Parenteral Nutrition: Transient or Permanent Therapy in Intestinal Failure?

GASTROENTEROLOGY 2006;130:S37–S42

EDITORIAL Parenteral Nutrition: Transient or Permanent Therapy in Intestinal Failure? ntestinal failure has been defined as the reduction of functional gut mass below the minimal amount necessary for adequate digestion and absorption to meet nutrient and fluid requirements in adults and growth in children.1 Intestinal failure can be due to actual or effective loss of gut mucosal absorptive surface area, as in short bowel syndrome (SBS) following massive small bowel resection (SBR), the most common cause, and various congenital anomalies (eg, intestinal atresia, microvillus inclusion disease, intestinal epithelial dysplasia). Intestinal failure can also be due to mucosal diseases (eg, inflammatory bowel disease, severe villous atrophy), dysmotility disorders (eg, pseudo-obstruction), severe maldigestive disorders, and other conditions.1– 8 Individuals with intestinal failure exhibit chronic diarrhea and malabsorption and experience varying degrees of dehydration, weight loss, micronutrient and protein-energy depletion, weakness, and increased mortality rates.1– 8 Thus, a mainstay of treatment in intestinal failure involves specialized enteral and/or parenteral nutrition support to treat malnutrition and prevent malnutritionassociated morbidity. Although oral nutrient intake is possible in most individuals with SBS, in light of the underlying bowel disorder most such patients require intermittent or chronic home parenteral nutrition (PN) and/or intravenous hydration/electrolyte therapy as a critical component of care, particularly in the early months to years after SBR. The lifesaving effect of PN in children and adults with intestinal failure was dramatically illustrated in the late 1960s and early 1970s, during which time standardized modalities for delivery of complete intravenous solutions containing essential micronutrients, energy, fat, and amino acids were first developed.2–5 In patients with SBS, several reports describe specific bowel anatomic criteria that typically enable eventual independence from PN (eg, length and location of residual small bowel, presence or absence of the ileal-cecal valve and/or residual colon).6 – 8 In recent years, the concept of intestinal rehabilitation using enteral nutrition and gut-trophic growth factors to facilitate weaning from PN in SBS has been developed.9 –13 This approach utilizes individualized oral diets, specific nutrient substrates (eg, glutamine, vitamin A, short-chain fatty acids [SCFA]), and/or peptide

I

growth factors (eg, growth hormone [GH], glucagonlike peptide-2 ([GLP-2]) as methods to improve gut absorptive function.9 –13 However, the important role of PN to ensure adequate macro- and micronutrient delivery to tissues and thus enable optimal adaptation of residual small bowel in SBS has long been recognized.14 In this section of GASTROENTEROLOGY, Drs Jeejeebhoy, Messing, and Howard review relevant data on use of PN and modalities of intestinal rehabilitation in patients with SBS and other forms of chronic intestinal failure.15–17

Guidelines for Management of Short Bowel Syndrome: Strategies to Reduce Parenteral Nutrition Dependence As outlined by Jeejeebhoy in this volume, the specialized physiologic functions of jejunum, ileum, and colon, coupled with the residual length of these gut segments, dictate the net degree of malabsorption and tolerance of specific luminal nutrients in patients with SBS.15 During the first few years after SBR, patients with SBS typically experience a gradual decrease in diarrheal volume and improved tolerance to oral diet, suggesting that improved endogenous absorptive function occurs. In animal models, this process involves dynamic hypertrophy and hyperplasia of small bowel and, to a lesser extent, colonic mucosa and submucosa after massive bowel resection, a process termed intestinal adaptation.11 Unfortunately, surprisingly little data in human SBS have been published on the time course, magnitude, and regulation of endogenous or diet/growth-factor stimulated gut mucosal adaptation.18 –20 The few available studies do not demonstrate the dynamic gut mucosal growth response after SBR as observed in animal models of SBS.18 –20 However, these are limited by subject heterogeneity, small sample sizes, lack of serial samples, and few observations within the initial few years after SBR, when gut adaptation is most apparent clinically. Also, only a few case reports have examined bowel microvillus changes in human SBS.18 Serial ultrastructural studies of gut mucosal cells after SBR would be useful because small bowel and colonic microvilli comprise the major portion of absorptive surface area.

