The advanced development of molecular targeted therapy for hepatocellular carcinoma

Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.

Response of cholangiocarcinoma with epigastric metastasis to lenvatinib plus sintilimab: A case report and review of literature

BACKGROUND Cholangiocarcinoma(CCA)poses a significant clinical challenge due to its low radical resection rate and a propensity for high postoperative recurrence,resulting in a poor dismal.Although the combination of targeted therapy and immunotherapy has demonstrated notable efficacy in several solid tumors recently,however,its application in CCA remains underexplored and poorly documented.CASE SUMMARY This case report describes a patient diagnosed with stage IV CCA,accompanied by liver and abdominal wall metastases,who underwent palliative surgery.Subsequently,the patient received two cycles of treatment combining lenvatinib with sintilimab,which resulted in a reduction in abdominal wall metastasis,while intrahepatic metastasis displayed progression.This unexpected observation illustrates different responses of intrahepatic and extrahepatic metastases to the same therapy.CONCLUSION Lenvatinib combined with sintilimab shows promise as a potential treatment strategy for advanced CCA.Genetic testing for related driver and/or passenger mutations,as well as an analysis of tumor immune microenvironment analysis,is crucial for optimizing drug combinations and eventually addressing the issue of non-response in specific metastatic sites.

Leveraging machine learning techniques for predicting pancreatic neuroendocrine tumor grades using biochemical and tumor markers

BACKGROUND The incidence of pancreatic neuroendocrine tumors (PNETs) is now increasing rapidly. The tumor grade of PNETs significantly affects the treatment strategy and prognosis. However, there is still no effective way to non-invasively classify PNET grades. Machine learning (ML) algorithms have shown potential in improving the prediction accuracy using comprehensive data. AIM To provide a ML approach to predict PNET tumor grade using clinical data. METHODS The clinical data of histologically confirmed PNET cases between 2012 and 2018 were collected. A method of minimum P for the Chi-square test was used to divide the continuous variables into binary variables. The continuous variables were transformed into binary variables according to the cutoff value, while the P value was minimum. Four classical supervised ML models, including logistic regression, support vector machine (SVM), linear discriminant analysis (LDA) and multi-layer perceptron (MLP) were trained by clinical data, and the models were labeled with the pathological tumor grade of each PNET patient. The performance of each model, including the weight of the different parameters, were evaluated. RESULTS In total, 91 PNET cases were included in this study, in which 32 were G1, 48 were G2 and 11 were G3. The results showed that there were significant differences among the clinical parameters of patients with different grades. Patients with higher grades tended to have higher values of total bilirubin, alpha fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 72-4. Among the models we used, LDA performed best in predicting the PNET tumor grade. Meanwhile, MLP had the highest recall rate for G3 cases. All of the models stabilized when the sample size was over 70 percent of the total, except for SVM. Different parameters varied in affecting the outcomes of the models. Overall, alanine transaminase, total bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 72-4 affected the outcome greater than other parameters. CONCLUSION ML could be a simple and effective method in non-invasively predicting PNET grades by using the routine data obtained from the results of biochemical and tumor markers.

Association of tumor morphology with long-term prognosis after liver resection for patients with a solitary huge hepatocellular carcinoma-a multicenter propensity score matching analysis

Background:A solitary hepatocellular carcinoma(HCC)without macrovascular invasion and distant metastasis,regardless of tumor size,is currently classified as early-stage disease by the latest Barcelona Clinic Liver Cancer(BCLC)staging system.While the preferred treatment is surgical resection,the association of tumor morphology with long-term survival outcomes after liver resection for a solitary huge HCC of≥10 cm has not been defined.Methods:Patients who underwent curative liver resection for a solitary huge HCC were identified from a multicenter database.Preoperative imaging findings were used to define spherical-or ellipsoidal-shaped lesions with smooth edges as balloon-shaped HCCs(BS-HCCs);out-of-shape lesions or lesions of any shape with matt edges were defined as non-balloon-shaped HCCs(NBS-HCCs).The two groups of patients with BS-HCCs and NBS-HCCs were matched in a 1:1 ratio using propensity score matching(PSM).Clinicopathologic characteristics,long-term overall survival(OS)and recurrence-free survival(RFS)were assessed.Results:Among patients with a solitary huge HCC,74 pairs of patients with BS-HCC and NBS-HCC were matched.Tumor pathological features including proportions of microvascular invasion,satellite nodules,and incomplete tumor encapsulation in the BS-HCC group were lower than the NBS-HCC group.At a median follow-up of 50.7 months,median OS and RFS of all patients with a solitary huge HCC after PSM were 27.8 and 10.1 months,respectively.The BS-HCC group had better median OS and RFS than the NBS-HCC group(31.9 vs.21.0 months,P=0.01;and 19.7 vs.6.4 months,P=0.015).Multivariate analyses identified BS-HCC as independently associated with better OS(HR=0.592,P=0.009)and RFS(HR=0.633,P=0.013).Conclusions:For a solitary huge HCC,preoperative imaging on tumor morphology was associated with prognosis following resection.In particular,patients with BS-HCCs had better long-term survival following liver resection versus patients with large NBS-HCCs.