[Inflammation during COVID-19]. / Inflammation au cours de la COVID-19.

Infection due to SARS-CoV-2 is associated with clinical features of diverse severity. Severe disease includes biological criteria of both inflammation and coagulation activation, and high circulating levels of pro- and anti-inflammatory cytokines. The most critical patients present with acute respiratory distress syndrome and multiple organ failure, resembling bacterial sepsis. Clinical trials have shown that steroids reduce mortality of severe cases, suggesting that inflammation as a mechanism of defense against viral invasion is excessive rather than insufficient. Several molecules targeting more specific pathways than steroids are under evaluation. Those reducing interleukin 6 activity have a certain degree of effectiveness. Anticoagulants and fibrinolytics have moderate impact on the hypercoagulation state. Like for bacterial sepsis, future trials will attempt therapy "individualization" based on biomarkers, but we still lack precision diagnostic tools.

: L'infection par le virus SARS-CoV-2 entraîne des tableaux de gravité variable. La biologie des formes graves comporte des critères d'inflammation et d'activation de la coagulation, ainsi que la circulation des cytokines pro- et anti-inflammatoires en grande quantité. Les formes les plus sévères comportent un syndrome de détresse respiratoire aiguë, voire une défaillance multiviscérale qui ressemble au sepsis d'origine bactérienne. Les essais thérapeutiques effectués dans ces formes graves indiquent que les corticoïdes en réduisent la mortalité, ce qui suggère que l'état hyper-inflammatoire peut être excessif plutôt qu'insuffisant dans notre défense contre l'infection virale. Plusieurs molécules plus sélectives que les corticoïdes sont à l'étude. Celles qui réduisent l'activité de l'interleukine 6 ont une certaine efficacité. L'état hyper-coagulable est peu influencé par les traitements anti-coagulants ou fibrinolytiques. Comme dans le sepsis bactérien, l'évolution se fera vers plus d'individualisation des traitements à partir de certains biomarqueurs, mais cette pratique se heurte encore à un manque de précision dans les outils diagnostiques.

[Inflammation and cancer : a complex two-way relationship]. / Inflammation et cancer : une relation complexe à double sens.

The relationships between inflammation and cancer are known since the original work by Virchow in the 19th century and have been largely confirmed after-wards. An interesting question is what might be the primum movens. Numerous clinical observations have shown that a chronic inflammatory state, as that observed with some infections, toxic agents or dysimmune diseases, may be associated with the development of cancer later on. Besides, cancer is generally accompanied by an inflammatory microenvironment, with numerous cellular and humoral components, which promotes both tumorigenesis and the invasivity of the tumour. This article aims at defining the pathophysiology of this association, with a description of underlying mechanisms and mediators, and at determining possible therapeutic implications.

: Les relations entre inflammation et cancer sont connues depuis les travaux pionniers de Virchow au 19ème siècle et ont été largement confirmées depuis lors. En fait, il s'agit d'une relation à double sens et la question est de savoir quel est le primum movens. De nombreuses observations cliniques ont montré qu'un état inflammatoire chronique, tel qu'on peut l'observer avec certaines infections, certains toxiques ou encore des maladies dysimmunitaires, peut être associé, à terme, au développement d'un cancer. Par ailleurs, le cancer s'accompagne généralement d'un microenvironnement inflammatoire, avec de nombreuses composantes cellulaires et humorales, qui favorise la tumorigenèse et l'invasivité de la tumeur. Cet article a pour objectif de définir la physiopathologie de cette association, en décrivant les mécanismes et médiateurs sous-jacents, et d'en déterminer les éventuelles implications thérapeutiques.

WITHDRAWN: A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

The article has been withdrawn at the request of the authors and editor because of incorrect authorship, which is considered a form of unethical publication. The Publisher apologizes for any inconvenience this may cause.

