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Intestinal transplantation Dr. Richard S. Mangus, MD MS FACS Assistant Professor of Surgery Contact: rmangus@iupui.edu 09/25/12

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Intestinal Failure Definition and Etiologies

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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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Intestinal Failure - Etiology Children • Short gut (necrotizing enterocolitis, others) • Intestinal atresia • Midgut volvulus • Gastroschisis • Hirschprung’s disease • Microvillus inclusion disease 09/25/12

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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

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Intestinal Failure Management issues

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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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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 – – – – –

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Infections Loss of vascular access Electrolyte abnormalities Nutritional deficiencies (trace metals, other) Liver disease 8


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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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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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 09/25/12

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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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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

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Intestinal Transplantion Transplant options

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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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Intestinal transplantation • Disadvantages: – Risks of major surgery – Risk of rejection – Risks of life-long immunosuppression • • • •

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Infections Cancers Renal failure Graft versus host disease

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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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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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Intestinal Transplantation â&#x20AC;˘ Intestinal transplant : Recipient operation

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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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Intestinal Transplantation â&#x20AC;˘ Isolated intestinal transplant

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Intestinal Transplantation â&#x20AC;˘ Isolated intestinal transplant

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Intestinal Transplantation â&#x20AC;˘ Isolated intestinal transplant

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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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Intestinal Transplantation â&#x20AC;˘ Modified multivisceral transplant

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Intestinal Transplantation â&#x20AC;˘ Modified multivisceral transplant

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Intestinal Transplantation • Multivisceral transplant – Indication: Intestinal failure with liver failure • Dysfunction of liver and intestine • +/- dysfunction of stomach and pancreas

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Intestinal Transplantation â&#x20AC;˘ Multivisceral transplant

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Intestinal Transplantation â&#x20AC;˘ Multivisceral transplant: â&#x20AC;&#x201C; Liver / intestine transplant (+/- pancreas)

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Intestinal Transplantation â&#x20AC;˘ Multivisceral transplant

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Intestinal Transplantation â&#x20AC;˘ Multivisceral transplant

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Intestinal Transplantation â&#x20AC;˘ Multivisceral transplant

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Intestinal Transplantation • Non-traditional indications: – Diffuse mesenteric thrombosis – Benign/ low grade malignant tumors involving the mesenteric root • Neuroendocrine tumors (carcinoid, insulinoma, others) • Desmoid tumors

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Abdominal catastrophes / fistulas Radiation enteritis Trauma Enteropathies / dysmotility disorders 33


Post-transplant care Complications

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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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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

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Post-transplant Outcomes

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Intestinal Transplantation - Volume U.S. intestinal transplant volume for last decade 200 180 160 140 120 100 80 60 40 20 0

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2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

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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 09/25/12

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Intestinal Transplantation - Outcomes â&#x20AC;˘ 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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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 09/25/12

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