crossing96/oncoscreening huggingface dataset:
The Progression of Esophageal Mucosa-associated Lymphoid Tissue Lymphoma after Helicobacter pylori Eradication Therapy: A Case Report and Discussion of Therapeutic Options.	A 50-year-old woman with epigastric discomfort was referred to our hospital. Esophagogastroduodenoscopy showed flat, elevated, submucosal tumor-like lesions in the esophagus. Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) of the esophagus was diagnosed based on the examination of an endoscopic biopsy specimen. Computed tomography showed the enlargement of a lymph node in the gastric cardia. The present case showed disease progression despite Helicobacter pylori eradication therapy and achieved partial remission after rituximab monotherapy. The patient remained in partial remission for 20 months. This case suggests that esophageal MALT lymphoma with lymph node involvement does not respond to H. pylori eradication therapy and that it requires systemic treatment.	esophagus
Predicting lymph node metastasis for endoscopic resection of superficial esophageal squamous cell carcinoma.	OBJECTIVE: The aims of this study were to identify risk factors for lymph node metastasis and develop a reliable risk stratification system. METHODS: Between May 2001 and December 2015, 262 patients who underwent endoscopic resection or surgery for superficial esophageal squamous cell carcinoma were enrolled. We evaluated possible predictive factors for lymph node metastasis: age, gender, tumor length, tumor area, circumferential spread, tumor location, gross appearance, depth of invasion, tumor differentiation, and lymphovascular invasion. RESULTS: The incidence of lymph node metastasis was 14.5% (38/262). In multivariate analysis, tumor size (>15 mm), depth of invasion (submucosal invasion), and lymphovascular invasion were significantly associated with lymph node metastasis. These factors were included in the risk stratification system and assigned scores; the total risk stratification system score was 0 to 6. The area under the receiver operating characteristic curve for predicting lymph node metastasis was 0.869 (95% confidence interval, 0.813-0.926). The high-risk group (risk stratification system score ≥3) exhibited a significantly higher risk of lymph node metastasis than the low-risk group (score <3) (26.5% vs 1.6%). There was no lymph node metastasis in patients with a risk stratification system of 0. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the risk stratification system were 94.7%, 55.4%, 26.5%, 98.4%, and 61.1%, respectively. CONCLUSIONS: We developed a risk stratification system that should facilitate the identification of patients with a high or low risk of lymph node metastasis. This may aid the precise selection of patients who can undergo endoscopic resection.	esophagus
Serial Endoscopic Evaluation of Esophageal Disease in a Cancer Model: A Paradigm Shift for Esophageal Adenocarcinoma (EAC) Drug Discovery and Development.	A rat model of surgically induced reflux recapitulates the development and progression of human esophageal adenocarcinoma (EAC). In this study, reflux was induced in rats followed by postoperative endoscopy with biopsy, to diagnose and monitor disease progression. Overall, percentage agreement between visual endoscopy and gold standard histology was 95%, with disease-specific classification accuracies of 100% and 75% for Barrett's with dysplasia and EAC, respectively. Additionally, the percentage agreement for biopsy in tumors >4 mm was 75%. Thereby, establishing endoscopic evaluation as a reliable tool to assess disease progression and provide biopsies for downstream correlates in a de novo EAC model.	esophagus
RUNX2 Plays An Oncogenic Role in Esophageal Carcinoma by Activating the PI3K/AKT and ERK Signaling Pathways.	BACKGROUND/AIMS: Esophageal carcinoma is a frequently occurring cancer at upper gastrointestinal tract. We aimed to evaluate the roles and possible mechanism of Runt Related Transcription Factor 2 (RUNX2) in the development of esophageal cancer. METHODS: The expression of RUNX2 in esophageal carcinoma tissues and cells was investigated by qRT-PCR. Effects of RUNX2 on cell viability, apoptosis, migration and invasion were assessed using MTT assay, flow cytometry assay/western blot analysis, and Transwell assays, respectively. Afterwards, effects of RUNX2 on of the activation of the PI3K/AKT and ERK pathways were explored by Western blot analysis. In addition, a PI3K/AKT pathway inhibitor LY294002 