The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy - the TABANETOC trial: study protocol for a randomized clinical multicenter trial.

BACKGROUND: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis. PURPOSE: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT. MATERIAL AND METHODS: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured. PATIENTS: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0-1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants. INTERPRETATION: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.

Health-related quality of life, sexual function, psychological health, reproductive concerns and fertility outcome in young women treated with fertility-sparing surgery for ovarian tumors - A prospective longitudinal multicentre study.

OBJECTIVE: This study aimed to investigate health-related quality of life (HRQoL), sexual function, psychological-health, reproductive concerns, and fertility outcomes of women of reproductive age undergoing Fertility-Sparing Surgery (FSS) for treatment of ovarian cancer (OC) or borderline ovarian tumor (BOT), over a 2-year period. METHODS: Prospective longitudinal multicentre study including women 18-40 years undergoing FSS between 2016 and 2018 in Sweden. Clinical data at diagnosis, histopathological findings and 2-year follow-up regarding oncological and reproductive outcomes were collected. Participants completed the EORTC QLQ-C30 and OV-28, FSFI, HADS and study-specific items at time of diagnosis and at one- and two-years following FSS. Data were analysed using a model for repeated measures to investigate changes over time. RESULTS: Of 68 eligible women, 49 were included following exclusions due to benign pathology or subsequent radical surgery. During a mean follow-up of 20.5 months, two women experienced a recurrence and 82% reported regular menstruations. The majority (94%) had a strong desire to become biological mothers, which remained or increased over time. The conception-rate was 76%. HRQoL, psychological-health and sexual function improved over time and the proportion of women with sexual dysfunction decreased. At one-year follow-up 50% of nulliparous women had scores indicating sexual dysfunction compared to 0% of the women who had given birth either before or after surgery (p = 0.008). CONCLUSION: HRQoL, psychological-health and sexual function improved during two-year follow-up after FSS in young women presenting with OC or BOT. Women who had given birth prior to or after FSS reported improved sexual function compared to nulliparous women.

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.

Trasplante uterino: resultados actuales. Preparación de un equipo multidisciplinario en Argentina / Uterine transplant: current results. Preparation of a multidisciplinary team in argentina

El factor uterino absoluto como causa de infertilidad, ya sea la ausencia de útero o la presencia de útero no funcional, es actualmente una patología con posibilidad de tratamiento. El primer intento de trasplante uterino en humanos fue en el año 2000, este falló y el útero necrótico tuvo que ser removido luego de 99 días. Este caso pionero inspiró a varios grupos de investigación alrededor del mundo para comenzar estudios en animales para investigar el trasplante uterino en relación a cirugía, inmunosupresión, rechazo y resultados obstétricos. El primer estudio clínico de trasplante uterino comenzó en Suecia en el año 2013 donde se realizaron nueve procedimientos a partir de donantes vivas. El primer nacido vivo en el mundo a partir de un trasplante uterino se reportó en septiembre del año 2014, luego se comunicaron dos nacimientos más en noviembre de ese mismo año. Desde ese momento se han reportado nacimientos de trasplantes uterinos en Suecia, Estados Unidos y Brasil. El caso de nacido vivo en Brasil es el primer y único nacimiento en el mundo cuya donante fue cadavérica. Todos los casos publicados de trasplante uterino y nacidos vivos serán revisados en detalle en este artículo. En el año 2016 se realizó el primer simposio de trasplante uterino en América Latina bajo el auspicio de la Asociación Latinoamericana de Medicina Reproductiva (ALMER). En ese encuentro, el equipo de la Universidad de Gotemburgo, Suecia, compartió su experiencia en trasplante uterino en humanos. Este fue nuestro puntapié para comenzar un trabajo colaborativo entre nuestro equipo en Rosario y el equipo de Suecia, con la intención de preparar un estudio científico de trasplante uterino en Argentina. Los pasos importantes para este procedimiento serán revisados en este artículo (AU)

Absolute uterine factor infertility, due to absence or non-function of the uterus, is now treatable. The first attempt of human uterus transplantation was in year 2000, but it failed and a necrotic uterus had to be removed after 99 days. This pioneering case inspired several research groups around the globe to initiate animal-based studies to investigate uterus transplantation in relation to surgery, immunosuppression, rejection and pregnancy outcome. The first clinical trial of uterus transplantation was initiated in Sweden in 2013 and involved nine live donor procedures. The world ́s first live birth was reported from that trial in September 2014 and this was followed by two more births within the trial in November 2014. Births after uterus transplantation has since then been reported from Sweden, USA and Brazil. The live birth in Brazil is the first and only birth from a deceased donor so far. All published cases of uterus transplantation and the live births will be review in detail.In 2016 there was the first symposium on uterus transplantation in Latin-America under the auspice of ALMER. At the meeting, the Swedish team shared their experiences of human uterus transplantation. This was the starting point for a collaboration work between our team in Rosario and the Swedish team, with the aim to prepare for a scientific trial of uterus transplantation in Argentina. The important steps in this procedure will be reviewed (AU)