Publications by authors named "Kareem Abu-Elmagd"

125 Publications

The liver and intestinal allocation policy: Decades of disparity calling for action.

Am J Transplant 2021 Nov 27. Epub 2021 Nov 27.

Center for Gut Rehabilitation and Transplantation, Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16897DOI Listing
November 2021

Blockade or deficiency of PD-L1 expression in intestinal allograft accelerates graft tissue injury in mice.

Am J Transplant 2021 Oct 22. Epub 2021 Oct 22.

Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.

The importance of PD-1/PD-L1 interaction to alloimmune response is unknown in intestinal transplantation. We tested whether PD-L1 regulates allograft tissue injury in murine intestinal transplantation. PD-L1 expression was observed on the endothelium and immune cells in the intestinal allograft. Monoclonal antibody treatment against PD-L1 led to accelerated allograft tissue damage, characterized by severe cellular infiltrations, massive destruction of villi, and increased crypt apoptosis in the graft. Interestingly, PD-L1 allografts were more severely rejected than wild-type allografts, but the presence or absence of PD-L1 in recipients did not affect the degree of allograft injury. PD-L1 allografts showed increased infiltrating Ly6G and CD11b cells in lamina propria on day 4, whereas the degree of CD4 or CD8 T cell infiltration was comparable to wild-type allografts. Gene expression analysis revealed that PD-L1 allografts had increased mRNA expressions of Cxcr2, S100a8/9, Nox1, IL1rL1, IL1r2, and Nos2 in the lamina propria cells on day 4. Taken together, study results suggest that PD-L1 expression in the intestinal allograft, but not in the recipient, plays a critical role in mitigating allograft tissue damage in the early phase after transplantation. The PD-1/PD-L1 interaction may contribute to immune regulation of the intestinal allograft via the innate immune system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16873DOI Listing
October 2021

Five Hundred Patients With Gut Malrotation: Thirty Years of Experience With the Introduction of a New Surgical Procedure.

Ann Surg 2021 10;274(4):581-596

Cleveland Clinic Foundation, Cleveland, Ohio.

Objectives: Define clinical spectrum and long-term outcomes of gut malrotation. With new insights, an innovative procedure was introduced and predictive models were established.

Methods: Over 30-years, 500 patients were managed at 2 institutions. Of these, 274 (55%) were children at time of diagnosis. At referral, 204 (41%) patients suffered midgut-loss and the remaining 296 (59%) had intact gut with a wide range of digestive symptoms. With midgut-loss, 189 (93%) patients underwent surgery with gut transplantation in 174 (92%) including 16 of 31 (16%) who had autologous gut reconstruction. Ladd's procedure was documented in 192 (38%) patients with recurrent or de novo volvulus in 41 (21%). For 80 patients with disabling gastrointestinal symptoms, gut malrotation correction (GMC) surgery "Kareem's procedure" was offered with completion of the 270° embryonic counterclockwise-rotation, reversal of vascular-inversion, and fixation of mesenteric-attachments. Concomitant colonic dysmotility was observed in 25 (31%) patients.

Results: The cumulative risk of midgut-loss increased with volvulus, prematurity, gastroschisis, and intestinal atresia whereas reduced with Ladd's and increasing age. Transplant cumulative survival was 63% at 10-years and 54% at 20-years with best outcome among infants and liver-containing allografts. Autologous gut reconstruction achieved 78% and GMC had 100% 10-year survival. Ladd's was associated with 21% recurrent/de novo volvulus and worsening (P > 0.05) of the preoperative National Institute of Health patient-reported outcomes measurement information system gastrointestinal symptom scales. GMC significantly (P ≤ 0.001) improved all of the symptomatology domains with no technical complications or development of volvulus. GMC improved quality of life with restored nutritional autonomy (P < 0.0001) and daily activities (P < 0.0001).

Conclusions: Gut malrotation is a clinicopathologic syndrome affecting all ages. The introduced herein definitive correction procedure is safe, effective, and easy to perform. Accordingly, the current standard of care practice should be redefined in this orphan population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000005072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428856PMC
October 2021

Disease recurrence after gut transplantation.

Curr Opin Organ Transplant 2021 04;26(2):207-219

Cleveland Clinic, Center for Gut Rehabilitation and Transplantation, Cleveland, Ohio, USA.

Purpose Of Review: Despite three decades of clinical experience, this article is the first to comprehensively address disease recurrence after gut transplantation. Pertinent scientific literature is reviewed and management strategies are discussed with new insights into advances in gut pathobiology and human genetics.

