1.Long-term efficacy of sequential surgery after immune combined with targeted therapy for initially unresectable hepatocellular carcinoma
Xuerui LI ; Junfeng LI ; Wenwen ZHANG ; Zhijun WANG ; Bingyang HU ; Haowen TANG ; Bing LIU ; Tao WAN ; Zhe LIU ; Zhanbo WANG ; Shichun LU
Chinese Journal of Hepatobiliary Surgery 2024;30(1):9-14
Objective:To assess the long-term outcome of sequential radical surgery after immune combined with targeted therapy for patients with initially unresectable hepatocellular carcinoma (HCC).Methods:Clinical data of 100 patients with initially unresectable HCC undergoing sequential radical surgery after immune combined with targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital from December 2018 to August 2023 were prospectively collected, including 87 males and 13 females, with a median age of 55 (24-73) years. The pre-treatment tumor staging was determined using the China liver cancer staging (CNLC). The efficacy of immune combined with targeted therapy was accessed using the modified response evaluation criteria in solid tumor (mRECIST). The cycles of immune combined with targeted therapy were analyzed. The tumor residual of resected tissue was analyzed through a standard pathological protocol. The prognosis was analyzed using the Kaplan-Meier method.Results:Upon initial diagnosis, there were 46 cases (46.0%) staged CNLC-Ⅲa and 40 (40.0%) staged CNLC-Ⅲb. There were also 14 cases (14.0%) staged CNLC-Ⅰb, Ⅱa, and Ⅱb who underwent immune combined with targeted therapy due to rupture of tumor or insufficient liver remnant. All patients received a median of 5 (3-28) cycles of immune combined with targeted therapy and underwent radical surgery after successful conversion. According to mRECIST, 14 (14.0%) were determined as complete remission, 63 (63.0%) as partial remission, 18 (18.0%) as stable disease, and 5 (5.0%) as disease progression. Of 24 (24.0%) were defined as pathologically complete remission by postoperative pathology. Furthermore, pathological tumor residue was less than 10% in 61 (61.0%) cases and less than 50% in 82 (82.0%) cases. The 1, 3, and 5 year-overall survival rates of patients were 98.0%, 83.1%, and 74.5%, respectively. The 1, 2 and 3 year-recurrence-free survival rates were 67.5%, 54.8%, and 49.6%, respectively.Conclusion:Sequential radical surgery after immune combined with targeted therapy benefits the long-term survival of patients with initially unresectable HCC.
2.A retrospective study of postoperative adjuvant therapy following immunotherapy combined with targeted therapy and sequential curative surgical procedures for initially unresectable hepatocellular carcinoma
Zikun RAN ; Haowen TANG ; Yinbiao CAO ; Wenwen ZHANG ; Zhe LIU ; Tao WAN ; Xuerui LI ; Junfeng LI ; Tianyu JIAO ; Shichun LU
Chinese Journal of Surgery 2024;62(6):543-548
Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.
3.A retrospective study of postoperative adjuvant therapy following immunotherapy combined with targeted therapy and sequential curative surgical procedures for initially unresectable hepatocellular carcinoma
Zikun RAN ; Haowen TANG ; Yinbiao CAO ; Wenwen ZHANG ; Zhe LIU ; Tao WAN ; Xuerui LI ; Junfeng LI ; Tianyu JIAO ; Shichun LU
Chinese Journal of Surgery 2024;62(6):543-548
Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.
4.Clinical efficacy of sequential surgery after immune and targeted therapy in downstaging initially unresectable hepatocellular carcinoma
Xuerui LI ; Wenwen ZHANG ; Bingyang HU ; Tao WAN ; Zhe LIU ; Haowen TANG ; Junfeng LI ; Yinbiao CAO ; Ze ZHANG ; Zhanbo WANG ; Shichun LU
Chinese Journal of Hepatobiliary Surgery 2023;29(1):15-21
Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.
