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Immune checkpoint inhibitors (ICIs) like programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor have shown considerable efficacy in several important cancers including primary liver cancer (PLC) like hepatocellular carcinoma and cholangiocarcinoma. However, only some patients with PLC will benefit, so combination therapy and biomarker classification detected by next-generation sequencing or immunohistochemistry are very important. Herein, we briefly summarize ICI-based therapies and stratify these evolving therapies for advanced PLC into three stages of immunotherapies Mark (Mk.) 1.0, 2.0, and 3.0. We illustrated the significance of ICI monotherapy (Mk. 1.0), offering combinational approaches with traditional strategies (Mk. 2.0) and additional locoregional therapy (Mk. 3.0) to achieve longer survival and even meet the “No Evidence of Disease” status. We also highlight the importance of biomarkers and prognostic factors for patients with advanced PLC treated with ICI-based therapies. Multidisciplinary team management should be investigated and collaborated closely to manage adverse events and sequential therapy suggestions for patients.

Since the publication of the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2019 Edition), many new high-level evidence in line with evidence-based medicine has emerged in the diagnosis and treatment of liver cancer at home and abroad, especially, a number of research results in line with Chinese liver cancer patients have been published. In order to further standardize the diagnosis and treatment of liver cancer in China, the National Health Commission organized multidisciplinary experts in the field of liver cancer to revise and update the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition), aiming to increase the overall cancer 5-year survival rate by 15%, a goal mentioned in the ' Healthy China 2030' Planning Outline. We interpret the main update points of the 2022 version, with the hope of promoting the widespread discussion and dissemination of the new version.

Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient‐derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d‐bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient‐derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient‐derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM. [ABSTRACT FROM AUTHOR]

Background: Therapeutic approaches for extrahepatic cholangiocarcinoma (EHCC) are limited, due to insufficient understanding to biomarkers related to prognosis and drug response. Here, we comprehensively assess the molecular characterization of EHCC with clinical implications. Methods: Whole‐exome sequencing (WES) on 37 tissue samples of EHCC were performed to evaluate genomic alterations, tumor mutational burden (TMB) and microsatellite instability (MSI). Results: Mutation of KRAS (16%) was significantly correlated to poor OS. ERBB2 mutation was associated with improved OS. ERBB2, KRAS, and ARID1A were three potentially actionable targets. TMB ≥10 mutations per megabase was detected in 13 (35.1%) cases. Six patients (16.2%) with MSIsensor scores ≥10 were found. In multivariate Cox analysis, patients with MSIsensor sore exceed a certain threshold (MSIsensor score ≥0.36, value approximately above the 20th percentile as thresholds) showed a significant association with the improved OS (HR = 0.16; 95% CI: 0.056–0.46, p < 0.001), as well as patients with both TMB ≥3.47 mutations per megabase (value approximately above the 20th percentile) and MSIsensor score ≥0.36. Conclusions: TMB and MSI are potential biomarkers associated with better prognosis for EHCC patients. Furthermore, our study highlights important genetic alteration and potential therapeutic targets in EHCC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most predominant primary liver cancer, causing many illnesses and deaths worldwide. The insidious clinical presentation, difficulty in early diagnosis, and the highly malignant nature make the prognosis of HCC extremely poor. The complex and heterogeneous pathogenesis of HCC poses significant challenges to developing therapies. Urine-based biomarkers for HCC, including diagnostic, prognostic, and monitoring markers, may be valuable supplements to current tools such as serum α-fetoprotein (AFP) and seem promising for progress in precision medicine. Herein, we reviewed the major urinary biomarkers for HCC and assessed their potential for clinical application. Molecular types, testing platforms, and methods for building multimolecule models in the included studies have shown great diversity, thus providing abundant novel tools for future clinical transformation and applications. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the effects of intermittent bolus paravertebral block on analgesia and recovery in open hepatectomy. Methods: Eighty 18–70 years old, American Society of Anesthesiologists level I-III patients scheduled for hepatectomy with a J-shaped subcostal incision were enrolled and randomized to receive either intermittent bolus paravertebral ropivacaine (0.5% loading, 0.2% infusion) or 0.9% saline infusion at 1:1 ratio (25 ml loading before surgery, 0.125 ml/kg/h bolus for postoperative 48 h). The primary outcome was set as postoperative 48 h cumulative intravenous morphine consumption recorded by a patient-controlled analgesic pump. Results: Thirty-eight patients in each group completed the study. The cumulative morphine consumptions were lower in the paravertebral block than control group at postoperative 24 (difference -10.5 mg, 95%CI -16 mg to -6 mg, P < 0.001) and 48 (difference -12 mg, 95%CI -19.5 mg to -5 mg, P = 0.001) hours. The pain numerical rating scales at rest were lower in the paravertebral block than control group at postoperative 4 h (difference -2, 95%CI -3 to -1, P < 0.001). The active pain numerical rating scales were lower in the paravertebral block than control group at postoperative 12 h (difference -1, 95%CI -2 to 0, P = 0.005). Three months postoperatively, the paravertebral block group had lower rates of hypoesthesia (OR 0.28, 95%CI 0.11 to 0.75, P = 0.009) and numbness (OR 0.26, 95%CI 0.07 to 0.88, P = 0.024) than the control group. Conclusions: Intermittent bolus paravertebral block provided an opioid-sparing effect and enhanced recovery both in hospital and after discharge in patients undergoing hepatectomy. Trial registration: clinicaltrials.gov (NCT04304274), date: 11/03/2020. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Byline: Bao. Jin, Shunda. Du, Haifeng. Xu, Yongchang. Zheng, Xin. Lu, Xinting. Sang, Yilei. Mao Background: Laparoscopic hepatectomy is more conducive to the rapid rehabilitation of patients after surgery compared [...]

