F Lacaille

Université René Descartes - Paris 5, Lutetia Parisorum, Île-de-France, France

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Publications (140)345.13 Total impact

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    ABSTRACT: Intestinal failure-associated liver disease (IFALD) is the most prevalent complication affecting children with intestinal failure receiving long-term parenteral nutrition (PN). We review here the definition, diagnostic criteria, pathogenesis and risk factors. We discuss the role of enteral nutrition, PN and its components, especially lipid emulsions. We discuss the surgical treatment, including intestinal transplantation, its indications, technique and results. We emphasize the importance of specialized intestinal failure centres.
    Journal of pediatric gastroenterology and nutrition. 09/2014;
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    ABSTRACT: Pulmonary alveolar proteinosis (PAP) is very rare in children. Only a few small series have been published, with little information about long-term progression. The objective of our study was to describe the clinical, radiological and pathological features, and the long-term course of PAP in a cohort of 34 children from La Reunion Island.
    Orphanet Journal of Rare Diseases 06/2014; 9(1):85. · 4.32 Impact Factor
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    ABSTRACT: To characterize the effect of donor and recipient CYP3A4, CYP3A5 and ABCB1 genotypes as well as relevant patient characteristics on tacrolimus pharmacokinetics in pediatric liver transplantation.
    Pharmacogenomics 06/2014; 15(9):1207-21. · 3.86 Impact Factor
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    ABSTRACT: Background and aims Chronic intestinal failure (CIF) requires long term parenteral nutrition (PN) and, in some patients, intestinal transplantation (ITx). Indications and timing for ITx remain poorly defined. In the present study we aimed to analyse causes and outcome of children with CIF. Methods 118 consecutive patients referred to our institution were assessed by a multidisciplinary team and four different categories were defined retrospectively based on their clinical course: Group 1: patients with reversible intestinal failure; group 2: patients unsuitable for ITx, group 3: patients listed for ITx; group 4 : patients stable under PN. Analysis involved comparison between groups for nutritional status, central venous catheter (CVC) related complications, liver disease, and outcome after transplantation by using non parametric tests, Mann-Whitney tests, Kruskal-Wallis, Wilcoxon signed rank tests and chi square distribution for percentage. Results 118 children (72 boys) with a median age of 15 months at referral (2 months - 16 years) were assessed. Etiology of IF was short bowel syndrome [n=47], intractable diarrhea of infancy [n=37], total intestinal aganglionosis [n=18], and chronic intestinal pseudoobstruction [n=17]. Most patients (89.8%) were totally PN dependent, with 48 children (40.7%) on home-PN prior to admission. Nutritional status was poor with a median body weight at -1.5 z-score (ranges: -5 to +2,5) and median length at -2,0 z-score (ranges: -5.5 to +2.3). The mean number of CVC inserted per patient was 5.2 (range 1 - 20) and the mean number of CRS per patient was 5.5 (median: 5; range 0 – 12) Fifty-five patients (46.6%) had thrombosis of ≥ 2 main venous axis. At admission 34.7% of patients had elevated bilirubin (≥ 50 μmol/l), and 19.5% had platelets < 100 000/ml, and 15 % had both. Liver biopsy performed in 79 children was normal (n=4), or showed F1 or F2 fibrosis (n= 29), bridging fibrosis F3 (n=20), or cirrhosis (n=26). Group 1 included 10 children finally weaned from PN (7-years survival: 100%). Group 2 included 12 children with severe liver disease and associated disorders unsuitable for transplantation (7-years survival: 16.6%). Group 3 included 66 patients (56%) who were listed for small bowel or liver-small bowel transplantation, 62/66 have been transplanted (7years survival: 74.6%). Factors influencing outcome after liver-ITx were body weight (p<.004), length (p<.001), pre-Tx bilirubin plasma level (p<.001) and thrombosis (p<.01) for isolated ITx, Group 4 included 30 children (25.4%) with irreversible IF considered as potential candidates for isolated ITx. Four children were lost from follow up and 3 died within 2 years (survival 88,5%). Among potential candidates, the following parameters improved significantly during the first 12 months of follow up: Body weight (p.0001), length (p<.0001) and bilirubin (p<.0001). Conclusions many patients had a poor nutritional status with severe complications especially liver disease. PN related complications were the most relevant indication for ITx, but also a negative predictor for outcome. Early patient referral for Tx-assessment might help to identify and separate children with irreversible IF from children with transient IF or uncomplicated long-term PN, allowing to adapt a patient-based treatment strategy including or not ITx.
    Clinical Nutrition. 01/2014;
  • Journal of Crohn's and Colitis. 01/2014; 8:S398.
