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Management of intestinal failure
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     Department of Child Health, King's College Hospital, London, United Kingdom

    Abstract

    Intestinal failure (IF) occurs when the body is unable to sustain its energy and fluid requirements without support, due to loss of functional small bowel. Prolonged IF is seen after large intestinal resection and described as short bowel syndrome (SBS). The hallmark of the management is parental nutrition (PN), which is costly and may be associated with the well-recognized problems of parental nutrition associated liver disease (PNALD) and line related sepsis. Cessation of PN at the earliest possible stage is desirable but for this enteral autonomy has to be achieved first. Intestinal adaptation occurs when the remaining gut goes through morphological changes increasing its absorptive capacity. Factors such as intraluminal nutrients, gastrointestinal secretions and hormones facilitate adaptation. Enteral feeds are a potent stimulant to adaptation, and should be started as soon as the clinical situation permits. Some drugs are thought to increase intestinal adaptation. These include glutamine, growth hormone and glucagon like peptide- 2, but there is a paucity of pediatric data to guide their use. In some cases surgical bowel lengthening procedures can be performed to increase the absorptive surface area. An isolated liver transplantation may be required if the liver has sustained irreversible damage but intestinal autonomy seems achievable. When prolonged PN is either unsustainable or associated with unacceptable side effects, small bowel transplantation should be considered as a treatment option.

    Keywords: Intestinal failure; Short bowel syndrome; Intestinal adaptation; Parenteral nutrition

    Intestinal failure (IF) is defined as the reduction of functional small bowel mass and absorptive surface area below a minimum needed for absorption of nutrients and fluids to maintain baseline energy requirements, fluid requirements and electrolyte homeostasis. In simpler terms it is the inability to maintain nutritional and fluid balance without support. A transient and usually reversible form of IF is commonly seen in gastroenteritis. Infective diarrhea is the commonest form of IF in the developing world. A variety of diseases cause prolonged IF and despite different pathophysiology they have a requirement for treatment with parenteral nutrition (PN) in common.

    Causes for prolonged IF are large intestinal resection, congenital enterocyte abnormalities such as microvillous inclusion disease and gastrointestinal motility disorders such as long segment Hirschsprung's disease or intestinal pseudo-obstruction syndrome.[1] The entity of IF after intestinal resection is referred to as short bowel syndrome (SBS). The underlying processes leading to intestinal resection are many. These include antenatal problems such as intestinal atresias, abdominal wall defects such as gastroschisis, malrotation and volvulus and necrotizing enterocolitis (NEC) in the neonatal period, predominantly in premature infants.

    There are different definitions of SBS. Some are based on the need for intervention, for example PN dependency for more than 1- 3 months post resection. Other definitions are based on residual bowel length. For instance, a residual small bowel length of less than 25% of the expected for age and gestation is considered as SBS.[2] A working group studying Canadian neonatal units has estimated the incidence of SBS as 1 per 4000 live births and the mortality rate as 37.5 %.[3] The major predictors for mortality are PN associated liver disease and length of remaining small intestine.[4] The aim in the management of IF is to achieve intestinal autonomy. For this the gut remnant undergoes changes to compensate for the loss of absorptive surface area known as intestinal adaptation. Positive predicting factors of achieving intestinal autonomy and successfully weaning PN are generally said to be the age- adjusted percentage of the remaining small bowel and the presence of the ileocecal valve (ICV).

