crossing96/oncoscreening huggingface dataset:
Cancer-associated fibroblasts (CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma.	Lymph node metastasis is a pathognomonic feature of spreading tumors, and overcoming metastasis is a challenge in attaining more favorable clinical outcomes. Esophageal cancer is an aggressive tumor for which lymph node metastasis is a strong poor prognostic factor, and the tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in particular, has been implicated in esophageal cancer progression. CAFs play a central role in the TME and have been reported to provide suitable conditions for the progression of esophageal cancer, similar to their role in other malignancies. However, little is known concerning the relevance of CAFs to the lymph node metastasis of esophageal cancer. Here, we used clinical samples of esophageal cancer to reveal that CAFs promote lymph node metastasis and subsequently verified the intercellular relationships in vitro and in vivo using an orthotopic metastatic mouse model. In the analysis of clinical samples, FAP(+) CAFs were strongly associated with lymph node metastasis rather than with other prognostic factors. Furthermore, CAFs affected the ability of esophageal cancer cells to acquire metastatic phenotypes in vitro; this finding was confirmed by data from an in vivo orthotopic metastatic mouse model showing that the number of lymph node metastases increased upon injection of cocultured cancer cells and CAFs. In summary, we verified in vitro and in vivo that the accumulation of CAFs enhances the lymph node metastasis of ESCC. Our data suggest that CAF targeted therapy can reduce lymph node metastasis and improve the prognosis of patients with esophageal cancer in the future.	esophagus
Activation of PAR4 Upregulates p16 through Inhibition of DNMT1 and HDAC2 Expression via MAPK Signals in Esophageal Squamous Cell Carcinoma Cells.	A previous study showed that a downexpression of protease-activated receptor 4 (PAR4) is associated with the development of esophageal squamous cell carcinoma (ESCC). In this study, we explored the relationship between PAR4 activation and the expression of p16, and elucidated the underlying mechanisms in PAR4 inducing the tumor suppressor role in ESCC. ESCC cell lines (EC109 and TE-1) were treated with PAR4-activating peptide (PAR4-AP). Immunohistochemistry for DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) was performed in 26 cases of ESCC tissues. We found that DNMT1 and HDAC2 immunoreactivities in ESCC were significantly higher than those in adjacent noncancerous tissues. PAR4 activation could suppress DNMT1 and HDAC2, as well as increase p16 expressions, whereas silencing PAR4 dramatically increased HDAC2 and DNMT1, as well as reduced p16 expressions. Importantly, the chromatin immunoprecipitation-PCR (ChIP-PCR) data indicated that treatment of ESCC cells with PAR4-AP remarkably suppressed DNMT1 and HDAC2 enrichments on the p16 promoter. Furthermore, we demonstrated that activation of PAR4 resulted in an increase of p38/ERK phosphorylation and activators for p38/ERK enhanced the effect of PAR4 activation on HDAC2, DNMT1, and p16 expressions, whereas p38/ERK inhibitors reversed these effects. Moreover, we found that activation of PAR4 in ESCC cells significantly inhibited cell proliferation and induced apoptosis. These findings suggest that PAR4 plays a potential tumor suppressor role in ESCC cells and represents a potential therapeutic target of this disease.	esophagus
Influence of Patients' Age in the Utilization of Esophagectomy for Esophageal Adenocarcinoma.	BACKGROUND: The indication of surgical resection in esophageal cancer is often conditioned by patient's age. We aimed to assess the trends in utilization of surgical treatment for esophageal adenocarcinoma (EAC) in the United States, stratified by age groups. METHODS: We performed a retrospective analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results program registry for the period 2004-2014. Adult patients (aged ≥18 years) diagnosed with EAC were eligible for inclusion. The yearly incidence of esophagectomy, stratified by age groups (18-49, 50-70, and >70 years old), was calculated using Poisson regression. Weighted log-binomial regression was used to compare the proportion of patients undergoing esophagectomy, within each age group. Inverse probability of treatment weights were used to account for potential confounders. RESULTS: A total of 21,301 patients were included. During the study period, the rate of esophagectomy decreased from 34.1% to 28.2% (P = .40) in patients between 18 and 49 years old, from 38.6% to 33.3% (P = .06) in patients between 50 and 70 years old, and from 21.4% to 16.9% (P = .04) in patients older than 70 years. After accounting for patient and cancer characteristics, patients older than 70 years were 50% less likely to undergo esophagectomy compared with both patients between 18 and 49 years old (risk ratio [RR] 0.51, 95% confidence interval [CI] 0.45-0.57, P < .0001) and patients between 50 and 70 years old (RR 0.53, 95% CI 0.50-0.56, P < .0001). CONCLUSION: Surgical resection is scarcely used in patients older than 70 years in the United States. Further investigation of surgical outcomes in elderly patients is warranted to determine if surgical treatment is underutilized in a large proportion of EAC patients.	esophagus
