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Short Bowel Syndrome: Highlights of Patient Management, Quality of Life, and Survival Darlene G. Kelly, Kelly A. Tappenden and Marion F. Winkler JPEN J Parenter Enteral Nutr published online 18 November 2013 DOI: 10.1177/0148607113512678 The online version of this article can be found at: http://pen.sagepub.com/content/early/2013/11/15/0148607113512678 A more recent version of this article was published on - Apr 22, 2014
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PENXXX10.1177/0148607113512678Journal of Parenteral and Enteral NutritionKelly et al
Review
Short Bowel Syndrome: Highlights of Patient Management, Quality of Life, and Survival Darlene G. Kelly, MD, PhD, FACP, FACG1; Kelly A. Tappenden, PhD, RD2; and Marion F. Winkler, PhD, RD, LDN, CNSC3
Journal of Parenteral and Enteral Nutrition Volume XX Number X Month 2013 1–11 © 2013 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607113512678 jpen.sagepub.com hosted at online.sagepub.com
Abstract Short bowel syndrome (SBS) occurs as a result of intestinal resection, and in many patients is associated with complications, such as diarrhea, dehydration, weight loss, and nutrition deficiencies. Many individuals with SBS develop intestinal failure and require parenteral nutrition (PN) and/or intravenous (IV) fluids (PN/IV). Although PN is essential for survival, some patients with SBS who require longterm PN experience significant complications that contribute to morbidity and mortality. Consequently, therapies that decrease reliance on PN are of considerable importance. Intestinal adaptation, which results in morphologic and functional changes that increase performance of the remnant bowel, occurs spontaneously after intestinal resection. These effects can be enhanced with nutrition and pharmaceutical approaches. For example, oral or tube-fed nutrients stimulate growth and adaptation of intestinal tissues. In addition, prebiotics support growth of beneficial intestinal microbiota that produce short-chain fatty acids, which have been shown in preclinical studies to enhance intestinal structure and function. Finally, glucagon-like peptide 2 (GLP-2) is an endogenous peptide that promotes intestinal rehabilitation and improves intestinal absorption. Teduglutide, a recombinant human GLP-2 analog, has recently been approved in the United States for the treatment of adults with SBS who are dependent on PN. In pharmacodynamic and clinical studies, teduglutide has been shown to promote changes in intestinal structure, such as increases in villus height and crypt depth, and to improve intestinal absorption, as indicated by reduced PN/IV dependence. This article presents a brief overview of SBS, including effects on survival and quality of life and current treatment options. (JPEN J Parenter Enteral Nutr. XXXX;xx:xx-xx)
Keywords gastroenterology; parenteral nutrition; adults; home nutrition support; growth factors
Short Bowel Syndrome and Parenteral Nutrition: Background Short bowel syndrome (SBS) is a rare, complex clinical condition resulting from the loss of intestinal absorptive capacity due to surgical resection, congenital defect, or disease. Adult patients with SBS are highly heterogeneous, presenting with a wide range of underlying pathologic conditions, length and function of remaining bowel, and psychosocial characteristics. The symptom complex varies from patient to patient but is characterized by diarrhea, fatty stools, abdominal pain, malnutrition, and dehydration. Underlying conditions that may require intestinal resection include mesenteric ischemia, radiation enteritis, Crohn’s disease, trauma, and some congenital defects. Depending on the specific location of the resection, the anastomoses may be either ileocolonic or jejunocolonic, or there may be an endjejunostomy or ileostomy. Malnutrition associated with SBS progressively impairs the function of all body systems, leading to diminished overall health and quality of life. It increases susceptibility to disease, intensifies complications of illness and surgery, delays recovery, and increases mortality risk.1,2 Patients are at particular risk of hypotension and acute and chronic renal failure as a consequence of
dehydration and sodium deficiency.3 Another risk is gallstones resulting from gallbladder stasis. Hypomagnesemia, hypoalbuminemia, and hypocalcemia are common complications, with widespread clinical manifestations in multiple organ systems.3,4 From 1Emeritus Member, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota; 2Department of Food Science and Human Nutrition, University of Illinois at UrbanaChampaign, Urbana, Illinois; and 3Department of Surgery/Nutrition Support, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island. Financial disclosure: All authors had significant input to the content and revisions to the manuscript and received no compensation for their contributions. NPS Pharmaceuticals, Inc provided funding to Dr Heather Heerssen of Complete Healthcare Communications, Inc (CHC; Chadds Ford, PA) for writing assistance. Drs Kelly, Tappenden, and Winkler have served as paid consultants for NPS Pharmaceuticals, Inc. Received for publication July 17, 2013; accepted for publication October 21, 2013. Corresponding Author: Marion F. Winkler, PhD, RD, LDN, CNSC, Rhode Island Hospital, Warren Alpert Medical School of Brown University, 593 Eddy St, NAB 218, Providence, RI 02903, USA. Email: [email protected].
