Volume 32,Issue 4,2023 Table of Contents

1 Expert consensus on technical specifications for clinical application of photodynamic therapy for cholangiocarcinoma

2023, 32(4):475-487. DOI: 10.7659/j.issn.1005-6947.2023.04.001

[Abstract](762) [HTML](491) [PDF 1.01 M](1629)

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Photodynamic therapy (PDT) is an effective minimally invasive treatment for tumors, which can be combined with other systemic treatments such as biliary stenting, extrahepatic bile duct drainage, and chemotherapy for the treatment of cholangiocarcinoma. It is mainly suitable for the treatment of unresectable cholangiocarcinoma and adjuvant therapy for postoperative residual or local recurrence of tumors, which can effectively control local tumor progression, relieve biliary obstruction, improve patients' quality of life, prolong survival, and has the advantages of being minimally invasive, precise and repeatable. Currently, there is limited clinical evidence for the use of PDT in cholangiocarcinoma, and there is a lack of clinical technical standards and consensus. The Group of Operative Surgery, Branch of Surgery, Chinese Medical Association, Group of Biliary Surgery, Branch of Surgery, Chinese Medical Association and Chinese Committee of Biliary Surgeons organized relevant experts to discuss the indications, contraindications, technical operation standards, efficacy evaluation, and complications management of PDT, and reached a consensus, aiming to provide a reference for the clinical application of PDT in the treatment of cholangiocarcinoma.

2 Neural network prediction model for assisting diagnosis of microsatellite status in colorectal cancer

HAO Jun , WANG Shuai , ZHU Jun , XU Chunsheng

2023, 32(4):488-496. DOI: 10.7659/j.issn.1005-6947.2023.04.002

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Backgrounds and Aims Microsatellite instability (MSI) has become an important biological marker for clinical diagnosis, adjuvant therapy, and prognostic guidance in colorectal cancer (CRC). Microsatellite instability often accompanies the loss of DNA mismatch repair proteins (dMMR). Currently, the diagnosis of mismatch repair protein deficiency mainly relies on the results of pathological immunohistochemistry for four repair proteins (MLH1, MSH2, MSH6, and PMS2), and MSI has become an important biological marker for immunotherapy in CRC. However, there are few studies on precise MSI prediction models and new signature genes. With the development of artificial intelligence in medicine, precise prediction and data mining have become research hotspots. The aim of this study was to establish a neural network model for MSI prediction and to discern new MSI signature genes.Methods Three CRC GEO datasets (GSE39582, GSE29638, and GSE75315) were used as model training sets, and one TCGA CRC dataset was used as an independent external validation set. Based on the sequencing data and microarray data of the datasets, a neural network prediction model for CRC MSI was established using differential analysis, random forest algorithm, and elastic backpropagation algorithm. Traditional machine learning models for MSI were established using K-nearest neighbor algorithm (KNN) and support vector machine (SVM) algorithm. The prediction ability of the models was evaluated using confusion matrices, receiver operating characteristic (ROC) curves, and the area under the curve (AUC).Results In the training set, a total of 787 cases were included, including 111 cases (14.10%) of microsatellite instability-high (MSI-H) and 676 cases (85.90%) of microsatellite instability-low/microsatellite stability (MSI-L/MSS). In the validation set, 389 cases in the TCGA dataset were finally included, including 67 cases (17.22%) of MSI-H and 322 cases (82.78%) of MSI-L/MSS. One hundred MSI-related genes were identified by differential analysis, including 61 up-regulated genes and 39 down-regulated genes. By combining differential analysis and random forest algorithm, the top 30 most significant MSI-related genes were screened out. Based on the expression matrix of the MSI-related genes, a neural network prediction model was established using 23 gene expression matrices. The model showed accurate prediction ability in both the training set (sensitivity: 0.993, specificity: 0.973, diagnostic coincidence rate: 0.990, AUC: 0.991) and the validation set (sensitivity: 0.950, specificity: 0.828, diagnostic coincidence rate: 0.933, AUC 0.922). Moreover, compared with other machine learning models, the neural network model demonstrated more accurate prediction ability in predicting MSI.Conclusion The neural network prediction model combined with tissue deep sequencing can assist clinicians in diagnosing the MSI status of CRC, and provide references and decision-making basis for the selection of tumor immunotherapy schemes. At the same time, the identified MSI signature genes provide clues and directions for in-depth research on related functions and mechanisms.

