Publications by authors named "Panagiotis Tryphonopoulos"

30 Publications

  • Page 1 of 1

CD52-Negative NK Cells Are Abundant in the Liver and Less Susceptible to Alemtuzumab Treatment.

PLoS One 2016 25;11(8):e0161618. Epub 2016 Aug 25.

Division of Liver and Gastrointestinal Transplantation, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, United States of America.

Background: T-cell depleting strategies have become an integral part of immunosuppressive regimens in organ transplantation. Alemtuzumab is a humanized monoclonal antibody against CD52, a cell-surface antigen on several immune cells. It has been suggested that lymphocyte depletion increases the risk of serious infections. However, this has not been observed with short-term alemtuzumab treatment in an organ transplant setting. For induction therapy using alemtuzumab following liver transplantation, we found that T- and B-cell numbers declined rapidly after alemtuzumab therapy; however, the natural killer (NK) cell number was sustained. NK cells are important effectors of innate immunity. Since the effects of alemtuzumab on NK cell functions, especially those of liver NK cells, are unknown, this study aimed to investigate this in detail.

Methods: To assess the effect of alemtuzumab on NK cells, samples were obtained from 7 organ donors and examined by flow cytometry using Annexin V and propidium iodide. Phenotypical and functional differences within subsets of NK cells with different levels of CD52 expression were determined by flow cytometry and in vitro cytotoxicity assays.

Results: CD52 expression on NK cells was lower than that on other lymphocyte subsets. The liver contained a large number of CD52- NK cells compared with the peripheral blood. In vitro treatment of liver-derived NK cells with alemtuzumab did not result in cell death. In contrast, co-incubation with alemtuzumab induced cell death in peripheral blood mononuclear cells and non-NK cells in the liver. Furthermore, CD52- liver NK cells were more cytotoxic and produced more IFN-γ than CD52+ NK cells after cytokine activation.

Conclusion: The liver contains a large number of CD52- NK cells. These cells are refractory to alemtuzumab and have robust activity. These findings indicate that CD52- NK cells persist and could protect against infection after alemtuzumab-based lymphocyte depletion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161618PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999148PMC
August 2017

Abdominal transplantation for unresectable tumors in children: the zooming out principle.

Pediatr Surg Int 2016 Apr 28;32(4):337-46. Epub 2015 Dec 28.

Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

Purpose: To present our experience in abdominal transplantations to manage unresectable abdominal neoplasms in children and to describe the role of extensive surgeries in such cases.

Methods: This is a retrospective study of 22 abdominal transplantations in 21 patients for abdominal tumors over 16 years. Transplantation techniques included liver transplant (LT), multivisceral transplant (MVTx), and intestinal autotransplant (IA). Follow-up intervals ranged from 0.3 to 168 months (median 20 months).

Results: LT alone was performed in 15 patients for primary malignant (11) and benign (4) liver tumors. Pathological classification included HB hepatoblastoma (6), HCC hepatocellular cancer (3), hepatic epithelioid hemangioendothelioma HEH (1), angiosarcoma (1), benign vascular tumors (3), and adenoma (1). IA was performed in four patients for lesions involving the root of the mesentery; tumors of the head of pancreas (3) and mesenteric hemangioma (1). MVTx was performed in 2 patients for malignancies; pancreaticoblastoma (1), recurrent hepatoblastoma (1), and in one patient as a rescue procedure after IA failure. Four of the eleven patients who underwent LT for malignant liver tumor had metastatic disease at presentation. Six of them died of recurrent neoplasm (3), transplant-related complications (2), and underlying disease (1). All LT patients who had benign tumors are alive with functioning grafts. All IA patients survived and are on an oral diet, with one patient requiring TPN supplementation. One of the three patients who underwent MVTx died of metastatic disease.

Conclusions: Allo/auto transplantation for abdominal tumors is a valuable modality when conventional treatments fail or are not feasible.
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http://dx.doi.org/10.1007/s00383-015-3852-3DOI Listing
April 2016

Longterm outcomes of auxiliary partial orthotopic liver transplantation in preadolescent children with fulminant hepatic failure.

Liver Transpl 2016 Apr;22(4):485-94

Center for Liver Disease and Transplantation, New York Presbyterian-Columbia University Medical Center, New York, NY.

By preserving part of the native liver, auxiliary partial orthotopic liver transplantation (APOLT) provides the advantage of potential immunosuppression (ISP) withdrawal if the native liver recovers but has had limited acceptance, especially in the United States, due to technical complications and low rates of native liver regeneration. No previous study has evaluated APOLT specifically for preadolescent children with fulminant hepatic failure (FHF). This population might benefit especially based on greater capacity for liver regeneration. Data from 13 preadolescent children who underwent APOLT were compared to 13 matched controls who underwent orthotopic liver transplantation (OLT) for FHF from 1996 to 2013. There were no significant differences in patient demographics or survival between the 2 groups. However, all surviving OLT recipients (10/13) remain on ISP, while all but 1 surviving APOLT recipient (12/13) showed native liver regeneration, and the first 10 recipients (76.9%) are currently off ISP with 2 additional patients currently weaning. In our experience, APOLT produced excellent survival and high rates of native liver regeneration in preadolescent children with FHF. This represents the largest series to date to report such outcomes. Liberating these children from lifelong ISP without the downside of increased surgical morbidity makes APOLT an attractive alternative. In conclusion, we therefore propose that, with the availability of technical expertise and with the technical modifications above, APOLT for FHF should be strongly considered for preteenage children with FHF.
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http://dx.doi.org/10.1002/lt.24361DOI Listing
April 2016

Role of innate and acquired immune mechanisms in clinical intestinal transplant rejection.

Transplantation 2015 Jun;99(6):1273-81

1 Department of Surgery, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL. 2 Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL. 3 Jesse Brown VA Medical Center, Chicago, IL. 4 Department of Surgery, University of Miami Miller School of Medicine, Miami, FL. 5 Department of Microbiology-Immunology, University of Miami Miller School of Medicine, Miami, FL. 6 Miami VA Medical Center, Miami, FL. 7 Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, IL.

Background: Long-term outcomes of intestinal transplantation are limited by infection and rejection. To understand the underlying immune mechanisms, graft infiltrating and peripheral blood cells were analyzed using multiple ex vivo assays in intestinal transplantation recipients.

