crossing96/oncoscreening huggingface dataset:
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone induces retinoic acid receptor β hypermethylation through DNA methyltransferase 1 accumulation in esophageal squamous epithelial cells.	Overexpression of DNA methyltransferase 1 (DNMT1) has been detected in many cancers. Tobacco exposure is known to induce genetic and epigenetic changes in the pathogenesis of malignancy. 4-(Methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen present in tobacco smoke; however the detailed molecular mechanism of how NNK induces esophageal carcinogenesis is still unclear. We found that DNMT1 was overexpressed in ESCC tissues compared with paired non-cancerous tissues, the overexpression being correlated with smoking status and low expression of RARβ. The latter could be upregulated by NNK treatment in Het-1A cells, and the increased DNMT1 expression level reflected promoter hypermethylation and downregulation of retinoic acid receptor β (RARβ). RNA interference mediated knockdown of DNMT1 resulted in promoter demethylation and upregulation of RARβ in KYSE30 and TE-1 cells. 3-(4,5-Dimethyl-thiazol-2yl)- 2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis demonstrated that NNK treatment in Het- 1A cells could enhance cell proliferation and inhibit cell apoptosis in a dose-dependent manner. In conclusion, DNMT1 overexpression is correlated with smoking status and low expression of RARβ in esophageal SCC patients. NNK could induce RARβ promoter hypermethylation through upregulation of DNMT1 in esophageal squamous epithelial cells, finally leading to enhancement of cell proliferation and inhibition of apoptosis.	esophagus
Recombinant human endostatin combined with definitive chemoradiotherapy as primary treatment for patients with unresectable but without systemic metastatic squamous cell carcinoma of the oesophagus.	OBJECTIVE: The objective of this study was to review the outcomes of recombinant human endostatin combined with chemoradiotherapy (CRT) as primary treatment for patients with unresectable but without systemic metastatic squamous cell carcinoma (SCC) of the oesophagus. METHODS: A total of 38 patients with unresectable but without systemic metastatic SCC of the oesophagus (T(4) or stage IVA) were retrospectively studied. 18 patients were treated with recombinant human endostatin combined with 5-fluorouracil (5-FU)/cisplatin (CDDP)-based CRT and 20 were treated with 5-FU/CDDP-based CRT alone. Short- and long-term effects including initial treatment response, survival and treatment-related complications were assessed with a median follow-up period of 36.1 months. RESULTS: CRT combined with endostatin resulted in a marked improvement in complete response rates (44.4% vs 30% in the CRT-alone group), and an increase in the 1-year and 3-year overall survival rates (72% vs 50.0% and 32% vs 22.0%, respectively), while the median time to progression was extended to 11.3 months in the combination group vs 8.1 months in the CRT-alone group. There were no treatment-related toxicities that could be attributed specifically to the endostatin, and the toxicities observed across the two groups are probably due to the CRT itself. CONCLUSIONS: The short- and long-term effects of CRT combined with endostatin were an improvement over that of CRT alone in this retrospective cohort study. This combined treatment modality may be a promising treatment modality for the patients with unresectable but without systemic metastatic oesophageal cancer. Further prospective randomised control studies are needed to confirm this finding.	esophagus
Acquired hemophilia A caused by factor VIII inhibitors: report of a case.	We report a case of acquired hemophilia A (AHA) after esophageal resection. The patient was an 80-year-old woman whose preoperative activated partial-thromboplastin time (APTT) was well within the normal range, at 34.9 s. She underwent thoracic esophagectomy and gastric pull-up for superficial esophageal cancer (operative time, 315 min; intraoperative blood loss, 245 ml). Intrathoracic and subcutaneous bleeding occurred spontaneously on postoperative day (POD) 39. The APTT was prolonged, at 140 s, and factor VIII inhibitor was 36 Bethesda U/ml. Treatment with recombinant activated factor VII, prednisolone, and cyclophosphamide resulted in remission within 2 months. This case supports an association between surgery and the triggering of factor VIII inhibitors. The diagnosis of AHA requires clinical acumen and must be considered in any patient with bleeding and a prolonged APTT.	esophagus
