Results of intestinal and multivisceral transplantation in adult patients: Italian experience

PURPOSE: We report our experience with intestinal and multivisceral transplantation in Italy. METHODS: We performed 23 adult isolated intestinal transplants and seven multivisceral ones, three with liver, between December 2000 and June 2005. Indications for transplantation were loss of venous access (n = 14), recurrent sepsis (n = 10), and electrolyte-fluid imbalance (n = 6), 14 of whom also presented with total parenteral nutrition (TPN)-related liver dysfunction. Immunosuppression was based on induction agents like daclizumab (followed by tacrolimus and steroids) in the first period; alemtuzumab or thymoglobulin (with tacrolimus) in a second period after 2002. RESULTS: The mean follow-up was 742 +/- 550 days. Three-year patient actuarial survival rate was 88% for intestinal transplants and 42% for multivisceral (P = .015). Three-year graft actuarial survival rate was 73% for intestinal patients and 42.8% for multivisceral (P = .1). Graft loss was mainly due to rejection (57%). Complications were mainly represented by bacterial infections (92% of patients), relaparotomies (82%), and rejections (72%). Full bowel function without any parenteral nutrition or intravenous fluid support was achieved in 60% of recipients with functioning bowel including 95% on a regular diet. One patient underwent abdominal wall transplantation as well. DISCUSSION AND CONCLUSION: Intestinal transplantation has achieved high rates of patient and graft survival with even longer follow-up. Early referral of patients, especially in cases of TPN-liver disease, is mandatory to obtain good outcomes and avoid high mortality rates on the transplant waiting list. Immunosuppressive management remains the key factor to increase the success rate.     

Ninety-five cases of intestinal transplantation at the university of Miami

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. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Georgia, May 20–23, 2001 (oral presentation).     

Twenty-seven consecutive intestinal and multivisceral transplants in adult patients: a 4-year clinical experience

Adult isolated intestinal and multivisceral transplantation is gaining acceptance as the standard treatment for patients with intestinal failure with life-threatening parenteral nutrition-related complications. We report our 4-year experience with intestinal and multivisceral transplantation. We performed 20 isolated small bowel and seven multivisceral ones, including three with liver. The underlying diseases were mainly short bowel syndrome due to intestinal infarction, chronic intestinal pseudo-obstruction, and Gardner syndrome. Indications for transplant were loss of central venous access in 14 patients, recurrent sepsis in eight patients, and major electrolyte and fluid imbalance in five patients. One-year patient actuarial survival rate was 94% for isolated intestinal transplants and 42% for multivisceral recipients (P = .003), while 1-year graft actuarial survival rate was 88.4% for isolated small bowel patients and 42.8% for multivisceral ones (P = .01). The death rate was 18.5%. Our graftectomy rate was 14.8%. Our immunosuppressive protocols were based on induction agents such as alemtuzumab, daclizumab, and antithymocyte globulins. The majority of our complications were bacterial infections, followed by rejections and relaparotomies; most rejection episodes were treated with steroid boluses and tapering. We believe that our results were due to optimal candidate and donor selection, short ischemia time, and use of induction therapy. Multivisceral transplantation is a more complex procedure with less frequent clinical indications than isolated small bowel transplant, but our data concerning multivisceral transplants include only a small number of patients and require further evaluation.     

Intestinal and multivisceral transplantation after abdominal trauma

SUMMARY: BACKGROUND Some trauma victims who survive acute illness develop lingering, debilitating syndromes that are incompatible with any semblance of normalcy. Intestinal failure, in particular, exacts a high price in terms of quality of life. Total parenteral nutrition (TPN) has served these patients well, but complications limit its long-term therapeutic effect. Consequently, transplantation is emerging as a life-saving therapy for some patients with the short gut syndrome.METHODS We reviewed eight adult and two pediatric recipients of intestinal and multivisceral transplants after severe abdominal trauma. Background demographics, type of abdominal trauma, transplant procedure, postoperative complications, and survival rates were appraised. This group was also compared with 47 nontrauma recipients of intestinal transplants performed during the same period.RESULTS Four patients (40%) died postoperatively (postoperative days 7, 53, 87, and 91) as a result of multiple organ failure after graft pancreatitis (n = 1), viral encephalitis (n = 1), and sepsis after severe rejection (n = 2). Six patients (60%) are alive (postoperative days 52-1,783). All are off TPN. The 4-year patient survival was 58%, with no significant difference between trauma and nontrauma patients.CONCLUSION Intestinal and multivisceral transplantation are viable options for the treatment of irreversible intestinal failure associated with severe trauma. Surviving patients are TPN independent and have a satisfactory quality of life.     

