GNA14 and GNAQ somatic mutations cause spinal and intracranial extra-axial cavernous hemangiomas.

Extra-axial cavernous hemangiomas (ECHs) are complex vascular lesions mainly found in the spine and cavernous sinus. Their removal poses significant risk due to their vascularity and diffuse nature, and their genetic underpinnings remain incompletely understood. Our approach involved genetic analyses on 31 tissue samples of ECHs employing whole-exome sequencing and targeted deep sequencing. We explored downstream signaling pathways, gene expression changes, and resultant phenotypic shifts induced by these mutations, both in vitro and in vivo. In our cohort, 77.4% of samples had somatic missense variants in GNA14, GNAQ, or GJA4. Transcriptomic analysis highlighted significant pathway upregulation, with the GNAQ c.626A>G (p.Gln209Arg) mutation elevating PI3K-AKT-mTOR and angiogenesis-related pathways, while GNA14 c.614A>T (p.Gln205Leu) mutation led to MAPK and angiogenesis-related pathway upregulation. Using a mouse xenograft model, we observed enlarged vessels from these mutations. Additionally, we initiated rapamycin treatment in a 14-year-old individual harboring the GNAQ c.626A>G (p.Gln209Arg) variant, resulting in gradual regression of cutaneous cavernous hemangiomas and improved motor strength, with minimal side effects. Understanding these mutations and their pathways provides a foundation for developing therapies for ECHs resistant to current therapies. Indeed, the administration of rapamycin in an individual within this study highlights the promise of targeted treatments in treating these complex lesions.

Efficacy and Perioperative Safety of Robot-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer.

Background: Esophageal cancer (EC) remains a significant global health concern. Minimally invasive surgical techniques, including robot-assisted approaches, have emerged as promising options for improving outcomes and patient recovery in EC management. Objective: This study aims to evaluate the clinical utility of robot-assisted minimally invasive esophagectomy (RAMIE) in the treatment of EC. Methods: A total of 160 EC patients undergoing treatment at our hospital were included in this study. Patients were randomly assigned to either the research group, receiving RAMIE, or the control group, undergoing thoracoscopic minimally invasive esophagectomy (MIE). Surgical outcomes, postoperative recovery, complication rates, and changes in inflammatory factors (IFs) such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were compared between the two groups. Additionally, prognostic survival and EC recurrence rates were assessed at a 1-year follow-up. Results: The research group demonstrated longer operative times, a higher number of dissected lymph nodes, reduced intraoperative bleeding, and quicker postoperative recovery compared to the control group, with significantly fewer complications (P < .05). Furthermore, the research group exhibited lower levels of postoperative IFs and MDA, along with higher levels of SOD and GSH-Px, compared to the control group (P < .05). There was no significant difference between the two groups in terms of prognostic survival and EC recurrence rates (P > .05). Conclusion: RAMIE demonstrates superior efficacy in enhancing therapeutic outcomes and accelerating postoperative recovery in patients with EC, thus establishing its value in EC treatment protocols. RAMIE is suggested as a valuable therapeutic option and warrants clinical adoption for EC management.

High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis.

BACKGROUND: PTPRF interacting protein alpha 1 (PPFIA1) is reportedly related to the occurrence and progression of several kinds of malignancies. However, its role in esophageal squamous cell carcinoma (ESCC) is unclear. This current study investigated the prognostic significance and biological functions of PPFIA1 in ESCC. METHODS: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and Gene Expression Omnibus (GEO) were used to investigate PPFIA1 expression in esophageal cancer. The relationship between PPFIA1 expression and clinicopathological characteristics and patient survival was evaluated in GSE53625 dataset, and verified in the cDNA array based on qRT-PCR and tissue microarray (TMA) dataset based on immunohistochemistry. The impact of PPFIA1 on the migration and invasion of cancer cells were investigated by wound-healing and transwell assays, respectively. RESULTS: The expression of PPFIA1 was obviously increased in ESCC tissues versus adjacent esophageal tissues according to online database analyses (all P < 0.05). High PPFIA1 expression was closely related to several clinicopathological characteristics, including tumor location, histological grade, tumor invasion depth, lymph node metastasis, and tumor-node-metastasis (TNM) stage. High PPFIA1 expression was related to worse outcomes and was identified as an independent prognostic factor of overall survival in ESCC patients (GSE53625 dataset, P = 0.019; cDNA array dataset, P < 0.001; TMA dataset, P = 0.039). Downregulation of PPFIA1 expression can significantly reduce the migration and invasion ability of ESCC cells. CONCLUSION: PPFIA1 is related to the migration and invasion of ESCC cells, and can be used as a potential biomarker to evaluate the prognosis of ESCC patients.

CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF-1α.

C-X-C motif chemokine receptor 4 (CXCR4) belongs to the CXC chemokine receptor family, which mediates the metastasis of tumor cells and promotes the malignant development of cancers. However, its biological role and regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we found that CXCR4 expression was associated with lymph node metastasis and a poor prognosis. In vitro and in vivo studies demonstrated that CXCR4 overexpression promoted ESCC cell proliferation, migration, invasion, and survival, whereas silencing CXCR4 induced the opposite effects. Mechanically, HIF-1α transcriptionally regulates CXCR4 expression by binding to a hypoxia response element in its promoter. HIF-1α-induced ESCC cell migration and invasion were reversed by CXCR4 knockdown or treatment with MSX-122, a CXCR4 antagonist. Collectively, these data revealed that the HIF-1α/CXCR4 axis plays key roles in ESCC growth and metastasis and indicated CXCR4 as a potential target for ESCC treatment.

Comparison of clinicopathological features and prognostic significance between synchronous multiple primary and solitary esophageal squamous cell carcinomas.

BACKGROUND: Synchronous multiple primary esophageal squamous cell carcinoma (S-MPESCC) refers to more than one primary esophageal carcinoma detected in a solitary patient at the time of initial presentation. The purpose of this study was to evaluate the clinicopathological features, appropriate surgical approaches and long-term survival in patients with S-MPESCC by comparing with those with solitary esophageal squamous cell carcinoma (SESCC). METHODS: In total, 567 patients with esophageal squamous cell carcinoma surgically resected in Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2018 were screened for retrospective analysis (50 in the S-MPESCC group and 516 in the SESCC group). RESULTS: No significant difference was observed in terms of other characteristics except total alcohol consumption (P = 0.029). S-MPESCC had higher lymph node rate than SESCC (62.0% and 44.1%, respectively; P = 0.015) especially in upper mediastinal (32.0% and 18.6%, respectively; P = 0.023) and abdominal (38.0% and 22.8%, respectively; P = 0.017) regions. The survival was not different between the two groups, and the 5-year survival rates of S-MPESCC and SESCC were 46.2% and 50.8%, respectively (P = 0.507). But for patients with pT3-4 cancers, the survival in S-MPESCC was worse than that in SESCC (P = 0.033). In the multivariate analysis, pT stage of primary cancer was an important independent predictor of prognosis in patients with S-MPESCC (hazard ratio [HR], 3.968; 95% confidence interval [CI], 1.031 to 15.268; P = 0.045). CONCLUSIONS: S-MPESCC was significantly different from SESCC in terms of clinicopathological characteristics include alcohol intake and pattern of lymphatic metastasis. Furthermore, S-MPESCC showed worse long-term survival than SESCC with increasing depth of primary cancer infiltration.

High-mobility group AT-hook 2 promotes growth and metastasis and is regulated by miR-204-5p in oesophageal squamous cell carcinoma.

