crossing96/oncoscreening huggingface dataset:
Clinical predictors of early cancer-related mortality following neoadjuvant therapy and oesophagectomy.	OBJECTIVES: Although oesophagectomy can be curative for patients with oesophageal cancer (OC), it may be associated with high morbidity and decreased quality of life. Identifying risk factors for early systemic progression or death after oesophagectomy may help to guide treatment choices in at-risk patients. METHODS: Patients undergoing oesophagectomy following neoadjuvant therapy for OC (November 1987 to January 2013) were reviewed, excluding deaths ≤3 months. Univariate predictors of death ≤1 year of operation were explored by logistic regression. Significant predictors (P ≤ 0.10) were included in a multivariate model. A risk factor index was created based on the number of significant risk factors in individual patients. RESULTS: Of 581 patients, 238 had neoadjuvant chemotherapy or chemotherapy and radiation followed by oesophagectomy. Of these, 15% (n = 36) died ≤1 year following oesophagectomy and 69% of those from documented cancer recurrence. Clinical predictors of death ≤1 year by multivariate analysis included performance status >0 (HR 2.19; CI 1.02-4.69), poor (G3) tumour differentiation (HR 2.67; CI 1.14-6.21) and lack of clinical response (no response or progression versus complete and partial response) to neoadjuvant therapy (HR 2.77; CI 1.07-7.15). For patients with all factors evaluable (n = 167), variables were summed to derive a cumulative risk factor index, 0-3. An increased risk factor index (≥2) was highly associated with increased risk of death ≤1 year postoperatively (HR 4.84; CI 1.93-12.16), as well as with poor overall survival. CONCLUSIONS: Clinically defined risk factors that predict early mortality following oesophagectomy include performance status, poor tumour differentiation and clinical response. In patients with at least two of these risk factors, 29% will die within 1 year of surgery. These patients should be identified and individual consideration given to less morbid surgical strategies or to alternative treatments.	esophagus
Validation of a new approach for mortality risk assessment in oesophagectomy for cancer based on age- and gender-corrected body mass index.	OBJECTIVES: We developed a new algorithm to identify high-risk patients for underweight after oesophagectomy for cancer. Patients were assigned to an age-gender-specific body mass index percentile (AG-BMI) which is then used in a survival analysis. This model was able to identify patients more at risk for being underweight in comparison with the classically used BMI. It shows a worse overall survival (OS) in patients with a preoperative AG-BMI < 10th percentile. The aim of this study is to validate this new model based on a cohort of patients from an external high-volume institution specialized in oesophageal cancer surgery. METHODS: The validation cohort consists of 407 patients operated on between 1999 and 2012 with the prerequisite data to calculate AG-BMI and OS. The base cohort consisted of 642 consecutive patients, operated on in our institution between 2005 and 2010. Age, gender, height and weight on the day before surgery were used to calculate the BMI and the AG-BMI. OS was analysed and a multivariate analysis was performed. RESULTS: Incidence rates of the AG-BMI < 10th percentile risk-patients in the validation cohort showed similar results to our original results (17.8 vs 17.2% for the base cohort) with a similar significant OS difference between at-risk patients and not-at-risk patients (P < 0.001). Multivariate analysis found the same five independent prognosticators for OS in both datasets: age, early versus advanced disease, resection status, number of positive lymph nodes and the AG-BMI 10th percentile, but not BMI itself. In the validation cohort, gender was identified as an additional independent prognosticator. The worse OS survival in AG-BMI < 10th percentile in both patient populations was related to a significantly higher number of deaths without oesophageal cancer recurrence. CONCLUSIONS: This study validates the newly developed AG-BMI model to predict more accurately a subgroup of patients at risk for worse survival after oesophagectomy. Improved perioperative identification of risk factors for poorer OS could help to develop perioperative strategies to reduce these risks.	esophagus