Methods: Infiltrating cells from rejected (graft enterectomy for rejection) and accepted or quiescent (stoma closure in stable transplant recipients) grafts were isolated and phenotypically characterized as to subsets and Toll-like receptor expressions as well as functionally tested for antimicrobial and antidonor immune responses. Multiparameter antidonor immunity was also assessed serially in the peripheral blood.

Results: The graft infiltrating lymphocytes were mostly of recipient origin in all patients tested. In rejecting grafts, the predominant populations were TcRαβ(+)CD3(+)CD8(+) T cells, and CD14(+) monocytes that coexpressed Toll-like receptor-2, receptor-3, receptor-4, receptor-5, and receptor-9, suggesting innate immune activation. In quiescent allografts the major cell subsets were CD13(+)CD14(-) monocytes and CD4(+)CD25(+) T cells with possible regulatory functions. Infiltrating cells from rejected but not quiescent grafts proliferated in response to enteric bacterial and donor antigens as well as killed donor targets. Serial follow-up of peripheral blood indicated donor-specific posttransplant unresponsiveness in micro-cell-mediated lympholysis (m-CML) and mixed lymphocyte reaction (MLR) in recipients with quiescent grafts, but not in recipients with multiple rejection episodes. Enzyme-Linked ImmunoSpot assays yielded parallel results: granzyme-B with micro-cell-mediated lympholysis and interferon-γ with MLR tests.

Conclusion: These results were consistent with the notion that rejection was associated with innate and acquired antimicrobial and antidonor immune reactivity and that patients with stable grafts were free from these deleterious effects.
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http://dx.doi.org/10.1097/TP.0000000000000491DOI Listing
June 2015

Clinical significance of intragraft miR-122 and -155 expression after liver transplantation.

Hepatol Res 2015 Aug 17;45(8):898-905. Epub 2014 Nov 17.

Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

Aim: Recurrent hepatitis C (RHC) and acute cellular rejection (AR) remain critical problems following liver transplantation (LT) in hepatitis C virus (HCV) positive recipients because of the similar clinical features. Discrimination between these conditions can be problematic, and adjunctive biomarkers would be useful to discriminate these processes. The aim of our study was to investigate the possibility of the intragraft miR-122 and -155 expression as new biomarkers after LT.

Methods: A total of 29 HCV positive recipients were enrolled in this study. Intragraft expressions of miR-122 and -155 were studied between RHC predominant (n = 17) and AR predominant cases (n = 12) using quantitative reverse transcription polymerase chain reaction. Furthermore, we investigated the correlations between these expression levels and clinical serum parameters.

Results: Intragraft miR-122 expression had a good correlation with serum alkaline phosphatase (P = 0.02), but it was not correlated with the serum HCV viral load. The expression levels of miR-122 in the AR group were significantly higher than those in the RHC group (P = 0.0006) and, inversely, the expression levels of miR-155 in the AR group were significantly lower than those in the RHC group (P = 0.01).

Conclusion: Our study emphasizes a useful pattern of miR-122 and -155 as ancillary markers to discriminate AR predominant cases from RHC in HCV positive patients after LT.
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http://dx.doi.org/10.1111/hepr.12424DOI Listing
August 2015

Allogeneic uterus transplantation in baboons: surgical technique and challenges to long-term graft survival.

Transplantation 2014 Sep;98(5):e51-6

1 Division of Liver and Intestinal Transplantation Department of Surgery University of Miami School of Medicine Miami, FL 2 Department of Surgery Cleveland Clinic Weston, FL 3 Department of Obstetrics and Gynecology Sahlgrenska Academy University of Gothenburg Göteborg, Sweden 4 The Mannheimer Foundation, Inc. Homestead, FL 5 Department of Pathology Sahlgrenska Academy University of Gothenburg Göteborg, Sweden 6 Department of Anesthesia and Intensive Care Sahlgrenska Academy University of Gothenburg Göteborg, Sweden 7 Department of Gynecology and Obstetrics La Fe University Hospital University of Valencia Valencia, Spain 8 Department of Pathology Cleveland Clinic Weston, FL 9 Department of Gynecology Cleveland Clinic Weston, FL 10 Department of Gynecology Cleveland Clinic Weston, FL 11 Sahlgrenska Transplant Institute, Department of Transplantation, Sahlgrenska Academy University of Gothenburg Göteborg, Sweden.

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http://dx.doi.org/10.1097/TP.0000000000000322DOI Listing
September 2014

Mannose binding lectin (mbl2) haplotype frequencies in solid organ transplant patients and correlation with MBL protein levels--evaluation of complement-mediated effector pathway deficiency.

Transpl Immunol 2013 Mar 22;28(2-3):73-80. Epub 2013 Feb 22.

Department of Experimental Pathology, University of Texas Medical Branch, Galveston, TX, United States.

Mannose-binding lectin (MBL) is a protein critical in activating complement. Patients with wild-type and variant mbl2 genotypes have high or low concentrations of MBL protein, which is known to increase susceptibility to transplant rejection or infection, respectively. Our objective was to determine mbl2 genotype frequencies in future solid organ transplant recipients in order to optimize their induction and maintenance immunosuppressive therapies, and to provide MBL reference data for this unique population. We genotyped 1687 patients, and concurrently measured protein in 807 of them, during 2010-2011. Frequencies of the structural allele SNPs in our population were similar to those of other studied populations; however, Black patients with the same intermediate and deficient mbl2 genotypes as Caucasians produced significantly lower levels of MBL protein; therefore, within this population more genotypes should be considered MBL-deficient. Overall, the most critical parameter in determining serum MBL protein concentration was genotype, which was independent of other factors including ethnicity, gender, or diseased native organ type.
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http://dx.doi.org/10.1016/j.trim.2013.02.002DOI Listing
March 2013

Tregs expanded in vivo by TNFRSF25 agonists promote cardiac allograft survival.

Transplantation 2012 Sep;94(6):569-74

Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.

Background: Thymic-derived Foxp3(+)CD4(+) regulatory T cells (Tregs)-also called natural Tregs-are critical for the induction and maintenance of transplantation tolerance. Using an agonistic tumor necrosis factor-receptor super family (TNFRSF) 25 antibody, clone 4C12, we showed that TNFRSF25 is a powerful regulator of Treg proliferation-mediating expansion of natural Tregs in vivo. In the present study, we investigate the role of Tregs expanded in vivo by TNFRSF25 on cardiac allograft survival in a mouse model of fully major histocompatibility complex-mismatched ectopic heart transplants.

