Systemic inflammation and immune dysfunction have been proved to be associated with cancer progression and metastasis in various malignancies. The aim of this retrospective study was to evaluate the prognostic significance of pre-treatment systemic immune-inflammation index (SII) in patients with advanced pancreatic cancer. In total, 419 patients diagnosed with advanced pancreatic cancer, between January 2011 and December 2015, were retrospectively enrolled. The SII was developed based on a training set of 197 patients from 2011 to 2013 and validated in an independent cohort of 222 patients from 2014 to 2015. Data on baseline clinicopathologic characteristics; pre-treatment laboratory variables such as absolute neutrophil, lymphocyte, and platelet counts; and carbohydrate antigen 19-9 (CA19-9), total bilirubin (TBIL), albumin (ALB), alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) levels were collected. The association between clinicopathologic characteristics and SII was assessed. The overall survival was calculated using the Kaplan–Meier survival curves and compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression models were used to analyze the prognostic value of the SII. An optimal cutoff point for the SII of 440 stratified the patients with advanced pancreatic cancer into high (> 440) and low (≤ 440) SII groups in the training cohort. Univariate and multivariate analyses revealed that the SII was an independent predictor for overall survival. The prognostic significance of the SII was confirmed in both normal and elevated CA19-9 levels. The baseline SII serves as an independent prognostic marker for patients with advanced pancreatic cancer and can be used in patients with both normal and elevated CA19-9 levels.

Background: Gallbladder carcinoma is the most common cancer of the biliary tract, and the immune checkpoint blockade showed promising efficacy in the treatment of advanced gallbladder carcinoma. However, the underlying mechanisms remain unknown. Methods: Single-cell RNA sequencing was used to reveal immune cell dynamics in an anti-PD-1 responder with gallbladder carcinoma liver metastases. Gene set variation analysis, pseudotime analysis, single-cell regulatory network inference and clustering analysis, and CellChat analysis were used to identify the functions of each cell cluster. Immunohistochemistry and multicolored immunohistochemistry analysis were applied to confirm the intratumoral cell types, and the prognostic value of CXCL13+CD8+T cells in patients with gallbladder carcinoma liver metastases with immunotherapy was evaluated. Four biliary tract carcinoma and 3 immunotherapy bulk RNA-seq datasets were analyzed to investigate the prognostic value of CXCL13+CD8+T cells and SPP1+TAMs. Result: A total of 19,648 high-quality single-cell transcriptome data were obtained from liver metastasis before and after aPD-1 therapy. We discovered improved cytotoxic activity in CD8+T cells and enhanced proinflammatory phenotypes in myeloid cells. The identified SPP1+TAMs were related to poor prognosis. The increased effector/memory T cells represented characteristics similar to exhausted T cells in transitory status after aPD-1therapy, which may play a crucial role in the antitumor immune response. We further revealed that CXCL13+T cells in a high subtype of biliary tract carcinoma were characterized as a ‘hot tumor’ profile with high immune scores, correlated to the immunostimulatory context with favorable survival, and can predict effective responses to immunotherapy. Conclusions: Our study provided an overview of immune cell dynamics in gallbladder carcinoma liver metastases after aPD-1 treatment and highlighted the importance of CXCL13+T cells in biliary tract carcinoma and effective responses to immunotherapy, which would advance the understanding and treatment of the disease.

The co-delivery of multiple drugs using nanocarriers has been recognized as a promising strategy for cancer treatment to enhance therapeutic efficacy. In this study, a monodisperse mesoporous silica nanoparticle (mSiO₂) is prepared and functionalized into high-efficiency loaded Lenvatinib and Bufalin for targeted delivery to Cholangiocarcinoma (CCA). mSiO₂ was synthesized on solid silica nanoparticles by oil–water interface method, and highly monodisperse mSiO₂ with uniform morphology was obtained. mSiO₂ was then sequentially modified by polyethylene glycol (PEG) and the targeting molecule folic acid (FA). mSiO₂-FA was designed as co-delivery system for Lenvatinib (Le) and Bufalin (Bu) to increase drug availability and highly target tumor cells. Compared with unfunctionalized mSiO₂, mSiO₂-FA can more efficiently enter human CCA cell lines (9810 cells) and enhance intracellular drug delivery. Moreover, drug-loaded mSiO₂-FA (Le/Bu@mSiO₂-FA) significantly inhibited the viability, migration and invasion of 9810 cells. In vivo, the nanocomplex significantly reduced the tumor load in CCA tumor-bearing mouse models compared to Le or Bu alone. The current work provides a useful strategy for highly targeted and multidrug-resistance reversal therapy for CCA.