2017 David Sun Lecture: Screening and Surveillance of Barrett's Esophagus: Where Are We Now and What Does the Future Hold?	Barrett's esophagus and esophageal adenocarcinoma continue to present considerable management challenges in the Western world. Despite our best efforts to date, the prognosis of advanced esophageal adenocarcinoma remains poor and far too many individuals with esophageal adenocarcinoma have not had a prior endoscopy to detect Barrett's esophagus. As such, current strategies of screening for Barrett's esophagus and subsequent surveillance need to be further optimized. Screening today is limited to high definition white light endoscopy in high-risk patient populations and as such has multiple limitations. However, a variety of exciting new techniques including risk prediction tools, tethered capsule endomicroscopy, a cytology sponge, breath testing for exhaled volatile organic compounds, and assessment of the oral microbiome are now under study in an effort to develop less expensive population-based screening methods. Similarly, endoscopic surveillance, as currently practiced has a variety of limitations. Inexpensive readily available adjuncts are already available to optimize surveillance including increased inspection time in an effort to detect mucosal or vascular abnormalities, special attention to the right hemisphere of the esophagus, and utilization of narrow band imaging or other electronic chromoendoscopy techniques. To improve endoscopic surveillance, a variety of new paradigms are under study including wide area trans-epithelial sampling, advanced endoscopic imaging, molecular imaging, clinical risk stratification and utilization of biomarkers of increased risk. However, progress will be challenging due to the complexity of esophageal cancer biology and the rarity of progression to cancer among patients with nondysplastic Barrett's epithelium.	esophagus
CFTR inhibits the invasion and growth of esophageal cancer cells by inhibiting the expression of NF-κB.	Our study aimed to explore the function of cystic fibrosis transmembrane conductance regulator (CFTR) in esophageal cancer. Twenty patients with esophageal squamous cell carcinoma (ESCC) and 20 patients with esophageal adenocarcinoma (EA) were enrolled in this study. The levels of CFTR and NF-κB in tumor tissues and adjacent normal tissues were detected, respectively. The expression of CFTR were detected by qRT-PCR and Western blot in normal esophageal cell line, esophagus squamous cell, carcinoma cell lines, and EA cell lines, respectively. Effects of CFTR silencing and overexpression on NF-κB protein expression were detected by Western blot. Transwell assay was performed to detect cell invasion. Mouse tumor model was established and the effect of CFTR inhibitor on tumor growth was examined. The expression of CFTR was downregulated in tumor tissues and cancer cell lines. CFTR silencing promoted the expression of NF-κB-p65 and NF-κB-p50, and the results of CFTR overexpression were reversed. In addition, CFTR silencing promoted the invasion of cancer cells and tumor growth in mice. Besides that, NF-κB inhibitor reduced the enhancing effects of CFTR silencing on esophageal cell invasion. We conclude that CFTR inhibits the growth and migration of esophageal cancer cells by downregulating of the NF-κB protein expression.	esophagus
Analysis of the Effect of Early Versus Conventional Nasogastric Tube Removal on Postoperative Complications After Transthoracic Esophagectomy: A Single-Center, Randomized Controlled Trial.	