crossing96/oncoscreening huggingface dataset:
Association of phosphoenolpyruvate carboxykinase 1 protein kinase activity-dependent sterol regulatory element-binding protein 1 activation with prognosis of oesophageal carcinoma.	BACKGROUND: Metabolic enzymes have non-canonical functions and play vital roles in the regulation of various cellular activities. Phosphoenolpyruvate carboxykinase 1 (PCK1), a gluconeogenic enzyme, was recently identified as an AKT-dependent protein kinase and promoted sterol regulatory element-binding protein 1 (SREBP1)-dependent lipogenesis. However, association of this protein kinase activity of PCK1 with progression of oesophageal squamous cell carcinoma (ESCC) is unclear. METHODS: We examined 200 ESCC patient samples and prognosis using immunohistochemistry, multivariate Cox regression and Kaplan-Meier Plot analyses. RESULTS: We show that the expression levels of AKT pS473, AKT-regulated PCK1 pS90, PCK1-mediated INSIG1 pS207/INSIG2 pS151 and nuclear SREBP1 were higher in analysed 200 human ESCC specimens than in their adjacent non-tumour tissues; the expression levels of these proteins were significantly and positively correlated with each other in tumour specimens. In addition, the expression levels of PCK1 pS90, INSIG1 pS207/INSIG2 pS151 and SREBP1 were associated with the tumour, node and metastasis stage and progression in ESCC. Importantly, levels of PCK1 pS90 or INSIG1 pS207/INSIG2 pS151 or nuclear SREBP1 were positively correlated with poor prognosis in patients with ESCC, and the combined expression values of PCK1 pS90, INSIG1 pS207/INSIG2 pS151 and nuclear SREBP1 had a better prognostic value than that of each individual protein expression value and was an independent prognostic marker for ESCC. CONCLUSION: These findings reveal the role of PCK1 protein kinase activity-dependent SREBP1 activation in ESCC progression. The regulation of SREBP1 by AKT activation-dependent PCK1 protein kinase activity may provide the potential for the diagnosis and treatment of human ESCC.	esophagus
Long-term endoscopic surveillance for Barrett's esophagus in Japan: Multicenter prospective cohort study.	OBJECTS: Although a recent study showed the cancer incidence of Barrett's esophagus (BE) to be 1.2%/year in 251 patient-years in Japan, the long-term outcomes remain unclear. The present study estimated the cancer risk of BE in Japan using our original prospective multicenter cohort. METHODS: A total of 98 patients with BE of maximum length of ≥2 cm were enrolled during the period of 2010-2012 and received at least one follow-up endoscopy over 5 years thereafter. Cancer incidence rates with 95% confidence interval for occurrence of esophageal adenocarcinoma (EAC) were calculated as the number of events divided by patient-years of follow-up and were expressed as %/year. RESULTS: Overall, the median endoscopic follow-up period was 59.9 (first and third quartiles, 48.5-60.8) months, constituting a total of 427 patient-years of observation. Since two EAC cases developed, the cancer incidence was 0.47% (0.01%-1.81%)/year. The cancer incidence was 0.39% (-0.16% to 2.44%) in 232 patient-years and 0.31% (-0.13% to 1.95%)/year in 318 patient-years for 55 cases with specialized intestinal metaplasia and 70 with BE ≥3 cm (maximum), respectively. At the end of follow-up, 12 of 92 patients (13.0%) died, but none died from EAC. CONCLUSION: This is the largest prospective follow-up study with endoscopy to investigate the incidence of EAC in unequivocal BE with the maximum length of ≥2 cm in Japan. Although a further large-scale study will be required to validate our results, the cancer risk of BE in Japan would be lower than previously reported (0.47% vs 1.2%/year).	esophagus
Real-time artificial intelligence for endoscopic diagnosis of early esophageal squamous cell cancer (with video).	BACKGROUND AND AIMS: Endoscopic diagnosis of early esophageal squamous cell cancer (ESCC) is complicated and dependent on operators' experience. This study aimed to develop an artificial intelligence (AI) model for automatic diagnosis of early ESCC. METHODS: Non-magnifying and magnifying endoscopic images of normal/noncancerous lesions, early ESCC, and advanced esophageal cancer (AEC) were retrospectively obtained from Qilu Hospital of Shandong University. A total of 10,988 images from 5075 cases were chosen for training and validation. Another 2309 images from 1055 cases were collected for testing. One hundred and four real-time videos were also collected to evaluate the diagnostic performance of the AI model. The diagnostic performance of the AI model was compared with endoscopists by magnifying images and the assistant efficiency of the AI model for novices was evaluated. RESULTS: The AI diagnosis for non-magnifying images showed a per-patient accuracy, sensitivity, and specificity of 99.5%, 100%, 99.5% for white light imaging, and 97.0%, 97.2%, 96.4% for optical enhancement/iodine straining images. Regarding diagnosis for magnifying images, the per-patient accuracy, sensitivity, and specificity were 88.1%, 90.9%, and 85.0%. The diagnostic accuracy of the AI model was similar to experts (84.5%, P = 0.205) and superior to novices (68.5%, P = 0.005). The diagnostic performance of novices was significantly improved by AI assistance. When it comes to the diagnosis for real-time videos, the AI model showed acceptable performance as well. CONCLUSIONS: The AI model could accurately recognize early ESCC among noncancerous mucosa and AEC. It could be a potential assistant for endoscopists, especially for novices.	esophagus
