crossing96/oncoscreening huggingface dataset:
Active human papillomavirus involvement in Barrett's dysplasia and oesophageal adenocarcinoma is characterized by wild-type p53 and aberrations of the retinoblastoma protein pathway.	We have previously demonstrated that transcriptionally active high-risk HPV (hr-HPV) is strongly incriminated in Barrett's dysplasia (BD) and oesophageal adenocarcinoma (OAC) using mainly fresh frozen tissue. This study aimed to identify biomarkers of active HPV infection in Barrett's metaplasia, (BM)/BD/OAC by immunohistochemical staining (IHC) of formalin-fixed paraffin embedded (FFPE) tissue for aberrations of p53 and the retinoblastoma (pRb) pathway, which are targets for the viral oncoproteins, E6/E7, respectively. Prospectively, BM (n = 81)/BD (n = 72)/OAC (n = 65) FFPE specimens were subjected to IHC staining for pRb, p16(INK4A) , cyclin D(1) , p53 and RNA in-situ hybridization for E6/E7 transcripts. HPV DNA was determined via PCR in fresh frozen specimens. Viral load measurement (real-time PCR) and Next Generation Sequencing of TP53 was performed. Of 218 patients, 56 were HPV DNA positive [HPV16 (n = 42), 18 (n = 13), 6 (n = 1)]. Viral load was low. Transcriptionally active HPV (DNA(+) /RNA(+) ) was only found in the dysplastic and adenocarcinoma group (n = 21). The majority of HPV DNA(+) /RNA(+) BD/OAC were characterized by p 16highINK4A (14/21, 66.7%), pRb(low) (15/21, 71.4%) and p53(low) (20/21, 95%) and was significantly different to controls [combination of HPV DNA(-) /RNA(-) (n = 94) and HPV DNA(+) /RNA(-) cohorts (n = 22)]. p53(low) had the strongest association with DNA(+) /RNA(+) oesophageal lesions (OR = 23.5, 95% CI = 2.94-187.8, p = 0.0029). Seventeen HPV DNA(+) /RNA(+) BD/OAC identified as p53(low,) were sequenced and all but one exhibited wild-type status. pRb(low) /p53(low) provided the best balance of strength of association (OR = 8.0, 95% CI = 2.6-25.0, p = 0.0003) and sensitivity (71.4%)/specificity (71.6%) for DNA(+) /RNA(+) BD/OAC. Active HPV involvement in BD/OAC is characterized by wild-type p53 and aberrations of the retinoblastoma protein pathway.	esophagus
[Neoadjuvant chemoradiotherapy combined with operation vs. operation alone for resectable esophageal cancer: Meta-analysis on randomized controlled trials].	OBJECTIVE: To compare the treatment outcomes of neoadjuvant chemoradiotherapy (NCRT) combined with operation and operation alone for esophageal cancer. METHODS: Randomized controlled trials(RCTs), comparing the treatment outcomes of NCRT combined with operation to operation alone for esophageal cancer, published from January 1990 to December 2015 were searched from PubMed, Web of Science, and other English-language databases. STATA 10.0 software was used to analyze short-term efficacy (R0 resection rate, positive lymph node ratio, postoperative complications and mortality) and long-term outcomes (overall survival rate and local recurrence rate). The publication bias was evaluated by funnel plot and Egger test. RESULTS: A total of 12 RCTs, including 1 872 esophageal cancer patients, were included in the meta-analysis, with 939 cases in NCRT combined with operation group and 943 cases in operation alone group. Meta-analysis of short-term efficacy showed that, as compared to operation alone group, NCRT combined with operation group had higher R0 resection rate (RR=1.19, 95%CI:1.08 to 1.32, P=0.015), lower positive lymph node rate (RR=0.55, 95%CI:0.49 to 0.63, P=0.001), but higher postoperative mortality (RR=1.63, 95%CI:1.09 to 2.45, P=0.018). Postoperative complications were similar between the two groups(RR=1.04, 95%CI:0.91 to 1.18, P=0.558). Meta-analysis of long-term outcomes showed that, as compared to operation alone group, NCRT combined with operation group had lower local recurrence rate (RR=0.50, 95%CI:0.39 to 0.64, P=0.000), and higher overall survival rate (HR=0.75, 95%CI:0.66 to 0.84, P=0.001). Subgroup analysis according to pathological types showed that both squamous cell carcinoma and adenocarcinoma patients in NCRT combined with operation group had higher overall survival rates compared to those in operation alone group (HR=0.80, 95%CI:0.69 to 0.93, P=0.003; HR=0.78, 95%CI:0.70 to 0.88, P=0.003). CONCLUSIONS: NCRT can decrease the staging of esophageal cancer, elevate the R0 resection rate, and ameliorate local recurrence without increasing postoperative complications. Meanwhile NCRT can improve overall survival of esophageal cancer patients even with squamous cell carcinoma and adenocarcinoma.	esophagus
