Radiologic Evaluation of Uterine Vasculature of Uterus Transplant Living Donor Candidates: DUETS Classification.

Uterus transplantation is a treatment solution for women suffering from absolute uterine factor infertility. As much as 19.5% of uterus-transplanted patients underwent urgent graft hysterectomy due to thrombosis/hypoperfusion. The necessity to identify candidates with high-quality uterine vasculature is paramount. We retrospectively evaluated and compared the imaging results with actual vascular findings from the back table. In this article, we present a novel radiologic grading scale (DUETS classification) for evaluating both uterine arteries and veins concerning their suitability for uterus procurement and transplantation. This classification defines several criteria for arteries (caliber, tapering, atherosclerosis, tortuosity, segment, take-off, and course) and veins (caliber, tapering, plethora, fenestrations, duplication/multiplicity, dominant route of venous drainage, radiologist's confidence with imaging and assessment). In conclusion, magnetic resonance angiography can provide reliable information on uterine venous characteristics if performed consistently according to a well-established protocol and assessed by a dedicated radiologist. The caliber of uterine arteries seems to be inversely related to the time passed since the last delivery. We recommend that the radiologist comments on the reliability and confidence of the imaging study. It cannot be over-emphasized that the most crucial aspect of surgical imaging is the necessity of high-quality communication between a surgeon and a radiologist.

A multi-institutional study of renal outcomes and renal-related pregnancy outcomes in uterus transplant recipients.

Uterus transplantation (UTx) is an effective treatment option for uterine factor infertility. However, the need for immunosuppression and congenital renal anomalies that coexist with uterine agenesis in about 30% of women with Mayer-Rokitansky-Kuster-Hauser syndrome create a risk for renal dysfunction. We therefore examined renal function trajectory and related pregnancy complications in an international cohort of 18 UTx recipients from September 2016-February 2020 who had at least one live birth. All UTx recipients had a diminution in their renal function that was apparent starting at 30 days posttransplant and in half the reduction in eGFR was at least 20%; the decrease in eGFR persisted into the early post-partum period. Half met criteria for Stage 1 acute kidney injury (AKI) as defined by the AKI Network criteria during their pregnancy. Overall, 28% of UTx recipients developed pre-eclampsia. eGFR was lower at embryo transfer and throughout pregnancy among those who developed pre-eclampsia, reaching statistical significance at week 16 of pregnancy. This effect was independent of tacrolimus levels. Mean eGFR remained significantly lower in the first 1-3 months after delivery. In the subgroup who reached 12 months of postpartum follow up and had a graft hysterectomy (n = 4), there was no longer a statistical difference in eGFR (pretransplant 106.7 ml/m ± 17.7 vs. 12 mos postpartum 92.6 ml/m ± 21.7, p = .13) but the number was small. Further study is required to delineate long term renal risks for UTx recipients, improve patient selection, and make decisions regarding a second pregnancy.

Human Uterus Transplantation from Living and Deceased Donors: The Interim Results of the First 10 Cases of the Czech Trial.

INTRODUCTION: Uterus transplantation (UTx) is a rapidly evolving treatment of uterine-factor infertility. We report the results of the first 10 UTx procedures performed at our institution. METHODS: The program started in April 2016 as a two-arm study comparing the efficacy of UTx from live donors (LD) and deceased donors (DD). RESULTS: Between April 2016 and April 2018, we performed five DD UTx and five LD UTx. Two grafts had to be removed early due to thrombosis. One graft was removed due to chronic rejection and previous herpes simplex infection at month 7. Graft survival is 70% at one year. Recipient survival is 100% at two years. Live donor survival is 100% at three years. Three live-births have been achieved, two from a LD and one from a graft from a nulliparous DD. Vaginal anastomotic stenosis occurred in 63% (5/8) of grafts. Self-expanding stents have shown preliminary suitability for the treatment of vaginal stenosis. Three recipients developed severe acute rejection. CONCLUSION: The interim results of our study demonstrate mid-term viability in 70% of grafts. The LD UTx produced two live births and the DD UTx produced one live birth. Nulliparous donors should be considered for donation.

Live Birth Following Uterine Transplantation From a Nulliparous Deceased Donor.

