The management of patients with the short bowel syndrome

Table 1 The effect of small bowel resection on intestinal peptides that are known regulate intestinal growth

Factor	Source	Effect of Small Bowel Resection on Factor
Epidermal Growth	Salivery glands and Brunner’s glands in the jejunum	EGF levels are increased in saliva and diminished in urine 3 d after resection in mice[11].
Factor (EGF)
Enteroglucagon	L cells of ileum and colon	12 d after a 75% small bowel resection there was a significant increase in concentration of enteroglucagon in the plasma of rats[12].
Glucagon-like	L cells of ileum and colon	There is an increase in expression of GLP-2 mRNA in the ileum of rats after small bowel resection[13].
Peptide 2 (GLP-2)
		There is a decrease in expression of dipeptidyl peptidase IV mRNA, the enzyme that inactivates GLP-2, in the ileum of rats after small bowel resection[14].
Insulin-like Growth	Cells of the small	80% small bowel resection led to a 183% and 249% increase in IGF-1 mRNA in the jejunum and ileum respectively of rats[15].
factor-1 (IGF-1)	intestine
Peptide tyrosine	L cells of ileum	After 70% resection in rats the concentration of PYY in plasma was elevated for at least 2 wk and there was a
tyrosine (PYY)		four and six-fold increase in PYY mRNA in ileum and colon at six hours after resection[14].
Neurotensin	Gut mucosal endocrine cells
	(N cells) in the jejunum and ileum	50% resection of the distal intestine in dogs was associated with a transient increase in neurotensin[16].

Table 2 Nutrients that regulate gut adaptation

Nutrient	Effect on Intestinal Adaptation
Soluble fibre and short	SCFA-supplemented parenteral nutrition led to an increase in ileal uptake of D-glucose in rats with an 80% small bowel resection[28].
chain fatty acids
	A 2% pectin-enriched elemental diet led to a significant increase in intestinal weight, mucosal protein content, and mucosal DNA
	content in rats with an 80% small bowel resection[29].
Triglycerides	Rats fed with an elemental diet containing 60% long chain triglycerides after a 60% resection had a greater intestinal adaptation than
	rats fed a diet containing 17% long chain triglycerides[30].
Ornithine	Enteral supplements of ornithine 2g·kg-1·d-1 significantly increased jejunal crypt depth ratio and significantly increased glutamine
α -ketoglutarate	concentration in anterior tibialis muscle[31].
	Enteral supplements of ornithine 1 g·kg-1·d-1 significantly increased ileal villus height and expression of ornithine decarboxylase mRNA
	in the ileum[32].
Glutamine	In rats with an 85% small bowel resection, feeding a 2% glutamine-enriched TPN solution, enhanced intestinal adaptation as assessed by
	mucosal villus height, and mucosal DNA content[33].
	A glutamine-enriched diet enhanced ileal hyperplasia in rats with an 80% small bowel resection[34].
	In rats with a 70% small bowel resection, feeding a 5% glutamine-enriched rats chow diet inhibited intestinal adaptation as assessed by
	duodenal protein content and ileal DNA content[35].
	A 2% glutamine-enriched elemental diet did not alter markers of intestinal adaptation in rats with a massive small bowel resection[36].
	A 4% glutamine-enriched oral diet did not significantly alter intestinal adaptation after intestinal resection in rats[37].

