Volume 33,Issue 2,2024 Table of Contents

1 Hunan expert consensus on comprehensive diagnosis and treatment of hepatolithiasis (2024 edition)

2024, 33(2):153-167. DOI: 10.7659/j.issn.1005-6947.2024.02.001

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Hepatolithiasis is a common disease in the central and western regions of our country, especially prevalent in Hunan province. This disease poses significant challenges in diagnosis and treatment, severely impacting public health. Due to the complex and variable nature of the disease, there are numerous and diverse treatment methods, often with unsatisfactory results, leading patients into a vicious cycle of surgery, postoperative stone residue or recurrence, reoperation, stone residue or recurrence again, ultimately resulting in life-threatening complications such as biliary cirrhosis and bile duct cancer. Therefore, it is extremely necessary to standardize the diagnosis and treatment of hepatolithiasis. 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 have organized discussions among experts in hepatobiliary surgery in the province to draft the Hunan expert consensus on comprehensive diagnosis and treatment of hepatolithiasis, aiming to provide guidance and basis for the standardized diagnosis and treatment of hepatolithiasis.

2 Research hotspots, focus, and challenges of lymph node dissection in intrahepatic cholangiocarcinoma

LIU Hongzhi , ZENG Yongyi

2024, 33(2):168-175. DOI: 10.7659/j.issn.1005-6947.2024.02.002

[Abstract](225) [HTML](228) [PDF 904.01 K](1106)

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Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignant tumor, and lymph node metastasis is one of the most important adverse prognostic factors for ICC patients. Lymph node dissection has important value in lymph node staging, prognostic guidance, and adjuvant therapy for ICC. In recent years, domestic and foreign scholars have conducted in-depth research on ICC lymph node metastasis and dissection. However, there are still different understandings and recommendations regarding ICC lymph node dissection based on different research results and consensus at home and abroad. At the same time, the scope, number, and methods of lymph node dissection vary, leading to slight differences in corresponding research results. This article provides an overview of issues related to ICC lymph node dissection, including the scope, number, method, clinical value, appropriate population, and prospective clinical research based on recent research findings, aiming to clarify the research hotspots, focus, and difficulties in this field, and to help improve the comprehensive treatment level of ICC.

3 Paying attention to the research of intrahepatic cholangiocarcinoma linked to metabolic dysfunction-associated fatty liver disease

LI Zonglong , CHEN Jialu , TANG Yue , QIN Delong , TANG Zhaohui , QUAN Zhiwei

2024, 33(2):176-183. DOI: 10.7659/j.issn.1005-6947.2024.02.003

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Over the past 20 years, the global incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) has increased dramatically, affecting more than 30% of the global population. Meanwhile, over the past 40 years, the global incidence of intrahepatic cholangiocarcinoma (ICC) has also grown by 140%. In addition, previous studies have indicated that various forms of liver inflammation are closely associated with the occurrence and development of ICC. This suggests that MAFLD may play an important role in the occurrence, development, and prognosis of ICC. This article aims to summarize the current research status of MAFLD-related ICC, review the shortcomings in existing studies, and outline future research directions to provide a foundation for further exploration and in-depth study in this field.

4 Prognostic impact of tumor size on postoperative prognosis of solitary intrahepatic cholangiocarcinoma: a multicenter retrospective analysis

FAN Ruilin , LIU Hongzhi , LIN Qizhu , HUANG Tingfeng , ZHOU Weiping , CHENG Zhangjun , LOU Jianying , ZHENG Shuguo , BI Xinyu , WANG Jianming , GUO Wei , LI Fuyu , WANG Jian , ZHENG Yamin , LI Jingdong , CHENG Shi , ZENG Yongyi

2024, 33(2):184-192. DOI: 10.7659/j.issn.1005-6947.2024.02.004

[Abstract](371) [HTML](128) [PDF 848.84 K](635)

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Background and Aims Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor with poor prognosis. Surgical resection is the preferred treatment in clinical practice, but patients often experience high rates of postoperative recurrence. the incidence of ICC has been steadily increasing over the past 30 years. Tumor size, as an important prognostic factor, significantly affects the survival outcomes of patients. This study was conducted to investigate the impact of tumor size on the prognosis of patients with solitary ICC after radical resection, so as to provide more accurate prognostic assessment for clinical decision-making.Methods The clinicopathologic data of 654 patients who underwent radical resection and were pathologically diagnosed with ICC between December 2011 and December 2017 in 13 hospitals across China were retrospectively analyzed. Cox regression analysis was used to identify prognostic factors for ICC patients, Kaplan-Meier method was used to plot survival curves, and Log-rank test was used to compare overall survival (OS) differences among patients with different tumor sizes.Results A total of 307 patients were included. There were 40 cases (13.03%) with tumor size ≤3 cm, 177 cases (57.65%) with tumor size >5 cm, and 90 cases (29.32%) with tumor size >3-5 cm. Cox regression analysis revealed that margin status, pathological lymph node status, satellite nodules, and tumor size >5 cm were independent risk factors for the prognosis of solitary ICC patients (all P<0.05). The 1-, 3-, and 5-year OS rates for patients with tumors ≤3 cm were 83.3%, 73.8%, and 54.7%, for patients with tumors >3-5 cm were 81.1%, 40.7%, and 36.1%, and for patients with tumors >5 cm were 72.1%, 37.7%, and 29.0%, respectively (P=0.021). Patients with different tumor sizes were grouped and compared based on whether lymph node dissection was performed. The results showed that in ICC patients with tumor size ≤3 cm, there was no significant difference in OS rate between the two groups (P=0.780); in patients with tumor size >3-5 cm, those not undergoing lymph node dissection had significantly higher OS rate than those undergoing lymph node dissection (P=0.017); in patients with tumor size >5 cm, those who underwent lymph node dissection had significantly higher OS rate than those who did not (P=0.025).Conclusion In patients with solitary ICC, those with tumors ≤3 cm have a relatively better prognosis. For patients with solitary ICC and tumors >5 cm, lymph node dissection surgery is recommended.

