Multivisceral Transplantation Research Articles

Nutritional outcomes following multi-visceral transplant: preliminary findings from the Cambridge intestinal transplantation unit

Nutritional outcomes following multi-visceral transplant: preliminary findings from the Cambridge intestinal transplantation unit

Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States.

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01). D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

Exploring the complexities of megacystis-microcolon-intestinal hypoperistalsis syndrome: insights from genetic studies.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is an uncommon genetic disorder inherited in an autosomal recessive pattern that affects the muscles that line the bladder and intestines. The most common genes associated with MMIHS mutations are ACTG2, LMOD1, MYH11, MYL9, MYLK, and PDCL3. However, the complete genetic landscape of MMIHS still needs to be fully understood. The diagnosis of MMIHS can be challenging. However, advances in prenatal and diagnostic techniques, such as ultrasound and fetal urine analysis, have improved the ability to detect the syndrome early. Targeted next-generation sequencing (NGS) and other diagnostic tests can also diagnose MMIHS. The management of MMIHS involves addressing severe intestinal dysmotility, which often necessitates total parenteral nutrition (TPN), which can lead to complications such as hepatotoxicity and nutritional deficiencies. Multivisceral and intestinal transplantation has emerged as therapeutic options, offering the potential for improved outcomes and enteral autonomy.Understanding the genetic underpinnings of MMIHS is crucial for personalized care. While the prognosis varies, timely interventions and careful monitoring enhance patient outcomes. Genetic studies have given us valuable insights into the molecular mechanisms of MMIHS. These studies have identified mutations in genes involved in the development and function of smooth muscle cells. They have also shown that MMIHS is associated with defects in the signaling pathways that control muscle contraction. Continued research in the genetics of MMIHS holds promise for unraveling the complexities of MMIHS and improving the lives of affected individuals.

Including the liver in the visceral allograft: Impact on donor-specific anti-HLA antibodies and long-term outcomes

Humoral immunity emerges as a risk factor for graft failure after visceral transplantation (VTx) and development of donor-specific anti-HLA antibodies (DSAs) has been linked with poor outcomes. In most cases, a simultaneous liver transplant can be safely performed in sensitized patients with DSA and appears protective against lymphocytotoxic antibodies. We investigated the incidence of acute (AR) and chronic rejection (CR) in 32 VTx without any B cell-depleting pre-treatment (6 isolated intestinal transplants (IT) and 26 liver-containing, multivisceral transplants (MVT) and assessed the presence of donor-specific antibodies (DSA) pre- and post-transplantation. Twenty-one patients (65 %) developed AR, 15 (57 %) of the MVT and 6 (100 %) of the IT (p = 0.05). CR occurred in 4 IT (60 %, p < 0.001). At one month, de novo DSA were present in 71 % of VTx (66 % MVT vs 100 % IT, p = 0.09). At the last available follow-up, 69 % of the MVT and 50 % of the IT patients were DSA-free. De novo DSA seemed more persistent (7/19, 37 %) than pre-Tx DSA (1/6, 17 %; p = n.s.), de novo DSA were more frequently specific for HLA class II than class I, 16/19 (84 %) vs. 7/19 (37 %; p = 0.003), and HLA-DQ was their most frequent target HLA. DQ mismatches appeared to be a risk factor for developing de novo DSA. In conclusion, liver-containing visceral allografts have superior short- and long-term outcomes compared with liver-free allografts. De novo DSA develop early and frequently after VTx performed without B cell-depleting induction therapy, but the exact role of DSA in the pathogenesis of rejection remains unclear.

Endovascular Treatment of a Multi-visceral Aortic Conduit Blowout With Parallel Stent Grafts and Coils.

Multi-visceral transplantation (MVT) is a complex surgical procedure involving the transplantation of multiple abdominal organs as a single unit, typically used as bailout treatment of patients with devastating abdominal pathologies. Due to the complexity of the procedure, major and even life-threatening complications can happen. Vascular complications, including anastomotic breakdowns or pseudoaneurysms due to infections, can be universally lethal. Open surgical repair is often not an option due to the hostile operative field. We report a case of endovascular salvage of multi-visceral aortic conduit blowout utilizing parallel stent grafts and coils without sacrifice of the transplanted viscera. This combination can successfully control bleeding and maintain graft perfusion in this rare but devastating complication.

