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.
What's new?
The dualistic model of epithelial ovarian cancer proposes different tumour origins and pathways, which may be reflected in the potential risk reduction related to hysterectomy, salpingectomy, and tubal ligation. In this nationwide register‐based case control study, salpingectomy had an inverse association with epithelial ovarian cancer Type II but not Type I, supporting the theory of high‐grade serous cancer originating from the fimbriae of the Fallopian tube. These results are valuable in the understanding of the origin of various histological subtypes of epithelial ovarian cancer and strengthen the need for prospective studies to evaluate the clinical net benefit of opportunistic salpingectomy.
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.
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.
Some uterus allografts exhibit findings, including subepithelial linear inflammation in the cervix, inflammatory foci in the myometrium, and intimal inflammation in larger arteries, that are not seen in native uteruses.
Uterus transplantation (UTx) has been successfully introduced as a treatment option for women with absolute uterine factor infertility (AUFI). AUFI representing approximately 3% to 5% of the female ...general population is linked to either congenital uterine agenesis (Mayer-Rokitansky-Küster-Hauser syndrome), major congenital uterine malformation (hypoplastic uterus, fraction of bicornuate/unicornuate uterus), a surgically absent uterus, or an acquired condition (intrauterine adhesions, leiomyoma) linked to uterine malfunction that causes implantation failure or defect placentation. The world's first clinical uterus transplant was performed in 2000. However, a hysterectomy became necessary shortly after the surgery due to uterine necrosis. In 2011, a group in Turkey reported on a surgically successful deceased donor transplant; however, this procedure has, to date, not resulted in a healthy live birth, the ultimate goal of UTx. Building on an extensive experimental background in various animal models, including primates, the Gothenburg group led by Brännström reported on the first delivery of a healthy baby in a recipient of a live donor UTx in 2014. This event did not only show the feasibility of UTx, it also helped defining relevant areas of clinical and basic research. Use of a gestational surrogate carrier, is, at least in theory, an alternative for a woman with AUFI seeking genetic motherhood. However, in the clear majority of countries worldwide, gestational surrogacy is not practiced based on legal, ethical, or religious concerns. Of note, the overwhelming majority of surveyed women in the United Kingdom, a country which permits surrogacy, preferred UTx over gestational surrogacy and adoption. Moreover, randomly selected women of fertile age in Sweden preferred UTx over gestational surrogacy. A recent large survey in Japan with more than 3000 participants revealed that UTx had a twofold higher acceptance rate compared with gestational surrogacy. In a recent US survey exploring the potential of donating vascularized composite allografts, uterus donation achieved the highest priority. Thus, the acceptance of UTx as infertility treatment for women with AUFI is high, although the procedure remains in its infancy. Here, we provide an update of clinical activities, summarize achievements and challenges, and submit areas of research interests.
Livebirth after uterus transplantation Brännström, Mats, Prof; Johannesson, Liza, MD; Bokström, Hans, MD ...
The Lancet,
02/2015, Letnik:
385, Številka:
9968
Journal Article
Recenzirano
Odprti dostop
Summary Background Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. ...Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported. Methods In 2013, a 35-year-old woman with congenital absence of the uterus (Rokitansky syndrome) underwent transplantation of the uterus in Sahlgrenska University Hospital, Gothenburg, Sweden. The uterus was donated from a living, 61-year-old, two-parous woman. In-vitro fertilisation treatment of the recipient and her partner had been done before transplantation, from which 11 embryos were cryopreserved. Findings The recipient and the donor had essentially uneventful postoperative recoveries. The recipient's first menstruation occurred 43 days after transplantation and she continued to menstruate at regular intervals of between 26 and 36 days (median 32 days). 1 year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy. She was then given triple immunosuppression (tacrolimus, azathioprine, and corticosteroids), which was continued throughout pregnancy. She had three episodes of mild rejection, one of which occurred during pregnancy. These episodes were all reversed by corticosteroid treatment. Fetal growth parameters and blood flows of the uterine arteries and umbilical cord were normal throughout pregnancy. The patient was admitted with pre-eclampsia at 31 full weeks and 5 days, and 16 h later a caesarean section was done because of abnormal cardiotocography. A male baby with a normal birthweight for gestational age (1775 g) and with APGAR scores 9, 9, 10 was born. Interpretation We describe the first livebirth after uterus transplantation. This report is a proof-of-concept for uterus transplantation as a treatment for uterine factor infertility. Furthermore, the results show the feasibility of live uterus donation, even from a postmenopausal donor. Funding Jane and Dan Olsson Foundation for Science.