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Table 1. Prevalence Estimates of Home Parenteral Nutrition.13,14 Country Belgium Denmark France Netherlands Poland Spain United Kingdom
Prevalence Estimate per Million 3 12.7 3.6 3.7 1.1 5.1 3.7
In addition, most patients with SBS experience ongoing and lifestyle-altering diarrhea that is often unresponsive to dietary therapy and pharmacologic management. Patients who are unable to increase their oral intake sufficiently to meet their dietary needs or are unable to absorb sufficient nutrients despite a significant increase in oral intake require long-term parenteral nutrition (PN) and/or intravenous (IV) fluids (PN/IV) support. PN/IV, although life-saving, has limitations; severe complications that may occur either from the underlying SBS or its treatment, can be life-threatening.5 PN-associated complications include catheter-related blood stream infection, catheter obstruction, venous thrombosis, metabolic bone disease, liver dysfunction and failure, and impaired quality of life.6-11 Thus, there is a need for treatment approaches that enhance intestinal absorption of the remnant bowel and reduce the need for PN/IV support.
Epidemiology The incidence and prevalence of SBS are challenging to determine, in part because the condition is rare and there is a lack of consistently applied disease criteria. Therefore, the size of the SBS population has been approximated based on the prevalence of home PN (HPN) use. According to the most recent U.S. estimate, published in 1991, the HPN population in the United States included 20,000 patients; however, the relevance of this estimate to current numbers is unclear.12 European data indicate that HPN consumers vary by country, ranging from 1.1 to 12.7 per million adults (Table 1).13,14 Mughal and Irving estimated that in the United Kingdom, the incidence of patients requiring HPN was 2 patients per million.15 The most recent European data are from an HPN registry based in Spain, where the overall prevalence of HPN usage is 5 adults per million.13 However, HPN use varied widely by region, ranging from a prevalence of 1.4 per million in Canarias to 11.5 per million in Madrid.13 These large geographical differences likely reflect the greater availability of, and referral of patients to, intestinal rehabilitation programs that provide HPN in larger cities. Patients with SBS compose a sizeable proportion of the HPN population. Results of a 1997 survey of European HPN centers treating 756 patients revealed that 35% of HPN users were patients with SBS.14 A more recent study of the Spanish
HPN registry reported that patients with SBS made up 47% of the 148 patients (including 9 children) receiving HPN in Spain.16 Therefore, the prevalence of SBS can be broadly approximated from the number of HPN consumers.14 Based on the data in Table 1, the prevalence of SBS in Europe can be roughly estimated to be between 0.4 and 6.0 per million. However, this calculation does not include patients with SBS who die following resection or those who achieve independence from HPN. Thus, the size of the SBS population has yet to be accurately determined. In 2011, the American Society for Parenteral and Enteral Nutrition launched Sustain™, LLC, an online registry to collect information related to HPN cases in the United States.17 If participation of clinicians and infusion companies is comprehensive, this registry can be expected to establish accurate U.S. prevalence data for HPN and the relative number of people on HPN who have SBS. Not surprisingly, patients with SBS experience reduced long-term survival compared with the population as a whole. Overall, 2- and 5-year survival rates for patients with nonmalignant SBS have been reported as 86% and 75%, respectively.2 The 5-year survival probability in patients with nonmalignant SBS was negatively related to small bowel anatomy (end-jejunostomy), small bowel length (3 hours.118 Teduglutide is a targeted therapy that has been shown to increase villus height and crypt depth of the intestinal epithelium, resulting in enhanced absorptive capacity.117,119-121 The efficacy of teduglutide in the treatment of IF associated with SBS has been demonstrated in