520994 PENXXX10.1177/0148607114520994Journal of Parenteral and Enteral NutritionJeppesen
`
`research-article2014
`
`Invited Review
`
`Spectrum of Short Bowel Syndrome in Adults: Intestinal
`Insufficiency to Intestinal Failure
`
`Palle B. Jeppesen, MD, PhD1
`
`Journal of Parenteral and Enteral
`Nutrition
`Volume 38 Supplement 1
`May 2014 8S –13S
`© 2014 American Society
`for Parenteral and Enteral Nutrition
`DOI: 10.1177/0148607114520994
`jpen.sagepub.com
`hosted at
`online.sagepub.com
`
`Abstract
`Short bowel syndrome (SBS) refers to the malabsorptive state caused by physical or functional loss of portions of the small intestine,
`most commonly following extensive intestinal resection. Such resections hinder absorption of adequate amounts of macronutrients,
`micronutrients, electrolytes, and water, resulting in malnutrition, diarrhea, and dehydration. Clinical features of SBS vary along a
`continuum, depending on the extent and anatomy of intestine lost and the ability of the patient and the remaining intestine to compensate
`for the loss. The impact of SBS can be extensive, leading to diminished health-related quality of life because of its many physical and
`psychological effects on patients. SBS is associated with decreased survival; risk factors for SBS-related mortality include very short
`remnant small bowel, end-jejunal remnant anatomy, and arterial mesenteric infarction as primary cause. Although parenteral nutrition
`and/or intravenous fluid (PN/IV) is a life-saving measure for many patients with SBS, patients with the most severe malabsorption (ie,
`dependent on PN/IV) are at risk for severe, chronic complications and death. Patients’ treatment needs vary depending on disease severity
`and resection type; thus, each patient should be individually managed. This review discusses the spectrum of disease in patients with
`SBS and presents common complications encountered by these patients to highlight the importance of individualized management and
`treatment. (JPEN J Parenter Enteral Nutr. 2014;38(suppl 1):8S-13S)
`
`Keywords
`gastroenterology; parenteral nutrition; adults; home nutrition support; venous access
`
`Short Bowel Syndrome: Overview
`
`Short bowel syndrome (SBS) refers to the malabsorptive state
`caused by physical or functional loss of significant portions of
`the small intestine. In adults, physical losses usually result
`from extensive intestinal resection for recurrent Crohn’s dis-
`ease, mesenteric vascular events (eg, embolism, thrombus),
`trauma, volvulus, malignancy, and complications from previ-
`ous abdominal surgery.1–5 Functional losses are less common
`and occur in the presence of an intact small intestine that is not
`adequately performing its normal digestive and absorptive
`functions; causes include inflammatory bowel disease, radia-
`tion enteritis, recurrent intestinal pseudo-obstruction, and con-
`genital villus atrophy.1,2 Conditions leading to SBS most
`commonly affect the jejuno-ileal segment, although the colon
`may also be affected.2
`
`Types of Intestinal Resection
`Three types of intestinal resection may lead to SBS.6 In patients
`with jejuno-colic anastomosis, all or most of the ileum is
`removed with at least part of the colon remaining. In contrast,
`patients with an end-jejunostomy retain some jejunum, but the
`ileum and colon are completely removed, and the jejunum
`forms the end of the intestines. The third type of intestinal
`resection is the jejuno-ileal anastomosis, predominantly a
`
`jejunal resection, leaving ≥10 cm of terminal ileum remaining
`and the entire colon intact. The impact of each of these resec-
`tions is discussed in more detail in the review on remnant
`bowel pathophysiology by Tappenden7 in this issue and in a
`recent review by Jeppesen et al.8
`
`Incidence and Prevalence
`
`The true incidence and prevalence of SBS in adults are
`unknown because no reliable patient database exists.1,5,9 Best
`estimates are based on numbers of patients receiving long-term
`
`From the 1Department of Medical Gastroenterology, Rigshospitalet,
`Copenhagen, Denmark.
`
`Financial disclosure: The publication of the supplement in which
`this article appears is supported by an educational grant from NPS
`Pharmaceuticals, Inc (Bedminster, NJ). P.B.J. has served as a site
`investigator, an advisory board member, and a consultant for NPS
`Pharmaceuticals, Inc. No financial compensation was provided to
`P.B.J. for the preparation of this work.
`
`Received for publication October 31, 2013; accepted for publication
`December 11, 2013.
