Short Bowel Syndrome

CHAPTER

79 

T

Short Bowel Syndrome Magesh Sundaram 

|

  John Kim

he “normal” length of an adult human’s small intestine has been estimated between 20 and 22 feet, or 609 and 670 cm. Past estimates of normal small intestine length have been between 300 and 800 cm, and this variability is based on measurements from surgical, radiologic, or autopsy measurements.1,2 Short bowel syndrome (SBS) occurs when there is less than 200 cm of small intestine remaining. The minimal length of small intestine necessary to prevent lifelong dependence on parenteral nutrition (PN) is approximately 100 cm if the colon is absent and 60 cm with a completely functional colon present. The etiology of SBS may be congenital or acquired and may be functional or related to surgical resection (Table 79.1).3 In the pediatric population, intestinal atresia (jejunal or ileal) is the congenital etiology, whereas small bowel resection for the diagnoses of necrotizing enterocolitis, gastroschisis, and volvulus are the common acquired etiologies. In adults, SBS is the sequelae of massive or multiple resections of the small intestine. Approximately 15% of all adults who undergo bowel resection exhibit sequelae of SBS, from either massive resection (76%) or multiple resections (24%).4 SBS is seen after multiple intestinal resections performed for the diagnoses of Crohn disease, trauma, malignancy, radiation enteritis, or ischemia and gangrene associated with late-stage small bowel obstruction. Of note, a vascular event of the intestine, such as mesenteric arterial embolism or venous thrombosis, may lead to a single massive resection done as a life-saving maneuver for an apparent intraabdominal catastrophe. Functional SBS is seen without intestinal resection with physiologic loss of function or persistent malabsorption syndromes. Diagnoses that may lead to functional SBS include radiation enteritis, low-grade or indolent malignancies (e.g., pseudomyxoma peritonei), refractory sprue, congenital villous atrophy, and chronic intestinal pseudoobstruction syndrome. SBS is a disabling intestinal condition that reduces the quality and length of life and limits the social integration of the affected individual. The hallmark of SBS is severe nutrient and fluid malabsorption leading to chronic imbalances of micronutrient, fluid, protein, electrolyte, and carbohydrate stores. Quality of life is limited in these patients due to persistent manifestations of SBS via failure to thrive, diarrhea, dehydration, malnutrition, and long-term dependence on alternate means of nutritional support. Frequent medical care episodes for nutritional maintenance, as well as acute management of associated complications, interferes with social integration. Historically SBS patients have been on long-term, if not lifelong, PN. However, newer concepts of SBS management, including intestinal rehabilitation (IR), surgical optimization of absorption, and transplantation, are leading SBS patients to enteral autonomy and an improved quality of life.

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INCIDENCE AND DEMOGRAPHICS OF SHORT BOWEL SYNDROME The true incidence of SBS in the United States has not been accurately identified because there are no reliable national registries or patient databases. In addition, on review of surveys of managing gastroenterologists and nutritionists, the accurate diagnosis of SBS is often not identified in the prescription of long-term home parenteral use. The Oley Registry of home parenteral use in North America in 1992 identified 40,000 patients with the broader category of intestinal failure as the diagnosis, with only approximately 26% of cases attributed to SBS.5 Some patients receiving PN in the Oley Registry carried the diagnosis of radiation enteritis or malignancy, and these patients could be reclassified with SBS due to those diagnoses. In 1995, an estimate of 10,000 to 20,000 patients receiving home PN for SBS was made by Byrne et al.6 It is estimated that the number of SBS patients may be in the range of 2 per million, based on extrapolation of home parenteral use for SBS patients in the United Kingdom.7 A more recent European survey from 1997 identified the incidence of home total parenteral nutrition (TPN) use at close to 3 per million and the prevalence greater than 4 per million.8 It would seem that the prevalence of SBS is lower in regions where access to specialized nutritional care is lacking, and this is likely due to underreporting, lack of recognition of the disease process, and a resultant shorter life expectancy. The prevalence of SBS is noted to be 0.4 per million in Poland, whereas it is noted to be 30 per million in Denmark, and this may be attributed to the development of a leading IR center (IRC) in Denmark that has led to a twofold increase in the number of patients listed as receiving PN or intravenous (IV) fluid support over the past 40 years.9 Further underreporting of SBS incidence in both the United States and Europe can be realized when there is no accounting of patients with SBS who do not require home PN/IV support or who have been weaned off PN/IV support. Historically, characterizing the demographics of patients with SBS is limited without a prospective national registry or database. A survey of 688 patients awaiting intestinal transplants and receiving PN/IV support revealed the diagnosis of chronic intestinal failure and 75% also had SBS identified. The age of these patients was 52.9 ± 1.52 (range, 18.5 to 88.0), with 57% women. The most common etiologies were mesenteric ischemia (27%), Crohn disease (23%), and radiation enteritis (11%).10 Similar findings of a median age of 52.5, a majority of females (52%), and a body mass index (BMI) of 20.7 kg/m2 was identified in a study limited to 268 SBS patients. Mesenteric infarction (43%), radiation enteritis (23%), surgical complications (12%), and Crohn disease (6%) were the common

Short Bowel Syndrome  CHAPTER 79 

ABSTRACT Short bowel syndrome (SBS) occurs when there is less than 200 cm of small intestine remaining. The minimal length of small intestine necessary to prevent lifelong dependence on parenteral nutrition (PN) is approximately 100 cm if the colon is absent and 60 cm with a completely functional colon present. Approximately 15% of all adults who undergo bowel resection exhibit sequelae of SBS, from either massive resection (76%) or multiple resections (24%). Irrespective of etiology, it is a disabling intestinal condition that reduces the quality and length of life and limits the social integration of the affected individual. The hallmark of SBS is severe nutrient and fluid malabsorption leading to chronic imbalances of micronutrient, fluid, protein, electrolyte, and carbohydrate stores. Quality of life is limited in these patients due to persistent manifestations of SBS via failure to thrive, diarrhea, dehydration, malnutrition, and long-term dependence on alternate means of nutritional support. Frequent medical care episodes for nutritional maintenance as well as acute management of associated complications interfere with social integration. Historically, SBS patients have been on long-term, if not lifelong, PN. However, in this chapter, the newer concepts of SBS management including intestinal rehabilitation, surgical optimization of absorption, and transplantation will be discussed. These discoveries are leading SBS patients to enteral autonomy and an improved quality of life.

KEYWORDS Short bowel syndrome, Small intestine, Intestinal rehabilitation, Malabsorption, Malnutrition, Bowel surgery, Bacterial overgrowth

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Short Bowel Syndrome  CHAPTER 79 

TABLE 79.1  Etiologies of Short Bowel Syndrome CONGENITAL Intestinal atresia

ACQUIRED Surgical resection of bowel Recurrent Crohn disease Massive enterectomy secondary to a catastrophic vascular event, such as a mesenteric arterial embolism or venous thrombosis, volvulus, trauma, or tumor resection Gastroschisis Necrotizing enterocolitis Intestinal atresias Extensive aganglionosis Chronic intestinal pseudoobstruction syndrome Refractory sprue Radiation enteritis Congenital villous atrophy Modified from DeLegge M, Alsolaiman MM, Barbour E, Bassas S, Siddiqi MF, Moore NM. Short bowel syndrome: parenteral nutrition versus intestinal transplantation. Where are we today? Dig Dis Sci. 2007;52(4):876–892.

etiologies identified.11 Better recognition of SBS is now being seen with cooperative transplant registry data collection. SBS was identified as the most common primary indication for intestinal transplantation when 61 intestinal transplant programs in 19 countries provided data on 989 transplants in 923 patients.12

PROGNOSTIC FACTORS IN SHORT BOWEL SYNDROME SBS is associated with short- and long-term complications that lead to significant morbidity and mortality. Historically the prime determinant of mortality in SBS patients was nutritional failure, as seen with a case-fatality rate of 37.5% in neonates, among an SBS incidence of 24.5 per 100,000 live births.13 The advent of effective long-term PN and indwelling central venous access in the late 1960s led to good nutritional rehabilitation with low complication rates in SBS patients. In the two decades following, widespread adoption of PN support led to a reduction in SBS mortality from nutritional failure. The current era of SBS management includes pharmacologic medical therapies, multidisciplinary IRCs, and surgical intestinal optimization and transplant procedures. These management principles have led to improvement in both morbidity and mortality rates in SBS patients. Fifty percent to 70% of patients who require PN after the initial diagnosis of SBS can be weaned off PN within 2.5 years of the referral to a specialized center. Up to 70% of pediatric SBS patients can now be discharged from the hospital and are alive 1 year after diagnosis.14 The prognosis of SBS is dependent on several factors, including the remaining length of functional intestine, the active presence of underlying etiologic diseases (Crohn, radiation enteritis, vasculopathy), the presence or functional continuity of the colon, and the ileocecal valve (ICV). Previously, it was felt that the ICV carried a greater

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role in gate-keeping transit times of intestinal loads to the colon, as well as preventing colonic reflux. However, when subsets of SBS patients are matched for length of intestinal resection, the value of the ICV appears to be primarily a marker of greater ileal or colon resection.15 The patient’s age at presentation and the chronicity of enteral dependence are also contributing prognostic factors. Buchman reports the overall survival rate after 6 years of enteral dependence to be 65% in patients with at least 50 cm of intestine, but survival rates are much lower in patients with less than 50 cm of intestine.16 These patients with less residual intestine are more likely to develop PN-related complications, such as liver and kidney failure if not being permanently dependent on PN. The mortality in SBS patients with well-established PN dependence and with adequate residual intestine is less likely to be due to PN-related complications and more likely to be due to complications of their underlying disease, such as Crohn disease, cancer, and heart failure.

