Intestinal transplantation and the European implication: impact of experience and study design

• Home parenteral nutrition
• intestinal transplantation
• candidacy
• outcome
• parenteral nutrition

Pironi et al recently published an article challenging current indications for intestinal transplantation (IT).1 The European home parenteral nutrition (HPN) database of 41 centres in nine countries was utilised and a 5-year prospective cross-sectional survey was conducted focusing on transplant candidacy with survival and causes of death as end points. With appreciation of the authors' scientific contribution, we felt obligated to highlight major flaws in the study design.

Identification of HPN patients who are candidates for transplant was the Achilles' heel of the study. Unfortunately, such determination, without formal listing, was based upon broad definitions and questionnaire data short of documented objective testing that is crucial to transplant candidacy.2 Another major concern is the small number of candidates who were actually transplanted (14.5%). In addition, limited centre experience in transplant versus HPN questioned the accuracy of data interpretation. Equally important is the proportionally small number of transplants that invalidates statistical comparison. Despite the appealing look of the term ‘pre-emptive/rehabilitative therapy’, the inclusion of ultra-short-bowel patients (47%) added more ambiguity with a wide variety of underlying disorders. Finally, the reported unexpected high 5-year survival (56%) among candidates who needed but never received ‘life-saving’ transplant and the overall relatively large percentage (∼50%) of the imprecise ‘other cause-related’ death category is a testimony of our critique.

IT is still in its infantile stage at most European centres as indicated by the reported overall small number (n=22) of transplants. Growing experience in surgical techniques and postoperative management is crucial for successful outcome.3 As admitted by the authors, disease gravity with no guideline protocols for referral or transplantation is another survival risk factor. Such experience would not be recognised by current Medicare policy despite the authors' adoption of its memorandum guidelines.4 During the same period and for the same indications, 182 patients received IT in Pittsburgh achieving 85% survival at 2 years and 75% survival at 5 years (figure 1A) with full nutritional autonomy in 90% of the patients. Superior results with survival calculated according to age were also reported in one of our recent publications quoted by the authors.5 Accordingly, with increasing experience, European centres could achieve similar outcomes.

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Figure 1

Cumulative survival of 182 patients who received intestinal transplantation (IT) between January 2004 and December 2008 at the University of Pittsburgh Medical Center: (A) total population; (B) according to type of allograft.

The authors acknowledged IT as rescue therapy for patients with HPN-related liver failure and those with mesenteric desmoids despite a respective mortality of 57% and 100%, respectively. The reported cumulative 2-year survival of 19% compared with 54% at 5 years for those who remained on HPN should cause concern over recommendation for IT in these patients. In 182 Pittsburgh-matched recipients, hepatic failure was the indication for liver-contained visceral transplant in 78 patients (43%) with 2- and 5-year survival of 81% and 70%, respectively (figure 1B). With desmoids (n=12), 5-year survival was 100%. In our total experience with 25 desmoid-related transplants, HPN failure, rather than the tumour itself, was the leading indication (76%) for IT.

The authors suggested a moratorium on IT for catheter-related complications and ultra-short-bowel pending the outcome of comprehensive cost-utility studies. The recommendation was based upon failure to demonstrate superior survival with IT. However, other significant therapeutic advantages including restoration of nutritional autonomy and related quality-of-life issues were not addressed. In a similar Pittsburgh cohort with slightly higher survival, nutritional autonomy was achievable in 92% of the patients. Universal adoption of the authors' proposed policy may victimise some patients with inadvertent development of irreversible HPN-associated complications including liver failure with increased mortality on candidate waiting list (figure 2).

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Figure 2

Waiting list death rates for candidates who need a liver allograft versus those who need liver-contained visceral allograft based on all adult liver candidates on the Organ Procurement and Transplantation Network (OPTN) waiting list between 2008 and 2009. Data presented to the OPTN/UNOS Liver and Intestinal Organ Transplantation Committee on 7 December 2010.

Until the availability of better-controlled or prospective randomised studies, IT should continue to be the appropriate rescue therapy for patients who no longer can be safely maintained on HPN. Meanwhile, a multidisciplinary team approach is mandatory for optimal management with prompt delivery of the appropriate therapeutic modality.