Methods: C57BL/6 mice were treated with 20 μg of TNFRSF25 agonist 4C12 4 days before heterotopic allogeneic heart transplantation. The survival of the graft was monitored daily by abdominal palpation until the cessation of cardiac contraction. The severity of immune rejection was evaluated by histopathology. Infiltration of inflammatory cells and Tregs into the graft were characterized by flow cytometry. The expression of cytokines and other regulatory proteins was measured by quantitative real-time polymerase chain reaction.

Results: Treatment with 4C12 resulted in expansion of Tregs to 30%-35% of CD4(+) cells and was associated with a significant prolongation of median graft survival from 8 days to 17 days (P=0.0049). On day 7 after transplantation, the time point when controls reject the graft, the transplants of 4C12-treated animals beat strongly and showed increased accumulation of Foxp3(+) Tregs within the graft and decreased infiltration of inflammatory cells.

Conclusions: TNFRSF25 agonists expand Tregs in vivo and delay allograft rejection.
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http://dx.doi.org/10.1097/TP.0b013e318264d3efDOI Listing
September 2012

Clinical-scale isolation of interleukin-2-stimulated liver natural killer cells for treatment of liver transplantation with hepatocellular carcinoma.

Cell Transplant 2012 ;21(7):1397-406

Department of Surgery, Division of Liver and Gastrointestinal Transplantation, University of Miami Miller School of Medicine, 1801 NW 9th Avenue, Miami, FL 33136, USA.

Tumor recurrence is the main limitation of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and can be promoted by immunosuppressants. However, there is no prevention or treatment for HCC recurrence after LT. Here we describe a clinical-scale method for an adoptive immunotherapy approach that uses natural killer (NK) cells derived from deceased donor liver graft perfusate to prevent tumor recurrence after LT. Liver mononuclear cells (LMNCs) that were extracted from deceased donor liver graft perfusate contained a high percentage of NK cells (45.0 ± 4.0%) compared with peripheral blood mononuclear cells (PBMCs) (21.8 ± 5.2%) from the same donor. The CD69 activation marker and the natural cytotoxicity receptors, NKp44 and NKp46, were expressed at high levels in freshly isolated liver NK cells. Furthermore, interleukin-2 (IL-2)-stimulated NK cells showed greater upregulation of activation markers and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is critical for NK cell-mediated antitumor cell death and increased production of interferon. Moreover, IL-2 stimulation induced LMNCs to exhibit a strong cytotoxicity against NK-susceptible K562 target cells compared with PBMCs (p < 0.01). Finally, we also showed that the final product contained a very low T-cell contamination (0.02 ± 10(6) cells/kg(-1)), which reduces the risk of graft-versus-host disease (GVHD). Collectively, our results suggest that the adoptive transfer of IL-2-stimulated NK cells from deceased donor liver graft perfusate could be a promising treatment for LT patients with HCC.
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http://dx.doi.org/10.3727/096368911X627589DOI Listing
August 2013

Liver transplantation with preservation of the inferior vena cava: lessons learned through 2,000 cases.

J Am Coll Surg 2012 Apr 23;214(4):691-8; discussion 698-9. Epub 2012 Feb 23.

University of Miami Miller School of Medicine, Department of Surgery, Miami, FL 33136, USA.

Background: We aim to demonstrate the utility and efficacy of the "piggyback technique" (PBT); liver transplant (LT) with caval preservation.

Study Design: Adult LTs were performed with intent to use the PBT except in cases of juxtacaval malignancy or technical difficulty. Hepatic venous outflow was established between the donor suprahepatic cava and the joined ostia of all recipient suprahepatic veins. Technical variants with the donor cava and recipient retrohepatic cava were used as needed. The experience was divided into 2 eras: E1 (1994-2002), E2 (2002-2010).

Results: We completed 945 of 1080 LTs in E1 (87.5%) and 851 of 920 LTs in E2 (92.5%) using the PBT. Thirty day mortality was 4.6% in E1, 3% in E2 (p = 0.02) with 2 intra-operative deaths in E1. One, 3, 5 year patient survival was 83.7, 75.6, 69.3% in E1 vs. 86, 78.4, 73.8% in E2 (p = 0.057). Graft survival was 77.7, 69, 62.3% in E1 vs. 84, 76.2, 71.2% in E2 (p < 0.0001). Median operative time and hospital length of stay improved in E2 (p < 0.0001, 0.0001). Outflow variants were used more frequently in E2 (11.3% vs. 6.1%). Nine patients (0.5%) developed outflow obstruction, 6 in E1, and 3 in E2. Twice, it was recognized and corrected intraoperatively. Seven patients presented with refractory ascites. Six were successfully treated (4 balloon dilatation, 2 surgical revision), one patient died after attempted dilatation.

Conclusions: The PBT can be used as the preferred technique in adult LT. With experience, the technique was used more frequently, with more variants, with improved outcomes. Outflow obstruction was a rare complication.
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http://dx.doi.org/10.1016/j.jamcollsurg.2011.12.039DOI Listing
April 2012

Peripheral blood gene expression analysis in intestinal transplantation: a feasibility study for detecting novel candidate biomarkers of graft rejection.

Transplantation 2011 Dec;92(12):1385-91

Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Miami, FL, USA.

Introduction: We investigated the putative candidate biomarkers of graft rejection in peripheral blood of intestinal transplant patients.

Materials And Methods: Peripheral blood gene expression analysis was performed in intestinal transplant patients. The results were matched with concurrent graft biopsies using bioinformatics.

Results: Peripheral blood samples (n=11), of 3 adult patients [transplant day (n=1), no rejection (n=1), minimal rejection (n=2), mild rejection (n=5) and severe rejection (n=2)] were collected. Bioinformatics: Enrichment Analysis: The three most affected pathways differentially expressed in rejection versus a pool of healthy volunteers were related to protein translation: translation initiation, translation elongation termination, and translation in mitochondria, with p-values for all rejection stages in all patients in the 10-4 to 10-18 range. No significant enrichment was observed for these categories in the day of transplant sample. In addition to translation, significant enrichment of several immune response categories was observed in rejection samples. Subsequent gene set enrichment analysis verified these results. The level of enrichment was very high (p-values of 10-5-10-60) and increased with the level of rejection in all patients. Genes significantly down-regulated in translation related gene sets included ribosomal proteins RPL13A, RP L22, RPS23, RPL13 and RPL10A, that could be used as potential biomarkers for future experiments.