NORMAL INTESTINAL PHYSIOLOGY AND PATHOPHYSIOLOGY OF SHORT BOWEL SYNDROME The normal intestinal physiology of an intact digestive system is notable for a progressively decreasing absorptive gradient from proximal to distal. The absorptive surface area of the duodenum and jejunum is greater than that of the ileum. The proximal jejunum contains plicae circulares in greater number and thickness and with longer villi than the ileum. The absorptive surface area is also larger in the proximal intestine because the luminal diameter decreases as the gastrointestinal (GI) tract progresses from duodenum to ileum. Direct proximity to biliary and pancreatic enzymatic activity in the duodenum and jejunum is a major driver of nutrient digestion and absorption, more so than what is seen in the ileum, where bile acid resorption is a more prominent function. The absorption of nutrients, minerals, vitamins, and amino acids is carefully distributed to preferential areas along the GI tract, as described in Chapter 71 (Fig. 79.1).17 The anatomy, length, and reconfiguration of the GI tract that remains after intestinal resection in the setting of SBS directly affect the proximal to distal gradient of digestion and absorption of nutrients and fluids. The small intestine has a large functional reserve capacity, and resection of up to 50% of intestinal length can be well tolerated. However, crossing the threshold of less than 200 cm of residual intestine leads to some of the clinical sequelae of SBS in at least 50% of these patients. The progression to massive intestinal loss leads to the full manifestation of SBS via the pathophysiology of loss of absorptive surface area and an increase in intestinal transit times. The clinical consequences of SBS are a result of the loss of intestinal absorption surface, the loss of sitespecific absorptive areas, the loss of the ICV, and the decrease in intestinal hormone production. After major intestinal resection, larger volumes of undigested nutrients result in hyperosmotic loads entering the distal GI tract sooner, resulting in a response of increased luminal water. The resulting intense diarrhea is one of the major

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SECTION II  Stomach and Small Intestine

Release sites of humoral and neural mediators of nutrient processing

Nutrient absorption sites

Stomach: • Gastrin

Duodenum/proximal jejunum: • Fats • Sugars • Peptides/amino acids • Iron • Folate • Calcium • Water-soluble vitamins

Duodenum: • Cholecystokinin • Secretin • Glucose-dependent insulinotropic polypeptide • Vasoactive intestinal peptide

Jejunum/proximal ileum: • Fats • Sugars • Peptides/amino acids • Lactose • Calcium • Water-soluble vitamins

Jejunum/ileum: • Neurotensin

Distal ileum: • Bile salts • Vitamin B12

Distal ileum and colon: • Peptide YY • Glucagon-like peptide 1 • Glucagon-like peptide 2

Colon: • Amino acids and carbohydrates (via SCFAs)

B

A

FIGURE 79.1  Nutritional absorption (A) and hormonal release sites (B) across the gastrointestinal tract. SCFAs, Short-chain fatty acids. (From Tappenden KA. Pathophysiology of short bowel syndrome: considerations of resected and residual anatomy. J Parenter Enteral Nutr. 2014;38[suppl 1]:14S–22S.)

TABLE 79.2  Anatomic Subtypes of Short Bowel Syndrome Subtype

Resection/Remnant

1. Jejunal-ileal anastomosis

Majority of jejunum resected. 10+ cm of ileum, ICV, colon remain All/most ileum resected. Parts of jejunum, colon may also be resected Some jejunum retained. Ileum, ICV colon removed. End jejunal ostomy

2. Jejunal-colic anastomosis 3. End jejunostomy

Avoidance Permanent PN Dependence

GI Tract Pathophysiology

Usually good but poor if <40 cm jejunum remains

Impaired digestion, increased gastric acid secretion

Diarrhea

Variable but poor if <65 cm jejunum remains

Deficiencies in vitamin B12, bile salts, fat-soluble vitamins. Fat malabsorption Deficiencies in vitamin B12, bile salts, magnesium. Fluid and nutrient malabsorption

Diarrhea, steatorrhea

Variable but poor if <100 cm jejunum remains

Clinical Manifestations

Excessive ostomy output, dehydration

GI, Gastrointestinal; ICV, ileocecal valve; PN, parenteral nutrition.

symptoms of the initial phase of SBS manifestation. The consequence is decreased digestion and absorption of lipids and fat-soluble vitamins, as well as emulsification and processing of cholesterol and complex fats. Intestinal resection and reconstruction of the GI tract in the setting of SBS can be categorized into three anatomic subtypes (Table 79.2). Type I is associated with significant jejunal resection and GI tract reconstruction via a jejunalileal anastomosis. The remnant GI tract includes at least 10 cm of terminal ileum, the ICV, and the entire colon. Type II is associated with resection of most or all of the ileum, frequently the ICV, and possibly part of the colon,

usually the proximal or right colon. The GI tract in type II SBS patients is frequently reconstructed via a jejunocolic anastomosis. Type III SBS occurs with resection of all of the ileum, ICV, and the colon, with variable resection of the jejunum. The GI tract output is via an end jejunostomy, without connection to the rectum and anus. Type I SBS patients have the greatest chance of nutritional recovery over time. Although there is initial loss of the proximal to distal gradient associated with the proximal jejunum, there is greater potential for the development of functional adaptation by the ileum to reduce the severity of nutritional losses long term. The possibility of intestinal

Short Bowel Syndrome  CHAPTER 79 

adaptation is good with type I, and the permanent need for PN is low. In type I SBS, intestinal failure and the need for permanent PN or transplant consideration occur more commonly when only less than 40 cm of jejunum (or <10% of expected intestine for gestational age in infants) remains to form the jejunal-ileal anastomosis. Clinical manifestations may be seen due to changes in intestinal endocrine regulation. Loss of cholecystokinin production in the postresection state leads to increased gastric acid hypersecretion and rapid intestinal transit time of fluids. Alteration of the intestinal pH from increased acid load can lead to reduced pancreatic enzymatic digestive capabilities. Fortunately, the acid hypersecretion postresection state can be corrected in a few weeks to months, with the addition of a proton pump inhibitor or H2-blocker regimen.18 Type I SBS patients tend not to have dehydration issues long term because the intact colon can serve as a water reservoir and absorptive conduit. When the duodenum and at least 40 cm of jejunum are preserved, deficiencies of water-soluble vitamins are less typical because these areas of the proximal intestine can slow down water-soluble vitamin absorption times. Type II patients typically exhibit more severe clinical manifestations of SBS due to the loss of the adaptive capacity of the ileum and the colon. More extensive ileal resections are associated with worse outcomes. When less than 65 cm of jejunum remains and no ileum, the avoidance of permanent PN dependence is poor in these type II SBS patients. Clinical manifestations occuring with ileal resections are due to disruption of the vitamin B12 and enterohepatic bile salt systems. Without the site-specific ileal B12 receptors, long-term maintenance with vitamin B12 supplements is needed. Lacking bile salt reabsorption, steatorrhea from fat malabsorption is a frequent manifestation. The persistence of unabsorbed bile salts in the colon stimulates colonic motility and secretion, further exacerbating the steatorrhea. Chronic deficiencies of the fat-soluble vitamins will lead to the expected clinical presentations—dry skin, night blindness and xerophthalmia (vitamin A), pediatric rickets and adult osteomalacia and osteoporosis (vitamin D), macular degeneration (vitamin E), and spontaneous hemorrhage and poor clotting ability (vitamin K). Type III patients with an end jejunostomy are the most challenging to manage because they have high fluid output losses. Without both the ileum and the colon, they will have the greatest malabsorptive issues as compared with the other patients. End jejunostomy patients no longer have the water reservoir and absorptive potential of the colon but also lose ileal site-specific nutritional deficiencies. When end jejunostomy patients have less than 100 cm of jejunum remaining, there is the added issue of loss of gastric acid and intestinal secretions, resulting in a chronic net-secretory state of high fluid output. The type III patients with less than 100 cm of jejunum typically will need permanent PN/IV support. Water losses become less of a permanent issue with an intact ileum and colon. Permeability to water is less in the ileum than jejunum because the ileum has tighter junctions and a narrower luminal surface area. Therefore less water enters the ileal lumen than the jejunal lumen in response to a hyperosmotic-loaded meal. In adaptation,

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the colon is capable of increasing its fluid absorption capability from approximately 1.8 to 5 L a day, or up to 400% of normal.19 However, patients with a resected colon (type II SBS) or with an end jejunostomy (type III SBS) may have significant water and sodium losses that may lead to acute hypotension and chronic kidney insufficiency states. Hypomagnesemia in particular may lead to muscle fatigue, cardiac dysrhythmia, and neurologic impacts from depression to seizures.

INTESTINAL ADAPTATION Intestinal adaptation is the mechanism of GI tract functional recovery that occurs in the postresection state of SBS patients. This adaptive process begins within 24 hours of significant intestinal resection and continues over a 2-year period. The degree or success of intestinal adaptation depends on anatomic factors, such as the extent and site of intestinal resections, the patient’s health and existent underlying disease processes, the mechanism of nutritional support, and regaining the endocrine regulatory mechanisms of the GI tract. Keller20 has identified three phases of intestinal adaptation: • Acute phase—postresection to 4 weeks. The goal is stabilization of the patient’s sequelae of diarrhea, malabsorption, and dysmotility. • Adaptive phase—1 to 2 years. The goal is achieving maximal intestinal adaptation with a gradual increase of nutritional exposure. • Maintenance phase—long term. Optimizing fluid balance and individualized dietary regimen. Management of acute exacerbations. Successful intestinal adaptation depends on morphologic changes in the residual intestine’s microanatomy. The absorptive capacity may be increased by several hundred percent from increased mucosal surface, as well as increased absorption per surface area. In the postresection state the acute phase is marked by hyperemia of the bowel wall. Increased blood flow to the remnant intestine may be seen for up to 4 weeks after resection.21 Hyperemic changes promote mucosal hyperplasia, with resulting increased number and size of crypts and villi in the ileum. The normal ileum is typically exposed to fewer luminal nutrients than the jejunum. Taking advantage of the ileum’s adaptive capability, therapeutic stimulation via planned and gradual exposure of macronutrients to ileal intestinal mucosa leads to a net increase in the absorptive surface area.22 Intestinal wall lengthening, luminal diameter increase, and wall thickening can occur in the ileum. Such adaptive growth of intestinal length and diameter is most prominent in premature babies with SBS.23 After morphologic changes occur over the initial 2-year period, there is evidence of retention of these features—Joly has reported that there is a 35% increase in crypt depth and a 22% increase in cell numbers and crypts in type II jejunocolic anastomosis patients up to 9.8 years after resection, as compared with healthy controls.24 Functional changes in intestinal enterocytes are further key elements of increasing absorptive capacity. Differentiation of specialized mucosal cells may occur, thereby optimizing electrolyte (sodium, calcium) transport and

