A study protocol for live and deceased donor uterus transplantation as a treatment for women with uterine factor infertility.

AIM: Uterus transplantation (UTx) is an emerging treatment option for women with uterine factor infertility (UFI) or the absence of a functional uterus. This is the study protocol for the first human UTx clinical trial in Australia. MATERIALS AND METHODS: This protocol outlines the approved training program used to plan, diagnose, screen, and treat patients who may be eligible for UTx using living and deceased donors. This multi-site clinical research study includes three tertiary hospital sites within New South Wales (NSW), Australia - Prince of Wales, Royal Hospital for Women and Westmead Hospitals. Our UTx protocol is based on that used by our collaborative partner, the inaugural UTx team in Gothenburg, Sweden. The Swedish UTx team provides ongoing preceptorship for the Australian UTx team. Ethics approval for six UTx procedures using living or deceased donors (Western Sydney Local Health District Human Research Ethics Committee: 2019/ETH138038) was granted in 2020. RESULTS: Results from surgeries and live births will be published. Data will be prospectively entered into the registry of the International Society of Uterus Transplantation (ISUTx), a sub-section of The Transplantation Society (TTS). TRIAL ID: ACTRN12622000917730. DISCUSSION: A multidisciplinary research team has been formed between three tertiary hospitals in Sydney - The Royal Hospital for Women, Prince of Wales and Westmead Hospitals; and with the Swedish UTx, University of Gothenburg. The Swedish team pioneered animal and human UTx studies since 1998, including publishing the first live birth after UTx. (1) This Australian trial commenced in January 2023. CONCLUSION: Uterus transplantation gives women with UFI the opportunity to be gestational and genetic mothers. It is a complex procedure for both the donor and recipient, with medical and surgical risks. An extensive multidisciplinary approach is required to optimise patient safety and graft outcomes. This protocol outlines our Australian UTx team strategy for screening, recruitment, surgical approach, and clinical management of UTx recipients and donors.

Cardiovascular risk management in the peri-operative setting.

Peri-operative cardiovascular events occur in up to 3% of patients undergoing non-cardiac surgery. Accurate cardiovascular risk assessment is important in the peri-operative setting, as it allows informed and shared decisions regarding the appropriateness of proceeding with surgery, guides surgical and anaesthetic approaches, and may influence the use of preventive medications and post-operative cardiac monitoring. Quantitative risk assessment may also inform a reconsideration of choosing a more limited lower risk type of surgery, or conservative management. Pre-operative cardiovascular risk assessment starts with clinical assessment and should include an estimate of functional capacity. Specialised cardiac investigations are rarely indicated specifically to assess pre-operative cardiovascular risk. The decision regarding cardiac investigations is influenced by the nature, extent and urgency of surgery. The strategy of performing pre-operative revascularisation to improve post-operative outcomes is not evidence-based and recent international guidelines recommend against this.

Insulating jackets thermally protect kidneys in an ex vivo model of second warm ischemia.

BACKGROUND: Kidney transplantation is the current optimal treatment for suitable patients with end-stage renal disease. The second warm ischemic time (SWIT) is known to negatively impact delayed graft function, and long-term graft survival, and methods are required to ameliorate the impacts of SWIT on transplantation outcomes. MATERIALS AND METHODS: This study primarily focused on determining the effect of a novel thermally insulating jacket on the thermal profile of the human kidney and quantifying the reduction in thermal energy experienced using this device (KPJ™). An ex vivo simulated transplantation model was developed to determine the thermal profiles of non-utilized human kidneys with and without KPJ™ (n = 5). Control kidney temperature profiles were validated against the temperature profiles of n = 10 kidneys during clinical kidney transplantation. RESULTS: Using the ex-vivo water bath model, the thermally insulated human kidney reached the 15°C metabolic threshold temperature at 44.5 ± 1.9 min (vs control: 17.3 ± 1.8 min (p = 0.00172)) and remained within the 18°C threshold until 53.3 ± 1.3 min (vs control: 20.9 ± 2.0 min (p = 0.002)). The specific heat capacity of KPJ™ protected kidney was four-fold compared to the control kidney. The clinical temperature audit, closely correlated with the water bath model, hence validating this ex-vivo human kidney transplant model. CONCLUSION: Intraoperative thermal protection is a simple and viable method of reducing the thermal injury that occurs during the SWIT and increasing the specific heat capacity of the system. Such technology could easily be translated into clinical kidney transplant practice.

