AGA technical review on short bowel syndrome and intestinal transplantation☆☆☆★★★♢♢♢

Article Outline

• Abstract
• Methods
• Incidence and prevalence of short bowel syndrome
• Pathophysiology of short bowel syndrome
• How does the remaining intestine adapt following resection?
  • Effects of massive enterectomy on gastrointestinal motility and transit time
• Medical therapy of short bowel syndrome
  • Macronutrient assimilation and dietary therapy
    • Proteins and amino acids
    • Lipid
    • Carbohydrates
    • The role of soluble fiber
    • Vitamins
    • Trace metals
  • Medication absorption
  • Fluid and electrolyte management
  • Pharmacologic enhancement of intestinal adaptation
  • Dietary restriction
  • Providing parenteral nutrition
    • Macronutrients
  • Getting the patient ready for home TPN
  • Quality of life and survival of short bowel patients
  • Complications of long-term TPN
    • Hepatic complications
    • Biliary complications
    • Catheter-related infections
    • D-lactic acidosis
    • Catheter occlusion
    • Other complications
• Role of surgery
  • Nontransplant surgery
  • Intestinal transplantation
    • Indications for transplantation
    • Outcomes of patients waiting for intestine transplants
  • Outcomes of patients undergoing intestinal transplantation
    • The world experience
    • Patient and graft survival
  • Posttransplant complications
  • Quality of life in home TPN patients and intestinal transplant recipients
  • Financial concerns of home parenteral nutrition and intestinal transplantation
• References
• Copyright

Abstract 

This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice Committee. This paper was approved by the Committee on August 5, 2002, and by the AGA Governing Board on November 1, 2002.

Abbreviations:  CMV , cytomegalovirus, CTP , Child-Turcotte-Pugh, CVC , central venous catheter, ESLD , end-stage liver disease, GLP-I , glucagon-like peptide I, ITR , Intestinal Transplant Registry, IVC , inferior venous catheter, LCT , long-chain triglyceride, LILT , longitudinal intestinal lengthening and tailoring, MCT , medium-chain triglyceride, ORS , oral rehydration solution, SBS , short bowel syndrome, SCFA , short-chain fatty acid, SRSB , segmental reversed small bowel, SVC , superior venous catheter, UNOS , United Network of Organ Sharing

This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice Committee. This paper was approved by the Committee on August 5, 2002, and by the AGA Governing Board on November 1, 2002.

The normal human small intestine length is generally considered to be between 3 and 8 meters, depending upon whether radiologic, surgical, or autopsy measurements are made.¹, ², ³, ⁴, ⁵ Short bowel syndrome (SBS) occurs when there is <200 cm of bowel remaining. This is an approximate length as most methods of residual intestine measurement (such as radiologic contrast studies, pathology of the resected specimen, and perioperative measurement of unweighted intestine) are not especially accurate. Because absorption is related to the amount of residual intestine, it is more important to document the amount of remaining, viable intestine.

Those patients at greatest nutritional risk generally have a duodenostomy or a jejunoileal anastomosis with <35 cm of residual small intestine, jejunocolic or ileocoloic anastomosis with <60 cm of residual small intestine, or an end jejunostomy with <115 cm of residual small intestine.⁶, ⁷, ⁸ It has been suggested that intestinal failure is better defined in terms of fecal energy loss rather than residual bowel length.⁹ Given the observations that fecal energy loss does not always correlate well with residual bowel length,⁹ and the significant individual variability in jejunal absorption efficiency,¹⁰ it is reasonable to consider a more standardized approach to defining intestinal failure and “functional” SBS from a clinical standpoint. However, fecal energy loss is a function of both energy intake and energy absorption. Patients who are unable to increase their oral intake sufficiently or are unable to absorb sufficient energy despite significantly increased intake, are defined as patients with intestinal failure and require parenteral nutrition support. A standardized diet may be useful for clinically defining functional SBS, although there is insufficient data with regard to what the composition of such a diet optimally should be.

Back to Article Outline

Methods 

Most available data on the treatment of SBS are based on retrospective analyses of case series (type II-3 or type III data) and are often few in number, because of the rareness of the covered diseases, where randomized, controlled trials were undertaken (type 1 and type IIb data), and the studies are described in detail. Data and reports were obtained from extensive PubMed and Medline searches using several key words, including SBS, various conditions predisposing to SBS, parenteral nutrition, enteral nutrition, relevant specific nutritional deficiencies, intestinal surgery, and intestinal transplantation. In addition, surgical and gastroenterological texts, published national and international scientific meeting abstracts, and the extensive manuscript/abstract files of the authors were reviewed. Expert opinion was sought for the few areas in which no suitable published reports existed (e.g., TPN cycling and preparation of the patient for home TPN). Human data and reports were reviewed exclusively.

Patients with functional SBS who have severe malabsorptive processes related to refractory sprue, chronic intestinal pseudo-obstruction syndrome, or congenital villus hypoplasia are not the specific focus of this technical review, although most of the medical and nutritional management problems and therapies are similar, if not identical.

Back to Article Outline

Incidence and prevalence of short bowel syndrome 

It is unclear how many individuals in the USA suffer from SBS, but based on the numbers in Europe, the incidence may be ≅2 per million.¹¹ More recent data from 1993 indicated the incidence and prevalence of home parenteral nutrition, for which SBS was the most prevalent indication, increased slightly to 2-3 per year per million inhabitants and 4 per year per million, respectively.¹², ¹³ The most recent European survey, in 1997, indicated the incidence of home TPN increased slightly to ≅3 per million and the prevalence had increased to 4 per million.¹⁴ SBS constituted the largest single group of patients who required home TPN (35%). In comparison, the most recent data for incidence and prevalence in the USA is from 1992. At that time, it was estimated based on extrapolated data from the Oley Foundation Home TPN Registry that ≅40,000 patients required TPN each year.¹⁵ Approximately 26% of the patients in the Oley registry had SBS, although some patients with a primary TPN indication of malignancy or radiation enteritis may have had SBS as well. These numbers for either Europe or the USA do not reflect patients with SBS who never required TPN or for whom TPN could be discontinued successfully. Approximately 50%-70% of the short bowel patients who initially require TPN can be weaned off TPN successfully in optimal settings with better outcomes in children.⁶, ¹⁶ Therefore, the number of patients with SBS may be substantially greater than previously estimated. A registry of short bowel patients, including those who require TPN permanently, transiently, and not at all, should be implemented.

Back to Article Outline

Pathophysiology of short bowel syndrome 

SBS may be a congenital or acquired condition. Infants born with intestinal atresia (jejunal or ileal) constitute the congenital forms. Otherwise, SBS results from surgical resection of bowel. This is usually related to multiple resections for recurrent Crohn's disease, massive enterectomy made necessary because of a catastrophic vascular event (such as a mesenteric arterial embolism or venous thrombosis, volvulus, trauma, or tumor resection in adults, and in children, gastroschisis, necrotizing enterocolitis), intestinal atresias, and extensive aganglionosis. Functional SBS may also occur in cases of severe malabsorption where the bowel length is often intact. Such conditions may include chronic intestinal pseudo-obstruction syndrome, refractory sprue, radiation enteritis, or congenital villus atrophy. Severe nutrient and fluid malabsorption occurs following extensive small intestinal resection. Patients with <100 cm of jejunum remaining generally have a net secretory response to food.¹⁷

Patients can be grouped into 2 distinct subgroups: those with intact colon in continuity and those without colon in continuity. In patients with SBS, the colon becomes an important digestive organ. The colon absorbs sodium, water, and energy from short-chain fatty acids (SCFAs) (see below discussion regarding soluble dietary fiber).⁸, ¹⁸, ¹⁹

Back to Article Outline

How does the remaining intestine adapt following resection? 

Patients often clinically adapt to the significantly reduced energy absorption associated with SBS through hyperphagia. However, the intestine adapts as well to ensure more efficient absorption per unit length. After massive enterectomy, the intestine hypertrophies and becomes more efficient in nutrient absorption; there is slight lengthening, but more importantly, diameter and villus height increase, effectively increasing the absorptive surface.²⁰, ²¹, ²², ²³ This process may evolve over 1 or 2 years.⁶, ⁸, ²⁴ Several factors are important determinants in the functional adaptation process and clinical outcome.⁶, ²⁵, ²⁶ These include the presence or absence of the colon and ileocecal valve, length of remaining bowel, health of the remaining bowel, patient age, and comorbid conditions. Although the length of remaining bowel necessary to prevent dependence on TPN is ≅100 cm in the absence of an intact and functional colon or 60 cm in the presence of a completely functional colon,⁶, ⁸ the degree of adaptation and TPN dependence may be highly individualized. In infants, adaptation to full enteral nutrition has been reported with as little as 10 cm of residual intestine.²⁴ However, Carbonnel et al. found small bowel length, determined radiographically, to be an independent risk factor for loss of nutritional autonomy in 103 patients, of which 24 became TPN dependent.⁷ In addition, those with a jejunostomy were at increased risk for TPN dependence and those with a jejunal-ileal anastomosis were at decreased risk. Patients with active Crohn's disease, radiation enteritis, carcinoma, or pseudo-obstruction involving their remaining bowel will have a blunted adaptation response.

Animal models of SBS have suggested several gut hormones are involved in postresection intestinal adaptation. These include enteroglucagon, glucagon peptide II, epidermal growth factor, growth hormone, cholecystokinin, gastrin, insulin, and neurotensin.²⁷ There is little data on the role of either endogenous or exogenous hormones on intestinal adaptation in humans.

Despite the fact that, normally, most nutrients are absorbed in the proximal jejunum, the residual ileum is able to adapt and to assume the role of macronutrient absorption. However, the specialized cells of the terminal ileum, where vitamin B₁₂ /intrinsic factor receptors are located and where bile salts are reabsorbed, cannot be replaced by jejunal hypertrophy.

Effects of massive enterectomy on gastrointestinal motility and transit time 

Following small intestinal resection, dysmotility may develop, which may predispose to bacterial overgrowth in the residual intestine. In addition, resection of the ileocecal valve allows colonic bacteria to enter and populate the small intestine.²⁸ Bacterial overgrowth may negatively impact on digestion and nutrient assimilation, as bacteria compete for nutrients with the enterocytes. Diagnosis may be more difficult using breath tests because of more rapid intestinal transit in short bowel patients. Endoscopically obtained small bowel aspirate for culture may be required. Treatment can be undertaken with oral metronidazole, tetracycline, or other antibiotics.

Following jejunal resection, gastric emptying of liquids is more rapid, although intestinal transit may still remain normal because of the braking effect of the ileum.²⁹ Gastric emptying is significantly slower in patients who have residual colon in continuity and is similar to normal controls. The loss of inhibition on gastric emptying and intestinal transit in patients without colon is related to a significant decrease in peptide YY (PYY), glucagon-like peptide I (GLP-I), and neurotensin.³⁰ PYY is normally released from L cells in the ileum and colon when stimulated by fat or bile salts. Obviously, these cells are missing in patients who had distal ileal and colonic resection. Those patients with the shortest residual jejunum (<100 cm residual) exhibit the most rapid liquid gastric emptying.²⁹ Solid emptying may also be more rapid in these patients. Rapid gastric emptying may contribute to fluid losses in patients with SBS.

Back to Article Outline

Medical therapy of short bowel syndrome 

The goal of medical therapy is for the patient to resume work and a normal lifestyle, or as normal of one as possible. This is undertaken via the use of specific measures to gradually decrease the requirement for TPN, and at best, to eliminate its need. The most important aspects of the medical management of the patient with SBS are to provide adequate nutrition, including both macro- and micronutrients (to prevent energy malnutrition and specific nutrient deficiencies), to provide sufficient fluid (to prevent dehydration), and to correct and prevent acid-based disturbances. Most macronutrients, including carbohydrate, nitrogen, and fat, are absorbed within the first 100 cm, and up to 150 cm of jejunum.³¹

Macronutrient assimilation and dietary therapy 

Typically, patients who have undergone massive enterectomy require TPN for the first 7-10 days. Nutritional therapy should not be introduced until the patient is hemodynamically stable and fluid management issues are relatively stable. The goal is to provide patients with ≅25-35 kcal/kg per day depending upon whether nutritional support is for maintenence or correction of undernutrition and 1.0-1.5 kg per day of protein (Table 1).

Table 1. Dietary Macronutrient Recommendations for Short Bowel Syndrome

LCT, long-chain triglyceride; MCT, medium-chain triglyceride.

Additional energy and protein are required by children, especially infants and neonates. Some debate exists whether the patient's actual body weight or ideal body weight should be used in this calculation. For the postoperative patient, standard enteral formula is recommended. These should be instituted gradually as tolerated. Once patients are able to eat, they should be encouraged to eat a regular diet, but modified as described below. There is no value in separating liquids from solids in the diet. Such practices have no effect on macronutrient, electrolyte or mineral absorption, fecal volume, or fecal weight.¹⁸

Proteins and amino acids 

Dietary protein is first digested, and then absorbed as dipeptides and tripeptides. Therefore, it was reasoned that dietary protein provided in a predigested form would be more readily absorbed. However, nitrogen absorption is the macronutrient least affected by the decreased intestinal absorptive surface. Therefore, the utility of peptide-based diets in such patients is generally without merit. McIntyre et al. compared energy, nitrogen, and fat absorption, as well as stool weight in 7 patients, all with end-jejunostomy and <150 cm (range, 60-150 cm) of remaining small intestine. These patients were fed with either a peptide-based or an essentially isocaloric and isonitrogenous polymeric formula. Although the study was small, no differences were observed in energy, nitrogen, fat, carbohydrate, electrolyte, mineral, or fluid absorption.³² Uncontrolled data from Levy et al. supports these findings.³³ However, in a small study of 6 patients, all with 90-150 cm of residual jejunum and end-jejunostomy, data from Cosnes et al. suggests nitrogen absorption may be improved with the use of a peptide-based diet. Energy, other macronutrient, electrolyte, mineral, and fluid absorption was unaffected.³⁴ Therefore, the clinical effect of the modestly increased nitrogen absorption was insignificant. It must be recognized that all the studies described above were very small, the study populations somewhat heterogeneous, the various peptide constituents and their concentrations in these various formulas differed significantly, and there was variation in the type and amount of fat (long-chain triglycerides [LCTs] versus medium-chain triglycerides [MCTs]). It is therefore difficult to make definitive comparisons between studies.

The amino acid glutamine, together with glucose, is the preferred fuel for the small intestinal enterocyte.³⁵ Rodent TPN models suggested that both parenteral or enteral glutamine supplements could effect more rapid and significant bowel adaptation following massive enterectomy.³⁶, ³⁷ Therefore, it was thought glutamine supplementation in humans would have a similar effect. Although an early case series of 10 patients suggested that glutamine, combined with growth hormone supplementation and a high complex carbohydrate diet could result in decreased stool output and increased absorption of energy, protein, carbohydrate, sodium, and water,³⁸ 2 subsequent double-blinded, randomized placebo-controlled trials failed to confirm any of these effects.³⁹, ⁴⁰ In addition, Scolapio et al. showed that glutamine and growth hormone supplementation did not lead to morphological changes in the intestine.³⁹ Glutamine-supplemented oral rehydration solution (ORS) (see fluid and electrolyte management) was associated with decreased Na absorption and a trend toward decreased fluid absorption in a small controlled trial in 6 patients.⁴⁰, ⁴¹ All of the patients studied by Byrne et al. had colon in continuity³⁸; it is likely the treatment-associated increase in energy absorption was related solely to the increased complex carbohydrate diet discussed above. Treatment with growth hormone and glutamine in the setting of SBS has been associated with significantly increased extracellular fluid and peripheral edema.³⁹, ⁴², ⁴³ Therefore, treatment with glutamine and growth hormone cannot be recommended.

