Introduction

Esophageal Squamous Cell Carcinoma (ESCC) remains a significant global health problem with few therapeutic options and poor prognosis. Camrelizumab, an anti-PD-1 immune checkpoint inhibitor, has been shown in clinical trials to be of potential value in the treatment of advanced or metastatic ESCC as monotherapy or in combination with chemotherapy or anti-angiogenic therapy.

Aims & Methods

The aim of this study is to evaluate the clinical efficacy and safety profile of Camrelizumab in patients with esophageal squamous cell carcinoma, with the main outcomes being progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events.
We conducted a comprehensive search of PubMed, Scopus, Web of Science, Embase, and Cochrane from their inception to April 2025, focusing on randomized controlled trials (RCTs) and observational studies evaluating Camrelizumab for the treatment of esophageal squamous cell carcinoma. Meta-analyses utilized a random-effects model to calculate odds ratios, mean differences, and 95% confidence intervals for adverse events and total patients.

Results

Out of 1,563 studies initially screened, 15 studies met the inclusion criteria for our meta-analysis, comprising adult patients. Meta-analysis established a median progression-free survival (PFS) of 7.60 months (95% CI: 6.00–9.19). The major pathological response rate (MPR) was 0.42 (95% CI: 0.37–0.48), and the objective response rate (ORR) was 0.53 (95% CI: 0.38–0.68). The R0 resection rate was also remarkably high at 0.98 (95% CI: 0.96–1), and the disease control rate (DCR) was 0.87 (95% CI: 0.64–1). The pathological complete response rate (pCR) was 0.31 (95% CI: 0.20–0.43).
Regarding safety, the most common treatment-related adverse events were leukopenia 0.45 (95% CI: 0.23–0.68), neutropenia 0.30 (95% CI: 0.19–0.41), anemia 0.14 (95% CI: 0.03–0.29), thrombocytopenia 0.09 (95% CI: 0.03–0.17), and elevated transaminases 0.06 (95% CI: 0.02–0.12). Pneumonia 0.17 (95% CI: 0.11-0.23) and hypertension 0.12 (95% CI: 0.06-0.19) were the other immune-related adverse events. The majority of these events were tolerable and within safe parameters.

Conclusion

Camrelizumab demonstrates promising efficacy in the treatment of esophageal squamous cell carcinoma with satisfactory rates of ORR, MPR, and R0 resection. The safety profile is acceptable with controllable adverse effects. These findings support the potential therapeutic value of camrelizumab as a significant treatment strategy in multimodal treatment of esophageal squamous cell carcinoma and the need for further research to optimize its clinical use.

Introduction

Acetaminophen (APAP) is a major cause of drug-induced liver injury (DILI), once the latter evolves into liver failure, it significantly impacting clinical outcomes. Urokinase plasminogen activator receptor (uPAR) is a membrane protein that is distributed on various immune-active cell membranes, which is not only associated with cell adhesion, invasion and migration, but also can regulate the immune microenvironment. However, uPAR specific roles in the regulation of myeloid cell innate immunity and the maintenance of hepatic homeostasis during DILI remains unclear.

Aims & Methods

The expression pattern of uPAR in both mouse DILI models and DILI patients was determined. Multiplex Immunohistochemistry (mIHC), flow cytometry, spatial transcriptomics (ST), single-cell RNA sequencing (scRNA-seq), intravital 3D imaging, luciferase reporter gene assay and Cleavage Under Targets and Tagmentation (CUT&Tag) were used to explore molecular mechanisms. uPAR^-/-, Lyz2^creuPAR^f/f and AXL^-/- mice, various mouse primary cells, human liver and serum samples were used to verify the discoveries of bioinformatics analysis.

