Intestinal transplantation has shown exceptional growth over the past 10 years. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run.
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Intestinal transplantation has shown exceptional growth over the past 10 years. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies.
Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run.
Currently, intestinal transplantation is the only possibility of cure for patients with intestinal failure IF who have severe complications related to prolonged use of total parenteral nutrition TPN.
Intestinal transplantation may be isolated or in combination with other organs multivisceral. Intestinal and multivisceral transplantation is the least often performed surgical procedure when compared to other transplants of solid organs, and represents the greatest challenge in management.
There are still few accredited and capable centers in the world. In the United States, in , there were centers and, in , this number dropped to , and of these, only 18 performed more than 10 procedures a year. Over the last 5 to 10 years, intestinal and multivisceral transplantation has evolved in a manner similar to that of other transplants, starting from an experimental procedure and then moving on to a real therapeutic option.
IF happens due to the absorption deficiencies of the macro- and micronutrients, so that the daily requirements cannot be met by oral or enteral nutrition. However, intestinal and multivisceral transplantation became of victim of its own success, since due to the prolonged use of central venous catheters, many patients began to present with severe complications, such as infection, thrombosis, and cholestatic hepatic disease induced by TPN.
In Brazil, approximately people a year will be candidates for intestinal transplantation. Despite technological advances and clinical needs, there are no specialized reference centers in rehabilitation and intestinal and multivisceral transplantation in Brazil. Patients who present with large resections that result in less than cm of jejunum-ileum in addition to the loss of the ileocecal valve will certainly become dependent on TPN. The clinical progression of IF has a difficult prognosis, and is associated with a few risk factors that lead to the need for continuous use of parenteral nutrition.
This article had the objective of assessing the progression of intestinal and multivisceral transplantation and its current status. Intestinal and multivisceral transplantation was performed for the first time in dogs in by Lillehei et al. All the patients died and only one survived for more than 1 month. The negative results of these first transplants occurred due to technical and infectious complications and problems with conventional immunosuppression.
In , a 6-year-old child receiving prolonged TPN due to short bowel syndrome with end-stage hepatic disease induced by chronic TPN use was submitted to the first multivisceral transplant, but died hours after the transplant as a result of massive hemorrhage.
Lymphoproliferative disease was responsible for the death of these patients. In Canada, Grant et al. The appearance of tacrolimus, in , was a milestone in intestinal transplant. The medication resulted in improved integration of the graft and better survival rates. Since then, there have been various advances in intestinal and multivisceral transplantation.
The indication of transplantation as to the choice of organs to be used in grafting varies according to the underlying disease, that is, the presence or not of chronic liver disease, number of prior abdominal operations, as well as function and quality of other organs.
As to use of better nomenclature to define the techniques used in intestinal transplantation, literature has not been very consistent. The general consensus was that the terminology to be used would be a descriptive system in which two components would be used: first, if the transplant included the liver or not, and second, relative to the intestinal organs to be removed from the receptor.
However this was abandoned and replaced by monobloc transplantation of the intestines, liver, and pancreas referred to by various centers as the multivisceral or Omaha technique , since it avoids dissection of the hepatic hilus and of all the duodenum pancreatic complex. Some centers still associate other organs to the gastrointestinal tract, such as the stomach, duodenum, colon, and spleen.
One of the types of transplants is the isolated small bowel, indicated for patients with irreversible IF, in which only the small bowel is transplanted; usually patients with severe complications of parenteral nutrition, in the absence of severe liver disease. The multivisceral transplant covers the bloc transplant of the stomach, pancreaticoduodenal region, small bowel, liver with or without the colon and spleen.
It is indicated in irreversible IF, complicated by advanced liver failure demonstrated by clinical signs of cirrhosis or by histology consistent with chronic liver disease; and unresectable benign or low-grade malignant tumors, involving the mesentery, associated with hepatic metastases, in the absence of extra-abdominal disease; including desmoid and neuroendocrine tumors.
In the absence of hepatic metastases and celiac vascular involvement, the multivisceral transplant may be performed sparing the recipient liver modified multivisceral. For the neuroendocrine tumors, the evaluation of distant metastases should follow the previously established protocol for hepatic transplant, bearing in mind the need to exclude distant metastatic diseases. Diffuse thrombosis of the mesenteric-portal system and other non-classic indications should also be considered, such as abdominal catastrophes.
Vianna e Mangus demonstrated surprising results of survival in multivisceral transplants in patients with extensive mesenteric-portal thrombosis, who — to date — are contraindicated to have an isolated liver transplant.
