Volume 32,Issue 8,2023 Table of Contents

1 A brief discussion on the challenges of immunotherapy in biliary malignant tumors: treatment resistance and hyperprogression

YU Xiaopeng , CHEN Jialu , TANG Yue , QIN Delong , TANG Zhaohui , QUAN Zhiwei

2023, 32(8):1129-1135. DOI: 10.7659/j.issn.1005-6947.2023.08.001

[Abstract](614) [HTML](500) [PDF 753.46 K](1097)

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Immunotherapy provides a new treatment option for biliary tract cancers (BTC), especially for patients with advanced stages. Durvalumab, with its acceptable drug toxicity and significant improvement in prognosis, has emerged as a first-line treatment for advanced BTC. However, it should not be overlooked that while immunotherapy benefits BTC patients, it also faces two challenges: treatment resistance and hyperprogression. Both of these challenges have a relatively high incidence, impacting the efficacy of immunotherapy and potentially accelerating tumor progression. Here, the authors outline the immune-related biological processes involved by delving into the mechanisms underlying these two challenges to lay a foundation for developing regimens to tackle immunotherapy resistance and hyperprogression, to enhance the efficacy of immune therapy for BTC and refine the comprehensive strategy for surgical treatment of biliary tract conditions.

2 Interpretation of the updates in 2023 EASL-ILCA Clinical Practice Guidelines on the management of intrahepatic cholangiocarcinoma

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

2023, 32(8):1136-1145. DOI: 10.7659/j.issn.1005-6947.2023.08.002

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In 2023, the European Association for the Study of the Liver (EASL) and the International Liver Cancer Association (ILCA) released the latest version of the "Clinical Practice Guidelines on the Management of Intrahepatic Cholangiocarcinoma" (referred to as "new version guidelines"). In comparison to the previous version of guidelines developed by EASL-ILCA in 2014 (referred to as "old version guidelines"), the new version guidelines adopt a new question-oriented article structure, accurately focusing on crucial clinical questions that urgently need to be answered in the field of intrahepatic cholangiocarcinoma (iCCA), especially those that are not covered by the old version guidelines or need to be updated based on recent scientific progress. In response to these questions, the new version guidelines proposed corresponding recommendations, providing substantial updates to clinical guidance for iCCA in respect of classification, risk factors, diagnosis, staging, and treatment. The purpose of this article is to provide a detailed interpretation of the key updates in the EASL-ILCA new version guidelines, and also to compare and discuss the relevant content of existing iCCA guidelines worldwide. Hopefully, it can continuously promote our in-depth understanding in the clinical practice of iCCA diagnosis and treatment.

3 Analysis of the efficacy of hepatectomy combined with vascular resection and reconstruction in treatment of intrahepatic cholangiocarcinoma with vascular invasion: a multi-center retrospective analysis

YU Xiaopeng , CHEN Jialu , TANG Yue , CHEN Chen , QIU Yinghe , WU Hong , SONG Tianqiang , HE Yu , MAO Xianhai , ZHAI Wenlong , CHENG Zhangjun , LIANG Xiao , LI Jingdong , SUN Chuandong , MA Kai , GENG Zhimin , TANG Zhaohui , QUAN Zhiwei

2023, 32(8):1146-1155. DOI: 10.7659/j.issn.1005-6947.2023.08.003

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Background and Aims In the past, the invasion of major vessels (such as the portal vein and inferior vena cava) was considered a contraindication for radical resection of intrahepatic cholangiocarcinoma (ICC). With advancements in surgical techniques, the safety of liver resection combined with vascular resection and reconstruction is gradually being recognized, but its efficacy remains inconclusive. Therefore, this study was conducted to investigate the safety and efficacy of liver resection with vascular resection and reconstruction for ICC patients with vascular invasion and the value of postoperative adjuvant therapy using multi-center data from domestic institutions.Methods The clinicopathologic data of 1 040 ICC patients who underwent radical resection between January 2010 and June 2021 in 12 grade A tertiary hospitals in China were retrospectively collected. This cohort included 872 patients without vascular invasion and 168 patients with vascular invasion (among whom 35 underwent combined vascular resection and reconstruction, and 133 underwent conventional radical ICC resection without vascular resection). Overall survival (OS) was analyzed for the entire cohort and patient subgroups. The impact of vascular resection and reconstruction on major clinical variables and OS of patients with vascular invasion and the influence of postoperative adjuvant therapy on OS were analyzed.Results The median OS for the entire cohort was 18 (9.4-30.6) months. The median OS for patients without vascular invasion was 18.51 (10-32) months, while for patients with vascular invasion, the median OS was 16.3 (9.4-28) months for those without vascular resection and 10 (5.5-21.6) months for those with vascular resection and reconstruction. Survival analysis indicated that patients with vascular invasion had lower OS than those without vascular invasion, regardless of whether vascular resection was performed (all P<0.05). Vascular resection and reconstruction did not significantly improve OS for patients with vascular invasion (P=0.662). After 1∶1 propensity score matching, the median OS for patients with vascular invasion remained lower than those without vascular invasion, but the differences were not statistically significant (non-vascular invasion vs. vascular resection: 26 months vs. 21.8 months, P=0.087; non-vascular invasion vs. non-vascular resection: 27 months vs. 16 months, P=0.068), and vascular resection and reconstruction did not significantly improve OS (P=0.293). Among patients with vascular invasion, vascular reconstruction led to longer operative time and length of postoperative hospitalization than those without vascular resection (all P<0.05). In contrast, other clinical variables, such as postoperative complications, showed no significant differences (all P>0.05). Subgroup analysis of patients with similar types of vascular invasion indicated that vascular resection and reconstruction did not improve OS for patients with different kinds of vascular invasion (all P>0.05). Regardless of whether vascular resection and reconstruction were performed, postoperative adjuvant therapy positively impacted OS, but the differences were not statistically significant (both P>0.05).Conclusion Vascular invasion is a prognostic risk factor for ICC patients, and vascular resection plus reconstruction does not significantly improve patients' prognosis, possibly leading to longer operative time and length of postoperative hospitalization. Postoperative adjuvant therapy for ICC patients with vascular invasion may help improve prognosis.