A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

BACKGROUND AND STUDY AIMS: The current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC) is surgery-first followed by adjuvant chemotherapy. We review our single center experience in a PDAC cohort managed by the surgery-first strategy. We then compare our data to those of Belgian and international literature. PATIENTS METHODS: We reviewed a series of 83 consecutive resectable patients with PDAC, treated by the surgery-first approach in a Belgian Academic Hospital between 2007 and 2013. The outcomes were assessed with univariate and multivariate Cox regression analysis. Kaplan-Meier curves were drawn according to patient groups. RESULTS: For the entire population, the median survival (MS) was 18.4 months; the 1-year relapse-free survival was 56%, and the 5-year overall survival (OS) was 13%. The size of the primary tumor larger than 3 cm (OS, HR = 1.76, p = 0.033) and vascular resection (DFS, HR = 2.1, p = 0.024) were the single independent prognostic factors in the multivariate analysis of this cohort. Only 69% of the patients received adjuvant chemotherapy, and more than 75% of them demonstrated no chance of survival beyond 3 years because they harbored poor prognostic factors, recognized only postoperatively. CONCLUSIONS: Our results and those published in the literature brought to light the limited perspectives of the surgery-first strategy in a population of apparently resectable pancreatic cancers. In comparison, data from reported neo-adjuvant series deserve our interest to bring this strategy upfront in selected patients in the context of close observational monitoring and randomized trials. The actual standard of care for resectable PDAC is surgery-first followed by adjuvant chemotherapy. The performance of this strategy relies on the dedicated imaging that does not accurately recognize the limits of the tumor and the high prevalence of adverse prognostic factors. Moreover, pancreatectomy remains associated with high postoperative complication rates and the poor completion of adjuvant therapy. This translates into poor long-term survival figures. In our series the MS was 18.4 months and 5-year OS was 13%. The disease-free survival (DFS) was 15.6 months, 1 and 3-year DFS were 56 and 26%, respectively. The variables that significantly correlated with OS in univariate analysis are tumor size and lymph node involvement. Regarding DFS, vascular resection was the only significant factor. In the multivariate analysis, the only significant factor related to OS remained the tumor size >3 cm in greatest diameter. Vascular resection remained significant for DFS. 31% of the patients did not receive any chemotherapy at all before the 6-month period following resection. The rates of complete resections compared favorably with those of a surgery-first strategy with no excess of operative mortality, complications and early relapse rates. The advantages of a chemotherapy-first approach, eventually combined with chemo-radiotherapy, are to offer higher combined therapy completion rates and improve the level of free resection margins, lymph node involvement and patient selection. The advent of safe, more potent chemotherapy combinations has the potential to further improve survival when administered upfront.

[Malignant phyllodes tumour : a case report]. / Le cas clinique du mois Tumeur phyllode maligne : à propos d'un cas avec composante hétérologue.

A 28 year old woman has suffered over the previous month from a post-traumatic swelling sensation of the left breast. Ultrasonography demonstrates a 9 cm, sharply-cut, rounded, hypo-echogenic lesion. Surgery is performed, with the hypothesis of an haematoma. The pathological analysis of the lesion shows a malignant phyllodes tumour with heterologous rhabdomyosarcomatous features. No metastasis is found. A radical mastectomy is performed and the patient benefits from an adjuvant radio-chemotherapy. Phyllodes tumours represent up to 1 % of all mammary cancers, with 10-20 % of malignant lesions. These tumours behave differently from usual breast cancers. This atypical case, arising in a traumatic context, provides the opportunity to discuss the treatment and classification of phyllodes tumours of the breast.

Nous rapportons le cas d'une patiente de 28 ans se plaignant d'une sensation de tension mammaire, évoluant depuis un mois et apparue dans le décours d'un traumatisme. L'échographie démontre une lésion arrondie, hypo-échogène, de 9 cm aux contours nets. Après chirurgie réalisée dans l'hypothèse d'un hématome, l'analyse anatomo-pathologique révèle une tumeur phyllode maligne avec composante hétérologue de type rhabdomyosarcome. Le bilan d'extension ne met en évidence aucune métastase. La patiente a bénéficié d'une mastectomie radicale ainsi que d'une radio-chimiothérapie adjuvante. Les tumeurs phyllodes, qui représentent jusqu'à 1 % des tumeurs mammaires, dont 10-20 % sont de nature maligne, constituent une entité rare avec un comportement différent des autres tumeurs malignes mammaires. Ce cas, dont la présentation est atypique, permet de discuter de la classification et du traitement des tumeurs phyllodes du sein.

[CONTROVERSIES REGARDING THE ACCURACY AND LIMITATIONS OF FROZEN SECTION IN THYROID PATHOLOGY: AN EVIDENCE-BASED ASSESSMENT]. / INTÉRÊTS ET LIMITES DE L'EXAMEN EXTEMPORANÉ EN PATHOLOGIE THYROÏDIENNE. Revue systématique de la littérature et évaluation fondée sur les preuves.

Palpable thyroid nodules are present clinically in 4-7% of the population and their prevalence increases to 50%-67% when using high-resolution neck ultrasonography. By contrast, thyroid carcinoma (TC) represents only 5-20% of these nodules, which underlines the need for an appropriate approach to avoid unnecessary surgery. Frozen section (PS) has been used for more than 40 years in thyroid surgery to establish the diagnosis of malignancy. However, a controversy persists regarding the accuracy of FS and its place in thyroid pathology has changed with the emergence of fine-needle aspiration (FNA). A PubMed Medline and SpringerLink search was made covering the period from January 2000 to June 2012 to assess the accuracy of ES, its limitations and indications for the diagnosis of thyroid nodules. Twenty publications encompassing 8.567 subjects were included in our study. The average value of TC among thyroid nodules in analyzed studies was 15.5 %. ES ability to detect cancer expressed by its sensitivity (Ss) was 67.5 %. More than two thirds of the authors considered PS useful exclusively in the presence of doubtful ENA and for guiding the surgical extension in cases confirmed as malignant by FNA; however, only 33% accepted FS as a routine examination for the management of thyroid nodules. The influence of FS on surgical reintervention rate in nodular thyroid pathology was considered to be negligible by most studies, whereas 31 % of the authors thought that FS has a favorable benefit by decreasing the number of surgical re-interventions. In conclusion, the role of FS in thyroid pathology evolved from a mandatory component for thyroid surgery to an optional examination after a pre-operative FNA cytology. The accuracy of FS seems to provide no sufficient additional benefit and most experts support its use only in the presence of equivocal or suspicious cytological features, for guiding the surgical extension in cases confirmed as malignant by FNA and for the identification of other potentially confusing intraoperative findings.