5 Analysis of risk factors for perineural invasion in intrahepatic cholangiocarcinoma and the efficacy of adjuvant chemotherapy

LI Qi , CHEN Chen , LIU Hengchao , LEI Jianjun , ZHANG Dong , GENG Zhimin

2024, 33(2):193-201. DOI: 10.7659/j.issn.1005-6947.2024.02.005

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Background and Aims In recent years, the clinical value of perineural invasion for prognosis assessment and treatment decision support in patients with intrahepatic cholangiocarcinoma (ICC) has been increasingly recognized. There is growing evidence that adjuvant chemotherapy can improve the prognosis of ICC patients. However, there remains some controversy regarding whether adjuvant chemotherapy can effectively improve the overall survival (OS) of ICC patients with perineural invasion. Therefore, this study was performed to explore the risk factors for perineural invasion in ICC and analyze the efficacy of adjuvant chemotherapy for patients with concurrent perineural invasion, so as to provide support for clinical decision-making.Methods The clinicopathologic data of 259 patients who underwent curative-intent resection for ICC in the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to December 2022 were retrospectively collected. The risk factors for perineural invasion in ICC patients, factors influencing postoperative prognosis of patients, and the impact of adjuvant chemotherapy on prognosis were analyzed.Results Among the 259 patients, 17.7% (46/259) had concomitant perineural invasion. The median OS time for patients without perineural invasion was 25.0 months, with 1-, 3-, and 5-year overall survival rates of 71.3%, 38.2%, and 26.6%, respectively. For patients with perineural invasion, the median OS time was 10.0 months, with 1-, 3-, and 5-year overall survival rates of 39.1%, 21.4%, and 0.0%, respectively. The difference in survival rates between the two groups was statistically significant (χ²=8.400, P=0.004). The preoperative total bilirubin level, CEA level, CA19-9 level, viral hepatitis, intrahepatic stones, liver function Child-Pugh classification, tumor location, tumor size, vascular invasion, N stage, and TNM stage were significantly associated with perineural invasion in ICC (all P<0.05). CA19-9 level (OR=2.265, 95% CI=1.061-4.833), intrahepatic stones (OR=4.064, 95% CI=1.809-9.130), vascular invasion (OR=3.286, 95% CI=1.551-6.964), and N stage (OR=2.365, 95% CI=1.149-4.869) were independent risk factors for perineural invasion in ICC (all P<0.05). Prognostic analysis showed that CA19-9 level (HR=1.615, 95% CI=1.142-2.283), intrahepatic bile duct stones (HR=2.093, 95% CI=1.401-3.127), vascular invasion (HR=1.563, 95% CI=1.032-2.367), perineural invasion (HR=2.120, 95% CI=1.392-3.229), and N stage (HR=2.304, 95% CI=1.320-4.022) were independent risk factors for OS after curative-intent resection for ICC (all P<0.05), while adjuvant chemotherapy was an independent protective factor for overall survival after ICC surgery (HR=0.533, 95% CI=0.369-0.770, P<0.05). Further analysis showed that adjuvant chemotherapy could effectively prolong the median OS time in both the entire group of ICC patients and those with perineural invasion (both P<0.05), but its effect on prolonging median OS time in ICC patients without perineural invasion was not significant (P>0.05).Conclusion CA19-9 level, intrahepatic stones, vascular invasion, and N stage are closely related to perineural invasion in ICC. Patients with concomitant perineural invasion have poorer postoperative prognosis, but adjuvant chemotherapy can effectively improve the prognosis of such ICC patients.

6 Predictive value of the number of positive lymph nodes for the postoperative prognosis of intrahepatic cholangiocarcinoma patients undergoing radical resection

XIE Weixuan , BAI Yang , ZHU Qingzhou , LUO Kunlun

2024, 33(2):202-209. DOI: 10.7659/j.issn.1005-6947.2024.02.006

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Background and Aims The incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in recent years. This disease often presents insidiously with few obvious symptoms, leading to a low rate of early diagnosis. Radical resection remains the only potential curative treatment, but due to reasons such as widespread tumor metastasis, inadequate residual liver reserve, and poor general condition of patients, the rate of radical resection is low. Therefore, this study was performed to investigate the relationship between the number of positive lymph nodes and the postoperative prognosis of ICC patients, in order to provide references for the prognosis evaluation of ICC surgery and guidance for postoperative treatment strategies.Methods The clinical data of 150 ICC patients undergoing radical resection in the Department of Hepatobiliary Surgery, the 904th Hospital of Joint Logistic Support Force of PLA from September 2017 to September 2020 were retrospectively collected. Factors influencing postoperative survival of patients and the differences in postoperative survival among patients with different numbers of positive lymph nodes (N0: no lymph node metastasis; N1: less than 3 lymph node metastases; N2: 3 or more lymph node metastases) were analyzed.Results Univariate analysis showed that preoperative levels of CA19-9 and AFP, margin status, and the number of positive lymph nodes were significantly associated with postoperative survival of ICC patients (all P<0.05). Multivariate analysis revealed that margin status (P=0.003), preoperative CA19-9 level (P=0.008), and the number of positive lymph nodes (P<0.001) were independent risk factors affecting postoperative prognosis. The 1-, 2-, and 3-year postoperative survival rates of all 150 ICC patients were 50.67%, 24.67%, and 17.33%, respectively. The survival rates of 62 N0 patients were 79.03%, 43.55%, and 32.25% at 1, 2, and 3 years, respectively; those of 36 N1 patients were 47.22%, 27.78%, and 16.67%, respectively; and those of 52 N2 patients were 19.23%, 0, and 0, respectively. There was a statistically significant difference in overall survival among the three groups with different lymph node profiles (χ²=33.516, P<0.001), and the survival rates sequentially decreased in N0, N1, and N2 patients (all P<0.05).Conclusion The number of positive lymph nodes is an independent risk factor influencing the postoperative prognosis of ICC patients. Using 3 positive lymph nodes as a cutoff value, combined with assessment of other relevant factors, can improve the risk stratification of ICC patients in clinical practice and provide a theoretical basis for postoperative treatment strategies for ICC.

