crossing96/oncoscreening huggingface dataset:
STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer.	Hypoxia plays a key role in tumour initiation and metastasis; one of the mechanisms is to induce epithelial-mesenchymal transition (EMT). Signal transducer and activator of transcription 3 (STAT3) is involved in EMT by regulating the transcriptional regulators of E-cadherin, the biomarker of EMT. Until now, however, few studies have focused on the effects of STAT3 in hypoxia-induced EMT in tumour cells. The goal of this study was to investigate the roles of STAT3 in hypoxia-induced EMT in oesophageal squamous cell carcinoma (ESCC). The ESCC cells, TE-1 and EC-1, were incubated in normoxia, or in CoCl2, which was used to mimic hypoxia. With CoCl2, the ESCC cells showed increased migration and invasion abilities, accompanied with upregulation of HIF-1α, STAT3, and vimentin, and downregulation of E-cadherin. Knockdown of STAT3 inhibited EMT of ESCC cells and downregulated HIF-1α in vitro and in vivo. In ChIP assays, STAT3 bound to the promoter of HIF-1α, suggesting that STAT3 regulates transcription of HIF-1α. In conclusion, hypoxia induces EMT of ESCC, and STAT3 regulates this process by promoting HIF-1α expression.	esophagus
Gastric Outlet Obstruction After Esophagectomy: Retrospective Analysis of the Effectiveness and Safety of Postoperative Endoscopic Pyloric Dilatation.	BACKGROUND AND AIMS: Delayed gastric emptying after esophagectomy with gastric replacement can pose a significant postoperative problem, often leading to aspiration and pneumonia. The present study analyzes retrospectively the effectiveness of endoscopic pyloric dilatation for post-surgical gastric outlet obstruction. METHODS: Between March 2006 and March 2010, 403 patients underwent a transthoracic en-bloc esophagectomy and reconstruction with a gastric tube and intrathoracic esophagogastrostomy. In patients with postoperative symptoms of an outlet dysfunction and the confirmation by endoscopy, pyloric dilatations were performed without preference with either 20- or 30-mm balloons. RESULTS: A total of 89 balloon dilatations of the pylorus after esophagectomy were performed in 60 (15.6 %) patients. In 21 (35 %) patients, a second dilatation of the pylorus was performed. 55 (61.8 %) dilatations were performed with a 30-mm balloon and 34 (38.2 %) with a 20-mm balloon. The total redilatation rate for the 30-mm balloon was 20 % (n = 11) and 52.9 % (n = 18) for the 20-mm balloon (p < 0.001). All dilatations were performed without any complications. CONCLUSIONS: Pylorus spasm contributes to delayed gastric emptying leading to postoperative complications after esophagectomy. Endoscopic pyloric dilatation after esophagectomy is a safe procedure for treatment of gastric outlet obstruction. The use of a 30-mm balloon has the same safety profile but a 2.5 lower redilatation rate compared to the 20-mm balloon. Thus, the use of 20-mm balloons has been abandoned in our clinic.	esophagus
Enteral Access is not Required for Esophageal Cancer Patients Undergoing Neoadjuvant Therapy.	BACKGROUND: The nutritional status of esophageal cancer patients during neoadjuvant therapy remains a challenging problem. The objective of this study was to determine whether routine enteral feeding tube placement improved nutritional status and perioperative outcomes for patients undergoing neoadjuvant therapy for esophageal cancer. METHODS: The Society of Thoracic Surgeons database was used to identify patients who underwent neoadjuvant therapy and esophagectomy at our institution between 2010 and 2014. Nutritional status before and after neoadjuvant therapy was determined through standardized nutrition consultations. Predictors of change in nutrition and adverse events were evaluated with multivariable and univariate logistic regressions. RESULTS: Two hundred thirty-four esophagectomy patients were identified, and 127 (54%) received neoadjuvant therapy. Of those receiving neoadjuvant therapy, 80% (102/127) presented with dysphagia, and 48% (61/127) received enteral feeding access (EA). Multivariable regression revealed that high initial albumin level, high initial body mass index, and presence of EA were associated with nutritional stability during neoadjuvant therapy. However, 27.9% (17/61) of patients who received EA did not use their access at all or did not use it consistently during the course of preoperative treatment. The preoperative grades of malnutrition and esophagectomy outcomes were similar between groups (EA vs no EA). CONCLUSIONS: EA is associated with improved nutritional status for patients undergoing neoadjuvant therapy for esophageal cancer. However, adverse events and suboptimal use are common. Esophagectomy outcomes were similar for patients with and without EA. These results support judicious patient selection for EA, expedited neoadjuvant therapy, and close collaboration with nutritionists.	esophagus
