[Endometrial cancer in the crossroads of modernity and immunotherapy]. / Cancer de l'endomètre : entre modernité et immunothérapie.

Frequent and with an increasing incidence in some territories, endometrial cancer is a complex disease leading to significant morbidity among affected patients. After years of research and the implementation of state-of-the-art molecular and gene assays significant breakthroughs were made. Through a better understanding of the underlying mechanisms of uterine carcinogenesis, a more precise and personalized risk stratification and the incorporation of immunotherapy, the treatment of endometrial cancer is experiencing significant improvements. This evolution, caries the genuine hope for an accurate selection of patients based on specific cancer-related characteristics, to tailor both treatment intensity and selection.

Le cancer du corps de l'utérus est une maladie fréquente, complexe et source de morbidité importante. L'implémentation de moyens de recherche de pointe, notamment l'immunothérapie, le séquençage génétique et les études moléculaires, ont abouti aux avancées discutées dans cet article. À travers une meilleure compréhension des mécanismes de la carcinogenèse endométriale, une stratification plus précise et personnalisée du risque de récidive et l'essor de l'immunothérapie, le traitement du cancer de l'utérus connaît actuellement un incontestable renouveau. Cette révolution, porteuse d'espoir, promet l'adéquation la plus exacte possible entre les traitements et l'agressivité de la maladie.

Type 2 Diabetes and Cancer: An Umbrella Review of Observational and Mendelian Randomization Studies.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of developing several common cancers, but it is unclear whether this association is causal. We aimed to summarize the evidence on T2DM and cancer and evaluate the validity of associations from both observational and Mendelian randomization (MR) studies. METHODS: We performed an umbrella review of the evidence across meta-analyses of observational studies that examined associations of T2DM with risk of developing or dying from site-specific cancers, and MR studies that explored the potential causal association of T2DM and associated biomarkers with cancer risk. RESULTS: We identified eligible observational meta-analyses that assessed associations between T2DM and cancer incidence for 18 cancer sites, cancer mortality for seven sites, and cancer incidence or mortality for four sites. Positive associations between T2DM and six cancers reached strong or highly suggestive evidence. We found eight MR studies assessing the association of genetically predicted T2DM and seven and eight studies assessing the association of genetically predicted fasting insulin or fasting glucose concentrations, respectively, upon site-specific cancers. Positive associations were found between genetically predicted T2DM and fasting insulin and risk of six cancers. There was no association between genetically predicted fasting plasma glucose and cancer except for squamous cell lung carcinoma. CONCLUSIONS: We found robust observational evidence for the association between T2DM and colorectal, hepatocellular, gallbladder, breast, endometrial, and pancreatic cancers. IMPACT: Potential causal associations were identified for genetically predicted T2DM and fasting insulin concentrations and risk of endometrial, pancreas, kidney, breast, lung, and cervical cancers.

[Small-cell lung cancer: management and novelties]. / Cancer du poumon à petites cellules†: prise en charge et nouveautés.

Small cell lung cancer is a recalcitrant malignancy with 5-year survival rates of less than 20%. In the majority of cases, patients have metastatic disease at diagnosis despite the new screening method by low-dose CT-scan. The high throughput sequencing has deepened our understanding of its biology. While the treatment of localized disease has changed little, the arrival of immune checkpoint inhibitors have revolutionized the management of extensive disease. At the same time, new strategies involving certain potential genetic targets are being analyzed on a large scale that could become valuable therapeutic alternatives in the future. Radiation therapy remains a very useful therapeutic modality in all stages of the disease. This article aims to review the epidemiology, molecular pathology, management and innovative therapies in small-cell lung cancer.

Le cancer pulmonaire à petites cellules (CPPC) est une tumeur récalcitrante avec une survie à 5 ans de moins de 20 %. Il est fréquemment découvert à un stade métastatique malgré le nouveau dépistage par computed tomography scan low-dose. Le séquençage à haut débit a permis d'approfondir notre compréhension de sa biologie. Bien que le traitement du CPPC localisé ait peu évolué, l'immunothérapie par inhibiteurs des points de contrôle a révolutionné la prise en charge de la maladie métastatique. Parallèlement, de nouvelles stratégies impliquant certaines cibles génétiques potentielles sont en cours d'évaluation et pourraient se révéler précieuses à l'avenir. La radiothérapie reste très utile à tous les stades de la maladie. Cet article passe en revue l'épidémiologie, la pathologie moléculaire, la prise en charge et les thérapies novatrices dans le CPPC.

Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition.

Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.

[Oncology, what's new in 2018]. / Oncologie.

The year 2018 has been incredibly prolific regarding novelties. Several studies have given impressive results and offer new anticancer perspectives. Immunotherapy is gaining more and more place defining a new standard of care for different types of cancer. In parallel with a new approach combining immunotherapy and chemotherapy that is emerging, new forms of adoptive immunotherapy are on the path of approval by regulatory authorities. At the decision-making level, a large somatic genetic analysis is becoming dominant, whereas the addition of more specific biomarkers is still needed regarding immunotherapy. This article aims to summarize the significant new developments in oncology for 2018 concerning the five most common cancers and adoptive cellular immunotherapy.