S38

EDITORIAL

As outlined by Jeejeebhoy, the presence of food in the intestinal lumen via enteral feeding is a clear stimulus for small bowel mucosal growth in animal models.15 Mechanisms for this effect are incompletely understood, but likely involve endogenous mucosal growth factor expression, increased splanchnic blood flow, and several other factors.11,21 In animal models, administration of PN maintains somatic growth, but is associated with small bowel mucosal atrophy/hypoplasia, variably decreased expression/function of gut digestive/transport molecules, and abnormal gut barrier function; these abnormalities are prevented or reversed with a relatively modest amount of enteral feeding.11,15 Unfortunately, only limited information on gut mucosal effects of bowel rest during total PN are available in humans and these data are conflicting with regard to mucosal growth and digestive enzyme activity.15 However, several studies, including those described by Messing et al in this volume of GASTROENTEROLOGY, suggest that SBS patients exhibit adaptive hyperphagia after massive SBR and aggressive use of enteral feeding enhances absorptive function over time.16,22–24 This modality (usually via nocturnal tube feeding) is routinely used in pediatric SBS patients and appears to enhance gut function.24 Serial data on gut mucosal histology, absorptive/barrier functions, and underlying mucosal mechanisms with enteral feeding modalities in human SBS are sorely needed. With regard to use of specific dietary nutrients, colonic conservation of malabsorbed carbohydrate and soluble fiber via bacterial fermentation of these substrates to SCFA is well described in humans.25 The ability of SCFA to stimulate water and sodium absorption and mucosal growth and their use as energy substrates has led to emphasis on complex carbohydrates as a component of individualized dietary recommendations for SBS patients with residual colon.15,24,25 Studies by Jeejeebhoy and other studies showed that the level of dietary fat intake in SBS patients without residual colon does not alter stool output.15,25–26 Thus, fat, as an important source of energy, need not be limited in most such SBS patients, although higher intakes may worsen calcium, magnesium, zinc, and copper losses.27 It is also easier to meet needs for energy and protein/amino acid nitrogen than for electrolytes and divalent ions (eg, calcium, magnesium) in SBS.15 Unfortunately, serial expression and function of specific digestive enzymes and nutrient and electrolyte transporters along human gut mucosa has been very little studied in SBS. In a recent study, adults with chronic SBS exhibited a marked up-regulation of the di/tripeptide transporter PepT1 in colonic mucosa compared with a low level of expression in the colon of control subjects.20 This potential adaptive mechanism in

