crossing96/oncoscreening huggingface dataset:
Phosphorylation of ETS-1 is a critical event in DNA polymerase iota-induced invasion and metastasis of esophageal squamous cell carcinoma.	An aberrantly elevated expression of DNA polymerase ι (Pol ι) is significantly associated with poor prognosis of patients with esophageal squamous cell carcinoma (ESCC), yet the mechanisms behind this phenomenon remain obscure. Based on the RNA-Seq transcriptome and real-time PCR analysis, we identified ETS-1 as a candidate gene involved in Pol ι-mediated progression of ESCC. Wound-healing and transwell assay indicated that downregulation of ETS-1 attenuates Pol ι-mediated invasiveness of ESCC. Signaling pathway analysis showed that Pol ι enhances ETS-1 phosphorylation at threonine-38 through the Erk signaling pathway in ESCC cells. Kaplan-Meier analysis, based on 93 clinical tissue samples, revealed that ETS-1 phosphorylation at threonine-38 is associated with poor prognosis of ESCC patients. The present study thus demonstrates that phosphorylation of ETS-1 is a critical event in the Pol ι-induced invasion and metastasis of ESCC.	esophagus
Local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.	BACKGROUND: Radiotherapy is an effective treatment for the postoperative loco-regional recurrence of esophageal cancer; however, the optimal treatment field remains controversial. This study aims to evaluate the outcome of local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer. METHODS: We retrospectively investigated 35 patients treated for a postoperative loco-regional recurrence of esophageal cancer with local field radiotherapy between December 2008 and March 2016. The median irradiation dose was 60 Gy (range: 50-67.5 Gy). Thirty-one (88.6%) patients received concurrent chemotherapy. RESULTS: The median follow-up period was 18 months (range: 5-94 months). The 2-year overall survival was 55.7%, with a median survival time of 29.9 months. In the univariate analysis, the maximal diameter ≤20 mm (P = 0.0383), solitary lesion (P = 0.0352), and the complete remission after treatment (P = 0.00411) had a significantly better prognosis. A total of 27 of 35 patients (77.1%) had progressive disease (loco-regional failure [n = 9], distant metastasis [n = 7], and both loco-regional failure and distant metastasis [n = 11]). No patients had Grade 3 or greater mucositis. CONCLUSION: Local field radiotherapy is a considerable treatment option for postoperative loco-regional recurrence of esophageal cancer.	esophagus
Nano Let‑7b sensitization of eliminating esophageal cancer stem‑like cells is dependent on blockade of Wnt activation of symmetric division.	The poor therapy response and poor prognosis of esophageal cancer has made it one of the most malignant carcinoma, and the complicated multidisciplinary treatment failed to achieve a long-term disease-free survival. To diagnose esophageal cancer at an earlier stage, and to improve the effect of anticancer therapy would improve the therapeutic efficacy. After retrospective analysis of the cancer samples of patients who received esophagectomy, we found the relevance between ratio of either ALDH1 or CD133-positive cancer stem cells and 2-year recurrence. Higher ratios of cancer stem cells indicated later clinical stages, and Wnt signaling activation was more frequent in later esophageal carcinoma. Further in bench studies, we explored the suppressive roles and the mechanisms involved in Let‑7 on self-renewal in ECA‑109 and ECA‑9706 esophageal cancer stem cells. Isolated cancer stem cells naturally divide symmetrically and are therapy resistant. Therapy of fluorouracil and docetaxel both enriched the stem cells, proving the resistant characteristics of cancer stem cells. Wnt activation stimulated more symmetric division of stem cells, resulting in self-renewal promotion, which could be blocked by Let‑7 overexpression. Furthermore, enforced Let‑7 sensitized the stem cells to chemotherapies in a Wnt pathway inhibition-dependent manner, contributing to Let‑7 sensitization of chemotherapeutic response. Wnt activation weakened the suppressive Let‑7b through the sponge functions of CCAT-1, forming the negative feedback loop of Let‑7b/Wnt/CCAT1. These results identified the crucial participation of stem cells in esophageal cancer occurrence and progression as the potent indicator, and also indicate the potential powerful agent of Let‑7 nano-particles in treatment of cancer.	esophagus
Swainsonine Inhibits Invasion and the EMT Process in Esophageal Carcinoma Cells by Targeting Twist1.	Esophageal cancer is a common gastrointestinal cancer, with a very high mortality rate in patients with metastasis. Swainsonine, a cytotoxic fungal alkaloid, has been shown to inhibit cell growth in esophageal cancer. In the present study, we explored the effects of swainsonine on cell invasion and metastasis in esophageal cancer cells. Human esophageal carcinoma cells were treated with different doses of swainsonine, and then cell viability, invasion, and apoptosis were measured. The mRNA and protein expressions of Twist1, apoptosis- and EMT-related factors, and PI3K/AKT pathway factors were detected by qRT-PCR and Western blot. Swainsonine had no effect on esophageal cancer cell viability and apoptosis, but it significantly decreased cell invasion in a dose-dependent manner. Swainsonine increased the expression of E-cadherin but decreased the expression of N-cadherin, vimentin, ZEB1, and snail in a dose-dependent manner, thereby inhibiting EMT. Last, we found that swainsonine inhibits cell invasion and EMT in the esophageal carcinoma cells by downregulation of Twist1 and deactivation of the PI3K/AKT signaling pathway.	esophagus
[Surgical Treatment for Synchronous Double Cancer of the Thoracic Esophagus and Lung].	We herein report 2 cases of radical operation for synchronous double cancer of the thoracic esophagus and each side of the lung. Case 1:A 71-year-old woman with synchronous double cancer of the thoracic esophagus (Mt, T3N2M0, Stage III) and right lung (M, T2aN0M0, Stage I B) underwent esophagectomy concomitantly with right middle lobectomy through right thoracotomy (single-stage operation) after 2 courses of systemic chemotherapy with docetaxel, cisplatin and 5-fluorouracil( DCF regimen). Case 2:A 72-year-old man with synchronous double cancer of the thoracic esophagus( MtLt, T3N2M0, Stage III) and left lung( U, T1aN0M0, Stage I A) underwent 2-stage operation after 2 courses of the DCF therapy. Esophagectomy through right thoracotomy was performed followed by left upper lobectomy through left thoracotomy 3 months later. Treatment strategy for synchronous double cancer of the thoracic esophagus and lung is discussed based on our experiences and previous reports.	esophagus
Effects of preemptive analgesia with flurbiprofen ester on lymphocytes and natural killer cells in patients undergoing esophagectomy: A randomized controlled pilot study.	BACKGROUND: Tumors may induce systemic immune dysfunction, which can be aggravated by surgery and anesthesia/analgesia. Data on the effect of flurbiprofen preemptive analgesia on immune dysfunction is limited. The aim of this study was to investigate the effect of flurbiprofen preemptive analgesia on lymphocytes and natural killer (NK) cells in patients undergoing thoracotomy and thoracoscopy radical esophagectomy, and to explore the analgesic methods suitable for tumor patients. METHODS: This was a randomized controlled pilot study of 89 patients with esophageal cancer treated with surgery at the Henan Cancer Hospital between January 1, 2015 and December 31, 2016. The patients were divided into three groups: group 1, thoracotomy; group 2, thoracoscopy and laparoscopic surgery; and group 3, flurbiprofen, thoracoscopy, and laparoscopic surgery. CD3+, CD19+, NK, CD4+, and CD8+ cells in whole blood were measured by flow cytometry 30 minutes before surgery (T0), at the end of the thoracic section of the procedure (T1), and at the end of the operation (T2). RESULTS: There were no significant differences in CD3+, CD19+, CD8+, NK, and CD4+ cells between the three groups or regarding the time points during the procedure (all P > 0.05). Thoracotomy and thoracoscopy surgery resulted in similar immunological outcomes. CONCLUSION: Flurbiprofen ester preemptive analgesia did not suppress the immune function in patients and could be a safe analgesic method for patients with esophageal cancer undergoing surgery.	esophagus
Molecular Mechanisms of Acetaldehyde-Mediated Carcinogenesis in Squamous Epithelium.	"Acetaldehyde is a highly reactive compound that causes various forms of damage to DNA, including DNA adducts, single- and/or double-strand breaks (DSBs), point mutations, sister chromatid exchanges (SCEs), and DNA-DNA cross-links. Among these, DNA adducts such as N²-ethylidene-2'-deoxyguanosine, N²-ethyl-2'-deoxyguanosine, N²-propano-2'-deoxyguanosine, and N²-etheno-2'-deoxyguanosine are central to acetaldehyde-mediated DNA damage because they are associated with the induction of DNA mutations, DNA-DNA cross-links, DSBs, and SCEs. Acetaldehyde is produced endogenously by alcohol metabolism and is catalyzed by aldehyde dehydrogenase 2 (ALDH2). Alcohol consumption increases blood and salivary acetaldehyde levels, especially in individuals with ALDH2 polymorphisms, which are highly associated with the risk of squamous cell carcinomas in the upper aerodigestive tract. Based on extensive epidemiological evidence, the International Agency for Research on Cancer defined acetaldehyde associated with the consumption of alcoholic beverages as a ""group 1 carcinogen"" (definite carcinogen) for the esophagus and/or head and neck. In this article, we review recent advances from studies of acetaldehyde-mediated carcinogenesis in the squamous epithelium, focusing especially on acetaldehyde-mediated DNA adducts. We also give attention to research on acetaldehyde-mediated DNA repair pathways such as the Fanconi anemia pathway and refer to our studies on the prevention of acetaldehyde-mediated DNA damage."	esophagus