    Intestinal physiology and adaptation in SBS

    The small bowel length of a healthy neonate is 200- 250 cm. Due to the variation in individual small bowel length it is important to measure the residual small bowel after intestinal resection rather than the length of resected bowel. The jejunum constitutes 40% of the small intestine. The greatest nutrient absorption takes place in the jejunum. Due to the higher nutrient concentration the size of the villi is larger which increases the absorptive area. Vit B12 and bile salt absorption takes place in the ileum exclusively. The ileum promotes sodium absorption regulated by aldosterone. Many gastrointestinal hormones are derived from the ileum. Large ileal resection leads to hypergastrinaemia and increased secretions as negative feedback mechanisms as gastrin secretion is lost due to lack of enteroglucagon . The colon absorbs water and electrolytes and thickens the faeces. The ileocecal valve (ICV) separates the terminal ileum from the large bowel. It regulates the exit of fluid and nutrients into large bowel and acts as a mechanical barrier preventing colonic bacteria from colonizing the small bowel. In general a preserved ICV is a positive predictor of achieving intestinal autonomy. Whether this is due to the ICV itself or a secondary effect due to preserved terminal ileum or colon is not clear. Patients after large intestinal resection often have rapid gastric emptying. This causes abnormally hypertonic intraluminal bowel contents. This causes an influx of water into the proximal small bowel. Patients with a high jejunostomy are therefore susceptible to large fluid losses.

    Intestinal adaptation takes place after bowel resection in which the remaining small bowel undergoes changes to meet the nutritional and fluid requirements. In the first few days post extensive gut resection, the remaining enterocytes make functional changes and express more membrane bound transporters to increase the absorptive capacity. The next step is a structural change to increase the absorptive surface area. The whole intestinal mass increases by hyperplasia, a proliferative epithelium develops increasing the crypt size. The cell cycle time is decreased and the cell production rate is increased. The villi also undergoes morphological changes and increase in height. The hyperplastic epithelium shows initially functional immaturity. As a consequence of the enterocyte hyperplasia the intestine grows in length. An increased folding is seen increasing the surface area causing dilatation of the small bowel. Gut motility is decreased to allow an increased nutrient contact time to the brush border maximizing absorptive efficacy. Enteral nutrition has a very important role in intestinal adaptation. Patients with exclusive PN develop small bowel mucosal atrophy. Intraluminal contact of nutrients with the enterocyte is essential for the process of adaptation. Nutrient sensitive epithelial proliferation is caused by direct stimulation with nutrients acting as 'fuel' for the enterocyte. Functional stimulation by activating paracrine mechanisms is of even greater importance. Nutrients also stimulate the secretion of hormones and pancreatic digestive secretions, which are involved in stimulating the adaptation process itself.[5]

    Management of IF

    Enteral nutrition (EN)

    The introduction of enteral nutrition (EN) at an early stage is a key factor in achieving intestinal autonomy. This cannot be overemphasized, as EN is essential to stimulate and enhance the adaptive processes of the remaining gut. Malabsorption due to the reduction of absorptive surface area is inevitable and excessive nutrients cause an osmotic load resulting in diarrhea. Unabsorbed nutrients can also be fermented by the intestinal bacterial flora causing clinical symptoms of distension, bloating and promoting bacterial overgrowth.

    Giving EN in a continuous fashion using nasogastric feeding tubes or gastrostomies has the advantage of constant enterocyte stimulation and avoids osmotic overload compared to bolus feeds. To prevent subsequent feeding problems oral stimulation should be started at an early stage. Oral feeds, fluid and solids, should be introduced at a clinically permissible stage.

    There is a paucity of prospective human studies regarding the most effective type of enteral diet. Certain specific luminal nutrients and the complexity of the diet are known to be important factors stimulating adaptation.

    It is generally thought that amino acids are very well tolerated as they are more rapidly absorbed and have a lower residue, and are the enteral protein source most commonly used in our institution. However, it has been suggested that they provoke less paracrine stimulation at enterocyte level and therefore delay adaptation in comparison to a diet containing peptides or protein.

    An impaired fat absorption may be seen due to pancreatic insufficiency and bile salt pool depletion as the entero- hepatic circulation is interrupted. Medium chain triglycerides (MCT) are directly absorbed by the enterocyte and do not require pancreatic enzymes or bile salts. MCT however promote enterocyte proliferation to a lesser content than long chain triglycerides (LCT).

    Complex carbohydrates decrease osmotic load and improve adaptation process, but may be less readily absorbed.