Lipid 

Luminal digestion of lipid may be impaired because of impaired bile salt reabsorption related to resected ileum (>100 cm).⁴⁴ Therefore, treatment with ox bile supplements has been attempted in 3 cases to increase the duodenal bile salt concentration to a concentration greater than the level at which micellar solubilization of lipid occurs.⁴⁵, ⁴⁶, ⁴⁷ Unfortunately, this therapy has been associated with significantly increased fecal volume, at least in those patients with intact colon. A preliminary, open-labeled study of 4 patients (2 with colon in continuity) indicated treatment with the conjugated bile acid cholylsarcosine (6 g/day) was associated with an increase in fat absorption of 17 ± 3 g/day without any effect on stool wet weight.⁴⁸ As a conjugated bile acid, cholylsarcosine is resistant to colonic bacterial deconjugation, although 1 of the 4 patients did experience a significant increase in wet stool output and another experienced nausea. Cholestyramine is not useful in patients with >100 cm of ileal resection, and may actually worsen steatorrhea because of the binding of dietary lipid.⁴⁹

Although dietary fat restriction may result in increased fecal fat losses, there is no difference in the percentage of fat absorbed between high fat (75% nonprotein calories derived from fat)/low carbohydrate and low fat/high carbohydrate, isocaloric and isonitrogenous diets.⁵⁰ In addition, stool weight did not differ between diets. Because fat is energy-dense (9.0 kcal/g) when compared to carbohydrate (4.0 kcal/g), fat restriction may ultimately deprive the patient of a necessary source of energy. Up to 65% of dietary carbohydrate may be malabsorbed and lost in the feces without degradation by colonic bacteria.³¹

The colon also absorbs MCTs (C8-C10), possibly related to the fact that MCTs are water soluble. In a study of 10 short bowel patients with colon in continuity and 9 patients with no residual colon, [randomized in a cross-over design to consume an LCT diet based on ordinary dietary fat, consisting of 20% carbohydrate, 24% protein, and 56% fat versus an MCT-LCT diet, where 50% of the LCT was replaced with MCT (margarine, MCT oil)],⁵¹ those patients with intact colon absorbed 96% ± 3% of C8 and 87% ± 6% of C10, versus 63% ± 25% for C8 and 57% ± 28% for C10, respectively, in patients with no residual colon (P = 0.007 for C8 and P = 0.004 for C10) from the mixed LCT-MCT diet. Significantly increased energy absorption (≅2.1 MJ/day; 500 kcal/day) was found in patients with colon, but the LCT-MCT diet did not result in increased energy absorption when compared to the LCT diet in patients with an end-jejunostomy or ileostomy whose fecal output was also increased. MCT contain 8.3 kcal/g. Some, but not all, LCT can be replaced by MCT in the diet. In a short bowel patient eating 10.5 MJ/day (2500 kcal/day), ≅1.5-3 MJ/day (360-720 kcal/day; 40-80 g) of LCT can be replaced with MCT. However, LCTs are still necessary to provide essential fatty acids, and primarily linoleic fatty acid, which is not found in MCTs. In addition, excessive intake of MCT may result in nausea, vomiting, and ketosis.

Carbohydrates 

Rarely is the proximal jejunum resected in patients who require massive enterectomy. Because most intestinal disaccharidases are present in highest concentration proximally, it would stand to reason such patients would be unlikely to benefit from a lactose-free diet. Marteau et al. studied 14 short bowel patients in whom a lactose-free diet was compared to a diet containing 20 g/day containing ≤4 g milk.⁵² Lactose absorption, breath hydrogen, subjective symptoms of flatulence, and diarrhea were similar regardless of which diet was consumed. This data confirmed the findings of an earlier controlled study in 17 short bowel patients where it was also reported that lactose absorption was enhanced when provided in yogurt rather than via milk.⁵³ Regardless, in the absence of significant jejunal resection, lactose should not be restricted in the diet of the short bowel patient. The amount of lactose found in a glass of milk (20-25 g) is generally well tolerated even in patients with an end-jejunostomy.⁵³ Because most lactose is found in milk-based foodstuff, which are also the most important source of dietary calcium, dietary lactose restriction will result in insufficient dietary calcium intake.

The role of soluble fiber 

Soluble nonstarch polysaccharides and some starches⁵⁴ are not generally absorbed by the small intestine. Soluble fiber is water soluble and found primarily in the following (in descending order of concentration): oatmeal, oat bran, psyllium (Metamucil, Procter and Gamble, Cincinnati, OH; Konsyl, Konsyl Pharmaceuticals, Ft. Worth, TX), barley, artichokes, strawberries, legumes, prunes, grapefruit, and squash. Soluble fiber and starches pass undigested into the colon where colonic bacteria ferment them not only to hydrogen and methane, hence patient “gas” complaints, but also to SCFAs, including butyrate, proprionate, and acetate. SCFAs are the preferred fuel for the colonocyte.⁵⁵ Therefore, in the patient with SBS, the colon becomes an important machine for energy absorption. Approximately 75 mmol of SCFA are produced from 10 g of unabsorbed carbohydrate.⁵⁶ Patients with SBS, but intact colon in continuity were able to decrease fecal energy loss by 1.3-3.1 MJ/day (310-740 kcal) when they were fed a diet consisting of 60% carbohydrates.⁵⁷ Colonic metabolism of unabsorbed carbohydrate was indicated by decreased fecal carbohydrate losses in the patients with colon in continuity. It is possible for an intact colon to absorb up to 2.2-4.9 MJ (525-1170 kcal) daily from dietary fiber.⁸, ⁹, ⁵⁷ Colonic energy absorption may also increase somewhat during the postresection adaptation phase, related to increased colonic bacterial carbohydrate fermentation.¹⁰, ⁵⁸ This may be related to increased colonic bacteria in patients with SBS as well as an increase in the concentration or activity of various enzymes, such as β-galactosidase, over time during the adaptation period.⁵⁸ Because SCFAs stimulate sodium and water absorption,⁴² patients might be expected to experience decreased fecal fluid and sodium loss, but this has not been observed clinically.⁵⁷

Vitamins 

Micronutrients often require supplementation (Table 2).

Table 2. Vitamin and Mineral Supplements for Patients With Short Bowel Syndrome

NOTE. The table lists rough guidelines only. Vitamin and mineral supplementation must be monitored routinely and tailored to the individual patient, because relative absorption and requirements may vary.

Because water-soluble vitamins are absorbed in the proximal jejunum, it is unusual for deficiencies to develop in short bowel patients (except in those who have high jejunostomies or duodenostomies), although these patients generally require TPN. Thiamine deficiency has been reported and became an important issue during a recent parenteral vitamin shortage.⁵⁹ Patients have presented with Wernicke's encephalopathy, beriberi, and severe metabolic alkalosis.⁶⁰ If thiamine deficiency is suspected, whole blood thiamine concentration is not helpful; this reflects recent nutritional intake. Erythrocyte transketolase activity should be determined and empiric therapy begun with 100 mg of parenteral thiamine daily. Biotin deficiency has rarely been reported in patients with SBS.⁶¹ It is manifested in a scaly dermatitis, alopecia, lethargy, hypotonia, and lactic acidosis. Therapy consists of parenteral biotin supplementation of 0.3-1 mg daily, although this is not currently commercially available. Vitamin B₁₂ supplementation is required (300 μg/month SQ) in patients who have had a significant portion of their terminal ileum resected (>60 cm).⁶² Folic acid is provided as a constituent of parenteral multivitamins. However, in patients with proximal jejunal resections, folate deficiency may develop.⁶³ Such patients should receive 1 mg/day supplement.

Fat-soluble vitamin deficiency (A, D, and E) is more common because of the steatorrhea that occurs in SBS and the subsequent decrease in micellar formation and fat digestion.⁶⁴ The use of cholestyramine may also result in fat-soluble vitamin deficiency.⁶⁵ Night blindness and xerophthalmia has been described in SBS.⁶⁶ As vitamin A deficiency progresses, corneal ulceration and permanent visual loss may ensue, and short bowel patients who do not receive parenteral multivitamins should have their serum vitamin A concentration monitored. If a low-serum vitamin A concentration is detected, therapy is 10,000-50,000 units daily, and may be administered either orally or parenterally.

Vitamin D deficiency manifests in osteomalacia. Usually dietary intake is a relatively unimportant source of vitamin D because the majority is endogenously synthesized from 7-dehydrocholesterol via ultraviolet light.⁶⁷, ⁶⁸ However, because enterohepatic circulation is disrupted in patients who have undergone significant ileal resections, deficiency may result.⁶⁹

Vitamin E deficiency in patients with SBS may manifest in hemolysis⁷⁰ and various neurological deficits.⁷¹ Because serum vitamin E concentration reflects serum total lipid concentration, which may be low in short bowel patients, a low serum vitamin E concentration alone may not be indicative of a deficient state; the ratio of serum vitamin E to total lipid should be calculated.⁷², ⁷³

Vitamin K is synthesized by colonic bacteria (60%),⁷⁴ although dietary intake accounts for about 40% of requirements; deficiency is therefore uncommon in patients with intact colon. However, vitamin K deficiency is frequent in patients who have no residual colon or have been given recent broad-spectrum antibiotics. Requirement is ≅1 mg daily.⁷⁴ Vitamin K only recently has been a constituent in adult multivitamins for TPN, although pediatric multivitamin formulations all contain vitamin K.

Trace metals 

Patients with SBS lose a significant amount of zinc and selenium in their feces. A significant amount of zinc is lost in small bowel effluent (12 mg/L small intestinal fluid and 16 mg/L stool).⁷⁵ Zinc deficiency has been associated with growth abnormalities,⁷⁶ delayed wound healing,⁷⁷ and cellular immunity dysfunction.⁷⁸ Patients in whom zinc deficiency is suspected should be treated empirically with oral zinc sulfate (220-440 mg daily) or parenteral zinc if the patient requires TPN. Serum and leukocyte measurements of zinc concentration, although helpful, may be unreliable.⁷⁹ Selenium deficiency has been associated with cardiomyopathy,⁸⁰ peripheral neuropathy, proximal muscle weakness and pain,⁸¹ whitening of the hair, and macrocytosis.⁸² Serum selenium is a reliable indicator of selenium status, and if low, oral or parenteral supplementation should be provided. Although there are 3 reported possible cases of chromium deficiency in patients requiring long-term TPN,⁸³ deficiency has not been reported in short bowel patients who do not require TPN; therefore, routine supplementation is not recommended. Chromium is a necessary cofactor for insulin's effects in peripheral tissue.⁸⁴ Even as TPN is a concern, available evidence suggests there is sufficient chromium present in the TPN solutions as a contaminant, and supplemental chromium may invite the possibility of nephrotoxicity.⁸⁵ Copper deficiency is very rare in the patient with SBS. Deficiency may result in microcytic anemia, neuropathy, and decreased fertility.⁸⁶

Medication absorption 

The provision of medications to the patient with SBS can represent a challenge to the practicing clinician. Just as fluid and nutrient absorption is impaired, medication absorption is often impaired as well. As with nutrient absorption, significant interpatient variability may be observed. Given that the risk for catheter sepsis is greater the more times the line is manipulated, it is important to use the oral or enteral route for medication delivery whenever possible. The degree to which a medication is malabsorbed is dependent upon several variables. These include the surface area and health of the residual intestinal surface area, morphologic and physiologic factors, including the presence or absence of the terminal ileum (B₁₂ and bile salt absorption—necessary for cyclosporin absorption), or the presence of an acidic or alkaline environment (related to the use of H₂ blockers in TPN or use of proton pump inhibitors). Many, but not all, medications are absorbed in the jejunum; so, for many medications, absorption will be minimally impacted in the absence of decreased intestinal transit time, which will decrease mucosal contact time. Most of the available data on oral medication absorption in patients with SBS is in the form of isolated case reports.⁸⁷

Fluid and electrolyte management 

Massive enterectomy is associated with transient gastric hypersecretion. Basal acid secretion is significantly increased up to the first few months following resection.⁸⁸, ⁸⁹ Massive small bowel resection is associated with hypergastrinemia during the initial first 6 months after surgery.⁹⁰ The H₂ antagonists and proton pump inhibitors are useful in reducing gastric fluid secretion, and therefore will also reduce fluid losses during this period.¹⁷, ⁹¹, ⁹², ⁹³, ⁹⁴ However, absorption of orally dosed medications may be impaired, and either large doses, oral medication, or intravenous delivery may be required. Although fluid losses are decreased, macronutrient and electrolyte absorption are not affected by H₂ antagonists and proton pump inhibitors.

Fluid losses usually require chronic control with anti-motility agents, such as loperamide hydrochloride or diphenoxylate. Typical doses are 4-16 mg/day. If these are ineffective, especially in patients with no colon in continuity or those who are left with a minimum of residual jejunum or duodenum, codeine sulfate or tincture of opium may be necessary. The usual dose for codeine sulfate is 15-60 mg two to three times a day. Rarely, patients will require treatment with octreotide. The mechanism of action is unclear, but octreotide may be useful to slow intestinal transit time and increase water and sodium absorption.⁹⁵, ⁹⁶ In one open-labeled study of 9 patients with end-jejunostomies, daily jejunostomy volume was reduced from 8.1 ± 1.8 to 4.8 ± 0.7 L/day using a dose of 100 μg SQ, three times daily 30 minutes before meals.⁹⁷ Because use of octreotide does not lead to the discontinuation of TPN, its use should be reserved for patients with high output jejunostomies in whom fluid and electrolyte management is problematic. Octreotide reduces splanchnic protein synthesis, thereby reducing mucosal protein incorporation and villus growth rate, and may impair postresectional intestinal adaptation.⁹⁸ There is also an increased risk for cholelithiasis⁹⁸, ⁹⁹ in a patient group already predisposed to this problem.¹⁰⁰

Glucose-polymer-based ORS should be instituted to decrease dehydration and to decrease TPN fluid requirements in patients with residual jejunum ending in a jejunostomy. Patients with <100 cm of residual jejunum are at significant risk for dehydration because they secrete more Na and fluid than consumed orally.⁹¹ Because the jejunum is permeable to Na and chloride (Cl), passively absorbed solutions with high NaCl concentration are readily absorbed. Glucose promotes salt and water absorption by solvent drag.¹⁰¹ However, Na and water are not absorbed from hypotonic or isotonic solutions in the jejunum. Several commercially available ORS formulas are available, although probably the best, and certainly the least expensive, is the one recommended by the World Health Organization (WHO).¹⁰² This can be formulated by dissolving the following in 1 L tap water: NaCl (2.5 g), KCl (1.5 g), Na₂CO₂ (2.5 g), and glucose (table sugar, 20 g). Only the KCl requires a physician prescription. Most, if not all, of the commercially available ORS have substantially less Na (range, 45-50 mmol/L). NaCl may be added; the optimal Na concentration should be at least 90 mmol/L, which is the usual concentration of small bowel effluent.¹⁹ Solutions with lower Na concentrations lead to increased Na losses. Therefore, patients with SBS should be cautioned against consumption of plain water and should be encouraged to drink ORS whenever they are thirsty. More recent evidence has shown that hypotonic (160 mOsmol/kg) ORS leads to decreased intraluminal duodenojejunal fluid flow rate in normal volunteers, although the effect on gastrointestinal fluid losses or patient hydration status in short bowel patients has not been evaluated.¹⁰³

For patients with residual colon in continuity, ORS may still be of value, but, provided sufficient Na is present in the diet, the amount of Na in the ORS may not be as critical since the colon readily absorbs Na and water against a steep electrochemical gradient.¹⁰⁴ For patients with no remaining jejunum, but who have residual ileum, the presence of glucose in the ORS is not critical because ileal water absorption is not affected by the presence of glucose.¹⁰⁵

In addition to Na losses, significant quantities of Mg are lost in jejunal or ileal effluent as well.¹⁰⁶ Patients may develop Mg deficiency despite a normal serum concentration; therefore, it is prudent to measure 24-hour urine Mg loss.¹⁰⁷ The median 24-hour urine Mg in normal volunteers in the study was 127 mg (vs. 19 mg for Mg deficient short bowel patients).

