Introduction
Intestinal transplantation (ITx) was first attempted in the 1970s in children with intestinal failure (IF) for whom intravenous nutrition was not available. The early efforts did not meet with long-term success because of lack of adequate immunosuppression. The first successful adult combined liver and small bowel transplant was performed in Canada in 1988; the first successful isolated ITx was in 1989 in Paris in a baby with short bowel syndrome. The advent of FK506, later tacrolimus, in the 1990s, resulted in a surge in the number of intestinal transplants performed worldwide ( Fig. 13.1 ). There were many challenges to overcome because of the intestine harboring more than 80% of the body’s immune cells and billions of bacteria in the microbiota, resulting in a complex interplay with high-intensity immunosuppression. The international Intestinal Transplant Registry (ITR) latest data reported on 3452 patients including 1843 children, 1107 receiving liver-inclusive grafts (797 combined liver-small bowel, 310 multivisceral); only 812 of these children were alive at last follow-up, not all of them with their graft. The 10-year patient survival was about 50% to 60%; the graft survival was about 40% to 50%. These numbers reflect the difficulties of this rare technique with slowly improving long-term results.
Indications
Intestinal Failure
IF is the reduction of functional gut mass below the threshold of maintenance of metabolic functions in adults and normal growth in children. The treatment of choice of irreversible IF is home parenteral nutrition (PN), for which mortality in children is very low. IF is a rare disease; the patients’ care should therefore be shared (whether physically or via web consulting) with an expert center for intestinal rehabilitation, where all medical and surgical options can be discussed.
ITx is the treatment of total and irreversible IF, associated with life-threatening complications of PN. The child should receive at least 80% of his nutritional needs in PN without any hope of future weaning of PN.
IF is obviously definitive if the child has ultrashort bowel syndrome or severe microvillous inclusion disease. However, intestinal adaptation may be possible in not-so-short bowel syndrome, and the evolution of IF is variable in other enteropathies or chronic intestinal pseudo-obstruction syndromes (CIPOSs).
Causes of Intestinal Failure
- a-
Short bowel syndrome, the most frequent indication in the ITR (61%): intestinal atresia, necrotizing enterocolitis, gastroschisis, volvulus, desmoid tumor;
- b-
Mucosal diseases or congenital enteropathies (9% in the ITR): microvillous inclusion disease, tufting enteropathy; and
- c-
Motility disorders (19% in the ITR): long-segment Hirschsprung disease, chronic intestinal pseudo-obstruction syndrome (CIPOS).
Complications of Home Parenteral Nutrition Limiting Its Long-Term Performance
- a-
Loss of vascular access: the number of thrombosed major veins is discussed (two in the first criteria, number recently challenged ), but it should not wait until the last central line. Care of central lines, size, location, insertion, and management should be meticulous in patients with IF.
- b-
Recurrent or life-threatening infections from the central line or the digestive tract. Taurolidine or ethanol locks can be discussed, and continuous training of staff and caregivers is essential.
- c-
Progressive IF-associated liver disease (IFALD): ITx should be discussed before complications of cirrhosis such as bleeding. Prevention of IFALD is important from the onset of IF: preservation of the enterohepatic cycle and gut motility, prevention of infections, adequate and cycled PN, and control of fat emulsions.
- d-
Severe hydroelectrolytic disorders because of major digestive losses, such as in microvillous atrophy.
- e-
Growth failure despite adequate calorie supply.
- f-
Inability to perform PN at home for social or medical reasons; ITx should be discussed before the development of irreversible psychological disorders.
- g-
Psychological intolerance to home PN: this is the most difficult indication. Patients and families see ITx as the relief of PN constraints (“dog on leash”) and hear only part of the ITx ones (“leash is transparent”). But if home PN is unbearable, it will be inadequately managed, with new complications. Repeated explanations and time should be given.
Timing of Transplantation
General Evaluation
The timing of referral for ITx is critical, and early dialogue with an ITx center is recommended. Waiting times are long, and the children should be referred before severe complications threaten their lives in the short term. On the waiting list for ITx, close collaboration between centers should be maintained and PN perfectly monitored, as additional complications may impair the outcomes.
The evaluation is the same as for another organ transplantation. However, some particularities are unique, such as the small numbers of centers, which are present in certain countries only. Even more than other organ transplantations, ITx is not a cure, and long-term complications are frequent. ITx should reasonably not be performed if the follow-up is not secured.