Excess waitlist mortality among candidates for multivisceral liver-intestine transplant in acuity circle allocation

Candidates for multivisceral transplant (MVT) have experienced decreased access to transplant in recent years. Using Organ Procurement and Transplantation Network data, transplant and waiting list outcomes for MVT (ie, liver-intestine, liver-intestine-pancreas, and liver-intestine-kidney-pancreas) candidates listed between February 4, 2018, and February 3, 2022, were analyzed, including model for end-stage liver disease/pediatric end-stage liver disease and exception scores by era (before and after acuity circle [AC] implementation on February 4, 2020) and age group (pediatric and adult). Of 284 MVT waitlist registrations (45.6% pediatric), fewer had exception points at listing post-AC compared to pre-AC (10.0% vs 19.1%), and they were less likely to receive transplant (19.1% vs 35.9% at 90 days; 35.7% vs 57.2% at 1 year). Of 177 MVT recipients, exception points at transplant were more common post-AC compared to pre-AC (30.8% vs 20.2%). Postpolicy, adult MVT candidates were more likely to be removed due to death/too sick compared with liver-alone candidates (13.5% vs 5.6% at 90 days; 24.2% vs 9.8% at 1 year), whereas no excess waitlist mortality was observed among pediatric MVT candidates. Under current allocation policy, multivisceral candidates experience inferior waitlist outcomes compared with liver-alone candidates. Clarification of guidance around submission and approval of multivisceral exception requests may help improve their access to transplantation and achieve equity between multivisceral and liver-alone candidates on the liver transplant waiting list.

Treatment of Complex Desmoid Tumors in Familial Adenomatous Polyposis Syndrome by Intestinal Transplantation.

Desmoid tumors are fibroblastic lesions which often have an unpredictable and variable clinical course. In the context of familial adenomatous polyposis (FAP), these frequently occur intra-abdominally, especially in the small-bowel mesentery resulting in sepsis, fistulation, and invasion of the abdominal wall and retroperitoneum. In selected cases where other modalities have failed, the most radical option is to perform a total enterectomy and intestinal transplantation (ITx). In this study, we present our center's experience of ITx for desmoid in patients with FAP. We performed a retrospective review of our prospectively collected database between 2007 and 2022. All patients undergoing ITx for FAP-related desmoid were included. Between October 2007 and September 2023, 144 ITx were performed on 130 patients at our center. Of these, 15 patients (9%) were for desmoid associated with FAP (7 modified multivisceral transplants, 6 isolated ITx, and 2 liver-containing grafts). The median follow-up was 57 mo (8-119); 5-y patient survival was 82%, all with functioning grafts without local desmoid recurrence. These patients presented us with several complex surgical issues, such as loss of abdominal domain, retroperitoneal/abdominal wall involvement, ileoanal pouch-related issues, and the need for foregut resection because of adenomatous disease. ITx is a viable treatment in selected patients with FAP and extensive desmoid disease. The decision to refer for ITx can be challenging, particularly the timing and sequence of treatment (simultaneous versus sequential exenteration). Delays can result in additional disease burden, such as secondary liver disease or invasion of adjacent structures.

Timing and Complications of Intestinal Ostomy Takedown After Intestinal and Multivisceral Transplantation

Ileostomies are typically created at the time of intestinal and multivisceral transplantation to assist in graft monitoring with endoscopy and biopsies. Often, these ostomies are reversed with a takedown procedure once there is stable graft function, but data are limited on associated complications of the takedown procedure for patients with intestinal transplants. To assess complications associated with takedowns in this patient population, we performed a retrospective analysis of patients who had an intestinal transplant with elective ostomy takedown after transplant. No prisoners were used in the study and this manuscript is in compliance with the Helsinki Congress and the Declaration of Istanbul. A total of 16 patients, 10 isolated patients with intestinal transplants and 6 patients with multivisceral transplants, were included in the study, and takedown occurred at a mean of (236.8 ± 117.1) days after transplant. Of the 16 patients, 5 patients (31%) had uncomplicated courses after takedown with no infection, no rejection, and no hospital readmission within 3 months of takedown. The rest of the patients (69%) developed either infection or rejection within 3 months of takedown, and 1 patient died of infection after ileostomy takedown. This case series highlights the high risk of complications after ileostomy takedown for patients with intestinal transplants and contributes to the growing debate regarding the role of ileostomy creation and reversal in patients with intestinal transplants.

Risk Factors Associated with PTLD Related Mortality in Adult Multivisceral Transplant Recipients - A Single Centre Cohort Study.

