Site-specific delivery of cisplatin and paclitaxel mediated by liposomes: A promising approach in cancer chemotherapy.

The site-specific delivery of drugs, especially anti-cancer drugs has been an interesting field for researchers and the reason is low accumulation of cytotoxic drugs in cancer cells. Although combination cancer therapy has been beneficial in providing cancer drug sensitivity, targeted delivery of drugs appears to be more efficient. One of the safe, biocompatible and efficient nano-scale delivery systems in anti-cancer drug delivery is liposomes. Their particle size is small and they have other properties such as adjustable physico-chemical properties, ease of functionalization and high entrapment efficiency. Cisplatin is a chemotherapy drug with clinical approval in patients, but its accumulation in cancer cells is low due to lack of targeted delivery and repeated administration results in resistance development. Gene and drug co-administration along with cisplatin/paclitaxel have resulted in increased sensitivity in tumor cells, but there is still space for more progress in cancer therapy. The delivery of cisplatin/paclitaxel by liposomes increases accumulation of drug in tumor cells and impairs activity of efflux pumps in promoting cytotoxicity. Moreover, phototherapy along with cisplatin/paclitaxel delivery can increase potential in tumor suppression. Smart nanoparticles including pH-sensitive nanoparticles provide site-specific delivery of cisplatin/paclitaxel. The functionalization of liposomes can be performed by ligands to increase targetability towards tumor cells in mediating site-specific delivery of cisplatin/paclitaxel. Finally, liposomes can mediate co-delivery of cisplatin/paclitaxel with drugs or genes in potentiating tumor suppression. Since drug resistance has caused therapy failure in cancer patients, and cisplatin/paclitaxel are among popular chemotherapy drugs, delivery of these drugs mediates targeted suppression of cancers and prevents development of drug resistance. Because of biocompatibility and safety of liposomes, they are currently used in clinical trials for treatment of cancer patients. In future, the optimal dose of using liposomes and optimal concentration of loading cisplatin/paclitaxel on liposomal nanocarriers in clinical trials should be determined.

The effect of metformin on senescence of T lymphocytes.

BACKGROUND: Immunosenescence occurs as people age, leading to an increased incidence of age-related diseases. The number of senescent T cells also rises with age. T cell senescence and immune response dysfunction can result in a decline in immune function, especially in anti-tumor immune responses. Metformin has been shown to have various beneficial effects on health, such as lowering blood sugar levels, reducing the risk of cancer development, and slowing down the aging process. However, the immunomodulatory effects of metformin on senescent T cells still need to be investigated. METHODS: PBMCs isolation from different age population (n = 88); Flow Cytometry is applied to determine the phenotypic characterization of senescent T lymphocytes; intracellular staining is applied to determine the function of senescent T cells; Enzyme-Linked Immunosorbent Assay (ELISA) is employed to test the telomerase concentration. The RNA-seq analysis of gene expression associated with T cell senescence. RESULTS: The middle-aged group had the highest proportion of senescent T cells. We found that metformin could decrease the number of CD8 + senescent T cells. Metformin affects the secretion of SASP, inhibiting the secretion of IFN-γ in CD8 + senescent T cells. Furthermore, metformin treatment restrained the production of the proinflammatory cytokine IL-6 in lymphocytes. Metformin had minimal effects on Granzyme B secretion in senescent T cells, but it promoted the production of TNF-α in senescent T cells. Additionally, metformin increased the concentration of telomerase and the frequency of undifferentiated T cells. The results of RNA-seq showed that metformin promoted the expression of genes related to stemness and telomerase activity, while inhibiting the expression of DNA damage-associated genes. CONCLUSION: Our findings reveal that metformin could inhibit T cell senescence in terms of cell number, effector function, telomerase content and gene expression in middle-aged individuals, which may serve as a promising approach for preventing age-related diseases in this population.

Lymphatic Node Metastasis Risk Scoring System: A Novel Instrument for Predicting Lymph Node Metastasis After Thymic Epithelial Tumor Resection.

