crossing96/oncoscreening huggingface dataset:
Video-assisted mediastinoscopic and laparoscopic transhiatal esophagectomy for esophageal cancer.	BACKGROUND: Mediastinoscopy was originally applied for lymph node biopsy and mediastinal tumor resection. Improved video imaging with spreadable working channels enabled mediastinoscopy for inspection and tissue biopsy in the superior mediastinum but it is rarely used in minimally invasive esophageal cancer surgery. In this prospective trial, the practicability and security of spreadable video-assisted mediastinoscopic combined with laparoscopic transhiatal esophagectomy (VAME) with video-assisted thoracoscopic esophagectomy (VATE) were compared. METHODS: A total of 200 eligible patients with esophageal squamous cell carcinoma were randomly divided into VAME or VATE groups. Early postoperative outcomes and lymph node dissection between the two groups were compared. RESULTS: The operation time was significantly shorter (164.3 ± 47.0 min vs. 265.4 ± 47.2 min, P < 0.001), the number of dissected lymph nodes was less (15.8 ± 4.5 vs. 20.3 ± 6.5, P < 0.001), and the intraoperative blood loss was also significantly reduced (94.7 ± 56.7 mL vs. 184.4 ± 65.2 mL, P < 0.001) in the VAME compared to the VATE group, respectively. The incidence of pneumonia was lower (7% vs. 29%; P < 0.001) and the length of hospital stay was shorter in the VAME group compared to the VATE group (18.0 ± 7.6 days vs. 23.2 ± 7.2, P < 0.001, respectively). The chyle leak incidence appeared to be lower in the VAME group but statistical significance was not reached (1% vs. 4%; P = 0.369). There were no differences in the incidence of anastomotic leakages and recurrent laryngeal nerve paralysis between the groups. No 30-day mortality occurred in any of the cases. CONCLUSION: VAME appears to be a practicable and secure method for esophagectomy but needs further proof of concept. CLINICAL REGISTRATION NUMBER: Registered at Chinese Clinical Trial Registry, ChiCTR1900022797.	esophagus
Inhibition of Wnt/β-Catenin Signaling Sensitizes Esophageal Cancer Cells to Chemoradiotherapy.	The standard treatment of locally advanced esophageal cancer comprises multimodal treatment concepts including preoperative chemoradiotherapy (CRT) followed by radical surgical resection. However, despite intensified treatment approaches, 5-year survival rates are still low. Therefore, new strategies are required to overcome treatment resistance, and to improve patients' outcome. In this study, we investigated the impact of Wnt/β-catenin signaling on CRT resistance in esophageal cancer cells. Experiments were conducted in adenocarcinoma and squamous cell carcinoma cell lines with varying expression levels of Wnt proteins and Wnt/β-catenin signaling activities. To investigate the effect of Wnt/β-catenin signaling on CRT responsiveness, we genetically or pharmacologically inhibited Wnt/β-catenin signaling. Our experiments revealed that inhibition of Wnt/β-catenin signaling sensitizes cell lines with robust pathway activity to CRT. In conclusion, Wnt/β-catenin activity may guide precision therapies in esophageal carcinoma patients.	esophagus
Immunotherapy in esophagogastric cancer.	The uses of immune checkpoint inhibitors have now been advanced to include the first-line treatment of esophagogastric cancers. Initially approved for the treatment of chemotherapy-refractory programmed death ligand 1-positive or microsatellite instability (MSI)-high esophagogastric adenocarcinoma, these agents have been shown in earlier-line trials to have an additive benefit with first-line chemotherapy, and superiority to chemotherapy, in MSI-high cancers. Pembrolizumab and nivolumab have received approval for the second-line treatment of esophageal squamous cancer. The addition of nivolumab to first-line chemotherapy in gastric and gastroesophageal junction (GEJ) adenocarcinoma improved survival, progression-free survival, and response, findings that led to regulatory approval. The addition of pembrolizumab to first-line chemotherapy in esophageal and GEJ adenocarcinoma and squamous cancer also improved all outcomes, which led to the approval of pembrolizumab as part of first-line chemotherapy. The addition of pembrolizumab to first-line chemotherapy in human epidermal growth factor receptor 2-positive esophagogastric adenocarcinoma was also recently approved. In addition, the adjuvant use of nivolumab was recently approved in esophageal and GEJ cancer after chemoradiotherapy and surgery in patients with residual disease found at surgery. This article reviews recent advances in the use of immune checkpoint inhibitor therapy in esophagogastric cancers.	esophagus