Background: PTLD is a heterogeneous group of lymphoproliferative diseases which can add significant mortality following multivisceral transplantation (MVTx). Our study aimed to identify potential risk factors of mortality in adult MVTx recipients who developed PTLD. Methods: All adult recipients of intestinal-containing grafts transplanted in our institution between 2013 and 2022, and who developed PTLD, were included in the study. Results: PTLD-associated mortality was 28.6% (6/21). Increased relative risk of mortality was associated with Stage 3 ECOG performance score (p=0.005; HR 34.77; 95%CI 2.94-410.91), if the recipients had a splenectomy (p=0.036; HR 14.36; 95%CI 1.19-172.89), or required retransplantation (p=0.039; HR 11.23; 95% CI 1.13-112.12). There was a significant trend for increased risk of PTLD mortality with higher peak EBV load (p=0.008), longer time from MVTx to PTLD diagnosis (p=0.008), and higher donor age (p 0.001). Peak LDH before treatment commencement was significantly higher in the mortality group vs the survival group (520.3 +- 422.8 IU/L vs 321.8 +- 154.4 IU/L; HR 1.00, 95%CI 1.00 to 1.01, p=0.019). Peak viral load prior to treatment initiation (Cycle Threshold (CT) cutoff = 32) correlated with the relative risk of death in MVTx patients who developed PTLD [29.4 (3.5) CTs in survivors compared to 23.0 (4.0) CTs in the mortality group]. Conclusions: This is the first study to identify risk factors for PTLD-associated mortality in an adult MVTx recipient cohort. Validation in larger multicentre studies and subsequent risk stratification according to these risk factors may contribute to better survival in this group of patients.

Loss of α-smooth muscle actin immunostaining is not a useful marker for functional impairment: a comparison from patients with and without small bowel motility disorder

Abstract Introduction/Objective Prior studies have reported the loss α-smooth muscle actin (α-SMA) immunostaining in the inner circular layer of the muscularis propria in small bowel motility disorder cases, but this remains controversial with conflicting data. In this study we aimed to characterize the immunoreactivity of α-SMA expression in the muscularis propria of the small intestine, specifically jejunum, in patients with and without small bowel motility disorder. Methods/Case Report A total of 28 samples of transmural proximal jejunum biopsies from adult patients with small bowel motility disorder by manometric and/or radiologic testing and 47 control tissues were evaluated. The controls were full thickness, longitudinal tissue sections from segmental resections performed due to trauma from gunshot wound (n= 30), multi-visceral transplant for neoplasms (n= 4), liver failure with concurrent portal vein thrombosis (n= 9), and isolated intestinal transplant for Crohn disease (n= 4). Immunostaining for α-SMA was performed with appropriate controls to confirm the presence of staining in the circular and longitudinal muscle layers of the muscularis propria in each sample and recorded as retained or diminished. Results (if a Case Study enter NA) In the small bowel motility disorder and control cases, 43% (12/28) and 62% (29/47) of the cases showed no or minimal α-SMA expression in the inner circular layer with peripheral accentuation (p = 0.113), respectively. The remaining small bowel motility disorder cases (16/28, 57%) and the control group (18/47, 38%) showed retained expression of α-SMA in both layers of the muscularis propria. Conclusion Loss or diminished α-SMA expression in the inner circular layer of muscularis propria is present in similar frequency in cases with and without small bowel motility disorder and does not correlate with impairment of function.

Incidence, Management and Outcome of Post-Transplant Lymphoproliferative Disease after 5797 Solid-Organ Transplants over a 30-Year Period in a Single Hospital

