Hepatocellular Carcinoma: Current Drug Therapeutic Status, Advances and Challenges.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for ~90% of liver neoplasms. It is the second leading cause of cancer-related deaths and the seventh most common cancer worldwide. Although there have been rapid developments in the treatment of HCC over the past decade, the incidence and mortality rates of HCC remain a challenge. With the widespread use of the hepatitis B vaccine and antiviral therapy, the etiology of HCC is shifting more toward metabolic-associated steatohepatitis (MASH). Early-stage HCC can be treated with potentially curative strategies such as surgical resection, liver transplantation, and radiofrequency ablation, improving long-term survival. However, most HCC patients, when diagnosed, are already in the intermediate or advanced stages. Molecular targeted therapy, followed by immune checkpoint inhibitor immunotherapy, has been a revolution in HCC systemic treatment. Systemic treatment of HCC especially for patients with compromised liver function is still a challenge due to a significant resistance to immune checkpoint blockade, tumor heterogeneity, lack of oncogenic addiction, and lack of effective predictive and therapeutic biomarkers.

The impact of elective surgery postponement during COVID-19 on emergency bellwether procedures in a large tertiary centre in Singapore.

The coronavirus disease 2019 (COVID-19) pandemic drove many healthcare systems worldwide to postpone elective surgery to increase healthcare capacity, manpower, and reduce infection risk to staff. The aim of this study was to assess the impact of an elective surgery postponement policy in response to the COVID-19 pandemic on surgical volumes and patient outcomes for three emergency bellwether procedures. A retrospective cohort study of patients who underwent any of the three emergency procedures [Caesarean section (CS), emergency laparotomy (EL), and open fracture (OF) fixation] between 1 January 2018 and 31 December 2021 was conducted using clinical and surgical data from electronic medical records. The volumes and outcomes of each surgery were compared across four time periods: pre-COVID (January 2018-January 2020), elective postponement (February-May 2020), recovery (June-November 2020), and postrecovery (December 2020-December 2021) using Kruskal-Wallis test and segmented negative binomial regression. There was a total of 3886, 1396, and 299 EL, CS, and OF, respectively. There was no change in weekly volumes of CS and OF fixations across the four time periods. However, the volume of EL increased by 47% [95% confidence interval: 26-71%, P = 9.13 × 10-7) and 52% (95% confidence interval: 25-85%, P = 3.80 × 10-5) in the recovery and postrecovery period, respectively. Outcomes did not worsen throughout the four time periods for all three procedures and some actually improved for EL from elective postponement onwards. Elective surgery postponement in the early COVID-19 pandemic did not affect volumes of emergency CS and OF fixations but led to an increase in volume for EL after the postponement without any worsening of outcomes.

Presence of onco-fetal neighborhoods in hepatocellular carcinoma is associated with relapse and response to immunotherapy.

Onco-fetal reprogramming of the tumor ecosystem induces fetal developmental signatures in the tumor microenvironment, leading to immunosuppressive features. Here, we employed single-cell RNA sequencing, spatial transcriptomics and bulk RNA sequencing to delineate specific cell subsets involved in hepatocellular carcinoma (HCC) relapse and response to immunotherapy. We identified POSTN+ extracellular matrix cancer-associated fibroblasts (EM CAFs) as a prominent onco-fetal interacting hub, promoting tumor progression. Cell-cell communication and spatial transcriptomics analysis revealed crosstalk and co-localization of onco-fetal cells, including POSTN+ CAFs, FOLR2+ macrophages and PLVAP+ endothelial cells. Further analyses suggest an association between onco-fetal reprogramming and epithelial-mesenchymal transition (EMT), tumor cell proliferation and recruitment of Treg cells, ultimately influencing early relapse and response to immunotherapy. In summary, our study identifies POSTN+ CAFs as part of the HCC onco-fetal niche and highlights its potential influence in EMT, relapse and immunotherapy response, paving the way for the use of onco-fetal signatures for therapeutic stratification.