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SECTION II  Stomach and Small Intestine

exchange processing.25 Such differentiation occurs at the microvilli level. Functional adaptation occurs in the remnant colon through the process of hyperfermentation of undigested carbohydrates by colonic bacteria.26 Carbohydrate conversion to short-chain fatty acids (SCFAs), which are then absorbed in the colon, has proved to be an energy preservation mechanism.27 Slowing small bowel transit time and thereby lengthening the time of contact between nutrients and the absorptive surface area is a change that improves quality of life. Although diarrhea is a prominent feature of the acute phase, long-term success in fluid, electrolyte, and nutritional balance can be achieved during the adaptive phase with deceleration in intestinal transit time.28 Although calorie maintenance can be achieved with PN, the intestinal structural integrity can only be maintained via enteral stimulation. Lack of enteral nutrition leads to mucosal atrophy, blunting of villi and crypts, changes in brush border integrity, and increased fluid permeability. Intestinal adaptation is highly dependent on the luminal presence of nutrients. Increased complexity of nutrients seen by the remnant intestine promotes greater adaptation, by promotion of pancreaticobiliary secretions, stimulation of neurohormonal endocrine release, and ongoing use of the absorptive surface area. For example, long-chain triglycerides induce intestinal hyperplasia to a greater extent than medium-chain triglycerides.29 Certain nutrients are more valuable in the promotion of intestinal adaptation. Glutamine is the primary energy source for enterocyte growth and metabolism. Studies that have examined the utility of glutamine in intestinal adaptation show modest benefit clinically. Glutamine added as a supplement to PN does reduce the severity of PN-induced intestinal atrophy. In contrast, glutamine added as part of a nutritional dietary regimen does not seem to yield measurable structural intestinal changes, such as villous growth. The lack of glutamine-driven effect may be due to the greater complexity of the luminal nutrients of the existing dietary regimen. The combination of glutamine with growth hormone (GH) is perhaps more valuable clinically. Studies of SBS patients receiving GH plus glutamine show greater long-term fluid and electrolyte maintenance as well as reductions in PN/ IV volume requirements compared with patients receiving GH alone.30 A Cochrane meta-analysis of human trials indicated that GH, with or without glutamine, improves energy absorption and weight gain in SBS patients, but such benefits were lost when GH therapy was discontinued.31

MEDICAL MANAGEMENT The main goals of medical management of SBS are the optimization and maintenance of • nutritional absorption • fluid and electrolyte balance • vitamin and trace element retention • nutritional and weight maintenance In the acute phase after intestinal resection, attention must be paid to the dominant clinical issue of massive diarrhea and attendant fluid and electrolyte loss. The first few postoperative days require IV fluid replacement of losses, preferably using lactated Ringer with glucose

TABLE 79.3  Drug Therapy Recommendations in the Acute Phase of Short Bowel Syndrome Management Drug

Dose per Day

Cholestyramine Famotidine Loperamide Metronidazole Pancreatic enzyme Octreotide Omeprazole Ranitidine

4–16 g 40–80 mg 4–16 mg 800–1200 mg 25,000–40,000 U per meal 50–100 µg 2–3 times 20–40 mg 300–600 mg

solution (dextrose 5% [D5]). A schedule of replacement of water-soluble vitamins and trace elements must be instituted. Gastric acid hypersecretion should be controlled with proton pump inhibitor and H2-blocker therapy for the first 6 months. Occasionally, the somatostatin analogue octreotide is useful to reduce the intraluminal fluid load, especially in the type III patients with end jejunostomies. Diarrhea may be controlled with the judicious use of intestinal motility inhibition agents, such as loperamide. Cholestyramine is useful in promoting bile salt retention and should be used to reduce cholerheic diarrhea. Sepsis control and correction of postoperative infection is critical to preventing ileus and early intestinal atrophy. Metronidazole is useful in the prevention of small bowel bacterial overgrowth (SBBO). A regular schedule of maintenance drug therapy is recommended in the acute phase for SBS patients (Table 79.3). Enteral nutrition should begin by postoperative day 4 to 5, via a low continuous infusion via nasal/percutaneous feeding tube, or by oral intake. The institution of early enteral feeding may be tempered by surgical concerns about ongoing ischemic changes in the massive vascular accident patient or for anastomotic integrity, peritoneal infection, or septic shock. Initial assessment of the adequacy of early enteral nutrition may be difficult because initial use of the remnant GI tract will lead to apparent worsening of diarrhea. The nutritional load will typically exceed immediate remnant absorptive capacity. A goal of 30 to 40 kcal/kg per day should be sought, but, given potential malabsorption rates of 30%, up to 45 to 60 kcal/kg per day may be the input level of enteral nutrition. Enteral nutrition over the first 3 to 4 weeks after resection should progress with a structured program of increasing nutrient loads, first with isotonic salt-glucose solutions. Similarly, the nutritional program should introduce elemental level amino acids early on, including glutamine. Medium-chain triglycerides are preferred in the acute phase, for patients with a preserved colon, but not in type II or III SBS patients. For type II or III patients, a dietary balance of 40% to 50% carbohydrates and 30% to 40% lipids is recommended (Table 79.4).32 In the beginning of the adaptive phase, past the 4-week point, dietary expansion begins with long-chain triglycerides, free fatty acids, and carbohydrates such as maltose, saccharose, and pectin. Proteins should comprise approximately 20% of the diet. In patients with an intact colon, soluble dietary fibers can be degraded by colonic bacteria to yield SCFAs and provide a supplementary

Short Bowel Syndrome  CHAPTER 79 

TABLE 79.4  Dietary Recommendations in Maintenance Phase of Recovery Nutrient

Small Bowel Ostomy

Colonic Continuity

Carbohydrates

50% of total energy; complex carbohydrates including soluble fiber, limit simple sugars 20%–30% of total energy 40% of total energy

50%–60% of total energy; complex carbohydrates, including soluble fiber

Proteins Fats Fluids

Vitamins

Minerals

Meals

ORS important; minimize fluids with meals, sipping of fluids between meals Daily multiple vitamin with minerals; monthly vitamin B12; possibly vitamins A, D, and E supplements Generous use of sodium chloride on food; calcium 1000–1500 mg daily; possibly iron, magnesium, and zinc supplements 4–6 small meals

20%–30% of total energy 20%–30% of total energy Minimize fluids with meals, sipping of fluids between meals Daily multiple vitamin with minerals; possibly vitamin B12; possibly vitamins A, D, and E supplements 400–600 mg calcium with meals; possibly iron, magnesium, and zinc supplements; reduced oxalate 3 small meals plus 2–3 snacks

ORS, Oral rehydration solution. Modified from Wall E. An overview of short bowel syndrome management: adherence, adaptation and practical recommendations. J Acad Nutr Diet. 2013;113:1200–1208.

energy supply of up to 500 to 1000 kcal/day.33 These patients benefit from a carbohydrate-rich diet but should avoid lipids. Soluble fibers also promote better formed stool production as opposed to insoluble fibers, which can promote diarrhea. Steadfast attention and maintenance of elemental levels, particularly magnesium and calcium, is also required at the early adaptive stage. Calcium supplementation should be at the 800- to 1200-mg/daily oral. Oxalates in the diet should be avoided to prevent the development of oxalate nephrolithiasis. Development of metabolic acidosis may be treated with addition of bicarbonate during the first few months of the adaptation phase. Oral magnesium supplementation may not be possible, due to the laxative effect of enteral magnesium. A generic formula of PN may be started in the early postoperative period, with tailoring to an individual PN formula after the first week, dependent on review of electrolyte levels. In the first two phases of SBS recovery, the desired PN balance consists of 3 to 5 g/kg per day carbohydrates, 1.5 g/kg per day protein, and 1 g/kg per day lipids. Progression to the maintenance phase is with an emphasis of reduction/termination of PN. If intestinal adaptation is mature and the balance between delivery

925

and loss of nutrients is equilibrated, these patients may regain substantial quality of life. The widespread adoption of PN led to significant reduction in morbidity and mortality in SBS patients in the 1970s. One-year survival of SBS adult patients on PN was recognized to be 91%, but leveling off at 86% at 5 years.34 The long-term utility of PN is counterbalanced by PN-related complications, such as indwelling catheter–associated septic and venous thrombotic events, as well as the development of PN-associated liver disease (PNALD). Fifteen percent of PN-dependent patients will develop end-stage liver disease, which carries a 100% mortality rate within 2 years of diagnosis.35 Oral nutrition in the stable SBS patient should consist of many small meals, with an emphasis on a high-fat diet and moderate fluid intake with meals. Accounting for chronic malabsorption rate reduction from the acute 30% potential, the maintenance diet should still be balanced to achieve target absorption rate of 30 to 40 kcal/kg per day. The transition to the high-fat diet of the maintenance phase may yield recurrence of steatorrhea symptoms for which the patient should be prospectively counseled and managed appropriately. Novel drug therapy for SBS includes the use of teduglutide for PN-dependent patients. Teduglutide is the recombinant human analogue of glucagon-like peptide 2 (GLP-2). Both GLP-1 and GLP-2 are intestine-trophic hormones released by the endocrine L cells in the ileum and colon. Upregulation of GLP-1 and GLP-2 synthesis is seen after ileal resection if there is remaining colon in a jejunocolic configuration. These GLP hormones promote villous height and crypt cell mass increase. In a randomized placebo-controlled phase III trial, the use of 0.05 mg/kg/day SQ of teduglutide led to a significant decrease in weekly PN volume requirements of 32% versus 21% in the placebo group (P < .001) by 24 weeks.36 Teduglutide-associated PN volume reduction also led to improved quality-of-life scores among SBS patients.37 The increased crypt cell mass growth caused by teduglutide raises the concern for promotion of neoplastic growth, and therefore a prospective colonoscopy prior to teduglutide therapy is recommended to exclude active intestinal malignancy.

MULTIDISCIPLINARY INTESTINAL REHABILITATION Although the population of SBS patients may be small, they have complex pathophysiology and require an intense focus of care to lead successful lives without morbidity and mortality. A newer paradigm in the care of SBS patients is multidisciplinary IR at a specialized intestinal care center. These IRCs offer SBS patients a comprehensive management approach that recognizes the nutritional management challenges and short- and long-term complications and transitions patients from medical/pharmacologic management to surgical interventions of intestinal reconstruction or transplant. Clinical pathways are triggered with an SBS patient from the initial postsurgical phase, the IR phase, with monitoring for complications (Fig. 79.2).38 An IR program’s wellestablished clinical pathways are tailored to the individual

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SECTION II  Stomach and Small Intestine

• Postsurgery stabilization with parenteral support

FIGURE 79.2  Clinical pathways of short bowel syndrome patients at intestinal rehabilitation center (IRC). (From Matarese LE, Jeppesen PB, O’Keefe SJ. Short bowel syndrome in adults: the need for an interdisciplinary approach and coordinated care. J Parenter Enteral Nutr. 2014;38[suppl 1]:60S–64S.)