Angiopoietin-Like Protein 2 Acts as a Novel Biomarker for Diagnosis and Prognosis in Patients with Esophageal Cancer.	BACKGROUND: Angiopoietin-like protein 2 (ANGPTL2) mediates chronic inflammation. Tumor cell-derived ANGPTL2 promotes tumor invasion and angiogenesis. Overexpression of ANGPTL2 in tumor cells is associated with tumor progression and has been recognized in lung, breast, colon, and gastric cancer. However, to our knowledge the functional and clinical significance of ANGPTL2 expression has not been investigated in patients with esophageal cancer (EC). METHODS: First, in vitro assays were performed for functional analysis of ANGPTL2 using small interfering RNA. Next, ANGPTL2 expression in EC tissues (n = 71) was evaluated by immunohistochemistry (IHC in patients with EC (n = 71). Finally, serum ANGPLT2 levels from patients with EC (n = 71) and healthy controls (n = 35) were evaluated using enzyme-linked immunosorbent assay. RESULTS: Knockdown of ANGPTL2 expression decreased the proliferative, invasive, and migration capacity in EC cell lines. ANGPTL2 expression in EC tissues was significantly elevated in patients with a high T stage, squamous cell carcinoma, and high TNM stage. Patients with high ANGPTL2 expression had significantly poorer overall and disease-free survival than those with low expression. Furthermore, high ANGPTL2 expression in EC tissues was an independent predictive marker for a poor prognosis. On the other hand, the serum ANGPTL2 level in patients with EC was significantly higher than that in healthy controls, and allowed for highly accurate discrimination between patients with and without EC. However, no significant association between serum ANGPTL2 levels and clinicopathological findings was observed in patients with EC. CONCLUSIONS: We have demonstrated novel evidence for the clinical significance of ANGPTL2 as a biomarker in patients with EC.	esophagus
Inhibition of heat shock protein 90 suppresses squamous carcinogenic progression in a mouse model of esophageal cancer.	PURPOSE: Heat shock protein 90 (Hsp90), a potential therapeutic target, has been widely recognized in vitro and in vivo in immunodeficient mice. Here, we aimed to evaluate the role of Hsp90 in an immunocompetent mouse model of esophageal squamous cell cancer (ESCC). METHODS: The carcinogen 4-nitroquinoline 1-oxide (4NQO) was used to induce ESCC in C57BL/6 mice. Cancer progression was analyzed through observation of appearance, hematoxylin-eosin staining, immunohistochemical detection, and terminal dUTP nick-end labeling analysis. RESULTS: 4NQO led to the progressive appearance of preneoplastic and tumoral lesions in the esophagus, with 100 % incidence of ESCC in situ occurring only after 16 weeks of carcinogen exposure. Most of these lesions evolved spontaneously into highly invasive ESCC even after 4NQO withdrawal (weeks 16-22). Interestingly, there was marked upregulation of Hsp90 and its client proteins in tumoral lesions at 22 weeks. Hsp90 inhibition by intraperitoneal injection of SNX-2112 over the following 2 weeks downregulated AKT and cyclin D1 expression, leading to significant reduction in tumor incidence and prevention of ESCC progression. Moreover, SNX-2112 treatment decreased proliferating cell nuclear antigen expression and increased the number of apoptotic cells in ESCC tissues. CONCLUSIONS: Our in vivo findings support the contribution of Hsp90 to ESCC progression, which was achieved by stimulating apoptosis and inhibition of cell proliferation, and provide a strong rationale for further evaluation of Hsp90 inhibitors for treating ESCC.	esophagus
Locally advanced gastroesophageal junction tumor: a treatment dilemma.	Over the last several decades, the incidence of adenocarcinoma of the gastroesophageal junction (GEJ) has been increasing in developed countries. Although complete surgical resection remains the cornerstone of treatment for resectable disease, long-term outcomes are poor and recurrence rates are high with surgery alone in patients presenting with locally advanced disease. Multimodal therapy has been shown to improve survival; however, the optimal therapeutic approach remains controversial, and practices vary across the world. Preoperative chemoradiotherapy is generally used in the U.S., whereas perioperative chemotherapy without radiation is favored in most European countries. In this review, we discuss why the treatment of locally advanced GEJ tumors remains controversial, examine the evidence for various multimodal approaches, discuss their respective pros and cons, evaluate the role of radiation therapy, highlight some ongoing and planned clinical trials, and suggest areas that need further research.	esophagus