    Soluble fiber such as Pectin 0 slows gastric emptying. In the colon it is fermented to short chain fatty acids (SCFA) by bacteria. SCFA are absorbed in the colon and provide an additional energy source. They also promote water and sodium absorption in the colon. Fiber stimulates adaptation but may not be useful in patients with an absent colon.

    Biochemical parameters

    Close monitoring of serum electrolytes, renal and liver function renal is essential to monitor dehydration, electrolyte disturbances and evolving liver dysfunction. Hyponatremia can cause growth failure and potassium disturbances can lead to cardiac arrhythmias. Serum sodium levels may not reflect total sodium depletion. Measuring urine electrolytes can be helpful in estimating these requirements.

    Liver function tests need to be closely monitored to look for evidence of evolving cholestasis secondary to PN. Full blood counts give information regarding anemia and inflammation. Serum lipid levels, glucose, fat soluble vitamins and trace elements such as copper, zinc and selenium should be monitored. In comparison to hepatic or renal failure no biochemical marker exists to exclusively monitor the severity and progress of intestinal failure. Citrulline has been found to be a useful marker of functional absorptive bowel length. It is an amino acid that is not incorporated into protein and it is exclusively produced by the intestinal mucosa. Rhoads et al have studied the pediatric SBS population and shown that patients with SBS have lower citrulline levels. In a study of 24 infants with SBS they demonstrated a linear relationship between serum citrulline levels and the percentage of tolerated enteral calories. They have postulated that a citrulline level 3 19 mmol/L is a positive predictive marker of achieving enteral autonomy and is therefore a useful indicator in children with SBS.[6]

    Pharmacological treatment

    There are two different strategies in the pharmacological treatment of IF. One is to treat symptoms, the other being to specifically optimize intestinal adaptation. The later is currently still in an experimental phase but will certainly play a more prominent role in future. Proton pump inhibitors or H 2 - receptor antagonists are useful in treating hypergastrinaemia and hypersecretion occurring after intestinal resection. Antidiarrheals decrease motility and whole transit time and are sometimes used if the stool output is increased. They should be used with caution as they can cause stasis in particular in dilated bowel loops and promote bacterial overgrowth. Octreotide, a somatostatin analogue, can theoretically control high output stoma losses but it impairs the intestinal adaptation process and side effects limit its use in this setting.

    Drugs affecting intestinal adaptation

    Glutamine

    Glutamine acts as a direct fuel for enterocytes and stimulates mucosal cell proliferation. Glutamine given parenterally to patients on total PN stabilizes the mucosal structure, preventing mucosal atrophy and decreasing gut permeability.[7]

    In their practice the author routinely use glutamine enterally but currently little evidence exists supporting this practice.

    Growth Hormone (GH)

    GH stimulates adaptation and has a positive effect on nutrient absorption. It has insulin- like growth factor 1 (IGF-1) mediated mitogenic effects on the crypts stimulating small bowel growth and increasing colonic mass. These effects have been demonstrated in a murine model.[8] Human studies have been somehow inconclusive and no pediatric data is available. A recent study in adults is however promising. Byrne et al demonstrated, in a double-blinded randomized control trial involving 40 patients, that the group receiving GH had significantly higher reduction in PN requirements. They postulate that GH aids intestinal compensation and that GH might play an important role in the future treatment of IF. Intermittent treatment cycles in combination with glutamine may be a possibility.[9]

    0 Glucagon- like peptide 2 (GLP-2)

    Glucagon- like peptide 2 (GLP-2) is a hormone excreted by the L- cells of the distal ileum and colon as response to intraluminal nutrients. It promotes intestinal adaptation by decreasing gastric emptying, motility and secretion and increasing the absorptive capacity by promoting epithelial proliferation. The epithelial barrier function increases and the enterocyte develops resistance to apoptotic injury.[10] Serum GLP-2 levels are significantly diminished in infants with intestinal failure.[11] Pilot studies have demonstrated that GLP-2 or its analogues has an intestinotrophic effect when given to adult SBS patients.[12],[13] No prospective pediatric studies using GLP-2 as a treatment have been conducted yet, but it is possible that it may be of importance in the treatment of IF in future.