Recent Findings: With growing experience and new perspectives in the field of gut transplantation, the topic of disease recurrence continues to evolve. The clinicopathologic spectrum and diagnostic criteria are better defined in milieu of the nature of the primary disease. In addition to neoplastic disorders, disease recurrence is suspected in patients with pretransplant Crohn's disease, gut dysmotility, hypercoagulability and metabolic syndrome. There has also been an increased awareness of the potential de-novo development of various disorders in the transplanted organs. For conventionally unresectable gastrointestinal and abdominal malignancies, ex-vivo excision and autotransplantation are advocated, particularly for the nonallotransplant candidates.

Summary: Similar to other solid organ and cell transplantations, disease recurrence has been suspected following gut transplantation. Despite current lack of conclusive diagnostic criteria, recurrence of certain mucosal and neuromuscular disorders has been recently described in a large single-centre series with an overall incidence of 7%. Disease recurrence was also observed in recipients with pretransplant hypercoagulability and morbid obesity with respective incidences of 4 and 24%. As expected, tumour recurrence is largely determined by type, extent and biologic behaviour of the primary neoplasm. With the exception of high-grade aggressive malignancy, disease recurrence is still of academic interest with no significant impact on overall short and long-term outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOT.0000000000000856DOI Listing
April 2021

Recurrence of Crohn's Disease After Small Bowel Transplantation: Fact or Fiction.

Inflamm Bowel Dis 2020 01;26(1):21-23

Department of Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Small bowel transplant is an acceptable procedure for intractable Crohn's disease (CD). Some case reports and small series describe the apparent recurrence of CD in the transplanted bowel. This commentary discusses evidence in favor of and against this alleged recurrence and argues that a molecular characterization is needed to prove or disprove that inflammation emerging in the transplanted bowel is a true recurrence of the original CD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ibd/izz248DOI Listing
January 2020

Management of Five Hundred Patients With Gut Failure at a Single Center: Surgical Innovation Versus Transplantation With a Novel Predictive Model.

Ann Surg 2019 10;270(4):656-674

Cleveland Clinic Foundation, Cleveland, OH.

Objective(s): To define the evolving role of integrative surgical management including transplantation for patients gut failure (GF).

Methods: A total of 500 patients with total parenteral nutrition-dependent catastrophic and chronic GF were referred for surgical intervention particularly transplantation and comprised the study population. With a mean age of 45 ± 17 years, 477 (95%) were adults and 23 (5%) were children. Management strategy was guided by clinical status, splanchnic organ functions, anatomy of residual gut, and cause of GF. Surgery was performed in 462 (92%) patients and 38 (8%) continued medical treatment. Definitive autologous gut reconstruction (AGR) was achievable in 378 (82%), primary transplant in 42 (9%), and AGR followed by transplant in 42 (9%). The 84 transplant recipients received 94 allografts; 67 (71%) liver-free and 27 (29%) liver-contained. The 420 AGR patients received a total of 790 reconstructive and remodeling procedures including primary reconstruction, interposition alimentary-conduits, intestinal/colonic lengthening, and reductive/decompressive surgery. Glucagon-like peptide-2 was used in 17 patients.

Results: Overall patient survival was 86% at 1-year and 68% at 5-years with restored nutritional autonomy (RNA) in 63% and 78%, respectively. Surgery achieved a 5-year survival of 70% with 82% RNA. AGR achieved better long-term survival and transplantation better (P = 0.03) re-established nutritional autonomy. Both AGR and transplant were cost effective and quality of life better improved after AGR. A model to predict RNA after AGR was developed computing anatomy of reconstructed gut, total parenteral nutrition requirements, cause of GF, and serum bilirubin.

Conclusions: Surgical integration is an effective management strategy for GF. Further progress is foreseen with the herein-described novel techniques and established RNA predictive model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003523DOI Listing
October 2019

Twenty Years of Gut Transplantation for Chronic Intestinal Pseudo-obstruction: Technical Innovation, Long-term Outcome, Quality of Life, and Disease Recurrence.

Ann Surg 2021 02;273(2):325-333

Cleveland Clinic Foundation, Cleveland, OH.

Objective: To define long-term outcome, predictors of survival, and risk of disease recurrence after gut transplantation (GT) in patients with chronic intestinal pseudo-obstruction (CIPO).

Background: GT has been increasingly used to rescue patients with CIPO with end-stage disease and home parenteral nutrition (HPN)-associated complications. However, long-term outcome including quality of life and risk of disease recurrence has yet to be fully defined.

Methods: Fifty-five patients with CIPO, 23 (42%) children and 32 (58%) adults, underwent GT and were prospectively studied. All patients suffered gut failure, received HPN, and experienced life-threatening complications. The 55 patients received 62 allografts; 43 (67%) liver-free and 19 (33%) liver-contained with 7 (13%) retransplants. Hindgut reconstruction was adopted in 1993 and preservation of native spleen was introduced in 1999. Immunosuppression was tacrolimus-based with antilymphocyte recipient pretreatment in 41 (75%).

