Combined model integrating deep learning, radiomics, and clinical data to classify lung nodules at chest CT.

OBJECTIVES: The study aimed to develop a combined model that integrates deep learning (DL), radiomics, and clinical data to classify lung nodules into benign or malignant categories, and to further classify lung nodules into different pathological subtypes and Lung Imaging Reporting and Data System (Lung-RADS) scores. MATERIALS AND METHODS: The proposed model was trained, validated, and tested using three datasets: one public dataset, the Lung Nodule Analysis 2016 (LUNA16) Grand challenge dataset (n = 1004), and two private datasets, the Lung Nodule Received Operation (LNOP) dataset (n = 1027) and the Lung Nodule in Health Examination (LNHE) dataset (n = 1525). The proposed model used a stacked ensemble model by employing a machine learning (ML) approach with an AutoGluon-Tabular classifier. The input variables were modified 3D convolutional neural network (CNN) features, radiomics features, and clinical features. Three classification tasks were performed: Task 1: Classification of lung nodules into benign or malignant in the LUNA16 dataset; Task 2: Classification of lung nodules into different pathological subtypes; and Task 3: Classification of Lung-RADS score. Classification performance was determined based on accuracy, recall, precision, and F1-score. Ten-fold cross-validation was applied to each task. RESULTS: The proposed model achieved high accuracy in classifying lung nodules into benign or malignant categories in LUNA 16 with an accuracy of 92.8%, as well as in classifying lung nodules into different pathological subtypes with an F1-score of 75.5% and Lung-RADS scores with an F1-score of 80.4%. CONCLUSION: Our proposed model provides an accurate classification of lung nodules based on the benign/malignant, different pathological subtypes, and Lung-RADS system.

Improving puncture accuracy in percutaneous CT-guided needle insertion with wireless inertial measurement unit: a phantom study.

OBJECTIVES: A novel method applying inertial measurement units (IMUs) was developed to assist CT-guided puncture, which enables real-time displays of planned and actual needle trajectories. The method was compared with freehand and laser protractor-assisted methods. METHODS: The phantom study was performed by three operators with 8, 2, and 0 years of experience in CT-guided procedure conducted five consecutive needle placements for three target groups using three methods (freehand, laser protractor-assisted, or IMU-assisted method). The endpoints included mediolateral angle error and caudocranial angle error of the first pass, the procedure time, the total number of needle passes, and the radiation dose. RESULTS: There was a significant difference in the number of needle passes (IMU 1.2 ± 0.42, laser protractor 2.9 ± 1.6, freehand 3.6 ± 2.0 time, p < 0.001), the procedure time (IMU 3.0 ± 1.2, laser protractor 6.4 ± 2.9, freehand 6.2 ± 3.1 min, p < 0.001), the mediolateral angle error of the first pass (IMU 1.4 ± 1.2, laser protractor 1.6 ± 1.3, freehand 3.7 ± 2.5 degree, p < 0.001), the caudocranial angle error of the first pass (IMU 1.2 ± 1.2, laser protractor 5.3 ± 4.7, freehand 3.9 ± 3.1 degree, p < 0.001), and the radiation dose (IMU 250.5 ± 74.1, laser protractor 484.6 ± 260.2, freehand 561.4 ± 339.8 mGy-cm, p < 0.001) among three CT-guided needle insertion methods. CONCLUSION: The wireless IMU improves the angle accuracy and speed of CT-guided needle punctures as compared with laser protractor guidance and freehand techniques. KEY POINTS: • The IMU-assisted method showed a significant decrease in the number of needle passes (IMU 1.2 ± 0.42, laser protractor 2.9 ± 1.6, freehand 3.6 ± 2.0 time, p < 0.001). • The IMU-assisted method showed a significant decrease in the procedure time (IMU 3.0 ± 1.2, laser protractor 6.4 ± 2.9, freehand 6.2 ± 3.1 min, p < 0.001). • The IMU-assisted method showed a significant decrease in the mediolateral angle error of the first pass and the caudocranial angle error of the first pass.

Estradiol-mediated inhibition of Sp1 decreases miR-3194-5p expression to enhance CD44 expression during lung cancer progression.

