crossing96/oncoscreening huggingface dataset:
[RgpB contributes to chemoresistance in esophageal squamous cell carcinoma by preventing Cx43 degradation via inhibiting autophagosome-lysosome fusion].	OBJECTIVE: To investigate the mechanism through which RgpB, a virulence factor of Porphyromonas gingivalis (Pg), induces chemoresistance in esophageal squamous carcinoma. METHODS: The autophagy-regulating factors that interact with RgpB were screened by immunoprecipitation-mass spectrometry. The interaction between RgpB and the autophagy regulator TBC1D5 was investigated using co-immunoprecipitation. The impact of Pg infection on the expression of esophageal cancer cell membrane receptor molecule Cx43 was assessed using Western blotting. Immunofluorescence assay was used to analyze the relationship among Lamp1, Cx43 and TBC1D5. The effect of Pg infection on autophagosome-lysosome fusion was evaluated using autophagy double fluorescence technique. The effects of Pg infection and a Cx43 inhibitor on proliferation of esophageal cancer cells after chemotherapy were examined with plate cloning assay and CCK-8 method. RESULTS: Immunoprecipitation-mass spectrometry identified TBC1D5 as an autophagy regulator interacting with RgpB, and coimmunoprecipitation suggested that RgpB could directly bind to TBC1D5. In Pg-infected esophageal cancer cells, the expression of Cx43 on the cell membrane was significantly higher than that in non-infected cells. Immunofluorescence assay showed that the expression of Cx43 on the membrane of esophageal cancer cells increased significantly after Pg infection, which blocked autophagosome-lysosome fusion as shown by stubRFP-sensGFP-LC3 lentivirus study. Plate cloning assay and CCK-8 assay showed that the Cx43 inhibitor significantly attenuated the effect of Pg infection for promoting proliferation of esophageal cancer cells after chemotherapy. CONCLUSION: Pg infection in esophageal cancer blocked autophagosome-lysosome fusion in the tumor cells, thereby preventing Cx43 from lysosomal degradation and leading to chemoresistance of esophageal cancer.	esophagus
Definition and Predictors of Early Recurrence in Neoadjuvantly Treated Esophageal and Gastroesophageal Adenocarcinoma: a Dual-Center Retrospective Cohort Study.	ABSTARCT: BACKGROUND: Early recurrence after esophagectomy is often used as a surrogate for aggressive tumor biology and treatment failure. However, there is no standardized definition of early recurrence, and predictors for early recurrence are unknown. Therefore, we aimed to define an evidence-based cutoff to discriminate early and late recurrence and assess the influence of neoadjuvant treatment modalities for patients with esophageal or gastroesophageal-junction adenocarcinoma (EAC). PATIENTS AND METHODS: This dual-center retrospective cohort study included patients who underwent esophagectomy for stage II-III EAC after neoadjuvant treatment with chemotherapy using 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) or radiochemotherapy according to the Chemoradiotherapy for Esophageal Cancer followed by Surgery Study (CROSS) protocol from 2012 to 2022. The optimal cutoff for early versus late recurrence was calculated by using the most significant difference in survival after recurrence (SAR). Multivariable logistic regression was used to identify variables associated with early recurrence. RESULTS: Of 334 included patients, 160 (47.9%) were diagnosed with recurrence. Most patients had systemic (60.5%) or multiple sites of recurrence (21.1%), whereas local-only recurrence (9.2%) and carcinomatosis (9.2%) were rare. The optimal interval between surgery and recurrence for distinguishing early and late recurrence was 18 months (median SAR: 9.1 versus 17.8 months, p = 0.039) with only 24% of recurrences diagnosed after the calculated cutoff. Advanced pathologic tumor infiltration (ypT3-4, p = 0.006), nodal positivity (p = 0.013), poor treatment response (>10% residual tumor, p = 0.015), and no adjuvant treatment (p = 0.048) predicted early recurrence. CONCLUSION: Early recurrence can be defined as recurrent disease within 18 months. Hallmarks for early recurrence are poor response to neoadjuvant therapy with persisting advanced disease. In those patients, adjuvant therapy and closer follow-up should be considered.	esophagus
