|
1
|
Dumronggittigule W, Kositamongkol P, Sirivatanauksorn Y, Limsrichamrern S, Mahawithitwong P, Tovikkai C, Sangserestid P, Assawasirisin C. Multivisceral transplantation as a rescue treatment for intestinal failure following pancreaticoduodenectomy: A case report. World J Transplant 2025; 15:101427. [DOI: 10.5500/wjt.v15.i3.101427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 01/29/2025] [Accepted: 03/17/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Post-pancreaticoduodenectomy (PD) intestinal failure (IF) is rare and associated with poor outcomes. To our knowledge, the role of intestinal transplantation (ITx) as a rescue treatment for this complication has never been reported.
CASE SUMMARY A 42-year-old female with a benign neurilemmoma of the duodenum underwent PD. Her superior mesenteric vein (SMV) was injured during surgery and required reconstruction. She experienced SMV thrombosis and bowel gangrene requiring massive bowel resection. Consequently, she developed short gut syndrome and an enterocutaneous fistula, leading to prolonged hospitalization for wound care and total parenteral nutrition (TPN) support. She was referred to our hospital for ITx evaluation. Upon arrival, she had cholestasis due to IF-associated liver disease. After gastrointestinal (GI) reconstruction to restore GI continuity, she was eligible for multi-visceral transplantation (MVTx). The anticipated allograft included the stomach, small intestine, liver, pancreas, and duodenum. She found a suitable donor after two years of waiting. The MVTx procedure was straightforward with signs of immediate function. Enteral feeding was initiated on postoperative day (POD) 7. TPN weaning was achieved on POD 28, and the patient was discharged on POD 69. Two years post-MVTx, she is healthy with excellent graft function. To our knowledge, this is the first case report on MVTx as the treatment for fatal post-PD complications and also the first reported case of ITx in Southeast Asia.
CONCLUSION Post-PD IF is rare and lethal. Intestinal and MVTx might be a rescue treatment for IF after GI surgery in eligible patients.
Collapse
Affiliation(s)
| | - Prawat Kositamongkol
- Department of Surgery, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand
| | | | | | - Prawej Mahawithitwong
- Department of Surgery, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand
| | - Chutwichai Tovikkai
- Department of Surgery, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand
| | | | | |
Collapse
|
|
2
|
Boteon YL, Rocha MHMD, Haddad L, Pecora RAA, Lee ADW, Santos CY, Boteon APCDS, Calil I, Rossi GG, Marques F, Facas B, D'Albuquerque LAC. A multicentric observational retrospective study on patients with short bowel syndrome and chronic intestinal failure who underwent intestinal transplantation in Brazil. Clinics (Sao Paulo) 2024; 79:100521. [PMID: 39461196 PMCID: PMC11541937 DOI: 10.1016/j.clinsp.2024.100521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 08/08/2024] [Accepted: 09/20/2024] [Indexed: 10/29/2024] Open
Abstract
INTRODUCTION Short Bowel Syndrome (SBS) is a rare gastrointestinal disorder associated with Intestinal Failure (SBS-IF) that leads to morbidity, mortality, and a burden on healthcare costs. Intestine Transplantation (IT) is a treatment option for patients with SBS-IF as it replaces the missing or diseased intestine and offers the potential for return to normal activities and intestinal function. This study aims to describe the clinical course and demographical and clinical characteristics of subjects with SBS-IF who underwent IT in Brazil. METHODS This retrospective observational study included all SBS-IF patients who underwent IT in two reference centers in Brazil from April 2011 to December 2021. RESULTS A total of 7 young male participants were included in the study. The most frequent underlying condition was surgical complications, followed by intestinal volvulus and incisional hernia. The most frequent indication for IT was a hepatic disease associated with total Parenteral Nutrition (PN). The main type of IT performed was intestine only. The median time from underlying condition to IT was 67.3 (16.5‒88.5) months. The mean (SD) number of yearly hospitalizations per patient was 0.5 (0.3). The most common reason for hospitalization was PN-related complications. Sixty exams were performed in-hospital and 53 in the outpatient setting. CONCLUSION The findings of this study may be helpful to understand better the journey of patients with SBS-IF to IT in Brazil, providing real-world evidence to develop health policy guidelines and improve the quality of life of these patients.
Collapse
Affiliation(s)
| | | | - Luciana Haddad
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
| | | | - Andre Dong Won Lee
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | | | | | - Igor Calil
- Hospital Israelita Allbert Einstein, São Paulo, SP, Brazil
| | - Giovana Garcia Rossi
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | | | - Bianca Facas
- Takeda Distribuidora Ltda, São Paulo, SP, Brazil
| | | |
Collapse
|
|
3
|
Smullin CP, Venick RS, Marcus EA, McDiarmid SV, Yersiz H, Busuttil RW, Farmer DG. Intestinal Re-Transplantation. Gastroenterol Clin North Am 2024; 53:453-459. [PMID: 39068006 DOI: 10.1016/j.gtc.2024.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
Abstract
The history of intestinal transplantation can be traced back to the turn of the twentieth century. Although advancements have been made, the intestine still presents a greater challenge to transplantation than does that of other solid organs, experiencing higher rates of graft rejection and lower long-term survival. Increasingly, intestinal re-transplantation (re-ITx) is seen as a viable option and is now the fourth most common indication for ITx. Changes to immunosuppression protocols, technical modifications, and infectious disease monitoring have contributed to improved outcomes. The authors review the literature on re-ITx in regard to the history, management considerations, and future directions.
Collapse
Affiliation(s)
- Carolyn P Smullin
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Robert S Venick
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Elizabeth A Marcus
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Suzanne V McDiarmid
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Hasan Yersiz
- Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont UCLA Transplant Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Ronald W Busuttil
- Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont UCLA Transplant Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Douglas G Farmer
- Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont UCLA Transplant Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
| |
Collapse
|
|
4
|
Garcia J, Vianna R. B-Cell Induction Therapies in Intestinal Transplantation. Gastroenterol Clin North Am 2024; 53:343-357. [PMID: 39067999 DOI: 10.1016/j.gtc.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
Abstract
Despite advancements in short-term outcomes since the inception of intestinal transplant, significant long-term graft failure persists. Early successes are attributed to the utilization of tacrolimus for maintenance therapy, coupled with T-cell modulating induction regimens, which effectively reduce the incidence of acute cellular rejection. However, the challenge of chronic allograft injury remains unresolved. There is increasing evidence indicating a correlation between donor-specific antibodies and the survival of visceral allografts. Strategies aimed at reducing the presence or load of these antibodies may potentially enhance long-term outcomes. Consequently, our focus is now turning toward B-cell induction therapies as a possible solution.
Collapse
Affiliation(s)
- Jennifer Garcia
- Adult and Pediatric Intestinal Transplant, Miami Transplant Institute, University of Miami-Jackson Memorial Hospital, 1801 Northwest 9th Avenue, MTI 7th Floor, Jackson Professional Building, Miami, FL 33136, USA.
| | - Rodrigo Vianna
- Adult and Pediatric Intestinal Transplant, Miami Transplant Institute, University of Miami-Jackson Memorial Hospital, 1801 Northwest 9th Avenue, MTI 7th Floor, Jackson Professional Building, Miami, FL 33136, USA
| |
Collapse
|
|
5
|
McArdle R, Cope R, Chaudhry A, Sharkey L, Peacock S. Exploring the immunological relevance of pre-transplant donor-specific antibody in intestinal transplantation, with special consideration to the liver. Int J Immunogenet 2024; 51:217-227. [PMID: 38637869 DOI: 10.1111/iji.12670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 02/19/2024] [Accepted: 03/15/2024] [Indexed: 04/20/2024]
Abstract
Despite recent advances that have improved outcomes following intestinal transplantation (ITx), achieving long-term patient survival and rejection-free survival is still challenging. Understanding the relevance of pre-transplant human leukocyte antigen (HLA) donor-specific antibody (DSA) in ITx and the immunomodulatory potential of the liver within the allograft is crucial to providing an accurate assessment of pre-transplant immunological risk, which could influence and improve post-transplant outcomes further. This was the primary objective of this retrospective study of 95 adult ITx transplants which took place at Cambridge University Hospitals (United Kingdom) between 2007 and 2019. Two novel programs were developed and validated to identify DSA (tested by Luminex single antigen beads) in this dataset. Data analysis utilised Kaplan-Meier survival methods, and statistical analysis was performed using log-rank tests and adjusted Cox models. Fifty-four (57%) ITx cases contained a liver, and 36 (38%) were sensitised to HLA. Pre-transplant DSA > 500 mean fluorescent intensity appeared to negatively affect post-ITx patient survival and rejection outcomes. Additionally, liver-inclusive allografts seemed to show particular resistance to HLA class I DSA. Our data hints towards consistency with other ITx studies where deleterious effects of DSA have been demonstrated, and where liver inclusion is protective from HLA class I DSA. This is in line with current national guidelines for immunological risk. Our publicly available research programs could support future large or multicentre studies where statistically relevant data might be gained.
Collapse
Affiliation(s)
- Rhea McArdle
- Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK
- Faculty of Biology, Medicine and Health, Division of Medical Education, School of Medical Sciences, University of Manchester, Manchester, UK
- Transplant Laboratory, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Gwendolen Road, Leicester, UK
| | - Rebecca Cope
- Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK
- Faculty of Biology, Medicine and Health, Division of Medical Education, School of Medical Sciences, University of Manchester, Manchester, UK
| | - Afzal Chaudhry
- Department of Nephrology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK
- Department of Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge, UK
| | - Lisa Sharkey
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK
| | - Sarah Peacock
- Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK
| |
Collapse
|
|
6
|
Trentadue G, Mensink PBF, Kruse C, Reszel B, Kats-Ugurlu G, Blokzijl T, Haveman JW, Faber KN, Dijkstra G, Hölscher UM, Kolkman JJ, Knichwitz G. Intraluminal oxygen can keep small bowel mucosa intact in a segmental ischemia model. Sci Rep 2024; 14:13732. [PMID: 38877069 PMCID: PMC11178904 DOI: 10.1038/s41598-024-64660-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 06/11/2024] [Indexed: 06/16/2024] Open
Abstract
Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Macro- and microscopically, the luminal oxygen delivered treatment group showed preserved small bowel's appearance, viability, and mucosal integrity. A gradual deterioration of histopathology and barrier markers and increase in hypoxia-inducible factor 1-α expression towards the sites most distant from the oxygen application was observed. Intraluminal low-flow, high oxygen delivery can preserve the intestinal mucosa during total ischemia of the small intestine. This finding can be incorporated in methods to overcome small bowel ischemia and improve intestinal preservation for transplantation.
