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.     

Intestinal transplantation for total intestinal aganglionosis: a series of 12 consecutive children

Background

Management of patients with total intestinal aganglionosis (TIA) is a medical challenge because of their dependency on parenteral nutrition (PN). Intestinal transplantation (ITx) represents the only alternative treatment for patients with irreversible intestinal failure for achieving intestinal autonomy.

Methods

Among 66 patients who underwent ITx in our center, 12 had TIA. They received either isolated ITx (n = 4) or liver-ITx (LITx, n = 8) after 10 to 144 months of total PN. All grafts included the right colon.

Results

After a median follow-up of 57 months, the survival rate was 62.5% in the LITx group and 100% in the ITx patients. The graft survival rate was 62.5% in the LITx group and 75% in the ITx group. All the surviving patients were fully weaned from total PN, after a median of 57 days. Pull through of the colon allograft was carried out in all patients. Fecal continence is normal in all but one of the surviving children.

Conclusion

These results suggest that ITx with colon grafting should be the preferred therapeutic option in TIA. Early referral to a transplantation center after diagnosis of TIA is critical to prevent PN-related cirrhosis and thereby to permit ITx, which is associated with a good survival rate.     

Isolated intestinal transplants vs. liver-intestinal transplants in adult patients in the United States: 22 yr of OPTN data

We examined the outcomes of adult intestinal transplants (ITx); isolated ITx vs. liver-intestinal transplants (L-ITx) were compared using the UNOS database (1987-2009). Of 759 ITx transplants in 687 patients, 463 (61%) were isolated and 296 (39%) were L-ITx. Patient survival for primary isolated ITx at one, three, and five yr was 84%, 66.7%, and 54.2%; and primary L-ITx was, 67%, 53.3%, and 46% (p = 0.0005). Primary isolated ITx graft survival at one, three, and five yr was 80.7%, 57.6%, 42.8%; primary L-ITx was 64.1%, 51%, 44.1% (p = 0.0003 at one, three yr, Wilcoxon test). For retransplants (n = 72), patient and graft survival for isolated ITx (n = 41) at five yr was 40% in era 1 (1987-2000) and 16% in era 2 (p = 0.47); for retransplanted L-ITx (n = 31), it improved from 14% to 64% in era 2 (p = 0.01). Cox regression: creatinine >1.3 mg/dL and pre-transplant hospitalization were negative predictors for outcome of both; bilirubin >1.3 mg/dL was a negative predictor for isolated ITx and donor age >40 yr for L-ITx. Isolated ITx should be considered prior to liver disease for adults with intestinal failure; L-ITx is preferable for retransplantation.     

Italian guidelines for intestinal transplantation: potential candidates among the adult patients managed by a medical referral center for chronic intestinal failure

In 2002, the Italian guidelines for eligibility of patients for intestinal transplantation (ITx) were defined as: life-threatening complications of home parenteral nutrition (HPN), lack of venous access for HPN, locally invasive tumors of the abdomen, Chronic intestinal failure (CIF) with a high risk of mortality, primary disease-related poor quality of life (QoL) despite optimal HPN. Our aim was to identify potential candidates for ITx according to these national guidelines among patients managed by a medical referral center for CIF. Records of patients who received HPN were reviewed. CIF was considered reversible or irreversible (energy by HPN <50% or >50% basal energy expenditure). Patients with irreversible CIF were considered eligible for ITx in the absence of a contraindication, as are used for solid organs Tx. From 1986 to 2003 among 64 patients who met the entry criteria 23 showed reversible and 41 irreversible, CIF. Twenty-one patients with irreversible CIF had an indication for ITx, but eight had also contraindications; thus 13 were eligible, including intestinal pseudo-obstruction (n = 6), mesenteric ischemia (n = 3), Crohn's (n = 2), radiation enteritis (n = 1), and desmoid (n = 1). Indications for ITx included HPN liver failure (n = 2), lack of venous access (n = 2), CIF with high risk of mortality (n = 3), very poor QoL (n = 6 including 5 with pseudo-obstruction). According to the Italian guidelines for ITx, 31% of patients with irreversible CIF managed by a medical referral center were eligible for ITx. Primary disease-related poor QoL was the indication in half of them. Studies on the QoL after ITx are required to allow patients to make an educated decision.     