Adaptation of endovascular technique of self-expandable metal esophageal stent implantation in palliative treatment of malignant dysphagia in the course of esophageal and bronchial cancers: A one-center study.	BACKGROUND: Esophageal stent implantation is an alternative for microjejunostomy or total parenteral nutrition in the palliative treatment of malignant dysphagia in the course of esophageal and advanced bronchial cancers infiltrating the esophagus. The procedure of implanting an esophageal self-expanding metal stent (SEMS) is performed with gastroscopic guidance under general anesthesia. OBJECTIVES: To analyze the efficacy and safety of a simplified technique (without gastroscopic guidance in local anesthesia) of esophageal SEMS implantation in patients with malignant dysphagia in the course of esophageal and bronchial cancers. MATERIAL AND METHODS: This is a retrospective analysis of consecutive procedures of uncovered esophageal SEMS implantation performed with a simplified adaptation of the endovascular technique (Seldinger wire) in patients with esophageal and bronchial cancers and poor performance status. The procedures were done in a single surgical center over an 8-year period in 27 patients who were referred from oncology departments with esophageal stenosis confirmed using gastroscopy and who were being treated for malignant dysphagia. The study endpoints were effectiveness (a decrease in dysphagia from grade 3 or 4 to grade 1 after the procedure) and complications related to the procedures (including restenosis and stent migration). RESULTS: In all 27 patients, the SEMS were effectively implanted, enabling enteral nutrition after the procedure. No early complications related to the procedure were observed. A single patient developed restenosis 14 days after the procedure, which required re-stenting. CONCLUSIONS: The simplified method for SEMS implantation described herein may be considered an option in the palliative treatment of patients with malignant dysphagia in the course of esophageal and bronchial cancers and poor performance status, especially in facilities with limited access to endoscopy.	esophagus
Prediction of lymph node metastases using pre-treatment PET radiomics of the primary tumour in esophageal adenocarcinoma: an external validation study.	OBJECTIVES: To improve clinical lymph node staging (cN-stage) in oesophageal adenocarcinoma by developing and externally validating three prediction models; one with clinical variables only, one with positron emission tomography (PET) radiomics only, and a combined clinical and radiomics model. METHODS: Consecutive patients with fluorodeoxyglucose (FDG) avid tumours treated with neoadjuvant therapy between 2010 and 2016 in two international centres (n = 130 and n = 60, respectively) were included. Four clinical variables (age, gender, clinical T-stage and tumour regression grade) and PET radiomics from the primary tumour were used for model development. Diagnostic accuracy, area under curve (AUC), discrimination and calibration were calculated for each model. The prognostic significance was also assessed. RESULTS: The incidence of lymph node metastases was 58% in both cohorts. The areas under the curve of the clinical, radiomics and combined models were 0.79, 0.69 and 0.82 in the developmental cohort, and 0.65, 0.63 and 0.69 in the external validation cohort, with good calibration demonstrated. The area under the curve of current cN-stage in development and validation cohorts was 0.60 and 0.66, respectively. For overall survival, the combined clinical and radiomics model achieved the best discrimination performance in the external validation cohort (X(2) = 6.08, df = 1, p = 0.01). CONCLUSION: Accurate diagnosis of lymph node metastases is crucial for prognosis and guiding treatment decisions. Despite finding improved predictive performance in the development cohort, the models using PET radiomics derived from the primary tumour were not fully replicated in an external validation cohort. ADVANCES IN KNOWLEDGE: This international study attempted to externally validate a new prediction model for lymph node metastases using PET radiomics. A model combining clinical variables and PET radiomics improved discrimination of lymph node metastases, but these results were not externally replicated.	esophagus
MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma.	Standard-of-care, first-line therapy for patients with advanced HER2+ gastric/gastroesophageal junction adenocarcinoma is chemotherapy plus trastuzumab, a monoclonal antibody (mAb) targeting HER2. Margetuximab is an Fc-optimized mAb that binds HER2. Retifanlimab, a humanized IgG4 mAb, binds to PD-1 and blocks its interaction with PD-L1/2. Tebotelimab, an IgG4κ bispecific DART(®) molecule, binds PD-1 and lymphocyte activation gene 3 concomitantly, disrupting these nonredundant inhibitory pathways to further restore exhausted T-cell function. Here, we describe the design and rationale of the randomized, open-label, Phase II/III MAHOGANY trial evaluating margetuximab plus retifanlimab with/without chemotherapy and margetuximab plus tebotelimab with chemotherapy in first-line unresectable metastatic/locally advanced gastroesophageal junction adenocarcinoma. Primary end points include objective response rate, overall survival and safety/tolerability. Clinical trial registration: NCT04082364 (ClinicalTrials.gov).	esophagus
Secretory Phospholipase A(2) Inhibition Attenuates Adhesive Properties of Esophageal Barrett's Cells.	BACKGROUND: Gastroesophageal reflux and Barrett's esophagus are significant risk factors for the development of esophageal adenocarcinoma. Group IIa secretory phospholipase A(2) (sPLA(2)) catalyzes the production of various proinflammatory metabolites and plays a critical role in promoting reflux-induced inflammatory changes within the distal esophagus. We hypothesized that inhibition of sPLA(2) in human Barrett's cells would attenuate adhesion molecule expression via decreased activation of nuclear factor kappa B (NF-κB) and decrease cell proliferation, possibly mitigating the invasive potential of Barrett's esophagus. MATERIALS AND METHODS: Normal human esophageal epithelial cells (HET1A) and Barrett's cells (CPB) were assayed for baseline sPLA(2) expression. CPB cells were treated with a specific inhibitor of sPLA(2) followed by tumor necrosis factor-α. Protein expression was evaluated using immunoblotting. Cell proliferation was assessed using an MTS cell proliferation assay kit. Statistical analysis was performed using the Student's t-test or analysis of variance, where appropriate. RESULTS: CPB cells demonstrated higher baseline sPLA(2) expression than HET1A cells (P = 0.0005). Treatment with 30 μM sPLA(2) inhibitor significantly attenuated intercellular adhesion molecule-1 (P = 0.004) and vascular cell adhesion molecule-1 (P < 0.0001) expression as well as decreased NF-κB activation (P = 0.002). sPLA(2) inhibition decreased cell proliferation in a dose-dependent manner (P < 0.001 for 15, 20, and 30 μM doses). CONCLUSIONS: sPLA(2) inhibition in human Barrett's cells decreases cellular adhesive properties and NF-κB activation as well as decreases cell proliferation, signifying downregulation of the inflammatory response and possible attenuation of cellular malignant potential. These findings identify sPLA(2) inhibition as a potential chemopreventive target for premalignant lesions of the esophagus.	esophagus
Clinical study of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen in the treatment of advanced esophageal cancer.	OBJECTIVE: this study aimed to investigate the clinical efficacy and feasibility of the treatment of advanced esophageal cancer with a combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen. METHODS: forty-five patients with advanced esophageal cancer were enrolled and were randomly divided into two groups: a treatment group and a control group. Patients in the treatment group were treated with a 125I particle-integrated esophageal covered stent and hyperbaric oxygen, while patients in the control group were treated with a 125I particle-integrated esophageal covered stent. The clinical effects and long-term survival time of the two groups were observed. RESULTS: in the treatment group, the complete remission (CR) rate and partial remission (PR) rate of local lesions were 19.2 % and 61.5 %, respectively, and the total effective rate was 80.7 %. In the control group, the CR rate and PR rate of local lesions were 10.5 % and 52.6 %, respectively, and the total effective rate was 63.1 %. The total effective rate was higher in the treatment group than in the control group, which was statistically significant (p < 0.05). CONCLUSION: the combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen shows a good short- and long-term efficacy in the treatment of advanced esophageal cancer.	esophagus
