Application progress of artificial intelligence in the diagnosis of esophageal cancer / 中国胸心血管外科临床杂志

@#Esophageal cancer is an aggressive malignancy with high morbidity and poor prognosis. Symptoms of early esophageal cancer are insidious and difficult to detect, while advanced esophageal obstruction, lesion infiltration and metastasis seriously affect patients’ quality of life. Early detection and treatment can help to increase the survival chance of patients. Recently, artificial intelligence (AI) has shown remarkable success in diagnosis of esophageal cancer, highlighting the great potential of new AI-assisted diagnostic modalities. This paper aims to review recent progress of AI in the diagnosis of esophageal cancer and to prospect its clinical application.

Interpretation of the updates of the NCCN esophageal and esophagogastric junction cancers clinical practice guidelines in oncology (version 3. 2023) / 中国胸心血管外科临床杂志

@#Esophageal cancer is the seventh most common cancer worldwide. On August 29, 2023, National Comprehensive Cancer Network (NCCN) released the NCCN esophageal and esophagogastric junction cancers clinical practice guidelines in oncology (version 3. 2023). This article aims to highlight the key updates in treatment and follow-up recommendations between the version 3 and the version 2 in 2023, providing the latest guidance for the management of esophageal cancer in our country.

Chinese Medicine Regulates Signaling Pathways Related to Esophageal Cancer： A Review / 中国实验方剂学杂志

Esophageal cancer is a common malignant tumor of the digestive tract. At present， the pathogenesis of esophageal cancer has not been fully clarified. Although surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy have achieved good clinical results in the treatment of esophageal cancer， there are still many complications and severe adverse reactions. As an important part of traditional Chinese medicine （TCM）， in recent years， many basic experiments and clinical studies have proved that Chinese medicine has a good effect in treating esophageal cancer. At the same time， the multi-component and multi-target characteristics of Chinese medicine and unclear pathogenesis of esophageal cancer determine that there are some problems such as unclear mechanisms of Chinese medicine in preventing and treating esophageal cancer. It is necessary to start with modern medicine and reveal the mechanism of Chinese medicine in preventing and treating diseases from the aspects of molecular biology and network pharmacology. It is believed in TCM that the occurrence of esophageal cancer is mostly attributed to stagnation of liver Qi， phlegm stasis and Qi stagnation， fluid consumption and heat accumulation， the decline of healthy Qi， and the cementation of cancer toxicity. According to the literature review， Chinese medicinal compounds mainly include tonic formulae （such as Liu Junzitang）， drying and moistening formulas （such as Qigesan）， and heat-clearing formulas （such as Fufang Kushen injection）. Chinese medicinal monomers mainly include drugs potent in attacking poison and killing insects， clearing heat， activating blood and resolving stasis， and regulating Qi， which is consistent with the etiology and pathogenesis of esophageal cancer in TCM. It is also found that Chinese medicine can promote cell apoptosis and autophagy， block cell cycle， and reverse cell resistance by regulating phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， neurogenic locus notch homolog protein （Notch）， Wnt/β-catenin， mitogen-activated protein kinase （MAPK）， nuclear factor-κB （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and other related signaling pathways， but there is no systematic summary. This study systematically summarized the relevant signaling pathways of Chinese medicine in regulating esophageal cancer， which is helpful to clarify the relevant mechanisms of Chinese medicine in the process of esophageal cancer occurrence， development， invasion， and metastasis， so as to provide new targets and new perspectives for the treatment of esophageal cancer and promote the modernization of TCM.

Role of NF-κB Signaling Pathway in "Reflux Esophagitis-esophageal Cancer" and Traditional Chinese Medicine Intervention：A Review / 中国实验方剂学杂志

Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise， and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa， causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue， which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B （NF-κB） signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation， autophagy， apoptosis， and inflammatory response of esophageal epithelial cells and tumor cells， accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently， there is no specific treatment for reflux esophagitis and esophageal cancer， and large side effects often appear. Therefore， finding a promising and safe drug remains a top priority. In recent years， traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway， and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， but there is a lack of comprehensive and systematic elaboration. Therefore， this paper summarized the relevant studies in recent years， analyzed the relationship among NF-κB signaling pathway， reflux esophagitis， esophageal cancer， and transformation from inflammation to cancer， and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer.

