FGFR2 residence in primary cilia is necessary for epithelial cell signaling

5 May

A Systematic Review of Current Terminology for Conditions Preceding Degenerative Cervical Myelopathy: Evidence Synthesis to Inform an AO Spine Expert Opinion Statement

Study DesignSystematic review.ObjectivesThe pre-symptomatic state of Degenerative Cervical Myelopathy (DCM), wherein degenerative changes and spinal cord compression are seen without clinical findings, is poorly understood and inconsistently categorised. Clear identification may elucidate the temporality of DCM development. Therefore, a systematic assessment was undertaken of current terminology for pre-DCM states, with the objective of standardising definitions and informing an AO Spine expert position statement.MethodsMedline and Embase were searched for all studies on asymptomatic spinal compression or clinical findings preceding DCM, returning 3585 studies. After screening, 96 studies were included in the final analysis. The terminology used for pre-DCM states and their definitions were extracted, along with their frequencies or speciality/country of author in the literature.ResultsMultiple terms were used to represent pre-DCM stages, including "asymptomatic" (86 studies), "non-myelopathic" (26 studies), "without myelopathy" (15 studies), "pre-symptomatic" (9 studies) and "sub-clinical" (7 studies). "asymptomatic" was associated with the greatest inconsistency. Some defined this as patients with radiological signs of spinal degeneration with/without spinal cord compression but no clinical signs of myelopathy, whereas others used the term synonymously with healthy controls.

5 May

Search for Mutations Connected With Non-Response to Anti-EGFR Therapy in mCRC in the Morphologically Defined Regions of Primary Tumours

Background: Emerging evidence suggests that tumour morphological heterogeneity may influence mutational profiles relevant to therapy response. In this pilot study, we aimed to assess whether mutations identified within specific morphological patterns or at the invasion front correlate with shorter time to progression after anti-EGFR therapy, as compared to whole-tissue analysis.

Methods: We investigated genetic mutations in 142 samples from primary tumours of 39 KRAS wild-type metastatic colorectal cancer (CRC) patients receiving anti-EGFR therapy. Deep next-generation sequencing was performed on whole-tumour sections and six morphology-defined tumour regions.

Results: Mutations in genes linked to anti-EGFR therapy response (KRAS, BRAF, NRAS, PTEN and PI3KCA) were found uniquely in the non-responder group, with substantial variability across morphological sub-regions. BRAF mutations were aligned with serrated and mucinous morphologies, while KRAS mutations (p.Lys147Glu and p.Ala146Thr) were associated with mucinous and desmoplastic morphologies. In all cases, the cumulative mutational profile from sub-regions provided more details than that of the whole-tumour profile.