Current Opinion in Gastroenterology:
SMALL INTESTINE: Edited by Fergus Shanahan
Short bowel syndrome and small bowel transplantation
DiBaise, John K.
Division of Gastroenterology, Mayo Clinic, Scottsdale, Arizona, USA
Correspondence to John K. DiBaise, MD, Professor of Medicine, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA. Tel: +1 480 301 6990; fax: +1 480 301 6737; e-mail: email@example.com
Purpose of review: The purpose of this review is to provide an update of recent advances in the areas of short bowel syndrome (SBS) and small bowel transplantation (SBT).
Recent findings: Recent reports from two of the largest multicenter randomized, controlled trials in patients with SBS support the safety and efficacy of teduglutide as an aid to parenteral nutrition weaning. In well selected SBS patients, outcomes as diverse as survival, macronutrient absorption and parenteral nutrition weaning are improved after autologous gastrointestinal reconstructive surgery. SBT is no longer considered investigational and given improved outcomes noted in recent reports, indications for transplantation are expanding. Although SBT early survival rates are approaching those of other organ allografts, long-term graft survival remains suboptimal.
Summary: Recently available trophic factors hold promise as aids in restoring freedom from parenteral nutrition support; however, their long-term benefits, preferred timing of administration in relation to the onset of SBS, optimal patient selection for use, duration of treatment and cost effectiveness require further study. Despite recent evidence of improved early survival after SBT, more dedicated research is needed to design more effective strategies to better tolerize small bowel grafts, prevent rejection and, ultimately, improve long-term outcomes. Reserved for well selected patients, autologous gastrointestinal reconstruction should be considered complementary and not antagonistic to SBT.
The purpose of this review is to provide an update of recent advances in the areas of short bowel syndrome (SBS) and small bowel transplantation (SBT). Although there have been many advances in both areas in the last few years, in this review, we will focus on the recent developments pertaining to the use of trophic factors and autologous gastrointestinal reconstruction (AGIR) to wean parenteral nutrition and avoid SBT. We will also provide an update on the issues related to expanding indications and improving outcomes for SBT.
SHORT BOWEL SYNDROME
SBS is a highly disabling malabsorptive condition resulting most commonly from extensive intestinal resection and characterized by the inability to maintain protein-energy, fluid, electrolyte or micronutrient balances when on a regular diet . SBS is associated with significant morbidity and mortality, a reduced quality of life and high healthcare costs . Chronic diarrhea, steatorrhea, fluid-electrolyte imbalances and macronutrient and micronutrient deficiencies, often requiring enteral and/or parenteral nutrition support at home, frequently complicate its course [3▪]. Following massive intestinal resection, a process of intestinal adaptation occurs in which the remaining bowel undergoes macroscopic and microscopic morphologic and functional changes in response to a variety of internal and external stimuli including nutrients, gastrointestinal secretions, hormones, growth factors and other genetic/biochemical factors in order to increase its absorptive ability . Intestinal adaptation is highly variable, unique to each individual and usually occurs during the first 2 years following massive intestinal resection in adults; longer and perhaps more vigorously in children.
Pharmacologically enhancing intestinal adaptation
Approximately, 70% of those with newly acquired SBS are eventually able to be discharged from the hospital, usually on parenteral nutrition . As the bowel adapts allowing greater nutrient and fluid absorption, parenteral nutrition requirements decrease. In nonmalignant SBS, parenteral nutrition dependency at 1, 2 and 5 years was recently reported to be 74, 64 and 48%, respectively . In SBS, the goal of treatment is to enhance this adaptation process in order to minimize parenteral nutrition complications, improve quality of life and, ultimately, restore enteral autonomy . The current understanding of the adaptation process has led to the study of hormones, nutrients and growth factors in experimental models of SBS and in humans with SBS who have been unable to achieve enteral independence during the adaptive period. In 2005, the U.S. Food and Drug Administration (FDA) approved the use of recombinant-human growth hormone (r-hGH) (Zorbtive; Serono Inc., Rockland, Massachusetts, USA) for patients with SBS as an aid for parenteral nutrition weaning. In 2012, a glucagon-like peptide-2 (GLP-2) analogue, teduglutide, was also approved by the FDA (Gattex; NPS Pharmaceuticals, Bedminster, New Jersey, USA) as an aid for parenteral nutrition weaning and is also available in Europe (Revestive; Nycomed, Zurich, Switzerland).
