Efficacy and safety of lenvatinib combined with sintilimab as the second-line therapy for intrahepatic cholangiocarcinoma / 临床肝胆病杂志

Objective To investigate the efficacy and safety of lenvatinib combined with sintilimab as the second-line therapy for advanced intrahepatic cholangiocarcinoma (ICC). Methods A retrospective analysis was performed for the clinical data of the patients with advanced ICC who were admitted to Beijing Ditan Hospital from October 31, 2019 to October 31, 2021 and could not undergo surgery or experienced metastasis after surgery. All patients were treated with lenvatinib combined with sintilimab as the second-line therapy. The patients were followed up, and the RECIST1.1 criteria were used to assess treatment outcome. The primary endpoint was time to progression (TTP), and the secondary endpoints were tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS) time, and safety. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison between groups. Results A total of 27 patients were enrolled, among whom there were15 male patients (55.6%) and 12 female patients (44.4%), with a median age of 58 years (range 33-73 years). The median TTP for these patients was 5.5 (95% confidence interval [ CI ]: 1.7-9.3) months, and 13 patients (48.1%) died of disease progression, with a median OS time of 11.2 (95% CI : 5.0-17.4) months. The overall ORR and DCR were 40.7% and 70.3%, respectively. Of all patients, 66.7% experienced varying degrees of adverse events, and among these patients, 44.4% had an increase in alanine aminotransferase, 44.4% had an increase in aspartate aminotransferase, 37.0% had hypertension, 29.6% had an increase in bilirubin, 29.6% experienced diarrhea, and 25.9% each experienced proteinuria, anorexia, and weakness. No treatment-related death was observed, and only 1 patient developed grade Ⅳ immune-related hepatotoxicity and was relieved without sequelae after corticosteroid therapy, resulting in permanent withdrawal of sintilimab. The patients with lymph node metastasis had a significantly shorter median TTP than those without lymph node metastasis (4.5 months vs 18.8 months, P =0.035), and the patients who achieved disease remission had a significantly longer median TTP [11.6 months (95% CI : 5.6-17.6) vs 2.8 months (95% CI : 1.8-3.8), P < 0.001]; the patients with lymph node metastasis had a shorter median OS time [9.6 months (95% CI: 7.9-11.3) vs 21.9 months (95% CI : 0-44.9), P =0.053], and the patients who achieved disease remission had a significantly longer median OS time [16.6 months (95% CI : 9.0-24.2) vs 6.9 months (95% CI : 3.6-10.2), P =0.011]. Conclusion Lenvatinib combined with sintilimab has a marked clinical effect and a low incidence rate of serious adverse events as the second-line therapy for advanced ICC, and therefore, it is a safe and effective treatment regimen.

Efficacy and safety of lenvatinib in patients with unresectable hepatocellular carcinoma previously treated with tyrosine kinase inhibitor / 临床肝胆病杂志

Objective To investigate the efficacy and safety of lenvatinib in patients with unresectable hepatocellular carcinoma (HCC) previously treated with tyrosine kinase inhibitor (TKI). Methods A retrospective analysis was performed for the clinical data of 76 patients with unresectable HCC who were treated with lenvatinib in Beijing Ditan Hospital, Capital Medical University, from January 2019 to January 2020, and according to the treatment method, they were divided into TKI previously untreated group with 49 patients and TKI treatment-experienced group with 27 patients. The patients were observed till one year after enrollment, adjustment of treatment regimen, tumor progression, or death. The two groups were compared in terms of progression-free survival (PFS) time, objective response rate (ORR), disease control rate (DCR), and incidence rate of adverse events. The t -test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test or the Wilcoxon rank-sum test was used for comparison of categorical data between two groups; the Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison between groups. Results There were no significant differences between the TKI previously untreated group and the TKI treatment-experienced group in median PFS time (115 days vs 72 days, P =0.148), ORR (36.7% vs 18.5%, P =0.098), DCR (65.3% vs 55.6%, P =0.402), and incidence rates of grade ≥3 adverse events (24.5% vs 18.5%, P =0.550). Conclusion Patients with unresectable HCC previously treated with TKI can benefit from lenvatinib and have good safety, with similar results to those treated with TKI for the first time.

Clinical effect of programmed cell death-1 inhibitor combined with lenvatinib in treatment of advanced primary liver cancer and related adverse events / 临床肝胆病杂志