4 Combined preoperative serological and imaging examinations in predicting survival benefits of patients after radical resection of intrahepatic cholangiocarcinoma

CHEN Jialu , YU Xiaopeng , TANG Yue , CHEN Chen , QIU Yinghe , WU Hong , SONG Tianqiang , HE Yu , MAO Xianhai , ZHAI Wenlong , CHENG Zhangjun , LI Jingdong , LIANG Xiao , SUN Chuandong , MA Kai , LIN Ruixin , TANG Di , GENG Zhimin , TANG Zhaohui , QUAN Zhiwei

2023, 32(8):1156-1166. DOI: 10.7659/j.issn.1005-6947.2023.08.004

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Background and Aims Intrahepatic cholangiocarcinoma (ICC) is characterized by its insidious onset and high invasiveness, often resulting in patients losing the optimal timing for surgery upon diagnosis, leading to poor 5-year survival rates following surgery. Early prediction of survival benefits from radical resection is crucial. This study was performed to predict survival benefits in ICC patients undergoing radical resection based on preoperative imaging and serum markers to provide guidance and references for clinical decisions regarding the suitability of radical resection.Methods The imaging and serological data of 821 ICC patients who underwent radical resection in 13 tertiary-grade A-class hospitals in China from January 2010 to December 2021 were retrospectively collected. Imaging data included the presence of liver mass, intrahepatic bile duct dilation, portal vein invasion, lymph node invasion, ascites, and stones. Serum markers had hemoglobin, white blood cell count, lymphocyte count, neutrophil count, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA125, alanine aminotransferase (ALT), total bilirubin (TBIL), albumin (ALB), and prothrombin time (PT). Target variables were selected through univariate and multivariate Cox regression analysis, and using these variables, a CoxPH model was constructed, and a nomogram was also visualized. Survival curves were plotted using Kaplan-Meier analysis to validate the relationship between the scores and patient outcomes. The model's predictive performance was assessed through receiver operating characteristics (ROC) and calibration curves.Results The independent prognostic factors were imaging indicators of ascites, intrahepatic bile duct dilation, lymph node invasion, and serum markers with CEA >5 μg/L, CA19-9 >37 U/mL, and CA125 >40 U/mL (all P<0.05). The CoxPH model built using the 6 variables demonstrated that patients in the high-risk group identified by the model had significantly lower 1-, 3-, and 5-year survival rates compared to the low-risk group (all P<0.05). The model exhibited good discrimination and effectiveness through the constructed nomogram. ROC curves showed that the area under the curve (AUC) for the model's predictions at 1, 3, and 5 years were 0.711, 0.721, and 0.782, respectively, surpassing the predictive efficacy of individual markers.Conclusion The prognostic model composed of preoperative CA125, ascites, intrahepatic bile duct dilation, lymph node invasion, CEA, and CA19-9 effectively stratifies patients into high- and low-risk groups and provides accurate individualized predictions of survival benefits following radical resection in ICC patients. This model offers guidance for clinical decisions regarding the suitability of radical resection.