BACKGROUND: Nulliparous uterine grafts have never been used in uterus transplantation (UTx), possibly due to presumed infertility. Our objective was to verify the feasibility of nulliparous uterine graft transplantation. METHODS: The Czech Uterus Transplant Trial (registered under ClinicalTrials.gov, identifier NCT03277430) is a 2-arm trial comparing the efficacy of deceased donor (DD) versus live-donor uterus transplant (10 patients in both arms). A 25-year-old patient suffering from inborn absolute uterine factor infertility underwent a DD uterus transplant. The donor was a 20-year-old nulliparous brain-dead donor. RESULTS: The transplant procedure was uneventful. The posttransplant period was complicated by (1) recurrent episodes of acute cellular rejection, (2) neutropenia necessitating the administration of granulocyte colony-stimulating factor, (3) vaginal anastomotic stenosis treated with the insertion of a self-expanding stent, (4) the concurrence of Clostridium difficile colitis and acute appendicitis, and (5) temporary renal function impairment of a combined cause. Two years after the UTx, after the fourth embryo transfer, the patient became pregnant. Apart from gestational diabetes mellitus, the pregnancy was uneventful. Due to preterm contractions, delivery was achieved via caesarean section at gestational age 34 + 6 years. The postoperative course was uneventful for both the mother and the newborn. CONCLUSIONS: Herein, we report the first live birth after a DD UTx in Europe. This report provides a proof of concept that nulliparous uteri may present a suitable source of uterine grafts for UTx. Stenting may serve as a feasible treatment method for vaginal anastomotic stenosis.

Hybrid Repair Combined with Fresh Arterial Allograft Extra-Anatomical Reconstruction: The Treatment of Infrarenal Abdominal Aneurysm above an Aortobifemoral Bypass Complicated by an Infected Pseudoaneurysm in the Left Groin.

INTRODUCTION: A 72-year-old male patient was admitted into our centre with large infected pseudoaneurysm (PSA) in the left groin. The patient underwent a CT angiography (CTA) that confirmed a large partly thrombosed 6.5 × 5.5 cm PSA in the left groin arising from the distal anastomosis of the aortobifemoral bypass (ABF). Furthermore, the CTA revealed 11 cm juxtarenal abdominal aortic aneurysm (JAAA) from which the proximal anastomosis of the ABF was arising. METHOD: Aorto-uni-iliac stent graft Cook was placed from the right groin trough native severely stenotic right iliac arteries with proximal landing zone below the renal arteries, excluding the JAAA and the ABF. The distal landing zone was in the common iliac artery maintaining patent right internal iliac artery. Afterwards, a femoro-femoral crossover bypass from right to left was performed using a fresh arterial allograft. Postprocedurally, the hospital stay was uneventful. The left groin PSA cultures came positive for Staphylococcus epidermidis and Corynebacterium tuberculostearicum, both sensitive to vancomycin and rifampicin. RESULT: The patient underwent intravenous ATB treatment with vancomycin for two weeks, followed by four weeks of oral rifampicin. The patient was discharged on the 20th postoperative days. CONCLUSION: Hybrid repair combining aortic stent graft and extra-anatomical bypass in the treatment of infected distal parts of an aortofemoral bypass is an acceptable treatment modality.

The Effect of Different Thawing Rates on Cryopreserved Human Iliac Arteries Allograft's Structural Damage and Mechanical Properties.

INTRODUCTION: The rate of thawing of cryopreserved human iliac arteries allografts (CHIAA) directly affects the severeness of structural changes that occur during this process. METHOD: The experiment was performed on ten CHIAA. The 10% dimethylsulphoxide in 6% hydroxyethyl starch solution was used as the cryoprotectant; all CHIAA were cooled at a controlled rate and stored in the vapor phase of liquid nitrogen (-194°C). Two thawing protocols were tested: (1) placing the CHIAA in a water bath at 37°C, and (2) the CHIAA were thawed in a controlled environment at 5°C. All samples underwent analysis under a scanning electron microscope. Testing of the mechanical properties of the CHIAA was evaluated on a custom-built single axis strain testing machine. Longitudinal and circumferential samples were prepared from each tested CHIAA. RESULTS: Ultrastructural analysis revealed that all five CHIAA thawed during the thawing protocol 1 which showed significantly more damage to the subendothelial structures when compared to the samples thawed in protocol 2. Mechanical properties: Thawing protocol 1-longitudinal UTS 2, 53 ± 0, 47 MPa at relative strain 1, 27 ± 0, 12 and circumferential UTS 1, 94 ± 0, 27 MPa at relative strain 1, 33 ± 0, 09. Thawing protocol 2-longitudinal ultimate tensile strain (UTS) 2, 42 ± 0, 34 MPa at relative strain 1, 32 ± 0, 09 and circumferential UTS 1, 98 ± 0, 26 MPa at relative strain 1, 29 ± 0, 07. Comparing UTS showed no statistical difference between thawing methods. CONCLUSION: Despite the significant differences in structural changes of presented thawing protocols, the ultimate tensile strain showed no statistical difference between thawing methods.

Human uterine vasculature with respect to uterus transplantation: A comprehensive review.

