crossing96/oncoscreening huggingface dataset:
Phase 2 trial of induction and concurrent chemoradiotherapy with weekly irinotecan and cisplatin followed by surgery for esophageal cancer.	BACKGROUND: Preoperative chemoradiation improves survival in esophageal and gastroesophageal junction (GEJ) cancer. We evaluated irinotecan and cisplatin as induction chemotherapy followed by concurrent chemoradiation in esophageal cancer. METHODS: Patients with uT1N1M0 or uT2-4NanyM0 resectable squamous cancer or adenocarcinoma of the esophagus or GEJ received irinotecan 65 mg/m(2) and cisplatin 30 mg/m(2) for 4 treatments in weeks 1 through 5, followed by 4 treatments in weeks 7 through 11 with 50.4 Gy in daily fractions, followed by surgery. The primary endpoint was pathologic complete response (pCR). Positron emission tomography (PET) scan was performed prior to chemotherapy and as restaging prior to radiotherapy. RESULTS: Fifty-five patients were evaluable, 75% of whom had adenocarcinoma and 65% of whom had uT3N1 disease. Thirty-eight patients underwent R0 resection (69%). The incidence of pCR was 16% (95% confidence interval, 8%-29%). Median overall survival was 31.7 months. An exploratory analysis of PET response to induction chemotherapy indicated a correlation with pCR (32% vs 4%), R0 resection (84% vs 57%), progression-free survival (24.1 vs 7.7 months), and overall survival (40.2 vs 25.5 months). CONCLUSIONS: Weekly treatment with irinotecan, cisplatin, and radiation achieved results no better and potentially inferior to other phase 2 chemoradiotherapy trials with a low rate of pCR. The use of PET scan after induction chemotherapy to direct chemotherapy during subsequent radiotherapy merits further study.	esophagus
Cox2 and β-catenin/T-cell factor signaling intestinalize human esophageal keratinocytes when cultured under organotypic conditions.	The incidence of esophageal adenocarcinoma (EAC) is rising in the United States. An important risk factor for EAC is the presence of Barrett esophagus (BE). BE is the replacement of normal squamous esophageal epithelium with a specialized columnar epithelium in response to chronic acid and bile reflux. However, the emergence of BE from squamous keratinocytes has not yet been demonstrated. Our research has focused on this. Wnt and cyclooxygenase 2 (Cox2) are two pathways whose activation has been associated with BE and progression to EAC, but their role has not been tested experimentally. To explore their contribution, we engineered a human esophageal keratinocyte cell line to express either a dominant-active Wnt effector CatCLef or a Cox2 complementary DNA. In a two-dimensional culture environment, Cox2 expression increases cell proliferation and migration, but neither transgene induces known BE markers. In contrast, when these cells were placed into three-dimensional organotypic culture conditions, we observed more profound effects. CatCLef-expressing cells were more proliferative, developed a thicker epithelium, and upregulated Notch signaling and several BE markers including NHE2. Cox2 expression also increased cell proliferation and induced a thicker epithelium. More importantly, we observed cysts form within the epithelium, filled with intestinal mucins including Muc5B and Muc17. This suggests that Cox2 expression in a three-dimensional culture environment induces a lineage of mucin-secreting cells and supports an important causal role for Cox2 in BE pathogenesis. We conclude that in vitro modeling of BE pathogenesis can be improved by enhancing Wnt signaling and Cox2 activity and using three-dimensional organotypic culture conditions.	esophagus
Does the timing of esophagectomy after chemoradiation affect outcome?	BACKGROUND: After neoadjuvant chemoradiation (CXRT) for esophageal cancer, surgery has traditionally been recommended to be performed within 8 weeks. However, surgery is often delayed for various reasons. Data from other cancers suggest that delaying surgery may increase the pathologic complete response rate. However, there are theoretical concerns that waiting longer after radiation may lead to a more difficult operation and more complications. The optimal timing of esophagectomy after CXRT is unknown. METHODS: From a prospective database, we analyzed 266 patients with resected esophageal cancer who were treated with neoadjuvant CXRT from 2002 to 2008. Salvage resections were excluded from this analysis. We compared patients who had surgery within 8 weeks of CXRT and those who had surgery after 8 