[The contribution of «Télévie¼ and the «Léon Fredericq Foundation¼ to the fundamental cancer research in Liège]. / La contribution de Télévie et de la Fondation Léon Fredericq à la recherche fondamentale en cancérologie à Liège.

Télévie and the Léon Fredericq Foundation support many research projects in the CHU of Liège and the ULiège. This paper summarizes some projects aiming at a better knowledge of the basic mechanisms leading to cancer development, of the immune defenses against tumours, of specific characteristics of some cancer types and, finally, of strategies for improving quality of life of patients whose fertility has been threatened by anti-cancer treatments.

Le Télévie et la Fondation Léon Fredericq soutiennent de nombreux projets de recherche cancérologique au CHU de Liège et à l'ULiège. Cet article résume quelques projets de recherche qui concernent une meilleure connaissance des mécanismes fondamentaux qui sous-tendent la formation des cancers, des moyens de défense de l'organisme contre ces maladies, des caractéristiques particulières de quelques types de cancers et, enfin, de stratégies visant à améliorer la qualité de vie des patientes cancéreuses en leur rendant la fertilité menacée par les traitements anti-cancéreux.

[The Leon Fredericq Foundation against COVID-19 in Liege]. / La Fondation Léon Fredericq contre la COVID-19 à Liège.

The Leon Fredericq Foundation gives support to the clinicians and the scientists of the Uliege and of the CHU of Liege in order to push back the frontiers of biomedical science and to contribute to improve the care and cure of patients. Since the outbreak due to COVID-19, the Foundation has given out a call for donations in order to support urgent procedures for taking care of COVID-19 suffering patients. Furthermore, by raising important financial means, the Foundation has selected thirteen research projects aiming at a better understanding of the SARS-CoV-2-induced disease.

La Fondation Léon Fredericq soutient les médecins et les chercheurs de l'ULiège et du CHU de Liège pour faire reculer les frontières de la connaissance et contribuer à améliorer les soins aux patients. Dès le début de la crise due à la COVID-19, elle a lancé un appel aux dons visant à permettre au CHU de prendre des mesures d'urgence pour la prise en charge des patients atteints de cette maladie. En outre, en mobilisant des moyens financiers importants, elle a sélectionné treize projets de recherche visant à mieux comprendre les conséquences d'une infection par le SARS-CoV-2.

[Clinical case of the month. Intrapulmonary lung sequestration diagnosed in an adult]. / Le cas clinique du mois. A propos d'un cas de séquestration pulmonaire intralobaire diagnostiqué à l'âge adulte.

Pulmonary sequestration is a rare congenital lung malformation characterized by an abnormal segment of bronchopulmonary tissue supplied by aberrant systemic arteries. Due to the non-specific symptomatology, the diagnosis can be missed. Imaging is the cornerstone of the diagnosis. Complete surgical resection provides the definitive treatment. We report a case of pulmonary sequestration associated with an asymptomatic aspergillosis presenting during adulthood and describe briefly the epidemiology, embryology, histology, imaging and surgical treatment of this congenital abnormality.

[Cancer stem cells]. / Les cellules souches cancéreuses.

In tumours, a significant fraction of neoplastic cells are engaged in the cell cycle (growth fraction) and are therefore targets for radiation therapy and chemotherapy. Unfortunately, in most disseminated cancers, such treatments cannot lead to complete cure. Many different mechanisms have been described to explain this resistance. The hypothesis of the existence of "cancer stem cells "has been recently proposed. Indeed, the tumour would contain a small subpopulation of cancer cells displaying the phenotypical characteristics of multipotential stem cells. Since such cells display different signalling pathways compared with more differentiated cells, this might explain at least partially the resistance to treatments. Chronic myeloid leukaemia is a good model in favour of cancer stem cells, but the presence of such cells in all types of cancers is still a matter of debate. Several questions emerge: is the multipotential stem cell, the cell of origin of cancer? What is the relevance of the cancer stem cell paradigm for understanding cancer cell biology and to envision new therapeutic, hopefully curative, therapies? The case of chronic myeloid leukaemia is used to discuss these questions.

[Fish and chips]. / Fish and chips.

Academic hospital laboratories should offer patients the possibility to have the most accurate diagnosis by the development of new analyses, such as molecular biology tests including FISH (Fluorescent In Situ Hybridization) and chips (microarrays,...). The purpose of this article is to describe the principles and the potential applications of these techniques.