Three-year experience in clinical intestinal transplantation

BACKGROUND: The purpose of this study was to evaluate the outcome of 19 patients who underwent intestinal transplantation (ITx) for intestinal failure. METHODS: The 19 patients who underwent primary ITx between December 2000 and May 2003 were prescribed three different immunosuppressive protocols that included daclizumab, alemtuzumab, and antithymocyte globulin induction, respectively. A mucosal surveillance protocol for early detection of rejection consisted of zoom video endoscopy and serial biopsies associated with orthogonal polarization spectral imaging. Retrospective review of the clinical records was performed to assess the impact of new modalities of immunosuppression and intestinal mucosal monitoring on patient outcomes. RESULTS: All patients were adults (mean age 35.8 years). Etiology of intestinal failure included chronic intestinal pseudo-obstruction (n = 6), intestinal angiomatosis (n = 1), Gardner syndrome (n = 2), intestinal infarction (n = 8), radiation enteritis (n = 1), and intestinal atresia (n = 1). All patients experienced complications from total parenteral nutrition (TPN). Thirteen patients (68.4%) received isolated small bowel, whereas six (31.6%) received multivisceral grafts with or without the liver. Thirteen of 19 patients experienced at least one episode of rejection (68.4%). Most ACR episodes were treated with steroid boluses and resolved completely within 5 days. The overall 1-year patient survival was 82%. All living patients are in good health with functioning grafts having been weaned off TPN after a mean of 23.7 days post-ITx. DISCUSSION: Advances in immunosuppressive therapy with early detection and prompt treatment of rejection episodes make ITx a valuable treatment option for patients with intestinal failure and TPN-related life-threatening complications.     

Twenty‐eight years of intestinal transplantation in Paris: experience of the oldest European center

Our aim was to describe our achievements in pediatric intestinal transplantation (ITx) and define areas for improvement. After a period (1987–1990) of nine isolated small bowel transplants (SBTx) where only one patient survived with her graft, 110 ITx were performed on 101 children from 1994 to 2014: 60 SBTx, 45 liver–small bowel, four multivisceral (three with kidneys), and one modified multivisceral. Indications were short bowel syndrome (36), motility disorders (30), congenital enteropathies (34), and others (1). Induction treatment was introduced in 2000. Patient/graft survival with a liver‐containing graft or SBTx was, respectively, 60/41% and 46/11% at 18 years. Recently, graft survival at 5/10 years was 44% and 31% for liver‐containing graft and 57% and 44% for SBTx. Late graft loss occurred in 13 patients, and 7 of 10 retransplanted patients died. The main causes of death and graft loss were sepsis and rejection. Among the 55 currently living patients, 21 had a liver‐containing graft, 19 a SBTx (17 after induction), and 15 were on parenteral nutrition. ITx remains a difficult procedure, and retransplantation even more so. Over the long term, graft loss was due to rejection, over‐immunosuppression was not a significant problem. Multicenter studies on immunosuppression and microbiota are urgently needed.     

Intestinal transplantation in children: differences between isolated intestinal and composite grafts

The results of the isolated intestinal grafts were compared with those of composite grafts (intestinal graft + liver) in a series of 18 transplantations performed in 17 children; 5 isolated intestinal grafts, 12 hepatointestinal grafts, and 1 multivisceral graft. Causes of intestinal failure were short bowel syndrome (n = 13), motility disorders (n = 2) and congenital epithelial disorders (n = 2). Transplantation was indicated due to end-stage liver disease (n = 14), loss of venous access (n = 2), untreatable diarrhea (n = 1) and high morbidity associated with a poor quality of life (n = 1). Six children, all with a composite graft, died after transplantation due to lymphoma (n = 2), sepsis (n = 1); intraabdominal bleeding (n = 1); pneumonia (n = 1); and overwhelming adenoviral infection (n = 1). Digestive autonomy was achieved in 16 of 18 grafts, the 11 surviving children are free of parenteral nutrition with a reasonably good quality of life. In conclusion, intestinal transplantation is a viable therapeutic alternative for children with permanent intestinal failure. The results of transplantation with an isolated intestine are clearly better that those with a composite graft.     