`
`Corresponding Author:
`Palle B. Jeppesen, MD, PhD, Department of Medical Gastroenterology,
`Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
`Email: Bekker@dadlnet.dk
`
`
`
`Downloaded from by guest on March 4, 2015pen.sagepub.com
`
`
`
`Page 1
`
`

`
`Jeppesen
`
`9S
`
`parenteral nutrition and/or intravenous fluid (PN/IV) support
`and do not account for patients who did not receive or who
`were weaned off PN/IV. Approximately 40,000 U.S. adults
`received home-based PN/IV in 1992, according to a U.S.-
`based patient registry; of these, approximately 10,000 had
`diagnoses consistent with SBS.1,10 In Europe, the incidence
`and prevalence of PN/IV dependence have been estimated at
`2–3 per million and 4 per million, respectively.11,12 According
`to more recent results from a Spanish registry, the prevalence
`of PN/IV dependency is 5 per million adults in that country.13
`Based on data indicating that patients with SBS constitute 35%
`of the European PN/IV population,12 the prevalence of SBS
`can be approximated at 1.4 per million.
`However, the prevalence of SBS in Europe varies by region,
`from 0.4 per million in Poland to approximately 30 per million
`in Denmark.12,14 The prevalence of SBS tends to be lower in
`regions lacking major intestinal rehabilitation centers and
`strong home PN/IV programs, likely because of underreport-
`ing and inability to adequately treat these patients. Nonetheless,
`this patient population is growing; a leading intestinal rehabili-
`tation center in Denmark reported a >2-fold increase in the
`number of patients with PN/IV-dependent SBS per decade
`over the past 40 years.15
`
`Patient Demographics
`
`The lack of a comprehensive database of patients with SBS
`also limits efforts to accurately characterize demographic char-
`acteristics; these can only be inferred from published data. In a
`large multicenter survey of 688 adult patients receiving long-
`term PN/IV support for nonmalignant chronic intestinal fail-
`ure, approximately 75% of the patients had SBS.16 In this
`survey, the mean ± SD age was 52.9 ± 15.2 (range, 18.5–88.0)
`years, most patients were women (57%), and the most com-
`mon primary conditions were mesenteric ischemia (27%),
`Crohn’s disease (23%), and radiation enteritis (11%). However,
`patient demographics can vary widely across different geo-
`graphic regions and among treatment centers.
`A recent study limited to patients with SBS (N = 268)
`reported a median age of 52.5 (range, 18–89) years, a majority
`of female patients (52%), and a mean ± SD body mass index of
`20.7 ± 3.9 kg/m2 at baseline.17 The most common primary con-
`ditions were mesenteric infarction (43%), radiation enteritis
`(23%), surgical complications (12%), Crohn’s disease (6%),
`and soft tissue tumor (6%). Most patients (67%) had jejuno-
`colic anastomoses, 18% had end-jejunostomies, and 15% had
`jejunoileocolic anastomoses.17
`
`Individualized Treatment
`
`As these studies suggest, patients with SBS differ in their
`underlying pathology, remnant bowel anatomy, and demo-
`graphic characteristics. Consequently, treatment recommenda-
`tions also vary.18 The guidelines from the Small Bowel and
`
`Nutrition Committee of the British Society of Gastroenterology
`recommend that patients with SBS be individually managed
`because of their heterogeneity.19
`
`Clinical Features and Effect of
`Malabsorption
`
`Absorption Affected by Resection Site
`
`Clinical features of SBS vary, depending on the extent and
`anatomy of intestinal loss and the ability of the remaining
`intestine to functionally compensate.2 In the first 2 years fol-
`lowing extensive resection, the remnant bowel can function-
`ally adapt in response to the loss of the resected portion.18
`Patient outcomes are typically better for jejunal, as opposed to
`ileal, resections because the ileum adapts structurally and func-
`tionally, whereas the jejunum can adapt only functionally.6,9,18
`Nutrient entry into the ileum triggers a feedback mechanism,
`known as the ileal brake, that slows small bowel transit and
`delays gastric emptying, allowing increased nutrient absorp-
`tion; no such compensatory mechanism exists for the jejunum.6
`Outcomes are also better in patients with a preserved colon
`because the colon helps to slow transit of the luminal contents
`and can compensate for decreased jejunal fluid and carbohy-
`drate absorption.6,20
`The ileocecal valve, the sphincter connecting the small and
`large intestine, has been considered an important regulator of
`intestinal transit speed and a physical barrier to anterograde
`flow of chyme from the large to small intestine.18 For example,
`dogs that underwent construction of an artificial valve follow-
`ing resection of the distal intestine and ileocecal junction exhib-
`ited slower intestinal transit time and lower bacterial colony