Deceased donor availability for uterus transplantation in Australia.

BACKGROUND: Uterus transplantation is an emerging treatment option for uterine factor infertility. Most uterus transplantation research programs use living donors, although this comes with considerable surgical and psychological risks and not all women desiring uterus transplantation will have an available living donor. A deceased donor program eliminates donor risks; however, the availability of deceased uterus donors is currently unknown in Australia. AIMS: To establish the feasibility of a deceased donor uterus transplantation program in Australia and consider expanded inclusion criteria for this model. MATERIALS AND METHODS: A retrospective review of the New South Wales (NSW) Organ and Tissue Donation Service database was undertaken to identify potential deceased uterus donors, with comparison to the broad deceased donor inclusion criteria from three international uterus transplantation trials including female, brain-dead, multi-organ donation, no major abdominal surgery, and <60 years of age. RESULTS: Between January 1, 2018, and December 31, 2022, 648 deceased donors were available in NSW. Of these, 43% (279/648) were female and 67% of the women (187/279) were also multi-organ donors. When the brain-dead donor-only and age criteria (<60 years) were applied, a total of 107 deceased donors met the available criteria for uterus transplantation, with an average of 21 deceased donors per year in NSW. CONCLUSIONS: There appears to be adequate deceased donor organ availability to establish a deceased uterus transplantation program in NSW, Australia. Should interest in uterus transplantation increase, including criteria such as older and nulliparous donors could increase organ availability for a uterus transplantation program.

The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration.

AIMS: The aim is to report the results of Australia's first uterus transplantation (UTx). METHODS: Following long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team. RESULTS: This is the first UTx procedure to occur in Australia, involving a mother donating her uterus to her daughter. The total operative time for the donor was 9 h 54 min. Concurrently, recipient surgery was synchronised to minimise graft ischaemic time, and the total operative time for the recipient was 6 h 12 min. Surgery was by laparotomy in the LD and recipient. The total warm ischaemic time of the graft was 1 h 53 min, and the cold ischaemic time was 2 h 17 min (total ischaemic time 4 h 10 min). The patient's first menstruation occurred 33 days after the UTx procedure. CONCLUSION: Twenty-five years of Swedish and Australian collaboration has led to Australia's first successfully performed UTx surgery at The Royal Hospital for Women, Sydney, Australia.

A Systematic Review and Meta-Analysis of the Significance of Body Mass Index on Kidney Cancer Outcomes.

PURPOSE: Obesity is a well-known risk factor for kidney cancer incidence. However, a number of studies have demonstrated more favorable kidney cancer prognosis in patients with elevated body mass index conferring a survival advantage, termed the "obesity paradox." We aimed to evaluate the association between body mass index and kidney cancer outcomes (progression-free survival, cancer specific survival and overall survival). MATERIALS AND METHODS: A computerized systematic search of Medline®, Embase®, ProQuest®, PubMed® and Google Scholar™ for literature published in English was performed between its inception and December 2018, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for reporting. RESULTS: Overall, 34 publications comprising a total of 50,717 patients were included in the analysis. The majority assessed the association between body mass index and cancer specific survival. Overweight and obese patients were associated with improved cancer specific survival compared to patients with normal body mass index (HR 0.85, 95% CI 0.79-0.93). A similar trend was demonstrated for progression-free survival (HR 0.68, 95% CI 0.59-0.78) and overall survival (HR 0.66, 95% CI 0.55-0.79). On the contrary, the underweight group was associated with inferior cancer specific survival (HR 2.16, 95% CI 1.15-4.04). Main drawbacks limiting the interpretation were the retrospective design in the majority of studies, heterogeneity in study population, body mass index classification and covariates in multivariate analysis. CONCLUSIONS: This is the largest systematic review evaluating the potential phenomenon of the obesity paradox in kidney cancer outcomes. It demonstrated a favorable effect of body mass index on kidney cancer outcomes. However, due to significant heterogeneity of studies, multicenter prospective studies and further research on the fundamental biological mechanisms are warranted to confirm the significance of body mass index on kidney cancer prognosis.

