Volume 31,Issue 7,2022 Table of Contents

1 Hunan expert consensus on clinical pathway for enhanced recovery after surgery of hepatopancreatobiliary surgical diseases (2022 version)

2022, 31(7):847-859. DOI: 10.7659/j.issn.1005-6947.2022.07.001

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Although the concept of enhanced recovery after surgery (ERAS) has been rapidly acknowledged and widely used in China, it has encountered a series of practical problems in clinical application. Therefore, it is particularly necessary to carry out research on the ERAS clinical pathway for hepatopancreatobiliary surgical diseases according to the specific situations of hospitals at all levels in Hunan province. The Medical Administration Division of Hunan Provincial Health Commission, the Hepatobiliary Surgery Professional Committee of Hunan Medical Association, the Professional Committee of Enhanced Recovery After Surgery of Hunan Health Management Association, the Hepatobiliary Surgery Professional Committee of Hunan International Medical Exchange and Promotion Association, and the Hunan Alliance of Hepatobiliary and Pancreatic Surgery organized relevant experts in Hunan province to jointly discuss and developed the guiding principles for the clinical application of ERAS concept, and the data collection and case inclusion criteria of ERAS clinical pathway for hepatopancreatobiliary surgical diseases, and put forward the expert consensus on the clinical pathway for hepatopancreatobiliary surgical diseases in accordance with the actual situation in Hunan province, which provides reference and guidance for further promoting the implementation and application of ERAS concept normatively and orderly in the clinical practice of hepatopancreatobiliary surgery in Hunan province.

2 A systematic review and Meta-analysis of hepatic arterial infusion chemotherapy versus transarterial chemoembolization/embolization for unresectable hepatocellular carcinoma

ZHAO Yi , CHENG Sheng , WANG Yongchen , HUANG Ping

2022, 31(7):860-869. DOI: 10.7659/j.issn.1005-6947.2022.07.002

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Background and Aims Hepatocellular carcinoma (HCC) is one of the common malignant tumors. Transarterial chemoembolization (TACE) and transarterial embolization (TAE) are common treatment options for unresectable HCC. In recent years, hepatic arterial infusion chemotherapy (HAIC) has been used to treat advanced HCC and has achieved satisfactory therapeutic effects. However, few studies directly compare HAIC with TACE/TAE. Therefore, this study was conducted to evaluate the efficacy and safety of HAIC and TACE/TAE in the treatment of unresectable HCC.Methods The studies on HAIC and TACE/TAE in the treatment of unresectable HCC published as of 14 August 2021 were searched in PubMed, OvidSP, Cochrane Library, Web of Science, Wanfang Database, CNKI, and VIP Chinese Journal Database. The data relevant to the outcome variables such as overall survival (OS), disease-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse events were extracted, and Meta-analysis was performed using Review Manager 5.4 software.Results A total of 5 studies were finally included. Results of Meta-analysis showed that HAIC group was superior to TACE/TAE group in terms of OS (HR=0.39, 95% CI=0.18-0.86, P=0.02), ORR (RR=3.82, 95% CI=2.41-6.04, P<0.000 01) and DCR (RR=1.52, 95% CI=1.12-2.05, P=0.006). Moreover, the results were still consistent after exclusion of possible sources of heterogeneity by sensitivity analysis. There was no significant difference between HAIC group and TACE/TAE group in PFS (HR=0.34, 95% CI=0.11-1.04, P=0.06), but the PFS in HAIC group was better than that in TACE/TAE group after exclusion of possible sources of heterogeneity (HR=0.56, 95% CI=0.43-0.73, P<0.000 1). For any grade of adverse events, the risk ratios of thrombocytopenia (RR=1.59, 95% CI=1.04-2.44, P=0.03) and diarrhea (RR=4.57, 95% CI=2.01-10.37, P=0.003) were higher, while the risk ratios of elevation of alanine aminotransferase (RR=0.57, 95% CI=0.35-0.92, P=0.02) and hyperbilirubinemia (RR=0.37, 95% CI=0.26-0.53, P<0.000 01) were lower in HAIC group than those in TACE/TAE group; for grade 3-4 adverse events, the risk of leukopenia in HAIC group was higher than that in TACE/TAE group (RR=6.32, 95% CI=1.71-23.28, P=0.006); for either grade 3-4 adverse events or any grade, the risk of fever in the HAIC group was lower than that in the TACE/TAE group (P<0.05); there were no significant differences in incidence rates of anemia, neutropenia, and hypoproteinemia as well as abdominal pain and vomiting between the two groups (all P>0.05).Conclusion Compared with TACE/TAE, HAIC offers better tumor response and longer survival, and acceptable adverse reactions. So, it is a better treatment option for patients with unresectable HCC.

