crossing96/oncoscreening huggingface dataset:
4-Methylthio-3-butenyl isothiocyanate (MTBITC) induced apoptotic cell death and G2/M cell cycle arrest via ROS production in human esophageal epithelial cancer cells.	To investigate the chemopreventive mechanisms of 4-Methylthio-3-butenyl isothiocyanate (MTBITC), we analyzed cell viability, cell cycle distribution, and expression levels for cell cycle and apoptosis-related proteins in MTBITC-treated malignant esophageal KYSE510 cells, with and without the reactive oxygen species (ROS) scavenger N-acethyl-L-Cysteine (NAC). MTBITC dose-dependently reduced cell viability and Bcl2 protein expression, while it induced cleavages of caspase-3, caspase-9, and PARP-1, suggesting that reduced cell viability occurred through the mitochondrial apoptotic pathway in KYSE510 cells. In cell cycle distribution analysis, MTBITC (20-40 µM) induced cell cycle arrest at G2/M phase. Furthermore, MTBITC induced Chk1 and Akt phosphorylations and decreased p27 protein expression. Both apoptotic- and cell cycle-related changes induced by MTBITC treatment were abolished by NAC. These results suggest that MTBITC has chemopreventive potential for esophageal carcinogenesis by elimination of cancer cells via induction of mitochondrial apoptotic cell death, G2/M cell cycle arrest, and ROS production.	esophagus
Impact of Preoperative Skeletal Muscle Mass and Nutritional Status on Short-and Long-Term Outcomes After Esophagectomy for Esophageal Cancer: A Retrospective Observational Study : Impact of Psoas Muscle Mass and Body Mass on Esophagectomy.	BACKGROUND: Preoperative muscle volume and body mass index (BMI) are associated with postoperative outcomes. Because esophagectomy for esophageal cancer (EC) is associated with high morbidity and because EC has a poor prognosis, this study investigated the association of preoperative skeletal muscle mass and nutritional status with postoperative outcomes. METHODS: The study analyzed 483 patients who underwent esophagectomy from 2009 to 2012. The cross-sectional area of the psoas muscle index (PMI) was measured at the third lumbar vertebral level using computed tomography. Clavien-Dindo classifications were used to analyze postoperative complications. Because skeletal muscle mass varies according to sex, all analyses were performed accordingly (390 males, 93 females). RESULTS: For male patients, BMI was a significant multivariate factor, and PMI, a univariate factor, predicted postoperative complications and overall survival (OS). Using a preoperative nutritional and muscular (PNM) score derived from BMI and PMI results (patients were allocated 1 point if their BMI was < 18.5 kg/m(2) and 1 point if their PMI was < 600 mm(2)/m(2), for a possible maximum total of 2 points), male patients were categorized as high risk (score 2), moderate risk (score 1), or low risk (score 0). In the low-risk group, anastomotic leakage was significantly less (p = 0.01), and the 3-year OS was significantly better (p < 0.01). On the other hand, in female patients, neither BMI nor PMI was a significant factor for postoperative outcomes. CONCLUSIONS: For male patients, the PNM score is a promising tool for predicting postoperative outcomes and identifying patients requiring preoperative nutritional intervention and rehabilitation.	esophagus
Elevated Pretreatment CEA and CA19-9 Levels are Related to Early Treatment Failure in Esophageal Adenocarcinoma.	INTRODUCTION: Chemoradiotherapy and surgery are the basis of the potentially curative treatment for esophageal cancer. Approximately 1 in 5 patients, however, do not benefit from this intensive treatment due to early treatment failure. The aim of this study was to evaluate levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 at diagnosis, in relation to survival and early treatment failure (disease recurrence or death within 1 year after surgery). METHODS: Patients with esophageal adenocarcinoma scheduled for chemoradiotherapy followed by surgery between 1998 and 2014 were selected from a retrospectively collected database if both CEA and CA19-9 levels were measured before the start of treatment. RESULTS: Pretreatment CEA and CA19-9 levels were known in 102 patients. Median overall survival differed (P<0.001) between patients with normal levels of both CEA and CA19-9 (n=59; 51 mo), patients with elevated CEA only (n=13; 43 mo), patients with elevated CA19-9 only (n=19; 24 mo), and those with elevated levels of both CEA and CA19-9 (n=11; 11 mo). Elevation of both CEA and CA19-9 was associated with early treatment failure (odds ratio: 10.4; 95% confidence interval: 2.4-45.5, P=0.002). Median time to tumor recurrence was 34 months in patients with normal CEA and CA19-9 levels, and 7 months in those with elevated levels of both (P=0.003). CONCLUSIONS: Pretreatment elevated CEA and CA19-9 levels were significantly associated with early treatment failure and decreased overall survival in this esophageal adenocarcinoma patient cohort treated with curative intent. Until prospective validation, CEA and CA19-9 might play a role in identifying high-risk patients before the start of intensive locoregional therapy.	esophagus