Paediatric kidney transplants from donors aged 1 year and under: an analysis of the Australian and New Zealand Dialysis and Transplant Registry from 1963 to 2018.

Kidneys from very small donors have the potential to significantly expand the donor pool. We describe the collective experience of transplantation using kidneys from donors aged ≤1 year in Australian and New Zealand. The ANZDATA registry was analysed on all deceased donor kidney transplants from donors aged ≤1 year. We compared recipient characteristics and outcomes between 1963-1999 and 2000-2018. From 1963 to 1999, 16 transplants were performed [9 (56%) adults, 7 (44%) children]. Death-censored graft survival was 50% and 43% at 1 and 5 years, respectively. Patient survival was 90% and 87% at 1 and 5 years, respectively. From 2000 to 2018, 26 transplants were performed [25 (96%) adults, 1 (4%) children]. Mean creatinine was 73 µmol/l ±49.1 at 5 years. Death-censored graft survival was 85% at 1 and 5 years. Patient survival was 100% at 1 and 5 years. Thrombosis was the cause of graft loss in 12% of recipients in the first era from 1963 to 1999, and 8% of recipients in the second era from 2000 to 2018. We advocate the judicious use of these small paediatric grafts from donors ≤1 year old. Optimal selection of donor and recipients may lead to greater acceptance and success of transplantation from very young donors.

Relative survival and quality of life benefits of pancreas-kidney transplantation, deceased kidney transplantation and dialysis in type 1 diabetes mellitus-a probabilistic simulation model.

For patients with type 1 diabetes mellitus who progress to the point of requiring renal replacement therapy, the relative benefits of simultaneous pancreas and kidney transplantation (SPK) and deceased donor kidney transplantation across different age categories compared to dialysis are uncertain. Using Australian and New Zealand registry data from 2006 to 2016, a probabilistic Markov model (n = 10 000) was built comparing patient survival between SPK and deceased donor kidney transplantation with dialysis. Compared to dialysis, the average life years saved (LYS) and quality-adjusted life years (QALY) for SPK and deceased donor kidney transplantation were 5.48 [95% CI 5.47, 5.49] LYS and 6.48 [6.47, 6.49] QALY, and 3.38 [3.36, 3.40] LYS and 2.46 [2.45, 2.47] QALY, respectively. For recipients aged 50 years or younger, receiving a deceased donor kidney, the average incremental gains compared to dialysis were 4.13 [4.10, 4.16] LYS and 2.99 [2.97, 3.01] QALY, and for recipients older than 50 years, 3.05 [3.02, 3.08] LYS and 2.25 [2.23, 2.27] QALY. Compared to dialysis, SPK transplantation incurs the greatest benefits in LYS and QALY for patients with type 1 diabetes requiring renal replacement therapy. Patients older than 50 years still experience survival benefits from deceased donor kidney transplantation compared to dialysis.

Weekend effect on early allograft outcome after kidney transplantation- a multi-centre cohort study.

