crossing96/oncoscreening huggingface dataset:
Rate of Recurrent Luminal Esophageal Cancer in Asymptomatic Patients After Curative Treatment for Esophageal Cancer.	GOALS: The goal of this study was to determine the luminal recurrence rate of asymptomatic patients undergoing annual surveillance esophagogastroduodenoscopy (EGD). BACKGROUND: Current guidelines recommend surveillance EGD in postesophagectomy patients with esophageal cancer if there is clinical suspicion of local recurrence. However, many patients undergo annual surveillance EGD despite the recommendations to the contrary. STUDY: A query was performed of all patients who underwent esophagectomy between January 2000 and April 2010 at Moffitt Cancer Center. Patients were included if: they underwent esophagectomy with curative intent, had at least 12 months of follow-up after surgery, and had a R0 resection. Clinical and pathologic data in patients with and without recurrent disease were compared using the Fisher exact tests. Mean differences were examined using the Wilcoxon rank sum test. RESULTS: 346 patients were included with a mean age of 63.5±10.4 years and mean follow-up of 40.9±24.8 months. Recurrence was detected in 89 (25.7%) patients at a mean follow-up of 17.9±15.9 months after surgery. Seventeen (19.1%) patients had recurrence involving the esophagus but 7 (7.9%) patients had associated regional or distant metastases. Nine patients had abnormal signs/symptoms prompting evaluation with EGD. One patient had isolated luminal recurrence. CONCLUSIONS: In this study the majority of patients recurred in the metastatic setting. One (0.29%) patient had localized recurrence; however, it was unclear if this patient had any symptoms or signs to prompt evaluation. Our results support the current recommendation of a symptom-base endoscopic evaluation for esophageal cancer recurrence.	esophagus
Granular cell tumor of the esophagus: a clinicopathological study of 31 cases.	Granular cell tumors (GCTs) in esophagus are rare tumors lacking of systemic large group reports. In this study, we summarized the clinical characteristics, histological features and therapeutic approaches of 31 cases. GCTs generally located at middle and distal of the esophagus in middle aged and elderly patients with no incidence of gender differences. Histologically, tumor cells were mainly plump and polygonal with abundant, granular, amphophilic or eosinophilic cytoplasm. The growth pattern was solid or nested, usually with minimal infiltration and inflammatory infiltrates and lymphoid aggregation. All GCTs in the present study were benign according to Nasser criteria. Nestin, NSE, CD68 and S100 protein were moderate to strong positive. Moreover, a developmental morphology of a GCT was found, which included areas of relatively normal Schwann cells, transitional cells and typical cells of GCTs. All patients received endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Twenty-six patients were followed up and remained clinically well. In conclusion, GCTs of esophagus are neurogenic origin tumors with favourable prognosis. Definite diagnosis of GCTs relies upon pathological examination. The Nasser criteria for stratification are practical in guiding treatment strategy. ESD is a recommended therapeutic strategy, and the range of application is expanding.	esophagus
RNAi screening identifies HAT1 as a potential drug target in esophageal squamous cell carcinoma.	Esophageal carcinoma (EC) is one of the most fatal carcinomas of the gastrointestinal tract. Aberrant activity of histone acetyltransferases (HATs)/deacetylases (HDACs) play a critical role in carcinogenesis through the regulation of the genes involved in cell differentiation, proliferation, and apoptosis. However, cellular functions of HATs/HDACs in esophageal cancer and its molecular mechanisms remain unclear. An RNAi screen was used in this study to identify the histone acetyltransferases (HATs) and deacetylases (HDACs) that could be critical for the survival of EC cells. We demonstrated that HAT1 (histone acetyltransferase 1) was an important determinant to regulate the proliferation of human EC Eca-109 cells. Furthermore, we showed that the knockdown of HAT1 induced a G2/M cell cycle arrest, which was associated with the disruption of cell cycle-related events, including the decrease of cyclinD1 as well as alteration in cyclinB1 expression. The expression of HAT1 was validated to be higher in the primary tumors and adjacent tissue as compared to that of the normal esophageal tissue. Furthermore, we found that HAT1 expression was directly correlated with the poor tumor differentiation of EC tissue, which suggested that HAT1 played an important role in esophageal carcinoma and that it could be a novel EC therapeutic target.	esophagus