placebo-controlled as well as long-term phase III clinical studies.119,122,123 These studies have shown that teduglutide, administered as a daily subcutaneous injection at a dose of 0.05 mg/kg/day, significantly reduces PN/IV volume requirements and number of infusion days; in some cases, patients achieve independence from PN/IV.122,123 The most common adverse events to occur during teduglutide therapy in the phase III trials were gastrointestinal-related events, including abdominal pain, nausea, and vomiting.122,123 Three patients who received teduglutide as part of a 2-year extension study were diagnosed with malignancy; 1 patient with metastatic adenocarcinoma had prior Hodgkin’s disease and 2 patients with lung cancer had extensive smoking histories.124 In 2012, teduglutide was approved by the FDA for the treatment of adult patients with SBS who are dependent on PN support. Teduglutide is recommended for clinically stable patients with nonobstructive, nonmalignant disease who require PN even following optimization of diet, hydration, and adjunctive medications.125 Because of the potential for the acceleration of hyperplasia with teduglutide, a colonoscopy to evaluate the occurrence of polyps is recommended before treatment initiation, along with periodic follow-up colonoscopies.37,126 In addition, teduglutide is contraindicated in patients with current or a past malignancy, except for basal cell carcinoma. In the event of intestinal malignancy, teduglutide should be discontinued.125
Conclusions The overall health and quality of life of patients with SBS is negatively affected by the symptoms of the condition. In
addition, PN, the primary treatment for IF associated with SBS, can have a high rate of complications. Patients with endorgan disease, multiple severe adverse events related to PN, or IF may be suitable for intestinal transplantation. However, for many patients with SBS, enhancing intestinal adaptation can both mitigate the symptoms of SBS and reduce dependence on PN and may be a preferable alternative to additional intestinal surgery. A primary means of encouraging intestinal adaptation is through oral nutrition, which should be strongly encouraged. Emerging data indicate that newer therapeutic options, such as GLP-2/teduglutide, may also promote intestinal rehabilitation. In addition, clinicians can promote enhanced quality of life through comprehensive patient education and management of patient expectations regarding the PN experience.
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84. Persoon A, Huisman-de Waal G, Naber TA, et al. Impact of long-term HPN on daily life in adults. Clin Nutr. 2005;24:304-313. 85. Lehoux P, Saint-Arnaud J, Richard L. The use of technology at home: what patient manuals say and sell vs. what patients face and fear. Sociol Health Illn. 2004;26:617-644. 86. Hall RC, Stickney SK, Gardner ER, Popkin MK. Psychiatric reactions to long-term intravenous hyperalimentation. Psychosomatics. 1981;22: 428-443. 87. Stern J. Home parenteral nutrition and the psyche: psychological challenges for patient and family. Proc Nutr Soc. 2006;65:222-226. 88. MacRitchie KJ. Parenteral nutrition outside hospital: psychosocial styles of adaptation. Can J Psychiatry. 1980;25:308-313. 89. Silver HJ. The lived experience of home total parenteral nutrition: an online qualitative inquiry with adults, children, and mothers. Nutr Clin Pract. 2004;19:297-304. 90. Huisman-de Waal G, Schoonhoven L, Jansen J, Wanten G, van Achterberg T. The impact of home parenteral nutrition on daily life-a review. Clin Nutr. 2007;26:275-288. 91. Malone M. Longitudinal assessment of outcome, health status, and changes in lifestyle associated with long-term home parenteral and enteral nutrition. JPEN J Parenter Enteral Nutr. 2002;26:164-168. 92. Fortune DG, Varden J, Parker S, Harper L, Richards HL, Shaffer JL. Illness beliefs of patients on home parenteral nutrition (HPN) and their relation to emotional distress. Clin Nutr. 2005;24:896-903. 93. Robb RA, Brakebill JI, Ivey MF, Christensen DB, Young JH, Scribner BH. Subjective assessment of patient outcomes of home parenteral nutrition. Am J Hosp Pharm. 1983;40:1646-1650. 