BACKGROUND: Sp1, an important transcription factor, is involved in the progression of various cancers. Our previous studies have indicated that Sp1 levels are increased in the early stage of lung cancer progression but decrease during the late stage, leading to poor prognosis. In addition, estrogen has been shown to be involved in lung cancer progression. According to previous studies, Sp1 can interact with the estrogen receptor (ER) to coregulate gene expression. The role of interaction between Sp1 and ER in lung cancer progression is still unknown and will be clarified in this study. METHODS: The clinical relevance between Sp1 levels and survival rates in young women with lung cancer was studied by immunohistochemistry. We validated the sex dependence of lung cancer progression in EGFRL858R-induced lung cancer mice. Wound healing assays, chamber assays and sphere formation assays in A549 cells, Taxol-induced drug-resistant A549 (A549-T24) and estradiol (E2)-treated A549 (E2-A549) cells were performed to investigate the roles of Taxol and E2 in lung cancer progression. Luciferase reporter assays, immunoblot and q-PCR were performed to evaluate the interaction between Sp1, microRNAs and CD44. Tail vein-injected xenograft experiments were performed to study lung metastasis. Samples obtained from lung cancer patients were used to study the mRNA level of CD44 by q-PCR and the protein levels of Sp1 and CD44 by immunoblot and immunohistochemistry. RESULTS: In this study, we found that Sp1 expression was decreased in premenopausal women with late-stage lung cancer, resulting in a poor prognosis. Tumor formation was more substantial in female EGFRL858R mice than in male mice and ovariectomized female mice, indicating that E2 might be involved in the poor prognosis of lung cancer. We herein report that Sp1 negatively regulates metastasis and cancer stemness in E2-A549 and A549-T24 cells. Furthermore, E2 increases the mRNA and protein levels of RING finger protein 4 (RNF4), which is the E3-ligase of Sp1, and thereby decreases Sp1 levels by promoting Sp1 degradation. Sp1 can be recruited to the promoter of miR-3194-5p, and positively regulate its expression. Furthermore, there was a strong inverse correlation between Sp1 and CD44 levels in clinical lung cancer specimens. Sp1 inhibited CD44 expression by increasing the expression of miR-3194-5p, miR-218-5p, miR-193-5p, miR-182-5p and miR-135-5p, ultimately resulting in lung cancer malignancy. CONCLUSION: Premenopausal women with lung cancer and decreased Sp1 levels have a poor prognosis. E2 increases RNF4 expression to repress Sp1 levels in premenopausal women with lung cancer, thus decreasing the expression of several miRNAs that can target CD44 and ultimately leading to cancer malignancy.

Algorithmic Approach Using Negative Pressure Wound Therapy Improved Survival for Patients with Synchronous Hypopharyngeal and Esophageal Cancer Undergoing Pharyngolaryngoesophagectomy with Gastric Tube Reconstruction.

BACKGROUND: This study retrospectively analyzed the feasibility and surgical outcome of an algorithmic approach using negative pressure wound therapy for patients with synchronous hypopharyngeal and esophageal cancer undergoing pharyngolaryngoesophagectomy with gastric tube reconstruction. METHODS: Patients undergoing pharyngolaryngoesophagectomy and gastric tube reconstruction for hypopharyngeal cancer between 2011 and 2019 were candidates for this study. Data were collected on patient demographics, comorbidities, performance status, cancer stage, treatment, complication, and survival. Survival analysis was performed using the Kaplan-Meier method. The Cox proportional hazards model was used for prognostic factors. RESULTS: The study enrolled 43 patients. Anastomotic leakage was found in 21 of the patients with a conventional surgical drain (61.9%) and in 10 of the 22 patients with negative pressure wound therapy (45.5%) (p = 0.280). Nine patients in the conventional drain group (42.9%) and two patients in the negative pressure wound therapy group (9.1%) had leakage-associated complications (p = 0.011). The incidence of pulmonary complications was higher in the conventional surgical drain group (9 vs 2; p = 0.011). The number of complications requiring surgery was higher in the conventional drain group (7 vs 0; p = 0.004). The overall survival in the negative pressure wound therapy group was better (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.15-0.76; p = 0.009). Negative pressure wound therapy was independently associated with overall survival (HR, 0.31; 95% CI, 0.13-0.77; p = 0.011). CONCLUSIONS: Negative pressure wound therapy with an algorithmic approach improved the overall survival for the patients undergoing gastric tube reconstruction after pharyngolaryngoesophagectomy for hypopharyngeal and esophageal cancer by preventing deadly complications secondary to anastomotic leakage.