7 Efficacy and safety of combined hepatic artery resection and reconstruction in laparoscopic radical surgery for middle and lower bile duct cancers: a report of 3 cases (with video)

YANG Fengxia , HE Yonggang , ZHANG Ying , YOU Nan , TANG Yichen , LI Jing , ZHENG Lu , HUANG Xiaobing

2024, 33(2):210-218. DOI: 10.7659/j.issn.1005-6947.2024.02.007

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Background and Aims In clinical practice, lower bile duct cancers are more commonly encountered among cancers in the middle and lower segments of the bile ducts. Lower bile duct cancers are generally treated with pancreaticoduodenectomy, while middle bile duct cancers can be managed with pancreaticoduodenectomy, radical resection of bile duct cancer, and choledochojejunostomy. Bile duct cancers in the middle and lower segments are more prone to invasion of the portal vein due to their proximity, whereas invasion of the hepatic artery is relatively less common due to its adventitial sheath. However, when hepatic artery invasion occurs, it poses higher technical challenges as it often requires combined hepatic artery resection and reconstruction to achieve R₀ resection. Although hepatic artery resection and reconstruction are gradually becoming more mature in practice at present, there is a lack of experience in performing laparoscopic hepatic artery resection and reconstruction, and further accumulation is needed. Therefore, this study retrospectively analyzed the clinical data of three patients who underwent laparoscopic combined hepatic artery resection and reconstruction and evaluated the short-term results, so as to provide preliminary experience for clinical practice.Methods The clinical data of three patients undergoing radical surgery combined with laparoscopic hepatic artery resection and reconstruction for middle and lower bile duct cancers in the Department of Hepatobiliary Surgery of the Second Affiliated Hospital of the Army Medical University from November 2021 to November 2022 were retrospectively analyzed.Results Among the three patients, there was one female and two males, aged 61, 65, and 69 years, respectively. Case 1 with a middle bile duct cancer underwent combined resection and reconstruction of the right hepatic artery and portal vein, bile duct cancer resection, bilioenterostomy, hilar cholangioplasty, and lymph node dissection, due to tumor invasion of the right hepatic artery and portal vein, and negative margins at the lower end of the bile duct. Case 2 had a lower bile duct cancer with tumor invasion of the replaced right hepatic artery and portal vein, and underwent combined resection and reconstruction of the replaced hepatic artery, portal vein, and laparoscopic pancreaticoduodenectomy (LPD). Case 3 had a lower bile duct cancer with tumor invasion at the gastroduodenal artery and hepatic artery bifurcation, and underwent laparoscopic combined hepatic artery resection and reconstruction along with LPD. After operation, case 2 developed a grade B pancreatic fistula with abdominal infection, which was improved after 12 d of treatment and was discharged after tube removal. Cases 1 and 3 both recovered well without pancreatic fistula or bile leakage, and follow-up examinations showed good blood supply to the hepatic artery. None of the three cases required unplanned readmission within 30 d. During follow-up, case 2 showed tumor marker elevation and recurrence 13 months after operation, while cases 1 and 3 showed no tumor recurrence at 1 year after operation.Conclusion When middle and lower bile duct cancers are concurrently associated with invasion of the portal vein and hepatic artery, simultaneous hepatic artery/replaced right hepatic artery resection and reconstruction during portal vein resection can be performed to improve the resection rate of bile duct cancer, which is safe, feasible, and effective.

8 Construction of a nomogram predictive model for the risk of intrahepatic cholangiocarcinoma based on dyslipidemia and related factors

XU Zheng'ao , LIANG Xiao

2024, 33(2):219-226. DOI: 10.7659/j.issn.1005-6947.2024.02.008

[Abstract](207) [HTML](181) [PDF 848.57 K](711)

