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.

Preoperative respiratory muscle training combined with aerobic exercise improves respiratory vital capacity and daily life activity following surgical treatment for myasthenia gravis.

OBJECTIVE: The effects of preoperative respiratory muscle training (RMT) on postoperative complications in patients surgically treated for myasthenia gravis (MG) remain unclear. The present study therefore evaluated the effects of preoperative moderate-to-intense RMT and aerobic exercise, when added to respiratory physiotherapy, on respiratory vital capacity, exercise capacity, and duration of hospital stay in patients with MG. METHODS: Eighty patients with MG scheduled for extended thymectomy were randomly divided into two groups. The 40 subjects in the study group (SG) received preoperative moderate-to-intense RMT and aerobic exercise in addition to respiratory physiotherapy, whereas the 40 subjects in the control group (CG) received only chest physiotherapy. Respiratory vital capacity (as determined by VC, FVC, FEV1, FEV1/FVC, and PEF) and exercise capacity (as determined by the 6-min walk test [6 MWT]) were measured pre- and postoperatively and before discharge. The duration of hospital stay and activity of daily living (ADL) were also determined. RESULTS: Demographic and surgical characteristics, along with preoperative vital capacity and exercise capacity, were similar in the two groups. In the CG, VC (p = 0.001), FVC (p = 0.001), FEV1 (p = 0.002), PEF (p = 0.004), and 6MWT (p = 0.041) were significantly lower postoperatively than preoperatively, whereas the FEV1/FVC ratio did not differ significantly. Postoperative VC (p = 0.012), FVC (p = 0.030), FEV1 (p = 0.014), and PEF (p = 0.035) were significantly higher in the SG than in the CG, although 6MWT results did not differ. ADL on postoperative day 5 was significantly higher in the SG than in the CG (p = 0.001). CONCLUSION: RMT and aerobic exercise can have positive effects on postoperative respiratory vital capacity and daily life activity, and would enhance recovery after surgery in MG patients.

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.

Asiaticoside Suppresses Gastric Cancer Progression and Induces Endoplasmic Reticulum Stress through the miR-635/HMGA1 Axis.

Objective: Gastric cancer is a prevalent malignant tumor with high morbidity and poor prognosis. Asiaticoside (AC) has antitumor effects, while its role in gastric cancer is elusive. Thus, this study investigated the effect of AC on gastric cancer progression. Methods: Cell viability and migration were determined using the CCK-8 and Transwell migration assay. Endoplasmic reticulum stress was detected through measuring the expressions of GRP78, Chop, and hnRNPA1 by Western blot. The luciferase assay confirmed the relationship between miR-635 and High Mobility Group AT-Hook 1 (HMGA1). The effect of AC on tumor growth was evaluated by establishing a xenograft tumor. The survival rate of mice was analyzed by Kaplan-Meier analysis. Results: AC suppressed gastric cancer cell viability and restrained cell migration. AC inhibited the expressions of the cell proliferation marker PCNA and EMT-related marker N-cadherin and increased E-cadherin expression. AC elevated the levels of GRP78 and Chop and suppressed the level of hnRNPA1. In addition, AC restrained gastric cancer proliferation and migration ability and induced endoplasmic reticulum stress by upregulating miR-635 expression. Furthermore, HMGA1 was proven to be a target of miR-635. AC constrained gastric cancer cell proliferation and migration and promoted endoplasmic reticulum stress by regulating HMGA1. Moreover, AC suppressed in vivo tumor growth and improved the survival time of mice. Additionally, AC elevated the expressions of miR-635, E-cadherin, GRP78, and Chop and inhibited Ki-67, HMGA1, N-cadherin, and hnRNPA1 expressions in tumor tissues of mice. Conclusion: AC suppressed gastric cancer progression and induced endoplasmic reticulum stress via the miR-635/HMGA1 axis, providing a valuable drug against gastric cancer.

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.

The Prognostic Impact of Lymph Node Dissection on Primary Tumor Resection for Stage IV Non-Small Cell Lung Cancer: A Population-Based Study.

