Short-Bowel Syndrome

Background
The average length of the adult human small intestine is approximately 600 cm, as calculated from studies performed on cadavers. According to Lennard-Jones and to Weser, this figure ranges from 260-800 cm.[1] Any disease, traumatic injury, vascular accident, or other pathology that leaves less than 200 cm of viable small bowel or results in a loss of 50% or more of the small intestine places the patient at risk for developing short-bowel syndrome. Short-bowel syndrome is a disorder clinically defined by malabsorption, diarrhea, steatorrhea, fluid and electrolyte disturbances, and malnutrition. The final common etiologic factor in all causes of short-bowel syndrome is the functional or anatomic loss of extensive segments of small intestine so that absorptive capacity is severely compromised. Although resection of the colon alone typically does not result in short-bowel syndrome, the condition's presence can be a critical factor in the management of patients who lose significant amounts of small intestine.[2, 3] Massive small intestinal resection compromises digestive and absorptive processes. Adequate digestion and absorption cannot take place, and proper nutritional status cannot be maintained without supportive care. Today, the most common causes of short-bowel syndrome in adults include Crohn disease,[4] radiation enteritis, mesenteric vascular accidents, trauma, and recurrent intestinal obstruction. In the pediatric population, necrotizing enterocolitis, intestinal atresias, and intestinal volvulus are the most common etiologic factors. Other conditions associated with short-bowel syndrome include congenital short small bowel, gastroschisis, and meconium peritonitis. Not all patients with loss of significant amounts of small intestine develop short-bowel syndrome. Important cofactors that help to determine whether the syndrome will develop or not include the premorbid length of small bowel, the segment of intestine that is lost, the age of the patient at the time of bowel loss, the remaining length of small bowel and colon, and the presence or absence of the ileocecal valve.

History of the Procedure

Several operative or invasive procedures and therapies have been designed for and applied to the treatment of short-bowel syndrome. These include the establishment of central venous access for delivery of total parenteral nutrition, intestinal transplantation, and nontransplantation abdominal operations. The history of these various treatment strategies is discussed in this section. Total parenteral nutrition was developed successfully by Dudrick et al.[5] Their landmark paper included laboratory studies in a canine model and clinical results in 30 adult patients with a variety of gastrointestinal maladies ranging from achalasia to traumatic pancreatitis to regional enteritis. The animal model clearly demonstrated efficacy. Beagle puppies fed entirely intravenously surpassed their littermate controls in weight gain and were equal in terms of activity level, skeletal growth, and other developmental landmarks. In the clinical arm of the

study, the 30 subjects receiving total parenteral nutrition were able to achieve positive nitrogen balance, maintain weight, heal wounds, and close fistulae. Wilmore and Dudrick reported positive nitrogen balance, growth, and development in an infant born with diffusely atretic small bowel who was fed entirely parenterally.[6] After these initial successes, the new technique was introduced into the clinical mainstream, and indications for its use have expanded tremendously. Patients with short-bowel syndrome are now routinely treated with total parenteral nutrition, especially early in their course. New therapeutic strategies that may allow patients to discontinue or curtail the use of total parenteral nutrition are discussed in subsequent sections. Numerous nontransplant operative approaches have been used in the treatment of patients with short-bowel syndrome. The creation of reversed intestinal segments was popular in the 1960s and 1970s. The aim of this operation was to produce a sort of functional partial small bowel obstruction that would slow intestinal transit time, thereby encouraging greater nutrient absorption and decreasing diarrhea and nutrient loss. Around that time, recirculating small bowel loops were also being created, with the same idea in mind. The results were mixed to questionable, and these procedures are rarely used today. Intestinal lengthening (Bianchi procedure), the creation of artificial enteric valves, strictureplasty, and intestinal tapering procedures continue to be employed at some centers today. Intestinal transplantation was first attempted in dogs in 1959. The procedures failed because of the great concentration of immune system cells associated with the gut. The discovery and clinical implementation of powerful immunosuppressive drugs, such as FK506 (tacrolimus) and cyclosporine A, made successful small bowel transplantation possible. The first successful combined transplantation of small intestine and liver in a human was performed in 1990. Since that time, the technique of isolated small intestinal transplantation has been developed and applied. Better graft survival rates are achieved when patients receive their transplant before complications secondary to short gut syndrome occur, especially that of cirrhosis.[7]

Problem
Each year in the United States, many patients undergo resection of long segments of small intestine for various disorders, including inflammatory bowel disease, malignancy, mesenteric ischemia, and others. Juvenile survivors of necrotizing enterocolitis, midgut volvulus, and other abdominal catastrophes are becoming more common. Various nonoperative procedures can leave patients with a functional short-bowel syndrome. An example of this clinical scenario is radiation enteritis. Those patients who are left with insufficient small bowel absorptive surface area develop malabsorption, malnutrition, diarrhea, and electrolyte abnormalities. The subset of patients with clinically significant malabsorption and malnutrition are said to have developed short-bowel syndrome.

Epidemiology
Frequency

Estimates of the incidence and prevalence of short-bowel syndrome are difficult to make and, therefore, are rare. Most estimates are based on data describing patients requiring long-term home parenteral nutrition for short-bowel syndrome. A report by Lennard-Jones estimated that in the United Kingdom, the incidence of short-bowel syndrome requiring such therapy was 2 patients per million population.[8] Byrne et al estimated that in the United States, approximately 10,000-20,000 patients receive home-delivered total parenteral nutrition for short-bowel syndrome.[9] Moreno and coworkers published data derived from the 2002 registry of patients receiving home-based parenteral nutrition in Spain.[10] The program had an enrollment of 74 patients, making the prevalence in Spain 1.8 patients per 1 million population.

Etiology
In the first decades of the twentieth century, bowel strangulation and midgut volvulus were the most common etiologies resulting in short-bowel syndrome. By the 1950s and 1960s, mesenteric vascular accidents, including thrombosis and embolism of the superior mesenteric artery, had become the most common causes of short-bowel syndrome. Jejunoileal bypass procedures once were popular for the treatment of morbid obesity. However, they produced an iatrogenic short gut syndrome and the attendant metabolic and hepatic complications associated with chronic malabsorption. These procedures have since been abandoned. Studies by Ladefoged and colleagues and Nightingale and Lennard-Jones found that Crohn disease has become the most common etiology of short-bowel syndrome in adults, accounting for 50-60% of cases.[11, 12] Other important causative entities include mesenteric ischemia and radiation enteritis. In contrast, the Spanish home parenteral nutrition registry data reported by Moreno and colleagues described mesenteric ischemia as the leading cause of short-bowel syndrome (29.7%), followed by neoplastic diseases (16.2%), radiation enteritis (12.2%), motility disorders (8.1%), and Crohn disease (5.4%).[10] Occasionally, trauma that involves 1 or more of the major mesenteric vessels results in extensive bowel necrosis and short-bowel syndrome. Leading pediatric and neonatal etiologies of short-bowel syndrome include necrotizing enterocolitis, multi-level small bowel atresia, and midgut volvulus with ischemic bowel infarction.

