Uterus Transplant in Women With Absolute Uterine-Factor Infertility.

Importance: Uterus transplant in women with absolute uterine-factor infertility offers the possibility of carrying their own pregnancy. Objective: To determine whether uterus transplant is feasible and safe and results in births of healthy infants. Design, Setting, and Participants: A case series including 20 participants with uterine-factor infertility and at least 1 functioning ovary who underwent uterus transplant in a large US tertiary care center between September 14, 2016, and August 23, 2019. Intervention: The uterus transplant (from 18 living donors and 2 deceased donors) was surgically placed in an orthotopic position with vascular anastomoses to the external iliac vessels. Participants received immunosuppression until the transplanted uterus was removed following 1 or 2 live births or after graft failure. Main Outcomes and Measures: Uterus graft survival and subsequent live births. Results: Of 20 participants (median age, 30 years [range, 20-36]; 2 Asian, 1 Black, and 16 White), 14 (70%) had a successful uterus allograft; all 14 recipients gave birth to at least 1 live-born infant. Eleven of 20 recipients had at least 1 complication. Maternal and/or obstetrical complications occurred in 50% of the successful pregnancies, with the most common being gestational hypertension (2 [14%]), cervical insufficiency (2 [14%]), and preterm labor (2 [14%]). Among the 16 live-born infants, there were no congenital malformations. Four of 18 living donors had grade 3 complications. Conclusions and Relevance: Uterus transplant was technically feasible and was associated with a high live birth rate following successful graft survival. Adverse events were common, with medical and surgical risks affecting recipients as well as donors. Congenital abnormalities and developmental delays have not occurred to date in the live-born children. Trial Registration: ClinicalTrials.gov Identifier: NCT02656550.

New ERAS in liver transplantation - Past, present, and next steps.

There are parallels between the history of Enhanced Recovery after Surgery (ERAS) and liver transplantation. Both have been established and advanced by innovative individuals, often going against perceived wisdom and convention. Liver transplantation has traditionally been considered too complex for ERAS pathways, despite a small number of trials showing them to be both safe and of benefit. To date, there are very few randomized controlled trials and cohort studies publishing outcomes on liver transplant patients enrolled in comprehensive ERAS pathways. To progress our field, the 2022 International Liver Transplantation Society's Consensus Conference has created expert panels to analyze the evidence in 32 domains of the liver transplantation pathway using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to generate expert recommendations. These recommendations will be voted on by the international community to gain consensus using the Danish model, and create the ERAS4OLT.org Enhanced Recovery after Liver Transplantation Pathway.

Early outcomes of kidney transplant recipients from donors with severe SARS-CoV-2 pneumonia: A report of 5 cases.

BACKGROUND: Transplanting kidneys from donors with a recent history of severe SARS-CoV-2 pneumonia is uncommon due to concerns about the risk of viral transmission and the quality of kidneys from these donors. To date, there are no conclusive data on viral transmission from extrapulmonary solid organ transplants. Given the prevalence of SARS-CoV-2 infections in potential donors, shortage of kidneys available for transplantation, and low risk of viral transmission, we developed a clinical protocol for accepting kidneys from donors with recent severe SARS-CoV-2 pneumonia who demonstrate preserved kidney function. MATERIALS AND METHODS: We collected data on early outcomes of 5 kidney transplant recipients from 4 deceased donors hospitalized for severe SARS-CoV-2 infection. RESULTS: Donor creatinine ranged from 0.51 to 0.60 mg/dL and kidney donor profile index (KDPI) from 14 to 52%. Three of the five kidneys were from donation after circulatory death. All recipients were fully vaccinated, and 4/5 received post-exposure prophylactic monoclonal antibody treatment. While 3 recipients had delayed graft function, all had excellent graft function at 3 or 4 weeks post-operatively. None of the recipients displayed signs or symptoms of SARS-CoV-2 infection post-transplant. CONCLUSION: Our findings suggest that kidney grafts from donors with a recent history of severe SARS-CoV-2 infection but with preserved kidney function can be safely used and have good early outcomes.

