Adaptation In Short Bowel Syndrome Research Articles

Etiology and Initial Management of Short Bowel Syndrome

o he normal human small intestine ranges between 3 and 8 m in length, depending on whether measureent is made by radiologic or surgical techniques or at utopsy when the intestine may be desicated.1–5 Short owel syndrome is defined in adults as 200 cm of small ntestine. Although usually acquired because of one or ore enterectomies, short bowel syndrome may also be ongenitally acquired. Nutrient, electrolyte, and fluid bsorption is proportional to the amount of residual ntestine. The degree of intestinal function is better escribed in terms of energy absorption/loss rather than ength of residual intestine.6 Intestinal failure may be efined as the inability to sustain adequate nutritional, lectrolyte, or hydrational status in the absence of speialized nutritional support. This requires an increase in ral intake because absorption is compromised. Clinially, nutrient assimilation is a function of intake and bsorption. As such, some patients with short bowel yndrome will not have sufficient loss of functional caacity as to develop intestinal failure. Significant indiidual variability in jejunal absorption efficiency may be ncountered.7 The patients with the greatest risk for development of ehydration, generalized protein-calorie malnutrition, nd multiple nutrient deficiencies are those with a duoenostomy or jejunoileal anastomosis and 35 cm of esidual small intestine; jejunocolic or ileocoloic anastoosis, and 60 cm of residual small intestine; or end ejunostomy with 115 cm of residual small intesine.6,8–11 Those patients with residual colon in continuty will have enhanced energy and fluid absorption. ence, such patients can tolerate greater loss of small ntestine and retain their nutritional autonomy.

Intestinal Replacement Therapy: Timing and Indications for Referral of Patients to an Intestinal Rehabilitation and Transplant Program

Current treatment options for patients suffering from intestinal insufficiency include all forms of intestinal replacement therapy (IRT). Parenteral nutrition has achieved extended success for the majority of patients requiring interval treatment, however, complications leading to failure of this treatment increases with the duration of therapy. There is currently no consensus as to the appropriate timing for transplantation of the intestine or the timing of referral for evaluation at a center experienced with this therapy. Certain patient characteristics warrant evaluation. Those patients with no jejunoileum who have guaranteed lifelong parenteral dependence, both adult and pediatric, should be immediately referred to a transplant center due to the high likelihood of the development of liver disease. Patients with metastatic infectious complications from catheter sepsis, patients with cholestasis seen intermittently with sepsis episodes, patients who are not successfully weaning and who demonstrate progressive thrombocytopenia, and patients with motility disorder experiencing deterioration should also warrant early referral to an intestinal rehabilitation and transplant program. The objective of evaluation is to maximize the opportunities for rehabilitation while not missing the critical window of opportunity for successful transplantation when needed. We favor an aggressive directed approach to rehabilitation, coupled with psychological preparation for both transplantations and other options. Early referral requires trust between the patient, referring physician, and the transplant team to assure that a rush to judgment will not lead to a premature transplant. The current wait list mortality is high, mandating early referral and listing with an approach aimed at maximizing both the success of gastrointestinal support, as well as of transplantation when necessary.

Intestinal intraepithelial lymphocyte derived angiotensin converting enzyme modulates epithelial cell apoptosis

Intestinal adaptation in short bowel syndrome (SBS) consists of increased epithelial cell (EC) proliferation as well as apoptosis. Previous microarray analyses of intraepithelial lymphocytes (IEL) gene expression after SBS showed an increased expression of angiotensin converting enzyme (ACE). Because ACE has been shown to promote alveolar EC apoptosis, we examined if IEL-derived ACE plays a role in intestinal EC apoptosis. Mice underwent either a 70% mid-intestinal resection (SBS group) or a transection (Sham group) and were studied at 7 days. ACE expression was measured, and ACE inhibition (ACE-I, enalaprilat) was used to assess ACE function. IEL-derived ACE was significantly elevated in SBS mice. The addition of an ACE-I to SBS mice resulted in a significant decline in EC apoptosis. To address a possible mechanism, tumor necrosis factor alpha (TNF-alpha) mRNA expression was measured. TNF-alpha was significantly increased in SBS mice, and decreased with ACE-I. Interestingly, ACE-I was not able to decrease EC apoptosis in TNF-alpha knockout mice. This study shows a previously undescribed expression of ACE by IEL. SBS was associated with an increase in IEL-derived ACE. ACE appears to be associated with an up-regulation of intestinal EC apoptosis. ACE-I significantly decreased EC apoptosis.