Intestinal transplantation: 1997 report of the international registry. Intestinal Transplant Registry

BACKGROUND: Small bowel transplantation is an evolving procedure. We reviewed the world experience since 1985 to determine the current status of this procedure. METHODS: All of the known intestinal transplant programs were invited to contribute to an international registry using a standardized report form. RESULTS: Thirty-three intestinal transplant programs provided data on 273 transplants in 260 patients who were transplanted on or before February 28, 1997. The number of procedures per year has increased at a linear rate since 1990, with 58 transplants performed in 1996. Two-thirds of the recipients were children or teenagers. The short gut syndrome was the most common indication for transplantation. The types of transplants included the small bowel with or without the colon (41%); the intestine and liver (48%); and multivisceral grafts (11%). The 1-year graft/patient survival for transplants performed after February 1995 was 55%/69% for intestinal grafts; 63%/66% for small bowel and liver grafts; and 63%/63% for multivisceral grafts. Transplants since 1991 and programs that had performed at least 10 transplants had significantly higher graft survival rates. Seventy-seven percent of the current survivors had stopped total parenteral nutrition (TPN) and resumed oral nutrition. CONCLUSIONS: Transplantation has become a lifesaving procedure for (1) patients with intestinal failure who cannot be maintained on total parenteral nutrution and (2) patients who require abdominal evisceration to completely remove locally aggressive tumors. The 5-year survival rate of intestinal transplantation with large series is comparable to lung transplantation.     

Intestinal transplantation for the treatment of desmoid tumors associated with familial adenomatous polyposis

BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis (FAP) are locally invasive. Often occurring in the mesentery of the intestine, they sometimes recur after resection. Complications can include intestinal failure and dependence on parenteral nutrition. We describe 9 patients who underwent intestinal transplantation for the treatment of desmoid tumors associated with FAP. METHODS: Records of patients undergoing intestinal transplantation for desmoid tumors at 2 transplant centers were reviewed for patient age, sex, type of graft, procedure date, tumor site, desmoid complications, medications, extracolonic manifestations, status at follow-up, and length of survival. RESULTS: Nine patients with FAP and intestinal failure caused by desmoid tumors were treated with isolated intestinal (n = 6), multivisceral (n = 2), or combined liver-intestinal transplantation (n = 1). Desmoid tumors recurred in the abdominal walls of 2 patients. Two patients died: one as a result of sepsis, the other because of a rupture of a mycotic aneurysm of the aortic anastomosis. One graft lost to severe rejection was replaced with a second intestinal graft. Eleven to 53 months after transplantation, 7 patients were alive, well, independent of parenteral treatment, and leading apparently normal lifestyles. CONCLUSIONS: Transplantation of the intestine alone or as part of a multivisceral transplantation may help rescue otherwise untreatable patients with complicated desmoid tumors.     

Intestinal and multivisceral transplantation

Intestinal and multivisceral transplantation can be a lifesaving treatment for patients with complications from the treatment of intestinal failure. However, the indications for this highly specialized treatment are broadening and include other such indications as patients with acute abdominal vascular catastrophes as well as patients with previously unresectable benign intra-abdominal tumours. Since the first successful multivisceral transplant in the late 1980s, the field has expanded and more than 4000 transplants have taken place worldwide and outcomes continue to improve. However, complications are still commonplace and multivisceral and intestinal transplant recipients are more likely to suffer from the complications of transplantation than any other solid organ transplant group. The most important complications are rejection and sepsis, with sepsis remaining the leading cause of death in this patient group. That said the outcomes for intestine alone transplants have improved to such a degree that they are close to that of intestinal failure patients on long-term parenteral nutrition and therefore we may be entering an era where intestinal transplantation will be offered as an alternative to parenteral nutrition for patients with intestinal failure.     

Twenty-five consecutive isolated intestinal transplants in adult patients: a five-yr clinical experience