GASTROENTEROLOGY Vol. 130, No. 2

SBS suggests the potential utility of supplementation of oral diets or rehydration solutions with di- or tripeptides as a strategy to improve amino acid nitrogen accrual in SBS patients with residual colon.20 Additional data on changes in small bowel and colonic nutrient transporter expression and function are needed to advance understanding of human gut adaptation and would guide dietary recommendations for gut rehabilitation in SBS patients. In addition to the concepts outlined previously, use of small frequent feedings, oral rehydration solutions (containing adequate sodium which stimulates amino acid and glucose absorption), provision of adequate protein, and avoidance of simple sugars and lactose are major principles that may enhance gut nutrient absorption in individual patients with SBS.15–16,26 Unfortunately, SBS patients not followed in a bowel rehabilitation center often consume habitual diets likely to worsen diarrhea and thus increase PN dependence.28 As outlined by Jeejeebhoy, maintenance of normal serum levels of essential micronutrients and electrolytes often requires parenteral administration, even in SBS subjects otherwise weaned from PN.15 Although use of specific nutrients (eg, glutamine, zinc, vitamin A) to enhance gut mucosal growth and function show some promise in animal models of SBS,11,15 data in human SBS are absent, or in the case of glutamine, conflicting. New data on the potential efficacy of supplementation of these nutrients after correction of specific deficiencies are needed. As outlined by Jeejeebhoy, Messing, and other authors in this supplement, successful use of enteral nutrition for patients with SBS depends on length and function of residual small bowel and colon and several practical considerations, including subject compliance with dietary changes and ability to prepare smaller, more frequent meals, and appropriate control of diarrheal volume with medications, including proton pump inhibitors and agents such as loperamide, phenoxylate, codeine, and tincture of opium.15–16,26 In addition, water-solubilized preparations of vitamins A, D, E, and K are now commercially available. In our experience, SBS patients not followed in a bowel rehabilitation center are often prescribed inadequate amounts of anti-diarrheal medications by physicians. Of interest, a recent study suggests that the antihypertensive agent clonidine may be an effective oral agent to decrease intestinal fluid losses in SBS patients with high-volume diarrhea.29 Patients with SBS often develop catheter and other infections due to gram-negative enteric bacilli.30 –32 Also PN-dependent adults with SBS were shown to have a high incidence of detectable flagellin and lipopolysaccharide (LPS) present intermittently in serum, together with

February Supplement 2006

markedly elevated flagellin-specific immunoglobulins.33 Together the studies suggest that a decrease in gut barrier function leading to translocation of luminal bacteria occurred in these individuals. Another understudied, but important clinical problem is small bowel bacterial overgrowth (SBBO), which is apparently common in SBS.34 –36 Patients with SBS have numerous risk factors for SBBO including: surgical blind loops (eg, endto-side anastomosis), anatomic disruptions leading to intestinal dysmotility and stasis (strictures, adhesions, mucosal inflammation), underlying Crohn’s disease, resection of the ileal-cecal valve, hypochlorhydria (induced by use of proton-pump inhibitors or H2 blockers) and malnutrition- or illness-associated immunodeficiency.35–36 Also, many of the signs and symptoms experienced chronically or intermittently by SBS patients are indistinguishable from classic symptoms of SBBO— diarrhea, steatorrhea, abdominal pain, bloating, cramping, and weight loss. SBBO causes malabsorption of protein, fat (and fat-soluble vitamins), and carbohydrate by direct and indirect effects of the overgrown bacteria, including deconjugation of bile salts with resultant steatorrhea and bile salt injury to colon, depletion or interference with disaccharidases, trypsin, and other digestive enzymes and nutrient transporters, and direct bacterial/toxin injury to absorptive cells, with associated local inflammation, villus blunting, protein-losing enteropathy, and abnormal permeability.35–36 Use of probiotics to treat a variety of intestinal disorders including SBBO has been increasingly studied.37 A few case reports describe efficacy of probiotics in SBS.13,38 However, at least three cases of bacteremia caused by the ingested probiotic bacteria in infants with PN-dependent SBS have been reported.39 – 40 The role of subject age and gut barrier dysfunction in these examples of bacterial translocation is unknown. To our knowledge, there are no published randomized controlled trials in SBS on the safety or efficacy of different antibiotics or probiotics as methods to treat SBBO (and thus potentially decrease malabsorption), although these agents are commonly prescribed empirically. Also unknown is whether different dietary constituents alter endogenous luminal flora in SBS. As outlined in detail elsewhere in this volume, several pharmacologic agents are being investigated as methods to promote absorption in SBS, with or without concomitant dietary manipulations, including octreotide,15 recombinant GH,41– 44 and forms of GLP2.45– 46 Octreotide appears to be particularly useful in the early phase after massive SBR as a method to decrease massive fluid and electrolyte losses,19 although its long-term use remains controversial. Both GH and GLP-2 have shown promise in small random-

