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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Risk of epithelial ovarian cancer Type I and II after hysterectomy, salpingectomy and tubal ligation-A nationwide case-control study.

The proposed different origins and pathways to of the dualistic model of epithelial ovarian cancer (EOC) may affect and alter the potential risk reduction related to hysterectomy, salpingectomy and tubal ligation. The aim of our study was to analyze associations between hysterectomy, salpingectomy or tubal ligation and risk reduction of EOC Type I and II. In this nationwide register-based case-control study, women diagnosed with EOC, Fallopian tube or primary peritoneal cancer between 2008 and 2014 were included. Cases were classified into Type I and II according to histology and predefined criteria. The exposure variables: hysterectomy, salpingectomy and tubal ligation were identified from national registries. Conditional logistic regression analyses were performed to evaluate associations between Type I and II EOC and the exposure variables. Among 4669 registered cases, 4040 were eligible and assessed for subtyping resulting in 1033 Type I and 3007 Type II. Ten controls were randomly assigned to each case from the register of population. In regression analyses, women with previous salpingectomy had a significantly lower risk of EOC Type II (odds ratio [OR] 0.62; 95% confidence interval [95%CI] 0.45-0.85) but not Type I (OR 1.16; 95%CI 0.75-1.78). Hysterectomy was associated with a reduced risk of both EOC Type I (OR 0.71; 95%CI 0.52-0.99) and Type II (OR 0.81; 95%CI 0.68-0.96). Similar estimates were obtained for tubal ligation, although without statistical significance. The association between salpingectomy and reduced risk of EOC Type II supports the proposed theory of high-grade serous cancer originating from the tubal fimbriae.

Uterus transplantation: Histological findings in explants at elective hysterectomy.

Uterus transplantation has enabled women with absolute uterine factor infertility to carry a pregnancy. The first human uterus transplantation trial was initiated in 2013 in Gothenburg, Sweden. It was completed with 7 transplantations with long-term allograft survival and 9 children born from 6 women. In the present study we describe the histopathology of these 7 allografts, which were removed at 22-83 months after transplantation, and compare findings to control cases. Morphological findings in a subset of explants included linear subepithelial inflammation and perivascular stromal inflammation in the cervix, small inflammatory foci in the myometrium, and intimal inflammation in larger arteries. The average number of T cells, B cells, and macrophages was higher in transplants compared to normal controls, but variability was high among transplants. Chronic-active vascular rejection was seen in 2 of 7 transplants, both showed also inflammation in the cervix. Further, the inflammation seen in the cervix reflected the inflammation in the myometrium, suggesting that cervical biopsies are suitable to monitor rejection. However, the degree of inflammation and signs of rejection in explants did not reflect on the possibility to become pregnant in this limited series.

Survival in endometrial cancer in relation to minimally invasive surgery or open surgery - a Swedish Gynecologic Cancer Group (SweGCG) study.

BACKGROUND: The aim of this study was to analyze overall survival in endometrial cancer patients' FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy). METHODS: A population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses. RESULTS: In univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18-1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95-1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival. CONCLUSION: The minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.

Implementation of National Guidelines increased survival in advanced ovarian cancer - A population-based nationwide SweGCG study.

AIM: The first Swedish National Guidelines for Ovarian Cancer (NGOC) were published in 2012. We aimed to evaluate surgical outcomes and survival in patients with stage IIIC-IV disease, before and after the NGOC implementation. METHOD: Women with primary epithelial ovarian cancer, FIGO stage IIIC-IV, registered in the Swedish Quality Registry for Gynecologic Cancer 2008-2011 and 2013-2016 were included. Surgical outcomes were analyzed, including frequency of complete cytoreduction (R0). Relative survival (RS) and excess mortality rate ratios (EMRRs) were computed as measures of survival. Univariable and multivariable regression (Poisson) were calculated. RESULTS: In total, 3728 women were identified, 1746 before and 1982 after NGOC. After adjusting for age and stage, survival was improved 2013-2016 vs. 2008-2011 (EMRR 0.89; 95%CI:0.82-0.96, p < 0.05). For women undergoing primary debulking surgery (PDS), R0 frequency (28.9% vs. 53.3%; p < 0.001) and 5-year RS (29.6% (95%CI:26.8-32.8) vs. 37.4% (95%CI:33.6-41.7)) were increased, but fewer patients (58% vs. 44%, p < 0.001) underwent PDS after NGOC implementation. Median survival for the PDS cohort increased from 35 months (95%CI,32.8-39.2) to 43 months (95%CI,40.9-46.4). In the neoadjuvant chemotherapy (NACT) + interval debulking surgery (IDS) cohort, R0 increased (36.8% to 50.1%, p < 0.001), but not 5-year RS (17.5% vs. 20.7%, ns). Compared to PDS, the EMRR was 1.32 (95%CI,1.19-1.47, p < 0.001) for NACT+IDS and 3.00 (95%CI,2.66-3.38, p < 0.001) for chemotherapy alone. In multivariable analyses, PDS, R0, age ≤ 70 years, and stage IIIC were found to be independent factors for improved RS. CONCLUSION: Implementation of the first National Guidelines for Ovarian Cancer improved relative survival in advanced ovarian cancer.

Uterus transplantation for fertility preservation in patients with gynecologic cancer.

Cervical and endometrial cancer may impact women interested in future fertility in approximately 5-25% of cases. The recommended treatment for patients with early stage disease is hysterectomy and/or radiation leading to infertility. This is referred to as absolute uterine factor infertility. Such infertility was considered untreatable until 2014, when the first child was born after uterus transplantation. Thereafter, multiple births have been reported, mainly from women with Mayer-Rokitansky-Küster-Hauser syndrome, with congenital uterine absence, although also from a patient with iatrogenic uterine factor infertility caused by radical hysterectomy secondary to an early stage cervical cancer 7 years before uterus transplantation. A live birth after uterus transplantation may be considered promising for many who may not otherwise have this option.Uterus transplantation is a complex process including careful patient selection in both recipients and donors, in vitro fertilization, and complex surgery in the organ procurement procedure including harvesting the vessel pedicles with the thin-walled veins. Thereafter, the transplantation surgery with anastomosis to ensure optimal blood inflow and outflow of the transplanted organ. Knowledge regarding immunosuppression and pregnancy is essential. Lastly there is the hysterectomy component as the uterus must be removed. Multidisciplinary teams working closely are essential to achieve successful uterus transplantation and, ultimately, delivery of a healthy child. Both the living and deceased donor concept may be considered and we address both the advantages and disadvantages. This review summarizes the animal research thus far published on uterus transplantation, the suggested recipient selections including former gynecologic cancer patients, the living and deceased donor uterus transplantation concepts with reported results, and updated fertility outcomes.

Preoperative and intraoperative assessment of myometrial invasion in endometrial cancer-A Swedish Gynecologic Cancer Group (SweGCG) study.

INTRODUCTION: Deep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice. MATERIAL AND METHODS: This is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I-III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard. RESULTS: In the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively. CONCLUSIONS: In Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI.