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Omics technologies has opened new possibilities to assess environmental risks and to understand the mode(s) of action of pollutants. Coupled to dose-response experimental designs, they allow a non-targeted assessment of organism responses at the molecular level along an exposure gradient. However, describing the dose-response relationships on such high-throughput data is no easy task. In a first part, we review the software available for this purpose, and their main features. We set out arguments on some statistical and modeling choices we have made while developing the R package DRomics and its positioning compared to others tools. The DRomics main analysis workflow is made available through a web interface, namely a shiny app named DRomics-shiny. Next, we present the new functionalities recently implemented. DRomics has been augmented especially to be able to handle varied omics data considering the nature of the measured signal (e.g. counts of reads in RNAseq) and the way data were collected (e.g. batch effect, situation with no experimental replicates). Another important upgrade is the development of tools to ease the biological interpretation of results. Various functions are proposed to visualize, summarize and compare the responses, for different biological groups (defined from biological annotation), optionally at different experimental levels (e.g. measurements at several omics level or in different experimental conditions). A new shiny app named DRomicsInterpreter-shiny is dedicated to the biological interpretation of results. The institutional web page https://lbbe.univ-lyon1.fr/fr/dromics gathers links to all resources related to DRomics, including the two shiny applications.

Background Inflammatory bowel disease [IBD] is associated with an increased risk of developing lymphoma. Although recent data have clarified the epidemiology of lymphoma in IBD patients, the clinical and pathological characteristics of lymphoma in IBD remain poorly known. Methods Patients with IBD and lymphoma were retrospectively identified in the framework of a national collaborative study including the Groupe d'Étude Thérapeutique des Affections Inflammatoires du Tube Digestif [GETAID] and the Lymphoma Study Association [LYSA]. We characterized clinical and prognostic features for the three most frequent lymphoma subtypes occurring in IBD. We performed a multicentre case-control study. Controls [lymphoma de novo ] were matched [5:1] to cases on gender, age at diagnosis, lymphoma subtype, year of diagnosis, and IPI/FLIPI indexes. Overall survival and progression-free survival were compared between cases and controls. Results In total, 133 IBD patients with lymphoma were included [males = 62.4%, median age at lymphoma diagnosis = 49 years in males; 42 years in females]. Most had Crohn's disease [73.7%] and were exposed to thiopurines [59.4%]. The most frequent lymphoma subtypes were diffuse large B cell lymphoma [DLBCL, 45.1%], Hodgkin lymphoma [HL, 18.8%], and follicular lymphoma [FL, 10.5%]. When matched with 365 controls, prognosis was improved in IBD patients with DLBCL compared to controls [ p  = 0.0064, hazard ratio = 0.36] or similar [HL and FL]. Conclusions Lymphomas occurring in IBD patients do not seem to have a worse outcome than in patients without IBD. Due to the rarity of this situation, such patients should be managed in expert centres. [ABSTRACT FROM AUTHOR]

Objective When transsphenoidal surgery (TSS) does not cure Cushing's disease (CD), 4 treatments are available: drug treatment (DT), second TSS (2nd TSS), bilateral adrenalectomy (BA), and pituitary radiotherapy (PR). DT is attractive but supposes long-term continuation, which we aimed to evaluate. Design and Methods Retrospective study, in a center prioritizing 2nd TSS, of 36 patients, including 19 with TSS failure and 17 with recurrence, out of 119 patients with CD treated by a first TSS, average follow-up 6.1 years (95% confidence interval 5.27-6.91). Control was defined as normalization of urinary free cortisol (UFC) and final treatment (FT) as the treatment allowing control at last follow-up. We also analyzed discontinuation rates of DT in published CD prospective clinical trials. Results Control was achieved in 33/36 patients (92%). DT was initiated in 29/36 patients (81%), allowing at least 1 normal UFC in 23/29 patients (79%) but was discontinued before last follow-up in 18/29 patients (62%). DT was FT in 11/29 patients (38%), all treated with cortisol synthesis inhibitors. Second TSS was FT in 8/16 (50%), BA in 14/14 (100%), and PR in 0/5. In published trials, discontinuation of DT was 11% to 51% at 1 year and 32% to 74% before 5 years. Conclusion DT allowed at least 1 normal UFC in 23/29 patients (79%) but obtained long-term control in only 11/29 (38%), as discontinuation rate was high, although similar to published data. Interestingly, a successful 2nd TSS was the cause for discontinuing efficient and well-tolerated DT in 5 patients. Further studies will show whether different strategies with cortisol synthesis inhibitors may allow for a lower discontinuation rate in patients not candidates for a 2nd TSS so that BA may be avoided in these patients. [ABSTRACT FROM AUTHOR]