Long-term survival outcomes after definitive chemoradiation versus surgery in patients with resectable squamous carcinoma of the esophagus: results from a randomized controlled trial.	BACKGROUND: The aim of this study was to report on the 5-year survival outcomes of patients with resectable esophageal carcinoma who were treated by definitive chemoradiotherapy (CRT) or standard esophagectomy. PATIENTS AND METHODS: Between July 2000 and December 2004, 81 patients with resectable squamous cell carcinoma of the mid- or lower thoracic esophagus were randomized to receive esophagectomy or definitive CRT. The primary outcome was the overall survival and secondary outcomes included disease-free survival, morbidities and mortalities. RESULTS: Forty-five patients received esophagectomy and 36 patients were treated by definitive CRT. The overall 5-year survival favors CRT but the difference did not reach statistical significance (surgery 29.4% and CRT 50%, P=0.147). A trend to improved 5-year survival was observed for patients suffering from node-positive disease (P=0.061). The 5-year disease-free survival also showed a trend to significance favoring CRT (P=0.068), particularly for patients suffering from node-positive disease (P=0.017). Both the stage of the disease and albumin level were significant predictors to mortality and disease-free survival. CONCLUSIONS: Definitive CRT for squamous esophageal carcinoma resulted in comparable long-term survival to surgery. Further large-scale studies would be required to further investigate the role of CRT in node-positive patients. Clinicaltrials.gov identifier: NCT01032967.	esophagus
Gastric motor activity in gastric pull-up esophagectomized patients with and without reflux symptoms.	BACKGROUND: Patients frequently experience reflux symptoms of heartburn and regurgitation after a gastric pull-up esophagectomy. The pathogenesis of reflux symptoms is not fully understood. The gastrointestinal tract exhibits a temporally coordinated cyclic motor pattern, termed interdigestive migrating motor contraction, during the interdigestive state. Phase III of interdigestive migrating motor contraction is important in cleaning indigestible solids and basal secretions. Impairment of phase III may result in reflux symptoms of heartburn and regurgitation. The present study evaluated whether gastropyloroduodenal motility after gastric pull-up esophagectomy influences the pathogenesis of reflux symptoms. METHODS: Gastropyloroduodenal motility was recorded by manometry in 20 patients after a gastric pull-up esophagectomy. Esophagectomized patients were questioned about the presence of heartburn or regurgitation, or both. RESULTS: Of 20 patients, 8 (40%) were considered the symptomatic group. Phase III, in which contractions originating from the antrum migrate to the pylorus and then move to the duodenum, was observed in only 1 of 8 patients. In the asymptomatic group, phase III was observed in 8 of 12 patients. A significant correlation was found between the presence of reflux symptoms and the paucity of phase III activity (p=0.02). CONCLUSIONS: The presence of reflux symptoms after gastric pull-up esophagectomy is significantly associated with the paucity of gastric phase III. Gastric motor activity is important in the occurrence of reflux symptoms.	esophagus
Attributable causes of esophageal cancer incidence and mortality in China.	BACKGROUND: To estimate the contribution of tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake to esophageal cancer mortality and incidence in China. METHODOLOGY/PRINCIPAL FINDINGS: We calculated the proportion of esophageal cancer attributable to four known modifiable risk factors [population attributable fraction (PAF)]. Exposure data was taken from meta-analyses and large-scale national surveys of representative samples of the Chinese population. Data on relative risks were also from meta-analyses and large-scale prospective studies. Esophageal cancer mortality and incidence came from the 3(rd) national death cause survey and population-based cancer registries in China. We estimated that 87,065 esophageal cancer deaths (men 67,686; women: 19,379) and 108,206 cases (men: 83,968, women: 24,238) were attributable to tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake in China in 2005. About 17.9% of esophageal cancer deaths among men and 1.9% among women were attributable to tobacco smoking. About 