weeks. We used multivariable analysis to determine whether increased interval between chemoradiation and surgery was independently associated with perioperative complication, pathologic response, or overall survival. RESULTS: One hundred fifty patients were resected within 8 weeks and 116 were resected greater than 8 weeks after completing CXRT. Mean length of operation, intraoperative blood loss, anastomotic leak rate, and perioperative complication rate were similar for the two groups. Pathologic complete response rate and overall survival were also similar for the two groups (p=not significant). In multivariable analysis, timing of surgery was not an independent predictor of perioperative complication, pathologic complete response, or overall survival. CONCLUSIONS: The timing of esophagectomy after neoadjuvant CXRT is not associated with perioperative complication, pathologic response, or overall survival. It may be reasonable to delay esophagectomy beyond 8 weeks for patients who have not yet recovered from chemoradiation.	esophagus
Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study.	Prospective epidemiologic data on vegetables and fruits consumption and risk of subtypes of esophageal and gastric cancer are sparse. We studied the association between vegetables and fruits consumption and risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in the Netherlands Cohort Study. In 1986, 120,852 Dutch men and women aged 55-69 filled out a questionnaire on diet and other cancer risk factors. After 16.3 years of follow-up, 101 ESCC, 144 EAC, 156 GCA, 460 GNCA cases and 4,035 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Multivariable adjusted incidence rate ratios (RRs) were generally below unity. Total vegetable consumption was nonsignificantly inversely associated with EAC and ESCC risk, but not with GCA and GNCA risk. Significant inverse associations were observed for raw vegetables and EAC risk [RR per 25 g/day: 0.81, 95% confidence interval (CI) 0.68-0.98], and Brassica vegetables and GCA risk (RR per 25 g/day: 0.72, 95% CI 0.54-0.95). Total fruit consumption was associated with a nonsignificantly decreased EAC risk. Citrus fruits were inversely associated with EAC and GCA risk (RRs for highest vs. lowest intake: 0.55, 95% CI 0.31-0.98 and 0.38, 95% CI 0.21-0.69, respectively). Specifically for current smokers, vegetables and possibly also fruits intake was inversely associated with ESCC and EAC risk. Consumption of (specific groups of) vegetables and fruits may protect against subtypes of esophageal and gastric cancer.	esophagus
Increase in serum platelet-derived growth factor (PDGF)-BB reflects lymph node involvement in esophageal cancer patients independently from platelet count.	AIM: To evaluate clinical significance and diagnostic utility of increase in serum PDGF-BB (sPDGF-BB) in esophageal cancer, which have not been addressed yet despite the relevance of PDGF axis in this cancer type. METHODS: Immunoenzymatically assessed sPDGFBB was related to clinicopathological features, and inflammatory, angiogenic, and lymphangiogenic indices in 84 patients with esophageal cancer and 47 controls. Its diagnostic utility was evaluated by receiver operating characteristics (ROC) curve analysis. RESULTS: sPDGF-BB was significantly higher in esophageal cancer patients than controls (3.76 vs. 2.66 μg/l, p = 0.0001) and corresponded with the disease advancement. Of evaluated clinicopathological features, lymph node metastases and distant metastases were independently associated with an increase in sPDGF-BB; however, only the association with lymph node metastases persist adjustment to platelets. In univariate analysis, sPDGF positively correlated with platelets (r=0.70, p < 0.0001), vascular endothelial growth factor (VEGF)-A (r=0.50, p < 0.0001), VEGF-C (r=0.57, p < 0.0001), white blood cells (r=0.32, p = 0.004), C-reactive protein (r=0.34, p = 0.004), IL-6 (r=0.35, p = 0.003), and IL-8 (r=0.45, p < 0.0001). In multivariate analysis, VEGF-C and platelets were independently associated with sPDGF-BB explaining 61% in its variability. With >2.845 μg/l cut-off, over 76% of patients had elevated sPDGF-BB. Its accuracy as lymph node metastases marker was 75%, sensitivity and specificity corresponding with >3.029 μg/l cut-off were 84 and 61%, respectively. CONCLUSIONS: sPDGF-BB owns potential as a possible lymph node metastases marker and might be considered as a diagnostic tool in preliminary evaluation of esophageal cancer patients identifying those likely to be burdened with lymph node metastases, the disease recurrence monitoring, and/or preselecting patients for PDGF-directed cancer therapies.	esophagus