Technological Advancements in Uterus Transplantation.

Uterus transplantation is barely a decade old and in a young, evolving field it is hard to identify "technological advances" since it is, in of itself, a technological advance. Nonetheless, one can still identify advances in diagnostic imaging that have improved donor screening to avoid graft losses, highlight the adoption of robotic surgery to make the living donor uterus procurement more minimally invasive, and look to a future of biotechnology like perfusion pumps and bioengineering such as synthetic uterus to increase donor supply. Additional technologies are on the horizon and promise to shape the field further.

Robotic Donor Hysterectomy Results in Technical Success and Live Births After Uterus Transplantation: Subanalysis Within the Dallas Uterus Transplant Study (DUETS) Clinical Trial.

Minimally invasive procurement of uterine grafts for transplantation can decrease living donor recovery time. We examined recipient outcomes for grafts procured by robotic-assisted donor hysterectomies with transvaginal extraction in the Dallas UtErus Transplant Study (DUETS). All 5 grafts were successfully transplanted. Recipients had a median 4.5-hour surgical time, 0.25 L estimated blood loss, and 4-day hospital stay. Four recipients had grade III surgical complications and three had acute cellular rejection. At 18 months, graft viability was 100%, with an 80% live birth rate. This report demonstrates the feasibility and reproducible success of using uterus grafts from living donors who underwent robotic-assisted donor hysterectomy.

The Evolution of Transplantation From Saving Lives to Fertility Treatment: DUETS (Dallas UtErus Transplant Study).

OBJECTIVE: We report the results of the first 20 uterus transplants performed in our institution. SUMMARY BACKGROUND DATA: Uterus transplantation (UTx) aims at giving women affected by absolute uterine-factor infertility the possibility of carrying their own pregnancy. UTx has evolved from experimental to an established surgical procedure. METHODS: The Dallas Uterus Transplant Study (DUETS) program started in 2016. The uterus was transplanted in orthotopic position with vascular anastomoses to the external iliac vessels and removed when 1 or 2 live births were achieved. Immunosuppression lasted only for the duration of the uterus graft. RESULTS: Twenty women, median age 29.7 years, enrolled in the study, with 10 in phase 1 and 10 in phase 2. All but 2 recipients had a congenital absence of the uterus. Eighteen recipients received uteri from living donors and 2 from deceased donors. In phase 1, 50% of recipients had a technically successful uterus transplant, compared to 90% in phase 2. Four recipients with a technical success in phase 1 have delivered 1 or 2 babies, and the fifth recipient with a technical success is >30 weeks pregnant. In phase 2, 2 recipients have delivered healthy babies and 5 are pregnant. CONCLUSIONS: UTx is a unique type of transplant; whose only true success is a healthy child birth. Based on results presented here, involving refinement of the surgical technique and donor selection process, UTx is now an established solution for absolute uterine-factor infertility.

DUETS (Dallas UtErus Transplant Study): Complete report of 6-month and initial 2-year outcomes following open donor hysterectomy.

INTRODUCTION: Uterus transplantation has shown success in treating women with uterine factor infertility who want to carry their own pregnancy. METHODS: We report the medical, sexual, and psychological outcomes of our first cohort of 13 living donor hysterectomies. As we have transitioned from open to robotically assisted hysterectomy, this report represents the complete series of open donor hysterectomies at our center, all with ≥6-month postoperative outcomes. RESULTS: The open donor hysterectomy had a median of a 6.5-hour surgical time, 0.8 L estimated blood loss, 6-day hospital stay, and 28-day sick leave. Three donors had a grade III or IV complications, one reported new-onset psychological symptoms, and 9 experienced transient sexual discomfort. All complications were addressed and resolved, and all donors returned to their presurgical social and physical activities. CONCLUSION: Since uterus transplantation is not life-saving or life-extending, the risks in living uterus donation must be weighed against the benefit of giving another woman the opportunity to give birth to her own child. This report provides data to support more detailed informed consent regarding the medical, psychological, and sexual complications of open living donor hysterectomy and allows for further evaluation of the ethical acceptability of this procedure.