Baseline plasma KL-6 level predicts adverse outcomes in patients with idiopathic pulmonary fibrosis receiving nintedanib: a retrospective real-world cohort study.

BACKGROUND: Nintedanib is effective for treating idiopathic pulmonary fibrosis (IPF), but some patients may exhibit a suboptimal response and develop on-treatment acute exacerbation (AE-IPF), hepatic injury, or mortality. It remains unclear which patients are at risk for these adverse outcomes. METHODS: We analysed the demographic and clinical data, baseline plasma levels of Krebs von den Lungen-6 (KL-6) and surfactant protein A (SPA), and longitudinal clinical courses of a real-world cohort of IPF patients who received nintedanib ≥ 14 days between March 2017 and December 2020. Cox proportional-hazards regression, subdistribution hazards regression, and sensitivity analyses were performed to investigate the association between baseline predictors and AE-IPF, mortality, and nintedanib-related hepatic injury. The relationship between baseline predictors and pulmonary function decline was determined. RESULTS: Fifty-seven patients were included, of whom 24 (42%) developed hepatic injury, 20 (35%) had AE-IPF, and 16 (28%) died on-treatment. A baseline plasma KL-6 level ≥ 2.5 ng/mL, and diffusion capacity for carbon monoxide (DLCO) < 55% predicted, were associated with increased risk of hepatic injury (adjusted hazard ratio [aHR] was 3.46; 95% CI 1.13-10.60; p = 0.029 for KL-6, and 6.05; 95% CI 1.89-19.32; p = 0.002 for DLCO). Both factors also predicted severe and recurrent hepatic injury. Patients with baseline KL-6 ≥ 2.5 ng/mL also had a higher risk of AE-IPF (aHR 4.52; 95% CI 1.63-12.55; p = 0.004). For on-treatment mortality, baseline KL-6 ≥ 3.5 ng/mL and SPA ≥ 600 pg/mL were significant predictors (aHR 5.39; 95% CI 1.16-24.97; p = 0.031 for KL-6, and aHR 12.28; 95% CI 2.06-73.05; p = 0.006 for SPA). Results from subdistribution hazard regression and sensitivity analyses supported these findings. Patients with elevated baseline plasma KL-6 levels also exhibited a trend towards faster pulmonary function decline. CONCLUSIONS: For patients with IPF who are receiving nintedanib, we have identified baseline predictors, in particular plasma KL-6 levels, for the risk of adverse outcomes. Patients with these predictors may require close monitoring for unfavourable responses during treatment. Our findings also support the prognostic role of molecular markers like KL-6 and may contribute to future formulation of more individualized therapeutic strategies for IPF.

Single-port thoracoscopic anatomic resection for chronic inflammatory lung disease.

BACKGROUND: It is challenging to proceed thoracoscopic anatomic resection when encountering severe pleural adhesion or calcified peribronchial lymphadenopathy. Compared with multiple-port video-assisted thoracoscopic surgery (MP-VATS), how to overcome these challenges in single-port (SP-) VATS is still an intractable problem. In the present study, we reported the surgical results of chronic inflammatory lung disease and shared some useful SP-VATS techniques. METHODS: We retrospectively assessed the surgical results of chronic inflammatory lung disease, primarily bronchiectasis, and mycobacterial infection, at our institution between 2010 and 2018. The patients who underwent SP-VATS anatomic resection were compared with those who underwent MP-VATS procedures. We analyzed the baseline characteristics, perioperative data, and postoperative outcomes, and illustrated four special techniques depending on the situation: flexible hook electrocautery, hilum-first technique, application of Satinsky vascular clamp, and staged closure of bronchial stump method. RESULTS: We classified 170 consecutive patients undergoing thoracoscopic anatomic resection into SP and MP groups, which had significant between-group differences in operation time and overall complication rate (P = 0.037 and 0.018, respectively). Compared to the MP-VATS group, the operation time of SP-VATS was shorter, and the conversion rate of SP-VATS was relatively lower (3.1% vs. 10.5%, P = 0.135). The most common complication was prolonged air leakage (SP-VATS, 10.8%; MP-VATS, 2.9%, P = 0.045). CONCLUSIONS: For chronic inflammatory lung disease, certain surgical techniques render SP-VATS anatomic resection feasible and safe with a lower conversion rate.

