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Organ transplantation has quickly developed into a dynamic medical field involving a large multidisciplinary team to manage patients' care pre- and post-transplantation stages. One more recently developing field is multi-visceral transplantation (MVT) in the setting of intestinal failure and/or accompanying multisystem organ failure. This activity describes and reviews the role of the interprofessional team in evaluating and treating patients who undergo intestinal multi-visceral transplantation. Objectives: Assess the treatment considerations for patients with end-organ dysfunction requiring workup for transplantation. Identify the indications for multi-visceral transplantation. Evaluate the most common techniques for organ transplantation. Access free multiple choice questions on this topic.

Multivisceral transplantation (MVT) can be categorized into many different organ combinations. Still, this topic focuses on concurrent transplantation of the intestine, stomach, hepatobiliary system, and the pancreaticoduodenal complex – which can also be modified by “cherry-picking” different organs that suit the recipient’s condition. Some approach MVT by replacing any organ that relies on the superior mesenteric and celiac arteries. The concept of a total multi-visceral abdominal transplant was introduced in 1960 by the father of modern transplantation – Thomas Starzl.[1] Originally performed on dogs to study the effects of mass denervation of homografts, the concept was not abandoned, and in the 80s, it was attempted again, but this time on humans. Unfortunately, the first patient suffered post-operative hemorrhage; the following two developed posttransplant lymphoproliferative disorder (PTLD) and never left the hospital. The first hospital discharge MVT was performed in December of 1989. The patient was able to survive 10 months without parenteral support and ultimately passed from metastatic pancreatic cancer. Since 1988, 1,916 intestinal transplantations have been combined with other organs, most commonly the liver-intestine-pancreas (1,105), with the second most common being the liver-intestine (464). With advancements in immunosuppression and post-operative care, the 1-year survival rate has increased from approximately 40% to over 80% since the 1990s, with 5-year survival being around 60%.[2]

Rejection Considered to be the largest lymphoid organ, the small bowel creates a substantial lifelong challenge for managing both acute and chronic allograft rejection. The introduction of novel immunosuppression agents in the 1990s catapulted MVT into a viable armamentarium for patients. Graft survival did not significantly change after the introduction of cyclosporin A compared to the improvements seen in other solid organ transplants. It was not until the introduction of tacrolimus in the 1990s that patient outcomes and rejection rates improved.[13] Typical maintenance therapy includes tacrolimus, mycophenolate mofetil, and prednisone. Due to the vague clinical manifestation of rejection symptoms (increased stoma output, abdominal discomfort distension, and weight loss), routine surveillance of rejection is performed at planned intervals on an institutional basis. Histologic confirmation of rejection is considered the gold standard for diagnosis. The tissue is obtained through endoscopic transitional biopsies taken from multiple areas of the graft, with increased suspicion of rejection in ileal segments due to the increased amount of Peyer patches. Depending on the surgical approach, biopsies of the transplanted abdominal wall flap can provide a less invasive approach to the diagnosis of rejection. The development of laboratory screening has also played a role in the early recognition of rejection. Low serum citrulline levels and high fecal calprotectin are emerging as reliable, noninvasive measures of allograft rejection.[14][15] There also has been some data to suggest that combined liver-intestinal transplants, compared to intestinal transplantation alone, offer a benefit regarding the reduction of acute and chronic rejection.[16][17] Graft versus Host Disease (GVHD)

Histologic confirmation of rejection is considered the gold standard for diagnosis. The tissue is obtained through endoscopic transitional biopsies taken from multiple areas of the graft, with increased suspicion of rejection in ileal segments due to the increased amount of Peyer patches. Depending on the surgical approach, biopsies of the transplanted abdominal wall flap can provide a less invasive approach to the diagnosis of rejection. The development of laboratory screening has also played a role in the early recognition of rejection. Low serum citrulline levels and high fecal calprotectin are emerging as reliable, noninvasive measures of allograft rejection.[14][15] There also has been some data to suggest that combined liver-intestinal transplants, compared to intestinal transplantation alone, offer a benefit regarding the reduction of acute and chronic rejection.[16][17] Graft versus Host Disease (GVHD) Graft versus host disease occurs when donor cells recognize the host cells as foreign antigens and begin to mount a donor-mediated immune response against the recipient tissue. Along with the significant concerns of rejection in intestinal transplants, the amount of lymphoid tissue also creates concerns about the allograft assaulting the recipient. Thankfully, the incidence is relatively low (approximately 6%), but GVHD carries significant mortality, as high as 70%.[18]  Diagnosis is through polymerase chain reaction and immunohistologic staining. Treatment includes increasing immunomodulating drugs and even stem cell therapy.[19] Risk factors for GVHD include younger age and spleen in the en bloc transplantation. Although a single center reporting 100 MVTs did not see a statistically significant increase in GVHD when transplanting the spleen. Other solid organ transplantations have expressed a theoretical increase in GVHD when combined with a splenic transplant.[20] PTLD

