Skip to main content

Advertisement

SpringerLink
Log in

A meta-analysis of clinical outcome of intestinal transplantation in patients with total intestinal aganglionosis

  • Original Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

Aim of the study

Total intestinal aganglionosis (TIA) occurs in less than 1% of patients with Hirschsprung disease (HD), and TIA is the most severe form of HD. Survival has improved with the advent of parenteral nutrition and intestinal transplantation (ITx). The field of ITx has rapidly progressed in the last two decades and has now become an established treatment for patients with intestinal failure. The purpose of this meta-analysis was to determine the clinical outcome of ITx in patients with TIA.

Methods

A systematic literature search for relevant articles was performed in four databases using the combinations of the following terms: “total intestinal aganglionosis”, “intestinal transplantation”, and “Hirschsprung disease/Hirschsprung’s disease” for studies published between 2003 and 2016. The relevant cohorts of ITx in patients with TIA were systematically searched for clinical outcomes.

Main results

Thirteen studies met defined inclusion criteria, reporting a total of 63 patients who underwent ITx for TIA. Majority of patients were males (71.0%), and median age of ITx was 4.3 (range 0.25–17.6) years. Isolated ITx was performed in 37% patients and multivisceral ITx in 63%. Mean follow-up period was 40 months (range 1–154). Overall survival rate was 66%; the longest survivor was 12.8-year-old after ITx.

Conclusion

ITx appears promising in the management of TIA. ITx can be considered a feasible treatment option for patients with TIA who suffer from life-threatening complications of intestinal failure.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Caniano DA, Ormsbee HS 3rd, Polito W, Sun CC, Barone FC, Hill JL (1985) Total intestinal aganglionosis. J Pediatr Surg 20(4):456–460

    Article  CAS  PubMed  Google Scholar 

  2. MacKinnon AE, Cohen SJ (1977) Total intestinal aganglionosis. An autosomal recessive condition? Arch Dis Child 52(11):898–899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Talwalker VC (1976) Aganglionosis of the entire bowel. J Pediatr Surg 11(2):213–216

    Article  CAS  PubMed  Google Scholar 

  4. Coran AG, Teitelbaum DH (2000) Recent advances in the management of Hirschsprung’s disease. Am J Surg 180(5):382–387

    Article  CAS  PubMed  Google Scholar 

  5. Solari V, Ennis S, Yoneda A, Wong L, Messineo A, Hollwarth ME, Green A, Puri P (2003) Mutation analysis of the RET gene in total intestinal aganglionosis by wave DNA fragment analysis system. J Pediatr Surg 38(3):497–501. doi:10.1053/jpsu.2003.50087

    Article  CAS  PubMed  Google Scholar 

  6. Rudin C, Jenny PM, Fliegel CP, Ohnacker H, Heitz PU (1986) Zuelzer–Wilson’s syndrome and absence of the enteric nervous system. Two rare forms of anomalies of the enteric nervous system with identical clinical symptoms. Z Kinderchir 41(5):287–292. doi:10.1055/s-2008-1043361

    CAS  PubMed  Google Scholar 

  7. Rudin C, Jenny P, Ohnacker H, Heitz PU (1986) Absence of the enteric nervous system in the newborn: presentation of three patients and review of the literature. J Pediatr Surg 21(4):313–318

    Article  CAS  PubMed  Google Scholar 

  8. Sauvat F, Grimaldi C, Lacaille F, Ruemmele F, Dupic L, Bourdaud N, Fusaro F, Colomb V, Jan D, Cezard JP, Aigrain Y, Revillon Y, Goulet O (2008) Intestinal transplantation for total intestinal aganglionosis: a series of 12 consecutive children. J Pediatr Surg 43(10):1833–1838. doi:10.1016/j.jpedsurg.2008.03.028

    Article  PubMed  Google Scholar 

  9. Sigurdsson L, Reyes J, Kocoshis SA, Mazariegos G, Abu-Elmagd KM, Bueno J, Di Lorenzo C (1999) Intestinal transplantation in children with chronic intestinal pseudo-obstruction. Gut 45(4):570–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rovera GM, Schoen RE, Goldbach B, Janson D, Bond G, Rakela J, Graham TO, O’Keefe S, Abu-Elmagd K (2003) Intestinal and multivisceral transplantation: dynamics of nutritional management and functional autonomy. JPEN J Parenter Enter Nutr 27(4):252–259. doi:10.1177/0148607103027004252