Weekend surgery may be associated with a higher risk of early complications, but the effect of the timing of kidney transplant surgery on early allograft outcome remains uncertain. The aim of this study is to evaluate whether the association between weekend transplant surgery and allograft failure was modified by prevalent vascular disease. Using data from the Australia and New Zealand Dialysis and Transplant registry, we examined the association between weekend status and 90-day and 1-year allograft failure in deceased donor transplant recipients between 1994-2012. Two-way interaction between vascular disease and weekend status was examined. Of 6622 recipients, 1868 (28.2%) received transplants during weekends. Compared with weekday transplants, weekend transplants were associated with an adjusted hazard ratio (HR) for 90-day and 1-year allograft failure of 0.99 (0.78-1.25; P = 0.917) and 0.93 (0.76-1.13, P = 0.468), respectively. There was a significant interaction between prevalent vascular disease and weekend status for 90-day allograft failure (Pinteraction = 0.008) but not at 1-year, such that patients with vascular disease were more likely to experience 90-day allograft failure if transplanted on weekend (versus weekdays), particularly failures secondary to vascular complications. Timing of transplantation does not impact on allograft outcome, although those with vascular disease may benefit from more intensive post-transplant follow-up for potential vascular complications.

Aortic Versus Dual Perfusion for Retrieval of the Liver After Brain Death: A National Registry Analysis.

There is lack of consensus in the literature regarding the comparative efficacy of in situ aortic-only compared with dual (aortic and portal venous) perfusion for retrieval and transplantation of the liver. Recipient outcomes from the Australia/New Zealand Liver Transplant Registry (2007-2016), including patient and graft survival and causes of graft loss, were stratified by perfusion route. Subgroup analyses were conducted for higher-risk donors. A total of 1382 liver transplantation recipients were analyzed (957 aortic-only; 425 dual perfusion). There were no significant differences in 5-year graft and patient survivals between the aortic-only and dual cohorts (80.1% versus 84.6% and 82.6% versus 87.8%, respectively) or in the odds ratios of primary nonfunction, thrombotic graft loss, or graft loss secondary to biliary complications or acute rejection. When analyzing only higher-risk donors (n = 369), multivariate graft survival was significantly less in the aortic-only cohort (hazard ratio, 0.49; 95% confidence interval, 0.26-0.92). Overall, there was a trend toward improved outcomes when dual perfusion was used, which became significant when considering higher-risk donors alone. Inferences into the ideal perfusion technique in multiorgan procurement will require further investigation by way of a randomized controlled trial, and outcomes after the transplantation of other organs will also need to be considered.

A systematic review and meta-analysis of cold in situ perfusion and preservation of the hepatic allograft: Working toward a unified approach.

The efficacy of cold in situ perfusion and static storage of the liver is a possible determinant of transplantation outcomes. The aim of this study was to determine whether there is evidence to substantiate a preference for a particular perfusion route (aortic or dual) or perfusion/preservation solution in donation after brain death (DBD) liver transplantation. The Embase, MEDLINE, and Cochrane databases were used (1980-2017). Random effects modeling was used to estimate effects on transplantation outcomes based on (1) aortic or dual in situ perfusion and (2) the use of University of Wisconsin (UW), histidine tryptophan ketoglutarate (HTK), Celsior, and/or Institut Georges Lopez-1 (IGL-1) solutions for perfusion/preservation. A total of 22 articles were included (2294 liver transplants). The quality of evidence ranged from very low to moderate Grading of Recommendations, Assessment, Development and Evaluations score. Meta-analyses were conducted for 14 eligible studies. Although there was no difference in the primary nonfunction (PNF) rate, a higher peak alanine aminotransferase (ALT) was recorded in dual compared with aortic-only UW-perfused livers (standardized mean difference, 0.24; 95% confidence interval, 0.01-0.47); a back-table portal venous flush was undertaken in the majority of aortic-only perfused livers. There were no relevant differences in peak enzymes, PNF, thrombotic graft loss, biliary complications, or 1-year graft survival in comparisons between dual-perfused livers using UW, HTK, Celsior, or IGL-1. In conclusion, there is no significant evidence that aortic-only perfusion of the DBD liver compromises transplantation outcomes, and it may be favored because of its simplicity. However, there is currently insufficient evidence to advocate for the use of any particular perfusion/preservation fluid over the others. Liver Transplantation 23 1615-1627 2017 AASLD.

Dual kidney transplant techniques: A systematic review.

