crossing96/oncoscreening huggingface dataset:
Aberrant methylation-mediated downregulation of long noncoding RNA LOC100130476 correlates with malignant progression of esophageal squamous cell carcinoma.	BACKGROUND: Dysregulated long non-coding RNAs (lncRNAs) are involved in many complicated human diseases including cancer. AIMS: To determine the role and methylation status of a new lncRNA LOC100130476 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and twenty three ESCC patients with tumor tissues and corresponding adjacent normal tissues were enrolled. The expression level and methylation status of LOC100130476 in esophageal cancer cell lines and primary ESCC samples were respectively detected. RESULTS: Significant downregulation of LOC100130476 was detected in esophageal cancer cell lines and primary ESCC tumor tissues. Up-regulation of LOC100130476 led to the inhibition of proliferation and invasiveness of the cancer cells. Aberrant hypermethylation of the CpG sites in exon 1 closing to the transcription start site was found to be more tumor-specific and to be more critical for gene silencing. Hypermethylation of these CpG sites was associated with TNM stage and pathological differentiation. ESCC patients in stage III and IV, with low expression or hypermethylation of the CpG sites in exon 1 demonstrated poor patient survival. CONCLUSIONS: LOC100130476 is down-regulated in ESCC at least partly by hypermethylation of CpG sites in exon 1 and its hypermethylation may have prognostic implications for ESCC patients.	esophagus
Optimal Adjuvant Treatment for Curatively Resected Thoracic Esophageal Squamous Cell Carcinoma: A Radiotherapy Perspective.	PURPOSE: The purpose of this study was to evaluate the benefits of adjuvant treatment for curatively resected thoracic esophageal squamous cell carcinoma (ESCC) and determine the optimal adjuvant treatments. MATERIALS AND METHODS: One hundred ninety-five patients who underwent a curative resection for thoracic ESCC between 1994 and 2014 were reviewed retrospectively. Postoperatively, the patients received no adjuvant treatment (no-adjuvant group, n=68), adjuvant chemotherapy (AC group, n=62), radiotherapy (RT group, n=41), or chemoradiotherapy (CRT group, n=24). Chemotherapy comprised cisplatin and 5-fluorouracil administration every 3 weeks. The median RT dose was 45.0 Gy (range, 34.8 to 59.4 Gy). The overall survival (OS), disease-free survival (DFS), locoregional recurrence (LRR), and distant metastasis (DM) rates were estimated. RESULTS: At a median follow-up duration of 42.2 months (range, 6.3 to 215.2 months), the 5-year OS and DFS were 37.6% and 31.4%, respectively. After adjusting for other clinicopathologic variables, the AC and CRT groups had a significantly better OS and DFS compared to the no-adjuvant group (p < 0.05). The LRR rate was significantly lower in the RT and CRT groups than in the no-adjuvant group (p < 0.05), whereas no significant difference was observed in the AC group. In the no-adjuvant and AC groups, 25% of patients received high-dose salvage RT due to LRR. The DM rates were similar. The anastomotic stenosis and leakage were similar in the treatment groups. CONCLUSION: Adjuvant treatment might prolong survival after an ESCC resection, and RT contributes to a reduction of the LRR. Overall, the risks and benefits should be weighed properly when selecting the optimal adjuvant treatment.	esophagus
[Clinical implications of the concentration and EGFR/KRAS mutations of plasma cell free DNA of patients with lung cancer and esophageal cancer].	OBJECTIVE: To analyze the correlation between the concentration of plasma cell free DNA (cfDNA) of patients with lung cancer or esophageal cancer and clinical features, and to assess the coincidence rate of the EGFR/KRAS mutations between the cfDNA and tumor tissue DNA. METHODS: A total of 30 cases lung cancer and esophageal cancer (including 15 lung cancer, 15 esophageal cancer) were enrolled in this study. The tumor tissue and plasma sample of patients were collected. The tumor tissue DNA and plasma cfDNA were extracted. The EGFR/KRAS mutations of the tumor tissue DNA and plasma cfDNA were detected by fluorescence PCR. RESULTS: The concentration of cfDNA of patients with lung cancer (5.0 ± 1.4) μg/L and esophageal cancer (7.0 ± 0.8) μg/L were positively correlated with tumor size (r = 0.574, P = 0.01). There was no significant correlation between the concentration of cfDNA and TNM stage of tumor, gender, and age of patients. There was no EGFR/KRAS gene mutations in tumor tissue DNA and plasma cfDNA of esophageal cancer. A total of 6 tumor tissue samples of lung cancer patients were detected EGFR mutation, and 1 tumor tissue sample was detected KRAS mutation. Meanwhile, 4 plasma cfDNA samples of lung cancer patients were detected EGFR mutation, and 1 plasma cfDNA sample was detected KRAS mutation. CONCLUSION: The concentration of cfDNA of patients with lung cancer and esophageal cancer was positively correlated with tumor burden. There was high coincidence rate of the EGFR/KRAS mutations between the cfDNA and tumor tissue DNA.	esophagus
