The steatotic liver disease (SLD) landscape has seen a paradigm shift in recent years with a revitalization of the nomenclature following a multi-society Delphi consensus. The terms metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) were introduced to address several of the challenges and limitations associated with the former terminology. By transitioning away from stigmatizing and ambiguous terms, the nomenclature has adopted inclusionary language that emphasizes the underlying risk factors that drive disease progression and are accompanied by distinct diagnostic criteria. With SLD prevalence steadily increasing over the past few decades, affecting over 30% of the global population, accurate classification of the spectrum of conditions that fall under this overarching term is essential. Most importantly, the introduction of combined metabolic and alcohol-associated liver disease (MetALD) as a novel subclassification of SLD has shifted the diagnostic approach, raised awareness of disease prevalence, and paved the way for therapeutic management and multidisciplinary approaches to patient care. By recognizing the distinct clinical entity that is MetALD and the synergistic interplay between the cardiometabolic risk factors and alcohol use, clinicians are better equipped to effectively care for this patient population. In this review, we aim to discuss the catalysts for the SLD nomenclature changes, the dynamic nature of its subclasses, the natural history and disease burden, and the implications for clinical practice and research, with a particular focus on MetALD.

Tumor location affects rectal cancer management, but no consensus exists on criteria. The anterior peritoneal reflection (aPR), an anatomical landmark, shows potential for defining tumor location but requires clinical validation. This study evaluated the utility of aPR in guiding neoadjuvant chemoradiotherapy (nCRT) decisions and predicting lateral lymph node (LLN)/distant metastasis patterns. This single-center retrospective cohort analyzed data from Peking Union Medical College Hospital (Beijing, China) between January 2016 and August 2022. Magnetic resonance imaging (MRI)-measured aPR parameters were pathologically validated. Patients were stratified by aPR-based definition and tumor height (10 cm). Kaplan-Meier survival curves, log-rank tests, and Cox regression were used for prognostic analysis. Among 588 patients (439 tumors ≥5 cm from the anal verge), MRI identified aPR with an accuracy of 95.4%. For tumors ≥5 cm, aPR-defined middle-to-low rectal cancer showed lower 3-year disease-free survival (DFS) rate than the upper rectal cancer (P = 0.010), while their 3-year overall survival (OS) rates were comparable. Conversely, 10-cm-defined classification showed no DFS or OS differences (both P > 0.2). Cox regression confirmed aPR-defined classification as an independent DFS predictor (HR = 3.19, P = 0.014), while 10-cm classification was non-predictive. nCRT with tumor regression grade (TRG) 0-1 trended toward improved DFS compared with direct surgery (HR = 0.56, P = 0.072). The independent protective effect of nCRT with TRG 0-1 for DFS was exclusive to the aPR-defined middle-to-low rectal cancer subgroup (HR = 0.45, P = 0.026) and not observed in the 10-cm subgroup. aPR-defined classification was independently associated with LLNs on MRI and postoperative pulmonary metastasis. aPR may guide nCRT decision-making and predict LLN metastasis and postoperative distant organ metastasis.

BackgroundAccording to the Global Cancer Observatory 2020 report, pancreatic cancer occupies the 11th position among the leading causes of cancer-related mortality in both sexes, with nearly 500,000 deaths annually worldwide. This study aimed to evaluate the trend of mortality due to pancreatic cancer in Montenegro from 1990 to 2018 and to contribute to the effective planning of preventive strategies for pancreatic cancer as well as future health policies and initiatives.MethodsWe utilized national data on the causes of death from pancreatic cancer and codes 157 from the 9th and C25 from the 10th revision of the International Classification of Diseases. The trend was described by using Joinpoint, Poisson, and linear regression.ResultsMortality rates of pancreatic cancer in Montenegro consistently increased (P < 0.05) for the overall level for both men and women, with the average annual percentage change (AAPC) in the AAPC order (95% confidence interval): 1.7% (0.9%–2.5%) overall, 1.3% (0.4%–2.1%) in men, and 2.2% (0.9%–3.5%) in women. The majority of those who died from pancreatic cancer were aged 65–74 years (32.7%), 55–64 years (26.3%), and 75–84 years (24.1%).ConclusionsThe persistent increase in pancreatic cancer mortality rates in Montenegro, observed in both men and women, highlights a concerning public health trend. With the highest proportion of deaths occurring among individuals aged 55–84 years, these findings underscore the urgent need for policymakers to implement a national strategy targeting early detection, prevention, and improved management, especially among the most affected age groups.

