The latest medical research on Pancreatic Cancer

This prospective randomized controlled study was conducted to evaluate the safety and efficacy of the Pringle hepatic hilar occlusion with a bulldog clamp in laparoscopic liver resection.

From March 1, 2020 to July 31, 2021, 80 patients were enrolled, including 40 undergoing intraperitoneal Pringle maneuver (IPM) and 40 extraperitoneal Pringle maneuver (EPM). The observation indices included basic preoperative clinical characteristics and intraoperative and postoperative liver function indices.

There were no significant differences in the basic characteristics or types of hepatectomy, intraoperative blood loss, intraoperative blood transfusion, or hepatectomy time between the IPM and EPM groups. However, the blocking and operation time in the IPM group was shorter than that in the EPM group. There were no significant differences in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels on the first day after surgery or in total bilirubin (TBIL) or albumin (ALB) levels on the first, third, or fifth days after surgery. However, C-reactive protein (CRP) levels on the first and third days, ALT and AST levels on the third and fifth days were lower, and hospital stay after surgery was shorter in the IPM group than in the EPM group.

IPM using bulldog clamps is simple, safe, and effective. The inflammatory reaction is less severe, the degree of liver function injury is lower, and recovery is faster.

Non-hypervascular hypointense nodules (NHHNs) can transform into hypervascular hepatocellular carcinoma (HCC) during the long-term follow-up. However, the risk factors for NHHN hypervascular transformation in chronic hepatitis B virus (HBV)-infected populations are unknown. This study assessed the predictive value of gadoxetic acid-enhanced magnetic resonance imaging (MRI) for HCC development in patients with chronic HBV infection.

A total of 86 patients with HBV infection who underwent gadoxetic acid-enhanced MRI at the First Affiliated Hospital of Sun Yat-sen University between January 2011 and July 2019 and were followed up for 2 years were retrospectively reviewed. Imaging features, including cirrhosis, steatosis, and NHHNs, were collected. Radiomics features were extracted from the entire liver. The HCC development predictive models were built based on each patient's clinical data, MRI features, and radiomic features. We then collected the qualitative and quantitative features of each NHHN and investigated the risk factors of hypervascular transformation.

Thirteen patients developed HCC within two years. The risk factors for HCC development in patients with chronic HBV infection included older age, cirrhosis, and NHHNs. The MRI, radiomics, and integrated models developed all had an area under the curve (AUC) above 0.8. The potential risk factors for hypervascular transformation of NHHNs were the diameter of the NHHN (OR = 1.69, 95% CI:1.23, 2.32, P = 0.001) and the signal intensity (SI) ratio of the NHHN to the liver in the hepatobiliary phase (HBP SI ratio*10, OR = 0.36, 95% CI:0.11, 0.85, P = 0.044). The AUC of the hypervascular transformation model was 0.846 (95% CI:0.719, 0.972).

In chronic HBV infection population, patients with older age, cirrhosis and NHHNs are more likely to develop HCC within two years. Models based on these factors or radiomic features can effectively predict HCC development. The diameter of the NHHNs and the signal intensity ratio of NHHN to the liver in the hepatobiliary phase are potential risk factors for the hypervascular transformation of NHHNs.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, highly resistant to standard chemotherapy and immunotherapy. Regulatory T cells (Tregs) expressing tumor necrosis factor α receptor 2 (TNFR2) contribute to immunosuppression in PDAC. Treg infiltration correlates with poor survival and tumor progression in patients with PDAC. We hypothesized that TNFR2 inhibition using a blocking monoclonal antibody (mAb) could shift the Treg-effector T cell balance in PDAC, thus enhancing antitumoral responses.

To support this hypothesis, we first described TNFR2 expression in a cohort of 24 patients with PDAC from publicly available single-cell analysis data. In orthotopic and immunocompetent mouse models of PDAC, we also described the immune environment of PDAC after immune cell sorting and single-cell analysis. The modifications of the immune environment before and after anti-TNFR2 mAb treatment were evaluated as well as the effect on tumor progression.

Patients with PDAC exhibited elevated TNFR2 expression in Treg, myeloid cells and endothelial cells and lower level in tumor cells. By flow cytometry and single-cell RNA-seq analysis, we identified two Treg populations in orthotopic mouse models: Resting and activated Tregs. The anti-TNFR2 mAb selectively targeted activated tumor-infiltrating Tregs, reducing T cell exhaustion markers in CD8+ T cells. However, anti-TNFR2 treatment alone had limited efficacy in activating CD8+ T cells and only slightly reduced the tumor growth. The combination of the anti-TNFR2 mAb with agonistic anti-CD40 mAb promoted stronger T cell activation, tumor growth inhibition, and improved survival and immunological memory in PDAC-bearing mice.

Our data suggest that combining a CD40 agonist with a TNFR2 antagonist represents a promising therapeutic strategy for patients with PDAC.