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. [ABSTRACT FROM AUTHOR]

Purpose: To quantitatively analyze lipid molecules in tumors and adjacent tissues of intrahepatic cholangiocarcinoma (ICC), to establish diagnostic model and to examine lipid changes with clinical classification. Patients and Methods: We measured the quantity of 202 lipid molecules in 100 tumor observation points and 100 adjacent observation points of patients who were diagnosed with ICC. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were handles, along with Student's t-test to identify specific metabolites. Prediction accuracy was validated in the validation set. Another logistic regression model was also established on the training set and validated on the validation set. Results: Distinct separation was obtained from PCA and OPLS-DA model. Ten differentiating metabolites were identified using PCA, OPLA-DA and Lasso regression: [m/z 722.5130], [m/z 863.5655], [m/z 436.2834], [m/z 474.2626], [m/z 661.4813], [m/z 750.5443], [m/z 571.2889], [m/z 836.5420], [m/z 772.5862] and [m/z 478.2939]. Using logical regression, a diagnostic equation: y = 3.4*[m/z 436.2834] - 3.773*[m/z 474.2626] + 3.82*[m/z 661.4813] - 4.394*[m/z 863.5655] + 10.165 based on four metabolites successfully differentiated cancerous areas from adjacent normal areas. The AUROC of the model reached 0.993 (95% CI: 0.985– 0.999) in the validation group. Compared with the adjacent non-tumor area, three characteristic metabolites FA (22:4), PA (P-18:0/0:0) and Glucosylceramide (d18:1/12:0) showed an increasing trend from stage I to stage II, while seven other metabolites LPA(16:0), PE(34:2), PE(36:4), PE(38:3), PE(40:6), PE(40:5) and LPE(16:0) showed a decreasing trend from stage I to stage II. Conclusion: We successfully identified lipid molecules in differentiating tumor tissue and adjacent tissue of ICC, established a discrimination logistic model which could be used as a classifier to classify tumor and non-tumor regions based on analysis in tumor margins and provided information for biomarker changes in ICC, and proposed to related lipid changes with clinical classification. [ABSTRACT FROM AUTHOR]