Publications of Eugène MUTIJIMA NZARAMBA
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See detailCancer gastrique diffus héréditaire Série de 8 patients appartenant à une même famille et revue de la littérature
JADOT, Vinciane ULiege; SEGERS, Karin ULiege; Bours, Vincent ULiege et al

in Revue Medicale de Liege (2019), 74(3), 134-138

Hereditary diffuse gastric cancer is a form of gastric cancer associated, in about 40 % of cases, with a germline mutation of the CDH1 gene. The management of patients with a pathogenic mutation of this ... [more ▼]

Hereditary diffuse gastric cancer is a form of gastric cancer associated, in about 40 % of cases, with a germline mutation of the CDH1 gene. The management of patients with a pathogenic mutation of this gene is based on total prophylactic gastrectomy because, until proven otherwise, endoscopic monitoring is insufficient. We report a series of eight patients with pathogenic CDH1 mutation who underwent total prophylactic gastrectomy in our centre. © 2019 Revue Medicale de Liege. All Rights Reserved. [less ▲]

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See detailFacteurs anatomo-cliniques influançant la collecte ganglionnaire dans les pièces de résection chirurgicale pour cancer colorectal
LEDUC, G; BAWIN, Maxime; KESTEMAN, M et al

in Revue Médicale de Liège (2019), 74:10

Dans la stadification de l’adénocarcinome colorectal, le statut ganglionnaire anatomopathologique constitue une information capitale pour le clinicien et doit être défini avec un maximum d’exactitude ... [more ▼]

Dans la stadification de l’adénocarcinome colorectal, le statut ganglionnaire anatomopathologique constitue une information capitale pour le clinicien et doit être défini avec un maximum d’exactitude. L’analyse de la pièce de résection chirurgicale requiert la collecte au sein du méso du plus grand nombre possible de ganglions lymphatiques. Dans cette étude, nous avons analysé une série de facteurs anatomo-cliniques pouvant influencer la collecte ganglionnaire. Un total de 239 patients a été inclus dans notre étude. Les facteurs avec une influence statistiquement significative sur la collecte ganglionnaire (p < 0,05) ont été l’âge et le sexe du patient, la taille de la tumeur primitive, la taille de la pièce d’exérèse, le degré d’activité du chirurgien et le laboratoire d’anatomie pathologique. La présence ou non d’une radiochimiothérapie néoadjuvante n’a pas eu d’impact sur le nombre de ganglions prélevés. Cette étude souligne l’importance de la collecte ganglionnaire au sein des pièces de résection chirurgicale d’un cancer colo-rectal. [less ▲]

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See detailInnovative methodology for the identification of soluble biomarkers in fresh tissues.
Costanza, Brunella ULiege; Turtoi, Andrei ULiege; Bellahcene, Akeila ULiege et al

in Oncotarget (2018), 9(12), 10665-10680

The identification of diagnostic and prognostic biomarkers from early lesions, measurable in liquid biopsies remains a major challenge, particularly in oncology. Fresh human material of high quality is ... [more ▼]

The identification of diagnostic and prognostic biomarkers from early lesions, measurable in liquid biopsies remains a major challenge, particularly in oncology. Fresh human material of high quality is required for biomarker discovery but is often not available when it is totally required for clinical pathology investigation. Hence, all OMICs studies are done on residual and less clinically relevant biological samples. Here after, we present an innovative, simple, and non-destructive, procedure named EXPEL that uses rapid, pressure-assisted, interstitial fluid extrusion, preserving the specimen for full routine clinical pathology investigation. In the meantime, the technique allows a comprehensive OMICs analysis (proteins, metabolites, miRNAs and DNA). As proof of concept, we have applied EXPEL on freshly collected human colorectal cancer and liver metastases tissues. We demonstrate that the procedure efficiently allows the extraction, within a few minutes, of a wide variety of biomolecules holding diagnostic and prognostic potential while keeping both tissue morphology and antigenicity unaltered. Our method enables, for the first time, both clinicians and scientists to explore identical clinical material regardless of its origin and size, which has a major positive impact on translation to the clinic. [less ▲]