5.Serum alpha-fetoprotein in predicting survival of patients with BCLC C hepatocellular carcinoma treated by salvage surgery after downstaging therapy
Yinbiao CAO ; Junfeng LI ; Haowen TANG ; Tao WAN ; Zhe LIU ; Bingyang HU ; Hao JIANG ; Shichun LU
Chinese Journal of Hepatobiliary Surgery 2023;29(1):22-27
Objective:To analyze the value of alpha-fetoprotein(AFP) in predicting survival of patients who underwent salvage surgery after tumor downstaging therapy in patients with advanced hepatocellular carcinoma.Methods:The data of 50 patients with Barcelona Clinic Liver Cancer Staging (BCLC) C hepatocellular carcinoma treated at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from December 2018 to December 2021 were collected. There were 45 males and 5 females, with the age of (53.0±10.5) years. The patients were divided into two groups based on the serum AFP level after tumor downstaging therapy, AFP normal group ( n=27, AFP≤20 μg/L) and the control group ( n=23, AFP>20 μg/L). Patient survival and tumor recurrence were followed up by outpatient review or telephone follow-up. The survival rate was calculated by the Kaplan-Meier method and compared by the log-rank test. The efficacy of combined immunotargeted therapy were compared between the two groups. Univariate and multivariate Cox regression analysis were carried to analyse the factors influcing prognosis. Results:The median survival time was not reached in both groups. The 1-year and 2-year cumulative survival rates were 95.0% and 88.2% in the normal group and 73.4% and 54.1% in the control group, respectively. The median relapse-free survival time of the normal group was not reached, and the median relapse-free survival time of the control group was 11 months. The 1-year recurrence-free survival rate was 78.1% in the normal group and 39.5% in the control group. The cumulative survival rate and relapse-free survival rate in the normal group were significantly higher than those in the control group (χ 2=7.60, 8.83, P=0.006, 0.003). The complete response, partial response and pathological complete response of tumors in the normal group were significant better than those in the control group. Multivariate Cox regression analysis showed that patients with serum AFP >20 μg/L ( HR=2.952, 95% CI: 1.023-8.517, P=0.045) after immunotherapy combined with targeted therapy had an increased risk of postoperative recurrence. Conclusion:The reduction of serum AFP to normal after downstaging therapy could be used as a prognostic indicator of salvage surgical in patients with BCLC C hepatocellular carcinoma, and AFP was related to the efficacy of downstaging therapy in patients.
6.Safety and efficacy of a treatment protocol in converting initially unresectable to resectable hepatocellular carcinoma
Ze ZHANG ; Yinbiao CAO ; Tao WAN ; Wenwen ZHANG ; Zhanbo WANG ; Junning CAO ; Bingyang HU ; Jun HAN ; Haowen TANG ; Liru PAN ; Shichun LU
Chinese Journal of Hepatobiliary Surgery 2022;28(1):15-20
Objective:To study the safety and efficacy of a treatment protocol using immune checkpoint inhibitors (ICIs) and antiangiogenic targeted drugs (AATDs) in converting 41 patients with initially unresectable to resectable hepatocellular carcinoma (HCC).Methods:The data of 41 patients with initially unresectable HCC treated with immunotherapy combined with targeted therapy from December 2018 to April 2021 in Chinese PLA General Hospital were analysed. There were 34 males and 7 females, aged (51.8±10.7) years. The clinical characteristics, conversion to resectable HCC, adverse drug reactions, surgical data and postoperative complications were analysed. Patients were followed-up by outpatients clinics or telephone calls.Results:There were 5 patients with Chinese Liver Cancer Staging (CNLC)-Ⅰb, 4 with CNLC-Ⅱ, 28 with CNLC-Ⅲa and 4 with CNLC-Ⅲb before the treatment protocol. Among them, 28 patients had portal vein tumor thrombosis (PVTT) and 4 had retroperitoneal lymph node metastases. All patients had a mean tumor diameter of (9.16±4.43) cm before and (6.49±4.69) cm after the treatment protocol. The latter was based on the last assessment before hepatectomy. The efficacy of the treatment protocol in converting unresectable to resectable HCC was assessed by the modified Response Evaluation Criteria in Solid Tumors after 3-15 cycles (median dose cycles, 5) of protocal therapy: 15 patients achieved a complete response; 15 patients achieved a partial response; 6 patients had a stable disease, and 5 patients had a progressive disease. 21 patients (51.2%) experienced adverse reactions associated with drug treatment, which resolved with symptomatic treatment or brief discontinuation of the therapy. All patients underwent successful hepatectomy. Postoperative complications of grade Ⅱ or higher occurred in 9 patients (22.0%). The cumulative overall survival rates at 6 months, 1 year and 2 years from diagnosis were 100.0%, 92.6% and 64.7% respectively. The cumulative overall survival rates at 6 months, 1 year and 2 years after surgery were 95.1%, 74.7% and 60.8%, and the recurrence-free survival rates at 6 months, 1 year and 2 years after surgery were 87.8%, 56.7% and 48.6%, respectively.Conclusions:This study provided preliminary evidences that surgical resection after immunotherapy combined with targeted therapy in patients with initially unresectable HCC was safe and efficacious.
