1.Plasma miRNA testing in the differential diagnosis of very early-stage hepatocellular carcinoma: a multicenter real-world study
Jie HU ; Ying XU ; Ao HUANG ; Lei YU ; Zheng WANG ; Xiaoying WANG ; Xinrong YANG ; Zhenbin DING ; Qinghai YE ; Yinghong SHI ; Shuangjian QIU ; Huichuan SUN ; Qiang GAO ; Jia FAN ; Jian ZHOU
Chinese Journal of Clinical Medicine 2025;32(3):350-354
Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP<20 ng/mL, DCP<40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P<0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P<0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.
2.Analysis of change trend of hepatectomy for 17 232 cases of hepatocellular carcinoma and efficacy of fluorescent laparoscopic hepatectomy: a 10-year single center study
Kai ZHU ; Qiang GAO ; Xiaoying WANG ; Zhenbin DING ; Yinghong SHI ; Qinghai YE ; Huichuan SUN ; Shuangjian QIU ; Jian ZHOU ; Jia FAN
Chinese Journal of Digestive Surgery 2025;24(4):507-514
Objective:To investigate the change trend of hepatectomy for hepatocellular carcinoma and efficacy of fluorescent laparoscopic hepatectomy in a single center from 2014?2023.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 17 232 patients of hepatocellular carcinoma who were admitted to Zhongshan Hospital of Fudan University from January 2014 to December 2023 were collected. There were 14 404 males and 2 828 females, aged 58(range, 11?94)years. Observation indicators: (1) change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014?2023; (2) propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy; (3) intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶3 nearest neighbor matching method, with the caliper value of 0.01. Results:(1) Change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014-2023. Among 17 232 patients of hepatocellular carcinoma, 4 074 cases underwent laparoscopic surgery, and 13 158 cases underwent open surgery or conversion from laparoscopic to open surgery. From 2014 to 2023, the proportions of laparos-copic surgery in hepatectomy were 8.993%(117/1 301), 6.804%(99/1 455), 9.379%(145/1 546), 17.511%(287/1 639), 23.828%(427/1 792), 24.572%(459/1 868), 29.662%(544/1 834), 31.568%(584/1 850), 38.080%(599/1 573), and 34.246%(813/2 374), respectively. The proportions of Grade Ⅲ surgery in laparoscopic hepatectomy were 11.966%(14/117), 7.071%(7/99), 12.414%(18/145), 21.254%(61/287), 28.337%(121/427), 27.887%(128/459), 34.375%(187/544), 34.644%(214/584), 35.726%(214/599), and 42.681%(347/813), respectively. From 2016 to 2023, the proportions of the application of fluorescent laparoscopy in laparoscopic hepatectomy were 2.069%(3/145), 5.923%(17/287), 8.431%(36/427), 10.022%(46/459), 17.647%(96/544), 24.829%(145/584), 9.182%(55/599), and 12.915%(105/813), respectively. (2) Propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy. Among the 4 074 patients who underwent laparoscopic liver resection, 503 cases using fluorescent laparoscopy were assigned to the fluorescent laparoscopy group, 3 571 cases using conventional laparoscopy were assigned to the conventional laparoscopy group. A total of 1 794 patients were successfully matched, with 483 cases in the fluorescent laparoscopy group and 1 311 cases in the conventional laparoscopy group. After propensity score matching, the confounding biases of the maximum tumor diameter and the year of surgery were eliminated, and the two groups were comparable. (3) Intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. After propensity score matching, there was no perioperative death in either the fluorescent laparoscopy group or the conventional laparoscopy group.The operation time of patients in the fluorescent laparoscopy group was 240(150,328)minutes, the portal triad clamping time was 30(15,45)minutes, the volume of intraoperative blood loss was 50(30,100)mL, the number of patients with complication 72, respectively. For patients in the conventional laparoscopy group, the above indicators were 180(131,240)minutes, 23(15,30)minutes, 55(50,100)mL, and 248, respectively. There were significant differences in the above indicators between the two groups ( Z=?7.593, ?7.372, ?4.941, χ2=3.873, P<0.05). Conclusion:The proportion and difficulty level of laparoscopic hepatectomy for hepatocellular carcinoma in Zhongshan Hospital of Fudan University have shown an upward trend during 2014?2023. Compared with conventional laparoscopy, patients undergoing fluorescent laparoscopic hepatectomy have longer operation time and portal triad clamping time, but less intraoperative blood loss and lower iproportion of complications.
