Intestinal Transplantation: Include the Spleen with Intestinal Graft?

The traditional procedure for multivisceral transplant (MVT) is to transplant the stomach, pancreas, intestine, and liver en bloc. During surgery, the native spleen is routinely removed from the recipient, and it usually creates more space in the abdomen to insert the allogeneic graft. Thus, recipients often become asplenic after MVT. Considering all of the risks and benefits, we advocate that temporary transplant of the donor spleen could be the best option for MVT recipients; it could potentially reduce the rate of intestinal allograft rejection without increasing the risk for graft-versus-host disease.

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.

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.

Primary Neuroendocrine Tumor of the Liver With Papillary Features in a Multivisceral Transplant Patient.

Primary neuroendocrine tumors (NETs) of the liver are rare and difficult to distinguish from other liver tumors such as cholangiocarcinoma and hepatocellular carcinoma. The patient was initially diagnosed with a NET of the liver in 2007. However, the origin of the cancer was not clear, that is, whether it was primary or originated from the gastrointestinal tract. Although the patient underwent partial hepatectomy, he suffered hepatic artery injury, resulting in biliary strictures. The patient eventually became untreatable and developed cirrhosis, a frozen abdomen. He received multivisceral transplantation in May 2019 and received the liver, duodenal-pancreatic complex, spleen, small bowel, and right colon. After the transplantation, the patient did well overall. More recently, he presented with food poisoning and underwent evaluation, and was found to have a mass in the liver. The liver mass was biopsied and revealed a poorly differentiated primary NET (grade 2) with ciliated papillary structures.

Bloodstream infections among intestinal and multivisceral transplant recipients.

OBJECTIVE: To examine the etiologies, risk factors, and microbiology of bloodstream infections (BSIs) among intestinal and multivisceral transplant recipients in the 2-year post-operative period. METHODS: A retrospective medical record review of adult intestinal or multivisceral transplant recipients between 2003 and 2015. Descriptive statistics were used to describe cohort data. Logistic regression was used to assess factors related to BSIs using a backward selection process. RESULTS: One-hundred and six intestinal or multivisceral transplants were performed in 103 individuals. Fifty-eight percent (n = 62) developed a BSI in the 2-year post-operative period with a median time to first BSI of 53 days (interquartile range [IQR] 15, 169). The majority of BSIs were catheter related 38% (n = 58) when the source was known. Common microbiological isolates included enterococcus 20% (n = 36/174), coagulase-negative staphylococcus 14% (n = 23), and 12% Klebsiella spp (n = 21). Forty-seven percent (n = 17) of the enterococci were resistant to vancomycin, and 14% (n = 10/70) of the gram negatives were extended spectrum beta-lactamase (ESBL) producers. In adjusted analyses, (OR: 0.200 95% CI: 0.2, 0.514, P = .009) men were less likely to have a BSI. Transplant recipient age, allograft type, comorbidities, rejection, and length of stay were not noted to be risk factors for development of BSIs in our cohort. Mortality at 2-years post-transplant was similar for those who did not develop a BSI and those that developed infection, P = .5028. CONCLUSIONS: BSIs are a common complication of intestinal transplantation, and central venous catheters were a common source. Interventions such as early catheter removal should be implemented to prevent infections in this population. Female sex association with BSI requires further investigation.

Anti-plasma cell treatment in refractory autoimmune hemolytic anemia in a child with multivisceral transplant.