BACKGROUND: To investigate the expression of high-mobility group AT-hook 2 (HMGA2) and miR-204-5p in oesophageal squamous cell carcinoma (ESCC) and their biological roles in ESCC development and progression. METHODS: HMGA2 and miR-204-5p expression levels in ESCC tissues and cell lines were detected by qRT-PCR, Western blotting and immunohistochemical staining. ESCC cell lines were transfected with a small interfering RNA for HMGA2 and miR-204-5p mimic to downregulate and upregulate the expression levels of HMGA2 and miR-204-5p, respectively. The growth, migration and invasion abilities of ESCC cells were assessed by MTT, colony formation, wound-healing and Transwell assays, respectively. A luciferase reporter gene assay was used to determine whether the 3'-untranslated coding regions of HMGA2 could be directly bound by miR-204-5p. RESULTS: HMGA2 expression was markedly upregulated (P < .001), while miR-204-5p expression was markedly downregulated (P = .003) in ESCC tissues compared with adjacent normal tissues. HMGA2 expression was correlated with tumour size, invasion depth, lymph node metastasis and tumour-node-metastasis stage (all P < .05) and was identified as an independent prognostic factor for ESCC patients. The expression levels of HMGA2 and miR-204-5p were negatively correlated (r2  = 0.609, P < .001). HMGA2 knockdown or miR-204-5p overexpression markedly inhibited ESCC cell growth, migration and invasion (P < .05). In addition, restoration of HMGA2 expression partly reversed the inhibitory effects of miR-204-5p overexpression on migration and invasion (P < .05). The luciferase reporter gene assay suggested that HMGA2 is a direct downstream target of miR-204-5p. CONCLUSION: HMGA2 functions as an oncogene in the growth and metastasis of ESCC and is negatively regulated by miR-204-5p.

Comparative study of treatment options and construction nomograms to predict survival for early-stage esophageal cancer: a population-based study.

BACKGROUND: The aim of this study was to investigate the impact of several common treatment options on the long-term survival of patients with early-stage esophageal cancer and to construct nomograms for survival prediction. METHOD: This study was performed using the Surveillance, Epidemiology and End Results (SEER) database (2004-2015) on patients with early-stage (pT1N0M0) esophageal cancer who underwent endoscopic local therapy (ET), radiotherapy (RT), esophagectomy (ES) or neoadjuvant therapy (NT). Multivariate Cox regression was used to explore which factors influenced patient survival, and these factors were then incorporated into propensity sore matching (PSM) and the construction of nomogram plots. Kaplan-Meier analysis was used to compare whether there was a difference in long-term survival between the other three treatments and esophagectomy. RESULT: Data from 4184 patients were included in this study. Multivariate Cox regression analysis showed that age, grade, marital status, and treatment method were independent factors affecting survival. After matching, Kaplan-Meier analysis showed that the ET group had better CSS than the ES group, but no difference in OS, while the NT and RT groups had worse OS and CSS than the ES group. In the nomogram prediction model, the c-indexes of the training and validation cohorts were 0.805 and 0.794, respectively. Additionally the ROC curve (5-year AUC = 0.877) and DCA curve showed that the model had a good predictive effect. CONCLUSION: For early-stage esophageal cancer, the results of this study showed that ET is not inferior to ES. Based on the independent factors affecting prognosis identified in the study, we constructed and validated a predictive model for predicting long-term survival in patients with early-stage esophageal cancer.

The predictive value of a preoperative systemic immune-inflammation index and prognostic nutritional index in patients with esophageal squamous cell carcinoma.

Growing evidence indicates that systemic inflammation response and malnutrition status are correlated with survival in certain types of solid tumors. The aim of this study is to evaluate the association between the systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) and overall survival (OS) in patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. A consecutive series of 655 patients with resected ESCC who underwent esophagectomy were enrolled in the retrospective study. The preoperative SII was defined as platelet × neutrophil/lymphocyte counts. The PNI was calculated as albumin concentration (g/L) + 5 × total lymphocyte count (109 /L). The optimal cut-off values of SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and PNI were determined by receiver operating characteristic analysis. Survival analysis was performed using the Kaplan-Meier method with a log-rank test, followed by a multivariate Cox proportional hazards model. A high SII was significantly related to tumor size, histological type, invasion depth, and TNM stage (p < 0.05). A low PNI was significantly associated with age, tumor size, invasion depth, lymph node metastasis, and TNM stage (p < 0.05). Univariate analysis revealed that age, smoking history, tumor size, invasion depth, lymph node metastasis, SII, NLR, PLR, and PNI were predictors of OS (p < 0.05). Multivariate analysis identified age (p = 0.041), tumor size (p = 0.016), invasion depth (p < 0.001), lymph node metastasis (p < 0.001), SII (p = 0.033), and PNI (p = 0.022) as independent prognostic factors correlated with OS. There was a significant inverse relationship between the SII and PNI (r = 0.309; p < 0.001). The predictive value increased when the SII and PNI were considered in combination. Our results demonstrate that the preoperative high SII and low PNI are powerful indicators of aggressive biology and poor prognosis for patients with ESCC. The combination of SII and PNI can enhance the accuracy of prognosis.

