crossing96/oncoscreening huggingface dataset:
Sarcopenia as a prognostic factor for survival in patients with locally advanced gastroesophageal adenocarcinoma.	BACKGROUND AND AIMS: Patients with gastric cancer often show signs of malnutrition. We sought to evaluate the influence of sarcopenia in patients with locally advanced, not metastasized, gastric or gastro-esophageal junction (GEJ) cancer undergoing curative treatment (perioperative chemotherapy and surgery) on morbidity and mortality in order to identify patients in need for nutritional intervention. PATIENTS AND METHODS: Two-centre study, conducted in the Frankfurt University Clinic and Krankenhaus Nordwest (Frankfurt) as part of the University Cancer Center Frankfurt (UCT). 47/83 patients were treated in the FLOT trial (NCT01216644). Patients´ charts were reviewed for clinical data. Two consecutive CT scans were retrospectively analyzed to determine the degree of sarcopenia. Survival was calculated using the Kaplan-Meier method, multivariate analysis was performed using the Cox regression. RESULTS: 60 patients (72.3%) were male and 23 (27.7%) female. 45 patients (54.2%) had GEJ type 1-3 and 38 (45.8%) gastric tumors, respectively. Sarcopenic patients were significantly older than non-sarcopenic patients (mean age 65.1 years vs. 59.5 years, p = 0.042), terminated the chemotherapy significantly earlier (50% vs. 22.6%, p = 0.037) and showed higher Clavien-Dindo scores, indicating more severe perioperative complications (score ≥3 43.3 vs. 17.0%, p = 0.019). Sarcopenic patients had a significantly shorter survival than non-sarcopenic patients (139.6 ± 19.5 [95% CI, 101.3-177.9] vs. 206.7 ± 13.8 [95% CI, 179.5-233.8] weeks, p = 0.004). Multivariate Cox regression analysis showed that, besides UICC stage, sarcopenia significantly influenced survival. CONCLUSION: Sarcopenia is present in a large proportion of patients with locally advanced gastric or GEJ cancer and significantly influences tolerability of chemotherapy, surgical complications and survival.	esophagus
ACSS2/AMPK/PCNA pathway‑driven proliferation and chemoresistance of esophageal squamous carcinoma cells under nutrient stress.	Although platinum‑based chemotherapy is the first‑line choice for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients, accelerated recurrence and chemoresistance remain inevitable. New evidence suggests that metabolism reprogramming under stress involves independent processes that are executed with a variety of proteins. This study investigated the functions of nutrient stress (NS)‑mediated acetyl‑CoA synthetase short‑chain family member 2 (ACSS2) in cell proliferation and cisplatin‑resistance and examined its combined effects with proliferating cell nuclear antigen (PCNA), a key regulator of DNA replication and repair. Here, it was demonstrated that under NS, when the AMP‑activated protein kinase (AMPK) pathway was activated, ESCC cells maintained proliferation and chemoresistance was distinctly upregulated as determined by CCK‑8 assay. As determined using immunoblotting and RT‑qPCR, compared with normal esophageal epithelial cells (Het‑1A), ESCC cells were less sensitive to NS and showed increased intracellular levels of ACSS2. Moreover, it was shown that ACSS2 inhibition by siRNA not only greatly interfered with proliferation under NS but also participated in DNA repair after cisplatin treatment via PCNA suppression, and the acceleration of cell death was dependent on the activation of the AMPK pathway as revealed by the Annexin V/PI and TUNEL assay results. Our study identified crosstalk between nutrient supply and chemoresistance that could be exploited therapeutically to target AMPK signaling, and the results suggest ACSS2 as a potential biomarker for identifying higher‑risk patients.	esophagus
Anastomotic Techniques and Associated Morbidity in Total Minimally Invasive Transthoracic Esophagectomy: Results From the EsoBenchmark Database.	