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Background and objective: Esophageal cancer (EC) is the seventh most prevalent cancer globally and the sixth leading cause of cancer-related mortality. This study aimed to provide an updated stratified assessment of rates in EC incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 by sex, age, and Socio-demographic Index (SDI) at global, regional, and national levels, as well as to project the future trends of EC both globally and regionally. Methods: Data about age-standardized rates (ASRs) of incidence (ASIR), mortality (ASDR), probability of death (ASPoD) and DALYs (ASDALYRs) of EC were obtained from the 2021 Global Burden of Disease (GBD) study. Estimated annual percentage changes (EAPCs) and average annual percentage changes (AAPC) were calculated over certain periods to describe the temporal trends of EC burdens. The analyses were disaggregated by sexes, GBD super-regions and regions, nations/territories, age-groups, and SDI quintiles. A Bayesian age-period-cohort (BAPC) model was constructed to project the global and regional EC ASRs in 2022–2035. Results: Despite global reductions in EC ASRs, with ASIR, ASDR, and ASDALYR in 2021 of 6.65 [5.88, 7.45] (95% uncertainty interval), 6.25 [5.53, 7.00], and 148.56 [131.71, 166.82], decreasing by 24.9%, 30.7%, and 36.9% in 1990–2021, respectively, the absolute burden numbers were increased from 1990 to 2021, probably because of population growth and aging. Global newly diagnosed cases, deaths, and DALYs of EC increased to 576,529 [509,492, 645,648], 356,263 [319,363, 390,154], and 12,999,265 [11,522,861, 14,605,268] in 2021, by 62.53%, 51.18%, and 33.28% compared to records in 1990. The geographical pattern of EC was consistent: locations with the highest EC incidence and mortality rates were predominantly located in the Asian Esophageal Cancer Belt and African Esophageal Cancer Corridor, with East Asia, Southern Sub-Saharan Africa, and Eastern Sub-Saharan Africa as the GBD regions with the heaviest EC burdens, and Malawi, Eswatini, Mongolia, Zambia, and Zimbabwe with the most EC ASRs in 2021. However, owing to the population size, China, India, the United States, Japan, and Brazil had the heaviest absolute EC burdens. More pronounced alleviations of ASRs were observed in locations with high SDI levels, indicated by their lower AAPC values compared to those of low-SDI locations, while Sub-Saharan Africa regions had increasing EC ASRs, especially in Chad (114.76% in ASDR, for example), Sao Tome and Principe (97.93%), Togo (92.53%), Northern Mariana Islands (84.32%), Liberia (82.33%), etc. Smoking remained the leading contributor to EC ASDALYR globally and across most GBD super-regions in 2021. The EC burden is significantly heavier for males, with incidence and mortality in males in 2021 being 2.89 and 2.88 times higher, respectively, than in females. Across all age groups, EC posed an increasingly significant threat to men aged > 75 years. From 2022 to 2035, the ASR projections show only modest decrease in both global and regional EC burdens, and the absolute burden numbers are expected to increase globally and in nearly all GBD super-regions. Conclusion: EC burden remains significant, with disparities across sexes, age groups, and regions. Region-specific and age-targeted measures are crucial to addressing these inequalities, especially in light of increasing EC burdens in older men and in African regions. Efforts should be taken in finding more solid attributions to risk factors for EC burdens and to better identify high-risk populations to inform targeted prevention and screening, and ultimately reduce the EC burden in an efficient and cost-effective way. [ABSTRACT FROM AUTHOR]

As key oncogenic drivers in non-small-cell lung cancer (NSCLC), various mutations in the epidermal growth factor receptor (EGFR) with variable drug sensitivities have been a major obstacle for precision medicine. To achieve clinical-level drug recommendations, a platform for clinical patient case retrieval and reliable drug sensitivity prediction is highly expected. Therefore, we built a database, D3EGFRdb, with the clinicopathologic characteristics and drug responses of 1339 patients with EGFR mutations via literature mining. On the basis of D3EGFRdb, we developed a deep learning-based prediction model, D3EGFRAI, for drug sensitivity prediction of new EGFR mutation-driven NSCLC. Model validations of D3EGFRAI showed a prediction accuracy of 0.81 and 0.85 for patients from D3EGFRdb and our hospitals, respectively. Furthermore, mutation scanning of the crucial residues inside drug-binding pockets, which may occur in the future, was performed to explore their drug sensitivity changes. D3EGFR is the first platform to achieve clinical-level drug response prediction of all approved small molecule drugs for EGFR mutation-driven lung cancer and is freely accessible at https://www.d3pharma.com/D3EGFR/index.php. [ABSTRACT FROM AUTHOR]