BACKGROUND: Warm-antibody AIHA is known to complicate solid organ (SOT) and HSCT, the disease maybe refractory to standard therapy. Immunosuppressive therapies as well as IVIG, and rituximab have been the main stay of treatment. Over the past decade, B-lymphocyte targeted, anti-CD-20 antibody has been recognized in the treatment of autoimmune diseases and utilized in AIHA. Bortezomib, a proteasome inhibitor that causes apoptosis of plasma cells, is an appealing targeted therapy in secondary AIHA and has demonstrated efficacy in HSCT patients. From our experience, we advocate for early targeted therapy that combines B cell with plasma cell depletion. CASE REPORT: We describe a 4-year-old-girl with stage III neuroblastoma, complicated with intestinal necrosis needing multivisceral transplant developed warm AIHA 1-year after transplantation, and following an adenovirus infection. She received immunoglobulin therapy, rituximab, sirolimus, plasmapheresis, and long-term prednisolone with no sustained benefit while developing spinal fractures related to the latter therapy. She received bortezomib for intractable AIHA in combination with rituximab with no appreciable adverse effects. Three years later the child remains in remission with normal reticulocyte and recovered B cells. In the interim, she required chelation therapy for iron overload related to blood transfusion requirement during the treatment of AIHA. CONCLUSION: We propose early targeted anti-plasma cell therapy with steroid burst, IVIG, rituximab, and possible plasmapheresis may reduce morbidity in secondary refractory w-AIHA.

Rhizomucor hepatosplenic abscesses in a patient with renal and pancreatic transplantation.

Fungal infections are generally observed in immunosuppressed patients only, with a diagnostic challenge due to non-specific symptoms. For this reason, appropriate management may be delayed. This case report concerns a 36-year-old man with history of pancreas and kidney transplantation. He had chemotherapy for post-transplant B-cell lymphoma and presented with left upper abdominal pain and fever. Multiple investigations led to a final diagnosis of disseminated abdominal mucormycosis with multiple Rhizomucor abscesses in the liver, spleen and kidney transplant. Treatment was antifungal therapy and laparotomy with splenectomy, wedge resection of two fungal abscesses in segments II and IVb, and segmental left colic resection.

Endovascular management of complete disruption of aortic anastomosis after pediatric multivisceral transplant.

Multivisceral transplantation is a life-saving treatment for many chronically ill patients with advanced abdominal pathologies. For such transplants, a complex arterial reconstruction is required, with numerous anastomoses on a composite donor graft and the native aorta. In these patients, anastomotic disruption or pseudoaneurysm formation, often in the setting of infection, are deadly complications. Open surgical repair is hazardous, because many of these patients have dense adhesions. Reported cases of disruption at the aortic anastomosis to date have resulted in patient demise. We report the case of a pediatric multivisceral transplant recipient with ruptured aortic pseudoaneurysm. He underwent an emergent endovascular parallel stent grafting technique, which successfully controlled bleeding and maintained graft perfusion.

Intra-abdominal infections among adult intestinal and multivisceral transplant recipients in the 2-year post-operative period.

BACKGROUND: Intestinal and multivisceral transplantations are treatment options for patients with intestinal failure. Transplantation is often complicated by abdominal and/or bloodstream infections in the post-operative period. METHODS: A retrospective chart review of all adults who underwent intestinal or multivisceral transplantation at our institution from 2003 to 2015 was performed. Data were collected for 2 years post transplant. RESULTS: A total of 106 intestinal or multivisceral transplants were performed in 103 patients. The median age at the time of transplant was 44 (IQR: 34-52) with 55% (n = 58) male and 45% (n = 48) female. There were 46 (43%) intra-abdominal infections post transplant among the 103 patients, and six transplant recipients (13%) developed concurrent bloodstream infections. The median time to first intra-abdominal infection was 23 days (IQR: 10-48). For those with organisms isolated in culture, forty-seven percent of the isolates were gram negative, 39% gram positive, 7% anaerobes, and 7% yeast. The most common isolates were enterococci at 28%, E. coli at 14%, and Klebsiella spp at 13%. Sixty-three percent of the enterococci were vancomycin-resistant enterococci (VRE), and 22% of the gram-negative isolates were extended spectrum beta-lactamases (ESBLs). Patients with intra-abdominal infections had longer hospital post-transplant length of stays at a median of 35 days (IQR: 25-48) vs 23 days (IQR: 17-33) for those without infections, P = .0012. There was no difference in all-cause mortality in patients with or without intra-abdominal infections, P = .654. CONCLUSIONS: Intra-abdominal infections are common in intestinal or multivisceral transplant recipients, but despite this complication, we found no increased risk of mortality. These transplant recipients are also at risk for infection with drug-resistant organisms.

