crossing96/oncoscreening huggingface dataset:
Rechallenge with platinum plus fluoropyrimidine +/- epirubicin in patients with oesophagogastric cancer.	PURPOSE: There is no standard second-line therapy for patients with oesophagogastric cancer who progress following first-line chemotherapy for advanced disease or relapse following radical multi-modality therapy. The aim of this retrospective study was to evaluate survival following rechallenge with platinum plus fluoropyrimidine (PF) +/- epirubicin. METHODS: Patients treated with PF +/- epirubicin for oesophagogastric cancer at our institution were identified from the electronic prescribing database. Patients rechallenged with PF +/- epirubicin >3 months after completing initial chemotherapy were eligible. Primary endpoint was survival, calculated from day 1 of rechallenge treatment to date of death or last follow-up. Secondary endpoints were progression-free survival and response rate to PF-based re-challenge. RESULTS: Between 2000 and 2008, 950 patients treated with PF +/- epirubicin for oesophagogastric cancer were identified. 298 patients progressed or relapsed >3 months after completing chemotherapy, of whom 106 patients were rechallenged with PF-based chemotherapy. Median progression-free survival and overall survival were 5.1 and 10 months, respectively, from date of rechallenge for patients treated with initial radical intent and 3.9 and 6.6 months, respectively, in patients treated with palliative intent from diagnosis. In a survival analysis, no significant prognostic factors were identified. CONCLUSION: Selected patients with oesophagogastric cancer who relapse or progress >3 months after initial treatment with PF +/- epirubicin may benefit from re-introduction of PF-based chemotherapy.	esophagus
CIP2A is overexpressed in esophageal squamous cell carcinoma.	A human oncoprotein-designed cancerous inhibitor of PP2A (CIP2A) has been recently identified, which can stabilize c-Myc protein by inhibiting its degradation mediated by protein phosphatase 2A (PP2A) in tumor cells and promote the proliferation of various cancer cells. Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with poor prognosis worldwide. However, the underlying molecular mechanism of the development of ESCC is still poorly understood. In the present study, the CIP2A expression between normal and malignant esophageal tissues was compared by immunohistochemical analysis; moreover, the mechanisms of CIP2A-mediated tumorigenesis were investigated by evaluating its role in cell proliferation, cell cycle, apoptosis and senescence. We found that the positive staining of CIP2A was found in 36 of 40 (90%) of cancer tissues, whereas only 8 of 40 (20%) normal esophageal mucosa exhibited positive CIP2A staining. The CIP2A is significantly overexpressed in human esophageal tumors when compared with normal tissues (χ(2) = 39.6, P < 0.01). On the other hand, the CIP2A expression was not associated with age, gender, tumor burden, or differentiation status. Depletion of CIP2A expression led to impaired clonogenicity and senescence, which is the primary mechanism of CIP2A in oncogenesis. Therefore, CIP2A may be a candidate in diagnosis and therapy of esophageal cancer.	esophagus
Endoscopic ablation therapy of Barrett's esophagus.	"Barrett's esophagus (BE) is an important risk factor for esophageal carcinoma and its incidence is rising. Amongst the various available endoscopic ablative therapies, radiofrequency ablation (RFA) is currently regarded as the most promising one, since RFA achieves high eradication rates of dysplasia and intestinal metaplasia with minimal complications. Patients with BE are advised to undergo regular endoscopic surveillance for dysplasia or cancer and endoscopy with four quadrant biopsy sampling at intervals of 1-2 cm of the entire length of BE remains the current standard for the detection of dysplasia or cancer. The management of BE depends on the histology of the biopsy specimens obtained during endoscopy, which includes non-dysplastic BE (ND-BE), low grade dysplasia, high grade dysplasia and adenocarcinoma. However, histological evaluation of dysplasia is fraught with error because of inter-observer variability even among expert gastrointestinal pathologists, and as a result, it often leads to false-negative or false-positive diagnoses. Non-dysplastic mucosa in BE shows clonal molecular aberrations, loss of cell cycle control, and other features of ""neoplasia"". These changes occur prior to morphologic expression of neoplasia (dysplasia). Given the difficulties of dysplasia assessment in mucosal biopsies, the molecular characteristics of ND-BE and LGD, and safe and effective profiles of RFA, this technique should be considered as a treatment option for the whole spectrum of BE patients."	esophagus