In a study of 114 infants with jejunoileal atresia, Stollman et al found that surgical treatment (which included resection with primary anastomosis in 69% of the children and temporary enterostomy in 26% of them) resulted in short-bowel syndrome in 15% of the patients.[13] This led the investigators to suggest that short-bowel syndrome is the chief factor behind longer hospital stays for and increased feeding problems and rates of morbidity and mortality in infants who are surgically treated for jejunoileal atresia.

Pathophysiology
Physiologic derangements in short-bowel syndrome are the result of the loss of large amounts of intestinal absorptive surface area. The sequelae of this loss include malabsorption of water, electrolytes, macronutrients (ie, proteins, carbohydrates, fats), and micronutrients (ie, vitamins, minerals, trace elements). The gastrointestinal tract is a vital locus for water and electrolyte absorption and transport. In addition to managing exogenously obtained sources of these nutrients, such as daily water intake and the electrolytes found in liquid and solid foods, the gastrointestinal tract must deal with its own considerable daily secretions. The monumental nature and efficiency of this task is illustrated by Sellin.[14] He describes that the gastrointestinal tract processes 8000-9000 mL of fluid per day, with the vast majority of this derived from endogenous secretions. Fluid reabsorption by the healthy gastrointestinal tract is efficient (98%), and only 100-200 mL are lost in fecal matter each day. The great majority (80%) of this reabsorption occurs in the small intestine. Disturbances in the major determinants of intestinal fluid absorption negatively impact the ability to reabsorb this large fluid load. The major determinants include intestinal mucosal surface area, the health or integrity of the mucosa, the status of small bowel motility, and the osmolarity of solutes in the intestinal lumen. Clinically, these disturbances can manifest as major components of short-bowel syndrome, namely diarrhea, dehydration, and electrolyte imbalance. Thus, shortbowel syndrome can be produced by clinical entities that result in critical loss of mucosal surface area (eg, massive small bowel resection) or degrade mucosal integrity (eg, radiation enteritis). Macronutrients and micronutrients are absorbed along the length of the small intestine. However, as described by Clarke, the jejunum has taller villi, deeper crypts, and greater enzyme activity compared to the ileum.[15] Therefore, under normal conditions, about 90% of digestion and absorption of significant macronutrients and micronutrients are accomplished in the proximal 100-150 cm of the jejunum according to work conducted by Borgstrom and colleagues and by Johansson.[16, 17] This includes absorption of proteins; carbohydrates; fats; vitamins B, C, and folic acid; and the fat-soluble vitamins A, D, E, and K. However, if a significant portion or all of the jejunum is resected, the absorption of proteins, carbohydrates, and most vitamins and minerals can be unaffected because of adaptation in the ileum. Unfortunately, enzymatic digestion suffers because of the irreplaceable loss of enteric hormones produced by the jejunum. Biliary and pancreatic secretions decrease. Gastrin levels rise, causing gastric hypersecretion. The resultant high acid output from the stomach may injure the small bowel mucosa. Additionally, the low intraluminal pH creates unfavorable conditions

for optimal activity of the pancreatic enzymes that are present. Diarrhea may then result if a large osmotically active solute load of unabsorbed nutrients is delivered to the ileum and colon. Ileal resection severely decreases the capacity to absorb water and electrolytes. In addition, the terminal ileum is the site of absorption of bile salts and vitamin B-12. Loss of significant lengths of ileum almost invariably results in diarrhea. Continued loss of bile salts following resection of the terminal ileum leads to fat malabsorption, steatorrhea, and loss of fat-soluble vitamins. Retention of the ileocecal valve plays a pivotal role in massive small bowel resection. If the ileocecal valve can be preserved, intestinal transit is slowed, allowing more time for absorption. If the ileocecal valve is lost, transit time is faster, and loss of fluid and nutrients is greater. Furthermore, colonic bacteria can colonize the small bowel, worsening diarrhea and nutrient loss. Preservation of the colon has positive and negative attributes. Philips and Giller demonstrated that colonic water absorption could be increased to as much as 5 times its normal capacity following small bowel resection.[18] Also, by virtue of its resident bacteria, the colon has the inherent capacity to metabolize undigested carbohydrates into short-chain fatty acids, such as butyrate, propionate, and acetate. These are a preferred fuel source for the colon. Interestingly, work by Pomare and colleagues and Halverstad demonstrated that the colon can absorb up to 500 kcal daily of these metabolites, which then can be transported via the portal vein to be used as a somatic fuel source.[19] In contrast, maintenance of the colon increases the incidence of urinary calcium oxalate stone formation. The oxalate is normally bound by calcium in the small bowel and, thus, is insoluble when it reaches the colon. After massive enterectomy, much of this calcium is bound by free intraluminal fats. Free oxalate is delivered to the colon, where it is absorbed. This can eventually lead to saturation of the urine with calcium oxalate crystals and result in stone formation. As mentioned above, retention of the colon in the absence of a competent ileocecal valve can lead to small intestinal bacterial overgrowth. The physiologic changes and adaptation of patients with short-bowel syndrome can be viewed in 3 phases.[20] The acute phase occurs immediately after massive bowel resection and may last up to 3-4 months. The acute phase is associated with malnutrition and fluid and electrolyte loss through the gastrointestinal tract. Fluid and electrolyte loss through the gastrointestinal tract may be as high as 6-8 L/d. Patients will have abnormal liver function test results and transient hyperbilirubinemia. Enteral feedings may also be initiated, but it should be relatively slow. Patients with less than 100 cm of small intestine will require total parenteral nutrition. The presence of ileocecal valve or colon may play a significant role in the outcome of these patients.[20] The adaptation phase generally begins 2-4 days after bowel resection and may last up to 12-18 months.[20] During this second phase, up to 90% of the bowel adaptation may occur. Villous hyperplasia, increased crypt depth, and intestinal dilatation occur. Early continuous feedings with a high viscosity elemental diet may reduce the duration of total parenteral nutrition.[20]

In the maintenance phase, the absorptive capacity of the gastrointestinal tract is at its maximum.[20] Some patients may still require total parenteral nutrition. In other patients, nutritional and metabolic homeostasis can be achieved by small meals and supplemental nutritional support for life. These patients will also require vitamins and mineral supplements, including vitamins A, B-12, and D, magnesium, and zinc.[20] A summary of the 3 phases is outlined below.

Acute phase o Starts immediately after bowel resection and lasts 1-3 months o Ostomy output of greater than 5 L/d o Life-threatening dehydration and electrolyte imbalances o Extremely poor absorption of all nutrients o Development of hypergastrinemia and hyperbilirubinemia Adaptation phase o Begins within 48 hours of resection and lasts up to 1-2 years o Approximately 90% of the bowel adaptation takes place during this phase. o Enterocyte hyperplasia, villous hyperplasia, and increased crypt depth occur, resulting in increased surface area. Intestinal dilatation and lengthening also occur. o Luminal nutrition is essential for adaptation and should be initiated as early as possible. Parenteral nutrition is also essential throughout this period. Maintenance phase o The absorptive capacity of the intestine is at its maximum. o Nutritional and metabolic homeostasis can be achieved by oral feeding, or patients are committed to receiving supplemental or complete nutritional support for life.