Risk factors for weight loss among patients surviving 5 years after esophageal cancer surgery.	BACKGROUND: This study aimed to identify factors influencing postoperative weight loss ≥15 % in long-term survivors after esophageal cancer surgery. METHODS: A population-based study was conducted in Sweden between 2001 and 2005, with regular follow-up for 5 years. Current weight, weight at operation, and average weight were assessed and dichotomized as weight loss of ≥15 %. Logistic regression estimated relative risks of weight loss between pre- and 5 years postoperatively, expressed as odds ratios (ORs) with 95 % confidence intervals (CIs). Statistically significant differences in nutritional symptoms between weight loss groups were analyzed using linear regression models to likewise test as risk factors. Body mass index (BMI) at operation (< or ≥25), sex, and preoperative weight loss (< or ≥10 %) were tested as risk factors. Nutritional symptoms were selected from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-OES18, including fatigue, nausea and vomiting, dyspnoea, appetite loss, diarrhea, and dysphagia, eating difficulties, reflux and pain. RESULTS: A total of 117 patients were included. Patients with preoperative BMI ≥25 were at a threefold increased risk (OR 3.2; 95 % CI 1.4-7.3) for postoperative weight loss of ≥15 % 5 years after operation. Moreover, eating difficulties, pain, fatigue, nausea and vomiting, and appetite loss were clinically relevant and statistically significantly worse symptoms experienced among those with a weight loss of ≥15 % (all at p < 0.05). CONCLUSIONS: Overweight at the time of operation is associated with postoperative weight loss from a long-term perspective. Several nutritional symptoms are associated with weight loss of >15 % 5 years postoperatively.	esophagus
Desmocollin‑2 affects the adhesive strength and cytoskeletal arrangement in esophageal squamous cell carcinoma cells.	Desmocollin‑2 (DSC2), a transmembrane glycoprotein belonging to the desmosomal cadherin family, has been found to be differentially expressed in several types of cancer and to be involved in tumor progression. The tumor metastasis suppressing property of DSC2 in esophageal squamous cell carcinoma (ESCC) has been described, however, its contribution to cell cohesion in ESCC remains to be elucidated. In the present study, using RNA interference (RNAi), the expression of DSC2 was silenced in SHEEC and KYSE510 cells. Hanging drop and fragmentation assays were performed to investigate the role of DSC2 in cell‑cell adhesion. Western blot analysis and confocal microscopy were used to analyze the expression and localization of cell adhesion molecules and cytoskeletal arrangement. The results demonstrated that DSC2 knock down by RNAi caused defects in cell‑cell adhesion and a concomitant reduction in desmosomal protein expression and adherens junction molecule distribution. A decrease in the expression of DSC2 caused an increase in free γ‑catenin levels, thus promoting its recruitment to the adherens junction complex. In addition, the RNAi‑mediated inhibition of DSC2 led to keratin intermediate filament retraction and filamentous‑actin cytoskeleton rearrangement. Taken together, these data support our previous findings and the proposal that DSC2 may be involved in the regulation of the invasive behavior of cells by a mechanism that controls cell‑cell attachment and cytoskeleton rearrangement.	esophagus
KPNA2 is a promising biomarker candidate for esophageal squamous cell carcinoma and correlates with cell proliferation.	Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignant cancers worldwide, with a poor 5-year prognosis. Karyopherin α 2 (KPNA2) is a nuclear membrane protein that mediates nucleus-to-cytoplasm shuttling. Its expression is elevated in multiple forms of cancer, and it can be secreted into the serum. However, the concentration of KPNA2 in serum from ESCC patients and the role of KPNA2 in ESCC cells remains unclear. The aim of the present study was to determine the concentration of KPNA2 in serum from ESCC patients and to investigate the effect of KPNA2 silencing on ESCC cell proliferation. KPNA2 protein expression was detected at the tissue level by immunohistochemistry, in cell lines by western blotting and at the serum level by enzyme linked immunosorbent assay (ELISA). Cell proliferation was determined by cell growth curve and colony formation assay. Stages of the cell cycle were analyzed by flow cytometry. The effect of KPNA2 knockdown on E2F1 translocation was determined by subcellular fractionation. KPNA2 was overexpressed in both ESCC tissues and cell lines compared with controls. The concentration