3 Short- to mid-term efficacy of robot-assisted versus laparoscopic-assisted right hemicolectomy with complete mesocolic excision for right-sided colon cancer: a single-center and single-surgeon experience

HUANG Bin , TIAN Yue , ZHENG Huichao , TONG Weidong , YAO Hui

2023, 32(4):497-505. DOI: 10.7659/j.issn.1005-6947.2023.04.003

[Abstract](875) [HTML](724) [PDF 767.70 K](1072)

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Background and Aims In the past decade, the concept of complete mesocolic excision (CME) has been further developed in attempt to minimize the recurrence of right-sided colon cancer. Robotic technology can overcome the limitations of laparoscopic surgery, but its clear advantages are still controversial. Therefore, this study further compares the efficacy of robotic and laparoscopic right hemicolectomy with CME for the treatment of right-sided colon cancer.Methods Clinical data of 169 patients with right-sided colon cancer who underwent right hemicolectomy with CME at the Army Medical Center of PLA from July 2016 to December 2021 were retrospectively analyzed. All operations were performed by one surgeon. Among them, 61 cases underwent Da Vinci robotic-assisted right hemicolectomy with CME (robotic group), and 108 cases underwent laparoscopic-assisted right hemicolectomy with CME (laparoscopic group). The main clinical variables of the two groups of patients were compared.Results There was no statistically significant difference in the general preoperative data between the two groups (all P>0.05). There were no cases of perioperative death in either group. The conversion rate during surgery in the robotic group was significantly lower than that in the laparoscopic group (0 vs. 6.5%, P=0.042). The main reasons for conversion in the laparoscopic group were severe abdominal adhesions (4 cases) and large tumors that affected surgical visibility and operation (3 cases). The total operative time in the robotic group was significantly longer than that in the laparoscopic group (221.1 min vs. 186.0 min, P<0.001), and the total treatment cost was significantly higher in the robotic group than in the laparoscopic group (90 371.5 yuan vs. 65 136.3 yuan, P<0.001). There was no statistically significant difference between the two groups in terms of intraoperative blood loss, time to oral intake, time to anal gas passage, length of postoperative hospital stay, incidence of perioperative complications, and postoperative pathological results (all P>0.05). The median follow-up time for the whole group of patients was 31 (1-65) months. There was no statistically significant difference in disease-free survival rate (82.6% vs. 82.8%, P=0.722) or overall survival rate (87.9% vs. 84.3%, P=0.870) between the robotic and laparoscopic groups.Conclusion Robotic-assisted right hemicolectomy with CME is a safe and feasible surgical approach. Compared with traditional laparoscopic surgery, although it may take longer and be more expensive, it may have some advantages in managing severe abdominal adhesions and large tumors.

4 Safety and efficacy of atural orifice robot-assisted transanal total mesorectal excision for low rectal cancer in "difficult pelvic" conditions: a report of 3 cases

HAN Mingyu , WANG Wenxiu , WANG Yuhang , DUAN Xiaofei , ZHANG Hairong , ZHOU Quanbo , ZHANG Qingqing , SUN Weipeng , YUAN Weitang , HU Junhong , LIAN Yugui

2023, 32(4):506-513. DOI: 10.7659/j.issn.1005-6947.2023.04.004

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Background and Aims There is currently a lack of clinical experience in using the natural orifice robot-assisted transanal total mesorectal excision (NOSES R-taTME) approach to treat "difficult pelvic" low rectal cancer. Therefore, this study summarizes and analyzes the clinical data of three patients who underwent this procedure, evaluates short-term results, and aims to provide preliminary experience for clinical practice.Methods The perioperative data and short-term outcomes of three patients with "difficult pelvic" low rectal cancer who underwent NOSES R-taTME treatment at the First Affiliated Hospital of Zhengzhou University from February to May 2022 were retrospectively analyzed.Results All three patients were male, aged 54-59 years, and the BMI was 24-34 kg/m². The distance between the ischial tuberosities was 8.0-9.5 cm, the distance from the tumor to the anal verge was 4-5 cm, and a mesorectal fat area of 23.1-30.7 cm². One patient received neoadjuvant chemotherapy, and two patients had tumors located on the anterior wall of the rectum. The robot docking time was 9-20 min, the transanal operation time was 40-70 min, the total operation time was 200-290 min, the estimated blood loss was 50-100 mL, and the total number of lymph nodes retrieved was 15-20. All three cases achieved R₀ resection, and complete total mesorectal excision grade. Postoperative pathology showed stage I in two cases and stage Ⅲ in one case. The length of postoperative hospital stay was 7-11 d All operations were completed successfully without conversion to open surgery, postoperative complications, or deaths, and there were no unplanned readmissions within 30 d after surgery. During follow-up for 3 months, no anastomotic-related complications were observed, and there was no evidence of tumor recurrence or metastasis.Conclusion The NOSES R-taTME approach is safe and feasible for the treatment of "difficult pelvic" low rectal cancer. However, this conclusion still requires further confirmation through larger prospective studies.