Surgical complications after intestinal transplantation in infants and children—UK experience

Surgical complications have a significant impact on morbidity and mortality following intestinal transplantation (ITx). Birmingham Children's Hospital commenced intestinal transplantation in 1993 and the following surgical strategies evolved: (a) pretransplant abdominal tissue expanders, 1998; (b) combined en-bloc reduced liver and intestinal transplantation (CRLITx), 1998; (c) staged abdominal closure, 2001; (d) preservation of graft duodenal artery, 2005.

Aim

An internal audit was performed to document the surgical complications after ITx and to evaluate strategies in the management and prevention of complications.

Methods

A retrospective analysis of the medical records from January 1993 to June 2007 was conducted to identify surgical complications, evaluate management strategies, and report outcome following ITx.

Results

Forty-six children underwent 49 ITx (9 isolated intestinal, 39 combined liver and intestinal [CLITx], and 1 multivisceral transplant). Twenty three children had CRLITx since 1998, although there were none before 1997. The median donor: recipient weight ratio in CLITx was 2.2:1 (range, 0.67:1-6.70:1). Twenty-six children experienced 29 (59%) surgical complications: portacaval shunt thrombosis (n = 2, none alive); graft duodenal stump leakage (n = 3, 2 alive); spontaneous bowel perforation(n = 6, 2 alive); sub-acute bowel obstruction (n = 6, all alive); abdominal compartment syndrome ([ACS], n = 4, 2 alive); pancreatic leak (n = 3, 2 alive); biliary complications (n = 22, 17 alive ) failed staged abdominal closure with wound sepsis requiring skin grafting into the bowel (n = 1, alive), wound dehiscence (n = 1, alive), anastomotic leak (n = 1, alive) and intra-abdominal bleeding (n = 1,alive), primary nonfunction (n = 1, 1 died). Following the complications of ACS in children with primary abdominal closure and graft duodenal stump leaks in 2004, we modified our strategies in 2005 to include staged abdominal closure with recipient to donor weight mismatch, and preservation of the gastroduodenal artery during donor organ procurement in addition to pre transplant abdominal tissue expansion. Fifteen children with recipient and donor weight mismatch subsequently required staged closure of the abdomen and none of them developed ACS. Twelve children had gastroduodenal artery preserved and none developed graft duodenal stump leaks. Twenty-four of the 46 (52%) are alive 6 months to 10 years post transplant.

Conclusion

Evolving strategies may avoid or reduce surgical complications commonly seen after intestinal transplantation and thus contribute to an improved outcome.     

Bacteremia after intestinal transplantation in children correlates temporally with rejection or gastrointestinal lymphoproliferative disease

BACKGROUND: Bacteremia occurs frequently after intestinal transplantation (ITx) in children. During our initial experience with this procedure, we noted that bacteremic episodes tended to occur simultaneously with the presence of rejection and/or gastrointestinal (GI) posttransplant lymphoproliferative disease (PTLD). AIM: To document the association of bacteremia with rejection and GI PTLD in pediatric ITx recipients. METHODS: Retrospective analysis of all medical records from 62 children who underwent ITx between July 1990 and January 1998 at Children's Hospital of Pittsburgh. A bacteremic episode was defined as two positive blood cultures from different sites at the same time or from the same site at different times. Rejection and PTLD were defined using previously published criteria. RESULTS: A total of 39/62 ITx recipients had 133 blood stream infections (2.1 episodes/patient) including 121 episodes of bacteremia and 12 of fungemia. Enteric organisms were the most frequently recovered pathogens (Gram negative rods, n=76; enterococci, n=36). Enteric organisms were recovered as a single organism (n=57), with another enteric bacteria (n=23), or with coagulase negative staphylococci (CONS) (n=24). CONS were recovered as a single organism on 21 occasions. An obvious source of bacteremia was not found for 115/121 episodes. Endoscopy was performed for 107 of the 115 bacteremia episodes; an abnormal histology was identified in 74 revealing rejection (n=36), GI PTLD (n=21), or both (n=17). When endoscopy showed GI pathology, enteric organisms alone or in combination with CONS were recovered on 63/107 occasions, although CONS were recovered alone only 11 times. CONCLUSIONS: Bacteremia accompanies GI rejection and intestinal PTLD in ITx recipients. Endoscopy should be performed to inspect the allograft when bacteremia occurs without an obvious source in these patients. This is especially true for patients with bacteremia due to enteric organisms.     

