1.Efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma
Huilai LYU ; Mingbo WANG ; Chunyue GAI ; Fan ZHANG ; Yonggang ZHU ; Yu LIU ; Jiachen LI ; Weilu DING ; Shi XU ; Zhenhua LI ; Bokang SUN ; Wenda GAO ; Ziqiang TIAN
Chinese Journal of Surgery 2025;63(11):1023-1030
Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.
2.Analysis of risk factors of diaphragmatic hernia after thoraco-laparoscopic minimally invasive McKeown esophagectomy
Zhenhua LI ; Weilu DING ; Huilai LYU ; Bokang SUN ; Keqin DONG ; Mingbo WANG ; Peng SU ; Ziqiang TIAN
Chinese Journal of Surgery 2025;63(2):130-135
Objective:To explore the related risk factors of diaphragmatic hernia after thoraco-laparoscopic minimally invasive Mckeown esophagectomy (MIME).Methods:This is a retrospective controlled study. A retrospective analysis was conducted on the clinical data of patients who underwent MIME at the Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, from January 2016 to December 2023. A total of 619 patients were included. There were 423 males and 196 females, aged (63.7±7.6) years (range: 37 to 87 years). The diagnosis of diaphragmatic hernia after MIME was made based on clinical symptoms and CT scans. Patients were divided into two groups: the diaphragmatic hernia group ( n=16) and the non-diaphragmatic hernia group ( n=603). Clinical data, including age, gender, body mass index (BMI), smoking history, tumor location (upper, middle, and lower thoracic esophagus), preoperative neoadjuvant therapy history, and tumor staging, were collected and analyzed. A BMI of 25 kg/m2 and age of 65 years were used as cutoff values. The χ2 test and Fisher′s exact test were used to compare the data between the two groups, and Logistic regression was employed for risk factor analysis. The diaphragmatic hernia group and non-diaphragmatic hernia group were matched in a 1∶3 ratio with a caliper value of 0.02 by propensity score matching. Kaplan-Meier method was used for survival analysis and compared using the log-rank test for between-group differences. Results:The proportion of patients with diaphragmatic hernia after MIME who underwent surgical treatment was 6/16. Statistically significant differences were observed between the diaphragmatic hernia group and the non-diaphragmatic hernia group in terms of age ( χ2=16.057, P<0.01), BMI ( χ2=16.057, P<0.01), and tumor location ( χ2=12.048, P=0.002). Multivariate logistic regression analysis revealed that age ≥65 years ( OR=1.236, P=0.023) and BMI<25 kg/m2 ( OR=0.810, P<0.01) were independent risk factors for the development of diaphragmatic hernia after MIME. Survival analysis showed no significant difference in long-term survival between patients with and without diaphragmatic hernia after MIME ( P=0.187), and whether patients with diaphragmatic hernia underwent surgery was not associated with long-term prognosis ( P=0.560). Conclusion:Patients with BMI<25 kg/m 2 and age ≥65 years are independent risk factors for diaphragmatic hernia after MIME. The occurrence of diaphragmatic hernia is not associated with prognosis, and whether patients with diaphragmatic hernia undergo surgery does not affect the prognosis.
3.Efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma
Huilai LYU ; Mingbo WANG ; Chunyue GAI ; Fan ZHANG ; Yonggang ZHU ; Yu LIU ; Jiachen LI ; Weilu DING ; Shi XU ; Zhenhua LI ; Bokang SUN ; Wenda GAO ; Ziqiang TIAN
Chinese Journal of Surgery 2025;63(11):1023-1030
Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.
4.Analysis of risk factors of diaphragmatic hernia after thoraco-laparoscopic minimally invasive McKeown esophagectomy
Zhenhua LI ; Weilu DING ; Huilai LYU ; Bokang SUN ; Keqin DONG ; Mingbo WANG ; Peng SU ; Ziqiang TIAN
Chinese Journal of Surgery 2025;63(2):130-135
Objective:To explore the related risk factors of diaphragmatic hernia after thoraco-laparoscopic minimally invasive Mckeown esophagectomy (MIME).Methods:This is a retrospective controlled study. A retrospective analysis was conducted on the clinical data of patients who underwent MIME at the Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, from January 2016 to December 2023. A total of 619 patients were included. There were 423 males and 196 females, aged (63.7±7.6) years (range: 37 to 87 years). The diagnosis of diaphragmatic hernia after MIME was made based on clinical symptoms and CT scans. Patients were divided into two groups: the diaphragmatic hernia group ( n=16) and the non-diaphragmatic hernia group ( n=603). Clinical data, including age, gender, body mass index (BMI), smoking history, tumor location (upper, middle, and lower thoracic esophagus), preoperative neoadjuvant therapy history, and tumor staging, were collected and analyzed. A BMI of 25 kg/m2 and age of 65 years were used as cutoff values. The χ2 test and Fisher′s exact test were used to compare the data between the two groups, and Logistic regression was employed for risk factor analysis. The diaphragmatic hernia group and non-diaphragmatic hernia group were matched in a 1∶3 ratio with a caliper value of 0.02 by propensity score matching. Kaplan-Meier method was used for survival analysis and compared using the log-rank test for between-group differences. Results:The proportion of patients with diaphragmatic hernia after MIME who underwent surgical treatment was 6/16. Statistically significant differences were observed between the diaphragmatic hernia group and the non-diaphragmatic hernia group in terms of age ( χ2=16.057, P<0.01), BMI ( χ2=16.057, P<0.01), and tumor location ( χ2=12.048, P=0.002). Multivariate logistic regression analysis revealed that age ≥65 years ( OR=1.236, P=0.023) and BMI<25 kg/m2 ( OR=0.810, P<0.01) were independent risk factors for the development of diaphragmatic hernia after MIME. Survival analysis showed no significant difference in long-term survival between patients with and without diaphragmatic hernia after MIME ( P=0.187), and whether patients with diaphragmatic hernia underwent surgery was not associated with long-term prognosis ( P=0.560). Conclusion:Patients with BMI<25 kg/m 2 and age ≥65 years are independent risk factors for diaphragmatic hernia after MIME. The occurrence of diaphragmatic hernia is not associated with prognosis, and whether patients with diaphragmatic hernia undergo surgery does not affect the prognosis.