8-oxo-7,8-dihydro-2'-deoxyguanosine as a biomarker of oxidative damage in oesophageal cancer patients: lack of association with antioxidant vitamins and polymorphism of hOGG1 and GST.	BACKGROUND: The present report was designed to investigate the origins of elevated oxidative stress measured in cancer patients in our previous work related to a case-control study (17 cases, 43 controls) on oesophageal cancers. The aim was to characterize the relationship between the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), antioxidant vitamins and genetic susceptibility. METHODS: 8-oxodG was analysed in peripheral blood mononuclear cells (PBMCs) by High Performance Liquid Chromatography with Electrochemical Detection (HPLC-ED). Analysis of gene polymorphisms in GSTM1 and GSTT1 was performed by multiplex PCR and in GSTP1 and hOGG1 by a PCR-RFLP method. Reversed-phase HPLC with UV detection at 294 nm was used to measure vitamins A and E in serum from the same blood samples. RESULTS: We observed that in our combined population (cases and control, n = 60), there was no statistically significant correlation between the levels of 8-oxodG and (i) the serum concentration of antioxidant vitamins, vitamin A (P = 0.290) or vitamin E (P = 0.813), or (ii) the incidence of the Ser326Cys polymorphic variant (P = 0.637) of the hOGG1 gene. Also, the levels of 8-oxodG were not significantly associated with polymorphisms in metabolite-detoxifying genes, such as GSTs, except for the positive correlation with Val/Val GST P1 allele (P < 0.0001). CONCLUSIONS: The weakness of our cohort size notwithstanding, vitamins levels in serum and genetic polymorphisms in the hOGG1 or GST genes do not appear to be important modulators of 8-oxodG levels.	esophagus
Catalase, carbonic anhydrase and other biochemical parameters in esophageal cancers in Turkey.	PURPOSE: The main aim of our investigation is to show possible changes in antioxidant balance and selected biochemical parameters in esophageal cancers. MATERIALS AND METHODS: This study was performed for the determination of levels in 25 patients diagnosed as having cancer in the Yuzuncu Yil University (Medical Oncology) and 15 healthy volunteers at same department with negative cancer signs. RESULTS: The activity levels of catalase of sick and health groups were 33.8±4.31 (EU/gHg)-1, 122.4±31.7 (EU/gHg)-1, respectively. Th differance between the average levels was significant (p<0.001). CA (carbonic anhydrase) activity was 2.19±0.12 (EU/gHg)-1, 2.46±0.32 (EU/gHg)-1 in groups at same order with no statistical significance (p>0.05). The levels of albumin, globulin, ferritin, ALT, LDH, glucose, CRP, AST and uric acid were also determined in sick and healthy groups: 4.04±0.24, 4.04±0.43 gr/dl (p>0.05); 4.46±0.82, 3.17±0.10g/dl (p>0.05); 175.4±29.1, 260.4±15.45g/dI (p<0.001); 12.7±1.13, 19.5±1.91 ng/ml (p<0.001); 317.6±13.8, 298.0±12.1 mg/dl (p>0.05); 106.5±12.1, 89.7±2.2 (p>0.05), 5.94±1.04, 4.41±0.28 U/L (p>0.05); 19.4±1.68, 19.5±1.91 mg/dl (p>0.05); 30.0±3.24, 10.5±0.64 mg/dl (p<0.01) respectively. CONCLUSIONS: Consequently, in diagnosis of esophageal cancer, CA, CRP, uric acid and antioxidant examinations may be very important factors. Additional studies are needed to further address this important issue.	esophagus
Epidemiology of esophageal lesions in patients with head and neck squamous cell carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is disturbing because of its aggressive clinical path and high mortality rate. The aim of this study was to investigate the characteristics of premalignant lesions and cancer of the esophagus in patients with a history of head and neck SCC. METHODS: One hundred consecutive patients were investigated for diagnosis of superficial esophageal SCC. Lesions and their invasive depth for determination of the optimal method of treatment, and endoscopic examinations were carried out using Lugol chromoendoscopy. During endoscopy all abnormalities were investigated using approximately 10 ml of a 2% Lugol iodine solution sprayed over the entire esophageal mucosa using a spray catheter. RESULTS: The mean±SD of age was 59.1±11.0 years. The tumor location in most patients (in both men and women)was the glottis. The statistical analysis showed significant differences between male and female in glottis and tongue. Twenty percent of patients reported the history of alcohol consumption and 22 percent were smokers, with 20.3% of men and 28.6% of women having digestive symptoms. The most common symptom in men was dysphagy and in women was odynophagy. CONCLUSION: In common, men are at high risk for ESCC and a high percent of current tobacco smokers, passive smokers and the history of alcohol intake were observed. In conclusion people in these high-risk groups would greatly benefit by acquisition of knowledge about and participating in a screening program.	esophagus