Impact of isolated tumor cells in regional lymph nodes in adeno-and squamous cell carcinoma of the esophagus and the esophagogastric junction-A systematic review.	BACKGROUND/INTRODUCTION: Isolated tumor cells (ITC) are tumor cells identified in the regional lymph nodes of patients with adeno- or squamous cell carcinoma of the esophagogastric junction (EGJ) or the esophagus. The current staging guidelines for these cancers do not assign any prognostic relevance to ITC, but their role remains debatable. We evaluated current literature to provide an overview of the prognostic relevance of ITC in regional lymph nodes of patients diagnosed with node negative cancer of the esophagus and EGJ. METHODS: A systematic search of several databases according to PRISMA guidelines. Three main criteria for inclusion were selected: 1. The studies had to include a group of patients with histopathologically identified ITC as defined by the Union for International Cancer Control Tumor, Node, Metastasis-classification 8(th) edition. 2. The studies had to include a group of patients classified as pN0. 3. The studies had to present the survival rate of patients with pN0, ITC. RESULTS: A total of five studies met the inclusion criteria. Combined, the studies included 434 pN0-patients of which 88 patients had ITC when evaluating the lymph nodes more extensively. The rate of ITC varied from 8% to 56% between studies. Significant differences in surgical techniques, neoadjuvant treatment and histological subtypes were observed. Three studies found a significant prognostic impact of ITC while one did not, and one had conflicting results. The largest difference in 5-year-survival was 33% for patients with ITC compared with 60% without ITC. CONCLUSION: Although, the results were conflicting, ITC appeared to be a negative prognostic factor in esophageal and EGJ cancer. However, heterogeneity between the studies did not allow for a definitive conclusion.	esophagus
The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic.	Esophageal adenocarcinoma (EAC) is a poor-prognosis cancer type with rapidly rising incidence. Understanding of the genetic events driving EAC development is limited, and there are few molecular biomarkers for prognostication or therapeutics. Using a cohort of 551 genomically characterized EACs with matched RNA sequencing data, we discovered 77 EAC driver genes and 21 noncoding driver elements. We identified a mean of 4.4 driver events per tumor, which were derived more commonly from mutations than copy number alterations, and compared the prevelence of these mutations to the exome-wide mutational excess calculated using non-synonymous to synonymous mutation ratios (dN/dS). We observed mutual exclusivity or co-occurrence of events within and between several dysregulated EAC pathways, a result suggestive of strong functional relationships. Indicators of poor prognosis (SMAD4 and GATA4) were verified in independent cohorts with significant predictive value. Over 50% of EACs contained sensitizing events for CDK4 and CDK6 inhibitors, which were highly correlated with clinically relevant sensitivity in a panel of EAC cell lines and organoids.	esophagus
Effect of restrictive fluid therapy with hydroxyethyl starch during esophagectomy on postoperative outcomes: a retrospective cohort study.	