crossing96/oncoscreening huggingface dataset:
Identification of miRNAs as prognostic factors for esophageal squamous cell carcinoma.	Objective: The prognostic value of microRNAs for esophageal squamous cell carcinoma (ESCC) is still not be well identified. Methods: The microRNA expression profiles of 119 paired ESCC tissue samples and para-carcinoma tissues from GEO database under accession number of GSE43732. A mutation information based feature selection method was applied to identify the discriminative microRNAs between paired ESCC tissues and para-carcinoma tissues. Results: In para-carcinoma tissues, patients had better survival with higher has-miR-410 (log-rank p = 0.0123), has-miR-411-5p (log-rank p = 0.0152), has-miR-193b-5p (log-rank p = 0.0188) and has-miR-4486 (log-rank p = 0.0307) expression levels. When compared with para-carcinoma tissues, there has more correlations between miRNA expression levels and survival in tumor tissues. We identified 20 potential miRNAs associated with prognosis. Besides, a heatmap was draw to explore miRNA expression levels in tumor tissues and survival. Conclusions: The present study identified 24 miRNAs in 119 paired ESCC tissue samples and para-carcinoma tissues, including 4 miRNAs in para-carcinoma tissues and 20 in tumor tissues, respectively. The dysregulation of these miRNAs were associated with different outcomes. We thought this study could provide novel noninvasive early biomarkers for ESCC patients.	esophagus
Review of early endoscopic findings in patients with local recurrence after definitive chemoradiotherapy for esophageal squamous cell carcinoma.	BACKGROUNDS: Local recurrence after definitive chemoradiotherapy, if diagnosed early, can be cured by salvage endoscopic therapy, which allows organ preservation and contributes to maintaining patient quality of life. This study aimed to investigate early endoscopic findings of local recurrence in post-definitive chemoradiotherapy patients. METHODS: Between January 2008 and June 2012, 17 esophageal squamous cell carcinoma patients with no metastasis but local recurrence after definitive chemoradiotherapy were enrolled. We attempted to find endoscopic hallmarks suggestive of local recurrence by comparing pre- and post-local recurrence diagnostic images. The influence of follow-up schedule on chosen salvage therapy type was also investigated. RESULTS: Endoscopic local recurrence findings included eight submucosal tumors, five ulcers, and four erosions. Upon review of prior images, findings suggestive of local recurrence were detected in seven patients, including six submucosal tumors and one erosion, all of which were smaller than 10 mm. These lesions had changed morphologically at local recurrence diagnosis: three submucosal tumors had become larger and three submucosal tumors and one erosion had changed to ulcers. Of 12 patients with cT1 at local recurrence, four (33%) underwent follow-up endoscopy within 1 month of local recurrence findings and 11 patients (92%) were treated with salvage endoscopic therapy. CONCLUSIONS: Endoscopists should be aware that SMTs or erosions, even those smaller than 10 mm, can indicate local recurrence after complete response to definitive chemoradiotherapy. Follow-up endoscopy should be performed within 1-2 months if findings suggestive of local recurrence are observed on prior endoscopy, even when biopsy results are negative.	esophagus
A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle Progression.	nc886 is a regulatory non-coding RNA (ncRNA) whose expression is frequently silenced in malignancies. In the case of esophageal squamous cell carcinoma (ESCC), nc886 silencing is associated with shorter survival of patients, suggesting nc886's tumor suppressor role in ESCC. However, this observation has not been complemented by an in-detail study about nc886's impact on gene expression and cellular phenotypes. Here we have shown that nc886 inhibits AKT, a key protein in a renowned pro-survival pathway in cancer. nc886-silenced cells (nc886(-) cells) have activated AKT and altered expression of cell cycle genes. nc886(-) cells tend to have lower expression of CDKN2A and CDKN2C, both of which are inhibitors for cyclin-dependent kinase (CDK), and higher expression of CDK4 than nc886-expressing cells. As a result, nc886(-) cells are hyperactive in the progression of the G1 to S cell cycle phase, proliferate faster, and are more sensitive to palbociclib, which is a cancer therapeutic drug that targets CDK4/6. Experimentally by nc886 expression and knockdown, we have determined the AKT target genes and cell cycle genes that are controlled by nc886 (nc886-associated gene sets). These gene sets, in combination with pathologic staging and nc886 expression levels, are a vastly superior predictor for the survival of 108 ESCC patients. In summary, our study has elucidated in ESCC how nc886 inhibits cell proliferation to explain its tumor suppressor role and identified gene sets that are of future clinical utility, by predicting patient survival and responsiveness to a therapeutic drug.	esophagus