Occupation and risk of oesophageal adenocarcinoma and squamous-cell carcinoma: The Nordic Occupational Cancer Study.	To assess associations between occupation and risk of oesophageal adenocarcinoma (AC) and squamous-cell carcinoma (SCC), data from the Nordic Occupational Cancer Study, a large population-based cohort with long-term follow-up, was used. The Nordic Occupational Cancer Study includes 12.9 million individuals aged 30-64 years who participated in national censuses in Finland, Iceland, Norway and Sweden in 1960-1990. Individuals were assigned to one of the 54 occupational categories, and individuals with oesophageal cancer were identified through nationwide cancer registries with follow-up through 2005. Country-specific standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) were estimated. During follow-up, 4,722 ACs and 14,496 SCCs were observed. Among men, increased risks of AC and SCC were observed among waiters (SIR = 2.58, 95% CI 1.41-4.32 and SIR = 3.22, 95% CI 2.30-4.38 for AC and SCC, respectively), cooks and stewards (1.72, 1.04-2.69 and 2.53, 1.94-3.25), seamen (1.52, 1.16-1.95 and 1.77, 1.53-2.05), food workers (1.51, 1.18-1.90 and 1.21, 1.03-1.42), miscellaneous construction workers (1.24, 1.04-1.48 and 1.39, 1.25-1.54) and drivers (1.16, 1.01-1.33 and 1.23, 1.13-1.34). Decreased risks of AC and SCC were observed among technical workers, physicians, teachers, religious workers and gardeners. The SIR for AC was significantly different from that for SCC in six occupational categories. Among women, increased risks among food workers and waiters and decreased risks among teachers, nurses and assistant nurses were observed for SCC only. In both sexes, increased risks were observed among waiters and food workers, and decreased risks were observed among teachers. This large cohort study indicates that the risk of oesophageal cancer varies by occupation, but not by histological type in most occupational categories.	esophagus
Esophageal cancer in a family with hamartomatous tumors and germline PTEN frameshift and SMAD7 missense mutations.	Germline mutations in the PTEN tumor-suppressor gene cause autosomal-dominant conditions such as Cowden and Bannayan-Riley-Ruvalcaba syndromes with variable presentations, including hamartomatous gastrointestinal tumors, dermatologic abnormalities, neurologic symptoms, and elevated cancer risk. We describe a father and son with extensive hamartomatous gastrointestinal polyposis who both developed early-onset esophageal cancer. Exome sequencing identified a novel germline PTEN frameshift mutation (c.568_569insC, p.V191Sfs*11). In addition, a missense mutation of SMAD7 (c.115G>A, p.G39R) with an allele frequency of 0.3% in the Exome Variant Server was detected in both affected individuals. Fluorescence in situ hybridization for PTEN in the resected esophageal cancer specimen demonstrated no PTEN copy loss in malignant cells; however, results of an immunohistochemical analysis demonstrated a loss of PTEN protein expression. While the risks of many cancers are elevated in the PTEN hamartoma tumor syndromes, association between esophageal adenocarcinoma and these syndromes has not been previously reported. Esophageal adenocarcinoma and extensive polyposis/ganglioneuromatosis could represent less common features of these syndromes, potentially correlating with this novel PTEN frameshift and early protein termination genotype. Alternatively, because simultaneous disruption of both the PTEN and TGF-β/SMAD4 pathways is associated with development of esophageal cancer in a mouse model and because SMAD4 mutations cause gastrointestinal hamartomas in juvenile polyposis syndrome, the SMAD7 mutation may represent an additional modifier of these individuals' PTEN-mutant phenotype.	esophagus
Is cardiac toxicity a relevant issue in the radiation treatment of esophageal cancer?	PURPOSE: In recent years several papers have been published on radiation-induced cardiac toxicity, especially in breast cancer patients. However, in esophageal cancer patients the radiation dose to the heart is usually markedly higher. To determine whether radiation-induced cardiac toxicity is also a relevant issue for this group, we conducted a review of the current literature. METHODS: A literature search was performed in Medline for papers concerning cardiac toxicity in esophageal cancer patients treated with radiotherapy with or without chemotherapy. RESULTS: The overall crude incidence of symptomatic cardiac toxicity was as high as 10.8%. Toxicities corresponded with several dose-volume parameters of the heart. The most frequently reported complications were pericardial effusion, ischemic heart disease and heart failure. CONCLUSION: Cardiac toxicity is a relevant issue in the treatment of esophageal cancer. However, valid Normal Tissue Complication Probability models for esophageal cancer are not available at present.	esophagus
