1.Safety and efficacy analysis of TACE combined with donafenib and PD-1 inhibitors in the treatment of unresectable hepatocellular carcinoma
Daqian HAN ; Wenze XU ; Chao LIANG ; Hao LI ; Shuguang JU ; Manzhou WANG ; Jiacheng WANG ; Yang-yang NIU ; Xinwei HAN ; Jianzhuang REN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2025;31(7):503-509
Objective:To compare the safety and efficacy of transarterial chemoembolization (TACE) combined with donafenib and programmed death protein 1 (PD-1) inhibitors and TACE combined with donafenib in the treatment of unresectable hepatocellular carcinoma (uHCC).Methods:Clinical data of 148 patients with uHCC treated at the First Affiliated Hospital of Zhengzhou University from December 2021 to December 2022 were retrospectively analyzed, including 127 males and 21 females, aged (56.6±9.9) years. Patients were divided into two groups: the TACE combined with donafenib and PD-1 inhibitors group (TACE+ DP, n=73) and TACE combined with single donafenib (TACE+ D, n=75). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and the occurrence of treatment-related adverse events (TRAEs) of the two groups of patients were observed. Kaplan-Meier analysis was used for survival assessment, and the log-rank test was used for comparison. The related factors affecting the prognosis of patients were indentified and analyzed. Results:The median PFS of patients in the TACE+ D group and the TACE+ DP group were 7.2 months (95% CI: 5.7-8.3 months) and 10.5months (95% CI: 8.9-11.3 months), respectively. The median OS was 13.2 months (95% CI: 12.3-13.7 months) and 16.9 months (95% CI: 15.1-19.8 months), respectively. All these differences were statistically significant ( χ2=17.81, 26.92, respectively, both P<0.001). The ORR and DCR of TACE+ DP group were both higher than those in TACE+ D group [53.4% (39/73) vs 36.0% (27/75), χ2=4.55, P=0.031; and 90.4% (66/73) vs 77.3% (58/75), χ2=4.66, P=0.044]. No grade 4 or above adverse events occurred in either the TACE+ DP or the TACE+ D group. The most common treatment-related adverse events in TACE+ D and TACE+ DP group were hand-foot syndrome [46.7% (35/75) vs 49.3% (36/73)], hypertension [26.7% (20/75) vs 30.1% (22/73)], fatigue [22.7% (17/75) vs 24.7% (18/73)], diarrhea [26.7% (20/75) vs 28.8% (21/73)], and thrombocytopenia [25.3% (19/75) vs 28.8% (21/73)]. There was no significant difference in the incidence and severity of TRAEs between the groups ( χ2=0.08, P=0.774). TACE+ DP treatment was a favorable prognostic factor for PFS ( HR=0.33, 95% CI: 0.22-0.49, P<0.001) and OS ( HR=0.19, 95% CI: 0.11-0.33, P<0.001) of patients. Conclusion:Compared to TACE combined with donafenib, TACE combined with donafenib and PD-1 inhibitors, with good efficacy and safety, significantly improved the treatment response and survival in patients with uHCC.
2.Clinical study of TACE combined with apatinib for advanced hilar cholangiocarcinoma
Daqian HAN ; Hao LI ; Chao LIANG ; Manzhou WANG ; Yangyang NIU ; Shuguang JU ; Jiacheng WANG ; Jianzhuang REN ; Xinwei HAN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2025;31(4):262-267
Objective:To study the safety and feasibility of transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hilar cholangiocarcinoma.Methods:Clinical data of 41 patients with hilar cholangiocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University from November 2019 to October 2020 were prospectively collected, including 21 males and 20 females, aged (65.1±12.5) years. The drugs used for TACE were albumin paclitaxel and gemcitabine, which were performed once every four to six weeks for no more than six times. Apatinib were adminstered two days after each TACE. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events. Patients were followed-up by outpatient, inpatient or telephone review. Survival analysis was performed using the Kaplan-Meier method.Results:Hilar cholangiocarcinoma were confirmed in all 41 patients by pathology. All patients were treated with TACE for at least twice. Twenty-three patients achieved complete remission, 14 stable disease, and four partial remission, with an ORR of 56.1% and a disease control rate of 90.2%. The follow-up duration was (13.3±5.4) months without lost to follow-up. The median PFS was 9.0 months, the median OS was 14.0 months, the 1-year cumulative recurrence-free survival rate was 31.7%, and the 1-year cumulative survival rate was 65.9%. Treatment-related adverse events in this study were predominantly Clavien-Dindo grade 1 or 2, without grade 4 to 5.Conclusion:TACE combined with apatinib treatment could be safe and feasible for advanced hilar cholangiocarcinoma.