Clostridium difficile infection mimics intestinal acute cellular rejection in pediatric multivisceral transplant-A case series.

Clostridium difficile infection (CDI) is the most common health care-associated infection in the United States. Thirty-nine percent of intestinal transplant recipients may develop CDI. Induction of rejection has been reported as a rare event. To our knowledge, this will be the second report of an association between CDI and rejection in the literature. We describe our experience with four pediatric MVT recipients, three of whom on treatment of their CDI alone had resolution of biopsy findings of intestinal ACR. Our patients were males aged 2-5 years old who had their first CDI post-MVT occurring from 2 months to 15 months post-transplant. All first episodes of CDI were treated with a 10-14 day course of metronidazole with one additionally receiving vancomycin. All four recipients had recurrent CDI, and two recipients had septic shock as a manifestation of their CDI. Three recipients had biopsies showing mild rejection during episodes of CDI, and treatment of the CDI resulted in resolution of biopsy findings of rejection. Our case series suggests CDI may mimic ACR on intestinal biopsy. Treatment of rejection during active CDI carries the risk of over-suppression and worsening of CDI. Our experience has taught us that surveillance endoscopy for rejection may be deceiving during an active CDI, and if mild acute rejection is noted during active CDI, treatment of rejection can be safely delayed and potentially avoided.

Fibrinolytic Shutdown Is Associated With Intraoperative Thrombosis and Hemorrhage During Visceral Transplant.

Background and Objective. End-stage liver disease is characterized by a precarious imbalance of hemostasis. Detrimental consequences of hypofibrinolysis, also known as fibrinolytic shutdown, have been recently demonstrated, and its significance in visceral (ie, an allograft that contains the intestine) transplant remains unknown. Design and Setting. To fill this gap, following institutional review board approval, this retrospective study included 49 adult recipients of visceral allografts (14 "visceral allograft without the liver" and 35 "multivisceral" with the liver) transplanted between 2010 and 2018 in a single university hospital, and for whom pre-incisional thromboelastography was available. Based on percent clot lysis 30 minutes after maximal amplitude, patients were stratified into 3 fibrinolysis phenotypes: fibrinolytic shutdown, physiologic fibrinolysis, and hyperfibrinolysis. Results. Fibrinolytic shutdown occurred in 57% of patients, with higher incidence in recipients of multivisceral transplant (69%) compared with visceral allograft without liver (29%) allografts (P = .04). Fibrinolytic shutdown was associated with an increase in both intraoperative thrombosis and hemorrhage. Intraoperative thrombosis (18%) occurred only with multivisceral transplant, and accounted for 36% of in-hospital mortality. A clinically meaningful reduction in incidence of intraoperative thrombosis was noted in recipients who received intravenous heparin thromboprophylaxis. Logistic regression identified pretransplant platelet count as a risk factor for fibrinolytic shutdown (odds ratio = 0.992, 95% confidence interval = [0.984-0.998]; χ2 = 7.8, P = .005). Conclusions. This study highlights fibrinolytic shutdown as a dominant and clinically important feature of the hemostatic imbalance in recipients undergoing visceral transplantation.

Post-intestine transplant graft-vs-host disease associated with inclusion of a liver graft and with a high mortality risk.

INTRODUCTION: This study reports the incidence, anatomic location, and outcomes of graft-vs-host disease (GVHD) at a single active intestine transplant center. METHODS: Records were reviewed for all patients receiving an intestine transplant from 2003 to 2015. Pathology reports and pharmacy records were reviewed to establish the diagnosis, location, and therapeutic interventions for GVHD. RESULTS: A total of 236 intestine transplants were performed during the study period, with 37 patients (16%) developing GVHD. The median time to onset of disease was 83 days, with 89% of affected patients diagnosed in the first year post-transplant. Mortality for affected patients was 54% in the 1 year after GVHD diagnosis. Skin lesions were the most common manifestation of GVHD. Other sites of disease included lungs, bone marrow, oral mucosa, large intestine, and brain. The incidence of GVHD was 16% in adult patients, and slightly lower in pediatric recipients (13%). In adults, increasing graft volume (isolated vs multi-organ) and liver inclusion were associated with increasing risk of GVHD, though this was not seen in pediatric patients. CONCLUSION: Overall, 16% of intestine transplant recipients developed GVHD. GVHD is associated with high mortality, and disease in the lungs, brain, and bone marrow was universally fatal.

