Perioperative Outcomes and Survival of Modified Subxiphoid VATS Thymectomy for T2-3 Thymic Malignancies: A Retrospective Comparison Study.

OBJECTIVE: Our previous study demonstrated that modified subxiphoid VATS thymectomy (mSVT) with an auxiliary sternal retractor is feasible for locally invasive thymic malignancies. This study aimed to compare perioperative and oncological outcomes of mSVT versus median sternotomy thymectomy (MST) for locally advanced thymic malignancies. METHODS: In total, 221 patients of T2-3 thymic malignancies who underwent mSVT or MST between 2015 and 2020 were enrolled in our prospectively maintained database. A 1:1 propensity score-matching analysis was performed to balance the bias. Surgical difficulty was evaluated by a modified resection index. Perioperative and oncological results were compared between mSVT and MST groups. RESULTS: There were 72 patients in each group in the final analysis. Our results showed that the mSVT group had a shorter operative duration (98 vs. 129 min, P<0.001), less blood loss (40 vs.100 mL, P<0.001), shorter drainage duration (3 vs. 5 days, P<0.001), shorter length of hospital stay (5 vs. 6 days, P<0.001) and fewer postoperative complications (5.6% vs. 23.6%; P=0.005). No significant difference was detected in complete resection (98.6% vs. 98.6%, P =0.001) between the two groups. Conversion occurred in 5/106 (4.7%). Survival analyses indicated similar recurrence-free survival (HR=0.94; 95% CI: 0.40-2.20; p=0.883) and overall survival (HR=0.52; 95% CI: 0.05-5.02; p=0.590) between the two groups. CONCLUSION: The mSVT was safe and effective for T2-3 thymic malignancies and could be an alternative for selected patients with locally advanced thymic diseases. Further prospective studies are needed to evaluate the long-term survival of modified subxiphoid approach thoracoscopic thymectomy.

Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy for the treatment of thymic epithelial malignancies with pleural spread or recurrence (CHOICE): a study protocol for a prospective, open, single-arm study.

Background: Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (S-HITHOC) may be effective in treating thymic epithelial tumors (TETs) with pleural spread or recurrence. This study will evaluate the safety and efficacy of S-HITHOC in the treatment of TETs with pleural spread or recurrence. Methods: This study is an open, single-arm, prospective trial. Approximately 37 patients diagnosed with TETs with pleural spread or recurrence at the Zhongshan Hospital of Fudan University will be recruited and treated with S-HITHOC. The co-primary outcomes of the study are the length of postoperative hospital stay, complications, and overall quality of life (QoL). The secondary outcomes include drainage duration, volume, and cumulative pain scores. Discussion: This trial was approved by the Zhongshan Hospital Research Ethics Committee. The study findings will be actively disseminated through manuscript publications and conference presentations. Information sheets will be provided to each participant, and informed written consent will be obtained for each evaluation. This prospective study will evaluate the effectiveness of a surgical resection combined with the HITHOC procedure in treating TETs with pleural spread or recurrence in China and will support the standardization of the procedure. Registration: This trial was registered on Clinialtrial.gov (No. NCT05446935).

Efgartigimod is a new option for the treatment of thymoma associated myasthenia gravis: A case report.

INTRODUCTION: The perioperative efficacy and safety of efgartigimod in patients with thymoma associated myasthenia gravis have not been reported. CASE PRESENTATION: We described the case of a 47-year-old woman who presented thymoma associated myasthenia gravis. Primarily, the patient was treated with acetylcholinesterase inhibitors, immunosuppressive medications, and intravenous immunoglobulin. Unfortunately, the control of symptoms was unsatisfactory. The patient was treated with recommended dosage of efgartigimod (10 mg/kg administered as a 1 h intravenous infusion once weekly for 2 weeks) combined with immunosuppressive therapy. Consequently, improved outcomes and rapid clinical remission were observed. Then, modified subxiphoid thoracoscopic thymectomy was performed smoothly and the patient was discharged from hospital after recovery in short time. DISCUSSION: Administration of efgartigimod could control symptoms significantly and rapidly. Efgartigimod provides the opportunity of thymectomy in short time. Importantly, there was no any perioperative complication or any adverse event related to efgartigimod. CONCLUSION: The improved outcomes of the patient with thymoma associated myasthenia gravis highlight the importance of efgartigimod. Large-scale clinical trials are needed to validate the safety and efficacy of efgartigimod during the perioperative period of thymectomy.