Results: Patient survival was 89% at 1 year and 69% at 5 years with respective graft survival of 87% and 56%. Retransplantation was successful in 86%. Adults experienced better patient (P = 0.23) and graft (P = 0.08) survival with lower incidence of post-transplant lymphoproliferative disorder (P = 0.09) and graft versus host disease (P = 0.002). Antilymphocyte pretreatment improved overall patient (P = 0.005) and graft (P = 0.069) survival. The initially restored nutritional autonomy was sustainable in 23 (70%) of 33 long-term survivors with improved quality of life. The remaining 10 recipients required reinstitution of HPN due to allograft enterectomy (n = 3) or gut dysfunction (n = 7). Disease recurrence was highly suspected in 4 (7%) recipients.

Conclusions: GT is life-saving for patients with end-stage CIPO and HPN-associated complications. Long-term survival is achievable with better quality of life and low risk of disease recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003265DOI Listing
February 2021

Chronic rejection after intestinal transplantation: A systematic review of experimental models.

Transplant Rev (Orlando) 2019 07 11;33(3):173-181. Epub 2019 Apr 11.

Department of Surgery, University Hospital of Bonn, Bonn, Germany. Electronic address:

Intestinal transplantation (ITX) constitutes a salvage treatment for irreversible intestinal failure and failure of parenteral nutrition. Chronic rejection (CR) remains the key obstacle for long-term intestinal graft survival but the pathomechanisms are incompletely understood. This study systematically reviews experimental models addressing CR after ITX in order to summarize current knowledge on CR pathogenesis and identify promising experimental strategies. A systematic literature search was conducted in line with the PRISMA guidelines, and 68 out of 677 articles qualified for the final analysis. The average methodological quality of the studies was suboptimal with 7 out of 11 points as assessed by a modified Oxford Centre for Evidence-Based Medicine score. Histology of the chronically rejected graft was almost universally integrated as outcome parameter but we found significant heterogeneity in utilized transplant techniques, organ preservation, immunosuppression and time points of CR-assessment. Several studies identified cellular and humoral immunologic mechanisms in chronic intestinal rejection. Yet, neither preventive nor therapeutic strategies against CR have been successfully introduced into human intestinal transplantation highlighting the persistent need for optimized experimental models. In this review, we aim to improve the translational value of forthcoming investigations on CR by discussing the experimental status quo and potential innovative approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trre.2019.04.001DOI Listing
July 2019

Evidence-Based Strategies and Recommendations for Preservation of Central Venous Access in Children.

JPEN J Parenter Enteral Nutr 2019 07 21;43(5):591-614. Epub 2019 Apr 21.

VANGUARD, Venous Access (VANGUARD) Task Force, Society of Interventional Radiology (SIR), Pittsburgh, Pennsylvania, USA.

Children with chronic illness often require prolonged or repeated venous access. They remain at high risk for venous catheter-related complications (high-risk patients), which largely derive from elective decisions during catheter insertion and continuing care. These complications result in progressive loss of the venous capital (patent and compliant venous pathways) necessary for delivery of life-preserving therapies. A nonstandardized, episodic, isolated approach to venous care in these high-need, high-cost patients is too often the norm, imposing a disproportionate burden on affected persons and escalating costs. This state-of-the-art review identifies known failure points in the current systems of venous care, details the elements of an individualized plan of care, and emphasizes a patient-centered, multidisciplinary, collaborative, and evidence-based approach to care in these vulnerable populations. These guidelines are intended to enable every practitioner in every practice to deliver better care and better outcomes to these patients through awareness of critical issues, anticipatory attention to meaningful components of care, and appropriate consultation or referral when necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jpen.1591DOI Listing
July 2019

Composite and Multivisceral Transplantation: Nomenclature, Surgical Techniques, Current Practice, and Long-term Outcome.

Surg Clin North Am 2019 Feb;99(1):129-151

Center for Gut Rehabilitation and Transplantation, Cleveland Clinic, 9500 Euclid Avenue, Desk A100, Cleveland, OH 44195, USA; Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Desk A100, Cleveland, OH 44195, USA. Electronic address:

The successful development of multivisceral and composite visceral transplantation is among the milestones in the recent history of human organ transplantation. All types of gastrointestinal transplantation have evolved to be the standard of care for patients with gut failure and complex abdominal pathologic conditions. The outcome has markedly improved over the last 3 decades owing to technical innovation, novel immunosuppression, and better postoperative care. Recent data documented significant improvement in the long-term therapeutic indices of all types of visceral transplantation close to that achieved with thoracic and solid abdominal organs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suc.2018.09.010DOI Listing
February 2019

Composite and Multivisceral Transplantation: Nomenclature, Surgical Techniques, Current Practice, and Long-term Outcome.