5.Recent Advances and Hot Spots of Neoadjuvant Immunotherapy Combined with Chemotherapy for Esophageal Carcinoma
Huilai LYU ; Chunyue GAI ; Mingbo WANG ; Zhenhua LI ; Jiachen LI ; Shi XU ; Weilu DING ; Yu LIU ; Ziqiang TIAN
Cancer Research on Prevention and Treatment 2024;51(12):994-999
Surgery-based multidisciplinary comprehensive treatment is the preferred treatment strategy for local advanced esophageal cancer. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been recommended by the Chinese Society of Clinical Oncology (CSCO) guideline. With the advent of immunotherapy, neoadjuvant immunotherapy combined with chemotherapy has received much attention, and the first phase Ⅲ study has also confirmed that neoadjuvant immunotherapy combined chemotherapy is a promising treatment option. This article will review the recent advances and hot spots of neoadjuvant immunotherapy combined with chemotherapy.
6.Development of HIV infection risk assessment tool for men who have sex with men based on Delphi method
Lingling LI ; Zhen JIANG ; Weilu SONG ; Yingying DING ; Jie XU ; Na HE
Chinese Journal of Epidemiology 2017;38(10):1426-1430
Objective To develop a HIV infection risk assessment tool for men who have sex with men (MSM) based on Delphi method.Methods After an exhaustive literature review,we used Delphi method to determine the specific items and relative risk scores of the assessment tool through two rounds of specialist consultation and overall consideration of the opinions and suggestions of 17 specialists.Results The positivity coefficient through first and second round specialist consultation was 100.0% and 94.1%,respectively.The mean of authority coefficients (Cr) was 0.86.Kendall's W coefficient of the specialist consultation was 0.55 for the first round consultation (x2=84.426,P<0.001) and 0.46 for the second round consultation (x2=65.734,P<0.001),respectively,suggesting that the specialists had similar opinions.The final HIV infection risk assessment tool for MSM has 8 items.Conclusions The HIV infection risk assessment tool for MSM,developed under the Delphi method,can be used in the evaluation of HIV infection risk in MSM and individualized prevention and intervention.However,the reliability and validity of this risk assessment tool need to be further evaluated.
7.Tissue distribution and excretion of baicalein and its main metabolite in rats by LC-MS/MS
Wenyuan LIU ; Weilu XU ; Ping LI ; Feng FENG ; Li DING
Journal of China Pharmaceutical University 2009;40(4):348-352
Aim: To study the distribution and excretion of baicalein and baicalin in rats. Methods: An LC/MS method was applied. Chromatographic separation was performed on a C_(18) column( 150 mm ×6.0 mm, 5 μm) with methanol-10 mmol/L ammonium acetate (containing 0. 5% formic acid) as the mobile phase. A trip-quadrupole tandem mass spectrometer was set in positive selected reaction monitoring mode. The sample was extracted with methanol-acetonitrile( 1:1) after the addition of phosphoric buffer solution and luteolin, which acted as the internal standard. The supernatant was evaporated to dryness, and the residual was reconstituted with mobile phase and analyzed. Results: The distribution profiles of the parent drug and its main metabolite showed two peaks between 20-40 min and 8-10 h after oral administration of baicalein, which fit the plasma concentration-time profile of baicalein in rats. At 20 min after the dosing, the concentration levels of baicalein were significantly higher than those of baicalin in stomach, liver and intestines, the converse result occurred in kidney. The excretion results showed that baicalin was the predominant excretion form in bile and urine, while baicalein was the negligible excretion form. There was more baicalein than baicalin in rat feces. Conclusion: Baicalein was absorbed and distributed quickly to various tissues and easily transformed to its metabolite at the same time.

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