Native Spleen Preservation During Visceral Transplantation Inhibits Graft-Versus-Host-Disease Development: Clinical and Experimental Study.

OBJECTIVE: We aimed to assess whether native spleen preservation during visceral transplantation (VT) affects graft-versus-host-disease (GVHD) incidence. SUMMARY BACKGROUND DATA: GVHD is one of the most severe and frequently lethal hematological complications after VT procedures. Because there is no specific treatment for GVHD, it is imperative to develop a strategy to reduce donor lymphocyte engraftment and proliferation. METHODS: Our study included both clinical and experimental data. A total of 108 patients were divided into 3 groups: a native spleen preservation group, a native spleen removal with no donor spleen group, and a donor spleen included (allogeneic spleen) group. We also used an allogeneic VT rat model, in which recipients were divided into 2 groups: a native spleen preservation (+SP) group and a native spleen removal (-S) group. Skin rash appearance, histopathological changes, chimerism, and spleen effects on circulating allogeneic T-cells were assessed. RESULTS: The patients with native spleen preservation showed a lower rate of GVHD ( P <.001) and better survival ( P <.05) than those in the other groups. Skin and histological signs of GVHD were lower in the rats in the +SP group ( P <.05). The donor T-cell frequency in the bloodstream and skin was also significantly reduced when the native spleen was preserved ( P <.01 and P <.0001, respectively). CONCLUSIONS: The clinical and experimental data indicate that recipient spleen preservation protects against GVHD after VT, and donor cell clearance from the bloodstream by spleen macrophages could be the underlying mechanism. Therefore, spleen preservation should be considered in VT procedures, whenever possible.

European Liver Transplant Registry: Donor and transplant surgery aspects of 16,641 liver transplantations in children.

BACKGROUND AND AIMS: The European Liver Transplant Registry (ELTR) has collected data on liver transplant procedures performed in Europe since 1968. APPROACH AND RESULTS: Over a 50-year period (1968-2017), clinical and laboratory data were collected from 133 transplant centers and analyzed retrospectively (16,641 liver transplants in 14,515 children). Data were analyzed according to three successive periods (A, before 2000; B, 2000-2009; and C, since 2010), studying donor and graft characteristics and graft outcome. The use of living donors steadily increased from A to C (A, n = 296 [7%]; B, n = 1131 [23%]; and C, n = 1985 [39%]; p = 0.0001). Overall, the 5-year graft survival rate has improved from 65% in group A to 75% in group B (p < 0.0001) and to 79% in group C (B versus C, p < 0.0001). Graft half-life was 31 years, overall; it was 41 years for children who survived the first year after transplant. The late annual graft loss rate in teenagers is higher than that in children aged <12 years and similar to that of young adults. No evidence for accelerated graft loss after age 18 years was found. CONCLUSIONS: Pediatric liver transplantation has reached a high efficacy as a cure or treatment for severe liver disease in infants and children. Grafts that survived the first year had a half-life similar to standard human half-life. Transplantation before or after puberty may be the pivot-point for lower long-term outcome in children. Further studies are necessary to revisit some old concepts regarding transplant benefit (survival time) for small children, the role of recipient pathophysiology versus graft aging, and risk at transition to adult age.

Preclinical Study of DCD and Normothermic Perfusion for Visceral Transplantation.

Considering recent clinical and experimental evidence, expectations for using DCD-derived intestines have increased considerably. However, more knowledge about DCD procedure and long-term results after intestinal transplantation (ITx) is needed. We aimed to describe in detail a DCD procedure for ITx using normothermic regional perfusion (NRP) in a preclinical model. Small bowel was obtained from pigs donors after 1 h of NRP and transplanted to the recipients. Graft Intestinal samples were obtained during the procedure and after transplantation. Ischemia-reperfusion injury (Park-Chiu score), graft rejection and transplanted intestines absorptive function were evaluated. Seven of 8 DCD procedures with NRP and ITx were successful (87.5%), with a good graft reperfusion and an excellent recovery of the recipient. The architecture of grafts was well conserved during NRP. After an initial damage of Park-chiu score of 4, all grafts recovered from ischemia-reperfusion, with no or very subtle alterations 2 days after ITx. Most recipients (71.5%) did not show signs of rejection. Only two cases demonstrated histologic signs of mild rejection 7 days after ITx. Interestingly intestinal grafts showed good absorptive capacity. The study's results support the viability of intestinal grafts from DCD using NRP, contributing more evidence for the use of DCD for ITx.

