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Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4,2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.
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The pandemic of Corona Virus Disease 2019 (COVID-19) continues, which shows the concentrated or sporadic cases in multiple places. Current COVID situation is still complex. During the COVID-19, routine diagnosis and treatment of liver cancer patients has been affected in different degrees. Under the premise of following the treatment guidelines, how to reduce the risk of infection of patients and medical staff, utilize limited medical resources to maximally ensure anti-tumor treatment and related emergency treatment, and help patients get through the epidemic period is a problem for liver oncologists. Thus, experts of liver cancer treatment related disciplines of Zhongshan Hospital, Fudan University have written the Expert guidance on overall management of liver cancer during the COVID-19, which aims to provide references for liver oncolo-gists to conduct clinical work safely and effectively under the epidemic prevention and control, and to help patients fight against the epidemic smoothly.
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Tumor recurrence and metastasis after liver transplantation (LT) remains one of the most important factors that affect the outcome of LT for hepatocellular carcinoma (HCC). The diagnosis and treatment strategies in the era of precision medicine, including utilizing multi-omics, high-throughput gene sequencing analysis, big data and artificial intelligence to select the biomarkers which can accurately predict the prognosis after LT, evaluating the immune status comprehensively, inducing immune tolerance, providing effective prevention for patients at a high risk of recurrence with sensitive antitumor drugs and attaching importance to individualized treatment for recurrence and metastasis, may further improve the outcome of LT. Combined with experience and review of relevant research articles, the authors elaborate perioperative diagnosis and treatment strategies of LT for HCC, aiming to promote the application of precision medicine in the field of LT.
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Objective:To investigate the expression of four cancer stem cell (CSC) markers (EpCAM, CD133, CD90 and CD24) in hepatocellular carcinoma tissues and peripheral blood circulating tumor cells (CTC),their value in the prognosis of patients with hepatocellular carcinoma.Methods:A total of 50 hepatocellular carcinoma tissues and 29 peripheral blood sample from 50 patients with hepatocellular cancer treated in Zhongshan Hospital Fudan University from October 2013 to September 2014 were collected and analyzed by flow cytometry or qRT-PCR to examine the expression of EpCAM, CD133, CD90 and CD24. The clinical data of patients were collected, including tumor size, tumor number, satellite lesions, vascular invasion, Edmondson stage, BCLC stage and liver cirrhosis, etc. The correlation between the expression of four markers in hepatocellular carcinoma tissues and CTC with the clinical data and survival time of patients were compared.Results:The positive expression rates of EpCAM, CD133, CD90 and CD24 in hepatocellular carcinoma tissues were 66% (33/50), 18% (9/50), 60% (30/50) and 56% (28/50); the positive expression rates in CTC were 55% (16/29), 38% (11/29), 31% (9/29) and 59% (17/29). CD90 expression in hepatocellular carcinoma tissue was positively correlated with the occurrence HCC liver cirrhosis ( P<0.05), while CD133 expression was negatively correlated with the 5-year survival rate of patients ( P<0.05). The expression of EpCAM and CD24 in peripheral blood CTC were closely related to the patient′s Edmondson stage ( P<0.05). The survival time of patients with CD133 positive expression in hepatocellular carcinoma tissue was lower than those without CD133 expression ( P<0.05); the survival rate of patients with EpCAM expressed in either tissue or peripheral blood CTC was lower than that of patients with EpCAM double negative expression ( P<0.05). The survival rate of patients with CD90 negative in HCC tissue and positive in peripheral blood was lower than that in patients with double negative/double positive in tissue and peripheral blood or patients positive in hepatocellular carcinoma tissue and negative in peripheral blood ( P<0.01). Conclusion:Different expression characteristics of four markers in cancer tissues and peripheral blood CTC might provide useful information about predicting prognosis of hepatocellular carcinoma. The expression of CD133 in tissues can be used as an important survival predictor of hepatocellular carcinoma patients. The differential expression of cancer markers in tissue samples and blood samples can provide more clinical prognostic information.