BACKGROUND: The authors aimed to create a novel model to predict lymphatic metastasis in thymic epithelial tumors. METHODS: Data of 1018 patients were collected from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. To construct a nomogram, the least absolute shrinkage and selection operator (LASSO) regression model was used to select candidate features of the training cohort from 2004 to 2013. A simple model called the Lymphatic Node Metastasis Risk Scoring System (LNMRS) was constructed to predict lymphatic metastasis. Using patients from 2014 to 2015 as the validation cohort, the predictive performance of the model was determined by receiver operating characteristic (ROC) curves. RESULTS: The LASSO regression model showed that age, extension, and histology type were significantly associated with lymph node metastasis, which were used to construct the nomogram. Through analysis of the area under the curve (AUC), the nomogram achieved a AUC value of 0.80 (95 % confidence interval [Cl] 0.75-0.85) in the training cohort and 0.82 (95 % Cl 0.70-0.93) in the validation cohort, and had closed calibration curves. Based on the nomogram, the authors constructed the LNMRS model, which had an AUC of 0.80 (95 % Cl 0.75-0.85) in the training cohort and 0.82 (95% Cl 0.70-0.93) in the validation cohort. The ROC curves indicated that the LNMRS had excellent predictive performance for lymph node metastasis. CONCLUSION: This study established a nomogram for predicting lymph node metastasis. The LNMRS model, constructed to predict lymphatic involvement of patients, was more convenient than the nomogram.

Photocatalytic inactivation of algae in a fluidized bed photoreactor with an external magnetic field.

Practical applications of photocatalysis in algae removal often involve the use of photoreactors, which can be of many different configurations. In this study, a fluidized bed photoreactor (FBPR) with an external magnetic field was designed and constructed to achieve algae inactivation continuously and stably. Magnetic photocatalyst ZnFe2O4/Ag3PO4/g-C3N4 attached to Fe3O4 aggregate, was dispersed and fixed at the bottom of the reactor to form a flower-like structure, which can not only increase the effective irradiation area of the photocatalyst, but also enhances mass transfer by inducing flow disturbance. Under the optimal operating conditions, i.e., 0.04 m/s flow rate, 200 mT magnetic field strength, and 0.025 g photocatalyst loading, the photoreactor can effectively remove algae cells within 6 h. During the continuous operation experiment, the quality of the magnetic photocatalyst and aggregate did not decrease significantly, and there was still a 90% removal efficiency after 18 h of continuous operation. Furthermore, in the experiment where humic acid was added to simulate actual water environment, certain advantages can still be observed with the FBPR. As a continuous reactor using a magnetic photocatalyst, the FBPR has the characteristics of high availability, low cost, and low energy consumption.

A Modified VATS Procedure for Treating Adult Intralobar Pulmonary Sequestration.

Video-assisted thoracoscopic surgery (VATS) makes it possible to treat intralobar sequestration (ILS) more minimally invasive compared with conventional open surgery. However, this procedure is challenging to expose and isolate the aberrant arteries of ILS and the risk of bleeding is high. Herein, we developed a modified VATS procedure in which the aberrant vessels are treated in the last step of lobectomy, rather than at the beginning. In this way, we can expose the aberrant vessels easier and reduce the risk of massive blood loss, also simplifying the surgical procedure.

Relationship of possible biomarkers with malignancy of thymic tumors: a meta-analysis.

BACKGROUND: Role of biomarkers for promotion of tumor proliferation (BPTPs) and for promotion of apoptosis (BPAs) in thymic malignant tumors is still unclear. The purpose of this study was to evaluate the relationship between BPTPs and/or BPAs and malignancy of thymic malignant tumors. METHODS: Studies on thymic malignant tumors and biomarkers were searched in PubMed, ISI Web of Knowledge, and Embase databases, and all statistical analyses were conducted using Review Manager. RESULTS: Twelve articles related to biomarkers and thymic malignant tumors were selected and analyzed. A relationship between BPAs and Masaoka stage was demonstrated for four markers, namely Bax, p73, Casp-9 and Bcl-2, included 138 stage I/II patients and 74 stage III/IV patients, and BPAs were significantly correlated with high Masaoka staging (P = 0.03). We further found a relationship between BPAs and degree of malignancy for four markers, namely Bax, p73, Casp-9 and Bcl-2, included 176 thymoma patients and 36 thymic carcinoma patients, and BPAs were significantly correlated with thymic carcinoma (P = 0.010). In addition, a relationship between BPTP and Masaoka staging was demonstrated for seven markers, namely Podoplanin, Glut-1, Muc-1, Egfr, Igf1r, c-Jun, and n-Ras, included 373 patients with stage I/II and 212 patients with stage III/IV, and BPTPs were significantly correlated with high Masaoka staging (P < 0.001). We also found a relationship between BPTPs and degree of malignancy for ten markers, namely Mesothelin, c-Kit (CD117), Egfr, Lat-1, Muc-1,Ema, Glut-1, Igf1r, c-Jun, and n-Ras, included 748 thymoma patients and 280 thymic carcinoma patients, and BPTPs were significantly correlated with thymic carcinoma (P < 0.001). CONCLUSION: These findings show that high levels of BPTPs or BPAs are more closely related to thymic carcinoma and Masaoka stage III/IV, suggesting that BPTPs and BPAs may play an important role in the occurrence and development of thymic malignant tumors.

