Skip to main content
SpringerLink
Log in

Intestinal Transplantation

  • Chapter
  • First Online:
Pathology of Transplantation

  • 1236 Accesses

Abstract

Intestinal transplantation has become a viable treatment option for patients with intestinal failure and provides acceptable quality of life for recipients of small bowel allografts. This chapter discusses the pathology of preservation injury, acute cellular and humoral rejection, chronic rejection, mimics of rejection, posttransplant lymphoproliferative disorder in the intestinal allograft and future directions in intestinal transplantation. The current grading scheme for acute rejection as developed at the VIIIth International Small Bowel Transplant Symposium is described in detail and illustrated with figures. The emphasis of the chapter is on the differential diagnostic considerations of a pathologist assessing endoscopic biopsies or resected allografts.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Alican F, Hardy JD, Cayirli M, Varner JE, Moynihan PC, Turner MD, et al. Intestinal transplantation: laboratory experience and report of a clinical case. Am J Surg. 1971;121(2):150–9.

    Article  CAS  PubMed  Google Scholar 

  2. Lillehei RC, Idezuki Y, Feemster JA, Dietzman RH, Kelly WD, Merkel FK, et al. Transplantation of stomach, intestine, and pancreas: experimental and clinical observations. Surgery. 1967;62(4):721–41.

    CAS  PubMed  Google Scholar 

  3. Olivier C, Rettori R, Baur O, Roux J. Orthotopic homotransplantation of the small intestine and of the right and transverse colon in man. J Chir. 1969;98(4):323–30.

    CAS  Google Scholar 

  4. Kirkman RL. Small bowel transplantation. Transplantation. 1984;37(5):429–33.

    Article  CAS  PubMed  Google Scholar 

  5. Grant D, Abu-Elmagd K, Reyes J, Tzakis A, Langnas A, Fishbein T, et al. 2003 report of the intestine transplant registry: a new era has dawned. Ann Surg. 2005;241(4):607–13.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Abu-Elmagd KM, Kosmach-Park B, Costa G, Zenati M, Martin L, Koritsky DA, et al. Long-term survival, nutritional autonomy, and quality of life after intestinal and multivisceral transplantation. Ann Surg. 2012;256(3):494–508.

    Article  PubMed  Google Scholar 

  7. Tzakis AG, Kato T, Levi DM, Defaria W, Selvaggi G, Weppler D, et al. 100 multivisceral transplants at a single center. Ann Surg. 2005;242(4):480–90. discussion 91–3.

    PubMed  PubMed Central  Google Scholar 

  8. Selvaggi G, Gaynor JJ, Moon J, Kato T, Thompson J, Nishida S, et al. Analysis of acute cellular rejection episodes in recipients of primary intestinal transplantation: a single center, 11-year experience. Am J Transplant. 2007;7(5):1249–57.

    Article  CAS  PubMed  Google Scholar 

  9. Kaufman SS, Atkinson JB, Bianchi A, Goulet OJ, Grant D, Langnas AN, et al. Indications for pediatric intestinal transplantation: a position paper of the American Society of Transplantation. Pediatr Transplant. 2001;5(2):80–7.

    Article  CAS  PubMed  Google Scholar 

  10. Pironi L, Joly F, Forbes A, Colomb V, Lyszkowska M, Baxter J, et al. Long-term follow-up of patients on home parenteral nutrition in Europe: implications for intestinal transplantation. Gut. 2011;60(1):17–25.

    Article  PubMed  Google Scholar 

  11. Fishbein TM. Intestinal transplantation. N Engl J Med. 2009;361(10):998–1008.

    Article  CAS  PubMed  Google Scholar 

  12. Smith JM, Skeans MA, Horslen SP, Edwards EB, Harper AM, Snyderf JJ, et al. OPTN/SRTR 2012 annual data report: intestine. Am J Transplant. 2014;14 Suppl 1:97–111.

    Article  PubMed  Google Scholar 

  13. Abu-Elmagd KM, Costa G, Bond GJ, Soltys K, Sindhi R, Wu T, et al. Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg. 2009;250(4):567–81.

    PubMed  Google Scholar 

  14. Lee RG, Tsamandas AC, Abu-Elmagd K, Furukawa H, Hutson WR, Reyes J, et al. Histologic spectrum of acute cellular rejection in human intestinal allografts. Transplant Proc. 1996;28(5):2767.