Incidence of graft rejection in small bowel transplanted pigs after immunosuppression withdrawal

As intestinal grafts require heavy immunosuppression, there are no reports of immunosuppression withdrawal after clinical small bowel transplantation. In this large-animal study, we investigated the occurrence of graft rejection in intestinal-transplanted pigs after withdrawal. Large-White unrelated piglets were transplanted and divided in three groups: group 1 (n = 5), intestinal transplantation (ITx) with no immunosuppression; group 2 (n = 7), Itx and 60 days of treatment with tacrolimus and mycophenolate mofetil; group 3 (n = 5), Itx and donor bone marrow infusion (DBMi) and 60 days of treatment with tacrolimus and mycophenolate mofetil. Follow-up time after withdrawal was 120 days. Group 1 pigs died of graft acute cellular rejection (ACR) after a median of 11 days. In group 2, two pigs died of ACR-related infection and another two of ACR within 90 days. The remaining three animals (43%) were sacrificed at day 180, and their grafts showed no signs of ACR. In group 3, two pigs died of ACR-related infection and one of graft versus host disease within 80 days; at day 180 the two surviving animals showed signs of chronic rejection in the allograft. This study demonstrates that total withdrawal after ITx is followed by sudden and lethal ACR (or ACR-related infection) in more than 50% of the recipients. When a tolerance-inducing strategy as DBMi is applied, lethal graft versus host disease may also occur. In group 3, the intestinal allograft, to which the recipients were partially tolerant, developed chronic rejection that was probably associated with a decline with time of donor-leukocytes chimerism, as recently demonstrated in rats.     

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).     

Effects of different serum-levels of ATG after unrelated donor umbilical cord blood transplantation

We determined total rabbit-IgG (r-ATG) levels in serum samples before (day 0) and after (day 11 and day 25) unrelated donor umbilical cord blood transplantation (UCBT). Most patients (27/41) suffered from a haematological malignancy. There were 25 children and 16 adults. All patients received rabbit anti-thymocyte globulin (ATG) at a total dose of 6 or 8mg/kg as part of the conditioning. No correlation between the dose of ATG and serum r-ATG levels post UCBT was found. The cumulative incidence of acute GVHD grades III-IV in patients given the 6 and 8mg/kg ATG dose was 15% and 13% (ns), respectively. Patients with r-ATG≤40μg/mL 11days after UCBT (n=19) had a higher incidence of grades III-IV acute GVHD (32% vs. 0%, p<0.01), higher TRM (69% vs. 7%, p=0.005), less relapse (17% vs. 82%, p<0.01) but similar relapse-free survival (RFS) (10% vs. 18%, p=0.4) compared to those with r-ATG>40μg/mL (n=17). Low serum-levels of r-ATG early after transplantation seem to be a strong predictor for acute GVHD grades III-IV, TRM and a low incidence of relapse in patients treated with thymoglobulin before unrelated donor UCBT.     

Impact of induction therapy on bacterial infections and long-term outcome in adult intestinal and multivisceral transplantation: a comparison of two different induction protocols: daclizumab vs. alemtuzumab

Abstract: Introduction: Induction therapy with daclizumab or alemtuzumab has been recently introduced for intestinal transplantation; however, the impact of such induction therapy on bacterial infections remains to be clarified. The purpose of this study was to evaluate the impact of induction therapy on the incidence of bacterial infections and long‐term patient survival. Patients and methods: Over the past seven yr, we performed 39 intestinal (ITx) and multivisceral (MTVx) transplants in 38 adult patients. In the early period, daclizumab was used for induction, and tacrolimus and steroids were administered for maintenance [daclizumab and tacrolimus (DT) group; n = 11]. From 2002, we used alemtuzumab for induction, with low‐dose tacrolimus maintenance [alemtuzumab and tacrolimus (AT) group; n = 23]. The incidence of bacterial infections and patient outcome were compared between the two groups. Results: There were no significant differences in recipient and donor demographics, procedure (ITx vs. MTVx), and cold and warm ischemic time between the two groups. Within 30 d after ITx, bacterial infections were observed in seven patients (64%) in the DT and in 14 patients (64%) in the AT group. Between 30 and 180 d after ITx, a total of 17 episodes of bacterial infections were observed in the DT and 26 episodes in the AT group. Three patients in the DT and eight in the AT group died, and all of the deaths were related to infectious complications except one each in DT and AT. Conclusion: There was no difference in incidence of bacterial infections and long‐term patient survival between the two groups.     