3 Experience in surgical treatment of resectable hepatocellular carcinoma complicated with portal vein carcinoma thrombus

LI Liuzheng , ZHANG Shirong , LU Shun , LI Bo , ZHAO Hairong , AO Qiang , GAO Xuechang , Gong Guocha , FENG Jiawei , XU Leisheng , WANG Xue

2022, 31(7):870-879. DOI: 10.7659/j.issn.1005-6947.2022.07.003

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Background and Aims For patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT), the surgical resection rate is low and the recurrence rate is high, resulting in poor prognosis. Its treatment method is still controversial. In this paper, the authors summarize the experience of surgical treatment of resectable HCC combined with PVTT, and compare the short- and long-term efficacy of surgery and transcatheter arterial chemoembolization (TACE) for these patients.Methods The clinical data of 39 patients with resectable HCC and concomitant PVTT treated from March 2016 to March 2021 were retrospectively analyzed. Of the patients, 23 cases underwent surgical treatment (surgery group) and 16 patients were treated with TACE (TACE group). The main clinical variables and prognosis were compared between the two groups of patients, and the influencing factors for the prognosis of patients were analyzed.Results In surgery group, except one patient who had extensive tumor invasion and only underwent tissue sample removal for biopsy, surgery was completed in all the remaining patients, without surgical death; 19 patients had negative surgical margins; 2 patients developed postoperative liver failure, and were cured and discharged after treatment with artificial liver support and supportive measures. In TACE group, the super-selection, perfusion and embolization of the hepatic arteries were uneventfully performed in all the 16 patients; 1 patient died of acute liver failure 3 d after TACE due to the complete embolization of the hepatic artery. In surgery group, 8 underwent adjuvant TACE after operation and 5 patients received targeted therapy, one of whom with type I PVTT still survived for 47 months after postoperative treatment such as TACE. In TACE group, 13 patients underwent repeated treatment and 4 patients received targeted therapy, one of whom with type II PVTT undergoing 7 times of interventional perfusion chemotherapy and embolization still survived for 25 months. In surgery group compared with TACE group, the operative time was prolonged, the medical cost was increased, the number of cases undergoing postoperative TACE was decreased, and the numbers of cases without any other postoperative treatment and cases whose postoperative AFP level returned to normal were increased (all P<0.05). The median survival time was 16.2 months for surgery group and 9.5 months for TACE group, and the 0.5-, 1-, 2- and 3-year survival rates were 65.2%, 43.5%, 34.8% and 17.4% for surgery group, and 46.7%, 33.3.0%, 13.3% and 0 for TACE group, respectively. There were significant differences in median survival time and accumulate survival rate between the two groups (both P<0.05). Results of univariate analysis showed that PVTT classification, AFP level, tumor size, tumor number were related to postoperative survival time of patients (all P<0.05). Results of multivariate analysis revealed that treatment mode, PVTT classification, tumor diameter and AFP level were independent influencing factors for postoperative survival time (all P<0.05).Conclusion PVTT classification, tumor diameter and AFP level can directly affect the survival of patients with HCC and PVTT. The efficacy of surgical resection is significantly better than that of TACE, especially for those with resectable HCC and type I/II PVTT. However, the treatment choice may be limited by the patient's will and economic factors.

4 Application value of intraoperative Sonazoid-enhanced ultrasonography in laparoscopic microwave ablation of hepatocellular carcinoma in special locations

DUAN Wenbin , XUE Rong , WANG Zicheng , YANG Jianhui , MAO Xianhai

2022, 31(7):880-889. DOI: 10.7659/j.issn.1005-6947.2022.07.004

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Background and Aims Microwave ablation (MWA) for the treatment of hepatocellular carcinoma (HCC) is often performed under ultrasound guidance. MWA in some cases can be completed via a percutaneous approach, while a laparoscopic approach is usually chosen for HCC in special locations. However, laparoscopic MWA also has limitations. For small HCC, isoechoic nodules or target lesions within a cirrhotic background, gray-scale ultrasound (GSUS) is sometimes difficult to locate the target lesions. At this time, contrast-enhanced ultrasound can be used to increase the contrast between the lesions and the liver parenchyma and improve the visibility of the target lesions. However, the time window of enhancement imaging with commonly used contrast agents such as SonoVue is relatively short, so its guiding role in HCC ablation is limited. Sonazoid was approved for use in China in 2019. Compared with other contrast agents, the advantage of Sonazoid is that it can be phagocytosed by Kupffer cells in the liver and has its unique Kupffer phase about 10 min after the injection of contrast agent. At this stage, the ultrasonic imaging of liver parenchyma is enhanced, and previous literature has reported that that Kupffer phase can last for at least 1 h. Meanwhile HCC exhibits low enhancement or no enhancement due to the lack of Kupffer cells. Therefore, intraoperative contrast enhanced ultrasound with Sonazoid (S-CEUS) is theoretically helpful for the localization of the target lesions, and can provide a sufficient time window for MWA. This study was performed to investigate the advantages of S-CEUS in tumor localization compared with GSUS in laparoscopic MWA for HCC in special locations, and analyzed the real-time guiding capability of S-CEUS for ablation.Methods From June 2020 to December 2021, 49 HCC patients undergoing laparoscopic MWA with target lesions located in special areas in Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital/the First Affiliated Hospital of Hunan Normal University were consecutively selected. GSUS and S-CEUS were respectively performed during laparoscopic MWA. The positioning accuracy of the target lesions was analyzed. The 5-point confidence scale was used to evaluate the visibility of the target lesion and the difference of the visibility of the target lesions between GSUS and S-CEUS was compared. At the same time, the duration of Kupffer phase was observed, and the efficacy of MWA performed in this phase was evaluated.Results In the 49 patients, 56 lesions were found by preoperative MRI examination, and 59 lesions were detected by S-CEUS during operation, which were all identified as HCC by aspiration biopsy. The visibility score of target lesions was 2.86±0.96 for GSUS, and was 3.90±0.78 in arterial phase and 4.25±0.60 in Kupffer phase for S-CEUS. The visibility scores of target lesions in both arterial phase and Kupffer phase were better than that in GSUS (both P<0.001), and the visibility score of target lesions in Kupffer phase is better than that in arterial phase (P<0.001). The Kupffer phase lasted more than 1 h; the localization of all lesions in patients with multiple lesions known before operation was completed by injection of the contrast agent in one session; three occult tumors that were not found by preoperative imaging examination were all found in Kupffer phase; all lesions underwent MWA in Kupffer phase. Both immediate evaluation by Sonazoid injection again 15 min after ablation and enhanced MRI examination one month after operation showed that all lesions were ablated completely.Conclusion For laparoscopic MWA of HCC in special locations, the visibilities of target lesions in arterial phase and Kupffer phase of S-CEUS are better than that of GSUS, which is helpful for the localization of target lesions. The Kupffer phase of S-CEUS is helpful for the real-time guidance during performing MWA.

5 Analysis of risk factors for and prognostic significance of microvascular invasion in hepatocellular carcinoma

XIE Weixuan , BAI Yang , FANG Zheng , ZHU Qingzhou , LUO Kunlun

2022, 31(7):890-895. DOI: 10.7659/j.issn.1005-6947.2022.07.005

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Background and Aims Hepatocellular carcinoma (HCC) is a relatively common malignant tumor in China, for which, radical resection is the primary treatment option, but the postoperative recurrence still seriously affects patients' prognosis. Among various influencing factors, microvascular invasion (MVI) is considered to be an important indicator for postoperative recurrence in HCC patients. Therefore, this study was performed to investigate the risk factors for MVI in HCC patients and the impact of MVI on prognosis of patients after radical surgery, so as to provide more complete data for clinical reference.Methods The clinicopathologic data of 150 HCC patients undergoing radical surgery at Department of Hepatobiliary Surgery, the 904th Hospital of Joint Logistic Support Force of PLA from February 2017 to February 2020 were retrospectively collected. Of the patients, 42 cases had MVI and 108 cases had no MVI as identified by pathological examination. The influencing factors for MVI were analyzed by comparison of the clinical data of the two groups of patients, and the postoperative survival status of the two groups of patients was analyzed by comparing the follow-up data.Results The results of univariate analysis showed that the maximum tumor diameter, preoperative α-fetoprotein (AFP) level, and preoperative platelet (PLT) count were significantly associated with the incidence of MVI in HCC patients (all P<0.05). The results of multivariate analysis revealed that the maximum tumor diameter (>5 cm), preoperative AFP level (≥400 μg/L), and preoperative PLT count (>200×10⁹/L) were also independent risk factors for MVI in HCC patients (all P<0.05). Follow-up was conducted in all the 150 patients for 12 to 48 months with a median time of 26 months. In patients with MVI compared with those without MVI, the 1- and 2-year overall survival rates were significantly decreased (76.19% vs. 91.67%, P<0.05, 47.20% vs.78.70%, P<0.05), and the median survival time was significantly shortened (23 months vs. 34 months, P<0.05).Conclusion The risk of MVI is increased in HCC patients with relatively large tumor size, high preoperative AFP level and high preoperative PLT count. For these patients, rigorous postoperative follow-up should be performed, so that subsequent treatment can be provided timely to improve their survival as soon as they develop signs of recurrence.

