Intestinal Transplant: Overview and Australian Perspective
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This document provides an overview of intestinal transplant (ITx) in Australia from 2009-2015, including: - ITx aims to fix "train-wrecks" or patients with irreversible intestinal failure and total parenteral nutrition failure. - The Australian ITx program was developed in 2009 building on liver transplant expertise, with the first transplant in 2010. - ITx involves transplanting isolated intestine, liver-intestine, or multivisceral organs, managed by a multidisciplinary team. - Barriers to ITx in Australia include donor shortage, funding challenges, high rates of sensitization, and referring complex late-stage patients. Possible solutions include establishing a national transplant authority and innovative de
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Intestinal Transplant: Overview and Australian Perspective
- 1. Intestinal Transplant: Overview & Australian Perspective (2009-2015) Dr Peter De Cruz
- 2. Intestinal Transplantation = Trying to Fix Train-Wrecks
- 3. If only fixing train-wrecks were easy…
- 4. The Magnitude of the Carnage pre-Tx…
- 5. The Patient Immediately Post-Tx …
- 6. Five Years Post-Tx – Train wreck Fixed
- 7. Intestinal Transplant Overview Who we transplant & who is involved? Which organs we transplant? What sort of service we provide? Barriers to intestinal transplant in Australia Possible solutions for the Future How & When to refer for transplant?
- 8. Who do we transplant & who is involved?
- 9. Who do we Transplant? Patients with TPN failure: • Impending/Overt liver failure due to TPN-induced liver injury • Thrombosis of two or more central veins (IJ,SC, SVC, IVC) • Two or more episodes/year of catheter related sepsis → hospital • Single episode of line-related fungaemia, septic shock, ARDS • Frequent episodes of severe dehydration despite IV fluids + TPN
- 10. Prerequisites for Intestinal Tx in Australia Irreversible intestinal failure + TPN Failure OR Complex abdominal visceral pathology (Desmoids)
- 11. Mortality in Intestinal Failure Pironi et al Gut 2011 30 % mortality in world’s best Intestinal Failure Centres Cause of death: < 2 years of TPN = Primary disease >2 years of TPN = Complications related to PN
- 12. Overall Actuarial Survival Post Intestinal Tx Grant et al Am J Trans 2015 Intestinal Transplant is indicated when anticipated 5 year survival is <57 %
- 15. History of Intestinal Transplantation • 1st human bowel transplant Boston 1964 (not reported) • 1st human multivisceral transplant (Starzl) in Pittsburgh, 1983 – 6yo girl: died immediately post-op from haemorrhage • Advent of tacrolimus 1989 • 1st “successful” (enteral autonomy) liver-intestinal Tx (Grant) 1990 • ~3000 ITx conducted since 1985 • 82 centres worldwide – Nth America accounts for 76% of world activity – ~40 active centres
- 16. Intestinal Transplant in Australia • Adult and Paediatric intestinal transplant (ITx) program developed in Australia in 2009 • Built upon success of Victorian Liver Transplant Unit Established in 1988 1000 liver transplants • Pre 2009 IF pts either died or sent overseas for ITx
- 17. Intestinal Transplant in Australia • New “hybrid” program built upon best-practice • Staff training and up-skilling at high-volume IF & ITx centres Surgeons: Pittsburgh USA, Birmingham UK Physicians: Pittsburgh, Birmingham, Cambridge, St Mark’s, Salford UK Dietitian: Pittsburgh USA Pathologist: Pittsburgh USA, Birmingham UK Nursing staff: Pittsburgh USA • Australia’s first ITx in July 2010 • Australia’s first combined ITx and Kidney transplant October 2015
- 18. Intestinal Rehabilitation: How do we achieve nutritional autonomy? A Multidisciplinary Approach is Essential • Photo from the Trout in Oxford
- 21. An Intestinal Transplant Program for Australia
- 22. Bowel obstruction Bilat hydronephrosis Recto sigmoid Multiple SB resection Constipation Large B obstruction PN Total laparotomies 17 Outpatient visits 120 / 2 yrs Pyeloplasty Laparotomy Colostomy Duodenal bypass SB resection jejunostomy Right nephrectomy 1979 Total colectomy J Pouch 1994 Cholecystectomy Infarction R liver AV fistula 19981977 2000 IFALD TX 2010 AV Fistula take down Australia’s 1st ITX - BC – 33yo male “Chronic Intestinal Pseudo-obstruction”
- 23. Pre Tx State BC PN related complications: •Recurrent line sepsis »multiple bacterial + candidal •Thromboses – Patent: SVC, IVC, RIJ, RSCV – Left saphenous vein thigh AV fistula – Venous obstruction left leg •IFALD
- 24. Pre Tx State BC • Residual gut 90 cm jejunum ? • Recurrent admissions – Dehydration – Stomal output 3 – 10 L • PN/IVT > 6 L / night • Q of L
- 25. Intestinal Failure Associated Liver Disease 0 50 100 150 200 250 300 10 20 30 40 50 Jun-07 Sep-07 Dec-07 Mar-08 Jun-08 Sep-08 Dec-08 Mar-09 Jun-09 Sep-09 Dec-09 Mar-10 Jun-10 Albumin Bilirubin g μm ol/ L
- 28. 50 cm
- 30. Pre-transplant • Unemployed • >120 hospital appointments in 2 years • TPN 14h/d • Pension for 17 yr • 17 laparotomies • Complications • Enteral autonomy • Off pension • Working full-time • Paying taxes • Living in rural Victoria Post-transplant
- 32. Which organs do we transplant?