Pathological complete response in patients with esophageal cancer after the trimodality approach: The association with baseline variables and survival-The University of Texas MD Anderson Cancer Center experience.	BACKGROUND: Reports are limited regarding clinical and pretreatment features that might predict a pathological complete response (pathCR) after treatment in patients with esophageal cancer (EC). This might allow patient selection for different strategies. This study examines the association of a pathCR with pretreatment variables, overall survival (OS), recurrence-free survival (RFS), and patterns of recurrence in a large cohort from a single institution. METHODS: The baseline clinical features of 911 consecutive patients with EC who were treated with trimodality therapy from January 2000 to November 2013 were analyzed. A pathCR was defined as a surgical specimen with no residual carcinoma (primary or nodes). Logistic regressions were used to identify independent baseline features associated with a pathCR. We applied log-rank testing and Cox models to determine the association between a pathCR and the time-to-event outcomes (OS and RFS). RESULTS: Of 911 patients, 218 (23.9%) achieved a pathCR. The pathCR rate was 23.1% for adenocarcinoma and 32.2% for squamous cell carcinoma. A lower pathCR rate was observed for 1) older patients (>60 years), 2) patients with poorly differentiated tumors, 3) patients with signet ring cells (SRCs), and 4) patients with a higher T stage. Patients with a pathCR had longer OS and RFS than those without a pathCR (P = .0021 and P = .0011, respectively). Recurrences occurred more in non-pathCR patients. Distant metastases were the most common type of recurrence. PathCR patients developed brain metastases at a marginally higher rate than non-pathCR patients (P = .051). CONCLUSIONS: In this large cohort study, a pathCR is confirmed to be associated with better OS and RFS. The presence of a poorly differentiated tumor or SRCs reduces the likelihood of a pathCR. Future research should focus on molecular classifiers. Cancer 2017;123:4106-4113. © 2017 American Cancer Society.	esophagus
Outcomes of nutritional interventions to treat dysphagia in esophageal cancer: a population-based study.	Esophageal cancer (EC) is increasing in prevalence due to rising incidence and improved treatment strategies. Dysphagia is a significant morbidity in patients with EC requiring nutritional intervention. We sought to evaluate outcomes of nutritional interventions for EC patients hospitalized with dysphagia at a population level. The National Inpatient Sample (2002-2012) was utilized to include all adult inpatients (≥18 years of age) with EC and presence of dysphagia and stricture that underwent nutritional interventions including feeding tube (FT) placement, esophageal stenting, or parenteral nutrition (PN). Temporal trends were examined with multivariate analysis performed for mortality, length of stay (LOS), and cost of hospitalization. A total of 509,593 EC patients had 12,205 hospitalizations related to dysphagia. The hospitalization rates doubled over the study period (1.52% vs. 3.28%, p < 0.001). The most common nutritional intervention was FT (27%), followed by esophageal stenting (13%), and PN (11%). PN was more frequently associated with a diagnosis of sepsis (6.1%, p = 0.023) compared to FT (2.5%) or esophageal stenting (1.8%). Multivariate analysis demonstrated FT and esophageal stenting had comparable mortality (OR 1.06, 95% CI: 0.49, 2.32); however, PN was associated with higher mortality (OR 2.37, 95% CI: 1.22, 4.63), cost of hospitalization ($5,510, 95% CI: 2,262, 8,759), and LOS (2.13 days, 95% CI: 0.72, 3.54). This study shows that hospitalizations for EC with dysphagia and related nutritional interventions are increasing. As a single modality, parenteral nutrition should be avoided. Among our esophageal stent and FT population, further studies are necessary to determine adequate interventions based on disease stage.	esophagus
