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Background/purpose: Obesity has become a major public health priority. Because of disappointing results obtained with dietary and medical programs, bariatric surgery has been offered to adolescents, although this practice remains controversial. Our aim was to evaluate laparoscopic adjustable gastric banding (LAGB) in adolescents at 2-year follow-up., Material and Methods: This prospective study, from 2008 to 2013, compared results between adolescent patients and young adult controls. The LAGB technique and the follow-up program were similar. Weight loss and comorbid disease were analyzed., Results: Thirty-six adolescents (mean age at surgery=16.7±1.3years) were operated on and compared to 53 young adults (mean age at surgery=21.7±1.9years). The mean weight and BMI at surgery were 124.4±20.7 and 43.9±5.5kg/m(2), respectively. Among the adolescents, none were diabetic or hypertensive. The mean glycated hemoglobin was 5.6±1.2%. In four cases (11%) dyslipidemia was observed. There was no significant difference between the two groups in terms of initial preoperative weight or BMI. The absolute BMI values at 6, 12 and 24months after surgery were comparable between adolescents and young adults: 38.7 vs 39.8, 36.0 vs 37.6 and 33.5 vs 36.1kg/m(2), respectively. The excess weight loss was higher in adolescents at 12 and 24months: 48.6 vs 37.6% (p=0.03); and 62.3 vs 45.5% (p=0.02). During this period, insulin resistance and dyslipidemia decreased similarly in both groups., Conclusion: Provided there is careful selection of patients and a supportive multidisciplinary team, satisfying results can be obtained after LAGB in adolescents, comparable to those obtained in young adults at 2-year follow-up., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Accumulating evidence suggests that the benefits seen in adult bariatric surgery can be reproduced in adolescents. In contrast with North America, bariatric surgery in adolescents is still not well accepted in Europe and indications and protocols have still to be formulated., Methods: This prospective study tested the gastric banding procedure in 49 patients operated in a single French institution since 2008. The mean age at surgery was 16.2 ± 0.9 years with a weight of 118.8 ± 22.3 kg and body mass index of 42.5 ± 5.9 kg/m(2)., Results: At 6, 12 and 24 months after surgery, weight was 103.7 ± 20.8 kg, 98.7 ± 21 kg and 93.6 ± 19.3 kg, respectively (p < 0.001), corresponding to excess weight loss (EWL) of 31.6 ± 17.2 %, 41.8 ± 21.4 % and 59.1 ± 24.9 % (p < 0.001), respectively. Multivariate analysis showed that the number of consultations per year was the only variable significantly associated to weight loss. Metabolic disorders were corrected, with a decreased prevalence of insulin resistance from 100 to 17 % and normalisation of homeostasis model assessment-insulin resistance (HOMA-IR) at 24 months (2.09 ± 0.95). Band-related complications were five slippages, one psychological intolerance and two ports repositioning. Six patients (12 %) had the device explanted. The death of a patient was an exceptionally severe adverse event., Conclusion: Given frequent follow-up support by a multidisciplinary team, laparoscopic adjustable gastric banding (LAGB) surgery in adolescent results in sustained weight loss. However, even exceptional, potentially serious complications are possible and long-term follow-up is needed to evaluate the risk/benefit ratio at 5 or 10 years after LAGB surgery.

Background: Small bowel transplantation has now become a recognized treatment of irreversible, permanent, and subtotal intestinal failure., Objective: The aim of this study was to assess intestinal absorption at the time of weaning from parenteral nutrition in a series of children after intestinal transplantation., Design: Twenty-four children (age range: 14-115 mo) received intestinal transplantation, together with the liver in 6 children and the colon in 16 children. Parenteral nutrition was slowly tapered while increasing enteral tube feeding. The absorption rate was measured from a 3-d stool balance analysis performed a few days after the child had weaned from parenteral nutrition to exclusive enteral tube feeding. Results were analyzed according to the resting energy expenditure (REE; Schofield formula)., Results: All children were weaned from parenteral nutrition between 31 and 85 d posttransplantation. Median intakes were as follows: energy, 107 kcal · kg(-1) · d(-1) (range: 79-168 kcal · kg(-1) · d(-1)); lipids, 39 kcal · kg(-1) · d(-1) (range: 20-70 kcal · kg(-1) · d(-1)); and nitrogen, 17 kcal · kg(-1) · d(-1) (range: 11-27 kcal · kg(-1) · d(-1)). Median daily stool output was 998 mL/d (range: 220-2025 mL/d). Median absorption rates were 88% (range: 75-96%) for energy, 82% (range: 55-98%) for lipids, and 77% (range: 61-88%) for nitrogen. The ratios for ingested energy to REE and absorbed energy to REE were 2.2 (range: 1.6-3.6) and 1.8 (range: 1.3-3.3), respectively., Conclusion: These data indicate a suboptimal intestinal graft absorption capacity with fat malabsorption, which necessitates energy intakes of at least twice the REE.