Expression of fibronectin in esophageal squamous cell carcinoma and its role in migration.

BACKGROUND: Fibronectin (FN) is a high-molecular-weight glycoprotein component of the extracellular matrix involved in cell adhesion, migration, metastasis, proliferation and differentiation, as well as embryogenesis, wound healing, and blood coagulation. Considerable recent research has established that tumor expression of FN is closely associated with tumor formation and development as well as disease prognosis. However, the mechanisms underlying this relationship have remained unclear. The aim of this study was to investigate FN protein expression in esophageal squamous cell carcinoma (ESCC) and determine its potential prognostic relevance, while also elucidating the source and function of FN. METHODS: We conducted immunohistochemical analyses of protein expression in primary tumors of ESCC patients and analyzed their association with standard prognostic parameters and clinical outcomes. Expression of FN in two ESCC cell lines (Eca-109 and TE-1) was also examined by RT-PCR, immunofluorescence, and ELISA. ESCC cells were cultured in a microenvironment containing a high FN content, and changes in their morphology and migration ability were assessed by microscopy, wound-healing assays, and Transwell assays. RESULTS: FN expression in ESCC specimens was mainly detected in the tumor stroma, with very little FN detected in tumor cells. Stromal FN content in ESCC specimens was associated with lymphatic metastasis (P = 0.032) and prognosis. In this latter context, patients with high tumor stromal expression of FN showed worse overall survival (P = 0.002) and progression-free survival (P < 0.001) than those with low expression of FN. Interestingly, FN expression and secretion in ESCC cell lines (Eca-109 and TE-1) was found to be low, but these cells adopted a more migratory phenotype when cultured in vitro in a microenvironment containing high levels of FN. CONCLUSIONS: High FN expression in the stroma of ESCC tumors is closely associated with poor prognosis of patients. High stromal FN content facilitates tumor cell metastasis by promoting morphological changes and improving the motility and migratory ability of ESCC cells.

Effect of Prophylactic Thoracic Duct Ligation in Reducing the Incidence of Postoperative Chylothorax during Esophagectomy: A Systematic Review and Meta-analysis.

OBJECTIVES: There is no consensus on the effectiveness of prophylactic thoracic duct ligation (PLG) in esophagectomy for reducing the incidence of postoperative chylothorax. We performed a systemic review and meta-analysis to study its efficacy. METHODS: A systemic review of the publications was performed on three databases to identify all the relevant literature on comparative outcomes of PLG and nonprophylactic thoracic duct ligation (NPLG). The primary end point was the incidence of postoperative chylothorax. RESULTS: Seven studies with comparative data on PLG (n = 2,178) versus NPLG (n = 3,048) were identify from the current publications. Comparison showed no significant difference between PLG and NPLG on the incidence of postoperative chylothorax (relative risk = 0.431; 95% confidence interval, 0.186 to 1.002; p = 0.050). CONCLUSIONS: Although some studies showed that PLG during the esophagectomy was effective to lower the incidence of postoperative chylothorax, no evidence was observed in the present meta-analysis. Further research is warranted to validate the findings.

Long Non-Coding RNA Prostate Cancer-Associated Transcript 7 (PCAT7) Induces Poor Prognosis and Promotes Tumorigenesis by Inhibiting mir-134-5p in Non-Small-Cell Lung (NSCLC).