Presentation
Patients with short-bowel syndrome invariably present with a history of several intestinal resections, as occurs with Crohn disease, or with a history of a major abdominal catastrophe or vascular accident, such as midgut volvulus or embolus to the superior mesenteric vessels. Pursuant to the resultant malabsorption, diarrhea (with or without steatorrhea) is an almost constant clinical finding. Patients with short-bowel syndrome may describe significant weight loss, fatigue, malaise, and lethargy. These symptoms are protean but consistent with the diarrheic diathesis and resultant dehydration, electrolyte imbalance, protein-calorie malnutrition, and loss of critical vitamins and minerals. Vitamin and mineral deficiencies can lead to some specific symptoms. Patients with vitamin A deficiencies may report night blindness and xerophthalmia. Vitamin D depletion can be associated with paresthesias and tetany. Loss of vitamin E can cause paresthesias, ataxic gait, and visual disturbances because of retinopathy. A history of easy bruisability or prolonged bleeding might suggest vitamin K depletion. Patients reporting dyspnea on exertion or lethargy may be anemic from vitamin B-12, folic acid, or iron deficiency. Calcium and magnesium losses can cause paresthesias and tetany. Patients with critically low zinc levels may describe anorexia and diarrhea.

Physical examination of the patient with short-bowel syndrome can reveal many clues to the diagnosis, depending on the duration and severity of the malabsorption.

Patients who are severely protein and energy malnourished may present with temporal wasting, loss of digital muscle mass, and peripheral edema. The skin may be dry and flaky. The nails can feature prominent ridges, and the lingual papillae are blunted or atrophic. In children, poor growth performance is a telling feature. The essential fatty acids are linoleic and linolenic acids. Patients with essential fatty acid deficiency experience growth retardation, dermatitis, and alopecia. The physical features of vitamin A deficiency include corneal ulcerations and growth delays. Patients with low levels of the B complex vitamins in general can present with stomatitis, cheilosis, and glossitis. Vitamin B-1 deficiency is associated with edema, tachycardia, ophthalmoplegia, and depressed deep tendon reflexes. Vitamin B-6 deficiency can cause peripheral neuropathies and seizures. Peripheral neuropathy can be a feature of B-12 deficiency also. Vitamin D depletion is associated with poor growth and bowed extremities. Severe vitamin E deficiencies can result in ataxia, edema, and depressed deep tendon reflexes. The physical hallmarks of vitamin K deficiency are related to derangements in hemostasis. These include petechiae, ecchymoses, purpura, or outright bleeding diatheses. Physical clues to the presence of iron deficiency include pallor, spooned nails, and glossitis. Zinc deficiency causes angular stomatitis, poor wound healing, and alopecia. Also, a scaly erythematous rash can erupt around the mouth, eyes, nose, and perineum.

Indications
Most survivors of massive bowel resections who develop short-bowel syndrome are initially fed with total parenteral nutrition. In these patients, total parenteral nutrition prevents the development of malnutrition and has been shown to benefit patient outcomes. Total parenteral nutrition may be administered concurrently with enteral nutrition early in the clinical course of short-bowel syndrome because the ultimate goal in many of these patients is to enhance intestinal adaptation and render patients free of total parenteral nutrition as described by Wilmore and colleagues in animal models.[21] In many patients, intestinal adaptation, alone or in combination with modified and supplemented diets (eg, growth hormone, glutamine, high carbohydrate, low fat) as described by Byrne and colleagues, eventually allows liberation from total parenteral nutrition.[9] Unfortunately, some patients are extremely difficult or impossible to wean from parenteral nutrition. Common characteristics of these patients include very short remaining small bowel segments (< 60 cm), loss of the colon, loss of the ileocecal valve, or small bowel strictures with stasis and bacterial overgrowth. Total parenteral nutrition is not a panacea. Access sites become infected or the cannulated vein thromboses, necessitating replacement. Eventually, the patient may run out of usable veins for access to deliver total parenteral nutrition. Other than these mechanical and infectious complications, many serious metabolic complications are associated with long-term use of total parenteral nutrition. The most clinically important of

these are hepatic and biliary derangements. In fact, according to Vanderhoof, advanced liver disease currently is the most common cause of death of patients with short-bowel syndrome.[22] Early in the course of therapy with total parenteral nutrition, nonspecific elevations in hepatic transaminases can be found. Frequently, these biochemical abnormalities are self-limited and require no specific alteration or curtailment of therapy. The most frequent manifestation of hepatobiliary disease in patients with short-bowel syndrome who are on total parenteral nutrition is cholestasis, as described by Cavicchi and coworkers, Klein and Nealon, and Quigley and colleagues.[23, 24, 25, 26] Biliary sludge or gallstones are found in approximately 50% of patients receiving total parenteral nutrition with no oral intake for 3 months. Progressive hepatic parenchymal damage is the most feared hepatobiliary complication of prolonged delivery of total parenteral nutrition. Fatty liver is observed frequently in adults. Nonalcoholic steatohepatitis has features of fatty change but is associated with inflammatory cell infiltration and fibrosis. Progressive cholestasis and liver injury can lead to outright portal fibrosis or cirrhosis. This portends progression to liver failure and a poor outcome. Patients with persistent liver function abnormalities should be identified before progression to cirrhosis to assess their candidacy for intestinal transplantation. Moreno and coauthors reported complication rates and survival data for their cohort of 74 patients maintained on long-term home parenteral nutrition for the short-bowel syndrome.[10] There were 94 significant complications in the group, with the majority being infectious in nature. At the end of the year, 74.3% of the patients remained on total parenteral nutrition. The most common cause for termination of support in the other 23.6% of the group was death (52.9%). Others either were switched to enteral nutritional support (11.8%) or were able to be liberated from specialized nutritional support to return to an oral diet (23.5%).