Self-expanding Metal Stents in Malignant Obstruction of the Esophagus: A 25-Year Multicentric Study

Background: Self-expanding metal prostheses improve dysphagia in patients with incurable esophageal cancer (EC). New stents have been introduced, and chemoradiotherapy has been implemented for EC, changing patients' risk profiles. It is unknown whether this has affected palliation with stents. Patients and methods: Retrospective study in three centers in Medellín-Colombia; patients undergoing placement of palliative esophageal prostheses for malignant dysphagia (1997-2022). Major and minor complications after implantation, the influence of oncological therapies, and survival were evaluated for 1997-2009 (n = 289) and 2010-2022 (n = 318). Results: 607 patients underwent esophageal prostheses; 296 (48.8%) became complicated. It was higher in the second period (52.5% vs. 48.1%), as were major complications (20.8% vs. 14.2%, p = 0.033), with no differences in minor complications (33.9% vs 31.8%, p = 0.765). Also, 190 (31.3%) patients presented with recurrent dysphagia, stable in both periods. Migration increased over time (from 13.1% to 18.2%, p = 0.09). The most common minor adverse event was pain, increasing over time (from 24.9% to 33.95%, p < 0.01), and associated factors were chemoradiotherapy, absence of fistula, and squamous cell carcinoma. Acid reflux decreased in the second group (p = 0.038). Twelve percent of patients required another intervention for feeding. Survival was not impacted by time and use of stents. Conclusions: Stents are an alternative in non-surgical malignant dysphagia, although recurrent dysphagia has not decreased over time. Minor stent-related complications are increasing in association with the implementation of chemoradiotherapy.

Antecedentes: Las prótesis metálicas autoexpandibles mejoran la disfagia en pacientes con cáncer esofágico (CE) incurable. En las últimas décadas se han introducido nuevos tipos de stents y se ha implementado la quimiorradioterapia para el CE, generando cambios en los perfiles de riesgo de los pacientes. Se desconoce si estos cambios han afectado la paliación con stents. Pacientes y métodos: Estudio retrospectivo en tres centros de Medellín-Colombia; pacientes sometidos a colocación de prótesis esofágicas paliativas para disfagia maligna (1997-2022). Se evaluaron en dos períodos: 1997-2009 (n = 289) y 2010-2022 (n = 318), complicaciones mayores y menores después del implante, la influencia de las terapias oncológicas y la sobrevida. Resultados: Se evaluaron 607 pacientes sometidos a prótesis esofágicas. 296 (48,8%) se complicaron, y fue mayor en el segundo periodo (52,5% frente a 48,1%), al igual que las complicaciones mayores (20,8% frente a 14,2%, p = 0,033), sin diferencias en complicaciones menores (33,9% frente a 31,8%, p = 0,765). 190 (31,3%) pacientes presentaron disfagia recurrente, estable en ambos períodos. La migración aumentó con el tiempo (de 13,1% a 18,2%, p = 0,09). El evento adverso menor más frecuente fue dolor, que aumentó con el tiempo (de 24,9% a 33,95%, p < 0,01), y los factores asociados fueron quimiorradioterapia, ausencia de fístula y carcinoma de células escamosas. El reflujo ácido disminuyó en el segundo grupo (p = 0,038). El 12% de pacientes requirieron otra intervención para alimentarse. No se impactó la sobrevida con el tiempo y uso de stents. Conclusiones: Los stents son una alternativa en la disfagia maligna no quirúrgica, aunque la disfagia recurrente no ha disminuido con el tiempo. Las complicaciones menores relacionadas con el stent van en aumento, asociadas a la implementación de la quimiorradioterapia.

Morbilidad y mortalidad de pacientes operados de cáncer de esófago / Morbidity and Mortality of Patients Operated on for Esophageal Cancer