PATIENTS AND METHODS: Between December 2000 and December 2005, 25 isolated intestinal transplants from cadaveric donors have been performed for short gut syndrome (short bowel syndrome, 52%), chronic intestinal pseudo-obstruction (24%), Gardner syndrome (16%), radiation enteritis (4%) and massive intestinal angiomatosis (4%). Indications for transplantation were: loss of venous access, recurrent sepsis due to central line infection, major electrolyte and fluid imbalance. Liver dysfunction was present in 13 cases. All patients were adult; median age was 36.3 yr and mean weight at transplantation 61.6 kg. All recipients were on life-threatening parenteral nutrition for a mean time of 23.7 months. Mean donor/recipient body weight ratio was 1.08. Rejection monitoring was accomplished by graft ileoendoscopies and intestinal biopsies through the temporary ileostomy. Our immunosuppressive regimen was based on induction therapy with three different protocols: daclizumab for induction, tacrolimus and steroids as maintenance therapy; alemtuzumab for induction and low-dose tacrolimus as maintenance; thymoglobulin for induction and maintenance based on low-dose tacrolimus. Closure of the abdomen at the end of transplantation represented a technical problem with several options performed: graft reduction, only skin closure, prothesic meshes, abdominal closure in two steps, cutaneous flaps and abdominal wall transplant in one case. RESULTS: The mean hospital stay was 37 days. The mean follow-up 27 months. Twenty patients are alive (80%) with two- and five-yr patient survival rate of 80% and 66%; mortality rate was 20% due to sepsis in all cases. Our two- and five-yr graft survival rate is 76% and 64%, graftectomy rate was 16%. Sixteen grafts are working properly, with no need of parenteral nutrition. We diagnosed 35 mild acute cellular rejection (ACRs), seven moderate ACRs and three severe ACRs (two needed graftectomy). We experienced two episodes of chronic rejection biopsy-proven. Rapamicine was added in case of renal failure or biopsy-proven intestinal rejection. Graft-vs.-host disease was not seen in our series while post-transplant lymphoproliferative disease in two cases. After discharge, the most common indication for medical support was dehydration. The abdominal wall transplant did not experience any rejection. DISCUSSION AND CONCLUSIONS: Induction therapy has reduced the amount of postoperative immunosuppressive agents, especially in the first period, lowering the risk of renal failure and sepsis and the mucosal surveillance protocol for early detection of rejection dramatically reduced the number of severe ACR.     

Analysis of rejection episodes in over 100 pediatric intestinal transplant recipients

Rejection after intestinal transplant is a significant source of morbidity and mortality. We analyzed number of rejections, severity, and duration of episodes in pediatric recipients of intestinal transplants. One hundred eighteen intestinal transplants were performed: intestine (n = 27), liver-intestine (n = 27), modified multivisceral (n = 7), and multivisceral (n = 57). A total of 186 rejections were classified: mild (n = 89), moderate (n = 70), severe (n = 27). Duration of episodes doubled for each increasing step in severity. Treatment of mild rejection was with steroids, moderate rejection was treated with OKT3, severe rejection required OKT3 and organ removal. Most rejections occurred during the first month posttransplant, with the incidence of all rejections declining after 6 months posttransplant. Intestine and liver-intestine recipients had significantly higher probability of developing severe rejections, as compared to MVT. In summary, recipients of MVT seemed to be protected from rejection as compared to intestine or liver-intestine recipients.     

Pediatric intestinal transplantation at Packard Children's Hospital/Stanford University Medical Center: report of a four-year experience

We report a 4-year experience of a new program in pediatric intestinal transplantation. Among 50 children referred for evaluation, 27 were listed for transplantation. Two children originally listed for combined liver/small bowel transplant were changed to isolated intestinal transplant as rehabilitation efforts resulted in full recovery of hepatic function. Eighteen children received 18 grafts: 12 liver/intestine, 5 isolated intestine, and 1 multivisceral. Mean age at transplant was 3.6 year with 75% of patients aged 0 to 2 years. Five listed children died while waiting and four were still on the list. Immunotherapy included antithymocyte globulin induction and tacrolimus, sirolimus, and prednisone maintenance. At 1 year, patient and graft survivals were 75% and 67%, respectively. For isolated intestine, 1 year survivals were 100% and 75%, while for combined liver/intestine, they were 71% for both. Enteral autonomy is 100% with total parenteral nutrition stopping by 35.8 days (mean). We had two patients develop posttransplant lymphoproliferative disorder and three, exfoliative rejection, one of whom recovered completely. In conclusion, our program in pediatric intestinal transplantation has become well established with a high proportion of smaller/younger children receiving grafts. Outcomes achieved levels expected based on The Intestinal Transplant Registry and UNOS criteria, which were better than expected for isolated intestinal transplants and achievement of enteral autonomy.     