WHO histological classification and tumor size are predictors of the locally aggressive behavior of thymic epithelial tumors.

OBJECTIVE: The aim of this study was to explore the influencing factors that affect the local invasive behavior of thymic epithelial tumors (TETs). METHOD: We retrospectively analyzed 524 patients with TETs who underwent surgical treatment at our center from January 2010 to January 2022. Cox regression analysis was applied to identify predictors associated with the prognosis of TET. Logistic regression analysis was used to analyze the factors associated with the locally invasive behavior of TETs. Receiver operating characteristic analysis and the Youden index were applied to determine the predictive efficiency and cutoff value. RESULTS: There were 275 males and 249 females with a median age of 56 years. Seventy-seven patients had locally invasive behavior. The prognosis of local invasive TETs was significantly worse that of noninvasive TETs (P < 0.001). WHO classification and tumor size were two hazard factors for tumor invasive behavior. The risk of local invasion increased by 2.196 (OR (95 % CI): 1.813-2.659) times for each grade in WHO classification with a change from type A to thymic carcinoma. The tumor size cutoff of 6 cm represented a distinct boundary in predicting the hazard of local invasion (AUC: 0.784, specificity: 0.711, sensitivity: 0.726). CONCLUSION: WHO classification and tumor size are important factors in predicting the locally aggressive behavior of TETs. The invasion capability of TETs is constantly increasing with an escalation in WHO classification. Tumors greater than 6 cm in size have a higher risk for local invasion.

Modified subxiphoid thoracoscopic thymectomy for early-stage thymic tumor: case report.

Background: Minimally invasive thymectomy via subxiphoid is increasingly being used for thymic tumors. Limited by the small space behind the sternum, the subxiphoid approach is sometimes difficult to perform. In this study, we introduce a modified subxiphoid thoracoscopic thymectomy which is performed via subxiphoid approach using an auxiliary sternal retractor to elevate the sternal to create a larger space behind the sternum. Therefore, the phrenic nerves on both sides were revealed more clearly and the left innominate vein was mobilized safer and easier. Case Description: This study describes the treatment process of a 27-year-old female patient with an incidental finding of a thymic mass. Chest contrast computed tomography revealed a 35 mm × 25 mm lesion in the anterior mediastinum which might be adherent to the left innominate vein. A careful preoperative evaluation was well done and no contraindications to the operation were found. This patient underwent modified subxiphoid thoracoscopic thymectomy, successfully completed without complications occurred during the perioperative period. The patient was discharged home well on post-operative day 2. The pathological diagnosis was mature teratoma. Conclusions: In conclusion, modified subxiphoid thoracoscopic thymectomy using an auxiliary sternal retractor makes minimally invasive thymectomy safer and simpler and is an alternative option for patients with early-stage thymic tumors.

ASCC3 promotes the immunosuppression and progression of non-small cell lung cancer by impairing the type I interferon response via CAND1-mediated ubiquitination inhibition of STAT3.

BACKGROUND: Activating signal cointegrator 3 (ASCC3) has been identified as an oncogenic factor that impairs host immune defense. However, the underlying mechanisms of carcinogenesis and its impact on the antitumor immune response remain unclear. In this study, we aimed to investigate the molecular mechanisms of ASCC3 in the progression of non-small cell lung cancer (NSCLC). METHODS: Single-cell sequencing data from the Gene Expression Omnibus and gene expression profiles from The Cancer Genome Atlas database were analyzed. The expression, clinical relevance and biological functions of ASCC3 in NSCLC were explored. Then, RNA sequencing, immunoprecipitation, mass spectrometry, immunofluorescence, and flow cytometry analyses were conducted to explore the underlying molecular mechanisms. In addition, in vivo experiments in mouse models were conducted to explore the probability of ASCC3 knockdown to improve the efficacy of anti-Programmed Death-1 (PD-1) therapy in NSCLC. RESULTS: ASCC3 was significantly upregulated in NSCLC and correlated with poor pathological characteristics and prognosis in patients with NSCLC. Overexpression of ASCC3 promoted malignant phenotypes of NSCLC cells and induced an immunosuppressive tumor microenvironment, which was characterized by a decrease in CD8+ T cells, natural killer cells and dendritic cells but an increase in regulatory T(Treg) cells. Mechanistically, ASCC3 stabilized signal transducer and activator of transcription (STAT)3 signaling by recruiting Cullin-associated and neddylation dissociated 1 (CAND1), which inhibited ubiquitin-mediated degradation of STAT3, thereby impairing the type I interferon response of tumor cells and promoting the immunosuppression and progression of NSCLC. Furthermore, high expression of ASCC3 impaired the efficacy of anti-PD-1 therapy, and an anti-PD-1 antibody combined with ASCC3 knockdown exerted promising synergistic efficacy in a preclinical mouse model. CONCLUSION: ASCC3 could stabilize the STAT3 pathway via CAND1, reshaping the tumor microenvironment and inducing resistance to anti-PD-1 therapy, which promotes the progression of NSCLC. It is a reliable prognostic indicator and can be a target in combination therapy for NSCLC.

