I

Short Bowel Syndro

me/Intestinal Failure

ntestinal failure is defined by the inability to maintaingrowth and development by regular means of nutrition.The causes vary, but the most common is short bowel syn-

drome, as a result of resection of necrotic bowel in thecontext of complications of prematurity, or the expression

See related article, p ���

of congenital and developmental anomaliesof the gastrointestinal tract. Until the devel-

The author declares no conflicts of interest.

0022-3476/$ - see front matter. Copyright ª 2013 Mosby Inc.

All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2013.07.019

opment of techniques such as parenteral nutritional support,this diagnosis was fatal, or the prognosis and the outcomes ofall these patients were very poor.

Once we were able to find an alternate way to supply thesepatients with calories and nutrients, the prognosis dramati-cally changed but was accompanied by an abundance of com-plications and side effects from the infusion of alimentaryproducts via the intravenous route, which caused a majortoll on patient outcomes. In this issue of The Journal, Infan-tino et al1 present the current perspective on a large group ofpatients with the most severe form of short bowel syndrome,the so-called “ultra-short small bowel” category. Their re-ported experience is quite encouraging and positive.

We have had the opportunity to observe the developmentsin the care of the pediatric patient with intestinal failure,including the use of total parenteral nutrition, advances insurgical techniques and in organ transplantation, alongwith the development and discovery of different modalitiesand combination of nutrients to prevent complications.Therefore, it is rewarding to see how a systematic, careful,multidisciplinary, and particularly well-monitored manage-ment of these patients can produce such a positive result,namely intestinal adaptation and the ability to regain nutri-tional autonomy by the majority of these patients, obviatingthe need of intravenous supplementation.

The main goals in the management of these patientsinclude: (1) promotion of growth and development; (2)administration of a balanced and adequate diet; (3) mainte-nance of a good fluid and electrolyte balance; (4) preventionof infections; (5) prevention of liver disease; and (6) promo-tion of an optimal quality of life.

For the first 2 goals, the reported lessons and collectedexperience suggest the demonstration of adequate caloriesand balanced nutrients while avoiding excessive support,cycling the intravenous solutions, and starting the oral routeas soon as allowed by the postoperative course as well asmaximizing the enteral route without causing excessive os-motic losses as important. We have also learned that caloricneeds may be unique to individuals and that the assessmentof energy expenditure may be helpful in preventing the com-plications of overfeeding that also may interfere with motordevelopment in the developing infant.

Regarding the third goal, consideration of the multifacto-rial causes of malabsorption in short bowel syndrome,including acid hypersecretion, rapid intestinal transit, loss

of surface area, quality or impairment of the residual bowel,the presence of bacterial overgrowth, and bile-acid wasting, ishelpful in complementing the choice of therapies or thera-peutic agents.Specific pharmacologic therapies for the management of

short bowel syndrome are mainly aimed atreducing gastric secretion and decreasing

diarrhea both by decreasing a possible secretory componentand by increasing segmental contractions of the bowel todecrease transit time. Reduction of diarrhea and water andelectrolyte losses also includes the control of bacterial over-growth with the use of antibiotics and perhaps pre- and pro-biotics. Manipulation of the intestinal flora in short gut mayalso be used to prevent reabsorption of oxalate from the co-lon with the prevention of renal stones and a less clear objec-tive, such as the prevention of bacterial translocation andreduced intravenous catheter-associated infections.2

The use of promotility agents that increase the segmentalcontractions, thus reducing transit time, like opiates, diphe-noxylate, or loperamide and, in certain clinical settings, theuse of long-acting forms of somatostatin (octreotide), areuseful in preventing excessive losses. Hypergastrinemia as aresult of increased stimulation by the infusion of amino acidsand decreased catabolism of this hormone in short gut, withthe subsequent increase in its half life, leads to gastric hyper-secretion, which in turn reduces the coefficient of absorptionof fats by decreasing mycelar formation and neutralizingpancreatic enzymes.3

