Small-Bowel Transplantation: Experimental and Clinical Fundamentals

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Usually the programs developed in the institutions where there was a well-established liver transplant programs with a large number of cases. Between and , just 28 Intestinal Transplant Centers worldwide reported to the Intestinal Transplant Registry, performing intestinal transplants in patients Despite the initial pioneering, Brazil remained for many years without a well- established program.

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There are some recent reports, but with no success The intestinal failure is clinical condition characterized by reduced functional capacity of the gastrointestinal tract to maintain digestion, absorption of nutrients and fluids needed for maintenance in adults, and or to the growth and development in children It is a result of major resections, trauma and enterocytes diseases may be an association of these manifestations. Many diseases do not cause loss of function itself, but require multiple bowel resections in its natural history. The most frequent causes are necrotizing enterocolitis, gastroschisis, intestinal atresia, volvulus, and Hirchsprung disease aganglionosis.

Among adults, mesenteric ischemia, inflammatory diseases, actinic enteritis, trauma and tumors are the most common causes Currently the failure of parenteral nutritional therapy, ie, patients who experience complications are candidates for SBT. Complications more accepted as indications are: thrombosis of two of the six major venous accesses; liver disease; episodes of catheter-related infections two or more per year, fungemia, shock or respiratory failure ; alterations of growth and development in children and refractory electrolyte changes In multivisceral transplantation, there are other indications: abdominal catastrophes, benign or malignant tumors of low grade, spindle mesenteric thrombosis and diffuse mesenteric portal thrombosis Abdominal catastrophes include chronic debilitating situations caused by abdominal trauma, severe acute pancreatitis, extensive intestinal resection and multiple abdominal interventions, leading to short bowel syndrome, multiples enterocutaneous fistulas, intestinal obstruction or chronic diffuse mesenteric vascular thrombosis.

Complete replacement of all organs of the abdominal cavity multivisceral transplantation may be the only alternative to reestablish normal physiology Complex portal venous thrombosis system may also be indication for multivisceral transplantation.

The situation most commonly involved in this context is liver transplantation with portal vein thrombosis. In the past, the presence of portal vein thrombosis in candidates for liver transplantation has been contraindication to the procedure. It has important technical difficulties and higher mortality. The alternatives for portal revascularization of the liver graft can be simply removing the thrombus undergoing or a graft to the superior mesenteric vein or varicose veins.

In grade IV thrombosis, portal arterialization, graft renal vein and cavoportal hemi-transposition 39 are alternatives to allow the organ vascularization, without decompressing the portal territory. The multivisceral transplantation has been proposed as an alternative to complex portal mesenteric system thrombosis, even in the absence of liver or intestinal failure A variety of tumors can involve the celiac axis and mesenteric root.

Neuroendocrine tumors and pancreatic adenocarcinoma and desmoid tumors are examples. Resection is sometimes risky or impossible without compromising the vascularity of the abdominal viscera. The isolated intestine transplantation, including autograft and multivisceral have been proposed as alternatives to these situations Because of early and severe recurrence in carcinomas, transplantation for desmoid tumors and well-differentiated neuroendocrine has been more accept However, patient populations are small and improvement of selection criteria is needed.

Patients dependent on parenteral nutrition without complications are not candidates for intestinal transplantation, nowadays. There are reports of patients on parenteral nutrition for many years. However, their quality of life is questioned, besides the high cost of nutrition maintenance. Studies evaluating the quality of life before and after the transplant, with validated questionnaires showed improvements in various aspects, including anxiety, depression and self-image There are no controlled studies comparing parenteral nutrition with SBT.

Selecting the type of graft.

The SBT can involves some others abdominal organs to be transplanted with the small intestine. The selection of organs to be included will depend on the underlying disease, quality of other abdominal organs, presence and severity of liver disease and the number of previous abdominal surgeries. The isolated small bowel graft Figure 1 is indicated in the presence of irreversible intestinal failure in the absence of severe hepatic dysfunction.

The determination of liver disease severity and reversibility is held more securely by liver biopsy. The presence of bridging fibrosis or cirrhosis indicates the necessity of replacement of the liver. Study showed an association between the levels of bilirubin, platelet count and albumin level in the presence of liver failure in children in parenteral nutrition The arterial anastomosis is established through the superior mesenteric artery graft to the aorta. The venous drainage is made through the superior mesenteric vein to the inferior vena cava or the mesenteric portal system.

Another study showed no difference in survival, however, the cumulative incidence of episodes of infection by bacteria of the gastrointestinal tract was higher in patients with systemic drainage, suggesting a protective role liver 6. In all modes is performed an ileostomy for endoscopic surveillance, facilitating the diagnosis of rejection and perfusion disorders. In the presence of irreversible liver disease, the liver should be included in the graft. This group of patients competes for scarce liver grafts.