Nitrous oxide cryotherapy for treatment of esophageal squamous cell neoplasia: initial multicenter international experience with a novel portable cryoballoon ablation system (with video).	BACKGROUND AND AIMS: Early esophageal squamous cell neoplasia (ESCN) can be successfully treated by EMR, endoscopic submucosal dissection (ESD), or radiofrequency ablation. A new portable, battery-powered cryotherapy system using nitrous oxide (cryoballoon focal ablation system [CbFAS]) has been used for Barrett's esophagus. It consists of a small hand-held device containing liquid nitrous oxide, which converts to gas within a low-pressure-compliant through-the-scope balloon and freezes targeted mucosa in contact with the balloon. This study evaluated the feasibility of endoscopic eradication of early ESCN with the CbFAS. METHODS: Patients with early ESCN (defined as low-grade intraepithelial neoplasia [LGIN], high-grade intraepithelial neoplasia [HGIN], or early T1 squamous mucosal cancer) were treated with the CbFAS. After chromoendoscopy, all Lugol's unstained lesions (USLs) were targeted with 8, 10, or 12 seconds of ice per site, and treatment was repeated until biopsy samples demonstrated eradication of ESCN. Postprocedure adverse events were recorded. RESULTS: Ten patients (4 men; median age, 69.5 years) with LGIN (n=2), HGIN (n=7), or esophageal squamous cell carcinoma (ESCC; n=1, after EMR) in 24 USLs were treated. The median maximum diameter of the largest USL was 1.5 cm (interquartile range, 1-2 cm), and median total length of all neoplastic USLs was 2 cm (range, 1-10 cm). Patients with focal disease received a median of 2 cryoablations, whereas 4 patients with large and/or multifocal circumferential neoplasia had 6 to 12 ablations per procedure. The median procedure time was 34 minutes (range, 18-57 minutes). Treatment was completed in all patients. No major adverse events occurred. Four patients developed mild self-limited chest pain requiring narcotic analgesics immediately after the procedure. Two patients who received circumferential ablation developed a stricture responding to dilation, with no recurrence. Complete endoscopic and pathologic response was achieved in all patients at 3 months. One year follow-up biopsy specimens in 7 patients showed no USL or ESCN. All patients were disease free at last visit, with a median follow-up time of 10.7 months (interquartile range, 4-14 months). CONCLUSIONS: We report the first application of nitrous cryoballoon ablation for curative treatment of early primary or recurrent ESCN. Our initial experience suggests that efficacy is high and the safety profile is reasonable. Prospective trials are needed to optimize cryogen dosimetry and assess safety and efficacy.	esophagus
The Evolving Genomic Landscape of Barrett's Esophagus and Esophageal Adenocarcinoma.	We have recently gained unprecedented insight into genetic factors that determine risk for Barrett's esophagus (BE) and progression to esophageal adenocarcinoma (EA). Next-generation sequencing technologies have allowed us to identify somatic mutations that initiate BE and track genetic changes during development of tumors and invasive cancer. These technologies led to identification of mechanisms of tumorigenesis that challenge the current multistep model of progression to EA. Newer, cost-effective technologies create opportunities to rapidly translate the analysis of DNA into tools that can identify patients with BE at high risk for cancer, detect dysplastic lesions more reliably, and uncover mechanisms of carcinogenesis.	esophagus
New prospective 4D-CT for mitigating the effects of irregular respiratory motion.	Artifact caused by irregular respiration is a major source of error in 4D-CT imaging. We propose a new prospective 4D-CT to mitigate this source of error without new hardware, software or off-line data-processing on the GE CT scanner. We utilize the cine CT scan in the design of the new prospective 4D-CT. The cine CT scan at each position can be stopped by the operator when an irregular respiration occurs, and resumed when the respiration becomes regular. This process can be repeated at one or multiple scan positions. After the scan, a retrospective reconstruction is initiated on the CT console to reconstruct only the images corresponding to the regular respiratory cycles. The end result is a 4D-CT free of irregular respiration. To prove feasibility, we conducted a phantom and six patient studies. The artifacts associated with the irregular respiratory cycles could be removed from both the phantom and patient studies. A new prospective 4D-CT scanning and processing technique to mitigate the impact of irregular respiration in 4D-CT has been demonstrated. This technique can save radiation dose because the repeat scans are only at the scan positions where an irregular respiration occurs. Current practice is to repeat the scans at all positions. There is no cost to apply this technique because it is applicable on the GE CT scanner without new hardware, software or off-line data-processing.	esophagus
