Search

Dysregulation of long non-coding RNAs (lncRNAs) and interferon signaling contributes to tumorigenesis and progression; however, their crosstalk in tumor biology remains poorly understood. Here, we showed that TSPEAR-AS2, an lncRNA mediated by METTL1, activates the interferon signaling pathway in esophageal cancer (ESCA). Clinically, we conducted a pan-cancer investigation and identified TSPEAR-AS2 as a novel ESCA-related lncRNA that predicts a worse patient prognosis. The high expression of TSPEAR-AS2 was validated in multiple ESCA cohorts, demonstrating that this lncRNA had good diagnostic performance. METTL1, an RNA N7-methylguanosine (m7G) methyltransferase, was positively correlated with TSPEAR-AS2 expression in ESCA tissues, and METTL1 was found to induce TSPEAR-AS2 expression in ESCA cells. Functionally, the up-regulation of TSPEAR-AS2 promoted proliferation, cell cycle progression, migration, and stemness in ESCA cells, whereas its knockdown attenuated these malignant phenotypes. Furthermore, both TSPEAR-AS2 deficiency and antisense oligonucleotide (ASO)-based intratumoral intervention could significantly suppress tumor growth in vivo. Mechanistically, quantitative proteomic analysis revealed that TSPEAR-AS2 ablation altered the expression of functional proteins related to interferon signaling pathways, such as HLA-E, IRF3, and IFITs. These findings identify a previously unrecognized role of the METTL1/TSPEAR-AS2/interferon signaling axis in ESCA development and suggest that TSPEAR-AS2 is a potential prognostic indicator and therapeutic vulnerability for this malignancy. [ABSTRACT FROM AUTHOR]

Background: There are currently limited real-world data on the effectiveness and safety of first-line pembrolizumab combined with chemotherapy in patients with advanced/recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in China. This study was conducted to address this knowledge gap. Methods: This multicenter retrospective cohort study was conducted at 17 hospitals in China and included adults (⩾18 years) with stage IV primary ESCC, or recurring 6 months after radical radiotherapy/surgery-based combination therapy, who had received first-line pembrolizumab plus chemotherapy. Data were collected from electronic medical records. Endpoints included objective response rate (ORR), disease control rate (DCR) progression-free survival (PFS), overall survival (OS), and safety. Subgroup analyses were conducted to identify patient characteristics and treatment patterns associated with treatment response. Results: In total, 202 patients who had received treatment from 2018 to 2023 were included: 125 (61.9%) newly diagnosed and 77 (38.1%) with recurrence, 181 (89.1%) were male. Pembrolizumab was most commonly combined with paclitaxel + platinum (69.8%) or fluorouracil + platinum (19.3%). After a median follow-up of 22.6 months (95% confidence interval (CI) 20.1–25.4), the ORR and DCR were 60.9% and 87.6% and the median PFS and OS were 10.8 months (95% CI 9.1–13.5) and 17.3 months (95% CI 14.9–19.9), respectively. OS was similar in patients with treatment-naïve and recurrent disease. Among the combination chemotherapy regimens, paclitaxel + platinum was associated with the longest median OS (18.2 months, 95% CI 16.1–22.5). Favorable survival outcomes were observed in patients with oligometastases. No new safety signals were observed. Conclusion: These real-world data indicate that the first-line treatment with pembrolizumab plus chemotherapy is effective and safe in Chinese patients with advanced ESCC and show that paclitaxel + platinum is the most commonly used and most effective partner chemotherapy in China. [ABSTRACT FROM AUTHOR]

Maize flour is the staple food in many African countries, which is often contaminated with mycotoxin‐producing fungi. In this study, fungal contamination and the concentrations of fumonisins B1 and B2 in different types of maize flour in Malawi were examined, and the risk of mycotoxicosis, including endemic cancer, development was assessed. Data on the maize flour consumption of 187 Malawians were collected using a self‐generated questionnaire. Fifty‐nine samples of four differently processed types of flour from home‐grown maize were collected and screened for mycotoxins using high‐performance liquid chromatography–mass spectrometry (HPLC‐MS). Fumonisin B1 and B2 concentrations in maize flour and daily individual intakes were quantified by combined accelerated solvent extraction, solid phase extraction, and HPLC‐MS detection. The fumonisin concentrations ranged from 0.00 to 10,306.65 μg/kg maize, with a median concentration of 230.20 μg/kg (interquartile range (IQR), 592.77), and differed significantly among the four flour types. The median daily intake of fumonisins B1 and B2 per kilogram body weight was 3.01 μg (IQR, 6.47) and was significantly greater for deya flour (8.17 μg (IQR, 12.84)) than for mgaiwa flour (3.73 μg (IQR, 6.23); p = 0.046), gramil flour (1.08 μg (IQR, 2.39); p = 0.030), and white flour (1.18 μg (IQR, 2.78); p = 0.002). This intake exceeded the legitimate upper limit in 75% of individuals, by about nine times on average. The reduction of fumonisin intake is crucial to lower the associated disease risk and burden and can be achieved by changing the kernel processing method, improving storage conditions, and introducing sorghum and millet as possible staple food alternatives in Malawi. [ABSTRACT FROM AUTHOR]

Background and objectives: Currently, research on the role of B cells in esophageal cancer (EC) is limited, and existing studies on their impact are controversial. Therefore, this study was conducted to elucidate the complex causal relationship between B cells and EC, expand the understanding of esophageal cancer immunology. Methods: Bidirectional two-sample Mendelian randomization (MR) was performed to assess the causal relationships between 190 B cell phenotypes and EC. To complement the MR analysis, Bayesian Weighted Mendelian Randomization (BWMR) was employed, and sensitivity analyses were conducted to evaluate the robustness of the findings. Positive results were further validated in independent cohorts of esophageal cancer studies. In addition, RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) were utilized for validation, incorporating B cell-related gene expression analysis and functional enrichment analysis to support the MR findings. Results: In the primary analysis, significant causal relationships were observed between 5 B cell types and the risk of EC; the onset of EC was causally linked to 3 B cell phenotypes. Validation in other cohorts revealed that 4 outcomes aligned with the primary analysis, included were CD19 on IgD + CD38-, CD20 on IgD- CD27-, CD20 on IgD- CD38br, and CD38 on PB/PC. Further validation using RNA-seq data showed that CD38 mRNA was significantly overexpressed in EC tissues, whereas CD19 and MS4A1 mRNA levels did not differ significantly between tumor and normal tissues. Functional enrichment analysis revealed that CD19, MS4A1, and CD38 are involved in multiple tumor-related immune pathways, suggesting their pivotal role in regulating the tumor immune microenvironment. Conclusions: Our study suggests a potential connection between B cell phenotypes and EC through bidirectional two-sample MR combined with BWMR analysis, providing a preliminary basis for future research. [ABSTRACT FROM AUTHOR]

Oesophageal cancer is the seventh leading cause of cancer mortality worldwide. Two major pathological subtypes exist: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Epidemiological studies in the last decade have shown a gradual increase in the incidence of oesophageal adenocarcinoma worldwide. The prognosis of oesophageal cancer has greatly improved due to breakthroughs in screening, surgical procedures, and novel treatment modalities. The success achieved with combined modality therapies, including surgery, chemotherapy, and radiotherapy, to treat locally advanced oesophageal cancer is particularly notable. Immunotherapy has become a crucial treatment for oesophageal cancer, with immune checkpoint inhibitor-based therapies now established as the standard of care in adjuvant and metastatic first-line settings. This Seminar provides an overview of advances in the screening, diagnosis, and treatment of oesophageal squamous cell carcinoma and oesophageal adenocarcinoma, with a particular focus on neoadjuvant therapies for locally advanced oesophageal cancer and immune checkpoint inhibitor-based therapies. [ABSTRACT FROM AUTHOR]

Introduction: The delays in cancer therapies have the potential to impact disease progression by allowing the unchecked growth and spread of cancer cells. However, the understanding of the association between treatment waiting time and survival outcomes in patients with esophageal cancer (EC) is limited. This study aims to assess the impact of waiting time on survival outcomes among EC patients in Hebei province, which is recognized as one of the high-risk areas for EC in China. Methods: A total of 9,977 non-metastatic EC patients who underwent surgical treatment were identified between 2000 and 2020. The survival outcomes of overall survival (OS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier methodology. Univariate and multivariate Cox regression analysis was employed to evaluate the impact of treatment delays on OS and CSS. Results: The average delay time for initiating EC surgical treatment after diagnosis was 1.31 months (95%CI=1.29–1.34). Patients with a long delay (≥ 3 months) in treatment, comprising 9977 EC patients, exhibited significantly lower rates of 3-, 5-, and 10-year OS and CSS compared to those without any delay in treatment initiation. A long delay in EC treatment independently associated with an elevated risk of all-cause and cancer-cause mortality among various patient subgroups, including males, older individuals, single individuals, low-income patients, residents of nonmetropolitan counties, as well as those diagnosed with poorly differentiated and stage IV EC. Discussion: The long delay of treatment initiation impacts the outcomes of OS and CSS in EC patients. Optimizing treatment timing may enhance life expectancy for individuals diagnosed with EC. [ABSTRACT FROM AUTHOR]