Collapse
Affiliation(s)
- Guido Trentadue
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands.
| | - Peter B F Mensink
- Department of Internal Medicine and Gastroenterology, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Claudius Kruse
- Department of Anaesthesiology, University Hospital Muenster, Muenster, Germany
- Department of Anaesthesiology and Operative Intensive Medicine, Franziskus Hospital, Intensive Care Medicine, Bielefeld, Germany
| | - Bernward Reszel
- CERES GmbH, Clinical Evaluation and Research, Lörrach, Germany
- Berufliche Fortbildungszentren der Bayerischen Wirtschaft (bfz) gGmbH, München, Germany
| | - Gursah Kats-Ugurlu
- Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Tjasso Blokzijl
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jan Willem Haveman
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Klaas Nico Faber
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands
| | - Uvo M Hölscher
- Münster University of Applied Sciences, Steinfurt, Germany
| | - Jeroen J Kolkman
- Department of Internal Medicine and Gastroenterology, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Gisbert Knichwitz
- Department of Anaesthesiology, University Hospital Muenster, Muenster, Germany
- Dreifaltigkeits-Krankenhaus Cologne, Klinik Für Anästhesiologie, Intensivmedizin Und Schmerztherapie, Cologne, Germany
| |
Collapse
|
|
7
|
Matsumoto R, Kato T. Intestinal Transplantation: Include the Spleen with Intestinal Graft? Gastroenterol Clin North Am 2024; 53:281-288. [PMID: 38719378 DOI: 10.1016/j.gtc.2023.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
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.
Collapse
Affiliation(s)
- Rei Matsumoto
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center
| | - Tomoaki Kato
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center.
| |
Collapse
|
|
8
|
Xu Q, Zeevi A, Ganoza A, Cruz RJ, Mazariegos GV. Current approaches for risk assessment of intestinal transplant patients: A view from the histocompatibility laboratory. Hum Immunol 2024; 85:110768. [PMID: 38433035 DOI: 10.1016/j.humimm.2024.110768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/12/2024] [Accepted: 02/21/2024] [Indexed: 03/05/2024]
Abstract
Despite its recent decline in volumes, intestinal transplantation remains an important option for patients with irreversible intestinal failures. The long-term outcome of an intestinal transplant has stagnated. The major cause of graft loss is rejection, resulting from mismatches in human leukocyte antigens (HLA) and the presence of antibodies to mismatched donor-specific HLA antigens (DSA). Literature has reported that DSAs, either preformed before transplantation or developed de novo after transplantation, are harmful to intestinal grafts, especially for those without combined liver grafts. A comprehensive assessment of DSA by the histocompatibility laboratory is critical for successful intestinal transplantation and its long-term survival. This paper briefly reviews the history and current status of different methods for detecting DSA and their clinical applications in intestinal transplantation. The focus is on applying different antibody assays to manage immunologically challenging intestinal transplant patients before and after transplantation. A clinical case is presented to illustrate the complexity of HLA tests and the necessity of multiple assays. The review of risk assessment by the histocompatibility laboratory also highlights the need for close interaction between the laboratory and the intestinal transplant program.
Collapse
Affiliation(s)
- Qingyong Xu
- Department of Pathology, University of Pittsburgh, USA.
| | - Adriana Zeevi
- Department of Pathology, University of Pittsburgh, USA
| | | | - Ruy J Cruz
- Department of Surgery, University of Pittsburgh, USA; Gastrointestinal Rehabilitation and Transplant Center, Starzl Transplantation Institute, USA
| | - George V Mazariegos
- Department of Surgery, University of Pittsburgh, USA; Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh, USA
| |
Collapse
|
|
9
|
Klein K, Keck M, Langewisch E, Merani S, Hitchman K, Leick M. Evaluation of serial monitoring of donor-specific antibodies in pediatric and adult intestinal/multivisceral transplant recipients. Pediatr Transplant 2024; 28:e14638. [PMID: 37942670 DOI: 10.1111/petr.14638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/23/2023] [Accepted: 10/24/2023] [Indexed: 11/10/2023]
Abstract
BACKGROUND The study purpose was to add to limited literature assessing anti-HLA donor-specific antibody (DSA) appearance, clearance, specificity, and impact in intestinal/multivisceral (MV) transplant as well as the value of serial monitoring following an institutional protocol shift implementing serial monitoring. METHODS This single-center retrospective review included intestinal/MV recipients transplanted 1/1/15-9/31/17 with completed DSA testing. Patients were divided into groups based on DSA presence post-transplant. The primary outcome was biopsy-proven acute rejection (BPAR). Secondary outcomes included graft loss and death. Descriptive analysis of DSA was completed. RESULTS Of the 35 intestinal/MV recipients (60% pediatric) with DSA testing, 24 patients had post-transplant DSA. Fifteen patients in the DSA(+) group had T-cell-mediated BPAR versus five in the DSA(-) group (63% vs 45%, p = .47). Days to BPAR were 25 [IQR 19-165] (DSA(+) group) versus 232 [IQR 25.5-632.5] (DSA(-) group) (p = .066). There were no differences between groups for graft loss or death. One hundred and five DSA were identified in the DSA(+) group with 63% being class II, and 54% cleared during follow-up. DSA were directed against 50 different HLA alleles, with the most common being directed against HLA- DQ (35%). Time to first DSA and to clearance did not differ between class I and II. CONCLUSION Findings confirm previous data that suggest post-transplant DSA in this population may lead to increased BPAR or shorter time to BPAR, although not statistically significant. Most DSA were identified within the first month after transplant, and ahead of rejection identification on biopsy. DSA therefore may have utility as an early rejection biomarker and use may be considered in place of early protocol biopsies, particularly in pediatric patients. We identified novel findings of DSA directed against a large breadth of HLA in intestinal/MV patients.
Collapse
Affiliation(s)
- Kelsey Klein
- University Health Transplant Institute, San Antonio, Texas, USA
- The University of Texas at Austin, College of Pharmacy, Pharmacotherapy Division, Austin TX, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Megan Keck
- Nebraska Medicine, Omaha, NE, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Eric Langewisch
- Nebraska Medicine, Omaha, NE, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Shaheed Merani
- Nebraska Medicine, Omaha, NE, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Kelley Hitchman
- University Health Transplant Institute, San Antonio, Texas, USA
- Department of Pathology and Laboratory Medicine, UT Health San Antonio, San Antonio, Texas, USA
| | - Mary Leick
- Nebraska Medicine, Omaha, NE, University of Nebraska Medical Center, Omaha, Nebraska, USA
| |
Collapse
|
|
10
|
Battle R, Pritchard D, Peacock S, Hastie C, Worthington J, Jordan S, McCaughlan JA, Barnardo M, Cope R, Collins C, Diaz-Burlinson N, Rosser C, Foster L, Kallon D, Shaw O, Briggs D, Turner D, Anand A, Akbarzad-Yousefi A, Sage D. BSHI and BTS UK guideline on the detection of alloantibodies in solid organ (and islet) transplantation. Int J Immunogenet 2023; 50 Suppl 2:3-63. [PMID: 37919251 DOI: 10.1111/iji.12641] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 10/04/2023] [Indexed: 11/04/2023]
Abstract
Solid organ transplantation represents the best (and in many cases only) treatment option for patients with end-stage organ failure. The effectiveness and functioning life of these transplants has improved each decade due to surgical and clinical advances, and accurate histocompatibility assessment. Patient exposure to alloantigen from another individual is a common occurrence and takes place through pregnancies, blood transfusions or previous transplantation. Such exposure to alloantigen's can lead to the formation of circulating alloreactive antibodies which can be deleterious to solid organ transplant outcome. The purpose of these guidelines is to update to the previous BSHI/BTS guidelines 2016 on the relevance, assessment, and management of alloantibodies within solid organ transplantation.
Collapse
Affiliation(s)
- Richard Battle
- Scottish National Blood Transfusion Service, Edinburgh, UK
| | | | - Sarah Peacock
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | | | - Sue Jordan
- National Blood Service Tooting, London, UK
| | | | - Martin Barnardo
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Rebecca Cope
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | | | | | - Luke Foster
- Birmingham Blood Donor Centre, Birmingham, UK
| | | | - Olivia Shaw
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - David Turner
- Scottish National Blood Transfusion Service, Edinburgh, UK
| | - Arthi Anand
- Imperial College Healthcare NHS Trust, London, UK
| | | | | |
Collapse
|
|
11
|
Vianna R, Gaynor JJ, Selvaggi G, Farag A, Garcia J, Tekin A, Tabbara MM, Ciancio G. Liver Inclusion Appears to Be Protective Against Graft Loss-Due-to Chronic But Not Acute Rejection Following Intestinal Transplantation. Transpl Int 2023; 36:11568. [PMID: 37779512 PMCID: PMC10538304 DOI: 10.3389/ti.2023.11568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 08/28/2023] [Indexed: 10/03/2023]
Abstract
In intestinal transplantation, while other centers have shown that liver-including allografts have significantly more favorable graft survival and graft loss-due-to chronic rejection (CHR) rates, our center has consistently shown that modified multivisceral (MMV) and full multivisceral (MV) allografts have significantly more favorable acute cellular rejection (ACR) and severe ACR rates compared with isolated intestine (I) and liver-intestine (LI) allografts. In the attempt to resolve this apparent discrepancy, we performed stepwise Cox multivariable analyses of the hazard rates of developing graft loss-due-to acute rejection (AR) vs. CHR among 350 consecutive intestinal transplants at our center with long-term follow-up (median: 13.5 years post-transplant). Observed percentages developing graft loss-due-to AR and CHR were 14.3% (50/350) and 6.6% (23/350), respectively. Only one baseline variable was selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to AR: Transplant Type MMV or MV (p < 0.000001). Conversely, two baseline variables were selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to CHR: Received Donor Liver (LI or MV) (p = 0.002) and Received Induction (p = 0.007). In summary, while MMV/MV transplants (who receive extensive native lymphoid tissue removal) offered protection against graft loss-due-to AR, liver-containing grafts appeared to offer protection against graft loss-due-to CHR, supporting the results of other studies.