and an ERK inhibitor U0126 were applied to further verify the regulatory relationship between RUNX2 and the PI3K/AKT and ERK signaling pathways. Besides, the RUNX2 function on tumor formation in vivo was investigated by tumor xenograft experiment. RESULTS: The result showed that RUNX2 was highly expressed in esophageal carcinoma tissues and cells. Knockdown of RUNX2 significantly inhibited TE-1 and EC-109 cell viability, repressed TE-1 cell migration and invasion, and increased TE-1 cell apoptosis. RUNX2 overexpression showed the opposite effects on HET-1A cells. Moreover, RUNX2-mediated TE-1 cell viability, migration and invasion were associated with the activation of the PI3K/AKT and ERK pathways. Besides, knockdown of RUNX2 markedly suppressed tumor formation in vivo. CONCLUSION: Our results indicate that RUNX2 may play an oncogenic role in esophageal carcinoma by activating the PI3K/ AKT and ERK pathways. RUNX2 may serve as a potent target for the treatment of esophageal carcinoma.	esophagus
Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or the gastroesophageal junction: A meta-analysis based on clinical trials.	BACKGROUND: The benefit of neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy for treating cancer of the esophagus or the gastroesophageal junction remains controversial. In the present study, we conducted a comprehensive meta-analysis to examine the efficacy of these two management strategies. METHODS: The MEDLINE (PubMed), SinoMed, Embase, and Cochrane Library databases were searched for eligible studies. We searched for the most relevant studies published until the end of September 2017. Data were extracted independently and were analyzed using RevMan statistical software version 5.3 (Cochrane Collaboration, http://tech.cochrane.org/revman/download). Weighted mean differences, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's risk of bias tool was used to assess the risk of bias. In this comprehensive meta-analysis, we examined the efficiency of neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy for the treatment of cancer of the esophagus or the gastroesophageal junction as reported in qualified clinical trials. RESULTS: Six qualified articles that included a total of 866 patients were identified. The meta-analysis showed that for 3-year and 5-year survival rates in primary outcomes, the results favored neoadjuvant chemoradiotherapy strategies compared with neoadjuvant chemotherapy (RR = 0.78, 95% CI = 0.62-0.98, P = 0.03; RR = 0.69, 95% CI = 0.50-0.96, P = 0.03, respectively). In terms of secondary outcomes, neoadjuvant chemoradiotherapy significantly increased the rate of R0 resection and pathological complete response as well (RR = 0.87, 95% CI = 0.81-0.92, P < 0.0001; RR = 0.16, 95% CI = 0.09-0.28, P < 0.00001, respectively). However, there were no significant differences in postoperative mortality between the two groups (RR = 1.85, 95% CI = 0.93-3.65, P = 0.08). For the results of postoperative complications, revealed that there was a statistically significant difference between the two groups in the incidence of postoperative complications such as pulmonary, anastomotic leak and cardiovascular complications. The subgroup analysis of patients with esophageal adenocarcinoma or squamous cell carcinoma showed that both esophageal adenocarcinoma and squamous cell carcinoma patients achieved a high rate of R0 resection (RR = 0.85, 95% CI = 0.77-0.93, P = 0.0006; RR = 0.88, 95% CI = 0.81-0.96, P = 0.005, respectively) and pathological complete response benefit of neoadjuvant chemoradiotherapy (RR = 0.23, 95% CI = 0.09-0.57, P = 0.001; RR = 0.18, 95% CI = 0.03-0.96, P = 0.05, respectively). CONCLUSION: Our findings suggested that compared with neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy should be recommended with a significant long-term survival benefit in patients with cancer of the esophagus or the gastroesophageal junction. In view of the clinical heterogeneity, whether these conclusions are broadly applicable should be further determined.	esophagus