Gastroenterol Clin North Am 2018 Jun;47(2):393-415

Center for Gut Rehabilitation and Transplantation, Cleveland Clinic, 9500 Euclid Avenue, Desk A100, Cleveland, OH 44195, USA; Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Desk A100, Cleveland, OH 44195, USA. Electronic address:

The successful development of multivisceral and composite visceral transplantation is among the milestones in the recent history of human organ transplantation. All types of gastrointestinal transplantation have evolved to be the standard of care for patients with gut failure and complex abdominal pathologic conditions. The outcome has markedly improved over the last 3 decades owing to technical innovation, novel immunosuppression, and better postoperative care. Recent data documented significant improvement in the long-term therapeutic indices of all types of visceral transplantation close to that achieved with thoracic and solid abdominal organs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gtc.2018.01.013DOI Listing
June 2018

Total pancreaticoduodenectomy with autologous islet transplantation 14 years after liver-contained composite visceral transplantation.

Am J Transplant 2018 08 14;18(8):2068-2074. Epub 2018 May 14.

Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.

Chronic pancreatitis (CP) is a severely disabling disorder with potential detrimental effects on quality of life, gut function, and glucose homeostasis. Disease progression often results in irreversible morphological and functional abnormalities with development of chronic pain, mechanical obstruction, and pancreatic insufficiency. Along with comprehensive medical management, the concept of total pancreatectomy and islet autotransplantation (TP-AIT) was introduced 40 years ago for patients with intractable pain and preserved beta-cell function. With anticipated technical difficulties, total excision of the inflamed-disfigured gland is expected to alleviate the incapacitating visceral pain and correct other associated abdominal pathology. With retrieval of sufficient islet-cell mass, the autologous transplant procedure has the potential to maintain an euglycemic state without exogenous insulin requirement. The reported herein case of CP-induced recalcitrant pain and foregut obstruction is exceptional because of the technical challenges in performing native pancreaticoduodenectomy in close proximity to the composite visceral allograft with complex vascular and gut reconstructions. Equally novel is transplanting the auto-islets in the liver-contained visceral allograft. Despite intravenous nutrition shortly after birth, liver transplantation at age 13, retransplantation with liver-contained visceral allograft at age 17 and TP-AIT at age 31, the 38-year-old recipient is currently pain free with full nutritional autonomy and normal glucose homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.14880DOI Listing
August 2018

Imaging of Intestinal and Multivisceral Transplantation.

Radiographics 2018 Mar-Apr;38(2):413-432

From the Departments of Radiology (M.A.R., N.B.A., A.A.B., A.K.D.) and Surgery (R.J.C.), University of Pittsburgh Medical Center, 200 Lothrop St, Radiology Suite 200, East Wing E2051B, Pittsburgh, PA 15213; and Department of Surgery, Cleveland Clinic Foundation, Cleveland, Ohio (K.M.A., G.C.).

Intestinal transplantation has evolved from its experimental origins in the mid-20th century to its status today as an established treatment option for patients with end-stage intestinal failure who cannot be sustained with total parenteral nutrition. The most common source of intestinal failure in both adults and children is short-bowel syndrome, but a host of other disease processes can lead to this common end-point. The development of intestinal transplantation has presented multiple hurdles for the transplant community, including technical challenges, immunologic pitfalls, and infectious complications. Despite these hurdles, the success rate has climbed over the past decades owing to achievements that include improved surgical techniques, new immunosuppressive regimens, and more effective strategies for posttransplant surveillance and management. Nearly 2800 intestinal transplants have been performed worldwide, and current patient and graft survival rates are now comparable to those of other types of solid organ transplantations. As their population continues to increase, it will be increasingly likely that intestinal-transplant patients will seek imaging at sites other than transplant centers. Therefore, it is important that diagnostic and interventional radiologists be familiar with the procedure, its common variations, and the spectrum of postoperative complications. In this article, the authors provide an overview of intestinal transplantation, including the indications, variations, expected postoperative anatomy, and range of potential complications. RSNA, 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/rg.2018170086DOI Listing
August 2018

Myeloid-derived suppressor cells increase and inhibit donor-reactive T cell responses to graft intestinal epithelium in intestinal transplant patients.

Am J Transplant 2018 10 17;18(10):2544-2558. Epub 2018 Apr 17.

Transplant Center, Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.

Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal and multivisceral transplant (ITx) recipient survival. We investigated the role of myeloid-derived suppressor cells (MDSCs) in ITx. We identified MDSCs as CD33 CD11b lineage(CD3/CD56/CD19) HLA-DR cells with 3 subsets, CD14 CD15 (e-MDSCs), CD14 CD15 (M-MDSCs), and CD14 CD15 (PMN-MDSCs), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs after ITx; among MDSC subsets, M-MDSC numbers were maintained at a high level after 2 months post ITx. The MDSC numbers decreased in ITx recipients with ACR. MDSC numbers were positively correlated with serum interleukin (IL)-6 levels and the glucocorticoid administration index. IL-6 and methylprednisolone enhanced the differentiation of bone marrow cells to MDSCs in vitro. M-MDSCs and e-MDSCs expressed CCR1, -2, and -3; e-MDSCs and PMN-MDSCs expressed CXCR2; and intestinal grafts expressed the corresponding chemokine ligands after ITx. Of note, the percentage of MDSCs among intestinal mucosal CD45 cells increased after ITx. A novel in vitro assay demonstrated that MDSCs suppressed donor-reactive T cell-mediated destruction of donor intestinal epithelial organoids. Taken together, our results suggest that MDSCs accumulate in the recipient PBMCs and the grafted intestinal mucosa in ITx, and may regulate ACR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.14718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127002PMC
October 2018

Chronic Central Venous Access: From Research Consensus Panel to National Multistakeholder Initiative.

J Vasc Interv Radiol 2018 04 15;29(4):461-469. Epub 2018 Feb 15.

Division of Vascular and Interventional Radiology, Department of Radiology, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvir.2017.12.009DOI Listing
April 2018

Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion.

Liver Transpl 2018 02;24(2):233-245

Transplantation Center, Cleveland Clinic, Cleveland, OH.

Normothermic machine perfusion (NMP) is an emerging technology to preserve liver allografts more effectively than cold storage (CS). However, little is known about the effect of NMP on steatosis and the markers indicative of hepatic quality during NMP. To address these points, we perfused 10 discarded human livers with oxygenated NMP for 24 hours after 4-6 hours of CS. All livers had a variable degree of steatosis at baseline. The perfusate consisted of packed red blood cells and fresh frozen plasma. Perfusate analysis showed an increase in triglyceride levels from the 1st hour (median, 127 mg/dL; interquartile range [IQR], 95-149 mg/dL) to 24th hour of perfusion (median, 203 mg/dL; IQR, 171-304 mg/dL; P = 0.004), but tissue steatosis did not decrease. Five livers produced a significant amount of bile (≥5 mL/hour) consistently throughout 24 hours of NMP. Lactate in the perfusate cleared to <3 mmol/L in most livers within 4-8 hours of NMP, which was independent of bile production rate. This is the first study to characterize the lipid profile and functional assessment of discarded human livers at 24 hours of NMP. Liver Transplantation 24 233-245 2018 AASLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.24972DOI Listing
February 2018

Metabolic Consequences of Restorative Surgery After Gastric Bypass.

Diabetes Care 2017 04 7;40(4):e42-e43. Epub 2017 Feb 7.

Department of General Surgery, Cleveland Clinic, Cleveland, OH.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc16-2561DOI Listing
April 2017

Current status of intestinal and multivisceral transplantation.

Gastroenterol Rep (Oxf) 2017 02 26;5(1):20-28. Epub 2017 Jan 26.

Center for Gut Rehabilitation and Transplantation, the Cleveland Clinic Foundation, Cleveland, OH, USA

Clinical-nutritional autonomy is the ultimate goal of patients with intestinal failure (IF). Traditionally, patients with IF have been relegated to lifelong parenteral nutrition (PN) once surgical and medical rehabilitation attempts at intestinal adaptation have failed. Over the past two decades, however, outcome improvements in intestinal transplantation have added another dimension to the therapeutic armamentarium in the field of gut rehabilitation. This has become possible through relentless efforts in the standardization of surgical techniques, advancements in immunosuppressive therapies and induction protocols and improvement in postoperative patient care. Four types of intestinal transplants include isolated small bowel transplant, liver-small bowel transplant, multivisceral transplant and modified multivisceral transplant. Current guidelines restrict intestinal transplantation to patients who have had significant complications from PN including liver failure and repeated infections. From an experimental stage to the currently established therapeutic modality for patients with advanced IF, outcome improvements have also been possible due to the introduction of tacrolimus in the early 1990s. Studies have shown that intestinal transplant is cost-effective within 1-3 years of graft survival compared with PN. Improved survival and quality of life as well as resumption of an oral diet should enable intestinal transplantation to be an important option for patients with IF in addition to continued rehabilitation. Future research should focus on detecting biomarkers of early rejection, enhanced immunosuppression protocols, improved postoperative care and early referral to transplant centers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gastro/gow045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444259PMC
February 2017

Recombinant HLA-G as Tolerogenic Immunomodulant in Experimental Small Bowel Transplantation.

PLoS One 2016 12;11(7):e0158907. Epub 2016 Jul 12.