Accuracy of the preoperative estimation of esophageal invasion length of adenocarcinoma of the esophagogastric junction and its discrepancy with the pathological measurement.	PURPOSE: The incidence of esophagogastric junction (EGJ) adenocarcinoma has increased worldwide. As the EGJ is located at the boundary between the thoracic and abdominal cavities, the optimal surgical approach is a subject of debate and estimation of the esophageal invasion length (EIL) is an important factor in its selection. METHODS: Data from our in-house database were extracted for consecutive patients with Siewert type I, II and III EGJ adenocarcinoma (EIL ≤ 4 cm), who underwent transhiatal or transthoracic surgical resection between 2010 and 2016. The clinical records of these patients were reviewed and the accuracy of EIL estimation and its discrepancy with the pathological measurement were analyzed. RESULTS: A total of 82 patients were included in the final analysis. We established that EIL was underestimated in 49 of these patients (59.8%). The mean-distance discrepancy between the preoperative and pathological diagnosis of EIL in the underestimation group was 7.0 mm. Multivariate analysis revealed that submucosal cancer spread was an independent risk factor for underestimation (P < 0.01). The mean length of submucosal cancer spread was longer for undifferentiated histologic type EGJ adenocarcinomas. (P < 0.01). CONCLUSIONS: The EIL was underestimated in approximately 60% of EGJ adenocarcinomas requiring surgical treatment. Thus, careful management is necessary, especially for EGJ adenocarcinoma of the undifferentiated histologic type.	esophagus
Superficial Esophageal Neuroendocrine Carcinoma with Marked Morphological Changes in a Short Period.	A de novo whitish subepithelial lesion (SEL) with irregular vascular hyperplasia was detected in the lower thoracic esophagus during endoscopic surveillance. Special types of esophageal cancer were suspected; however, endoscopic biopsy specimens were inadequate for a diagnosis. Ten days later, endoscopic ultrasound showed a 7-mm homogeneously hypoechoic round mass in the submucosa, and a biopsy confirmed a histological diagnosis of esophageal neuroendocrine carcinoma (eNEC). Based on the clinical diagnosis of cT2N0M0, subtotal esophagectomy followed by adjuvant chemotherapy was performed immediately after endoscopic reexamination revealing a 20-mm reddish SEL. We herein report the marked changes in endoscopic findings of eNEC within 1.5 months.	esophagus
Artificial intelligence enhances the management of esophageal squamous cell carcinoma in the precision oncology era.	Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer with a poor prognosis. Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC patients. With the advancement of artificial intelligence (AI) technology and the proliferation of medical digital information, AI has demonstrated promising sensitivity and accuracy in assisting precise detection, treatment decision-making, and prognosis assessment of ESCC. It has become a unique opportunity to enhance comprehensive clinical management of ESCC in the era of precision oncology. This review examines how AI is applied to the diagnosis, treatment, and prognosis assessment of ESCC in the era of precision oncology, and analyzes the challenges and potential opportunities that AI faces in clinical translation. Through insights into future prospects, it is hoped that this review will contribute to the real-world application of AI in future clinical settings, ultimately alleviating the disease burden caused by ESCC.	esophagus
Prognostic and predictive factors for the efficacy and safety of trastuzumab deruxtecan in HER2-positive gastric or gastroesophageal junction cancer.	BACKGROUND: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting HER2-positive gastric cancer or gastroesophageal junction cancer (GC/GEJC). Although effective, T-DXd has notable toxicities, including interstitial lung disease (ILD). This study evaluated the efficacy, safety, and prognostic factors associated with T-DXd for GC/GEJC. METHODS: A retrospective observational study was conducted at our institution by reviewing medical records of patients treated with T-DXd until September 2023. Eligible patients had unresectable advanced or recurrent GC/GEJC, HER2 status of IHC 3 + or IHC 2 + /ISH-positive, and prior treatment with trastuzumab-containing regimen. RESULTS: Among the 101 patients analyzed, the initial T-DXd dose was 6.4 mg/kg in 77 patients and 5.4 mg/kg in 24 patients. The objective response rate was 54.3%, with a median PFS of 5.4 months and a median OS of 11.4 months. The significant prognostic factors for shorter PFS and OS included ECOG PS ≥ 1, presence of primary lesion, and peritoneal metastasis but not the initial T-DXd dose. ILD occurred in 14.9% of patients. Notably, higher T-DXd dose and smaller tumor burden were associated with a higher incidence of ILD. CONCLUSIONS: Several factors were associated with prognosis after T-DXd treatment in patients with GC/GEJC. Tumor burden is a potential risk factor for T-DXd-related ILD. Further studies are needed to optimize dosing based on tumor burden and to improve the therapeutic index.	esophagus