Increased miR-203-3p and reduced miR-21-5p synergistically inhibit proliferation, migration, and invasion in esophageal cancer cells.	Dysregulation of miR-203-3p and miR-21-5p has been identified in esophageal cancer (EC). The restoration of miR-203-3p and reduction of miR-21-5p were able to cause tumor suppression. Here, co-transfection of miR-203-3p mimics and miR-21-5p inhibitors led to an extraordinary increased expression of miR-203-3p and synergistically inhibited proliferation, migration, and invasion in EC cells. Moreover, we found that Ran GTPase (Ran) was dramatically inhibited in EC cells treated with the co-transfection of miR-203-3p mimics and miR-21-5p inhibitors. Finally, in-vivo studies showed that overexpression of miR-203-3p, combined with the suppression of miR-21-5p, significantly co-inhibited growth of tumors. The obtained data suggested that the development of miRNA-based combination therapeutics represents a promising cancer treatment strategy.	esophagus
Human umbilical vein endothelial cell vaccine suppresses the angiogenesis of esophageal squamous cell carcinoma in a humanized mouse model.	The antitumor effect of the human umbilical vein endothelial cell (HUVEC) vaccine has been well documented; however, its anti‑angiogenic effects on human esophageal squamous cell carcinoma (ESCC) have yet to be studied. In the present study, a 'humanized' mouse model was established by transplanting NOD/SCID mice with human peripheral blood mononuclear cells (PBMC). After 4 weeks, the level of cluster of differentiation (CD)‑45+ human T‑lymphocytes in mouse peripheral blood was >0.1%, which indicated that mouse reconstruction and the human immune system transformation had been successful. The humanized mice were used to evaluate the anti‑angiogenic effect of the HUVEC vaccine on human ESCC. After immunization with the HUVEC vaccine for 5 consecutive weeks, the humanized mice were subcutaneously transplanted with EC9706 cells. The results indicated that the HUVEC vaccine reduced the size of human esophageal carcinoma xenografts by suppressing angiogenesis. In addition, the HUVEC‑immunized mice exhibited reduced expression of angiogenesis‑associated antigens (vascular endothelial growth factor receptor 2 and VE‑Cadherin) in the tumor specimens, and increased levels of angiogenesis‑associated antibodies in the serum. Notably, the HUVEC vaccine also increased the infiltration of human T‑lymphocytes into the spleen of humanized mice. In conclusion, the present study demonstrated the anti‑angiogenic effect of the HUVEC vaccine on ESCC in a humanized mouse model, and set an experimental foundation for the application of the HUVEC vaccine in ESCC patients.	esophagus
The chromosome 11q13.3 amplification associated lymph node metastasis is driven by miR-548k through modulating tumor microenvironment.	BACKGROUND: The prognosis for esophageal squamous cell carcinoma (ESCC) patients with lymph node metastasis (LNM) is still dismal. Elucidation of the LNM associated genomic alteration and underlying molecular mechanisms may provide clinical therapeutic strategies for ESCC treatment. METHODS: Joint analysis of ESCC sequencing data were conducted to comprehensively survey SCNAs and identify driver genes which significantly associated with LNM. The roles of miR-548k in lymphangiogensis and lymphatic metastasis were validated both in vitro and in vivo. ESCC tissue and blood samples were analyzed for association between miR-548k expression and patient clinicopathological features and prognosis and diagnosis. RESULTS: In the pooled cohort of 314 ESCC patients, we found 76 significant focused regions including 43 amplifications and 33 deletions. Clinical implication analysis revealed a panel of genes associated with LNM with the most frequently amplified gene being MIR548K harbored in the 11q13.3 amplicon. Overexpression of miR-548k remarkably promotes lymphangiogenesis and lymphatic metastasis in vitro and in vivo. Furthermore, we demonstrated that miR-548k modulating the tumor microenvironment by promoting VEGFC secretion and stimulating lymphangiogenesis through ADAMTS1/VEGFC/VEGFR3 pathways, while promoting metastasis by regulating KLF10/EGFR axis. Importantly, we found that serum miR-548k and VEGFC of early stage ESCC patients were significantly higher than that in healthy donators, suggesting a promising application of miR-548k and VEGFC as biomarkers in early diagnosis of ESCC. CONCLUSIONS: Our study comprehensively characterized SCNAs in ESCC and highlighted the crucial role of miR-548k in promoting lymphatic metastasis, which might be employed as a new diagnostic and prognostic marker for ESCC.	esophagus