Introduction: Recently, the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system was updated for its 8th edition. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a useful imaging tool to diagnose and predict prognoses for esophageal cancer. However, there was no previous study to explore the role of FDG PET/CT in the staging system based on the 8th edition. The prognostic value of FDG PET/CT was investigated in patients with esophageal squamous cell carcinoma (SqCC) considering the new 8th AJCC/UICC staging system. Methods: Subjects were 721 patients with esophageal SqCC undergoing pretherapeutic FDG PET/CT. Clinico-pathological variables and the maximum standardized uptake value (SUVmax) of the primary tumor were included in survival analysis. Subgroup analysis was performed to compare hazard ratios according to pathological stage and SUVmax. A new staging classification including FDG uptake was proposed. Results: In multivariate survival analysis, pathological stage and SUVmax of the primary tumor were selected as independent prognostic factors for overall survival in both the 7th and 8th editions. The proposed new staging system showed better discrimination for overall survival between stage I and II than did the conventional staging system (hazard ratios: 2.250 vs. 1.341). Conclusions: The FDG uptake of the primary tumor was found to be an independent prognostic factor along with pathological stage based on both 7th and 8th AJCC/UICC staging systems in patients with esophageal SqCC. The suggested new staging system including SUVmax was better for predicting prognoses than the conventional staging system. [ABSTRACT FROM AUTHOR]

Objective To observe the effect of preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer on lung function and mRNA expression of GATA-binding protein 3 (GATA3) and forkhead protein P3 (Foxp3) in peripheral blood. Methods Sixty esophageal cancer patients who underwent modified Ivor-Lewis surgery in our hospital from January 2022 to October 2023 were selected and divided into two groups by simple random method. The control group was given conventional diet before operation, and the observation group was given enteral nutrition support before operation. The two groups were compared in terms of nutritional support. Results Both groups showed significantly decreases in one-second exertion expiratory volume/exertion lung volume (FEV1IFVC) (P < 0.05), FVC (P < 0.05 ), FEV1 (P < 0.05) and the levels of peripheral blood GATA3 (P < 0.05), Foxp3 mRNA (P < 0.05) expression compared with those at admission (P < 0.05), but no significant differences in pulmonary function (P > 0.05), peripheral blood GATA3 (P > 0.05), and Foxp3 mRNA (P > 0.05) expression between them at 1 week postoperatively. Both groups exhibited significantly lower levels of albumin, prealbumin, haemoglobin, transferrin, PNI and body mass and body mass index at admission as compared to those at one week after surgery (P < 0.05). The observation group showed significantly higher levels of albumin, prealbumin, haemoglobin, transferrin, and PNI at 1 week postoperatively (P < 0.05), but no significant differences in ventilation time, defecation time, drain retention time, hospitalisation time, and complication rate as compared to the control group (P > 0.05). Conclusion Preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer improves postoperative nutritional status, and renders less effect on postoperative lung function and peripheral blood GATA3 and Foxp3 mRNA expression. [ABSTRACT FROM AUTHOR]

The goal of this study was to compare the advantages of conventional laparoscopic surgery (CLS) and the split-leg supine position single-port plus one laparoscopic surgery (SSP SILS + 1) in esophageal surgery. This study enrolled 73 patients who previously underwent radical esophagectomy for esophageal cancer from August 2021 to February 2023. Among them, 36 patients underwent SSP SILS + 1, whereas the remaining 37 patients underwentCLS. Surgical time, bleeding volume, number of dissected lymph nodes, incision length, and postoperative abdominal pain score between the two groups of patients were compared using either the Student's t-test or chi-square test. Time of abdominal incision (1.4 ± 0.2 min vs. 5.2 ± 0.7 min, p < 0.001) was shorter in patients in the SSP SILS + 1 group compared with those in the CLS group. However, the average incision length was shorter in the SSP SILS + 1 group compared with that in the CLS group (35.4 ± 4.0 cm vs. 4.6 ± 4.1 cm, p < 0.001). Notably, the pain score on postoperative day (POD) 1 was lower in the SSP SILS + 1 group compared with that in the CLS group (5.7 ± 0.7 vs.6.3 ± 0.7, p = 0.001). The SCAR score was also lower in the SSP SILS + 1 group compared with that in the CLS group (3.5 ± 0.9 vs. 8.3 ± 1.4, p = 0.019). There was no significant difference in the number of dissected abdominal lymph nodes and positive lymph nodes (p > 0.01) between the two groups. The SSP SILS + 1 intervention offers multiple benefits over conventional surgical procedures, encompassing shorter incision length and pain scores on POD 1. In accelerated rehabilitation surgery for esophageal cancer, this surgical procedure demonstrated high safety, feasibility. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To analyze the pattern of lymph node metastasis in esophageal cancer based on the theory of membrane anatomy.A retrospective analysis was conducted on 143 patients who underwent esophageal surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences from March 2021 to March 2022. Lymph node metastasis was observed and categorized according to postoperative T staging. The characteristics and patterns of lymph node metastasis in different regions were observed, and the lymph node metastasis patterns in patients with clinical T3 esophageal cancer were analyzed using membrane anatomy theory.Among the 143 patients with esophageal squamous cell carcinoma, 21 were treated with surgery alone, while the rest received preoperative adjuvant therapy. A total of 5456 lymph nodes were cleared from the 143 patients, with 204 positive lymph nodes, resulting in a positive rate of 3.74%. In the thoracic lymph node dissection, the metastatic rates exceeded 5% for the following regions: 106recR (17.36%), 106recL (12.5%), 107 (10.42%), and 108 (5.56%) station. When analyzing the abdominal lymph node metastasis, the metastatic rates exceeded 5% for regions 7 (13.19%), 3a (7.64%), 2 (6.94%), and 1 (6.25%) station. Group analysis of patients with esophageal squamous cell carcinoma before postoperative pathological T3 stage revealed an increasing trend in tumor lymph node metastasis rate with later T staging. Lymph node metastasis in region 106recR can occur early, with a metastasis rate of 18.37% in T1 tumors. Analysis of lymph node metastasis characteristics in 103 patients clinically staged as T3 showed that 3966 lymph nodes were cleared, with 186 positive nodes, resulting in a positive rate of 4.69%. Lymph node metastasis rates were higher in regions 106recL, 106recR, 107, 108, 110, 1, 2, 3a, and 7, all exceeding 5%.The theory of membrane anatomy can effectively explain the pattern of lymph node metastasis in esophageal cancer. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) poses a substantial threat to human health. The development of radioresistance in esophageal cancer cells is a critical factor contributing to local treatment failure and an unfavorable prognosis in affected patients. A comprehensive analysis was performed using bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) data from esophageal squamous cell carcinoma (ESCC) samples. Radioresistant ESCC cell lines were generated to explore the functional role of CCNG1. Various techniques, including gene knockdown, flow cytometry, and apoptosis assays, were utilized to evaluate alterations in radiosensitivity, cell cycle progression, and cell survival in response to CCNG1 modulation. Elevated CCNG1 expression was associated with poor clinical outcomes in ESCC patients and contributed to various malignant phenotypes in ESCC cells. In radioresistant ESCC cell lines, CCNG1 knockdown markedly increased radiosensitivity, as demonstrated by enhanced G2/M phase arrest and apoptosis following radiation exposure. CellChat analysis indicated a correlation between CCNG1 and the Wnt/β-catenin signaling pathway, while western blot (WB) analysis confirmed that CCNG1 functions as a downstream effector of Wnt/β-catenin. Our study has identified CCNG1 as a key regulator of radiosensitivity in ESCC, mediated through its interaction with the Wnt/β-catenin signaling pathway. Targeting the Wnt/β-catenin/CCNG1 axis presents a promising therapeutic strategy to enhance the efficacy of radiotherapy in ESCC, potentially overcoming radioresistance and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Sulfur microbial diet (SMD) is a dietary pattern closely related to the intestinal load of sulfur-metabolizing microbes in humans. Diet and microbes may play an important role in the carcinogenesis of esophagus. However, epidemiological studies on SMD and esophageal cancer (EC) risk are scarce. Here, we evaluated this association based on a large American cohort. Methods: In the cohort of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a SMD score was calculated to evaluate participants' compliance of SMD pattern, with higher scores presenting greater adherence. Cox hazards regression model was used to explore the association between the SMD score and the incidence of EC, esophageal squamous cell carcinoma (ESCC), and esophageal adenocarcinoma (EA). Subgroup analyses were conducted to figure out potential modifiers interacting with SMD on EC. Sensitivity analyses were used to testify the robustness of our main result. Results: Among 101,752 participants, 154 EC cases, consisted of 41 ESCC cases and 97 EA cases, were identified with mean follow-up of 8.9 years. In the fully adjusted model, the highest versus the lowest quartiles of the SMD score were found to be associated with an increased risk of EC and ESCC (EC: HRQ4 vs. Q1: 1.64; 95% CI: 1.05, 2.56; P = 0.016 for trend; ESCC: HRQ4 vs. Q1: 2.37; 95% CI: 1.02, 5.47; P = 0.031 for trend), while not significantly associated with increases risk of EA (HRQ4 vs. Q1: 1.41; P = 0.144 for trend). The main result remained through a series of sensitivity analyses. Subgroup analyses showed a stronger association between SMD and EC in participants with no regular consumption of aspirin (HRQ4 vs. Q1: 1.90; 95% CI: 1.04, 3.47) than in those using aspirin regularly (HRQ4 vs. Q1: 1.37; 95% CI: 0.71, 2.66) (P = 0.008 for interaction). Conclusion: Adherence to the SMD pattern may be associated with increased risks of EC and ESCC, particularly for EC in individuals who do not regularly consume aspirin. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions In immunochemical fecal occult blood test (iFOBT) positive subjects, colonoscopy screening can detect colorectal cancers and advanced adenomas, yet most iFOBT‐positive subjects find no relevant lower gastrointestinal lesions. Limited data are available on upper gastrointestinal (UGI) cancer risk in iFOBT‐positive patients. This study investigated the incidence of UGI malignancies diagnosed within 3 years post‐colonoscopy after a positive iFOBT.Retrospective analysis of iFOBT‐positive patients aged 50–75 years who underwent a colonoscopy at a single institution. All patients with a diagnosis of UGI cancer within 3 years post‐colonoscopy were identified by linking with the Queensland Cancer Register. This was used to compare to the geographical population aged 50–74 years based on the Australian Bureau of Statistics and Queensland Cancer Council data.From 1748 eligible participants, 0.23% (95% confidence interval [CI] 0.06–0.58) were diagnosed with UGI cancer within 3 years post‐colonoscopy. This indicates an esophageal cancers rate of 114.42 per 100 000 (95% CI 100.56–298.28) and gastric cancer rate of 57.21 per 100 000 (95% CI 55.76–261.12). Of the patients with a UGI cancer, 75% would have had an unexplained iFOBT. Annual incidence for the same geographic region, ages, and period for the combined esophageal and gastric cancer was 36.08 per 100 000 (95% CI 32.87–39.52).Among individuals with a positive iFOBT in a bowel cancer screening program, the rates of gastric and esophageal cancers were 2.7 and 7.5 times higher than the general population. Adding gastroscopy to a colonoscopy for iFOBT‐positive patients in cancer surveillance programs may be justifiable. [ABSTRACT FROM AUTHOR]