6 Predictive value of preoperative gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging for microvascular invasion in hepatocellular carcinoma

CHEN Chuang , HE Jian , FU Xu , SUN Shiquan , TANG Min , MAO Liang , JIN Yang , DING Zhilong , QIU Yudong

2022, 31(7):896-904. DOI: 10.7659/j.issn.1005-6947.2022.07.006

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Background and Aims Microvascular invasion (MVI) is an important risk factor for early postoperative recurrence of hepatocellular carcinoma (HCC). For HCC accompanied by MVI, anatomic liver resection or hepatectomy with a wide resection margin may increase the elimination rate of MVI, thereby reduce the recurrence and improve the disease-free and overall survival of patients. However, the diagnosis of MVI is based on postoperative histopathology, so accurate preoperative prediction of MVI is of great value for the development of individualized treatment plans for HCC. The greatest advantage of gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) lies in the specific imaging performance during the hepatobiliary phase. Therefore, the Gd-EOB-DTPA enhanced magnetic resonance imaging (EOB-MRI) performed in the hepatobiliary phase can clearly show the boundary of the lesion, and greatly improve the ability of the lesion display and diagnosis. This study was conducted to analyzed the preoperative EOB-MRI imaging characteristics and determine its predictive value for MVI in HCC patients.Methods The clinicopathologic and imaging data of 147 HCC patients who underwent preoperative EOB-MRI examination and radical hepatectomy from July 2014 to June 2017 in the Department of Hepatobiliary Surgery of Drum Tower Hospital of Nanjing University were reviewed. The risk factors for MVI were analyzed, and the predictive effectiveness of EOB-MRI was determined.Results Among the 147 patients, 49 cases were MVI positive and 98 cases were MVI negative. The results of univariate analysis showed that tumor size (P=0.001), non-nodular type tumor on the hepatobiliary phase (P<0.001), peritumoral enhancement in arterial phase (P=0.016), rim enhancement in arterial phase (P=0.014), mixed signal intensity of tumor on hepatobiliary phase (P=0.001) and peritumoral hypointensity on hepatobiliary phase (P<0.001) were predictors for MVI. The results of multivariate analysis showed that non-nodular type tumor on hepatobiliary phase (OR=5.075, 95% CI=1.587-16.223, P=0.006), mixed signal intensity of tumor on hepatobiliary phase (OR=2.750, 95% CI=2.679-18.977, P=0.030), peritumoral hypointensity on hepatobiliary phase (OR=7.130, 95% CI=2.679-18.977, P<0.001) were independent predictors for MVI. For predicting MVI, the sensitivity of the three EOB-MRI imaging features (the gross type of tumor, mixed signal intensity of tumor on hepatobiliary phase and peritumoral hypointensity on hepatobiliary phase) was 89.8%, 57.1% and 61.2%, and their specificity was 51.0%, 72.4% and 89.8%, respectively. The specificity reached 98.0% by simultaneous presence of the three EOB-MRI imaging features.Conclusion Non-nodular type tumor, mixed signal intensity of tumor and peritumoral hypointensity on hepatobiliary phase are independent predictors for MVI. The simultaneous presence of the three EOB-MRI imaging features has a high specificity for predicting MVI.