BACKGROUND: Although esophagectomy is the only curative option for esophageal cancer, the associated invasiveness is high. Nasogastric (NG) tube use may prevent complications; however, its utility remains unclear, and the decompression period depends on the doctor. This study aimed to reveal the effect of conventional versus early NG tube removal on postoperative complications after esophagectomy. METHODS: This single-center prospective randomized controlled clinical trial enrolled patients aged 20-80 years with histologically proven primary esophageal squamous cell carcinoma. Eighty patients admitted for transthoracic first-stage esophagectomy reconstructed with gastric conduit were randomly assigned (1:1) to the conventional and early NG tube removal groups. In the conventional NG tube removal group, the tube was removed on postoperative day (POD) 7; in the other, it was removed on POD 1. The occurrence rate of major complications, length of postoperative hospital stay, and NG tube reinsertion rate were compared between the groups. RESULTS: The incidence of postoperative major complications such as pneumonia, anastomotic leakage, recurrent nerve palsy and gastrointestinal bleeding, and the NG tube reinsertion rate was not different between the groups. However, recurrent nerve palsy was more commonly observed in the conventional removal group; this difference was not significant. In terms of postoperative pneumonia, tumor location and field of lymph node dissection were significant risk factors. CONCLUSION: Although early NG tube removal did not reduce the rate of postoperative pneumonia, it could be performed safely. Hence, the NG tube can be removed earlier than conventional methods.	esophagus
Health-related quality of life of esophageal cancer patients in daily life after treatment: A multicenter cross-sectional study in China.	BACKGROUND: The improvement of diagnostic and therapeutic techniques has prolonged the survival time of patients with esophageal cancer. Little is known, however, about their health-related quality of life (HRQoL) in daily life after treatment. METHODS: Esophageal cancer patients who had been discharged from hospitals more than one year and healthy controls identified by screening were recruited from seven study centers covering eastern, central, and western regions of China. Patients were categorized into severe dysplasia/carcinoma in situ and stages I, II, III, and IV cancer, respectively. The EQ-5D was employed to assess HRQoL. Multivariate regression analyses were conducted. RESULTS: A total of 1456 patients and 2179 controls were recruited. After adjusting for potential confounding factors, the likelihood of reporting problems in the five dimensions of patients was 3.8 to 23.1 times higher than controls, whilst the mean EQ-5D utility score was 0.311 (95% CI, 0.276-0.346) lower than controls. The mean utility scores of each patient subgroup were 0.158, 0.289, 0.303, 0.296, and 0.505 (95% CIs: 0.108-0.208, 0.243-0.336, 0.261-0.346, 0.244-0.347, and 0.437-0.573) lower than controls, respectively. Patients had the greatest impairment in the self-care dimension compared with controls, followed by the usual activities dimension. Therapeutic regimen, duration of illness, other chronic disease status, age, and marital status also had significant impact on different aspects of HRQoL in patients. CONCLUSIONS: Esophageal cancer significantly impaired patients' HRQoL in daily life after treatment. Advanced cancer stages were associated with larger decrements on health state utility. Utility scores reported here can facilitate further cost-utility analyses.	esophagus
Spleen Dose-Volume Parameters as a Predictor of Treatment-related Lymphopenia During Definitive Chemoradiotherapy for Esophageal Cancer.	AIM: Our study sought to identify dosimetric predictors of treatment-related lymphopenia during chemoradiotherapy for esophageal cancer. MATERIALS AND METHODS: Patients with esophageal cancer who had received definitive chemoradiotherapy at our Institution were retrospectively assessed. The absolute volume of the spleen, body, and bone marrow that had received 5, 10, 20, and 30 Gy and the mean splenic dose were recorded. RESULTS: Multivariate linear regression analysis revealed that docetaxel use and spleen dose-volume parameters (V5, V10, V20, V30, and mean splenic dose) were significant independent factors negatively influencing the absolute lymphocyte count at nadir. An increase of 1 Gy in mean splenic dose predicted a 2.9% decrease in nadir absolute lymphocyte count. Univariable logistic regression analysis showed that the mean splenic dose was a significant predictor of grade 4 lymphopenia. None of the body or bone marrow dose-volume parameters significantly predicted lymphopenia. CONCLUSION: Higher spleen dose-volume parameters were associated with severe lymphopenia during chemoradiotherapy.	esophagus