Alloimmune Myositis as Paraneoplastic Complication of an Oral Squamous Cell Carcinoma After Severe Chronic Graft vs Host Disease or a Manifestation of Chronic Graft vs Host Disease? A Case Report and Literature Discussion

A 53-year-old female patient with acute myeloid leukemia developed severe chronic graft vs host disease (cGVHD) of the oral mucosa after allogeneic hematopoietic stem cell transplantation with leukoplakia and relapsing oral squamous cell carcinoma (SCC) of the tongue. cGVHD needed long-lasting immunosuppressive therapy; SCC was treated with radiation and surgery. Acute myeloid leukemia remained in complete remission. The patient developed a myositis with pain of all muscles as well as paraparesis with elevated creatine kinase and C-reactive protein and detection of antiskeletal muscle autoantibodies 3500 days after hematopoietic stem cell transplantation. No other clinical features of chronic GVHD were apparent at this time. Symptoms disappeared after treatment with corticosteroids but relapsed while tapering. Weekly therapy with the B-cell-depleting antibody rituximab was started and administered for 6 weeks. Symptoms disappeared again but partly returned after some weeks, so therapy with azathioprine was started. During therapy with azathioprine slow tapering of corticosteroids was possible and clinical symptoms remained absent. Here we present a case report and review of the literature on alloimmune myositis as paraneoplastic complication of an oral SCC of the tongue after severe chronic GVHD or as late manifestation of chronic GVHD itself.     

Intestinal Transplantation for Chronic Intestinal Pseudo-Obstruction in Adult Patients

Intestinal transplantation (ITx) has become a life-saving procedure for patients with irreversible intestinal failure who can no longer be maintained on parenteral nutrition (PN). This report presents the results of our experience on ITx in patients suffering from chronic intestinal pseudo-obstruction (CIPO). Between December 30, 2000 and May 30, 2003 six adult patients affected by CIPO underwent primary ITx at our Center. Pre-transplant evaluation, indication for ITx and surgical technique are reported. On December 30 2003, the mean follow-up was 25.0 months. No peri-operative deaths occurred in the study population and five out of six patients are alive, with 1-year patient and graft survival of 83.3% and 66.6%. Although our series is limited by the number of patients, our experience suggests that ITx transplantation should be considered in adult patients suffering from CIPO and PN life-threatening complication.     

Clinical characteristics and outcomes of PTLD following intestinal transplantation

Post‐transplant lymphoproliferative disease (PTLD) has the highest incidence following intestinal transplantation (ITx). Our center has seen a recent increase in PTLD. Our aim was to review a single‐center PTLD experience with a focus on clinical characteristics and outcomes. We completed a retrospective review of biopsy‐proven PTLD cases using a prospectively maintained database of 115 ITx recipients transplanted between 1991 and 2014. Nineteen (17%) ITx recipients developed 25 PTLD cases during a median follow‐up time of 6.4 (1.6‐14.6) years. The incidence of early PTLD was 6% (n = 7). There was a trend toward increased risk of PTLD in children compared with adults (P = .11) and a significantly increased risk of PTLD in re‐ITx compared with primary ITx recipients (P = .03). Most PTLD cases were diagnosed between 2010 and 2014 (n = 14). All early PTLD cases were EBV+ on in situ hybridization. Overall graft and patient survival are 68% and 74%, respectively. Second episodes of PTLD were diagnosed in 43% of surviving pediatric patients. Our program has a low incidence of early PTLD with overall excellent graft and patient survival following diagnosis. However, we have also seen a rising incidence of late PTLD. The cause of the increase is unknown as no major changes in immunosuppression protocols have occurred since 1999.     

Anti-TNF-alpha therapy for acute rejection in intestinal transplantation

INTRODUCTION: We present our experience with infliximab rescue therapy for steroid- and OKT3-resistant rejection after intestinal transplantation (ITx). METHODS: Twelve ITx and one multivisceral transplant recipients were immunosuppressed with tacrolimus, rapamycin, daclizumab, steroids (n = 10) or tacrolimus, campath, and steroids (n = 3). RESULTS: In two patients, severe acute rejection did not resolve despite steroid bolus therapy plus 5 to 10 days of OKT3 treatment. Signs of moderate rejection persisted in the distal portions of the grafts. Treatment with infliximab, a chimeric anti-TNF-alpha antibody (four infusions of 3 mg/kg body weight), induced a complete remission of histological and clinical signs of rejection. Two further patients with steroid-resistant rejection received two courses of infliximab (3 mg/kg body weight) as antirejection therapy. All rejection episodes resolved completely. CONCLUSIONS: Infliximab effectively treats steroid and OKT3 resistant acute rejection episodes of intestinal transplantations.     