Vav1 expression is increased in esophageal squamous cell carcinoma and indicates poor prognosis.

Recently, Vav1 has been suggested to play an essential role in the progression of human cancers. However, the correlation between Vav1 expression and prognosis of esophageal squamous cell carcinoma (ESCC) is still unknown. The aim of this study was to investigate Vav1 expression and its prognostic value in ESCC. The expression of Vav1 was detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting in ESCC tissues and matched nontumorous tissues. Immunohistochemistry (IHC) was carried out to detect Vav1 expression in paraffin samples from 112 primary ESCC patients. Survival analysis was performed using Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to evaluate the correlation of Vav1 expression with prognosis of ESCC patients. The expression levels of Vav1 mRNA and protein in ESCC tissues were both significantly higher than those in adjacent nontumorous tissues. High Vav1 expression was significantly correlated with larger tumor size (P = 0.015), depth of tumor invasion (P = 0.023), lymph node metastasis (P = 0.008) and TNM stage (P < 0.001). The rate of overall survival (OS) was significantly lower in patients with high Vav1 expression than those with low Vav1 expression (P = 0.014). Multivariate Cox analysis indicated that Vav1 expression is an independent prognostic factor for OS (HR = 1.660, 95%CI = 1.058-2.607, P = 0.028). In summary, our findings demonstrate that Vav1 may be a candidate molecular prognostic marker for patients with ESCC.

Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Esophageal Squamous Cell Carcinoma (ESCC) Cells.

BACKGROUND The aim of this study was to elucidate the role of Krüppel-Like factor 4 (KLF4) in cisplatin resistance in esophageal squamous cell carcinoma (ESCC) cells, which may eventually help to improve the treatment efficacy. MATERIAL AND METHODS Human esophageal squamous cell carcinoma (ESCC) cell line CaEs-17, TE-1, EC109, KYSE510, KYSE140, KYSE70, and KYSE30 were selected to detect their sensitivity to cisplatin. 5-Azacytidine-2'-deoxycytidine (5'-Aza-CdR) treatment and methylation-specific PCR (MS-PCR) were used to detect the methylation status for KLF4. Cell viability, apoptosis, and cell cycle were measured using methyl thiazolyl tetrazolium (MTT) assay, Annexin V affinity assay, and flow cytometry, respectively. RESULTS The sensitivity to cisplatin was different in the seven ESCC cell lines, with TE-1 having the lowest sensitivity and KYSE140 having the highest sensitivity. Interestingly, the level of KLF4 was relatively low in TE-1 cells; while it was high in KYSE140 cells. These results suggested that KLF4 may be involved in cisplatin resistance. The promoter region was mostly unmethylated in KYSE140 cells; while it was hypermethylated in TE-1 cells. After treatment with demethylation reagent 5-Aza-CdR, cisplatin sensitivities were significantly increased after upregulation of KLF4, as the IC50 values were significantly decreased in the TE-1 cell treated with 5-Aza-CdR. Furthermore, upregulation of KLF4 induced cell apoptosis and cell cycle arrest at S phase. CONCLUSIONS KLF4 enhances the sensitivity of cisplatin to ESCC cells through apoptosis induction and cell cycle arrest. Our data provided a novel insight to the mechanism of cisplatin resistance; overexpression of KLF4 may be a potential therapeutic strategy for cisplatin resistance in human ESCC.

[Expression of leptin and adiponectin in esophageal squamous cell carcinoma and their clinical significance].

