Volume 31,Issue 8,2022 Table of Contents

1 Meta-analysis of the optimal resection scope of hepatectomy for T2 gallbladder carcinoma

ZHU Jiahai , SHAO Hanrui , WANG Xinyue , YI Xiaotian , ZHAO Songling , ZHU Ya , ZOU Hao

2022, 31(8):987-996. DOI: 10.7659/j.issn.1005-6947.2022.08.001

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Background and Aims Gallbladder carcinoma (GBC) is the most common malignant tumor of the biliary system, accounting for 80%-95% of biliary malignancies worldwide, and has a poor prognosis with a 5-year overall survival (OS) rate of only 10%-25%. At present, radical resection is the only possible way to cure GBC, but the recommended scopes of hepatic resection for T2 GBC are different in different guidelines. Therefore, this study was conducted to systematically evaluate the optimal scope of hepatectomy for T2 GBC.Methods Computer retrieval was performed in PubMed, Embase, Web of science, Cochrane Library, China Biology Medicine disc (CBMdisc), China National Knowledge Infrastructure (CNKI), Wanfang Database and VIP Database according to the inclusion and exclusion criteria, and the quality of eligible literature was assessed by the Newcastle-Ottawa Scale. RevMan version 5.4 software was used to analysis the difference of 1-, 3-, 5-year OS rate of patients of each group.Results Finally, 8 papers were selected, all included stage T2 GBC, and two of which included stage T2a and T2b GBC. Meta-analysis results showed that there was no difference in R₀ and R₁ section of stage T2 GBC between the wedge liver resection with at least a 2-cm margin from the gallbladder bed and liver segment Ⅳb+V resection in 1-, 3-, and 5-year OS rate (OR=0.70, 95% CI=0.45-1.09, P=0.12; OR=1.10, 95% CI=0.79-1.53, P=0.58; OR=1.18, 95% CI=0.89-1.56, P=0.25). There was no significant difference in 1- and 5-year OS rates for R₀ resection (OR=0.84, 95% CI=0.49-1.44, P=0.53; OR=0.89, 95% CI=0.64-1.25, P=0.51), while the 3-year OS rate was significantly different (OR=1.46, 95% CI=1.03-2.07, P=0.03). There was no significant difference in the 5-year OS rate of R₀ section of stage T2a and stage T2b GBC with liver tissue resection with at least a 2-cm margin from the gallbladder bed and the liver segment Ⅳb+V resection (OR=0.55, 95% CI = 0.18-1.64, P=0.28; OR=0.99, 95% CI =0.49-2.00, P=0.97).Conclusions Both liver tissue resection with at least a 2-cm margin from the gallbladder bed and the liver segment Ⅳb+V resection can be performed to achieve R₀ resection for stage T2 GBC.

2 Analysis of prognostic value of surgical treatment in patients with small cell carcinoma of gallbladder based on SEER database

HUANG Kun , HE Yunsheng , ZHANG Hongmei , HUANG Zhenghong , YUAN Xinzhu , ZHAO Pan , LI Jianbo , ZHAO Pingwu

2022, 31(8):997-1005. DOI: 10.7659/j.issn.1005-6947.2022.08.002

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Background and Aims Small cell carcinoma of the gallbladder (SCCG) is a rare neuroendocrine carcinoma. At present, there is a lack of evidence of clinical research with large sample size for this group of patients, and also the prognostic value of surgical treatment is still unclear. The purpose of this study was to evaluate the prognostic value of surgical treatment in SCCG.Methods The clinical data of patients with pathologically diagnosed SCCG from 2000 to 2018 were extracted from SEER database. According to the inclusion and exclusion criteria, a total of 116 cases were included after strictly screening. The patients were divided into operation group and non-operation group according to whether they received surgery or not. The differences in cancer-specific survival (CSS) and overall survival (OS) between the two groups were compared, and the influencing factors for CSS and OS were analyzed.Results The median age of the included patients was 64 years old (IQR: 54-75 years), and 30.17% (35/116) of patients were men. There were 63 cases (54.31%) in the operation group and 53 cases (45.69%) in the non-operation group. The median follow-up was 9 months (IQR: 3-19.5 months). Of the 63 patients in the operation group, 45 died (71.43%), including 42 tumor-related deaths (66.67%). Of the 53 patients in the non-operative group, 48 died (90.57%), including 44 tumor-related deaths (83.02%). The estimated 1-year OS of operation group and non-operation group were 62.40% and 23.70%, and the estimated 1-year CSS of operation group and non-operation group were 64.81% and 26.08%, respectively. There were significant differences between the two groups (χ²=19.75 and χ²=8.53, both P<0.001). Results of multivariate prognostic analysis by Cox proportional hazard mode showed that age, presence or absence of hepatic metastasis, receiving surgical treatment or not, and receiving radiotherapy or not were independent influencing factors for OS, and presence or absence of hepatic metastasis, receiving surgical treatment or not, and receiving radiotherapy or not were independent influencing factors for CSS (all P<0.05). The OS (HR=0.54, 95% CI=0.33-0.89, P=0.017) and CSS (HR=0.52, 95% CI=0.31-0.87, P=0.014) in SCCG patients were significantly improved by surgical treatment. Stratified analyses based on clinicopathologic characteristics showed that surgical treatment significantly improved the OS in patients with age <60 years (HR=0.14, 95% CI=0.05-0.38, P<0.001), female sex (HR=0.45, 95% CI=0.25-0.81, P=0.008), unmarried status (HR=0.41, 95% CI=0.17-0.94, P=0.037), and no presence of hepatic metastasis (HR=0.16, 95% CI=0.04-0.67, P=0.012), or patients not receiving radiotherapy (HR=0.56, 95% CI=0.32-0.96, P=0.037), and undergoing chemotherapy (HR=0.33, 95% CI=0.17-0.63, P<0.001); surgical treatment significantly improved the CSS in patients with age <60 years (HR=0.14, 95% CI=0.05-0.38), P<0.001), female sex (HR=0.43, 95% CI=0.23-0.80, P=0.008), unmarried status (HR=0.31, 95% CI=0.12-0.79, P=0.013), and no presence of hepatic metastasis (HR=0.13, 95% CI=0.02-0.69, P=0.017), or patients not receiving radiotherapy (HR=0.51, 95% CI=0.29-0.90, P=0.022),and undergoing chemotherapy (HR=0.35, 95% CI=0.18-0.67, P=0.002).Conclusion Surgical treatment can improve the OS and CSS in SCCG patients, especially in those with age <60 years, female sex, unmarried status, and without hepatic metastasis or radiotherapy, or having chemotherapy.