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See detailComment je traite... les cancers localises de l'oesophage. Etat actuel des donnees et strategie therapeutique. 2eme partie : l'interet des approches multimodales avec ou sans chirurgie.
VAN DAELE, Daniel ULiege; Honoré, Pierre ULiege; COLLIGNON, Joëlle ULiege et al

in Revue Médicale de Liège (2017), 72(4), 168-174

In recent years, the treatment of esophagus cancer has been completely changed, thus competing the dogma of surgery as the cornerstone treatment. Multimodality treatments as radio-chemotherapy directly ... [more ▼]

In recent years, the treatment of esophagus cancer has been completely changed, thus competing the dogma of surgery as the cornerstone treatment. Multimodality treatments as radio-chemotherapy directly followed by surgery, or delayed surgery, significantly improve patient survival compared to surgery alone. Neoadjuvant radiochemotherapy is associated with a higher complete pathologic response rate and improved survival compared to chemotherapy alone. Immediate surgery after radio-chemotherapy is challenged for patients who present a complete clinical response, especially in case of squamous cell carcinoma. Indeed, systematic resection is associated with a significant postoperative mortality rate and has not proven any survival advantage in complete clinical responders as opposed to delayed resection in case of locally persistent or recurrent disease. In squamous cell carcinoma, this could lead to organ preservation, thus avoiding the mortality and durable functional impairment of esophagectomy. This review will discuss the positioning of the multimodality treatment strategy with neoadjuvant radiochemotherapy and chemotherapy and also the strategy of organ preservation. [less ▲]

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See detailComment je traite... les cancers localises de l'oesophage. Etat actuel des donnees et strategie therapeutique. 1ere partie : le point sur les approches chirurgicales et non chirurgicales.
VAN DAELE, Daniel ULiege; Honoré, Pierre ULiege; COLLIGNON, Joëlle ULiege et al

in Revue Médicale de Liège (2017), 72(2), 58-63

Esophageal cancers represent a highly heterogeneous entity mixing two different tumour types : AdenoCarcinoma (ADC) and Squamous Cell Carcinoma (SSC). Developing in the same organ, they are very often ... [more ▼]

Esophageal cancers represent a highly heterogeneous entity mixing two different tumour types : AdenoCarcinoma (ADC) and Squamous Cell Carcinoma (SSC). Developing in the same organ, they are very often considered as a unique pathology and, consequently, the same therapeutic strategy is indiscriminately applied. Esophageal cancer treatments are particularly complex and require a multidisciplinary approach. Despite impressive advances in the tumour statidifaction, surgery, radiotherapy and chemotherapy, the overall prognosis remains grim even at an early stage of the disease. In order to improve the treatment of esophageal cancers and the patientaeuros survival, we need to consider that ADC and SCC represent two different pathologies requiring specific therapeutic strategies. This review in two parts will present recent data from clinical trials under the scope of tumour histology to set up dedicated therapeutic strategies. In this first part, we explain the restricted role of surgical resection, the prognostic factors and the results of exclusive combined chemotherapy and radiation in localized esophageal cancer. [less ▲]

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See detailWeekly cisplatin with radiotherapy for locally advanced head and neck squamous cell carcinoma.
SAUTOIS, Brieuc ULiege; SCHROEDER, Hélène ULiege; MARTIN, Marie ULiege et al

in Journal of Balkan Union of Oncology (2016), 21(4), 979-988

Background Although commonly used for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC) concomitant radio-chemotherapy (RT-CT) with weekly cisplatin has not been definitely ... [more ▼]