Effect of Neoadjuvant Radiation Dose on Surgical and Oncological Outcome in Locally Advanced Esophageal Cancer.	INTRODUCTION: Neoadjuvant chemoradiation (CRT) confers a survival benefit in locally advanced esophageal cancer. The optimal dose of radiotherapy remains undefined. METHODS: From a prospective database, we identified patients who received CRT followed by Ivor Lewis esophagectomy. Surgical complications, pathological response, and oncological outcome were compared between patients who received a radiotherapy (RT) dose of 36 Gy (group1) versus a dose of > 40 Gy (group 1). RESULTS: 147 patients were evaluated: 109 received 36 Gy, while 38 received 41-50Gy. Mean age was 61 ± 9 years (84% male). Median hospital stay was 16 days. Anastomotic leakage occurred in 4.0%. Pulmonary complications occurred in 41.8%, neither being influenced by RT dose. Complete resection (R0) was achieved in 95% (group 1) and 100% (group 2), P = 0.3. Pathological complete response (pCR) was observed in 19% (group 1) and 37% (group 1), P = 0.04. Local recurrence developed in 9% in group 1, and 3% in group 2 (P = 0.3), but regional recurrence developed significantly higher in the low dose group (18% vs 3%, P < 0.001). Metastatic recurrence occurred in 48% in group 1 and 13% in group 1 (P < 0.001). CONCLUSIONS: In patients with locally advanced esophageal cancer a higher RT dose does not affect surgical outcome, enhances pCR rate, and reduces the locoregional and metastatic recurrence risk.	esophagus
MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance.	BACKGROUND: Carcinoma of the esophagus has a high case fatality ratio and is now the 6th most common cause of cancer deaths in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC) pre and post induction therapy. Of the miRNAs differentially expressed post induction chemoradiation, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold following induction therapy, however, its expression was associated with shorter disease-free survival. This unexpected result was explored in this current study. METHODS: In order to study the role of miR-145 in EAC, miRNA-145 was overexpressed in 3 EAC cell lines (OE33, FLO-1, SK-GT-4) and one ESCC cell line (KYSE-410). After validation of the expression of miR-145, hallmarks of cancer such as cell proliferation, resistance to chemotherapy drugs or anoikis, and cell invasion were analyzed. RESULTS: There were no differences in cell proliferation and 5 FU resistance between miR145 cell lines and the control cell lines. miR-145 expression also had no effect on cisplatin resistance in two of three cell lines (OE33 and FLO-1), but miR-145 appeared to protect SK-GT-4 cells against cisplatin treatment. However, there was a significant difference in cell invasion, cell adhesion and resistance to anoikis. All three EAC miR-145 cell lines invaded more than their respective controls. Similarly, OE33 and SK-GT-4 miR-145 cell lines were able to survive longer in a suspension state. DISCUSSION: While expression of miR-145 in ESCC stopped proliferation and invasion, expression of miR-145 in EAC cells enhanced invasion and anoikis resistance. Although more work is required to understand how miR-145 conveys these effects, expression of miR-145 appears to promote EAC progression by enhancing invasion and protection against anoikis, which could in turn facilitate distant metastasis.	esophagus
Primary malignant melanoma of esophagus: a case report and review of literature.	Primary malignant melanoma of esophagus is a rare but highly aggressive neoplasm, with an incidence less than 0.2% of all primary esophagus neoplasms. There are no clinical differences from other forms of esophagus cancer. Because initial symptoms are nonspecific, the patients are usually diagnosed at a late stage. The prognosis is poor, and curative effect seems disappointed. Several reports suggest that most of patients die from distant metastases, and the 5-year survival rate is approximately 4.2%. This case report includes a review of the surgical pathology, clinical features and treatment of primary malignant melanoma of esophagus. This case report presents a 56-year-old female with primary malignant melanoma of esophagus, treated by surgical resection. Till now, the patient is still alive for 5 months without any chemotherapy, radiotherapy and immunomodulatory therapy.	esophagus