Belgian consensus guidelines for follow-up of women with cervical cytological abnormalities.

In medical care cervical cancer screening is important because it enables the detection of precancer and cancer at an early stage. By adequate treatment after a screening-detected lesion it helps to reduce the mortality related to cervical cancer. Worldwide, many millions of women have smears taken at a more or less regular base and of these, approximately 7% are abnormal, and follow-up is thus required.As this represents an important cost in medical health care and has serious consequences for the affected women, it is important to have uniform and clear guidelines to allow an optimal follow-up and clinical management. A system for the uniform reporting of cervical cytology has been designed by the National Cancer Institute (U.S.A.) and resulted in the Bethesda System 1991. The present paper and the terminology used are based on the Bethesda System revised in 2001. It explains the guidelines, based on the 2001 Bethesda System and the 2004 consensus guidelines for the management of women with cervical cytological abnormalities, as developed by the members of the Board of the Belgian Society of Clinical Cytology, and adapted to the Belgian situation.

[Vaccination perspective against human papillomavirus and consequences for the screening of uterine cervical neoplasm]. / Perspectives de vaccination contre les papillomavirus humains et conséquences pour le dépistage du cancer du col utérin.

The link between cervical cancer and some types of human papillomavirus (HPV) has generated, in recent years, a great interest for the development of anti-HPV vaccines. The purpose of this article is to review the current perspectives for anti-HPV prophylactic vaccination and to describe the potential implications for the cervical cytology screening programs.

A patient who survived total colonic ulcerative colitis surinfected by cytomegalovirus complicated by toxic megacolon and disseminated intravascular coagulation.

The authors report the case of a patient aged 60-year-old who survived ulcerative colitis complicated by toxic megacolon and disseminated intravascular coagulation. This patient was not known for this ulcerative colitis and was first hospitalised for a suspicion of diverticulitis. The admission symptoms were fever, abdominal pain and bloody diarrhoea. The evolution was defavorable under antibiotics and sulfasalazine. The patient was readmitted 5 days after he left hospital, and the diagnosis of UC was based on colon biopsy made during the first hospitalisation. A treatment with methylprednisolone was started and the patient worsened day by day with apparition of toxic megacolon and disseminated intravascular coagulation. Subtotal colectomy was performed for degradation of general status and coagulation factors. Pathological findings confirmed ulcerative colitis with toxic megacolon. Cytomegalovirus inclusions were demonstrated on the colonic specimen and confirmed by PCR. In this report the authors discuss the etiology of toxic megacolon and disseminated intravascular coagulation in ulcerative colitis surinfected by cytomegalovirus. Mortality of these pathologies is high necessitating rapid diagnosis of cytomegalovirus infection by sigmoid biopsy. Management requires immunosupression interruption and ganciclovir therapy, or surgery in unsuccessful medical treatment.

[Immunologic response to (pre)neoplastic cervical lesions associated with human papillomavirus]. / Rôle des réponses immunitaires dans les lésions (pré) néoplasiques cervicales associées aux papillomavirus humains.

Etiopathogenic and epidemiological studies have demonstrated that viruses are etiologically linked to approximately 20% of all human malignancies worldwide. Human papillomavirus (HPV) is one of the best characterized viruses associated with human cancer diseases, especially in the uterine cervix. Although the role of HPV is well established in the cellular transformation and maintenance of the malignant phenotype of keratinocytes, the viral infection by itself is not sufficient for cancer development. The small number of infected individuals eventually developing cancer of the cervix and the long latency period between primary infections and cancer emergence suggest that additional environmental or host factors are involved in malignant progression. In this context, the local mucosal immunity might be expected to play a key role in the host defence against HPV infection and associated-(pre)cancerous lesions. The purpose of this work was to analyse the immune co-factors implicated in the initiation and promotion of the neoplastic process. We have shown that the transformation zone (TZ), where a substantial majority of cervical (pre)cancers develop, is characterized by intrinsic immune alterations which could explain why this region is at higher risk of developing cancer. We have also provided evidence that the viral infection of cervical keratinocytes contributes to the local immunodeficiency by inhibiting the production of soluble and membrane molecules important for the migration and function of antigen-presenting cells.