BACKGROUND Long non-coding RNA PCAT7 has been revealed to participate in tumorigenesis of various cancers. However, the mechanism of PCAT7 in non-small cell lung cancer (NSCLC) has not been identified. Hence, this study aimed to determine the function of PCAT7 in NSCLC. MATERIAL AND METHODS The expression level of PCAT7 in 96 pairs of NSCLC tissues and 6 cell lines was detected by qRT-PCR. Proliferation assay, flow cytometric analysis, transwell/migration assay, and Western blotting assay were performed to detect the relation between PCAT7 and malignant behaviors of NSCLC cells in vitro, including cell proliferation, apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT). Rescue assays were carried out to confirm the contribution of PCAT7 to the progression of NSCLC cells by targeting miR-134-5p. RESULTS PCAT7 was found to be overexpressed in NSCLC tissues (compared with corresponding non-tumor tissues) and NSCLC cells (compared with normal cell line 16-HBE). Overexpression of PCAT7 resulted in the promotion of tumor cell proliferation, inhibition of cells apoptosis, facilitation of cells metastasis, and formation of EMT phenotype, while PCAT7 expression deletion remarkably prohibited cell proliferation, accelerated their apoptosis, weakened metastasis, and reversed EMT to MET. miR-134-5P, as a target gene of PCAT7, restored the effects of down-regulation of PCAT7. CONCLUSIONS These findings demonstrate that PCAT7 participates in tumor progression in NSCLC by inhibiting miR-134-5p.

Clinical Outcomes of Thymectomy in Myasthenia Gravis Patients with a History of Crisis.

BACKGROUND: The use of thymectomy in myasthenia gravis (MG) patients with a history of myasthenic crisis (MC) has not been well established. Here, we determined the efficacy of thymectomy by assessing the long-term clinical outcomes and reviewed thymectomy reports on MC patients. METHODS: Subjects included 31 patients who suffered at least one crisis before surgery, with a cumulative total 73 episodes of MC in Southern China between May 2000 and December 2010. Long-term follow-up was performed and clinical outcomes were evaluated. We used complete stable remission (CSR), termed an asymptomatic status without medication for at least 12 months; general complete remission (GCR), termed an asymptomatic status with or without some form of therapy excluding cholinesterase inhibitors, to assess patient outcomes. RESULTS: All patients underwent thymectomy with an overall complication rate of 16.1 % and a perioperative mortality rate of 3.2 %. Long-term follow-up occurred between 12.6 and 177 months, at which point 18 (58.1 %) patients experienced improved status, including one patient who achieved CSR; 13 (41.9 %) patients achieved GCR; 6 (19.4 %) showed unchanged status and one worse (3.2 %) status. The remaining 6 patients died, with 3 due to MG-related causes. Using a multivariate Cox regression analysis of GCR by characteristics, patients with better response to medical treatments before thymectomy were positively associated with GCR rates (p = 0.028). CONCLUSIONS: Extended transsternal thymectomy is a feasible and effective therapy for MG patients with crisis history, especially for those patients who have shown positive signs of remission after exhausting conventional medical treatments.

Airway epithelial cell-derived insulin-like growth factor-1 triggers skewed CD8(+) T cell polarization.

Skewed CD8(+) T cell responses are important in airway inflammation. This study investigates the role of the airway epithelial cell-derived insulin-like growth factor 1 (IGF1) in contributing to CD8(+) T cell polarization. Expression of IGF1 in the airway epithelial cell line, RPMI2650 cells, was assessed by quantitative real time RT-PCR and Western blotting. The role of IGF1 in regulating CD8(+) T cell activation was observed by coculture of mite allergen-primed RPMI2650 cells and naïve CD8(+) T cells. CD8(+) T cell polarization was assessed by the carboxyfluorescein succinimidyl ester-dilution assay and the determination of cytotoxic cytokine levels in the culture medium. Exposure to mite allergen, Der p1, increased the expression of IGF1 by RPMI2650 cells. The epithelial cell-derived IGF1 prevented the activation-induced cell death by inducing the p53 gene hypermethylation. Mite allergen-primed RPMI2650 cells induced an antigen-specific CD8(+) T cell polarization. We conclude that mite allergens induce airway epithelial cell line, RPMI2650 cells, to produce IGF1; the latter contributes to antigen-specific CD8(+) T cell polarization.

Aurora-A is a novel predictor of poor prognosis in patients with resected lung adenocarcinoma.