3.Clinical study of TACE combined with apatinib for advanced hilar cholangiocarcinoma
Daqian HAN ; Hao LI ; Chao LIANG ; Manzhou WANG ; Yangyang NIU ; Shuguang JU ; Jiacheng WANG ; Jianzhuang REN ; Xinwei HAN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2025;31(4):262-267
Objective:To study the safety and feasibility of transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hilar cholangiocarcinoma.Methods:Clinical data of 41 patients with hilar cholangiocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University from November 2019 to October 2020 were prospectively collected, including 21 males and 20 females, aged (65.1±12.5) years. The drugs used for TACE were albumin paclitaxel and gemcitabine, which were performed once every four to six weeks for no more than six times. Apatinib were adminstered two days after each TACE. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events. Patients were followed-up by outpatient, inpatient or telephone review. Survival analysis was performed using the Kaplan-Meier method.Results:Hilar cholangiocarcinoma were confirmed in all 41 patients by pathology. All patients were treated with TACE for at least twice. Twenty-three patients achieved complete remission, 14 stable disease, and four partial remission, with an ORR of 56.1% and a disease control rate of 90.2%. The follow-up duration was (13.3±5.4) months without lost to follow-up. The median PFS was 9.0 months, the median OS was 14.0 months, the 1-year cumulative recurrence-free survival rate was 31.7%, and the 1-year cumulative survival rate was 65.9%. Treatment-related adverse events in this study were predominantly Clavien-Dindo grade 1 or 2, without grade 4 to 5.Conclusion:TACE combined with apatinib treatment could be safe and feasible for advanced hilar cholangiocarcinoma.
4.Safety and efficacy analysis of TACE combined with donafenib and PD-1 inhibitors in the treatment of unresectable hepatocellular carcinoma
Daqian HAN ; Wenze XU ; Chao LIANG ; Hao LI ; Shuguang JU ; Manzhou WANG ; Jiacheng WANG ; Yang-yang NIU ; Xinwei HAN ; Jianzhuang REN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2025;31(7):503-509
Objective:To compare the safety and efficacy of transarterial chemoembolization (TACE) combined with donafenib and programmed death protein 1 (PD-1) inhibitors and TACE combined with donafenib in the treatment of unresectable hepatocellular carcinoma (uHCC).Methods:Clinical data of 148 patients with uHCC treated at the First Affiliated Hospital of Zhengzhou University from December 2021 to December 2022 were retrospectively analyzed, including 127 males and 21 females, aged (56.6±9.9) years. Patients were divided into two groups: the TACE combined with donafenib and PD-1 inhibitors group (TACE+ DP, n=73) and TACE combined with single donafenib (TACE+ D, n=75). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and the occurrence of treatment-related adverse events (TRAEs) of the two groups of patients were observed. Kaplan-Meier analysis was used for survival assessment, and the log-rank test was used for comparison. The related factors affecting the prognosis of patients were indentified and analyzed. Results:The median PFS of patients in the TACE+ D group and the TACE+ DP group were 7.2 months (95% CI: 5.7-8.3 months) and 10.5months (95% CI: 8.9-11.3 months), respectively. The median OS was 13.2 months (95% CI: 12.3-13.7 months) and 16.9 months (95% CI: 15.1-19.8 months), respectively. All these differences were statistically significant ( χ2=17.81, 26.92, respectively, both P<0.001). The ORR and DCR of TACE+ DP group were both higher than those in TACE+ D group [53.4% (39/73) vs 36.0% (27/75), χ2=4.55, P=0.031; and 90.4% (66/73) vs 77.3% (58/75), χ2=4.66, P=0.044]. No grade 4 or above adverse events occurred in either the TACE+ DP or the TACE+ D group. The most common treatment-related adverse events in TACE+ D and TACE+ DP group were hand-foot syndrome [46.7% (35/75) vs 49.3% (36/73)], hypertension [26.7% (20/75) vs 30.1% (22/73)], fatigue [22.7% (17/75) vs 24.7% (18/73)], diarrhea [26.7% (20/75) vs 28.8% (21/73)], and thrombocytopenia [25.3% (19/75) vs 28.8% (21/73)]. There was no significant difference in the incidence and severity of TRAEs between the groups ( χ2=0.08, P=0.774). TACE+ DP treatment was a favorable prognostic factor for PFS ( HR=0.33, 95% CI: 0.22-0.49, P<0.001) and OS ( HR=0.19, 95% CI: 0.11-0.33, P<0.001) of patients. Conclusion:Compared to TACE combined with donafenib, TACE combined with donafenib and PD-1 inhibitors, with good efficacy and safety, significantly improved the treatment response and survival in patients with uHCC.