- 33. Garg et al. J Gastroenterol Hepatol 2011 Isolated Intestine Tx Liver-Intestine Tx Multivisceral Tx (Intestine, Liver ± Stomach ± Pancreas ± Kidney)
- 34. What sort of service do we provide?
- 35. Austin & RCH Intestinal Transplant Program • Assessment of Suitability for Intestinal/Multivisceral Transplant • Advice regarding Intestinal Rehabilitation • Pre-Transplant Work-up • Intestinal/Multivisceral Transplant • Post-Transplant Management and Follow-up
- 36. Intestinal Rehab + Tx The Australian Experience (2009-2014) Chapman B et al Transpl Proceedings 2015 AIM •To analyse the outcomes of patients treated by our service over the past 5 years
- 37. Methods • Retrospective audit • Data collection: – Patient demographics – Underlying disease – Nutrition support – TPN complications – Transplant program status
- 38. Results: Demographics 60 PATIENTS 22 IF Aetiology: •SBS •Dysmotility IF Aetiology: •SBS •Dysmotility 38
- 43. Results: Current ITx Program Status
- 44. What are the barriers to Intestinal Transplant in Australia?
- 45. Barriers to ITx in Australia • Donor shortage – Median donor age 58 years • Funding arrangement/ “Tyranny of Distance” – Lack of consensus between State Governments – 56% of pt’s referred from interstate • High rate DSA – Highly HLA-sensitised – Increases waiting periods • Complex late-stage patients – High rate of co-morbid medical conditions
- 47. What are the possible solutions?
- 48. Possible Solutions • Establishment of Organ and Tissue Authority (2009) • Application for National Centre Funding • Innovative strategies to reduce antibody burden – Novel desensitization strategies • Program promotion & links with other Australian/NZ HPN centres & alignment of activity with AusPEN HPN registry • Development of ASIT – Australian Intestinal Transplant Forum • Link with ISIT – International Small Intestinal Transplant Forum
- 49. How & when to refer for Intestinal Transplant consideration?
- 50. When to refer for Intestinal Transplantation If in doubt …Ask • Irreversible Intestinal Failure (TPN dependent) +TPN failure = ≥ 1 of: • Impending/Overt Intestinal Failure Associated Liver Disease (IFALD) • Recurrent Catheter Related Blood Stream Infections (Line sepsis) • Central Venous Thrombosis (IJ, SC, SVC,IVC) • Complex abdominal pathology – Desmoid tumours
- 51. Referral Process Email: Adam.TESTRO@Austin.org.au Peter.DECRUZ@Austin.org.au Phone: 03 9496 5353 Fax : 03 9496 3487
- 52. Conclusion • ITx is now an available and life-saving option for patients with IF in Australia and NZ • Pt characteristics and indications for ITx in the Australian pt group are consistent with international literature • Early referral to specialist centre is imperative • Ongoing challenges to overcome
- 53. Acknowledgements Austin/RCH ITx Team • Adam Testro • Brooke Chapman • Kate Hamilton • Winita Hardikar • Bob Jones & Surgical Team • Julie Lokan & Path Team ITX Program Development • Darius Mirza • Geoff Bond AusPEN • Ibolya Nyulasi • Sharon Carey • Julie Bines • David Russell International Mentors/Collaborators • Simon Gabe, Mia Small, Alison Culkin • Steven Middleton • Jeremy Woodward • Kareem Abu-Elmagd, Laura Materese • Girish Gupte • Guilherme Costa • Kishore Iyer
- 54. “The history of medicine is that what was inconceivable yesterday, and barely achievable today, often becomes routine tomorrow.” Thomas E. Starzl
- 55. The Future of Intestinal Transplant in Australia
Editor's Notes
- Word’s best centers for IF approx 30% mortality rate
- Graft and pt survival rates have improved significantly over time. For pt transplanted in the era since 2000, actuarial pt survival is now 77% at 1 year, 58% at 5 years, and 48% at 10 years. The reasons for graft loss and pt death have not changed over time. Sepsis remains the leading cause accounting for over 50% of cases, followed by rejection (13%) and cardiovascular events (8%).