Esophageal cancer is one of the most common cancers in the world, ranking sixth in cancer-related mortality. Doxorubicin (DOX), as a classic broad-spectrum, non-specific small-molecular anti-tumor drug, has achieved widespread use, including in the treatment of esophageal cancer. However, due to its strong cardiotoxicity, poor tumor-targeting ability, and short half-life, the clinical application of DOX has been greatly limited. In this research, we designed and successfully synthesized a peptide sequence IEIIIK (IEK for short) with excellent pH responsiveness. Under physiological conditions (pH 7.4), the peptide can encapsulate DOX and self-assemble into a stable hydrogel (DOX-IEK) through hydrophobic and electrostatic interactions. After being injected into the acidic tumor microenvironment, the protonation degree of alkaline amino acid lysine increased and the negative charge of glutamate decreased, directly leading to enhanced electrostatic repulsion and subsequent hydrogel dissociation. Released DOX can accumulate in tumor tissue and achieve anti-tumor efficacy. More importantly, the hydrogel can act as a drug reservoir for sustained drug release, improving the drug targeting ability, prolonging the duration of drug administration to compensate for the short half-life of DOX, and reducing systemic toxicity. Ideal anti-tumor efficacy has been achieved in both the in vitro and in vivo experiments. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors (ICIs) have transformed advanced gastric cancer treatment, yet patient responses vary, highlighting the need for effective biomarkers. Common markers, such as programmed cell death ligand-1 (PD-L1), microsatellite instability/mismatch repair (MSI/MMR), tumor mutational burden, tumor-infiltrating lymphocytes, and Epstein–Barr virus, face sampling challenges and high costs. This study seeks practical, minimally invasive biomarkers to enhance patient selection and improve outcomes. Methods: This multicenter retrospective study analyzed 617 patients with advanced gastric or gastroesophageal junction cancer treated with programmed cell death protein-1 (PD-1)/PD-L1 inhibitors from January 2019 to March 2023. Clinical data and peripheral blood marker data were collected before and after treatment. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included the objective response rate (ORR) and disease control rate (DCR). Least absolute shrinkage and selection operator (LASSO)-Cox and LASSO logistic regression analyses identified independent factors for OS, PFS, and ORR. Predictive nomograms were validated using receiver operating characteristic (ROC) curves, areas under the curve (AUCs), C-indices, and calibration curves, with clinical utility assessed via decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: OS-related factors included treatment line, T stage, ascites, pretreatment indirect bilirubin (pre-IBIL), posttreatment CA125, CA199, CA724, and the PLR. PFS-related factors included treatment lines, T stage, metastatic sites, pre-IBIL, posttreatment globulin (GLOB), CA125, and CA199 changes. ORR-related factors included treatment line, T stage, N stage, liver metastasis, pretreatment red cell distribution width-to-platelet ratio (RPR), CA125, and CA724 changes. The nomograms showed strong predictive performance and clinical utility. Conclusions: Early treatment, lower T stage, the absence of ascites, and lower pre-IBIL, post-CA125, CA199, CA724, and PLR correlate with better OS. Factors for improved PFS include early treatment, lower T stage, fewer metastatic sites, and lower pre-IBIL, post-GLOB, and post-CA125 levels. Nomogram models can help identify patients who may benefit from immunotherapy, providing valuable clinical guidance. [ABSTRACT FROM AUTHOR]

The catalytic hairpin assembly (CHA)-based miRNA detection methods have garnered significant attention due to their simplicity and acceptable amplification efficiency. However, these methods necessitate improved sensitivity. In this work, we present a colorimetric and ultrasensitive approach for the detection of cancer-related miRNAs which is initiated by CHA-mediated nicking endonuclease-assisted signals recycling. The target initiates the CHA process to expose the functional section in the P2 probe. This section can activate cascaded recycling cycles to produce numerous linker sequences by Nt.AlwI endonuclease-assisted cleavage of two hairpin signal probes. The 3,3',5,5'-tetramethylbenzidine sulfate (TMB)/H2O2-based color reaction is induced by the fixation of the cDNA-HRP on the surface of magnetic beads, which is mediated by the linker sequence. The proposed method demonstrates a sensitivity that is either comparable to or superior to that of previous colorimetric miRNA detection methods, as a result of this design. Furthermore, the method demonstrated a promising potential for clinical applications and a high selectivity to target miRNA. Consequently, it provides a colorimetric assay that is both ultrasensitive and dependable for the visual detection of miRNA, which has the potential to revolutionize the early diagnosis of cancer. [ABSTRACT FROM AUTHOR]

Background: Gastro-tracheal fistula is a rare but serious complication after esophageal surgery, often requiring long-term treatment and invasive procedures. Gastro-tracheal fistula usually occurs through the posterior mediastinal route and rarely through the retrosternal route. No previous reports have described gastro-tracheal fistula after retrosternal route reconstruction was cured by conservative treatment. Case presentation: A 70-year-old man with lower thoracic esophageal cancer underwent thoracoscopic esophagectomy in the prone position and gastric tube reconstruction through the retrosternal route with neck anastomosis after neoadjuvant chemotherapy. Despite anastomotic leakage on postoperative day 10, his general condition was stable, and he was managed conservatively with antibiotics and gastric tube decompression. On day 29, he presented with high fever and a gastro-tracheal fistula was observed by esophagography. Conservative management was continued because the patient remained stable. On day 48, esophagography showed that the fistula was undetectable. The patient was able to take fluids orally. He progressed well on an oral diet and was transferred to a different hospital. Conclusions: A gastro-tracheal fistula, although rare, can occur after retrosternal route reconstruction. When a patient is stable, gastro-tracheal fistula after retrosternal route reconstruction may be cured by conservative treatment. [ABSTRACT FROM AUTHOR]

