • Failure of MRA to demonstrate uterine arteries could be followed by CTA which will visualize the uterine arteries in a majority of cases. If MRA and additional CTA provide inconclusive results, the uterine arteries should be further evaluated by DSA. • Information of CTA can be used in the angio-system for DSA settings to minimize the radiation and contrast media doses.

Hysterectomy after uterus transplantation and detailed analyses of graft failures.

INTRODUCTION: The first live birth after uterus transplantation occurred in Sweden in 2014. Uterus transplantation has repeatedly, and at many centers worldwide, proven to be a feasible treatment for absolute uterine factor infertility. Hysterectomy in live donors and transplantation are well described in numerous reports. However, there are no reports of hysterectomy in the recipient after uterus transplantation, which will occur at either graft failure, after childbirth, or after numerous failed pregnancy attempts. We present the first report of hysterectomy in recipients after uterus transplantation with detailed analyses of findings in conjunction with graft failures. MATERIAL AND METHODS: An analysis of recipient hysterectomies (n = 10), performed in 2012-2020, was conducted. Data from the international uterus transplantation registry (ISUTx registry) were extracted, and medical records were systematically reviewed, to collect and compile characteristics of recipients and donors, as well as pre-, per-, and postoperative data, including clinical course of graft failures. RESULTS: Hysterectomy in recipients was performed in conjunction with cesarean section (n = 3), 3-6 months after cesarean section (n = 3), or after failed pregnancy attempts (n = 1) or graft failure (n = 3). The durations of anesthesia (2 h 36 min to 7 h 35 min) and hysterectomy surgery (1 h 42 min to 5 h 52 min) ranged widely, with long perioperative interruptions for insertion of ureteral catheters in two cases. Adhesions to the uterus were abundant, the majority being mild. Three uteri that subsequently showed graft failure (hysterectomy at 1, 3, and 8 months post transplantation) showed histological signs of ischemia in biopsies taken 1-week post-transplant and early signs of central hypoperfusion by Doppler ultrasound. In these graft failure explants, there were no epithelial linings in the uterine cavity or in the cervix. The inner uterine wall was severely ischemic and/or necrotic, whereas outer parts were partly viable. There were signs of moderate atherosclerosis of uterine arteries but no rejection. Mild postoperative complications were frequent (6/10), with one supravaginal hematoma requiring surgical drainage. CONCLUSIONS: Hysterectomy after uterus transplantation is a complex and time-consuming procedure, and perioperative ureteral catheters may be helpful. Histopathology of early cervical biopsies showing ischemic signs may indicate subsequent irreversible damage, leading to graft failure.

Striving for motherhood after uterus transplantation: a qualitative study concerning pregnancy attempts, and the first years of parenthood after transplantation.

STUDY QUESTION: How do women experience attempts to become pregnant, and the first years of motherhood, after uterus transplantation (UTx)? SUMMARY ANSWER: Women who try to become pregnant after UTx experience the general strains typically associated with infertility and childlessness, such as failure of embryo transfer (ET), and specific worries about graft survival but when they become mothers they essentially feel like other mothers, with the associated rewards and stresses. WHAT IS KNOWN ALREADY: UTx has proven to be a successful treatment for absolute uterine factor infertility (AUFI). Although UTx seems to have a positive effect on self-image there is a lack of knowledge about how women who have received uterine grafts experience pregnancy attempts, pregnancy itself and the first years of motherhood. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included the seven participants in the first UTx trial who had experienced surgically successful grafts. Pregnancy was attempted using ET 12 months after transplantation. Structured interviews were performed once a year for 5 years after transplantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Six of the seven participants (mean age 29.3 years at UTx) had AUFI owing to the congenital absence of the uterus, while the seventh woman had undergone a hysterectomy. Post-transplantation, yearly interviews (2013-2018) were performed, comprising a total of 34 interviews. Interview data were analysed thematically. MAIN RESULTS AND THE ROLE OF CHANCE: All seven participants achieved pregnancy during the study period and six became mothers. Experiencing the previously unimaginable was classed as an overarching theme with the following underlying themes: The yoke of childlessness; Going through the impossible and Motherhood as surreal and normal. The results showed that the women who try to achieve motherhood after UTx generally describe their situation as manageable and present strains comparable to other women undergoing infertility treatments. LIMITATIONS, REASONS FOR CAUTION: The fact that all participants came from one centre is a limitation. WIDER IMPLICATIONS OF THE FINDINGS: There are real psychological strains in motherhood after UTx, such as the concern the women expressed relating to health of the child and the effects of immunosuppressants. These findings are in line with those of other women who became pregnant after transplantation of organs other than the uterus. The results show that extra psychological support and attention should be given to those with repeated pregnancy failures or unsuccessful outcomes. In the cases where women became mothers, attention needs to be given to the possible worries connected to the UTx, but in other respects, they should be treated like any mother-to-be. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from the Jane and Dan Olsson Foundation for Science; Knut and Alice Wallenberg Foundation. A.L.F. grant from the Swedish state under an agreement between the government and the county councils; Swedish Research Council. The authors have no competing interests. TRIAL REGISTRATION NUMBER: NCT01844362.