Clinical Significance of [(18)F] Fluoro-2-Deoxy-d-Glucose/Computed Tomographic Avid Hilar Lymph Nodes in Esophageal Carcinoma Patients.	BACKGROUND: The assumption that increased [(18)F] fluoro-2-deoxy-d-glucose (FDG) uptake in hilar nodes on positron emission tomography/computed tomography (PET/CT) imaging is indicative of distant metastasis can result in palliative rather than curative care in patients with esophageal cancer. This study aimed to determine the significance of increased FDG uptake in hilar nodes in patients with potentially curable, locally advanced disease at initial staging. METHODS: We included patients with biopsy specimen-proven esophageal carcinoma who had pretreatment FDG-PET/CT at initial staging and follow-up imaging >1 year. We excluded patients with distant hematogeneous metastases. Hilar nodes were considered concerning for metastatic disease when the maximum standardized uptake value was >2.5 or FDG uptake was visually greater than the mediastinal background. RESULTS: We reviewed FDG-PET CT scans from 806 patients treated for esophageal cancer from 2010 to 2018 and identified 42 patients with FDG-avid hilar adenopathy. Thirteen patients underwent histologic assessment, and 29 were monitored with imaging. None of the 42 patients had distant metastatic disease on the initial workup, and all were treated curatively. In follow-up, 2 of 42 patients eventually manifested hilar nodal metastases after treatment; 1 who had a biopsy specimen-negative hilar node at initial staging and another who did not have a biopsy of the hilar node. CONCLUSIONS: Increased FDG uptake in hilar nodes in patients with localized esophageal cancer was not indicative of nonregional nodal metastasis. Patients in these situations should be approached with curative intent. The need for biopsy of FDG-avid hilar nodes in this cohort should be carefully considered due to the low diagnostic utility.	esophagus
Presence of serum RalA and serum p53 autoantibodies in 1833 patients with various types of cancers.	BACKGROUND: RalA is a member of the Ras superfamily of small GTPases. The Anti-RalA autoantibodies (s-RalA-Abs) act as tumor markers in various types of cancer and are negatively associated with the p53 autoantibodies (s-p53-Abs). This study aimed to evaluate the relationship between s-RalA-Abs and s-p53-Abs in various types of cancer. METHODS: A total of 1833 cancer patients (esophageal cancer, 172; hepatocellular carcinoma, 91; lung cancer, 269; gastric cancer, 317; colon cancer, 262; breast cancer, 364; and prostate cancer, 358) and 73 healthy subjects were enrolled in the study. The levels of s-RalA-Abs and s-p53-Abs were analyzed using enzyme-linked immunosorbent assay, and the positivity rates and relations between the two autoantibodies were evaluated. The cutoff values for s-RalA abs and s-p53 abs were set as mean + 2 standard deviation and the values higher than the cutoff values were defined as positive. RESULTS: The titers in all cancer types were significantly higher than those in the controls (P < 0.01). The positivity rates for s-RalA-Abs ranged between 11.7 and 21.5%, and those for s-p53-Abs ranged between 12 and 28.5%. A combined assay of the two antibodies revealed positivity rates of 20.9 and 44.2%. In Stage 0/I/II tumors, the positivity rates of the combination of the two antibodies ranged between 21.5 and 42.3%. The two autoantibodies were complementary to each other in the prostate and breast cancers, but independent in other carcinomas. CONCLUSION: The combined use of s-RalA-Abs and s-p53-Abs tended to increase the positivity rate in all cancers, including Stage 0/I/II cancers.	esophagus
Impact of radiogenomics in esophageal cancer on clinical outcomes: A pilot study.	BACKGROUND: Esophageal cancer (ESCA) is the sixth most common malignancy in the world, and its incidence is rapidly increasing. Recently, several microRNAs (miRNAs) and messenger RNA (mRNA) targets were evaluated as potential biomarkers and regulators of epigenetic mechanisms involved in early diagnosis. In addition, computed tomography (CT) radiomic studies on ESCA improved the early stage identification and the prediction of response to treatment. Radiogenomics provides clinically useful prognostic predictions by linking molecular characteristics such as gene mutations and gene expression patterns of malignant tumors with medical images and could provide more opportunities in the management of patients with ESCA. AIM: To explore the combination of CT radiomic features and molecular targets associated with clinical outcomes for characterization of ESCA patients. METHODS: Of 15 patients with diagnosed ESCA were included in this study and their CT imaging and transcriptomic data were extracted from The Cancer Imaging Archive and gene expression data from The Cancer Genome Atlas, respectively. Cancer stage, history of significant alcohol consumption and body mass index (BMI) were