5 Efficacy and safety of extended hepatectomy versus limited hepatectomy for type Ⅲ and Ⅳ hilar cholangiocarcinoma: a Meta-analysis

CHEN Wen , LIN Xiaodan , LIN Binsheng , HUANG Xiaojing

2023, 32(8):1167-1176. DOI: 10.7659/j.issn.1005-6947.2023.08.005

[Abstract](589) [HTML](583) [PDF 1.02 M](937)

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Background and aims Hilar cholangiocarcinoma (HC) is the most common form of extrahepatic cholangiocarcinoma in clinical practice. It is highly malignant and associated with a poor prognosis. Radical resection remains the most effective approach for achieving long-term survival in HC patients. Type Ⅲ and Ⅳ (Bismuth-Corlette classification) HC lesions are complex, with serious surgical difficulty and risk. Surgery by limited hepatectomy carries relatively low risk but may result in a higher rate of positive margins, which may affect prognosis. Conversely, extended hepatectomy may improve radical rates and survival and increase surgical risks. There is yet to be a consensus on the appropriate scope of hepatectomy for type Ⅲ and Ⅳ HC. This study evaluated the efficacy and safety of extended hepatectomy and limited hepatectomy for type Ⅲ and Ⅳ HC by a Meta-analysis to provide evidence-based guidance for clinical decision-making.Methods The clinical control studies comparing extended hepatectomy and limited hepatectomy for type Ⅲ and Ⅳ HC were collected by searching several domestic and foreign literature databases, with a time restriction from inception to November 30, 2022. Two researchers independently screened the literature and extracted data according to inclusion and exclusion criteria, and Meta-analysis was performed using RevMan 5.2 software.Results A total of 11 articles involving 844 patients with type Ⅲ or Ⅳ HC were included in the study, with 423 patients in the extended hepatectomy group and 421 patients in the limited hepatectomy group. The Meta-analysis results showed that compared to the limited hepatectomy group, the extended hepatectomy group had significantly higher radical rates (OR=4.44, 95% CI=2.65-7.45, P<0.000 01) and better clinical prognosis (HR=0.53, 95% CI=0.41-0.68, P<0.000 01). The extended hepatectomy group had a higher incidence of postoperative liver dysfunction (OR=3.00, 95% CI=1.07-8.40, P=0.04), but there were no statistically significant differences in postoperative mortality rate (OR=1.12, 95% CI=0.25-4.99, P=0.88), and incidence rates of overall complications (OR=1.44, 95% CI=0.95-2.18, P=0.09) and other individual complications (bile leakage: OR=1.44, 95% CI=0.68-3.04, P=0.34; abdominal bleeding: OR=0.77, 95% CI=0.29-2.05, P=0.60; abdominal infection: OR=1.36, 95% CI=0.50-3.71, P=0.55). Additionally, the extended hepatectomy group had significantly increased intraoperative blood loss, operative time, and hospitalization duration compared to the limited hepatectomy group (MD=153.48, 95% CI=32.63-274.33, P=0.01; MD=78.19, 95% CI=54.56-101.82, P<0.000 01; MD=2.55, 95% CI=1.61-3.50, P<0.000 01).Conclusion Extended hepatectomy can improve the radical resection rate and significantly enhance the prognosis for stage Ⅲ and Ⅳ HC. Moreover, it does not increase postoperative mortality or overall complication rates. However, an elevated risk of postoperative liver failure is associated with extended hepatectomy. Given the limitations of this study, further prospective randomized controlled trials are still needed to provide additional verification.

6 Analysis of risk factors for early recurrence of incidental gallbladder cancer after second surgery and the efficacy of adjuvant chemotherapy

LI Qi , LIU Hengchao , LI Mengke , GAO Qi , CHEN Chen , ZHANG Dong , GENG Zhimin

2023, 32(8):1177-1186. DOI: 10.7659/j.issn.1005-6947.2023.08.006

[Abstract](622) [HTML](522) [PDF 895.91 K](925)

