Combined deep learning and radiomics in pretreatment radiation esophagitis prediction for patients with esophageal cancer underwent volumetric modulated arc therapy.

PURPOSE: To develop a combined radiomics and deep learning (DL) model in predicting radiation esophagitis (RE) of a grade ≥ 2 for patients with esophageal cancer (EC) underwent volumetric modulated arc therapy (VMAT) based on computed tomography (CT) and radiation dose (RD) distribution images. MATERIALS AND METHODS: A total of 273 EC patients underwent VMAT were retrospectively reviewed and enrolled from two centers and divided into training (n = 152), internal validation (n = 66), and external validation (n = 55) cohorts, respectively. Radiomic and dosiomic features along with DL features using convolutional neural networks were extracted and screened from CT and RD images to predict RE. The performance of these models was evaluated and compared using the area under curve (AUC) of the receiver operating characteristic curves (ROC). RESULTS: There were 5 and 10 radiomic and dosiomic features were screened, respectively. XGBoost achieved a best AUC of 0.703, 0.694 and 0.801, 0.729 with radiomic and dosiomic features in the internal and external validation cohorts, respectively. ResNet34 achieved a best prediction AUC of 0.642, 0.657 and 0.762, 0.737 for radiomics based DL model (DLR) and RD based DL model (DLD) in the internal and external validation cohorts, respectively. Combined model of DLD + Dosiomics + clinical factors achieved a best AUC of 0.913, 0.821 and 0.805 in the training, internal, and external validation cohorts, respectively. CONCLUSION: Although the dose was not responsible for the prediction accuracy, the combination of various feature extraction methods was a factor in improving the RE prediction accuracy. Combining DLD with dosiomic features was promising in the pretreatment prediction of RE for EC patients underwent VMAT.

Screening of genes related to programmed cell death in esophageal squamous cell carcinoma and construction of prognostic model based on transcriptome analysis.

OBJECTIVES: To screen programmed cell death (PCD)-related genes in esophageal squamous cell carcinoma (ESCC) based on transcriptomic data and to explore its clinical value. METHODS: Differentially expressed PCD genes (DEPCDGs) were screened from ESCC transcriptome and clinical data in TCGA database. Univariate COX and LASSO COX were performed on prognostically DEPCDGs in ESCC to develop prognostic model. Differences in immune cell infiltration in different RiskScore groups were determined by ssGSEA and CIBERSORT. The role of RiskScore in immunotherapy response was explored using Tumor Immune Dysfunction and Exclusion (TIDE) and IMvigor210 cohorts. RESULTS: Fourteen DEPCDGs associated with prognosis were tapped in ESCC. These DEPCDGs form a RiskScore with good predictive performance for prognosis. RiskScore demonstrated excellent prediction accuracy in three data sets. The abundance of M2 macrophages and Tregs was higher in the high RiskScore group, and the abundance of M1 macrophages was higher in the low RiskScore group. The RiskScore also showed good immunotherapy sensitivity. RT-qPCR analysis showed that AUP1, BCAP31, DYRK2, TAF9 and UBQLN2 were higher expression in KYSE-150 cells. Knockdown BCAP31 inhibited migration and invasion. CONCLUSION: A prognostic risk model can predict prognosis of ESCC and may be a useful biomarker for risk stratification and immunotherapy assessment.

Unveiling esophageal cancer treatment mechanisms: network pharmacology and molecular docking of Physcion.

This study investigates the effects of Physcion on esophageal cancer and its possible mechanisms of action. Potential Physcion targets were identified using databases. Transcriptomic data from 17 esophageal cancer and adjacent tissues were analyzed to find differentially expressed genes, intersecting with potential targets to select 16 key genes. Their expression and distribution were evaluated in patient sequencing data. Diagnostic potential was assessed through differential gene expression and ROC curves. Pathway enrichment analysis was performed using KEGG, and molecular docking simulations were conducted to assess Physcion's binding affinity to key genes. In vitro assays complemented these findings. A total of 161 drug targets were identified, narrowing down to 16 pivotal genes. Expression patterns were examined across cell populations, and enrichment analysis showed significant PI3K/AKT pathway involvement. Molecular docking indicated strong binding of Physcion to HSP90AA1 and MMP2. In vitro assays confirmed Physcion's dose- and time-dependent impact on esophageal cancer cells, with significant DAPI staining effects. Physcion shows promise as a therapeutic agent for esophageal cancer. The study supports its potential for clinical development and future research in esophageal cancer treatment.