Objective: Selected patients with stage IV non-small cell lung cancer (NSCLC) who underwent primary tumor resection have witnessed a survival benefit. Whether additional lymph node dissection (LND) would result in a better effect remain unknown. We investigated the prognostic impact of LND on patients with stage IV NSCLC who received primary tumor resection (PTR). Methods: Patients with stage IV NSCLC who underwent PTR were identified from the Surveillance, Epidemiology, and End Results database from 2004 to 2016. Propensity-score matching was performed to minimize the confounding effect, and lung cancer-specific survival (CSS) and overall survival (OS) were compared after matching. Multivariable Cox regression was used to identify prognostic factors and to adjust for covariates in subgroup analysis. The effect of the number of lymph nodes examined on the CSS was evaluated by repeating the Cox analysis in a binary method. Results: A total of 4,114 patients with stage IV NSCLC who receive surgery met our criteria, of which 2,622 (63.73%) underwent LND and 628 patients were identified 1:1 in LND and non-LND groups after matching. Compared with the non-LND group, the LND group had a longer CSS (median: 23 vs. 16 months, p < 0.001) and OS (median: 21 vs. 15 months, p < 0.001). Multivariable regression showed that LND was independently associated with favorable CCS [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.69-0.89, P < 0.001] and OS (HR = 0.79, 95% CI 0.70-0.89, P < 0.001). Subgroup analysis suggested that LND is an independent favorable predictor to survival in the surgical patients who were older age (>60 years old), female, T3-4, N0, and M1a stage and those who underwent sublobar resection. In addition, a statistically significant CCS benefit was associated with an increasing number of lymph nodes examined through 25 lymph nodes. Conclusions: LND with a certain range of lymph nodes number examined was associated with improved survival for patients with stage IV NSCLC who received primary tumor resection. The results may have implications for guidelines on lymph nodes management in selective advanced NSCLC for surgery.

Airflow obstruction, impaired lung function and risk of sudden cardiac death: a prospective cohort study.

BACKGROUND: Growing evidence suggests that compromised lung health may be linked to cardiovascular disease. However, little is known about its association with sudden cardiac death (SCD). OBJECTIVES: We aimed to assess the link between impaired lung function, airflow obstruction and risk of SCD by race and gender in four US communities. METHODS: A total of 14 708 Atherosclerosis Risk in Communities (ARIC) study participants who underwent spirometry and were asked about lung health (1987-1989) were followed. The main outcome was physician-adjudicated SCD. Fine-Gray proportional subdistribution hazard models with Firth's penalised partial likelihood correction were used to estimate the HRs. RESULTS: Over a median follow-up of 25.4 years, 706 (4.8%) subjects experienced SCD. The incidence of SCD was inversely associated with FEV1 in each of the four race and gender groups and across all smoking status categories. After adjusting for multiple measured confounders, HRs of SCD comparing the lowest with the highest quintile of FEV1 were 2.62 (95% CI 1.62 to 4.26) for white males, 1.80 (95% CI 1.03 to 3.15) for white females, 2.07 (95% CI 1.05 to 4.11) for black males and 2.62 (95% CI 1.21 to 5.65) for black females. The above associations were consistently observed among the never smokers. Moderate to very severe airflow obstruction was associated with increased risk of SCD. Addition of FEV1 significantly improved the predictive power for SCD. CONCLUSIONS: Impaired lung function and airflow obstruction were associated with increased risk of SCD in general population. Additional research to elucidate the underlying mechanisms is warranted.

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.

Assessment of TMB, PD-L1, and lymphocyte to monocyte ratio as predictive potential in a phase Ib study of sintilimab in patients with advanced solid tumors.