considered as clinical outcomes. Radiomic analysis was performed on CT images acquired after injection of contrast medium. In total, 1302 radiomics features were extracted from three-dimensional regions of interest by using PyRadiomics. Feature selection was performed using a correlation filter based on Spearman's correlation (ρ) and Wilcoxon-rank sum test respect to clinical outcomes. Radiogenomic analysis involved ρ analysis between radiomic features associated with clinical outcomes and transcriptomic signatures consisting of eight N6-methyladenosine RNA methylation regulators and five up-regulated miRNA. The significance level was set at P < 0.05. RESULTS: Of 25, five and 29 radiomic features survived after feature selection, considering stage, alcohol history and BMI as clinical outcomes, respectively. Radiogenomic analysis with stage as clinical outcome revealed that six of the eight mRNA regulators and two of the five up-regulated miRNA were significantly correlated with ten and three of the 25 selected radiomic features, respectively (-0.61 < ρ < -0.60 and 0.53 < ρ < 0.69, P < 0.05). Assuming alcohol history as clinical outcome, no correlation was found between the five selected radiomic features and mRNA regulators, while a significant correlation was found between one radiomic feature and three up-regulated miRNAs (ρ = -0.56, ρ = -0.64 and ρ = 0.61, P < 0.05). Radiogenomic analysis with BMI as clinical outcome revealed that four mRNA regulators and one up-regulated miRNA were significantly correlated with 10 and two radiomic features, respectively (-0.67 < ρ < -0.54 and 0.53 < ρ < 0.71, P < 0.05). CONCLUSION: Our study revealed interesting relationships between the expression of eight N6-methyladenosine RNA regulators, as well as five up-regulated miRNAs, and CT radiomic features associated with clinical outcomes of ESCA patients.	esophagus
Incidence and Mortality in Upper Gastrointestinal Cancer After Negative Endoscopy for Gastroesophageal Reflux Disease.	BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what extent a negative upper endoscopy in patients with GERD is associated with decreased incidence and mortality in upper gastrointestinal cancer (ie, esophageal, gastric, or duodenal cancer). METHODS: We conducted a population-based cohort study of all patients with newly diagnosed GERD between July 1, 1979 and December 31, 2018 in Denmark, Finland, Norway, and Sweden. The exposure, negative upper endoscopy, was examined as a time-varying exposure, where participants contributed unexposed person-time from GERD diagnosis until screened and exposed person-time from the negative upper endoscopy. The incidence and mortality in upper gastrointestinal cancer were assessed using parametric flexible models, providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among 1,062,740 patients with GERD (median age 58 years; 52% were women) followed for a mean of 7.0 person-years, 5324 (0.5%) developed upper gastrointestinal cancer and 4465 (0.4%) died from such cancer. Patients who had a negative upper endoscopy had a 55% decreased risk of upper gastrointestinal cancer compared with those who did not undergo endoscopy (HR, 0.45; 95% CI, 0.43-0.48), a decrease that was more pronounced during more recent years (HR, 0.34; 95% CI, 0.30-0.38 from 2008 onward), and was otherwise stable across sex and age groups. The corresponding reduction in upper gastrointestinal mortality among patients with upper endoscopy was 61% (adjusted HR, 0.39; 95% CI, 0.37-0.42). The risk reduction after a negative upper endoscopy in incidence and mortality lasted for 5 and at least 10 years, respectively. CONCLUSIONS: Negative upper endoscopy is associated with strong and long-lasting decreases in incidence and mortality in upper gastrointestinal cancer in patients with GERD.	esophagus
[Methylation status of DACH1 gene in esophageal cancer and its clinical significance].	OBJECTIVE: To analyze the correlation of methylation status of dachshund homolog 1 (DACH1) gene in tumor tissues with clinicopathological characteristics and prognosis of patients of esophageal cancer. METHODS: Tumor tissue, paracancerous tissue and normal esophageal mucosal specimens of 104 patients with esophageal cancer were collected. Methylation-specific PCR was used to determine the methylation status of the DACH1 gene. Univariate analysis and multivariate Logistic regression model were used to analyze the correlation between DACH1 methylation status and clinical pathological characteristics of the patients. Kaplan-Meier survival curve was used to analyze the relationship between DACH1 methylation status and prognostic survival of patients. RESULTS: The methylation rate of the DACH1 gene in esophageal cancer tumor tissue was 30.77% (32/104), which was higher than those in adjacent