7 Expression of tubulin ε and δ complex 2 in hepatocellular carcinoma and its relation with prognosis of patients

XIAO Xuelian , TU Kangsheng

2022, 31(7):905-912. DOI: 10.7659/j.issn.1005-6947.2022.07.007

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Background and Aims The numbers of new cases and deaths of liver cancer (hepatocellular carcinoma accounts for 75%-85%) per year rank the fifth and second among those of all cancers diagnosed in China. The molecular mechanisms for HCC growth, metastasis, immune escape and treatment resistance are complex, which are the current research hotspots and difficult issues. Studies have demonstrated that the expression of tubulin ε and δ complex 2 (TEDC2) is up-regulated in a variety of malignant tumors and is associated with the prognosis. However, the clinical significance of TEDC2 in HCC has not yet been described. Therefore, this study was conducted to explore the expression of TEDC2 in HCC and its relation with the prognosis of patients.Methods The transcriptional profiles and clinicopathologic data of liver cancer were downloaded from TCGA and ICGC databases. The pan-cancer expression analysis of TEDC2 was performed through the GEPIA2 website. The relationship between TEDC2 expression and the prognosis of patients was analyzed by Kaplan-Meier method. The prognostic factors for patients were determined by univariate and multivariate Cox analyses. The biological functions associated with the expression of TEDC2 were analyzed by gene set enrichment analysis (GSEA).Results Pan-cancer analysis showed that TEDC2 was a risk factor for 6 different cancers that included ACC (adrenocortical carcinoma), KIRC (kidney renal clear cell carcinoma), KIRP (kidney renal papillary cell carcinoma), LAML (acute myeloid leukemia), LIHC (liver hepatocellular carcinoma), LUAD (lung adenocarcinoma). Analyses of data from both TCGA and ICGC showed that TEDC2 expression in liver cancer tissues was significantly higher than that in normal tissues (both P<0.05). The expression of TEDC2 was related to TNM stage, T stage ang histological grade (all P<0.05), and was not associated with sex and age (both P>0.05). Survival analysis found that patients with high TEDC2 expression had shorter overall survival and disease-free survival than those with low TEDC2 expression (both P<0.05). Univariate and multivariate Cox analyses identified that TNM stage, T stage and TEDC2 expression were prognostic risk factors for HCC, but only TEDC2 expression was an independent prognostic factor in both TCGA and ICGC cohorts (all P<0.05). Results of GSEA showed that pathways related to cell proliferation were enriched in the tissues with high TEDC2 expression.Conclusion The expression of TEDC2 is increased in liver cancer tissue, and is an independent prognostic factor for liver cancer. Its high expression is closely associated with the unfavorable prognosis of patients, and the mechanism may be related to the enhanced activity of cell proliferation.

8 Roles of adenosine deaminase RNA-specific adenosine deaminase 1 and Caveolin-1 in sepsis-related liver injury and the mechanism

YIN Chaoqi , TAO Ruyi , WANG Shaohua , CHEN Jia , TANG Fengjie , LIU Can , LIU Daisong , CHEN Shuyue , ZHOU Jianda , CHEN Fengyuan

2022, 31(7):913-919. DOI: 10.7659/j.issn.1005-6947.2022.07.008

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Background and Aims The pathogenesis of sepsis-related liver injury (SRLI) remains unclear, and the inflammatory damage of bacterial lipopolysaccharides (LPS) to the hepatic endothelial cells may be an important process. Previous studies have suggested that RNA-specific adenosine deaminase 1 (ADAR1) may be involved in local and systemic inflammatory responses during endothelial stress through regulating the endothelial cell function-related protein Caveolin-1 (Cav-1). Therefore, this study was conducted as a preliminary assessment to analyze the roles of ADAR1 and Cav-1 in SRLI, so as to help find a new approach for early prevention and management of SRLI.Methods Mouse sepsis models were induced in 20 ADARl knockout mice (ADAR1^ECKO) and 20 wild-type mice (ADAR1^flox/flox)by injection of LPS (20 mg/kg). Ten mice in each group were sacrificed at 6 h after LPS injection, the liver tissues were harvested for histopathological observation by HE staining and the liver sinusoidal endothelial cells (LSECs) were isolated for observation of the expressions of Cav-1 and its downstream protein VE-cadherin by cellular immunofluorescence. The remaining mice in the two groups were used for survival observation. In LSECs from normal wild-type mice after ADARl siRNA transfection, the proliferative ability was determined by endothelial tube formation assay, and the expressions of the relevant downstream proteins of Cav-1 were determined by Western blot analysis.Results The results of survival observation showed that the time of death of ADAR1^ECKO mice was earlier than that of ADAR1^flox/flox mice, and the survival rate of ADAR1^ECKO mice was lower than that of ADAR1^flox/flox mice after LPS injection (both P<0.05); the results of histopathological showed that the liver injury in ADAR1^ECKO was severe than that in ADAR1^flox/floxmice at 6 h after LPS injection; the results of cellular immunofluorescence showed that the expressions of Cav-1 and VE-cadherin in LSECs were lower from ADAR1^ECKO mice than those from ADAR1^flox/flox mice. In LSECs from normal wild-type mice after ADARl siRNA transfection, the tube formation ability was decreased, and the expression of Cav-1 downstream protein VE-cadherin was down-regulated, while the expression of β-Catenin had no obvious change.Conclusion The down-regulation or functional deficiency ADAR1 can cause the aggravation of SRLI, and the mechanism is probably associated with its regulating the activity of the Cav-1/VE-cadherin pathway. Thus, activation of the ADAR1/Cav-1/VE-cadherin pathway is potentially an effective strategy for prevention and treatment of SRLI.