OBJECTIVE: To preliminarily investigate the expression and clinical significance of leptin and adiponectin in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of leptin and adiponectin in ESCC and normal esophageal mucosal tissue was detected by immunohistochemical staining with tissue microarray. The correlation between leptin, adiponectin and clinicalpathological features was statistically analyzed. RESULTS: The expression of leptin was significantly upregulated in the ESCC than in the normal esophageal mucosa tissue [65.6% (80/122) versus 27.5% (11/40), P < 0.001]. Expression of leptin was significantly correlated with lymph node involvement and advanced tumor stage (P = 0.009 and P = 0.043, respectively). Expression of adiponectin was significantly down-regulated in ESCC compared with that in normal esophageal mucosal tissue [22.1% (27/122) versus 47.5% (19/40), P = 0.002]. Expression of adiponectin was significantly correlated with lymph node involvement (P = 0.020). Correlation analysis showed a positive correlation between the expression of leptin and lymph node metastasis and TNM stage (r = 0.235 and r = 0.183, respectively), and a negative correlation between the expression of adiponectin and lymph node metastasis (r = -0.229). There was no significant correlation between the expressions of leptin and adiponectin (P > 0.05), and between the body mass index and the expression of leptin and adiponectin, and lymph node metastasis (P > 0.05 for all). CONCLUSIONS: An imbalanced expression of adipocytokines exits in ESCC. The expression of leptin and adiponectin is correlated with lymph node metastasis and/or tumor stage. Therefore, imbalanced expression of leptin and adiponectin may have a potential role in the carcinogenesis and disease progression of ESCC.

[Effect of number of metastatic lymph nodes and metastatic lymph node ratio on the prognosis in patients with adenocarcinoma of the esophagogastric junction after curative resection].

OBJECTIVE: To analyze the effects of number of positive lymph nodes and metastatic lymph node ratio (LNR) in evaluation of recurrence risk and overall survival in patients with adenocarcinoma of the esophagogastric junction (AEG) after curative resection. METHODS: Clinical data of 337 AEG patients who underwent curative resection in our hospital were retrospectively reviewed. The pN stage was categorized based on the number of metastatic lymph nodes and LNR stage, and was determined by the best cutoff approach at log-rank test. Univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model were used to analyze the effects of pN and LNR on recurrence-free survival and overall survival of these patients. Receiver operating characteristic (ROC) curves were plotted to compare the accuracy of prognosis prediction with pN and LNR. RESULTS: The 5-year recurrence-free survival rate and overall survival rate for all patients were 25.5% and 29.9%, respectively. The 5-year recurrence-free survival rates were 47.6%, 23.2%, 17.1% and 5.7% for pN0, pN1, pN2, and pN3, respectively, (P < 0.001) and the 5-year overall survival rates were 53.3%, 28.9%, 18.9% and 7.3%, respectively (P < 0.001). The 5-year recurrence-free survival rates were 47.6%, 24.3%, 11.4% and 2.0% for LNR0, LNR1, LNR2, and LNR3, respectively (P < 0.001), and the 5-year overall survival rates were 53.3%, 28.5%, 15.0%, 2.6%, respectively (P < 0.001). Univariate analysis showed that tumor size, macroscopic type, degree of differentiation, pT, pN, LNR and TNM stage were significantly associated with RFS and OS (P < 0.05). Cox multivariate analysis showed that either pN or LNR was independent risk factor for RFS and OS (P < 0.001). When pN and LNR were entered into the Cox hazard ratio model as covariates at the same time, LNR remained as an independent prognosis factor for RFS and OS (P < 0.001), but pN was not (P > 0.05). ROC curves showed that the area under the curve of LNR stage was larger than that of pN stage in prediction of both RFS and OS, however the differences were not statistically significant (P > 0.05). CONCLUSIONS: LNR is an independent risk factor associated with the prognosis of AEG patients. The value of LNR in prediction of recurrence hazard and overall survival was better than that of pN stage. It offers some helpful suggestions for AEG patients risk classification, allowing clinicians to develop a reasonable treatment.

Early identification of severe immune checkpoint inhibitor associated myocarditis: From an electrocardiographic perspective.