Collapse
Affiliation(s)
- Rodrigo Vianna
- Department of Surgery, Miami Transplant Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Jeffrey J. Gaynor
- Department of Surgery, Miami Transplant Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Gennaro Selvaggi
- Department of Surgery, Miami Transplant Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Ahmed Farag
- Department of Surgery, Miami Transplant Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
- Department of Surgery, Zagazig University School of Medicine, Zagazig, Egypt
| | - Jennifer Garcia
- Department of Pediatrics, Miami Transplant Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Akin Tekin
- Department of Surgery, Miami Transplant Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Marina M. Tabbara
- Department of Surgery, Miami Transplant Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Gaetano Ciancio
- Department of Surgery, Miami Transplant Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| |
Collapse
|
|
12
|
Weiner J, Llore N, Ormsby D, Fujiki M, Segovia MC, Obri M, Jafri SM, Liggett J, Kroemer AH, Matsumoto C, Moon J, Di Cocco P, Selvaggi G, Garcia J, Ganoza A, Khanna A, Mazariegos G, Wendel D, Reyes J. The First Collective Examination of Immunosuppressive Practices Among American Intestinal Transplant Centers. Transplant Direct 2023; 9:e1512. [PMID: 37636483 PMCID: PMC10455426 DOI: 10.1097/txd.0000000000001512] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 05/23/2023] [Indexed: 08/29/2023] Open
Abstract
BACKGROUND Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices. METHODS All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed. RESULTS Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21.1). Induction regimens varied widely. Thymoglobulin was the most common, used in the plurality of patients (85/211; 40.3%), but there was no consensus regimen. Similarly, regimens for the treatment of acute cellular rejection, antibody-mediated rejection, and graft-versus-host disease varied significantly between centers. We also evaluated differences in maintenance immunosuppression protocols, desensitization regimens, mammalian target of rapamycin use, antimetabolite use, and posttransplantation surveillance practices. Maintenance tacrolimus levels, stoma presence, and scoping frequency were not associated with differences in rejection events. Definitive association between treatments and outcomes, including graft and patient survival, was not the intention of this initial collaboration and is prevented by the lack of patient-level data and the presence of confounders. However, we identified trends regarding rejection episodes after various induction strategies that require further investigation in our subsequent collaborations. CONCLUSIONS This initial collaboration reveals the extreme heterogeneity of practices among American ITx centers. Future collaboration will explore patient-level data, stratified by age and transplant type (isolated intestine versus multivisceral), to explore the association between treatment regimens and outcomes.
Collapse
Affiliation(s)
- Joshua Weiner
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY
| | - Nathaly Llore
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY
| | - Dylan Ormsby
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY
| | - Masato Fujiki
- Department of Surgery, Cleveland Clinic, Cleveland, OH
| | | | - Mark Obri
- Department of Medicine, Henry Ford Hospital, Detroit, MI
| | | | | | | | - Cal Matsumoto
- MedStar Georgetown Transplant Institute, Washington, DC
| | - Jang Moon
- Department of Surgery, Mount Sinai Medical Center, New York, NY
| | | | - Gennaro Selvaggi
- Miami Transplant Institute, University of Miami Jackson Memorial Hospital, Miami, FL
| | - Jennifer Garcia
- Miami Transplant Institute, University of Miami Jackson Memorial Hospital, Miami, FL
| | - Armando Ganoza
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Ajai Khanna
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - George Mazariegos
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Danielle Wendel
- Departments of Surgery and Pediatrics, University of Washington Medical Center/Seattle Children’s Hospital, Seattle, WA
| | - Jorge Reyes
- Departments of Surgery and Pediatrics, University of Washington Medical Center/Seattle Children’s Hospital, Seattle, WA
| |
Collapse
|
|
13
|
Chang YT, Soltys K, Khanna A, Bond GJ, Ganoza A, Rudolph JA, Sindhi R, Mazariegos GV. Long-term outcomes of intestinal transplantation from donors aged under 1 year. Pediatr Transplant 2022; 26:e14257. [PMID: 35195934 DOI: 10.1111/petr.14257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 01/07/2022] [Accepted: 02/05/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND The aim of the study was to analyze the long-term outcomes of transplants utilizing ITx donors <1 year and to compare these results with older donors. METHODS Between January 2007 and December 2019, the primary ITx donors in the Children's Hospital of Pittsburgh of UPMC were retrospectively reviewed. Short- and long-term outcomes of recipients receiving a deceased donor organ from donors <1 year were compared with those found in all other recipients. RESULTS During the study period, there were 89 primary ITx donors, using 30 donors (33.7%) aged <1 year. The mean age of their recipients was 1.6 ± 0.7 (0.7-3.2) years. The 30 graft types were isolated intestine (n = 3, 10.0%), liver bowel (n = 20, 66.7%), and multivisceral (n = 7, 23.3%). Technical complications occurred in 12 (40.0%) recipients. Candidates transplanted with intestine allografts from donors <1 year of age had shorter wait times (p < .001), more liver-inclusive grafts (p < .001), and less donor-specific antibodies (DSA) (p = .014). During follow-up, the recipients had less graft loss (p = .018), and more remained alive with graft in place (p = .011). Among children transplanted with such donors, 3-year and graft survival rates were 86.7% and 82.9% compared to 62.8% and 49.9% in the cohort of donors >1 year (p = .032 and .011). CONCLUSIONS Donor age <1 year was associated with improved graft survival. Optimal utilization of this population for toddler candidates would increase intestine availability, reduce time to transplantation, and potentially improve long-term outcome.
Collapse
Affiliation(s)
- Yu-Tang Chang
- Division of Pediatric Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Division of Pediatric Transplantation, Department of Surgery, Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA
| | - Kyle Soltys
- Division of Pediatric Transplantation, Department of Surgery, Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA
| | - Ajai Khanna
- Division of Pediatric Transplantation, Department of Surgery, Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA
| | - Geoffrey J Bond
- Division of Pediatric Transplantation, Department of Surgery, Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA
| | - Armando Ganoza
- Division of Pediatric Transplantation, Department of Surgery, Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA
| | - Jeffrey A Rudolph
- Division of Gastroenterology, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA
| | - Rakesh Sindhi
- Division of Pediatric Transplantation, Department of Surgery, Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA
| | - George V Mazariegos
- Division of Pediatric Transplantation, Department of Surgery, Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA
| |
Collapse
|
|
14
|
Current review on the role of ileostomy following intestinal transplantation. Curr Opin Organ Transplant 2022; 27:126-130. [DOI: 10.1097/mot.0000000000000966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
15
|
Moon JI, Ko HM, Iyer KR. Enhanced virtual crossmatch in intestinal transplantation: association with outcomes and application in practice. KOREAN JOURNAL OF TRANSPLANTATION 2021; 35:230-237. [PMID: 35769851 PMCID: PMC9235456 DOI: 10.4285/kjt.21.0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/19/2021] [Accepted: 12/06/2021] [Indexed: 11/04/2022] Open
Affiliation(s)
- Jang Il Moon
- Recanati Miller Transplantation Institute and Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Huaibin M Ko
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Kishore R Iyer
- Recanati Miller Transplantation Institute and Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| |
Collapse
|
|
16
|
Spaggiari M, Lichvar A, Tzvetanov I, Carroll R, Gaitonde S, Setty S, Cocco PD, Alvarez JAA, Benedetti E. Temporary Deceased Donor Splenic Transplant Prior to Intestinal Transplantation: A New Strategy for Desensitization? Transplant Proc 2021; 53:2602-2608. [PMID: 34503818 DOI: 10.1016/j.transproceed.2021.08.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 08/07/2021] [Indexed: 11/24/2022]
Abstract
Intestinal transplantation is a therapeutic treatment option for patients with irreversible intestinal failure. The presence of donor-specific antibodies (DSAs) has been associated with increased antibody-mediated rejection and allograft loss for recipients of all the solid organ transplants. This case report describes the posttransplant course in the first year of a patient who received a T-cell and B-cell flow cross-match (FXM) and complement-dependent cytotoxicity cross-match positive intestinal transplant in the presence of several class I and class II DSAs who underwent a "temporary desensitization" using the donor spleen. The temporary donor splenic transplant removed several class I and II DSAs as demonstrated by the negative subsequent T-cell FXM, the decreased mean channel shift of the positive B-cell FXM with a significant decrease in DSA mean florescence intensity post temporary splenic transplant. The patient experienced an isolated incidence of acute rejection, which responded to therapy. He had no infectious or cancerous sequelae from the immunosuppression modalities. He was able to discontinue total parenteral nutrition and gained weight after the procedure. Long-term effects are not able to be determined from this approach; hence, further research is warranted to better evaluate the real efficacy of this strategy.