Circumferential intramural esophageal dissection with large mucosal defect.	Intramural esophageal dissection (IED) is an uncommon entity characterized by mucosal rupture creating a false lumen. It usually develops following endoscopy or in old patients with bleeding tendencies and spontaneous presentation possesses diagnostic dilemma. Managing partial IED is simpler than circumferential IED. Due to rarity of presentation, management is not standardized. We report circumferential IED in a young patient and challenges faced during diagnosis and management.	esophagus
Wee1 Kinase Inhibitor AZD1775 Effectively Sensitizes Esophageal Cancer to Radiotherapy.	PURPOSE: Esophageal cancer is a deadly malignancy with a 5-year survival rate of only 5% to 20%, which has remained unchanged for decades. Esophageal cancer possesses a high frequency of TP53 mutations leading to dysfunctional G(1) cell-cycle checkpoint, which likely makes esophageal cancer cells highly reliant upon G(2)-M checkpoint for adaptation to DNA replication stress and DNA damage after radiation. We aim to explore whether targeting Wee1 kinase to abolish G(2)-M checkpoint sensitizes esophageal cancer cells to radiotherapy. EXPERIMENTAL DESIGN: Cell viability was assessed by cytotoxicity and colony-forming assays, cell-cycle distribution was analyzed by flow cytometry, and mitotic catastrophe was assessed by immunofluorescence staining. Human esophageal cancer xenografts were generated to explore the radiosensitizing effect of AZD1775 in vivo. RESULTS: The IC(50) concentrations of AZD1775 on esophageal cancer cell lines were between 300 and 600 nmol/L. AZD1775 (100 nmol/L) as monotherapy did not alter the viability of esophageal cancer cells, but significantly radiosensitized esophageal cancer cells. AZD1775 significantly abrogated radiation-induced G(2)-M phase arrest and attenuation of p-CDK1-Y15. Moreover, AZD1775 increased radiation-induced mitotic catastrophe, which was accompanied by increased γH2AX levels, and subsequently reduced survival after radiation. Importantly, AZD1775 in combination with radiotherapy resulted in marked tumor regression of esophageal cancer tumor xenografts. CONCLUSIONS: Abrogation of G(2)-M checkpoint by targeting Wee1 kinase with AZD1775 sensitizes esophageal cancer cells to radiotherapy in vitro and in mouse xenografts. Our findings suggest that inhibition of Wee1 by AZD1775 is an effective strategy for radiosensitization in esophageal cancer and warrants clinical testing.	esophagus
Radiofrequency ablation for low-grade dysplasia in Barrett's esophagus: long-term outcome of a randomized trial.	BACKGROUND AND AIMS: A prior randomized study (Surveillance versus Radiofrequency Ablation study [SURF study]) demonstrated that radiofrequency ablation (RFA) of Barrett's esophagus (BE) with confirmed low-grade dysplasia (LGD) significantly reduces the risk of esophageal adenocarcinoma. Our aim was to report the long-term outcomes of this study. METHODS: The SURF study randomized BE patients with confirmed LGD to RFA or surveillance. For this retrospective cohort study, all endoscopic and histologic data acquired at the end of the SURF study in May 2013 until December 2017 were collected. The primary outcome was rate of progression to high-grade dysplasia (HGD)/cancer. All 136 patients randomized to RFA (n = 68) or surveillance (n = 68) in the SURF study were included. After closure of the SURF study, 15 surveillance patients underwent RFA based on patient preference and study outcomes. RESULTS: With 40 additional months (interquartile range, 12-51), the total median follow-up from randomization to last endoscopy was 73 months (interquartile range, 46-85). HGD/cancer was diagnosed in 1 patient in the RFA group (1.5%) and in 23 in the surveillance group (33.8%) (P = .000), resulting in an absolute risk reduction of 32.4% (95% confidence interval [CI], 22.4%-44.2%) with a number needed to treat of 3.1 (95% CI, 2.3-4.5). Seventy-five of 83 patients (90%; 95% CI, 82.1%-95.0%) treated with RFA for BE reached complete clearance of BE and dysplasia. BE recurred in 7 of 75 patients (9%; 95% CI, 4.6%-18.0%), mostly minute islands or tongues, and LGD in 3 of 75 (4%; 95% CI, 1.4%-11.1%). CONCLUSIONS: RFA of BE with confirmed LGD significantly reduces the risk of malignant progression, with sustained clearance of BE in 91% and LGD in 96% of patients, after a median follow-up of 73 months. (Clinical trial registration number: NTR1198.).	esophagus