Primary Mucosa-associated Lymphoid Tissue Lymphoma Metachronously Involving Esophagus and Stomach.	Mucosa-associated lymphoid tissue (MALT) lymphoma is found in various organs as extranodal B cell lymphoma. The gastro-intestinal tract is the most commonly involved extranodal site in MALT lymphoma. However, primary esophageal MALT lymphoma is very rare. In addition, few cases with metachronous gastric involvement have been reported. A 55-year-old man was diagnosed with MALT lymphoma by surveillance esop hagogastroduodenoscopy. A 5 cm esophageal submucosal tumor-like lesion was incidentally revealed by screening esophagogastroduodenoscopy two years prior. Esophagogastroduodenoscopy showed a cylin-drically elongated submucosal mass with normal overlying mucosa in the mid esophagus. He underwent surgery to confirm the diagnosis. The pathologic diagnosis was esophageal MALT lymp homa. He was treated with radiation, which achieved complete remission. Esophagogastroduodenoscopy and chest computed tomography were performed every three to six months, with no evidence of recurrence for 18 months. After 21 months, severa l elevated gastric erosions were found on the great curvature and posterior sides of the midbody and confirmed as MALT lymphoma pathologically. Here we report a case with MALT lymphoma metachronously involving the esophagus and stomach.	esophagus
Efficacy and Safety of Induction Chemotherapy in Esophageal Cancer with Airway Involvement.	PURPOSE: Esophageal cancer with tracheobronchial involvement (TBI) has a poor prognosis. Radical therapy carries the risk of inducing tracheoesophageal fistula (TEF) and treatment-related mortality. Induction chemotherapy followed by reassessment for radical therapy may decrease morbidity and improve outcome. METHODS: This is a retrospective analysis of esophageal cancer patients with TBI who received induction chemotherapy. Airway involvement was defined as bronchoscopic appearance of a bulge into the lumen, restricted or immobile mucosa, frank infiltration, TEF, or stridor, which was clinically due to airway obstruction from the esophageal lesion. RESULTS: Eighty-three patients were included over 5 years; 97.6 % had squamous histology. All patients received taxane and platinum combination induction chemotherapy; 90.5 % of patients received chemotherapy without dose delays, and 77.8 % patients did not require a dose reduction or modification. The 31.7 % patients had a clinically significant ≥grade 3 toxicity. The objective response rate was 67 % among the patients who underwent restaging scans following induction chemotherapy; 79.5 % of the patients could receive radical intent therapy, either concurrent chemoradiotherapy, or radiation alone, or surgery in one patient. The TEF complication rate was 6 % during the course of therapy. At a median follow-up of 28 months in surviving patients, the estimated median PFS was 8 months (95 % CI 5.5-10.5) and the estimated median OS was 17 months (95 % CI 5.6-28.4). Patients who received radical therapy had a significantly better PFS and OS, p = 0.000. CONCLUSIONS: Induction chemotherapy may improve the outcome of patients with esophageal cancer involving the airway and may help select patients for curative treatment and lower the risk of TEF development.	esophagus
Association of Physical Activity by Type and Intensity With Digestive System Cancer Risk.	IMPORTANCE: Accumulating evidence indicates that common carcinogenic pathways may underlie digestive system cancers. Physical activity may influence these pathways. Yet, to our knowledge, no previous study has evaluated the role of physical activity in overall digestive system cancer risk. OBJECTIVE: To examine the association between physical activity and digestive system cancer risk, accounting for amount, type (aerobic vs resistance), and intensity of physical activity. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study followed 43 479 men from the Health Professionals Follow-up Study from 1986 to 2012. At enrollment, the eligible participants were 40 years or older, were free of cancer, and reported physical activity. Follow-up rates exceeded 90% in each 2-year cycle. EXPOSURES: The amount of total physical activity expressed in metabolic equivalent of task (MET)-hours/week. MAIN OUTCOMES AND MEASURES: Incident cancer of the digestive system encompassing the digestive tract (mouth, throat, esophagus, stomach, small intestine, and colorectum) and digestive accessory organs (pancreas, gallbladder, and liver). RESULTS: Over 686 924 person-years, we documented 1370 incident digestive system cancers. Higher levels of physical activity were associated with lower digestive system cancer risk (hazard ratio [HR], 0.74 for ≥63.0 vs ≤8.9 MET-hours/week; 95% CI, 0.59-0.93; P value for trend = .003). The inverse association was more evident with digestive tract cancers (HR, 0.66 for ≥63.0 vs ≤8.9 MET-hours/week; 95% CI, 0.51-0.87) than with digestive accessary organ cancers. Aerobic exercise was particularly beneficial against digestive system cancers, with the optimal benefit observed at approximately 30 MET-hours/week (HR, 0.68; 95% CI, 0.56-0.83; P value for nonlinearity = .02). Moreover, as long as the same level of MET-hour score was achieved from aerobic exercise, the magnitude of risk reduction was similar regardless of intensity of aerobic exercise. CONCLUSIONS AND RELEVANCE: Physical activity, as indicated by MET-hours/week, was inversely associated with the risk of digestive system cancers, particularly digestive tract cancers, in men. The optimal benefit was observed through aerobic exercise of any intensity at the equivalent of energy expenditure of approximately 10 hours/week of walking at average pace. Future studies are warranted to confirm our findings and to translate them into clinical and public health recommendation.	esophagus
Mediastinal Adiposity Influences the Technical Difficulty of Thoracic Procedure in Minimally Invasive Esophagectomy.	BACKGROUND: Obesity is considered to influence the difficulty of surgery. However, whether mediastinal adiposity influences the difficulty of the thoracic procedure in minimally invasive esophagectomy (MIE) remains unclear. METHODS: Computed tomography volumetry was performed in 142 patients who underwent MIE between 2012 and 2014. We measured abdominal visceral fat area (AVFA) at the umbilicus level and mediastinal fat area (MFA) at the tracheal carina level. The influence of MFA on the difficulty of the thoracic procedure was assessed using the thoracic procedure duration as a parameter, and the effect of MFA on morbidity after MIE was assessed. RESULTS: MFA was significantly smaller than AVFA (p < 0.01). There was a positive correlation between them (p < 0.01). A significant positive correlation was observed between MFA and thoracic procedure duration (p < 0.01). Multivariate analysis revealed that MFA was independently correlated with prolonged thoracic procedure duration (p < 0.01). Regarding postoperative complications associated with the thoracic procedure, there were no significant differences in MFA between patients with or without pneumonia and those with or without chylothorax. Patients who experienced recurrent laryngeal nerve palsy (RLNP) had greater MFA than those who did not (p = 0.04). Multivariate analysis revealed that MFA was a significant predictor of the occurrence of RLNP (p = 0.04). CONCLUSIONS: Although the extent of mediastinal adiposity was much lesser than that of abdominal visceral adiposity, it could be a predictor of the difficulty of the thoracic procedure as well as the risk of RLNP in MIE.	esophagus
Major postoperative complications are associated with impaired long-term survival after gastro-esophageal and pancreatic cancer surgery: a complete national cohort study.	BACKGROUND: Some studies have reported an association between complications and impaired long-term survival after cancer surgery. We aimed to investigate how major complications are associated with overall survival after gastro-esophageal and pancreatic cancer surgery in a complete national cohort. METHODS: All esophageal-, gastric- and pancreatic resections performed for cancer in Norway between January 1, 2008, and December 1, 2013 were identified in the Norwegian Patient Registry together with data concerning major postoperative complications and survival. RESULTS: When emergency cases were excluded, there were 1965 esophageal-, gastric- or pancreatic resections performed for cancer in Norway between 1 January 2008, and 1 December 2013. A total of 248 patients (12.6 %) suffered major postoperative complications. Complications were associated both with increased early (90 days) mortality (OR = 4.25, 95 % CI = 2.78-6.50), and reduced overall survival when patients suffering early mortality were excluded (HR = 1.23, 95 % CI = 1.01-1.50). CONCLUSIONS: Major postoperative complications are associated with impaired long-term survival after gastro-esophageal and pancreatic cancer surgery.	esophagus