Introducción: El tratamiento principal del cáncer esofágico es la esofagectomía. Objetivo: Determinar la morbilidad y mortalidad de los pacientes operados de cáncer esofágico. Métodos: Se realizó un estudio observacional, descriptivo y transversal en 87 pacientes operados de cáncer esofágico en el Servicio de Cirugía General del Hospital Provincial Docente Saturnino Lora de Santiago de Cuba durante el período comprendido de 2014 a 2018. Resultados: Dos pacientes en estadio II (100,0 por ciento) recibieron tratamiento quirúrgico curativo y 12 en estadio III (17,9 por ciento). Recibieron tratamiento quirúrgico paliativo 55 (82,1 por ciento) enfermos en estadio III y 18 (100,0 por ciento) en estadio IV. Predominó la técnica transhiatal de Denk-Sloan-Orringer aplicada en 10 (71,4 por ciento) pacientes. La gastrostomía predominó como proceder paliativo para alimentación en 53 (76,2 por ciento) pacientes. Se reportaron 45 complicaciones; el 53,3 por ciento de tipo médica, en las que prevalecieron las respiratorias: bronconeumonía (13,3 por ciento) y distrés respiratorio (11,1 por ciento). En cambio, el 46,7 por ciento de las complicaciones fueron de tipo quirúrgicas: infección del sitio operatorio (20,0 por ciento), seguida de la fuga anastomótica (15,6 por ciento). Fallecieron 16 (18,4 por ciento) pacientes del total de la serie. Las causas de muerte predominantes fueron el distrés respiratorio (31,3 por ciento) y la disfunción múltiple de órganos (25,0 por ciento). Conclusiones: La esofagectomía abierta o mínimamente invasiva se erige como el tratamiento quirúrgico de elección para el tratamiento del cáncer esofágico con intención curativa, proceder con elevada morbilidad y mortalidad a escala mundial. Los resultados de esta investigación coinciden con los reportados en la literatura médica nacional y extranjera(AU)

Introduction: The main treatment for esophageal cancer is esophagectomy. Objective: To determine the morbidity and mortality of patients operated on for esophageal cancer. Methods: An observational, descriptive and cross-sectional study was carried out with 87 patients operated on for esophageal cancer in the general surgery service of Hospital Provincial Docente Saturnino Lora, of Santiago de Cuba, during the period from 2014 to 2018. Results: Curative surgical treatment was received by 2 patients (100.0 percent) in stage II and 12 patients (17.9 percent) in stage III. Palliative surgical treatment was received by 55 ill patients (82.1 percent) in stage III and 18 ill patients (100.0 percent) in stage IV. There was a predominance of the Denk-Sloan-Orringer transhiatal technique, applied in 10 (71.4 percent) patients. Gastrostomy predominated in 53 (76.2 percent) patients as a palliative procedure for feeding. Forty-five complications were reported, 53.3 percent of which were medical, with respiratory complications prevailing: bronchopneumonia (13.3 percent) and respiratory distress (11.1 percent). On the other hand, 46.7 percent of the complications were surgical: surgical site infection (20.0 percent), followed by anastomotic leak (15.6 percent). Out of the total series, 16 (18.4 percent) patients died. The predominant causes of death were respiratory distress (31.3 percent) and multiple organ dysfunction (25.0 percent). Conclusions: Open or minimally invasive esophagectomy stands out as the surgical treatment of choice for esophageal cancer with curative purposes, being a procedure with high morbidity and mortality worldwide. The results of this research coincide with those reported in the national and foreign medical literature(AU)

Macroscopic Clinical Medication Pattern of Traditional Chinese Medicine for Esophageal Cancer in Recent Ten Years Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo explore the macroscopic medication pattern of traditional Chinese medicine （TCM） in treating esophageal cancer （EC） and provide medication references for the clinical application of TCM in EC treatment. MethodRelevant literature on TCM treatment of EC was retrieved from three major Chinese databases： China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP. Information about Chinese herbal medicines was entered into Excel to establish a prescription database for EC. The data were standardized， summarized， and subjected to frequency analysis， association rules， and cluster analysis of medication in the prescriptions. Based on the TCM classification of EC syndromes， clinical indications corresponding to each syndrome were identified， and high-frequency drugs and drug pairs were analyzed correspondingly with syndromes. ResultA total of 136 prescriptions containing 240 Chinese herbal medicines were screened， with a cumulative frequency of 1 853 times. The top 5 frequently used Chinese herbal medicines were Glycyrrhizae Radix et Rhizoma， Poria， Atractylodis Macrocephalae Rhizoma， Astragali Radix， and Pinelliae Rhizoma. In terms of functions， the Chinese herbal medicines were mainly deficiency-tonifying， urination-promoting and dampness-draining， deficiency-tonifying， deficiency-tonifying， and phlegm-resolving and cough and dyspnea-relieving ones. The statistical analysis of flavor， property， and meridian tropism showed that Chinese herbal medicines were mainly bitter and sweet， warm， cold， and neutral， and acted on the spleen， lung， and stomach meridians. Association rule analysis yielded nine potential drug combinations， and cluster analysis of high-frequency drugs resulted in four combination categories. The four TCM syndromes for EC corresponded to respective clinical indications， treatment drugs， and drug pairs. ConclusionTonifying deficiency， reinforcing healthy Qi， descending adverse Qi， resolving phlegm， activating blood， and resolving stasis are the basic principles of TCM treatment for EC， which are supplemented by clearing heat and dissipating mass while focusing on regulating and smoothing the qi movement. The drug combinations obtained from high-frequency drug and association rule analysis provide references for different TCM syndrome treatments of EC， offering valuable insights for clinical medication.