Background: In advanced-stage esophageal squamous cell carcinoma (ESCC), treatment of both the primary tumor and metastatic sites is imperatively required. Consequently, an optimal treatment modality should effectively control both aspects. Therefore, the benefits of concurrent chemoradiotherapy (CCRT) in cases of advanced-stage ESCC should be evaluated. Methods: This retrospective study compared the efficacy and safety of CCRT versus chemotherapy alone for advanced-stage ESCC patients from January 2012 to December 2023 at a university hospital in Southern Thailand. Survival was assessed using the Kaplan–Meier approach, with comparisons being made by the log-rank test. A p-value of <0.05 indicated statistical significance. Results: From a total of 196 patients with stage IV ESCC, 117 (59.7%) received CCRT, while 79 (40.3%) received chemotherapy alone. The median overall survival (OS) time was 9.04 months for CCRT and 5.79 months for chemotherapy (hazard ratio, HR: 0.58 [0.43–0.78]). CCRT significantly improved OS time in stage IVA patients (HR: 0.52 [0.29–0.93]), but not in stage IVB patients (HR: 0.76 [0.51–1.11]). The median progression-free survival (PFS) time was 6.04 months for CCRT and 3.50 months for chemotherapy (HR 0.48 [0.35–0.65]). The objective response rates (ORRs) were 43.6% and 22.8%, respectively (p = 0.003). Hematological toxicities were more common with CCRT, along with mild cases of treatment-associated pneumonitis and dermatitis. Conclusions: Although palliative chemotherapy is the standard treatment for advanced-stage ESCC, CCRT provides significant benefits for patients with stage IVA ESCC, improving OS, PFS, and ORRs, despite there being a higher incidence of adverse events. Thus, CCRT should be considered for patients with stage IVA ESCC with a good performance status. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the fecal and tumor microbiome as potential biomarkers of tumor response to neoadjuvant immunotherapy in combination with chemoradiation. We performed 16S rRNA amplicon sequencing on fecal and tumor samples, as well as fecal metabolomics, on biosamples collected from patients with resectable esophageal or gastroesophageal junction carcinoma before and during treatment. The fecal microbiome of patients whose tumors achieved a pathologic complete response revealed enrichment in sphingolipid and primary bile acids, with corresponding elevated abundance of several bacterial species: Roseburis inulinivorans, Ruminococcus callidus, and Fusicantenibacter saccharivorans. While these results provide initial insight, further study is necessary to validate these data and determine how microbes alter the immune response with neoadjuvant immunotherapy. Background: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer. Methods: Fecal and tumor samples were collected from patients with stage II–III resectable esophageal or gastroesophageal junction carcinoma treated with neoadjuvant immune checkpoint inhibitors (ICIs) plus CRT prior to surgical resection. Microbiome profiles were analyzed by 16S rRNA amplicon sequencing and taxonomic data were integrated with fecal metabolite analysis to assess microbial function. Results: The fecal microbiome of patients with pathological complete response (PCR) grouped in distinct clusters compared to patients with residual viable tumor (RVT) by Bray–Curtis diversity metric. Integrated taxonomic and metabolomic analysis of fecal samples identified a sphingolipid and primary bile acid as enriched in the PCR, the levels of which correlated with several bacterial species: Roseburis inulinivorans, Ruminococcus callidus, and Fusicantenibacter saccharivorans. Analysis of the tumor microbiome profiles identified several bacterial genera previously associated with esophageal tumors, including Streptococcus and Veillonella. Conclusions: These results further characterize the fecal and tumor microbiome of patients with operable esophageal cancer and identify specific microbes and metabolites that may help elucidate how microbes contribute to tumor response with neoadjuvant CRT combined with ICI. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the role of three specific proteins—FGF8, ALK, and EML4—in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC), a common type of esophageal cancer. The aim of the study was to assess whether the presence and levels of these proteins could indicate which patients are at a higher risk of poor survival following surgery. By analyzing tissue samples from 122 patients, who underwent surgical removal of their cancer, the study discovered that an increase in FGF8 protein levels is associated with a reduced chance of survival. Additionally, the study found a significant correlation between FGF8 and alterations in the ALK and EML4 proteins. These results suggest that FGF8 could serve as a valuable marker for predicting patient outcomes and might also become a target for future therapies aimed at improving survival rates in ESCC patients. FGF8, ALK, and EML4 have been identified as promising biomarkers in a number of malignancies. The aim of this study was to examine the prognostic role of FGF8, ALK, and EML4 in esophageal squamous cell carcinoma (ESCC). Methods: Consecutive patients with ESCC who underwent upfront resection were included in this study. ALK and EML4 gene status was evaluated by fluorescence in situ hybridization (FISH) using a triple-color break-apart single-fusion probe and a probe against 2p11. FGF8, ALK, and EML4 protein expression was determined by immunohistochemistry. Results: A total of 122 patients were included in this study. Multivariate analysis revealed that FGF8 overexpression is an independent negative prognostic factor for patients' overall survival (OS) (p = 0.04). Furthermore, a significant correlation between the expression of FGF8, and ALK (p = 0.04) and EML4 (p = 0.01) alteration was found. Conclusions: FGF8 overexpression is an adverse independent prognostic factor in patients with upfront resected ESCC. Furthermore, FGF8 expression significantly correlates with ALK and EML4 amplification and may therefore qualify as a future therapeutic target. [ABSTRACT FROM AUTHOR]

Introduction: Identifying accurate biomarkers for predicting response to chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) is a critical challenge. The protein SIRT1, recognized for its implications in longevity, has been associated with tumor promotion in ESCC. However, data regarding its correlation with CRT sensitivity remain unreported. Therefore, in this study, we aimed to investigate the relationship between SIRT1 expression and CRT sensitivity and concurrently assess the effect of SIRT1 knockdown on CRT sensitivity in ESCC. Methods: This study included 73 patients who underwent radical esophagectomy after CRT. SIRT1 expression in pre-treatment endoscopic biopsies was assessed through immunostaining, followed by a comparative analysis of CRT effects on surgical specimens. Small interfering RNA was used to attenuate SIRT1 expression in TE5 and TE10 cells, which were then subjected to cisplatin treatment at varying doses and concentrations and irradiation with X-rays, respectively. Results: High SIRT1 tissue expression was significantly associated with CRT resistance. Multivariate analysis identified high SIRT1 expression as an independent biomarker for poor CRT response. In TE-5 and TE-10 cells, SIRT1 knockdown significantly decreased cell viability and increased sensitivity to cisplatin and radiation treatment compared to that of the negative control. Conclusion: Our study results demonstrate the potential of SIRT1 as a predictive biomarker for CRT response in ESCC, highlighting the heightened sensitivity to CRT upon the transcriptional inactivation of SIRT1. Targeting SIRT1 emerges as a promising strategy for enhancing the efficacy of CRT for ESCC. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer poses a significant health burden globally. Endoscopic treatment has emerged as a viable option for patient ineligible for surgery or experiencing disease recurrence post-radiotherapy. Methods: Patients visiting the Department of Endoscopy at the Cancer Hospital of China Academy of Medical Sciences between March 2009 and March 2024 were retrospectively analyzed. Inclusion criteria encompassed patients with histologically confirmed esophageal cancer who had not undergone surgery, but received radiotherapy or CRT, and subsequently opted for endoscopic treatment. Data on demographics, treatment modalities, recurrence patterns, histopathological characteristics, and outcomes were collected. Statistical analysis was conducted using SPSS 27.0, employing Kolmogorov–Smirnov tests for data normality assessment. Results: Out of 25 included patients, the mean age was 60.29 years, with a predominance of males (88%). Most patients (64%) received chemoradiotherapy (CRT), while the rest underwent radiotherapy alone. The median follow-up duration was 50.92 months, with a median recurrence time of 38.92 months. Majority (56%) presented with a solitary lesion and 76% had negative margins. Histopathological analysis revealed various stages of cancer, with the most common being high-grade squamous epithelial neoplasia (64%). Survival analysis indicated a 72% overall survival rate, with 16% surviving beyond 5-year post-treatment. Approximately, 20% succumbed during the study, primarily due to non-esophageal causes (16%). Conclusion: Endoscopic treatment shows promise as a therapeutic option for selected esophageal cancer patients, offering favorable outcomes in terms of survival and disease control. Further prospective studies are warranted to validate these findings and optimize patient selection criteria for endoscopic interventions in esophageal cancer management. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the relationship between preoperative arterial calcifications and postoperative outcomes after Ivor Lewis esophagectomies. Methods: This was a single-center retrospective review of Ivor Lewis esophagectomies from 2013 to 2018. Preoperative CT imaging was reviewed, and arterial calcifications were graded (absent, minor, or major) in various locations. The primary outcome included major complications (defined by the Clavien-Dindo classification III–V) and the secondary outcomes were 90-day reoperations, readmissions, and mortality. Significant associations (p < 0.05) between calcifications and outcomes on univariable analysis were evaluated using a multivariable logistic regression model (odds ratios, OR; 95% confidence intervals, CI). Results: One hundred patients underwent esophagectomies from 2013 to 2018 (79% male, 90% White, median age 68 years), and 85% were classified as ASA III. Ninety-four patients had accessible preoperative imaging. Arterial calcifications in specific areas were observed: 82 in coronary arteries (major in 33 patients), 54 in the aortic valve, 78 in supra-aortic arteries, 79 in the thoracic aorta, 82 in the abdominal aorta, and 71 in common iliac. Furthermore, 60 patients exhibited celiac axis calcifications, with 40 patients classified as major. Twenty-five patients experienced major complications. Anastomotic leak occurred in two patients, and graft necrosis occurred in one patient. Ninety-day readmission was 10%, reoperation was 12%, and mortality was 4%. On univariable analysis, major coronary artery calcifications were significantly associated with major complications (OR 4.04; 95% CI 1.34–12.16; p = 0.02) and 90-day readmissions (OR 8.20; 95% CI 1.01–68.47; p = 0.04). However, no significant associations were identified between 90-day reoperations or mortality and arterial calcifications. Conclusions: This study demonstrated that preoperative coronary calcifications increase the risk of postoperative complications, as this may be a surrogate of overall health. Nonetheless, the correlation between splanchnic calcifications and postoperative outcomes needs further exploration. [ABSTRACT FROM AUTHOR]