Conclusion: In this pilot study we found a list of genes (involved in translation) significantly downregulated in the peripheral blood of three intestinal transplant patients during rejection. These results will be verified in further studies with increased number of patients and with isolation of peripheral blood subpopulations.
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http://dx.doi.org/10.1097/TP.0b013e3182370db1DOI Listing
December 2011

The effect of donor-recipient cytomegalovirus serology on adult liver transplantation: a single center experience.

Transplantation 2011 Nov;92(9):1051-7

Division of Transplantation, Department of Surgery, University of Miami School of Medicine, Miami, FL 33136, USA.

Introduction: We investigated the outcomes of adult liver transplants, according to their donor-recipient cytomegalovirus (CMV) serology.

Materials And Methods: We included in the study all adult primary liver transplants, from January 1, 2002, to December 31, 2005. Follow-up was until December 31, 2007. According to the donor-recipient CMV serology, patients were divided into positive-negative (PN), positive-positive, negative-negative, and negative-positive groups, and all received CMV prophylaxis for 4 months posttransplantation. Hepatitis C patients received conventional immunosuppression, whereas all other patients received either conventional treatment or alemtuzumab (Campath-1H) induction.

Results: We studied 438 adult liver transplants. Comparisons were made between high-risk group patients (PN) versus all others: 5-year patient survival was 74.31% vs. 78.8%, (P=NS) and graft survival 63.87% vs. 74.77%, (P=0.042). Five-year freedom from rejection was 42.84% vs. 51.95% (P=0.036). CMV infection (n=3) or disease (n=27) was observed in 30 patients (PN [n=23], positive-positive [n=6], and negative-positive [n=1]). Incidence of CMV infection was 9.8% overall and 34.84% and 2.5%, respectively, for the PN group versus all others (P=0.0000). Patients who received Campath-1H induction did not have an increased incidence of CMV infections compared with those who received conventional immunosuppression.

Conclusions: In our center, in adult liver transplantation, CMV donor-recipient PN serology is associated with rejection, graft survival, and CMV infection but is not correlated with patient survival, Epstein-Barr virus (EBV) occurrence, or viral hepatitis recurrence. The introduction of more potent induction immunosuppression did not accentuate these negative outcomes.
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http://dx.doi.org/10.1097/TP.0b013e31822eb1f9DOI Listing
November 2011

Association between donor-specific antibodies and acute rejection and resolution in small bowel and multivisceral transplantation.

Transplantation 2011 Sep;92(6):709-15

Division of Transplantation, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

Background: Donor-specific antibodies (DSA) are associated with acute kidney graft rejection, but their role in small bowel/multivisceral allograft remains unclear. We carried out a prospective study to understand the impact of DSA in the setting of intestinal allograft rejection.

Methods: Thirteen patients (15 grafts) were serially evaluated for DSA levels pre- and posttransplant. DSA was determined by Luminex and the results were interpreted as fluorescence intensity (FI), with FI more than 3000 considered positive.

Results: The clinical rejection episodes in allografts were significantly associated with the presence of DSA (P=0.041).We obtained 291 biopsy samples from graft ileum and date-matched DSA assay reports. Sixty-three (21.65%) of the biopsies showed acute rejection. The appearance of DSA were preformed (n=5, anti-human leukocyte antigen class II=3, anti-class I and II=2), de novo (n=4, 15.25±4.72 days after transplantation, anti-class II=1, and anti-class I and II=3) and never (n=6). Among the 63 biopsies, 30(47.6%) had significant correlations with positive DSA (kappa=0.30, P<0.001) and manifested severe rejection grade (P=0.009).

Conclusions: In this cohort of small bowel/multivisceral transplantation patients, there was a high incidence of DSA. The presence of DSA should alert the clinical team of a higher risk of rejection, and reduction of the FI is clinically associated with resolution. Serial endoscopy guided biopsies combined with simultaneous DSA measurement in postintestinal transplantation follow-up is an effective means of screening for cellular and humoral-based forms of acute rejection.
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http://dx.doi.org/10.1097/TP.0b013e318229f752DOI Listing
September 2011

Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies.

Transpl Int 2011 Jul 9;24(7):697-707. Epub 2011 May 9.

Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

Small bowel transplantation (SBT) is becoming a preferred treatment for patients with irreversible intestinal failure. Despite continuous improvement of immunosuppression, SBT is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need for reliable detection markers and novel immunosuppressive strategies that can achieve better control of ACR. We hypothesized that particular transcriptomes provide critical regulation of the intragraft immune response. The aim of our study was to detect potential molecular biomarkers for identifying ACR in minute mucosal biopsies. We examined 30 intestinal mucosal biopsies (AR/NR; 17/13) obtained from recipients after SBT or multivisceral transplantation. We utilized TaqMan® Gene Signature Arrays (immune, inflammation and apoptosis) and investigated the expression of 280 genes. As one of our validations, we performed immunohistochemistry for selected targets. We detected 252 mRNAs in total, 92 of which were found with significantly different expression levels between the AR and NR groups. Immunohistochemistry showed significantly increased staining for IL1R2, ICAM1, GZMB, and CCL3 (P < 0.05) during ACR. For the first time, we characterize the potential molecular changes that are associated with modulation of histological appearances of intestinal ACR. These differences in transcriptome patterns can be used to identify robust biomarkers and potential novel therapeutic targets for immunosuppressive agents.
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http://dx.doi.org/10.1111/j.1432-2277.2011.01259.xDOI Listing
July 2011

Long-term follow-up of 23 operational tolerant liver transplant recipients.

Transplantation 2010 Dec;90(12):1556-61

Division of Transplantation, Department of Surgery, University of Miami School of Medicine, Highland Professional Building, Miami, FL, USA.

Introduction: This is a follow-up of a withdrawal study that we previously performed on 104 liver transplant patients in which immunosuppression was gradually withdrawn over a period of 3 years. Eighty-one patients were not able to be withdrawn (rejectors), and 23 patients were successfully weaned off immunosuppression (tolerants).

Methods: In this study, we present their follow-up after the end of the withdrawal study: we compared the results of the tolerant patients (n=23) with those of the rejectors (n=81). Follow-up was until February 2010.

