Immunotherapy as a Complement to Surgical Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor in adults, and the fourth leading cause of cancer-related deaths worldwide. While surgical and ablative therapies remain the standard of care in early localized disease, late presentation with advanced stages of disease, impaired hepatic function, or local recurrence following surgical resection preclude operative management as the sole treatment modality in a subgroup of patients. As such, systemic therapies, namely immunotherapy, have become an integral part of the HCC treatment algorithm over the past decade. While agents, such as atezolizumab/bevacizumab, have well-established roles as first-line systemic therapy in intermediate- and advanced-stage HCC, the role of immunotherapy in disease amenable to surgical management continues to evolve. In this review, we will discuss the current evidence and aggregate impact of immunotherapy in the context of HCC amenable to surgical management, including its application in the neoadjuvant and adjuvant settings.

Safety of postdischarge extended venous thromboembolism prophylaxis after hepatopancreatobiliary surgery.

BACKGROUND: The risk of venous thromboembolism (VTE) after hepatopancreatobiliary (HPB) surgery is high. Extended postdischarge prophylaxis in this patient population has been controversial. This study aimed to examine the safety of postdischarge extended VTE prophylaxis in patients at high risk of VTE events after HPB surgery. METHODS: Adult patients risk stratified as very high risk of VTE who underwent HPB operations between 2014 and 2020 at a quaternary care center were included. Patients were matched 1:2 extended VTE prophylaxis to the control group (patients who did not receive extended prophylaxis). Analyses compared the proportions of adverse bleeding events between groups. RESULTS: A total of 307 patients were included: 103 in the extended prophylaxis group and 204 in the matched control group. Demographics were similar between groups. More patients in the extended VTE prophylaxis group had a history of VTE (9% vs 3%; P = .045). There was no difference in bleeding events between the extended VTE prophylaxis and the control group (6% vs 2%; P = .091). Of the 6 patients with bleeding events in the VTE prophylaxis group, 5 had gastrointestinal (GI) bleeding, and 1 had hemarthrosis. Of the 4 patients with bleeding events in the control group, 1 had intra-abdominal bleeding, 2 had GI bleeding, and 1 had intra-abdominal and GI bleeding. CONCLUSION: Patients discharged with extended VTE prophylaxis after HPB surgery did not experience more adverse bleeding events compared with a matched control group. Routine postdischarge extended VTE prophylaxis is safe in patients at high risk of postoperative VTE after HPB surgery.

Heat shock protein 104 (Hsp104)-mediated curing of [PSI+] yeast prions depends on both [PSI+] conformation and the properties of the Hsp104 homologs.

Prions arise from proteins that have two possible conformations: properly folded and non-infectious or misfolded and infectious. The [PSI+] yeast prion, which is the misfolded and self-propagating form of the translation termination factor eRF3 (Sup35), can be cured of its infectious conformation by overexpression of Hsp104, which helps dissolve the prion seeds. This dissolution depends on the trimming activity of Hsp104, which reduces the size of the prion seeds without increasing their number. To further understand the relationship between trimming and curing, trimming was followed by measuring the loss of GFP-labeled Sup35 foci from both strong and weak [PSI+] variants; the former variant has more seeds and less soluble Sup35 than the latter. Overexpression of Saccharomyces cerevisiae Hsp104 (Sc-Hsp104) trimmed the weak [PSI+] variants much faster than the strong variants and cured the weak variants an order of magnitude faster than the strong variants. Overexpression of the fungal Hsp104 homologs from Schizosaccharomyces pombe (Sp-Hsp104) or Candida albicans (Ca-Hsp104) also trimmed and cured the weak variants, but interestingly, it neither trimmed nor cured the strong variants. These results show that, because Sc-Hsp104 has greater trimming activity than either Ca-Hsp104 or Sp-Hsp104, it cures both the weak and strong variants, whereas Ca-Hsp104 and Sp-Hsp104 only cure the weak variants. Therefore, curing by Hsp104 overexpression depends on both the trimming ability of the fungal Hsp104 homolog and the strength of the [PSI+] variant: the greater the trimming activity of the Hsp104 homolog and the weaker the variant, the greater the curing.