Oesophageal cancer magnitude and presentation in Ethiopia 2012-2017.	The aim of this study was to assess the magnitude, socio-demographic, and clinical characteristics of oesophageal cancer patients in selected referral hospitals of Ethiopia. A retrospective document review was employed in ten referral hospitals in different regions of Ethiopia. A structured data extraction tool was used to extract data from clinical care records of all clinically and pathologically confirmed oesophageal cancer patients who were diagnosed and treated in those hospitals from 2012 to 2017. During the study period, a total of 777 oesophageal cancer cases were identified, and the median age of these patients was 55 years, with an interquartile range of 19. More than half (55.1%, n = 428) of the cases were males, and the majority of them were reported from Oromia (49.9%, n = 388) and Somali (25.9%, n = 202) regional states. The highest numbers of oesophageal cancer cases were recorded in 2016 (23.8%, n = 185), while the lowest were in 2012 (12.6%, n = 98). Eighty per cent of oesophageal cancer cases were diagnosed in later stages of the disease. More than one-fourth (27.0%, n = 210) of patients had surgical procedures where the majority (74.3%, n = 156) required insertion of a feeding tube followed by transhiatal oesophagectomy (10.9%, n = 23). Of the 118 patients for which there was histology data, squamous cell carcinoma (56.7%, n = 67) and adenocarcinoma (36.4%, n = 43) were the predominant histologic type. One-fourth (25.0%, n = 194) of the patients were alive, and more than two-thirds (71.7%, n = 557) of the patients' current status was unknown at the time of the review. In these referral hospitals of Ethiopia, many oesophageal cancer patients presented during later stages of the disease and needed palliative care measures. The number of patients seen in Oromia and Somali hospitals by far exceeded hospitals of the other regions, thus postulating possibly unique risk factors in those geographic areas.	esophagus
Genomic and transcriptomic alterations associated with drug vulnerabilities and prognosis in adenocarcinoma at the gastroesophageal junction.	Adenocarcinoma at the gastroesophageal junction (ACGEJ) has dismal clinical outcomes, and there are currently few specific effective therapies because of limited knowledge on its genomic and transcriptomic alterations. The present study investigates genomic and transcriptomic changes in ACGEJ from Chinese patients and analyzes their drug vulnerabilities and associations with the survival time. Here we show that the major genomic changes of Chinese ACGEJ patients are chromosome instability promoted tumorigenic focal copy-number variations and COSMIC Signature 17-featured single nucleotide variations. We provide a comprehensive profile of genetic changes that are potentially vulnerable to existing therapeutic agents and identify Signature 17-correlated IFN-α response pathway as a prognostic marker that might have practical value for clinical prognosis of ACGEJ. These findings further our understanding on the molecular biology of ACGEJ and may help develop more effective therapeutic strategies.	esophagus
Cellular Nrf2 Levels Determine Cell Fate during Chemical Carcinogenesis in Esophageal Epithelium.	Nrf2 is essential for cytoprotection against carcinogens, and through systemic Nrf2 knockout mice, Nrf2-deficient cells were shown to be susceptible to chemical carcinogens and prone to developing cancers. However, the oncogenic potential of Nrf2-deficient epithelial cells surrounded by normal cells in the esophagus could not be assessed by previous models, and the fate of Nrf2-deficient cells in such situations remains elusive. In this study, therefore, we generated mice that harbor almost equal levels of cells with Nrf2 deleted and those with Nrf2 intact in the basal layer of the esophageal epithelium, utilizing inducible Cre-mediated recombination of Nrf2 alleles in adults through moderate use of tamoxifen. In this mouse model, epithelial cells with Nrf2 deleted were maintained with no obvious decrease or phenotypic changes for 12 weeks under unstressed conditions. Upon exposure to the carcinogen 4-nitroquinoline-1-oxide (4NQO), the cells with Nrf2 deleted accumulated DNA damage and selectively disappeared from the epithelium, so almost all 4NQO-induced tumors originated from cells with Nrf2 intact and not from those with Nrf2 deleted. We propose that cells with Nrf2 deleted do not undergo carcinogenesis due to selective elimination upon exposure to 4NQO, indicating that cellular Nrf2 abundance and the epithelial environment determine the cell fate or oncogenic potential of esophageal epithelial cells in 4NQO-induced carcinogenesis.	esophagus