Department of Surgery, University Hospital of Bonn, Bonn, Germany.

The non-classical MHC I paralogue HLA-G is expressed by cytotrophoblast cells and implicated with fetomaternal tolerance by downregulating the maternal adaptive and innate immune response against the fetus. HLA-G expression correlates with favorable graft outcome in humans and recently promising immunosuppressive effects of therapeutic HLA-G in experimental transplantation (skin allograft acceptance) were shown. Consequently, we examined this novel therapeutic approach in solid organ transplantation. In this study, therapeutic recombinant HLA-G5 was evaluated for the first time in a solid organ model of acute rejection (ACR) after orthotopic intestinal transplantation (ITX). Allogenic ITX was performed in rats (Brown Norway to Lewis) with and without HLA-G treatment. It was found that HLA-G treatment significantly reduced histologically proven ACR at both an early and late postoperative timepoint (POD 4/7), concomitant to a functionally preserved graft contractility at POD 7. Interestingly, graft infiltration by myeloperoxidase+ cells was significantly reduced at POD7 by HLA-G treatment. Moreover, HLA-G treatment showed an effect on the allogenic T-cell immune response as assessed by flow cytometry: The influx of recipient-derived CD8+ T-cells into the graft mesenteric lymphnodes at POD7 was significantly reduced while CD4+ populations were not affected. As a potential mechanism of action, an induction of T-reg populations in the mesenteric lymphnodes was postulated, but flow cytometric analysis of classical CD4+/CD25+/FoxP3+Treg-cells showed no significant alteration by HLA-G treatment. The novel therapeutic approach using recombinant HLA-G5 reported herein demonstrates a significant immunosuppressive effect in this model of allogenic experimental intestinal transplantation. This effect may be mediated via inhibition of recipient-derived CD8+ T-cell populations either directly or by induction of non-classical Treg populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158907PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942037PMC
July 2017

Management of Crohn's Disease in the New Era of Gut Rehabilitation and Intestinal Transplantation.

Inflamm Bowel Dis 2016 07;22(7):1763-76

*Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, Ohio; †Department of Gastroenterology & Hepatology, Cleveland Clinic, Cleveland, Ohio; and ‡Center for Gut Rehabilitation and Transplantation, Transplant Center, Cleveland Clinic, Cleveland, Ohio.

Despite recent therapeutic advances, patients with Crohn's disease (CD) continue to experience high recurrence with cumulative structural damage and ultimate loss of nutritional autonomy. With short bowel syndrome, strictures, and enteric fistulae being the underlying pathology, CD is the second common indication for home parenteral nutrition (HPN). With development of intestinal failure, nutritional management including HPN is required as a rescue therapy. Unfortunately, some patients do not escape the HPN-associated complications. Therefore, the concept of gut rehabilitation has evolved as part of the algorithmic management of these patients, with transplantation being the ultimate life-saving therapy. With type 2 intestinal failure, comprehensive rehabilitative measures including nutritional care, pharmacologic manipulation, autologous reconstruction, and bowel lengthening is often successful, particularly in patients with quiescent disease. With type 3 intestinal failure, transplantation is the only life-saving treatment for patients with HPN failure and intractable disease. With CD being the second common indication for transplantation in adults, survival outcome continues to improve because of surgical innovation, novel immunosuppression, and better postoperative care. Despite being a rescue therapy, the procedure has achieved survival rates similar to other solid organs, and comparable to those who continue to receive HPN therapy. With similar technical, immunologic, and infectious complications, survival is similar in the CD and non-CD recipients. Full nutritional autonomy is achievable in most survivors with better quality of life and long-term cost-effectiveness. CD recurrence is rare with no impact on graft function. Further progress is anticipated with new insights into the pathogenesis of CD and mechanisms of transplant tolerance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MIB.0000000000000792DOI Listing
July 2016

Autologous Reconstruction and Visceral Transplantation for Management of Patients With Gut Failure After Bariatric Surgery: 20 Years of Experience.

Ann Surg 2015 Oct;262(4):586-601

*Cleveland Clinic Foundation, Cleveland, OH †Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA ‡East Carolina University, Greenville, NC §Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Objective: Bariatric surgery (BS) is currently the most effective treatment for severe obesity. However, these weight loss procedures may result in the development of gut failure (GF) with the need for total parenteral nutrition (TPN). This retrospective study is the first to address the anatomic and functional spectrum of BS-associated GF with innovative surgical modalities to restore gut function.

Methods: Over 2 decades, 1500 adults with GF were referred with history of BS in 142 (9%). Of these, 131 (92%) were evaluated and received multidisciplinary care. GF was due to catastrophic gut loss (Type-I, 42%), technical complications (Type-II, 33%), and dysfunctional syndromes (Type-III, 25%). Primary bariatric procedures were malabsorptive (5%), restrictive (19%), and combined (76%). TPN duration ranged from 2 to 252 months.

