Abstract
Introduction
Multivisceral transplantation includes the simultaneous transplantation of multiple abdominal viscera including the stomach, duodenum, pancreas, and small intestine, with (multivisceral transplant, MVT) or without the liver (modified MVT, MMVT). This study reviews the changing indications and outcomes for this procedure over a 7-year period at a university medical center.
Methods
This study is a retrospective case review of MVTs performed between 2004 and 2010 at a single center. All cases were either MVT or MMVT and included a simultaneous kidney transplant, if indicated. Graft failure was defined as loss of the graft or complete loss of function. Graft function was monitored by clinical function, laboratory values, and serial endoscopy with biopsy.
Results
During the study period, 95 patients received 100 transplants including 84 MVT and 16 MMVT. There were 19 patients who received a simultaneous kidney graft. There were 24 pediatric and 76 adult recipients (range 7 months to 66 years). Indications included intestinal failure alone, intestinal failure with cirrhosis, complete portal mesenteric thrombosis, slow-growing central abdominal tumors, intestinal pseudoobstruction, and frozen abdomen. All patients received antibody-based induction immunosuppression with calcineurin inhibitor-based maintenance immunosuppression. At a median mortality adjusted follow-up of 25 months, 1- and 3-year patient survival is 72 % and 57 %. There was a learning curve with this complex procedure resulting in a 48 % patient survival during the period from 2004 to 2007, followed by a 70 % patient survival during the period from 2008 to 2010. Post-transplant complications included rejection (50 % MMVT and 17 % MVT), infection (>90 % first year), graft versus host disease (13 %), and post-transplant lymphoproliferative disorder (5 %).
Conclusion
Indications for MVT and MMVT have broadened to include patients with terminal conditions not amenable to other medical therapies such as slow-growing tumors of the mesenteric root, complete portomesenteric thrombosis, and abdominal catastrophes/frozen abdomen. Outcomes have improved over time with many patients returning to full functional status and enjoying long-term survival.
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Discussant
Dr. Ellen J. Hagopian (Neptune, NJ): Dr. Mangus' and his colleagues' work is of great importance in multivisceral organ transplantation. Today, as we continually attempt to expand indications for all organ transplantations, close scrutiny of the results are of utmost importance in order to justify proper allocation of organs. I have four questions regarding your data.
How do you further explain the improvement in survival in each of the three groups: adult MVT, adult MMVT, and pediatric MVT? This might be attributed to a number of things over the two time periods outside of the operative learning curve. Is the improvement in both graft and patient survival attributed to only operative technique, or are there other factors such as immunosuppression regimen changes or better patient selection?
Furthermore, you have demonstrated that those with renal failure and who undergo kidney transplant at the time of MVT have a poorer outcome. To what do you attribute this result? Have you looked at associated comorbidities that may increase the risk of death in this group?
What are the causes of graft losses and patient deaths in each group? To what do you attribute the difference between the graft and patient survival in each group, but in particular, in the pediatric MVT group in the latter time period?
Lastly, you have reported a relatively low rate of PTLD, in particular, in the pediatric MVT where the rate is typically higher. How do you explain this low rate? How many patients lost their grafts as a result of PTLD? How many patients were lost as a result of PTLD? Were any patients retransplanted, and what are your indications for retransplantation?
Thank you for the privilege to review your work.
Closing discussant
Dr. Richard S. Mangus: The learning curve in multivisceral transplantation is particularly steep for reasons which are multifactorial. The surgery itself is long and complex and requires meticulous planning from a multidisciplinary team including surgery and anesthesia, but also extending to the blood bank, organ procurement organization, intensive care unit, and the ancillary staff. Therefore, improved results at our center were the result of a combined effort with improvement in surgical technique, patient selection and management, and post-transplant care. Our results demonstrate a decreased survival with older recipients and those with renal failure, and we have more carefully scrutinized these patients in recent years.
The presence of renal failure is associated with worse clinical outcomes in most surgical scenarios from repair of a ruptured abdominal aortic aneurysm to severe trauma. These patients are more debilitated, require more active fluid and electrolyte management, and often have cardiovascular comorbidities. Intraoperatively, patients with renal failure are more likely to become coagulopathic which can lead to hemodynamic instability. Pressor use in the post-transplant period negatively affects the renal graft, and a transplant kidney may experience delayed graft function requiring further dialysis.
The primary cause of graft loss for all groups is rejection—both acute and chronic. We had no graft losses to vascular or surgical complications. The most concerning comorbidity in multivisceral patients is coronary artery disease or poor cardiac function, and we have a low threshold for excluding these patients. The primary cause of death for all groups is sepsis. Intestinal transplant patients require more immunosuppression compared to other transplants because of their high rate of graft rejection. To combat the risk of rejection, these patients receive greater immunosuppression, with the trade-off being a higher risk of infection. Intestinal transplant patients may have a compromised intestinal mucosa, particularly in the setting of rejection, which can result in ongoing translocation of bacteria from the intestinal tract to the blood stream. This increases the risk of infection at all sites from in-dwelling catheters to intraabdominal abscesses to the urine and lungs. Also, most intestinal transplant patients are malnourished, increasing their risk of wound infection and delaying tissue healing. Pediatric patients in this study achieved an excellent survival in the later years. Though they suffer from all the issues mentioned previously, the children are more able to withstand bouts of sepsis and rejection when compared to adults because of better cardiopulmonary reserve. We hypothesize that the particularly young children (<12 months of age) may be more tolerant to the multivisceral graft (from infant donors) because of the relatively immature immune system, and we see less rejection in this group.
Post-transplant lymphoproliferative disorder (PTLD) is well described in intestinal transplant patients and is felt to be related to the high level of immunosuppression. We have seen PTLD, but the cases have been limited and many have responded well to conventional oncologic therapy, and a decrease in immunosuppression. In this cohort of multivisceral patients, there were two cases of PTLD and neither case resulted in death. Overall, we have seen eight cases of PTLD in 175 intestinal transplant patients, with three resulting in death. The liver is protective against intestinal rejection in liver inclusive multivisceral transplantation, so in these patients, we lower immunosuppression more rapidly after the post-transplant induction period. This lower level of overall immunosuppression in patients with a transplant liver likely provides a relative protection for these transplant recipients compared to intestine alone or modified multivisceral patients who run higher levels of immunosuppression. Lower immunosuppression levels in the liver-inclusive patients may then result in less infection, renal insufficiency, PTLD, and cancer, though larger numbers would be required to demonstrate this statistically.
There were ten patients in this study who had undergone a previous transplant, two had received a previous liver transplant and eight had previously undergone intestinal transplant. To date, eight of these ten are alive (80 %). Indications for retransplant for these patients included intestinal failure (previous graft loss, n = 8) and portomesenteric thrombosis after previous liver transplant (n = 2).
This paper was presented as a plenary talk at Digestive Disease Week, May, 2012, San Diego, CA, USA.
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Mangus, R.S., Tector, A.J., Kubal, C.A. et al. Multivisceral Transplantation: Expanding Indications and Improving Outcomes. J Gastrointest Surg 17, 179–187 (2013). https://doi.org/10.1007/s11605-012-2047-7
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DOI: https://doi.org/10.1007/s11605-012-2047-7