5 Analysis of the incidence and anatomical features of the middle rectal artery through the transanal perspective

GU Lei , JIANG Chunhui , LIU Ye , XU Qing

2023, 32(4):514-519. DOI: 10.7659/j.issn.1005-6947.2023.04.005

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Background and Aims With the promotion of transanal total mesorectal excision (taTME), it is essential to distinguish and re-understand the anatomical landmarks of perirectal vessels and the transanal approach from different angles. This study was performed to analyze the occurrence and anatomical position of the middle rectal artery (MRA) through the transanal perspective, so as to provide theoretical guidance for the transanal operation of taTME.Methods Clinical data of patients who underwent taTME after preoperative MDT discussion in our hospital between January 2018 and June 2021 were collected. The general clinical characteristics of the patients, the detection rate of MRA, and the intraoperative MRA bleeding were analyzed.Results A total of 86 patients who underwent taTME were included for analysis. MRA was found in 61 cases (70.9%) during taTME surgery, including bilateral MRA in 49 cases (57.0%), all of which ran in the lateral ligament of the rectum. During the dissection and separation of the lateral ligament of the rectum, bleeding occurred in 10 cases (16.4%) of the 61 patients with MRA, of whom, 8 cases had bilateral MRA, and 2 cases had unilateral MRA. Among the 10 cases of bleeding, 8 cases were operated by electric hook and 2 cases were operated by ultrasonic knife; bleeding were managed by electrocoagulation or ultrasonic knife in 9 cases, and Hemoloc was used for hemostasis in only 1 case.Conclusion MRA runs in the lateral rectal ligament, and the finding of MRA is more precise through the transanal view. This anatomical location can not only ensure better radical treatment of the tumor but also provide better protection for surrounding normal tissues.

6 Application value of detection of free heme in rectal mucosal secretions for early diagnosis of colorectal cancer

WU Meirong , ZHOU Gang , LI Liang , ZHOU Jianyu , LIN Changwei

2023, 32(4):520-528. DOI: 10.7659/j.issn.1005-6947.2023.04.006

[Abstract](321) [HTML](619) [PDF 783.34 K](1073)

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Background and aims In recent years, free heme (FH) detection has shown good screening performance in malignant tumor screening. However, currently there is limited research on FH detection for colorectal cancer, and the sample sizes are small, with poor representativeness. Therefore, this study was conducted to further evaluate the application value of FH detection in the early diagnosis of colorectal cancer with a relatively large sample size.Methods To analyze the efficacy of FH detection for early diagnosis of colorectal cancer as well as its universality or specificity, all hospitalized patients suspicious for gastrointestinal malignancy who underwent FH detection in rectal mucosal secretions from April 2019 to August 2020 in the Department of Gastrointestinal Surgery at the Third Xiangya Hospital of Central South University and met the inclusion criteria were included in the study. Clinical data of the patients were collected. The patients were classified into five groups: the gastrointestinal group (all patients suspicious for gastric or colorectal cancer), the colorectal group (all patients suspicious for colorectal cancer), the right colon group (patients suspicious for right-sided colon cancer), the left colon group (patients suspicious left-sided colon cancer), and the rectum group (patients suspicious rectal cancer). The diagnostic value of FH detection as well as fecal occult blood test (FOBT), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) alone or in combination with FH detection were compared among the groups of patients.Results A total of 345 patients were included in the study, among whom there were 291 cases suspicious for colorectal cancer and 54 cases suspicious for gastric cancer. The results of FH detection showed that, except for the right colon group, the positive rate of FH detection in malignant tumors of the gastrointestinal group, colorectal group, left colon group, and rectum group was higher than that of benign diseases in the same group (all P<0.05). Using pathological results as the gold standard, the sensitivity of FH detection for diagnosing gastric cancer, colorectal cancer, right colon cancer, left colon cancer, and rectal cancer was 40.72%, 47.49%, 17.39%, 57.89%, and 72.29%, respectively, and the difference was statistically significant (P<0.05); the specificity was 80.65%, 78.57%, 84.62%, 73.33%, and 71.74%, respectively, and the difference was not statistically significant (P>0.05). After excluding the right colon group, the positive rates of FOBT, CEA, and CA19-9 single detection in malignant tumors of the gastrointestinal group, colon group, left colorectal group, and rectum group were higher than those of benign diseases in the respective groups (all P<0.05), but there was no significant difference in sensitivity and specificity among the groups (all P>0.05). Among the various combined tests, FH+FOBT was the best combined test considering both sensitivity and cost-effectiveness. The sensitivity of FH+FOBT for diagnosing gastric cancer, colorectal cancer, left colon cancer, and rectal cancer was 74.86%, 85.42%, 92.45%, and 97.22%, respectively, and the specificity was 64.91%, 57.78%, 57.14%, and 60.00%, respectively.Conclusion The detection results of FH have specificity for the location of tumor development and can be used for early diagnosis of left-sided colon cancer, especially rectal cancer, but have limited value for gastric cancer and right-sided colon cancer. The combination of FH and FOBT detection has advantages such as economy, simplicity, and high sensitivity, and is a better method for early diagnosis of colorectal cancer.