15.2% of esophageal cancer deaths in men and 1.3% in women were caused by alcohol drinking. Low vegetable intake was responsible for 4.3% esophageal cancer deaths in men and 4.1% in women. The fraction of esophageal cancer deaths attributable to low fruit intake was 27.1% in men and 28.0% in women. Overall, 46% of esophageal cancers (51% in men and 33% in women) were attributable to these four modifiable risk factors. CONCLUSIONS/SIGNIFICANCE: Tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake were responsible for 46% of esophageal cancer mortality and incidence in China in 2005. These findings provide useful data for developing guidelines for esophageal cancer prevention and control in China.	esophagus
Increase of epidermal growth factor receptor expression in progression of GERD, Barrett, and adenocarcinoma of esophagus.	INTRODUCTION: Gastroesophageal reflux disease (GERD) is a pathology with a wide range of clinical and endoscopic manifestations. Epidermal growth factor receptor (EGFR), found in the epithelium of the digestive tract, plays an important role in epithelial repair and shows increased expression in different neoplasms, including esophageal tumors. OBJECTIVES: The purpose of this study was to evaluate EGFR expression using immunohistochemistry in esophageal biopsies obtained from patients with GERD, Barrett's esophagus, and adenocarcinoma of the esophagus. METHODS: EGFR expression was immunohistochemically determined in biopsies from 194 patients with symptoms suggestive of GERD or adenocarcinoma of the esophagus, seen at two Brazilian university hospitals between January 2003 and December 2008. Based on histopathological analysis, patients were divided into three groups: GERD, Barrett's esophagus and adenocarcinoma of the esophagus. EGFR expression was considered positive when staining was detected in the membrane. RESULTS: Mean age was 55.25 years (range 30-90). Patients with GERD (n = 127) accounted for 65.5% of the sample, compared with 12.4% (n = 24) of patients with Barrett's esophagus and 22.2% (n = 43) of patients with esophageal adenocarcinoma. Immunohistochemical analysis was positive for EGFR in 19.1% of the patients (37/194), divided as follows: 8.7% (11/127) in the GERD group, 25% (6/24) in the Barrett's esophagus group, and 46.5% (20/43) in the esophageal adenocarcinoma group. Statistical analysis revealed significant differences between the three groups (p = 0.0001). CONCLUSIONS: GERD patients showed lower levels of EGFR expression than patients with Barrett's esophagus or patients with adenocarcinoma of the esophagus, suggesting a direct relationship between EGFR expression and disease progression.	esophagus
Fuzzy logic-based prognostic score for outcome prediction in esophageal cancer.	Given the poor prognosis of esophageal cancer and the invasiveness of combined modality treatment, improved prognostic scoring systems are needed. We developed a fuzzy logic-based system to improve the predictive performance of a risk score based on the serum concentrations of C-reactive protein (CRP) and albumin in a cohort of 271 patients with esophageal cancer before radiotherapy. Univariate and multivariate survival analyses were employed to validate the independent prognostic value of the fuzzy risk score. To further compare the predictive performance of the fuzzy risk score with other prognostic scoring systems, time-dependent receiver operating characteristic curve (ROC) analysis was used. Application of fuzzy logic to the serum values of CRP and albumin increased predictive performance for 1-year overall survival (AUC=0.773) compared with that of a single marker (AUC=0.743 and 0.700 for CRP and albumin, respectively), where the AUC denotes the area under curve. This fuzzy logic-based approach also performed consistently better than the Glasgow Prognostic Score (GPS) (AUC=0.745). Thus, application of fuzzy logic to the analysis of serum markers can more accurately predict the outcome for patients with esophageal cancer.	esophagus
Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma.	BACKGROUND: Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. CASE PRESENTATION: A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. CONCLUSION: We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.	esophagus