Budd-Chiari syndrome complicating hepatic sarcoidosis: definitive treatment by liver transplantation: a case report.

Sarcoidotic involvement of the liver is frequent, albeit uncommonly symptomatic. Severe complications are rare, but may seldom require liver transplantation. Budd-Chiari syndrome has been described in a few patients with hepatic sarcoidosis. Herein we have reported the case of a young woman suffering from hepatic sarcoidosis who developed severe cholestasis and chronic Budd-Chiari syndrome. She successfully underwent orthotopic liver transplantation (OLT) and is asymptomatic with normal liver function at 3 years follow-up. Histopathological assessment of the liver explant demonstrated a florid granulomatous process, with involvement of the large intrahepatic veins, providing an anatomical basis for the vascular flow disturbances. This case adds further evidence that liver transplantation may be the curative treatment for complicated sarcoidotic liver disease.

[Neuroendocrine tumors of the appendix]. / Tumeurs neuroendocrines appendiculaires: à propos d'un cas, de l'histologie à la thérapeutique.

An 19-year-old woman was admitted for acute appendicitis. The histological study of the appendix revealed a tubular variant of endocrine carcinoma of the appendix. Neuroendocrine tumors ("NETs") of the appendix are rare tumors which are usually detected incidentally, affecting 0.3% to 0.9% of appendectomies. Depending on their size, but also on some other factors, including histologic type, these tumors will require specific treatment; sometimes appendectomy will not be sufficient.

High frequency of RASSF1A and RARb2 gene promoter methylation in morphologically normal endometrium adjacent to endometrioid adenocarcinoma.

AIMS: To identify a DNA methylation signature of endometrioid carcinoma of the endometrium (EEC) in the early stages of endometrial carcinogenesis. METHODS AND RESULTS: Archival biopsy specimens of 39 EECs, 14 cases of atypical hyperplasia (AH), 11 histologically normal endometrial tissues adjacent to EECs and 24 normal control endometrial samples were retrieved. The cases were tested by quantitative methylation-specific polymerase chain reaction with primers hybridizing in the promoter regions of five genes frequently methylated in human cancer (RASSF1A, RARb2, P16, MGMT and GSTPi). Twenty-nine of 39 (74%) EECs and 7/14 (50%) AHs were methylated for the RASSF1A gene, whereas 17/39 (44%) EECs and 6/14 (43%) AHs were positive for the methylation of the RARb2 gene. No significant results were obtained for the other genes (P16, MGMT and GSTPi). Interestingly, 4/11 (36%) and 6/11 (55%) histologically normal endometrial tissues adjacent to EEC showed, respectively, RASSF1A and RARb2 gene methylation. Furthermore, these 11 specimens were microsatellite stable and showed similar proliferative, cell cycle and apoptotic mean labelling indices as the normal endometrial control tissues. CONCLUSIONS: Promoter region methylation of RASSF1A and RARb2 genes is an early event in endometrial carcinogenesis.

Innate lymphocyte and dendritic cell cross-talk: a key factor in the regulation of the immune response.

Dendritic cells (DC) are specialized in the presentation of antigens and the initiation of specific immune responses. They have been involved recently in supporting innate immunity by interacting with various innate lymphocytes, such as natural killer (NK), NK T or T cell receptor (TCR)-gammadelta cells. The functional links between innate lymphocytes and DC have been investigated widely and different studies demonstrated that reciprocal activations follow on from NK/DC interactions. The cross-talk between innate cells and DC which leads to innate lymphocyte activation and DC maturation was found to be multi-directional, involving not only cell-cell contacts but also soluble factors. The final outcome of these cellular interactions may have a dramatic impact on the quality and strength of the down-stream immune responses, mainly in the context of early responses to tumour cells and infectious agents. Interestingly, DC, NK and TCR-gammadelta cells also share similar functions, such as antigen uptake and presentation, as well as cytotoxic and tumoricidal activity. In addition, NK and NK T cells have the ability to kill DC. This review will focus upon the different aspects of the cross-talk between DC and innate lymphocytes and its key role in all the steps of the immune response. These cellular interactions may be particularly critical in situations where immune surveillance requires efficient early innate responses.

[Ileum intussusception in an adult: a case report]. / Invagination iléo-iléale chez un adulte.