7.Analysis of the risk factors related to prolonged drainage time in patients with selective abdominal drainage after laparoscopic cholecystectomy
Xinlan GE ; Haowen TANG ; Junning CAO ; Ke PAN ; Chonghui LI ; Bo LIU
Chinese Journal of Hepatobiliary Surgery 2022;28(4):280-283
Objective:To determine the risk factors of drainage time longer than 1 day in patients with selective abdominal drainage after laparoscopic cholecystectomy.Methods:The clinical data related to patients with selective abdominal drainage undergoing laparoscopic cholecystectomy from November 2009 to November 2019 at Chinese PLA General Hospital were retrospectively analyzed. Of 233 patients enrolled into this study, there were 147 males and 86 females, with a median aged 59.0 (47.5, 65.5) years old. The patients were divided into drainage time 1 day group of 65 patients and longer than 1 day group of 168 patients according to postoperative drainage time. The baseline data and perioperative data were collected, the risk factors correlated with drainage time longer than 1 day were analyzed.Results:The drainage time was 1 in the 1 day group and 2~8 in another group. Among the 233 patients, there was one with biliary leakage and 14 patients had abdominal bleeding, all of them healed after 2~3 days. All of the 233 patients were recovered when discharged. Independent risk factors related to drainage time longer than 1 day include BMI≥28 kg/m 2 ( OR=3.443, 95% CI: 1.411-8.405, P=0.007), operation time ≥65 min ( OR=2.570, 95% CI: 1.310-5.045, P=0.006), thickness of gallbladder wall ≥0.5 cm ( OR=12.720, 95% CI: 1.350-5.478, P=0.005), postoperative stomachache ( OR=13.537, 95% CI: 1.685-108.748, P=0.014) and postoperative fever ( OR=8.156, 95% CI: 1.035-64.249, P=0.046). Conclusion:For patients undergoing selective abdominal drainage after laparoscopic cholecystectomy with BMI ≥28 kg/m 2, operation time ≥65 min, gallbladder wall thickness ≥0.5 cm, postoperative abdominal pain and fever, clinicians should appropriately prolong the drainage time to ensure medical safety.
8.Progress on the correlation between peripheral blood inflammatory index and the prognosis of pancreatic cancer
Hongyue YANG ; Yanzhang TIAN ; Shaojian MO ; Lingbo HUO ; Haowen TANG
Chinese Journal of Hepatobiliary Surgery 2022;28(4):310-313
Globally, the incidence of pancreatic cancer is on a rise. Pancreatic cancer is characterized by difficulty in early diagnosis, frequent distant metastasis, low surgical resection rate, and high risk of postoperative recurrence. Better treatments need to be developed to prolong the prognosis. Studies have confirmed that inflammation is closely correlated with tumorigenesis, and inflammatory mediators play important roles on tumor microenvironment of pancreatic cancer and lead to poor prognosis. This article reviewed the progress on the correlation between peripheral blood inflammatory index and the prognosis of pancreatic cancer.
