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

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.

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

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.

Analysis of acute and chronic rejection in multiple organ allografts from retransplantation and autopsy cases of multivisceral transplantation.

BACKGROUND: Small intestinal allografts in multivisceral transplantation are felt to be more susceptible to acute cellular rejection (ACR) and chronic rejection (CR) when compared with other allografts although there is little direct evidence for this impression. METHODS: A total of 48 cases of multiple allograft specimens (37 autopsy and 11 explanted allograft cases) from 41 patients were evaluated in this study. Histopathologic assessments were performed with special concern to ACR and CR in allografts. The numbers of allografts available for evaluation were liver 37, small intestine 47, stomach 41, pancreas 45, and large intestine 25. RESULTS: Among 48 cases, 15 cases showed ACR (ACR case) and 12 showed CR (CR case) in at least one organ. In ACR cases, there was a statistically significant difference of organ-specific susceptibility to ACR among multivisceral allografts with the small intestinal allograft being the most susceptible (P<0.05). Severe ACR were observed only in small and large intestinal allografts. In CR cases, there was no statistically significant difference of organ-specific susceptibility to CR among multivisceral allografts with a tendency for the pancreas allograft to be the most susceptible (P=0.35). CONCLUSIONS: Our study clearly indicated variation in organ susceptibility to ACR and CR. Small intestinal allografts were the most susceptible organ to ACR in frequency and severity. Pancreatic allografts may be more susceptible to CR in comparison with ACR.

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

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.

[Critical value of citrulline for complications of intestinal transplant graft]. / Valor crítico da citrulina para as complicações do enxerto no transplante de intestino.

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.

Outcomes after orthotopic liver transplantation in 15 HIV-infected patients.

BACKGROUND: Human immunodeficiency virus (HIV) infection has been associated with poor outcomes after orthotopic liver transplantation (OLT). Highly active antiretroviral therapy (HAART) has led to an increasing number of successful OLTs. The aim of this study was to examine survival and cause-specific mortality in HIV-infected patients after OLT at our institution. METHODS: A retrospective analysis of all HIV patients that underwent OLT was compared to all non-HIV patients undergoing OLT during the same period. Cumulative patient and cause-specific survival were calculated using Kaplan-Meier methods; the log-rank test was used to compare the two cohorts. Fifteen HIV-infected patients and 857 non-HIV patients underwent OLT between June 1, 1999 and May 1, 2006. RESULTS: The actuarial 1-, 2-, and 3-year survival rates posttransplant (+/-standard error) were 73.3% (+/-11.4%) for the HIV group (unchanged from 1 to 3 years) versus 86.9% (+/-1.2%), 82.0% (+/-1.4%), and 79.4% (+/-1.5%) for the non-HIV group. Cumulative survival among HIV-infected recipients was not different from the non-HIV population (P=0.20). A difference was observed between the two groups in mortality rates due to infectious causes: the percentage of HIV patients dying from infection was 26.7% (4 of 15) vs. 8.2% (70 of 857) in the non-HIV group (P=0.006). CONCLUSIONS: PostOLT survival was comparable in HIV and non-HIV recipients; however, HIV patients had significantly higher mortality from infectious complications. This difference occurred despite adequate control of HIV postOLT. These findings suggest that OLT can be safely performed for HIV-infected patients; however, these patients are at higher risk of mortality from infectious complications.

A cause-specific hazard rate analysis of prognostic factors among 877 adults who received primary orthotopic liver transplantation.

BACKGROUND: In orthotopic liver transplantation (OLT) distinct causes of graft failure (GF) and death with a functioning graft (DFG) exist. Prognostic factors for one failure type may be distinctly different from those predictive of other types, and an accurate portrayal of these relationships may more clearly explain each factor's importance. METHODS: A multivariable cause-specific hazard (CSH) rate analysis using Cox stepwise regression was performed among 877 adults who received primary OLT during 1996-2004 with tacrolimus+steroids as immunosuppression. RESULTS: Older donor age (P=0.004) implied greater primary dysfunction GF, while primary sclerosing cholangitis (PSC; P=0.0002) implied greater vascular thrombosis GF. Recurrent nonmalignant liver disease GF was higher among hepatitis C virus patients (P<0.00001), and younger recipient age (P=0.005) implied greater death from recurrent (metastatic) hepatocellular carcinoma. African-American race (P<0.00001), PSC (P=0.003), and younger recipient age (P=0.005) were independently associated with greater GF due to chronic rejection. Older donor age (P=0.003) implied greater infection DFG, while older recipient age (P=0.003) and pretransplant diabetes (P=0.03) were independently associated with greater cardiovascular/cerebrovascular DFG. Finally, most of these cause-specific predictors were not significant in an overall Cox model for graft survival. CONCLUSIONS: The CSH approach should be more widely used in investigations of prognostic factors. The result of older donor age implying greater primary dysfunction GF and infection DFG but having no association with other failure types demonstrates that its impact is specific to the graft's early posttransplant functional status. In addition, while recipient age was an important prognosticator, its direction of association reverses depending upon the outcome being analyzed.

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

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.

The importance of analyzing graft and patient survival by cause of failure: an example using pediatric small intestine transplant data.

BACKGROUND: Although graft and patient survival are vital in reporting overall results of clinical transplant studies, these outcomes do not account for distinct types of graft failure and death, which clearly exist in pediatric small intestine transplantation (Itx). The use of a cause-specific hazard (CSH) approach may provide more precise identification and thus greater insight as to why certain factors are prognostically important. METHODS: Among 119 pediatric patients who received primary Itx at our center since 1994, Cox model stepwise regression analyses were performed to identify prognostic factors for the following CSH rates: intestinal graft failure (IGF)/death due to rejection, death due to infection not triggered by IGF, and intestinal graft loss/death due to other causes. RESULTS: Two factors were associated with a significantly higher rate of developing IGF due to rejection (23 such failures): receiving an isolated intestine or liver-intestine transplant (P=0.00001) and receiving no induction agent (P=0.006). Conversely, age at transplant <1 year was the single factor associated with a significantly higher death rate due to infection (P=0.0005) (21 such deaths). Two characteristics were associated with a significantly higher death rate due to other causes: being in the hospital pretransplant (P=0.007) and not receiving daclizumab induction therapy (P=0.02) (24 such deaths). Although these four factors (transplant type/age/hospital status/induction therapy) were, for the most part, associated with graft/patient survival, the CSH analysis more precisely identified their prognostic value and achieved greater statistical power. CONCLUSIONS: A CSH approach should be used in conjunction with overall outcome analyses.

Utilization of dried blood spot citrulline level as a noninvasive method for monitoring graft function following intestinal transplantation.

BACKGROUND: Citrulline concentrations have been proposed as a marker for intestinal allograft rejection. We instituted dried blood spot (DBS) specimen monitoring of citrulline to simplify sample collection posttransplant. This study demonstrates the correlation between plasma and dried blood spot specimen citrulline concentrations after intestinal transplantation. METHODS: Plasma and DBS samples were analyzed by hydrophilic interaction chromatography tandem mass spectrometry. Comparison of the strength of linear correlation was made according to the type of surgery, sonication time, DBS citrulline levels, and the time interval between the blood sample collection and the assay date. RESULTS: A very strong linear correlation exists between the plasma and DBS citrulline concentrations (r=0.87; P<0.001). The correlation between plasma and DBS citrulline concentrations was maintained when evaluating only the intestinal transplant recipients. There was no significant difference in the strength of linear correlation according to sonication time, cirtrulline concentrations, or length of time to assay date. CONCLUSIONS: DBS citrulline monitoring will ease sample collection following intestinal transplantation and improve the ability to detect intestinal dysfunction and rejection by a noninvasive means.

Temporal relationships between acute cellular rejection features and increased mucosal fibrosis in the early posttransplant period of human small intestinal allografts.

BACKGROUND: Intestinal allograft biopsies limit histopathological analysis to the superficial layers of the bowel. These biopsies allow a reasonable assessment of the histological features of acute rejection, but characteristics of chronic injury in mucosal layers remain poorly defined because of the limitations posed by endoscopic sampling. Experimental work has inferred that intestinal mucosal fibrosis may be indicative of chronic rejection; however, a temporal, graded study of mucosal fibrosis has not been performed. METHODS: A total of 79 endoscopic intestinal allograft biopsies from 12 patients obtained at 3 to 120 days posttransplantation were evaluated. Fibrosis and individual parameters of acute cellular rejection were graded according to a semiquantitative scoring system and were evaluated for potential relationships with each other. RESULTS: We found that while acute rejection tends to occur early in the posttransplant period, fibrosis of the lamina propria increases at a later time, particularly in the third and fourth month. Several individual graded parameters of acute rejection had an association with fibrosis at the same time points. CONCLUSIONS: Fibrous replacement of the lamina propria in human endoscopic allograft biopsies occurs with advancing time after transplantation. Acute rejection precedes and may have some eventual impact upon the amount of fibrosis present. A measurement of the connective tissue component of bowel transplant tissue may serve as a harbinger of long-term enteral allograft dysfunction.

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

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.

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

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.

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

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.

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

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.

Burkitt s lymphoma variant of post-transplant lymphoproliferative disease (PTLD).

The occurrence of posttransplant lymphoproliferative disorder (PTLD) in solid organ allograft recipients can be quite varied in clinical presentation, histopathological characteristics and frequency. A variety of lymphomas can develop as a PTLD although some types appear infrequently and remain poorly understood in this clinical setting. In this report, we describe two cases of Burkitt s lymphoma presenting as a PTLD following liver transplantation. The recipients were 12 and 44 years of age and displayed gastrointestinal involvement by the tumors several years following transplant. The tumors displayed the typical histological features of Burkitt s lymphoma and were markedly positive for EBV. The tumors displayed similar immunophenotypic characteristics by flow cytometry and had rearrangements of the immunoglobulin J-H heavy chain. The tumors required aggressive chemotherapy and a cessation of immunosuppressive therapy. This report demonstrates that Burkitt s type lymphomas can develop in the posttransplant setting and that these tumors contain morphologic, cytofluorographic and molecular features identical to Burkitt s lymphomas that occur in non-transplant patients. Our experience is that these PTLD- Burkitt s lymphomas behave aggressively and require intensive chemotherapeutic intervention.

Preoperative embolization of the graft superior mesenteric artery assists graft enterectomy in intestinal transplant recipients.

BACKGROUND: Graft enterectomy after intestinal graft failure is challenging. We report our experience in preoperative embolization of graft superior mesenteric artery (SMA) to facilitate intestinal graft removal. METHODS: A total of 22 isolated intestinal transplant recipients underwent graft enterectomy from July 1997 to February 2011 at the Miami Transplant Institute, Miller School of Medicine, University of Miami, of whom 6 patients underwent embolization of graft SMA seven times before graft enterectomy. RESULTS: The mean (SD) estimated blood loss in patients with or without embolization was 600 (173) versus 1437 (328) mL, respectively (P=0.02). The mean operation time in patients with or without embolization was 5.2 (1.2) versus 8.7 (1.3) hr, respectively (P=0.04). The mean change between preoperative and postoperative serum creatinine in patients with or without embolization was 0.2 (0.05) versus 0.16 (0.04), respectively (P=0.12). In patients with embolization, the warm ischemia time (from embolization to removal of the graft) was 6.9 (1.1) hr (range, 6-8.5 hr). Intraoperative and postoperative (24 hr) pH values were 7.36 (0.1) and 7.34 (0.1), respectively (P=0.71); intraoperative and postoperative (24 hr) lactate levels were 1.77 (0.8) and 1.56 (0.5) mmol/L, respectively (P=0.57). CONCLUSIONS: Preoperative embolization of graft SMA is a useful alternative to assist graft enterectomy in intestinal transplant recipients without causing severe acidosis, renal impairment, and hemodynamic instability.

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

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.

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

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.