Does physical activity protect against the development of gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma? A review of the literature with a meta-analysis.	Physical activity affects the functioning of the gastrointestinal system through both local and systemic effects and may play an important role in reducing the risk of esophageal adenocarcinoma. This review assesses the biological mechanisms and epidemiological evidence for the relationship between physical activity and the development of esophageal adenocarcinoma and its precursor diseases: gastroesophageal reflux disease (GORD) and Barrett's esophagus. A search of PubMed, Medline, Embase, and CINAHL was conducted from their inceptions to 25th March 2017 for analytical studies that examined associations between recreational and/or occupational levels of physical activity and the risk of GORD, Barrett's esophagus, and esophageal adenocarcinoma. Where appropriate, a meta-analysis of effects was undertaken. Seven studies were included (2 cohort, 5 case control). For GORD, there were three case-control studies with 10 200 cases among 78 034 participants, with a pooled estimated OR of 0.67 (95% CI 0.57-0.78) for high versus low levels of recreational physical activity. In Barrett's esophagus, there was a single case-control study, which reported no association, OR 1.19 (95% CI 0.82-1.73). For esophageal adenocarcinoma, there were three studies (two prospective cohort, one case control) with 666 cases among 910 376 participants. The largest cohort study reported an inverse association for high versus low levels of recreational physical activity, RR 0.68, 95% CI 0.48-0.96. The remaining two studies reported no associations with either occupational or combined recreational and occupational activity. Heterogeneity in the measurement of exposure (recreational, occupational, and both) made a pooled estimate for esophageal adenocarcinoma inappropriate. Although limited, there is some evidence that higher levels of recreational physical activity may reduce the risk of both GORD and esophageal adenocarcinoma, but further large cohort studies examining the type, intensity and duration of activities that may be beneficial are needed.	esophagus
Changes in esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer: a high-resolution manometry study.	The effect of endoscopic submucosal dissection (ESD) on esophageal motility remains unknown. Therefore, the aim of this study is to elucidate changes in esophageal motility after ESD along with the cause of dysphagia using high-resolution manometry (HRM). This is a before-and-after trial of the effect of ESD on the esophageal motility. Twenty patients who underwent ESD for superficial esophageal carcinoma were enrolled in this study. Patients filled out a questionnaire about dysphagia and underwent HRM before and after ESD. Results before and after ESD were compared. Data were obtained from 19 patients. The number of patients who complained of dysphagia before and after ESD was 1/19 (5.3%) and 6/19 (31.6%), respectively (P = 0.131). Scores from the five-point Likert scale before and after ESD were 0.1 ± 0.5 and 1.0 ± 1.6, respectively (P = 0.043). The distal contractile integral (DCI) before and after ESD and the number of failed, weak, or fragmented contractions were not significantly different. However, in five patients with circumferential ESD, DCI was remarkably decreased and the frequency of fail, weak, or fragmented contractions increased. Univariate regression analysis showed a relatively strong inverse correlation of ΔDCI with the circumferential mucosal defect ratio {P < 0.01, standardized regression coefficient (r) = -0.65}, the number of stricture preventions (P < 0.01, r = -0.601), and the number of stricture resolutions (P < 0.01, r = -0.77). This HRM study showed that impairment of esophageal motility could be caused by ESD. The impairment of esophageal motility was conspicuous, especially in patients with circumferential ESD and subsequent procedures such as endoscopic triamcinolone injection and endoscopic balloon dilatation. Impaired esophageal motility after ESD might explain dysphagia.	esophagus
Balloon-based esophageal cryoablation with a novel focal ablation device: dose-finding and safety in porcine and human models.	The new Cryoballoon Focal Ablation System (CbFAS), a through-the-scope catheter with battery-powered handle that delivers cryogenic fluid into an inflated balloon, differs from current cryotherapy methods used for treatment of Barrett's epithelium. In this dose-finding study, short- and long-term histopathological effects and safety of the CbFAS were evaluated. Cryoablations with (supra)therapeutic durations (4-24 seconds) were performed in pigs that survived for 12 or 48 hours or 4 or 28 days. Next, cryoablations (durations based on animal data) were performed in normal mucosa of esophageal cancer patients scheduled to undergo esophagectomy. The outcome parameters, the occurrence of any bleeding or perforation, the histological presence of edema, inflammation, and necrosis throughout the esophageal wall layers, were evaluated. A total of 60 cryoablations were performed in 11 pigs. 48 hour cryoablations with therapeutic durations (4-10 seconds) resulted in edema/inflammation as deep