Subxiphoid versus lateral intercostal thoracoscopic thymectomy for suspected thymoma: Results of a randomized controlled trial.

OBJECTIVE: This trial was to evaluate the efficacy of subxiphoid approach thoracoscopic thymectomy for postoperative pain control and length of hospital stay compared with a lateral intercostal approach thoracoscopic thymectomy. METHODS: This multicenter, open-label, randomized clinical superiority trial enrolled 101 eligible participants clinically diagnosed with Masaoka-Koga I-II thymoma between August 15, 2021, and February 15, 2022. Each enrolled participant was randomized and underwent subxiphoid approach thoracoscopic thymectomy or lateral intercostal approach thoracoscopic thymectomy. A per-protocol analysis for each coprimary outcome was performed in addition to the main intention-to-treat analysis. RESULTS: In the analysis for the coprimary outcomes, the pain Visual Analog Scale score area under the curve at 0 to 7 days was lower in the subxiphoid approach thoracoscopic thymectomy group than in the lateral intercostal approach thoracoscopic thymectomy group (difference, -4.82; 98.3% CI, -8.84 to -0.80). However, there was no significant difference between the 2 groups in the length of hospital stay (difference, 0.318; 98.3% CI, -0.190 to 0.825) or cumulative opioid consumption after surgery (difference, -4.630; 98.3% CI, -9.530 to 0.272). All patients underwent complete resection, and there was no significant difference (7.84% vs 8.00%, P = 1.000) in the rate of complications between the 2 groups. No recurrence or death occurred in the postoperative 6 months. CONCLUSIONS: This study found improved pain and similar length of hospital stay associated with the subxiphoid approach compared with the lateral intercostal approach in patients with suspected Masaoka-Koga I-II thymoma.

Comprehensive landscape and future perspective of long noncoding RNAs in non-small cell lung cancer: it takes a village.

Long noncoding RNAs (lncRNAs) are a distinct subtype of RNA that lack protein-coding capacity but exert significant influence on various cellular processes. In non-small cell lung cancer (NSCLC), dysregulated lncRNAs act as either oncogenes or tumor suppressors, contributing to tumorigenesis and tumor progression. LncRNAs directly modulate gene expression, act as competitive endogenous RNAs by interacting with microRNAs or proteins, and associate with RNA binding proteins. Moreover, lncRNAs can reshape the tumor immune microenvironment and influence cellular metabolism, cancer cell stemness, and angiogenesis by engaging various signaling pathways. Notably, lncRNAs have shown great potential as diagnostic or prognostic biomarkers in liquid biopsies and therapeutic strategies for NSCLC. This comprehensive review elucidates the significant roles and diverse mechanisms of lncRNAs in NSCLC. Furthermore, we provide insights into the clinical relevance, current research progress, limitations, innovative research approaches, and future perspectives for targeting lncRNAs in NSCLC. By summarizing the existing knowledge and advancements, we aim to enhance the understanding of the pivotal roles played by lncRNAs in NSCLC and stimulate further research in this field. Ultimately, unraveling the complex network of lncRNA-mediated regulatory mechanisms in NSCLC could potentially lead to the development of novel diagnostic tools and therapeutic strategies.