Introduction
The proof‐of‐concept of uterus transplantation, as a treatment for absolute uterine factor infertility, came with the first live birth after uterus transplantation, which took place in ...Sweden in 2014. This was after a live donor procedure, with laparotomy in both donor and recipient. In our second, ongoing trial we introduced a robotic‐assisted laparoscopic surgery of the donor to develop minimal invasive surgery for this procedure. Here, we report the surgery and pregnancy behind the first live birth from that trial.
Material and methods
In the present study, within a prospective observational study, a 62‐year‐old mother was the uterus donor and her 33‐year‐old daughter with uterine absence as part of the Mayer‐Rokitansky‐Küster‐Hauser syndrome, was the recipient. Donor surgery was mainly done by robotic‐assisted laparoscopy, involving dissections of the utero‐vaginal fossa, arteries and ureters. The last part of surgery was by laparotomy. Recipient laparotomy included vascular anastomoses to the external iliac vessels. Data relating to in vitro fertilization, surgery, follow up, obstetrics and postnatal growth are presented.
Results
Three in vitro fertilization cycles prior to transplantation gave 12 cryopreserved embryos. The surgical time of the donor in the robot was 360 minutes, according to protocol. The durations for robotic surgery for dissections of the utero‐vaginal fossa, arteries and ureters were 30, 160 and 84 minutes, respectively. The remainder of donor surgery was by laparotomy. Recipient surgery included preparations of the vaginal vault, three end‐to‐side anastomoses (one arterial, two venous) on each side to the external iliacs and fixation of the uterus. Ten months after transplantation, one blastocyst was transferred and resulted in pregnancy, which proceeded uneventfully until elective cesarean section in week 36+1. A healthy boy (Apgar 9‐10‐10) was delivered. Follow up of child has been uneventful for 12 months.
Conclusions
This is the first report of a live birth after use of robotic‐assisted laparoscopy in uterus transplantation and is thereby a proof‐of‐concept of use of minimal invasive surgery in this new type of transplantation.
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.
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.
Absolute uterine factor infertility, due to absence or non-function of the uterus, is one of the few major subgroups of infertility that has remained without any treatment. Uterus transplantation has ...now been proposed as treatment for this type of infertility. The first attempt of human uterus transplantation was in 2000. This was a live donor case, but due to suboptimal surgical solutions it resulted in a necrotic uterus being removed after 99 days. This first human case, although a failure, 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 research was carried out in several animal species and advanced the field substantially. In 2011, the second uterus transplantation attempt was performed, and this involved a deceased donor procedure. Although the case was surgically successful, with resumed menstruations, clinical pregnancy with live birth could not be achieved. 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 that trial in November 2014. Births after uterus transplantation has since been reported from Sweden and other centers in Europe, North America, Latin America, and Asia. Thirty human uterus transplantation procedures have been reported in the scientific literature so far but by our personal knowledge the double number of procedures have been performed. The published cases will be reviewed in detail, and we will also describe the pregnancies of the live births that have been published. A small number of graft failures have occurred. These may in part be linked to suboptimal selection of donors, specifically concerning the quality of the uterine arteries. Consequently, we will also address the issue of strategies for pre-surgical screening of donors.
To report the 12-month outcome of seven patients with viable uteri after uterus transplantation (UTx).
Prospective observational study.
University hospital.
Seven patients with absolute uterine ...infertility and viable uteri for 12 months after live-donor UTx.
Predetermined immunosuppression was with tacrolimus and mychophenolate mofetil (MMF) during 6 months, whereupon MMF should be withdrawn. Frequent ultrasound examinations were performed to assess uterine appearance and uterine artery blood flow. Cervical biopsies (for histological detection of rejection) were obtained at preset time points, with temporary adjustments of immunosuppression if there were signs of rejection. Menstruations were systematically recorded.
Menstruation, uterine artery blood flow, histology of cervical biopsies, and blood levels of tacrolimus.
All patients showed regular menses after 1-2 months. Uterine artery blood flow was unchanged, with a median pulsatility index of 1.9 (range, 0.5-5.4). Blood levels of tacrolimus were approximately 10, 9, and 8 (μg/L) during months 2, 9, and 12, respectively. Four recipients showed mild inflammation in biopsies after MMF withdrawal and were treated with corticosteroids and azathioprine during the remainder of the 12 months. Subclinical rejection episodes were detected on ectocervical biopsies in five recipients. Histology showed apoptotic bodies and occasional spongiosis in the squamous epithelium. Moderate infiltration of lymphocytes and neutrophils was seen in the epithelial/stromal interface. All rejection episodes were successfully treated for 2 weeks with corticosteroids or dose increments of tacrolimus.
We demonstrate long-term uterine viability after UTx, with continued menstruation and unaltered uterine artery blood flow. Subclinical rejection episodes were effectively reversed by temporary increase of immunosuppression.
NCT01844362.
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