    Article  Google Scholar 

  11. Bond GJ, Reyes JD (2004) Intestinal transplantation for total/near-total aganglionosis and intestinal pseudo-obstruction. Semin Pediatr Surg 13(4):286–292

    Article  PubMed  Google Scholar 

  12. Fouquet V, De Lagausie P, Faure C, Bloch J, Malbezin S, Ferkhadji L, Bauman C, Aigrain Y (2002) Do prognostic factors exist for total colonic aganglionosis with ileal involvement? J Pediatr Surg 37(1):71–75

    Article  CAS  PubMed  Google Scholar 

  13. Kleinhaus S, Boley SJ, Sheran M, Sieber WK (1979) Hirschsprung’s disease—a survey of the members of the Surgical Section of the American Academy of Pediatrics. J Pediatr Surg 14(5):588–597

    Article  CAS  PubMed  Google Scholar 

  14. Ikeda K, Goto S (1984) Diagnosis and treatment of Hirschsprung’s disease in Japan. An analysis of 1628 patients. Ann Surg 199(4):400–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tatekawa Y, Muraji T, Takamizawa S (2007) A case report of a patient with near total intestinal aganglionosis followed by the role of extended myectomy and synbiotics therapy. J Pediatr Surg 42(4):E9–12. doi:10.1016/j.jpedsurg.2007.01.058

    Article  PubMed  Google Scholar 

  16. Goulet O, Ruemmele F (2006) Causes and management of intestinal failure in children. Gastroenterology 130(2 Suppl 1):S16–S28. doi:10.1053/j.gastro.2005.12.002

    Article  CAS  PubMed  Google Scholar 

  17. Fortuna RS, Weber TR, Tracy TF Jr, Silen ML, Cradock TV (1996) Critical analysis of the operative treatment of Hirschsprung’s disease. Arch Surg 131(5):520–524 (discussion -524–525)

    Article  CAS  PubMed  Google Scholar 

  18. Marty TL, Seo T, Matlak ME, Sullivan JJ, Black RE, Johnson DG (1995) Gastrointestinal function after surgical correction of Hirschsprung’s disease: long-term follow-up in 135 patients. J Pediatr Surg 30(5):655–658

    Article  CAS  PubMed  Google Scholar 

  19. Ziegler MM, Royal RE, Brandt J, Drasnin J, Martin LW (1993) Extended myectomy–myotomy. A therapeutic alternative for total intestinal aganglionosis. Ann Surg 218(4):504–509 (discussion 509–511)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Saxton ML, Ein SH, Hoehner J, Kim PC (2000) Near-total intestinal aganglionosis: long-term follow-up of a morbid condition. J Pediatr Surg 35(5):669–672. doi:10.1053/jpsu.2000.5939

    Article  CAS  PubMed  Google Scholar 

  21. Shimotake T, Go S, Tomiyama H, Aoi S, Iwai N (2002) Proximal jejunostomy with or without myectomy–myotomy modification in five infants with total intestinal aganglionosis: an experience with surgical treatments in a single institution. J Pediatr Surg 37(6):835–839

    Article  PubMed  Google Scholar 

  22. Ziegler MM, Ross AJ 3rd, Bishop HC (1987) Total intestinal aganglionosis: a new technique for prolonged survival. J Pediatr Surg 22(1):82–83

    Article  CAS  PubMed  Google Scholar 

  23. Nwoye UO, Chaudhry QL, Mercer DF, Wendy GJ, Botha J, Langnas AN (2010) Experience of intestinal transplantation for total intestinal aganglionosis in children. Am J Transplant 4:379

    Google Scholar 

  24. Mannan AASR, Ko HM, Harpaz N (2016) Tu1865 post-transplant lymphoproliferative disorder in small bowel transplant recipients: a single center experience. Gastroenterology 150(4):S963. doi:10.1016/s0016-5085(16)33259-0

    Article  Google Scholar 

  25. Chardot C, Irtan S, Dupic L, Telion C, Moulin F, Zahar J, Canioni D, Lambot K, Charbit M, Boutemy A, Talbotec C, Colomb V, Goulet O, Aigrain Y, Revillon Y, Lacaille F (2011) Evolution of intestinal transplantation–multivisceral transplantation. JPGN 52:1