First multivisceral transplantation in Mitchell-Riley/Martinez-Frias syndrome.

BACKGROUND: MRS/MFS is a rare multisystem disorder with a poor prognosis. The high mortality rate of this syndrome is related to the severity of the associated gastrointestinal, pancreatic, and hepatobiliary conditions, as most of them are not amenable to conventional medical and surgical treatments. METHODS: We report the case of a Romani girl with all the key clinical features of MRS/MFS, and a review of cases reported in the literature. Our patient is a newborn from consanguineous parents who presented duodenal atresia, hypoplastic pancreas, gallbladder agenesis, and neonatal diabetes. Given the clinical suspicion of MRS/MFS, a genetic analysis was performed which revealed the presence of a homozygous variant in the RFX6 gene. During the course of the disease, the patient presented intractable secretory diarrhea and severe intestinal failure. RESULTS: At 2 years of age, she underwent MVT of the stomach, duodenum, small intestine, colon, liver, and pancreas. There were no surgical complications. Histologic evaluation of the small bowel showed extensive patches of gastric heterotopia. After more than 10 years of follow-up, she had presented with normal gastrointestinal, hepatic, and pancreatic function. She has one of the longest survival periods in the literature. CONCLUSIONS: Our experience suggests that multivisceral transplantation may be a promising option in select cases of MRS/MFS.

Graft infusion of adipose-derived mesenchymal stromal cells to prevent rejection in experimental intestinal transplantation: A feasibility study.

BACKGROUND: Mesenchymal stromal cells (MSC) have been proposed as a promising complement to standard immunosuppression in solid organ transplantation because of their immunomodulatory properties. The present work addresses the role of adipose-derived MSC (Ad-MSC) in an experimental model of acute rejection in small bowel transplantation (SBT). MATERIAL/METHODS: Heterotopic allogeneic SBT was performed. A single dose of 1.5x106 Ad-MSC was intra-arterially delivered just before graft reperfusion. Animals were divided into CONTROL (CTRL), CONTROL+Ad-MSC (CTRL_MSC), tacrolimus (TAC), and TAC+Ad-MSC (TAC_MSC) groups. Each Ad-MSC groups was subdivided in autologous and allogeneic third-party groups. RESULTS: Rejection rate and severity were similar in MSC-treated and untreated animals. CTRL_MSC animals showed a decrease in macrophages, T-cell (CD4, CD8, and Foxp3 subsets) and B-cell counts in the graft compared with CTRL, this decrease was attenuated in TAC_MSC animals. Pro- and anti-inflammatory cytokines and some chemokines and growth factors increased in CTRL_MSC animals, especially in the allogeneic group, whereas milder changes were seen in the TAC groups. CONCLUSION: Ad-MSC did not prevent rejection when administered just before reperfusion. However, they showed immunomodulatory effects that could be relevant for a longer-term outcome. Interference between tacrolimus and the MSC effects should be addressed in further studies.

Delayed introduction of sirolimus in paediatric intestinal transplant recipients: indications and long-term benefits.

