crossing96/oncoscreening huggingface dataset:
Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.	Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .	esophagus
Effect of trace element mixtures on the outcome of patients with esophageal squamous cell carcinoma: a prospective cohort study in Fujian, China.	BACKGROUND: The evidence about the effects of trace elements on overall survival(OS) of patients with esophageal squamous cell carcinoma(ESCC) is limited. This study aims to evaluate mixed effects of plasma trace elements on OS of ESCC. METHODS: This prospective cohort analysis included 497 ESCC patients with a median follow-up of 52.3 months. The concentrations of 17 trace elements were measured. We fitted Cox's proportional hazards regression, factor analysis and Bayesian kernel machine regression (BKMR) models to estimate the association between trace elements and OS. RESULTS: Our analysis found that in the single-element model, Co, Ni, and Cd were associated with an increased risk of death, while Ga, Rb, and Ba were associated with a decreased risk. Cd had the strongest risk effect among all elements. As many elements were found to be mutually correlated, we conducted a factor analysis to identify common factors and investigate their associations with survival time. The factor analysis indicated that the factor with high factor loadings in Ga, Ba and B was linked to a decreased risk of death, while the factor with high factor loadings in Co, Ti, Cd and Pb was associated with a borderline significantly increased risk. Using BKMR analysis to disentangle the interaction between elements in significant factors, we discovered that Ga interacted with Ba and both elements had U-shaped effects with OS. Cd, on the other hand, had no interaction with other elements and independently increased the risk of death. CONCLUSIONS: Our analysis revealed that Ga, Ba and Cd were associated with ESCC outcome, with Ga and Ba demonstrating an interaction. These findings provide new insights into the impact of trace elements on the survival of patients with ESCC.	esophagus
Erianin Impedes the Proliferation and Metastatic Migration Through Suppression of STAT-3 Phosphorylation in Human Esophageal Cancer Cells.	In this study, we have investigated erianin, a natural phenolic drug that impedes proliferation and metastatic migration through suppression of STAT-3 phosphorylation in human esophageal cancer cells. Eca-109 cells were treated with different concentrations of erianin (4, 8, 12 µM) for 24 h, and then cell proliferation, apoptosis, and metastatic markers were evaluated. Erianin-induced cytotoxicity and cell proliferation were examined using MTT and crystal violet staining techniques. The measurement of reactive oxygen species (ROS) and the study of apoptotic changes were conducted through flow cytometry. Furthermore, protein expression analyses via western blotting included an evaluation of JAK-STAT3, cell survival, cell cycle, proliferation, and apoptosis-related proteins. Moreover, erianin treatment-associated MMP expressions were studied by RT-PCR. In this study, erianin treatment induces substantial cytotoxicity and ROS production based on the concentrations in Eca-109 cells. Moreover, erianin inhibits the MAPK phosphorylation, proliferation, and metastatic protein in Eca-109 cells. STAT-3 is a crucial transcriptional factor that regulates numerous downstream proteins, such as proliferation, anti-apoptosis, and metastatic proteins. In this study, erianin treatment inhibited the protein expression of IL-6, IL-10, JAK-1, and p-STAT-3 expressions leading to induce apoptosis in Eca-109 cells. Moreover, erianin inhibited the expression of proliferation, metastatic, and anti-apoptotic markers in Eca-109 cells. Hence, erianin suppressed the JAK/STAT-3 signaling pathway and demonstrates potential as a chemotherapeutic agent for the treatment of esophageal cancer.	esophagus
Upper gastrointestinal tract microbiota with oral origin in relation to oesophageal squamous cell carcinoma.	"Introduction: Poor oral hygiene is linked to high risks of many systemic diseases, including cancers. Oral dysbiosis is closely associated with poor oral hygiene, causing tooth loss, gingivitis, and periodontitis. We provide a summary of studies and discuss the risk factors for oesophageal squamous cell carcinoma (ESCC) from a microbial perspective in this review.Methods: A literature search of studies published before December 31, 2022 from PubMed, Web of Science, and The Cochrane Library was performed. The search strategies included the following keywords: (1) oral care, oral health, oral hygiene, dental health, dental hygiene, tooth loss, teeth loss, tooth absence, missing teeth, edentulism, tooth brushing, mouthwash, and tooth cleaning; (2) esophageal, esophagus, oesophagus, and oesophageal; (3) cancer, carcinoma, tumor, and neoplasm.Discussion: Poor oral health, indicated by infrequent tooth brushing, chronic periodontitis, and tooth loss, has been associated