`counts in the distal ileum than resected dogs who did not receive
`artificial valves.21 However, other animal studies suggest that
`sphincterectomy does not significantly affect intestinal transit
`time.22,23 Unfortunately, evidence from studies conducted in
`adult humans is sparse due to the rarity of limited ileocecal
`resections. In one small study, 8 patients who underwent resec-
`tion of the distal ileum and proximal colon (including the ileo-
`cecal valve) had intestinal transit times that were similar to
`those of healthy volunteers. Furthermore, no instances of
`anterograde reflux from the colon to the small intestine were
`observed.24 Therefore, it is likely that the role and function of
`the ileocecal valve may have been overestimated. However, the
`area in which the valve is located represents an important site
`for hormonal secretion. Feedback hormones, including gluca-
`gon-like peptides 1 and 2 and peptide YY, mediate important
`effects on gastrointestinal secretions, motility, and growth.7
`Patients with SBS are often classified according to the
`length of intestine resected. However, because adult intestinal
`lengths can vary greatly, classifications according to remnant
`bowel length are usually more informative.9 Adult patients
`retaining less than one-third of the jejuno-ileal segment (≤200
`cm) typically experience symptoms of SBS.2 Patients without
`
`
`
`Downloaded from by guest on March 4, 2015pen.sagepub.com
`
`
`
`Page 2
`
`

`
`10S
`
`Journal of Parenteral and Enteral Nutrition 38(Suppl 1)
`
`SBS can also lead to hypotension and early kidney failure
`because of water and sodium deficiencies, especially in patients
`with a resected colon.6 These patients are susceptible to mag-
`nesium deficiency, which can contribute to increased fatigue
`and depression and may also cause muscle weakness and dys-
`seizure.6
`function, cardiac arrhythmia, and possibly
`Importantly, patients with SBS are at increased risk for infec-
`tion and experience impaired wound healing because of mal-
`nutrition.31 For example, vitamins A and C and the trace
`elements zinc, copper, and selenium contribute to wound heal-
`ing through a variety of mechanisms.32–34 Patients with SBS,
`particularly those patients who are dependent on PN/IV sup-
`port, can manifest deficiencies in these specific nutrients or a
`more generalized protein-calorie malnutrition, which may
`result in delayed wound healing.6,32,35
`
`Classification of Patients With Intestinal Failure
`Based on Parenteral Support Requirements
`
`Based on their need for parenteral support, patients with SBS can
`be classified into multiple groups depending on disease severity
`and resection type (Table 1).36 Because the jejunum absorbs more
`nutrients than fluids, patients with end-jejunostomy typically
`require IV fluid supplementation; however, their need for nutri-
`tion support increases with disease severity. In the most severe
`cases, these patients are PN/IV-dependent. In contrast, the colon
`absorbs water preferentially to nutrients, so patients with remnant
`colon-in-continuity (ie, jejuno-colic or jejuno-ileal anastomoses)
`require more energy than fluid. Similar to patients with end-jeju-
`nostomy, patients with colon-in-continuity require fluid and addi-
`tional nutrition support with increasing disease severity and may
`eventually become PN/IV-dependent.
`
`Role of Parenteral Nutrition and/or
`Intravenous Fluid
`
`PN/IV support provides the nutrition, fluid, and electrolytes
`necessary to maintain health and normal body weight.31 In the
`immediate postoperative period, all patients with SBS require
`PN to make up for nutrition losses and minimize osmotic diar-
`rhea by avoiding oral food intake.37,38 IV fluids and electrolytes
`are also required because extensive fluid loss can lead to severe
`dehydration, hypotension, and electrolyte imbalances.18
`Although some patients can gradually decrease dependence
`on PN/IV support and may eventually be weaned, others
`require long-term parenteral support.37,39 Patients absorbing
`less than one-third of their oral intake and those with very short
`intestinal remnants typically require long-term PN/IV.18,40
`Additional improvement after the 2-year adaptation period is
`uncommon and is limited to a further 5%–10% increase in
`absorptive capacity at most. The likelihood of permanent intes-
`tinal failure after 2 years of PN/IV dependence is 95%.18,41 Two
`years after resection, PN/IV dependence is 49%, decreasing
`only slightly at 5 years to 45%.41
`
`Figure 1. Spectrum of short bowel syndrome ranging from
`intestinal insufficiency to intestinal failure. PS, parenteral
`support. Reproduced with permission from Jeppesen PB. Short
`bowel syndrome—characterisation of an orphan condition
`with many phenotypes. Expert Opinion on Orphan Drugs.
