SHORT BOWEL SYNDROME Wong Wui Bun Tuen Mun

SHORT BOWEL SYNDROME Wong Wui Bun Tuen Mun Hospital

Short bowel syndrome 1. Overview 2. Pathophysiology 3. Intestinal rehabilitation program 4. Medical treatment 5. Operative treatment 6. Transplantation

1. OVERVIEW Heterogeneous disease

1. Overview • Definition: • Malabsorptive state that is associated with extensive resection of small bowel as well as a range of congenital conditions (American College of Surgeons) • • • http: //www. nejm. org/na 101/home/literatum/publisher/mms/journals/content/nejm/2011/nejm_201 1. 364. issue-14/nejmicm 1001885/production/images/large/nejmicm 1001885_f 1. jpeg Heterogeneous group of patients Spectrum of disease severity Reduced survival (2 year 86%, 5 year 75%) Significant morbidity

1. Overview - causes Mesenteric ischaemia is the most common cause in adult

2. PATHOPHSIOLOGY Anatomy is the key

2. Pathophysiology • Fluid, electrolyte and nutritional deficiencies • Dysregulation of enteric hormone • Disturbance in bowel motility • Change in bowel flora • Catheter related complications • Intestinal failure related liver failure • Bone resorption, gallstone and renal stones

Effect of anatomy on pathophysiology Jejuno-ileal anastomtosis Jejunocolic anastomosis End jejunostomy Probability of PN dependence Low Increase if <35 cm Variable High if <60 -65 cm Variable High if <115 cm Pathophysiology Reduced CCK, Secretin Reduced gastrin clearance Loss of enterohepatic circulation of bile salt Vitamin B 12 deficiency Bacterial overgrowth Malabsorption No SCFA production Reduced GLP-1, GLP-2 and PYY Symptom Clinical problem Transient gastric hypersecretion and emptying Steatorrhoea Choleretic diarrhoea Fat malabsorption Cholestasis High stomal output Net fluid loss

Surgical considerations • Limit resection • Use of second look operation • Prevention of stoma/ early closure • Preservation of ileocaecal valve • Post-operative care • Early establishment of central venous assess • Early involvement of multi-disciplinary team

3. INTESTINAL REHAB Planned multidisciplinary care

3. Intestinal rehabilitation program • Multidisciplinary, protocolized care • Combination of enteric nutrition +/- hormonal stimulation • Workload hypothesis • Oral nutrition stimulate intestinal adaptation Morphological: Epithelial hyperplasia Increased villi height Increased crypt depth Remodeling of bowel Functional: Up-regulation of transport molecule and brush border activity http: //surgery. med. umich. edu/pediatric/chirp/clinical/mm/pathophysiology. shtml

3. Intestinal rehabilitation prgram • Systemic review 2013 by Stanger et. al. • Historical control (n=103) vs IRP (n=130) • Reduction in septic episodes (0. 3 vs. 0. 5 event/month; p=0. 01) • Increase in overall patient survival (22% to 42%) • Weaning from PN (RR=1. 05, 0. 88 -1. 25, p=0. 62) • Incidence of IFALD (RR=0. 2, 0 -17. 25, p=0. 48 • Relative risk of liver transplantation (3. 99, 0. 75 -21. 3, p=0. 11).

Enterotrophic hormone Growth hormone GLP-2 analog (Teduglutide) Short term use Long term use • Increase energy absorption • Gain in body weight • 20% reduction of parenteral support • Improved SBS-Qo. L scores Lack of good evidence Double blind RCT available • Metabolic complications • Acromegaly • Contraindicated in malignancy • Colonoscopic surveillance • Immunogenic

Intestinal failure Definition: Failure of intestine to adequately meet the body’s requirement for fluid, macronutrients and micronutrients Long term parenteral nutrition required • Predictors: • Bowel length <100 cm • End jejunostomy/ jejunocolic anastomosis • Reduced Citrulline level (<20 umol/L correlated with PN dependence)

4. MEDICAL TREATMENT Nutrition is backbone, what is more…

Medical treatment • Bacterial overgrowth • Increase parenteral nutrition requirement • D- lactic acidosis, mucositis, worsen diarrhoea • More common if ileocaecal valve absent • Empirical treatment with antibiotics

Medical treatment • Symptomatic care • Control of bowel motility and secretions • Lomotil, Imodium • Atropine • Proton pump inhibitor

5. OPERATIONS In selected patients

Autologus intestinal reconstruction • Indicated in intestinal failure with complications • Intestinal tapering • Longitudinal intestinal lengthening and tailoring (LILT) • Serial transverse enteroplasty (STEP) • Antiperistaltic segment • Colonic interposition

Choice of procedure • Preservation of absorptive surface • Dilated segment has impaired peristalsis • Technical difficulty • Feasibility of procedure: • Any bowel dilatation? • Any previous procedure? • Problem with transit time? • Antiperistaltic segment • Patient with a dilated bowel? • STEP/ LILT

Operative treatment - LILT

Operative treatment - STEP

Operative treatment LILT STEP Performed once Repeated procedure feasible Double length Variable increase in length Uniform dilatation Tailored diameter Dissection of mesentery No interference with blood supply Peritoneal contamination No contamination PN Dependence 45% PN Dependence 31 – 57% Transplant 18. 6% Transplant 4. 8 – 29%

Role of operation • Improve bowel autonomy • Decrease PN requirement • Decrease need for transplantation • Reverse liver disease up to 80% • Complications: • Intestinal obstruction • Anastomotic leakage • Bowel ischaemia • Mortality ~ 10%