The Impact of Adjuvant Therapy on Survival After Esophagectomy for Node-negative Esophageal Adenocarcinoma.	OBJECTIVE: Determine whether adjuvant chemotherapy is associated with a survival benefit in high risk T2-4a, pathologically node-negative distal esophageal adenocarcinoma. SUMMARY OF BACKGROUND DATA: There is minimal literature to substantiate the NCCN guidelines recommending adjuvant therapy for patients with distal esophageal adenocarcinoma and no pathologic evidence of nodal disease. METHODS: The National Cancer Database was used to identify adult patients with pT2-4aN0M0 esophageal adenocarcinoma who underwent definitive surgery (2004-2015) and had characteristics considered high risk by the NCCN. Patients were stratified by receipt of adjuvant chemotherapy with or without radiation. The primary outcome was overall survival, which was evaluated using Kaplan-Meier and multivariable Cox Proportional Hazards models. A 1:1 propensity score-matched analysis was also performed to compare survival between the groups. RESULTS: Four hundred three patients met study criteria: 313 (78%) without adjuvant therapy and 90 who received adjuvant chemotherapy with or without radiation (22%). In both unadjusted and multivariable analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit compared to no adjuvant therapy. In a subgroup analysis of 335 patients without high risk features by NCCN criteria, adjuvant chemotherapy was not independently associated with a survival benefit. CONCLUSION: In this analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit in completely resected, pathologically node-negative distal esophageal adenocarcinoma, independent of presence of high risk characteristics. The risks and benefits of adjuvant therapy should be weighed before offering it to patients with completely resected pT2-4aN0M0 esophageal adenocarcinoma.	esophagus
Immunotherapy for esophageal cancer: a 2019 update.	Esophageal cancer remains a global health concern with a dismal prognosis and an estimated 5-year survival rate of approximately 10-15%. Immunotherapy is a novel treatment approach representing an effective and promising option against several types of cancer. The development of new and efficacious immunotherapeutic strategies, such as adoptive cell therapy-based, antibody-based and vaccine-based therapies, aims to prevent immunological escape and modify immunological responses. In this review, we discuss the theoretical background and current status of immunotherapy for patients with esophageal cancer. We also present ongoing clinical trials and summarize key findings concerning survival and safety analyses.	esophagus
Diagnosis and Endoscopic Treatment of Gastrointestinal Stromal Tumors Arising from Esophagus.	Aim: The primary purpose of this study was to investigate the diagnosis and endoscopic treatment of gastrointestinal stromal tumors (GISTs) arising from esophagus. Materials and Methods: From January 2013 to December 2017, 16 cases of GISTs of esophagus were retrospectively identified from a total of >3000 GISTs treated in our center. Demographic characteristics, clinical data, endoscopic therapy outcomes, histopathology, and follow-up were analyzed. Results: The mean age of the patients was 53 years (range 35-71 years), mostly female (56.3%). Seven tumors were in the lower esophagus, five in the middle esophagus, and one in the upper esophagus. The most common symptom was abdominal discomfort (8/16; 50.0%), followed by acid reflux (6/16; 37.5%). All of the patients underwent CT scan, gastroscopy, and/or endoscopic ultrasound. Two patients were diagnosed with esophageal GISTs with a preoperative endoscopic biopsy. Tumors were resected completely in all patients by endoscopic surgery. The median operating time was 85 minutes (range 28-153 minutes), and the average tumor size was 11.6 mm (range 6-21 mm). Postoperative histopathology demonstrated esophageal GISTs were positive for CD117 and CD34. The mean length of postoperative hospital stay was 4.7 days (range 2-7 days). The median postoperative follow-up duration was 28 months (range 1-59 months). Conclusion: Endoscopic treatment seems to be safe and effective for tumors size <20 mm in diameter. However, long-term prospective randomized controlled trials are further needed.	esophagus