Detection of Epstein-Barr virus infection in thymic epithelial tumors by nested PCR and Epstein-Barr-encoded RNA ISH.

BACKGROUND: Epstein-Barr virus (EBV) is well known to be associated with a lot of tumors, including lymphoma, nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and some other carcinomas with similar lymphoepithelioma-like features. However, the association between EBV and thymic epithelial tumors (TETs) is inconclusive as reports in this regard are not entirely consistent and the methods employed are of different sensitivity and specificity. The geographical difference of the patients is also one of the reasons for the different points of view. METHODS: In our study, we examined 72 thymomas, including 3 cases of type A thymomas, 27 cases of type AB, 6 cases of type B1, 26 cases of type B2 and 10 cases of type B3 thymomas, and 15 thymic carcinomas to detect the viral genome at both DNA and RNA levels. The genome DNA of fresh tissues was first screened by nested polymerase chain reaction (PCR), which could be regarded as the most sensitive method to detect small amounts of DNA. Then all the tissue blocks were further submitted for viral localization by Epstein-Barr-encoded RNA (EBER) ISH. Group parameters were assessed using the chi-square test at a significance level of p < 0.05. RESULTS: Nested PCR results showed that none of type A, eight (29.6%) type AB, one (16.7%) type B1, fifteen (57.7%) type B2, and four (40.0%) type B3 were positive for EBV genome. However, none of them detected EBER expression except for one case of type B2 thymoma. Fourteen (93.3%) thymic carcinomas were positive for EBV by nested PCR, of which three displayed weak nuclear signals within the tumor cells by EBER ISH. CONCLUSIONS: These results showed that nested PCR was a sensitive method for screening the EBV genome in thymic epithelial tumors. As the malignancy of thymoma increases, the rate of EBV infection became higher. Thymic carcinomas were well associated with the Epstein-Barr virus.There was significant association between the EBV infection rate and thymoma type (p < 0.05). We further analyzed the association between EBV infection and myasthenia gravis. However, it showed no significant difference(p = 0.2754), although the EBV infection rate was higher in the thymomas with myasthenia gravis.

Prognostic Correlation between Tumor Volume and Complete Resection of Thymoma at Different Masaoka-Koga Stages.

OBJECTIVE: Thymoma is a slow-growing epithelial tumor of thymus gland. Its size is associated with its prognosis. The aim of this study was to analyze the prognostic correlation of tumor volume and complete resection of thymoma at different Masaoka-Koga stages. METHODS: A retrospective study was carried out, using the data of 502 patients who underwent complete resection of thymectomy at Zhongshan Hospital, Fudan University, in Shanghai, China, from February 2009 to February 2016. The characteristics of the patients were collected. Using Masaoka-Koga staging system, patients were divided into four different subcohorts: Stage I, stage II, stage III and stage IVa/IVb. The relationship between tumor volume and postoperative recurrence was analyzed for each subcohort, using receiver operating curves, cutoff values were obtained. and patients were grouped according to the cutoff values. Survival analysis was performed with the help of Kaplan-Meier method, and the difference between the two survival curves was compared using log-rank test. Whether tumor volume could be used as an independent risk factor for thymoma prognosis was analyzed, using a univariate Cox proportional hazards model. RESULTS: The area under the curve was 0.718, 0.740, 0.798, and 0.804 for the stage I, II, III, and IVa/IVb subcohorts, respectively, and the cutoff values of tumor volume for predicting recurrence were 47.90 cm3, 53.70 cm3, 76.35 cm3, and 89.05 cm3, respectively. Patients with tumor volumes greater than the cutoff values had significantly shorter recurrence-free survival than those with tumor volumes less than the cutoff values (p < 0.001). The results of the univariate Cox proportional hazards model indicated that tumor volume was an independent risk factor for thymoma prognosis and for postoperative prognosis of thymoma in Masaoka-Koga stage I (p < 0.001). CONCLUSIONS: Tumor volume is significantly correlated with the postoperative prognosis of thymoma in Masaoka-Koga stage I and can serve as an independent risk factor for predicting postoperative tumor recurrence.

Immunotherapy of thymic epithelial tumors: molecular understandings and clinical perspectives.