Inflammatory Burden Index Is an Independent Prognostic Factor for Esophageal Cancer Patients Who Receive Curative Treatment.	BACKGROUND/AIM: We hypothesized that the inflammatory burden index (IBI) is a promising biomarker for esophageal cancer (EC) treatment and management. To confirm our hypothesis, we evaluated the prognostic impact of IBI in patients with EC who received curative treatment. PATIENTS AND METHODS: We conducted a retrospective review of medical records and collected data from consecutive patients with EC who underwent curative resection at Yokohama City University between 2005 and 2020. The IBI score was calculated as the C-reactive protein level multiplied by the neutrophil-to-lymphocyte ratio. RESULTS: In total, 180 patients with EC were included in this study. The 3- and 5-year overall survival (OS) rates were 72.9% and 63.4%, respectively, in the IBI-low group, and 38.2% and 32.5% in the IBI-high group (p<0.001). In the multivariate analysis, IBI was identified as a significant prognostic factor for OS [hazard ratio (HR)=2.372; 95% confidence interval CI=1.478-3.806, p<0.001]. In addition, the 3- and 5-year recurrence-free survival (RFS) rates were 52.9% and 47.8%, respectively, in the IBI-low group, and 22.9% and 17.2% in the IBI-high group (p<0.001). In the multivariate analysis, IBI was identified as a significant prognostic factor for RFS (HR=2.484; 95%CI=1.373-4.494, p<0.001). When comparing the recurrence patterns between the IBI-high and IBI-low groups, there were significant differences in lymph node recurrence (46.0% vs. 26.2%, p=0.010) and hematological recurrence (52.0% vs. 18.5%, p<0.001). CONCLUSION: IBI affects both the short- and long-term oncological outcomes. Thus, IBI may be a promising prognostic factor for the treatment and management of EC.	esophagus
Exploring the clinicopathological characteristics of submucosal tumor-like esophageal squamous cell carcinoma and the diagnostic significance of endoscopic ultrasound: a comprehensive analysis.	BACKGROUND: Completely intramural growth submucosal squamous cell carcinoma of the esophagus, also known as SMT-like esophageal squamous cell carcinoma (ESCC), represents a rare and distinct form of esophageal cancer. Its white light endoscopic manifestations resemble those of esophageal subepithelial lesions, and biopsy pathology is often negative, leading to potential oversight or misdiagnosis. This study aimed to comprehensively summarize the clinicopathological and endoscopic ultrasound (EUS) characteristics of patients with SMT-like ESCC while also evaluating the immunohistochemical expression of these patient. METHODS: This study collected clinical data, including demographic and clinicopathological data, as well as EUS findings, from six patients with SMT-like ESCC. Immunohistochemical analysis was also conducted on tumor tissues to assess the expression of CK7, CK19, CK20, TTF-1, SMA, S-100, Melan-A, CD117, Mucin (MUC) 2, and MUC5. RESULTS: In EUS, SMT-like ESCC is characterized by nonuniform hypoechoic lesions with indistinct borders, often exhibiting a burr or serrated appearance. Most of these lesions involved multiple levels. Cytological specimens obtained through EUS-guided fine needle aspiration (EUS-FNA) revealed suspected squamous cell carcinoma with positive expression of CK5/6, P40, and P63, further confirming the diagnosis of ESCC. Additionally, four patients exhibited CK7+/CK20- immune-expression profiles, and all patients had positive CK19 expression. TTF-1, SMA, S-100, Melan-A, CD117, MUC2, and MUC5 were negative. CONCLUSION: Combining EUS with EUS-FNA is a valuable approach for diagnosing and differentiating SMT-like ESCC. Furthermore, the characteristic CK7+/CK20- immune profile suggested a potential origin from the esophageal submucosa glands.	esophagus
Comparative Evaluation of Dosimetric Quality and Treatment Efficiency for Halcyon, TrueBeam, and TomoTherapy in Cervical-Thoracic Esophageal Cancer Radiotherapy.	INTRODUCTION: This study primarily aims to investigate the suitability of Halcyon in the context of cervical-thoracic esophageal cancer by exploring the dosimetric quality and delivery efficiency of Halcyon plans with different arc configurations. Additionally, it compares these findings with the dosimetric indices and delivery efficiency of TrueBeam and TomoTherapy accelerators, focusing on their capability to optimize protection for organs at risk (OARs) while maintaining efficient treatment delivery strategies. METHODS: This retrospective study involved 26 patients diagnosed with cervical-thoracic esophageal cancer, and new radiotherapy plans were created using Halcyon, TrueBeam, and TomoTherapy. Dose volume histogram (DVH) metrics and delivery