Relevant Anatomy
The gross anatomy of the small and large bowel and their arterial blood supplies are discussed in this section. The anatomic features peculiar to the small bowel and multivisceral transplantation are briefly described. Pansky stated that the duodenum extends form the pylorus to the duodenojejunal flexure and is about 25 cm in overall length.[27] At the upper left border of the second lumbar vertebra is the duodenojejunal flexure. Here the duodenum turns anteriorly and caudally to become the jejunum just distal to the ligament of Treitz. The small bowel is divided relatively arbitrarily into the jejunum (proximal two fifths) and ileum (distal three fifths), although grossly the jejunum may appear to be of greater caliber, with a slightly thicker wall. It is fixed to the retroperitoneum by the root of the mesentery, which extends from the left upper quadrant of the abdomen to the right lower quadrant. The terminal ileum is located in the right lower quadrant. The ileocecal valve marks the transition from small intestine to large intestine. The first portion of the colon is called the

cecum. The ascending colon climbs along the right paracolic gutter and bends toward the midline at the hepatic flexure. Here the transverse colon begins and makes its way to the splenic flexure where the colon angles slightly medially and also inferiorly to become the descending colon. As the descending colon crosses the pelvic brim, it becomes the sinuous sigmoid colon. This portion of the colon heads toward the midline and then proceeds inferiorly. Below the pelvic peritoneal reflection, the sigmoid colon becomes the rectum. The blood supply to the duodenum is extensive and is derived from branches of both the celiac axis and the superior mesenteric artery. These include, but are not limited to, the gastroduodenal artery, the superior and inferior pancreaticoduodenal arteries, the right gastroepiploic artery, and the supraduodenal and retroduodenal arteries. This dual blood supply helps to preserve the duodenum in the event of sudden occlusion of the superior mesenteric artery. While their blood supply is rich, the jejunum, with the exception of its proximal few centimeters, and ileum depend solely on branches of the superior mesenteric artery. These are termed the jejunal and ileal, or intestinal, arteries. The ileocolic artery, a branch of the superior mesenteric artery, also supplies the terminal ileum. The ileocolic artery and the right colic artery supply the cecum and the ascending colon. The dominant blood supply of the proximal two thirds of the transverse colon is the middle colic artery. All of these colic arteries are branches of the superior mesenteric artery. Thus, the entire midgut, from jejunum to mid transverse colon, is dependent on the superior mesenteric artery. Branches of the left colic artery, which is derived from the inferior mesenteric artery, supply the distal transverse colon and the descending colon. The sigmoid arteries and the superior rectal artery are derived from the inferior mesenteric artery as well. For an exhaustive exegesis on the anatomy and the techniques of multivisceral abdominal organ transplantation, see The Many Faces of Multivisceral Transplantation by Starzl and colleagues.[28]

Contraindications
No firm absolute contraindications to surgery exist in patients with short-bowel syndrome. The only exception to this might be the creation of a small intestinal valve, designed to increase transit time, in a patient who already has stasis or bacterial overgrowth. Patients who are severely malnourished with very low albumin or prealbumin levels and those with systemic sepsis or with severe coagulopathy because of advanced liver disease should have these conditions corrected before undergoing surgery. The decision to operate on a patient with short-bowel syndrome requires great judgment. Surgery is undertaken in these patients usually only after all other therapeutic options, such as parenteral and enteral nutrition or pharmacologic bowel compensation, have been exhausted. Others may require operation because of the complications of prolonged parenteral nutrition or stasis of enteric contents and bacterial overgrowth.

Laboratory Studies

Complete blood cell count: The complete blood cell count is an important laboratory test in the workup of the patient with short-bowel syndrome. The primary reason to order this test is to determine if the patient is anemic. The type of anemia can correlate with specific nutritional deficiencies. These include the hypochromic microcytic anemia typical of depleted iron stores and the megaloblastic anemia associated with vitamin B-12 deficiency. Albumin o The plasma albumin level is an important indicator of overall nutritional status. This protein has a half-life of approximately 21 days. Evidence is accumulating that severely depressed albumin levels, especially below 2.5 g/dL, are associated with increased rates of major morbidity and mortality in surgical patients. o In addition, albumin is a good indicator of hepatic protein synthesis. Note that during periods of stress or infection, the liver produces acute phase reactants (eg, C-reactive protein) in preference to albumin. o In contrast to the above, an abnormally elevated albumin level may be observed rarely and is consistent with dehydration. Prealbumin o Prealbumin is a good indicator of acute nutritional status. Its half-life is approximately 35 days. Many nutrition support practitioners use this protein to monitor the efficacy of nutrition support regimens in their patients. Because of the relatively short half-life, it is not a good nutritional screening tool. Albumin is better for this purpose. o Prealbumin levels can also be skewed by hydration status and renal function. Liver enzymes o Hepatocellular enzymes (eg, aspartate aminotransferase [AST], alanine aminotransferase [ALT]) are important to monitor, especially in patients receiving longterm parenteral nutritional support. Many patients on long-term parenteral nutritional support have transient elevations of these enzymes that subsequently normalize, especially as they begin or increase oral food intake. o Concern should be raised when patients have persistent elevation of the enzymes, especially when they continue to increase. This is the group of patients that may progress to true histologic hepatocellular damage, cirrhosis, and liver failure. Bilirubin: Serum bilirubin is a good indicator of liver function, but its sensitivity for early liver damage probably is less than that of the hepatocellular enzymes. Serum chemistries: Measure standard serum chemistries, including sodium, potassium, chloride, and carbon dioxidecombining power, frequently in patients on long-term parenteral nutrition. Total parenteral nutrition is commonly associated with disturbances in these values, and simple adjustments in the concentration of these are usually sufficient to correct the problem. BUN: BUN determinations are important because they provide an indication of renal reserve or function. More importantly, in this patient group, rising BUN levels may indicate that the patient is being overfed with protein. Alternately, if BUN levels are disproportionately elevated in relation to creatinine (>20:1), the patient may be dehydrated. Creatinine: Serum creatinine is a good indicator of renal function. Rising creatinine should raise concern about deteriorating renal function and may necessitate changes in the nutrition support regimen. Serum calcium, magnesium, and phosphorus: The divalent cations calcium and magnesium and the anion phosphorus are important in several cellular processes. Calcium and magnesium

participate in the function of many enzyme systems, regulate membrane stabilization and excitation, and serve important functions in cardiac conduction and other areas. Phosphorus, in the form of phosphates, and proteins are the major intracellular anions. Phosphorus is also involved in the generation of adenosine triphosphate (ATP), the major energy substrate of aerobic cells. Suspect loss of these ions in patients with severe diarrhea, especially steatorrhea. Nitrogen balance o Calculation of nitrogen balance allows the clinician to investigate whether adequate amounts of protein are being supplied to a particular patient. To perform this test, a 24hour urine collection is obtained, and the amount of urinary urea nitrogen (UUN) is measured. The amount of protein (Pr) the patient is being fed is a known variable (g Pr). These values are applied to the following equation: nitrogen balance = g Pr/6.25 - [UUN + 4g]. For every 6 g of protein, 1 g of nitrogen is present. The figure 4 g is for fecal losses. The fecal protein loss can be much higher in patients with short-bowel syndrome, malabsorption, and diarrhea. o Attaining positive nitrogen balance is important. It is associated with proper immune function, good wound healing, replenishment of lean body mass in previously catabolic patients, and growth in children. Serum vitamin levels: Vitamin levels can be measured. This is achieved best when a specific abnormality that can be attributed to a vitamin deficiency is suspected on clinical grounds. The findings associated with various vitamin deficiencies are discussed in the Clinical section. Treat vitamin deficiency by supplementation of that vitamin. Serum minerals and trace element levels o Levels of zinc, chromium, selenium, and other important minerals and trace elements can be measured. Most of these elements serve as cofactors in various metalloenzyme systems. Their depletion leads to degradation in enzyme function and, sometimes, serious clinical sequelae, some of which have been described in the Clinical section. o Treat a deficiency in one of these elements by replenishment, especially if a related clinical disorder (eg, glucose intolerance and chromium deficiency) is present. Coagulation profile: Hepatic synthesis of the proteins of the coagulation cascade is a highly conserved function. Deficient hepatic production of coagulation factors is usually a sign of advanced liver disease. Assess the international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) in all patients who are considered candidates for surgery, especially those with any evidence of liver dysfunction. Identification of a defect should lead to replacement therapy (eg, vitamin K, fresh frozen plasma [FFP]).