In 1995, Byrne et al. reported on 47 patients treated with a combination of growth hormone, oral glutamine and an optimized SBS diet for 3 weeks followed by continued use of the diet and glutamine. With follow-up for as long as 5 years, they showed that 40% of patients could be weaned completely from parenteral nutrition, whereas another 40% could make significant reductions in their parenteral nutrition use  ushering in the concept of intestinal rehabilitation. More recently, a prospective, randomized, controlled study of r-hGH (0.10 mg/kg/day) and an optimized diet with or without glutamine in 41 parenteral nutrition-dependent SBS patients found a significant reduction in parenteral nutrition requirements (the primary endpoint) in all groups studied at the end of the 4-week treatment period . The extent of reduction, however, was greatest in the group receiving r-hGH in addition to glutamine, and the parenteral nutrition reduction remained significantly reduced 12 weeks later only in the r-hGH with glutamine group. Despite the reports of the success, conflicting findings seen in three short-term, randomized, controlled nutrient balance studies with respect to nutrient and wet weight absorption [11–13] using this combination of r-hGH and glutamine, have led to a considerable amount of skepticism surrounding the long-term benefits of this approach, and its use has not been widely adopted into clinical practice . Furthermore, side-effects of r-hGH including peripheral edema, arthralgias and carpal tunnel syndrome are relatively common, and there is also concern about a potential increased risk of colorectal cancer in patients receiving growth hormone if required to be administered over a longer period of time.
GLP-2, secreted from distal small intestine and proximal colon mucosal L-cells, plays a role in intestinal adaptation and has fewer systemic effects than growth hormone. Teduglutide, a recombinant, degradation-resistant, longer acting GLP-2 analogue, was shown to be safe, well tolerated, intestinotrophic and significantly increase intestinal wet weight but not energy absorption in 16 SBS patients . Teduglutide was recently studied in two large multinational, randomized, double-blind, placebo-controlled trials. In the first study, 83 SBS patients were separated into three treatment arms (placebo, 0.05 and 0.10 mg/kg/day) and treated for 6 months following a parenteral nutrition optimization period. Parenteral nutrition weaning was the primary endpoint (20% reduction at weeks 20 and 24). Teduglutide was found to be safe and well tolerated; however, only the lower teduglutide dose significantly reduced parenteral nutrition requirements, and only three patients were completely weaned from parenteral nutrition . Villus height, plasma citrulline concentration and lean body mass were significantly increased in the teduglutide groups compared with placebo; no evidence of dysplasia in the intestinal samples was detected . The second trial compared the lower dose of teduglutide to placebo administered for 6 months in 86 adult SBS patients and utilized a more aggressive parenteral nutrition weaning strategy (10–30% reductions at 2-weekly intervals) [18▪▪]. Once again, a significant benefit of teduglutide over placebo was seen; responders were more than twice the percentage in those receiving teduglutide (63 vs. 30%, P = 0.02). The mean weekly reduction in parenteral nutrition volume was 4.4 l in the teduglutide group compared with 2.3 l in the placebo group. Fifty-four percent of those receiving teduglutide reduced at least one parenteral nutrition infusion day/week compared with 23% for placebo. Gastrointestinal side-effects including abdominal pain, nausea, stomal changes, abdominal distension and peripheral edema were reported most frequently; resolution occurred with treatment continuation or temporary discontinuation in most instances.
Recently, longer-term data have become available after completion of a 28-week open-label extension of the original trial and suggest a sufficient safety profile and continued improvements in parenteral nutrition weaning . The most common adverse events were headache, nausea and abdominal pain. At week 52, 68% of the 0.05 mg/kg/day dose group and 52% of the 0.10 mg/kg/day group had an at least 20% reduction in parenteral nutrition, with a reduction of 1 or more days of parenteral nutrition/week in 68 and 37%, respectively.
Autologous gastrointestinal reconstruction
In spite of the tremendous improvements in early survival after SBT, Abu-Elmagd et al. recently reported an overall small bowel graft survival of 59 and 50% at 10 and 15 years, respectively. Chronic rejection and complications of long-term immunosuppression remain threats to allograft longevity. For these reasons, AGIR procedures have gained a new place in the multidisciplinary management of SBS. AGIR refers to surgical procedures devised with the goal of maximizing the function of the SBS patient's existing intestine and should be considered complementary to SBT [21▪]. Currently, two approaches are most commonly employed: the reversed intestinal segment to slow intestinal transit and intestinal lengthening procedures to enhance mucosal absorptive surface and improve stasis. The choice of surgery is influenced by the existing bowel length, function and caliber and the condition of the patient.