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Background and Aims Intrahepatic cholangiocarcinoma (ICC) is insidious in onset and progresses rapidly, often causing patients to miss the optimal surgical window when diagnosed. The mechanism underlying ICC occurrence remains unclear, potentially involving multiple factors, and dyslipidemia currently is identified as one of the risk factors. Therefore, this study was conducted to investigate the association between dyslipidemia and other risk factors with the occurrence of ICC, and to construct a nomogram prediction model, so as to facilitate early prevention for high-risk individuals for ICC and ultimately reduce the incidence rate.Methods A retrospective analysis was conducted on 5 906 liver surgery patients admitted in the Department of General Surgery of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, from January 2015 to January 2023. Among them, ICC patients and non-cancer patients were designated as the case group and control group, respectively. Basic data and biochemical indicators were collected before treatment. Lipid indexes and other risk factors were included in univariate and multivariate regression analyses to identify independent risk factors for ICC occurrence. A nomogram prediction model was constructed to assess the impact of each factor. The clinical predictive performance of the nomogram model was evaluated using receiver operating characteristic (ROC) curve, calibration curve, and decision curve.Results A total of 351 ICC patients and 2 145 non-cancer patients were included. Univariate analysis showed that the sex, age, and the proportion of diabetes, hypertension, cirrhosis, hepatitis B, history of bile duct stones, and history of schistosomiasis, as well as the serum triglycerides, serum total cholesterol, and serum high-density lipoprotein cholesterol (HDL-C) levels were significantly different between the two groups (all P<0.05). Logistic multivariate regression analysis revealed that age, hypertension, diabetes, hepatitis B, cirrhosis, and low blood HDL-C (<0.83 mmol/L) were independent risk factors for ICC occurrence, while a history of intrahepatic bile duct stones was a protective factor against ICC occurrence (all P<0.05). A nomogram prediction model for ICC occurrence constructed based on these risk factors had an area under the ROC curve of 0.771 (95% CI=0.744-0.797, P<0.001). The calibration curve showed good fit between the predicted and actual curves, and the decision curve indicated that the model had good clinical benefits and efficacy at risk thresholds of approximately 0.1-0.4, and its performance surpassed that of a single indicator.Conclusion Low blood HDL-C is closely associated with ICC occurrence. The nomogram prediction model constructed based on low blood HDL-C and other six factors can provide references for the prevention and clinical treatment of ICC.

9 Relations of timing of hepatectomy with clinical efficacy and prognosis in radical surgery for T1b/T2 stage gallbladder cancer

LIN Xuanhan , TIAN Yitong , CHEN Zhehan , ZHOU Xueyin , ZHANG Jinming , HU Jiahao , ZHOU Enjie , ZHANG Bin , SHEN Jiliang , FANG Yifeng , CAO Jiasheng , CHEN Mingyu

2024, 33(2):227-235. DOI: 10.7659/j.issn.1005-6947.2024.02.009

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Background and aims Gallbladder cancer (GBC) is the most common malignancy of the biliary system. According to the AJCC TNM staging system (8th edition), T1b/T2 stage GBC patients require radical surgery, including cholecystectomy, hepatectomy, and regional lymph node dissection. Timing options for surgery include cholecystectomy combined with hepatectomy and secondary hepatectomy based on postoperative pathological diagnosis of GBC. Currently, there is limited research on the timing of hepatectomy in radical surgery for GBC. Therefore, this study was perfromed to investigate the impact of timing selection for hepatectomy during radical surgery for GBC on perioperative variables and long-term prognosis of patients.Methods The data of 114 patients with T1b/T2 stage GBC who underwent radical surgery in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, from January 2011 to August 2018, were retrospectively collected. Among them, 82 patients underwent cholecystectomy combined with hepatectomy (one-stage group), and 32 patients underwent secondary hepatectomy after cholecystectomy (two-stage group). After balancing the baseline data of the two groups using propensity score matching (PSM), differences in overall survival (OS) and disease-free survival (DFS) were compared, factors influencing OS and DFS of patients were analyzed, and differences in operative time and length of hospital stay between the two groups were also compared. Additionally, within the two-stage group, differences in perioperative indicators and prognosis were compared between patients with different time intervals for surgery (≤20 d vs. >20 d).Results After 1:1 PSM, there were 28 cases in each group, with statistically significant difference only in the time of GBC diagnosis (P<0.05), while other baseline data were balanced and comparable (all P>0.05). Survival analysis showed no statistically significant differences in OS and DFS between the two groups (all P>0.05). The analysis of risk factors revealed that only male gender was an independent risk factor for OS (HR=2.237, 95% CI=1.119-4.473, P=0.023), while timing of surgery and other factors showed no significant relationship with OS and DFS (all P>0.05). There were no statistically significant differences in operative time and length of hospital stay between the two groups (all P>0.05). Different time intervals for secondary hepatectomy had no significant impact on perioperative variables and prognosis of patients (all P>0.05).Conclusion For T1b/T2 stage GBC patients, secondary hepatectomy has a comparable impact on efficacy and long-term prognosis compared to one-stage hepatectomy. Moreover, different time intervals for secondary hepatectomy within a 4-week window do not significantly affect prognosis.

10 Clinical application value of indocyanine green fluorescence navigation in day-surgery of laparoscopic cholecystectomy

YU Fan , JIN Liming , LIU Jie , SHANG Minjie , WANG Zhimin , WEI Fangqiang

2024, 33(2):236-243. DOI: 10.7659/j.issn.1005-6947.2024.02.010

[Abstract](190) [HTML](127) [PDF 777.05 K](619)