Results: Operational tolerant patients were off immunosuppression for an average of 7.27±0.28 years. Patient survival in the tolerant and the rejector groups was 63.66% and 74.25%, respectively (P=not significant). A patient in the rejector group received two retransplants for chronic rejection. In the rejector group, 19 patients presented 26 rejection episodes: clinically suspected (n=19) and biopsy-proven mild (n=4), moderate (n=2), and severe (n=1) rejection episodes. A tolerant patient had a moderate rejection episode of 5.3 years after immunosuppression withdrawal. In the rejector group, five patients received a kidney transplant and four more are on dialysis versus a tolerant patient on dialysis. Freedom from rejection in the tolerant and rejector groups was 95% and 73%, respectively (P<0.05), and freedom from renal replacement treatment was 83.33% vs. 44.58%, respectively (P=not significant).

Conclusions: Long-term outcomes of operationally tolerant liver transplant patients are at least as good as those of control patients. Operational tolerance is not a permanent state, and continuous vigilance is required to detect rejection episodes.
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http://dx.doi.org/10.1097/TP.0b013e3182003db7DOI Listing
December 2010

Liver transplantation for hepatocellular carcinoma in the model for end-stage liver disease era.

J Am Coll Surg 2010 May;210(5):727-34, 735-6

Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

Background: Since March 2002, the United Network for Organ Sharing liver allocation policy has given extra priority to patients with hepatocellular carcinoma (HCC) who meet specific medical criteria. This study reviews our experience with liver transplantation for HCC under this system.

Study Design: Between March 2002 and April 2009, 244 patients with HCC underwent primary liver or liver-kidney transplantation under the current allocation system at the University of Miami. Outcomes including HCC recurrence-free survival (RFS) and patient survival (PS) were assessed retrospectively. Clinical variables that predicted outcomes were analyzed.

Results: The median time from listing to transplantation was 48 days. The median follow-up was 27.4 months, with an observed recurrence rate of 10.7%. The RFS rates at 1, 3, and 5 years after transplantation were 96.0%, 89.0%, and 83.6%, respectively. The PS rates at 1, 3, and 5 years after transplantation were 86.3%, 71.5%, and 61.7%, respectively. Among patients diagnosed with T2 HCC, a trend toward improved RFS was observed for those who received preoperative ablative therapy; PS was similar (p > 0.05). Outcomes (RFS and PS) for patients with T3 HCC were similar to those in patients with T2 HCC (p > 0.05). Patients with an alpha-fetoprotein >100 ng/mL had an RFS that was inferior to that in patients with an alpha-fetoprotein < or =100 ng/mL (p < 0.0001).

Conclusions: Under the current allocation system, transplantation for HCC results in excellent RFS; PS depends on factors other than HCC; the value of preoperative ablative therapy for patients with T2 HCC is uncertain; the current criteria could be expanded to include selected patients with T3 HCC; and an elevated AFP level is associated with an increased risk of HCC recurrence after transplantation.
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http://dx.doi.org/10.1016/j.jamcollsurg.2010.01.007DOI Listing
May 2010

Effect of liver transplantation on spleen size, collateral veins, and platelet counts.

World J Surg 2010 Feb;34(2):320-6

Miami Transplant Institute, Division of Liver and GI Transplantation, Department of Surgery, University of Miami Miller School of Medicine, Highland Professional Bldg., 1801 NW 9th Avenue, 3rd Floor, Miami, FL 33136, USA.

Background: The aim of this study was to evaluate the effect of liver transplantation on the spleen size, spontaneous splenorenal shunt (SRS) function, and platelet counts in patients with hypersplenism.

Methods: Between December 2001 and February 2007, 462 adult patients underwent orthotopic liver transplantations (OLTX) at our institution. Of these patients, CT or MRI information was reviewed retrospectively in 55 patients. Volume measurements of the spleen and liver, spleen/liver volume ratio (S/L ratio), presence and size of SRS, and platelet counts were evaluated before and after OLTX.

Results: Mean spleen volume decreased from 827 +/- 463 ml to 662 +/- 376 ml after OLTX (p < 0.01). Five (11%) patients returned to normal-range spleen size after OLTX. SRS was observed in 19 patients before OLTX (35%). The diameter of SRS also significantly decreased from 1.0 +/- 0.5 cm before OLTX to 0.7 +/- 0.5 cm after OLTX (p < 0.05). SRS disappeared in 16% of patients (3/19). S/L ratio significantly decreased from 0.65 +/- 0.33 to 0.38 +/- 0.17 (p < 0.01) after OLTX. Platelet counts significantly increased after OLTX (p < 0.01). Improvement of the platelet count in the group with postoperative S/L ratio >0.35 was not as good as that in the group with S/L ratio <0.35 (p < 0.01).

Conclusions: Spleen size and SRS size became significantly smaller after OLTX. However, patients with postoperative S/L ratio >0.35 tend to have lower platelet counts after OLTX.
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http://dx.doi.org/10.1007/s00268-009-0314-xDOI Listing
February 2010

Heterotopic uterus transplantation in a swine model.

Transplantation 2009 Aug;88(4):465-9

Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

Background: The aim of our study was to examine the feasibility of allogeneic uterine transplantation in a large animal model.

Methods: We performed heterotopic uterine transplants in genetically defined mini-pigs. Immunosuppression was tacrolimus administered intravenously for the first 12 days posttransplantation followed by oral cyclosporine maintenance immunosuppression. The graft was transplanted heterotopically in the lower abdominal cavity of the recipient. The vaginal vault was exteriorized as a stoma in the lower right abdominal wall. The uterine grafts were followed with endoscopies and biopsies.

Results: Ten transplants were performed. Follow-up was until July 2008. At the end of the follow-up period, 5 animals were alive and healthy, 0.5 to 12 months posttransplantation. There were 5 deaths due to pneumonia (n=1), intussusception of the graft (n=1), cardiorespiratory arrest during anesthesia (n=1), and complications of the stoma (n=2). Acute rejections of the graft presented during the 2nd and 3rd month posttransplantation were treated successfully with increase of the maintenance immunosuppression and steroids. Other complications included prolapse and infections of the graft stoma. Pathological changes seen in the endometrial biopsies included acute rejection and acute endometritis.

Conclusion: These findings demonstrate that successful uterus transplantation in a large animal model (miniature swine) is feasible using this heterotopic model, and it can be useful for the study of these transplants.
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http://dx.doi.org/10.1097/TP.0b013e3181b07666DOI Listing
August 2009

Mass clamping of the hilum to facilitate difficult hepatectomy during liver transplantation: a single center 10 year experience.