7 Mechanism of Lactobacillus rhamnosus metabolite indole-3-lactate promoting colorectal cancer cell apoptosis through antagonizing the SP3/TNF-α pathway

SHI Huiwen , TAO Xuemei , ZHU Yanpeng

2023, 32(4):529-537. DOI: 10.7659/j.issn.1005-6947.2023.04.007

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Background and Aims As is widely known, the microbiota in the gastrointestinal tract plays an important role in regulating intestinal health. Having a balanced microbiota can help prevent diseases, particularly cancer related to the gastrointestinal system. Lactobacillus rhamnosus (L. rhamnosus) has been found to have anti-tumor effects, but the specific mechanisms are still unclear. Based on this, this study was conducted to investigate the impact and potential mechanisms of L. rhamnosus on apoptosis of human colorectal cancer cells (CRC).Methods Human CRC cells HCT-116, HT-29, and normal colon epithelial cells NCM-460 were treated with the culture supernatant of L. rhamnosus (LRCS) or Escherichia coli (E. coli) culture supernatant (ECCS), and cell viability, apoptosis level, and cell cycle distribution were measured. The bacterial culture supernatant was divided into low molecular weight (<3 kDa) and high molecular weight (>3 kDa) fractions using a 3 kDa ultrafiltration membrane, and the effects of these fractions on cell apoptosis were analyzed. Untargeted LC-MS/MS was used to identify anti-CRC metabolites in the effective fraction of LRCS, and these metabolites were screened at a concentration of 5 μmol/L to identify key metabolites affecting apoptosis. SiRNA screening was performed to identify the target of the key metabolites in the apoptotic pathway. Molecular docking analysis was conducted to study the interaction sites between the key metabolites and the target molecules.Results LRCS exhibited a concentration-dependent decreasing effect on cell viability of CRC cells and significantly promoted apoptosis in CRC cells (all P<0.05), while ECCS had no such effects (all P>0.05). Further analysis revealed that only the low molecular weight fraction of LRCS was capable of producing these effects. Untargeted LC-MS/MS identification and validation experiments indicated that indole-3-lactic acid (I3L) was a key metabolite of L. rhamnosus that influenced CRC apoptosis. Through siRNA screening, I3L showed no significant effect on apoptosis level or TNF-α expression and secretion levels in CRC cells with knockout of the specific protein 3 (SP3) (all P>0.05). Molecular docking revealed that I3L interacted with K551, E551, and E552 of SP3. CRC cells with SP3 knockout were transfected with wild-type SP3 overexpression plasmid and mutant SP3 overexpression plasmid, respectively, and I3L was found to promote cell apoptosis and TNF-α secretion in the former (all P<0.05), but had no effect on those in the latter (all P>0.05).Conclusions L. rhamnosus can promote apoptosis of CRC cells, and the mechanism of action may be related to its metabolite I3L binding to the K551, E551, and E552 sites of SP3, leading to increased transcription and secretion of TNF-α.

8 Expression and function of circular RNA KIF4A in colorectal cancer and its action mechanism

WU Minghao , XIA Luzhou , ZHANG Yu

2023, 32(4):538-547. DOI: 10.7659/j.issn.1005-6947.2023.04.008

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Background and Aims The circular RNA KIF4A (circKIF4A) has been found to play an important role in the malignant progression of various tumors. However, the biological role of circKIF4A in colorectal cancer has not been reported yet. Therefore, this study was conducted to investigate the effects and mechanisms of circKIF4A on the biological behavior of colorectal cancer.Methods The expressions of circKIF4A in different colorectal cancer cell lines and colonic mucosal epithelial cells as well as in colorectal cancer tissues and adjacent normal tissues were detected using qRT-PCR. After knocking down the expression of circKIF4A in colorectal cancer SW620 cells using siRNA, the cell growth, colony formation, invasion ability, as well as changes in the intracellular ratio of total glutathione (T-GSH) to oxidized glutathione (GSSG) and the expression of ferroptosis inhibitor protein SLC7A11 were detected. The target microRNAs (miRNAs) of circKIF4A and downstream target genes were predicted and analyzed using bioinformatics software and dual-luciferase reporter gene assay, and validation experiments were also perfromed.Results Compared to normal colonic epithelial cells and adjacent tissue, the expressions of circKIF4A were significantly upregulated in different colorectal cancer cell lines and cancer tissue (all P<0.05). Knockdown of circKIF4A resulted in significantly decreased cell growth, colony formation, invasion ability, intracellular T-GSH/GSSG ratio, and SLC7A11 protein expression in SW620 cells (all P<0.05). Prediction and analysis revealed the presence of a miR-515-5p binding site on the circKIF4A sequence, and SLC7A11 was identified as a downstream target gene of miR-515-5p. Validation results showed that miR-515-5p overexpression with simultaneous circKIF4A suppression had the most the inhibitory effect on SLC7A11 protein expression in SW620 cells among different treatments (P<0.05).Conclusion The expression of circKIF4A is upregulated in colorectal cancer cells and promotes the growth and invasion of colorectal cancer cells. Its mechanism may be associated with ferroptosis mediated by the circKIF4A-miR-515-5p-SLC7A11 axis.

