Difficult decisions: Intes0nal Transplant

Transcription

1 Difficult decisions: Intes0nal Transplant Dr Lisa Sharkey, Consultant Physician Cambridge Intes;nal and Mul;visceral Transplant team

2 Types of intes;nal containing graas Intes&ne only (SB) Mul&visceral Transplant (MVT) Modified Mul&visceral Transplant (MMVT)

3 Global number of ITx = 3414 Adults / children: 49% / 51% Isolated Combined Multivisceral Bowel Liver + Bowel 45% 31% 24% Data from the International Transplant Registry presented at the 3 CIRTA 2017, New York, USA

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5 Figure 2.4 Total number of intestine transplants, 1 April March 2017 No. of transplants Source: Source: Annual Annual Report Report on for Intestine Intestinal Transplantation Transplantation 2016/17, 2016/17, NHS NHS Blood Blood and and Transplant Transplant / / / / / / / / / /2017 Financial Year

6 Transplanting the bowel is crazy: It is like transplanting a huge lymph node Ischemia Reperfusion Injury (IRI) enwrapped in faeces Rejection David Sachs Graft-v-Host Disease (GvHD)

7 UK Criteria for Intes/nal Transplant NHSBT Pa/ent Selec/on Policy Sept Irreversible Intes&nal Failure, plus a. Progressive IFALD (Liver or non-liver containing grah depending on severity of disease) b. Severe sepsis (>1 life-threatening CRBSI for which no remedial cause can be found, or endocardi&s or other metasta&c infec&on) c. Limited central venous access (Venous access limited to 3 major conven&onal sites) d. Very poor QoL thought to be correctable by transplanta&on 2. Need for extensive eviscera&on, considered untenable without associated transplant 3. Requirement for transplanta&on of another organ where exclusion of simultaneous intes&nal transplant would adversely affect survival

8 Emerging Indica;ons Widespread splanchnic ischaemia (simultaneous or sequen&al occlusion of Coeliac Axis and SMA) *

9 Non Cirrho&c Portal Hypertension with recurrent Life-threatening bleeding All other op&ons exhausted first (TIPSS, surgical shunt, splenectomy, gastric devascularisa&on) Pa&ents requiring a Whipple s procedure with concurrent extensive portomesenteric venous thrombosis Al St st l ri Ma w ore ght rk re het d i s r s H co he n es o rd r e an er sp in le in ve ita g or ctro form d. N l, H an ni a o ar y c, tio pa row ot m n rt he ec re o, L r m ha trie f th on ed nic va is p don iu al, l sy ub, U m p s li K w ho tem ca. ith to ti ou co or on t t py tra ma he in n y w g, I sm be rit nt itt re te er ed p n n r co et by od ns pu an uc en bl y ed t o ica oth, f t tio er he n, m ea pu ns bl is, he r. Emerging Indica;ons

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12 Indica;ons at CUH

13 Standard assessment pathway Preliminary Discussion: Adequacy of imaging Discussion of options Agreement on investigations Invite for assessment 2 week assessment: Cardiovascular Respiratory Radiology Anaesthetic review Hepatology Nutrition Psychiatry Haematology Pathology Chronic pain Extensive discussions re consent Discussion at local MDT: Multi-visceral Liver Renal NASIT Lis&ng

14 The Transplant: Eviscerated abdomen Clamp on Hepa&c veins Stapled off oesophagus Arterial Conduit (donor thoracic aorta)

15 Reperfusion

16 Surgical problems Time And Space

17 Immunosuppression Induc&on Lymphocyte deple&on (Campath / Alemtuzumab, an&-cd52) 1-2 doses + Methylprednisolone 500mg Maintenance Tacrolimus (trough level 8-12) Methylprednisolone 20mg BD for first week, then taper An&metabolite from 4 weeks An&bio&c/An&fungal/CMV and PCP prophylaxis

18 Post-Transplant Complica/ons Not unique to Intes&nal or MVT but higher rates? Acute cellular rejec&on Atypical (and typical!) infec&ons GraH-versus-host-disease Coagulopathy +/- thrombo&c tendencies Drug-induced leucopenia Posterior Reversible Encephalopathy Syndrome Post-transplant TTP Renal Failure CMV Encephalopathy iatrogenic Portosystemic shunt, encephalopathy of acute rejec&on

19 Post-Transplant Complica/ons Acute cellular rejec0on Atypical (and typical!) infec0ons GraE-versus-host-disease Coagulopathy +/- thrombo&c tendencies Drug-induced leucopenia Posterior Reversible Encephalopathy Syndrome Post-transplant TTP Renal Failure CMV Encephalopathy iatrogenic Portosystemic shunt, encephalopathy of acute rejec&on

20 Graft Rejection 30-40% our pa&ents experience an episode of acute cellular rejec&on (ACR) in the first year Presenta&on: Asymptoma&c High output stoma, abdominal pain, fever Severe sepsis (secondary to transloca&on) Diagnosis: GraH endoscopy & biopsy epithelial apoptosis CT, US Biomarkers?

