Multivisceral Organ Transplant Research Articles

A case of delayed primary-CNS post-transplant lymphoproliferative disorder in a patient with concurrent metastatic colorectal malignancy

Introduction: Post-transplant lymphoproliferative disorders (PTLD) are a complication of immunosuppression following organ transplantation. Due to their heterogeneous presentation, diagnosis of PTLD can be challenging. Case Report: In this case report, we present a patient with metastatic colon cancer, with remote history of multivisceral organ transplant 20-years prior, who presented with altered mental status and was diagnosed with primary central nervous system PTLD. Conclusion: This case illustrates the importance of continued suspicion of PTLD long after transplantation in solid-organ transplant recipients, even in the setting of multiple comorbidities.

Multivisceral Transplant, The Prince Charles Hospital Experience

Multi-visceral organ transplant is uncommon. As a result of the rarity of these surgeries, there are limited studies, making it difficult to interpret outcomes and identify specific patient complications. We aim to assess the indications for multi-organ transplant, the time on the wait-list and evaluate outcomes including patient survival, graft survival and postoperative complications in an Australian context. Patients undergoing multi-organ transplant from 1993 to 2018 at The Prince Charles Hospital, Brisbane, Australia were retrospectively reviewed, looking at baseline characteristics and post-transplant morbidity, mortality and graft survival. A total of 37 patients were included in the study, comprising 22 heart-lung transplants, eight heart-kidney transplants and seven heart-lung-liver transplants. There were six domino heart transplants performed, all in the heart-lung-liver transplant group. The mean age at transplant was 37 years and the mean wait-list time was 10 months. One patient, receiving a heart-lung transplant, required re-transplantation (bilateral lung) at 3 years. One-year (1-year) survival was 91% for heart-lung transplants, 86% for heart-lung-liver transplants and 87.5% for heart-kidney transplants. Five- and ten-year (5- and 10-year) survival was 79% for both in heart-lung transplant, 43% and 29% for heart-lung-liver transplant and 87.5% for both in heart-kidney transplant. Patients undergoing multi-organ transplant at our unit had long-term survival and organ function comparable to international data. In addition, waitlist time for multi-organ transplant was not found to be excessive.

Underimmunization of the solid organ transplant population: An urgent problem with potential digital health solutions.

Solid organ transplant recipients are at risk for potentially life-threatening infections due to lifelong immunosuppression. Vaccine-preventable infections result in graft injury, morbidity, mortality, and significantly increased medical costs. Unfortunately, the majority of transplant recipients continue to be underimmunized at the time of transplant and thereafter. Given the rising rates of vaccine hesitancy and refusal in the general population, transplant recipients can no longer rely on herd immunity to protect them from vaccine-preventable infections. Novel tools are desperately needed to overcome transplant-specific immunization barriers to improve immunization rates in this high-risk population. Digital health technologies may offer a solution by addressing transplant-specific barriers: specifically, providing accurate information about vaccine safety, efficacy, and timing in the pre- and posttransplant periods; making a complete immunization record universally available and easily accessible; enabling communication between patients and multiple providers; and providing automated vaccine reminders to both patients and providers when vaccines are due using transplant-specific immunization guidelines. Digital health has transformed health care by empowering patients with their own health information and connecting patients, their providers, and public health officials. In doing so, it offers a potential platform to address and overcome the problem of underimmunization in the transplant population.

Multivisceral Transplant: The Prince Charles Experience

Purpose: Multivisceral organ transplant is uncommon, with a number of indications. As a result of the rarity of these surgeries, there are limited reports, which make it difficult to interpret outcomes and identify specific complications for these patients. This study aimed to assess the indications for multi-organ transplant and evaluate outcomes, including waiting list time, patient survival, graft survival, and postoperative complications in an Australian context.

Epidemiology and outcomes of pretransplant methicillin-resistant StaphylococcusAureus screening in pediatric solid organ transplant candidates.