Purpose: To evaluate outcome of further continence procedures after failure of endoscopic injections of dextranomer-based bulking agent., Materials and Methods: From 1997, 89 children (3-18 years) and one young adult were treated for incontinence with 145 endoscopic injections of dextranomer. On evaluation, each patient was classified as: dry, significantly improved, or treatment failure. Eighty-five patients had at least 12 months of follow up. Out of 34 (40%) treatment failures, 24 patients had a subsequent bladder neck procedure: artificial urinary sphincter (7), bladder neck plasty (9), bladder neck closure (1), fascial sling (3). Six patients had further endoscopic treatment (including 2 after bladder neck plasty)., Results: At surgery, Deflux(®) paste was easily identified with minimal surrounding tissue inflammatory reaction. Artificial urinary sphincter: all 7 dry; bladder neck plasty: 7 dry, 1 improved and 1 still incontinent; 1 bladder neck closure patient dry; fascial sling: 1 significantly improved and 2 dry. Repeated endoscopic treatment: 1 dry, 1 improved and 4 failed. Eleven of the 21 (52%) patients who are either dry or improved have voiding abilities., Conclusion: Endoscopic injections with dextranomer do not adversely affect the outcome of further surgical procedures. Repeated injections after a previous endoscopic treatment failure have a low success rate., (Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Preoperative samples in the context of complicated appendicitis (CA) are rarely collected, and there is no consensus regarding the optimal antibiotic therapy in children. To help optimize empirical preoperative treatment, we studied clinical and bacteriologic data from a prospective cohort of 93 children with CA in a French hospital. All the bacteria isolated from peritoneal fluids were identified, using phenotypic and/or molecular techniques. The most commonly recovered species were Escherichia coli (71%), Streptococcus group milleri (34%), anaerobes (20%), and Pseudomonas aeruginosa (19%). The association piperacillin-tazobactam is an accurate choice of empirical therapy as it is active against 97% of bacteria. A third-generation cephalosporin with metronidazole in association with an aminoglycoside is a good alternative. Although antibiotic use may be considered as an adjunct to surgical intervention of CA, the appropriate use of preoperative antibiotics is essential and must be constantly reevaluated according to the bacterial epidemiology., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This lecture updates the pediatric surgeon on current indications, techniques, and results of intestinal transplantation in children with intestinal failure with reference to the Paris series., (Copyright © 2011. Published by Elsevier Inc.)

Currarino syndrome (CS) is a rare congenital malformation described in 1981 as the association of three main features: typical sacral malformation (sickle-shaped sacrum or total sacral agenesis below S2), hindgut anomaly, and presacral tumor. In addition to the triad, tethered cord and/or lipoma of the conus are also frequent and must be sought, as they may lead to severe complications if not treated. The HLXB9 gene, located at 7q36, is disease-causing. It encodes the HB9 transcription factor and interacts with DNA through a highly evolutionarily conserved homeodomain early in embryological development. Thus far, 43 different heterozygous mutations have been reported in patients fulfilling CS criteria. Mutation detection rate is about 50%, and reaches 90% in familial cases. Here, we report 23 novel mutations in 26 patients among a series of 50 index cases with CS, and review mutational reports published since the identification of the causative gene. Three cytogenetic anomalies encompassing the HLXB9 gene are described for the first time. Truncating mutations (frameshifts or nonsense mutations) represent 57% of those identified, suggesting that haploinsufficiency is the basis of CS. No obvious genotype-phenotype correlation can be drawn thus far. Genetic heterogeneity is suspected, since at least 19 of the 24 patients without HLXB9 gene mutation harbor subtle phenotypic variations.

Objective: Small bowel (SB) transplantation (Tx), long considered a rescue therapy for patients with intestinal failure, is now a well recognised alternative treatment strategy to parental nutrition (PN). In this retrospective study, we analysed graft functions in 31 children after SBTx with a follow-up of 2-18 years (median 7 years)., Patients: Twelve children had isolated SBTx, 19 had combined liver-SBTx and 17 received an additional colon graft. Growth, nutritional markers, stool balance studies, endoscopy and graft histology were recorded every 2-3 years post-Tx., Results: All children were weaned from PN after Tx and 26 children remained PN-free. Enteral nutrition was required for 14/31 (45%) patients at 2 years post-Tx. All children had high dietary energy intakes. The degree of steatorrhoea was fairly constant, with fat and energy absorption rates of 84-89%. Growth parameters revealed at transplantation a mean height Z-score of -1.17. After Tx, two-thirds of children had normal growth, whereas in one-third, Z-scores remained lower than -2, concomitant to a delayed puberty. Adult height was normal in 5/6. Endoscopy and histology analyses were normal in asymptomatic patients. Chronic rejection occurred only in non-compliant patients. Five intestinal grafts were removed 2.5-8 years post-Tx for acute or chronic rejection., Conclusions: This series indicates that long-term intestinal autonomy for up to 18 years is possible in the majority of patients after SBTx. Subnormal energy absorption and moderate steatorrhoea were often compensated for by hyperphagia, allowing normal growth and attainment of adult height. Long-term compliance is an important pre-requisite for long-term graft function.

