1. Intestinal transplantation
Dr. Richard S. Mangus, MD MS FACS
Assistant Professor of Surgery
Contact: rmangus@iupui.edu
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2. Intestinal Failure
Definition and Etiologies
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3. Intestinal Failure - Definition
• Failure of digestion and absorption
• Inability of the intestinal tract to maintain adequate
nutritional status and fluid / electrolyte balance
• Results from a loss or absence of sufficient
functional intestinal area
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4. Intestinal Failure - Etiology
Children
• Short gut (necrotizing enterocolitis, others)
• Intestinal atresia
• Midgut volvulus
• Gastroschisis
• Hirschprung’s disease
• Microvillus inclusion disease
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5. Intestinal Failure - Etiology
Adults
• Short gut
• Mesenteric thrombosis (arterial or venous)
• Trauma
• Inflammatory bowel disease / Crohn’s
disease
• Pseudo-obstruction
• Tumors (desmoid, neuroendocrine tumors)
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6. Intestinal Failure
Management issues
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7. Intestinal Failure - Management
• Medically or surgically alter the remaining
intestine to compensate for inadequate
absorptive surface area
• Meet caloric and nutritional requirements via
an alternate route (parenteral nutrition (PN))
• Intestinal transplantation
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8. Parenteral nutrition (PN)
• First line therapy
• Requires long term central venous access
• Labor intensive
• Expensive (total costs up to $1000/day)
• Associated with serious and frequent
complications
– Infections
– Loss of vascular access
– Electrolyte abnormalities
– Nutritional deficiencies (trace metals, other)
– Liver disease
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9. Parenteral nutrition – complications
• Catheter related sepsis:
– Standard site infection
– Seeding from compromised intestine
• Bacterial translocation
• Avoiding catheter infections
– Meticulous site care
– 70% alcohol dwell
– Antibiotic dwell
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10. Parenteral nutrition – complications
• Loss of vascular access
– 6 primary sites for vascular access
• Jugular, subclavian, femoral
– Thrombus formation
• May require anticoagulation
• Heparin dwell
– Vein sclerosis / narrowing
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11. Parenteral nutrition – complications
• Cholestatic liver disease
– Progressive cholestasis and cirrhosis
– Rate of progression may be associated with
length of remaining intestine
• Full intestinal length – liver failure slow onset
• Short intestinal length – more rapid
progression
– Low lipid strategies
• <1g/kg per day
• Every other day or 3x/week lipids
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12. Parenteral nutrition – complications
• Cholestatic liver disease (continued)
– Liver function tests in short gut patients are
altered after 6 months in 15% to 40% of
adults and 95% of children
– Chronic cholestasis related to short gut,
bacterial overgrowth, lipid infusion > 1g/kg,
overfeeding , lack of oral feedings, infections
– Liver dysfunction is the ultimate cause of
death in 30 to 40% of PN patients
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13. Parenteral nutrition – FAILURE
• Medicare approved criteria for PN failure:
– Impending/overt liver failure due to PN-induced liver
injury
– Thrombosis of 2 or more central venous access sites
– The development of 2 or more episodes of systemic
sepsis secondary to line infection, in one year, that
requires hospitalization indicates failure of PN therapy
– A single episode of line-related fungemia, septic shock,
and/or acute respiratory distress syndrome is
considered an indicator of TPN failure
– Frequent episodes of severe dehydration despite
intravenous fluid supplementation in addition to TPN.