Ann Surg 2009 Aug;250(2):273-6

Division of Transplantation, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

Introduction: Classic dissection of the hilar structures during the hepatectomy portion of the liver transplant procedure is sometimes extremely difficult and even dangerous. In such cases, clamping of the hepatic hilar structures en mass can be an effective alternative. In this study, we describe our center's experience with this technique.

Patients And Methods: This is a retrospective analysis of all patients who received a liver allograft using this technique at our center, between September 1996 and September 2007 (n = 150). Postoperative follow-up was through November 30, 2007.

Results: One hundred fifty patients underwent 155 liver transplants using hilar mass clamping. These cases represent 7% of the total number of cases performed at our center during that time interval (n = 2219). This included 93 male and 57 female patients, 18 children and 132 adults. There were 103 primary liver transplants, 52 retransplants. Three of the primary transplants were combined liver/kidney transplants. In 7 cases (4.5%), portacaval hemitransposition was performed to establish portal flow.The decision to perform the hepatectomy with mass clamping of the hilar structures was an intraoperative judgment made when severe vascular adhesions and scarring of the hilum (n = 137) or extensive hilar varices (n = 18) were encountered. The hilar pathology was often associated with hepatic artery (n = 15) or portal vein thrombosis (n = 14).Mean surgical time was 11.33 +/- 0.28 hours. Average blood replacement was 26.27 +/- 2.05 units of packed red blood cells. One patient died intraoperatively (0.64%) while perioperative (30 day) mortality was 6.4%. Venovenous by pass was used in 1 patient (0.64%).One and 5 year patient survival was 75.3% and 61.2%, respectively. One and 5 year graft survival was 73.7% and 48.2%, respectively. There was no patient mortality, graft loss, or technical complications that could be attributed to the mass clamp technique.

Conclusion: Mass clamping of the hepatic hilum can be an effective alternative to classic hilar dissection in cases when the latter is difficult or impossible.
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http://dx.doi.org/10.1097/SLA.0b013e3181b17161DOI Listing
August 2009

Successful treatment with bortezomib of a refractory humoral rejection of the intestine after multivisceral transplantation.

Clin Transpl 2009 :465-9

Department of Surgery, University of Miami School of Medicine, Miami, Florida, USA.

Graft rejection is a serious complication after intestinal and multivisceral transplantation. Classic anti-rejection strategies often focus on addressing the cellular component, however mounting evidence suggests that antibody mediated rejection may also play an important role in patient and graft survival. Bortezomib, a proteasome inhibitor used in the treatment of multiple myeloma, has been found to be useful in treating antibody mediated rejection in kidney transplant recipients. The following case illustrates how bortezomib was used to successfully reverse refractory rejection in a patient following multivisceral transplantation. While the rejection was able to be controlled, this patient's course was complicated by an aggressive viral infection after bortezomib therapy. Bortezomib may be a useful agent in the treatment of rejection after intestinal and multivisceral transplantation; however more data is needed to assess its impact on infectious complications in this complex group of patients.
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July 2010

[Critical value of citrulline for complications of intestinal transplant graft].

Rev Assoc Med Bras (1992) 2008 Sep-Oct;54(5):426-9

Departamento de Cirurgia da Irmandade, Santa Casa de Misericórdia de São Paulo, SP.

Objective: A biochemical marker for detection of acute cellular rejection following small intestine transplantation has been sought. Citrulline, a non- protein amino acid synthesized mainly by functioning enterocytes, has been proposed. Trial sensitivity has been reportedly high but with low specificity. Thus, the goal was to determine, in a sufficiently large analysis, the significant value of citrulline level in the post-transplant setting, which would correlate with complications such as rejection and infection.

Methods: Since March, 2004 2,135 dried blood spot (DBS) citrulline samples were obtained from 57 small intestine transplant recipients three months or more after post-transplant, i.e., once the expected period of recovery in the citrulline levels had occurred.

Results: Using a <13 vs. > 13 micromoles/L cut off point, sensitivity of DBS citrulline for the detection of moderate or severe ACR was extremely high (96.4%). Furthermore, specificity estimates (given the absence of ACR and these particular infections), while controlling for time-to-DBS sample were reasonably high (54%-74% in children and 83%-88% in adults), and the negative predictive value (NPV) was >99%.

Conclusion: Citrulline is a non-invasive marker to evaluate problems of the intestinal graft after three months post-transplant. Due to the high NPV, a moderate or severe ACR can be ruled out, based exclusively on knowledge of a high value for DBS citrulline.
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http://dx.doi.org/10.1590/s0104-42302008000500016DOI Listing
July 2009

Herpes zoster infection after liver transplantation in patients receiving induction therapy with alemtuzumab.

Clin Transplant 2008 Jul-Aug;22(4):502-7. Epub 2008 Jul 8.

Department of Infectious Diseases, Miller School of Medicine, Miami, FL 33136, USA.

Background: The incidence of herpes zoster (HZ) infection in liver transplant recipients prior to the use of induction therapy with monoclonal antibodies has been reported as being 1.2-18%. We studied the occurrence of HZ in liver transplant recipients that received induction therapy with alemtuzumab (Campath 1H).

Material And Methods: This was a retrospective review of primary liver transplant recipients who received alemtuzumab as induction therapy at our center. HZ infection was diagnosed clinically as the presence of a characteristic vesicular rash in a dermatomal distribution without any further virological confirmation.

Results: A total of 118 liver transplant recipients were treated with alemtuzumab between August 2002 and August 2005. Twelve patients developed HZ infection, and the cumulative probability of a patient developing HZ infection by 36 months post-transplant +/-1 SE was estimated as 16.5 +/- 5.0%. The median time for onset of the infection was 10.2 months (range 4.7-30.7) after the transplant. All patients had only one dermatomal distribution, and none developed systemic infection or complications such as postherpetic neuropathy. All patients except one were treated with systemic intravenous acyclovir. One patient received famciclovir. All of the patients had received ganciclovir during the post-transplant period but were not receiving any other antiviral medication at the time of the infection.