Background: More information is needed regarding the prognosis of children receiving home parenteral nutrition (HPN). This article describes 20-year outcome data in children receiving HPN and provides separate profiles for the major pediatric diagnostic subgroups., Patients and Methods: This retrospective study included children who started receiving HPN between January 1, 1980, and December 31, 1999, in a single pediatric HPN center., Results: A total of 302 children were recruited, 230 (76%) with primary digestive disorders and 72 (24%) with nonprimary digestive disorders. Median age at HPN onset was 1.5 years. Median duration of HPN was 1.3 years. By January 1, 2000, 54% had weaned from HPN, 26% were still receiving HPN, 16% had died, and 4% had undergone intestinal transplantation. The survival probabilities at 2, 5, 10, and 15 years were 97%, 89%, 81%, and 72%, respectively. The likelihood and cause of death depended on the underlying diagnosis. Nine percent of children with primary digestive disorders died, 24% from their primary disease and 48% from liver disease or sepsis. Children with intractable diarrhea of infancy had the highest mortality rate (25%) and the highest incidence of liver disease (48%; P = 0.0002). Thirty-eight percent of children with primary nondigestive diseases died, 94% from their primary disease and 6% from liver disease or sepsis., Conclusions: Outcome and survival of children receiving HPN are mainly determined by their underlying diagnosis. Nearly all children with primary digestive disease survive if referred early to an expert center.

Purpose: To treat sphincteric deficiency in children endoscopic bladder neck injections may avoid or salvage more complex procedures. A prospective study to assess the efficacy of bladder neck injections of dextranomer based implants (Deflux(R)) was done in a 7-year period in 61 patients., Materials and Methods: From September 1997 to September 2004 we enrolled in the study 41 males and 20 females 5 to 18 years old with severe sphincteric incompetence, including exstrophy-epispadias in 26, neuropathic bladder in 27, bilateral ectopic ureters in 5, and miscellaneous in 3. Preoperative evaluation consisted of medical history, urine culture, urinary tract ultrasound and videourodynamics. This evaluation was repeated 6 months and 1 year after treatment, and yearly thereafter. Of the patients 17 underwent 2 and 4 underwent 3 treatment sessions to achieve a definitive result. At each evaluation the case was considered cured-a dryness interval of 4 hours between voids or CIC, significantly improved-minimal incontinence requiring no more than 1 pad daily and no further treatment required, and treatment failure-no significant, long lasting improvement. Videourodynamics were mainly useful to study the evolution of bladder capacity, activity and compliance. Followup after the last injection was 6 to 84 months (mean 28)., Results: Mean injected volume per session was 3.9 cc (range 1.6 to 12). Postoperative complications were temporary dysuria in 2 patients nonfebrile urinary tract infection in 10, orchid-epididymitis in 1 and urinary retention with pyelonephritis in 1. The incidence of dryness or improvement during followup was 79% (48 of 61 patients) at 1 month, 56% (31 of 55) at 6 months, 52% (24 of 46) at 1 year, 51% (18 of 35) at 2 years, 52% (16 of 31) at 3 years, 48% (12 of 25) at 4 years, 43% (9 of 21) at 5 years, 36% (4 of 11) at 6 years and 40% (2 of 5) at 7 years. The success rate according to pathological condition was similar in cases of neuropathic bladder and the exstrophy-epispadias complex (48% and 53%, respectively). The success rate in re-treated cases was 38%. After treatment a contracted bladder developed in 6 patients. Also, of the 35 patients with at least 2 years of followup an increase in capacity of at least 50% was observed in 12 of 18 with an initially small bladder. No side effects related to the substance were observed., Conclusions: Endoscopic treatment for pediatric severe sphincteric deficiency with dextranomer implant, a nontoxic, nonimmunogenic, nonmigratory synthetic substance, was effective up to 2 years in half of the patients. Subsequently at up to 7 years of followup a slow decrease in efficacy was observed and treatment remained beneficial in 40% of the patients.

Extramedullary hematopoiesis affects about 15% of the patients treated for thalassemia intermedia. Usually seen in adulthood, the most common location is the paraspinal region. Diagnosis and treatment of extramedullary hematopoiesis located in the pelvis of a young 15-year-old girl is discussed. The young age of the patient and the uncommon site of the mass first lead to the diagnosis of an ovarian dermoid cyst. Because of the clinical history and the typical feature on computed tomography scan, extramedullary hematopoiesis was concluded. A specific treatment based on blood transfusion and hydroxyurea was first proposed but remained inefficient. Surgical excision was thus successfully performed. Whereas surgery is limited to spinal cord compression in paraspinal extramedullary hematopoiesis, this observation argues for surgical treatment in symptomatic intraabdominal extramedullary hematopoiesis when medical treatment fails.