Mg deficiency may precipitate Ca deficiency because hypomagnesemia impairs the release of parathyroid hormone.¹⁰⁸ In addition, the majority of patients with SBS who do not require TPN are in negative Ca balance.¹⁰⁹ Therefore, in the absence of TPN, oral Ca supplementation is routinely recommended (800-1200 mg per day). Mg replacement is problematic. Attempts with oral MgO or oral consumption of injectable Mg have generally not been successful and have been associated with increased fecal loss because of their cathartic effect.¹¹⁰ Although Mg gluconate is water soluble, Mg has generally not been a constituent of ORS. Therefore, some patients may require periodic parenteral Mg despite the absence of a TPN or intravenous fluid requirement. Iron is absorbed in the duodenum; therefore, in the absence of hemorrhage it is not routinely required as a supplement. Phosphorous deficiency is not well described in SBS, and therefore supplementation is rarely, if ever, required.

Pharmacologic enhancement of intestinal adaptation 

The GLP-II is another hormone secreted from L cells (as well as from pancreatic A cells). Postprandial serum GLP-II concentration is not unexpectedly depressed in patients who have had extensive small bowel resection, especially including ileum.¹¹¹ It has been postulated that the relative lack of jejunal hypertrophy following ileal resection¹¹², ¹¹³ may be at least partly related to the resection of GLP-II-producing L cells, although these investigations were undertaken in patients over 2 years following their resection without a baseline comparison. GLP-II (400 μg SQ, twice a day for 35 days) was administered in a small, pilot, open-labeled trial to 4 patients with SBS without residual colon who required TPN and in 4 patients with sufficient residual jejunum where TPN was not required.¹¹⁴ Jejunal villus height and crypt depth tended to increase (although not significantly), energy absorption tended to increase (nonsignificantly), and fecal wet weight decreased, indicating increased fluid absorption. Although GLP-II is not commercially available, investigational studies of a longer-acting, genetically engineered analogue of GLP-II are underway. Growth hormone administration (0.5 IU/kg per day or 0.024 mg/kg per day) alone for 8 weeks had no affect on absorptive capacity of energy, protein, or fluid in 10 patients (4 with colon in continuity).¹¹⁵

Dietary restriction 

Normally, oxalate in the diet binds to dietary calcium and is excreted in the stool. However, in the presence of significant fat malabsorption, dietary calcium preferentially binds to free fatty acids, rendering the oxalate free to pass into the colon. Dietary oxalate is absorbed to a minimal extent in the small intestine, but can be absorbed more readily in the colon. Absorption may also be enhanced because colonic permeability increases secondary to injury from malabsorbed bile salts also passing into the colon.¹¹⁶ Once absorbed into the colon, oxalate is renally filtered, where it binds to calcium, resulting in hyperoxaluria and calcium oxalate nephrocalcinosis and nephrolithiasis.⁸ Therefore, in patients with SBS who have colon in continuity, oxalate should be restricted in the diet. Table 3 lists the relative oxalate content of many foods.

Table 3. Oxalate Content of Foods

Data from Ney DM, Hofmann AF, Fischer C, Stubblefield N. The Low Oxylate Diet Book. University of California, San Diego, California, 1981.

Massey LK, Roman-Smith H, Sutton RA. Effect of dietary oxalate and calcium on urinary oxalate and risk of formation of calcium oxalate kidney stones. J Am Diet Assoc 1993;93:901-906.

Holmes RP, Kennedy M. Estimation of the oxalate content of foods and daily oxalate intake. Kidney Int 2000;57:1662-1667.

Zarembski PM, Hodgkinson A. The oxalic acid content of English diets. Br J Nutr 1962;16:627-634.

Kasidas GP, Rose GA. Oxalate contents of some common foods; determination of by an enzymatic method. J Hum Nutr 1980;34:255-266.

Oral Ca supplements may also be of value for the prevention of Ca-oxalate nephrolithiasis.¹¹⁷ Hyperoxaluria may also develop in patients without colon who are TPN-dependent.¹¹⁸ This is most likely related to metabolism of vitamin C in the TPN solution, in the presence of light, to oxalate.¹¹⁹ Therefore, it may be beneficial to shield TPN to which vitamin C has been added either as a multivitamin solution or individually, but it remains unclear if dietary oxalate should be restricted in all patients with an end jejunostomy who require TPN.

Providing parenteral nutrition 

Macronutrients 

Most patients will require TPN, at least initially. For the normally nourished patient, TPN should be supplied at 25-30 kcal/kg per day based on ideal body weight for adults, with greater levels of support for infants and children depending upon age. Dextrose is a monohydrate, providing 3.4 kcal/ml. The maximum dextrose infusion rate should be 5-7 mg/min.¹²⁰ Blood glucose should be monitored at least daily, and optimally 4 times a day, and should be <180-200 mg/dL; the addition of regular insulin to the TPN solution may be required. If insulin is required, it should be added to the TPN bag at an initial dose of 0.1 U/g of dextrose, with subsequent adjustments made as necessary. Intravenous lipids are generally used to provide 20%-30% of infused calories, although a greater percentage of lipid may be used in the patient with significant glucose intolerance or fluid management issues; 20% lipid emulsion is more calorically dense than dextrose. Generally, the percentage of lipid calories should be increased and the percentage of dextrose calories decreased if the amount of supplemental insulin required exceeds 0.2 U/g of dextrose, although the serum triglyceride concentration should be kept under 700-800 mg/dL, and optimally, <400 mg/dL. Protein is supplied in the form of amino acids, and should be supplied at 1.0-1.5 g · kg⁻¹ · day⁻¹, based on ideal body weight for adults, with greater levels of support for infants and children depending upon age.

Getting the patient ready for home TPN 

Initially, TPN is infused continuously while postoperative complications are addressed and metabolic issues stabilized. Attempts should be made, when appropriate, to wean patients who have sufficient absorptive capacity (as discussed above), being mindful that maximal adaptation may take as long as 1-2 years (as alluded to above). For patients who will require TPN at home, the TPN infusion should be compressed to nighttime infusion. Typically, this would be over a 10-hour period with an additional 30-60-minute taper period; some patients with fluid management issues from renal failure or congestive heart failure will be unable to tolerate this infusion rate. Because pancreatic insulin secretion requires some period to adapt to the significant dextrose infusion, cycling should be a gradual process. Once the goal infusion volume has been determined (e.g., 1.5, 2.0, 2.5, or 3.0 liters for adults; with less volume for infants and children), the total volume should be infused over gradually decreasing time periods (e.g., compress by increments of 2-4 hours daily). TPN should be infused ideally via a single lumen catheter with its tip positioned in either the superior vena cava (SVC) or inferior vena cava (IVC) to decrease the risk of infection and thrombosis.¹²¹, ¹²² Tunneled catheters, including Hickman, Broviac, or Groshong catheters, implantable ports, or percutaneously inserted central catheters should be used at home, although the experience with percutaneously inserted central catheters for >1 year at home is minimal. To qualify for Medicare reimbursement, home TPN must be required for at least 3 months, fat malabsorption must be documented, and enteral feeding must have failed.

The patient's home environment should be evaluated. A room, preferably the bedroom—definitely not a “dirty” room, such as the kitchen or bathroom—should be identified for TPN to be set up prior to use. The patient should be instructed to purchase a small refrigerator, which will be used solely for the storage of TPN solutions. A local support group under the umbrella of the Oley Foundation (1-800-776-OLEY or oley.org) should be contacted. The Oley Foundation is an independent, nonprofit organization of patients and professionals that provides information, outreach services, emotional support, and conference activities to patients who require home TPN as well as their families and health care professionals involved in their care. The transition from hospital to home may be smoother if the patient has another patient contact who has previously undergone the same process. It is generally advised that the patient should undergo some education about TPN prior to hospital discharge. This should include the indications for TPN, basic instruction on getting their solutions ready for use (they will need to add their vitamins, insulin, H₂ blockers if prescribed, and flush catheter), catheter care, dressing changes, and information on their intravenous pump. It is often useful for the patient to meet their home care nurse (who will continue the education process at home until the patient or caregiver is self-sufficient), prior to discharge. The treating physician should have some familiarity with appropriate catheter care and the identification of complications associated with long-term TPN, including catheter-related infections, occlusions, and metabolic complications. These are beyond the scope of this review, but have recently been reviewed elsewhere.¹²³, ¹²⁴ (Catheter-related infections and thrombosis are discussed in greater detail under complications of parenteral nutrition that may make intestinal transplantation necessary.) Algorithms 1 and 2 describe the evaluation and treatment of fever in the home TPN patient and algorithm 3 describes the evaluation and treatment of catheter occlusion in the home TPN patient, which may be either thrombotic or non-thrombotic in origin.

• 
  • View Large Image
  • Download to PowerPoint

• Algorithm 1. Diagnosis and treatment of catheter occlusion.

• 
  • View Large Image
  • Download to PowerPoint

• Algorithm 2. Catheter-related infection algorithm for diagnosis and treatment.

• 
  • View Large Image
  • Download to PowerPoint

• Algorithm 3. Management of short bowel syndrome.

Patients should not be discharged home until their fluid and electrolyte requirements have stabilized. Once home, office visits and laboratory monitoring will initially be more frequent, although the stable patient who has minimal difficulty generally can visit the office and have routine laboratory testing done as infrequently as 3 times a year. The goal is to return patients to society. Home TPN should not prevent a patient from working or traveling.

Patients in whom TPN is being weaned, and who acquire <75% of the nutritional needs parenterally, should have vitamin (usually the fat-soluble vitamins) and trace metal (Zn, Cu, Se) analyses performed 2 or 3 times yearly, and whenever possible deficiencies have been clinically recognized. Vitamin K is not a constituent of all parenteral multivitamin solutions, although vitamin K is present in the intravenous lipid emulsion. Therefore, the prothrombin time should be regularly monitored, especially in those patients who lack residual colon. During the clinic visit, the catheter exit site or skin overlying an implanted infusion port should be examined for warmth, erythema, and tenderness, and the catheter dressing should be examined for purulent exudate, which may signal infection. A properly maintained catheter may remain in place indefinitely.¹²⁵

Quality of life and survival of short bowel patients 

No quality of life data exists for patients with SBS who do not require TPN. In addition, Oley Foundation surveys and similar surveys from home TPN programs in Europe include all home TPN patients. Patients with SBS were not analyzed separately in these surveys. In a study of 124 consecutive adult short bowel patients with nonmalignant diseases at 2 centers in France, survival was 86% at 2 years and 75% at 5 years.⁷ TPN-dependence was 49% at 2 years and 45% at 5 years. Those patients with end-enterostomy or <50 cm had significantly lower survival rates. TPN dependence was related to remaining bowel length and/or absence of ileocolic anastomosis. A review of the 225 patients treated in the Mayo Clinic home TPN program showed similar survival.¹²⁶

Complications of long-term TPN 

Hepatic complications 

Liver abnormalities are a recognized complication in long-term TPN patients and can present as a broad spectrum of pathologic entities, including steatosis, cholestasis, steatohepatitis, fibrosis, and cirrhosis.¹²⁷, ¹²⁸, ¹²⁹, ¹³⁰, ¹³¹, ¹³² A recent report from the USA suggested that 15% of patients receiving TPN for >1 year will develop end-stage liver disease (ESLD), which is associated with 100% mortality within 2 years of onset.¹³³ Another recent report from France¹³¹ suggested that >50% of adult patients on TPN for >5 years will develop complicated liver disease (e.g., severe fibrosis [grade 2], cirrhosis, or one of the following: bilirubin >3.5 mg/dL for >1 month, ascites, portal hypertension, hepatic encephalopathy, portal hypertension, or liver failure with Factor V <50%), although this study also included patients with chronic hepatitis B and C. In France, all home TPN patients are managed and monitored by government authorized regional home TPN centers. Therefore, these results may be more representative of what occurs in an entire population of home TPN patients than other center specific studies.