Introduction: Post-transplant lymphoproliferative disorders (PTLD) are heterogenous lymphoproliferative disorders that develop because of immunosuppression in transplant recipients. Epstein-Barr Virus (EBV) infection is a major risk factor for the development of PTLD. Its management generally involves a reduction in immunosuppression and initial treatment with rituximab monotherapy (RM). Aim: To present the epidemiology, management, and outcomes of PTLD in a large unicentric Spanish cohort of solid organ transplant (SOT) recipient who were transplanted over a 30-year period. Methods: This is a retrospective study of 5797 SOT recipients who had their first transplant between 1992 and 2021 at Hospital Universitario 12 de Octubre. For each type of transplant, we calculated the incidence rate of PTLD. OS (Overall survival) was analyzed using the Kaplan-Meier model and the log-rank test Prognostic impact of the main clinical, analytical variables and prognostic indexes were analyzed. Results: With a median follow-up of 16.4 years, 105 of 5797 SOT developed a monomorphic or Hodking-like PTLD (1.8%). The incidence was: 10% multivisceral transplantation (MVT), 2.8% heart, 2.3% liver, 2.2% lung, 1.4% kidney and 1.3% simultaneous kidney-pancreas (SPK). Median age at transplant was 48.3 (1-89) years. 12 were pediatric recipients' (1 lung, 1 kidney, 10 liver). 72% were men. Histochemical stains for Epstein-Barr virus (EBV) were performed in 75 of 105 diagnoses. EBER-positive histology was observed in the majority of patients (n = 44/77, 57%). Median time from transplantation to PTLD was 6.7 (0-16.4) years (21% in the 1st year post-transplant). In EBER-positive the onset was earlier (3.2 vs 9.2 years; p: .004) with 36% arising the 1st year post-transplant. 5-years cumulative incidence was 10% in MTV compared to 0.18%-1.6% in the rest. With a median follow-up of 6.9 years; median OS was 79.5 months, with no difference between type of organ transplanted, era of transplant, EBER histology or time from transplant to PTLD. Using logistic regression, age, beta-2-microglobulin (B2M), as well as the IPI, modified R-IPI, NCCN-IPI and GELTAMO-IPI prognostic indices were found to be significant prognostic factors for OS ( Table 1). Interestingly, the highest OS stratification was observed with the modified R-IPI, showing a median OS not reached in the low-risk group, versus 38 months at high risk and 3.2 months at very high risk (p&amp;lt;0.001). Immunosuppression (IS) was switched as the 1st therapeutic aptitude in 57% of the patients. Median OS was not reached in patients with IS switch (n=41) (plateau at 10 years; estimated OS 56%) vs. 15.3m for patients without IS switch (n=39) (P: .004) ( Figure 1). IS was reduced in 80%. It also reached OS impact (P: .05). There were 89 monomorphic patients who were treated as follows: RM (n=22), R-Chemotherapy (n=37), chemotherapy (n=6), no treatment (n=7), unknown (n=16). Of the 22 RM patients, 9 (41%) achieved complete remission (CR) with RM and required no further treatment. In the R-Chemotherapy (n=37) group (70% R-CHOP), 26 (70%) reached CR. There was no significant difference in OS between the two groups. 8/22 (36%) died in the RM group (2/22 (9%) due progressive disease (PD), 2/22 (9%) died pre-remission of non-PTLD causes and 4/37 (18%) died in remission of unrelated causes). In the R-Chemo group 8/37 (48%) patients dead (4/37 (10%) patients died of PD, 6/37 (16%) died pre-remission of non-PTLD causes and 8/37 (22%) died in remission of unrelated causes). Conclusion: With this SOT cohort from a center with long experience we demonstrated an incidence of PTLD of 1.8%. EBV positive PTLD emerged sooner but OS was similar to those EBV negative. Stablished prognostic indices in DLBCL such as IPI, NCCN-IPI, and modified R-IPI were also applicable in PTLD. The modified R-IPI showed the best separation between the groups. Switch or reduction of the IS is an essential point to improve its prognosis. Our data suggest that first-line RM is an interesting option to consider. Strategies to tailor treatment with the least possible toxicity are necessary in these vulnerable patients. Additionally, our results suggest the utility of modified R-IPI in the clinical practice of PTLD and may serve as a basis for the development of specific prognostic models for this entity.

Surgical strategies to treat portal vein thrombosis during adult liver transplantation.

The incidence of portal vein thrombosis (PVT) at the time of liver transplantation (LT) may be variable and underestimated. Therefore, preoperative diagnosis and stratification of its extension is so relevant for adequate surgical planning. Revascularization of the portal vein graft becomes essential for graft and patient survival after LT. Early stages of PVT may be managed with eversion thrombectomy and end-to-end anastomoses. However, severe PVT (grades 3 and 4) poses significant challenges for patients requiring LT, resulting in more complex surgeries and higher complication rates. To address these complexities, various surgical techniques have been developed, including collateral alternative vessel utilization, renoportal anastomoses, mesoportal jump graft placement, cavoportal hemitranspositions, portal vein arterialization, or even multivisceral transplantation. We herein describe the preoperative surgical planning as well as the different surgical strategies possible to treat portal vein thrombosis during LT. A comprehensive preoperative evaluation of PVT is crucial for accurately assessing its extent and severity. This information is vital for proper surgical planning, which ultimately prepares both the surgeon and the patient for potentially complex procedures during LT. The surgical alternatives presented in this technical report offer promising solutions for treating PVT during LT, making it a viable option for selected patients.