as the serosa and necrosis ranging from submucosa to serosa with a median depth of 3.2 mm. In 4 day cryoablations this was in the serosa, and muscularis tunica to serosa at a median depth of 4.5 mm, respectively. No necrosis or inflammation remained after 28 days, not even after supratherapeutic cryoablation (12-24 seconds). No acute or delayed bleeding or perforation was observed. Next, eight 6-second cryoablations were performed in four patients. Direct postablation mucosal necrosis was observed; after 4 days necrosis and inflammation was limited to the submucosa. CbFAS cryoablation penetrates deeply into the esophageal wall layers resulting in severe early ablation. After 4 weeks, little injury and no fibrosis remain, even after supratherapeutic durations of administration, suggesting that CbFAS combines deep ablation with a potentially favorable safety profile.	esophagus
Influence of esophagectomy on the gastroesophageal reflux in patients with esophageal cancer.	This study aims to assess the influence of esophagectomy with gastric transposition on the gastroesophageal reflux (GER) and gastric acidity in patients with esophageal cancer. Data on 53 esophageal cancer patients who underwent 24-hour impedance-pH monitoring after esophagectomy were retrospectively analyzed. We used a solid-state esophageal pH probe in which the esophageal pH sensor is placed 1.5 cm distal to the upper esophageal sphincter and the gastric pH sensor is located 15 cm distal to the esophageal pH channel. 24-hour impedance-pH monitoring data and other clinical data including anastomosis site stricture and incidence of pneumonia were collected. We defined pathologic reflux with reference to known normative data. Stricture was defined when an intervention such as bougienage or balloon dilatation was required to relieve dysphagia. The esophageal and gastric mean pH were 5.47 ± 1.51 and 3.33 ± 1.64, respectively. The percent time of acidic pH (<4) was 6.66 ± 12.49% in the esophagus and 70.53 ± 32.19% in the stomach. Esophageal pathologic acid reflux was noticed in 32.1%, 20.8%, and 35.8% during total, upright, and recumbent time, respectively. Esophageal pathologic bolus reflux was noted in 83.0%, 77.4%, and 64.2% during total, upright, and recumbent time, respectively. Gastric acidity increased with time after esophagectomy. Esophageal acid exposure time correlated with intragastric pH. However, esophageal pathologic acid reflux was not associated with anastomosis site stricture or pneumonia. In conclusion, GER frequently occurs after esophagectomy. Thus, strict lifestyle modifications and acid suppression would be necessary in patients following esophagectomy.	esophagus
Induction therapy before surgery improves survival in patients with clinical T3N0 esophageal cancer: a nationwide study in Taiwan.	The utility of induction therapy (IT) in patients with resectable esophageal cancer remains controversial, especially when clinical evidence of nodal metastases is lacking. We sought to compare the survival impact of IT versus upfront surgery (US) in patients with cT3N0 esophageal cancer. We searched the Taiwan Cancer Registry for patients with cT3N0 esophageal cancer who underwent US or IT between 2008 and 2013. Multivariate Cox regression analysis was used to analyze the potential benefits of IT in terms of overall survival (OS) and disease-free survival (DFS). Of the 11752 patients with esophageal cancer included in the nationwide database, 762 (6.5%) had cT3N0 disease. Most cases (720 [94.5%]) had a histological diagnosis of squamous cell carcinoma. Of them, 135 received IT (the IT group) and 237 received surgery first (the US group). In the US group, pretreatment clinical staging was accurate in 47.9% of patients. Twenty-one (8.97%) were clinically overstaged (pT1-2N0), whereas 101 (43.17%) were clinically understaged (pT4N0 or pTanyN1-3). The presence of unexpected nodal metastases was identified in 92.1% of clinically understaged patients. In the IT group, 28 (20.74%) patients did not proceed to surgery after IT. The use of IT was associated with higher R0 resection rates and fewer pathological nodal metastases, despite unexpected M1 disease being more common (all P< 0.05). The 5-year OS rate was significantly higher (42%) in the IT group than in the US group (33%, P= 0.032). Similar findings were observed in terms of 5-year DFS (37% in the IT group versus 29% in the US group, P= 0.009). Multivariate analysis identified US (hazard ratio: 1.42, P= 0.03) and non-R0 resection (hazard ratio: 1.58, P= 0.03) as independent adverse prognostic factors. We found that 43.17% of patients with cT3N0 disease undergoing primary surgery had their disease understaged. The use of IT before esophagectomy significantly improves OS and DFS in patients with clinical T3N0 esophageal squamous cell carcinoma.	esophagus