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

2. 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.

3. 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

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

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

6. 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

7. 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.

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

9. 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

10. 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

11. 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.

12. 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.

13. 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.

14. 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: /lt.25323

15. 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: /lt.25323

16. 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:

17. 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