Purpose: The aim of the study was to clearly define the anomalies that compose the Currarino syndrome (CS). We highlight the frequency of associated malformations of the spinal cord and the possibility of a communication between the presacral tumor and the spinal canal, leading to neurological complications., Methods: We studied 29 patients with CS, including 12 familial cases; histological examination of the presacral tumor was performed, and cytogenetic and molecular biology studies of the HLXB9 locus were carried out., Results: All except 2 patients had a sacral malformation; 23 had an anorectal anomaly and 8 had isolated chronic intestinal pseudo-obstruction. There were 20 presacral tumors, one of which was malignant. There was a communication between the presacral tumor and the spinal canal in 12 cases, and tethering of the spinal cord in 17 cases. Twenty-five patients underwent surgery with a single-stage operation for 7, on both the intestinal and the presacral malformations, and, when required, the spinal cord anomalies. Twelve patients harbored a heterozygous point mutation of the coding sequence of HLXB9 gene., Conclusion: By accurate evaluation of the 4 main features in the CS, the correct surgical management, including neurosurgery, can be performed in a 1-stage approach.

Background/purpose: Inflammatory myofibroblastic tumor (IMT) is considered as an intermediate neoplasm that may present malignant features. Differential diagnosis with other tumor processes is sometimes difficult. Similar anaplastic lymphoma kinase (ALK) gene abnormalities as in anaplastic large cell lymphoma have been reported. Human herpesvirus 8 (HHV-8) DNA sequences have been described in adult pulmonary IMTs and Epstein-Barr virus (EBV) has been reported in splenic and hepatic IMTs, suggesting the importance of both viruses in IMT development. This article aims to evaluate ALK, EBV, and HHV-8 expression in children with IMT and to correlate our findings with clinical features., Methods: Sixteen children (range, 1-15 years) who had surgery for IMT between 1978 and 2003 were evaluated retrospectively. Formalin-fixed, paraffin-embedded archival tissues were stained for HHV-8 and ALK with immunohistochemistry. Epstein-Barr virus was detected by in situ hybridization (EBER probes)., Results: Tumors were located in the pulmonary lobe (n = 4), urinary tract (n = 4), mesentery or bowel (n = 4), hepatic lobe (n = 1), vena cava (n = 1), spinal cord (n = 1), and soft tissue (n = 1). Five children were treated with steroids and/or antibiotics before surgery, with no substantial result. IMT was excised totally in all but 2 cases. Four patients presented aggressive IMT with recurrence or metastasis requiring new surgery. ALK was positive in 3 (18.8%) cases and EBV in 1 pulmonary and 1 bladder tumor, all of them without recurrence or metastasis. None of the cases were positive for HHV-8. All patients are now disease-free with a mean follow-up of 4.2 years., Conclusions: Considering the present lack of efficient medical treatment, surgery should still be considered as the mainstay therapy in IMT, even in cases of recurrence or metastases. Larger multicentric studies would be necessary to understand the prognostic significance of ALK, EBV, and HHV-8 and their relationships with the origins of the tumor.

Background: Although intestinal transplantation provides a unique situation of free access to the graft because of the presence of temporary enterostomas, evaluation of local immunosuppression is still an unresolved issue and may constitute one of the causes of grafting failure., Aims: To study in a rat model of allogeneic intestinal transplantation the expression of transcription factors involved in lymphocyte activation in situ in the graft and to identify factors reflecting the efficiency of drug immunosuppression., Methods: Intestinal transplantation was performed in a Brown Norway (RT1n-donors)-Lewis (RT1(l)-recipients) rat strain combination. The animals were treated with tacrolimus to induce tolerance or left untreated. Syngeneic intestinal grafts and intestine from donor rats with peritonitis were used as controls. NF-kappaBp65, p-c-Jun, interleukin 2 receptor (CD25), and major histocompatibility complex class II antigen (OX-6) expression was studied in graft biopsies on days 2 and 5 by immunohistochemistry., Results: On day 2, before the onset of histologic signs of rejection, the number of cells expressing NF-kappaBp65 in the pericryptic lamina propria was significantly higher in untreated recipients of allogeneic grafts than in the other groups (P = .009). NF-kappaBp65 expression then fell between days 2 and 5 (P = .009). Classic markers of T-cell activation (CD25 and OX-6) were expressed during rejection in the lamina propria and on crypt enterocytes, respectively. p-c-Jun expression did not differ among the 3 groups., Conclusion: NF-kappaBp65 expression in intestinal grafts is a precocious sign of local activation during rejection and could thus serve to optimize the management of immunosuppressive therapy.