Liver complications appear to be especially prevalent in pediatric patients on long-term TPN.¹³² Those patients with the shortest residual intestine are at greatest risk for development of eventual ESLD.¹²⁷, ¹²⁸ Recent investigations have suggested the liver disease associated with long-term TPN is most likely caused by malabsorption or insufficient production of the nutrient required for normal hepatic function, rather than a toxic effect of TPN.¹³⁴, ¹³⁵, ¹³⁶

Investigational studies using oral lecithin, ursodeoxycholic acid or intravenous choline to treat or prevent the development of TPN-associated liver disease should be considered.¹³⁴, ¹³⁵, ¹³⁶, ¹³⁷, ¹³⁸ Otherwise, no specific therapy is available. Care should be taken to avoid dextrose overfeeding¹³⁹ fatty acid deficiency from insufficient intravenous lipid emulsion (minimum of 2%-4% or 4%-8% of non-protein calories as linoleic acid or lipid emulsion, respectively),¹⁴⁰ and to limit intravenous lipid intake to <2.5 g/kg per day, possibly even to <1 g/kg per day.¹³¹ Neither carnitine deficiency nor carnitine supplementation appear to have any role.¹⁴¹

Biliary complications 

Given the development of macronutrient malabsorption in patients with SBS, such patients should be encouraged to increase their overall food intake. Oral intake of food is also important to prevent development of biliary sludge, which is a precursor for cholelithiasis in patients with SBS.¹⁴², ¹⁴³ Gallstones which form in patients with significant ileal resections and SBS are usually calcium bilirubinate, and form at a rate 3 times greater than in patients without previous resection.¹⁴⁴, ¹⁴⁵ The pathogenesis of calcium-bilirubinate gallstones in patients with SBS is unclear. Postmeal stimulated serum cholecystokinin (CCK) concentration is depressed in some patients with SBS,¹⁴⁶ although this has not been shown in all studies.³⁰ CCK injections have been used experimentally in an attempt to induce gallbladder contraction and thereby prevent gallstone formation,¹⁴⁷ but this has not been universally successful.¹⁴⁸ In addition, CCK injections have been commonly associated with nausea, vomiting, and abdominal pain.¹⁴⁷, ¹⁴⁸

Catheter-related infections 

The Oley Foundation registry data indicates that on average, TPN patients were hospitalized for infectious complications approximately once per year.¹⁵ Unfortunately the registry did not identify what percentage of these admissions were for catheter-related infections, nor did they indicate how many catheter-related infections were managed without hospital admission. Messing et al. found intestinal failure patients on permanent TPN to have a high mortality rate (>50% with median follow-up of 64 months), with 31% of deaths attributable to sepsis.⁶ In this series, the central venous catheter (CVC) was clearly identified as the source of sepsis in 50% of septic deaths. Other centers have reported that with experience and proper line care technique, the rate of catheter-related infections in patients receiving HPN for gastrointestinal disorders can be as low as 0.8 infections per 1000 catheter days (including catheter sepsis, exit site, and tunnel infections) during 1154 patient years of follow-up and 1.4 infections per 1000 catheter days for children in 241 years of patient follow-up.¹²¹ (Refer to algorithm 2 for management of catheter-related infections.)

D-lactic acidosis 

Lactobacilli and other bacteria, including Clostridium perfringens and Streptococcus bovis, when present, ferment non-absorbed carbohydrate to D-lactic acid, which cannot be metabolized by D-lactate dehydrogenase. These organisms may proliferate in an acidic environment that may be promoted by the metabolism of unabsorbed carbohydrate to SCFAs. A severe metabolic acidosis, encephalopathy, headache, ataxia, and dysarthria may develop in the absence of hepatic dysfunction if significant absorption of D-lactic acid occurs.²⁹ Thiamine deficiency should be excluded.¹⁴⁹, ¹⁵⁰ D-lactate concentrations will be increased in blood and urine (L-lactate concentration, which is usually measured when serum lactate concentration is ordered, is normal). The mechanism for the neurological symptoms is unknown. Fortunately, this complication is very rare. Treatments described in case reports have included nothing (with spontaneous resolution), oral metronidazole, neomycin, vancomycin, (for 10-14 days), and avoidance of “refined” carbohydrates.¹⁵¹, ¹⁵²

Catheter occlusion 

The long-standing requirement for a CVC in intestinal failure patients predisposes to thrombus and/or fibrin formation and ultimately occlusion of central veins. Catheter occlusion may also result from TPN solution incompatibilities. Refer to algorithm 2 for evaluation and treatment of patients with CVC occlusions. The Oley Foundation registry did not provide data for all central vein occlusions, but did indicate that the SVC thrombosis resulted in <0.3 hospital admissions per patient year. Moukarzel et al. found that in long-term pediatric TPN patients, the mean life span of a CVC was 22.4 ± 14.7 months (range, 1.5-178 months) and 25% of catheter removals were for thrombotic complications.¹⁵³ In many long-term TPN patients, the central veins being utilized will eventually occlude and as new veins are used, multiple central venous occlusions can occur. The incidence of catheter thrombosis is ≅0.2 episodes per 1000 catheter days in 1154 years of patient follow-up.¹⁵⁴ Prior catheter thrombosis is a risk factor for development of SVC/IVC syndrome in the future; therefore, warfarin anticoagulation should be undertaken in patients with prior catheter thrombosis in the absence of catheter malposition as the cause.¹⁵⁴ Typically, TPN catheters are first placed in the SVC by accessing either the internal jugular, brachial, or subclavian veins. If these veins are no longer accessible, the catheters are usually placed in the IVC via the femoral or saphenous veins. Other life-threatening complications can be associated with the progressive loss of venous access, including SVC syndrome, pulmonary embolus, and septic thrombi.¹²², ¹⁵⁴, ¹⁵⁵, ¹⁵⁶, ¹⁵⁷ True loss of catheter insertion sites is extremely rare; clinicians often prematurely determine that a patient has no suitable venous access. When all the usual central veins have been exhausted, alternatives include translumbar or transhepatic access to the IVC, and thoracotomy with direct placement of an intra-atrial catheter among others.¹⁵⁸, ¹⁵⁹, ¹⁶⁰ In the 1154 patient years experience previously described at a single institution, no patient ever lost CVC access and only 2 required right atrial catheter placement during that time period.¹⁵⁴

Other complications 

Renal dysfunction,¹⁶¹ metabolic bone disease,¹⁶² memory deficits,¹⁶³ and neurological problems have also been described in patients who require long-term TPN.¹⁶⁴

Back to Article Outline

Role of surgery 

Nontransplant surgery 

The primary emphasis of nontransplant surgery in SBS is to increase nutrient and fluid absorption by either slowing intestinal transit or increasing intestinal surface area. The goal is similar to that of medical therapy, which is to reduce the requirement for TPN. Medical and surgical therapy often exhibit a symbiotic relationship. Various surgical procedures have been described in case reports and series only (Table 4). There are no studies comparing surgical and medical approaches.

Table 4. Intestinal Lengthening Surgery

CInt, colonic interposition; I-Values, intestinal valve; LILT, longitudinal intestinal lengthening and tailoring; NR, not reported; SRSB, segmental reversal small bowel.

Restoration of intestinal continuity, such as re-anastomosis of small intestine with colon, should be done whenever possible, since it can be performed with relatively low morbidity and mortality (often with good success of discontinuation of parenteral nutrition). This allows for colonic fermentation of unabsorbed carbohydrate from the small intestine and an important source of energy assimilation (see role of soluble fiber). The other forms of surgery for SBS are more technically challenging and should only be considered in select patients. In general, the results are not particularly encouraging, although individual patients with specific criteria (as described below) may benefit.

Operations to slow transit include segmental reversal of the small bowel, colonic interposition, construction of valves, and electrical pacing of the small intestine. Approximately 40 cases of segmental reversed small bowel (SRSB) have been reported.¹⁶⁰, ¹⁶¹, ¹⁶², ¹⁶³, ¹⁶⁴, ¹⁶⁵, ¹⁶⁶, ¹⁶⁷, ¹⁶⁸, ¹⁶⁹, ¹⁷⁰, ¹⁷¹, ¹⁷², ¹⁷³, ¹⁷⁴, ¹⁷⁵ Unfortunately, most cases are antidotal, without long-term patient follow-up. The surgical technique works on the premise of decreasing intestinal transit by creating a short antiperistaltic segment of small intestine. There is general agreement by most authors that SRSB should not be performed at the time of the initial resection, but at a later time (e.g., during surgery for restoring intestinal continuity). This allows time for intestinal adaptation to occur, which may eliminate the need for surgery. The length of intestine reversed should be ≅10 cm. Shorter segments may be insufficient in slowing transit and longer segments may result in intestinal obstruction. In addition, the reversed segment should be located in the most distal part of the small intestine to eliminate the possibility of obstructive symptoms. A limitation of SRSB is that patients may have only a very short segment of residual small bowel, which may not allow resection of a 10-cm segment for reversal. In a report of 8 short bowel patients (mean age, 58 years) treated with SRSB, 4 of 8 patients were able to discontinue parenteral nutrition.¹⁷⁵ Discontinuation of parenteral nutrition was not immediate, with a median of 8 months after surgery. There were no postoperative deaths directly related to the surgery. Three of the patients experienced transient intestinal obstruction.

A colonic segment can be interposed between small intestine in either an isoperistaltic or antiperistaltic direction. Both methods have been reported to slow intestinal transit and increase absorption in animal models. The use of colon interposition has been reported in 12 patients (11 isoperistaltic segments); all but 1 were infants <1 year of age.¹⁷⁶, ¹⁷⁷, ¹⁷⁸, ¹⁷⁹, ¹⁸⁰ Lengths of colon have ranged between 8 and 24 cm. Four of the infants and 1 adult were reported to have good outcomes in terms of discontinuing parenteral nutrition 4 months after surgery.¹⁷⁷, ¹⁷⁸, ¹⁷⁹ Colon interposition was not associated with any perioperative mortality or morbidity.¹⁷⁸ The antiperistaltic placed colon does not appear as successful as an isoperistaltic segment.¹⁷⁶ Clinical and experimental experience with colonic interposition remains limited.

Construction of intestinal valves is another surgical method to slow intestinal transit in SBS. Clinical experience with intestinal valves is much less than for reversed small intestine segments.¹⁸¹, ¹⁸², ¹⁸³ The valves create a partial mechanical obstruction and disrupt the normal motility of the small intestine, and prevent retrograde reflux of intestinal contents. Experimental studies have reported delayed transit, dilation of proximal intestine, and increased absorption. Nipple valves have been placed in 6 infants to increase intestinal lengthening.¹⁸¹ Intussuscepted valves have been reported in 5 adults and 1 infant with short bowel.¹⁸¹, ¹⁸², ¹⁸⁴ Four of the patients had significant improvement and the others required removal of the valve because of mechanical obstruction. Durability of valves to serve as sphincters has been questioned.

Recirculating loops and retrograde intestinal pacing have been met with limited success.¹⁷¹, ¹⁸⁵, ¹⁸⁶, ¹⁸⁷ Objective evidence of increased absorption with both has not been confirmed. Obstruction and stasis contribute to the failure of recirculating intestinal loops.

Intestinal surface area may be increased by the longitudinal intestinal lengthening and tailoring (LILT) procedure. Bianchi first described the technique of LILT in 1980.¹⁸⁸ Since then, ≅100 such surgeries have been reported in the literature, predominately in children with short bowel.¹⁸⁹, ¹⁹⁰, ¹⁹¹, ¹⁹², ¹⁹³ It is most useful in children with significantly dilated residual intestine in whom dysmotility is present, often with secondary bacterial overgrowth. This surgery includes isolation of the dual blood supply to the small intestine by separation of the mesenteric borders, followed by longitudinal division of the bowel with isoperistaltic end-to-end anastomosis, thereby effectively doubling the length of bowel. The indication for performing LILT is to prevent the need for long-term TPN and its associated complications, including ESLD. Patient selection for LILT surgery include: (1) intestinal diameter >3 cm; (2) length of residual small bowel >40 cm; (3) length of dilated bowel >20 cm; (4) parenteral nutrition dependent; and (5) absence of liver failure.¹⁸⁹ A recent study of 16 infants and children reported significant improvement in stool volume, intestinal transit time, and D-xylose and fat absorption after lengthening the small intestine by ≅42%.¹⁸⁷ Of these 16 patients, 14 could be weaned off parenteral nutrition. Bianchi reported similar results.¹⁸⁹ Some patients have remained off parenteral nutrition as long as 10 years following LILT. Anastomotic stenosis is the most common complication reported with this operation, reported in ≅10% of patients.¹⁸⁹ There is very limited experience with this procedure in adults.

Intestinal transplantation 

Intestinal transplantation is a therapeutic option for patients with intestinal failure. While clinical experience was limited to few case reports prior to the 1990s, the world experience now includes ≅500 intestinal transplants (2/3 in pediatric patients), with the number performed per year increasing every year since 1994. So far, intestinal transplants have been performed only in situations where no other therapeutic alternatives were thought to be available. Therefore, there are no randomized controlled studies (Type I data) comparing intestinal transplantation to other therapies, and very few retrospective case-control studies that would qualify as type II data. Most available data is based on retrospective analyses of national and international registries, individual center experiences, and individual case reports.

Indications for transplantation 

Thus far, intestinal transplants have only been performed in patients who have developed life-threatening complications attributable to their intestinal failure and/or long-term TPN therapy.¹⁹⁴ Until recently, there had been no official policy by a third-party payer regarding intestinal transplantation; Medicare has now approved payment for intestinal transplants in patients who fail TPN therapy (Medicare Coverage Policy Decisions—Intestinal and Multivisceral Transplantation [CAG-00036], Oct. 4, 2000). The Health Care Finance Administration (HCFA) based their decision on a review of 3 independent evaluations of the medical literature: (a) data submitted by the unnamed requestor, (b) a 1999 technology assessment performed by the Blue Cross Blue Shield Association's Technology Evaluation Center, and (c) a separate technology assessment performed by the Center for Practice and Technology Assessment at the Agency for Health Care Research and Quality (AHRQ). Medicare has defined “Failure of TPN therapy” by the development of 1 or more of the following complications:

Outcomes of patients waiting for intestine transplants 

Intestinal transplant candidates in need of a cadaver donor are placed on the United Network of Organ Sharing (UNOS) waiting list. The UNOS database maintains waiting list data for all solid organs.¹⁹⁶ UNOS data reveals that although the waiting list for intestinal transplants is still fairly small (151 patients on the last day of 2000), it has continued to grow every year since 1993. Average patient waiting times for intestine transplants range from 201 to 343 days depending on their ABO blood group. For patients on the intestinal transplant waiting list, 77% must wait longer than 3 months and 44% longer than 1 year to receive a transplant. While these waiting times compare favorably to those for most other organs,¹⁹⁷ the death rate on the waiting list for intestinal transplants is significantly higher than that seen on any other solid organ transplant waiting list (Table 5).¹⁹⁶, ¹⁹⁷ Of the 192 deaths that have occurred since 1993 in patients waiting for intestinal transplants, all but 12 have been in patients who also needed livers (Table 6).

Table 6. Deaths of Patients on Liver Transplant Waiting List in Candidates Requiring Combined Intestine/Liver Transplants, Based on UNOS Medical Urgency Status at Time of Death

Therefore, while patients waiting for an isolated intestine do well on the waiting list, those who also need a liver often do poorly.

Table 5. Comparison of Liver Transplant Waiting List Death Rates Between Liver Only Candidates and Intestine/Liver Candidates

A brief explanation of the factors that influence the intestine/liver transplant waiting list logistics is essential to further analyze this high waiting list mortality. Patients who require an isolated intestine transplant are placed on the intestine waiting list. If they require both a liver and an intestine transplant, they are also placed on the liver waiting list, and the intestine will be automatically included when they are allocated the liver (based on their status on the liver waiting list). However, if they are offered an intestine based on their status on the intestine waiting list, they will not be automatically assigned a liver. Therefore, in patients who need both organs, it is their status on the liver waiting list, rather than their status on the intestine waiting list, that determines organ availability. Similarly, when multiple organs, including the liver and the intestine, are required, allocation of the additional organs is driven by the liver allocation process.