Genetic aberrations in primary esophageal melanomas: molecular analysis of c-KIT, PDGFR, KRAS, NRAS and BRAF in a series of 10 cases.	We present a series of 10 primary esophageal melanomas of Caucasian patients characterized clinicopathologically and on the molecular level. Mutation analysis for c-Kit (exons 9, 11, 13 and 17), PDGFR (exons 12, 14 and 18), NRAS and KRAS were determined using PCR and direct sequencing. Analysis of the V600E mutation of BRAF was performed using mutation-specific PCR. Expression of c-Kit and PDGFR-A was additionally determined using immunohistochemistry. One tumor harbored a missense mutation in the c-Kit (p.F504L) and in the KRAS gene (p.G12S). A different c-Kit mutation (c.1507_1508 ins TTGCCT) was detected in another case. A third case had a V600E BRAF mutation. Using immunohistochemistry, c-Kit expression could be detected in all cases. The two cases with c-Kit mutations showed high c-Kit expression. None of the tumors showed a PDGFR mutation or expression or a NRAS mutation. We conclude that molecular analysis can identify targets for a specific therapy such as tyrosin kinase inhibitors as additional treatment option in these highly malignant tumors.	esophagus
Alterations in DNA repair efficiency are involved in the radioresistance of esophageal adenocarcinoma.	To study radioresistance in esophageal adenocarcinoma, we generated an isogenic cell line model by exposing OE33 esophageal adenocarcinoma cells to clinically relevant fractionated doses of radiation (cumulative dose 50 Gy). A clonogenic assay confirmed enhanced survival of the radioresistant OE33 subline (OE33 R). To our knowledge, we are the first to generate an isogenic model of radioresistance in esophageal adenocarcinoma. This model system was characterized in terms of growth, cell cycle distribution and checkpoint operation, apoptosis, reactive oxygen species generation and scavenging, and DNA damage. While similar properties were found for both the parental OE33 (OE33 P) cells and radioresistant OE33 R cells, OE33 R cells demonstrated greater repair of radiation-induced DNA damage. Our results suggest that the radioresistance of OE33 R cells is due at least in part to increased DNA repair.	esophagus
18-Fluorodeoxyglucose positron emission tomography as a tool for response prediction in solid tumours.	Current response guidelines for the treatment of solid tumours are based on CT criteria. Over the last decades new techniques have emerged to evaluate cancer therapy. FDG-PET scanning is a more functional imaging technique, which can measure differences in metabolic activity. Although it has a low specificity, studies show that it can outperform classical CT scanning criteria. Especially in lung, breast and oesophageal cancer it can predict response earlier in the neo-adjuvant setting. This could reduce the use of ineffective cancer therapies, reducing costs and patient toxicity, and direct patients sooner towards effective therapy. The main problem with FDG-PET remains the difficulty in defining thresholds for response, as there is clearly a lack in large prospective randomized studies validating the use of FDG-PET in response guidelines.We give an overview of data on response prediction in solid tumours by the application of PET.	esophagus