    Complications of IF management

    Venous catheter related problems

    Parental nutrition is significantly associated with morbidity and mortality. Line related problems commonly occur. Local and systemic infections of lines occur some times leading to life threatening sepsis. Mechanical damage and blockage can occur in particular due to the precipitation of calcium and phosphate salts from the PN solution. Thrombosis of the vessels can occur. It is essential to prevent line infection by handling central lines in an aseptic matter using a non-touching technique. Advances in venous catheters have been made, catheters impregnated with antimicrobial agents are available. Also the use of a silver impregnated cuff reduces bacterial colonization. Antiseptic hubs are available, the use of regular antibiotic locks or prophylactic anticoagulation are another option.[14]

    Small Bowel Bacterial Overgrowth (SBBO)

    As part of the adaptation process the small bowel remnant dilates and the motility is reduced. The combination of reduced antegrade peristalsis and reduced mucosal immunity provides an excellent ground for bacterial colonization. The ICV acts as a mechanical barrier and there is a potential disadvantage if the valve is missing. The bacteria deconjugate intraluminal bile salts. This causes bile salt pool depletion and impaired micellar solubilisation. The consequence is steatorrhoea. Fat-soluble vitamin deficiency is another problem. The deconjugated metabolites get reabsorbed and are hepatotoxic. The presence of colonic gut flora in the small bowel causes mucosal inflammation. The symptoms of SBBO are manifested as mild abdominal distention and discomfort, bloating, cramps, flatulence and diarrhea. Rarely patients can develop life threatening D- lactic acidosis due to bacterial fermentation of carbohydrates.[15] The diagnosis can be made by hydrogen breath test. The gold standard, however, is the endoscopic sampling of intestinal fluid and microbiologic culture.

    Antibiotics are used to decrease bacterial replication. These are targeted against anaerobes and facultative anaerobes. To prevent the development of resistant strains multiple antibiotics can be given in a cyclic fashion. Metronidazole is commonly used. Oral aminoglycosides such as gentamicin can also be used. As they have a very poor enteral absorption, systemic side effects are minimal. In the author's unit ciprofloxacin is used in rotation with the other previously mentioned antibiotics in a cyclical fashion with good results. Probiotics might play a therapeutic role by competing with the colonic bacteria, however, clinical trials are needed to evaluate this.[16] In cases of severe dilatation surgical procedures such as bowel tapering or lengthening procedures are helpful.[2]

    Parental Nutrition Associated Liver Disease (PNALD)

    Patients receiving parental nutrition (PN) are at risk of developing cholestasis known as PNALD. The duration of PN administration is directly linked with the development of PNALD. The exact etiology is unknown but it is thought to be of multifactorial origin. Lack of enteral feeding reduces the secretion of hormones in particular cholecystokinin (CCK). This impairs gallbladder emptying, bile secretion and bile flow. Bile acid synthesis is impaired in the infant liver and bile acid reabsorption reduced due to the disrupted entero-hepatic circulation. The small intestine is prone to bacterial overgrowth. Bacteria deconjugate bile salts in the bowel lumen and produce potential hepatotoxic metabolites. Sepsis is thought to play a major role in particular in extensive bowel resection due to the loss of gut associated lymphoid tissue. Impaired gut mucosal barrier function promotes bacterial translocation and portal bacteremia. Bacterial lipopolysaccharides and endotoxins activate cytokine pathways causing inflammation of the liver.[17] The PN solution itself can be damaging if it is not tailored to the individual needs. Certain amino acids have been linked with hepatotoxicity such as methionine and cystine. In the animal model taurine deficiency has been associated with PNALD. It is unclear if this is due to bile acid conjugation or antioxidative, membrane stabilizing effects.[18] Excessive use of lipid emulsions is thought to be hepatotoxic. Exact mechanisms are unclear. One theory is the accumulation of hepatotoxic phytosterols, another is that lipids increase the production of pro-inflammatory cytokine precursors.