of KPNA2 in serum from ESCC patients was significantly higher than that from healthy controls. The AUC was determined to be 0.804. The sensitivity and specificity of the assay were 76.7 and 75.0%, respectively. To determine the significance of KPNA2 function, small interfering RNA (siRNA) against KPNA2 was used to knock down KPNA2 levels in the ESCC using siRNA in the Kyse510 cell line. KPNA2 siRNA inhibited Kyse510 cell proliferation and colony formation ability and induced a G2/M phase arrest. The nuclear translocation of E2F1 was also reduced in siRNA-treated Kyse510 cells. The KPNA2 protein levels were high in ESCC tumors, and siRNA against KPNA2 could inhibit the growth of ESCC cells, suggesting it may be a new potent marker and therapeutic target for ESCC.	esophagus
Functional analysis of the mRNA profile of neutrophil gelatinase‑associated lipocalin overexpression in esophageal squamous cell carcinoma using multiple bioinformatic tools.	Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin superfamily; dysregulated expression of NGAL has been observed in several benign and malignant diseases. In the present study, differentially expressed genes, in comparison with those of control cells, in the mRNA expression profile of EC109 esophageal squamous cell carcinoma (ESCC) cells following NGAL overexpression were analyzed by multiple bioinformatic tools for a comprehensive understanding. A total of 29 gene ontology (GO) terms associated with immune function, chromatin structure and gene transcription were identified among the differentially expressed genes (DEGs) in NGAL overexpressing cells. In addition to the detected GO categories, the results from the functional annotation chart revealed that the differentially expressed genes were also associated with 101 functional annotation category terms. A total of 59 subpathways associated locally with the differentially expressed genes were identified by subpathway analysis, a markedly greater total that detected by traditional pathway enrichment analysis only. Promoter analysis indicated that the potential transcription factors Snail, deltaEF1, Mycn, Arnt, MNB1A, PBF, E74A, Ubx, SPI1 and GATA2 were unique to the downregulated DEG promoters, while bZIP910, ZNF42 and SOX9 were unique for the upregulated DEG promoters. In conclusion, the understanding of the role of NGAL overexpression in ESCC has been improved through the present bioinformatic analysis.	esophagus
Diagnostic application of PIK3CA mutation analysis in Chinese esophageal cancer patients.	BACKGROUND: The PIK3CA gene mutation was found to associate with prognosis and might affect molecular targeted therapy in esophageal carcinoma (EC). The aim of this study is to compare different methods for analyzing the PIK3CA gene mutation in EC. METHODS: Genomic DNA was extracted from 106 surgically resected EC patient tissues. The PIK3CA mutation status (exons 9 and 20) were screened by mutant-enrich liquid chip (ME-Liquidchip), Sanger sequencing, and pyrosequencing. And all samples with mutations were independently reassessed using amplification refractory mutation system (ARMS) methods again. RESULTS: PIK3CA mutation rates were identified as 11.3% (12/106) by ME-Liquidchip. 10 mutations occurred in exon 9 and 2 in exon 20, including G1624A:E542K (n = 4), G1633A:E545K (n = 6) and A3140G:H1047R (n = 2). The results were further verified by ARMS methods. Among these 12 cases characterized for PIK3CA mutation, however, only 7 and 6 cases were identified by Sanger sequencing (6.6%,7/106) and pyrosequencing (5.7%,6/106), respectively. CONCLUSION: Sanger sequencing and pyrosequencing are less sensitive and are not efficiently applicable to the detection of PIK3CA mutation in EC samples. Choosing between ME-Liquidchip and ARMS will depend on laboratory facilities and expertise. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_153.	esophagus
One decade of experience with endoscopic stenting for intrathoracic anastomotic leakage after esophagectomy: brilliant breakthrough or flash in the pan?	