In the past, several trials in which the investigators usedgrowth factor (insulin-like growth factor-1) or growth hor-mone directly (somatotropin) were focused on the goal ofaccelerating intestinal growth; supplementation with gluta-mine to provide optimal intestinal physiology also wasused with no objective positive results. Recently, the use ofan analog to a naturally occurring gastrointestinal hormone(glucagon-like peptide-2-2) has emerged but has not beenused in children. This agent is known to play a role in pro-moting adaptation by increasing villous height and cryptdepth and by altering enterocyte turnover, thus increasingabsorptive surface.The surgical options for therapy have evolved and have

had a major impact on adaptation. Such approaches rangefrom the simple establishment of continuity of the bowel,when multiple atretic segments occur or when the bowelhas been divided because of major discrepancies in diameter,to re-establishment of continuity between the small and largebowel to optimize absorption of water and electrolytes as well

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THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. -, No. -

as other nutritional factors, such as short-chain fatty acids,particularly if the ileo-cecal valve is present and intact. Othertypes of autologous reconstruction aimed at decreasing thevelocity or rapidity of the intestinal transit by either creating“valves” by intussuscepting segments of bowel or by trying toreverse the peristalsis by interposing segments of retro-peristaltic colon were found to be nonefficacious and havebeen abandoned. Other procedures aimed at decreasing thedilation of the small intestine, either by longitudinally resect-ing a portion of the antimesenteric side of the dilated smallbowel or by imbricating the bowel to reduce its diameter,have been performed at many institutions and proclaimedto be efficacious.

Other types of surgical techniques, some quite ingeniousbut perhaps based on our simplistic mechanical view or beliefin the concept that longer length facilitates better absorption,have led to the development of procedures determined tolengthen the bowel. In the Bianchi procedure, the intestineis divided longitudinally along the mesenteric axis, preser-ving the vasculature, creating two lumens with use of a staplerand then suturing pieces in continuity thus doubling thelength of the segment.

More recently, a procedure involving a series of transverseincision (serial transverse enteroplasty) with a staplerdecreased the width (and the surface) but increased thelength of the dilated bowel while destroying at least someof the vasculature and normal circulation, the anatomicalarray of the longitudinal and circular muscle layers, and thearrangement of the intrinsic nervous system, rendering thesegment nonmotile. All these techniques have had variableand sometimes opposite results in different studies, andsome of the small series presented as favorable are difficultto analyze; adaptation probably was already on the way orachieved and a thorough and critical analysis of the resultshas not taken place.

The growth variables in these studies, the amount of stooloutput, as well as the claim for “adaptation” achieved is vagueto modest at best. In our experience, with a few cases surgi-cally managed in our institution and the majority in whichsurgery was performed elsewhere in patients referred subse-quently for transplantation, poor results were usuallyobserved, particularly among those with ultra-short boweland/or those with remaining bowel that already may havehad marginal motility, because of dilation, ischemia, severewall thickening, or because of being very adherent.4-8

One aspect usually not found or addressed in the currentliterature on this subject is the descriptive pathology ofsegments that have undergone previous revisions or length-ening because often they are found to be narrowed, con-tracted, and scarred (sometimes replaced by prominentfibrous tissue with subsequent narrowing and further dila-tion of the proximal intestine) at the time of transplantation,usually undertaken because the patient has failed to adapt.

In the current series, patients who had undergone length-ening procedures more frequently were in the group whofailed to adapt. This consideration is important in patientswith ultra-short small bowel. The small number of patients

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in the current series, as stated by the authors, decreases thestatistical power, but it is interesting to note that the surgeonsdescribe dilations of the bowel proximal or distal to even theportion upon which the procedure was performed, suggest-ing that the consequence on transit in that area of intestineis in practical terms obstructive.Another recent addition to surgical therapies has been

organ transplantation; different types of grafts and surgicaltechniques have been developed, including liver transplant,the use of an isolated segment of small bowel, or the use ofseveral organs including liver, pancreas, and even segmentsof colon. For intestinal grafts, the results are not encouragingto date, even with major advances in the field of immunosup-pressant agents and medications, which have improved theshort term or first-year survival rates of patients and grafts,although not affecting a fairly mediocre long-term graftsurvival rate. It seems that the bowel, because it is the largestimmunologically active organ, is also the most difficult to“tame” with immunosuppressive medications. It requiresnot only larger doses or greater levels of some commonlyused agents but also a combination of several drugs simulta-neously, which often leads to infectious complications as wellas a high incidence of lymphoproliferative disorders, and stillnot producing normal growth or nutritional independenceand autonomy.The decision to offer only transplantation of the liver in the