9 Comparative study of inflammatory reaction, adhesion and mesh shrinkage following diaphragmatic fixation with different types of meshes in rats

MAIMAITI· Yisireyili , ALIMUJIANG· Maisiyiti , AIKEBAIER· Aili , LI Yiliang , WANG Yongkang , ABABOKELI· Wusiman , KELIMU· Abudureyimu

2023, 32(4):548-556. DOI: 10.7659/j.issn.1005-6947.2023.04.009

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Background and Aims Esophageal hiatal hernia is a common surgical condition, which is usually treated by tension-free mesh repair in clinical practice. However, there is still a relative lack of experimental data on the selection and application effectiveness of different types of meshes in esophageal hiatal hernia repair. Therefore, this study was conducted to compare the effects of fixing polypropylene mesh and composite mesh on the surrounding tissues and their own shrinkage at the diaphragmatic defect in rats, in order to provide reference for the selection of esophageal hiatal hernia meshes in clinical practice.Methods Male Sprague-Dawley rats underwent exposure of the gastroesophageal hiatus by separating the gastroesophageal junction from the liver. A lightweight polypropylene mesh (polypropylene mesh group) or a composite mesh (composite mesh group) was respectively fixed to the diaphragmatic tissue at the hiatal hernia site using monofilament sutures, or no mesh fixation was performed (sham surgery group). Body weight and food intake of each rat in each group were recorded at postoperative day 7, 15, and 30. Rats were sacrificed after 30 d, and the degree of mesh shrinkage, adhesion strength, and histopathological changes in the diaphragmatic tissue were analyzed.Results There were no significant changes in body weight and daily food intake before and after surgery in all groups (all P>0.05). The extent and severity of adhesion between the diaphragmatic tissue and the mesh were significantly lower in the composite mesh group than those in the polypropylene mesh group (both P<0.05). Both mesh types showed mesh shrinkage, but the postoperative mesh area was significantly larger and the shrinkage rate was significantly lower in the composite mesh group than those in the polypropylene mesh group (both P<0.05). Compared to the sham surgery group, local muscle fiber atrophy, as well as infiltration of inflammatory cells such as lymphocytes and macrophages, were observed in the diaphragmatic tissue of both the polypropylene mesh group and the composite mesh group. The fibrous encapsulation layer of the diaphragmatic tissue in the composite mesh group appeared thicker, but the adhesion was thinner, easily separated from the intra-abdominal organs. Compared to the sham surgery group, the expression of surface markers for macrophages (CD68) and T lymphocytes (CD3) in the diaphragmatic tissue was significantly increased in both the polypropylene mesh group and the composite mesh group, but the proportion of positive cells expressing CD68 and CD3 was significantly lower in the composite mesh group compared to the polypropylene mesh group (both P<0.05).Conclusion The composite mesh is superior to polypropylene mesh in terms of adhesion, inflammatory response, and mesh shrinkage, and it has good biocompatibility and stability, therefore, it is recommended for clinical use.

10 Identification of prognostic microRNAs in colorectal adenocarcinoma and prognostic prediction model construction based on bioinformatics analysis

XIANG Yao , WANG Junpu , ZHOU Weihong , REN Jianqiang , XING Wenwen , CHEN Dongliang , HUANG Meiyuan