3 Analysis of factors affecting postoperative survival of patients with cholangiocarcinoma in different histological sites

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

2022, 31(8):1006-1016. DOI: 10.7659/j.issn.1005-6947.2022.08.003

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Background and Aims At present, surgical resection is still the preferred treatment choice for cholangiocarcinoma (CCA), but the postoperative recurrence rate is high and the survival rate of patients is low. The determination of influencing factors for postoperative survival of CCA patients may be helpful for optimizing surgical planning, and thereby, to a certain extent improving the prognosis of the patients. Therefore, this study was conducted to investigate the factors influencing the postoperative survival of patients with CCA arising from different histological sites, so as to provide reference for clinical treatment.Methods The clinicopathologic data of 133 patients with CCA undergoing surgical treatment from January 2011 to March 2020 were retrospectively analyzed. There were 58 patients with intrahepatic cholangiocarcinoma (iCCA), 30 patients with hilar cholangiocarcinoma (hCCA), and 45 patients with distal cholangiocarcinoma (dCCA). The relations of the clinicopathologic characteristics with the postoperative survival of patients were analyzed and the prognostic factors were determined.Results For iCCA patients, the 1-, 2-, 3- and 5-year survival rates were 41.38%, 22.41%, 8.62% and 3.45%, respectively. Univariate analysis showed that the concomitant bile duct stones, preoperative serum albumin (ALB) level, thrombin time, levels of CEA, CA125 and CA19-9, Child-Pugh grade, the maximum diameter of the mass, whether or not R₀ resection was achieved, lymph node metastasis and the histological grade were associated with the postoperative survival of iCCA patients (all P<0.05); multivariate analysis showed that the preoperative ALB level, thrombin time, CA19-9, Child-Pugh grade, maximum diameter of tumor and whether or not R₀ resection was achieved were independent influencing factors for the postoperative survival of iCCA patients (all P<0.05). For patients with hCCA, the 1-, 2-, 3- and 5-year survival rates were 43.33%, 20.0%, 6.67% and 3.33%, respectively. Univariate analysis showed that the preoperative CEA level, whether or not R₀ resection was achieved, presence of lymph node metastasis, degree of differentiation of the tumor, the maximum diameter of the mass and presence of the portal vein invasion were related to the postoperative survival of hCCA patients (all P<0.05); multivariate analysis showed that whether or not R₀resection was achieved, presence of lymph node metastasis, histological grade, portal vein invasion and maximum diameter of tumor were independent influencing factors for the postoperative survival of hCCA patients (all P<0.05). For patients with dCCA, the 1-, 2-, 3- and 5-year survival rates were 62.22%, 31.11%, 17.78% and 14.29, respectively. Univariate analysis showed that the lymph node metastasis and histological grade were associated with the postoperative survival of dCCA patients (all P<0.05), multivariate analysis showed that the lymph node metastasis, histological grade and whether or not R₀ resection was achieved were independent influencing factors for the postoperative survival of dCCA patients (all P<0.05).Conclusion There are generally common prognostic factors for CCA arising from different histological sites. Evaluation of these factors may helpful for estimating the prognosis of CCA, improving the stratification standard of CCA patients, optimizing the preoperative and postoperative treatment of CCA patients, and lengthening the survival time.