Results: Restorative surgery was performed in 116 (89%) patients with utilization of visceral transplantation as a rescue therapy in 23 (20%). With a total of 317 surgical procedures, 198 (62%) were autologous reconstructions; 88 (44%) foregut, 100 (51%) midgut, and 10 (5%) hindgut. An interposition alimentary conduit was used in 7 (6%) patients. Reversal of BS was indicated in 84 (72%) and intestinal lengthening was required in 10 (9%). Cumulative patient survival was 96% at 1 year, 84% at 5 years, and 72% at 15 years. Nutritional autonomy was restored in 83% of current survivors with persistence or relapse of obesity in 23%.

Conclusions: GF is a rare but serious life-threatening complication after BS. Successful outcome is achievable with comprehensive management, including reconstructive surgery and visceral transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000001440DOI Listing
October 2015

Atypical Clinical Presentation of a Newer Generation Anti-Fungal Drug-Resistant Fusarium Infection After a Modified Multi-Visceral Transplant.

Ann Transplant 2015 Sep 3;20:512-8. Epub 2015 Sep 3.

Department of Multi-Visceral Transplant, Cleveland Clinic, Cleveland, OH, USA.

BACKGROUND Fusarium spp. infections have become an emerging and lethal threat to the immunocompromised patient population, especially those with neutropenia. Recently there have been increased reports in solid organ transplant recipients. Presentation is commonly as soft tissue infections several months post-transplant. With high morbidity and mortality, efficacious antifungal therapy is essential. This remains challenging with limited data and no established clinical breakpoints defined. CASE REPORT We report on a modified multi-visceral transplant patient that developed a Fusarium infection only 7 weeks post-transplant in the native hard palate and esophagus, without any soft tissue lesions, which persisted despite aggressive combination treatment with amphotericin B lipid complex and voriconazole. CONCLUSIONS Fusarium spp. infection in solid organ transplant is a significant challenge without clear diagnostic clinical indicators of infection, or specific time of onset, in addition to possible emergence of a more aggressive drug-resistant strain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/AOT.892209DOI Listing
September 2015

Recent Advances in Intestinal and Multivisceral Transplantation.

Adv Surg 2015 ;49:31-63

Center for Gut Rehabilitation and Transplantation, Transplant Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yasu.2015.04.003DOI Listing
November 2016

Peritoneal decortication: an innovative technique for treatment of obstructive sclerosing encapsulating peritonitis.

Am Surg 2015 Apr;81(4):E143-5

Cleveland Clinic Foundation, Digestive Disease Institute, Cleveland, Ohio, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
April 2015

The concept of gut rehabilitation and the future of visceral transplantation.

Nat Rev Gastroenterol Hepatol 2015 Feb 20;12(2):108-20. Epub 2015 Jan 20.

Transplant Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

In the 1990s, the introduction of visceral transplantation fuelled interest in other innovative therapeutic modalities for gut rehabilitation. Ethanol lock and omega-3 lipid formulations were introduced to reduce the risks associated with total parenteral nutrition (TPN). Autologous surgical reconstruction and bowel lengthening have been increasingly utilized for patients with complex abdominal pathology and short-bowel syndrome. Glucagon-like peptide 2 analogue, along with growth hormone, are available to enhance gut adaptation and achieve nutritional autonomy. Intestinal transplantation continues to be limited to a rescue therapy for patients with TPN failure. Nonetheless, survival outcomes have substantially improved with advances in surgical techniques, immunosuppressive strategies and postoperative management. Furthermore, both nutritional autonomy and quality of life can be restored for more than two decades in most survivors, with social support and inclusion of the liver being favourable predictors of long-term outcome. One of the current challenges is the discovery of biomarkers to diagnose early rejection and further improve liver-free allograft survival. Currently, chronic rejection with persistence of preformed and development of de novo donor-specific antibodies is a major barrier to long-term graft function; this issue might be overcome with innovative immunological and tolerogenic strategies. This Review discusses advances in the field of gut rehabilitation, including intestinal transplantation, and highlights future challenges. With the growing interest in individualized medicine and the value of health care, a novel management algorithm is proposed to optimize patient care through an integrated multidisciplinary team approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nrgastro.2014.216DOI Listing
February 2015

Radiologic features of pancreatic and biliary complications following composite visceral transplantation.