Aquaporin-8 mediates human esophageal cancer Eca-109 cell migration via the EGFR-Erk1/2 pathway.	Abnormal expression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases1/2 (ERK1/2) are associated with tumorigenesis and cancer progression and may upregulate AQPs expression. In this study, we investigated acquaporin-8 expression and signaling via epidermal growth factor receptor-extracellular signal-regulated kinases1/2 in human esophageal cancer Eca-109 cells by western blot, immunofluorescence and wound healing (scratch) assays. Our results showed that epidermal growth factor (EGF) induced both Eca-109 migration and AQP8 expression. Wound healing results showed that cell migration was increased by 1.23-1.10-fold at 24 h and 48 h after EGF treatment. AQP8 expression was significantly increased (1.19-fold) at 48 h after EGF treatment in Eca-109. The EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 3.65-fold (EGF-treated) to 0.55-fold (PD153035-treated) in Eca-109. Furthermore, the MEK [MAPK (mitogen-activated protein kinase)/Erk1/2]/Erk1/2 inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 3.92-fold (EGF-treated) to 1.38-fold (U0126-treated) in Eca-109. In conclusions, EGF induces AQP8 expression and cell migration in Eca-109 cells via the EGFR/Erk1/2 signal transduction pathway.	esophagus
Cardiac tamponade due to bleeding as a potential lethal complication after surgery for esophageal cancer.	BACKGROUND: Cardiac tamponade, due to bleeding in the pericardial space after esophagectomy for esophageal cancer, is an extremely rare complication and may be associated with sudden hemodynamic instability that can lead to death unless there is prompt diagnosis and appropriate treatment. CASE REPORT: A 76-year-old man underwent sub-total esophagectomy via a cervico-right thoracoabdominal approach and reconstruction with a gastric tube through the retrosternal route. On postoperative day 4, the patient developed hypotension due to cardiac tamponade caused by bleeding into the pericardial space and he had a decreased level of consciousness. Pericardial resection and open drainage via a minimal left anterior thoracotomy was performed that resulted in hemodynamic improvement followed by an uneventful recovery. CONCLUSION: Cardiac tamponade due to postoperative bleeding, which is a rare but life-threatening complication, should be considered as a cause of hemodynamic instability in the early postoperative period after esophagectomy.	esophagus
Effect of bilateral supraclavicular postoperative radiotherapy in middle and lower thoracic esophageal carcinoma.	AIM: To evaluate whether postoperative radiotherapy is an alternative to neck lymph node surgery and if it provides a survival benefit for those receiving two-field, chest and abdomen, lymphadenectomy. METHODS: A total of 530 cases with middle and lower thoracic esophageal carcinoma in our hospital from January 2008 to April 2009 were selected and analyzed, of which 219 cases received right chest, upper abdominal incision Ivor-Lewis surgery and simultaneously underwent mediastinal and abdominal two-field lymphadenectomy. If regional lymph node metastasis occurred within the recurrent laryngeal nerve, the patients would receive bilateral supraclavicular radiotherapy (DT = 5000cGy) to be adopted at postoperative 4-5 wk (Group A) or cervical lymphadenectomy at postoperative 3-4 wk (Group B). If there were no regional lymph node metastases within the recurrent laryngeal nerve, the patients only underwent two-field, chest and abdomen, lymphadenectomy (Group C). RESULTS: In 219 cases who underwent two-field lymphadenectomy, 91 cases were diagnosed with regional lymph node metastasis within the recurrent laryngeal nerve. Of them, 48 cases received cervical radiotherapy, and 43 cases underwent staging lymphadenectomy; 128 patients were not given the follow-up treatment of cervical radiotherapy because there was no regional lymph node metastasis within the recurrent laryngeal nerve. Five-year survival rates in group A and B were 47% and 50%, respectively, with no statistical difference between them, and the rate in group C was 58%. CONCLUSION: For patients with middle and lower thoracic esophageal carcinoma combined with lymph node metastasis within the recurrent laryngeal nerve, cervical radiotherapy can be a substitute for surgery and provide benefit.	esophagus