Management of intrathoracic anastomotic leakage after esophagectomy by means of endoscopic stent insertion has gained wide acceptance as an alternative to surgical reintervention. Between January 2004 and March 2013 all patients who underwent esophagectomy at a German high-volume center for esophageal surgery were included in this retrospective study. The study comprises 356 patients. Anastomotic leakage occurred in 49 cases. There were no significant differences in age, American Society of Anesthesiologists (ASA) score, or frequency of neoadjuvant therapy between cases with and without leak. However, leak patients sustained significantly more often postoperative pneumonia, pleural empyema, sepsis, and acute renal failure. Moreover, leak victims had higher odds for fatal outcome (16 of 49 vs 33 of 307; odds ratio, 5.94; 95% confidence interval, 2.65 to 13.15; P < 0.0001). The leakage was amendable by endoscopic stenting in 29 cases, whereas rethoracotomy was mandatory in 20 patients. Between stent and rethoracotomy cases, we observed no significant differences in age, ASA score, neoadjuvant therapy, occurrence of pneumonia, pleural empyema, or tracheostomy rate. Rethoracotomy patients sustained more often sepsis (16 of 20 vs 14 of 29; P = 0.04) and acute renal failure (nine of 20 vs four of 29; P = 0.02) as expression of more severe septic disease. Nevertheless, there was no significant difference in mortality (seven of 29 vs nine of 20; P = 0.21). Furthermore, we observed three cases of stent-related aortic erosion with peracute death from exsanguination. Despite being the preferred treatment option, endoscopic stenting was only feasible in approximately 60 per cent of all intrathoracic leaks. The results are marred by the occurrence of deadly vascular erosion. Therefore, individualized strategies should be preferred to a general recommendation for endoscopic stenting.	esophagus
Risk stratification of patients with barrett's esophagus and low-grade dysplasia or indefinite for dysplasia.	BACKGROUND & AIMS: In patients with Barrett's esophagus (BE), low-grade dysplasia (LGD) is a risk factor for esophageal adenocarcinoma (EAC), progressing at variable rates. Patients at higher risk for progression could benefit from intervention. We assessed rates of progression of LGD and indefinite for dysplasia (IND) and risk factors for progression to high-grade dysplasia (HGD) and EAC. METHODS: We analyzed data from Cleveland Clinic Barrett's Registry on patients with BE and LGD or IND at least 1 year of follow-up from January 1, 2002 through December 31, 2012. Prevalent cases were those diagnosed at or within 1 year of the first endoscopy, and the rest were incident cases. RESULTS: Among 299 patients with BE and LGD or IND, there were 32 cases of HGD and 10 cases of EAC during a follow-up period of 1577.4 patient-years. The annual incidence rates were 2.4% (95% confidence interval [CI], 1.7%-3.3%) for HGD, 0.6% (95% CI, 0.3%-1.2%) for EAC, and 2.7% (95% CI, 1.9%-3.6%) for HGD or EAC. The rates were higher in men than in women with BE and LGD or IND. Prevalent cases were 3-fold more likely to progress than incident cases. Multifocality and nodules were associated with higher risk of progression to HGD or EAC. None of the patients with IND at index biopsy developed EAC. For every 5-year increase in age, chance of regression increased by 7% (P = .04). Also, for every 1-cm increase in BE length, probability of regression decreased by 6% (P = .016). LGD at index biopsy was associated with 56% lower chance of regression compared with IND (P < .001). CONCLUSIONS: On the basis of a database analysis of patients with BE, prevalent LGD, male sex, multifocality, and nodules were associated with higher risk for progression to EAC. Older age at LGD diagnosis, IND at index biopsy, and shorter BE length were associated with regression. These findings help in risk stratification of patients with BE and LGD or IND.	esophagus
Lead structures for applications in photodynamic therapy. 5. Synthesis and biological evaluation of water soluble phosphorus(V) 5,10,15,20-tetraalkylporphyrins for PDT.	Improved photosensitizers for use in photomedicine must possess good water-solubility and optimal photophysical properties. Phosphorus(V) porphyrins fulfill these criteria and are a class of porphyrins with significant potential applications in phototherapy. Five phosphorus(V) porphyrins bearing alkyl substituents have been synthesized. Reasonable to good yields were obtained for all P(V) insertions and all compounds underwent biological evaluation for their PDT activity on two esophageal cancer cell lines, OE33 and SKGT-4. Their cellular uptake was investigated using a high content screening method. Notably, three compounds displayed good uptake and using the MTS cell proliferation assay, two were shown to have photocytotoxicity comparable to mTHPC (Temoporfin(®)) with IC50 values of 6.5 and 5.5 μM.	esophagus