Immunotherapy has emerged to play a rapidly expanding role in the treatment of cancers. Currently, many clinical trials of therapeutic agents are on ongoing with majority of immune checkpoint inhibitors (ICIs) especially programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1, two main immune checkpoints, are expressed at high levels in thymic epithelial tumors (TETs) and could be predictors of the progression and immunotherapeutic efficacy of TETs. However, despite inspiring efficacy reported in clinical trials and clinical practice, significantly higher incidence of immune-related adverse events (irAEs) than other tumors bring challenges to the administration of ICIs in TETs. To develop safe and effective immunotherapeutic patterns in TETs, understanding the clinical properties of patients, the cellular and molecular mechanisms of immunotherapy and irAEs occurrence are crucial. In this review, the progress of both basic and clinical research on immune checkpoints in TETs, the evidence of therapeutic efficacy and irAEs based on PD-1 /PD-L1 inhibitors in TETs treatment are discussed. Additionally, we highlighted the possible mechanisms underlying irAEs, prevention and management strategies, the insufficiency of current research and some worthy research insights. High PD-1/PD-L1 expression in TETs provides a rationale for ICI use. Completed clinical trials have shown an encouraging efficacy of ICIs, despite the high rate of irAEs. A deeper mechanism understanding at molecular level how ICIs function in TETs and why irAEs occur will help maximize the immunotherapeutic efficacy while minimizing irAEs risks in TET treatment to improve patient prognosis.

Tumor-infiltrating CD36+CD8+T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer.

BACKGROUND: The scavenger receptor CD36 was reported to be highly expressed on tumor-infiltrating CD8+ T cells, but the clinical role remains obscure. This study aims to explore the infiltration and clinical value of CD36+CD8+ T cells in NSCLC. METHODS: Immunohistochemistry and immunofluorescence were conducted for survival analyses and immunological evaluation in 232 NSCLC patients in Zhongshan Hospital. Flow cytometry analyses were carried out to assess the immune cells from fresh tumor samples, non-tumor tissues and peripheral blood. In vitro tumor infiltrating lymphocytes cultures were conducted to test the effect of CD36 blockage. RESULTS: Accumulation of CD36+CD8+ T cells in tumor tissues was correlated with more advanced stage (p < 0.001), larger tumor size (p < 0.01), and lymph node metastasis (p < 0.0001) in NSCLC. Moreover, high infiltration of CD36+CD8+ T cells indicated poor prognosis in terms of both overall survival (OS) and recurrence-free survival (RFS) and inferior chemotherapy response. CD36+CD8+ T cells showed decreased GZMB (p < 0.0001) and IFN-γ (p < 0.001) with elevated PD-1 (p < 0.0001) and TIGIT (p < 0.0001). Analysis of tumor-infiltrating immune cell landscape revealed a positive correlation between CD36+CD8+ T cells and Tregs (p < 0.01) and M2-polarized macrophages (p < 0.01) but a negative correlation with Th1 (p < 0.05). Notably, inhibition of CD36 partially restored the cytotoxic function of CD8+ T cells by producing more GZMB and IFN-γ. CONCLUSION: CD36+CD8+ T cells exhibit impaired immune function and high infiltration of CD36+CD8+ T cells indicated poor prognosis and inferior chemotherapy response in NSCLC patients. CD36 could be a therapeutic target in combination with chemotherapy in NSCLC patients.

Comparison of the Perioperative Outcomes for Thoracoscopic Thymectomy Between the Subxiphoid Approach and the Lateral Intercostal Approach for Masaoka-Koga I-II Thymoma: A Propensity Score-Matching Analysis.

