-
[show abstract]
[hide abstract]
ABSTRACT: To date, no child has been reported to develop de novo CCA after liver transplantation although patients with transplants have a significantly higher risk of malignancy than the general population. CCA is extremely rare in the pediatric age group, seen mostly in patients with a history of choledochal cysts, Caroli's disease, or PSC. We report the first case of pediatric de novo CCA in the liver allograft 12 yr after liver transplantation.
Pediatric Transplantation 08/2009; 14(8):E110-4. · 1.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Detection of PTLD uses PCR to detect circulating EBV DNA in the blood or in situ hybridization to identify EBV DNA in tissue biopsies. EBV DNA was detected in the tissue section using both real-time PCR and in situ hybridization. We report an unusual presentation of PTLD with no detectable EBV DNA in the blood using EBER-1 and EBNA-1 PCR assays. This report suggests that the use of EBV-PCR for the early detection of PTLD in blood samples may not be 100% effective in detecting disease.
Pediatric Transplantation 06/2008; 13(1):134-8. · 1.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
Pediatric Transplantation 04/2006; 10(2):162-7. · 1.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Severe gastrointestinal dysmotility (GID) impairs patients' quality of life and is almost uniformly fatal after complications of parenteral nutrition. Intestinal and multivisceral transplants have been used as alternative treatment of these disorders. We studied patients with GID treated with transplantation in our center, and reviewed their outcome to determine the therapeutic efficacy of multivisceral transplants.
The transplant database was searched for patients with GID from 1994 to 2001. We excluded patients with Hirschsprung disease, scleroderma, and diabetic enteropathy. We reviewed explanted organs, histochemistry, and immunohistochemistry and classified cases by etiology.
We selected 12 children with GID from 124 patients transplanted. Nine presented before 1 year and 3 started with symptoms between 2 and 8 years. By combined clinical and histopathological features, 6 were classified as megacystis microcolon intestinal hypoperistalsis syndrome, 4 as chronic idiopathic intestinal pseudoobstruction, and 2 as intestinal neuronal dysplasias. Six patients died during the follow-up from 21 to 546 days after transplant. The Kaplan-Meier actuarial survival rates were 66.7% at 1 year and 50% at 3 years.
Multivisceral transplantation is a valuable therapeutic alternative for children with severe GID who cannot be adequately managed with parenteral nutrition.
Journal of Pediatric Surgery 11/2005; 40(10):1598-604. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Primary wound closure is not always possible after pediatric multi-visceral transplantation because of oversized donor organs and/or intestinal or graft edema. We report our experience evaluating the safety and efficacy of Graftskin (Apligraf, Organogenesis, Canton, Mass), a bioengineered bi-layered human skin equivalent, for the management of difficult skin abdominal defects after multivisceral transplantation in a pediatric population.
A retrospective chart review was performed of pediatric multivisceral transplantation patients who were treated with Graftskin. Adverse events, course of wound reepithelialization, and time for complete closure were recorded.
Four patients, 7 to 29 months old, were treated with Graftskin. One patient died because of unrelated reasons. Stimulation of the granulation, reepithelialization, and rapid reduction of the wound surface and depth occurred in the other 3 patients. Complete reepithelialization occurred within 5 months. No adverse events were noted.
Graftskin was a successful treatment for difficult abdominal skin defects after liver and multivisceral transplantation in children.
Journal of the American Academy of Dermatology 06/2005; 52(5):854-8. · 3.99 Impact Factor
-
Tomoaki Kato,
Jeffrey J Gaynor,
Genarro Selvaggi, Naveen Mittal,
John Thompson,
Gwenn E McLaughlin,
Seigo Nishida,
Jang Moon,
David Levi,
Juan Madariaga,
Phillip Ruiz,
Andreas Tzakis
[show abstract]
[hide abstract]
ABSTRACT: We performed 124 intestinal transplants on 108 children (median age, 1.5 years) since 1994. Initial graft types included isolated intestine (I) (n=26), liver and intestine (LI) (n=26), multivisceral (MV) (n=50), and multivisceral without liver (MMV) (n=6). Four groups were defined by type of induction therapy: none, OKT3, or cyclophosphamide (August 1994-December 1997, n=25), early experience with daclizumab (January 1998-December 2000, n=26), recent experience with daclizumab (January 2001-April 2004, n=40), and Campath-1H (January 2001-April 2004, n=17). Actuarial patient survival at 1 year for groups 1-4 was 44%+/-10%, 54%+/-10%, 83%+/-6%, and 41%+/-12%, respectively, with group 3 having the most favorable survival (P=0.0004). Using Cox stepwise regression, the hazard rate of developing severe rejection was significantly higher in patients with transplant type I or LI (P=0.0002), with no difference between these groups (P=0.24) but a significantly higher rate for LI versus MV (P=0.005). Three factors associated with improved patient survival were recipient of MV or MMV (P=0.008), age at transplantation greater than 1 year (P=0.01), and use of daclizumab (P=0.0006). Cause-specific hazard analysis revealed a decreased rate of rejection-related mortality for recipients of MV or MMV (P=0.0007), whereas age greater than 1 year indicated a lower rate of infection-related mortality (P=0.0009). Pediatric intestinal transplantation provides an increasingly realistic chance of survival, particularly with the more recent use of daclizumab and multivisceral transplantation. A protective effect of multivisceral transplantation appears to exist with respect to the development of severe rejection.