Recipient characteristics and morbidity and mortality after liver transplantation.

BACKGROUND AND AIMS: Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States. We sought to identify an easily applicable set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within five years after liver transplantation. METHODS: We collected national (n = 31,829, 2002-2015) and center-specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5. Recipient factors associated with graft failure included: ventilator support (five patients; hazard ratio [HR] 1.59; 95% CI 1.48-1.72); recipient age >60 years (three patients; HR 1.29; 95% CI 1.23-1.36); hemodialysis (three patients; HR 1.26; 95% CI 1.16-1.37); diabetes (two patients; HR 1.20; 95% CI 1.14-1.27); or serum creatinine ≥1.5 mg/dl without hemodialysis (two patients; HR 1.15; 95% CI 1.09-1.22). RESULTS: Graft survival within five years based on points (any combination) was 77.2% (0-4), 69.1% (5-8) and 57.9% (>8). In recipients with >8 points, graft survival was 42% (model for end-stage liver disease [MELD] score <25) and 50% (MELD score 25-35) in recipients receiving grafts from donors with a donor risk index >1.7. In center-specific data within the first year, subjects with ≥5 points (vs. 0-4) had longer hospitalization (11 vs. 8 days, p <0.01), higher admissions for rehabilitation (12.3% vs. 2.7%, p <0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p <0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p = 0.03) within five years. CONCLUSION: The impact of co-morbidities in an MELD-based organ allocation system need to be reassessed. The proposed clinical tool may be helpful for center-specific assessment of risk of graft failure in non-HCV patients and for discussion regarding relevant morbidity in selected subsets. LAY SUMMARY: Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age >60 years, ventilator status, diabetes, hemodialysis and creatinine >1.5 mg/dl) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics leads to lower survival.

Eversion Bile Duct Anastomosis: A Safe Alternative for Bile Duct Size Discrepancy in Deceased Donor Liver Transplantation.

Bile duct size discrepancy in liver transplantation may increase the risk of biliary complications (BCs). The aim of this study was to evaluate the safety and outcomes of the eversion bile duct anastomosis technique in deceased donor liver transplantation (DDLT) with duct-to-duct anastomosis. A total of 210 patients who received a DDLT with duct-to-duct anastomosis from 2012 to 2017 were divided into 2 groups: those who had eversion bile duct anastomosis (n = 70) and those who had standard bile duct anastomosis (n = 140). BC rates were compared between the 2 groups. There was no difference in the cumulative incidence of biliary strictures (P = 0.20) and leaks (P = 0.17) between the 2 groups. The BC rate in the eversion group was 14.3% and 11.4% in the standard anastomosis group. All the BCs in the eversion group were managed with endoscopic stenting. A severe size mismatch (≥3:1 ratio) was associated with a significantly higher incidence of biliary strictures (44.4%) compared with a 2:1 ratio (8.2%; P = 0.002). In conclusion, the use of the eversion technique is a safe alternative for bile duct discrepancy in DDLT. However, severe bile duct size mismatch may be a risk factor for biliary strictures with such a technique.

Living uterus donation and transplantation: experience of interest and screening in a single center in the United States.