To review our experience using sirolimus in a single centre paediatric intestinal transplantation cohort. Intestinal transplant patients with more than 3 months follow-up were divided into two groups according to their immunosuppression regimen: tacrolimus, (TAC group, n = 45 grafts) or sirolimus (SRL group, n = 38 grafts), which included those partially or completely converted from tacrolimus to sirolimus. The indications to switch were tacrolimus side effects and immunological complications. Survival and complications were retrospectively analysed comparing both groups. SRL was introduced 9 months (0 months-16.9 years) after transplant. The main cause for conversion was worsening renal function (45%), followed by haemolytic anaemia (21%) and graft-versus-host-disease (16%). Both groups showed a similar overall patient/graft survival (P = 0.76/0.08) and occurrence of rejection (24%/17%, P = 0.36). Immunological complications did not recur after conversion. Renal function significantly improved in most SRL patients. After a median follow-up of 65.17 months, 28/46 survivors were on SRL, 26 with monotherapy, with good graft function. Over one-third of our patients eventually required SRL conversion that allowed to improve their kidney function and immunological events, without entailing additional complications or survival impairment. Further trials are warranted to clarify the potential improvement of the standard tacrolimus maintenance by sirolimus conversion or addition.

Donor-Specific Antibodies in Pediatric Intestinal and Multivisceral Transplantation: The Role of Liver and Human Leukocyte Antigen Mismatching.

Rejection is one of the most important drawbacks for graft and patient survival in intestinal and multivisceral transplantation. However, there is no consensus on the diagnostic criteria for humoral rejection, and the literature about the role of donor-specific antibodies (DSA) on allograft outcome and the risk factors that contribute to their development is scant with contradictory results. The present study analyzes the role of DSA exclusively in a pediatric cohort of 43 transplants. Among our patients, 11.6% showed preformed DSA, but they did not correlate with more rejection or less allograft survival. Having previous transplants was the main sensitization factor with an odds ratio (OR) = 44.85 (P = 0.001). In total, 16.3% of recipients developed de novo donor-specific antibodies (dnDSA), mostly directed against human leukocyte antigen (HLA) class II, polyspecific and complement fixing. Additionally, the presence of dnDSA had a deleterious effect on graft rejection (hazard ratio [HR] = 11.00; P = 0.01) and survival (HR = 66.52; P < 0.001) in an observational period of 5 years after transplantation. The inclusion of the liver emerged as the main protective factor against dnDSA development with an OR = 0.07 (P = 0.007). The analysis of HLA compatibility at the serological and epitope level with the computational tools HLAMatchmaker and PIRCHE revealed no association between HLA mismatching and dnDSA. In conclusion, this study performed in pediatric recipients shows the deleterious effect of dnDSA on intestinal transplantation supported by the complement-fixing activity observed. Additionally, the liver inclusion in the allografts showed to be a protective factor against dnDSA generation.

Long-term results of surgery for bowel lengthening: how many transplants are avoided, for which patients?

PURPOSE OF REVIEW: One of the biggest successes of intestinal rehabilitation programs is that more patients achieve enteral autonomy without transplantation. Many factors are responsible of this accomplishment including new parenteral formulas, better catheter management, surgical management, and the experience of the teams. The purpose of this review is to analyze recent published papers regarding intestinal lengthening procedures trying to find out how many transplantations are avoided and for which patients. RECENT FINDINGS: A trend towards performing less intestinal transplants has been identified in the last years. The general improvement of intestinal rehabilitation accounts for this step forward. However, the role of intestinal lengthening has not been clarified. SUMMARY: Surgical techniques for autologous reconstructive surgery are not limited to bowel lengthening. Longitudinal intestinal lengthening and tailoring and serial transverse enteroplasty offered good results in terms of intestinal adaptation, long-term survival, and subsequent need of intestinal transplantation. In recent series, less than one quarter of patients who underwent intestinal lengthening required salvage intestinal transplantation.

Post-transplant lymphoproliferative disorders and other malignancies after pediatric intestinal transplantation: incidence, clinical features and outcome.