L'année 2018 a été extrêmement prolifique en termes de nouveautés. Plusieurs études ont amené des résultats intéressants et offrent de nouvelles perspectives anticancéreuses. L'immunothérapie prend de plus en plus de place définissant un nouveau standard pour le traitement des différents types de cancer. En parallèle d'une nouvelle approche combinant l'immunothérapie et la chimiothérapie qui voit le jour, des nouvelles formes d'immunothérapie adoptive se situent sur la voie d'approbation par les autorités réglementaires. Sur le plan décisionnel, l'analyse génétique somatique large des tumeurs devient prépondérante, alors que l'addition de biomarqueurs plus spécifiques est encore nécessaire concernant l'immunothérapie. Cet article a pour but de résumer les nouveautés majeures survenues en oncologie pour 2018 concernant les cinq cancers les plus fréquents et l'immunothérapie cellulaire adoptive.

Ribavirin for treating Crimean Congo haemorrhagic fever.

BACKGROUND: Crimean Congo haemorrhagic fever (CCHF) is a tick-borne disease that occurs in parts of Asia, Europe and Africa. Since 2000 the infection has caused epidemics in Turkey, Iran, Russia, Uganda and Pakistan. Good-quality general supportive medical care helps reduce mortality. There is uncertainty and controversy about treating CCHF with the antiviral drug ribavirin. OBJECTIVES: To assess the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (OVID); Science Citation Index-Expanded, Social Sciences Citation index, conference proceedings (Web of Science); and CINAHL (EBSCOHost). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for trials in progress. We conducted all searches up to 16 October 2017. We also contacted experts in the field and obtained further studies from these sources. SELECTION CRITERIA: We evaluated studies assessing the use of ribavirin in people with suspected or confirmed Crimean Congo haemorrhagic fever. We included randomised control trials (RCTs); non-randomised studies (NRSs) that included more than 10 participants designed as cohort studies with comparators; and case-control studies. DATA COLLECTION AND ANALYSIS: Two review authors assessed eligibility, risk of bias, and extracted data. For non-randomized studies we used the ROBINS-I tool to assess risk of bias. The main effects analysis included all studies where we judged the risk of bias to be low, moderate or high. We summarized dichotomous outcomes using risk ratios (RRs) and continuous outcomes using mean differences (MDs), and used meta-analyses where appropriate. We carried out a subsidiary appraisal and analysis of studies with critical risk of bias for the primary outcome, as these are often cited to support using ribavirin. MAIN RESULTS: For the main effects analysis, five studies met our inclusion criteria: one RCT with 136 participants and four non-randomized studies with 612 participants. We excluded 18 non-randomized studies with critical risk of bias, where none had attempted to control for confounding.We do not know if ribavirin reduces mortality (1 RCT; RR 1.13, 95% confidence interval (CI) 0.29 to 4.32; 136 participants; very low-certainty evidence; 3 non-randomized studies; RR 0.72, 95% CI 0.41 to 1.28; 549 participants; very low-certainty evidence). We do not know if ribavirin reduces the length of stay in hospital (1 RCT: mean difference (MD) 0.70 days, 95% CI -0.39 to 1.79; 136 participants; and 1 non-randomized study: MD -0.80, 95% CI -2.70 to 1.10; 50 participants; very low-certainty evidence). We do not know if it reduces the risk of patients needing platelet transfusions (1 RCT: RR 1.23, 95% CI 0.77 to 1.96; 136 participants; very low-certainty evidence). For adverse effects (including haemolytic anaemia and a need to discontinue treatment), we do not know whether there is an increased risk with ribavirin in people with CCHF as data are insufficient.We do not know if adding ribavirin to early supportive care improves outcomes. One non-randomized study assessed mortality in people receiving ribavirin and supportive care within four days or less from symptom onset compared to after four days since symptom onset: mortality was lower in the group receiving early supportive care and ribavirin, but it is not possible to distinguish between the effects of ribavirin and early supportive medical care alone.In the subsidiary analysis, 18 studies compared people receiving ribavirin with those not receiving ribavirin. All had a critical risk of bias due to confounding, reflected in the mortality point estimates favouring ribavirin. AUTHORS' CONCLUSIONS: We do not know if ribavirin is effective for treating Crimean Congo haemorrhagic fever. Non-randomized studies are often cited as evidence of an effect, but the risk of bias in these studies is high.

Allergen immunotherapy for allergic asthma: a systematic overview of systematic reviews.