Abdom Imaging 2015 Aug;40(6):1961-70

Division of Abdominal Imaging, Department of Radiology, UPMC Presbyterian Hospital, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15213, USA,

Small bowel transplantation is a surgical technique reserved for patients with end-stage intestinal failure. Despite its inherent technical difficulties, it has emerged as the standard of care for these patients. This article reviews the background and different surgical techniques for this procedure and then fully describes the spectrum of imaging findings of pancreatic and biliary complications, which have a prevalence of up to 17%, after this procedure based on 23-year single-center experience. The pancreaticobiliary complications encountered in our experience and discussed in this article include: ampullary stenosis, biliary cast, choledocholithiasis, bile leak, recurrent cholangitis, acute pancreatitis, chronic pancreatitis, and pancreatic duct fistula. Familiarity with the broad spectrum of PB complications and their variable manifestations will help radiologists to accurately diagnose these complications which have relatively high morbidity and mortality in these immune-compromised patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00261-014-0338-zDOI Listing
August 2015

Sanguineous normothermic machine perfusion improves hemodynamics and biliary epithelial regeneration in donation after cardiac death porcine livers.

Liver Transpl 2014 Aug 2;20(8):987-99. Epub 2014 Jul 2.

Transplant Center, Department of Surgery, Digestive Disease Institute, Cleveland Clinic Foundation.

The effects of normothermic machine perfusion (NMP) on the postreperfusion hemodynamics and extrahepatic biliary duct histology of donation after cardiac death (DCD) livers after transplantation have not been addressed thoroughly and represent the objective of this study. Ten livers (5 per group) with 60 minutes of warm ischemia were preserved via cold storage (CS) or sanguineous NMP for 10 hours, and then they were reperfused for 24 hours with whole blood in an isolated perfusion system to simulate transplantation. In our experiment, the arterial and portal vein flows were stable in the NMP group during the entire reperfusion simulation, whereas they decreased dramatically in the CS group after 16 hours of reperfusion (P < 0.05); these findings were consistent with severe parenchymal injury. Similarly, significant differences existed between the CS and NMP groups with respect to the release of hepatocellular enzymes, the volume of bile produced, and the levels of enzymes released into bile (P < 0.05). According to histology, CS livers presented with diffuse hepatocyte congestion, necrosis, intraparenchymal hemorrhaging, denudated biliary epithelium, and submucosal bile duct necrosis, whereas NMP livers showed very mild injury to the liver parenchyma and biliary architecture. Most importantly, Ki-67 staining in extrahepatic bile ducts showed biliary epithelial regeneration. In conclusion, our findings advance the knowledge of the postreperfusion events that characterize DCD livers and suggest NMP as a beneficial preservation modality that is able to improve biliary regeneration after a major ischemic event and may prevent the development of ischemic cholangiopathy in the setting of clinical transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.23906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117809PMC
August 2014

Ex vivo normothermic machine perfusion is safe, simple, and reliable: results from a large animal model.

Surg Innov 2015 Feb 2;22(1):61-9. Epub 2014 Apr 2.

Cleveland Clinic, Cleveland, OH, USA

Introduction: Normothermic machine perfusion (NMP) is an emerging preservation modality that holds the potential to prevent the injury associated with low temperature and to promote organ repair that follows ischemic cell damage. While several animal studies have showed its superiority over cold storage (CS), minimal studies in the literature have focused on safety, feasibility, and reliability of this technology, which represent key factors in its implementation into clinical practice. The aim of the present study is to report safety and performance data on NMP of DCD porcine livers.

Materials And Methods: After 60 minutes of warm ischemia time, 20 pig livers were preserved using either NMP (n = 15; physiologic perfusion temperature) or CS group (n = 5) for a preservation time of 10 hours. Livers were then tested on a transplant simulation model for 24 hours. Machine safety was assessed by measuring system failure events, the ability to monitor perfusion parameters, sterility, and vessel integrity. The ability of the machine to preserve injured organs was assessed by liver function tests, hemodynamic parameters, and histology.

Results: No system failures were recorded. Target hemodynamic parameters were easily achieved and vascular complications were not encountered. Liver function parameters as well as histology showed significant differences between the 2 groups, with NMP livers showing preserved liver function and histological architecture, while CS livers presenting postreperfusion parameters consistent with unrecoverable cell injury.

Conclusion: Our study shows that NMP is safe, reliable, and provides superior graft preservation compared to CS in our DCD porcine model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1553350614528383DOI Listing
February 2015

Sequential split liver followed by isolated intestinal transplant: the "liver-first" approach: report of a case.

Transplantation 2014 Feb;97(3):e17-9

1 Transplantation Center Department of General Surgery Cleveland Clinic Cleveland, OH 2 Department of Pharmacy Cleveland Clinic Cleveland, OH 3 Allogen Laboratories Transplantation Center Cleveland Clinic Cleveland, OH 4 Department of General Surgery Cleveland Clinic Cleveland, OH.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.TP.0000438201.61284.27DOI Listing
February 2014
-->