PTLDs are a well-recognized and potentially fatal complication after intestinal transplantation. We analyzed the incidence, clinical features, and outcome in a 63 intestinal transplantation series performed in our unit between October 1999 and July 2011. Types of graft included ISB (n = 23), LSB (n = 20), and MV (n = 20). Patients were categorized into three groups of immunosuppression: I (n = 43) received basiliximab, tacrolimus, and steroids; II (n = 11) thymoglobulin and tacrolimus, and III (n = 9) alemtuzumab and tacrolimus. EBV status was serially assessed. All PTLD cases were biopsied to establish histopathological diagnosis. The incidence of PTLD was 14.2% (9/63). Median onset of PTLD after transplant was four months (range: 0.5-28), within first postoperative year in 6 (66.6%) patients. Fever was the most common symptom. Graft removal was needed in four patients (44%). The patient survival rate was 66.6% (6/9). We have not found any association between PTLD and immunosuppression regimen or transplant type. However, there was a statistical association with EBV active infection.

Intussusception Management in Children: A 15-Year Experience in a Referral Center.

OBJECTIVE: To report a 15-y, single-center experience in the management and outcomes of ileocolic intussusception (ICI) episodes. METHODS: A retrospective study was performed in patients with ICI episodes, who were treated at a single quaternary referral center from 2005 to 2019. Data evaluated included patient demographics, clinical presentation, treatment modalities, hospital stay, complications, and outcomes. RESULTS: A total of 546 ICI episodes (66.1% males) were included, with a median age at diagnosis of 15 mo. Enema reduction was performed in 478 patients (87.6%), with an overall success rate of 85.8%. Hydrostatic saline enema was the most effective method (89.3%) when compared to pneumatic (80.6%) or barium enema (79.8%), this difference being statistically significant (p = 0.031). No associated complications were observed during nonoperative reduction. Surgical treatment was performed in 101 patients, in whom 36 bowel resections were performed. Postoperative complications were reported in 6 patients (5.9%). Hospital stay was significantly longer in patients with operative management (median 5 d vs. 1 d; p < 0.001). CONCLUSIONS: Nonoperative management has a high overall success rate and low complication and recurrence rates. Saline enema reduction presents the highest effectiveness, and should be considered the first-line treatment.

Neutrophil-to-Lymphocyte Ratio as a Predictor of the Need for Surgical Treatment in Children's Intussusception.

OBJECTIVE: Neutrophil-to-lymphocyte ratio (NLR) is an emerging inflammatory marker in abdominal pathologies. Ileocolic intussusception (ICI) involves a progressive intestinal inflammation, and the effectiveness of nonsurgical treatment (enema) might be related to the inflammation degree, although no previous studies have investigated this relationship. Our aim is to identify predictors of the need for surgical treatment in ICI. MATERIALS AND METHODS: A single-center, retrospective, case-control study was performed in children with ICI, who were treated with initial nonsurgical management between 2005 and 2019. Patients were divided in two groups: A (effective enema) and B (need for surgery). Admission demographic and clinical and laboratory data were analyzed. Specificity and sensitivity of the different parameters as predictors of the need for surgical treatment were determined by receiver operating characteristic (ROC) curves. RESULTS: A total of 511 patients were included (410: group A; 101: group B), without statistically significant demographic differences. Group B presented significantly higher frequency of vomiting, bloody stools, and longer median time since symptoms onset (24 vs. 8 hours; p < 0.001). Group B presented higher median laboratory inflammatory markers than group A: NLR (6.8 vs. 1.8; p < 0.001), neutrophils (10,148 vs. 7,468; p < 0.001), and C-reactive protein (CRP; 28.2 vs. 4.7; p < 0.001). In ROC curve analysis, NLR had an area under the curve of 0.925, higher than neutrophil count (0.776; p = 0.001), CRP (0.670; p = 0.001), and time since symptoms onset (0.673; p = 0.001). It was estimated a cut-off point of NLR greater than 4.52 (sensitivity: 73.2%; specificity: 94.5%). CONCLUSION: High NLR values imply a high degree of bowel inflammation and might anticipate the need for surgical treatment in ICI in children. LEVEL OF EVIDENCE: III.

Neutrophil-to-lymphocyte ratio as a predictor of surgical site infection in acute appendicitis.