Surgical approach to short-bowel syndrome. Experience in a population of 160 patients.

OBJECTIVE: The authors reviewed their experience with short-bowel syndrome to define the surgical approach to this problem in 160 patients. METHODS: Forty-eight adults and 112 children were evaluated over a 15-year period. RESULTS: Seventy-one patients (44%) adapted to resection and took enteral nutrition alone. Forty-four patients (28%) were supported by parenteral nutrition (PN). Forty-five patients (28%) have had 49 surgical procedures. Fifteen patients with adequate intestinal length (> 120 cm in adults) but dilated dysfunctional bowel underwent stricturoplasty (n = 4) or tapering (n = 11). Thirteen patients (87%) demonstrated clinical improvement. Fourteen patients with shorter remnants (90-120 cm) and rapid transit time received an artificial valve (n = 2) or a reversed segment (n = 1). All patients' conditions improved initially, but the reversed segment was revised or taken down. Fourteen patients with short remnants and dilated bowel underwent intestinal lengthening. Twelve patients' conditions improved (86%), one underwent transplantation, and one died. Sixteen patients with very short remnants (< 60 cm) and complications of PN underwent solitary intestine (n = 4) or combined liver-intestinal transplantation (n = 13). One-year graft survival was 65%. There have been five deaths. CONCLUSIONS: The surgical approach to short-bowel syndrome depends on the patient's age, remnant length and caliber, intestinal function, and PN-related complications. Nontransplant procedures have a role in the treatment of selected patients. Intestinal transplantation is emerging as a potential therapy for patients with significant PN-related complications.     

Intestinal Transplantation under Tacrolimus Monotherapy after Perioperative Lymphoid Depletion with Rabbit Anti-Thymocyte Globulin (Thymoglobulin®)

Modifications in the timing and dosage of immunosuppression can ameliorate the morbidity and mortality that has prevented widespread use of intestinal transplantation (ITx) in children. Thirty-six patients receiving ITx, aged 5 months to 20 years were given 2-3 mg(kg of rabbit anti-thymocyte globulin (rATG, thymoglobulin) just before ITx, and 2-3 mg(kg postoperatively (total 5 mg(kg). Twice daily doses of tacrolimus (TAC) were begun enterally within 24 h after graft reperfusion with reduction of dose quantity or frequency after 3 months. Prednisone or other agents were given to treat breakthrough rejection. After 8-28 months follow-up (mean 15.8 +/- 5.3), 1- and 2-year patient and graft survival is 100% and 94%, respectively. Despite a 44% incidence of acute rejection in the first month, 16 of the 34 (47%) survivors are on TAC (n = 14) or sirolimus (n = 2) monotherapy; 15 receive TAC plus low dose prednisone; one each receive TAC plus sirolimus, TAC plus azathioprine and TAC plus sirolimus and prednisone. There was a low incidence of immunosuppression-related complications. This strategy of immunosuppression minimized maintenance TAC exposure, facilitated the long-term control of rejection, decreased the incidence of opportunistic infections, and resulted in a high rate of patient and graft survival.     

Risk factors for acute graft-versus-host disease in histocompatible donor bone marrow transplantation

We have analyzed factors associated with acute graft-versus-host disease following allogeneic bone marrow transplantation in 469 patients with histocompatible sibling donors between 1979 and 1987. Overall, 46 +/- 5% (95% confidence interval) developed clinical grade II-IV acute GVHD following transplantation. In univariate analysis, patient or donor age greater than or equal to 18 years was significantly associated with increased GVHD risks (greater than or equal to 18, 63 +/- 6% grade II-IV GVHD vs. less than 18, 27 +/- 6%, P less than .0001), without incremental risk in older adults. Univariate analysis showed that donor:recipient sex match and female:female transplants were associated with less-frequent GVHD. More frequent GVHD was associated with chronic myelogenous leukemia, cytomegalovirus seropositivity, and prior donor alloimmunity (pregnancy or transfusion). Additionally, the allele HLA-A26 was associated with increased risk of GVHD (72%, P = .005) while HLA-DR3 was associated with less GVHD (31%, P = .03). Stepwise multivariate analysis confirmed the increased GVHD risks associated with older recipient age, HLA-A26 and donor:recipient gender (not female:female) and the protective effect of HLA-DR3. Similar results were found using the different analytic technique of recursive partition analysis, which identified within the adult population the lowest GVHD risk in female recipients with nonalloimmunized female donors (20%), while other gender combinations had 68% acute GVHD, regardless of donor alloimmunity. In children (less than 18 years), lower GVHD risk accompanied donor:recipient sex-matched (18%) versus mismatched (33%) BMT. Clinical trials undertaken to lessen the hazards of GVHD must be designed with appropriate attention to these reproducibly identified clinical variables associated with different GVHD risks.     

