Risk factors for lymph node metastases in women with endometrial cancer : A population-based, nation-wide register study—On behalf of the Swedish Gynecological Cancer Group

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010–2015 with FIGO Stages I–III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI ≥ 50% (risk ratio [RR] = 4.1; 95% confidence interval [CI] 3.0–5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4–2.4) and FIGO Grade 3 compared to Grade 1–2 tumors (RR 1.5; CI 1.1–2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI ≥ 50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not

Preclinical report on allogeneic uterus transplantation in non-human primates

STUDY QUESTION Is it possible to perform allogeneic uterus transplantation (UTx) with a donation from a live donor in a non-human primate species and what immunosuppression is needed to prevent rejection? SUMMARY ANSWER Allogeneic UTx in the baboon is a donor- and recipient-safe surgical procedure; immunosuppression with induction therapy and a triple protocol should be used. WHAT IS KNOWN ALREADY UTx may become a treatment for absolute uterine factor infertility. Autologous UTx models have been developed in non-human primates with reports on long-term survival of the uterine grafts. STUDY DESIGN, SIZE AND DURATION This experimental study included 18 female baboons as uterus donors and 18 female baboons as uterus recipients. The follow-up time was 5–8 weeks. PARTICIPANTS/MATERIALS, SETTING AND METHODS Uterus retrieval was performed with extended hysterectomy including bilateral uterine and internal iliac arteries and ovarian veins. After UTx, with vascular anastomoses unilateral to the internal iliac artery and the external iliac vein, the uterus recipients received one of the following: no immunosuppression (n = 4); monotherapy (oral slow release tacrolimus) (n = 4) or induction therapy (antithymocyte globulin) followed by triple therapy (tacrolimus, mycophenolate, corticosteroids; n = 10). Surgical parameters, survival, immunosuppression and rejection patterns were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE The durations of uterus retrieval and recipient surgery were around 3 and 3.5 h, respectively. The total ischemic time was around 3 h. All the recipients and the donors survived the surgery. All the recipients presented rejection to some extent within the first weeks following UTx. In one recipient, the uterus was of normal appearance at the end of the study period. In spite of occasional high (>60 ng/ml) blood levels of tacrolimus, there was no evidence of nephrotoxicity. LIMITATIONS AND REASONS FOR CAUTION This initial non-human primate allogeneic UTx study indicates that further research is needed to optimize immunosuppression protocols in order to avoid uterine rejection. WIDER IMPLICATIONS OF THE FINDINGS The findings suggest that allogeneic UTx in primate species is feasible but continued work on this issue is needed. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Swedish Research Council, ALF University of Gothenburg, Hjalmar Svensson Foundation and by Jane and Dan Olsson Research Foundation. The authors do not have any competing interest

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