4 Comparison of the application of T-tube or double J-tube drainage and primary duct closure in laparoscopic common bile duct exploration

YU Henghai , WEI Xiaoping

2022, 31(8):1017-1023. DOI: 10.7659/j.issn.1005-6947.2022.08.004

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Background and Aims Laparoscopic common bile duct exploration (LCBDE) has become the main method and even the first-line recommended procedure for the treatment of common bile duct stones because of its clinical advantages of small trauma and rapid recovery. However, whether bile drainage is required after LCBDE and the choice of different bile drainage methods are still controversial, such as the discussion of the indications of traditional LCBDE plus external biliary drainage tube (T-tube), whether the primary suture alone leads to high incidence rate of postoperative complications, and whether the internal biliary drainage (double J-tube) is superior to T-tube. To solve the problem mentioned above, this study was conducted to compare the clinical application of T-tube drainage, double J-tube drainage and primary duct closure (PDC) in LCBDE through a retrospective method, and discuss their indications.Methods The clinical data of 363 patients undergoing LCBDE in the Second Affiliated Hospital of Kunming Medical University from March 2015 to May 2018 were retrospectively collected. The patients were divided into T-tube group (128 cases), double J-tube group (115 cases) and PDC group (120 cases) according to the treatment method used. The preoperative general data (sex, liver function, diameter of the common bile duct, and stone size), perioperative variables (operation time, postoperative hospital stays, and hospitalization cost), and incidence of postoperative complications (biliary pancreatitis, bile leakage, biliary stricture, tube detachment, and residual stones) were compared among the three groups.Results There were no significant differences in the preoperative general data among the three groups of patients (all P>0.05). The average operative time in PDC group (75.5 min) was shorter than that in T-tube group (98.5 min) or double J-tube group (90.5 min), the average length of hospital stay in PDC group (4.8 d) or double J-tube group (5.4 d) was shorter than that in T-tube group (7.8 d), and the average medical cost in PDC group (18 489 yuan) or double J-tube group (20 157 yuan) was less than that in T-tube group (24 034 yuan). All the differences had statistical significance (all P<0.05). There was no significant difference in the overall incidence of complications among the three groups (P=0.521), but the incidence rate of biliary leakage in PDC group (3.3%) was higher than those in the other two groups (both P<0.05), and all the patients had multiple bile duct stones (>1 stone), of whom, 3 cases had incarcerated calculus of the sphincter of Oddi, and the diameter of the common bile duct in 2 cases was less than 10 mm; the incidence rate of postoperative pancreatitis in double J-tube group (4.3%) was higher than those in the other two groups (both P<0.05), and the causes included duodenal papillary edema were caused by incarcerated stones in 2 cases, juxta-papillary duodenal diverticula in 2 cases, and inflammatory papillary stenosis in 1 case.Conclusion Although the PDC has some advantages in terms of length of hospital stay and cost of hospitalization, the incidence of postoperative complications is higher, and T-tube drainage and double J-tube drainage also have their own advantages and indications. The necessity of drainage and drainage method selection should be considered based on the patient's economic situation, combined with a comprehensive judgment on the biliary tract conditions by preoperative examination, intraoperative laparoscopy and choledochoscopy, so as to make an "individualized" determination, minimize the postoperative complications and improve patients' satisfaction.

5 Analysis of risk factors for intraabdominal infections in patients after partial hepatectomy for hepatolithiasis

YANG Jieyu , LU Zhilin , LIN Yikun

2022, 31(8):1024-1030. DOI: 10.7659/j.issn.1005-6947.2022.08.005

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Background and Aims Intraabdominal infections are common complications in patients after partial hepatectomy for hepatolithiasis, which will increase patient pain and treatment costs, prolong hospital stays, and even cause life-threatening infectious shock. This study was performed to determine the risk factors for the occurrence of intraabdominal infections after partial hepatectomy in such patients through a retrospective analysis, so as to provide a basis for the prevention of postoperative intraabdominal infections.Methods The clinical data of 54 patients with hepatolithiasis undergoing partial hepatectomy in the Hospital of the Marine Corps of PLA from March 2017 to February 2021 were retrospectively analyzed. A univariate analysis was performed on the factors that may affect the occurrence of postoperative intraabdominal infections, and then the factors with statistical significance were further identified by multivariate Logistic regression analysis.Results Of the 54 patients, postoperative intraabdominal infections occurred in 8 cases (14.8%), and none of them required a re-operation, and all were cured. Univariate analysis showed that the age ≥60 years (χ²=7.091, P=0.008), the preoperative serum albumin (ALB) level <35 g/L (χ²=7.858, P=0.005), and the fluid volume of the surgical field flush <2 L (χ²=6.291, P=0.012) were associated with the occurrence of postoperative intraabdominal infections; further Logistic regression analysis revealed that the advanced age (P=0.025), low preoperative ALB level (P=0.044), and low fluid volume of the surgical field flush (P=0.019) were independent risk factors for the development of postoperative intraabdominal infections.Conclusion The incidence of intraabdominal infections is relatively high after partial hepatectomy for hepatolithiasis. The advanced age (≥ 60 years), low preoperative ALB level (<35 g/L) and insufficient the amount of the surgical field flush (<2 L) are the independent risk factors for the occurrence of postoperative intraabdominal infections. Thus, improving the preoperative ALB level and adequate intraoperative surgical field flush are helpful for preventing the occurrence of intraabdominal infections.