    There is a controversy regarding the cessation of lipids in PNALD: lipids provide a substantial amount of calories, substituting this by carbohydrate load promotes hyperinsulinism and hepatic steatosis. Conscientious use is essential and in author's experience lipid may be cautiously given in a cyclical fashion even in progressive cholestasis. There are, however some studies describing resolution of PNALD by cessation of the lipid component.[19]

    Progressive cholestasis leads to liver failure. Malabsorption is increased due to several factors such as reduced bile flow with luminal bile acid deficiency and portal hypertension with porto- systemic shunting causing bowel wall edema, exudative enteropathy and hemorrhage. In advanced PNALD often the only therapeutic option is liver transplantation as an isolated procedure or in combination with a small bowel transplant (SBT). Currently best practice to prevent PNALD includes the promotion of early enteral feeds, prevention of sepsis and SBBO, and aggressive weaning from PN. Improvement in PNALD may precipitate a reduction in enteral calorie requirements. If there is evidence of cholestasis ursodeoxycholic acid (UDCA) should be commenced. In practice all patients with long term IF should be on UDCA. Some data is available suggesting that giving CCK reduces serum bilirubin levels and is beneficial in PNALD.[20] In author's department is selectively used CCK but multi center studies would be desirable to support evidence of this practice.

    Surgical management

    Patients with prolonged PN dependency may benefit from surgical procedures to increase small bowel length and absorptive surface area. Tapering enteroplasty and the Bianchi longitudinal intestinal lengthening procedure may be performed. Dilated bowel loops decrease motility and increase absorptive surface area but can become pathologic causing nutrient stasis and promoting SBBO. These dilated loops of bowel are commonly detected by contrast radiographical studies such as a barium follow through procedure, which should be routinely performed in the assessment of children with prolonged IF. To preserve the intestinal length a tapering enteroplasty can be performed rather than resecting the dilated bowel segment. The Bianchi procedure involves dividing a dilated bowel segment longitudinally and thereby creating two new bowel segments which are end- to- end anastomosed. Other procedures are available such as the serial transverse enteroplasty (STEP) first described in 2003. This procedure does not require bowel anastomosis and can theoretically increase the intestinal length more than double compared to the Bianchi procedure.[2]

    Transplantation

    In irreversible failure small bowel transplantation (SBT) is a therapeutic option. The indications are mainly complications of long-term of PN administration such as progressive PNALD, recurrent life threatening septic events and the lack of venous access due to thrombosis of the major vessels by previous central venous catheters. Compared to other solid organ transplantation one major challenge is the large lymphoid tissue mass of the graft and the intraluminal colonization of multiple bacteria. With the introduction of new immuno- suppressive agents the long-term survival rate is improving. The Paris pediatric intestinal transplant team has recently published their experience over the last 10 years: 126 pediatric patients underwent SBT with a three-year survival rate of 71.5 %. All patients have achieved nutritional autonomy and PN has been completely discontinued.[21] It will be interesting to see the 5 and 10 year survival data and to see what effect the complications of long term relatively high dose immunosuppresion such as post- transplant lymphoproliterative disease have on the morbidity and mortality. Compared to the relatively new procedure of SBT a larger experience exists in isolated liver transplantation. The advantage compared to a combined liver and small bowel transplant is the better organ availability especially as well-established organ reduction techniques are available. It requires less immuno-suppression compared to a small bowel graft and currently has better survival rates.[22] Therefore, if it is likely that intestinal autonomy can be achieved despite end stage PNALD an isolated liver transplantation should be performed. PN remains the primary therapy in prolonged IF, with excellent rates of survival reported by many centers, but given the recent advances it is likely that SBT will become an alternative as primary treatment in the future.