Prediagnostic adult body mass index change and esophageal adenocarcinoma survival.	BACKGROUND: We examined whether body mass index (BMI) changes in adulthood, prior to disease onset, are associated with overall survival among esophageal adenocarcinoma patients. METHODS: We included 285 histologically confirmed patients with a complete baseline BMI questionnaire. Using extended Cox regression models, we obtained adjusted hazard ratios (HRs) for the associations between overall survival and BMI at diagnosis, BMI 6 months before diagnosis, self-reported average adult BMI, and ΔBMI (BMI 6 months before diagnosis minus average adult BMI), categorized into tertiles <0 kg/m(2) (BMI loss), ≥0 and <1.25 kg/m(2) (stable BMI), and ≥1.25 kg/m(2) (BMI gain). We also assessed interaction between ΔBMI and average adult BMI (≥ kg/m(2) versus <27.5 kg/m(2) ) with overall survival. RESULTS: Body mass index at diagnosis >25 and <35 kg/m(2) was associated with better overall survival. Compared to patients with stable BMI in adulthood, patients who gained BMI throughout adulthood had 1.68 times the all-cause hazard of death (95% CI: 1.17-2.43; P < .01), independent of diagnosis BMI and percent weight loss 6 months before diagnosis. Compared to patients with average adult BMI < 27.5 who maintained stable adult BMI, patients with average adult BMI ≥ 27.5 kg/m(2) who gained BMI had the worst survival (HR = 3.05; 95% CI 1.62-5.72; P < .01). CONCLUSION: Body mass index gain in adulthood is associated with poor overall survival, and maintaining a normal body weight throughout adulthood is associated with the best overall survival among esophageal adenocarcinoma patients, independent of BMI at diagnosis.	esophagus
Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming.	Tumor cells often reprogram their metabolism for rapid proliferation. The roles of long noncoding RNAs (lncRNAs) in metabolism remodeling and the underlying mechanisms remain elusive. Through screening, we found that the lncRNA Actin Gamma 1 Pseudogene (AGPG) is required for increased glycolysis activity and cell proliferation in esophageal squamous cell carcinoma (ESCC). Mechanistically, AGPG binds to and stabilizes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). By preventing APC/C-mediated ubiquitination, AGPG protects PFKFB3 from proteasomal degradation, leading to the accumulation of PFKFB3 in cancer cells, which subsequently activates glycolytic flux and promotes cell cycle progression. AGPG is also a transcriptional target of p53; loss or mutation of TP53 triggers the marked upregulation of AGPG. Notably, inhibiting AGPG dramatically impaired tumor growth in patient-derived xenograft (PDX) models. Clinically, AGPG is highly expressed in many cancers, and high AGPG expression levels are correlated with poor prognosis, suggesting that AGPG is a potential biomarker and cancer therapeutic target.	esophagus
Critical appraisal of gastric conduit ischaemic conditioning (GIC) prior to oesophagectomy: A systematic review and meta-analysis.	INTRODUCTION: Anastomotic leaks remain a major complication following oesophagectomy, accounting for high morbidity and mortality. Recently, gastric ischaemic conditioning (GIC) has been proposed to improve anastomotic integrity through neovascularisation of the gastric conduit. This systematic review and meta-analysis aim to determine the impact of GIC on postoperative outcomes following oesophagectomy. METHODS: A systematic literature search was performed to identify studies reporting GIC for any indication of oesophageal resection up to April 25, 2019. The primary outcome was anastomotic leak. Secondary outcomes were conduit necrosis, anastomotic strictures, overall and major complications or in-hospital mortality. Meta-analyses were conducted using random-effects modelling. RESULTS: Nineteen studies reported on GIC, of which 13 were comparative studies. GIC was performed through ligation in 13 studies and embolisation in six studies. GIC did not appear to reduce anastomotic leakages (OR 0.80, CI(95:) 0.51-1.24, p = 0.3), anastomotic strictures (OR 0.75, CI(95:) 0.35-1.60, p = 0.5), overall complications (OR 1.02, CI(95:) 0.48-2.16, p = 0.9), major complications (OR 1.06, CI(95:) 0.53-2.11, p = 0.9), or in-hospital mortality (OR 0.70, CI(95:) 0.32-1.53, p = 0.4). However, GIC was associated with reduced rates of conduit necrosis (OR 0.30, CI(95:) 0.11-0.77, p = 0.013). CONCLUSION: GIC does not appear to reduce overall rates of anastomotic leakage after oesophagectomy but seems to reduce severity of leakages. More in depth studies are recommended.	esophagus
