Intestinal Transplantation

Updated: Jan 18, 2017
  • Author: Colin P Dunn, MA; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Overview

Practice Essentials

Intestinal transplantation has evolved in the past few decades from an experimental procedure to what is currently considered the only long-term option for patients with intestinal failure who have developed irreversible complications associated with the long-term use of parenteral nutrition. The number of intestinal transplants performed has increased sharply, from five in 1990 to 146 in 2016 in the United States alone, according to the Organ Procurement and Transplantation Network. Unfortunately, mismatch between supply and demand has led to increased waiting times for potential recipients, especially those younger than 1 year of age. [1]

With the increased number of intestinal transplants has come a remarkable improvement in outcomes, thanks to progress in various aspects of organ preservation, surgical technique, immunosuppression, and postoperative management.

Short gut syndrome (68% of cases) and functional bowel problems (15%) are the major sources of intestinal failure leading to intestinal transplantation. [2] Rare indications include vascular abdominal catastrophes and selected low-grade neoplastic tumors (eg, neuroendocrine pancreatic tumors and desmoids involving the mesenteric root). [3]

 

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Background

As with the transplantation of other organs, the history of intestinal transplantation begins with Carrel and his description of a method of performing vascular anastomosis. [4, 5] In 1959, the first canine model of intestinal transplantation was reported by Lillihei and coworkers at the University of Minnesota. [6] The first intestinal transplant in humans was performed by Deterling in Boston in 1964 (unpublished data). The first reported human intestinal transplant was performed by Lillihei and coworkers in 1967. [7] Before 1970, eight clinical cases of small-intestine transplantation were reportedly performed worldwide; maximum graft survival time was 79 days, and all patients died of technical complications, sepsis, or rejection.

In 1988 Deltz and coworkers in Kiel, Germany, performed what is considered to be the first successful intestinal transplant. [8] Soon after, other successful outcomes were reported by the groups headed by Goulet and coworkers in Paris [9] and Grant and coworkers in London, Canada, who had established the first intestinal transplant programs. [10, 11] A total of 15 isolated small-intestine transplantations were performed from 1985-1990 using cyclosporine. Graft survival time in these cases ranged from 10 days to 49 months.

 

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History of the Procedure

Waitlist and Transplantation Trends

The incidence of intestinal failure with complications of total parenteral nutrition (TPN) is difficult to measure. From studies of TPN-dependent patients, the incidence of irreversible intestinal failure is estimated to be 2-3 cases per million persons per year. [12, 13, 14, 15, 16]

As of January 2017, the Organ Procurement and Transplant Network (OPTN) listed 275 patients awaiting intestinal transplantation. [1] Median time on the waiting list varies by patient age, but overall has increased as more patients are listed and fewer patients are transplanted. For example,  median waiting time for patients younger than 1 year increased from 655 days in 2007-2010 to 1253 days in 2011-2014; for patients 1–5 years of age, median waiting time increased from 224 days to 372 days during those years. [1]

Nonetheless, death on the waiting list is rarer; patients are being transplanted when they are less ill. The proportion of patients transplanted from an intensive care unit decreased from 13.1% to 2.8% from 2002 to 2012, respectively. As of 2012, 90% of intestinal transplant recipients were not hospitalized before transplant. The pretransplant mortality rate decreased from 51 per 100 wait-list years in 1998-1999 to 6.7 per 100 wait-list years for patients listed in 2010-2012. [17]

Although the median time to transplant does not appear to be dramatically influenced by ethnicity, race, gender, or blood group, some differences are noted. The median time to transplant tends to be longer for males than females. Currently, a greater percentage of African Americans, Hispanics, and Asians are on the waiting list. However, Caucasians still make up the majority of waitlisted patients, at 59.5% total.

The age distribution of transplant candidates has changed from primarily less than 6 years of age to equal parts less than 6 years and greater than 18 years. [17] Short gut syndrome still represents most waiting list primary diagnoses. In 2012, there were 44 transplants per 100 wait-list years for adults and pediatric transplant candidates had 32 transplants per 100 patient-years. 15% were removed from the waiting list because their condition improved and 11.6% were removed from the waiting list because they had died.

In 2012, the 90-day graft failure rate was 15.7%. Ninety-day graft failure rates have remained relatively unchanged since the year 2003.