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Objective:To investigate the influencing factors for lung metastasis of hepato-cellular carcinoma after liver transplantation and application value of its nomogram prediction model.Methods:The retrospective cohort study was conducted. The clinicopathological data of 339 hepatocellular carcinoma patients with lung metastasis after liver transplantation who were admitted to Zhongshan Hospital of Fudan University from January 2015 to June 2019 were collected. There were 299 males and 40 females, aged from 23 to 73 years, with a median age of 54 years. According to the random numbers showed in the computer, all 339 patients were divided into training dataset consisting of 226 and validation dataset consisting of 113, with a ratio of 2:1. All patients underwent classic orthotopic liver transplantation. Observation indicators: (1) analysis of clinicopathological data of patients in the training dataset and validation dataset; (2) follow-up; (3) analysis of influencing factors for lung metastasis of hepatocellular carcinoma after liver transplanta-tion; (4) construction and evaluation of nomogram prediction model for lung metastasis of hepatocellular carcinoma after liver transplantation. Follow-up was conducted using outpatient examination and telephone interview to detect lung metastasis of patients up to November 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the paired t test. Measurement data with skewed distribution were represented as M( P25, P75) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute number or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate lung metastasis rate and draw lung metastasis curve. The Log-rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analysis. Based on the results of multivariate analysis, the nomogram prediction model was constructed. The prediction accuracy of the nomogram model was evaluated using C-index and receiver operating characteristic (ROC) curve. The calibration curve was used to evaluate the prediction error of the model. Results:(1) Analysis of clinicopathological data of patients in the training dataset and validation dataset: there was no significant difference in general data between patients in the training dataset and validation dataset ( P>0.05). (2) Follow-up: 226 patients in training dataset and 113 patients in validation dataset were followed up. The follow-up time of training dataset was 5.2 to 69.0 months, with a median follow-up time of 29.3 months, and the follow-up time of validation dataset was 4.3 to 69.0 months, with a median follow-up time of 30.4 months. Up to the last follow-up, 48 cases of the training dataset and 22 cases of the validation dataset had lung metastasis, with the incidence and median time of lung metastasis were 21.24%(48/226), 19.47%(22/113) and 8.5 months, 7.8 months, respectively. There was no significant difference in lung metastasis between patients in the training dataset and validation dataset ( χ2=0.144, P>0.05). (3) Analysis of influencing factors for lung metastasis of hepatocellular carcinoma after liver transplantation: results of univariate analysis showed that age, alpha fetoprotein, tumor diameter, tumor differentiation degree, vascular invasion, systemic immune inflammation index and postoperative treatment were related factors for lung metastasis of hepatocellular carcinoma after liver transplantation ( hazard ratio=0.465, 3.413, 1.140, 3.791, 2.524, 2.053, 1.833, 95% confidence interval as 0.263?0.822, 1.740?6.695, 1.091?1.191, 1.763?8.154, 1.903?3.349, 1.047?4.027, 1.038?3.238, P<0.05) . Results of multivariate analysis showed that age, tumor diameter and vascular invasion were independent influencing factors for lung metastasis of hepatocellular carcinoma after liver transplantation ( hazard ratio=0.462, 1.076, 2.170, 95% confidence interval as 0.253?0.843, 1.013?1.143, 1.545?3.048, P<0.05). (4) Construction and evaluation of nomogram prediction model for lung metastasis of hepatocellular carcinoma after liver transplantation: the C-index was 0.810 (95% confidence interval as 0.758?0.863) and 0.802 (95% confidence interval as 0.723?0.881) of the nomogram prediction model for lung metastasis of hepatocellular carcinoma after liver transplanta-tion in the training dataset and validation dataset, respectively, showing good discrimination ability. The area under ROC of 0.5-, 1- and 2-year nomogram prediction model in the training dataset and the validation dataset were 0.815(95% confidence interval as 0.725?0.905), 0.863(95% confidence interval as 0.809?0.917), 0.835(95% confidence interval as 0.771?0.900)and 0.873(95% confidence interval as 0.801?0.945), 0.858(95% confidence interval as 0.760?0.956), 0.841(95% confidence interval as 0.737?0.945), respectively, which illustrated that the model had good predictive ability. The formula of nomogram prediction model=33.300 06+(?33.300 06)×age(≤50 years=0, >50 years=1)+2.857 14×tumor diameter (cm)+31.585 71×vascular invasion (M0 stage of microvascular invasion staging=0, M1 stage of microvascular invasion staging=1, M2 stage of microvascular invasion staging=2, visible tumor thrombus=3). The optimal threshold of nomogram risk score was 77.5. Patients with risk score ≥77.5 were assigned into high risk group, and patients with risk score <77.5 were assigned into low risk group. The 0.5-,1- and 2-year lung metastasis rate of patients in the high risk group and low risk group of the training dataset were 16.7%, 39.2%, 46.4% and 1.4%, 4.1%, 6.9%, respectively, showing a significant difference between the two groups ( χ2=54.86, P<0.05). The 0.5-,1- and 2-year lung metastasis rate of patients in the high risk group and low risk group of the validation dataset were 17.6%, 29.0%, 39.5% and 0, 3.1%, 4.8%, respectively, showing a significant difference between the two groups ( χ2=25.29, P<0.05). Conclusions:Age, tumor diameter and vascular invasion are independent influencing factors for lung metastasis of hepatocellular carcinoma after liver transplantation. The nomogram prediction model based on age, tumor diameter and vascular invasion can predict risk of lung metastasis for hepatocellular carcinoma patients after liver transplantation accurately.