Initial postsurgery

Intestinal rehabilitation program

Complications

Monitoring

• Appropriate specialist involvement

SBS patient with an emphasis on patient education. In addition to the fluid, nutritional, and medical management in the initial postsurgical phase of SBS, educational counseling is oriented toward the patient’s understanding of the major lifestyle changes ahead, as well as broadening familiarity of the program’s services and capabilities of support. Understanding the intestinal remnant and configuration, as well as the patient’s underlying health, leads to the formulation of a detailed nutritional assessment of the degree of short- and long-term nutritional deficits. Specialized IRCs typically have a gastroenterology program director with nutritional, medical, pharmacy, surgical, interventional radiology, and social work team members (Fig. 79.3). 38 Pathways are developed in a coordinated fashion to seamlessly hand off the SBS patient from one major transition point to the next—for example, specialist referral for an acute complication, or surgical referral for transplantation in the setting of intestinal failure (Table 79.5).38 One such important transition point is the first discharge from the hospital to a home care environment. A specialized IR program will have established protocols of communication between the patient, the nutrition specialist (PN/enteral nutrition/fluid support), the pharmacist (for relevant medications), and the social worker. Patient recognition of symptom exacerbations (e.g., dehydration, diarrhea, cramping) is prospectively co-managed to reduce severity or minimize hospital readmissions. Studies indicate that IRCs are capable of delivering improved outcomes in SBS patients. Nehme39 compared 211 patients whose PN was managed by a dedicated nutritional support team (NST) against 164 patients whose PN was managed by a variety of individual physician providers, over a 2-year period. The NST group had a catheter complication rate of 3.7% versus 33.5% in the non-NST group. Catheter sepsis rates were 1.3% in the NST group and 26.2% in the non-NST group.39 NST management led to a 50% decrease in complication rates when compared with the group managed by individual

• Evaluation and strategy for individualized care • Coordination of care between IRC and local care

• Nutrition assessments • Laboratory tests • Periodic review at IRC

physicians (P < .001).40 Such coordinated care of the SBS patient on PN may yield cost savings of $4.20 for every $1.00 assigned to the use of a NST.40

COMPLICATIONS OF SHORT BOWEL SYNDROME In addition to the specific nutritional, metabolic, and fluid deficiencies associated with SBS, there are several notable and specific complications that arise in the management of these patients.

SMALL BOWEL BACTERIAL OVERGROWTH SBBO is a common complication associated with SBS. The inherent bacterial load in the GI tract is primarily in the oropharyngeal and colorectal domains. In the normal GI tract, bacterial contamination in the small intestine is limited by the bactericidal action of gastric acid, enzymatic digestion, antegrade peristalsis, and the ICV. However, the alterations of the GI tract’s structure and function in SBS can lead to overabundance of bacterial contamination in the remnant small intestine. The pathophysiologic changes that lead to bacterial overgrowth include villous atrophy, loss of the gut-associated lymphoid tissue, reflux of colon bacteria in the absence of the ICV, and rapid intestinal transit time. SBBO is recognized as the symptomatic presence of more than 105 colony-forming units (CFU)/mL in the intestine. Symptoms include dyspepsia, abdominal cramping, bloating, and diarrhea acutely. Persistence of SBBO may lead to chronic nutritional malabsorption and weight loss. The definitive diagnosis of SBBO is made with endoscopic capture and culture of small intestinal fluid, with identification of 105 + CFU/mL of bacteria. Hydrogen breath testing is a simple, noninvasive alternative means of diagnosis wherein the hydrogen produced by bacterial metabolism of intestinal carbohydrates can be measured from the patient’s breath. Colonic bacterial fermentation

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927

Oversight of management strategy: Gastroenterologist Central coordinator: Varies depending on IRC (e.g., clinical nurse specialist) Nutrition and fluid management: Dietitian Pharmacist

Pharmacologic management: Gastroenterologist

Catheter placement: Interventional radiologist Surgeon Nurse

Stoma care: Nurse

Complication specialists: Infectious disease Endocrinologist Cardiologist Nephrologist Orthopedist Others as needed

Surgery: Surgeon Transplant team

Supportive care: Psychiatrist Psychologist Social worker

Home support: Social worker Family members

Home PS infusions: Nurse IRC team

Monitoring: Home doctor office Outpatient clinic Laboratory

Local healthcare

FIGURE 79.3  The framework of intestinal rehabilitation. IRC, Intestinal rehabilitation center. (Modified from Matarese LE, Jeppesen P, O’Keefe SJ. Short bowel syndrome in adults: the need for an interdisciplinary approach and coordinated care. J Parenter Enteral Nutr. 2014;38[Suppl 1]:60S–64S.)

of simple carbohydrates may not only lead to increased hydrogen load orally but eventually metabolic acidosis with a high anion gap. Treatment of an acute SBBO state depends on the precipitating factors, bacterial species involved, and the severity of symptoms. Most commonly, empiric treatment for SBBO is with the regular use of broad-spectrum oral antibiotics or the regular regimented use of metronidazole. In addition, recognition of contributory anatomic abnormalities such as fistulas, strictures, and diverticula is valuable; surgical correction of these issues may provide immediate relief from the SBBO load. Altering the dietary composition away from carbohydrate loads will ameliorate the etiology of colonic bacterial fermentation. Antimotility agents should not be used to control diarrhea when the diagnosis of SBBO is made. Probiotic (Lactobacillus and Bifidobacterium) therapy may be effective in reducing the use of antibiotics and controlling symptoms of bacterial overgrowth. Probiotic bacteria demonstrate a mucosal barrier–enhancing capability with their adherence to intestinal villi, therein displacing

pathogenic bacteria into the intestinal lumen for discard. Probiotics offer resistance to pathogenic bacterial colonization by direct competition to attachment sites and for nutrients. GI tract intestinal immune functions, such as the secretion of antibacterial peptides (defensins), are enhanced by probiotics.41

CATHETER-RELATED INFECTIONS The long-term use of central venous catheters (CVCs) is a central feature of the management of SBS patients. CVCs are needed to maintain hydration and nutritional status, as well as antibiotic and pharmacologic agent delivery. A common morbidity associated with CVCs is catheter-related infection (CRI) with an incidence of 3% to 60% over the life span of the CVC.42 At least one hospitalization a year for SBS patients is from CRIs. CVC sepsis is a dominant cause of mortality in SBS patients, with up to one-third of SBS patient deaths from this issue, with a 50% 5-year mortality rate.14 CVC infection in the SBS patient population is commonly from coagulase-negative Staphylococcus spp., S. aureus, or gram-negative bacilli.

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TABLE 79.5  Components of an Interdisciplinary Intestinal Rehabilitation Program SERVICE COORDINATED PROCESSES Medical Evaluation

Catheters

Pharmacologic Complications Transplantation option

Standardized diagnostics for physical and biochemical assessments Protocols with interventional radiologists, surgeons, and nurse team Review options and protocols with nutrition team Protocols for referral to appropriate specialists Referral to transplant team

Nutrition Diet modifications support EN management

PN management Procedures for delivery of nutrient solutions to the home setting PN weaning

Protocols for optimized fluid, macronutrients, and micronutrients Protocols for initiation, transitioning, and discontinuation of EN Protocols for fluid, macronutrients, and micronutrients support —

SURGICAL MANAGEMENT

Psychosocial Educational

SBS patients who are on PN over 1 year and in 15% to 40% of adults on long-term home PN use.34 Steatosis occurs with the hepatic accumulation of lipids or glycogen from excess caloric intake. In PN use, parenteral carbohydrate calories may be converted to triglyceride, or excess lipid infusion. Other factors that promote steatosis include deficiencies in essential fatty acids, choline, and taurine.44 Lack of enteral intake in both infants and adults leads to decreased levels of GI hormones. Reduced GI hormone levels result in intestinal stasis and loss of gallbladder contractility. Transient subclinical episodes of SBBO and bacterial translocation lead to cholestasis and stone formation in the liver and gallbladder, with associated increased levels of lithocholic acid. A subclinical septic state in the GI tract promotes IFALD because of the combination of reduction of bile flow, increased lithocholic bile salt production, and decreased enterohepatic bile salt cycling. The contemporary prevention of liver disease in SBS patients is primarily prophylactic or monitoring and intervention to prevent progression. Routine enteral feeding in the maintenance phase for SBS patients should consist of at least 20% to 30% of the total daily caloric intake, thereby promoting GI hormonal release and normal function of the enterohepatic bile salt cycle. Acute and subclinical episodes of SBBO should be prevented with maintenance antibiotic therapy. PN mixtures should be carefully balanced in terms of carbohydrate and lipid loads in addition to maintenance of taurine and cysteine.

Standardized assessments Referrals for emotional support Patient and family material focused on diet, behavior, and self-monitoring

EN, Enteral nutrition; PN, parenteral nutrition. Modified from Matarese LE, Jeppesen PB, O’Keefe SJ. Short bowel syndrome in adults: the need for an interdisciplinary approach and coordinated care. J Parenter Enteral Nutr. 2014;38(suppl 1):60S–64S.

An integrated team approach to the management of CVCs is needed with SBS patients. A popular means of prevention and treatment of CRIs with these patients is the use of antibiotic or ethanol locks of the catheters. Mouw et al. describe the daily use of a 70% ethanol lock method that reduced the rate of CRIs from 11.15 per 1000 catheter-days to 2.06 per 1000 catheter-days.43

LIVER DISEASE Liver disease may result from either long-term PN use (PNALD) or from progressive intestinal failure (intestinal failure–associated liver disease [IFALD]). SBS patients may progress along a spectrum of liver disease from cholestasis to steatosis (fatty liver) and then fibrosis/cirrhosis and end-stage liver failure. The cholestatic changes are more prominent in long-term pediatric SBS patients, whereas steatosis is more prominent in adult SBS patients. Factors found to promote fibrosis and cirrhosis leading to end-stage liver disease include use of PN over 1 year, central line infections, cholecystectomy, and intestinal length less than 60 cm. Liver disease is seen in up to 40% to 60% of pediatric

SURGICAL APPROACH TO OPTIMIZATION OF SMALL BOWEL AT INITIAL SURGERY When faced with an initial operation that may require a massive intestinal resection, primary prevention of SBS should be a high priority. Early surgical intervention is paramount in avoiding extensive bowel resection in cases of intestinal ischemia, mesenteric emboli or thrombi, or complete bowel obstruction.45 The goal of resection should be to preserve as much bowel length possible, including the ICV. This difficult intraoperative decision is challenging.46 After final resection, accurate documentation of the length of bowel remaining with or without ICV is important. If a stoma is required, consideration to maturing a stoma next to a mucus fistula may aid in restoring intestinal continuity while avoiding a full laparotomy and an extensive lysis of adhesions. Specific disease processes such as Crohn should prompt a conservative bowelpreserving approach focused on the judicious use of stricturoplasties and minimal bowel resection. Even if SBS is likely after the index case, adjunctive procedures should not be performed at the time of initial surgery. In almost 75% of patients with SBS, intestinal adaptation is sufficient enough to sustain growth and long-term survival and precludes the need for surgical therapy.47