Worldwide, gastric adenocarcinoma is a major public health problem, accounting for 6% of all cancers. In France, the incidence of gastric adenocarcinoma has been stabilized at around 4,700 new cases/year, thanks to better control of risk factors, in particular the eradication of Helicobacter pylori. Around 3% of all cases are hereditary forms of the disease, which are part of cancer predisposition syndromes resulting from the presence of constitutional pathogenic variants in some tumor suppressor genes. The best-known predisposition syndromes that increase the risk of developing gastric adenocarcinoma are hereditary diffuse gastric cancer syndrome (CDH1 and CTNNA1 genes; estimated lifetime risk of around 40%), Lynch syndrome (germline alteration of one of the genes in the Mismatch Repair (MMR) system for repairing DNA mismatches (MLH1, PMS2, MSH2, MSH6); estimated lifetime risk of around 10 %) or certain digestive polyposis (Peutz-Jeghers syndrome linked to STK11, juvenile polyposis linked to SMAD4, GAPPS syndrome linked to APC). Identifying these patients is essential in order to implement preventive strategies and screening for gastric adenocarcinoma in unaffected relatives, as well as to be able to guide treatment strategies in patients with gastric adenocarcinoma (prognostic impact, treatment and risk of second cancer). Screening strategies for gastric adenocarcinoma in these patients include upper gastrointestinal endoscopy, and sometimes lead to discussion of prophylactic surgery, warranting management in an expert centre with a multidisciplinary referral committee. Although these syndromes are rare, the role of oncogenetics in the management of patients at high risk of developing gastric adenocarcinoma (or suffering from this cancer) is crucial, and new predisposition genes are regularly described which may also have therapeutic implications. [ABSTRACT FROM AUTHOR]

In France, biliary tract cancers (BTCs) account for 15% of all primary liver cancers, and are the second most common primary liver cancer after hepatocellular carcinoma. Although rare, their incidence is increasing and their prognosis remains poor, with an overall survival rate (OS) estimated at less than 20% at five years, all stages combined. Only 20-30% of patients with BTC are eligible for potentially curative surgery at diagnosis, of whom 50-70% will have a recurrence. Because of this high risk of recurrence, adjuvant treatment is recommended. Since 2018, several phase III trials have clarified the adjuvant strategy for BTC. Gemcitabine ± platinum-based chemotherapy, used in advanced stages, did not significantly improve OS in the adjuvant setting. The BILCAP trial, although negative on its primary objective, reported a benefit in terms of OS and disease-free survival, making capecitabine for 6 months in adjuvant setting the standard of care for resected cholangiocarcinoma and gallbladder adenocarcinoma. A comparison between capecitabine and gemcitabine + platinum chemotherapy is still being studied in a large-scale phase III trial (ACTICCA-1 [NCT02170090]), which results are expected in 2025. Adjuvant radiotherapy or radio-chemotherapy have only been assessed in single-arm phase II trials and have never been prospectively compared with chemotherapy alone: they are therefore not currently recommended. Immunotherapy and molecular targeting strategies developed in recent years for advanced cholangiocarcinoma and gallbladder adenocarcinoma (especially FGFR2 rearrangements, IDH1 mutations, microsatellite instability, HER2 overexpression) have not been evaluated in the adjuvant setting. Encouraging the inclusion of these patients in clinical research protocols will help to better define their place in personalized adjuvant strategies in the future. [ABSTRACT FROM AUTHOR]