MRSA infection following SOT is an important cause of morbidity and mortality, but epidemiology and risk factors for colonization prior to pediatric SOT remain unclear. A retrospective cohort of SOT patients ≤21years of age from 2009 to 2014 was evaluated. Demographics, MRSA screens, timing of transplantation, and MRSA infection were abstracted. From 2013 to 2014, 130 SOT candidates were screened or had known prior MRSA infection. Seventeen patients (13%) were MRSA colonized. Liver transplant candidates were least likely to be colonized (OR 0.22, CI:0.06-0.81, P=.02); greatest risk of colonization was in lung (OR 18.7, CI:1.9-182.3, P=.03), abdominal multivisceral (OR 7.5, CI:1.5-38.6, P=.02), and cardiac patients with history of cardiothoracic surgery (OR 8.0, CI:1.7-36.0, P=.007). In univariable analysis, African American patients were more likely to be colonized (OR 7.1, CI:2.49-19.41, P=.0005). There were 3 early MRSA infections in screened patients, incidence of 3.9%; only one in a colonized patient. Thirteen percent of screened pediatric SOT candidates were MRSA colonized, with greatest risk in lung, multivisceral and cardiac patients with prior cardiothoracic surgery. Early MRSA infection occurred in 3.9% of transplanted patients. Cardiothoracic and multivisceral organ transplant candidates may benefit the most from targeted MRSA screening.

Hemophagocytic lymphohistiocytosis presenting in a pediatric patient with near total colonic and small bowel aganglionosis: a case report

BackgroundTotal colonic and small bowel aganglionosis is a rare condition typically requiring intestinal transplant for long-term survival. There have not been any previously reported cases of near total intestinal aganglionosis complicated by concerns for hemophagocytic lymphohistiocytosis and need for both multivisceral organ transplant and hematopoietic stem cell transplant.Case presentationOur patient is a 35-month-old Egyptian boy who presented with bilious emesis and failure to pass meconium shortly after birth. After evaluation, he was found to have near total colonic and small bowel aganglionosis up to the ligament of Treitz. When he was transferred to our tertiary facility, he was already diagnosed as having aganglionosis of total colon and partial small bowel whose case is complicated by the concern for hemophagocytic lymphohistiocytosis. He was not able to absorb any substantial nutrition enterally and was stabilized on long-term total parenteral nutrition which resulted in total parenteral nutrition-induced liver injury. While awaiting evaluation for liver and bowel transplant, he developed concerning symptoms consistent with hemophagocytic lymphohistiocytosis. He presents a complex challenge creating difficulty with management of whether to proceed with bowel transplant as a result of near-total intestinal aganglionosis or hematopoietic stem cell transplant for treatment of hemophagocytic lymphohistiocytosis. In this case, the transplant team proceeded with visceral transplant first, however he did not survive.ConclusionsThis presentation of aganglionosis of total colon and partial small bowel complicated by the concern for hemophagocytic lymphohistiocytosis is unique to medical literature. For many physicians involved it is hard to determine how best to proceed with next steps in care.

Transmission of Hepatitis A Virus through Combined Liver-Small Intestine-Pancreas Transplantation.

Although transmission of hepatitis A virus (HAV) through blood transfusion has been documented, transmission through organ transplantation has not been reported. In August 2015, state health officials in Texas, USA, were notified of 2 home health nurses with HAV infection whose only common exposure was a child who had undergone multi-visceral organ transplantation 9 months earlier. Specimens from the nurses, organ donor, and all organ recipients were tested and medical records reviewed to determine a possible infection source. Identical HAV RNA sequences were detected from the serum of both nurses and the organ donor, as well as from the multi-visceral organ recipient's serum and feces; this recipient's posttransplant liver and intestine biopsy specimens also had detectable virus. The other organ recipients tested negative for HAV RNA. Vaccination of the donor might have prevented infection in the recipient and subsequent transmission to the healthcare workers.

