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Background The dismal prognosis of hepatocellular carcinoma (HCC) is closely associated with characteristics of the tumour microenvironment (TME). Recent studies have confirmed the presence and potential influence of the microbiome in TME on cancer progression. Elucidating the relationship between microbes in the TME and cancer could provide valuable insights into novel diagnostic markers and therapeutic strategies for HCC and thus warrants a closer investigation of the role of intratumoural microbiome in the HCC TME. Methods We determined the presence of intratumoural microbiome using fluorescence in situ hybridisation, and explored the microbial community profiles in the HCC TME in paired tumour and adjacent normal tissues using 16S rDNA sequencing. Microbial signatures were characterised in the paired group, and their correlation with clinical characteristics was further investigated. We clustered the microbial signatures of tumour tissues by hepatotypes, and further analysis was performed to elucidate the independent prognostic value of the hepatotypes. Results This study revealed that microbial profiles and community networks differed notably between tumours and adjacent normal tissues. Proteobacteria and Actinobacteria were the most abundant phyla in the HCC TME. The TME microbial profiles also revealed heterogeneities between individuals and between multiple tumour lesions. Clustering of the microbial profiles into two hepatotypes revealed different microbial network patterns. Additionally, the hepatotypes were revealed to be independent prognostic factors in patients with resected HCC. Conclusions Our study illuminates the microbial profiles in the TME of HCC and presents the hepatotype as a potential independent biomarker for the prognostic prediction of HCC after surgery.

Immunologic checkpoint inhibitors (ICIs) have demonstrated efficacy in a variety of malignancies. Despite impressive therapeutic benefits, ICIs may induce profound immune-related adverse events (irAEs). While the occurrence of irAEs may implicate improved T cell activity, whether irAEs predicts anti-tumor immune responses remains controversial. The paper by Kennedy Yao Yi Ng et al. adds to the evidence of the impact of irAEs in advanced hepatocellular carcinoma, which demonstrated that multi-system involvement of irAEs positively correlated with treatment responses and survival. We are, however, concerned about the grouping method and potential statistical bias. Therefore, we listed a few questions and possible solutions under each circumstance, which we would like to share with authors and readers.

Background: Short-term outcomes of laparoscopic hepatectomy of central-located liver lesions (LHCL) compared with traditional open hepatectomy of central-located liver lesions (OHCL) remain unclear. The aim of this study was to explore the safety and efficacy of LHCL. Methods: A retrospective analysis was performed on 262 patients who underwent hepatectomies involving resections of liver segment II, IV or VIII from January 2015 to June 2021 in two institutions. Patients in the LHCL group were matched in a 1:2 ratio to patients in the OHCL group. Results: After propensity score-matched (PSM) analysis, 61 patients remained in the LHCL group and 122 patients were in the OHCL group. What needs to be mentioned is that although not significant, patients in the OHCL group had increased lesion size (4.3 vs. 3.6 cm, p = 0.052), number (single/multiple, 84.8%/15.2% vs. 93.4%/6.6%, p = 0.097), and number of liver segments involved (one/two/three, 47.3%/42.0%/10.7% vs. 57.4%36.1%/10.7%, p = 0.393). To ensure surgical safety, fewer patients in the LHCL group underwent vascular exclusion than those in the OHCL group (p = 0.004). In addition, LHCL was associated with lower blood loss (p = 0.001) and transfusion requirement (p = 0.004). In terms of short-term outcomes, the LHCL group had significantly lower levels of peak ALT (p < 0.001), peak DBIL (p = 0.042), peak PT (p = 0.012), and higher levels of bottom ALB (p = 0.049). Moreover, the LHCL group demonstrated quicker postoperative recovery, which was represented by shorter time to first flatus, time to oral intake, time to drain off, and hospital stay (all p < 0.001). Importantly, the LHCL group had a significantly reduced occurrence of postoperative complications (p < 0.001) and similar R0 resection rates (p = 0.678) when compared to the OHCL group. Conclusion: LHCL is associated with increased safety and better perioperative outcomes and thus could be recommended for patients with central space-occupying liver lesions when appropriately selecting the surgical procedure according to the total tumor burden and carefully handled by experienced surgeons. From the experience of our center, LHCL could be performed to solitary lesion involving liver segment IV/V/VIII, <5 cm, with good safety and feasibility.