tissues (1.92%) and normal esophageal mucosa (0%) (P< 0.05). The methylation status of the DACH1gene in tumor tissues of patients did not correlate with the patient's age, gender, and pathological type (P> 0.05) but tumor differentiation, TNM staging, and lymph node metastasis(P< 0.05). The degree of tumor differentiation, TNM stage, and lymph node metastasis of patients are independent risk factors for the methylation status of the DACH1 gene. By March 2020, 89 of the 104 patients had died. Among them, the median survival foresophageal cancer patients with DACH1 gene methylation was 22 months, which was lower than 34 months of those without DACH1 methylation (P< 0.05). CONCLUSION: Methylation of the DACH1 gene may be involved in the occurrence and progress of esophageal cancer. The degree of tumor differentiation, TNM stage, and lymph node metastasis of patients are independent risk factors for the methylation status of the DACH1 gene. Patients with esophageal cancer but unmethylated DACH1 gene have a longer prognostic survival.	esophagus
Increased coexpression of PD-L1 and TIM3/TIGIT is associated with poor overall survival of patients with esophageal squamous cell carcinoma.	BACKGROUND: Immune checkpoint (IC) blockades (ICBs) significantly improve patients' clinical outcomes with solid tumors. Because the objective response rate of single-agent ICB is limited, it is meaningful to explore the combination of ICs for immunotherapy. METHODS: RNA sequencing data of 95 newly diagnosed patients with esophageal squamous cell carcinoma (ESCC) from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic significance of ICs. The results were validated by immunohistochemistry of 58 ESCC tissue samples from our clinical center. RESULTS: The results of both TCGA and validation data suggested that high expression of programmed cell death 1 ligand 1 (PD-L1), T-cell immunoglobulin and mucin-domain-containing-3 (TIM3), and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) was associated with poor overall survival (OS) of patients with ESCC. Importantly, PD-L1/TIM3 or PD-L1/TIGIT was the optimal combination for predicting poor OS and short restricted mean survival time of patients with ESCC and was an independent prognostic factor. Moreover, a nomogram model constructed by PD-L1, TIM3, and TIGIT together with the primary tumor, regional lymph node, distant metastasis stage could provide a concise and precise prediction of 1-year and 2-year OS rates and median survival time. PD-L1/TIM3 or PD-L1/TIGIT had a positive correlation with CD8+ T cells. Notably, PD-1 and TIM3/TIGIT were primarily coexpressed on CD8+ tumor-infiltrating lymphocyte in patients with ESCC by multiplexed immunofluorescence. CONCLUSION: High expression of ICs was associated with poor OS of patients with ESCC. PD-L1/TIM3 and PD-L1/TIGIT were the optimal combinations for predicting OS, which might be potential targets for future ICBs therapy of ESCC.	esophagus
An updated review of the TNM classification system for cancer of the oesophagus and its complications.	Cancer of the esophagus is an aggressive cancer with high mortality. Because of the esophagus's lack of serosa and its peculiar lymphatic drainage, esophageal cancer is diagnosed in advanced stages. The eighth edition of the TNM (2017) aims to standardize care for esophageal cancer throughout the world; it includes not only patients treated with esophagectomy alone, but also those receiving neoadjuvant chemotherapy and/or radiotherapy. One new development in the eighth edition is that it establishes separate classifications for different time periods, with pathologic stage groups for prior to treatment (cTNM), after esophagectomy (pTNM), and after neoadjuvant therapy (ypTNM). The combined use of endoscopic ultrasound, CT, PET-CT, and MRI provides the greatest accuracy in determining the clinical stage, and these techniques are essential for planning treatment and for evaluating the response to neoadjuvant treatment. Esophagectomy continues to be the main treatment; it is also the elective gastrointestinal surgery that has the highest mortality, and it carries the risk of multiple complications, including anastomotic leaks, pulmonary complications, technical complications, and functional complications.	esophagus