SURGICAL APPROACH TO OPTIMIZATION OF THE REMNANT SMALL BOWEL AT REOPERATION Operation for SBS is a complicated surgical challenge. With enteral autonomy as a goal, each surgical option must be carefully weighed and individualized. Often

Short Bowel Syndrome  CHAPTER 79 

promotility agents (i.e., metoclopramide, cisapride, or erythromycin base) are used to aid in propulsion to improve tolerance.48 In cases with persistent vomiting refractory to antiemetic medication, a jejunal tube can also be used to gain access for distal feeds. Bowel functions are documented and carefully monitored for infectious etiologies (i.e., Clostridium difficile, rotavirus) in the advent of increased stool output. Stool studies are sent, and pathogens are treated with antibiotics if appropriate. Once ruled out, antidiarrheal agents (i.e., loperamide) can be added to slow bowel transit.49 PN is weaned as the enteral tolerance is optimized. Ultimately, patients who fail to achieve PN independence and are burdened with these associated complications are offered autologous intestinal reconstruction surgery (AIRS) or transplantation. In determining which operation to perform, a small bowel follow-through is essential in the preoperative planning process.50,51 Additional questions include whether a stricture will require a stricturoplasty or resection, or if any isolated nonfunctional dilated loops need to be tapered. If hepatic synthetic function is concerning for failure, a liver biopsy is helpful in determining whether a patient has end-stage liver disease, in which case a multivisceral (both small bowel and liver) transplantation should be considered.52 If not performed preoperatively, a liver biopsy should be obtained at the time of surgery. If the results show cholestasis as a consequence of PN, then a prophylactic cholecystectomy may be considered at the time of surgery.53

AUTOGENOUS INTESTINAL RECONSTRUCTION SURGERY The concepts for surgical procedures for SBS revolve around resolving the major functional problems associated with adapted small bowel, namely disordered motility and stasis that leads to bacterial overgrowth.51 Therefore the primary objective for AIRS is to improve intestinal function, optimize bowel motility, and increase the mucosal absorptive surface area.

PROCEDURES TO IMPROVE INTESTINAL FUNCTION Stricturoplasty, Lysis of Adhesions, and Segmental Resection At reoperation, the surgeon must recognize the need to maximize the remnant bowel. In patients with a history of Crohn disease, necrotizing enterocolitis, or multiple abdominal surgeries, the risk of mechanical obstruction secondary to stenosis from inflammation or ischemia or dense adhesions or anastomotic stricture, respectively, is to be anticipated. Adding to this complexity is that dilated proximal bowel due to distal mechanical obstruction is difficult to distinguish from dilated bowel from SBS adaptation. All sources of mechanical obstructions must be sought and corrected to improve intestinal function. All pathologic adhesions are lysed and stricturoplasty is performed over resection if the affected segment of bowel length is short.44 If resection is required, then resection should be kept as short in length as possible with consideration to perform multiple end-to-end anastomoses over large segmental resections with blind loops to optimize the remainder of the remnant bowel.

929

Stoma Takedown and Reestablishing Intestinal Continuity In patients with abdominal catastrophes, stomas are often required in the initial management of patients who subsequently develop SBS. Stoma takedown and reestablishing intestinal continuity offers clear advantages to improving bowel function. In particular, the colon reabsorbs water and prolongs transit time, particularly if the ICV is intact. In addition, the colon regains the major absorptive function of deriving 5% to 10% of daily caloric energy from SCFAs.54 Restoring colonic continuity is functionally equivalent to adding another foot of small bowel.55 If possible, early stoma closure is recommended to enhance adaptation and help in weaning from PN.56 Finally, stoma reversal may offer an improved quality of life for the patient. Although the benefits are evident, the uncertain response of the colon to intestinal continuity should prompt careful patient selection. Unabsorbed bile acids can cause irritation of the colon, resulting in a debilitating secretory diarrhea. In patient with severe malabsorption, diarrhea can develop into perineal complications. In addition, because the bile acids prevent the excretion of oxalate in the stool, the oxalate is absorbed in the colon and the patients become at risk for developing calcium oxalate nephrolithiasis. Therefore the decision for stoma reversal and intestinal continuity should be carefully considered and made on an individual basis. At least 3 feet of small intestine is required to prevent diarrhea and perineal complications.54 The length and location of intestinal remnant, the presence of the ICV, and the patient’s overall condition must all be considered and weighed. Procedures to Prolong Transit or Improve Motility Procedures to slow intestinal transit are applicable to only a small subset of patients with SBS. There is very limited clinical experience, hence the following procedures should be cautiously applied to patients who have near-adequate remnant length and demonstrate rapid transit. Because these procedures have historically been performed during the adaptive phase after massive surgery or at the time when additional bowel is being recruited into the intestinal tract, the efficacy is difficult to track.55 Thompson et al. recommend that these procedures be considered after the patient has had maximum SBS adaptation of bowel.55 Reversal of Intestinal Segment Conceptually, creating a distal antiperistaltic segment generates retrograde peristalsis and disrupts coordinated antegrade propulsion of the proximal intestine. Furthermore, the disruption of the intrinsic nerve plexus slows the myoelectrical activity in the distal remnant, thereby prolonging transition time and improving absorption. The largest case series to date of 38 SBS patients treated with a distally placed reverse segment of 10 to 12 cm concluded that this procedure was a safe alternative to small bowel transplantation in patients with permanent PN dependency, with a minimum small bowel length of 25 cm and without chronic liver failure.57 The literature suggests clinical improvement in slowed intestinal transit and increased absorption in 70% to 80% of patients, although the methods of assessment and follow-up are variable. The length of reversed small intestinal segment

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SECTION II  Stomach and Small Intestine

ranges from 5 to 15 cm. The challenge has been to determine how long the reversed segment should be because long segments could potentiate an interstitial obstruction. The optimal length appears to be approximately 10 cm in adults and 3 cm in children. Children are generally less favorable candidates.58 Colonic Interposition The colonic segment can be positioned in either the isoperistaltic or antiperistaltic orientation to slow transit time. Colonic interposition into small bowel relies on the premise that colonic peristaltic contractions are lower in frequency than the adjoining small bowel. Therefore proximally placed isoperistaltic interposition serves to slow down the rate of nutrient delivery to the distal small bowel. Alternatively, antiperistaltic interpositions are placed distally and function in a similar fashion as the reversed small bowel intestinal segment. The colon also adds the benefit of reabsorption of water, electrolytes, and nutrients, in addition to delaying transit and having an increased effect on absorption. The length of the colonic segment used does not appear to be as critical as in reversed intestinal segments and ranges from 8 to 24 cm in the literature. There also appears to be fewer obstructive complications with isoperistaltic interposition. Complications include colonic dilation and enterocolitis within the transposed segment.59 Intestinal Tapering and Plication Tapering or plication of functionally dysmotile segments have shown to reduce the diameter of the bowel, thereby improving peristalsis and decreasing the bacterial overgrowth. In tapering enteroplasty, the dilated segment of the antimesenteric border is tapered to match the diameter of the intestinal loop. An appropriate-size chest tube can be used as a guide in resection of the excess bowel along the edge of the tube using a stapler or freehand then sutured.46 Unfortunately optimization of the bowel caliber comes at the expense of losing significant absorptive surface. Therefore ideal candidates are those who have stasis and malabsorption in dilated bowel yet have adequate intestinal length. The main advantage of this procedure is that the arterial supply from the mesenteric border is left unaffected. As a result, tapering enteroplasty should also be considered when vascular anatomy of the dilated bowel is not amenable for division for a lengthening procedure (Figs. 79.4 and 79.5).59 Intestinal plication is also designed to improve motility by decreasing the diameter of the dilated lumen, but, by folding the redundant antimesenteric wall into the lumen and imbricated along the serosal edge, no bowel is resected and therefore no mucosal absorptive surface area is lost. In addition, this procedure avoids the concerns of a long anastomotic suture line leak.60 Complications reported include development of bowel obstruction from inverted bowel and suture line breakdown, resulting in redilatation and dysmotility.61 Procedures to Increase Absorption The longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP) have gained widespread acceptance as primary AIRS procedures

FIGURE 79.4  Intestinal tapering and imbrication. (From Thompson J, Sudan D. Intestinal lengthening for short bowel syndrome. Adv Surg. 2008;42:49–61.)

among surgeons. King et al. published a systematic literature review of the LILT and STEP procedures and reported overall survival of 89%, citing no significant difference between the two procedures. Interestingly, LILT has been found to have higher rate of weaned patients, 55% versus 48%, but has been associated with a higher rate of patients receiving transplantations, at 10% versus 6%.62

LONGITUDINAL INTESTINAL LENGTHENING AND TAILORING In 1980 Bianchi reported the LILT procedure in seven pigs and ushered in a new era in SBS management. His technique doubled the length of a loop of small intestine while concurrently reducing the lumen diameter.63 This novel approach combined the benefits of lengthening, as well as intestinal tapering, which delayed transit time without compromise of mucosal surface loss needed for absorption. In 1981 the first clinical application was reported by Boeckman et al., when LILT was used successfully on 50 cm of dilated bowel in a 4-year-old male with gastroschisis and intrauterine bowel necrosis.64 Within 10 weeks, the patient was weaned off TPN and was able to obtain enteral autonomy.65 LILT was designed on the premise that a bifurcated blood supply exists within the mesentery. This anatomy allows for the two layers of mesentery containing the blood vessels to be separated bluntly on the mesenteric side and bowel divided longitudinally along each parallel lumen. The bowel can be divided using staplers or opened

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931

Duodenal transection

Colon

Stimulating electrodes

FIGURE 79.5  Creation of intestinal valves, retrograde intestinal pacing, and loop recirculation. (From Thompson JS, Rikkers LF. Surgical alternatives for the short bowel syndrome. Am J Gastroenterol. 1987;82:97–106.)