    Conclusion

    Prolonged intestinal failure after intestinal resection is a common problem occurring with a frequency of 1 in 2000 NICU admissions.[3] Parental nutrition is the mainstay of medical management. This treatment, however, has risks and cost implications. The aim is to wean PN as aggressively as possible and to achieve enteral autonomy. Compared to adult SBS the pediatric patients not only have to meet their baseline energy requirements but also need to be provided with additional energy and nutrients to sustain growth. After large intestinal resection the remaining intestine goes through complex changes to increase nutrient absorptive surface area such as epithelial hyperplasia, increased villus length and crypt depth and bowel dilatation. This process is known as intestinal adaptation. Several stimulants facilitate adaptation mainly enteral nutrients, GI hormones and growth factors.

    Current best practice promoting intestinal adaptation is the early start of enteral feeding. Enteral feeding regimens have to be tailored to the patient's specific needs, multiple factors influence this such as total length of the intestinal remnant, the absence of the colon, pancreatic insufficiency and liver disease. Prospective multi centre studies are required investigating the most beneficial feeding regimen, evidence based guidelines are needed. The management of IF patients is complex and involves a multidisciplinary team including a paediatric gastroenterologists and pediatric surgeons, specialist nurses, dieticians, pharmacist, speech and language therapist, biochemists and microbiologist. If enteral autonomy cannot be achieved during hospital admission the patient can sometimes receive PN at home. Currently various groups are studying pharmacological agents that promote intestinal adaptation. Glutamine, growth hormone and the intestinal hormone GLP-2 are shown to have intestinotrophic effects. The majority of the studies are derived from animal models or from adult populations. More prospective pediatric studies are needed to establish treatment protocols maximizing efficacy and minimizing side effects. In future these adaptation modulating drugs may play a significant role in the medical management.

    Surgical bowel lengthening is another way of increasing the absorption surface area. This currently requires dilated loops of bowel, which should be identified by contrast studies. New techniques such as the STEP procedure appear to be more efficient than conventional bowel lengthening methods such as the Bianchi procedure and may hold promise for future management.

    Long term complications of IF are mainly due to the prolonged administration of PN. Venous catheter related sepsis occurs and can be life threatening. Sepsis is often promoted by bacterial translocation from the intestine into the portal-venous system. Central lines have to be accessed in a sterile manner; new products such as silver coated or antimicrobial impregnated venous catheters are available. Small bowel bacterial overgrowth needs to be treated and prevented as it causes increased malabsorption, bacterial translocation and unwanted clinical symptoms.

    PN associated liver disease (PNALD) is a strong positive predicting factor of mortality in IF. The exact etiology is unknown but several factors are contributory such as inflammation due to portal bacteremia, septic episodes and the PN solution itself. The liver undergoes fibrotic changes and cirrhosis can occur. Often liver transplantation is needed as an isolated procedure or in combination with an intestinal transplantation. The best way to prevent PNALD is the cessation of PN.

    Intestinal transplant is relatively new procedure. Transplanting small bowel has the challenge of implanting a large lymphoid tissue mass and intraluminal bacteria. A higher dose of immunosuppresion compared to other solid organ transplantation is needed. With the introduction of new immuno- modulating agents and an increasing experience however, survival rates are now improving.

    Acknowledgements

    We would like to thank K Maxwell, pediatric gastroenterology dietician for her help with the enteral feeding section.

    References

    1. Goulet O, Ruemmele F, Lacaille F, Colomb V. Irreversible intestinal failure. J Pediatr Gastroenterol Nutr 2004; 38(3) : 250-269.

    2. Wales PW. Surgical therapy for short bowel syndrome. Pediatr Surg Int 2004; 20(9) : 647-657.

    3. Wales PW, de Silva N, Kim J, Lecce L, To T, Moore A. Neonatal short bowel syndrome: population-based estimates of incidence and mortality rates. J Pediatr Surg 2004; 39(5): 690-695.

    4. Spencer AU, Neaga A, West B, Safran J, Brown P, Btaiche I et al. Pediatric short bowel syndrome: redefining predictors of success. Ann Surg 2005; 242(3) : 403-409.