T2Candida® to guide antifungal and lengh of treatment of candidemia in a pediatric multivisceral transplant recipient.

A case of 1-year- old male multivisceral transplant recipient with candidemia diagnosed by the T2Candida® test is presented. Optimal management of the candidemia complemented the treatment of the global clinical episode. Duration of treatment might be established much more precisely with the T2Candida® test than with blood cultures.

Thrombotic and hemorrhagic complications during visceral transplantation: risk factors, and association with intraoperative disseminated intravascular coagulation-like thromboelastographic qualities: a single-center retrospective study.

This study describes the risk of thrombotic and hemorrhagic complications, both intraoperatively, and up to 1 month following visceral transplantation. Data from 48 adult visceral transplants performed between 2010 and 2017 were retrospectively studied [32 multivisceral (MVTx); 10 isolated intestine; six modified-MVTx]. Intraoperatively, intracardiac thrombosis (ICT)/pulmonary embolism (PE) occurred in 25%, 0% and 0% of MVTx, isolated intestine and modified MVTx, respectively, and was associated with 50% (4/8) mortality. Preoperative portal vein thrombosis (PVT) was a significant risk factor for ICT/PE (P = 0.0073). Thromboelastography resembling disseminated intravascular coagulation (DIC) (r time <4 mm combined with fibrinolysis or flat-line) was statistically associated with occurrence of ICT/PE (P < 0.0001). Compared to subgroup without ICT/PE, occurrence of ICT/PE was associated with an increased demand for all blood product components both overall, and each surgical stage. Hyperfibrinolysis (56%) was identified as cause of bleeding in MVTx. Incidence of postoperative thrombotic event at 1 month was 25%, 30% and 17% for MVTx, isolated intestine and modified MVTx, respectively. Incidence of postoperative bleeding complications at 1 month was 11%, 20% and 17% for MVTx, isolated intestine and modified MVTx. In conclusion, MVTx recipients with preoperative PVT are at an increased risk of developing intraoperative life-threatening ICT/PE events associated with DIC-like coagulopathy.

Posttransplant complications in adult recipients of intestine grafts without bowel decontamination.

BACKGROUND: Selective digestive decontamination is commonly used to decrease lumenal bacterial flora. Preoperative bowel decontamination may be associated with a lower wound infection rate but has not been shown to decrease risk of intra-abdominal abscess or lower leak rate for enteric anastomoses. Alternatively, the decontamination disrupts the normal flora of the gastrointestinal tract and may affect normal physiology, including immunologic function. This study reports complication rates of an intestine transplant program that has never used bowel decontamination. METHODS: All adult patients who underwent intestine transplant from 2003 to 2015 at a single center were reviewed. Posttransplant complications included intra-abdominal abscess, enteric fistula, and leak from the enteric anastomosis. Viral, fungal, and bacterial infections in the first year after transplant are reported. RESULTS: There were 184 adult patients who underwent deceased donor intestine transplant during the study period. Among these patients, 30% developed an infected postoperative fluid collection, 4 developed an enteric fistula (2%), and 16 had an enteric or anastomotic leak (8%). The rate of any bacterial infection was 91% in the first year, with a wound infection rate of 25%. Fungal infection occurred in 47% of patients. Rejection rates were 55% at 1 y for isolated intestine patients and 17% for multivisceral (liver inclusive) patients. CONCLUSIONS: Among this population of intestine transplant patients in which no bowel decontamination was used, rates of surgical complications, infections, and rejection were similar to those reported by other centers. Bowel decontamination provides no identifiable benefit in intestine transplantation.