Esophageal cancer presents a clinical challenge due to its high incidence and unfavorable prognosis. The prognostic role of the circumferential resection margin (CRM) remains highly controversial, potentially due to its temporal dynamics coupled with variability in follow-up durations across studies. We aimed to explore the time-dependent prognostic significance of CRM in T3 esophageal squamous cell carcinomas (ESCCs). We systematically reviewed literature from 1990 to 2023 to determine how follow-up duration influences the prognostic role of CRM in esophageal cancer. Concurrently, we performed a retrospective examination of 354 patients who underwent treatment at the National Cancer Center between 2015 and 2018. Integrating a time interaction term in the Cox regression analyses enabled us to not only identify independent risk factors affecting overall survival (OS) but also to specifically scrutinize the potential temporal variations in CRM's prognostic impact. Our literature review suggested that CRM's influence on prognosis diminishes with longer follow-up durations for both classifications, namely the Royal College of Pathologists (RCP) (β = −0.003, P  < 0.001) and the College of American Pathologists (CAP) (β = −0.007, P  < 0.001). Time-dependent multivariate Cox regression analysis emphasized the evolving nature of CRM's prognostic effect, and the inclusion of the time interaction term enhanced model accuracy. In conclusion, CRM is an independent prognostic factor for T3 thoracic ESCC patients. Its influence appears to decrease over extended follow-up periods, shedding light on the heterogeneity seen in previous studies. With the time interaction term, CRM becomes a more precise post-operative prognostic indicator for esophageal cancer. [ABSTRACT FROM AUTHOR]

The impact of sex on the prognosis of patients with esophageal cancer remains unclear. Evidence supports that sex- based disparities in esophageal cancer survival could be attributed to sex- specific risk exposures, such as age at diagnosis, race, socioeconomic status, smoking, drinking, and histological type. The aim of our study is to investigate the role of sex disparities in survival of patients who underwent surgery for esophageal cancer. A systematic review and meta-analysis of the existing literature in PubMed, EMBASE, and CENTRAL from December 1966 to February 2023, was held. Studies that reported sex-related differences in survival outcomes of patients who underwent esophagectomy for esophageal cancer were identified. A total of 314 studies were included in the quantitative analysis. Statistically significant results derived from 1-year and 2-year overall survival pooled analysis with Relative Risk (RR) 0.93 (95% Confidence Interval (CI): 0.90–0.97, I2 = 52.00) and 0.90 (95% CI: 0.85–0.95, I2 = 0.00), respectively (RR < 1 = favorable for men). In the postoperative complications analysis, statistically significant results concerned anastomotic leak and heart complications, RR: 1.08 (95% CI: 1.01–1.16) and 0.62 (95% CI: 0.52–0.75), respectively. Subgroup analysis was performed among studies with <200 and > 200 patients, histology types, study continent and publication year. Overall, sex tends to be an independent prognostic factor for esophageal carcinoma. However, unanimous results seem rather obscure when multivariable analysis and subgroup analysis occurred. More prospective studies and gender-specific protocols should be conducted to better understand the modifying role of sex in esophageal cancer prognosis. [ABSTRACT FROM AUTHOR]

Anastomotic leaks and stenoses remain critical complications in esophagectomy and are related to conduit perfusion. Surgical gastric preconditioning has been described but requires additional surgery and creates scar tissue, potentially hindering future operation. We sought to evaluate the feasibility and safety of percutaneous gastric preconditioning by angioembolization to improve perfusion of gastric conduits before esophagectomy in a high-risk patient cohort. Patients pending an esophagectomy for cancer and deemed to be high risk for anastomotic complications underwent preconditioning by image-guided angioembolization. Preconditioning was performed on an outpatient basis by means of superselective embolization of the left gastric and short gastric arteries. Intraoperative conduit perfusion evaluation with indocyanine green and postoperative surgical outcomes was reviewed. Seventeen patients underwent gastric preconditioning, with no complications observed. Thirteen of the 17 patients ultimately underwent esophagectomy; the remaining four patients were not candidates for an operation. Patients proceeded to surgery a median of 23 days (interquartile range, 21–27 days) after preconditioning. The intraoperative indocyanine green perfusion of all conduits was appropriate, with no tip demarcation and with a median time to dye uptake of 20s (interquartile range, 15–20s). There were no anastomotic stenoses or leaks noted within the series. Gastric conduit preconditioning by percutaneous angioembolization of the left gastric and short gastric arteries can be performed safely and without operative delay in high-risk patients. Further evaluation of preconditioning for conduit optimization is warranted to limit the critical complications of anastomotic leak and stenosis in esophagectomy. [ABSTRACT FROM AUTHOR]

Multidisciplinary team meetings (MDTs) are recommended for patients with esophageal cancer. Improved staging, timeliness to surgery and better adherence to guidelines have been attributed to MDTs, but there are few studies published on the MDTs' effect on survival. All patients with esophageal cancer in Sweden between 2006 and 2018 were grouped according to whether they had been discussed at an MDT as part of their clinical pathway. Factors affecting group allocation were explored with multivariable logistic regression, and the impact of MDT on survival was studied with Cox-regression and the Kaplan–Meier estimator. Of 6837 included patients, 1338 patients (20%) were not discussed at an MDT. Advanced age (80–90 years; odds ratio [OR] 0.25, 0.16–0.42 (95% confidence interval)) and clinical stage IVb (OR 0.65, 0.43–0.98) decreased the probability of being presented at an MDT, whereas high education level (OR 1.31, 1.02–1.67), being married (OR 1.20, 1.01–1.43), squamous histology (OR 1.50, 1.22–1.84) and later year of diagnosis (OR 1.33, 1.29–1.37 per year) increased the probability of an MDT. In multivariable adjusted analysis, MDT discussion was associated with improved survival (hazard ratios 0.72, 0.66–0.78) and median survival increased from 4.5 to 10.7 months. MDTs were associated with improved survival for esophageal cancer patients. Elderly patients with advanced disease and poor socioeconomic status were less likely to be presented at an MDT, but had clear survival-benefits if they were discussed in a multidisciplinary setting. [ABSTRACT FROM AUTHOR]

Posterior thoracic para-aortic lymph node (TPAN) metastasis is a distant metastasis of esophageal cancer. Several case reports have shown that radical esophagectomy and lymphadenectomy for posterior TPAN improve the prognosis of patients with cStage IVB esophageal cancer and solitary posterior TPAN metastasis; however, the true value of this procedure is unclear. The primary objective of this study was to evaluate the short- and long-term outcomes of lymphadenectomy for posterior TPAN after induction chemotherapy in esophageal cancer. This study enrolled 15 patients who underwent radical esophagectomy for cStage IVB esophageal cancer with solitary posterior TPAN metastasis after induction chemotherapy between January 2013 and October 2022 at our hospital. The short- and long-term of radical esophagectomy and lymphadenectomy for posterior TPAN were retrospectively evaluated. All patients who underwent radical esophagectomy and lymphadenectomy for posterior TPAN achieved a pR0 in this study. The median operative time and intraoperative blood loss were 385 minutes and 164 ml, respectively. Four patients (26.7%) had postoperative complications of Clavien-Dindo grade II or more. The median postoperative hospital stay was 15 days. The 5-year overall survival and recurrence-free survival rates were 55.6% (95% confidence interval: 23.1–79.0) and 55.0% (95% confidence interval: 25.3–77.2), respectively. We showed that lymphadenectomy for posterior TPAN metastasis was associated with an improved prognosis of some patients with advanced esophageal cancer. This technique may serve as a viable treatment option for patients who respond well to induction chemotherapy. [ABSTRACT FROM AUTHOR]

The standard treatment regimen for esophageal cancer is chemoradiation followed by esophagectomy. However, the use of neoadjuvant chemoradiotherapy damages the surrounding tissue, which potentially increases the risk of postoperative complications, including anastomotic leakage. The impact of definitive chemoradiotherapy (dCRT, 50.4 Gy radiotherapy) compared to the standard neoadjuvant scheme (nCRT, 41.4 Gy radiotherapy) prior to surgery on the incidence of anastomotic leakage remains poorly understood. To study this, all patients who received dCRT between 2011 and 2021 followed by esophagectomy were included. For each patient, two patients who received nCRT were selected as matched controls. Outcomes included postoperative anastomotic leakage, pulmonary and other complications, anastomotic stenosis, pulmonary and other postoperative complications (Clavien Dindo Classification ≥1), and overall survival. One hundred and eight patients were included with a median follow-up of 28 months. The time between neoadjuvant treatment and surgery was longer in the dCRT group compared to the nCRT group (65 vs. 48 days, P  < 0.001). Postoperatively, significantly more patients in the dCRT group suffered from anastomotic leakage (11% vs. 1%, P  = 0.04) and anastomotic stenosis (42% vs. 17%, P  < 0.01). No differences were found for other complications or overall survival between both groups. In conclusion, preoperative dCRT is associated with a higher risk of anastomotic leakage and stenosis. These complications, however, can be treated effectively. Therefore, esophagectomy after dCRT is considered to be an appropriate treatment strategy in a selected patient group. [ABSTRACT FROM AUTHOR]