94. Herfindal ET, Bernstein LR, Kudzia K, Wong A. Survey of home nutritional support patients. JPEN J Parenter Enteral Nutr. 1989;13: 255-261. 95. Huisman-de Waal G, Naber T, Schoonhoven L, Persoon A, Sauerwein H, van Achterberg T. Problems experienced by patients receiving parenteral nutrition at home: results of an open interview study. JPEN J Parenter Enteral Nutr. 2006;30:215-221. 96. Lehoux P. Patients’ perspectives on high-tech home care: a qualitative inquiry into the user-friendliness of four technologies. BMC Health Serv Res. 2004;4:28. 97. Scolapio JS, Savoy AD, Kaplan J, Burger CD, Lin SC. Sleep patterns of cyclic parenteral nutrition, a pilot study: are there sleepless nights? JPEN J Parenter Enteral Nutr. 2002;26:214-217. 98. Winkler MF, Wetle T, Smith C, Hagan E, O’Sullivan Maillet J, TougerDecker R. The meaning of food and eating among home parenteral nutrition-dependent adults with intestinal failure: a qualitative inquiry. J Am Diet Assoc. 2010;110:1676-1683. 99. Robinson CA. Managing life with a chronic condition: the story of normalization. Qual Health Res. 1993;3:6-28. 100. Smith CE, Curtas S, Werkowitch M, Kleinbeck SV, Howard L. Home parenteral nutrition: does affiliation with a national support and educational organization improve patient outcomes? JPEN J Parenter Enteral Nutr. 2002;26:159-163. 101. Buchman AL. Short-bowel syndrome. Clin Gastroenterol Hepatol. 2005;3:1066-1070. 102. Matarese LE. Nutrition and fluid optimization for patients with short bowel syndrome. JPEN J Parenter Enteral Nutr. 2013;37:161-170. 103. Goulet O, Ruemmele F. Causes and management of intestinal failure in children. Gastroenterology. 2006;130:S16-S28. 104. Placidi E, Marciani L, Hoad CL, et al. The effects of loperamide, or loperamide plus simethicone, on the distribution of gut water as assessed by MRI in a mannitol model of secretory diarrhoea. Aliment Pharmacol Ther. 2012;36:64-73. 105. Van Wyk M, Sommers DK, Steyn AG. Evaluation of gastrointestinal motility using the hydrogen breath test. Br J Clin Pharmacol. 1985;20: 479-481. 106. Nguyen BT, Blatchford GJ, Thompson JS, Bragg LE. Should intestinal continuity be restored after massive intestinal resection? Am J Surg. 1989;158:577-579; discussion 579-580.
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107. Thompson JS, Langnas AN. Surgical approaches to improving intestinal function in the short-bowel syndrome. Arch Surg. 1999;134:706-709; discussion 709-711. 108. Bianchi A. Intestinal loop lengthening—a technique for increasing small intestinal length. J Pediatr Surg. 1980;15:145-151. 109. Thompson JS, Rochling FA, Weseman RA, Mercer DF. Current management of short bowel syndrome. Curr Probl Surg. 2012;49:52-115. 110. Gibson LD, Carter R, Hinshaw DB. Segmental reversal of small intestine after massive bowel resection. Successful case with follow-up examination. JAMA. 1962;182:952-954. 111. Abu-Elmagd KM, Costa G, Bond GJ, et al. Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg. 2009;250:567-581. 112. Salvino R, Ghanta R, Seidner DL, Mascha E, Xu Y, Steiger E. Liver failure is uncommon in adults receiving long-term parenteral nutrition. JPEN J Parenter Enteral Nutr. 2006;30:202-208. 113. Byrne TA, Morrissey TB, Nattakom TV, Ziegler TR, Wilmore DW. Growth hormone, glutamine, and a modified diet enhance nutrient absorption in patients with severe short bowel syndrome. JPEN J Parenter Enteral Nutr. 1995;19:296-302. 114. Wales PW, Nasr A, de Silva N, Yamada J. Human growth hormone and glutamine for patients with short bowel syndrome. Cochrane Database Syst Rev. 2010CD006321. 115. Drucker DJ. Gut adaptation and the glucagon-like peptides. Gut. 2002;50:428-435. 116. Dahly EM, Gillingham MB, Guo Z, et al. Role of luminal nutrients and endogenous GLP-2 in intestinal adaptation to mid-small bowel resection. Am J Physiol Gastrointest Liver Physiol. 2003;284:G670-G682. 117. Jeppesen PB, Sanguinetti EL, Buchman A, 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;54:1224-1231. 118. Marier JF, Beliveau M, Mouksassi MS, et al. Pharmacokinetics, safety, and tolerability of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, following multiple ascending subcutaneous administrations in healthy subjects. J Clin Pharmacol. 2008;48:1289-1299.
119. Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O’Keefe SJ. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut. 2011;60:902-914. 120. Winker MF, Fujioka K, Youssef N, et al. Teduglutide enhances nutrient absorption in adult subjects with short bowel syndrome and maintains nutritional balance despite significant reductions in parenteral support. JPEN J Parenter Enteral Nutr. 2012;36:127-128. 121. Tappenden KA, Edelman J, Joelsson B. Teduglutide enhances structural adaptation of the small intestinal mucosa in patients with short bowel syndrome. J Clin Gastroenterol. 2013;47:602-607. 122. Jeppesen PB, Pertkiewicz M, Messing B, et al. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology. 2012;143:1473-1481, e1473. 123. O’Keefe SJ, Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B. Safety and efficacy of teduglutide after 52 weeks of treatment in patients with short bowel syndrome-intestinal failure. Clin Gastroenterol Hepatol. 2013;11:815-823. 124. Schwartz LK, Seidner DL, Jeppesen PB, Pertkiewicz M, Youssef N, Heinze H. Teduglutide (TED) for the treatment of short bowel syndromeintestinal failure (SBS-IF) subjects yields further reductions in parenteral support (PS): an interim assessment of a 2-year, open-label, phase 3 trial (STEPS2). Am J Gastroenterol. 2011;106:S99. 125. Seidner DL, Schwartz LK, Winkler MF, Jeejeebhoy K, Boullata JI, Tappenden KA. Increased intestinal absorption in the era of teduglutide and its impact on management strategies in patients with short bowel syndrome-associated intestinal failure. JPEN J Parenter Enteral Nutr. 2013;37:201-211. 126. Jeppesen PB. The non-surgical treatment of adult patients with short bowel syndrome. Expert Opin Orphan Drugs. 2013;1:527-538. 127. Gennari FJ, Weise WJ. Acid-base disturbances in gastrointestinal disease. Clin J Am Soc Nephrol. 2008;3:1861-1868. 128. Richards DM, Scott NA, Shaffer JL, Irving M. Opiate and sedative dependence predicts a poor outcome for patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr. 1997;21:336-338.
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Short Bowel Syndrome: Highlights of Patient Management, Quality of Life, and Survival Darlene G. Kelly, Kelly A. Tappenden and Marion F. Winkler JPEN J Parenter Enteral Nutr published online 18 November 2013 DOI: 10.1177/0148607113512678 The online version of this article can be found at: http://pen.sagepub.com/content/early/2013/11/15/0148607113512678 A more recent version of this article was published on - Apr 22, 2014
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512678
research-article2013
PENXXX10.1177/0148607113512678Journal of Parenteral and Enteral NutritionKelly et al
Review
Short Bowel Syndrome: Highlights of Patient Management, Quality of Life, and Survival Darlene G. Kelly, MD, PhD, FACP, FACG1; Kelly A. Tappenden, PhD, RD2; and Marion F. Winkler, PhD, RD, LDN, CNSC3
Journal of Parenteral and Enteral Nutrition Volume XX Number X Month 2013 1–11 © 2013 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607113512678 jpen.sagepub.com hosted at online.sagepub.com
Abstract Short bowel syndrome (SBS) occurs as a result of intestinal resection, and in many patients is associated with complications, such as diarrhea, dehydration, weight loss, and nutrition deficiencies. Many individuals with SBS develop intestinal failure and require parenteral nutrition (PN) and/or intravenous (IV) fluids (PN/IV). Although PN is essential for survival, some patients with SBS who require longterm PN experience significant complications that contribute to morbidity and mortality. Consequently, therapies that decrease reliance on PN are of considerable importance. Intestinal adaptation, which results in morphologic and functional changes that increase performance of the remnant bowel, occurs spontaneously after intestinal resection. These effects can be enhanced with nutrition and pharmaceutical approaches. For example, oral or tube-fed nutrients stimulate growth and adaptation of intestinal tissues. In addition, prebiotics support growth of beneficial intestinal microbiota that produce short-chain fatty acids, which have been shown in preclinical studies to enhance intestinal structure and function. Finally, glucagon-like peptide 2 (GLP-2) is an endogenous peptide that promotes intestinal rehabilitation and improves intestinal absorption. Teduglutide, a recombinant human GLP-2 analog, has recently been approved in the United States for the treatment of adults with SBS who are dependent on PN. In pharmacodynamic and clinical studies, teduglutide has been shown to promote changes in intestinal structure, such as increases in villus height and crypt depth, and to improve intestinal absorption, as indicated by reduced PN/IV dependence. This article presents a brief overview of SBS, including effects on survival and quality of life and current treatment options. (JPEN J Parenter Enteral Nutr. XXXX;xx:xx-xx)
