| 1. |
- Abeling, T., et al.
(författare)
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Risk factors for death in kidney transplant patients: analysis from a large protocol biopsy registry
- 2019
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 34:7, s. 1171-1181
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Identification and quantification of the relevant factors for death can improve patients' individual risk assessment and decision-making. We used a well-documented patient cohort (n=892) in a renal transplant programme with protocol biopsies to establish multivariable Cox models for risk assessment at 3 and 12months post-transplantation. METHODS: Patients transplanted between 2000 and 2007 were observed up to 11years (total observation 5227 patient-years; median 5.9years). Loss to follow-up was negligible (n=15). A total of 2251 protocol biopsies and 1214 biopsies for cause were performed. All rejections and clinical borderline rejections in protocol biopsies were treated. RESULTS: Overall 10-year patient survival was 78%, with inferior survival of patients with graft loss and superior survival of patients with living-donor transplantation. Eight factors were common in the models at 3 and 12months, including age, pre-transplant heart failure and a score of cardiovascular disease and type 2 diabetes, post-transplant urinary tract infection, treatment of rejection, new-onset heart failure, coronary events and malignancies. Additional variables of the model at 3months included deceased donor transplantation, transplant lymphocele, BK virus nephropathy and severe infections. Graft function and graft loss were significant factors of the model at 12months. Internal validation and validation with a separate cohort of patients (n=349) demonstrated good discrimination of the models. CONCLUSIONS: The identified factors indicate the important areas that need special attention in the pre- and post-transplant care of renal transplant patients. On the basis of these models, we provide nomograms as a tool to weigh individual risks that may contribute to decreased survival. © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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| 2. |
- Broecker, Verena, et al.
(författare)
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Reproducibility of Rejection Grading in Uterus Transplantation: A Multicenter Study.
- 2023
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Ingår i: Transplantation Direct. - 0041-1337 .- 1534-6080. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Diagnosis of rejection after uterus transplantation is based on histopathological examination of ectocervical biopsies. Inflammation at the stromal-epithelial interface is the backbone of the histopathological classification proposed by our group in 2017. However, the reproducibility of this grading scheme has not been tested, and it is unclear whether it covers the full morphological spectrum of rejection.We present a multicenter study in which 5 pathologists from 4 uterus transplantation centers performed 2 rounds of grading on 145 and 48 cervical biopsies, respectively. Three of the centers provided biopsies. Additionally, the presence of perivascular stromal inflammation was recorded. During discussions after the first round, further histological lesions (venous endothelial inflammation and apoptosis) were identified for closer evaluation and added to the panel of lesions to score in the second round. All participants completed a questionnaire to explore current practices in handling and reporting uterus transplant biopsies.Cervical biopsies were commonly performed in all centers to monitor rejection. Intraobserver reproducibility of rejection grading (performed by 1 rater) was excellent, whereas interobserver reproducibility was moderate and did not improve in the second round. Reproducibility of perivascular stromal inflammation was moderate but unsatisfactory for venous endothelial inflammation and apoptosis. All lesions were more frequent in, but not restricted to, biopsies with rejection patterns.Grading of rejection in cervical biopsies is reproducible and applicable to biopsies from different centers. Diagnosis of rejection may be improved by adding further histological lesions to the grading system; however, lesions require rigorous consensus definition.
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| 3. |
- Broecker, Verena, et al.
(författare)
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Uterus transplantation: Histological findings in explants at elective hysterectomy
- 2021
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 21:2, s. 798-808
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Brännström, Mats, 1958, et al.
(författare)
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Outcome of Recipient Surgery and 6-Month Follow-Up of the Swedish Live Donor Robotic Uterus Transplantation Trial.
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Uterus transplantation has proved to be a feasible treatment for uterine factor infertility. Herein, we report on recipient outcome in the robotic uterus transplantation trial of 2017-2019. The eight recipients had congenital uterine aplasia. The donors were six mothers, one sister, and one family friend. Donor surgery was by robotic-assisted laparoscopy. Recipient surgery was by laparotomy and vascular anastomoses to the external iliacs. The duration (median (ranges)) of recipient surgery, blood loss, measured (left/right) uterine artery blood flow after reperfusion, and length of hospital stay were 5.15 h (4.5-6.6), 300 mL (150-600), 43.5 mL/min (20-125)/37.5 mL/min (10-98), and 6 days (5-9), respectively. Postoperative uterine perfusion evaluated by color Doppler showed open anastomoses but restricted blood distribution in two cases. Repeated cervical biopsies in these two cases initially showed ischemia and, later, necrosis. Endometrial growth was not seen, and hysterectomy was later performed, with pathology showing partly viable myometrium and fibrosis but necrosis towards the cavity. The other six patients acquired regular menstrual cyclicity. Surgery was performed in two patients to correct vaginal stenosis. Reversible rejection episodes were seen in two patients. In conclusion, the rate of viable uterine grafts during the initial 6-months of the present study (75%) leaves room for improvement in the inclusion/exclusion criteria of donors and in surgical techniques. Initial low blood flow may indicate subsequent graft failure.
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| 5. |
- Karlsson, Camilla, 1977, et al.
(författare)
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Hysterectomy after uterus transplantation and detailed analyses of graft failures
- 2022
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Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 101:3, s. 355-363
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Mölne, Johan, 1958, et al.
(författare)
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Monitoring of human uterus transplantation with cervical biopsies - a provisional scoring system for rejection.
- 2017
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Ingår i: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. - : Elsevier BV. - 1600-6143. ; 17:6, s. 1628-1636
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Tidskriftsartikel (refereegranskat)abstract
- Until now, absolute uterine factor infertility has been the major untreatable form of female infertility. Recently, uterus transplantation has proven to be the first successful treatment for absolute uterine factor infertility, with demonstration of live births. Here, live donation uterus transplantation was performed in nine women. 163 cervical biopsies (149 protocol, 14 follow-up) were taken to detect histopathological signs of rejection. Based on experience from animal experiments, we used a three-grade scoring system to evaluate biopsies systematically. Nine episodes of rejection were diagnosed in five patients: grade-1 in six episodes, grade-2 in two episodes and grade-3 in one episode. Treatment decisions were based on histopathology, and all rejection episodes were reversed after treatment. The biopsies were reviewed retrospectively and immunohistochemistry was performed to characterize the inflammatory infiltrates. A borderline category was introduced to avoid overtreatment of patients. Based on our review of all biopsies, we put forward a simple grading system for monitoring of rejection and to guide immunosuppressive treatment in uterus transplantation. This article is protected by copyright. All rights reserved.
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| 7. |
- Mölne, Johan, 1958, et al.
(författare)
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Rejection diagnosis after uterus transplantation
- 2019
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Ingår i: Uterus Transplantation. Brännsträm, M. (red.). - Cham : Springer. - 9783319941622 ; , s. 171-176
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Histopathology is currently the gold standard to diagnose rejection in transplanted organs. In contrast to other solid transplants, there is yet no knowledge about laboratory parameters or early clinical signs that may indicate rejection after uterus transplantation. However, the graft after uterus transplantation can be monitored by histological analysis of ectocervical biopsies. These biopsies are easily accessible at a standard gynecological examination, without putting the patient or graft at risk. Protocol biopsies are taken at regular time intervals after transplantation with subsequent follow-up biopsies in case of rejection to monitor treatment. We have developed and published a grading system for diagnosis of rejection on uterus transplantation biopsies, and this has been successfully applied during the initial Swedish trial with live donor transplantation and during the ongoing robotic-assisted uterus transplantation trial. © Springer Nature Switzerland AG 2020.
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