Intussusception in adults is a rare cause of intestinal obstruction and is usually secondary to some lesion in the gastrointestinal tract. We report a case of intestinal obstruction due to ileo-ileal intussusception, an inflammatory fibroid polyp formed the leading edge of the intussusceptum, which is a rare polypoidal lesion of the gastrointestinal tract.

[Anatomo-clinical comparison: caecal duplication cyst]. / Confrontation anatomo-clinique: duplication caecale.

Enteric duplication cysts, and particularly caecal duplication cysts, are rare and generally benign congenital anomalies for which a diagnosis is difficult to make because they mimic other surgical diseases. A surgical management is the treatment of choice. The diagnosis can then be made or confirmed by histopathologic analysis.

Factors that influence cancer patients' anxiety following a medical consultation: impact of a communication skills training programme for physicians.

BACKGROUND: No study has yet assessed the impact of physicians' skills acquisition after a communication skills training programme on the evolution of patients' anxiety following a medical consultation. This study aimed to compare the impact, on patients' anxiety, of a basic communication skills training programme (BT) and the same programme consolidated by consolidation workshops (CW), and to investigate physicians' communication variables associated with patients' anxiety. PATIENTS AND METHODS: Physicians, after attending the BT, were randomly assigned to CW or to a waiting list. The control group was not a non-intervention group. Consultations with a cancer patient were recorded. Patients' anxiety was assessed with the State Trait Anxiety Inventory before and after a consultation. Communication skills were analysed according to the Cancer Research Campaign Workshop Evaluation Manual. RESULTS: No statistically significant change over time and between groups was observed. Mixed-effects modelling showed that a decrease in patients' anxiety was linked with screening questions (P = 0.045), physicians' satisfaction about support given (P = 0.004) and with patients' distress (P < 0.001). An increase in anxiety was linked with breaking bad news (P = 0.050) and with supportive skills (P = 0.013). No impact of the training programme was observed. CONCLUSIONS: This study shows the influence of some communication skills on the evolution of patients' anxiety. Physicians should be aware of these influences.

[Molecular characterization of Epstein-Barr virus associated with classical Hodgkin's lymphoma in Tunisia: prevalence of the LMP1 oncogene deletions and A and B viruses strains]. / Caractérisation moléculaire du virus d'Epstein-Barr associé au lymphome de Hodgkin classique en Tunisie: prévalence des délétions de l'oncogène LMP1 et des souches virales A et B.

Epstein-Barr virus (EBV) is detected in Hodgkin's lymphoma (HL) at variable frequencies, depending on various factors including the geographic location. The prevalence of EBV is high among HL diagnosed in the region of the center of Tunisia. The aim of the current work was to define the genotypic features of EBV in a series of EBV-positive HL in this area, in comparison to those of EBV found in association with benign lymphoadenopathies. A 30 bp and a 69 bp deletion within the LMP1 gene were detected in 41% and 11% of HL cases, respectively. In reactive lymph nodes, the 30 bp deletion was found in 43% of the cases. Type A EBV was detected in 84% of HL cases and in 96% of reactive lymphoadenopathies, and type B EBV was detected in others. No significant association was found between histological type of HL, age of the patients, or stage at diagnosis, and the molecular configuration of LMP1. However, LMP1 deletions were found more frequently among male patients. The significance of these results is discussed.

High levels of p105 (NFKB1) and p100 (NFKB2) proteins in HPV16-transformed keratinocytes: role of E6 and E7 oncoproteins.

We have previously shown that functional components of the NF-kappaB signaling pathway are up-regulated and sequestered in the cytoplasm of human papillomavirus 16 (HPV16)-transformed cell lines leading to a reduced activity of NF-kappaB. In this study, we examined the expression of the NF-kappaB precursors p100 and p105 in keratinocytes transformed or not by HPV16. Western immunoblotting experiments demonstrated high levels of p100 and p105 proteins not only in HPV16+ cervical carcinoma-derived keratinocytes but also in keratinocytes stably transfected by HPV16 E6 or E7 oncogenes. Moreover, p100 and p105 proteins were predominantly cytoplasmic and nuclear in keratinocytes expressing E7 and E6, respectively. A predominantly cytoplasmic localization of E7 protein was also detected in all keratinocytes expressing E7. Our results suggest that HPV16 E6 and E7 proteins modulate the expression and the subcellular localization of p100 and p105 NF-kappaB precursors.

[Alveolar echinococcosis]. / L'echinococcose alvéolaire: une zoonose d'apparition récente en Wallonie.

