Short Bowel Syndrome

Content below is from a textbook reference chapter (Sabiston Ch50 - Diverticular Disease & Miscellaneous Problems), not primary literature. See also Crohn Disease, where overly wide historical resections were noted as a cause of this “devastating surgical complication.”

Definition and causes

Results from a total small bowel length that is inadequate to support nutrition. In adults, 75% of cases occur from massive intestinal resection — mesenteric occlusion, midgut volvulus, and traumatic disruption of the superior mesenteric vessels are the most frequent causes. Multiple sequential resections, usually associated with recurrent Crohn disease, account for 25% of adult cases. In neonates, the most common cause is bowel resection secondary to necrotizing enterocolitis.

Clinical hallmarks include diarrhea, fluid and electrolyte deficiency, and malnutrition. Other complications include an increased incidence of gallstones (caused by disruption of the enterohepatic circulation) and nephrolithiasis (from hyperoxaluria). Specific nutrient deficiencies must be prevented, and levels must be monitored closely — including iron, magnesium, zinc, copper, and vitamins.

The likelihood that a patient will be permanently dependent on TPN is thought to be primarily influenced by the length, location, and health of the remaining intestine. In patients with short bowel syndrome, postabsorptive levels of plasma citrulline (a nonprotein amino acid produced by intestinal mucosa) may provide an indicator to differentiate transient from permanent intestinal failure.

The bowel has a remarkable capacity to adapt after small bowel resection — in many cases this process of intestinal adaptation, termed adaptive hyperplasia, effectively prevents severe complications that result from markedly decreased surface area available for absorption/digestion. However, any adaptive mechanism can be overwhelmed, and adaptation is inadequate if too much small bowel is lost. Although there is considerable individual variation, resection of up to 70% of the small bowel can usually be tolerated if the terminal ileum and ileocecal valve are preserved. Length alone, however, is not the only determining factor of complications related to resection — for example, if the distal two thirds of the ileum, including the ileocecal valve, are resected, significant abnormalities of absorption of bile salts and vitamin B12 may occur, resulting in diarrhea and anemia, even though only 25% of the total length of the small bowel has been removed. Proximal bowel resection is tolerated better than distal resection, because the ileum can adapt/increase its absorptive capacity more efficiently than the jejunum.

Treatment

The most important issue is prevention. In patients with Crohn disease, limiting bowel resections to only segments with a particular complication should be performed. During surgery for problems related to intestinal ischemia, the smallest possible resection should be performed, and if necessary, second-look operations should be carried out to allow ischemic bowel to demarcate — thus potentially preventing unnecessary extensive resection of the bowel.

After massive small bowel resection, the treatment course may be divided into early and late phases.

Early phase

Treatment is primarily directed at control of diarrhea, replacement of fluid/electrolytes, and prompt institution of TPN in patients who cannot safely tolerate enteral feedings. Volume losses may exceed 5 L/day, with vigorous monitoring of intake/output and adequate replacement. Diarrhea in this early phase can be caused by a multitude of sources — for example, hypergastrinemia and gastric hypersecretion occur after massive small bowel resection and can significantly contribute to diarrhea. Acid hypersecretion can be managed with H2 receptor antagonists or proton pump blockers (e.g., omeprazole). Diarrhea may also be caused by disruption of the enterohepatic circulation from ileal resection, resulting in excessive amounts of bile salts entering the colon — cholestyramine may be beneficial when diarrhea relates to the cathartic effects of unabsorbed bile salts in the colon. In addition, judicious use of agents that inhibit gut motility (e.g., codeine, diphenoxylate) may be helpful. The long-acting SSA octreotide also appears to reduce diarrhea during the early phase of short bowel syndrome; some studies suggest octreotide may inhibit gut adaptation, though other studies have not confirmed this deleterious effect.