    CAS  PubMed  Google Scholar 

  15. Martin BA, Kerner JA, Hazard FK, Longacre TA. Evaluation of intestinal biopsies for pediatric enteropathy: a proposed immunohistochemical panel approach. Am J Surg Pathol. 2014;38(10):1387–95.

    Article  PubMed  Google Scholar 

  16. Noguchi Si S, Reyes J, Mazariegos GV, Parizhskaya M, Jaffe R. Pediatric intestinal transplantation: the resected allograft. Pediatr Dev Pathol. 2002;5(1):3–21.

    Article  PubMed  Google Scholar 

  17. Swanson BJ, Talmon GA, Wisecarver JW, Grant WJ, Radio SJ. Histologic analysis of chronic rejection in small bowel transplantation: mucosal and vascular alterations. Transplantation. 2013;95(2):378–82.

    Article  PubMed  Google Scholar 

  18. Nadasdy GM, Bott C, Cowden D, Pelletier R, Ferguson R, Nadasdy T. Comparative study for the detection of peritubular capillary C4d deposition in human renal allografts using different methodologies. Hum Pathol. 2005;36(11):1178–85.

    Article  CAS  PubMed  Google Scholar 

  19. Ramos E, Molina M, Sarria J, Perez-Moneo B, Burgos E, Lopez-Santamaria M, et al. Chronic rejection with sclerosing peritonitis following pediatric intestinal transplantation. Pediatr Transplant. 2007;11(8):937–41.

    Article  PubMed  Google Scholar 

  20. Macedo C, Sindhi R, Mazariegos GV, Abu-Elmagd K, Bond GJ, Reyes J. Sclerosing peritonitis after intestinal transplantation in children. Pediatr Transplant. 2005;9(2):187–91.

    Article  PubMed  Google Scholar 

  21. Ruiz P, Suarez M, Nishida S, de la Cruz V, Nicolas M, Weppler D, et al. Sclerosing mesenteritis in small bowel transplantation: possible manifestation of acute vascular rejection. Transplant Proc. 2003;35(8):3057–60.

    Article  CAS  PubMed  Google Scholar 

  22. Parizhskaya M, Redondo C, Demetris A, Jaffe R, Reyes J, Ruppert K, et al. Chronic rejection of small bowel grafts: pediatric and adult study of risk factors and morphologic progression. Pediatr Dev Pathol. 2003;6(3):240–50.

    Article  PubMed  Google Scholar 

  23. Lopez-Garcia P, Calvo Pulido J, Colina F, Jimenez-Romero C, Ibarrola de andres C, Lopez-Alonso G, et al. Histologic evaluation of organ preservation injury and correlation with cold ischemia time in 13 intestinal grafts. Transplant Proc. 2014;46(6):2096–8.

    Article  CAS  PubMed  Google Scholar 

  24. Lauro A, Bagni A, Zanfi C, Pellegrini S, Dazzi A, Del Gaudio M, et al. Mortality after steroid-resistant acute cellular rejection and chronic rejection episodes in adult intestinal transplants: report from a single center in induction/preconditioning era. Transplant Proc. 2013;45(5):2032–3.

    Article  CAS  PubMed  Google Scholar 

  25. Wu T, Abu-Elmagd K, Bond G, Nalesnik MA, Randhawa P, Demetris AJ. A schema for histologic grading of small intestine allograft acute rejection. Transplantation. 2003;75(8):1241–8.

    Article  PubMed  Google Scholar 

  26. Takahashi H, Kato T, Selvaggi G, Nishida S, Gaynor JJ, Delacruz V, et al. Subclinical rejection in the initial postoperative period in small intestinal transplantation: a negative influence on graft survival. Transplantation. 2007;84(6):689–96.

    Article  PubMed  Google Scholar 

  27. White FV, Reyes J, Jaffe R, Yunis EJ. Pathology of intestinal transplantation in children. Am J Surg Pathol. 1995;19(6):687–98.

    Article  CAS  PubMed  Google Scholar 

  28. Ruiz P, Bagni A, Brown R, Cortina G, Harpaz N, Magid MS, et al. Histological criteria for the identification of acute cellular rejection in human small bowel allografts: results of the pathology workshop at the VIII International Small Bowel Transplant Symposium. Transplant Proc. 2004;36(2):335–7.