EDITORIAL

S39

ized clinical trials in SBS.41– 43,45– 46 Of note, the US Food and Drug Administration recently approved recombinant human growth hormone for SBS, with or without supplemental glutamine, based on a doubleblind, randomized registration trial in 41 PN-dependent adults.42 Further studies are needed on the potential utility of gut-trophic and cytoprotective growth factor combinations and combinations of growth factors with specific nutrients in SBS.11,47 Information is also needed to help predict beneficial responses to these agents among individuals, given the heterogeneity of bowel function in SBS and the evident variations in metabolic/clinical responses in the patients studied to date in investigations of growth factor therapy.9 –12,46

Impact and Management of Home Parenteral Nutrition in Intestinal Failure Well-referenced papers by Messing et al16 and Howard17 in this volume outline the significant metabolic, infectious, mechanical, and psychological complications, and huge financial cost of home PN in subjects with intestinal failure.48 –55 Clearly more information is needed on novel therapies or new approaches to prevent and treat the devastating complications of liver failure and recurrent catheter infection that occur in many patients receiving chronic PN.48 –50 In addition, the potential biomarker role of plasma levels of citrulline in adults and children16,51–52 and GLP-2 in children,53 have been proposed. Additional studies to define and optimize appropriate biomarkers of intestinal growth and absorptive and barrier functions would help to refine clinical care for patients with SBS. As noted by Messing et al, care of individuals with intestinal failure is clearly best accomplished by a multidisciplinary nutrition support team and should include a detailed educational program that covers PN line care and dietary and other treatment issues.16 Data presented by Howard demonstrates that in addition to the primary diagnosis, age, and length and type of residual bowel, the experience of the supervising clinician is significantly related to overall survival in home PN patients.17 In the United States, there is clearly a wide difference in experience among physicians with regard to use of PN in general and care of gut failure patients in particular. As noted previously, SBS patients receiving PN not followed in a bowel rehabilitation center appear to habitually consume oral diets that would be expected to worsen diarrhea; these individuals were infrequently given any appropriate diet instruction (eg, use of oral rehydration

S40

EDITORIAL

fluids, avoidance of simple sugars) or oral nutrient supplements.28 In addition, various agents are readily available to gut failure patients without a prescription (eg, probiotics and nutrient supplements) and are indiscriminately used. Human GH was recently approved by the FDA for SBS based on a recently published randomized controlled trial,42 but very few clinicians have experience with this agent. Also, optimal efficacy of any bowel rehabilitation strategy likely depends on an appropriate dietary prescription individualized for each patient. The dietary regimen becomes even more important as patients are weaned from their PN “lifeline.” Thus, as pointed out by Messing and Howard, a strong argument can be made that intestinal failure patients requiring home PN should be followed primarily in specialized centers of excellence, as is routine in Europe.16 –17 Such clinical care centers for these complex patients need to be increasingly developed within academic medical centers in the United States. As outlined by Howard,17 affiliation with a peer support and educational organization56 (Oley Foundation for Home Parenteral and Enteral Nutrition) greatly reduced the incidence of sepsis in PNrequiring intestinal failure patients.17 Physicians can thus refer patients and their families to this resource, experienced bowel rehabilitation centers, and appropriate educational websites as a routine component of clinical care.17 Finally, given the critical impact that even a few feet of additional in-continuity bowel has on the ability of gut failure subjects to be weaned from PN, such restorative operations, particularly to establish colonic continuity, should be carefully considered in all PNdependent SBS patients in whom such operations are possible.16 –17 The extremely high financial cost of life-saving PN is frequently devastating to patients and/or their families. In light of the orphan nature of PN-dependent intestinal failure, a strong case can be made to help ease this financial burden at the federal level, as is the case in patients requiring equally life-saving chronic dialysis therapy. Federal payers should ideally allow physicians more flexibility in terms of the number of PN days deemed mandatory for individual patients in order for this expensive therapy to be covered by federal programs. This is important because it is common during intestinal rehabilitation and PN weaning for individual PN needs (days of therapy required per week) to fluctuate as a function of illness or dietary indiscretion.

