Oncogenesis Stress Signaling

International audience

ABSTRACTBackgroundManagement of cutaneous metastases in colorectal cancer is crucial because it can significantly impact patient survival.ObjectiveTo assess the global prognosis of skin metastases among patients treated for colorectal cancer.MethodsA systematic review of the PubMed database only was conducted for English articles or reports published between 1 January 1990 and 1 November 2023. Reports concerning clinical outcomes of patients with cutaneous metastases of colorectal cancer and systematic reviews of the literature were included. Study characteristics and results of eligible studies were independently extracted by two reviewers (A.C.E., E.T.). The histology, locations, and prognosis of patients with skin metastases of colorectal cancer were analyzed.ResultsData were obtained from almost 100 articles, most of which were case reports. Follow‐up data were available for 62 patients. The most common site was rectal adenocarcinoma (58%), followed by right and left colon adenocarcinomas. A significant number of these metastases were metachronous (61%). The median time to death was 5.5 months [interquartile range, 3–10], ranging from 1 to 60 months. Treatment of cutaneous metastases, even if associated with other metastases, significantly improved overall survival (p < 0.001; hazard ratio, 0.15), regardless of the proposed treatment.ConclusionsWe carried out the most extensive review of the literature concerning cutaneous metastases of colorectal cancer to date. The review showed that cutaneous metastases are associated with a poor prognosis and short survival time. We suggest treating patients with cutaneous metastasis as if such metastasis were a surrogate marker or sentinel for aggressive metastatic disease.

Little is known about the therapeutic trajectory of patients treated in hospitals for intrahepatic cholangiocarcinoma (iCCA) and patterns of care in daily clinical practice. An observational retrospective study was conducted on the French National Hospital Discharge Database. All patients with a new diagnosis of iCCA who had a first hospital stay (S1) from January 2016 to December 2021 were included. They were followed up until December 2021, or in-hospital death, whichever occurred first. Crude annual hospitalization rates were computed. Treatment lines were identified with an artificial intelligence algorithm [Analysis of Treatment Lines using Alignment of Sequences (ATLAS)]. A multistate model was used to compute the transition rates between lines. Overall, 13 491 patients were included and the mean (standard deviation) follow-up duration was 13.1 months (17.9 months). The median age at S1 was 72.0 years and 55.9% were male. Nearly 20.7% were admitted via emergency services for S1, and 32.1% had metastases. Between 2016 and 2021, the crude annual rate of new iCCA cases increased from 3.08 [95% confidence interval (CI) 2.94-3.24] in 2016 (n = 1598) to 4.12 (95% CI 3.95-4.29) per 100 000 adult person-years in 2021 (n = 2188). Among 4855 patients receiving first-line systemic therapy (L1), 37.7% (95% CI 36.0% to 39.3%) received a second-line 2 (L2) during the follow-up. The median time between the start of L1 and the beginning of L2 was 7.0 months. This study provides up-to-date national real-world data on iCCA, revealing an increasing burden year by year in France, a poor outcome of patients with iCCA on L1 systemic therapy, and the low proportion of patients receiving an L2.

Erythropoiesis, a remarkably dynamic and efficient process responsible for generating the daily quota of red blood cells (approximately 280 &plusmn; 20 billion cells per day), is crucial for maintaining individual health. Any disruption in this pathway can have significant consequences, leading to health issues. According to the World Health Organization, an estimated 25% of the global population presents symptoms of anemia. This protocol describes how to generate human erythroid cells both in vitro using hematopoietic stem and progenitor cells (HSPCs) from sources such as umbilical cord blood (UCB) or blood taken from healthy donors and ex vivo with HSPCs isolated from patients' bone marrow. Using genetic approach, genes of interest can be modulated in HSPCs, and their impact on erythropoiesis can be monitored at various stages of the differentiation process. This method allows for the screening of compounds perturbing, enhancing, or rescuing the capacity of HSPCs to differentiate into mature erythroid cells and to investigate the role of genes of interest during the erythroid differentiation process.