3.Analysis of change trend of hepatectomy for 17 232 cases of hepatocellular carcinoma and efficacy of fluorescent laparoscopic hepatectomy: a 10-year single center study
Kai ZHU ; Qiang GAO ; Xiaoying WANG ; Zhenbin DING ; Yinghong SHI ; Qinghai YE ; Huichuan SUN ; Shuangjian QIU ; Jian ZHOU ; Jia FAN
Chinese Journal of Digestive Surgery 2025;24(4):507-514
Objective:To investigate the change trend of hepatectomy for hepatocellular carcinoma and efficacy of fluorescent laparoscopic hepatectomy in a single center from 2014?2023.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 17 232 patients of hepatocellular carcinoma who were admitted to Zhongshan Hospital of Fudan University from January 2014 to December 2023 were collected. There were 14 404 males and 2 828 females, aged 58(range, 11?94)years. Observation indicators: (1) change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014?2023; (2) propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy; (3) intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶3 nearest neighbor matching method, with the caliper value of 0.01. Results:(1) Change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014-2023. Among 17 232 patients of hepatocellular carcinoma, 4 074 cases underwent laparoscopic surgery, and 13 158 cases underwent open surgery or conversion from laparoscopic to open surgery. From 2014 to 2023, the proportions of laparos-copic surgery in hepatectomy were 8.993%(117/1 301), 6.804%(99/1 455), 9.379%(145/1 546), 17.511%(287/1 639), 23.828%(427/1 792), 24.572%(459/1 868), 29.662%(544/1 834), 31.568%(584/1 850), 38.080%(599/1 573), and 34.246%(813/2 374), respectively. The proportions of Grade Ⅲ surgery in laparoscopic hepatectomy were 11.966%(14/117), 7.071%(7/99), 12.414%(18/145), 21.254%(61/287), 28.337%(121/427), 27.887%(128/459), 34.375%(187/544), 34.644%(214/584), 35.726%(214/599), and 42.681%(347/813), respectively. From 2016 to 2023, the proportions of the application of fluorescent laparoscopy in laparoscopic hepatectomy were 2.069%(3/145), 5.923%(17/287), 8.431%(36/427), 10.022%(46/459), 17.647%(96/544), 24.829%(145/584), 9.182%(55/599), and 12.915%(105/813), respectively. (2) Propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy. Among the 4 074 patients who underwent laparoscopic liver resection, 503 cases using fluorescent laparoscopy were assigned to the fluorescent laparoscopy group, 3 571 cases using conventional laparoscopy were assigned to the conventional laparoscopy group. A total of 1 794 patients were successfully matched, with 483 cases in the fluorescent laparoscopy group and 1 311 cases in the conventional laparoscopy group. After propensity score matching, the confounding biases of the maximum tumor diameter and the year of surgery were eliminated, and the two groups were comparable. (3) Intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. After propensity score matching, there was no perioperative death in either the fluorescent laparoscopy group or the conventional laparoscopy group.The operation time of patients in the fluorescent laparoscopy group was 240(150,328)minutes, the portal triad clamping time was 30(15,45)minutes, the volume of intraoperative blood loss was 50(30,100)mL, the number of patients with complication 72, respectively. For patients in the conventional laparoscopy group, the above indicators were 180(131,240)minutes, 23(15,30)minutes, 55(50,100)mL, and 248, respectively. There were significant differences in the above indicators between the two groups ( Z=?7.593, ?7.372, ?4.941, χ2=3.873, P<0.05). Conclusion:The proportion and difficulty level of laparoscopic hepatectomy for hepatocellular carcinoma in Zhongshan Hospital of Fudan University have shown an upward trend during 2014?2023. Compared with conventional laparoscopy, patients undergoing fluorescent laparoscopic hepatectomy have longer operation time and portal triad clamping time, but less intraoperative blood loss and lower iproportion of complications.