EGFR-TKI plus bevacizumab versus EGFR-TKI monotherapy for patients with EGFR mutation-positive advanced non-small cell lung cancer-A propensity score matching analysis.

BACKGROUND: Recent study showed that the combination of erlotinib and bevacizumab had better disease control than erlotinib monotherapy in patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). However, there is lack of real-world evidence for this therapeutic regimen. We aimed to compare outcomes between patients with EGFR mutant NSCLC treated with EGFR-tyrosine kinase inhibitors (TKI) and bevacizumab and those treated with EGFR-TKI alone in a real-world setting. METHODS: Patients with advanced EGFR-mutant NSCLC who received first-line EGFR-TKI in a tertiary referral center from October 1, 2013 to December 31, 2019 were retrospectively analyzed. We performed 1:2 propensity score-matching: one EGFR-TKI and bevacizumab recipient with two patients who received EGFR-TKI alone. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. The prognostic factors were analyzed using Cox proportional hazards regression analysis. RESULTS: Total 313 patients were enrolled. After propensity score matching, 45 patients who received first-line EGFR-TKI and bevacizumab and 89 patients who received EGFR-TKI alone were analyzed. The combination group showed improved PFS (17.0 vs. 11.0 months; hazard ratio [HR] = 0.48; p = 0.002) compared to the monotherapy group. In subgroup analysis of patients with an L858R mutation, the combination group showed longer PFS (23.1 vs. 10.7 months; HR = 0.40; p = 0.011) and OS (not reached vs. 40.6 months; HR = 0.27; p = 0.040) than the EGFR-TKI monotherapy group. CONCLUSION: Our data suggest that the combination of EGFR-TKI and bevacizumab could improve PFS in patients with EGFR-mutant NSCLC. In patients harboring L858R mutation, the combination therapy provides better OS than TKI alone.

Esophageal reconstruction after oncological total laryngopharyngoesophagectomy: Algorithmic approach.

BACKGROUND: Reconstruction for total laryngopharyngoesophagectomy is accomplished mainly by gastrointestinal transposition but can be complicated by anastomotic tension or associated neck-skin defect. Here, we present the results of total esophageal reconstruction by gastrointestinal transposition alone or with additional free tissue transfer and propose an algorithm accordingly. METHODS: We reviewed patients who had oncologic total laryngopharyngoesophagectomy between January 2012 and January 2016. Twenty-four men and one woman were included with a mean age of 54 (range, 41-72) years. Patients were grouped by reconstruction into the gastric pull-up (GP, n = 15), colon interposition (CI, n = 2), GP combined with free jejunal flap (GPFJ, n = 6), or GP combined with anterolateral thigh flap (GPALT, n = 2) group to compare clinical outcomes. RESULTS: The mean operation time was 1037.3 minutes and was significantly longer in the GPALT group than in the GP group (1235.0 ± 50.0 minutes vs. 929.7 ± 137.7 minutes, p =.009). All flaps survived. After a mean follow-up of 18 months, the overall leakage, stricture, and successful swallowing rates were 44%, 4%, and 76%, respectively. There was no significant difference in the leakage (53.3%, 50.0%, 16.7%, and 50.0%, p =.581), stricture (6.7%, 0%, 0%, and 0%, p = 1.000), or successful swallowing (73.3%, 50.0%, 83.3%, and 100%, p =.783) rates between GP, CI, GPFJ, and GPALT groups, respectively. CONCLUSIONS: The proposed algorithm that ranks gastric pull-up as a priority and uses additional free tissue transfer to overcome the anastomotic tension or associated neck-skin defect is feasible.

Over-expression of prothymosin-α antagonizes TGFß signalling to promote the development of emphysema.