6 Application of indocyanine green fluorescent navigation in laparoscopic cholecystectomy for type I Mirizzi syndrome

WANG Yunfeng , CUN Dongyun , HUANG Jie , TIAN Daguang

2022, 31(8):1031-1038. DOI: 10.7659/j.issn.1005-6947.2022.08.006

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Background and Aims Mirizzi syndrome (MS) is a rare complication of cholecystitis and chronic cholelithiasis. With the development of minimally invasive techniques, laparoscopic cholecystectomy (LC) is increasingly being used for the treatment of type I MS, in which, the intraoperative biliary tract injury is still the most serious complication. At present, indocyanine green (ICG) fluorescent navigation technique is more and more widely being used in the clinical practice of laparoscopic hepatobiliary surgery. This technique can well display the drainage area of the hepatic portal vein and play an important role in anatomical liver resection. During metabolism, ICG is taken up by hepatocytes and excreted into bile and thereby delivered into the duodenum through the biliary tract, which can guide and trace the anatomical structure of the entire biliary tract system. Therefore, this study was performed to investigate the efficacy of ICG in identification and navigation of biliary tract during LC for type I MS.Methods The clinical data of 67 patients with type I MS undergoing LC in the Second Affiliated Hospital of Kunming Medical University from October 2019 to January 2022 were retrospectively analyzed. Of the patients, 35 cases underwent LC under the guidance of intraoperative fluorescence navigation using ICG (fluorescence navigation group), and 32 cases underwent conventional LC (conventional surgery group). The main clinical variables were compared between the two groups of patients.Results There were no significant differences in preoperative data and laboratory measurements between the two groups of patients (all P>0.05). In fluorescence navigation group compared with conventional surgery group, the mean operative time (74.66 min vs. 93.03 min), mean intraoperative blood loss (20.43 mL vs. 57.34 mL) and open conversion rate (0 vs. 12.5%) were significantly reduced; the average drainage volume on postoperative day 1 （25.43 mL vs. 36.63 mL）, average time to tube removal (1.29 d vs. 1.91 d), average length of postoperative hospital stay (2.8 d vs. 3.66 d) and average total hospitalization cost (11 349.43 yuan vs. 12 907.41 yuan) were significantly decreased (all P<0.05). After operation, abdominal wound infection occurred in 2 cases in fluorescence navigation group, while biliary tract injury occurred in 2 cases, bile leakage occurred in 2 cases, and abdominal wound infection occurred in 4 cases in conventional surgery group. The overall incidence rate of postoperative complications in fluorescence navigation group was significantly lower than that in conventional surgery group (5.7% vs. 25.0%, P=0.039).Conclusion ICG fluorescent navigation can display biliary tract system in real time, reduce intraoperative bleeding, operative time, conversion to open surgery and incidence of complications, and prevent biliary tract injury.

7 Expression of long non-coding RNA MCM3AP-AS1 in cholangiocarcinoma cells and its function

LI Bo , ZHAO Qiangzi , LI Jianjun

2022, 31(8):1039-1047. DOI: 10.7659/j.issn.1005-6947.2022.08.007

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Background and Aims Long non-coding RNA MCM3AP-AS1 (MCM3AP-AS1) plays an oncogene function in various tumors such as primary liver cancer, breast cancer and glioblastoma. However, the expression, function and mechanism of MCM3AP-AS1 in cholangiocarcinoma are still poorly understood. Therefore, this study was conducted to observe the expression of MCM3AP-AS1 in cholangiocarcinoma cells and its effect on cell proliferation and invasion, and preliminarily investigate the underlying mechanism.Methods The expressions of MCM3AP-AS1 in cholangiocarcinoma cell lines (CCLP, RBE, 9810, HuCCT1) and human intrahepatic bile duct epithelial cell line (HIBEC) were detected by qRT-PCR. In cholangiocarcinoma cells after transfection with MCM3AP-AS1 siRNA, using cholangiocarcinoma cells transfected with scrambled sequences as negative control, the changes in proliferative and invasion abilities were determined by MTT assay and Transwell assay, and the changes in expressions of the proteins associated with the JAK/STAT3 signaling pathway and epithelial-mesenchymal transition (EMT) process were determined by Western blot. Finally, functional rescue experiment was performed using the JAK/STAT3 pathway agonist leukemia inhibitory factor (LIF) for validation.Results The expressions of MCM3AP-AS1 in all cholangiocarcinoma cell lines were significantly higher than that in HIBEC (all P<0.05). In CCLP cells after transfection with MCM3AP-AS1 siRNA compared with negative control, the proliferative and invasion abilities were significantly decreased (both P<0.05); the expression levels of JAK1/2 and STAT3 showed no significant changes (both P>0.05), but the expression levels of p-JAK1/2 and p-STAT3 were significantly decreased (both P<0.05), and meanwhile, the expression of EMT-related protein E-cadherin was increased and vimentin was decreased (both P<0.05). The results of functional rescue experiment showed that the effects of MCM3AP-AS1 silencing on CCLP cells were all abolished by simultaneous addition of LIF, and all parameters had no significant differences with those in negative control group (all P>0.05).Conclusion The expression MCM3AP-AS1 is up-regulated in cholangiocarcinoma cells, and it promotes the cell proliferation and invasion of the cholangiocarcinoma cells probably through activating the JAK/STAT3 signaling pathway and EMT process.