Advances in immunosuppressive treatment as well as better monitoring and control of acute rejection have brought intestinal transplantation (ITx) into the realm of standard treatment for permanent intestinal failure. The results from the intestinal Transplant International Registry (www.intestinaltransplant.org) indicate that ITx is currently an acceptable clinical modality for selected patients with permanent intestinal failure. The goal of this short review is to deal with indications, clinical results and complications of ITx. Although it has been used in humans for the past two decades, very few data are available regarding graft function and its monitoring.

Background: The authors analyzed clinical signs of vascular ring anomalies together with appropriate complementary examinations and factors predictive of outcome after surgical treatment., Methods: The authors reviewed the files of 62 patients with vascular ring abnormalities treated at Necker-Enfants Malades Hospital between January 1990 and January 2000, to analyze age at symptom onset, results of paraclinical examinations, the type of vascular ring abnormality, the surgical indications and type of surgery, and postoperative outcome. Outcomes were divided into 3 categories: cure, partial improvement, and no improvement. The chi2 test corrected with Fischer's Exact test was used for statistical analysis., Results: Vascular ring abnormalities were diagnosed at birth in 28% of cases and during the first year of life in 68%. Sixteen percent of patients had associated abnormalities. Recurrent pulmonary and bronchial infections occurred after one year of age. An esophagogram was done in 76% of cases and showed impression images. Endoscopy was done in 63% of cases and showed malacia in 41% of patients and stenosis in 51%. Fifty-eight children were treated surgically. The average hospital stay was 7.4 days. The average follow-up was 37.4 months (12 to 159 months). Complete improvement was obtained in 68% of cases, partial improvement in 17%, and no improvement in 15%. Preoperative malacia was more frequent in patients with partial improvement or no improvement., Conclusions: Surgical treatment of congenital vascular ring abnormalities is effective and safe. Complications are rare. Prognostic factors include the quality of preoperative preparation of respiratory function, the type of abnormality, and the degree of malacia., (Copyright 2003, Elsevier Science (USA). All rights reserved.)

The use of small caliber arteries is probably responsible for the higher hepatic artery thrombosis rate initially reported after living related liver transplantation. We described a two-step strategy generating flow-induced enlargement of a small diameter artery in case of left graft dual arterial supply. The smaller arterial branch was ligated during a laparoscopic first-step procedure inducing a 30% enlargement of the remaining branch. The second-step donor hepatectomy was performed 1 week later using a larger artery for successful vascular anastomosis. The flow-induced enlargement of donor hepatic artery may help to reduce hepatic artery thrombosis risk after pediatric living related liver transplantation.

Purpose: Ureterovesical reimplantation is most often performed for renal transplantation in children. We reviewed our experience to evaluate the safety and efficacy of ureteroureteral reimplantation in pediatric renal transplantation., Materials and Methods: We retrospectively evaluated the charts of 92 boys and 72 girls who underwent a total of 166 ureteroureteral anastomoses for renal transplantation from January 1990 to December 1999. Spatulated end-to-end anastomosis was performed between recipient and graft ureters without stenting and with a bladder catheter for at least 10 days., Results: Mean patient age at transplantation was 11.2 years (range 1 to 21.5). There were 22 living related donor and 144 cadaveric grafts. Urological anomalies and nephropathy were the cause of end stage renal disease in 146 and 20 patients, respectively. Urological complications were noted in 14 of the 166 transplantations (8.4%) in 10 boys and 4 girls, including 12 initial and 2 repeat grafts from 2 living related and 12 cadaveric donors. Five of these patients had undergone previous urological surgery. The 2 children (1.2%) with acute ureteral obstruction underwent repeat intervention after stent failure. Anastomotic leakage in 7 cases (4.2%) was treated conservatively in 1 and with a Double-J stent (Medical Engineering Corp., New York, New York) only required in 3. Reoperation was required in 3 cases. One patient (0.6%) with late ureteral stenosis underwent repeat anastomosis, 1 (0.6%) required reimplantation for recurrent pyelonephritis due to vesicoureteral reflux in the graft, 1 (0.6%) with a valve bladder required bladder augmentation and ureteral reimplantation, and 1 (0.6%) with lymphocele and 1 (0.6%) with lithiasis were successfully treated conservatively. Complications were associated with acute rejection in 6 cases. Mean followup without graft loss in patients who presented with versus without complications was 58.3 months (range 1 to 112) versus 75 (range 1 to 118). In the former patients with a mean age of 16 years 9 months versus those without urological complications mean serum creatinine was 116 and 108 mol./l., respectively. Two grafts were lost in patients with urological complications, including 1 who died of pulmonary embolism and 1 with refractory chronic rejection. Seven patients were lost to followup after 54 months (range 12 to 113) of adequate graft function., Conclusions: Ureteroureteral anastomosis is a safe and effective technique for pediatric renal transplantation with a low complication rate, which may be due to better vascularization of the shorter ureteral end of the graft. Our results should encourage the use of this technique in pediatric renal transplantation. Efforts to preserve the recipient ureters should be made at nephrectomy.