BACKGROUND: To improve prognosis after esophageal surgery, intraoperative fluid optimization is important. Herein, we hypothesized that hydroxyethyl starch administration during esophagectomy reduce the total amount of fluid infused and it could have a positive effect on postoperative complication occurrence and mortality. METHODS: All consecutive adult patients who underwent elective esophageal surgery for cancer were studied. The primary outcome was the development of composite complications including death, cardio-cerebrovascular complications, respiratory complications, renal complications, gastrointestinal complications, sepsis, empyema or abscess, and multi-organ failure. The relationship between perioperative variables and composite complication was evaluated using multivariable logistic regression. RESULTS: Of 892 patients analyzed, composite complications developed in 271 (30.4%). The higher hydroxyethyl starch ratio in total fluid had a negative relationship with the total fluid infusion amount (r = - 0.256, P <  0.001). In multivariable analysis, intraoperatively administered total fluid per weight per hour (odds ratio, 1.248; 95% CI, 1.153-1.351; P <  0.001) and HES-to-crystalloid ratio (odds ratio, 2.125; 95% CI, 1.521-2.969; P <  0.001) were associated with increased risks of postoperative composite outcomes. CONCLUSIONS: Although hydroxyethyl starch administration reduces the total fluid infusion amount during esophageal surgery for cancer, intravenous hydroxyethyl starch infusion is associated with an increasing risk of postoperative composite complications.	esophagus
A competing-risks nomogram and recursive partitioning analysis for cause-specific mortality in patients with esophageal neuroendocrine carcinoma.	The objective of this study is to estimate the probability of cause-specific mortality using a competing-risks nomogram and recursive partitioning analysis in a large population-based cohort of patients with esophageal neuroendocrine carcinoma. The surveillance, epidemiology and end results database was used to identify 162 patients diagnosed with esophageal neuroendocrine carcinoma from 1998 to 2014. We estimated a cumulative incidence function for cause-specific mortality. A nomogram was constructed by using a proportional subdistribution hazard model, validated using bootstrap cross-validation, and evaluated with a decision curve analysis to assess its clinical utility. Finally, we performed risk stratification using a recursive partitioning analysis to divide patients with esophageal neuroendocrine carcinoma into clinically useful prognostic groups. Tumor location, distant metastasis, surgery, radiotherapy, and chemotherapy were significantly associated with cause-specific mortality. The calibration plots demonstrated good concordance between the predicted and actual outcomes. The discrimination performance of a Fine-Gray model was evaluated by using the c-index, which was 0.723 for cause-specific mortality. The decision curve analysis ranged from 0.268 to 0.968 for the threshold probability at which the risk model provided net clinical benefits relative to hypothetical all-screening and no-screening scenarios. The risk groups stratified by a recursive partitioning analysis allowed significant distinction between cumulative incidence curves. We determined the probability of cause-specific mortality in patients with esophageal neuroendocrine carcinoma and developed a nomogram and recursive partitioning analysis stratification system based on a competing-risks model. The nomogram and recursive partitioning analysis appear to be suitable for risk stratification of cause-specific mortality in patients with esophageal neuroendocrine carcinoma and will help clinicians to identify patients at increased risk of cause-specific mortality to guide treatment and surveillance decisions.	esophagus
Comprehensive bioinformation analysis of methylated and differentially expressed genes in esophageal squamous cell carcinoma.	Differentially methylated genes (DMGs) play a crucial role in the etiology and pathogenesis of esophageal squamous cell carcinoma (ESCC). This study aimed to ascertain aberrant DMGs and pathways by comprehensive bioinformatics analysis. We downloaded the gene expression microarray of GSE51287 from the Gene Expression Omnibus (GEO). Aberrant DMGs were obtained using the GEO2R tool. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses were performed on selected genes by using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed with the Retrieval of Interacting Genes (STRING) and visualized in Cytoscape. Then, the modules in the PPI networks were analyzed with Molecular Complex Detection, and the hub genes derived from the PPI networks were verified by using the Cancer Genome Atlas. A total of 271 DMGs, including 173 hypermethylated genes, were enriched in the biological processes of peptidyl-tyrosine phosphorylation, positive regulation of transcription from RNA polymerase II promoters, and autophosphorylation. Pathway analysis enrichment revealed cancer, PI3K-Akt, and Ras signaling pathways, and 98 hypomethylated genes were enriched in the biological processes of the immune response, extracellular matrix disassembly, and macrophage differentiation. Pathway enrichment showed rheumatoid arthritis, cytokine-cytokine receptor interaction, and toxoplasmosis. Furthermore, bioinformatics analysis indicated feasible aberrant DMGs and pathways in ESCC. The results provided valuable information on the pathogenesis of ESCC. The significant DMGs may provide novel insights into their potential predictive and prognostic value as methylation-based biomarkers for the precise diagnosis and treatment of ESCC.	esophagus