8 Screening and analysis of key genes in differential expression gene profile of intrahepatic cholangiocarcinoma based on bioinformatics

CHEN Weiyi , CHEN Lijun

2022, 31(8):1048-1063. DOI: 10.7659/j.issn.1005-6947.2022.08.008

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Background and Aims Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor arising from the intrahepatic bile duct epithelium, which has an insidious onset and high degree of malignancy. Because there are no obvious clinical symptoms in the early stage of ICC, and most patients have lost the opportunity for surgery at the time of diagnosis, so its prognosis is very poor. Exploration of targets for early diagnosis and treatment of ICC is of great significance. Therefore, this study was conducted to screen the key genes involved in the occurrence and development of ICC.Methods Two ICC transcriptome datasets (GSE107943, GSE119336) were downloaded from the GEO database. The differentially expressed genes were screened by edgeR package of R language, and then these genes underwent GO and KEGG pathway enrichment analysis. The protein-protein interaction (PPI) networks of these genes was constructed by using STRING database, and the key protein regulatory genes were mined by using the MCODE plug-in of Cytoscape. The expressions of key protein regulatory genes in tumor tissues were analyzed and verified by UALCAN and GEPIA databases. UCSC XENA database was used to analyze the expressions of key regulatory genes in generalized carcinoma. TCGA database was used to analyze the co-expression genes of the key regulatory genes. UALCAN and GEPIA databases were used to analyze the relationship between key regulatory genes and patient prognosis, tumor grade, stage and lymphatic metastasis. The correlation between the expressions of the regulatory genes and immune infiltration were calculated using R language GSVA package. The predictive abilities of the key protein regulatory genes to ICC were evaluated by drawing ROC curve. Cell experiments were performed to verify the expressions of the key regulatory genes.Results A total of 1 094 common differentially expressed genes were screened, including 567 up-regulated genes and 527 down-regulated genes, which were mainly involved in the process of small molecule catabolism, organic acid biosynthesis, carbon metabolism and so on. Three key genes Polo-like kinase 1（PLK1）, hydroxyacid oxidase 2（HAO2）and ficolin-2（FCN2） were mined through PPI networks. PLK1 gene was significantly up-regulated in tumor tissues, and HAO2 and FCN2 genes were significantly down-regulated in tumor tissues, which were verified by UALCAN and GEPIA databases. The analysis of UCSC XENA database showed that the expression of PLK1 was significantly increased in 28 types of tumors, the expression of HAO2 was significantly decreased in 24 types of tumors, and the expression of FCN2 was significantly decreased in 27 types of tumors. The analysis of TCGA database showed that PLK1 was co-expressed with CCNA2 and GTSE1, HAO2 was co-expressed with MTTP and CPS1, and FCN2 was co-expressed with FAM99A and GDF2. The analysis of the UALCAN database found that the expression of three genes was related to the stage and grade of the tumor and lymph node metastasis. Among them, high expression of PLK1, low expression of HAO2 and FCN2 were associated with higher tumor stage, worse differentiation and more prone to lymph node metastasis. The correlation analysis found that the expression of PLK1 was significantly positively correlated with the infiltration of Th2 cells, and the expression of FCN2 was significantly negatively correlated with the infiltration of aDC cells. The ROC curve showed that all the three genes could diagnose ICC well, among which HAO2 had the best diagnostic ability. The results of cell experiments showed that the expression of PLK1 was significantly increased, while the expression of HAO2 and FCN2 were significantly decreased in RBE （all P<0.01）.Conclusion LK1, HAO2 and FCN2 may be the key protein regulatory genes involved in the occurrence and progression of ICC. These three genes may probably become new targets for the diagnosis and treatment of ICC.

9 Expression and action of RUNX3 in colorectal cancer and its association with TGF-β/SMAD4 signaling pathway

JIA Guanghui , DING Yibing , ZHAO Yongqiang , GAO Zengrun

2022, 31(8):1064-1070. DOI: 10.7659/j.issn.1005-6947.2022.08.009

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Background and Aims The transforming growth factor β (TGF-β)/SMAD4 signaling pathway plays an important role in the occurrence and development of colorectal cancer. The expression of runt-related transcription factor 3 (RUNX3) was found to be remarkably decreased in colorectal tissues and it may exert tumor-suppressing effects. However, the relationship between the actions of RUNX3 and TGF-β/SMAD4 pathway has not yet been reported. Therefore, this study was conducted to investigate the expressions and effects of RUNX3 and SMAD4 in colorectal cancer tissue, and their mutual relationship.Methods A total of 98 paired samples of colorectal tissue and adjacent normal tissue were collected. The protein expressions of RUNX3 and SMAD4 were detected by Western blot, and the mRNA expression of SMAD4 was detected by qRT-PCR, respectively. The correlation between RUNX3 and SMAD4 expressions were analyzed. Human colorectal cancer SW480 cells were transfected with RUNX3 overexpression plasmid (RUNX3 group), SMAD4 overexpression plasmid (SMAD4 group) and RUNX3 and SMAD4 overexpression plasmid (RUNX3+SMAD4 group) respectively, using SW480 cells transfected with negative control plasmid as control group. In each group of cells, the changes in RUNX3 and SMAD4 expressions were determined by Western blot and qRT-PCR, and the differences in proliferative and invasion abilities were examined by CCK-8 assay and Transwell assay, respectively.Results The protein expression level of RUNX3 in colorectal cancer tissue was significantly lower than that in adjacent normal tissue, and the mRNA and protein expression levels of SMAD4 were significantly higher in colorectal cancer tissue than those in adjacent normal tissue (all P<0.05); RUNX3 protein expression was negatively correlated with SMAD4 mRNA and protein expressions in colorectal cancer tissue (r=0.511, P=0.004; r=0.487, P=0.009). Compared with control group, the RUNX3 protein expression was significantly increased, while the mRNA and protein expressions of SMAD4 were significantly decreased in the RUNX3 group (all P<0.05); the RUNX3 protein expression showed no significant change (P>0.05), while the mRNA and protein expressions SMAD4 were significantly increased in SMAD4 group (all P<0.05); the RUNX3 protein expression was significantly increased (P<0.05), while the mRNA and protein expressions SMAD4 showed no significant changes in RUNX3+SMAD4 group (both P>0.05). The cell proliferation and invasion abilities were significantly lower in RUNX3 group and were significantly higher in SMAD4 group than those in control group (all P<0.05); both cell proliferation and invasion abilities in RUNX3+SMAD4 represented an intermediate state between RUNX3 group and SMAD4 group, which showed no significant differences with control group (both P>0.05).Conclusion The expression of RUNX3 is down-regulated in colorectal cancer tissue. RUNX3 up-regulation can suppress the malignant biological behavior of colorectal cancer cells, and the mechanism may be associated with its inhibiting the activity of the TGF-β/SMAD4 signaling pathway.