2023, 32(4):557-565. DOI: 10.7659/j.issn.1005-6947.2023.04.010

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Background and Aims Colorectal adenocarcinoma (COAD) is one of the major causes of cancer-related mortality, and accurate prediction of prognosis and assessment of survival risk factors in COAD patients are particularly important. MicroRNAs (miRNAs) extensively participate in regulating tumor biology by targeting downstream mRNA and have become promising biomarkers for application research. This study aims to identify prognostic miRNAs for COAD through bioinformatics methods and to construct a prognostic prediction model, providing references for COAD prognosis determination and individualized treatment planning.Methods Clinical information and miRNA-seq data of COAD patients were downloaded from the TCGA database to obtain differentially expressed miRNAs. Key prognostic miRNAs were obtained through univariate and multivariate Cox proportional hazard regression models, and a risk score calculation formula was constructed using the multivariate Cox regression model. The Kaplan-Meier method was used to analyze the survival status of high- and low-risk patients, and the sensitivity and specificity of the risk score were evaluated using ROC curves. Internal validation was performed by randomly selecting 50% of cases from the sample. The prognostic risk nomogram model was used to determine the clinical and pathological parameters and risk scores of COAD patients using a column diagram model. The Targetscan and miRDB databases were used to predict target genes of the prognostic miRNA model, and the String database was used to analyze protein-protein interactions.Results Differential expression analysis identified 320 miRNAs, among which 167 were upregulated and 153 were downregulated. Univariate and multivariate Cox proportional hazards regression analysis of the differentially expressed miRNAs revealed miR-503-5p, miR-335-3p, miR-185-5p, miR-4436b-5p, and miR-125b-2-3p as key prognostic miRNAs for COAD patients. The survival analysis results, combined with risk score, showed that patients with high-risk scores had significantly worse prognosis than those with low-risk scores (P=0.005 6), which was also validated in a randomly selected internal validation group (P=0.014). The area under the ROC curve of the 1-, 3-, and 5-year risk scoring models were 0.666, 0.724, and 0.707, respectively, while the values for the internal validation group were 0.681, 0.699, and 0.703, respectively. Cox regression analysis showed that the consistency coefficient for the predictive nomogram of COAD was 0.836. Univariate and multivariate Cox analysis showed that the risk score was an independent prognostic factor for COAD in the modeling group and the internal validation group (both P<0.01). The miRNA target gene prediction revealed 87 target genes, while the protein-protein interaction network analysis identified 10 key genes involved in protein interactions.Conclusion The COAD prognostic miRNA model and the nomogram constructed based on factors such as age, AJCC stage, T stage, radiotherapy and chemotherapy, and risk score can accurately predict the risk of COAD, providing a theoretical basis for identifying high or low-risk patients, accurately predicting prognosis, and assessing patient survival risk.

11 Application of artificial intelligence-assisted technology in assessment of HER-2 expression in different regions of primary lesions of advanced gastric cancer and prognostic estimation

LIU Yang , GUO Ziyang , LIU Yueping , WANG Xinran , WANG Zihan , YANG Jiaxuan , DING Pingan , ZHENG Tao , TIAN Yuan , GUO Honghai , TAN Bibo , FAN Liqiao , LI Yong , ZHAO Qun

2023, 32(4):566-574. DOI: 10.7659/j.issn.1005-6947.2023.04.011

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Background and Aims The expression of human epidermal growth factor receptor 2 (HER-2) in gastric cancer exhibits significant heterogeneity, and comprehensive evaluation of HER-2 status in patients is advantageous for identifying potential beneficiaries of anti-HER-2 therapy. Artificial intelligence (AI)-assisted microscopy can integrate judgments on HER-2 status through extensive slide readings and reduce visual errors in human assessments. This study was performed to evaluate the practicality and feasibility of AI in evaluating HER-2 status in multiple regions of primary gastric cancer lesions.Methods A total of 264 postoperative specimens from patients with advanced gastric cancer were evaluated for HER-2 expression in the same region using two methods: visual assessment with a conventional light microscope and AI-assisted microscopy. The accuracy of AI in HER-2 evaluation in gastric cancer was evaluated. Additionally, using AI-assisted microscopy, HER-2 expression in other regions of the primary lesion in the gastric cancer patients was assessed. The higher HER-2 score between the two regions was used as the final interpretation result. Furthermore, the associations of HER-2 overexpression with clinicopathological features and postoperative survival of advanced gastric cancer patients were analyzed.Results There was no statistically significant overall difference in HER-2 scores among visual assessment, AI-assisted microscopy, and the gold standard (P>0.05), but AI-assisted microscopy showed higher consistency compared to visual assessment with the gold standard (κ=0.86 vs. κ=0.81, P<0.05). The results of HER-2 evaluation in two different regions of the primary lesion in gastric cancer using AI showed inconsistency in 55 cases, with a discordance rate of 20.8%. The HER-2 overexpression rate was 29.9% in region 1 and 31.0% in region 2. The comprehensive evaluation of HER-2 overexpression rate, taking the higher score between the two regions, was 35.2%. The HER-2 overexpression rate based on comprehensive evaluation of HER-2 expression in the two regions was higher than that of single-region assessment, but the difference was not statistically significant (P>0.05). Further analysis revealed that HER-2 heterogeneity in primary gastric cancer lesions was significantly associated with tumor differentiation and Lauren classification (both P<0.05). Survival analysis showed that the median 3-year overall survival was 23 months with a 3-year survival rate of 33.4% in HER-2 overexpressing advanced gastric cancer patients, while it was 29 months with a 3-year survival rate of 44.6% in HER-2 non-overexpressing advanced gastric cancer patients, and the difference was statistically significant (P<0.05).Conclusion AI is a practical and reliable tool for evaluating HER-2 expression in different regions of primary gastric cancer, enabling a more comprehensive and accurate assessment of HER-2 status in gastric cancer and improving the detection rate of HER-2 overexpression. HER-2 heterogeneous expression is more likely to occur in gastric cancer patients with moderate to low differentiation and non-intestinal type Lauren classification, and HER-2 overexpression may be a poor prognostic factor in resectable advanced gastric cancer patients.