A recent case–control study of 17 adult SBS patients who had undergone the reversed intestinal segment procedure found that the surgery resulted in a gain in macronutrient absorption and was associated with a lower parenteral nutrition dependence . The same group also recently reported that in 38 adult SBS patients with a reversed jejunal segment of 10–12 cm, 45% of patients had been weaned from parenteral nutrition after 5 years of follow-up, whereas the remainder had reduced their parenteral nutrition requirements from 7 to 4 days/week . Because obstructive symptoms, intestinal ischemia and anastomotic leak/stricture remain potential problems and because of limited long-term data available with this procedure, it should only be considered in individuals with rapid transit and nondilated, relatively long small bowel length.
Intestinal lengthening is generally considered the gold standard approach to AGIR in SBS with intestinal failure. A prerequisite for intestinal lengthening is dilatation of the remnant bowel. Longitudinal intestinal lengthening and tailoring (LILT aka Bianchi procedure) was first introduced in 1980; however, its use has been limited by its technical complexity, risk of anastomotic leak/stricture and risk of injury to the mesenteric vasculature . An alternative and currently more popular lengthening technique called serial transverse enteroplasty (STEP) was first described in 2003 . STEP involves serial transverse applications of a linear stapler from alternating directions in an overlapping and partially transecting fashion creating an accordion-like configuration to the bowel. This procedure is less technically challenging than the Bianchi procedure, is more applicable for short segments and when the bowel diameter is asymmetrical along its length, may be repeated, and may be performed in those SBS patients who have already undergone a Bianchi procedure. A recent retrospective, single-center report provides evidence of long-term clinical benefits including enteral tolerance and catch-up growth after STEP in a pediatric population . Although a proper comparison of these two techniques is difficult, a recent systematic review compared outcomes in children with SBS who had undergone either the LILT or STEP procedures . Significant parenteral nutrition weaning was noted after both procedures; however, the LILT procedure seems to be associated with a higher rate of eventual SBT.
SMALL BOWEL TRANSPLANTATION
SBT is attractive as a treatment option for patients with SBS and associated intestinal failure as it replaces the missing or diseased intestine and offers the potential for return to normal activities and intestinal function . SBT includes a group of options linked together by a shared vascular supply. The most common classification, recently revised , includes the following options: transplant of the small bowel alone; transplant of the liver together with the small bowel; and transplant of the entire gastrointestinal tract en bloc with the liver and pancreas. A modification of the last option includes the stomach-duodenum-pancreas and intestine without the liver. Because of the need for long-term immunosuppression and its attendant risks, SBT is reserved for SBS patients with a life-long need for parenteral nutrition when complications of parenteral nutrition occur .
The indications for SBT have been described in published guidelines established by a consensus conference of the Intestinal Transplant Association and include permanent intestinal failure with at least one of the following complications: end-stage intestinal failure-associated liver disease, loss of two major venous access sites for administration of parenteral nutrition and severe life-threatening and/or recurrent catheter-associated blood stream infections . Recently, Pironi et al. in a large multicenter European registry confirmed that these indications, which were initially described for pediatric patients, were also appropriate in adults. This large cohort study examined adults on parenteral nutrition for an average of 6 years prior to enrollment and found that in patients with indications for transplantation due to home parenteral nutrition failure, survival was better after isolated SBT than in those patients remaining on parenteral nutrition (89 vs. 80%, respectively after 3 years of follow-up).
More recently, Vianna et al.[32▪] suggested expansion of indications for SBT to include patients with slow-growing or unresectable tumors of the mesenteric root and patients with extensive mesenteric venous thrombosis who otherwise would require liver transplantation but could not safely undergo isolated liver transplant due to lack of portal venous inflow for the liver allograft. Other conditions suggested as expanded indications by this group include the frozen abdomen due to severe adhesions and extensive enterocutaneous fistula formation . At present, given an absence of comparative outcomes in these populations with and without transplantation, decisions regarding these expanded indications should be individualized as to the likelihood of successful outcome. Although not standard of care to offer SBT electively in patients who do not have life-threatening complications of parenteral nutrition, elective intestinal transplantation is increasingly being considered.
With the introduction of more potent immunosuppressive medications and improvements in surgical techniques and postoperative care, early outcomes following SBT have steadily improved. Indeed, SBT patient early survival rates are approaching those of other organ allografts, particularly in those patients who are well enough to wait at home until the time of their transplant .