Correlation Between Peripheral Blood Biomarkers and Immune Checkpoint Inhibitors in Treatment of Advanced Esophageal Cancer / 肿瘤防治研究

Objective To explore the effect of peripheral blood markers on the efficacy and prognosis of patients with advanced esophageal cancer treated with immune checkpoint inhibitors (ICIs). Methods The case data of 61 patients with advanced esophageal cancer who met the inclusion criteria were collected. Data on clinical indicators and peripheral blood markers as well as objective response rate (ORR) and progression-free-survival (PFS) were obtained. Results The median PFS of the included patients was 7.10 months (95%CI: 5.12-9.07). The ORR of patients with baseline lactate dehydrogenase (LDH) < 201 was better than that of patients with LDH≥201 (P < 0.05). Univariate analysis showed that baseline LDH0 < 201, neutrophil to lymphocyte ratio (NLR) < 3.9, platelet-to-lymphocyte ratio (PLR) < 240.3, and LDH1 < 249.0 two weeks after ICI treatment were significantly associated with significant improvement in PFS (P < 0.05). In multivariate analysis, patients with NLR0 < 3.9 had longer PFS (P < 0.05). Conclusion LDH0 < 201, NLR0 < 3.9, PLR0 < 240.3, and LDH1 < 249.0 are positively correlated with the prognosis of patients with advanced esophageal cancer treated with ICIs.

Effects of X-ray volume imaging registration methods on position verification for radiotherapy in treatment of middle/lower-segment esophageal cancer / 中国辐射卫生

@#<b>Objective</b> To compare the set up errors derived from different registration methods of the X-ray volume imaging (XVI) system for radiotherapy in the treatment of middle/lower-segment esophageal cancer, and to provide a reference for radiation treatment of esophageal cancer. <b>Methods</b> We randomly selected 63 patients with middle/lower-segment esophageal cancer, and obtained their reconstructed XVI images at the first therapy to perform automatic registration with gray-value and bone registration methods. We acquired and compared the three translation errors (along <i>x</i> [left to right], <i>y</i> [head to feet], and <i>z</i> [front to back] axes) and three rotation errors (around the <i>x</i>, <i>y</i>, and <i>z</i> axes) derived from the two registration methods. <b>Results</b> Gray-value registration had significantly smaller translation errors along the <i>x</i> and <i>z</i> axes than bone registration (<i>x</i> azes <i>t</i> = −2.78, <i>z</i> azes <i>t</i> = −2.15, <i>P</i> < 0.05), but there was no significant difference along the <i>y</i> axes (<i>P</i> > 0.05). The rotation errors around the three axes were all smaller than 1°, and were smaller with gray-value registration than with bone registration, but without significant differences (<i>P</i> > 0.05). <b>Conclusion</b> We recommend gray-value registration for radiotherapy in the treatment of middle/lower-segment esophageal cancer. Manual verification or fine-tuning is recommended after automatic registration in clinical practice. Besides translation errors, rotation errors should also be paid attention to.