Collapse
Affiliation(s)
- Mario Spaggiari
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois.
| | - Alicia Lichvar
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois; Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, Illinois
| | - Ivo Tzvetanov
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Robert Carroll
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Sujata Gaitonde
- Department of Pathology, University of Illinois at Chicago, Chicago, Illinois
| | - Suman Setty
- Department of Pathology, University of Illinois at Chicago, Chicago, Illinois
| | - Pierpaolo Di Cocco
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Jorge A Almario Alvarez
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Enrico Benedetti
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
| |
Collapse
|
|
17
|
Smullin CP, Venick RS, Marcus EA, Naini BV, Farmer DG. REG3α is a novel biomarker that potentially correlates with acute allograft rejection after intestinal transplantation. Clin Transplant 2021; 35:e14378. [PMID: 34060679 DOI: 10.1111/ctr.14378] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/06/2021] [Accepted: 05/27/2021] [Indexed: 12/15/2022]
Abstract
Monitoring of intestinal allograft function remains a challenge. While frequent endoscopies and biopsies are the gold standard, no single biomarker exists to screen for intestinal transplant rejection. The novel REG3α, an antimicrobial peptide secreted by intestinal enterocytes and Paneth cells, has been associated with inflammatory bowel disease as well as intestinal graft versus host disease. Our aim was to identify and describe a role of REG3α in monitoring or predicting acute allograft rejection after intestinal transplantation (ITx). Since 2019, we have incorporated REG3α into the standard monitoring of patients after ITx. We conducted a retrospective analysis of a prospectively maintained IRB-approved database and present, herein, the results of 2 adults with irreversible intestinal failure who underwent isolated ITx under this monitoring protocol. Increases in REG3α corresponded with acute allograft rejection in both cases and preceded acute allograft rejection by 1 week in one of the cases. We describe REG3α as a non-invasive marker of acute allograft rejection after adult isolated ITx which not only corresponded with acute allograft rejection but also preceded histopathological changes by 1 week.
Collapse
Affiliation(s)
| | - Robert S Venick
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Elizabeth A Marcus
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Bita V Naini
- Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Douglas G Farmer
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| |
Collapse
|
|
18
|
Chan AP, Guerra MAR, Rossetti M, Hickey MJ, Venick RS, Marcus EA, McDiarmid SV, Farmer DG, Reed EF, Wozniak LJ. Non-HLA AT1R antibodies are highly prevalent after pediatric intestinal transplantation. Pediatr Transplant 2021; 25:e13987. [PMID: 33590644 PMCID: PMC8058288 DOI: 10.1111/petr.13987] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/30/2021] [Accepted: 02/02/2021] [Indexed: 12/16/2022]
Abstract
The role of angiotensin II type-1 receptor (AT1R) antibodies in intestinal transplantation (ITx) is unclear. The aims were 1) to identify the prevalence of AT1R antibodies in pediatric ITx, compared to pediatric intestinal failure (IF), and 2) to determine whether AT1R antibodies were associated with graft dysfunction. 46 serum samples from 25 ITx patients (3 isolated ITx, 22 liver-inclusive ITx) were collected during routine visits >6 months apart and during episodes of graft dysfunction as a result of infectious enteritis or rejection. For comparison, samples were collected from 7 IF control patients. AT1R antibodies were considered positive for levels >17 U/mL. The median (range) AT1R antibody level for ITx patients was 40.0 U/mL (7.2-40.0), compared to 7.0 U/mL (5.7-40.0) for IF patients (p = .02). There was a trend toward higher prevalence of AT1R antibodies in ITx compared with IF patients (68% versus 29%, p = .09). Among ITx patients, the prevalence of AT1R antibodies was not different between periods of active graft dysfunction and normal health (83% versus 67%, p = .31). For 16 patients with >2 samples, AT1R antibodies remained positive in 67% cases, developed in 14% cases, disappeared in 10% cases, and remained negative in 10% cases. The changes in AT1R antibodies did not correlate with de/sensitizing events. This is the first study of AT1R antibodies in pediatric ITx. AT1R antibodies are highly prevalent after ITx and may be triggered by immune activation associated with the transplant. However, their pathogenicity and clinical utility remain in question.
Collapse
Affiliation(s)
- Alvin P Chan
- Pediatric Gastroenterology, Hepatology and Nutrition, UCLA Mattel Children's Hospital and David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Marjorie-Anne R Guerra
- Pediatric Gastroenterology, Hepatology and Nutrition, UCLA Mattel Children's Hospital and David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Maura Rossetti
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Michelle J Hickey
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Robert S Venick
- Pediatric Gastroenterology, Hepatology and Nutrition, UCLA Mattel Children's Hospital and David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Elizabeth A Marcus
- Pediatric Gastroenterology, Hepatology and Nutrition, UCLA Mattel Children's Hospital and David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- VA Greater Los Angeles Health Care System, Los Angeles, CA, USA
| | - Suzanne V McDiarmid
- Pediatric Gastroenterology, Hepatology and Nutrition, UCLA Mattel Children's Hospital and David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Douglas G Farmer
- Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Elaine F Reed
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Laura J Wozniak
- Pediatric Gastroenterology, Hepatology and Nutrition, UCLA Mattel Children's Hospital and David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| |
Collapse
|
|
19
|
Abstract
PURPOSE OF REVIEW In this article, data from the intestinal transplant registry, recent publications and reviews in the field will be used to describe mortality, morbidity, complications, nutritional and psychosocial outcomes in intestinal transplant recipients with a focus on those furthest out from transplant. RECENT FINDINGS Registry data show static long-term survival data (41% 10-year survival in the most recent analysis), but experienced centres report improvements with survival between 60 and 70% at 10 years. Chronic rejection remains a problem for long-term graft survival, but understanding of humoral immunity is increasing. Nutritional outcomes are good with most recipients achieving enteral autonomy with an unrestricted diet. Health-related quality of life data generally shows improvement in the years after transplant, educational attainment is good, but some patients have ongoing psychosocial problems. SUMMARY Most patients do well in the long-term after transplant. Survival outcomes have improved in experienced centres, and nutrition and quality of life outcomes are good. Recognition of psychosocial outcomes is increasing. Nevertheless, challenges remain in areas such as infectious complications, renal function, chronic rejection, social support and mental health.
Collapse
|
|
20
|
Abstract
PURPOSE OF REVIEW The current review aims to describe in detail the most common practices utilized to monitor graft function in intestinal transplant (ITx) recipients. In addition, to discussing the role of endoscopy and stool studies it will examine the use of other potential biomarkers which have been utilized. Data will be discussed from contemporary publications in the field, the Intestinal Transplant Registry as well as detailed data from a large, ITx single-center. RECENT FINDINGS Significant improvements have been made in early outcomes following ITx, yet long-term survival remains challenged by infection and rejection, both of which can present with diarrhea. While endoscopy and stool studies are the gold-standard for graft monitoring, calprotectin, citrulline, measurements of immunoreactivity and donor-specific antibodies have been investigated in the field and are herein reviewed. SUMMARY Despite a number of tests which are currently available for monitoring ITx recipients, a strong need exists for improved noninvasive, timely and accurate biomarkers to help improve ITx graft and patient survival.
Collapse
|
|
21
|
Current status of pediatric intestinal transplantation in the United States. Curr Opin Organ Transplant 2020; 25:201-207. [PMID: 32073484 DOI: 10.1097/mot.0000000000000744] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW The present review aims to describe in detail the characteristics, outcomes, and recent trends in the field of pediatric intestinal transplantation in the United States. It will examine the route cause and future implications of these developments. The review will draw from recent publications in the field, the Intestinal Transplant Registry, and contemporary data from large U.S. single centers. RECENT FINDINGS More than 1500 pediatric intestinal transplants have been performed in the United States since 1985, however, over the past decade there have been fewer than 50 transplants/year nationwide. This trend is largely a result of stagnant long-term ITx outcomes and advancements in intestinal rehabilitation programs. Nationally the overall 1-year and 5-year graft survival are 68 and 50% respectively, whereas certain high-volume centers have experienced significantly better results. Sepsis is the leading cause of death following pediatric ITx, whereas rejection is the leading cause of graft loss. Chronic kidney disease and posttransplant lymphoproliferative disorder are significant and relatively prevalent long-term complications. The majority of pediatric ITx recipients receive T-cell depleting induction agents and are on Tacrolimus-based immunosuppression. Most recipient are off parenteral nutrition, but may require supplemental tube feeds. Many pediatric ITx recipients require special education, and in certain domains some report lower health related quality of life. SUMMARY As intestinal rehabilitation has improved in the modern era, the volume of pediatric ITx in the United States has decreased. Although pediatric ITx results have room for improvement nationwide, successful outcomes have been reported at experienced American centers.
Collapse
|
|
22
|
Raghu VK, Beaumont JL, Everly MJ, Venick RS, Lacaille F, Mazariegos GV. Pediatric intestinal transplantation: Analysis of the intestinal transplant registry. Pediatr Transplant 2019; 23:e13580. [PMID: 31531934 PMCID: PMC6879795 DOI: 10.1111/petr.13580] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 08/16/2019] [Accepted: 08/20/2019] [Indexed: 12/30/2022]
Abstract
The ITR serves as an international database for centers around the world to contribute to current knowledge about intestinal transplant outcomes. Led by the IRTA and managed by the Terasaki Research Institute, the ITR collects data annually and uses these data to generate reports that guide management strategies and policy statements. The aim of this manuscript was to analyze outcomes specific to pediatric intestinal transplantation. Outcome data for children transplanted from 1985 to 2017 were analyzed and predictive factors assessed. A total of 2010 children received 2080 intestine containing allografts during this period. Overall, 1-year and 5-year patient and graft survival were 72.7%/66.1% and 57.2/48.8%, respectively. One-year conditional survival was most strongly associated with being a first-time transplant recipient and liver-inclusive grafts. Patient survival was most strongly associated with elective status of transplantation as compared with hospitalized status. Enteral autonomy following transplantation has continued to improve by era with colonic inclusion demonstrating additional incremental improvement in enteral autonomy and freedom from intravenous fluid. While PTLD and technical complications contribute less to graft loss than in earlier eras, rejection remains the largest contributor to long-term graft loss. Re-transplantation is linked with significantly worse conditional graft survival, and sepsis remains the largest contributor to patient death. Newer data elements are focusing on impact of donor variables, donor and recipient tissue typing, and impact of the development of de novo antibodies.
Collapse
Affiliation(s)
- Vikram K. Raghu
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA
| | | | | | - Robert S. Venick
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, David Geffen School of Medicine, UCLA, Los Angeles, CA
| | - Florence Lacaille
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Hôpital Necker Enfants Malades, 75015 Paris, France
| | - George V. Mazariegos
- Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA
| |
Collapse
|
|
23
|
Generating an Artificial Intestine for the Treatment of Short Bowel Syndrome. Gastroenterol Clin North Am 2019; 48:585-605. [PMID: 31668185 DOI: 10.1016/j.gtc.2019.08.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Intestinal failure is defined as the inability to maintain fluid, nutrition, energy, and micronutrient balance that leads to the inability to gain or maintain weight, resulting in malnutrition and dehydration. Causes of intestinal failure include short bowel syndrome (ie, the physical loss of intestinal surface area and severe intestinal dysmotility). For patients with intestinal failure who fail to achieve enteral autonomy through intestinal rehabilitation programs, the current treatment options are expensive and associated with severe complications. Therefore, the need persists for next-generation therapies, including cell-based therapy, to increase intestinal regeneration, and development of the tissue-engineered small intestine.