`2013;1:515-525.
`
`a functional colon whose remnant small intestinal length is
`<100 cm and patients with a functional colon and <60 cm of
`small intestine remaining will usually be dependent on PN/IV,
`but this varies depending on the patient’s ability to increase
`oral intake and the absorptive capacity of the remnant bowel.1,18
`An alternative classification considers the proportion of
`ingested nutrients and fluids that are absorbed, and may better
`characterize the extent of intestinal insufficiency or failure
`than classifications based solely on remnant intestinal length
`(Figure 1).1 Patients with intestinal insufficiency are able to
`compensate for malabsorption by increasing oral nutrient
`intake or using pharmacotherapies (eg, antimotility agents),
`resulting in sufficient net absorption of fluid and nutrients.5,25,26
`In contrast, patients with intestinal failure are unable to com-
`pensate with diet or drugs and are PN/IV-dependent.1,5,25
`
`Clinical Consequences
`
`The clinical impact of SBS is far-reaching because these
`patients report lower health-related quality of life than the gen-
`eral population.27,28 Extensive resections can lead to malab-
`sorption of macronutrients, micronutrients, electrolytes, and
`water, resulting in malnutrition, diarrhea, and dehydra-
`tion.2,9,18,29,30 The consequent undernutrition leads to weight
`loss, and low-weight patients report symptoms typical of
`undernutrition, including confusion, difficulty concentrating,
`somnolence, and weakness.6,18,31 Many of these patients also
`report feelings of apathy, depression, and irritability, which
`may impair recovery.6 Patients with SBS may exhibit physical
`signs of undernutrition, such as low body temperature, impaired
`growth and sexual development, and premature aging.6,31
`
`
`
`Downloaded from by guest on March 4, 2015pen.sagepub.com
`
`
`
`Page 3
`
`

`
`Jeppesen
`
`11S
`
`Table 1. Suggested Grading of Intestinal Failure According to the Absolute Average Daily Need for Parenteral Support.36
`
`Parenteral Support
`
`Volume, mL/d [mL/kg/d]
`Energy, kJ/d [kJ/kg/d]
`Sodium, mmol/d [mmol/kg/d]
`Potassium, mmol/d [mmol/kg/d]
`Magnesium, mmol/d [mmol/kg/d]
`Calcium, mmol/d [mmol/kg/d]
`
`Grade 1
`(Borderline)
`
`<1000 [<17]
`<1000 [<17]
`<100 [<1.7]
`<25 [<0.4]
`<5 [<0.08]
`<4 [<0.07]
`
`Severity of Intestinal Failure
`
`Grade 2
`(Mild)
`
`Grade 3
`(Moderate)
`
`Grade 4
`(Severe)
`
`1000–2000 [17–34] 2000–3000 [34–51] 3000–4000 [51–68]
`1000–3000 [17–51] 3000–5000 [51–83] 5000–7000 [83–117]
`100–200 [1.7–3.4]
`200–300 [3.4–5.1]
`300–400 [5.1–6.8]
`25–50 [0.4–0.8]
`50–75 [0.8–1.2]
`75–100 [1.2–1.7]
`5–10 [0.08–0.17]
`10–15 [0.17–0.25]
`15–20 [0.25–0.33]
`4–6 [0.07–0.10]
`6–8 [0.10–0.13]
`8–10 [0.13–0.17]
`
`Grade 5
`(Very Severe)
`
`≥4000 [≥68]
`≥7000 [≥117]
`≥400 [≥6.8]
`≥100 [≥1.7]
`≥20 [≥0.33]
`≥10 [≥0.17]
`
`Values given in brackets represent conversions for a 60-kg person.
`Reproduced with permission from Jeppesen PB. Short bowel syndrome—characterisation of an orphan condition with many phenotypes. Expert Opinion
`in Orphan Drugs. 2013;1:515-525.