The Scientific Registry of Transplant Recipients (SRTR) publishes center-specific reports of the patient and graft survival for all candidates undergoing SBT in the United States. This audited database is notable for universal capture of patients and independent review of data elements to maximize accuracy. Unfortunately, a major flaw in the reporting of outcomes in the SRTR annual report is the combination of patient and graft survival outcomes of the intestine only grafts to those intestine allografts that include the liver. In addition, 60% of the centers included in the most recent report performed between one and 10 transplants, a volume associated with worse outcomes compared with higher volume centers . The most recent report of the SRTR posted describes 29 programs that have wait-listed pediatric or adult candidates for intestine transplantation [35▪▪]. In this report, 1-year patient survival for transplants performed between 1 January 2009 and 30 June 2011 ranged between 35 and 100% in the 14 programs reporting at least one pediatric SBT and between 50 and 100% in the 13 programs reporting at least one adult SBT. Additionally, this report shows that 1-year graft survival has increased from 59.5% for transplants in 1991–1995 to 72.2% for transplants in 2008–2009. Long-term graft survival rates remain relatively low, however, with 5-year graft survival of 31.6% for transplants in 1991–1995 compared with 50.6% for transplants in 2004–2005.
In contrast to the SRTR reports, the international Intestinal Transplant Registry (ITR) has collected outcomes for virtually all SBT performed at any center around the world since the introduction of SBT. The principal drawback of the ITR is that the source of the data is center self-reported and does not undergo an independent audit. In the most recent publication of the ITR from 2005, 61 programs reported results for nearly 1000 patients who had undergone intestinal transplant procedures, including 433 isolated intestinal transplants, 386 liver-intestine allografts and 170 other transplant procedures that included the small intestine as part of the allograft . The isolated intestine allograft is associated with the best patient survival at least at the earliest time points. The ITR has demonstrated improved graft and patient survival with increasing center experience over time, in those individuals well enough to be called in from home at the time of their transplant, and depending upon the type of induction immunosuppression used.
Decreasing allograft rejection
Complications are more common and often more severe in the early period after SBT than they are after transplantation of other solid organs. The intestine is host to a tremendous number of microorganisms, and its mucosa is populated by immense lymphoid tissue, challenging factors that contribute to the frequency and severity of both early and late complications after SBT including allograft rejection. It has been postulated that ischemia-reperfusion injury, as a consequence of the interruption of blood flow to the transplanted allograft, contributes to rejection via cross-talk of innate and adaptive immune systems stimulated by interplay between the luminal microbes and an impaired epithelial barrier provoking an inflammatory response that exacerbates tissue injury . Recent studies using next-generation sequencing suggest that differences in the ileal microbial ecology occur in SBT graft rejection  playing a role in creating a more hostile luminal microenvironment and raising the possibility of microbiota profiling as a diagnostic biomarker of rejection . Clearly, further studies are needed to clarify the causal nature of this relationship.
Acute rejection occurred in greater than 85% of recipients in the early years with SBT; however, in more recent years, the incidence of acute intestinal allograft rejection has decreased to less than 30% in some high-volume transplant centers [39,40]. This largely relates to improved immunosuppression regimens and the introduction of induction therapy. A virtual cross-matching strategy in which donor-specific antibodies were evaluated to optimize organ allocation and reduce immunologic risk recently demonstrated successful short-term outcomes in sensitized recipients and may represent another approach to reduce rejection and improve outcome [41▪]. Despite the overall decreased incidence of acute allograft rejection, severe rejection is still associated with a high risk of mortality because of the high risk of infection with complete mucosal sloughing and the use of high doses of immunosuppressive agents. Chronic allograft rejection also remains a major barrier to the long-term success of SBT. Recently, the presence of donor-specific antibodies was shown to be associated with worse graft survival suggesting that innovative antidonor-specific antibody strategies, as described above, for example, may be helpful to improve the long-term survival .
The long-term benefits of both r-hGH and teduglutide with respect to parenteral nutrition weaning, parenteral nutrition complications and quality of life require further study as do the preferred timing of administration in relation to the onset of SBS, optimal patient selection for use, duration of treatment and cost effectiveness of both strategies. Similarly, while there are accumulating reports from single center case series regarding the utility of AGIR, evidence of long-term success is limited, the number of centers that perform these procedures is relatively few, and only a small proportion of SBS patients are candidates for these procedures. SBT is no longer considered investigational and given improved outcomes, indications for this treatment are expanding. Decisions regarding these expanded indications should be individualized. Although SBT patient early survival rates are approaching those of other organ allografts, long-term graft survival remains suboptimal. Indeed, chronic allograft rejection remains a major barrier to the long-term success of SBT highlighting the need for further research.