Gastric tube reconstruction reduces postoperative gastroesophageal reflux in adenocarcinoma of esophagogastric junction.	BACKGROUND: The anastomosis of gastric remnant to esophagus after proximal gastrectomy is the traditional surgical treatment procedure for patients with types II and III adenocarcinoma of esophagogastric junction. However, the postoperative complications such as gastroesophageal reflux are frequent. AIMS: To assess the outcome of the intraperitoneal anastomosis of the reconstructed gastric tube to esophagus after proximal gastrectomy for types II and III adenocarcinoma of esophagogastric junction. METHODS: Seventy-six consecutive patients with preoperative diagnosis of type II or type III adenocarcinoma of esophagogastric junction were recruited. Forty-one patients had the traditional anastomosis of gastric remnant to esophagus and 35 patients underwent an anastomosis of esophagus to a gastric tube that was constructed from the gastric remnant after proximal gastrectomy. RESULTS: Twenty-three (56.1%) versus 12 (28.6%) patients (p = 0.016) complained various discomforts and/or were diagnosed with complications in the traditional group and gastric tube group, respectively, although there were no significant differences between the two groups in demographic data and pathological characteristics. Fourteen (34.1%) versus five (14.3%) patients (p = 0.046) complained of heartburn or acid regurgitation and nine (22.0%) versus two (5.7%) patients (p = 0.045) were confirmed reflux esophagitis in the traditional group and the gastric tube group, respectively. CONCLUSIONS: The intraperitoneal anastomosis of the reconstructed gastric tube to esophagus demonstrates less complaints of gastroesophageal reflux and reflux esophagitis than the traditional anastomosis of gastric remnant to esophagus in the surgical treatment of types II and III adenocarcinoma of esophagogastric junction in 1-year follow-up.	esophagus
Association of methylenetetrahydrofolate reductase C677T-A1298C polymorphisms with risk for esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.	Incidence of the esophagus adenocarcinoma has been dramatically increasing in Western countries since the last decade. Gastroesophageal reflux disease and Barrett's esophagus are risk factors for adenocarcinoma. Methylenetetrahydrofolate reductase (MTHFR) genes play a key role not only in folate metabolism but also in esophagus, stomach, pancreatic carcinoma, and acute leukemias. Studies have suggested that genetic polymorphisms of MTHFR (C677T) may clarify the causes and events involved in esophageal carcinogenesis. In this study, we evaluated MTHFR C677T and A1298C polymorphisms, and vitamin B12, folate, and plasma homocystein levels in patients with esophageal adenocarcinoma (EAC), Barrett's esophagus (BE), chronic esophagitis, and healthy controls (n = 26, n = 14, n = 30, and n = 30, respectively). The mean age of patients in the EAC and BE groups was significantly higher compared with the control group (P < 0.001, P = 0.003, respectively). In all patient groups, serum folate levels were significantly lower than that of the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). There was no statistically significant association between folate levels and MTHFR gene polymorphisms. No differences were found in terms of MTHFR gene polymorphisms, homocystein, and B12 levels among the groups. MTHFR gene polymorphisms and folate deficiency are not predictors of early esophageal carcinoma. However, further studies using larger series of patients are needed to evaluate the effect of genetic polymorphisms in the folate metabolic pathway and to clarify the role of folate deficiency and folate metabolism in the development of esophagus adenocarcinoma.	esophagus