5.Comparison of different timing of empirical antifungal strategy in febrile neutropenic children with acute leukemia
Fan WU ; Yong ZHUANG ; Yuan ZHANG ; Xinwei ZHU ; Xiuli JU
Chinese Pediatric Emergency Medicine 2022;29(7):525-529
Objective:To compare the clinical value of early and deferred empirical antifungal strategies in febrile neutropenic children with acute leukemia.Methods:A total of 101 cases of febrile neutropenic children with acute leukemia hospitalized in Qilu Hospital of Shandong University from January 2019 to June 2021 were divided into two groups according to different empirical antifungal strategies.There were 41 cases in early group in which antifungal therapy was given within 4 days of fever, and 60 cases in deferred group in which antifungal therapy was not given within 4 days of fever.Outcomes such as time to stable defervescence, positive diagnosis rate of invasive fungal disease, incidence of severe pneumonia, rate of transference to PICU, exposure time and costs of antifungal agents, and infection-related hospitalization days were compared between two groups.Results:There were no significant differences in time to stable defervescence[5 (4, 7) days vs.5 (3, 7) days, P=0.986], positive diagnosis rate of invasive fungal disease[9.8%(4/41) vs.8.3%(5/60), P=1.000], incidence of severe pneumonia[19.5%(8/41) vs.10.0%(6/60), P=0.174], and rate of transference to PICU[2.4%(1/41)vs.0(0/60), P=0.406] between two groups.Exposure time of antifungal agents was longer in early group than that in deferred group[10 (6, 12)days vs.0 (0, 6)days, P<0.001]. Costs of antifungal agents were higher in early group than those in deferred group[0.78(0.51, 0.95)ten thousand yuan vs.0(0, 0.44)ten thousand yuan, P<0.001]. Infection-related hospitalization days were longer in early group than those in deferred group[16 (10, 21) days vs.9(6, 13)days, P<0.001]. Conclusion:For febrile neutropenic children with acute leukemia, clinical effect of early empirical antifungal strategy is not superior to that of deferred empirical antifungal strategy.Pediatricians should make reasonable antifungal decisions according to overall situation of patients.
6.A cost-effect analysis of transarterial chemoembolization with CalliSpheres beads loaded with arsenic trioxide versus arsenic trioxide iodized oil emulsion in treatment of unresectable liver cancer
Wenhui WANG ; Xuhua DUAN ; Hao LI ; Shuguang JU ; Manzhou WANG ; Jianzhuang REN ; Xinwei HAN
Journal of Clinical Hepatology 2021;37(9):2125-2129
Objective To investigate the cost-effect of transarterial chemoembolization (TACE) with CalliSpheres beads loaded with arsenic trioxide (ATO) (CBATO) versus ATO iodized oil emulsion (conventional TACE, cTACE) in the treatment of unresectable liver cancer. Methods A total of 100 patients with advanced liver cancer who attended The First Affiliated Hospital of Zhengzhou University from May 2017 to December 2018 were enrolled and divided into CBATO group( n =45) and cTACE group( n =55) according to the treatment regimen. Progression-free survival (PFS) was used to evaluate the efficacy of quality-adjusted life year (QALY), and European Quality of Life-5 Dimensions (EQ-5D) index was used to evaluate quality of life. The t -test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; the number of surgeries, length of hospital stay, treatment cost, and incremental cost-effectiveness ratio (ICER) were calculated for the two groups, and then a cost-effect analysis was performed. Results Within the PFS time, the per capita hospital cost was 96 446 yuan in the CBATO group and 91 230.43 yuan in the cTACE group. There were significant differences between the two groups in the mean number of surgeries (2.5±0.7 vs 3.4±0.8, t =16.911, P < 0.01) and mean hospital stay (5.8±1.2 days vs 7.5±1.8 days, t =12.459, P < 0.01). The CBATO group had a significantly higher QALY than the cTACE group (0.804 vs 0.512). Compared with the cTACE group, the CBATO group had an ICER of 17 861.53 yuan/QALY for unresectable liver cancer. Conclusion Although CBATO has a higher surgery cost than cTACE, CBATO has a better clinical effect than cTACE and can reduce the number of surgeries and length of hospital stay, with a better postoperative quality of life than cTACE, suggesting that CBATO has marked cost-effect advantages.