Emphysema, a major consequence of chronic obstructive pulmonary disease (COPD), is characterized by the permanent airflow restriction resulting from enlargement of alveolar airspace and loss of lung elasticity. Transforming growth factor-ß (TGFß) signalling regulates the balance of matrix metalloproteinase (MMP)/tissue inhibitor of matrix metalloproteinase (TIMP) to control matrix homeostasis. Patients with COPD have dysregulated TGFß signalling and reduced histone deacetylase (HDAC) activity through epigenetic up-regulation of histone acetylation in the promoters of pro-inflammatory genes. However, the potential link between decreased HDAC activity and dysregulated TGFß signalling in emphysema pathogenesis remains to be determined. Prothymosin α (ProT), a highly conserved acidic nuclear protein, plays a role in the acetylation of histone and non-histone proteins. The aim of this study was to test the hypothesis that ProT inhibits TGFß-Smad signalling through Smad7, thereby contributing to emphysema pathogenesis. We show that ProT enhances Smad7 acetylation by decreasing its association with HDAC and thereby down-regulates TGFß-Smad signalling. ProT caused an imbalance between MMP and TIMP through acetylated Smad7 in favour of MMP expression. In addition to interfering with R-Smad activation and targeting receptors for degradation in the cytoplasm, acetylated Smad7 potentiated by ProT competitively antagonized binding of the pSmad2/3-Smad4 complex to the TIMP-3 promoter, resulting in reduced TIMP-3 expression. These effects were detected in ProT-over-expressing cells, lungs of ProT transgenic mice displaying an emphysema phenotype and in emphysema patients. Importantly, increased Smad7 and reduced TIMP-3 were found in the lungs of emphysema patients and mice with cigarette smoke extract (CSE)-induced emphysema. Such effects could be abrogated by silencing endogenous ProT expression. Collectively, our results uncover acetylated Smad7 regulated by ProT as an important determinant in dysregulated TGFß signalling that contributes to emphysema pathogenesis.

hRAD9 functions as a tumor suppressor by inducing p21-dependent senescence and suppressing epithelial-mesenchymal transition through inhibition of Slug transcription.

Senescence and epithelial-mesenchymal transition (EMT) have opposing roles in tumor progression, in that, one is a barrier against tumorigenesis, whereas the other is required for invasive malignancies. Here, we report that the DNA damage response (DDR) protein hRAD9 contributes to induction of senescence and inhibition of EMT. Our data show that hRAD9 is frequently downregulated in breast and lung cancers. Loss of hRAD9 expression is associated with tumor stage in breast and lung cancers, as well as with acquisition of an invasive phenotype. Ectopic hRAD9 expression in highly invasive cancer cell lines, H1299 and MDA-MB 231, with low endogenous hRAD9 induced senescence by upregulation of nuclear p21, independent of the p53 status. Ectopic expression of hRAD9 also significantly attenuated cellular migration and invasion in vitro and tumor growth in a xenograft mouse model in vivo. In contrast, silencing hRAD9 in lower invasive cancer cell lines, A549 and MCF7, with high endogenous hRAD9 dramatically increased their migration and invasion abilities, and simultaneously activated EMT. Knockdown of hRAD9 increased, whereas ectopic expression of hRAD9 decreased, the expression of Slug. Moreover, hRAD9 directly bound to the promoter region of slug gene and repressed its transcriptional activity. Taken together, these results suggest that hRAD9 is a potential tumor suppressor in breast and lung cancers and that it is likely to function by upregulating p21 and inhibiting Slug to regulate tumorigenesis.

A scenario-based web app to facilitate patient education in lung tumor patients undergoing video-assisted thoracoscopic surgery: Development and usability testing.