ObjectiveTo investigate the clinical effect of domestic programmed cell death-1 (PD-1) inhibitor combined with lenvatinib in the treatment of advanced primary liver cancer and related adverse events. MethodsA retrospective analysis was performed for the clinical data of 24 patients with advanced primary liver cancer who were treated with domestic PD-1 inhibitor combined with lenvatinib in Beijing Ditan Hospital, Capital Medical University, from January 1, 2019 to April 2, 2020, with 15 patients in the Camrelizumab+lenvatinib group, 7 patients in the Sintilimab+lenvatinib group, and 2 patients in the Toripalimab+lenvatinib group. During follow-up, Modified Response Evaluation Criteria in Solid Tumors was used to evaluate the treatment outcome of intrahepatic lesions, and RECIST1.1 was used to evaluate extrahepatic metastatic lesions. The Kaplan-Meier method was used to evaluate survival time. ResultsAmong the 24 treatment-experienced patients, 11 achieved partial response, 7 achieved a stable disease, and 6 had disease progression, resulting in an objective response rate of 45.8% and a disease control rate of 75.0%. The median time to disease progression was 8.4 (95% confidence interval: 6.89-9.91) months. The incidence rate of adverse events was 54.17%, and the most common adverse events were fatigue (29.17%) and hypertension (25.00%). ConclusionPD-1 inhibitor combined with lenvatinib has a marked clinical effect in the treatment of advanced primary liver cancer, with a low incidence rate of serious adverse events, and thus it is a safe and effective treatment regimen.

Advances in lung epithelial stem cells / 国际儿科学杂志

An in-depth understanding of the relevant cell types and mechanisms of lung regeneration has an important positive effect on the prevention and treatment of lung diseases.This review summarizes the recent advances in the classification, characteristics, and mechanisms of self-renewal and differentiation of lung epithelial stem cells.Lung epithelial stem cells include basal cells, club cells, pulmonary neuroendocrine cells, bronchioloalveolar stem cells, distal airway stem cells and alveolar epithelial stem cells.Mechanisms include Wnt, notch, innate immune signaling pathways and others related to growth factors and transcription factors.

Advances in targeted therapy and immunotherapy for hepatocelluar carcinoma / 临床肝胆病杂志

There are still high incidence and mortality rates of hepatocellular carcinoma at present, and systemic treatment plays an important role in the treatment of advanced hepatocellular carcinoma. This article describes the application of molecular-targeted drugs and immune checkpoint inhibitors in hepatocellular carcinoma and points out that dual-targeted therapy, dual immunotherapy, and targeted therapy combined with immunotherapy are the current research hotspots in the treatment of hepatocellular carcinoma.

Clinical effect and safety of radiofrequency ablation combined with systemic chemotherapy in treatment of unresectable or postoperative recurrent intrahepatic cholangiocellular carcinoma / 临床肝胆病杂志

ObjectiveTo investigate the clinical effect and safety of percutaneous radiofrequency ablation (RFA) combined with systemic chemotherapy in the treatment of unresectable or postoperative recurrent intrahepatic cholangiocellular carcinoma. MethodsThe patients with unresectable or postoperative recurrent cholangiocellular carcinoma who were treated from January 2011 to December 2016 were enrolled. All patients underwent CT-guided RFA, followed by systemic chemotherapy since one week after surgery, with the regimen of gemcitabine given concurrently with cisplatin (gemcitabine 1000 mg/m2 combined with cisplatin 25 mg/m2 on days 1 and 8, for 6 cycles in total). Treatment outcome and safety were observed. ResultsThere were 45 lesions in total, and RFA and chemotherapy were performed for all lesions. The overall objective response rate was 79.2%. The complete ablation rate of the lesions at one month after surgery was 86.7% (39/45). The patients were followed up for 11-67 months after surgery, and at the end of follow-up, the rate of local progression was 200% (9/45). The median time to progression was 13.0 months, the median survival time was 28.6 months, and the 1-, 2-, and 3-yaer survival rates were 87.3%, 69.3%, and 32.6%, respectively. Major side effects included hematological toxicity and elevated aminotransferases, and there were no serious adverse events associated with RFA. ConclusionRFA combined with systemic chemotherapy is a safe and feasible regimen for unresectable or postoperative recurrent intrahepatic cholangiocellular carcinoma.

The combination of percutaneous iohexol-ethanol injection with radiofrequency ablation for the treatment of primary liver cancer in high-risk locations / 中华肿瘤杂志

Objective@#To investigate the safety and efficacy of radiofrequency ablation (RFA) with percutaneous iohexol-ethanol injection (PIEI), compared with RFA plus transcatheter arterial chemoembolization (TACE) for patients with primary liver cancer(PLC)in high-risk locations.@*Methods@#From January 2012 to December 2014, 54 patients with PLC in high-risk locations were enrolled. They were divided into Group A (RFA combined with PIEI) and Group B (RFA plus TACE). The efficacy and adverse events were assessed.@*Results@#54 patients had 74 lesions in high-risk locations. There were 26 cases with 40 lesions in Group A, and 28 cases with 34 lesions in Group B. The complete ablation rate of Group A was significantly higher than that of Group B (92.5% vs 70.6%, P=0.014). The two-year local tumor progressionrateand two-year overall survival rate were similar between these two groups (Group A 20.0% vs Group B 38.2%, P=0.083; 90.3% vs 84.3%, P=0.523). Furthermore, the surgery-related severe adverse events of Group A (7.1%, one case of liver abscess and one case ofhematobilia) were more common than that of Group B (0%, P=0.491). No significant differences were found in common adverse events including fever, pain, elevation of aminotransferase and bilirubin.@*Conclusions@#Compared with RFA plus TACE, RFA plus PIEI resulted inbetter complete ablation rate in patients with primary liver cancer in high risk locations. Prospective, randomized, controlled trials are warranted for further evaluation.