Results

We found that the expression level of uPAR in the liver of both mouse DILI models and DILI patients was significantly high, systemic and myeloid deficiency of uPAR could alleviate liver inflammation in mice after challenged with APAP. mIHC, flow cytometry, ST, scRNA-seq and intravital 3D imaging multidimensionally elucidated that macrophage efferocytosis in both uPAR^-/- and Lyz2^creuPAR^f/f mice was enhanced due to the upregulation of the AXL, leading to the accelerated clearance of senescent neutrophils and thereby promoting the resolution of liver inflammation. Luciferase reporter gene assay and CUT&Tag confirmed that transcription factor IRF7 directly bound to the promoter region of AXL in macrophages. Mechanistic studies showed that uPAR regulated AXL mediated efferocytosis through the STAT3/IRF7 pathway. Macrophage-specific overexpression of IRF7 in vivo enhanced macrophage efferocytosis and promoted the attenuation of liver inflammatory response in both mouse DILI and liver ischemia-reperfusion injury models. AXL^-/- mice had exacerbated phenotype, while AXL activator GAS-6 protein could alleviate liver injury.

Conclusion

uPAR/STAT3/IRF7/AXL signaling is critical to regulate macrophage efferocytosis and maintain hepatic tissue homeostasis in the progression of DILI. Its dual functionality as a liver homeostatic regulator and DILI therapeutic target warrants further investigation.

Introduction

Post-liver transplant (LT) bile leaks (BLs) are successfully treated by endoscopic retrograde cholangiopancreatography (ERCP). While fully covered self-expandable metal stents (fc-SEMSs) have shown promising results, their use is often limited by concerns regarding adverse events (AEs), with limited data comparing their efficacy and safety. Moreover, European guidelines do not clearly endorse their up-front use over plastic stents. To date, no studies have directly compared these two treatments for post-LT BLs.

Aims & Methods

This study aims to compare the safety and efficacy of plastic versus fc-SEMS in treating post-LT BLs.
We conducted a retrospective study in single tertiary endoscopy center, reviewing cases from January 2018 to March 2024. Among 223 ERCPs performed in LT recipients, 30 patients treated with ERCP as first-line therapy for post-LT BLs were included. Patients with biliodigestive anastomosis dehiscence or prior interventions (percutaneous drainage or surgery) were excluded.

Results

Of the 30 patients (96.7% duct-to-duct anastomosis), 14 (46.7%) received plastic stents and 16 (53.3%) received fc-SEMSs. Anastomotic leaks were the predominant type (85.7% in the plastic stent group vs. 87.5% in the fc-SEMS group).Both groups achieved 100% technical and clinical success. No significant differences in AE rates were observed (42.9% for plastic vs. 37.5% for fc-SEMS, p=0.1), and no severe complications occurred. Among the 13 patients in whom biliary strictures (BSs) were reported, 4 cases were de novo strictures, occurring equally in the plastic stent group (n=2) and the fc-SEMS group (n=2). The remaining 9 strictures were present prior to BL treatment (3 in the plastic stent group and 6 in the fc-SEMS group). Resolution of BSs was achieved in 66.7% (4/6) of patients treated with fc-SEMSs, compared to 33.3% (1/3) in the plastic stent group, showing a borderline statistically significant difference (p=0.05), though this was limited by the small sample size. No patient required rescue procedures for persistent BL. A median of 2 ERCP sessions per patient (SD ±1) was needed for complete BL resolution. During a median follow-up of 8 months (IQR 1–27.3), only one recurrence occurred in the plastic stent group, successfully managed with fc-SEMS.

Conclusion

ERCP with either plastic stents or fc-SEMSs effectively treats post-LT BLs, with no significant differences in AEs between the two groups. Given their comparable success and safety, fc-SEMS could be considered not only as a rescue therapy but also as a primary, effective and safe treatment option.

References

1. Moy BT, Birk JW. A Review on the Management of Biliary Complications after Orthotopic Liver Transplantation. J Clin Transl Hepatol. 2019;7(1):61-71
2. Phillips MS, Bonatti H, Sauer BG, et al. Elevated stricture rate following the use of fully covered self-expandable metal biliary stents for biliary leaks following liver transplantation. Endoscopy. 2011;43(6):512-517
3. Dumonceau JM, Kapral C, Aabakken L, et al. ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2020;52(02):127-149