Background: Patient education (PE) is essential for improving patients' knowledge, anxiety, and satisfaction, and supporting their postoperative recovery. However, the advantages of video-assisted thoracoscopic surgery (VATS)-smaller incisions and faster recovery-can result in shorter hospital stays, making PE more challenging to implement effectively. Multimedia PE can potentially enhance PE, but its effectiveness for patients undergoing VATS is unclear. Objective: This study developed a scenario-based PE web app for lung tumor patients undergoing VATS (SPE-VATS) to facilitate the PE process and evaluated its usability through a clinical trial. Methods: The SPE-VATS provided the experimental group (EG: 32 participants) with interactive scenario, query guidance, diagnostic analysis, experience sharing, and active reminder, while the control group (CG: 32 participants) used pamphlets and videos. The usability of SPE-VATS in terms of postoperative anxiety reduction and patient satisfaction with the app was evaluated using self-reported questionnaires based on the state-trait anxiety inventory, technology acceptance model, system usability scale, and task load index. Results: There was no statistically significant difference in postoperative anxiety reduction between the EG and CG, possibly because 90% of the participants underwent a low-risk surgical type, and VATS is known to be advantageous in alleviating surgical anxiety. However, females and higher educated EG participants showed a non-significant but favorable reduction than their CG counterparts. Moreover, the EG was highly satisfied with the app (rated 4.2 to 4.4 out of 5.0), with no significant gender and education level difference. They particularly valued the interactive scenario, experience sharing, and diagnostic analysis features of SPE-VATS. Conclusions: The SPE-VATS demonstrated its usability and high patient satisfaction, particularly for female and higher educated patients. Low-risk patient predominance and VATS's advantages may explain non-significant postoperative anxiety reduction, warranting further studies on high-risk patients to evaluate the impact of SPE-VATS on clinical practice.

IL-33/NF-κB/ST2L/Rab37 positive-feedback loop promotes M2 macrophage to limit chemotherapeutic efficacy in lung cancer.

IL-33 is a danger signal that binds to its receptor ST2L to promote tumor progression. This study identifies the IL-33/ST2L positive-feedback loop and the trafficking of ST2L membrane presentation in macrophages that contribute to lung tumor progression. Mechanistically, IL-33 induces ST2L upregulation by activating NF-κB, which binds to the promoter region of the ST2L gene. Moreover, Rab37, a small GTPase involved in membrane trafficking, mediates ST2L trafficking to the plasma membrane of M2 macrophages. This IL-33/NF-κB/ST2L/Rab37 axis promotes positive-feedback loops that enhance ST2L expression and membrane trafficking in M2 macrophages. Notably, neutralizing antibodies against IL-33 or ST2L block NF-κB activity, suppress M2 macrophage polarization, and synergistically inhibit tumor growth when combined with cisplatin treatment in vitro/vivo. Clinically, Rab37+/ST2L+/CD206+ tumor-infiltrating M2 macrophages correlate with advanced-stage lung cancer patients with poor response to chemotherapy. These findings unveil a positive-feedback mechanism and provide a basis for IL-33/ST2L-targeting therapy for cancer.

Development of a real-time RGB-D visual feedback-assisted pulmonary rehabilitation system.

Background: Following surgery, perioperative pulmonary rehabilitation (PR) is important for patients with early-stage lung cancer. However, current inpatient programs are often limited in time and space, and outpatient settings have access barriers. Therefore, we aimed to develop a background-free, zero-contact thoracoabdominal movement-tracking model that is easily set up and incorporated into a pre-existing PR program or extended to home-based rehabilitation and remote monitoring. We validated its effectiveness in providing preclinical real-time RGB-D (colour-depth camera) visual feedback. Methods: Twelve healthy volunteers performed deep breathing exercises following audio instruction for three cycles, followed by audio instruction and real-time visual feedback for another three cycles. In the visual feedback system, we used a RealSense™ D415 camera to capture RGB and depth images for human pose-estimation with Google MediaPipe. Target-tracking regions were defined based on the relative position of detected joints. The processed depth information of the tracking regions was visualised on a screen as a motion bar to provide real-time visual feedback of breathing intensity. Pulmonary function was simultaneously recorded using spirometric measurements, and changes in pulmonary volume were derived from respiratory airflow signals. Results: Our movement-tracking model showed a very strong correlation (r = 0.90 ± 0.05) between thoracic motion signals and spirometric volume, and a strong correlation (r = 0.73 ± 0.22) between abdominal signals and spirometric volume. Displacement of the chest wall was enhanced by RGB-D visual feedback (23 vs 20 mm, P = 0.034), and accompanied by an increased lung volume (2.58 vs 2.30 L, P = 0.003). Conclusion: We developed an easily implemented thoracoabdominal movement-tracking model and reported the positive impact of real-time RGB-D visual feedback on self-promoted external chest wall expansion, accompanied by increased internal lung volumes. This system can be extended to home-based PR.