`
`The ability to receive home PN/IV (HPN) allows patients
`requiring long-term support to resume some aspects of nor-
`malcy.42 Patients on HPN are advised to consume a hyperpha-
`gic diet, defined as a ≥1.5-fold increase in caloric intake over
`resting energy expenditure.43 Selected patients may be able to
`increase calorie consumption to 300% over presurgery levels.39
`Animal studies suggest that hyperphagia stimulates structural
`and functional intestinal adaptation.44 In humans, adaptive
`hyperphagia is associated with decreased risk of dependence on
`PN/IV for patients with SBS as a result of chronic radiation
`enteritis.45 In addition, patients receiving HPN are frequently
`advised to use oral rehydration, ideally with isotonic solutions
`with a high sodium content, to minimize daytime dehydration;
`however, because of the low palatability of isotonic formula-
`tions, these recommendations are hard to implement.38,40
`Vitamin and mineral status should be monitored regularly, and
`supplementation should be customized for each patient.1
`Common supplements include calcium, magnesium, iron, sele-
`, C, D, E, and K.1,39
`nium, zinc, bicarbonate, and vitamins A, B
`12
`Pharmacological management of symptoms associated with
`SBS may include antidiarrheals to avoid excess fluid loss; H
`
`2
`receptor antagonists and proton pump inhibitors to reduce gas-
`tric secretions and stool losses; and antibiotics, prebiotics, and
`probiotics to combat bacterial overgrowth.9,39,46 Two drugs
`have been approved by the U.S. Food and Drug Administration
`for the treatment of adult patients with SBS, somatropin and
`teduglutide. Clinical data supporting the use of these agents are
`extensively reviewed in the accompanying supplement article
`by Jeppesen.47
`
`Complications
`
`Although PN/IV is a life-saving measure for many patients,
`several complications are common (Table 2).1,42,48,49 Many of
`these are related to the PN/IV catheter, PN/IV composition, and
`malabsorption due to the reduced remnant intestinal anatomy.
`The most common of the catheter-related complications is
`catheter-related bloodstream infection and even sepsis, which
`
`is responsible for most of the morbidity and hospital readmis-
`sions in these patients.48–50 In a systematic review, adults
`receiving HPN experienced catheter-related bacteremia once
`every 2–3 years (0.34 episodes per catheter-year).51 In addition
`to implementation of stringent catheter hygiene, the use of
`catheter locks containing ethanol or antibiotics (e.g., tauro-
`lidine) may decrease infectious complications in these
`patients.52,53 The second most common catheter-related com-
`plication is occlusion, which can be caused by a thrombus
`(0.07 episodes per catheter-year), medication-PN precipitate,
`catheter-related mechanical problems, or lipid build-up.20,48,49
`Hepatobiliary disorders, including steatosis, cholestasis, gall-
`stones, and hepatic fibrosis, are also associated with PN/IV
`dependence.54 Evidence from preclinical and clinical studies
`suggests that components of PN could be hepatotoxic due to the
`presence of excess lipids, particularly ω-6 polyunsaturated fatty
`acids, or high levels of phytosterols.54 Uncomplicated liver ste-
`atosis may be caused by an excess of carbohydrates supplied in
`PN solution.55 Several studies of patients receiving long-term
`PN/IV support have found that cholestasis is most likely to occur
`in patients with the shortest remnant bowel or in those with
`moderate-to-high lipid content in the PN emulsion.49 Other fac-
`tors implicated in the pathogenesis of PN-associated liver disease
`include recurrent sepsis, small bowel bacterial overgrowth, cho-
`line or taurine deficiencies, and absence of enteral feeding.54,56
`Mildly abnormal liver function tests are observed in up to
`99% of patients receiving PN, but may also be related to the
`primary pathologic condition.48,57,58 The incidence of severe
`liver dysfunction in these patients is much lower. In a study of
`107 PN-dependent patients, almost half had deranged liver
`function tests, but none progressed to decompensated liver dis-
`ease over a median follow-up of 19 months.58 Salvino et al57
`reported a severe liver dysfunction rate of 4% among 208
