HPE HPE 85 – Spring 2017 - Page 49

Practical therapeutics Issue 85 | Spring 2017 longitudinally and then joining the two smaller lumens end-to-end to increase intestinal length and halve the diameter. Serial transverse enteroplasty (STEP) is a procedure where an endoscopic surgical stapler is applied to alternate sides along the length of the dilated intestinal segment to create a ‘zig-zag’ – a longer and narrower channel. Recurrent dilation of the bowel can occur after both procedures. However, unlike STEP, the LILT procedure can only be performed once. Although, these surgical procedures may not lead to enteral autonomy, they may have a role in certain individuals with dilated small bowel and limited enteral feed tolerance. Key points • Short bowel syndrome (SBS) is the most common cause of intestinal failure (IF) in children. • Provision of optimal nutritional support is essential during the period of intestinal adaptation. • Catheter-related blood stream infections and IF-associated liver disease are frequent complications related to parenteral nutrition. • Some children may benefit from bowel lengthening surgical procedures or intestinal transplantation. • Studies investigating the use of peptides in the treatment of SBS are ongoing. Transplantation Intestinal transplantation is indicated in children with irreversible IF who have recurrent life-threatening CRBSIs, IFALD or loss of vascular access. Patients with mild liver disease are offered isolated intestinal transplantation. However, combined liver and small bowel transplantation is recommended in those with severe IFALD. Isolated liver transplantation is indicated in children with SBS who are unable to achieve intestinal adaptation and enteral autonomy due to end-stage liver disease, provided they have previously tolerated at least 50% of their estimated daily calorie requirements enterally with adequate weight gain. 4,10 The criteria of some transplant centres includes a requirement of at least 30cm of functional small bowel, with or without the ileocecal valve, for this type of transplant. 4 Data from the two UK paediatric intestinal transplant centres report one-year survival of 85% and five-year survival of 60%. 12 Worldwide survival rates have been reported as 76%, 56% and 43% at one, five and ten years, respectively, which includes both adult and paediatric patients. 13 Participants either received teduglutide 0.0125mg/kg/day (n=8), 0.025mg/kg/ day (n=14), 0.05mg/kg/day (n=15), or standard of care (n=5). Patients in the teduglutide group required PN on seven days of the week at baseline. Four patients were weaned off PN by week 12 in the teduglutide group (0.05mg/kg, n=3; 0.025mg/kg, n=1), and two of these patients restarted PN after a four-week wash-out period. The greatest reduction in mean prescribed PN volume was seen in the 0.05mg/kg and 0.025mg/kg teduglutide groups. Improvement in enteral nutrition was seen in all four groups, and was maintained after teduglutide was discontinued. Teduglutide has recently been approved for use in the EU for children with SBS aged one year and above, administered as a subcutaneous injection at a dose of 0.05mg/kg once daily. The cost of 28 vials (5mg strength) is approximately £15,000. A double-blind, controlled trial is currently being conducted in children with SBS who are PN-dependent. 16 They are randomised to subcutaneous teduglutide 0.05 or 0.025mg/kg/day, or standard of care for 24 weeks. The primary outcome measures are safety and tolerability of teduglutide treatment, and at least 20% reduction in PN volume from baseline. The estimated completion date of this study is June 2017. Emerging treatment The naturally occurring human glucagon- like peptide-2 (GLP-2) is secreted by L-cells of the intestine. Teduglutide is an analogue of GLP-2 and a designated orphan drug. In non-clinical studies, it has been shown to increase villous height and crypt depth, 14 thereby increasing the intestinal absorptive surface area. Carter et al 15 conducted a 12-week open-label study that included 42 patients aged 1–17 years with SBS and who were PN- dependent for at least one year. Conclusions In the future, tissue engineering may provide further treatment options in children with SBS. However, current management of these patients can be optimised with a multidisciplinary approach to promote intestinal adaptation, maintain growth and development and prevent potentially life-threatening complications. The ultimate goal is to achieve enteral autonomy and improve the overall quality of lives of these children and their families. References 1 Duro D et al. Overview of paediatric short bowel syndrome. J Paediatr Gastroenterol Nutr 2008;47:S33–S36. 2 Batra A, Beattie RM. Management of short bowel syndrome in infancy. Early Hum Dev 2013;89:899–904. 3 Sulkowski JP, Minneci PC. Management of short bowel syndrome. Pathophysiology 2014;21:111–8. 4 Gupte GL et al. Current issues in management of intestinal failure. Arch Dis Child 2006;91:259–64. 5 Goulet O et al. Neonatal short bowel syndrome as a model of intestinal failure: Physiological background for enteral feeding. Clin Nutr 2013;32:162–71. 6 D’Antiga L, Goulet O. Intestinal failure in children: The European view. J Paediatr Gastroenterol Nutr 2013;56(2):118–26. 7 Agostoni C et al. The need for nutrition support teams in paediatric units: A commentary by the ESPGH AN Committee on Nutrition. J Paediatr Gastroenterol Nutr 2005;41:8–11. 8 Koletzko B et al. Guidelines on paediatric parenteral nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr 2005;41(Suppl 2):S1–S87. 9 Chu H et al. Significant reduction in central venous catheter-related bloodstream infections in children on HPN after starting treatment with taurolidine line lock. J Pediatr Gastroenterol Nutr 2012;55(4):403–7. 10 Lacaille F et al. Intestinal failure-associated liver disease: A Position Paper of the ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation. J Pediatr Gastroenterol Nutr 2015;60(2):272–83. 11 Hojsak I et al. ESPGHAN Committee on Nutrition Position Paper. Intravenous lipid emulsions and risk of hepatotoxicity in infants and children: a systematic review and meta-analysis. J Pediatr Gastroenterol Nutr 2016;62(5):776–92. 12 Hogg R, Allen E. Annual report on intestine transplantation: Report for 2015/2016. NHS Blood and Transplant 2016. www.odt.nhs.uk/pdf/organ_specific_ report_intestine_2016.pdf (accessed March 2017). 13 Grant D et al. Intestinal Transplant Registry Report: Global activity and trends. Am J Transplant 2015;15:210–19. 14 Summary of Product Characteristics. Revestive. Shire Pharmaceuticals Limited. Last revised 10/2016. 15 Carter BA et al. Outcomes from a 12-week, open-label, multicentre clinical trial of teduglutide in paediatric short bowel syndrome. J Pediatr 2017;81:102–11e5. www.jpeds.com/article/ S0022-3476(16)31095-2/fulltext?rss=yes (accessed March 2017). 16 ClinicalTrials.gov. Short bowel syndrome research study for children up to 17 years of age on parenteral nutrition. www.clinicaltrials.gov/ct2/show/ NCT02682381 (accessed March 2017). 47 hospitalpharmacyeurope.com