Ethyl Acetate Extract of Qigesan Intervenes in Migration and Invasion of Esophageal Cancer Cells via Inhibiting TGF-β1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Qigesan （QGS） in intervening in the migration and invasion of esophageal carcinoma TE-1 cells. MethodMicroarray technology was used to screen differentially expressed genes （DEGs） in the normal group and the QGS group， and the ontological functions and signaling pathways of DEGs were analyzed. The thiazolyl tetrazolium （MTT） assay was used to detect the effect of QGS on the viability of TE-1 cells. In the subsequent experiments for verification， a blank group， a transforming growth factor-β1 （TGF-β1） group， a TGF-β1 + QGS group， and a TGF-β1 + SB431542 group were set up. The cell morphology in each experimental group was observed by microscopy. The migration and invasion abilities of cells were detected by wound healing assay， and the mRNA expression levels of E-Cadherin， vimentin， Smad2， and Smad7 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of E-Cadherin， vimentin， p-Smad2/3， Smad2/3， and Smad7 was detected by Western blot. ResultThere were 1 487 DEGs between the QGS group and the blank group， including 1 080 down-regulated ones （accounting for 72.63%） and 407 up-regulated ones. The down-regulated genes were mainly involved in biological processes such as cytoskeletal protein binding， ATP binding， adenylate nucleotide binding， and adenylate ribonucleotide binding， and the involved Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways included TGF-β signaling pathway， cell cycle， extracellular matrix-receptor interaction protein， tumor pathways， and oocyte meiosis. The up-regulated genes were mainly involved in RNA binding， DNA binding， transcriptional regulator activity， transcriptional activator activity， and nucleotide binding， and the KEGG pathways involved mainly included mitogen-activated protein kinase （MAPK） signaling pathway， bladder cancer， renal cell carcinoma， cancer pathways， and p53 signaling pathway. Compared with the blank group， the inhibition rate of cell viability of TE-1 cells increased after QGS （20， 30， 40， 60， 80 mg·L-1） intervention for 12， 24， 36， 48， 60 h （P<0.05）， and the inhibition rate was time- and dose-dependent. Compared with the blank group， the TGF-β1 group showed lengthened cells with fibroblast phenotype. Compared with the TGF-β1 group， the TGF-β1 + QGS group showed shortened cells with normal morphology and epithelial phenotype. The cell morphology in the TGF-β1 + SB431542 group was similar to that of the TGF-β1 + QGS group. Compared with the blank group， the TGF-β1 group showed potentiated ability of cell migration and invasion （P<0.05）. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1 + SB431542 group showed inhibited and weakened migration and invasion abilities of cells （P<0.05）. However， there was no significant difference in migration and invasion abilities between the TGF-β1 + QGS group and the TGF-β1 + SB431542 group. The mRNA expression levels of vimentin and Smad2 in the TGF-β1 group were higher （P<0.05）， and the mRNA expression levels of E-Cadherin and Smad7 were lower （P<0.05） than those in the blank group. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1+ SB431542 group exhibited decreased expression levels of vimentin and Smad2 mRNA （P<0.05）， and elevated expression levels of E-Cadherin and Smad7 mRNA （P<0.05）. Compared with the blank group， the TGF-β1 group showed up-regulated protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and reduced protein expression levels of E-Cadherin and Smad7 （P<0.05）. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1 + SB431542 group displayed decreased protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and increased protein expression levels of E-Cadherin and Smad7 （P<0.05）. ConclusionThe ethyl acetate extract of QGS inhibits the epithelial-mesenchymal transition （EMT） of TE-1 cells through the TGF-β1 pathway to reduce the migration and invasion of TE-1 cells.

Analysis of Significant Genes and Pathways in Esophageal Cancer Based on Gene Expression Omnibus Database / 中国医学科学杂志(英文版)

Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes, and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis, protein-protein interaction (PPI) network, and survival analysis based on the Gene Expression Omnibus (GEO) database.Methods By screening with highly expressed genes, we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites. Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis, PPI network, and survival analysis. Several software and platforms including Prism 8, R language, Cytoscape, DAVID, STRING, and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma (ESCC) tissue. Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer. Four genes including ALDH3A1, C2, SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer. Keratinization may greatly impact the pathogenesis of esophageal cancer. Genes ALDH3A1, C2, SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.

Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer / 中国结合医学杂志

OBJECTIVE@#To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.@*METHODS@#The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified.@*RESULTS@#Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target.@*CONCLUSION@#YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.

Efficacy and safety of neoadjuvant chemotherapy combined with PD-1 antibody for esophageal squamous cell carcinoma in the real world / 中华肿瘤杂志

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.

Pathologic assessment of esophageal cancer following neoadjuvant therapy / 中国胸心血管外科临床杂志

@#China is a country with a high incidence of esophageal cancer. Most patients are already in the locally advanced stage when first diagnosed. Preoperative neoadjuvant therapy followed by surgery has become the standard treatment mode for them. Closely related to prognosis, the evaluation of tumor response is essential. Response evaluation criteria in solid tumors is the gold standard to evaluate tumor response, but the lesions must meet the measurement standards. Tumor regression grading (TRG) systems are designed to classify regressive changes after neoadjuvant treatment based on histopathological results to reveal prognostic information. Concentrating on pathologic assessment of esophageal cancer following neoadjuvant therapy, this article reviews histopathological changes, commonly used TRG systems and current debate.