Quantification of tumour and circulating vascular endothelial growth factor (VEGF) in patients with oesophagogastric cancer: a long-term follow-up study.	Vascular endothelial growth factor (VEGF) is an angiogenic cytokine that regulates tumour angiogenesis. The prognostic significance of VEGF expression remains incompletely investigated for patients with oesophagogastric cancer. This study assesses the significance of tumour VEGF (T-VEGF) and circulating VEGF (C-VEGF) expression in a 10-year follow-up of patients with oesophagogastric cancer. Patients undergoing surgical resection were prospectively recruited between February 1999 and August 2000. Circulating VEGF, derived both from plasma (P-VEGF) and serum (S-VEGF), and T-VEGF were assessed using a commercial enzyme-linked immunosorbent assay (ELISA). As platelet count may contribute to C-VEGF, pre-operative platelet levels were also recorded to exclude a confounding effect. Patients were followed up over a 10-year period using the Northern Ireland Cancer Registry. Sixty-one patients were recruited (men=45) with a mean age of 65.7 years. The 10-year survival was 19.7% (n=12) with a median follow-up of 808 days (inter-quartile range [IQR]: 349.5-2358.5). Union for International Cancer Control (UICC) tumour staging was Stage I=9 (14.8%), Stage II=15 (24.6%), Stage III=33 (54.1%) and Stage IV=4 (6.6%). The only significant relationship between clinicopathological features and the study variables was for S-VEGF, which was elevated in patients with advanced T-stage (P = 0.05). Circulating VEGF did not correlate with platelet count. Although a trend towards decreased survival was observed for patients who had positive lymph nodes (P = 0.08) and advanced UICC stage (P = 0.09) on univariate analysis, only lymphovascular invasion significantly predicted poor prognosis in this cohort (P = 0.05). Therefore, ELISA quantification of circulatory or tumour VEGF does not appear to be a significant predictor of mortality in patients with oesophagogastric cancer.	esophagus
High-throughput genotyping in metastatic esophageal squamous cell carcinoma identifies phosphoinositide-3-kinase and BRAF mutations.	BACKGROUND: Given the high incidence of metastatic esophageal squamous cell carcinoma, especially in Asia, we screened for the presence of somatic mutations using OncoMap platform with the aim of defining subsets of patients who may be potential candidate for targeted therapy. METHODS AND MATERIALS: We analyzed 87 tissue specimens obtained from 80 patients who were pathologically confirmed with esophageal squamous cell carcinoma and received 5-fluoropyrimidine/platinum-based chemotherapy. OncoMap 4.0, a mass-spectrometry based assay, was used to interrogate 471 oncogenic mutations in 41 commonly mutated genes. Tumor specimens were prepared from primary cancer sites in 70 patients and from metastatic sites in 17 patients. In order to test the concordance between primary and metastatic sites from the patient for mutations, we analyzed 7 paired (primary-metastatic) specimens. All specimens were formalin-fixed paraffin embedded tissues and tumor content was >70%. RESULTS: In total, we have detected 20 hotspot mutations out of 80 patients screened. The most frequent mutation was PIK3CA mutation (four E545K, five H1047R and one H1047L) (N = 10, 11.5%) followed by MLH1 V384D (N = 7, 8.0%), TP53 (R306, R175H and R273C) (N = 3, 3.5%), BRAF V600E (N = 1, 1.2%), CTNNB1 D32N (N = 1, 1.2%), and EGFR P733L (N = 1, 1.2%). Distributions of somatic mutations were not different according to anatomic sites of esophageal cancer (cervical/upper, mid, lower). In addition, there was no difference in frequency of mutations between primary-metastasis paired samples. CONCLUSIONS: Our study led to the detection of potentially druggable mutations in esophageal SCC which may guide novel therapies in small subsets of esophageal cancer patients.	esophagus
[Esophageal cancer surgery for patients with chronic respiratory diseases].	Esophageal cancer frequently occurs in the elderly and many of the patients have smoking history. Therefore, some of them have pulmonary comorbidity such as chronic respiratory diseases. As postoperative pulmonary complications after esophagectomy can be a cause of hospital death, careful evaluation is needed before the decision of the indication for surgery. In order to prevent postoperative pulmonary complications in patients with pulmonary comorbidities, modifications in the surgical procedures are needed. Even for cases who can tolerate standard esophagectomy, both the bronchial arteries and pulmonary branches of the vagal nerve should be preserved as far as possible. For patients who cannot tolerate the