Collapse
|
|
24
|
Infectious Complications in Home Parenteral Nutrition: A Systematic Review and Meta-Analysis Comparing Peripherally-Inserted Central Catheters with Other Central Catheters. Nutrients 2019; 11:nu11092083. [PMID: 31487777 PMCID: PMC6770172 DOI: 10.3390/nu11092083] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 08/24/2019] [Accepted: 08/29/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Home parenteral nutrition (HPN) has become a common therapy. There is still controversy regarding the possibility that peripherally inserted central catheters (PICCs) may diminish catheter-related blood stream infection (CRBSI) rates. Methods: We searched the PubMed database for studies reporting the rates of CRBSI with HPN. Study selection was performed independently by three investigators. Disagreements were discussed and resolved by consensus or by arbitration by an author not involved in the search. The National Institutes of Health Quality Assessment Tools was used to assess the methodological quality of the studies. Meta-analyses were performed using MetaXL 5.3 with the quality effects model. Results: Screening of the article titles and abstracts yielded 134 full text articles for evaluation. Only three prospective studies that included appropriate data were considered for the final analysis. The relative risk of the CRBSI rate was 0.41 (0.14–1.17) for PICC vs. tunneled catheters. The relative risk of the CRBSI rate was 0.16 (0.04–0.64) for PICC vs. ports. The relative risk of the thrombosis rate was 3.16 (0.20–49.67) for PICCs vs. tunneled. Conclusions: There is insufficient evidence to show a difference in CRBSI rates between PICCs and tunneled catheters. On the other hand, PICCs showed lower CRBSI rates than ports. There was also no difference in the rate of catheter-related thrombosis and mechanical complications.
Collapse
|
|
25
|
Ileostomy After Intestinal Transplantation: The First in Depth Report on Techniques, Complications, and Outcomes. Transplantation 2019; 104:652-658. [PMID: 31335764 DOI: 10.1097/tp.0000000000002879] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Temporary ileostomy during intestinal transplantation (ITx) is the standard technique for allograft monitoring. A detailed analysis of the ITx ileostomy has never been reported. METHODS A retrospective review of a single-center ITx database was performed. The analysis was divided into ileostomy formation and takedown episodes. RESULTS One hundred thirty-five grafts underwent ileostomy formation, and 79 underwent ileostomy takedown. Median age at ITx was 7.7 years and weight was 23 kg. Allograft types were intestine (22%), liver/intestine (55%), multivisceral (16%), and modified multivisceral (7%). Sixty-four percent had 1-stage ITx, whereas 36% required 2-staged ITx. Final ileostomy types were end (20%), loop (10%), distal blowhole (59%), and proximal blowhole (11%). Ileostomy formation: Thirty-one grafts had complications (23%), including prolapse (26%), ischemia (16%), and parastomal hernia (19%). Twelve required surgical revision. There were no significant differences in graft type, ileostomy type, survival, and ileostomy takedown rate between grafts with and without complications. Colon inclusive grafts had higher complication rates (P = 0.002). Ileostomy takedown: Ileostomy takedown occurred at a median of 422 days post-ITx. Twenty-five complications occurred after 22 takedowns (28%), including small bowel obstruction (27%) and abscess (18%). Fifteen grafts required surgical correction. Recipients with complications had longer hospital stay (17 versus 9 d; P = 0.001) than those without complications. Graft type, ileostomy type, and survival were not different. CONCLUSIONS The first of its kind analysis of the surgical ileostomy after ITx reveals that most recipients can undergo successful ileostomy formation/takedown, complication rates are significant but within an acceptable range, and complications do not affect survival. This study demonstrates that the routine use of transplant ostomies remains an acceptable practice after ITx. However, true analysis of risk and benefit will require a randomized control trial.
Collapse
|
|
26
|
Elsabbagh AM, Hawksworth J, Khan KM, Kaufman SS, Yazigi NA, Kroemer A, Smith C, Fishbein TM, Matsumoto CS. Long-term survival in visceral transplant recipients in the new era: A single-center experience. Am J Transplant 2019; 19:2077-2091. [PMID: 30672105 PMCID: PMC6591067 DOI: 10.1111/ajt.15269] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 12/31/2018] [Accepted: 01/14/2019] [Indexed: 02/06/2023]
Abstract
There is a paucity of data on long-term outcomes following visceral transplantation in the contemporary era. This is a single-center retrospective analysis of all visceral allograft recipients who underwent transplant between November 2003 and December 2013 with at least 3-year follow-up data. Clinical data from a prospectively maintained database were used to assess outcomes including patient and graft survival. Of 174 recipients, 90 were adults and 84 were pediatric patients. Types of visceral transplants were isolated intestinal transplant (56.3%), combined liver-intestinal transplant (25.3%), multivisceral transplant (16.1%), and modified multivisceral transplant (2.3%). Three-, 5-, and 10-year overall patient survival was 69.5%, 66%, and 63%, respectively, while 3-, 5-, and 10-year overall graft survival was 67%, 62%, and 61%, respectively. In multivariable analysis, significant predictors of survival included pediatric recipient (P = .001), donor/recipient weight ratio <0.9 (P = .008), no episodes of severe acute rejection (P = .021), cold ischemia time <8 hours (P = .014), and shorter hospital stay (P = .0001). In conclusion, visceral transplantation remains a good option for treatment of end-stage intestinal failure with parenteral nutritional complications. Proper graft selection, shorter cold ischemia time, and improvement of immunosuppression regimens could significantly improve the long-term survival.
Collapse
Affiliation(s)
- Ahmed M. Elsabbagh
- MedStar Georgetown Transplant Institute, Georgetown University Hospital, Washington, DC,Gastroenterology Surgical Center, Department of Surgery, Mansoura University, Mansoura, Egypt,St. Vincent Abdominal Transplant Center, St. Vincent Hospital, Indianapolis, Indiana
| | - Jason Hawksworth
- MedStar Georgetown Transplant Institute, Georgetown University Hospital, Washington, DC,Department of Surgery, Organ Transplant Service, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Khalid M. Khan
- MedStar Georgetown Transplant Institute, Georgetown University Hospital, Washington, DC
| | - Stuart S. Kaufman
- MedStar Georgetown Transplant Institute, Georgetown University Hospital, Washington, DC
| | - Nada A. Yazigi
- MedStar Georgetown Transplant Institute, Georgetown University Hospital, Washington, DC
| | - Alexander Kroemer
- MedStar Georgetown Transplant Institute, Georgetown University Hospital, Washington, DC
| | - Coleman Smith
- MedStar Georgetown Transplant Institute, Georgetown University Hospital, Washington, DC
| | - Thomas M. Fishbein
- MedStar Georgetown Transplant Institute, Georgetown University Hospital, Washington, DC
| | - Cal S. Matsumoto
- MedStar Georgetown Transplant Institute, Georgetown University Hospital, Washington, DC
| |
Collapse
|
|
27
|
Wozniak LJ, Venick RS. Donor-specific antibodies following liver and intestinal transplantation: Clinical significance, pathogenesis and recommendations. Int Rev Immunol 2019; 38:106-117. [DOI: 10.1080/08830185.2019.1630404] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Laura J. Wozniak
- Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Robert S. Venick
- Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| |
Collapse
|
|
28
|
Donor-specific antibody management in intestine transplantation: hope for improving the long-term durability of the intestine allograft? Curr Opin Organ Transplant 2019; 24:212-218. [DOI: 10.1097/mot.0000000000000619] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
|
|
29
|
|
|
30
|
Dumronggittigule W, Marcus EA, DuBray BJ, Venick RS, Dutson E, Farmer DG. Intestinal failure after bariatric surgery: Treatment and outcome at a single-intestinal rehabilitation and transplant center. Surg Obes Relat Dis 2019; 15:98-108. [PMID: 30658947 DOI: 10.1016/j.soard.2018.10.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 10/15/2018] [Accepted: 10/18/2018] [Indexed: 11/27/2022]
Abstract
BACKGROUND Though intestinal failure (IF) after bariatric surgery (BS) is uncommon, its prevalence is increasing. However, data on the outcomes for these patients are limited. OBJECTIVES To analyze the outcomes of treatment for patients with IF after BS. SETTING University hospital. METHODS A single-center analysis (1991-2016) of outcomes according to treatment arms established by a multidisciplinary team. RESULTS Twenty-five IF patients were identified (median age 45 yr). BS was 92% Roux-en-Y gastric bypass. The major cause of IF was volvulus/internal hernia (72%). Median time from BS to IF was 48 months. Treatment arms were intestinal rehabilitation (IR, n = 15), transplantation (TXP, n = 5), and parenteral nutrition (PN, n = 5). For IR, median bowel length was 60 cm. Forty-six percent ultimately discontinued PN. Twenty-seven percent were partially weaned PN and 27% failed IR. Common surgical rehabilitation was Roux-en-Y gastric bypass reversal and restoration of gastrointestinal continuity. The 5-year overall survival was 74%. For TXP, 7 patients were listed for TXP (5 initially and 2 after failed IR). Three underwent TXP, 2 isolated intestine and 1 isolated liver. Three were delisted (1 improvement and 2 death). For PN, 6 patients required long-term PN (5 initially and 1 after failed IR). Four patients are alive currently. CONCLUSIONS IF after BS is an increasing problem facing IR centers. Internal hernia is the major cause. Surgical IR is the first-line therapy and affords the best outcome. TXP is reserved for rescuing patients who failed IR or develop PN complications. Long-term PN is suitable for patients in whom IR or TXP is impractical.