Background: Surgical site infection (SSI) is one of the most common complications after appendectomy, which carries high associated morbidity. Therefore, it is essential to determine SSI predictive factors in order to prevent its occurrence. The aim of this study is to explore the role of neutrophil-to-lymphocyte ratio (NLR) as a predictor of SSI after appendectomy in children. Methods: A single-center, retrospective cohort study was performed in children who underwent appendectomy between 2017-2020. Demographics, time since symptoms onset, laboratory tests at admission, ultrasound appendiceal diameter, rate of complicated appendicitis, surgical aproach, surgery time and SSI rate were analyzed. Follow-up was performed during hospitalization and at outpatient clinic at 2 weeks and 30 days postoperatively to assess the surgical wound aspect. Diagnostic cut-off values of these markers for SSI prediction were based on the significance in the univariate analysis. Variables with a P value <0.05 in the univariate analysis were then entered into the multivariate analysis. Results: A total of 1,136 patients (710 males; 426 females) were included. SSI was reported in 53 patients (4.7%) during the 30-day follow-up after appendectomy (SSI group), with no demographic differences with the control group. Time since symptoms onset was significantly higher in SSI group (24 vs. 18 hours; P=0.034), as well as ultrasound appendiceal diameter (10.5 vs. 8.5 mm; P=0.010). Complicated appendicitis was observed in about 60% of both groups, without differences in surgical approach between them. Surgery time was statistically higher in the SSI group (62.4 vs. 47.9 min; P<0.001). SSI group presented higher counts of leukocytes, neutrophils and NLR than control group (P<0.001). NLR was the parameter with the highest area under the curve (AUC) (AUC =0.808; P<0.001), with a cut-off point of 9.8 with maximum sensitivity (77.8%) and specificity (72.7%). NLR was an independent predictive factor for SSI in the multivariate analysis [odds ratio (OR) 1.82 (1.13-2.73); P<0.01]. Conclusions: NLR value at admission was the most promising predictive factor for the development of SSI in children undergoing appendectomy. It is an easy, simple, inexpensive, and rapid method to detect patients at high risk for SSI. However, further prospective studies are still needed to confirm these results.

Mucosal appendicitis: How can it be differentiated from nonappendicitis?

OBJECTIVES: Mucosal appendicitis is defined by neutrophilic infiltration limited to the mucosa, with no transmural invasion; it is currently a controversial entity. The aim of our study was to determine whether mucosal appendicitis represents an early stage of acute appendicitis (AA) or should be considered a negative appendectomy. METHODS: A retrospective study was performed of children with suspected AA who underwent surgical treatment between 2017 and 2020. The participants were divided into 2 groups according to histologic appendiceal findings: mucosal appendicitis (MA) and negative appendicitis (NA). Demographic, clinical, ultrasound, and laboratory features were compared between the groups. RESULTS: A total of 1269 patients with suspected appendicitis in whom appendectomy was performed were included, with a median age of 10.5 years. Mucosal appendiceal inflammation was histologically confirmed in 30 cases (MA group), while no inflammation or other pathologic findings were observed in 25 cases (NA group), with no differences in demographic, clinical, or ultrasound features between the groups. Those in the MA group presented with significantly higher leukocyte and neutrophil counts and higher neutrophil to lymphocyte ratios (NLRs) than those in the NA group (P < .001). The NLR was the parameter with the highest area under the curve (0.736) for the diagnosis of MA. A cutoff of 3.20 was established, with a maximum sensitivity and specificity of 62.5% and 78.9%, respectively. CONCLUSIONS: Mucosal appendicitis presents with laboratory and histologic inflammatory features that can be distinguished from nonappendicitis and should therefore be considered a pathologic entity within the spectrum of AA. Preoperative leukocyte and neutrophil counts and NLRs may help reduce the number of negative appendectomies.

Recurrence of bile salt export pump deficiency after liver transplantation.