Future Research Directions Significant questions remain with regard to both optimal delivery of PN and optimal methods to facilitate

GASTROENTEROLOGY Vol. 130, No. 2

Table 1. Unmet Research Needs Relevant to PN Use in Patients With Intestinal Failure Natural history of endogenous gut mucosal adaptive growth and absorptive/barrier functions in adult and pediatric SBS Appropriate biomarkers of intestinal growth and function Metabolic, mucosal, and clinical effects and long-term safety of nutrient/growth factor combinations (eg, glutamine ⫹ GLP-2) and growth factor combinations (eg, KGF and GH) Optimization of individualized oral diet/enteral tube feeds, oral rehydration solutions, and anti-diarrheal medications Regulation of endogenous gut flora by diet and probiotics; incidence of SBBO and efficacy of SBBO treatment to improve nutrient absorption Metabolic and clinical efficacy of newer PN lipid emulsions (eg, fish oil) and altered amino acid and micronutrient composition in patients requiring chronic PN Predictive factors for individual responses to new therapeutic approaches in intestinal rehabilitation Underlying gut mucosal mechanisms of endogenous and stimulated intestinal adaptation (eg, cell proliferation, apoptosis, changes in microvillus mass and nutrient transporter expression/function) Optimal methods to prevent and treat PN-associated cholestatis, liver dysfunction, and catheter-related infections and venous thrombosis Impact of tertiary rehabilitation centers of excellence, focused support groups, and non-hospital care facilities on quality of life and clinical/financial outcomes in SBS and other forms of intestinal failure NOTE. PN, parenteral nutrition; SBBO, small bowel bacterial overgrowth; SBS, short bowel syndrome.

PN weaning in patients with intestinal failure (Table 1). Answers to these questions will require considerable research investment. However, such studies should be relevant to other groups of patients requiring PN and translate to improved clinical care and decreased human and financial costs for subjects with the devastating orphan diseases that comprise intestinal failure. THOMAS R. ZIEGLER*,‡,§ LORRAINE M. LEADER‡ *Divisions of Endocrinology, Metabolism and Lipids and ‡Digestive Diseases and the § Center for Clinical and Molecular Nutrition Department of Medicine Emory University School of Medicine Atlanta, Georgia

References 1. Goulet O, Ruemmele F, Lacaille F, Colomb V. Irreversible intestinal failure. J Pediatr Gastroenterol Nutr 2004;38:250 –269. 2. Wilmore DW, Dudrick SJ. Growth and development of an infant receiving all nutrients exclusively by vein. JAMA 1968;203:860 – 864. 3. Dudrick SJ, Wilmore DW, Vars HM, Rhoads JE. Can intravenous feeding as the sole means of nutrition support growth in the child and restore weight loss in an adult? An affirmative answer. Ann Surg 1969;169:974 –984. 4. Jeejeebhoy KN, Zohrab WJ, Langer B, et al. Total parenteral nutrition at home for 23 months, without complications and with good rehabilitation. Gastroenterology 1973;65:811– 820.

