Christine Sempoux

Pathologie Institut Enge, Zürich, Zurich, Switzerland

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Publications (224)1060.94 Total impact

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    ABSTRACT: To evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO compatibility, and impact of maternal donation on graft acceptance. LDLT and ABO-mismatched transplantation constitute feasible options to alleviate organ shortage in children. Vascular complications of portal hypoplasia in biliary atresia (BA) and acute rejection (AR) are still major concerns in this field. Data from 250 pediatric LDLT recipients, performed at Cliniques Universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively. Results were analyzed according to ABO matching and PV complications. Uni- and multivariate analyses were performed to study the impact of immunosuppression, sex matching, and maternal donation on AR rate. Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft loss nor vascular rejection, nor hemolysis, was encountered in the ABO nonidentical patients (n = 58), provided pretransplant levels of relevant isoagglutinins were below 1/16. In BA recipients, the rate of PV complications was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and to jump graft interposition (26.9%; P = 0.027). In parental donation, maternal grafts were associated with higher 1-year AR-free survival (55.2%) than paternal grafts (39.8%; P = 0.041), but only in BA patients. LDLT, including ABO-mismatched transplantation, constitutes a safe and efficient therapy for liver failure in children. In BA patients with PV hypoplasia, portoplasty seems to constitute the best technique for PV reconstruction. Maternal donation might be a protective factor for AR.
    Annals of Surgery 01/2015; DOI:10.1097/SLA.0000000000001094 · 7.19 Impact Factor
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    Human pathology 12/2014; DOI:10.1016/j.humpath.2014.10.029 · 2.81 Impact Factor
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    ABSTRACT: Hepatocellular adenomas are rare benign nodules developed mainly in women taking oral contraceptives. They are solitary or multiple. Their size is highly variable. There is no consensus in the literature for their management except that once their size exceeds 5cm nodules are taken out to prevent 2 major complications: bleeding and malignant transformation. There are exceptions particularly in men where it is recommended to remove smaller nodules. Since the beginning of this century, major scientific contributions have unveiled the heterogeneity of the disease. HCA are composed of four major subtypes. HNF1A (coding for hepatocyte nuclear factor 1a) inactivating mutations (H-HCA); inflammatory adenomas (IHCA); the β-catenin-mutated HCAs (β-HCA) and unclassified HCA (UHCA) occurring in 30-40%, 40-50%, 10-15% and 10% of all HCA, respectively. Half of β-HCAs are also inflammatory (β-IHCA). Importantly, β-catenin mutations are associated with a high risk of malignant transformation. HCA subtypes can be identified on liver tissue, including biopsies using specific immunomarkers with a good correspondence with molecular data. Recent data has shown that TERT promoter mutation was a late event in the malignant transformation of β-HCA, β-IHCA. Furthermore, in addition to β-catenin exon 3 mutations, other mutations do exist (exon 7 and 8) with a lower risk of malignant transformation. With these new scientific informations, we have the tools to better know the natural history of the different subtypes, in terms of growth, disappearance, bleeding, malignant transformation and to investigate HCA in diseased livers (vascular diseases, alcoholic cirrhosis). A better knowledge of HCA should lead to a more rational management of HCA. This can be done only if the different subspecialties, including hepatologists, liver pathologists, radiologists and surgeons work altogether in close relationship with molecular biologists. It is a long way to go. Copyright © 2014. Published by Elsevier Masson SAS.
    Gastroentérologie Clinique et Biologique 11/2014; DOI:10.1016/j.clinre.2014.10.003 · 1.98 Impact Factor
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    ABSTRACT: Background: Solitary extramedullary plasmacytoma (SEP) is a rare malignant neoplasm arising from plasma cells. SEP mostly occurs in the upper respiratory tract. Thyroid gland is rarely affected (<78 cases). Methods/results: We describe the case of a 78-year-old woman presenting a rapidly enlarging palpable thyroid mass. Neck computed tomography scan showed enlargement of both thyroid lobes. Laboratory tests were normal, including serum protein level with no monoclonal gamma globulin peak. Cytology was suspicious for lymphoma. Biopsy showed an infiltrating neoplasm composed of atypical tumor cells with abundant cytoplasm and eccentric nuclei. These revealed diffuse immunoreactivity for CD138 and predominant staining for immunoglobulin kappa light chains. Clinical workup for multiple myeloma was negative. Conclusions: SEP should be considered in the differential diagnosis of a rapidly enlarging thyroid nodule and be distinguished from involvement of thyroid in multiple myeloma, mucosa-associated lymphoid tissue lymphoma, plasma cell granuloma and medullary carcinoma. Clinical correlation and immunohistochemistry are crucial in avoiding pitfalls.