Pancreatic cancer is one of the most malignant tumors with an inferior prognosis. This study aims to determine the prognostic significance of immune-inflammatory scores and coagulation indices in patients with metastatic pancreatic cancer(MPC) and develop a predictive nomogram. This study retrospectively analyzed the clinical data of 384 patients with MPC who underwent intra-arterial infusion chemotherapy (IAIC). Patients were randomly divided into training and validation cohorts. Firstly, the optimal cutoff values for continuous variables were obtained in the training cohort. Then, survival analysis was performed to evaluate the impact of immune-inflammatory scores neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and coagulation indicators prothrombin time (PT), fibrinogen (FIB), and D-dimer on the overall survival (OS) of patients. Next, univariate analysis was utilized to identify prognostic factors, and a stepwise regression method was employed for variable selection to construct a nomogram based on the Cox proportional hazards model. Additionally, the predictive performance of the nomogram was assessed by the concordance index (C-index), the area under the ROC curve (AUC), and calibration curves. Finally, patients were stratified into risk groups based on the total score of the nomogram. The Kaplan–Meier survival curves indicated that immune-inflammatory scores NLR, PLR, SII, and coagulation indicators PT, FIB, and D-dimer were associated with OS. Through Cox regression analysis, a nomogram was ultimately constructed incorporating NLR, PLR, PT, alkaline phosphatase (ALP), carbohydrate antigen 125 (CA125), age, and ablation. The model demonstrated good discriminative ability, with a C-index of 0.722, and the AUC values at 6- and 12-month OS predictions were 0.828 and 0.851 in the training cohort, while in the validation cohort, the corresponding AUC values were 0.754 and 0.791, respectively. The calibration curves showed a good fit, confirming the stability of the model. A cutoff value of 353.3 was identified as optimal for risk stratification, with a statistically significant difference in OS between the high- and low-risk groups. The nomogram based on immune-inflammatory scores, coagulation indicators, and other clinicopathological factors can effectively predict the OS of patients with MPC.

Background: Transarterial chemoembolization (TACE) is recommended for intermediate-stage hepatocellular carcinoma (HCC). However, several therapies have shown better efficacy than TACE, meaning that the optimal therapy is unclear. We addressed this uncertainty using network meta-analysis (NMA).Methods: A literature review was performed up to March 15, 2024. Efficacy was evaluated using overall survival (OS) and progression-free survival (PFS). The hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from the Kaplan–Meier curves. A random-effects NMA was conducted, and subgroup analysis was performed according to the tumor number, tumor size, viral etiology, and alpha fetoprotein (AFP) level. The efficacy of the different therapies was ranked based on the P-score.Results: A total of 38 studies, 10,972 patients, and 13 therapeutic regimens were eligible. Seven therapies showed OS benefit over TACE, including TACE plus microwave ablation (MWA) (HR = 0.24, 95%CI = 0.06–0.91), TACE plus liver resection (HR = 0.35, 95%CI = 0.22–0.57), liver resection plus RFA (HR =0.49,95%CI=0.35-0.70), TACE plus immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) (HR = 0.51, 95%CI = 0.27–0.95), liver resection (HR = 0.54, 95%CI = 0.45–0.65), and TACE plus radiofrequency ablation (RFA) (HR = 0.57, 95%CI = 0.36–0.93). However, no therapies improved the PFS better than TACE alone. Subgroup analysis indicated that liver resection plus TACE showed the best OS for patients with hepatitis B virus (HBV) infection.Conclusions: Seven therapies showed better efficacy than TACE alone for particular patients with intermediate-stage HCC.Systematic review registration: https://www.crd.york.ac.uk/, PROSPERO CRD42023459740.