Effect of miR-524-5p on Epithelial-mesenchymal Transition in Esophageal Cancer Cells by Regulating HEG1 Expression / 肿瘤防治研究

Objective To investigate the mechanism and the effect of miR-524-5p regulating HEG1 expression on the proliferation and epithelial-mesenchymal transition of esophageal cancer cells. Methods The expression levels of miR-524-5p and HEG1 mRNA in esophageal cancer cells and normal esophageal epithelial cells were detected by qRT-PCR. KYSE30 cells were divided into miR-524-5p mimic group, miR-524-5p NC group, miR-524-5p mimic+pcDNA3.1 group, and miR-524-5p mimic+pcDNA3.1-HEG1 group. Non-transfected cells were set as the normal control group (group Control). CCK-8 method was applied to detect the proliferation ability of KYSE30 cells. Western blot analysis was conducted to detect the expression of proteins related to EMT, invasion, and migration and the HEG1 protein. Scratch and Transwell assays were applied to detect the migration and invasion abilities of KYSE30 cells. A dual-luciferase reporter gene was used to examine the targeting relationship between miR-524-5p and HEG1. Results miR-524-5p was lowly expressed in four esophageal cancer cell lines, namely, TE-1, KYSE30, KYSE150, and NEC (P < 0.05). KYSE30 cells with the lowest expression level were selected for subsequent experiments. HEG1 mRNA was highly expressed in four esophageal cancer cell lines (P < 0.05). The GEPIA database showed that HEG1 was highly expressed in esophageal cancer tumor tissues (P < 0.05). KYSE30 cells in the miR-524-5p mimic group had lower proliferation ability, colony formation number, mesenchymal marker protein expression, and migration and invasion abilities and upregulated epithelial marker protein E-cadherin level than cells in the miR-524-5p NC group (P < 0.05). The miR-524-5p mimic+pcDNA3.1-HEG1 group significantly reversed the inhibitory effect of overexpression of miR-524-5p on the proliferation, epithelial–mesenchymal transformation, invasion, and metastasis of KYSE30 cells (P < 0.05). The luciferase activity of cells in the miR-524-5p mimic and WT-HEG1 co-transfection groups was lower than that in the miR-524-5p NC and WT-HEG1 co-transfection groups (P < 0.05). Conclusion miR-524-5p is lowly expressed in EC cells and tissues. The overexpression of miR-524-5p can negatively regulate the expression of HEG1 in esophageal cancer cell line (KYSE30 cells) and reduce the proliferation, EMT process, and invasion and migration abilities of KYSE30 cells.

Cancer Death and Distribution Characteristics from 2013 to 2017 in Cixian, Hebei Province / 肿瘤防治研究

Objective To investigate the cancer death and distribution characteristics of residents in Cixian County. Methods In accordance with the norms of cancer registration, cancer death data from 2013 to 2017 in Cixian were collected and analyzed, and the crude cancer death rate, age-standardized mortality rates by the Chinese standard population (ASMRC), age-standardized mortality rates by the global standard population (ASMRW). Results From January 1st, 2013, to December 31st, 2017, 6 490 cases of cancer death were recorded. The average annual crude mortality rate was 202.88/100 000, ASMRC was 186.49/100 000, and the ASMRW was 189.02/100 000. The top 10 male mortality cancers were esophageal cancer, stomach cancer, trachea, bronchus and lung cancer, liver cancer, rectal cancer, cerebral nervous system cancer, colon cancer, leukemia, pancreatic cancer, and bladder cancer in order. The top 10 female mortality cancers were esophageal cancer, trachea, bronchus and lung cancer, stomach cancer, liver cancer, breast cancer, cervical cancer, colon cancer, brain, nervous system cancer, rectal cancer, and ovarian cancer. The age of death increased considerably from the age of 40 years. It increased with the increase in age and reached the peak at the age of 85 years. Conclusion Upper gastrointestinal cancer and lung cancer were the main cancers that threatened the residents of Cixian County from 2013 to 2017. Screening and comprehensive prevention of high-risk groups are still the main targets of cancer prevention and control.

