Volumetric graft changes after liver transplantation: evidence of adaptation to recipient body size.

It is believed that whole liver grafts adjust their size to fit the body size of the recipient after transplantation, despite a lack of evidence. The aim of this study was to test this hypothesis. This was a retrospective cohort study of 113 liver transplantations performed at Karolinska University Hospital. The cohort was divided based on graft volume-to-standard liver volume ratio (GV/SLV) into quartiles of small, mid, and large grafts. Serial volumetric assessment was performed on the day of transplantation and at posttransplant check-ups early (<2 mo) and late (9-13 mo) after transplantation using computed tomography (CT) volumetry. Change in GV/SLV ratio over time was analyzed with ANOVA repeated measures. A multiple regression model was used to investigate the influence of intraoperative blood flow, recipient body size, age, and relative sickness on graft volume changes. Between the three time points, mean GV/SLV ratio adapted to 0.55-0.94-1.00 in small grafts (n = 29, P < 0.001); 0.87-1.18-1.13 in midgrafts (n = 56, P < 0.001); 1.11-1.51-1.18 in large grafts (n = 28, P < 0.001). Regression analysis showed a positive correlation between posttransplant graft growth and portal flow (ß = 1.18, P = 0.005), arterial flow (ß = 0.17, P = 0.001), and recipient body surface area (ß = 59.85, P < 0.001). A negative correlation was observed for graft weight-to-recipient weight ratio (GRWR; ß = -33.12, P < 0.001). Grafts with initial GV/SLV-ratio < 0.6 adapt toward the ideal volume for recipient body size 1 year after transplantation. The disparity between graft size relative to recipient body size, and the portal and arterial perfusion, influence volumetric graft changes.NEW & NOTEWORTHY This is the first and largest human study to verify the hypothesis that whole liver grafts adjust their size to match recipient body size 1 year after transplantation-a phenomenon that has previously only been observed in experimental animal studies and human case reports. The direction of volumetric changes is driven by the disparity between graft size relative to recipient body surface area and weight, as well as the intraoperative portal- and arterial graft perfusion.

Chromatin Interactions and Regulatory Elements in Cancer: From Bench to Bedside.

Chromatin interactions regulate gene expression by bringing distal regulatory elements, such as super-enhancers, to promoters in close spatial proximity. It has been recognized that in cancer, chromatin interactions can be dysregulated, leading to aberrant oncogene expression. Chromatin interactions may potentially serve as biomarkers, or be modulated via CRISPR therapy and small molecule inhibitors against transcription. However, these methods face challenges that must be resolved and raise questions for further research. Understanding chromatin interactions is essential for safety aspects of anticancer therapies, such as the mechanism of action of epigenetic regulators and transcription factors in cancer, and potential off-target effects arising from targeting super-enhancers and promoters. In this review article, we discuss how chromatin interactions and regulatory elements may become dysregulated in cancer, potential methods to target them for clinical therapy, and outline outstanding questions that require addressing before epigenetic therapies can translate to the clinic safely and effectively.