Keywords gastroenterology; parenteral nutrition; adults; home nutrition support; growth factors
Short Bowel Syndrome and Parenteral Nutrition: Background Short bowel syndrome (SBS) is a rare, complex clinical condition resulting from the loss of intestinal absorptive capacity due to surgical resection, congenital defect, or disease. Adult patients with SBS are highly heterogeneous, presenting with a wide range of underlying pathologic conditions, length and function of remaining bowel, and psychosocial characteristics. The symptom complex varies from patient to patient but is characterized by diarrhea, fatty stools, abdominal pain, malnutrition, and dehydration. Underlying conditions that may require intestinal resection include mesenteric ischemia, radiation enteritis, Crohn’s disease, trauma, and some congenital defects. Depending on the specific location of the resection, the anastomoses may be either ileocolonic or jejunocolonic, or there may be an endjejunostomy or ileostomy. Malnutrition associated with SBS progressively impairs the function of all body systems, leading to diminished overall health and quality of life. It increases susceptibility to disease, intensifies complications of illness and surgery, delays recovery, and increases mortality risk.1,2 Patients are at particular risk of hypotension and acute and chronic renal failure as a consequence of
dehydration and sodium deficiency.3 Another risk is gallstones resulting from gallbladder stasis. Hypomagnesemia, hypoalbuminemia, and hypocalcemia are common complications, with widespread clinical manifestations in multiple organ systems.3,4 From 1Emeritus Member, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota; 2Department of Food Science and Human Nutrition, University of Illinois at UrbanaChampaign, Urbana, Illinois; and 3Department of Surgery/Nutrition Support, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island. Financial disclosure: All authors had significant input to the content and revisions to the manuscript and received no compensation for their contributions. NPS Pharmaceuticals, Inc provided funding to Dr Heather Heerssen of Complete Healthcare Communications, Inc (CHC; Chadds Ford, PA) for writing assistance. Drs Kelly, Tappenden, and Winkler have served as paid consultants for NPS Pharmaceuticals, Inc. Received for publication July 17, 2013; accepted for publication October 21, 2013. Corresponding Author: Marion F. Winkler, PhD, RD, LDN, CNSC, Rhode Island Hospital, Warren Alpert Medical School of Brown University, 593 Eddy St, NAB 218, Providence, RI 02903, USA. Email: [email protected].
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Table 1. Prevalence Estimates of Home Parenteral Nutrition.13,14 Country Belgium Denmark France Netherlands Poland Spain United Kingdom
Prevalence Estimate per Million 3 12.7 3.6 3.7 1.1 5.1 3.7
In addition, most patients with SBS experience ongoing and lifestyle-altering diarrhea that is often unresponsive to dietary therapy and pharmacologic management. Patients who are unable to increase their oral intake sufficiently to meet their dietary needs or are unable to absorb sufficient nutrients despite a significant increase in oral intake require long-term parenteral nutrition (PN) and/or intravenous (IV) fluids (PN/IV) support. PN/IV, although life-saving, has limitations; severe complications that may occur either from the underlying SBS or its treatment, can be life-threatening.5 PN-associated complications include catheter-related blood stream infection, catheter obstruction, venous thrombosis, metabolic bone disease, liver dysfunction and failure, and impaired quality of life.6-11 Thus, there is a need for treatment approaches that enhance intestinal absorption of the remnant bowel and reduce the need for PN/IV support.