Enhancement of allocation models and early referral to SBT can be a solution to this problem. The grafts can be deployed separately, or in a more convenient block. To maintain the liver and intestine block, it is necessary to include the pancreatoduodenal arc graft Figure 2. This avoids the dissection of biliary duct and portal vein, which can be difficult in small children. The arterial supply is established through an arterial graft to the aorta. Venous drainage is made through the hepatic veins to the inferior vena cava, as the mode of liver transplantation.

Venous drainage of the remaining viscera went to a shunt to the inferior vena cava or portal system. Failure of multiple abdominal organs, the graft to be employed is the multivisceral Figure 3. It is necessary a complete evisceration of the abdominal cavity.

Book Small Bowel Transplantation Experimental And Clinical Fundamentals

Multiorgan recipient receives in block: stomach, duodenum, pancreas, small intestine and liver. The arterial supply is established through the superior mesenteric artery and celiac trunk graft through a conduit to the aorta and venous drainage through the hepatic veins to the inferior vena cava. The gut is restored by anastomosing the esophagus or gastric reminiscent with the stomach graft. In the modified multivisceral transplantation Figure 4 , the recipient's liver is maintained.

He receives in block: stomach, duodenum, pancreas and small intestine. Funcional disorders of the digestive tract such as intestinal pseudo-obstruction or inflammatory diseases such as Crohn's may be indications. The arterial, and continuity of the digestive tract, are established as in multivisceral transplantation.

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The venous drainage is through the portal vein. Controversies exist regarding the inclusion of the colon and spleen grafts, the inclusion of colonic segments not added any morbidity, but only brought benefits continence in pediatric patients In relation to the spleen, in the same study group, tended to immunologic benefit, without altering the incidence of graft versus host disease Donor, procurement and preservation of grafts. The selection of grafts from deceased donors is following similar liver criteria with some changes Ideal donors are preferably younger and with little or no vasoactive drugs.

Preference is given to ABO identity. With the development of effective drugs for prophylaxis and treatment of cytomegalovirus seropositive donors are accepted, avoiding only for receivers with negative serology. Decontamination of the gastrointestinal tract and use of antibodies in donor lymphocytes showed no benefits related to infection, rejection episodes or incidences of graft versus host disease. Typically donors are also liver and pancreas grafts. Facing the bloodstream shared the simultaneous harvesting of these grafts can be a challenge, but is possible to perform the procedure without compromising the graft 1.

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The University of Wisconsin solution has been considered the gold standard for preservation of organs of the digestive system, no different to the intestine. However, there are reports of the use of other solutions, Celsior 30 and HTK SBT results are similar to University of Wisconsin solution for ischemic periods up to 8 h. Postoperative management and complications. Postoperatively, in addition to surgical complications bleeding, fistula, dehiscence and wound infection may occur episodes of rejection, opportunistic infections and nutritional rehabilitation.

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  5. The biggest obstacle to intestinal transplantation is graft rejection. It is the main factor in morbidity and mortality. Rejection has a negative impact on survival of graft Several strategies and immunosuppressive regimens irradiation graft infusion of donor bone marrow cells were utilized without impact 3. Best results were obtained with induction therapy with anti-lymphocyte antibodies, monoclonal or polyclonal, being used in most centers 3,14,29, The most commonly used drugs for induction are thymoglobulin, alemtuzumab, basiliximab and daclizumab.

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    As in the other abdominal organs transplants, corticosteroids are also used, and removed in accordance with the type of grafts and preferably each center. The crossmatch may help in individualizing immunosuppression. The diagnosis of acute cellular rejection is performed by clinical, endoscopic and pathologic anatomy.

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    In the presence of acute cellular rejection patients are very symptomatic, with fever, abdominal pain, vomiting, swelling of the stoma and gastrointestinal bleeding. The commitment starts at the terminal ileum. The routine ileostomy facilitates endoscopic assessment and biopsies. The endoscopic surveillance, with a magnification of x, is held two to three times per week in the first three months, being held once a month from then and according to the situation The closure of the ileostomy varies by center and type of transplant liver grafts with or without , being held from three to 12 months A number of endoscopic findings may be associated with acute rejection: mucosal erythema, congestion, shortening and flattening of the villi, friability and ulcerations The gold standard for the diagnosis of acute cellular rejection is histology.

    Small-Bowel Transplantation: Experimental and Clinical Fundamentals

    On suspicion of rejection several biopsies should be performed because the lesion can spare a few segments. A study conducted with the evaluation of approximately 3, biopsies 49 identified four main parameters related to rejection, allowing quantitative or semi-analysis, and can be easily identified by pathologists: architectural distortion, intestinal crypt epithelial injury, the number of apoptosis and crypt infiltration by lymphocytes in the lamina propria.

    The differential diagnosis should be done with opportunistic infections cytomegalovirus, adenovirus , lymphoproliferative disorders and other enteric diseases. As histology, rejection can be classified into indeterminate, mild, moderate or severe.