BACKGROUND: Dual kidney transplantation (DKT) was developed to improve outcomes from transplantation of extended criteria donors (ECD). This study examined which surgical techniques have been reported for DKT and whether any technique had superior patient and graft survival. METHOD: Electronic databases were searched for published studies mapping to MESH terms: "kidney or renal" AND "transplan*" AND "dual or double." Single case reports, studies of patients less than 18 years old, studies which did not describe the surgical technique, and studies that did not report patient or graft survival were excluded. RESULTS: Fifteen reports of 434 DKT recipients were identified. Three techniques were described: bilateral placement; unilateral placement with separate anastomoses; and unilateral placement with patch anastomoses. Patient survival across all three techniques was over 95% at 1 year, and graft survival was also similar at over 90%. Rates of delayed graft function were between 20% and 30% across all techniques. CONCLUSION: The three techniques have equivalent delayed graft function as well as patient and graft survival rates. This is an encouraging result as it means that the surgeon can choose to use the technique which is most appropriate for their own skills and for the patient.

The Abdominal Reapproximation Anchor Device.

INTRODUCTION: Achieving primary fascial closure after damage control laparostomy can be challenging. A number of devices are in use, with none having yet emerged as best practice. In July 2013, at Westmead Hospital, we started using the abdominal reapproximation anchor (ABRA; Canica Design, Almonte, Ontario, Canada) device. We report on our experience. METHODS: A retrospective review of medical records for patients who had open abdomens managed with the ABRA device between July to December 2013 was done. Data extracted included age, sex, body mass index (BMI), reason for the open abdomen, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, number of laparostomies prior to ABRA placement, duration of placement, device complications, length of hospital and intensive care unit (ICU) stay, and outcomes. RESULTS: Four cases of open abdomens managed using the ABRA device were identified, with 3 a consequence of intra-abdominal sepsis and 1 a consequence of penetrating trauma. Mean BMI was 33.5 kg/m2, APACHE II score was 14.5, duration with open abdomen prior to ABRA placement was 11.75 days, duration with ABRA in situ was 9 days, duration of hospital stay was 64.25 days, and ICU stay was 37.75 days. Three patients (75%) achieved fascial closure, and 1 achieved skin closure. No incidences of enterocutaneous fistulae occurred. CONCLUSION: The ABRA is a unique emerging alternative to aid in achieving fascial closure in patients managed with open abdomens. Our case series demonstrates that it can be used effectively in selected patients. Studies are needed to compare its efficacy with more traditional methods.

A systematic review and meta-analysis of cold in situ perfusion and preservation for pancreas transplantation.

BACKGROUND: This study aimed to identify the most effective solution for in situ perfusion/preservation of the pancreas in donation after brain death donors, in addition to optimal in situ flush volume(s) and route(s) during pancreas procurement. METHODS: Embase, Medline and Cochrane databases were utilized (1980-2017). Articles comparing graft outcomes between two or more different perfusion/preservation fluids (University of Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK) and/or Celsior) were compared using random effects models where appropriate. RESULTS: Thirteen articles were included (939 transplants). Confidence in available evidence was low. A higher serum peak lipase (standardized mean difference 0.47, 95% CI 0.23-0.71, I2 = 0) was observed in pancreatic grafts perfused/preserved with HTK compared to UW, but there were no differences in one-month pancreas allograft survivals or early thrombotic graft loss rates. Similarly, there were no significant differences in the rates of graft pancreatitis, thrombosis and graft survival between UW and Celsior solutions, and between aortic-only and dual aorto-portal perfusion. CONCLUSION: UW cold perfusion may reduce peak serum lipase, but no quality evidence suggested UW cold perfusion improves graft survival and reduces thrombosis rates. Further research is needed to establish longer-term graft outcomes, the comparative efficacy of Celsior, and ideal perfusion volumes.

Outcomes of kidney paired donation transplants in relation to shipping and cold ischaemia time.