BMP4 Signaling Is Able to Induce an Epithelial-Mesenchymal Transition-Like Phenotype in Barrett's Esophagus and Esophageal Adenocarcinoma through Induction of SNAIL2.	BACKGROUND: Bone morphogenetic protein 4 (BMP4) signaling is involved in the development of Barrett's esophagus (BE), a precursor of esophageal adenocarcinoma (EAC). In various cancers, BMP4 has been found to induce epithelial-mesenchymal transition (EMT) but its function in the development of EAC is currently unclear. AIM: To investigate the expression of BMP4 and several members of the BMP4 pathway in EAC. Additionally, to determine the effect of BMP4 signaling in a human Barrett's esophagus (BAR-T) and adenocarcinoma (OE33) cell line. METHODS: Expression of BMP4, its downstream target ID2 and members of the BMP4 pathway were determined by Q-RT-PCR, immunohistochemistry and Western blot analysis using biopsy samples from EAC patients. BAR-T and OE33 cells were incubated with BMP4 or the BMP4 antagonist, Noggin, and cell viability and migration assays were performed. In addition, expression of factors associated with EMT (SNAIL2, CDH1, CDH2 and Vimentin) was evaluated by Q-RT-PCR and Western blot analysis. RESULTS: Compared to squamous epithelium (SQ), BMP4 expression was significantly upregulated in EAC and BE. In addition, the expression of ID2 was significantly upregulated in EAC and BE compared to SQ. Western blot analysis confirmed our results, showing an upregulated expression of BMP4 and ID2 in both BE and EAC. In addition, more phosphorylation of SMAD1/5/8 was observed. BMP4 incubation inhibited cell viability, but induced cell migration in both BAR-T and OE33 cells. Upon BMP4 incubation, SNAIL2 expression was significantly upregulated in BAR-T and OE33 cells while CDH1 expression was significantly downregulated. These results were confirmed by Western blot analysis. CONCLUSION: Our results indicate active BMP4 signaling in BE and EAC and suggest that this results in an invasive phenotype by inducing an EMT-like response through upregulation of SNAIL2 and subsequent downregulation of CDH1.	esophagus
[Expression and intratumoral heterogeneity of LN-5γ2 in esophageal squamous cell carcinoma].	OBJECTIVE: The present study aimed to evaluate the expression and intratumoral heterogeneity of LN-5γ2 in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of LN-5γ2 protein was examined in 135 ESCC cases by immunohistochemistry, and to analyze its relationship with the clinical relevance of patients. The protein expressions in different regions in the same tumor as well as different nests in the same region were compared. RESULTS: Moderate and high expression of LN-5γ2 protein was detected in 40.0% (54/135) of tumor tissues. Positive immunohistochemical staining was observed in 31.1% (23/74) of early stage (stages Ⅰ/Ⅱ) cases and 50.8% (31/61) of late stage (stage Ⅲ) cases, with a significant difference between these two groups (P=0.023). There was no statistical association of LN-5γ2 expression with age, sex of patients, PT sage, lymph node metastasis and degree of tumor differentiation (P>0.05). However, differential expression of LN-5γ2 protein was found at different sampling sites in the same tumor and the same sampling site in different carcinomas. CONCLUSION: High expression of LN-5γ2 is positively correlated with tumor clinical stages and there existed intratumoral heterogeneity of LN-5γ2 expression in ESCC tissues.	esophagus
Detection of Circulating Tumor Cells by Fluorescent Immunohistochemistry in Patients with Esophageal Squamous Cell Carcinoma: Potential Clinical Applications.	BACKGROUND Circulating tumor cells (CTCs) are tumor cells that leave the primary tumor site and enter the bloodstream, where they can spread to other organs; they are very important in the diagnosis, treatment, and prognosis of malignant tumors. However, few studies have investigated CTCs in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the CTCs in blood of ESCC patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS CTCs were acquired by a negative enrichment method that used magnetic activated cell sorting (MACSTM). Fluorescent immunohistochemistry (IHC) was used to identify the CTCs. Then, the positive CTC patients with ESCC were analyzed, after which the relationship between CTCs and clinicopathologic features was evaluated. RESULTS In the present study, 62 out of 140 (44.3%) patients with ESCC were positive for CTCs. The positive rate of CTCs was significantly related with stage of ESCC patients (P=0.013). However, there was no relationship between CTC status and age, sex, smoking tumor history, tumor location, differentiation of tumor, lymphatic invasion, or lymph venous invasion (P>0.05). Kaplan-Meier analysis showed that patients positive for CTCs had significantly shorter survival time than patients negative for CTCs. Multivariate analysis demonstrated that stage and CTC status were significant prognostic factors for patients with ESCC. CONCLUSIONS CTCs positivity is an independent prognostic biomarker that indicates a worse prognosis for patients with ESCC.	esophagus