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Indications

Intestinal failure is characterized by the inability to maintain protein energy, fluid, electrolyte, or micronutrient balance due to GI disease when on a normal diet. Intestinal failure ultimately leads to malnutrition and even death if the patient does not receive parenteral nutrition or become a recipient of an intestinal transplant. Worldwide, the leading cause of intestinal failure is short bowel syndrome caused by surgical removal. Short gut syndrome (68%) and functional bowel problems (15%) are two major indications for intestinal transplantation. [2]

The leading causes of intestinal failure differ between adult and pediatric populations. In children, the following are the leading causes of intestinal failure:

The following are the leading causes of intestinal failure in adults:

  • Crohn disease
  • Superior mesenteric artery thrombosis
  • Superior mesenteric vein thrombosis
  • Trauma
  • Desmoid tumor
  • Volvulus
  • Pseudo-obstruction
  • Massive resection secondary to tumor
  • Radiation enteritis

Parenteral nutrition is the current standard of care for patients with intestinal failure. Nevertheless, the long-term use of parenteral nutrition is often associated with potentially life-threatening complications, including the following [18] :

  • Catheter-related sepsis
  • Catheter-related thrombosis
  • Severe dehydration
  • Metabolic derangements
  • Loss of sites for vascular access
  • Intestinal failure–associated liver disease (IFALD)

IFALD is partly caused by omega-6 fatty acids in parenteral nutrition formulas, which can be synthesized into inflammatory molecules. IFALD can range from steatohepatitis, cholestasis, or hepatic fibrosis to end-stage liver disease. Children are more likely to have cholestatic liver disease than steatohepatitis [19] . Severe liver injury has been reported in as many as 50% of patients with intestinal failure who receive parenteral nutrition for longer than 5 years; this is typically fatal. If patients have life-threatening infections, IFALD, or lose their venous access, 1 year mortality is 70% without intestinal transplantation [20] .

As an early alternative to transplantation or total parenteral nutrition (TPN) for patients with short bowel syndrome, surgical bowel lengthening without transplant may be attempted. This requires the serial transverse enteroplasty (STEP) or longitudinal intestinal lengthening and tailoring (LILT) procedures.

STEP and LILT are particularly successful in patients with decreased transit times and dilated bowel. These procedures lengthen the small bowel while keeping the total surface area the same. Bowel is either split lengthwise or cut obliquely at multiple points. This will lengthen the bowel and shrink the luminal diameter [21] . If successful, this may reduce the amount of TPN required, or negate its use altogether. In one study, 27 children underwent the LILT procedure. Overall survival was 92%, and more than 90% of survivors no longer required parenteral nutrition [22] .

If patients are not acceptable candidates for STEP or LILT, sometimes a reversal of small bowel direction may effectively increase transit times. If none of these operations are successful, the standard of care is TPN. Intestinal transplantation should be recommended in lieu of TPN in patients with failure of the parenteral nutrition, as indicated by the following:

  • Impending or overt liver failure secondary to IFALD
  • Thrombosis of two or more central veins
  • Two or more episodes per year of systemic sepsis secondary to line infections, or a single episode of fungal sepsis [23]
  • Frequent episodes of severe dehydration

Additional indications for intestinal transplantation include the following:

  • High risk of death
  • Severe short bowel syndrome (gastrostomy, duodenostomy, residual small bowel [< 10 cm in infants, < 20 cm in adults])
  • Intestinal failure with frequent hospitalizations, narcotic dependency, or pseudoobstruction
  • Patient unwillingness to accept long-term parenteral nutrition

The advent of ethanol lock therapy [24, 25] has reduced the number of catheter-related infections dramatically. This may reduce the number of patients with recurrent infections necessitating intestinal transplant. Flushing lines with a 70% ethanol solution between feedings led to a decline in the number of catheter-related blood stream infections from 10.1 per 1000 catheter-feed days to 2.9 in a retrospective cohort of 31 patients. [25] Description of adverse reactions have been mixed, however, as catheter thrombosis occurred in some patients. [24]

In addition to intestine-only and intestine-liver transplants, multivisceral transplants represent a third type of intestinal transplant. The United Network for Organ Sharing (UNOS) defines a multivisceral transplant as one that includes the intestine and liver and either the pancreas or kidney; however, several combinations may be used, depending on the extent of disease (see the images below).

Liver-small bowel graft, including the pancreas. Liver-small bowel graft, including the pancreas.
Multivisceral graft, including stomach-liver-pancr Multivisceral graft, including stomach-liver-pancreas-small bowel and right colon.
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Contraindications

The contraindications of intestinal transplantation are essentially the same as is seen in other types of transplants. Examples include the following:

  • Significant coexistent medical conditions that have no potential for improvement following transplantation
  • An active uncontrolled infection or malignancy that would not be eliminated by the transplant process
  • Psychosocial factors (eg, the lack of capability to assume the responsibilities of the day-to-day management following the transplant or the absence of family support)
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