9 Application of intraoperative ultrasound and contrast-enhanced intraoperative ultrasound in surgical treatment of giant hepatic malignant tumor (with video)

WANG Zicheng , DUAN Wenbin , WEI Rongguang , YANG Jianhui , DUAN Xiaohui , MAO Xianhai , LIU Changjun , GONG Weizhi

2022, 31(7):920-929. DOI: 10.7659/j.issn.1005-6947.2022.07.009

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Background and Aims Giant hepatic malignant tumor are generally poorly differentiated and often associated with vascular invasion. In recent years, the therapeutic efficacy for giant hepatic malignant tumor has been improved with the progress of both regional and comprehensive treatment. Surgical excision is one of the main treatment modalities. However, the operation is often difficult due to the intraoperative complexity such as tumor rupture, tumor thrombus spread, and omission of metastasis, which may cause the uncertainty of the treatment results. This study was performed to investigate the application and significance of intraoperative ultrasound (IOUS) and intraoperative contrast-enhanced ultrasound (CEIOUS) in the surgical treatment of giant hepatic malignant tumor, so as to help optimize the surgical procedure and obtain better oncological results.Methods The clinical data of 28 patients with giant hepatic malignant tumor undergoing surgical treatment under guidance of IOUS and CEIOUS at Hunan Provincial People's Hospital from January 2019 to August 2021 were retrospectively analyzed. All patients underwent laparotomy, and the pathological results, surgical methods, tumor size, tumor thrombus and intrahepatic metastasis, operative time, intraoperative bleeding and blood transfusion volume, postoperative hospital stay and postoperative complications were statistically analyzed.Results All patients underwent open surgery. The incisions included the inverse L-shaped incision (6 cases), fishhook-shaped incision (9 cases) and thoracicoabdominal incision (13 cases); all hepatic segments were involved in terms of the liver resection scope for the entire group, and some patients underwent combined resection of other organs; patients (11 cases) with visible vascular tumor thrombus underwent en-block resection of the primary tumor with the tumor thrombus (5 cases) or thrombectomy by venous incision (6 cases); the intrahepatic metastases (11 cases) identified by preoperative imaging examination and IOUS or CEIOUS were treated by excision or microwave ablation. The mean operation time was (365.18±110.45) min (range 190-560 min), the average blood loss was (598.21±414.43) mL (range 100-1 800 mL), 7 patients transfused with packed red cells during operation with an average infusion volume of (714.29±328.78) mL (range 400-1 300 mL), and 6 patients received fresh frozen plasma during operation with an average infusion volume of (325.00±117.26) mL (range 150-400 mL); the average number of hepatic inflow occlusion times was 4.82±2.36 (1-12 times). The postoperative pathological results showed that there were 24 cases of hepatocellular carcinoma, 2 cases of cholangiocarcinoma, 1 case of hepatocellular carcinoma with bile duct differentiation and 1 case of hepatoblastoma; the mean maximum diameter of the tumor was (13.07±3.57) cm (range 10-22 cm); there were 24 patients with microvascular tumor thrombus (including the 11 cases with visible vascular tumor thrombus). The mean hospital stay was (14.71±4.84) d (range 8-28 d). Clavien classification of surgical complications was grade I in 23 cases, grade II in 1 case and grade IIIa in 4 cases, respectively.Conclusion The application of IOUS and CEIOUS in the resection of giant hepatic malignant tumor can help optimize the surgical strategy and operation plan, identify the relationship between the tumor and blood vessels, and locate the tumor thrombus and metastatic lesions, which is of great significance to ensure the intraoperative safety, satisfactory postoperative recovery and long-term oncological outcomes.

