Memorial Hermann-Texas Medical Center

Texas Liver Center & Intestinal Rehabilitation Clinic

Reference for Physicians

History of Intestinal Transplantation
Indications for Intestinal Transplantation
Transplantation Procedures

History of Intestinal Transplantation

Intestinal transplantation (IT) has its roots in the very beginnings of the field of organ transplantation. Alexis Carrel was the first one to perform this procedure in dogs, and used this work to elaborate on the techniques of vascular surgery that resulted in the Nobel Prize in 1912. Clinical trials were attempted in the 1960s.

During this era, only 12 intestinal-type transplants were performed with no long-term survivors due to intractable acute rejection from inadequacy of the available immunosuppression at that time. With total parenteral nutrition (TPN) not yet available for patients without a functional gastrointestinal tract, the drive toward IT was the extremely poor outcome for patients undergoing extensive bowel resections.

With the development and widespread use of TPN in 1967 by Stanley Dudrick (former University of Texas Medical School at Houston Department of Surgery Chairman), further development in IT awaited advances in immunosuppression. In the late 1980s, because of the high mortality rates seen in the subpopulation of patients with major complications related to chronic TPN use, a resurgence in IT was seen under cyclosporine. However, long-term success was still limited by acute rejection at this time. With the development and routine clinical use of tacrolimus beginning in 1994, results improved dramatically.

With further technical and immunosuppressive advances since these early case reports, small bowel transplantation has progressed from an experimental endeavor to the accepted therapy for end-stage intestinal failure secondary to the short-gut syndrome, metabolic or functional disorders, and for some tumors (see “indications”). The results of intestinal transplantation have improved dramatically since 2001, and over 1,000 intestinal transplants have been performed world-wide, with over 900 in the United States.
   

Indications for Intestinal Transplantation

Intestinal transplantation (IT) is indicated in the following circumstances in patients with chronic intestinal failure (IF):

• Patients facing life-threatening complications of TPN for intestinal failure (IF) from any cause (e.g., recurrent, severe line infections or vascular thrombosis)
• Patients with chronic IF who have advance liver disease (i.e., PNALD or other form of cirrhosis)
• Patients with chronic IF who have a very poor quality of life
• Patients with dysmotility syndromes, such as chronic intestinal pseudo-obstruction or aganglionosis
• Pediatric patients with congenital malabsorptive conditions (e.g., microvillus inclusion disease)
• Patients with certain unresectable tumors in highly select cases (e.g., desmoids, GISTs)

In many cases, the complications of TPN threaten the patient's life (e.g., irreversible liver failure) or make the administration of TPN difficult or impossible (e.g., loss of central access sites or life-threatening catheter sepsis). The latter indirectly threatens the patient's only route of nutrition and, therefore, long-term survival. Both lead to a shortened lifespan.

Chronic pain from dysmotility syndromes or recurrent or persistent hospitalizations leads to often intolerable quality of life. When post-transplant survival is significantly better or of greater quality in a patient with IF of any cause, transplantation should be considered.

Specific indications for referral to IRTC for IT evaluation:

Early referral is often the key to a successful patient outcome. Below is a list of problems in a patient with chronic IF that should prompt referral to the IRTC. These are not the only scenarios that can require IT evaluation, so if there are questions please contact the IRTC for further information.

• Ultrashort gut syndrome from massive resection (<30-40 cm in adult or <10 cm in infant)
• Non-reconstructable GI tract from massive resection (i.e., permanent gastro-colonic discontinuity)
• Jaundice (persistent bilirubin elevation > 3 mg/dl)
• Evidence of portal hypertension (large spleen, thrombocytopenia, GI bleeding)
• Any stage of fibrosis on liver biopsy
• More than two central line infections in a 6-month period
• Any central line infection that results in organ failure or dysfunction (e.g., requiring ICU support), especially when associated with liver failure
• Development of multidrug resistance with central line infections
• Development of metastatic foci of infections from recurrent central line infections
• Thrombosis of greater than two vascular access sites in patients > 20 Kg
• Thrombosis of any vascular access site in patients < 20 Kg
• Repeated or chronic hospitalization for TPN-related issues (dehydration, electrolyte disturbances, renal failure)
• Narcotic addiction or a severely depressed quality of life in a patient with dysmotility syndromes or a non-reconstructable GI tract
• Very poor quality of life as assessed by the patient or caregiver

Contraindications:

1. Uncontrolled malignancy outside of the intestinal tract or liver
2. Severe cardiopulmonary disease that would make the transplant procedure's risk prohibitive
3. Severe, irreversible neurologic disease that markedly impairs function
4. Uncontrollable or active infection outside the liver or bile ducts
5. Untreatable or unstable psychiatric conditions (e.g., severe pre-morbid depression, bipolar disorder or psychosis that is poorly treated)
6. Active substance abuse (a history of abuse is not a contraindication pending assessment by a substance abuse specialist)
7. HIV positivity
8. Extremely poor social support that is not remediable and precludes adequate post-transplant independence

There are four types of transplantation procedures that may be options for patients referred to the IRTC.

• Isolated intestinal transplantation: This is indicated for patients with chronic IF who do not have advanced liver disease, but have suffered potentially life-threatening complications of TPN. This involves providing the recipient with a small intestinal graft from a deceased donor. If done with patients who have early liver disease from TPN, the changes in the liver will reverse with successful transplantation and freedom from TPN.
• Combined liver intestinal transplantation: This is indicated for patients with chronic IF who have advanced or end-stage liver disease, which is a potentially life-threatening complications of TPN. The liver failure and TPN-dependence is treated with a combined liver and intestinal graft from a deceased donor. At least 70 percent of patients receiving IT also need a liver transplant.
• Multivisceral transplantation: This is indicated for patients with chronic IF who have advanced or end-stage liver disease, and also need pancreas and or gastric transplantation. This procedure is rarely indicated.
• Isolated liver transplantation: This is indicated for patients who have advanced or end-stage liver disease and short-gut syndrome without true IF because they have a good chance for intestinal adaptation. almost all of these patients are children younger than five capable of absorbing 50 percent or more of their calories through an enteral or oral route. Restoring normal liver function and treating portal hypertension often leads to complete adaptation of the gut. Also, the results of isolated liver transplantation are better. Unfortunately, few patients are good candidates for this procedure. However, with early referral in such patients an isolated liver transplant can be considered.

The results of intestinal transplantation have improved dramatically since the 1990s. Currently, the survival rate one year after an IT is at least 75 percent. The three-year survival rate is 50-60 percent. This is almost twice the survival rate without a transplant for most patients being transplanted today.

Also, 80-90 percent of survivors are free of TPN at 6 months, and 90 percent are quite satisfied by their post-transplant quality of life. With development of more effective and less toxic anti-rejection drugs and earlier diagnosis of transplant rejection, these results are likely to improve. But late loss of life or the transplanted bowel due to complications does occur, so patients must have a firm indication for IT prior to choosing this option.