10 Efficacy analysis of surgical treatment for patients with colorectal cancer and simultaneous liver and lung metastases

WANG Lijun , WANG Hongwei , JIN Kemin , LIU Wei , BAO Quan , WANG Kun , XING Baocai

2022, 31(8):1071-1079. DOI: 10.7659/j.issn.1005-6947.2022.08.010

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Background and Aims For colorectal cancer patients with and liver metastases and resectable lung metastases, surgical treatment has been widely accepted as an effective method. However, the treatment strategy for those with unresectable lung metastases still needs to be further specified. Therefore, this study was performed to retrospectively analyze the clinical data of colorectal cancer patients with simultaneous liver and lung metastases treated in the authors' hospital, so as to provide data reference for the treatment of these patients.Methods Using a retrospective cohort method, the data of 127 patients with colorectal cancer and simultaneous liver and lung metastases undergoing surgical treatment in the Department of Hepatopancreatobiliary Surgery Unit I of Peking University Cancer Hospital from January 2008 to December 2020 were collected. Of the patients, all cases underwent complete gross resection (R₀/R₁) of the primary lesions and liver metastases following the principle of tumor radical surgery, and 31 cases received radical local treatment of the lung metastases (local treatment group), while 96 cases did not receive local treatment of the lung metastases (non-local treatment group). The clinical variables, overall survival (OS) and recurrence-free survival (RFS) of the two groups of patients were compared, and the prognostic factors for patients in non-local treatment group were also determined.Results Except that the diameter of the lung metastases in local treatment group was larger than that in non-local treatment group (P<0.05), all other clinical variables showed no significant difference between the two groups (all P>0.05). The median follow-up time for the entire group of patients was 30 (5-134) months, and the rate of lost to follow-up was 3%. For the whole group, the median OS was 41 (4-118) months, and the 1- and 3-year OS rate were 96.8% and 59.7%, in which, the median OS and the 1- and 3-year OS rate were 37 (4-118) months and 95.8% and 51.2% for non-local treatment group, and were 72 (15-101) months, and 100.0% and 82.9% for local treatment group, respectively. The OS was significantly better in local treatment group than that in non-local treatment group (P=0.001). The median RFS was 8 (1-37) months, and the 1- and 3-year RFS rate were 30.8% and 2.4% for non-local treatment group, and the median RFS was 10 (3-67) months, and the 1- and 3-year RFS rate were 38.7% and 18.1% for local treatment group. The RFS was better in local treatment group than that in non-local treatment group, but the difference did not reach a statistical significance (P=0.055). The results of prognostic analysis in the 96 patients in non-local treatment group showed that T4 stage of primary tumor and RAS gene mutations were independent risk factors for OS (both P<0.05), and the median OS in patients with two risk factors were inferior to those with 0 or 1 risk factor (both P<0.05), but their median OS still approached 27 (4-35) months.Conclusion For patients with colorectal cancer and simultaneous liver and lung metastases, surgical resection of the primary lesions and liver metastases combined with local treatment of the lung metastases should be aggressively performed. For patients whose lung metastases cannot be treated locally, irrespective of whether or not they have risk factors, surgical treatment of the primary colorectal cancer and liver metastases may also provide a survival benefit.