OBJECTIVES: Immune checkpoint inhibitor (ICI)-associated myocarditis, particularly severe ICI-associated myocarditis, has a high mortality rate. However, the predictive value of electrocardiogram (ECG) remains unclear. The present study aimed to evaluate the predictive value of clinical and electrocardiographic parameters for severe myocarditis. METHODS: Clinical and electrocardiographic data of 73 cancer patients with ICI-associated myocarditis were retrospectively collected. The severity of ICI-associated myocarditis was graded using the NCCN guidelines for managing immunotherapy-related toxicities. Myocarditis grades 1-2 and grades 3-4 were classified as mild and severe myocarditis, respectively. Logistic regression analysis was performed to analyze the predictive value of each parameter in predicting severe myocarditis. RESULTS: Among the 73 patients with myocarditis, 20 (27.4%) patients had severe myocarditis. Compared with mild myocarditis group, sinus tachycardia (p = 0.001), QRS duration ≥110 ms (p = 0.001), prolonged QTc interval (p < 0.001), and bundle branch block (p = 0.007) at the time of myocarditis were more common in the severe myocarditis group. Logistic regression analysis revealed that sinus tachycardia (p = 0.028) and QTc interval prolongation (p = 0.007) were predictors of severe myocarditis. Whereas the predictive value of other electrocardiographic parameters was weak. Concurrent targeted therapy didn't increase the risk of severe myocarditis. A high NT-proBNP level was associated with severe myocarditis. CONCLUSIONS: ECG at the onset of myocarditis manifested as sinus tachycardia and prolonged QTc interval predicted a high risk of severe myocarditis. Early detection of ECG abnormalities may faciliate early detection of severe ICI-associated myocarditis.

Effect of Neoadjuvant Immunotherapy Combined with Chemotherapy on Pulmonary Function and Postoperative Pulmonary Complications in Esophageal Cancer: A Retrospective Study.

BACKGROUND: Neoadjuvant immunotherapy, targeting the PD-1 or PD-L1, combined with chemotherapy (NICT), can improve the radical resection and survival rates for locally advanced EC. However, it may impair pulmonary function, and the effect of NICT on pulmonary function and postoperative pulmonary complications in EC patients remains unknown. This study aimed to investigate whether NICT can affect pulmonary functions and postoperative pulmonary complications in EC patients. METHODS: The study retrospectively recruited 220 EC patients who received NICT at the Department of Esophageal Cancer in Tianjin Medical University Cancer Institute & Hospital from January 2021 to June 2022. Changes in pulmonary function before and after NICT were compared. Logistic regression analysis was performed to analyze the correlations of pulmonary functions and clinical characteristics with postoperative pulmonary complications, respectively. RESULTS: The FEV1% pred, FVC, FVC% pred, and FEV1/FVC% significantly increased after NICT, with a P-value of 0.018, 0.005, 0.001, and 0.036, respectively. In contrast, there was a significant decline in the DLCO (8.92 ± 2.34 L before NICT vs. 7.79 ± 2.30 L after NICT; P < 0.05) and DLCO% pred (102.97 ± 26.22% before NICT vs. 90.18 ± 25.04% after NICT; P < 0.05). High DLCO and DLCO% pred at baseline levels were risk factors for DLCO reduction in EC patients after NICT. Advanced age, smoking history, FEV1% pred after NICT, and FVC% pred baseline and after therapy were risk factors for postoperative pulmonary complications, with a P-value of 0.043, 0.038, 0.048, 0.034, and 0.004, respectively. Although the DLCO level decreased after NICT, it did not increase the incidence of postoperative pulmonary complications. CONCLUSION: NICT may improve pulmonary ventilation function but also lead to a decrease in DLCO and DLCO% pred in EC patients. Nevertheless, the decreased DLCO after NICT did not increase the risk of postoperative pulmonary complications.

Efficacy and complications of endoscopic thoracoscopic versus laparoscopic radical esophagectomy in esophageal cancer treatment: A retrospective study.

To evaluate the efficacy and postoperative complications of endoscopic thoracoscopic and laparoscopic radical esophagectomy compared to open surgery in esophageal cancer treatment. This retrospective study included 103 esophageal cancer patients admitted from August 2018 to March 2022, divided into observation (endoscopic surgery) and control (open surgery) groups. We compared intraoperative parameters, postoperative outcomes, immune function, and one-year overall survival (OS). Intraoperative bleeding volume, the retention time of chest tube, postoperative fasting time, and hospital stay in the observation group were smaller than those in the control group (P < .05). The differences were not statistically significant (P > .05) when comparing operative time, the number of intraoperative blood transfusion cases, and the rate of operating room extubation in these 2 groups. The differences were not statistically significant when comparing the amount of resected lymph nodes and the positive rate of incisal edge in these 2 groups (P > .05). There was no statistically significant difference in the complication rates such as pneumonia, pleural effusion, pneumothorax, pulmonary embolism, anastomotic fistula, the leakage of thoracic duct, the injury of RLN and arrhythmia in these 2 groups (P > .05). At 7 days postoperatively, the CD4+ and CD4+/CD8+ in the observation group and the control group were smaller than the preoperative ones in their same groups, and they were larger in the observation group than those in the control group (P < .05); There was no statistically significant difference on the CD8+ in the observation group and the control group at 7 days postoperatively compared with the preoperative ones in their same groups (P > .05). The 1-year postoperative OS rate was 81.63% (40/49) in the observation group and 72.22% (39/54) in the control group, and the difference was not statistically significant when comparing the OS rates of these 2 groups (P = .238, HR = 0.622, 95% CI = 0.279-1.385). Endoscopic thoracoscopic and laparoscopic esophagectomy offers less invasive treatment with significant short-term benefits and better preservation of immune function in esophageal cancer patients, making it a safe and effective surgical option.