Imaging Studies

Chest radiograph: Obtain a chest radiograph routinely in all patients who undergo placement of a temporary or durable central venous catheter for hyperalimentation or other purposes. The chest radiograph is obtained to ensure that no complications (eg, pneumothorax) have occurred. In addition, it allows documentation of proper placement of the catheter tip (ie, in the vicinity of the superior vena cava [SVC]right atrial junction). Plain abdominal radiograph: The plain abdominal radiograph allows a preliminary assessment of bowel status. Signs of ileus or obstruction, such as greatly dilated bowel, can be looked for. Upper gastrointestinal series with small bowel follow-through: Contrast studies are a more sensitive imaging choice than the plain radiograph. The small bowel should appear somewhat dilated because this is one of the major mechanisms of small bowel adaptation. Areas of

stricturing appear as significant narrowing. Look for these especially at areas of known previous anastomoses. Overall, the bowel mucosal pattern should remain relatively unchanged. Abdominal computed tomography (CT) scan: An abdominal CT scan with contrast can be used to identify enteric problems, such as bowel obstruction. It also is useful for imaging the liver and can demonstrate changes consistent with cirrhosis. Other earlier signs of liver dysfunction, such as fatty change, can be demonstrated as well. Abdominal ultrasonogram: Many patients with short-bowel syndrome develop biliary sludge or gallstones. Symptoms consistent with biliary colic or cholelithiasis can be investigated with abdominal ultrasonography. This study provides important information, such as indicating the presence or absence of stones, gall bladder wall thickness, and common bile duct diameter. Choledocholithiasis and fatty change of the liver may be demonstrated as well.

Other Tests

Bone densitometry o Patients with short-bowel syndrome, especially those on prolonged courses of total parenteral nutrition, can develop metabolic bone disease. The major mechanism is calcium and vitamin D malabsorption. Bone can become decalcified (less dense) and more prone to fracture. o Bone density is estimated by dual radiographic absorptiometry. Bone mineral density is measured in terms of g/cm2. The patient's bone density is measured and compared to reference values. A determination is made as to whether or not the patient is osteopenic. Patients deemed osteopenic could be treated with estrogen; calcitonin; bisphosphonates; or supplementation of calcium, vitamin D, and magnesium. Patients may be advised to increase their activity level as well.

Diagnostic Procedures

Liver biopsy: In patients with liver dysfunction that is suggested by biochemical or radiologic modalities, procurement of a tissue specimen may be advisable. Liver biopsies can be performed percutaneously under ultrasonographic or CT scan guidance.

Histologic Findings
Hepatic histology is most important in short-bowel syndrome. Many therapeutic decisions, including the decision to perform transplantation, are based on demonstrated alterations in liver histology. The type of transplant performed also depends upon the condition of the liver. Those patients with hepatic cirrhosis require a liversmall bowel transplant. Those without cirrhosis do well with an isolated intestinal transplant. Examples of diagnoses that can be made based on findings from histologic examination of liver biopsy specimens include cholestasis, fatty change, nonalcoholic steatohepatitis, and cirrhosis.

Features of intrahepatic cholestasis include bile plugs in dilated bile canaliculi. In fatty change, a large fat globule that crowds the nucleus to the cell periphery is observed in affected liver cells. Nonalcoholic steatohepatitis has elements of fatty change, with the addition of inflammatory cell infiltration and fibrotic changes. In hepatic cirrhosis, fibrotic material is deposited in large amounts in the area of the portal triads.

Medical Therapy
Patients undergoing massive small bowel resections frequently experience large fluid shifts and difficulties with volume and electrolyte homeostasis in the early postoperative period. The first priority is to ensure that the patient is adequately resuscitated and hemodynamically stable. Fluid and electrolyte disorders make up the most important group of complications in the early postoperative period in this group of patients, according to Cosnes and associates.[29] Scolapio and Fleming described therapeutic guidelines for the fluid and electrolyte management of these patients.[30] These include replacement of fluid and electrolytes lost through nasogastric suctioning and in stool. They recommended that 300-500 mL be added to the total volume administered to replace insensible losses. These replacement volumes are added to the patient's calculated daily maintenance volume. Daily urine output should be at least 1 L. Parenteral nutrition is an important therapy in the care of the patient with short-bowel syndrome. Parenteral nutrition provides adequate protein, calories, other macronutrients, and micronutrients until the bowel has had time to adapt. The time required for optimal bowel adaptation is a source of controversy. Booth stated that bowel adaptation may not be complete until a year or more after resection.[31] Carbonnel and others wrote that little bowel compensation occurs after 3 months.[32] Data from animal studies conducted by Wilmore and colleagues suggested that supplementing enteral intake with parenteral nutrition early in the postoperative course results in better overall bowel adaptation.[5] This is most likely because it facilitates provision of adequate calorie and nitrogen sources. According to Nightingale and colleagues, when enteral nutrient absorption falls to below one third of premorbid capacity, some amount of parenteral nutrition is needed.[33] Parenteral nutrition can be started with standard formulations and administered over the course of 24 hours daily on an inpatient basis. Make efforts to infuse daily requirements in shorter time periods before the patient is discharged. This is called cycling and it allows liberation from the solution pump for at least some time each day. In addition, laboratory studies, including serum chemistries and mineral and trace element levels, are monitored frequently and provision of these nutrients adjusted accordingly in the parenteral nutrition formula. Gradually, most patients are able to resume and increase oral food intake. This is begun by providing small frequent feedings and slowly advancing the diet as tolerated. According to Scolapio and Fleming, the process of weaning the patient off parenteral nutrition can begin once oral calorie intake exceeds 1000 kcal/d.[30] Further reductions in parenteral nutrition are predicated on increased oral intake. Woolf and associates reported that nutrient absorption is not complete in patients with loss of half or more of the small bowel.[34] Therefore, they usually require 30-40 kcal/kg/d to meet daily energy requirements.