The incidence of T4b esophageal cancer with aortic invasion but without distant metastasis is estimated to be between 3.8% and 4.6% of all esophageal cancer cases. Development of an aortoesophageal fistula in such cases is a rare but not unlikely event, leading to catastrophic consequences. The aim of this systematic review is to evaluate the importance of aortic stenting (Thoracic Endovascular Aortic Repair—TEVAR) and its optimal timing in the management of locally advanced esophageal cancer. A systematic literature search of the MEDLINE, Scopus, and Google Scholar databases was undertaken to identify relevant studies published up to March 2024. An individual patient data analysis was performed by forming a patient cohort with elective and salvage TEVAR subgroups, depending on the timing of the stenting. The study pool consisted of 25 studies incorporating 101 cases of locally advanced esophageal cancer, with a median age of 64 years (range 45–87 years). Of them, 50 patients underwent elective TEVAR compared with 51 patients receiving TEVAR in an acute salvage setting. Elective or prophylactic TEVAR was found to significantly increase esophageal resection rates (65.6% vs. 16.7% in the salvage subgroup, P  < 0.001), concurrently reducing complication rates (8.3% vs. 36.1%, P  < 0.001). Overall survival was also prolonged in the elective subgroup (8.3 vs. 4 months, P  = 0.001), with elective stenting being the only independent predictor of improved survival. In conclusion, management with aortic stenting in high-risk patients may reduce the catastrophic consequences of massive bleeding, minimize complications, and enhance survival rates. [ABSTRACT FROM AUTHOR]

Although esophageal cancers invading the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic resection (ER) are associated with a risk of lymph node metastasis, details of metastatic recurrence after additional treatment remain unknown. We aimed to identify the risk factors for metastatic recurrence and recurrence patterns in patients receiving additional treatment after ER for esophageal cancer. Between 2006 and 2017, patients with pT1a-MM/pT1b-SM esophageal cancer who underwent ER with additional treatment (esophagectomy, chemoradiotherapy [CRT], and radiation therapy) at 21 institutions in Japan were enrolled. We evaluated the risk factors for metastatic recurrence after ER with additional treatment. Subsequently, the rate and pattern (locoregional or distant) of metastatic recurrence were investigated for each additional treatment. Of the 220 patients who received additional treatment, 57, 125, and 38 underwent esophagectomy, CRT, and radiation therapy, respectively. In the multivariate analysis, lymphatic invasion was the sole risk factor for metastatic recurrence after additional treatment (hazard ratio, 3.50; P  = 0.029). Although the risk of metastatic recurrence with additional esophagectomy was similar to that with CRT (hazard ratio, 1.01; P  = 0.986), the rate of locoregional recurrence tended to be higher with additional esophagectomy (80.0% (4/5) vs. 36.4% (4/11)), leading to a better prognosis in patients with metastatic recurrence after additional esophagectomy than CRT (survival rate, 80.0% (4/5) vs. 9.1% (1/11)). Patients with lymphatic invasion have a high risk of metastatic recurrence after ER with additional treatment for pT1a-MM/pT1b-SM esophageal cancer. Additional esophagectomy may result in a better prognosis after metastatic recurrence. [ABSTRACT FROM AUTHOR]

Definitive chemoradiotherapy (DCRT) is administered as standard treatment for patients with cT4 and/or M1Lym esophageal squamous cell carcinoma (ESCC); however, its long-term result is inadequate. Although several studies have reported that conversion surgery can improve the survival of these patients, none have identified significantly better long-term survival than that achieved by DCRT. Thus, enhancing DCRT seems important to improve the survival of these patients. A strategy of shrinking tumor volume before DCRT and providing consolidation chemotherapy for systemic control is expected to improve the survival of these patients. Pembrolizumab plus cisplatin and fluorouracil has demonstrated good local control and significant improvement in the survival of patients with advanced esophageal cancer. Based on these results, the following strategy is proposed: This protocol should be applied as induction for these patients; then, DCRT should be provided depending on the initial response; and finally, adjuvant chemotherapy with an immune checkpoint inhibitor should be given to all responders. [ABSTRACT FROM AUTHOR]

Background: The real-world efficacy, prognostic factors, and adverse events of second-line nivolumab monotherapy and subsequent third-line therapy for unresectable or metastatic esophageal cancer have not been fully evaluated. Methods: This multi-institutional retrospective cohort study evaluated 184 consecutive patients treated with second-line nivolumab monotherapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, adverse events, long-term survival, and prognostic factors. Results: Among 128 patients with measurable lesions, the response rate was 23% and the disease control rate for all enrolled patients was 45%. The incidence of grade 3 or higher adverse events was 14%, but no treatment-related deaths presented. Median progression-free survival was 5.1 months and overall survival was 14 months, respectively. C-reactive protein level and performance status were identified as significant prognostic factors of overall survival through Cox proportional hazards analysis. The group with two favorable prognostic factors showed better overall survival than the groups with either one or zero prognostic factors (median overall survival: 22, 15, and 4.4 months, respectively). Among 69 patients who received third-line taxane anticancer agents, the progression-free survival was 6.7 months. Conclusions: Our study demonstrated that the real-world outcomes of second-line nivolumab monotherapy were comparable to those of previous randomized clinical trials in terms of tumor response, safety, and long-term survival. Furthermore, a good performance status and low C-reactive protein levels may identify patients who are likely to benefit from therapy. Third-line chemotherapy after nivolumab treatment may have an enhanced effect; however, further prospective studies are required to confirm this finding. [ABSTRACT FROM AUTHOR]

Purpose: Kinesiophobia refers to an irrational fear of physical activities or functional exercise due to the fear of pain or reinjury. Cancer patients who undergo esophagectomy are prone to developing kinesiophobia, which adversely affects their disease prognosis and quality of life. Somatic symptoms are closely related to kinesiophobia, but the mechanisms underlying this relationship remain unclear. Therefore, the current study aimed to explore the chain-mediation roles of intrusive rumination and avoidant coping in the relationship between somatic symptoms and kinesiophobia in cancer patients who underwent esophagectomy. Methods: A cross-sectional study was conducted in China from February 2023 to December 2023. A total of 279 postesophagectomy cancer patients were evaluated using the Symptom Check List 90 (SCL-90), Event Related Rumination Inventory (ERRI), Medical Coping Modes Questionnaire (MCMQ), and Tampa Scale of Kinesiophobia (TSK-11). Results: Kinesiophobia was significantly positively correlated with somatic symptoms, intrusive rumination, and avoidant coping (p < 0.001). Somatic symptoms had a direct association with kinesiophobia (β = 0.280, 95% CI (0.200, 0.360), p < 0.001). Furthermore, our model showed that somatic symptoms had a significant indirect association with kinesiophobia through the separate mediating effects of intrusive rumination (β = 0.204, 95% CI (0.145, 0.267), p < 0.001) and avoidant coping (β = 0.049, 95% CI (0.019, 0.088), p < 0.001), as well as through the chain-mediated effects of intrusive rumination-avoidant coping (β = 0.026, 95% CI (0.012, 0.044), p < 0.001). Conclusions: The findings of this study suggested that intrusive rumination and avoidant coping play separate and chain-mediated roles in the relationship between somatic symptoms and kinesiophobia in postesophagectomy cancer patients. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive drugs. However, the impact that the use of ACEI and ARB drugs will have on the survival of patients with hypertension and cancer is still unclear. Therefore, the present study aimed to investigate the effects of ACEI and ARB use on the survival of patients with cancer. The Embase, PubMed and Web of Science databases were used to systematically analyze the survival of hypertensive patients with cancer treated with ACEIs or ARBs. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ACEI and ARB use and patient survival. The relationship between the survival of patients with certain types of cancer and ACEI and ARB use was evaluated using the calculated HRs. Patients with ovarian, pancreatic, prostate, hepatocellular, lung, esophageal, gastric, colon, nasopharyngeal, head and neck tumors, gallbladder and rectal cancers that used ACEI and ARB analogs had significantly increased survival times, except for patients with breast cancer (HR, 1.04; 95% CI, 0.90-1.19; P<0.01) and uroepithelial carcinoma (HR, 1.15; 95% CI, 0.69-1.94; P<0.01), who had significantly decreased survival times, when compared with patients who did not use these drugs. Analysis of the relationship between the use of ACEIs or ARBs alone or in combination on the overall survival of hypertensive patients with cancer demonstrated that the use of ACEIs alone (HR, 1.00; 95% CI, 0.93-1.08; P<0.01) did not have a significant effect on the survival of these patients. By contrast, the survival time was increased in hypertensive patients with cancer who used either ARBs alone (HR, 0.89; 95% CI, 0.84-0.94; P<0.01) or a combination of ACEIs and ARBs (HR, 0.84; 95% CI, 0.78-0.91; P<0.01). The present meta-analysis demonstrated the potential effects of ACEI and ARB use on the overall survival of patients with cancer. Therefore, investigation of the underlying mechanisms of action of ACEIs and ARBs, as well as the identification of specific groups of patients who may benefit from these interventions, could potentially lead to novel therapeutic options and improve the prognosis of patients with cancer in the future. [ABSTRACT FROM AUTHOR]