Temporary elevation of serum transaminases after pediatric intestinal transplantation: incidence and clinical correlation in multivisceral transplant vs isolated intestinal transplant

Data were gathered from the records of 51 children of median age 1.5 years who survived more than 6 months after intestinal transplantation. Abnormal liver function tests (LFTs) were defined as serum aspartate aminotransferase (AST) greater than 100 IU/L or total bilirubin greater than 2.0 g/dL lasting more than 3 days. Temporary elevation was defined when LFTs returned to normal without graft loss or death. LFT elevation at the time of transplantation was not included as a temporary LFT elevation. Median follow-up was 36 months. In multivisceral transplant recipients, all patients (n = 34) showed abnormal LFTs at transplantation that normalized within a median period of 2 days. Temporary LFT elevations were seen in 20 of 34 (59%) in multivisceral transplantation and 5 of 17 (29%) in isolated intestinal transplantation. Median length of elevation was 14 days in multivisceral transplantation and 12 days in isolated intestinal transplantation. Peak AST was 353 +/- 190 IU/dL in multivisceral transplantation and 839 +/- 605 IU/dL in isolated intestinal transplantation (P = .0059). Events associated with temporary LFT elevations in multivisceral transplantation were total parental nutrition (TPN) (n = 8), dehydration (n = 2), viral infection (n = 2), others (n = 3), and nonspecific (n = 5). Events in isolated intestinal transplantation were posttransplant lymphoproliferative disorder (n = 2), TPN (n = 1), and nonspecific (n = 2). Temporary LFT elevations were commonly seen among pediatric intestinal recipients, which correlated with events other than rejection. Approximately half of the temporary LFT elevations were associated with no significant clinical events. They resolved spontaneously. Interestingly, the peak AST value was higher in isolated intestinal transplantation compared to multivisceral transplantation.     

Outcome analysis of 71 clinical intestinal transplantations.

OBJECTIVE: The aim of the study was to determine risk factors associated with graft failure and mortality after transplantation of the intestine alone or as part of an organ complex. SUMMARY BACKGROUND DATA: Even with modern immunosuppressive therapies, clinical intestinal transplantation remains a difficult and unreliable procedure. Causes for this and solutions are needed. METHODS: Between May 1990 and February 1995, 71 intestinal transplantations were performed in 66 patients using tacrolimus and low-dose steroids. The first 63 patients, all but one treated 1 to 5 years ago, received either isolated grafts (n = 22), liver and intestinal grafts (n = 30), or multivisceral grafts (n = 11). Three more recipients of allografts who recently underwent surgery and one undergoing retransplantation were given unaltered donor bone marrow cells perioperatively as a biologic adjuvant. RESULTS: Of the first 63 recipients, 32 are alive: 28 have functioning primary grafts and 4 have resumed total parenteral nutrition after graft enterectomy. Thirty-five primary grafts were lost to technical and management errors (n = 10), rejection (n = 6), and infection (n = 19). Regression analysis revealed that duration of surgery, positive donor cytomegalovirus (CMV) serology, inclusion of graft colon, OKT3 use, steroid recycle, and high tacrolimus blood levels contributed to graft loss. All four intestine and bone marrow recipients are alive for 2-3 months without evidence of graft-versus-host disease. CONCLUSION: To improve outcome after intestinal transplantation with previous management protocols, it will be necessary to avoid predictably difficult patients, CMV seropositive donors, and inclusion of the graft colon. Bone marrow transplantation may further improve outcome by ameliorating the biologic barriers of rejection and infection and allowing less restrictive selection criteria.     

Acute cellular rejection monitoring after intestinal transplant: utility of serologic markers and zoom videoendoscopy as support of conventional biopsy and clinical findings

Acute cellular rejection (ACR) episodes in intestinal transplant recipients are diagnosed by histologic and clinical findings. We have applied zoom video endoscopy and the use of serologic markers granzyme B (GrB) and perforin (PrF) to monitor rejection together with conventional tools. Seven hundred eighty-two blood samples (obtained at the time of the biopsy) collected from 34 recipients for GrB/PrF upregulation were positive among 64.9% of ACRs during a 3-year follow-up. Considering only the first year results posttransplantation, it reached 73.1% of rejection events. Zoom videoendoscopy was used by our group in 29 recipients of isolated intestine (n = 24) or multivisceral transplantations (n = 5) to enable observation of villi and crypt areas. From more than 270 procedures, 84% of the zoom findings agreed with the histologic results, namely, a specificity of 95%. In fact, during ongoing ACR, villi were altered in 80% of cases. Both procedures were helpful to support conventional histologic findings and clinical symptoms of ACR in intestinal transplant recipients.     