BACKGROUND: Sintilimab is a humanized monoclonal antibody against the programmed cell death 1 (PD-L1). We aimed to assess the safety and activity of sintilimab monotherapy or in combination with chemotherapy in advanced solid tumors. METHODS: This phase Ib study included six cohorts. Cohort A-C were sintilimab monotherapy settings, and enrolled pretreated patients (2/3 L cohorts). Cohort D-F were treatment-naïve patients (1 L cohorts), and received sintilimab plus different chemotherapies. The primary endpoints were safety and objective response rate (ORR). Exploratory endpoints were potential biomarkers for the prognosis after treatment, such as tumor mutation burden scores (TMB), PD-L1 and lymphocyte-to-monocyte ratio (LMR). RESULTS: The ORR was 14.6% in the 2/3 L cohorts (n=146), and 73.2% in the 1 L cohorts (n=61). The incidence of grade 3-4 adverse events occurred in 55 patients (37.7%) in 2/3 L cohorts, and in 38 (62.3%) in 1 L cohorts. 157 patients had available TMB scores, and in 2/3 L cohorts, patients in the high TMB groups (TMB≥10) showed a longer progression-free survival (PFS) and overall survival (OS) than those in the low TMB groups (TMB<10). No significant differences in PFS and OS were observed across different PD-L1 groups in both 1 L and 2/3 L cohorts. A high LMR was significantly associated with an improved PFS in 1 L cohorts (P=0.022). CONCLUSION: Sintilimab alone or combined with chemotherapy had a tolerable safety profile in solid tumors. The combination therapy showed a favorable activity with advanced non-small cell lung cancer and gastric or esophagogastric junction adenocarcinoma. LMR might be a prognostic factor for the combination regimen in these patients. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02937116. Registered 18 October 2016.

Factors affecting improvement of neurologic status evaluated by Quantitative Myasthenia Gravis Score for patients with thymomatous myasthenia gravis after extended thymectomy.

BACKGROUND: The length of time for clinical improvement of patients with thymomatous myasthenia gravis (MG) after extended thymectomy is not clear. The purpose of this study was to determine the length of time after thymectomy in patients with thymomatous MG to achieve a 3-point reduction of Quantitative Myasthenia Gravis Score (QMGS), and identify variables associated with a failure to achieve the reduction. METHODS: The records of patients with thymomatous MG who underwent extended thymectomy from January 2005 to December 2018 were retrospectively reviewed. The primary end point was a reduction of 3 points of QMGs and the secondary end point was another reduction of 3 points of QMGs. RESULTS: A total of 481 patients were included in the analysis, the mean age of the patients was 41.63 ± 8.55 years, and approximately 60% were male. The median time to achieve a 3 point decrease in QMGS was 6 months, and the median time to achieve another 3 point decrease was 30 months. Multivariable analysis indicated that age ≥ 42 years and Masaoka-Koga stage > I were associated with a lower probability of achieving a 3 point decrease in QMGS (HR = 0.55 and 0.65, respectively). Likewise, multivariable analysis indicated that age ≥ 42 years and Masaoka-Koga stage > I were associated with a lower probability of achieving a second 3 point decrease in QMGS (HR = 0.53 and 0.53, respectively). CONCLUSIONS: In patients with thymomatous MG who receive thymectomy, age ≥ 42 years and Masaoka-Koga stage > I are associated with a worse prognosis and failure to achieve a 3 point decrease in QMGS.

Longitudinal change in lung function and subsequent risks of cardiovascular events: evidence from four prospective cohort studies.

BACKGROUND: Lung function is constantly changing over the life course. Although the relation of cross-sectional lung function measure and adverse outcomes has been reported, data on longitudinal change and subsequent cardiovascular (CV) events risks are scarce. Therefore, this study is to determine the association of longitudinal change in lung function and subsequent cardiovascular risks. METHODS: This study analyzed the data from four prospective cohorts. Subjects with at least two lung function tests were included. We calculated the rate of forced respiratory volume in 1 s (FEV1) and forced vital capacity (FVC) decline for each subject and categorized them into quartiles. The primary outcome was CV events, defined as a composite of coronary heart disease (CHD), chronic heart failure (CHF), stroke, and any CV death. Cox proportional hazards regression and restricted cubic spline models were applied. RESULTS: The final sample comprised 12,899 participants (mean age 48.58 years; 43.61% male). Following an average of 14.79 (10.69) years, 3950 CV events occurred. Compared with the highest FEV1 quartile (Q4), the multivariable HRs for the lowest (Q1), 2nd (Q2), and 3rd quartiles (Q3) were 1.33 (95%CI 1.19, 1.49), 1.30 (1.16, 1.46), and 1.07 (0.95, 1.21), respectively. Likewise, compared with the reference quartile (Q4), the group that experienced a faster decline in FVC had higher HRs for CV events (1.06 [95%CI 0.94-1.20] for Q3, 1.15 [1.02-1.30] for Q2, and 1.28 [1.14-1.44] for Q1). The association remained robust across a series of sensitivity analyses and nearly all subgroups but was more evident in subjects < 60 years. CONCLUSIONS: We observed a monotonic increase in risks of CV events with a faster decline in FEV1 and FVC. These findings emphasize the value of periodic evaluation of lung function and open new opportunities for disease prevention.