BACKGROUND: The Aurora-A (Aur-A) gene, a key regulator of mitosis, has been proved as an oncogene in a variety of cancers. The Aur-A overexpression has been proved correlated with aggressiveness of cancer cells. However, the frequency of Aur-A protein overexpression, as well as its association with clinicopathologic parameters and prognosis remain unclear in lung adenocarcinoma (ADC). This study tried to clarify the clinical significance of Aur-A in patients with resected lung ADC. PATIENTS AND METHODS: A total of 142 informative patients with surgically resected lung ADC and 20 normal lung tissues were enrolled. Western blot and immunohistochemistry (IHC) were utilized to assess protein expression of Aur-A. RESULT: The expression of Aur-A was elevated in most of tumor tissues compared with the adjacent tissues by western blot. The IHC results showed that Aur-A protein was over-expressed in 98 of 142 (69.0%) tumor sections, while Aur-A was low-expressed in all normal lung sections. A positive correlation between Aur-A overexpression rate and ascending pathologic stages was observed (P<0.05). Kaplan-Meier analysis demonstrated that patients with Aur-A high expression had significantly inferior survival compared to those with Aur-A low expression. Both overall survival (OS) and disease-free survival (DFS) of positive overexpression patients were shorter than the negative group (P=0.036, P=0.041, respectively). Multivariate analysis confirmed that Aur-A expression, as an independent and significant factor for both DFS and OS, could predict a poor prognosis in patients with resected lung ADC (P=0.022, P=0.049, respectively). CONCLUSIONS: Aur-A was overexpressed in lung ADC and overexpression of Aur-A might be a novel predictor for poor prognosis and potential therapeutic target in lung ADC.

Autophagy-driven regulation of cisplatin response in human cancers: Exploring molecular and cell death dynamics.

Despite the challenges posed by drug resistance and side effects, chemotherapy remains a pivotal strategy in cancer treatment. A key issue in this context is macroautophagy (commonly known as autophagy), a dysregulated cell death mechanism often observed during chemotherapy. Autophagy plays a cytoprotective role by maintaining cellular homeostasis and recycling organelles, and emerging evidence points to its significant role in promoting cancer progression. Cisplatin, a DNA-intercalating agent known for inducing cell death and cell cycle arrest, often encounters resistance in chemotherapy treatments. Recent studies have shown that autophagy can contribute to cisplatin resistance or insensitivity in tumor cells through various mechanisms. This resistance can be mediated by protective autophagy, which suppresses apoptosis. Additionally, autophagy-related changes in tumor cell metastasis, particularly the induction of Epithelial-Mesenchymal Transition (EMT), can also lead to cisplatin resistance. Nevertheless, pharmacological strategies targeting the regulation of autophagy and apoptosis offer promising avenues to enhance cisplatin sensitivity in cancer therapy. Notably, numerous non-coding RNAs have been identified as regulators of autophagy in the context of cisplatin chemotherapy. Thus, therapeutic targeting of autophagy or its associated pathways holds potential for restoring cisplatin sensitivity, highlighting an important direction for future clinical research.

Role of mitochondrial metabolism in immune checkpoint inhibitors-related myocarditis.

Background: Immune checkpoint inhibitor-related myocarditis is the deadliest complication of immunotherapy. However, the underlying pathophysiological mechanisms of its occurrence and development remain unclear. Due to the long-term lack of effective early diagnosis and treatment options, it is of great significance to understand the pathophysiological mechanism of immune checkpoint inhibitor-related myocarditis. Methods: Tissue samples from three patients with immune checkpoint inhibitor-related myocarditis and three control tissue samples were collected for protein analysis. Differentially expressed proteins were screened out using quantitative proteomics technology based on TMT markers. Protein-protein interaction (PPI) and Gene Ontology (GO) functional enrichment analyses of cross-factors were subsequently performed. Combined with the PD-L1 subcellular organelle- level protein interaction network, we searched for hub proteins involved in immune checkpoint inhibitor-related myocarditis and explored potential drug sensitivity and disease correlation. Results: A total of 306 differentially expressed proteins were identified in immune checkpoint inhibitor-related myocarditis. Enrichment analysis showed that the differentially expressed proteins were closely related to mitochondrial metabolism. By analyzing mitochondria-related proteins and PD-L1-related proteins, we found four hub proteins, mammalian target of rapamycin (mTOR), Glycogen synthase kinase 3ß (GSK3ß), Protein tyrosine phosphatase non-receptor type 11 (PTPN11), and Mitofusin 2 (MFN2), indicating that they are closely related to immune checkpoint inhibitor-related myocarditis. Finally, we explored potential drugs for the treatment of immune checkpoint inhibitor-related myocarditis. Conclusion: Mitochondrial metabolism is involved in the process of immune checkpoint inhibitor-related myocarditis, and we identified four hub proteins, which may become new biomarkers for the early diagnosis and treatment of immune checkpoint inhibitor-related myocarditis.