    Article  CAS  PubMed  Google Scholar 

  29. Lee RG, Nakamura K, Tsamandas AC, Abu-Elmagd K, Furukawa H, Hutson WR, et al. Pathology of human intestinal transplantation. Gastroenterology. 1996;110(6):1820–34.

    Article  CAS  PubMed  Google Scholar 

  30. Liu L, Talmon G. Quantification of intraepithelial lymphocytes in normal pediatric small intestinal allograft and native ilea. Transplant Proc. 2011;43(5):1831–5.

    Article  CAS  PubMed  Google Scholar 

  31. Talmon G, El Behery R, Radio S, Fischer R, Shostrom V, Wisecarver J. Crypt apoptotic count reproducibility in small bowel allograft biopsies. Int J Surg Pathol. 2013;21(3):257–60.

    Article  PubMed  Google Scholar 

  32. Ruiz P, Weppler D, Nishida S, Kato T, Selvaggi G, Levi D, et al. International grading scheme for acute rejection in small bowel transplantation: implementation and experience at the University of Miami. Transplant Proc. 2006;38(6):1683–4.

    Article  CAS  PubMed  Google Scholar 

  33. Ruiz P, Takahashi H, Delacruz V, Island E, Selvaggi G, Nishida S, et al. International grading scheme for acute cellular rejection in small-bowel transplantation: single-center experience. Transplant Proc. 2010;42(1):47–53.

    Article  CAS  PubMed  Google Scholar 

  34. Pasternak BA, Collins MH, Tiao GM, Rudolph JA, Alonso MH, Ryckman FC, et al. Anatomic and histologic variability of epithelial apoptosis in small bowel transplants. Pediatr Transplant. 2010;14(1):72–6.

    Article  PubMed  Google Scholar 

  35. Sigurdsson L, Reyes J, Todo S, Putnam PE, Kocoshis SA. Anatomic variability of rejection in intestinal allografts after pediatric intestinal transplantation. J Pediatr Gastroenterol Nutr. 1998;27(4):403–6.

    Article  CAS  PubMed  Google Scholar 

  36. Nguyen T, Park JY, Scudiere JR, Montgomery E. Mycophenolic acid (cellcept and myofortic) induced injury of the upper GI tract. Am J Surg Pathol. 2009;33(9):1355–63.

    Article  PubMed  Google Scholar 

  37. Papadimitriou JC, Cangro CB, Lustberg A, Khaled A, Nogueira J, Wiland A, et al. Histologic features of mycophenolate mofetil-related colitis: a graft-versus-host disease-like pattern. Int J Surg Pathol. 2003;11(4):295–302.

    Article  PubMed  Google Scholar 

  38. Star KV, Ho VT, Wang HH, Odze RD. Histologic features in colon biopsies can discriminate mycophenolate from GVHD-induced colitis. Am J Surg Pathol. 2013;37(9):1319–28.

    Article  PubMed  Google Scholar 

  39. Ziring D, Tran R, Edelstein S, McDiarmid SV, Gajjar N, Cortina G, et al. Infectious enteritis after intestinal transplantation: incidence, timing, and outcome. Transplantation. 2005;79(6):702–9.

    Article  PubMed  Google Scholar 

  40. Eisengart LJ, Chou PM, Iyer K, Cohran V, Rajaram V. Rotavirus infection in small bowel transplant: a histologic comparison with acute cellular rejection. Pediatr Dev Pathol. 2009;12(2):85–8.

    Article  PubMed  Google Scholar 

  41. Adeyi OA, Costa G, Abu-Elmagd KM, Wu T. Rotavirus infection in adult small intestine allografts: a clinicopathological study of a cohort of 23 patients. Am J Transplant. 2010;10(12):2683–9.

    Article  CAS  PubMed  Google Scholar 

  42. Adeyi OA, Randhawa PA, Nalesnik MA, Ochoa ER, Abu-Elmagd KM, Demetris AJ, et al. Posttransplant adenoviral enteropathy in patients with small bowel transplantation. Arch Pathol Lab Med. 2008;132(4):703–5.