Long-term outcomes following neoadjuvant chemoradiotherapy in patients with clinical T2N0 esophageal squamous cell carcinoma.	The optimal treatment for patients with local esophageal cancer (cT2N0 disease) has not yet been defined. We sought to determine whether neoadjuvant chemoradiotherapy (CRT) can improve prognosis compared with direct esophagectomy in this patient group. Between 1994 and 2005, patients with cT2N0 esophageal squamous cell carcinoma who underwent either neoadjuvant CRT or surgery as first-line treatment were retrospectively reviewed. We collected information on their demographic characteristics, staging modality, clinical and pathological stages, perioperative course, and survival. The study endpoints included tumor recurrence, disease-specific survival (DSS), and overall survival rate. Of the 71 eligible patients, 14 received an esophagectomy first, whereas the remaining 57 received neoadjuvant CRT first. Despite the high pathological complete response (pCR) rate of 37% after neoadjuvant CRT, routine neoadjuvant CRT did not translate into better survival compared to direct surgery (5-year DSS: 39% vs. 68%, P= 0.17). The dramatic survival difference between pCR and non-pCR patients (5-year DSS: 85% vs. 4%, P < 0.001) accounts for these unsatisfactory results. In our series, the administration of neoadjuvant CRT to patients with clinical stage T2N0 esophageal squamous cell carcinoma did not significantly improve outcomes compared with direct esophagectomy.	esophagus
Esophageal disease in pediatrics.	The following on esophageal disease in pediatrics contains commentaries on acquisition of neuromuscular maturation; physiology of esophageal peristaltic and sphincteric reflexes; implications for clinical practice; and conditions that predispose to severe gastroesophageal reflux disease (GERD) in children with potential risk for esophageal cancer.	esophagus
Barrett's esophagus: treatments of adenocarcinomas II.	The following topics are explored in this collection of commentaries on treatments of adenocarcinomas related to Barrett's esophagus: the importance of intraoperative frozen sections of the margins for the detection of high dysplasia; the preferable way for sentinel node dissection; the current role of robotic surgery and of video-endoscopic approach; the value of the Siewert's classification of adenocarcinomas; the indications of two-step esophagectomy; the evaluation of pathological complete response; the role of PET scan in staging and response assessment; the role of p53 in the selection of adenocarcinomas patients; chemotherapy regimens for adenocarcinomas; the use of monoclonal antibodies in the control of cell proliferation; he attempt to define a stage-specific strategy, and the possible indications of selective therapy; and changes in mortality rates from esophageal cancer.	esophagus
[Multidisciplinary therapy for multi-focal esophageal cancer].	OBJECTIVE: To explore the management strategies and outcome of treatment for multi-focal esophageal carcinoma. METHODS: Twenty two patients with multi-focal esophageal carcinoma who underwent esophagectomy by a single surgeon team from March 2000 to March 2011 at the Beijing Cancer Hospital were reviewed retrospectively. The clinical and pathological characters were analyzed, and the outcome was compared with that of 471 patients with single esophageal carcinoma who received esophagectomy by the same surgeon team during the same period. RESULTS: Eighteen out of 22 patients with multi-focal esophageal cancer underwent esophagectomy via transthoracic approach while 4 patients via transhiatal. Eight patients received neoadjuvant chemotherapy and 15 patients received adjuvant chemotherapy. Four hundred and seventy-one out of 471 patients with single esophageal cancer underwent esophagectomy via transthoracic approach while 60 patients via transhiatal. One hundred and fourty-eight patients received neoadjuvant chemotherapy and 267 patients received adjuvant chemotherapy. The 3-year survival of the 22 patients with multi-focal esophageal carcinoma was 41.9%, and the median survival time was 29.2 months. The 3-year survival of the 471 patients with single esophageal carcinoma was 54.7%, and the median survival time was 46.8 months. There was no significant difference in survival between the two groups(P=0.051). CONCLUSIONS: The prognosis of patients with multi-focal occurrence esophageal carcinoma was poor. Extended esophageal resection may be beneficial to these patients with concurrent systemic chemotherapy.	esophagus