Prolonged post-reperfusion syndrome during multivisceral organ transplantation in a pediatric patient: a case report.

Multivisceral organ transplantation involves the transplantation of three or more abdominal organs, including small bowel, duodenum, stomach, liver, pancreas, colon, and so on. The large amounts of cold and acidic loading into systemic circulation from the graft during multivisceral organ transplantation may result in severe post-reperfusion syndrome (PRS). We describe here a 6-year-old pediatric patient with chronic intestinal pseudo-obstruction who experienced prolonged PRS and severe metabolic acidosis during seven abdominal organ transplantation including the liver, spleen, stomach, duodenum, small bowel, colon and pancreas. The hypotensive period lasted approximately 10 minutes after graft reperfusion and was accompanied by severe metabolic acidosis and hypothermia. Since PRS can be easily associated with adverse outcomes, such as poor early graft function and primary non-function, not only meticulous surveillance for aggravating factors for PRS but also their immediate correction were necessary in managing a pediatric patient undergoing multivisceral organ transplantation.

Fluorescence In Situ Hybridization (FISH) as an Aid for the Diagnosis of Graft-Versus-Host Disease in Two Multivisceral Organ Transplant Patients

We herein describe 2 cases of adult multivisceral transplant patients who developed graft-versus-host disease manifesting predominantly as lichenoid skin papules and plaques. The diagnosis was supported by histopathology but ultimately corroborated by the utilization of the fluorescence in situ hybridization (FISH) technique using X and Y chromosome probes on unstained biopsy slides. In both cases, FISH revealed a high percentage of donor-derived cells as part of the inflammatory infiltrate in the skin biopsy. This report adds to the previous publications showing the utility of FISH in corroborating the diagnosis of graft-versus-host disease in transplant patients with unmatched sex donor.

Tissue Engineering of the Intestine in a Murine Model

Tissue-engineered small intestine (TESI) has successfully been used to rescue Lewis rats after massive small bowel resection, resulting in return to preoperative weights within 40 days.1 In humans, massive small bowel resection can result in short bowel syndrome, a functional malabsorptive state that confers significant morbidity, mortality, and healthcare costs including parenteral nutrition dependence, liver failure and cirrhosis, and the need for multivisceral organ transplantation.2 In this paper, we describe and document our protocol for creating tissue-engineered intestine in a mouse model with a multicellular organoid units-on-scaffold approach. Organoid units are multicellular aggregates derived from the intestine that contain both mucosal and mesenchymal elements,3 the relationship between which preserves the intestinal stem cell niche.4 In ongoing and future research, the transition of our technique into the mouse will allow for investigation of the processes involved during TESI formation by utilizing the transgenic tools available in this species.5The availability of immunocompromised mouse strains will also permit us to apply the technique to human intestinal tissue and optimize the formation of human TESI as a mouse xenograft before its transition into humans. Our method employs good manufacturing practice (GMP) reagents and materials that have already been approved for use in human patients, and therefore offers a significant advantage over approaches that rely upon decellularized animal tissues. The ultimate goal of this method is its translation to humans as a regenerative medicine therapeutic strategy for short bowel syndrome.

Tissue Engineering of the Intestine in a Murine Model

Tissue-engineered small intestine (TESI) has successfully been used to rescue Lewis rats after massive small bowel resection, resulting in return to preoperative weights within 40 days.(1) In humans, massive small bowel resection can result in short bowel syndrome, a functional malabsorptive state that confers significant morbidity, mortality, and healthcare costs including parenteral nutrition dependence, liver failure and cirrhosis, and the need for multivisceral organ transplantation.(2) In this paper, we describe and document our protocol for creating tissue-engineered intestine in a mouse model with a multicellular organoid units-on-scaffold approach. Organoid units are multicellular aggregates derived from the intestine that contain both mucosal and mesenchymal elements,(3) the relationship between which preserves the intestinal stem cell niche.(4) In ongoing and future research, the transition of our technique into the mouse will allow for investigation of the processes involved during TESI formation by utilizing the transgenic tools available in this species.(5)The availability of immunocompromised mouse strains will also permit us to apply the technique to human intestinal tissue and optimize the formation of human TESI as a mouse xenograft before its transition into humans. Our method employs good manufacturing practice (GMP) reagents and materials that have already been approved for use in human patients, and therefore offers a significant advantage over approaches that rely upon decellularized animal tissues. The ultimate goal of this method is its translation to humans as a regenerative medicine therapeutic strategy for short bowel syndrome.