Tumoral Expression of CD166 in Human Esophageal Squamous Cell Carcinoma: Implications for Cancer Progression and Prognosis.	Accumulating data showed that cancer stem cells (CSCs) identified by cell surface markers contribute to the initiation, progression, and prognosis of human cancers. In this study, the expression of CSC candidates CD166, CD44, and Lgr5 in 65 cases of esophageal squamous cell carcinoma (ESCC) and 16 cases of control esophageal tissues were examined with immunohistochemistry (IHC). The correlation between tumoral expression levels of these CSC candidates and clinicopathological variables was analyzed. IHC results showed that the expression of CD166 in esophageal control tissues was completely negative, but it was in 87.69% (57/65) ESCC tissues. The expression of CD44 and Lgr5 did not differ between esophageal control tissues and ESCC tissues (p > 0.05). In addition, there were not correlations found among the expression levels of CD166, CD44, and Lgr5 in ESCC tissues. Clinicopathological analysis revealed that the tumoral expression level of CD166 correlated with lymph node involvement and TNM staging in patients with ESCC, and lower tumoral expression of CD44 was found in patients with advanced TNM staging. Kaplan-Meier survival curves suggested that expression level of CD166 appeared to have a negative impact on overall survival rate after surgery in patients with ESCC. Such impact was not found in other two CSC candidates. The authors therefore conclude that CD166 is a potential prognostic biomarker and correlates with advanced progression features in patients with ESCC.	esophagus
NME4 modulates PD-L1 expression via the STAT3 signaling pathway in squamous cell carcinoma.	NME4, also named Nm23-H4, is a contraction of NME/NM23 Nucleoside Diphosphate Kinase 4, whose major role is the synthesis of nucleoside triphosphates. However, its association with programmed death ligand 1 (PD-L1) remains far from understood. Herein, it was discovered that silencing NME4 can lead to the marked downregulation of PD-L1, with phosphorylated STAT3 at the 705th serine being inactivated in vitro in esophageal squamous cell carcinoma (ESCC) cell lines. To further validate the association between NME4 and PD-L1 that was observed in cell lines, Pearson correlation analysis was performed on the data regarding the transcriptomic RNA sequencing of NME4 and PD-L1 in cervical squamous cell carcinoma (CSCC), which pathologically highly resembles ESCC in terms of tumor origin, obtained from the GEPIA database. It was demonstrated that their correlation was significant but negative between NME4 and PD-L1 in CSCC. To the best of our knowledge, this is the first report describing a modulation exerted by NME4 over PD-L1 in the background of squamous cell carcinoma, strongly suggestive of the underlying role of NME4 working to exclude CD8 T cells from infiltrating into the squamous cell carcinoma microenvironment.	esophagus
Risk Factors for Progression of Barrett's Esophagus to High Grade Dysplasia and Esophageal Adenocarcinoma.	Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Methods of identifying BE patients at high risk for progression to high-grade dysplasia (HGD) or EAC are needed to improve outcomes and identify who will benefit most from intensive surveillance or ablative therapy. Clinical predictors of BE progression to HGD or EAC are poorly understood, with multiple contradictory studies. We performed a retrospective study which included 460 patients at Johns Hopkins Hospital who underwent at least 2 upper endoscopies 6 months apart showing biopsy-documented BE between 1992 and 2013. Patients with EAC or HGD at the initial endoscopy were excluded. Demographic, clinicopathological, and endoscopic data were collected. Univariate and multivariate Cox proportional hazards analyses with time to progression to HGD and EAC were performed. Among 460 patients included in the study, 132 BE patients developed HGD and 62 developed EAC. Significant EAC risk factors included age, abdominal obesity, caffeine intake, and the presence of HGD. Risk factors for HGD or EAC included age, caffeine intake, and low-grade dysplasia while colonic adenomas trended towards significance. Notably, a history of statin or SSRI usage reduced the risk of EAC or HGD by 49% or 61%, respectively. Our study validated several known and identified several novel risk factors, including a history of colonic adenomas or caffeine usage. Low-grade dysplasia was a risk factor for progression but various endoscopic characteristics were not, suggesting that screening strategies should focus on histology instead. We identified SSRIs as a new potentially chemoprotective medication.	esophagus