A Year in Review: Small Bowel/Intestine Maria H. Alonso, MD Pediatric and Transplant Surgeon Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio

A Year in Review: Small Bowel/Intestine Clinical condition characterized by inability of the GI tract to maintain adequate nutrition, fluid/electrolyte balance, or normal growth and development Dependence on parenteral nutrition Acute or chronic loss of enteric mass – failure of small bowel adaptation to meet functional demands Intestinal dysmotility, enterocyte dysfunction Intestinal failure results from the inability to maintain adequate nutrition, fluid and electrolyte balance resulting in impaired growth and development. The result is a dependence on TPN.

A Year in Review: Small Bowel/Intestine Multidisciplinary approach has improved outcomes Alternative lipid management alternate lipid emulsions(omegaven, SMOF) lipid lowering strategies Surgical interventions(LILT and STEP) Use of ethanol locks- fewer BSI’s and hospitalizations, fewer catheter replacements Use of GLP-2 analogs to promote physiologic adaptation

A Year In Review: Small Bowel/Intestine Surgical Options Longitudinal intestinal lengthening procedure(LILT), Bianchi procedure

A Year In Review: Small Bowel/Intestine Surgical Options Serial Transverse Enteroplasty (STEP)

A Year in Review: Small Bowel/Intestine Potential Benefits of LILT or STEP Recovery to normal liver function Stabilization of liver disease as a bridge to transplant Reduction of bacterial overgrowth and translocation Reduction in bowel related central line infections and sepsis

A Year in Review: Small Bowel/Intestine Although most children with intestinal failure can be successfully rehabilitated, a small proportion are refractory to standard medical and surgical strategies and this is where intestinal transplantation plays a role.

A Year in Review: Small Bowel/Intestine OPTN Data: Intestinal Transplants in the Pediatric Population

A Year in Review: Small Bowel/Intestine Choice of graft Isolated intestinal graft Modified multivisceral graft Improved pre transplant IF care, earlier referral-increase candidates for IITx Liver–inclusion intestinal graft Still required most often in infants Consideration for re transplant patients Severity of IFALD Multivisceral graft Inclusion of colon- increased from 4% to 30% of intestinal grafts over last decade Improved stool quality No impact on patient or graft survival

A Year in Review: Small Bowel/Intestine Assessment of IFALD Liver inclusive Hyperbilirubinemia Stage 3(bridging) or 4(cirrhosis) fibrosis Synthetic dysfunction Portal hypertension Isolated intestine Early fibrosis No stigmata of portal hypertension Mild hyperbilirubinemia

A Year in Review: Small Bowel/Intestine Intestinal re transplantation Single center review 18 re transplants Rejection most common indication ATG and Rituximab induction, tacrolimus maintenance and methylprednisolone premeds tapered over 3-6 months 7 patients had graftectomy before re transplant 13/15 patients received liver inclusive grafts Immunologic Technical Ekser, B. et al. Clinical Transplantation. 2018;32:e13290.

A Year in Review: Small Bowel/Intestine Intestinal re transplantation DSA data available for 13/18 patients-2 developed DSA with 1 survivor Average time to re transplant was 616 days(median 421) 6 transplants were performed within 90 days with 80% survival Late re transplants had 50% survival Patient and graft survival curves mirrored those for primary transplant outcomes Ekser, B. et al. Clinical Transplantation. 2018;32:e13290.

A Year in Review: Small Bowel/Intestine Expanded indication? Case series of 4 children with MVT from intra abdominal tumors with extensive involvement of visceral arteries or porto mesenteric venous system Tumors were HCC(1), HB(2) and IMT(1) All had ATG induction with tacrolimus for maintenance All children have good allograft function and are alive without evidence of disease at 3-8 years post transplant Lee, E. Pediatric Transplantation. 2017;21:e12904.

A Year in Review: Small Bowel/Intestine Antibody mediated rejection with a pediatric focus 43 pediatric intestinal transplants(mean age at transplant 5.3 y, 3.7 y f/u, 33 were liver inclusive) Only re transplant patients(11.6%) had preformed DSA, all had peritransplant desensitization with IVIg, then plasmapheresis and rituximab if presence of DSA persisted 2 cleared antibodies with treatment Preformed DSA did not emerge as risk factor for rejection or survival but pts had higher frequency of PTLD Talayero, P. doi: 10.1002/lt.25323

A Year in Review: Small Bowel/Intestine Antibody mediated rejection with a pediatric focus 7 developed de novo DSA, 5 with MFI >10,000 which correlated with positive C1q binding assay dnDSA was independent risk factor for graft loss dnDSA mostly directed against HLA-class II Liver inclusion emerged as protective factor (7% vs 50%) Higher survival of liver inclusive grafts at 5 years Talayero, P. doi: 10.1002/lt.25323

A Year in Review: Small Bowel/Intestine Identification of histopathologic features associated with C4d positivity in pediatric patients 23 patients, mean age 6.6 y 78% developed DSA with >1,000 MFI, 6 of these had preformed DSA dnDSA was identified within 2 weeks of transplant 50% of the 18 had C1q-fixing DSA, mainly Class II Identified capillaritis as major determinant of C4d+, lamina propria inflammation, mucosal erosion/ulceration and chorion edema also associated with C4d+ These may be criteria of ABMR in intestinal transplants Rabant, M. Am J Transplant. 2018;18:2250-2260.

A Year in Review: Small Bowel/Intestine Summary US graft survival rates for isolated intestine are 80% at 1 year, 70% for Liver-intestine and multivisceral Worldwide current actuarial survival rates for intestinal transplantation are 76%, 56% and 43% at 1,5 and 10 years Rates of graft loss beyond 1 year have not improved Clearly more work to be done