Concurrent cisplatin and 5-fluorouracil versus concurrent cisplatin and docetaxel with radiotherapy for esophageal squamous cell carcinoma: a propensity score-matched analysis.	The optimal concurrent chemotherapy regimen with radiotherapy for esophageal cancer is unknown. Here, we compared the survival outcomes and toxicity of definitive chemoradiotherapy with either cisplatin/5-fluorouracil (PF) or docetaxel/cisplatin (DP) in patients with unresectable esophageal squamous cell carcinoma (ESCC). In this study, we identified 317 patients with ESCC who received PF or DP concurrently with definitive radiotherapy. PF group patients received two cycles of cisplatin (60 mg/m2) and 5-fluorouracil (300 mg/m2) at 4-week intervals during radiotherapy. DP group patients received a concurrent three-weekly schedule of docetaxel (60 mg/m2) and cisplatin (80 mg/m2) or cisplatin (25 mg/m2) and docetaxel (25 mg/m2) weekly. The overall survival (OS) and progression-free survival (PFS) were compared using propensity score (-adjusted, -weighted, -stratified, and -matched) analyses. A sensitivity analysis was performed to examine the impact of unmeasured confounders. Inverse probability of treatment weighting for propensity score demonstrated an improvement in OS and PFS with DP group in comparison with PF group (hazard ratio, 0.700; 95% CI, 0.577-0.851) and similar results were achieved with propensity score matching and stratification. Grade 3-4 esophagitis was more common (16/102 vs. 4/102) and grade 3-4 thrombopenia and skin toxicity were less common (3/102 vs. 10/102; 7/102 vs. 19/102; respectively) in the PF group than the DP group. In conclusion, concurrent chemoradiotherapy with the DP regimen resulted in better OS and PFS compared to concurrent PF regimen with tolerable toxicities in ESCC patients. Prospective randomized trials are required to confirm the efficacy of the DP regimen.	esophagus
Methylation of DAPK and THBS1 genes in esophageal gastric-type columnar metaplasia.	AIM: To explore methylation of DAPK, THBS1, CDH-1, and p14 genes, and Helicobacter pylori (H. pylori) status in individuals harboring esophageal columnar metaplasia. METHODS: Distal esophageal mucosal samples obtained by endoscopy and histologically diagnosed as gastric-type (non-specialized) columnar metaplasia, were studied thoroughly. DNA was extracted from paraffin blocks, and methylation status of death-associated protein kinase (DAPK), thrombospondin-1 (THBS1), cadherin-1 (CDH1), and p14 genes, was examined using a methyl-sensitive polymerase chain reaction (MS-PCR) and sodium bisulfite modification protocol. H. pylori cagA status was determined by PCR. RESULTS: In total, 68 subjects (33 females and 35 males), with a mean age of 52 years, were included. H. pylori cagA positive was present in the esophageal gastric-type metaplastic mucosa of 18 individuals. DAPK, THSB1, CDH1, and p14 gene promoters were methylated by MS-PCR in 40 (58.8%), 33 (48.5%), 46 (67.6%), and 23 (33.8%) cases of the 68 esophageal samples. H. pylori status was associated with methylation of DAPK (P = 0.003) and THBS1 (P = 0.019). CONCLUSION: DNA methylation occurs in cases of gastric-type (non-specialized) columnar metaplasia of the esophagus, and this modification is associated with H. pylori cagA positive infection.	esophagus
Predictive role of host constitutive variants in neoadjuvant therapy of esophageal cancer.	Chemoradiotherapy followed by surgery is at present the standard therapeutic approach for esophageal cancer (EC) in patients with resectable tumor. However, response to neoadjuvant therapy is characterized by a strong interpatient variability, and the identification of markers predictive of outcome is mandatory. In this review, taking into account the currently available literature, we report the impact that host genetic variables can have on EC neoadjuvant therapy. We mainly focused on the gene variants involved in the pharmacokinetics and pharmacodynamics of the common chemotherapeutic drugs used to treat EC patients, commented on the weakness of the present knowledge, and discussed the future strategies to achieve a more personalized and effective EC treatment.	esophagus