with an increased risk of squamous dysplasia and ESCC. Oral microbial diversity and composition are profoundly dysregulated during oesophageal tumorigenesis. Similar to the oral microbiota, the oesophageal microbiota varies distinctly in multiple bacterial taxa in ESCC and gastric cardia adenocarcinoma, both of which have high co-occurrence rates in the ""Oesophageal Cancer Belt"". In addition, the potential roles of oncogenic viruses in ESCC have also been discussed. We also briefly explore the potential mechanisms underlying the tumor-promoting role of dysregulated microbiota for the development of therapeutic targeting strategies.Conclusion: Poor oral health is an established risk indicator of ESCC. The dysbiosis of microbiota in upper gastrointestinal tract that highly resembles the oral microbial ecosystem but with distinct features at individual sites contributes to the development and progression of ESCC."	esophagus
A Video-Based Procedure-Specific Competency Assessment Tool for Minimally Invasive Esophagectomy.	IMPORTANCE: Minimally invasive esophagectomy (MIE) is a complex procedure with substantial learning curves. In other complex minimally invasive procedures, suboptimal surgical performance has convincingly been associated with less favorable patient outcomes as assessed by peer review of the surgical procedure. OBJECTIVE: To develop and validate a procedure-specific competency assessment tool (CAT) for MIE. DESIGN, SETTING, AND PARTICIPANTS: In this international quality improvement study, a procedure-specific MIE-CAT was developed and validated. The MIE-CAT contains 8 procedural phases, and 4 quality components per phase are scored with a Likert scale ranging from 1 to 4. For evaluation of the MIE-CAT, intraoperative MIE videos performed by a single surgical team in the Esophageal Center East Netherlands were peer reviewed by 18 independent international MIE experts (with more than 120 MIEs performed). Each video was assessed by 2 or 3 blinded experts to evaluate feasibility, content validity, reliability, and construct validity. MIE-CAT version 2 was composed with refined content aimed at improving interrater reliability. A total of 32 full-length MIE videos from patients who underwent MIE between 2011 and 2020 were analyzed. Data were analyzed from January 2021 to January 2023. EXPOSURE: Performance assessment of transthoracic MIE with an intrathoracic anastomosis. MAIN OUTCOMES AND MEASURES: Feasibility, content validity, interrater and intrarater reliability, and construct validity, including correlations with both experience of the surgical team and clinical parameters, of the developed MIE-CAT. RESULTS: Experts found the MIE-CAT easy to understand and easy to use to grade surgical performance. The MIE-CAT demonstrated good intrarater reliability (range of intraclass correlation coefficients [ICCs], 0.807 [95% CI, 0.656 to 0.892] for quality component score to 0.898 [95% CI, 0.846 to 0.932] for phase score). Interrater reliability was moderate (range of ICCs, 0.536 [95% CI, -0.220 to 0.994] for total MIE-CAT score to 0.705 [95% CI, 0.473 to 0.846] for quality component score), and most discrepancies originated in the lymphadenectomy phases. Hypothesis testing for construct validity showed more than 75% of hypotheses correct: MIE-CAT performance scores correlated with experience of the surgical team (r = 0.288 to 0.622), blood loss (r = -0.034 to -0.545), operative time (r = -0.309 to -0.611), intraoperative complications (r = -0.052 to -0.319), and severe postoperative complications (r = -0.207 to -0.395). MIE-CAT version 2 increased usability. Interrater reliability improved but remained moderate (range of ICCs, 0.666 to 0.743), and most discrepancies between raters remained in the lymphadenectomy phases. CONCLUSIONS AND RELEVANCE: The MIE-CAT was developed and its feasibility, content validity, reliability, and construct validity were demonstrated. By providing insight into surgical performance of MIE, the MIE-CAT might be used for clinical, training, and research purposes.	esophagus
GNL3L promotes autophagy via regulating AMPK signaling in esophageal cancer cells.	Guanine nucleotide-binding protein-like 3-like (GNL3L), a conserved GTP-binding nucleolar protein, participates in regulating cell proliferation, and associates with tumorigenesis and poor prognosis in several kind of cancers. However, the role of GNL3L in modulating autophagy remains unclear. Here, we verified that GNL3L was higher expressed in esophageal cancer (ESCA) biopsies than that in the corresponding normal biopsies by a human ESCA tissue array. Utilizing immunoblotting and real-time PCR assays, we analyzed the expression of GNL3L in several ESCA cell lines, and it was highly expressed in KYSE410 cells and rarely expressed in KYSE150 cells, respectively. GNL3L overexpression promoted cell viability and cell proliferation in KYSE150 cells. On the contrary, silencing of GNL3L resulted in opposite phenotypes in KYSE410 cells. Furthermore, GNL3L