efficiency for plans involving different arc numbers on Halcyon (2, 3, and 4 arcs) were compared with those from TrueBeam and TomoTherapy. T-tests were employed to evaluate differences in organ protection among the accelerators. RESULTS: The Halcyon plans, especially those with 4 arcs, provided superior protection for organs at risk, including the heart, lungs, and spinal cord, while maintaining excellent delivery efficiency. Compared to TrueBeam 2arc plans and TomoTherapy helical plans, Halcyon plans with 3 arcs also showed slight advantages. Although TomoTherapy offered better uniformity in dose distribution, it did not demonstrate a clear advantage over the other accelerators in terms of OAR protection or treatment efficiency. Furthermore, despite the lack of clear advantages in TrueBeam 2arc plans with flattening filter (FF), TrueBeam with flattening filter free (FFF) plans may hold potential in the treatment. CONCLUSION: Halcyon, particularly with 4 arcs, offers an optimal balance between reducing toxicity to organs at risk and maintaining treatment efficiency, making it a preferred choice in cervical thoracic esophageal cancer radiotherapy. The findings highlight the need for careful selection of radiotherapy accelerators based on specific clinical goals, with Halcyon showing potential advantages in scenarios where both treatment efficiency and OAR protection are paramount.	esophagus
Indirect Immunofluorescence Test for Detecting HSV-1, 2 in Patients with Esophageal Cancer: A Pilot Cross-Sectional Survey in Kazakhstan.	OBJECTIVE: To evaluate the detectability of herpes simplex virus type 1 and 2 (HSV-1, 2) antigens in the esophageal mucosa in esophageal cancer. METHODS: A cross-sectional pilot study with a control group was conducted from December 2022 to May 2023. The patients were divided into two groups: the main group with verified esophageal cancer and the control group without esophageal cancer based on the histological report. Diagnosis using fibroesophagogastroscopy (FEGS), histological analysis, and indirect immunofluorescence reaction (iIFR) was accomplished according to indications at the outpatient center of the endoscopic department of the Multidisciplinary Medical Center, Astana. Descriptive statistics and nonparametric methods were used to analyze the data. RESULT: A total of 30 patients were recruited in the study, with 15 patients in the main group and 15 patients in the control group. HSV-1 and HSV-2 antigens were detected in the 13 cases (86.7%) during the study of biomaterial from patients with confirmed esophageal cancer in the main group and only in one case (6.8%) in the control group (95% CI 7.35 - 1126.9%, p=0.001). The presence of lymphocytic infiltration was detected in 13 cases (86.7%) in the main group and in 5 cases (33.3%) in the control group (95% CI 2.07 - 81.48%, p = 0.008). The process of keratinization was identified in HSV-1,2 antigens positive cases in the main group in 5 cases (35.7%) G1, in 5 cases (35.7%) G2, and in 3 cases (21.4 %) G3 (95% CI 1.66 - 656.23%, p=0.002). CONCLUSION: Overall, the local activity of herpesvirus infection to a certain extent influences the malignant potential of tumor cells and the resistance of surrounding healthy tissues. A large-scale study is still needed to confirm these results. The present pilot study provided an overview of a possible method for detecting HSV-1,2 activity in malignant tissue from esophageal cancer.	esophagus
Association of Non-Tobacco Products (NTP) with Oral, Esophageal, and Pharyngeal Cancer and Oral Potentially Malignant Disorders (OPMD) in Adults: A Systematic Review and Meta-Analysis.	INTRODUCTION: Non-tobacco products (NTP) are increasingly popular as an alternative to traditional tobacco use, raising concerns about potential health risks. This systematic review and meta-analysis examine the association of NTP use with oral, esophageal, & pharyngeal cancer, and oral potentially malignant disorders (OPMD) in adults. METHODS: A comprehensive electronic search was conducted in PubMed, Embase, and Google Scholar, for observational studies that evaluated the association between NTP use, and oral, esophageal, & pharyngeal cancer and OPMD, published till December 2023 in the English language. The quality of the included studies was assessed using the Newcastle-Ottawa scale. Pooled odds ratio (OR) with a 95% Confidence Interval (CI) was obtained using a random effects model, heterogeneity was assessed using I2 statistic. Sub-group analysis was conducted based on the year of publication, a comparator for association, type of NTP user, and country. RESULTS: Forty-nine studies were included in the meta-analysis with a combined total of 1,32,390 participants, revealing a significant association between NTP use and increased risk of cancers- oral (OR:5.0, 95% CI 3.3-7.7), esophageal (OR:3.0, 95%CI 1.2-7.5), and OPMD (OR:15.3, 95%CI 8.8-26.7). The proportion of the annual burden of oral and esophageal cancers attributable to NTP was 33% (30,667 cancers), and 19% (8,025 cases) respectively in India. CONCLUSION: This review provides strong evidence for the association between NTP use and increased risk of oral, and esophageal cancer and OPMD. The findings highlight the need for targeted interventions, firmer regulations, and awareness campaigns addressing NTP. Incorporating NTP as a separate category in national surveys can help reduce their burden, particularly in high-risk populations.	esophagus