The microRNAs as prognostic biomarkers for survival in esophageal cancer: a meta-analysis.	OBJECTIVES: We performed this meta-analysis to summarize all the results from available studies, aiming delineating the prognostic role of miRNA in esophageal cancer. DESIGN AND METHODS: We searched the electronic databases PubMed, EMBASE, and ISI Web of Science without time restrictions for the correlative literature to aggregate the survival results. Relevant data were extracted from studies investigating the relationship between miRNAs expression and survival in esophageal cancer patients. Pooled hazard ratios of miR-21 and miR-375 for OS in ESCC were calculated. RESULTS: A total of 25 studies involving 2,258 subjects analyzed the relationship between miRNA and prognosis of EC. In all, thirty-nine miRNAs associated with prognosis were reported in these studies. The pooled HR of higher miR-21 expression compared with lower miR-21 expression in ESCC was 1.84 (95% CI: 1.41-2.40, P < 0.001), which could significantly predict poorer OS in ESCC. Besides, higher miR-375 was also a significant predictor for OS in ESCC, with a pooled HR of 0.55 (95% CI: 0.42-0.72, P < 0.001). CONCLUSIONS: Our results support that miR-21 and miR-375 have a prognostic role in ESCC and may be useful therapeutic targets for the treatment of ESCC and meticulous follow-up for early detection of recurrence.	esophagus
A single-center experience of endoscopic submucosal dissection performed in a Western setting.	BACKGROUND: Compared with the piecemeal resection associated with endoscopic mucosal resection, endoscopic submucosal dissection (ESD) enables en bloc resection of larger lesions, allows for more accurate histological assessments, and has reduced recurrence rates. ESD is not widely performed in Western countries given increased technical difficulty, high complication rates, and long procedure times. AIMS: To evaluate the safety and efficacy of ESD in a single center in the USA. METHODS: A retrospective study on a prospectively collected database identified cases in which a single operator (IW) performed ESD at a tertiary referral center. Twenty cases were identified, nine in the upper digestive tract (four esophagus and five stomach) and 11 in the lower digestive tract (nine rectal and two sigmoid colon). Data regarding lesion location, pathology, method of ESD (composition/volume of lifting injection and resection method), post-procedure complications, and margin involvement were collected. RESULTS: En bloc resection was obtained in 14/20 patients (70 %). The average procedure time was 202 min in the esophagus, 148 min in the stomach, and 106 min for lower lesions. A major complication (perforation) occurred in 1/20 cases (5 %). Complete resection was obtained in 14/20 (70 %). R0 resection was obtained in 16/20 (80 %) cases. CONCLUSIONS: The complication, en bloc resection, and complete resection rates of this study are similar to those found in large studies on ESD performed in Eastern settings. ESD is safe and efficacious for en bloc resections of pre-malignant and early-invasive lesions, and should be offered to patients with suitable lesions in Western settings.	esophagus
ErbB targeting inhibitors repress cell migration of esophageal squamous cell carcinoma and adenocarcinoma cells by distinct signaling pathways.	ErbB family receptor tyrosine kinases (ErbBs) play a role in cell adhesion and migration and are frequently overexpressed in esophageal squamous cell carcinomas (ESCCs) or esophageal adenocarcinomas (EACs). Targeting ErbBs by tyrosine kinase inhibitors (TKIs) may therefore limit esophageal cancer cell migration. Here, we studied the impact of TKIs on ErbB dimerization, cell signaling pathways, and cell migration in three esophageal cell lines: OE21 (ESCC), OE33 (EAC), and Het-1A (non-neoplastic esophageal epithelium). In OE21 cells, the TKIs erlotinib, gefitinib, and lapatinib slightly affected epidermal growth factor receptor EGFR/EGFR, but not EGFR/HER2 dimerization as detected by in situ proximity ligation assay (in situ PLA). Still, TKIs inhibited ERK1/2, Akt, STAT3, and RhoA activity in OE21 cells, as assessed by Western blot, antibody arrays, and Rho GTPase effector pull-down assays. This was accompanied by reduced OE21 cell migration, induction of focal adhesions, and actin cytoskeleton reorganization, as shown by Oris™ migration assay and focal adhesion kinase (FAK)/phalloidin staining. In contrast, in OE33 cells, only lapatinib decreased STAT5, Src family kinase (SFK), and FAK activity as well as β-catenin expression. This impeded cell migration and induced morphological changes in OE33 cells. No alterations were seen for the non-neoplastic Het-1A cells. Thus, we identified the ErbB signaling network as regulator of esophageal cancer cell's actin cytoskeleton, focal adhesions, and cell migration. ErbB targeted TKIs therefore also limit ESCC and EAC cell motility and migration. KEY MESSAGE: Clinical tyrosine kinase inhibitors (TKIs) reduce esophageal cancer cell migration. Loss of cell migration is linked to reduced Akt, ERK1/2, STAT (3 or 5), FAK, SFKs, and RhoA activity. Clinical TKIs act via distinct signaling in the two main histotypes of esophageal cancer.	esophagus