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The Corona Virus Disease 2019 (COVID-19) that occurred December of 2019 has a wide range of impacts, and its epidemic situation is grim. China has a large population of liver cancer, accounting for 50% of new cases of liver cancer worldwide. How to ensure the diagnosis, treatment and rehabilitation of liver cancer patients while preventing and controlling the epidemic situation is an issue that urgently need specialists pay attention to. The authors propose an overall management model for patients with liver cancer, combined with their own experience, in order to guide specialists to safely and effectively carry out clinical diagnosis and treatment of liver cancer during the prevention and control of epidemics, and to help liver cancer patients receive treatment.
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Although the epidemic situation of Corona Virus Disease 2019 (COVID-19) has been controlled, the epidemic situation remains grim. The COVID-19 is highly infectious, with various clinical manifestations including liver injury. The authors make a preliminary investigation on the mechanisms of liver injury related to COVID-19, and put forward correspon-ding control measures for reference.
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Precision medicine is currently being paid much attention and greatly promotes the diagnosis and treatment of various diseases,especially cancer.Surgery plays a pivotal role in the treatment of hepatocellular carcinoma (HCC) and precision hepatectomy stands as the most updated surgical idea.Application of the concept and techniques of precision medicine to further improve HCC surgery,consummate the skills and modalities of HCC surgical treatment,enrich the nature of precision hepatectomy,so as to make precise evaluation,early prediction,reduce postoperative recurrence and metastasis,find biomarkers of molecular targeted therapy and improve the prognosis is the prime task of HCC surgery.
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Objective To investigate the concentrations of serum N-terminal brain natriuretic peptide (NT-pm BNP) and high-sensitivity C-reactive protein (hs-CRP) of acute exacerbation of chronic obstrnctive pulmonary disease(AECOPD) patients treated by bi-level positive airway pressure(BiPAP) for with respiratory failure.Methods A total of 100 respiratory failure in patients with AECOPD were divided into study group and control group,and 50 cases of each group.Patients in study group were received the conventional treatment(anti infection,diastolic bronchial,cough and phlegm and oxygen therapy) combined with BiPAP therapy,while in control group were received the conventional treatment.Blood samples were drawn at beginning and 3 d later.Serum hs-CRP and NT-pro BNP levels were determined,and the expenses and duration of hospitalization of two groups were compared.Result After treatment,the level of serum NT-pro BNP in study group and control group were (105.79 ± 4.56) ng/L and (113.33 ± 3.26) ng/L,and the difference was statistically signifi cant (t =3.03,P ＜ 0.05).The serum hs-CRP levels were (10.83 ± 16.35) mg/L and (26.39 ± 26.87) mg/L in study and control group,and the differences were statistically significant (t =-3.44,P ＜ 0.05).The expenses and duration of hospitalization in study group were both less than those in control group((11.15 ± 1.86) d vs.(12.78±2.25) d;(6 659.11 ±1 609.49) yuan vs.(8 031.31 ±1 449.79) yuan;t=-3.87,-4.38;P ＜0.05).Conclusion Early BiPAP therapy in AECOPD patients with respiratory failure in patients is showed that NT-pro BNP and hs-CRP levels faster decrease and disease is recovery remission,which suggests that NTpro BNP or BNP for AECOPD patients and respiratory failure condition monitoring,clinical efficacy have some clinical value.
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Objective To investigate the mouse liver blood vessel images using phase contrast X-ray imaging with synchrotron radiation. Methods 6 female C57BL/6 mice were randomly divided into two groups, 3 mice in each group. In one group, livers excised after hgated arteries, veins and common bile duct. In another group, iodine infused via the portal vein and drained from inferior vena cave until all the blood in the portal veins and hepatic veins was displaced. After infusion, arteries, veins and common bile duct were ligated and livers were excised. Results Blood vessel images were clearly produced by diffraction enhanced imaging. This method can discriminate vessels down to about 40 μm in diameter without contrast agent. Using a contrasting agent more details could be produced. In one liver lobe, the entire branch of the portal vein could be clearly produced by one by one phase contrast image from the main axial blood vessels of liver lobe to the nine generation of branching. Conclusions Phase contrast imaging has the advantage of good contrast and high spatial resolution. [Key wnrds] Synchrotron radiation; Phase contrast imaging; Diffraction enhanced imaging; Blood vessel; X-rays