February Supplement 2006

5. Broviac JN, Scribner BH. Prolonged parenteral nutrition in the home. Surg Gynecol Obstret 1974;139:24 –28. 6. Carbonnel R, Cosnes J, Chevret S, Beaugerie L, Ngo Y, Malafosse M, Parc R, Le Quintrec Y, Gendre JP. The role of anatomic factors in nutritional autonomy after extensive small bowel resection. J Parenter Enteral Nutr 1996;20:275–280. 7. Messing B, Crenn P, Beau P, Boutron-Ruault MC, Rambaud JC, Matuchansky C. Long-term survival and parenteral nutrition dependence in adult patients with the short bowel syndrome. Gastroenterology 1999;117:1043–1050. 8. Quiros-Tejeira RE, Ament ME, Reyen L, Herzog F, Merjanian M, Olivares-Serrano N, Vargas JH. Long-term parenteral nutritional support and intestinal adaptation in children with short bowel syndrome: a 25-year experience. J Pediatr 2004;145:157–163. 9. Byrne TA, Persinger RL, Young LS, Ziegler TR, Wilmore DW. A new treatment for patients with short-bowel syndrome. Growth hormone, glutamine, and a modified diet. Ann Surg 1995;222:243– 254. 10. Wilmore DW, Lacey JM, Soultanakis RP, Bosch RL, Byrne TA. Factors predicting a successful outcome after pharmacologic bowel compensation. Ann Surg 1997;226:288 –292. 11. Ziegler TR, Evans ME, Fernandez-Estivariz C, Jones DP. Trophic and cytoprotective nutrition for intestinal adaptation, mucosal repair, and barrier function. Annu Rev Nutr 2003;23:229 –261. 12. DiBaise JK, Young RJ, Vanderhoof JA. Intestinal rehabilitation and the short bowel syndrome: part 1. Am J Gastroenterol 2004; 99:1386 –1395. 13. Vanderhoof JA. New and emerging therapies for short bowel syndrome in children. J Pediatr Gastroenterol Nutr 2004;39: S769 –771. 14. Wilmore DW, Dudrick SJ, Daly JM, Vars HM. The role of nutrition in the adaptation of the small intestine after massive resection. Surg Gynecol Obstet 1971;132:673– 680. 15. Jeejeebhoy KN. Management of short bowel syndrome: avoidance of TPN. Gastroenterology 2006;130(Suppl 1):S60 –S66. 16. Messing B, Joly F, Badran AM. Guidelines for management of home parenteral support in adult chronic intestinal failure. Gastroenterology 2006;130(Suppl 1):S43–S51. 17. Howard L. Home parenteral nutrition: survival, cost and quality of life. Gastroenterology 2006;130(Suppl 1):S52–S59. 18. Althausen TL, Doig RK, Uyeyama K. Digestion and absorption after massive resection of small intestine; recovery of absorptive function as shown by intestinal absorption tests in 2 patients and consideration of compensatory mechanisms. Gastroenterology 1950;16:126 –139. 19. O’Keefe SJ, Haymond MW, Bennet WM, Oswald B, Nelson DK, Shorter RG. Long-acting somatostatin analogue therapy and protein metabolism in patients with jejunostomies. Gastroenterology 1994;107:379 –388. 20. Ziegler TR, Estivariz CF, Gu LH, Wallace TM, Díaz EE, Pascal RR, Bazargan N, Galloway JR, Wilcox JN, Leader LM. Distribution of the H⫹/peptide transporter PepT1 in human intestine: up-regulated expression in the colonic mucosa of patients with short bowel syndrome. Am J Clin Nutr 2002;75:922–930. 21. Shin ED, Estall JL, Izzo A, Drucker DJ, Brubaker PL. Mucosal adaptation to enteral nutrients is dependent on the physiologic actions of glucagon-like peptide-2 in mice. Gastroenterology 2005;128:1340 –1453. 22. Levy E, Frileux P, Sandrucci S, Ollivier JM, Masini JP, Cosnes J, Hannoun L, Parc R. Continuous enteral nutrition during the early adaptive stage of the short bowel syndrome. Br J Surg 1988;75: 549 –553. 23. Crenn P, Morin MC, Joly F, Penven S, Thuillier F, Messing B. Net digestive absorption and adaptive hyperphagia in adult short bowel patients. Gut 2004;53:1279 –1286. 24. Nauth J, Chang CW, Mobarhan S, Sparks S, Borton M, Svoboda S. A therapeutic approach to wean total parenteral nutrition in the

EDITORIAL

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35. 36. 37.

38.

39.

40.

41.

42.