The Right Gastroepiploic Artery as a Potential Organ at Risk in Neoadjuvant Chemoradiation for Esophageal and Gastroesophageal Cancers.

BACKGROUND: Preoperative chemoradiation is a standard of care for esophageal and gastroesophageal cancer. A gastric conduit is usually used for anastomosis with the right gastroepiploic artery (RGEA) being the sole arterial supply to the gastric remnant after such surgeries. Hence, lowering the radiation dose to this vessel may lower the risks of postoperative complications related to poor vasculature. Herein, we report our experience in contouring and replanning cases of distal esophageal/gastroesophageal carcinomas so that the radiation doses to the RGEA could be minimized. MATERIALS AND METHODS: Radiation plans of patients with lower esophageal/gastroesophageal carcinomas were retrieved from our database. Identification and delineation of the RGEA was done and replanning was performed with the aim to keep the maximal and mean doses as well as the V10Gy and V20Gy of the RGEA as low as possible without compromising target volume coverage.  Results: We achieved significant dose reductions in most of the dosimteric parameters in our selected cases without compromising target coverage. CONCLUSION: Lowering the dose to the RGEA, a potential organ-at-risk that may impact the postoperative course after neoadjuvant chemoradiation, is feasible.

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

Association between preoperative serum zinc level and prognosis in patients with advanced esophageal cancer in the neoadjuvant treatment era.

Background: Zinc (Zn), an essential trace element, has an adverse influence on the prognosis of several cancers. However, the association between the preoperative serum Zn level and outcomes in patients with advanced esophageal cancer in the current neoadjuvant treatment era remains unclear. Methods: This study involved 185 patients with esophageal cancer who underwent R0 surgery after neoadjuvant chemotherapy from August 2017 to February 2021. We retrospectively investigated the relationship between the preoperative serum Zn level and the patients' outcomes. Results: The patients were divided into a low Zn group (<64 µg/dL) and a high Zn group (≤64 µg/dL) according to the mean preoperative serum Zn level. Low Zn had significantly worse overall survival (OS) (2-year OS rate: 76.2% vs. 83.3% in low vs. high Zn; p = 0.044). A low Zn in pathological non-responders (Grade ≤ 1a) was significantly associated with a shorter 2-year recurrence-free survival (RFS) rate (39.6% vs. 64.1% in low vs. high Zn; p = 0.032). The multivariate analysis identified low BMI and Zn level among preoperative nutritional status indices as an independent risk factor for worse RFS in non-responders. Compared with responders, pathological non-responders comprised significantly more males and a performance status of ≥1, and there was no difference in Zn level according to pathological response. Conclusion: A preoperative low Zn level had a negative impact on early recurrence in esophageal cancer patients who underwent neoadjuvant chemotherapy. This suggests the need to administer Zn supplementation to patients with esophageal cancer who have preoperative Zn deficiency.

Multicenter retrospective analysis of complications and risk factors in endoscopic resection for esophageal cancer across Japan.