Lesion human leukocyte antigen-E is associated with favourable prognosis for patients with oesophageal squamous cell carcinoma.	OBJECTIVE: To investigate the clinical significance of human leukocyte antigen (HLA)-E levels in oesophageal squamous cell carcinoma (ESCC). METHODS: The levels of HLA-E immunostaining in ESCC lesions and 47 corresponding adjacent normal tissues were measured using immunohistochemistry. The correlation between the levels of immunostaining and clinical parameters was analysed. RESULTS: This study analysed 110 paraffin-embedded primary tumour lesions and 47 case-controlled paracancerous tissues that were surgically resected from 110 patients with ESCC. Positive immunostaining for HLA-E was observed in 88.2% (97 of 110) of ESCC lesions and 29.8% (14 of 47) of normal oesophageal tissues. There was no correlation between HLA-E immunostaining in ESCC lesions and clinicopathological characteristics such as lymph node metastasis, tumour-node-metastasis stage and differentiation grade. Kaplan-Meier survival analysis revealed a significantly better prognosis in patients with higher levels of HLA-E immunostaining than in those with lower levels of HLA-E immunostaining; overall survival was 28.6 months (95% confidence interval [CI], 23.2, 34.0) versus 15.3 months (95% CI, 11.5, 19.1), respectively. Furthermore, multivariate analysis showed that the HLA-E level was an independent prognostic factor in patients with ESCC. CONCLUSION: A higher level of HLA-E immunostaining was associated with favourable survival in patients with ESCC.	esophagus
Peritumoral B cells drive proangiogenic responses in HMGB1-enriched esophageal squamous cell carcinoma.	Several B-cell subsets with distinct functions and polarized cytokine profiles that extend beyond antibody production have been reported in different cancers. Here we have demonstrated that proliferating B cells were predominantly found in the peritumoral region of esophageal squamous cell carcinoma (ESCC). These B cells were enriched in tumor nests with high expression of high-mobility group box 1 (HMGB1). High densities of peritumoral proliferating B cells and concomitantly high intratumoral HMGB1 expression showed improved prognostic significance, surpassing prognostic stratification of ESCC patients based on HMGB1 positivity alone. This striking association led us to set up models to test whether cancer-derived HMGB1 could shape tumor microenvironment via modulation on B cells. Overexpression of HMGB1 in ESCC cell lines (KYSE510 and EC18) enhanced proliferation and migration of B cells. Transcriptomic analysis showed that migratory B cells exhibited high enrichment of proangiogenic genes. VEGF expression in proliferating B cells was induced upon co-culture of HMGB1-overexpressing tumor cells and B cells. Secretome array profiling of conditioned media (CM) from the co-culture revealed rich expression of proangiogenic proteins. Consequently, incubation of human umbilical vein endothelial cells with CM promoted angiogenesis in tube formation and migration assays. HMGB1 inhibitor, glycyrrhizin, abolishes all the observed proangiogenic phenotypes. Finally, co-injection of B cells and CM with HMGB1-overexpressing tumor cells, but not with glycyrrhizin, significantly enhanced tumor growth associated with increased microvascular density in ESCC xenograft mice model. Our results indicate that cancer-derived HMGB1 elevates angiogenesis in ESCC by shifting the balance toward proangiogenic signals in proliferating B cells.	esophagus
Timing of oral intake after esophagectomy: A narrative review of the literature and case report.	Esophagectomy, a treatment modality for esophageal cancer, is associated with high rates of morbidity, the most common being anastomotic leaks and pulmonary complications. The current standard of care for nutrition support after esophagectomy includes a period of nothing by mouth with enteral nutrition support via jejunostomy tube owing to the concern of increasing the risk of anastomotic leak as a result of early postoperative oral intake. However, the optimal timing of oral diet initiation remains controversial. This narrative review presents a patient who incurred an anastomotic leak following esophagectomy after initiation of oral intake on postoperative day 5 and evaluates the current literature on the timing of oral diet initiation after esophagectomy. A systematic literature search was performed to assess current evidence evaluating early oral diet (EOD) initiation after esophagectomy. Over the past 5 years, 11 studies have evaluated the impact of EOD initiation after esophagectomy in comparison with a conventional feeding regimen, including a period of nothing by mouth with enteral or parenteral nutrition support. The available evidence suggests that EOD initiation does not increase rates of complications after esophagectomy. However, the evidence is limited by the lack of a standardized definition of what constitutes EOD initiation, patient selection bias, variations in nutrition support provided in the studies, and lack of statistical analyses evaluating the impact of potential confounding variables. Additional research with larger, high-quality randomized controlled trials is needed to determine the optimal timing of diet initiation after esophagectomy.	esophagus