7_mangus_intestinal transplantation

09/25/12 1

Intestinal transplantation

Dr. Richard S. Mangus, MD MS FACSAssistant Professor of SurgeryContact: [email protected]

09/25/12 2

Intestinal Failure

Definition and Etiologies

09/25/12 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

09/25/12 4

Intestinal Failure - Etiology

Children• Short gut (necrotizing enterocolitis, others)

• Intestinal atresia

• Midgut volvulus

• Gastroschisis

• Hirschprung’s disease

• Microvillus inclusion disease

09/25/12 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 6

Intestinal Failure

Management issues

09/25/12 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

09/25/12 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

09/25/12 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

09/25/12 10


• Loss of vascular access

– 6 primary sites for vascular access • Jugular, subclavian, femoral

– Thrombus formation• May require anticoagulation• Heparin dwell

– Vein sclerosis / narrowing

09/25/12 11


• 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 12


• 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

09/25/12 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 14

Intestinal Transplantion

Transplant options

09/25/12 15


• 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

09/25/12 16


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

• Infections• Cancers• Renal failure• Graft versus host disease

09/25/12 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

09/25/12 18

Intestinal Transplantation - surgery

• Surgical considerations:– Organs to include– Composite or separate– Whole or reduced size– Arterial inflow– Venous outflow– Enteric connection

09/25/12 19

Intestinal Transplantation

• Intestinal transplant : Recipient operation

09/25/12 20


• Isolated intestinal transplant– Indication: Intestinal failure in the absence of

any other organ failure• Normal function of liver, stomach, pancreas

09/25/12 21


• Isolated intestinal transplant

09/25/12 22



09/25/12 23



09/25/12 24

Intestinal Transplantation• Modified multivisceral transplant

– Indication: Intestinal failure in the absence of liver failure• Normal function of liver• Dysfunction of stomach, intestine, +/- pancreas

09/25/12 25

Intestinal Transplantation• Modified

multivisceral transplant

09/25/12 26


• Modified multivisceral transplant

09/25/12 27


• Multivisceral transplant– Indication: Intestinal failure with liver failure

• Dysfunction of liver and intestine• +/- dysfunction of stomach and pancreas

09/25/12 28


• Multivisceral transplant

09/25/12 29

Intestinal Transplantation• Multivisceral transplant:

– Liver / intestine transplant (+/- pancreas)

09/25/12 30

Intestinal Transplantation• Multivisceral

transplant

09/25/12 31


transplant

09/25/12 32


transplant

09/25/12 33


• 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

09/25/12 34

Post-transplant care

Complications

09/25/12 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

09/25/12 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 37

Post-transplant

Outcomes

09/25/12 38

Intestinal Transplantation - Volume

020406080

100120140160180200

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

U.S. intestinal transplant volume for last decade

09/25/12 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

09/25/12 40

Intestinal Transplantation - Outcomes

• U.S. Adult intestinal transplant outcomes

Patient Survival

Age group 1-year 5-years18 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

09/25/12 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

7_mangus_intestinal transplantation

Documents