Background: The presence of microvascular invasion (MVI) is a significant malignant pathological feature related to recurrence and survival after liver resection for hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the severity in the grading of MVI and long-term oncological outcomes in patients with early-stage HCC. Methods: A retrospective study was conducted on a prospectively maintained multicenter database on patients who underwent curative resection for Barcelona Clinic Liver Cancer stage 0/A HCC between 2017 and 2020. Patients were classified into three groups according to the severity in the grading of MVI: M0 (no MVI), M1 (1–5 sites of MVI occurring ≤1 cm away from the tumor), and M2 (>5 sites occurring ≤1 cm and/or any site occurring >1 cm away from the tumor). Recurrence-free survival (RFS) and overall survival (OS) were compared among the groups. Results: Of 388 patients, M0, M1, and M2 of the MVI gradings were present in 223 (57.5%), 118 (30.4%), and 47 (12.1%) patients, respectively. The median OS and RFS in patients with M0, M1, and M2 were 61.1, 52.7, and 27.4 months; and 43.0, 29.1, and 13.1 months (both P<0.001), respectively. Multivariable analyses identified both M1 and M2 to be independent risk factors for OS [hazard ratio (HR): 1.682, P=0.003; and HR: 3.570, P<0.001] and RFS (HR: 1.550, P=0.037; and HR: 2.256, P<0.001). Conclusion: The severity in the grading of MVI was independently associated with recurrence and survival after HCC resection. Patients with the presence of MVI, especially those with a more severe MVI grading (M2), require more stringent recurrence surveillance and/or active adjuvant therapy against recurrence.

Objectives: Hepatocellular carcinoma (HCC) is a common indication for hepatectomy that is often complicated by postoperative complication. The authors sought to investigate the relationship between the open with laparoscopic approach of hepatectomy and incidences of postoperative infectious complications. Patients and methods: Using a multicenter database, HCC patients who underwent laparoscopic hepatectomy (LH) or open hepatectomy (OH) were reviewed and analyzed. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and multivariate logistic regression analyses were utilized to assess the association of the operative approach with postoperative infectious complications, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI). Results: Among 3876 patients, 845 (21.8%) and 3031 (78.2%) patients underwent LH and OH, respectively. The overall incidence of infection was 6.9 versus 14.6% among patients who underwent LH versus OH, respectively (P<0.001). Of note, the incidences of incisional SSI (1.8 vs. 6.3%, P<0.001), organ/space SSI (1.8 vs. 4.6%, P<0.001), and RI (3.8 vs. 9.8%, P<0.001) were all significantly lower among patients who underwent LH versus OH. After PSM (6.9, 1.8, 1.8, and 3.8% vs. 18.5, 8.4, 5.2, and 12.8%, respectively) and IPTW (9.5, 2.3, 2.1, and 5.5% vs. 14.3, 6.3, 4.5, and 9.8%, respectively), LH remained associated with statistically lower incidences of all types of infectious complications. After adjustment for other confounding factors on multivariate analyses, LH remained independently associated with lower incidences of overall infection, incisional SSI, organ/space SSI, and RI in the overall, PSM, and IPTW cohorts, respectively. Conclusion: Compared with open approach, laparoscopic approach was independently associated with lower incidences of postoperative infectious complications following hepatectomy for HCC.

Background and Aims: Intrahepatic cholangiocarcinoma (ICC) is characterized by high malignancy, and its global incidence is predicted to continue to increase over the past decades. However, the mechanisms underlying ICC pathogenesis and progression remain unclear. Approach and Results: The training cohort consisted of single-cell sequencing of 12 treatment-naïve ICC samples and spatial transcriptomics of four ICC samples. The validation cohort comprised of RNA-seq data from 87 ICC tumor samples. Finally, we validated our findings via multiplex immunofluorescence, organoids, and mice models both in vivo and in vitro. We found significant heterogeneity within the tumor microenvironment (TME) of ICC patients. ICC cells were classified into five molecular subtypes, and we revealed that aspartate beta-hydroxylase (ASPH) was a marker gene for invasion subtypes. We then selected cepharanthine (CEP) as an ASPH inhibitor that effectively suppressed tumor progression. Regarding the ICC lymphatic metastasis mechanism, we found that tumor cells in N1 lymph nodes highly expressed tumor-specific MHC-II molecules but lacked co-stimulatory factors CD80/CD86, inducing a state of anergy in CD4+ T cells, which might facilitate ICC immune evasion. Conclusions: The TME of ICC was heterogeneous. ASPH markedly enhanced ICC invasion The ASPH inhibitor CEP significantly inhibits ICC progression and may serve as a targeted therapeutic drug for ICC. Tumor cells in N1 lymph nodes demonstrate high expression of tumor-specific MHC-II molecules, but silencing of co-stimulatory factors such as CD80/CD86 induces CD4+ T cells into an anergic state. Our study indicated that ASPH and MHC-II may serve as novel therapeutic targets for ICC. Export

Hepatocellular carcinoma (HCC) is a prevalent malignancy with poor prognosis. This study uses integrated bioinformatic analyses to explore potential competing endogenous RNA (ceRNA) network chains in HCC. HCC expression profile data were obtained from the Gene Expression Omnibus dataset, and differential expression analysis was conducted to identify differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs), and long non-coding RNAs (DElncRNAs) between HCC and normal liver tissue samples. Univariate Cox regression analysis was performed to identify mRNAs associated with the prognosis of HCC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to classify the identified genes functionally. Cytoscape software was used to construct a protein–protein interaction network. Using the intersection method, a ceRNA network was established to align data from two databases (miRTarBase and miRcode). Pearson correlation analysis was conducted to evaluate the relationships between lncRNAs and mRNAs. A total of 106 prognosis-related DEmRNAs were identified between HCC and normal samples. A total of 132 DEmiRNAs and 42 DElncRNAs were dysregulated in HCC. A ceRNA network of three lncRNAs, six miRNAs, and eight mRNAs was constructed. High expression of MCM10, CDKN3, RRM2, KIF3A, and ALYREF correlated with a poor prognosis, while high expression of CPEB2, COLEC10, and PBLD was associated with a better prognosis for HCC patients. Expression analysis confirmed the differential expression of these genes in HCC samples. Correlation analysis revealed that a MAGI2-AS3/hsa-miR-450b-5p/COLEC10 axis might play a crucial role in the progression of HCC. The ceRNA network constructed could provide insight into HCC tumorigenesis and might lead to new molecular biomarkers for diagnosing and treating HCC.