    11/2014; 70(2):2295333714Y0000000095. DOI:10.1179/2295333714Y.0000000095
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    ABSTRACT: Objective: To investigate the safety of minimal immunosuppression (IS) in liver transplantation (LT). Background: The lack of long-term follow-up studies, including pathologic data, has led to a protean handling of IS in LT. Methods: Between February 2000 and September 2004, 156 adults were enrolled in a prospective, randomized, double-blind, placebo-controlled minimization trial comparing tacrolimus placebo (TAC-PLAC) and TAC short-term steroid (TAC-STER) IS. All patients had a minimum clinical, biochemical, and histological follow-up of 5 years. Results: Five-year actual patient and graft survival rates in TAC-PLAC and TAC-STER groups were 78.1% and 82.1% (P = 0.89) and 74.2% and 76.9% (P = 0.90), respectively. Five-year biopsies were available in 112 (89.6%) of 125 survivors. Twelve patients refused a biopsy because of their excellent evolution; tissue material was insufficient in 1 patient; 11 had normal liver tests; and 2 patients had developed alcoholic and secondary biliary cirrhosis. Histology was normal in 44 (39.3%) patients; 35 (31.3%) had disease recurrence. The remaining biopsies showed nonspecific chronic hepatitis (14.3%), mild inflammatory infiltrates (10.7%), and steatosis (3.5%). All findings were equally distributed between both groups. In each group, 3 patients (4.8%) presented with acute cellular rejection after the first year and only 1 (0.9%) TAC-PLAC patient developed chronic rejection after IS withdrawal because of pneumonitis. Arterial hypertension, diabetes mellitus, renal insufficiency, hypercholesterolemia, gout, and obesity were equally low in both groups. Conclusions: Excellent long-term results can be obtained under minimal IS and absence of steroids. TAC-based monotherapy is feasible in most adult liver recipients until 5 years of follow-up.
    Annals of Surgery 11/2014; 260(5):886-892. DOI:10.1097/SLA.0000000000000969 · 7.19 Impact Factor
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    ABSTRACT: The transcription factor SOX9 was recently shown to stimulate ductal gene expression in pancreatic acinar-to-ductal metaplasia and to accelerate development of premalignant lesions preceding pancreatic ductal adenocarcinoma (PDAC). Here, we investigate how SOX9 operates in pancreatic tumourigenesis.
    Gut 10/2014; DOI:10.1136/gutjnl-2014-307075 · 13.32 Impact Factor
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    ABSTRACT: Our goal was to optimize the radiosensitizing potential of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, when given concomitantly with preoperative radiotherapy in KRAS wild-type locally advanced rectal cancer (LARC). Based on pre-clinical studies conducted by our group, we designed a phase II trial in which panitumumab (6 mg/kg/q2 weeks) was combined with preoperative radiotherapy (45 Gy in 25 fractions) to treat cT3-4/N + KRAS wild-type LARC. The primary endpoint was complete pathologic response (pCR) (H0 = 5 %, H1 = 17 %, α = 0.05, β = 0.2). From 19 enrolled patients, 17 (89 %) were evaluable for pathology assessment. Although no pCR was observed, seven patients (41 %) had grade 3 Dworak pathological tumor regression. The regimen was safe and was associated with 95 % of sphincter-preservation rate. No NRAS, BRAF, or PI3KCA mutation was found in this study, but one patient (5 %) showed loss of PTEN expression. The quantification of plasma EGFR ligands during treatment showed significant upregulation of plasma TGF-α and EGF following panitumumab administration (p < 0.05). At surgery, patients with important pathological regression (grade 3 Dworak) had higher plasma TGF-α (p = 0.03) but lower plasma EGF (p = 0.003) compared to those with grade 0-2 Dworak. Our study suggests that concomitant panitumumab and preoperative radiotherapy in KRAS wild-type LARC is feasible and results in some tumor regression. However, pCR rate remained modest. Given that the primary endpoint of our study was not reached, we remain unable to recommend the use of panitumumab as a radiosensitizer in KRAS wild-type LARC outside a research setting.
    Targeted Oncology 10/2014; DOI:10.1007/s11523-014-0342-9 · 3.46 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):LB-73-LB-73. DOI:10.1158/1538-7445.AM2014-LB-73 · 9.28 Impact Factor