    PubMed  Google Scholar 

  43. Pinchoff RJ, Kaufman SS, Magid MS, Erdman DD, Gondolesi GE, Mendelson MH, et al. Adenovirus infection in pediatric small bowel transplantation recipients. Transplantation. 2003;76(1):183–9.

    Article  PubMed  Google Scholar 

  44. Kaufman SS, Magid MS, Tschernia A, LeLeiko NS, Fishbein TM. Discrimination between acute rejection and adenoviral enteritis in intestinal transplant recipients. Transplant Proc. 2002;34(3):943–5.

    Article  CAS  PubMed  Google Scholar 

  45. Parizhskaya M, Walpusk J, Mazariegos G, Jaffe R. Enteric adenovirus infection in pediatric small bowel transplant recipients. Pediatr Dev Pathol. 2001;4(2):122–8.

    Article  CAS  PubMed  Google Scholar 

  46. Morotti RA, Kaufman SS, Fishbein TM, Chatterjee NK, Fuschino ME, Morse DL, et al. Calicivirus infection in pediatric small intestine transplant recipients: pathological considerations. Hum Pathol. 2004;35(10):1236–40.

    Article  PubMed  Google Scholar 

  47. Ruiz P, Garcia M, Pappas P, Esquenazi V, Kato T, Mittal N, et al. Mucosal vascular alterations in the early posttransplant period of small bowel allograft recipients may reflect humoral-based allograft rejection. Transplant Proc. 2002;34(3):869–71.

    Article  CAS  PubMed  Google Scholar 

  48. Gonzalez-Pinto IM, Tzakis AG, Tsai HL, Chang JW, Tryphonopoulos P, Nishida S, et al. Association between panel reactive antibodies and acute small bowel rejection: analysis of a series of 324 intestinal transplants. Transplant Proc. 2010;42(10):4269–71.

    Article  CAS  PubMed  Google Scholar 

  49. Tsai HL, Island ER, Chang JW, Gonzalez-Pinto I, Tryphonopoulos P, Nishida S, et al. Association between donor-specific antibodies and acute rejection and resolution in small bowel and multivisceral transplantation. Transplantation. 2011;92(6):709–15.

    Article  CAS  PubMed  Google Scholar 

  50. Wu T, Abu-Elmagd K, Bond G, Demetris AJ. A clinicopathologic study of isolated intestinal allografts with preformed IgG lymphocytotoxic antibodies. Hum Pathol. 2004;35(11):1332–9.

    Article  CAS  PubMed  Google Scholar 

  51. Troxell ML, Higgins JP, Kambham N. Evaluation of C4d staining in liver and small intestine allografts. Arch Pathol Lab Med. 2006;130(10):1489–96.

    PubMed  Google Scholar 

  52. de Serre NP, Canioni D, Lacaille F, Talbotec C, Dion D, Brousse N, et al. Evaluation of c4d deposition and circulating antibody in small bowel transplantation. Am J Transplant. 2008;8(6):1290–6.

    Article  PubMed  Google Scholar 

  53. Tryphonopoulos P, Weppler D, Nishida S, Kato T, Levi D, Selvaggi G, et al. Mucosal fibrosis in intestinal transplant biopsies correlates positively with the development of chronic rejection. Transplant Proc. 2006;38(6):1685–6.

    Article  CAS  PubMed  Google Scholar 

  54. Harpaz N, Schiano T, Ruf AE, Shukla D, Tao Y, Fishbein TM, et al. Early and frequent histological recurrence of Crohn’s disease in small intestinal allografts. Transplantation. 2005;80(12):1667–70.

    Article  PubMed  Google Scholar 

  55. Desai CS, Khan K, Gruessner A, Gruessner R. Outcome of intestinal transplants for patients with Crohn’s disease. Transplant Proc. 2013;45(9):3356–60.

    Article  CAS  PubMed  Google Scholar 

  56. Sustento-Reodica N, Ruiz P, Rogers A, Viciana AL, Conn HO, Tzakis AG. Recurrent Crohn’s disease in transplanted bowel. Lancet. 1997;349(9053):688–91.