Epidemiology The incidence and prevalence of SBS are challenging to determine, in part because the condition is rare and there is a lack of consistently applied disease criteria. Therefore, the size of the SBS population has been approximated based on the prevalence of home PN (HPN) use. According to the most recent U.S. estimate, published in 1991, the HPN population in the United States included 20,000 patients; however, the relevance of this estimate to current numbers is unclear.12 European data indicate that HPN consumers vary by country, ranging from 1.1 to 12.7 per million adults (Table 1).13,14 Mughal and Irving estimated that in the United Kingdom, the incidence of patients requiring HPN was 2 patients per million.15 The most recent European data are from an HPN registry based in Spain, where the overall prevalence of HPN usage is 5 adults per million.13 However, HPN use varied widely by region, ranging from a prevalence of 1.4 per million in Canarias to 11.5 per million in Madrid.13 These large geographical differences likely reflect the greater availability of, and referral of patients to, intestinal rehabilitation programs that provide HPN in larger cities. Patients with SBS compose a sizeable proportion of the HPN population. Results of a 1997 survey of European HPN centers treating 756 patients revealed that 35% of HPN users were patients with SBS.14 A more recent study of the Spanish
HPN registry reported that patients with SBS made up 47% of the 148 patients (including 9 children) receiving HPN in Spain.16 Therefore, the prevalence of SBS can be broadly approximated from the number of HPN consumers.14 Based on the data in Table 1, the prevalence of SBS in Europe can be roughly estimated to be between 0.4 and 6.0 per million. However, this calculation does not include patients with SBS who die following resection or those who achieve independence from HPN. Thus, the size of the SBS population has yet to be accurately determined. In 2011, the American Society for Parenteral and Enteral Nutrition launched Sustain™, LLC, an online registry to collect information related to HPN cases in the United States.17 If participation of clinicians and infusion companies is comprehensive, this registry can be expected to establish accurate U.S. prevalence data for HPN and the relative number of people on HPN who have SBS. Not surprisingly, patients with SBS experience reduced long-term survival compared with the population as a whole. Overall, 2- and 5-year survival rates for patients with nonmalignant SBS have been reported as 86% and 75%, respectively.2 The 5-year survival probability in patients with nonmalignant SBS was negatively related to small bowel anatomy (end-jejunostomy), small bowel length (3 hours.118 Teduglutide is a targeted therapy that has been shown to increase villus height and crypt depth of the intestinal epithelium, resulting in enhanced absorptive capacity.117,119-121 The efficacy of teduglutide in the treatment of IF associated with SBS has been demonstrated in placebo-controlled as well as long-term phase III clinical studies.119,122,123 These studies have shown that teduglutide, administered as a daily subcutaneous injection at a dose of 0.05 mg/kg/day, significantly reduces PN/IV volume requirements and number of infusion days; in some cases, patients achieve independence from PN/IV.122,123 The most common adverse events to occur during teduglutide therapy in the phase III trials were gastrointestinal-related events, including abdominal pain, nausea, and vomiting.122,123 Three patients who received teduglutide as part of a 2-year extension study were diagnosed with malignancy; 1 patient with metastatic adenocarcinoma had prior Hodgkin’s disease and 2 patients with lung cancer had extensive smoking histories.124 In 2012, teduglutide was approved by the FDA for the treatment of adult patients with SBS who are dependent on PN support. Teduglutide is recommended for clinically stable patients with nonobstructive, nonmalignant disease who require PN even following optimization of diet, hydration, and adjunctive medications.125 Because of the potential for the acceleration of hyperplasia with teduglutide, a colonoscopy to evaluate the occurrence of polyps is recommended before treatment initiation, along with periodic follow-up colonoscopies.37,126 In addition, teduglutide is contraindicated in patients with current or a past malignancy, except for basal cell carcinoma. In the event of intestinal malignancy, teduglutide should be discontinued.125
Conclusions The overall health and quality of life of patients with SBS is negatively affected by the symptoms of the condition. In
addition, PN, the primary treatment for IF associated with SBS, can have a high rate of complications. Patients with endorgan disease, multiple severe adverse events related to PN, or IF may be suitable for intestinal transplantation. However, for many patients with SBS, enhancing intestinal adaptation can both mitigate the symptoms of SBS and reduce dependence on PN and may be a preferable alternative to additional intestinal surgery. A primary means of encouraging intestinal adaptation is through oral nutrition, which should be strongly encouraged. Emerging data indicate that newer therapeutic options, such as GLP-2/teduglutide, may also promote intestinal rehabilitation. In addition, clinicians can promote enhanced quality of life through comprehensive patient education and management of patient expectations regarding the PN experience.
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