Safety and long-term prognosis of simultaneous versus staged resection in synchronous colorectal cancer with liver metastasis: a systematic review and meta-analysis.

PURPOSE: The optimal time point for surgical resection of synchronous colorectal liver metastases (SCLMs) is still controversial. This meta-analysis evaluated the safety and long-term prognoses of simultaneous and staged resection of SCLM to provide a reference for clinical selection. METHODS: A systematic literature search for studies published by October 2022 was performed using PubMed, Web of Science, Embase, Scopus and Cochrane Library. The evaluated outcome parameters were total, gastrointestinal and hepatic complications, as well as perioperative mortality, intraoperative blood loss, total hospital stay, 5-year disease-free survival (DFS) and 5-year overall survival (OS). RESULTS: This meta-analysis included 22 nonrandomised and one randomised study comprising 4862 patients. The patients undergoing simultaneous resection of SCLM had similar total (OR = 0.88, 95% CI [0.66-1.19], P = 0.409), gastrointestinal (OR = 1.19, 95% CI [0.89-1.59], P = 0.241) and hepatic (OR = 1.04, 95% CI [0.83-1.31], P = 0.734) complications, as well as perioperative mortality (OR = 1.79, 95% CI [0.88-3.64], P = 0.108), 5-year DFS (HR = 1.26, 95% CI [0.96-1.66], P = 0.098) and 5-year OS (HR = 1.13, 95% CI [0.95-1.34], P = 0.164). Lower intraoperative blood loss (SMD = - 0.39, 95% CI [- 0.60 to - 0.18], P < 0.001) and shorter total hospital stay (WMD = - 5.43, 95% CI [- 7.29 to - 3.58], P < 0.001) were observed in the simultaneous-resection group versus the staged group. CONCLUSIONS: Simultaneous resection is safe and effective for SCLM patients. The long-term prognosis is equivalent to that of the traditional staged resection. Correct selection of resectable SCLM patients for the simultaneous resection of the primary tumour and liver metastases can be the first choice. Owing to the potential heterogeneity, more RCTs should be included to verify our conclusions.

Super-enhancer-driven AJUBA is activated by TCF4 and involved in epithelial-mesenchymal transition in the progression of Hepatocellular Carcinoma.

Background and Aims: Aberrant transcriptional programs are highly regulated processes that play important roles in the development and progression of hepatocellular carcinoma (HCC). Emerging evidence suggests that super-enhancers (SEs) often drive critical oncogene expression. However, SE-associated genes in HCC pathogenesis are still poorly understood. Methods: We performed integrative ChIP-seq and Hi-C analyses of HCC cells and identified ajuba LIM protein (AJUBA) as a SE-associated gene. We evaluated AJUBA expression in HCC using immunohistochemistry, immunoblotting, and qRT-PCR. ChIP and luciferase reporter assays were performed to demonstrate that transcription factor 4 (TCF4) bound to AJUBA-associated SEs. We then assessed the role of AJUBA in HCC using both in vitro and in vivo assays. Epithelial-mesenchymal transition (EMT) was examined using immunofluorescence and immunoblotting assays. Furthermore, we used immunoprecipitation and BiFC assays to explore the underlying mechanisms. Results: We identified AJUBA as a SE-associated oncogene in HCC regulated by TCF4. High AJUBA expression was related to an aggressive phenotype and unfavorable outcome in HCC patients. AJUBA knockdown significantly reduced cell migration and invasion capacities both in vitro and in vivo. Furthermore, AJUBA overexpression in HCC recruited tumor necrosis factor associated factor 6 (TRAF6), enhancing the phosphorylation of Akt and increasing Akt activity toward GSK-3ß, thus promoting EMT. Conclusions: Our results provide functional and mechanistic links between the SE-associated gene AJUBA and tumor EMT in aggressive HCC.

Programmed death-ligand 1 expression correlates with diminished CD8+ T cell infiltration and predicts poor prognosis in anal squamous cell carcinoma patients.

OBJECTIVE: Increased expression of programmed death-ligand 1 (PD-L1) on tumor cells can be found in various malignancies; however, very limited information is known about its role in anal squamous cell carcinoma (ASCC). This study explored PD-L1 expression in ASCC patients and its association with patients' clinicopathological features, CD8+ T cell infiltration, and prognosis. METHODS: Formalin-fixed paraffin-embedded tumor samples from 26 patients with ASCC were retrieved. The levels of PD-L1 expression on the membrane of both tumor cells and tumor-infiltrating mononuclear cells (TIMCs) were evaluated by immunohistochemistry. CD8+ T cell densities, both within tumors and at the tumor-stromal interface, were also analyzed. Baseline clinicopathological characteristics, human papilloma virus (HPV) status, and outcome data correlated with PD-L1-positive staining. RESULTS: PD-L1 expression on tumor cells and TIMCs was observed in 46% and 50% of patients, respectively. Nineteen patients (73%) were HPV positive, with 7 showing PD-L1-positive staining on tumor cells and 9 showing PD-L1-positive staining on TIMCs. Increasing CD8+ density within tumors, but not immune stroma, was significantly associated with decreased PD-L1 expression by both tumor cells and TIMCs (P=0.0043 and P=0.0007). Patients with negative PD-L1 expression had significantly better progression-free survival (P=0.038 and P=0.0443) and a non-statistically significant trend toward longer overall survival (P=0.0882 and P=0.1222) compared with patients with positive PD-L1 expression. CONCLUSION: PD-L1 is widely expressed on the membrane of tumor cells and TIMCs in ASCCs. Its negative impact on prognosis may be due to the diminished CD8+ T cell infiltration within tumors.