BACKGROUND: The appropriate approach for video-assisted thoracic surgery for early-stage thymoma remains debatable. The current study compared the safety and feasibility between subxiphoid-approach thoracoscopic thymectomy (SATT) and lateral intercostal-approach thoracoscopic thymectomy (LATT) for Masaoka-Koga stages 1 and 2 thymoma. METHODS: The study retrospectively enrolled 461 patients without myasthenia gravis who underwent SATT or LATT at the Zhongshan Hospital of Fudan University between 2016 and 2020. A 1:1 propensity score-matching (PSM) analysis was performed to control for selection bias. A series of perioperative outcomes, including surgical outcomes, inflammatory factors, morbidity and mortality, pain assessment, and quality of life, were compared. RESULTS: Each group consisted of 144 patients after PSM. The results showed that the SATT group had a significantly higher rate of exposure to the bilateral phrenic nerves (SATT [98.6 %] vs. LATT [77.1 %]; p < 0.001) as well as a larger maximum length (9.20 ± 3.08 vs. 7.52 ± 3.44 cm; p < 0.001) and width (6.13 ± 1.81 vs. 5.04 ± 1.77 cm; p < 0.001) of resected tissue than the LATT group. In addition, the SATT group had lower postoperative high-sensitivity C-reactive protein (hs-CRP) levels (9.37 ± 2.17 vs. 12.69 ± 2.13 mg/L; p < 0.001), better postoperative days 1, 3, and 7 visual analog pain scale (VAS) scores (p < 0.001), and better postoperative days 30 and 90 quality of life (p < 0.05). However, the two groups showed no significant increase in surgical time, estimated blood loss, total drainage time, postoperative total drainage volume, complications, or postoperative hospital stays. CONCLUSIONS: The study results suggest that the SATT is feasible and safe for Masaoka-Koga stages 1 and 2 thymoma.

Exosomal circZNF451 restrains anti-PD1 treatment in lung adenocarcinoma via polarizing macrophages by complexing with TRIM56 and FXR1.

BACKGROUND: Although success was achieved in the therapy for a minority of advanced lung adenocarcinoma (LUAD) patients, anti-programmed death 1 (PD1) resistance was found in most LUAD patients. Here, we aimed to uncover a potential role of exosomal circular RNAs (circRNAs) in LUAD refractory to PD1 blockade.  METHODS: circRNA sequencing and qRT-PCR were performed to determine the level of exosomal circRNAs in LUAD patients subsequently treated with anti-PD1. Then, the RNA pulldown, RNA immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, luciferase reporter assays, flow cytometry, RNA sequencing, and in vitro and in vivo models were used to uncover the biological functions and underlying mechanism of circZNF451 in LUAD anti-PD1 treatment resistance. RESULTS: circRNA sequencing and qRT-PCR identified the up-regulation of exosomal circZNF451 from LUAD patients with progressive disease (PD) compared to those with partial remission (PR) after PD1 blockade therapy. Furthermore, elevated circZNF451 was revealed to be associated with poor prognosis of LUAD patients. Additionally, exosomal circZNF451 was demonstrated to induce an anti-inflammatory phenotype in macrophages and exhaustion of cytotoxic CD8+ T cells, and enhanced TRIM56-mediated degradation of FXR1 to activate the ELF4-IRF4 pathway in macrophages. By transgenic mice, knockout of ELF4 in macrophages was found to rescue immunotherapy efficacy in tumors with high level of exosomal circZNF451. CONCLUSION: Exosomal circZNF451 reshapes the tumor immune microenvironment by inducing macrophages polarization via the FXR1- ELF4-IRF4 axis and is a novel biomarker for predicting the sensitivity of PD1 blockade in LUAD.

A novel predictive model for distinguishing mediastinal lymphomas from thymic epithelial tumours.

OBJECTIVES: We recently reported a high rate of nontherapeutic thymectomy. Mediastinal lymphomas (MLs) are the malignancies most likely to be confused with thymic epithelial tumours (TETs). This study aimed to establish a predictive model by evaluating clinical variables and positron emission tomography to distinguish those diseases. METHODS: From 2018 to 2021, consecutive patients who were pathologically diagnosed with TETs or MLs were retrospectively reviewed. Univariable and multivariable analyses were used to identify association factors. The Akaike information criterion was used to select variables. A nomogram was developed and validated to differentiate MLs from TETs. RESULTS: A total of 198 patients were included. Compared with TETs, patients with MLs were more likely to be younger with higher metabolic tumour volume (154.1 vs 74.6 cm3), total lesion glycolysis (1388.8 vs 315.2 g/ml cm3), SUVmean (9.2 vs 4.8), SUVpeak (12.9 vs 6.3) and SUVmax (14.8 vs 7.5). A nomogram was established based on the stepwise regression results and the final model containing age and SUVmax had minimal Akaike information criterion value of 72.28. Receiver operating characteristic analyses indicated that the area under the curve of predictive nomogram in differentiating MLs from TETs was 0.842 (95% CI: 0.754-0.907). The internal bootstrap resampling and calibration plots demonstrated good consistence between the prediction and the observation. CONCLUSIONS: Combination of age and SUVmax appears to be a useful tool to differentiate MLs from TETs. The novel predictive model prevents more patients from receiving nontherapeutic thymectomy.