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    ABSTRACT: Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tumoral resistance to immune rejection. In humans, constitutive expression of IDO1 has been observed in several tumor types. However, a comprehensive view of its expression in normal and tumor tissues is still required in order to anticipate the risks and potential benefits of IDO1 inhibitors. Using a new validated monoclonal antibody to human IDO1, we performed an extensive immunohistochemical analysis of IDO1 expression in normal and tumor tissues. In normal tissues, IDO1 was expressed by endothelial cells in placenta and lung, and by epithelial cells in the female genital tract. It was also expressed in lymphoid tissues, in cells with a phenotype of mature dendritic cells (CD83+, DC-LAMP+, langerin-, CD123-, CD163-) distinct from plasmacytoid dendritic cells. Importantly, IDO1-expressing dendritic cells were not enriched in tumor-draining lymph nodes, in contrast with previously reported findings. IDO1-expressing cells were observed in a large fraction (505/866, 58%) of human tumors. These cells were tumor cells, endothelial cells and stromal cells, in proportions that varied depending on the tumor type. Tumors showing the highest proportions of IDO1-immunolabelled samples included carcinomas of endometrium and cervix, followed by kidney, lung, and colon. This hierarchy was confirmed by gene expression data mined from the TCGA database. Our observations indicate that the relevant IDO1 for tumoral immune escape is expressed in the tumor itself rather than in its draining lymph node. They also help selecting the most likely tumors to benefit from targeted therapy with IDO1 inhibitors.
    09/2014; 3(2). DOI:10.1158/2326-6066.CIR-14-0137
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    ABSTRACT: This practical atlas aims to help liver and non liver pathologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocellular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for paraffin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glutamine synthase and according to the above results additional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocellular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated.
  • Anne Druez, Elizaveta Kim, Christine Sempoux, Pierre Deprez
    06/2014; 02(02):E124-E125. DOI:10.1055/s-0034-1377174
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    ABSTRACT: We report here the case of a 56-year-old man with well-documented cardiac light chain amyloidosis successfully imaged with F-flutemetamol PET/CT in 2011. A matched pair healthy volunteer was imaged in the same conditions, and no specific heart uptake could be detected. The present report suggests the potential benefit of this new pharmaceutical in this indication, as it has been recently reported for C-Pittsburgh compound B, but with the main advantage to benefit from the more practical half-life of F. Further prospective trials would, however, be required to define the potential impact of F-flutemetamol PET/CT in cardiac amyloidosis.
    Clinical Nuclear Medicine 06/2014; DOI:10.1097/RLU.0000000000000492 · 2.86 Impact Factor
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    ABSTRACT: Progressive liver allograft fibrosis (LAF) is well known to occur long term, as shown by its high prevalence in late posttransplant liver biopsies (LBs). To evaluate the influence of clinical variables and immunosuppression on LAF progression, LAF dynamic was assessed in 54 pediatric liver transplantation (LT) recipients at 6 months, 3 and 7 years post-LT, reviewing clinical, biochemical data and protocol LBs using METAVIR and the liver allograft fibrosis score, previously designed and validated specifically for LAF assessment. Scoring evaluations were correlated with fibrosis quantification by morphometric analysis. Progressive LAF was found in 74% of long-term patients, 70% of whom had unaltered liver enzymes. Deceased grafts showed more fibrosis than living-related grafts (p = 0.0001). Portal fibrosis was observed in correlation with prolonged ischemia time, deceased grafts and lymphoproliferative disease (p = 0.001, 0.006 and 0.012, respectively). Sinusoidal fibrosis was correlated with biliary complications (p = 0.01). Centrilobular fibrosis was associated with vascular complications (p = 0.044), positive autoantibodies (p = 0.017) and high gamma-globulins levels (p = 0.028). Steroid therapy was not associated with reduced fibrosis (p = 0.83). LAF could be viewed as a dynamic process with mostly progression along the time. Peri- and post-LT-associated factors may condition fibrosis development in a specific area of the liver parenchyma.
    American Journal of Transplantation 06/2014; 14(7). DOI:10.1111/ajt.12740 · 6.19 Impact Factor
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    ABSTRACT: The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection. Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined. The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of > 5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis. Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.