12 Application of pre-expansion of posterior gastric space in laparoscopic radical proximal gastrectomy

LI Lei , MA Jiachi , ZHANG Chensong , CHEN Yuzhong , DU Jun , WANG Qingkang , FU Wei

2023, 32(4):575-582. DOI: 10.7659/j.issn.1005-6947.2023.04.012

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Background and Aims In radical gastrectomy for proximal gastric cancer, bleeding and spleen damage are likely to occur when dealing with short gastric vessels, especially in some obese patients with short spleen-gastric ligaments at the upper pole of the spleen. The author's team has previously used a surgical method of pre-expanding the posterior gastric space, which effectively solves this problem. This study was performed to compare the clinical efficacy of laparoscopic proximal gastrectomy with pre-expansion of the retrogastric space versus conventional laparoscopic proximal gastrectomy, and explore the value of the pre-expansion method in laparoscopic proximal gastrectomy for gastric cancer.Methods The clinical data of 196 patients who underwent laparoscopic proximal radical gastrectomy in the Department of Oncology of the First Affiliated Hospital of Bengbu Medical College from January 2019 to December 2021 were retrospectively analyzed. Of the patients, 99 cases underwent radical proximal gastrectomy with pre-expansion of the retrogastric space (study group), 97 cases received conventional proximal gastrectomy (control group). The clinical variables were compared between the two groups of patients.Results There were no significant differences in general information such as age, sex, BMI, tumor location, tumor stage, surgical method, and esophagojejunostomy method between the two groups (all P>0.05). All patients in both groups completed the laparoscopic surgery uneventfully, with the same range of lymph node dissection and without conversion to open surgery. Compared with the control group, the study group had a significantly shorter average operative time [(100.3±25.8) min vs. (130.7±43.2) min, P=0.000] and significantly less average intraoperative blood loss [(35.0±5.7) mL vs. (44.9±4.7) mL, P=0.000]. Splenic injury occurred in 5 cases (5.2%) in the control group during the surgery, while no intraoperative spleen injury occurred in the study group, but the difference was not statistically significant (P>0.05). There were no statistically significant differences between the two groups in terms of the number of lymph node dissection, postoperative drainage volume, drainage time, postoperative hospital stay, hospital costs, and incidence of surgical complications (all P>0.05). No serious postoperative complications occurred in both groups of patients.Conclusion The surgical method of pre-expanding the posterior gastric space in laparoscopic proximal gastrectomy has the advantages of less intraoperative bleeding, shorter operation time, and reduced iatrogenic splenic injury. So, it is recommended for clinical use.

13 Bibliometric analysis of global trends in research of short bowel syndrome over the past 30 years

TENG Yuanyuan , HUANG Biling , PENG Shuqin , LI Mingliu , TAN Min , ZHANG Yi , NIU Guankai , WANG Min

2023, 32(4):583-593. DOI: 10.7659/j.issn.1005-6947.2023.04.013

[Abstract](440) [HTML](501) [PDF 2.27 M](1272)

Abstract:
Background and Aims Short bowel syndrome is a rare disease caused by extensive small bowel resection, which has gradually attracted the attention of scholars in recent years. However, there is currently no related bibliometric study on this disease. Therefore, this study was conducted to describe the hotspots and trends in short bowel syndrome research over the past 30 years through bibliometric analysis.Methods Publications related to short bowel syndrome between 1991 and 2021 were searched in the Web of Science core database and imported into VOSviewer and CiteSpace software in plain text format. The data were processed using bibliometric methods to perform literature visualization analysis of authors, countries, institutions, highly cited literature, co-citation analysis, keywords, and references.Results A total of 3 439 articles were retrieved, involving 12 457 authors, 2 557 organizations, 74 countries/regions, and 779 journals. The literature cited a total of 64 834 articles authored by 43 194 individuals from 8 713 journals. Among them, the United States made the most significant contribution, and Wales PW was the most productive author. The University of Toronto was the most prolific institution, and the Journal of Pediatric Surgery was the core journal in this field. Keyword analysis showed that Short Bowel Syndrome, Intestinal Failure, Children, and Parenteral Nutrition were high-frequency keywords. Currently, research focuses on the classification, treatment, and management of this disease.Conclusion Over the past 30 years, the number of publications on short bowel syndrome has gradually increased, and the United States is at the forefront of research in this field. In addition, the classification, treatment, and management of short bowel syndrome have become potential hotspots.