S41

management of short bowel syndrome: three cases using nocturnal enteral rehydration. Nutr Rev 2004;62:221–231. Royall D, Wolever TM, Jeejeebhoy KN. Evidence for colonic conservation of malabsorbed carbohydrate in short bowel syndrome. Am J Gastroenterol 1992;87:751–756. Byrne TA, Veglia LM, Camelio M, Cox S, Anderson S, Wilson J, Bennett HM. Beyond the prescription: optimizing the diet of patients with short bowel syndrome. Nutr Clin Pract 2000;15: 306 –311. Ovesen L, Chu R, Howard L. The influence of dietary fat on jejunostomy output in patients with severe short bowel syndrome. Am J Clin Nutr 1983;38:270 –277. Fernandez-Estívariz C, Umeakunne K, Bazargan N, Galloway JR, Leader LM, Ziegler TR. Oral nutrient intake in patients with severe short bowel syndrome living in the United States (abstr). JPEN J Parent Enteral Nutr 2003;27:S25. McDoniel K, Taylor B, Huey W, Eiden K, Everett S, Fleshman J, Buchman TG, Alpers D, Klein S. Use of clonidine to decrease intestinal fluid losses in patients with high-output short-bowel syndrome. JPEN J Parenter Enteral Nutr 2004;28:265–268. D’Antiga L, Dhawan A, Davenport M, Mieli-Vergani G, Bjarnason I. Intestinal absorption and permeability in paediatric short-bowel syndrome: a pilot study. J Pediatr Gastroenterol Nutr 1999;29: 588 –593. Terra RM, Plopper C, Waitzberg DL, Cukier C, Santoro S, Martins JR, Song RJ, Gama-Rodrigues J. Remaining small bowel length: association with catheter sepsis in patients receiving home total parenteral nutrition: evidence of bacterial translocation. World J Surg 2000;24:1537–1541. Buchman AL, Moukarzel A, Goodson B, Herzog F, Pollack P, Reyen L, Alvarez M, Ament ME, Gornbein J. Catheter-related infections associated with home parenteral nutrition and predictive factors for the need for catheter removal in their treatment. JPEN J Parenter Enteral Nutr 1994;18:297–302. Ziegler TR, Estivariz CF, Luo M, Gu LH, Sitaraman SV, Klapproth J-M, Leader LM, Gewirtz AT. Patients with short bowel syndrome exhibit a high incidence of detectable flagellin and lipopolysaccharide (LPS) and markedly elevated flagellin-specific immunoglobulins in serum. Gastroenterology 2005;128(Suppl 2): A665(abst). Kaufman SS, Loseke CA, Lupo JV, Young RJ, Murray ND, Pinch LW, Vanderhoof JA. Influence of bacterial overgrowth and intestinal inflammation on duration of parenteral nutrition in children with short bowel syndrome. J Pediatr 1997;131:356 –361. Desai AA, Toskes PP. Bacterial overgrowth syndrome. Curr Treat Options Inf Dis 2003;5:189 –196. Saltzman JR, Russell RM. Nutritional consequences of intestinal bacterial overgrowth. Compr Ther 1994;20:523–530. Reid G, Jass J, Sebulsky MT, McCormick JK. Potential uses of probiotics in clinical practice. Clin Microbiol Rev 2003;16:658 – 672. Uchida H, Yamamoto H, Kisaki Y, Fujino J, Ishimaru Y, Ikeda H. D-lactic acidosis in short-bowel syndrome managed with antibiotics and probiotics. J Pediatr Surg 2004;39:634 – 636. Kunz AN, Noel JM, Fairchok MP. Two cases of Lactobacillus bacteremia during probiotic treatment of short gut syndrome. J Pediatr Gastroenterol Nutr 2004;38:457– 460. De Groote MA, Frank DN, Dowell E, Glode MP, Pace NR. Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. Pediatr Infect Dis J 2005; 24: 278 –280. Seguy D, Vahedi K, Kapel N, Souberbielle JC, Messing B. Lowdose growth hormone in adult home parenteral nutrition-dependent short bowel syndrome patients: a positive study. Gastroenterology 2003;124:293–302. Byrne TA, Wilmore DW, Iyer K, Dibaise J, Clancy K, Robinson MK, Chang P, Gertner JM, Lautz D. Growth hormone, glutamine, and

S42

43.