Effect of glutamine and growth hormone on adaptation in short bowel syndrome

To assess the effects of parenteral glutamine and growth hormone supplementation on gut adaptation for patients with short bowel syndrome. Twenty-six patients [male 15, female 11, aged (39 +/- 23) years] with short bowel syndrome received parenteral nutrition (PN) 3-52 months after surgical resection. The median length of remnant small intestine was 42.5(0-100)cm. All patients received growth hormone (0.10+/- 0.06) mg.kg(-1).d(-1) plus glutamine (0.30 +/- 0.17) mg.kg(-1).d(-1) for two or three weeks. Among the 26 patients, PN was not required soon after treatment in 34.6% (n=9) of the patients, the frequency and volume of PN decreased from (6.0 +/- 1.0) d to (4.2 +/- 1.0) d, from (13.6 +/- 5.2) L per week to (8.2 +/- 3.3) L per week respectively in 30.8% (n=8) of the patients,while 34.6% (n=9) still required PN after treatment. The combined administration of glutamine and growth hormone can promote remnant intestinal adaptation in short bowel patients.

Adverse effects of liver dysfunction and portal hypertension on intestinal adaptation in short bowel syndrome in children

BackgroundThe effects of liver dysfunction and portal hypertension on intestinal adaptation in short bowel syndrome are generally unknown. The presence of these disorders may adversely affect the ability to wean these patients from parenteral nutrition. Methods:Forty-two infants with short bowel syndrome were placed in one of three Child’s classifications, depending on serum bilirubin, prothrombin time, ascites, albumin, and liver biopsy, and compared for time to diet tolerance, time required for parenteral nutrition, and survival. A subgroup of these patients also underwent portal pressure measurement, which was combined with liver biopsy results to compare three groups for the same parameters. Results:Survival was Child’s class A 100%, B 84%, C 61%, while time to feeding tolerance was A 16.3 days, B 20.0 days, C 28 days, and total parenteral nutrition time was A 80.0 days, B 98.0 days, C 100.0 days. In the groups that underwent portal pressure measurement, the survival was group I (normal biopsy and pressure) 100%, group II (abnormal biopsy and normal pressure) 90%, group III (abnormal biopsy and pressure) 66%, while time to feeding tolerance was I 15.0 days, II 18.0 days, III 24.0 days, and total parenteral nutrition time was I 72.0 days, II 94.0 days, III 184.0 days. ConclusionsCholestatic liver disease, especially associated with portal hypertension adversely affects bowel adaptation in short bowel syndrome.

Enhancing bowel adaptation in short bowel syndrome.

Malabsorption of both nonessential and essential nutrients, fluid, and electrolytes will, if not compensated for by increased intake, lead to diminished body stores and to subclinical and eventually clinical deficiencies. By definition, intestinal failure prevails when parenteral support is necessary to maintain nutritional equilibrium. After intestinal resection, adaptation, a progressive recovery from the malabsorptive disorder, may be seen. Research has focused on optimizing remnant intestinal function through dietary or pharmacologic interventions. In this review, factors responsible for the morphologic and functional changes in the adaptive processes are described. Results of clinical trials employing either growth hormone and glutamine or glucagon-like peptide-2 in short bowel patients are presented.

Intestinal adaptation in short-bowel syndrome in infants and children: a collective review.

Intestinal adaptation in short-bowel syndrome in infants and children: a collective review.

Intestinal adaptation in short bowel syndrome.

Regaining enteral autonomy after extensive small bowel resection is dependent on intestinal adaptation. This adaptational process is characterized by hyperplastic growth of the remaining gut, which is accompanied by both an increase of cell division at the level of the crypt cells and by an increased rate of programmed cell death (apoptosis). Apart from the absorptive function, the small bowel also has a barrier function and plays an important role in interorgan metabolism. Also, these functions are greatly affected by a massive intestinal resection and subsequent recovery by intestinal adaptation. This review aims to give an overview of the debilitating effects of massive intestinal resection on gut function and subsequently discusses intestinal adaptation and possible factors stimulating adaptation.