BACKGROUND: Endoscopic resection (ER) is a minimally invasive treatment for esophageal cancer that sometimes causes complications. To understand the real-world incidence and risk factors for these complications, a nationwide survey was conducted across Japan. METHODS: This retrospective multicenter study included patients who underwent ER for esophageal cancer from April 2017 to March 2018 (2017 complication analysis) and April 2021 to March 2022 (2021 complication analysis). The study assessed the complication rates and conducted risk factor analyses for endoscopic submucosal dissection (ESD) using data for these patients, with exclusions based on specific criteria to ensure data accuracy. RESULTS: In the 2021 complication analysis, there were two mortalities highly likely attributable (0.03%) to ER and one mortality possibly attributable (0.01%) to ER. Intraoperative perforation, delayed bleeding, and pneumonia occurred in 137 cases (1.8%), 44 cases (0.6%), and 130 cases (1.7%), respectively. In the multivariate analysis for complications after ESD, low ER volume of the facility was an independent risk factor for perforation, while lesion location in the cervical or upper thoracic esophagus was an independent factor for reduced risk of perforation. Age ≥ 80 years was a risk factor for pneumonia, while use of traction techniques was a factor for reduced risk of pneumonia. Lesions located in the middle thoracic esophagus had a lower risk of stricture, and the risk of stricture increased as the circumferential extent of the lesion increased. CONCLUSIONS: This large-scale study provided detailed insights into the complications associated with esophageal ER and identified significant risk factors.

Angiopoietin-Like Protein 2 Expression in Tumor Cells Supports Tumor-Associated Macrophage-Induced Tumor Progression in Esophageal Cancer.

BACKGROUND: Tumor-associated macrophages (TAM), a major component of the tumor microenvironment, play key roles in tumor formation and progression; however, mechanisms underlying TAM-induced tumor progression are complex and not well known. We previously reported that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) functions as a tumor promoter in some cancer contexts. METHODS: We examined ANGPTL2 expression in paraffin-embedded tumor samples from resected specimens of 221 patients with esophageal cancer. Patients were subdivided into four groups based on immunohistochemistry scores described above: ANGPTL2-low/TAM-low, ANGPTL2-low/TAM-high, ANGPTL2-high/TAM-low, and ANGPTL2-high/TAM-high groups. Gene expression datasets of esophageal cancer cell lines were obtained from the cancer cell line encyclopedia public database. RESULTS: In this study, we demonstrate that TAM infiltration is associated with poor prognosis in patients with esophageal cancer whose tumor cells show relatively higher ANGPTL2 expression levels; however, TAM infiltration did not affect prognosis in patients with ANGPTL2-low-expressing esophageal cancer, suggesting that ANGPTL2 expression in esophageal cancer cells is required for TAM-induced tumor progression. Our analysis of public datasets indicates a potential positive correlation of ANGPTL2 expression levels with that of transforming growth factor (TGF)-ß, a TAM-activating factor, in esophageal cancer cell lines. CONCLUSION: We conclude that ANGPTL2 signaling in tumor cells supports TAM-induced tumor progression and contributes to poor prognosis in patients with esophageal cancer. These findings overall provide novel insight into pro-tumor ANGPTL2 functions and illustrate the essential role of cancer cell/TAM crosstalk in cancer progression.

Hot beverage consumption in the African Esophageal Cancer Corridor: A community-based thermal exposure measurement study across the lifespan.

"Very hot beverage" (>65°C) consumption is an IARC probable carcinogen and may contribute to the African esophageal cancer burden. We conducted community cross-sectional exposure studies of hot beverage consumption in Kenya and Malawi during 2018-2019, aiming to: (i) implement a detailed measurement protocol incorporating three measurements of sip temperature and volume so as to predict each sip's intra-esophageal liquid temperature (IELT); (ii) examine variations by seasonality, drinking venue and age, including children. 246 participants were included, of whom 236 had drink measurements (52 children and 183 adults). Among adults, mean (SD) temperatures at first sip were 67 (9) and 68 (7) °C in Kenya and Malawi respectively, i.e. 58 and almost 70 % of first sips were > 65 °C. In both countries, adults exhibited a protective habit of smaller sips at higher temperatures (mean 11 mL at first sip), whereas the larger middle sip (20 mL) had the highest IELT (45 °C). The highest temperatures were observed in men and for drinks taken in social settings, whereas we did not detect seasonality or associations with other esophageal cancer risk factors. Measurements were difficult to make for 20 % (8/43) of Kenyan children whose drink was cooled by pouring between cups ('poesha'). Where poesha was not practiced, IELTs were lower in children (especially < 10 years) than in adults, owing to a mean of 8 °C cooler first sip temperature, however 20 % of first sips were > 65 °C. If very hot beverage consumption is an esophageal carcinogen, lowering sip temperatures and volumes in East Africa would form important prevention avenues.