BackgroundThere is no consensus on the adjuvant treatment regimen for patients with colorectal cancer liver metastasis (CRLM) who have achieved successful conversion after surgery. This study aimed to compare the efficacy and safety of chemotherapy alone (CA) versus chemotherapy plus targeted therapy (CT) as adjuvant therapy for CRLM patients.MethodsInitially unresectable CRLM patients who were converted to hepatectomy with no evidence of disease between June 2013 and June 2020 were retrospectively analysed. The baseline characteristics were balanced between the CA and CT cohorts by using 1:2 propensity score matching (PSM). After PSM, disease-free survival (DFS) and overall survival (OS) were evaluated. A comprehensive subgroup analysis compared the efficacy between the cohorts, with DFS and OS assessed by using a stratified log-rank test and summarized by using Kaplan–Meier and Cox proportional hazards methods.ResultsAfter PSM, 66 CA and 132 CT patients were included. DFS and OS were similar between the CA and CT cohorts (median DFS: 8.5 vs 10.8 months; median OS: 51.7 vs 56.5 months; both P > 0.050). In the CT cohort, subgroup analysis indicated a favorable trend of DFS for patients with KRAS/NRAS/BRAF mutations and receiving up to four cycles of conversion therapy (P_interaction, 0.005 and 0.013, respectively). In the KRAS/NRAS/BRAF-mutated cohort, CT significantly improved median DFS compared with CA (11.3 vs 7.4 months; hazard ratio, 0.42; 95% confidence interval, 0.26–0.69; P < 0.001).ConclusionCT, as adjuvant therapy, effectively reduced intrahepatic and extrahepatic recurrence in initially unresectable CRLM patients. The patients with KRAS/NRAS/BRAF mutations or undergoing up to four cycles of conversion therapy benefited more from CT than from CA.

BackgroundPancreatic angiosarcoma is a rare and highly aggressive tumor originating from lymphatic or vascular endothelial cells, with poor prognosis and few effective treatments. In this study, we aimed to characterize the tumor ecosystem of metastatic pancreatic angiosarcoma, along with its potential treatment strategies.MethodsSingle-cell RNA-sequencing and bioinformatics analysis were performed on samples obtained from one patient, including at total of 16,841 cells from pancreatic angiosarcoma liver metastasis and adjacent normal liver tissue.ResultsPancreatic angiosarcoma cells exhibited marked upregulation of nuclear factor kappa-B (NF-κB), hypoxia-inducible factor 1 (HIF-1), and myelocytomatosis oncogene (MYC) proto-oncogene signaling pathways, while presenting limited upregulation of actionable therapeutic targets except for cyclin-dependent kinase 4 (CDK4) and epidermal growth factor receptor. Several immune checkpoint genes, including cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), programmed cell death protein 1 (PDCD1), and cluster of differentiation 86 (CD86), were upregulated in tumor-infiltrating T cells, natural killer (NK) cells, and myeloid cells. Furthermore, intercellular interaction profiling demonstrated enhanced activity of the programmed death-ligand 1 (PD-L1) and CD86 signaling pathways within the tumor microenvironment. The gene-set scores of T/NK-cell exhaustion, regulatory T cell, and macrophage angiogenesis were significantly higher in tumor tissues compared with adjacent normal tissues. However, the phagocytosis scores of macrophages within the tumor-infiltrating region were significantly lower than those in the adjacent normal tissues.ConclusionsOur findings outlined an immunosuppressive and angiogenic tumor ecosystem in pancreatic angiosarcoma liver metastasis, suggesting that pancreatic angiosarcoma may be insensitive to most targeted therapies. Conversely, immunotherapies targeting LAG3, PD-L1, and CD86 (e.g. isatuximab, Opdualag, and abatacept) and anti-angiogenic agents may be therapeutically effective and worthy of subsequent exploration.