7.Effect of arsenic trioxide-loaded CalliSpheres beads in the treatment of rabbits with VX2 liver tumor
Wenhui WANG ; Xuhua DUAN ; Hao LI ; Fengyao LI ; Shuguang JU ; Manzhou WANG ; Jianzhuang REN ; Xinwei HAN
Journal of Clinical Hepatology 2020;36(12):2730-2734
ObjectiveTo investigate the effect of arsenic trioxide-loaded CalliSpheres beads (CBATO) in transarterial chemoembolization (TACE) in the treatment of rabbits with VX2 liver tumor. MethodsA total of 120 tumor-bearing rabbits were divided into control group, CalliSpheres beads (CB) group (blank beads for TACE), CBATO group, and conventional TACE (cTACE) group (arsenic trioxide lipiodol for TACE) using a random number table, with 30 rabbits in each group. Five rabbits in each group were sacrificed at 12 hours and on days 3, 7, and 14 after TACE, and immunohistochemistry was used to measure the proliferation index and apoptosis percentage of tumor cells in the residual tumor area. The tumor necrotic volume was measure on day 7 after TACE, and the growth rate and necrosis rate of tumor cells were calculated. Ten rabbits were randomly selected from each group for the observation of survival time. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kaplan-Meier survival analysis was used to evaluate survival time, and the log-rank test was used for comparison. ResultsOn day 7 after TACE, the CBATO group had a significantly lower growth rate and a significantly higher necrosis rate of tumor cells than the cTACE group, the CB group, and the control group (all P<0.05). At each time point after TACE, there were significant differences in the proliferation index and apoptosis percentage of tumor cells between the CBATO group and the other three groups (all P<0.05). The median survival time was 26 days in the CBATO group, 18.5 days in the CB group, 22 days in the cTACE group, and 15.5 days in the control group, and the CBATO group had a significantly longer survival time than the other three groups (χ2=3.95, 8.99, and 13.47, P=0.049, P=0.003, and P<0.01). ConclusionCBATO has a better effect than cTACE and CB in the treatment of rabbits with VX2 liver tumor and can significantly improve tumor necrosis rate, promote the apoptosis of tumor cells, and prolong the survival time of experimental animals.
8.Detection of white blood cells in microscopic leucorrhea images based on deep active learning.
Mengxi JU ; Xinwei LI ; Zhangyong LI
Journal of Biomedical Engineering 2020;37(3):519-526
The number of white blood cells in the leucorrhea microscopic image can indicate the severity of vaginal inflammation. At present, the detection of white blood cells in leucorrhea mainly relies on manual microscopy by medical experts, which is time-consuming, expensive and error-prone. In recent years, some studies have proposed to implement intelligent detection of leucorrhea white blood cells based on deep learning technology. However, such methods usually require manual labeling of a large number of samples as training sets, and the labeling cost is high. Therefore, this study proposes the use of deep active learning algorithms to achieve intelligent detection of white blood cells in leucorrhea microscopic images. In the active learning framework, a small number of labeled samples were firstly used as the basic training set, and a faster region convolutional neural network (Faster R-CNN) training detection model was performed. Then the most valuable samples were automatically selected for manual annotation, and the training set and the corresponding detection model were iteratively updated, which made the performance of the model continue to increase. The experimental results show that the deep active learning technology can obtain higher detection accuracy under less manual labeling samples, and the average precision of white blood cell detection could reach 90.6%, which meets the requirements of clinical routine examination.
9.Study on the enhanced morphology around MRI after DEB-TACE in primary hepatocellular carcinoma
Donglin KUANG ; Jianzhuang REN ; Xuhua DUAN ; Xuemei GAO ; Xinwei HAN ; Wenguang ZHANG ; Pengfei CHEN ; Nan ZHANG ; Yang WANG ; Shuguang JU
Chinese Journal of Hepatobiliary Surgery 2020;26(9):687-690
Objective:To investigate the morphological feature and clinical significance of MRI around tumor after drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) of primary hepatocellular carcinoma.Methods:We reviewed and analyzed the data of hepatocellular carcinoma patients admitted from January 2017 to December 2018 in the Department of Radiological Intervention of the First Affiliated Hospital of Zhengzhou University. A total of 42 patients were enrolled, including 35 males and 7 females, aged (57.0±11.9) years. For the first time after operation, MRI enhancement showed peri-tumor margin enhancement as the starting point of follow-up. Follow-up and measure enhanced edge thickness, delayed enhancement, progression or remission data.Results:A total of 49 tumors and 84 peritumoral enhancement margins were included in 42 patients, with 30 sharp type , 40 rough type and 14 nodular type. The thickness of sharp type is less than that of rough type and nsodular type, and the differences were statistically significant (all P<0.05). The sharp type is the majority of the tumors with maximum diameter <5 cm, rough type and nodule type are the majority of tumors with maximum diameter ≥5 cm. Most of the sharp type are continuously enhanced, while the rough type and nodular type are not. Most sharp type relief (93.3%, 28/30), while rough type (80.0%, 32/40) and nodular type ( n=12) are mostly of deterioration, the differences are statistically significant (all P<0.05). Conclusion:Compared with the rough type and nodular type, the sharp type usually occurs in smaller tumors and more prone to local mitigation in the enhanced morphology around MRI after DEB-TACE in primary hepatocellular carcinoma.

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