Purpura Fulminans Associated with Streptococcus pneumoniae Septicemia in an Asplenic Pediatric Patient

Purpura fulminans is a rapidly progressive syndrome of small-vessel thrombosis and hemorrhagic necrosis of the skin accompanied by disseminated intravascular coagulation. We describe a case of Streptococcus pneumoniae septicemia in an asplenic 5-year-old boy on oral tacrolimus, with a past medical history of multivisceral organ transplantation and subsequent development of purpura fulminans on his chest and distal extremities. The acute infectious form of purpura fulminans is usually caused by gram-negative bacteria. Cases secondary to gram-positive encapsulated bacteria usually occur when individuals are immuno-suppressed or have anatomic or functional asplenia. Our patient had both, which likely increased his susceptibility, and he responded well to antimicrobial therapy in addition to prophylactic coverage in the setting of his immunosuppression. We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans.

Evaluation of the Masimo® Rainbow SET Radical-7 in a 6-month-old pediatric multivisceral organ transplant

Evaluation of the Masimo® Rainbow SET Radical-7 in a 6-month-old pediatric multivisceral organ transplant

Severe cold agglutinin disease caused by recurrent monomorphic Epstein–Barr virus (EBV)‐associated post‐transplant lymphoproliferative disorder (PTLD), clonally related to an EBV‐negative plasmacytic hyperplasia in a pediatric multivisceral organ transplant recipient

PTLD represent major post-transplant complications. The major etiologic factor is EBV. Association with cold agglutinin disease has not been described so far. We report a three-yr-old girl who developed oligoclonal EBV-negative plasmacytic hyperplasia as well as Coombs test-positive anemia one yr after multivisceral organ transplantation, performed after subtotal bowel resection for colointestinal aganglionosis and liver cirrhosis resulting from long-term parenteral nutrition. The patient was treated for plasmacytic hyperplasia with cyclophosphamide and prednisolone and achieved clinical remission. One yr later PTLD progressed possibly driven by EBV to DLBCL. The migration patterns of the amplified Ig heavy chain genes demonstrated a probable clonal relationship of the DLBCL to a clone almost present in the plasmacytic hyperplasia. This progression was accompanied by a rapid rise of cold agglutinin titers with symptoms of severe cold agglutinin disease, leading to right femoral and extern iliac vein thromboses requiring partial leg amputation. After four cycles of rituximab, cyclophosphamide, and prednisolone, the patient achieved complete PTLD remission and the cold agglutinins disappeared. Summarizing, PTLD may be accompanied by cold agglutinin disease, and both may be successfully treated by immuno-chemotherapy. The appearance of cold agglutinins in transplant patients may indicate PTLD development.

Cutaneous Zygomycosis Associated With Urate Panniculitis

Cutaneous zygomycosis is being increasingly recognized as a serious and life-threatening infection in debilitated and immunosuppressed patients, including transplant patients. The organisms are morphologically distinct but difficult to grow in cultures from clinical samples. We report a case of cutaneous zygomycosis in a neonatal multi-visceral organ transplant patient, with subcutaneous panniculitis accompanied by extensive local acicular uric acid crystal deposition. Although the patient's serum uric acid was subsequently found to be in the normal range, transient hyperuricemia could not be excluded. Because we use a microwave-based processing system avoiding aqueous solutions, the crystals were maintained in the tissue sections and were shown by various methods to consist of monosodium urate. Early diagnosis combined with extensive debridement and prompt antifungal therapy resulted in a successful outcome. We have coined the term "urate panniculitis" to describe this phenomenon.