    Article  CAS  PubMed  Google Scholar 

  57. Reyes J, Green M, Bueno J, Jabbour N, Nalesnik M, Yunis E, et al. Epstein Barr virus associated posttransplant lymphoproliferative disease after intestinal transplantation. Transplant Proc. 1996;28(5):2768–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Abu-Elmagd KM, Mazariegos G, Costa G, Soltys K, Bond G, Sindhi R, et al. Lymphoproliferative disorders and de novo malignancies in intestinal and multivisceral recipients: improved outcomes with new outlooks. Transplantation. 2009;88(7):926–34.

    Article  PubMed  Google Scholar 

  59. Finn L, Reyes J, Bueno J, Yunis E. Epstein-Barr virus infections in children after transplantation of the small intestine. Am J Surg Pathol. 1998;22(3):299–309.

    Article  CAS  PubMed  Google Scholar 

  60. Jugie M, Canioni D, Le Bihan C, Sarnacki S, Revillon Y, Jan D, et al. Study of the impact of liver transplantation on the outcome of intestinal grafts in children. Transplantation. 2006;81(7):992–7.

    Article  PubMed  Google Scholar 

  61. Wu G, Selvaggi G, Nishida S, Moon J, Island E, Ruiz P, et al. Graft-versus-host disease after intestinal and multivisceral transplantation. Transplantation. 2011;91(2):219–24.

    Article  PubMed  Google Scholar 

  62. Talmon GA, Saigh QM, DiMaio D, Wisecarver JL, Radio SJ. Characterization of epithelial apoptosis in biopsies of small-bowel allografts using cleaved caspase 3 immunostaining. Int J Surg Pathol. 2010;18(6):482–7.

    PubMed  Google Scholar 

  63. Akpinar E, Vargas J, Kato T, Smith L, Hernandez E, Selvaggi G, et al. Fecal calprotectin level measurements in small bowel allograft monitoring: a pilot study. Transplantation. 2008;85(9):1281–6.

    Article  PubMed  Google Scholar 

  64. David AI, Selvaggi G, Ruiz P, Gaynor JJ, Tryphonopoulos P, Kleiner GI, et al. Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation. Transplantation. 2007;84(9):1077–81.

    Article  CAS  PubMed  Google Scholar 

  65. Ruiz P, Tryphonopoulos P, Island E, Selvaggi G, Nishida S, Moon J, et al. Citrulline evaluation in bowel transplantation. Transplant Proc. 2010;42(1):54–6.

    Article  CAS  PubMed  Google Scholar 

  66. Hibi T, Nishida S, Garcia J, Tryphonopoulos P, Tekin A, Selvaggi G, et al. Citrulline level is a potent indicator of acute rejection in the long term following pediatric intestinal/multivisceral transplantation. Am J Transplant. 2012;12 Suppl 4:S27–32.

    Article  PubMed  Google Scholar 

  67. Andreev VP, Tryphonopoulos P, Blomberg BB, Tsinoremas N, Weppler D, Neuman DR, et al. Peripheral blood gene expression analysis in intestinal transplantation: a feasibility study for detecting novel candidate biomarkers of graft rejection. Transplantation. 2011;92(12):1385–91.

    Article  PubMed  Google Scholar 

  68. Asaoka T, Island ER, Tryphonopoulos P, Selvaggi G, Moon J, Tekin A, et al. Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies. Transpl Int. 2011;24(7):697–707.

    Article  CAS  PubMed  Google Scholar 

  69. Asaoka T, Sotolongo B, Island ER, Tryphonopoulos P, Selvaggi G, Moon J, et al. MicroRNA signature of intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies. Am J Transplant. 2012;12(2):458–68.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Stanford University Medical Center, Stanford, CA, USA

    John P. Higgins M.D. & Neeraja Kambham M.D.

Authors
  1. John P. Higgins M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neeraja Kambham M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John P. Higgins M.D. .

Editor information

Editors and Affiliations

  1. Department of Pathology, McGill University and McGill University Health Center, Montreal, Québec, Canada

    René P. Michel

  2. Department of Pathology, Stanford University Medical Center, Stanford, California, USA

    Gerald J. Berry

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Higgins, J.P., Kambham, N. (2016). Intestinal Transplantation. In: Michel, R., Berry, G. (eds) Pathology of Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-29683-8_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-29683-8_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-29681-4

  • Online ISBN: 978-3-319-29683-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation