Substitute or coexistence? mediastinoscopy-assisted versus thoracoscope-assisted esophagectomy in esophageal cancer - a meta-analysis of perioperative outcomes and long-term survival.

BACKGROUND: Currently, mediastinoscopy-assisted esophagectomy (MAE) and thoracoscope-assisted esophagectomy (TAE) represent two prevalent forms of minimally invasive esophagectomy extensively employed in the management of esophageal cancer (EC). The aim of this meta-analysis is to assess and compare these two surgical approaches concerning perioperative outcomes and long-term survival, offering valuable insights for refining surgical strategies and enhancing patient outcomes in this field. METHODS: Adhering to PRISMA guidelines, we systematically searched PubMed, Web of Science, Cochrane Library, Embase, and CNKI databases until March 1, 2024, for studies comparing MAE and TAE. Outcomes of interest included perioperative outcomes (intraoperative outcomes, postoperative recovery, postoperative complications) and survival rates. Statistical analyses were performed using RevMan 5.4, with heterogeneity dictating the use of fixed or random-effects models. RESULTS: Totally 21 relevant studies were finally included. MAE was associated with significantly shorter operation times ((MD=-59.58 min, 95% CI: -82.90, -36.26) and less intraoperative blood loss (MD=-68.34 mL, 95% CI: -130.45, -6.23). However, MAE resulted in fewer lymph nodes being dissected (MD=-3.50, 95% CI: -6.23, -0.78). Postoperative recovery was enhanced following MAE, as evidenced by reduced hospital stays and tube times. MAE significantly reduced pulmonary complications (OR=0.59, 95% CI: 0.44, 0.81) but increased the incidence of recurrent laryngeal nerve injury (OR=1.84, 95% CI: 1.30, 2.60). No significant differences were observed in anastomotic leakage, chylothorax, cardiac complications, wound infections, and gastric retention between MAE and TAE. The long-term survival outcomes showed no statistical difference (HR=1.05, 95% CI: 0.71-1.54). CONCLUSIONS: MAE offers advantages in reducing operation time, blood loss, and specific postoperative complications, particularly pulmonary complications, with a shorter recovery period compared to TAE. However, it poses a higher risk of recurrent laryngeal nerve injury and results in fewer lymph nodes being dissected. No difference in long-term survival was observed, indicating that both techniques have distinct benefits and limitations. These findings underscore the need for personalized surgical approaches in EC treatment, considering individual patient characteristics and tumor specifics.

A radiomics strategy based on CT intra-tumoral and peritumoral regions for preoperative prediction of neoadjuvant chemoradiotherapy for esophageal cancer.

OBJECTIVE: Develop a method for selecting esophageal cancer patients achieving pathological complete response with pre-neoadjuvant therapy chest-enhanced CT scans. METHODS: Two hundred and one patients from center 1 were enrolled, split into training and testing sets (7:3 ratio), with an external validation set of 30 patients from center 2. Radiomics features from intra-tumoral and peritumoral images were extracted and dimensionally reduced using Student's t-test and least absolute shrinkage and selection operator. Four machine learning classifiers were employed to build models, with the best-performing models selected based on accuracy and stability. ROC curves were utilized to determine the top prediction model, and its generalizability was evaluated on the external validation set. RESULTS: Among 16 models, the integrated-XGBoost and integrated-random forest models performed the best, with average ROC AUCs of 0.906 and 0.918, respectively, and RSDs of 6.26 and 6.89 in the training set. In the testing set, AUCs were 0.845 and 0.871, showing no significant difference in ROC curves. External validation set AUCs for integrated-XGBoost and integrated-random forest models were 0.650 and 0.749. CONCLUSION: Incorporating peritumoral radiomics features into the analysis enhances predictive performance for esophageal cancer patients undergoing neoadjuvant chemoradiotherapy, paving the way for improved treatment outcomes.

Increased resected lymph node stations improved survival of esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) and surgery have been recommended as the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC). In addition, nodal metastases decreased in frequency and changed in distribution after neoadjuvant therapy. This study aimed to examine the optimal strategy for lymph node dissection (LND) in patients with ESCC who underwent nCRT. METHODS: The hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were calculated using the Cox proportional hazard model. To determine the minimal number of LNDs (n-LNS) or least station of LNDs (e-LNS), the Chow test was used. RESULTS: In total, 333 patients were included. The estimated cut-off values for e-LNS and n-LNS were 9 and 15, respectively. A higher number of e-LNS was significantly associated with improved OS (HR: 0.90; 95% CI 0.84-0.97, P = 0.0075) and DFS (HR: 0.012; 95% CI: 0.84-0.98, P = 0.0074). The e-LNS was a significant prognostic factor in multivariate analyses. The local recurrence rate of 23.1% in high e-LNS is much lower than the results of low e-LNS (13.3%). Comparable morbidity was found in both the e-LNS and n-LND subgroups. CONCLUSION: This cohort study revealed an association between the extent of LND and overall survival, suggesting the therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, more lymph node stations being sampled leads to higher survival rates among patients who receive nCRT, and standard lymphadenectomy of at least 9 stations is strongly recommended.

Impact of deep muscle invasion on nodal status and survival in patients with pT2 esophageal squamous cancer.

BACKGROUND: Whether T2 esophageal squamous cell carcinoma should be subclassified remains controversial. We aimed to investigate the impact of the depth of muscularis propria invasion on nodal status and survival outcomes. METHODS: We identified patients with pT2 esophageal squamous cell carcinoma who underwent primary surgery from January 2009 to June 2017. Clinical data were extracted from prospectively maintained databases. Tumor muscularis propria invasion was stratified into superficial or deep. Binary logistic regression was used to determine risk factors for lymph node metastases. The impact of the depth of muscularis propria invasion on survival was investigated using Kaplan‒Meier analysis and a Cox proportional hazard regression model. RESULTS: A total of 750 patients from three institutes were investigated. The depth of muscularis propria invasion (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 2.46-6.35; p < 0.001) was correlated with lymph node metastases using logistic regression. T substage (hazard ratio [HR]: 1.37, 95% CI: 1.05-1.79; p < 0.001) and N status (HR: 1.51, 95% CI: 1.05-2.17; p < 0.001) were independent risk factors in multivariate Cox regression analysis. The deep muscle invasion was associated with worse overall survival (HR: 1.52, 95% CI: 1.19-1.94; p = 0.001) than superficial, specifically in T2N0 patients (HR: 1.38, 95% CI: 1.08-1.94; p = 0.035). CONCLUSIONS: We found that deep muscle invasion was associated with significantly worse outcomes and recommended the substaging of pT2 esophageal squamous cell carcinoma in routine pathological examination.

Mendelian randomization analysis of atopic dermatitis and esophageal cancer in East Asian and European populations.

Background: Emerging observational studies showed an association between atopic dermatitis (AD) and gastrointestinal cancers. However, it remains unclear whether this association is causal, particularly in the case of cancers like esophageal cancer, which exhibit ancestral genetic traits. Methods: To assess the potential causal relationship between AD and esophageal cancer across diverse ancestral backgrounds, we conducted a 2-sample Mendelian randomization study. Independent genetic instruments for AD from the FinnGen consortium (N case = 7024 and N control = 198 740), BioBank Japan (N case = 2385 and N control = 209 651) and Early Genetics and Lifecourse Epidemiology (EAGLE) eczema consortium (N case = 18 900 and N control = 84 166, without the 23andMe study) were used to investigate the association with esophageal cancer in the UK Biobank study (N case = 740 and N control = 372 016) and BioBank Japan esophageal cancer sample (N case = 1300 and N control = 197 045). Results: When esophageal cancer extracted from East Asian ancestry was used as a outcome factor, AD data extracted from BioBank Japan (OR = 0.90, 95% CI: 0.83-0.98), FinnGen consortium (OR = 0.86, 95% CI: 0.77-0.96), and EAGLE consortium (OR = 0.92, 95% CI: 0.81-1.06) were negatively associated with esophageal cancer susceptibility. However, AD as a whole did not show an association with esophageal cancer from European ancestry. Conclusion: This study provides support for a causal relationship between AD and esophageal cancer in East Asian populations but not between AD and esophageal cancer from European ancestry. The specific associations between esophageal cancer and AD appear to exhibit significant disparities between the East Asian and European regions.

Vitamin D receptor induces oxidative stress to promote esophageal squamous cell carcinoma proliferation via the p53 signaling pathway.

Background: Esophageal squamous cell carcinoma (ESCC) is a common pathological esophageal cancer with poor prognosis. Vitamin D deficiency reportedly occurs in ESCC patients, and this is related to single nucleotide polymorphism of vitamin D receptor (VDR). Objective: We investigated the effect of VDR on ESCC proliferation, invasion, and metastasis and its potential mechanism. Methods: ESCC and normal tissues were collected from 20 ESCC patients. The ESCC tissue microarray contained 116 pairs of ESCC and normal tissues and 73 single ESCC tissues. VDR expression and its clinicopathological role were determined by real-time quantitative polymerase chain reaction, Western blot, and immunohistochemistry staining. sh-VDR and VDR overexpression were used to validate the effect of VDR on ESCC cell phenotype, and tandem mass tag-based quantitative proteomics and bioinformatics methods identified differential VDR-related proteins. The downstream pathway and regulatory effect were analyzed using ingenuity pathway analysis (IPA). Differentially expressed proteins were verified through parallel reaction monitoring and Western blot. In vivo imaging visualized subcutaneous tumor growth following tail vein injection of VDR-deficient ESCC cells. Results: High VDR expression was observed in ESCC tissues and cells. Gender, T stage, and TNM stage were related to VDR expression, which was the independent prognostic factor related to ESCC. VDR downregulation repressed ESCC cell proliferation, invasion, and migration in vitro and subcutaneous tumor growth and lung metastases in vivo. The cell phenotype changes were reversed upon VDR upregulation, and differential proteins were mainly enriched in the p53 signaling pathway. TP53 cooperated with ABCG2, APOE, FTH1, GCLM, GPX1, HMOX1, JUN, PRDX5, and SOD2 and may activate apoptosis and inhibit oxidative stress, cell metastasis, and proliferation. TP53 was upregulated after VDR knockdown, and TP53 downregulation reversed VDR knockdown-induced cell phenotype changes. Conclusions: VDR may inhibit p53 signaling pathway activation and induce ESCC proliferation, invasion, and metastasis by activating oxidative stress.

Will synchronous esophageal and lung resection increase the incidence of anastomotic leaks? A multicenter retrospective study.

BACKGROUND: Reports on combined resection for synchronous lung lesions and esophageal cancer (CRLE) cases are rare and mostly individual cases. Furthermore, the feasibility of CRLE has always been a controversial topic. In the current study, the authors retrospectively analyzed the feasibility of CRLE and established an individualized prediction model for esophageal anastomotic leaks after CRLE by performing a multicenter retrospective study. METHODS: Patients who underwent esophagectomy between January 2009 and June 2021 were extracted from a four-center prospectively maintained database, and those with CRLE at the same setting were matched in a 1:2 propensity score-matched (PSM) ratio to esophagectomy alone (EA) patients. A nomogram was then established based on the variables involved in multivariate logistic regression analysis. Internal validation of the nomogram was conducted utilizing Bootstrap resampling. Decision and clinical impact curve analysis were computed to assess the practical clinical utility of the nomogram. A prognosis analysis for CRLE and EA patients by Kaplan-Meier curves was conducted. RESULTS: Of the 7152 esophagectomies, 216 cases of CRLE were eligible, and 1:2 ratio propensity score-matched EA patients were matched. The incidence of anastomotic leaks following CRLE increased significantly ( P =0.035). The results of the multivariate analysis indicated the leaks varied according to the type of lung resection (anatomic>wedge resection, P =0.016) and site of resected lobe (upper>middle/low lobe; P =0.027), and a nomogram was established to predict the occurrence of leaks accurately (area under the curve=0.786). Although no statistically significant difference in overall survival (OS) was observed in the CRLE group ( P =0.070), a trend toward lower survival rates was noted. Further analysis revealed that combined upper lobe anatomic resection was significantly associated with reduced OS ( P =0.027). CONCLUSION: Our study confirms that CRLE is feasible but comes with a significantly increased risk of anastomotic leaks and a concerning trend of reduced survival, particularly when upper lobe anatomic resections are performed. These findings highlight the need for careful patient selection and surgical planning when considering CRLE.

Deep Learning in Barrett's Esophagus Diagnosis: Current Status and Future Directions.

Barrett's esophagus (BE) represents a pre-malignant condition characterized by abnormal cellular proliferation in the distal esophagus. A timely and accurate diagnosis of BE is imperative to prevent its progression to esophageal adenocarcinoma, a malignancy associated with a significantly reduced survival rate. In this digital age, deep learning (DL) has emerged as a powerful tool for medical image analysis and diagnostic applications, showcasing vast potential across various medical disciplines. In this comprehensive review, we meticulously assess 33 primary studies employing varied DL techniques, predominantly featuring convolutional neural networks (CNNs), for the diagnosis and understanding of BE. Our primary focus revolves around evaluating the current applications of DL in BE diagnosis, encompassing tasks such as image segmentation and classification, as well as their potential impact and implications in real-world clinical settings. While the applications of DL in BE diagnosis exhibit promising results, they are not without challenges, such as dataset issues and the "black box" nature of models. We discuss these challenges in the concluding section. Essentially, while DL holds tremendous potential to revolutionize BE diagnosis, addressing these challenges is paramount to harnessing its full capacity and ensuring its widespread application in clinical practice.

The predictive value of a computed tomography-based radiomics model for the surgical separability of thymic epithelial tumors from the superior vena cava and the left innominate vein.

Background: The aim of this study was to develop a radiomics machine learning model based on computed tomography (CT) that can predict whether thymic epithelial tumors (TETs) can be separated from veins during surgery and to compare the accuracy of the radiomics model to that of radiologists. Methods: Patients who underwent thymectomy at our hospital from 2009 to 2017 were included in the screening process. After the selection of patients according to the inclusion and exclusion criteria, the cohort was randomly divided into training and testing groups, and CT images of these patients were collected. Subsequently, two-dimensional (2D) and three-dimensional (3D) regions of interest were labelled using ITK-SNAP 3.8.0 software, and Radiomics features were extracted using Python software (Python Software Foundation) and selected through the least absolute shrinkage and selection operator (LASSO) regression model. To construct the classifier, a support vector machine (SVM) was employed, and a nomogram was created using logistic regression to predict vascular inseparable TETs based on the radiomics score (radscore) and image features. To assess the accuracy of these models, area under receiver operating characteristic (ROC) curves of these models were calculated, and differences among the models were identified using the Delong test. Results: In this retrospective study, 204 patients with TETs were included, among whom 21 were diagnosed with surgical vascularly inseparable TETs. The area under ROC curve (AUC) of the 2D model, 3D model, 2D + 3D model, and radiologist diagnoses were 0.94, 0.92, 0.95, and 0.87 in the training cohort and 0.95, 0.92, 0.98, and 0.78 in testing cohort, respectively. The Delong test revealed a significant improvement in the performance of the radiomics models compared to radiologists' diagnoses. The logistic regression selected 3 image features, namely maximum diameter of the tumor, degree of abutment of vessel circumference >50%, and absence of the mediastinal fat layer or space between the tumor and surrounding structures. These features, along with the radscore, were included to develop a nomogram. The AUCs of this nomogram were 0.99 in both the training set and testing set, and the Delong test did not find a significant difference between ROC plots of the nomogram and radiomics models. Conclusions: The proposed radiomics model could accurately predict surgical vascularly inseparable TETs preoperatively and was shown to have a higher predictive value than the radiologists.

Causal relationship between lung diseases and risk of esophageal cancer: insights from Mendelian randomization.

BACKGROUND: An increasing number of cohort studies have indicated a correlation between lung diseases and esophageal cancer, but the exact causal relationship has not been definitively established. Therefore, the objective of this study is to assess the causal relationship between lung diseases and esophageal cancer. METHODS: Single-nucleotide polymorphisms (SNPs) related to lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF), along with outcomes data on esophageal cancer, were extracted from public genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) analysis was then performed using publicly available GWAS data to investigate the potential causal relationship. The effect estimates were primarily calculated using the fixed-effects inverse-variance-weighted method. RESULTS: Totally, 81 SNPs related to asthma among 218,792 participants in GWAS. Based on the primary causal effects model using MR analyses with the inverse variance weighted (IVW) method, asthma was demonstrated a significantly related to the risk of esophageal cancer (OR 1.0006; 95% CI 1.0003-1.0010, p = 0.001), while COPD (OR 1.0306; 95% CI 0.9504-1.1176, p = 0.466), lung cancer (OR 1.0003, 95% CI 0.9998-1.0008, p = 0.305), as well as IPF (OR 0.9999, 95% CI 0.9998-1.0000, p = 0.147), showed no significant correlation with esophageal cancer. CONCLUSIONS: The two-sample MR analysis conducted in this study revealed a positive causal relationship between asthma and esophageal cancer. In contrast, esophageal cancer demonstrated no significant correlation with COPD, lung cancer, or IPF. Further large-sample prospective studies are needed to validate these findings and to provide appropriate recommendations regarding esophageal cancer screening among patients with asthma.

MTHFD1L confers a poor prognosis and malignant phenotype in esophageal squamous cell carcinoma by activating the ERK5 signaling pathway.

MTHFD1L, a key enzyme of folate metabolism, is seldom reported in cancer. In this study, we investigate the role of MTHFD1L in the tumorigenicity of esophageal squamous cell carcinoma (ESCC). ESCC tissue microarrays (TMAs) containing 177 samples from 109 patients were utilized to evaluate whether MTHFD1L expression, determined using immunohistochemical analysis, is a prognostic indicator for ESCC patients. The function of MTHFD1L in the migration and invasion of ESCC cells was studied with wound healing, Transwell, and three-dimensional spheroid invasion assays in vitro and a lung metastasis mouse model in vivo. The mRNA microarrays and Ingenuity pathway analysis (IPA) were used to explore the downstream of MTHFD1L. Elevated expression of MTHFD1L in ESCC tissues was significantly associated with poor differentiation and prognosis. These phenotypic assays revealed that MTHFD1L significantly promote the viability and metastasis of ESCC cell in vivo and in vitro. Further detailed analyses of the molecular mechanism demonstrated that the ESCC progression driven by MTHFD1L was through up-regulation ERK5 signaling pathways. These findings reveal that MTHFD1L is positively associated with the aggressive phenotype of ESCC by activating ERK5 signaling pathways, suggesting that MTHFD1L is a new biomarker and a potential molecular therapeutic target for ESCC.

Integrated analysis reveals the microenvironment of non-small cell lung cancer and a macrophage-related prognostic model.

Background: In the treatment of non-small cell lung cancer (NSCLC), recent advances in immunotherapy have heralded a new era. Despite the success of immune therapy, a subset of patients persistently fails to respond. Therefore, to better improve the efficacy of immunotherapy and achieve the purpose of precision therapy, the research and exploration of tumor immunotherapy biomarkers have received much attention. Methods: Single-cell transcriptomic profiling was used to reveal tumor heterogeneity and the microenvironment in NSCLC. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was utilized to speculate the relative fractions of 22 infiltration immunocyte types in NSCLC. Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used for the construction of risk prognostic models and predictive nomograms of NSCLC. Spearman's correlation analysis was employed to explore the relationship between risk score and tumor mutation burden (TMB) and immune checkpoint inhibitors (ICIs). Screening of chemotherapeutic agents in the high- and low-risk groups was performed with the "pRRophetic" package in R. Intercellular communication analysis was conducted using the "CellChat" package. Results: We found that most tumor-infiltrating immune cells were T cells and monocytes. We also found that there was a significant difference in the tumor-infiltrating immune cells and ICIs across different molecular subtypes. Further analysis showed that M0 and M1 mononuclear macrophages were significantly different in different molecular subtypes. The risk prediction model was shown to have to ability to accurately predict the prognosis, immune cell infiltration, and chemotherapy efficacy of patients in the high and low-risk groups. Finally, we found that the carcinogenic effect of migration inhibitory factor (MIF) is mediated by binding to CD74, CXCR4, and CD44 receptors involved in MIF cell signaling. Conclusions: We have revealed the tumor microenvironment (TME) of NSCLC through single-cell data analysis and constructed a prognosis model of macrophage-related genes. These results could provide new therapeutic targets for NSCLC.