Efficacy And Toxicity Of Carboplatin/Paclitaxel Based Chemoradiation For Localized Oesophageal Cancer.	BACKGROUND: The management of Oesophageal and Gastroesophageal junction cancers is challenging. Multimodality therapy with carboplatin/paclitaxel based chemoradiation (CRT) and surgery shows improved efficacy. In this study, we wanted to establish the efficacy and safety of CRT for neoadjuvant and radical treatment of localized oesophageal cancer. METHODS: Patients with oesophageal cancer, registered between September 2013 and October 2014 were reviewed retrospectively. Toxicity and efficacy analysis in the form of radiological response rate, R0 resection rate, Progression free survival (PFS) and overall survival (OS) was performed on 102 patients who received radical carbo/pacli induction chemotherapy followed by CRT. Impact of Surgery was seen on PFS and OS. RESULTS: Males and females were 71 (51.1%) and 68 (48.9%) respectively, with squamous cell carcinoma being the predominant histology (92%). Majority of patient belonged to T3/4 and N1 stage. Grade III/IV thrombocytopenia, neutropenia, anaemia, febrile neutropenia requiring hospitalisation, non-hematologic toxicities were noted in 13 (12.8%), 18 (17.7%), 18 (17.7%), 1 (1%), 1 (1%), patients respectively. Complete Radiological response, partial response, Stable disease, progressive disease was seen in 6 (5.9%), 51 (50%), 23 (22.5%) 8 (8.7%), respectively. Resection was done in 29 (28.4%). Complete and partial pathological response were seen 19 (65.5%), 10 (34.4%), respectively. PFS at 40 and 80 weeks was 90%, 73%, respectively and OS at 80 weeks was 86%. PFS at 40 and 80 weeks was 100% and 90.5%, respectively with resection, while it was 86% and 65%, without resection (P value 0.015). OS at 40 and 80 weeks was 100% (both) with resection, while it was 96% and 79.5% weeks without resection. (p-value 0.034). CONCLUSIONS: Carbo/pacli based CRT is effective with acceptable toxicity profile in treating localised oesophageal cancer as both as Radical CRT and as a part of multimodality therapy. For definitive results, long term follow up and prospective analysis are required.	esophagus
Prevalence and significance of HMGA2 expression in oesophageal adenocarcinoma.	AIMS: Oesophageal adenocarcinoma (EAC) tumorigenesis has been linked primarily to loss-of-function mutations in tumour suppressor genes. Knowledge of specific oncogenes that drive tumour progression, and their relationship to outcomes, is limited. High mobility group AT-hook 2 (HMGA2) has been reported to be amplified in a subset of EACs, but the clinicopathological and prognostic implications of HMGA2 expression in EAC are unknown. METHODS AND RESULTS: We performed HMGA2 immunohistochemistry and fluorescence in-situ hybridization (FISH) in EAC to determine its clinicopathological and prognostic significance. Ninety-one primary EAC resections without neoadjuvant treatment were identified and immunohistochemistry for HMGA2 was performed. The presence or absence of nuclear staining was evaluated and correlated with predetermined clinicopathological parameters and patient outcomes. A selected subset of tumours was subjected to FISH to identify alterations at the HMGA2 locus. HMGA2 expression was present in 25 of 91 (27.4%) tumours. HMGA2-expressing cells were present in solid, poorly differentiated areas of the tumours at the invasive front, or as single infiltrating cells. FISH showed that three to four copies of HMGA2 are frequently present in EAC irrespective of HMGA2 protein expression and that high level HMGA2 amplification is a rare event. HMGA2 expression was associated with numerous adverse clinicopathological parameters, including higher T- and N-stage, the presence of lymphovascular invasion and with a worse recurrence-free and overall survival. CONCLUSION: Our data suggest that HMGA2 is regulated in EAC primarily through non-chromosomal-level alterations that lead to increased HMGA2 expression. HMGA2-positive EAC correlates with adverse pathological features and worse patient outcomes.	esophagus
Clinical value of integrated-signature miRNAs in esophageal cancer.	MicroRNAs (miRNAs) are crucial regulators of gene expression in tumorigenesis and are of great interest to researchers, but miRNA profiles are often inconsistent between studies. The aim of this study was to confirm candidate miRNA biomarkers for esophageal cancer from integrated-miRNA expression profiling data and TCGA (The Cancer Genome Atlas) data in tissues. Here, we identify five significant miRNAs by a comprehensive analysis in esophageal cancer, and two of them (hsa-miR-100-5p and hsa-miR-133b) show better prognoses with significant difference for both 3-year and 5-year survival. Additionally, they participate in esophageal cancer occurrence and development according to KEGG and Panther enrichment analyses. Therefore, these five miRNAs may serve as miRNA biomarkers in esophageal cancer. Analysis of differential expression for target genes of these miRNAs may also provide new therapeutic alternatives in esophageal cancer.	esophagus