Response to chemotherapy could predict the prognosis of esophageal squamous cell carcinoma treated with neoadjuvant docetaxel, cisplatin, and fluorouracil (DCF) followed by surgery: long-term results in a single institute.

BACKGROUND: Preoperative chemotherapy with 5-fluorouracil and cisplatin (FP) followed by surgery has been considered a standard treatment for patients with stage II/III esophageal squamous cell carcinoma (ESCC) based on the results of a phase III trial (JCOG9907) in Japan. Subsequently, the phase III NExT trial (JCOG1109) revealed the survival benefit of the neoadjuvant DCF regimen, which adds docetaxel to FP, and it became a standard treatment. However, the long-term results and prognostic factors of neoadjuvant DCF therapy in the real world are unknown. METHODS: We retrospectively investigated 50 patients with ESCC treated with neoadjuvant DCF therapy from July 2012 to December 2017 at The University of Tokyo Hospital. RESULTS: Median overall survival (OS) and progression-free survival (PFS) were 32.3 [95% confidence interval (CI) 21.0-NA] and 10.0 months (95% CI 6.3-15.6), respectively. Median OS [not reached (95% CI 31.5-NA) vs. 21.4 months (95% CI 13.5-33.0); p = 0.028] and PFS [83.3 months (95% CI 6.4-NA) vs. 7.4 months (95% CI 6.0-12.8] were significantly longer in patients with an objective response than in non-responders. Of 44 surgical cases, median PFS tended to be longer in pathological lymph node metastasis-negative patients. Conversely, survival did not differ according to cStage (II/III vs. IV) or the average relative dose intensity (ARDI, ≥ 85% vs. < 85%). DISCUSSION: The response to neoadjuvant DCF therapy could predict patient prognosis. Additionally, pN+ tended to increase the recurrence risk, whereas cStage and ARDI did not influence survival.

Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy for resectable esophageal cancer: a systematic review and meta-analysis.

Background: Esophageal cancer is often overlooked in its early stages, with approximately 70% of patients being diagnosed at a locally advanced or late stage. Surgical treatment and chemotherapy are the mainstays of esophageal cancer management. However, for locally advanced esophageal cancer, both surgery alone and chemotherapy alone have high rates of recurrence and metastasis. The objective of the research was to investigate the security and therapeutic efficacy of neoadjuvant immunochemotherapy (NICT) in the treatment of resectable, locally advanced esophageal squamous cell carcinoma (ESCC). Methods: We conducted a literature search on PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), China Biomedical Literature Database, and Wanfang for studies published before November 2023 that investigated on the clinical effectiveness and safety of neoadjuvant immunotherapy in resectable ESCC. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used for assessment, and Stata 17.0 was utilized for meta-analysis and sensitivity analysis. Results: A total of 13 retrospective cohort studies involving 1,276 patients were included in this analysis. The NICT group showed a higher pathological complete response (pCR) rate [odds ratio (OR) =5.72; 95% confidence interval (CI), 3.40-9.63]. The major pathologic response (MPR) rate, objective response rate (ORR), R0 resection rate, and 1-year overall survival (OS) in the NICT group were better than those in the neoadjuvant chemotherapy (NCT) group (OR =3.70, 95% CI: 2.32-5.91; OR =2.22, 95% CI: 1.44-3.40; OR =2.63, 95% CI: 1.58-4.38; OR =10.08, 95% CI: 4.32-23.56). However, the NICT group also showed a drawback in terms of adverse reactions and postoperative complications. The incidence of rash (OR =4.69, 95% CI: 1.42-15.49) and pleural effusion (OR =3.99, 95% CI: 1.75-9.07) was significantly higher in the NCT group compared to the NICT group. The subgroup analysis indicates that the use of camrelizumab is associated with an increased incidence of rash. Additionally, performing a left thoracic esophagectomy and esophagogastric thoracic procedure significantly improved the R0 resection rate. Conclusions: Neoadjuvant immunotherapy has shown promising efficacy in patients with locally advanced ESCC; however, it is linked to a higher occurrence of adverse events. Therefore, its use in clinical practice should be carefully considered.

