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

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

Congenital bile duct cyst (BDC) is a more indolent disease in children compared to adults, except for Todani type IV-A BDC: results of the European multicenter study of the French Surgical Association.

AIM: To compare clinical presentation, operative management and short- and long-term outcomes of congenital bile duct cysts (BDC) in adults with children. METHODS: Retrospective multi-institutional Association Francaise de Chirurgie study of Todani types I+IVB and IVA BDC. RESULTS: During the 37-year period to 2011, 33 centers included 314 patients (98 children; 216 adults). The adult population included more high-risk patients, with more active, more frequent prior treatment (47.7% vs 11.2%; p < 0.0001), more complicated presentation (50.5% vs 35.7%; p = 0.015), more synchronous biliary cancer (11.6% vs 0%; p = 0.0118) and more major surgery (23.6% vs 2%; p < 0.0001), but this latter feature was only true for type I+IVB BDC. Compared to children, the postoperative morbidity (48.1% vs 20.4%; p < 0.0001), the need for repeat procedures and the status at follow-up were worse in adults (27% vs 8.8%; p = 0.0009). However, severe postoperative morbidity and fair or poor status at follow-up were not statistically different for type IVA BDC, irrespective of patients' age. Synchronous cancer, prior HBP surgery and Todani type IVA BDC were independent predictive factors of poor or fair long-term outcome. CONCLUSION: BDC is a more indolent disease in children compared to adults, except for Todani type IV-A BDC.

Loss-of-function of MYO5B is the main cause of microvillus inclusion disease: 15 novel mutations and a CaCo-2 RNAi cell model.

Autosomal recessive microvillus inclusion disease (MVID) is characterized by an intractable diarrhea starting within the first few weeks of life. The hallmarks of MVID are a lack of microvilli on the surface of villous enterocytes, occurrence of intracellular vacuoles lined by microvilli (microvillus inclusions), and the cytoplasmic accumulation of periodic acid-Schiff (PAS)-positive vesicles in enterocytes. Recently, we identified mutations in MYO5B, encoding the unconventional type Vb myosin motor protein, in a first cohort of nine MVID patients. In this study, we identified 15 novel nonsense and missense mutations in MYO5B in 11 unrelated MVID patients. Fluorescence microscopy, Western blotting, and electron microscopy were applied to analyze the effects of MYO5B siRNA knock-down in polarized, brush border possessing CaCo-2 cells. Loss of surface microvilli, increased formation of microvillus inclusions, and subapical enrichment of PAS-positive endomembrane compartments were induced in polarized, filter-grown CaCo-2 cells, following MYO5B knock-down. Our data indicate that MYO5B mutations are a major cause of microvillus inclusion disease and that MYO5B knock-down recapitulates most of the cellular phenotype in vitro, thus independently showing loss of MYO5B function as the cause of microvillus inclusion disease.

Lung resection in cystic fibrosis: a survival analysis.

Lung resection may be considered for cystic fibrosis (CF) patients showing localized severe chronic atelectasis and/or bronchiectasis. Nonetheless, literature on survival after surgery is scarce. This study was carried out to assess survival time after partial lung resection. Twenty-one CF patients were operated from 1988 to 2003 and were followed until November 30th, 2004. Survival analysis was performed through Kaplan-Meier method. Mean age at resection was 8.09 years (SD 4.40 years) and two-thirds were females. Z-scores for height, weight, and body mass index as well as FEV1 values showed no statistical significance when comparing values obtained from 2 years before to 2 years after resection. Eleven years after resection, survival probability was 93.8%. Our results suggest that lobectomy or segmentectomy are safe procedures and should be considered in carefully selected patients with unilateral severe symptomatic localized and chronic persistent atelectasis and/or bronchiectasis refractory to conservative management.

Bronchopulmonary sequestrations in a paediatric centre: ongoing practices and debated management.