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Background and Aims Early postoperative recurrence is a significant risk factor for poor prognosis of gallbladder cancer, and growing evidence suggests that adjuvant chemotherapy can improve the outcomes of patients. However, there have been no reports on early postoperative recurrence after the second surgery and the impact of adjuvant chemotherapy on patients with incidental gallbladder cancer (IGBC). Therefore, this study explored the risk factors for early postoperative recurrence after the second surgery in IGBC patients and analyzed the efficacy of adjuvant chemotherapy in early and non-early recurrence patients to provide clinical decision support.Methods The clinicopathologic data of 170 patients who underwent curative-intent resection for IGBC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2021 were retrospectively collected. The factors influencing early postoperative recurrence (defined as recurrence within 12 months after the second radical surgery), as well as recurrence-free survival (RFS) and overall survival (OS) after surgery of patients, were analyzed.Results Among the 170 patients who underwent curative-intent resection for IGBC, 73 (42.94%) experienced recurrence during the follow-up period, with 41 (24.12%) experiencing early postoperative recurrence. The median OS in patients with early postoperative recurrence was significantly shorter than those without early recurrence (χ²=192.910, P<0.001). The degree of pathological differentiation (OR=20.758, 95% CI=5.557-80.239), CA19-9 level (OR=7.920, 95% CI=1.557-39.771), and residual lesions (OR=8.050, 95% CI=3.06-21.160) were independent risk factors for early postoperative recurrence of IGBC (all P<0.05). The degree of pathological differentiation (HR=6.160, 95% CI=2.877-13.193), CA19-9 level (HR=2.538, 95% CI=1.297-4.965), surgical resection scope (HR=2.111, 95% CI=1.154-3.860), and residual lesions (HR=2.571, 95% CI=1.547-4.273) were independent risk factors for RFS in IGBC patients after surgery (all P<0.05). The degree of pathological differentiation (HR=3.225, 95% CI=1.461-7.121), early recurrence (HR=29.558, 95% CI=14.250-61.311), and residual lesions (HR=2.416, 95% CI=1.361-4.287) were independent risk factors for OS in IGBC patients after surgery (all P<0.05). Adjuvant chemotherapy was an independent protective factor for OS (HR=0.260, 95% CI=0.123-0.551, P<0.05). Stratified analysis based on residual lesions and early recurrence showed that adjuvant chemotherapy prolonged RFS and OS in patients with residual lesions and extended OS in early recurrence patients (all P<0.05).Conclusion Residual lesions are independent risk factors for early postoperative recurrence and prognosis in IGBC patients after the second surgery. Adjuvant chemotherapy after surgery can effectively improve the prognosis of patients with residual lesions and early recurrence.

7 Construction and validation of the prognosis model for gallbladder squamous cell carcinoma

HUANG Kun , HUANG Zhenghong , ZHAO Pan , ZHAO Pingwu , HE Yunsheng , BAI Dou

2023, 32(8):1187-1198. DOI: 10.7659/j.issn.1005-6947.2023.08.007

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Background and Aims Gallbladder squamous cell carcinoma (GSCC) is a rare histopathological subtype of gallbladder cancer, accounting for 1% to 4% of cases. This tumor type is associated with poor prognosis. Currently, the literature on GSCC mainly consists of case reports and small-sample case series. Due to the lack of large-sample high-quality clinical research evidence, there are no established treatment guidelines, consensus, or personalized prognostic assessment tools for GSCC. Therefore, this study aimed to construct prognostic nomograms for GSCC patients using large-scale real-world data from the SEER database to provide precise and individualized prognosis assessment for GSCC patients, offering valuable references for clinical decision-making.Methods Clinical data of GSCC patients pathologically diagnosed between 2000 and 2019 were extracted from the SEER database. The data were randomly divided into training and validation sets in a 7∶3 ratio. In the training set, a multivariate Cox proportional hazards model and LASSO regression were used to identify independent prognostic factors for the survival of GSCC patients. These factors constructed nomogram models to predict tumor-specific survival (CSS) and overall survival (OS) at 3 and 6 months for GSCC patients. Subsequently, the models were internally and externally validated in training and validation sets using the concordance index (C-index), ROC, and calibration curves to assess their accuracy and predictive capacity.Results A total of 257 patients were included in this study, 179 in the training and 78 in the validation set. The median follow-up times were 3 (1-7) months in the training set and 4 (2-8) months in the validation set. Baseline characteristics were comparable between the two groups. The multivariate Cox proportional hazards model analysis revealed that age, SEER stage, surgery, and chemotherapy were independent factors for OS and CSS in GSCC patients (all P<0.05). LASSO regression analysis indicated that age, SEER stage, radiotherapy, surgery, and chemotherapy were associated with OS; age, SEER stage, surgery, and chemotherapy were correlated with CSS in GSCC patients. Nomograms for predicting OS and CSS at 3 and 6 months were developed based on these independent prognostic factors. Validation results demonstrated C-index values of 0.739 (95% CI=0.700-0.780) and 0.729 (95% CI=0.660-0.800) for OS in the training and validation sets, respectively; C-index values of 0.750 (95% CI=0.710-0.790) and 0.741 (95% CI=0.670-0.810) for CSS in the same sets. ROC curve analysis indicated AUC values >0.8 in both training and validation sets. Calibration curve analysis showed good agreement between predicted and actual OS and CSS at 3 and 6 months for GSCC patients. Both were closely situated near the ideal 45° reference line, demonstrating high consistency.Conclusion Age, SEER stage, surgery, radiotherapy, and chemotherapy are independent prognostic factors for GSCC patients. The constructed nomogram prediction models exhibit favorable predictive value and facilitate personalized treatment selection for GSCC patients in the clinical setting.