level correlated with autophagic flux and influenced the levels of autophagy core proteins. Meanwhile, GNL3L also affected the AMPK signaling pathway, which is a pivotal signaling pathway for autophagy regulation. In the GNL3L-silenced cells, the AMPK agonist AICAR partly rescued the autophagic flux. Inversely, both pharmacologically and genetically deprivation of AMPK attenuated the autophagic flux induced by GNL3L overexpression. Moreover, AMPK activity alteration influenced the effect of GNL3L in regulating cell proliferation. Collectively, these findings suggest that GNL3L positively regulates cell proliferation and autophagy in ESCA cells via regulating the AMPK signaling, making itself a promising therapeutic target for ESCA.	esophagus
Case report of radiotherapy combined with anlotinib and immunotherapy for a patient with esophageal cancer and esophageal fistula.	"BACKGROUND: Esophageal cancer (EC) is a frequent gastrointestinal malignancy. The most common types of EC pathology worldwide are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Although surgical resection is still the main treatment modality for EC, most patients are already lost to surgery at the time of presentation due to the late stage. In recent years, the development of radiation therapy (RT) combined with targeted therapy (TT) and immunization therapy (IT) has brought more options for the treatment of EC. During radiation therapy, the radiation therapy area is very close to the trachea and esophagus, so radiation therapy may cause damage to the tissues of the trachea and esophagus, which is also known as a tracheoesophageal fistula (TF). We present the case of an EC patient who developed TF during radiation therapy and gradually improved after a combination of anlotinib and immunotherapy. METHODS: The patient was diagnosed with poorly differentiated ESCC by pathological biopsy and treated with ""lobaplatin + Tegafur Gimeracil Oteracil Porassium Capsule"" for 5 cycles. RESULTS: CT scan of the chest showed progression after treatment. During RT, the patient developed radiotherapy-related adverse effects, which were relieved by symptomatic support therapy. At the end of RT, the patient developed TF, but we chose to let the patient continue his radiation treatment plan with the anti-angiogenic drug ""anlotinib."" CONCLUSION: After radiation therapy, the patient continued to be treated with anlotinib and immunotherapy with camrelizumab, and the patient's lesion improved."	esophagus
Docetaxel-Based Neoadjuvant Chemotherapy Followed by En Bloc Resection for Esophageal Adenocarcinoma: A 15-Year Retrospective Analysis from a Regional Upper Gastrointestinal Cancer Network.	BACKROUND: Real-world, long-term survival outcomes of neoadjuvant, docetaxel-based therapy for esophageal and junctional adenocarcinoma are lacking. This study describes the long-term survival outcomes of patients with esophageal and junctional adenocarcinoma treated with neoadjuvant docetaxel-based chemotherapy and en bloc transthoracic esophagectomy. METHODS: A retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada, was performed. From January 2007 to December 2021, all patients with locally advanced (cT3 and/or N1) esophageal/Siewert I/II adenocarcinoma treated with neoadjuvant DCFx3 (Docetaxel/Cisplatin/5FU) or FLOTx4 (5FU/Leucovorin/Oxaliplatin/Docetaxel) and transthoracic en bloc esophagectomy were identified. Postoperative, pathological, and survival outcomes were compared. RESULTS: Overall, 236 of 420 patients met the inclusion criteria. Tumor location was esophageal/Siewert I/Siewert II (118/33/85), most were cT3-4 (93.6%) and cN+ (61.0%). DCF and FLOT were used in 127 of 236 (53.8%) and 109 of 236 (46.2%). All neoadjuvant cycles were completed in 87.3% with no difference between the regimens. Operative procedures included Ivor Lewis (81.8%), left thoraco-abdominal esophagectomy (10.6%) and McKeown (7.6%) with an R0 resection in 95.3% and pathological complete response in 9.7% (DCF 12.6%/FLOT 6.4%, p = 0.111). The median lymph node yield was 32 (range 4-79), and 60.6% were ypN+. Median follow-up was longer for the DCF group (74.8 months 95% confidence interval [CI] 4-173 vs. 37.8 months 95% CI 2-119, p <0.001. Overall survival was similar between the groups (FLOT 97.3 months, 78.6-115.8 vs. DCF 92.9, 9.2-106.5, p = 0.420). CONCLUSIONS: Neoadjuvant DCF and FLOT followed by transthoracic en bloc resection are both highly effective regimens for locally advanced esophageal adenocarcinoma with equivalent survival outcomes despite high disease load.	esophagus