Vitamin d receptor gene variants and esophageal adenocarcinoma risk: a population-based case-control study.	PURPOSE: Polymorphisms in the vitamin D receptor (VDR) gene may be of etiological importance in determining cancer risk. The aim of this study was to assess the association between common VDR gene polymorphisms and esophageal adenocarcinoma (EAC) risk in an all-Ireland population-based case-control study. METHODS: EAC cases and frequency-matched controls by age and gender recruited between March 2002 and December 2004 throughout Ireland were included. Participants were interviewed, and a blood sample collected for DNA extraction. Twenty-seven single nucleotide polymorphisms in the VDR gene were genotyped using Sequenom or TaqMan assays while the poly(A) microsatellite was genotyped by fluorescent fragment analysis. Unconditional logistic regression was applied to assess the association between VDR polymorphisms and EAC risk. RESULTS: A total of 224 cases of EAC and 256 controls were involved in analyses. After adjustment for potential confounders, TT homozygotes at rs2238139 and rs2107301 had significantly reduced risks of EAC compared with CC homozygotes. In contrast, SS alleles of the poly(A) microsatellite had significantly elevated risks of EAC compared with SL/LL alleles. However, following permutation analyses to adjust for multiple comparisons, no significant associations were observed between any VDR gene polymorphism and EAC risk. CONCLUSIONS: VDR gene polymorphisms were not significantly associated with EAC development in this Irish population. Confirmation is required from larger studies.	esophagus
Prognosis of esophageal squamous cell carcinoma in patients positive for human epidermal growth factor receptor family can be improved by initial chemotherapy with docetaxel, fluorouracil, and cisplatin.	BACKGROUND: The human epidermal growth factor receptor (HER) family, Ki-67 and p53 are important biomarkers for several malignancies. However, few studies have examined the role of these in prognosis and therapeutic sensitivity of esophageal squamous cell carcinoma (ESCC). The efficacy of triple-drug combination therapy with docetaxel, fluorouracil and cisplatin has recently been expected for ESCC. METHODS: Subjects comprised 142 patients with ESCC who underwent operation (OP group, n = 54), neoadjuvant chemotherapy with docetaxel, fluorouracil, and cisplatin (DFP therapy) followed by operation (NAC group, n = 37) or initial systemic DFP therapy (CT group, n = 51) between January 2004 and December 2010. Immunohistochemical expressions of epidermal growth factor receptor (EGFR), HER2, HER3, Ki-67, and p53 were evaluated and compared with prognosis and sensitivity to DFP therapy. RESULTS: Positive correlations existed between EGFR, HER2, and HER3 expressions. In the OP group, EGFR was independently associated with postoperative recurrence in multivariate analysis (P = .036). In the NAC group, EGFR correlated with pathological response to DFP therapy (P = .004). In the CT group, EGFR, HER2, and HER3 correlated with clinical response to DFP therapy and EGFR was independently associated with favorable prognosis in multivariate analysis (P = .022). CONCLUSION: EGFR represents a predictor of postoperative recurrence and sensitivity to triple-drug combination therapy including a taxane. EGFR-positive patients may show improved prognosis with taxane combination chemotherapy and molecular targeted therapy for HER family members.	esophagus
Identification of a DNA methylome signature of esophageal squamous cell carcinoma and potential epigenetic biomarkers.	Esophageal squamous cell carcinoma (ESCC) is believed to arise from esophageal mucosa through accumulation of both genetic and epigenetic changes. DNA methylation is a critical epigenetic mechanism involved in key cellular processes and its deregulation has been linked to many human cancers, including ESCC. The aim of this study is to examine the global deregulation of methylation states in ESCC and identify potential early biomarkers. With this purpose, we performed a bead array analysis of more than 800 cancer-related genes in ten ESCC samples, ten matched surrounding tissues and four esophageal mucosa from healthy individuals. Pyrosequencing was used for validation of DNA methylation changes in up to 106 cases and 27 controls. A total of 37 CpG sites were found to be differentially methylated between tumors and surrounding tissues. These CpG sites were significantly enriched in genes related to several pathways including IL-10 anti-inflammatory signaling pathway and cell communication pathway. In addition, by comparing with healthy esophageal mucosa, we identified TFF1 gene as a potential early marker of ESCC. This is the first study to address methylation changes in ESCC in a large set of genes. Methylome analysis is shown as a sensitive and powerful tool to identify molecular players in ESCC. These data should prove to be the reference for future studies identifying potential biomarkers and molecular targets in ESCC.	esophagus