4.Pathological features of immune-mediated hepatitis due to immune checkpoint inhibitors and anti-angiogenesis targeted therapy
Qiongyan ZHANG ; Lingli CHEN ; Feng GAO ; Akesu SUJIE ; Yingyong HOU ; Xiaowu HUANG ; Cheng HUANG ; Huichuan SUN ; Jian ZHOU ; Yuan JI
Chinese Journal of Pathology 2020;49(4):329-335
Objective:To compare the histologic features of immune-mediated hepatitis (IMH) due to immune checkpoint inhibitors (ICIs) monotherapy and combined ICIs anti-angiogenesis tyrosine kinases (TKIs) targeted therapy.Methods:Twenty-one IMH patients who had liver biopsy during ICIs treatment in Zhongshan Hospital of Fudan University from 2015 to 2019 were included. Among them, ten were treated with ICIs monotherapy, and 11 were treated with combined ICIs and anti-angiogenesis targeted therapy. The histologic features of IMH were assessed by HE staining and PD-L1/2 was evaluated by immunohistochemical staining.Results:Patients treated with monotherapy ICIs presented with different levels of lobular hepatitis and portal inflammation. Besides, there were also cholangitis, endothelialitis, Kupffer cells activation and peliosisi hepatitis. Eight cases (8/10) showed mild and two cases (2/10) showed moderate hepatic injury. As for patients receiving combined ICIs and TKIs therapy, the extent of IMH was more severe, with four cases (4/11) showing moderate-severe liver injury, with confluent or bridging necrosis, portal inflammation, cholangitis, interface hepatitis. Among these, one patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. In those cases with severe liver injury, many CD8 positive lymphocytes aggregated in the portal area and hepatic sinusoid, and PD-L1 was expressed in many endothelial cells. There were both 2 cases of death in ICIs monotherapy and combination therapy group. Among the latter group, 1 patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction.Conclusion:Compared with ICIs monotherapy, combined ICIs and anti-angiogenesis targeted TKIs therapy may cause overlapping hepatic injury, leading to severe IMH.
5.Anatomical Lobectomy and Pneumonectomy by Video-Assisted Thoracoscopic Surgery
Chengguo FU ; Jie JIANG ; Huichuan GAO
Chinese Journal of Minimally Invasive Surgery 2001;0(03):-
Objective To evaluate the feasibility of video-assisted minimal access surgery for lobectomy and pneumonectomy. Methods Under general anesthesia, via a video-assisted minimal access approach, anatomical lobectomy or pneumonectomy was performed through a 6- to 8-cm incision. A total of 42 patients, including 33 patients with lung cancer and 9 with benign tumor, received lobectomy (39 cases) or pneumonectomy (3 cases), which were performed under a video vision and a direct vision through the small incision. Results The average operation time was 2.5 h (1.5-4.5 h),and average blood loss was 200 ml (100-500 ml). In one patient, the incision was extended to a length of 12 cm because of tight adhesion between the tumor and the arch of azygos vein. Traditional open surgery was performed on one patient owning to the injury of the pulmonary artery trunk, which was due to the tight adhesion between the lung cancer at the left upper lobe and the pulmonary artery. Eight days after lobectomy, a 72-year-old patient with lung cancer died of respiratory failure caused by infection of the lungs. No operation-related complications occurred in the other 41 patients during a 6- to 47-month follow-up (mean, 18). Among the 32 patients with lung cancer, who were followed up for 8-47 months, 3 died of liver and bilateral lungs metastasis 8, 11, or 17 months after the opearation. Conclusion Video-assisted minimal access surgery is feasible for lobectomy and pneumonectomy.

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