Collapse
Affiliation(s)
- Wethit Dumronggittigule
- The Dumont UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California; Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Nakhon Pathom, Thailand
| | - Elizabeth A Marcus
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Mattel Children's Hospital, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California; VA Greater Los Angeles Healthcare System, Los Angeles, California
| | - Bernard J DuBray
- The Dumont UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California
| | - Robert S Venick
- Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Nakhon Pathom, Thailand
| | - Erik Dutson
- Division of General Surgery, Department of Surgery, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California
| | - Douglas G Farmer
- The Dumont UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California.
| |
Collapse
|
|
31
|
Talayero P, Ramos Boluda E, Gómez Massa E, Castro Panete MJ, Prieto Bozano G, Hernández Oliveros F, López Santamaría M, Calvo Pulido J, Paz-Artal E, Mancebo E. Donor-Specific Antibodies in Pediatric Intestinal and Multivisceral Transplantation: The Role of Liver and Human Leukocyte Antigen Mismatching. Liver Transpl 2018; 24:1726-1735. [PMID: 30112820 DOI: 10.1002/lt.25323] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 08/07/2018] [Indexed: 01/13/2023]
Abstract
Rejection is one of the most important drawbacks for graft and patient survival in intestinal and multivisceral transplantation. However, there is no consensus on the diagnostic criteria for humoral rejection, and the literature about the role of donor-specific antibodies (DSA) on allograft outcome and the risk factors that contribute to their development is scant with contradictory results. The present study analyzes the role of DSA exclusively in a pediatric cohort of 43 transplants. Among our patients, 11.6% showed preformed DSA, but they did not correlate with more rejection or less allograft survival. Having previous transplants was the main sensitization factor with an odds ratio (OR) = 44.85 (P = 0.001). In total, 16.3% of recipients developed de novo donor-specific antibodies (dnDSA), mostly directed against human leukocyte antigen (HLA) class II, polyspecific and complement fixing. Additionally, the presence of dnDSA had a deleterious effect on graft rejection (hazard ratio [HR] = 11.00; P = 0.01) and survival (HR = 66.52; P < 0.001) in an observational period of 5 years after transplantation. The inclusion of the liver emerged as the main protective factor against dnDSA development with an OR = 0.07 (P = 0.007). The analysis of HLA compatibility at the serological and epitope level with the computational tools HLAMatchmaker and PIRCHE revealed no association between HLA mismatching and dnDSA. In conclusion, this study performed in pediatric recipients shows the deleterious effect of dnDSA on intestinal transplantation supported by the complement-fixing activity observed. Additionally, the liver inclusion in the allografts showed to be a protective factor against dnDSA generation.
Collapse
Affiliation(s)
- Paloma Talayero
- Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain.,I+12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
| | - Esther Ramos Boluda
- Pediatric Gastroenterology Intestinal Rehabilitation Unit, University Hospital La Paz, Madrid, Spain
| | - Elena Gómez Massa
- Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain.,I+12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
| | | | - Gerardo Prieto Bozano
- Pediatric Gastroenterology Intestinal Rehabilitation Unit, University Hospital La Paz, Madrid, Spain
| | - Francisco Hernández Oliveros
- Department of Pediatric Surgery, University Hospital La Paz, Madrid, Spain.,EOC of ERN-Transplantchild, University Hospital La Paz, Madrid, Spain
| | | | - Jorge Calvo Pulido
- General and Digestive Surgery and Abdominal Organ Transplantation, University Hospital 12 de Octubre, Madrid, Spain.,School of Medicine, Complutense University, Madrid, Spain
| | - Estela Paz-Artal
- Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain.,I+12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain.,School of Medicine, Complutense University, Madrid, Spain.,Section of Immunology, San Pablo CEU University, Madrid, Spain
| | - Esther Mancebo
- Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain.,I+12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain.,School of Medicine, Complutense University, Madrid, Spain
| |
Collapse
|
|
32
|
Celik N, Stanley K, Rudolph J, Al-Issa F, Kosmach B, Ashokkumar C, Sun Q, Brown-Bakewell R, Zecca D, Soltys K, Khanna A, Bond G, Ganoza A, Mazariegos G, Sindhi R. Improvements in intestine transplantation. Semin Pediatr Surg 2018; 27:267-272. [PMID: 30342602 DOI: 10.1053/j.sempedsurg.2018.07.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Transplantation of the intestine in children has presented significant challenges even as it has become a standard to treat nutritional failure due to short gut syndrome. These challenges have been addressed in part by significant improvements in short and long-term care. Noteworthy enhancements include reduced need for intestine transplantation, drug-sparing immunosuppressive regimens, immune monitoring, and improved surveillance and management of PTLD and non-adherence.
Collapse
Affiliation(s)
- Neslihan Celik
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - Kaitlin Stanley
- Division of Pediatric Hematology/Oncology, Children's Hospital of Pittsburgh of UPMC, USA
| | - Jeff Rudolph
- Intestinal Care and Rehabilitation Center, Children's Hospital of Pittsburgh of UPMC, USA
| | - Feras Al-Issa
- Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of UPMC, USA
| | - Beverly Kosmach
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - Chethan Ashokkumar
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - Qing Sun
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - Renee Brown-Bakewell
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - Dale Zecca
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - Kyle Soltys
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - Ajai Khanna
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - Geoffrey Bond
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - Armando Ganoza
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - George Mazariegos
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
| | - Rakesh Sindhi
- Thomas E Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA.
| |
Collapse
|
|
33
|
Santacruz E, Mateo-Lobo R, Riveiro J, Nattero L, Vega-Piñero B, Lomba G, Sabido R, Carabaña F, Arrieta FJ, Botella-Carretero JI. Infectious complications in home parenteral nutrition: A long-term study with peripherally inserted central catheters, tunneled catheters, and ports. Nutrition 2018; 58:89-93. [PMID: 30391696 DOI: 10.1016/j.nut.2018.06.016] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 05/27/2018] [Accepted: 06/11/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Home parenteral nutrition (HPN) has become a common therapy, with tunneled central venous catheters (CVCs) being the preferred route of administration. Peripherally inserted central catheters (PICCs) have been used increasingly, but whether they should be preferred over other types of CVCs is still controversial. The aim of this study was to evaluate catheter-related complications of CVC in patients receiving HPN. METHODS All patients treated at our center for HPN from 2007 to 2017 were prospectively included. A specialized intravenous therapy team took care of these patients. Catheter-related bloodstream infections (CRBSI) were confirmed with positive, simultaneous, differential blood cultures drawn through the CVC and peripheral vein and then semiquantitative or quantitative culture of the catheter tip. RESULTS = 6.625, P = 0.036) were more frequent with multilumen catheters. CONCLUSIONS In our setting, single-lumen PICC and Hickman catheters showed low infectious complications.
Collapse
Affiliation(s)
- Elisa Santacruz
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Raquel Mateo-Lobo
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Javier Riveiro
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Lia Nattero
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Belén Vega-Piñero
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Gema Lomba
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Raquel Sabido
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Fátima Carabaña
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Francisco J Arrieta
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Madrid, Spain
| | - Jose I Botella-Carretero
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Madrid, Spain.
| |
Collapse
|
|
34
|
Wozniak LJ, Mauer TL, Venick RS, Said JW, Kao RL, Kempert P, Marcus EA, Hwang V, Cheng EY, Busuttil RW, McDiarmid SV, Farmer DG. Clinical characteristics and outcomes of PTLD following intestinal transplantation. Clin Transplant 2018; 32:e13313. [DOI: 10.1111/ctr.13313] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/06/2018] [Indexed: 12/23/2022]
Affiliation(s)
- Laura J. Wozniak
- Pediatric Gastroenterology, Hepatology, and Nutrition; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| | - Tian L. Mauer
- Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| | - Robert S. Venick
- Pediatric Gastroenterology, Hepatology, and Nutrition; David Geffen School of Medicine at UCLA; Los Angeles CA USA
- Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| | - Jonathan W. Said
- Department of Pathology and Laboratory Medicine; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| | - Roy L. Kao
- Pediatric Hematology and Oncology; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| | - Pamela Kempert
- Pediatric Hematology and Oncology; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| | - Elizabeth A. Marcus
- Pediatric Gastroenterology, Hepatology, and Nutrition; David Geffen School of Medicine at UCLA; Los Angeles CA USA
- VA Greater Los Angeles Health Care System; Los Angeles CA USA
| | - Vilayphone Hwang
- Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| | - Elaine Y. Cheng
- Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| | - Ronald W. Busuttil
- Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| | - Sue V. McDiarmid
- Pediatric Gastroenterology, Hepatology, and Nutrition; David Geffen School of Medicine at UCLA; Los Angeles CA USA
- Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| | - Douglas G. Farmer
- Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA; Los Angeles CA USA
| |
Collapse
|
|
35
|
|
|
36
|
Weissenbacher A, Vrakas G, Chen M, Reddy S, Allan P, Giele H, Barnardo MC, Vaidya A, Friend PJ, Fuggle SV. De novo
donor-specific HLA antibodies after combined intestinal and vascularized composite allotransplantation - a retrospective study. Transpl Int 2017; 31:398-407. [DOI: 10.1111/tri.13096] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 07/24/2017] [Accepted: 11/12/2017] [Indexed: 12/26/2022]
Affiliation(s)
- Annemarie Weissenbacher
- Oxford Transplant Centre; Nuffield Department of Surgical Sciences; Oxford University Hospitals; Churchill Hospital Oxford, UK
- Department of Visceral; Transplant and Thoracic Surgery; Innsbruck Medical University Innsbruck, Austria
| | - Georgios Vrakas
- Oxford Transplant Centre; Nuffield Department of Surgical Sciences; Oxford University Hospitals; Churchill Hospital Oxford, UK
| | - Mian Chen
- Oxford Transplant Centre; Nuffield Department of Surgical Sciences; Oxford University Hospitals; Churchill Hospital Oxford, UK
| | - Srikanth Reddy
- Oxford Transplant Centre; Nuffield Department of Surgical Sciences; Oxford University Hospitals; Churchill Hospital Oxford, UK
| | - Philip Allan
- Oxford Transplant Centre; Nuffield Department of Surgical Sciences; Oxford University Hospitals; Churchill Hospital Oxford, UK
- Translational Gastroenterology Unit; John Radcliffe Hospital; Oxford UK
| | - Henk Giele
- Department of Plastic and Reconstructive Surgery; John Radcliffe Hospital; Oxford UK
| | - Martin C.N.M Barnardo
- Oxford Transplant Centre; Nuffield Department of Surgical Sciences; Oxford University Hospitals; Churchill Hospital Oxford, UK
| | - Anil Vaidya
- Transplant Department; Apollo Hospitals Enterprise; Chennai India
| | - Peter J. Friend
- Oxford Transplant Centre; Nuffield Department of Surgical Sciences; Oxford University Hospitals; Churchill Hospital Oxford, UK
| | - Susan V. Fuggle
- Oxford Transplant Centre; Nuffield Department of Surgical Sciences; Oxford University Hospitals; Churchill Hospital Oxford, UK
| |
Collapse
|
|
37
|
Abstract
The diagnosis of irreversible intestinal failure confers significant morbidity, mortality, and decreased quality of life. Patients with irreversible intestinal failure may be treated with intestinal transplantation. Intestinal transplantation may include intestine only, liver-intestine, or other visceral elements. Intestinal transplantation candidates present with systemic manifestations of intestinal failure requiring multidisciplinary evaluation at an intestinal transplantation center. Central access may be difficult in intestinal transplantation candidates. Intestinal transplantation is a complex operation with potential for hemodynamic and metabolic instability. Patient and graft survival are improving, but graft failure remains the most common postoperative complication.