To assess the impact of shipping distance and cold ischaemia time (CIT) of shipped organs in a kidney paired donation (KPD) programme, we evaluated the outcomes of the initial 100 kidney transplants performed in the Australian KPD programme. In a 44-month period, 12 centres were involved in fifteen 2-way, twenty 3-way, one 4-way and one 6-way exchanges. Sixteen kidneys were transplanted at the same hospital (CIT 2.6 ± 0.6 h) and 84 required transport to the recipient hospital (CIT 6.8 ± 2.8 h). A spontaneous fall in serum creatinine by at least 10% within 24 h was observed in 85% of recipients, with no difference between nonshipped and shipped kidneys. There were two cases of transient delayed graft function requiring dialysis and patient and graft survival at 1 year were 99% and 97%, respectively. There was no difference in recipients of nonshipped compared with shipped kidneys with regard to serum creatinine at 1 month (mean difference (MD) 7.3 µmol/l, 95% CI -20.2 to 34.8, P = 0.59), 1-year graft survival (MD 3.9%, 95% CI -5.4 to 13.2, P = 0.41) or patient survival (MD -2.4%, 95% CI -10.0 to 5.2, P = 0.54). Despite prolonged CIT for interstate exchanges, the programme's decision to ship donor kidneys rather than the donor appears to be safe.

Percutaneous vs. endoscopic pre-operative biliary drainage in hilar cholangiocarcinoma - a systematic review and meta-analysis.

BACKGROUND: The strategy for preoperative management of biliary obstruction in hilar cholangiocarcinoma (HCCA) patients with regards to drainage by endoscopic (EBD) or percutaneous (PTBD) methods is not clearly defined. The aim of this study was to investigate the utility, complications and therapeutic efficacy of these methods in HCCA patients, with a secondary aim to assess the use of portal vein embolization (PVE) in patients undergoing drainage. METHODS: Studies incorporating HCCA patients undergoing biliary drainage prior to curative resection were included (EMBASE and Medline databases). Analyses included baseline drainage data, procedure-related complications and efficacy, post-operative parameters, and meta-analyses where applicable. RESULTS: Fifteen studies were included, with EBD performed in 536 patients (52%). Unilateral drainage of the future liver remnant was undertaken in 94% of patients. There was a trend towards higher procedure conversion (RR 7.36, p = 0.07) and cholangitis (RR 3.36, p = 0.15) rates in the EBD group. Where specified, 134 (30%) drained patients had PVE, in association with a major hepatectomy in 131 patients (98%). Post-operative hepatic failure occurred in 22 (11%) of EBD patients compared to 56 (13%) of PTBD patients, whilst median 1-year survival in these groups was 91% and 73%, respectively. DISCUSSION: The accepted practice is for most jaundiced HCCA patients to have preoperative drainage of the future liver remnant. EBD may be associated with more immediate procedure-related complications, although it is certainly not inferior compared to PTBD in the long term.

Renal transplantation: better fat than thin.

BACKGROUND: Obesity has been a relative contraindication for renal transplantation. This study evaluates the impact of pretransplant body mass index (BMI) on renal transplant outcomes in a single institution in the era of modern immunosuppression. MATERIALS AND METHODS: A 10-y retrospective analysis was undertaken of 454 consecutive patients who received a renal transplant at Westmead Hospital from January 1, 2001 to December 31, 2010. The role of pretransplant BMI on patient survival, graft survival, surgical complications, and postoperative complications was studied. RESULTS: The mean age of transplant of this study population was 45.4 ± 13.0 y. Live donation rate was 53.5%, and 60.6% were male. The median preoperative BMI was 25.6 (range, 14.3-51.4). One-year and 5-y patient survival were 97.4% and 86.6%, respectively, whereas 1-y and 5-y death-censored graft survival were 97.1% and 91.9%, respectively. Patients with BMI >30 did not exhibit any significant difference in survival or graft failure but had higher surgical wound infection rates (hazard ratio 3.95, P < 0.01). Patients with preoperative BMI <18.5 were associated with a six-fold increase in both death and death-censored graft failure (P < 0.01). CONCLUSIONS: Pretransplant obesity increases wound infection but is not a contraindication to renal transplantation. Future prospective studies are required to further define the impact of low preoperative BMI <18.5.