Priority on the liver waiting list is primarily determined by the UNOS status. A patient's UNOS status is determined by the perceived medical urgency and is based on their risk of dying on the wait list. Until recently, this was based on their Child-Turcotte-Pugh (CTP) score and specific coexistent complications of ESLD (uncontrolled variceal bleeding, hepatorenal syndrome, intractable ascites or hydrothorax, intractable hepatic encephalopathy, spontaneous bacterial peritonitis). This scoring system has been replaced by the Model for End-stage Liver Disease (MELD) system.¹⁹⁸ Retrospective analysis of UNOS liver waiting list mortality data indicates that the prior CTP score-based UNOS status system did not effectively prioritize intestine/liver candidates (see below). Sufficient data is not yet available to demonstrate if the MELD system is superior as a mortality predictor for wait-listed intestine/liver candidates.

The waiting time for liver transplant candidates varies significantly, but has a direct correlation to their UNOS status. In 2000, the median waiting time for liver transplantations was 7 days for Status 1 (the sickest, highest priority patients) and 36 days for Status 2A (second highest priority). Patients in all UNOS statuses except Status 1, who needed both an intestine and a liver, have had a higher waiting list mortality than patients listed for a liver only. The higher waiting list mortality applied to all age groups (Table 5). Despite their higher mortality, liver transplant candidates with coexistent SBS and/or TPN failure who also need intestine transplants do not currently receive special priority on the liver waiting list. In 1998 and 1999, the vast majority (85%) of waiting list deaths in candidates needing both intestines and livers occurred in patients who were prioritized as Status 2B or less on the liver waiting list (Table 5). More recent UNOS data specifically pertaining to liver/intestine candidates is not yet available.

Other issues that may impede expeditious transplantation in all intestinal transplant candidates include donor/recipient size incompatibility and cytomegalovirus (CMV) status. Most candidates for intestinal transplant have had massive bowel resections, and consequently there is a significant reduction in the capacity of their peritoneal cavity. Therefore, they often require donors who are 50%-75% smaller, thereby limiting the field of potential donors. This is extremely problematic in infants, as emphasized by the fact that in 1998 and 1999, the majority of the deaths on the intestine/liver waiting list (66%) occurred in candidates <6 years old.¹⁹⁹ In some situations, the donor/recipient size issue can be managed by surgical resection of segments of bowel and/or liver from grafts that would otherwise be too large.²⁰⁰ Because CMV enteritis is a significant problem posttransplant, many centers avoid using CMV positive donors in CMV negative recipients,²⁰² which can also exclude many potential donors.

Outcomes of patients undergoing intestinal transplantation 

The world experience 

There are no randomized trials comparing intestinal transplantation to long-term TPN or alternative forms of therapy. Data on the results of intestinal transplants are available from 3 sources: (1) The International Intestinal Transplant Registry (ITR), (2) UNOS database, and (3) reports from individual centers (Table 4). UNOS has collected both recipient and donor data for intestinal transplants performed since 1990. This data was compiled and published for the first time in 2001, and represents the United States' experience up to September 5, 2000 (Table 7).¹⁹⁶Data submission to the UNOS registry is mandatory for all accredited transplant centers. Based on UNOS data, the number of isolated intestine transplants performed in the United States has increased steadily since 1996. In 1999, there were 36 isolated intestine, 20 intestine/liver, and 12 multivisceral (with intestine included) transplants performed. The primary diagnoses in these recipients were SBS in 64%, functional bowel problems in 26%, graft failure (retransplant) in 6%, and other in 4%.

Table 7. Intestinal Transplant Results

Acute rejection, % of transplant recipients experiencing an acute rejection episode; CMV, % of transplant recipients experiencing a cytomegalovirus infection; PTLD, % of transplant recipients experiencing a post-transplant lymphoproliferative disorder; SB, small bowel only transplant; SB/liver, combined small bowel and liver transplant; MV, multivisceral transplant.

Data summarizing the world experience with intestinal transplantation is maintained in an international registry based in London, Canada, that is updated every 2 years. A summary of this data has previously been published twice (most recently in 1999).²⁰¹ This report can be reviewed on the ITR Web site (www.lhsc.on.ca/itr). Because intestinal transplants are performed in relatively small numbers at very few academic transplant centers around the world, it is likely that this registry data represents most, if not all, of the intestinal transplants performed worldwide since 1985. At the time of its last update in 1999, 474 intestinal transplants had been performed on 446 patients at 46 different centers in 16 different countries. This total includes intestine only transplants (216, 45%), combined intestine/liver transplants (186, 40%), and multivisceral (intestine, liver, pancreas, stomach, etc.) transplants (72, 15%). The majority of transplants have been performed in patients <16 years old (62%) (Table 7).

In patients with ESLD related to TPN, a combined intestine/liver transplant may be the only option for continued survival. In patients who will require TPN permanently, transplantation of the liver alone has generally resulted in recurrence of ESLD and a poor outcome. However, in carefully selected ESLD patients with significant residual intestine who are very likely to be weaned from TPN soon after transplant, successful transplantation of the liver alone can be achieved.²⁰³ Conversely, in the setting of ESLD, an isolated intestinal transplant is likely to yield poor results, although outcomes data stratifying isolated intestine transplant recipients based on their pretransplant liver abnormalities do not exist. It is not yet clear when the hepatic pathological process has become irreversible, or if more benign hepatic changes can be distinguished from those that will ultimately progress to ESLD. While it is generally acknowledged that a combined intestine/liver transplant is necessary if cirrhosis or portal hypertension are present, with potentially reversible lesions, such as cholestasis, an isolated intestinal transplant has been successful in some circumstances.²⁰⁴ Intestinal failure patients who progress to ESLD and are placed on the waiting list for a combined intestine/liver transplant have an extremely high mortality that exceeds that seen on all other solid organ transplant waiting lists, including liver only transplants (see below).

Patient and graft survival 

In the most recent UNOS cohort evaluated (1997 to 1998), the 1 year patient and graft survivals were 79% and 64%, respectively for intestine only transplants, and 50% and 49% in intestine/liver recipients, respectively. With long-term analysis, patient and graft survivals after intestine only transplants were 62% and 49% at 3 years, and 50% and 38% at 5 years, respectively. Long-term patient and graft survivals after combined intestine/liver transplants were 43% and 41% at 3 years, and 37% and 36% at 5 years, respectively.¹⁹⁶

Overall patient and graft survivals in patients transplanted after 1995 were 65% and 57% at 1 year, and 50% and 40% at 4 years. These results indicate a statistically significant improvement in graft (P = 0.02), but not patient (P = 0.46), survival from earlier cohorts. In all cohorts, the highest patient mortality occurs in the first 6 months posttransplant. This high incidence of early mortality was also noted in individual reports from the most experienced centers.²⁰⁵, ²⁰⁶, ²⁰⁷, ²⁰⁸ Patient (P = 0.001) and graft (P = 0.002) survival at 1 and 5 years were superior at centers that had performed >10 transplants in the ITR data, although this was not supported by the UNOS registry data.¹⁹⁶ Overall, these results suggest that the increasing experience with intestinal transplants contributes to improved results. Patient (P = 0.02), but not graft (P = 0.32), survival was significantly better in intestine only transplants compared with transplants involving additional organs (Table 8).

Table 8. Intestinal Transplant Registry Data Indicating Influence of Multiple Organ Transplants on Graft and Patient Survival in Intestinal Transplant Recipients

This likely reflects the higher pretransplant acuity of the patients who also need livers, the greater magnitude of the surgery they undergo, and the inability to remove their transplanted organs as a life-saving maneuver if there is uncontrolled rejection or sepsis posttransplant.

Living donors have been utilized in a small number of intestinal transplants performed to date. Living donors enhance the opportunity to minimize ischemic time and optimize donor recipient HLA matching. Furthermore, living donors eliminate the need to wait, which can be associated with high mortality in intestinal transplant candidates. The ITR data found no differences in graft survival between recipients of cadaver and living donor intestinal grafts. Although early evidence suggests that use of HLA-matched living donors may be associated with less rejection and fewer infectious complications,²⁰⁴ more data will be needed before this approach achieves wide acceptance.

Posttransplant complications 

Posttransplant complications associated with intestinal transplantation include acute rejection, chronic rejection, CMV infection, and posttransplant lymphoproliferative disease (PTLD).²⁰¹ For intestine only, intestine/liver, and multivisceral transplants, acute rejection occurred in 79%, 71%, and 56%, respectively; chronic rejection in 13%, 3%, and 0%, respectively, CMV infection in 24%, 18%, and 40%, respectively; and PTLD in 7%, 11%, and 13%, respectively. While not yet statistically significant, this data suggests that transplanting additional organs reduces rejection, but increases viral-associated complications.

Patient deaths were attributed to sepsis or multiorgan failure (69%), lymphoma (14%), ischemia/bleeding (13%), and rejection (12%). In surviving patients, 78% had full graft function, 10% had partial function, and 12% had their grafts removed. The most common indication for graft removal was rejection (57%), followed by ischemia/bleeding (23%), sepsis (6%), multiorgan failure (2%), lymphoma (1%), and other (10%).

Quality of life in home TPN patients and intestinal transplant recipients 

The quality of life associated with long-term TPN use has been evaluated by different investigators who have reached different conclusions.²⁰⁹, ²¹⁰ However, these investigators did not perform subgroup analysis of those patients with SBS. There are very few quality of life comparisons between intestinal failure patients who remain on TPN and those who undergo intestinal transplantation. Retrospective comparisons between small groups of intestinal transplant patients and long-term TPN patients matched for age and duration of illness suggest that quality of life is the same or slightly better with transplantation.²¹¹

Financial concerns of home parenteral nutrition and intestinal transplantation 

Financial issues must also be considered in managing intestinal failure patients. Today, provision of basic home parenteral nutrition (HPN) is associated with charges of between $250 and $500 per day for a given patient, although actual costs for TPN, including the pharmacist's time for compounding, are on the order of $18-$22 per day, excluding the additional charges of home care services, monitoring, and management of complications. Therefore, if administered 5 days/week, HPN charges often exceed $150,000/year, although costs are significantly less. The costs for transplant evaluation, the transplant and postoperative care, and posttransplant follow-up are not currently available for comparison.

Patients with SBS can lead a productive, lengthy, happy, and a useful life if educated and managed appropriately. It is possible to reduce or even eliminate TPN requirements over time in many of these patients using the evidence-based techniques of dietary and fluid management described in this report. Hormonal therapy may eventually be available to augment the intestinal adaptation process as this becomes better understood. For patients that do require TPN, it is essential the therapy be prescribed appropriately. In addition, TPN is associated with several potentially serious complications, many of which can be prevented when both the patient and the caring professional have the appropriate expertise.

There are limited indications for small intestinal transplantation. Eminent liver failure is currently the most appropriate indication, although as survival of both patient and graft continue to improve, these indications may be broadened. The management of these patients is complex and is undergoing constant evolution.