8 Analysis of influencing factors for acute biliary pancreatitis in patients with cholecystolithiasis and construction of nomogram prediction model

LU Yingchao , HUANG Jinshan , XU Hongxing , SHEN Danfeng

2023, 32(8):1199-1207. DOI: 10.7659/j.issn.1005-6947.2023.08.008

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Background and Aims Acute biliary pancreatitis (ABP) secondary to gallbladder stones has a rapid onset and swift progression, which can be life threatening in severe cases. However, the mechanism and risk factors for ABP induced by gallbladder stones are not entirely clear at present. Therefore, this study was conducted to investigate the risk factors for ABP in patients with cholecystolithiasis, and to construct a predictive model for the risk of ABP.Methods A total of 503 patients admitted for abdominal pain and diagnosed as cholecystolithiasis from January 2018 to March 2021 were enrolled as study subjects. The general clinical data, laboratory data and the occurrence of ABP of the patients were gathered. The risk factors for ABP were screened by univariate and multivariate analyses. The area under curve (AUC) and best cut-off value of each risk factor were determined by ROC curve analysis. A nomogram predictive model was constructed to quantify patient risk, and its clinical predictive ability was assessed by calibration curve and decision curve analyses.Results Among the 503 patients with cholecystolithiasis, 119 cases (23.66%) developed ABP. In patients with ABP compared with those without ABP, the APACHE Ⅱ score, proportion of cases with abnormal gallbladder size, proportion of cases with multiple gallbladder stones, proportion of cases with common bile duct stones, amylase (AMS), C-reactive protein (CRP), procalcitonin (PCT) and neutrophil to lymphocyte ratio (NLR) were increased (P<0.05), while the gallbladder wall thickness was decreased significantly (all P<0.05). Results of ROC curve analysis showed that the AUC values for APACHE Ⅱ score, gallbladder wall thickness, AMS, CRP, PCT and NLR were 0.681, 0.769, 0.886, 0.734, 0.869 and 0.822, and the best cut-off values were 13.89, 1.89 mm, 382.10 U/L, 18.69 mg/L, 5.76 μg/L and 3.05, respectively. Multivariate Logistic regression analysis showed that gallbladder wall thickness (<1.89 mm), multiple gallstones, AMS (≥382.10 U/L), CRP (≥18.69 mg/L), PCT (≥3.68 g/dL) and NLR (≥3.05) were independent risk factors for the occurrence of ABP in patients with cholecystolithiasis (all P<0.05). For the nomogram constructed by integrating the independent risk factors, the C-index was 0.691 (95% CI=0.661-0.735), and risk threshold was 0.14, and the clinical net benefit of the nomogram model was significantly higher than that predicted by any single variable.Conclusion Gallbladder wall thickness, multiple gallstones, AMS, CRP, PCT, and NLR are factors closely related to the occurrence of ABP in patients with gallbladder stones. The nomogram model constructed based on these factors has certain clinical value for early identification and warning of ABP in patients with gallbladder stones.

9 Establishment and evaluation of early biliary infection prediction model after ERCP in malignant biliary obstruction

MA Yongxin , ZHANG Xusheng , LIU Kejun , LIU Yimin , ZHOU Hongcai , WEI Peng , CHEN Bendong

2023, 32(8):1208-1217. DOI: 10.7659/j.issn.1005-6947.2023.08.009

[Abstract](508) [HTML](453) [PDF 1.12 M](921)

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Background and Aims Early biliary infection (EBI), as a common complication after endoscopic retrograde cholangiopancreatography (ERCP) combined with biliary stenting in patients with malignant biliary obstruction (MBO), has a significant impact on the survival time and quality of life of patients, and the current research mainly focuses on the risk factors for biliary tract infections, whereas studies on the risk prediction model for the occurrence of EBI are rare. Therefore, based on preoperative clinical data, this study was conducted to construct a risk prediction model of EBI after ERCP combined with biliary stent placement in MBO patients to reduce the incidence of EBI in patients through early and precise preoperative intervention.Methods The clinical data of 285 patients who underwent ERCP combined with biliary stent placement in the Department of Hepatobiliary Surgery of the General Hospital of Ningxia Medical University from January 2018 to September 2021 were retrospectively analyzed (all patients included were diagnosed with MBO by imaging data or pathological evidence). The study endpoint was biliary infection within 30 d after ERCP. The patients were randomized into modeling and validation groups in a 7∶3 ratio. The data of the modeling group were analyzed by univariate analysis and multivariate Logistic regression analysis to construct a predictive model, and artificial neural network (ANN) was used to evaluate the importance of predictor variables. The model was internally and externally validated, and receiver operating characteristic (ROC) and calibration curves were generated to evaluate and test the model's performance.Results The clinical data of 285 patients were included in this study, with 200 cases assigned to the modeling group and 85 cases to the validation group after randomization. Results from univariate and multivariate analyses indicated that location of obstruction (OR=5.942, 95% CI=2.507-14.081, P<0.001), gallstones (OR=4.821, 95% CI=2.087-11.138, P<0.001), diabetes mellitus (OR=5.407, 95% CI=2.067-14.148, P=0.001), and infarct length (OR=1.058, 95% CI=1.028-1.089, P<0.001) were independent risk factors for EBI in MBO patients after ERCP. Logistic regression models were constructed from the independent risk factors and the models were visualized in the form of a nomogram. The assessment of predictive variable weights using ANN ranked them as follows: obstruction length (46.8%), obstruction location (18.6%), diabetes (18.1%), and gallstones (16.5%). The Logistic model underwent internal and external validation, yielding area under the curve (AUC) values of 0.807 and 0.831 and C-index values of 0.807 and 0.831, respectively. The Hosmer-Lemeshow goodness-of-fit test indicated no significant deviations between predicted and actual values (modeling group: P=0.845, validation group: P=0.197).Conclusion According to the ANN evaluation, the constructed Logistic model effectively predicts the risk of post-ERCP EBI occurrence, with obstruction length being identified as the most crucial predictive variable. This model holds potential value for clinical efforts to prevent EBI occurrences. For high-risk patients who might experience postoperative EBI, relevant preemptive measures should be taken before surgery to mitigate the impact of associated risk factors and minimize the incidence of EBI.