A subset of patients who have lost significant amounts of ileum and colon may have massive fluid losses. Stomal outputs may exceed 2.5 L/d. Many of these patients are likely to be dependent on prolonged intravenous fluid therapy. Some may do well with oral sources of water, glucose, and sodium. Wilmore's group reported good success with the use of Gatorade.[21] Scolapio and Fleming stated that the solution should contain at least 90 mmol/L of sodium.[30] This may require supplementation with salt in some of the commercially available solutions. Despite bowel adaptation and meticulous nutritional therapy, some patients are unable to be liberated from parenteral nutrition. These patients usually are those with less than 60 cm of small bowel remaining, loss of the ileum and ileocecal valve, and loss of the colon. Wilmore, Byrne, and colleagues have been leaders in the concept of pharmacologic bowel compensation, which includes measures aimed at further enhancing bowel adaptation and increasing the chances that even these patients with difficult cases can be liberated from parenteral nutrition.[35] This includes provision of growth hormone 0.03-0.14 mg/kg/d subcutaneously for 4 weeks, parenteral (0.16 g/kg/d) or enteral (30 g/d) glutamine supplementation, and a high-carbohydrate diet with 55-60% of calories coming from carbohydrates versus 20-25% from fat and 20% from protein. Somatropin (Zorbtive) is a recombinant human growth hormone that elicits anabolic and anticatabolic influence on various cells, including myocytes, hepatocytes, adipocytes, lymphocytes, and hematopoietic cells. It exerts activity on specific cell receptors, including insulinlike growth factor-1 (IGF-1). Actions on the gut may be direct or mediated via IGF-1. Somatropin is indicated to treat short-bowel syndrome in conjunction with nutritional support. The adult dose is 0.1 mg/kg SC qd for up to 4 weeks (not to exceed 8 mg/d). Pediatric dosing has not been established. Teduglutide (Gattex), an analog of naturally occurring glucagon-like peptide-2 (GLP-2), was approved by the FDA in December 2012 for adults with short-bowel syndrome who are dependent on parenteral support. This agent binds to the GLP-2R receptors located in intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts, and enteric neurons of the submucosal and myenteric plexus. Activation of these receptors results in the local release of intestinal mediators that increases intestinal absorptive capacity, resulting in increased fluid and nutrient absorption. FDA approval was based on 2 clinical trials and 2 extension studies of patients randomly assigned to receive teduglutide or placebo. The studies were designed to measure the number of patients who achieved at least 20% reduction in the volume of weekly parenteral nutrition after 20 and 24 weeks of treatment. Patients treated with teduglutide achieved 46% and 63% clinical responses compared with 6% and 30% of patients treated with placebo.[90] A reduction in the volume of parenteral nutrition (liters per week) after 24 weeks of treatment was also observed. Results showed a mean reduction in parenteral nutrition of 2.5 L/week and 4.4 L/week in teduglutide-treated patients, compared with 0.9 L/week and 2.3 L/week in placebo-treated patients. Wilmore, Byrne, and colleagues published their results on 87 patients treated with this regimen in Current Problems in Surgery in 1997.[21] After 4 weeks, 52% were completely off parenteral nutrition and an additional 38% had significantly reduced parenteral nutrition requirements. The

same group of investigators published results with this regimen, also in 1997, in 45 patients with a jejunoileal remnant less than 50 cm and with a segment of colon remaining in continuity. After 4 weeks on the regimen, 58% were liberated from parenteral nutrition. After a mean follow-up of 1.8 years, this had fallen to 40%. Specific drug therapies in short-bowel syndrome are mainly aimed at decreasing gastric hypersecretion or decreasing diarrhea.[36, 37] Gastric hypersecretion may be treated by proton pump inhibitors or histamine-2 (H2) blockers in the early postoperative period. In most patients, gastric hypersecretion severe enough to cause clinical problems is self-limited. Diarrhea is a more vexing problem. When the patient is on nothing by mouth (NPO), codeine 60 mg IM q4h may be helpful. When enteral intake is resumed, Imodium (4-5 mg q6h) or Lomotil (2.5-5 mg qid) is useful. In refractory cases, tincture of opium in doses of 5-10 mL q4h may be tried. Cases involving patients who have lost all of their colon and ileum, with less than 100 cm of jejunum and an end jejunostomy, are the most difficult to manage. In these patients, the somatostatin analogue octreotide can be administered in doses of 100 mcg subcutaneously 3 times a day. This can reduce stool output by as much as 50% according to Farthing.[38]

Surgical Therapy
Operative therapies for short-bowel syndrome can be divided into 2 broad categories: (1) intestinal or combined liver-intestinal transplantation, and (2) nontransplant operations. Nontransplant components of the surgical armamentarium for the treatment of short-bowel syndrome include intestinal lengthening (Bianchi) procedures, intestinal tapering for dilated dysfunctional bowel segments, strictureplasty, and creation of intestinal valves or reversed bowel segments for patients with rapid intestinal transit times. In 1995, Thompson et al reported their results from various nontransplant and transplant surgical procedures in 160 patients with short-bowel syndrome.[39] The study population included 48 adults and 112 children. In this population, the type of operation was selected based on criteria that included the age of the patient; the remaining bowel length; the presence or absence of bowel dilatation; the overall functional status of the bowel remnant, including intestinal transit time; and the presence or absence of complications related to parenteral nutrition. Fifteen patients had intestinal remnants greater than 120 cm but with dilated dysfunctional bowel, in some cases proximal to a stricture. Patients in this group underwent Heineke-Mikulicz strictureplasties (n = 4) or intestinal tapering procedures (n = 11). Intestinal tapering creates a decrease in the circumference of dilated bowel by imbrications or resections of a portion of the antimesenteric side of the intestine. Approximately 87% of these 15 patients experienced clinical improvement. Small bowel remnants 90-120 cm associated with rapid intestinal transit times were present in 14 patients. Two of these patients underwent creation of an artificial valve, which is made by intussuscepting a distal small bowel segment and suturing it in place. Both of these patients improved clinically. A reversed segment was placed in one patient but subsequently was taken down because of poor bowel function.