Combining non-invasive liquid biopsy and a methylation analysis to assess surgical risk for early esophageal cancer.

Background: While the widespread use of endoscopic submucosal dissection (ESD) has significantly reduced the incidence of early esophageal cancer (ESCA), the limited ability of ESD to strip deep infiltrating esophageal lesions results in a considerable risk of intraoperative perforation. Circulating-free DNA (cfDNA) is widely used in modern tumor screening due to its non-invasive detection capabilities. A methylation analysis offers vital insights into the condition and advancement of malignancies due to its unique positioning, such as a marker of cancer. This study investigated the potential of combining a non-invasive liquid biopsy technique, along with a methylation analysis, to assess the surgical perforation risk of ESCA patients. Methods: In this study, we conducted an analysis of gene expression differences between stage I esophageal squamous carcinoma samples and healthy tissue samples using data from The Cancer Genome Atlas (TCGA) database. We also identified the genes associated with progression-free survival (PFS) in esophageal squamous carcinoma. Integrating the framework of the methylation analysis, we explored the methylated sites of these distinct genes. To refine this process, we used the Shiny Methylation Analysis Resource Tool (SMART) to conduct a comprehensive analysis of these sites. We then confirmed the stability of the methylation sites in different lesion conditions using methylation-specific quantitative polymerase chain reaction (MS-qPCR) with paraffin tissue samples collected after ESD. Results: We analyzed RNA-sequencing data from 42 early stage ESCA patients and 17 controls, identifying 1,263 up-regulated and 460 down-regulated genes. Functional analyses revealed involvement in key pathways such as cell cycle regulation and immune responses. Furthermore, we identified 38 differentially expressed genes associated with PFS. Using SMART analysis, we found 217 hyper-methylated regions in 38 genes, suggesting potential early markers for ESCA. Validation experiments confirmed the reliability of 29 hyper-methylated regions in FFPE tissue samples and 6 regions in cfDNA. A LunaCAM model showed high accuracy [area under the curve (AUC) =0.89] in discriminating early ESCA. Integrated assessment of six highly methylated regions significantly improved predictive performance, with 90.56% sensitivity, highlighting the importance of combinatorial biomarker evaluation for early cancer detection. Conclusions: This study established a novel approach that integrates non-invasive testing with a methylation analysis to assess the surgical risk of early ESCA patients. The significance of changes in methylation sites in relation to lesion status should not be underestimated, as they have the potential to offer vital insights for proactive risk assessments before surgery.

Metabolic reprogramming in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a malignancy with high incidence in China. Due to the lack of effective molecular targets, the prognosis of ESCC patients is poor. It is urgent to explore the pathogenesis of ESCC to identify promising therapeutic targets. Metabolic reprogramming is an emerging hallmark of ESCC, providing a novel perspective for revealing the biological features of ESCC. In the hypoxic and nutrient-limited tumor microenvironment, ESCC cells have to reprogram their metabolic phenotypes to fulfill the demands of bioenergetics, biosynthesis and redox homostasis of ESCC cells. In this review, we summarized the metabolic reprogramming of ESCC cells that involves glucose metabolism, lipid metabolism, and amino acid metabolism and explore how reprogrammed metabolism provokes novel opportunities for biomarkers and potential therapeutic targets of ESCC.

Prognostic value of systemic inflammation score in patients with esophageal cancer.