Differential sugar absorption as a marker for adaptation in short bowel syndrome

Purpose: There are no reliable monitoring methods for following up with patients with short bowel syndrome (SBS). This study examines the use of inert sugar markers (mannitol and lactulose) as indicators of the surface area increases occurring with adaptation. Methods: Juvenile male rats underwent either transection with intestinal reanastomosis or resection with removal of the proximal 90% of the small bowel, leaving 10 cm of terminal ileum (n = 8 in each group). Animals were studied in vivo, measuring absorption of mannitol and lactulose on day 7, 14, and 28 and killed with the representative histological samples taken on day 7, 14, and 28. Results: Resected animals showed significant increases in intestinal length (initial bowel length 10 cm, final length 17.8 ± 1.4 cm, while transected showed no significant changes (101 ± 2 cm): resection also increased intestinal circumference (initial circumference 0.5 cm ± 0.1 cm, final circumference 1.1 cm ± 0.2 cm in resected animals, while transected animals remained unchanged). Resected animals also showed significant increases in villus height (0.7 ± 0.06 mm initially, 0.9 ± 0.09 mm at day 28), and but a decrease in villus density (116 ± 20 villi/mm2 initially, 78 ± 20 villi/mm2 at day 28), again controls showed no changes. This resulted in a significant increase in intestinal surface area in resected animals over the study; surface area initially calculated at 640 ± 80 cm2 increasing to 1,440 ± 360 cm2, while controls showed no significant change in surface area. There was also an increase in mannitol absorption, which went from 1.8 ± 0.6% on day 7 to 2.56 ± 0.6% on day 28 in resected animals, while permeability actually decreased over time. (All data mean ± SD, with P <.05 by Student's t test). Mannitol absorption correlated well with intestinal surface area (R2 = 0.82). Conclusion: These results suggest that inert sugar markers, such as lactulose and mannitol, may be useful in following adaptation in patients who have short bowel syndrome. J Pediatr Surg 35:661-664. Copyright © 2000 by W.B. Saunders Company.

Effect of growth hormone on bacterial translocation in experimental short-bowel syndrome.

Despite the adaptive process triggered in the remaining intestine by massive bowel resection, bacterial translocation (BT) is frequent under these conditions. Several trophic factors, including growth hormone (GH), are involved in the process of adaptation in short-bowel syndrome (SBS). However, the effect of GH on BT has not been investigated experimentally. The aim of this study was to test the hypothesis that GH administration prevents BT in rats with SBS receiving only parental nutrition (PN). Nineteen adult Wistar rats underwent central venous cannulation and were randomly assigned to one of two groups receiving for 10 days two treatment regimes: PN group (n = 10): fasting, all-in-one PN solution (300 ml. kg. 24 h, 280 kcal/kg. 24 h), 80% gut section including ileocecal valve; GH group (n = 9): fasting, same PN regime and resection plus GH 1 mg/kg s.c). At the end of the experiment, the rats were killed and mesenteric lymph nodes (MLN) and samples of systemic and portal blood were obtained and cultured. Several samples of full-thickness jejunal wall were taken for determining cell proliferation index (PCNA) and mucosal thickness. Jejunal mucosal thickness increased by 30% and PCNA index by 35% in GH-treated rats in comparison with those treated with PN alone. However, contrary to our expectations, BT expressed by positive culture of intestinal flora in portal blood, MLN, or systemic blood was found in 60% of PN and 87% of GH animals (P = 0.1). Translocation to the general circulation expressed by the presence of organisms in systemic blood was detected in 0% of PN and 44% of GH rats (P < 0.05). Although exogenous GH improves gut mucosal structure in rats with SBS treated with PN, it seems to increase rather than decrease mucosal permeability to intestinal bacteria.

Dietary lipids influence intestinal adaptation after massive bowel resection.