Collapse
Affiliation(s)
- Christine Nguyen-Buckley
- Department of Anesthesiology, David Geffen School of Medicine, University of California at Los Angeles, 757 Westwood Plaza, Suite 3304, Los Angeles, CA 90095, USA.
| | - Melissa Wong
- Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, 757 Westwood Plaza, Los Angeles, CA 90095, USA
| |
Collapse
|
|
38
|
Behnam Sani K, Sawitzki B. Immune monitoring as prerequisite for transplantation tolerance trials. Clin Exp Immunol 2017; 189:158-170. [PMID: 28518214 DOI: 10.1111/cei.12988] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/09/2017] [Indexed: 02/06/2023] Open
Abstract
Ever since its first application in clinical medicine, scientists have been urged to induce tolerance towards foreign allogeneic transplants and thus avoid rejection by the recipient's immune system. This would circumvent chronic use of immunosuppressive drugs (IS) and thus avoid development of IS-induced side effects, which are contributing to the still unsatisfactory long-term graft and patient survival after solid organ transplantation. Although manifold strategies of tolerance induction have been described in preclinical models, only three therapeutic approaches have been utilized successfully in a still small number of patients. These approaches are based on (i) IS withdrawal in spontaneous operational tolerant (SOT) patients, (ii) induction of a mixed chimerism and (iii) adoptive transfer of regulatory cells. Results of clinical trials utilizing these approaches show that tolerance induction does not work in all patients. Thus, there is a need for reliable biomarkers, which can be used for patient selection and post-therapeutic immune monitoring of safety, success and failure. In this review, we summarize recent achievements in the identification and validation of such immunological assays and biomarkers, focusing mainly on kidney and liver transplantation. From the published findings so far, it has become clear that indicative biomarkers may vary between different therapeutic approaches applied and organs transplanted. Also, patient numbers studied so far are very small. This is the main reason why nearly all described parameters lack validation and reproducibility testing in large clinical trials, and are therefore not yet suitable for clinical practice.
Collapse
Affiliation(s)
- K Behnam Sani
- Institute of Medical Immunology, Charité Universitaetsmedizin Berlin, Berlin, Germany
| | - B Sawitzki
- Institute of Medical Immunology, Charité Universitaetsmedizin Berlin, Berlin, Germany
| |
Collapse
|
|
39
|
Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal Transplant Recipients. Transplantation 2017; 101:873-882. [PMID: 27490417 DOI: 10.1097/tp.0000000000001391] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Rejection remains the leading cause of allograft loss, and a major barrier to improving long-term outcomes after intestinal transplantation. Our aim is to define the prevalence and investigate the role of donor-specific antibody (DSA) on intestinal graft outcomes. METHODS The study includes 109 transplants performed in 95 recipients at a single center. Patients were screened for DSA pretransplant, monitored regularly posttransplant and when clinically indicated using the single-antigen bead Luminex assay. Standard induction immunosuppression was with interleukin-2 receptor antagonists, and antithymocyte globulin in high-risk recipients. Maintenance regimens were tacrolimus-based. RESULTS Pretransplant DSA was detected in 12 (11%) recipients with 50% continuing to have circulating antibodies posttransplant. An additional 24 (25%) patients developed de novo DSA, and of these, 71% had persistent antibodies. Recipients with preformed DSA demonstrated elevated risks of early graft failure, whereas those with de novo DSA experienced accelerated graft loss once DSA was detected, reaching a 28% failure rate within 2 years. HLA-DQ mismatch is a significant risk factor for de novo DSA emergence, whereas the persistence of antibodies is predicted by DSA strength and specificity. Although inclusion of the liver in the intestinal allograft imparts an immunological advantage against rejection-related graft loss, this protective effect was lost among recipients with persistent DSA. CONCLUSIONS The presence of DSA is associated with inferior graft outcomes among intestinal transplant recipients. An enhanced understanding of the mechanisms by which DSA causes allograft injury, and effective strategies targeting humoral immune reactivity are needed to improve long-term intestinal graft outcomes.
Collapse
|
|
40
|
The impact of antibodies and virtual crossmatching on intestinal transplant outcomes. Curr Opin Organ Transplant 2017; 22:149-154. [DOI: 10.1097/mot.0000000000000393] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
41
|
Petit LM, Rabant M, Canioni D, Suberbielle-Boissel C, Goulet O, Chardot C, Lacaille F. Impacts of donor-specific anti-HLA antibodies and antibody-mediated rejection on outcomes after intestinal transplantation in children. Pediatr Transplant 2017; 21. [PMID: 28084679 DOI: 10.1111/petr.12847] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/24/2016] [Indexed: 11/28/2022]
Abstract
AMR is a risk factor for graft failure after SBTx. We studied impact of DSAs and AMR in 22 children transplanted between 2008 and 2012 (11 isolated SBTx, 10 liver inclusive Tx, and one modified multivisceral Tx). Three patients never developed DSA, but DSAs were found in seven in the pre-Tx period and de novo post-Tx in 19 children. Pathology revealed cellular rejection (15/19), with vascular changes and C4d+. Patients were treated with IV immunoglobulins, plasmapheresis, and steroids. Rescue therapy included antithymocyte globulins, rituximab, eculizumab, and bortezomib. Pathology and graft function normalized in 13 patients, graft loss occurred in two, and death in seven. At the end of the follow-up, 15 children were alive (68%), 13 with functioning graft (59%). Prognosis factors for poor outcome after Tx were the presence of symptoms at AMR suspicion (P +.033). DSAs were often found following SBTx, mostly de novo. Resistant ACR or severe AMR is still difficult to differentiate, with a high need for immunosuppression in both. DSAs may precede development of severe disease and pathology features on the graft: relationship and correlation need to be better investigated with larger groups before and after Tx.
Collapse
Affiliation(s)
- L-M Petit
- Unité d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpitaux Universitaires de Genève, Geneve, Switzerland
| | - M Rabant
- Service d'Anatomopathologie, Hôpital Necker Enfants Malades, Paris, France
| | - D Canioni
- Service d'Anatomopathologie, Hôpital Necker Enfants Malades, Paris, France
| | | | - O Goulet
- Service d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpital Necker Enfants Malades, Paris, France
| | - C Chardot
- Service de Chirurgie Viscérale Pédiatrique, Hôpital Necker Enfants Malades, Paris, France
| | - F Lacaille
- Service d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpital Necker Enfants Malades, Paris, France
| |
Collapse
|
|
42
|
Lacaille F, Irtan S, Dupic L, Talbotec C, Lesage F, Colomb V, Salvi N, Moulin F, Sauvat F, Aigrain Y, Revillon Y, Goulet O, Chardot C. Twenty-eight years of intestinal transplantation in Paris: experience of the oldest European center. Transpl Int 2017; 30:178-186. [DOI: 10.1111/tri.12894] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 10/31/2016] [Accepted: 11/20/2016] [Indexed: 01/19/2023]
Affiliation(s)
- Florence Lacaille
- Pediatric Gastroenterology-Hepatology-Nutrition; Necker-Enfants malades Hospital; Paris France
| | - Sabine Irtan
- Pediatric Surgery; Necker-Enfants malades Hospital; Paris France
| | - Laurent Dupic
- Pediatric Intensive Care; Necker-Enfants malades Hospital; Paris France
| | - Cécile Talbotec
- Pediatric Gastroenterology-Hepatology-Nutrition; Necker-Enfants malades Hospital; Paris France
| | - Fabrice Lesage
- Pediatric Intensive Care; Necker-Enfants malades Hospital; Paris France
| | - Virinie Colomb
- Pediatric Gastroenterology-Hepatology-Nutrition; Necker-Enfants malades Hospital; Paris France
| | - Nadège Salvi
- Anesthesiology; Necker-Enfants malades Hospital; Paris France
| | - Florence Moulin
- Pediatric Intensive Care; Necker-Enfants malades Hospital; Paris France
| | | | - Yves Aigrain
- Pediatric Surgery; Necker-Enfants malades Hospital; Paris France
| | - Yann Revillon
- Pediatric Surgery; Necker-Enfants malades Hospital; Paris France
| | - Olivier Goulet
- Pediatric Gastroenterology-Hepatology-Nutrition; Necker-Enfants malades Hospital; Paris France
| | | |
Collapse
|
|
43
|
Poole JA, Qiu F, Kalil AC, Grant W, Mercer DF, Florescu DF. Impact of Immunoglobulin Therapy in Intestinal Transplant Recipients With Posttransplantation Hypogammaglobulinemia. Transplant Proc 2017; 48:479-84. [PMID: 27109982 DOI: 10.1016/j.transproceed.2015.12.064] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 12/29/2015] [Indexed: 11/16/2022]
Abstract
BACKGROUND Severe hypogammaglobulinemia (HGG) (IgG <400 mg/dL) following intestinal transplantation is common. Although IgG replacement therapy is commonly used, clinical outcomes associated with increasing IgG levels to >400 mg/dL are not well described. METHODS Kaplan-Meier analysis was performed to estimate survival, the log-rank test to compare survival distributions between groups, and the Fisher exact test to determine the association between HGG and rejection. RESULTS A total of 23 intestinal transplant (IT) recipients with a median age of 2.3 years (range, 0.7-41 years) at the time of HGG diagnosis were included. The types of transplants were liver-small bowel (73.9%), liver-small bowel-kidney (8.7%), and small bowel only (17.4%). The 3-year survival after the diagnosis of HGG was 50.2% (95% confidence interval [CI] = 28.2%-68.7%). There was no difference in survival (P = .67) when patients were dichotomized based upon IgG level at last follow-up (IgG ≥400 mg/dL, n = 14; and IgG <400 mg/dL, n = 9). There was no also evidence of an association between survival and: total dose (P = .58), frequency (P = .11), and number of IgG doses administered (P = .8). There was no difference in survival between patients receiving (n = 12) or not receiving (n = 11) cytomegalovirus hyperimmunoglobulin (P = .10). CONCLUSIONS Improved survival rates were not found in our IT recipients with severe HGG with immunoglobulin therapy to IgG levels of ≥400 mg/dL, even when cytomegalovirus hyperimmunoglobulin was administered.