Increased Tim-3(+) T cells in PBMCs during nivolumab therapy correlate with responses and prognosis of advanced esophageal squamous cell carcinoma patients.	The recent development of immune checkpoint inhibitors for many types of cancers has prompted us to identify markers that predict patients with clinical benefits. Several trials on nivolumab for the treatment of esophageal squamous cell carcinoma (ESCC) have been performed worldwide, and the identification of markers specific to ESCC is urgently needed. We conducted a clinical trial on nivolumab for advanced ESCC (JapicCTI-No.142422) and investigated markers using peripheral blood collected from 20 patients enrolled in our institute, including 1 with a complete response (CR), 5 with a partial response (PR), 6 with a stable disease (SD), and 8 with a progressive disease (PD) as clinical responses. The expression of surface molecules and cytokine production by T cells were analyzed using flow cytometry, and clinicopathological factors and general blood parameters were examined. Albumin, neutrophils, %Tim3, %OX40, %CD103, %CD45RA(-)CD27(-), and IL-1b after the first cycle of nivolumab treatment, but not at baseline, distinguished CR/PR from SD/PD patients. When markers to distinguish longer survivors with nivolumab therapy were analyzed, changes in these levels between baseline and after the first cycle of nivolumab treatment, but not levels at each period, were indicative, similar to the tumor burden. Among them, elevations in %Tim-3(+)CD4 had a marked impact on survival rates. In conclusion, dynamic elevations in %Tim-3 in T cells in the early period of nivolumab therapy have potential as a marker for the clinical responses and prognosis of advanced ESCC patients.	esophagus
Current choices and prospects in management of postoperative esophageal cancer patients.	Locally advanced esophageal cancer is usually dealt with multimodal therapies. The current treatment of choice is neoadjuvant chemoradiation with surgery, but several other choices are also available for adenocarcinoma. For example, adjuvant therapy can be added to the patients received upfront surgery or neoadjuvant therapy in certain conditions. However, squamous cell carcinoma has no such flexibility. This article will address the reason to this remarkable difference, also the current evidence and perspective of adjuvant therapy for esophageal squamous cell carcinoma.	esophagus
Long non-coding RNA LINC01617 promotes proliferation and metastasis of esophageal cancer cells through AKT pathway.	OBJECTIVE: To investigate the clinical significance of long non-coding RNA LINC01617 in esophageal cancer and explore the effect of LINC01617 on the proliferation and metastasis of esophageal cancer cells. METHODS: Real time fluorescence PCR was used to detect the expression of LINC01617 in 142 cases of esophageal cancer and adjacent tissues. The relationship between the expression level of LINC01617 and the survival rate of esophageal cancer patients was analyzed. The function of LINC01617 was detected in esophageal cancer cell lines. The tumor growth ability test was carried out in the nude mice. RESULTS: We found that LINC01617 was overexpressed in esophageal cancer, and its expression was associated with poor prognosis of esophageal cancer. In vitro experiments confirmed that knockout of LINC01617 significantly inhibited the proliferation, migration and invasion of esophageal cancer cells. Moreover, knockout of LNC01617 can inhibit the growth of esophageal cancer in nude mice. The Akt pathway may be involved in the regulation of cell activity in esophageal cancer. CONCLUSIONS: LINC01617 may be involved in the occurrence and development of esophageal cancer, suggesting that LINC01617 can be used as a biomarker and potential therapeutic target for esophageal cancer.	esophagus
FDA Approval Summary: Pembrolizumab for Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1.	On September 22, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval for pembrolizumab (Keytruda, Merck & Co., Inc., Whitehouse Station, NJ) for the treatment of patients with recurrent, locally advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after two or more systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy, and whose tumors express programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test. Approval was based on demonstration of durable overall response rate (ORR) in a multicenter, open-label, multicohort trial (KEYNOTE-059/Cohort 1) that enrolled 259 patients with locally advanced or metastatic gastric or GEJ adenocarcinoma. Among the 55% (n = 143) of patients whose tumors expressed PD-L1 based on a combined positive score ≥1 and either were microsatellite stable or had undetermined microsatellite instability or mismatch repair status, the confirmed ORR as