9.Current situation and risk factors analysis for hypoalbuminemia of maintenance hemodialysis patients: a multiple centers experience
Xingming TANG ; Haowen ZHONG ; Jieping HU ; Huizhao DENG
Chinese Journal of Postgraduates of Medicine 2021;44(5):411-415
Objective:To evaluate the risk factors of hypoalbuminemia (serum albumin <35 g/L) in the maintenance hemodialysis (MHD) patients.Methods:From January 2011 to December 2018, 915 patients (≥18 years) who underwent MHD programs from 12 hospitals in south China were enrolled in a retrospective analysis. Univariate and multivariate Logistic regression analysis was applied to evaluate the risk factors of hypoalbuminemia in the MHD patients.Results:The MHD patients had poor albumin level in general, with hypoalbuminemia accounting for about 20.55% (188/915). Compared with the patients with normal albumin level, the patients with hypoalbuminemia had older age (61.46 years vs. 55.85 years, P<0.01), the greater incidence of diabetes [29.79%(56/188) vs. 19.39%(141/727), P = 0.002] and the lower application in high flux dialysis [42.55%(80/188) vs. 57.36%(417/727), P<0.01], while the gender, duration of dialysis, dialysis frequencies and the incidence of hepatitis showed no significant difference between 2 groups. In linear correlation analysis, albumin and hemoglobin level were positively correlated ( r = 0.213, P<0.01). In Spearmen correlation analysis, albumin was negatively correlated with age, hypersensitive C reactive protein (hsCRP), alkaline phosphatase, and diabetes ( r = -0.232, -0.176, -0.153 and -0.132; P<0.01); and it was positively correlated with the Kt/V and the application in high flux dialysis ( r = 0.151 and 0.124, P<0.01). The multivariate Logistic regression analysis showed that age, diabetes, alkaline phosphatase and hsCRP were the independent risk factors of hypoalbuminemia, while the application of high flux dialysis and hemoglobin were the independent protection factors. Conclusions:The patients undergoing a MHD program have poor albumin level. Diabetes is the independent risk factor of hypoalbuminemia of MHD patients, and the practice of high flux dialysis may reduce the hypoalbuminemia.
10.Clinical value of preoperative perfluorobutane contrast-enhanced ultrasound in the evaluation of microvascular invasion and recurrence of hepatocellular carcinoma
Bo JIANG ; Xiang FEI ; Xiaowei FAN ; Ming SU ; Bin LIANG ; Bingyang HU ; Tao WAN ; Haowen TANG ; Wenwen ZHANG ; Fang LI ; Shichun LU ; Yukun LUO
Chinese Journal of Hepatobiliary Surgery 2021;27(12):894-899
Objective:To study the use of perfluorobutane contrast-enhanced ultrasound (CEUS) in preoperative detection of microvascular invasion (MVI), and postoperative short-term recurrence of hepatocellular carcinoma (HCC).Methods:Patients who underwent hepatectomy with curative intent at the Chinese PLA General Hospital from January 2021 to April 2021 were prospectively enrolled into this study. Of 42 patients in this study, there were 36 males and 6 females, with age of (56.51±11.95) years old. All patients underwent preoperative perfluorobutane CEUS, and the characteristics of ultrasound, the vascular phase and Kupffer phase of perfluorobutane CEUS were recorded. Based on the pathological results, these patients were divided into the MVI and non-MVI groups. These patients underwent liver MRI once every 3 months postoperatively to diagnose tumor recurrence. According to the recurrence of HCC 6 months after operation, these patients were divided into the non-recurrence and the recurrence groups. Independent risk factors for MVI and short-term recurrence were analyzed by univariate and multivariate analyses.Results:Two patients had two lesions, and the remaining 40 patients had a single lesion. The pathological diagnosis of all the lesions were HCC (14 patients in the MVI group and 28 patients in the non-MVI group). The median follow-up was 6 (3, 6) months, and there were 8 patients in the recurrence group and 34 patients in the non-recurrence group. On logistic analysis, independent risk factors for MVI included the number of vessels detected on color Doppler flow imaging (CDFI) ( OR=5.762, 95% CI: 1.597-20.785, P=0.007), increased tumor size by more than 10% after CEUS arterial enhancement ( OR=10.186, 95% CI: 3.647-28.447, P=0.037), and thickness of corona enhancement at Kupffer phase of greater than 5 mm ( OR=17.340, 95% CI: 6.124-49.095, P=0.040). Cox regression showed the independent risk factors for short-term recurrence to include the number of vessels in CDFI ( RR=7.519, 95% CI: 1.086-52.051, P=0.041) and thickness of corona enhancement at Kupffer phase of greater than 5 mm ( RR=10.623, 95% CI: 1.265-89.218, P=0.030). Conclusion:Preoperative perfluorobutane CEUS had potential values in detecting MVI and in predicting postoperative short-term recurrence of HCC.

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