ESOT Consensus Platform for Organ Transplantation: Setting the Stage for a Rigorous, Regularly Updated Development Process

The European Society for Organ Transplantation (ESOT) has created a platform for the development of rigorous and regularly updated evidence based guidelines for clinical practice in the transplantation field. A dedicated Guideline Taskforce, including ESOT-council members, a representative from the Centre for Evidence in Transplantation, editors of the journal Transplant International has developed transparent procedures to guide the development of guidelines, recommendations, and consensus statements. During ESOT’s first Consensus Conference in November 2022, leading experts will present in-depth evidence based reviews of nine themes and will propose recommendations aimed at reaching a consensus after public discussion and assessment by an independent jury. All recommendations and consensus statements produced for the nine selected topics will be published including the entire evidence-based consensus-finding process. An extensive literature review of each topic was conducted to provide final evidence and/or expert opinion.


Appendix 1 Preliminary list of PICO questions
Topic: Machine perfusion in cardiothoracic transplantation 1. In heart transplantation, for which heart should machine perfusion be performed? 2. In heart transplantation which protocol/perfusate/perfusion strategy for ex-vivo/ex-situ heart perfusion leads to: • the highest conversion rates to transplantation?
• PGD-rate distribution after transplantation • the lowest rate of postoperative graft failure?
• the best 30-day survival/90-day survival and 1 year survival 3. In heart transplantation, which biomarker / parameter is capable to predict the graft survival, graft function, primary non function(O) during ex vivo Heart perfusion? 4. In heart transplantation, which recipients should benefit from a heart assessed by machine perfusion: 1. For the evaluation of chronic lesions in ECD kidneys, is the needle core biopsy comparable/inferior/superior to wedge biopsy or punch biopsies (with a skin puncher as in PMID 22492825) in terms of representativity of the entire renal parenchyma? 2. For the evaluation of chronic lesions in ECD kidneys, is the frozen section comparable/inferior/ superior to paraffin embedded section in terms of reliability of the reading from pathologists? 3. For score assessment of pre-implantation kidney biopsy in the evaluation of ECD is the experienced renal pathologist comparable/inferior/superior to on-call pathologist in terms of reproducibility and accuracy of the histological report? 4. In the quantification of the chronic damage in ECD kidneys, is glomerulosclerosis more reproducible in comparison with other parameters (interstitial fibrosis, tubular atrophy, wall/lumen ratio, arteriolar hyalinosis)? 5. In the quantification of the chronic damage in ECD kidneys is measurement of histological variables with digital pathology comparable/inferior/superior if compared with light microscopy? 6. In the quantification of the chronic damage in ECD kidneys is measurement of histological variables with the aid of special stainings (PAS/Trichromic/Silver) comparable/inferior/superior if compared with H&Eosin alone? 7. For ECD is the histological assessment comparable/inferior/superior to demographics and clinical variables (e.g. KDPI, GFR) to predict graft survival, graft function, primary non-function? 8. In the quantification of the chronic damage in ECD kidneys, is glomerulosclerosis percentage more representative than other parameters (interstitial fibrosis, tubular atrophy, arteriolar hyalinosis and cv score) to predict the graft survival, graft function, primary non-function? 9. In the quantification of the chronic damage in ECD kidneys, are histological composite scores (e.g.Karpinski-Remuzzi, CADI score,..) more representative than single parameters (glomerulosclerosis, interstitial fibrosis, tubular atrophy, arteriolar narrowing, arteriosclerosis) to predict the graft survival, graft function, primary non function? 10. In the quantification of the chronic damage in ECD kidneys, is a combined clinicalhistopathological score more representative than histological score alone to predict the graft survival, graft function, primary non function? (emergence of MDR bacteria) 2. When should PSC patients on the waiting list be treated with biliary stents? 3. Can we identify parameters that support the decision-making process of liver retransplantation for PSC recurrence? 4. Can we develop a strategy to monitor PSC recipient of LT for disease recurrence? 5. Is pre-emptive LT indicated for high-grade dysplasia in suspicious strictures? 6. Is the MELD allocation system suitable for patients with PSC? 7. Optimal immunosuppression for patients transplanted with PSC: • What endpoints should be used?
• What combinations are used mainly?
• Impact of steroids • Monotherapy or combination therapy • Impact of age, possibly pregnancy, IBD, type and extent of IBD 8. In liver transplantation for PSC: duct-to-duct anastomosis vs to Roux-en-Y hepaticojejunostomy 9. Is the use of ECD (including DCD) in PSC associated with higher rate of NAS compared to other LT indications? 10. What are the best screening and surveillance strategies for IBD associated with PSC?
(Screening for the presence of IBD, monitoring activity of IBD, bowel cancer surveillance in IBD in pre-, peri-and post-LT).
11. What is the optimum therapeutic approach for maintaining remission in IBD associated with PSC; pre-, peri-and post-transplant? (Safety and efficacy profiles of biologics, calcineurin inhibitors, anti-proliferatives and corticosteroids) 12. Colectomy in PSC-associated colitis: indications, timing and type, and the impact on liver-related outcomes.
• When the colectomy is indicated?
• What is the optimal timing for colectomy with regards native liver-related, graftrelated, and overall survival? • How does the timing of colectomy (pre-, peri-or post-transplant) affect the incidence and risk of developing recurrent PSC and/or other graft-related complications? • What is the optimal timing for colectomy (pre-, peri-or post-transplant) with regards minimising peri-operative (peri-transplant) complications? • Does the type of colonic resection (i.e. restorative vs. non-restorative colectomy; ileal pouch anal anastomosis vs. ileorectal anastomosis vs. ileostomy alone) affect the outcomes listed in 1-3 above? • How does the timing of colectomy (pre-, peri-or post-transplant) affect perioperative outcomes with regards the colonic resection procedure itself?
Topic: Clinical Endpoints in liver transplantation according to value-based care 1. Which is the best single measure to evaluate liver transplantation process as a whole from the VBC perspective? 2. In Liver transplant recipients which is the best tool to adjust for quality of life the life gain of liver transplantation? 3. When gain in life years or reduction in years lost are not available/calculable which is the best measure to describe the transplant process from a VBM perspective? 4. What is the most appropriate time frame to assess liver transplant outcomes from a VBM perspective? 5. In a setting with optimal potential candidate referral and listing process, which is a the best measure to evaluate the quality of waiting list management in a VBHM perspective? 6. Which is the best metrics to describe the quality of early postoperative course? 7. Which are the unmet needs in defining the critical PROMs and PREMs to be included in liver transplant "core" evaluation and clinical trial design?
Topic: Downstaging, bridging and immunotherapy in liver transplantation for HCC