6. TRANSPLANTATION Graft and patient survival problem

Transplantation • Intestinal transplant • Combined liver-intestinal transplant • Indications: • 1. Presence of PN-associated liver disease • 2. Loss of central venous access • 3. Recurrent catheter-related sepsis or a single episode of fungal sepsis • 4. Recurrent bouts of severe dehydration or metabolic abnormalities • (US Centers for Medicare and Medicaid Services) • ? Better catheter care • ? Improved parenteral nutrition • ? Quality of life • Early referral to specialist centre

Bring home message 1. Limit bowel resection 2. Early stoma closure 3. Intestinal rehabilitation program 4. STEP vs LILT 5. Considerations for transplant

Reference 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Modern treatment of short bowel syndrome. Jeppesen PB. Curr Opin Clin Nutr Metab Care. 2013 Sep; 16(5): 582 -7. doi: 10. 1097/MCO. 0 b 013 e 328363 bce 4. Review. Short bowel syndrome – surgical perspectives and outcomes. Nicola Smith, Rachel Harwood, Sarah Almond. Paediatrics and Child Health Volume 24, Issue 11, November 2014, Pages 513– 518 Serial transverse enteroplasty (STEP) for patients with short bowel syndrome (SBS). American College of Surgeons. Management of short bowel syndrome. Jason P. Sulkowskix. Jason P. Sulkowski. Pathophysiology. February 2014. Volume 21, Issue 1, Pages 111– 118 Surgical management of short bowel syndrome. Iyer KR 1. JPEN J Parenter Enteral Nutr. 2014 May; 38(1 Suppl): 53 S-59 S. doi: 10. 1177/0148607114529446. Epub 2014 Mar 25. Long-term outcome of short bowel syndrome in adult and pediatric patients. Wasa M 1, Takagi Y, Sando K, Harada T, Okada A. JPEN J Parenter Enteral Nutr. 1999 Sep-Oct; 23(5 Suppl): S 110 -2. Effect of growth hormone, glutamine, and enteral nutrition on intestinal adaptation in patients with short bowel syndrome. Guo M, Li Y, Li J. Turk J Gastroenterol. 2013; 24(6): 463 -8. Short bowel syndrome: highlights of patient management, quality of life, and survival. Kelly DG 1, Tappenden KA, Winkler MF. JPEN J Parenter Enteral Nutr. 2014 May; 38(4): 427 -37. doi: 10. 1177/0148607113512678. Epub 2013 Nov 18. Overview of short bowel syndrome: clinical features, pathophysiology, impact, and management. Storch KJ 1. JPEN J Parenter Enteral Nutr. 2014 May; 38(1 Suppl): 5 S-7 S. doi: 10. 1177/0148607114525805. Epub 2014 Mar 6. Pathophysiology of short bowel syndrome: considerations of resected and residual anatomy. Tappenden KA 1. JPEN J Parenter Enteral Nutr. 2014 May; 38(1 Suppl): 14 S-22 S. doi: 10. 1177/0148607113520005. Epub 2014 Feb 5. Teduglutide: A Review of its Use in the Treatment of Patients with Short Bowel Syndrome. Celeste B. Burness, Paul L. Mc. Cormack. Drugs. June 2013, Volume 73, Issue 9, pp 935 -947 Are plasma citrulline and glutamine biomarkers of intestinal absorptive function in patients with short bowel syndrome? Luo M 1, Fernández. Estívariz C, Manatunga AK, Bazargan N, Gu LH, Jones DP, Klapproth JM, Sitaraman SV, Leader LM, Galloway JR, Ziegler TR. JPEN J Parenter Enteral Nutr. 2007 Jan-Feb; 31(1): 1 -7. Intestinal dysbiosis in children with short bowel syndrome is associated with impaired outcome. Engstrand Lilja H, Wefer H, Nyström N, Finkel Y, Engstrand L. Microbiome. 2015 May 4; 3: 18. doi: 10. 1186/s 40168 -015 -0084 -7.

THANK YOU! Questions welcomed

Elemental diet • Peptamen • Vivomax • Monosaccharides • Disaccharides • Medium chain fatty acid • Amino acids • Vitamins • Minerals

Parenteral nutrition • >50% carbohydrates • 30 -40 % fat emulsion • Amino acids • Electrolytes • Additives: • Vitalipid: Vitamin A, D 2, E, K 1 • Soluvit: Vitamin C, Vitamin H, Vitamin Bs, folic acid • Addamel: trace elements

Options of venous access • Considerations: • Venous thrombosis rate per 1000 catheter day • Sepsis rate per 1000 catheter day • Reusability • Tunneled central venous access • Peripheral inserted central catheter (PICC) • Aseptic technique • 70% ethanol block • Heparin solution flush

Benefit of stoma closure • Recruit of distal bowel for adaptation • Resumption of enterohepatic circulation of bile salt • Production of short chain fatty acid (SCFA) in colon • Activation of L cell for enteric hormone production

Enteric hormone

Enteric hormones

STEP

STEP

SILT

Teduglutide

Transplantation Publication Results Pironi 2011 5 year survival: Not indicated for transplant: 87% (95%CI 83 -91%) Indicated but not transplanted 84% (95%CI 74 -94%) Indicated and transplanted 54% (95%CI 29 -79%) Mazariegos 2010 1 year in 1992 Graft survival 69% Patient survival 52% 1 year in 2012 Graft survival 85% Patient survival 75% Ceulemans LJ 2015 1 year Graft survival 62. 8% Patient survival 71. 1% 5 year: Graft survival 58. 7% Patient survival 53. 1% Grant 2015 Patient survival: 76%, 56% and 43% at 1, 5 and 10 years Rates of graft loss beyond 1 year have not improved

Transplantation • 5 hours cold ischaemic time • Higher level of immunosuppression • Higher risk of graft rejection • Higher risk of drug toxicity • Higher risk of lymphoproliferative disease