Esophageal cancer risk is influenced by genetically determined blood metabolites.	It remains unclear what causes esophageal cancer (EC), but blood metabolites have been connected to it. Our study performed a Mendelian randomization (MR) analysis to assess the causality from genetically proxied 1400 blood metabolites to EC level. A two-sample MR analysis was employed to evaluate the causal relationship between 1400 blood metabolites and EC. Initially, the EC genome-wide association study (GWAS) data (from Jiang L et al) were examined, leading to the identification of certain metabolites. Subsequently, another set of EC GWAS data from FINNGEN was utilized to validate the findings. Causality was primarily determined through inverse variance weighting, with additional support from the MR-Egger, weighted median, and MR-PRESSO models. Heterogeneity was assessed using the MR Cochran Q test. The MR-Egger intercept and MR-PRESSO global methods were employed to detect multicollinearity. In this study, Bonferroni corrected P value was used for significance threshold. We found 2 metabolites with overlaps, which are lipids. Docosatrienoate (22:3n3) was found to be causally associated with a decreased risk of EC, as evidenced by the EC GWAS data (from Jiang et al) (odds ratio [OR] = 0.620, 95% confidence interval [CI] = 0.390-0.986, P = .044) and the EC GWAS data (from FINNGEN) (OR = 0.77, 95% CI = 0.6-0.99, P = .042), these results were consistent across both data sets. Another overlapping metabolite, glycosyl-N-(2-hydroxyneuramoyl)-sphingosine, was associated with the risk of ES, with EC GWAS data (from Jiang L et al) (OR = 1.536, 95% CI = 1.000-2.360, P = .049), while EC GWAS data (from FINNGEN) (OR = 0.733, 95% CI = 0.574-0.937, P = .013), the 2 data had opposite conclusions. The findings of this study indicate a potential association between lipid metabolites (Docosatrienoate (22:3n3) and glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18:1/24:1 (2OH))) and the risk of esophageal carcinogenesis.	esophagus
Homologous recombination deficiency score is an independent prognostic factor in esophageal squamous cell carcinoma.	Homologous recombination deficiency (HRD) represents an impairment in the homologous recombination repair (HRR) pathway, crucial for repairing DNA double-strand breaks and contributing to genomic instability in cancer. The HRD score may be a more reliable biomarker than HRR-related gene mutations for identifying patients sensitive to poly(ADP-ribose) polymerase inhibitors. Despite its relevance in various cancers, the HRD score remains underexplored in esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed HRD scores in 96 ESCC patients, examining correlations with clinical characteristics and survival outcomes, and validated our findings using the TCGA dataset. Genomic sequencing utilized a custom superHRD next-generation sequencing panel, and HRD scores were calculated from 54,000 single-nucleotide polymorphisms using Kruskal-Wallis rank-sum tests and two cut-off points for analysis. Higher HRD scores correlated with advanced tumor stages, recurrence, and mutations in TP53 and ABCB1, while APC mutations were linked to lower HRD scores. Patients with high HRD scores had significantly shorter disease-free survival (p = 0.013) and a trend toward shorter overall survival (OS) (p = 0.005), particularly those not receiving adjuvant therapy. Conversely, HRD-high patients undergoing adjuvant therapy showed a trend toward longer OS (p = 0.015). Multivariate analysis identified HRD as an independent prognostic factor (hazard ratio = 2.814 for recurrence, p = 0.015). Validation with the TCGA dataset supported these findings. This study highlights the associations between HRD scores, clinical characteristics, and genomic mutations in ESCC, suggesting HRD as a potential prognostic biomarker. HRD assessment may aid in patient stratification and personalized treatment strategies, warranting further investigation to validate the therapeutic implications of HRD scores in ESCC.	esophagus