Alveolar echinococcosis is a serious parasitic disease, leading to large hepatic lesions. It must be distinguished from cystic echinococcosis, or hydatic cyst, caused by Echinococcus granulosus. Early diagnosis may allow surgical removal of the lesions by segmental hepatectomy, the only curative treatment. Parasitostatic medical treatment with albendazole may promote stabilization of the disease. Until recently, Belgium was considered a country at very low risk for alveolar echinococcosis, as no human case was reported, despite up to 51% of fox infection in southern Belgium autopsy series. Recently four patients presented with alveolar echinococcosis at the University Hospital Center of Liege, leading to the fear of a possible alveolar echinococcosis endemy in southern Belgium. Two of these patients underwent curative hepatectomy, but the other two had already pulmonary metastases at diagnosis and received palliative albendazole therapy. This article presents these cases, and reviews the clinical features of this parasitic disease.

[Anatomo-clinical confrontation: idiopathic pulmonary fibrosis]. / Confrontation anatomo-clinique. Dyspnée progressive chez un homme de 58 ans.

Idiopathic pulmonary fibrosis and pulmonary fibrosis associated with systemic diseases are the most frequent diffuse interstitial pulmonary diseases. They slowly but irrevocably progress towards terminal respiratory failure. They can also be complicated by severe acute respiratory failure and admission in the intensive care unit can be discussed. Despite invasive mechanical ventilation, anti-infectious and immunosuppressive treatments, the disease carries a high mortality rate. We report and discuss the case of a patient with idiopathic, pulmonary fibrosis (UIP) who underwent rapid clinical deterioration.

A new model for human intestinal preservation: comparison of University of Wisconsin and Celsior preservation solutions.

AIM: We compared University of Wisconsin (UW) and Celsior preservation solutions using a new model of human intestinal preservation that mimics the clinical conditions of small bowel procurement. METHODS: Intestinal grafts were harvested from four multiorgan donors. After classic warm dissection for organ procurement, an ileal segment of 50 cm was immediately flushed with Celsior. After the perfusion of the abdominal organs with UW, a second segment of adjacent ileum was harvested. The two intestinal grafts were then divided into segments by stapling, before immersion into the corresponding preservation solution (Celsior or UW) for 0-, 6-, 12-, or 24-hour incubation at 4 degrees C. A histological score was graded after blinded examination of three random specimens within each ileal graft for each duration of preservation. RESULTS: Control specimens showed normal histology. After 6 hours of preservation, most villi showed complete epithelial detachment although the crypts appeared intact. After 12 hours of preservation, a larger proportion of the villi showed extensive epithelial sloughing. After 24 hours, the damage involved the entire mucosa with the crypt epithelium largely detached from the basal membrane. No statistical difference in histological score was observed between the two preservation solutions. CONCLUSION: This study showed severe histological alterations of graft mucosa after short periods of preservation by UW or Celsior solutions. This model may be useful to evaluate improvements in the quality of preservation of human intestinal transplants.

Luminal contact with University of Wisconsin solution improves human small bowel preservation.

AIM: Under clinical conditions small bowel mucosa is stored without any contact between the mucosa and the preservation solution. We evaluated the impact of luminal contact with University of Wisconsin solution (UW) on the structural quality of small bowel preservation. METHODS: Segments of ileum harvested from stable multi-organ donors were flushed with UW. For each donor, ileal segments were placed in UW without any contact between the mucosa and the preservation solution (group A), as is practiced in clinical conditions. Adjacent segments were cut on their antimesenteric side and placed in UW so that their mucosa was widely in contact with the solution (group B). The grafts preserved in ice were removed from the preservation fluid at different times (0, 3, 6, or 12 hours). Tissues were studied by optical microscopy after H&E staining of formalin-fixed, paraffin-embedded specimens. A median histologic score was calculated after examination of three random slides for each ileal segment per time point. Comparisons were performed between tissues of groups A and B from the same donor. RESULTS: Control (0h) specimens showed normal histology. As early as 3 hours of preservation, group A tissues showed detachment of the villar epithelium. At 6 and 12 hours of preservation in this group further tissue alteration were obvious with complete epithelial detachment from the basal membrane of the villi. The histologic score of the segments preserved by luminal contact with UW was always significantly higher than the controls from the same donor. CONCLUSION: Luminal contact between the mucosa of intestinal grafts and UW improves the quality of human small bowel preservation.