Efficacy and safety of enteral nutrition with jejunostomy tube versus nasojejunal tube after radical resection of esophageal cancer: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To systematically evaluate the efficacy and safety of jejunostomy tube versus nasojejunal tube for enteral nutrition after radical resection of esophageal cancer. Methods    PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP and CBM databases were searched to collect the clinical effects of jejunostomy tube versus nasojejunal nutrition tube after radical resection of esophageal cancer from inception to October 2021. Meta-analysis was performed using RevMan 5.4 software. Results    Twenty-six articles were included, including 17 randomized controlled studies and 9 cohort studies, with a total of 35 808 patients. Meta-analysis results showed that: in the jejunostomy tube group, the postoperative exhaust time (MD=–4.27, 95%CI –5.87 to –2.66, P=0.001), the incidence of pulmonary infection (OR=1.39, 95%CI 1.06 to 1.82, P=0.02), incidence of tube removal (OR=0.11, 95%CI 0.04 to 0.30, P=0.001), incidence of tube blockage (OR=0.47, 95%CI 0.23 to 0.97, P=0.04), incidence of nasopharyngeal discomfort (OR=0.04, 95%CI 0.01 to 0.13, P=0.001), the incidence of nasopharyngeal mucosal damage (OR=0.13, 95%CI 0.04 to 0.42, P=0.008), the incidence of nausea and vomiting (OR=0.20, 95%CI 0.08 to 0.47, P=0.003) were significantly shorter or lower than those of the nasojejunal tube group. The postoperative serum albumin level (MD=5.75, 95%CI 5.34 to 6.16, P=0.001) was significantly better than that of the nasojejunal tube group. However, the intraoperative operation time of the jejunostomy tube group (MD=13.65, 95%CI 2.32 to 24.98, P=0.02) and the indent time of the postoperative nutrition tube (MD=17.81, 95%CI 12.71 to 22.91, P=0.001) were longer than those of the nasojejunal nutrition tube. At the same time, the incidence of postoperative intestinal obstruction (OR=6.08, 95%CI 2.55 to 14.50, P=0.001) was significantly higher than that of the nasojejunal tube group. There were no statistical differences in the length of postoperative hospital stay or the occurrence of anastomotic fistula between the two groups (P>0.05). Conclusion    In the process of enteral nutrition after radical resection of esophageal cancer, jejunostomy tube has better clinical treatment effect and is more comfortable during catheterization, but the incidence of intestinal obstruction is higher than that of traditional nasojejunal tube.

Risk factors for postoperative pulmonary infection in patients with esophageal cancer: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To systematically evaluate the risk factors for postoperative pulmonary infection in patients with esophageal cancer. Methods    CNKI, Wangfang Data, VIP, CBM, PubMed, EMbase, The Cochrane Library were searched from inception to January 2021 to collect case-control studies, cohort studies and cross-sectional studies about risk factors for postoperative pulmonary infection in patients with esophageal cancer. Two researchers independently conducted literature screening, data extraction and quality assessment. RevMan 5.3 software and Stata 15.0 software were used for meta-analysis. Results    A total of 20 articles were included, covering 5 409 patients of esophageal cancer. The quality score of included studies was 6-8 points. Meta-analysis results showed that age (MD=1.99, 95%CI 0.10 to 3.88, P=0.04), age≥60 years (OR=2.68, 95%CI 1.46 to 4.91, P=0.001), smoking history (OR=2.41, 95%CI 1.77 to 3.28, P<0.001), diabetes (OR=2.30, 95%CI 1.90 to 2.77, P<0.001), chronic obstructive pulmonary disease (OR=3.69, 95%CI 2.09 to 6.52, P<0.001), pulmonary disease (OR=2.22, 95%CI 1.16 to 4.26, P=0.02), thoracotomy (OR=1.77, 95%CI 1.32 to 2.37, P<0.001), operation time (MD=14.08, 95%CI 9.64 to 18.52, P<0.001), operation time>4 h (OR=3.09, 95%CI 1.46 to 6.55, P=0.003), single lung ventilation (OR=3.46, 95%CI 1.61 to 7.44, P=0.001), recurrent laryngeal nerve injury (OR=5.66, 95%CI 1.63 to 19.71, P=0.006), and no use of patient-controlled epidural analgesia (PCEA) (OR=2.81, 95%CI 1.71 to 4.61, P<0.001) were risk factors for postoperative pulmonary infection in patients with esophageal cancer. Conclusion    The existing evidence shows that age, age≥60 years, smoking history, diabetes, chronic obstructive pulmonary disease, pulmonary disease, thoracotomy, operation time, operation time>4 h, single lung ventilation, recurrent laryngeal nerve injury, and no use of PCEA are risk factors for postoperative pulmonary infection in patients with esophageal cancer. Due to the limitation of the quantity and quality of included literature, the conclusion of this study still needs to be confirmed by more high-quality studies.