Clinical effect and safety of percutaneous radiofrequency ablation following transcatheter arterial chemoembolization in treatment of primary liver cancer in high-risk locations / 临床肝胆病杂志

ObjectiveTo investigate the clinical effect and safety of percutaneous radiofrequency ablation (RFA) following transcatheter arterial chemoembolization (TACE) in the treatment of primary liver cancer in high-risk locations. MethodsThe patients with primary liver cancer in high-risk locations who were diagnosed and treated from January 2011 to December 2015 were enrolled. All the patients underwent TACE followed by CT-guided RFA 3-5 days later. The treatment outcome and adverse events were observed. ResultsA total of 64 patients with 76 lesions were enrolled and all of them completed TACE and RFA. At one month after surgery, the complete tumor ablation rate was 81.5% (62/76). The patients were followed up for 6 to 64 months after surgery; at the end of follow-up, the local tumor progression rate was 28.9% (22/76), and the 1-, 2-, and 3-year survival rates were 90.6%, 78.1%, and 64.1%, respectively. The incidence rate of severe surgical complications during follow-up was 3.1% (one patient each experienced liver abscess and hematobilia), and the patients achieved remission after medical treatment and interventional treatment without any sequel. ConclusionCT-guided RFA after TACE is a safe and feasible regimen for primary liver cancer in high-risk locations.

Drug resistance detection of virus genotype in hepatitis B and analysis of its clinical factors / 国际检验医学杂志

Objective To explore the related factors of hepatitis B virus(HBV) drug resistance and their clinical significance . Methods The retrospective analysis was performed on the dinical data in 153 cases of CHB in our hospital during 2011-2013 .The 8 viral drug resistance loci of 4 known nucleosides analogues lamivudine ,adefovir ester ,entecavir and telbivudine were performed the direct sequencing by using the double DNA end termination method(Sanger method);the related clinical factors of drug‐resist‐ant virus genotypes were statistically analyzed and the correlation between prognosis and drug resistance was analyzed .Results A‐mong 153 patients with CHB ,47 cases(29 .8% ) appeared virus genotype drug‐resistant ,the common sites were 204M‐I(18 cases) , 204M‐V(8 cases) ,followed by 181A‐T(10 cases) ,181A‐V(5 cases) ,then 180L‐M (14 cases) .The proportion of viral drug resist‐ance in the patients with family history ,HBeAg positive ,using the nucleotide analogues in the past and the baseline ALT≥5 times was significantly increased ,the incidence rates were 38 .8% ,34 .8% ,34 .6% and 50 .0% respectively .The multivariable COX re‐gression found that HBV‐DNA genetic drug resistance increased the risk of progression to cirrhosis of the liver ,the OR value was 4 .704(95% CI:1 .199 -18 .454) .Conclusion the Sanger method for direct sequencing is reliable and accurate method of HBV‐DNA genotype drug resistance .The proportion of viral drug resistance in the patients with a family history of hepatitis B ,HBeAg positive ,using nucleotide analogues and baseline ALT≥5 times is significantly increased;HBV‐DNA genotype drug resistance also increases the risk of progression to cirrhosis of the liver .

Identification, structure and function of a novel tetraspaninhomologue from Spirometra erinaceieuropaei.

OBJECTIVE: To identify a full length c DNA sequence of a novel tetraspanin (TSP) homologue from Spirometra erinaceieuropaei and to predict the structure and function of its encoding protein using bioinformatics methods. METHODS: Using the NCBI, EMBI, Expasy and other online sites, the open reading frame (ORF), conserved domain, physical and chemical parameters, signal peptide, transmembrane domain, epitope, topological structures of the protein sequences were predicted. And Vector NTI software was used for multiple sequence alignment and phylogenetic tree construction. RESULTS: The target sequence was 1132 bp length with a 681 bpbiggest ORF encoding 226 amino acids protein with typical TSP conserved domain. It was confirmed as full length c DNA of TSP16 from Spirometra erinaceieuropaei and named as SeTSP16 (GenBank accession number: JF728872). The predicted molecular weight and isoelectric point of the deduced protein were 24 750.5 Da and 7.88 Da, respectively. Compared with TSP16s from Schistosoma japonicum and Schistosoma mansoni, it showed similarity of 59% and 59%, respectively. SeTSP16 contained four transmembrane domains (TM1-4), intracellular N and C-termini, one short small extracellular loop and one large extracellular loop. Four major epitopes that were significant different from the corresponding epitope regions of TSP16 from Schistosoma mansoni and Schistosoma japonicum were predicted. CONCLUSIONS: The full length c DNA sequences of SeTSP16 are identified. It encodes a transmembrane protein which might be an ideal diagnosis antigen and target molecule for antiparasitic drugs.