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    ABSTRACT: Background and aims: Microvillous Inclusion Disease (MVID) is a congenital disorder of the enterocyte related to mutations in the MYO5B gene, leading to intractable diarrhea indicating intestinal transplantation (ITx). Among our cohort of 28 MVID patients, 8 developed a cholestatic liver disease akin to progressive familial intrahepatic cholestasis (PFIC). Our aim was to investigate the mechanisms by which MYO5B mutations affect hepatic biliary function and lead to cholestasis in MVID patients. Methods: Clinical, biological features and outcome were reviewed. Pre-transplant liver biopsies were analyzed by immunostaining and electron microscopy. Results: Cholestasis occurred before (n=5) or after (n=3) ITx and was characterized by intermittent jaundice, intractable pruritus, increased serum bile acid (BA) levels and normal gamma-glutamyl transpeptidase activity. Liver histology showed canalicular cholestasis, mild to moderate fibrosis and ultrastructural abnormalities of bile canaliculi. Portal fibrosis progressed in 5 patients. No mutation in ABCB11/BSEP or ATP8B1/FIC1 genes were identified. Immunohistochemical studies demonstrated abnormal cytoplasmic distribution of MYO5B, RAB11A and BSEP in hepatocytes. Interruption of enterohepatic BA cycling after partial external biliary diversion or graft removal proved the most effective to ensure long-term remission. Conclusion: MVID patients are at risk of developing a PFIC-like liver disease that may hamper outcome after ITx. Our results suggest that cholestasis in MVID patients results from: (i) impairment of the MYO5B/RAB11A apical recycling endosome pathway in hepatocytes (ii) altered targeting of BSEP to the canalicular membrane (iii) and increased ileal BA absorption. Because cholestasis worsens after ITx, indication of a combined liver-ITx should be discussed in MVID patients with severe cholestasis. Future studies will need to address more specifically the impact of MYO5B dysfunction in BA homeostasis. (Hepatology 2013;).
    Hepatology 12/2013; · 12.00 Impact Factor
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    ABSTRACT: Simpson-Golabi-Behmel syndrome type 1 (SGBS1) -OMIM 312870- is a rare X-linked inherited overgrowth syndrome caused by a loss of function mutation in the GPC3 gene. Affected patients present a variable phenotype with pre- and post-natal macrosomia, distinctive facial dysmophism, organomegaly, and multiple congenital anomalies. Intellectual disability is not constant. About 10% of patients have an increased risk of developing embryonic tumors in early childhood. Only one case of biliary disease has been described so far. GPC3 is localized on Xq26. It encodes for glypican 3, a heparan sulfate proteoglycan, which among its different known roles, negatively regulates liver regeneration and hepatocyte proliferation. This report concerns a male with a SGBS1, carrier of a GPC3 pathogenic mutation, and neonatal liver disease, who developed an early biliary cirrhosis. Together with the associated risk of cancer and developmental delay, liver transplantation was discussed and then successfully performed at the age of 19 months. A hypothesis on the role of GPC3 in the patient's liver disease is also proposed. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 12/2013; · 2.30 Impact Factor
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    ABSTRACT: A 3-year-old girl suffering from ornithine carbamoyltransferase (OTC) deficiency was poorly equilibrated under conventional diet and scavenger treatment. Following unsuccessful cryopreserved hepatocyte transplantation, she received two infusions of Adult Derived Human Liver Stem/Progenitor Cells (ADHLSCs) expanded in vitro under GMP settings, the quantity being equivalent to 0.75% of her calculated liver mass. Using FISH immunostaining for the Y chromosome, the initial biopsy did not detect any male nuclei in the recipient liver. Two liver biopsies taken 100 days after ADHLSC transplantation showed 3% and 5% of male donor cells in the recipient liver, thus suggesting repopulation by donor cells. Although limited follow-up did not allow us to draw conclusions on long-term improvement, these results provide a promising proof of concept that this therapy is feasible in an OTC patient.
    JIMD reports. 10/2013;
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    ABSTRACT: Congenital tufting enteropathy (CTE) is a rare and severe enteropathy recently ascribed to mutations in the epcam gene. Here we establish SPINT2, previously ascribed to congenital sodium diarrhea, as a second gene associated with CTE and report molecular and immunohistochemistry data in 57 CTE patients. Inclusion criteria were early onset diarrhea and intestinal insufficiency with the typical histological CTE abnormalities. The clinical phenotype was registered, the entire coding regions of epcam and SPINT2 sequenced, and immunostaining of EpCAM and SPINT2 performed on intestinal biopsies. An epcam mutation was involved in 41 patients (73 %) who mainly displayed isolated digestive symptoms. Mutations severely affected gene expression since the EpCAM signal on intestinal tissues was either undetectable or low and irregular. Twelve other patients (21 %) carried mutations in SPINT2, and were phenotypically characterized by systematic association with keratitis (p < 10(-4)) and, for half of them, with choanal atresia (p < 10(-4)). Dependency on parenteral nutrition (PN) was comparable in patients with epcam or SPINT2 mutations, but the frequent epcam mutation c.556-14A>G (abnormal splicing) was significantly associated with a better outcome (p = 0.032) with milder PN dependency to weaning in some cases. Finally, four patients (7 %) with isolated digestive symptoms had no detectable epcam or SPINT2 mutation. Two candidate genes, Elf3 and Claudin7, were excluded from this population. Our study allows us to separate CTE patients into at least three genetic classes, each with specific phenotypes. The genetics approach raises the question of the distinction between two congenital enteropathies. Our findings should help improve the diagnosis of CTE, guide toward strategies of long-term PN management, and limit indications for intestinal transplantation to life-threatening PN complications.