Back to Article Outline

References 

1. Crenn P, Haniche M, Valleur P, Hautefeuille P, Rambaud JC, Messing B. Surgical versus radiological evaluation of remaining small bowel length in short bowel syndrome (abstr). Gastroenterology. 1996;110:A321
   • View In Article
2. Bryant J. Observations upon the growth and length of the human intestine. Am J Med Sci. 1924;167:499–520
   • View In Article
   • CrossRef
3. Slater G, Aufses AH. Small-bowel length in Crohn's disease. Am J Gastroenterol. 1991;8:1037–1040
   • View In Article
4. Fanucci A, Cerro P, Fraracci L, Letto F. Small-bowel length measured by radiology. Gastrointestinal Radiol. 1984;9:349–351
   • View In Article
5. Nightingale JMD, Bartram CI, Lennard-Jones JE. Length of residual small bowel after partial resection: correlation between radiographic and surgical measurements. Gastrointestinal Radiol. 1991;16:305–306
   • View In Article
6. Messing B, Crenn P, Beau P, Boutron-Ruault MC, Rambaud JC, Matuchausky C. Long-term survival and parenteral nutrition dependence in adult patients with short bowel syndrome. Gastroenterology. 1999;117:1043–1050
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (145 KB)
   • CrossRef
7. Carbonnel F, Cosnes J, Chevret , Beaugerie L, Ngo Y, Malafosse M, et al. The role of anatomic factors in nutritional autonomy after extensive small bowel resection. JPEN. 1996;20:275–280
   • View In Article
8. Nightingale JMD, Lennard-Jones JE, Gertner DJ, Wood SR, Bartran CI. Colonic preservation reduces need for parenteral therapy, increases incidence of renal stones, but does not change high prevalence of gallstones in patients with a short bowel. Gut. 1992;33:1493–1497
   • View In Article
   • MEDLINE
   • CrossRef
9. 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
   • View In Article
   • MEDLINE
10. Florent C, Flourie B, Leblond A, Rautureau M, Bernier JJ, Rambaud JC. Influence of chronic lactulose ingestion on the colonic metabolism of lactulose in man (an in vivo study). J Clin Invest. 1985;75:608–613
    • View In Article
    • MEDLINE
    • CrossRef
11. Mughal M, Irving M. Home parenteral nutrition in the United Kingdom and Ireland. Lancet. 1986;200:383–386
    • View In Article
    • CrossRef
12. Van Gossum A, Espen-Han Group . Home parenteral nutrition (HPN) in adults: a multicentre survey in Europe in 1993. Clin Nutr. 1996;15:53–58
    • View In Article
    • Abstract
    • Full-Text PDF (1222 KB)
    • CrossRef
13. Van Gossum A, Colomb V, Hebuterne X, et al.  Home parenteral nutrition (HPN) in children: a multicentre study in Europe in 1997. Clin Nutr. 1998;17:42; (abstr)
    • View In Article
    • Full-Text PDF (137 KB)
    • CrossRef
14. Van Gossum A, Bakker H, Bozetti F, Staun M, Leon-Sanz M, Hebuterne X, et al. Home parenteral nutrition in adults: a European multicentre study in 1997. Clin Nutr. 1999;18:135–140
    • View In Article
    • Abstract
    • Full-Text PDF (866 KB)
    • CrossRef
15. Oley Foundation . North American home parenteral and enteral nutrition patient registry annual report. 1994;
    • View In Article
16. Georgeson LE, Breaux CW. Outcome and intestinal adaptation in neonatal short-bowel syndrome. J Pediatr Surg. 1992;27:344–350
    • View In Article
    • Abstract
    • CrossRef
17. Nightingale JMD, Lennard-Jones JE, Walker ER, Farthing MJ. Jejunal efflux in short bowel syndrome. Lancet. 1990;336:765–768
    • View In Article
    • Abstract
    • CrossRef
18. Woolf GM, Miller C, Kurian R, Jeejeebhoy KN. Nutritional absorption in short bowel syndrome. Dig Dis Sci. 1987;32:8–15
    • View In Article
    • MEDLINE
    • CrossRef
19. Langefoged K, Olgaard K. Fluid and electrolyte absorption and renin-angiotensin-aldosterone axis in patients with severe short-bowel syndrome. Gastroenterology. 1979;14:729–735
    • View In Article
20. Solhaug JH, Tvete S. Adaptive changes in the small intestine following bypass operation for obesity. Scand J Gastroenterol. 1978;13:401–408
    • View In Article
    • MEDLINE
    • CrossRef
21. Doldi SB. Intestinal adaptation following jejuno-ileal bypass. Clin Nutr. 1991;10:138–145
    • View In Article
    • MEDLINE
    • CrossRef
22. Dowling RH, Booth CC. Functional compensation after small-bowel resection in man. Lancet. 1966;2:146–147
    • View In Article
    • MEDLINE
23. Weinstein LD, Shoemaker CP, Hersh T, Wright HK. Enhanced intestinal absorption after small bowel resection in man. Arch Surg. 1968;99:560–561
    • View In Article
    • MEDLINE
24. Kurkchubasche AG, Rowe MI, Smith SD. Adaptation in short-bowel syndrome: reassessing old limits. J Pediatr Surg. 1993;28:1069–1071
    • View In Article
    • Abstract
    • CrossRef
25. Joyeux H, Gouttebel MC, Briand D, Saint-Aubert B, Matias J. Short bowel syndromes in adults, prognostic factors, evaluation, and treatment. Retrospective study, apropos of 80 cases. Chirurgie. 1994-1995;120:187–193 [French]
    • View In Article
    • MEDLINE
26. Kaufman SS, Loseke CA, Lupo JV, Young RJ, Murray ND, Vanderhoof JA. Factors affecting duration of parenteral hyperalimentation in children with short bowel syndrome. Gastroenterology. 1996;110:A809; (abstr)
    • View In Article
27. Sham J, Martin G, Meddings JB, Sigalet DL. Epidermal growth factor improves nutritional outcome in a rat model of short bowel syndrome. J Pediatric Surg. 2002;37:765–769
    • View In Article
28. Gracy M. The contaminated small bowel syndrome: pathogenesis, diagnosis, and treatment. Am J Clin Nutr. 1979;32:234–243
    • View In Article
    • MEDLINE
29. Nightingale JMD, Kamm MA, van der Sijp JRM, Morris GP, Walker ER, Mather SJ, et al. Disturbed gastric emptying in the short bowel syndrome. Evidence for a colonic brake. Gut. 1993;34:1171–1176
    • View In Article
    • MEDLINE
    • CrossRef
30. Nightingale JMD, Kamm MA, van der Sijp JRM. Gastrointestinal hormones in short bowel syndrome. Peptide YY may be the colonic brake to gastric emptying. Gut. 1996;39:267–272
    • View In Article
    • MEDLINE
    • CrossRef
31. Ameen VZ, Powell GK, Jones LA. Quantitation of fecal carbohydrate excretion in patients with short bowel syndrome. Gastroenterology. 1987;92:493–500
    • View In Article
    • Abstract
    • Full-Text PDF (863 KB)
32. McIntyre PB, Fitchew M, Lennard-Jones JE. Patients with a high jejunostomy do not need a special diet. Gastroenterology. 1986;91:25–33
    • View In Article
    • Abstract
    • Full-Text PDF (835 KB)
33. Levy E, Frileux P, Sandrucci S, Ollivier JM, Masini JP, Cosnes J, et al. Continuous enteral nutrition during the early adaptive stage of the short bowel syndrome. Br J Surg. 1988;75:549–553
    • View In Article
    • MEDLINE
    • CrossRef
34. Cosnes J, Evard D, Beaugerie L, Gendre JP, Le Quintrec Y. Improvement in protein absorption with a small peptide-base diet in patients with high jejunostomy. Nutrition. 1992;8:406–411
    • View In Article
    • MEDLINE
35. Windmueller HG, Spaeth AE. Identification of ketone bodies and glutamine as the major respiratory fuels in vivo for postabsorptive rat small intestine. J Biol Chem. 1978;253:69–76
    • View In Article
    • MEDLINE
36. Guarino A, Canani RB, Iafusco M, Casola A, Russo R, Rubino A. In vivo and in vitro effects of human growth hormone on rat intestine ion transport. Pediatr Res. 1995;37:576–580
    • View In Article
    • MEDLINE
    • CrossRef
37. Souba W, Klimberg S, Plumley D, Salloum RM, Flynn TC, Bland KI, et al. The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection. J Surg Res. 1990;48:383–391
    • View In Article
    • MEDLINE
    • CrossRef
38. Byrne TA, Morrissey TB, Nattakom TV, Ziegler TR, Wilmore DW. Growth hormone, glutamine, and a modified diet enhance nutrient absorption in patients with severe short bowel syndrome. JPEN. 1995;19:296–302
    • View In Article
39. Scolapio JS, Camilleri M, Fleming CR, Oenning LV, Burton DD, Sebo TJ, et al. Effect of growth hormone, glutamine, and diet on adaptation in short-bowel syndrome: a randomized, controlled trial. Gastroenterology. 1997;113:1074–1081
    • View In Article
    • Abstract
    • Full-Text PDF (307 KB)
    • CrossRef
40. Szkudlarek J, Jeppesen PB, Mortensen PB. Effect of high dose growth hormone with glutamine and no change in diet on intestinal absorption in short bowel patients: a randomized, double blind, crossover, placebo controlled study. Gut. 2000;47:199–205
    • View In Article
    • MEDLINE
    • CrossRef
41. Beaugerie L, Carbonnel F, Hecketsweiler B, Dechelotte P, Gendre JP, Cosnes J. Effects of an isotonic oral rehydration solution, enriched with glutamine, on fluid and sodium absorption in patients with a short-bowel. Aliment Pharmacol Ther. 1997;11:741–746
    • View In Article
    • MEDLINE
42. Ruppin H, Bar-Meir S, Soergel KH, Wood CM, Schmitt MG. Absorption of short-chain fatty acids by the colon. Gastroenterology. 1980;78:1500–1507
    • View In Article
    • Abstract
43. Scolapio JS. Effect of growth hormone, glutamine, and diet on body composition in short bowel syndrome: a randomized, controlled trial. JPEN. 1999;23:309–312
    • View In Article
44. Ohkohchi N, Andoh T, Izumi U, Igarashi Y, Ohi R. Disorder of bile acid metabolism in children with short bowel syndrome. J Gastroenterol. 1997;32:472–479
    • View In Article
    • MEDLINE
    • CrossRef
45. Little KH, Schiller LR, Bilhartz LE, Fortran JS. Treatment of severe steatorrhea with ox bile in an ileectomy patient with residual colon. Dig Dis Sci. 1992;37:929–933
    • View In Article
    • MEDLINE
    • CrossRef
46. Fordtran JS, Bunch F, Davis GR. Ox bile treatment of severe steatorrhea in an ileectomy-ileostomy patient. Gastroenterology. 1982;82:564–567
    • View In Article
    • Abstract
47. Djurdjevic D, Popovic O, Necic D, Hranisavljevic S. Ox bile treatment of severe steatorrhea in a colectomy and ileectomy patient (letter). Gastroenterology. 1988;95:1160
    • View In Article
    • Full-Text PDF (142 KB)
48. Heydorn S, Jeppesen PB, Mortensen PB. Bile acid replacement therapy with cholylsarcosine for short-bowel syndrome. Scand J Gastroenterol. 1999;34:818–823
    • View In Article
    • MEDLINE
    • CrossRef
49. Hoffman AF, Poley R. Role of bile acid malabsorption in pathogenesis of diarrhea and steatorrhea in patients with ileal resection. Gastroenterology. 1972;62:918–934
    • View In Article
50. Woolf GM, Miller C, Kurian R, Jeejeebhoy KN. Diet for patients with a short bowel: high fat or high carbohydrate?. Gastroenterology. 1983;84:823–828
    • View In Article
    • Abstract
    • Full-Text PDF (638 KB)
51. Jeppesen PB, Mortensen PB. The influence of a preserved colon on the absorption of medium chain fat in patients with small bowel resection. Gut. 1998;43:478–483
    • View In Article
    • MEDLINE
    • CrossRef
52. Marteau P, Messing B, Arrigoni E, Briet F, Flourie B, Morin MC, et al. Do patients with short-bowel syndrome need a lactose-free diet?. Nutrition. 1997;13:13–16
    • View In Article
    • Abstract
    • Full-Text PDF (482 KB)
    • CrossRef
53. Arrigoni E, Marteau P, Briet F, Pochart P, Rambaud JC, Messing B. Tolerance and absorption of lactose from milk and yogurt during short-bowel syndrome in humans. Am J Clin Nutr. 1994;60:926–929
    • View In Article
    • MEDLINE
54. Englyst HN, Trowell H, Southgate DAT, Cummings JH. Dietary fibre and resistant starch. Ann J Clin Nutr. 1987;46:873–874
    • View In Article
55. Bond JH, Currier BE, Buchwald H, Levitt MD. Colonic conservation of malabsorbed carbohydrate. Gastroenterology. 1980;78:444–447
    • View In Article
    • Abstract
    • Full-Text PDF (479 KB)
56. Cummings JH, Gibson GR, Macfarlane GT. Quantitative estimates of fermentation in the hind gut of man. Acta Vet Scand Supp. 1989;86:76–82
    • View In Article
57. Nordgaard I, Hansen BS, Mortensen PB. Colon as a digestive organ in patients with short bowel. Lancet. 1994;343:373–376
    • View In Article
    • Abstract
    • CrossRef
58. Briet F, Flourie B, Achour L, et al.  Bacterial adaptation in patients with short bowel and colon in continuity. Gastroenterology. 1995;109:1446–1453
    • View In Article
    • Abstract
    • Full-Text PDF (843 KB)
    • CrossRef
59. Alloju M, Ehrinpreis MN. Shortage of intravenous multivitamin solution in the United States. N Engl J Med. 1997;337:54–55
    • View In Article
    • MEDLINE
    • CrossRef
60. Schiano TD, Klang MG, Quesada E, et al.  Thiamine status in patients receiving long-term home parenteral nutrition. Am J Gastroenterol. 1996;91:2555–2559
    • View In Article
    • MEDLINE
61. Mock DM, DeLorimer AA, Liebman WM, et al.  Biotin deficiency: an unusual complication of parenteral alimentation. N Engl J Med. 1981;304:820–824
    • View In Article
    • MEDLINE
    • CrossRef
62. Anderson H, Bosaeus I, Brummer RJ, et al.  Nutritional and metabolic consequences of extensive bowel resection. Dig Dis. 1986;4:193–202
    • View In Article
    • MEDLINE
    • CrossRef
63. Denburg J, Bensen W, Ali MA, et al.  Megaloblastic anemia in patients receiving total parenteral nutrition without folic aid or vitamin B12 supplementation. Can Med Assoc J. 1977;117:144–146
    • View In Article
    • MEDLINE
64. Edes TE, Walk BE, Thorton WH, Fritsche KL. Essential fatty acid sufficiency does not preclude fat-soluble-vitamin deficiency in short-bowel syndrome. Am J Clin Nutr. 1991;53:499–502
    • View In Article
    • MEDLINE
65. Compston JE, Horton LWL. Oral 25-hydroxyvitamin D₃ in treatment of osteomalacia associated with ileal resection and cholestyramine. Gastroenterology. 1978;74:900–902
    • View In Article
    • Abstract
    • Full-Text PDF (345 KB)
66. Mokete B, De Cock R. Xerophthalmia and short bowel syndrome. Br J Gastroenterol. 1998;82:1340–1341 (letter)
    • View In Article
67. Stamp TCB, Round JM. Seasonal changes in human plasma levels of 25-hydroxyvitamin D. Nature. 1974;247:563–565
    • View In Article
    • MEDLINE
    • CrossRef
68. Haddad JG, Hahn TJ. Natural and synthetic sources of 25-hydroxyvitamin D in man. Nature. 1973;244:515–517
    • View In Article
    • MEDLINE
    • CrossRef
69. Selby PL, Peacock M, Bambach CP. Hypomagnesaemia after small bowel resection: treatment with 1α-hydroxylated vitamin D metabolites. Br J Surg. 1984;71:334–337
    • View In Article
    • MEDLINE
    • CrossRef
70. Fritsma GA. Vitamin E and autooxidation. Am J Med Technol. 1983;49:453–456
    • View In Article
    • MEDLINE
71. Howard L, Ovesen L, Sataya-Murti S, Chu R. Reversible neurological symptoms caused by vitamin E deficiency in a patient with short bowel syndrome. Am J Clin Nutr. 1982;36:1243–1249
    • View In Article
    • MEDLINE
72. Meydani M, Cohn JS, Macauley JB, et al.  Postprandial changes in the plasma concentration of alpha and gamma tocopherol in human subjects fed a fat-rich meal supplemented with fat soluble vitamins. J Nutr. 1989;119:1252–1258