Objectives: The performance of positron emission tomography/computed tomography (PET/CT) for the prediction of ypN2 disease in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy has not been reported. This multicenter study investigated the utility of PET/CT to assess ypN2 disease in these patients. Methods: A total of 181 consecutive patients (chemoimmunotherapy = 86, chemotherapy = 95) at four institutions were enrolled in this study. Every patient received a PET/CT scan prior to surgery and complete resection with systematic nodal dissection. The diagnostic performance was evaluated through area under the curve (AUC). Kaplan–Meier method and Cox analysis were performed to identify the risk factors affecting recurrences. Results: The sensitivity, specificity, and accuracy of PET/CT for ypN2 diseases were 0.667, 0.835, and 0.779, respectively. Therefore, the AUC was 0.751. Compared with the false positive cases, the mean value of max standardized uptake value (SUVmax) (6.024 vs. 2.672, p < 0.001) of N2 nodes was significantly higher in true positive patients. Moreover, the SUVmax of true positive (7.671 vs. 5.976, p = 0.365) and false (2.433 vs. 2.339, p = 0.990) positive cases were similar between chemoimmunotherapy and chemotherapy, respectively. Survival analysis proved that pathologic N (ypN) 2 patients could be stratified by PET/CT-N2(+ vs. -) for both chemoimmunotherapy (p = 0.023) and chemotherapy (p = 0.010). Conclusions: PET/CT is an accurate and non-invasive test for mediastinal restaging of NSCLC patients who receive neoadjuvant chemoimmunotherapy. The ypN2 patients with PET/CT-N2(+) are identified as an independent prognostic factor compared with PET/CT-N2(-). Clinical relevance statement: Imaging with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) plays an integral role during disease diagnosis, staging, and therapeutic response assessments in patients with NSCLC. PET/CT could be an effective non-invasive tool for predicting ypN2 diseases after neoadjuvant chemoimmunotherapy. Key Points: • PET/CT could serve as an effective non-invasive tool for predicting ypN2 diseases. • The ypN2 patients with PET/CT-N2(+) were a strong and independent prognostic factor. • The application of PET/CT for restaging should be encouraged in clinical practice. [ABSTRACT FROM AUTHOR]

Lung ischemia-reperfusion injury (IRI) stands as the primary culprit behind primary graft dysfunction (PGD) after lung transplantation, yet viable therapeutic options are lacking. In the present study, we used a murine hilar clamp (1 h) and reperfusion (3 h) model to study IRI. The left lung tissues were harvested for metabolomics, transcriptomics, and single-cell RNA sequencing. Metabolomics of plasma from human lung transplantation recipients was also performed. Lung histology, pulmonary function, pulmonary edema, and survival analysis were measured in mice. Integrative analysis of metabolomics and transcriptomics revealed a marked up-regulation of arachidonate 12-lipoxygenase (ALOX12) and its metabolite 12-hydroxyeicosatetraenoic acid (12-HETE), which played a pivotal role in promoting ferroptosis and neutrophil extracellular trap (NET) formation during lung IRI. Additionally, single-cell RNA sequencing revealed that ferroptosis predominantly occurred in pulmonary endothelial cells. Importantly, Alox12 -knockout (KO) mice exhibited a notable decrease in ferroptosis, NET formation, and tissue injury. To investigate the interplay between endothelial ferroptosis and NET formation, a hypoxia/reoxygenation (HR) cell model using 2 human endothelial cell lines was established. By incubating conditioned medium from HR cell model with neutrophils, we found that the liberation of high mobility group box 1 (HMGB1) from endothelial cells undergoing ferroptosis facilitated the formation of NETs by activating the TLR4/MYD88 pathway. Last, the administration of ML355, a targeted inhibitor of Alox12, mitigated lung IRI in both murine hilar clamp/reperfusion and rat left lung transplant models. Collectively, our study indicates ALOX12 as a promising therapeutic strategy for lung IRI., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Chongwu Li et al.)

Background: Although orthotopic single lung transplantation in rats has long been established, this model is still highly challenging. Therefore, we made several modifications in anesthesia, lung extraction, vascular clamp, and transplantation procedures for this model., Methods: Fifty cases of rat left lung transplantation were performed using traditional procedures and modified surgical techniques, respectively. Two hundred Sprague Dawley male rats, half as donors and half as recipients, were randomized equally to the two groups. The modifications included orotracheal intubation via a video laryngoscope, retrograde perfusion following anterograde perfusion, a Rummel tourniquet for the occlusion of pulmonary vessels, flushing the vessels and cuffs before anastomosis with heparin, and a simple pleural drainage. The surgical time, warm and cold ischemia time, vascular complications, and survival rate on postoperative day seven were compared between the two groups., Results: The modified surgical techniques significantly reduced the surgical duration (35.7 vs. 46.3 min, P<0.01), warm ischemia time (16.3 vs. 28.8 min, P<0.01), and vascular complications (2% vs. 16%, P=0.04). Moreover, the survival rate on postoperative day 7 was higher in the improved surgical techniques group (96% vs. 80%, P=0.03)., Conclusions: We described the improvement of surgical techniques for orthotopic single lung transplantation in rats, which could shorten anastomoses time, reduce vascular complications, and improve survival rate., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2018/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)