Conflicts of interest
No funding was received for this work, and there are no conflicts of interest to disclose.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
▪ of special interest
▪▪ of outstanding interest
1. O’Keefe SJ, Buchman AL, Fishbein TM, et al. Short bowel syndrome and intestinal failure: consensus definitions and overview. Clin Gastroenterol Hepatol 2006; 4:6–10.
2. AGA technical review on short bowel syndrome and intestinal transplantation. Gastroenterology 2003; 124:1111–1134.
3▪. Thompson JS, Rochling FA, Weseman RA, et al. Current management of short bowel syndrome. Curr Probl Surg 2012; 49:52–115.
A comprehensive review of SBS and its management including AGIR and SBT.
4. Buccigrossi V, Armellino C, Tozzi A, et al. Time and segment-related changes of postresected intestine: a 4-dimensional model of intestinal adaptation. J Pediatr Gastroenterol Nutr 2013; 56:40–45.
5. Thompson JS, Langnas AN, Pinch LW, et al. Surgical approach to short-bowel syndrome. Experience in a population of 160 patients. Ann Surg 1995; 222:600–605.
6. Amiot A, Messing B, Corcos O, et al. Determinants of home parenteral nutrition dependency and survival of 268 patients with nonmalignant short bowel syndrome. Clin Nutr 2013; 32:368–374.
7. DiBaise JK, Young RM, Vanderhoof JA. Intestinal rehabilitation and the short bowel syndrome. Part 2. Am J Gastroenterol 2004; 99:1823–1832.
8. Byrne TA, Persinger RL, Young LS, et al. A new treatment for patients with short-bowel syndrome: growth hormone, glutamine, and a modified diet. Ann Surg 1995; 222:243–254.
9. Byrne TA, Cox S, Karimbakas M, et al. Bowel rehabilitation: an alternative to long-term parenteral nutrition and intestinal transplantation for some patients with short bowel syndrome. Transplant Proc 2002; 34:887–890.
10. Byrne TA, Wilmore DW, Iyer K, et al. Growth hormone, glutamine and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome. A prospective, randomized, placebo-controlled, double-blind clinical trial. Ann Surg 2005; 242:655–661.
11. Scolapio JS, Camilleri M, Fleming CR, et al. Effect of growth hormone, glutamine, and diet on adaptation in short bowel syndrome: a randomized, controlled study. Gastroenterology 1997; 113:1074–1081.
12. 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.
13. Seguy D, Vahedi K, Kapel N, et al. Low-dose growth hormone in adult home parenteral nutrition-dependent short bowel syndrome patients: a positive study. Gastroenterology 2003; 124:293–302.
14. Wales PW, Nasr A, de Silva N, et al. Human growth hormone and glutamine for patients with short bowel syndrome. Cochrane Database Syst Rev 2010; CD006321.
15. Jeppesen PB, Sanguinetti EL, Buchman A, et al. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide analogue, improves intestinal function in short bowel syndrome patients. Gut 2005; 54:1224–1231.
16. Jeppesen PB, Gilroy R, Pertkiewicz M, et al. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut 2011; 60:902–914.
17. Tappenden KA, Edelman J, Joelsson B. Teduglutide enhances structural adaptation of the small intestinal mucosa in patients with short bowel syndrome. J Clin Gastroenterol 2013; 47:602–607.
18▪▪. Jeppesen PB, Pertkiewicz M, Messing B, et al. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology 2012; 143:1473–1481.
An important randomized, controlled study showing the benefits of teduglutide with respect to weaning parenteral nutrition requirements in SBS.
19. O’Keefe SJ, Jeppesen PB, Gilroy R, et al. Safety and efficacy of teduglutide after 52 weeks of treatment in patients with short bowel intestinal failure. Clin Gastroenterol Hepatol 2013; 11:815–823.
20. Abu-Elmagd KM, Kosmach-Park B, Costa G, et al. Long-term survival, nutritional autonomy, and quality of life after intestinal and multivisceral transplantation. Ann Surg 2012; 256:494–508.
21▪. Rege AS, Sudan DL. Autologous gastrointestinal reconstruction: review of the optimal nontransplant surgical options for adults and children with short bowel syndrome. Nutr Clin Pract 2013; 28:65–74.