case of severe liver failure, specifically in patients with shortgut syndromes, remains difficult and controversial becausethe rate of graft failure is greater for transplantation per-formed for other indications of end-stage liver disease; thedetermining factor may indeed be the lack of good graftperfusion in the case of short bowel syndrome. The mainindications for transplantation continue to be the presenceof severe liver disease and the lack of vascular access.Our understanding of what is now called parenteral nutri-

tion�associated (ie, intestinal failure�associated) liver dis-ease has evolved and importantly has linked the frequencyand type of infections of central venous catheters, certaintypes of metabolic imbalances in the diets provided, theadministration of “large” amounts of calories as fat, certaintypes of fatty acids, and the presence of deleterious chemicalsin the lipid emulsions exclusively derived from soy or soybased products. The reduced or limited use of these typesof emulsions and/or the substitution of fats with fish-oilderived, omega 3 fatty acids, has proven to be efficacious inpreventing as well as reversing cholestasis and inflammation.The use of enteral omega-3 fatty acids has had a beneficial ef-fect as well. Larger trials in this country are still underway, butalready there seems to be substantial evidence of clear benefitof this therapy.9-12

One aspect that still is unclear in this population ofpatients, more apparent in those with necrotizing enteroco-litis or mid-gut volvulus, is the impact of an acute ischemicinsult to the liver. Theoretically, this also applies to those pa-tients with developmental anomalies, during intrauterinevascular accidents at different but early stages of intestinaldevelopment that compromise the venous return of the

- 2013 EDITORIAL

intestine, mesenteric, and thus, portal. Even potential infec-tious or chemical agents may have caused atresia of segments,which in turn compromises the portal flow or may havecaused inflammation of the liver. This is suggested by thepresence of markers of liver dysfunction and specifically he-patocellular necrosis in some infants before intravenousnutrition is administered.

Another area of major impact on the prevention of liverdisease is the prevention of catheter-associated infections,particularly those due to gram-negative bacteria. A teamapproach to educating parents and caregivers in the properuse of catheters, the administration of the solutions, and gen-eral care of the stomas and tube sites is critical. In general,catheter-associated infections more commonly are the resultof contamination rather than bacterial translocation from theintestine. Aggressive treatment and prevention of potentialinfections by the use of ethanol- or antibiotic-containinglocks to cap the central venous catheters are important con-siderations. In our experience, however, the main factor inprevention has been maintaining a consistent and strict pro-tocol for catheter care, coupled with extensive and ongoingeducation of parents and caregivers (Wozniak et al, unpu-blisted data, 2013).

The systematic treatment of bacterial overgrowth in thesepatients has not been proved to have a definite impact onreduction of infections, but it seems to have positive resultsin the improvement of tolerance of feedings as well asdecreasing volume of diarrhea. Much is yet to be learnedabout the macrobiota of these patients to establish clear vari-ables of therapy and therapeutic agents for this specific pur-pose.2

Enteral administration of urso-deoxycholic acid for theprevention of liver disease is promising, but there is limitedknowledge of the kinetics of the medication in children, itsability to be absorbed in the different categories or “topog-raphy” of remaining bowel, and whether the effect of themedication depends on its absorption. It is unclear whetheruse of urso-deoxycholic acid, besides perhaps helping maxi-mize enteral feedings, changes the volume of diarrhea,changes composition of bile, improves biliary flow, and pre-vents or decreases cholestasis and thus cholelithiasis.

In general the evidence base for medical and nutritional in-terventions in the context of intestinal failure in children islimited. The major lesson of the current series is that poten-tially better outcomes for these patients depend on earlyintervention and referral to the multidisciplinary intestinalfailure center. Benefits include enhanced survival rate,improved overall quality of life, and the capacity to achieveadaptation and become independent of the IV calories.Cooperation and communication among these larger centers

hopefully will bring improvement in evidence-based man-agement, through larger and better cohort and case-controlresearch. n

Jorge H. Vargas, MDDivision of GastroenterologyHepatology, and NutritionDepartment of Pediatrics

Geffen-UCLA School of MedicineLos Angeles, California

Reprint requests: Jorge H. Vargas, MD, Division of Gastroenterology,

Hepatology & Nutrition, Department of Pediatrics, Geffen-UCLA School of

Medicine, Los Angeles, CA 90095-1752. E-mail: jvargas@mednet.ucla.edu

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