Severe bile salt export pump (BSEP) deficiency is a hereditary cholestatic condition that starts in infancy and leads to end-stage liver disease. Three children who underwent orthotopic liver transplantation for severe BSEP deficiency had post-transplantation episodes of cholestatic dysfunction that mimicked the original disease. Remission of all episodes was achieved by intensifying the immunosuppressive regimen. The phenotypic recurrence of the disease correlated with the presence of circulating high-titer antibodies against BSEP that inhibit transport by BSEP in vitro. When administered to rats, these antibodies targeted the bile canaliculi and impaired bile acid secretion.

Clinical and radiologic manifestations of congenital extrahepatic portosystemic shunts: a comprehensive review.

Congenital extrahepatic portosystemic shunt (CEPS) is a rare condition in which the portomesenteric blood drains into a systemic vein, bypassing the liver through a complete or partial shunt. Most often, the diagnosis is made primarily with Doppler ultrasonography. Computed tomographic angiography and magnetic resonance angiography are used for further classification of the shunt and assessment of accompanying anomalies. Conventional angiography is necessary when results of the other tests disagree or are inconclusive. CEPS is classified into two types according to the pattern of anastomoses between the portal vein and systemic vein. In type 1, intrahepatic portal venous supply is absent; in type 2, intrahepatic portal venous supply is preserved. Type 1 usually occurs in girls with associated malformations, such as situs ambiguous with polysplenia and congenital heart defects. Associated anomalies are less frequent in type 2, and symptoms usually develop later without a gender preference. Hepatic encephalopathy and liver dysfunction are possible complications of both types and usually develop during adulthood. Both types are also associated with regenerative hepatic nodules. The clinical setting and imaging appearance of these nodules can help one avoid misdiagnosis. Definitive treatment of CEPS is determined by the type of shunt. Liver transplantation is the only effective treatment for symptomatic type 1 CEPS; surgical closure or embolization of the shunt is the therapeutic approach for type 2.

Healthcare staff as promoters of parental presence at anesthetic induction: Net Promoter Score survey.

BACKGROUND: Surgical intervention is usually a traumatic event that causes stress and anxiety in the pediatric patient and the family environment. To reduce the harmful effects of presurgical anxiety, parental presence during induction of anesthesia (PPIA) is one of the more notable interventions used in medical centers. However, data on this measure are difficult to evaluate and often face resistance from healthcare staff. AIM: To analyze the perception of the healthcare workers after the implementation of a PPIA program. METHODS: A survey was developed and sent by email to all the healthcare staff working in the children's area of a tertiary hospital. It consisted of 14 items divided into positive aspects of PPIA and negative aspects of PPIA evaluated with the use of a Likert scale (1 to 5). The demographics of the respondents were included in the data collected. The answers to the questions were interpreted through the Net Promoter Score (NPS). The statistical analysis compared the differences in the responses to each question of the survey made by the different groups of health personnel included. RESULTS: A total of 141 surveys were sent out, with a response rate of 69%. Of the total number of responses, 68% were from women and 32% from men. The average age of the participants was 42.3 ± 10.6 years. As for the positive questions about the PPIA, 83% had an NPS > 50, and only one had a score between 0 and 50, which means that the quality of the service was rated as excellent or good by 100% of the respondents. On the other hand, 100% of the negative questions about the PPIA had a negative NPS. Responses to the question "PPIA increases patient safety" were significantly different (P = 0.037), with a lower percentage of pediatric surgeons (70%) thinking that PPIA increased patient safety, compared with anesthesiologists (90%), nursing (92%), and other medical personnel (96%). CONCLUSION: The personnel who participated in the PPIA program at our center were in favor of implementation. There were no validated arguments to support worker resistance to the development of the PPIA.

Routine Ultrasound Control after Successful Intussusception Reduction in Children: Is It Really Necessary?