Background Although commonly used for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC) concomitant radio-chemotherapy (RT-CT) with weekly cisplatin has not been definitely studied. We conducted a single centre retrospective study with the aim to evaluate efficacy and acute toxicity of definitive concomitant RT-CT with 40 mg/m² weekly cisplatin in patients with locally advanced HNSCC with a particular emphasis on radiotherapy modality (conventional or accelerated) and dose of cisplatin delivered. Method One hundred and twelve consecutive patients were included. They were given cisplatin 40 mg/m²/week concomitantly with conventionally fractionated (CFRT) (N = 33) or accelerated (ART) (N = 79) radiotherapy. Results Radiotherapy was delivered according to the treatment plan in 104 patients and full dose was given to 107 patients. A median cumulative cisplatin dose of 240 mg/m² was delivered to patients treated with CFRT and of 200 mg/m² to those treated with ART. Overall complete response rate was 81.3%. With a median follow up of 38.4 months, median overall survival was 75 months, not influenced by radiotherapy type or cisplatin dose received. The most clinically significant grade 3 or 4 acute toxicities were stomatitis (35.7%), neutropenia (25%), anemia (12.5%) and acute kidney injury (5.4%). Conclusion Our study shows that a median cumulative dose of 200 mg/m² cisplatin can be safely delivered using a weekly regimen to patients treated with concomitant radiotherapy (CFRT or ART). Efficacy results and toxicity compare favourably with those described with triweekly cisplatin RT-CT suggesting that a randomized comparison should be undertaken. [less ▲]

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See detailCancers du pancréas exocrine
DURAN, Unal ULiege; brisbois, d; marterne, R. et al

in Encyclopédie Médico-Chirurgicale (2016)

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See detailEXPEL: A Novel Non-Destructive Method for Mining Soluble Tumor Biomarkers
Costanza, Brunella ULiege; Blomme, Arnaud ULiege; Bellahcene, Akeila ULiege et al

in Acta Gastro-Enterologica Belgica (2016), 79(1), 11

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See detailExpel: a novel non-destructive method for mining soluble tumor biomarkers
Costanza, Brunella ULiege; Blomme, Arnaud ULiege; MUTIJIMA NZARAMBA, Eugène ULiege et al

in Acta Gastro-Enterologica Belgica (2015, March), 78(1), 13

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See detail18F-FPRGD2 PET/CT imaging of integrin αvβ3 in renal carcinomas: Correlation with histopathology
WITHOFS, Nadia ULiege; SIGNOLLE, NICOLAS; SOMJA, Joan ULiege et al

in Journal of Nuclear Medicine (2015)

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See detailOrganized Proteomic Heterogeneity in Colorectal Cancer Liver Metastases and Implications for Therapies
Turtoi, Andrei ULiege; Blomme, Arnaud ULiege; Debois, Delphine ULiege et al

in Hepatology (2014), 59(3), 924-934

Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems ... [more ▼]

Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis dis- played increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demon- strate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. Conclusion: The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of target- able antigens. [less ▲]

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See detailUnusual presentation of osteopoikilosis.
Simoni, P.; Denut, J.; Ben Mustapha, S. et al

in JBR-BTR (2013), 96(6), 386-7

We present a case of osteopoikilosis in a 74-year-old woman with hip pain, presenting multiple osteoblastic lesions of the axial skeleton including an osteoblastic large lesion of her left femur. The ... [more ▼]

We present a case of osteopoikilosis in a 74-year-old woman with hip pain, presenting multiple osteoblastic lesions of the axial skeleton including an osteoblastic large lesion of her left femur. The imaging findings on X-rays and computed tomography are provided along with the discussion of the differential diagnosis on the basis of the recent literature. [less ▲]

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See detailNasal cancer in the pediatric population.
MAUDOUX, Audrey ULiege; LEONARD, B; DETREMBLEUR, Nancy ULiege et al

Poster (2012, March)

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See detailNovel comprehensive approach for accessible biomarker identification and absolute quantification from precious human tissues
Turtoi, Andrei ULiege; Dumont, Bruno ULiege; Greffe, Yannick et al

in Journal of Proteome Research (2011), 10(7), 3160-82

The identification of specific biomarkers obtained directly from human pathological lesions remains a major challenge, because the amount of tissue available is often very limited. We have developed a ... [more ▼]