- A joint adult and paediatric ITx program for Australia was developed in 2009. The program was established between Austin Health and the Royal Children’s Hospital in Melbourne, and built upon the success of the Victorian LTU, where a collaborative partnership between the adult and children’s hospitals has been in place since 1988. Prior to 2009 pt’s with IIF either died from complications of their disease, or a couple of pt’s sent overseas for ITx at significant cost to Federal Govt (&gt;$7M)
- The new ITx program has been developed based upon best-practice models and established protocols. Between 2007-2011, a variety of staff from our unit have travelled overseas to high-volume ITx centres, for upskilling and training. Culminated in performing Australia’s first ITx in July 2010.
- How do we achieve nutritional autonomy?
- Transplantation reserved for patients with cx of TPN and complex abdominal visecral path
- Uo front transplant over HPN with More patients being transplanted for QOL reasons rather than complications of TPN
- The solution is intestinal transplantation. A process where the damaged intestine is removed and replaced with a donor intestine…but this is easier said than done.
- 3 types of ITx surgery are available: Isolated intestine (45% of all Tx conducted) Combined liver-intestine (31%) Multivisceral (intestine, liver, ± stomach/pancreas/kidney) (23%)
- A retrospective medical record review was conducted on al patients with IF referred to our service since it’s inception. Patient characteristics at the time of assessment by our service, aetiology of IF, type of nutrition support, presence of PN complications, patient outcome and current transplant program status at the end of the study period (Dec 2014) were recorded.
- A total of 60 patients throughout Australia and New Zealand have been referred to the program. 38 adults, with a mean age of 39.3 years, and 22 paediatric patients, mean age 6.3 years. Leading cause of IF aetiology was SBS in over 50% of adult and paed pt’s, followed by motility disorders.
- Patients were referred to the intestinal transplant program from almost all states and territories across Australia, with the majority coming from the Eastern seaboard (Victoria, New South Wales, Queensland) and New Zealand.
- The majority of patients were reliant on TPN as their sole source of nutrition at the time of referral to the program with this proportion higher in paediatric (77%) versus adult (53%) patients, though a modest number were able to consume some oral/enteral nutrition in conjunction with TPN (18% and 24% of paediatric and adult patients, respectively), or required intravenous fluid support in addition to oral/enteral nutrition (5% paeds, 23% adult pt’s).
- The prevalence of liver failure, recurrent sepsis, and impending loss of venous access in adult and paediatric patients upon referral to the transplant program can be seen in the graph. 70% of patients (n=40) presented with at least 1 of the 3 well-recognised life-threatening complications of TPN And although not represented in this graph, many patients presented with multiple complications
- One third (n=19) of all referred pt were suitable for listing for intestine, liver-intestine, or multivisceral transplant. Four patients (2 adults, 2 children) have undergone ITx with 100% survival and all have achieved nutritional autonomy. 3 patients received liver-intestine grafts, 1 patient isolated intestine. Five patients (4 adults, 1 child) are currently wait-listed for transplant, with w/list time ranging from 30 -1825 days An additional 6 patients (all interstate) have current indications for ITx, but are awaiting formal assessment for transplant for reasons I will explain shortly, and 4 adult patients have died (2 while awaiting transplantation, 2 during assessment period). Causes of death included sepsis and intracranial bleed.