14 Progress of application of neoadjuvant chemotherapy in resectable colon cancer

WU Xiaofeng , XU Yunhua , FU Guang , HUANG Qiulin , XIAO Shuai

2023, 32(4):594-603. DOI: 10.7659/j.issn.1005-6947.2023.04.014

[Abstract](358) [HTML](1146) [PDF 782.06 K](1220)

Abstract:
Neoadjuvant chemotherapy (NACT) refers to a comprehensive treatment plan for patients with potentially resectable tumors by performing systemic chemotherapy before tumor resection or radiotherapy, and then continuing to complete the whole course of chemotherapy after surgery or radiotherapy, with the aim of eliminating micrometastases, tumor downstaging and reducing surgical difficulty. Colon cancer is one of the most common cancers, and radical tumor resection combined with postoperative adjuvant chemotherapy is the main treatment for potentially curable colon cancer. Although this treatment mode has significantly improved the prognosis of patients, postoperative local recurrence and distant metastasis are still the main causes of death. In recent years, NACT has been introduced as a treatment option for potentially curable colon cancer patients such as those with locally advanced colon cancer or with liver metastases and resectable primary tumor. However, there is still a significant controversy regarding whether colon cancer patients are suitable for NACT and the choice of NACT regimens. Here, the authors address the progress and controversies of NACT in locally advanced colon cancer and resectable colon cancer liver metastasis, as well as the role of imaging examinations in NACT.

15 Advances in the anatomy study of the mesenteric artery

ZHAO Botian , DING Yuanyi , NIU Wenbo , HU Xuhua , YU Bin

2023, 32(4):604-614. DOI: 10.7659/j.issn.1005-6947.2023.04.015

[Abstract](651) [HTML](583) [PDF 1.04 M](1367)

Abstract:
In recent years, the incidence of colorectal cancer has been continuously increasing, and laparoscopic radical surgery for colorectal cancer is being increasingly applied in clinical practice. In laparoscopic radical surgery for left-sided colon and rectal cancer, the inferior mesenteric artery (IMA) is one of the most important anatomical landmarks, and its handling is also an important step in the surgical process, which can affect the surgical quality, postoperative recovery, and patient prognosis. Inappropriate handling of the IMA during surgery can cause vascular injury, bleeding that can contaminate the surgical field, prolong the operative time, and improper ligation of blood vessels can lead to colon ischemia at the surgical site, thereby increasing the risk of complications such as anastomotic leakage. Therefore, accurate understanding of vascular anatomy is the basis of successful tumor radical surgery in left-sided colon and rectal tumor surgery. The anatomy of the IMA varies greatly, and different results are obtained through various methods such as anatomy, angiography, or surgical research, and there are differences in anatomy due to different races and even regions. It is necessary to summarize and classify them. Although the origin of the IMA varies slightly, there are significant differences in types of branches, number of branches, and the presence or absence of certain branches among different individuals. The results of different researchers are also not exactly the same. Although there is no unified classification system for the anatomical classification of the IMA, the similarities include three major types of branches, including the left colo-sigmoid trunk, the recto-sigmoid trunk or common trifurcation. From the perspective of surgical treatment of colorectal cancer, it is of great significance to analyze the anatomical structure data of the IMA and its branches recorded during preoperative imaging examination and surgery. Therefore, this article summarizes the reported anatomical types and relative relationships between different branches in the literature, describes the normal and variant anatomical structure of the IMA, including a brief overview of relevant embryology, and introduces a new classification system to evaluate and summarize the anatomical structure of the IMA, so as to provide theoretical reference and guidance for surgeons to evaluate the mesenteric vascular system before and during surgery, improve overall surgical quality, achieve sufficient and reasonable tumor radical resection, and optimize surgical treatment.

16 Research progress on the interaction between PD-1/PD-L1 and tumor-associated macrophages in carcinogenesis

XIAO Guohui , CHEN Lang , YU Wuhan , LI Tengfei , ZHANG Youcheng

2023, 32(4):615-621. DOI: 10.7659/j.issn.1005-6947.2023.04.016

[Abstract](305) [HTML](874) [PDF 679.02 K](1286)

Abstract:
Programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis and tumor-associated macrophages (TAMs) in the tumor microenvironment are closely related to carcinogenesis. TAMs are mainly categorized as the anti-tumoral M1 phenotype and the pro-tumoral M2 phenotype, with M2-TAMs being the main type of infiltrating macrophages in tumor tissue. Recent research has mainly focused on the inhibition of the anti-tumor effect of TAMs by the PD-1/PD-L1 axis, and the involvement of the cytokines, chemokines, and exosomes that are secreted by TAMs in regulating the expression of PD-1/PD-L1. Here, the authors review the role of PD-1/PD-L1 and TAMs in tumorigenesis, summarize the possible interactions between the them, and discuss the impact of targeted regulation of TAMs on the effectiveness of PD-1/PD-L1 monoclonal antibody therapy for tumors.

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Volume 32,Issue 4,2023 Table of Contents

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