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.

A scoping review of unexpected weight loss and cancer: risk, guidelines, and recommendations for follow-up in primary care.

BACKGROUND: Cancer diagnoses often begin with consultations with general practitioners (GPs), but the nonspecific nature of symptoms can lead to delayed diagnosis. Unexpected weight loss (UWL) is a common nonspecific symptom linked to undiagnosed cancer, yet guidelines for its diagnostic assessment in general practice lack consistency. AIM: To synthesise evidence on the association between UWL and cancer diagnosis, and to review clinical guidelines and recommendations for assessing patients with UWL. DESIGN AND SETTINGS: Systematic search and analysis of studies conducted in primary care. METHOD: Four databases searched for peer-reviewed literature from 2012 to 2023. Two reviewers conducted all the steps. A narrative review was conducted detailing the evidence for UWL as a risk factor for undiagnosed cancer, existing clinical guidance, and recommended diagnostic approach. RESULTS: We included 25 studies involving 916,092 patients; 92% provided strong evidence of an association between UWL and undiagnosed cancer. The National Institute for Health Care and Excellence Cancer Guideline in the UK was frequently cited. General suggestions encompassed regular weight monitoring, family history, risk factor evaluation, additional signs and symptoms, and a comprehensive physical examination. Commonly recommended pathology tests included C-reactive protein, complete blood count, alkaline phosphatase, and thyroid-stimulating hormone. Immunochemical faecal occult blood test, abdominal ultrasound, and chest X-ray were also prevalent. One large cohort study provided age, sex, and differential diagnosis-specific recommendations. CONCLUSION: This evidence review informs recommendations for investigating patients with UWL and will contribute to a computer decision support tool implementation in primary care, enhancing UWL assessment and potentially facilitating earlier cancer diagnosis.