Human leukocyte antigen-G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma.	Human leukocyte antigen (HLA)-G inhibits functions of immune component cells and promotes malignant cells evading from antitumor immunity. We investigated the clinical relevance of HLA-G expression in esophageal squamous cell carcinoma (ESCC). In our study, HLA-G expression in 79 primary ESCC lesions and corresponding adjacent normal tissues were analyzed with immunohistochemistry. Soluble HLA-G (sHLA-G) in plasma was detected with enzyme-linked immunosorbent assay (ELISA) in 41 ESCC patients (including 19 case-matched lesions and plasma samples) and in 153 normal healthy controls. HLA-G expression was observed in 65.8% (52/79) of the ESCC lesions but not in adjacent normal esophageal tissues. HLA-G expression was more frequently observed in patients with advanced disease stage (III/IV vs. I/II, p = 0.01). Patients with HLA-G expression had a significantly worse survival, and HLA-G could be an independent prognostic factor. sHLA-G levels in plasma were significantly increased in patients compared to normal controls (median: 152.4 U/ml vs. 8.9 U/ml, p < 0.001). The area under receiver-operating characteristic (ROC) curve for sHLA-G in plasma was 0.992. However, no significant correlation was found between sHLA-G in plasma and clinical parameters studied. In conclusion, our findings indicated that HLA-G expression in ESCC is associated with poor survival and could be a prognostic indicator. Furthermore, increased levels of sHLA-G in plasma might be a useful preoperative biomarker for diagnosis.	esophagus
A Western single-center experience with endoscopic submucosal dissection for early gastrointestinal cancers.	Endoscopic submucosal dissection (ESD) has gained worldwide acceptance as a treatment for early gastrointestinal cancers (EGICs). However, the management of these tumors in the Western world is still mainly surgical. Our aim was to evaluate the safety and feasibility of ESD at a European center. Based on the knowledge transferred by one of the most experienced Japanese institutions, we conducted a pilot study on 25 consecutive patients with EGICs located in the esophagus (n = 3), stomach (n = 7), duodenum (n = 1), and colon (n = 14) at our tertiary center over a 2-year-period. The main outcome measurements were complete (R0) resection, as well as en-bloc resection and the management of complications. The R0 and en-bloc resection rates were 100% and 84%, respectively. There were three cases of bleeding and five cases of perforation. With a median follow up of 18 months, two recurrences were observed. We conclude that ESD for early esophageal and gastric cancers is feasible and effective, while colonic ESD requires more expertise.	esophagus
Esophageal cancer dose escalation using a simultaneous integrated boost technique.	PURPOSE: We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. METHODS AND MATERIALS: Treatment plans were generated using four different approaches (two-dimensional conformal radiotherapy [2D-CRT] to 50.4 Gy, 2D-CRT to 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. RESULTS: The 50.4 Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4 Gy 2D-CRT plan. The 64.8 Gy SIB-IMRT plan produced a 28% increase in GTV dose and comparable normal tissue doses as the 50.4 Gy IMRT plan; compared with the 50.4 Gy 2D-CRT plan, the 64.8 Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). CONCLUSIONS: The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation.	esophagus
[Promoting effect of all-trans retinoic acid on the chemosensitivity of esophageal cancer EC9706 cells].	OBJECTIVE: To investigate the impact of all-trans retinoic acid (ATRA) on chemosensitivity to esophageal squamous cell carcinoma EC9706 cells in vitro and its mechanism. METHODS: EC9706 cells were routinely cultured as the control group. The experimental group was divided into three groups. The ATRA group with ATRA in final concentration of 1 µmol/L; the 5-Fu group with 5-Fu in final concentration of 50 mg/L; the combined treatment group with ATRA in final concentration of 1 µmol/L and 5-Fu 50 mg/L. The cell apoptosis was detected by terminal deoxynucleotidy transferase mediated dUTP nick end labelling (TUNEL). The cell cycle and apoptosis were detected by flow cytometry. RESULTS: The results of TUNEL showed that in the combined treatment group appeared a large number of apoptotic cells, and their nuclei were stained brown, with a positive rate of 89.7%. There was a significant difference in the comparison with the ATRA group (38.3%) and 5-Fu group (40.3%) (P < 0.05). The flow cytometry showed that the ATRA + 5-Fu group had a significantly higher apoptosis rate (76.9% ± 2.7%) than that in the ATRA group (38.2% ± 2.6%) and 5-Fu group (45.2% ± 2.3%) (P < 0.05). The ratio of cells in G(1) phase increased in the ATRA + 5-Fu group (83.4% ± 3.0%), significantly higher than (48.2% ± 2.5%) in the ATRA group and (53.2% ± 2.6%) in the 5-Fu group (P < 0.05). The ratio of cells in S + G(2)/M phase was decreased in the ATRA + 5-Fu group, with a significant difference (P < 0.05) when compared with other groups. There was no significant difference between the ATRA group and 5-Fu group (P > 0.05) in the apoptosis rate and the proportion of cells at different phases. CONCLUSION: ATRA can induce apoptosis of esophageal carcinoma EC9706 cells in vitro. The combination of ATRA and 5-Fu may enhance the chemotherapeutic efficacy.	esophagus