Introduction: The systemic inflammatory score (SIS), a new inflammatory marker based on a combination of the lymphocyte-to-monocyte ratio (LMR) and serum albumin concentration, has been reported to be a useful prognostic marker for several malignancies. The authors conducted this retrospective study on data from a cohort of esophageal cancer patients undergoing potentially curative resection to clarify the value of SIS as a prognostic marker for clinical outcome in this population. Methods: This retrospective cohort study included 32 patients who underwent thoracoscopic esophagectomy after neoadjuvant chemotherapy for esophageal cancer between January 2016 and December 2019. Blood samples were collected within one week prior to the initiation of preoperative chemotherapy. Three inflammatory and nutritional markers; SIS, the neutrophil-to-lymphocyte ratio (NLR), and prognostic nutrition index (PNI) were examined in this study. Disease-free survival was assessed using the Kaplan-Meier method, and univariable and multivariable Cox models were applied to evaluate the predictive value of SIS, NLR and PNI. Results: NLR and PNI were not associated with recurrence, while SIS scores of 1 and 2 were significantly associated with recurrence. In multivariate analysis, SIS scores of 1 or 2 were found to be independently associated with recurrence, each with a hazard ratio of 1.98. In addition, when examining immunologic and nutritional factors and survival rates, there was no significant difference in the survival rate for NLR and PNI; for SIS, however, the survival rate was significantly worse in patients with SIS scores of 1 or 2. Conclusions: The authors demonstrated that a novel and easily obtained prognostic score, termed SIS, based on pre-treatment serum albumin and LMR, can serve as an independent prognostic factor in postoperative esophageal cancer patients. It could be incorporated into conventional clinical and pathological algorithms to enhance the prognostic accuracy in this population.

Risk of de novo esophageal cancer in liver transplant recipients: systematic review and meta-analysis.

Background: De novo malignancy is the leading cause of death in liver transplant recipients. Numerous studies consistently show a significantly increased risk of esophageal cancer after liver transplantation. Therefore, this study aims to investigate the incidence and risk factors associated with de novo esophageal cancer post-liver transplantation. Methods: PubMed, Embase, Medline and Cochrane Library were systematically searched. Screening, quality assessment, and data extraction were completed. The search was completed in November 2023. Standardized incidence rates (SIRs) were used to measure the risk of esophageal cancer among liver transplant recipients, along with corresponding 95% confidence intervals (CI). A random effects model was employed for comprehensive analysis, and results were presented using a forest plot. Sensitivity analysis was undertaken by systematically excluding individual studies one by one, while potential publication bias was assessed using funnel plots and Egger's test. Additionally, subgroup analyses were also performed to explore sources of heterogeneity. Results: Out of 1,037 articles collected, only twelve met the inclusion criteria after rigorous screening. Statistical analysis showed a significantly increased risk of esophageal cancer following liver transplantation compared to the general population (SIR =6.75, 95% CI: 4.35-10.46). Conclusions: The risk of esophageal cancer significantly increases after liver transplantation, so regular gastrointestinal endoscopy is necessary after the procedure.

Identification of a prognostic DNA repair gene signature in esophageal cancer.

Background: DNA repair plays a crucial role in the development and progression of different types of cancers. Nevertheless, little is known about the role of DNA repair-related genes (DRRGs) in esophageal cancer (EC). The present study aimed to identify a novel DRRGs prognostic signature in EC. Methods: Gene set enrichment analysis (GSEA) was performed to screen 150 genes related to DNA repair, which is the most important enrichment gene set in EC. Univariate and multivariate Cox regression analyses were used to screen DRRGs closely associated with prognosis. The difference in the expression of hub DRRGs between tumor and normal tissues was analyzed. Combined with clinical indicators (including age, gender, and tumor stage), we evaluated whether the 4-DRRGs signature was an independent prognostic factor. In addition, we evaluated the prediction accuracy using a receiver operating characteristic (ROC) curve and visualized the model's performance via a nomogram. Results: Four-DRRGs (NT5C3A, TAF9, BCAP31, and NUDT21) were selected by Cox regression analysis to establish a prognostic signature to effectively classify patients into high- and low-risk groups. The area under the curve (AUC) of the time-dependent ROC of the prognostic signature for 1- and 3-year was 0.769 and 0.720, respectively. Compared with other clinical characteristics, the risk score showed a robust ability to predict the prognosis in EC, especially in the early stage of EC. Furthermore, we constructed a nomogram to interpret the clinical application of the 4-DRRGs signature. Conclusions: In conclusion, we identified a prognostic signature based on the DRRGs for patients with EC, which can contribute independent value in identifying clinical outcomes that complement the TNM system in EC.