Graft versus host disease after multivisceral transplantation: A UK center experience and update on management.

Graft versus host disease (GVHD) following transplantation of an intestine-containing graft occurs more frequently than with other solid organ transplants and is known to have a poor outcome. The presentation differs from other solid organ transplants, as the gastrointestinal tract is not involved following intestinal transplant. Diagnosis is based on clinical symptoms arising due to native tissue damage and the detection of donor T lymphocytes in circulating blood (T-cell chimerism). The ideal treatment strategy has not been defined, with advocates for both increased and decreased immunosuppression. We reviewed all cases of GVHD in an adult intestinal transplant center in the United Kingdom and report on management strategies of five cases and methods of detecting T-cell chimerism. The practice in our center has evolved with experience. The first two patients received an increase in immunosuppression, which was only successful in one case. Subsequently, reducing immunosuppression has been more effective. However, patients with bone marrow involvement have a poorer prognosis. We demonstrate successful treatment of GVHD after multivisceral transplant with a reduction in immunosuppression. This should be followed by vigilant graft surveillance and serial monitoring of the level of T-cell chimerism, with reintroduction of immunosuppression at the earliest sign of graft dysfunction.

Complications in pediatric intestine transplantation in the absence of peri-operative donor or recipient bowel decontamination.

This study reports the clinical complication and infection rates of an active pediatric IT program that has never utilized bowel decontamination in either the donor or the recipient. All patients undergoing IT from 2003 to 2015 at a single pediatric IT center were reviewed. Post-transplant surgical, infectious, and immunosuppressive complications are reported. There were 52 patients who underwent IT during the study period. Among these patients, 4% developed a postoperative abscess, one developed an enteric fistula (2%), and one had an enteric or anastomotic leak (2%). The rate of any bacterial infection was 90% in the first year, with a wound infection rate of 23%. Any fungal infection occurred in 25% of patients. Any viral infection occurred in 75% of patients. Gastrointestinal viruses were diagnosed in 52% of patients, and cytomegalovirus infections occurred in 17%. Rejection rates were 39% at any time post-transplant (isolated 44% and 35% for multivisceral patients). At this center in which no bowel decontamination was used, rates of surgical complications, infections, and rejection were similar to those reported by other centers. These findings suggest bowel decontamination may provide no significant benefit in this population of high-risk transplant patients.

Pediatric patient with end-stage kidney disease secondary to Eagle-Barrett syndrome and metastatic unresectable hepatoblastoma treated successfully with chemotherapy and liver-kidney transplant.

HBL is the most common malignant liver neoplasm in children. The etiology of HBL is largely unknown but there are certain syndromes, such as Beckwith-Wiedemann syndrome, that have been clearly associated with an increased incidence of this malignancy. EBS, also known as prune belly syndrome, is a congenital anomaly characterized by lax abdominal musculature, bilateral cryptorchidism requiring, in some cases, hemodialysis due to significant kidney and urinary tract dysfunctions. Despite an improvement on the survival rates of patients with advanced-stage HBL, the presence of concomitant end-stage renal disease that occurs in patients with EBS constitutes a therapeutic challenge for the clinician not only due to the use of nephrotoxic chemotherapy but also due to the potential need for multi-organ transplant. We report case of a 2-year-old male patient with EBS diagnosed with stage IV, metastatic HBL successfully treated with multi-agent chemotherapy while on dialysis whom then underwent a simultaneous liver-kidney transplant followed by adjuvant chemotherapy. Ultimately, the patient achieved cancer remission with normalization of his renal function. Our report emphasizes that patients with HBL in the setting of EBS will not only require careful kidney function monitoring while receiving chemotherapy, but they might also need to undergo multi-organ transplantation in order to achieve adequate cancer control and also normalization of their kidney function. Awareness of this unusual association calls for further investigation to potentially establish a genetic association between these two disease processes.