Journal of Gastrointestinal Surgery 02/2005; 9(1):75-89; discussion 89. · 2.83 Impact Factor
-
Peter A Pappas,
Andreas G Tzakis,
Jeffrey J Gaynor,
Manuel R Carreno,
Phillip Ruiz,
Frans Huijing,
Gary Kleiner,
Daniel Rabier,
Tomoaki Kato,
David M Levi,
Seigo Nishida,
Barry Gelman,
John F Thompson, Naveen Mittal,
Jean-Marie Saudubray
[show abstract]
[hide abstract]
ABSTRACT: Small preliminary studies suggest that serum citrulline levels may act as a marker for acute cellular rejection in small intestinal transplant recipients. The results comparing serum citrulline concentrations with biopsy-based grades of rejection are summarized here for an expanded group of 26 isolated intestinal and multivisceral transplant recipients. Other factors considered included patient and donor age and sex, ischemia time, serum creatinine, and type of transplant. Straight-line fits reasonably described how each patient's citrulline levels changed over time. Among 21 patients who demonstrated increasing citrulline levels over time, the estimated median time-to-achieve normal citrulline (>or=30 micromol/L) was 79 days post-transplant. Using stepwise linear regression, two characteristics were associated with a significantly higher maximum grade of rejection after 14 d post-transplant: longer time-to-achieve normal citrulline (using ranks, p < 0.00001) and the patient not receiving a multivisceral transplant (p = 0.0005). Only the latter characteristic was significantly associated with maximum grade of rejection during the first 14 d post-transplant (p = 0.01). Clearly, time-to-normalization of citrulline was delayed by the incidence of rejection, and in some cases with moderate-to-severe rejection, normalization of citrulline levels never occurred. We plan to further examine the use of citrulline as a marker for rejection in larger prospective studies.
American Journal of Transplantation 07/2004; 4(7):1124-32. · 6.39 Impact Factor
-
Andreas G Tzakis,
Panagiotis Tryphonopoulos,
Werviston De Faria,
Tomoaki Kato,
Seigo Nishida,
David M Levi,
Juan Madariaga,
Debbie Weppler, Naveen Mittal,
Phillip Ruiz,
Jose R Nevy,
John F Thompson
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
Journal of the American College of Surgeons 12/2003; 197(5):770-6. · 4.55 Impact Factor
-
Andreas G Tzakis,
Tomoaki Kato,
Seigo Nishida,
David M Levi,
Juan R Madariaga,
Jose R Nery, Naveen Mittal,
Arie Regev,
Patricia Cantwell,
Anthony Gyamfi,
Debbie Weppler,
Joshua Miller,
Panagiotis Tryphonopoulos,
Phillip Ruiz
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
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.
Transplantation 05/2003; 75(8):1227-31. · 4.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the incidence of adenovirus (AdV) infection in pediatric liver and intestinal transplant recipients, the records of patients with possible AdV infection were reviewed for demographic data, symptomatology, methods of diagnosis, treatment and outcome. To evaluate the impact of polymerase chain reaction (PCR) amplification and identification of AdV DNA as a diagnostic test, the incidence and outcome of AdV before and after the introduction of PCR were compared. Adenovirus infection was identified in 4.1% of liver recipients and 20.8% of intestinal transplant recipients. The overall incidence of AdV did not increase over time, even following the introduction of PCR for virus detection. The higher incidence of AdV in the pediatric intestinal transplant recipients may be attributed to the frequent application of PCR methodology to intestinal biopsy material. Detection of AdV by PCR was associated with reduced mortality compared with detection by culture, either because of earlier detection of invasive disease or because PCR detects the presence of latent as well as active AdV.
American Journal of Transplantation 03/2003; 3(2):224-8. · 6.39 Impact Factor
-
Tomoaki Kato, Naveen Mittal,
Seigo Nishida,
David Levi,
Noriyo Yamashiki,
Barbara Miller,
Monica Gonzalez,
Phillip Ruiz,
Juan Madariaga,
Jose Nery,
Barry Gelman,
John Thompson,
Anthony Gyamfi,
Andreas Tzakis
[show abstract]
[hide abstract]
ABSTRACT: Modern neonatal care, surgical treatment, and total parenteral nutrition (TPN) have improved survival rate for babies with extensive gut resections. The authors examined the role of intestinal transplantation in the treatment of these patients.