INTRODUCTION: Recurrence of ileocolic intussusception (ICI) has been related to residual bowel wall edema after enema reduction. Early oral tolerance has been associated with a higher risk of re-intussusception, so an imaging test (ultrasound) has traditionally been performed before restarting oral tolerance. Our aim is to analyze the cost-effectiveness of performing a routine ultrasound in patients who remain asymptomatic after successful enema reduction. MATERIALS AND METHODS: A retrospective observational study was performed in patients with ICI who underwent a successful enema reduction between 2005 and 2019 and distributed in two groups according to whether or not a routine ultrasound was performed before restarting oral tolerance: group A (ultrasound) or B (no ultrasound). We analyzed demographic, clinical and laboratory variables, length of hospital stay, and recurrence rate. RESULTS: We included 366 patients who presented 373 ICI episodes (165 in group A and 208 in group B), without significant differences in gender and age. Group A patients presented a higher percentage of vomiting and bloody stools than those in group B without differences in the other clinical features studied, time of evolution, or laboratory variables. Group A presented a higher length of hospital stay than group B (36 vs. 24 hours), although it was not statistically significant (p = 0.30). No statistically significant differences were observed in the recurrence rate between both groups (10.3% A vs. 10.8% B; p = 0.83). CONCLUSION: Performing routine ultrasound before restarting oral tolerance in asymptomatic patients after successful ICI reduction does not decrease the risk of re-intussusception and should not be routinely encouraged.

Autoimmune cytopaenia after paediatric intestinal transplantation: a case series.

Autoimmune cytopaenia is a rare, but severe complication after solid organ transplantation. We retrospectively analysed 57 paediatric intestinal transplants performed in 49 patients between 1999 and 2009. Autoimmune cytopaenia was observed in six patients; it appeared after an average of 10 months post-transplant. Warm autoimmune haemolytic anaemia was developed in three patients, cold autoimmune haemolytic anaemia in one and two presented a mixed type. Incidence and causes for haematological cytopaenia such as the following were investigated: immunosuppression, major blood mismatch, viral infection, malignancy, passenger lymphocyte syndrome and lymphoproliferative disorders. Initial treatment included high-dose steroids, intravenous immunoglobulin, plasmapheresis and maintenance of body temperature above 37°C in those with cold autoantibodies. Inclusion of the spleen in multivisceral transplants seems to be an important risk factor. All patients, except one, relapsed after classic therapy, requiring additional treatments. Sirolimus conversion was performed in four patients. One died after infection. The immunosuppressive therapies associated with other concomitant factors, such as viral infections, lymphoproliferative disorders, graft-versus-host disease, passenger lymphocyte syndrome and the inclusion of the spleen as part of multivisceral graft seem to play an important part in the development of autoimmune processes after intestinal transplantation. Therapy is not well established, especially in those resistant to first-line treatment.

The use of sirolimus as a rescue therapy in pediatric intestinal transplant recipients.

To review our experience with SRL as a second-line therapy in our series of 45 SBTx recipients (1997-2009). Retrospective review of five children converted to SRL: 3 M/2 F; median of three yr old (range 20 months-18 yr); rescue indications, adverse events with SRL, resolution of tacrolimus-related side effects, incidence of rejection, PTLD, or GVHD were summarized. Tacrolimus was discontinued (average 13 months after transplant) because of refractory hemolytic anemia in four patients with decreased renal function and because of advanced renal failure and unclear neutropenia in one. PTLD and GVHD had been previously diagnosed in two. Tacrolimus-related side effects disappeared in all five although other immunosuppressants and splenectomy were used simultaneously or later in most of them. Adverse events reported after the conversion were infections (tuberculosis and Pneumocystis carinii in two) and mild hypertriglyceridemia. No rejection, GVHD, or PTLD episode was observed. Four patients are alive with excellent quality of life (median follow-up 18 months). Sirolimus is a safe rescue therapy in SBTx children when tacrolimus is not well tolerated. Renal function and hematologic disorders seem to improve, although other simultaneous strategies could be also involved. Further studies could demonstrate its efficacy as a first-line treatment.