10 Cluster analysis of research trend and hotspot in laparoscopic liver surgery based on VOSviewer

HUANG Jie , XU Dingwei , MA Jiangyun , LI Ao , LI Xincheng

2022, 31(7):930-938. DOI: 10.7659/j.issn.1005-6947.2022.07.010

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Background and Aims The feasibility and superiority of laparoscopic hepatectomy have been fully affirmed. In recent years, domestic scholars have carried out many complex laparoscopic hepatectomy, but there is still a lack of discussion on the overall research progress of laparoscopic hepatectomy. This study was conducted to analyze the publications, research hotspots and research trends in the field of laparoscopic liver surgery, and to provide reference for relevant personnel in this field to undertake the academic studies in laparoscopic liver resection.Methods The English literature on laparoscopic hepatectomy research (research article or review article), published from January 1, 1991 to December 31, 2021, was retrieved in the Web of Science database. The retrieved data were sorted by Excel software, and the basic profiles of annual number of publications, and the contributing countries/regions, journals, institutions and authors were obtained. Clustering analysis was visualized using the VOSviewer software, and then the maps of research hotspot and development trend were created.Results A total of 4 437 documents were returned after retrieval. The data showed that Japan was the leading country with the most publications (647 papers) in the field of laparoscopic hepatectomy, followed by China (617 papers) and the United States (523 papers). The top 3 productive authors of publications were Gayet Brice from the United States (70 papers), Han Ho Seong from the Republic of Korea (58 papers), and Wakabayashi Go from Japan (58 papers). The research hotspots in this field focused on the long-term efficacy of tumor patients, subsegmental resection of the liver, robotic surgery and improvement of surgical safety.Conclusion Laparoscopic hepatectomy has been widely used worldwide owing to its advantages of small trauma and rapid recovery. In the future, Chinese scholars should not only pay attentions to the research frontiers in this field, but also should actively carry out multi-center research projects.

11 Clinical analysis of retroperitoneal solitary fibrous tumor: a report of 7 cases

JING Qi , WANG Xingjie , WANG Zijun , SHI Xiaoqiang , LIAN Jie , WEI Guangbing , LI Xuqi , WANG Shufeng

2022, 31(7):939-947. DOI: 10.7659/j.issn.1005-6947.2022.07.011

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Background and Aims Solitary fibrous tumor (SFT) is a rare subtype of soft tissue sarcoma in clinical practice. Previous studies reported that SFT occurs predominantly in the pleura, but recent studies demonstrated that it can also develop in many parts of the body. Because the occurrence rate of SFT in the retroperitoneal space is low, so there is still a lack of in-depth research on the clinical diagnosis and treatment of retroperitoneal SFT at present. Therefore, this study was performed to investigate the clinical features, diagnosis and treatment as well as the prognosis of retroperitoneal SFT through reviewing the data of 7 patients with this condition, so as to help facilitate further understanding and more attention.Methods The clinical and pathological data of 7 patients diagnosed with retroperitoneal SFT by pathological and immunohistochemical analysis after surgery or puncture biopsy in the First Affiliated Hospital of Xi'an Jiaotong University from March 2014 to September 2021 were retrospectively analyzed. The diagnosis, treatment and prognosis of the patients to summarized and analyzed.Results Among the 7 patients, 4 cases were males and 3 cases were females, with an average age of (53.3±13.2) years. The clinical symptoms were not specific, one of them had no obvious symptoms, while the other 6 cases showed varying degrees of symptoms due to tumor compression of the surrounding tissues and organs. The most common symptoms were bloating and abdominal pain. CTA examination was performed in 5 patients before operation. Among them, the tumor-feeding arteries arose from the branch of the internal iliac artery in two cases, from the internal iliac artery and the lumbar artery in one case, from the distal branch of the inferior mesenteric artery in one case, and from the splenic artery in one case, respectively. Six patients underwent radical surgical resection, of whom three cases underwent preoperative embolization and three cases underwent combined organ resection. The average operative time was (372.5±91.3) min, the average blood loss was (1 200.0±1 031.5) mL, and the average length of hospital stay was (25.7±9.3) d. For patients with and without preoperative embolization, the average length of hospital stay was (10.3±4.2) d and (11.7±2.3) d, the average drainage volume on the first postoperative day was (283.3±119.3) mL and (385.0±262.5) mL, respectively. Postoperative pulmonary infection and encapsulated retroperitoneal collections occurred in one case each among the patients without embolization. Tumor size ranged from 9 cm ×7 cm×6 cm to 25 cm×20 cm×10 cm. Microscopic examination of the tumor showed that there were spindle-shaped cells of uneven distribution with varying degrees of atypia, occasional findings of thin-walled "staghorn" vasculature, and frequent presence of collagen fibers in the interstitium. The positive rates of immunohistochemical staining for CD34 and Ki-67 were 100% (7/7), CD99 and vimentin were 100% (6/6), STAT6 was 100% (5/5), and Bcl-2 was 50% (3/6), and S-100 was 14% (1/7), respectively. During the follow-up period for 2-66 months, one case was lost to follow-up and no recurrence or metastasis was found in the other cases.Conclusion Retroperitoneal SFT has no specific clinical manifestations. Imaging examinations have guiding significance for preoperative evaluation and surgical planning, and the final diagnosis depends on the results of pathological examination and immunohistochemical analysis. Radical surgical resection is the main treatment method. Preoperative embolization has positive effect on shortening the postoperative hospital stay, reducing postoperative drainage volume and the occurrence of complications. Long-term follow-up guided by risk stratification is of great importance.