The authors reviewed all pediatric intestinal transplants performed for short bowel syndrome at our center (70 transplants performed between Aug 1994 and Feb 2002). Factors affecting patient survival were analyzed.
Older patient age at the time of transplant was a significant factor favorably affecting patient survival (P =.031). Trends toward better survival rates were observed in those transplants performed more recently (P =.063), in those patients with greater body weight (P =.084), in those not hospitalized at the time of transplant (P =.14), and in those without concomitant liver failure (P =.12). Three-year survival rate for patients greater than age 2 years and without liver failure was 90%. However, 32% of our recipients underwent transplant at age less than one year, and most in this group (75%) had concomitant liver failure.
For babies with irreversible intestinal failure, intestinal transplantation is a life-saving option. Results, which have recently improved, are best when transplantation compliments more conservative surgical treatments and TPN. However, there is a subset of patients who have liver disease early requiring urgent transplant.
Journal of Pediatric Surgery 03/2003; 38(2):145-9. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the incidence of adenovirus (AdV) infection in pediatric liver and intestinal transplant recipients, the records of patients with possible AdV infection were reviewed for demographic data, symptomatology, methods of diagnosis, treatment and outcome. To evaluate the impact of polymerase chain reaction (PCR) amplification and identification of AdV DNA as a diagnostic test, the incidence and outcome of AdV before and after the introduction of PCR were compared. Adenovirus infection was identified in 4.1% of liver recipients and 20.8% of intestinal transplant recipients. The overall incidence of AdV did not increase over time, even following the introduction of PCR for virus detection. The higher incidence of AdV in the pediatric intestinal transplant recipients may be attributed to the frequent application of PCR methodology to intestinal biopsy material. Detection of AdV by PCR was associated with reduced mortality compared with detection by culture, either because of earlier detection of invasive disease or because PCR detects the presence of latent as well as active AdV.
American Journal of Transplantation 02/2003; 3(2):224 - 228. · 6.39 Impact Factor
-
Phillip Ruiz,
Monica Garcia,
Peter Pappas,
Thierry Berney,
Violet Esquenazi,
Tomoaki Kato, Naveen Mittal,
Deborah Weppler,
David Levi,
Seigo Nishida,
Jose Nery,
Joshua Miller,
Andreas Tzakis
[show abstract]
[hide abstract]
ABSTRACT: Acute vascular rejection (AVR) in human small-bowel transplantation is an inadequately characterized entity whose frequency and severity is not well understood. As compared to severe AVR, changes identifying early, mild or evolving AVR are not known. We created a scoring system to evaluate subtle mucosal vascular changes and examined 188 biopsies from 21 patients obtained in the first 3 months post transplant. A majority of patients had a transient rise in vascular injury, often within 30 days of transplant. Small-vessel congestion and erythrocyte extravasation were the most common alterations. The vascular injury score was not related to acute cellular rejection, HLA type or HLA antigen disparities. However, the patients with the vascular changes had significantly higher peak panel reactive antibodies (PRA) and a higher incidence of positive T-cell and B-cell crossmatch. Finally, graft survival was significantly lower in the patients demonstrating the early vascular lesions. These data suggest that the vascular injury is partially associated with humoral presensitization of the recipient and may be a form of acute vascular rejection. Since these vascular changes are frequent, we advocate early post-transplant monitoring to identify and manage potentially high-risk patients.
American Journal of Transplantation 02/2003; 3(1):43-9. · 6.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Necrotizing fasciitis is a rare, subcutaneous infection. It can occur in patients after solid-organ transplantation. We herein report two patients who developed necrotizing fasciitis following combined liver and small intestine transplantation. The first patient experienced this infection 4 yr after transplantation and 1 yr after the closure of the ileostomy. The second patient suffered from necrotizing fasciitis 2 days after the transplant. Both cases were diagnosed on the physical findings, culture of subcutaneous lavage, and the computed tomography findings. The site of entrance of the organism was not clear in either case. Both patients had a fulminant course and died within 1 week from the onset, despite aggressive surgical intervention. Therefore, necrotizing fasciitis has to be recognized as a potential complication of intestinal transplantation.
Pediatric Transplantation 10/2002; 6(4):344 - 347. · 1.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Necrotizing fasciitis is a rare, subcutaneous infection. It can occur in patients after solid-organ transplantation. We herein report two patients who developed necrotizing fasciitis following combined liver and small intestine transplantation. The first patient experienced this infection 4 yr after transplantation and 1 yr after the closure of the ileostomy. The second patient suffered from necrotizing fasciitis 2 days after the transplant. Both cases were diagnosed on the physical findings, culture of subcutaneous lavage, and the computed tomography findings. The site of entrance of the organism was not clear in either case. Both patients had a fulminant course and died within 1 week from the onset, despite aggressive surgical intervention. Therefore, necrotizing fasciitis has to be recognized as a potential complication of intestinal transplantation.