Elevated circASCC3 limits antitumor immunity by sponging miR-432-5p to upregulate C5a in non-small cell lung cancer.

Although anti-programmed cell death 1 (PD1) treatment has become a first-line therapy for advanced non-small cell lung cancer (NSCLC), most NSCLC patients are refractory to anti-PD1. Here, we aimed to investigate the mechanism of dysregulated circular RNAs (circRNAs) related to anti-PD1 resistance in NSCLC. The expression of circASCC3 (hsa_circ_0077,495) in NSCLC tissues and cell lines was evaluated by fluorescence in situ hybridization and quantitative reverse transcription-polymerase chain reaction. The functions and mechanisms of circASCC3 in NSCLC progression and anti-PD1 resistance were uncovered in vitro and in vivo. The circASCC3 level was upregulated in NSCLC compared with that in paired normal tissues. Specifically, circASCC3 expression was higher in tissues from NSCLC patients with anti-PD1 refractory than in those from patients who sensitive to anti-PD1. Overexpression of circASCC3 enhanced the malignant phenotype of NSCLC cells and led to an immunosuppressive microenvironment. Mechanistically, circASCC3 sponged miR-432-5p to increase complement C5a levels, which enhanced the progression and dysfunctional immune status of NSCLC. Thus, circASCC3 overexpression reshapes the tumor microenvironment by impacting the complement system in NSCLC and provides a potential strategy to overcome anti-PD1 resistance.

How can the rate of nontherapeutic thymectomy be reduced?

OBJECTIVES: The aim of this study was to determine the prevalence of nontherapeutic thymectomy and define a clinical standard to reduce it. METHODS: From 2016 to 2020, consecutive patients who underwent thymectomy were retrospectively reviewed. Univariable and multivariable analyses were used to identify the correlation factors of nontherapeutic thymectomy. A receiver operating characteristic curve was analysed to assess the cut-off threshold of factors correlated with nontherapeutic thymectomy. RESULTS: A total of 1039 patients were included in this study. Overall, 78.4% (n = 814) of thymectomies were therapeutic and 21.6% (n = 225) were nontherapeutic. Thymoma (57.9%, n = 602) was the most common diagnosis in therapeutic thymectomy. Among those of nontherapeutic thymectomy, thymic cysts (11.9%, n = 124) were the most common lesion. Compared with therapeutic thymectomy, patients with nontherapeutic thymectomy were more likely to be younger (median age 50.1 vs 55.6 years, P < 0.001) with a smaller precontrast and postcontrast computed tomography (CT) value (P < 0.001, P < 0.001), as well as ΔCT value [10.7 vs 23.5 Hounsfield units (HU), P < 0.001]. Multivariable analysis indicated that only age and ΔCT value were significantly different between therapeutic and nontherapeutic thymectomy groups. Receiver operating characteristic curve analysis showed that cut-off values of age and ΔCT value were 44 years and 6 HU, respectively. Patients with age ≤44 years and a ΔCT value ≤6 HU had a 95% probability of nontherapeutic thymectomy. CONCLUSIONS: Surgeons should be cautious to perform thymectomy for patients with age ≤44 years and ΔCT value ≤6 HU. This simple clinical standard is helpful to reduce the rate of nontherapeutic thymectomy.

Recent thymic emigrants as the bridge between thymoma and autoimmune diseases.

Recent thymic emigrants (RTEs) are naïve T cells that egress the thymus following intrathymic development. This continuous process, including self-renewal, is crucial to establish and maintain human immune function. Several biomarkers can identify RTEs, but none of them is specific. Additional methods to detect and study RTEs phenotypically and functionally revealed alterations in RTEs in various adverse health conditions, including autoimmune diseases, systemic disorders and thymic abnormalities such as thymoma. Often associated with autoimmune disease, thymoma is the only tumor that can generate RTEs. However, a causal relationship between RTEs and autoimmune disease remains uncertain. Here, we review current knowledge about the connections between thymoma, RTEs and autoimmune diseases to provide new perspectives for therapeutic strategies.