    • View In Article
    • MEDLINE
73. Thurnham DI, Davies JA, Crump BJ, et al.  The use of different lipids to express serum tocopherol: lipid ratios for the measurement of vitamin E status. Ann Clin Biochem. 1986;23:514–520
    • View In Article
74. Conly JM, Stein K, Worobetz L, et al.  The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. Am J Gastroenterol. 1994;89:915–923
    • View In Article
    • MEDLINE
75. Wolman SL, Anderson GH, Marliss EB, Jeejeebhoy KN. Zinc in total parenteral nutrition: requirements and metabolic effects. Gastroenterology. 1979;76:458–467
    • View In Article
    • MEDLINE
76. Prasad AS. Zinc in growth and development and spectrum of human zinc deficiency. J Am Coll Nutr. 1988;7:377–384
    • View In Article
    • MEDLINE
77. Golden MNH, Golden BE, Jackson AA. Skin breakdown in kwashiorkor responds to zinc. Lancet. 1980;1:1256
    • View In Article
    • MEDLINE
78. Golden MNH, Golden BE, Harland PSEG, Jackson AA. Zinc and immunocompetence in protein-energy malnutrition. Lancet. 1978;1:1226–1227
    • View In Article
    • MEDLINE
79. Prasad AS. Laboratory diagnosis of zinc deficiency. J Am Coll Nutr. 1985;4:591–598
    • View In Article
    • MEDLINE
80. Fleming CR, Lie JT, McCall JT, et al.  Selenium deficiency and fatal cardiomyopathy in a patient on home parenteral nutrition. Gastroenterology. 1982;83:689–693
    • View In Article
    • Abstract
81. Brown M, Cohen HJ, Lyons JM, et al.  Proximal muscle weakness and selenium deficiency associated with long-term parenteral nutrition. Am J Clin Nutr. 1986;43:549–554
    • View In Article
    • MEDLINE
82. Vinton NE, Dahlstrom KA, Strobel CT, Ament ME. Macrocytosis and pseudoalbinism: manifestations of selenium deficiency. J Pediatr. 1987;111:711–717
    • View In Article
    • Abstract
    • Full-Text PDF (1716 KB)
    • CrossRef
83. Jeejeebhoy KN, Chu RC, Marliss EB, et al.  Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition. Am J Clin Nutr. 1977;30:531–538
    • View In Article
    • MEDLINE
84. Roginski EE, Mertz W. Effects of chromium (III) supplementation on glucose and amino acid metabolism in rats fed a low protein diet. J Nutr. 1969;97:525–530
    • View In Article
    • MEDLINE
85. Moukarzel A, Song MK, Buchman AL, et al.  Excessive chromium intake in children receiving total parenteral nutrition. Lancet. 1992;339:385–388
    • View In Article
    • Abstract
    • CrossRef
86. Williams DM. Copper deficiency in humans. Semin Hematol. 1983;20:118–128
    • View In Article
    • MEDLINE
87. McFadden MA, Delegge MH, Kirby DF. Medication delivery in the short-bowel syndrome. JPEN. 1993;17:180–186
    • View In Article
88. Windsor CWO, Fejfar J, Woodward DAK. Gastric secretion after massive small bowel resection. Gut. 1969;10:779–786
    • View In Article
    • MEDLINE
    • CrossRef
89. Williams NS, Evans P, King RFGJ. Gastric acid secretion and gastrin production in the short bowel syndrome. Gut. 1985;26:914–919
    • View In Article
    • MEDLINE
    • CrossRef
90. Windsor CWO, Fejfar J, Woodward DAK. Gastric secretion after massive small bowel resection. Gut. 1969;10:779–786
    • View In Article
    • MEDLINE
    • CrossRef
91. Nightingale JMD, Lennard-Jones JE, Walker ER, Farthing MJG. Jejunal efflux in short bowel syndrome. Lancet. 1990;336:765–768
    • View In Article
    • Abstract
    • CrossRef
92. Jacobsen K, Ladefoged K, Stage JG, Jarnum S. Effects of cimetidine on jejunostomy effluents in patients with severe short bowel syndrome. Scand J Gastroenterol. 1986;21:824–828
    • View In Article
    • MEDLINE
    • CrossRef
93. Nightingale JMD, Walker ER, Farthing MJG, Lennard-Jones JE. Effect of omeprazole on intestinal output in the short bowel syndrome. Aliment Pharmacol Ther. 1991;5:405–412
    • View In Article
    • MEDLINE
    • CrossRef
94. Jeppesen PB, Staun M, Tjellesen L, Mortensen PB. Effect of intravenous ranitidine and omeprazole on intestinal absorption of water, sodium, and macronutrients in patients with intestinal resection. Gut. 1998;43:763–769
    • View In Article
    • MEDLINE
    • CrossRef
95. Cooper JC, Williams NS, King RF, et al.  Effects of a long-acting somatostatin analogue in patients with severe ileostomy diarrhea. Br J Surg. 1986;73:128–131
    • View In Article
    • MEDLINE
    • CrossRef
96. Ladefofed K, Christensen KC, Hegnhoj J, Jarnum S. Effect of a long-acting somatostatin analogue SMS 201-995 on jejunostomy effluents in patients with severe short bowel syndrome. Gut. 1989;30:943–949
    • View In Article
    • MEDLINE
    • CrossRef
97. O'Keefe SJD, Haymond MW, Bennet WM, et al.  Long-acting somatostatin analogue therapy and protein metabolism in patients with jejunostomies. Gastroenterology. 1994;107:379–388
    • View In Article
    • Abstract
    • Full-Text PDF (1084 KB)
98. Niv Y, Charash B, Sperber AD, Oren M. Effect of octreotide on gastrostomy, duodenostomy, and cholecystostomy effluents: a physiologic study of fluid and electrolyte balance. Am J Gastroenterol. 1997;92:2107–2111
    • View In Article
    • MEDLINE
99. Catnach SM, Anderson JV, Fairclough PD, et al.  Effect of octreotide on gall stone prevalence and gall bladder motility in acromegaly. Gut. 1993;34:270–273
    • View In Article
    • MEDLINE
    • CrossRef
100. Roslyn JJ, Pitt HA, Mann LL, Ament ME, DenBesten L. Gallbladder disease in patients on long-term parenteral nutrition. Gastroenterology. 1983;84:148–154
     • View In Article
     • Abstract
101. Fortran JS. Stimulation of active and passive sodium absorption by sugars in the human jejunum. J Clin Invest. 1975;55:728–737
     • View In Article
     • MEDLINE
     • CrossRef
102. Treatment and prevention of dehydration in diarrhea diseases: a guide for use at the primary level. WHO: Geneva; 1976;
     • View In Article
103. Pfeiffer A, Schmidt T, Kaess H. The role of osmolality in the absorption of a nutrient solution. Aliment Pharmacol Ther. 1998;12:281–286
     • View In Article
     • MEDLINE
     • CrossRef
104. Fortran JS, Rector FC, Carter NW. The mechanism of sodium absorption in the human small intestine. J Clin Invest. 1968;47:884–900
     • View In Article
     • MEDLINE
     • CrossRef
105. Davis GR, Santa Ana CA, Morawski SG, Fortran JC. Permeability characteristics of human jejunum, ileum, proximal colon, and distal colon: results of potential difference measurements and unidirectional fluxes. Gastroenterology. 1982;83:844–850
     • View In Article
     • Abstract
106. Selby PL, Peacock M, Bambach CP. Hypomagnesemia after small bowel resection: treatment with 1α-hydroxylated vitamin D metabolites. Br J Surg. 1984;71:334–337
     • View In Article
     • MEDLINE
     • CrossRef
107. Fleming CR, George L, Stoner GL, Tarrosa VB, Moyer TP. The importance of urinary magnesium values in patients with gut failure. Mayo Clin Proc. 1996;71:21–24
     • View In Article
     • Abstract
     • Full Text
     • Full-Text PDF (3930 KB)
     • CrossRef
108. Anast CS, Winnacker JL, Forte LR, Burns TW. Impaired release of parathyroid hormone in magnesium deficiency. Clin Endocrinol Metab. 1976;42:707–717
     • View In Article
109. Hylander E, Ladefoged K, Madsen S. Calcium balance and bone mineral content following small-intestinal resection. Scand J Gastroenterol. 1981;16:167–176
     • View In Article
     • MEDLINE
     • CrossRef
110. Scolapio JS, Tammela L, Stoner G. Injectible magnesium, given orally: attempt at magnesium replacement in short bowel syndrome. Gastroenterology. 1999;116:A576; (abstr)
     • View In Article
111. Jeppesen PB, Hartmann B, Hansen BS, et al.  Impaired meal stimulated glucagon-like peptide 2 response in ileal resected short bowel patients with intestinal failure. Gut. 1999;45:559–563
     • View In Article
     • MEDLINE
     • CrossRef
112. Porus RL. Epithelial hyperplasia following massive small bowel resection in man. Gastroenterology. 1965;48:753–757
     • View In Article
     • MEDLINE
113. O'Keefe SJD, Shorter RG, Bennett WM, Haymond MW. Villous hyperplasia is uncommon in patients with massive intestinal resection. Gastroenterology. 1992;102:A231; (abstr)
     • View In Article
114. Jeppesen PB, Hartmann B, Thulesen J, Graff J, Lohmann J, Hansen BS, et al. Glucagon-like peptide 2 improves nutrient absorption in short-bowel patients with no colon. Gastroenterology. 2001;120:806–815
     • View In Article
     • Abstract
     • Full Text
     • Full-Text PDF (230 KB)
     • CrossRef
115. Ellegard L, Bosaeus I, Nordgren S, Bengtsson BA. Low-dose recombinant human growth hormone increases body weight and lean body mass in patients with short bowel syndrome. Ann Surg. 1997;225:88–96
     • View In Article
     • MEDLINE
     • CrossRef
116. Dobbins JW, Binder HJ. Effect of bile salts and fatty acids on the colonic absorption of oxalate. Gastroenterology. 1976;70:1096–1100
     • View In Article
     • Abstract
117. Barilla DE, Notz C, Kennedy D, Pak CYC. Renal oxalate excretion following oral oxalate loads in patients with ileal disease and with renal and absorptive hypercalciurias. Effect of calcium and magnesium. Am J Med. 1978;64:579–585
     • View In Article
     • Abstract
     • Full-Text PDF (863 KB)
     • CrossRef
118. Buchman AL, Moukarzel A, Ament ME. Excessive urinary oxalate excretion occurs in long term TPN patients both with and without ileostomies but is not associated with TPN-induced nephropathy. J Am Coll Nutr. 1995;14:24–28
     • View In Article
     • MEDLINE
119. Rockwell GF, Campfield T, Nelson BC, Uden PC. Oxalogenesis in parenteral nutrition solution components. Nutrition. 1999;14:836–839
     • View In Article
     • Abstract
     • Full Text
     • Full-Text PDF (56 KB)
     • CrossRef
120. Burke JF, Wolfe RR, Mullany CJ, Mathews DE, Bier DM. Glucose requirements following burn injury. Ann Surg. 1979;190:274–285
     • View In Article
     • MEDLINE
     • CrossRef
121. Buchman AL, Moukarzel A, Goodson B, Herzog F, Pollack P, Reyen L, et al. Catheter-related infections associated with home parenteral nutrition and predictive factors for the need for catheter removal in their treatment. JPEN. 1994;18:297–302
     • View In Article
122. Buchman AL, Goodson B, Herzog F, Ament ME. Catheter thrombosis and superior/inferior vena cava syndrome are rare complications of long-term parenteral nutrition. Clin Nutr. 1994;13:356–360
     • View In Article
     • MEDLINE
     • CrossRef
123. Buchman AL. Complications of long-term home total parenteral nutrition: their identification, prevention and treatment. Dig Dis Sci. 2001;46:1–18
     • View In Article
     • MEDLINE
     • CrossRef
124. Buchman AL. Handbook of nutritional support. Baltimore: Williams and Wilkins; 1997;
     • View In Article
125. Buchman AL, Ament ME. Fifteen-year survival of a Broviac catheter used for home parenteral nutrition. JPEN J Parenter Enteral Nutr. 1993;17:489
     • View In Article
     • MEDLINE
126. Scolapio JS, Fleming CR, Kelly DG, et al.  Survival of home parenteral nutrition-treated patients: 20 years of experience at the Mayo Clinic. Mayo Clin Proc. 1999;74:217–222
     • View In Article
     • Abstract
     • Full Text
     • Full-Text PDF (5422 KB)
     • CrossRef
127. Stanko RT, Nathan G, Mendelow H, Adibi SA. Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. Gastroenterology. 1987;92:197–202
     • View In Article
     • Abstract
     • Full-Text PDF (924 KB)
128. Bowyer BA, Fleming CR, Ludwig J, Petz K, McGill DB. Does long-term parenteral nutrition in adult patients cause chronic liver disease?. JPEN J Parenter Enteral Nutr. 1985;9:11–17
     • View In Article
     • MEDLINE
129. Buchman AL, Ament ME. Liver disease and total parenteral nutrition. In:  Zakim TD, Boyer  editor. Textbook of hepatology. Philadelphia: Saunders; 1996;p. 1810–1821
     • View In Article
130. Briones ER, Iber FL. Liver and biliary tract changes associated with total parenteral nutrition: pathogenesis and prevention. J Am Coll Nutr. 1995;14:219–228
     • View In Article
     • MEDLINE
131. Cavicchi M, Beau P, Crenn P, Degott C, Messing B. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med. 2000;132:525–532
     • View In Article
     • MEDLINE
132. Kelly DA. Liver complications of pediatric parenteral nutrition-epidemiology. Nutrition. 1998;14:153–157
     • View In Article
     • Abstract
     • Full Text
     • Full-Text PDF (52 KB)
     • CrossRef
133. Chan S, McCowen KC, Bistrian BR, Thibault A, Keane-Ellison M, Forse RA, et al. Incidence, prognosis, and etiology of end-stage liver disease in patients receiving home total parenteral nutrition. Surgery. 1999;126:28–34
     • View In Article
     • Abstract
     • Full Text
     • Full-Text PDF (41 KB)
     • CrossRef
134. Buchman AL, Dubin MD, Jenden D, Moukarzel A, Roch MH, Rice K, et al. Lecithin supplementation causes a decrease in hepatic steatosis in patients receiving long term parenteral nutrition. Gastroenterology. 1992;102:1363–1370
     • View In Article
     • Abstract
     • Full-Text PDF (985 KB)
135. Buchman AL, Dubin MD, Moukarzel AA, Jenden DJ, Roch M, Rice KM, et al. Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology. 1995;22:1399–1403
     • View In Article
     • MEDLINE
     • CrossRef
136. Buchman AL, Sohel M, Dubin M, Jenden DJ, Roch M. Choline deficiency causes reversible hepatic abnormalities in patients during parenteral nutrition: proof of a human choline requirement; a placebo-controlled trial. JPEN J Parenter Enteral Nutr. 2001;25:260–268
     • View In Article
     • MEDLINE
137. Spagnuolo MI, Iorio R, Vegnente A, Guarino A. Ursodeoxycholic acid for treatment of cholestasis in children on long-term total parenteral nutrition: a pilot study. Gastroenterology. 1996;111:716–719
     • View In Article
     • Abstract
     • Full-Text PDF (236 KB)
     • CrossRef
138. Lindor KD, Burnes J. Ursodeoxycholic acid for the treatment of home parenteral nutrition-associated cholestasis. Gastroenterology. 1991;101:250–253
     • View In Article
     • Abstract
     • Full-Text PDF (764 KB)
139. Lowry SF, Brennan MF. Abnormal liver function during parenteral nutrition: relation to infusion excess. J Surg Res. 1979;26:300
     • View In Article
     • CrossRef
140. Reif S, Tano M, Oliverio R, Young C, Rossi T. Total parenteral nutrition-induced steatosis: reversal by parenteral lipid infusion. JPEN. 1991;15:102–104
     • View In Article
141. Bowyer BA, Miles JM, Haymond MW, Fleming CR. L-carnitine therapy in home parenteral nutrition patients with abnormal liver tests and low plasma carnitine concentration. Gastroenterology. 1988;94:434–438
     • View In Article
     • Abstract
     • Full-Text PDF (525 KB)
142. Messing B, Bories C, Kunstlinger F, Bernier JJ. Does total parenteral nutrition induce gallbladder sludge formation and lithiasis?. Gastroenterology. 1983;84:1012–1019
