Liver-related diseases, such as hepatocellular carcinoma (HCC) and cirrhosis, are globally prevalent and significantly contribute to mortality rates. Despite the availability of various imaging techniques for liver evaluation, a consensus regarding the selection of an accurate and safe method remains elusive. As a non-invasive imaging approach, the effectiveness of contrast-enhanced ultrasound (CEUS) in assisting the diagnosis and treatment of liver-related diseases has been established. Compared to conventional methods, CEUS offers notable advantages, including high safety, convenience, accuracy, and cost-effectiveness. Recent advancements have demonstrated the expanded utility of CEUS in liver-related diseases. In addition to diagnosing focal liver lesions, CEUS is increasingly employed for guiding local treatments, assessing liver transplantation suitability, and planning surgical interventions. However, its application requires caution due to the high technical proficiency demanded of operators, time-sensitive imaging processes, and susceptibility to visual interference. This review summarizes the current applications and recent advancements in CEUS-assisted diagnosis and treatment of liver-related diseases, explores its future potential, and proposes possible improvements. The objective is to enhance the accuracy and versatility of non-invasive liver assessments and provide a reference for the broader and more effective utilization of CEUS in liver disease diagnosis and management.

HER2 mutations have emerged as oncogenic driver gene mutations in non-small cell lung cancer (NSCLC), which have not been described in detail like other driver gene mutations. Here, 295 patients with advanced lung adenocarcinoma were retrospectively screened for HER2 mutations using next-generation sequencing (NGS), and the positive cases were validated by Sanger sequencing. We identified five cases with HER2 exon 20 insertions, representing 1.7% of 295 lung adenocarcinomas. Among them, four different subtypes of HER2 exon 20 insertions were identified, including a rare subtype G778_S779insCPG never reported before with a partial response (PR) to pyrotinib and progression-free survival (PFS) of 12.8 months. Our findings reveal that HER2 exon 20 insertion mutations were detected in a small subset of lung adenocarcinomas. Given the different drug sensitivities, determining the mutation subtype by next-generation sequencing at the time of diagnosis might make sense.

Pooled analysis of the SPOTLIGHT and GLOW phase III trials, involving 1072 patients with locally advanced or metastatic gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma positive for claudin18.2 (CLDN18.2) and negative for HER2, showed that zolbetuximab combined with chemotherapy significantly improved progression-free survival (PFS) compared to placebo (HR = 0.72; 95% CI, 0.61–0.84). Subgroup analyses revealed better outcomes in Asian patients, those with gastric cancer, and those with intestinal-type GC. In a cohort of 92 GC patients (immunohistochemical detection based on a CLDN18.2 subtype-specific antibody), CLDN18.2 positivity was associated with lymph node metastasis, advanced cancer stages (III–IV), and shorter overall survival (OS) (HR = 1.728; 95% CI, 1.003–2.977; P = 0.0404). In our study, knockdown of CLDN18.2 inhibited tumor growth in vivo and in vitro. Additionally, CLDN18.2 knockdown down-regulated minichromosome maintenance (MCM) proteins, particularly MCM2 and MCM5, and decreased phosphorylation of ERK, CDK, and MCM2 in GC cells. These findings provide a theoretical basis for the future selection of advantageous populations for CLDN18.2-targeted therapy and combination therapy strategies.

Colorectal cancer is a malignant disease with high morbidity and mortality. In recent years, immune checkpoint inhibitors have emerged as a promising therapeutic strategy; however, patients with proficient mismatch repair/microsatellite-stable (pMMR/MSS) colorectal cancer derive limited benefit from immunotherapy. We conducted a single-arm, exploratory clinical study to evaluate the efficacy of camrelizumab combined with apatinib in patients with advanced metastatic colorectal cancer who had received third-line or later treatment. This trial is registered with ClinicalTrials.gov (NCT04067986; registered August 20, 2019). Our results demonstrated that apatinib significantly enhanced the therapeutic efficacy of immunotherapy in patients with pMMR/MSS colorectal cancer. Mechanistically, apatinib improved immunotherapy outcomes by modulating the tumor microenvironment in vivo. Further in vitro experiments revealed that apatinib reduced levels of exosomal PD-L1 in the tumor microenvironment by inhibiting tumor-derived exosome secretion. This inhibitory effect was mediated through the regulation of Exo70. Collectively, our findings indicate that apatinib enhances the efficacy of camrelizumab in pMMR/MSS colorectal cancer and provide a theoretical rationale for the combined use of camrelizumab and apatinib in this patient population.