Analysis of Circulating Tumor DNA and Clinical Correlates in Patients with Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma.	PURPOSE: Esophageal, gastroesophageal junction, and gastric adenocarcinoma (herein gastroesophageal adenocarcinomas) are associated with poor prognosis and limited systemic treatment options. To further understand the genomic landscape of gastroesophageal cancers and its clinical correlations, circulating tumor DNA (ctDNA) from patients' plasma was evaluated using next-generation sequencing (NGS). EXPERIMENTAL DESIGN: We analyzed genomic alterations of 55 patients (mostly advanced disease; 9, surgically resectable) with gastroesophageal adenocarcinomas using clinical-grade NGS performed on plasma-derived ctDNA (54-73 gene panel). The test detects single-nucleotide variants, as well as copy number amplifications, fusions, and indels in selected genes. RESULTS: Seventy-six percent of patients (42/55) had ≥1 genomic alteration [including variants of unknown significance (VUS)] and 69.1% (38/55) had ≥1 characterized alteration (excluding VUSs). The median number of alterations per patient was 2 (range, 0-15). TP53 (50.9%, 28/55), PIK3CA (16.4%, 9/55), ERBB2 (14.5%, 8/55), and KRAS (14.5%, 8/55) genes were most frequently affected characterized alterations. Thirty-one patients also had tissue NGS. Concordance between tissue and ctDNA ranged from 61.3% (TP53 alterations) to 87.1% (KRAS alterations). ERBB2 alterations were significantly associated with poor overall survival (HR, 14.06; 95% confidence interval, 2.44-81.03; P = 0.003 multivariate analysis). Among patients with ≥1 alteration, no 2 patients had identical molecular portfolios. All patients with ≥1 characterized alteration had theoretically targetable alterations by an FDA-approved agent (on- or off-label). Illustrative case treated with cognate agent is presented. CONCLUSIONS: Evaluation of ctDNA by NGS among patients with gastroesophageal adenocarcinoma is feasible. Patients harbored heterogeneous patterns of genomics, with most having alterations that are potentially pharmacologically tractable.	esophagus
Quantifying postoperative mobilisation following oesophagectomy.	OBJECTIVE: Early mobilisation is in integral component of postoperative recovery following complex surgical procedures such as oesophageal cancer resections, however evidence to guide early mobilisation protocols in critical care settings is limited. Furthermore, little is known about actual mobilisation levels postoperatively. This study quantified postoperative mobilisation post- oesophagectomy and investigated barriers to mobility. DESIGN: Prospective observational study. SETTING: Postoperative critical care setting in a tertiary care referral centre for oesophagectomy. PARTICIPANTS: Thirty participants (mean age 65 (SD 7) years, n=19 males) scheduled for oesophagectomy. MAIN OUTCOME MEASURES: The primary outcome, postoperative physical activity, was measured objectively using the Actigraph GT3X+. Medical records were examined for a range of outcomes including medical status, pain scores and physiotherapy comments to identify factors which may have influenced mobility. RESULTS: During postoperative day (POD) 1-5, participants spent the majority of time (>96%) sedentary. Participation in light intensity activity was low but did increase daily from a median of 12 (IQR 19) minutes/day on POD1 to a median of 53 (IQR 73.25) minutes/day on POD5 p<0.001), with a corresponding increase in daily step count. Haemodynamic instability was the most common reason reported by physiotherapists for either not attempting mobility or limiting postoperative mobilisation levels. CONCLUSIONS: These data demonstrate that despite daily physiotherapy, there are multiple challenges to postoperative mobilisation. Haemodynamic instability, likely related to thoracic epidurals, was the key limitation to early mobilisation. Goal-directed mobilisation in collaboration with the multidisciplinary team may play a considerable role in overcoming modifiable barriers to postoperative mobilisation.	esophagus
Expression analysis of cyclooxygenase-2 in patients suffering from esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is one of the aggressive malignancies and mechanisms underlying its pathogenesis remain unclear. Cyclooxygenase-2 (COX-2) enzyme system plays a crucial role in many gastrointestinal malignancies and is an important regulator of cell growth, proliferation, apoptosis, differentiation and transformation. More precise outcome of COX-2 in ESCC is less investigated. In this study we investigated the risk factors of ESCC and expression of COX-2 in Carcinoma in situ (CIS) and ESCC compared to normal esophageal mucosa. ESCC relationship to clinico-pathological parameters using immunohistochemistry was also part of this investigation. Current study was conducted in the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan. A total of 69 diagnosed patients of ESCC, both Pakistanis and Afghans were enrolled. Various risk factors associated with ESCC were recorded. Mean age