Role of glycosphingolipid biosynthesis coregulators in malignant progression of thymoma.

As the most common malignancy from mediastinum, the metabolic reprogramming of thymoma is important in its development. Nevertheless, the connection between the metabolic map and thymoma development is yet to be discovered. Thymoma was categorized into three subcategories by unsupervised clustering of molecular markers for metabolic pathway presentation in the TCGA dataset. Different genes and functions enriched were demonstrated through the utilization of metabolic Gene Ontology (GO) analysis. To identify the main contributors in the development of thymic malignancy, we utilized Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The prognosis of thymoma was evaluated by screening the essential pathways and genes using GSVA scores and machine learning classifiers. Furthermore, we integrated the transcriptomics findings with spectrum metabolomics investigation, detected through LC-MS/MS, in order to establish the essential controller network of metabolic reprogramming during thymoma progression. The thymoma prognosis is related to glycosphingolipid biosynthesis-lacto and neolacto series pathway, of what high B3GNT5 indicate poor survival. The investigation revealed that glycosphingolipid charts have a significant impact on metabolic dysfunction and could potentially serve as crucial targets in the clinical advancement of metabolic therapy.

Methylation of N6 adenosine-related long noncoding RNA: effects on prognosis and treatment in 'driver-gene-negative' lung adenocarcinoma.

The improvement of treatment for patients with 'driver-gene-negative' lung adenocarcinoma (LUAD) remains a critical problem to be solved. We aimed to explore the role of methylation of N6 adenosine (m6A)-related long noncoding RNA (lncRNA) in stratifying 'driver-gene-negative' LUAD risk. Patients negative for mutations in EGFR, KRAS, BRAF, HER2, MET, ALK, RET, and ROS1 were identified as 'driver-gene-negative' cases. RNA sequencing was performed in 46 paired tumors and adjacent normal tissues from patients with 'driver-gene-negative' LUAD. Twenty-three m6A regulators and relevant lncRNAs were identified using Pearson's correlation analysis. K-means cluster analysis was used to stratify patients, and a prognostic nomogram was developed. The CIBERSORT and pRRophetic algorithms were employed to quantify the immune microenvironment and chemosensitivity. We identified two clusters highly consistent with the prognosis based on their unique expression profiles for 46 m6AlncRNAs. A risk model constructed from nine m6A lncRNAs could stratify patients into high- and low-risk groups with promising predictive power (C-index = 0.824), and the risk score was an independent prognostic factor. The clusters and risk models were closely related to immune characteristics and chemosensitivity. Additional pan-cancer analysis using the nine m6AlncRNAs showed that the expression of DIO3 opposite strand upstream RNA (DIO3OS) is closely related to the immune/stromal score and tumor stemness in a variety of cancers. Our results show that m6AlncRNAs are a reliable prognostic tool and can aid treatment decision-making in 'driver-gene-negative' LUAD. DIO3OS is associated with the development of various cancers and has potential clinical applications.

Efficiency of ectopic thymectomy by three surgical approaches in non-thymomatous myasthenia gravis.

BACKGROUND: To explore the efficiency of ectopic thymectomy by the three surgical approaches of trans-sternum, right unilateral thoracoscopy and thoracoscopic subxiphoid in patients with non-thymomatous myasthenia gravis. METHODS: 155 consecutive non-thymomatous myasthenia gravis patients who underwent extended thymectomy by 3 approaches including trans-sternum, right unilateral thoracoscopy and thoracoscopic subxiphoid in 1st affiliated hospital of Sun Yat-Sen University from January 2017 to October 2019 were reviewed. Differences of perioperative clinical characteristics in three surgical approaches were analyzed. RESULTS: Time to onset of myasthenia gravis (early or late) (p = 0.018), blood loss (p < 0.001), duration of operation (p = 0.031), duration and volume of thoracic drainage (p = 0.039 and p = 0.026), length of hospitalization (p = 0.039), the efficiency of ectopic thymectomy (p = 0.037), and the detection rate of ectopic thymus in the second quadrant (p = 0.018) were different among the three surgical approaches. In univariate logistic regression analysis, higher efficiency of ectopic thymectomy were associated with transsternal (OR 2.36, 95% CI 1.32-4.22, p = 0.011) and thoracoscopic subxiphoid approaches (OR 2.07, 95% CI 1.12-3.82, p = 0.033). In the multiple logistic regression analysis, the transsternal approach (OR 2.02, 95% CI 1.10-3.71, p = 0.024) was an independent protective factor for the efficiency of ectopic thymectomy. CONCLUSIONS: Both the right unilateral thoracoscopic and thoracoscopic subxiphoid approaches have advantages over the transsternal approach in short-term postoperative recovery. Transsternal approach is still the best choice for ectopic thymectomy while thoracoscopic subxiphoid approach show the potential as an alternative way.