11 Clinical efficacy of totally laparoscopic π-shaped esophagojejunostomy following laparoscopic gastrectomy under the enhanced recovery after surgery pathway

GUO Jian , SUN Kang , QU Jianguo , CHEN Jixiang , FAN Xin , XIE Rong , DANG Shengchun , JIN Xi

2022, 31(8):1080-1088. DOI: 10.7659/j.issn.1005-6947.2022.08.011

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Abstract:
Background and Aims Totally laparoscopic π-shaped esophagojejunostomy is a new digestive tract reconstruction method after laparoscopic total gastrectomy. There are a number of studies comparing this method with the conventional laparoscopic-assisted Roux-en-Y esophagojejunostomy under the traditional clinical pathway, but few reports comparing the two methods under the clinical pathway of enhanced recovery after surgery (ERAS). Therefore, this study was conducted to compare the clinical effects of totally laparoscopic π-shaped esophagojejunostomy and laparoscopic-assisted Roux-en-Y esophagojejunostomy following laparoscopic total gastrectomy in ERAS pathway.Methods The clinical data of 65 patients undergoing surgery for gastric cancer from June 2017 to December 2019 were analyzed retrospectively. All patients entered the ERAS pathway and underwent laparoscopic total gastrectomy. Of them, totally laparoscopic π-shaped esophagojejunostomy was used to reconstruct the digestive tract in 30 cases (π-shaped anastomosis group) and laparoscopic-assisted Roux-en-Y esophagojejunostomy was used to restore the digestive tract in 35 cases (Roux-en-Y anastomosis group). The intra- and postoperative variables and follow-up data were compared between the two groups.Results The preoperative date of the two groups were comparable. The incision length, the time to first postoperative ambulation, time to first anal gas passage, time to first food intake, postoperative pain and length of hospitalization in π-shaped anastomosis group were superior to those in anastomosis Roux-en-Y group (all P<0.05). There were no significant differences in operative time, intraoperative blood loss, total number of lymph node dissection, total hospitalization cost and overall incidence of postoperative complications between the two groups (all P>0.05). During postoperative follow-up, different degrees of metastasis and recurrence occurred in 4 patients in π-shaped anastomosis group and 6 patients in Roux-en-Y anastomosis group, and the difference had no statistical significance (P>0.05). The one-year survival rate was 73.33% in π-shaped anastomosis group and 77.14% in Roux-en-Y anastomosis group, and the difference had no statistical significance (P>0.05).Conclusion After laparoscopic gastrectomy, using totally laparoscopic π-shaped esophagojejunostomy has the advantages of small trauma, quick recovery and short hospitalization period, and its advantages can be enhanced with ERAS pathway.

12 Advances in treatment of unresectable hilar cholangiocarcinoma

LI Hao , LI Fazhao , ZHANG Ruizhi , CHEN Ziran , DAI Weidong

2022, 31(8):1089-1101. DOI: 10.7659/j.issn.1005-6947.2022.08.012

[Abstract](964) [HTML](925) [PDF 977.84 K](1379)

Abstract:
Hilar cholangiocarcinoma (hCCA), also known as Klatskin tumor, is a malignant tumor that originates from the biliary epithelium between the secondary hepatic duct and the opening of the cystic duct. Surgery is the only potentially curative treatment for hCCA. The nature of the surgical margins is the most critical factor in the long-term survival of patients undergoing resection. However, as the most common subtype of cholangiocarcinoma, the pathological type of hCCA is mostly low to moderately differentiated adenocarcinoma, which is highly invasive and malignant, with no obvious early symptoms and no effective means of detection, so most patients are already at an advanced stage of the disease at the time of diagnosis and have lost the indication for surgery. Although neoadjuvant chemoradiotherapy combined with in orthotopic liver transplantation has been demonstrated to be an effective treatment modality for some locally advanced unresectable hCCA, it cannot become a treatment option for most patients because of the strict inclusion criteria, shortage of liver sources, and loss of transplantation condition in some patients due to tumor progression while waiting for liver sources. Although conventional chemoradiotherapy prolongs the survival time of patients with unresectable hCCA to some extent, its efficacy remains limited. Some researches have indicated that neoadjuvant chemoradiotherapy can downgrade a previously unresectable hCCA into a resectable one and improve the R₀resection rate, but it lacks credibility because of the limited amount and obsolescence of the relevant data. With the advancement of technology, photodynamic therapy and new radiotherapy techniques including stereotactic radiotherapy, three-dimensional conformal radiotherapy and radioactive particle implantation have emerged, local treatment of hCCA has entered a more precise era. In recent years, with the development of genetic testing and in-depth research on tumor microenvironment, inhibiting tumor progression at the molecular biology level is a popular direction for research on various solid tumors. Targeted drugs for different targets and immune checkpoint inhibitors (PD1/PD-L1 antibodies, CTLA4 antibodies) have emerged and made rapid progress, providing a new direction for the treatment of unresectable hCCA. However, as far as the current research is concerned, although targeted therapy and immunotherapy have achieved excellent results in the treatment of intrahepatic cholangiocarcinoma, their performance in the treatment of hCCA is still unsatisfactory. A single treatment of unresectable hCCA is less effective, the combination of multiple treatment modalities is the focus of current research. This article mainly addresses the progress in the treatment unresectable hCCA and the feasibility of neoadjuvant therapy in achieving R₀ resection, hoping to provide some reference for the treatment of such patients.