- Two-thirds of all referred patients (n=41) have been deferred or rejected from wait listing for various reasons Of the pts that were assessed, but not listed, the most common reason for not listing was not meeting tx criteria (either ‘stable’ disease or stable on TPN); A small proportion of pt’s were too unwell for tx and rejected due to medical contraindication/other severe co-morbidities and one adult pt has been unsuitable for psychosocial reasons
- Although the early results in terms of patient and graft survival here is promising, the barriers to ITx in Australia need to be highlighted as to why only 3 Tx have been carried out in the 5 years, and why time to Tx is so long for those on the waiting list. Australia has long had notoriously poor organ donation rates despite excellent outcomes for solid organ transplant. Prior to 2009, the donor rate remained under 11 dpmp, less than half that of the UK, USA and Europe. The median donor age in Aust is also 58 years, and typically suitable bowel come from donors under the age of 40. The number of patients awaiting formal intestinal transplant assessment and subsequent listing relates to the fact there is no Federal funding stream for the intestinal transplant program. As such, the Victorian state government covers costs for Victorian patients, but for those living outside of Victoria (56% of those referred), a funding agreement needs to be reached on a case-by-case basis. A high rate of donor specific antibodies also exist in our pt on the bowel Tx W/L. These pt’s are highly HLA-sensitised, and an appropriate HLA-match is now thought to be a key factor in determining successful ITx outcome. Sick, complex pt are inherent in this field however those referred late with multiple PN complications and co-morbidities add another layer of complexity when allocating donor organs.
- Single greatest predictor of outcome is antibody status. By Matching the right recipient with right graft allows us to achieve 10 year survival of 80% which rivals all other solid organs . If un unfavourable antibody match there is a rapid an progressive risk of graft loss up to 50% at 2 years. The reason for patients waiting so long is that we endeavour to match donor to recipient as best we can © This slide is made available for non-commercial use only. Please note that permission may be required for re-use of images in which the copyright is owned by a third party. Cumulative conditional visceral allograft survival according to the donor specific antibody (DSA) status (A) before and (B) after transplantation.
- Some possible solutions to these challenges include: The establishment of the Organ and Tissue Authority in Australia in 2009, which set about reforming organ and tissue donation in this country. By 2014, the donor rate had increased by over 40% to 16.1 dpmp, and bridging the gap between Australia and countries such as the UK (20.8 dpmp) and USA (25.9 dpmp), but remains about half that of European world leaders such as Spain and Croatia (35 dpmp) Achieving Federal Government funding is a priority for the program, to ensure future patients are not delayed in their attempts to be properly assessed and listed when referred for life-saving intestinal transplant. Innovative strategies to reduce antibody burden such as plasmapharesis are currently being employed in our highly-HLA sensitised patients And promotion of the program in forums such as this and in fostering links with other HPN centres is also paramount.
- After 5 years of establishing the first dedicated ITx program in Australia and NZ, early results indicate that ITx is an available and life-saving option for IF patients in these countries. Patient characteristics and indications for ITx in our patient group are consistent with those reported in the international literature. Due to long wait list times and organ shortage, the precise identification of eligible patients and early referral to a specialist centre is imperative. Unfortunately, a significant number of challenges remain and these issues need to be addressed. Working with stakeholders to overcome these issues, as well as increasing awareness and optimizing IF management will aid in improving both patient and program outcomes.
- After 5 years of establishing the first dedicated ITx program in Australia and NZ, early results indicate that ITx is an available and life-saving option for IF patients in these countries. Patient characteristics and indications for ITx in our patient group are consistent with those reported in the international literature. Due to long wait list times and organ shortage, the precise identification of eligible patients and early referral to a specialist centre is imperative. Unfortunately, a significant number of challenges remain and these issues need to be addressed. Working with stakeholders to overcome these issues, as well as increasing awareness and optimizing IF management will aid in improving both patient and program outcomes.
- After 5 years of establishing the first dedicated ITx program in Australia and NZ, early results indicate that ITx is an available and life-saving option for IF patients in these countries. Patient characteristics and indications for ITx in our patient group are consistent with those reported in the international literature. Due to long wait list times and organ shortage, the precise identification of eligible patients and early referral to a specialist centre is imperative. Unfortunately, a significant number of challenges remain and these issues need to be addressed. Working with stakeholders to overcome these issues, as well as increasing awareness and optimizing IF management will aid in improving both patient and program outcomes.