BACKGROUND: Little is known about attitudes toward uterus donation and transplantation in society and the interest of the women the treatment is aimed to assist. OBJECTIVE: This study examined the interest of recipients and living donors in our uterus transplantation program; it describes the screening protocol we developed and the results of the screening and reports demographic data and characteristics of screened candidates. STUDY DESIGN: Initial screening and evaluation included physical examinations by a gynecologist and a transplant surgeon; psychological evaluation; imaging (x-ray, computed tomography, ultrasound); blood tests; immunological testing; viral, bacterial, and fungal testing; drug screen; hormonal testing; Papanicolau smear; urinalysis; and electrocardiogram. For selected recipients, the process also included in vitro fertilization. RESULTS: A total of 351 women contacted our department with interest in participating in uterus transplantation; 272 were potential recipients and 79 were potential donors. Among these women, 179 potential recipients and 62 potential donors continued the evaluation after the initial telephone screening. The mean age of the donor candidates was 40 years; all had completed their own family, and 80% were nondirected. Most recipient candidates (92%) had an anatomical lack of the uterus, and of these, 36% had a congenital malformation. The women with a congenital uterine absence were in general younger than the women in the group whose uterus had been removed (mean of 28 and 33 years, respectively). In every step of the initial screening and evaluation process, there were donor and recipient candidates that chose not to continue the process. The reasons for self-withdrawal after expressing interest were not returning phone calls or e-mails (17 donors and 76 recipients); after initial phone screening, no longer interested (1 donor and 9 recipients); in step 1, health history questionnaire not returned after 1 reminder (10 donors and 9 recipients); step 2, not right in their current life situation (2 donors and 2 recipients), and in step 3, chose another way to achieve motherhood (1 recipient). Most donor and recipient candidates (52% and 78%, respectively) could be screened out (because of self-withdrawal or transplant team's decision) during the noninvasive and cost-efficient initial screening. CONCLUSION: Our initial experience shows a great interest in participating in a trial of uterus transplantation by both potential recipients and donors. It is the first study to show interest in nondirected donation. A sufficient but thoughtful screening process of living donors and recipients is essential and should aim both to assure donor/recipient safety and to provide good quality grafts.

Tumor biology and pre-transplant locoregional treatments determine outcomes in patients with T3 hepatocellular carcinoma undergoing liver transplantation.

Liver transplantation is the optimal treatment for patients with hepatocellular carcinoma (HCC) and cirrhosis. This study was conducted to determine the impact of pre-transplant locoregional therapy (LRT) on HCC and our institution's experience with expansion to United Network of Organ Sharing Region 4 T3 (R4T3) criteria. Two hundred and twenty-five patients with HCC (176 meeting Milan and 49 meeting R4T3 criteria) underwent liver transplantation from 2002 to 2008. Compared with the Milan criteria, HCCs in R4T3 criteria displayed less favorable biological features such as higher median alpha-fetoprotein level (21.9 vs. 8.5 ng/mL, p = 0.01), larger tumor size, larger tumor number, and higher incidence of microvascular invasion (22% vs. 5%, p = 0.002). As a result, patients meeting Milan criteria had better five-yr survival (79% vs. 69%, p = 0.03) and a trend toward lower HCC recurrence rates (5% vs. 13%, p = 0.05). Pre-transplant LRT did not affect post-transplant outcomes in patients meeting Milan criteria but did result in lower three-yr HCC recurrence (7% vs. 75%, p < 0.001) and better three-yr survival (p = 0.02) in patients meeting R4T3 criteria. Tumor biology and pre-transplant LRT are important factors that determine the post-transplant outcomes in patients with HCC who meet R4T3 criteria.

Implications of a positive crossmatch in liver transplantation: a 20-year review.

Whether a positive crossmatch result has any relevance to liver transplantation (LT) outcomes remains controversial. We assessed the impact of a positive crossmatch result on patient and graft survival and posttransplant complications. During a 20-year period, 2723 LT procedures with crossmatch results were identified: 2479 primary transplants and 244 retransplants. The rates of positive B cell and T cell crossmatches were 10.1% and 7.4%, respectively, for primary transplants and 14.6% and 6.4%, respectively, for retransplants (P = 0.049 for a B cell crossmatch). Across all primary transplants, females (P < 0.001) and patients with autoimmune hepatitis (P < 0.001) had greater frequencies of positive crossmatches. There was no effect from race or age. For both primary transplants and retransplants, patient survival and graft survival were not affected by the presence of a positive crossmatch. With respect to posttransplant complications, there were no differences in rejection episodes (hyperacute, acute, or chronic) or technical complications (biliary and vascular) between negative and positive crossmatch groups. However, there were significant differences in the pathological findings of preservation injury (PI) on liver biopsy samples taken at the time of transplantation and within the first week of transplantation (P = 0.003 for B cells and P = 0.03 for T cells). In summary, a positive crossmatch had no significant impact on patient survival or graft outcomes. However, there was a significantly higher incidence of PI in primary LT recipients with a positive crossmatch. This finding is important for a broader understanding of PI, which may include a significant immunological component.