10 Application of laparoscopic anatomic hepatectomy using extra-Glissonean approach combined with ICG fluorescence negative staining in treatment hepatolithiasis (with video)

LIU Ling , XIAO Yao , SHENG Langqing , ZHANG Qi , ZHOU Jixiang , LIU Gang , LI Xiaoli , ZHAI Denggao , LIN Ling , WAN Xiaoping , GONG Liansheng , LI Nianfeng

2023, 32(8):1218-1228. DOI: 10.7659/j.issn.1005-6947.2023.08.010

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Background and Aims Hepatolithiasis is one of the most common digestive system diseases, which can progress to liver cirrhosis, biliary tract infection, liver abscess, and even cholangiocarcinoma. Hepatectomy remains the thorough treatment method for hepatolithiasis. In recent years, with the advancement of technology, laparoscopic surgery has gradually replaced open surgery due to its superiority in short-term therapy effects. However, compared to hepatobiliary tumors, the inflammation, edema, and adhesion caused by hepatobiliary stones make the surgery more difficult. Therefore, it is necessary to find a simple and reliable surgical approach. Recently, with a renewed understanding of liver anatomy, laparoscopic extra-Glissonean anatomic hepatectomy has become widely used in liver tumors, and there have been reports confirming that its combination with indocyanine green (ICG) fluorescence negative staining technique can enhance the efficiency and precision of surgery. However, its application in hepatolithiasis has been rarely reported. Here, the authors summarize and compile their recent experiences applying the extra-Glissonean approach combined with ICG fluorescence-negative staining in treating hepatolithiasis.Methods The clinical data of seven patients with hepatolithiasis treated in the Department of Biliary Surgery of Xiangya Hospital, Central South University, from February 2022 to April 2023, were retrospectively analyzed. Based on the medical history, clinical symptoms, and preoperative imaging data, all patients exhibited indications for liver resection. Six patients underwent left hepatectomy, and one underwent right posterior lobectomy. Intraoperatively, fluorescence laparoscopy was employed. Under low central venous pressure and total hepatic inflow occlusion, anatomical landmarks on the liver surface (including the Arantius plate, cystic plate, umbilical plate, and Glissonean pedicle of the caudate process) and the Laennec's capsule were utilized to dissect the target hepatic pedicle anatomically. After occlusion, ICG was injected into the peripheral veins, resulting in ischemia/resection demarcation lines on the liver surface. Then, an anatomic hepatectomy was completed with intraoperative exposure of the hepatic vein. In some patients, bile duct incision and intraoperative cholangioscopy were additionally performed to enhance stone clearance rates.Results All seven patients successfully underwent liver resection surgery, and postoperative specimens were dissected to examine and confirm the status of the removed stones. Five patients underwent choledocholithotomy and intraoperative choledochoscopy after liver resection. Intraoperative blood loss ranged from 100 to 600 mL, with an average of (314.3±211.6) mL. No severe complications (Clavien-Dindo grade Ⅲ-Ⅳ) occurred. Except for one patient who was hospitalized for 24 d due to postoperative bile leakage and wound infection, the length of postoperative hospital stay in the remaining patients ranged from 7 to 9 d, with an average of (8.5±0.8) d. Postoperative abdominal ultrasonography, T-tube cholangiography, or MRCP examination revealed complete stone clearance in 6 patients, and in 1 patient, the stones were completely removed after an additional postoperative choledochoscopic lithotomy. Pathological examination results for all cases indicated hepatolithiasis and cholangitis, with no evidence of canceration.Conclusion The application of laparoscopic extra-Glissonean anatomic hepatectomy combined with ICG fluorescence-negative staining in patients with hepatolithiasis is safe and feasible. Its effectiveness and superiority still require further validation through controlled studies with expanded sample sizes and enriched clinical data.