Abstract P3013: Rare Case Of Catheter-related Right Atrial Thrombosis In A Pediatric Multi-visceral Transplant Patient

Introduction: There has been a recent increase in the use of intraoperative transesophageal echocardiography (TEE) in liver transplant surgeries to identify intracardiac thrombi and pulmonary embolism (PE). These are rare but serious complications of transplant surgery that carry a high mortality risk. However, there is a lack of literature supporting the use of TEE during liver transplants, especially in pediatric cases. Case Presentation: We present a rare case of intraoperative catheter-related right atrial thrombus (CRAT) in a nine-year-old multi-visceral transplant (MVT) patient. This patient’s medical history was notable for preterm birth and gastroschisis complicated by neonatal necrotizing enterocolitis resulting in short-gut syndrome. He had a significant surgical history, including intestinal resection, Hartmann Procedure, and cholecystectomy, after which he developed non-cholestatic liver disease. He was admitted for MVT for intestinal failure associated with ESLD. The procedure was complicated by massive hemorrhage during the dissection phase, significant coagulopathy after engrafting the donor liver, profound hemodynamic instability requiring inotropic drug support, and multiple instances of intraoperative CPR. Intraoperative TEE identified right atrial thrombi around the central venous line. The patient developed RV dysfunction and PEA secondary to PE on two occasions and received a total of 4 mg tissue plasminogen activator (tPA). In both cases, ROSC was achieved after thrombolysis. Due to profound coagulopathy and massive blood loss (70 liters), the completion of the surgery was postponed, and the patient left the operating room with an open abdomen. The patient’s postoperative course was complicated by hemodiafiltration, ureteral resection with reimplantation to bladder, pyloroplasty, appendectomy, small bowel resection, end colostomy and double-barrel ileostomy. The patient eventually developed a subarachnoid hemorrhage on POD3 and expired. Conclusion: This case highlights the importance of utilizing intraoperative TEE in pediatric liver transplant surgeries to diagnose intracardiac thrombi and PE.

Appendicitis to multivisceral transplantation: a career experience with appendiceal malignancy.

John Hunter is regarded as the father of scientific surgery. His principles involved reasoning, observation and experimentation. His most powerful saying was: "Why not try the experiment?" This manuscript charts a career in abdominal surgery ranging from the treatment of appendicitis to the development of the largest appendiceal tumour centre in the world. The journey has led to the first report of a successful multivisceral and abdominal wall transplant for patients with recurrent non-resectable pseudomyxoma peritonei. We all stand on the shoulders of giants and surgery progresses by learning from the past while being prepared to experiment into the future.

152: Painful hands in a multi visceral transplant patient

152: Painful hands in a multi visceral transplant patient

153: Eculizumab as a treatment for early antibody mediated liver rejection in a multivisceral transplant patient

153: Eculizumab as a treatment for early antibody mediated liver rejection in a multivisceral transplant patient

54: Immunological Aspects of Experimental Isolated intestinal and Modified Multivisceral Transplantation. Comparative Study.

54: Immunological Aspects of Experimental Isolated intestinal and Modified Multivisceral Transplantation. Comparative Study.

155: Modified multivisceral transplantation cured chronic intestinal pseudo-obstruction caused by rare autoimmune enteric leiomyositis:world’s first case report

155: Modified multivisceral transplantation cured chronic intestinal pseudo-obstruction caused by rare autoimmune enteric leiomyositis:world’s first case report

124: The first report of three-way macrochimerism in a patient receiving multivisceral transplantation following loss of an initial liver-intestine transplant

124: The first report of three-way macrochimerism in a patient receiving multivisceral transplantation following loss of an initial liver-intestine transplant

Clinical Utility of 18Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) in Multivisceral Transplant Patients.

Multivisceral transplant (MVTx) refers to a composite graft from a cadaveric donor, which often includes the liver, the pancreaticoduodenal complex, and small intestine transplanted en bloc. It remains rare and is performed in specialist centres. Post-transplant complications are reported at a higher rate in multivisceral transplants because of the high levels of immunosuppression used to prevent rejection of the highly immunogenic intestine. In this study, we analyzed the clinical utility of 28 18F-FDG PET/CT scans in 20 multivisceral transplant recipients in whom previous non-functional imaging was deemed clinically inconclusive. The results were compared with histopathological and clinical follow-up data. In our study, the accuracy of 18F-FDG PET/CT was determined as 66.7%, where a final diagnosis was confirmed clinically or via pathology. Of the 28 scans, 24 scans (85.7%) directly affected patient management, of which 9 were related to starting of new treatments and 6 resulted in an ongoing treatment or planned surgery being stopped. This study demonstrates that 18F-FDG PET/CT is a promising technique in identifying life-threatening pathologies in this complex group of patients. It would appear that 18F-FDG PET/CT has a good level of accuracy, including for those MVTx patients suffering from infection, post-transplant lymphoproliferative disease, and malignancy.