OBJECTIVES: Bronchopulmonary sequestration (BPS) is the second most common congenital lung malformation, with an estimated incidence ranging from 0.15% to 1.8%. Surgical treatment is elective in patients with symptoms, but the management of asymptomatic patients remains controversial. METHODS: We retrospectively reviewed the medical records of 99 patients treated for BPS in our institution from January 2000 to December 2015. BPS was diagnosed prenatally in 86 (87%) cases. Management throughout this 16-year period was based on 3 interventions: resection by open surgery, resection by thoracoscopy and embolization. RESULTS: Among the 86 patients with a prenatal diagnosis of BPS, 14% had symptoms at birth and 10% had delayed symptoms at a median delay of 8 months (4.5-42 months). For the other 13 patients, symptoms occurred at a median age of 34 months (range 3-96 months). Embolization of the feeding vessel was performed in 46 patients with 6 secondary surgical resections (13%). A total of 59 patients were operated on: 23 cases by open surgery and 36 cases by thoracoscopy. The mean hospitalization stay was significantly longer for open surgery: 4.8 ± 1.3 days vs 4.1 ±1.5 days, respectively (P = 0.03). Differences in hospitalization stay were also found between asymptomatic and symptomatic patients: 3.5 ± 1.2 vs 5.1 ±1.6 days, respectively (P = 0.002). Two of the operated patients died. CONCLUSIONS: When surgery is chosen, thoracoscopy appears to be a valuable procedure. A better understanding of the natural history of BPS is still needed to define the optimal management and the respective roles of surgery, embolization or non-interventional follow-up.

Study of the impact of liver transplantation on the outcome of intestinal grafts in children.

BACKGROUND: Successful small bowel transplantation remains a challenge due to the septic and immune content of the gut. The possible beneficial role of the liver was assessed in pediatric recipients of isolated intestinal and liver intestinal combined transplantation, receiving the same immunosuppressive therapy. METHODS: Fifteen children who underwent small bowel transplantation (seven SbTx) or combined liver-small bowel transplantation (eight LSbTx) at a single center between 1994 and 1998 were retrospectively reviewed and compared with fifteen controls (eight normal and seven appendicitis as inflammatory control). Transplant and patient survival, acute rejection episodes were analyzed and compared. Epithelial apoptotic body counts (ABC) and NF-kB (p65), Caspase-3 and Bax intestinal immunostaining from days 0 to 20 after transplantation were assessed. RESULTS: Graft and patient survivals at 5 years were respectively 75% and 75% in LSbTx; 43% and 57% in SbTx (NS). Histological analysis showed higher ABC in LSbTx intestinal mucosa (P = 0.05 on day 5, P < 0.01 thereafter). Immunostaining of biopsies on day 0 after reperfusion showed different expression of NF-kB, Caspase-3 and Bax on endothelial (P < 0.05 for NF-kB and Bax), mononuclear (P < 0.05 for Bax) and epithelial cells in LSbTx and SbTx. CONCLUSIONS: Our results suggest a protective role of the liver toward intestinal transplantation even in absence of significative difference, probably due to the small number of children. Early changes in NF-kB immunostaining in the biopsies sampled on day 0, pointed to a possible beneficial effect of the liver in the very early phase following transplantation, perhaps through the differential control of ischemia-reperfusion.

The transmanubrial approach: a new operative approach to cervicothoracic neuroblastoma in children.

BACKGROUND: Cervicothoracic neuroblastoma originates from the cervical sympathetic nerves and ganglia and thus presents a problem when dissecting the vascular and nervous elements of the subclavian region. The standard operation is based on thoracotomy or dual cervicotomy/thoracotomy, but these approaches do not provide optimal control of the subclavian vessels. We report our experience in children with cervicothoracic neuroblastoma by using a technique usually performed for apical lung cancer. METHODS: Four patients with localized cervicothoracic neuroblastoma with no N-myc amplification were resected after chemotherapy by this approach. The anatomic evaluation was performed preoperatively with angio-magnetic resonance imaging. This transmanubrial approach, performed through a manubrial L-shaped transection and first costal cartilage resection, affords excellent access to the subclavian region with safe control of the vessels and nerves and exposure of the first 4 thoracic intervertebral foramina. RESULTS: Removal of more than 90% of the tumor was possible in all cases. The postoperative course was uneventful in 3 cases, and the fourth patient with a left-sided tumor had a transient chylothorax. No recurrence occurred with a follow-up period of 8 to 32 months. CONCLUSIONS: The transmanubrial approach is an osteomuscular-sparing technique that seems particularly suitable for the treatment of these tumors, which require a resection that is as complete as possible to avoid postoperative chemotherapy and tumor relapse.