Surface modification of esophageal stent materials by a polyethylenimine layer aiming at anti-cancer function.	Esophageal cancer is difficult to cure globally and possesses high mortality rate, and it is generally accepted that palliative care such as stent implantation is the main therapy method for esophageal cancer in later period. However, the restenosis caused by tumor cells and inflammatory cells seriously interferes the stent clinical application and limits its long-term services. To solve this problem, series of drug delivery stents were developed and proven rather effective in the early stage of implantation, but more serious restenosis occurred after the drug delivery was over, which endangered the patients' life. Therefore, endowing the esophageal stent continuous anti-cancer function become an ideal strategy for inhibiting the restenosis. In this contribution, the functional layer composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with series of molecular weights (MW, 1.8 × 10(3), 1 × 10(4), 2.5 × 10(4) and 7 × 10(4) Da) were fabricated onto the esophageal stent material 317L stainless steel (317L SS) surface. The surface characterization including amine quantitative, atomic force microscopy (AFM) and water contact angle measurement indicated successful preparation of the PDA/PEI layer. The Eca109 cells culture results proved that the PDA/PEI layers significantly improve Eca109 cells apoptosis and necrosis, suggesting excellent anti-cancer function. In addition, we also found that the anti-cancer function of the PDA/PEI layers was positively correlated to the immobilized PEIs' MW. All the results demonstrated the potential application of the PDA/PEI layers on the surface modification of esophageal stent for continuous anti-cancer function. It is generally accepted that the restenosis caused by tumor cells seriously interferes the esophageal stent clinical application. Thus, endowing the esophageal stent continuous anti-cancer function is the ideal strategy for inhibiting the restenosis. In this work, we fabricated functional layers composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with series of molecular weights (MW, 1.8 × 10(3), 1 × 10(4), 2.5 × 10(4) and 7 × 10(4) Da) onto the esophageal stent material 317L stainless steel (317L SS) surface to inhibit the tumor cells growth, and this function was related to the PEIs' molecular weights. The functional PDA/PEI layers were expected potentially applied for surface modification of esophageal stent materials.	esophagus
New magnifying endoscopic classification for superficial esophageal squamous cell carcinoma.	AIM: To assess the accuracy of a new magnifying endoscopy (ME) classification for predicting depth of invasion of superficial esophageal squamous cell carcinoma (SESCC). METHODS: This study included a total of 70 lesions in 69 patients with SESCC who underwent ME with narrow-band imaging (ME-NBI) before resection from August 2010 to July 2016. Accuracy of ME-NBI for predicting depth of invasion of SESCC was analyzed by using a new ME classification proposed by the Japan Esophageal Society (JES), and interobserver agreement was assessed. RESULTS: Overall accuracy of ME-NBI for estimating depth of invasion of SESCC was 78.6%. Sensitivity and specificity of type B1 for tumors limited to the epithelial layer (m1) or invading into the lamina propria (m2) were 71.4% and 100%, respectively. Sensitivity and specificity of type B2 for tumors invading into the muscularis mucosa (m3) or superficial submucosa (≤ 200 μm, sm1) were 94.4% and 73.1%, respectively, while those of type B3 for tumors invading into the deep submucosa (> 200 μm, sm2) were 75.0% and 97.8%, respectively. Interobserver agreement was excellent (κ = 0.86, 95%CI: 0.76-0.95). CONCLUSION: The recently developed JES ME classification is useful for predicting depth of invasion of SESCC, with reliable interobserver agreement.	esophagus