and hemiloops created using suture closure. The end result is two isopropulsive “neo” small bowel lumina, each with its individual blood supply. These two fully vascularized small bowel segments are anastomosed isoperistaltically in a gentle S loop, effectively tapering and doubling the length of the original segment (Fig. 79.6).62 Anatomic criteria for patient selection include (1) intestinal diameter greater than 3 cm, (2) length of residual small bowel greater than 40 cm, and (3) length of dilated bowel greater than 20 cm.66 However, regardless of the length, SBS patients with substantial bowel adaptive dilatation secondary to intestinal failure or with life-threatening complications of TPN mentioned previously should receive consideration for LILT.67 The surgeon must also be cognizant that anatomic variations, such as predominant blood supply to one side of the intestinal wall, exist that will limit potential success of the procedure.68 Furthermore, careful consideration is warranted in patients whose mesentery is thickened and scarred due to inflammation or adhesions. For bowel mesentery that is shortened or when the only short gut remaining is a dilated duodenum, the Iowa procedure might be an alternative to the LILT. The Iowa two-step elongation procedure was developed by Kimura et al. and reported in 1993. The initial surgery consists of deseromyotomizing the antimesenteric surface of the dilated segment of bowel to a host organ, such as deperitonealized abdominal wall (Iowa model I),69 decapsulized liver (Iowa model II),70 and adjacent bowel with incised serosa (Iowa model III).71 The concept is to allow vessel collaterals to coapt onto the attached segment of bowel where the two raw and exposed surfaces are reapproximated. After

collaterals have developed, then the second stage consists of a longitudinal split of the parasitized antimesenteric bowel with its own developed blood supply and the mesenteric bowel with the native blood supply. Then an end-to-end anastomosis is created to reestablish intestinal continuity, having created more bowel length.68 The major disadvantage is that multiple laparotomies are required and weeks are needed for the process of coaptation to develop. For these reasons, the Iowa procedure has not had widespread acceptance as a primary means for bowel lengthening but has a place in specific patients when the mesentery is not favorable (Fig. 79.7).59 Bianchi’s review of the worldwide published series of 150 patients for LILT reveals a survival percentage ranging from 30% to 100% and reports that the ability to wean from TPN also varies from 28% to 100%. 64 Multiple complications associated with LILT are anastomotic stenosis, interloop abscess and fistula formation, staple line leakage, and hemiloop necrosis resulting from vascular compromise.65,72 Recurrent dilatation of the lengthened bowel is a common problem that may require additional tapering. Disadvantages to the LILT are that it is a technically challenging procedure that cannot be repeated on the same intestinal segment. In patients unable to wean from PN after LILT, a small bowel transplant (SBTx) was used as a rescue procedure.52

SERIAL TRANSVERSE ENTEROPLASTY In 2003 Kim et al. published a description of the STEP technique in six pigs.73 He then followed up this animal study with a first human case report later that year after

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SECTION II  Stomach and Small Intestine

A

B

B

C

D

A

B A

E FIGURE 79.6  Bianchi procedure. (From Bianchi A. Intestinal loop lengthening—a technique for increasing small intestinal length. J Pediatr Surg. 1980;15:145–151).

performing a successful STEP procedure on a 2-year-old male born with gastroschisis and a complication of dilated surgically lengthened bowel after a Bianchi LILT. The operation successfully increased 83 cm of dilated and previously lengthened bowel to 147 cm.74 The STEP relies on the anatomic premise that the small bowel blood supply from the mesentery runs perpendicular

to the long axis of the small bowel. Therefore placing alternating and opposite transverse staple fires parallel to the mesentery along the length of the dilated bowel results in a zig zag–shaped elongated bowel with minimal vascular compromise. Several technical considerations are to properly orient the small bowel by marking the antimesenteric border so as to prevent twisting and performing

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A

B

C

D

FIGURE 79.7  Iowa procedure. (From Kimura K, Soper RT. A new bowel elongation technique for the short-bowel syndrome using the isolated bowel segment Iowa models. J Pediatr Surg. 1993;28:792–794.)

partial division of the bowel so as not to cause obstruction. The distance between the staple lines is typically 1.5 times the diameter of the remaining lumen. An average of 10 to 20 staple lines are used, reducing the average dilated diameter of 5 to 6 cm to 2 cm and increasing the ultimate length to 1.5- to 2-fold. The length gained will depend on the original length and width of the bowel and number of staple fires. The crotch or apex of the staple line can be reinforced with suture (Fig. 79.8).75

The advantage with the STEP is that it is a simpler bowel lengthening procedure, easily reproducible with minimal manipulation to the mesentery, and no associated bowel anastomosis required. The STEP procedure has been ideal for asymmetrical bowel dilatation and segments of dilated bowel with complicated intricacies such as duodenum with associated pancreas and biliary system, as well as the jejunum and its association near the ligament of Treitz. The significant benefit of the STEP is that it

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SECTION II  Stomach and Small Intestine

3-year-old female with 22 cm of small bowel remaining, resulting from a midgut volvulus. SILT was able to lengthen 11 cm of her dilated 22 cm of small bowel an additional 20 cm, with the total bowel length of 31 cm. The patient was able to wean off TPN with improvement in liver functions but still remained on gastrostomy tube feeds.81 Alberti et al. also reported on the successful application of SILT on a 10-month-old who, at 1-year follow-up, was on the 15 to 25 percentile on 82% oral calories and 18% TPN.82 Long-term data should follow as more successful applications are reported (Fig. 79.10).

TRANSPLANTATION

FIGURE 79.8  Serial transverse enteroplasty procedure. Arrows indicate direction of stapler (open jaw) placement onto bowel. (From Kim HB, Fauza D, Garza J, Oh JT, Nurko S, Jaksic T. Serial transverse enteroplasty [STEP]: a novel bowel lengthening procedure. J Pediatr Surg. 2003;38:425–429.)

can be performed as a primary index lengthening procedure or be repeated on patients who develop dilatations after LILT or STEP operations.76,77 However, several disadvantages also exist. Asymmetrical postoperative redilation can also occur in STEP, as in LILT. This complication has been attributed to the postoperative alterations in orientation of the muscles from concentric fibers to longitudinal fibers and vice versa, making peristalsis uncoordinated, resulting in dilation.78,79 Jones et al. reported on the latest data from the International STEP Data Registry.80 He cites that of the 111 consecutive patients enrolled that the overall postoperative mortality was 11%. Expectedly, patients with longer bowel length pre-STEP were more likely to achieve enteral autonomy, with 47% of patients achieving enteral autonomy post procedure.80

SPIRAL INTESTINAL LENGTHENING AND TAILORING The latest innovation in the bowel lengthening is the spiral intestinal lengthening and tailoring (SILT). In 2013 Cserni et al. published the description of SILT successfully performed on six Vietnamese minipigs.81 This new technique entails cutting the bowel and its associated mesentery along a 45- to 60-degree spiral line, then longitudinally tightening the spiral and lengthening the bowel. The bowel edges are approximated with suture. The advantages reported are minimal manipulation to the mesentery and no changes to the orientation of the bowel fibers, which have been attributed to cause redilation after STEP (Fig. 79.9).78 The potential complications are intestinal leakage and abscess formation. No long-term data exist on this procedure because the first two applications on human patients were reported in 2014. Cserni followed his in vivo case report with the first human application on a

Since the 1960s multivisceral transplantation (MVTx) has been complicated by challenges of graft rejection, infection, and progression of underlying disease. Tacrolimus was introduced in 1989 and drastically reduced the rates of allograft rejection, hence improving surgical outcomes.83 With steady improvements in immunosuppression strategies and surgical techniques, survival rates have also improved. For intestinal and MVTx, the 1- and 3-year survival rates are reported to be 78% and 66%, respectively, with the intestinal graft survival of 80% in adults.84 In addition, Abu-Elmagd et al. report a patient survival rate after a 15-year follow-up to be as high as 61%.85 More than 90% of patients undergoing intestinal transplantation are reported to have been liberated off of TPN.86 This level of success has elevated small bowel transplantation as a final curative option in patients with intestinal failure and futile medical and surgical rehabilitation attempts, offering relief from complications associated with TPN and ultimately, a better quality of life. Since its inception in the 1990s, approximately 2887 intestinal transplants from 87 different centers have been reported. Since 2001 more than 100 intestinal transplants are performed per year, 75% in the United States.86 To date, intestinal transplantation has been performed only in situations in which no other therapeutic means are available, and as a result no randomized control study exists to compare transplantation with other surgical therapies.3 The current indications for SBTx are those SBS patients who experience IFALD, PN failure, recurrent CRIs (more than two per year, fungemia, shock, acute respiratory distress syndrome), thrombosis of two of the six major central access veins, alterations in growth and development in children, severe dehydration with refractory electrolyte changes, and impending liver failure or established liver disease with cirrhosis and portal hypertension.87,88 Depending on other associated organs needing replacement, intestinal transplantation has a number of variations. An isolated SBTx is offered in irreversible intestinal failure in the absence of concomitant liver failure proven by liver biopsy. The entire jejunum and ileum is transplanted with or without the colon, in efforts to maintain as much functional bowel as possible. Intestinal continuity is established 8 to 10 cm distal to the ligament of Treitz via side-to-side graft to native jejunojejunal anastomosis. Then a side-to-side graft ileum to native colon anastomosis approximately 15 cm from the ileostomy is created to reestablish continuity. In all of these transplant procedures, an allograft end ileostomy is performed so as to be used

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FIGURE 79.9  Spiral intestinal lengthening and tailoring procedure. (From Cserni T, Takayasu H, Muzsnay Z, et al. New idea of intestinal lengthening and tailoring. Pediatr Surg Int. 2011;27:1009–1013.)

for graft surveillance for allograft rejection via repeated biopsies if needed.59 A combined liver-intestinal transplant (SB-LTx) is performed when patients with intestinal failure also have a coexisting irreversible liver disease. A MVTx is reserved for cases in which abdominal catastrophes (i.e., extensive intestinal resection, severe abdominal trauma, multiple enterocutaneous fistulas, chronic diffuse mesenteric vascular thrombosis) necessitate a complete replacement of all abdominal organs.89 MVTx requires the removal and transplantation of both foregut and midgut. Variations include replacement of liver, kidneys, and large intestine, as well depending on the need.59 Complications associated with intestinal transplantation are vast, complex, and life-threatening and beyond the scope of this chapter. The most common complications include postoperative hemorrhage, biliary or vascular complications, and GI leaks. Biliary leak often occurs in the early postoperative period at the Roux-en-Y choledochojejunostomy in SB-LTx. Vascular complications are rare but devastating. Necrosis of the tissues results from arterial thrombosis and may necessitate graft removal. Venous thrombosis of the superior mesenteric vein or portal vein access can result in an outflow obstruction and also compromise the intestinal graft. GI leaks from

the proximal and distal anastomosis usually occur in the first postoperative week. Bleeding is the most common GI complication, and rejection of the intestinal graft must be investigated and distinguished from infection. Endoscopy is performed through the end ileostomy, and biopsies are taken to assess for rejection.90–94 Infectious etiologies of bleeding include Epstein-Barr virus (EBV) or cytomegalovirus (CMV), which can also be identified as bleeding ulcers via endoscopy. EBV infection remains one of the most serious consequences after intestinal transplantation. EBV-associated posttransplant lymphoproliferative disorder (PTLD) presents as a constellation of disorders ranging from a nonspecific, self-limiting mononucleosis to serious PTLD leading to lymphoma. PTLD incidence is higher with intestinal transplant at 20% as compared with other types of organ transplants.3 CMV is the most common viral infection after intestinal transplant and also has significant morbidity and mortality. The overall incidence is 34%, primarily involving the allograft intestine.3 CMV is diagnosed by monitoring CMV polymerase chain reaction (PCR) or culture and treated with intravenous ganciclovir or valganciclovir as first-line and foscarnet as second-line therapy.95

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SECTION II  Stomach and Small Intestine

A

B

C

D

FIGURE 79.10  Spiral intestinal lengthening and tailoring in vivo. (From Cserni T, Varga G, Erces D, et al. Spiral intestinal lengthening and tailoring—first in vivo study. J Pediatr Surg. 2013;48:1907–1913.)