The identification of specific biomarkers obtained directly from human pathological lesions remains a major challenge, because the amount of tissue available is often very limited. We have developed a novel, comprehensive, and efficient method permitting the identification and absolute quantification of potentially accessible proteins in such precious samples. This protein subclass comprises cell membrane associated and extracellular proteins, which are reachable by systemically deliverable substances and hence especially suitable for diagnosis and targeted therapy applications. To isolate such proteins, we exploited the ability of chemically modified biotin to label ex vivo accessible proteins and the fact that most of these proteins are glycosylated. This approach consists of three successive steps involving first the linkage of potentially accessible proteins to biotin molecules followed by their purification. The remaining proteins are then subjected to glycopeptide isolation. Finally, the analysis of the nonglycosylated peptides and their involvement in an in silico method increased the confident identification of glycoproteins. The value of the technique was demonstrated on human breast cancer tissue samples originating from 5 individuals. Altogether, the method delivered quantitative data on more than 400 potentially accessible proteins (per sample and replicate). In comparison to biotinylation or glycoprotein analysis alone, the sequential method significantly increased the number (≥30% and ≥50% respectively) of potentially therapeutically and diagnostically valuable proteins. The sequential method led to the identification of 93 differentially modulated proteins, among which several were not reported to be associated with the breast cancer. One of these novel potential biomarkers was CD276, a cell membrane-associated glycoprotein. The immunohistochemistry analysis showed that CD276 is significantly differentially expressed in a series of breast cancer lesions. Due to the fact that our technology is applicable to any type of tissue biopsy, it bears the ability to accelerate the discovery of new relevant biomarkers in a broad spectrum of pathologies. [less ▲]

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See detailCancer du sein: importance de la nomenclature anatomo-pathologique
BLETARD, Noëlla ULiege; DETREMBLEUR, Nancy ULiege; SCAGNOL, Irène ULiege et al

in Revue Médicale de Liège (2011), 66(5-6), 261-4

The breast pathology includes a large array of entities for which macroscopic and microscopic analysis remains fundamental. Tissue and cell morphology allows in most cases the distinction between benign ... [more ▼]

The breast pathology includes a large array of entities for which macroscopic and microscopic analysis remains fundamental. Tissue and cell morphology allows in most cases the distinction between benign or malignant tumours and therefore provides the clinicians with essential information for the therapeutic strategy. In the Pathology laboratory, immunohistochemistry and molecular biology have improved the specificity of the diagnosis and have introduced new prognostic and predictive markers for tumour management. The last edition of the WHO classification, released in 2003, distinguishes 21 varieties of invasive carcinoma and 2 categories of intraepithelial neoplasia based on the morphology and immunohistochemical profile. Other diseases can affect the breast, although much less frequently, such as Paget’s disease of the nipple, phyllode tumours, sarcomas, lymphomas... These diseases will not be reviewed here. [less ▲]

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See detailHigh incidence of high-risk HPV in benign and malignant lesions of the larynx.
Duray, Anaelle; Descamps, Geraldine; Arafa, Mohammad et al

in International Journal of Oncology (2011), 39(1), 51-9

The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 ... [more ▼]

The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 type-specific PCR. Paraffin-embedded samples from LBL (n=39) and LSCC patients (n=67) were evaluated for the presence of HPV DNA by GP5+/GP6+ consensus PCR and E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. In LSCCs, immunohistochemical staining of p16, p53 and EGFR was also assessed. The E6/E7 type-specific PCR showed that 44 out of 59 LSCC patients (i.e., 75%) had high-risk (hr) HPV types and that 27 out of 35 LBL patients (i.e., 77%) had hrHPV types. HPV-16 viral load was significantly higher in LSCC than in LBL patients (p<10-6). The presence of hrHPV DNA did not correlate with the proportion of disease-free patients. Comparable levels of p16, p53 and EGFR expression were observed in the hrHPV+ tumor group (100% p16+, 56% p53+ and 97% EGFR+) and in the HPV- or low-risk (lr) HPV+ tumor group (92% p16+, 66% p53+ and 100% EGFR+). A very high prevalence of oncogenic HPV-16 was found in a series of benign and malignant laryngeal lesions. LSCC appears to be characterized by an active hrHPV infection. In LSCCs, the hrHPV+ subgroup had a similar prognosis (in terms of risk of recurrence) as the HPV- subgroup. [less ▲]

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