Certain lipids, primarily long chain fatty acids and especially long chain polyunsaturated fatty acids (LCPUFAs) from marine oils, stimulate gut adaptation after resection. The goal of this study was to define the degree of resection that provides an optimal model for adaptation and to determine if dietary LCPUFAs improve intestinal adaptation after resection. One hundred and fifty-g male Sprague-Dawley rats were divided into groups receiving 60%, 70%, and 80% bowel resection. After resection, each group was subdivided into two dietary groups and pair fed diets containing either safflower oil or docosahexaenoic acid (DHA) and arachidonic (AA). After 2 weeks, mucosal mass, protein, DNA, and disaccharidase activity were measured in the remaining intestine. Rats receiving 80% resection responded with the highest level of intestinal adaptation. Within the 80% resection group, diet containing DHA and AA stimulated adaptation significantly more than safflower diet. A second study further evaluated the effect on LCPUFAs on intestinal adaptation. Diets included a control group 10% soy oil, and three diets differing in their AA-DHA fat blend ratio at 5% AA and 3.3% DHA, 15% AA and 10% DHA, and 45% AA and 30% DHA. The addition of LCPUFAs to diets enhanced intestinal adaptation in a linear, dose-dependent manner after an 80% small bowel resection. Rats fed a diet containing 30% DHA-45% AA had significantly enhanced mucosal mass compared to rats fed a diet containing 10% soy oil, and considerably higher compared to rats fed 3.3% DHA-5% AA. These studies suggest that modification of dietary LCPUFAs may enhance intestinal adaptation in short bowel syndrome.

Effect of growth hormone, glutamine, and diet on adaptation in short-bowel syndrome: A randomized, controlled study: J.S. Scolapio, M. Camilleri, C.R. Fleming, et al. Gastroenterology 113:1074–1081 (October), 1997

Effect of growth hormone, glutamine, and diet on adaptation in short-bowel syndrome: A randomized, controlled study: J.S. Scolapio, M. Camilleri, C.R. Fleming, et al. Gastroenterology 113:1074–1081 (October), 1997

Lack of inhibitory effect of octreotide on intestinal adaptation in short bowel syndrome in the rat.

Octreotide is a long-acting analogue of somatostatin, which is effective in the treatment of secretory diarrhea in a number of disorders including short bowel syndrome. Its use in this syndrome has been limited because of concerns about potential adverse effect on intestinal adaptation, because it inhibits a number of trophic hormones. This study was conducted to determine whether octreotide inhibits intestinal adaptation in a rat model of short bowel syndrome. Thirty male Sprague-Dawley rats were divided into four treatment groups, eight receiving 80% small-bowel resection and treated with 2.25 microg/kg(-1) per day(-1) of octreotide, eight receiving 80% small-bowel resection and treated with 25 microg/kg(-1) per day(-1) of octreotide, eight receiving 80% small-bowel resection with saline control, and six receiving sham operation with saline control. Mucosal weight, protein, and sucrase levels were subsequently analyzed after 2 weeks of therapy. Massive adaptation occurred in all three groups relative to sham-operated controls. However, neither the pharmacologic nor the much higher dose of octreotide demonstrated any adverse effects on intestinal adaptation. In our animal model, octreotide does not inhibit intestinal adaptation after massive small-bowel resection.

Effect of growth hormone, glutamine, and diet on adaptation in short- bowel syndrome: A randomized, controlled study

BACKGROUND & AIMS: The effects of parenteral growth hormone, glutamine supplementation, and a high carbohydrate-low fat (HCLF) diet on gut adaptation in short-bowel syndrome are unclear. The aim of this study was to compare effects of this treatment regimen and placebo in patients with short-bowel syndrome.METHODS: A randomized, 6-week, double-blind, placebo-controlled, crossover study in 8 patients with short-bowel syndrome (average small bowel length, 71 cm; mean duration, 12.9 years) was performed. Active treatment was growth hormone (0.14 mg.kg-1.day-1), oral glutamine (0.63 g.kg-1.day-1), and the HCLF diet for 21 days. The weight, basal metabolic rate, nutrient and electrolyte balance, serum insulin-like growth factor I levels, D-xylose absorption, morphology and DNA proliferation of small intestinal mucosa, and gastrointestinal transit were evaluated. Treatments were compared by paired t test.RESULTS: Active treatment transiently increased body weight, significantly but modestly increased the absorption of sodium and potassium, and decreased gastric emptying. The assimilation of macronutrients, stool volumes, and morphometry of small bowel mucosa were not statistically different in the two treatment arms.CONCLUSIONS: Although treatment with growth hormone, glutamine, and HCLF diet for 3 weeks resulted in modest improvements in electrolyte absorption and delayed gastric emptying, there were no improvements in small bowel morphology, stool losses, or macronutrient absorption.(Gastroenterology 1997 Oct;113(4):1074-81)