Interestingly, although the survival rates mentioned previously are higher for isolated SBTx than MVTx, the risk of acute cellular rejection (ACR) is higher in SBTx (79%) when compared with combined SB-LTx (71%) or MVTx (59%), respectively.89,96 This immunologic reaction has been attributed to the highly immunogenic small bowel allograft, which contains a large amount of gutassociated lymphoid tissue, as well as donor dendritic cells that propagate an ACR.97 It has been postulated that the MVTx and the SB-LVTx have protective effects from the liver. ACR can occur any time with 48% presenting within 30 days and 66% presenting within the first 100 posttransplantation.98 Induction therapy with IL-2 blocker has become the standard of care in over 75% of intestine transplant recipients, leading to decreased incidence of acute rejection and improved patient survival.99 Protocolized surveillance endoscopies through the graft ileostomy are usually performed twice weekly for the first 4 to 6 weeks then in decreasing frequency in the following weeks following transplantation; therefore most acute rejections are discovered.100 ACR presents with diarrhea resulting in damage to the gut mucosal barrier. This barrier compromise leads to bacterial sepsis and fever. Once endoscopy and biopsies confirm the diagnosis, the patient is initially treated with a cumulative steroid dose

of 30 mg/kg methylprednisolone given in three divided doses for three days or a 10 mg/kg bolus followed by tapered doses of 5, 4, 3, and 2 mg/kg each day after. Posttreatment biopsies are performed until symptoms resolve or pathology shows histologic improvement. Steroid refractory rejection manifests as ongoing exfoliation of mucosa and persistent crypt loss on histology and will require the addition of antilymphocyte antibodies (i.e., murine anti-CD3 monoclonal antibody [OKT3]). Five to seven doses are used. Other antibody agents used are anti-CD52 humanized monoclonal antibodies (alemtuzamab) and rabbit antihuman thymocyte globulin (rATG).87 Sepsis remains the leading cause of graft loss in 50% of cases, followed by graft-related causes including rejection at 13% and cardiovascular events at 8%.

CONCLUSION Patients with SBS are a small part of the population; however, these patients have complex pathophysiologies that demand intensive long-term health care. Great prog­ ress in the survival of SBS patients occurred with the development and adoption of PN, but with raised secondary costs of an iatrogenic nature (PN-related catheter complications, nutritional deficiencies, and liver failure). The

Short Bowel Syndrome  CHAPTER 79 

success in optimizing the life span and the quality of life for SBS patients is delivered with the optimization of fluid and dietary management, education and psychosocial support, metabolic management, innovative pharmacologic nutritional additives (teduglutide), and the transition to focused surgical interventions (intestinal surgical rehab or transplantation). Better understanding of both the loss and adaptation capacity of small intestine also means an individualized program of support for each SBS patient. Further progress in the management of these patients will likely occur at the expansion of IRCs with the established clinical pathways and programmatic orientation toward these patients.

REFERENCES 1. Crenn P, Hanchie M, Valleur P, Hautefeuille P, Rambaud JC, Messing B. Surgical versus radiological evaluation of remaining small bowel length in short bowel syndrome. Gastroenterology. 1996;110:A321. 2. Nightingale JMD, Bartram CI, Lennard-Jones JE. Length of residual small bowel after partial resection: correlation between radiographic and surgical measurements. Gastrointest Radiol. 1991;16(1):305-306. 3. DeLegge M, Alsolaiman MM, Barbour E, Bassas S, Siddiqi MF, Moore NM. Short bowel syndrome: parenteral nutrition versus intestinal transplantation. Where are we today? Dig Dis Sci. 2007; 52(4):876-892. 4. Thompson J. Comparison of massive vs. repeated resection leading to short bowel syndrome. J Gastrointest Surg. 2000;4(1):101-104. 5. Chopy K, Winkler M, Schwartz-Barcott D, Melanson K, Greene G. A qualitative study of the perceived value of membership in the Oley Foundation by home parenteral and enteral nutrition consumers. JPEN J Parenter Enteral Nutr. 2014;39(4):426-433. 6. 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(3):243 -255. 7. Mughal M. Home parenteral nutrition in the United Kingdom and Ireland. Lancet. 1986;328(8503):383-387. 8. Bakker H, Bozzetti F, Staun M, et al. Home parenteral nutrition in adults: a European multicentre survey in 1997. ESPEN-Home Artificial Nutrition Working Group. Clin Nutr. 1999;18(3):135-140. 9. Brandt CF, Bangsgaard L, Jess T, et al. Mo1179 the evolution of treatment of patients with intestinal failure with home parenteral nutrition. Gastroenterology. 2012;142(5):S-613-S-614. 10. Pironi L, Hébuterne X, Van Gossum A, et al. Candidates for intestinal transplantation: a multicenter survey in Europe. Am J Gastroenterol. 2006;101(7):1633-1643. 11. Amiot A, Messing B, Corcos O, Panis Y, Joly F. Determinants of home parenteral nutrition dependence and survival of 268 patients with non-malignant short bowel syndrome. Clin Nutr. 2013;32(3): 368-374. 12. Grant D, Abu-Elmagd K, Reyes J, et al. 2003 Report of the intestine transplant registry. Ann Surg. 2005;241(4):607-613. 13. Wales PW, de Silva N, Kim J, Lecce L, To T, Moore A. Neonatal short bowel syndrome: population-based estimates of incidence and mortality rates. J Pediatr Surg. 2004;39(5):690-695. 14. 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(5):1043-1050. 15. Wales PW, Christison-Lagay ER. Short bowel syndrome: epidemiology and etiology. Semin Pediatr Surg. 2010;19(1):3-9. 16. Buchman AL. The medical and surgical management of short bowel syndrome. MedGenMed. 2004;6:12. 17. Tappenden KA. Pathophysiology of short bowel syndrome: considerations of resected and residual anatomy. JPEN J Parenter Enteral Nutr. 2014;38(1 suppl):14S-22S. 18. Kumpf V. Pharmacological management of diarrhea in patients with short bowel syndrome. JPEN J Parenter Enteral Nutr. 2014;38 (suppl 1):38S-44S.

937

19. Debongnie JC, Phillips SF. Capacity of the human colon to absorb fluid. Gastroenterology. 1978;74:698-703. 20. Keller J, Panter H, Layer P. Management of the short bowel syndrome after extensive small bowel resection. Best Pract Res Clin Gastroenterol. 2004;18(5):977-992. 21. Ulrich-Baker MG, Höllwarth ME, Kvietys PR, Granger DN. Blood flow response to small bowel resection. Am J Physiol. 1986;251:G815G822. 22. Tappenden K. Intestinal adaptation following resection. JPEN J Parenter Enteral Nutr. 2014;38(suppl 1):23S-31S. 23. Spencer AU, Neaga A, West B, et al. Pediatric short bowel syndrome: redefining predictors of success. Ann Surg. 2005;242:403-412. 24. Joly F, Mayeur C, Messing B, et al. Morphological adaptation with preserved proliferation/transporter content in the colon of patients with short bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2009;297:G116-G123. 25. Doldi S. Intestinal adaptation following jejuno-ileal bypass. Clin Nutr. 1991;10:138-145. 26. Royall D, Wolever TM, Jeejeebhoy KN. Evidence for colonic conservation of malabsorbed carbohydrate in short bowel syndrome. Am J Gastroenterol. 1992;87:751-756. 27. Nordgaard I, Hansen BS, Mortensen PB. Importance of colonic support for energy absorption as small-bowel failure proceeds. Am J Clin Nutr. 1996;64:222-231. 28. Nightingale JM, Kamm MA, van der Sijp JR, Ghatei MA, Bloom SR, Lennard-Jones JE. Gastrointestinal hormones in short bowel syndrome: peptide YY may be the “colonic brake” to gastric emptying. Gut. 1996;39:267-272. 29. Chen WJ, Yang CL, Lai HS, Chen KM. Effects of lipids on intestinal adaptation following 60% resection in rats. J Surg Res. 1995;58:253-259. 30. Byrne TA, et al. Growth hormone, glutamine, and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome. Ann Surg. 2005;242(5):655-661. 31. Wales PW, Nasr A, de Silva N, Yamada J. Human growth hormone and glutamine for patients with short bowel syndrome. Cochrane Database Syst Rev. 2010;(6):CD006321. 32. Wall E. An overview of short bowel syndrome management: adherence, adaptation and practical recommendations. J Acad Nutr Diet. 2013;113:1200-1208. 33. Nordgaard I, Hansen BS, Mortensen PB. Colon as a digestive organ in patients with short bowel. Lancet. 1994;343:373-376. 34. Torres C, Vanderhoof JA. Chronic complications of short bowel syndrome. Curr Paediatr. 2006;16(5):291-297. 35. Cavicchi M. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med. 2000;132(7):525. 36. 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. 37. Jeppesen PB, Pertkiewicz M, Forbes A, et al. Quality of life in patients with short bowel syndrome treated with the new glucagonlike peptide-2 analogue teduglutide—analyses from a randomised, placebo-controlled study. Clin Nutr. 2013;32:713-721. 38. Matarese LE, Jeppesen PB, O’Keefe SJ. Short bowel syndrome in adults: the need for an interdisciplinary approach and coordinated care. JPEN J Parenter Enteral Nutr. 2014;38(suppl 1):60S-64S. 39. Nehme A. Nutritional support of the hospitalized patient: the team concept. JAMA. 1980;243(19):1906-1908. 40. Hassell JT, Games AD, Shaffer B, Harkins LE. Nutrition support team management of enterally fed patients in a community hospital is cost-beneficial. J Am Diet Assoc. 1994;94(9):993-998. 41. Reddy VS, Patole SK, Rao S. Role of probiotics in short bowel syndrome in infants and children—a systematic review. Nutrients. 2013;5:679-699. 42. Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for the management of intravascular catheter-related infections. Infect Control Hosp Epidemiol. 2001;22(4):222-242. 43. Mouw E, Chessman K, Lesher A, Tagge E. Use of an ethanol lock to prevent catheter-related infections in children with short bowel syndrome. J Pediatr Surg. 2008;43(6):1025-1029. 44. Drongowski RA, Coran AG. An analysis of factors contributing to the development of total parenteral nutrition-induced cholestasis. JPEN J Parenter Enteral Nutr. 1989;13(6):586-589. 45. Thompson J. Surgical considerations in the short bowel syndrome. Surg Gynecol Obstet. 1993;176(1):89-101.