Comparative results of gastric banding in adolescents and young adults.

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.

Primordial Influence of Post-operative Compliance on Weight Loss After Adolescent Laparoscopic Adjustable Gastric Banding.

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.

Impact of previous cyst-enterostomy on patients' outcome following resection of bile duct cysts.

AIM: To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts (BDC) resection. METHODS: A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association. Only Todani subtypes I and IVb were included. Diagnostic imaging studies and operative and pathology reports underwent central revision. Patients with and without a previous history of cyst-enterostomy (CE) were compared. RESULTS: Among 243 patients with Todani types I and IVb BDC, 16 had undergone previous CE (6.5%). Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis (75% vs 22.9%, P < 0.0001), had more complicated presentations (75% vs 40.5%, P = 0.007), and were more likely to have synchronous biliary cancer (31.3% vs 6.2%, P = 0.004) than patients without a prior CE. Overall morbidity (75% vs 33.5%; P < 0.0008), severe complications (43.8% vs 11.9%; P = 0.0026) and reoperation rates (37.5% vs 8.8%; P = 0.0032) were also significantly greater in patients with previous CE, and their Mayo Risk Score, during a median follow-up of 37.5 mo (range: 4-372 mo) indicated significantly more patients with fair and poor results (46.1% vs 15.6%; P = 0.0136). CONCLUSION: This is the large series to show that previous CE is associated with poorer short- and long-term results after Todani types I and IVb BDC resection.

Centrilobular necrosis in children after combined liver and small bowel transplantation.

BACKGROUND: Centrilobular necrosis is not an uncommon finding after isolated liver transplantation. In this study, we sought to describe hepatic centrilobular necrosis in children after combined liver and small bowel transplantation (LSBT), and to assess the predictive factors, possible causes, and prognosis. METHODS: Six children aged 4 to 11 years, in whom liver biopsy showed centrilobular necrosis at least once, 3 weeks to 2 years after LSBT, were compared with nine children without this pathology. All six children experienced an acute complication in the few weeks preceding the finding of centrilobular necrosis. In addition, one child had an early arterial thrombosis and one, severe colitis 3 years after LSBT. RESULTS: Centrilobular necrosis was associated with centrilobular swelling, dropout, endotheliitis, and inflammation. Fibrosis developed early and worsened on follow-up biopsy in three children. Portal symptoms of acute rejection were not constant, and there was no ductopenia. Biologic abnormalities were responsive to increased immunosuppression, including mycophenolate in four cases. However, follow-up biopsies showed persistent lesions in five patients, mildly inflammatory in four. Baseline immunosuppression had to be maintained at high levels. No viral infections, vascular compromise (except in one), and autoimmunity were found. We compared the two groups of children for initial diagnosis, age at transplantation, time receiving parenteral nutrition, ischemic time, presence of an associated transplanted colon, number of reoperations and infections, intestinal rejection, and immunosuppression, and found no differences. CONCLUSIONS: This severe manifestation of chronic liver rejection occurred despite the heavy immunosuppression needed for LSBT. The previous acute clinical event could have triggered rejection by modifying the effective immunosuppression at the tissue level. Despite high baseline immunosuppression, histologic lesions persisted and significant fibrosis developed in half the children. We speculate that the lack of induction of tolerance in this particular setting of LSBT could be responsible for constant immune stimulation, thus chronic rejection. The optimal protocol of immunosuppression has yet to be defined to avoid this complication.

A two-step strategy for enlargement of left arterial branch in a living related liver graft with dual arterial supply.

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.

New perspectives for children with microvillous inclusion disease: early small bowel transplantation.