Intestinal adaptation in short bowel syndrome

Short bowel syndrome (SBS) either in adults or in children is considered as an indication of small bowel transplantation (SBT). 1,2 Severity and prognosis depend on various factors such as small bowel resection length, patient's age, and intestinal length at the time of resection. In pediatrics, most patients, affected by SBS undergo resection when neonates or anyway in the first months of life (necrotizing enterocolitis, congenital anomalies of gastrointestinal troct, abdominal wall defects); only in few patients pathology begins later on, usually for tumoral, vascular or Crohn's diseases. Intestinal adaptation process, characterized by epithelial hyperplasia, has an early onset, within the first days after resection, with a progressive increase of intestinal absorptive surface; such adapting capacity is greater for ileum rather than for jejunum. 2–5 This intestinal adaptation process with mucosal hyperplasia requires an enteral nutrition which acts both directly by nutrients contact on intestinal epithelium and by stimulating the secretion of trophic factors such as enteroglucagon, epidermal growth factor and insulin-like growth factor-1. From the clinical point of view, the term “adaptation” means the total nutritional autonomy with a satisfying height and weight growth. In patients who initially need parenteral nutrition (PN), total intestinal adaptation is considered as attained when they can stop PN. The aim of the present study is to evaluate retrospectively our series of severe SBS patients, with residual intestine shorter than 100 cm, who consequently required a prolonged PN, verifying the possibility and the time of intestinal adaptation and therefore the existence or not of an indication to intestinal transplantation.

Human Growth Hormone Induces System B Transport in Short Bowel Syndrome

Background: After massive enterectomy, remnant intestine undergoes compensatory adaptation. A combination of human growth hormone (hGH) and a glutamine-enriched modified diet induces further adaptation in patients with short bowel syndrome (SBS) on long-term total parenteral nutrition. The specific actions of each component, however, are not well-defined. Methods: New Zealand White rabbits were randomized to control, sham operation, or SBS (70% midjejunoileal resection) groups and treated with either hGH or saline. Sodium-dependent uptake of glucose, glutamine, alanine, leucine, and arginine into brush border membrane vesicles was quantitated. Serum insulin-like growth factor-I (IGF-I) levels were determined by immunoradiometric assay. Mucosal mRNA expression of IGF-I and IGF binding protein 4 (IGFBP-4) was evaluated by Northern blot analysis using rat cDNA probes. Results: Glutamine and leucine transports were 33 and 39% greater, respectively, in the hGH-treated versus saline-treated SBS group (P< 0.05), supporting induction of system B amino acid transport. This upregulation was due, in part, to an 88% increase in glutamine carrier capacity (Vmax) with no change in carrier affinity (Km). Both hGH treatment and SBS increased serum IGF-I levels without direct correlation with increased nutrient transport. IGFBP-4 mRNA expression in small bowel mucosa of saline-treated SBS animals was significantly greater than saline-treated unoperated control values. Mucosal IGFBP-4 mRNA was not significantly altered from control in the other study groups. IGF-I mRNA expression was not detected in mucosa, but weak hybridization was noted in rabbit liver. Conclusions: Human growth hormone accelerates early adaptation in SBS by upregulation of system B carrier capacity. Serum IGF-I levels and mucosal IGF-I and IGFBP-4 mRNA expression did not directly correlate with this enhanced nutrient transport, suggesting that hGH might exert its adaptive effects by mechanisms that are independent from the IGF system in this model.

DIETARY LIPIDS INFLUENCE GUT ADAPTATION FOLLOWING RESECTION.