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14. Intestinal Transplantion
Transplant options
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15. Intestinal transplantation
• Advantages:
– Replace normal intestinal anatomy, continuity
– Patient able to eat and drink
– Chance for definitive cure of disease
– Able to stop PN
• Remove central venous catheters
– Decrease infection risk
– Decrease risk of loss of vascular access
• Reversal of liver injury
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16. Intestinal transplantation
• Disadvantages:
– Risks of major surgery
– Risk of rejection
– Risks of life-long immunosuppression
• Infections
• Cancers
• Renal failure
• Graft versus host disease
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17. Intestinal Transplantation - surgery
• Intestinal transplant options:
– Isolated intestinal transplant
• Small intestine only
– Modified multivisceral transplant
• Small intestine + pancreas + stomach
– Full multivisceral transplant
• Small intestine + pancreas + stomach + liver
– Can add in other organs, as indicated
• +/- kidney
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18. Intestinal Transplantation - surgery
• Surgical considerations:
– Organs to include
– Composite or separate
– Whole or reduced size
– Arterial inflow
– Venous outflow
– Enteric connection
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19. Intestinal Transplantation
• Intestinal transplant : Recipient
operation
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20. Intestinal Transplantation
• Isolated intestinal transplant
– Indication: Intestinal failure in the absence of
any other organ failure
• Normal function of liver, stomach, pancreas
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21. Intestinal Transplantation
• Isolated intestinal
transplant
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22. Intestinal Transplantation
• Isolated intestinal
transplant
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23. Intestinal Transplantation
• Isolated intestinal
transplant
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24. Intestinal Transplantation
• Modified multivisceral transplant
– Indication: Intestinal failure in the absence of
liver failure
• Normal function of liver
• Dysfunction of stomach, intestine, +/- pancreas
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25. Intestinal Transplantation
• Modified
multivisceral
transplant
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26. Intestinal Transplantation
• Modified multivisceral transplant
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27. Intestinal Transplantation
• Multivisceral transplant
– Indication: Intestinal failure with liver failure
• Dysfunction of liver and intestine
• +/- dysfunction of stomach and pancreas
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28. Intestinal Transplantation
• Multivisceral
transplant
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29. Intestinal Transplantation
• Multivisceral transplant:
– Liver / intestine
transplant (+/- pancreas)
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30. Intestinal Transplantation
• Multivisceral
transplant
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31. Intestinal Transplantation
• Multivisceral
transplant
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32. Intestinal Transplantation
• Multivisceral
transplant
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33. Intestinal Transplantation
• Non-traditional indications:
– Diffuse mesenteric thrombosis
– Benign/ low grade malignant tumors involving the
mesenteric root
• Neuroendocrine tumors (carcinoid, insulinoma, others)
• Desmoid tumors
– Abdominal catastrophes / fistulas
– Radiation enteritis
– Trauma
– Enteropathies / dysmotility disorders
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34. Post-transplant care
Complications
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35. Intestinal Transplantation - Rejection
• Rejection
– Isolated and modified multivisceral (liver
excluded)
• 1-year risk of rejection 45-50%
– Multivisceral (liver included)
• 1-year risk of rejection 15%
• Liver known to be protective against rejection
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36. Intestinal Transplantation - Complications
• Other complications
– Graft versus host disease (GVHD)
– Post transplant lymphoproliferative disorder
(PTLD)
– Disease recurrence
• Pseudoobstruction
– Obstruction
– Chronic rejection
– Narcotic addiction (chronic pain)
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37. Post-transplant
Outcomes
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38. Intestinal Transplantation - Volume
U.S. intestinal transplant volume for last
decade200
180
160
140
120
100
80
60
40
20
0
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
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39. Intestinal Transplantation - Volume
• World Intestinal Transplant Registry (ITR)
– Worldwide database of all intestinal
transplants
– Between 2005 and 2007, 28 centers
wordwide reporting to the ITR performed 389
intestinal transplants on 377 patients
• In U.S. (Year 2010):
– 151 transplants (-16% from previous year)
– 17 centers with at least one transplant
– 6 centers with 10 or more transplants
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40. Intestinal Transplantation - Outcomes
• U.S. Adult intestinal transplant outcomes
Patient Survival
Age group 1-year 5-years
18 to 34 years 81% 70%
35 to 49 years 80% 63%
50 to 64 years 93% 38%
65+ years 100% N/A
From the Organ Procurement and Transplant Network (U.S.), 2002-2007
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41. Intestinal Transplantation – Costs
• Cost to maintain a patient on PN ranges from $75,000-$200,000 per
year
– Added costs of home nursing, support, equipment
• PN related complications result in an average of 1 major
hospitalization per year, and catheter related complications are
common and costly
• Intestinal transplantation has been shown to be a cost effective
therapy and is superior to continued PN in appropriately selected
patients
• Costs for intestinal transplantion, including the initial hospitalization
for the transplant range from $200,000-$500,000
• There are frequent hospital readmissions post-transplant, but these
admissions decrease markedly after the second year post-transplant
• The cost-benefit of transplantation reaches parity with PN after 2-3
years post-transplant and is more cost-effective thereafter
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