Modified multivisceral transplant is a variation of the multivisceral transplant, in which the liver of the recipient is spared. Intestinal and multivisceral transplantation can be associated with the kidney transplantation in the presence of renal failure. Contraindications of the intestinal and multivisceral transplants follow the same applied to solid abdominal organs, such as severe cardiopulmonary disease, sepsis, aggressive malignant disease, and severe neurological damage.
HIV is considered a relative contraindication. Early overall survival of the patient and of the graft after intestinal transplant has shown a significant improvement over the last 10 years.
They observed that 24 patients presented with short bowel syndrome and required TPN, and that 5 of them had indications for intestinal transplantation as per international criteria. Of the patients with indication for transplantation, only two remained alive when the research was concluded. It is believed that the perfecting of the surgical technique, immune suppression with perioperative induction using anti-lymphocyte antibodies, control of viral infections, perfecting of the multidisciplinary team, rigorous selection of donors, effective clinical postoperative management, and advances in detection and treatment are factors related to satisfactory results.
Despite all these advances, sepsis is still the primary cause of mortality and is associated with the use of high doses of immune suppressors to counterbalance the high level of rejection. These drugs also contribute to the appearance of renal insufficiency and lymphoproliferative disease.
The graft versus host disease and the need for new surgical approaches are complications that contribute to the lack of success in intestinal and multivisceral transplantation. As is true with all transplants, this balance between infection and rejection should be more firmly managed in the case of intestinal and multivisceral transplants. Hospital readmission of these patients is more frequent in comparison with other transplants and is generally associated with infection, rejection, dehydration, and gastrointestinal complications.
The multivisceral transplant, on the other hand, has a lower rejection rate relative to isolated intestinal transplantation, due to the immune protection afforded by the liver. In , Hospital Israelita Albert Einstein conducted the first multivisceral transplant in Brazil in a patient with extensive portal-mesenteric thrombosis, due to chronic cryptogenic liver disease, portal hypertension, recurrent episodes of upper digestive hemorrhage, weekly paracentesis, and significant cachexia.
Length of hospital stay was 30 days, and death occurred in 8 months due to infection. Recently, the group did the second case in a patient with history of bariatric surgery and cirrhosis due to non-alcoholic steatohepatitis, with complex thrombosis of the portal mesenteric system. This patient presented with a good perioperative evolution, but progressed with graft versus host disease on the 16 th postoperative day, with no response to treatment, and died on the 34 th postoperative day.
It is known that extensive thrombosis of the entire portal mesenteric territory remains a great challenge to liver surgeons, in which the alternative techniques of solution for this problem show insignificant success rates, with high mortality and morbidity rates. Tzakis et al. Vianna et al. Brazil still needs a better approach for intestinal and multivisceral transplantation, with public health policies focused on the issue of this disease, with specialized teams within the Unified Healthcare System in intestinal rehabilitation.
Another point to be considered is the potential pediatric donors, since the pathologies that lead to intestinal and multivisceral transplants prevail in this population. O futuro do transplante de intestino e multivisceral parece promissor. Ainda existem poucos centros credenciados e habilitados no mundo. Grant et al. O surgimento do tacrolimus, em , foi um marco no transplante de intestino. National Center for Biotechnology Information , U.
Journal List Einstein Sao Paulo v. Einstein Sao Paulo. Find articles by Bianca Della Guardia. Find articles by Douglas Bastos Neves. Find articles by Fernando Luis Pandullo. Find articles by Lilian Amorim Curvelo. Find articles by Luiz Gustavo Guedes Diaz. Find articles by Marcela Balbo Rusi. Find articles by Marcelo de Melo Viveiros.
Find articles by Marcio Dias de Almeida. Find articles by Marina Gabrielle Epstein. Find articles by Pamella Tung Pedroso. Find articles by Paolo Salvalaggio. Find articles by Rodrigo Andrey Rocco. Find articles by Samira Scalso de Almeida. Find articles by Marcelo Bruno de Rezende. Author information Article notes Copyright and License information Disclaimer. Received May 5; Accepted Feb 8.
Copyright notice. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Intestinal transplantation has shown exceptional growth over the past 10 years. Chart 1 Indications approved by Medicare. Loss of two or more of the six primary central venous accesses jugular, subclavian, and femoral Episodes of catheter-associated infections, two or more per year, fungemia, shock, or adult respiratory distress syndrome Refractory hydroelectrolytic disorders Hepatic disease associated with TPN, reversible Growth and development deficit in children.
Open in a separate window. Chart 2 Non-approved indications by Medicare. Extensive mesenteric-portal thrombosis Abdominal catastrophes Low-grade malignant or benign tumors.
Current status of small bowel and multivisceral transplantation. Adv Surg. Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg. Small intestine transplantation.
U.S. Food and Drug Administration
Intestinal and multivisceral transplantation