MicroRNA Profiling in Oesophageal Adenocarcinoma Cell Lines and Patient Serum Samples Reveals a Role for miR-451a in Radiation Resistance.	Many patients with Oesophageal Adenocarcinoma (OAC) do not benefit from chemoradiotherapy treatment due to therapy resistance. To better understand the mechanisms involved in resistance and to find potential biomarkers, we investigated the association of microRNAs, which regulate gene expression, with the response to individual treatments, focusing on radiation. Intrinsic radiation resistance and chemotherapy drug resistance were assessed in eight OAC cell lines, and miRNA expression profiling was performed via TaqMan OpenArray qPCR. miRNAs discovered were either uniquely associated with resistance to radiation, cisplatin, or 5-FU, or were common to two or all three of the treatments. Target mRNA pathway analyses indicated several potential mechanisms of treatment resistance. miRNAs associated with the in vitro treatment responses were then investigated for association with pathologic response to neoadjuvant chemoradiotherapy (nCRT) in pre-treatment serums of patients with OAC. miR-451a was associated uniquely with resistance to radiation treatment in the cell lines, and with the response to nCRT in patient serums. Inhibition of miR-451a in the radiation resistant OAC cell line OE19 increased radiosensitivity (Survival Fraction 73% vs. 87%, p = 0.0003), and altered RNA expression. Pathway analysis of effected small non-coding RNAs and corresponding mRNA targets suggest potential mechanisms of radiation resistance in OAC.	esophagus
Cost-effectiveness analysis of thoracoscopic versus open esophagectomy for esophageal cancer: a population-based study.	The question as to whether the clinical benefits of video-assisted thoracoscopic esophagectomy (VATE) do outweigh its increased costs remains unanswered. Here, we analyzed the cost-effectiveness of VATE versus open esophagectomy (OE) in a real-world setting. Using 2008-2015 Taiwanese Health Insurance claim data, we identified 3271 patients with esophageal cancer who underwent transthoracic esophagectomy. By taking into account nine confounding variables, we constructed a 1:1 propensity score-matched sample of patients who underwent VATE or OE (n = 629 each). Direct costs incurred within three years after surgery and survival were analyzed. There were no significant intergroup differences in terms of R0 resection rates, length of stay, as well as 30- and 90-day mortality and unplanned readmission rates. However, the number of dissected nodes was higher in the VATE group (median: 24 vs. 18, P < 0.001). While VATE had higher index hospitalization costs (median, 12331 USD vs. 10730 USD, P < 0.001), cost differences were reduced over time. The average accumulated cost person-month of VATE declined below that of OE at 14 months after hospital discharge. Overall survival (OS) figures were more favorable for patients treated with VATE (3-year OS: 47% vs. 41%; life expectancy: 4.04 life-years [LY] vs. 3.30 LY). The cost-effectiveness plane showed that only 0.3% of all VATE procedures were more costly and less effective than OE. The probabilities for VATE to be cost-effective at the willingness-to-pay (WTP) thresholds of 10000 and 50000 USD/LY were 63.5% and 92.4%, respectively. Using commonly accepted WTP thresholds, VATE was more cost-effective than OE for patients with esophageal cancer.	esophagus
Role of nodal skip metastasis in patients with mid-thoracic oesophageal squamous cell carcinoma: a propensity score matching study.	OBJECTIVES: Nodal skip metastasis (NSM) is a common phenomenon in mid-thoracic oesophageal squamous cell carcinoma (MT-OSCC); however, the prognostic implications of NSM in patients with MT-OSCC remain unclear. METHODS: This retrospective study enrolled 300 patients with MT-OSCC who underwent radical oesophagectomy and who had pathologically confirmed lymph node metastasis from January 2014 to December 2016. The patients were divided into 2 groups according to the presence or absence of NSM. Propensity score matching was applied to minimize patient selection bias. The impact of NSM on overall survival (OS) was assessed by Kaplan-Meier and multiple Cox proportional hazards analyses. The median follow-up time was 57 months. RESULTS: The NSM rate in the entire cohort was 22.0% (66/300). Pathological N (pN) stage (P < 0.001) and sex (P = 0.001) were identified as significant independent risk factors for NSM. NSM was more frequent in pN1 compared with pN2 patients (87.9% vs 12.1%, P < 0.001) and no NSM was found in pN3. NSM(+) patients had better prognoses than NSM(-) patients (Kaplan-Meier; 3-year OS, 62.1% vs 34.1%, P < 0.001). Propensity score matching produced 51 matched pairs, and the 3-year OS was still better in the NSM(+) compared with the NSM(-) group (66.7% vs 40.0%, P = 0.025). Multivariable Cox analysis confirmed NSM(+) as an independent factor favouring OS in patients with MT-OSCC. CONCLUSIONS: NSM usually occurs at pN1 stage in patients with MT-OSCC, and is associated with a favourable prognosis.	esophagus