    5. DiBaise JK, Young RJ, Vanderhoof JA. Intestinal rehabilitation and the short bowel syndrome: part 1. Am J Gastroenterol 2004; 99(7) : 1386-1395.

    6. Rhoads JM, Plunkett E, Galanko J, Lichtman S, Taylor L, Maynor A et al. Serum citrulline levels correlate with enteral tolerance and bowel length in infants with short bowel syndrome. J Pediatr 2005; 146(4) : 542-547.

    7. van der Hulst RR, van Kreel BK, von Meyenfeldt MF, Brummer RJ, Arends JW, Deutz NE et al. Glutamine and the preservation of gut integrity. Lancet 1993; 341(8857) : 1363-1365.

    8. Shulman DI, Hu CS, Duckett G, Lavallee-Grey M. Effects of short-term growth hormone therapy in rats undergoing 75% small intestinal resection. J Pediatr Gastroenterol Nutr 1992; 14(1): 3-11.

    9. Byrne TA, Wilmore DW, Iyer K, DiBaise J, Clancy K, Robinson MK et al. Growth hormone, glutamine, and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome: a prospective, randomized, placebo-controlled, double-blind clinical trial. Ann Surg 2005; 242(5) : 655-661.

    10. Drucker DJ. Gut adaptation and the glucagon-like peptides. Gut 2002; 50(3) : 428-435.

    11. Sigalet DL, Martin G, Meddings J, Hartman B, Holst JJ. GLP-2 levels in infants with intestinal dysfunction. Pediatr Res 2004; 56(3) : 371-376.

    12. Jeppesen PB, Sanguinetti EL, Buchman A, Howard L, Scolapio JS, Ziegler TR et al. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut 2005; 54(9) : 1224-1231.

    13. Jeppesen PB, Hartmann B, Thulesen J, Graff J, Lohmann J, Hansen BS et al. Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon. Gastroenterology 2001; 120(4) : 806-815.

    14. Cicalini S, Palmieri F, Petrosillo N. Clinical review: new technologies for prevention of intravascular catheter-related infections. Crit Care 2004; 8(3) : 157-162.

    15. Zhang DL, Jiang ZW, Jiang J, Cao B, Li JS. D-lactic acidosis secondary to short bowel syndrome. Postgrad Med J 2003; 79(928) : 110-112.

    16. Vanderhoof JA, Young RJ, Murray N, Kaufman SS. Treatment strategies for small bowel bacterial overgrowth in short bowel syndrome. J Pediatr Gastroenterol Nutr 1998; 27(2) : 155-160.

    17. Kaufman SS. Prevention of parenteral nutrition-associated liver disease in children. Pediatr Transplant 2002; 6(1) : 37-42.

    18. Moran JM, Salas J, Botello F, Macia E, Climent V. Taurine and cholestasis associated to TPN. Experimental study in rabbit model. Pediatr Surg Int 2005; 21(10) : 786-792.

    19. Colomb V, Jobert-Giraud A, Lacaille F, Goulet O, Fournet JC, Ricour C. Role of lipid emulsions in cholestasis associated with long-term parenteral nutrition in children. JPEN J Parenter Enteral Nutr 2000; 24(6) : 345-350.

    20. Teitelbaum DH, Han-Markey T, Schumacher RE. Treatment of parenteral nutrition-associated cholestasis with cholecystokinin-octapeptide. J Pediatr Surg 1995; 30(7) : 1082 1085.

    21. Goulet O, Sauvat F, Ruemmele F, Caldari D, Damotte D, Cezard JP et al. Results of the Paris program: ten years of pediatric intestinal transplantation. Transplant Proc 2005; 37(4):1667-1670.

    22. Horslen SP, Sudan DL, Iyer KR, Kaufman SS, Iverson AK, Fox IJ et al. Isolated liver transplantation in infants with end-stage liver disease associated with short bowel syndrome. Ann Surg 2002; 235(3) : 435-439.(Soondrum K, Hinds R)