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Background and Aims In recent years, there has been a gradual increase in the adoption of day-surgery of laparoscopic cholecystectomy (DSLC). Given that patients usually undergo admission, surgery, and discharge within 24 h, DSLC demands higher standards of safety and efficiency. Moreover, excessive visceral fat in some overweight obese patients may affect the anatomical structure of the extrahepatic bile ducts during DSLC. Indocyanine green (ICG) fluorescence navigation may aid in identifying bile duct structures during DSLC, thus preventing bile duct injuries. Currently, there are few reports on the application of ICG fluorescence navigation in DSLC. Therefore, this study was performed to investigate the clinical application value of ICG fluorescence navigation in DSLC.Methods The clinical data of 55 patients who underwent DSLC in Zhejiang Provincial People's Hospital from July 2021 to October 2023 were retrospectively analyzed. Patients were divided into a fluorescence surgery group (22 cases) and a conventional surgery group (33 cases) based on whether ICG fluorescence navigation was used during operation. The general data, operative time, time for dissection of the Calot's triangle, estimated blood loss, and identification rate of extrahepatic bile ducts were compared between the two groups, and the impact of overweight obesity (BMI≥24 kg/m²) on the identification of extrahepatic bile ducts was also analyzed.Results There were no significant differences in general data, proportion of overweight obese patients, operative time, time for dissection of the Calot's triangle, and estimated blood loss between the fluorescence surgery group and the conventional surgery group (all P>0.05). Before dissection of the Calot's triangle, the identification rates of the cystic duct and common bile duct in the fluorescence surgery group were significantly higher than those in the conventional surgery group (59.1% vs. 21.2%, P=0.009; 50.0% vs. 18.2%, P=0.018). After dissection of the Calot's triangle, the identification rates of the common bile duct, hepatic duct, and cystic duct-common bile duct junction in the fluorescence surgery group were significantly higher than those in the conventional surgery group (100.0% vs. 69.7%, P=0.004; 100.0% vs. 33.0%, P<0.000 1; 86.4% vs. 27.3%, P<0.000 1). In the fluorescence surgery group, the identification rate of the common bile duct in overweight obese patients was significantly lower than that in non-overweight obese patients before dissection of the Calot's triangle (50.0% vs. 92.8%, P=0.039), while there was no significant difference in the identification rate of extrahepatic bile ducts between them after dissection of the Calot's triangle (P>0.05). Comparison between overweight obese patients in the fluorescence surgery group and the conventional surgery group showed that there was no significant difference in the identification rate of extrahepatic bile ducts between the two groups before dissection of the Calot's triangle (P>0.05),while the identification rates of the hepatic duct and cystic duct-common bile duct junction in the fluorescence surgery group were significantly higher than those in the conventional surgery group after dissection of the Calot's triangle (100.0% vs. 25.0%, P=0.001; 87.5% vs. 16.7%, P=0.005).Conclusion The application of ICG fluorescence navigation in DSLC is safe and feasible; it can improve the identification rate of extrahepatic bile ducts during DSLC, and even in overweight obese patients, greatly assist surgeons in clearly identifying extrahepatic bile ducts.

11 Clinical efficacy of laparoscopic versus open hepatectomy in the treatment of hepatocellular carcinoma: a real-world comparative study

LI Jun , YAO Lei , HU Fangyuan , YE Ke , XIAO Moyan , ZHANG Gewen

2024, 33(2):244-256. DOI: 10.7659/j.issn.1005-6947.2024.02.011

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Background and Aims Currently, the indications for laparoscopic hepatectomy in the treatment of hepatocellular carcinoma (HCC) have gradually converged with those for open hepatectomy, and the feasibility, safety, and effectiveness of laparoscopic hepatectomy have been progressively confirmed. However, surgeons often exhibit selection bias in choosing the surgical method. Therefore, the choice between laparoscopic and open hepatectomy also needs careful evaluation in different patient populations and medical centers. Despite this, doubts still persist among scholars regarding the oncological outcomes of laparoscopic hepatectomy. Therefore, this study was conducted to analyze and compare the clinical efficacy of laparoscopic versus open hepatectomy in the treatment of HCC.Methods The clinical data of 517 patients who underwent hepatectomy for HCC in Xiangya Hospital, Central South University, from January 1, 2016, to December 31, 2020 were retrospectively analyzed. Of the patients, 196 cases underwent laparoscopic hepatectomy (laparoscopic group), and 321 patients underwent open hepatectomy (open surgery group). The general data, perioperative conditions, and follow-up results were analyzed and compared between the two groups of patients.Results In terms of general data, there were statistically significant differences between the laparoscopic group and the open surgery group in tumor stage, tumor diameter, preoperative albumin level, and site of liver resection (all P<0.05), while the remaining differences were not statistically significant (all P>0.05). In perioperative variables, the laparoscopic group showed better outcomes than the open surgery group in terms of median intraoperative blood loss (200.00 mL vs. 300.00 mL), median length of postoperative hospital stay (6 d vs. 8 d), postoperative liver function recovery, and incidence of postoperative complications (6.63% vs. 14.02%), all of which were statistically significant (all P<0.05). Regarding follow-up results, the laparoscopic group had superior overall survival (OS) and disease-free survival (DFS) compared to the open surgery group (OS: χ²=4.478, P=0.034; DFS: χ²=8.915, P=0.003). After balancing the general data of the two groups through propensity score matching (1∶1 matching, 51 cases in each group), the laparoscopic group still showed better postoperative hospital stay (6 d vs. 9 d) and incidence of postoperative complications (3.92% vs. 19.61%) than those in the open surgery group, but there was no statistically significant difference in OS and DFS between the two groups (both P>0.05).Conclusion Laparoscopic hepatectomy for HCC is safe and effective, which can accelerate postoperative recovery and reduce postoperative hospital stay. The long-term efficacy of laparoscopic and open hepatectomy for HCC is comparable. Laparoscopy has its own indications, and after comprehensive evaluation of patients, laparoscopic surgery should be the preferred surgical approach for HCC patients.