Certain lipids, primarily long chain fats and especially highly unsaturated long chain fats from marine oil stimulate gut adaptation following resection. We evaluated the effects of 2 diets with different lipid composition on mucosal adaptation. Forty 150 g male Sprague-Dawley rats were divided into groups receiving 80%, 70% and 60% small bowel resections to determine the appropriate degree of resection that results in the greatest differences in adaptation. Rats were further divided into 2 dietary groups and pair fed diets, 1 predominantly safflower oil, the other contained both docosahexaenoic acid (DHA) and arachidonic acid (AA). All diets contained 30% of their calories from fat. After 2 weeks, mucosal mass, protein, DNA and disaccharidase levels were measured in the remaining small intestine, both proximal and distal to the anastomosis. Rats receiving 80% resection significantly provided the highest levels of adaptation when compared to the other resection lengths. Studies using the 80% resection model revealed that DHA and AA stimulated adaptation significantly more than safflower oil, a good source of linoleic acid. These studies suggest that modification of dietary lipids may enhance gut adaptation in short bowel syndrome. Figure

Enteral feeding increases sepsis in infants with short bowel syndrome

Sepsis secondary to bacterial translocation is common in infants with short bowel syndrome (SBS). Although early feeding is advocated to enhance adaptation in SBS, the effects of feeding on sepsis in SBS patients have not been examined. Twenty-one infants and children (aged 2 months to 3 years) with SBS (<80 cm small bowel length) from a variety of causes (15 necrotizing enterocolitis, 2 atresia, 2 gastroschisis, 2 volvulus) had follow-up prospectively for septic episodes before and after feedings were initiated, while still receiving total parenteral nutrition. The incidence and number of septic episodes and microbiology (blood cultures) were tabulated and compared with those of 20 patients with similar ages, and diagnoses without SBS. Statistically significant differences among infants with SBS were noted with respect to sepsis incidence (6 of 21 [29%] NPO v 16 of 21 [76%] feeding) number of septic episodes (1.3 ± .2 NPO v 4.2 ± .4 feeding), and presence of gramnegative rods causing bacteriemia (1 of 6 [17%] NPO v 13 of 16 [81%] feeding) (all: P < .05). There were similar differences between SBS and non-SBS infants. These data show that enteral feeding increases the incidence and number of episodes of sepsis in SBS infants, but not in matched non-SBS patients. The predominance of gram-negative organisms in sepsis in SBS suggests increased gut bacterial translocation in these patients, implying that selective gut decontamination may reduce the episodes of bacteremia.

Donʼt expect too much of intestinal adaptation in short bowel syndrome

Donʼt expect too much of intestinal adaptation in short bowel syndrome

Adaptation in short-bowel syndrome: Reassessing old limits

The improving survival of patients with severe short-bowel syndrome along with the advent of successful intestinal transplantation have accentuated the need to answer two questions. (1) Is there an intestinal length below which adaptation to full enteral nutrition can not be expected to occur? (2) How much time is necessary to complete intestinal adaptation? We reviewed the outcome of 21 infants with less than 50 cm of small intestine to answer these questions. Patients were divided into three groups based on intestinal length, regardless of ileocecal valve status: group I, <10 cm (n = 3); group II, 10 to 30 cm (n = 11); and group III, 30 to 50 cm (n = 7). Data were collected to assess survival, incidence of adaptation, time to adaptation, and causes of mortality. Infants in group I did not achieve intestinal adaptation to full enteral nutrition. One survived and 2 died, one from varicella pneumonia and the other after intestinal transplantation. Eight of the 11 (73%) patients in group II survived and 5 of 8 (63%) survivors achieved full intestinal adaptation after a mean interval of 320 days (range, 148 to 506 days) on parenteral nutrition. Six of the seven patients (86%) in group III survived and all survivors (100%) achieved complete enteral adaptation after an average of 376 days (range, 58 to 727 days). The overall survival was 71% ( 15 21 ), but survival in patients with > 10 cm was 78%. The incidence of fatal catheter sepsis ( 2 21 ) and fatal parenteral nutrition-associated liver failure ( 1 21 ) was low and accounted for two of the six deaths—one patient died as a consequence of both complications. The 10-cm small intestinal length appears to be a new lower limit for the length necessary to achieve enteral nutrition. Patients with > 10 cm of small intestine should be supported on parenteral nutrition with early institution of enteral feedings to promote intestinal adaptation for a minimum of 2 years before transplantation is considered.