Robot-assisted surgery outperforms video-assisted thoracoscopic surgery for anterior mediastinal disease: a multi-institutional study.

Anterior mediastinal procedures are increasingly being performed using robot-assisted thoracic surgery (RATS) or video-assisted thoracoscopic surgery (VATS). While both approaches have shown superior outcomes compared to open surgery, their comparative benefits are not as distinct. The aim of this retrospective study was to bridge this knowledge gap using a multicenter dataset. Patients who underwent elective minimally invasive surgery for anterior mediastinal disease between 2015 and 2022 were deemed eligible. The study participants were grouped based on whether a robot was used or not, and perioperative outcomes were compared. To mitigate selection bias, inverse probability of treatment weighting (ITPW) was applied using the propensity score. The final analysis included 312 patients (RATS = 120; VATS = 192). Following the application of IPTW, RATS was found to be associated with a longer operating time (215.3 versus 139.31 min, P < 0.001), fewer days with a chest tube (1.96 versus 2.61 days, P = 0.047), and a shorter hospital stay (3.03 versus 3.91 days, P = 0.041) compared to VATS. Subgroup analyses indicated that the benefit of RATS in reducing the length of hospital stay was particularly pronounced in patients with tumors larger than 6 cm (mean difference [MD] = - 2.28 days, P = 0.033), those diagnosed with myasthenia gravis (MD = - 3.84 days, P = 0.002), and those who underwent a trans-subxiphoid surgical approach (MD = - 0.81 days, P = 0.04). Both VATS and RATS are safe and effective approaches for treating anterior mediastinal disease. However, RATS holds distinct advantages over VATS including shorter hospital stays and reduced chest tube drainage periods.

Baseline Blood Levels of Mucin-1 Are Associated with Crucial On-Treatment Adverse Outcomes in Patients with Idiopathic Pulmonary Fibrosis Receiving Antifibrotic Pirfenidone.

Mucin-1 is a multi-functional glycoprotein expressed by type II alveolocytes and may be detectable in the circulation following pulmonary fibrosis. The prognostic utility of baseline pre-treatment blood levels of mucin-1 in patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotics has not yet been fully established. We retrospectively studied a cohort of patients (from two hospitals) with IPF who were receiving pirfenidone for >12 weeks. Baseline blood mucin-1 levels were measured via sandwich enzyme-linked immunosorbent assays. We investigated the performance of mucin-1 levels in longitudinally predicting the risks of acute exacerbation of IPF (AE-IPF) and severe adverse outcomes (SAO), including lung transplantation and death. Seventy patients were included; 20 developed AE-IPF; and 31 had SAO during the follow-up period. Patients with baseline mucin-1 levels ≥2.5 ng/mL had enhanced risks of AE-IPF (adjusted hazard ratio [aHR], 14.07; 95% confidence interval [CI], 4.26-46.49) and SAO within 2 years (aHR, 7.87; 95% CI, 2.86-21.70) and anytime during the follow-up (aHR, 4.68; 95% CI, 2.11-10.39). The risks increased across subgroups with increasing mucin-1 levels. Patients in the "mucin-1 ≥ 2.5" group also exhibited an accelerated decline in DLCO. This study supports baseline blood mucin-1 levels as a biomarker for IPF that predicts adverse outcomes during pirfenidone treatment.

Lymph node volume predicts survival in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery.

Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.

USP24-i-101 targeting of USP24 activates autophagy to inhibit drug resistance acquired during cancer therapy.

Drug resistance in cancer therapy is the major reason for poor prognosis. Addressing this clinically unmet issue is important and urgent. In this study, we found that targeting USP24 by the specific USP24 inhibitors, USP24-i and its analogues, dramatically activated autophagy in the interphase and mitotic periods of lung cancer cells by inhibiting E2F4 and TRAF6, respectively. USP24 functional knockout, USP24C1695A, or targeting USP24 by USP24-i-101 inhibited drug resistance and activated autophagy in gefitinib-induced drug-resistant mice with doxycycline-induced EGFRL858R lung cancer, but this effect was abolished after inhibition of autophagy, indicating that targeting USP24-mediated induction of autophagy is required for inhibition of drug resistance. Genomic instability and PD-L1 levels were increased in drug resistant lung cancer cells and were inhibited by USP24-i-101 treatment or knockdown of USP24. In addition, inhibition of autophagy by bafilomycin-A1 significantly abolished the effect of USP24-i-101 on maintaining genomic integrity, decreasing PD-L1 and inhibiting drug resistance acquired in chemotherapy or targeted therapy. In summary, an increase in the expression of USP24 in cancer cells is beneficial for the induction of drug resistance and targeting USP24 by USP24-i-101 optimized from USP24-i inhibits drug resistance acquired during cancer therapy by increasing PD-L1 protein degradation and genomic stability in an autophagy induction-dependent manner.