Expression of Programmed Cell Death 1 Ligand 2 in Patients With Thymoma and Thymomatous Myasthenia Gravis.

OBJECTIVES: This study aimed to examine the expression of programmed cell death 1 ligand 2 (PD-L2) in thymoma and thymomatous myasthenia gravis (MG). METHODS: The records of 70 patients with thymoma receiving surgical resection between January 2017 and December 2018 were retrospectively reviewed. Thymoma PD-L2 expression was evaluated by immunohistochemistry staining. Associations between PD-L2 expression and clinicopathologic features were examined. RESULTS: PD-L2 expression was positive in 41 patients (58.6%) and negative in 29 patients (41.4%). Of them, 33 had thymomatous MG. Patients with MG were more likely to be 50 years of age or younger (69.70% vs 35.14%); have more World Health Organization (WHO) type B thymomas (84.85% vs 64.86%); have tumors of smaller size (4.09 ± 2.33 cm vs 6.47 ± 2.42 cm); have positive PD-L2 expression (78.79% vs 40.54%); and have a higher percentage of PD-L2-positive cells, higher PD-L2 expression intensity, and score (all P < .05). Positive PD-L2 expression was associated with more type B thymomas, higher Masaoka-Koga stage, smaller tumor size, ectopic thymus, and MG (all P < .05). Factors significantly associated with MG were age under 50 years, tumor size less than 5 cm, and positive PD-L2 expression (all P < .05). CONCLUSIONS: Thymoma PD-L2 expression is significantly associated with thymomatous MG and WHO histologic types B2 and B3.

Neurological outcomes of extended thymectomy for thymomatous myasthenia gravis: Subxiphoid vs. trans-sternal approaches.

Background: The subxiphoid approach has been widely used recently. However, there is little data focusing on neurological outcomes in patients with thymomatous myasthenia gravis (MG) who underwent subxiphoid thoracoscopic thymectomy. The purpose of this study was to compare the neurological outcomes of patients with thymomatous MG who underwent extended thymectomy with a subxiphoid or transthoracic approach 1 year postoperatively. Methods: The records of patients with Masaoka stage I and II thymomas who underwent extended thymectomy from January 2019 to December 2020 with tumor size less than 5 cm and thymomatous MG were retrospectively reviewed and evaluated. Neurological outcomes were measured by a quantitative myasthenia gravis score (QMGS), with a 2.3-point reduction in QMGS associated with improvement in clinical MG status. The clinical efficacy and variables affecting the outcomes were assessed using the Kaplan-Meier method and Cox proportional hazard regression analysis. Results: A total of 89 patients were included in the analysis, of which 44 had a subxiphoid approach and 45 had a trans-sternal approach. Mean QMGS decreased from 12 at initial diagnosis to 8.7 preoperatively and 5.6 at 12 months postoperatively in the subxiphoid group and from 12.1 to 8.9 to 6.0 in the transthoracic group. Thirteen patients (28.9%) who underwent the trans-sternal approach and 10 (22.7%) who underwent the subxiphoid approach did not have an improved clinical status compared with their preoperative status. The median time to clinical improvement was 3 months (95% CI, 2.15-3.85) for the subxiphoid approach and 6 months (95% CI, 5.54-6.46) for the trans-sternal approach. Univariate results showed that the subxiphoid approach was associated with a faster improvement in clinical status (HR = 1.701, 95% CI, 1.044-2.773, P < 0.05), and age ≦48 was associated with a faster improvement in clinical status (HR = 1.709, 95% CI, 1.044-2.799, P < 0.05). The multivariate model including age ≦48 (HR = 1.837, 95% CI, 1.093-3.086, P = 0.022) and the subxiphoid approach (HR = 1.892, 95% CI, 1.127-3.177, P = 0.016) was significantly associated with a faster improvement in clinical status. Conclusions: In patients with Masaoka stage I and II thymoma who underwent thymectomy, with tumor size less than 5 cm and thymomatous MG, age ≦48 years and the subxiphoid approach were associated with a rapid improvement in clinical status.