Table 3 Molecules that regulate intestinal adaptation

Molecule	Effect on Intestinal Adaptation
Glucagon-Like	Treatment of rats with a 75% mid small bowel resection with twice daily injections of 0.1ìg per gram of bodyweight for 21 d induced led to
Peptide 2	mucosal hyperplasia in the proximal jejunum but not in the terminal ileum and a significant increase in intestinal absorptive capacity[50].
Interleukin-11	Treatment of rats with a 90% small bowel resectionwith twice daily injections of 125 mg·g-1ªª Il-11 significantly increasedvillus height and crypt
	cell mitotic rates[51].
Keratinocyte Growth	Treatment of rats with a 75% small bowel resection with 3 mg·kg-1·d-1 of KGF enhanced intestinal adaptation as assessed by mucosal
Factor (KGF)	cellularity, and biochemical activity in duodenal, jejunal and ileal segments[52].
Transforming factor-α	Treatment of mice with a 50% small bowel resection with intraperitoneal TGF-α enhanced intestinal adaptation[53].
Growth Hormone	Treatment of rats with a 75% small intestinal resection with 0.1 mg·kg-1·kg-1·2 d-1 d for 28 d enhanced ileal adaptation as assessed by ileal
	mucosal height. Treatment with growth hormone did not alter ileal mucosal DNA content or ileal mucosal IGF-1 content[54].
	Treatment of rats with an 80% jejunoileal resection with synthetic rat GH for up to 14 d did not enhance ileal adaptation[55].
	Treatment of an infant with only 25 cm of jejunum and 2 cm of ileum, with an ileocecal valve, with a 4-week course of 0.5 U/kg of GH
	allowing wean ing from TPN[56].
	Ten patients with short bowel syndrome were treated with daily subcutaneous doses of recombinant human GH (rhGH) of 0.024 mg·kg-1·d-1 or a placebo for 8 wk in a crossover cli nical trial that included a wash-out period of at least 12 wk. Low-dose rhGH doubled serum levels
	of IGF-1 and increased body weight and lean body mass; but there were no significant changes in absorptive capacity of water, energy, or protein[57].
Insulin-like	Treatment of rats with 70% and 80% jejuno-ileal resection with IGF-1 or analogues significantly attenuated malabsorption of fat and
Growth Factor-1	increased weight of stomach and proximal small bowel[58].
	Gastrostomy-fed rats underwent 80% jejuno-ileal resection followed by infusion of 2.4mg·kg-1·d-1 IGF-1 for 7 d. IGF-1 infusion led to a
	modest increase in ileal but not jejunal growth[15].
	Treatment of TPN-fed rats for 7 d with IGF-1 after a 60% jejunoileal resection led to an increase in jejunal mass, enterocyte proliferation and
	migration rates yet had minimal effect on colonic structure[59].
Epidermal Growth	Treatment of rabbits with 2/3 proximal resection with oral EGF (40 µg·kg-1·d-1) for 5 d led to an increase in maltase specific activity and a 3
Factor (EGF)	-4 fold increase in glucose transport and phlorizin binding[60].
	Treatment of rabbits with a 50%-60% small bowel resection with 0.3 µg·kg-1·h-1 for 7 d led to a foufold increase in mucosal dryweight at 3
	wk post-resection[61].
	Treatment of rats with a 75% small bowel resection with 6.25 µg·kg-1·h-1 of EGF increased mucosal thickness at 28 d post-resection[62].
Neurotensin	Treatment of rats with a 75% small bowel resection with 600 µg·kg-1·d-1 led to an increase in the rate of mucosal proliferation[63].

Table 4 The effect of glutamine, growth hormone, and a modified diet on patients with short-bowel syndrome

Authors	Design of Study	Treatment	Number and Type of Patients	Average Length of Remnant Bowel 43	Results
Byrne et al[65].	Uncontrolled study.	GH 0.11 mg·kg-1·d-1, glutamine	47 patients that were	patients with a	At the end of the study 57% of the
	Patients admitted to	0.16 g·kg-1·d-1ªª by the parenteral	chronically dependent	colonic remnant	patients no longer needed TPN, 30%
	hospital and treated for	route with up to 30 g·d-1 by the	on parenteral nutrition	had(50 ± 7)cm[4].	had reduced TPN requirements, and
	21 d.	enteral route, and a diet containing		patients with	6% required approximately the same
		60% of total calories as		no colon had	amount of TPN as they did at the start
		carbohydrate, 20% as fat and 20%		(102 ± 24)cm.	of the study.
		from protein.			One year later 40% of the patients no
					longer needed TPN, 40% had reduced
					TPN requirements, and 20% required
					approximately the same amount of TPN
					as they did at the start of the study
Scolapio[66]	Double-blind, placebo	GH 0.14 mg·kg-1·d-1, glutamine	8 patients that were	71 cm2 patients	Treatment led to a significant increase
Scolapio et al[67].	controlled, randomized	0.63 g·kg-1·d-1 by oral route, and a	dependent on parenteral	had colonic	in bodyweight and lean body mass, a
	crossover study. Patients	diet containing 60% total calories	nutrition for an average	continuity.	significant decrease in percent body fat
	were treated for 21 d as	as carbohydrate, 20% as fat and	of 12.9 years.		and induced peripheral edema.
	out-patients.	20% as protein.			All parameters returned to baseline
					levels within 14 d of stopping treatment.
					Treatment had no significant effect on
					intestinal villus height or crypt depth.
Szkudlarek et al[68].	Double-blind, placebo	GH 0.14 mg·kg-1·d-1, glutamine	8 patients that were	104 cm.4 patients	No significant effect of treat ment on
	controlled, randomized	30 g·d-1 by oral route and	dependent on parenteral	had colonic	absorption of energy, carbohydrate,
	crossover study. Patients	glutamine-enriched parenteral	nutrition for an average	continuity.	nitrogen, wet weight, sodium, potassium,
	were treated for 28 d as	nutrition (17% of nitrogen	of 7 years .		calcium or magnesium. Treatment induced
	out-patients.	as glutamine).			adverse effects.