Pediatric Intestinal Failure

REVIEW ARTICLE

Pediatric Intestinal Failure

C.P. Duggan and T. Jaksic

Intestinal failure has been defined as “the reduction of functional gut mass below the minimal amount
necessary for digestion and absorption adequate to satisfy the nutrient and fluid requirements for
maintenance in adults or growth in children.” An umbrella label, intestinal failure includes the surgical
short-bowel syndrome (intestinal resection for acquired or congenital gastrointestinal diseases,
leading to clinically significant malabsorption and requiring specialized nutritional therapy), as well as
disorders of gastrointestinal motility (e.g., intestinal pseudo-obstruction) and congenital enterocyte
disorders (microvillus inclusion disease, tufting enteropathy, and others). A New England Journal of
Medicine article reviews the natural history and management of pediatric intestinal failure due to the
surgical short-bowel syndrome.

Clinical Pearls
How does the intestine adapt to massive post-surgical bowel loss?
The process of intestinal adaptation to massive bowel loss has been described as a compensatory
process wherein the remaining bowel undergoes substantial structural and functional changes that
increase its absorptive capacity. Histologic hallmarks of the compensatory process include increased
villous height and crypt depth, with gross anatomical features that include bowel lengthening and
dilatation. Such adaptation is promoted by a combination of mechanical, humoral, and luminal factors,
and putative molecular signaling pathways are being actively investigated. It is thought that
aggressive enteral therapy enhances adaptation and prevents complications associated with
prolonged parenteral therapy.

What complications are associated with parenteral nutrition?

Meticulously administered fluid, electrolyte, and nutritional therapy, with both specialized parenteral
and enteral nutrition, is the mainstay of treatment for pediatric intestinal failure. Prolonged parenteral
nutrition is lifesaving but nevertheless may lead to numerous complications, including central
catheter–associated bloodstream infections, mechanical catheter–associated complications
(breakage or thrombosis), metabolic bone disease, and intestinal failure–associated liver disease.

Morning Report Questions

Q. What are some of the newer therapies being studied to treat pediatric intestinal failure due
to short-bowel syndrome?

A. Newer intravenous fat emulsions, one containing a four-lipid combination of soy, olive, fish, and
medium-chain oils and the other containing olive and soy oils were approved for use in adults by the
Food and Drug Administration in 2016 and 2013, respectively. The four-lipid product has undergone
preliminary evaluation in infants with early intestinal failure–associated liver disease (mean direct
bilirubin level, 1 to 3 mg per deciliter [17 to 50 μmol per liter]). In a multicenter pilot study (a blinded,
randomized, controlled trial comparing the four-lipid product with a soy-based lipid emulsion), the
conjugated bilirubin level was significantly lower in 11 infants who received the four-lipid product than
in 13 infants treated with the soy-based lipid emulsion, each for a mean duration of 8 weeks. Therapy
with gastrointestinal hormones to induce intestinal adaptation shows promise as a medical therapy for
intestinal failure. Glucagon-like peptide 2 (GLP-2) is a naturally occurring hormone secreted by
enteroendocrine cells in the distal ileum and colon. GLP-2 induces small-bowel epithelial proliferation
and delays gastric emptying.

Q. What surgical procedures may be used to treat pediatric intestinal failure?

A. Autologous intestinal reconstruction surgery aims to taper and lengthen the remaining bowel in
order to improve motility, enhance absorption, and limit bacterial overgrowth. The longitudinal
intestinal lengthening and tailoring procedure (LILT), commonly referred to as the Bianchi operation,
was first described in 1980. A simpler operation, serial transverse enteroplasty (STEP), was
developed more recently. Data from the International STEP Registry indicate that among patients in
whom standard bowel rehabilitation is not successful, 66% have improved enteral tolerance and 47%
are fully weaned from parenteral nutrition after undergoing the initial STEP procedure. These two
procedures have not been directly compared, although limited data appear to support the STEP
procedure, which is less technically difficult than LILT and can be repeated. Some children with
intestinal failure are candidates for intestinal or multivisceral transplantation. There are currently more
than 1000 living intestinal-transplant recipients in the United States, nearly half of whom underwent
transplantation as children.

Teaching Topic
A Man with Fever and Lymphadenopathy
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 25-2017: A 45-Year-Old Man with Headache, Fever, and Lymphadenopathy

A.S. LaCasce and Others

In any patient who has pathologically enlarged lymph nodes and systemic symptoms, lymphoma and
Castleman’s disease should be ruled out.

Clinical Pearls
Describe some of the features of angioimmunoblastic T-cell lymphoma.
Angioimmunoblastic T-cell lymphoma is the second most common peripheral T-cell lymphoma. This
disease arises from the peripheral helper T cell that aberrantly expresses the cell-surface marker
CD10 and is associated with plasmacytosis and polyclonal hypergammaglobulinemia. Constitutional
B symptoms, diffuse lymphadenopathy, and autoimmune manifestations are common features. The
median age at disease onset is 65 years.

What inflammatory condition can mimic angioimmunoblastic T-cell lymphoma?

Multicentric Castleman’s disease can be difficult to distinguish from angioimmunoblastic T-cell
lymphoma on clinical grounds.

Morning Report Questions

Q. What are some of the features of primary Epstein–Barr virus (EBV) infection?
A. Infectious mononucleosis is the clinical syndrome associated with acute EBV infection. EBV
infection typically occurs during one of two distinct time periods; the first wave of infection occurs
during early childhood, before the age of 5 years, and the second wave occurs during the second and
third decades of life. Most adults have been infected with EBV, and only 3 to 10% of adults older than
40 years of age have not been infected. As compared with children and young adults, older patients
with primary EBV infection are less likely to present with pharyngitis and are more likely to have
severe illness that necessitates hospitalization. Primary EBV infection is characterized by abnormal
results on flow cytometry of the peripheral blood, including an inverted CD4:CD8 ratio and frequent
down-regulation of certain pan–T-cell antigens. The presence of an expanded CD8+ T-cell population
corresponds to the presence of atypical-appearing lymphocytes on peripheral-blood smears. Biopsy
specimens of affected lymph nodes and tonsils show a number of morphologic features that mimic
the features of lymphoma, including architectural distortion, an immunoblastic proliferation with
cytologic atypia, and necrosis.

Figure 1.Imaging Studies.

Q. What subtypes of lymphoma are associated with EBV infection?

A. Several subtypes of aggressive lymphoma are associated with EBV infection, including Burkitt’s
lymphoma, diffuse large B-cell lymphoma, lymphomatoid granulomatosis, and angioimmunoblastic T-
cell lymphoma. However, these cancers are associated with latent, chronic EBV infection and not with
acute EBV mononucleosis. In a patient with EBV viremia and diffuse lymphadenopathy that is
worrisome for lymphoma, it is critical to perform viral serologic tests to rule out primary infection.

Archive of Teaching Topics »

QUOTE OF THE WEEK

“In this multicenter, randomized, placebo-controlled trial involving women with

singleton pregnancies who were identified by means of first-trimester screening as
being at high risk for preterm preeclampsia, the administration of aspirin at a dose of
150 mg per day from 11 to 14 weeks of gestation until 36 weeks of gestation was
associated with a significantly lower incidence of preterm preeclampsia than was
placebo.”

D.L. Rolnik and Others, Original Article,

“Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia”