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.

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.

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

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.

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.

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.

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

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.

Liver transplantation for severe hepatic trauma: experience from a single center.

Liver transplantation has been reported in the literature as an extreme intervention in cases of severe and complicated hepatic trauma. The main indications for liver transplant in such cases were uncontrollable bleeding and postoperative hepatic insufficiency. We here describe four cases of orthotopic liver transplantation after penetrating or blunt liver trauma. The indications were liver failure, extended liver necrosis, liver gangrene and multiple episodes of gastrointestinal bleeding related to portal hypertension, respectively. One patient died due to postoperative cerebral edema. The other three patients recovered well and remain on immunosuppression. Liver transplantation should be considered as a saving procedure in severe hepatic trauma, when all other treatment modalities fail.

Intestinal and multivisceral transplantation at the University of Miami.

At the University of Miami Liver and GI Transplant Program, over 300 intestinal transplant procedures were performed in the last 15 years in adult and pediatric recipients. Good patient and graft survival rates are now achievable. Rejection remains the complication that is most difficult to prevent and manage. Induction with antilymphocyte agents, followed by maintenance with tacrolimus, is the preferred immunosuppression protocol at our center. We have expanded the use of multivisceral transplantation in pediatric recipients with short gut and significant liver dysfunction from parenteral nutrition. We also advocate the use of large intestine as part of the intestinal graft as well as inclusion of the spleen in multivisceral grafts, which in our experience can be safely accomplished. The future of intestinal transplantation lies in the use of noninvasive markers of intestinal rejection, and continued refinements in immunosuppression protocols.

[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.

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

OBJETIVO: Analisar, numa ampla amostra, o valor crítico da citrulina que confirma a presença das principais complicações do enxerto: rejeição e infecção. MÉTODOS: Foram coletadas 2135 amostras de citrulina sérica, na forma de gota de sangue seca, de 57 doentes submetidos a transplante de intestino/multivisceral no Jackson Memorial Hospital na Universidade de Miami, de março de 2004 a abril de 2006. Todas as amostras são do pós-operatório três meses em diante, passada a conhecida curva de elevação da citrulina após a recuperação das lesões causadas pela isquemia e reperfusão do pós-transplante. RESULTADOS: Utilizando um valor limite menor que 13 µmoles/L, a sensibilidade da citrulina foi de 96,4 por cento para detectar rejeicão celular aguda (RCA) moderada ou grave. A especificidade para as complicações mais freqüentes, rejeição e infecção foi de 54 por cento-74 por cento nas crianças e 83 por cento-88 por cento nos adultos, e o valor preditivo negativo (VPN) foi > 99 por cento. CONCLUSÃO: A citrulina pode ser utilizada como método não-invasivo para avaliar a evolução do enxerto intestinal após três meses do TI. Os episódios de RCA moderado e grave podem ser afastados quando o valor da citrulina for maior que 13 µmoles/L devido ao alto valor preditivo negativo.

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

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.

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.

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.

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.

Contemporaneous chronic rejection of multiple allografts with principal pancreatic involvement in modified multivisceral transplantation.

The patient was a 10 yr-old-male with short gut syndrome secondary to Hirschsprung's disease, who underwent a modified (no liver) multivisceral transplant (stomach, pancreas, small and large intestine). The patient experienced malabsorption early in the post-operative course and had been dependent on a combination of enteral and intravenous nutrition. He developed symptoms of bowel obstruction and was suspected to have chronic rejection by an exploratory laparotomy four yr after transplant. Re-transplantation of a multivisceral transplant (stomach, pancreas, liver, small and large intestine) was performed. Microscopic examinations of the explanted allograft organ block revealed varying degrees of chronic rejection in many of the organs but with the pancreatic allograft being affected most severely. The malabsorption symptom following the first transplant may have been caused by the early onset of chronic pancreatic allograft dysfunction. Our case indicates varying severity of chronic rejection among multiple allografts where the pancreatic allograft appeared most susceptible to chronic rejection.

Gastrointestinal tract ulcers in pediatric intestinal transplantation patients: etiology and management.

One of the observed complications in patients after intestinal transplantation is the occurrence of ulcers in the native or transplanted gastrointestinal tract. Previous reports have described the appearance of ulcers but have not described any systemic approach to accurately diagnose the etiology of the ulcer. We evaluated 112 intestinal transplantation patients at our institution, in which endoscopic examination identified ulcer formation in 11 patients. No common or defining demographic or clinical variables were found in the patients with ulcers. Biopsies were obtained from the ulcer edge as well as the intervening mucosa. The most common changes in the ulcers were compatible with post-transplant lymphoproliferative disorder (PTLD), acute rejection, and viral infections. These changes could occur simultaneously and retrospective analysis showed that ulcers could have concomitant etiologies. Endoscopically directed biopsies of ulcer edges often displayed morphologic changes compatible with acute rejection of the graft. Some patients were treated for rejection based on the changes within the mucosa outside the ulcer bed, and they responded with resolution of the ulcers. Our findings demonstrate that PTLD and acute rejection are the most common causes of chronic ulcer formation and reinforce the concept that biopsy samples should be collected simultaneously from both the ulcer edge and intervening mucosa.

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.