crossing96/oncoscreening huggingface dataset:
The importance of exposure rate on odds ratios by cigarette smoking and alcohol consumption for esophageal adenocarcinoma and squamous cell carcinoma in the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium.	BACKGROUND: Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration. METHODS: The authors pooled data from 12 case-control studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1242 (EAC), 1263 (EGJA) and 954 (ESCC) cases and 7053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux. RESULTS: For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P<0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5 drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P=0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P<0.01). CONCLUSIONS: Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases.	esophagus
Time trends in educational differences in lung and upper aero digestive tract cancer mortality in France between 1990 and 2007.	BACKGROUND: We investigated the magnitude of educational differences in lung and upper aero digestive tract (UADT) cancer mortality in France from 1990 to 2007. METHODS: The analyses were based on census data from a representative sample of the French population. Educational level was used as the indicator for socioeconomic status. Educational differences in mortality from lung and UADT cancer were calculated among people aged 30-74 and by birth cohort. Two periods were compared: 1990-1998 and 1999-2007. Mortality rates, hazard ratios and relative indices of inequality (RII) were computed. RESULTS: We found higher lung and UADT cancer mortality among those with less education. Inequalities in male UADT cancer mortality remained stable over time (RII(1990-1998)=0.21 (95% confidence interval 0.15-0.29); RII(1999-2007)=0.17 (0.11-0.26)) whereas inequalities in lung cancer mortality increased among the younger men (RII(1990-1998)=0.48 (0.28-0.83); RII(1999-2007)=0.16 (0.09-0.31)). Among women, inequalities in lung cancer mortality became apparent during the second period with higher mortality among those with less education. This trend was exclusively driven by the younger women, among whom inequalities reached about the same magnitude as among younger men (RII(1999-2007)=0.21 (0.08-0.56)). CONCLUSION: UADT cancer mortality rates strongly decreased over time for every educational level. This implies that the burden of health associated with socioeconomic inequalities in UADT cancer mortality decreased substantially. Inequalities in lung cancer mortality are increasing among the younger generation and are expected to increase even more. Differences in magnitude of inequalities among men and women may disappear in the coming decades.	esophagus
Paris polyphylla Smith extract induces apoptosis and activates cancer suppressor gene connexin26 expression.	BACKGROUND: The inhibition of tumor cell growth without toxicity to normal cells is an important target in cancer therapy. One possible way to increase the efficacy of anticancer drugs and to decrease toxicity or side effects is to develop traditional natural products, especially from medicinal plants. Paris polyphylla Smith has shown anti-tumour effects by inhibition of tumor promotion and inducement of tumor cell apoptosis, but mechanisms are still not well understood. The present study was to explore the effect of Paris polyphylla Smith extract (PPSE) on connexin26 and growth control in human esophageal cancer ECA109 cells. METHODS: The effects of PPSE on Connexin26 were examined by RT-PCR, western blot and immunofluorescence; cell growth and proliferation were examined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. RESULTS: PPSE inhibited the growth and proliferation on esophageal cancer ECA109 cells, while increasing the expression of connexin26 mRNA and protein; conversely, PPSE decreased Bcl-2 and increased Bad. CONCLUSION: This study firstly shows that PPSE can increase connexin26 expression at mRNA and protein level, exerting anti-tumour effects on esophageal cacner ECA109 cells via inhibiting cell proliferation and inducing cell apoptosis.	esophagus