Body mass index trajectories during mid to late life and risks of mortality and cardiovascular outcomes: Results from four prospective cohorts.

BACKGROUND: Our understanding of the weight-outcome association mainly comes from single-time body mass index (BMI) measurement. However, data on long-term trajectories of within-person changes in BMI on diverse study outcomes are sparse. Therefore, this study is to determine the associations of individual BMI trajectories and cardiovascular outcomes. METHODS: The present analysis was based on data from 4 large prospective cohorts and restricted to participants aged ≥45 years with at least two BMI measurements. Hazard ratios (HR) and 95% confidence intervals(95%CI) for each outcome according to different BMI trajectories were calculated in Cox regression models. FINDINGS: The final sample comprised 29,311 individuals (mean age 58.31 years, and 77.31% were white), with a median 4 BMI measurements used in this study. During a median follow-up of 21.16 years, there were a total of 10,192 major adverse cardiovascular events (MACE) and 11,589 deaths. A U-shaped relation was seen with all study outcomes. Compared with maintaining stable weight, the multivariate adjusted HR for MACE were 1.53 (95%CI 1.40-1.66), 1.26 (95%CI 1.16-1.37) and 1.08 (95%CI 1.02-1.15) respectively for rapid, moderate and slow weight loss; 1.01 (95%CI 0.95-1.07), 1.13 (95%CI 1.05-1.21) and 1.29 (95%CI 1.20-1.40) respectively for slow, moderate and rapid weight gain. Identical patterns of association were observed for all other outcomes. The development of BMI differed markedly between the outcome-free individuals and those who went on to experience adverse events, generally beginning to diverge 10 years before the occurrence of the events. INTERPRETATION: Our findings may signal an underlying high-risk population and inspire future studies on weight management. FUNDING: National Natural Science Foundation of China, Guangdong Natural Science Foundation.

Characteristics of genomic mutations and signaling pathway alterations in thymic epithelial tumors.

BACKGROUND: To elucidate the mechanisms of thymic epithelial tumor (TET) canceration by characterizing genomic mutations and signaling pathway alterations. METHODS: Primary tumor and blood samples were collected from 21 patients diagnosed with TETs (thymoma and thymic cancer), 15 of whom were screened by nucleic acid extraction and whole exon sequencing. Bioinformatics was used to comprehensively analyze the sequencing data for these samples, including gene mutation information and the difference of tumor mutation burden (TMB) between thymoma and thymic carcinoma groups. We performed signaling pathway and functional enrichment analysis using the WebGestalt 2017 toolkit. RESULTS: ZNF429 (36%) was the gene with the highest mutation frequency in thymic carcinoma. Mutations in BAP1 (14%), ABI1 (7%), BCL9L (7%), and CHEK2 (7%) were exclusively detected in thymic carcinoma, whereas ZNF721 mutations (14%) and PABPC1 (14%) were found exclusively in thymoma. The mean TMB values for thymic carcinoma and thymoma were 0.722 and 0.663 mutations per megabase (Mb), respectively, and these differences were not statistically significant. The ErbB signaling pathway was enriched in the thymoma and intersection groups, and pathways of central carbon metabolism in cancer, longevity regulating and MAPK signaling were only found in the thymoma group, while pathways in cancer (hsa05200) was found in the thymoma and thymic carcinoma groups. CONCLUSIONS: Multiple differences in somatic genes and pathways have been identified. Our findings provide insights into differences between thymoma and thymic carcinoma that could aid in designing personalized clinical therapeutic strategies.

Disease progression and pseudoprogression following partial response with rare gingiva metastasis upon IBI308 (sintilimab) immunotherapy reflects the complexity of metastatic lung cancer: a case report.