    Annals of Surgical Oncology 06/2014; 21(12). DOI:10.1245/s10434-014-3828-x · 3.94 Impact Factor
  • Gastrointestinal Endoscopy 05/2014; 79(5):AB450. DOI:10.1016/j.gie.2014.02.649 · 4.90 Impact Factor
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    ABSTRACT: Non-alcoholic fatty liver (steatosis) and steatohepatitis (NASH) are hepatic complications of metabolic syndrome. Endoplasmic reticulum (ER) stress is proposed as a crucial disease mechanism in obese and insulin resistant animals (such as ob/ob mice) with simple steatosis but its role in NASH remains controversial. We therefore evaluated the role of ER stress as a disease mechanism in foz/foz mice, which develop both the metabolic and the histological features that mimic human NASH. We explored ER stress markers in the liver of foz/foz mice in response to high-fat diet (HFD) after several time points. We then evaluated the effect of treatment with ER stress inducer tunicamycin, or conversely with ER protectant tauro-ursodeoxycholic acid (TUDCA) on the metabolic and hepatic features. Foz/foz mice are obese, glucose intolerant and develop NASH characterized by steatosis, inflammation, ballooned hepatocytes and apoptosis from 6 weeks of HFD feeding. This was not associated with activation of the upstream unfolded protein response (phospho-eIF2α, IRE1α activity, spliced Xbp1). Activation of JNK and up-regulation of Atf4 and Chop transcripts were however compatible with a "pathologic" response to ER stress. We tested it by intervention experiments. Induction of chronic ER stress failed to worsen obesity, glucose intolerance and NASH pathology in HFD-fed foz/foz mice. In addition, ER protectant TUDCA, although reducing steatosis, failed to improve glucose intolerance, hepatic inflammation and apoptosis in HFD-fed foz/foz mice. These results show that signals driving hepatic inflammation, apoptosis and insulin resistance are independent of ER stress in obese, diabetic mice with steatohepatitis.
    Clinical Science 04/2014; DOI:10.1042/CS20140026 · 5.63 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S149-S150. DOI:10.1016/S0168-8278(14)60415-3 · 10.40 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S176. DOI:10.1016/S0168-8278(14)60492-X · 10.40 Impact Factor
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    ABSTRACT: To investigate the activity and expression of EAAT2 glutamate transporter in both in vitro and in vivo models of cholestasis. This study was conducted on human hepatoblastoma HepG2 cell cultures, the liver of bile duct ligated rats and human specimens from cholestatic patients. EAAT2 glutamate transporter activity and expression were analyzed using a substrate uptake assay, immunofluorescence, reverse transcription-polymerase chain reaction, and immunohistochemistry, respectively. In HepG2 cells, cholestasis was mimicked by treating cells with the protein kinase C activator, phorbol 12-myristate 13-acetate. Under such conditions, EAAT2 transporter activity was decreased both at the level of substrate affinity and maximal transport velocity. The decreased uptake was correlated with intracellular translocation of EAAT2 molecules as demonstrated using immunofluorescence. In the liver of bile duct ligated rats, an increase in EAAT2 transporter protein expression in hepatocytes was demonstrated using immunohistochemistry. The same findings were observed in human liver specimens of cholestasis in which high levels of γ-glutamyl transpeptidase were documented in patients with biliary atresia and progressive familial intrahepatic cholestasis type 3. This study demonstrates the alteration in glutamate handling by hepatocytes in liver cholestasis and suggests a potential cross-talk between glutamatergic and bile systems.
    World Journal of Gastroenterology 02/2014; 20(6):1554-64. DOI:10.3748/wjg.v20.i6.1554 · 2.43 Impact Factor
  • Gastroentérologie Clinique et Biologique 02/2014; 38(3). DOI:10.1016/j.clinre.2014.01.001 · 1.98 Impact Factor

Publication Stats

4k Citations
1,060.94 Total Impact Points

Institutions

  • 2014
    • Pathologie Institut Enge
      Zürich, Zurich, Switzerland
  • 1997–2014
    • Catholic University of Louvain
      • • Institute of Experimental and Clinical Research (IREC)
      • • Laboratory of Hepatogastroenterology
      • • Department of Radiology and Medical Imaging - RAIM
      • • School of Medicine
      Лувен-ла-Нев, Walloon, Belgium
  • 1996–2014
    • Cliniques Universitaires Saint-Luc
      • • Division of Pathology
      • • Cancer Centre
      • • Department of Clinical Biology and Pathology
      Bruxelles, Brussels Capital Region, Belgium
  • 2010
    • Clinique Saint-Luc, Bouge
      Namen, Walloon Region, Belgium
  • 1997–1999
    • University Hospital Brussels
      Bruxelles, Brussels Capital Region, Belgium