BACKGROUND: Microvillous inclusion disease (MVID) is a congenital intestinal epithelial cell disorder leading to lifelong intestinal failure. Despite long-term total parenteral nutrition, life expectancy is extremely reduced because of metabolic or septic complications or liver failure. METHODS: Twelve patients with early-onset MVID were evaluated between 1995 and 2002 for the possibility of small bowel transplantation (SbTx). Three patients died before they could be placed on the waiting list for SbTx, and one patient is still awaiting SbTx. SbTx was contraindicated in one patient. RESULTS: Seven of 12 patients (six boys and one girl) underwent transplantation (three SbTxs and four combined liver-SbTxs). Actuarial survival rates were 100% and 75% in the SbTx and combined liver-SbTx groups, respectively, with a mean follow-up of 3 years (1.1-8.5 years). In contrast, the survival rate was only 40% in the subgroup of five patients who did not undergo transplantation. After transplantation, all patients were weaned from parenteral nutrition: the five patients with an additional colon graft were weaned within 36 days as opposed to the others without colonic transplant who obtained full intestinal autonomy several months after transplantation. The only two surviving patients who did not undergo SbTx remain highly dependent on total parenteral nutrition, which is complicated by repeated episodes of metabolic decompensation. CONCLUSIONS: SbTx alone or in combination with the liver is highly successful in children with MVID, offering them a long-term perspective for the first time. Associated colon grafting markedly improves the outcome and quality of life after SbTx in patients with MVID.

Intestinal transplantation.

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.

[Lynch syndrome pediatric: about a case]. / Le syndrome de Lynch existe en pédiatrie.

A duodenal carcinoma centered on the vater ampulla is reported in a child of 15 years with Lynch syndrome. This case illustrates the problem of early diagnosis and treatment of Lynch syndrome associated tumors.

Extralobar pulmonary sequestration with combined gastric and intradiaphragmatic locations.

Extralobar pulmonary sequestration is a congenital lung malformation characterized by a non-functional lung segment with systemic feeding vessel. Over 90% of sequestrations are found in the thorax with less than 10% located in the abdomen. We present an unusual case of intra abdominal pulmonary sequestration, located suprarenally, adherent to both the stomach and the diaphragm. The malformation was surgically excised via laparoscopy in the second year of life, when no evidence of regression was found on follow up imaging. On the occasion of this description, the spectrum of bronchopulmonary foregut malformation is discussed.

Prenatal intestinal obstruction affects the myenteric plexus and causes functional bowel impairment in fetal rat experimental model of intestinal atresia.

BACKGROUND: Intestinal atresia is a rare congenital disorder with an incidence of 3/10,000 birth. About one-third of patients have severe intestinal dysfunction after surgical repair. We examined whether prenatal gastrointestinal obstruction might effect on the myenteric plexus and account for subsequent functional disorders. METHODOLOGY/PRINCIPAL FINDINGS: We studied a rat model of surgically induced antenatal atresia, comparing intestinal samples from both sides of the obstruction and with healthy rat pups controls. Whole-mount preparations of the myenteric plexus were stained for choline acetyltransferase (ChAT) and nitric oxide synthase (nNOS). Quantitative reverse transcription PCR was used to analyze mRNAs for inflammatory markers. Functional motility and permeability analyses were performed in vitro. Phenotypic studies were also performed in 8 newborns with intestinal atresia. In the experimental model, the proportion of nNOS-immunoreactive neurons was similar in proximal and distal segments (6.7±4.6% vs 5.6±4.2%, p = 0.25), but proximal segments contained a higher proportion of ChAT-immunoreactive neurons (13.2±6.2% vs 7.5±4.3%, p = 0.005). Phenotypic changes were associated with a 100-fold lower concentration-dependent contractile response to carbachol and a 1.6-fold higher EFS-induced contractile response in proximal compared to distal segments. Transcellular (p = 0.002) but not paracellular permeability was increased. Comparison with controls showed that modifications involved not only proximal but also distal segments. Phenotypic studies in human atresia confirmed the changes in ChAT expression. CONCLUSION: Experimental atresia in fetal rat induces differential myenteric plexus phenotypical as well as functional changes (motility and permeability) between the two sides of the obstruction. Delineating these changes might help to identify markers predictive of motility dysfunction and to define guidelines for post-surgical care.

Intestinal absorption rate in children after small intestinal transplantation.

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.

Successful management of congenital bronchial stenosis using an expandable stent.

Congenital bronchial stenosis is a very rare cause of neonatal dyspnea. Surgical management remains challenging in small children. We report successful implantation of a bronchial stent in a 3-month-old female infant presenting with congenital right bronchial stenosis and 18 months of follow-up. Use of stents in children remains controversial because of the problem of size mismatch as the child grows. Nevertheless, expandable stent implantation could be an interesting alternative to complex surgery for localized bronchial stenosis in neonates.