Intestinal transplantation            Dr. Richard S. Mangus, MD MS FACS              Assistant Professor of Surgery       ...
Intestinal Failure           Definition and Etiologies09/25/12                               2
Intestinal Failure - Definition• Failure of digestion and absorption• Inability of the intestinal tract to maintain adequa...
Intestinal Failure - Etiology                         Children  • Short gut (necrotizing enterocolitis, others)  • Intesti...
Intestinal Failure - Etiology                     Adults  • Short gut  • Mesenteric thrombosis (arterial or venous)  • Tra...
Intestinal Failure           Management issues09/25/12                        6
Intestinal Failure - Management  • Medically or surgically alter the remaining    intestine to compensate for inadequate  ...
Parenteral nutrition (PN)    •       First line therapy    •       Requires long term central venous access    •       Lab...
Parenteral nutrition – complications • Catheter related sepsis:           – Standard site infection           – Seeding fr...
Parenteral nutrition – complications  • Loss of vascular access           – 6 primary sites for vascular access           ...
Parenteral nutrition – complications  • Cholestatic liver disease           – Progressive cholestasis and cirrhosis       ...
Parenteral nutrition – complications  • Cholestatic liver disease (continued)           – Liver function tests in short gu...
Parenteral nutrition – FAILURE  • Medicare approved criteria for PN failure:           – Impending/overt liver failure due...
Intestinal Transplantion           Transplant options09/25/12                          14
Intestinal transplantation  • Advantages:           – Replace normal intestinal anatomy, continuity           – Patient ab...
Intestinal transplantation  • Disadvantages:           – Risks of major surgery           – Risk of rejection           – ...
Intestinal Transplantation - surgery  • Intestinal transplant options:           – Isolated intestinal transplant         ...
Intestinal Transplantation - surgery           • Surgical considerations:             – Organs to include             – Co...
Intestinal Transplantation  • Intestinal transplant : Recipient    operation09/25/12                                19
Intestinal Transplantation  • Isolated intestinal transplant           – Indication: Intestinal failure in the absence of ...
Intestinal Transplantation  • Isolated intestinal    transplant09/25/12                         21
Intestinal Transplantation  • Isolated intestinal    transplant09/25/12                         22
Intestinal Transplantation  • Isolated intestinal    transplant09/25/12                         23
Intestinal Transplantation  • Modified multivisceral transplant           – Indication: Intestinal failure in the absence ...
Intestinal Transplantation  • Modified    multivisceral    transplant09/25/12                         25
Intestinal Transplantation  • Modified multivisceral transplant09/25/12                                26
Intestinal Transplantation  • Multivisceral transplant           – Indication: Intestinal failure with liver failure      ...
Intestinal Transplantation  • Multivisceral    transplant09/25/12                         28
Intestinal Transplantation• Multivisceral transplant:  – Liver / intestine    transplant (+/- pancreas)09/25/12           ...
Intestinal Transplantation  • Multivisceral    transplant09/25/12                         30
Intestinal Transplantation  • Multivisceral    transplant09/25/12                         31
Intestinal Transplantation  • Multivisceral    transplant09/25/12                         32
Intestinal Transplantation  • Non-traditional indications:           – Diffuse mesenteric thrombosis           – Benign/ l...
Post-transplant care           Complications09/25/12                          34
Intestinal Transplantation - Rejection  • Rejection           – Isolated and modified multivisceral (liver             exc...
Intestinal Transplantation - Complications  • Other complications           – Graft versus host disease (GVHD)           –...
Post-transplant           Outcomes09/25/12                     37
Intestinal Transplantation - Volume           U.S. intestinal transplant volume for last           decade200              ...
Intestinal Transplantation - Volume  • World Intestinal Transplant Registry (ITR)           – Worldwide database of all in...
Intestinal Transplantation - Outcomes  • U.S. Adult intestinal transplant outcomes                                     Pat...
Intestinal Transplantation – Costs• Cost to maintain a patient on PN ranges from $75,000-$200,000 per  year   – Added cost...
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7 mangus intestinal transplantation

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7 mangus intestinal transplantation

  1. 1. Intestinal transplantation Dr. Richard S. Mangus, MD MS FACS Assistant Professor of Surgery Contact: rmangus@iupui.edu09/25/12 1
  2. 2. Intestinal Failure Definition and Etiologies09/25/12 2
  3. 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 area09/25/12 3
  4. 4. Intestinal Failure - Etiology Children • Short gut (necrotizing enterocolitis, others) • Intestinal atresia • Midgut volvulus • Gastroschisis • Hirschprung’s disease • Microvillus inclusion disease09/25/12 4
  5. 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)09/25/12 5
  6. 6. Intestinal Failure Management issues09/25/12 6
  7. 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 transplantation09/25/12 7
  8. 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 disease09/25/12 8
  9. 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 dwell09/25/12 9
  10. 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 / narrowing09/25/12 10
  11. 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 lipids09/25/12 11
  12. 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 patients09/25/12 12
  13. 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.09/25/12 13
  14. 14. Intestinal Transplantion Transplant options09/25/12 14
  15. 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 injury09/25/12 15
  16. 16. Intestinal transplantation • Disadvantages: – Risks of major surgery – Risk of rejection – Risks of life-long immunosuppression • Infections • Cancers • Renal failure • Graft versus host disease09/25/12 16
  17. 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 • +/- kidney09/25/12 17
  18. 18. Intestinal Transplantation - surgery • Surgical considerations: – Organs to include – Composite or separate – Whole or reduced size – Arterial inflow – Venous outflow – Enteric connection09/25/12 18
  19. 19. Intestinal Transplantation • Intestinal transplant : Recipient operation09/25/12 19
  20. 20. Intestinal Transplantation • Isolated intestinal transplant – Indication: Intestinal failure in the absence of any other organ failure • Normal function of liver, stomach, pancreas09/25/12 20
  21. 21. Intestinal Transplantation • Isolated intestinal transplant09/25/12 21
  22. 22. Intestinal Transplantation • Isolated intestinal transplant09/25/12 22
  23. 23. Intestinal Transplantation • Isolated intestinal transplant09/25/12 23
  24. 24. Intestinal Transplantation • Modified multivisceral transplant – Indication: Intestinal failure in the absence of liver failure • Normal function of liver • Dysfunction of stomach, intestine, +/- pancreas09/25/12 24
  25. 25. Intestinal Transplantation • Modified multivisceral transplant09/25/12 25
  26. 26. Intestinal Transplantation • Modified multivisceral transplant09/25/12 26
  27. 27. Intestinal Transplantation • Multivisceral transplant – Indication: Intestinal failure with liver failure • Dysfunction of liver and intestine • +/- dysfunction of stomach and pancreas09/25/12 27
  28. 28. Intestinal Transplantation • Multivisceral transplant09/25/12 28
  29. 29. Intestinal Transplantation• Multivisceral transplant: – Liver / intestine transplant (+/- pancreas)09/25/12 29
  30. 30. Intestinal Transplantation • Multivisceral transplant09/25/12 30
  31. 31. Intestinal Transplantation • Multivisceral transplant09/25/12 31
  32. 32. Intestinal Transplantation • Multivisceral transplant09/25/12 32
  33. 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 disorders09/25/12 33
  34. 34. Post-transplant care Complications09/25/12 34
  35. 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 rejection09/25/12 35
  36. 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)09/25/12 36
  37. 37. Post-transplant Outcomes09/25/12 37
  38. 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 201009/25/12 38
  39. 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 transplants09/25/12 39
  40. 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.), 2002-200709/25/12 40
  41. 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 thereafter09/25/12 41
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