Intestinal occlusion occurs in approximately 1 in 3000 births. Its diagnosis can be made in utero with ultrasound however, determination of its precise location is difficult to achieve. We report herein the feasibility of diagnosing and locating a fetal small-intestine occlusion with the use of magnetic resonance imaging.

Background: Small bowel transplantation remains a difficult therapeutic option endangered by a high rate of rejection and infectious complications. To improve these clinical results, it is mandatory to set up animal models to test alternative immunosuppressive regimens which may lead to immunotolerance., Aims: To determine the value of blockade of alphaLbeta2 (LFA-1) and alpha4 and beta7 integrins (alpha4beta1, alpha4beta7, and alphaEbeta7) in the prevention of rejection of fetal small bowel grafts in mice and the effect of the association of calcineurin dependent drugs in anti-LFA-1 treated mice., Methods: Adult recipient mice engrafted with allogeneic fetal small bowel received a short course of anti-alpha4 and/or anti-LFA-1 monoclonal antibodies (mAb) with or without FK506 or cyclosporin A. In addition, in a set of experiment, beta7-/- mice were used as recipients. Graft biopsies were performed and processed for standard histology., Results: Blockade of the pathways of the integrins alpha4 and beta7 had a modest or no effect on intestinal graft survival. In contrast, transitory, short administration of anti-LFA-1 monoclonal antibody alone, when started before engraftment (day -1), allowed long term survival of intestinal grafts, even when associated with calcineurin dependent drugs. However, early withdrawal of FK506 reversed the immunosuppressive effect of anti-LFA-1 treatment., Conclusion: These results suggest that firstly, anti-LFA-1, but not anti-alpha4 mAb treatment, may be useful in improving the results of intestinal transplantation, and secondly, that this treatment is not incompatible with long term administration of tacrolimus currently used in the prevention of small bowel graft rejection in humans.

From November 1994 to November 1998, 20 children (2.5 to 14 years) received a jejunoileal graft alone (SBTx; n = 10) or in combination with the liver (SBLTx; n = 10 and/or the right colon (5 SBTx). Indications were intractable diarrhea of infancy (n = 8), short bowel syndrome (n = 6), extensive Hirschsprung disease (n = 4), and chronic intestinal pseudoobstruction (n = 2). Immunosuppression included tacrolimus, methylprednisolone, and azathioprine. Current follow-up ranges from 6 to 54 months. Five patients died (3 SBTx) within the first 2 months. Acute liver rejection occurred in 5 patients during the first 2 months. Sixteen episodes of intestinal rejection during the first 3 months in 11 patients (8 in 4 SBTx) were successfully treated in all but 3 by increasing tacrolimus dose and/or a 3-day methyprednisolone bolus or required antilymphoglobulins in 3 cases. Surgical complications occurred 8 times after SBLTx and 3 after SBTx. Infectious complications were more frequent in SBLTx recipients. Reversible Epstein-Barr virus-related posttransplant lymphoproliferative disease occurred in 3 recipients. Five presented cytomegalovirus infection. The SB graft was removed in 5 recipients (3 chronic rejection). All patients were started with oral and/or enteral feeding from the 7th postoperative day by using either normal food or protein hydrolysate diet. Currently, 10 of 11 children (8 SBLTx) achieved digestive autonomy after 5 to 30 weeks. All recipients gained weight; however, growth velocity remained reduced during the first 6 months because of the steroid therapy. Overall graft and patient survival is higher after SBLTx. Intestinal transplantation is indicated for patients with permanent intestinal failure. However, because parenteral nutrition is generally well tolerated, even for long periods, each indication for transplantation must be weighed carefully in terms of risk and quality of life.