Tumor budding in laryngeal carcinoma.	BACKGROUND: Tumor budding was defined as a single cancer cell or a cluster of fewer than five cancer cells in the stroma of the invasive tumor margin. It has been suggested as a prognostic factor in various cancers, such as esophageal, lung, colorectal, and endometrial. There are only a few studies about the prognostic signifi cance of tumor budding in laryngeal carcinomas. MATERIALS AND METHODS: A total of 81 patients with laryngeal carcinoma diagnosed between 2011 and 2016 and treated by partial or total laryngectomy were evaluated. Clinicopathologic parameters were correlated with the presence and grade of tumor budding. RESULTS: The study was consisted of 77 (95.1%) male and 4 (4.9%) female patients. The mean age of the patients was 60.2 years (min: 42 and max: 78). Median follow-up time was 25 months (min: 7 and max: 54) (SD ±11.5). Histopathologic diagnosis was squamous cell carcinoma (SCC) in all patients. Of the 62 cases showing budding, 2 (3.2%) were stage 1, 12 (19.4%) stage 2, 16 (25.8%) stage 3, and 32 (51.6%) were stage 4. Fifteen cases with budding (24.2%) showed lymphovascular invasion (LVI). None of the nonbudding cases had LVI and perineural invasion (PNI). Statistical analysis revealed that LVI and PNI were signifi cantly associated with budding (P = 0.017 and P = 0.012). Among the tumors showing budding, 37% had lymph node metastasis (LNM). In nonbudding cases 15% had LNM. There was a statistically significant correlation between LNM and budding (P = 0.017). None of the parameters correlated with grade of tumor budding statistically. CONCLUSION: The results of this study suggest that tumor budding might be used as a prognostic factor in laryngeal SCCs.	esophagus
[Expression of PLOD2 in esophageal squamous cell carcinoma and its correlation with invasion and metastasis].	Objective: To investigate PLOD2 expression in esophageal squamous cell carcinoma, and to explore the potential mechanism by which PLOD2 promotes tumor metastasis. Methods: The expression of PLOD2 in 60 cases of esophageal squamous cell carcinoma (the patients were collected at the first Affiliated Hospital of Xinxiang Medical University, from January 2016 to December 2017) was investigated by immunohistochemistry. Fibrillar collagen formation and collagen deposition were detected by picrosirius red staining. Correlation of PLOD2 expression with clinical pathologic features of the patients was performed using χ(2) test and Kaplan-Meier analysis. After EC-109 cells were transfected with LV-vector and LV-over/PLOD2, the expression of PLOD2 was detected by real time PCR and the impact of POLD2 on invasion in EC-109 cells was determined by transwell migration and invasion assays. The expression of PLOD2/AKT epithelial-to-mesenchymal transition signal pathway related proteins was detected by Western blot. Results: The expression level of PLOD2 in esophageal squamous cell carcinoma was 81.7% (49/60 cases),higher than their paired noncancerous tissues(8.3%, 5/60; P<0.01), and correlated significantly with tumor depth of invasion and nodal metastasis (P<0.01). Picrosirius red staining showed that collagen deposition was increased and the degree of fibrillar organization was enhanced in carcinoma tissues that had higher PLOD2 expression. Transwell migration and invasion assays showed that PLOD2 significantly promoted the migration and invasion ability of EC-109 cells. Western blot showed that PLOD2 significantly increased the expression levels of p-FAK, p-AKT and vimentin in EC-109 cells. Conclusions: Esophageal squamous cell carcinoma has a high expression of PLOD2 that correlates with tumor invasion and lymph node metastasis. PLOD2 promotes invasion and metastasis of esophageal squamous cell carcinoma through epithelial-to-mesenchymal transition via FAK/AKT signal pathway.	esophagus