Intestinal lengthening was performed in 14 patients who had short small bowel remnants that were dilated. Intestinal lengthening is performed by transecting the bowel segment along its longitudinal axis between the antimesenteric and mesenteric borders. This converts one dilated loop of intestine into 2 parallel segments that then are anastomosed in series. Clinical improvement was observed in 86% of these patients. In 1997, Thompson and Langnas reported additional results from nontransplant operations for treatment of short-bowel syndrome.[40] Ninety patients were evaluated for possible surgical therapy. Thirty-seven of 43 procedures (86%) resulted in clinical improvement. The best results were achieved with operations designed to increase intestinal surface area, such as restoration of gastrointestinal tract continuity and intestinal lengthening (86%), and those that were intended to correct functional problems, such as strictureplasty, the removal of diseased bowel segments, and closure of fistulae (85%). Clinical improvement rates of only 50% were observed in patients who underwent operations aimed at slowing intestinal transit time, such as creation of valves or reversed segments. In contrast, Panis reported good results in patients treated with segmental small bowel reversal.[41] However, his series was small (n = 8). These patients had very short small bowel remnants (median was 40 cm). The median length of the reversed segment was 12 cm. Median follow-up was 35 months. One patient died of a pulmonary embolism in the seventh postoperative month. Of the remaining 7 patients, 3 were completely liberated from parenteral nutrition, 1 required only intravenous fluid and electrolyte therapy, and 3 received only 3-5 nocturnal cycles of parenteral nutrition per week. Javid and colleagues published their results with serial transverse enteroplasty (STEP) for the treatment of short-bowel syndrome in infants.[42] A total of 5 children underwent this intestinal lengthening procedure. No significant perioperative complications were reported. The percentage of protein-energy nutrition that the patients were able to take enterally increased significantly in this group following STEP (p < 0.05). One child was able to be completely liberated from parenteral nutrition and another child's severe cholestasis was reversed. Oliveira et al examined 5-year outcomes after STEP in 12 children (median age 5.5 months) with short bowel syndrome. Of these 12 patients, 2 underwent liver-intestinal transplants and 2 died of liver failure, while the other 8 all exhibited stable intestinal absorptive capacity at follow-up. Among these 8 patients, 7 were weaned off parenteral nutrition by age four. Repeat STEP or bowel tapering was not necessary in any of the patients.[43] Organ transplantation is a recent addition to the surgical approach to short-bowel syndrome. From the outset, intestinal transplantation faced many hurdles, first and foremost because of the massive amount of lymphoid and immunologic tissue associated with the gastrointestinal tract. Effective immunosuppressant drugs needed to be developed. Techniques and postoperative care needed to be refined, and the actual indications for transplantation needed to be clarified. Worldwide, an estimated 25-30 centers are actively engaged in intestinal or liver-intestinal transplantation procedures for short-bowel syndrome.

In 1995, Todo, Reyes, and colleagues reported their experience with 71 isolated intestinal (n = 22), liver-intestinal (n = 30), and multiorgan (n = 11) transplants in 66 patients performed from 1990-1995 at the University of Pittsburgh Medical Center.[44] At the time of the report, just over 50% of the patients were alive. Thirty-five grafts had been lost. Sepsis (n = 19) was the most common cause of graft loss, followed by management errors (n = 10) and rejection (n = 6). The authors performed linear regression analysis to identify factors correlated with graft loss. They identified prolonged operative time, inclusion of colon in the graft, a positive cytomegalovirus (CMV) donor infection status, high tacrolimus (FK506) blood levels, use of OKT3, and steroid recycling as predictors of graft loss. During the course of this study, 4 patients received combined intestinalbone marrow transplants. They were all doing well at 2-3 months of followup. Langnas et al described their experience at the University of Nebraska with 13 liver-intestinal transplants and 3 isolated intestinal transplants in infants and children.[45] Their results were published in 1996. In children who received combined liver-intestinal grafts, the 1-year actuarial patient survival rate was 76% and the 1-year actuarial graft survival rate was 61%. Six of these patients had been liberated from parenteral nutrition. All 3 who received isolated intestinal grafts were alive and free from parenteral nutrition. Most significant complications in this series were related to sepsis and graft rejection. In 1998, Abu-Elmagd et al updated the University of Pittsburgh experience with liver-intestinal and isolated intestinal transplantation.[46] Their results in 59 adults and 39 children were presented. These patients received either liver-intestinal (n = 50), isolated intestinal (n = 37), or multivisceral (n = 17) grafts. Twenty were augmented with donor bone marrow. Tacrolimus was the primary immunosuppressant used in all cases. With a mean follow-up duration of 32 months, 48% of patients were alive with grafts that allowed complete (91%) or partial (9%) liberation from specialized nutritional support. In addition, 12 patients had passed the 5-year milestone. The actuarial patient survival rates at 1 and 5 years were 72% and 48%, respectively. Bone marrow transplantation did not appear to increase graft survival. In 2007, Sudan et al published their clinical results of intestinal lengthening procedures.[47] An outcome analysis of a longitudinal intestinal lengthening (Bianchi procedure) and a serial transverse enteroplasty (STEP procedure) was done. Fifty pediatric patients and 14 adult patients were included in the study. All patients had dilated small bowel loops greater than 3.9 cm in size and also had poor enteral progression.[47] The patients underwent 43 Bianchi procedures and 34 STEP procedures. The average intestinal length increased from 44 cm to 68 cm for the Bianchi procedure and from 45 cm to 65 cm for the STEP procedure. One year after the lengthening procedures, 69% of the patients were off total parenteral nutrition. The authors of this study concluded that surgical lengthening procedures result in an improvement in enteral nutrition.[47]

Preoperative Details
Patient selection is paramount to operative success. Tailor nontransplant operative approaches to the patient's remaining length of intestine, the presence or absence of strictures or areas of stasis, bowel dilatation, and the intestinal transit time as described above. Various radiographic techniques, including contrast small bowel follow-through and CT scanning, are helpful in the decision. Transplant surgery is usually reserved for patients who are dependent on parenteral nutrition, who have run out of venous access, who have had several episodes of central linerelated sepsis, or who have begun to manifest progressive parenteral nutritionassociated liver dysfunction. Identify these patients early and perform transplant prior to the development of hepatic cirrhosis. This may obviate the need to perform a combined liver-intestinal transplantation, and results are better in patients who have not yet developed cirrhosis, according to Vanderhoff and Langnas.[22] According to Abu-Elmagd and colleagues, grafts in their series were obtained from blood group (ABO) antigen-matched cadaveric donors.[48] Although human leukocyte antigen (HLA) matching was performed, it usually was poor, and 13 patients in their series had lymphocytotoxic positive cross-matches.

Intraoperative Details
Although a full dissertation on the operative technique is beyond the scope of this discussion, the authors outline the procedures of combined liversmall bowel transplantation and isolated small bowel transplantation (see Relevant Anatomy and Indications). Some details that bear discussion here were published by Abu-Elmagd and colleagues.[48, 46] The University of Wisconsin solution was used for graft preservation. These investigators have preserved the donor enteric and celiac ganglia as a measure to decrease postoperative graft dysmotility. Nontransplant operations require meticulous technique as well. The bowel must be handled gently and the blood supply guarded jealously. Abdominal visceral organ procurement may begin with an attempt at gastrointestinal tract sterilization by intragastric administration of a nonabsorbable antibiotic suspended in a cathartic solution. Proximal and distal abdominal aortic control is achieved at the aortic hiatus and caudal to the inferior mesenteric artery. The proximal aorta is clamped, and the distal aorta is cannulated. Cold preservation solution is used to perfuse the abdominal viscera to be excised and transplanted. Drainage is provided by the creation of a venotomy in the suprahepatic inferior vena cava. The bowel is stapled proximally and distally. Other visceral vascular connections are divided and the graft specimen removed. If the patient is to receive a transplant consisting of the liver and intestine, gastrointestinal tract continuity is restored by proximal and distal anastomosis. Some authors have advised creation of proximal and distal stomas via limbs of intestine because prolonged intestinal decompression may be necessary in the early postoperative period. Arterial blood supply is reestablished by anastomosis of a Carrel patch of the celiac axis and superior mesenteric artery to the aorta, or, if