     • View In Article
     • Abstract
     • Full-Text PDF (1108 KB)
143. Mashako MNK, Cezard JP, Boige N, Chayvialle JA, Bernard C, Navarro J. The effect of artificial feeding on cholestasis, gallbladder sludge and lithiasis in infants: correlation with plasma cholecystokinin levels. Clin Nutr. 1991;10:320–327
     • View In Article
     • MEDLINE
     • CrossRef
144. Pitt HA, King W, Mann LL. Increased risk of cholelithiasis with prolonged parenteral nutrition. Am J Surg. 1983;145:106–112
     • View In Article
     • MEDLINE
     • CrossRef
145. Pitt HA, Berquist WE, Mann LL, Porter-Finn V, Fonkalsrud EW, Ament ME, et al. Parenteral nutrition induces calcium bilirubinate gallstones. Gastroenterology. 1983;84:1274; (abstr)
     • View In Article
146. Ling PR, Sheikh M, Boyce P, Keane-Ellison M, Thibault A, Burke P, et al. Cholecystokinin (CCK) secretion in patients with severe short bowel syndrome (SSBS). Dig Dis Sci. 2001;46:859–864
     • View In Article
     • MEDLINE
     • CrossRef
147. Sitzman JV, Pitt HA, Steinborn PA, Pasha ZR, Sanders RC. Cholecystokinin prevents parenteral nutrition induced biliary sludge in humans. Surg Gynecol Obstet. 1990;170:25–31
     • View In Article
     • MEDLINE
148. Apelgren KN, Willard DA, Vargish T. TPN alters gallbladder responsitivity to cholecystokinin. JPEN J Parenter Enteral Nutr. 1988;12:11S; (abstr)
     • View In Article
149. From the Centers for Disease Control and Prevention . Lactic acidosis traced to thiamine deficiency related to nationwide shortage of multivitamins for total parenteral nutrition. United States. 1997;278:109–111
     • View In Article
150. Kitamura K, Yamaguchi T, Tanaka H, et al.  TPN-induced fulminant beriberi: a report on our experience and a review of the literature. Surg Today. 1996;26:769–776
     • View In Article
     • MEDLINE
     • CrossRef
151. Hudson M, Pocknee R, Mowat NAG. D-lactic acidosis in short bowel syndrome—an examination of possible mechanisms. Q J Med. 1990;74:157–163
     • View In Article
     • MEDLINE
152. Kadakia SC. D-lactic acidosis in a patient with jejunoileal bypass. J Clin Gastroenterol. 1995;20:154–156
     • View In Article
     • MEDLINE
     • CrossRef
153. Moukarzel AA, Haddad I, Ament ME, Buchman AL, Reyen L, Maggioni A, et al. 230 patient years of experience with home long-term parenteral nutrition in childhood: natural history and life of central venous catheters. J Pediatr Surg. 1994;29:1323–1327
     • View In Article
     • Abstract
     • CrossRef
154. Mailloux RJ, Delegge MH, Kirby DF. Pulmonary embolism as a complication of long-term total parenteral nutrition. JPEN. 1993;17:578–582
     • View In Article
155. Beers TR, Burnes J, Fleming CR. Superior vena caval obstruction in patients with gut failure receiving home parenteral nutrition. J Parenter Enteral Nutr. 1990;14:474–479
     • View In Article
156. Dollery CM, Sullivan ID, Bauraind O, Bull C, Milla PJ. Thrombosis and embolism in long-term central venous access for parenteral nutrition. Lancet. 1994;344:1043
     • View In Article
     • Abstract
     • CrossRef
157. Stine KC, Friedman HS, Kurtzberg J, Filston HC, Baker ME, Lowe J, et al. Pulmonary septic emboli mimicking metastatic rhabdomyosarcoma. J Pediatr Surg. 1989;24:491–493
     • View In Article
     • Abstract
     • Full-Text PDF (709 KB)
     • CrossRef
158. Hayden L, Stewart GR, Johnson DC, Fisher MM. Transthoracic right atrial cannulation for total parenteral nutrition—case report. Anaesth Intensive Care. 1981;9:53–57
     • View In Article
     • MEDLINE
159. Book WM, Raviele AA, Vincent RN. Transhepatic vascular access in pediatric cardiology patients with occlusion of traditional central venous sites. J Invasive Cardiol. 1999;11:341–344
     • View In Article
     • MEDLINE
160. Robertson LJ, Jaques PF, Mauro MA, Azizkhan RG, Robards J. Percutaneous inferior vena cava placement of tunneled silastic catheters for prolonged vascular access in infants. J Pediatr Surg. 1990;25:596–598
     • View In Article
     • Abstract
     • CrossRef
161. Buchman AL, Moukarzel AA, Ament ME, Gornbein ME, Goodson B, Carlson C, et al. Serious renal impairment is associated with long-term parenteral nutrition. J Parenter Enteral Nutr. 1993;17:438–444
     • View In Article
162. Buchman AL, Moukarzel AA. Metabolic bone disease associated with total parenteral nutrition. Clin Nutr. 2000;19:217–231
     • View In Article
     • Full-Text PDF (261 KB)
     • CrossRef
163. Buchman AL, Sohel M, Brown M, Jenden DJ, Ahn C, Roch M, et al. Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study. JPEN. 2001;25:30–35
     • View In Article
164. Idoate MA, Martinez AJ, Bueno J, Abu-Elmagd K, Reyes J. The neuropathology of intestinal failure and small bowel transplantation. Acta Neuropathol. 1999;97:502–508
     • View In Article
     • MEDLINE
     • CrossRef
165. Gibson LD, Carter R, Hinshaw DB. Segmental reversal of small intestine after massive bowel resection. JAMA. 1962;182:952–954
     • View In Article
     • MEDLINE
166. Thomas JF, Jordan GL, Houston GLJ. Massive resection of small bowel and total colectomy: use of reversed segment. Arch Surg. 1965;90:781–786
     • View In Article
     • MEDLINE
167. Shepard D. Antiperistaltic bowel segment in the treatment of the short bowel syndrome. Ann Surg. 1966;163:850–855
     • View In Article
     • MEDLINE
     • CrossRef
168. Venables CW, Ellis H, Smith AD. Antiperistaltic segments after massive intestinal resections. Lancet. 1966;2:1390–1394
     • View In Article
     • MEDLINE
169. Fink WJ, Olson JD. The massive bowel resection syndrome. Treatment with reversed intestinal segments. Arch Surg. 1967;94:700–706
     • View In Article
     • MEDLINE
170. Wilmore DW, Johnson CJ. Metabolic effects of small bowel reversal in treatment of the short bowel syndrome. Arch Surg. 1968;97:784–791
     • View In Article
     • MEDLINE
171. Poth EJ. Use of gastrointestinal reversal in surgical procedures. Am J Surg. 1969;118:893–899
     • View In Article
     • MEDLINE
     • CrossRef
172. Pertsemlidis D, Kark AE. Antiperistaltic segments for the treatment of short bowel syndrome. Am J Gastroenterol. 1974;62:526–530
     • View In Article
     • MEDLINE
173. Hakami M, Moslehy A, Mosavy SH. Reversed jejunal segment used to treat the short bowel syndrome. Am Surg. 1975;41:432–435
     • View In Article
     • MEDLINE
174. Pigot F, Messing B, Chaussade S, Pfeiffer A, Pouliquen X, Jian R. Severe short bowel syndrome with a surgically reversed small bowel segment. Dig Dis Sci. 1990;35:137–144
     • View In Article
     • MEDLINE
     • CrossRef
175. Panis Y, Messing B, Rivet P, Coffin B, Hautefeuille P, Matuchansky C, et al. Segmental reversal of the small bowel as an alternative to intestinal transplantation in patients with short bowel syndrome. Ann Surg. 1997;225:401–407
     • View In Article
     • MEDLINE
     • CrossRef
176. Trinkle JK, Bryant LR. Reversed colon segment in an infant with massive small bowel resection: a case report. J Ky Med Assoc. 1967;65:1090–1091
     • View In Article
     • MEDLINE
177. Garcia VF, Templeton JM, Eichelberger MR, Koop CE, Vinograd I. Colon interposition for the short bowel syndrome. J Pediatr Surg. 1981;16:994–995
     • View In Article
     • Abstract
     • CrossRef
178. Glick PL, de Lorimier AA, Adzick NS, Harrison MR. Colon interposition: an adjuvant operation for short-gut syndrome. J Pediatr Surg. 1984;19:719–725
     • View In Article
     • Abstract
     • CrossRef
179. Brolin RE. Colon interposition for extreme short bowel syndrome: a case report. Surgery. 1986;100:576–580
     • View In Article
     • MEDLINE
180. Yagi T, Nakagawa K, Sadamori H, Hashimoto M, Kamikawa Y, Tanaka N. Antiperistaltic transverse colostomy for massive bowel necrosis following surgery for an abdominal aortic aneurysm: report of a case. Surg Today. 1997;27:554–558
     • View In Article
     • MEDLINE
     • CrossRef
181. Waddell WR, Kern F, Halgrimson CG, Woodbury JJ. A simple jejunocolic “valve.” For relief of rapid transit and the short bowel syndrome. Arch Surg. 1970;100:438–444
     • View In Article
     • MEDLINE
182. Ricotta J, Zuidema GD, Gadacz TR, Sadri D. Construction of an ileocecal valve and its role in massive resection of the small intestine. Surg Gynecol Obstet. 1981;152:310–314
     • View In Article
     • MEDLINE
183. Georgeson K, Halpin D, Figueroa R, Vincente Y, Hardin W. Sequential intestinal lengthening procedures for refractory short bowel syndrome. J Pediatr Surg. 1994;29:316–320 discussion 320-311
     • View In Article
     • Abstract
     • CrossRef
184. Thompson JS, Langnas AN, Pinch LW, Kaufman S, Quigley EM, Vanderhoof JA. Surgical approach to short-bowel syndrome. Experience in a population of 160 patients. Ann Surg. 1995;222:600–605 discussion 605-607
     • View In Article
     • MEDLINE
     • CrossRef
185. Mackby JM, Richards V, Gilfillan RS, Florida R. Methods of increasing the efficiency of residual small bowel segments. Am J Surg. 1965;109:32–38
     • View In Article
     • MEDLINE
     • CrossRef
186. Camprodon R, Guerrero JA, Salva JA, Jornet J. Shortened small bowel syndrome. Mackby's operation. Am J Surg. 1975;129:585–586
     • View In Article
     • MEDLINE
     • CrossRef
187. Devine RM, Kelly KA. Surgical therapy of the short bowel syndrome. Gastroenterol Clin North Am. 1989;18:603–618
     • View In Article
     • MEDLINE
188. Bianchi A. Intestinal loop lengthening—a technique for increasing small intestinal length. J Pediatr Surg. 1980;15:145–151
     • View In Article
     • Abstract
     • CrossRef
189. Bianchi A. Longitudinal intestinal lengthening and tailoring: results in 20 children. J R Soc Med. 1997;90:429–432
     • View In Article
     • MEDLINE
190. Weber TR. Isoperistaltic bowel lengthening for short bowel syndrome in children. Am J Surg. 1999;178:600–604
     • View In Article
     • Abstract
     • Full Text
     • Full-Text PDF (168 KB)
     • CrossRef
191. Thompson JS, Pinch LW, Young R, Vanderhoof JA. Long-term outcome of intestinal lengthening. Transplant Proc. 2000;32:1242–1243
     • View In Article
     • Full Text
     • Full-Text PDF (50 KB)
     • CrossRef
192. Boeckman CR, Traylor R. Bowel lengthening for short gut syndrome. J Pediatr Surg. 1981;16:996–999
     • View In Article
     • Abstract
     • CrossRef
193. Waag KL, Hosie S, Wessel L. What do children look like after longitudinal intestinal lengthening?. Eur J Pediatr Surg. 1999;9:260–262
     • View In Article
     • MEDLINE
     • CrossRef
194. Sitges-Serra A. Strategies for prevention of catheter-related bloodstream infections. Support Care Cancer. 1999;7:391–395
     • View In Article
     • MEDLINE
     • CrossRef
195. Sigurdsson L, Reyes J, Kocoshis SA, et al.  Bacteremia after intestinal transplantation in children correlates temporally with rejection or gastrointestinal lymphoproliferative disease. Transplantation. 2000;70:302–305
     • View In Article
     • MEDLINE
     • CrossRef
196. 2000 Annual Report. The U.S. Scientific Registry of Transplant Recipients and The Organ Procurement and Transplantation Network. Transplant data 1990-1999. U.S. Department of Health and Human Services, Health Resources and Services Administration, Office of Special Programs, Division of Transplantation, Rockville, MD; United Network of Organ Sharing, Richmond VA.
     • View In Article
197. Harper AM, McBride MA, Ellison MD. The UNOS OPTN waiting list, 1988-1998. Clin Transpl. 1999;71–82
     • View In Article
198. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464–470
     • View In Article
     • MEDLINE
     • CrossRef
199. Beath SV, Needham SJ, Kelly DA, Booth IW, Raafat F, Buick RG, et al. Clinical features and prognosis of children assessed for isolated small bowel or combined small bowel and liver transplantation. J Pediatr Surg. 1997;32:459–461
     • View In Article
     • Abstract
     • Full-Text PDF (287 KB)
     • CrossRef
200. de Ville de Goyer J, Mitchell A, Mayer AD, Beath SV, McKiernan PJ, Kelly DA, et al. En block combined reduced liver and small bowel transplants: from large donors to small children. Transplantation. 2000;69:555–559
     • View In Article
     • MEDLINE
     • CrossRef
201. Grant D. Intestinal Transplantation: 1997 Report of the International Registry. Transplantation. 1999;67:1061–1064
     • View In Article
     • MEDLINE
     • CrossRef
202. Cicalese L, Sileri P, Asolati M, Rastellini C, Abcarian H, Benedetti E. Low infectious complications in segmental living related small bowel transplantation in adults. Clin Transplant. 2000;14:567–571
     • View In Article
     • MEDLINE
203. Horslen SP, Kaufman SS, Sudan DL, Fox IJ, Shaw BW, Langnas AN. Isolated liver transplantation in infants with total parenteral nutrition-associated end-stage liver disease. Transplant Proc. 2000;32:1241
     • View In Article
     • Full Text
     • Full-Text PDF (48 KB)
     • CrossRef
204. Sudan DL, Kaufman SS, Shaw BW, Fox IJ, McCashland TM, Schager DF, et al. Isolated intestinal transplantation for intestinal failure. Am J Gastroenterol. 2000;95:1506–1515
     • View In Article
     • MEDLINE
     • CrossRef
205. Pinna AD, Weppler D, Nery J, Ruiz P, Kato T, Khan F, et al. Intestinal transplantation at the University of Miami: five years of experience. Transplant Proc. 2000;32:1226–1227
     • View In Article
     • Full Text
     • Full-Text PDF (68 KB)
     • CrossRef
206. Abu-Elmagd K, Reyes J, Todo S, Rao A, Lee R, Irishm W, et al. Clinical intestinal transplantation: new perspectives and immunologic considerations. J Am Coll Surg. 1998;186:512–527
     • View In Article
     • Abstract
     • Full Text
     • Full-Text PDF (651 KB)
     • CrossRef
207. Langnas AN, Sudan DL, Kaufman SS, Fox IJ, Horslen S, McCashland T, et al. Intestinal transplantation: a single center experience. Transplant Proc. 2000;32:1228
     • View In Article
     • Full Text
     • Full-Text PDF (46 KB)
     • CrossRef
208. Goulet O, Jan D, Lacaille F, Colomb V, Michel JL, Damotte D, et al. Intestinal transplantation in children: preliminary experience in Paris. JPEN J Parenter Enteral Nutr. 1999;23:S121–S125
     • View In Article
     • MEDLINE
     • CrossRef
209. Smith CE. Quality of life in long-term total parenteral nutrition patients and their family caregivers. JPEN. 1993;17:501–506
     • View In Article
210. Jeppesen PB, Langholz E, Mortenson PB. Quality of life in patients receiving home parenteral nutrition. Gut. 1999;44:844–852
     • View In Article
     • MEDLINE
     • CrossRef
211. Rovera GM, DiMartini A, Schoen RE, Rakela J, Abu-Elmagd K, Graham TO. Quality of life of patients after intestinal transplantation. Transplantation. 1998;66:1141–1145
     • View In Article
     • MEDLINE
     • CrossRef