Radiosensitivity nomogram based on circulating neutrophils in thoracic cancer.	AIM: To evaluate the prediction ability of neutrophils and develop a nomogram on radiosensitivity in thoracic cancer patients. METHODS: We retrospectively reviewed 398 lung and esophageal cancers patients who received external-beam radiotherapy or concurrent chemoradiotherapy as first-line therapy. RESULTS: Logistic regression model showed that patients with low levels of neutrophil counts and/or TGF-β1 exhibited better radiation sensitivity. Furthermore, a nomogram was created to predict radiotherapy sensitivity. The combination of neutrophil count and TGF-β1 level was an independent prognostic factor for lung and esophageal cancers patients. CONCLUSION: The study developed a nomogram based on the levels of circulating neutrophils and TGF-β1. The prediction value in radiosensitivity and protumorigenic effect of neutrophils might owe to N2 tumor-associated neutrophils.	esophagus
[Two-Stage Reconstruction Surgery with Free Jejunum Graft for Necrosis of the Gastric Tube Following Subtotal Esophagectomy-A Case Report].	The case is a 73-year-old man who underwent esophagectomy and retrosternal gastric conduit reconstruction for esophageal cancer. Reoperation was performed because the oral side of the gastric tube developed necrosis on the 31st postoperative day. The necrotic parts of the gastric tube were resected, and a cervical esophageal stoma was created. The remaining gastric tube was pulled up at the anterosternal subcutaneous location in preparation for the two-stage reconstructive operation. The reconstructive operation with a free jejunum graft through the anterosternal subcutaneous route was performed 35 days after the reoperation. Vascular anastomosis was performed with the right internal thoracic artery and vein by microsurgery. The postoperative course was satisfactory. Necrosis of the gastric tube is a rare and severe complication of esophagectomy. Reconstructive surgery for gastric tube necrosis is generally necessary but difficult to perform because of the severe surgical stress it confers on the patient. In this paper, we showed a new approach for two-stage reconstruction with a free jejunum graft through the anterosternal subcutaneous route. This operative procedure causes relatively less surgical stress than other procedures; hence, it is considered to be a beneficial reconstructive approach for patients with gastric tube necrosis.	esophagus
[A Case Receiving Gastric Tube Resection for the Recurrence after a Proton Beam Irradiation in a Patient with Gastric Tube Cancer after Esophagectomy].	A 74-year-oldman underwent transthoracic esophagectomy andgastric tube reconstruction for esophageal cancer 15 years ago. Eleven years after the esophagectomy, he was diagnosedwith gastric tube cancer. He receivedproton beam irradiation therapy. Macroscopic clinical effect revealed complete response at that time. Four years later, due to his discomfort symptom, he was diagnosedwith recurrent gastric tube cancer. Total resection of the gastric tube was performedat our hospital. In pathology findings, poorly differentiated adenocarcinoma was found at the proton beam irradiated part with multiple lymph node metastases in the omentum. He died 8 months postoperatively because of carcinomatous pleurisy. Periodic screening of the gastric tube and early detection of gastric tube cancer at early stage are important.	esophagus
[A Case of Esophagogastric Junction Adenocarcinoma with Multiple Esophageal Intramural Metastases].	We experienced a case of multiple esophageal intramural metastasis from adenocarcinoma of the esophagogastric junction. A 58-year-old man was admitted complaining of dysphagia. Upper gastrointestinal endoscopy revealed a type 3 tumor at the esophagogastric junction. Biopsy showed Group 5, poorly differentiated adenocarcinoma. Abdominal CT indicated regional and para-aortic lymph node metastasis. Then the clinical diagnosis was established as Siewert type Ⅲ adenocarcinoma and cT4aN2M1(LYM), cStage Ⅳ. After conducting 4 courses of SP(S-1/cisplatin)therapy, endoscopy showed partial response of the primary tumor and the submucosal nodules in the lower esophagus. We performed lower esophagectomy and total gastrectomy by left thoracotomy and laparotomy. Six esophageal nodules were identified in the lower esophagus, and pathological examination proved the poorly differentiated adenocarcinoma. The esophageal tumors were diagnosed as intramural metastases. The patient showed hepatic and lymphatic recurrence 9 months after surgery, and died 15 months after surgery. Esophageal intramural metastasis from esophagogastric junction adenocarcinoma is relatively rare. We discuss this case along with a review of the literature.	esophagus