donor aorta is included, an aorto-aortic anastomosis is possible. Venous drainage of the intestine is intact to the liver in a combined hepatic-intestinal transplant. Hepatic venous drainage can be accomplished by harvesting donor retrohepatic inferior vena cava with preservation of the donor hepatic veins distally. This is anastomosed to the recipient inferior vena cava circumferentially. Alternately, the donor inferior vena cava can be anastomosed to the recipient vena cava via an anterior venotomy. This anastomosis "piggybacks" the hepatic venous outflow onto the anterior surface of the recipient vena cava. This requires ligation of the caudal aspect of the donor inferior vena cava. Venous outflow for the recipient's retained organs, such as the stomach, pancreas, and duodenum, can be established by anastomosis of the recipient portal vein to the donor vena cava or the donor portal vein. When isolated intestinal grafts are used, a Carrel patch of the donor superior mesenteric artery is anastomosed to the recipient aorta. A long segment of donor superior mesenteric and portal vein is preserved for anastomosis to the recipient portal vein. Gastrointestinal tract continuity is reestablished as described above.

Postoperative Details
Postoperatively, fluid and electrolyte balance must be assured. Some of these guidelines have been discussed under the Medical Therapy section above. Calculated maintenance fluids are administered, and nasogastric, stool, stoma, and fistula outputs are recorded. These are replaced with fluids of similar makeup. Most frequently, this involves lactated Ringer solution. If large amounts of gastric secretions are lost, isotonic sodium chloride solution might be a more appropriate choice. Most patients are maintained on parenteral nutrition initially. Enteral intake should be started as soon as possible, beginning with small amounts and gradually increasing. Several smaller feedings per day are usually advisable. Transplant recipients are begun on immunosuppressive drug therapy. Standard immunosuppression regimens are based on tacrolimus and prednisone. Investigators at the University of Pittsburgh have used adjunctive drugs, such as cyclophosphamide, mycophenolate mofetil, and azathioprine, early in the postoperative period as well.

Follow-up
Patients with short-bowel syndrome require lifetime follow-up. Those on parenteral nutrition require frequent monitoring of serum chemistries; liver function tests; and vitamin, mineral, and trace element levels.[49] Patients should be weighed regularly following resolution of postoperative fluid flux to assure that they are not losing weight on the nutritional regimen they are receiving. Nitrogen balance studies can be performed but are cumbersome because of the need for 12- to 24-hour urine collection. Patients receiving specialized enteral nutrition can be monitored with similar measures.

Patients who have had nontransplant operations are monitored to assure that proper wound healing and bowel function are occurring. In addition, several of the measures described above can be applied to their postoperative care. Ascertaining that they can ingest and absorb adequate amounts of protein and calories is important. Patients who receive single or multiple organ transplants are monitored, and their cases are followed closely. The most dreaded postoperative complications that must be identified early include organ rejection, opportunistic infection, and development of immunosuppression-related malignancies. These patients may be monitored by all the measures mentioned above. In addition, immunosuppressant drug levels can be monitored. The physician usually diagnoses acute rejection by endoscopically guided mucosal biopsies, and chronic rejection is diagnosed definitively by complete examination of resected grafts. Transplant patients must also be monitored for evidence of graft versus host disease. Typically affected areas include the skin, gastrointestinal tract, liver, and lungs.

Complications
Both nontransplant and transplant patients can experience the typical postoperative complications of surgical patients in general. These include hemorrhage, wound complications, postoperative pulmonary dysfunction, renal failure, and pulmonary embolism, to name a few. In nontransplant patients, the following postoperative complications may occur:

Bowel obstruction Bowel necrosis Bowel dysmotility and dysfunction Anastomotic disruption Stasis of intestinal contents with or without bacterial overgrowth

Transplant recipients are subject to all the complications mentioned above. In addition, they may develop serious and sometimes lethal complications specifically related to transplantation and immunosuppression, such as the following:

Acute rejection Chronic rejection Hepatic, portal, or mesenteric vein thrombosis Systemic sepsis with ordinary pathogens or opportunistic organisms (eg, CMV) Lymphoproliferative disorders or malignancies

Outcome and Prognosis

No reliable cure currently exists for short-bowel syndrome. Patients who are maintained on parenteral nutrition at home have reasonably good short-term outcomes. Data from Howard and colleagues and Ladefoged and coworkers revealed that the 4-year survival rate in patients who

depend on parenteral nutrition is about 70%.[11, 50] Eventually, many of these patients run out of venous access or have severe septic complications. Cost also is a major factor. Home parenteral nutrition costs range from about $50,000 to more than $200,000 per year. As mentioned before, the most common cause of death in these patients is liver failure. The authors have reviewed the use and results of pharmacologic bowel compensation, including growth hormone, glutamine, and a high-carbohydrate diet. This may allow additional patients to be liberated from parenteral nutrition. The clinical results have been favorable as described in the studies by Wilmore, Byrne, and colleagues, but these results have not been reproduced at numerous medical centers.[21] Nontransplant surgical procedures have been applied to short-bowel syndrome. Early results were mixed, but many of the procedures being performed then involved segment reversal. The most recent series described herein have demonstrated clinical improvement in greater than 80% of patients. The most common operations performed in these series were intestinal tapering, intestinal lengthening, and strictureplasty. Even in these series, segment reversal and creation of artificial valves produced dubious results. Organ transplantation is a promising therapeutic option but continues to be fraught with problems. Early postoperative mortality rates can be as high as 30%. Data from leading transplant centers have shown that the 1-year survival rates can be as high as 80-90%, and approximately 60% of patients are alive at 4 years.

Future and Controversies

Future developments in the therapy of short-bowel syndrome will consist of finding ways to maximize bowel adaptation and of refining techniques of transplantation and immune modulation. Pharmacologic bowel compensation is a novel idea and has had some good results to date. Better understanding of small bowel trophic signals and the interaction among foodstuffs, enteric hormones, and the intestinal mucosa might lead to improved bowel adaptation. Transplantation techniques are improving, and factors that negatively impact the success of these operations have been described and discussed. The introduction of tacrolimus was associated with increasing 1-year graft survival rates from 19-57%. Problems still exist. Rates of sepsis and immunosuppression-related malignancies are still high. The search for the transplantation "holy grail" of donor-specific immunologic tolerance continues. Animal studies by Gorczynski and others have suggested that introduction of donor antigens via the portal vein before implantation might help induce a state of tolerance.[51] So far, this has not been demonstrated in humans. The identification of the gamma-delta receptorpositive T (GDT) cell was an exciting discovery. GDT cells are a source of type 2 cytokines, including interleukin (IL)-4, IL-10, and transforming

growth factor (TGF) beta. These type 2 cytokines are associated with enhanced graft survival, making the GDT cell an intense research topic.