13 Research progress of difficult selective biliary cannulation in the first ERCP session

FAN Ling , FU Yan , YE Lei , YANG Yao , LIU Yi

2022, 31(8):1102-1112. DOI: 10.7659/j.issn.1005-6947.2022.08.013

[Abstract](686) [HTML](1023) [PDF 1.32 M](1550)

Abstract:
Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most technically challenging therapeutic endoscopic procedures. The primary condition for successful implementation of ERCP is biliary cannulation, which has a success rate of about 75%-85% with conventional standard biliary cannulation technique, but there is still 8.1% of patients with difficult biliary cannulation. At present, there is no unified international consensus on the definition of difficult cannulation, and most studies define difficult biliary cannulation based on the number of cannulation attempts and/or duration of cannulation. The occurrence of difficult cannulation depends on some uncontrollable factors such as patient anatomy (eg, diverticulum papilla, thick and long duodenal papilla, abnormal confluence of biliopancreatic duct, etc.), disease-specific factors (eg, duodenal papilla or ampulla tumor, biliary lithoyomy after digestive tract reconstruction, etc.), and operators' experience. Difficult cannulation is closely associated with the increase of adverse events after ERCP, of which post-ERCP pancreatitis (PEP) is the most common and serious complication. Therefore, early risk stratification of population with high-risk of PEP is crucial. At present, an increasing number of scholars are attempting to develop clinically practical PEP risk prediction score systems. When difficult intubation is encountered, the overall success rate of bile duct intubation can be increased to 95% by using advanced rescue intubation techniques. The current commonly used rescue intubation techniques based on ERCP mainly include double-guidewire technique, wire-guided cannulation over a pancreatic stent, transpancreatic precut sphincterotomy, needle-knife precut papillotomy, and needle-knife precut fistulotomy. However, these advanced techniques also increase the risk of complications and their implementations are limited by factors such as the anatomical structure of the duodenal papilla, the process of the guidewire insertion into the pancreatic duct, and the skill level of the surgeon. If cannulation still fails despite the use of above-mentioned rescue intubation techniques, the operation should be terminated immediately and a second ERCP should be considered to be performed a few days later, in combination with the measures such as percutaneous transhepatic cholangial drainage, percutaneous transhepatic gallbladder drainage, and the newer endoscopic ultrasound (EUS)-guided interventions, EUS-guided rendezvous or EUS-guided anterograde interventions. The purpose of this paper is to describe the definition, related risk factors and adverse impacts of difficult cannulation, to review and compare the safety and effectiveness of different rescue intubation techniques, and to discuss the selection and application of different rescue intubation techniques from different difficult intubation scenarios. In addition, this article also introduces the alternative measures and the selection basis after the failed cannulation in the first ERCP procedure, so as to provide a reference for the establishment of standardized ERCP intubation procedure in clinical practice.

14 Research progress of intestinal flora in etiology of cholelithiasis

CHENG Meng , NIU Zhiqiang , CHEN Zongkun , ZHANG Haiyang , HUO Chenda , LIU Lixin , WEI Zhigang , LAI Zhiyong , XU Jun

2022, 31(8):1113-1120. DOI: 10.7659/j.issn.1005-6947.2022.08.014

[Abstract](1246) [HTML](653) [PDF 755.25 K](1408)

Abstract:
Cholelithiasis is the most common biliary surgical disease. The clinical symptoms mainly depend on the location of the stones, biliary obstruction, biliary tract infection and other factors, and can be manifested as abdominal pain, fever, nausea, vomiting, jaundice and other features. With the aging of population and the change in dietary pattern, the incidence of this disorder is gradually increasing. Although the diagnosis and treatment technology has been relatively mature, the specific cause and pathogenesis of the formation of biliary stones have not been fully elucidated. Metabolic syndrome related diseases may be closely associated with the formation and development of cholelithiasis. Intestinal dysbacteriosis can induce metabolic changes, and lead to the development of metabolism related diseases. Therefore, cholelithiasis has a close relationship with intestinal microecological imbalance, but the studies on the relationship between intestinal microecological imbalance and occurrence of cholelithiasis are relatively limited, and the action mechanism is still unclear. Here, the authors review the role of intestinal microbiota in the pathogenesis of cholelithiasis, and discuss the future research directions.

15 Research progress of gastric cancer with concomitant sarcopenia

XIAO Haiyan , LIU Ting , LI Dai , TANG Mimi

2022, 31(8):1121-1128. DOI: 10.7659/j.issn.1005-6947.2022.08.015

[Abstract](784) [HTML](350) [PDF 746.37 K](1383)

Abstract:
Sarcopenia is an age-related clinical syndrome caused by loss of skeletal muscle mass and function. The main causes include lack of exercise, weakened neuromuscular function, age-related hormonal changes, and increased levels of inflammatory cytokines. Gastric cancer is one of the most common digestive tract tumors in China, and ranks the second in morbidity and the third in mortality among all cancers, which seriously threatens people's health. A number of studies have shown that gastric cancer with sarcopenia can significantly affect the postoperative state and survival of patients, which is of great significance in predicting the prognosis of gastric cancer. In addition, some drugs and chemotherapy for gastric cancer can lead to chemotherapy-related sarcopenia, which has a negative influence on the treatment outcome of gastric cancer patients. In recent years, the influence of sarcopenia on gastric cancer has attracted increasing attention. Here, the authors address the pathogenesis of sarcopenia, chemotherapy-related sarcopenia, the significance of sarcopenia in predicting the prognosis of gastric cancer, and the treatment and prevention of gastric cancer complicated with concomitant sarcopenia, so as to provide new avenues for development of precise treatment protocols for gastric cancer patients.

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Volume 31,Issue 8,2022 Table of Contents

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