44.

45.

46.

47.

48.

49.

50.

EDITORIAL

an optimal diet reduces parenteral nutrition in patients with short bowel syndrome: a prospective, randomized, placebo-controlled, double-blind clinical trial. Ann Surg 2005;242:655– 661. Weiming Z, Ning L, Jieshou L. Effect of recombinant human growth hormone and enteral nutrition on short bowel syndrome. JPEN J Parenter Enteral Nutr 2004; 28:377–381. Ladd AP, Grosfeld JL, Pescovitz OH, Johnson NB. The effect of growth hormone supplementation on late nutritional independence in pediatric patients with short bowel syndrome. J Pediatr Surg 2005;40:442– 445. Jeppesen PB, Hartmann B, Thulesen J, Graff J, Lohmann J, Hansen BS, Tofteng F, Poulsen SS, Madsen JL, Holst JJ, Mortensen PB. Gastroenterology 2001;120:806 – 815. Jeppesen PB, Sanguinetti EL, Buchman A, Howard L, Scolapio JS, Ziegler TR, Gregory J, Tappenden KA, Holst J, Mortensen PB. Teduglutide (ALX-0600), a dipeptidyl peptidase-IV resistant glucagon-like peptide-2 analog, improves intestinal function in short bowel syndrome patients. Gut 2005;(in press). Washizawa N, Gu LH, Gu L, Openo KP, Jones DP, Ziegler TR. Comparative effects of glucagon-like peptide-2 (GLP-2), growth hormone (GH), and keratinocyte growth factor (KGF) on markers of gut adaptation after massive small bowel resection in rats. JPEN J Parenter Enteral Nutr 2004;28:399 – 409. Nightingale JM. Hepatobiliary, renal and bone complications of intestinal failure. Best Pract Res Clin Gastroenterol 2003;17: 907–929. Howard L, Ashley C. Management of complications in patients receiving home parenteral nutrition. Gastroenterology 2003;124: 1651–1661. Cavicchi M, Beau P, Crenn P, Degott C, Messing B. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med 2000;132:525–532.

GASTROENTEROLOGY Vol. 130, No. 2

51. Crenn P, Vahedi K, Lavergne-Slove A, Cynober L, Matuchansky C, Messing B. Plasma citrulline: a marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology 2003;124:1210 –1219. 52. Rhoads JM, Plunkett E, Galanko J, Lichtman S, Taylor L, Maynor A, Weiner T, Freeman K, Guarisco JL, Wu GY. Serum citrulline levels correlate with enteral tolerance and bowel length in infants with short bowel syndrome. J Pediatr 2005;146:542–547. 53. Sigalet DL, Martin G, Meddings J, Hartman B, Holst JJ. GLP-2 levels in infants with intestinal dysfunction. Pediatr Res 2004; 56:371–376. 54. Jeppesen PB, Langholz E, Mortensen PB. Quality of life in patients receiving home parenteral nutrition. Gut 1999;44:844 – 852. 55. Winkler MF. Quality of life in adult home parenteral nutrition patients. JPEN J Parent Enteral Nutr 2005;29:162–170. 56. Oley Foundation for Home Parenteral and Enteral Nutrition, 214 Hun Memorial, MC 28, Albany Medical College, Albany, NY 12208. www.oley.org.

Address requests for reprints to: Thomas R. Ziegler, MD, General Clinical Research Center, Room GG-23, Emory University Hospital, 1364 Clifton Road, Atlanta, Georgia 30322. e-mail [email protected]; fax: (404) 727-5563. Supported by National Institutes of Health grants R01 DK55850, R03 DK67123, and General Clinical Research Center grant M01 RR00039. © 2006 by the American Gastroenterological Association 0016-5085/06/$32.00 doi:10.1053/j.gastro.2005.09.063