- Email: [email protected]
Closure and Summary of Ninth International Small Bowel Transplantation Symposium
Closure and Summary of Ninth International Small Bowel Transplantation Symposium S.V. Beath ABSTRACT The highlights of The Ninth International Small Bowel Transplantation Symposium included the latest results from the Intestinal Transplant Registry (ITR), which demonstrated that the number of transplants performed annually continued to rise to 180 per year, most of which were performed in the United States, where the greatest number of home parenteral nutrition (PN) patients live (a prevalence of around 40 per million or 10,000 individuals). The three largest programs in the United States all use anti-CD25 monoclonal antibodies, but three different forms of lymphocyte depletion are employed in induction protocols: (1) humanized monoclonal anti-thymocyte globulin; (2) pretreatment of the recipient with Campath; (3) pretreatment of the small bowel allograft with antilymphocyte globulin. The main gain in these new approaches has been in the reduction in tacrolimus and steroid exposure. Indeed, the Pittsburgh team reduced tacrolimus to alternateday dosing and stopped steroids altogether at 6 months in some patients, recording 100% survival in the past 2 years. The ITR demonstration of a difference in survival between adult patients who are hospitalized (40% to 60%) versus those who are still at home (80% to 100% survival) when called to transplant makes it almost unethical to delay evaluating patients for small bowel transplantation once they start experiencing complications on home PN. The input of gastroenterologists is also crucial in making recommendations about isolated liver transplantation for individuals with a potential to come off PN. Several important papers with useful prognostic clinical data with respect to selecting patients for isolated liver transplant were presented. It is evident from demographic surveys that only 2% to 5% adult patients and 5% to 15% children in large, well-resourced PN programs will be unlucky enough to develop life-threatening complications, but they must have rapid access to small bowel transplantation in this event. It is therefore important that the collaboration between gastroenterologists and the intestinal transplant teams continues. These excellent results for small bowel transplantation mean that the time is right for a large cost-effectiveness study comparing small bowel transplantation with PN.
T
HIS NINTH INTERNATIONAL Small Bowel Transplantation Symposium has been significant for a number of reasons. It is clear that there are now: vastly improved pharmacological means to manage early rejection, better timing in referral of patients for transplant, as well as much wider recognition of the valuable work of multidisciplinary teams before and after transplant. Small bowel transplantation is now accepted as not only lifesaving, but life enhancing. The fact that small bowel transplantation is coming of age as an entity, is reflected in the need for a formal structure under the auspices of The Transplantation Society to represent the progress achieved and plan future developments. Our recently formed society, known as the Intestinal Transplant Associa-
tion, has elected its first President Andreas Tsakis and David Grant as the President-elect. David Grant reported the latest results of the Intestinal Transplant Registry to the delegates, showing an increased number of individuals transplanted each year, presently at around 180 per year. It is notable that the greatest numbers of transplants are taking place in The United States, where the greatest number of home parenteral nutrition (PN) From the Birmingham Childrens’ Hospital, West Midlands, UK. Address reprint requests to Dr S.V. Beath, Longacre House, New End, Hemingby, Nr Horncastle, Lincolnshire LN9 5QQ, UK. E-mail: [email protected]
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.05.032
Transplantation Proceedings, 38, 1657–1658 (2006)
1657
1658
patients live, namely, a prevalence of around 40 per million or 10,000 individuals. This finding of course is due to intestinal transplantation being complementary to home PN for the treatment of chronic intestinal failure. Historically Europe has been behind the United States in small bowel transplant activity, but one of the notable highlights of this symposium has been the contributions from centers in Italy, Spain, Germany, and the United Kingdom, where after a slow start in the 1990s, they have achieved successes comparable to those in the United States, Canada and France. Although small bowel transplantation has previously been regarded as a treatment of last resort in the management of intestinal failure, it has become clear from analyses by the Intestinal Transplant Registry that far better results are achieved when patients are transplanted as they start to deteriorate on home PN, rather than when they have established liver disease with frank jaundice and compromised venous access. Indeed, the difference in survival between adult patients who are hospitalized (40% to 60%) versus those who are still at home (80% to 100% survival) when called to transplantation, makes