at the time of diagnosis was 55 years. Out of 69 patients of ESCC 46 (67%) were users of dipping tobacco (Naswar). Expression of COX-2 was determined in normal esophageal mucosa, CIS and invasive ESCC using Immunohistochemistry (IHC). Differences of mean were computed using ANOVA followed by applying Post Hoc test. Patients were categorized as positive with high expression or negative with low to nil expression. ANOVA showed large differences in expression of COX-2 in normal healthy mucosa compared with CIS and ESCC with the mean difference of -9.529 and -7.370 respectively, p-value being <.05 at 95% confidence interval (CI). No significant difference was noticed in the expression of COX-2 in CIS compared with ESCC with p-value >.05 at 95% CI. Our complete cohort (23-85 years) showed statistically significant difference in the expression of COX-2 gene in ESCC and CIS tissue samples compared with normal healthy mucosa. Results of this study indicate that over-expression of COX-2 is positively associated with ESCC.	esophagus
Medical and Surgical Complications and Health-related Quality of Life After Esophageal Cancer Surgery.	OBJECTIVE: To evaluate the impact of postoperative medical and surgical complications on health-related quality of life (HRQOL) in esophageal cancer. BACKGROUND: Complications after esophageal surgery negatively affect HRQOL, but it is unclear whether medical and surgical complications differ in effects. METHODS: This Swedish population-based, nationwide, and prospective cohort study enrolled 616 patients undergoing esophageal cancer surgery during 2001 to 2005, with 10 years of follow-up. The exposure was the occurrence of the predefined postoperative medical or surgical technical complications. The study outcome was HRQOL, evaluated by European Organisation for Research and Treatment of Cancer questionnaires at 6 months, and 3, 5, and 10 years after surgery. Linear mixed models, adjusted for confounders and complications, provided mean score differences (MDs) and 95% confidence intervals (CIs) for each HRQOL scale and item. RESULTS: Of the 616 patients, 217 (35%) had medical and 163 (26%) had surgical postoperative complications. In patients with medical complications, HRQOL was generally worse at all time points, with worse global quality of life (QOL) (MD -10, 95% CI -18 to -2) and dyspnea (MD 16, 95% CI 5-27) from 3 years onwards, compared with those without. Patients with surgical complications had worse HRQOL outcomes up to 5 years after surgery, for example, dyspnea at 6 months (MD 11, 95% CI 4-19) and global QOL at 3 years (MD -13, 95% CI -22 to -5), than those without. CONCLUSION: Medical complications are associated with long-lasting impairments and worsening HRQOL, whereas the negative effects of surgical complications on HRQOL seem to minimize 5 years postsurgery.	esophagus
Surgeon Volume and Surgeon Age in Relation to Proficiency Gain Curves for Prognosis Following Surgery for Esophageal Cancer.	BACKGROUND: Surgery proficiency gain curves must be shortened to reduce patient harm during esophagectomy learning. OBJECTIVE: This study aimed to test whether surgeon volume and surgeon age influenced the length of period of surgical proficiency gain. METHODS: This population-based cohort study included 1384 patients with esophageal cancer who underwent esophagectomy by any of the 36 highest-volume surgeons in Sweden between 1987 and 2010, with follow-up until 2016. Annual surgeon volume was dichotomized by the median values into 'higher-volume surgeons' (≥ 4 cases per year) and 'lower-volume surgeons' (< 4 cases per year), and surgeon age at the start of practicing esophagectomies into 'younger surgeons' (aged < 45 years) and 'older surgeons' (aged ≥ 45 years). Proficiency gain curves were constructed using risk-adjusted cumulative sum analysis for 1- to 5-year mortality (main outcome) and secondary outcomes (presented below). The results were adjusted for all established prognostic factors. RESULTS: For 1- to 5-year mortality, the change point was at 14 cases among 'higher-volume surgeons', while 'lower-volume surgeons' had a later change point at 31 cases. The corresponding change points were at 13 cases among 'younger surgeons' and at 48 cases among 'older surgeons'. Similar patterns of differences in the proficiency gain curves were seen for the secondary outcomes of 30-day mortality and resection margin status (tumor involvement). CONCLUSION: Higher-volume- and younger surgeons seem to have a substantially shorter period of proficiency gain for long-term mortality and other outcomes following surgery for esophageal cancer. This indicates a value of intensified training of younger surgeons for these complex operations.	esophagus