determined by blinded independent central review was 13.3% (95% CI, 8.2-20.0); 1.4% had complete responses. Response durations ranged from 2.8+ to 19.4+ months; 11 patients (58%) had response durations of 6 months or longer, and 5 patients (26%) had response durations of 12 months or longer. The most common (≥20%) adverse reactions of pembrolizumab observed in KEYNOTE-059/Cohort 1 were fatigue, decreased appetite, nausea, and constipation. The most frequent (≥2%) serious adverse drug reactions were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. Pembrolizumab was approved concurrently with the PD-L1 immunohistochemistry 22C3 pharmDx test (Dako, Agilent, Santa Clara, CA) for selection of patients with gastric cancer for treatment with pembrolizumab based on PD-L1 tumor expression. IMPLICATIONS FOR PRACTICE: This report presents key information on the basis for Food and Drug Administration approval of pembrolizumab for the treatment of patients with locally advanced or metastatic gastric or GEJ adenocarcinoma whose tumors express PD-L1. The report discusses the basis for limiting the indication to patients with PD-L1-expressing tumors and the basis for recommending that PD-L1 status be assessed using a fresh tumor specimen if PD-L1 expression is not detected in an archival gastric or GEJ cancer specimen.	esophagus
Operative time in esophagectomy: Does it affect outcomes?	BACKGROUND: The effect of operative duration on postoperative outcomes of esophagectomy is not well understood. The relationship between operative duration and postoperative complications was explored. METHODS: Esophagectomies with gastric reconstruction performed between 2010 and 2015 were queried from the National Surgical Quality Improvement Program. Linear and multivariate regression analyses were used to determine if operative duration correlated with outcomes independent of comorbidities. Subset analysis was performed by the type of esophagectomy. RESULTS: There were 5,098 patients with a median age and operative time of 64 years and 353 minutes, respectively. In the transhiatal group, longer operative times correlated with increased rates of pneumonia, prolonged intubation, unplanned reintubation, septic shock, unplanned reoperation, duration of stay, and mortality. For Ivor-Lewis esophagectomy, there were similar correlations with postoperative complications but not mortality. With the McKeown approach, there were no correlations between operative duration and postoperative outcomes. CONCLUSION: Prolonged operative time has an independent adverse impact on postoperative morbidity, which varies by surgical approach. We have identified unique cut points in the operative time for transhiatal (333 minutes) and Ivor-Lewis esophagectomy (422 minutes), which can be used as a prognostic marker for postoperative outcomes as well as a quality metric in well-selected patients.	esophagus
Propensity score analysis of 18-FDG PET/CT-enhanced staging in patients undergoing surgery for esophageal cancer.	PURPOSE: PET/CT is now integral to the staging pathway for potentially curable esophageal cancer (EC), primarily to identify distant metastases undetected by computed tomography. The aim of this study was to analyze the effect of PET/CT introduction on survival and assess patterns of recurrence after esophagectomy. METHODS: A longitudinal cohort of EC patients staged between 1998 and 2016 were considered for inclusion. After co-variate adjustment using propensity scoring, a cohort of 496 patients (273 pre-PET/CT and 223 post-PET/CT) who underwent esophagectomy [median age 63 years (31-80), 395 males, 425 adenocarcinomas, 71 squamous cell carcinomas, 325 neoadjuvant therapy] were included. The primary outcome measure was overall survival (OS) based on intention to treat. RESULTS: Three-year OS pre-PET/CT was 42.5% compared with 57.8% post-PET/CT (Chi(2) 6.571, df 1, p = 0.004). On multivariable analysis, pT stage (HR 1.496 [95% CI 1.28-1.75], p < 0.0001), pN stage (HR 1.114 [95% CI 1.04-1.19], p = 0.001) and PET/CT staging (HR 0.688 [95% CI 0.53-0.89] p = 0.004) were independently associated with OS. Recurrent cancer was observed in 125 patients (51.4%) pre-PET/CT, compared with 74 patients post-PET/CT (37.8%, p = 0.004), and was less likely to be distant recurrence after PET/CT introduction (39.5 vs. 27.0%, p = 0.006). CONCLUSIONS: Enhanced PET/CT staging is an important modality and independent factor associated with improved survival in patients undergoing esophagectomy for cancer.	esophagus