OBJECTIVE: The aim of this study was to describe anastomotic techniques used for total minimally invasive transthoracic esophagectomy (ttMIE) and to analyze the associated morbidity. BACKGROUND: ttMIE faces increasing application in surgical treatment of esophageal cancer. For esophagogastric reconstruction, different anastomotic techniques are currently used, but their effect on postoperative anastomotic leakage and morbidity has not been investigated. PATIENTS AND METHODS: Patients were selected from a basic dataset, collected during a 5-year period from 13 international surgical high-volume centers. Endpoints were anastomotic leakage rate and postoperative morbidity in correlation to anastomotic techniques, measured by the Clavien-Dindo classification and the Comprehensive Complication Index (CCI). RESULTS: Five anastomotic techniques were identified in 966 patients after ttMIE: intrathoracic end-to-side circular-stapled technique in 427 patients (double-stapling n = 90, purse-string n = 337), intrathoracic (n = 109) or cervical (n = 255) side-to-side linear-stapled, and cervical end-to-side hand-sewn (n = 175). Leakage rates were similar in intrathoracic and cervical anastomoses (15.9% vs 17.2%, P = 0.601), but overall complications (56.7%% vs 63.7%, P = 0.029) and median 90-day CCI {21 [interquartile range (IQR) 0-36] vs 29 [IQR 0-40], P = 0.019} favored intrathoracic reconstructions. Leakage rates after intrathoracic end-to-side double-stapling (23.3%) and cervical end-to-side hand-sewn (25.1%) techniques were significantly higher compared with intrathoracic side-to-side linear (15.6%), end-to-side purse-string (13.9%), and cervical side-to-side linear-stapled esophagogastrostomies (11.8%) (P < 0.001). Multivariable analysis confirmed anastomotic technique as independent predictor of leakage after ttMIE. CONCLUSION: Results of this analysis present the current status of the technical evolution of ttMIE with anastomotic leakage as predominant surgical complication. However, technique-related morbidity requires cautious interpretation considering the long learning curve of this complex surgical procedure.	esophagus
NTCP model for postoperative complications and one-year mortality after trimodality treatment in oesophageal cancer.	PURPOSE/OBJECTIVES: To develop normal tissue complication probability (NTCP) models for postoperative pulmonary and cardiac complications and one-year mortality after preoperative chemoradiotherapy and surgery in oesophageal cancer patients. METHODS: 691 patients from two institutions (2002-2017) were included; 134 treated with protons. Multivariable logistic regression analyses on 601 patients studied the predictive value of clinical/treatment-related (gender, age, body mass index (BMI), smoking, cardiac comorbidity, chronic obstructive pulmonary disease, histology, cT/N) and dosimetric variables (absolute/relative lung/heart volumes receiving or spared from xGy, mean doses, planning target volume) for the presence of pulmonary complications, cardiac complications and one-year mortality. Model validation was performed using a nonrandom split-sample of 90 patients. Model performance was assessed by AUC and calibration plots. RESULTS: Respectively 144/601 (24.0%) and 165/601 (27.5%) patients developed a pulmonary or cardiac complication. For pulmonary complications, an NTCP model with optimism-corrected AUC of 0.75 (95%CI = 0.73-0.76) was obtained. The model contained mean lung dose (OR = 1.15, 95%CI = 1.09-1.22, p < 0.001), increasing age (OR = 1.03, 95%CI = 1.01-1.06, p = 0.002), BMI (OR = 1.04, 95%CI = 0.99-1.08, p = 0.084) and squamous cell carcinoma (OR = 3.22, 95%CI = 1.97-5.24, p < 0.001) as predictors. In validation, AUC of 0.79 was obtained (calibration slope 1.26). For cardiac complications, only age (OR = 1.06, 95%CI = 1.04-1.09, p < 0.001) with optimism-corrected AUC of 0.67 (95%CI = 0.65-0.68) was selected. For one-year mortality, an NTCP model with optimism-corrected AUC of 0.63 (95%CI = 0.58-0.66) was obtained. Lung absolute V(35) (OR = 1.0016, 95%CI = 1.0007-1.0026, p = 0.001), cN (OR = 2.45, 95%CI = 1.18-5.09, p = 0.017), cT4 (OR = 2.51, 95%CI = 1.10-5.74, p = 0.029) and cardiac comorbidity (OR = 2.91, 95%CI = 1.46-5.77, p = 0.002) were selected as predictors. At validation, AUC of 0.57 was obtained (calibration slope 0.75). CONCLUSION: We were able to build and validate NTCP models for the presence of a postoperative pulmonary complication and for one-year mortality after trimodality treatment in oesophageal cancer.	esophagus
[Understanding of the lower mediastinal lymph node dissection in the adenocarcinoma of the esophagogastric junction through abdomino-transhiatal approach].	In recent years, the incidence of adenocarcinoma of esophagogastric junction (AEG) keeps increasing. Siewert type II and type III AEG invades at 2-4 cm in the lower esophagus, and it has a higher rate of lower mediastinal lymph node metastasis. Lower mediastinal lymph node clearing through the abdomino-transhiatal (TH) approach is preferred, which can be accomplished by entering the lower mediastinum through the hiatus and mobilize the esophagus upward and the surrounding lymph and connective tissue for approximately 6.5 cm. Using the infracardiac bursa (IBC) as an anatomical landmark improves the safety and operability of the thorough dissection of the lower mediastinum. Total resection of the mesenterium at the esophagogastric junction can entirely dissect the lower mediastinal lymph nodes, which conforms to the safety principles in oncology.	esophagus