Advanced gastroesophageal carcinoma: an update on the current therapeutic landscape.	Gastroesophageal cancers are usually diagnosed in an advanced stage, and effective treatment options remain limited. The discovery of new drugs to treat these diseases has been slow for decades. An occasional favorable outcome, trastuzumab, in patients with HER2 protein-overexpressing tumors, is welcome but not sufficient. For advanced gastroesophageal adenocarcinoma (AGC), fluoropyrimidines (given orally or intravenously) plus a platinum compound (usually cisplatin) have been accepted as a global reference to streamline new drug development. The addition of a third cytotoxic (docetaxel or epirubicin) can produce modest prolongation of overall survival. In some European countries, the irinotecanbased regimen is considered as an alternative to platinum-based first-line therapy. Selecting a safe, effective, and convenient regimen is desirable and is the focus of current research. Additionally, it appears that survival differences by regions (e.g., Asians survive longer compared to Western and South American patients) are likely due to second- and third-line therapies, differences in tumor biology, or unknown reasons. Future progress could come from 1 of 2 approaches: (1) conducting many empiric phase III trials in unselected patients or (2) through detailed studies of molecular biology to develop rational therapies. We provide a brief update on the treatment of AGC.	esophagus
Diagnostic transgastric endoscopic peritoneoscopy for staging of pancreatic and esophageal cancer.	Pancreatic and esophageal cancers are both gastrointestinal malignancies with relatively low long term survival. In part, the aggressiveness of these tumors is related to local and distant metastatic potential, subsequently affecting prognosis and treatment modalities. Currently, the mainstay of staging involves in-depth radiographic imaging with surgery offered for potentially curative tumors. As a result, staging becomes a key determinant in the role of surgical resection. As minimally invasive approaches continue to gain popularity, the idea of natural orifice surgery has been raised as a possible adjunct to staging neoplasias. Currently, the insertion of a perioral endoscope to gain access to the peritoneal cavity via a transgastric incision has been investigated, with demonstration of feasibility and efficacy in several animal studies and limited clinical studies. Similar techniques have been employed to gain access to the thoracic cavity via a transesophageal incision in early animal studies. This article aims to outline the advantages and limitations of natural orifice endoscopic surgery, and review the use of endoscopic techniques to assess the intraperitoneal cavity via a transgastric incision for determining local and widespread metastases with reference to pancreatic carcinoma. The method of transesophageal staging for esophageal carcinoma will also be discussed.	esophagus
[Overexpression of Smac gene enhanced chemotherapeutic sensitivity of esophageal cancer cell line Eca109 to cisplatin].	AIM: To investigate the effects of Smac gene overexpression on chemotherapeutic sensitivity of esophageal cancer cell line Eca109 to cisplatin. METHODS: pcDNA3.1-Smac with GFP and pcDNA3.1-Smac with GFP were transfected into esophageal cancer cell line Eca109 by liposome and incubated with G418 for subclone selection.The efficiency of transfection was observed under fluorescence microscope, cellular Smac gene expression were determined by Western blot. Cisplatin treated group (1, 5, 10 mg/L) and cisplatin untreated group were selected to treat untransfected and transfected esophageal cancer cell line Eca109. Apoptosis was determined by Annexin V/PI. RESULTS: The subclone esophageal cancer cell line Eca109, stable expressing Smac+GFP and neo+GFP respectively, were successfully selected, named as Eca109/Smac, Eca109/neo. Compared with the Eca109/neo and Eca109, the Smac expression level of Eca109/Smac was significantly increased(P<0.05). In cisplatin untreated group, the apoptosis rate was not associated with Smac expression. In cisplatin treated group (1, 5, 10 mg/L), compared with Eca109/neo and Eca109, the apoptosis rate of the Eca109/Smac was significantly increased after the treatments of cisplatin, the difference were significant(P<0.05). In addition, the apoptosis rate of Eca109/Smac was significantly increased with the concentration of cispaltin increased(P<0.05). The difference between Eca109/neo and Eca109 were not significant. CONCLUSION: Smac gene didn't induce apoptosis in the cisplatin untreated Eca109 cells. Smac gene overexpression could increase chemotherapeutic sensitivity of esophageal cancer cell line Eca109 to cisplatin.	esophagus
Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy as definitive treatment for locally advanced, unresectable esophageal cancer: a phase-II study of the SWOG (S0414).	INTRODUCTION: The specific aims of the study were to evaluate the 2-year overall survival (OS) and progression-free survival (PFS), toxicity profile, and best objective response rate in patients with locally advanced, clinically unresectable esophageal cancer receiving cetuximab, cisplatin, irinotecan, and thoracic radiotherapy (TRT) within a multi-institutional cooperative-group setting. METHODS: Eligible patients (cT4 M0 or medically unresectable, biopsy proven, and noncervical esophageal cancer) were to receive four 21-day cycles of cetuximab 400 mg/m (day 1, cycle 1), cetuximab 250 mg/m (day 8, 15, cycle 1; then days 1, 8, and 15 for subsequent cycles), cisplatin 30 mg/m (days 1 and 8, all cycles), and irinotecan 65 mg/m (days 1 and 8, all cycles). TRT was administered at 1.8 Gy in 28 daily fractions to a total dose of 50.4 Gy, to begin with on day 1 of cycle 3. The primary endpoint was 2-year OS, with an accrual goal of 75 patients with adenocarcinoma. RESULTS: The study was closed because of slow accrual, with 21 eligible patients (11 squamous, 10 adenocarcinoma) enrolled from May 2005 to September 2007. Two-year OS and PFS (95% confidence interval [CI]) were 33.3% (14.6-57.0%) and 23.8% (8.2-47.2%), respectively. Kaplan-Meier estimates of median (95% CI) OS and PFS were 11.2 (6.4-43.6) and 6.4 (3.7-12.0) months, respectively. The overall response rate (95% CI) among 17 evaluable patients was 17.6% (3.8-43.4%), including 6% confirmed complete responders and 12% unconfirmed partial responders. Two deaths resulted from protocol treatment (sudden death and gastrointestinal necrosis). Ten (47.6%) and 6 (28.6%) patients had grade-3 or -4 toxicity, respectively: 52.4% were hematologic, 23.8% had fatigue, 19.0% had nausea, 19.0% had dehydration, and 19.0% had anorexia. CONCLUSIONS: Concomitant cetuximab, cisplatin, irinotecan, and TRT were poorly tolerated in the first North American cooperative group trial testing this regimen for locally advanced esophageal cancer as treatment-related mortality approached 10%. Single-institution phase-II cetuximab-based combined modality trials have yielded encouraging results in preliminary analyses. The SWOG GI Committee endorses enrollment to open clinical trials to clarify the therapeutic ratio of cetuximab-based combined modality approaches for esophageal cancer.	esophagus
RhoE functions as a tumor suppressor in esophageal squamous cell carcinoma and modulates the PTEN/PI3K/Akt signaling pathway.	Emerging evidence indicates that RhoE as novel member of the Rho GTPases family plays an essential role in carcinogenesis and tumor progression of human various tumors, but the functional significance of RhoE in human esophageal squamous cell carcinoma (ESCC) is still unclear. In the current study, RhoE expression in ESCC tissues and cells was examined, and the biological functions of RhoE in ESCC cells were determined. The results revealed that RhoE expression at mRNA and protein levels was significantly downregulated in ESCC tissues and cell lines (P < 0.05). RhoE expression was tightly associated with differentiation degree, clinical staging, and lymph node metastasis of the patients with ESCC (P < 0.05), but no significant correlations were found between RhoE expression and gender or age of the patients with ESCC (P > 0.05). Additionally, we found that downregulation of RhoE expression in ESCC cells promoted cell proliferation, cell cycle progression, as well as cell invasion in vitro, and inhibited cell apoptosis. Conversely, upregulation of RhoE expression in ESCC cells inhibited cell proliferation, arrested cell cycle at G0/G1 phase, reduced cell invasion, and promoted cell apoptosis. Furthermore, the downregulation of RhoE expression significantly reduced PTEN level and enhanced pAkt level; however, elevation of RhoE expression markedly increased PTEN level and decreased pAkt level. Stepwise investigations demonstrated that overexpression of RhoE in ESCC cells increased the expressions of p27 and bax proteins but decreased the expressions of cyclin D1 and bcl-2 proteins. These data demonstrate that RhoE may play a driving role in the development and progression of ESCC, and targeting the RhoE may be an effective and feasible approach for treatment of ESCC.	esophagus