Application of enhanced recovery after surgery in da Vinci robotic McKeown surgery for esophageal cancer: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective     To investigate the application of enhanced recovery after surgery (ERAS) in da Vinci robotic McKeown surgery for esophageal cancer. Methods     Clinical data of patients admitted to the First Hospital of Lanzhou University and undergoing da Vinci robotic McKeown surgery for esophageal cancer from 2017 to 2021 were retrospectively analyzed. According to the treatment, they were divided into two groups, a conventional group and an ERAS group. Patients in the conventional group were treated with the conventional perioperative treatment mode of thoracic surgery, and patients in the ERAS group were treated with accelerated rehabilitation surgical treatment mode. Relevant hospitalization indicators and postoperative complication rates were compared between the two groups. Results     Finally 128 patients were collected, including 106 males and 22 females, with an average age of 61.91 years. There were 71 patients in the conventional group and 57 patients in the ERAS group. The postoperative pain index in the ERAS group was significantly lower than that in the conventional group (P<0.05), and the duration of postoperative analgesic pump used in the ERAS group was shorter than that in the conventional group (2.39±0.49 d vs. 3.13±0.63 d, P<0.001). There was no statistical difference in the incidence of postoperative related complications (gastroesophageal reflux, anastomotic stenosis, anastomotic fistula, arrhythmia, recurrent laryngeal nerve injury, chylothorax, anastomosis stomatitis or incisional infection) between the two groups (P>0.05), but the incidence of postoperative lung infection in the ERAS group was statistically lower (12.28% vs. 26.76%, P=0.043), and the volume of postoperative pleural effusion was statistically less compared with the conventional group (P<0.05). In the ERAS group, the surgery time (294.35±15.19 min vs. 322.79±59.09 min, P<0.001), postoperative exhaust time (1.44±0.39 d vs. 1.94±0.43 d, P<0.001), postoperative removal time of nasolasal tube (6.79±0.73 d vs. 8.21±0.86 d, P<0.001), hospital stay (19.88±3.36 d vs. 21.34±3.59 d, P=0.020), hospitalization costs (105 575.28±8 960.75 yuan vs. 137 894.64±19 518.60 yuan, P<0.001) were all lower or shorter than those of the conventional group. Postoperative activity was longer in the ERAS group than that in the conventional group (P<0.05), but there was no statistical difference in preoperative anesthesia time between the two groups (P=0.841). Conclusion     The application of ERAS in da Vinci robotic McKeown surgery for esophageal cancer can effectively alleviate the physiological and psychological burden of patients, reduce the occurrence of postoperative related complications, effectively shorten the total hospital stay, save hospitalization costs, and reduce the economic burden of patients and society. Therefore, it can be promoted and applied in the clinic.

Accuracy of endoscopy-based artificial intelligence-assisted diagnostic system in the diagnosis of early esophageal cancer: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective     To systematically evaluate the accuracy of endoscopy-based artificial intelligence (AI)-assisted diagnostic systems in the diagnosis of early-stage esophageal cancer and provide a scientific basis for its diagnostic value. Methods    PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang database, VIP database and CNKI database were searched by computer to search for the relevant literature about endoscopy-based AI-assisted diagnostic systems for the diagnosis of early esophageal cancer from inception to March 2022. The QUADAS-2 was used for quality evaluation of included studies. Meta-analysis of the literature was carried out using Stata 16, Meta-Disc 1.4 and RevMan 5.4 softwares. A bivariate mixed effects regression model was utilized to calculate the combined diagnostic efficacy of the AI-assisted system and meta-regression analysis was conducted to explore the sources of heterogeneity. Results    A total of 17 articles were included, which consisted of 13 retrospective cohort studies and 4 prospective cohort studies. The results of the quality evaluation using QUADAS-2 showed that all included literature was of high quality. The obtained meta-analysis results revealed that the AI-assisted system in the diagnosis of esophageal cancer presented a combined sensitivity of 0.94 (95%CI 0.91 to 0.96), a specificity of 0.85 (95%CI 0.74 to 0.92), a positive likelihood ratio of 6.28 (95%CI 3.48 to 11.33), a negative likelihood ratio of 0.07 (95%CI 0.05 to 0.11), a diagnostic odds ratio of 89 (95%CI 38 to 208) and an area under the curve of 0.96 (95%CI 0.94 to 0.98). Conclusion    The AI-assisted diagnostic system has a high diagnostic value for early stage esophageal cancer. However, most of the included studies were retrospective. Therefore, further high-quality prospective studies are needed for validation.