IL-8 is involved in radiation therapy resistance of esophageal squamous cell carcinoma via regulation of PCNA.	Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. Our present study revealed that the expression of IL-8 was increased in radiation therapy resistance of ESCC cells. Targeted inhibition of IL-8 by its neutralization antibody (anti-IL-8) can re-sensitize ESCC cells to radiation therapy and suppress the expression of proliferating cell nuclear antigen (PCNA). IL-8 can regulate the expression of PCNA via modulating its mRNA stability and promoter activity. Mechanistically, IL-8 can regulate the expression of miR-27b-5p, which can directly bind with 3'UTR of PCNA to decrease its mRNA stability. Further, anti-IL-8 can decrease the expression of transcription factor YY1, which can bind with the promoter of PCNA to increase its transcription. Taken together, our data revealed that IL8 can regulate the radiation resistance of ESCC cells and expression of PCNA. It suggested that targeted inhibition of IL-8 may improve the clinical treatment efficiency of radio therapy.	esophagus
Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly invasive malignant tumor and the majority of patients have advanced stage of ESCC at diagnosis with poor outcome. Identification of sensitive and specific biomarkers for early screening of ESCC is critical for improving patient overall survival. METHODS: Pyrosequencing was used to determine the magnitude of DNA methylation on the selected regions PAX1 (paired box gene1), SOX1(sex determining region Y-box-1), and ZNF582 (zinc finger protein 582) in ESCC. RESULTS: The methylation levels ofPAX1, SOX1, and ZNF582 genes were significantly higher in the cancerous tissues compared to those in the non-cancerous (all P < 0.0001). The accuracy, sensitivity and specificity of PAX1 methylation for the detection of cancer were respectively 0.754, 96.0% and 51.4%; for SOX1 which were 0.781, 89.2% and 59.5%; for ZNF582 which were 0.898, 93.2% and 75.7%. Most importantly, both the sensitivity and specificity of ZNF582 methylation testing achieved 100% in female ESCC patients. Hypermethylation of PAX1/SOX1/ZNF582 exhibited as an independent risk factor for ESCC development. In addition, ZNF582 methylation level in tumor tissue from the female patients was higher than that from male patients, and it was higher in the moderate and poor differentiated tumors compared to that in well-differentiated tumors. SOX1 methylation level was significantly higher in tumors located in the upper region than those located in the middle or lower regions. CONCLUSION: The methylation levels ofPAX1, SOX1 and ZNF582 genes were all higher in cancer tissues than in paired-adjacent and normal tissues, suggesting that detection of PAX1/SOX1/ZNF582 methylation status may serve as a promising biomarker for ESCC screening and diagnosis.	esophagus
Prognostic value of (18)F-FDG PET/MR imaging biomarkers in oesophageal squamous cell carcinoma.	PURPOSE: To correlate the clinical stage and prognosis of oesophageal squamous cell carcinoma (SCC) using the imaging biomarkers from integrated positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS: In total, 54 consecutive patients with oesophageal SCC who receive PET/MRI scan were recruited before treatment. The imaging biomarkers used were the mean and minimal apparent diffusion coefficients (ADC(mean) and ADC(min)), standardized uptake value (SUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of tumours. The correlation between each imaging biomarker and survival was investigated using the Cox proportional hazards model. RESULTS: ADC(mean) was negatively correlated with SUV(max) (r = -0.414, P =  0.025). ADC(min) was negatively correlated with SUV(max) (r = -0.423, P =  0.001) and SUV(peak) (r = -0.402, P =  0.003), and was significantly lower in M1 than in M0 tumours (829.6 vs. 1069.8, P = 0.005). MTV was significantly higher in T3 + (P <  0.001), N1 + (P = 0.014) and TNM stage III + (P <  0.001) tumours. TLG was significantly higher in T3 + (P <  0.001), N1 + (P <  0.001), M1 (P =  0.045) and TNM stage III + (P <  0.001) tumours. The MTV/ADC(min) ratio exhibited the highest area under the receiver operating characteristic curve (AUROC) for predicting M1 and advanced TNM stage tumours. Multivariate analysis for progression-free survival (PFS) and overall survival (OS) showed that a larger MTV/ADC(min) was associated with a shorter PFS and OS (P = 0.024 and 0.046, respectively). CONCLUSION: The imaging biomarkers in integrated PET/MRI may predict clinical stage and survival in patients with oesophageal SCC.	esophagus