21 MILD Al St st l ri Ma w ore ght rk re het d i s r s H co he n es o rd r e an er sp in le in ve ita g or ctro form d. N l, H an ni a o ar y c, tio pa row ot m n rt he ec re o, L r m ha trie f th on ed nic va is p don iu al, l sy ub, U m p s li K w ho tem ca. ith to ti ou co or on t t py tra ma he in n y w g, I sm be rit nt itt re te er ed p n n r co et by od ns pu an uc en bl y ed t o ica oth, f t tio er he n, m ea pu ns bl is, he r. Endoscopic appearances of rejection SEVERE EXFOLIATIVE

22 Recovery from rejection

23 Increase immunosuppression Decrease/stop immunosuppression Novel therapies 10% incidence post ITx Presenta&on Rash (biopsy-interface derma&&s, FISH) Other sites na&ve GI tract, liver, lungs, eyes, kidney, bone marrow Peripheral T cell chimerism Management op&ons Al St st l ri Ma w ore ght rk re het d i s r s H co he n es o rd r e an er sp in le in ve ita g or ctro form d. N l, H an ni a o ar y c, tio pa row ot m n rt he ec re o, L r m ha trie f th on ed nic va is p don iu al, l sy ub, U m p s li K w ho tem ca. ith to ti ou co or on t t py tra ma he in n y w g, I sm be rit nt itt re te er ed p n n r co et by od ns pu an uc en bl y ed t o ica oth, f t tio er he n, m ea pu ns bl is, he r. Graft versus Host Disease

24 (EBV-driven) PTLD 10% Treatment: Reduce IS Rituximab

25 Renal Dysfunction post ITx More common than any other SOT Strategies to improve inclusion of colon, restoring con&nuity, hyperhydra&on, switch CNI to sirolimus Ojo et al. N Engl J Med 2011

26 Infec&ons Increasing problem with ESBL, VRE, CRE Candida and aspergillus most common fungal infec&ons Presence of microbiologists and infec&ous diseases teams at MDT crucial

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28 Most common viral infec&on Overall rate has fallen with matching GCV-resistant cases problema&c Al St st l ri Ma w ore ght rk re het d i s r s H co he n es o rd r e an er sp in le in ve ita g or ctro form d. N l, H an ni a o ar y c, tio pa row ot m n rt he ec re o, L r m ha trie f th on ed nic va is p don iu al, l sy ub, U m p s li K w ho tem ca. ith to ti ou co or on t t py tra ma he in n y w g, I sm be rit nt itt re te er ed p n n r co et by od ns pu an uc en bl y ed t o ica oth, f t tio er he n, m ea pu ns bl is, he r. Cytomegalovirus (CMV)

29 Nutri;onal outcomes

30 Patient three-year survival, including super urgent patients, following first intestinal transplant, by ITR group, for patients transplanted between 1 January 2006 and 31 March 2016 at Cambridge transplant unit

31 Intes;nal Transplant in 2017 Outcomes for Intes&ne-only grahs remain beper than liver containing grahs Esp important in IF pa&ents (watch the liver!) Indica&ons are expanding but other op&ons should s&ll be explored first Timely referral is key (but can be difficult!) Developing strategies for managing complica&ons We are happy to discuss any case

32 Transplant Physicians Dr Stephen Middleton Dr Jeremy Woodward Dr Dunecan Massey Dr Lisa Sharkey Transplant Surgeons Mr Andrew Butler Mr Neil Russell Mr Neville Jamieson Mr Paul Gibbs Prof Chris Watson Co-ordinators Jackie Green Samantha Duncan Louise Woolner Diane Bond Acknowledgements CUH Medical Staff Miss Irum Amin Dr Sara Upponi Dr Ed Godfrey Dr Effrosyni Gkrania-Klostas Dr David Enoch Dr Will Gelson Dr Jo Leithead All fellows past and present Our pa/ents and their families!

33 Fellowships available! Star&ng March or September each year 6 months or 1 year Intes&nal Failure and Transplant experience lisa.sharkey@addenbrookes.nhs.uk if you are interested