A spatiotemporal comparative analysis on tumor immune microenvironment characteristics between neoadjuvant chemotherapy and preoperative immunotherapy for ESCC.

The average five-year survival rate for esophageal cancer, a common malignant tumor of the digestive system, is barely 20%. The majority of esophageal squamous cell carcinoma (ESCC) patients had already progressed to a locally advanced or even advanced stage at initial diagnosis, making routine surgery ineffective. Chemotherapy and immunotherapy are important neoadjuvant treatments for ESCC, however, it remains unknown how treatment will affect the immunological microenvironment, especially at the spatial level. Here, we presented the TME characters of ESCC from the temporal and spatial dimensions using scRNA-seq and ST, investigated the changes of immune cell clusters in the TME under neoadjuvant chemotherapy and preoperative immunotherapy, and explored the potential mechanisms. It was found that compared with chemotherapy, immunotherapy combined with chemotherapy increased the level of T cell proliferation, partially restored the function of exhausted T cells, induced the expansion of specific exhausted CD8 T cells, increased the production of dendritic cells (DCs), and supported the immune hot microenvironment of the tumor. We also found that CD52 and ID3 have potential as biomarkers of ESCC. Particularly, CD52 may be served as a predictor of the efficacy to screen the advantaged population of different regimens. Through multiple pathways, CAF2 and CAF5's antigen-presenting role affected the other fibroblast clusters, resulting in malignant transformation. We analyzed the immune microenvironment differences between the two regimens to provide a more thorough description of the ESCC microenvironment profile and serve as a foundation for customized neoadjuvant treatment of ESCC.

Extranodal metastasis is a powerful prognostic factor in patients with adenocarcinoma of the esophagogastric junction.

BACKGROUND AND OBJECTIVES: The purpose of this study is to estimate the effect of extranodal metastasis (EM) on recurrence and survival in patients with adenocarcinoma of the esophagogastric junction (AEG) after curative resection. METHODS: Clinical data from 284 node-positive AEG patients who underwent curative resection were reviewed. Univariate and multivariate analyses were conducted to elucidate the effect of EM on recurrence-free survival (RFS) and overall survival (OS). RESULTS: EM was detected in 70 (24.6%) of the 284 cases. It had a significant correlation with tumor size, Lauren type, histopathological grading, depth of tumor invasion, number of metastatic nodes, lymph node ratio, and TNM stage. The 5-year RFS and OS rates were 22.2% and 24.3%, respectively. Patients with EM had a significantly decreased RFS (16 vs. 36 months, P < 0.001) and OS (23 vs. 41 months, P < 0.001) compared with those without EM. Multivariate analyses identified EM as an independent prognostic factor (P = 0.003 and 0.001, respectively). CONCLUSION: The presence of EM increases recurrence probability and reduces OS probability of AEG patients with lymph node metastasis. EM is a powerful prognostic factor reflecting a particularly aggressive biological behavior. Better understanding of EM status can help clinicians with regard to treatment decision and prognosis evaluation.

[Risk factors of early recurrence and prognosis for patients with adenocarcinoma of gastroesophageal junction after curative resection].