Predictive value of metabolic tumor volume measured by 18F-FDG PET for regional lymph node status in patients with esophageal cancer.	OBJECTIVE: The aim of the current study was to investigate the predictive value of metabolic tumor volume (MTV) measured by (18)F-FDG PET/CT for regional lymph node (rLN) metastasis in patients with esophageal cancer. METHODS: A retrospective review identified 54 patients with surgically resected esophageal cancer who received (18)F-FDG PET/CT at diagnosis of cancer. The (18)F-FDG PET/CT findings for all primary cancer and rLN involvement were compared with the pathologic diagnosis within 5 weeks after surgical resection. The pathologic diagnoses of rLN state were confirmed by surgical resection. Univariate and multivariate analyses were used to analyze the associations among the pathologic rLN status and age, sex, T stage, location, differentiation, maximum standardized uptake value (SUV(max)), MTV2.5, and MTV3. RESULTS: The rLN(+) group showed statistically significant higher value of SUVmax than the rLN(-) group (P = 0.0011). The rLN(+) group showed statistically significant higher value of MTV2.5 (P = 0.0004) and MTV3 (P = 0.0005) than the rLN(-) group. In receiver operating characteristic analysis, the SUV(max), MTV2.5, and MTV3 did not show the statistical differences for the prediction of pathologic rLN involvement in esophageal cancer. In univariate analysis, T stage, SUV(max), MTV2.5, and MTV3 were factors significantly associated with pathologic rLN involvement. However, in multivariate analysis, the MTV2.5 and MTV3 were factors significantly associated with pathologic rLN involvement in esophageal cancer. CONCLUSION: Based on the presented results, the MTV measured by (18)F- FDG PET/CT is a useful method for the prediction of pathologic rLN status in esophageal cancer patients. Further studies are needed to confirm these results and improve statistical accuracy.	esophagus
Valproic acid, a histone deacetylase inhibitor, enhances radiosensitivity in esophageal squamous cell carcinoma.	Histone deacetylase (HDAC) inhibitors have been shown to enhance radiation response in various cancer cell lines. Valproic acid (VPA) has been used in clinical practice for the treatment of epilepsy and other seizure disorders and is also one of the most represented HDAC inhibitors. The aim of this study was to evaluate the radiosensitizing ability of VPA and its mechanisms in four esophageal squamous cell carcinoma (ESCC) cell lines (TE9, TE10, TE11 and TE14). VPA inhibited the viability of all ESCC cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) value of VPA in each cell line was between 1.02-2.15 mM, which is higher than clinically used safe concentrations. VPA induced the hyperacetylation of histones H3 and H4, as well as apoptosis and had a radiosensitizing effect on all four ESCC cell lines at a concentration of 0.5 mM which is equivalent to the therapeutic plasma concentration of anti-epilepsy therapy in humans. The radiosensitization was accompanied by an increase in γH2AX levels, indicating the presence of double-strand breaks (DSBs), and decrease in Rad51 expression, a DSB repair protein. These results suggest that a clinically safe dose of VPA can enhance radiation-induced cytotoxicity in human ESCC cells by chromatin decondensation with histone hyperacetylation and downregulation of Rad51. In conclusion, VPA appears to be a safe and promising radiosensitizer for esophageal cancer radiotherapy.	esophagus