    Human Genetics 10/2013; · 4.63 Impact Factor
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    Journal of Hepatology 10/2013; 59:814-829. · 9.86 Impact Factor
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    ABSTRACT: Mucormycosis, an emerging fungal infection in solid organ transplant patients, is mostly located in rhino-orbito-cerebral, pulmonary, and cutaneous areas, or disseminated with poor prognosis. A 4-year-old girl with chronic intestinal pseudo-obstruction syndrome underwent a modified multivisceral transplantation, including half of the stomach, the duodeno-pancreas, the small bowel, and the right colon. On postoperative day 5, a digestive perforation was suspected. Surgical exploration found a small necrotic area on the native stomach, which was externally drained. The next day, massive gastric bleeding occurred. During the emergency laparotomy, 2 hemorrhagic ulcers were found and resected from the transplanted stomach. Pathology and fungal culture showed mucormycosis caused by Lichtheimia (formerly Absidia) ramosa in both the transplanted and native stomach. High-dose intravenous liposomal amphotericin B was immediately started. No other site of fungal infection was found. The child recovered, and 3 years after transplantation, is alive and well, off parenteral nutrition. The originality of this case is the very early presentation after transplantation, the unusual site, and the complete recovery after rapid medico-surgical management. The origin of the fungus and treatment are discussed.
    Transplant Infectious Disease 09/2013; · 1.98 Impact Factor
  • Archives de Pédiatrie. 05/2013; 20(5):550.
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    ABSTRACT: 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.
    American Journal of Clinical Nutrition 02/2013; · 6.50 Impact Factor
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    ABSTRACT: The causes of Reye-like syndrome are not completely understood. Dihydrolipoamide dehydrogenase (DLD or E3) deficiency is a rare metabolic disorder causing neurological or liver impairment. Specific changes in the levels of urinary and plasma metabolites are the hallmark of the classical form of the disease. Here, we report a consanguineous family of Algerian origin with DLD deficiency presenting without suggestive clinical laboratory and anatomopathological findings. Two children died at birth from hepatic failure and three currently adult siblings had recurrent episodes of hepatic cytolysis associated with liver failure or Reye-like syndrome from infancy. Biochemical investigation (lactate, pyruvate, aminoacids in plasma, organic acids in urine) was normal. Histologic examination of liver and muscle showed mild lipid inclusions that were only visible by electron microscopy. The diagnosis of DLD deficiency was possible only after genome-wide linkage analysis, confirmed by a homozygous mutation (p.G229C) in the DLD gene, previously reported in patients with the same geographic origin. DLD and pyruvate dehydrogenase activities were respectively reduced to 25% and 70% in skin fibroblasts of patients and were unresponsive to riboflavin supplementation. In conclusion, this observation clearly supports the view that DLD deficiency should be considered in patients with Reye-like syndrome or liver failure even in the absence of suggestive biochemical findings, with the p.G229C mutation screening as a valuable test in the Arab patients because of its high frequency. It also highlights the usefulness of genome-wide linkage analysis for decisive diagnosis advance in inherited metabolic disorders.
    Molecular Genetics and Metabolism 02/2013; · 2.83 Impact Factor
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    ABSTRACT: Asphyxiating Thoracic Dysplasia (ATD) belongs to the short rib polydactyly group and is characterized by a narrow thorax, short long bones and trident acetabular roof. Other reported features include polydactyly, renal, liver and retinal involvement. To date, mutations in IFT80, DYNC2H1, TTC21B and WDR19 have been reported in ATD. The clinical and molecular heterogeneity leads to difficulties in the evaluation of the long-term prognosis. We investigated 53 ATD cases (23 living cases and 30 fetuses) from 39 families. They benefited from a combined approach of deep phenotyping and IFT80 and DYNC2H1 molecular screening. Among the 23 postnatal cases, pulmonary insufficiency was noted in 60% of cases, with tracheotomy requirement in five cases. Renal and liver diseases occurred respectively in 17% and 22% of cases, whereas retinal alteration was present in 50% of cases aged more than 5 years. We identified DYNC2H1 mutations in 23 families (59%) and IFT80 mutations in two families (5%). However, in six families, only one heterozygote mutation in either IFT80 or DYNC2H1 was identified. Finally, the two genes were excluded in 14 families (36%). We conclude that DYNC2H1 is a major gene responsible for ATD, while IFT80 is rarely involved. The presence of only one mutation in six families and the exclusion of the two genes in 14 families support the involvement of other causal cilia genes. The long-term follow up emphasizes that the pulmonary prognosis is probably less pejorative and retinal involvement more frequent than previously thought.