OBJECTIVE: To investigate the risk factors for early recurrence of gastroesophageal junction adenocarcinoma (Siewert type II/III) after curative resection and the prognosis of these patients. METHODS: Retrospective analysis was performed for the 170 patients with recurrent AEG after curative resection in our hospital.Univariate and multivariate analysis were applied to investigate risk factors for early recurrence ( < 24 month), the prognosis of these patients were also analyzed. RESULTS: The rate of early recurrence of AEG after curative resection was 75.3%. Univariate analysis showed that tumor Borrmann type, invasive depth, lymph node metastasis, metastasis lymph node ratio (LNR) and TNM stage were significant factors associated with early recurrence after curative resection (P < 0.05). Multivariate analysis identified that only LNR and tumor invasive depth were independent risk factors for early recurrence (P < 0.05). The median disease free survival time (9, 20 months, P < 0.01), 5-year survival rate (2.4%, 12.6%, P < 0.01) and the median survival time after recurrence(5, 8 months, P = 0.004) between patients with high-LNR group and low-LNR group were significantly difference. CONCLUSIONS: LNR and tumor invasive depth were determined to be independent risk factors associate with early recurrence after curative resection for AEG. The patients with high-LNR have a poorer survival compared with those with low-LNR; For the patients with serosa invaded and high LNR should be closely followed up to detect recurrence and take effective treatment timely to improve patients outcomes.

[Analysis of the clinicopathologic characters and prognostic impact of extranodal metastasis in gastric cardia patients].

OBJECTIVE: To investigate the correlation between extranodal metastasis (EM) and clinicopathologic features as well as the effect of EM on the prognosis in gastric cardia patients. METHODS: Retrospective analysis was performed for the 323 cases with histologically proven adenocarcinoma of gastric cardia who underwent curative resection from January 2000 to January 2007. There were 272 male patients and 51 female patients with their median age of 63 (22 to 85) years. The relationship between clinicopathological features and extranodal metastasis was studied. The effects of the EM on the recurrence and survival of these patients were also analyzed. RESULTS: EM positive was detected in 67 (20.7%) of the 323 patients. The incidence of EM was correlated with tumor Lauren typing, differentiation degree, invasive depth and lymph node metastasis (χ(2) = 4.647-27.216, P < 0.05). The 5-year survival rate and media survival time between patients with EM and those without EM were 12.3%, 34.1% and 20, 39 months, there was a statistically significantly difference (χ(2) = 23.936, P = 0.000) in 5-year survival rate. Multivariate analysis identified that invasive depth, lymph node metustasis and EM as an independent prognostic factor of all the patients. To the last follow up, the cumulative probability of recurrence of EM-positive patients was significant higher than EM-negative patients (59.7% vs. 35.9%; χ(2) = 12.409, P = 0.000). To study furthermore, stratified analysis showed that, in the node-positive patients, the cumulative recurrence rate of EM-positive patients was higher than EM-negative patients (60.9% vs. 40.0%; χ(2) = 8.410, P = 0.004) and the 5-year survival rate of EM-positive patients was less than the EM-negative patients (12.9% vs. 30.1%; χ(2) = 12.939, P = 0.000), the differences were statistically significant. CONCLUSIONS: EM positive is determined to be an independent prognosis factor of gastric cardia after curative resection. EM-positive patients have a high risk for recurrence and a short time to live.

USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1.

Ubiquitin-specific protease 4 (USP4) represents a potential oncogene involved in various human cancers. Nevertheless, the biological roles and precise mechanism of USP4 in esophageal squamous cell carcinoma (ESCC) progression are not understood. Here, USP4 expression was found to be markedly upregulated in ESCC tumor tissues and cells. Loss- and gain-of-function assays suggested that USP4 silencing inhibited ESCC cell proliferation, migration, and invasion, while USP4 overexpression promoted these behaviors. Consistently, USP4 silencing repressed tumor growth and metastasis in an ESCC nude mouse model in vivo. As a target molecule of USP4, transforming growth factor-ß-activated kinase 1 (TAK1) also showed high expression in ESCC. Moreover, we observed that USP4 specifically interacted with TAK1 and stabilized TAK1 protein levels via deubiquitination in ESCC cells. Importantly, USP4 promotes ESCC proliferation, migration, and invasion via the MEK/ERK signaling pathway and can be inhibited by U0126. Neutral red (NR), an inhibitor of USP4 can suppress ESCC progression in vitro and in vivo. Overall, this study revealed that USP4/TAK1 plays crucial roles in ESCC progression by modulating proliferation, migration, and invasion, and USP4 might be a potential therapeutic target in ESCC.