    Google Scholar 

  26. Sharif K, Beath SV, Kelly DA, McKiernan P, van Mourik I, Mirza D, Mayer AD, Buckels JA, de Ville de Goyet J (2003) New perspective for the management of near-total or total intestinal aganglionosis in infants. J Pediatr Surg 38(1):25–28. doi:10.1053/jpsu.2003.50004 (discussion 25–28)

    Article  CAS  PubMed  Google Scholar 

  27. Pakarinen MP, Kurvinen A, Koivusalo AI, Ruuska T, Makisalo H, Jalanko H, Rintala RJ (2013) Surgical treatment and outcomes of severe pediatric intestinal motility disorders requiring parenteral nutrition. J Pediatr Surg 48(2):333–338. doi:10.1016/j.jpedsurg.2012.11.010

    Article  PubMed  Google Scholar 

  28. Varkey J, Simren M, Jalanko H, Oltean M, Saalman R, Gudjonsdottir A, Gabel M, Borg H, Edenholm M, Bentdal O, Husby S, Staun M, Makisalo H, Bosaeus I, Olausson M, Pakarinen M, Herlenius G (2015) Fifteen years’ experience of intestinal and multivisceral transplantation in the Nordic countries. Scand J Gastroenterol 50(3):278–290. doi:10.3109/00365521.2014.999255

    Article  PubMed  Google Scholar 

  29. Chang HK, Kim SY, Kim JI, Kim SI, Whang JK, Choi JY, Park JM, Jung ES, Rha SE, Kim DG, Moon IS, Lee MD (2016) Ten-year experience with bowel transplantation at Seoul St. Mary’s Hospital. Transplant Proc 48(2):473–478. doi:10.1016/j.transproceed.2015.12.065

    Article  CAS  PubMed  Google Scholar 

  30. Ganousse-Mazeron S, Lacaille F, Colomb-Jung V, Talbotec C, Ruemmele F, Sauvat F, Chardot C, Canioni D, Jan D, Revillon Y, Goulet O (2015) Assessment and outcome of children with intestinal failure referred for intestinal transplantation. Clin Nutr 34(3):428–435. doi:10.1016/j.clnu.2014.04.015

    Article  CAS  PubMed  Google Scholar 

  31. Hukkinen M, Koivusalo A, Merras-Salmio L, Rintala RJ, Pakarinen MP (2015) Postoperative outcome and survival in relation to small intestinal involvement of total colonic aganglionosis. J Pediatr Surg 50(11):1859–1864. doi:10.1016/j.jpedsurg.2015.05.017

    Article  PubMed  Google Scholar 

  32. Neuvonen MI, Kyrklund K, Lindahl HG, Koivusalo AI, Rintala RJ, Pakarinen MP (2015) A population-based, complete follow-up of 146 consecutive patients after transanal mucosectomy for Hirschsprung disease. J Pediatr Surg 50(10):1653–1658. doi:10.1016/j.jpedsurg.2015.02.006

    Article  PubMed  Google Scholar 

  33. Ramisch D, Rumbo C, Echevarria C, Moulin L, Niveyro S, Orce G, Crivelli A, Martinez MI, Chavez L, Paez MA, Trentadue J, Klein F, Fernandez A, Solar H, Gondolesi GE (2016) Long-term outcomes of intestinal and multivisceral transplantation at a single center in Argentina. Transplant Proc 48(2):457–462. doi:10.1016/j.transproceed.2015.12.066

    Article  CAS  PubMed  Google Scholar 

  34. Ruttenstock E, Puri P (2009) A meta-analysis of clinical outcome in patients with total intestinal aganglionosis. Pediatr Surg Int 25(10):833–839. doi:10.1007/s00383-009-2439-2

    Article  PubMed  Google Scholar 

  35. Puri P (2011) Hirschsprung’s disease. In: Puri P (ed) Newborn surgery, 3rd edn. Hodder Arnold, London, pp 554–565

    Chapter  Google Scholar 

  36. Avitzur Y, Grant D (2010) Intestine transplantation in children: update 2010. Pediatr Clin North Am 57(2):415–431. doi:10.1016/j.pcl.2010.01.019 (table of contents)

    Article  PubMed  Google Scholar 

  37. Guarino A, De Marco G, Italian National Network for Pediatric Intestinal F (2003) Natural history of intestinal failure, investigated through a national network-based approach. J Pediatr Gastroenterol Nutr 37(2):136–141