Small intestine transplantation in the rat--immunology and function

Heterotopic, vascularized small intestine transplants were performed in inbred strains of rats to investigate the structural, functional, and immunologic consequences of intestinal transplantation with and without immunosuppression with cyclosporine (CyA). Lewis X Brown Norway F1 intestine was rejected by untreated Lewis recipients in 7 to 10 days. Structurally, rejected intestine was characterized by shortened crypts and villi lined by damaged attenuated epithelial cells. Functionally, rejection was associated with impaired epithelial active ion transport as indicated by decreased potential difference and with diminished epithelial barrier function as reflected by decreased transepithelial resistance. Administration of CyA for 7 days prevented clinical rejection and partially prevented the structural and functional defects. Lewis intestine transplanted into Lewis X Brown Norway F1 recipients caused fatal graft versus host disease (GVHD) in 9 to 17 days. Treatment with CyA for 7 days failed to prevent GVHD routinely, but prolonged administration delayed fatal GVHD until CyA was discontinued. Intestine from Lewis "B" rats made deficient of T cells by thymectomy, irradiation, and reconstitution with syngeneic T cell-depleted bone marrow failed to cause GVHD in Lewis recipients. Reconstitution of the "B" rats with T cells before transplantation restored the GVHD response. These results may be relevant in the consideration of clinical small intestinal transplantation.     

Impact of positive preoperative surveillance blood cultures from chronic indwelling catheters in cadaveric intestinal transplant recipients

Recurrent bloodstream infections are a common indication for intestinal transplantation (ITx). Often, clinical symptoms may be absent in the setting of bacteremia, especially in patients with chronic liver disease. This study investigated the incidence and impact of positive blood cultures (BCx) obtained from central venous catheters used for total parenteral nutrition (TPN) in asymptomatic patients immediately prior to cadaveric ITx. Of 13 consecutive patients transplanted between November 2003 and November 2004, 12 underwent preoperative surveillance BCx with four positives (33%). Isolates included Staphylococcus epidermidis (n = 2), methicillin-resistant Staphylococcus aureus, and Citrobacter freundii. All four patients with positive BCx displayed liver dysfunction at the time of transplant (> or = grade 2 fibrosis, total bilirubin >8.0 g/dL), three of whom were inpatients. In contrast, only three of eight nonbacteremic patients showed liver disease of comparable severity. Liver dysfunction and inpatient status at the time of transplant appear to predict positive blood cultures. Postoperative length of stay and time on the ventilator were significantly longer among bacteremic as compared with nonbacteremic patients, but there were no differences in intraoperative blood use, time to total parenteral nutrition independence, or operative time between bacteremic and nonbacteremic patients. Our study showed that occult bacteremia in asymptomatic pre-intestinal transplant patients was not uncommon and may increase postoperative morbidity. Preemptive removal of long-term central venous catheters should be considered prior to ITx.     

Outcome of Intestinal Transplants for Patients With Crohn's Disease

Background

The pathophysiology of Crohn's disease (CD) is related to immune dysregulation making it unique among indications for intestinal transplants (ITx). We examined whether outcomes of ITx for CD are any worse than the overall ITx population.

Methods

United Network for Organ Sharing Standard Transplant Analysis and Research files were analyzed. Adult ITx recipients from 1987 to 2009 were included.

Results

Of 86 primary ITx for CD, 61 (70%) had isolated ITx and 25 (30%) had liver-ITx (L-ITx). The 1-, 3-, and 5-year patient survival for isolated ITx was 85%, 67%, and 54%; for L-ITx, 63%, 47%, and 41% (P = .04). The graft survival at 1, 3, and 5 years was 85%, 55%, and 45% for isolated ITx recipients and 63%, 47%, and 41% for L-ITx recipients (Wilcoxon's test, P = .04). Patient and graft survival was better in era 2 (January 2001 through August 2009) than in era 1 (October 1987 through December 2000). In the regression analysis of long-term outcome of adults undergoing ITx, recipient age > 40 years and hospitalization prior to transplantation were negative predictors of outcome.

Conclusion

Patient and graft survival for CD patients is not inferior to other indications for ITx.