Graft versus host disease occurs when donor cells recognize the host cells as foreign antigens and begin to mount a donor-mediated immune response against the recipient tissue. Along with the significant concerns of rejection in intestinal transplants, the amount of lymphoid tissue also creates concerns about the allograft assaulting the recipient. Thankfully, the incidence is relatively low (approximately 6%), but GVHD carries significant mortality, as high as 70%.[18]  Diagnosis is through polymerase chain reaction and immunohistologic staining. Treatment includes increasing immunomodulating drugs and even stem cell therapy.[19] Risk factors for GVHD include younger age and spleen in the en bloc transplantation. Although a single center reporting 100 MVTs did not see a statistically significant increase in GVHD when transplanting the spleen. Other solid organ transplantations have expressed a theoretical increase in GVHD when combined with a splenic transplant.[20] PTLD PTLD is a well-documented complication for many solid organ transplantations and should be briefly mentioned in this review of complications. While not classified as a single disease, it is more of a syndromic presentation that involves potentially neoplastic lymphocytic proliferation that can create a difficult and deadly presentation for post-transplant care. The growths are common in B lymphocyte origin, which is typically related to Epstein-Barr virus. Treatment includes reduction of immunosuppression and antiviral therapy, but this comes with the risk of graft failure secondary to rejection. The median time for development for one institution was 25.3 months, and all patients could recover clinically. There has been some data to suggest that the transplantation of the spleen could increase the incidence of PTLD.[21] Infections

PTLD is a well-documented complication for many solid organ transplantations and should be briefly mentioned in this review of complications. While not classified as a single disease, it is more of a syndromic presentation that involves potentially neoplastic lymphocytic proliferation that can create a difficult and deadly presentation for post-transplant care. The growths are common in B lymphocyte origin, which is typically related to Epstein-Barr virus. Treatment includes reduction of immunosuppression and antiviral therapy, but this comes with the risk of graft failure secondary to rejection. The median time for development for one institution was 25.3 months, and all patients could recover clinically. There has been some data to suggest that the transplantation of the spleen could increase the incidence of PTLD.[21] Infections Opportunistic infections, from bacterial to viral, are well-established as a necessary risk in all solid organ transplantations. Subjecting the body to immunosuppression medication opens the body up to life-threatening otherwise unremarkable infections in immunocompetent individuals. Some institutions make every effort to preserve the native spleen to prevent acquired asplenic opportunistic infections (from encapsulated bacteria) and attempt to reduce the incidence of asplenic sepsis. In the setting of MVT, cytomegalovirus is a clinically significant pathogen due tocytomegalovirus's higher tropism in gastrointestinal cells and the increased amount of potential cellular hosts (due to the increased lymphoid cells in the small bowel). In one study, up to 94% of MVT patients developed infections post-transplant.[22][23] Surgical Complications Post-surgical complications vary depending on the organs transplanted but tend to occur in the early post-transplant period. These can include anastomotic leaks, arterial and venous graft thrombosis, and bleeding. Some are managed non-operatively, but the most feared complication is arterial thrombus, creating an emergent relaparotomy. Unfortunately, the graft can often not be salvaged in this setting, and retransplantation may be required. Signs of arterial graft thrombosis are like that of acute mesenteric ischemia. In a single institution of 500 transplants, the arterial thrombosis incidence was 3.8%[24]

Multivisceral transplant combines the anatomy and physiology of multiple systems, requiring a robust and active multidisciplinary team. Each provider, from dietitian to therapist, plays a critical role in the profound improvement in the quality of life that MVT provides. Leading institutions have been more aggressive at transplanting earlier due to the life-changing improvements. Over the past three decades, patient outcomes have improved over two-fold – largely due to establishing a dedicated interdisciplinary team. The team must be proactive in following up with pre and post-transplant patients. Patients from lower socioeconomic environments and pediatric populations benefit from close surveillance; this improves compliance and early recognition of potential complications.[28]