Neuroendocrine Tumors of Meckel’s Diverticulum: Lessons from a Single Institution Study of Eight Cases

Introduction  

Endocrine tumors of Meckel’s diverticulum are rare. Their clinical and pathological characteristics are not well known, making it difficult to assess the best strategy for therapeutic management.     

Array-Based Genomics in Glioma Research

Over the years, several relevant biomarkers with a potential clinical interest have been identified in gliomas using various techniques, such as karyotype, microsatellite analysis, fluorescent in situ hybridization and chromosome comparative genomic hybridization. Despite their pivotal contribution to our understanding of gliomas biology, clinical application of these approaches has been limited by technological and clinical complexities. In contrast, genomic arrays (array-based comparative genomic hybridization and single nucleotide polymorphisms array) have emerged as promising technologies for clinical use in the setting of gliomas. Indeed, their feasibility and reliability have been rigorously assessed in gliomas and are discussed in this review. The well-known genomic biomarkers in gliomas are in fact readily and reliably identified using genomic arrays. Moreover, it detects a multitude of new cryptic genomic markers, with potential biological and/or clinical significances. The main studies dedicated to genomic characterization of gliomas using genomic arrays are reviewed here. Interestingly, several recurrent genomic signatures have been reported by different teams, suggesting the validity of these genomic patterns. In light of this, genomic arrays are relatively simple and cost-effective techniques whose implementation in molecular diagnostic laboratories should be encouraged as a valuable clinical tool for management of glioma patients.     

Refractory status epilepticus: Electroconvulsive therapy as a possible therapeutic strategy

Refractory status epilepticus (SE) is a current daily therapeutic challenge. Electroconvulsive therapy (ECT), which is frequently used to treat psychiatric disorders, is known to raise the seizure threshold. As such, ECT could be of major interest in refractory SE. In this paper, we provide a brief overview of ECT in refractory SE. Although no placebo-controlled or open-label study has been published on the efficacy or safety of ECT in refractory SE, eight case reports have been identified. SE cessation was obtained in 80% of cases, and complete recovery was achieved in 27% of patients. Despite the heterogeneity of the ECT parameters used in these articles, we identified some common features that may be recommended for the use of ECT in refractory SE. ECT might be a viable therapeutic strategy for the most resistant and severe cases of SE, particularly after the failure of two inductions of anesthetic coma. This potential indication highlights the urgent need for clinical trials that assess the usefulness of ECT in refractory SE.     

Variability of Voriconazole Plasma Concentrations after Allogeneic Hematopoietic Stem Cell Transplantation: Impact of Cytochrome P450 Polymorphisms and Comedications on Initial and Subsequent Trough Levels

Voriconazole (VRC) plasma trough concentrations (C_min) are highly variable, and this could affect treatment efficacy and safety in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). We aimed to describe the intra- and interindividual variation of VRC C_min throughout the course of VRC therapy and to identify the determinants of this variation. Clinical data, medications, and VRC C_min (n = 308) of 33 AHSCT patients were retrospectively collected. Cytochrome P450 (CYP450) genotypes of CYP2C19, CYP3A4, and CYP3A5 patients were retrospectively determined before allografting, and a combined genetic score was calculated for each patient. The higher the genetic score, the faster the metabolism of the patient. The VRC C_min inter- and intraindividual coefficients of variation were 84% and 68%, respectively. The VRC dose (D) was correlated to VRC C_min (r = 0.412, P < 0.0001) only for oral administration. The administration route and the genetic score significantly affected the initial VRC C_min. Considering oral therapy, patients with a genetic score of <2 had higher initial VRC C_min/D than patients with a genetic score of >2 (P = 0.009). Subsequent VRC C_min remained influenced by the genetic score (P = 0.004) but were also affected by pump proton inhibitor comedication (P < 0.0001). The high variability of VRC C_min in AHSCT patients is partially explained by the route of administration, treatment with pump proton inhibitors, and the combined genetic score. This study suggests the interest in combined genetic score determination to individualize a priori the VRC dose and underlines the need for longitudinal therapeutic drug monitoring to adapt subsequent doses to maintain the VRC C_min within the therapeutic range.