938

SECTION II  Stomach and Small Intestine

46. Wales PW. Surgical therapy for short bowel syndrome. Pediatr Surg Int. 2004;20(9):647-657. 47. Anagnostopoulos D, Valioulis J, Sfougaris D, Maliaropoulos N, Spyridakis J. Morbidity and mortality of short bowel syndrome in infancy and childhood. Eur J Pediatr Surg. 1991;1(5):273-276. 48. Puntis JWL, Booth IW, Buick R. Cisapride in neonatal short gut. Lancet. 1986;328(8498):108-109. 49. Nightingale JMD. Management of patients with a short bowel. Nutrition. 1999;15(7-8):633-637. 50. Barksdale EM, Stanford A. The surgical management of short bowel syndrome. Curr Gastroenterol Rep. 2002;4(3):229-237. 51. Warner BW, Chaet MS. Nontransplant surgical options for management of the short bowel syndrome. J Pediatr Gastroenterol Nutr. 1993;17(1):1-12. 52. Jones BA, Hull MA, McGuire MM, Kim HB. Autologous intestinal reconstruction surgery. Semin Pediatr Surg. 2010;19(1):59-67. 53. Thompson JS. The role of prophylactic cholecystectomy in the short-bowel syndrome. Arch Surg. 1996;131(5):556. 54. Scolapio JS, Fleming CR. Short bowel syndrome. Gastroenterol Clin North Am. 1998;27(2):467-479. 55. Thompson JS. Surgical rehabilitation of intestine in short bowel syndrome. Surgery. 2004;135(5):465-470. 56. Andorsky DJ, Lund DP, Lillehei CW, et al. Nutritional and other postoperative management of neonates with short bowel syndrome correlates with clinical outcomes. J Pediatr. 2001;139(1):27-33. 57. Beyer-Berjot L, Joly F, Maggiori L, et al. Segmental reversal of the small bowel can end permanent parenteral nutrition dependency: an experience of 38 adults with short bowel syndrome. Ann Surg. 2012;256(5):739-745. 58. Vernon AH, Georgeson KE. Surgical options for short bowel syndrome. Semin Pediatr Surg. 2001;10(2):91-98. 59. Rege A. The surgical approach to short bowel syndrome—autologous reconstruction versus transplantation. Viszeralmedizin. 2014;30(3): 179-189. 60. de Lorimier AA, Harrison MR. Intestinal plication in the treatment of atresia. J Pediatr Surg. 1983;18(6):734-737. 61. Thompson JS, Langnas AN, Pinch LW, Kaufman S, Quigley EM, Vanderhoof JA. Surgical approach to short-bowel syndrome. Ann Surg. 1995;222(4):600-607. 62. King B, et al. Intestinal bowel lengthening in children with short bowel syndrome: systematic review of the Bianchi and STEP procedures. World J Surg. 2012;37(3):694-704. 63. Bianchi A. Intestinal loop lengthening—a technique for increasing small intestinal length. J Pediatr Surg. 1980;15(2):145-151. 64. Boeckman CR, Traylor R. Bowel lengthening for short gut syndrome. J Pediatr Surg. 1981;16(6):996-997. 65. Bianchi A. From the cradle to enteral autonomy: the role of autologous gastrointestinal reconstruction. Gastroenterology. 2006;130(2):S138-S146. 66. Goulet O, Sauvat F. Short bowel syndrome and intestinal transplantation in children. Curr Opin Clin Nutr Metab Care. 2006;9(3):304-313. 67. Thompson J, Sudan D. Intestinal lengthening for short bowel syndrome. Adv Surg. 2008;42:49-61. 68. Thompson JS, Vanderhoof JA, Antonson DL. Intestinal tapering and lengthening for short bowel syndrome. J Pediatr Gastroenterol Nutr. 1985;4(3):495-497. 69. Kimura K, Soper RT. A new bowel elongation technique for the short-bowel syndrome using the isolated bowel segment Iowa models. J Pediatr Surg. 1993;28(6):792-794. 70. Yamazato M, Kimura K, Yoshino H, Soper RT. The isolated bowel segment (Iowa model II) created in functioning bowel. J Pediatr Surg. 1991;26(7):780-783. 71. El-Murr M, Kimura K, Ellsberg D, Yamazato M, Yoshino H, Soper RT. Motility of isolated bowel segment Iowa model III. Dig Dis Sci. 1994;39(12):2619-2623. 72. Weber TR. Isoperistaltic bowel lengthening for short bowel syndrome in children. Am J Surg. 1999;178(6):600-603. 73. Kim HB, Fauza D, Garza J, Oh JT, Nurko S, Jaksic T. Serial transverse enteroplasty (STEP): a novel bowel lengthening procedure. J Pediatr Surg. 2003;38(3):425-429.

74. Kim HB, Lee PW, Garza J, Duggan C, Fauza D, Jaksic T. Serial transverse enteroplasty for short bowel syndrome: a case report. J Pediatr Surg. 2003;38(6):881-885. 75. Sigalet D. STEP procedure. Oper Tech Gen Surg. 2007;9(1):39-42. 76. Ehrlich PF, Mychaliska GB, Teitelbaum DH. The 2 STEP: an approach to repeating a serial transverse enteroplasty. J Pediatr Surg. 2007;42(5):819-822. 77. Andres AM, Thompson J, Grant W, et al. Repeat surgical bowel lengthening with the STEP procedure. Transplantation. 2008;85(9): 1294-1299. 78. Cserni T, Takayasu H, Muzsnay Z, et al. New idea of intestinal lengthening and tailoring. Pediatr Surg Int. 2011;27(9):1009-1013. 79. Kang KH, Gutierrez IM, Zurakowski D, et al. Bowel re-dilation following serial transverse enteroplasty (STEP). Pediatr Surg Int. 2012;28(12):1189-1193. 80. Jones BA, Hull MA, Potanos KM, et al. Report of 111 consecutive patients enrolled in the International Serial Transverse Enteroplasty (STEP) Data Registry: a retrospective observational study. J Am Coll Surg. 2013;216(3):438-446. 81. Cserni T, Varga G, Erces D, et al. Spiral intestinal lengthening and tailoring—first in vivo study. J Pediatr Surg. 2013;48(9):1907-1913. 82. Alberti D, Boroni G, Giannotti G, et al. “Spiral intestinal lenghtening and tailoring (SILT)” for a child with severely short bowel. Pediatr Surg Int. 2014;30(11):1169-1172. 83. Tocci MJ, Matkovich DA, Collier KA, et al. The immunosuppressant FK506 selectively inhibits expression of early T cell activation genes. J Immunol. 1989;143(2):718-726. 84. Smith JM, Skeans MA, Horslen SP, et al. OPTN/SRTR 2012 Annual Data Report: Intestine. Am J Transplant. 2014;14(S1):97-111. 85. Abu-Elmagd KM, Kosmach-Park B, Costa G, et al. Long-term survival, nutritional autonomy, and quality of life after intestinal and multivisceral transplantation. Ann Surg. 2012;256(3):494-508. 86. Abu–Elmagd KM. Intestinal transplantation for short bowel syndrome and gastrointestinal failure: current consensus, rewarding outcomes, and practical guidelines. Gastroenterology. 2006;130(2):S132-S137. 87. Vianna RM, Mangus RS, Tector AJ. Current status of small bowel and multivisceral transplantation. Adv Surg. 2008;42:129-150. 88. Sudan D. The current state of intestine transplantation: indications, techniques, outcomes and challenges. Am J Transplant. 2014;14(9): 1976-1984. 89. Nishida S, Hadjis NS, Levi DM, et al. Intestinal and multivisceral transplantation after abdominal trauma. J Trauma. 2004;56(2):323327. 90. Fishbein TM, Gondolesi GE, Kaufman SS. Intestinal transplantation for gut failure. Gastroenterology. 2003;124(6):1615-1628. 91. Farmer DG, McDiarmid SV, Yersiz H, et al. Outcomes after intestinal transplantation: a single-center experience over a decade. Transplant Proc. 2002;34(3):896-897. 92. Reyes J, Bueno J, Kocoshis S, et al. Current status of intestinal transplantation in children. J Pediatr Surg. 1998;33(2):243-254. 93. Reyes J, Abu-Elmagd K. Small bowel transplantation in children. In: Kelly DA, ed. Diseases of the Liver and Biliary System in Children. Oxford: Wiley-Blackwell; 1999:402-420. 94. Langnas AN, Shaw BW Jr, Antonson DL, et al. Preliminary experience with intestinal transplantation in infants and children. Pediatrics. 1996;97(4):443-448. 95. Florescu DF, Abu-Elmagd K, Mercer DF, Qiu F, Kalil AC. An international survey of cytomegalovirus prevention and treatment practices in intestinal transplantation. Transplantation. 2014;97(1):78-82. 96. Donohoe CL, Reynolds JV. Short bowel syndrome. Surgeon. 2010;8(5): 270-279. 97. Nayyar N, et al. Pediatric small bowel transplantation. Semin Pediatr Surg. 2010;19(1):68-77. 98. Lee RG, et al. Pathology of human intestinal transplantation. Gastroenterol. 1996;110(6):1820-1834. 99. Israni AK, et al. OPTN/SRTR 2011 annual data report: deceased organ donation. Am J Transplant. 2012;13:179-198. 100. Garau P, et al. Pancreatitis associated with olsalazine and sulfasalazine in children with ulcerative colitis. J Pediatr Gastroenterol Nutr. 1994;18(4):481-485.