Due to the novelty of uterus transplantation, data on preferable inflow and outflow of the graft are limited. This paper reviews the technique, type of vessels and the outcome. A systematic search of the PubMed database was conducted. We extracted and analyzed data on the arteries and veins utilized, types of anastomosis, types of donors, complications and the outcome. Thirty eight sources reported 51 human uterine transplantations, 10 graft thromboses and 25 live births. Inflow was established with two uterine arteries (UA) with/without the anterior division of the internal iliac artery in 62% (n = 31) of cases, two UA arteries with a segment/patch of the internal iliac artery in 34% (n = 17) of cases or two UA with a conduit in 4% of cases (n = 2). Both cases with a conduit developed thrombosis (n = 2). Arterial thrombosis/ischemia developed in 8 of the 51 cases. In 50% of cases with arterial thrombosis, atherosclerosis was identified as a possible cause. Outflow was established by two internal iliac veins with patches/segments in 27.5% of cases (n = 14) followed by two utero-ovarian veins in 25.5% (n = 13). Venous thrombosis occurred in 3 of the 51 cases. Uterine arteries with/without anterior division of the internal iliac artery were the most frequent arteries used for inflow and produced the highest patency rate. The presence of atherosclerosis and complex arterial reconstruction was associated with a high rate of arterial thrombosis. None of the veins utilized in the procedures appeared to be superior. There are insufficient data to draw a definite conclusion.

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

BACKGROUND: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). METHODS: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. RESULTS: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. CONCLUSION: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Uterus transplant graft's arterial atherosclerotic remodeling veracity.

BACKGROUND: Uterus transplantation is a complex, multi-step experimental procedure used for the treatment of uterus absence or uterus anomaly that prevents embryo implantation or pregnancy completion. METHOD: To date, only 51 uterus transplants worldwide had been performed. When simplified, it is vascularized composite allograft transplantation. While it is still an experimental procedure with encouraging results for the future, there are still many issues that have to be clarified. The most serious complications of uterus transplantation are graft rejection or grafts vascular failure. RESULTS: So far, no reference to the atherosclerotic arterial infiltration of the uterus arteries was suggested and studied as one of the main causes of graft's failure. CONCLUSION: In this review we summarized current knowledge and possible role of uterus arterial damage, including atherosclerotic changes on the graft's survival.

Acute appendicitis in a patient after a uterus transplant: A case report.

BACKGROUND: Acute appendicitis in a solid organ transplant recipient is a rare occurrence, and experience remains limited. Appendicitis in uterine transplant recipients has never been reported. Immunocompromised patients with acute abdomen often present late and with attenuated symptoms. The differential diagnosis in a transplanted patient is broad and challenging due to possible existing complications associated with the graft, effects of immunosuppression, and altered anatomical relations. CASE SUMMARY: A 26-year-old woman suffering from absolute uterine factor infertility received a uterus transplant. In the post-transplant period, she suffered from leukopenia and recurrent acute cellular rejection. Her compliance was suboptimal. She travelled to an exotic destination despite the physician's recommendation not to do so. Following her vacation, she presented with abdominal discomfort, nausea and diarrhoea. There was no sign of acute abdomen; the abdominal ultrasound was negative on day 0. Clostridium difficile colitis was verified and treated with perorally administered vancomycin. On day 4, the discomfort changed to pain; the ultrasound scan revealed a finding suggestive of appendicitis. Surgical exploration revealed perforated appendicitis, and appendectomy was performed. From a surgical point of view, the patient's follow-up was uneventful. The patient underwent a successful embryo transfer 6 months after the appendectomy. The patient gave birth to a healthy boy at the 35th week of gestation. CONCLUSION: A high index of suspicion of an atypical course and symptomatology of acute abdomen should be maintained in immunosuppressed patients.

Revaluation and lessons learned from the first 9 cases of a Czech uterus transplantation trial: Four deceased donor and 5 living donor uterus transplantations.

Although uterus transplantation is still in the experimental stage, it has promising potential as a treatment for women with absolute uterine factor infertility based on the childbirths from living donor trials conducted in Sweden and the United States. We report the main characteristics and perioperative and postoperative courses of both recipients and donors following 4 deceased donor and 5 living donor uterus transplantations. Three main priorities differentiate this study from the previously reported uterus transplantations. First, clinical experience with the largest worldwide group of deceased donor uterine transplants is described. Second, in the majority of living donor uterine recipients, only 2 ovarian veins were used for venous blood outflow. All of these recipient procedures were surgically successful, and follow-up posttransplant ultrasound examinations revealed normal uterine blood supply and outflow. Third, in only one living and one deceased donor recipient, the transplanted uterus relied on only 2 uterine veins for venous outflow with a 50% surgical success rate. In all other recipients, 2 uterine and 2 ovarian veins were utilized. Although a successful pregnancy has not yet been achieved, the presented surgical and functional results of our trial are promising.