Endoscopic Resection and Radiofrequency Ablation for Early Esophageal Neoplasia.	In the last few decades, endoscopic treatment of early neoplastic lesions in the esophagus has established itself as a valid and less invasive alternative to surgical resection. Endoscopic resection (ER) is the cornerstone of endoscopic therapy. Next to the curative potential of ER, by removing neoplastic lesions, ER may also serve as a diagnostic tool. The relatively large tissue specimens obtained with ER enable accurate histological staging of a lesion, allowing for optimal decision-making for further patient management. ER was pioneered in Japan, mainly for the resection of gastric lesions and squamous esophageal neoplasia, and also Western countries have been increasingly implementing ER in the treatment of early gastroesophageal neoplasia, mostly associated with Barrett's esophagus (BE). In BE, however, there is still a risk of metachronous lesions in the remainder of the Barrett's after focal ER. Additional treatment of all Barrett's mucosa is therefore advised. Currently, the most effective method for this is by using radiofrequency ablation (RFA). This review will provide an overview of indications for ER and RFA. Key Messages and Conclusions: Endoscopic management of early esophageal neoplasia is a safe and valid alternative to surgery and is nowadays the treatment of choice. ER is the mainstay of endoscopic management of early esophageal neoplasia since it allows for removal of neoplastic lesions and provides a large tissue specimen for histological evaluation. In case of early neoplasia in BE, focal ER should be complemented by eradication of the remaining Barrett's mucosa. RFA has proven to be a safe and effective modality to achieve complete eradication of Barrett's mucosa.	esophagus
Prognostic factors in clinical T1N0M0 thoracic esophageal squamous cell carcinoma invading the muscularis mucosa or submucosa.	BACKGROUND: Multimodality treatment is widely performed for clinical T1N0M0 (UICC-TNM classification, 7th edition) thoracic esophageal squamous cell carcinoma (ESCC), but available articles regarding treatment results are limited. This study assessed the outcomes of clinical T1N0M0 thoracic ESCC invading the muscularis mucosa (MM) or submucosa (SM) treated with radiotherapy (RT) or chemoradiotherapy (CRT). METHODS: We retrospectively reviewed the medical charts of 90 patients with clinical T1N0M0 thoracic ESCC treated with RT or CRT in our hospital in 2004-2011. Of these 90 patients, we analyzed the cases of 71 patients who met our inclusion criteria. All 71 patients had MM or SM cancer. In the 47 patients treated with CRT, the chemotherapy regimen of 5-fluorouracil (5-FU) plus cisplatin (CDDP) was used for 46 patients and 5-FU and nedaplatin was used for one patient. Forty-five patients underwent endoscopic resection (ER) followed by RT or CRT as an additional treatment. Elective nodal irradiation (ENI) was used in 39 patients. For all analyses, statistical significance was defined as 0.05, and the Bonferroni correction was used for the multivariate analysis. RESULTS: The median age was 70 years (range 47-84). With a median follow-up of 43.6 months (range 1.5-124.2), the 5-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) rates were 64.0, 72.8 and 50.0 %, respectively. The multivariate analysis showed that performance status (PS) was an independent prognostic factors for DSS and DFS (DSS, p < 0.001; DFS, p < 0.001). Chemotherapy in addition to RT showed a trend for better DSS (p = 0.032) but was not significant following Bonferroni correction. ER and ENI were not significant predictive factors for DSS and DFS. CONCLUSIONS: PS was an independent prognostic factor for DSS and DFS. ER and ENI had no significant relationship with DSS or DFS. The present results may be helpful in treatment decisions for clinical T1N0M0 thoracic ESCC.	esophagus
miR-124 radiosensitizes human esophageal cancer cell TE-1 by targeting CDK4.	Radiotherapy is one of the most important treatments for esophageal cancer, but radioresistance remains a major challenge. Previous studies have shown that microRNAs (miRNAs or miRs) are involved in human cancers. miR-124 has been widely reported in various cancers and it is intimately involved in proliferation, cell cycle regulation, apoptosis, migration, and invasion of cancer cells. The aim of this study was to explore the relationship between the miR-124/cyclin-dependent kinase 4 (CDK4) axis and the radiosensitivity of esophageal cancer cells. In this study, we identified the reduced expression of miR-124 in 18 paired esophageal cancer tissues compared to their matched normal tissues. In order to investigate the physiological role of miR-124 in esophageal cancer, the cell counting kit-8 (CCK-8) assay and wound healing assay were performed, and the results suggest that miR-124 overexpression decreases tumor growth and aggression. Next, we detected the effects of ectopic miR-124 expression on the apoptosis of an esophageal cancer cell line (TE-1) following radiotherapy. Using the CCK-8 assay and Hoechst 332528 stain, we found that ectopic expression of miR-124 led to a higher percentage of apoptotic cells. Finally, we identified that CDK4 is a direct target of miR-124 in TE-1 cells using target prediction algorithms and a luciferase reporter assay. Moreover, western blot assay confirmed that CDK4 was downregulated during miR-124 transfection. Taken together, we illustrate that the miR-124/CDK4 axis plays an important role in radiation sensitivity of human esophageal cancer cells by targeting CDK4.	esophagus
"Usage of ""Reversal Penetrating Technique"" with Ancillary Trocar in Minimally Invasive Ivor Lewis Esophagectomy."	"OBJECTIVE: We present a ""Reversal Penetrating Technique"" (RPT) to perform thoracoscopic esophagogastric anastomosis in Ivor Lewis minimally invasive esophagectomy (MIE). The safety and efficiency of this technique are evaluated. PATIENTS AND METHODS: RPT was used in Ivor Lewis MIE for treating patients with distal esophageal cancer. A specific anvil set is inserted into proximal esophagus lumen to allow its prefixed Prolene suture to pierce from the inside out. Then, the suture is pulled until the anvil rod penetrates the esophageal wall. The esophageal stump and anvil placement are completed after the esophagus is transected by a linear stapler. After the circular stapler is docked with the anvil, the intrathoracic anastomosis is performed in a side-to-side manner. RESULTS: Since August 2012, RPT anastomosis was successfully performed in 30 consecutive patients without conversion to other anastomotic techniques or open surgery. No patient experienced anastomotic leak or gastric tube necrosis. No postoperative deaths occurred. No patient complained of remarkable dysphasia during follow-up. Twenty six patients were checked by gastroscopy, no localized recurrence or anastomotic stricture was identified. CONCLUSIONS: RPT is less technically challenging as it eliminates the need for sewing and trimming of esophageal remnant. This technique is safe and efficient, and is particularly suited to those who do not have access to the Orvil device when performing Ivor Lewis MIE."	esophagus
Comprehensive immunohistochemical analysis of tumor microenvironment immune status in esophageal squamous cell carcinoma.	Immunotherapy with anti-PD-1 antibody preliminarily showed promising efficacy for treating esophageal squamous cell carcinoma (ESCC). Herein, we used tissue microarrays and immunohistochemically analyzed PD-L1 and various tumor infiltrating immune cells (TIICs) in specimens from 196 ESCC patients who had undergone curative resection without preoperative therapy. PD-L1 expressions in tumor cells (TCs) and TIICs, as well as infiltration of lymphocytes (CD4+, CD8+, FOXP3+, and PD- 1+) and macrophages (CD68+ and CD204+), were evaluated. PD-L1 was expressed in TCs of 18.4% and in TIICs of 83.3% of these patients. PD-L1 expressions in TCs and TIICs were associated with significant infiltration of various TIIC types, especially CD8+ cells. PD-L1 expressions in both TCs and TIICs were significantly associated with favorable overall survival, and combining their levels enhanced prognostic accuracy. Prognostic impacts of PD-L1 expressions in TCs and TIICs, abundant PD-1+ cell infiltration, a high CD8+/FOXP3+ ratio, and the CD8+/CD204+ ratio remained significant after adjusting for clinicopathological factors. In conclusion, PD-L1 expression reflects anti-tumor immunity, and PD-1/PD-L1 expression and the ratio of infiltrating effector to immune suppressor cells have prognostic value. Therapeutic strategies inhibiting the PD-1/PD-L1 signal and immune suppressor cells are anticipated in ESCC patients.	esophagus
Somatically Acquired LINE-1 Insertions in Normal Esophagus Undergo Clonal Expansion in Esophageal Squamous Cell Carcinoma.	Squamous cell carcinoma of the esophagus (SCC) is the most common form of esophageal cancer in the world and is typically diagnosed at an advanced stage when successful treatment is challenging. Understanding the mutational profile of this cancer may identify new treatment strategies. Because somatic retrotransposition has been shown in tumors of the gastrointestinal system, we focused on LINE-1 (L1) mobilization as a source of genetic instability in this cancer. We hypothesized that retrotransposition is ongoing in SCC patients. The expression of L1 encoded proteins is necessary for retrotransposition to occur; therefore, we evaluated the expression of L1 open reading frame 1 protein (ORF1p). Using immunohistochemistry, we detected ORF1p expression in all four SCC cases evaluated. Using L1-seq, we identified and validated 74 somatic insertions in eight tumors of the nine evaluated. Of these, 12 insertions appeared to be somatic, not genetically inherited, and sub-clonal (i.e., present in less than one copy per genome equivalent) in the adjacent normal esophagus (NE), while clonal in the tumor. Our results indicate that L1 retrotransposition is active in SCC of the esophagus and that insertion events are present in histologically NE that expands clonally in the subsequent tumor.	esophagus
Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma.	BACKGROUND: Despite the recent improvements in multimodal therapies for oesophageal squamous cell carcinoma (ESCC), the prognosis remains poor. The identification of suitable biomarkers for predicting the prognosis and chemo-sensitivity is required to develop targeted treatments and improve treatment results. METHODS: Proteins highly expressed in ESCC cell lines compared with normal oesophageal cell lines were screened by isobaric tag for relative and absolute quantitation (iTRAQ). We identified glypican-1 (GPC1) as a novel molecule. The clinicopathological characteristics of GPC1 were evaluated by immunohistochemistry using ESCC specimens, and clinical parameters were assessed. The correlation between GPC1 expression levels and chemo-sensitivity were analysed in vitro. RESULTS: In the immunohistochemical assessment of 175 ESCC patients, 98.8% expressed GPC1. These patients demonstrated significantly poorer prognosis compared with patients with low-GPC1 expression by survival assay (P<0.001). Higher chemoresistance was observed in the GPC1 high-expression group. GPC1 expression levels positively correlated with chemo-sensitivity against cis-Diammineplatinum (II) dichloride (CDDP), and are potentially associated with anti-apoptotic function based on alterations in the MAPK downstream signalling pathway and Bcl-2 family member proteins. CONCLUSIONS: GPC1 is an independent prognostic factor in ESCC and is a critical molecule for altering the threshold of chemoresistance to CDDP.	esophagus
Safety and Efficacy of a Novel Double-Stapling Technique for Distal Esophageal Resection and Esophago-Jejunal Anastomosis.	BACKGROUND: The purpose of this study was to evaluate safety and efficacy of a new esophagojejunal anastomosis (EJA) technique allowing the insertion of the anvil of a common circular stapler without hand-sewn securing. METHODS: From August 2014 to May 2015, 20 consecutive patients with esophagogastric junction adenocarcinoma underwent surgery. EJA was performed using a new technique; the free margins of the esophageal stump were suspended and the anvil of a circular stapler on a new dedicated and registered support bar (characterized by a push-rod making possible to hook-unhook the anvil of the circular stapler) was inserted into the lumen. Subsequently, the linear suturing stapler was closed over the bar and fired to suture the distal stump of the esophagus; the bar was retracted and the push-rod of the anvil was pulled out through the linear suture. Finally, the anastomosis was performed using a circular stapler. RESULTS: There were no intraoperative complications, and R0 resection was achieved in all cases. Postoperative course has been uneventful for 18 patients (90%). Only 1 patient (5%) developed fistula, conservatively treated. CONCLUSIONS: Our preliminary clinical experience suggested that this technique was safe and efficient (for all online suppl. material, see www.karger.com/doi/10.1159/000446856).	esophagus
Comparison of Endoscopic Resection and Minimally Invasive Esophagectomy in Patients With Early Esophageal Cancer.	OBJECTIVE: To determine whether endoscopic resection (ER) and minimally invasive esophagectomy (MIE) are safe and effective for treating squamous intraepithelial neoplasia of the esophagus. MATERIALS AND METHODS: This study retrospectively analyzed a total of 99 consecutive patients with pathologically confirmed early esophageal cancer between December 2007 and 2011. ER was performed in 59 patients, whereas MIE was performed in 40 patients. We compared the 2 groups according to R0 resection rates, treatment-related complications, mean hospital stay, local recurrence rates, and 3- and 4-year overall survival. RESULTS: No significant differences were found in the R0 resection rates between ER and MIE (94.9% vs. 97.5%, P>0.05). The occurrence rate of minor complications in the ER group was significantly lower than that in the thoracoscopic esophagectomy group (11.8% vs. 32.5%, P>0.05). The mean operative time in the ER group was 74±23 minutes, which was significantly shorter than that in the MIE group (298±46 min). The average length of hospital stay in the ER group was significantly shorter than that in the MIE group (P<0.001). No significant differences were observed in the local recurrence rates between the 2 groups (P>0.05). Similarly, no differences were found in the 3-year survival rate (ER: 96.6%, vs. MIE: 97.5%, P>0.05) and 4-year survival rate (ER: 91.5% vs. MIE: 90%, P>0.05) between the 2 groups. CONCLUSIONS: ER achieves the same positive results as MIE in the treatment of early esophageal cancer and is associated with a lower complication rate, a shorter recovery time, and a similar survival rate. However, multiple ER procedures were required for several patients in this study.	esophagus
Racial Disparity in the Sex Distribution, the Prevalence, and the Incidence of Dysplasia in Barrett's Esophagus.	GOALS: Our aim was to study the prevalence of dysplasia and progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in African Americans (AA) with Barrett's esophagus (BE) and compare it with that of non-Hispanic white (NHW) controls. BACKGROUND: BE, a precursor of EAC, is a disease of predominantly white men and is uncommon in AA. The prevalence of dysplasia and progression to HGD and EAC in AA patients with BE is not clearly known. STUDY: All AA or NHW patients with confirmed BE, that is specialized intestinal metaplasia, seen between 2002 and 2013 at our institution were included. Variables such as age, gender, medication use, the body mass index, the date of endoscopy, the hiatal hernia size, the BE length, and histologic findings were noted. Progression to HGD/EAC was evaluated. RESULTS: Fifty-two AA and 2394 NHW patients with BE were identified. There was a higher percentage of women in the AA cohort (46.2%) than in the NHW cohort (24.9%, P<0.001). Nondysplastic BE was more prevalent in AA than in NHW (80.8% vs. 68.4%, P=0.058). In the surveillance cohort of 20 AA and 991 NHW, no racial differences in progression to HGD/EAC were observed during a median follow-up of 43 months. CONCLUSIONS: This study includes the largest number of AA with histologically confirmed BE reported so far. About 46.2% of the AA cohort with BE in our study consisted of women. There was a trend toward a higher prevalence of nondysplastic BE in AA compared with NHW.	esophagus
Risk Factors for Local Recurrence and Optimal Length of Esophagectomy in Esophageal Squamous Cell Carcinoma.	BACKGROUND: The risk factors for local recurrence in residual esophagus after esophagectomy have not been well documented. This study aimed to identify risk factors of local recurrence and optimal length of esophageal resection in esophageal cancer. METHODS: Patients who underwent curative esophagectomy with more than 2 years of follow-up were included. Patients who received preoperative chemoradiation or in whom the ex vivo length of proximal margin (LPM) from resected tumor was not documented in the pathologic report were excluded. A total of 551 patients from January 1995 to February 2013 were included. RESULTS: Complete resection was possible in 516 patients (94%), and mean LPM was 3.4 ± 2.5 cm. Sex, age, location of tumor, location of anastomosis, minimally invasive esophagectomy, three-field lymphadenectomy, cell type, differentiation, proximal resection margin status, tumor size, number of dissected lymph nodes, and T stages were not risk factors for local recurrence in multivariate analysis. The N stage (p = 0.034) and LPM (p = 0.007) were risk factors for local recurrence in multivariate analysis. The LPM was not related to local recurrence in N0, but 5-year freedom from local recurrence was higher for LPM of 5 cm or greater in N+ esophageal cancer (72% in LPM less than 5 cm versus 93% in LPM of 5 cm or greater, p = 0.040). CONCLUSIONS: Local recurrence after esophagectomy in esophageal cancer is related to lymphatic metastasis rather than to proximal margin status, which raises the possibility that the main mechanism of local recurrence is submucosal lymphatic metastasis. Esophagectomy with LPM more than 5 cm is recommended for esophageal cancer with nodal metastasis.	esophagus