    Journal of Medical Genetics 02/2013; 50(2):91-8. · 5.70 Impact Factor
  • Cahiers de Nutrition et de Diététique 01/2013; 48:S37.
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    ABSTRACT: Boyer O, Noto C, Patey-Mariaud De Serre N, Gubler M-C, Dechaux M, Goulet O, Niaudet P, Lacaille F. Renal function and histology in children after small bowel transplantation. Abstract:  CKD is a frequent long-term complication after SBTx. CNIs are a well-known factor, but probably not the only cause. We assessed the incidence, risk factors, and severity of CKD in 27 children with SBTx (15 combined liver/SBTx) and prednisone/TAC-based maintenance immunosuppression. Median follow-up was seven yr (3-21). A renal biopsy was performed in 14 patients, 1-18 yr post-SBTx. A reduced GFR was observed in 17 children (63%) during the follow-up with none requiring dialysis. CNI toxicity was observed in 11/14 biopsies, as early as two yr post-transplant, and could occur with a normal mGFR. The dose of TAC was reduced by 50% in 13 patients with CKD and/or significant kidney histological lesions, and six were also given MMF. This led to a significant improvement in renal function: mGFR normalized in eight patients and improved or stabilized in five. No rejection occurred. At last follow-up, 37% had CKD stage 2 and 15% had CKD stage 3. In conclusion, CKD is frequent in children after SBTx and probably multifactorial. Less nephrotoxic immunosuppressive protocols may improve mGFR and should be further considered. The kidney histology helps in designing personalized immunosuppression strategies for patients.
    Pediatric Transplantation 08/2012; · 1.50 Impact Factor
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    ABSTRACT: Sclerosing cholangitis (SC) is a chronic cholestatic disease characterized by inflammation and obliterative fibrosis of the bile ducts, leading to biliary cirrhosis and ultimately to liver failure. Four main clinical forms can be distinguished in children: i) neonatal SC, most probably a genetic disease transmitted by autosomal recessive inheritance; ii) SC associated with strong features of autoimmunity (referred as autoimmune sclerosing cholangitis) with quite good response to immuno-suppression iii) primary SC of unknown etiology (i.e. without features of autoimmunity) and iv) SC secondary to various diseases, including Langerhans cell histiocytosis and immunodeficiencies. Ursodesoxycholic acid is considered the treatment of choice for all forms of SC but without proof of its effectiveness in preventing progression to secondary biliary cirrhosis. In patients with immunodeficiencies, early bone marrow transplantation is the only way to prevent secondary SC. Liver transplantation remains the only validated treatment in children with biliary cirrhosis. Recurrence of SC after liver transplantation has not been clearly demonstrated in children; however, recurrence of Langerhans cell histiocytosis with bile duct injury has been reported. For patients with severe immunodeficiency, a two-step liver then bone marrow transplantation protocol may be proposed.
    Gastroentérologie Clinique et Biologique 05/2012; · 0.80 Impact Factor
  • Florence Lacaille
    Gastroentérologie Clinique et Biologique 05/2012; 36(3):247. · 0.80 Impact Factor
  • Florence Lacaille
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    ABSTRACT: Wilson disease is rare but proteiform, and should be suspected in any child with liver disease and older than 3 years of age. The treatment is very efficient, and must be taken life-long. Fifteen percent of patients with alpha-1-antitrypsin deficiency develop a neonatal jaundice, and 3% a cirrhosis in childhood. There is no specific treatment except liver transplantation. Five percent of cystic fibrosis patients develop a cirrhosis, with a very slow progression. Milder abnormalities are frequent, as well as biliary stones. Liver disease in ciliopathies may be a congenital hepatic fibrosis, with risks of portal hypertension and cholangitis, or a more variable biliary disease. Gilbert disease is frequent and benign. Crigler-Najjar syndrome is rare, severe, and may be an indication for liver or liver-cell transplantation.
    Gastroentérologie Clinique et Biologique 04/2012; 36(3):301-3. · 0.80 Impact Factor

Publication Stats

1k Citations
345.13 Total Impact Points

Institutions

  • 2006–2014
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • Université Paris-Sorbonne - Paris IV
      Lutetia Parisorum, Île-de-France, France
  • 2008–2013
    • Université Paris Descartes
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
  • 2004–2011
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • St. Marien Hospital
      Bonn, North Rhine-Westphalia, Germany