`patients on PN support, only 1 of whom had PN-associated
`liver disease. Furthermore, in adults, death caused by intestinal
`failure–associated liver disease is rare when patients are man-
`aged in specialized centers. In a cohort of 509 PN-dependent
`SBS patients treated over the course of 4 decades at the
`
`
`
`Downloaded from by guest on March 4, 2015pen.sagepub.com
`
`
`
`Page 4
`
`

`
`12S
`
`Journal of Parenteral and Enteral Nutrition 38(Suppl 1)
`
`Table 2. Potential Adverse Effects of Parenteral Nutrition.1,42,48,49
`
`Affected System
`
`Catheter Related
`
`Toxicities
`
`Biliary
`
`Hepatic
`
`Renal
`
`Skeletal
`
`• 
`
`• 
`
` Catheter-related bloodstream 
`infections
` Infectious “metastasis” 
`(endocarditis, osteomyelitis,
`etc)
` Catheter-related central 
`venous thrombosis
`•  Loss of venous access
`
`• 
`
`•  Aluminum
`•  Chromium
`•  Manganese
`
`•  Sludge
`•  Gallstones
` Gallbladder 
`• 
`dysmotility
` Acalculous 
`cholecystitis
`
`• 
`
`•  Steatosis
`•  Cholestasis
`•  Fibrosis
`•  Cirrhosis
` End-stage liver 
`• 
`disease
`
`•  Hyperoxaluria
`•  Kidney stones
`• 
` Impairment of 
`tubular function
`
`•  Osteoporosis
`•  Osteopenia
`•  Osteomalacia
`
`Rigshospitalet in Denmark, the mortality rate from intestinal
`failure–associated liver disease was 2.6%.15
`Patients’ altered intestinal anatomy may lead to complica-
`tions. In a normal bowel, various mechanisms, including gas-
`tric acid secretions and intestinal motility, ensure an appropriate
`intestinal bacterial composition; however, SBS-related intesti-
`nal resection impairs intestinal motility, resulting in luminal
`stasis and excessive bacterial proliferation.55
`content
`Consequences of bacterial overgrowth can include fatty acid
`and carbohydrate malabsorption as well as sepsis.20
`
`Survival
`
`SBS is associated with decreased survival. Actuarial survival
`probabilities for adults with nonmalignant SBS at 1, 5, and 10
`years have been reported as 94%, 70%, and 52%, respec-
`tively.17 Slightly lower survival rates were reported for patients
`with SBS secondary to radiation therapy for abdominal and
`pelvic malignancies (83% at 1 year and 68% at 5 years).59
`A number of risk factors for SBS-related mortality have
`been reported. A study of 268 adult patients with nonmalignant
`SBS found 3 independent risk factors: end-jejunostomy, a pri-
`mary condition of arterial mesenteric infarction, and a history
`of cancer. In contrast, age <60 years was associated with sig-
`nificantly increased survival.17 A larger study of patients
`receiving HPN found that the risk of HPN-related death
`increases with duration of HPN support.60 Although 1 or 2 hos-
`pital readmissions are attributed to PN/IV per patient each
`year, PN/IV complications account for only 5%–20% of mor-
`tality in these patients.16,61,62
`
`Conclusions
`
`SBS is a heterogeneous disorder covering a spectrum ranging
`from intestinal insufficiency to intestinal failure. Because of
`the large degree of variability in disease severity and the differ-
`ent types of resection, SBS patients require individualized
`approaches to treatment that, it is hoped, will minimize com-
`plications, improve quality of life, and decrease SBS-associated
`mortality.
`
`Acknowledgments
`Medical writing assistance was provided by Amanda Kelly,
`MPhil, MSHN, of Complete Healthcare Communications, Inc
`(Chadds Ford, PA, USA) under the direction of the author. Dr
`Jeppesen is responsible for the content of this manuscript and had
`final approval of all revisions.
`
`References
` 1. Buchman AL, Scolapio J, Fryer J. AGA technical review on short
`bowel syndrome and
`intestinal
`transplantation. Gastroenterology.
`2003;124:1111-1134.
` 2. Wilmore DW, Byrne TA, Persinger RL. Short bowel syndrome: new ther-
`apeutic approaches. Curr Probl Surg. 1997;34:389-444.
` 3. Buchman AL. The clinical management of short bowel syndrome: steps to
`avoid parenteral nutrition. Nutrition. 1997;13:907-913.
` 4. Vanderhoof JA, Langnas AN. Short-bowel syndrome in children and
`adults. Gastroenterology. 1997;113:1767-1778.
` 5. O’Keefe SJ, Buchman AL, Fishbein TM, Jeejeebhoy KN, Jeppesen PB,
`Shaffer J. Short bowel syndrome and intestinal failure: consensus defini-
`tions and overview. Clin Gastroenterol Hepatol. 2006;4:6-10.