The prevalence of lymph node metastases in patients with T1 esophageal adenocarcinoma a retrospective review of esophagectomy specimens.	"Knowledge of the risk of lymph node metastases is critical to planning therapy for T1 esophageal adenocarcinoma. This study retrospectively reviews 75 T1a and 51 T1b tumors and correlates lymph node metastases with depth of tumor invasion, tumor size, presence of lymphovascular invasion, and tumor grade. OBJECTIVES: Increasingly, patients with superficial esophageal adenocarcinoma are being treated endoscopically or with limited surgical resection techniques. Since no lymph nodes are removed with these therapies, it is critical to have a clear understanding of the risk of lymph node metastases in these patients. The aim of this study was to define the risk of lymph node metastases for intramucosal and submucosal (T1) esophageal adenocarcinoma and to analyze factors potentially associated with an increased risk of lymph node involvement. METHODS: We reanalyzed the pathology specimens of all patients that had primary esophagectomy for T1 adenocarcinoma of the distal esophagus or gastroesophageal junction from January 1985 to December 2008. The prevalence of lymph node metastases was correlated with tumor size, depth of invasion, presence of lymphovascular invasion, and degree of tumor differentiation. RESULTS: There were 126 patients, 102 men (81%) and 24 women (19%), with a mean age of 64 (± 10) years. Tumor invasion was limited to the mucosa (T1a) in 75 patients (60%), whereas submucosal invasion (T1b) was present in 51 patients (40%). Tumors that had poor differentiation, lymphovascular invasion, and size ≥2 cm were significantly more likely to be invasive into the submucosa. Lymph node metastases were rare (1.3%) with intramucosal tumors but increased significantly with submucosal tumor invasion (22%)[P = 0.0003]. Lymph node metastases were also significantly associated with poor differentiation (P = 0.0015), lymphovascular invasion (P < 0.0001), and tumor size ≥2 cm (P = 0.01). Division of the submucosa into thirds did not show a layer with a significantly decreased prevalence of node metastases. CONCLUSIONS: Adenocarcinoma invasive deeper than the muscularis mucosa is associated with a significant increase in the prevalence of lymph node metastases,and there is no ""safe"" level of invasion into the submucosa. Lymphovascular invasion, tumor size ≥2 cm, and poor differentiation are associated with an increased risk of submucosal invasion and lymph node metastases and should be factored into the decision for endoscopic therapy or esophagectomy"	esophagus
Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study.	BACKGROUND: Cetuximab plus irinotecan/folinic acid/5-fluorouracil (5-FU) (IF) was evaluated as first-line treatment of patients with advanced gastric cancer and gastroesophageal junction tumors. Preplanned analyses of the influence of tumor biomarkers on treatment outcome were carried out. PATIENTS AND METHODS: Patients received weekly cetuximab (400 mg/m(2) on day 1, subsequently 250 mg/m(2)) plus irinotecan (80 mg/m(2)) and a 24-hour continuous infusion of folinic acid (200 mg/m(2)) and 5-FU (1500 mg/m(2)) on days 1, 8, 15, 22, 29 and 36 of a 50-day cycle, until progressive disease (PD). RESULTS: The most common grade 3/4 toxic effects in 49 patients were diarrhea (15%) and skin toxic effects (14%). In 48 assessable patients, the overall response rate was 46% and disease control rate was 79%. Median progression-free survival (PFS) and overall survival (OS) was 9.0 months [95% confidence interval (CI) 7.1-15.6] and 16.5 months (95% CI 11.7-30.1), respectively. Tumor response was more common than nonresponse in epidermal growth factor receptor-expressing tumors (P = 0.041). Tumor PTEN expression was associated with longer PFS (P = 0.035) and OS (P = 0.0127) than no PTEN expression. CONCLUSION: Cetuximab plus IF was well tolerated and efficacy data were encouraging. This treatment combination and the role of selected biomarkers are under investigation in the ongoing phase III EXPAND trial.	esophagus