Pediatric Transplantation 09/2002; 6(4):344-7. · 1.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
Transplantation 03/2002; 73(4):555-9. · 4.00 Impact Factor
-
Pediatric Transplantation 12/2001; 5(2):75 - 79. · 1.48 Impact Factor
-
Peter A. Pappas,
Jean-Marie Saudubray,
Andreas G. Tzakis,
Daniel Rabier,
Manuel R. Carreno,
Orlando Gomez-Marin,
Frans Huijing,
Barry Gelman,
David M. Levi,
Jose R. Nery,
Tomoaki Kato, Naveen Mittal,
Seigo Nishida,
John F. Thompson,
Phillip Ruiz
[show abstract]
[hide abstract]
ABSTRACT: Background. There is no known serum marker for intestinal rejection. Serum concentrations of the amino acid citrulline arise almost exclusively from the intestinal mucosa. We examined the impact of acute cellular rejection (ACR) of intestinal allografts on serum citrulline levels.
Methods. Citrulline concentrations were assayed in serum samples of healthy volunteers (n=6) and seven patients who underwent small bowel transplants (SBTx). Trends in mean citrulline concentrations versus degree of ACR were assessed by matching posttransplantation citrulline concentrations with patients' grade of ACR at time of serum collection. Rejection was confirmed by biopsy and graded by following standardized criteria. An additional patient had citrulline concentrations determined for 31 sequential specimens 3-60 days posttransplant.
Results. Mean citrulline concentrations in controls were significantly higher than posttransplantation samples at any rejection grade. Mean concentrations declined significantly as rejection severity increased. The overall downward trend was statistically significant (P <0.05). In sequential measurements, citrulline levels increased significantly over time with declining severity of rejection. The increase in mean citrulline concentration between posttransplant days 3-16 and 52-60 was significant (P <0.01).
Conclusions. Serum citrulline levels decline with increasing grade of ACR and may be a useful serum marker for intestinal rejection.
Transplantation 10/2001; 72(7):1212-1216. · 4.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Intestinal failure requiring total parenteral nutrition (TPN) is associated with significant morbidity and mortality. Intestinal transplantation can be a lifesaving option for patients with intestinal failure who develop serious TPN-related complications. The aim of this study was to evaluate survival, surgical technique, and patient care in patients treated with intestinal transplantation. We reviewed data collected from 95 consecutive intestinal transplants performed between December 1994 and November 2000 at the University of Miami. Fifty-four of the patients undergoing intestinal transplantation were children and 41 were adults. The series includes 49 male and 46 female patients. The causes of intestinal failure included mesenteric venous thrombosis (n = 12), necrotizing enterocolitis (n = 11), gastroschisis (n = 11), midgut volvulus (n = 9), desmoid tumor (n = 8), intestinal atresia (n = 6), trauma (n = 5), Hirschsprung's disease (n = 5), Crohn's disease (n = 5), intestinal pseudoobstruction (n = 4), and others (n = 19). The procedures performed included 27 isolated intestine transplants, 28 combined liver and intestine transplants, and 40 multivisceral transplants. Since 1998, we have been using daclizumab (Zenepax) for induction of immunosuppression and zoom videoendoscopy for graft surveillance. We began to use intense cytomegalovirus prophylaxis and systemic drainage of the portal vein. The 1-year patient survival rates for isolated intestinal, liver and intestinal, and multivisceral transplantations were 75%, 40%, and 48%, respectively. Since 1998, the 1-year patient and graft survival rates for isolated intestinal transplants have been 84% and 72%, respectively. The causes of death were as follows: sepsis after rejection (n = 14), respiratory failure (n = 8), sepsis (n = 6), multiple organ failure (n = 4), arterial graft infection (n = 3), aspergillosis (n = 2), post-transplantation lymphoproliferative disease (n = 2), intracranial hemorrhage (n = 2), and fungemia, chronic rejection, graft vs. host disease, necrotizing enterocolitis, pancreatitis, pulmonary embolism, and viral encephalitis (n = 1 case of each). Intestinal transplantation can be a lifesaving alternative for patients with intestinal failure. The prognosis after intestinal transplantation is better when it is performed before the onset of liver failure. Rejection monitoring with zoom videoendoscopy and new immunosuppressive therapy with sirolimus, daclizumab, and campath-1H have contributed to the improvement in patient survival.
Journal of Gastrointestinal Surgery 6(2):233-9. · 2.83 Impact Factor