Collapse
Affiliation(s)
- J A Poole
- Pulmonary, Critical Care, Sleep and Allergy Division, Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska
| | - F Qiu
- Biostatistics Department, University of Nebraska Medical Center, Omaha, Nebraska
| | - A C Kalil
- Transplant Infectious Diseases Program, Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska
| | - W Grant
- Transplant Surgery Division, University of Nebraska Medical Center, Omaha, Nebraska
| | - D F Mercer
- Transplant Surgery Division, University of Nebraska Medical Center, Omaha, Nebraska
| | - D F Florescu
- Transplant Infectious Diseases Program, Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Transplant Surgery Division, University of Nebraska Medical Center, Omaha, Nebraska.
| |
Collapse
|
|
44
|
Parekh R, Kazimi M, Skorupski S, Fagoaga O, Jafri S, Segovia MC. Intestine Transplantation Across a Positive Crossmatch With Preformed Donor-Specific Antibodies. Transplant Proc 2017; 48:489-91. [PMID: 27109984 DOI: 10.1016/j.transproceed.2015.10.084] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Accepted: 10/21/2015] [Indexed: 01/11/2023]
Abstract
BACKGROUND We describe our experience using a modified protocol for immunosuppression for intestine transplantation across a positive crossmatch. Patients who underwent transplantation in 2013 were evaluated over a 12-month period for rejection and infectious events with comparison to procedure-matched controls on our standard protocol of immunosuppression. PATIENTS AND METHODS We used a modified protocol for intestine and multivisceral transplantation for patients with a positive flow crossmatch. In addition to our standard protocol, patients with positive crossmatch were given rituximab and intravenous immunoglobulin (IVIg) preoperatively. DSA was sent for clinical evaluation at monthly intervals. Patients were screened for rejection by endoscopic evaluation. RESULTS Four patients underwent transplantation within a single year across a positive crossmatch. Two received isolated intestine transplants and 2 had multivisceral transplantation (MVT). During the 12-month follow-up, 1 patients had an episode of severe acute cellular rejection, which was managed with increased immunosuppression. None of the patients had episodes of cytomegalovirus infection. One patient developed major infection and 3 patients developed minor bacterial infections. Among procedure-matched controls with negative final crossmatch on standard management (no preoperative rituximab or IVIg), 2 developed mild acute cellular rejection and 2 developed minor infections. One developed cytomegalovirus viremia with invasion to the colonic mucosa. CONCLUSIONS We report our protocol for immunosuppression for IT and MVT across a positive crossmatch. This allowed transplantation despite the presence of a positive crossmatch, with low rejection rates but potentially increased risk for major infections compared to the negative crossmatch controls on our standard protocol.
Collapse
Affiliation(s)
- R Parekh
- Department of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, Michigan
| | - M Kazimi
- Department of Transplant Surgery, Henry Ford Hospital, Detroit, Michigan
| | - S Skorupski
- Department of Pathology, Henry Ford Hospital, Detroit, Michigan
| | - O Fagoaga
- Department of Pathology, Henry Ford Hospital, Detroit, Michigan
| | - S Jafri
- Department of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, Michigan
| | - M C Segovia
- Department of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, Michigan.
| |
Collapse
|
|
45
|
Kroemer A, Cosentino C, Kaiser J, Matsumoto CS, Fishbein TM. Intestinal Transplant Inflammation: the Third Inflammatory Bowel Disease. Curr Gastroenterol Rep 2016; 18:56. [PMID: 27645751 DOI: 10.1007/s11894-016-0530-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Intestinal transplantation is the most immunologically complex of all abdominal organ transplants. Understanding the role both humoral and innate and adaptive cellular immunity play in intestinal transplantation is critical to improving outcomes and increasing indications for patients suffering from intestinal failure. Recent findings highlighting the impact of donor-specific antibodies on intestinal allografts, the role of NOD2 as a key regulator of intestinal immunity, the protective effects of innate lymphoid cells, and the role of Th17 in acute cellular rejection are reviewed here.
Collapse
Affiliation(s)
- Alexander Kroemer
- MedStar Georgetown Transplant Institute, 2PHC, Georgetown University Hospital, 3800 Reservoir Road NW, Washington, DC, 20007, USA.
| | - Christopher Cosentino
- MedStar Georgetown Transplant Institute, 2PHC, Georgetown University Hospital, 3800 Reservoir Road NW, Washington, DC, 20007, USA
| | - Jason Kaiser
- MedStar Georgetown Transplant Institute, 2PHC, Georgetown University Hospital, 3800 Reservoir Road NW, Washington, DC, 20007, USA
| | - Cal S Matsumoto
- MedStar Georgetown Transplant Institute, 2PHC, Georgetown University Hospital, 3800 Reservoir Road NW, Washington, DC, 20007, USA
| | - Thomas M Fishbein
- MedStar Georgetown Transplant Institute, 2PHC, Georgetown University Hospital, 3800 Reservoir Road NW, Washington, DC, 20007, USA
| |
Collapse
|
|
46
|
Wu GS. Updates on antibody-mediated rejection in intestinal transplantation. World J Transplant 2016; 6:564-572. [PMID: 27683635 PMCID: PMC5036126 DOI: 10.5500/wjt.v6.i3.564] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 06/26/2016] [Accepted: 08/18/2016] [Indexed: 02/05/2023] Open
Abstract
Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation.
Collapse
|
|
47
|
Lipoxin A4 Preconditioning Attenuates Intestinal Ischemia Reperfusion Injury through Keap1/Nrf2 Pathway in a Lipoxin A4 Receptor Independent Manner. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:9303606. [PMID: 27375835 PMCID: PMC4914733 DOI: 10.1155/2016/9303606] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 03/24/2016] [Accepted: 04/04/2016] [Indexed: 02/07/2023]
Abstract
Oxidative stress plays a critical role in the pathogenesis of intestinal ischemia reperfusion (IIR) injury. Enhancement in endogenous Lipoxin A4 (LXA4), a potent antioxidant and mediator, is associated with attenuation of IIR. However, the effects of LXA4 on IIR injury and the potential mechanisms are unknown. In a rat IIR (ischemia 45 minutes and subsequent reperfusion 6 hours) model, IIR caused intestinal injury, evidenced by increased serum diamine oxidase, D-lactic acid, intestinal-type fatty acid-binding protein, and the oxidative stress marker 15-F2t-Isoprostane. LXA4 treatment significantly attenuated IIR injury by reducing mucosal 15-F2t-Isoprostane and elevating endogenous antioxidant superoxide dismutase activity, accompanied with Keap1/Nrf2 pathway activation. Meanwhile, LXA4 receptor antagonist Boc-2 reversed the protective effects of LXA4 on intestinal injury but failed to affect the oxidative stress and the related Nrf2 pathway. Furthermore, Nrf2 antagonist brusatol reversed the antioxidant effects conferred by LXA4 and led to exacerbation of intestinal epithelium cells oxidative stress and apoptosis, finally resulting in a decrease of survival rate of rat. Meanwhile, LXA4 pretreatment upregulated nuclear Nrf2 level and reduced hypoxia/reoxygenation-induced IEC-6 cell damage and Nrf2 siRNA reversed this protective effect of LXA4 in vitro. In conclusion, these findings suggest that LXA4 ameliorates IIR injury by activating Keap1/Nrf2 pathway in a LXA4 receptor independent manner.
Collapse
|
|
48
|
Abstract
Intestinal transplantation (IT) is the least common form of organ transplantation; however, it has shown exceptional growth and improvement in graft survival rates over the past two decades mainly due to better outcomes achieved during the first year of transplantation (76 % at 1 year), due to improvement in surgical techniques and the development of better immunosupressive therapies as we understand more about the relationship between the recipient and host immune system. There are still ongoing issues with chronic rejection and long-term survival. Intestinal transplantation is still an acceptable therapy for patients with intestinal failure (IF), but it is generally reserved for patients who develop severe and life-threatening complications despite standard therapies, or those who are not able to maintain a good quality of life. The purpose of this review is to describe the current status, indications, outcomes and advances in the field of intestinal transplantation.
Collapse
|
|
49
|
Abstract
Intestinal failure (IF) is a state in which the nutritional demands are not met by the gastrointestinal absorptive surface. A majority of IF cases are associated with short-bowel syndrome, which is a result of malabsorption after significant intestinal resection for numerous reasons, some of which include Crohn's disease, vascular thrombosis, and radiation enteritis. IF can also be caused by obstruction, dysmotility, and congenital defects. Recognition and management of IF can be challenging, given the complex nature of this condition. This review discusses the management of IF with a focus on intestinal rehabilitation, parenteral nutrition, and transplantation.
Collapse
|
|
50
|
|