BACKGROUND: There is clinical uncertainty about the effectiveness and safety of allergen immunotherapy (AIT) for the treatment of allergic asthma. OBJECTIVES: To undertake a systematic overview of the effectiveness, cost-effectiveness and safety of AIT for the treatment of allergic asthma. METHODS: We searched nine electronic databases from inception to October 31, 2015. Systematic reviews were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme quality assessment tool for systematic reviews. Data were descriptively and thematically synthesized. RESULTS: We identified nine eligible systematic reviews; these focused on delivery of AIT through the following routes: subcutaneous (SCIT; n = 3); sublingual (SLIT; n = 4); and both SCIT and SLIT (n = 2). This evidence found that AIT delivered by SCIT and SLIT can improve medication and symptom scores and measures of bronchial hyper-reactivity. The impact on measures of lung function or asthma control was however less clear. We found no systematic review level evidence on the cost-effectiveness of SCIT or SLIT. SLIT had a favorable safety profile when compared to SCIT, particularly in relation to the risk of systemic reactions. CONCLUSIONS: AIT has the potential to achieve reductions in symptom and medication scores, but there is no clear or consistent evidence that measures of lung function can be improved. Bearing in mind the limitations of synthesizing evidence from systematic reviews and the fact that these reviews include mainly dated studies, a systematic review of current primary studies is now needed to update this evidence base, estimate the effectiveness of AIT on asthma outcomes and to investigate the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT.

Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.

OBJECTIVES:  To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. DESIGN:  Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. STUDY ELIGIBILITY CRITERIA:  Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. DATA SOURCES:  Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. RESULTS:  Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. CONCLUSIONS:  Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences.

Biomarkers of Inflammation and Immune Function and Risk of Colorectal Cancer.

A substantial number of prospective epidemiological studies have been conducted to investigate the association between biomarkers of inflammation and immune function and risk of colorectal cancer. Although pre-diagnostic concentrations of these biomarkers, especially C-reactive protein, have been associated with a higher risk of colorectal cancer in some studies, this association does not seem to have a robust support without hints of bias. Future prospective studies should evaluate multiple inflammatory biomarkers with longitudinal measures over the follow-up taking advantage of new multiplex cytokine quantification arrays and use more sophisticated joint or biomarker pattern statistical approaches to capture the complex and dynamic interplay between biomarkers and risk of colorectal cancer. Large collaborative consortia and Mendelian randomization studies should be encouraged to diminish the threat of biases and improve the reliability of this literature.

Interleukin-6 and risk of colorectal cancer: results from the CLUE II cohort and a meta-analysis of prospective studies.

PURPOSE: The association between prediagnostic interleukin-6 (IL-6) concentrations and risk of colorectal cancer was evaluated in a nested case-control study and a meta-analysis of prospective studies. METHODS: Colorectal cancer cases (n = 173) and matched controls (n = 345) were identified between 1989 and 2000 among participants in the CLUE II cohort of Washington Country, Maryland. Matched odds ratios and the corresponding 95 % confidence intervals (CIs) were estimated using conditional logistic regression models. RESULTS: Participants in the highest third of plasma IL-6 concentration had a 2.48 times higher risk of colon cancer compared to participants in the bottom third (95 % CI 1.26-4.87; p-trend 0.02) after multivariate adjustment. This association did not differ according to the stage of disease, age, sex, or other potential modifying variables and remained statistically significant after adjustment for C-reactive protein concentrations. No statistically significant association was observed for rectal cancer risk. The meta-analysis of six prospective studies yielded an increased but borderline statistically significant risk of colon cancer per 1 U increase in naturally logarithm-transformed IL-6 (summary RR 1.22; 95 % CI 1.00-1.49; I (2) 46 %). An inverse association was noted for rectal cancer (RR 0.69; 95 % CI 0.54-0.88; I (2) 0 %), but there was evidence for small-study effects (p 0.02). CONCLUSION: Our findings provide support for a modest positive association between IL-6 concentrations and colon cancer risk. More work is needed to determine whether IL-6 is a valid marker of colorectal inflammation and whether such inflammation contributes to colon and rectal cancer risk.

Thirteen years follow-up of heart myxoma operated patients: what is the appropriate surgical technique?

BACKGROUND: Cardiac myxoma is a benign neoplasm that represents the most prevalent primary tumor of the heart. If not treated with the right surgical technique recurrence occurs. Aim of our study is to present our surgical approach and the histology of the tumors resected. METHODS: All patients, except for one, underwent extracorporeal circulation and mild hypothermia, right atrial or both atrial incision and excision of the fossa ovalis, followed by prosthetic patch suturing. All specimens were submitted for microscopic evaluation (haematoxylin-eosin). We contacted personally each patient and asked them to complete a standardized questionnaire, concerning their peri-operative characteristics. RESULTS: Six cases were "active" myxomas, 3 were "mildly active" and 3 were "inactive". "Normal differentiation" was seen in 6, "medium" in 1 and "poor" in 5 cases. In our series there were no recurrences recorded during the follow-up period. CONCLUSIONS: The ideal approach, according to our experience is right atrial or both atrial incision as described by Shumacker and King, with excision of the fossa ovalis and the surrounding tissues and closure with a pericardial patch. Such a technique provides an excellent long-term survival in these patients.