Variation in receipt of therapy and survival with provider volume for medical oncology in non-curative esophago-gastric cancer: a population-based analysis.	BACKGROUND: While surgical care by high-volume providers for esophago-gastric cancer (EGC) yields better outcomes, volume-outcome relationships are unknown for systemic therapy. We examined receipt of therapy and outcomes in the non-curative management of EGC based on medical oncology provider volume. METHODS: We conducted a population based retrospective cohort study of non-curative EGC over 2005-2017 by linking administrative healthcare datasets. The volume of new EGC consultations per medical oncology provider per year was calculated and divided into quintiles. High-volume (HV) medical oncologists were defined as the 4-5th quintiles. Outcomes were receipt of chemotherapy and overall survival (OS). Multivariate logistic and Cox-proportional hazards regressions examined the association between management by HV medical oncologist, receipt of systemic therapy, and OS. RESULTS: 7011 EGC patients with non-curative management consulted with medical oncology. 1-year OS was superior for HV medical oncologists (> 11 patients/year), with 28.4% (95% CI 26.7-30.2%) compared to 25.1% (95% CI 23.8-26.3%) for low volume (p < 0.001). After adjusting for age, sex, comorbidity burden, rurality, income quintile, and diagnosis year, HV medical oncologist was independently associated with higher odds of receiving chemotherapy (OR 1.13, 95% CI 1.01-1.26), and independently associated with superior OS (HR 0.89, 95% CI 0.84-0.93). CONCLUSIONS: Medical oncology provider volume was associated with variation in non-curative management and outcomes of EGC. Care by an HV medical oncologist was independently associated with higher odds of receiving chemotherapy and superior OS, after adjusting for case mix. This information is important to inform disease care pathways and care organization; an increase in the number of HV medical oncologists may reduce variation and improve outcomes.	esophagus
The risk of venous thromboembolism after surgery for esophagogastric malignancy and the impact of chemotherapy: a population-based cohort study.	To define the incidence of postoperative venous thromboembolism (VTE) and effects of chemotherapy in a population undergoing surgery for esophagogastric cancer. This population-based cohort study used linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data from England to identify subjects undergoing esophageal or gastric cancer surgery between 1997 and 2014. Exposures included age, comorbidity, smoking, body mass index, and chemotherapy. Crude rates and adjusted hazard ratios (HRs) were calculated for rate of first postoperative VTE using Cox regression models. The cumulative incidence of VTE at 1 and 6 months was estimated accounting for the competing risk of death from any cause. Of the 2,452 patients identified, 1,012 underwent gastrectomy (41.3%) and 1,440 esophagectomy (58.7%). Risk of VTE was highest in the first month, with absolute VTE rates of 114 per 1,000 person-years (95% CI 59.32-219.10) following gastrectomy and 172.73 per 1,000 person-years (95% CI 111.44-267.74) following esophagectomy. Neoadjuvant and adjuvant chemotherapy was associated with a six-fold increased risk of VTE following gastrectomy, HR 6.19 (95% CI 2.49-15.38). Cumulative incidence estimates of VTE at 6 months following gastrectomy in patients receiving no chemotherapy was 1.90% and esophagectomy 2.21%. However, in those receiving both neoadjuvant and adjuvant chemotherapy, cumulative incidence following gastrectomy was 10.47% and esophagectomy, 3.9%. VTE rates are especially high in the first month following surgery for esophageal and gastric cancer. The cumulative incidence of VTE at 6 months is highest in patients treated with chemotherapy. In this category of patients, targeted VTE prophylaxis may prove beneficial during chemotherapy treatment.	esophagus