it almost unethical to delay evaluating patients for small bowel transplantation once they start experiencing complications on home PN. The work of multidisciplinary teams is crucial in any home PN program. It is not surprising that patients and families still require a lot of support after small bowel transplant. Even though the need for intravenous nutrition has been removed, patients require physical and psychological rehabilitation and support with practical problems, such as managing a stoma and organizing monitoring tests to evaluate the health of the small bowel allograft in a timely fashion. One of the important principles established at the Ninth International Small Bowel Transplantation Symposium was a Pre-Congress workshop for nurses, dieticians, physiotherapists, psychologists, and others, where the topics discussed included pretransplant assessment, discharge planning, rehabilitation, and growth posttransplant. It is further evidence of the maturation of small bowel transplant programs worldwide that this sort of forum is needed. The presence of so many representatives from small bowel multidisciplinary teams enhanced the overall conference, providing much grounded commentary on the proceedings and many pertinent questions from the floor. The Ninth International Small Bowel Transplantation Symposium was also notable for reports of major scientific advances. It was challenging to discover that the three largest programs in the United States (Pittsburgh, Nebraska, and Miami) have distinctly different approaches to induction of graft tolerance and maintenance immunosuppression. Yet all three reported improving survival rates. All three programs include lymphocyte depletion in their induction protocols, but by different means: (1) administering humanized monoclonal anti-thymocyte globulin; (2) pretreatment of the recipient with Campath; (3) pretreatment of the small bowel allograft with anti-lymphocyte globulin. In addition, a common theme is the use of anti-CD25 monoclonal antibodies (eg, basiliximab and
BEATH
daclizumab), which temporarily inhibit clonal expansion of cytotoxic T cells by blocking interleukin-2 receptors. The main gain in these new approaches is the reduction in tacrolimus and steroid exposure; indeed the team running the Pittsburgh program seek to reduce tacrolimus to alternate-day dosing and to stop steroids altogether at 6 months for some patients, recording 100% survival in the past 2 years. There was a strong gastroenterology presence at the symposium with excellent contributions from Andre van Gossum on how to maintain home PN patients in stable condition, especially those challenging ones with metabolic and fluid balance crises. Alan Buchman addressed the particular difficulties of identifying and managing cirrhotic patients awaiting intestinal organs. Olivier Goulet described how to deal with rapid intestinal transit in short gut patients before and after transplantation. The input of gastroenterologists is crucial in making recommendations about isolated liver transplantation for individuals (especially children less than 5 years old) with a potential to come off PN, because of the capacity of the intestine to adapt. There were several important papers from Los Angeles, Nebraska, and Birmingham demonstrating the value of multidisciplinary teams and providing clinical data with useful prognostic significance with respect to selecting patients for isolated liver transplantation. It is evident from demographic surveys that only 2% to 5% adult patients and 5% to 15% children in large and wellresourced parenteral nutrition programs will be unlucky enough to develop life-threatening complications. However, it is vital that they have rapid access to small bowel transplantation when this occurs. Therefore collaboration between gastroenterologists and the intestinal transplant teams must continue and expand. Although small bowel transplantation is maturing as a therapy, the pioneering spirit remains with new ideas about tolerance, blocking reperfusion injury, anti-tumor necrosis factor to manage steroid resistant rejection and the recognition of new patterns of pathology, for example, graftversus-host disease and chronic inflammation of the small bowel allograft. We must continue to cooperate to develop our knowledge by supporting the Intestinal Transplant Registry, lobbying our own health organizations to fund and support national registries for intestinal failure and working to optimize referral patterns and equitable access to comprehensive care for patients with intestinal failure. The excellent results for small bowel transplantation achieved in centers such Pittsburgh, Omaha, and Miami mean that the time is right for a cost-effectiveness study comparing small bowel transplantation with PN in hospitalized as well as home PN patients. Finally we must thank one of the most skilled and innovative surgeons in the field of small bowel transplantation, Jean de Ville de Goyet, and his excellent secretary Cathy Vuylsteke, for organizing a superb conference. We look forward to The Tenth International Small Bowel Transplantation Symposium in 2007 in Los Angeles being organised by Doug Farmer.