Purpose: The aim of the authors was to report their experience with living related liver transplantation (LRLT) in children, particularly focusing on the safety of the two-center "Parisian" strategy., Methods: The records of donors and recipients of 26 pediatric living-related donor liver transplantations performed between November 1994 and March 1998 were reviewed retrospectively. Donors were assessed 1 year after transplantation for medical and overall status., Results: Indications for LRLT included biliary atresia (n = 18), Byler's disease (n = 5), alpha-1-antitrypsin deficiency (n = 1), Alagille syndrome (n = 1), and undefined cirrhosis (n = 1). Liver harvesting consisted of either a complete left hepatectomy (n = 14) or left lateral hepatectomy (n = 12) without vascular clamping. The recipient procedure essentially was the same as in split liver transplantation. Mean overall cold ischemia time averaged 140 minutes (range, 90 to 230 minutes). Twenty-four of 26 patients had end-to-end vascular anastomoses without interposition. Biliary reconstruction consisted of a Roux-en-Y choledochojejunostomy in all patients. All recipients except one received cyclosporine A (CSA). Mean donor hospitalization was 8 days (range, 6 to 13) with normalization of all liver function assays by the time of discharge. There were no donor deaths and two postoperative complications (perihepatic fluid collection and bleeding from the wound). One year after donation, the initial 19 donors had resumed their pretransplant status. Two of the children who underwent transplant died. Thirteen of the recipients required reoperation for hepatic artery thrombosis (n = 2), portal vein thrombosis (n = 2), biliary complications (n = 6), fluid collection (n = 3), small bowel perforation (n = 1), and plication for diaphragmatic eventration (n = 1). With mean follow-up of 2 years, 24 of 26 patients are alive and well (patient and graft survival rate, 92%)., Conclusions: LRLT is still controversial, even with minimal and decreasing donor risk. The "Parisian" strategy consists of harvesting the liver in an adult unit by an adult hepatic surgery team. The transplantation is then performed in a pediatric hospital by the pediatric liver transplantation team. The two steps of the procedure allow units specialized in adult surgery, on one hand, and pediatric liver transplantation, on the other hand, to dedicate themselves completely to their respective procedures, improving the safety of the harvest, and alleviating stress for both the medical staff and the families.

Purpose: The aim of the authors was to report an up-to-date review of their experience with 26 intestinal transplantations in children since 1987., Methods: A retrospective study was conducted of 26 patients with a mean age of 5 years (range, 0.3 to 14 years). Three groups were isolated. In group A (1987 to 1990), seven patients received nine isolated intestinal transplants for short bowel syndrome. Immunosuppression therapy consisted of cyclosporine, aziathioprine, and corticosteroids. In group B (1994-current), nine patients received nine isolated intestinal transplants for short bowel syndrom (n = 2), intestinal pseudoobstruction (n = 2), neonatal intractable diarrhea (n = 3), and Hirschsprung' disease (n = 1); hepatic biopsy results showed weak cholestasis or fibrosis. In group C (1994-current), 10 patients received 10 combined liver-small bowel transplants for short bowel syndrome (n = 3), neonatal intractable diarrhea (n = 4), and Hirschsprung' disease (n = 3); hepatic cirrhosis related to total parenteral nutrition (TPN) was shown in all cases. Groups B and C received immunosupressive treatment consisting of tacrolimus, aziathioprine, and corticosteroids. Posttransplant follow-up included intestinal biopsies of the small bowel twice a week and more frequently or combined with liver biopsy if rejection was suspected., Results: Overall patient survival (PS) and graft survival (GS) are 61% (16 of 26) and 50% (13 of 26), respectively. In group A, severe intestinal allograft rejection occurred in six patients leading to graft removal (GS, 11%). Five patients died of TPN complications after graft removal (PS, 28%). One survivor is off TPN, and one currently is waiting for a second graft. In group B, six patients survived (PS, 66%). Causes of death include hepatic failure (n = 1), renal and liver failure (n = 1), and systemic infection (n = 1). Severe intestinal allograft rejection occurred in five patients, which neccessitated aggressive immunosuppression (antilymphocyte serum) leading to an incomplete functional recovery of the graft. Only two patients currently are off TPN. In group C, eight patients survived (PS, 80%) all of which are currently off TPN. One patient died during the procedure, and one died of severe systemic infection. Intestinal graft rejection occurred in six patients; rejection of the liver allograft occurred in five patients, yet all rejections were weak and successfully treated by corticosteroids (GS, 80%)., Conclusions: Intestinal transplantation is a valid therapeutic option for children with definitive intestinal failure and not only for short bowel syndrome. Tacrolimus improves graft and patient survival (group A v group B). The lower severity of graft rejection in combined liver-small bowel transplantation improves functional results of intestinal transplantation in children without additional mortality or morbidity (group B vgroup C).

Background: In a previous study, it was shown that a spontaneously tolerated DA (RT1a) liver allograft in a PVG (RT1c) recipient was able to induce tolerance of a DA small bowel graft performed 17 days later in spite of infiltration of the intestinal grafts by mononuclear cells., Aims: To compare the phenotype of graft infiltrating cells in rejecting and tolerated small bowel grafts in order to elucidate the mechanism(s) which block the graft infiltrating cells from mediating rejection., Methods: Multiparameter immunofluorescence was used to compare the phenotype and state of activation of donor and recipient cells isolated from intestinal grafts rejected or tolerated after liver transplantation., Results: Three differences were found. Firstly, there was a more rapid replacement of lamina propria (LP) cells by recipient lymphocytes in tolerated than in rejected grafts. Secondly, the proportion of LP recipient CD8alphabeta+ lymphocytes bearing the high affinity receptor for interleukin 2 was significantly less in tolerated grafts (1.1%, range 0-2%) than in rejected grafts (21.3%, range 9-26%). Finally, tolerated grafts contained significantly less NK lymphocytes (NKR-P1+) and macrophages than rejected intestinal allografts., Conclusions: These observations make it possible to delineate clear cut differences in the phenotype of cells infiltrating rejecting versus tolerated grafts. Furthermore, the data suggest that liver transplantation induces tolerance of intestinal grafts by hampering the activation of recipient TcRalphabeta+ CD8alphabeta+ T cells and subsequently the recruitment of non-specific effector cells.