Recovery from liver dysfunction after adult isolated intestinal transplantation without liver grafting

PURPOSE: We sought to evaluate liver function recovery after isolated intestinal transplantation in adults with irreversible intestinal failure. PATIENTS AND METHODS: Over a 5-year period, we transplanted 34 adult patients, 25 of whom received an isolated intestinal graft, 4 a multivisceral graft without a liver, and 5, a multivisceral graft with a liver. Among the group of patients transplanted with the isolated graft we selected 14 recipients with pretransplant liver dysfunction, namely, a serum bilirubin >2 mg/dL (normal value: 1.2) and/or transaminases >100 IU/mL (NV, 37/40). Other inclusion criteria were total parenteral nutrition, period > 3 months, no diagnosis of portal hypertension or cirrhosis. Two patients had biopsy-proven liver fibrosis. RESULTS: At discharge, all patients recovered liver function to normal values: mean bilirubin blood level was 0.9 +/- 0.96 mg/dL (range: 0.3-1.6) and mean transaminases were 26 +/- 9 and 31 +/- 18 IU/mL (range: 10-44/27-65). After a mean follow-up of 2 years, only one patient has an elevated alanine aminotransferase level without clinical signs of liver disease. Type of pretransplant liver disease did not impact on survival rates. CONCLUSION: In selected cases, an isolated intestinal or a multivisceral graft without a liver can represent a "liver salvage therapy" for an early failing liver in patients with irreversible intestinal failure. Pretransplant liver disease is not a negative prognostic factor.     

Growth after intestinal transplant in children

Intestinal transplantation has been more frequent in children with intestinal failure. However, the growth after intestinal transplantation has not been well documented. The demographics, transplant information, postoperative complications, heights, and weights were obtained retrospectively from medical records on 23 children who underwent intestinal transplantation. Z-scores were calculated from the STAT Growth-BP, based on Centers for Disease Control and Prevention growth chart (2000). Transplantations were performed between 1999 and 2004. Patient median age was 1.1 years (range 0.5 to 6.9 years). Twelve were boys and 11 girls. Seventeen children received multivisceral transplantations, one modified multivisceral transplantation, and five isolated intestinal transplantations. Baseline immunosuppression consisted of tacrolimus and corticosteroids. Daclizumab was used as induction agent in 18 patients; alemtuzumab, in five patients. Median pretransplant Z-scores were median -1.67 (n = 23) in weight, and median -3.36 (n = 21) in height. Pretransplant growth was significantly retarded. We analyzed significantly retarded patients with Z-score <-2.0. The change of weight Z-score from pretransplant was: 1.25 at 6 months (n = 11), 1.46 at 12 months (n = 10), and 2.21 at 24 months (n = 7). The change of height Z-score: 1.9 at 6 months (n = 16), 1.42 at 12 months (n = 13), and 1.51 at 24 months (n = 10). Z-score significantly improved (P < .002, ANOVA). Among the analyzed factors sex, age at transplant, length of stay, and rejection within 6 months, were not associated with catch-up growth. Children with retarded growth showed significant catch-up after successful intestinal transplantation.     

Intestinal transplantation in children: A summary of clinical outcomes and prognostic factors in 108 patients from a single center

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. Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 (oral presentation).     

Current status of intestinal transplantation in Japan

The development of total parenteral nutrition (TPN) has dramatically improved the prognosis of patients afflicted with intestinal failure. However, TPN-related complications, which remain a problem for patients with intestinal failure can be addressed by intestinal transplantation, which can significantly improve their prognosis and quality of life. The first intestinal transplantation in Japan occurred in 1996. Of the 17 intestinal transplantations performed to date, six were obtained from deceased donors and 11 from living donors. The primary indications were: short gut syndrome (n = 8), intestinal function disorder (n = 7), and retransplantation (n = 2). In our experience, the 1-year and 5-year patient survival rates are 87% and 69%. All nine patients receiving transplants in the last 7 years have survived, which seem to be acceptable results for the treatment of intestinal failure. Relatively few intestinal transplantations have been performed to date, mainly due to the lack of national health insurance coverage for the procedure and the ban of the use of donors below 15 years of age. Liver failure patients are also ineligible because liver-intestine or multiorgan transplants are not allowed by current guidelines. Case numbers may increase in the future as the result of allowing for pediatric donors in the new Act on Organ Transplantation, which went into effect in July 2010. We continue to work on reforming national insurance coverage to cover multiorgan transplantations.