11 Application of indocyanine green fluorescence imaging in laparoscopic reoperation of the biliary tract

HUANG Jie , XU Dingwei , LI Xincheng , LI Ao , ZHANG Yan , HU Manqin

2023, 32(8):1229-1236. DOI: 10.7659/j.issn.1005-6947.2023.08.011

[Abstract](745) [HTML](523) [PDF 911.79 K](1015)

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Background and Aims Compared to intraoperative cholangiography, the indocyanine green (ICG) fluorescence imaging technique offers the advantages of convenient operation and more precise visualization of intraoperative bile ducts. Foreign studies have confirmed the feasibility and safety of the ICG fluorescence imaging technique. However, there are few reports on applying the ICG fluorescence imaging technique in our country's laparoscopic reoperation of the biliary tract. Therefore, this article reports the authors' preliminary experience in applying the ICG fluorescence imaging technique in laparoscopic reoperation of the biliary tract to assess its clinical value.Methods The clinical data of patients who underwent elective reoperation of the biliary tract in the Second Affiliated Hospital of Kunming Medical University from January 2020 to June 2022 were retrospectively collected according to inclusion and exclusion criteria. Patients who underwent the ICG fluorescence imaging technique during surgery were assigned to the observation group, while those who did not receive this technique were assigned to the control group. Patients in the observation group received a 2 mL (total dose 5 mg) intravenous injection of ICG solution 60 min before the start of surgery, and intraoperative three-dimensional imaging of the bile ducts was performed using near-infrared light.Results A total of 184 patients were included, with 80 in the observation group and 104 in the control group. The success rate of the observed bile duct ICG fluorescence imaging system was 93.75% (75/80). The average bile duct identification time during surgery was significantly shorter in the observation group than in the control group (25 min vs. 39 min, P<0.05). In contrast, other intraoperative variables (surgical approach, operative time, intraoperative blood loss, rate of conversion to open surgery) showed no statistically significant differences between the two groups (all P>0.05). The two groups had no significant differences regarding postoperative ventilation time, bile leakage rate, Clavien-Dindo grade of postoperative complications, and stone recurrence rate at 6 months postoperatively (all P>0.05). However, the observation group had a significantly shorter average hospital stay length than the control group (7.13 d vs. 10.35 d, P=0.032).Conclusion The ICG fluorescence imaging technique in laparoscopic reoperation of the biliary tract enables visualization of the biliary system, which can help avoid inadvertent damage due to poor identification of the bile ducts during surgery. This technique ensures safety in reoperative biliary surgery and holds promising potential for clinical application.

12 Rationally considering gallbladder-preserving surgery from historical and developmental perspectives: reflections on the controversies between gallbladder-preservation and cholecystectomy

LU Wencai

2023, 32(8):1237-1245. DOI: 10.7659/j.issn.1005-6947.2023.08.012

[Abstract](483) [HTML](804) [PDF 836.42 K](1082)

Abstract:
Cholecystectomy has become the standard treatment for gallbladder stones and other benign gallbladder diseases because of its efficacy. However, ensuring the effectiveness of surgical treatment, minimizing the trauma and functional loss to patients, and reducing the impact on their postoperative quality of life is the common expectation and pursuits of patients and surgeons. In the 1980s, surgeons at home and abroad used intracystic lithotripsy and indwelling drainage tube to carry out bile-sparing surgery, which has been called the old type of gallbladder-preserving surgery. However, the controversies surrounding it eventually subsided, due to the limitations such as a high postoperative recurrence rate of stones. In 1992, Prof. Zhang Baoshan adopted the choledochoscopy to carry out biliary surgery, giving up the way of intracystic lithotripsy and indwelling drainage tube and focusing on the observation and operation under the direct vision of choledochoscopy, which effectively avoids the residual stones and greatly reduces the recurrence rate of postoperative stones, which is called the new type of gallbladder-preserving surgery. Since the introduction of the new surgical type, it has always been accompanied by controversy, and the focus of the debate is still the recurrence of stones and the gallbladder after biliary lithotripsy as a risk factor for gallbladder cancer has also become the focus of controversy. Arguments and discussion always be the companion of scientific development, which helps to clarify understanding, promote communication and cooperation among scholars with different viewpoints, and promote the progress of science. Reviewing the literature and combining personal experience, the author aims to discuss and analyze the controversies in biliary conservation surgery.