Objective: Although aggressive fetal therapies such as thoracoamniotic shunting can be applied to cystic adenomatoid malformations of the lung diagnosed in utero, there is no clear consensus regarding their indications. Our purpose was to evaluate a management policy in which aggressive fetal therapy was restricted to those cases complicated by major polyhydramnios or hydrops; all other cases were managed conservatively., Study Design: A prospective cohort study of 33 cases with a prenatal diagnosis of cystic adenomatoid malformations of the lung was performed. Thoracoamniotic shunting was offered only in nine macrocystic cases with acute polyhydramnios or hydrops., Results: Four cases were diagnosed postnatally as sequestrations. Of 12 cases complicated by acute polyhydramnios or hydrops, 5 survived (1 type III with spontaneous incomplete resolution in utero, 4 type I with substantial volume reduction after shunting). The 17 cases without acute polyhydramnios or hydrops were managed conservatively and survived., Conclusion: Conservative management is indicated in cases of cystic adenomatoid malformations of the lung without acute polyhydramnios or hydrops.

Seven children with short bowel syndrome underwent small bowel allografting. Episodes of early rejection were observed in five patients who received a graft from paediatric or adult donors but not in two patients who received a neonatal graft. This study aimed, firstly, to define immunohistochemical parameters accompanying rejection and, secondly, to compare immunohistochemical parameters in neonatal grafts with those in grafts from older donors. An immunohistochemical analysis was performed on 85 intestinal biopsy specimens taken for monitoring the transplant. Acute histological rejection was associated with pericryptic infiltrates of CD3+TcR alpha beta + T cells containing clusters of CD8+ cells, numerous CD25+ cells, and increased numbers of CD68+ macrophages. These changes were associated with the appearance of major histocompatibility (MHC) class II antigens on crypt enterocytes and with an appreciable increase in the expression of E-selectin on mucosal endothelial cells. Immunohistochemistry was useful in predicting rejection by showing the appearance of pericryptic CD25+ T cells 48 hours before the first histological lesions of crypt necrosis. Comparison of neonatal grafts with grafts from older donors did not show any significant difference in the density of CD68+ macrophages or in the endothelial expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or E-selectin. In contrast to grafts from older donors, however, neonatal grafts did not express MHC class II antigens on epithelial cells and contained very low numbers of intraepithelial lymphocytes. These data indicate, firstly, that immunohistochemistry is useful for monitoring intestinal transplants and, secondly, that the better clinical tolerance of neonatal allografts may be related to the lower immunogenicity of the neonatal epithelium.

In utero evolution and postnatal outcome were studied for 18 cases of congenital adenomatoid malformation (CAM) diagnosed by prenatal ultrasound. Five were macrocystic CAM, 9 were microcystic, and 4 were homogeneously hyperechogenic. Three fetuses presented with hydrops. Pulmonary amniotic shunting was performed in 3 patients. Outcome was the following: 4 were aborted, 1 died neonatally, and 13 survived. Four of these infants required no surgery in the neonatal or postneonatal period. In three of these, the size of the mass had decreased spontaneously in utero. Outcome did not appear to be related to the anatomic type of CAM nor to the presence of moderate polyhydramnios, but was related to the degree of mediastinal compression and to the existence of hydrops. A clearer understanding of the natural evolution of CAM is useful to determine the indications for in utero therapy.

Pheochromocytoma is an uncommon tumor in childhood; nevertheless, 20% of all pheochromocytomas are found in the pediatric population. Fifteen children have been treated in our institution from 1962 to 1990. One percent of patients referred over the same period for investigation of high blood pressure were found to have a pheochromocytoma. The majority of patients have hypertension. It varies in intensity and is paroxysmal in about half the patients. Many pediatric cases of unilateral, bilateral, extra-adrenal, familial, and recurrent pheochromocytomas have been reported. We reviewed our 28 years experience with this tumor and concentrated on the diagnosis, the preoperative and operative management, and the occurrence of the multiple endocrine neoplasia syndromes.

A group of 176 patients aged 2 to 15 years was investigated for idiopathic disorders of bowel function other than Hirschsprung's disease. Anorectal motility, as well as colorectal transit of radiopaque markers, were investigated. Before the end of the first month of life, 70 of the patients were constipated. Resting pressure was more unstable (P less than 0.001) and higher than normal in the rectal ampulla and upper anal canal (P less than 0.01). Retardation of markers occurred in the proximal and/or distal large bowel of 61% of the patients. The existence of functional abnormalities was demonstrated in the majority of children with idiopathic disorders of fecal continence.