Late phase

As soon as the patient has recovered from the acute phase, enteral nutrition should be started. Elemental (e.g., Vivonex, Flexical) and polymeric (e.g., Isocal, Ensure) diets are the most common types. Controversy exists about the optimal diet for these patients — initially, a high-carbohydrate, high-protein diet is appropriate to maximize digestion; milk products should be avoided; the diet should begin at iso-osmolar concentrations and small amounts. As the gut adapts, the osmolality, volume, and calorie content can be increased. Simple sugars, dipeptides, and tripeptides are rapidly absorbed from the intestinal tract. Reduction in dietary fat has long been considered important for these patients — supplementation of 100 g or more of fat should be carried out, often requiring medium-chain triglycerides (absorbed in the proximal bowel). Fat-soluble vitamins, calcium, magnesium, and zinc supplementation should be provided.

Hormonal therapy: neurotensin, growth hormone, bombesin, and GLP-2 (administered systemically) and glutamine (administered enterally) have demonstrated marked mucosal growth in a variety of experimental studies and prevent gut atrophy associated with TPN; combination therapy appears more efficacious than single-agent administration. RCTs showed teduglutide (a GLP-2 analogue resistant to degradation by dipeptidyl peptidase 4, giving it a longer half-life than natural GLP-2) is well tolerated and led to restoration of intestinal functional/structural integrity through significant intestinotrophic and pro-absorptive effects — the first targeted therapeutic agent to gain approval for pediatric and adult short bowel syndrome with intestinal failure. Growth hormone and IGF-I (hormones not derived from the gut) have also been extensively evaluated: a meta-analysis of RCTs using growth hormone suggests a possible short-term benefit in body weight, lean body mass, and absorptive capacity, but long-term efficacy was not noted. Somatropin (recombinant human growth hormone, anabolic/anticatabolic via direct effect or indirectly through IGF-I) is currently indicated to treat short bowel syndrome in conjunction with nutritional support. The combination of various trophic hormones with glutamine and a modified diet may prove more efficacious in this difficult patient group.

Surgical intervention

The first step is to restore digestive continuity, accomplished by reversal of a proximal stoma, to reduce rates of dehydration. Surgical strategies attempted in chronically-TPN-dependent patients (with limited success): procedures to delay intestinal transit time, methods to increase absorptive area, and small bowel transplantation.

• Methods to delay intestinal transit time: construction of various valves and sphincters; antiperistaltic segments of small intestine have been constructed to slow transit, allowing additional contact time for nutrient/fluid absorption, with moderate successes described. Other procedures (colonic interposition, recirculating loops of small bowel, retrograde electrical pacing) have been tried but were found unsuccessful in humans and were largely abandoned.
• Surgical procedures to increase absorptive area: intestinal tapering and lengthening procedures (e.g., Bianchi procedure, which improves intestinal function by correcting the dilation/ ineffective peristalsis of the remaining intestine and by doubling intestinal length while preserving the mucosal surface area). Serial transverse enteroplasty (STEP) creates staple lines parallel to the mesenteric blood supply on alternating sides to create a channel of intestine that is both longer and smaller in diameter; also increases the surface area of bowel for nutritional absorption. Although beneficial in selected patients, potential complications include necrosis of divided segments due to poor vasculature, stenosis from smaller caliber bowel, and anastomotic leaks.
• Intestinal transplantation: remains the standard of care for patients for whom intestinal rehabilitation attempts have failed and who are at risk of life-threatening TPN complications — including impending liver failure, thrombosis of more than two major access veins, frequent severe line infections, and dehydration. Patient survival after intestinal transplantation has significantly improved with the use of immunosuppressive agents alemtuzumab and tacrolimus, and transplantation at a high-volume center (≥10 grafts/year). 1- and 5-year survival rates for isolated intestinal transplantation are 77% and 58% respectively; combined intestinal-liver transplants have comparable 1- and 5-year survival rates of approximately 66% and 54%. Challenges continue to require better immunosuppression and earlier detection of rejection.

Open items / gaps

• No primary literature yet in the wiki independently appraising teduglutide trials, the growth hormone meta-analysis, or intestinal transplant survival data cited above — currently only the textbook’s narrative summary.