A recent overview of the autologous gastrointestinal reconstructive procedures including their utility, complications and patient selection.
22. Layec S, Beyer L, Corcos O, et al. Increased intestinal absorption by segmental reversal of the small bowel in adult patients with short-bowel syndrome: a case-control study. Am J Clin Nutr 2013; 97:100–108.
23. Beyer-Berjot L, Joly F, Maggiori L, et al. Segmental reversal of the small bowel can end permanent parenteral nutrition dependency: an experience of 38 adults with short bowel syndrome. Ann Surg 2012; 256:739–745.
24. Bianchi A. Longitudinal intestinal lengthening and tailoring: results in 20 children. J R Soc Med 1997; 90:429–432.
25. Kim HB, Fauza D, Garza J, et al. Serial transverse enteroplasty (STEP): a novel bowel lengthening procedure. J Pediatr Surg 2003; 38:425–429.
26. Ching YA, Fitzgibbons S, Valim C, et al. Long-term nutritional and clinical outcomes after serial transverse enteroplasty at a single institution. J Pediatr Surg 2009; 44:939–943.
27. King B, Carlson G, Khalil BA, et al. Intestinal bowel lengthening in children with short bowel syndrome: systematic review of the Bianchi and STEP procedures. World J Surg 2013; 37:694–704.
28. Fishbein TM. Intestinal transplantation. N Engl J Med 2009; 361:998–1008.
29. Abu-Elmagd KM. The small bowel contained allograft: existing and proposed nomenclature. Am J Transplant 2011; 11:184–185.
30. Kaufman S, Atkinson J, Bianchi A, et al. Indications for pediatric intestinal transplantation: a position paper of the American Society of Transplantation. Pediatr Transplant 2001; 5:80–87.
31. Pironi L, Forbes A, Joly F, et al. Survival of patients identified as candidates for intestinal transplantation: a 3- year prospective follow-up. Gastroenterology 2008; 135:61–71.
32▪. Vianna RM, Mangus RS, Kubal C, et al. Multivisceral transplantation for diffuse portomesenteric thrombosis. Ann Surg 2012; 255:1144–1150.
An important yet controversial report that highlights the potential of expanding the indications for SBT.
33. Mangus RS, Tector AJ, Kubal CA, et al. Multivisceral transplantation: expanding indications and improving outcomes. J Gastrointest Surg 2013; 17:179–186.
34. Grant D, Abu-Elmagd K, Reyes J, et al. on behalf of the Intestine Transplant Registry2003 report of the intestine transplant registry: a new era has dawned. Ann Surg 2005; 241:607–613.
35▪▪. Organ Procurement Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2010 Annual Data Report. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation. Am J Transplant 2012; 12 (Suppl 1):1–156.
Recent report detailing the outcomes of all SBT performed in the United States.
36. Chong A, Alegre M-L. The impact of infection and tissue damage in solid-organ transplantation. Nat Rev Immunol 2012; 12:459–471.
37. Hartman AL, Lough DM, Barupal DK, et al. Human gut microbiome adopts an alternative state following small bowel transplantation. Proc Natl Acad Sci U S A 2009; 106:17187–17192.
38. Oh PL, Martinez I, Sun Y, et al. Characterization of the ileal microbiota in rejecting and nonrejecting recipients of small bowel transplants. Am J Transplant 2012; 12:753–762.
39. Fishbein TM, Kaufman SS, Florman SS, et al. Isolated intestinal transplantation: proof of clinical efficacy. Transplantation 2003; 76:636–640.
40. Sudan DL, Chinnakotla S, Horslen S, et al. Basiliximab decreases the incidence of acute rejection after intestinal transplantation. Transplant Proc 2002; 34:940–941.
41▪. Hawksworth JS, Rosen-Bronson S, Island E, et al. Successful isolated intestinal transplantation in sensitized recipients with the use of virtual crossmatching. Am J Transplant 2012; 12 (Suppl):S33–S42.
An interesting report showing how virtual cross-matching can facilitate transplantation in sensitized patients.
42. Abu-Elmagd KM, Wu G, Costa G, et al. Preformed and de novo donor specific antibodies in visceral transplantation: long-term outcome with special reference to the liver. Am J Transplant 2012; 12:3047–3060.
autologous gastrointestinal reconstruction; intestinal adaptation; short bowel syndrome; small bowel transplantation; trophic factor
© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Highlight selected keywords in the article text.