T
HIS NINTH INTERNATIONAL Small Bowel Transplantation Symposium has been significant for a number of reasons. It is clear that there are now: vastly improved pharmacological means to manage early rejection, better timing in referral of patients for transplant, as well as much wider recognition of the valuable work of multidisciplinary teams before and after transplant. Small bowel transplantation is now accepted as not only lifesaving, but life enhancing. The fact that small bowel transplantation is coming of age as an entity, is reflected in the need for a formal structure under the auspices of The Transplantation Society to represent the progress achieved and plan future developments. Our recently formed society, known as the Intestinal Transplant Associa-
tion, has elected its first President Andreas Tsakis and David Grant as the President-elect. David Grant reported the latest results of the Intestinal Transplant Registry to the delegates, showing an increased number of individuals transplanted each year, presently at around 180 per year. It is notable that the greatest numbers of transplants are taking place in The United States, where the greatest number of home parenteral nutrition (PN) From the Birmingham Childrens’ Hospital, West Midlands, UK. Address reprint requests to Dr S.V. Beath, Longacre House, New End, Hemingby, Nr Horncastle, Lincolnshire LN9 5QQ, UK. E-mail: [email protected]
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.05.032
Transplantation Proceedings, 38, 1657–1658 (2006)
1657
1658
patients live, namely, a prevalence of around 40 per million or 10,000 individuals. This finding of course is due to intestinal transplantation being complementary to home PN for the treatment of chronic intestinal failure. Historically Europe has been behind the United States in small bowel transplant activity, but one of the notable highlights of this symposium has been the contributions from centers in Italy, Spain, Germany, and the United Kingdom, where after a slow start in the 1990s, they have achieved successes comparable to those in the United States, Canada and France. Although small bowel transplantation has previously been regarded as a treatment of last resort in the management of intestinal failure, it has become clear from analyses by the Intestinal Transplant Registry that far better results are achieved when patients are transplanted as they start to deteriorate on home PN, rather than when they have established liver disease with frank jaundice and compromised venous access. Indeed, the difference in survival between adult patients who are hospitalized (40% to 60%) versus those who are still at home (80% to 100% survival) when called to transplantation, makes it almost unethical to delay evaluating patients for small bowel transplantation once they start experiencing complications on home PN. The work of multidisciplinary teams is crucial in any home PN program. It is not surprising that patients and families still require a lot of support after small bowel transplant. Even though the need for intravenous nutrition has been removed, patients require physical and psychological rehabilitation and support with practical problems, such as managing a stoma and organizing monitoring tests to evaluate the health of the small bowel allograft in a timely fashion. One of the important principles established at the Ninth International Small Bowel Transplantation Symposium was a Pre-Congress workshop for nurses, dieticians, physiotherapists, psychologists, and others, where the topics discussed included pretransplant assessment, discharge planning, rehabilitation, and growth posttransplant. It is further evidence of the maturation of small bowel transplant programs worldwide that this sort of forum is needed. The presence of so many representatives from small bowel multidisciplinary teams enhanced the overall conference, providing much grounded commentary on the proceedings and many pertinent questions from the floor. The Ninth International Small Bowel Transplantation Symposium was also notable for reports of major scientific advances. It was challenging to discover that the three largest programs in the United States (Pittsburgh, Nebraska, and Miami) have distinctly different approaches to induction of graft tolerance and maintenance immunosuppression. Yet all three reported improving survival rates. All three programs include lymphocyte depletion in their induction protocols, but by different means: (1) administering humanized monoclonal anti-thymocyte globulin; (2) pretreatment of the recipient with Campath; (3) pretreatment of the small bowel allograft with anti-lymphocyte globulin. In addition, a common theme is the use of anti-CD25 monoclonal antibodies (eg, basiliximab and
BEATH
daclizumab), which temporarily inhibit clonal expansion of cytotoxic T cells by blocking interleukin-2 receptors. The main gain in these new approaches is the reduction in tacrolimus and steroid exposure; indeed the team running the Pittsburgh program seek to reduce tacrolimus to alternate-day dosing and to stop steroids altogether at 6 months for some patients, recording 100% survival in the past 2 years. There was a strong gastroenterology presence at the symposium with excellent contributions from Andre van Gossum on how to maintain home PN patients in stable condition, especially those challenging ones with metabolic and fluid balance crises. Alan Buchman addressed the particular difficulties of identifying and managing cirrhotic patients awaiting intestinal organs. Olivier Goulet described how to deal with rapid intestinal transit in short gut patients before and after transplantation. The input of gastroenterologists is crucial in making recommendations about isolated liver transplantation for individuals (especially children less than 5 years old) with a potential to come off PN, because of the capacity of the intestine to adapt. There were several important papers from Los Angeles, Nebraska, and Birmingham demonstrating the value of multidisciplinary teams and providing clinical data with useful prognostic significance with respect to selecting patients for isolated liver transplantation. It is evident from demographic surveys that only 2% to 5% adult patients and 5% to 15% children in large and wellresourced parenteral nutrition programs will be unlucky enough to develop life-threatening complications. However, it is vital that they have rapid access to small bowel transplantation when this occurs. Therefore collaboration between gastroenterologists and the intestinal transplant teams must continue and expand. Although small bowel transplantation is maturing as a therapy, the pioneering spirit remains with new ideas about tolerance, blocking reperfusion injury, anti-tumor necrosis factor to manage steroid resistant rejection and the recognition of new patterns of pathology, for example, graftversus-host disease and chronic inflammation of the small bowel allograft. We must continue to cooperate to develop our knowledge by supporting the Intestinal Transplant Registry, lobbying our own health organizations to fund and support national registries for intestinal failure and working to optimize referral patterns and equitable access to comprehensive care for patients with intestinal failure. The excellent results for small bowel transplantation achieved in centers such Pittsburgh, Omaha, and Miami mean that the time is right for a cost-effectiveness study comparing small bowel transplantation with PN in hospitalized as well as home PN patients. Finally we must thank one of the most skilled and innovative surgeons in the field of small bowel transplantation, Jean de Ville de Goyet, and his excellent secretary Cathy Vuylsteke, for organizing a superb conference. We look forward to The Tenth International Small Bowel Transplantation Symposium in 2007 in Los Angeles being organised by Doug Farmer.