` 6. Nightingale JMD. The short bowel. In: Nightingale JMD, ed. Intestinal
`Failure. London, UK: Greenwich Medical Media; 2001:177-198.
` 7. Tappenden KA. Pathophysiology of short bowel syndrome: consider-
`ations of resected and residual anatomy. JPEN J Parenter Enteral Nutr.
`2014;38(suppl 1):14S-22S.
` 8. Jeppesen PB. The non-surgical treatment of adult patients with short
`bowel syndrome. Expert Opinion in Orphan Drugs. 2013;1:527-538.
` 9. DiBaise JK. Management of the short bowel syndrome. In: DeLegge MH,
`ed. Nutrition and Gastrointestinal Disease. Totowa, NJ: Humana Press;
`2007:177-204.
` 10. North American Home Parenteral Nutrition and Enteral Nutrition Patient
`Registry Annual Report. Albany, NY: Oley Foundation; 1994.
` 11. Mughal M, Irving M. Home parenteral nutrition in the United Kingdom
`and Ireland. Lancet. 1986;2:383-387.
` 12. Van Gossum A, Bakker H, Bozzetti F, et al. Home parenteral nutrition in
`adults: a European multicentre survey in 1997. ESPEN–Home Artificial
`Nutrition Working Group. Clin Nutr. 1999;18:135-140.
` 13. Juana-Roa J, Wanden-Berghe C, Sanz-Valero J. [The reality of home-
`based parenteral nutrition in Spain]. Nutr Hosp. 2011;26:364-368.
` 14. Jeppesen PB. Teduglutide, a novel glucagon-like peptide 2 analog,
`in the treatment of patients with short bowel syndrome. Therap Adv
`Gastroenterol. 2012;5:159-171.
` 15. Brandt CF, Bangsgaard L, Jess T, et al. The evolution of treatment
`of patients with intestinal failure with home parenteral nutrition.
`Gastroenterology. 2012;142:S613-S614.
`
`
`
`Downloaded from by guest on March 4, 2015pen.sagepub.com
`
`
`
`Page 5
`
`

`
`Jeppesen
`
`13S
`
` 16. Pironi L, Hebuterne X, Van Gossum A, et al. Candidates for intestinal
`transplantation: a multicenter survey in Europe. Am J Gastroenterol.
`2006;101:1633-1643; quiz 1679.
` 17. Amiot A, Messing B, Corcos O, Panis Y, Joly F. Determinants of home
`parenteral nutrition dependence and survival of 268 patients with non-
`malignant short bowel syndrome. Clin Nutr. 2013;32:368-374.
` 18. Sundaram A, Koutkia P, Apovian CM. Nutritional management of short
`bowel syndrome in adults. J Clin Gastroenterol. 2002;34:207-220.
` 19. Nightingale J, Woodward JM, Small Bowel Nutrition Committee of
`the British Society of Gastroenterology. Guidelines for management of
`patients with a short bowel. Gut. 2006;55(suppl 4):iv1-12.
` 20. Donohoe CL, Reynolds JV. Short bowel syndrome. Surgeon. 2010;8:270-279.
` 21. 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.
` 22. Johansson H, Nylander G. Ileo-colic transit in rats subjected to ileo-caecal
`resection. Acta Chir Scand. 1969;135:455-458.
` 23. Neri M, Phillips SF, Fich A, Haddad AC. Canine ileocolonic sphincter:
`flow, transit, and motility before and after sphincterotomy. Am J Physiol.
`1991;260:G284-G289.
` 24. Fich A, Steadman CJ, Phillips SF, et al. Ileocolonic transit does not change
`after right hemicolectomy. Gastroenterology. 1992;103:794-799.
` 25. Jeppesen PB, Mortensen PB. Intestinal failure defined by measurements
`of intestinal energy and wet weight absorption. Gut. 2000;46:701-706.
` 26. Messing B, Pigot F, Rongier M, Morin MC, Ndeindoum U, Rambaud JC.
`Intestinal absorption of free oral hyperalimentation in the very short bowel
`syndrome. Gastroenterology. 1991;100:1502-1508.
` 27. Kalaitzakis E, Carlsson E, Josefsson A, Bosaeus I. Quality of life in short-
`bowel syndrome: impact of fatigue and gastrointestinal symptoms. Scand
`J Gastroenterol. 2008;43:1057-1065.
` 28. Carlsson E, Bosaeus I, Nordgren S. Quality of life and concerns in patients
`with short bowel syndrome. Clin Nutr. 2003;22:445-452.