Association of Definitive Radiotherapy for Esophageal Cancer and the Incidence of Secondary Head and Neck Cancers: A SEER Population-Based Study.

Background: Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results: In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion: An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

A good response to anti-PD-1 monoclonal antibody plus SBRT in a patient with PD-L1-negative recurrent advanced esophageal cancer: a long-term follow-up case report of a possible abscopal effect.

There are limited treatment options for recurrent advanced esophageal squamous cell carcinoma. A good response with a possible abscopal effect was observed in a patient with programmed death-ligand 1 (PD-L1)-negative recurrent advanced esophageal squamous cell carcinoma treated with an anti-PD-1 monoclonal antibody plus stereotactic body radiotherapy (SBRT). A 66-year-old male patient was diagnosed with recurrent advanced esophageal squamous cell carcinoma with multiple lung metastases (13 metastatic nodules in total) four months after completing radical radiotherapy plus concurrent and consolidated chemotherapy, and PD-L1 expression in the primary esophageal tumor was negative. This patient received 25 cycles of camrelizumab (an anti-PD-1 monoclonal antibody) in total plus upfront SBRT for two metastatic nodules, which was administered after the first cycle of camrelizumab. After this combined treatment, for most nontarget nodules, an obvious volume decrease and fuzzy change were observed, including two nodules that completely vanished. At the end of follow-up, the progression-free survival and duration of response of this patient were 34 months and 32 months, respectively. This case report indicated that an anti-PD-1 monoclonal antibody combined with SBRT was a promising therapeutic strategy for recurrent esophageal squamous cell carcinoma even in patients with negative PD-L1 expression.

Anal metastasis in esophageal cancer: A case report.

BACKGROUND: Esophageal cancer is the sixth leading cause of cancer-related death and eighth most common cancer, affecting > 450000 people worldwide. Esophageal squamous cell carcinoma is the most common histological type, whereas esophageal adenoid cystic carcinoma (EACC) is rare. The liver is the most common distant metastatic site in esophageal cancer. Anal metastasis is rare and has not been reported in clinical practice before. Here, we report anal metastases in a patient with EACC after regular chemotherapy and surgical resection. CASE SUMMARY: A 61-year-old esophageal cancer patient was found to have lung and brain metastases during standardized treatment. The patient's treatment plan was continuously adjusted according to the latest treatment guidelines. However, the patient subsequently noticed rectal bleeding and itching, and after obtaining pathology results at the local hospital, anal metastasis of esophageal cancer was diagnosed. CONCLUSION: Postoperative pathology and immunohistochemistry confirmed EACC with rare anal metastasis. More exploration of EACC diagnosis and treatment is needed.

Circulating IgG Fragments for Gastric Cancer and Esophageal Cancer.

Blood serum of patients with gastric (n = 68) and esophageal (n = 43) cancer was assessed for proteolytic fragments of IgG. Serum samples of 20 healthy donors were used as a control. We analyzed indicators of hemostasis (prothrombin time, fibrinogen, plasminogen activity, a2-antiplasmin activity, protein C activity) in blood plasma and the level of total IgG in the blood serum. The median IgG-LysK of healthy donors was lower than in esophageal cancer and in patients with gastric cancer. ROC-analysis showed high sensitivity (91%) and specificity (85%) in the group with esophageal cancer but 68% and 85%, respectively, in patients with gastric cancer. Analysis of false negatives IgG-LysK in cancer patients showed that most patients had an advanced stage of cancer accompanied by metastases. Total IgG in the plasma of patients with false-negative IgG-LysK values was 30% lower than in samples with positive values, while the level of a2-antiplasmin was increased and the prothrombin time was shorter. These changes in blood homeostasis may be the reason for an increase in the proportion of false-negative values of the IgG-LysK coefficient. Circulatory IgG-LysK levels increase in the early stages of such cancers as gastric and esophageal cancers. Thus, when used in a panel with other more specific markers for these pathologies, this indicator can significantly increase the early detection of cancer.