Outcome, Incidence, and Timing of Infectious Complications in Small Bowel and Multivisceral Organ Transplantation Patients

Infectious complications still represent a major cause of morbidity and mortality in patients with organ transplantation. In particular, small bowel or multivisceral transplantation is complicated to a greater extent than other grafts as a consequence of infectious complications including sepsis. This prospective study assessed outcome, incidence, and timing of infections in sequential patients undergoing small bowel or multivisceral transplantation (SB/MVTx) performed at a university transplant center between January 2001 and October 2003. Nineteen patients underwent transplantation during this period, 13 of whom (68%) undergoing isolated SB and 6 (32%) MV grafts with or without liver. The median follow up was 524 days (interquartile range=252-730) with an overall 24.4 person/year of observation. Postoperative mortality rate was 0.1 death/person/year; all patients, except one who died intraoperatively, were alive 6 months postsurgery. There were 100 documented infections including: 59 bacterial (2.4 events/person/year), 35 viral (1.4 events/person/year) and 6 fungal (0.2 events/person/year). Patients developed at least one episode of bacterial infection in 94% of the cases, viral infection in 67%, and fungal infection in 28%. This cohort describes the very common and complex nature of infectious complications in this challenging group of transplantation patients. Larger cohorts are needed to specifically address infection risk factors and longer term outcomes.

What Clinicians Can Learn from Life with Fred

I am a dietitian working in home nutrition support. I know a lot about it because I can assess a patient’s nutritional status and monitor their progress on home enteral or parenteral nutrition. I even know that long-term patients prefer to be called consumers because they aren’t “patients” anymore—home nutrition support is a way of life. That of course is what I thought until I got to know the consumers. Truthfully, I didn’t know about home nutrition support, not really. Technically, yes—but living the life—no. Robbyn Kindle’s article entitled “Life with Fred” details her experiences not only with home parenteral nutrition (HPN) but also with multivisceral organ transplant. Robbyn and other consumers have taught me about the reality of home nutrition support. I cannot remember all of the names nor the nutrition support regimens over time but I can remember the stories and the homes. I remember the retired couple, the husband receiving home enteral nutrition, who were one of my first to visit at home. I provided the information to a family—not just a patient. One gentleman on HPN I met with told me how to refinish a piece of furniture as he had done in his home—that was what he was proud of. My friend Bill, a 26-year veteran of HPN, provides me with the history of HPN because he has been receiving it that long. It is essential that nutrition support practitioners who work with home nutrition support consumers try to understand the challenges of living with home nutrition support. Do you know what it is like to store supplies for enteral or parenteral nutrition at your home? Did you as a clinician figure out a tube feeding formula that is easy to prepare or did you mix two different formulas together along with a modular product? Could you do that at home? Will it be paid for by your consumer’s insurance company? Do the HPN infusion hours meet your consumer’s needs, or could they be changed and improve their quality of life? That is why Robbyn’s article—her story really— is so important. It is the truth about HPN. HPN has been her lifeline as it is for many long-term consumers—that doesn’t mean she has to like it all of the time or that she has to infuse because you the clinician tells her she has to. She and others like her make a conscious decision, every day, to take in nutrition. We are a team—the consumer and the nutrition support practitioner. By working together, we can learn from one another. Ask questions of the consumer, even hard questions. Robbyn says to listen, take time, and understand the reality of home nutrition support. This will benefit us all. Thanks, Robbyn, for sharing your story. Correspondence: Carol Ireton-Jones, PhD, RD, LD, CNSD, Coram Healthcare, 1730 Countryside Drive, Carrollton, TX 75007. Electronic mail may be sent to drcijrd@attglobal.net.