P4HA1 expression and function in esophageal squamous cell carcinoma.	This study aimed to explore the effect of P4HA1 (prolyl 4-hydroxylase subunit α1) and its ratio on the prognosis of esophageal squamous cell carcinoma. The expression data of P4HA1 in esophageal cancer in The Cancer Genome Atlas and Genotype-Tissue Expression were collected using the public database gene expression profiling interactive analysis. The expression levels of P4HA1 were examined by immunohistochemistry. The relationship between P4HA1 expression and clinicopathological parameters was analyzed the χ2 test. Survival analysis was performed to investigate the effect of P4HA1 and its ratio on prognosis. Compared with normal esophageal mucosal epithelium, there was higher P4HA1 gene mRNA in esophageal cancer tissue. Regarding the expression level, no significant difference was observed in patients with stage I-IV esophageal cancer. Immunohistochemistry showed that P4HA1 was highly expressed in esophageal squamous cell carcinoma (68.7%), while it was negatively expressed in paracancerous tissues. There was a significant difference in expression between cancer and adjacent tissues. The expression of P4HA1 associated with the degree of tumor differentiation, site, lymph node metastasis, and tumor node metastasis stage. The prognostic factors that affected the OS (overall survival) of esophageal cancer patients were the degree of differentiation, lymph node metastasis, and P4HA1 expression. Multivariate analysis of the OS results of patients showed that lymph node metastases and P4HA1 expression were independent prognostic factors that affected the OS of esophageal cancer patients. The prognostic factors affecting the PFS (progression-free survival) of esophageal cancer patients in the univariate survival analysis were as follows: degree of differentiation, lymph node metastasis, and P4HA1 expression. In addition, multivariate analysis of the PFS results of patients showed that lymph node metastasis and P4HA1 expression were independent prognostic factors that affected the PFS of esophageal cancer patients. P4HA1 may be a novel potential biomarker for the early diagnosis, prognosis, and targeted therapy of esophageal cancer.	esophagus
A novel Fc-enhanced humanized monoclonal antibody targeting B7-H3 suppresses the growth of ESCC.	Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive tract with a low 5-year survival rate due to the lack of effective treatment methods. Although therapeutic monoclonal antibodies (mAbs) now play an important role in cancer therapy, effective targeted mAbs are still lacking for ESCC. B7-H3 is highly expressed in a variety of tumors and has emerged as a promising therapeutic target. Several mAbs against B7-H3 have advanced to clinical trials, but their development has not yet been pursued for ESCC. Here, we developed a humanized and Fc-engineered anti-B7H3 mAb 24F-Hu-mut2 and systematically evaluated its anti-tumor activity in vitro and in vivo. The 24F-Hu-mut2 was humanized and modified in Fc fragment to obtain stronger antibody-dependent cell-mediated cytotoxicity(ADCC) activity and nanomolar affinity. Furthermore, both of ESCC cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice models indicated that 24F-Hu-mut2 displayed potent in vivo anti-tumor activity. In addition, a computational docking model showed that the mAb bound to IgC1 and IgC2 domain of B7-H3, which is closer to the cell membrane. Consistently, our ELISA results verified the binding of 24F-Hu-WT and IgC1 and IgC2. Our results indicate that 24F-Hu-mut2 has significant anti-ESCC activity both in vitro and in vivo, and this monoclonal antibody may be a promising antibody against ESCC and other B7-H3 overexpressing tumors.	esophagus
A Novel Therapeutic Method in Gastro-esophageal Reflux Disease.	BACKGROUND: Gastro-esophageal reflux disease (GERD/GORD) is a chronic condition in which gastric acid flows backwards up into the esophagus, causing heart burn and a higher disposition to esophageal cancer. The reflux is caused by impairment of the lower esophageal sphincter (LES). Over the past century gastro-esophageal reflux has become the principal gastrointestinal condition of our time. The proton pump inhibitor class of drugs is effective in ameliorating the symptoms of reflux. The cost of investigation of patients in Europe is €100 billion per annum. The cost in days lost from work is €100 billion per annum in Europe. The global cost is 3 times this amount. METHODOLOGY: The proposed device for treating gastro-esophageal reflux is a biodegradable valve that is placed non surgically in the esophago-gastric junction to prevent reflux from the stomach to the esophagus. EXPERIMENT RESULTS: 50 simulator studies were performed with the patented device to elucidate the most consistent method of insertion and fixation in a human like simulator. The simulator was designed to replicate the normal human gastro-esophageal anatomy and characteristics. Four animal insertions were performed under ethical regulation at Amsterdam Medical Centre, Netherlands. Three cadaveric experiments were performed at Hackensack University Hospital, New Jersey, USA, to verify the positive outcomes of the simulator studies. CONCLUSION: Successful outcomes of simulator studies and cadaveric experiments allowed the design freeze of a NoReflux device for treating gastro-esophageal reflux disease.	esophagus