` 29. Misiakos EP, Macheras A, Kapetanakis T, Liakakos T. Short bowel syndrome:
`current medical and surgical trends. J Clin Gastroenterol. 2007;41:5-18.
` 30. Shanbhogue LK, Molenaar JC. Short bowel syndrome: metabolic and sur-
`gical management. Br J Surg. 1994;81:486-499.
` 31. Van Gossum A, Cabre E, Hebuterne X, et al. ESPEN guidelines on paren-
`teral nutrition: gastroenterology. Clin Nutr. 2009;28:415-427.
` 32. Sriram K, Lonchyna VA. Micronutrient supplementation in adult nutri-
`tion therapy: practical considerations. JPEN J Parenter Enteral Nutr.
`2009;33:548-562.
` 33. Mandal A. Do malnutrition and nutritional supplementation have an effect
`on the wound healing process? J Wound Care. 2006;15:254-257.
` 34. Bajpai S, Mishra M, Kumar H, et al. Effect of selenium on connexin
`expression, angiogenesis, and antioxidant status in diabetic wound heal-
`ing. Biol Trace Elem Res. 2011;144:327-338.
` 35. Ayello EA, Thomas DR, Litchford MA. Nutritional aspects of wound
`healing. Home Healthc Nurse. 1999;17:719-729; quiz 730.
` 36. Jeppesen PB. Short bowel syndrome—characterisation of an orphan
`condition with many phenotypes. Expert Opinion in Orphan Drugs.
`2013;1:515-525.
` 37. Matarese LE. Nutrition and fluid optimization for patients with short
`bowel syndrome. JPEN J Parenter Enteral Nutr. 2013;37:161-170.
` 38. Jeejeebhoy KN. Successful management of the short bowel syndrome.
`Trop Gastroenterol. 2010;31:244-248.
` 39. Buchman AL. Short-bowel syndrome. Clin Gastroenterol Hepatol.
`2005;3:1066-1070.
` 40. Nightingale J, Spiller R. Normal intestinal anatomy and physiology.
`In: Nightingale JMD, ed. Intestinal Failure. London, UK: Greenwich
`Medical Media; 2001:15-36.
`
` 41. Messing B, Crenn P, Beau P, Boutron MC, Rambaud JC, Matuchansky C.
`Long-term survival and parenteral nutrition-dependency of adult patients
`with nonmalignant short bowel. Transplant Proc. 1998;30:2548.
` 42. DiBaise JK. Home parenteral nutrition: complications, survival, costs and
`quality of life. In: Langnas A, Goulet O, Quigley EM, Tappenden KA, eds.
`Intestinal Failure: Diagnosis, Management and Transplantation. Oxford,
`UK: Blackwell Publishing; 2008.
` 43. Crenn P, Morin MC, Joly F, Penven S, Thuillier F, Messing B. Net diges-
`tive absorption and adaptive hyperphagia in adult short bowel patients.
`Gut. 2004;53:1279-1286.
` 44. Menge H, Grafe M, Lorenz-Meyer H, Riecken EO. The influence of food
`intake on the development of structural and functional adaptation follow-
`ing ileal resection in the rat. Gut. 1975;16:468-472.
` 45. Amiot A, Joly F, Lefevre JH, et al. Long-term outcome after exten-
`sive intestinal resection for chronic radiation enteritis. Dig Liver Dis.
`2013;45:110-114.
` 46. Kumpf VJ. Pharmacologic management of diarrhea in patients with short
`bowel syndrome. JPEN J Parenter Enteral Nutr. 2014;38(suppl 1):38S-44S.
` 47. Jeppesen PB. Pharmacologic options for intestinal rehabilitation in
`patients with short bowel syndrome. JPEN J Parenter Enteral Nutr.
`2014;38(suppl 1):45S-52S.
` 48. Howard L, Ashley C. Management of complications in patients receiving
`home parenteral nutrition. Gastroenterology. 2003;124:1651-1661.
` 49. Buchman AL. Complications of long-term home total parenteral nutrition:
`their identification, prevention and treatment. Dig Dis Sci. 2001;46:1-18.
` 50. Winkler MF, Smith CE. Clinical, social, and economic impacts of
`home parenteral nutrition dependence in short bowel syndrome. JPEN J
`Parenter Enteral Nutr. 2014;38(suppl 1):32S-37S.
` 51. Richards D