    Article  PubMed  Google Scholar 

  38. Gupte GL, Beath SV, Protheroe S, Murphy MS, Davies P, Sharif K, McKiernan PJ, de Ville de Goyet J, Booth IW, Kelly DA (2007) Improved outcome of referrals for intestinal transplantation in the UK. Arch Dis Child 92(2):147–152. doi:10.1136/adc.2005.090068

    Article  PubMed  PubMed Central  Google Scholar 

  39. Mencin A, Kluwe J, Schwabe RF (2009) Toll-like receptors as targets in chronic liver diseases. Gut 58(5):704–720. doi:10.1136/gut.2008.156307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yang L, Seki E (2012) Toll-like receptors in liver fibrosis: cellular crosstalk and mechanisms. Front Physiol 3:138. doi:10.3389/fphys.2012.00138

    CAS  PubMed  PubMed Central  Google Scholar 

  41. El Kasmi KC, Anderson AL, Devereaux MW, Fillon SA, Harris JK, Lovell MA, Finegold MJ, Sokol RJ (2012) Toll-like receptor 4-dependent Kupffer cell activation and liver injury in a novel mouse model of parenteral nutrition and intestinal injury. Hepatology 55(5):1518–1528. doi:10.1002/hep.25500

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kaufman SS (2001) Small bowel transplantation: selection criteria, operative techniques, advances in specific immunosuppression, prognosis. Curr Opin Pediatr 13(5):425–428

    Article  CAS  PubMed  Google Scholar 

  43. Fishbein TM, Florman S, Gondolesi G, Schiano T, LeLeiko N, Tschernia A, Kaufman S (2002) Intestinal transplantation before and after the introduction of sirolimus. Transplantation 73(10):1538–1542

    Article  CAS  PubMed  Google Scholar 

  44. Pearce RJ, Pota H, Evehe MS, el Ba H, Mombo-Ngoma G, Malisa AL, Ord R, Inojosa W, Matondo A, Diallo DA, Mbacham W, van den Broek IV, Swarthout TD, Getachew A, Dejene S, Grobusch MP, Njie F, Dunyo S, Kweku M, Owusu-Agyei S, Chandramohan D, Bonnet M, Guthmann JP, Clarke S, Barnes KI, Streat E, Katokele ST, Uusiku P, Agboghoroma CO, Elegba OY, Cisse B, Ie AE, Giha HA, Kachur SP, Lynch C, Rwakimari JB, Chanda P, Hawela M, Sharp B, Naidoo I, Roper C (2009) Multiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria. PLoS Med 6(4):e1000055. doi:10.1371/journal.pmed.1000055

    Article  PubMed  PubMed Central  Google Scholar 

  45. Smith JM, Skeans MA, Horslen SP, Edwards EB, Harper AM, Snyder JJ, Israni AK, Kasiske BL (2017) OPTN/SRTR 2015 annual data report: intestine. Am J Transplant 17(Suppl 1):252–285. doi:10.1111/ajt.14127

    Article  PubMed  Google Scholar 

  46. Abu-Elmagd KM, Costa G, Bond GJ, Soltys K, Sindhi R, Wu T, Koritsky DA, Schuster B, Martin L, Cruz RJ, Murase N, Zeevi A, Irish W, Ayyash MO, Matarese L, Humar A, Mazariegos G (2009) Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg 250(4):567–581. doi:10.1097/SLA.0b013e3181b67725

    PubMed  Google Scholar 

  47. Abu-Elmagd KM, Costa G, Bond GJ, Wu T, Murase N, Zeevi A, Simmons R, Soltys K, Sindhi R, Stein W, Demetris A, Mazariegos G (2009) Evolution of the immunosuppressive strategies for the intestinal and multivisceral recipients with special reference to allograft immunity and achievement of partial tolerance. Transpl Int 22(1):96–109. doi:10.1111/j.1432-2277.2008.00785.x

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Children’s Research Centre, Our Lady’s Children’s Hospital, Dublin, Ireland

    Hiroki Nakamura & Prem Puri

  2. Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland

    Davina Henderson

  3. School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland

    Prem Puri

Authors
  1. Hiroki Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Davina Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prem Puri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroki Nakamura.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakamura, H., Henderson, D. & Puri, P. A meta-analysis of clinical outcome of intestinal transplantation in patients with total intestinal aganglionosis. Pediatr Surg Int 33, 837–841 (2017). https://doi.org/10.1007/s00383-017-4107-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00383-017-4107-2

Keywords

Search

Navigation