13 Differences in perioperative management between patients with hepatolithiasis-associated and nonhepatolithiasis-associated intrahepatic cholangiocarcinoma undergoing hepatectomy

TU Zhijian , CAO Hui , LI Qian , TANG Weiping , CHEN Guodong

2023, 32(8):1246-1254. DOI: 10.7659/j.issn.1005-6947.2023.08.013

[Abstract](771) [HTML](554) [PDF 753.79 K](947)

Abstract:
Hepatolithiasis is a type of lithiasis that occurs above the confluence of the left and right hepatic ducts. This condition can cause bile duct obstruction and stasis, increasing the likelihood of stone formation. Mechanical obstruction and recurrent inflammatory stimuli can exacerbate bile duct blockage, leading to severe complications such as cholangitis, liver atrophy, cirrhosis, and even the development of cholangiocarcinoma. Intrahepatic cholangiocarcinoma (ICC) is a common malignant liver tumor originating from the intrahepatic bile duct epithelium. It is characterized by high malignancy, low surgical cure rate, high postoperative recurrence rate, and poor prognosis, making it a significant public health concern. The etiology of ICC is still unclear, but numerous studies have indicated that hepatolithiasis is one of the high-risk factors for ICC. Prolonged mechanical and chronic inflammatory stimuli from stones can lead to the development of the bile duct epithelium along the direction of hyperplasia, atypical hyperplasia, and precancerous lesions, eventually evolving into ICC. Based on the degree of association between pathogenic factors and hepatolithiasis, ICC can be classified into hepatolithiasis-related intrahepatic cholangiocarcinoma (HICC) and non-hepatolithiasis-related intrahepatic cholangiocarcinoma (NHICC). Surgical intervention remains the primary treatment for ICC, and early radical hepatectomy can effectively improve the overall survival rate and prognosis of ICC patients. As an area with a high incidence of hepatolithiasis, the incidence of HICC in our country has also been increasing in recent years. Therefore, comprehensive management of HICC is of significant clinical importance. Given the above background, this article focuses on HICC and summarizes the differences in perioperative management between HICC and NHICC. The aim is to provide individualized and precise perioperative management for HICC patients throughout the hepatectomy period to improve the diagnostic rate, provide accurate treatment, accelerate recovery, and enhance the prognosis.

14 Clinical application and research progress of photodynamic therapy in extrahepatic cholangiocarcinoma

QU Yong , CAO Juanmei , GONG Bo , LI Min

2023, 32(8):1255-1263. DOI: 10.7659/j.issn.1005-6947.2023.08.014

[Abstract](469) [HTML](241) [PDF 786.87 K](1137)

Abstract:
Extrahepatic cholangiocarcinoma (eCCA) is a highly aggressive malignant tumor originating from the epithelial cells of the extrahepatic bile duct. Surgical resection with negative margins (R₀) is the most optimal treatment for eCCA patients. However, most patients have already lost the opportunity for radical surgical treatment at the time of initial diagnosis. Currently, palliative therapies such as radiation and chemotherapy yield poor results and come with significant adverse reactions. While biliary stenting, immunotherapy, and targeted therapy have particular efficacy, they also have limitations. Photodynamic therapy, as an emerging minimally invasive interdisciplinary technique with good tolerability and minimal side effects, not only inhibits tumor growth but also, in combination with various treatment modalities, enhances the survival and quality of life for unresectable eCCA patients. Therefore, it holds promising clinical prospects. This article mainly summarizes the mechanisms of photodynamic therapy, the current application status of light sources and photosensitizers, and combined treatments in clinical practice. Additionally, potential strategies to address the current clinical challenges of photodynamic therapy in treating eCCA are proposed to provide a basis and reference for clinical treatment options for eCCA patients and its research directions.

15 Advances in surgical treatment of hilar cholangiocarcinoma

YANG Jinghong , YE Lin , YU Yaqun

2023, 32(8):1264-1270. DOI: 10.7659/j.issn.1005-6947.2023.08.015

[Abstract](347) [HTML](399) [PDF 719.21 K](764)

Abstract:
Hilar cholangiocarcinoma (HCCA) is a malignant tumor that originates from the epithelial cells of the bile ducts, occurring in the left or right hepatic duct, the hepatic duct confluence region, or the proximal segment of the common hepatic duct. Its complex pathogenesis, insidious onset of symptoms, and special anatomical location lead to most patients being diagnosed at an advanced stage, making it a challenging aspect of clinical diagnosis and treatment. Only about 20% of patients can receive radical resection, with a R₀ resection rate ranging from 50% to 92%. The postoperative recurrence rate is high, and the prognosis is generally poor, with 5-year survival rates ranging from only 10% to 42%. Currently, surgical resection remains the main approach to improve the prognosis. With advancements in various surgical techniques, some progress has been made in the surgical treatment of HCCA, but it still faces numerous challenges. In this review, the authors provide an overview of the latest research progress and related controversies concerning the surgical treatment of HCCA.

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Volume 32,Issue 8,2023 Table of Contents

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