thoracotomy, transhiatal esophagectomy or non-surgical treatment should be selected. Postoperatively, airway cleansing using a bronchoscopy or mini-tracheostomy should be performed for cases with difficulty in sputum excretion. An enhanced recovery program by multidisciplinary team is effective to prevent postoperative pulmonary complications. Perioperative use of corticosteroid and sivelestat may reduce the incidence of pulmonary complications. As aspiration pneumonia is sometimes fatal in patients after esophagectomy, care to avoid aspiration is needed. Respiratory care is essential during the follow-up period as well as perioperative period in esophagectomized patients with pulmonary comorbidities.	esophagus
Clinical issues in oesophageal adenocarcinoma: could DNA copy number hold the key?	While not being considered a common cancer, since 1975 oesophageal adenocarcinoma (OAC) has had the fastest-rising incidence of any malignancy in Caucasian Western populations. In the absence of major improvements in treatment since this rise began, the number of deaths has also increased rapidly. In contrast, there have been significant advances in basic science in this period. One such advance is the discovery of DNA copy number aberrations (CNAs), and their potential role in carcinogenesis. The study of CNAs offers the potential to answer fundamental clinical questions in OAC, which in turn may lead to improved diagnosis, staging and treatment. This review outlines current clinical dilemmas in OAC, discusses the role that CNAs have been shown to play to date and highlights potential future applications.	esophagus
The involvement of serum serotonin levels producing radiation-induced bystander effects for an in vivo assay with fractionated high dose-rate (HDR) brachytherapy.	PURPOSE: The primary goal of this investigation was to observe whether measurable levels of bystander factor(s) can be detected in esophageal carcinoma patients' urine samples taken after undergoing high dose rate (HDR) intraluminal brachytherapy (ILBT). However, a small pilot study was developed to evaluate whether serotonin [5-Hydroxytryptamine (5-HT)] serum levels play an active role in the mechanisms of radiation-induced bystander effects (RIBE) at high doses. MATERIALS AND METHODS: In the present study, a colony-forming in vivo assay was developed and used for the detection of non-targeted effects. Samples of urine were collected from five esophageal carcinoma patients undergoing fractionated HDR-ILBT. To observe whether 5-HT modulates the bystander effect at higher doses, different batches of foetal bovine serum (FBS) and 5-HT were tested on the same urine samples before and after brachytherapy. RESULTS: Some of our data suggests statistically significant evidence for serotonin playing an active role as a signalling molecule at higher doses when patients underwent HDR-ILBT. CONCLUSION: However, a more thorough investigation, with a larger sample size, is warranted before serotonin can be known to play a role in bystander effects at this particular dose range and treatment regime.	esophagus
Polymorphisms in the ERCC5 gene and risk of esophageal squamous cell carcinoma (ESCC) in Eastern Chinese populations.	BACKGROUND: Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair; its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus contribute to cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: In a hospital-based case-control study of 1115 esophageal squamous cell carcinoma (ESCC) cases and 1117 cancer-free controls, we genotyped three potentially functional SNPs of ERCC5 (SNPs, rs2296147T>C, rs2094258C>T and rs873601G>A) and estimated crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for their associations with risk of ESCC using unconditional logistic regression models. We also calculated false-positive report probabilities (FPRPs) for significant findings. We found that compared with the TT genotype, ERCC5 rs2296147 C variant genotypes were associated with a significantly lower ESCC risk (CT: adjusted OR = 0.76, 95% CI = 0.63-0.93, CT/CC: adjusted OR = 0.80, 95% CI = 0.67-0.96); however, this risk was not observed for the other two SNPs (rs2094258C>T and rs873601 G>A), nor in further stratification and haplotype analysis. CONCLUSIONS/SIGNIFICANCES: These findings suggested that ERCC5 polymorphisms may contribute to risk of ESCC in Eastern Chinese populations, but the effect was weak and needs further validation by larger population-based case-control studies.	esophagus