12 Controversies and advances in surgical treatment of hilar cholangiocarcinoma

ZHANG Yu , WANG Huijun , ZHENG Weihua , YUN Cheng , GAO Hongwei , ZHANG Junjing

2024, 33(2):257-264. DOI: 10.7659/j.issn.1005-6947.2024.02.012

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Hilar cholangiocarcinoma (HCCA) mainly occurs in the common hepatic duct, left and right hepatic duct, and their confluence, accounting for approximately 50.0% to 70.0% of all cholangiocarcinoma. It is a common malignant tumor of the biliary system, with the highest incidence in Asia. Currently, surgery is the only effective treatment for HCCA. Due to the lack of early or typical symptoms, patients often present with jaundice or significant abdominal pain, and the diagnosis is usually confirmed only when the disease has progressed. Additionally, the anatomical location of HCCA is special and complex, and the tumor exhibits biological characteristics of growth along the bile ducts and infiltrative growth. Therefore, the rates of radical surgical resection and long-term survival are relatively low. Surgical treatment of HCCA has made significant progress, but it remains a challenge for surgeons. There are still many controversies in surgical treatment, with new points of contention continually emerging, such as the necessity and methods of preoperative biliary drainage, solutions for inadequate remnant liver volume, the extent of liver resection, the scope of lymph node dissection, the value of combined vascular resection and liver transplantation, and application of minimally invasive surgery. The authors discuss these controversies based on the most recent literature, aiming to promote a correct understanding of HCCA, standardize its treatment, and improve patient prognosis.

13 Progress in targeted therapy against vascular endothelial growth factors and their receptors for biliary tract cancers

YANG Yang , WANG Wanxiang

2024, 33(2):265-272. DOI: 10.7659/j.issn.1005-6947.2024.02.013

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Biliary tract cancers (BTC) are classified according to anatomical sites into gallbladder cancer, intrahepatic bile duct cancer, and extrahepatic bile duct cancer. Their onset is insidious, early diagnosis is difficult, and the prognosis for patients is poor. Surgical treatment, as the only curative treatment method, is not ideal in its effectiveness. Chemotherapy is less effective and its safety is difficult to guarantee for such patients. Targeted therapy has emerged in recent years as a novel treatment modality, targeting specific sites in tumor cells of patients, with significant improvements in both efficacy and safety compared to traditional treatment methods. Vascular endothelial growth factors and their receptors are among the targeted anti-tumor sites expressed in various solid tumors, including BTC, at relatively high levels. When combined, they transmit biological signals into cells through multiple signaling pathways, thereby regulating tumor angiogenesis and hematogenous metastasis. Targeted therapy against vascular endothelial growth factors and their receptors has achieved certain success in BTC. Bevacizumab is the first vascular endothelial growth factor inhibitor used in clinical practice, and its combination with gemcitabine-based systemic chemotherapy, immune checkpoint inhibitors, or tyrosine kinase inhibitors has shown promising results in BTC, although some outcomes have not met expectations, necessitating further clinical trials. Ramucirumab, a vascular endothelial growth factor receptor inhibitor, has been less studied in BTC and is currently only applied in combination with systemic chemotherapy and immune checkpoint inhibitors. Currently, there are various types of tyrosine kinase inhibitors targeting vascular endothelial growth factor and its receptor, such as lenvatinib, sorafenib, apatinib, and anlotinib. Lenvatinib is undoubtedly a focus of research in malignant tumors of the hepatobiliary system. As a multi-target tyrosine kinase inhibitor, lenvatinib combined with immune checkpoint inhibitors and systemic chemotherapy has achieved encouraging efficacy in BTC patients, while ensuring safety to a significant extent. This indicates the direction for future comprehensive treatment methods. Other tyrosine kinase inhibitors such as anlotinib and apatinib also have widely used in BTC. Various targeted drugs have been extensively studied in BTC, and some of them are single-target inhibitors. This suggests to clinical practitioners the importance of fully considering the expression of target sites in patients before administering targeted drugs, in order to achieve precise and maximum therapeutic effects. Future research should focus on both precision treatment and systemic therapy, with the sole goal of improving patient survival and enhancing their quality of life.

14 Research progress of circular RNAs and N6-methyladenosine modifications in the regulation of malignant tumors

WANG Yin'ge , LI Danxiu , ZHANG Wenyao , YANG Tao , JIN Haifeng

2024, 33(2):273-283. DOI: 10.7659/j.issn.1005-6947.2024.02.014

[Abstract](410) [HTML](288) [PDF 974.41 K](776)

Abstract:
N6-methyladenosine (m6A) is the most common epigenetic modification in eukaryotic RNAs, which is dynamically balanced and reversibly changed in organisms through the coordinated regulation of methyltransferases, demethylases, and reader proteins. It affects the splicing, processing, localization, transportation, translation, and degradation of RNAs, thereby regulating the progression of tumors. Circular RNAs (circRNAs), as the novel multifunctional non-coding RNAs, possess characteristics like structural stability, evolutionary conservation, high abundance, and tissue specificity. Additionally, they participate in regulating various physiological and pathological activities by serving as a sponge of microRNAs (miRNAs), binding proteins, translating proteins, and modulating gene transcription and splicing, and are expected to provide new molecular markers and potential drug targets for the early diagnosis and treatment of tumors. Numerous studies have indicated that m6A and circRNAs can independently regulate oncogene expressions, and there is mutual regulatory interaction between them. M6A modification can regulate circRNA biogenesis, nuclear export, degradation, translation, and innate immunity. Similarly, circRNAs can regulate m6A modification through mechanisms such as acting as a miRNA sponge or binding m6A modification enzymes. Both participate in processes such as proliferation, migration, invasion, stemness, drug resistance, and the immune microenvironment of tumor cells, which will help discover more regulatory mechanisms and therapeutic targets for tumor research. However, given the complexity of m6A modification and circRNA biology, many aspects of research still need to be clarified. For example, m6A detection technology is not yet accurate, the database of m6A-modified circRNAs is still lacking, and efficient production methods and delivery system optimization for circRNAs are still in the early stages of development. Therefore, further in-depth research is needed on the interaction network between m6A modification and circRNAs. This article reviews the characteristics, formation mechanisms, and biological functions of circRNAs, along with an in-depth discussion on the basic concepts and current research status of m6A methylation modification, and also summarizes and analyzes the interaction between m6A modification and circRNAs and their impact on the occurrence and development of malignant tumors, as well as discusses their clinical application value and prospects, aiming to offer new perspectives for early tumor diagnosis, precision treatment, prognosis assessment, and drug development.