Pre-treatment maximal oesophageal wall thickness is independently associated with response to chemoradiotherapy in patients with T3-4 oesophageal squamous cell carcinoma.	OBJECTIVES: Combined chemoradiotherapy with or without surgery is frequently performed as a curative treatment in patients with T3-4 locally advanced oesophageal squamous cell carcinoma. Computed tomography (CT) is frequently performed before and after chemoradiotherapy. The aim of this study is to evaluate the utility of the oesophageal wall thickness on CT scans to predict the response to chemoradiotherapy and the treatment outcome in patients with T3-4 locally advanced oesophageal squamous cell carcinoma. METHODS: Ninety-six patients with T3-4 locally advanced oesophageal squamous cell carcinoma, who were treated with neoadjuvant chemoradiotherapy followed by surgery between 1998 and 2008 at the Kaohsiung Chang Gung Memorial Hospital, were retrospectively reviewed. CT scans before and after chemoradiotherapy were available for 93 patients. Of these 93 patients, 24% (22 of 93) achieved a pathologically complete response (pCR). The measurement of the maximal dimension of the oesophageal wall thickness on CT scans before (pre) and after (post) chemoradiotherapy was performed retrospectively, and correlated with the response to chemoradiotherapy and patients' outcome. The percentage decrease of maximal oesophageal wall thickness after chemoradiotherapy was determined by the formula: [(pre -post)/pre] 100. RESULTS: Pre- and post-chemoradiotherapy maximal oesophageal wall thicknesses were significantly correlated with pCR, but the percent decrease of oesophageal wall thickness after chemoradiothrapy was not. Logistic models showed that pre-chemoradiotherapy maximal oesophageal wall thickness ≥20 mm was independently associated with response to chemoradiotherapy. For patients with pre-chemoradiotherapy maximal oesophageal wall thickness ≥20 mm, 91% did not achieve pCR after chemoradiotherapy. Univariate analyses demonstrated that a pre-chemoradiotherapy maximal oesophageal wall thickness ≥20 mm, T4 disease and positive regional lymph nodes (N stage) were predictive of inferior disease-free survival. In a multivariate comparison, pre-chemoradiotherapy maximal oesophageal wall thickness ≥20 mm represented an independent adverse prognosticator for disease-specific survival and disease-free survival. CONCLUSIONS: Most of the T3-4 locally advanced oesophageal squamous cell carcinoma patients with pre-treatment maximal oesophageal wall thickness ≥20 mm did not achieve pCR after chemoradiotherapy. Thus, oesophgectomy may be considered in advance in this group of patients. Pre-treatment maximal oesophageal wall thickness is of independent prognostic value in patients with T3-4 locally advanced oesophageal squamous cell carcinoma who receive neoadjuvant chemotheradiotherapy.	esophagus
The effect of socioeconomic status on staging and treatment decisions in esophageal cancer.	BACKGROUND: Optimal treatment choice for patients with esophageal cancer (EC) is complex and largely determined by tumor characteristics, comorbidity, and age. GOALS: This study describes the role of patient characteristics, among which is socioeconomic status (SES), in EC treatment. STUDY: Patients diagnosed with primary EC between 1990 and 2008 in the southern part of the Netherlands were identified using the Eindhoven Cancer Registry. Multivariable logistic and proportional hazard regression analyses were used to identify determinants of treatment and survival. RESULTS: We included 1914 patients, and 37% of them underwent intentionally curative treatment. Low-SES patients were diagnosed at older age (16% vs. 9%, age more than or equal to 80) and with more advanced tumor stages (13% vs. 10%, stage T4) than high-SES patients. Age less than 60 compared with 70 to 79 years [adjusted odds ratio, 4.51; 95% confidence interval (CI), 2.98-6.84] and high SES compared with low SES (adjusted odds ratio 1.59; 95% CI, 1.07-2.37) were independent predictors for curative treatment. Probability of death for high-SES patients undergoing palliative treatment was decreased compared with low-SES patients (hazard ratio, 0.84; 95% CI, 0.71-0.99). CONCLUSIONS: SES is an important factor in treatment choice of EC. As health care is equally accessible to the whole population in the Netherlands, this suggests that both patient-related and physician-related factors are involved in this phenomenon.	esophagus