Search

Introduction: Total ankle replacement is indicated for end-stage ankle osteoarthritis. Periprosthetic radiolucency, from separation between the bone and implant, is suggested to be indicative of potential prosthesis failure risk. Anchoring implants with cement may mitigate this. This study aimed to compare rates of periprosthetic radiolucency between patients with cement-affixed and cementless implants., Methods: A retrospective analysis was performed on 28 patients who underwent total ankle replacement with the INFINITY Total Ankle System (Wright Medical, Memphis, Tennessee) implant between January 2016 and May 2022. Anteroposterior, mortise, and lateral ankle X-rays were reviewed by 2 independent reviewers for tibiotalar angle, talar tilt, and periprosthetic radiolucency. The Wilcoxon rank-sum test and chi-square test were performed., Results: The incidence of periprosthetic radiolucency at the most recent follow-up did not significantly differ between cement and cementless groups (57.1% in both groups, P = 1.0). Follow-up tibiotalar and talar tilt angles were not significantly different (P > .51 for all comparisons)., Conclusions: Patients with cemented implants had a similar incidence of periprosthetic radiolucency compared with patients with cementless prostheses. Understanding of long-term clinical outcomes will help inform optimal operative approaches for ankle prostheses., Levels of Evidence: Therapeutic, Level III, Retrospective cohort study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The degree of metastatic disease varies widely among patients with cancer and affects clinical outcomes. However, the biological and functional differences that drive the extent of metastasis are poorly understood. We analyzed primary tumors and paired metastases using a multifluorescent lineage-labeled mouse model of pancreatic ductal adenocarcinoma (PDAC)-a tumor type in which most patients present with metastases. Genomic and transcriptomic analysis revealed an association between metastatic burden and gene amplification or transcriptional upregulation of MYC and its downstream targets. Functional experiments showed that MYC promotes metastasis by recruiting tumor-associated macrophages, leading to greater bloodstream intravasation. Consistent with these findings, metastatic progression in human PDAC was associated with activation of MYC signaling pathways and enrichment for MYC amplifications specifically in metastatic patients. Collectively, these results implicate MYC activity as a major determinant of metastatic burden in advanced PDAC. SIGNIFICANCE: Here, we investigate metastatic variation seen clinically in patients with PDAC and murine PDAC tumors and identify MYC as a major driver of this heterogeneity. This article is highlighted in the In This Issue feature, p. 275 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Epithelial plasticity, or epithelial-to-mesenchymal transition (EMT), is a well-recognized form of cellular plasticity, which endows tumor cells with invasive properties and alters their sensitivity to various agents, thus representing a major challenge to cancer therapy. It is increasingly accepted that carcinoma cells exist along a continuum of hybrid epithelial-mesenchymal (E-M) states and that cells exhibiting such partial EMT (P-EMT) states have greater metastatic competence than those characterized by either extreme (E or M). We described recently a P-EMT program operating in vivo by which carcinoma cells lose their epithelial state through post-translational programs. Here, we investigate the underlying mechanisms and report that prolonged calcium signaling induces a P-EMT characterized by the internalization of membrane-associated E-cadherin (ECAD) and other epithelial proteins as well as an increase in cellular migration and invasion. Signaling through Gαq-associated G-protein-coupled receptors (GPCRs) recapitulates these effects, which operate through the downstream activation of calmodulin-Camk2b signaling. These results implicate calcium signaling as a trigger for the acquisition of hybrid/partial epithelial-mesenchymal states in carcinoma cells., (© 2021 The Authors.)