Vesiclemia: counting on extracellular vesicles for glioblastoma patients

International audienceAlthough rare, glioblastoma is a devastating tumor of the central nervous system characterized by a poor survival and an extremely dark prognosis, making its diagnosis, treatment, and monitoring highly challenging. Numerous studies have highlighted extracellular vesicles (EVs) as key players of tumor growth, invasiveness, and resistance, as they carry oncogenic material. Moreover, EVs have been shown to communicate locally in a paracrine way but also at remote throughout the organism. Indeed, recent reports demonstrated the presence of brain tumor-derived EVs into body fluids such as plasma and cerebrospinal fluid. Fluid-associated EVs have indeed been suspected to reflect quantitative and qualitative information about the status and fate of the tumor and can potentially act as a resource for noninvasive biomarkers that might assist in diagnosis, treatment, and follow-up of glioblastoma patients. Here, we coined the name vesiclemia to define the concentration of plasmatic EVs, an intuitive term to be directly transposed in the clinical jargon

The von Willebrand Factor stamps Plasmatic Extracellular Vesicles from Glioblastoma Patients

International audienceGlioblastoma is a devastating tumor of the central nervous system characterized by a poor survival and an extremely dark prognosis, making its diagnosis, treatment and monitoring highly challenging. Numerous studies have highlighted extracellular vesicles (EVs) as key players of tumor growth, invasiveness and resistance, as they carry and disseminate oncogenic material in the local tumor microenvironment and at distance. However, whether their quality and quantity reflect individual health status and changes in homeostasis is still not fully elucidated. Here, we separated EVs from plasma collected at different time points alongside with the clinical management of GBM patients. Our findings confirm that plasmatic EVs could be separated and characterized with standardized protocols, thereby ensuring the reliability of measuring vesiclemia, i.e . extracellular vesicle concentration in plasma. This unveils that vesiclemia is a dynamic parameter, which could be reflecting tumor burden and/or response to treatments. Further label-free liquid chromatography tandem mass spectrometry unmasks the von Willebrand Factor (VWF) as a selective protein hallmark for GBM-patient EVs. Our data thus support the notion that EVs from GBM patients showed differential protein cargos that can be further surveyed in circulating EVs, together with vesiclemia

To Drain or Not to Drain Infraperitoneal Anastomosis After Rectal Excision for Cancer

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Surgical Management of Retrorectal Tumors A French Multicentric Experience of 270 Consecutives Cases

International audienceObjective: To report the largest multicentric experience on surgical management of retrorectal tumors (RRT). Background: Literature data on RRT is limited. There is no consensus concerning the best surgical approach for the management of RRT. Methods: Patients operated for RRT in 18 academic French centers were retrospectively included (2000-2019). Results: A total of 270 patients were included. Surgery was performed through abdominal (n = 72, 27%), bottom (n = 190, 70%), or combined approach (n = 8, 3%). Abdominal approach was laparoscopic in 53/72 (74%) and bottom approach was Kraske modified procedures in 169/190 (89%) patients. In laparoscopic abdominal group, tumors were more frequently symptomatic (37/53, 70% vs 88/169, 52%, P = 0.02), larger [mean diameter = 60.5 +/- 24 (range, 13-107) vs 51 +/- 26 (20-105) mm, P = 0.02] and located above S3 vertebra (n = 3/42, 7% vs 0%, P = 0.001) than those from Kraske modified group. Laparoscopy was associated with a higher risk of postoperative ileus (n = 4/53, 7.5% vs 0%, P = 0.002) and rectal fistula (n = 3/53, 6% vs 0%, P=0.01) but less wound abscess (n = 1/53, 2% vs 24/169, 14%, P = 0.02) than Kraske modified procedures. RRT was malignant in 8%. After a mean follow up of 27 +/- 39 (1-221) months, local recurrence was noted in 8% of the patients. After surgery, chronic pain was observed in 17% of the patients without significant difference between the 2 groups (15/74, 20% vs 3/30, 10%; P = 0.3). Conclusions: Both laparoscopic and Kraske modified approaches can be used for surgical treatment of RRT (according to their location and their size), with similar long-term results

Discovery of DNA methylation signature in the peripheral blood of individuals with history of antenatal exposure to valproic acid

PURPOSE: Valproic acid or valproate is an effective antiepileptic drug; however, embryonic exposure to valproate can result in a teratogenic disorder referred to as fetal valproate syndrome (FVS, OMIM #609442). Currently there are no diagnostic biomarkers for the condition. This study aims to define an episignature biomarker for teratogenic antenatal exposure to valproate.METHODS: DNA extracted from peripheral blood of individuals with teratogenic antenatal exposure to valproate was processed using DNA methylation microarrays. Subsequently, methylation profiling and construction of support vector machine classifiers were performed in R.RESULTS: Genomic DNA methylation analysis was applied, and a distinct DNA methylation profile was identified in the majority of affected individuals. This profile was used to develop a diagnostic episignature classifier. The valproate exposure episignature exhibited high sensitivity and specificity relative to a large reference dataset of unaffected controls and individuals with a wide spectrum of syndromic disorders with episignatures. Gene set enrichment analysis demonstrated an enrichment for terms associated with cell adhesion, including significant overrepresentation of the cadherin superfamily.CONCLUSION: This study provides evidence of a robust peripheral blood-based diagnostic epigenetic biomarker for a prenatal teratogenic disorder.</p

Lessons from two series by physicians and caregivers' self‐reported data in DDX3X ‐related disorders

International audienceAbstract Introduction and Methods We report two series of individuals with DDX3X variations, one (48 individuals) from physicians and one (44 individuals) from caregivers. Results These two series include several symptoms in common, with fairly similar distribution, which suggests that caregivers' data are close to physicians' data. For example, both series identified early childhood symptoms that were not previously described: feeding difficulties, mean walking age, and age at first words. Discussion Each of the two datasets provides complementary knowledge. We confirmed that symptoms are similar to those in the literature and provides more details on feeding difficulties. Caregivers considered that the symptom attention‐deficit/hyperactivity disorder were most worrisome. Both series also reported sleep disturbance. Recently, anxiety has been reported in individuals with DDX3X variants. We strongly suggest that attention‐deficit/hyperactivity disorder, anxiety, and sleep disorders need to be treated

Limited Resection Versus Pancreaticoduodenectomy for Duodenal Gastrointestinal Stromal Tumors? Enucleation Interferes in the Debate: A European Multicenter Retrospective Cohort Study

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