The psychosocial evaluation is an important part for families with difficult histories and more difficult weeks or months of hospitalization ahead.
Kidney Function
The glomerular filtration rate (GFR) should be measured (iohexol, Chrome EDTA [CrEDTA], etc.), and not calculated. The pre-ITx risk factors for renal failure are many: pre-existing disease (Hirschsprung and renal dysplasia, CIPOS and megacystis, microvillous inclusion disease and dehydration, etc.), antibiotics, and so on. After ITx, these are immunosuppressive drugs, antibiotics, and hemodynamic or septic shock. If the GFR is below 50 mL/mn/1.73m 2 , a combined kidney transplantation may be discussed.
Infections
Patients often harbor multiresistant bacteria. Bacterial and fungal screens should be repeated during the waiting time and antibiotics spared if possible. The child should receive all vaccines, especially live ones, that cannot be given after ITx.
Anti–Human Leukocyte Antigen Immunization and Immunological Risk
Pre-ITx antihuman leukocyte antigen (HLA) immunization is frequent in these patients who were multioperated. In many countries the waiting time is too long for a pre-ITx desensitization, whose efficiency is not demonstrated. For combined liver–small bowel ITx, because of organ shortage and lower risk of post-ITx humoral rejection, the decision to accept the graft does not depend on HLA. An isolated intestine, however, should not be accepted if the recipient has pre-ITx donor-specific antibodies (DSAs). The prevention of humoral rejection post-ITx follows the same protocols as for kidney transplantation: screening for DSA, intravenous immunoglobulins, and plasma exchanges if DSAs appear or increase.
Surgical Considerations and Graft Selection
General
The median age at ITx was previously 2 years, but nowadays it is about 4 to 5 years because of better care of neonates with IF. For stereometric reasons, the donor should therefore be a child, especially when the liver or colon are included in the graft. The reduced intestine from an adult fits an older child who does not need a colon transplantation. The liver can be reduced, with the added risks of segmental graft and increased ischemia. The cold ischemic time for the intestine should be less than 6 hours.
HLA matching is impossible because of organ shortage and, in certain countries, time until HLA results become available. However, although humoral (antibody-mediated) rejection has emerged as a significant factor of graft survival, the impact of HLA matching on the outcome of liver-containing grafts is unclear.
The Small Bowel
An isolated small bowel has been transplanted in 46% of all patients reported to the ITR, 37% in children. The proximal anastomosis is duodeno- or jejuno-jejunal. The graft portal vein is connected to the recipient’s inferior vena cava.
A stoma is created at the ileal end of the graft to monitor the function (stool amount and aspect) and easily perform biopsies. The ileostomy is taken down several months after ITx in the stable state. If needed (anorexia), a gastrostomy can be created.
The Liver
The liver and small bowel have been transplanted together in 29% of patients in the ITR, 43% in children. Nowadays in the United States, the same number of patients, whatever their age, are waiting for an isolated ITx or a combined ITx. The decision for liver inclusion depends on the degree of IFALD. A liver biopsy is usually performed pre-ITx. In unclear situations, wedge hepatic pressure measurement may help to diagnose portal hypertension. The improvements in IF care made decompensated cirrhosis rare. The liver has a protective role against intestinal rejection and may therefore be a positive factor for long-term survival. However, the ITR results are not so clear, the interpretation of long-term results of small series with protocol changes is difficult, and the shortage of liver grafts makes the discussion theoretical.
The liver and small bowel (with or without colon) are retrieved together with the mesenterium, the portal system, and the bile ducts and transplanted as a whole. The graft pancreas was initially reduced to its head and is nowadays left intact. The proximal end of the graft duodenum is closed. The digestive anastomosis is between both proximal jejunums. A stoma is created at the ileal end of the graft to be closed later (see discussion earlier in the chapter). The recipient portal vein, draining the upper gastrointestinal tract, the spleen, the colon, and the rectum, is connected to the recipient inferior vena cava ( Fig. 13.2 A ).
Related posts:
What Is Different Between Pediatric and Adult Liver Transplantation?
Living Donor Liver Transplantation in Children
Immunological and Other Late Complications
Post-Operative Care After Liver Transplantation
Liver Transplantation for Acute Liver Failure in Children
Pediatric Liver Transplantation in South America: Incidence and Indications
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