1. |
- Karlsson, Anna, et al.
(author)
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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
- 2024
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In: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 581-585
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Journal article (peer-reviewed)abstract
- 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.
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2. |
- Karlsson, Anna, 1985-, et al.
(author)
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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
- 2024
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In: Acta Oncologica. - Uppsala : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 581-585
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Journal article (peer-reviewed)abstract
- 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.
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3. |
- Akouri, Randa R., et al.
(author)
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First live birth after uterus transplantation in the Middle East
- 2020
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In: Middle East Fertility Society Journal. - : Springer Science and Business Media LLC. - 1110-5690 .- 2090-3251. ; 25:1
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Journal article (peer-reviewed)abstract
- Background The first live birth after uterus transplantation took place in Sweden in 2014. It was the first ever cure for absolute uterine factor infertility. We report the surgery, assisted reproduction, and pregnancy behind the first live birth after uterus transplantation in the Middle East, North Africa, and Turkey (MENAT) region. A 24-year old woman with congenital absence of the uterus underwent transplantation of the uterus donated by her 50-year-old multiparous mother. In vitro fertilization was performed to cryopreserve embryos. Both graft retrieval and transplantation were performed by laparotomy. Donor surgery included isolation of the uterus, together with major uterine arteries and veins on segments of the internal iliac vessels bilaterally, the round ligaments, and the sacrouterine ligaments, as well as with bladder peritoneum. Recipient surgery included preparation of the vaginal vault, end-to-side anastomosis to the external iliac arteries and veins on each side, and then fixation of the uterus. Results One in vitro fertilization cycle prior to transplantation resulted in 11 cryopreserved embryos. Surgical time of the donor was 608 min, and blood loss was 900 mL. Cold ischemia time was 85 min. Recipient surgical time was 363 min, and blood loss was 700 mL. Anastomosis time was 105 min. Hospital stay was 7 days for both patients. Ten months after the transplantation, one previously cryopreserved blastocyst was transferred which resulted in viable pregnancy, which proceeded normally (except for one episode of minor vaginal bleeding in the 1st trimester) until cesarean section at 35 + 1 weeks due to premature contractions and shortened cervix. A healthy girl (Apgar 9-10-10) weighing 2620 g was born in January 2020, and her development has been normal during the first 6 months. Conclusions This is the first report of a healthy live birth after uterus transplantation in the MENAT region. We hope that this will motivate further progress and additional clinical trials in this area in the Middle East Region, where the first uterus transplantation attempt ever, however unsuccessful, was performed already three decades ago.
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4. |
- Ayoubi, Jean Marc, et al.
(author)
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Case Report: Post-Partum SARS-CoV-2 Infection After the First French Uterus Transplantation
- 2022
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In: Frontiers in Surgery. - : Frontiers Media SA. - 2296-875X. ; 9
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Journal article (peer-reviewed)abstract
- 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.
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5. |
- Ayoubi, J. M., et al.
(author)
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Evolving clinical challenges in uterus transplantation
- 2022
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In: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483. ; 45:5, s. 947-960
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Research review (peer-reviewed)abstract
- 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.
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6. |
- Borgfeldt, Christer, et al.
(author)
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Survival in endometrial cancer in relation to minimally invasive surgery or open surgery : a Swedish Gynecologic Cancer Group (SweGCG) study
- 2021
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In: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 21:1
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Journal article (peer-reviewed)abstract
- BackgroundThe 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).MethodsA 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.ResultsIn 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.ConclusionThe 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.
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7. |
- Broecker, Verena, et al.
(author)
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Uterus transplantation: Histological findings in explants at elective hysterectomy
- 2021
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 21:2, s. 798-808
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Journal article (peer-reviewed)abstract
- 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.
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8. |
- Brucker, S. Y., et al.
(author)
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Living-Donor Uterus Transplantation: Pre-, Intra-, and Postoperative Parameters Relevant to Surgical Success, Pregnancy, and Obstetrics with Live Births
- 2020
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In: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 9:8
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Journal article (peer-reviewed)abstract
- Uterus transplantation (UTx) can provide a route to motherhood for women with Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS), a congenital disorder characterized by uterovaginal aplasia, but with functional ovaries. Based on our four successful living-donor transplantations and two resulting births, this analysis presents parameters relevant to standardizing recipient/donor selection, UTx surgery, and postoperative treatment, and their implementation in routine settings. We descriptively analyzed prospectively collected observational data from our four uterus recipients, all with MRKHS, their living donors, and the two newborns born to two recipients, including 1-year postnatal follow-ups. Analysis included only living-donor/recipient pairs with completed donor/recipient surgery. Two recipients, both requiring ovarian restimulation under immunosuppression after missed pregnancy loss in one case and no pregnancy in the other, each delivered a healthy boy by cesarean section. We conclude that parameters crucial to successful transplantation, pregnancy, and childbirth include careful selection of donor/recipient pairs, donor organ quality, meticulous surgical technique, a multidisciplinary team approach, and comprehensive follow-up. Surgery duration and blood vessel selection await further optimization, as do the choice and duration of immunosuppression, which are crucial to timing the first embryo transfer. Data need to be collected in an international registry due to the low prevalence of MRKHS.
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9. |
- Brännström, Mats, 1958, et al.
(author)
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Evolution of surgical steps in robotics-assisted donor surgery for uterus transplantation: results of the eight cases in the Swedish trial.
- 2020
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In: Fertility and sterility. - : Elsevier BV. - 1556-5653 .- 0015-0282. ; 114:5, s. 1097-1107
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Journal article (peer-reviewed)abstract
- To perform a stepwise development of the surgical method for robotics-assisted laparoscopy in donor hysterectomy for uterus transplantation (UTx), a unique treatment for absolute uterine-factor infertility.Prospective observational study.University hospital.Eight donors, aged 38-62 years, underwent surgery for retrieval of the uterus and vasculature.Robotics-assisted laparoscopy was performed in donors for 6-7 h with video recording. Conversion to laparotomy was performed for last parts of retrieval surgery.Description, evaluation, and timing of 12 specific surgical steps, as well as surgical outcomes and complications.There was a progression during the course of eight surgeries. In the initial two cases, seven and six items were completed with robotics compared with all 12 items in the last three procedures. The passive surgical time decreased from ∼20% in the first four cases to ∼8% in the last three procedures. The estimated median (range) blood loss, total surgical time, and length of hospital stay were, respectively, 125 mL (100-600), 11.25 h (10-13), and 5.5 days (5-6). Two reversible complications occurred: One patient acquired pressure alopecia, and one developed pyelonephritis.The study demonstrates a clear evolution of a strategy toward fully robotic donor surgery in UTx. This is likely to become the main approach in donor surgery of live UTx donors.NCT02987023.
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10. |
- Brännström, Mats, 1958, et al.
(author)
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Fixation of the uterine graft after uterus transplantation
- 2020
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In: Uterus Transplantation. Brännström M. (red.). - Cham : Springer. - 9783319941622 ; , s. 147-149
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Book chapter (other academic/artistic)abstract
- At uterus transplantation into the recipient, surgical fixation of the uterus is important and performed after anastomoses of the vasculature and the vagina which has been done in order to minimize warm ischemia and secure optimal location of the uterus with its vessels. At the stage of fixation, the uterine graft is reperfused. The fixation of the uterus is recommended onto several ligamentous structures in order to prevent prolapse of the organ in the pregnant and non-pregnant state. © Springer Nature Switzerland AG 2020.
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