Background: Genome instability (GI) is a hallmark of esophageal squamous cell carcinoma (ESCC) while factors affecting GI remain unclear. Methods: Here, we aimed to characterize genomic events representing specific mechanisms of GI based on 201 ESCC samples and validated our findings at the patient, single-cell and cancer cell-line levels, including a newly generated multi-omics dataset of the trial NCT04006041. Results: A two-gene (AHNAK and AHNAK2) mutation signature was identified to define the "AHNAK1/2-mutant" cancer subtype. Single-cell-assisted multi-omics analysis showed that this subtype had a higher neoantigen load, active antigen presentation, and proficient CD8 + T cell infiltrations, which were validated at pan-cancer levels. Mechanistically, AHNAK1/2-mutant ESCC was characterized by impaired response of TGF-β and the inefficient alternative end-join repair (Alt-EJ) that might promote GI. Knockdown of AHNAK in ESCC cell lines resulted in more Alt-EJ events and increased sensitivities to cisplatin. Furthermore, this two-gene signature accurately predicted better responses to DNA-damaging therapy in various clinical settings (HR ≈ 0.25). The two-gene signature predicted higher pCR rates in ESCCs receiving neoadjuvant immunotherapy-involved treatment. Finally, a molecular classification scheme was built and outperformed established molecular typing models in the prognosis stratification of ESCC patients. Conclusion: Our study extended our understanding of the AHNAK family in promoting GI and selecting treatment responders of ESCC. [ABSTRACT FROM AUTHOR]

Objective: To clarify the impact of the preoperative time intervals on short-term postoperative and pathologic outcomes in patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. Background: The impact of preoperative intervals on patients with esophageal cancer who received multimodality treatment remains unknown. Methods: Patients (cT1-4aN0-3M0) treated with nCRT plus esophagectomy were included using the Dutch national DUCA database. Multivariate logistic regression was used to determine the effect of different time intervals upon short-term postoperative and pathologic outcomes: diagnosis-to-nCRT intervals ( ≤5, 5--8, and 8--12 weeks), nCRT-to-surgery intervals (5--11, 11--17, and > 17 weeks) and total preoperative intervals ( ≤16, 16--25, and > 25 weeks). Results: Between 2010 and 2021, a total of 5052 patients were included. Compared with diagnosis-to-nCRT interval ≤5 weeks, the interval of 8 to 12 weeks was associated with a higher risk of overall complications (P=0.049). Compared with nCRT-to-surgery interval of 5 to 11 weeks, the longer intervals (11--17 and > 17 weeks) were associated with a higher risk of overall complications P= 0.016; P<0.001) and anastomotic leakage (P= 0.004; P=0.030), but the interval >17 weeks was associated with lower risk of ypN+ (P= 0.021). The longer total preoperative intervals were not associated with the risk of 30-day mortality and complications compared with the interval ≤ 16 weeks, but the longer total preoperative interval ( >25 weeks) was associated with higher ypT stage (P=0.010) and lower pathologic complete response rate (P= 0.013). Conclusions: In patients with esophageal cancer undergoing nCRT and esophagectomy, prolonged preoperative time intervals may lead to higher morbidity and disease progression, and the causal relationship requires further confirmation. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study is to assess the effectiveness of indocyanine-green (ICG)-guided lymphography (ICG-Lg) in reducing the incidence of chyle leak (CL) after esophagectomy. Background: Chylothorax may severely impact esophageal cancer surgery, and the pre-emptive ligation of the thoracic duct (TD) is the most widespread control of this complication. Intraoperative ICG-Lg has been recently embedded in minimally invasive esophagectomy to facilitate TD detection and pre-emptive ligation. Methods: This retrospective analysis included consecutive patients who underwent minimally invasive Ivor Lewis esophagectomy for cancer at a tertiary referral center between January 2018 and August 2023. Patients were routinely submitted to extended lymphadenectomy with TD ligation and removal. All patients treated after January 2021 underwent ICG-Lg for TD identification and ligation (ICG group) and compared with the previous series (no- ICG group). The primary outcome was the incidence of postoperative CL, while univariate and backward stepwise multivariate logistic regression models were performed to identify associated factors. Results: After including 320 patients, 151 (ICG group) were submitted to ICG-Lg before the pre-emptive TD ligation. Both groups presented similar characteristics, except for neoadjuvant therapy (P< 0.001) and preoperative comorbidities (P=0.045). Intraoperative ICG-Lg significantly reduced the incidence of postoperative CL (11.8% vs 4.6%, P=0.026) and was significantly associated with shorter median length of hospital stay (13 vs 9 d, P=0.006). However, CL after ICG-Lg was more likely to require repairing reoperation (P= 0.050). Conclusions: Intraoperative ICG-Lg demonstrated significantly lower rates of CL after total minimally invasive esophagectomy and, therefore, it should be routinely embedded in the standardized surgical technique of high-volume centers for esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Screening for Barrett's esophagus (BE) remains controversial, even for high-risk populations. Our study aimed to evaluate the proportion of patients diagnosed with esophageal adenocarcinoma (EAC) who were not screened for BE or did not receive recommended BE surveillance screening. We then evaluated the relationship between cancer staging and screening/surveillance opportunities. Methods: This single-center retrospective study included 187 patients from January 2016 to January 2022 with newly diagnosed EAC. Data extracted from patient charts included BE risk factors, and BE, endoscopic, and histologic history. Results: A total of 187 patients had a new diagnosis of EAC. Among this group, 44% had appropriate BE surveillance adherence, and 47% of patients met the criteria for BE screening but had not been screened prior to EAC diagnosis. Adherence to BE surveillance was associated with earlier stages of cancer on biopsy. No significant difference in cancer staging was found in those with missed BE screening opportunities. Discussion: Patients with a diagnosis of BE who adhered to surveillance guidelines had earlier stage EAC at diagnosis, which emphasizes the importance of surveillance. Most of those with an initial diagnosis of EAC had not received any BE screening. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is identified as a predominant health threat worldwide, with its highest incidence and mortality rates reported in China. The complex molecular mechanisms underlying EC, coupled with the differential incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) across various regions, highlight the necessity for in‐depth research targeting molecular pathogenesis and innovative treatment strategies. Despite recent progress in targeted therapy and immunotherapy, challenges such as drug resistance and the lack of effective biomarkers for patient selection persist, impeding the optimization of therapeutic outcomes. Our review delves into the molecular pathology of EC, emphasizing genetic and epigenetic alterations, aberrant signaling pathways, tumor microenvironment factors, and the mechanisms of metastasis and immune evasion. We further scrutinize the current landscape of targeted therapies, including the roles of EGFR, HER2, and VEGFR, alongside the transformative impact of ICIs. The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune‐mediated treatments, and introduces the burgeoning domain of antibody–drug conjugates, bispecific antibodies, and multitarget‐directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations. [ABSTRACT FROM AUTHOR]

In the last years, one-anastomosis gastric bypass (OAGB) has been proposed more frequently as obesity surgery technique. Several trials have demonstrated that the easier technical feasibility does not affect the long-term surgical result. However, concern about increased risk of gastric and esophageal cancers has been expressed by several bariatric surgeons. The present study reports the 2nd case of cancer of the gastrointestinal-jejunal anastomosis in a OAGB patient focusing the attention on some technical issues correlated and offering a systematic review of the literature. [ABSTRACT FROM AUTHOR]

FAM136A promotes the progression and metastasis of various tumors. However, there are few studies on the role of FAM136A in esophageal cancer (ESCA). The TCGA, GTEx, and GEO databases are employed to analyze the expression of FAM136A in ESCA, and qPCR and TMA experiments are performed for validation. Enrichment analyzes are performed to investigate the association of FAM136A expression with immune features, m6A modification, alternative splicing, cuproptosis, and the ceRNA network via bioinformatics analysis. FAM136A is highly expressed in ESCA and correlated with lymph node metastasis and overall survival (OS). Bioinformatics analysis suggested that FAM136A may participate in the following processes to promote ESCA development and progression: 1) Promotion of mast cells infiltration to influence the ESCA immune microenvironment, 2) HNRNPC upregulation to regulate m6A modification, 3) ALYREF upregulation to increase the occurrence of retained intron (RI) events, 4) CDK5RAP1 upregulation to achieve inhibition of tumor cell apoptosis, and 5) promotion of ESCA progression through the lncRNA SNHG15/hsa‐miR‐29c‐3p/FAM136A ceRNA network. FAM136A is a potential biomarker for ESCA diagnosis and treatment response evaluation, and the underlying mechanisms may be associated with immune infiltration, m6A modification, alternative splicing, cuproptosis, and the ceRNA regulatory network. [ABSTRACT FROM AUTHOR]