Hamburg-Glasgow classification: preoperative staging by combination of disseminated tumour load and systemic inflammation in oesophageal carcinoma.	BACKGROUND: The aim of this study was to establish a new preoperative staging classification and evaluate its comparability to the post-operative tumour stage, lymph node invasion and metastasis (TNM) classification. To date, adequate, preoperative staging in patients with oesophageal carcinoma (EC) is still missing but urgently needed. Systemic inflammation and disseminated tumour load have a pivotal role in recurrence and oncological outcome. To improve the clinical staging, we merged the Glasgow Prognostic Score (GPS) and disseminated tumour cells (DTC) into a new sufficient preoperative staging classification, the Hamburg-Glasgow classification (HGC). METHODS: In this prospective, single-centre study, 326 patients following curative oesophagectomy were included. From all patients preoperative bone marrow was aspirated from the iliac crest to detect DTCs by immunostaining with the pan-keratin antibody A45-B/B3. HGC was subdefined into four prognostic groups on the basis of C-reactive protein (CRP), albumin and DTC. The three prognostic groups of the GPS were supplemented by DTC detection status. Results were correlated with clinicopathological parameters and clinical outcome. RESULTS: Increasing HGC significantly correlated with lymph node invasion (P=0.022), post-operative pathohistological TNM staging (P=0.001) and tumour recurrence (P=0.001). The four HGC prognostic groups displayed a gradual decrease in overall as well as disease-free survival (P<0.001, each). Hamburg-Glasgow classification was a strong, significant independent predictor of overall survival and disease-free survival (P<0.001, both) in multivariate analysis. CONCLUSIONS: Hamburg-Glasgow classification seems to be a promising preoperative additive staging classification for accurate and simple outcome stratification.	esophagus
Effect of Esophageal Cancer Surgeon Volume on Management and Mortality From Emergency Upper Gastrointestinal Conditions: Population-based Cohort Study.	OBJECTIVE: To study the influence of esophageal cancer surgeon volume upon mortality from upper gastrointestinal emergencies. BACKGROUND: Volume-outcome relationships led to the centralization of esophageal cancer surgery. METHODS: Hospital Episode Statistics data were used to identify patients admitted to hospitals within England (1997-2012). The influence of esophageal high-volume (HV) cancer surgeon status (≥5 resections per year) upon 30-day and 90-day mortality from esophageal perforation (EP), paraesophageal hernia causing obstruction or gangrene (PEH) and perforated peptic ulcer (PPU) was analyzed, independent of HV esophageal cancer center status and patient and disease-specific confounding factors. RESULTS: A total of 3707, 12,411, and 57,164 patients with EP, PEH, and PPU, respectively, were included. The observed 90-day mortality was 36.5%, 11.5%, and 29.0% for EP, PEH, and PPU, respectively.Management by HV cancer surgeon was independently associated with significant reductions in 30-day and 90-day mortality from EP (odds ratio, OR 0.51, 95% confidence interval, CI, 0.40-0.66), PEH (OR=0.70, 95% CI 0.53-0.91), and PPU (OR=0.85, 95% CI 0.7-0.95). Subset analysis of those patients receiving primary surgery as treatment showed no change in mortality when performed by HV cancer surgeons.However HV cancer surgeons performed surgery as primary treatment more commonly for EP (OR=2.38, 95% CI 1.87-3.04) and PEH (OR=2.12, 95% CI 1.79-2.51). Furthermore surgery was independently associated with reduced mortality for all 3 conditions. CONCLUSION: The complex elective workload of HV esophageal cancer surgeons appears to lower the threshold for surgical intervention in specific upper gastrointestinal emergencies such as EP and PEH, which in turn reduces mortality.	esophagus
Lymph node station ratio: Revised nodal category for resected esophageal squamous cell carcinoma patients.	OBJECTIVES: The objective of this study was to evaluate a revised nodal category based on the value of the lymph node (LN) station ratio (SR, metastatic LN stations/examined LN stations) in esophageal squamous cell carcinoma (ESCC) patients. METHODS: Data were obtained from 857 ESCC patients who underwent primary radical esophagectomy. Prognostic performance was evaluated using the Harrell concordance index (C-index), Akaike information criterion (AIC), and likelihood ratio χ(2) test (LR χ(2) test). RESULTS: Each subgroup among the SR categories demonstrated discriminatory results, whereas no significant survival difference was observed between the N2 versus N3 classifications under the AJCC pN system. Using the AJCC TNM staging system, the survival curves separated between stages IIIA-IIIB and IIIB-IVA. However, when the T-SR-M scheme category was applied, the survival curves between stages IIA-IIB, IIIA-IIIB, and IIIB-IVA were significantly different. Furthermore, both the SR category and the T-SR-M staging system showed superior performance with higher C-index and LR χ(2) test values and lower AIC values compared with the pN category and TNM staging system, respectively. CONCLUSIONS: Following radical esophagectomy, the SR category demonstrated superior prognostic ability relative to the AJCC pN category in ESCC patients.	esophagus