The differential diagnosis of progression and pseudoprogression is one difficulty in current immunotherapy. Since the time point and criteria for pseudoprogression diagnosis are not yet unified, current diagnosis and treatment rely on imaging and pathology. Here we report a 57-year-old Chinese male presented solitary left lower lung nodule with enlarged left hilar and mediastinal lymph nodes. Bilateral adrenal nodules and bilateral parietal lobe nodules were identified. The nodules were considered malignant by CT or MRI examinations. The patient was diagnosed left lower peripheral lung cancer with left hilar and mediastinal lymph node metastasis, bilateral adrenal metastasis, and bilateral parietal lobe metastasis. Progression was observed after the first-line pemetrexed + cisplatin (PP) standard chemotherapy. Due to the identification of strong positive PD-L1 expression (90%) in primary tissue immunohistochemistry, second-line IBI308 (sintilimab) immunotherapy was implemented. After the third cycle of immunotherapy, partial response was observed with the left lung lesion and the lung hilus and adrenal metastases, while pseudoprogression was found at the left lung and right hepatic lobe, and rare gingival progression was also identified. Palliative surgery was performed to remove the gingival metastatic lesion. The lesions of the lung, hilar and mediastinal lymph nodes and adrenal gland responded well, but the patient died due to uncontrollable progression of metastatic lesions in the brain. Whole-exome sequencing on gingival metastasis revealed pathogenic mutations in several important driver genes, including TP53, ErbB2, MET and PTEN. This study reported the coexistence of primary lesion response, pseudoprogression and progression in immunotherapy in lung cancer patient with rare gingival metastasis, and provided experience for handling mixed responses in immunotherapy.

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.

Perioperative risk factors for occurrence of myasthenia gravis after thymectomy in patients with thymoma.

OBJECTIVES: The goal of this study was to identify the relationship between clinical characteristics and the occurrence of postoperative myasthenia gravis (PMG) in patients with thymomas and to further identify the relationship between PMG and prognosis. METHODS: Thymoma patients who had surgery at the First Affiliated Hospital of Sun Yat-sen University between July 2004 and July 2016 were reviewed and those who had no previous symptoms of myasthenia gravis were selected for further investigation. In total, 229 patients were included in the study; their clinical characteristics were gathered and analysed. RESULTS: Among the 229 patients, 19 (8.3%) had PMG. The time between the operation and the onset of myasthenia gravis was 134 days on average (range 2-730 days). Patients experiencing PMG showed a lower rate of complete thymoma resection (73.7% vs 91.4%; P = 0.014) and total thymectomy (63.2% vs 82.9%; P = 0.035) compared with those who did not. Univariable and multivariable logistic regression revealed that thymomectomy [odds ratio (OR) 2.81, 95% confidence interval (CI) 1.02-7.77; P = 0.047] and incomplete tumour resection (OR 3.79, 95% CI 1.20-11.98; P = 0.023) were associated with the occurrence of PMG. Multivariable Cox regression showed that the PMG was not related to overall survival (P = 0.087). CONCLUSIONS: This study revealed that incomplete tumour resection and thymomectomy were independent risk factors for PMG in thymoma patients with no previous history of myasthenia gravis.

Early extubation after thymectomy is good for the patients with myasthenia gravis.

OBJECTIVES: Patients with myasthenia gravis (MG) often benefit from thymectomy, but the optimal timing of extubation following thymectomy in these patients remains unknown. This study of MG patients compared the effect of early and late extubation following thymectomy on clinical outcome. METHODS: We performed a study of data from 96 patients with MG who received thymectomy procedures, followed by early (< 6 h) or late (> 6 h) extubation, at our institution between October 2011 and November 2017. Patient clinical and demographic characteristics, preoperative data, and postoperative clinical outcomes were analyzed. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. RESULTS: The patients in the early extubation group (n = 53) and late extubation group (n = 43) had similar preoperative clinical and demographic characteristics. However, the early extubation group had a significantly longer duration of MG (24 months vs. 12 months, P < 0.013) and a lower incidence of reintubation (11.3% vs. 37.2%, P = 0.003). Postoperative pulmonary infection was significantly more common in the late extubation group (39.5% vs. 11.3%, P = 0.001; adjusted odds ratio = 6.94, 95% CI 1.24-38.97). Also, patients in the late extubation group had a longer duration of ICU stay (6.4 ± 4.0 h vs. 4.3 ± 1.8 h; P = 0.003) and had a longer adjusted duration of ICU stay by 0.93 days (95% CI 0.02-1.85). CONCLUSIONS: Our analysis of patients with MG who received thymectomy procedures indicated that early extubation was associated with improved clinical outcomes, in particular with reduced risk of postoperative pulmonary infection and reduced ICU stay.