15 China Journal of General Surgery, 2024, 33(2):284-288.

刘霁锋，陈旭，张庆凯，张桂信，李世华，李爽，尚东

2024, 33(2):284-288. DOI: 10.7659/j.issn.1005-6947.2024.02.015

[Abstract](200) [HTML](235) [PDF 922.04 K](654)

Abstract:
背景与目的 Crigler-Najjar综合征（CNS）Ⅱ型是一种由UGT1A1酶活性降低引起的极为罕见的常染色体隐性遗传病，表现为非结合型高胆红素血症。CNS Ⅱ型患者罹患胆囊结石的风险增加，但国内尚未有CNS Ⅱ型合并急性胆囊炎患者行手术治疗的相关报道，且高胆红素血症对胆囊手术治疗的影响尚不清楚。本文通过回顾1例CNS Ⅱ型合并胆囊结石胆囊炎患者的诊治情况，并结合文献复习，对该病的特点、诊疗经过进行分析、总结，以期对临床工作提供经验和借鉴。方法回顾性分析了大连医科大学附属第一医院普通外科诊治的1例CNS Ⅱ型合并急性胆囊炎患者临床资料，并复习相关文献。。结果患者为55岁男性，因“急性结石性胆囊炎，非结合性高胆红素血症”于当地医院行经皮经肝胆囊穿刺引流术（PTGD）。为求进一步手术治疗于我院就诊，通过多学科讨论分析患者临床表现、影像学特征、实验室检查结果等方面资料，认为可行手术，遂行腹腔镜下胆囊切除术（LC）。结合术后病理和基因检测结果确诊CNS Ⅱ型合并急性胆囊炎。结论 CNS Ⅱ型是一种极为罕见的遗传病，临床诊断较为困难。对于黄疸的患者在排除胆道梗阻等情况后，要警惕先天性黄疸的可能。PTGD和LC对CNS Ⅱ型患者胆红素水平影响较小，对于有手术指征的CNS Ⅱ型合并急性胆囊炎患者应尽早进行手术，以免重症感染导致胆红素水平进一步升高。

16 China Journal of General Surgery, 2024, 33(2):289-294.

卢永帆，卢铁成，魏杰，潘浩宇，尹亚刚，王定新

2024, 33(2):289-294. DOI: 10.7659/j.issn.1005-6947.2024.02.016

[Abstract](274) [HTML](243) [PDF 1.40 M](645)

Abstract:
背景与目的 副神经节瘤（PGL）是一种源自神经嵴外胚层的神经内分泌肿瘤，胆道系统是肾上腺外PGL的罕见部位。目前关于原发性胆囊副神经节瘤（PGP）的研究较少，多为个案报道，其临床表现和影像学特征不典型，致使术前诊断困难，易被漏诊或误诊。笔者通过回顾1例PGP患者的诊治经过，并结合国内外相关文献报道，总结该病的临床特点、诊断和治疗方法，以期提高临床工作者对罕见部位PGL的认识。方法回顾性分析收治的1例PGP患者的临床资料，结合国内外相关文献，探讨该病的临床特点、诊断和治疗方法。结果患者为35岁女性，因上腹部疼痛5 d入院，腹部彩超提示胆囊内有一大小约2.6 cm×2.0 cm异常强回声，呈乳头状，基底较宽，无蒂，后方无声影，改变体位不移动，考虑腺瘤。腹部CT平扫显示胆囊底部等密度软组织肿块影，增强CT显示胆囊底部类圆形、边界清楚的软组织肿块，未侵及浆膜层，动脉期明显强化，三期强化程度等同于血管强化，考虑胆囊占位性病变，性质待排。于全麻下行腹腔镜下胆囊切除，术中快速冷冻切片考虑神经内分泌肿瘤，术后病理提示为PGP。定期随访1年，未见肿瘤复发和转移，目前继续随访中。结论 PGP是一种具有潜在复发和转移特性的良性肿瘤，该病罕见且缺乏典型的临床表现及影像学特征，术前易误诊。虽然腹部增强CT显示早期显著和持续增强的病变对诊断有一定帮助，但缺乏特异性，最终确诊需依靠病理和免疫组化。手术切除是治疗该疾病的首选方法，对局限于胆囊腔内、未侵及浆膜层及周围其他脏器组织的PGL，仅行胆囊切除即可获得较满意的效果，术后应定期随访观察。

17 China Journal of General Surgery, 2024, 33(2):295-298.

李钊，冯伟，修珊珊，惠国华，梁雅静，王新伟

2024, 33(2):295-298. DOI: 10.7659/j.issn.1005-6947.2024.02.017

[Abstract](324) [HTML](229) [PDF 859.71 K](871)

Abstract:
背景与目的 石灰质胆汁是指胆囊内胆汁呈现白色或灰色石灰样糊状或固体状，亦称钙乳胆汁，其成分主要包含碳酸钙盐或草酸钙盐，临床上少有这种胆汁表现。由石灰质胆汁导致的胆囊炎及胆管炎，可统称为石灰质胆汁综合征（LBS），该类患者多数并无特异性临床表现。术前影像学诊断较为困难，多数在术后剖开胆囊后确诊，目前国内少有相关病例报道。本文报告1例LBS患者的诊治经过，并结合相关文献报道，对本病特点，形成机制等进行分析、总结，以期对临床工作提供经验和借鉴。方法回顾性分析山东省日照市中医医院2023年4月收治的1例LBS患者临床资料，结合国内外文献对该病的临床特点、影像学诊断及形成机制进行分析总结。结果患者为56岁女性，因上腹痛1个月入院。腹部CT见胆囊腔内及胆囊管内多发高密度影，胆囊壁局部增厚，胆总管直径正常，肝内外胆管无扩张。临床诊断胆囊结石伴胆囊炎，常规术前准备后行腹腔镜下胆囊切除术，术毕剖开胆囊见囊腔内充满白色糊状物质，并于胆囊颈部及胆囊管处见白色结石。术后病理学诊断：慢性胆囊炎伴腺肌瘤样增生。结论 LBS是一种罕见的临床疾病，术前主要依靠腹部X线平片或CT扫描协助诊断，病因尚不明确，其形成机制有多种可能，一般在术后确诊，预后良好。

18 China Journal of General Surgery, 2024, 33(2):299-304.

陈海敏，赵家锋，王贵福，叶俊杰，吴青松

2024, 33(2):299-304. DOI: 10.7659/j.issn.1005-6947.2024.02.018

[Abstract](205) [HTML](190) [PDF 1.07 M](780)

Abstract:
背景与目的 肝脓肿是临床上常见的疾病，而异物性肝脓肿较为罕见，尤其是经口摄入的牙签所引起的肝脓肿更是罕见。笔者回顾性分析1例误吞牙签继发肝脓肿患者的诊治经过，结合国内外文献对本疾病特点进行复习，以期为临床工作、生活习惯提供经验与教训。方法回顾性分析1例误吞牙签导致肝脓肿患者的临床资料，并复习相关文献。结果患者为31岁女性，因发热伴腹泻入院。入院后腹部CT检查考虑肝脓肿，其内存在异物可能。此患者先行B超引导下经皮肝脓肿穿刺引流术，3 d后复查肝脏超声，异物性特征物体仍然存在。遂行腹腔镜探查，术中在腹腔镜超声引导下切开病变肝脏区域、取出牙签。术中观察到十二指肠与右肝脏面存在粘连，分离粘连后未见瘘管、穿孔，考虑异物经消化道穿孔后该穿孔处自愈，术中未行消化道修补。术后痊愈出院。结论消化道吞入牙签所致异物性肝脓肿极为罕见，病程发展较长，早期发现较为困难。在其诊断中，病史及影像学检查是关键，手术是其较为彻底的治疗方式，具体手术方式应根据术前、术中情况进行选择。对于病程较长的患者，异物经消化道完全进入肝脏后，存在消化道穿孔处自愈概率。

19 China Journal of General Surgery, 2024, 33(2):305-310.

倪雅惠，秦东媛，王琳

2024, 33(2):305-310. DOI: 10.7659/j.issn.1005-6947.2024.02.019

[Abstract](223) [HTML](231) [PDF 705.23 K](847)

Abstract:
背景与目的 既往研究表明，肝硬化患者血清总胆汁酸（TBA）、高尔基体蛋白73（GP73）及糖类抗原19-9（CA19-9）的水平均有升高，但其血清水平与肝硬化严重程度之间的相关性，及三个指标彼此之间的关系尚未见文献报道。因此，本研究就此方面进行探讨，以期对临床上肝硬化患者的病情判断及预后评估提供新的思路。方法回顾性收集2021年1月—2022年12月在山西白求恩医院完成治疗和随访的80例肝硬化患者资料，根据肝功能Child-Pugh分级标准，其中A级20例、B级30例、C级30例；选择同期健康体检者80例为对照组。比较肝硬化组与对照组血清TBA、GP73、CA19-9及肝功能指标的差异，以及不同肝功能Child-Pugh分级肝硬化患者治疗前后以上指标的变化，并分析三个指标之间的相关性及其各自与肝硬化严重程度之间的相关性。结果肝硬化患者血清TBA、GP73及CA19-9水平及其他常规肝生化指标均高于对照组（均P<0.05）；在肝硬化患者中，三项指标水平均随着肝功能Child-Pugh分级的递增而升高（均P<0.05），且与其他常规肝生化指标相比，升高幅度更明显；肝硬化患者治疗后血清TBA、GP73、CA19-9水平均较治疗前明显降低（均P<0.05），但肝功能Child-Pugh分级无明显变化。肝硬化组患者血清TBA、GP73、CA19-9之间两两呈正相关，且与肝功能Child-Pugh分级也均呈正相关（均P<0.05）。结论肝硬化患者血清TBA、GP73、CA19-9水平升高，且升高程度与肝功能损害程度及治疗效果密切相关。因此，它们有望用于指导临床上肝硬化患者临床诊疗和预后评估。

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Volume 33,Issue 2,2024 Table of Contents

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