Therapeutic Decision Making in Prevascular Mediastinal Tumors Using CT Radiomics and Clinical Features: Upfront Surgery or Pretreatment Needle Biopsy?

The study aimed to develop machine learning (ML) classification models for differentiating patients who needed direct surgery from patients who needed core needle biopsy among patients with prevascular mediastinal tumor (PMT). Patients with PMT who received a contrast-enhanced computed tomography (CECT) scan and initial management for PMT between January 2010 and December 2020 were included in this retrospective study. Fourteen ML algorithms were used to construct candidate classification models via the voting ensemble approach, based on preoperative clinical data and radiomic features extracted from the CECT. The classification accuracy of clinical diagnosis was 86.1%. The first ensemble learning model was built by randomly choosing seven ML models from a set of fourteen ML models and had a classification accuracy of 88.0% (95% CI = 85.8 to 90.3%). The second ensemble learning model was the combination of five ML models, including NeuralNetFastAI, NeuralNetTorch, RandomForest with Entropy, RandomForest with Gini, and XGBoost, and had a classification accuracy of 90.4% (95% CI = 87.9 to 93.0%), which significantly outperformed clinical diagnosis (p < 0.05). Due to the superior performance, the voting ensemble learning clinical-radiomic classification model may be used as a clinical decision support system to facilitate the selection of the initial management of PMT.

Development of a modified 3D region proposal network for lung nodule detection in computed tomography scans: a secondary analysis of lung nodule datasets.

BACKGROUND: Low-dose computed tomography (LDCT) has been shown useful in early lung cancer detection. This study aimed to develop a novel deep learning model for detecting pulmonary nodules on chest LDCT images. METHODS: In this secondary analysis, three lung nodule datasets, including Lung Nodule Analysis 2016 (LUNA16), Lung Nodule Received Operation (LNOP), and Lung Nodule in Health Examination (LNHE), were used to train and test deep learning models. The 3D region proposal network (RPN) was modified via a series of pruning experiments for better predictive performance. The performance of each modified deep leaning model was evaluated based on sensitivity and competition performance metric (CPM). Furthermore, the performance of the modified 3D RPN trained on three datasets was evaluated by 10-fold cross validation. Temporal validation was conducted to assess the reliability of the modified 3D RPN for detecting lung nodules. RESULTS: The results of pruning experiments indicated that the modified 3D RPN composed of the Cross Stage Partial Network (CSPNet) approach to Residual Network (ResNet) Xt (CSP-ResNeXt) module, feature pyramid network (FPN), nearest anchor method, and post-processing masking, had the optimal predictive performance with a CPM of 92.2%. The modified 3D RPN trained on the LUNA16 dataset had the highest CPM (90.1%), followed by the LNOP dataset (CPM: 74.1%) and the LNHE dataset (CPM: 70.2%). When the modified 3D RPN trained and tested on the same datasets, the sensitivities were 94.6%, 84.8%, and 79.7% for LUNA16, LNOP, and LNHE, respectively. The temporal validation analysis revealed that the modified 3D RPN tested on LNOP test set achieved a CPM of 71.6% and a sensitivity of 85.7%, and the modified 3D RPN tested on LNHE test set had a CPM of 71.7% and a sensitivity of 83.5%. CONCLUSION: A modified 3D RPN for detecting lung nodules on LDCT scans was designed and validated, which may serve as a computer-aided diagnosis system to facilitate lung nodule detection and lung cancer diagnosis.

A modified 3D RPN for detecting lung nodules on CT images that exhibited greater sensitivity and CPM than did several previously reported CAD detection models was established.