Identification of serum microRNAs predicting the response of esophageal squamous-cell carcinoma to nivolumab.	BACKGROUND: Nivolumab, a programmed cell death protein 1 (PD-1) inhibitor, showed promising activity for the treatment of advanced esophageal squamous-cell carcinoma in a phase II study (ONO-4538-07; JapicCTI-No.142422). We explored serum microRNA (miRNA) candidate predictive markers of the response to nivolumab. METHODS: In the phase II study, 19 patients received nivolumab (3 mg/kg IV Q2W) at National Cancer Center Hospital. The expression of 2565 serum miRNAs before and during treatment was analyzed using a 3D-Gene Human miRNA Oligo Chip (Toray Industries, Inc.). Immune-related response evaluation criteria used to evaluate response and miRNA expression were compared between responders and non-responders. The top 20 miRNAs by accuracy in receiver operating characteristic curve analysis were identified by leave-one-out cross-validation, and those with the area under curve values > 0.8, cross-validated accuracy > 0.8, and a 0.5 difference in the average log2 expression level between responders and non-responders were further analyzed. RESULTS: Of the 19 patients, five responded to nivolumab. We identified miRNAs related to the response to nivolumab, including one detected in the serum before treatment (miR-1233-5p; AUC = 0.895) and three present after treatment (miR-6885-5p, miR-4698 and miR-128-2-5p; AUC = 0.93, 0.97 and 0.93, respectively). CONCLUSIONS: Candidate miRNAs capable of predicting the response to nivolumab were identified in the serum of patients with advanced esophageal squamous-cell carcinoma in ONO-4538-07.	esophagus
Palliative resection or radiation of primary tumor prolonged survival for metastatic esophageal cancer.	PURPOSE: We aimed to explore the value of palliative resection or radiation of primary tumor for metastatic esophageal cancer (EC) patients. METHODS: Surveillance, Epidemiology, and End Results database was used for identifying metastatic EC patients. The patients were divided into resection and nonresection groups. And patients without resection were divided into radiation and nonradiation groups. Propensity score matching (PSM) analyses were adopted to reduce the baseline differences between the groups. Cancer specific survivals (CSSs) and overall survivals (OSs) were compared by Kaplan-Meier (K-M) curves. Multivariable analyses by COX proportion hazards model were performed to identify risk factors for CSS and OS. Predictive nomograms were conducted according to both postoperative factors and preoperative factors. RESULTS: A total of 7982 metastatic EC patients were selected for our analyses. After PSM, 978 patients were included in the survival analyses comparing palliative resection and nonresection. The CSS and OS for patients underwent palliative resection were significantly longer than those without resection (median CSS: 21 months vs 7 months, P < .001; median OS: 20 months vs 7 months, P < .001). In the overall population without resection, 654 patients were matched for radiation and nonradiation groups. And K-M curves showed that patients with radiation had longer CSS and OS than those without radiation (median CSS: 11 months vs 6 months, P < .001; median OS: 10 months vs 6 months, P < .001). Nomograms were generated for prediction of 1-, 2-, and 3-year CSS and OS. All C-indexes implied moderate discrimination and accuracy. And all nomograms had good calibration. CONCLUSION: Palliative resection or radiation of primary tumor could prolong CSS and OS of metastatic EC patients.	esophagus
Promoter methylation and clinical significance of GPX3 in esophageal squamous cell carcinoma.	BACKGROUND: Glutathione peroxidase 3 (GPX3) provides critical protection against reactive oxygen species (ROS) in cells. Downregulation of GPX3 may contribute to carcinogenesis of esophageal squamous cell carcinoma (ESCC), but the mechanisms are not clear. MATERIALS AND METHODS: We examined the differences in gene expression between ESCC and normal esophageal epithelial, by using GEO datasets, and collected 136 ESCC tumors and adjacent normal tissues to confirm our findings. GPX3 expression was measured, at the mRNA and protein levels, by qRT-PCR, Western Blot and immunohistochemistry (IHC). RESULTS: GPX3 mRNA and protein levels were 3.3-fold higher in normal epithelium compared with case-matched ESCC tissues. There was no significant correlation between clinical parameters and expression levels of GPX3 in ESCC. Promoter methylation of the GPX3 gene correlated with decreased expression. CONCLUSION: Downregulation of GPX3 might be a key factor in the process of ESCC carcinogenesis.	esophagus