Indications for combined liver and kidney transplantation: propositions after a 23-yr experience.

The frequency of combined liver and kidney transplants (CLKT) persists despite the pronounced scarcity of organs. In this review, we sought to ascertain any factors that would reduce the use of these limited commodities. Seventy-five adult CLKT were performed over a 23-yr period at our center, 29 (39%) of which occurred during the Model for End-stage Liver Disease (MELD) era. Overall, patient survival rates were 82%, 73%, and 62% at one, three, and five yr, respectively. There was no difference in patient survival based either on pre-transplant hemodialysis status or by glomerular filtration rate (GFR) at the time of transplant. Patients undergoing a second CLKT or a liver retransplantation at the time of CLKT had a survival rate of 30% at three months. In the MELD era, patient survival was unchanged (p = NS) despite an older recipient population (p = 0.0029) and a greater number of hepatitis C patients (p = 0.0428). In summary, patients requiring liver retransplantation with concomitant renal failure should be denied CLKT. Renal allografts may also be spared by implementing strict criteria for renal organ allocation (GFR < 30 mL/min at the time of evaluation) and considering the elimination of preemptive kidney transplantation in CLKT.

Twenty years of follow-up of aortohepatic conduits in liver transplantation.

Arterial problems remain a formidable challenge in liver transplantation. In many situations, an aortohepatic conduit can provide a solution. No long-term results (over 5 years) have been reported. This study was designed to assess the impact of aortohepatic conduits on graft survival after liver transplantation and the safety of aortohepatic conduits and to establish the long-term results (up to 20 years) of aortohepatic conduits. Data from 2346 adult liver transplants were prospectively collected into the computerized database and analyzed. In the majority of cases, arterial conduits were constructed from the donor iliac artery obtained at the liver retrieval. Aortohepatic conduits were required in 149 (6.4%) first transplants. The long-term graft survival after liver transplantation using aortohepatic conduits was excellent and comparable to that of the control group. The graft survival was 59% with the conduit versus 67% without the conduit at 5 years of follow-up, 50% versus 52% at 10 years, and 33% versus 35% at 15 years. With up to 20 years of follow-up, there was no statistically significant difference in graft survival, patient survival, hepatic artery complications, or biliary complications. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without aortohepatic conduits. In conclusion, in experienced hands, aortohepatic conduits can be used safely for liver transplantation with no negative impact on long-term graft survival, patient survival, hepatic artery complications, or biliary complications. Excellent long-term results can be obtained.

Late acute rejection after liver transplantation impacts patient survival.

Hepatic allograft rejection still remains an important problem following liver transplantation. Early acute rejection, occurring within three months of transplant, is a common event and usually of lesser significance with respect to prognosis than other non-immune-related post-transplant morbidities. However, little is known about late acute rejection (LAR) including factors affecting its occurrence and long-term outcome. In this study, we analyzed LAR including the incidence, clinical risk factors, patient survival, and graft survival. LAR was defined as acute cellular rejection later than six months after liver transplant. Adult patients who had a minimum of 24 months of graft survival were included in this study. A total of 1604 case records of consecutive adult patients (over age 18 yr) who underwent liver transplant between 1985 and 2003 were reviewed. Of the 1604 patients, 305 (19.0%) developed LAR. Patients with primary diagnoses of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis had higher incidences of LAR, while patients with metabolic disease and retransplant had lower incidence of LAR (p = 0.0024). The LAR group had more female and younger recipients than the no LAR group (p = 0.0026, p = 0.0131, respectively). Patient survival as well as graft survival were significantly lower in the LAR group (p = 0.0083, p = 0.0075, respectively). PTLD was the only significant independent predictor of late rejection. The careful management and treatment of PTLD, especially immunosuppressive management, is important to prevent LAR, which is related to poorer patient survival.