Identification of m6a-related signature genes in esophageal squamous cell carcinoma by machine learning method.

Background: We aimed to construct and validate the esophageal squamous cell carcinoma (ESCC)-related m6A regulators by means of machine leaning. Methods: We used ESCC RNA-seq data of 66 pairs of ESCC from West China Hospital of Sichuan University and the transcriptome data extracted from The Cancer Genome Atlas (TCGA)-ESCA database to find out the ESCC-related m6A regulators, during which, two machine learning approaches: RF (Random Forest) and SVM (Support Vector Machine) were employed to construct the model of ESCC-related m6A regulators. Calibration curves, clinical decision curves, and clinical impact curves (CIC) were used to evaluate the predictive ability and best-effort ability of the model. Finally, western blot and immunohistochemistry staining were used to assess the expression of prognostic ESCC-related m6A regulators. Results: 2 m6A regulators (YTHDF1 and HNRNPC) were found to be significantly increased in ESCC tissues after screening out through RF machine learning methods from our RNA-seq data and TCGA-ESCA database, respectively, and overlapping the results of the two clusters. A prognostic signature, consisting of YTHDF1 and HNRNPC, was constructed based on our RNA-seq data and validated on TCGA-ESCA database, which can serve as an independent prognostic predictor. Experimental validation including the western and immunohistochemistry staining were further successfully confirmed the results of bioinformatics analysis. Conclusion: We constructed prognostic ESCC-related m6A regulators and validated the model in clinical ESCC cohort as well as in ESCC tissues, which provides reasonable evidence and valuable resources for prognostic stratification and the study of potential targets for ESCC.

Safety and feasibility of a modularized procedure for trans-subxiphoid robotic extended thymectomy.

BACKGROUND: The purpose of this study was to introduce an "eight-step modularized procedure (M-RET)" for trans-subxiphoid robotic extended thymectomy for patients with myasthenia gravis (MG). Its safety and feasibility were further verified in this study. MATERIALS AND METHODS: This retrospective study included 87 consecutive MG patients who underwent trans-subxiphoid robotic extended thymectomy at our institution between September 2016 and August 2021. According to different resection models, patients were divided into two groups: traditional trans-subxiphoid robotic extended thymectomy group (T-RET group) and eight-step modularized technique group (M-RET group). Baseline demographic characteristics and operation-related parameters were collected and compared between the two groups. RESULTS: There were 41 (47.1%) patients in the M-RET group and 46 (52.9%) patients in the T-RET group. The M-RET group resected a greater amount of mediastinal adipose tissues and required more dissection time (median and interquartile range: 135.0, 125.0 to 164.0 v. 120.0, 105.0 to 153.8, P = 0.006) compared with the T-RET group. There were no statistically significant differences in terms of the intraoperative blood loss, duration of chest drainage, length of hospital stay, and postoperative complications between the two groups. There was no mortality or conversion in each of the two groups and all patients recovered well upon discharge. CONCLUSION: The eight-step modularized technique of trans-subxiphoid robotic extended thymectomy was verified to be a safe, effective, radical procedure, which offers unique superiority over ectopic thymic tissue resection.

The prognostic value of sarcopenia in oesophageal cancer: A systematic review and meta-analysis.

The loss of skeletal muscle mass and function is defined as sarcopenia, which might develop in elderly patients with cancers. It has been indicated as a potential negative factor in the survival of patients with malignant tumours. The aim of this systematic review and meta-analysis was to evaluate the associations between sarcopenia and survival outcomes or postoperative complications in patients with oesophageal cancer (EC). Web of Science, Embase, Medline, and Cochrane Library databases were searched until 10 May 2022, using keywords: sarcopenia, oesophageal cancer, and prognosis. Studies investigating the prognostic value of sarcopenia on EC survival were included. Forest plots and summary effect models were used to show the result of this meta-analysis. The quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS). A total of 1436 studies were identified from the initial search of four databases, and 41 studies were included for the final quantitative analysis. This meta-analysis revealed a significant association between sarcopenia and overall survival (OS) [hazard ratios (HR):1.68, 95% confidence interval (CI):1.54-1.83, P = 0.004, I2  = 41.7%] or disease-free survival (DFS) 1.97 (HR: 1.97, 95% CI: 1.44-2.69, P = 0.007, I2  = 61.9%) of EC patients. Subgroup analysis showed that sarcopenia remained a consistent negative predictor of survival when stratified by different treatment methods, populations, or sarcopenia measurements. Sarcopenia was also a risk factor for postoperative complications with a pooled odds ratio of 1.47 (95% CI: 1.21-1.77, P = 0.094, I2  = 32.7%). The NOS scores of all included studies were ≥6, and the quality of the evidence was relatively high. The results from the study suggested that sarcopenia was significantly associated with both survival outcomes and postoperative complications in EC patients. Sarcopenia should be appropriately diagnosed and treated for improving short-term and long-term outcomes of patients with EC.

Lymphovascular and Perineural Invasion After Neoadjuvant Therapy in Esophageal Squamous Carcinoma.

BACKGROUND: Lymphovascular invasion and perineural invasion are unfavorable prognostic factors in patients with esophageal squamous cell carcinoma. However, the prevalence and prognostic importance of lymphovascular invasion and perineural invasion after neoadjuvant chemoradiotherapy in these patients remains unclear. METHODS: We retrospectively reviewed specimens of 321 patients with pathologically diagnosed esophageal squamous cell carcinoma who underwent neoadjuvant chemoradiotherapy in our institution from 2017 to 2020. Lymphovascular invasion and perineural invasion were assessed by hematoxylin and eosin staining. Survival was analyzed using the log-rank test and multivariable Cox regression analysis. RESULTS: Lymphovascular invasion and perineural invasion were present in 12.5% (n = 40) and 17.8% (n = 57) of resection specimens, respectively. Lymphovascular invasion and perineural invasion were significantly more common in patients with advanced cancer (both P < .05). In the univariate analyses, lymphovascular invasion and perineural invasion were associated with shorter overall survival and disease-free survival. Multivariable analysis revealed that lymphovascular invasion after neoadjuvant therapy was an independent adverse prognostic factor for overall survival and disease-free survival. Subgroup analyses showed that lymphovascular invasion could identify cases with worse overall survival or disease-free survival among node-negative patients, indicating the role of lymphovascular invasion in the precise staging of pN0 patients. CONCLUSIONS: Lymphovascular invasion and perineural invasion were significantly negatively correlated with overall survival and disease-free survival. Lymphovascular invasion was an independent prognostic predictor in esophageal squamous cell carcinoma patients after neoadjuvant chemoradiotherapy. Lymphovascular invasion and perineural invasion should be considered in the histopathology workup for esophageal squamous cell carcinoma patients after neoadjuvant chemoradiotherapy.

The impact of geriatric nutritional risk index on esophageal squamous cell carcinoma patients with neoadjuvant therapy followed by esophagectomy.

Background: The Geriatric Nutritional Index (GNRI) has been indicated as a nutritional index which is highly associated with complications and mortality in older hospitalized patients. Moreover, early studies had suggested that GNRI is a potential prognostic indicator for some malignances. However, the prognostic value of GNRI in esophageal squamous cell carcinoma (ESCC) patients underwent neoadjuvant therapy followed by esophagectomy remains elusive. Materials and methods: This retrospective study incorporated 373 patients with ESCC who had underwent neoadjuvant therapy followed by radical esophagectomy at West China Hospital of Sichuan University between April 2011 and September 2021. The GNRI formula was: 1.489 × albumin (g/dl) + 41.7 × current weight/ideal weight. Patients were classified as GNRI-low (GNRI < 98.7) or GNRI high (GNRI ≥ 98.7). The association between GNRI and clinical survival status were assessed utilizing Kaplan-Meier methods and Cox regression analysis. Results: Three hundred and seventy three patients were retrospectively included in this study. 80 (21.5%) and 293 (78.5%) patients had been divided into the GNRI-low and GNRI-high groups respectively. Pathological T stage and the rate of nodal metastasis were significantly higher in the GNRI low group than in the GNRI high group (P = 0.003 and P = 0.001, respectively) among the examined demographic parameters. Furthermore, GNRI was significantly correlated with postoperative complications, patients with lower GNRI had a higher postoperative complication rate as compared with GNRI high group [Odds ratio: 2.023; 95% confidence interval (CI): 1.208-3.389; P = 0.007]. Univariate analysis of 5-year overall survival (OS) and disease-free survival (DFS) found that the rate of survival was considerably lower in the GNRI-low group than in the GNRI-high group (P < 0.001). However, multivariate analysis demonstrated that GNRI was not an independent risk factor. Conclusion: In patients with ESCC, low GNRI exhibited a poor nutritional indicator and related to postoperative complications after neoadjuvant therapy. Intensive follow-up after surgery should be performed for ESCC patients with low GNRI.

The prognostic impact of preoperative body mass index changes for patients with esophageal squamous cell carcinoma who underwent esophagectomy: A large-scale long-term follow-up cohort study.

Background: This study aims to investigate the relationship between preoperative body mass index changes (ΔBMI) and prognosis in patients with esophageal squamous cell carcinoma who underwent esophagectomy. Methods: We identified 1,883 patients with esophageal squamous cell carcinoma who underwent curative resection in our department between January 2005 and December 2013. Patients were grouped into a stable body mass index (ΔBMI = 0) group and a decreased body mass index (ΔBMI < 0) group. Risk factors for ΔBMI were assessed using logistic regression analysis. The impact of ΔBMI on survival was investigated using Kaplan-Meier curves and Cox regression. A nomogram for survival prediction was constructed and validated. Results: The results showed that T stage (OR: 1.30, 95% CI: 1.16-1.45, P < 0.001) and N stage (OR: 1.24, 95% CI: 1.11-1.38, P < 0.001) were independent risk factors for ΔBMI. The ΔBMI < 0 group had worse overall survival than the stable body mass index group (HR: 1.25, 95% CI: 1.08-1.44, P = 0.002). When stratified by stage, ΔBMI had the greatest prognostic impact in stage I tumors (HR: 1.82, 95%: 1.05-3.15, P = 0.033). In addition, multiple comparisons showed that decreasing ΔBMI correlated with worse prognosis. The ΔBMI-based nomogram presented good predictive ability with a C-index of 0.705. Conclusion: This study demonstrates that ΔBMI < 0 had an adverse impact on the long-term survival of patients with esophageal squamous cell carcinoma undergoing esophagectomy. These results may support further investigation of preoperative nutrition support.

Is Tumor Regression Grade Sufficient to Predict Survival in Esophageal Cancer with Trimodal Therapy?

BACKGROUND: This study aimed to assess the predictive value of tumor regression grade (TRG) and nodal status on survival in esophageal carcinoma with neoadjuvant chemoradiotherapy (nCRT). METHODS: Tumor pathologic regression and nodal status were assessed. Differences in survival stratified by TRG or nodal status were analyzed using the Kaplan-Meier method and log-rank test. The prognostic value of TRG and nodal status were analyzed using univariate and multivariate Cox proportional hazards methods. RESULTS: From July 2016 to June 2019, 253 patients with esophageal cancer underwent nCRT followed by surgery. Significant differences were presented in survival according to nodal status but not TRG. Multivariate analysis showed that nodal status and not TRG was the only independent predicter for overall survival (HR: 3.550, 95% CI: 2.264-5.566, P < 0.001) and disease-free survival (HR: 2.801, 95% CI: 1.874-4.187, P < 0.001). The modified TRG system combining tumor regression with nodal status stratified patients survival with good discrimination. CONCLUSIONS: Lymph node status impacts more importantly than TRG on survival for patients with esophageal cancer undergoing nCRT plus esophagectomy. The modified TRG system may facilitate postoperative treatment decisions and survival surveillance.