Conclusion: Herpes zoster infection has previously been reported as a frequent complication of liver transplantation. Our study suggests that it occurs in approximately 16% of patients receiving induction therapy with alemtuzumab. Although alemtuzumab is a powerful immunosuppressive agent and there is still little information regarding its long-term safety when used in liver transplantation, our data do not suggest any increase in the occurrence and complications of HZ.
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http://dx.doi.org/10.1111/j.1399-0012.2008.00816.xDOI Listing
December 2008

Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation.

Transplantation 2007 Nov;84(9):1077-81

Departments of Surgery, University of Miami School of Medicine, Miami, FL 33101, USA.

Background: Serum citrulline is a marker for acute cellular rejection (ACR) after intestinal transplantation; however, its clinical utility has not yet been established. The goal of this study was to determine clearcut serum levels beyond which the diagnosis of acute rejection could be supported or refuted, and predictors of citrulline levels posttransplant from which more accurate estimates of sensitivity and specificity could be obtained.

Methods: Since March 2004, we obtained 2135 dried blood spot (DBS) citrulline samples from 57 intestinal transplant recipients at or beyond 3 months posttransplant. Stepwise linear regression was performed to determine the most significant multivariable predictors of the patient's DBS citrulline level.

Results: Seven characteristics were associated with a significantly lower citrulline in multivariable analysis: presence of mild, moderate, or severe ACR; presence of bacteremia or respiratory infection; pediatric age; and time from transplant to DBS sample (P<0.00001 in each case). Using a <13 vs. > or =13 micromoles/L cutoff point, the sensitivity for detecting moderate or severe ACR and the negative predictive value were high (96.4% and >99% respectively). Specificity was 54% to 74% in children and 83% to 88% in adults.

Conclusions: Citrulline levels <13 micromoles/L should alert the clinical team that a serious problem (rejection or infection) could be looming in a previously stable intestinal recipient. Levels > =13 micromoles/L practically rule out moderate or severe rejection.
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http://dx.doi.org/10.1097/01.tp.0000287186.04342.82DOI Listing
November 2007

100 multivisceral transplants at a single center.

Ann Surg 2005 Oct;242(4):480-90; discussion 491-3

Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Objective: The objective of this study was to summarize the evolution of multivisceral transplantation over a decade of experience and evaluate its current status.

Summary Background Data: Multivisceral transplantation can be valuable for the treatment of patients with massive abdominal catastrophes. Its major limitations have been technical and rejection of the intestinal graft.

Methods: This study consisted of an outcome analysis of 98 consecutive patients who received multivisceral transplantation at our institution. This represents the largest single center experience to date.

Results: The most common diseases in our population before transplant were intestinal gastroschisis and intestinal dysmotility syndromes in children, and mesenteric thrombosis and trauma in adults. Kaplan Meier estimated patient and graft survivals for all cases were 65% and 63% at 1 year, 49% and 47% at 3 years, and 49% and 47% at 5 years. Factors that adversely influenced patient survival included transplant before 1998 (P = 0.01), being hospitalized at the time of transplant (P = 0.05), and being a child who received Campath-1H induction (P = 0.03). Among 37 patients who had none of these 3 factors (15 adults and 22 children), estimated 1- and 3-year survivals were 89% and 71%, respectively. Patients transplanted since 2001 had significantly less moderate and severe rejections (31.6% vs 67.6%, P = 0.0005) with almost half of these patients never developing rejection.

Conclusions: Multivisceral transplantation is now an effective treatment of patients with complex abdominal pathology. The incidences of serious acute rejection and patient survival have improved in the most recent experience. Our results show that the multivisceral graft seems to facilitate engraftment of transplanted organs and raises the possibility that there is a degree of immunologic protection afforded by this procedure.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1402343PMC
http://dx.doi.org/10.1097/01.sla.0000183347.61361.7aDOI Listing
October 2005

The role of donor bone marrow infusions in withdrawal of immunosuppression in adult liver allotransplantation.

Am J Transplant 2005 Mar;5(3):608-13

Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Miami, Florida, USA.

We investigated the role of donor bone marrow cell (DBMC) infusions in immunosuppression withdrawal in adult liver transplantation. Patients enrolled were at least 3 years post-transplantation, with stable graft function. Forty-five (study group: G1) received DBMC, and 59 (control group: G2) did not. Immunosuppression was reduced by one third upon enrollment, by another third the second year of the study and was completely withdrawn the third year. Patient and graft survival were similar between the two groups. Although rejection episodes were significantly less in G1 the first 2 years of the study (35% vs. 57%, p = 0.016), there was no significant difference overall (74% vs. 81%, p = 0.14). Until February 2004, 20 patients, 10 in each group, were immunosuppression free for 1-3 years. Approximately 20% of long-term survivors of liver transplantation can successfully discontinue their immunosuppression. DBMC infusions, do not increase this likelihood.
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http://dx.doi.org/10.1111/j.1600-6143.2004.00743.xDOI Listing
March 2005

Preliminary experience with alemtuzumab (Campath-1H) and low-dose tacrolimus immunosuppression in adult liver transplantation.

Transplantation 2004 Apr;77(8):1209-14

Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Miami, Florida 33136, USA.

Background: The administration of alemtuzumab (Campath-1H [C1H]; Berlex Laboratories, Montville, NJ) at transplantation prevents a vigorous immune response and is believed to allow a gradual engagement of the host immune system. We report our preliminary experience with C1H and tacrolimus (Tac) immunosuppression in adult liver transplantation.

Methods: We administered C1H and low-dose Tac to 40 adult recipients of cadaveric liver allografts between December 2001 and April 2003. A control group who met the same eligibility criteria consisted of 50 liver transplant recipients treated with our standard Tac and steroids protocol.

Results: Baseline characteristics and patient and graft survival were similar (P >0.15). The incidence of acute rejection was significantly lower during the first 2 months posttransplantation (P =0.002) and slightly lower overall in the study group versus the control group at 12 months (46% vs. 55%, P =0.12, log-rank test). Median time to rejection among those experiencing rejection was significantly longer in the study group versus control group (2.76 vs. 0.34 months, P =0.0007). The mean Tac dose, 12-hr trough level, and percentage of patients receiving maintenance steroids were significantly lower in the group receiving C1H and Tac (P <0.0001 during the first 3 months, P <0.05 thereafter), as were the mean creatinine levels (P <0.05) and incidence of nephrotoxicity (P =0.004, conversion from Tac to other agents). Finally, in the group receiving C1H/Tac, patients with an average Tac trough level less than 6.5 ng/mL during the first 2 months post-transplantation demonstrated a significantly higher rejection rate beyond that time (P =0.02).

Conclusion: C1H and low-dose Tac seems to be at least as effective as our standard Tac and steroids regimen in preventing acute rejection in adult liver allotransplantation with less renal toxicity and less use of maintenance steroids.
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http://dx.doi.org/10.1097/01.tp.0000116562.15920.43DOI Listing
April 2004

Partial abdominal evisceration, ex vivo resection, and intestinal autotransplantation for the treatment of pathologic lesions of the root of the mesentery.

J Am Coll Surg 2003 Nov;197(5):770-6

Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Miami, FL, USA.

Background: Resection of lesions of the root of the mesentery with established techniques is difficult and at times impossible because of their proximity to the blood supply of the intestine. Damage of the superior mesenteric vessels necessitates resection of the intestine, resulting in short bowel syndrome and intestinal failure.

Study Design: We describe a surgical technique drawn from our experience in intestinal transplantation in which the root of the mesentery (including the lesion) and the head or the entire pancreas, duodenum, small intestine, and part of the colon are excised en bloc and preserved in a cold solution. Resection of the lesion is performed in a bloodless field ex vivo, and the salvaged intestine is reimplanted in the abdominal cavity. We performed this procedure in four patients, two adult and two pediatric, who had extensive neoplasms of the root of the mesentery. Their underlying diseases were mesenteric fibroma, vascular dysplasia of the root of the mesentery, pancreatic cancer, and desmoid tumor.

Results: Local control of the lesions was achieved in all four cases, preserving at the same time enough small intestine to avoid short bowel syndrome. All patients survived the operation and live on enteral nutrition 6 to 49.5 months after the procedure.

Conclusions: The procedure of partial abdominal exenteration, ex vivo resection, and autotransplantation is an extension of our experience with intestinal transplantation. In selected cases, this technique may be useful in the treatment of extensive, otherwise unresectable lesions of the root of the mesentery.
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http://dx.doi.org/10.1016/s1072-7515(03)00756-7DOI Listing
November 2003

Alemtuzumab (Campath-1H) combined with tacrolimus in intestinal and multivisceral transplantation.

Transplantation 2003 May;75(9):1512-7

Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Florida 33136, USA.

Background: We combined alemtuzumab (Campath-1H, Berlex Laboratories, Montville, NJ) and tacrolimus (Tac) immunosuppression for intestinal and multivisceral transplantation.

Materials And Methods: A total of 21 adult patients received 24 grafts: 14 intestinal, nine multivisceral, and one liver-intestinal graft. Alemtuzumab was administered perioperatively in four doses with low-dose Tac (levels 10-15 ng/dL) and no maintenance steroids. Tac was substituted with sirolimus in case of Tac-related complications. Suspected or mild rejections were treated with steroids. Moderate rejections were treated with steroids or OKT3. Severe rejections were treated with OKT3.

Results: Of the 16 patients that were followed up for an average of 9 months, 12 are alive with functioning grafts. Two patients experienced severe rejection, three experienced moderate rejection episodes, and seven experienced mild acute rejection episodes. Four patients never developed acute rejection. Infectious complications included a cytomegalovirus enteritis and four fungal infections (related to central venous access).

Conclusions: The combination of alemtuzumab and Tac therapy without steroid use seems to efficiently prevent acute rejection in a significant number of patients without causing frequent opportunistic infections.
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http://dx.doi.org/10.1097/01.TP.0000060250.50591.39DOI Listing
May 2003

Preliminary experience with campath 1H (C1H) in intestinal and liver transplantation.

Transplantation 2003 Apr;75(8):1227-31

Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Miami, FL 33136, USA.

Background: The aim of this research was to study the efficacy of campath 1H in combination with low-dose tacrolimus immunosuppression for intestinal, multivisceral, and liver transplantation.

Methods: Campath 1H (0.3 mg/kg) was administered in four doses: Preoperatively, at the completion of the transplant, and on postoperative days 3 and 7. Tacrolimus levels were maintained between 5 to 10 ng/dL. Suspected or mild rejections were treated with steroids. Moderate or severe rejections were treated with OKT3.

Patients: We studied three groups of patients: adult recipients of intestinal or multivisceral transplants, high-risk pediatric recipients of small-bowel or multivisceral grafts, and adult liver-transplant recipients.

Results: Twenty-one adult intestinal recipients received 24 grafts. With follow-up of 2.4 to 16 months, 14 patients are alive and 14 grafts are functioning. Eleven high-risk pediatric intestinal recipients received 12 grafts. There were four mortalities in this group, and after a follow up of 1 to 8.5 months, four patients have not experienced a rejection episode. Five adult liver recipients received five grafts. With a follow-up of 3 to 6.2 months, all five patients are alive. There were no rejection episodes in this group, and none of them required steroid therapy.

Conclusions: This immunosuppressive regimen allows for the avoidance of maintenance adjuvant-steroid treatment in the majority of our patients. Our preliminary data show a trend toward a reduction of the incidence and the severity of rejection episodes, although we need to follow-up larger numbers of patients to confirm these results.
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http://dx.doi.org/10.1097/01.TP.0000065192.53065.50DOI Listing
April 2003

Host-derived enterocytes in intestinal grafts.

Transplantation 2002 Jul;74(1):120-38

Department of Surgery and Pathology, University of Miami School of Medicine, Florida, USA.

Replacement of donor lymphoid tissue by lymphocytes of recipient origin is an established phenomenon in small bowel transplants. However, replacement of donor epithelial cells of bowel grafts by host cells has not been demonstrated. The objective of our study was to determine whether donor enterocytes are replaced by host-derived enterocytes in the intestinal allograft. Graft biopsy specimens, obtained from five human male recipients of female intestine, were examined for the presence of male enterocytes. The biopsies dated from 90 to 770 days posttransplant. Formalin-fixed 3-microm specimen sections were stained for X and Y chromosomes by fluorescent in situ hybridization technique. Fluorescent microscopy of the stained sections identified male enterocytes in four patients, with a percentage of male cells ranging from 0.09% to 0.26% of the total enterocyte mass. Using the fluorescent in situ hybridization technique, we demonstrated the presence of host-derived male (XY) enterocytes in the female intestinal graft.
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http://dx.doi.org/10.1097/00007890-200207150-00020DOI Listing
July 2002