12 New advances in therapeutic mechanism and relevant treatments for unresectable hepatocellular carcinoma

LIANG Xiayi , LI Lequn , WANG Xiaobo , CHEN Jie

2022, 31(7):948-957. DOI: 10.7659/j.issn.1005-6947.2022.07.012

[Abstract](799) [HTML](1170) [PDF 802.32 K](1332)

Abstract:
Hepatocellular carcinoma (HCC) is one of the common malignant tumors of the digestive system. With the development of medical level, early diagnosis and treatment of HCC has greatly reduced the underdiagnosis and mortality rate of early HCC. However, most unresectable hepatocellular carcinoma (uHCC) have no possibility for radical resection at diagnosis, which is the main reason for HCC posing a serious threat to patients' health and lives as well as for its perennially high mortality rates. With the proposal of various treatment modalities such as local therapy, drug therapy, immunotherapy and multidimensional combination therapy, the achievement of tumor downstaging in patients with uHCC has been accelerated with improved survival benefits. In order to break the current deadlock in uHCC treatment, many scholars have expanded their research based on those regarding the disease progression mechanism, treatment and relevent anti-tumor mechanisms for HCC to explore the anti-tumor mechanisms, innovative diagnostic and treatment modalities for uHCC. Therefore, the authors review the current new achievements in immune cycle, anti-tumor mechanisms and relevant treatments for uHCC.

13 Development of efficacy evaluation system for solid tumors and its application status in targeted therapy of liver cancer

LIN Kangqiang , YU Yaqun

2022, 31(7):958-965. DOI: 10.7659/j.issn.1005-6947.2022.07.013

[Abstract](772) [HTML](1373) [PDF 695.77 K](1357)

Abstract:
With the development of targeted therapy and immunotherapy, the treatment of solid tumors has entered the era of precision medicine. As a result, several new response evaluation criteria systems for solid tumors, which are based on the traditional evaluation systems in solid tumors and comply with the requirements of targeted therapy and immunotherapy, have been developed. Here, the authors systemically present the development and current status of response evaluation systems for solid tumors, emphatically from the aspect of targeted therapy of liver cancer, hoping to provide a guidance for clinical practice.

14 Research progress of biomarkers in predicting objective efficacy of anti-PD-1/PD-L1 therapy in patients with hepatocellular carcinoma

LIU Lili , ZHANG Chengren , HAO Xiangyong , TIAN Hongwei , DENG Yuan , LI Xiong , JIANG Zhiliang , GUO Tiankang

2022, 31(7):966-974. DOI: 10.7659/j.issn.1005-6947.2022.07.014

[Abstract](876) [HTML](1170) [PDF 786.52 K](1397)

Abstract:
In recent years, anti-PD-1 /PD-L1 immunotherapy has brought new hope to patients with advanced hepatocellular carcinoma (HCC). However, only about 10%-30% of the HCC patients can benefit from anti-PD-1/PD-L1 therapy as evidenced by clinical observation. Therefore, the accurate screening of patients suitable for the anti-PD-1/PD-L1 immunotherapy has become a challenge at present. The continuous accumulation of evidence-based knowledge and the rapid development of biomarkers for precision medicine provide powerful help for the precise treatment of anti-PD-1/PD-L1 for HCC patients. The discovery of biomarkers is a major breakthrough in immunotherapy, which can not only screen patients who benefit from immunotherapy, but also avoid toxic and side effects. Here, the authors mainly address the research status and future development of biomarkers associated with anti-PD-1/PD-L1 treatment in HCC patients.

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Volume 31,Issue 7,2022 Table of Contents

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