Background The incidence of esophageal and gastric carcinoma (GEC) in elderly patients is increasing, yet patients ≥75 years have historically been underrepresented in clinical trials. We sought to investigate palliative chemotherapy administration patterns and survival outcomes in older adults. Materials and Methods A retrospective analysis identified patients aged 65-74 (young-old) and ≥75 years (older-old) diagnosed with advanced GEC. Patient and tumor characteristics were recorded, with descriptive analysis, time-to-event data analysis using Kaplan-Meier curves and multivariate Cox proportional hazards regression analysis performed. Results One hundred and ninety-eight "young-old" and 109 'older-old' patients were identified. Patient characteristics were similar between groups except for Charlson Co-morbidity Index (CCI), with lower co-morbidities in the "young-old" compared to "older-old" cohort (P  < .001; CCI = 0 in 103 (52%) "young-old" vs 31 (28%) "older-old"). The primary diagnosis in both groups was adenocarcinoma. 119 (60%) "young-old" and 25 (23%) "older-old" patients received chemotherapy (P  < .001). Performance status was the primary explanation for chemotherapy non-receipt in both cohorts; age was the explanation in 21 (25%) "older-old" patients and none in the "young-old" patients. PFS for first-line systemic therapy in "young-old" patients was 6.4 (95% CI 5.9-7.6) versus 7.5 months (95% CI 5.1-11.3) in "older-old" patients (P  = .69) whilst respective OS was 12.3 (95% CI 10.1-15.5) and 10.4 months (95% CI 9.0-14.6) (P  = .0816). Toxicity prompted chemotherapy cessation in 17 (15%) "young-old" and 3 (13%) "older-old" patients (P  = .97). Multivariate analysis identified CCI and ECOG performance status as predictive for PFS and OS, respectively. No causative relationship was identified with other variables. Conclusion Our study of real-world older-adults show that significant number of "older-old" patients with GEC do not receive chemotherapy. Among "older-old" adults who do receive systemic therapy, outcomes are comparable; this underscores the importance of geriatric assessment-guided care and suggests that age alone should not be a barrier to receipt of chemotherapy in patients with advanced GEC. [ABSTRACT FROM AUTHOR]

Purpose The aim of the present study is to explore the possible association between periodontitis and upper gastrointestinal (UGI) cancers, including esophageal and gastric cancers, utilizing the Mendelian randomization method. Methods In this research, we utilized the Mendelian randomization method to examine the causal association between periodontitis and UGI cancers. Genome-wide association studies data for periodontitis were obtained from the Gene-Lifestyle Interactions in Dental Endpoints consortium, while UGI cancers' data were accessed from FinnGen's Biobank. After rigorously screening instrumental variables for periodontitis, we analyzed them with UGI cancers primarily using the inverse variance weighted. Finally, to identify outliers, the results were subjected to a leave-one-out sensitivity analysis. Results Inverse variance weighted (fixed effect) results revealed that periodontitis is a risk factor for gastric cancer (OR = 1.7735, 95% CI: 1.1576 to 2.7170, P  = 0.0085). As for esophageal cancer, no statistically significant correlation was observed. Furthermore, no outliers were detected in any of the results. Conclusion Our two-sample Mendelian randomization study obviously demonstrates a significant positive association between periodontitis and gastric cancer, while no statistically significant correlation was found for esophageal cancer. What is already known on this topic? Observational studies have indicated that patients with periodontitis have a higher overall incidence of cancer compared to individuals without periodontitis. However, traditional analytical methods have made it difficult to determine whether these associations are independent of confounding factors. Therefore, further evidence for causality may need to be obtained through a randomized trial, such as a Mendelian randomization (MR) analysis. What this study adds? Our two-sample MR (TSMR) study offers compelling genetic evidence, suggesting that periodontitis increases the risk of gastric cancer. How this study might affect research, practice, or policy? The results of this study have the potential to illuminate the relationship between periodontitis and gastric cancer, providing fresh insights into strategies for the prevention and management of this type of cancer. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is among the most aggressive malignancies, ranking as the seventh most prevalent malignant tumor worldwide. Lymph node metastasis (LNM) indicates localized spread of cancer and often correlates with a poorer prognosis, emphasizing the necessity for neoadjuvant systemic therapy before surgery. However, accurate identification of LNM in EC presents challenges due to the lack of satisfactory diagnostic techniques. Imaging techniques, including ultrasound and computerized tomography scans, have low sensitivity and accuracy in assessing LNM. Additionally, the existing serological detection lacks precise biomarkers. The intricate and not fully understood molecular processes involved in LNM of EC contribute to current detective limitations. Recent research has shown potential in using various molecules, circulating tumor cells (CTCs), and changes in the microbiota to identify LNM in individuals with EC. Through summarizing potential biomarkers associated with LNM in EC and organizing the underlying mechanisms involved, this review aims to provide insights that facilitate biomarker development, enhance our understanding of the underlying mechanisms, and ultimately address the diagnostic challenges of LNM in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Despite trimodality treatment, 10% to 20% of patients with esophageal cancer experience interval metastases after surgery. Restaging may identify patients who should not proceed to surgery, as well as a subgroup with limited metastases for whom long-term disease-control can be obtained. This study aimed to determine the proportion of patients with interval metastases after neoadjuvant chemoradiotherapy (nCRT) and to evaluate treatment and survival. Methods: Patients who had cT2-4aN0-3M0 esophageal cancer treated with nCRT were identified from a trial database. Metastases detected up to 14 weeks after nCRT on 18F-FDG-PET/CT or during surgery were categorized as oligometastases (≤3 lesions located in one single organ or one extra-regional lymph node station) or as non-oligometastases. The primary outcome was the proportion of patients with metastases after nCRT. The secondary outcomes were overall survival (OS) and the site and treatment of metastases. Results: Between 2013 and 2021, 973 patients received nCRT, and 10.3% had interval metastases. Of 100 patients, 30 (30%) had oligometastases, located mostly in non-regional lymph nodes (33.3%) or bones (26.7%). The median OS of this group was 13.8 months (95% confidence interval [CI] 9.2–27.1 months). Of 30 patients, 12 (40%) with oligometastases underwent potentially curative treatment, with a median OS of 22.8 months (95% CI 10.4–NA). The patients with non-oligometastases underwent mostly systemic therapy or BSC and had a median OS of 9 months (95% CI 7.4–10.9 months). Conclusions: Interval metastases were detected in about 10% of patients after nCRT, underscoring the importance of re-staging with 18F-FDG-PET/CT for those who proceed to surgery. A favorable survival might be accomplished for a subgroup of patients with oligometastases. [ABSTRACT FROM AUTHOR]

Background: Tumor-associated macrophages (TAM), a major component of the tumor microenvironment, play key roles in tumor formation and progression; however, mechanisms underlying TAM-induced tumor progression are complex and not well known. We previously reported that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) functions as a tumor promoter in some cancer contexts. Methods: We examined ANGPTL2 expression in paraffin-embedded tumor samples from resected specimens of 221 patients with esophageal cancer. Patients were subdivided into four groups based on immunohistochemistry scores described above: ANGPTL2-low/TAM-low, ANGPTL2-low/TAM-high, ANGPTL2-high/TAM-low, and ANGPTL2-high/TAM-high groups. Gene expression datasets of esophageal cancer cell lines were obtained from the cancer cell line encyclopedia public database. Results: In this study, we demonstrate that TAM infiltration is associated with poor prognosis in patients with esophageal cancer whose tumor cells show relatively higher ANGPTL2 expression levels; however, TAM infiltration did not affect prognosis in patients with ANGPTL2-low-expressing esophageal cancer, suggesting that ANGPTL2 expression in esophageal cancer cells is required for TAM-induced tumor progression. Our analysis of public datasets indicates a potential positive correlation of ANGPTL2 expression levels with that of transforming growth factor (TGF)-β, a TAM-activating factor, in esophageal cancer cell lines. Conclusion: We conclude that ANGPTL2 signaling in tumor cells supports TAM-induced tumor progression and contributes to poor prognosis in patients with esophageal cancer. These findings overall provide novel insight into pro-tumor ANGPTL2 functions and illustrate the essential role of cancer cell/TAM crosstalk in cancer progression. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer (EC) is a major health issue, ranking seventh in incidence and sixth in mortality worldwide. Despite advancements in multidisciplinary treatment approaches, the 5-year survival rate for EC remains low at 21%. Challenges in EC treatment arise from late-stage diagnosis, high malignancy, and poor prognosis. Understanding the tumor microenvironment is critical, as it includes various cellular and extracellular components that influence tumor behavior and treatment response. Mast cells (MCs), as tissue-resident immune cells, play dual roles in tumor dynamics. High-throughput single-cell RNA sequencing offers a powerful tool for analyzing tumor heterogeneity and immune interactions, although its application in EC is limited. Methods: In this study, we investigated the immune microenvironment of EC using single-cell RNA sequencing and established a comprehensive immune profile. We also performed analysis of upstream transcription factors and downstream pathway enrichment to further comprehensively decipher MCs in EC. Besides, we performed knockdown experiments to explore the role of epidermal growth factor receptor (EGFR) signaling pathway in MCs-tumor cell interactions, highlighting its potential as a prognostic marker. Finally, we constructed a prognostic model for EC, which provided valuable suggestions for the diagnosis and prognosis of EC. Results: Our analysis identified 11 major cell types, of which MCs were particularly present in pericarcinoma tissues. Further grouping of the 5,001 MCs identified 8 distinct subtypes, including SRSF7-highly expressed MCs, which showed strong tumor preference and potential tumor-promoting properties. Moreover, we identified the key signaling receptor EGFR and validated it by in vitro knockdown experiments, demonstrating its cancer-promoting effects. In addition, we established an independent prognostic indicator, SRSF7+ MCs risk score (SMRS), which showed a correlation between high SMRS group and poor prognosis. Conclusion: These findings illuminate the complex interactions within the tumor microenvironment of EC and suggest that targeting specific MCs subtypes, particularly via the EGFR signaling pathway, may present novel therapeutic strategies. This study establishes a comprehensive immune map of EC, offering insights for improved treatment approaches. [ABSTRACT FROM AUTHOR]